89 Background: There is a lack of predictive markers informing on the risk of colitis in patients... more 89 Background: There is a lack of predictive markers informing on the risk of colitis in patients treated with immune checkpoint inhibitors (ICIs). The aim of this study was to identify potential factors associated with development of ICI colitis. Methods: We performed a retrospective analysis of melanoma patients at Dana-Farber Cancer Institute who received PD-1, CTLA-4, or combination blockade between May 2011 to October 2017. Clinical and laboratory characteristics associated with pathologically confirmed ICI colitis were evaluated using multivariate logistic regression analyses. External validation was performed on an independent cohort from Massachusetts General Hospital. Results: The discovery cohort included 213 patients of whom 37 developed ICI colitis (17%). The odds of colitis were higher in patients treated with ipilimumab either as monotherapy or in combination with nivolumab compared to those treated with pembrolizumab. Vitamin D use was recorded in 66/213 patients (31%...
Serrated polyps compromise both typical hyperplastic polyps as well as sessile serrated adenomas ... more Serrated polyps compromise both typical hyperplastic polyps as well as sessile serrated adenomas and dysplastic serrated polyps. Hyperplastic polyps exhibit two histological patterns: microvesicular hyperplastic polyps (MVHPs) and goblet cell hyperplastic polyps (GCHPs). MVHPs and GCHPs differ in their molecular signature. MVHPs have been frequently found to have the BRAF(V600E) mutation as well as aberrant methylation. In contrast, GCHPs have been associated with the KRAS mutation (KRAS-mut), which are infrequently seen in dysplastic serrated sessile adenomas. The particular risk factors that are associated with development of the types of hyperplastic polyps have not been previously studied. The purpose of this study is to characterize the associations between particular risk factors and the development of goblet cell or microvesicular hyperplastic polyps. We conducted a cross-sectional analysis of 3,543 asymptomatic, mostly average risk patients 50 and 79 years of age undergoing open-access screening colonoscopy between March 2005 and January 2012. Each patient was given a survey regarding 25 reputed risk factors for colorectal neoplasia and the responses were correlated with findings at colonoscopy. Associations between putative risk factors for colorectal neoplasia and MVHPs and GSHPs were examined using multiple logistic regression. MVHPS and GCHPs were identified in 5.3% and 8.7% of patients, respectively. The results of the statistical analysis indicate that a history of smoking greater than 20 years is associated with an increased risk of MVHPs (P<0.005) and GCHPs (P<0.005). An elevated BMI >30 kg/m(2) was also associated with the presence of MVHP at colonoscopy (P<0.005). Blacks and Asians appear to be protected from the development of MVHPs. In contrast, there was a positive association with the presence of GCHP at colonoscopy in blacks. The study suggests that the development of the distinct histological types of hyperplastic polyps are associated with distinct modifiable and non-modifiable lifestyle factors.
89 Background: There is a lack of predictive markers informing on the risk of colitis in patients... more 89 Background: There is a lack of predictive markers informing on the risk of colitis in patients treated with immune checkpoint inhibitors (ICIs). The aim of this study was to identify potential factors associated with development of ICI colitis. Methods: We performed a retrospective analysis of melanoma patients at Dana-Farber Cancer Institute who received PD-1, CTLA-4, or combination blockade between May 2011 to October 2017. Clinical and laboratory characteristics associated with pathologically confirmed ICI colitis were evaluated using multivariate logistic regression analyses. External validation was performed on an independent cohort from Massachusetts General Hospital. Results: The discovery cohort included 213 patients of whom 37 developed ICI colitis (17%). The odds of colitis were higher in patients treated with ipilimumab either as monotherapy or in combination with nivolumab compared to those treated with pembrolizumab. Vitamin D use was recorded in 66/213 patients (31%...
Serrated polyps compromise both typical hyperplastic polyps as well as sessile serrated adenomas ... more Serrated polyps compromise both typical hyperplastic polyps as well as sessile serrated adenomas and dysplastic serrated polyps. Hyperplastic polyps exhibit two histological patterns: microvesicular hyperplastic polyps (MVHPs) and goblet cell hyperplastic polyps (GCHPs). MVHPs and GCHPs differ in their molecular signature. MVHPs have been frequently found to have the BRAF(V600E) mutation as well as aberrant methylation. In contrast, GCHPs have been associated with the KRAS mutation (KRAS-mut), which are infrequently seen in dysplastic serrated sessile adenomas. The particular risk factors that are associated with development of the types of hyperplastic polyps have not been previously studied. The purpose of this study is to characterize the associations between particular risk factors and the development of goblet cell or microvesicular hyperplastic polyps. We conducted a cross-sectional analysis of 3,543 asymptomatic, mostly average risk patients 50 and 79 years of age undergoing open-access screening colonoscopy between March 2005 and January 2012. Each patient was given a survey regarding 25 reputed risk factors for colorectal neoplasia and the responses were correlated with findings at colonoscopy. Associations between putative risk factors for colorectal neoplasia and MVHPs and GSHPs were examined using multiple logistic regression. MVHPS and GCHPs were identified in 5.3% and 8.7% of patients, respectively. The results of the statistical analysis indicate that a history of smoking greater than 20 years is associated with an increased risk of MVHPs (P<0.005) and GCHPs (P<0.005). An elevated BMI >30 kg/m(2) was also associated with the presence of MVHP at colonoscopy (P<0.005). Blacks and Asians appear to be protected from the development of MVHPs. In contrast, there was a positive association with the presence of GCHP at colonoscopy in blacks. The study suggests that the development of the distinct histological types of hyperplastic polyps are associated with distinct modifiable and non-modifiable lifestyle factors.
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