Gastrointestinal cancer research : GCR最新文献

Background: The 5-year survival of pancreatic adenocarcinoma with surgery and adjuvant chemotherapy is below 25%. The original Gastrointestinal Tumor Study Group (GITSG) adjuvant study demonstrated a survival benefit attributed to weekly intravenous boluses of 5-fluorouracil (5-FU) for 2 years in addition to chemoradiation compared to surgery alone. In theory, the prolonged exposure to therapy could maintain pressure on dormant cancer cells that remain in G0 arrest and kill them as they infrequently enter the G1/S phase. We retrospectively evaluated outcomes in patients who were treated with adjuvant chemotherapy and maintenance capecitabine compared with those who received only adjuvant chemotherapy.

Methods: Patients who had undergone surgical resection with curative intent and received adjuvant chemotherapy were analyzed. Those who subsequently received maintenance capecitabine therapy were compared to those who received adjuvant chemotherapy only. The primary end points were disease recurrence and all-cause mortality.

Results: The median overall survival (OS) of patients receiving maintenance capecitabine was greater than 48.4 months (the exact estimate was not available, since the survival probability curve does not cross 0.5). It was 22.0 months (95% confidence interval [CI], 16.6-29.2) in patients who received adjuvant chemotherapy only (P < .001 by log-rank test). The median recurrence-free survival (RFS) was also longer in the maintenance capecitabine group: 54.3 (95% CI, 22.2-Inf) compared to 14.1 (95% CI, 11.6-16.7) months (P < .001, by log-rank test).

Conclusions: In this retrospective study, patients with resected pancreatic adenocarcinoma who received adjuvant chemotherapy had improved OS and RFS with additional maintenance therapy with capecitabine. These findings should be confirmed with a randomized, controlled trial.

Background: Anaplastic lymphoma kinase (ALK) fusion oncogenes are present in multiple cancer types. The inversion of echinoderm microtubule-associated protein-like 4 (EML4) and anaplastic lymphoma kinase (ALK) genes on chromosome 2 is present in a subset of patients with non-small-cell lung cancer (NSCLC). ALK-rearranged lung cancers demonstrate a significantly higher incidence of signet ring cell histology than do ALK-negative tumors. Based on the histologic similarities of ALK-rearranged NSCLC and signet ring cell carcinomas (SRCCs) of the gastrointestinal tract, we hypothesized that SRCC of the upper gastrointestinal (GI) tract may also harbor ALK translocations.

Methods: Thirty-five formalin-fixed, paraffin-embedded (FFPE) diagnostic tissue specimens of SRCC or poorly differentiated adenocarcinoma with greater than 10% signet ring cell features originating from the upper GI tract were obtained and confirmed by a board-certified, GI pathologist. SRCC specimens were analyzed by fluorescence in situ hybridization (FISH) analysis, with an ALK (2p23) break-apart probe.

Results: The FISH analysis revealed no evidence of ALK translocation. All 35 (100%) SRCC specimens showed intact ALK FISH signals.

Conclusions: These data indicate that, despite histologic similarities between SRCC of the upper GI tract and ALK-positive NSCLC, ALK translocations are unlikely to be a significant contributor to the molecular etiology of SRCC. Further genomic investigations are ongoing.

Background: The HER2/neu gene is a proto-oncogene that can predict the response to treatment with trastuzumab, pertuzumab, and lapatinib. This study was conducted to determine the frequency of HER2/neu overexpression and to identify a subgroup of patients with gallbladder cancer who would benefit from targeted therapy.

Methods: Patients with gallbladder cancer (n = 187; 165 women and 22 men) with a recorded follow-up of at least 5 years were included, along with control subjects (n = 75). An automated immunohistochemical technique was used with an anti-ErbB2 antibody. Scoring was conducted according to the CAP/ASCO (College of American Pathologists/American Society of Clinical Oncology) criteria for breast cancer.

Results: Overexpression of HER2/neu was observed in 12.8% of the cases. Of those, 0% were mucosal, 14.3% muscular, 12.8% subserosal, and 10.6% serosal. In 20% of the cases, equivocal staining was observed. Overexpression was more frequent in the advanced cancers and in the better differentiated tumors (13.8% and 17.4%, respectively), but the difference was nonsignificant. The patients with overexpression of HER2/neu had a worse overall survival, when compared with those who had no expression at 5 years (34% vs. 41%).

Conclusion: This is the single largest study of HER2/neu expression in gallbladder cancer to use commonly accepted scoring criteria. The results indicate that HER2/neu overexpression occurred in 14% of the advanced gallbladder cancer cases. This subgroup may benefit from inhibitors of the HER2/neu pathway.

Background: Emerging data suggest that the fibrolamellar variant of hepatocellular carcinoma (FL-HCC) differs in clinical course and prognosis from conventional (nonfibrolamellar) HCC (NFL-HCC). Although FL-HCC is believed to have a better prognosis than NFL-HCC, data comparing the prognoses of the two types of HCC remain lacking. The aim of this systematic review was to compare the prognosis of FL- vs. NFL-HCC.

Methods: Two of the authors independently conducted a comprehensive search of the Cochrane Library, PubMed, Scopus, and published proceedings from major hepatology and gastrointestinal meetings from January 1980 to October 2013. Outcomes of interest were mean overall survival (OS) and 5-year survival. The analyses were performed with a fixed- or random-effects model, as appropriate. The Begg's and Egger's tests with visual inspection of the funnel plot were used to assess for population bias. All analyses were performed with RevMan 5.1 (Cochrane IMS).

Results: Seventeen studies involving 368 patients with FL-HCC and 9877 patients with NFL-HCC were included in the analysis. There was an overall statistically significant increase in the 5-year survival for the FL-HCC vs. the NFL-HCC patients (RR, 2.09; 95% CI, 1.38-3.16). In a subgroup analysis limited to noncirrhotic patients, there was no significant difference in 5-year survival in the FL-HCC group compared to that in the NFL-HCC group (RR, 1.69; 95% CI, 0.69-4.17). A significant increase in mean OS was reported in patients with FL-HCC compared with the survival time of those with NFL-HCC (84.9 ± 15.8 vs. 42.9 ± 6.5 months) undergoing partial hepatectomy, but there was no difference in patients undergoing liver transplantation (51.4 ± 14.4 vs. 47.5 ± 5.5 months).

Conclusion: Patients with FL-HCC treated with hepatic resection had significantly higher 5-year survival rates than did those with NFL-HCC. However, survival was similar for both FL-HCC and conventional HCC in noncirrhotic patients. There seems to be no difference in survival outcomes for FL- and NFL-HCC when transplantation is used as the therapeutic option.