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The Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS) nomogram was developed to predict disease-free survival in patients with colorectal liver metastases (CRLM) undergoing upfront hepatectomy. However, the utility of the nomogram in patients with resected CRLM remains unknown in the current situation in which treatment strategies are changing with advances in drugs.Patients in the initial nomogram cohort (n = 727) and validation cohort (n = 2225) were divided into the upfront hepatectomy and preoperative chemotherapy groups. The nomogram was validated by measuring calibration and discrimination in the two cohorts. Calibration curves were plotted, and survival probabilities were compared. Finally, to quantify the discrimination power, we estimated the concordance index (C-index).In the upfront hepatectomy group, the C-index was 0.63, the suitable cutoff value of the Beppu score was 7, and adjuvant chemotherapy was significantly effective limited to high-risk patients (Beppu score ≥7). The C-index was 0.56 in the preoperative chemotherapy group.The JSHBPS nomogram remains beneficial for patients undergoing upfront hepatectomy in the recent era but is less effective for patients undergoing hepatectomy after chemotherapy. Patients with a Beppu score ≥7 showed high-risk recurrence, and adjuvant chemotherapy should be recommended for these patients.

Supplemental digital content is available in the text., Objective The combination of gemcitabine plus nab-paclitaxel (GnP) has not been studied in Japanese patients with resectable pancreatic cancer (PC). This study aimed to assess the tolerability of adjuvant GnP in Japanese patients with resected PC. Methods This was a Phase I, open-label, multicenter, single-arm study of patients with resected PC in Japan. Patients received 125 mg/m2 of nab-paclitaxel and 1000 mg/m2 of gemcitabine on days 1, 8, and 15 of a 28-day cycle for a total of 6 cycles. The primary end point was tolerability, defined as the absence of specific grade 3 or higher treatment-related adverse events by the end of cycle 2. Secondary end points included safety, disease-free survival, and overall survival. Results Forty-one patients were enrolled between June 2016 and February 2017 (median age, 68 years; 51% male; stage II, 95%). Gemcitabine plus nab-paclitaxel met the tolerability criteria in 39 of the 40 patients included in the tolerability analysis set (97.5%). The most common treatment-related adverse events were leukopenia, neutropenia, alopecia, and peripheral sensory neuropathy. After a follow-up of 30.1 months, median disease-free survival was 17.0 months and median overall survival was not reached. Conclusions These results show that adjuvant GnP is tolerable in Japanese patients with resected PC. Clinical Trial Registration No.: JapicCTI-163179

Objective: to reach global expert consensus on the definition of TOLS in minimally invasive and open liver resection among renowned international expert liver surgeons using a modified Delphi method.Summary background data: textbook outcome is a novel composite measure combining the most desirable postoperative outcomes into one single measure and representing the ideal postoperative course. Despite a recently developed international definition of Textbook Outcome in Liver Surgery (TOLS), a standardized and expert consensus-based definition is lacking.Methods: this international, consensus-based, qualitative study used a Delphi process to achieve consensus on the definition of TOLS. The survey comprised 6 surgical domains with a total of 26 questions on individual surgical outcome variables. The process included 4 rounds of online questionnaires. Consensus was achieved when a threshold of at least 80% agreement was reached. Results from the Delphi rounds were used to establish an international definition of TOLS.Results: in total, 44 expert liver surgeons from 22 countries and all three major international hepato-pancreato-biliary associations completed round 1. Forty-two (96%), 41 (98%) and 41 (98%) of the experts participated in round 2, 3 and 4, respectively. The TOLS definition derived from the consensus process included the absence of intraoperative grade ≥2 incidents, postoperative bile leakage grade B/C, postoperative liver failure grade B/C, 90-day major postoperative complications, 90-day readmission due to surgery-related major complications, 90-day/in-hospital mortality and the presence of R0 resection margin.Conclusions: this is the first study providing an international expert consensus-based definition of TOLS for minimally invasive and open liver resections by use of a formal Delphi consensus approach. TOLS may be useful in assessing patient-level hospital performance and carrying out international comparisons between centers with different clinical practices to further improve patient outcomes.

