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Garman, Katherine Schuver

Overview:

My research focuses on injury, repair, and cancer development in the gastrointestinal tract. My laboratory performs translational research with the goal of improving health of the gastrointestinal tract. Our work is based in observations from human clinical research. We use databases of esophageal and colon disease to learn more about clinical risk factors for disease. We also use pathology samples of tumors to study the gastrointestinal tract in different states: healthy, inflamed or damaged, and with cancer.

Positions:

Assistant Professor of Medicine

Medicine, Gastroenterology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Affiliate of the Regeneration Next Initiative

Regeneration Next Initiative
School of Medicine

Education:

M.D. 2002

M.D. — Duke University

Medical Resident, Medicine

Duke University

Fellow In Gastroenterology, Medicine

Duke University

Chief Resident, Medicine

Duke University School of Medicine

Fellow In Gastroenterology, Medicine

Duke University

Grants:

Postdoctoral training in genomic medicine research

Administered By
Duke Center for Applied Genomics and Precision Medicine
AwardedBy
National Institutes of Health
Role
Co-Mentor
Start Date
June 14, 2017
End Date
May 31, 2022

Duke Training Grant in Digestive Diseases and Nutrition

Administered By
Medicine, Gastroenterology
AwardedBy
National Institutes of Health
Role
Mentor
Start Date
July 01, 1988
End Date
June 30, 2021

Nanoplasmonics-based molecular analysis tool for molecular biomarkers of cancer

Administered By
Biomedical Engineering
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
September 08, 2015
End Date
July 31, 2018

Submucosal esophageal structures as a progenitor niche for esophageal repair

Administered By
Medicine, Gastroenterology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
April 01, 2013
End Date
March 31, 2018

Epigenetic Control of Intestinal Inflammation

Administered By
Cell Biology
AwardedBy
Kenneth Rainin Foundation
Role
Collaborator
Start Date
October 01, 2016
End Date
December 31, 2017

Epigenetic control of intestinal inflammation

Administered By
Cell Biology
AwardedBy
Kenneth Rainin Foundation
Role
Collaborator
Start Date
October 01, 2015
End Date
September 30, 2016

Development of a Porcine Model of Esophageal Injury and Repair

Administered By
Medicine, Gastroenterology
AwardedBy
University of North Carolina - Chapel Hill
Role
Principal Investigator
Start Date
December 01, 2012
End Date
November 30, 2014
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Publications:

Porcine Esophageal Submucosal Gland Culture Model Shows Capacity for Proliferation and Differentiation.

Although cells comprising esophageal submucosal glands (ESMGs) represent a potential progenitor cell niche, new models are needed to understand their capacity to proliferate and differentiate. By histologic appearance, ESMGs have been associated with both overlying normal squamous epithelium and columnar epithelium. Our aim was to assess ESMG proliferation and differentiation in a 3-dimensional culture model.We evaluated proliferation in human ESMGs from normal and diseased tissue by proliferating cell nuclear antigen immunohistochemistry. Next, we compared 5-ethynyl-2'-deoxyuridine labeling in porcine ESMGs in vivo before and after esophageal injury with a novel in vitro porcine organoid ESMG model. Microarray analysis of ESMGs in culture was compared with squamous epithelium and fresh ESMGs.Marked proliferation was observed in human ESMGs of diseased tissue. This activated ESMG state was recapitulated after esophageal injury in an in vivo porcine model, ESMGs assumed a ductal appearance with increased proliferation compared with control. Isolated and cultured porcine ESMGs produced buds with actively cycling cells and passaged to form epidermal growth factor-dependent spheroids. These spheroids were highly proliferative and were passaged multiple times. Two phenotypes of spheroids were identified: solid squamous (P63+) and hollow/ductal (cytokeratin 7+). Microarray analysis showed spheroids to be distinct from parent ESMGs and enriched for columnar transcripts.Our results suggest that the activated ESMG state, seen in both human disease and our porcine model, may provide a source of cells to repopulate damaged epithelium in a normal manner (squamous) or abnormally (columnar epithelium). This culture model will allow the evaluation of factors that drive ESMGs in the regeneration of injured epithelium. The raw microarray data have been uploaded to the National Center for Biotechnology Information Gene Expression Omnibus (accession number: GSE100543).

Authors
von Furstenberg, RJ; Li, J; Stolarchuk, C; Feder, R; Campbell, A; Kruger, L; Gonzalez, LM; Blikslager, AT; Cardona, DM; McCall, SJ; Henning, SJ; Garman, KS
MLA Citation
von Furstenberg, RJ, Li, J, Stolarchuk, C, Feder, R, Campbell, A, Kruger, L, Gonzalez, LM, Blikslager, AT, Cardona, DM, McCall, SJ, Henning, SJ, and Garman, KS. "Porcine Esophageal Submucosal Gland Culture Model Shows Capacity for Proliferation and Differentiation." Cellular and molecular gastroenterology and hepatology 4.3 (November 2017): 385-404.
PMID
28936470
Source
epmc
Published In
Cellular and molecular gastroenterology and hepatology
Volume
4
Issue
3
Publish Date
2017
Start Page
385
End Page
404
DOI
10.1016/j.jcmgh.2017.07.005

Ductular and proliferative response of esophageal submucosal glands in a porcine model of esophageal injury and repair.

