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Background: Neoadjuvant treatment (NAT) is standard for borderline resectable pancreatic cancer (BRPC). However, consensus is lacking on the optimal surgical timing for patients with BRPC undergoing NAT. The aim of this study was to investigate the long-term outcomes of patients undergoing NAT for BRPC and suggest optimal resection timing., Methods: Prospectively collected data for 282 patients with BRPC between January 2007 and December 2019 were retrospectively reviewed. There were 164 patients who underwent NAT followed by surgery, 45 for chemotherapy only, and 73 for upfront surgery. Among them, 150 patients who underwent R0 or R1 resection following NAT were investigated to identify prognostic factors., Results: Patients receiving NAT followed by surgery showed the best survival (median overall survival [OS]; NAT followed by surgery vs. upfront surgery vs. chemotherapy only; 35 vs. 23 vs. 16 months). In the NAT group, 54 (36.0%) patients received less than 3 months of NAT, 68 (45.3%) received ≥3, <6 months, and 28 (18.7%) received longer than 6 months. Patients receiving ≥3 months of NAT showed an improved OS compared to <3 months (median; not reached vs. 27 months). In the FOLFIRINOX group, patients who received more than eight FOLFIRINOX cycles showed a good prognosis (<6 vs. 6-7 vs. ≥8 cycles; median survival, 26 vs. 41 months vs. not-reached). However, >12 cycles did not carry a survival benefit compared to 8-11 cycles., Conclusion: The optimal resection timing following NAT is once a patient undergoes at least 3 months of neoadjuvant chemotherapy or at least eight FOLFIRINOX cycles., (© 2024 Japanese Society of Hepato‐Biliary‐Pancreatic Surgery.)

Background: Advances in chemotherapy have led to increasing major vascular resection during pancreatectomy which has been contraindicated due to high morbidity. This study aimed to verify the safety and oncological outcomes of vascular resection during pancreatectomy in the era of neoadjuvant therapy., Methods: Data from patients who underwent surgery for pancreatic cancer at Seoul National University Hospital between 2001 and 2021 were reviewed. Clinicopathological outcomes were analyzed according vessel resection. A propensity-score-matched (PSM) analysis was performed to evaluate survival outcomes., Results: Of 1596 patients, the proportion of those who underwent vascular resection increased from 9.2% to 23.4% over time divided into 5-year intervals. There were no differences in major complications (15.6% vs. 13.0%; p = .266) and 30-day mortality rate (0.3% vs. 0.6%; p = .837) between the vascular and nonvascular resection groups. After PSM, the vascular resection group demonstrated comparable survival outcome with the nonvascular resection group (5 year-survival-rate 20.4 vs. 23.7%; p = .194). Arterial resection yielded comparable survival outcome with nonvascular resection (5 year-survival-rate 38.1% vs. 23.7%; p = .138)., Conclusions: Appropriate vascular resection-even arterial-is safe and effective in patients carefully selected for radical surgery in the era of neoadjuvant therapy. Further studies are needed to determine the optimal indication and method for vascular resection in patients with pancreatic cancer., (© 2024 Japanese Society of Hepato‐Biliary‐Pancreatic Surgery.)

Background: Approximately 50% of pancreatic cancer cases are diagnosed with distant metastases, commonly in the liver, leading to poor prognosis. With modern chemotherapy regimens extending patient survival and stabilizing metastasis, there has been a rise in the use of local treatments. However, the effectiveness for local treatment remains unclear., Methods: PubMed, Embase, and Cochrane databases were searched for studies reporting the survival outcomes of pancreatic cancer cases with isolated synchronous or metachronous liver metastases who underwent curative-intent local treatment. Hazard ratios were combined using a random-effects model., Results: The full texts of 102 studies were screened, and 14 retrospective studies were included in the meta-analysis. Among patients with synchronous liver metastases, overall survival was significantly better in those who underwent curative-intent local treatment than in those who did not (hazard ratio [HR]: 0.35, 95% confidence interval [CI]: 0.24-0.52). Among patients with metachronous liver metastases, overall survival was also significantly better in those who underwent curative-intent local treatment than in those who did not (HR 0.37, 95% CI: 0.19-0.73)., Conclusions: Curative-intent local treatment may be a feasible option for highly selected pancreatic cancer cases with liver metastases. However, the optimal strategy for local treatments should be explored in future studies., (© 2024 Japanese Society of Hepato‐Biliary‐Pancreatic Surgery.)

Background: Although surgical resection is the only curative treatment for biliary tract cancer, in some cases, the disease is diagnosed as unresectable at initial presentation. There are few reports of conversion surgery after the initial treatment for unresectable locally advanced biliary tract cancer. This study aimed to evaluate the efficacy and safety of conversion surgery in patients with initially unresectable locally advanced biliary tract cancer., Methods: We retrospectively collected clinical data from groups of patients in multiple centers belonging to the Japanese Society of Hepato-Biliary-Pancreatic Surgery and Korean Association of Hepato-Biliary-Pancreatic Surgery. We analyzed two groups of prognostic factors (pretreatment and surgical factors) and their relation to the treatment outcomes., Results: A total of 56 patients with initially unresectable locally advanced biliary tract cancer were enrolled in this study of which 55 (98.2%) patients received chemotherapy, and 16 (28.6%) patients received additional radiation therapy. The median time from the start of the initial treatment to resection was 6.4 months. Severe postoperative complications of Clavien-Dindo grade III or higher occurred in 34 patients (60.7%), and postoperative mortality occurred in five patients (8.9%). Postoperative histological results revealed CR in eight patients (14.3%). The median survival time from the start of the initial treatment in all 56 patients who underwent conversion surgery was 37.7 months, the 3-year survival rate was 53.9%, and the 5-year survival rate was 39.1%., Conclusions: Conversion surgery for initially unresectable locally advanced biliary tract cancer may lead to longer survival in selected patients. However, more precise preoperative safety evaluation and careful postoperative management are required., (© 2024 Japanese Society of Hepato‐Biliary‐Pancreatic Surgery.)

