Masakatsu Numata

The clinicopathological features of colorectal mucinous adenocarcinoma and a therapeutic strategy for the disease

BackgroundThe guidelines established by the National Comprehensive Cancer Network do not describe mucinous histology as a clinical factor that should influence the therapeutic algorithm. However, previous studies show conflicting results regarding the prognosis of colorectal mucinous adenocarcinoma. In this study, we described the clinicopathological features of mucinous adenocarcinoma in Japan, to identify optimal therapeutic strategies.Methods144 patients with mucinous and 2673 with non-mucinous adenocarcinomas who underwent primary resection in two major centers in Yokohama, Japan were retrospectively evaluated for clinicopathological features and treatment factors. A multivariate analysis for overall survival followed by the comparison of overall survival using Cox proportional hazard model were performed.ResultsPatients with mucinous adenocarcinoma had larger primary lesions, higher preoperative CEA levels, a deeper depth of invasion, higher rates of nodal and distant metastasis, and more metastatic sites. A multivariate analysis for overall survival revealed a mucinous histology to be an independent prognostic factor. In the subgroup analysis stratified by stage, Patients diagnosed as StageIII and IV disease had a worse survival in mucinous adenocarcinoma than non-mucinous, while survival did not differ significantly in patients diagnosed as Stage0-II disease. In StageIII, local recurrence in rectal cases and peritoneal dissemination were more frequently observed in patients with a mucinous histology.ConclusionsOur study indentified that mucinous adenocarcinoma was associated with a worse survival compared with non-mucinous in patients with StageIII and IV disease. In rectal StageIII disease with mucinous histology, additional therapy to control local recurrence followed by surgical resection may be a strategical alternative. Further molecular investigations considering genetic features of mucinous histology will lead to drug development and better management of peritoneal metastasis

The clinical significance of SWI/SNF complex in pancreatic cancer

Chromatin remodeling factors have been the subject of great interest in oncology. However, little is known about their role in pancreatic cancer. The objective of this study was to clarify the clinical significance of the SWItch/sucrose nonfermentable (SWI/SNF) complex in patients with pancreatic cancer. A total of 68 patients with pancreatic cancer who underwent R0, 1 resection were enrolled. Cancer tissues were processed to tissue microarray, then stained immunohistochemically by using antibody of SWI/SNF components; BRM, BRG1, BAF250a, BAF180 and BAF47. The correlation of expression levels and clinicopathological outcomes were analyzed, followed by the multivariate analysis of prognostic factors for overall survival. The expression levels of the SWI/SNF components were categorized as low or high according to the median value of Histoscore. Statistical analysis revealed that BRM expression was related to tumor size, T factor, M factor, lymphatic invasion and stage BRG1 expression to histology and stage BAF180 expression to tumor size and BAF47 expression to lymphatic invasion, respectively. Multivariate Cox proportional hazard analysis showed that high BRM and low BAF180 expression levels were independent predictors of worse survival in patients with pancreatic cancer. High BRM, and low BAF180 were also independent prognostic factors for poor survival in the subgroup with adjuvant gemcitabine. These results suggest that the specific cofactors of SWI/SNF chromatin remodeling complex certainly have roles in pancreatic cancer. High BRM, and low BAF180 are useful biomarkers for poor prognosis in pancreatic cancer.

The cellular level of histone H3 lysine 4 dimethylation correlates with response to adjuvant gemcitabine in Japanese pancreatic cancer patients treated with surgery

BACKGROUND To search for biomarkers identifying pancreatic cancer patients likely to benefit from adjuvant gemcitabine chemotherapy, we investigated the status of several histone modifications in pancreatic tumors and their relationship to clinicopathological features and outcomes. METHODS Sixty one pancreatic cancer patients, primarily treated by surgical removal of tumors, were involved in the study. Thirty patients completed postoperative adjuvant gemcitabine, and in 31 it was discontinued. Tumor specimens were examined using immunohistochemistry for di- and tri-methylation of histone H3 lysine 4 (H3K4me2 and H3K4me3), dimethylation and acetylation of histone H3 lysine 9 (H3K9me2 and H3K9ac), and acetylation of histone H3 lysine 18 (H3K18ac). Positive tumor staining for each histone modification was used to classify patients into low- and high-staining groups, which were examined for relationships to clinicopathological features and clinical outcomes. RESULTS High expression of H3K4me3 was related to the well and moderately differentiated tumor histological type (p = 0.012) and low expression of H3K4me2 was related to the presence of perineural invasion (p = 0.007). No cellular histone modifications were associated with overall or disease-free survival of patients as a whole. In the subgroup analyses, a low level of H3K4me2 was significantly associated with worse disease free survival in patients that completed adjuvant gemcitabine (p = 0.0239). Univariate and multivariate hazard models also indicated that a low level of H3K4me2 was a significant independent predictor of disease-free survival (p = 0.007). CONCLUSION H3K4me2 was found to be a predictor of response to adjuvant gemcitabine in Asian patients with pancreatic cancer.