Esophageal injury is a risk factor for diseases such as Barrett's esophagus (BE) and esophageal adenocarcinoma. To improve understanding of signaling pathways associated with both normal and abnormal repair, animal models are needed. Traditional rodent models of esophageal repair are limited by the absence of esophageal submucosal glands (ESMGs), which are present in the human esophagus. Previously, we identified acinar ductal metaplasia in human ESMGs in association with both esophageal injury and cancer. In addition, the SOX9 transcription factor has been associated with generation of columnar epithelium and the pathogenesis of BE and is present in ESMGs. To test our hypothesis that ESMGs activate after esophageal injury with an increase in proliferation, generation of a ductal phenotype, and expression of SOX9, we developed a porcine model of esophageal injury and repair using radiofrequency ablation (RFA). The porcine esophagus contains ESMGs, and RFA produces a consistent and reproducible mucosal injury in the esophagus. Here we present a temporal assessment of this model of esophageal repair. Porcine esophagus was evaluated at 0, 6, 18, 24, 48, and 72 h and 5 and 7 days following RFA and compared with control uninjured esophagus. Following RFA, ESMGs demonstrated an increase in ductal phenotype, echoing our prior studies in humans. Proliferation increased in both squamous epithelium and ESMGs postinjury with a prominent population of SOX9-positive cells in ESMGs postinjury. This model promises to be useful in future experiments evaluating mechanisms of esophageal repair.NEW & NOTEWORTHY A novel porcine model of injury and repair using radiofrequency ablation has been developed, allowing for reproducible injury to the esophagus to study repair in an animal model with esophageal submucosal glands, a key anatomical feature and missing in rodent models but possibly harboring progenitor cells. There is a strong translational component to this porcine model given the anatomical and physiological similarities between pigs and humans.

Authors
Krüger, L; Gonzalez, LM; Pridgen, TA; McCall, SJ; von Furstenberg, RJ; Harnden, I; Carnighan, GE; Cox, AM; Blikslager, AT; Garman, KS
MLA Citation
Krüger, L, Gonzalez, LM, Pridgen, TA, McCall, SJ, von Furstenberg, RJ, Harnden, I, Carnighan, GE, Cox, AM, Blikslager, AT, and Garman, KS. "Ductular and proliferative response of esophageal submucosal glands in a porcine model of esophageal injury and repair." American journal of physiology. Gastrointestinal and liver physiology 313.3 (September 2017): G180-G191.
PMID
28572084
Source
epmc
Published In
American journal of physiology. Gastrointestinal and liver physiology
Volume
313
Issue
3
Publish Date
2017
Start Page
G180
End Page
G191
DOI
10.1152/ajpgi.00036.2017

Origin of Barrett's Epithelium: Esophageal Submucosal Glands.

The origin of the progenitor cell for Barrett's esophagus remains a major unsolved mystery. Understanding the source of this progenitor may improve strategies to prevent the development of esophageal adenocarcinoma. Esophageal submucosal glands (ESMGs) and ducts may serve as a potential source of progenitor cells that respond to esophageal injury. Through the use of human histologic and molecular analysis, ESMGs and ducts have been described in physical continuity with areas of columnar esophagus, and shared mutations have been described between ESMG ducts and Barrett's esophagus. Acinar ductal metaplasia, associated with carcinogenesis in other organs, occurs within ESMGs with human esophageal injury and esophageal adenocarcinoma. By using atypical animal models, a squamous epithelial defect well above the gastroesophageal junction healed to columnar epithelium and continuity of ESMG ducts was noted in the new epithelium. Increased proliferation in ESMGs and ducts in response to injury also has been noted in human beings and animals.

Authors
Garman, KS
MLA Citation
Garman, KS. "Origin of Barrett's Epithelium: Esophageal Submucosal Glands." Cellular and molecular gastroenterology and hepatology 4.1 (July 2017): 153-156.
PMID
28593186
Source
epmc
Published In
Cellular and molecular gastroenterology and hepatology
Volume
4
Issue
1
Publish Date
2017
Start Page
153
End Page
156
DOI
10.1016/j.jcmgh.2017.01.016

Integrated genomic characterization of oesophageal carcinoma.

Oesophageal cancers are prominent worldwide; however, there are few targeted therapies and survival rates for these cancers remain dismal. Here we performed a comprehensive molecular analysis of 164 carcinomas of the oesophagus derived from Western and Eastern populations. Beyond known histopathological and epidemiologic distinctions, molecular features differentiated oesophageal squamous cell carcinomas from oesophageal adenocarcinomas. Oesophageal squamous cell carcinomas resembled squamous carcinomas of other organs more than they did oesophageal adenocarcinomas. Our analyses identified three molecular subclasses of oesophageal squamous cell carcinomas, but none showed evidence for an aetiological role of human papillomavirus. Squamous cell carcinomas showed frequent genomic amplifications of CCND1 and SOX2 and/or TP63, whereas ERBB2, VEGFA and GATA4 and GATA6 were more commonly amplified in adenocarcinomas. Oesophageal adenocarcinomas strongly resembled the chromosomally unstable variant of gastric adenocarcinoma, suggesting that these cancers could be considered a single disease entity. However, some molecular features, including DNA hypermethylation, occurred disproportionally in oesophageal adenocarcinomas. These data provide a framework to facilitate more rational categorization of these tumours and a foundation for new therapies.

