Toru Aoyama

Signatures of tumour immunity distinguish Asian and non-Asian gastric adenocarcinomas

Objective Differences in gastric cancer (GC) clinical outcomes between patients in Asian and non-Asian countries has been historically attributed to variability in clinical management. However, recent international Phase III trials suggest that even with standardised treatments, GC outcomes differ by geography. Here, we investigated gene expression differences between Asian and non-Asian GCs, and if these molecular differences might influence clinical outcome. Design We compared gene expression profiles of 1016 GCs from six Asian and three non-Asian GC cohorts, using a two-stage meta-analysis design and a novel biostatistical method (RUV-4) to adjust for technical variation between cohorts. We further validated our findings by computerised immunohistochemical analysis on two independent tissue microarray (TMA) cohorts from Asian and non-Asian localities (n=665). Results Gene signatures differentially expressed between Asians and non-Asian GCs were related to immune function and inflammation. Non-Asian GCs were significantly enriched in signatures related to T-cell biology, including CTLA-4 signalling. Similarly, in the TMA cohorts, non-Asian GCs showed significantly higher expression of T-cell markers (CD3, CD45R0, CD8) and lower expression of the immunosuppressive T-regulatory cell marker FOXP3 compared to Asian GCs (p<0.05). Inflammatory cell markers CD66b and CD68 also exhibited significant cohort differences (p<0.05). Exploratory analyses revealed a significant relationship between tumour immunity factors, geographic locality-specific prognosis, and postchemotherapy outcomes. Conclusions Analyses of >1600 GCs suggest that Asian and non-Asian GCs exhibit distinct tumour immunity signatures related to T-cell function. These differences may influence geographical differences in clinical outcome, and the design of future trials particularly in immuno-oncology.

Laparoscopic esophagojejunostomy using the EndoStitch and a circular stapler under a direct view created by the ENDOCAMELEON

Laparoscopic esophagojejunostomy using a circular stapler is associated with technical difficulties in the purse-string sutures used to insert the anvil head and in obtaining an adequate visual field to prevent rolling the mesentery and the wall of the jejunum on the mesenteric side into the anastomosis. To overcome these difficulties, we used the EndoStitch to create the purse-string suture and the ENDOCAMELEON to create the visual field to stretch the jejunum. After resecting the esophagus, purse-string sutures were placed using the EndoStitch. A total of five to six needle deliveries were performed. Next, the anvil head was inserted into the esophagus. The main unit of the EEA was inserted from the end of the resected jejunum. Then, the scope was changed to the ENDOCAMELEON. The main unit was slowly moved toward the anvil head. After making sure that the mesentery and the wall of the jejunum on the mesenteric side were not rolled into the anastomosis under the visual field created by the ENDOCAMELEON, the main unit was then fired. Thereafter, esophagojejunostomy was successfully completed. This technique was applied in 20 patients between April 2010 and May 2012. Laparoscopic esophagojejunostomy after total gastrectomy for gastric cancer was completed in all 20 patients. No case required conversion to open surgery. Neither anastomotic leakage nor stenosis was observed. This method is simple and useful for laparoscopic esophagojejunostomy after total gastrectomy for gastric cancer.

The survival difference between gastric cancer patients from the UK and Japan remains after weighted propensity score analysis considering all background factors

BackgroundPrevious studies comparing survival between gastric cancer (GC) patients from the West and the East were based on the assumption that background factors and prognostic factors were identical. The aim of the current study was to compare the survival of GC patients from the UK and Japan using weighted propensity score analysis after identifying all different background factors.MethodsData from 464 patients from the Leeds Teaching Hospital NHS Trust, Leeds, UK (LTHT), and 465 patients from the Kanagawa Cancer Center Hospital, Yokohama, Japan (KCCH), who had surgery for GC were analyzed. Prognostic factors for overall survival (OS) and cancer-specific survival (CSS) were identified by univariate and multivariate analyses. Survival was compared by propensity score weighting after adjusting for all significantly different background factors.ResultsMost background factors were different between LTHT and KCCH patients. Unadjusted stage-specific OS and CSS were significantly better in KCCH. Independent prognostic factors for unadjusted OS and CSS were pT and pN in KCCH and in addition tumor location, pancreatectomy, resection margin status and number of examined lymph nodes in LTHT. Even after adjusting for all background characteristics, survival remained better in KCCH.ConclusionsThese results suggest that differences in background factors are unable to fully explain the survival difference of GC patients between UK and Japan. Comprehensive studies into the biology of GC and/or host factors are needed to fully understand the survival difference.

