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Background: The AJCC staging for pancreatic cancer is relatively non-discriminatory for prediction of survival after resection. At the Moffitt Cancer Center a prognostic score for patients with localized pancreatic cancer (AJCC <= IIb) has been developed. In the Moffitt Prognostic Index (MPI) patients are grouped in 5 risk categories on the basis of extra-pancreatic tumor extension, degree of differentiation and lymphatic invasion. The aim of this study is to assess the MPI's predictive value in an independent cohort of patients who underwent pancreaticoduodenectomy (PD) at the New York University. Methods From our retrospective pancreatic adenocarcinoma database of 248 patients, we identified and grouped by MPI category patients with AJCC stage <= IIb who underwent PD (1990-2009). Differences between groups were evaluated using ANOVA and chi-squared test. Overall survival (OS) for each group was estimated using the Kaplan-Meier method and compared using the log-rank statistic. Results Among 131 patients with stage Ia-IIb cancer, MPI could be calculated for 126 (96%). Only few patients fell in MPI lower-risk groups 1- 4 (respectively 1, 4, 3, 22), while the majority (96, 76.1%) fell in MPI group 5 (poor prognosis). The 5 groups were similar in demographics, underlying comorbidities, laboratory data, ASA score and ECOG performance status. There were no differences in operative time, blood loss, intra- and post-operative complications, length of stay, 30-day mortality. Pathology revealed more advanced stage in groups 3 to 5 (p=0.001). At mean follow-up of 18 months, there was no difference in median OS across MPI groups (respectively 19, 6, 16, 17, 12 months, p=0.91). Of note, AJCC staging did correlate with median OS (respectively 43, 12, 16, 11 months in stages Ia to IIb, p = 0.004). Conclusions In our experience the MPI performed worse than AJCC staging as a prognostic tool. The clustering of patients in the worst-prognosis group defied the very purpose of prognosis discrimination. Furthermore, in our experience MPI did not correlate with overall survival in patients undergoing DP for earlystage (<= IIb) pancreatic cancer

Colorectal cancer (CRC) is the second most common cause of cancer-related death in the United States. CRC, however, is potentially preventable, and several strategies may be employed to decrease the incidence of and mortality from CRC. Understanding of individual risk and adherence to screening and surveillance recommendations undoubtedly will reduce CRC-associated deaths. Several natural and synthetic chemopreventive agents may prove effective for both primary and secondary CRC chemoprevention. Finally, dietary modifications (ie, increased dietary fiber, fruits and vegetables, and decreased red meat) and other lifestyle changes (i.e., increased physical activity, weight maintenance, avoidance of smoking, and moderation of alcohol intake) also may lower the risk of developing CRC

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

OBJECTIVE: This study summarizes our initial experience with prospective, single-amplicon (mutation-specific) A636P testing in Ashkenazi Jewish patients at risk for Hereditary Nonpolyposis Colorectal Cancer (HNPCC). SUMMARY BACKGROUND DATA: We previously described a founder mutation, MSH2*1906G >C (A636P) that causes HNPCC in 8/1345 (0.59%) of Ashkenazim with colorectal cancer. The mutation was more common in Ashkenazim diagnosed at <or=40 years (7%). METHODS: Twenty-seven Ashkenazi probands at risk for HNPCC were ascertained. Single-amplicon A636P testing was performed on 21 by polymerase chain reaction of exon 12 of MSH2, followed by direct DNA sequencing. Mutational analysis of the entire open reading frame of MLH1 and MSH2 was performed on 7 by PCR of each exon, followed by heteroduplex analysis using denaturing high-performance liquid chromatography and direct sequencing of exons with variant chromatographs. One patient received both studies, RESULTS: The A636P mutation was detected in 3/21 (14%) prospectively evaluated patients using single amplicon testing. In 6 patients, the entire open reading frame of MLH1 and MSH2 was analyzed, and 1 additional A636P carrier and 2 carriers of previously unrecognized mutations were identified. The A636P mutation was present in 2 patients who met Amsterdam criteria and in 2 patients who did not. CONCLUSIONS: Although rare in the general population, A636P mutations are found at increased frequency in Ashkenazim with a personal or family history of colorectal or other HNPCC-associated cancers. This inexpensive and rapid approach may be useful preoperatively in helping determine the extent of colon resection for a subset of patients