Authors
Cancer Genome Atlas Research Network, ; Analysis Working Group: Asan University, ; BC Cancer Agency, ; Brigham and Women’s Hospital, ; Broad Institute, ; Brown University, ; Case Western Reserve University, ; Dana-Farber Cancer Institute, ; Duke University, ; Greater Poland Cancer Centre, ; Harvard Medical School, ; Institute for Systems Biology, ; KU Leuven, ; Mayo Clinic, ; Memorial Sloan Kettering Cancer Center, ; National Cancer Institute, ; Nationwide Children’s Hospital, et al.
MLA Citation
Cancer Genome Atlas Research Network, , Analysis Working Group: Asan University, , BC Cancer Agency, , Brigham and Women’s Hospital, , Broad Institute, , Brown University, , Case Western Reserve University, , Dana-Farber Cancer Institute, , Duke University, , Greater Poland Cancer Centre, , Harvard Medical School, , Institute for Systems Biology, , KU Leuven, , Mayo Clinic, , Memorial Sloan Kettering Cancer Center, , National Cancer Institute, , and Nationwide Children’s Hospital, et al. "Integrated genomic characterization of oesophageal carcinoma." Nature 541.7636 (January 4, 2017): 169-175.
PMID
28052061
Source
epmc
Published In
Nature
Volume
541
Issue
7636
Publish Date
2017
Start Page
169
End Page
175
DOI
10.1038/nature20805

Ductal metaplasia in oesophageal submucosal glands is associated with inflammation and oesophageal adenocarcinoma.

Recent studies have suggested that oesophageal submucosal gland (ESMG) ducts harbour progenitor cells that may contribute to oesophageal metaplasia. Our objective was to determine whether histological differences exist between the ESMGs of individuals with and without oesophageal adenocarcinoma (EAC).We performed histological assessment of 343 unique ESMGs from 30 control patients, 24 patients with treatment-naïve high-grade columnar dysplasia (HGD) or EAC, and 23 non-EAC oesophagectomy cases. A gastrointestinal pathologist assessed haematoxylin and eosin-stained ESMG images by using a scoring system that assigns individual ESMG acini to five histological types (mucous, serous, oncocytic, dilated, or ductal metaplastic). In our model, ductal metaplastic acini were more common in patients with HGD/EAC (12.7%) than in controls (3.5%) (P = 0.006). We also identified greater proportions of acini with dilation (21.9%, P < 0.001) and, to a lesser extent, ductal metaplasia (4.3%, P = 0.001) in non-EAC oesophagectomy cases than in controls. Ductal metaplasia tended to occur in areas of mucosal ulceration or tumour.We found a clear association between ductal metaplastic ESMG acini and HGD/EAC. Non-EAC cases had dilated acini and some ductal dilation. Because ESMGs and ducts harbour putative progenitor cells, these associations could have significance for understanding the pathogenesis of EAC.

Authors
Garman, KS; Kruger, L; Thomas, S; Swiderska-Syn, M; Moser, BK; Diehl, AM; McCall, SJ
MLA Citation
Garman, KS, Kruger, L, Thomas, S, Swiderska-Syn, M, Moser, BK, Diehl, AM, and McCall, SJ. "Ductal metaplasia in oesophageal submucosal glands is associated with inflammation and oesophageal adenocarcinoma." Histopathology 67.6 (December 2015): 771-782.
PMID
25847432
Source
epmc
Published In
Histopathology
Volume
67
Issue
6
Publish Date
2015
Start Page
771
End Page
782
DOI
10.1111/his.12707

Comprehensive molecular characterization of gastric adenocarcinoma.

Gastric cancer is a leading cause of cancer deaths, but analysis of its molecular and clinical characteristics has been complicated by histological and aetiological heterogeneity. Here we describe a comprehensive molecular evaluation of 295 primary gastric adenocarcinomas as part of The Cancer Genome Atlas (TCGA) project. We propose a molecular classification dividing gastric cancer into four subtypes: tumours positive for Epstein-Barr virus, which display recurrent PIK3CA mutations, extreme DNA hypermethylation, and amplification of JAK2, CD274 (also known as PD-L1) and PDCD1LG2 (also known as PD-L2); microsatellite unstable tumours, which show elevated mutation rates, including mutations of genes encoding targetable oncogenic signalling proteins; genomically stable tumours, which are enriched for the diffuse histological variant and mutations of RHOA or fusions involving RHO-family GTPase-activating proteins; and tumours with chromosomal instability, which show marked aneuploidy and focal amplification of receptor tyrosine kinases. Identification of these subtypes provides a roadmap for patient stratification and trials of targeted therapies.

Authors
Cancer Genome Atlas Research Network,
MLA Citation
Cancer Genome Atlas Research Network, . "Comprehensive molecular characterization of gastric adenocarcinoma." Nature 513.7517 (September 2014): 202-209.
PMID
25079317
Source
epmc
Published In
Nature
Volume
513
Issue
7517
Publish Date
2014
Start Page
202
End Page
209
DOI
10.1038/nature13480

Delayed Specimen Collection May Artifactually Damage the Mucosal Surface in Barrett's EMR Specimens

Authors
Zhang, X; Zhao, L; Guy, CD; McCall, SJ; Cardona, DM; Burbridge, RA; Garman, KS; Branch, MS; Siddiqui, U; Xiao, S-Y; Waxman, I; Hart, J
MLA Citation
Zhang, X, Zhao, L, Guy, CD, McCall, SJ, Cardona, DM, Burbridge, RA, Garman, KS, Branch, MS, Siddiqui, U, Xiao, S-Y, Waxman, I, and Hart, J. "Delayed Specimen Collection May Artifactually Damage the Mucosal Surface in Barrett's EMR Specimens." February 2014.
Source
wos-lite
Published In
Laboratory Investigation
Volume
94
Publish Date
2014
Start Page
211A
End Page
211A

TWEAK/Fn14 signaling is required for liver regeneration after partial hepatectomy in mice.

