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Mantyh, Christopher Ritchie

Overview:

Neurogenic inflammation
Ulcerative colitis
Crohn's disease
Neuropeptides
Receptors
Vanilloid receptor
Substance P
Intestinal motility
Colorectal cancer outcomes
Colon cancer
Rectal cancer

Positions:

Professor of Surgery

Surgery, Advanced Oncologic and Gastrointestinal Surgery
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1991

M.D. — University of Wisconsin at Madison

Resident, Surgery

Duke University

Grants:

Prevention of Surgical Site Infection using Statistical Process Control Charts

Administered By
Medicine, Infectious Diseases
AwardedBy
Agency for Healthcare Research and Quality
Role
Co Investigator
Start Date
September 01, 2015
End Date
June 30, 2020

DFA-02 in Patients Undergoing Abdominal Surgery

Administered By
Surgery, Advanced Oncologic and Gastrointestinal Surgery
AwardedBy
Dr. Reddy's Laboratories Ltd.
Role
Principal Investigator
Start Date
March 01, 2014
End Date
November 22, 2016

Using Message Framing to Promote Physical Activity in Colorectal Cancer Survivors

Administered By
Radiation Oncology
AwardedBy
National Institutes of Health
Role
Investigator
Start Date
August 01, 2008
End Date
July 31, 2012

Coherence Imaging for Assessing Colorectal Neoplasia

Administered By
Surgery, Advanced Oncologic and Gastrointestinal Surgery
AwardedBy
National Institutes of Health
Role
Investigator
Start Date
May 24, 2009
End Date
April 30, 2012

Effects of Short Chain Fatty Acids on Colonic Motility

Administered By
Surgery, Surgical Sciences
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
September 01, 2005
End Date
December 31, 2007

Cancer Care Quality Measures: Diagnosis and Treatment of Colorectal Cancer

Administered By
Institutes and Centers
AwardedBy
Agency for Healthcare Research and Quality
Role
Investigator
Start Date
December 01, 2004
End Date
December 31, 2005
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Publications:

Adjuvant Chemotherapy After Preoperative Chemoradiation Improves Survival in Patients With Locally Advanced Rectal Cancer.

Practice guidelines differ in their support of adjuvant chemotherapy use in patients who received preoperative chemoradiation for rectal cancer.The purpose of this study was to evaluate the impact of adjuvant chemotherapy among patients with locally advanced rectal cancer who received neoadjuvant chemoradiation and surgery.This was a retrospective study. Multivariable Cox proportional hazard modeling was used to evaluate the adjusted survival differences.Data were collected from the National Cancer Database.Adults with pathologic stage II and III rectal adenocarcinoma who received neoadjuvant chemoradiation and surgery were included.Overall survival was measured.Among 12,696 patients included, 4023 (32%) received adjuvant chemotherapy. The use of adjuvant chemotherapy increased over the study period from 23% to 36%. Although older age and black race were associated with a lower likelihood of receiving adjuvant chemotherapy, patients with higher education level and stage III disease were more likely to receive adjuvant chemotherapy (all p < 0.05). At 7 years, overall survival was improved among patients who received adjuvant chemotherapy (60% vs. 55%; p < 0.001). After risk adjustment, the use of adjuvant chemotherapy was associated with improved survival (HR = 0.81 (95% CI, 0.72-0.91); p < 0.001). In the subgroup of patients with stage II disease, survival was also improved among patients who received adjuvant chemotherapy (68% vs 58% at 7 y; p < 0.001; HR = 0.70 (95% CI, 0.57-0.87); p = 0.002). Among patients with stage III disease, the use of adjuvant chemotherapy was associated with a smaller but persistent survival benefit (56% vs 51% at 7 y; p = 0.017; HR = 0.85 (95% CI, 0.74-0.98); p = 0.026).The study was limited by its potential for selection bias and inability to compare specific chemotherapy regimens.The use of adjuvant chemotherapy among patients with rectal cancer who received preoperative chemoradiation conferred a survival benefit. This study emphasizes the importance of adjuvant chemotherapy in the management of rectal cancer and advocates for its increased use in the setting of neoadjuvant therapy. See Video Abstract at http://link.lww.com/DCR/A428.

Authors
Sun, Z; Gilmore, B; Adam, MA; Kim, J; Hsu, S-WD; Migaly, J; Mantyh, CR
MLA Citation
Sun, Z, Gilmore, B, Adam, MA, Kim, J, Hsu, S-WD, Migaly, J, and Mantyh, CR. "Adjuvant Chemotherapy After Preoperative Chemoradiation Improves Survival in Patients With Locally Advanced Rectal Cancer." Diseases of the colon and rectum 60.10 (October 2017): 1050-1056.
PMID
28891848
Source
epmc
Published In
Diseases of the Colon and Rectum
Volume
60
Issue
10
Publish Date
2017
Start Page
1050
End Page
1056
DOI
10.1097/dcr.0000000000000907

Resected irradiated rectal cancers: Are twelve lymph nodes really necessary in the era of neoadjuvant therapy?

Our study aims to identify the minimum number of lymph nodes (LN) associated with improved survival in patients who underwent NRT for stage II-III rectal cancer.Adults with clinical stage II and III rectal adenocarcinoma in the National Cancer Data Base were stratified by NRT. Multivariable Cox regression modeling with restricted cubic splines was used to determine the minimum number of LNs associated with improved survival.Of 38,363 patients, 76% received NRT. After adjustment, a LNY≥12 was associated with improved survival among patients receiving NRT (HR 0.79, p < 0.0001) and those without NRT (HR 0.88, p = 0.04). Among patients receiving NRT, factors independently associated with LNY≥12 were younger age, private insurance, low comorbidity score, a recent year of diagnosis, higher T stage and grade, APR resection, and academic institution.A minimum LNY of 12 confers a survival benefit for rectal cancer patients regardless of receiving neoadjuvant radiation therapy.Adults with resected stage II and III rectal adenocarcinoma in the NCDB were stratified by neoadjuvant radiation therapy and analyzed with restricted cubic splines to determine the minimum number of lymph nodes associated with improved survival. A minimum yield of 12 remains essential for a survival benefit in rectal cancer.

Authors
Cox, ML; Adam, MA; Shenoi, MM; Turner, MC; Sun, Z; Mantyh, CR; Migaly, J
MLA Citation
Cox, ML, Adam, MA, Shenoi, MM, Turner, MC, Sun, Z, Mantyh, CR, and Migaly, J. "Resected irradiated rectal cancers: Are twelve lymph nodes really necessary in the era of neoadjuvant therapy?." August 26, 2017.
PMID
28890055
Source
epmc
Published In
The American Journal of Surgery
Publish Date
2017
DOI
10.1016/j.amjsurg.2017.08.014

Skin antisepsis: it's not only what you use, it's the way that you use it

Authors
Casey, AL; Badia, JM; Higgins, A; Korndorffer, J; Mantyh, C; Mimoz, O; Moro, M
MLA Citation
Casey, AL, Badia, JM, Higgins, A, Korndorffer, J, Mantyh, C, Mimoz, O, and Moro, M. "Skin antisepsis: it's not only what you use, it's the way that you use it." Journal of Hospital Infection 96.3 (July 2017): 221-222.
Source
crossref
Published In
Journal of Hospital Infection
Volume
96
Issue
3
Publish Date
2017
Start Page
221
End Page
222
DOI
10.1016/j.jhin.2017.04.019

Association Between Neoadjuvant Chemoradiation and Survival for Patients With Locally Advanced Rectal Cancer.

To examine the overall survival differences of neoadjuvant therapy modalities: no therapy, chemotherapy alone, radiation alone, and chemoradiation in a large cohort of patients with locally advanced rectal cancer.Adults with clinical stage II and III rectal adenocarcinoma were selected from the National Cancer Database and grouped by type of neoadjuvant therapies received: no therapy, chemotherapy only, radiotherapy only, or chemoradiation. Multivariable regression methods were used to compare adjusted differences in perioperative outcomes and overall survival.Among 32978 patients included, 9714 (29.5%) received no neoadjuvant therapy, 890 (2.7%) chemotherapy only, 1170 (3.5%) radiotherapy only, and 21204 (64.3%) chemoradiation. Compared to no therapy, chemotherapy or radiotherapy alone was not associated with any adjusted differences in surgical margin positivity, permanent colostomy rate, or overall survival (all p > 0.05). With adjustment, neoadjuvant chemoradiation vs. no therapy was associated with a lower likelihood of surgical margin positivity (OR 0.74, p < 0.001), decreased rate of permanent colostomy (OR 0.77, p < 0.001), and overall survival (HR 0.79, p < 0.001). When compared to chemotherapy or radiotherapy alone, chemoradiation remain associated with improved overall survival (vs. chemotherapy alone: HR 0.83, p = 0.04; vs. radiotherapy alone: HR 0.83, p < 0.019).Neoadjuvant chemoradiation, not chemotherapy or radiotherapy alone, is important for sphincter preservation, R0 resection, and survival for patients with locally advanced rectal cancer. Despite this finding, one-third of patients in the United States with locally advanced rectal cancer fail to receive stage-appropriate chemoradiation. This article is protected by copyright. All rights reserved.

Authors
Sun, Z; Adam, MA; Kim, J; Turner, MC; Fisher, DA; Choudhury, KR; Czito, BG; Migaly, J; Mantyh, CR
MLA Citation
Sun, Z, Adam, MA, Kim, J, Turner, MC, Fisher, DA, Choudhury, KR, Czito, BG, Migaly, J, and Mantyh, CR. "Association Between Neoadjuvant Chemoradiation and Survival for Patients With Locally Advanced Rectal Cancer." Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland (June 6, 2017).
PMID
28586509
Source
epmc
Published In
Colorectal Disease
Publish Date
2017
DOI
10.1111/codi.13754

The appropriateness of 30-day mortality as a quality metric in colorectal cancer surgery.

Our study compares 30-day vs. 90-day mortality following colorectal cancer surgery (CRS), and examines hospital performance ranking based on this assessment.Mortality rates were compared between 30 vs. 90 days following CRS for patients with stage I-III colorectal cancers from the National Cancer Database (2004-2012). Risk-adjusted hierarchical regression models evaluated hospital performance based on mortality. Hospitals were ranked into top (10%), middle (80%), and lowest (10%) performance groups.Among 185,464 patients, 90-day mortality was nearly double the 30-day mortality (4.4% vs. 2.5%). Following risk adjustment 176 hospitals changed performance ranking: 39% in the top 30-day mortality group changed ranking to the middle group; 37% of hospitals in the lowest 30-day group changed ranking to the middle 90-day group.Evaluation of hospital performance based on 30-day mortality is associated with misclassification for 15% of hospitals. Ninety-day mortality may be a better quality metric in oncologic CRS.

Authors
Adam, MA; Turner, MC; Sun, Z; Kim, J; Ezekian, B; Migaly, J; Mantyh, CR
MLA Citation
Adam, MA, Turner, MC, Sun, Z, Kim, J, Ezekian, B, Migaly, J, and Mantyh, CR. "The appropriateness of 30-day mortality as a quality metric in colorectal cancer surgery." American journal of surgery (June 3, 2017).
PMID
28599835
Source
epmc
Published In
The American Journal of Surgery
Publish Date
2017
DOI
10.1016/j.amjsurg.2017.04.018

Association Between Incomplete Neoadjuvant Radiotherapy and Survival for Patients With Locally Advanced Rectal Cancer.

Failing to complete chemotherapy adversely affects survival in patients with colorectal cancer. However, the effect of incomplete delivery of neoadjuvant radiotherapy is unclear.To determine whether incomplete radiotherapy delivery is associated with worse clinical outcomes and survival.Data on 17 600 patients with stage II to III rectal adenocarcinoma from the 2006-2012 National Cancer Database who received neoadjuvant chemoradiotherapy followed by surgical resection were included. Multivariable regression methods were used to compare resection margin positivity, permanent colostomy rate, 30-day readmission, 90-day mortality, and overall survival between patients who received complete (45.0-50.4 Gy) and incomplete (<45.0 Gy) doses of radiation as preoperative therapy.The primary outcome measure was overall survival; short-term perioperative and oncologic outcomes encompassing margin positivity, permanent ostomy rate, postoperative readmission, and postoperative mortality were also assessed.Among 17 600 patients included, 10 862 were men, with an overall median age of 59 years (range, 51-68 years). Of these, 874 patients (5.0%) received incomplete doses of neoadjuvant radiation. The median radiation dose received among those who did not achieve complete dosing was 34.2 Gy (interquartile range, 19.8-40.0 Gy). Female sex (adjusted odds ratio [OR] 0.69; 95% CI, 0.59-0.81; P < .001) and receiving radiotherapy at a different hospital than the one where surgery was performed (OR, 0.72; 95% CI, 0.62-0.85; P < .001) were independent predictors of failing to achieve complete dosing; private insurance status was predictive of completing radiotherapy (OR, 1.60; 95% CI, 1.16-2.21; P = .004). At 5-year follow-up, overall survival was improved among patients who received a complete course of radiotherapy (3086 [estimated survival probability, 73.2%] vs 133 [63.0%]; P < .001). After adjustment for demographic, clinical, and tumor characteristics, patients receiving a complete vs incomplete radiation dose had a similar resection margin positivity (OR, 0.99; 95% CI, 0.72-1.35; P = .92), permanent colostomy rate (OR, 0.96; 95% CI, 0.70-1.32; P = .81), 30-day readmission rate (OR, 0.92; 95% CI, 0.67-1.27; P = .62), and 90-day mortality (OR, 0.72; 95% CI, 0.33-1.54; P = .41). However, a complete radiation dose had a significantly lower risk of long-term mortality (adjusted hazard ratio, 0.70; 95% CI, 0.59-0.84; P < .001).Achieving a target radiation dose of 45.0 to 50.4 Gy is associated with a survival benefit in patients with locally advanced rectal cancer. Aligning all aspects of multimodal oncology care may increase the probability of completing neoadjuvant therapy.

Authors
Freischlag, K; Sun, Z; Adam, MA; Kim, J; Palta, M; Czito, BG; Migaly, J; Mantyh, CR
MLA Citation
Freischlag, K, Sun, Z, Adam, MA, Kim, J, Palta, M, Czito, BG, Migaly, J, and Mantyh, CR. "Association Between Incomplete Neoadjuvant Radiotherapy and Survival for Patients With Locally Advanced Rectal Cancer." JAMA surgery 152.6 (June 2017): 558-564.
PMID
28273303
Source
epmc
Published In
JAMA Surgery
Volume
152
Issue
6
Publish Date
2017
Start Page
558
End Page
564
DOI
10.1001/jamasurg.2017.0010

How can we effectively address the medical and psychological concerns of survivors of pelvic malignancies?

© 2017, UBM Medica Healthcare Publications. All rights reserved. Sexual and urinary morbidities resulting from treatment of pelvic malignancies are common. Awareness of these complications is critical in order to properly counsel patients regarding potential side effects and to facilitate prompt diagnosis and management.

Authors
Madden-Fuentes, RJ; Koontz, BF; Harrison, MR; George, DJ; Davidson, B; Gilmore, BF; Moul, JW; Mantyh, C; Peterson, AC
MLA Citation
Madden-Fuentes, RJ, Koontz, BF, Harrison, MR, George, DJ, Davidson, B, Gilmore, BF, Moul, JW, Mantyh, C, and Peterson, AC. "How can we effectively address the medical and psychological concerns of survivors of pelvic malignancies?." ONCOLOGY (United States) 31.4 (April 15, 2017): 268-294. (Review)
Source
scopus
Published In
Oncology
Volume
31
Issue
4
Publish Date
2017
Start Page
268
End Page
294

Insurance Status, Not Race, is Associated With Use of Minimally Invasive Surgical Approach for Rectal Cancer.

To determine the impact of race and insurance on use of minimally invasive (MIS) compared with open techniques for rectal cancer in the United States.Race and socioeconomic status have been implicated in disparities of rectal cancer treatment.Adults undergoing MIS (laparoscopic or robotic) or open rectal resections for stage I to III rectal adenocarcinoma were included from the National Cancer Database (2010-2012). Multivariate analyses were employed to examine the adjusted association of race and insurance with use of MIS versus open surgery.Among 23,274 patients, 39% underwent MIS and 61% open surgery. Overall, 86% were white, 8% black, and 3% Asian. Factors associated with use of open versus MIS were black race, Medicare/Medicaid insurance, and lack of insurance. However, after adjustment for patient demographic, clinical, and treatment characteristics, black race was not associated with use of MIS versus open surgery [odds ratio [OR] 0.90, P = 0.07). Compared with privately insured patients, uninsured patients (OR 0.52, P < 0.01) and those with Medicare/Medicaid (OR 0.79, P < 0.01) were less likely to receive minimally invasive resections. Lack of insurance was significantly associated with less use of MIS in black (OR 0.59, P = 0.02) or white patients (OR 0.51, P < 0.01). However, among uninsured patients, black race was not associated with lower use of MIS (OR 0.96, P = 0.59).Insurance status, not race, is associated with utilization of minimally invasive techniques for oncologic rectal resections. Due to the short-term benefits and cost-effectiveness of minimally invasive techniques, hospitals may need to improve access to these techniques, especially for uninsured patients.

Authors
Turner, M; Adam, MA; Sun, Z; Kim, J; Ezekian, B; Yerokun, B; Mantyh, C; Migaly, J
MLA Citation
Turner, M, Adam, MA, Sun, Z, Kim, J, Ezekian, B, Yerokun, B, Mantyh, C, and Migaly, J. "Insurance Status, Not Race, is Associated With Use of Minimally Invasive Surgical Approach for Rectal Cancer." Annals of surgery 265.4 (April 2017): 774-781.
PMID
27163956
Source
epmc
Published In
Annals of Surgery
Volume
265
Issue
4
Publish Date
2017
Start Page
774
End Page
781
DOI
10.1097/sla.0000000000001781

Hand-Assisted Laparoscopic Colectomy Improves Perioperative Outcomes Without Increasing Operative Time Compared to the Open Approach: a National Analysis of 8791 Patients.

Hand-assisted laparoscopic surgery (HALS) is often used in procedures too complex for completely minimally invasive approaches. However, there are concerns for whether this hybrid approach abrogates perioperative benefits of the completely minimally invasive technique.We queried the 2012-2013 National Surgery Quality Improvement Program for adults undergoing elective HALS or open colectomy (OC). After propensity matching, short-term outcomes were compared. Subset analysis was performed for segmental resections. Multivariate analysis was used to determine predictors of utilizing either approach.This query included 8791 patients (OC 2707, HALS 6084). Predictors of HALS included male sex (OR 1.17, p = 0.006), increasing BMI (OR 1.01, p = 0.02), benign indication (OR 1.48, p < 0.001), and total abdominal colectomy (OR 10.39, p < 0.001). Younger age, black race, ASA class ≥3, inflammatory bowel disease, and low pelvic anastomosis were predictive of OC (all p < 0.05). HALS demonstrated reduced overall complications (p < 0.001), wound complications (p < 0.001), anastomotic leak (p = 0.014), transfusion (p < 0.001), postoperative ileus (p < 0.001), length of stay (p < 0.001), and readmission (p < 0.001) without increased operative time. For segmental resection, HALS demonstrated reduced overall complications, wound complications, respiratory complications, postoperative ileus, anastomotic leak, transfusion, length of stay, and readmissions (all p < 0.05).Compared to OC, HALS demonstrates improved perioperative outcomes without increased operative time.

Authors
Leraas, HJ; Ong, CT; Sun, Z; Adam, MA; Kim, J; Gilmore, BF; Ezekian, B; Nag, US; Mantyh, CR; Migaly, J
MLA Citation
Leraas, HJ, Ong, CT, Sun, Z, Adam, MA, Kim, J, Gilmore, BF, Ezekian, B, Nag, US, Mantyh, CR, and Migaly, J. "Hand-Assisted Laparoscopic Colectomy Improves Perioperative Outcomes Without Increasing Operative Time Compared to the Open Approach: a National Analysis of 8791 Patients." Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract 21.4 (April 2017): 684-691.
PMID
28083836
Source
epmc
Published In
Journal of Gastrointestinal Surgery
Volume
21
Issue
4
Publish Date
2017
Start Page
684
End Page
691
DOI
10.1007/s11605-016-3350-5

Determining the Optimal Quantitative Threshold for Preoperative Albumin Level Before Elective Colorectal Surgery.

Hypoalbuminemia is associated with adverse surgical outcomes. A minimum threshold and the impact of incrementally decreasing albumin remain undefined for colorectal surgery patients.The 2011-2013 National Surgical Quality Improvement Program (NSQIP) dataset was queried for patients undergoing elective colorectal surgery. Multivariable regression analyses with restricted cubic splines (RCS) were used to examine the adjusted association between preoperative serum albumin level and the incidence of complications and to establish an optimal threshold. RCS allows for flexible evaluation in multivariable models without having to assume a specific relationship a priori.Sixteen thousand one hundred forty-five patients met study criteria. RCS analysis demonstrated an inflection point at serum albumin level of 3.9 mg/dL. Patients with preoperative albumin <3.9 mg/dL vs. albumin ≥3.9 mg/dL had a higher likelihood of experiencing a major complication (odds ratio (OR) = 1.18, confidence interval (CI) 1.07-1.30, p = 0.0007) or any complications (OR 1.18, CI 1.08-1.29, p = 0.0002,) and had a lengthened hospital stay (p < 0.001).This study objectively determines that a threshold preoperative serum albumin of ≥3.9 mg/dL is associated with improved outcomes in elective colorectal surgery patients. Each 0.5 mg/dL decrease in albumin was progressively associated with increased risk for complications. Identifying a minimum albumin threshold has implications in perioperative optimization of patients undergoing colorectal surgery.

Authors
Bendersky, V; Sun, Z; Adam, MA; Rushing, C; Kim, J; Youngwirth, L; Turner, M; Migaly, J; Mantyh, CR
MLA Citation
Bendersky, V, Sun, Z, Adam, MA, Rushing, C, Kim, J, Youngwirth, L, Turner, M, Migaly, J, and Mantyh, CR. "Determining the Optimal Quantitative Threshold for Preoperative Albumin Level Before Elective Colorectal Surgery." Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract 21.4 (April 2017): 692-699.
PMID
28138809
Source
epmc
Published In
Journal of Gastrointestinal Surgery
Volume
21
Issue
4
Publish Date
2017
Start Page
692
End Page
699
DOI
10.1007/s11605-017-3370-9

Minimizing hair dispersal: Is this an opportunity for improvement in health care-acquired infection prevention?

We performed a study to understand common practices in surgical site hair removal and barriers to guideline compliance in surgical site hair removal. We found most health care providers in the United States do not remove hair outside of the operating room. Our findings reveal minimizing hair dispersal in the operating room, including improved and innovative ways for collecting clipped loose hair, is a significant area for improvement in surgical quality and health care-acquired infection prevention.

Authors
Mantyh, CR; Xi, H; Pearson, L; Perl, TM
MLA Citation
Mantyh, CR, Xi, H, Pearson, L, and Perl, TM. "Minimizing hair dispersal: Is this an opportunity for improvement in health care-acquired infection prevention?." American journal of infection control 45.3 (March 2017): 308-310.
PMID
27814925
Source
epmc
Published In
AJIC -- American Journal of Infection Control
Volume
45
Issue
3
Publish Date
2017
Start Page
308
End Page
310
DOI
10.1016/j.ajic.2016.09.001

V-Y fasciocutaneous flap closure technique is a safe and efficacious alternative to primary closure of the perineal wound following abdominoperineal resection.

The aim of this study was to compare wound complications from V-Y flap vs primary closure in the setting of abdominoperineal resection.This was a single institution retrospective review (1999-2014). The main outcome measures were any wound complication, hospital length of stay, and unplanned readmissions.Among 80 patients included, 21 (26%) received reconstruction with V-Y flap. Compared with those who received primary closure, patients who underwent V-Y flap reconstruction had lower rates of overall wound complications (14.3% vs 64%, P = .002), superficial surgical site infection (6% vs 32%, P = .05), and wound dehiscence (4.5% vs 14%, P = .251 statistical significance not met).Reconstruction of perineal defect following abdominoperineal resection using a V-Y fasciocutaneous flap is a safe and efficacious alternative to traditional simple primary closure and is associated with reduced postoperative morbidity. Further comparative effectiveness studies should be undertaken to evaluate long-term and quality-of-life outcomes.

Authors
Kokosis, G; Sun, Z; Avashia, YJ; Adam, MA; Levinson, H; Erdmann, D; Mantyh, CR; Migaly, J
MLA Citation
Kokosis, G, Sun, Z, Avashia, YJ, Adam, MA, Levinson, H, Erdmann, D, Mantyh, CR, and Migaly, J. "V-Y fasciocutaneous flap closure technique is a safe and efficacious alternative to primary closure of the perineal wound following abdominoperineal resection." American journal of surgery 213.2 (February 2017): 371-376.
PMID
27769545
Source
epmc
Published In
The American Journal of Surgery
Volume
213
Issue
2
Publish Date
2017
Start Page
371
End Page
376
DOI
10.1016/j.amjsurg.2016.04.018

Response to Letter: Comment on "Insurance Status, Not Race Is Associated With Use of Minimally Invasive Surgical Approach for Rectal Cancer".

Authors
Turner, MC; Adam, MA; Sun, Z; Kim, J; Ezekian, B; Yerokun, BA; Mantyh, CR; Migaly, J
MLA Citation
Turner, MC, Adam, MA, Sun, Z, Kim, J, Ezekian, B, Yerokun, BA, Mantyh, CR, and Migaly, J. "Response to Letter: Comment on "Insurance Status, Not Race Is Associated With Use of Minimally Invasive Surgical Approach for Rectal Cancer"." Annals of surgery (February 2017).
PMID
28221165
Source
epmc
Published In
Annals of Surgery
Publish Date
2017
DOI
10.1097/sla.0000000000001974

Intensity-Modulated Radiation Therapy Is Not Associated with Perioperative or Survival Benefit over 3D-Conformal Radiotherapy for Rectal Cancer.

The use of intensity-modulated radiation therapy (IMRT) in rectal cancer has steadily increased over traditional 3D conformal radiotherapy (3D-CRT) due to perceived benefit of delivering higher treatment doses while minimizing exposure to surrounding tissues. However, IMRT is technically challenging and costly, and its effects on rectal cancer outcomes remain unclear.Adults with clinical stage II and III rectal adenocarcinoma who underwent neoadjuvant chemoradiotherapy with 45-54 Gy of radiation and surgery were included from the 2006-2013 National Cancer Data Base. Patients were grouped based the modality of radiation received: IMRT or 3D-CRT. Multivariable regression modeling adjusting for demographic, clinical, and treatment characteristics was used to examine the impact of IMRT vs. 3D-CRT on pathologic downstaging, resection margin positivity, sphincter loss surgery, 30-day unplanned readmission and mortality after surgery, and overall survival.Among 7386 patients included, 3330 (45 %) received IMRT and 4056 (55 %) received 3D-CRT. While the mean radiation dose delivered was higher with IMRT (4735 vs. 4608 cGy, p < 0.001), it was associated with higher risks of positive margins (adjusted odds ratio (OR) 1.57; p < 0.001) and sphincter loss surgery (OR 1.32; p < 0.001). There were no differences between IMRT and 3D-CRT in the likelihood of pathologic downstaging (OR 0.89, p = 0.051), unplanned readmission (OR 0.79; p = 0.07), or 30-day mortality (OR 0.61; p = 0.31) after surgery. Additionally, there were no differences in overall survival at 8 years (IMRT vs. 3D-CRT: 64 vs. 64 %; adjusted hazard ratio 1.06, p = 0.47).IMRT is associated with worse local tumor control without any long-term survival benefit for patients with locally advanced rectal cancer. Given the lack of significant advantage and the higher cost of IMRT, caution should be exercised when using IMRT instead of traditional 3D-CRT for rectal cancer.

Authors
Sun, Z; Adam, MA; Kim, J; Czito, B; Mantyh, C; Migaly, J
MLA Citation
Sun, Z, Adam, MA, Kim, J, Czito, B, Mantyh, C, and Migaly, J. "Intensity-Modulated Radiation Therapy Is Not Associated with Perioperative or Survival Benefit over 3D-Conformal Radiotherapy for Rectal Cancer." Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract 21.1 (January 2017): 106-111.
PMID
27510332
Source
epmc
Published In
Journal of Gastrointestinal Surgery
Volume
21
Issue
1
Publish Date
2017
Start Page
106
End Page
111
DOI
10.1007/s11605-016-3242-8

Intraoperative Frontal Alpha-Band Power Correlates with Preoperative Neurocognitive Function in Older Adults.

Each year over 16 million older Americans undergo general anesthesia for surgery, and up to 40% develop postoperative delirium and/or cognitive dysfunction (POCD). Delirium and POCD are each associated with decreased quality of life, early retirement, increased 1-year mortality, and long-term cognitive decline. Multiple investigators have thus suggested that anesthesia and surgery place severe stress on the aging brain, and that patients with less ability to withstand this stress will be at increased risk for developing postoperative delirium and POCD. Delirium and POCD risk are increased in patients with lower preoperative cognitive function, yet preoperative cognitive function is not routinely assessed, and no intraoperative physiological predictors have been found that correlate with lower preoperative cognitive function. Since general anesthesia causes alpha-band (8-12 Hz) electroencephalogram (EEG) power to decrease occipitally and increase frontally (known as "anteriorization"), and anesthetic-induced frontal alpha power is reduced in older adults, we hypothesized that lower intraoperative frontal alpha power might correlate with lower preoperative cognitive function. Here, we provide evidence that such a correlation exists, suggesting that lower intraoperative frontal alpha power could be used as a physiological marker to identify older adults with lower preoperative cognitive function. Lower intraoperative frontal alpha power could thus be used to target these at-risk patients for possible therapeutic interventions to help prevent postoperative delirium and POCD, or for increased postoperative monitoring and follow-up. More generally, these results suggest that understanding interindividual differences in how the brain responds to anesthetic drugs can be used as a probe of neurocognitive function (and dysfunction), and might be a useful measure of neurocognitive function in older adults.

Authors
Giattino, CM; Gardner, JE; Sbahi, FM; Roberts, KC; Cooter, M; Moretti, E; Browndyke, JN; Mathew, JP; Woldorff, MG; Berger, M; MADCO-PC Investigators,
MLA Citation
Giattino, CM, Gardner, JE, Sbahi, FM, Roberts, KC, Cooter, M, Moretti, E, Browndyke, JN, Mathew, JP, Woldorff, MG, Berger, M, and MADCO-PC Investigators, . "Intraoperative Frontal Alpha-Band Power Correlates with Preoperative Neurocognitive Function in Older Adults." Frontiers in systems neuroscience 11 (January 2017): 24-.
Website
http://hdl.handle.net/10161/14971
PMID
28533746
Source
epmc
Published In
Frontiers in Systems Neuroscience
Volume
11
Publish Date
2017
Start Page
24
DOI
10.3389/fnsys.2017.00024

Hand-Assisted Laparoscopic Versus Standard Laparoscopic Colectomy: Are Outcomes and Operative Time Different?

HAL colectomy is a technique perceived to provide the benefits of laparoscopic surgery while improving tactile feedback and operative time. Published data are largely limited to small, single-institution studies.The 2012-2013 National Surgical Quality Improvement Program Participant Data Use File was queried for patients undergoing elective SL or HAL colectomy. Patients underwent 1:1 propensity matching and had outcomes compared. An additional subgroup analysis was performed for patients undergoing segmental resections only.13,949 patients were identified, of whom 6084 (43.6 %) underwent HAL colectomy. Patients undergoing HAL versus SL colectomy had higher rates of postoperative ileus (8.7 vs. 6.3 %, p < 0.001), wound complication (8.8 vs. 6.8 %, p = 0.006), and 30-day readmission (7.5 vs. 6.0 %, p = 0.002), without any differences in operative time (156 vs. 157 min, p = 0.713). Amongst segmental colectomies, HAL remained associated with higher rates of wound complications (8.6 vs. 6.5 %, p = 0.016), postoperative ileus (8.9 vs. 6.3 %, p < 0.001), and 30-day readmission (7.1 vs. 5.9 %, p = 0.041) with no difference in operative time between HAL and SL (145 vs. 145 min, p = 0.334).Use of HAL colectomy is associated with increased risk of wound complications, postoperative ileus, and readmissions. Importantly, this technique is not associated with any decrease in operative time.

Authors
Gilmore, BF; Sun, Z; Adam, M; Kim, J; Ezekian, B; Ong, C; Migaly, J; Mantyh, CR
MLA Citation
Gilmore, BF, Sun, Z, Adam, M, Kim, J, Ezekian, B, Ong, C, Migaly, J, and Mantyh, CR. "Hand-Assisted Laparoscopic Versus Standard Laparoscopic Colectomy: Are Outcomes and Operative Time Different?." Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract 20.11 (November 2016): 1854-1860.
PMID
27456018
Source
epmc
Published In
Journal of Gastrointestinal Surgery
Volume
20
Issue
11
Publish Date
2016
Start Page
1854
End Page
1860
DOI
10.1007/s11605-016-3206-z

Message Framing and Physical Activity Promotion in Colorectal Cancer Survivors.

To test effects of gain-framed versus loss-framed mailed brochures on increasing physical activity (PA) among colorectal cancer (CRC) survivors.
.Randomized trial with repeated measures at baseline, 1 month, and 12 months postintervention.
.Mail recruitment from tumor registries.
.148 inactive CRC survivors who had completed primary therapy. 
.PA and constructs from the Theory of Planned Behavior (TPB) were assessed at baseline, 1 month, and 12 months. Participants were randomized to receive pamphlets describing PA benefits (gain framed) or disadvantages of not being physically active (loss framed). Baseline characteristics were compared using descriptive statistics. Repeated measures linear models were used to test PA changes.
.Minutes of PA and TPB constructs.
.Significant PA increases were observed in both study arms. Results did not differ by message frame. At one month, about 25% of previously inactive participants increased activity to national recommendations. Those who increased PA compared to those who did not had higher baseline scores on subjective norms, perceived behavioral control, and PA intentions. 
.Independent of message framing, mailed brochures are highly effective in producing within-subject short- and long-term increases in PA.
.CRC survivors may increase short- and long-term levels of PA by receiving inexpensive print brochures.

Authors
Hirschey, R; Lipkus, I; Jones, L; Mantyh, C; Sloane, R; Demark-Wahnefried, W
MLA Citation
Hirschey, R, Lipkus, I, Jones, L, Mantyh, C, Sloane, R, and Demark-Wahnefried, W. "Message Framing and Physical Activity Promotion in Colorectal Cancer Survivors." Oncology nursing forum 43.6 (November 2016): 697-705.
PMID
27768135
Source
epmc
Published In
Oncology Nursing Forum
Volume
43
Issue
6
Publish Date
2016
Start Page
697
End Page
705
DOI
10.1188/16.onf.43-06ap

Robotic-Assisted Versus Laparoscopic Colectomy Results in Increased Operative Time Without Improved Perioperative Outcomes.

Interest in robotic technology is burgeoning within the field of colorectal surgery. However, benefits of robotic-assisted colectomy (RAC) compared with laparoscopic colectomy (LC) remain ambiguous.Patients who underwent minimally invasive colectomy during 2012-2013 were identified from the National Surgical Quality Improvement Program (NSQIP) database. Short-term perioperative outcomes were compared between 1:1 propensity-matched groups. A subset analysis was performed among patients who underwent segmental resections.Among the 15,976 patients included, 498 (3.1 %) colectomies were performed with robotic assistance. After matching for demographic, clinical, and treatment characteristics, there were no differences between RAC and LC in complications such as wound infection, urinary tract infection, cardiopulmonary or thromboembolic events, renal insufficiency, anastomotic leaks, transfusions, readmissions, or 30-day mortality (all p > 0.05). However, operative time was markedly higher for RAC (196 vs. 166 min, p < 0.001). Among segmental resections, operative time remained significantly longer for RAC (190 vs. 153 min, p < 0.001) without differences in perioperative outcomes (all p > 0.05).In this early experience, RAC resulted in similar perioperative outcomes when compared to LC but was associated with longer operative time. Given the focus on value-based healthcare, utilizing RAC in straightforward colectomies may not be financially justifiable at this stage of adoption.

Authors
Ezekian, B; Sun, Z; Adam, MA; Kim, J; Turner, MC; Gilmore, BF; Ong, CT; Mantyh, CR; Migaly, J
MLA Citation
Ezekian, B, Sun, Z, Adam, MA, Kim, J, Turner, MC, Gilmore, BF, Ong, CT, Mantyh, CR, and Migaly, J. "Robotic-Assisted Versus Laparoscopic Colectomy Results in Increased Operative Time Without Improved Perioperative Outcomes." Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract 20.8 (August 2016): 1503-1510.
PMID
26966028
Source
epmc
Published In
Journal of Gastrointestinal Surgery
Volume
20
Issue
8
Publish Date
2016
Start Page
1503
End Page
1510
DOI
10.1007/s11605-016-3124-0

Alvimopan Provides Additional Improvement in Outcomes and Cost Savings in Enhanced Recovery Colorectal Surgery.

To examine the impact of alvimopan on outcomes and costs in a rigorous enhanced recovery colorectal surgery protocol.Postoperative ileus remains a major source of morbidity and costs in colorectal surgery. Alvimopan has been shown to reduce incidence of postoperative ileus in enhanced recovery colorectal surgery; however, data are equivocal regarding its benefit in reducing length of stay and costs.Patients undergoing major elective enhanced recovery colorectal surgery were identified from a prospectively-collected database (2010-2013). Multivariable analyses were employed to compare outcomes and hospital costs among patients who had alvimopan versus no alvimopan by adjusting for demographic, clinical, and treatment characteristics.A total of 660 patients were included; 197 patients received alvimopan and 463 patients had no alvimopan. In unadjusted analysis, the alvimopan group had a faster return of bowel function, shorter length of stay, and lower rates of ileus, Foley re-insertion, and urinary tract infection (all P < 0.01). After adjustment, alvimopan was associated with a faster return of bowel function by 0.6 day (P = 0.0006), and lower incidence of postoperative ileus (odds ratio 0.23, P = 0.0002). With adjustment, alvimopan was associated with a shorter length of stay by 1.6 days (P = 0.002), and a hospital cost savings of $1492 per patient (P = 0.01).Alvimopan administration as an element of enhanced recovery colorectal surgery is associated with faster return of bowel function, lower incidence of postoperative ileus, shorter hospitalization, and a significant cost savings. These results suggest that alvimopan is cost-effective in the setting of enhanced recovery colorectal surgery protocols, and should therefore be considered in these programs.