Background: This multicenter study aimed to compare the clinical outcomes of minimally invasive extended cholecystectomy (MI-EC) versus open EC (O-EC) for patients with gallbladder cancer (GBC)., Methods: Patients who underwent EC (cholecystectomy, wedge resection of the liver bed, and regional lymphadenectomy) for GBC between 2010 and 2020 in three centers were included in the study. The clinicopathological data were compared after propensity score matching. Additional subgroup analysis on laparoscopic and robotic EC (L-EC and R-EC) was performed., Results: A total of 377 patients were included: 308 for O-EC and 69 for MI-EC, respectively. The MI-EC group had a longer operative time (188.9 vs. 238.1 min, p < .001) and shorter hospital stay (9.0 vs. 7.2 days, p = .007), although no differences were found in operative blood loss, complication rate and survival outcome. In subgroup analysis, L-EC patients had a longer operative time (264.4 vs. 202.0 min, p = .001), compared to R-EC patients with comparable perioperative and survival outcomes., Conclusion: Although patients with MI-EC had a longer operation time and higher medical costs, the advantages were enhanced recovery with comparable short- and long-term outcomes. The operation time was less for R-EC patients than for L-EC patients, though the high cost still remains. The surgery type for EC can be selected according to the patient's condition, social status and surgeon's preference., (© 2024 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: Although attempts of local treatment for isolated liver recurrence in patients with pancreatic ductal adenocarcinoma (PDAC) have increased, the efficacy remains unclear. Therefore, we aimed to evaluate the effect of local treatment for recurrent liver lesions after pancreatectomy on the survival of patients with PDAC., Methods: Patients who were diagnosed with isolated liver recurrence after pancreatectomy at a high-volume center were included. We classified these patients based on the treatment options after recurrence and performed propensity score matching to minimize confounding., Results: Median with interquartile range survival after recurrence was significantly longer for patients who underwent local treatment for recurrent liver lesions plus chemotherapy (22.0 [17.0-29.0] months) than those treated with chemotherapy alone (13.0 [7.0-21.0] months, p = .027). In multivariate analysis, not only local treatment for recurrent liver lesions plus chemotherapy (hazard ratio [95% confidence interval], 0.55 [0.32-0.94]; p = .030) but also indicators for systemically controlled tumor such as late recurrence (0.57 [0.35-0.92]; p = .021), chemotherapy for ≥6 months (0.25 [0.15-0.42]; p < .001), and disease control by chemotherapy (0.36 [0.22-0.60]; p < .001) were identified as favorable prognostic factors., Conclusions: PDAC patients with stable recurrent liver lesions should be considered a candidate for local treatment., (© 2023 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background/purpose: Little is known about the features of T1 pancreatic ductal adenocarcinoma (PDAC) and its definition in the eighth edition of the American Joint Committee on Cancer (AJCC) staging system needs validation. The aims were to analyze the clinicopathologic features of T1 PDAC and investigate the validity of its definition., Method: Data from 1506 patients with confirmed T1 PDAC between 2000 and 2019 were collected and analyzed. The results were validated using 3092 T1 PDAC patients from the Surveillance, Epidemiology, and End Results (SEER) database., Results: The median survival duration of patients was 50 months, and the 5-year survival rate was 45.1%. R0 resection was unachievable in 10.0% of patients, the nodal metastasis rate was 40.0%, and recurrence occurred in 55.2%. The current T1 subcategorization was not feasible for PDAC, tumors with extrapancreatic extension (72.8%) had worse outcomes than those without extrapancreatic extension (median survival 107 vs. 39 months, p < .001). Extrapancreatic extension was an independent prognostic factor whereas the current T1 subcategorization was not. The results of this study were reproducible with data from the SEER database., Conclusion: Despite its small size, T1 PDAC displayed aggressive behavior warranting active local and systemic treatment. The subcategorization by the eighth edition of the AJCC staging system was not adequate for PDAC, and better subcategorization methods need to be explored. In addition, the role of extrapancreatic extension in the staging system should be reconsidered., (© 2023 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: In an era of more effective chemotherapy for pancreatic ductal adenocarcinoma (PDAC), the paradigm of local treatment is changing. However, the efficacy of local treatment in patients with isolated liver metastasis remains unclear. Therefore, we aimed to evaluate the effectiveness of pancreatectomy ± local treatment for metastasis (cytoreductive surgery) in PDAC patients with isolated synchronous liver metastasis., Methods: In total, 239 patients with isolated liver metastasis were extracted from Seoul National University Hospital (SNUH). For comparison, another 12 637 patients were extracted from the National Cancer Database (NCDB). Propensity score matching was performed to minimize confounding in both cohorts. Survival analyses stratified by the treatment delivered were performed using Kaplan-Meier estimates and log-rank tests., Results: In the SNUH cohort, the median (interquartile range) survival was 20.5 (13.0-42.0) months for patients who underwent cytoreductive surgery plus chemotherapy versus 12.0 (10.0-18.0) months for those who received chemotherapy alone (P < .001). With the NCDB cohort, the median (interquartile range) survival was 15.6 (8.9-31.2) months for patients who underwent cytoreductive surgery plus chemotherapy versus 7.4 (3.4-13.2) months for those who received chemotherapy alone (P < .001)., Conclusion: Patients with isolated synchronous liver metastasis should be considered for cytoreductive surgery in addition to effective chemotherapy., (© 2023 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: A score derived from the concentrations of α-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) and tumor volume (TV), called ADV score, has been shown to be prognostic of hepatocellular carcinoma (HCC) recurrence following hepatic resection (HR) or liver transplantation., Methods: This multicenter, multinational validation study included 9200 patients who underwent HR from 2010 to 2017 at 10 Korean and 73 Japanese centers, and were followed up until 2020., Results: AFP, DCP, and TV showed weak correlations (ρ ≤ .463, r ≤ .189, p < .001). Disease-free survival (DFS), overall survival (OS), and post-recurrence survival rates were dependent on 1.0 log and 2.0 log intervals of ADV scores (p < .001). Receiver operating characteristic (ROC) curve analysis showed that ADV score cutoffs of 5.0 log for DFS and OS yielded the areas under the curve ≥ .577, with both being significantly prognostic of tumor recurrence and patient mortality at 3 years. ADV score cutoffs of ADV 4.0 log and 8.0 log, derived through K-adaptive partitioning method, showed higher prognostic contrasts in DFS and OS. ROC curve analysis showed that an ADV score cutoff of 4.2 log was suggestive of microvascular invasion, with both microvascular invasion and an ADV score cutoff of 4.2 log showing similar DFS rates., Conclusions: This international validation study demonstrated that ADV score is an integrated surrogate biomarker for post-resection prognosis of HCC. Prognostic prediction using ADV score can provide reliable information that can assist in planning treatment of patients with different stages of HCC and guide individualized post-resection follow-up based on the relative risk of HCC recurrence., (© 2023 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background/purpose: The efficacy of neoadjuvant treatment (NAT) for resectable pancreatic cancer remains debatable, particularly in patients with portal vein (PV)/superior mesenteric vein (SMV) contact and elevated serum carbohydrate antigen (CA) 19-9. This study investigated the clinical significance of PV/SMV contact and CA19-9 levels, and the role of NAT in resectable pancreatic cancer., Methods: A total of 775 patients who underwent surgery for resectable pancreatic cancer between 2007 and 2018 were included. Propensity score-matched (PSM) analysis (1:3) was performed based on tumor size, lymph node enlargement, and PV/SMV contact. Subgroup analyses were performed according to PV/SMV contact and CA19-9 level., Results: Among the patients, 52 underwent NAT and 723 underwent upfront surgery. After PSM, NAT group showed better survival than upfront surgery group (median 30.0 vs 22.0 months, P = .047). In patients with PV/SMV contact, NAT tended to have better survival (30.0 vs 22.0 months, P = .069). CA19-9 >150 U/mL was a poor prognostic factor, with NAT showing a significant survival difference compared with upfront surgery (34.0 vs 18.0 months, P = .004)., Conclusions: Neoadjuvant treatment showed better survival than upfront surgery in resectable pancreatic cancer. In patients with PV/SMV contact or CA19-9 >150 U/mL, NAT showed a survival difference compared to upfront surgery; therefore, NAT could be considered in these patients., (© 2023 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: In this study, we aimed