BACKGROUND & AIMS: Pro-inflammatory cytokines are important for liver regeneration after partial hepatectomy (PH). Expression of Fibroblast growth factor-inducible 14 (Fn14), the receptor for TNF-like weak inducer of apoptosis (TWEAK), is induced rapidly after PH and remains elevated throughout the period of peak hepatocyte replication. The role of Fn14 in post-PH liver regeneration is uncertain because Fn14 is expressed by liver progenitors and TWEAK-Fn14 interactions stimulate progenitor growth, but replication of mature hepatocytes is thought to drive liver regeneration after PH. METHODS: To clarify the role of TWEAK-Fn14 after PH, we compared post-PH regenerative responses in wild type (WT) mice, Fn14 knockout (KO) mice, TWEAK KO mice, and WT mice treated with anti-TWEAK antibodies. RESULTS: In WT mice, rare Fn14(+) cells localized with other progenitor markers in peri-portal areas before PH. PH rapidly increased proliferation of Fn14(+) cells; hepatocytic cells that expressed Fn14 and other progenitor markers, such as Lgr5, progressively accumulated from 12-8 h post-PH and then declined to baseline by 96 h. When TWEAK/Fn14 signaling was disrupted, progenitor accumulation, induction of pro-regenerative cytokines, hepatocyte and cholangiocyte proliferation, and over-all survival were inhibited, while post-PH liver damage and bilirubin levels were increased. TWEAK stimulated proliferation and increased Lgr5 expression in cultured liver progenitors, but had no effect on either parameter in cultured primary hepatocytes. CONCLUSIONS: TWEAK-FN14 signaling is necessary for the healthy adult liver to regenerate normally after acute partial hepatectomy.

Authors
Karaca, G; Swiderska-Syn, M; Xie, G; Syn, W-K; Krüger, L; Machado, MV; Garman, K; Choi, SS; Michelotti, GA; Burkly, LC; Ochoa, B; Diehl, AM
MLA Citation
Karaca, G, Swiderska-Syn, M, Xie, G, Syn, W-K, Krüger, L, Machado, MV, Garman, K, Choi, SS, Michelotti, GA, Burkly, LC, Ochoa, B, and Diehl, AM. "TWEAK/Fn14 signaling is required for liver regeneration after partial hepatectomy in mice. (Published online)" PLoS One 9.1 (2014): e83987-.
Website
http://hdl.handle.net/10161/11083
PMID
24416188
Source
pubmed
Published In
PloS one
Volume
9
Issue
1
Publish Date
2014
Start Page
e83987
DOI
10.1371/journal.pone.0083987

MicroRNA expression differentiates squamous epithelium from barrett's esophagus and esophageal cancer

Background: Current strategies fail to identify most patients with esophageal adenocarcinoma (EAC) before the disease becomes advanced and incurable. Given the dismal prognosis associated with EAC, improvements in detection of early-stage esophageal neoplasia are needed. Aim: We sought to assess whether differential expression of microRNAs could discriminate between squamous epithelium, Barrett's esophagus (BE), and EAC. Methods: We analyzed microRNA expression in a discovery cohort of human endoscopic biopsy samples from 36 patients representing normal squamous esophagus (n = 11), BE (n = 14), and high-grade dysplasia/EAC (n = 11). RNA was assessed using microarrays representing 847 human microRNAs followed by quantitative real-time polymerase chain reaction (qRT-PCR) verification of nine microRNAs. In a second cohort (n = 18), qRT-PCR validation of five miRNAs was performed. Expression of 59 microRNAs associated with BE/EAC in the literature was assessed in our training cohort. Known esophageal cell lines were used to compare miRNA expression to tissue miRNAs. Results: After controlling for multiple comparisons, we found 34 miRNAs differentially expressed between squamous esophagus and BE/EAC by microarray analysis. However, miRNA expression did not reliably differentiate non-dysplastic BE from EAC. In the validation cohort, all five microRNAs selected for qRT-PCR validation differentiated between squamous samples and BE/EAC. Microarray results supported 14 of the previously reported microRNAs associated with BE/EAC in the literature. Cell lines did not generally reflect miRNA expression found in vivo. Conclusions: These data indicate that miRNAs differ between squamous esophageal epithelium and BE/EAC, but do not distinguish between BE and EAC. We suggest prospective evaluation of miRNAs in patients at high risk for EAC. © 2013 Springer Science+Business Media New York.