Authors
Adam, MA; Lee, LM; Kim, J; Shenoi, M; Mallipeddi, M; Aziz, H; Stinnett, S; Sun, Z; Mantyh, CR; Thacker, JKM
MLA Citation
Adam, MA, Lee, LM, Kim, J, Shenoi, M, Mallipeddi, M, Aziz, H, Stinnett, S, Sun, Z, Mantyh, CR, and Thacker, JKM. "Alvimopan Provides Additional Improvement in Outcomes and Cost Savings in Enhanced Recovery Colorectal Surgery." July 2016.
PMID
26501697
Source
epmc
Published In
Annals of Surgery
Volume
264
Issue
1
Publish Date
2016
Start Page
141
End Page
146
DOI
10.1097/sla.0000000000001428

Alvimopan Provides Additional Improvement in Outcomes and Cost Savings in Enhanced Recovery Colorectal Surgery

Authors
Adam, MA; Lee, LM; Kim, J; Shenoi, M; Mallipeddi, M; Aziz, H; Stinnett, S; Sun, Z; Mantyh, CR; Thacker, JKM
MLA Citation
Adam, MA, Lee, LM, Kim, J, Shenoi, M, Mallipeddi, M, Aziz, H, Stinnett, S, Sun, Z, Mantyh, CR, and Thacker, JKM. "Alvimopan Provides Additional Improvement in Outcomes and Cost Savings in Enhanced Recovery Colorectal Surgery." ANNALS OF SURGERY 264.1 (July 2016): 141-146.
Source
wos-lite
Published In
Annals of Surgery
Volume
264
Issue
1
Publish Date
2016
Start Page
141
End Page
146
DOI
10.1097/SLA.0000000000001428

Minimally Invasive Versus Open Low Anterior Resection: Equivalent Survival in a National Analysis of 14,033 Patients With Rectal Cancer.

To examine survival of patients who underwent minimally invasive versus open low anterior resection (LAR) for rectal cancer.Utilization of laparoscopic and robotic LAR for rectal cancer has steadily increased. Short-term outcomes between these techniques and open surgery have shown equivalent results; however, survival outcomes are unknown.Adults from the National Cancer Data Base undergoing LAR for rectal adenocarcinoma were identified. Patients were stratified by intent-to-treat into open (OLAR) or minimally invasive LAR (MI-LAR). Multivariable modeling was used to compare short-term outcomes and survival between MI-LAR and OLAR and between laparoscopic (LLAR) and robotic LAR (RLAR).Among 14,033 patients included, 57.8% underwent OLAR and 42.2% MI-LAR. After adjustment, MI-LAR was associated with shorter length of stay (P < 0.001), but similar rates of positive margins, 30-day readmission, 30-day mortality, and use of adjuvant therapies (all P > 0.05). At 36 months, there was no difference in adjusted risk of mortality between MI-LAR and OLAR (hazard ratio [HR] 0.88, P = 0.089). In a subgroup analysis of LLAR versus RLAR, there were no differences in lymph node harvest, margin positivity, length of stay, readmission rate, 30-day mortality, or overall survival after adjustment (all P > 0.05).Minimally invasive LAR for rectal cancer is associated with similar overall survival with the benefit of shorter hospitalization. Although the conversion rate is lower, robotic LAR is not associated with superior oncologic outcomes compared to laparoscopic LAR. Our findings support the ongoing adoption of minimally invasive techniques for rectal adenocarcinoma.

Authors
Sun, Z; Kim, J; Adam, MA; Nussbaum, DP; Speicher, PJ; Mantyh, CR; Migaly, J
MLA Citation
Sun, Z, Kim, J, Adam, MA, Nussbaum, DP, Speicher, PJ, Mantyh, CR, and Migaly, J. "Minimally Invasive Versus Open Low Anterior Resection: Equivalent Survival in a National Analysis of 14,033 Patients With Rectal Cancer." Annals of surgery 263.6 (June 2016): 1152-1158.
PMID
26501702
Source
epmc
Published In
Annals of Surgery
Volume
263
Issue
6
Publish Date
2016
Start Page
1152
End Page
1158
DOI
10.1097/sla.0000000000001388

Urinary Dysfunction in the Rectal Cancer Survivor

Authors
Gilmore, B; Ezekian, B; Sun, Z; Peterson, A; Mantyh, C
MLA Citation
Gilmore, B, Ezekian, B, Sun, Z, Peterson, A, and Mantyh, C. "Urinary Dysfunction in the Rectal Cancer Survivor." Current Bladder Dysfunction Reports 11.2 (June 2016): 105-112.
Source
crossref
Published In
Current Bladder Dysfunction Reports
Volume
11
Issue
2
Publish Date
2016
Start Page
105
End Page
112
DOI
10.1007/s11884-016-0357-4

Does Conversion in Laparoscopic Colectomy Portend an Inferior Oncologic Outcome? Results from 104,400 Patients.

Limited data exist regarding the effect of conversion from laparoscopic to open colectomy on perioperative and oncologic outcomes in colon cancer.The National Cancer Data Base was used to identify patients who underwent colectomy for non-metastatic colon cancer (2010-2012). Patients were stratified into three groups: laparoscopic/robotic-assisted colectomy (MIC), converted colectomy (CC), and open colectomy (OC). Multivariable modeling was applied to compare outcomes from CC and MIC to OC while adjusting for patient, clinical, and tumor characteristics.Of 104,400 patients, 40,328 (38.6 %) underwent MIC, 57,928 (55.5 %) OC, and 6144 (5.9 %) CC. After adjustment, the rate of positive surgical margins was not significantly different between CC and OC (p = 0.44). However, with adjustment, CC versus OC was associated with shorter hospital length of stay (4 % decrease, 95 % CI 2-5 %, p < 0.0001) and lower odds of 30-day mortality (OR 0.77, 95 % CI 0.64-0.94, p = 0.0112). Adjusted overall survival was similar between CC and OC (p = 0.34).Conversion from laparoscopic to open colectomy was not associated with compromised oncologic outcomes, while maintaining improved short-term outcomes despite being attempted in only 45 % of patients. This data suggests that utilization of laparoscopic colectomy should be attempted for patients with colon cancer.

Authors
Yerokun, BA; Adam, MA; Sun, Z; Kim, J; Sprinkle, S; Migaly, J; Mantyh, CR
MLA Citation
Yerokun, BA, Adam, MA, Sun, Z, Kim, J, Sprinkle, S, Migaly, J, and Mantyh, CR. "Does Conversion in Laparoscopic Colectomy Portend an Inferior Oncologic Outcome? Results from 104,400 Patients." Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract 20.5 (May 2016): 1042-1048.
PMID
26768006
Source
epmc
Published In
Journal of Gastrointestinal Surgery
Volume
20
Issue
5
Publish Date
2016
Start Page
1042
End Page
1048
DOI
10.1007/s11605-016-3073-7

Optimal Timing to Surgery after Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer.

Neoadjuvant chemoradiotherapy (nCRT) has demonstrated proven benefit in tumor regression and improved long-term local control for patients with locally advanced rectal cancer. However, precise analysis of the optimal waiting time that maximizes oncologic benefits of nCRT has not been established.The 2006-2012 National Cancer Data Base was queried for patients with stage II and III rectal adenocarcinoma who underwent nCRT followed by surgical resection. Time to surgery was defined as the difference between last date of radiotherapy and date of surgery. Primary study endpoints included resection margin positivity and pathologic downstaging. Multivariable regression modeling with restricted cubic splines was used to evaluate the adjusted association between time to surgery and our study endpoints, and to establish an optimal time threshold for surgery.A total of 11,760 patients were included. Median time to surgery was 53 days (interquartile range [IQR] 43 to 63 days). After adjusting for patient demographic, clinical, tumor, and treatment characteristics, our model determined an inflection point at 56 days after end of radiotherapy associated with the highest likelihood of complete resection and pathologic downstaging. With adjustment, the risk of margin positivity was increased in those who underwent surgery after 56 days from end of radiotherapy (odds ratio [OR] 1.40, 95% CI 1.21 to 1.61, p < 0.001). The likelihood of downstaging was increasing up to 56 days after radiotherapy (≥56 days vs <56 days, OR 1.2, 95% CI 1.02 to 1.23, p = 0.01).This study objectively determined the optimal time for surgery after completion of nCRT for rectal cancer based on completeness of resection and tumor downstaging. Eight weeks appears to be the critical threshold for optimal tumor response.

Authors
Sun, Z; Adam, MA; Kim, J; Shenoi, M; Migaly, J; Mantyh, CR
MLA Citation
Sun, Z, Adam, MA, Kim, J, Shenoi, M, Migaly, J, and Mantyh, CR. "Optimal Timing to Surgery after Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer." Journal of the American College of Surgeons 222.4 (April 2016): 367-374.
PMID
26897480
Source
epmc
Published In
Journal of The American College of Surgeons
Volume
222
Issue
4
Publish Date
2016
Start Page
367
End Page
374
DOI
10.1016/j.jamcollsurg.2015.12.017

Surgical Resection of the Primary Tumor in Stage IV Colorectal Cancer Without Metastasectomy is Associated With Improved Overall Survival Compared With Chemotherapy/Radiation Therapy Alone.

Controversy exists over whether resection of the primary tumor in stage IV colorectal cancer with inoperable metastases improves patient outcomes.The purpose of this study was to evaluate whether resection of the primary tumor without metastasectomy in patients with stage IV colorectal cancer is associated with improved overall survival compared with patients undergoing chemotherapy and/or radiation therapy alone.This was a retrospective review of a multi-institutional dataset.This study was conducted in all participating commission on cancer (CoC)-accredited facilities.The 2003-2006 National Cancer Data Base was reviewed to identify patients with stage IV adenocarcinoma of the colon or rectum who underwent palliative treatment without curative intent, either in the form of surgical resection of the primary tumor without metastasectomy consisting of a colectomy or rectal resection with or without chemotherapy and/or radiation or chemotherapy and/or radiation alone.Groups were compared for baseline characteristics. Overall survival was compared using Kaplan-Meier analysis before and after propensity matching with a 1:1 nearest-neighbor algorithm.Of the 1446 patients included in the analysis, 231 (16%) underwent surgical resection of the primary tumor without metastasectomy. Surgical resection was associated with a significant survival benefit on unadjusted analysis (median survival, 9.2 vs. 7.6 months; p < 0.01). After propensity matching to adjust for nonrandom treatment selection, surgical resection continued to be associated with a significant survival benefit (median survival, 9.2 vs. 7.3 months; p < 0.01).This study was limited by the potential for selection bias regarding which patients received surgical resection. There was also a lack of data regarding the indication for operation, specifically whether a patient was symptomatic or asymptomatic before resection. The inability to account for tumor size or grade among patients who did not receive surgical resection was another limitation.Surgical resection of the primary tumor without metastasectomy in patients with metastatic colorectal cancer is associated with improved survival as compared with chemotherapy/radiation therapy alone. Additional research is necessary to determine which patients may benefit from this intervention.

Authors
Gulack, BC; Nussbaum, DP; Keenan, JE; Ganapathi, AM; Sun, Z; Worni, M; Migaly, J; Mantyh, CR
MLA Citation
Gulack, BC, Nussbaum, DP, Keenan, JE, Ganapathi, AM, Sun, Z, Worni, M, Migaly, J, and Mantyh, CR. "Surgical Resection of the Primary Tumor in Stage IV Colorectal Cancer Without Metastasectomy is Associated With Improved Overall Survival Compared With Chemotherapy/Radiation Therapy Alone." Diseases of the colon and rectum 59.4 (April 2016): 299-305.
PMID
26953988
Source
epmc
Published In
Diseases of the Colon and Rectum
Volume
59
Issue
4
Publish Date
2016
Start Page
299
End Page
305
DOI
10.1097/dcr.0000000000000546

Intensity-Modulated Radiation Therapy Is Not Associated With Either Short-Term or Long-Term Benefit Over 3D-Conformal Radiotherapy for Rectal Cancer

Authors
Sun, Z; Adam, MA; Shenoi, M; Czito, B; Migaly, J; Mantyh, CR
MLA Citation
Sun, Z, Adam, MA, Shenoi, M, Czito, B, Migaly, J, and Mantyh, CR. "Intensity-Modulated Radiation Therapy Is Not Associated With Either Short-Term or Long-Term Benefit Over 3D-Conformal Radiotherapy for Rectal Cancer." April 2016.
Source
wos-lite
Published In
Gastroenterology
Volume
150
Issue
4
Publish Date
2016
Start Page
S1175
End Page
S1176

Thirty-Day Mortality Underestimates Incidence of Death After Colorectal Surgery for Cancer

Authors
Adam, MA; Sun, Z; Kim, J; Migaly, J; Mantyh, CR
MLA Citation
Adam, MA, Sun, Z, Kim, J, Migaly, J, and Mantyh, CR. "Thirty-Day Mortality Underestimates Incidence of Death After Colorectal Surgery for Cancer." April 2016.
Source
wos-lite
Published In
Gastroenterology
Volume
150
Issue
4
Publish Date
2016
Start Page
S1199
End Page
S1199

Determining the Optimal Timing for Initiation of Adjuvant Chemotherapy After Resection for Stage II and III Colon Cancer.

Several reports suggest that the efficacy of adjuvant chemotherapy on survival diminishes over time for colon cancer; however, precise timing of its loss of benefit has not been established.This study aimed to determine the relationship between time to adjuvant chemotherapy and survival and to identify a threshold for increased risk of mortality.This was a retrospective study. Multivariable Cox proportional hazard modeling with restricted cubic splines was used to evaluate the adjusted association between time to adjuvant chemotherapy and overall survival and to establish an optimal threshold for the initiation of therapy.Data were collected from the National Cancer Data Base.Adults who received adjuvant chemotherapy following resection of stage II to III colon cancers were selected.The primary outcome measured was overall survival.A total of 7794 patients were included. After adjusting for clinical, tumor, and treatment characteristics, our model determined a critical threshold of chemotherapy initiation at 44 days from surgery, after which there was an increase in the overall mortality. At a median follow-up of 61 months, the risk of mortality was increased in those who received adjuvant chemotherapy after 44 days from surgery (adjusted HR, 1.14; 95% CI, 1.05-1.24; p = 0.002), but not in those who received chemotherapy before 44 days from surgery (p = 0.11). Each additional week of delay was associated with a 7% decrease in survival (HR, 1.07; 95% CI, 1.04-1.10; p < 0.001).This study was limited by selection bias and the inability to compare specific chemotherapy regimens.This study objectively determines the optimal timing of adjuvant chemotherapy for patients with resected colon cancer. Delay beyond 6 weeks is associated with compromised survival. These findings emphasize the importance of the timely initiation of therapy, and suggest that efforts to enhance recovery following surgery have the potential to improve survival by decreasing delay to adjuvant chemotherapy.

Authors
Sun, Z; Adam, MA; Kim, J; Nussbaum, DP; Benrashid, E; Mantyh, CR; Migaly, J
MLA Citation
Sun, Z, Adam, MA, Kim, J, Nussbaum, DP, Benrashid, E, Mantyh, CR, and Migaly, J. "Determining the Optimal Timing for Initiation of Adjuvant Chemotherapy After Resection for Stage II and III Colon Cancer." Diseases of the colon and rectum 59.2 (February 2016): 87-93.
PMID
26734965
Source
epmc
Published In
Diseases of the Colon and Rectum
Volume
59
Issue
2
Publish Date
2016
Start Page
87
End Page
93
DOI
10.1097/dcr.0000000000000518

Mechanical bowel preps improve surgical outcomes in colorectal surgery.

Authors
Mantyh, C
MLA Citation
Mantyh, C. "Mechanical bowel preps improve surgical outcomes in colorectal surgery." Evidence-based medicine 21.1 (February 2016): 27-.
PMID
26660662
Source
epmc
Published In
Evidence-based medicine
Volume
21
Issue
1
Publish Date
2016
Start Page
27
DOI
10.1136/ebmed-2015-110323

Colonic arteriovenous malformations

© Springer International Publishing AG 2010, 2016. Arteriovenous malformations are degenerative vascular lesions of the gastrointestinal tract that result in lower gastrointestinal bleeding, especially in the elderly. Although self-limiting in most cases, symptomatic arteriovenous malformations can present with massive bleeding in 15 % of cases. This review discusses the clinical presentation, diagnostic workup, and management of colonic arteriovenous malformations.

Authors
Sun, Z; Adam, MA; Mantyh, CR
MLA Citation
Sun, Z, Adam, MA, and Mantyh, CR. "Colonic arteriovenous malformations." Gastrointestinal Bleeding: A Practical Approach to Diagnosis and Management, Second Edition. January 1, 2016. 159-167.
Source
scopus
Publish Date
2016
Start Page
159
End Page
167
DOI
10.1007/978-3-319-40646-6_14

Robotic Low Anterior Resection for Rectal Cancer: A National Perspective on Short-term Oncologic Outcomes.

This study examines short-term outcomes and pathologic surrogates of oncologic results among patients undergoing robotic versus laparoscopic low anterior resection for rectal cancer. A total of 6403 patients met inclusion criteria. Although the robotic approach required significantly fewer conversions to open, surrogates for proper oncologic surgery were nearly identical between the 2 approaches.Although laparoscopic low anterior resection (LLAR) has gained popularity as an acceptable approach, the robotic low anterior resection (RLAR) remains largely unproven. We compared short-term oncologic outcomes between rectal cancer patients undergoing either RLAR or LLAR.All patients with rectal cancer in the National Cancer Data Base undergoing RLAR or LLAR from 2010 to 2011 were included. Predictors of RLAR were modeled with multivariable logistic regression. Groups were matched on propensity to undergo RLAR. Primary endpoints included lymph node retrieval and margin status, whereas secondary 30-day outcomes were mortality, hospital length of stay (LOS), and unplanned readmission rates.A total of 6403 patients met inclusion criteria, of which 956 (14.9%) underwent RLAR. RLAR patients were more likely to be treated at academic centers, receive neoadjuvant therapy, and have higher T-stage and longer time to surgery (all P < 0.001). Neoadjuvant therapy and treatment at an academic/research center remained the only significant predictors of robotic use after multivariable adjustment. After propensity matching, RLAR was associated with lower conversion (9.5 vs 16.4%, P < 0.001). There were no significant differences in lymph node retrieval, margin status, 30-day mortality, readmission, or hospital LOS.In this largest series to date, we demonstrated equivalent perioperative safety and patient outcomes for robotic compared to LLAR in the setting of rectal cancer. Although the robotic approach required significantly fewer conversions to open, surrogates for proper oncologic surgery were nearly identical between the 2 approaches, suggesting that a robotic approach may be a suitable alternative. Further studies comparing long-term cancer recurrence and survival should be performed.

Authors
Speicher, PJ; Englum, BR; Ganapathi, AM; Nussbaum, DP; Mantyh, CR; Migaly, J
MLA Citation
Speicher, PJ, Englum, BR, Ganapathi, AM, Nussbaum, DP, Mantyh, CR, and Migaly, J. "Robotic Low Anterior Resection for Rectal Cancer: A National Perspective on Short-term Oncologic Outcomes." Annals of surgery 262.6 (December 2015): 1040-1045.
PMID
25405559
Source
epmc
Published In
Annals of Surgery
Volume
262
Issue
6
Publish Date
2015
Start Page
1040
End Page
1045
DOI
10.1097/sla.0000000000001017

Combined Mechanical and Oral Antibiotic Bowel Preparation Reduces Incisional Surgical Site Infection and Anastomotic Leak Rates After Elective Colorectal Resection: An Analysis of Colectomy-Targeted ACS NSQIP.

OBJECTIVE: To determine the association between preoperative bowel preparation and 30-day outcomes after elective colorectal resection. METHODS: Patients from the 2012 Colectomy-Targeted American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database who underwent elective colorectal resection were included for analysis and assigned to 1 of 4 groups based on the type of preoperative preparation they received [combined mechanical and oral antibiotic preparation (OAP), mechanical preparation only, OAP only, or no preoperative bowel preparation]. The association between preoperative bowel preparation status and 30-day postoperative outcomes was assessed using multivariate regression analysis to adjust for a robust array of patient- and procedure-related factors. RESULTS: A total of 4999 patients were included for this study [1494 received (29.9%) combined mechanical and OAP, 2322 (46.5%) received mechanical preparation only, 91 (1.8%) received OAP only, and 1092 (21.8%) received no preoperative preparation]. Compared to patients receiving no preoperative preparation, patients who received combined preparation demonstrated a lower 30-day incidence of postoperative incisional surgical site infection (3.2% vs 9.0%, P < 0.001), anastomotic leakage (2.8% vs 5.7%, P = 0.001), and procedure-related hospital readmission (5.5% vs 8.0%, P = 0.03). The outcomes of patients who received either mechanical or OAP alone did not differ significantly from those who received no preparation. CONCLUSIONS: Combined bowel preparation with mechanical cleansing and oral antibiotics results in a significantly lower incidence of incisional surgical site infection, anastomotic leakage, and hospital readmission when compared to no preoperative bowel preparation.

Authors
Scarborough, JE; Mantyh, CR; Sun, Z; Migaly, J
MLA Citation
Scarborough, JE, Mantyh, CR, Sun, Z, and Migaly, J. "Combined Mechanical and Oral Antibiotic Bowel Preparation Reduces Incisional Surgical Site Infection and Anastomotic Leak Rates After Elective Colorectal Resection: An Analysis of Colectomy-Targeted ACS NSQIP." Annals of surgery 262.2 (August 2015): 331-337.
PMID
26083870
Source
epmc
Published In
Annals of Surgery
Volume
262
Issue
2
Publish Date
2015
Start Page
331
End Page
337
DOI
10.1097/sla.0000000000001041

Improving Outcomes in Colorectal Surgery by Sequential Implementation of Multiple Standardized Care Programs.

BACKGROUND: The purpose of this study was to examine the impact of the sequential implementation of the enhanced recovery program (ERP) and surgical site infection bundle (SSIB) on short-term outcomes in colorectal surgery (CRS) to determine if the presence of multiple standardized care programs provides additive benefit. STUDY DESIGN: Institutional ACS-NSQIP data were used to identify patients who underwent elective CRS from September 2006 to March 2013. The cohort was stratified into 3 groups relative to implementation of the ERP (February 1, 2010) and SSIB (July 1, 2011). Unadjusted characteristics and 30-day outcomes were assessed, and inverse proportional weighting was then used to determine the adjusted effect of these programs. RESULTS: There were 787 patients included: 337, 165, and 285 in the pre-ERP/SSIB, post-ERP/pre-SSIB, and post-ERP/SSIB periods, respectively. After inverse probability weighting (IPW) adjustment, groups were balanced with respect to patient and procedural characteristics considered. Compared with the pre-ERP/SSIB group, the post-ERP/pre-SSIB group had significantly reduced length of hospitalization (8.3 vs 6.6 days, p = 0.01) but did not differ with respect to postoperative wound complications and sepsis. Subsequent introduction of the SSIB then resulted in a significant decrease in superficial SSI (16.1% vs 6.3%, p < 0.01) and postoperative sepsis (11.2% vs 1.8%, p < 0.01). Finally, inflation-adjusted mean hospital cost for a CRS admission fell from $31,926 in 2008 to $22,044 in 2013 (p < 0.01). CONCLUSIONS: Sequential implementation of the ERP and SSIB provided incremental improvements in CRS outcomes while controlling hospital costs, supporting their combined use as an effective strategy toward improving the quality of patient care.

Authors
Keenan, JE; Speicher, PJ; Nussbaum, DP; Adam, MA; Miller, TE; Mantyh, CR; Thacker, JKM
MLA Citation
Keenan, JE, Speicher, PJ, Nussbaum, DP, Adam, MA, Miller, TE, Mantyh, CR, and Thacker, JKM. "Improving Outcomes in Colorectal Surgery by Sequential Implementation of Multiple Standardized Care Programs." Journal of the American College of Surgeons 221.2 (August 2015): 404-14.e1.
Website
http://hdl.handle.net/10161/13949
PMID
26206639
Source
epmc
Published In
Journal of The American College of Surgeons
Volume
221
Issue
2
Publish Date
2015
Start Page
404
End Page
14.e1
DOI
10.1016/j.jamcollsurg.2015.04.008

Metastatic gallbladder cancer masquerading as primary colon malignancy.

Authors
Sun, Z; Galeotti, J; McCall, SJ; Mantyh, C
MLA Citation
Sun, Z, Galeotti, J, McCall, SJ, and Mantyh, C. "Metastatic gallbladder cancer masquerading as primary colon malignancy." Clinical Medicine Review Case Reports 2 (June 1, 2015): 1-3.
Source
manual
Published In
Clinical Medicine Review Case Reports
Volume
2
Publish Date
2015
Start Page
1
End Page
3

Laparoscopic versus open low anterior resection for rectal cancer: results from the national cancer data base.

While the use of laparoscopy has increased among patients undergoing colorectal surgery, there is ongoing debate regarding the oncologic equivalence of laparoscopy compared to open low anterior resection (LAR) for rectal cancer.The 2010-2011 NCDB was queried for patients undergoing LAR for rectal cancer. Subjects were grouped by laparoscopic (LLAR) versus open (OLAR) technique. Baseline characteristics were compared. Subjects were propensity matched, and outcomes were compared between groups.A total of 18,765 patients were identified (34.3% LLAR, 65.7% OLAR). After propensity matching, all baseline variables were highly similar except for carcinoembryonic antigen (CEA) level. Complete resection was more common in patients undergoing LLAR (91.6 vs. 88.9%, p < 0.001), and statistically significant benefits were observed for gross, microscopic, and circumferential (>1 mm) margins (all p < 0.001). There was no difference in median number of lymph nodes obtained (15 vs. 15). Patients undergoing LLAR had shorter lengths of stay (5 vs. 6 days, p < 0.001) without a corresponding increase in 30-day readmission rates (6 vs. 7%, p = 0.02).Laparoscopic LAR appears to result in equivalent short-term oncologic outcomes compared to the traditional open approach as measured via surrogate endpoints in the NCDB. While these results support the increasing use of laparoscopy in rectal surgery, further data are necessary to assess long-term outcomes.

Authors
Nussbaum, DP; Speicher, PJ; Ganapathi, AM; Englum, BR; Keenan, JE; Mantyh, CR; Migaly, J
MLA Citation
Nussbaum, DP, Speicher, PJ, Ganapathi, AM, Englum, BR, Keenan, JE, Mantyh, CR, and Migaly, J. "Laparoscopic versus open low anterior resection for rectal cancer: results from the national cancer data base." Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract 19.1 (January 2015): 124-131.
PMID
25091847
Source
epmc
Published In
Journal of Gastrointestinal Surgery
Volume
19
Issue
1
Publish Date
2015
Start Page
124
End Page
131
DOI
10.1007/s11605-014-2614-1

Wound classification reporting in HPB surgery: can a single word change public perception of institutional performance?

The drive to improve outcomes and the inevitability of mandated public reporting necessitate uniform documentation and accurate databases. The reporting of wound classification in patients undergoing hepato-pancreatico-biliary (HPB) surgery and the impact of inconsistencies on quality metrics were investigated.The 2005-2011 National Surgical Quality Improvement Program (NSQIP) participant use file was interrogated to identify patients undergoing HPB resections. The effect of wound classification on post-operative surgical site infection (SSI) rates was determined through logistic regression. The impact of variations in wound classification reporting on perceived outcomes was modelled by simulating observed-to-expected (O/E) ratios for SSI.In total, 27,376 patients were identified with significant heterogeneity in wound classification. In spite of clear guidelines prompting at least 'clean-contaminated' designation for HPB resections, 8% of all cases were coded as 'clean'. Contaminated [adjusted odds ratio (AOR): 1.39, P = 0.001] and dirty (AOR: 1.42, P = 0.02] cases were associated with higher odds of SSI, whereas clean-contaminated were not (P = 0.99). O/E ratios were highly sensitive to modest changes in wound classification.Perceived performance is affected by heterogeneous reporting of wound classification. As institutions work to improve outcomes and prepare for public reporting, it is imperative that all adhere to consistent reporting practices to provide accurate and reproducible outcomes.

Authors
Speicher, PJ; Nussbaum, DP; Scarborough, JE; Zani, S; White, RR; Blazer, DG; Mantyh, CR; Tyler, DS; Clary, BM
MLA Citation
Speicher, PJ, Nussbaum, DP, Scarborough, JE, Zani, S, White, RR, Blazer, DG, Mantyh, CR, Tyler, DS, and Clary, BM. "Wound classification reporting in HPB surgery: can a single word change public perception of institutional performance?." HPB : the official journal of the International Hepato Pancreato Biliary Association 16.12 (December 2014): 1068-1073.
PMID
24852206
Source
epmc
Published In
HPB
Volume
16
Issue
12
Publish Date
2014
Start Page
1068
End Page
1073
DOI
10.1111/hpb.12275

Adjuvant chemotherapy for t1 node-positive colon cancers provides significant survival benefit.

Contemporary treatment of node-positive (N+) colon cancer consists of adjuvant chemotherapy; however, randomized data supporting this practice were derived from lesions T2 or greater. Minimal data exist regarding the use and need for adjuvant chemotherapy in T1N+ disease.The aim of this study was to determine treatment trends and the effects of adjuvant chemotherapy on T1N+ colon cancers by using the National Cancer Database.This was a retrospective study. Baseline demographics, tumor, and cancer treatment characteristics were compared. Groups were matched on the propensity to receive chemotherapy. Adjusted long-term survival stratified by chemotherapy use was compared by using the Kaplan-Meier method with the log-rank test. Predictors of not receiving chemotherapy were identified by using a multivariable logistic regression model.Data were collected from the National Cancer Database, which collects cancer data from over 1500 cancer centers.We identified patients from 1998 to 2006 with T1N+ disease, excluding those with metastatic disease or previous cancer. Patients were stratified based on whether or not they received chemotherapy.The primary outcome measure of this study was long-term survival.Three thousand one hundred thirty-seven patients had T1N+ disease; 70.6% (n = 2216) received chemotherapy, and utilization significantly increased from 1998 to 2011 (p < 0.001). Unadjusted analysis revealed that patients treated with chemotherapy were statistically younger and healthier, and had shorter postoperative lengths of stay (all p < 0.001). Unadjusted 5-year survival was higher in patients receiving chemotherapy (87.9% vs 63.0% in patients with no chemotherapy; p < 0.001) and this persisted after propensity matching with (83.4% and 63.0% in patients with or without chemotherapy; p < 0.001). Only age (OR, 0.29; p < 0.001) predicted not receiving chemotherapy.Limitations include potential selection bias as well as the inability to compare disease-free survival/recurrence.Adjuvant chemotherapy appears to significantly improve long-term survival in patients receiving chemotherapy in T1N+ disease. Thus, the use of chemotherapy in T1N+ disease is justified and provides a highly significant survival benefit.

Authors
Ganapathi, AM; Speicher, PJ; Englum, BR; Castleberry, AW; Migaly, J; Hsu, DS; Mantyh, CR
MLA Citation
Ganapathi, AM, Speicher, PJ, Englum, BR, Castleberry, AW, Migaly, J, Hsu, DS, and Mantyh, CR. "Adjuvant chemotherapy for t1 node-positive colon cancers provides significant survival benefit." Diseases of the colon and rectum 57.12 (December 2014): 1341-1348.
PMID
25379998
Source
epmc
Published In
Diseases of the Colon and Rectum
Volume
57
Issue
12
Publish Date
2014
Start Page
1341
End Page
1348
DOI
10.1097/dcr.0000000000000245

The preventive surgical site infection bundle in colorectal surgery: an effective approach to surgical site infection reduction and health care cost savings.

IMPORTANCE: Surgical site infections (SSIs) in colorectal surgery are associated with increased morbidity and health care costs. OBJECTIVE: To determine the effect of a preventive SSI bundle (hereafter bundle) on SSI rates and costs in colorectal surgery. DESIGN: Retrospective study of institutional clinical and cost data. The study period was January 1, 2008, to December 31, 2012, and outcomes were assessed and compared before and after implementation of the bundle on July 1, 2011. SETTING AND PARTICIPANTS: Academic tertiary referral center among 559 patients who underwent major elective colorectal surgery. MAIN OUTCOMES AND MEASURES: The primary outcome was the rate of superficial SSIs before and after implementation of the bundle. Secondary outcomes included deep SSIs, organ-space SSIs, wound disruption, postoperative sepsis, length of stay, 30-day readmission, and variable direct costs of the index admission. RESULTS: Of 559 patients in the study, 346 (61.9%) and 213 (38.1%) underwent their operation before and after implementation of the bundle, respectively. Groups were matched on their propensity to be treated with the bundle to account for significant differences in the preimplementation and postimplementation characteristics. Comparison of the matched groups revealed that implementation of the bundle was associated with reduced superficial SSIs (19.3% vs 5.7%, P < .001) and postoperative sepsis (8.5% vs 2.4%, P = .009). No significant difference was observed in deep SSIs, organ-space SSIs, wound disruption, length of stay, 30-day readmission, or variable direct costs between the matched groups. However, in a subgroup analysis of the postbundle period, superficial SSI occurrence was associated with a 35.5% increase in variable direct costs ($13,253 vs $9779, P = .001) and a 71.7% increase in length of stay (7.9 vs 4.6 days, P < .001). CONCLUSIONS AND RELEVANCE: The preventive SSI bundle was associated with a substantial reduction in SSIs after colorectal surgery. The increased costs associated with SSIs support that the bundle represents an effective approach to reduce health care costs.

Authors
Keenan, JE; Speicher, PJ; Thacker, JKM; Walter, M; Kuchibhatla, M; Mantyh, CR
MLA Citation
Keenan, JE, Speicher, PJ, Thacker, JKM, Walter, M, Kuchibhatla, M, and Mantyh, CR. "The preventive surgical site infection bundle in colorectal surgery: an effective approach to surgical site infection reduction and health care cost savings." JAMA surgery 149.10 (October 2014): 1045-1052.
PMID
25163027
Source
epmc
Published In
JAMA Surgery
Volume
149
Issue
10
Publish Date
2014
Start Page
1045
End Page
1052
DOI
10.1001/jamasurg.2014.346

Modifizierter doppelt gestielter VRAM-Lappen zur simultanen Rekonstruktion eines Perineum- und posterioren vaginalen Defekts

Authors
Kokosis, G; Schmitz, R; Secord, AA; Havrilesky, LJ; Berchuck, A; Mantyh, CR; Erdmann, D
MLA Citation
Kokosis, G, Schmitz, R, Secord, AA, Havrilesky, LJ, Berchuck, A, Mantyh, CR, and Erdmann, D. "Modifizierter doppelt gestielter VRAM-Lappen zur simultanen Rekonstruktion eines Perineum- und posterioren vaginalen Defekts." Der Gynäkologe 47.10 (October 2014): 784-787.
Source
crossref
Published In
Der Gynäkologe
Volume
47
Issue
10
Publish Date
2014
Start Page
784
End Page
787
DOI
10.1007/s00129-014-3448-3

Surgical management of complex rectourethral fistulas in irradiated and nonirradiated patients.

BACKGROUND: Rectourethral fistulas are an uncommon, yet devastating occurrence after treatment for prostate cancer or trauma, and their surgical management has historically been nonstandardized. Anecdotally, irradiated rectourethral fistulas portend a worse prognosis. OBJECTIVE: To review outcomes after surgical treatment of rectourethral fistulas in radiated and nonirradiated patients to construct a logical surgical algorithm. DESIGN AND SETTING: A retrospective review was undertaken of all patients presenting to Duke University with the diagnosis of rectourethral fistula from 1996 to 2012. PATIENTS: Thirty-seven patients presented with and were treated for rectourethral fistulas: 21 received radiation, and a rectourethral fistula from trauma or iatrogenic injury developed in 16. MAIN OUTCOME MEASURES: The groups were compared regarding their functional outcomes, including healing, time to healing, continence, and recurrence. RESULTS: There were no significant differences in patient characteristics between groups. Patients who had irradiated rectourethral fistulas had a significantly higher rate of passage of urine through the rectum and wound infections, a higher rate of crystalloid infusion and blood transfusion requirements, and a longer time to ostomy reversal than nonirradiated patients. Patients who had irradiated rectourethral fistulas underwent more complex operative repairs, including gracilis interposition flaps (38%) and pelvic exenterations (19%), whereas nonirradiated patients most commonly underwent a York-Mason repair (50%). There were no statistically significant differences in rectourethral fistula healing or in postoperative and functional outcomes. Only 55% of irradiated patients had their ostomy reversed versus 91% in the nonirradiated group. LIMITATIONS: This study was limited by the small sample size and the retrospective nature of the review. CONCLUSIONS: Repair of rectourethral fistulas caused by radiation has a significantly higher wound infection rate and median time to healing, and lower overall stomal reversal rate than nonradiation-induced rectourethral fistulas. Patients who had irradiated rectourethral fistulas required significantly more complex operations, likely contributing to the higher morbidity, mortality, and lower fistula closure rate. We propose an algorithm for approaching rectourethral fistulas based on etiology.

Authors
Hanna, JM; Turley, R; Castleberry, A; Hopkins, T; Peterson, AC; Mantyh, C; Migaly, J
MLA Citation
Hanna, JM, Turley, R, Castleberry, A, Hopkins, T, Peterson, AC, Mantyh, C, and Migaly, J. "Surgical management of complex rectourethral fistulas in irradiated and nonirradiated patients." Diseases of the colon and rectum 57.9 (September 2014): 1105-1112.
PMID
25101607
Source
epmc
Published In
Diseases of the Colon and Rectum
Volume
57
Issue
9
Publish Date
2014
Start Page
1105
End Page
1112
DOI
10.1097/dcr.0000000000000175

Ureteral stenting in laparoscopic colorectal surgery.

BACKGROUND: Few studies have examined the current status of ureteral stent use or the indications for stenting, particularly in laparoscopic colorectal surgery. This study examines current national trends and predictors of ureteral stenting in patients undergoing major colorectal operations and the subsequent effects on perioperative outcomes. METHODS: The 2005-2011 National Surgical Quality Improvement participant user files were used to identify patients undergoing laparoscopic segmental colectomy, low anterior resection, or proctectomy. Trends in stent use were assessed across procedure types. To estimate the predictors of stent utilization, a forward-stepwise logistic regression model was used. A 3:1 nearest neighbor propensity match with subsequent multivariable adjustment was then used to estimate the impact of stents. RESULTS: A total of 42,311 cases were identified, of which 1795 (4.2%) underwent ureteral stent placement. Predictors of stent utilization included diverticular disease, need for radical resection (versus segmental colectomy), recent radiotherapy, and more recent calendar year. After adjustment, ureteral stenting appeared to be associated with a small increase in median operative time (44 min) and a trivial increase in length of stay (5.4%, P<0.001). However, there were no significant differences in morbidity or mortality. CONCLUSIONS: We describe the clinical predictors of ureteral stent usage in this patient population and report that while stenting adds to operative time, it is not associated with significantly increased morbidity or mortality after adjusting for diagnosis and comorbidities. Focused institutional studies are necessary in the future to address the utility of ureteral stents in the identification and possible prevention of iatrogenic injury.

Authors
Speicher, PJ; Goldsmith, ZG; Nussbaum, DP; Turley, RS; Peterson, AC; Mantyh, CR
MLA Citation
Speicher, PJ, Goldsmith, ZG, Nussbaum, DP, Turley, RS, Peterson, AC, and Mantyh, CR. "Ureteral stenting in laparoscopic colorectal surgery." The Journal of surgical research 190.1 (July 2014): 98-103.
PMID
24656474
Source
epmc
Published In
Journal of Surgical Research
Volume
190
Issue
1
Publish Date
2014
Start Page
98
End Page
103
DOI
10.1016/j.jss.2014.02.025

Rectourethral fistulas in the cancer survivor.

PURPOSE OF REVIEW: Iatrogenic rectourethral fistulas (RUFs) are a rare but challenging complication that can follow the treatment of prostate cancer. We review the literature regarding the surgical management of RUFs and subsequent outcomes, focusing on a cause-specific approach. RECENT FINDINGS: Iatrogenic RUFs are reported to occur in approximately 1% of patients treated with external-beam radiation therapy, in 1-6% of patients after radical prostatectomy, and in 5-9% following brachytherapy or cryotherapy after prostate cancer. Most of these patients will require surgical treatment at some point. Though there have been multiple surgical procedures described with varying degrees of success, there is no consensus as to the procedure of choice, though authors now agree on the importance of the interposition of healthy tissue in radiation-induced fistulas. SUMMARY: The current literature regarding surgical approaches to the iatrogenic RUF in the prostate cancer patient highlights the importance of a cause-specific and often multidisciplinary approach, as well as the one that is most familiar to the individual surgeon, because there is often little difference in the approaches in terms of recurrence. However, given the high success rate and low complication rate, muscle transposition flap repairs remain an attractive surgical option for fistulas with unfavorable local conditions such as those present after radiation.

