Survival after inflammatory bowel disease-associated colorectal cancer in the Colon Cancer Family Registry

AIM: To investigate the survival of individuals with colorectal cancer (CRC) with inflammatory bowel disease (IBD-associated CRC) compared to that of individuals without IBD diagnosed with CRC. METHODS: Epidemiologic, clinical, and follow-up data were obtained from the Colon Cancer Family Registry (Colon CFR). IBD-associated cases were identified from self-report of physician diagnosis. For a subset of participants, medical records were examined to confirm self-report of IBD. Cox proportional hazards regression was applied to estimate adjusted hazard ratios (aHR) and 95%CI of mortality, comparing IBD-associated to non-IBD-associated CRC, adjusted for age at CRC diagnosis, sex, Colon CFR phase, and number of prior endoscopies. Following imputation to complete CRC stage information, adjustment for CRC stage was examined. RESULTS: A total of 7202 CRC cases, including 250 cases of IBD-associated CRC, were analyzed. Over a twelve year follow-up period following CRC diagnosis, 2013 and 74 deaths occurred among non-IBD associated CRC and IBD-associated CRC patients, respectively. The difference in survival between IBD-associated and non-IBD CRC cases was not statistically significant (aHR = 1.08; 95%CI: 0.85-1.36). However, the assumption of proportional hazards necessary for valid inference from Cox regression was not met over the entire follow-up period, and we therefore limited analyses to within five years after CRC diagnosis when the assumption of proportional hazards was met. Over this period, there was evidence of worse prognosis for IBD-associated CRC (aHR = 1.36; 95%CI: 1.05-1.76). Results were similar when adjusted for CRC stage, or restricted to IBD confirmed in medical records. CONCLUSION: These results support the hypothesis that IBD-associated CRC has a worse prognosis than non-IBD-associated CRC.

Germline BRCA2 variants in advanced pancreatic acinar cell carcinoma:A case report and review of literature

BACKGROUND Pancreatic acinar cell carcinoma(PACC)is a rare tumor.Up to 45%of PACCs have alterations in the DNA damage repair pathway and 23%harbor rearrangements in the BRAF or RAF1 genes.We present a PACC case with a germline BRCA2 likely pathogenic variant(LPV)to highlight the impact of genomic testing on treatment decisions and patient outcomes.In our larger case series,we provide clinic-based information on additional 10 PACC patients treated in our center.CASE SUMMARY A 70-year-old male was diagnosed with advanced PACC.At presentation,he was cachectic with severe arthralgia despite prednisolone and a skin rash that was later confirmed to be panniculitis.He was treated with modified FOLFIRINOX(mFFX)with the knowledge of the germline BRCA2 LPV.Following 11 cycles of mFFX,a computed tomography(CT)scan demonstrated significant tumor response in the pancreatic primary and hepatic metastases,totaling 70%from baseline as per Response Evaluation Criteria in Solid Tumors.Resolution of the skin panniculitis was also noted.We identified two additional PACCs with druggable targets in our case series.Our data contribute to practical evidence for the value of germline and somatic profiling in the management of rare diseases like PACC.CONCLUSION This patient and others in our larger case series highlight the importance of genomic testing in PACC with potential utility in personalized treatment.