Authors
Garman, KS; Owzar, K; Hauser, ER; Westfall, K; Anderson, BR; Souza, RF; Diehl, AM; Provenzale, D; Shaheen, NJ
MLA Citation
Garman, KS, Owzar, K, Hauser, ER, Westfall, K, Anderson, BR, Souza, RF, Diehl, AM, Provenzale, D, and Shaheen, NJ. "MicroRNA expression differentiates squamous epithelium from barrett's esophagus and esophageal cancer." Digestive Diseases and Sciences 58.11 (November 1, 2013): 3178-3188.
Source
scopus
Published In
Digestive Diseases and Sciences
Volume
58
Issue
11
Publish Date
2013
Start Page
3178
End Page
3188
DOI
10.1007/s10620-013-2806-7

MicroRNA expression differentiates squamous epithelium from Barrett's esophagus and esophageal cancer.

BACKGROUND: Current strategies fail to identify most patients with esophageal adenocarcinoma (EAC) before the disease becomes advanced and incurable. Given the dismal prognosis associated with EAC, improvements in detection of early-stage esophageal neoplasia are needed. AIM: We sought to assess whether differential expression of microRNAs could discriminate between squamous epithelium, Barrett's esophagus (BE), and EAC. METHODS: We analyzed microRNA expression in a discovery cohort of human endoscopic biopsy samples from 36 patients representing normal squamous esophagus (n = 11), BE (n = 14), and high-grade dysplasia/EAC (n = 11). RNA was assessed using microarrays representing 847 human microRNAs followed by quantitative real-time polymerase chain reaction (qRT-PCR) verification of nine microRNAs. In a second cohort (n = 18), qRT-PCR validation of five miRNAs was performed. Expression of 59 microRNAs associated with BE/EAC in the literature was assessed in our training cohort. Known esophageal cell lines were used to compare miRNA expression to tissue miRNAs. RESULTS: After controlling for multiple comparisons, we found 34 miRNAs differentially expressed between squamous esophagus and BE/EAC by microarray analysis. However, miRNA expression did not reliably differentiate non-dysplastic BE from EAC. In the validation cohort, all five microRNAs selected for qRT-PCR validation differentiated between squamous samples and BE/EAC. Microarray results supported 14 of the previously reported microRNAs associated with BE/EAC in the literature. Cell lines did not generally reflect miRNA expression found in vivo. CONCLUSIONS: These data indicate that miRNAs differ between squamous esophageal epithelium and BE/EAC, but do not distinguish between BE and EAC. We suggest prospective evaluation of miRNAs in patients at high risk for EAC.

Authors
Garman, KS; Owzar, K; Hauser, ER; Westfall, K; Anderson, BR; Souza, RF; Diehl, AM; Provenzale, D; Shaheen, NJ
MLA Citation
Garman, KS, Owzar, K, Hauser, ER, Westfall, K, Anderson, BR, Souza, RF, Diehl, AM, Provenzale, D, and Shaheen, NJ. "MicroRNA expression differentiates squamous epithelium from Barrett's esophagus and esophageal cancer." Dig Dis Sci 58.11 (November 2013): 3178-3188.
PMID
23925817
Source
pubmed
Published In
Digestive Diseases and Sciences
Volume
58
Issue
11
Publish Date
2013
Start Page
3178
End Page
3188
DOI
10.1007/s10620-013-2806-7

The Role of Pleiotrophin Signaling in the Hepatic Stem Cell Niche

Authors
Tucker, A; Michelotti, GA; Choi, SS; Xie, G; Karaca, G; Swiderska-Syn, M; Kruger, L; Machado, MV; Garman, KS; Diehl, AM
MLA Citation
Tucker, A, Michelotti, GA, Choi, SS, Xie, G, Karaca, G, Swiderska-Syn, M, Kruger, L, Machado, MV, Garman, KS, and Diehl, AM. "The Role of Pleiotrophin Signaling in the Hepatic Stem Cell Niche." October 2013.
Source
wos-lite
Published In
Hepatology
Volume
58
Publish Date
2013
Start Page
1007A
End Page
1007A

Cellular origins and molecular mechanisms of Barrett's esophagus and esophageal adenocarcinoma.

This paper presents commentaries on animal models used for Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) research; acid- and bile-induced chromosomal instability and clonal selection during the progression of BE to EAC; how the components of gastric refluxate, especially acid and bile salts, promote carcinogenesis in metaplastic BE; genome-wide changes in DNA methylation and transcription involved in BE carcinogenesis; the potential role of miRNA in the development of BE and EAC; the effect of inflammatory cytokines linked to obesity on the activation of cell-death pathways and cell survival in BE and esophageal cancer; and the role of autophagy in esophageal cancer development.

Authors
Fang, Y; Chen, X; Bajpai, M; Verma, A; Das, KM; Souza, RF; Garman, KS; Donohoe, CL; O'Farrell, NJ; Reynolds, JV; Dvorak, K
MLA Citation
Fang, Y, Chen, X, Bajpai, M, Verma, A, Das, KM, Souza, RF, Garman, KS, Donohoe, CL, O'Farrell, NJ, Reynolds, JV, and Dvorak, K. "Cellular origins and molecular mechanisms of Barrett's esophagus and esophageal adenocarcinoma." Ann N Y Acad Sci 1300 (October 2013): 187-199. (Review)
PMID
24117642
Source
pubmed
Published In
Annals of the New York Academy of Sciences
Volume
1300
Publish Date
2013
Start Page
187
End Page
199
DOI
10.1111/nyas.12249

Feasibility, safety, acceptability, and yield of office-based, screening transnasal esophagoscopy (with video)