Authors
Hanna, JM; Peterson, AC; Mantyh, C
MLA Citation
Hanna, JM, Peterson, AC, and Mantyh, C. "Rectourethral fistulas in the cancer survivor." Current opinion in urology 24.4 (July 2014): 382-388. (Review)
PMID
24841377
Source
epmc
Published In
Current Opinion in Urology
Volume
24
Issue
4
Publish Date
2014
Start Page
382
End Page
388
DOI
10.1097/mou.0000000000000073

Discrete improvement in racial disparity in survival among patients with stage IV colorectal cancer: a 21-year population-based analysis.

Recently, multiple clinical trials have demonstrated improved outcomes in patients with metastatic colorectal cancer. This study investigated if the improved survival is race dependent.Overall and cancer-specific survival of 77,490 White and Black patients with metastatic colorectal cancer from the 1988-2008 Surveillance Epidemiology and End Results registry were compared using unadjusted and multivariable adjusted Cox proportional hazard regression as well as competing risk analyses.Median age was 69 years, 47.4 % were female and 86.0 % White. Median survival was 11 months overall, with an overall increase from 8 to 14 months between 1988 and 2008. Overall survival increased from 8 to 14 months for White, and from 6 to 13 months for Black patients. After multivariable adjustment, the following parameters were associated with better survival: White, female, younger, better educated and married patients, patients with higher income and living in urban areas, patients with rectosigmoid junction and rectal cancer, undergoing cancer-directed surgery, having well/moderately differentiated, and N0 tumors (p < 0.05 for all covariates). Discrepancies in overall survival based on race did not change significantly over time; however, there was a significant decrease of cancer-specific survival discrepancies over time between White and Black patients with a hazard ratio of 0.995 (95 % confidence interval 0.991-1.000) per year (p = 0.03).A clinically relevant overall survival increase was found from 1988 to 2008 in this population-based analysis for both White and Black patients with metastatic colorectal cancer. Although both White and Black patients benefitted from this improvement, a slight discrepancy between the two groups remained.

Authors
Castleberry, AW; Güller, U; Tarantino, I; Berry, MF; Brügger, L; Warschkow, R; Cerny, T; Mantyh, CR; Candinas, D; Worni, M
MLA Citation
Castleberry, AW, Güller, U, Tarantino, I, Berry, MF, Brügger, L, Warschkow, R, Cerny, T, Mantyh, CR, Candinas, D, and Worni, M. "Discrete improvement in racial disparity in survival among patients with stage IV colorectal cancer: a 21-year population-based analysis." Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract 18.6 (June 2014): 1194-1204.
PMID
24733258
Source
epmc
Published In
Journal of Gastrointestinal Surgery
Volume
18
Issue
6
Publish Date
2014
Start Page
1194
End Page
1204
DOI
10.1007/s11605-014-2515-3

Reduced length of hospital stay in colorectal surgery after implementation of an enhanced recovery protocol.

BACKGROUND: Enhanced recovery after surgery (ERAS) is a multimodal approach to perioperative care that combines a range of interventions to enable early mobilization and feeding after surgery. We investigated the feasibility, clinical effectiveness, and cost savings of an ERAS program at a major U. S. teaching hospital. METHODS: Data were collected from consecutive patients undergoing open or laparoscopic colorectal surgery during 2 time periods, before and after implementation of an ERAS protocol. Data collected included patient demographics, operative, and perioperative surgical and anesthesia data, need for analgesics, complications, inpatient medical costs, and 30-day readmission rates. RESULTS: There were 99 patients in the traditional care group, and 142 in the ERAS group. The median length of stay (LOS) was 5 days in the ERAS group compared with 7 days in the traditional group (P < 0.001). The reduction in LOS was significant for both open procedures (median 6 vs 7 days, P = 0.01), and laparoscopic procedures (4 vs 6 days, P < 0.0001). ERAS patients had fewer urinary tract infections (13% vs 24%, P = 0.03). Readmission rates were lower in ERAS patients (9.8% vs 20.2%, P = 0.02). DISCUSSION: Implementation of an enhanced recovery protocol for colorectal surgery at a tertiary medical center was associated with a significantly reduced LOS and incidence of urinary tract infection. This is consistent with that of other studies in the literature and suggests that enhanced recovery programs could be implemented successfully and should be considered in U.S. hospitals.

Authors
Miller, TE; Thacker, JK; White, WD; Mantyh, C; Migaly, J; Jin, J; Roche, AM; Eisenstein, EL; Edwards, R; Anstrom, KJ; Moon, RE; Gan, TJ; Enhanced Recovery Study Group,
MLA Citation
Miller, TE, Thacker, JK, White, WD, Mantyh, C, Migaly, J, Jin, J, Roche, AM, Eisenstein, EL, Edwards, R, Anstrom, KJ, Moon, RE, Gan, TJ, and Enhanced Recovery Study Group, . "Reduced length of hospital stay in colorectal surgery after implementation of an enhanced recovery protocol." Anesthesia and analgesia 118.5 (May 2014): 1052-1061.
Website
http://hdl.handle.net/10161/8598
PMID
24781574
Source
epmc
Published In
Anesthesia and Analgesia
Volume
118
Issue
5
Publish Date
2014
Start Page
1052
End Page
1061
DOI
10.1213/ane.0000000000000206

Optimizing the Utilization of Adjuvant Chemotherapy Following Surgical Resection of Colon Cancer: A Comparison of Laparoscopic Versus Open Approach

Authors
Englum, BR; Speicher, PJ; Ganapathi, AM; Castleberry, A; Thacker, JK; Mantyh, CR; Migaly, J
MLA Citation
Englum, BR, Speicher, PJ, Ganapathi, AM, Castleberry, A, Thacker, JK, Mantyh, CR, and Migaly, J. "Optimizing the Utilization of Adjuvant Chemotherapy Following Surgical Resection of Colon Cancer: A Comparison of Laparoscopic Versus Open Approach." May 2014.
Source
wos-lite
Published In
Gastroenterology
Volume
146
Issue
5
Publish Date
2014
Start Page
S549
End Page
S549

Short-Term Oncologic Outcomes Are Superior Following Laparoscopic Versus Open Low Anterior Resection for Rectal Cancer: Results From the National Cancer Database

Authors
Nussbaum, DP; Speicher, PJ; Ganapathi, AM; Englum, BR; Keenan, JE; Mantyh, CR; Migaly, J
MLA Citation
Nussbaum, DP, Speicher, PJ, Ganapathi, AM, Englum, BR, Keenan, JE, Mantyh, CR, and Migaly, J. "Short-Term Oncologic Outcomes Are Superior Following Laparoscopic Versus Open Low Anterior Resection for Rectal Cancer: Results From the National Cancer Database." May 2014.
Source
wos-lite
Published In
Gastroenterology
Volume
146
Issue
5
Publish Date
2014
Start Page
S1033
End Page
S1033

Robotic Low Anterior Resection for Rectal Cancer and Short-Term Oncologic Outcomes

Authors
Speicher, PJ; Englum, BR; Ganapathi, AM; Mantyh, CR; Migaly, J
MLA Citation
Speicher, PJ, Englum, BR, Ganapathi, AM, Mantyh, CR, and Migaly, J. "Robotic Low Anterior Resection for Rectal Cancer and Short-Term Oncologic Outcomes." May 2014.
Source
wos-lite
Published In
Gastroenterology
Volume
146
Issue
5
Publish Date
2014
Start Page
S1019
End Page
S1019

Effects of Neoadjuvant and Adjuvant Therapy for Rectal Cancer on Long Term Survival

Authors
Mallipeddi, MK; Speicher, PJ; Ganapathi, AM; Englum, BR; Migaly, J; Mantyh, CR
MLA Citation
Mallipeddi, MK, Speicher, PJ, Ganapathi, AM, Englum, BR, Migaly, J, and Mantyh, CR. "Effects of Neoadjuvant and Adjuvant Therapy for Rectal Cancer on Long Term Survival." May 2014.
Source
wos-lite
Published In
Gastroenterology
Volume
146
Issue
5
Publish Date
2014
Start Page
S342
End Page
S342

The Effect of Surgical Approach on the Use of Adjuvant Chemotherapy Following Low Anterior Resection for Rectal Cancer

Authors
Ganapathi, AM; Englum, BR; Speicher, PJ; Castleberry, A; Thacker, JK; Mantyh, CR; Migaly, J
MLA Citation
Ganapathi, AM, Englum, BR, Speicher, PJ, Castleberry, A, Thacker, JK, Mantyh, CR, and Migaly, J. "The Effect of Surgical Approach on the Use of Adjuvant Chemotherapy Following Low Anterior Resection for Rectal Cancer." May 2014.
Source
wos-lite
Published In
Gastroenterology
Volume
146
Issue
5
Publish Date
2014
Start Page
S1080
End Page
S1081

A simple scoring system for risk-stratifying rectal cancer patients prior to radical resection.

Various predictors of perioperative risk for patients with rectal cancer undergoing radical resection have been well described, but no simple scoring system for surgeons to estimate this risk currently exists. The objective of this study was to develop a system for more accurate preoperative evaluations of competing risks and more informed shared decision-making with patients diagnosed with rectal cancer.The National Surgical Quality Improvement Program-Participant Use Data File for 2005-2011 was used to retrospectively identify patients undergoing radical resection for rectal cancer. A forward-stepwise multivariable logistic regression model was used to create a dynamic scoring system to preoperatively estimate a patient's risk of major complications.A total of 6,847 patients met study inclusion criteria. Thirteen risk factors were identified, and using these predictive variables, a scoring system was derived to stratify major complication risk after radical resection.The risk of a major complication after radical resection for rectal cancer is dependent on multiple preoperative variables. This study provides surgeons with a simple but effective tool for estimating major complication risk in rectal cancer patients prior to radical resection. This risk-stratification score serves as a patient-centered resource for discussing perioperative risks and assisting with the shared decision-making of operative planning.

Authors
Speicher, PJ; Ligh, C; Scarborough, JE; Thacker, JK; Mantyh, CR; Turley, RS; Migaly, J
MLA Citation
Speicher, PJ, Ligh, C, Scarborough, JE, Thacker, JK, Mantyh, CR, Turley, RS, and Migaly, J. "A simple scoring system for risk-stratifying rectal cancer patients prior to radical resection." Techniques in coloproctology 18.5 (May 2014): 459-465.
PMID
24085640
Source
epmc
Published In
Techniques in Coloproctology
Volume
18
Issue
5
Publish Date
2014
Start Page
459
End Page
465
DOI
10.1007/s10151-013-1076-x

Pelvic exenteration for the treatment of locally advanced colorectal and bladder malignancies in the modern era.

BACKGROUND: Although pelvic exenteration (PE) remains an important treatment for advanced pelvic malignancies, it has historically been associated with high morbidity and mortality with unclear long-term benefits. The objectives of this study were (1) estimate complication and mortality rates, (2) determine predictors of complications, and (3) estimate overall survival after PE for patients with locally advanced colorectal and bladder tumors. METHODS: A total of 377 patients were retrospectively identified from the 2005-2010 NSQIP PUF and an additional 1,111 from the 2004-2010 Surveillance Epidemiology and End Results database with T4M0 colorectal or bladder cancers. A logistic regression model was fitted to estimate early morbidity and mortality. The Kaplan-Meier method was used to estimate survival after PE compared to nonoperative management. RESULTS: Fifty-seven percent of patients had a complication, but 30-day mortality was only 2%. Patients with preoperative dyspnea and higher ASA class had the highest risk of morbidity. PE for the treatment of T4M0 rectal and bladder cancer was associated with significantly improved long-term survival compared to nonoperative therapy. CONCLUSIONS: PE is associated with a high complication rate but low 30-day mortality. The results of this study provide strong evidence to support PE as a viable treatment option for locally advanced rectal and bladder malignancies in appropriately selected patients.

Authors
Speicher, PJ; Turley, RS; Sloane, JL; Mantyh, CR; Migaly, J
MLA Citation
Speicher, PJ, Turley, RS, Sloane, JL, Mantyh, CR, and Migaly, J. "Pelvic exenteration for the treatment of locally advanced colorectal and bladder malignancies in the modern era." J Gastrointest Surg 18.4 (April 2014): 782-788.
PMID
24203585
Source
pubmed
Published In
Journal of Gastrointestinal Surgery
Volume
18
Issue
4
Publish Date
2014
Start Page
782
End Page
788
DOI
10.1007/s11605-013-2400-5

The Impact of Laparoscopic Versus Open Approach on Reoperation Rate After Segmental Colectomy: A Propensity Analysis

Background: Reoperation rate has not been well studied as a primary outcome when comparing laparoscopic with open approaches for colorectal resection. The goal of this study was to determine the impact of a laparoscopic approach on rate of reoperation after elective segmental colectomy. Methods: The NSQIP PUF for 2005-2011 was used to retrospectively identify patients who underwent open or laparoscopic elective segmental colectomy. The primary outcome measure was 30-day reoperation rate. A multivariable logistic regression model was constructed to determine the independent effect of surgical approach on rates of unplanned reoperation. This was validated with inverse propensity score weighting. Results: A total of 39,063 patients met the study inclusion criteria. A total of 1,702 reoperations were identified. After open approach, 5.1 % required reoperation, compared to 3.8 % in the laparoscopic group. After adjusting for confounders, open resection had 1.17-fold higher odds than laparoscopy for risk of reoperation, but this was not statistically significant (p = 0.07). Discussion: Using a large clinical dataset, we found that for segmental colectomy, there was not a statistically significant difference in odds of return to the operating room for laparoscopic versus open surgical approach. Reoperation is a relatively rare but costly complication and remains a potential area for quality improvement. © 2013 The Society for Surgery of the Alimentary Tract.

Authors
Speicher, PJ; Englum, BR; Jiang, B; Pietrobon, R; Mantyh, CR; Migaly, J
MLA Citation
Speicher, PJ, Englum, BR, Jiang, B, Pietrobon, R, Mantyh, CR, and Migaly, J. "The Impact of Laparoscopic Versus Open Approach on Reoperation Rate After Segmental Colectomy: A Propensity Analysis." February 1, 2014.
Source
scopus
Published In
Journal of Gastrointestinal Surgery
Volume
18
Issue
2
Publish Date
2014
Start Page
378
End Page
384
DOI
10.1007/s11605-013-2289-z

The impact of laparoscopic versus open approach on reoperation rate after segmental colectomy: a propensity analysis.

BACKGROUND: Reoperation rate has not been well studied as a primary outcome when comparing laparoscopic with open approaches for colorectal resection. The goal of this study was to determine the impact of a laparoscopic approach on rate of reoperation after elective segmental colectomy. METHODS: The NSQIP PUF for 2005-2011 was used to retrospectively identify patients who underwent open or laparoscopic elective segmental colectomy. The primary outcome measure was 30-day reoperation rate. A multivariable logistic regression model was constructed to determine the independent effect of surgical approach on rates of unplanned reoperation. This was validated with inverse propensity score weighting. RESULTS: A total of 39,063 patients met the study inclusion criteria. A total of 1,702 reoperations were identified. After open approach, 5.1 % required reoperation, compared to 3.8 % in the laparoscopic group. After adjusting for confounders, open resection had 1.17-fold higher odds than laparoscopy for risk of reoperation, but this was not statistically significant (p = 0.07). DISCUSSION: Using a large clinical dataset, we found that for segmental colectomy, there was not a statistically significant difference in odds of return to the operating room for laparoscopic versus open surgical approach. Reoperation is a relatively rare but costly complication and remains a potential area for quality improvement.

Authors
Speicher, PJ; Englum, BR; Jiang, B; Pietrobon, R; Mantyh, CR; Migaly, J
MLA Citation
Speicher, PJ, Englum, BR, Jiang, B, Pietrobon, R, Mantyh, CR, and Migaly, J. "The impact of laparoscopic versus open approach on reoperation rate after segmental colectomy: a propensity analysis." J Gastrointest Surg 18.2 (February 2014): 378-384.
PMID
23897083
Source
pubmed
Published In
Journal of Gastrointestinal Surgery
Volume
18
Issue
2
Publish Date
2014
Start Page
378
End Page
384
DOI
10.1007/s11605-013-2289-z

A modified bipedicle VRAM flap for simultaneous reconstruction of a perineal and posterior vaginal defect

© 2014, Springer-Verlag Berlin Heidelberg. The management of locally advanced pelvic tumors regularly requires radical surgical resection. The resection results in significant intrinsic and extrinsic pelvic defects. The advent of composite flaps has revolutionized vaginal and perineal reconstruction. Flaps provide bulky tissue to obliterate dead space, recruit vascularized tissue to an irradiated area and facilitate the skin closure. The authors present a modified vertical rectus abdominis myocutaneous (VRAM) flap for simultaneous reconstruction of a perineal and posterior vaginal defect following radical pelvic and abdominoperineal resection, based on two individual perforators off the inferior epigastric artery and vein with an excellent outcome. The English full-text version of this article is available at SpringerLink (under supplemental).

Authors
Kokosis, G; Schmitz, R; Secord, AA; Havrilesky, LJ; Berchuck, A; Mantyh, CR; Erdmann, D
MLA Citation
Kokosis, G, Schmitz, R, Secord, AA, Havrilesky, LJ, Berchuck, A, Mantyh, CR, and Erdmann, D. "A modified bipedicle VRAM flap for simultaneous reconstruction of a perineal and posterior vaginal defect." Gynakologe 47.10 (January 1, 2014): 784-787.
Source
scopus
Published In
Der Gynäkologe
Volume
47
Issue
10
Publish Date
2014
Start Page
784
End Page
787
DOI
10.1007/s00129-014-3448-3

Outcomes of Lung Transplant Patients With Severe GI Complications

Authors
Erhunmwunsee, L; Hanna, JM; Castleberry, A; Hartwig, M; Mantyh, CR
MLA Citation
Erhunmwunsee, L, Hanna, JM, Castleberry, A, Hartwig, M, and Mantyh, CR. "Outcomes of Lung Transplant Patients With Severe GI Complications." May 2013.
Source
wos-lite
Published In
Gastroenterology
Volume
144
Issue
5
Publish Date
2013
Start Page
S1089
End Page
S1089

A 10-year longitudinal analysis of surgical management for acute ischemic colitis.

Our objective was to review our 10-year experience of surgical resection for acute ischemic colitis (IC) and to assess the predictive value of previously reported risk-stratification methods.We retrospectively reviewed all adult patients at our institution undergoing colectomy for acute IC between 2000 and 2009. Descriptive statistics were calculated. Long-term survival was assessed using Kaplan-Meier methods and in-hospital mortality using multivariate logistic regression. Patients were risk-stratified based on previously reported methods, and discriminatory accuracy of predicting in-hospital mortality was evaluated by the area under the curve (AUC) of the receiver operating characteristic (ROC) curve.A total of 115 patients were included for analysis, of which 37 % (n = 43) died in-hospital. The median survival was 4.9 months for all patients and 43.6 months for patients surviving to discharge. Seventeen patients subsequently underwent end-ostomy reversal at our institution, with in-hospital mortality of 18 % (n = 3) and ICU admission for 35 % (n = 6). The discriminatory accuracy of risk stratification in predicting in-hospital mortality based on ROC AUC was 0.75.Acute IC continues to remain a very deadly disease. Patients who survive the initial acute IC insult can achieve long-term survival; however, we experienced high rates of death and complications following elective end-ostomy reversal. Risk stratification provides reasonable accuracy in predicting postoperative mortality.

Authors
Castleberry, AW; Turley, RS; Hanna, JM; Hopkins, TJ; Barbas, AS; Worni, M; Mantyh, CR; Migaly, J
MLA Citation
Castleberry, AW, Turley, RS, Hanna, JM, Hopkins, TJ, Barbas, AS, Worni, M, Mantyh, CR, and Migaly, J. "A 10-year longitudinal analysis of surgical management for acute ischemic colitis." Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract 17.4 (April 2013): 784-792.
PMID
23242848
Source
epmc
Published In
Journal of Gastrointestinal Surgery
Volume
17
Issue
4
Publish Date
2013
Start Page
784
End Page
792
DOI
10.1007/s11605-012-2117-x

Intraoperative pelvic brachytherapy for treatment of locally advanced or recurrent colorectal cancer.

The aim of this study was to evaluate the efficacy and morbidity of intraoperative radiation therapy (IORT) for advanced colorectal cancer.All patients undergoing IORT for locally advanced rectal cancer from 2001-2009 were reviewed for cancer recurrence, survival, and procedure-related morbidity. Cumulative event rates were estimated using the method of Kaplan and Meier.Twenty-nine patients with locally advanced (n = 8) or recurrent (n = 21) rectal cancers were treated with IORT and resection. Surgical interventions included low anterior resection, abdominoperineal resection, pelvic exenteration, and a variety of non-anatomic resections of pelvic recurrences. R(0) resections were achieved in 16 patients, while R(1) resections were achieved in 10, and margins were grossly positive in 3 patients. IORT was delivered to all patients over a median area of 48 (42-72) cm(2) at a median dose of 12 (12-15) Gy. Local and overall recurrence rates were 24 % (locally advanced group) and 45 % (recurrent group). Median disease-free and overall survival were 25 and 40 months respectively at a median follow-up of 26 (18-42) months. The short-term (≤30 days) complication rate was 45 %. Eight patients developed local wound complications, 5 of which required operative intervention. Four patients developed intra-abdominal abscesses requiring drainage. Long-term (>30 days) complications were identified in 11 patients (38 %) and included long-term wound complications (n = 3), ureteral obstruction requiring stenting (n = 1), neurogenic bladder (n = 3), enteric fistulae (n = 2), small bowel obstruction (n = 1), and neuropathic pain (n = 1).Intraoperative brachytherapy is a viable IORT option during pelvic surgery for locally advanced or recurrent colorectal cancer but is associated with high postoperative morbidity. Whether intraoperative brachytherapy can improve local recurrence rates for locally advanced or recurrent colorectal cancer will require further prospective investigation.

Authors
Turley, RS; Czito, BG; Haney, JC; Tyler, DS; Mantyh, CR; Migaly, J
MLA Citation
Turley, RS, Czito, BG, Haney, JC, Tyler, DS, Mantyh, CR, and Migaly, J. "Intraoperative pelvic brachytherapy for treatment of locally advanced or recurrent colorectal cancer." Techniques in coloproctology 17.1 (February 2013): 95-100.
PMID
22986843
Source
epmc
Published In
Techniques in Coloproctology
Volume
17
Issue
1
Publish Date
2013
Start Page
95
End Page
100
DOI
10.1007/s10151-012-0892-8

Minimally invasive surgery for diverticulitis.

The realm of minimally invasive surgery now encompasses the majority of abdominal operations in the field of colorectal surgery. Diverticulitis, a common pathology seen in most colorectal practices, poses unique challenges to surgeons implementing laparoscopic surgery in their practices due to the presence of an inflammatory phlegmon and distorted anatomical planes, which increase the difficulty of the operation. Although the majority of colon resections for diverticulitis are still performed through a standard laparotomy incision, laparoscopic techniques are becoming increasingly common. A large body of literature now supports laparoscopic surgery to be safe and effective as well as to provide significant advantages over open surgery for diverticular disease. Here, we review the most current literature supporting laparoscopic surgery for elective and emergent treatment of diverticulitis.

Authors
Turley, RS; Mantyh, CR; Migaly, J
MLA Citation
Turley, RS, Mantyh, CR, and Migaly, J. "Minimally invasive surgery for diverticulitis." Techniques in coloproctology 17 Suppl 1 (February 2013): S11-S22. (Review)
PMID
23250639
Source
epmc
Published In
Techniques in Coloproctology
Volume
17 Suppl 1
Publish Date
2013
Start Page
S11
End Page
S22
DOI
10.1007/s10151-012-0940-4

Laparoscopic versus open Hartmann procedure for the emergency treatment of diverticulitis: a propensity-matched analysis.

A laparoscopic approach has been proposed to reduce the high morbidity and mortality associated with the Hartmann procedure for the emergency treatment of diverticulitis.The objective of our study was to determine whether a laparoscopic Hartmann procedure reduces early morbidity or mortality for patients undergoing an emergency operation for diverticulitis.This is a comparative effectiveness study. A subset of the entire American College of Surgeons National Surgical Quality Improvement Program patient sample matched on propensity for undergoing their procedure with the laparoscopic approach were used to compare postoperative outcomes between laparoscopic and open groups.This study uses data from the American College of Surgeons National Surgical Quality Improvement Program Participant User Files from 2005 through 2009.All patients who underwent an emergency laparoscopic or open partial colectomy with end colostomy for colonic diverticulitis were reviewed.The main outcome measures were 30-day mortality and morbidity.Included in the analysis were 1186 patients undergoing emergency partial colectomy with end colostomy for diverticulitis. Among the entire cohort, the laparoscopic group had fewer overall complications (26% vs 41.7%, p = 0.008) and shorter mean length of hospitalization (8.9 vs 11.6 days, p = 0.0008). Operative times were not significantly different between groups. When controlling for potential confounders, a laparoscopic approach was not associated with a decrease in morbidity or mortality. In comparison with a propensity-match cohort, the laparoscopic approach did not reduce postoperative morbidity or mortality.This study is limited by its retrospective nature and the absence of pertinent variables such as postoperative pain indices, time for return of bowel function, and rates of readmission.A laparoscopic approach to the Hartmann procedure for the emergency treatment of complicated diverticulitis does not significantly decrease postoperative morbidity or mortality in comparison with the open technique.

Authors
Turley, RS; Barbas, AS; Lidsky, ME; Mantyh, CR; Migaly, J; Scarborough, JE
MLA Citation
Turley, RS, Barbas, AS, Lidsky, ME, Mantyh, CR, Migaly, J, and Scarborough, JE. "Laparoscopic versus open Hartmann procedure for the emergency treatment of diverticulitis: a propensity-matched analysis." Diseases of the colon and rectum 56.1 (January 2013): 72-82.
PMID
23222283
Source
epmc
Published In
Diseases of the Colon and Rectum
Volume
56
Issue
1
Publish Date
2013
Start Page
72
End Page
82
DOI
10.1097/dcr.0b013e3182749cf5

Minimally invasive surgery for diverticulitis

The realm of minimally invasive surgery now encompasses the majority of abdominal operations in the field of colorectal surgery. Diverticulitis, a common pathology seen in most colorectal practices, poses unique challenges to surgeons implementing laparoscopic surgery in their practices due to the presence of an inflammatory phlegmon and distorted anatomical planes, which increase the difficulty of the operation. Although the majority of colon resections for diverticulitis are still performed through a standard laparotomy incision, laparoscopic techniques are becoming increasingly common. A large body of literature now supports laparoscopic surgery to be safe and effective as well as to provide significant advantages over open surgery for diverticular disease. Here, we review the most current literature supporting laparoscopic surgery for elective and emergent treatment of diverticulitis. © Springer-Verlag Italia 2012.

Authors
Turley, RS; Mantyh, CR; Migaly, J
MLA Citation
Turley, RS, Mantyh, CR, and Migaly, J. "Minimally invasive surgery for diverticulitis." Techniques in Coloproctology 17.SUPPL.1 (2013): S11-S22.
Source
scival
Published In
Techniques in Coloproctology
Volume
17
Issue
SUPPL.1
Publish Date
2013
Start Page
S11
End Page
S22
DOI
10.1007/s10151-012-0940-4

Is there a role for simultaneous hepatic and colorectal resections? A contemporary view from NSQIP.

INTRODUCTION: The optimal timing of primary and metastatic tumor management in patients with synchronous hepatic colorectal metastases remains controversial. We aimed to compare perioperative outcomes of simultaneous colorectal/liver resection (SCLR) with isolated resections utilizing a national clinical database. METHODS: NSQIP data from 2005 to 2009 were examined to construct risk-adjusted generalized linear models and to calculate group-specific predicted estimates. These were used to compare 30-day perioperative outcomes among patients undergoing SCLR with colorectal (CR) and liver resections (LR) only in patients with metastatic colorectal cancer. RESULTS: A total of 3,983 patients were identified, who underwent SCLR (192), LR (1,857), or CR (1,934). Rectal resection was performed in 45 (23.4 %) SCLR patients and 269 (13.9 %) CR patients (p < 0.001). Major hepatectomy was performed in 69 (35.9 %) SCLR patients and 774 (41.7 %) LR patients (p = 0.12). Median adjusted operation time (SCLR: 273 min, 95 % CI: 253-295; CR: 172, CI: 168-177; LR: 222, CI: 217-228; p < 0.001) and median adjusted length of hospital stay (SCLR: 9.5 days, CI: 8.8-10.4; CR: 8.1, CI: 7.9-8.3; LR: 6.4, CI: 6.3-6.6; p < 0.001) were longer for SCLR compared to CR and LR. Adjusted predicted risks for at least one postoperative complication were higher in SCLR (36.3 %) than in CR (26.6 %) and LR (19.8 %) (p < 0.003), mostly due to infectious/cardiopulmonary issues. DISCUSSION: In SCLR patients, the risk of 30-day adverse outcomes is higher, and median operation time as well as length of hospital stay is longer compared to CR and LR patients. However, the expected combined morbidities of staged procedures though likely favor SCLR in carefully selected patients undergoing even complex hepatic and colorectal resections and should be considered.

Authors
Worni, M; Mantyh, CR; Akushevich, I; Pietrobon, R; Clary, BM
MLA Citation
Worni, M, Mantyh, CR, Akushevich, I, Pietrobon, R, and Clary, BM. "Is there a role for simultaneous hepatic and colorectal resections? A contemporary view from NSQIP." J Gastrointest Surg 16.11 (November 2012): 2074-2085.
Website
http://hdl.handle.net/10161/14849
PMID
22972010
Source
pubmed
Published In
Journal of Gastrointestinal Surgery
Volume
16
Issue
11
Publish Date
2012
Start Page
2074
End Page
2085
DOI
10.1007/s11605-012-1990-7

Effect of surgeon specialization on long-term survival following colon cancer resection at an NCI-designated cancer center.

BACKGROUND: Recent studies have documented improved outcomes for patients undergoing colorectal cancer resection at NCI cancer centers compared to hospitals without this designation. Proposed contributory factors include a higher proportion of surgeons with specialty training in colorectal surgery and surgical oncology. The purpose of this study was to assess whether surgeon specialization is associated with differences in overall survival following colon cancer resection at an NCI cancer center. METHODS: We conducted a retrospective review of patients undergoing colectomy for colon cancer from 1994 to 2009 at Duke University Medical Center. Patients were divided into two groups based on specialization status of the attending surgeon, and several clinicopathologic variables were compared. A multivariate analysis was then performed examining variables influencing overall survival. RESULTS: Total of 395 patients were included in the study, with 335 patients operated on by specialty-trained surgeons and 60 patients operated on by non-specialists. Overall, the two groups were similar with respect to demographic and pathologic variables. On multivariate analysis, surgeon specialization was found to be an independent predictor of improved overall survival [HR 0.43 (CI: 0.25-0.75), P = 0.003]. CONCLUSION: Surgeon specialization appears to be associated with improved overall survival in the setting of an NCI-designated cancer center.

Authors
Barbas, AS; Turley, RS; Mantyh, CR; Migaly, J
MLA Citation
Barbas, AS, Turley, RS, Mantyh, CR, and Migaly, J. "Effect of surgeon specialization on long-term survival following colon cancer resection at an NCI-designated cancer center." Journal of surgical oncology 106.3 (September 2012): 219-223.
PMID
22105839
Source
epmc
Published In
Journal of Surgical Oncology
Volume
106
Issue
3
Publish Date
2012
Start Page
219
End Page
223
DOI
10.1002/jso.22154

Ex vivo evaluation of preoperatively treated rectal cancer specimens of patients undergoing radical resection.

BACKGROUND: Previous reports have suggested that a subset of patients with advanced rectal cancer that demonstrate minimal or no residual disease after neoadjuvant treatment may either be followed closely or may undergo local resection. We prospectively evaluated ex vivo local excision specimens of patients undergoing radical resection after preoperative chemoradiation. METHODS: Patients with newly diagnosed rectal cancer received preoperative chemoradiotherapy followed by total mesorectal excision. Once removed, an ex vivo excision of the tumor bed mimicking a local excision was performed on the back table. Both the ex vivo and mesorectal specimens were inked and assessed. RESULTS: Thirty-seven rectal cancer patients (38% stage II, 62% stage III) were prospectively enrolled onto this study. Tumor downstaging occurred in 35% and nodal status downstaging in 16% of patients. The margins around the primary tumor on all ex vivo local excision specimens were negative. Twenty-nine percent of preoperatively staged stage II cancers either remained at stage II or were upstaged to stage III (21%), while 52% of stage III tumors remained node positive at final pathologic examination. The overall complete response rate was 14%. CONCLUSIONS: A significant number of stage II cancers will have positive nodes at final pathology, and most stage III rectal cancers will remain so at final pathologic examination. Given the high percentage of patients with positive lymph nodes after chemoradiation, radical resection is still recommended for cure for stage II and III rectal cancers.

Authors
de la Fuente, SG; Ludwig, KA; Tyler, DS; Mantyh, CR
MLA Citation
de la Fuente, SG, Ludwig, KA, Tyler, DS, and Mantyh, CR. "Ex vivo evaluation of preoperatively treated rectal cancer specimens of patients undergoing radical resection." Ann Surg Oncol 19.6 (June 2012): 1954-1958.
PMID
22350598
Source
pubmed
Published In
Annals of Surgical Oncology
Volume
19
Issue
6
Publish Date
2012
Start Page
1954
End Page
1958
DOI
10.1245/s10434-012-2259-9

Is There a Role for Simultaneous Hepatic and Colorectal Resections? a Contemporary View From NSQIP

Authors
Worni, M; Mantyh, CR; Akushevich, I; Pietrobon, R; Clary, BM
MLA Citation
Worni, M, Mantyh, CR, Akushevich, I, Pietrobon, R, and Clary, BM. "Is There a Role for Simultaneous Hepatic and Colorectal Resections? a Contemporary View From NSQIP." May 2012.
Source
wos-lite
Published In
Gastroenterology
Volume
142
Issue
5
Publish Date
2012
Start Page
S1042
End Page
S1042

Bevacizumab-associated fistula formation in postoperative colorectal cancer patients.

BACKGROUND: Adjuvant chemotherapy regimens for metastatic colorectal cancer (CRC) routinely include bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor (VEGF). We have identified a correlation between bevacizumab and fistula formation after resection of advanced CRC. STUDY DESIGN: Patients undergoing treatment with bevacizumab for metastatic CRC after 2005 were identified and reviewed. Of 222 consecutive patients, 9 patients treated with bevacizumab subsequently developed fistulas. These patients' charts were reviewed with attention to diagnosis, timing of operation relative to bevacizumab therapy, location of fistula, and fistula treatment. RESULTS: Of the 9 identified patients (9 of 222, 4.1%), 6 had rectal cancer, 2 had colon cancer, and 1 had synchronous CRC. Fistulas were most commonly anal or perineal (6 of 9, 66.7%) and colovesicular (3 of 9, 33%). On average, bevacizumab was initiated 23.6 months after the initial operation; complications occurred 3.9 months after starting bevacizumab. Nearly uniformly, cessation of bevacizumab led to fistula healing; however, 3 patients (33%) required fecal diversion. CONCLUSIONS: Bevacizumab is the most common antiangiogenesis agent used for treatment of metastatic CRC. Previous adverse events associated with bevacizumab treatment include venous thromboembolism, poor wound healing, and spontaneous bowel perforation. In this report, late postoperative development of fistulas occurred relatively soon after initiation of bevacizumab and usually spontaneously resolved with cessation of bevacizumab treatment. Based on the timing of fistula development relative to operation and initiation of bevacizumab, fistulas are likely secondary to bevacizumab therapy rather than postsurgical complications. Bevacizumab-induced fistulas occur in a small, but significant proportion of CRC patients and must be recognized early.

Authors
Ganapathi, AM; Westmoreland, T; Tyler, D; Mantyh, CR
MLA Citation
Ganapathi, AM, Westmoreland, T, Tyler, D, and Mantyh, CR. "Bevacizumab-associated fistula formation in postoperative colorectal cancer patients." Journal of the American College of Surgeons 214.4 (April 2012): 582-588.
PMID
22321523
Source
epmc
Published In
Journal of The American College of Surgeons
Volume
214
Issue
4
Publish Date
2012
Start Page
582
End Page
588
DOI
10.1016/j.jamcollsurg.2011.12.030

Laparoscopic vs. Open Resection for Rectal Cancer: A Comparison of Short-term Outcomes

Authors
De Rosa, N; Scarborough, J; Mantyh, CR
MLA Citation
De Rosa, N, Scarborough, J, and Mantyh, CR. "Laparoscopic vs. Open Resection for Rectal Cancer: A Comparison of Short-term Outcomes." February 2012.
Source
wos-lite
Published In
Annals of Surgical Oncology
Volume
19
Publish Date
2012
Start Page
S107
End Page
S108

Histological and molecular evaluation of patient-derived colorectal cancer explants.

Mouse models have been developed to investigate colorectal cancer etiology and evaluate new anti-cancer therapies. While genetically engineered and carcinogen-induced mouse models have provided important information with regard to the mechanisms underlying the oncogenic process, tumor xenograft models remain the standard for the evaluation of new chemotherapy and targeted drug treatments for clinical use. However, it remains unclear to what extent explanted colorectal tumor tissues retain inherent pathological features over time. In this study, we have generated a panel of 27 patient-derived colorectal cancer explants (PDCCEs) by direct transplantation of human colorectal cancer tissues into NOD-SCID mice. Using this panel, we performed a comparison of histology, gene expression and mutation status between PDCCEs and the original human tissues from which they were derived. Our findings demonstrate that PDCCEs maintain key histological features, basic gene expression patterns and KRAS/BRAF mutation status through multiple passages. Altogether, these findings suggest that PDCCEs maintain similarity to the patient tumor from which they are derived and may have the potential to serve as a reliable preclinical model that can be incorporated into future strategies to optimize individual therapy for patients with colorectal cancer.

Authors
Uronis, JM; Osada, T; McCall, S; Yang, XY; Mantyh, C; Morse, MA; Lyerly, HK; Clary, BM; Hsu, DS
MLA Citation
Uronis, JM, Osada, T, McCall, S, Yang, XY, Mantyh, C, Morse, MA, Lyerly, HK, Clary, BM, and Hsu, DS. "Histological and molecular evaluation of patient-derived colorectal cancer explants." PLoS One 7.6 (2012): e38422-.
PMID
22675560
Source
pubmed
Published In
PloS one
Volume
7
Issue
6
Publish Date
2012
Start Page
e38422
DOI
10.1371/journal.pone.0038422

Detection of intestinal dysplasia using angle-resolved low coherence interferometry.