A propensity score-matching analysis comparing the oncological outcomes of laparoscopic and open surgery in patients with Stage I/II colon and upper rectal cancers

PurposePrevious studies from Western countries have shown similar survival outcomes after both open and laparoscopic resections. In Japan, radical D3 dissections performed by open resection have been routinely performed for ≥T2- or ≥N1-stage cancers, and relatively favorable survival outcomes were obtained. This study compared the survival in patients with Stage I/II colon and upper rectal cancers undergoing laparoscopic and open resection.MethodsA total of 145 patients were initially enrolled. Propensity score matching was applied to assemble a study cohort. D2 lymph node dissection for T1 cancer and D3 for ≥T2- and ≥N1-stage cancers were applied. The primary outcome measure was the disease-free survival; the cancer-specific and overall survival rates were secondary outcomes.ResultsA total of 64 patients were matched for the analysis. The length of hospitalization, postoperative complication rates, number of lymph nodes removed and surgical margins were similar between the groups. The disease-free survival following laparoscopic surgery was better than that following open surgery, but the difference was not statistically significant. Neither the cancer-specific nor overall survival rates following laparoscopic surgery were inferior to those associated with open surgery.ConclusionsThe outcomes of the laparoscopic approach were comparable to those for open surgeries accompanied by radical lymph node dissection.

Evaluation of short-term outcomes of laparoscopic-assisted surgery for colorectal cancer in elderly patients aged over 75 years old: a multi-institutional study (YSURG1401)

BackgroundThe short-term outcomes of laparoscopic-assisted surgery for colorectal cancer (LAC) have not been fully evaluated in elderly patients. The aim of this study was to compare the short term surgical outcomes of LAC between the patients older than 75 years and those with non-elderly patients.MethodsThis retrospective multi-institutional study selected patients who underwent LAC between April 2013 and March 2014 at Yokohama City University Hospital and its related general hospitals. The patients were categorized into two groups: elderly patients (>75 years of age: group A) and non-elderly patients (<75 years of age: group B). Surgical outcomes and post operative complications were compared between the two groups.ResultsA total of 237 patients were evaluated in the present study. Eighty-four patients were classified into group A, and 153 into group B. Preoperative clinicopathological outcomes demonstrated no significant differences except for the ASA score. When comparing the surgical outcomes between group A and group B, the rate of conversion to open procedure (3.6% vs 5.2%, P = 0.750), median operation time (232 min vs 232 min, P = 0.320), median blood loss (20 ml vs 12 ml, P = 0.350). The differences were not significantly different in the surgical outcomes. The incidences of > grade 2 post operative surgical complications were similar between two groups ((19.0% vs 15.7%, p = 0.587). No mortality was observed in this study. The length of postoperative hospital stay was also similar (10 days vs 10 days, p = 0.350).ConclusionsThe present study suggested that LAC is safe and feasible, regardless of the age of the patient, especially for elderly patients who may be candidates for colon cancer surgery.

Significance of regenerating islet-derived type IV gene expression in gastroenterological cancers

The regenerating islet-derived members (Reg), a group of small secretory proteins, which are involved in cell proliferation or differentiation in digestive organs, are upregulated in several gastrointestinal cancers, functioning as trophic or antiapoptotic factors. Regenerating islet-derived type IV (RegIV), a member of the Reg gene family, has been reported to be overexpressed in gastroenterological cancers. RegIV overexpression in tumor cells has been associated with carcinogenesis, cell growth, survival and resistance to apoptosis. Cancer tissue expressing RegIV is generally associated with more malignant characteristics than that without such expression, and RegIV is considered a novel prognostic factor as well as diagnostic marker in some gastroenterological cancers. We previously investigated the expression levels of RegIV mRNA of 202 surgical colorectal cancer specimens with quantitative real-time reverse-transcriptase polymerase chain reaction and reported that a higher level of RegIV gene expression was a significant independent predictor of colorectal cancer. The biologic functions of RegIV protein in cancer tissue, associated with carcinogenesis, anti-apoptosis and invasiveness, are being elucidated by molecular investigations using transfection techniques or neutralizing antibodies of RegIV, and the feasibility of antibody therapy targeting RegIV is being assessed. These studies may lead to novel therapeutic strategies for gastroenterological cancers expressing RegIV. This review article summarizes the current information related to biological functions as well as clinical importance of RegIV gene to clarify the significance of RegIV expression in gastroenterological cancers.