Background: Endoscopic screening for esophageal neoplasia can identify patients eligible for early intervention for precancerous lesions. Unsedated transnasal esophagoscopy may provide an efficient and accurate endoscopic assessment with fewer risks and less cost, compared with conventional upper endoscopy. Objective: To assess the feasibility, safety, acceptability, and yield of unsedated transnasal esophagoscopy in a primary care population. Design: Multicenter, prospective, cross-sectional study. Setting: Two outpatient tertiary-care centers. Patients: This study involved a general medical clinic population aged between 40 and 85 years. Intervention: Unsedated, office-based transnasal esophagoscopy. Main Outcome Measurements: Procedure yield; completeness of examination; procedure length; adverse events and complications; choking, gagging, pain, or anxiety during the examination; and overall tolerability. Results: A total of 426 participants (mean [± standard deviation] age 55.8 ± 9.5 years; 43% male) enrolled in the study, and 422 (99%) completed the examination. Mean (± standard deviation) examination time was 3.7 ± 1.8 minutes. There were no serious adverse events, and 12 participants (2.8%) reported minor complications. Participants reported minimal choking, gagging, pain, or anxiety. The examination was well-tolerated by most participants. Overall, 38% of participants had an esophageal finding that changed management (34% erosive esophagitis, 4% Barrett's esophagus). Limitations: Nonrandomized study, tertiary-care centers only, self-selected population with a large proportion reporting esophageal symptoms. Conclusion: Unsedated transnasal esophagoscopy is a feasible, safe, and well-tolerated method to screen for esophageal disease in a primary care population. Endoscopic findings are common in this patient population. © 2012 American Society for Gastrointestinal Endoscopy.

Authors
Peery, AF; Hoppo, T; Garman, KS; Dellon, ES; Daugherty, N; Bream, S; Sanz, AF; Davison, J; Spacek, M; Connors, D; Faulx, AL; Chak, A; Luketich, JD; Shaheen, NJ; Jobe, BA
MLA Citation
Peery, AF, Hoppo, T, Garman, KS, Dellon, ES, Daugherty, N, Bream, S, Sanz, AF, Davison, J, Spacek, M, Connors, D, Faulx, AL, Chak, A, Luketich, JD, Shaheen, NJ, and Jobe, BA. "Feasibility, safety, acceptability, and yield of office-based, screening transnasal esophagoscopy (with video)." Gastrointestinal Endoscopy 75.5 (2012): 945-953.e2.
PMID
22425272
Source
scival
Published In
Gastrointestinal Endoscopy
Volume
75
Issue
5
Publish Date
2012
Start Page
945
End Page
953.e2
DOI
10.1016/j.gie.2012.01.021

Ablative therapies for Barrett's esophagus.

Barrett's esophagus has gained increased clinical attention because of its association with esophageal adenocarcinoma, a cancer with increasing incidence and poor survival rates. The goals of ablating Barrett's esophagus are to decrease esophageal cancer rates and to improve overall survival and quality of life. Different techniques have been developed and tested for their effectiveness eradicating Barrett's epithelium. This review assesses the literature associated with different ablative techniques. The safety and efficacy of different techniques are discussed. This review concludes with recommendations for the clinician, including specific strategies for patient care decisions for patients with Barrett's esophagus with varying degrees of dysplasia.

Authors
Garman, KS; Shaheen, NJ
MLA Citation
Garman, KS, and Shaheen, NJ. "Ablative therapies for Barrett's esophagus." Curr Gastroenterol Rep 13.3 (June 2011): 226-239. (Review)
PMID
21373836
Source
pubmed
Published In
Current Gastroenterology Reports
Volume
13
Issue
3
Publish Date
2011
Start Page
226
End Page
239
DOI
10.1007/s11894-011-0182-z

Colorectal Cancer Screening

Colorectal cancer screening is an important mission for a practicing gastroenterologist. Several different screening modalities are available: fecal occult blood test, flexible sigmoidoscopy, colonoscopy, barium enema, and more recently, CT-colonography and stool DNA tests. The physician is charged with weighing the pros and cons of the different screening methods and selecting the most appropriate method for each patient. © 2010 Blackwell Publishing Ltd.

Authors
Garman, KS; Provenzale, D
MLA Citation
Garman, KS, and Provenzale, D. "Colorectal Cancer Screening." (August 31, 2010): 212-218. (Chapter)
Source
scopus
Publish Date
2010
Start Page
212
End Page
218
DOI
10.1002/9781444328417.ch31

UK: price-based promotions target poor.

Authors
Garman, K; Tavakoly, B; Gilmore, A
MLA Citation
Garman, K, Tavakoly, B, and Gilmore, A. "UK: price-based promotions target poor." Tobacco control 19.4 (2010): 264-265.
PMID
20698056
Source
scival
Published In
Tobacco control
Volume
19
Issue
4
Publish Date
2010
Start Page
264
End Page
265

Leveraging time and learning style, iPod vs. realtime attendance at a series of medicine residents conferences: a randomised controlled trial.

