野田 弘志

PURPOSE: Midline abdominal incisions (MAIs) are widely used in both open and minimally invasive surgery. Incisional hernia (IH) accounts for most long-term postoperative wound complications. This study explored the risk factors for IH due to MAI in patients with clean-contaminated wounds after elective gastroenterological surgery. METHODS: The present study targeted patients enrolled in 2 randomized controlled trials to evaluate the efficacy of intraoperative interventions for incisional SSI prevention after gastroenterological surgery for clean-contaminated wounds. The patients were reassessed, and pre- and intraoperative variables and postoperative outcomes were collected. IH was defined as any abdominal wall gap, regardless of bulge, in the area of a postoperative scar that was perceptible or palpable on clinical examination or computed tomography according to the European Hernia Society guidelines. The risk factors for IH were identified using univariate and multivariate analyses. RESULTS: The study population included 1,281 patients, of whom 273 (21.3%) developed IH. Seventy-four (5.8%) patients developed incisional SSI. Multivariate logistic regression analysis revealed that female sex (odds ratio [OR], 1.39; 95% confidence interval [CI] 1.03-1.86, p = 0.031), high preoperative body mass index (OR, 1.81; 95% CI 1.19-2.77, p = 0.006), incisional SSI (OR, 2.29; 95% CI 1.34-3.93, p = 0.003), and postoperative body weight increase (OR, 1.49; 95% CI 1.09-2.04, p = 0.012) were independent risk factors for IH due to MAI in patients who underwent elective gastroenterological surgery. CONCLUSION: We identified postoperative body weight increase at one year as a novel risk factor for IH in patients with MAI after elective gastroenterological surgery.

BACKGROUND: Clean-contaminated wounds should be the main target for reducing the burden of harm caused by surgical site infection after gastroenterological surgery. METHODS: The present study targeted 1,973 patients enrolled in 2 randomized controlled trials to evaluate the efficacy of intraoperative interventions for incisional surgical site infection prevention after gastroenterological surgery with clean-contaminated wounds. Patients were reassessed, and preoperative and postoperative variables were collected. Risk factors for surgical site infection were identified by univariate and multivariate analyses. RESULTS: The study population included 1,878 patients, among whom 213 (11.3%) developed overall surgical site infection and 119 (6.3%) developed incisional surgical site infection. A multivariate analysis revealed that steroid or immunosuppressant use (odds ratio 3.03; 95% confidence interval 1.37-6.73, P = .0064), open surgery (odds ratio 1.77; 95% confidence interval 1.11-2.83, P = .0167), and long operative time (odds ratio 2.31; 95% confidence interval 1.5-3.56, P < .001) were independent risk factors for incisional surgical site infection. Steroid or immunosuppressant use (odds ratio 2.62; 95% confidence interval 1.29-5.33, P = .0078), open surgery (odds ratio 2.13; 95% confidence interval 1.44-3.16, P < .001), and long operative time (odds ratio 2.92; 95% confidence interval 2.08-4.10, P < .001) were also independent risk factors for overall surgical site infection in the multivariate analysis. Furthermore, a multivariate analysis revealed that a long operative time (odds ratio 3.21; 95% confidence interval 1.69-6.1, P = .00378) was an independent risk factor for incisional surgical site infection in patients who underwent laparoscopic surgery. CONCLUSION: Even under current measures for surgical site infection prevention, surgeons should continue to make efforts to appropriately expand the indication of laparoscopic surgery and to reduce operative times even when performing laparoscopic surgery.

BACKGROUND/PURPOSE: Patients who receive preoperative biliary drainage (PBD) and biliary reconstruction are most at risk for incisional surgical site infection (SSI) in major hepatobiliary-pancreatic (HBP) surgery. METHODS: We evaluated 72 patients with PBD who underwent major HBP surgery and received intraoperative wound irrigation (IOWI) with saline and standard sutures between March 2014 and March 2017 (Cohort 1) and 63 patients with PBD who underwent major HBP surgery and received IOWI with aqueous 10% povidone-iodine and antibacterial sutures between June 2019 and February 2022 (Cohort 2). We compared the incidence of incisional SSI between the two cohorts. RESULTS: Twenty-seven (20.0%) of 135 patients developed incisional SSIs. The rate of current smoking was more frequent in patients who developed incisional SSIs than in those who did not (37.0% vs. 14.8%, p = .012). A total of 18 (25%) of 72 patients developed incisional SSI in Cohort 1, and nine (14.3%) of 63 developed incisional SSI in Cohort 2. Cohort 2 had a 10% lower incidence of incisional SSI than Cohort 1, a nonsignificant difference (p = .09). CONCLUSION: The implementation of IOWI with aqueous 10% PVP-I and antibacterial sutures failed to significantly reduce the incidence of incisional SSI in comparison to IOWI with saline and standard sutures in major HBP surgery.

