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Supplementary Data from Comprehensive Genomic Profiling of Neuroendocrine Carcinomas of the Gastrointestinal System

Purpose: The prognosis of patients with advanced biliary tract cancer (BTC) is extremely poor and there are only a few standard treatments. We conducted a phase I trial to investigate the safety, immune response, and antitumor effect of vaccination with four peptides derived from cancer-testis antigens, with a focus on their fluctuations during long-term vaccination until the disease had progressed.Experimental Design: Nine patients with advanced BTC who had unresectable tumors and were refractory to standard chemotherapy were enrolled. HLA-A*2402–restricted epitope peptides, lymphocyte antigen 6 complex locus K, TTK protein kinase, insulin-like growth factor-II mRNA-binding protein 3, and DEP domain containing 1 were vaccinated subcutaneously once a week at doses of 0.5, 1, or 2 mg and continued until disease progression. The adverse events were assessed by Common Terminology Criteria for Adverse Events and the immune response was monitored by an enzyme-linked immunospot assay or by flow cytometry. The clinical effects observed were tumor response, progression-free survival (PFS), and overall survival (OS).Results: Four-peptide vaccination was well tolerated. No grade 3 or 4 adverse events were observed. Peptide-specific T-cell immune responses were observed in seven of nine patients and clinical responses were observed in six of nine patients. The median PFS and OS were 156 and 380 days. The injection site reaction and CTL induction seemed to be prognostic factors of both PFS and OS.Conclusions: Four-peptide vaccination was well tolerated and seemed to provide some clinical benefit to some patients. These immunologic and clinical responses were maintained over the long term through continuous vaccinations. Clin Cancer Res; 19(8); 2224–31. ©2013 AACR.

PDF File - 111K, Immunologic monitoring of each peptide-specific T cell response in each patient.

PDF File - 23K, Legends for Figures 1 and 2.

PDF File - 125K, An algorithm to define the responses of antigen-specific T cells by using the ELISPOT assay.

Whether organ-preserving pancreatic surgery has an advantage in postoperative short- and long-term outcomes or not is still unknown because only small case series studies have been available to date. In this multicenter retrospective study, we aimed to elucidate the clinical advantage and disadvantage of organ-preserving pancreatectomy among patients with low-grade malignant pancreatic tumors and benign pancreatic diseases.We included patients diagnosed with benign or low-malignant pancreatic tumor who underwent pancreaticoduodenectomy (PD) in 621 cases, duodenum-preserving pancreatic head resection (DPPHR) in 31 cases, middle pancreatectomy (MP) in 148 cases, distal pancreatectomy (DP) in 814 cases, and spleen-preserving distal pancreatectomy (SPDP) in 259 cases between January 1, 2013, and December 31, 2017. Preoperative backgrounds, surgical outcomes and pre- and postoperative (3, 6, 12, 24, and 36 months) nutritional status were compared between these procedures.In terms of short-term outcomes, the incidence of pancreatic fistula in patients who underwent MP was significantly higher than in patients with standard pancreatectomy. As for the long-term pancreatic functions in the cases of head or body lesion, both exocrine and endocrine functions after MP were significantly favorable compared with the PD group from 3 to 36 months after surgery. In pancreatic body or tail lesion, significant advantage of endocrine function, but not exocrine function, was found in the MP group compared to standard DP at all time points.MP may contribute to the improvement of postoperative quality of life for patients with pancreatic body low-malignant tumors, rather than PD or DP; however, reducing the incidence of short-term complications such as pancreatic fistula is a future challenge.

Although gemcitabine-based chemotherapy is the standard of care for advanced biliary tract cancers (BTCs), adjuvant phase III studies (BCAT in Japan, PRODIGE 12 in France) failed to show benefit, possibly owing to fewer patients (n = 225 and n = 194) compared with the adjuvant capecitabine BILCAP trial (n = 447). We performed a combined analysis of both gemcitabine-based chemotherapy adjuvant studies.We performed individual patient data meta-analysis of all patients included in BCAT and PRODIGE 12. BCAT study randomised patients with extrahepatic cholangiocarcinoma to single-agent gemcitabine or observation. PRODIGE 12 randomised patients with all BTC subtypes to gemcitabine-oxaliplatin combination or observation. Combined analysis was performed using Kaplan-Meier curves and a Cox regression model stratified on the trial.Two hundred and twelve versus 207 patients were randomised in the gemcitabine-based chemotherapy versus observation arms. Baseline characteristics were balanced between arms. The median follow-up was 5.5 years. After 258 relapse-free survival (RFS) events, there was no difference in RFS (log-rank p = 0.45; hazard ratio [HR] = 0.91 [95% confidence interval [CI] 0.71-1.16]; p = 0.46). RFS rates at five years were 40.8% (95%CI: 33.9%-47.5%) for gemcitabine-based chemotherapy versus 36.6% (95%CI: 29.8%-43.4%) for observation. After 201 deaths, there was no difference in overall survival (OS) (log-rank p = 0.83; HR = 1.03 [95%CI: 0.78-1.35]; p = 0.85). OS rates at five years were 50.5% (95%CI: 43.1%-57.4%) for gemcitabine-based chemotherapy versus 49.3% (95%CI: 41.6%-56.5%) for observation.With 419 patients included, this analysis did not show significant improvement in RFS and no trend in improvement in OS. Gemcitabine-based chemotherapy should not be used as an adjuvant treatment for BTC.

Preoperative treatment is being proposed as a standard treatment for pancreatic ductal adenocarcinoma though few cases show a pathologically complete response. On the other hand, there is no consensus regarding preoperative chemotherapy for pancreatic acinar cell carcinoma (ACC). The present study described a rare case of ACC in the pancreatic head with portal vein tumor thrombosis (PVTT) treated with preoperative chemotherapy using modified FOLFIRINOX, which achieved a pathologically complete response. A 65-year-old man was referred for consideration of treatment strategy. Contrast-enhanced abdominal computed tomography revealed a pancreatic tumor and PVTT. The pancreatic tumor was diagnosed as ACC by an endoscopic ultrasound-guided fine-needle aspiration biopsy. