Faculty Bibliography

BACKGROUND: MLH1 is one of six known genes responsible for DNA mismatch repair (MMR), whose inactivation leads to HNPCC. It is important to develop genotype-phenotype correlations for HNPCC, as is being done for other hereditary cancer syndromes, in order to guide surveillance and treatment strategies in the future. CASE PRESENTATION: We report a 47 year-old male with hereditary nonpolyposis colorectal cancer (HNPCC) associated with a novel germline mutation in MLH1. This patient expressed a rare and severe phenotype characterized by three synchronous primary carcinomas: ascending and splenic flexure colon adenocarcinomas, and ureteral carcinoma. Ureteral neoplasms in HNPCC are most often associated with mutations in MSH2 and rarely with mutations in MLH1. The reported mutation is a two base pair insertion into exon 10 (c.866_867insCA), which results in a premature stop codon. CONCLUSION: Our case demonstrates that HNPCC patients with MLH1 mutations are also at risk for ureteral neoplasms, and therefore urological surveillance is essential. This case adds to the growing list of disease-causing MMR mutations, and contributes to the development of genotype-phenotype correlations essential for assessing individual cancer risk and tailoring of optimal surveillance strategies. Additionally, our case draws attention to limitations of the Amsterdam Criteria and the need to maintain a high index of suspicion when newly diagnosed colorectal cancer meets the Bethesda Criteria. Establishment of the diagnosis is the crucial first step in initiating appropriate surveillance for colorectal cancer and other HNPCC-associated tumors in at-risk individuals

Hepatic fibrosis occurs during most chronic liver diseases and is driven by inflammatory responses to injured tissue. Because DCs are central to modulating liver immunity, we postulated that altered DC function contributes to immunologic changes in hepatic fibrosis and affects the pathologic inflammatory milieu within the fibrotic liver. Using mouse models, we determined the contribution of DCs to altered hepatic immunity in fibrosis and investigated the role of DCs in modulating the inflammatory environment within the fibrotic liver. We found that DC depletion completely abrogated the elevated levels of many inflammatory mediators that are produced in the fibrotic liver. DCs represented approximately 25% of the fibrotic hepatic leukocytes and showed an elevated CD11b+CD8- fraction, a lower B220+ plasmacytoid fraction, and increased expression of MHC II and CD40. Moreover, after liver injury, DCs gained a marked capacity to induce hepatic stellate cells, NK cells, and T cells to mediate inflammation, proliferation, and production of potent immune responses. The proinflammatory and immunogenic effects of fibrotic DCs were contingent on their production of TNF-alpha. Therefore, modulating DC function may be an attractive approach to experimental therapeutics in fibro-inflammatory liver disease

BACKGROUND: Nearly 100,000 people await an organ transplant in the U.S. Improved utilization of potential organ donors may reduce the organ shortage. Physician attitudes toward organ donation may influence donation rates; however, the attitudes of U.S. physicians have not been formally evaluated. METHODS: Anonymous questionnaires were distributed to surgical attendings, surgical residents, and medical students at two academic medical centers. Willingness to donate one's own organs and family member's organs was examined, as well as experience with transplant procedures and religious views regarding organ donation. RESULTS: A total of 106 surveys were returned. Sixty-four percent of responders were willing to donate their own organs, and 49% had signed an organ donor card. Willingness to donate inversely correlated with professional experience. Eighty-four percent of those surveyed would agree to donate the organs of a family member, including 55% of those who refused to donate their own organs. Experience on the transplant service influenced 16% of those refusing donation, with the procurement procedure cited by 83% of this group. Sixteen percent refused organ donation on the basis of religious beliefs. CONCLUSIONS: The surveyed U.S. physicians are less willing to donate their organs compared with the general public. Despite understanding the critical need for organs, less than half of physicians surveyed had signed organ donor cards. Previous experiences with the procurement procedure influenced several responders to refuse organ donation. As the lay public traditionally looks to physicians for guidance, efforts must be made to improve physician attitudes toward organ donation with the hope of increasing donation rates

INTRODUCTION: This study was designed to compare symptomatic outcomes following cholecystectomy in patients with biliary dyskinesia. MATERIALS AND METHODS: From 1999 to 2006 at New York University Medical Center, 197 adults underwent hepatobiliary scintigraphy with cholecystokinin administration to evaluate gallbladder ejection fraction (GBEF). Biliary dyskinesia was demonstrated in 120 patients based on decreased GBEF of </=35%. Forty-four patients underwent cholecystectomy, and data from chart review and telephone questionnaires were available for 42 patients. Patients reported symptomatic improvement whether gallstones were present (25/27, 92.6%) or absent (13/15, 86.7%) prior to cholecystectomy (p = 0.90). The most common pathologic findings were chronic cholecystitis and cholesterolosis, regardless of the presence of gallstones. Additional data from 101 of the 120 patients with decreased GBEF demonstrated 74/101 (73.2%) patients were diagnosed with gastroesophageal reflux disease (GERD), and 59/101 (58.4%) patients were diagnosed with gastritis. RESULTS: The results of this study suggest that biliary dyskinesia should be considered as part of the spectrum of symptomatic gallbladder disease that can be successfully treated with cholecystectomy and that biliary dyskinesia is associated with GERD and gastritis

BACKGROUND: Traditionally, cholecystectomy for cholecystitis is performed within 3 days of the onset of symptoms or after 5 weeks, allowing for resolution of the inflammatory response. This study reviewed the outcomes of cholecystectomy performed for patients with gallstone disease in the acute (n = 45), intermediate (n = 55), and delayed (n = 102) periods after the onset of symptoms. METHODS: The medical records of 202 patients who underwent laparoscopic cholecystectomy at a large municipal hospital were reviewed retrospectively. The primary outcomes studied were length of hospital stay, conversion to open cholecystectomy, and complications. RESULTS: There was no significant difference in the conversion rate (acute [18%] vs intermediate [20%] vs delayed [11%]) or complication rate (acute [16%] vs intermediate [9%] vs delayed [7%]) among the 3 groups. The delayed group had a significantly shorter length of hospital stay than the intermediate or acute group (3.1 +/- 3.8 vs 4.3 +/- 3.8 vs 1.7 +/- 2.1, respectively, P < .001). CONCLUSIONS: Patients who present with acute symptoms of cholecystitis should undergo surgery during the same admission, regardless of the duration of symptoms