Although pancreatic cancer (PC) has an extremely poor prognosis, the 5-year survival rate of patients with pancreatic high-grade precancerous lesion without invasive carcinoma (PHP) is favorable. PHP diagnosis and identification of patients requiring intervention are needed. We aimed to validate a modified PC detection scoring system regarding its detection ability for PHP and PC in the general population.We modified an existing PC detection scoring system that incorporates low-grade risk (LGR) factors (family history, presence of diabetes mellitus [DM] or worsening DM, heavy drinking, smoking, stomach symptoms, weight loss, and pancreatic enzyme) and high-grade risk (HGR) factors (new-onset DM, familial PC, jaundice, tumor biomarkers, chronic pancreatitis, intraductal papillary mucinous neoplasm, cysts, hereditary PC syndrome, and hereditary pancreatitis). Each factor was scored as one point; LGR score ≥3 points and/or HGR score ≥1 point (positive scores) were indicative of PC. The newly modified scoring system incorporated main pancreatic duct dilation as an HGR factor. The PHP diagnosis rate using this scoring system combined with EUS was prospectively analyzed.Among 544 patients with positive scores, 10 had PHP. The diagnosis rates were 1.8% for PHP and 4.2% for invasive PC. Although the number of LGR and HGR factors tended to increase with PC progression, none of the individual factors were significantly different between patients with PHP and those without lesions.The newly modified scoring system evaluating multiple factors associated with PC could potentially identify patients with higher risk of PHP or PC.

Objective: Morphological subtyping of intraductal papillary mucinous neoplasms of the pancreas (IPMNs) into pancreatobiliary-type, intestinal-type, or gastric-type is a prognostic factor, however, molecular foundations explaining the difference of clinical behaviors are unknown. Our research aimed to elucidate the molecular phenotypes associated with subtypes of IPMNs and establish a risk stratification model. Design: In 171 IPMNs with high-grade dysplasia (HGD) and invasive carcinoma, we analyzed protein expressions of p16, p53, SMAD4, STK11, and β-catenin by immunohistochemistry, and mutations and copy number variations of KRAS and GNAS by droplet digital PCR, and analyzed the association with clinicopathological factors. Results: In HGD components of IPMNs of pancreatobiliary- (n=66), intestinal- (n=70), and gastric-type (n=35), alterations were detected respectively as follows: KRAS mutation; 98%, 62%, and 83% (P Citation Format: Yuko Omori, Yusuke Ono, Takashi Kokumai, Fumiko Date, Ryota Higuchi, Goro Honda, Yusuke Mizukami, Takanori Morikawa, Michiaki Unno, Toru Furukawa. Molecular phenotyping and risk stratification of intraductal papillary mucinous neoplasms [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr A081.

The prognosis of pancreatic ductal carcinoma (PDAC) with peritoneal metastasis remains dismal. Systemic chemotherapy alone may not be effective, and the combination of intraperitoneal chemotherapy with systemic chemotherapy is expected to prolong the overall survival in patients with peritoneal metastasis. We have designed a randomized phase III trial to confirm the superiority of intravenous (i.v.) and intraperitoneal (i.p.) paclitaxel (PTX) with S-1 relative to gemcitabine plus nab-PTX (GnP), which is the current standard therapy for patients with metastatic PDAC. A total of 180 patients will be accrued from 30 institutions within 3 years. Patients will be randomly assigned in a 1:1 ratio to receive either i.v. and i.p. PTX with S-1 or GnP (target of 90 patients per group). The primary endpoint is overall survival; secondary endpoints are progression-free survival, response rate, proportion with negative peritoneal washing cytology during chemotherapy, proportion requiring conversion surgery, and adverse event profiles. Japan Registry of Clinical Trials jRCTs051180199 (https://jrct.niph.go.jp/).

To improve the poor prognosis of pancreatic ductal adenocarcinoma (PDAC), the diagnosis of early-stage PDAC is essential. In particular, the diagnosis of high-grade intraepithelial pancreatic neoplasia/carcinoma in situ (HG-PanIN/CIS) is the best option. However, it is almost impossible to directly observe HG-PanIN/CIS. Thus, identifying a secondary imaging finding due to the disorder is important. Focal pancreatic parenchymal atrophy (FPPA) and hypoechoic area have been reported as preferred secondary signs. We studied 50 patients to clarify the effectiveness of FPPA in diagnosing HG-PanIN/CIS. Most patients had the opportunity to undergo further examination due to the presence of a cyst. Among the 50 patients, 23 (46%) had positive results for serial pancreatic-juice aspiration cytologic examination (SPACE), which has high sensitivity and specificity for diagnosing PADC; 20 of the 23 (87.0%) patients underwent surgery to resect the pancreatic part including the FPPA. Distal pancreatectomy and pancreatoduodenectomy were performed in 19 patients and one patient, respectively. In 13 of the 20 (65%) patients, histopathological examination revealed HG-PanIN/CIS in the pancreatic ductal epithelium of the resected specimens. FPPA could indicate HG-PanIN/CIS, but not satisfactorily. One of the factors for the unsatisfactory results might be the difficulty in identifying FPPA in the pancreatic head area. On the other hand, a pancreatic cyst, especially in the area of FPPA, could lead to the diagnosis of HG-PanIN/CIS. The size of the cyst does not affect the diagnosis of HG-PanIN/CIS.

