Faculty Bibliography

Over half of patients with human immunodeficiency virus (HIV) experience diarrhea that contributes negatively to quality of life and adherence to antiretroviral therapy (ART). Opportunistic infectious agents that cause diarrhea in patients with HIV span the array of protozoa, fungi, viruses, and bacteria. With global use of ART, the incidence of diarrhea because of opportunistic infections has decreased; however, the incidence of noninfectious diarrhea has increased. The etiology of noninfectious diarrhea in patients with HIV is multifactorial and includes ART-associated diarrhea and gastrointestinal damage related to HIV infection (i.e., HIV enteropathy). A basic algorithm for the diagnosis of diarrhea in patients with HIV includes physical examination, a review of medical history, assessment of HIV viral load and CD4+ T cell count, stool microbiologic assessment, and endoscopic evaluation, if needed. For patients with negative diagnostic results, the diagnosis of noninfectious diarrhea may be considered. Pharmacologic options for the treatment of noninfectious diarrhea are primarily supportive; however, the use of many unapproved agents is based on unstudied and anecdotal information. In addition, these agents can be associated with treatment-limiting adverse events (AEs), such as drug-drug interactions with ART regimens, abuse liability, and additional gastrointestinal AEs. Currently, crofelemer, an antisecretory agent, is the only therapy approved in the USA for the symptomatic relief of noninfectious diarrhea in patients with HIV on ART.

BACKGROUND: The aim of this study was to examine the role of Ki-67, a cellular proliferation marker, in the prognosis of goblet cell appendiceal carcinoid tumor. METHODS: Twelve goblet cell appendiceal carcinoid tumors were stained with MIB-1, a monoclonal antibody of Ki-67, to assess their cell proliferation and correlations with clinical and histologic parameters. RESULTS: Among 12 patients studied, the mean MIB-1 index was 24%, with tumors ranging from .5 to 5.0 cm in size. No correlation was observed between tumor size and MIB-1 index. Two patients had metastatic disease on presentation (MIB-1 index 10% and 60%). All patients received surgical intervention according to extent of tumor invasion regardless of their MIB-1 index values. Median follow-up was 54 months, with a 75% follow-up rate and 1 death from metastasis. The overall survival rate was 76%, with a disease-specific survival rate of 87%. CONCLUSIONS: Ki-67 had no prognostic significance for goblet cell carcinoid tumors and should not be used solely to determine treatment and surgical approach.

GOALS: To assess prospectively the bleeding risk attributable to gastroduodenal biopsy in subjects taking antiplatelet medications. BACKGROUND: No prospective data exist regarding the bleeding risk attributable to endoscopic biopsy in patients taking antiplatelet agents. A majority of Western endoscopists withdraw antiplatelet agents before upper endoscopy, despite expert guidelines to the contrary. STUDY: We performed a prospective, single-blind, randomized study in healthy volunteers participating in a larger study regarding the effect of antiplatelet agents on gastroduodenal mucosal healing. Multiple gastroduodenal biopsies were performed during 2 esophagogastroduodenoscopy in subjects dosed with aspirin enteric-coated 81 mg once daily or clopidogrel 75 mg once daily. Data for endoscopic bleeding, clinical bleeding, blood vessel size, and depth of biopsy in histology specimens were collected. RESULTS: Four hundred and five antral biopsies and 225 duodenal biopsies were performed during 90 esophagogastroduodenoscopy in 45 subjects receiving aspirin or clopidogrel. Median maximum blood vessel diameter per biopsy was 31.9 mu (range: 9.2 to 133.8). About 50.8% of biopsy specimens breached the muscularis mucosa. In the clopidogrel group, no bleeding events were noted after 350 biopsies [upper confidence limit (UCL) for probability of bleeding=0.0085]. In the aspirin group, there were no clinical events (UCL=0.0106) and one minor endoscopic bleeding event (UCL=0.0169). CONCLUSIONS: Consistent with expert guidelines, the absolute risk attributable to gastroduodenal biopsy in adults taking antiplatelet agents seems to be low. Half of routine biopsies enter submucosa. The largest blood vessels avulsed during biopsy correspond to midsized and large arterioles and venules.

BACKGROUND/OBJECTIVE: To elucidate the correlation of Ki-67 with tumor biology and survival in appendiceal carcinoid tumors. METHOD: A retrospective chart review conducted on 51 patients with appendiceal carcinoid tumors who underwent surgical intervention from 1991 to 2008. MIB-1, an antibody of Ki-67, was used to determine cell proliferation and correlated with clinical and histological parameters. MIB-1 index was categorized according to the World Health Organization (WHO) classification. RESULT: Of the 51 patients, 32 had tumors <2 cm; 3 >2 cm; and 16 with unspecified tumor size. Increased MIB proliferative index did not significantly correlate with increasing tumor size (P = 0.426). Twelve patients had metastatic disease on presentation: 9 had MIB-1 index <2%, 1 had index 2-15% and 2 with index >15%. No significant correlation between MIB index and metastasis was demonstrated (P = 0.68). Median follow-up was 40 months (range 10-183 months) with a 51% follow-up rate. Seven mortalities and three recurrences presented in 26 patients. Assessment of survival demonstrated significantly decreased survival by increasing MIB index. Survival rate by MIB index was as follows: <2% was 97%, 2-15% was 85% and >15% was 67% (P = 0.02). CONCLUSION: Increased MIB index significantly correlated with decreased survival. No correlation was demonstrated by MIB index and tumor size or presentation with metastatic disease.

PURPOSE: The purpose of this study was to determine the long-term survival rate, rate of gastrointestinal continuity restoration, and rate of recurrence following an attack of fulminant Clostridium difficile colitis. MATERIAL AND METHODS: Fulminant C. difficile colitis was defined as any patient who had a bout of C. difficile colitis and required surgical intervention after failing medical therapy. These patients were found through a pathological database search. Follow-up phone calls were made to any patient who survived at least 30 days after being discharged from the hospital following surgical intervention (long-term survivor group). RESULTS: A total of 49 patients were involved in the study. The 30-day mortality rate was 57% (28/49), with an in-hospital mortality rate of 49%. The 5-year survival rate for the long-term survival group was 38% (8/21) and 16.3% for all patients. Gastrointestinal continuity was restored in 20% of the patients. There was one documented recurrence of C. difficile colitis CONCLUSION: Patients who have a bout of fulminant C. difficile colitis have a poor prognosis of surviving longer than 5 years. Restoring gastrointestinal continuity is uncommon and usually reserved for patients with few co-morbidities. Recurrent C. difficile colitis after surgical resection is a rare occurrence.