to develop and validate a nomogram to predict overall survival (OS) and recurrence-free survival (RFS) in patients who underwent curative resection of ampulla of Vater (AOV) cancer. This is the first study for nomograms in AOV cancer patients using retrospective data based on an international multicenter study., Methods: A total of 2007 patients with AOV adenocarcinoma who received operative therapy between 2002 January and 2015 December in Korea and Japan were retrospectively assessed to develop a prediction model. Nomograms for 5-year OS and 3-year RFS were constructed by dividing the patients who received and who did not receive adjuvant therapy after surgery, respectively. Significant risk factors were identified by univariate and multivariate Cox analyses. Performance assessment of the four prediction models was conducted by the Harrell's concordance index (C-index) and calibration curves using bootstrapping., Results: A total of 2007 and 1873 patients were collected for nomogram construction to predict 5-year OS and 3-year RFS. We developed four types of nomograms, including models for 5-year OS and 3-year RFS in patients who did not receive postoperative adjuvant therapy, and 5-year OS and 3-year RFS in patients who received postoperative adjuvant therapy. The C-indices of these nomograms were 0.795 (95% confidence interval [CI]: 0.766-0.823), 0.712 (95% CI: 0.674-0.750), 0.804 (95% CI: 0.7778-0.829), and 0.703 (95% CI: 0.669-0.737), respectively., Conclusions: This predictive model could help clinicians to choose optimal treatment and precisely predict prognosis in AOV cancer patients., (© 2022 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: Previous studies have reported contrasting results regarding the advantages of spleen preservation during laparoscopic distal pancreatectomy (LDP) for preventing infectious complications., Methods: A total of 3787 patients who underwent LDP for benign or low-grade malignant pancreatic disease in 92 centers across Korea and Japan were included in this retrospective study. Postoperative infectious complications and other complications were compared between LDP with splenectomy (LDPS) and LDP with spleen preservation (LSPDP) by propensity score matching (PSM) analysis., Results: After PSM, the LSPDP group had a lower rate of overall infectious complications (P = .079) and a significantly lower rate of intra-abdominal abscess (P = .014) compared with the LDPS group. Within the LSPDP group, the vessel preservation subgroup had a significantly higher rate of infectious complications (P = .002) compared with the vessel resection subgroup. Low-volume centers had a higher rate of intra-abdominal abscess than high-volume centers in the LSPDP group (P = .001) and the splenic vessel preservation subgroup (P = .003)., Conclusions: Spleen preservation in LDP for benign or borderline malignant pancreatic diseases was advantageous in lowering the risk of infectious complications, specifically intra-abdominal abscess. However, the risk of intra-abdominal abscess may differ according to the level of surgeon's experience., (© 2022 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: Locally advanced (unresectable) pancreatic cancer (LAPC) is surgically unresectable and often treated with chemotherapy. Most previous studies, that have evaluated conversion surgery after chemotherapy, included heterogeneous patients and chemotherapy regimens, making it challenging to determine the impact of FOLFIRINOX. The present study evaluated the survival benefit of conversion surgery in patients with LAPC who received FOLFIRINOX chemotherapy, and analyzed the prognostic factors., Methods: Patients with LAPC who received FOLFIRINOX as first-line therapy for at least four cycles were included. During chemotherapy, surgical eligibility was determined based on radiologic and metabolic response to the treatment. Clinicopathologic characteristics were compared between the curative-intent surgery and non-resection groups, and the prognostic factors were analyzed., Results: A total of 279 patients were included. The rates of partial response (PR) and stable disease (SD) were 34.1% and 51.4%, respectively, and 16.8% patients underwent curative-intent surgery. The median survival was significantly longer in the resection group than in the non-resection group (56 vs 21 months, P < .001). In a multivariate analysis, curative-intent surgery (HR 0.260; P < .001) was the most important factor., Conclusions: Conversion surgery after FOLFIRINOX chemotherapy effectively rescues patients with LAPC. Patients without progression after FOLFIRINOX could be considered as potential candidates for conversion surgery., (© 2021 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background/purpose: The current study aimed to develop a prediction model using a multi-marker panel as a diagnostic screening tool for pancreatic ductal adenocarcinoma., Methods: Multi-center cohort of 1991 blood samples were collected from January 2011 to September 2019, of which 609 were normal, 145 were other cancer (colorectal, thyroid, and breast cancer), 314 were pancreatic benign disease, and 923 were pancreatic ductal adenocarcinoma. The automated multi-biomarker Enzyme-Linked Immunosorbent Assay kit was developed using three potential biomarkers: LRG1, TTR, and CA 19-9. Using a logistic regression model on a training data set, the predicted values for pancreatic ductal adenocarcinoma were obtained, and the result was classification into one of the three risk groups: low, intermediate, and high. The five covariates used to create the model were sex, age, and three biomarkers., Results: Participants were categorized into four groups as normal (n = 609), other cancer (n = 145), pancreatic benign disease (n = 314), and pancreatic ductal adenocarcinoma (n = 923). The normal, other cancer, and pancreatic benign disease groups were clubbed into the non-pancreatic ductal adenocarcinoma group (n = 1068). The positive and negative predictive value, sensitivity, and specificity were 94.12, 90.40, 93.81, and 90.86, respectively., Conclusions: This study demonstrates a significant diagnostic performance of the multi-marker panel in distinguishing pancreatic ductal adenocarcinoma from normal and benign pancreatic disease states, as well as patients with other cancers., (© 2021 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: Although we previously proposed a nomogram to predict malignancy in intraductal papillary mucinous neoplasms (IPMN) and validated it in an external cohort, its application is challenging without data on tumor markers. Moreover, existing nomograms have not been compared. This study aimed to develop a nomogram based on radiologic findings and to compare its performance with previously proposed American and Korean/Japanese nomograms., Methods: We recruited 3708 patients who underwent surgical resection at 31 tertiary institutions in eight countries, and patients with main pancreatic duct >10 mm were excluded. To construct the nomogram, 2606 patients were randomly allocated 1:1 into training and internal validation sets, and area under the receiver operating characteristics curve (AUC) was calculated using 10-fold cross validation by exhaustive search. This nomogram was then validated and compared to the American and Korean/Japanese nomograms using 1102 patients., Results: Among the 2606 patients, 90 had main-duct type, 900 had branch-duct type, and 1616 had mixed-type IPMN. Pathologic results revealed 1628 low-grade dysplasia, 476 high-grade dysplasia, and 502 invasive carcinoma. Location, cyst size, duct dilatation, and mural nodule were selected to construct the nomogram. AUC of this nomogram was higher than the American nomogram (0.691 vs 0.664, P = .014) and comparable with the Korean/Japanese nomogram (0.659 vs 0.653, P = .255)., Conclusions: A novel nomogram based on radiologic findings of IPMN is competitive for predicting risk of malignancy. This nomogram would be clinically helpful in circumstances where tumor markers are not available. The nomogram is freely available at http://statgen.snu.ac.kr/software/nomogramIPMN., (© 2021 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: Pancreatic resection has higher postoperative mortality and morbidity rates than other abdominal operations. Some centers have reported remarkable postoperative outcomes of minimally invasive surgery. This study investigated the chronological trends of pancreatectomies by analyzing a large-scale database., Methods: The medical records of 5175 patients who underwent pancreatic resection between 1961 and 2019 at a single institution were reviewed. To investigate the chronological change in survival outcomes of periampullary cancer, the survival data of 3,108 patients were analyzed., Results: Patient age and the proportion with pancreatic cancer have increased over time. From 2015 to 2019, pancreatic cancer was the most common cause for resection (35.9%), followed by pancreatic cysts (24.8%) and common bile duct cancer (13.4%). The incidence of postoperative complications tended to decrease over time (26.0% from 2000 to 2004; 20.8% from 2015 to 2019). A comparison of survival outcomes of periampullary malignancies by period revealed that patients with pancreatic cancer significantly improved (5-year survival rate: 14.4% before 2000% vs 15.2% from 2000 to 2009% vs 29.0% after 2009, P < .001)., Conclusions: Postoperative outcomes of pancreatic resection have improved over the past few