Background To explore best practices for acute cholecystitis, it is necessary to construct a system to assess the difficulty of laparoscopic cholecystectomy (LC) based on intraoperative findings. In this study, multiple evaluators assessed videos of LC to assemble a library of typical video clips for 25 intraoperative findings. Methods We have previously identified 25 items that contribute to surgical difficulty in LC. For each item, roughly 30-second video clips were submitted from videos of LC performed at member institutions. We then selected one typical video from the collected clips based on simple tabulation of the instances of agreement. Inter-rater agreement was assessed with Fleiss's κ and Gwet's agreement coefficient (AC). Results Except in the case of two assessment items ("edematous change" and "easy bleeding"), κ or AC significantly exceeded 0.5 and the typical videos were judged to be applicable. For the two remaining items, the evaluation was repeated after clarifying the definitions of positive and negative findings. Eventually, they were recognized as typical. The completed video clip library contains 31 clips and is divided into five categories (http://www.jshbps.jp/modules/project/index.php?content_id=13). Conclusions This clip library may be highly useful in clinical settings as a more objective standard for assessing surgical difficulty in LC.

Background/purpose The purpose of the present study was to assess long-term outcomes following liver resection for colorectal liver metastases (CRLM) with concurrent extrahepatic disease and to identify the preoperative prognostic factors for selection of operative candidates. Methods In this retrospective, multi-institutional study, 3820 patients diagnosed with CRLM during 2005-2007 were identified using nationwide survey data. Data of identified patients with concurrent extrahepatic lesions were analyzed to estimate the impact of liver resection on overall survival (OS) and to identify preoperative, prognostic indicators. Results Three- and 5-year OS rates after liver resection in 251 CRLM patients with extrahepatic disease (lung, n = 116; lymph node, n = 51; peritoneal, n = 37; multiple sites, n = 23) were 50.2% and 32.0%, respectively. Multivariate analysis revealed that a primary tumor in the right colon, lymph node metastasis from the primary tumor, serum carbohydrate antigen (CA) 19-9 level >37 UI/mL, the site of extrahepatic disease, and residual liver tumor after hepatectomy were associated with higher mortality. We proposed a preoperative risk scoring system based on these factors that adequately discriminated 5-year OS after liver resection in training and validation datasets. Conclusions Performing R0 liver resection for colorectal liver metastases with treatable extrahepatic disease may prolong survival. Our proposed scoring system may help select appropriate candidates for liver resection.

Since the beginning of laparoscopic liver surgery, resection of the posterosuperior segments has been considered one of the most challenging procedure due to its difficult access. The main drawbacks of the laparoscopic approach to dome lesions are poor visualization, the difficulty of instrumentation and the greater complexity in the control of bleeding. In the evolution of minimally invasive techniques from hybrid techniques to the current purely laparoscopic approaches, the different authors have established gradually the currents indications and surgical techniques to operate these segments with a similar feasibility and safety than open approach. The standardization in the patient position, the use of intercostal trocars, the learning curve in laparoscopic liver surgery, the management of the hepatic blood flow and the refinement of the technique in the extrahepatic and intrahepatic Glissonean pedicle approaches, has allowed to leave behind the initial contraindications about the laparoscopic approach in these segments. In the present review of the literature, the accumulated experience of the different groups in minimally invasive liver surgery together with the technological advances in the different laparoscopic devices have facilitated the resection of tumors in segments 7 and 8 with similar and even better results than open surgery.

Most models for predicting malignant pancreatic intraductal papillary mucinous neoplasms were developed based on logistic regression (LR) analysis. Our study aimed to develop risk prediction models using machine learning (ML) and LR techniques and compare their performances. This was a multinational, multi-institutional, retrospective study. Clinical variables including age, sex, main duct diameter, cyst size, mural nodule, and tumour location were factors considered for model development (MD). After the division into a MD set and a test set (2:1), the best ML and LR models were developed by training with the MD set using a tenfold cross validation. The test area under the receiver operating curves (AUCs) of the two models were calculated using an independent test set. A total of 3,708 patients were included. The stacked ensemble algorithm in the ML model and variable combinations containing all variables in the LR model were the most chosen during 200 repetitions. After 200 repetitions, the mean AUCs of the ML and LR models were comparable (0.725 vs. 0.725). The performances of the ML and LR models were comparable. The LR model was more practical than ML counterpart, because of its convenience in clinical use and simple interpretability.