OBJECTIVE: To determine whether participation in educational conferences utilising iPod technology enhances both medical knowledge and accessibility to educational content among medical residents in training. DESIGN/MEASUREMENTS: In May 2007, the authors led a randomised controlled study involving 30 internal medicine residents who volunteered either to attend five midday educational conferences or to use an iPod audio/video recording of the same conferences, each followed by a five-question competency quiz. Primary outcomes included quantitative assessment of knowledge acquisition and qualitative assessment of resident perception of ease of use. Secondary outcomes included resident perception of self-directed learning. RESULTS: At baseline, residents reported attendance at 50% of educational conferences. Of iPod participants, 46.7% previously used an iPod. During the study, 46-60% of conference attendees were paged out of each conference, of whom between 6 and 33% missed more than half of the conference. The quiz completion rate was 93%. Key findings were: 1) similar quiz scores were achieved by conference attendees, mean 60.7% (95% CI; 53.0-68.3%), compared to the iPod user group, mean 67.6% (95% CI; 61%-74.1%), and 2) the majority (10/15, 66.6%) of conference attendees stated they would probably benefit from the option to refer back to conferences for content review and educational purposes. CONCLUSIONS: Residency training programmes can optimise time management strategies with the integration of innovative learning resources into educational curricula. This study suggests that iPod capture of conferences is a reasonable resource to help meet the educational goals of residents and residency programs.

Authors
Tempelhof, MW; Garman, KS; Langman, MK; Adams, MB
MLA Citation
Tempelhof, MW, Garman, KS, Langman, MK, and Adams, MB. "Leveraging time and learning style, iPod vs. realtime attendance at a series of medicine residents conferences: a randomised controlled trial." Inform Prim Care 17.2 (2009): 87-94.
PMID
19807950
Source
pubmed
Published In
Informatics in primary care
Volume
17
Issue
2
Publish Date
2009
Start Page
87
End Page
94

Extraocular muscle dystonia due to acquired (non-Wilsonian) hepatocerebral degeneration

We present a video report of a patient with advanced non-Wilsonian cirrhotic liver disease who developed extraocular muscle dystonia (oculogyric crisis) and severe orofaciolingual dyskinesias. Acquired hepatocerebral degeneration causes choreic movements, especially of cranial muscles, but dystonic ocular spasm is an infrequent manifestation of this disorder. This case illustrates that AHD should be considered in the differential diagnosis of extraocular muscle dystonia. © 2008 Movement Disorder Society.

Authors
Ferrara, J; Gupta, D; Foster, E; Garman, K; Stacy, M
MLA Citation
Ferrara, J, Gupta, D, Foster, E, Garman, K, and Stacy, M. "Extraocular muscle dystonia due to acquired (non-Wilsonian) hepatocerebral degeneration." Movement Disorders 23.6 (2008): 875-878.
PMID
18361477
Source
scival
Published In
Movement Disorders
Volume
23
Issue
6
Publish Date
2008
Start Page
875
End Page
878
DOI
10.1002/mds.21841

Clinical diagnostic reasoning [14]

Authors
Echols, MR; Garman, KS; Lyles, KW
MLA Citation
Echols, MR, Garman, KS, and Lyles, KW. "Clinical diagnostic reasoning [14]." New England Journal of Medicine 356.12 (2007): 1272--.
PMID
17380583
Source
scival
Published In
The New England journal of medicine
Volume
356
Issue
12
Publish Date
2007
Start Page
1272-
DOI
10.1056/NEJMc063606

Colorectal cancer screening, comorbidity, and follow-up in elderly patients.

OBJECTIVE: We examined the relationship between comorbid disease and performance of complete colon examination by colonoscopy or double contrast barium enema (DCBE) after positive screening fecal occult blood test (FOBT) in patients 70 years of age or older. BACKGROUND: FOBT is an accepted form of colorectal cancer (CRC) screening. Factors that influence follow-up of positive FOBT have been largely unknown. METHODS: Patients aged 70 years and older with positive FOBT between March 1, 2000 and Feb 28, 2001 were included in this retrospective medical record review performed at a single center. Comorbidity was measured by the Charlson Comorbidity Scale. RESULTS: : In our sample of 266 subjects, 193 (73%) were referred for evaluation of positive FOBT and 109 (41%) underwent a colonoscopy or DCBE within 12 months. Using the Charlson score for comorbidity, 27% of our sample scored 0, 24% scored 1, and 23% scored 2 while 26% had a Charlson score of 3 or higher. There was no association between Charlson score (0, 1, 2, and > or =3) and referral for evaluation (chi test, P = 0.28) or performance of a complete colon examination (chi test, P = 0.38). CONCLUSIONS: In this sample, only 41% of patients with positive FOBT underwent a full colon examination within 12 months of a positive FOBT. Although comorbidity burden was considerable, there was no association between comorbidity score and referral for or performance of a full colon examination. These results suggest that inappropriate patients receive CRC screening, which may contribute to delays for screening appropriate patients and diagnostic delays for others with positive screening test findings.

Authors
Garman, KS; Jeffreys, A; Coffman, C; Fisher, DA
MLA Citation
Garman, KS, Jeffreys, A, Coffman, C, and Fisher, DA. "Colorectal cancer screening, comorbidity, and follow-up in elderly patients." Am J Med Sci 332.4 (October 2006): 159-163.
PMID
17031239
Source
pubmed
Published In
American Journal of the Medical Sciences
Volume
332
Issue
4
Publish Date
2006
Start Page
159
End Page
163

Colorectal cancer screening and follow-up in the elderly

Authors
Garman, KS; Jeffreys, A; Fisher, D
MLA Citation
Garman, KS, Jeffreys, A, and Fisher, D. "Colorectal cancer screening and follow-up in the elderly." October 2004.
Source
wos-lite
Published In
The American Journal of Gastroenterology (Elsevier)
Volume
99
Issue
10
Publish Date
2004
Start Page
S325
End Page
S325

Inpatient care for elderly cancer patients: the role for Geriatric Evaluation and Management Units in fulfilling goals for care.