decades. To improve outcomes in the future, an active multidisciplinary approach and postoperative management are required., (© 2021 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: To analyze serial changes in nutritional status, pancreatic function, and quality of life (QoL) over 5 years of follow-up after pancreatectomy., Methods: Patients undergoing pancreaticoduodenectomy (PD) or distal pancreatectomy (DP) between 2007 and 2013 were included. Data on relative body weight (RBW); triceps skinfold thickness (TSFT); body mass index (BMI); serum protein, albumin, transferrin, fasting blood glucose, postprandial 2-h glucose, and stool elastase levels; and QoL questionnaire scores were collected serially for 5 years., Results: Two hundred and seventeen patients were enrolled, but 79 patients completed the 5-year follow-up. RBW, BMI, and TSFT continued to decrease postoperatively but increased after 6 months. Transferrin, albumin, and protein levels recovered to the preoperative level after 3 months. Multivariate analysis revealed that a BMI >25 kg/m 2 , DP, and adjuvant therapy had a significant impact on endocrine pancreatic insufficiency. Although steatorrhea and diarrhea were mainly resolved by 12 months, the stool elastase level decreased after PD and was not restored. The mean scores for all QoL questionnaires improved above the preoperative value at 12 months., Conclusions: Patients undergoing pancreatectomy can return to their daily lives after 12 months. However, those with risk factors associated with pancreatic function and QoL need more careful follow-up and supportive management., (© 2020 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: Among various prognostic factors of pancreatic cancer, preoperative clinical information is obtained by imaging modality. This study aimed to evaluate clinical usefulness of preoperative carbohydrate antigen and preoperative standard uptake value in 18F-fluorodeoxyglucose positron emission tomography as predictive biological markers for resectable pancreatic ductal adenocarcinoma., Methods: A total of 189 patients with PDAC who underwent preoperative PET-computed tomography were evaluated. Patients underwent neoadjuvant chemotherapy, and R2 resection was excluded. The correlation between SUVmax and clinicopathologic parameters was analyzed. The C-tree statistical method was used to estimate cutoff values of logCA19-9 and SUVmax for survival rate. A multivariate analysis was conducted to identify prognostic factors for overall survival., Results: The median duration of OS was 26 months, and the 5-year survival rate was 22.4%. The optimal cutoff values for CA19-9 level was 150 U/mL and SUVmax was 5.5. When subjects were divided into three groups according to the combination of CA19-9 level and SUVmax from C-tree (high-risk group, CA19-9 > 150 U/mL and SUVmax > 5.5; intermediate-risk group, CA19-9 ≤ 150 U/mL and SUVmax > 5.5 or CA19-9 > 150 U/mL and SUVmax ≤ 5.5; and low-risk group, CA19-9 ≤ 150 U/mL and SUVmax ≤ 5.5), there was a significant 5YSR difference (5.6%, 24.3%, and 36.5%, P < .001). The multivariate analysis revealed high SUVmax, high preoperative CA19-9 level, venous invasion, and adjuvant chemotherapy were prognostic factors of OS., Conclusions: CA19-9 and SUVmax are strong prognostic biological factors in resectable PDAC. Moreover, patients with high CA19-9 level and SUVmax are not indicated for upfront surgery., (© 2020 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background/purpose: Surgical indications of main duct-involved intraductal papillary mucinous neoplasm (IPMN), especially for main pancreatic duct (MPD) of 5-9 mm, remain controversial. We aimed to predict malignancy risk of main duct-involved IPMN., Methods: Total 258 patients with main duct-involved IPMN between 2000 and 2017 in our institute were retrospectively analyzed. Main duct IPMN was classified into segmental and diffuse-type by dilated MPD pattern. Clinicopathologic features and predictive factors for malignancy were analyzed., Results: Among 258 patients, 47 and 211 had pure main duct (segmental: 27, diffuse type: 20) and mixed type, respectively. Malignant IPMN presented higher in main duct type (66.0%) compared to mixed type (46.9%). The diffuse type (72.2%) had more invasive carcinoma than the segmental type (40.7%). Invasive IPMN risk increased proportionally to the MPD diameter (5 ≤ MPD <10 mm vs 10 ≤ MPD < 15 mm vs MPD ≥ 15 mm; 23.4% vs 40.0% vs 48.6%). Symptoms, elevated serum carbohydrate antigen, MPD ≥10 mm, mural nodule, thickened wall, and distal atrophy were independent predictive factors for malignancy. Patients with MPD of 5-9 mm with at least one predictive factor had 35.0% of malignancy risk., Conclusions: The invasive IPMN risk was different according to the dilated main duct pattern. Patients with main duct type, diffuse type, MPD ≥10 mm, and MPD 5-9 mm with at least one predictive factor should be candidates for immediate surgery., (© 2022 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: A history of familial pancreatic cancer (FPC) increases the incidence of pancreatic cancer (PC) among first-degree relatives. We aimed to determine the incidence of FPC and analyze its clinical characteristics., Methods: Between 2010 and 2014, 1159 patients with PC were included in the study. We evaluated the incidence of FPC, clinicopathological features, and survival prognosis between FPC and non-FPC patients. We further analyzed the clinical outcomes of 389 patients with PC who underwent curative-intent surgery., Results: Familial pancreatic cancer incidence was 3.1% (n = 36) among all patients with PC (n = 1159). FPC was diagnosed at an advanced clinical stage compared to non-FPC (P = .041). The tested variables and 5-year survival rate (5YSR) between FPC and non-FPC after propensity score matching had no differences (5YSR: 4.6% vs 2.6%, P = .834). Among PC patients who underwent curative-intent surgery (n = 389), FPC incidence was 1.8% (n = 7). FPC patients were older than non-FPC patients (75.3 ± 4.7 years vs 64.0 ± 9.9 years, P < .001). 5YSR tended to differ between FPC and non-FPC (14.3% vs 22.5%, P = .07) groups., Conclusion: Familial pancreatic cancer is diagnosed at an advanced stage, and FPC that has undergone resection is associated with older age or worse prognosis. A prospective nationwide pedigree registration system was required., (© 2022 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background/purpose: We previously reported perioperative and oncologic outcomes of robot-assisted pancreatoduodenectomy (RAPD); however, the follow-up period in RAPD was relatively short, and disease-matched survival analyses were lacking. Therefore, this study investigated time trends of perioperative and long-term disease-matched outcomes of RAPD., Methods: Annual clinicopathologic outcomes of 328 patients with RAPD between 2015 and 2020 were analyzed and compared with 929 patients with open PD using the propensity score-matched (PSM) analysis based on postoperative pancreatic fistula (POPF) risk and oncologic variables in malignant patients., Results: Robot-assisted pancreatoduodenectomy cases increased from 10 (6.3%) in 2015 to 116 (50.2% of total PD) in 2020, with malignancy proportion increasing from 50.0% to 80.2%. POPF risk-based PSM analysis showed that compared with open PD, RAPD had younger patients (63.7 vs 65.6 years, P = .018), longer operation time (339.1 vs 290.0 min, P < .001); however, estimated blood loss (P = .275), complications (17.1% vs 18.3%, P = .702), and clinically relevant POPF (9.8% vs 11.1%, P = .584) were similar with shorter postoperative hospital stay (10.8 vs 15.6 days, P < .001). In disease and stage-matched malignant patients, R0 resection (93.9% vs 91.2%, P = .376), total retrieved lymph node (18.2 vs 19.9, P = .058), and 5-year survival rate (57.3% vs 60.6%, P = .406) were similar between RAPD and open PD, also in pancreatic cancer patients (31.6% vs 26.3%, P = .068)., Conclusions: Robot-assisted pancreatoduodenectomy demonstrated similar perioperative outcomes with earlier recovery and equivalent long-term survival with open PD. RAPD is safe and feasible for periampullary lesions, including pancreatic cancers, and its role will expand in the era of minimally invasive surgery., (© 2021 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: Factors aggravating remnant pancreas atrophy following pancreatoduodenectomy and the effects of atrophy have not been extensively studied. This study aimed to evaluate the clinical factors affecting remnant pancreas atrophy and assess the effects of atrophy on quality of life, nutritional status, and pancreatic exocrine and endocrine functions., Methods: Data collected prospectively from 122 patients who completed 12 months of follow-up, including computed tomography and the quality-of-life questionnaire, were analyzed. Pancreas volume was measured using a computed tomography volumetry program. Endocrine and exocrine functions were evaluated., Results: Malignancy and adjuvant chemoradiotherapy were associated with severity of atrophy. At 12 postoperative months, quality-of-life scores and nutritional indexes were mostly not associated with atrophy, but stool elastase level decreased significantly and incidence of new-onset diabetes mellitus was higher in the severe atrophy group. Postprandial 2-hour blood glucose and glycosylated hemoglobin levels were also higher in this group., Conclusions: Remnant pancreas atrophy was more severe