Background Quantitative computed tomography (CT) assessment of visceral adiposity may be superior to body mass index (BMI) as a predictor of surgical morbidity. We sought to examine the association of CT measures of obesity and BMI with short-term post-operative outcomes in colon cancer patients. Methods In this retrospective study, 110 patients treated with colectomy for Stage I–III colon cancer were classified as obese or non-obese by pre-operative CT-based measures of adiposity or BMI. [Obese: BMI≥30kg/m2, visceral fat area (VFA) to subcutaneous fat area ratio (V/S) ≥0.4 and VFA>100cm2)]. Post-operative morbidity and mortality rates were compared. Results Obese patients, by V/S and VFA but not BMI, were more likely to be male and have pre-existing hypertension and diabetes. The overall complication rate was 25.5% and there were no mortalities. Obese patients by VFA (with a trend for VS but not BMI) were more likely to develop postoperative complications as compared to patients classified as non-obese; VFA (30.5% vs.10.7%, p= 0.03), VS (29.2% vs. 9.5%, p=0.05) and BMI (32.4% vs. 21.9%, p=0.23). Conclusions Elevated visceral obesity quantified by CT is associated with the presence of key metabolic comorbidities and increased post-operative morbidity and may be superior to BMI for risk stratification.

Background The incidence and outcomes for patients with colorectal cancer (CRC) varies by age. Younger patients tend to have sporadic cancers not detected by screening and worse survival. To understand if genetic differences exist between age cohorts we sought to characterize unique genetic alterations in patients with CRC. Methods We identified 283 patients with sporadic CRC between 1998 and 2010 and divided them by age into two cohorts: ≤45 years old (younger) or ≥65 years old (older) and performed targeted exome sequencing. Fisher’s Exact test was used to detect differences in mutation frequencies between the two groups. Whole exome sequencing was performed on 21 additional younger patient samples for validation. Findings were confirmed in The Cancer Genome Atlas CRC dataset. Results 246 samples were included for final analysis (195 older, 51 younger). Mutations in FBXW7 were more common in the younger cohort (27.5% vs. 9.7%, p=0.0022) as were mutations in the proofreading domain of POLE (9.8% vs. 1.0%, p= 0.0048). There were similar mutation rates between cohorts with regards to TP53 (64.7% vs. 61.5%), KRAS (43.1% vs. 46.2%), and APC (60.8% vs 73.8%). BRAF mutations were numerically more common in the older cohort, though not statistically significant (2.0% vs 9.7%, p=0.082). Conclusions In this retrospective study, we identified a unique genetic profile for younger CRC patients as compared to patients diagnosed at an older age. These findings should be validated in a larger study and could have an impact on future screening and treatment modalities for younger CRC patients.

This chapter describes the potential use of flavopiridol, a CDK inhibitor with anti-inflammatory and anti-proliferative activities, in the treatment of various chronic diseases. Flavopiridol arrests cell cycle progression in the G1 or G2 phase by inhibiting the kinase activities of CDK1, CDK2, CDK4/6, and CDK7. Additionally, it binds tightly to CDK9, a component of the P-TEFb complex (CDK9/cyclin T), and interferes with RNA polymerase II activation and associated transcription. This in turn inhibits expression of several pro-survival and anti-apoptotic genes, and enhances cytotoxicity in transformed cells or differentiation in growth-arrested cells. Recent studies indicate that flavopiridol elicits anti-inflammatory activity via CDK9 and NFκB-dependent signaling. Overall, these effects of flavopiridol potentiate its ability to overcome aberrant cell cycle activation and/or inflammatory stimuli, which are mediators of various chronic diseases.

No abstract

Synchronous cancers of different primary origin are rare. Here, we describe the case of a patient with concomitant diagnoses of rectal adenocarcinoma and splenic marginal zone lymphoma (smzl).A 57-year-old woman initially presented with abdominal pain. Physical examination and computed tomography demonstrated massive splenomegaly, and a complete blood count revealed microcytic anemia and lymphopenia. During the subsequent evaluation, she presented with hematochezia, melena, and constipation, which prompted gastroenterology referral. Subsequent endoscopic rectal ultrasonography revealed a T3N1 moderately differentiated rectal adenocarcinoma, with computed tomography imaging of chest, abdomen, and pelvis confirming no metastasis. Thus, the cancer was classified as clinical stage T3N1M0, stage iii. Bone marrow biopsy confirmed co-existing marginal zone lymphoma, and with the clinical presentation of massive splenomegaly, a diagnosis of smzl was made.The patient's management was individually tailored for simultaneous optimal treatment of both conditions. Concurrent treatment with neoadjuvant rituximab and 5-fluorouracil chemotherapy, with external-beam radiation therapy to the pelvis, was administered, followed by surgery consisting of en bloc splenectomy and distal pancreatectomy, and low anterior resection. The patient completed a standard course of adjuvant folfox (fluorouracil-leucovorin-oxaliplatin) chemotherapy and has remained disease-free for 7 years.To our knowledge, this report is the first to specifically describe simultaneous diagnoses of locally advanced rectal cancer and smzl. We also describe the successful combined neoadjuvant treatment combination of 5-fluorouracil, rituximab, and pelvic radiation.