Angle-resolved low coherence interferometry (a/LCI) is an optical biopsy technique that allows for depth-resolved, label-free measurement of the average size and optical density of cell nuclei in epithelial tissue to assess the tissue health. a/LCI has previously been used clinically to identify the presence of dysplasia in Barrett's Esophagus patients undergoing routine surveillance. We present the results of a pilot, ex vivo study of tissues from 27 patients undergoing partial colonic resection surgery, conducted to evaluate the ability of a/LCI to identify dysplasia. Performance was determined by comparing the nuclear morphology measurements with pathological assessment of co-located physical biopsies. A statistically significant correlation between increased average nuclear size, reduced nuclear density, and the presence of dysplasia was noted at the basal layer of the epithelium, at a depth of 200 to 300 μm beneath the tissue surface. Using a decision line determined from a receiver operating characteristic, a/LCI was able to separate dysplastic from healthy tissues with a sensitivity of 92.9% (13/14), a specificity of 83.6% (56/67), and an overall accuracy of 85.2% (69/81). The study illustrates the extension of the a/LCI technique to the detection of intestinal dysplasia, and demonstrates the need for future in vivo studies.

Authors
Terry, N; Zhu, Y; Thacker, JKM; Migaly, J; Guy, C; Mantyh, CR; Wax, A
MLA Citation
Terry, N, Zhu, Y, Thacker, JKM, Migaly, J, Guy, C, Mantyh, CR, and Wax, A. "Detection of intestinal dysplasia using angle-resolved low coherence interferometry." Journal of Biomedical Optics 16.10 (October 2011): 106002-.
PMID
22029349
Source
epmc
Published In
Journal of Biomedical Optics
Volume
16
Issue
10
Publish Date
2011
Start Page
106002
DOI
10.1117/1.3631799

Advanced fellowship training is associated with improved lymph node retrieval in colon cancer resections.

BACKGROUND: Examination of at least 12 lymph nodes has been established as the standard of care for adequate staging of colon cancer. The purpose of this study was to determine whether surgeon fellowship training, patient body mass index (BMI), and surgical approach (open versus laparoscopic) are important factors associated with lymph node retrieval at an NCI/NCCN-designated center. METHODS: We conducted a retrospective review of patients undergoing colectomy for colon cancer from 1994 to 2009. Patients who underwent right, left, and sigmoid colectomy by open or laparoscopic approaches were included. Lymph node retrieval and risk factors for inadequate nodal retrieval (<12 nodes) were analyzed. RESULTS: A total of 371 patients were included. Lymph node retrieval was found to be significantly increased when surgeons had fellowship training compared with no advanced training (19.9 ± 10.6 versus 14.8 ± 10.6, P = 0.0007). Lymph node retrieval was found to be significantly decreased in obese patients (BMI ≥ 30) compared with non-obese patients (17.3 ± 10.0 versus 19.9 ± 11.5, P = 0.05). There was no significant difference between open and laparoscopic approaches. On multivariate analysis, lack of fellowship training, surgery performed prior to establishment of NCI guidelines for lymph node retrieval, and small tumor size were independent predictors of inadequate lymph node retrieval. CONCLUSION: Advanced fellowship training of surgeons appears to be associated with higher lymph node retrieval and decreased risk of performing inadequate nodal retrieval. Small tumor size and surgery performed prior to establishment of the 12 lymph node benchmark were also associated with inadequate nodal retrieval.

Authors
Barbas, A; Turley, R; Mantyh, C; Migaly, J
MLA Citation
Barbas, A, Turley, R, Mantyh, C, and Migaly, J. "Advanced fellowship training is associated with improved lymph node retrieval in colon cancer resections." The Journal of surgical research 170.1 (September 2011): e41-e46.
PMID
21612795
Source
epmc
Published In
Journal of Surgical Research
Volume
170
Issue
1
Publish Date
2011
Start Page
e41
End Page
e46
DOI
10.1016/j.jss.2011.03.055

Complex abdominal wall hernias: a new classification system and approach to management based on review of 133 consecutive patients.

BACKGROUND: Plastic surgeons are increasingly involved in the repair of complex ventral hernias. Although this typically involves recurrent incisional hernias, operative strategies can be applied to most abdominal wall defects, including chronic wounds with or without exposed mesh, enterocutaneous fistulas, or hernias associated with significant pannus formation. METHODS: This is a retrospective review of a single institution/single surgeon experience of complex ventral hernia repair performed over a 5-year period. Patients were classified into different hernia types based on their characteristics and underwent hernia repair according to the presented algorithm. RESULTS: A total of 133 patients underwent a complex ventral hernia repair between January 2005 and September 2009. The separation of components technique was used in the majority of cases. Permanent or biologic mesh was added in select patients. Adjunctive procedures were performed as indicated. The majority of short-term (less than 1 year) recurrences occurred in patients expected to have impaired wound healing due to comorbid conditions. In these patients, the recurrence rate was reduced when autologous repair was reinforced with mesh. CONCLUSION: Autologous tissue is the preferred method for reconstruction of complex ventral hernias. In certain instances, such as contamination, use of an acellular dermal matrix mesh is added as a temporizing measure. A subset of patients who will be prone to recurrence remains. Long-term follow-up is needed to confirm reliable and reproducible results.

Authors
Hadeed, JG; Walsh, MD; Pappas, TN; Pestana, IA; Tyler, DS; Levinson, H; Mantyh, C; Jacobs, DO; Lagoo-Deenadalayan, SA; Erdmann, D
MLA Citation
Hadeed, JG, Walsh, MD, Pappas, TN, Pestana, IA, Tyler, DS, Levinson, H, Mantyh, C, Jacobs, DO, Lagoo-Deenadalayan, SA, and Erdmann, D. "Complex abdominal wall hernias: a new classification system and approach to management based on review of 133 consecutive patients." Ann Plast Surg 66.5 (May 2011): 497-503.
PMID
21451375
Source
pubmed
Published In
Annals of Plastic Surgery
Volume
66
Issue
5
Publish Date
2011
Start Page
497
End Page
503
DOI
10.1097/SAP.0b013e3182145387

Colonic arteriovenous malformations

Arteriovenous malformations (also known as angiodysplasias, vascular ectasias, or angiomas) are defined as degenerative lesions of the gastrointestinal tract that result from chronic obstruction of the submucosal veins. Even though the etiology of these lesions is not well understood, a leading hypothesis is that peristaltic contractions of the muscular layers lead to chronic partial obstruction of submucosal veins of the intestinal wall and with time these veins become dilated and tortuous. © 2010 Springer-Verlag New York.

Authors
De La Fuente, SG; Mantyh, CR
MLA Citation
De La Fuente, SG, and Mantyh, CR. "Colonic arteriovenous malformations." Gastrointestinal Bleeding: A Practical Approach to Diagnosis and Management. December 1, 2010. 155-161.
Source
scopus
Publish Date
2010
Start Page
155
End Page
161
DOI
10.1007/978-1-4419-1693-8_14

Bleeding colonic tumors

Bleeding colonic tumors represent one of many causes of lower gastrointestinal bleeding (LGIB) and may present acutely or chronically. The evaluation and management LGIB as a whole is discussed elsewhere in this text. This chapter will focus on the etiology, work-up, and treatment of bleeding colonic tumors. © 2010 Springer-Verlag New York.

Authors
Olcese, VA; Mantyh, CR
MLA Citation
Olcese, VA, and Mantyh, CR. "Bleeding colonic tumors." Gastrointestinal Bleeding: A Practical Approach to Diagnosis and Management. December 1, 2010. 163-171.
Source
scopus
Publish Date
2010
Start Page
163
End Page
171
DOI
10.1007/978-1-4419-1693-8_15

A safety and survival analysis of neoadjuvant bevacizumab with standard chemoradiation in a phase I/II study compared with standard chemoradiation in locally advanced rectal cancer.

INTRODUCTION: Bevacizumab is increasingly being tested with neoadjuvant regimens in patients with localized cancer, but its effects on metastasis and survival remain unknown. This study examines the long-term outcome of clinical stage II/III rectal cancer patients treated in a prospective phase II study of bevacizumab with chemoradiation and surgery. As a benchmark, we used data from an analysis of 42 patients with locally advanced rectal cancer treated with a contemporary approach of preoperative fluoropyrimidine-based radiation therapy. MATERIALS AND METHODS: Outcome analyses were performed on 32 patients treated prospectively with neoadjuvant bevacizumab, 5-fluorouracil, radiation therapy, and surgery as well as 42 patients treated with standard fluoropyrimidine-based chemoradiation. RESULTS: Overall survival, disease-free survival, and local control showed favorable trends in patients treated with bevacizumab with chemoradiation followed by surgery. Acute and postoperative toxicity appeared acceptable. CONCLUSIONS: Neoadjuvant bevacizumab with standard chemoradiation and surgery shows promising long-term efficacy and safety profiles in locally advanced rectal cancer patients.

Authors
Willett, CG; Duda, DG; Ancukiewicz, M; Shah, M; Czito, BG; Bentley, R; Poleski, M; Fujita, H; Lauwers, GY; Carroll, M; Tyler, D; Mantyh, C; Shellito, P; Chung, DC; Clark, JW; Jain, RK
MLA Citation
Willett, CG, Duda, DG, Ancukiewicz, M, Shah, M, Czito, BG, Bentley, R, Poleski, M, Fujita, H, Lauwers, GY, Carroll, M, Tyler, D, Mantyh, C, Shellito, P, Chung, DC, Clark, JW, and Jain, RK. "A safety and survival analysis of neoadjuvant bevacizumab with standard chemoradiation in a phase I/II study compared with standard chemoradiation in locally advanced rectal cancer." Oncologist 15.8 (2010): 845-851.
PMID
20667969
Source
pubmed
Published In
The oncologist
Volume
15
Issue
8
Publish Date
2010
Start Page
845
End Page
851
DOI
10.1634/theoncologist.2010-0030

Plasma soluble VEGFR-1 is a potential dual biomarker of response and toxicity for bevacizumab with chemoradiation in locally advanced rectal cancer.

We explored plasma and urinary concentrations of two members of the vascular endothelial growth factor (VEGF) family and their receptors as potential response and toxicity biomarkers of bevacizumab with neoadjuvant chemoradiation in patients with localized rectal cancer. The concentrations of VEGF, placental growth factor (PlGF), soluble VEGF receptor 1 (sVEGFR-1), and sVEGFR-2 were measured in plasma and urine at baseline and during treatment. Pretreatment values and changes over time were analyzed as potential biomarkers of pathological response to treatment as well as for acute toxicity in patients with locally advanced rectal cancer treated prospectively in 2002-2008 with neoadjuvant bevacizumab, 5-fluorouracil, radiation therapy, and surgery in a phase I/II trial. Of all biomarkers, pretreatment plasma sVEGFR-1-an endogenous blocker of VEGF and PlGF, and a factor linked with "vascular normalization"-was associated with both primary tumor regression and the development of adverse events after neoadjuvant bevacizumab and chemoradiation. Based on the findings in this exploratory study, we propose that plasma sVEGFR-1 should be further studied as a potential biomarker to stratify patients in future studies of bevacizumab and/or cytotoxics in the neoadjuvant setting.

Authors
Duda, DG; Willett, CG; Ancukiewicz, M; di Tomaso, E; Shah, M; Czito, BG; Bentley, R; Poleski, M; Lauwers, GY; Carroll, M; Tyler, D; Mantyh, C; Shellito, P; Clark, JW; Jain, RK
MLA Citation
Duda, DG, Willett, CG, Ancukiewicz, M, di Tomaso, E, Shah, M, Czito, BG, Bentley, R, Poleski, M, Lauwers, GY, Carroll, M, Tyler, D, Mantyh, C, Shellito, P, Clark, JW, and Jain, RK. "Plasma soluble VEGFR-1 is a potential dual biomarker of response and toxicity for bevacizumab with chemoradiation in locally advanced rectal cancer." Oncologist 15.6 (2010): 577-583.
PMID
20484123
Source
pubmed
Published In
The oncologist
Volume
15
Issue
6
Publish Date
2010
Start Page
577
End Page
583
DOI
10.1634/theoncologist.2010-0029

Extrinsic surgical denervation ameliorates TNBS-induced colitis in rats.

BACKGROUND/AIMS: Neurogenic inflammation refers to an inflammatory reflex arc by sensory neurons which transmit nocious stimulus centrally and results in both pain perception and intense local inflammatory reaction. Specific neurons, receptors, and their respective neurotransmitters have been studied in numerous organ systems including the gastrointestinal tract. Neurogenic inflammation has been suggested to play a key role in the pathogenesis of inflammatory bowel disease. In this study, we studied the effect of surgical denervation of specific somatosensory neurons in a well-established animal model of colitis. METHODOLOGY: Adult male rats were underwent surgical denervation around the inferior mesenteric artery or sham operation. After ten days trinitrobenzene sulfonic acid (TNBS) or vehicle was administered by enema. Inflammation was assessed by, histological evaluation, macroscopic damage score, myeloperoxidase (MPO) activity, and substance P receptor immunoreactivity (SPRIR). RESULTS: Compared with sham operation with TNBS administration, surgical denervation with TNBS administration suppressed the score in all of the inflammatory indices and had almost no signs of inflammation in histological evaluation. CONCLUSIONS: Surgical denervation has a protective effect on TNBS-induced colitis in rats. Thus, sensory neurons play a key role in the pathogenesis of inflammation in this well-established model of acute colitis.

Authors
Takami, Y; Mantyh, CR; Pappas, TN; Takahashi, T; Koda, K; Miyazaki, M
MLA Citation
Takami, Y, Mantyh, CR, Pappas, TN, Takahashi, T, Koda, K, and Miyazaki, M. "Extrinsic surgical denervation ameliorates TNBS-induced colitis in rats." Hepatogastroenterology 56.91-92 (May 2009): 682-686.
PMID
19621680
Source
pubmed
Published In
Hepato-gastroenterology
Volume
56
Issue
91-92
Publish Date
2009
Start Page
682
End Page
686

Neoadjuvant chemoradiation for rectal cancer reduces lymph node harvest in proctectomy specimens.

PURPOSE: The purpose of this study was to compare the number of lymph nodes retrieved following proctectomy for rectal cancer in patients either receiving no neoadjuvant therapy versus those treated with standard preoperative chemoradiation. METHODS: A retrospective review was performed of all consecutive patients that underwent proctectomy for rectal cancer from 1997-2006. Specimens from patients that received neoadjuvant therapy were compared to patients that did not receive preoperative chemoradiation. RESULTS: Of a total of 286 patients, 188 received neoadjuvant therapy and 88 did not. More patients with stage II or higher cancers received neoadjuvant therapy. Overall, fewer neoadjuvant patients underwent an anastomotic procedure than the no neoadjuvant group (17% vs. 7% APR). Significantly fewer total lymph nodes were retrieved in the neoadjuvant therapy patients compared to those who did not receive preoperatively therapy (Neo 14.6 +/- 0.6 vs. No-Neo 17.2 +/- 1.1, p < 0.029). CONCLUSIONS: Standard neoadjuvant therapy significantly decreases the number of lymph nodes retrieved following proctectomy for patients with rectal cancers. Quality initiatives or performance measures evaluating lymph node harvest following proctectomy should reflect the use of preoperative chemoradiation.

Authors
de la Fuente, SG; Manson, RJ; Ludwig, KA; Mantyh, CR
MLA Citation
de la Fuente, SG, Manson, RJ, Ludwig, KA, and Mantyh, CR. "Neoadjuvant chemoradiation for rectal cancer reduces lymph node harvest in proctectomy specimens." J Gastrointest Surg 13.2 (February 2009): 269-274.
PMID
18850250
Source
pubmed
Published In
Journal of Gastrointestinal Surgery
Volume
13
Issue
2
Publish Date
2009
Start Page
269
End Page
274
DOI
10.1007/s11605-008-0717-2

Endogenous ghrelin and 5-HT regulate interdigestive gastrointestinal contractions in conscious rats.

Endogenous ghrelin causes interdigestive contractions of the stomach in rats. In contrast, previous studies showed that 5-HT(3) and 5-HT(4) receptors were involved in regulating intestinal interdigestive contractions. We studied the possible role of endogenous ghrelin and 5-HT regulating interdigestive gastrointestinal (GI) contractions in rats. Four strain gauge transducers were implanted on the antrum, duodenum, and proximal and distal jejunum. After an overnight fast, GI contractions were recorded in freely moving conscious rats and ghrelin receptor antagonists [(d-lys3)GHRP6; 1 micromol/kg], 5-HT(3) antagonists (Ondansetron; 0.5 mg/kg) and 5-HT(4) antagonists (GR 125,487; 1 mg/kg) were administered (bolus iv). To evaluate the relationship between the luminal concentrations of 5-HT and phase III-like contractions of the duodenum, duodenal juice was collected via the intraduodenal catheter. 5-HT content of the duodenal juice was measured by HPLC. (d-lys3)GHRP6 significantly attenuated the occurrence and amplitude of phase III-like contractions of the antrum, but not the duodenum and jejunum. 5-HT(4) antagonists significantly reduced spontaneous phase III-like contractions of the jejunum, without affecting those of the antrum and duodenum. In contrast, 5-HT(3) antagonists did not affect phase III-like contractions in GI tract. Luminal concentration of 5-HT at the phase III-like contraction (36.0 +/- 13.3 ng/ml, n = 9) was significantly higher than that at the phase I-like contractions of the duodenum (4.9 +/- 1.6 ng/ml, n = 9, P < 0.05). It is suggested that released ghrelin from the gastric mucosa mediates gastric phase III-like contractions, whereas 5-HT released from enterochromaffin cells of the duodenal mucosa mediates intestinal phase III-like contractions via 5-HT(4) receptors.

Authors
Taniguchi, H; Ariga, H; Zheng, J; Ludwig, K; Mantyh, C; Pappas, TN; Takahashi, T
MLA Citation
Taniguchi, H, Ariga, H, Zheng, J, Ludwig, K, Mantyh, C, Pappas, TN, and Takahashi, T. "Endogenous ghrelin and 5-HT regulate interdigestive gastrointestinal contractions in conscious rats." Am J Physiol Gastrointest Liver Physiol 295.2 (August 2008): G403-G411.
PMID
18566321
Source
pubmed
Published In
American journal of physiology. Gastrointestinal and liver physiology
Volume
295
Issue
2
Publish Date
2008
Start Page
G403
End Page
G411
DOI
10.1152/ajpgi.90260.2008

Routine contrast imaging of low pelvic anastomosis prior to closure of defunctioning ileostomy: is it necessary?

PURPOSE: The purpose of the study was to determine the utility of routine contrast enema prior to ileostomy closure and its impact on patient management in patients with a low pelvic anastomosis. MATERIAL AND METHODS: Two hundred eleven patients had a temporary loop ileostomy constructed to protect a low colorectal or coloanal anastomosis following low anterior resection for cancer (57%) or other disease (12%) or to protect an ileal pouch-anal anastomosis following restorative proctocolectomy (31%). All patients were evaluated by physical examination, proctoscopy, and water-soluble contrast enema prior to ileostomy closure. Imaging results were correlated with the clinical situation to determine the effects on patient management. RESULTS: The mean time from ileostomy creation to closure was 15.6 weeks. Overall, 203 patients (96%) had an uncomplicated course. Eight patients (4%) developed an anastomotic leak, seven of which were diagnosed clinically and confirmed radiographically before planned ileostomy closure. Resolution of the leak was confirmed by follow-up contrast enema. One patient, whose pouchogram revealed a normal anastomosis, clinically developed a leak after ileostomy closure. It is important to note that routine contrast enema examination did not reveal an anastomotic leak or stricture that was not already suspected clinically. CONCLUSIONS: All patients who developed an anastomotic leak in this study were diagnosed clinically, and the diagnosis was confirmed by selective use of radiographic tests. Routine contrast enema evaluation of low pelvic anastomoses before loop ileostomy closure did not provide any additional information that changed patient management. The utility of this routine practice should be questioned.

Authors
Kalady, MF; Mantyh, CR; Petrofski, J; Ludwig, KA
MLA Citation
Kalady, MF, Mantyh, CR, Petrofski, J, and Ludwig, KA. "Routine contrast imaging of low pelvic anastomosis prior to closure of defunctioning ileostomy: is it necessary?." J Gastrointest Surg 12.7 (July 2008): 1227-1231.
PMID
18368457
Source
pubmed
Published In
Journal of Gastrointestinal Surgery
Volume
12
Issue
7
Publish Date
2008
Start Page
1227
End Page
1231
DOI
10.1007/s11605-008-0510-2

Does ghrelin explain accelerated gastric emptying in the early stages of diabetes mellitus?

During the early stages of diabetes, gastric emptying is often accelerated, rather than delayed. The mechanism of accelerated gastric emptying in diabetes has not been fully studied. A recent study showed that plasma ghrelin levels were elevated in diabetes. As postprandial antropyloric coordination plays an important role in mediating solid gastric emptying, we hypothesize that the elevated plasma ghrelin levels increase postprandial antropyloric coordination to accelerate emptying in the early stages of diabetes. To test this hypothesis, rats were made diabetic by streptozotocin (STZ; 50 mg/kg) injection, and, 2 wk later, pre- and postprandial plasma ghrelin levels, antropyloric coordination, and solid gastric emptying were determined. In control rats, plasma ghrelin levels were immediately reduced after feeding. In contrast, plasma ghrelin levels remained within the fasted levels in STZ rats after feeding. In STZ rats, gastric emptying was significantly accelerated (77.4 +/- 3.2%, n = 6), compared with that of control rats (58.8 +/- 2.5%, n = 6, P < 0.05). Treatments with anti-ghrelin antibodies attenuated accelerated gastric emptying in STZ rats (50.1 +/- 3.5%, n = 6, P < 0.05), while having little effect in vehicle control rats. The incidence of postprandial antropyloric coordination was significantly increased in STZ rats, compared with that of control rats (P < 0.05). Treatments with anti-ghrelin antibodies suppressed this enhanced antropyloric coordination in STZ rats. Our study suggests that elevated endogenous ghrelin enhances antropyloric coordination, which accelerates gastric emptying in the early stages of diabetes.

Authors
Ariga, H; Imai, K; Chen, C; Mantyh, C; Pappas, TN; Takahashi, T
MLA Citation
Ariga, H, Imai, K, Chen, C, Mantyh, C, Pappas, TN, and Takahashi, T. "Does ghrelin explain accelerated gastric emptying in the early stages of diabetes mellitus?." Am J Physiol Regul Integr Comp Physiol 294.6 (June 2008): R1807-R1812.
PMID
18385464
Source
pubmed
Published In
American journal of physiology. Regulatory, integrative and comparative physiology
Volume
294
Issue
6
Publish Date
2008
Start Page
R1807
End Page
R1812
DOI
10.1152/ajpregu.00785.2007

Surgical autonomic denervation results in altered colonic motility: an explanation for low anterior resection syndrome?

BACKGROUND: We hypothesized that the bowel dysfunction known as low anterior resection syndrome is caused by denervation of the left colon. The purpose of this study is to determine how surgical denervation changes left colon motility and to identify the mechanism of this change. MATERIALS AND METHODS: Strain gauge transducers were implanted on the serosal surface of the descending colon of male SD rats (250-300 g). After a 2-h baseline recording, motility was recorded for another 2 h after either simple left colon manipulation (n = 6) or surgical left colon denervation (n = 6). Various pharmacologic agents were then administered before denervation to determine the mechanism by which denervation changed left colon motility. Changes in motility were calculated by determining a % motility index (MI) (%MI = MI posttreatment/MI baseline) with significance defined as P < .05. RESULT: Denervation resulted in an increased mean %MI (128.8 +/- 15.4) compared with simple manipulation of the bowel, which decreased mean %MI (87.9 +/- 25.3) (P < .05). In the second set of experiments, both guanethidine and phentolamine increased mean %MI after injection (P < .05), but no additional increase of %MI occurred after denervation (P < .05). However, propranolol produced no increase of motility after injection and it did not affect the increase in motility observed after denervation (P < .05). CONCLUSION: Surgical denervation of the left colon results in a significant increase in motility. Pharmacologically, this increase seems to be the result of destruction of an inhibitory alpha-sympathetic pathway. This increased motility may contribute to low anterior resection syndrome.

Authors
Lee, WY; Takahashi, T; Pappas, T; Mantyh, CR; Ludwig, KA
MLA Citation
Lee, WY, Takahashi, T, Pappas, T, Mantyh, CR, and Ludwig, KA. "Surgical autonomic denervation results in altered colonic motility: an explanation for low anterior resection syndrome?." Surgery 143.6 (June 2008): 778-783.
PMID
18549894
Source
pubmed
Published In
Surgery
Volume
143
Issue
6
Publish Date
2008
Start Page
778
End Page
783
DOI
10.1016/j.surg.2008.03.014

Daily intake of high dietary fiber slows accelerated colonic transit induced by restrain stress in rats.

BACKGROUND: Stress and central corticotropin releasing factor (CRF) are contributing factors to the pathogenesis of irritable bowel syndrome (IBS). It has been shown that restraint stress and central CRF stimulate colonic motility in rats. Short-chain fatty acids (SCFAs) are produced by bacterial fermentation from dietary fibers. It is controversial whether daily intake of dietary fiber is beneficial for patients with diarrhea-predominant IBS. We studied whether dietary fiber intake affects colonic transit and motility stimulated by restraint stress and central CRF in rats. METHODS: Corn starch is digested almost completely in the small intestine, while potato starch shows substantial resistance to alpha-amylase and its consumption leads to stimulation of large-bowel fermentation. Four weeks after a corn starch, potato starch, or usual diet (rat chow), colonic transit and motility stimulated by restraint stress and intracisternal (ic) injection of CRF were studied. Fecal concentration of SCFAs in the cecum was measured by high-performance liquid chromatography (HPLC). RESULTS: Four-week treatment with potato starch diet significantly increased cecal concentrations of SCFAs, compared to treatment with corn starch diet. Accelerated colonic transit induced by stress and ic injection of CRF (1 microg) were significantly attenuated in rats receiving potato starch diet compared to rats receiving corn starch diet. The incidence of unformed stool (diarrhea) induced by stress and CRF was also reduced in rats receiving potato starch diet compared to rats receiving corn starch diet and usual diet. CONCLUSION: It is suggested that daily intake of a high-fiber diet may prevent stress- and CRF-induced acceleration of colonic transit and diarrhea. This study may contribute to treatment for the patients of diarrhea-predominant IBS.

Authors
Takahashi, T; Nakade, Y; Fukuda, H; Tsukamoto, K; Mantyh, C; Pappas, TN
MLA Citation
Takahashi, T, Nakade, Y, Fukuda, H, Tsukamoto, K, Mantyh, C, and Pappas, TN. "Daily intake of high dietary fiber slows accelerated colonic transit induced by restrain stress in rats." Dig Dis Sci 53.5 (May 2008): 1271-1277.
PMID
18335315
Source
pubmed
Published In
Digestive Diseases and Sciences
Volume
53
Issue
5
Publish Date
2008
Start Page
1271
End Page
1277
DOI
10.1007/s10620-008-0228-8

Gastroduodenal interdigestive phase III-Like contractions are mediated via ghrelin, while intestinal interdigestive phase III-Like contractions are mediated via 5-HT in conscious rats

Authors
Taniguchi, H; Ariga, H; Chen, C; Zheng, J; Ludwig, KA; Mantyh, CR; Pappas, TN; Takahashi, T
MLA Citation
Taniguchi, H, Ariga, H, Chen, C, Zheng, J, Ludwig, KA, Mantyh, CR, Pappas, TN, and Takahashi, T. "Gastroduodenal interdigestive phase III-Like contractions are mediated via ghrelin, while intestinal interdigestive phase III-Like contractions are mediated via 5-HT in conscious rats." April 2008.
Source
wos-lite
Published In
Gastroenterology
Volume
134
Issue
4
Publish Date
2008
Start Page
A686
End Page
A686

Acoustic stress attenuates gastric migrating motor complex, without affecting motilin release, via inhibiting sympatho-vagal balance in conscious dogs

Authors
Nakajima, H; Taniguchi, H; Imai, K; Ariga, H; Ludwig, KA; Mantyh, CR; Pappas, TN; Takahashi, T
MLA Citation
Nakajima, H, Taniguchi, H, Imai, K, Ariga, H, Ludwig, KA, Mantyh, CR, Pappas, TN, and Takahashi, T. "Acoustic stress attenuates gastric migrating motor complex, without affecting motilin release, via inhibiting sympatho-vagal balance in conscious dogs." April 2008.
Source
wos-lite
Published In
Gastroenterology
Volume
134
Issue
4
Publish Date
2008
Start Page
A538
End Page
A538

Plasma insulin, but not glucose, inhibits ghrelin release in vascularly isolated perfused rat stomach ex-vivo; a possible mechanism of increased plasma ghrelin levels in diabetes

Authors
Ariga, H; Tsukamoto, K; Taniguchi, H; Mantyh, CR; Pappas, TN; Takahashi, T
MLA Citation
Ariga, H, Tsukamoto, K, Taniguchi, H, Mantyh, CR, Pappas, TN, and Takahashi, T. "Plasma insulin, but not glucose, inhibits ghrelin release in vascularly isolated perfused rat stomach ex-vivo; a possible mechanism of increased plasma ghrelin levels in diabetes." April 2008.
Source
wos-lite
Published In
Gastroenterology
Volume
134
Issue
4
Publish Date
2008
Start Page
A533
End Page
A533

Eating behavior modulates ghrelin surge, resulting in potent interdigestive gastric contractions and acceleration of gastric emptying in rats

Authors
Ariga, H; Imai, K; Chen, C; Mantyh, CR; Pappas, TN; Takahashi, T
MLA Citation
Ariga, H, Imai, K, Chen, C, Mantyh, CR, Pappas, TN, and Takahashi, T. "Eating behavior modulates ghrelin surge, resulting in potent interdigestive gastric contractions and acceleration of gastric emptying in rats." April 2008.
Source
wos-lite
Published In
Gastroenterology
Volume
134
Issue
4
Publish Date
2008
Start Page
A284
End Page
A284

Interdigestive migrating motor complex is regulated by the interaction between motilin and 5-HT of the duodenal mucosa in conscious dogs

Authors
Nakajima, H; Mochiki, E; Taniguchi, H; Ariga, H; Chen, C; Ludwig, KA; Mantyh, CR; Pappas, TN; Takahashi, T
MLA Citation
Nakajima, H, Mochiki, E, Taniguchi, H, Ariga, H, Chen, C, Ludwig, KA, Mantyh, CR, Pappas, TN, and Takahashi, T. "Interdigestive migrating motor complex is regulated by the interaction between motilin and 5-HT of the duodenal mucosa in conscious dogs." April 2008.
Source
wos-lite
Published In
Gastroenterology
Volume
134
Issue
4
Publish Date
2008
Start Page
A689
End Page
A689

Time course of gastric emptying, plasma ghrelin levels and autonomic nerves function in the chronic stage of diabetes in rats

Authors
Ariga, H; Imai, K; Ludwig, KA; Mantyh, CR; Pappas, TN; Takahashi, T
MLA Citation
Ariga, H, Imai, K, Ludwig, KA, Mantyh, CR, Pappas, TN, and Takahashi, T. "Time course of gastric emptying, plasma ghrelin levels and autonomic nerves function in the chronic stage of diabetes in rats." April 2008.
Source
wos-lite
Published In
Gastroenterology
Volume
134
Issue
4
Publish Date
2008
Start Page
A395
End Page
A395

Fixed feeding potentiates interdigestive gastric motor activity in rats: importance of eating habits for maintaining interdigestive MMC.

Endogenous ghrelin regulates the occurrence of interdigestive gastric phase III-like contractions in rats. However, the fasted motor pattern is not as regular and potent in humans and dogs. We hypothesize that eating habits play an important role in maintaining a regular interdigestive gastric contractions. We studied the effect of fixed-feeding regimen on interdigestive gastric contractions and plasma acyl ghrelin levels. The fixed-fed rats were trained to the assigned meal feeding regimen, once daily at 12:00 PM to 4:00 PM for 14 days. Free-fed rats were maintained with free access to food. As ghrelin regulates gastric emptying as well, solid gastric emptying was also studied in fixed-fed rats and free-fed rats. In free-fed rats, two of six rats did not show interdigestive gastric phase III-like contractions. In contrast, phase III-like contractions were observed in all rats 14 days after starting the fixed-feeding regimen. The maximal amplitude of phase III-like contractions significantly increased from 8.4 +/- 0.6 to 16.3 +/- 1.8 g (n = 6, P < 0.05) 14 days after the start of the fixed feeding. Fasted and postprandial plasma ghrelin levels were significantly increased after 14 days of fixed feeding. Solid gastric emptying was significantly accelerated in fixed-fed rats (72.1 +/- 4.2%) compared with that of free-fed rats (58.7 +/- 2.7%, n = 6, P < 0.05). Our present findings suggest that fixed feeding increases plasma ghrelin levels, potent interdigestive contractions, and acceleration of gastric emptying.

Authors
Ariga, H; Imai, K; Chen, C; Mantyh, C; Pappas, TN; Takahashi, T
MLA Citation
Ariga, H, Imai, K, Chen, C, Mantyh, C, Pappas, TN, and Takahashi, T. "Fixed feeding potentiates interdigestive gastric motor activity in rats: importance of eating habits for maintaining interdigestive MMC." Am J Physiol Gastrointest Liver Physiol 294.3 (March 2008): G655-G659.
PMID
18174270
Source
pubmed
Published In
American journal of physiology. Gastrointestinal and liver physiology
Volume
294
Issue
3
Publish Date
2008
Start Page
G655
End Page
G659
DOI
10.1152/ajpgi.00484.2007

Effects of electroacupuncture on gastric motility and heart rate variability in conscious rats.

To clarify the mechanism of site-specific effects of acupuncture on gastric motor function, we studied the simultaneous recording of gastric motility and electrocardiogram (ECG) for heart rate variability (HRV) analysis in conscious rats. Gastric motility and ECG were recorded before, during and after electroacupuncture (EA) at ST-36 (hind limb) or ST-25 (abdomen). EA at ST-36 significantly increased gastric motility and decreased the ratio of low frequency (LF)/high frequency (HF) of the HRV analysis. In contrast, EA at ST-25 significantly inhibited gastric motility and increased LF/HF ratio. There was a significant correlation observed between the changes of gastric motility and LF/HF ratio in response to EA. It is suggested that the stimulatory effect of EA at ST-36 on gastric motility is associated with its stimulatory effect on vagal activity. The inhibitory effect of EA at ST-25 on gastric motility is associated with its stimulatory effect on the sympathetic nerve activity.

Authors
Imai, K; Ariga, H; Chen, C; Mantyh, C; Pappas, TN; Takahashi, T
MLA Citation
Imai, K, Ariga, H, Chen, C, Mantyh, C, Pappas, TN, and Takahashi, T. "Effects of electroacupuncture on gastric motility and heart rate variability in conscious rats." Auton Neurosci 138.1-2 (February 29, 2008): 91-98.
PMID
18083640
Source
pubmed
Published In
Autonomic Neuroscience: Basic and Clinical
Volume
138
Issue
1-2
Publish Date
2008
Start Page
91
End Page
98
DOI
10.1016/j.autneu.2007.11.003

Ghrelin accelerates gastric emptying via early manifestation of antro-pyloric coordination in conscious rats.

Ghrelin is known to enhance gastric motility and accelerate gastric emptying of liquid and solid food in rats. As solid gastric emptying is regulated by the coordinated motor pattern between the antrum and pylorus (antro-pyloric coordination), we studied the correlation between solid gastric emptying and antro-pyloric coordination in response to ghrelin. Rats were given 1.5 g of solid food after a 24-h fasting. Immediately after the ingestion, ghrelin (0.4-8.0 microg/kg) or saline was administered by intraperitoneal (i.p.) injection. Ninety minutes after the feeding, rats were euthanized and gastric content was removed to calculate gastric emptying. To evaluate the antro-pyloric coordination, strain gauge transducers were sutured on the antrum and pylorus. The incidence of postprandial antro-pyloric coordination was compared between ghrelin-and saline-injected rats. In saline-injected rats, gastric emptying was 58.3+/-3.7% (n=6). Ghrelin (4.0-8.0 microg/kg), accelerated gastric emptying. Maximum effect was obtained by ghrelin (4.0 microg/kg), which significantly accelerated gastric emptying to 77.4+/-3.7% (n=6, p<0.05). The number of antro-pyloric coordination 20-40 min after feeding was significantly increased in ghrelin-injected rats, compared to that of saline-injected rats (n=4, p<0.05). It is suggested that enhanced antro-pyloric coordination play an important role in accelerated solid gastric emptying induced by ghrelin.

Authors
Ariga, H; Nakade, Y; Tsukamoto, K; Imai, K; Chen, C; Mantyh, C; Pappas, TN; Takahashi, T
MLA Citation
Ariga, H, Nakade, Y, Tsukamoto, K, Imai, K, Chen, C, Mantyh, C, Pappas, TN, and Takahashi, T. "Ghrelin accelerates gastric emptying via early manifestation of antro-pyloric coordination in conscious rats." Regul Pept 146.1-3 (February 7, 2008): 112-116.
PMID
17913258
Source
pubmed
Published In
Regulatory Peptides
Volume
146
Issue
1-3
Publish Date
2008
Start Page
112
End Page
116
DOI
10.1016/j.regpep.2007.08.022

Outcomes Review of Reconstructive Techniques Following Proctectomy

Surgery continues to be essential in the management of colorectal tumors. For patients with mid and low rectal tumors, sphincter-preserving techniques have become increasingly common and acceptable oncologic results can be achieved. In general, straight coloanal anastomoses are associated with relatively poor postoperative bowel function due to the loss of the rectal reservoir. To overcome this limitation, colonic reservoirs, such as the colonic J-pouch or transverse coloplasty have been developed. Over the last several years, a significant number of trials have been published in the surgical literature comparing these techniques. This manuscript describes the basis of the functionality outcomes following restoration of intestinal continuity after protectomy for colorectal cancer. © 2008 Elsevier Inc. All rights reserved.

Authors
Fuente, SGDL; Mantyh, CR
MLA Citation
Fuente, SGDL, and Mantyh, CR. "Outcomes Review of Reconstructive Techniques Following Proctectomy." Seminars in Colon and Rectal Surgery 19.1 (2008): 41-47.
Source
scival
Published In
Seminars in Colon and Rectal Surgery
Volume
19
Issue
1
Publish Date
2008
Start Page
41
End Page
47
DOI
10.1053/j.scrs.2008.01.009

Simultaneous resections of colorectal cancer and synchronous liver metastases: a multi-institutional analysis.

BACKGROUND: The safety of simultaneous resections of colorectal cancer and synchronous liver metastases (SCRLM) is not established. This multi-institutional retrospective study compared postoperative outcomes after simultaneous and staged colorectal and hepatic resections. METHODS: Clinicopathologic data, treatments, and postoperative outcomes from patients who underwent simultaneous or staged colorectal and hepatic resections at three hepatobiliary centers from 1985-2006 were reviewed. RESULTS: 610 patients underwent simultaneous (n = 135) or staged (n = 475) resections of colorectal cancer and SCRLM. Seventy staged patients underwent colorectal and hepatic resections at the same institution. Simultaneous patients had fewer (median 1 versus 2) and smaller (median 2.5 versus 3.5 cm) metastases and less often underwent major (> or = three segments) hepatectomy (26.7% versus 61.3%, p < 0.05). Combined hospital stay was lower after simultaneous resections (median 8.5 versus 14 days, p < 0.0001). Mortality (1.0% versus 0.5%) and severe morbidity (14.1% versus 12.5%) were similar after simultaneous colorectal resection and minor hepatectomy compared with isolated minor hepatectomy (both p > 0.05). For major hepatectomy, simultaneous colorectal resection increased mortality (8.3% versus 1.4%, p < 0.05) and severe morbidity (36.1% versus 15.1%, p < 0.05). Combined severe morbidity after staged resections was lower compared to simultaneous resections (36.1% versus 17.6%, p = 0.05) for major hepatectomy but similar for minor hepatectomy (14.1% versus 10.5%, p > 0.05). Major hepatectomy independently predicted severe morbidity after simultaneous resections [hazard ratio (HR) = 3.4, p = 0.008]. CONCLUSIONS: Simultaneous colorectal and minor hepatic resections are safe and should be performed for most patients with SCRLM. Due to increased risk of severe morbidity, caution should be exercised before performing simultaneous colorectal and major hepatic resections.