in patients with malignant disease who received adjuvant chemoradiotherapy and was associated with pancreatic exocrine and endocrine functions. More careful monitoring and active management of exocrine and endocrine deficiencies are necessary for patients who underwent pancreatoduodenectomy for malignant disease and received chemoradiotherapy., (© 2021 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: Surgical views with high resolution and magnification have enabled us to recognize the precise anatomical structures that can be used as landmarks during minimally invasive distal pancreatectomy (MIDP). This study aimed to validate the usefulness of anatomy-based approaches for MIDP before and during the Expert Consensus Meeting: Precision Anatomy for Minimally Invasive HBP Surgery (February 24, 2021)., Methods: Twenty-five international MIDP experts developed clinical questions regarding surgical anatomy and approaches for MIDP. Studies identified via a comprehensive literature search were classified using Scottish Intercollegiate Guidelines Network methodology. Online Delphi voting was conducted after experts had drafted the recommendations, with the goal of obtaining >75% consensus. Experts discussed the revised recommendations in front of the validation committee and an international audience of 384 attendees. Finalized recommendations were made after a second round of online Delphi voting., Results: Four clinical questions were addressed, resulting in 10 recommendations. All recommendations reached at least a 75% consensus among experts., Conclusions: The expert consensus on precision anatomy for MIDP has been presented as a set of recommendations based on available evidence and expert opinions. These recommendations should guide experts and trainees in performing safe MIDP and foster its appropriate dissemination worldwide., (© 2021 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: The anatomical structure around the pancreatic head is very complex and it is important to understand its precise anatomy and corresponding anatomical approach to safely perform minimally invasive pancreatoduodenectomy (MIPD). This consensus statement aimed to develop recommendations for elucidating the anatomy and surgical approaches to MIPD., Methods: Studies identified via a comprehensive literature search were classified using the Scottish Intercollegiate Guidelines Network method. Delphi voting was conducted after experts had drafted recommendations, with a goal of obtaining >75% consensus. Experts discussed the revised recommendations with the validation committee and an international audience of 384 attendees. Finalized recommendations were made after a second round of online Delphi voting., Results: Three clinical questions were addressed, providing six recommendations. All recommendations reached at least a consensus of 75%. Preoperatively evaluating the presence of anatomical variations and superior mesenteric artery (SMA) and superior mesenteric vein (SMV) branching patterns was recommended. Moreover, it was recommended to fully understand the anatomical approach to SMA and intraoperatively confirm the SMA course based on each anatomical landmark before initiating dissection., Conclusions: MIPD experts suggest that surgical trainees perform resection based on precise anatomical landmarks for safe and reliable MIPD., (© 2021 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: Minimally invasive distal pancreatectomy (MIDP) was initially performed for benign tumors, but recently its indications have steadily broadened to encompass other conditions including pancreatic malignancies. Thorough anatomical knowledge is mandatory for precise surgery in the era of minimally invasive surgery. However, expert consensus regarding anatomical landmarks to facilitate the safe performance of MIDP is still lacking., Methods: A systematic literature search was performed using keywords to identify articles regarding the vascular anatomy and surgical approaches/techniques for MIDP., Results: All of the systematic reviews revealed that MIDP was not associated with an increase in postoperative complications. Moreover, most showed that MIDP resulted in less blood loss than open surgery. Regarding surgical approaches for MIDP, a standardized stepwise procedure improved surgical outcomes, including blood loss, operative time, and major complications. There are two approaches to the splenic vessels, superior and inferior; however, no study has ever directly compared them with respect to clinical outcomes. The morphology of the splenic artery affects the difficulty of approaching the artery's root. To select an appropriate dissecting layer when performing posterior resection, thorough knowledge of the anatomy of the fascia, left renal vein/artery, and left adrenal gland is needed., Conclusions: In MIDP, a standardized approach and precise knowledge of anatomy facilitates safe surgery and has the advantage of a shorter learning curve. Anatomical features and landmarks are particularly important in cases of radical MIDP and splenic vessel preserving MIDP., (© 2021 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: Although perioperative hypothermia was found to be associated with gastrointestinal anastomotic leakage in preclinical studies, its association with postoperative pancreatic fistula (POPF) following pancreaticoduodenectomy was never evaluated. We investigated the association between intraoperative hypothermia and clinically relevant (CR)-POPF following pancreaticoduodenectomy., Methods: We retrospectively reviewed 2163 consecutive patients who underwent pancreaticoduodenectomy during 2007-2019. Based on intraoperative time-weighted average core temperature, patients were grouped into normothermia (36.0-37.5°C), mild hypothermia (35.0-<36.0°C), and severe hypothermia (<35°C). We conducted multivariable logistic regression analysis for CR-POPF, a propensity score analysis using inverse probability of treatment weighting (IPTW) to adjust the baseline differences between the three groups, followed by multivariable logistic regression with IPTW for CR-POPF., Results: Among the 2008 patients analysed, 1118 (55.7%) and 120 (6.0%) had mild and severe hypothermia, respectively, and 14.2% overall incidence of CR-POPF. Severe intraoperative hypothermia was significantly associated with CR-POPF before and after IPTW (before: odds ratio [OR] 1.79, 95% confidence interval [CI]: 1.03-3.09, P = .038; after: OR 2.48, 95% CI: 1.28-4.81, P = .007); however, mild hypothermia had no significant associations., Conclusion: Severe intraoperative hypothermia is significantly associated with the occurrence of CR-POPF following pancreaticoduodenectomy, suggesting that hypothermia is deleterious on pancreaticojejunal anastomotic healing., (© 2021 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: Lymph node (LN) metastasis is a well-known poor prognostic factor of pancreatic cancer. LN metastasis, through direct invasion of tumor cell to peritumoral lymph nodes (PTLN), is treated as the same as those which spread through lymphatic channels. This study aimed to evaluate the impact of PTLN invasion on the oncologic outcome of pancreatic cancer., Methods: Five hundred and six patients who underwent operation for pancreatic ductal adenocarcinoma from 2012 to 2018 were reviewed. PTLN invasion was defined as direct invasion of tumor cells in contact with main tumor., Results: Among the 506 patients, 112 patients (22.1%) had PTLN invasion. PTLN invasion group (PTLNI) showed better disease-free survival than regional LN metastasis group (RLNM) and combined LN metastasis group (CLNM) (PTLNI 21 vs RLNM 11 vs CLNM 12 months, P = .003). There was no significant difference between N0 and PTLNI (PTLNI 21 vs N0 23 months, P = .999). In multivariate analysis, conventional LN metastasis was a significant factor compared to N0, but PTLN invasion was not (hazard ratio 0.786 [0.507-1.220], P = .283)., Conclusion: Because PTLN invasion does not adversely affect survival in the same way as LN metastasis does, pancreatic cancer-may be overstaged if PTLN invasion were dealt in the same manner as a metastatic LN. Therefore, PTLN invasion should be disregarded from current nodal staging system., (© 2021 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background/purpose: With the increase in detection of intraductal papillary mucinous neoplasms (IPMN), a tailored approach is needed. This study was aimed at exploring the natural history of IPMN and suggest optimal treatment based on malignancy risk using a nomogram and Markov decision model., Methods: Patients with IPMN who underwent surveillance or surgery were included. Changes in worrisome features/high-risk stigmata and malignancy conversion rate were assessed. Life expectancy and quality-adjusted life year (QALY) were compared using a nomogram predicting malignancy., Results: Overall, 2006 patients with histologically confirmed or radiologically typical IPMN were enrolled. Of these, 1773 (88.4%), 81 (4.0%), and 152 (7.6%), respectively, had branch duct (BD)-, main duct-, and mixed-type IPMN at initial diagnosis. The cumulative risk of developing worrisome feature or high-risk stigmata was 19.0% and 35.0% at 5- and 10-year follow-up, respectively. The progression of malignancy rate at 10-year follow-up was 79.9% for main and mixed IPMNs and 5.9% for BD-IPMN. Nomogram-based malignancy risk prediction is well correlated with natural history based on pathologic