PURPOSE: To describe patterns of functional status, symptoms, therapeutic goals and outcomes among older adults with cancer diagnoses hospitalized on a Geriatric Evaluation and Management Unit (GEMU). DESIGN AND METHODS: Retrospective chart review of veterans with a cancer diagnosis consecutively admitted to a Department of Veterans Affairs GEMU between 1996 and 1999. RESULTS: Thirty-six veterans with cancer diagnoses, average age of 80+/-5.0 years, 100% men, 50% white, 39% married were admitted during the target period. Comorbid illness was common (mean +/- S.D. = 4.6+/-2.0) as were associated symptoms (mean = 2.5+/-1.9). Average Karnofsky performance status was 55+/-7. Goals were accomplished 78% of the time for diagnosis, 73% for symptom management, 79% for functional improvement, and 100% for disposition/caregiver support. IMPLICATIONS: Elderly oncology patients admitted to a GEMU display diverse needs and goals that are realistic and attainable in this context. In-patient GEMU services represent a promising approach to care for older cancer patients, and deserve further evaluation of benefits and risks.

Authors
Garman, KS; McConnell, ES; Cohen, HJ
MLA Citation
Garman, KS, McConnell, ES, and Cohen, HJ. "Inpatient care for elderly cancer patients: the role for Geriatric Evaluation and Management Units in fulfilling goals for care." Crit Rev Oncol Hematol 51.3 (September 2004): 241-247.
PMID
15331081
Source
pubmed
Published In
Critical Reviews in Oncology/Hematology
Volume
51
Issue
3
Publish Date
2004
Start Page
241
End Page
247
DOI
10.1016/j.critrevonc.2004.03.002

Function in elderly cancer survivors depends on comorbidities.

BACKGROUND: Factors associated with functional status in elderly cancer survivors, in particular, comorbidity, have been inadequately studied. METHODS: Of 4162 participants aged 65 and older enrolled in the Duke Established Populations for Epidemiologic Studies of the Elderly study in 1986, 376 of the participants self-reported a diagnosis of cancer. Participants were divided into 2 comorbidity groups and 4 cancer groups. Cancer groups included 132 participants diagnosed 0-4 years ago, 117 diagnosed 5-15 years ago, 127 diagnosed >15 years ago, and 3784 participants who had never been diagnosed with cancer. Comorbidity (self-reported stroke, diabetes, hypertension, and myocardial infarction) was classified as presence of 1 or no comorbidities (n = 3089) or 2 or more comorbidities (n = 1073). Function was assessed by Katz Activities of Daily Living, Rosow-Breslau, Nagi, and Instrumental Activities of Daily Living scales at the time of interview. RESULTS: In a two-way analysis of covariance model of comorbidity and cancer group controlling for age, race, sex, education, marital status, depression, and cognitive status, duration of cancer survivorship does not influence most measures of function. In the subset of 376 cancer survivors, comorbidity significantly correlates with the functional status of these older cancer survivors (<0.02, for all 4 measures of function). CONCLUSIONS: In the older cancer survivor, regardless of duration following diagnosis, the presence of comorbidity rather than the history of cancer per se correlates with impaired functional status.

Authors
Garman, KS; Pieper, CF; Seo, P; Cohen, HJ
MLA Citation
Garman, KS, Pieper, CF, Seo, P, and Cohen, HJ. "Function in elderly cancer survivors depends on comorbidities." J Gerontol A Biol Sci Med Sci 58.12 (December 2003): M1119-M1124.
PMID
14684709
Source
pubmed
Published In
Journals of Gerontology: Series A
Volume
58
Issue
12
Publish Date
2003
Start Page
M1119
End Page
M1124

Functional status and the elderly cancer patient.

Evaluation of functional status plays a unique role in the assessment of older cancer patients. While performance status has been the traditional method for oncologists to assess the impact of a cancer patient's disease, older cancer patients may require a more thorough evaluation of their functional status. Evaluation of functional status provides information that can predict outcomes and may provide information that can be utilized to improve function. Functional status evaluation can be useful throughout the patient's illness, at the initial diagnostic evaluation, for determining appropriate therapies, for the monitoring of therapeutic effect and finally in the palliative phase. There are many different methods available to assess functional status. Individual assessment of functional status in the context of a geriatric assessment may be an important component of the care older cancer patients receive.

Authors
Garman, KS; Cohen, HJ
MLA Citation
Garman, KS, and Cohen, HJ. "Functional status and the elderly cancer patient." Crit Rev Oncol Hematol 43.3 (September 2002): 191-208. (Review)
PMID
12270776
Source
pubmed
Published In
Critical Reviews in Oncology/Hematology
Volume
43
Issue
3
Publish Date
2002
Start Page
191
End Page
208
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Research Areas:

  • Adenocarcinoma
  • Barrett Esophagus
  • Barrett's esophagus
  • Consumer behavior
  • Epithelial Cells
  • Esophageal Neoplasms
  • Mutation
  • Proteome