野田 弘志

BACKGROUND: Surgical site infection is one of the most common postoperative complications after gastroenterologic surgery. This study investigated the effect of triclosan-coated sutures in decreasing the incidence of surgical site infections after abdominal wall closure in gastroenterologic surgery. METHODS: A prospective, double-blind, randomized, controlled parallel adaptive group-sequential superiority trial was conducted from March 2014 to March 2017 in a single center. Eligible patients were those who underwent gastroenterologic surgery. Patients were allocated randomly to receive either abdominal wall closure with triclosan-coated sutures (the study group) or sutures without triclosan (the control group). The primary end point was the incidence of superficial or deep surgical site infections within 30 days after operation. This study was registered with the University Hospital Medical Information Network-Clinical Trials Registry (http://www.umin.ac.jp/ctr/), identification number UMIN000013054. RESULTS: A total of 1,013 patients (study group, 508 patients; control group, 505 patients) were analyzed by a modified intention-to-treat approach. The wounds in 990 (97.7%) of the 1,013 patients were classified as clean-contaminated. The primary end point (incidence of superficial or deep surgical site infections) was 35 (6.9%) of 508 patients in the study group and 30 (5.9%) of 505 in the control group. The incidence of surgical site infections did not differ markedly between the 2 groups (95% confidence interval: 0.686-2.010, P = .609). Of the 65 infections, 42 (64.6%) were superficial surgical site infections, with similar frequencies in the 2 groups, and 23 (35.4%) were deep surgical site infections, again with similar frequencies in the 2 groups. CONCLUSION: Triclosan-coated sutures did not decrease the incidence of surgical site infections after abdominal wall closure in gastroenterologic surgery.

症例は60代女性。1991年他院で後腹膜脂肪肉腫に対して腫瘍摘出術および補助化学療法を施行された。1999年3月右腎臓下極近傍の再発に対して右腎摘出術を伴う再発腫瘍摘出術を当院で施行。その後、2006年1月肝臓尾側の再発、2008年6月腹部大動脈腹側の再発、2015年10月右側腹部の再発に対して各々、再発腫瘍摘出術を施行し、初回手術から25年の現在無再発生存中である。脂肪肉腫の予後は組織型に依存し、高分化型脂肪肉腫は予後良好である。高分化型脂肪肉腫においては外科的切除の可否が予後に反映し、再発を来しても、完全切除することで予後改善が期待できるため、術後の綿密な経過観察による早期再発診断、再発腫瘍摘出術の施行が重要である。(著者抄録)

症例は70代女性。上腹部痛と嘔吐を契機に胆嚢腫瘍を指摘された。膵胆管合流異常に合併した胆嚢癌の診断で胆嚢床切除術を施行。術後病理組織学的検査で胆嚢癌肉腫の診断となった。術後6ヵ月で肝転移再発を認めS-1療法、gemcitabine療法を施行。progressive diseaseであったが、他に新出病変を認めなかったため、肝切除を行った。術後gemcitabine療法施行し、初回手術後32ヵ月無再発生存中である。癌肉腫は上皮性悪性腫瘍の癌と非上皮性悪性腫瘍の肉腫が混在する腫瘍で、胆嚢原発の癌肉腫はまれな腫瘍である。本疾患は再発が多く予後不良であるが再発に対する有効な治療法は未だ確立されていない。今回、胆嚢癌肉腫の術後肝転移再発に対して、化学療法と肝切除を行い、病勢をコントロールしている1例を経験した。本症例は治癒切除が可能な胆嚢癌肉腫転移再発例に対する治療としての切除の有効性を示唆すると考えられた。(著者抄録)

AIM To assess the usefulness of en bloc right hemicolectomy with pancreaticoduodenectomy (RHCPD) for locally advanced right-sided colon cancer (LARCC). METHODS We retrospectively reviewed the database of Saitama Medical Center, Jichi Medical University, between January 2009 and December 2016. During this time, 299 patients underwent radical right hemicolectomy for right-sided colon cancer. Among them, 5 underwent RHCPD for LARCC with tumor infiltration to adjacent organs. Preoperative computed tomography (CT) was routinely performed to evaluate local tumor infiltration into adjacent organs. During the operation, we evaluated the resectability and the amount of infiltration into the adjacent organs without dissecting the adherent organs from the cancer. When we confirmed that radical resection was feasible and could lead to R0 resection, we performed RHCPD. The clinical data were carefully reviewed, and the demographic variables, intraoperative data, and postoperative parameters were recorded. RESULTS The median age of the 5 patients who underwent RHCPD for LARCC was 70 years. The tumors were located in the ascending colon (three patients) and transverse colon (two patients). Preoperative CT revealed infiltration of the tumor into the duodenum in all patients, the pancreas in four patients, the superior mesenteric vein (SMV) in two patients, and tumor thrombosis in the SMV in one patient. We performed RHCPD plus SMV resection in three patients. Major postoperative complications occurred in 3 patients (60%) as pancreatic fistula (grade B and grade C, according to International Study Group on Pancreatic Fistula Definition) and delayed gastric empty. None of the patients died during their hospital stay. A histological examination confirmed malignant infiltration into the duodenum and/ or pancreas in 4 patients (80%), and no patients showed any malignant infiltration into the SMV. Two patients were histologically confirmed to have tumor thrombosis in the SMV. All of the tumors had clear resection margins (R0). The median follow-up time was 77 mo. During this period, two patients with tumor thrombosis died from liver metastasis. The overall survival rates were 80% at 1 year and 60% at 5 years. All patients with node-negative status (n = 2) survived for more than seven years. CONCLUSION This study showed that the long-term survival is possible for patients with LARCC if RHCPD is performed successfully, particularly in those with node-negative status.