biopsy and shows good stratification of survival. The decision model recommends surgery to maximize survival and QALY especially in those with >35% malignancy risk., Conclusions: Compared with main duct- and mixed-type IPMN, which have a high risk of malignancy (79.9%), BD-IPMN is very indolent (5.9%). The nomogram-based decision model suggests surgery rather than surveillance for patients with a high malignancy risk. The optimal treatment strategy between surgery and surveillance should consider patients' health status, malignancy risk, and centers' experience., (© 2020 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background/purpose: The aim of the present study was to identify the types of recurrence in pancreatic ductal adenocarcinoma (PDAC) and discover the frequent location of the local recurrence., Methods: This study included 361 patients with PDAC who underwent curative-intent surgery between 2007-2014., Results: Among 361 patients, 75.1% (n = 271) developed recurrence during the follow-up period. The 5-year overall survival rate of recurred patients was 8.3%. The patterns of recurrence were classified as local (17.7%), systemic (62.0%), and loco-systemic (20.3%). According to the preoperative tumor locations, patients with uncinate and head cancer showed higher rates of local recurrence than those with body and tail cancer (47.8% vs 17.2%, P < .001). When comparing uncinate and head cancer only, patients with uncinate cancer had much more frequent local recurrence around the superior mesenteric artery/vein (M zone) than around the hepatoduodenal ligament/common hepatic artery (H zone). Patients with head cancer had a higher rate of local recurrence in the H zone (H zone vs M zone; 53.5% vs 81.4% in uncinate cancer, P = .001; 66.7% vs 44.4% in head cancer, P = .056)., Conclusion: Discovering the patterns of recurrence and frequent locations of recurrence may assist in local control as well as in the development of a customized individual approach for each patient., (© 2020 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background/purpose: Ampulla of Vater (AoV) carcinoma is a rare tumor that accounts for approximately 0.2% of gastrointestinal malignancies. There are no clinical guidelines concerning the treatment of AoV carcinoma. This study aimed to investigate the effectiveness of adjuvant treatment in AoV carcinoma following curative resection and define the "high-risk" group., Methods: Clinical data of patients who underwent curative resection for AoV carcinoma in four hospitals, namely Yonsei Gangnam Severance Hospital, Seoul National University Hospital, Seoul National University Bundang Hospital, and National Cancer Center (n = 651; 2002-2015), were reviewed. Overall survival (OS) and recurrence-free survival (RFS) rates were compared using Kaplan-Meier estimates., Results: Data of 651 patients who had undergone curative resection were retrospectively reviewed. Age, T stage, N stage, and differentiation type remained strong and independent risk factors for RFS and OS. In early-stage AoV carcinoma (T1N0, T2N0), the non-adjuvant group had better prognosis based on the RFS and OS than the adjuvant group (P < .001, P = .007). In advanced T stage (T3N0, T4N0), the adjuvant group had better prognosis than the non-adjuvant group, but the difference was not statistically significant (P > .05). In node-positive patients (any T, N1/2), adjuvant treatment did not affect RFS and OS (P > .05)., Conclusions: Adjuvant treatment after curative resection of AoV carcinoma is not associated with improved survival. The high-risk group (node-positive or advanced T stage (T3, T4)) treated with adjuvant treatment was not statistically associated with improved survival; however, our study showed that the adjuvant treatment for the high-risk group might help achieve better patient outcome., (© 2020 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: The prevalent location and incidence of intraductal papillary neoplasm of the bile duct (IPNB) and invasive carcinoma associated with them have varied markedly among studies due to differences in diagnostic criteria and tumor location., Methods: IPNBs were classified into two types: Type 1 IPNB, being histologically similar to intraductal papillary mucinous neoplasm of the pancreas, and Type 2 IPNB, having a more complex histological architecture with irregular papillary branching or foci of solid-tubular components. Medical data were evaluated., Results: Among 694 IPNB patients, 520 and 174 had Type 1 and Type 2, respectively. The levels of AST, ALT, ALP, T. Bil, and CEA were significantly higher in patients with Type 2 than in those with Type 1. Type 1 IPNB was more frequently located in the intrahepatic bile duct than Type 2, whereas Type 2 was more frequently located in the distal bile duct than Type 1 IPNB (P < 0.001). There were significant differences in 5-year cumulative survival rates (75.2% vs 50.9%; P < 0.0001) and 5-year cumulative disease-free survival rates (64.1% vs 35.3%; P < 0.0001) between the two groups., Conclusion: Type 1 and Type 2 IPNBs differ in their clinicopathological features and prognosis. This classification may help to further understand IPNB., (© 2020 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: It is currently unknown whether bile duct segmental resection (BDSR) is an acceptable method for localized middle bile duct cancer (mid-BDC) when R0 resection can be achieved. This study aimed to investigate the short- and long-term outcomes of mid-BDC patients treated with pancreaticoduodenectomy (PD) compared to those for BDSR., Methods: This was a retrospective, Japanese and Korean multi-center collaboration study based on patients' medical records., Results: A total of 663 patients, including 245 BDSR and 418 PD cases, were enrolled. The incidence of postoperative pancreatic fistula (3.3% vs 44.1%, P < .0001), surgical site infection in the organ space (6.1% vs 17.7%, P < .0001) and clinically problematic morbidities (15.9% vs 32.8%, P < .0001) was significantly higher in the PD group. There was no difference in the mortality rate (0.8% vs 1.7%, P = .3566). Local (33.9% vs 14.4%, P < .0001) and lymph node (22.4% vs 11.0%, P < .0001) recurrence rates were significantly higher in the BDSR group. Relapse-free survival (25.0 vs 34.0 months, P = .0184) and overall survival (41.2 vs 60.1 months, P = .0019) were significantly longer in the PD group. The PD group had significantly better prognosis in stage IA/IB cases (58.3 vs 111.5 months, P = .0067), which were the best indicators for BDSR, even when R0 resection was achieved. In multivariate analysis, BDSR was an independent poor prognostic factor., Conclusion: Despite the inferior perioperative short-term outcomes, our data advocate that PD should be the standard procedure for mid-BDCs and that BDSR should be avoided even if R0 resection can be achieved. (UMIN000017914)., (© 2020 The Authors. Journal of Hepato-Biliary-Pancreatic Sciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: Simple laparoscopic cholecystectomy is sufficient for patients with early gallbladder cancer (GBC). However, because advanced GBCs of T2 or more advanced stages require more complex procedures such as liver resection and lymph node dissection, minimally invasive surgery (MIS) has not been popularized. To evaluate the applicability of MIS for GBC, we report the early outcomes of robotic extended cholecystectomies (RECs)., Methods: Thirteen patients who radiologically suspected to have T2 or more advanced stages of GBC underwent REC from February 2018 to April 2019. Thirty-nine patients who underwent open extended cholecystectomy were selected by 1:3 propensity score matching, and the differences of clinicopathologic features according to surgical methods were analyzed., Results: Compared with open method, operation time, estimated blood loss, postoperative complication rate, and number of retrieved lymph nodes were not significantly different. In REC group, duration of hospital stay was shorter (6.6 vs 8.3 days, P = .002) and postoperative pain was significantly lower in the REC group (P = .024)., Conclusion: The early outcomes of REC were favorable with regard to early recovery and less pain, with similar number of retrieved lymph nodes. REC is a promising option for treatment of GBC, but further long-term survival studies are needed., (© 2020 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: The minimal required number of retrieved lymph nodes (MNRLNs) to enable accurate staging of distal bile duct (DBD) adenocarcinoma remains unclear. The three-tier 8th N staging system of the American Joint Committee on Cancer (AJCC) for DBD adenocarcinoma has been recently released. The present study is aimed at proposing the MNRLNs for accurate staging and validating the 8th N stage., Methods: Between 1991 and 2015, patients with pathologically confirmed DBD adenocarcinoma who underwent pancreatoduodenectomy were enrolled. MNRLN was calculated via a log-rank test based on cut-off values. The concordance index (C-index) was utilized to compare the discrimination capability of the two- and three-tier N stages., Results: A total of 780 patients were enrolled. Lymph node (LN) positivity and 5-year overall survival (5-YOS) rates stabilized and significant survival differences between node-negative and -positive patients were observed when ≥12 LNs were retrieved. 