Taikan Yamamoto

Molecular differences between sporadic serrated and conventional colorectal adenomas.

Purpose: The purpose is to compare the molecular characteristics of serrated adenomas (SAs) with those of conventional adenomas (CADs) and hyperplastic polyps (HPs). Experimental Design: We evaluated the proliferative activity and molecular alterations in 47 SAs (25 pure-type and 22 mixed-type), 71 CADs, and 23 HPs. Results: The proliferative activity of SAs, as evaluated by Ki-67 expression, was intermediate between CADs and HPs. There was no significant difference in the incidence of KRAS or p53 mutations between the three histological groups. In the microsatellite instability (MSI) analysis, 21% of SAs (9 of 43) showed MSI at two or more loci (MSI-H); corresponding values were 5% of CADs (3 of 64) and 8% of HPs (1 of 13; SAs versus CADs, P = 0.0125). MSI-H was more likely to be found in pure-type SAs (36%; 8 of 22) than in mixed-type SAs (5%; 1 of 21; P = 0.0212). Loss of hMLH-1 expression was found in 8 of 9 SAs with MSI-H. The incidence of BRAF or KRAS mutations was 36 and 15% of SAs, respectively; the combined incidence of BRAF and KRAS mutations occurred in 49% of SAs. However, there was no significant difference in the incidence of BRAF or KRAS mutations between SAs with and without MSI-H. Conclusions: Genetic instability is more frequently implicated in the tumorigenesis of SAs, especially pure-type SAs, than in that of CADs. In contrast, activation of the Ras/Raf/MEK/MAP kinase cascade by BRAF or KRAS mutation, independently of the genetic instability, may be associated with the progression of about half of SAs.

Early tumor shrinkage as a predictor of favorable outcomes in patients (pts) with advanced pancreatic cancer treated with FOLFIRINOX.

237 Background: Results from the phase III PRODIGE 4/ACCORD 11 trial provided one of current standard regimens for advanced pancreatic cancer (PC), consisting of oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX), which has superior response rate (RR) and survival benefit even with severe toxicity (Thierry C, et al. N Engl J Med 2011;364:1817-1825). There are several reports on the correlation between early tumor shrinkage (ETS) or depth of response (DpR) and survival in chemotherapies for colorectal cancer; however, few studies have investigated it in PC. We therefore analyzed retrospectively whether the ETS will predict outcomes in pts with PC treated with FOLFIRINOX therapy. Methods: Advanced PC pts with ECOG PS of 0 or 1, who received FOLFIRINOX as 1st- or 2nd-line treatment between November 2012 and July 2015 in 3 institutes of Showa University were included in this analysis. ETS was defined as a reduction ≥ 20% of target lesions’ diameters measured at 8 weeks from treatment start. We...

Efficacy of chemotherapy after self-expanding metal stent placement for gastric outlet obstruction caused by an unresectable malignant tumor.

484 Background: Gastric outlet obstruction (GOO) is a late complication of advanced and metastatic malignant tumors. Self-expanding metal stent (SEMS) placement is a safe and effective palliative treatment for patients with GOO. In general, the median survival time after SEMS placement for GOO is approximately 90 days, and advanced chemotherapeutic treatment could further improve prognosis. Methods: This retrospective study aimed to analyze the efficacy of chemotherapy after SEMS placement on improvement of oral intake and survival time. Eight patients with symptomatic malignant GOO were treated by SEMS placement in our hospital. Surgical bypass could not be performed due to severe advanced malignant tumors. Patients were classified into two groups depending on whether they received chemotherapy after SEMS placement. Group A included five patients who were treated with palliative therapy alone (median age: 72 years; cases 1, 2, 3, and 4 with advanced gastric cancer, and case 5 with advanced pancreatic car...