Authors
Reddy, SK; Pawlik, TM; Zorzi, D; Gleisner, AL; Ribero, D; Assumpcao, L; Barbas, AS; Abdalla, EK; Choti, MA; Vauthey, J-N; Ludwig, KA; Mantyh, CR; Morse, MA; Clary, BM
MLA Citation
Reddy, SK, Pawlik, TM, Zorzi, D, Gleisner, AL, Ribero, D, Assumpcao, L, Barbas, AS, Abdalla, EK, Choti, MA, Vauthey, J-N, Ludwig, KA, Mantyh, CR, Morse, MA, and Clary, BM. "Simultaneous resections of colorectal cancer and synchronous liver metastases: a multi-institutional analysis." Ann Surg Oncol 14.12 (December 2007): 3481-3491.
PMID
17805933
Source
pubmed
Published In
Annals of Surgical Oncology
Volume
14
Issue
12
Publish Date
2007
Start Page
3481
End Page
3491
DOI
10.1245/s10434-007-9522-5

Assessing the quality of colorectal cancer care: do we have appropriate quality measures? (A systematic review of literature).

RATIONALE, AIMS AND OBJECTIVES: The burden of illness from colorectal cancer (CRC) can be reduced by improving the quality of care. Identifying appropriate quality measures is the first step in this direction. We identified process measures currently available to assess the quality of diagnosis and management of CRC. We also evaluated the extent to which these measures are ready to be implemented in clinical practice, and identified areas for future research. METHODS: We searched MEDLINE, Cochrane Database of Systematic Reviews, and relevant grey literature. We identified 3771 abstracts and reviewed 74 articles that included quality measures for diagnosis or management of CRC. Measures from traditional quality improvement literature, and from epidemiological and other studies that included quality measures as part of their research agenda, were considered. In addition, we devised a summary rating scale (IST) to appraise the extent of a measure's importance and usability, scientific acceptability and extent of testing. RESULTS: The coverage of general process measures in CRC is extensive. Most measures are important, but need to be developed and field-tested. The best available measures relate to pathology and chemotherapy. No measures are available for assessing quality of management of stage IV rectal cancer and hepatic metastasis; chemotherapy for stage II colon cancer; and procedure notes. CONCLUSIONS: There is an urgent need to refine existing measures and to develop scientifically accurate quality measures for a comprehensive assessment of the quality of CRC care. The role of the federal government and professional societies is critical in pursuing this goal.

Authors
Patwardhan, M; Fisher, DA; Mantyh, CR; McCrory, DC; Morse, MA; Prosnitz, RG; Cline, K; Samsa, GP
MLA Citation
Patwardhan, M, Fisher, DA, Mantyh, CR, McCrory, DC, Morse, MA, Prosnitz, RG, Cline, K, and Samsa, GP. "Assessing the quality of colorectal cancer care: do we have appropriate quality measures? (A systematic review of literature)." J Eval Clin Pract 13.6 (December 2007): 831-845. (Review)
PMID
18070253
Source
pubmed
Published In
Journal of Evaluation in Clinical Practice
Volume
13
Issue
6
Publish Date
2007
Start Page
831
End Page
845
DOI
10.1111/j.1365-2753.2006.00762.x

Functional evaluation of the grafted wall with porcine-derived small intestinal submucosa (SIS) to a stomach defect in rats.

BACKGROUND: Small intestinal submucosa (SIS) represents a novel bio-scaffolding material that may be used to repair hollow-organ defects. However, it is unclear whether neurophysiologic responses return to SIS-grafted areas in the gut. We evaluated the functional recovery of a stomach defect grafted with the porcine-derived SIS. METHODS: Twelve rats had a full-thickness defect created in the stomach. SIS was secured to the gastric wall. After 6 months, muscle strips were harvested from within the grafted area to perform both a histologic and a functional study. Additional full-thickness muscle strips were harvested from the posterior in the same stomach as controls. A dose response curve was obtained with carbachol (CCH) or sodium nitroprusside (SNP). Activation of intrinsic nerves was achieved by electrical field stimulation (EFS). RESULTS: The response to CCH and amplitude in EFS showed tonic contraction in both controls and SIS strips in a concentration-dependent and frequency-dependent manner. The magnitude after each stimulation was significantly lower in SIS strips compared with controls (P < .01). However, the contraction ratio of EFS to ED(50) of CCH was not significantly different between the groups. Additionally, SNP produced relaxation in both strips in a concentration-dependent manner. Histologic findings revealed that an insufficient amount of smooth-muscle cells existed in the muscularis propria, whereas compensated growth was observed in the submucosa with nerve regeneration. CONCLUSIONS: This study demonstrates that SIS provides a template for nerve migration to the graft in the rodent stomach. Innervations showed a similar distribution to that observed in the controls. The clinical implications of such findings warrant additional investigation.

Authors
Ueno, T; de la Fuente, SG; Abdel-Wahab, OI; Takahashi, T; Gottfried, M; Harris, MB; Tatewaki, M; Uemura, K; Lawson, DC; Mantyh, CR; Pappas, TN
MLA Citation
Ueno, T, de la Fuente, SG, Abdel-Wahab, OI, Takahashi, T, Gottfried, M, Harris, MB, Tatewaki, M, Uemura, K, Lawson, DC, Mantyh, CR, and Pappas, TN. "Functional evaluation of the grafted wall with porcine-derived small intestinal submucosa (SIS) to a stomach defect in rats." Surgery 142.3 (September 2007): 376-383.
PMID
17723890
Source
pubmed
Published In
Surgery
Volume
142
Issue
3
Publish Date
2007
Start Page
376
End Page
383
DOI
10.1016/j.surg.2007.04.019

Sp1 regulates osteopontin expression in SW480 human colon adenocarcinoma cells.

BACKGROUND: Osteopontin (OPN) mediates cancer metastasis. Mechanisms regulating OPN expression in human colorectal cancer are unknown. Using SW480 colon adenocarcinoma cells, we hypothesized that transcription determines OPN expression. METHODS: SW480 constitutively express OPN. Transient transfection and deletion analysis of human OPN promoter (full-length 2.1 kb)-luciferase constructs identified cis-regulatory regions. Gelshift and chromatin immunoprecipitation (ChIP) assays identified the trans-regulatory nuclear protein. Using in vitro adhesion, migration, and invasion studies, siRNA was used to determine the functional effect of decreased nuclear protein expression. RESULTS: A cis-regulatory promoter region, nt-80 to nt-108, upregulated OPN transcription. Gelshift assays demonstrated specific binding of nuclear proteins. Competition with unlabeled mutant oligonucleotides indicated that the region, nt-94 to nt-104 (TGGGCTGGGC), was essential for protein binding in gelshift assays. Confirmatory ChIP assays showed the corresponding nuclear protein to be Sp1. Sp1 expression was ablated with siRNA (si-Sp1), resulting in decreased OPN-dependent adhesion, migration, and invasion by 50%, 70%, and 65%, respectively. Exogenous addition of OPN to si-Sp1 cells restored adhesion, migration, and invasion indices. CONCLUSIONS: In SW480 human colon cancer cells, we conclude that Sp1 mediated expression of the tumor metastasis protein, OPN, regulates in vitro functional correlates of tumor metastasis.

Authors
Takami, Y; Russell, MB; Gao, C; Mi, Z; Guo, H; Mantyh, CR; Kuo, PC
MLA Citation
Takami, Y, Russell, MB, Gao, C, Mi, Z, Guo, H, Mantyh, CR, and Kuo, PC. "Sp1 regulates osteopontin expression in SW480 human colon adenocarcinoma cells." Surgery 142.2 (August 2007): 163-169.
PMID
17689681
Source
pubmed
Published In
Surgery
Volume
142
Issue
2
Publish Date
2007
Start Page
163
End Page
169
DOI
10.1016/j.surg.2007.02.015

Reconstruction techniques after proctectomy: what's the best?

There are approximately 40,000 new rectal cancer cases diagnosed each year in the United States, representing the second most common gastrointestinal malignancy (behind colon cancer). With the advent of sphincter preserving techniques, patients with mid and low colorectal cancers enjoy the benefits of better postoperative functional outcomes and quality of life; however, controversy exists over which reconstructive technique is superior in restoring bowel continuity. Construction of a straight coloanal anastomosis is technically simpler, but functional outcomes are inferior compared with colonic reservoirs. The purpose of this review is to summarize the current data regarding reconstructive techniques following proctectomy.

Authors
de la Fuente, SG; Mantyh, CR
MLA Citation
de la Fuente, SG, and Mantyh, CR. "Reconstruction techniques after proctectomy: what's the best?." Clin Colon Rectal Surg 20.3 (August 2007): 221-230.
PMID
20011203
Source
pubmed
Published In
Clinics in Colon and Rectal Surgery
Volume
20
Issue
3
Publish Date
2007
Start Page
221
End Page
230
DOI
10.1055/s-2007-984866

Endogenous acyl ghrelin is involved in mediating spontaneous phase III-like contractions of the rat stomach.

In humans and dogs, it is known that motilin regulates phase III contractions of migrating motor complex (MMC) in the fasted state. In rats, however, motilin and its receptor have not been found, and administration of motilin failed to induce any phase III-like contractions. Ghrelin was discovered as the endogenous ligand for the growth hormone secretagogue receptor (GHS-R) from the rat stomach. Ghrelin promotes gastric premature phase III (phase III-like contractions) in the fasted state in rats. We hypothesized that endogenous ghrelin regulates spontaneous phase III-like contractions in rats. Strain gauge transducer was sutured on the antrum and a catheter was inserted into the jugular vein. We studied the effects of i.v. administration of ghrelin and a GHS-R antagonist on gastric phase III-like contractions in conscious rats. Plasma level of ghrelin was measured by a radioimmunoassay. Ghrelin augmented spontaneous phase III-like contractions and a GHS-R antagonist significantly attenuated the occurrence of spontaneous phase III-like contractions. During the phase I period, plasma ghrelin level increased to its peak then returned to basal level, subsequently phase III-like contractions were observed. These results suggest that endogenous ghrelin regulates gastric phase III-like contractions in rats.

Authors
Ariga, H; Tsukamoto, K; Chen, C; Mantyh, C; Pappas, TN; Takahashi, T
MLA Citation
Ariga, H, Tsukamoto, K, Chen, C, Mantyh, C, Pappas, TN, and Takahashi, T. "Endogenous acyl ghrelin is involved in mediating spontaneous phase III-like contractions of the rat stomach." Neurogastroenterol Motil 19.8 (August 2007): 675-680.
PMID
17640183
Source
pubmed
Published In
Neurogastroenterology & Motility
Volume
19
Issue
8
Publish Date
2007
Start Page
675
End Page
680
DOI
10.1111/j.1365-2982.2007.00945.x

The status of radical proctectomy and sphincter-sparing surgery in the United States - Invited commentary

Authors
Ludwig, KA; Mantyh, CR
MLA Citation
Ludwig, KA, and Mantyh, CR. "The status of radical proctectomy and sphincter-sparing surgery in the United States - Invited commentary." DISEASES OF THE COLON & RECTUM 50.8 (August 2007): 1126-1127.
Source
wos-lite
Published In
Diseases of the Colon and Rectum
Volume
50
Issue
8
Publish Date
2007
Start Page
1126
End Page
1127

Luminally released serotonin stimulates colonic motility and accelerates colonic transit in rats.

Enterochromaffin (EC) cells of the epithelial cells release 5-HT into the lumen, as well as basolateral border. However, the physiological role of released 5-HT into the lumen is poorly understood. Concentrations of 5-HT in the colonic mucosa, colonic lumen, and feces were measured by HPLC in rats. To investigate whether intraluminal 5-HT accelerates colonic transit, 5-HT and (51)Cr were administered into the lumen of the proximal colon, and colonic transit was measured. To investigate whether 5-HT is released into the lumen, we used an ex vivo model of isolated vascularly and luminally perfused rat proximal colon. To investigate whether luminal 5-HT is involved in regulating stress-induced colonic motility, the distal colonic motility was recorded under the stress loading, and a 5-HT(3) receptor antagonist (ondansetron, 10(-6) M, 0.5 ml) was administered intraluminally of the distal colon. Tissue content of 5-HT in the proximal colon (15.2 +/- 4.3 ng/mg wet tissue) was significantly higher than that in the distal colon (3.3 +/- 0.7 ng/mg wet tissue), while fecal content and luminal concentration of 5-HT was almost the same between the proximal and distal colon. Luminal administration of 5-HT (10(-6)-10(-5) M) significantly accelerated colonic transit. Elevation of intraluminal pressure by 10 cmH(2)O significantly increased the luminal concentration of 5-HT but not the vascular concentration of 5-HT. Stress-induced stimulation of the distal colonic motility was significantly attenuated by the luminal administration of ondansetron. These results suggest that luminally released 5-HT from EC cells plays an important role in regulating colonic motility in rats.

Authors
Tsukamoto, K; Ariga, H; Mantyh, C; Pappas, TN; Yanagi, H; Yamamura, T; Takahashi, T
MLA Citation
Tsukamoto, K, Ariga, H, Mantyh, C, Pappas, TN, Yanagi, H, Yamamura, T, and Takahashi, T. "Luminally released serotonin stimulates colonic motility and accelerates colonic transit in rats." Am J Physiol Regul Integr Comp Physiol 293.1 (July 2007): R64-R69.
PMID
17442783
Source
pubmed
Published In
American journal of physiology. Regulatory, integrative and comparative physiology
Volume
293
Issue
1
Publish Date
2007
Start Page
R64
End Page
R69
DOI
10.1152/ajpregu.00856.2006

Bevacizumab, oxaliplatin, and capecitabine with radiation therapy in rectal cancer: Phase I trial results.

PURPOSE: The overexpression of vascular endothelial growth factor (VEGF) is associated with poor outcomes in colorectal cancer patients. Bevacizumab, a VEGF inhibitor, enhances the effects of chemotherapy and radiation therapy on tumor cytotoxicity in preclinical models, including colorectal cancer. A Phase I trial was undertaken to evaluate the combination of bevacizumab, capecitabine, oxaliplatin, and radiation therapy in patients with rectal cancer. METHODS AND MATERIALS: Patients with pathologically confirmed adenocarcinoma of the rectum were eligible. Pretreatment staging included computerized tomography, endoscopic ultrasound, and surgical evaluation. Patients received 50.4 Gy of external beam radiation therapy (EBRT) to the tumor in 28 fractions. Capecitabine, oxaliplatin, and bevacizumab were administered concurrently with radiation therapy. After EBRT completion, patients were restaged and evaluated for surgery. Primary endpoints included the determination of dose-limiting toxicity and a recommended Phase II dose, non dose-limiting toxicity, and preliminary radiographic and pathologic response rates. RESULTS: Eleven patients were enrolled. All were evaluable for toxicity and efficacy. Dose level 2 was associated with unacceptable toxicity (primarily diarrhea). Dose level 1 had an acceptable toxicity profile. The recommended Phase II dose in our study was bevacizumab 15 mg/kg Day 1 + 10 mg/kg Days 8 and 22, oxaliplatin 50 mg/m2 weekly, and capecitabine 625 mg/m2 bid during radiation days. Six patients had clinical responses. Two patients had a pathologic complete response, and 3 had microscopic disease only. One patient experienced a postoperative abscess, one a syncopal episode during adjuvant chemotherapy, and one a subclinical myocardial infarction during adjuvant chemotherapy. CONCLUSIONS: The combination of bevacizumab, capecitabine, oxaliplatin, and radiation therapy in rectal cancer was tolerable, with encouraging response rates. Further investigation with this regimen is being pursued in a Phase II setting.

Authors
Czito, BG; Bendell, JC; Willett, CG; Morse, MA; Blobe, GC; Tyler, DS; Thomas, J; Ludwig, KA; Mantyh, CR; Ashton, J; Yu, D; Hurwitz, HI
MLA Citation
Czito, BG, Bendell, JC, Willett, CG, Morse, MA, Blobe, GC, Tyler, DS, Thomas, J, Ludwig, KA, Mantyh, CR, Ashton, J, Yu, D, and Hurwitz, HI. "Bevacizumab, oxaliplatin, and capecitabine with radiation therapy in rectal cancer: Phase I trial results." Int J Radiat Oncol Biol Phys 68.2 (June 1, 2007): 472-478.
PMID
17498568
Source
pubmed
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
68
Issue
2
Publish Date
2007
Start Page
472
End Page
478
DOI
10.1016/j.ijrobp.2007.02.001

Restraint stress stimulates colonic motility via central corticotropin-releasing factor and peripheral 5-HT3 receptors in conscious rats.

Although restraint stress accelerates colonic transit via a central corticotropin-releasing factor (CRF), the precise mechanism still remains unclear. We tested the hypothesis that restraint stress and central CRF stimulate colonic motility and transit via a vagal pathway and 5-HT(3) receptors of the proximal colon in rats. (51)Cr was injected via the catheter positioned in the proximal colon to measure colonic transit. The rats were subjected to a restraint stress for 90 min or received intracisternal injection of CRF. Ninety minutes after the administration of (51)Cr, the entire colon was removed, and the geometric center (GC) was calculated. Four force transducers were sutured on the proximal, mid, and distal colon to record colonic motility. Restraint stress accelerated colonic transit (GC of 6.7 +/- 0.4, n=6) compared with nonrestraint controls (GC of 5.1 +/- 0.2, n=6). Intracisternal injection of CRF (1.0 microg) also accelerated colonic transit (GC of 7.0 +/- 0.2, n=6) compared with saline-injected group (GC of 4.6 +/- 0.5, n=6). Restraint stress-induced acceleration of colonic transit was reduced by perivagal capsaicin treatment. Intracisternal injection of CRF antagonists (10 microg astressin) abolished restraint stress-induced acceleration of colonic transit. Stimulated colonic transit and motility induced by restraint stress and CRF were significantly reduced by the intraluminal administration of 5-HT(3) antagonist ondansetron (5 x 10(-6) M; 1 ml) into the proximal colon. Restraint stress and intracisternal injection of CRF significantly increased the luminal content of 5-HT of the proximal colon. It is suggested that restraint stress stimulates colonic motility via central CRF and peripheral 5-HT(3) receptors in conscious rats.

Authors
Nakade, Y; Fukuda, H; Iwa, M; Tsukamoto, K; Yanagi, H; Yamamura, T; Mantyh, C; Pappas, TN; Takahashi, T
MLA Citation
Nakade, Y, Fukuda, H, Iwa, M, Tsukamoto, K, Yanagi, H, Yamamura, T, Mantyh, C, Pappas, TN, and Takahashi, T. "Restraint stress stimulates colonic motility via central corticotropin-releasing factor and peripheral 5-HT3 receptors in conscious rats." Am J Physiol Gastrointest Liver Physiol 292.4 (April 2007): G1037-G1044.
PMID
17158256
Source
pubmed
Published In
American journal of physiology. Gastrointestinal and liver physiology
Volume
292
Issue
4
Publish Date
2007
Start Page
G1037
End Page
G1044
DOI
10.1152/ajpgi.00419.2006

Fecal pellet output does not always correlate with colonic transit in response to restraint stress and corticotropin-releasing factor in rats.

BACKGROUND: Fecal pellet output has been assessed as a colonic motor activity because of its simplicity. However, it remains unclear whether an acceleration of colonic transit correlates well with an increase in fecal pellet output. We examined the causal relationship between colonic transit and fecal pellet output stimulated by the central application of corticotropin-releasing factor (CRF) and restraint stress. METHODS: Immediately after intracisternal injection of CRF, (51)Cr was injected via a catheter positioned in the proximal colon. Ninety minutes after (51)Cr injection, the total number of excreted feces was counted, and then the rats were killed. The radioactivity of each colonic segment was evaluated, and the geometric center (GC) of the distribution of (51)Cr was calculated. For the restraint stress study, after administration of (51)Cr into the proximal colon, rats were submitted to wrapping restraint stress for 90 min. Then they were killed, and GC was calculated. RESULTS: Both restraint stress and CRF significantly accelerated colonic transit. There was a positive correlation observed between fecal pellet output and GC of colonic transit in response to restraint stress, but not CRF, when the number of excreted feces was more than three. In contrast, there was no significant correlation observed between the two in stress and CRF when the number of excreted feces was less than two. CONCLUSIONS: The acceleration of colonic transit in response to restraint stress and central administration of CRF does not always correlate with an increase in fecal pellet output.

Authors
Nakade, Y; Mantyh, C; Pappas, TN; Takahashi, T
MLA Citation
Nakade, Y, Mantyh, C, Pappas, TN, and Takahashi, T. "Fecal pellet output does not always correlate with colonic transit in response to restraint stress and corticotropin-releasing factor in rats." J Gastroenterol 42.4 (April 2007): 279-282.
PMID
17464456
Source
pubmed
Published In
Journal of Gastroenterology
Volume
42
Issue
4
Publish Date
2007
Start Page
279
End Page
282
DOI
10.1007/s00535-006-1947-2

Ghrelin administration causes early manifestation of postprandial antro-pyloric coordinations, resulting in rapid gastric emptying in rats

Authors
Ariga, H; Nakade, Y; Chen, C; Mantyh, CR; Pappas, TN; Takahashi, T
MLA Citation
Ariga, H, Nakade, Y, Chen, C, Mantyh, CR, Pappas, TN, and Takahashi, T. "Ghrelin administration causes early manifestation of postprandial antro-pyloric coordinations, resulting in rapid gastric emptying in rats." April 2007.
Source
wos-lite
Published In
Gastroenterology
Volume
132
Issue
4
Publish Date
2007
Start Page
A720
End Page
A720

Luminally released 5-HT from EC cells plays an important role to regulate colonic motility in rats

Authors
Tsukamoto, K; Mochiki, E; Ariga, H; Chen, C; Mantyh, CR; Pappas, TN; Takahashi, T
MLA Citation
Tsukamoto, K, Mochiki, E, Ariga, H, Chen, C, Mantyh, CR, Pappas, TN, and Takahashi, T. "Luminally released 5-HT from EC cells plays an important role to regulate colonic motility in rats." April 2007.
Source
wos-lite
Published In
Gastroenterology
Volume
132
Issue
4
Publish Date
2007
Start Page
A715
End Page
A715

Site-specific effects of electroacupuncturc (EA) on gastric motility in conscious rats; Stimulatory effect of EA at ST-36 is mediated via vagal pathways, while inhibitory effect of EA at ST-25 is mediated via sympathetic pathways

Authors
Imai, K; Chen, C; Mantyh, CR; Pappas, TN; Takahashi, T
MLA Citation
Imai, K, Chen, C, Mantyh, CR, Pappas, TN, and Takahashi, T. "Site-specific effects of electroacupuncturc (EA) on gastric motility in conscious rats; Stimulatory effect of EA at ST-36 is mediated via vagal pathways, while inhibitory effect of EA at ST-25 is mediated via sympathetic pathways." April 2007.
Source
wos-lite
Published In
Gastroenterology
Volume
132
Issue
4
Publish Date
2007
Start Page
A719
End Page
A719

The mechanism of accelerated gastric emptying in the early stage of diabetes: Endogenous ghrelin plays an important role in enhanced manifestation of Antro-PYLORIC coordination in STZ-Induced diabetic rats. Coordination in STZ-Induced diabetic rats

Authors
Ariga, H; Chen, C; Mantyh, CR; Pappas, TN; Takahashi, T
MLA Citation
Ariga, H, Chen, C, Mantyh, CR, Pappas, TN, and Takahashi, T. "The mechanism of accelerated gastric emptying in the early stage of diabetes: Endogenous ghrelin plays an important role in enhanced manifestation of Antro-PYLORIC coordination in STZ-Induced diabetic rats. Coordination in STZ-Induced diabetic rats." April 2007.
Source
wos-lite
Published In
Gastroenterology
Volume
132
Issue
4
Publish Date
2007
Start Page
A719
End Page
A719

Invited commentary [1]

Authors
Ludwig, KA; Mantyh, CR
MLA Citation
Ludwig, KA, and Mantyh, CR. "Invited commentary [1]." Diseases of the Colon and Rectum 50.8 (2007): 1126-1127.
Source
scival
Published In
Diseases of the Colon and Rectum
Volume
50
Issue
8
Publish Date
2007
Start Page
1126
End Page
1127
DOI
10.1007/s10350-007-0250-5

Incidence and patterns of recurrence after resection for cure of colonic cancer in a well-defined population: Commentary

Authors
Mantyh, CR
MLA Citation
Mantyh, CR. "Incidence and patterns of recurrence after resection for cure of colonic cancer in a well-defined population: Commentary." Diseases of the Colon and Rectum 50.1 (2007): 127-128.
Source
scival
Published In
Diseases of the Colon and Rectum
Volume
50
Issue
1
Publish Date
2007
Start Page
127
End Page
128
DOI
10.1007/s10350-005-0243-1

Quality measures for the use of adjuvant chemotherapy and radiation therapy in patients with colorectal cancer: a systematic review.

BACKGROUND: Chemotherapy (CT) and radiation therapy (RT) are essential components of adjuvant (preoperative or postoperative) therapy for many patients with colorectal cancer (CRC); however, quality measures (QMs) of these critical aspects of CRC treatment have not been characterized well. Therefore, the authors conducted a systematic review of the literature to determine the available QMs for adjuvant CT and RT in patients with CRC and rated their usefulness for assessing the delivery of quality care. METHODS: The MEDLINE and Cochrane data bases were searched for all publications that contained potential/actual QMs pertaining to adjuvant therapy for CRC. Identified QMs were rated by using criteria developed by the National Quality Forum. RESULTS: Thirty-two articles met the established inclusion/exclusion criteria. Those 32 articles contained 12 potential or actual QMs, 6 of which had major flaws that limited their applicability. The most useful QMs identified were 1) the percentage of patients with AJCC Stage III colon cancer who received postoperative CT and 2) the percentage of patients with Stage II or III rectal cancer who received chemoradiotherapy. CONCLUSIONS: To the authors' knowledge, very few QMs pertaining to adjuvant CT or RT for CRC have been published to date, and only half of those measures were rated as useful, acceptable, and valid in the current literature review. Future research should focus on refining existing QMs and on developing new QMs that target important leverage points with respect to the provision of adjuvant therapy for patients with CRC.

Authors
Prosnitz, RG; Patwardhan, MB; Samsa, GP; Mantyh, CR; Fisher, DA; McCrory, DC; Cline, KE; Gray, RN; Morse, MA
MLA Citation
Prosnitz, RG, Patwardhan, MB, Samsa, GP, Mantyh, CR, Fisher, DA, McCrory, DC, Cline, KE, Gray, RN, and Morse, MA. "Quality measures for the use of adjuvant chemotherapy and radiation therapy in patients with colorectal cancer: a systematic review." Cancer 107.10 (November 15, 2006): 2352-2360. (Review)
PMID
17039499
Source
pubmed
Published In
Cancer
Volume
107
Issue
10
Publish Date
2006
Start Page
2352
End Page
2360
DOI
10.1002/cncr.22278

The selective mu opioid receptor antagonist, alvimopan, improves delayed GI transit of postoperative ileus in rats.

Postoperative ileus (POI) is often exacerbated by opioid analgesic use during and following surgery, since mu opioid receptor activation results in a further delay of gastrointestinal (GI) transit. The effects of alvimopan, a novel, selective, and peripherally acting mu opioid receptor antagonist, and the reference compound methylnaltrexone, upon POI were investigated in rats. Under isoflurane anesthesia, POI was induced by laparotomy with intestinal manipulation. Immediately after the surgery, the rats received (51)Cr by gavage. Three hours after the surgery, the rats were sacrificed and GI transit was estimated using the geometric center (GC) of (51)Cr. Alvimopan (0.1-3 mg/kg) or methylnaltrexone (100 mg/kg) were administered by gavage either before or after the surgery, with or without morphine administration (1 mg/kg). GI transit was delayed by intestinal manipulation (GC = 2.92 +/- 0.17). Alvimopan (1 and 3 mg/kg) significantly reversed this delayed GI transit when administered 45 min prior to surgery. However, the effects of alvimopan were less pronounced when administered following surgery. Morphine administration further delayed GI transit induced by intestinal manipulation (GC = 1.97 +/- 0.11). Under these conditions, alvimopan (1 and 3 mg/kg) also significantly improved delayed GI transit when administered before surgery. Methylnaltrexone was inactive under all experimental conditions. These data suggest that mu opioid receptors play a role in the pathogenesis of POI, and that the clinical benefit reported to be afforded by alvimopan may be in part mediated via inhibition of an endogenous opioid release as well as blockade of the unwanted GI actions of analgesic agents.

Authors
Fukuda, H; Suenaga, K; Tsuchida, D; Mantyh, CR; Pappas, TN; Hicks, GA; Dehaven-Hudkins, DL; Takahashi, T
MLA Citation
Fukuda, H, Suenaga, K, Tsuchida, D, Mantyh, CR, Pappas, TN, Hicks, GA, Dehaven-Hudkins, DL, and Takahashi, T. "The selective mu opioid receptor antagonist, alvimopan, improves delayed GI transit of postoperative ileus in rats." Brain Res 1102.1 (August 2, 2006): 63-70.
PMID
16797494
Source
pubmed
Published In
Brain Research
Volume
1102
Issue
1
Publish Date
2006
Start Page
63
End Page
70
DOI
10.1016/j.brainres.2006.02.092

Quality measures for the diagnosis and management of colorectal cancer.

16031 Background: The huge burden of illness from colorectal cancer (CRC) can be reduced by improving the quality of care for CRC patients. Identifying appropriate quality measures that can assess the processes of care is the first step in this process. Therefore we conducted a comprehensive literature search to identify process measures available in the United States to assess the quality of care for diagnosing and managing patients with CRC and the extent to which they were field-ready.We conducted a standard literature search using MEDLINE and the Cochrane Database; also explored gray literature, and identified 3771 abstracts. By sequential exclusion, 74 of them were finally included. We included quality measures from traditional QI literature, and supplemented them with those included in studies where these measures were used as part of their research agenda. All measures were abstracted into evidence tables and evaluated using a set of standard criteria regarding their importance, usability, and scientific acceptability. In order to assess the extent to which they were field-ready, we devised a summary rating scale for each quality measure using three criteria: importance and usability, scientific acceptability, and extent of testing.Overall, the coverage of general process measures in CRC is extensive. Process measures are available for diagnostic imaging, staging, surgical therapy, adjuvant chemotherapy, adjuvant radiation therapy, and colonoscopic surveillance. The highest rated measures were those related to chemotherapy (abstract submitted by Morse et al) and pathology reporting. There were no process measures for assessing the quality of: polyp removal, surgical management of stage IV rectal cancer, hepatic metastasis, chemotherapy for stage II colon cancer, stage IV rectal cancer, radiation for stage IV rectal cancer, and notes for endoscopy, surgery, chemotherapy and radiology - all because of lack of guidelines.Our evidence report suggests that we need to actively pursue the task of developing scientifically accurate quality measures for leverage points in the diagnosis and management of CRC; so we can evaluate the quality of care delivered by providers and initiate quality improvement activities, with the aim of providing better patient care. No significant financial relationships to disclose.

Authors
Patwardhan, MB; Samsa, GP; Michael, MA; Prosnitz, RG; Fisher, DA; Mantyh, CR; McCrory, DC
MLA Citation
Patwardhan, MB, Samsa, GP, Michael, MA, Prosnitz, RG, Fisher, DA, Mantyh, CR, and McCrory, DC. "Quality measures for the diagnosis and management of colorectal cancer." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 24.18_suppl (June 2006): 16031-.
PMID
27954983
Source
epmc
Published In
Journal of Clinical Oncology
Volume
24
Issue
18_suppl
Publish Date
2006
Start Page
16031

Peripherally administered CRF stimulates colonic motility via central CRF receptors and vagal pathways in conscious rats.

Corticotropin releasing factor (CRF) is one of the most important factors in the mechanism of stress-induced stimulation of colonic motility. However, it is controversial whether stress-induced stimulation of colonic motility is mediated via central or peripheral CRF receptors. We investigated the hypothesis that peripherally injected CRF accelerates colonic motility through the central CRF receptor, but not the peripheral CRF receptor. A strain gauge transducer was sutured on the serosal surface of the proximal colon. Colonic motility was monitored before and after the peripheral injection of CRF. An in vitro muscle strip study was also performed to investigate the peripheral effects of CRF. Subcutaneous injection of CRF (30-100 microg/kg) stimulated colonic motility in a dose-dependent manner. The stimulatory effect of peripherally administered CRF on colonic motility was abolished by truncal vagotomy, hexamethonium, atropine, and intracisternal injection of astressin (a CRF receptor antagonist). No responses to CRF (10(-9) -10(-7) M) of the muscle strips of the proximal colon were observed. These results suggest that the stimulatory effect of colonic motility in response to peripheral administration of CRF is mediated by the vagus nerve, nicotinic receptors, muscarinic receptors, and CRF receptors of the brain stem. It is concluded that peripherally administered CRF reaches the area postrema and activates the dorsal nucleus of vagi via central CRF receptors, resulting in stimulation of the vagal efferent and cholinergic transmission of the proximal colon.

Authors
Tsukamoto, K; Nakade, Y; Mantyh, C; Ludwig, K; Pappas, TN; Takahashi, T
MLA Citation
Tsukamoto, K, Nakade, Y, Mantyh, C, Ludwig, K, Pappas, TN, and Takahashi, T. "Peripherally administered CRF stimulates colonic motility via central CRF receptors and vagal pathways in conscious rats." Am J Physiol Regul Integr Comp Physiol 290.6 (June 2006): R1537-R1541.
PMID
16284082
Source
pubmed
Published In
American journal of physiology. Regulatory, integrative and comparative physiology
Volume
290
Issue
6
Publish Date
2006
Start Page
R1537
End Page
R1541
DOI
10.1152/ajpregu.00713.2005

Cancer care quality measures: diagnosis and treatment of colorectal cancer.

OBJECTIVES: To identify measures that are currently available to assess the quality of care provided to patients with colorectal cancer (CRC), and to assess the extent to which these measures have been developed and tested. DATA SOURCES: Published and unpublished measures identified through a computerized search of English-language citations in MEDLINE (1966-January 2005), the Cochrane Database of Systematic Reviews, and the National Guideline Clearinghouse; through review of reference lists contained in seed articles, all included articles, and relevant review articles; and through searches of the grey literature (institutional or government reports, professional society documents, research papers, and other literature, in print or electronic format, not controlled by commercial publishing interests). Sources for grey literature included professional organization websites and the Internet. REVIEW METHODS: Measures were selected by reviewers according to standardized criteria relating to each question, and were then rated according to their importance and usability, scientific acceptability, and extent of testing; each domain was rated from 1 (poor) to 5 (ideal). RESULTS: We identified a number of well-developed and well-tested CRC-related quality-of-care measures, both general process-of-care measures (on a broader scale) and technical measures (pertaining to specific details of a procedure). At least some process measures are available for diagnostic imaging, staging, surgical therapy, adjuvant chemotherapy, adjuvant radiation therapy, and colonoscopic surveillance. Various technical measures were identified for quality of colonoscopy (e.g., cecal intubation rate, complications) and staging (adequate lymph node retrieval and evaluation). These technical measures were guideline-based and well developed, but less well tested, and the linkage between them and patient outcomes, although intuitive, was not always explicitly provided. For some elements of the care pathway, such as operative reports and chemotherapy reports, no technical measures were found. CONCLUSIONS: Some general process measures have a stronger evidence base than others. Those based on guidelines have the strongest evidence base; those derived from basic first principles supported by some research findings are relatively weaker, but are often sufficient for the task at hand. A consistent source of tension is the distinction between the clinically derived fine-tuning of the definition of a quality measure and the limitations of available data sources (which often do not contain sufficient information to act on such distinctions). Although some excellent technical measures were found, the overall development of technical measures seems less advanced than that of the general process measures.

Authors
Patwardhan, MB; Samsa, GP; McCrory, DC; Fisher, DA; Mantyh, CR; Morse, MA; Prosnitz, RG; Cline, KE; Gray, RN
MLA Citation
Patwardhan, MB, Samsa, GP, McCrory, DC, Fisher, DA, Mantyh, CR, Morse, MA, Prosnitz, RG, Cline, KE, and Gray, RN. "Cancer care quality measures: diagnosis and treatment of colorectal cancer." Evid Rep Technol Assess (Full Rep) 138 (May 2006): 1-116. (Review)
PMID
17764215
Source
pubmed
Published In
Evidence report/technology assessment
Issue
138
Publish Date
2006
Start Page
1
End Page
116

The herbal medicine, Dai-Kenchu-to, accelerates delayed gastrointestinal transit after the operation in rats.

BACKGROUND: Post-operative ileus (POI) is a transient bowel dysmotility after operation. We have previously shown that laparotomy alone significantly delayed gastrointestinal (GI) transit, compared to anesthesia alone. The GI transit was further delayed after laparotomy plus intestinal manipulation. Dai-Kenchu-to (DKT), an herbal medicine, has been used for treating adhesive bowel obstruction in Japan. We studied whether DKT improves delayed GI transit after the operation, with or without morphine administration in rats. MATERIALS AND METHODS: Under isoflurane anesthesia, POI was induced by laparotomy with intestinal manipulation. Immediately after the operation, the rats received 51Cr by gavage. Three hours after the operation, the rats were sacrificed and GI transit was estimated by calculating the geometric center (GC). DKT (120, 360, and 1,200 mg/kg) were administered by gavage after the operation, with or without morphine administration (1 mg/kg s.c.). A muscarinic receptor antagonist (atropine; 50 mug/kg), a 5HT3 receptor antagonist (ondansetron; 1 mg/kg) and a 5HT4 receptor antagonist (GR113,808; 3 mg/kg) were administered before the operation. Truncal vagotomy was performed preceding the operation. RESULTS: Laparotomy with intestinal manipulation produced a significant delay in GI transit (GC = 2.93 +/- 0.16), compared to that of anesthesia alone (9.51 +/- 0.45). DKT at the dose of 360 mg/kg (GC = 3.77 +/- 0.10, P < 0.01) and 1,200 mg/kg (GC = 3.77 +/- 0.20, P < 0.01) significantly accelerated delayed GI transit induced by operation. Ondansetron, GR113,808, atropine, and truncal vagotomy abolished the stimulatory effect of DKT (360 mg/kg). When morphine was administered, GI transit was further reduced (GC = 1.97 +/- 0.10). DKT at the dose of 360 mg/kg (GC = 2.81 +/- 0.22, P < 0.05) and 1,200 mg/kg (GC = 2.87 +/- 0.23, P < 0.05) significantly improved delayed GI transit in morphine treated rats. CONCLUSIONS: DKT accelerates delayed GI transit induced by intestinal manipulation with and without concomitant morphine administration. DKT treatment may be useful for the patients with POI.