5-YOS rates between each 8th N stage significantly differ (N0 vs. N1, P = 0.037; N1 vs. N2, P = 0.003). The C-index of the 8th N stage was higher than that of the 7th (0.59 vs. 0.57)., Conclusions: For accurate staging, at least 12 LNs should be retrieved. The three-tier N staging system is valid for clinical practice and has a more accurate prognostic predictability than the two-tier system., (© 2019 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: With the increasing detection of pancreatic cysts, many centers have applied endoscopic ultrasound-guided pancreatic cyst ablation (EUS-PCA), even in intraductal papillary mucinous neoplasms (IPMNs) of the pancreas based on early promising outcomes. However, long-term effects of ethanol ablation have been rarely reported, especially regarding oncologic outcomes., Methods and Results: We report eight cases of malignancy conversion after EUS-PCA in patients with IPMNs who had worrisome features. Moreover, two patients showed tumor spillage or peritoneal seeding (carcinomatosis) after EUS-PCA., Conclusions: Endoscopic ultrasound-guided pancreatic cyst ablation must not be performed as a treatment for IPMNs, considering adverse results such as tumor spillage and the lack of oncological therapeutic effect., (© 2019 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: The introduction of FOLFIRINOX regimen greatly changed the treatment for advanced pancreatic cancers. However, detailed studies on the clinical effects and factors affecting the prognosis are insufficient. We performed this study to evaluate the effects of FOLFIRINOX and the surgical resection in advanced pancreatic cancer., Methods: Three hundred and thirty-seven patients with advanced pancreatic cancer who initially received FOLFIRINOX, from January 2011 to December 2017, were retrospectively reviewed. Patients were evaluated according to the National Comprehensive Cancer Network guideline, responses after four to six cycles of FOLFIRINOX were re-evaluated according to the response evaluation criteria in solid tumors, and further treatment was decided in the multidisciplinary meeting., Results: Sixty-seven (19.9%) patients had borderline resectable pancreatic cancer, 135 (40.1%) locally advanced pancreatic cancer, and 135 (40.1%) metastatic pancreatic cancer. The median survival period was significantly longer in the surgical group than in the nonsurgical group in each clinical stage, even in metastatic pancreatic cancer (32 vs. 14, P = 0.012). In multivariate analysis, metastatic status at diagnosis, progressive disease after FOLFIRINOX, surgical resection, and declined CA19-9 after FOLFIRINOX were significant prognostic factors., Conclusions: Surgical treatment greatly affects survival outcomes in advanced pancreatic cancer treated with FOLFIRINOX. Further studies on the optimal indication of operation and the protocol are needed., (© 2019 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: Few studies of the oncological outcomes of ampullary cancer have addressed recurrence, and many treatment-related issues remain unresolved. This study evaluated optimal surgical treatment strategies based on recurrence patterns after pancreaticoduodenectomy (PD) for ampullary cancer., Methods: Two hundred and fifty-nine patients who underwent PD with R0 resection for ampullary cancer from January 2000 to June 2012 were included. Generally, lymph node (LN) dissection extended to the right superior mesenteric artery (SMA). Recurrence was defined based on imaging studies. The first detected recurrence sites and patterns were analyzed., Results: During a mean follow-up of 51.3 months, recurrence occurred in 89 (34.4%) cases, most commonly in the liver. Poor differentiation, advanced T stage, and LN metastasis were identified as risk factors for recurrence. Locoregional and systemic recurrences occurred alone or simultaneously in 20.2%, 73.0%, and 6.7% of patients, respectively. Locoregional and systemic recurrences tended to occur in early- and advanced-stage cases, respectively. A nodal-type recurrence around mesenteric vessels was the most common locoregional recurrence pattern, and 58.8% (10/17) were located left of the SMA., Conclusion: As nodal-type metastasis around the mesenteric vessels was the dominant recurrence pattern, careful LN dissection around the SMA should be considered for early and advanced ampullary cancers., (© 2019 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: There is no consensus on the optimal treatment of T1b gallbladder cancer (GBC) due to the lack of evidence and the difficulty of anatomy and pathological standardization., Methods: A total of 272 patients with T1b GBC who underwent surgical resection at 14 centers with specialized hepatobiliary-pancreatic surgeons and pathologists in Korea, Japan, Chile, and the United States were studied. Clinical outcomes including disease-specific survival (DSS) rates according to the types of surgery were analyzed., Results: After excluding patients, the 237 qualifying patients consisted of 90 men and 147 women. Simple cholecystectomy (SC) was performed in 116 patients (48.9%) and extended cholecystectomy (EC) in 121 patients (51.1%). The overall 5-year DSS was 94.6%, and it was similar between SC and EC patients (93.7% vs. 95.5%, P = 0.496). The 5-year DSS was similar between SC and EC patients in America (82.3% vs. 100.0%, P = 0.249) as well as in Asia (98.6% vs. 95.2%, P = 0.690). The 5-year DSS also did not differ according to lymph node metastasis (P = 0.688) or tumor location (P = 0.474)., Conclusions: SC showed similar clinical outcomes (including recurrence) and survival outcomes as EC; therefore, EC is not needed for the treatment of T1b GBC., (© 2018 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: The aim of the present study was to compare the 7th and 8th editions of the American Joint Committee on Cancer (AJCC) staging system for pancreas head cancer and to validate the 8th edition using three multinational tertiary center data., Methods: Data of 2,864 patients with pancreas head cancer were collected from Korea (571), Japan (824), and the USA (1,469). Survival analysis was performed to compare the 7th and 8th editions. Validation was performed by log-rank tests and test for trend repeated 1,000 times with random sets., Results: In the 7th edition, 4.1%, 3.1%, 18.6%, 67.5%, 3.6%, and 3.1% were stage IA, IB, IIA, IIB, III, and IV. In the 8th edition, 8.8%, 13.9%, 3.1%, 38.2%, 32.9%, and 3.1% were stage IA, IB, IIA, IIB, III, and IV, respectively. The change in T category downstaged 459 patients from IIA to the new IA and IB. The new N2 category upstaged 856 patients from the former IIB to III. The 7th edition reversely stratified IA and IB. The 8th edition corrected this mis-stratification of the 7th edition, but lacked discriminatory power between IB and IIA (P = 0.271). Validation using the log-rank showed that the 8th edition provided better discrimination in 6.387 test sets among 10 tests. The test for trend validated the 8th edition to stratify stages in correct order more often (7.815/10)., Conclusion: The 8th edition provides more even distribution with more powerful discrimination compared to the 7th edition., (© 2018 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: The use of preoperative biliary drainage (PBD) for managing patients with periampullary cancer awaiting surgery remains controversial. The impact of PBD status and type on surgical outcomes has not been established, leading to a lack of consensus. We aimed to evaluate the impact of PBD on short-term surgical outcomes in curatively resected periampullary cancer., Methods: We retrospectively reviewed data from patients undergoing curative periampullary cancer resection. A propensity score-matched analysis was performed to adjust for clinical differences. Univariate and multivariate analyses were performed to determine independent risk factors for complications., Results: The overall complication rate was significantly higher in patients who underwent PBD (P = 0.027). Additionally, complication rates were significantly higher in the endoscopic biliary drainage (EBD) group than in the percutaneous transhepatic biliary drainage (PTBD) group (P < 0.001). After propensity score matching, overall complication rates in patients receiving EBD (P < 0.001) were significantly higher. PBD type and diagnosis were independent risk factors for complications (hazard ratios: 1.927 for EBD; 1.921 for biliary tract cancer)., Conclusions: Preoperative biliary drainage, especially EBD, should not be routinely performed in patients awaiting surgery for periampullary cancer, as it increases the risk of complications., (© 2017 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Intraductal papillary neoplasm of bile duct (IPNB) was described as a preinvasive neoplastic lesion of the biliary tract in the 2010 World Health Organization (WHO) classification. Although a number of studies have since been conducted on IPNBs, controversy remains, particularly regarding the standardization of its definition. Meetings by Japanese and Korean expert pathologists were held twice to resolve the pathological diagnostic aspects of IPNB. Through round-table discussions and histological reviews, we reached the common understanding that IPNBs diagnosed according to the criteria of WHO 2010 are characterized by intraductal predominant papillary or villous biliary neoplasms covering delicate fibrovascular stalks and are classified into two types pathologically. One type (type 1 IPNB) is histologically similar to intraductal