Trinitia Cannon

The Department of Veterans Affairs Laryngeal Cancer Study propelled the combination of chemotherapy and radiation therapy to the forefront of strategies used for the management of locally advanced laryngeal cancer. The organ preservation rate was 84%. However, over the past 30 years that these approaches have been in place, there have been concerns regarding long-term survival and high failure rates requiring salvage. Furthermore, salvage laryngectomy, if feasible when considering increased morbidity after CRT, is fraught with a higher risk of wound complications including fistula, longer hospitalization, and reduced quality of life.

BACKGROUND: Pharyngocutaneous fistula (PCF) and salivary leaks are well known complications of head and neck surgery. The medical management of PCF has included the use of octreotide without a well-defined understanding of its therapeutic mechanism. We hypothesized that octreotide induces alterations in the saliva proteome and that these alterations may provide insight into the mechanism of action underlying improved PCF healing. We undertook an exploratory pilot study in healthy controls that involved collecting saliva before and after a subcutaneous injection of octreotide and performing proteomic analysis to determine the effects of octreotide. METHODS: Four healthy adult participants provided saliva samples before and after subcutaneous injection of octreotide. A mass-spectrometry based workflow optimized for the quantitative proteomic analysis of biofluids was then employed to analyze changes in salivary protein abundance after octreotide administration. RESULTS: There were 3076 human, 332 Streptococcus mitis, 102 G. haemolyans, and 42 Granulicatella adiacens protein groups quantified in saliva samples. A paired statistical analysis was performed using the generalized linear model (glm) function in edgeR. There were and ~300 proteins that had a p < .05 between the pre- and post-octreotide groups ~50 proteins with an FDR-corrected p < .05 between pre- and post-groups. These results were visualized using a volcano plot after filtering on proteins quantified by 2 more or unique precursors. Both human and bacterial proteins were among the proteins altered by octreotide treatment. Notably, four isoforms of the human cystatins, belonging to a family of cysteine proteases, that had significantly lower abundance after treatment. CONCLUSION: This pilot study demonstrated octreotide-induced downregulation of cystatins. By downregulation of cystatins in the saliva, there is decreased inhibition of cysteine proteases such as Cathepsin S. This results in increased cysteine protease activity that has been linked to enhanced angiogenic response, cell proliferation and migration that have resulted in improved wound healing. These insights provide first steps at furthering our understanding of octreotide's effects on saliva and reports of improved PCF healing.

OBJECTIVES: To evaluate patients 25 years of age or younger who were treated for nasopharyngeal carcinoma. STUDY DESIGN: Retrospective review, systematic literature review. METHODS: Nasopharyngeal carcinoma (NPC) is rare in the Western world. In people younger than 30 years, it is even less common, with an incidence of 1 to 2 per million. This retrospective study was designed to analyze the outcomes of patients 25 years of age or younger who were treated for NPC at a tertiary care academic medical center. Between November 1982 and December 2004, 15 patients meeting the above criteria were treated. These patients form the basis for this report. A systematic review of all NPC trials published in the United States since 1990 was done and the results compared with those of our cohort. RESULTS: Young African Americans represented 67% of the 15 cases seen at our institution and between 55% and 67% of the patients in the United States. With a mean follow-up of 5.36 years, disease-free survival and overall survival rates were 67% and 87%, respectively. Locoregional control was excellent after treatment with cisplatin-based combination chemoradiotherapy; however, four patients (27%) developed distant metastasis. Despite this, no patients died of disease. Toxicity was significant but manageable, and retreatment met with good success. CONCLUSIONS: In patients 25 years of age or younger, NPC is more common in African Americans. This may represent a genetic and racial predisposition of this unusual disease in the United States. Late-stage presentations and distant recurrences are common. Platinum-based combination chemoradiotherapy and aggressive management of metastatic disease, however, is associated with good long-term survival. Further study of the possibly changing epidemiology and racial genetics of this unusual tumor is warranted.

Background: Larynx cancer is a common site for tumors of the upper aerodigestive tract. In cases with a clinically negative neck, the indications for an elective neck treatment are still debated. The objective is to define the prevalence of occult metastasis based on the subsite of the primary tumor, T classification and neck node levels involved. Methods: All studies included provided the rate of occult metastases in cN0 larynx squamous cell carcinoma patients. The main outcome was the incidence of occult metastasis. The pooled incidence was calculated with random effects analysis. Results: 36 studies with 3803 patients fulfilled the criteria. The incidence of lymph node metastases for supraglottic and glottic tumors was 19.9% (95% CI 16.4–23.4) and 8.0% (95% CI 2.7–13.3), respectively. The incidence of occult metastasis for level I, level IV and level V was 2.4% (95% CI 0–6.1%), 2.0% (95% CI 0.9–3.1) and 0.4% (95% CI 0–1.0%), respectively. For all tumors, the incidence for sublevel IIB was 0.5% (95% CI 0–1.3). Conclusions: The incidence of occult lymph node metastasis is higher in supraglottic and T3–4 tumors. Level I and V and sublevel IIB should not be routinely included in the elective neck treatment of cN0 laryngeal cancer and, in addition, level IV should not be routinely included in cases of supraglottic tumors.