Totally Laparoscopic Gastrectomy for Gastric Cancer Associated with Recklinghausen's Disease

This paper documents the first case of gastric cancer associated with Recklinghausen's disease, which was successfully treated by a totally laparoscopic operation. A 67-year-old woman with Recklinghausen's disease was referred to this department to undergo surgical treatment for early gastric cancer. The physical examination showed multiple cutaneous neurofibromas throughout the body surface, which made an upper abdominal incision impossible. Laparoscopic surgery requiring only small incisions was well indicated, and a totally laparoscopic distal gastrectomy with lymph node dissection was performed. Billroth I reconstruction was done intra-abdominally using a delta-shaped anastomosis. The patient followed a satisfactory postoperative course with no complications. Since the totally laparoscopic gastrectomy has many advantages over open surgery, it should therefore be preferentially used as a less invasive treatment in the field of gastric cancer

Treatment results of two-stage operation for the patients with esophageal cancer concomitant with liver dysfunction

Purpose : The aim of this study was to clarify the usefulness of two-stage operation for the patients with esophageal cancer who have liver dysfunction. Methods : Eight patients with esophageal cancer concomitant with liver dysfunction who underwent two-stage operation were analyzed. The patients initially underwent an esophagectomy, a cervical esophagostomy and a tube jejunostomy, and reconstruction with gastric tube was performed after the recovery of patients’ condition. Results : The average time of the 1st and 2nd stage operation was 410.0 min and 438.9 min, respectively. The average amount of blood loss in the 1st and 2nd stage operation was 433.5 ml and 1556.8 ml, respectively. The average duration between the operations was 29.8 days. The antesternal route was selected for 5 patients (62.5%) and the retrosternal route was for 3 patients (37.5%). In the 1st stage operation, no postoperative complications were observed, while, complications developed in 5 (62.5%) patients, including 4 anastomotic leakages, after the 2nd stage operation. Pneumonia was not observed through two-stage operation. No in-hospital death was experienced. Conclusion : A two-stage operation might prevent the occurrence of critical postoperative complications for the patients with esophageal cancer concomitant with liver dysfunction

Fibroblast growth factor receptor 2 expression, but not its genetic amplification, is associated with tumor growth and worse survival in esophagogastric junction adenocarcinoma

Background: Fibroblast growth factor receptor 2 (FGFR2) genetic alterations lead to tumor cell proliferation in various types of cancer. We hypothesized that FGFR2 amplification is associated with FGFR2 expression, resulting in tumor growth and poorer outcome in esophagogastric junction (EGJ) adenocarcinoma. Patients and Methods A total of 176 consecutive chemo-naive patients with EGJ adenocarcinoma were enrolled from two academic institutions. FGFR2 amplification was examined by real-time PCR (N = 140) and FGFR2 expression with immunohistochemical staining (N = 176), and compared against clinicopathological factors and patient outcomes. The effects of FGFR2 inhibition or overexpression on cell proliferation, cell cycle, and apoptosis assays were investigated in EGJ adenocarcinoma cell lines. Downstream FGFR2, AKT and ERK were also examined. Results: Based on the correlation between FGFR2 levels and FGFR2 overexpression in vitro, FGFR2 amplification was defined as copy number > 3.0. In clinical samples, FGFR2 amplification and FGFR2 IHC expression were 15% and 61%, respectively. Although these two statuses were significantly correlated (P < 0.05), only FGFR2 IHC expression was significantly associated with tumor depth (multivariate P < 0.001) and overall survival of patients (univariate P = 0.007). Supporting these findings, FGFR2 overexpression was associated with tumor cell proliferation, cell cycle progression, and anti-apoptosis. Selective inhibition of FGFR2 sufficiently suppressed tumor cell proliferation through de-phosphorylation of AKT and ERK. Conclusions: FGFR2 amplification was significantly associated with FGFR2 expression. FGFR2 expression (but not FGFR2 amplification) was associated with tumor growth and patient outcomes. Our findings support FGFR2 as a novel therapeutic target for EGJ adenocarcinoma

CTDSP1 inhibitor rabeprazole regulates DNA-PKcs dependent topoisomerase I degradation and irinotecan drug resistance in colorectal cancer.

Irinotecan specifically targets topoisomerase I (topoI), and is used to treat various solid tumors, but only 13-32% of patients respond to the therapy. Now, it is understood that the rapid rate of topoI degradation in response to irinotecan causes irinotecan resistance. We have published that the deregulated DNA-PKcs kinase cascade ensures rapid degradation of topoI and is at the core of the drug resistance mechanism of topoI inhibitors, including irinotecan. We also identified CTD small phosphatase 1 (CTDSP1) (a nuclear phosphatase) as a primary upstream regulator of DNA-PKcs in response to topoI inhibitors. Previous reports showed that rabeprazole, a proton pump inhibitor (PPI) inhibits CTDSP1 activity. The purpose of this study was to confirm the effects of rabeprazole on CTDSP1 activity and its impact on irinotecan-based therapy in colon cancer. Using differentially expressing CTDSP1 cells, we demonstrated that CTDSP1 contributes to the irinotecan sensitivity by preventing topoI degradation. Retrospective analysis of patients receiving irinotecan with or without rabeprazole has shown the effects of CTDSP1 on irinotecan response. These results indicate that CTDSP1 promotes sensitivity to irinotecan and rabeprazole prevents this effect, resulting in drug resistance. To ensure the best chance at effective treatment, rabeprazole may not be a suitable PPI for cancer patients treated with irinotecan