papillary mucinous neoplasms of pancreas, and typically develops in the intrahepatic bile ducts, while the other (type 2 IPNB) has a more complex histological architecture with irregular papillary branching or with foci of solid-tubular components and typically involves the extrahepatic bile ducts. This report states the diagnostic pathologic features of IPNB proposed by WHO 2010. Since currently, the concept of IPNB is still confusing, the proposed diagnostic pathologic features stated here will be of use for future clinicopathological and molecular analyses toward consensus building of IPNB., (© 2017 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: The optimal surgical extent for T1 gallbladder cancer (GBC) remains controversial. Simple cholecystectomy is routinely performed for T1 GBC while several guidelines recommend extended cholecystectomy for T1b GBC. However, evidence regarding the optimal surgical extent for T1 GBC is lacking. This study aims to systematically evaluate the optimal surgical extent for early GBC with regard to long-term survival., Methods: A comprehensive literature search in MEDLINE was performed to identify studies with histologically proven GBC and survival data. A total of 22 articles with a total of 2,578 patients were included in the final analysis. Dichotomous data regarding cancer-related death in all T1, T1a, and T1b GBC cases were extracted. Risk ratios, risk differences, and 95% confidence intervals (CIs) were pooled., Results: The risk ratio between simple and extended cholecystectomy in T1 GBC patients was 1.06 (95% CI 0.97-1.16); T1a, 0.82 (95% CI 0.70-0.96); and T1b, 1.06 (95% CI 0.93-1.22). No significant difference was found according to the extent of surgery in all T1 or T1b GBC cases (P = 0.17 and P = 0.36, respectively). Simple cholecystectomy had significantly lower cancer-related death in T1a GBC patients (P = 0.01)., Conclusion: Simple and extended cholecystectomy showed comparable survival outcomes in T1 GBC patients., (© 2017 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: Robot surgery is a new method that maintains advantages and overcomes disadvantages of conventional methods, even in pancreatic surgery. This study aimed to evaluate safety and benefits of robot-assisted minimally invasive pancreaticoduodenectomy (robot PD)., Methods: This study included 237 patients who underwent PD between 2015 and 2017. Demographics and surgical outcomes were evaluated., Results: Fifty-one patients underwent robot PD and 186 underwent open PD. Robot PD group had younger age (60.7 vs. 65.4 years, P = 0.006) and lower body mass index (22.7 vs. 24.0, P = 0.007). Robot PD group had lower proportion of patients with firm or hard pancreatic texture (15.7% vs. 38.2%, P = 0.004) and smaller pancreatic duct size (2.3 vs. 3.3 mm, P = 0.002). Two groups had similar operation time (robot vs. open: 335.6 vs. 330.1 min) and complications (15.7% vs. 21.0%), including postoperative pancreatic fistula rate (6.0% vs. 12.0%). Robot PD group had lower postoperative pain score (3.7 vs. 4.1 points, P = 0.008), and shorter postoperative stay (10.6 vs. 15.3 days, P = 0.001)., Conclusion: Robot PD is comparable to open PD in early outcomes. Robot PD is safe and feasible and enables early recovery; indication for robot PD is expected to expand in the near future., (© 2017 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: The new 8th American Joint Committee on Cancer (AJCC) staging has recently been released and there are major changes in distal bile duct (DBD) cancer staging. However, clinical validation is needed before the changes can be widely implemented., Methods: This study was performed to evaluate the prognostic predictability of the 8th AJCC staging compared with that of the 7th using C statistics., Results: A total of 293 consecutive patients who had curative-intended surgery were enrolled. There was no significant difference of the 5-year survival rate between 7th T1 and T2 (P = 0.123), but significant difference between T2 and T3 (P = 0.039). There were significant differences in pairwise comparisons between the 8th T stage (T1 vs. T2, P = 0.001; T2 vs. T3, P = 0.014). The number of regional lymph node metastases also showed prognostic predictability. The 8th T and N stage both showed comparable prognostic predictability with the 7th (95% confidential intervals for C; T, -0.043 -0.097, N, -0.001 - 0.008)., Conclusions: The 8th AJCC staging for DBD cancer does not have better prognostic predictability than the 7th stage does. The previous pathologic results would become useless unless they were reviewed entirely. Therefore, introduction of the AJCC 8th staging has to be reconsidered, especially for new T staging., (© 2017 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: We built a multinational retrospective database of patients with ampulla of Vater cancer to develop a reliable new staging system., Method: This study included 841 patients with ampulla of Vater cancer after curative surgery at Seoul National University Hospital (n = 440) and Johns Hopkins University medical institutions (n = 401) between 1985 and 2013., Results: The 5-year overall survival (OS) rates of patients staged according to the 7 th American Joint Committee on Cancer staging system were 80.3%, 60.9%, 58.1%, 36.6%, 17.9%, and 25.0% for Stages IA (n = 140), IB (n = 194), IIA (n = 115), IIB (n = 348), III (n = 33), and IV (n = 4), respectively. Five-year OS rates were similar in patients with Stage IB (T2N0M0) and IIA (T3N0M0) tumors (P = 0.556), but differed significantly between other pairs of groups. The number of positive lymph nodes (PLN) enhanced prognosis when stratified as 0, 1-2 and ≥3 (P < 0.001). The revised staging system consisted of Stages I (T1, PLN 0), IIA (T2-T3, PLN 0), IIB (T1-T3, PLN 1-2), III (PLN ≥3 or any T4), and IV (any M1), with 5-year OS rates differing significantly in each pair of groups, including Stages I and IIA (P < 0.001)., Conclusion: This new staging system has better discriminatory ability in stratifying 5-year OS rates based on a large multinational database., (© 2017 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: Our previous randomized controlled trial revealed no difference in 2-year overall survival (OS) between extended and standard resection for pancreatic adenocarcinoma. The present study evaluated the 5-year OS and recurrence patterns according to the extent of pancreatectomy., Methods: Between 2006 and 2009, 169 consecutive patients were prospectively enrolled and randomized to standard (n = 83) or extended resection (n = 86) groups to compare 5-year OS rate, long-term recurrence patterns and factors associated with long-term survival., Results: The surgical R0 rate was similar between the standard and extended groups (85.5 vs. 90.7%, P = 0.300). Five-year OS (18.4 vs. 14.4%, P = 0.388), 5-year disease-free survival (14.8 vs. 14.0%, P = 0.531), and overall recurrence rates (74.7 vs. 69.9%, P = 0.497) were not significantly different between the two groups, although the incidence of peritoneal seeding was higher in the extended group (25 vs. 8.1%, P = 0.014)., Conclusions: Extended pancreatectomy does not have better short-term and long-term survival outcomes, and shows similar R0 rates and overall recurrence rates compared with standard pancreatectomy. Extended pancreatectomy does not have to be performed routinely for all cases of resectable pancreatic adenocarcinoma, especially considering its associated increased morbidity shown in our previous study., (© 2017 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

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., (© 2017 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: Several small-scale studies have shown that wrapping polyethylene glycolic acid (PGA) mesh around the anastomotic site reinforced pancreaticojejunostomy following pancreatoduodenectomy (PD) with favorable outcomes. This study investigated the efficacy of PGA mesh for reducing postoperative pancreatic fistula (POPF) and evaluated other risk factors for POPF., Methods: This study enrolled 464 consecutive patients who underwent PD performed by one surgeon between 2006 and 2015, including a PGA group of 281 patients (60.6%) and a control group of 183 patients (39.4%). All pancreatico-enteric anastomoses were performed using double-layered, duct-to-mucosa, end-to-side pancreaticojejunostomy., Results: Mean patient age was 63.1 years. The rates of overall (27.0% vs. 37.2%, P = 0.024) and clinically relevant (Grades B, C; 13.9% vs. 24.0%, P = 0.006) POPF were significantly lower in the PGA than in the control group. Following propensity score matching, the rates of clinically relevant POPF (12.6% vs. 22.4%, P = 0.024) and complications (40.2% vs. 63.8%, P < 0.001) remained significantly lower in the PGA group. Multivariate analysis showed that non-pancreatic disease, greater blood loss, higher body mass index, and non-application of PGA mesh were significantly associated with the development of clinically relevant POPF., Conclusions: PGA mesh reinforcement of pancreaticojejunostomy may prevent POPF as well as reducing overall abdominal complications after PD., (© 2017 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

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 ≥1,000)., 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 Rouvière'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., (© 2016 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)