text, 紀要論文 / Departmental Bulletin Paper

text, 紀要論文/Departmental Bulletin Paper

The initial management of patients with suspected acute biliary infection starts with the measurement of vital signs to assess whether or not the situation is urgent. If the case is judged to be urgent, initial medical treatment should be started immediately including respiratory/circulatory management if required, without waiting for a definitive diagnosis. The patient's medical history is then taken; an abdominal examination is performed; blood tests, urinalysis, and diagnostic imaging are carried out; and a diagnosis is made using the diagnostic criteria for cholangitis/cholecystitis. Once the diagnosis has been confirmed, initial medical treatment should be started immediately, severity should be assessed according to the severity grading criteria for acute cholangitis/cholecystitis, and the patient's general status should be evaluated. For mild acute cholangitis, in most cases initial treatment including antibiotics is sufficient, and most patients do not require biliary drainage. However, biliary drainage should be considered if a patient does not respond to initial treatment. For moderate acute cholangitis, early endoscopic or percutaneous transhepatic biliary drainage is indicated. If the underlying etiology requires treatment, this should be provided after the patient's general condition has improved; endoscopic sphincterotomy and subsequent choledocholithotomy may be performed together with biliary drainage. For severe acute cholangitis, appropriate respiratory/circulatory management is required. Biliary drainage should be performed as soon as possible after the patient's general condition has been improved by initial treatment and respiratory/circulatory management. Free full articles and mobile app of TG18 are available at: http://www.jshbps.jp/modules/en/index.php?content_id=47. Related clinical questions and references are also included.

In some cases, laparoscopic cholecystectomy (LC) may be difficult to perform in patients with acute cholecystitis (AC) with severe inflammation and fibrosis. The Tokyo Guidelines 2018 (TG18) expand the indications for LC under difficult conditions for each level of severity of AC. As a result of expanding the indications for LC to treat AC, it is absolutely necessary to avoid any increase in bile duct injury (BDI), particularly vasculo-biliary injury (VBI), which is known to occur at a certain rate in LC. Since the Tokyo Guidelines 2013 (TG13), an attempt has been made to assess intraoperative findings as objective indicators of surgical difficulty; based on expert consensus on these difficulty indicators, bail-out procedures (including conversion to open cholecystectomy) have been indicated for cases in which LC for AC is difficult to perform. A bail-out procedure should be chosen if, when the Calot's triangle is appropriately retracted and used as a landmark, a critical view of safety (CVS) cannot be achieved because of the presence of nondissectable scarring or severe fibrosis. We propose standardized safe steps for LC to treat AC. To achieve a CVS, it is vital to dissect at a location above (on the ventral side of) the imaginary line connecting the base of the left medial section (Segment 4) and the roof of Rouviere's sulcus and to fulfill the three criteria of CVS before dividing any structures. Achieving a CVS prevents the misidentification of the cystic duct and the common bile duct, which are most commonly confused. Free full articles and mobile app of TG18 are available at: http://www.jshbps.jp/modules/en/index.php?content_id=47. Related clinical questions and references are also included.

Since the publication of the Tokyo Guidelines in 2007 and their revision in 2013, appropriate management for acute cholecystitis has been more clearly established. Since the last revision, several manuscripts, especially for alternative endoscopic techniques, have been reported; therefore, additional evaluation and refinement of the 2013 Guidelines is required. We describe a standard drainage method for surgically high-risk patients with acute cholecystitis and the latest developed endoscopic gallbladder drainage techniques described in the updated Tokyo Guidelines 2018 (TG18). Our study confirmed that percutaneous transhepatic gallbladder drainage should be considered the first alternative to surgical intervention in surgically high-risk patients with acute cholecystitis. Also, endoscopic transpapillary gallbladder drainage or endoscopic ultrasound-guided gallbladder drainage can be considered in high-volume institutes by skilled endoscopists. In the endoscopic transpapillary approach, either endoscopic naso-gallbladder drainage or gallbladder stenting can be considered for gallbladder drainage. We also introduce special techniques and the latest outcomes of endoscopic ultrasound-guided gallbladder drainage studies. Free full articles and mobile app of TG18 are available at: http://www.jshbps.jp/modules/en/index.php?content_id=47. Related clinical questions and references are also included.