Authors
Fukuda, H; Chen, C; Mantyh, C; Ludwig, K; Pappas, TN; Takahashi, T
MLA Citation
Fukuda, H, Chen, C, Mantyh, C, Ludwig, K, Pappas, TN, and Takahashi, T. "The herbal medicine, Dai-Kenchu-to, accelerates delayed gastrointestinal transit after the operation in rats." J Surg Res 131.2 (April 2006): 290-295.
PMID
16259999
Source
pubmed
Published In
Journal of Surgical Research
Volume
131
Issue
2
Publish Date
2006
Start Page
290
End Page
295
DOI
10.1016/j.jss.2005.09.018

Central glucagon like peptide-1 accelerates colonic transit via a central CRF and peripheral parasympathetic pathway in conscious rats

Authors
Nakade, Y; Tsukamoto, K; Masere, C; Ludwig, K; Mantyh, CR; Pappas, TN; Takahashi, T
MLA Citation
Nakade, Y, Tsukamoto, K, Masere, C, Ludwig, K, Mantyh, CR, Pappas, TN, and Takahashi, T. "Central glucagon like peptide-1 accelerates colonic transit via a central CRF and peripheral parasympathetic pathway in conscious rats." April 2006.
Source
wos-lite
Published In
Gastroenterology
Volume
130
Issue
4
Publish Date
2006
Start Page
A90
End Page
A90

Quality measures for colorectal cancer diagnosis: A systematic review

Authors
Fisher, DA; Mantyh, CR; Morse, MA; Prosnitz, RG; Samsa, GR; Patwardhan, MB
MLA Citation
Fisher, DA, Mantyh, CR, Morse, MA, Prosnitz, RG, Samsa, GR, and Patwardhan, MB. "Quality measures for colorectal cancer diagnosis: A systematic review." April 2006.
Source
wos-lite
Published In
Gastroenterology
Volume
130
Issue
4
Publish Date
2006
Start Page
A616
End Page
A616

Increased toxicity with gefitinib, capecitabine, and radiation therapy in pancreatic and rectal cancer: phase I trial results.

PURPOSE: Overexpression of epidermal growth factor receptor (EGFR) has been associated with aggressive tumor phenotypes, chemotherapy, and radiation resistance, as well as poor survival in preclinical and clinical models. The EGFR inhibitor gefitinib potentiates chemotherapy and radiation tumor cytotoxicity in preclinical models, including pancreatic and colorectal cancer. We initiated two phase I trials assessing the combination of gefitinib, capecitabine, and radiation in patients with localized pancreatic and rectal cancer. PATIENTS AND METHODS: Patients with pathologically confirmed adenocarcinoma of the pancreas and rectum were eligible. Pretreatment staging included computed tomography, endoscopic ultrasound, and surgical evaluation. Patients received 50.4 Gy of external-beam radiation therapy to the tumor in 28 fractions. Capecitabine and gefitinib were administered throughout the radiation course. Following completion, patients were restaged and considered for resection. Primary end points included determination of dose-limiting toxicity (DLT) and a phase II dose; secondary end points included determination of non-DLTs and preliminary radiographic and pathologic response rates. RESULTS: Ten patients were entered in the pancreatic study and six in the rectal study. DLT was seen in six of 10 patients in the pancreatic study and two of six patients in the rectal study. The primary DLT in both studies was diarrhea. Two patients developed arterial thrombi. CONCLUSION: The combination of gefitinib, capecitabine, and radiation in pancreatic and rectal cancer patients resulted in significant toxicity. A recommended phase II dose was not determined in either of our studies. Further investigation with this combination should be approached with caution.

Authors
Czito, BG; Willett, CG; Bendell, JC; Morse, MA; Tyler, DS; Fernando, NH; Mantyh, CR; Blobe, GC; Honeycutt, W; Yu, D; Clary, BM; Pappas, TN; Ludwig, KA; Hurwitz, HI
MLA Citation
Czito, BG, Willett, CG, Bendell, JC, Morse, MA, Tyler, DS, Fernando, NH, Mantyh, CR, Blobe, GC, Honeycutt, W, Yu, D, Clary, BM, Pappas, TN, Ludwig, KA, and Hurwitz, HI. "Increased toxicity with gefitinib, capecitabine, and radiation therapy in pancreatic and rectal cancer: phase I trial results." J Clin Oncol 24.4 (February 1, 2006): 656-662.
PMID
16446337
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
24
Issue
4
Publish Date
2006
Start Page
656
End Page
662
DOI
10.1200/JCO.2005.04.1749

Comparative analysis of vagotomy and drainage versus vagotomy and resection procedures for bleeding peptic ulcer disease: results of 907 patients from the Department of Veterans Affairs National Surgical Quality Improvement Program database.

BACKGROUND: The purpose of this study was to determine postoperative outcomes and risk factors for morbidity and mortality in patients requiring surgery for bleeding peptic ulcer disease (PUD). Vagotomy and drainage procedures are technically simpler but are usually associated with higher ulcer recurrence rates. In contrast, vagotomy and resection approaches offer lower ulcer recurrences but represent much more challenging operations and are associated with considerable morbidity and mortality. STUDY DESIGN: Data collected through the Department of Veterans Affairs National Surgical Quality Improvement Program database from 1991 to 2001 were submitted for stepwise logistic regression analysis for prediction of 30-day postoperative morbidity and mortality, rebleeding, and postoperative length of stay. The study population included all patients operated on for bleeding PUD within an 11-year period. RESULTS: The 30-day morbidity, mortality, and rebleeding rates were comparable between surgical groups. Age, American Society of Anesthesiologists class, presence of ascites, coma, diabetes, functional status, hemiplegia, and history of steroid use were predictors of postoperative death. Risk factors for rebleeding included dependent functional status, history of congestive heart failure, smoking, steroid use, and preoperative transfusions. Having a resective procedure, American Society of Anesthesiologists class, hemiplegia, history of COPD, and requiring ventilator-assisted respirations before surgery were positively associated with increased length of hospital stay. CONCLUSIONS: No differences were observed in 30-day mortality, morbidity, or rebleeding rates between surgical groups. Having a resective procedure was a predictor of prolonged postoperative stay. Dependent status and chronic use of steroids were predictors of both rebleeding and postoperative mortality.

Authors
de la Fuente, SG; Khuri, SF; Schifftner, T; Henderson, WG; Mantyh, CR; Pappas, TN
MLA Citation
de la Fuente, SG, Khuri, SF, Schifftner, T, Henderson, WG, Mantyh, CR, and Pappas, TN. "Comparative analysis of vagotomy and drainage versus vagotomy and resection procedures for bleeding peptic ulcer disease: results of 907 patients from the Department of Veterans Affairs National Surgical Quality Improvement Program database." J Am Coll Surg 202.1 (January 2006): 78-86.
PMID
16377500
Source
pubmed
Published In
Journal of The American College of Surgeons
Volume
202
Issue
1
Publish Date
2006
Start Page
78
End Page
86
DOI
10.1016/j.jamcollsurg.2005.09.001

Attenuation of acid induced oesophagitis in VR-1 deficient mice.

BACKGROUND AND AIMS: Activation of the vanilloid receptor subtype 1 (VR-1) results in release of proinflammatory peptides which initiate an inflammatory cascade known as neurogenic inflammation. We investigated its role in an acute model of surgically induced oesophagitis. METHODS: Oesophagitis was induced by pyloric ligation in wild-type and VR-1 deficient mice. A subset of animals were administered the VR-1 antagonist capsazepine, famotidine, or omeprazole one hour before surgery. Five hours after surgery, myeloperoxidase activity (MPO), histological damage scores, intragastric pH, and immunocytochemical analysis of substance P (SP) receptor endocytosis were determined. RESULTS: Oesophagitis induced knockout mice exhibited significantly lower levels of MPO activity, histological damage scores, and SP receptor endocytosis than wild-type mice. Inflammatory parameters were significantly reduced by acid inhibition and capsazepine in wild-type mice. CONCLUSIONS: We conclude that acute acid induced oesophagitis is reduced in animals lacking VR-1. This suggests that acid induced oesophagitis may act through VR-1 and that inhibition of the receptor may reduce inflammation.

Authors
Fujino, K; de la Fuente, SG; Takami, Y; Takahashi, T; Mantyh, CR
MLA Citation
Fujino, K, de la Fuente, SG, Takami, Y, Takahashi, T, and Mantyh, CR. "Attenuation of acid induced oesophagitis in VR-1 deficient mice." Gut 55.1 (January 2006): 34-40.
PMID
16091555
Source
pubmed
Published In
Gut
Volume
55
Issue
1
Publish Date
2006
Start Page
34
End Page
40
DOI
10.1136/gut.2005.066795

Population-based study of prognostic factors in stage II colonic cancer: Commentary

Authors
Mantyh, CR
MLA Citation
Mantyh, CR. "Population-based study of prognostic factors in stage II colonic cancer: Commentary." Diseases of the Colon and Rectum 49.10 (2006): 1656--.
Source
scival
Published In
Diseases of the Colon and Rectum
Volume
49
Issue
10
Publish Date
2006
Start Page
1656-
DOI
10.1007/s10350-006-0241-y

Meta-analysis of colonic reserviors versus straight coloanal anastomosis after anterior resection

Authors
Mantyh, CR
MLA Citation
Mantyh, CR. "Meta-analysis of colonic reserviors versus straight coloanal anastomosis after anterior resection." 2006.
Source
scival
Published In
Diseases of the Colon and Rectum
Volume
49
Issue
8
Publish Date
2006
Start Page
1249
End Page
1250
DOI
10.1007/s10350-005-0239-x

Long-term results in patients with T2-3 N0 distal rectal cancer undergoing radiotherapy before transanal endoscopic microsurgery: Editorial comment

Authors
Mantyh, CR
MLA Citation
Mantyh, CR. "Long-term results in patients with T2-3 N0 distal rectal cancer undergoing radiotherapy before transanal endoscopic microsurgery: Editorial comment." Diseases of the Colon and Rectum 49.5 (2006): 699--.
Source
scival
Published In
Diseases of the Colon and Rectum
Volume
49
Issue
5
Publish Date
2006
Start Page
699-
DOI
10.1007/s10350-005-0237-z

Salvage reoperation for complications after ileal pouch-anal anastomosis: Commentary

Authors
Mantyh, C
MLA Citation
Mantyh, C. "Salvage reoperation for complications after ileal pouch-anal anastomosis: Commentary." Diseases of the Colon and Rectum 49.3 (2006): 420-421.
Source
scival
Published In
Diseases of the Colon and Rectum
Volume
49
Issue
3
Publish Date
2006
Start Page
420
End Page
421
DOI
10.1007/s10350-005-0231-5

Coloanal anastomotic integrity after total mesorectal excision is not compromised by preoperative chemoradiation for rectal cancer

Authors
Kalady, MF; Onaitis, MW; Mantyh, CR; Tyler, DS; Ludwig, KA
MLA Citation
Kalady, MF, Onaitis, MW, Mantyh, CR, Tyler, DS, and Ludwig, KA. "Coloanal anastomotic integrity after total mesorectal excision is not compromised by preoperative chemoradiation for rectal cancer." March 2005.
Source
wos-lite
Published In
Diseases of the Colon and Rectum
Volume
48
Issue
3
Publish Date
2005
Start Page
601
End Page
602

Inhibition of sympathetic pathways improves postoperative ileus in the upper and lower gastrointestinal tract

Authors
Takahashi, T; Fukuda, H; Tsuchida, D; Mantyh, CR; Pappas, TN; Ludwig, KA
MLA Citation
Takahashi, T, Fukuda, H, Tsuchida, D, Mantyh, CR, Pappas, TN, and Ludwig, KA. "Inhibition of sympathetic pathways improves postoperative ileus in the upper and lower gastrointestinal tract." March 2005.
Source
wos-lite
Published In
Diseases of the Colon and Rectum
Volume
48
Issue
3
Publish Date
2005
Start Page
606
End Page
607

Routine contrast imaging of low pelvic anastomosis before defunctioning ileostomy closure: Is it necessary?

Authors
Kalady, MF; Mantyh, CR; Ludwig, KA
MLA Citation
Kalady, MF, Mantyh, CR, and Ludwig, KA. "Routine contrast imaging of low pelvic anastomosis before defunctioning ileostomy closure: Is it necessary?." March 2005.
Source
wos-lite
Published In
Diseases of the Colon and Rectum
Volume
48
Issue
3
Publish Date
2005
Start Page
623
End Page
624

Surgical autonomic denervation results in altered colonic motility

Authors
Lee, WY; Takahashi, T; Mantyh, CR; Pappas, TN; Ludwig, KA
MLA Citation
Lee, WY, Takahashi, T, Mantyh, CR, Pappas, TN, and Ludwig, KA. "Surgical autonomic denervation results in altered colonic motility." March 2005.
Source
wos-lite
Published In
Diseases of the Colon and Rectum
Volume
48
Issue
3
Publish Date
2005
Start Page
683
End Page
683

Inhibition of the vanilloid receptor subtype-1 attenuates TNBS-colitis.

Primary sensory neurons are important in regard to the initiation and propagation of intestinal inflammation. The vanilloid receptor subtype-1 (VR-1) is a cation channel located on the sensory nerves that, when stimulated, release proinflammatory peptides. Previous reports have indicated that inhibition of VR-1 with capsazepine (CPZ), a VR-1 antagonist, attenuates dextran sodium sulfate (DSS) colitis in rats. DSS-induced colitis resembles ulcerative colitis with regard to its pathologic features. In this study, we examined the effect of CPZ on trinitrobenzene sulfonic acid (TNBS)-induced colitis, an experimental model of intestinal inflammation that most closely resembles the histologic and microscopic features of Crohn's disease. Colitis was induced by administering a single enema of 100 mg/kg TNBS in 50% ethanol via catheter to lightly anesthetized rats. Subsets of rats were treated with either 1 micromol/kg/ml of CPZ or CPZ-vehicle via enema for 6 days. Seven days after TNBS administration, rats were sacrificed and inflammation was assessed using a validated macroscopic damage score (MDS) and by measuring myeloperoxidase (MPO) activity. In addition, histologic examination was performed. TNBS administration resulted in reproducible chronic erosive lesions extending into the muscularis propria and extensive recruitment of neutrophils in the distal colon. MDS and MPO scores were considerably elevated in the TNBS colons when compared with the TNBS vehicle animals. TNBS rats treated with CPZ enemas exhibited a substantial reduction in MDS and MPO scores and demonstrated dramatically improved pathologic findings. Topical CPZ resulted in considerable attenuation of TNBS-induced colitis. These results support the role of VR-1 and sensory neurons with regard to intestinal inflammation.

Authors
Fujino, K; Takami, Y; de la Fuente, SG; Ludwig, KA; Mantyh, CR
MLA Citation
Fujino, K, Takami, Y, de la Fuente, SG, Ludwig, KA, and Mantyh, CR. "Inhibition of the vanilloid receptor subtype-1 attenuates TNBS-colitis." J Gastrointest Surg 8.7 (November 2004): 842-847.
PMID
15531237
Source
pubmed
Published In
Journal of Gastrointestinal Surgery
Volume
8
Issue
7
Publish Date
2004
Start Page
842
End Page
847
DOI
10.1016/j.gassur.2004.07.011

Magnitude of abdominal incision affects the duration of postoperative ileus in rats.

BACKGROUND: The pathogenesis of reduced postoperative ileus (POI) in laparoscopic gastrointestinal (GI) surgery still remains controversial. The aim of this study was to investigate the effect of surgical incision on postoperative ileus. METHODS: The effects of length, depth, and site of the incision on GI transit were compared using the geometric center of 51Cr in rats. The inhibitory mechanism of abdominal incision on GI transit also was studied. RESULTS: The findings showed that 5 cm of abdominal skin and the 5-cm back muscle incision had no significant effect on GI transit. However, the 5-cm abdominal muscle-fascia incision and a 5-cm laparotomy significantly delayed GI transit. Gastrointestinal transit after a 5-cm laparotomy was significantly delayed, as compared with that of a 1-cm laparotomy regardless whether intestinal manipulation was performed or not. Guanethidine and yohimbine, but not propranolol, significantly improved the impaired GI transit after a 5-cm laparotomy. CONCLUSIONS: The results suggest that the longer and deeper abdominal incision more profoundly inhibits GI transit. The inhibitory effect of abdominal incision is mediated via the activation of the somatosympathetic reflex and alpha-2 adrenoceptors.

Authors
Uemura, K; Tatewaki, M; Harris, MB; Ueno, T; Mantyh, CR; Pappas, TN; Takahashi, T
MLA Citation
Uemura, K, Tatewaki, M, Harris, MB, Ueno, T, Mantyh, CR, Pappas, TN, and Takahashi, T. "Magnitude of abdominal incision affects the duration of postoperative ileus in rats." Surg Endosc 18.4 (April 2004): 606-610.
PMID
14752646
Source
pubmed
Published In
Surgical Endoscopy
Volume
18
Issue
4
Publish Date
2004
Start Page
606
End Page
610
DOI
10.1007/s00464-003-8161-6

Attenuation of acid-induced esophagitis in mice deficient in the vanilloid receptor subtype-1

Authors
Fujino, K; de la Fuente, S; Vigna, SR; Mantyh, CR
MLA Citation
Fujino, K, de la Fuente, S, Vigna, SR, and Mantyh, CR. "Attenuation of acid-induced esophagitis in mice deficient in the vanilloid receptor subtype-1." April 2004.
Source
wos-lite
Published In
Gastroenterology
Volume
126
Issue
4
Publish Date
2004
Start Page
A48
End Page
A48

Intestinal manipulation causes postoperative ileus via an inhibitory sympathetic efferent pathway

Authors
Fukuda, H; Tsuchida, D; Mantyh, CR; Pappas, TN; Takahashi, T
MLA Citation
Fukuda, H, Tsuchida, D, Mantyh, CR, Pappas, TN, and Takahashi, T. "Intestinal manipulation causes postoperative ileus via an inhibitory sympathetic efferent pathway." April 2004.
Source
wos-lite
Published In
Gastroenterology
Volume
126
Issue
4
Publish Date
2004
Start Page
A223
End Page
A223

The selective Mu opioid receptor antagonist, alvimopan, accelerates gastrointestinal transit in a rodent model of postoperative ileus

Authors
Fukuda, H; Suenaga, K; Uemura, K; Tsuchida, D; Mantyh, CR; Papas, TN; Hicks, GA; Takahashi, T
MLA Citation
Fukuda, H, Suenaga, K, Uemura, K, Tsuchida, D, Mantyh, CR, Papas, TN, Hicks, GA, and Takahashi, T. "The selective Mu opioid receptor antagonist, alvimopan, accelerates gastrointestinal transit in a rodent model of postoperative ileus." April 2004.
Source
wos-lite
Published In
Gastroenterology
Volume
126
Issue
4
Publish Date
2004
Start Page
A641
End Page
A641

Inhibition of the vanilloid receptor subtype-1 attenuates TNBS-induced colitis

Authors
Fujino, K; Takami, Y; De La Fuente, S; Ludwig, KA; Vigna, SR; Mantyh, CR
MLA Citation
Fujino, K, Takami, Y, De La Fuente, S, Ludwig, KA, Vigna, SR, and Mantyh, CR. "Inhibition of the vanilloid receptor subtype-1 attenuates TNBS-induced colitis." April 2004.
Source
wos-lite
Published In
Gastroenterology
Volume
126
Issue
4
Publish Date
2004
Start Page
A772
End Page
A772

A Phase I trial of preoperative eniluracil plus 5-fluorouracil and radiation for locally advanced or unresectable adenocarcinoma of the rectum and colon.

PURPOSE: Eniluracil, an effective inactivator of dihydropyrimidine dehydrogenase, allows for oral dosing of 5-fluorouracil (5-FU), which avoids the morbidity of continuous infusion 5-FU. We addressed the safety of oral eniluracil and 5-FU combined with preoperative radiotherapy and determined the recommended Phase II dose and dose-limiting toxicity in patients with locally advanced rectal and colon cancer. METHODS AND MATERIALS: Patients with TNM Stage II or III rectal cancer and residual or recurrent colon cancer received eniluracil (starting at 6.0 mg/m(2) every 12 h) and 5-FU (starting at 0.6 mg/m(2) every 12 h). Eniluracil and 5-FU were given with a 5-week course of preoperative radiotherapy of 4500 cGy, with a possible 540-cGy boost. Surgery was performed approximately 4 weeks after completion of chemoradiotherapy. RESULTS: Twenty-two patients were enrolled; 1 patient was withdrawn owing to noncompliance. Chemotherapy was completed in all patients; radiotherapy was completed in 20 patients. The recommended Phase II dose of eniluracil and 5-FU was 8 mg/m(2) every 12 h and 0.8 mg/m(2) every 12 h, respectively. Diarrhea was the dose-limiting toxicity. Eleven of the 17 patients with primary rectal cancer underwent a sphincter-sparing procedure. One patient had a pathologic complete response. CONCLUSION: Preoperative chemoradiotherapy with oral eniluracil and 5-FU is feasible and well tolerated. Additional investigation is warranted.

Authors
Czito, BG; Hong, TJ; Cohen, DP; Tyler, DS; Lee, CG; Anscher, MS; Ludwig, KA; Seigler, HF; Mantyh, C; Morse, MA; Lockhart, AC; Petros, WP; Honeycutt, W; Spector, NL; Ertel, PJ; Mangum, SG; Hurwitz, HI
MLA Citation
Czito, BG, Hong, TJ, Cohen, DP, Tyler, DS, Lee, CG, Anscher, MS, Ludwig, KA, Seigler, HF, Mantyh, C, Morse, MA, Lockhart, AC, Petros, WP, Honeycutt, W, Spector, NL, Ertel, PJ, Mangum, SG, and Hurwitz, HI. "A Phase I trial of preoperative eniluracil plus 5-fluorouracil and radiation for locally advanced or unresectable adenocarcinoma of the rectum and colon." Int J Radiat Oncol Biol Phys 58.3 (March 1, 2004): 779-785.
PMID
14967434
Source
pubmed
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
58
Issue
3
Publish Date
2004
Start Page
779
End Page
785
DOI
10.1016/S0360-3016(03)01567-0

Ileal pouch-anal anastomosis for ulcerative colitis and familial adenomatous polyposis: historical development and current status.

In summary, the history and development of the proctocolectomy and ileal pouch-anal anastomosis has involved innovative animal and clinical research by several surgical investigators. This evolution followed the classic process of academic surgical progress: a clinical problem is identified; solutions are studied in the laboratory; and these solutions are applied back to the clinical situation with success. Dr. Sabiston's disappointment with clinical results in ulcerative colitis and familial polyposis patients led to laboratory experiments in which a new technique was shown safe in dogs. The further work of his collaborator Dr. Ravitch as well as that of Sir Alan Parks and Dr. Utsunoimya proved small-scale clinical application of the new technique. Finally, large-scale outcomes work by Dr. Fazio at the Cleveland Clinic Foundation and others has allowed further refinements to occur and has highlighted other areas to study. The work of these investigators and other has allowed lack of a permanent ostomy with satisfactory functional results in more than 95% of patients. Continued experience with these procedures has and will lead to further improvements in operative times, morbidity rates, and functional results. Although research in this area will continue, the evolution of this operation has allowed it to become the gold standard for the treatment of ulcerative colitis and familial adenomatous polyposis.

Authors
Onaitis, MW; Mantyh, C
MLA Citation
Onaitis, MW, and Mantyh, C. "Ileal pouch-anal anastomosis for ulcerative colitis and familial adenomatous polyposis: historical development and current status." Ann Surg 238.6 Suppl (December 2003): S42-S48. (Review)
PMID
14703744
Source
pubmed
Published In
Annals of Surgery
Volume
238
Issue
6 Suppl
Publish Date
2003
Start Page
S42
End Page
S48

Elective stoma construction improves outcomes in medically intractable pressure ulcers.

PURPOSE: Perineal pressure ulcers are a common and devastating complication for paralyzed or chronically bedridden patients. Controversy exists on the benefit of fecal diversion for the treatment and prevention of these ulcers. This study compared outcomes in bed-bound patients with pressure ulcers who electively underwent fecal diversion with those who did not. METHODS: A retrospective review was performed on all disabled patients who underwent surgery for medically intractable pressure ulcer from 1993 to 2001. Charts were divided into the colostomy group or noncolostomy group. Recurrence rates, healing times, morbidity and mortality, and number of reoperations were calculated for each group. Additionally, stoma patients were interviewed for quality of life assessment. RESULTS: Sixty-seven patients were treated during the study period (colostomy, n = 41; noncolostomy, n = 26). The majority of colostomies were performed laparoscopically, with a 9.7 percent incidence of postoperative complications. The ulcer recurrence rate was lower in the treated colostomy group (43 percent) compared with the noncolostomy group (69 percent; P < 0.05). In addition, noncolostomy patients had longer healing times (7 vs. 3 months; P < 0.05), and this group required more ulcer operations than the stoma patients did. Quality of life and bowel care were much improved by the colostomy. CONCLUSIONS: Stoma construction is a safe procedure with low morbidity and mortality that helps heal pressure ulcers and decreases the incidence of recurrence. Additionally, laparoscopic stoma construction represents a technical advance that may reduce operative complications that have been previously reported with open fecal diversion.

Authors
de la Fuente, SG; Levin, LS; Reynolds, JD; Olivares, C; Pappas, TN; Ludwig, KA; Mantyh, CR
MLA Citation
de la Fuente, SG, Levin, LS, Reynolds, JD, Olivares, C, Pappas, TN, Ludwig, KA, and Mantyh, CR. "Elective stoma construction improves outcomes in medically intractable pressure ulcers." Dis Colon Rectum 46.11 (November 2003): 1525-1530.
PMID
14605574
Source
pubmed
Published In
Diseases of the Colon and Rectum
Volume
46
Issue
11
Publish Date
2003
Start Page
1525
End Page
1530
DOI
10.1097/01.DCR.0000093641.57817.12

Loop ileostomy closure at an ambulatory surgery facility: A safe and cost-effective alternative to routine hospitalization (vol 46, pg 486, 2003)

Authors
Kalady, MF; Fields, RC; Klein, S; Nielson, KC; Mantyh, CR; Ludwig, KA
MLA Citation
Kalady, MF, Fields, RC, Klein, S, Nielson, KC, Mantyh, CR, and Ludwig, KA. "Loop ileostomy closure at an ambulatory surgery facility: A safe and cost-effective alternative to routine hospitalization (vol 46, pg 486, 2003)." July 2003.
Source
wos-lite
Published In
Diseases of the Colon and Rectum
Volume
46
Issue
7
Publish Date
2003
Start Page
903
End Page
903

Vanilloid receptor-1 containing primary sensory neurones mediate dextran sulphate sodium induced colitis in rats.

BACKGROUND AND AIMS: The role of sensory neurones in colitis was studied by chemical denervation of primary sensory neurones as well as antagonism of the vanilloid receptor-1 (VR-1) in rats prior to administration of dextran sulphate sodium (DSS) to induce colitis. METHODS: Neonatal rats were chemically denervated by subcutaneous administration of capsaicin; controls received capsaicin vehicle only. When animals reached maturity, colitis was induced by administration of 5% DSS in drinking water for seven days. Additionally, normal adult rats were treated with a VR-1 antagonist capsazepine (CPZ) or vehicle twice daily via an enema from day 0 to day 6 of the DSS regimen. Control rats were treated with an enema infusion of vehicle and 5% DSS, or without either an enema infusion or DSS in drinking water. For both groups of rats, severity of inflammation was quantitated by disease activity index (DAI), myeloperoxidase (MPO) activity, and histological examination. RESULTS: DSS induced active colitis in all control rats with resultant epithelial ulceration, crypt shortening, and neutrophil infiltration. Both neonatal capsaicinised rats and normal adult rats treated with CPZ enemas exhibited significantly lower levels of DAI, MPO, and histological damage compared with vehicle treated rats (p< 0.05). CONCLUSIONS: Neonatal capsaicinisation and local administration of CPZ prevents intestinal inflammation in a well established model of colitis indicating that primary sensory neurones possessing VR-1 receptors are required in the propagation of colonic inflammation.

Authors
Kihara, N; de la Fuente, SG; Fujino, K; Takahashi, T; Pappas, TN; Mantyh, CR
MLA Citation
Kihara, N, de la Fuente, SG, Fujino, K, Takahashi, T, Pappas, TN, and Mantyh, CR. "Vanilloid receptor-1 containing primary sensory neurones mediate dextran sulphate sodium induced colitis in rats." Gut 52.5 (May 2003): 713-719.
PMID
12692058
Source
pubmed
Published In
Gut
Volume
52
Issue
5
Publish Date
2003
Start Page
713
End Page
719

Loop ileostomy closure at an ambulatory surgery facility: a safe and cost-effective alternative to routine hospitalization.

INTRODUCTION: Temporary loop ileostomies have become widely used in colorectal surgery. Subsequent ileostomy closure has traditionally required hospital admission with observation until return of bowel function. On the basis of clinical observation, the authors hypothesized that loop ileostomy closure may be performed safely without prolonged in-hospital observation. METHODS: A protocol for 23-hour observation after loop ileostomy closure was implemented at a single institution and applied to 28 patients at an ambulatory surgery facility. Patient outcomes were reviewed and results compared with a cohort of 30 patients undergoing loop ileostomy closure before introduction of the protocol. RESULTS: The study and control groups were statistically similar in age, gender, diseases, and duration after original operation. Twenty-eight patients underwent loop ileostomy closure, and all were discharged the following day. Two patients were admitted for nausea and vomiting within 48 hours after closure and remained in the hospital for two and four days, respectively. One of these patients was readmitted 12 days after surgery with an abdominal abscess that was drained percutaneously. The mean cost per patient in the study group was $2,665 US dollars. For the control population, the mean hospital stay was 2.9 days. Return of bowel function was delayed in two patients, resulting in prolonged hospital stays of six and eight days, respectively. Two patients were readmitted after discharge for nausea and vomiting. The mean cost per cohort patient was $3,811 US dollars. CONCLUSIONS: Patients undergoing loop ileostomy closure may be discharged safely after overnight observation without increased complications or hospital readmissions. This practice significantly reduces the use of hospital resources and decreases economic cost without compromising care.

Authors
Kalady, MF; Fields, RC; Klein, S; Nielsen, KC; Mantyh, CR; Ludwig, KA
MLA Citation
Kalady, MF, Fields, RC, Klein, S, Nielsen, KC, Mantyh, CR, and Ludwig, KA. "Loop ileostomy closure at an ambulatory surgery facility: a safe and cost-effective alternative to routine hospitalization." Dis Colon Rectum 46.4 (April 2003): 486-490.
PMID
12682542
Source
pubmed
Published In
Diseases of the Colon and Rectum
Volume
46
Issue
4
Publish Date
2003
Start Page
486
End Page
490
DOI
10.1097/01.DCR.0000059323.39037.47

Dextran sulfate sodium-induced enterocolitis is attenuated in vanilloid receptor-1 knockout mice

Authors
Fujino, K; De La Fuente, SG; Pappas, TN; Mantyh, CR
MLA Citation
Fujino, K, De La Fuente, SG, Pappas, TN, and Mantyh, CR. "Dextran sulfate sodium-induced enterocolitis is attenuated in vanilloid receptor-1 knockout mice." April 2003.
Source
wos-lite
Published In
Gastroenterology
Volume
124
Issue
4
Publish Date
2003
Start Page
A141
End Page
A142
DOI
10.1016/S0016-5085(03)80700-X

Vanilloid receptor subtype-1 deficient mice are protected from clostridium difficile toxin-A-induced intestinal edema

Authors
De La Fuente, SG; Fujino, K; Passas, TN; Mantyh, CR
MLA Citation
De La Fuente, SG, Fujino, K, Passas, TN, and Mantyh, CR. "Vanilloid receptor subtype-1 deficient mice are protected from clostridium difficile toxin-A-induced intestinal edema." April 2003.
Source
wos-lite
Published In
Gastroenterology
Volume
124
Issue
4
Publish Date
2003
Start Page
A475
End Page
A475
DOI
10.1016/S0016-5085(03)82403-4

Preoperative immune status determines anal condyloma recurrence after surgical excision.

PURPOSE: Immunosuppression is an important risk factor for anal condyloma progression; however, its effects on postoperative outcomes remain unclear. In the present study, we investigated risk factors and recurrence rates in immunocompromised patients requiring surgery for medically intractable anal condyloma. METHODS: A retrospective review was performed on 63 consecutive patients who underwent surgical intervention for medically intractable anal condyloma at a single institution. Patient cohorts included immunosuppressed patients (e.g, HIV-seropositive, leukemia, idiopathic lymphopenic syndrome, or transplant patients; n = 45) and immunocompetent patients (n = 18). Recurrence rates and time to recurrence after surgery were determined for both groups. Preoperative CD4 count and viral load within the HIV subpopulation were also determined. The majority of the patients were male (90 percent), with a median age of 36 years. RESULTS: Anal condyloma recurred in 66 percent of the immunosuppressed patients compared with 27 percent of the immunocompetent group. Recurrence time expressed in months was shorter in immunosuppressed patients than in immunocompetent patients (6.8 +/- 1.5 vs. 15 +/- 5.7 months; P< 0.05). In the subpopulation of HIV-seropositive patients, no association was found between recurrence rates and viral loads; however, CD4 counts were significantly lower in those who had recurrence than in those who did not (226 +/- 31.7 vs. 401 +/- 51.2 cells/microl; P< 0.05). CONCLUSIONS: After surgery, anal condyloma in immunosuppressed patients recurs significantly more often and within a shorter period of time than in patients with a competent immune system. Additionally, in HIV-seropositive patients, CD4 counts should be maximized to prevent early recurrence of anal condyloma.

Authors
de la Fuente, SG; Ludwig, KA; Mantyh, CR
MLA Citation
de la Fuente, SG, Ludwig, KA, and Mantyh, CR. "Preoperative immune status determines anal condyloma recurrence after surgical excision." Dis Colon Rectum 46.3 (March 2003): 367-373.
PMID
12626913
Source
pubmed
Published In
Diseases of the Colon and Rectum
Volume
46
Issue
3
Publish Date
2003
Start Page
367
End Page
373
DOI
10.1097/01.DCR.0000054699.96848.E2

Evaluation of porcine-derived small intestine submucosa as a biodegradable graft for gastrointestinal healing.

High-risk anastomoses in the gut may benefit from the application of a synthetic reinforcement to prevent an enteric leak. Recently a porcine-derived small intestine submucosa (SIS) was tested as a bioscaffold in a number of organ systems. The aim of this study was to evaluate the effectiveness of SIS in stimulating healing in the stomach. Twelve rats underwent surgical removal of a full-thickness gastric defect (1 cm) and subsequent repair with a double-layer patch of porcine-derived SIS. The graft was secured with interrupted sutures placed within 1 mm of the edge of the graft. After 21 days, the animals were killed and their stomachs harvested for histologic examination. Cross sections were processed for paraffin embedding and 4-micron sections were stained with hematoxylin and eosin. All animals survived, gained weight, and demonstrated no signs of peritonitis over the 3-week postoperative period. On postmortem examination, the defect was completely closed in all animals by granulation tissue and early fibrosis. Although most of the luminal surface of the grafted areas remained ulcerated, early regeneration of normal gastric mucosa was seen at the periphery of the defect. SIS may act as an effective scaffolding agent for intestinal mucosa and may offer protection in high-risk anastomoses.

Authors
de la Fuente, SG; Gottfried, MR; Lawson, DC; Harris, MB; Mantyh, CR; Pappas, TN
MLA Citation
de la Fuente, SG, Gottfried, MR, Lawson, DC, Harris, MB, Mantyh, CR, and Pappas, TN. "Evaluation of porcine-derived small intestine submucosa as a biodegradable graft for gastrointestinal healing." J Gastrointest Surg 7.1 (January 2003): 96-101.
PMID
12559190
Source
pubmed
Published In
Journal of Gastrointestinal Surgery
Volume
7
Issue
1
Publish Date
2003
Start Page
96
End Page
101

Short-chain fatty acids stimulate colonic transit via intraluminal 5-HT release in rats

We studied whether physiological concentration of short-chain fatty acids (SCFAs) affects colonic transit and colonic motility in conscious rats. Intraluminal administration of SCFAs (100-200 mM) into the proximal colon significantly accelerated colonic transit. The stimulatory effect of SCFAs on colonic transit was abolished by perivagal capsaicin treatment, atropine, hexamethonium, and vagotomy, but not by guanethidine. The stimulatory effect of SCFAs on colonic transit was also abolished by intraluminal pretreatment with lidocaine and a 5-hydroxytryptamine (HT)3 receptor antagonist. Intraluminal administration of SCFAs provoked contractions at the proximal colon, which migrated to the mid- and distal colon. SCFAs caused a significant increase in the luminal concentration of 5-HT of the vascularly isolated and luminally perfused rat colon ex vivo. It is suggested that the release of 5-HT from enterochromaffin cells in response to SCFAs stimulates 5-HT3 receptors located on the vagal sensory fibers. The sensory information is transferred to the vagal efferent and stimulates the release of acetylcholine from the colonic myenteric plexus, resulting in muscle contraction.

Authors
Fukumoto, S; Tatewaki, M; Yamada, T; Fujimiya, M; Mantyh, C; Voss, M; Eubanks, S; Harris, M; Pappas, TN; Takahashi, T
MLA Citation
Fukumoto, S, Tatewaki, M, Yamada, T, Fujimiya, M, Mantyh, C, Voss, M, Eubanks, S, Harris, M, Pappas, TN, and Takahashi, T. "Short-chain fatty acids stimulate colonic transit via intraluminal 5-HT release in rats." American Journal of Physiology - Regulatory Integrative and Comparative Physiology 284.5 53-5 (2003): R1269-R1276.
Source
scival
Published In
American Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume
284
Issue
5 53-5
Publish Date
2003
Start Page
R1269
End Page
R1276

Routine contrast imaging of low pelvic anastomosis before temporary stoma closure: Lack of clinical impact on patient management

Authors
Kalady, MF; Fields, RC; Wilkins, KB; Onaitis, MW; Tyler, DS; Mantyh, CR; Ludwig, K
MLA Citation
Kalady, MF, Fields, RC, Wilkins, KB, Onaitis, MW, Tyler, DS, Mantyh, CR, and Ludwig, K. "Routine contrast imaging of low pelvic anastomosis before temporary stoma closure: Lack of clinical impact on patient management." July 2002.
Source
wos-lite
Published In
Gastroenterology
Volume
123
Issue
1
Publish Date
2002
Start Page
29
End Page
29

Local application of capsazepine, a vanilloid recepter-1 (VR-1) antagonist, inhibits dextran sulfate sodium-induced colitis in rats.

Authors
Kihara, N; Fukumoto, S; De La Fuente, S; Takahashi, T; Pappas, T; Mantyh, CR
MLA Citation
Kihara, N, Fukumoto, S, De La Fuente, S, Takahashi, T, Pappas, T, and Mantyh, CR. "Local application of capsazepine, a vanilloid recepter-1 (VR-1) antagonist, inhibits dextran sulfate sodium-induced colitis in rats." April 2002.
Source
wos-lite
Published In
Gastroenterology
Volume
122
Issue
4
Publish Date
2002
Start Page
A393
End Page
A394

Complete response to neoadjuvant chemoradiation for rectal cancer does not influence survival.