OBJECTIVE: This trial evaluated the superiority of intraoperative wound irrigation (IOWI) with aqueous povidone-iodine (PVP-I) compared to that with saline for reducing the incidence of surgical site infection (SSI). BACKGROUND: IOWI with aqueous PVP-I is recommended for the prevention of SSI by the World Health Organization and Centers for Disease Control and Prevention, although the evidence level is low. METHODS: This single-institute in Japan, prospective, randomized, blinded-endpoint trial was conducted to assess the superiority of IOWI with aqueous PVP-I in comparison to IOWI with saline for reducing the incidence of SSI in clean-contaminated wounds after gastroenterological surgery. Patients ≥20 years old were assessed for eligibility, and eligible participants were randomized at a 1:1 ratio using a computer-generated block randomization. In the study group, IOWI was performed for one minute with 40 mL of aqueous 10% PVP-I before skin closure. In the control group, the procedure was performed with 100 mL of saline. Participants, assessors, and analysts were masked to the treatment allocation. The primary outcome was the incidence of incisional SSI in the intention-to-treat set. RESULTS: Between June 2019 and March 2022, 941 patients were randomized to the study group (473 patients) or the control group (468 patients). The incidence of incisional SSI was 7.6% in the study group and 5.1% in the control group (risk difference 0.025, 95% CI -0.006 to 0.056; risk ratio 1.484, 95% CI 0.9 to 2.448; P =0.154). CONCLUSION: The current recommendation of IOWI with aqueous PVP-I should be reconsidered.

INTRODUCTION: Surgical site infection (SSI) is one of the most common complications after gastrointestinal surgery, with a reported incidence of approximately 10%-25%, which is higher than the rates after other types of surgery. Intraoperative wound irrigation (IOWI) is a simple intervention for SSI prevention, and recent studies have reported that IOWI with aqueous povidone-iodine (PVP-I) is significantly more effective at reducing the incidence of SSI than saline. However, the evidence level of previous trials evaluating the efficacy of aqueous PVP-I solution for preventing SSI has been low. METHODS AND ANALYSES: We propose a single-institute, prospective, randomised, blinded-endpoint trial to assess the superiority of IOWI with aqueous 10% PVP-I solution compared with normal saline for reducing SSI in clean-contaminated wounds after elective gastrointestinal surgery. In the study group, IOWI with 40 mL of aqueous 10% PVP-I solution is performed for 1 min before skin suture, and in the control group, IOWI with 100 mL of saline is performed for 1 min before skin suture. We hypothesise that IOWI with aqueous 10% PVP-I solution will achieve a 50% reduction in the incidence of SSIs. The target number of cases is set at 950. The primary outcome is the incidence of incisional SSI up to postoperative day 30 and will be analysed in the modified intention-to-treat set. ETHICS AND DISSEMINATION: This trial was designed and is being conducted by Saitama Medical Center, Jichi Medical University, with approval from the Bioethics Committee for Clinical Research, Saitama Medical Center, Jichi Medical University. Participant recruitment began in June 2019. The final results will be reported in international peer-reviewed journals immediately after trial completion. TRIAL REGISTRATION NUMBER: UMIN000036889.