Morphological response is considered an improved surrogate to the Response Evaluation Criteria in Solid Tumors (RECIST) model with regard to predicting the prognosis for patients with colorectal liver metastases. However, its use as a decision-making tool for surgical intervention has not been examined. The present study assessed the morphological response in 50 patients who underwent chemotherapy with or without bevacizumab for initially un-resectable colorectal liver metastases. Changes in tumor morphology between heterogeneous with uncertain borders and homogeneous with clear borders were defined as an optimal response (OR). Patients were also assessed as having an incomplete response (IR), and an absence of marked changes was assessed as no response (NR). No significant difference was observed in progression-free survival (PFS) between complete response/partial response (CR/PR) and stable disease/progressive disease (SD/PD), according to RECIST. By contrast, PFS for OR/IR patients was significantly improved compared with that for NR patients (13.2 vs. 8.7 months; P=0.0426). Exclusion of PD enhanced the difference in PFS between OR/IR and NR patients (15.1 vs. 9.3 months; P<0.0001), whereas no difference was observed between CR/PR and SD. The rate of OR and IR in patients treated with bevacizumab was 47.4% (9/19), but only 19.4% (6/31) for patients that were not administered bevacizumab. Comparison of the survival curves between OR/IR and NR patients revealed similar survival rates at 6 months after chemotherapy, but the groups exhibited different survival rates subsequent to this period of time. Patients showing OR/IR within 6 months appeared to be oncologically stable and could be considered as candidates for surgical intervention, including rescue liver resection. Comparing the pathological and morphological features of the tumor with representative optimal response, living tumor cells were revealed to be distributed within the area of vascular reconstruction induced by bevacizumab, resulting in a predictive value for prognosis in the patients treated with bevacizumab. The present findings provided the evidence for physicians to consider patients with previously un-resectable metastatic colorectal cancer as candidates for surgical treatment. Morphological response is a useful decision-making tool for evaluating these patients for rescue liver resection following chemotherapy.

Background: Incidence and clinical characteristics of synchronous colorectal cancer (sCRC) patients significantly vary among studies, likely due to differences in surveillance methodology. If remain undetected, sCRC can progress to more advanced stages seriously aggravating patient prognosis. We studied the incidence and clinicopathological characteristics of Japanese patients with sCRCs who underwent surgery for primary CRC and received exhaustive perioperative surveillance. Methods: We recruited 1005 patients with surgically resected CRCs between January 2007 and December 2011. The associations of clinical and pathological factors with sCRC development were assessed by univariate and multivariate logistic regression. Results: Eighty-four patients (8.4 %) developed sCRCs, 16 of them(19.0 %) harboring three or more cancers. Companion sCRCs were smaller and earlier stage than the index lesion (P < 0.0001). In multivariate analysis, advanced age (odds ratio (OR) 1.03 per year; P = 0.009) and left colon tumor location (OR 1.78; P = 0.013) are associated with higher risk of sCRCs, particularly in females. Overall survival did not differ between solitary CRC and sCRC (P = 0.62). Conclusions: Our results highlight the importance of perioperative colonoscopy examination to ensure the absence of sCRCs that, being small and early staged, are more difficult to detect. The incidence of sCRC, and notably of triple or more sCRCs, was higher than previously recognized. Because they are also significantly higher than expected by merely stochastic accumulation of individual cancerous lesions, we suggest that the occurrence of many sCRC reflects a hitherto uncharacterized predisposition condition.

Although epithelial-mesenchymal transition (EMT) has been implicated as the pivotal event in metastasis, there is insufficient evidence related to EMT in clinical settings. Intratumor heterogeneity may lead to underestimation of gene expression representing EMT. In the present study, we investigated the expression of EMT-associated genes and microRNAs in primary colorectal cancer while considering intratumor heterogeneity. One-hundred and thirty-three multiple spatially separated samples were obtained from 8 patients with metastatic colorectal cancers and 8 with non-metastatic colorectal cancers, from the tumor center (TC), invasive front (IF) and metastasis. Differences in gene and microRNA expression were investigated by microarray and quantitative reverse-transcription PCR. Gene expression microarray analysis detected 7920 sites showing differing levels of gene expression among the TC, IF and metastasis. Expression of the EMT-associated gene zinc-finger E-box-binding homeobox 1 (ZEB1) significantly increased in the IF (P<0.01). To exclude individual differences, the expression ratio between TC and IF in each tumor was applied to analysis. This approach enabled recognition of the activation of the VEGF and Wnt signaling pathways, which were involved in metastasis via promotion of EMT. While no activation of these pathways was seen at the TC, regardless of whether tumors were metastatic or non-metastatic, they were preferentially activated at the IF in metastatic tumors, where high ZEB1 expression was seen in connection with decreased miR-200c expression. Multiple sampling in a tumor revealed that heterogeneous ZEB1 expression induced by EMT-associated signaling pathways played a pivotal role in metastasis via regulation of miR-200c.