A Case of Adenomyomatous Hyperplasia of the Extrahepatic Bile Duct

Adenomyomatous hyperplasia is rarely found in the extrahepatic bile duct. A 54-year-old man was referred to our center with a diagnosis of extrahepatic bile duct stenosis which had been detected by endoscopic retrograde choloangiopancreatography. Abdominal computed tomography revealed thickening of the wall of the middle extrahepatic bile duct, however no malignant cells were detected by cytology. Since bile duct carcinoma could not be ruled out, we performed resection of the extrahepatic duct accompanied by lymph node dissection. Histopathologically, the lesion was diagnosed as adenomyomatous hyperplasia of the extrahepatic bile duct. Present and previously reported cases showed the difficulty of making a diagnosis of adenomyomatous hyperplasia of the extrahepatic bile duct preoperatively or intraoperatively. Therefore, when adenomyomatous hyperplasia is suspected, a radical surgical procedure according to malignant disease may be necessary for definitive diagnosis.

Safety and feasibility of laparoscopic reoperation for treatment of anastomotic leakage after laparoscopic colorectal cancer surgery: Laparoscopic reoperation for leakage

The safety and feasibility of laparoscopic reoperation for anastomotic leakage remain unclear.

The Lymph Node Ratio Is an Independent Prognostic Factor in Pancreatic Cancer Patients Who Receive Curative Resection Followed by Adjuvant Chemotherapy

Background/Aim: The present study investigated the impact of the lymph node ratio (LNR) on survival and recurrence in patients with pancreatic cancer after curative surgery followed by adjuvant chemotherapy. Patients and Methods: This study included 189 patients who underwent curative surgery followed by adjuvant chemotherapy for pancreatic cancer between 2005 and 2014. The risk factors for overall survival (OS) and recurrence-free survival (RFS) were identified. Results: A lymph node ratio of 0.1 was considered to be the optimal cut-off point for classification based on the 3-year and 5-year survival rates. The OS rates at three and five years after surgery were 34.4% and 28.2% in the LNR <0.1 group, respectively, and 23.1% and 5.8% in the LNR ≥0.1 group, which amounted to a statistically significant difference (p=0.003). The RFS rates at one and three years after surgery were 26.6% and 20.5% in the LNR <0.1 group, respectively, and 8.0% and 0% in the LNR ≥0.1 group, which was a significant difference (p=0.001). A multivariate analysis demonstrated that the LNR was a significant independent risk factor for both the OS and RFS. Conclusion: The LNR was a risk factor for overall survival in patients who underwent curative surgery followed by adjuvant chemotherapy for pancreatic cancer. It is necessary to develop strategies to effectively utilize the lymph node metastasis status.

Safety of Laparoscopic Surgery for Colorectal Cancer in Patients with Severe Comorbidities

Background/Aim: Previous studies have shown that laparoscopic colorectal cancer surgery is highly safe and effective compared to laparotomy. However, whether laparoscopic colorectal cancer surgery can be safely performed in patients with severe comorbidities remains unclear. The aim of this study was to evaluate the safety of laparoscopic colorectal cancer surgery in patients with severe comorbidities. Patients and Methods: A total of 82 consecutive patients with colorectal cancer who underwent laparoscopic surgery were retrospectively divided into two groups according to whether they had severe comorbidity (50 patients) or non-severe comorbidity (32 patients). An age-adjusted Charlson comorbidity index of ≥6 was defined as severe comorbidity. Results: Operative time, blood loss, and rate of conversion to laparotomy did not differ between the groups. Postoperative complications and the length of the postoperative hospital stay also did not differ significantly between the groups. Conclusion: Laparoscopic colorectal cancer surgery is feasible and safe, even in patients with severe comorbidities.