INTRODUCTION: The drain output volume (DOV) after pancreaticoduodenectomy (PD) is an easily assessable indicator in clinical settings. We explored the utility of the DOV as a possible warning sign of complications after PD. METHODS: A total of 404 patients undergoing PD were considered for inclusion. The predictability of the DOV for overall morbidity, major complications, intraabdominal infection (IAI), clinically relevant (CR) postoperative pancreatic fistula (POPF), CR delayed gastric emptying (DGE), CR chyle leak (CL), and CR post-pancreatectomy hemorrhaging (PPH) was evaluated. RESULTS: One hundred (24.8%) patients developed major complications, and 131 (32.4%) developed IAI. Regarding CR post-pancreatectomy complications, 75 (18.6%) patients developed CR-POPF, 23 (5.7%) developed CR-DGE, 20 (5.0%) developed CR-CL, and 28 (6.9%) developed CR-PPH. The median DOV on postoperative day (POD) 1 and POD 3 was 266 and 234.5 ml, respectively. A low DOV on POD 1 was an independent predictor of CR-POPF, and a high DOV on POD 3 was an independent predictor of CR-CL. A receiver operating characteristics (ROC) analysis revealed that the DOV on POD 1 had a negative predictive value (area under the curve [AUC] 0.655, sensitivity 65.0%, specificity 65.3%, 95% confidence interval [CI]: 0.587-0.724), with a calculated optimal cut-off value of 227 ml. An ROC analysis also revealed that the DOV on POD 3 had a positive predictive value (AUC 0.753, sensitivity 70.1%, specificity 75.0%, 95% CI: 0.651-0.856), with a calculated optimal cut-off value of 332 ml. CONCLUSION: A low DOV on POD 1 might be a postoperative warning sign for CR-POPF, similar to high drain amylase (DA) on POD 1, high DA on POD 3, and high CRP on POD 3. When the DOV on POD 1 after PD was low, surgeons should evaluate the reasons of a low DOV. A high DOV on POD 3 was a postoperative warning sign CR-CL, and might require an appropriate management of protein loss.

BACKGROUND: We investigated the risk factors for clinically relevant postoperative pancreatic fistula after pancreaticoduodenectomy in patients with a nondilated main pancreatic duct. METHODS: We investigated a total of 354 patients who underwent pancreaticoduodenectomy. The diameter of the main pancreatic duct, the shortest distance from the body surface to the pancreas (the pancreatic depth), and the computed tomography attenuation index (the difference between the pancreatic and splenic computed tomography attenuation) were measured in preoperative computed tomography. RESULTS: One hundred eighty-one (51.1%) patients had a nondilated main pancreatic duct, and 50 (27.6%) of the 181 patients with a nondilated main pancreatic duct developed a clinically relevant postoperative pancreatic fistula. Univariate analyses revealed that the calculated body mass index (≥21.8 kg/m2) (P = .004), deep pancreas (pancreatic depth ≥51.2 mm) (P = .001), and low computed tomography attenuation index (≤-3.8 Hounsfield units) (P = .02) were significant risk factors for clinically relevant postoperative pancreatic fistula. The multivariate logistic regression analysis revealed that deep pancreas (odds ratio 2.370; 95% confidence interval 1.0019-5.590; P = .049) was an independent risk factor for clinically relevant postoperative pancreatic fistula. Among patients with a nondilated main pancreatic duct, deep pancreas (in comparison to patients without deep pancreas) was associated with male sex (72.7% vs 54.9%; P = .016), higher body mass index (22.5 kg/m2 vs 19.6 kg/m2; P < .001), a history of diabetes mellitus (24.5% vs 8.5%; P = .006), a lower computed tomography attenuation index (-9.6 Hounsfield units vs -4.6 Hounsfield units; P = .007), a longer operative time (454 minutes vs 420 minutes; P = .007), and a higher volume of intraoperative blood loss (723 mL vs 500 mL; P < .001), respectively. CONCLUSION: Deep pancreas may be an important parameter associated with significant risk factors for clinically relevant postoperative pancreatic fistula after pancreaticoduodenectomy in patients with a nondilated main pancreatic duct.

BACKGROUND: /Objectives: The objectives of this study were to identify the factors affecting patients' survival and the characteristics of five-year survivors of pancreatic ductal adenocarcinoma (PDAC) after pancreatectomy as well as to clarify the correlation between the development of postoperative complications and a five-year survival. METHODS: A total of 104 patients underwent pancreatectomy for PDAC between April 2005 and March 2013 with curative intent. Patients who survived for more than five years after pancreatectomy were classified as long-term survivors. Sixteen demographic and clinical variables and 10 pathological variables were comprehensively assessed for their associations with the patients' survival time and long-term survival. RESULTS: The presence of preoperative comorbidity (OR: 1.65, 95% CI 1.02-2.67, p = 0.042), postoperative overall complications (OR: 1.78, 95% CI 1.03-3.10, p = 0.041), a lymph node positivity ratio of ≥0.2 (OR: 3.04, 95% CI 1.51-6.11, p = 0.002), and portal invasion (OR: 2.58, 95% CI 1.48-4.49, p = 0.001) were identified as independent factors affecting the patients' survival. The absence of postoperative overall complications was identified as an independent factor related to long-term survival in the multivariate analysis (OR: 0.08, 95% CI 0.01-0.82, p = 0.034). CONCLUSIONS: The presence of preoperative comorbidity, postoperative overall complications, LNR ≥0.2, and portal invasion were prognostic factors affecting the patients' survival, and avoiding postoperative complications after pancreatectomy might contribute to the long-term survival of PDAC patients after pancreatectomy. The further improvement of surgical procedures and perioperative care in order to reduce the rate of postoperative complications should be attempted.