BACKGROUND: Up to 30% of patients with locally advanced rectal cancer have a complete clinical or pathologic response to neoadjuvant chemoradiation. This study analyzes complete clinical and pathologic responders among a large group of rectal cancer patients treated with neoadjuvant chemoradiation. METHODS: From 1987 to 2000, 141 consecutive patients with biopsy-proven, locally advanced rectal cancer were treated with preoperative 5-fluorouracil-based chemotherapy and radiation. Clinical restaging after treatment consisted of proctoscopic examination and often computed tomography scan. One hundred forty patients then underwent operative resection, with results tracked in a database. Standard statistical methods were used to examine the outcomes of those patients with complete clinical or pathologic responses. RESULTS: No demographic differences were detected between either clinical complete and clinical partial responders or pathologic complete and pathologic partial responders. The positive predictive value of clinical restaging was 60%, and accuracy was 82%. By use of the Kaplan-Meier life table analysis, clinical complete responders had no advantage in local recurrence, disease-free survival, or overall survival rates when compared with clinical partial responders. Pathologic complete responders also had no recurrence or survival advantage when compared with pathologic partial responders. Of the 34 pathologic T0 tumors, 4 (13%) had lymph node metastases. CONCLUSIONS: Clinical assessment of complete response to neoadjuvant chemoradiation is unreliable. Micrometastatic disease persists in a proportion of patients despite pathologic complete response. Observation or local excision for patients thought to be complete responders should be undertaken with caution.

Authors
Onaitis, MW; Noone, RB; Fields, R; Hurwitz, H; Morse, M; Jowell, P; McGrath, K; Lee, C; Anscher, MS; Clary, B; Mantyh, C; Pappas, TN; Ludwig, K; Seigler, HF; Tyler, DS
MLA Citation
Onaitis, MW, Noone, RB, Fields, R, Hurwitz, H, Morse, M, Jowell, P, McGrath, K, Lee, C, Anscher, MS, Clary, B, Mantyh, C, Pappas, TN, Ludwig, K, Seigler, HF, and Tyler, DS. "Complete response to neoadjuvant chemoradiation for rectal cancer does not influence survival." Ann Surg Oncol 8.10 (December 2001): 801-806.
PMID
11776494
Source
pubmed
Published In
Annals of Surgical Oncology
Volume
8
Issue
10
Publish Date
2001
Start Page
801
End Page
806

Neoadjuvant chemoradiation for rectal cancer: analysis of clinical outcomes from a 13-year institutional experience.

OBJECTIVE: To examine clinical outcomes in patients receiving neoadjuvant chemoradiation for locally advanced rectal adenocarcinoma. SUMMARY BACKGROUND DATA: Preoperative radiation therapy, either alone or in combination with 5-fluorouracil-based chemotherapy, has proven both safe and effective in the treatment of rectal cancer. However, data are lacking regarding which subgroups of patients benefit from the therapy in terms of decreased local recurrence and increased survival rates. METHODS: A retrospective chart review was performed on 141 consecutive patients who received neoadjuvant chemoradiation (5-fluorouracil +/- cisplatin and 4,500-5,040 cGy) for biopsy-proven locally advanced adenocarcinoma of the rectum. Surgery was performed 4 to 8 weeks after completion of chemoradiation. Standard statistical methods were used to analyze recurrence and survival. RESULTS: Median follow-up was 27 months, and mean age was 59 years (range 28-81). Mean tumor distance from the anal verge was 6 cm (range 1-15). Of those staged before surgery with endorectal ultrasound or magnetic resonance imaging, 57% of stage II patients and 82% of stage III patients were downstaged. The chemotherapeutic regimens were well tolerated, and resections were performed on 140 patients. The percentage of sphincter-sparing procedures increased from 20% before 1996 to 76% after 1996. On pathologic analysis, 24% of specimens were T0. However, postoperative pathologic T stage had no effect on either recurrence or survival. Positive lymph node status predicted increased local recurrence and decreased survival. CONCLUSIONS: Neoadjuvant chemoradiation is safe, effective, and well tolerated. Postoperative lymph node status is the only independent predictor of recurrence and survival.

Authors
Onaitis, MW; Noone, RB; Hartwig, M; Hurwitz, H; Morse, M; Jowell, P; McGrath, K; Lee, C; Anscher, MS; Clary, B; Mantyh, C; Pappas, TN; Ludwig, K; Seigler, HF; Tyler, DS
MLA Citation
Onaitis, MW, Noone, RB, Hartwig, M, Hurwitz, H, Morse, M, Jowell, P, McGrath, K, Lee, C, Anscher, MS, Clary, B, Mantyh, C, Pappas, TN, Ludwig, K, Seigler, HF, and Tyler, DS. "Neoadjuvant chemoradiation for rectal cancer: analysis of clinical outcomes from a 13-year institutional experience." Ann Surg 233.6 (June 2001): 778-785.
PMID
11371736
Source
pubmed
Published In
Annals of Surgery
Volume
233
Issue
6
Publish Date
2001
Start Page
778
End Page
785

Coloplasty in low colorectal anastomosis: manometric and functional comparison with straight and colonic J-pouch anastomosis.

PURPOSE: After resection of the distal rectum with a straight reanastomosis, poor bowel function can occur. This is felt to be because of the loss of the rectal reservoir. To overcome this, a neoreservoir using a colonic J-pouch has been advocated in low colorectal and coloanal anastomosis. However, difficulties in reach, inability to fit the pouch into a narrow pelvis, and postoperative evacuation problems can make the colonic J-pouch problematic. Coloplasty is a new technique that may overcome the poor bowel function seen in the straight anastomosis and the problems of the colonic J-pouch. The purpose of this study was to compare the functional results after a low colorectal anastomosis among patients receiving a coloplasty, colonic J-pouch, or straight anastomosis. METHODS: Twenty patients underwent construction of a coloplasty with a low colorectal anastomosis. Postoperative manometry and functional outcome of these patients was compared with a matched group of 16 patients who had a colonic J-pouch and low colorectal anastomosis and 17 patients who had a straight low colorectal anastomosis. RESULTS: Maximum tolerated volume was significantly favorable in the coloplasty (mean, 116.9 ml) and colonic J-pouch group (mean, 150 ml) vs. the straight anastomosis group (mean, 83.3; P < 0.05) The compliance was also significantly favorable for the coloplasty (mean, 4.9 ml/mmHg) and the colonic J-pouch group (mean, 6.1 ml/mmHg) vs. the straight anastomosis group (mean, 3.2 ml/mmHg; P < 0.05) The coloplasty (mean, 2.6; range, 1-5) and colonic J-pouch (mean, 3.1; range, 2-6) had significantly fewer bowel movements per day than the straight anastomosis group (mean, 4.5; range, 1-8; P < 0.05). Similar complication rates were noted in the three groups. CONCLUSIONS: Patients with a coloplasty and low colorectal anastomosis seem to have similar functional outcome along with similar pouch compliance compared with patients with colonic J-pouch and low colorectal anastomosis. However, the coloplasty may provide an alternative method to the colonic J-pouch for a neorectal reservoir construction when reach or a narrow pelvis prohibits its formation. Technically it also may be easier to construct.

Authors
Mantyh, CR; Hull, TL; Fazio, VW
MLA Citation
Mantyh, CR, Hull, TL, and Fazio, VW. "Coloplasty in low colorectal anastomosis: manometric and functional comparison with straight and colonic J-pouch anastomosis." Dis Colon Rectum 44.1 (January 2001): 37-42.
PMID
11805561
Source
pubmed
Published In
Diseases of the Colon and Rectum
Volume
44
Issue
1
Publish Date
2001
Start Page
37
End Page
42

Extrinsic surgical denervation inhibits Clostridium difficile toxin A-induced enteritis in rats.

Clostridium difficile enteritis is caused by toxin A (TA) which stimulates substance P release and subsequent receptor activation. This receptor stimulation results in secretion, inflammation, and structural damage. However, it is unclear as to which subset of neurons is required to initiate substance P release following toxin stimulation. Five centimeter ileal segments were surgically denervated. After 10 days, three ileal loops were constructed in each rat: the denervated loop was injected intraluminally with 5 microg of TA and two intact loops were injected with TA or vehicle, respectively. Ileal secretion, myeloperoxidase activity, and histology were then assessed. Denervated ileal loops injected with TA had a 75% reduction in ileal secretion (P < 0.001), 92% reduction in myeloperoxidase activity (P < 0.01) and 96% reduction in histologic damage (P < 0.001) compared to innervated loops. There were no significant differences between the denervated loops injected with TA and those injected with vehicle. Extrinsic surgical denervation results in protection of ileal loops from TA enteritis. Furthermore, these results exclude the participation of intrinsic enteric nerves in TA-induced ileal damage. Finally, this suggests that extrinsic primary sensory neurons mediate the effects of intraluminal TA in the ileum.

Authors
Mantyh, CR; McVey, DC; Vigna, SR
MLA Citation
Mantyh, CR, McVey, DC, and Vigna, SR. "Extrinsic surgical denervation inhibits Clostridium difficile toxin A-induced enteritis in rats." Neurosci Lett 292.2 (October 6, 2000): 95-98.
PMID
10998557
Source
pubmed
Published In
Neuroscience Letters
Volume
292
Issue
2
Publish Date
2000
Start Page
95
End Page
98

Colonic "coloplasty": novel technique to enhance low colorectal or coloanal anastomosis.

After low colorectal or coloanal anastomosis, bowel dysfunction may exist. A colonic J-pouch has been proposed to reduce bowel dysfunction. We present an alternative technique to augment the reservoir function of the neorectum and reduce bowel dysfunction.

Authors
Fazio, VW; Mantyh, CR; Hull, TL
MLA Citation
Fazio, VW, Mantyh, CR, and Hull, TL. "Colonic "coloplasty": novel technique to enhance low colorectal or coloanal anastomosis." Dis Colon Rectum 43.10 (October 2000): 1448-1450.
PMID
11052525
Source
pubmed
Published In
Diseases of the Colon and Rectum
Volume
43
Issue
10
Publish Date
2000
Start Page
1448
End Page
1450

Extrinsic denervation inhibits Clostridium difficile toxin A-induced enteritis.

Authors
Mantyh, CR; McVey, DC; Vigna, SR
MLA Citation
Mantyh, CR, McVey, DC, and Vigna, SR. "Extrinsic denervation inhibits Clostridium difficile toxin A-induced enteritis." April 2000.
Source
wos-lite
Published In
Gastroenterology
Volume
118
Issue
4
Publish Date
2000
Start Page
A882
End Page
A882

Substance P activation of enteric neurons in response to intraluminal Clostridium difficile toxin A in the rat ileum.

BACKGROUND & AIMS: Nerves have been suggested to mediate the effects of bacterial toxins in intestinal diseases. However, the mechanisms involved are unknown. This study examined endogenous substance P (SP) activation of the substance P receptor (SPR) on enteric neurons in the rat ileum after exposure to intraluminal Clostridium difficile toxin A. METHODS: After intraluminal injection of toxin A in ileal loops, tissue was examined for pathological changes by histology and for SPR activation by immunocytochemical analysis of SP-induced SPR endocytosis. RESULTS: After toxin A administration, > 70% of enteric neurons showed SPR endocytosis and became swollen with thickened dendrites. In contrast, SPRs in control rats were largely confined to the plasma membrane. Rats denervated of primary afferent fibers with neonatal capsaicin injection and animals pretreated with a nonpeptide SPR antagonist showed few endosomal SPRs, and the pathological inflammatory effects of toxin A were ablated. CONCLUSIONS: Intraluminal toxin A causes the release of SP from primary afferent neurons: this endogenous SP then acts on enteric neurons in the submucosal and myenteric plexuses. SP is the primary mediator of an axon reflex mediating neurogenic inflammation in the intestine. SPR blockade may prove to be a novel therapy used to prevent intestinal inflammation.

Authors
Mantyh, CR; Pappas, TN; Lapp, JA; Washington, MK; Neville, LM; Ghilardi, JR; Rogers, SD; Mantyh, PW; Vigna, SR
MLA Citation
Mantyh, CR, Pappas, TN, Lapp, JA, Washington, MK, Neville, LM, Ghilardi, JR, Rogers, SD, Mantyh, PW, and Vigna, SR. "Substance P activation of enteric neurons in response to intraluminal Clostridium difficile toxin A in the rat ileum." Gastroenterology 111.5 (November 1996): 1272-1280.
PMID
8898641
Source
pubmed
Published In
Gastroenterology
Volume
111
Issue
5
Publish Date
1996
Start Page
1272
End Page
1280

Differential expression of two isoforms of the neurokinin-1 (substance P) receptor in vivo.

Recent pharmacological and biochemical studies have suggested that there may be more than one molecular form of the neurokinin-1 receptor (NK-1), a long and short isoform differing in the length of their cytoplasmic carboxyl-terminal tails, but no definitive evidence of the existence of such NK-1 receptor isoforms in tissue has been presented. To examine whether these different isoforms are expressed in vivo we have compared the distribution of high affinity substance P (SP) binding sites (visualized by autoradiography with [125I]SP), with the distribution of the C-terminal epitope of the full length receptor (visualized with a specific antibody against the extreme C-terminal sequence). The former method labels both long and short forms of the NK-1 receptor, while the latter labels only the long form of the protein. In the rat there is a close correspondence of [125I]SP binding and NK-1 immunoreactivity in the striatum, suggesting that the long isoform predominates in this tissue. In the parotid and submaxillary gland, there are very high levels of [125I]SP binding but only low levels of NK-1 immunoreactivity, suggesting that expression of the short form predominates in these tissues. These results imply that different tissues express different ratios of the two isoforms of the NK-1 receptor. This differential expression provides the theoretical basis for tissue specific pharmacological targeting of NK-1 receptors.

Authors
Mantyh, PW; Rogers, SD; Ghilardi, JR; Maggio, JE; Mantyh, CR; Vigna, SR
MLA Citation
Mantyh, PW, Rogers, SD, Ghilardi, JR, Maggio, JE, Mantyh, CR, and Vigna, SR. "Differential expression of two isoforms of the neurokinin-1 (substance P) receptor in vivo." Brain Res 719.1-2 (May 6, 1996): 8-13.
PMID
8782857
Source
pubmed
Published In
Brain Research
Volume
719
Issue
1-2
Publish Date
1996
Start Page
8
End Page
13

Differential release of substance P in the spinal cord in response to visceral versus somatosensory pain.

Authors
Mantyh, CR; Ghilardi, JR; Rogers, SD; Vigna, SR; Pappas, TN; Mantyh, PW
MLA Citation
Mantyh, CR, Ghilardi, JR, Rogers, SD, Vigna, SR, Pappas, TN, and Mantyh, PW. "Differential release of substance P in the spinal cord in response to visceral versus somatosensory pain." April 1996.
Source
wos-lite
Published In
Gastroenterology
Volume
110
Issue
4
Publish Date
1996
Start Page
A1097
End Page
A1097

Increased substance P receptor expression by blood vessels and lymphoid aggregates in Clostridium difficile-induced pseudomembranous colitis.

Pseudomembranous colitis is most often caused by toxins secreted by Clostridium difficile following bowel flora overgrowth after antibiotic use. The secretory and inflammatory effects observed in C. difficile toxin A-induced enterocolitis in the rat ileum are inhibited by CP-96,345, a substance P (SP) receptor antagonist. To determine if SP plays a role in the pathogenesis of human pseudomembranous colitis, SP receptor distribution was examined in a toxin A-positive specimen of bowel. Quantitative receptor autoradiography was used to examine SP receptors in tissue from a patient who tested positive for C. Difficile toxin. SP receptors were massively increased in small blood vessels and lymphoid aggregates in the pseudomembranous colitis bowel in comparison to control specimens. The SP binding was saturable and exhibited similar affinities for SP and CP-96,345. SP may contribute to the inflammatory response in pseudomembranous colitis via a massive increase in SP receptor antagonists may offer a novel therapeutic intervention for pseudomembranous colitis.

Authors
Mantyh, CR; Maggio, JE; Mantyh, PW; Vigna, SR; Pappas, TN
MLA Citation
Mantyh, CR, Maggio, JE, Mantyh, PW, Vigna, SR, and Pappas, TN. "Increased substance P receptor expression by blood vessels and lymphoid aggregates in Clostridium difficile-induced pseudomembranous colitis." Dig Dis Sci 41.3 (March 1996): 614-620. (Review)
PMID
8617145
Source
pubmed
Published In
Digestive Diseases and Sciences
Volume
41
Issue
3
Publish Date
1996
Start Page
614
End Page
620

Differential expression of substance P receptors in patients with Crohn's disease and ulcerative colitis.

BACKGROUND & AIMS: Although clinical and pathological differences exist between Crohn's disease (CD) and ulcerative colitis (UC), distinguishing features are often absent, making diagnosis and treatment problematic. This study evaluated the differences in the expression of substance P (SP) receptors in patients with CD or UC. METHODS: Tissue samples from patients with inflammatory bowel disease or control patients were obtained at surgery, processed for 125I-SP binding, and analyzed by quantitative autoradiography. RESULTS: Patients with CD showed a massive increase in SP receptors in lymphoid aggregates, small blood vessels, and enteric neurons of the small and large bowel relative to controls. Six of 16 CD specimens had no pathological evidence of CD yet continued to express high concentrations of SP receptors. Pathologically positive patients with UC showed high concentrations of SP receptors on colonic lymphoid aggregates and small blood vessels but not enteric neurons. No increased SP binding was evident in clinically and pathologically quiescent UC colons and normal UC ileostomy samples. CONCLUSIONS: The increased expression of SP receptors on the enteric neurons of patients with CD distinguishes CD from UC. The persistent increased SP binding in pathologically normal CD tissue may indicate a subclinical disease state. SP receptor expression may have important diagnostic, etiologic, and therapeutic usefulness in inflammatory bowel disease.

Authors
Mantyh, CR; Vigna, SR; Bollinger, RR; Mantyh, PW; Maggio, JE; Pappas, TN
MLA Citation
Mantyh, CR, Vigna, SR, Bollinger, RR, Mantyh, PW, Maggio, JE, and Pappas, TN. "Differential expression of substance P receptors in patients with Crohn's disease and ulcerative colitis." Gastroenterology 109.3 (September 1995): 850-860.
PMID
7657114
Source
pubmed
Published In
Gastroenterology
Volume
109
Issue
3
Publish Date
1995
Start Page
850
End Page
860

Receptor endocytosis and dendrite reshaping in spinal neurons after somatosensory stimulation.

In vivo somatosensory stimuli evoked the release of substance P from primary afferent neurons that terminate in the spinal cord and stimulated endocytosis of substance P receptors in rat spinal cord neurons. The distal dendrites that showed substance P receptor internalization underwent morphological reorganization, changing from a tubular structure to one characterized by swollen varicosities connected by thin segments. This internalization and dendritic structural reorganization provided a specific image of neurons activated by substance P. Thus receptor internalization can drive reversible structural changes in central nervous system neurons in vivo. Both of these processes may be involved in neuronal plasticity.

Authors
Mantyh, PW; DeMaster, E; Malhotra, A; Ghilardi, JR; Rogers, SD; Mantyh, CR; Liu, H; Basbaum, AI; Vigna, SR; Maggio, JE
MLA Citation
Mantyh, PW, DeMaster, E, Malhotra, A, Ghilardi, JR, Rogers, SD, Mantyh, CR, Liu, H, Basbaum, AI, Vigna, SR, and Maggio, JE. "Receptor endocytosis and dendrite reshaping in spinal neurons after somatosensory stimulation." Science 268.5217 (June 16, 1995): 1629-1632.
PMID
7539937
Source
pubmed
Published In
Science
Volume
268
Issue
5217
Publish Date
1995
Start Page
1629
End Page
1632

DIFFERENTIAL EXPRESSION OF SUBSTANCE-P RECEPTORS IN CROHNS-DISEASE AND ULCERATIVE-COLITIS

Authors
MANTYH, CR; BOLLINGER, RR; VIGNA, SR; PAPPAS, TN
MLA Citation
MANTYH, CR, BOLLINGER, RR, VIGNA, SR, and PAPPAS, TN. "DIFFERENTIAL EXPRESSION OF SUBSTANCE-P RECEPTORS IN CROHNS-DISEASE AND ULCERATIVE-COLITIS." April 1995.
Source
wos-lite
Published In
Gastroenterology
Volume
108
Issue
4
Publish Date
1995
Start Page
A870
End Page
A870

CHOLECYSTOKININ IS A PHYSIOLOGICAL MEDIATOR OF FAT-INDUCED LOWER ESOPHAGEAL SPHINCTER RELAXATION

Authors
CIACCIA, D; BRAZER, SR; LAWSON, DC; MANTYH, CR; LIDDLE, RA; PAPPAS, TN
MLA Citation
CIACCIA, D, BRAZER, SR, LAWSON, DC, MANTYH, CR, LIDDLE, RA, and PAPPAS, TN. "CHOLECYSTOKININ IS A PHYSIOLOGICAL MEDIATOR OF FAT-INDUCED LOWER ESOPHAGEAL SPHINCTER RELAXATION." April 1995.
Source
wos-lite
Published In
Gastroenterology
Volume
108
Issue
4
Publish Date
1995
Start Page
A584
End Page
A584
DOI
10.1016/0016-5085(95)26648-8

ALTERATIONS IN ENTERIC NEURON SUBSTANCE-P RECEPTORS IN CLOSTRIDIUM-DIFFICILE TOXIN-A-INDUCED COLITIS

Authors
LAPP, JA; MANTYH, CR; LYERLY, DM; VIGNA, SR; PAPPAS, TN
MLA Citation
LAPP, JA, MANTYH, CR, LYERLY, DM, VIGNA, SR, and PAPPAS, TN. "ALTERATIONS IN ENTERIC NEURON SUBSTANCE-P RECEPTORS IN CLOSTRIDIUM-DIFFICILE TOXIN-A-INDUCED COLITIS." April 1995.
Source
wos-lite
Published In
Gastroenterology
Volume
108
Issue
4
Publish Date
1995
Start Page
A858
End Page
A858
DOI
10.1016/0016-5085(95)27738-2

Rapid endocytosis of a G protein-coupled receptor: substance P evoked internalization of its receptor in the rat striatum in vivo.

Studies on cultured cells have shown that agonists induce several types of G protein-coupled receptors to undergo internalization. We have investigated this phenomenon in rat striatum, using substance P (SP)-induced internalization of the SP receptor (SPR) as our model system. Within 1 min of a unilateral striatal injection of SP in the anesthetized rat, nearly 60% of the SPR-immunoreactive neurons within the injection zone display massive internalization of the SPR--i.e., 20-200 SPR+ endosomes per cell body. Within the dendrites the SPR undergoes a striking translocation from the plasma membrane to endosomes, and these dendrites also undergo a morphological reorganization, changing from a structure of rather uniform diameter to one characterized by large, swollen varicosities connected by thin fibers. In both cell bodies and dendrites the number of SPR+ endosomes returns to baseline within 60 min of SP injection. The number of neurons displaying substantial endosomal SPR internalization is dependent on the concentration of injected SP, and the SP-induced SPR internalization is inhibited by the nonpeptide neurokinin 1 receptor antagonist RP-67,580. These data demonstrate that in the central nervous system in vivo, SP induces a rapid and widespread SPR internalization in the cell bodies and dendrites and a structural reorganization of the dendrites. These results suggest that many of the observations that have been made on the internalization and recycling of G protein-coupled receptors in in vitro transfected cell systems are applicable to similar events that occur in the mammalian central nervous system in vivo.

Authors
Mantyh, PW; Allen, CJ; Ghilardi, JR; Rogers, SD; Mantyh, CR; Liu, H; Basbaum, AI; Vigna, SR; Maggio, JE
MLA Citation
Mantyh, PW, Allen, CJ, Ghilardi, JR, Rogers, SD, Mantyh, CR, Liu, H, Basbaum, AI, Vigna, SR, and Maggio, JE. "Rapid endocytosis of a G protein-coupled receptor: substance P evoked internalization of its receptor in the rat striatum in vivo." Proc Natl Acad Sci U S A 92.7 (March 28, 1995): 2622-2626.
PMID
7535928
Source
pubmed
Published In
Proceedings of the National Academy of Sciences of USA
Volume
92
Issue
7
Publish Date
1995
Start Page
2622
End Page
2626

Reply

Authors
Mantyh, C; Pappas, T; Vigna, S
MLA Citation
Mantyh, C, Pappas, T, and Vigna, S. "Reply." Gastroenterology 108.6 (1995): 1954-1955.
Source
scival
Published In
Gastroenterology
Volume
108
Issue
6
Publish Date
1995
Start Page
1954
End Page
1955

How selective are the cholecystokinin antagonists in the dog? [2]

Authors
Fox-Threlkeld, JAET; Daniel, EE; Fioramonti, J; Mantyh, C; Pappas, T; Vigna, S
MLA Citation
Fox-Threlkeld, JAET, Daniel, EE, Fioramonti, J, Mantyh, C, Pappas, T, and Vigna, S. "How selective are the cholecystokinin antagonists in the dog? [2]." Gastroenterology 108.6 (1995): 1953-1955.
Source
scival
Published In
Gastroenterology
Volume
108
Issue
6
Publish Date
1995
Start Page
1953
End Page
1955

Localization of cholecystokinin A and cholecystokinin B/gastrin receptors in the canine upper gastrointestinal tract.

BACKGROUND/AIMS: Cholecystokinin (CCK) is a neuropeptide that exerts numerous effects in the gut. To determine the sites of action of CCK, the distribution and properties of CCK receptor subtypes were studied. METHODS: CCK receptors were localized by autoradiographic analysis of 125I-CCK binding to frozen sections of the canine upper gastrointestinal tract. RESULTS: In the cardiac and fundic stomach, CCK-B/gastrin receptors were found in the mucosa and in a subpopulation of neuronal elements in the circular muscle. The antrum expressed CCK-B/gastrin receptors in a few neurons in the circular muscle and in the entire myenteric plexus; no receptors were observed in the antral mucosa or esophagus. The duodenum showed a high concentration of CCK-B/gastrin receptors in the myenteric plexus. The cardiac and fundic basal mucosae expressed CCK-A receptors. Two nonpeptide CCK receptor antagonists were unable to differentiate between the receptor subtypes. CONCLUSIONS: The differential expression of CCK receptor subtypes in the gastric mucosa provides a morphological basis for the separate regulatory roles of CCK and gastrin in gastric function. CCK-B/gastrin receptor expression in a subset of neurons in gastric circular muscle suggests a novel site of action for CCK and/or gastrin.

Authors
Mantyh, CR; Pappas, TN; Vigna, SR
MLA Citation
Mantyh, CR, Pappas, TN, and Vigna, SR. "Localization of cholecystokinin A and cholecystokinin B/gastrin receptors in the canine upper gastrointestinal tract." Gastroenterology 107.4 (October 1994): 1019-1030.
PMID
7926455
Source
pubmed
Published In
Gastroenterology
Volume
107
Issue
4
Publish Date
1994
Start Page
1019
End Page
1030

Substance P binding sites on intestinal lymphoid aggregates and blood vessels in inflammatory bowel disease correspond to authentic NK-1 receptors.

Previous reports have described the ectopic expression of substance P binding sites on lymphoid aggregates and small blood vessels in inflammatory bowel disease. In this report, three non-peptide NK-1 receptor antagonists, CP-96,345, RP-67,580, and L-703,606 abolished saturable 125I-Bolton-Hunter substance P binding to the ectopically expressed receptors in frozen sections of surgically resected bowel from five patients with either Crohn's disease or ulcerative colitis. The rank order of affinity was approximately substance P approximately CP-96,345 approximately L-703,606 > RP-67,580. These results suggest that: (i) the ectopically expressed substance P binding sites in inflammatory bowel disease are authentic NK-1 receptors, (ii) all ectopically expressed receptors on small blood vessels, and lymphoid aggregates as well as normally expressed receptors on the bowel circular muscle have similar receptor affinities and specificities for substance P and the non-peptide antagonists, and (iii) non-peptide antagonists may be therapeutically beneficial in inflammatory bowel disease by inhibiting the pro-inflammatory effects of substance P acting via the NK-1 receptor.

Authors
Mantyh, CR; Vigna, SR; Maggio, JE; Mantyh, PW; Bollinger, RR; Pappas, TN
MLA Citation
Mantyh, CR, Vigna, SR, Maggio, JE, Mantyh, PW, Bollinger, RR, and Pappas, TN. "Substance P binding sites on intestinal lymphoid aggregates and blood vessels in inflammatory bowel disease correspond to authentic NK-1 receptors." Neurosci Lett 178.2 (September 12, 1994): 255-259.
PMID
7529913
Source
pubmed
Published In
Neuroscience Letters
Volume
178
Issue
2
Publish Date
1994
Start Page
255
End Page
259

Effect of CGRP antagonist, alpha-CGRP 8-37, on acid secretion in the dog.

The recently synthesized calcitonin gene-related peptide (CGRP) antagonist, human alpha-CGRP 8-37, was used to study its effects on gastric acid secretion. Four dogs with gastric fistula were used to measure the antagonist's physiologic effects in the stomach. All dogs received a bactopeptone dextrose meal (intragastric titration to pH 5.5) with either continuous CGRP 8-37 (1000 pmol/kg/hr) or saline (control). Additionally, intravenous bombesin (75-600 ng/kg/hr) and bethanechol (12.5-100 micrograms/kg/hr) was tested in the presence of the antagonist. Plasma gastrin levels also were measured via radioimmunoassay (RIA) in control and CGRP 8-37-stimulated animals. Gastric acid secretion increased by 100% with infusion of 1000 pmol/kg/hr CGRP 8-37 when compared to the control. Acid output increased 98% with both intravenous antagonist and 600 ng/kg/hr bombesin when compared to bombesin alone. However, no augmentation of acid secretion by CGRP 8-37 was shown with 25 micrograms/kg/hr bethanechol. RIA of plasma gastrin demonstrated no effect with the antagonist when given alone and did not increase bombesin-stimulated gastrin release. We conclude that CGRP 8-37 blocks native CGRP inhibitory effects on gastric acid secretion. Our findings of potentiation of acid secretion by bombesin as well as no change in gastrin levels in the presence of the antagonist is likely due to a blockage in a noncholinergic neuron to the somatostatin cell. Furthermore, CGRP 8-37 did not increase bethanechol-stimulated acid secretion, most likely due to bethanechol's (acetylcholine) nearly ubiquitous positive effects on acid secretion.

Authors
Lawson, DC; Mantyh, CR; Pappas, TN
MLA Citation
Lawson, DC, Mantyh, CR, and Pappas, TN. "Effect of CGRP antagonist, alpha-CGRP 8-37, on acid secretion in the dog." Dig Dis Sci 39.7 (July 1994): 1405-1408.
PMID
7913011
Source
pubmed
Published In
Digestive Diseases and Sciences
Volume
39
Issue
7
Publish Date
1994
Start Page
1405
End Page
1408

SUBSTANCE-P RECEPTOR EXPRESSION AND RECEPTOR ANTAGONISTS IN HUMAN INFLAMMATORY BOWEL-DISEASE (IBD) AND RAT ENTEROCOLITIS

Authors
MANTYH, CR; VIGNA, SR; MAGGIO, JE; MANTYH, PW; SARTOR, RB; PAPPAS, TN
MLA Citation
MANTYH, CR, VIGNA, SR, MAGGIO, JE, MANTYH, PW, SARTOR, RB, and PAPPAS, TN. "SUBSTANCE-P RECEPTOR EXPRESSION AND RECEPTOR ANTAGONISTS IN HUMAN INFLAMMATORY BOWEL-DISEASE (IBD) AND RAT ENTEROCOLITIS." April 1994.
Source
wos-lite
Published In
Gastroenterology
Volume
106
Issue
4
Publish Date
1994
Start Page
A728
End Page
A728

LOCALIZATION OF CCK(A) AND CCK(B)/GASTRIN RECEPTORS IN THE CANINE UPPER GASTROINTESTINAL-TRACT

Authors
MANTYH, CR; VIGNA, SR; PAPPAS, TN
MLA Citation
MANTYH, CR, VIGNA, SR, and PAPPAS, TN. "LOCALIZATION OF CCK(A) AND CCK(B)/GASTRIN RECEPTORS IN THE CANINE UPPER GASTROINTESTINAL-TRACT." April 1994.
Source
wos-lite
Published In
Gastroenterology
Volume
106
Issue
4
Publish Date
1994
Start Page
A825
End Page
A825

Bombesin/GRP-preferring and neuromedin B-preferring receptors in the rat urogenital system.

Bombesin binding sites were localized in the rat urogenital system by autoradiography of 125I-Tyr4-bombesin binding to frozen tissue sections. Saturable binding was observed in the bladder, seminal vesicle, uterus, and oviduct. In all organs, the binding sites corresponded to layers of smooth muscle. Radioligand binding studies were performed on homogenized membrane preparations from bladder, uterus, and seminal vesicle. Membrane binding was saturable, reversible, time- and temperature-dependent, and specific for bombesin and related peptides. Analysis of saturable equilibrium binding from all three organs yielded a best fit to a one-site model of high affinity binding with apparent KdS of 720 pM for bladder, 470 pM for uterus, and 700 pM for seminal vesicle. Neuromedin B was potent in displacing saturable 125I-Tyr4-bombesin binding from bladder and seminal vesicle but not uterus membranes. In order to characterize these binding sites further, the ability of these membranes to interact with a specific bombesin receptor antagonist, [Leu13-psi-CH2NH-Leu14]-bombesin, and with GTP-gamma-S was determined. [Leu13-psi-CH2NH-Leu14]-bombesin was much more potent in displacing saturable 125I-Tyr4-bombesin binding from uterus than from bladder and seminal vesicle membranes, further supporting the distinction between the uterus and the bladder/seminal vesicle binding sites as bombesin receptor subtypes. GTP-gamma-S inhibited saturable 125I-Tyr4-bombesin binding to membranes from all three organs, indicating that both receptor subtypes are linked to GTP-binding proteins. We conclude that smooth muscle in the rat urogenital system expresses bombesin receptors and that endogenous GRP and neuromedin B may regulate some reproductive and excretory functions. The bladder and seminal vesicle express the neuromedin B-preferring subtype and the uterus expresses the bombesin/GRP-preferring subtype of bombesin receptor.

Authors
Kilgore, WR; Mantyh, PW; Mantyh, CR; McVey, DC; Vigna, SR
MLA Citation
Kilgore, WR, Mantyh, PW, Mantyh, CR, McVey, DC, and Vigna, SR. "Bombesin/GRP-preferring and neuromedin B-preferring receptors in the rat urogenital system." Neuropeptides 24.1 (January 1993): 43-52.
PMID
8381528
Source
pubmed
Published In
Neuropeptides
Volume
24
Issue
1
Publish Date
1993
Start Page
43
End Page
52

Glomerular atrial natriuretic factor receptors in primary glomerulopathies: studies on human renal biopsies.

Human renal biopsies are currently used to provide information about morphologic changes, chronicity of disease, patterns of inflammation, and immunoglobulin deposition. This practice has provided only limited insight into functional aberrations and has failed to provided information necessary for disease classification based on pathophysiology. To expand the potential of the renal biopsy in this regard and to determine whether differences in glomerular atrial natriuretic factor (ANF) binding exist in different forms of primary renal disease, quantitative autoradiography and 125I-human ANF (1-28) were used to determine the location and pharmacological characteristics of ANF binding sites in the normal human kidney. Specific ANF binding was highest in the glomeruli, but lower levels of specific binding were localized to the inner medulla and the interlobular arteries. ANF binding sites in the human kidney were found to be highly stable and similar in both location and pharmacology to those observed in experimental animals. As determined by saturation experiments, the equilibrium dissociation constants for glomeruli, inner medulla, and interlobular arteries were almost identical at 4.0 x 10(-11) mol/L. Competitive binding inhibition studies with unlabeled human ANF (1-28) demonstrated highly specific binding shared by the glomerulus, inner medulla, and interlobular artery, with apparent half-maximal inhibition concentrations of 9.2 x 10(-10) mol/L, 8.0 x -10 mol/L, and 8.2 x 10(-10) mol/L, respectively. Quantitation of specific binding of ANF to glomeruli in needle biopsy specimens of three primary glomerulopathies, ie, minimal-change disease, membranous nephropathy, and focal glomerulosclerosis, showed no differences among the groups. This study demonstrates the feasibility of studying receptor physiology on biopsy specimens of the human kidney and should allow renal diseases, particularly of glomerular origin, to be characterized according to differences in hormone binding and hormone responsiveness. The absence of significant differences in glomerular ANF binding in the primary glomerulopathies studied is consistent with other studies that have failed to delineate important pathophysiological differences in renal function and volume homeostasis in these disease states.

Authors
Bacay, AC; Mantyh, CR; Cohen, AH; Mantyh, PW; Fine, LG
MLA Citation
Bacay, AC, Mantyh, CR, Cohen, AH, Mantyh, PW, and Fine, LG. "Glomerular atrial natriuretic factor receptors in primary glomerulopathies: studies on human renal biopsies." Am J Kidney Dis 14.5 (November 1989): 386-395.
PMID
2554728
Source
pubmed
Published In
American Journal of Kidney Diseases
Volume
14
Issue
5
Publish Date
1989
Start Page
386
End Page
395

Substance P receptors on canine chief cells: localization, characterization, and function.

Saturable binding sites for 125I-Bolton-Hunter substance P were observed in frozen sections of the oxyntic mucosa of the canine stomach using quantitative autoradiography. The cell type possessing substance P binding sites in this region was identified as the chief cell in 2 ways. First, the saturable binding of radioiodinated substance P correlated with chief cell content (and not with parietal cell content, for example) in dispersed oxyntic mucosal cells fractionated by centrifugal elutriation. Second, saturable binding of radioiodinated substance P was localized to dispersed chief cells by autoradiography using emulsion-coated preparations of isolated cells affixed to glass slides. Parietal and mucous cells did not bind substance P. In studies of enriched chief cell preparations, the binding of radiolabeled substance P was found to be time- and cell number-dependent, specific, saturable, reversible, and of high affinity. Equilibrium binding analysis revealed a single class of binding sites with an apparent Kd of 105 pM and a Bmax of 3000 receptors per cell. In competitive displacement studies, the order of potency of analogs for inhibition of the saturable binding of radiolabeled substance P to chief cells was substance P = physalaemin greater than substance K greater than neuromedin K; thus, the chief cell has a substance P-preferring tachykinin binding site. Bombesin, cholecystokinin, and somatostatin had no effect on substance P binding. Substance P stimulated pepsinogen secretion from isolated canine oxyntic glands in dose-dependent fashion with a half-maximal response occurring at a substance P dose of about 1 mM.(ABSTRACT TRUNCATED AT 250 WORDS)

Authors
Vigna, SR; Mantyh, CR; Soll, AH; Maggio, JE; Mantyh, PW
MLA Citation
Vigna, SR, Mantyh, CR, Soll, AH, Maggio, JE, and Mantyh, PW. "Substance P receptors on canine chief cells: localization, characterization, and function." J Neurosci 9.8 (August 1989): 2878-2886.
PMID
2475593
Source
pubmed
Published In
The Journal of neuroscience : the official journal of the Society for Neuroscience
Volume
9
Issue
8
Publish Date
1989
Start Page
2878
End Page
2886

Receptors for sensory neuropeptides in human inflammatory diseases: implications for the effector role of sensory neurons.