Antimicrobial therapy is a mainstay of the management for patients with acute cholangitis and/or cholecystitis. The Tokyo Guidelines 2018 (TG18) provides recommendations for the appropriate use of antimicrobials for community-acquired and healthcare-associated infections. The listed agents are for empirical therapy provided before the infecting isolates are identified. Antimicrobial agents are listed by class-definitions and TG18 severity grade I, II, and III subcategorized by clinical settings. In the era of emerging and increasing antimicrobial resistance, monitoring and updating local antibiograms is underscored. Prudent antimicrobial usage and early de-escalation or termination of antimicrobial therapy are now important parts of decision-making. What is new in TG18 is that the duration of antimicrobial therapy for both acute cholangitis and cholecystitis is systematically reviewed. Prophylactic antimicrobial usage for elective endoscopic retrograde cholangiopancreatography is no longer recommended and the section was deleted in TG18. Free full articles and mobile app of TG18 are available at: http://www.jshbps.jp/modules/en/index.php?content_id=47. Related clinical questions and references are also included.

To collect big data for further research to improve treatment outcomes in patients with colorectal liver metastasis (CRLM), the Joint Committee for Nationwide Survey on CRLM was established by the Japanese Society for Cancer of the Colon and Rectum and the Japanese Society of Hepato-Biliary-Pancreatic Surgery. The joint committee initiated data collection since 2014. The data of 4,237 patients newly diagnosed with CRLM between 2005 and 2007 were registered from 134 departments of 127 institutions (64%) among 209 departments (from 201 institutions) that agreed to participate in this study. Finally, 3,820 patients were enrolled in this report after a quality management process by the joint committee. We report the comprehensive data obtained from 3,820 patients, clinicopathological findings, treatment strategies, prognoses, and implementation status of chemotherapy. The joint committee is prospectively collecting data of patients newly diagnosed with CRLM after 2013 and will provide these raw data, including data of patients diagnosed between 2005 and 2007, to researchers who will conduct meaningful studies that meet the aim of the joint committee.

Background Even though most patients who undergo resection of pancreatic adenocarcinoma have T3 disease with extra-pancreatic tumor extension, T3 disease is not currently classified by tumor size. The aim of this study was to modify the current TNM classification of pancreatic adenocarcinoma to reflect the influence of tumor size., Methods A total of 847 consecutive pancreatectomy patients were recruited from multiple centers. Optimum tumor size cutoff values were calculated by receiver operating characteristics analysis for tumors limited to the pancreas (T1/2) and for T3 tumors. In our modified TNM classification, stage II was divided into stages IIA (T3aN0M0), IIB (T3bN0M0), and IIC (T1-3bN1M0) using tumor size cutoff values. The usefulness of the new classification was compared with that of the current classification using Akaike’s information criterion (AIC)., Results The optimum tumor size cutoff value distinguishing T1 and T2 was 2 cm, while T3 was divided into T3a and T3b at a tumor size of 3 cm. The median survival time of the stages IIA, IIB, and IIC were 44.7, 27.6, and 20.3 months, respectively. There were significant differences of survival between stages IIA and IIB (P = 0.02) and between stages IIB and IIC (P = 0.03). The new classification showed better performance compared with the current classification based on the AIC value., Conclusions This proposed new TNM classification reflects the influence of tumor size in patients with extra-pancreatic tumor extension (T3 disease), and the classification is useful for predicting mortality.

OBJECTIVE: To evaluate the clinical efficacy and tolerability of intravenous (i.v.) and intraperitoneal (i.p.) paclitaxel combined with S-1, "an oral fluoropyrimidine derivative containing tegafur, gimestat, and otastat potassium" in chemotherapy-naive pancreatic ductal adenocarcinoma (PDAC) patients with peritoneal metastasis. BACKGROUND: PDAC patients with peritoneal metastasis (peritoneal deposits and/or positive peritoneal cytology) have an extremely poor prognosis. An effective treatment strategy remains elusive. METHODS: Paclitaxel was administered i.v. at 50 mg/m and i.p. at 20 mg/m on days 1 and 8. S-1 was administered at 80 mg/m/d for 14 consecutive days, followed by 7 days of rest. The primary endpoint was 1-year overall survival (OS) rate. The secondary endpoints were antitumor effect and safety (UMIN000009446). RESULTS: Thirty-three patients who were pathologically diagnosed with the presence of peritoneal dissemination (n = 22) and/or positive peritoneal cytology (n = 11) without other organ metastasis were enrolled. The tumor was located at the pancreatic head in 7 patients and the body/tail in 26 patients. The median survival time was 16.3 (11.47-22.57) months, and the 1-year survival rate was 62%. The response rate and disease control rate in assessable patients were 36% and 82%, respectively. OS in 8 patients who underwent conversion surgery was significantly higher than that of nonsurgical patients (n = 25, P = 0.0062). Grade 3/4 hematologic toxicities occurred in 42% of the patients and nonhematologic adverse events in 18%. One patient died of thrombosis in the superior mesenteric artery. CONCLUSIONS: This regimen has shown promising clinical efficacy with acceptable tolerability in chemotherapy-naive PDAC patients with peritoneal metastasis.