BACKGROUND/OBJECTIVES: The aims of this study were to clarify the effect of preoperative biliary drainage (PBD) on postoperative outcomes and the role of preoperative intentional exchange from endoscopic nasobiliary drainage (ENBD) to endoscopic retrograde biliary drainage (ERBD) for patients waiting to undergo pancreaticoduodenectomy (PD). METHODS: We evaluated the effect of PBD and intentional exchange of PBD on the perioperative variables in 292 patients. RESULTS: A total of 179 (61.3%) of 292 patients received PBD. There was no marked difference in the postoperative outcomes between the patients who did and did not receive PBD. Among the 160 patients who initially received endoscopic PBD, 10 (6.3%) underwent stent exchange for stent dysfunction, 59 (36.9%) who did not develop stent dysfunction underwent intentional stent exchange from ENBD to ERBD (bridge PBD group), and 91 (56.9%) did not receive any stent exchange (unchanged PBD group). The bridge PBD group had a longer duration of PBD (37 days) (p < 0.001) and a shorter preoperative hospital stay after PBD (32 days) (p < 0.001) than the unchanged PBD group (25 and 46 days, respectively); however, there were no significant differences in the postoperative variables. The incidence of stent exchange due to stent dysfunction in the bridge PBD group (11.9%) was lower than that in patients who initially received ERBD (36.0%) (p = 0.015). CONCLUSIONS: Bridge PBD worked well for extending the duration of PBD without worsening the postoperative outcomes after PD.

Pancreatectomy might confer a survival benefit in patients with metastatic tumors of the pancreas (MTPs); however, the optimal treatment for MTP has not been established. We reviewed six patients with MTP undergoing pancreatectomy and discussed the clinical features, surgical treatment, and survival. The sites of primary cancer included renal cell carcinoma (RCC) (n = 5; 83.3%) and rectal cancer (n = 1; 16.7%). The median interval between the resection of the primary site and the development of MTP was 157 months (range, 16-180 months). Three (60.0%) of the five cases of MTP-originating RCC and a MTP-originating rectal cancer, biopsy was performed under endoscopic ultrasonography guidance and MTP was pathologically diagnosed. All patients with MTP originating from RCC have remained alive for 3, 13, 18, 18, and 113 months without recurrence after pancreatectomy. In contrast, the patient with MTP originating from rectal cancer developed multiple liver metastases at 7 months after pancreatectomy, and then underwent chemotherapy. A preoperative pathological diagnosis using biopsy under endoscopic ultrasonography guidance was indispensable for the treatment of MTP. Pancreatectomy for MTP conferred a survival benefit in patients with metastatic RCC, whereas a combination of pancreatectomy and chemotherapy might be necessary to improve the prognosis of patients with metastatic colorectal cancer.

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.

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.

Background/Aims: Intra-abdominal infection (IAI) after pancreaticoduodenectomy (PD) is a common cause of prolongation of postoperative hospital stay and readmission to the hospital following discharge. Methodology: Two hundred and six patients undergoing PD were reviewed to investigate the risk factors for IAI after PD. Patients were separated into two groups: those who developed IAI after PD (Group A; n=44), and those who had not developed IAI after PD (Group B; n=162), the two groups were then compared to identify the risk factors for IAI after PD. A hundred and six patients (51.5%) underwent preoperative biliary drainage (PBD). Results: Multivariate analysis revealed that pancreatic fistula (PF) was an independent risk factor for IAI after PD (p&lt;0.001; odds ratio=9.58; 95% confidence interval=4.37-21.0), but PBD was not a significant risk factor. Conclusions: We demonstrated that the adequate PBD might not affect IAI after PD. On the other hand, PF was an independent risk factor for IAI after PD. A large randomized controlled trial, which would prove the effect of early removal of a prophylactic placed drain to prevent IAI, should be planned.