Glutamate and several neuropeptides are synthesized and released by subpopulations of primary afferent neurons. These sensory neurons play a role in regulating the inflammatory and immune responses in peripheral tissues. Using quantitative receptor autoradiography we have explored what changes occur in the location and concentration of receptor binding sites for sensory neurotransmitters in the colon in two human inflammatory diseases, ulcerative colitis and Crohn's disease. The sensory neurotransmitter receptors examined included bombesin, calcitonin gene related peptide-alpha, cholecystokinin, galanin, glutamate, somatostatin, neurokinin A (substance K), substance P, and vasoactive intestinal polypeptide. Of the nine receptor binding sites examined only substance P binding sites associated with arterioles, venules and lymph nodules were dramatically up-regulated in the inflamed tissue. These data suggest that substance P is involved in regulating the inflammatory and immune responses in human inflammatory diseases and indicate a specificity of efferent action for each sensory neurotransmitter in peripheral tissues.

Authors
Mantyh, PW; Catton, MD; Boehmer, CG; Welton, ML; Passaro, EP; Maggio, JE; Vigna, SR
MLA Citation
Mantyh, PW, Catton, MD, Boehmer, CG, Welton, ML, Passaro, EP, Maggio, JE, and Vigna, SR. "Receptors for sensory neuropeptides in human inflammatory diseases: implications for the effector role of sensory neurons." Peptides 10.3 (May 1989): 627-645.
PMID
2550912
Source
epmc
Published In
Peptides
Volume
10
Issue
3
Publish Date
1989
Start Page
627
End Page
645
DOI
10.1016/0196-9781(89)90154-x

Autoradiographic localization and characterization of tachykinin receptor binding sites in the rat brain and peripheral tissues.

Quantitative receptor autoradiography using several radiolabeled tachykinins was used to localize and characterize tachykinin peptide receptor binding sites in rat CNS and peripheral tissues. Autoradiographic localization and displacement experiments using several radiolabeled tachykinins indicate that in the rat there are at least 3 distinct tachykinin receptor binding sites. One of these is present in both the CNS and peripheral tissues, one is present only in the CNS, and one is present only in peripheral tissues. The first tachykinin receptor binding site, which is detectable in both the CNS and peripheral tissues, appears to prefer substance P (SP) as an endogenous ligand. Areas expressing high concentrations of this binding site include the medial septum, superior colliculus, inferior olive, inner plexiform layer of the retina, external muscle of the bladder, and the muscularis externa of the esophagus. The second type of tachykinin receptor binding site, which is detectable only in the CNS appears to prefer either neuromedin K (NK) and/or substance K (SK) as the endogenous ligand. This receptor binding site is labeled by Bolton-Hunter conjugates of NK, SK, eledoisin, or kassinin and is found in high concentrations in laminae 4 and 5 of the cerebral cortex, the ventral tegmental area, laminae 1 and 2 of the spinal cord, and the inner plexiform layer of the retina. The third type of tachykinin receptor binding site is detectable only in peripheral tissues and appears to prefer SK as the endogenous ligand. This receptor binding site is labeled by SK, eledoisin, or kassinin radioligands and tissues that express high concentrations include the muscularis mucosae of the esophagus, the circular muscle of the colon, and the external muscle of the bladder. These data suggest that SP receptors are expressed in the brain and peripheral tissues, NK receptors are expressed in the CNS, and SK receptors are expressed in peripheral tissue. These data fit well with radioimmunoassay data that suggest that, whereas in the CNS SP, SK and NK are present in high concentrations, in peripheral tissues only SP and SK are present in detectable concentrations. The present classification of tachykinin receptors places a lower limit on the number of mammalian tachykinin receptor types and provides a functional/morphological framework for exploring the diverse actions of tachykinin peptides in both the CNS and peripheral tissues.

Authors
Mantyh, PW; Gates, T; Mantyh, CR; Maggio, JE
MLA Citation
Mantyh, PW, Gates, T, Mantyh, CR, and Maggio, JE. "Autoradiographic localization and characterization of tachykinin receptor binding sites in the rat brain and peripheral tissues." J Neurosci 9.1 (January 1989): 258-279.
PMID
2536418
Source
pubmed
Published In
The Journal of neuroscience : the official journal of the Society for Neuroscience
Volume
9
Issue
1
Publish Date
1989
Start Page
258
End Page
279

GLOMERULAR ATRIAL NATRIURETIC FACTOR (ANF) RECEPTORS IN PRIMARY GLOMERULOPATHIES - STUDIES ON HUMAN RENAL BIOPSIES

Authors
BACAY, AC; MANTYH, CR; COHEN, AH; MANTYH, PW; FINE, LG
MLA Citation
BACAY, AC, MANTYH, CR, COHEN, AH, MANTYH, PW, and FINE, LG. "GLOMERULAR ATRIAL NATRIURETIC FACTOR (ANF) RECEPTORS IN PRIMARY GLOMERULOPATHIES - STUDIES ON HUMAN RENAL BIOPSIES." January 1989.
Source
wos-lite
Published In
Kidney international
Volume
35
Issue
1
Publish Date
1989
Start Page
207
End Page
207

Calcitonin gene-related peptide-alpha receptor binding sites in the gastrointestinal tract.

Calcitonin gene-related peptide-alpha (CGRP alpha) is a putative neurotransmitter in the brain and in peripheral tissues. Quantitative receptor autoradiography was used to localize and quantify the distribution of specific binding sites for radiolabeled human CGRP alpha in the canine gastrointestinal tract. The canine gastrointestinal tract was chosen as a model since it is similar in both size and structure to the human gastrointestinal tract. In the stomach CGRP alpha binding sites were localized to smooth muscle cells in the muscularis mucosa and muscularis externa, the smooth muscle and endothelium of medium and small arteries, neurons in the myenteric plexus, mucosal epithelial cells and the germinal centers of lymph nodules. In the intestines, the prominent cells types expressing CGRP alpha receptors were myenteric neurons and the germinal centers of lymph nodules. Since previous studies have demonstrated that CGRP-containing sensory neurons innervate the muscularis externa in the stomach and since CGRP alpha receptors are expressed by smooth muscle cells in the muscularis externa, these results suggest that sensory neurons may directly regulate gastric motility by releasing CGRP. In correlation with previous physiological data, the present study suggests that CGRP is involved in the regulation of a variety of gastrointestinal functions including gastric motility, mucosal ion transport, hemodynamics, digestive enzyme secretion, neuronal excitability, and the inflammatory and immune response.

Authors
Gates, TS; Zimmerman, RP; Mantyh, CR; Vigna, SR; Mantyh, PW
MLA Citation
Gates, TS, Zimmerman, RP, Mantyh, CR, Vigna, SR, and Mantyh, PW. "Calcitonin gene-related peptide-alpha receptor binding sites in the gastrointestinal tract." Neuroscience 31.3 (1989): 757-770.
PMID
2556661
Source
pubmed
Published In
Neuroscience
Volume
31
Issue
3
Publish Date
1989
Start Page
757
End Page
770

Vasoactive intestinal polypeptide receptor binding sites in the human gastrointestinal tract: localization by autoradiography.

Vasoactive intestinal polypeptide (VIP) is a putative neurotransmitter in both the brain and peripheral tissues. To define possible target tissues of VIP we have used quantitative receptor autoradiography to localize and quantify the distribution of [125I]VIP receptor binding sites in histologically normal human surgical specimens. While the distribution of VIP binding sites was different for each gastrointestinal segment examined, specific vasoactive intestinal polypeptide binding sites were localized to the mucosa, the muscularis mucosa, the smooth muscle of submucosal arterioles, the circular and longitudinal smooth muscle of the muscularis externa, the myenteric plexus, and lymph nodules. In most segments, the mucosal layer expressed the highest concentration of VIP binding sites, with the duodenal and jejunal mucosa showing the highest density of receptors. These results identify putative VIP target tissues in the human gastrointestinal tract. In correlation with physiological data, VIP binding sites appear to be involved in the regulation of a variety of gastrointestinal functions including mucosal ion transport, gastric secretion, hemodynamic regulation, gastric and intestinal motility, neuronal excitability, and modulation of the immune system.

Authors
Zimmerman, RP; Gates, TS; Mantyh, CR; Vigna, SR; Welton, ML; Passaro, EP; Mantyh, PW
MLA Citation
Zimmerman, RP, Gates, TS, Mantyh, CR, Vigna, SR, Welton, ML, Passaro, EP, and Mantyh, PW. "Vasoactive intestinal polypeptide receptor binding sites in the human gastrointestinal tract: localization by autoradiography." Neuroscience 31.3 (1989): 771-783.
PMID
2556662
Source
pubmed
Published In
Neuroscience
Volume
31
Issue
3
Publish Date
1989
Start Page
771
End Page
783

Localization of bombesin receptors in the human gastrointestinal tract using quantitative receptor autoradiography

Authors
Welton, ML; Mantyh, CR; Gates, TS; Popper, P; Vigna, SR; Maggio, JE; Jr, EP; Mantyh, PW
MLA Citation
Welton, ML, Mantyh, CR, Gates, TS, Popper, P, Vigna, SR, Maggio, JE, Jr, EP, and Mantyh, PW. "Localization of bombesin receptors in the human gastrointestinal tract using quantitative receptor autoradiography." Annals of the New York Academy of Sciences 547 (1989): 468-470.
Source
scival
Published In
Annals of the New York Academy of Sciences
Volume
547
Publish Date
1989
Start Page
468
End Page
470

Calcitonin gene-related peptide (CGRP) in the rat central nervous system: patterns of immunoreactivity and receptor binding sites.

The distribution of immunoreactive (IR) axons and neurons in the rat central nervous system (CNS) has been studied with an antiserum directed against the C-terminal sequence of rat a-calcitonin gene-related peptide (CGRP) and a durable peroxidase reaction product for detailed analysis in relation to normal cytoarchitecture. These materials were studied and illustrated in the three principal axes in relation to cell-stained adjacent sections in normal as well as colchicine- and capsaicin-treated animals, although no fundamental differences in pattern were evident in neurotoxin-treated rats. The patterns of CGRP-IR were then compared with autoradiograms of specific, high affinity receptor binding sites for 125I-human a-CGRP. CGRP-IR labeling in motor systems includes the vast majority of motoneurons, enabling facile identification of isolated 'accessory' populations. Preganglionic parasympathetic nuclei revealed only labeling of a small proportion of neurons. By contrast, the sensory systems revealed a diversity of labeling patterns precluding simple generalizations. Peripheral input ranges from extensive labeling of thin somatic afferents, feeble to moderate gustatory and olfactory afferents to a total absence of auditory afferents, yet IR axons and neurons can be found in selective distribution within each of these sensory systems. Patterns of IR in various integrative centers, e.g. cerebellum, basal ganglia and hypothalamus, reveal selectivity that fails to conform to conventional descriptions of functional systems. Some regions display unexpected patterns, e.g. vertical stripes in cerebellar cortex. CGRP receptor binding sites (RB) are found in many of the sites where IR axons terminate and in some cases, e.g. motor neurons, which express intraneuronal IR. The main sensory systems reveal a variety of RB patterns, only a few of which can be related to sites of IR axon terminals. Many apparent 'mismatches' between IR and RB are illustrated and discussed in the context of functional peptide expression or in quasi-hormonal terms. It is suggested that the principle of CGRP-IR axon distribution in peripheral tissues, where synapses are lacking, might also apply to the CNS and that neither the locus of IR-axon terminals nor RB sites need indicate transmitter action for impulse information transfer. CGRP is a widely distributed neuromodulator probably subserving a role in both synaptic and metabolic regulation, depending on the specific requirements of the diverse distribution of its receptors.

Authors
Kruger, L; Mantyh, PW; Sternini, C; Brecha, NC; Mantyh, CR
MLA Citation
Kruger, L, Mantyh, PW, Sternini, C, Brecha, NC, and Mantyh, CR. "Calcitonin gene-related peptide (CGRP) in the rat central nervous system: patterns of immunoreactivity and receptor binding sites." Brain Res 463.2 (November 1, 1988): 223-244.
PMID
2848610
Source
pubmed
Published In
Brain Research
Volume
463
Issue
2
Publish Date
1988
Start Page
223
End Page
244

Substance P and substance K receptor binding sites in the human gastrointestinal tract: localization by autoradiography.

Quantitative receptor autoradiography was used to localize and quantify the distribution of binding sites for 125I-radiolabeled substance P (SP), substance K (SK) and neuromedin K (NK) in the human GI tract using histologically normal tissue obtained from uninvolved margins of resections for carcinoma. The distribution of SP and SK binding sites is different for each gastrointestinal (GI) segment examined. Specific SP binding sites are expressed by arterioles and venules, myenteric plexus, external circular muscle, external longitudinal muscle, muscularis mucosa, epithelial cells of the mucosa, and the germinal centers of lymph nodules. SK binding sites are distributed in a pattern distinct from SP binding sites and are localized to the external circular muscle, external longitudinal muscle, and the muscularis mucosa. Binding sites for NK were not detected in any part of the human GI tract. These results demonstrate that: 1) surgical specimens from the human GI tract can be effectively processed for quantitative receptor autoradiography; 2) of the three mammalian tachykinins tested, SP and SK, but not NK binding sites are expressed in detectable levels in the human GI tract; 3) whereas SK receptor binding sites are expressed almost exclusively by smooth muscle, SP binding sites are expressed by smooth muscle cells, arterioles, venules, epithelial cells of the mucosa and cells associated with lymph nodules; and 4) both SP and SK binding sites expressed by smooth muscle are more stable than SP binding sites expressed by blood vessels, lymph nodules, and mucosal cells.

Authors
Gates, TS; Zimmerman, RP; Mantyh, CR; Vigna, SR; Maggio, JE; Welton, ML; Passaro, EP; Mantyh, PW
MLA Citation
Gates, TS, Zimmerman, RP, Mantyh, CR, Vigna, SR, Maggio, JE, Welton, ML, Passaro, EP, and Mantyh, PW. "Substance P and substance K receptor binding sites in the human gastrointestinal tract: localization by autoradiography." Peptides 9.6 (November 1988): 1207-1219.
PMID
2470062
Source
pubmed
Published In
Peptides
Volume
9
Issue
6
Publish Date
1988
Start Page
1207
End Page
1219

Vasoactive intestinal peptide (VIP) receptors in the canine gastrointestinal tract.

Vasoactive intestinal peptide (VIP) is a putative neurotransmitter in both the brain and peripheral tissues. To define possible target tissues of VIP we have used quantitative receptor autoradiography to localize and quantify the distribution of 125I-VIP receptor binding sites in the canine gastrointestinal tract. While the distribution of VIP binding sites was different for each segment examined, specific VIP binding sites were localized to the mucosa, the muscularis mucosa, the smooth muscle of submucosal arterioles, lymph nodules, and the circular and longitudinal smooth muscle of the muscularis externa. These results identify putative target tissues of VIP action in the canine gastrointestinal tract. In correlation with physiological data, VIP sites appear to be involved in the regulation of a variety of gastrointestinal functions including epithelial ion transport, gastric secretion, hemodynamic regulation, immune response, esophageal, gastric and intestinal motility.

Authors
Zimmerman, RP; Gates, TS; Mantyh, CR; Vigna, SR; Boehmer, CG; Mantyh, PW
MLA Citation
Zimmerman, RP, Gates, TS, Mantyh, CR, Vigna, SR, Boehmer, CG, and Mantyh, PW. "Vasoactive intestinal peptide (VIP) receptors in the canine gastrointestinal tract." Peptides 9.6 (November 1988): 1241-1253.
PMID
2854625
Source
pubmed
Published In
Peptides
Volume
9
Issue
6
Publish Date
1988
Start Page
1241
End Page
1253

Receptor binding sites for atrial natriuretic factor are expressed by brown adipose tissue.

To explore the possibility that atrial natriuretic factor (ANF) is involved in thermoregulation we used quantitative receptor autoradiography and homogenate receptor binding assays to identify ANF bindings sites in neonatal rat and sheep brown adipose tissue, respectively. Using quantitative receptor autoradiography were were able to localize high levels of specific binding sites for 125I-rat ANF in neonatal rat brown adipose tissue. Homogenate binding assays on sheep brown fat demonstrated that the radioligand was binding to the membrane fraction and that the specific binding was not due to a lipophilic interaction between 125I-rat ANF and brown fat. Specific binding of 125I-rat ANF to the membranes of brown fat cells was inhibited by unlabeled rat ANF with a Ki of 8.0 x 10(-9) M, but not by unrelated peptides. These studies demonstrate that brown fat cells express high levels of ANF receptor binding sites in neonatal rat and sheep and suggest that ANF may play a role in thermoregulation.

Authors
Bacay, AC; Mantyh, CR; Vigna, SR; Mantyh, PW
MLA Citation
Bacay, AC, Mantyh, CR, Vigna, SR, and Mantyh, PW. "Receptor binding sites for atrial natriuretic factor are expressed by brown adipose tissue." Peptides 9.5 (September 1988): 1021-1026.
PMID
2854242
Source
pubmed
Published In
Peptides
Volume
9
Issue
5
Publish Date
1988
Start Page
1021
End Page
1026

Receptor binding sites for substance P and substance K in the canine gastrointestinal tract and their possible role in inflammatory bowel disease.

The mammalian tachykinins, substance P, substance K (neurokinin A) and neuromedin K (neurokinin B), are putative peptide neurotransmitters in both the brain and peripheral tissues. We used quantitative receptor autoradiography to localize and quantify the distribution of binding sites for radiolabeled substance P, substance K and neuromedin K in the canine gastrointestinal tract. Substance P binding sites were localized to smooth muscle cells in the muscularis mucosa and muscularis externa, the smooth muscle and endothelium of arterioles and venules, neurons in the myenteric plexus, mucosal epithelial cells, exocrine cells and lymph nodules. Substance K binding sites were distributed in a pattern distinct from substance P binding sites and were localized to smooth muscle cells in the muscularis mucosa and muscularis externa, the smooth muscle and endothelium of arterioles and venules, and neurons of the myenteric plexus. Neuromedin K binding sites were not observed in any area of the canine gastrointestinal tract although they were localized with high specific/non-specific binding ratios in the canine spinal cord. These results indicate that there are at least two distinct types of tachykinin receptor binding sites in the canine gastrointestinal tract, one of which probably recognizes substance P and the other substance K as endogenous ligands. In correlation with previous physiological data, these substance P and substance K receptor binding sites appear to be involved in the regulation of a variety of gastrointestinal functions including gastric motility, mucosal ion transport, hemodynamics, digestive enzyme secretion and neuronal excitability. In addition these results demonstrate that receptor binding sites for substance P and substance K are expressed by cells involved in mediating inflammatory and immune responses. These data, together with our studies on surgical specimens from patients with inflammatory bowel disease, suggest that in a pathophysiological state tachykinins and their receptors may play a role in inflammatory bowel disease and should permit a rational approach to designing neuropeptide antagonists which may prove effective in treating inflammatory diseases.

Authors
Mantyh, PW; Mantyh, CR; Gates, T; Vigna, SR; Maggio, JE
MLA Citation
Mantyh, PW, Mantyh, CR, Gates, T, Vigna, SR, and Maggio, JE. "Receptor binding sites for substance P and substance K in the canine gastrointestinal tract and their possible role in inflammatory bowel disease." Neuroscience 25.3 (June 1988): 817-837.
PMID
2457186
Source
pubmed
Published In
Neuroscience
Volume
25
Issue
3
Publish Date
1988
Start Page
817
End Page
837

Receptor binding sites for substance P, but not substance K or neuromedin K, are expressed in high concentrations by arterioles, venules, and lymph nodules in surgical specimens obtained from patients with ulcerative colitis and Crohn disease.

Several lines of evidence indicate that tachykinin neuropeptides [substance P (SP), substance K (SK), and neuromedin K (NK)] play a role in regulating the inflammatory and immune responses. To test this hypothesis in a human inflammatory disease, quantitative receptor autoradiography was used to examine possible abnormalities in tachykinin binding sites in surgical specimens from patients with inflammatory bowel disease. Surgical specimens of colon were obtained from patients with ulcerative colitis (n = 4) and Crohn disease (n = 4). Normal tissue was obtained from uninvolved areas of extensive resections for carcinoma (n = 6). In all cases, specimens were obtained less than 5 min after removal to minimize influences associated with degradation artifacts and were processed for quantitative receptor autoradiography by using 125I-labeled Bolton-Hunter conjugates of NK, SK, and SP. In the normal colon a low concentration of SP receptor binding sites is expressed by submucosal arterioles and venules and a moderate concentration is expressed by the external circular muscle, whereas SK receptor binding sites are expressed in low concentrations by the external circular and longitudinal muscle. In contrast, specific NK binding sites were not observed in any area of the human colon. In colon tissue obtained from ulcerative colitis and Crohn disease patients, however, very high concentrations of SP receptor binding sites are expressed by arterioles and venules located in the submucosa, muscularis mucosa, external circular muscle, external longitudinal muscle, and serosa. In addition, very high concentrations of SP receptor binding sites are expressed within the germinal center of lymph nodules, whereas the concentrations of SP and SK binding sites expressed by the external muscle layers are not altered significantly. These results demonstrate that receptor binding sites for SP, but not SK or NK, are ectopically expressed in high concentrations (1000-2000 times normal) by cells involved in mediating inflammatory and immune responses. These data suggest that SP may be involved in the pathophysiology of inflammatory bowel disease and might provide some insight into the interaction between the nervous system and the regulation of inflammation and the immune response in human inflammatory disease.

Authors
Mantyh, CR; Gates, TS; Zimmerman, RP; Welton, ML; Passaro, EP; Vigna, SR; Maggio, JE; Kruger, L; Mantyh, PW
MLA Citation
Mantyh, CR, Gates, TS, Zimmerman, RP, Welton, ML, Passaro, EP, Vigna, SR, Maggio, JE, Kruger, L, and Mantyh, PW. "Receptor binding sites for substance P, but not substance K or neuromedin K, are expressed in high concentrations by arterioles, venules, and lymph nodules in surgical specimens obtained from patients with ulcerative colitis and Crohn disease." Proc Natl Acad Sci U S A 85.9 (May 1988): 3235-3239.
PMID
2834738
Source
pubmed
Published In
Proceedings of the National Academy of Sciences of USA
Volume
85
Issue
9
Publish Date
1988
Start Page
3235
End Page
3239

SUBSTANCE-P RECEPTORS ON CANINE CHIEF CELLS

Authors
VIGNA, SR; MANTYH, CR; MAGGIO, JE; SOLL, AH; MANTYH, PW
MLA Citation
VIGNA, SR, MANTYH, CR, MAGGIO, JE, SOLL, AH, and MANTYH, PW. "SUBSTANCE-P RECEPTORS ON CANINE CHIEF CELLS." May 1988.
Source
wos-lite
Published In
Gastroenterology
Volume
94
Issue
5
Publish Date
1988
Start Page
A480
End Page
A480

The localization of sensory nerve fibers and receptor binding sites for sensory neuropeptides in canine mesenteric lymph nodes.

Previous work has established that the central nervous system can modulate the immune response. Direct routes through which this regulation may occur are the sympathetic and sensory innervation of lymphoid organs. We investigated the innervation of canine mesenteric lymph nodes using immunohistochemistry and the expression of binding sites for sensory neuropeptides using quantitative receptor autoradiography. The sympathetic innervation of lymph nodes was examined by immunohistochemical methods using an antiserum directed against tyrosine hydroxylase (TOH), the rate limiting enzyme in catecholamine synthesis. TOH-containing fibers were associated with 90% of the blood vessels (arteries, veins, arterioles and venules) in the hilus, medullary and internodular regions of lymph nodes and in trabeculae with no obvious relationship to blood vessels. The sensory innervation of lymph nodes was investigated using antisera directed against the putative sensory neurotransmitters calcitonin gene-related peptide (CGRP) and substance P (SP). CGRP- and SP-containing fibers were detected in the hilus, the medullary region, and the internodular region of lymph nodes usually in association with arterioles and venules. About 50% of the arterioles and venules exhibited a CGRP innervation and a smaller fraction (5-10%) were innervated by SP-containing fibers. Few if any TOH, CGRP, and SP nerve fibers were detected in the germinal centers of lymph nodes. Using quantitative receptor autoradiography we studied the distribution of receptor binding sites for the sensory neuropeptides CGRP, SP, substance K (SK), vasoactive intestinal peptide (VIP), somatostatin (SOM), and bombesin. Specific CGRP binding sites were expressed throughout lymph nodes by trabeculae, arterioles, venules and 25% of the germinal centers. SP receptor binding sites were localized to arterioles and venules in the T cell regions and 25-30% of the germinal centers. VIP binding sites were localized to the internodular and T cell regions, to medullary cords, and to 10-20% of germinal centers. SK, SOM, and bombesin binding sites were not detected in the lymph nodes, although receptor binding sites for these peptides were detected with high specific/nonspecific binding ratios in other canine peripheral tissues. Taken together with previous results these findings suggest that the sympathetic and sensory innervation of mesenteric lymph nodes appears to be involved with the regulation of their blood and lymph flow. The neuropeptide receptor binding sites in lymph node germinal centers may be expressed by lymphocytes upon activation by antigens.(ABSTRACT TRUNCATED AT 400 WORDS)

Authors
Popper, P; Mantyh, CR; Vigna, SR; Maggio, JE; Mantyh, PW
MLA Citation
Popper, P, Mantyh, CR, Vigna, SR, Maggio, JE, and Mantyh, PW. "The localization of sensory nerve fibers and receptor binding sites for sensory neuropeptides in canine mesenteric lymph nodes." Peptides 9.2 (March 1988): 257-267.
PMID
2453853
Source
pubmed
Published In
Peptides
Volume
9
Issue
2
Publish Date
1988
Start Page
257
End Page
267

ALTERATIONS IN THE DENSITY OF RECEPTOR-BINDING SITES FOR SENSORY NEUROPEPTIDES IN THE SPINAL-CORD OF ARTHRITIC RATS

Authors
MANTYH, CR; GATES, T; ZIMMERMAN, RP; KRUGER, L; MAGGIO, JE; VIGNA, SR; BASBAUM, AI; LEVINE, J; MANTYH, PW
MLA Citation
MANTYH, CR, GATES, T, ZIMMERMAN, RP, KRUGER, L, MAGGIO, JE, VIGNA, SR, BASBAUM, AI, LEVINE, J, and MANTYH, PW. "ALTERATIONS IN THE DENSITY OF RECEPTOR-BINDING SITES FOR SENSORY NEUROPEPTIDES IN THE SPINAL-CORD OF ARTHRITIC RATS." 1988.
Source
wos-lite
Published In
ARTHRITIC RAT AS A MODEL OF CLINICAL PAIN
Volume
837
Publish Date
1988
Start Page
139
End Page
152

Localization of specific binding sites for bombesin in the canine gastrointestinal tract.

The goal of these studies was to determine the tissue and cell types possessing specific binding sites for bombesin/gastrin-releasing peptide in the canine gastrointestinal tract. Monoiodinated, biologically active (Tyr-4)-bombesin 14 (100 pM) was applied to sections of canine gut and localized using quantitative autoradiography. The highest density of bombesin/gastrin-releasing peptide specific binding sites occurred over endocrine cells in the antral mucosa. Specific binding sites were also found on the circular muscle layer of the gastric fundus, gastric antrum, and ileum, on longitudinal muscle of the gastric fundus and antrum, and on neuronal elements in the myenteric plexus in the gastric fundus, antrum, and small intestine. No evidence for specific binding of 125I-(Tyr-4)-bombesin 14 was found in sections of canine esophagus, gastric cardia, gallbladder, pancreas, or colon. These results suggest sites of direct action of bombesin and endogenous gastrin-releasing peptide for gastrin release and gastrointestinal motility.

Authors
Vigna, SR; Mantyh, CR; Giraud, AS; Soll, AH; Walsh, JH; Mantyh, PW
MLA Citation
Vigna, SR, Mantyh, CR, Giraud, AS, Soll, AH, Walsh, JH, and Mantyh, PW. "Localization of specific binding sites for bombesin in the canine gastrointestinal tract." Gastroenterology 93.6 (December 1987): 1287-1295.
PMID
3678747
Source
pubmed
Published In
Gastroenterology
Volume
93
Issue
6
Publish Date
1987
Start Page
1287
End Page
1295

LOCALIZATION OF BOMBESIN RECEPTORS IN HUMAN GASTROINTESTINAL-TRACT USING QUANTITATIVE RECEPTOR AUTORADIOGRAPHY

Authors
WELTON, ML; MANTYH, CR; GATES, TS; POPPER, P; VIGNA, SR; MAGGIO, JE; PASSARO, E; MANTYH, PW
MLA Citation
WELTON, ML, MANTYH, CR, GATES, TS, POPPER, P, VIGNA, SR, MAGGIO, JE, PASSARO, E, and MANTYH, PW. "LOCALIZATION OF BOMBESIN RECEPTORS IN HUMAN GASTROINTESTINAL-TRACT USING QUANTITATIVE RECEPTOR AUTORADIOGRAPHY." October 1987.
Source
wos-lite
Published In
Regulatory Peptides
Volume
19
Issue
1-2
Publish Date
1987
Start Page
144
End Page
144
DOI
10.1016/0167-0115(87)90165-0

LOCALIZATION OF SPECIFIC BINDING-SITES FOR BOMBESIN AND RELATED PEPTIDES IN THE GASTROINTESTINAL-TRACT

Authors
MANTYH, PW; MANTYH, CR; GIRAUD, AS; SOLL, AH; WALSH, JH; VIGNA, SR
MLA Citation
MANTYH, PW, MANTYH, CR, GIRAUD, AS, SOLL, AH, WALSH, JH, and VIGNA, SR. "LOCALIZATION OF SPECIFIC BINDING-SITES FOR BOMBESIN AND RELATED PEPTIDES IN THE GASTROINTESTINAL-TRACT." October 1987.
Source
wos-lite
Published In
Regulatory Peptides
Volume
19
Issue
1-2
Publish Date
1987
Start Page
125
End Page
125

Localization of specific binding sites for atrial natriuretic factor in the central nervous system of rat, guinea pig, cat and human.

Specific, high-affinity binding sites for atrial natriuretic factor (ANF) were identified and localized in the rat and guinea pig central nervous system (CNS), the cat brainstem, and the rat, guinea pig, cat and human spinal cord using quantitative autoradiographic techniques. The radioligands tested were rat 125I-ANF(1-28) in guinea pig, rat, cat and human tissues, human 125I-ANF in rat and human, and rat [3H]atriopeptin III in rat. All 3 radioligands labeled essentially the same structures in the brain and spinal cord of all species in which they were tested. In guinea pig very high concentrations of ANF binding sites were observed in the olfactory bulb, lateral olfactory tract and the granule cell layer of the cerebellum, high concentrations were observed in the fasciculus retroflexus, interpeduncular nucleus and subfornical organ. Moderate concentrations were observed in the nucleus accumbens, dorsomedial and suprachiasmatic hypothalamic nuclei, paraventricular thalamic nuclei, primary olfactory cortex and the subcommissural organ. High concentrations of ANF binding sites were also observed in the choroid plexus and the leptomeninges. Low concentrations were observed in the pineal gland. In the rat the same structures were labeled as in the guinea pig except that suprachiasmatic and dorsomedial hypothalamic nuclei, paraventricular thalamus and cerebellum were unlabeled. In the lower brainstem of the cat and all levels of the rat, guinea pig, cat and human spinal cord, the only site where specific binding was observed was in the pia/arachnoid. These findings suggest that ANF binding sites constitute several functional classes in the CNS as well as in a variety of other tissues. Outside the blood-brain barrier binding sites are prominent in glandular tissues implicated in the production of hormones involved in fluid and electrolyte balance, e.g. adrenal glomerulosa, neurohypophysis and subfornical organ, unstratified epithelia involved in ion gradient exchange, e.g. renal glomerulus, ciliary body, choroid plexus and pia mater; crossing the blood-brain barrier are sites in the anterior hypothalamus, e.g. organum vasculosum, regions of the brain parenchyma associated with angiotensin II binding sites, e.g. dorsomedial nucleus of hypothalamus, some of which may be occupied by brain rather than cardiac synthesized ANF, regions of brain lacking an obvious role in fluid and ion exchange or regulation, e.g. cerebellum, although association with K+,Na+-ATPase in guinea pig cerebellum may be a relevant clue and brain regions possibly implicated in an integrative and/or indirect regulatory role in fluid and electrolyte balance.(ABSTRACT TRUNCATED AT 400 WORDS)

Authors
Mantyh, CR; Kruger, L; Brecha, NC; Mantyh, PW
MLA Citation
Mantyh, CR, Kruger, L, Brecha, NC, and Mantyh, PW. "Localization of specific binding sites for atrial natriuretic factor in the central nervous system of rat, guinea pig, cat and human." Brain Res 412.2 (June 2, 1987): 329-342. (Review)
PMID
2955851
Source
pubmed
Published In
Brain Research
Volume
412
Issue
2
Publish Date
1987
Start Page
329
End Page
342

Estrous cyclicity of 125I-cholecystokinin octapeptide binding in the ventromedial hypothalamic nucleus. Evidence for downmodulation by estrogen.

Although there is a good correlation between the levels of gonadal steroids and sex differences in reproductive behavior and food intake, the neurochemical mechanisms by which a gonadal steroid may regulate these behaviors remain unknown. An important central nervous site for steroid modulation of food intake and reproduction is the ventromedial nucleus of the hypothalamus (VMH). Recently it has been suggested that some of the activities of the VMH are dependent on the neuroactive peptide cholecystokinin octapeptide (CCK). High levels of CCK in the VMH have been measured by radioimmunoassay, and immunohistochemical analysis has revealed a dense plexus of CCK fibers and terminals which appose and make synaptic contact with VMH neurons. There is, however, a paucity of information concerning the presence of CCK-binding sites in the VMH. This study demonstrates high levels of 125I-CCK8 binding in the VMH of male and female rats. Tissue sampled on the morning of estrus revealed depressed levels of CCK binding, and, while ovariectomy itself did not affect binding, ovariectomy followed by estrogen replacement depressed CCK binding. These results provide evidence for an estrogenic effect on CCK-binding sites that may help elucidate a role of CCK in the VMH.

Authors
Akesson, TR; Mantyh, PW; Mantyh, CR; Matt, DW; Micevych, PE
MLA Citation
Akesson, TR, Mantyh, PW, Mantyh, CR, Matt, DW, and Micevych, PE. "Estrous cyclicity of 125I-cholecystokinin octapeptide binding in the ventromedial hypothalamic nucleus. Evidence for downmodulation by estrogen." Neuroendocrinology 45.4 (April 1987): 257-262.
PMID
3574604
Source
pubmed
Published In
Neuroendocrinology
Volume
45
Issue
4
Publish Date
1987
Start Page
257
End Page
262

USE OF THE RENAL BIOPSY TO PROBE THE PATHOPHYSIOLOGY OF HUMAN RENAL-DISEASE - GLOMERULAR BINDING OF ATRIAL-NATRIURETIC-PEPTIDE (ANP)

Authors
FINE, LG; MANTYH, CR; COHEN, A; MANTYH, PW
MLA Citation
FINE, LG, MANTYH, CR, COHEN, A, and MANTYH, PW. "USE OF THE RENAL BIOPSY TO PROBE THE PATHOPHYSIOLOGY OF HUMAN RENAL-DISEASE - GLOMERULAR BINDING OF ATRIAL-NATRIURETIC-PEPTIDE (ANP)." January 1987.
Source
wos-lite
Published In
Kidney international
Volume
31
Issue
1
Publish Date
1987
Start Page
198
End Page
198

Localization of specific binding sites for atrial natriuretic factor in peripheral tissues of the guinea pig, rat, and human.

Specific, high affinity atrial natriuretic factor (ANF) binding sites were identified and localized by autoradiographic techniques in peripheral tissues of the guinea pig, rat, and human. In the guinea pig kidney, high concentrations of ANF binding sites were located in the glomerular apparatus, outer medulla, and small renal arteries. Other peripheral tissues containing ANF binding sites included the zona glomerulosa of the adrenal cortex, the smooth muscle layer of the aorta and gallbladder, the lung parenchyma, the posterior lobe of the pituitary, the ciliary body of the eye, and the leptomeninges and choroid plexus of the brain. The distribution of ANF binding sites in the rat and human kidney was nearly identical to those seen in the guinea pig kidney; high concentrations were present in the glomerular apparatus, outer medulla, and small renal arteries. These results are consistent with earlier physiological and pharmacological studies that suggested that ANF plays a functional role in the regulation of extracellular fluid volume and blood pressure. There appears to be little species variation in the location and concentration of renal ANF binding sites, suggesting that, at least in the kidney, the results in experimental animals are relevant to the actions of ANF in humans. The finding that ANF binding sites were stable and present in high concentrations in human postmortem kidneys further suggests that these tissues may be amenable to testing for the involvement of ANF receptor dysfunction in diseases such as hypertension and congestive heart failure.

Authors
Mantyh, CR; Kruger, L; Brecha, NC; Mantyh, PW
MLA Citation
Mantyh, CR, Kruger, L, Brecha, NC, and Mantyh, PW. "Localization of specific binding sites for atrial natriuretic factor in peripheral tissues of the guinea pig, rat, and human." Hypertension 8.8 (August 1986): 712-721.
PMID
2942474
Source
pubmed
Published In
Hypertension
Volume
8
Issue
8
Publish Date
1986
Start Page
712
End Page
721

NEUROPEPTIDES AND THEIR RECEPTORS IN HUMAN SPINAL-CORD AND DORSAL-ROOT GANGLION NEURONS

Authors
ABOLS, IA; MANTYH, CR; MANTYH, PW
MLA Citation
ABOLS, IA, MANTYH, CR, and MANTYH, PW. "NEUROPEPTIDES AND THEIR RECEPTORS IN HUMAN SPINAL-CORD AND DORSAL-ROOT GANGLION NEURONS." April 1986.
Source
wos-lite
Published In
Neurology
Volume
36
Issue
4
Publish Date
1986
Start Page
260
End Page
260

Differential localization of cholecystokinin-8 binding sites in the rat vs. the guinea pig brain.

Authors
Mantyh, CR; Mantyh, PW
MLA Citation
Mantyh, CR, and Mantyh, PW. "Differential localization of cholecystokinin-8 binding sites in the rat vs. the guinea pig brain." Eur J Pharmacol 113.1 (July 11, 1985): 137-139.
PMID
2995055
Source
pubmed
Published In
European Journal of Pharmacology
Volume
113
Issue
1
Publish Date
1985
Start Page
137
End Page
139

Specific binding sites for atrial natriuretic factor in the human kidney.

Authors
Mantyh, CR; Brecha, NC; Soon-Shiong, P; Mantyh, PW
MLA Citation
Mantyh, CR, Brecha, NC, Soon-Shiong, P, and Mantyh, PW. "Specific binding sites for atrial natriuretic factor in the human kidney." N Engl J Med 312.26 (June 27, 1985): 1710-. (Letter)
PMID
3158816
Source
pubmed
Published In
The New England journal of medicine
Volume
312
Issue
26
Publish Date
1985
Start Page
1710
DOI
10.1056/NEJM198506273122617

Flap repair of complex pilonidal sinus: a single institution experience

Authors
Kokosis, G; Barbas, A; Ong, C; Levinson, H; Erdmann, D; Mantyh, CR
MLA Citation
Kokosis, G, Barbas, A, Ong, C, Levinson, H, Erdmann, D, and Mantyh, CR. "Flap repair of complex pilonidal sinus: a single institution experience (Published online)." European Journal of Plastic Surgery.
Source
crossref
Published In
European Journal of Plastic Surgery
DOI
10.1007/s00238-017-1361-4
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