Background Generally, surgeons’ perceptions of surgical safety are based on experience and institutional policy. Our recent pilot survey demonstrated that the acceptable duration of surgery and criteria for open conversion during laparoscopic cholecystectomy (LC) vary among workplaces. Methods A web-based survey was distributed to 554 expert LC surgeons in Japan, Korea, and Taiwan. The questionnaire covered LC experience, safety measures and recognition of landmarks, decision-making regarding conversion to open/partial cholecystectomy and the implications of this decision. Overall responses were compared among nations, and then stratified by LC experience level (lifetime cases 200–499, 500–999, and ≥1000). Results The response rate was 92.6% (513/554); 67 surgeons with ≤199 LCs were excluded, and responses from 446 surgeons were analyzed. We observed significant differences among nations on almost all questions. Differences that remained after stratification by LC experience were on questions related to acceptable duration of surgery, adoption rates of intraoperative cholangiography, the “critical view of safety” technique, identification of Rouviere's sulcus, recognition of the SS-Inner layer theory, and intraoperative judgment to abandon conventional LC. Conclusions Even among experts, surgeons’ perceptions during LC are workplace-dependent. A novel grading system of surgical difficulty and standardized LC procedures are paramount to generate high-level evidence. This article is protected by copyright. All rights reserved.

BACKGROUND: Bile duct injury (BDI) during laparoscopic cholecystectomy remains a serious iatrogenic surgical complication. BDI most often occurs as a result of misidentification of the anatomy; however, clinical evidence on its precise mechanism and surgeons' perceptions is scarce.METHODS: Surgeons from Japan, Korea, Taiwan, and the U.S., etc. (n = 614) participated in a questionnaire regarding their BDI experience and near-misses; and perceptions on landmarks, intraoperative findings, and surgical techniques. Respondents voted for a Delphi process and graded each item on a five-point scale. The consensus was built when ≥80% of overall responses were 4 or 5.RESULTS: Response rates for the first- and the second-round Delphi were 60.6% and 74.9%, respectively. Misidentification of local anatomy accounted for 76.2% of BDI. Final consensus was reached on: 1) Effective retraction of the gallbladder, 2) Always obtaining critical view of safety, and 3) Avoiding excessive use of electrocautery/clipping as vital procedures; and 4) Calot's triangle area and 5) Critical view of safety as important landmarks. For 6) Impacted gallstone and 7) Severe fibrosis/scarring in Calot's triangle, bail-out procedures may be indicated.CONCLUSIONS: A consensus was reached among expert surgeons on relevant landmarks and intraoperative findings and appropriate surgical techniques to avoid BDI. This article is protected by copyright. All rights reserved.

High-grade pancreatic intraepithelial neoplasia (HG PanIN)/carcinoma in situ (CIS) in the pancreatic body and tail can induce parenchymal atrophy through chronic inflammatory changes presenting as a Hypoechoic area on EUS (Hypocho) or focal pancreatic parenchymal atrophy (FPPA) on computed tomography (CT) and magnetic resonance imaging (MRI). We herein discussed two patients with a hypoechoic area in the pancreatic head and neck on EUS resembling pancreatic ductal adenocarcinoma (PDAC). The lesions consisted of dense fibrosis and fat infiltration with pancreatic parenchymal atrophy around the HG PanIN/CIS in the main pancreatic duct (MPD), which penetrated the lesion and showed mild stenosis and upstream dilation. CT and MRI were unable to visualize the lesions. A specimen was obtained from one lesion by fine-needle aspiration under EUS (EUS-FNA) guidance for histopathological and cytological analysis, but the tests returned negative for adenocarcinoma. However, serial pancreatic-juice aspiration cytologic examination (SPACE) revealed adenocarcinoma in both lesions, prompting surgical resection. Histopathological examination revealed non-invasive HG PanIN/CIS in the MPD surrounded by dense fibrosis and fat deposition in the area of parenchymal atrophy. The CIS was restricted to the area of parenchymal atrophy.These two cases are noteworthy in illustrating a hypoechoic area appearing on EUS as a tumor-like lesion resembling PDAC. EUS-FNA has recently been used histopathologically to diagnose a pancreatic lesion. However, in the present and similar cases, EUS-FNA can only reveal secondary changes due to CIS unless the pancreatic duct covered by the CIS is accidentally punctured. We should bear in mind that CIS can appear as a hypoechoic area resembling PDAC on EUS, and that SPACE is the best method for diagnosing CIS in such cases.