Recent studies have suggested that epigenetic inactivation of tumour-related genes by promoter methylation participates in the development of gastric cancer. We newly identified the frequently aberrant promoter methylation of alpha-1B-adrenergic receptor (ADRA1B) in colorectal cancer by methylation-sensitive representational difference analysis (MS-RDA) and examined the methylation status of the ADRA1B promoter in 34 paired samples of colorectal cancer and surrounding epithelial tissue, and 34 paired samples of gastric cancer and surrounding epithelial tissue. In colorectal cancers, only four of 34 (11.8%) tumours showed ADRA1B promoter methylation. In contrast, ADRA1B promoter methylation was detected in 24 of 34 (70.6%) gastric cancers and in 14 of 34 (41.2%) surrounding epithelial tissues. The frequency of ADRA1B promoter methylation was higher in gastric epithelial tissues with intestinal metaplasia (41.6%) than in those without intestinal metaplasia (25.0%). Reverse transcription-PCR detected reduced ADRA1B expression in 12 of 18 (66.7%) gastric cancers, and its promoter methylation was detected in 11 of these 12 (91.7%) gastric cancers with reduced ADRA1B expression. Thus, ADRA1B promoter is frequently methylated in gastric cancer. Our results suggest that the ADRA1B gene is an important tumour-related gene frequently involved in the development and progression of gastric cancer.

The development of colorectal neoplasms proceeds mainly via the adenoma-carcinoma sequence. BRAF and RASSF1A are members of Ras-signaling pathways, but the roles of their aberrations in colorectal carcinogenesis remain unclear. The authors studied mutations of the BRAF and K-ras genes, RASSF1A promoter methylation, and p53 overexpression in 43 polypoid-type and 30 flat-type early-stage colorectal cancers. No tumor simultaneously showed any combination of K-ras mutations, BRAF mutations, and RASSF1A promoter methylation. Three of the 73 tumors (4.1%) had BRAF mutations. All BRAF mutation-positive tumors were flat-type cancers, not associated with coexisting adenoma or p53 overexpression. RASSF1A promoter methylation was detected in 12 out of 73 tumors (16.4%), and the proportion of positive cases was similar in polypoid-type and flat-type cancers. BRAF mutations, K-ras mutations, and RASSF1A promoter methylation independently participate in early-stage colorectal carcinogenesis. BRAF mutations are involved only in flat-type cancers, whereas RASSF1A promoter methylation is involved in both polypoid-type and flat-type cancers. Thus, BRAF mutations most likely participate in de novo colorectal carcinogenesis, K-ras mutations in the adenoma-carcinoma sequence of colorectal carcinogenesis, and RASSF1A promoter methylation in both cascades.

BACKGROUND. The growth pattern of early gastric carcinoma, as based on a volumetric analysis, reflects the biologic characteristics of a tumor. The penetrating growth (Pen) type tumor has an unfavorable prognosis, compared with the case of a superficially spreading (Super) type. The wild-type of the p53 protein plays an important role in cell growth regulation and apoptosis. The p21 protein, which is encoded by the WAF1/CIP1 gene, is a downstream target effector of wild-type p53 protein, and these proteins act as tumor suppressors in a negative cell-cycle regulation. METHODS. In 133 Japanese patients with early gastric carcinoma with submucosal invasion, expressions of p53 and p21 proteins were studied immunohistochemically, and the relation between growth pattern and expressions was analyzed. RESULTS. Early gastric carcinomas were grouped into the superficially spreading (Super) type 40 (30.1%) cases, expansively penetrating growth (Pen-A) type 28 (21.1%), infiltratively penetrating growth (Pen-B) type 20 (15.0%), small mucosal type 35 (26.3%), and mixed type 10 (7.5%). The Pen-A type tumors were characterized by the highest incidence of p53 expression and loss of p21 expression, and the rate of p53-positive and/or p21-negative cases was 71.4%. There were significant differences in the incidence of the p53 expression (50.0% vs. 25.0%), the loss of p21 expression (53.6% vs. 27.5%), and the 5-year survival rate (83.2% vs. 97.2%) between the Pen-A type and the Super type. CONCLUSIONS. Thus, deregulation of the cell cycle by p53 and p21 in this study was shown to play an important role in progression of Pen-A type early gastric carcinoma. (C) 2001 American Cancer Society.