Laparoscopy-Assisted Distal Gastrectomy for an Early Gastric Cancer Patient With Situs Inversus Totalis

Situs inversus totalis (SIT) is a congenital condition in which there is complete right to left reversal of the thoracic and abdominal organs. This report describes laparoscopy-assisted distal gastrectomy (LADG) for an early gastric cancer patient with SIT. The preoperative diagnosis was c-stage IA (cT1a cN0 cH0 cP0 cM0). LADG with D1+ dissection and Billroth-I reconstruction was successfully performed by standing at the opposite position. The operating time was 234 minutes and blood loss was 5 mL. Although a mechanical obstruction occurred after surgery, the patient recovered after re-operation with Roux-en-Y bypass.

Targeted therapy: Apatinib [mdash] new third-line option for refractory gastric or GEJ cancer

Apatinib significantly improves both the progression-free survival (PFS) and overall survival in patients with advanced-stage gastric cancer who are refractory to two or more lines of chemotherapy. In the context of previous phase III trials of angiogenesis inhibitors for this disease, we discuss the role of apatinib, and the advantages and limitations of VEGFR-2 blockade in the advanced disease setting.

Adjuvant therapy for locally advanced gastric cancer

D2 gastrectomy is now the globally accepted surgical standard for locally advanced gastric cancer. However, since 2000, different evidence has emerged regarding the efficacy of adjuvant chemoradiation, perioperative adjuvant chemotherapy, and postoperative chemotherapy for locally advanced gastric cancer. This review summarizes the background, current status, and future perspectives of adjuvant therapy for locally advanced gastric cancer. The Intergroup 0116 study was the first to show the significant overall survival benefits of adjuvant (chemoradiation) therapy for gastric cancer. The second study was the MAGIC trial, which showed the efficacy of perioperative adjuvant chemotherapy. Although the findings from the Intergroup 0116 study and the MAGIC trial were positive, recent studies, such as the ARTIST and EORTC 40954 studies, found no survival benefit for patients who had undergone D2 gastrectomy for gastric cancer. Regarding the adjuvant chemotherapy strategy, two pivotal phase III trials: the ACTS-GC and the CLASSIC, demonstrated the efficacy of postoperative adjuvant chemotherapy following D2 gastrectomy. However, more intensive chemotherapy is necessary to improve the survival rate. Several studies have analyzed the effectiveness of molecular-targeted therapy against metastatic gastric or gastroesophageal junction carcinoma. Further studies should focus on the survival benefit of more-intensive adjuvant therapy with D2 resection, or with concurrent molecular-targeted therapy.

Impact of postoperative complications on the colorectal cancer survival and recurrence: analyses of pooled individual patients’ data from three large phase III randomized trials

This study assessed the impact of postoperative complications on the colorectal cancer survival and recurrence after curative surgery using pooled individual patients’ data from three large phase III randomized trials. In total, 5530 patients were included in this study. The patients were classified as those with postoperative complications (C group) and those without postoperative complications (NC group). The risk factors for the overall survival (OS) and the disease‐free survival (DFS) were analyzed. Postoperative complications were found in 861 (15.6%) of the 5530 patients. The OS and DFS rates at 5 years after surgery were 68.9% and 74.8%, respectively, in the C group and 75.8% and 82.2%, respectively, in the NC group, values that were significantly different between the two groups (P < 0.001). The multivariate analysis demonstrated that postoperative complications were a significant independent risk factor for the OS and DFS. Postoperative complications can worsen the colorectal cancer survival and risk of recurrence. Surgical morbidity must be considered as a stratification factor in future phase III trials evaluating the effects of adjuvant chemotherapy on colorectal cancer.

Randomized clinical trial comparing standard diet with perioperative oral immunonutrition in total gastrectomy for gastric cancer

Total gastrectomy for gastric cancer is associated with excessive weight loss and decreased calorie intake. Nutritional support using eicosapentaenoic acid modulates immune function and limits catabolism in patients with advanced cancer, but its impact in the perioperative period is unclear.

Phase II study on hepatic arterial infusion chemotherapy using percutaneous catheter placement techniques for liver metastases from colorectal cancer (JFMC28 study)

This prospective multicenter study aimed to evaluate the efficacy and adverse events of hepatic arterial infusion chemotherapy (HAIC) using percutaneous catheter placement techniques for liver metastases from colorectal cancer (CRC).

Prognostic factors in stage IB gastric cancer.

AIM To identify the subset of patients with stage IB gastric cancer with an unfavorable prognosis. METHODS Overall survival (OS) rates were examined in 103 patients with stage IB (T1N1M0 and T2N0M0) gastric cancer between January 2000 and December 2011. Univariate and multivariate analyses were performed to identify risk factors using a Cox proportional hazards model. RESULTS The OS rates of patients with T1N1 and T2N0 cancer were 89.2% and 94.1% at 5-years, respectively. Both univariate and multivariate analyses demonstrated that tumor location was the only significant prognostic factor. The OS rate was 81.8% at 5-years when the tumor was located in the upper third of the stomach and was 95.5% at 5-years when the tumor was located in the middle or lower third of the stomach (P = 0.0093). CONCLUSION These data may suggest that tumor location is associated with survival in patients with stage IB gastric cancer.