An incorrect approach to the critical view of safety can cause bile duct and/or vascular injury. However, only superficial anatomical features have been proposed as surgical landmarks to initiate laparoscopic cholecystectomy (LC) safely in previous reports. Accordingly, we have proposed a novel surgical anatomical definition of the gallbladder wall, in which the subserosal (SS) layer is divided into the inner layer of the SS (SS-Inner) layer consisting of vasculature and fibrous tissue, and the outer layer of the SS (SS-Outer) layer consisting of abundant fat tissue. By dissecting the gallbladder along the SS-Inner layer after exposure at a safe region, bile duct and/or vascular injury can be avoided, even in cholecystitis cases. Furthermore, recognition of this surgical anatomy reveals several aspects. In cholecystitis cases associated with severe fibrotic change, completion of LC by dissecting along the SS-Inner layer is impossible, resulting in abandonment of regular LC. An abscess in the liver bed associated with acute cholecystitis usually forms in the SS-Outer layer, thus, the gallbladder can be dissected easily. In the dome-down technique, the right hepatic duct is endangered by whole-layer dissection, in which the SS-Outer layer is also removed. The proposed procedure should become the universal standard for LC.

Backgrounds: Endoscopic ultrasonography (EUS) is used to observe the stricture of the main pancreatic duct (MPD) and in diagnosing pancreatic cancer (PC). We investigate the findings on EUS by referring to the histopathological findings of resected specimens. Materials and Methods: Six patients with carcinoma in situ (CIS) and 30 patients with invasive carcinoma of 20 mm or less were included. The preoperative EUS findings were classified as follows. A1: Simple stricture type—no findings around the stricture; A2: Hypoecho stricture type—localized hypoechoic area without demarcation around the stricture; A3: Tumor stricture type—tumor on the stricture; B: Dilation type—the dilation of the pancreatic duct without a downstream stricture; C: Parenchymal tumor type—tumor located apart from the MPD. Results: Classes A1 and A2 consisted of 2 CISs, and 4 invasive carcinomas included two cases smaller than 5 mm in diameter. Most of the cancers classified as A3 or C were of invasive carcinoma larger than 5 mm in diameter. All cancers classified as B involved CIS. Serial pancreatic-juice aspiration cytologic examination (SPACE) was selected for all types of cases, with a sensitivity of 92.0%, while EUS-guided fine needle aspiration cytology (EUS-FNA) was only useful for invasive carcinoma, and its sensitivity was 66.7%. Conclusions: Stricture without a tumor could be a finding for invasive PC and pancreatic duct dilation without a downstream stricture could be a finding indicative of CIS. Carcinoma smaller than 5 mm in diameter could not be recognized by EUS. SPACE had a high sensitivity for diagnosing small PC.

A randomized, controlled trial has begun to compare neoadjuvant chemotherapy using gemcitabine and S-1 with upfront surgery for patients planned resection of pancreatic cancer. Patients were enrolled after the diagnosis of resectable or borderline resectable by portal vein involvement pancreatic cancer with histological confirmation. They were randomly assigned to either neoadjuvant chemotherapy or upfront surgery. Adjuvant chemotherapy using S-1 was administered for 6 months to patients with curative resection who fully recovered within 10 weeks after surgery in both arms. The primary endpoint is overall survival; secondary endpoints include adverse events, resection rate, recurrence-free survival, residual tumor status, nodal metastases and tumor marker kinetics. The target sample size was required to be at least 163 (alpha-error 0.05; power 0.8) in both arms. A total of 360 patients were required after considering ineligible cases. This trial began in January 2013 and was registered with the UMIN Clinical Trials Registry (UMIN000009634).

We propose a new flowchart for the treatment of acute cholecystitis (AC) in the Tokyo Guidelines 2018 (TG18). Grade III AC was not indicated for straightforward laparoscopic cholecystectomy (Lap-C). Following analysis of subsequent clinical investigations and drawing on Big Data in particular, TG18 proposes that some Grade III AC can be treated by Lap-C when performed at advanced centers with specialized surgeons experienced in this procedure and for patients that satisfy certain strict criteria. For Grade I, TG18 recommends early Lap-C if the patients meet the criteria of Charlson comorbidity index (CCI) ≤5 and American Society of Anesthesiologists physical status classification (ASA-PS) ≤2. For Grade II AC, if patients meet the criteria of CCI ≤5 and ASA-PS ≤2, TG18 recommends early Lap-C performed by experienced surgeons; and if not, after medical treatment and/or gallbladder drainage, Lap-C would be indicated. TG18 proposes that Lap-C is indicated in Grade III patients with strict criteria. These are that the patients have favorable organ system failure, and negative predictive factors, who meet the criteria of CCI ≤3 and ASA-PS ≤2 and who are being treated at an advanced center (where experienced surgeons practice). If the patient is not considered suitable for early surgery, TG18 recommends early/urgent biliary drainage followed by delayed Lap-C once the patient's overall condition has improved. Free full articles and mobile app of TG18 are available at: http://www.jshbps.jp/modules/en/index.php?content_id=47. Related clinical questions and references are also included.

Although the diagnostic and severity grading criteria on the 2013 Tokyo Guidelines (TG13) are used worldwide as the primary standard for management of acute cholangitis (AC), they need to be validated through implementation and assessment in actual clinical practice. Here, we conduct a systematic review of the literature to validate the TG13 diagnostic and severity grading criteria for AC and propose TG18 criteria. While there is little evidence evaluating the TG13 criteria, they were validated through a large-scale case series study in Japan and Taiwan. Analyzing big data from this study confirmed that the diagnostic rate of AC based on the TG13 diagnostic criteria was higher than that based on the TG07 criteria, and that 30-day mortality in patients with a higher severity based on the TG13 severity grading criteria was significantly higher. Furthermore, a comparison of patients treated with early or urgent biliary drainage versus patients not treated this way showed no difference in 30-day mortality among patients with Grade I or Grade III AC, but significantly lower 30-day mortality in patients with Grade II AC who were treated with early or urgent biliary drainage. This suggests that the TG13 severity grading criteria can be used to identify Grade II patients whose prognoses may be improved through biliary drainage. The TG13 severity grading criteria may therefore be useful as an indicator for biliary drainage as well as a predictive factor when assessing the patient's prognosis. The TG13 diagnostic and severity grading criteria for AC can provide results quickly, are minimally invasive for the patients, and are inexpensive. We recommend that the TG13 criteria be adopted in the TG18 guidelines and used as standard practice in the clinical setting. Free full articles and mobile app of TG18 are available at: http://www.jshbps.jp/modules/en/index.php?content_id=47. Related clinical questions and references are also included.

Background The aim of the present study was to clarify the surgical outcome and long-term prognosis of laparoscopic liver resection (LLR) compared with conventional open liver resection (OLR) in patients with colorectal liver metastases (CRLM). Methods A one-to-two propensity score matching (PSM) analysis was applied. Covariates (P

The International Summit on Laparoscopic Pancreatic Resection (ISLPR) was held in Coimbatore, India, on 7th and 8th of October 2016 and thirty international experts who regularly perform laparoscopic pancreatic resections participated in ISPLR from four continents, i.e., South and North America, Europe and Asia. Prior to ISLPR, the first conversation among the experts was made online on August 26th, 2016 and the structures of ISPLR were developed. The aims of ISPLR were; i) to identify indications and optimal case selection criteria for minimally invasive pancreatic resection (MIPR) in the setting of both benign and malignant diseases; ii) standardization of techniques to increase the safety of MIPR; iii) identification of common problems faced during MIPR and developing associated management strategies; iv) development of clinical protocols to allow early identification of complications and develop the accompanying management plan to minimize morbidity and mortality. As a process for interactive discussion, the experts were requested to complete an online questionnaire consisting of 65 questions about the various technical aspects of laparoscopic pancreatic resections. Two further web-based meetings were conducted prior to ISPLR. Through further discussion during ISPLR, we have created productive statements regarding the topics of Disease, Implementation, Patients, Techniques, and Instrumentations (DIPTI) and hereby publish them as “Coimbatore Summit Statements”.

Background We previously identified 25 intraoperative findings during laparoscopic cholecystectomy (LC) as potential indicators of surgical difficulty per nominal group technique. This study aimed to build a consensus among expert LC surgeons on the impact of each item on surgical difficulty. Methods Surgeons from Japan, Korea, and Taiwan (n = 554) participated in a Delphi process and graded the 25 items on a seven-stage scale (range, 0–6). Consensus was defined as (1) the interquartile range (IQR) of overall responses ≤2 and (2) ≥66% of the responses concentrated within a median ± 1 after stratification by workplace and LC experience level. Results Response rates for the first and the second-round Delphi were 92.6% and 90.3%, respectively. Final consensus was reached for all the 25 items. ‘Diffuse scarring in the Calot's triangle area’ in the ‘Factors related to inflammation of the gallbladder’ category had the strongest impact on surgical difficulty (median, 5; IQR, 1). Surgeons agreed that the surgical difficulty increases as more fibrotic change and scarring develop. The median point for each item was set as the difficulty score. Conclusions A Delphi consensus was reached among expert LC surgeons on the impact of intraoperative findings on surgical difficulty.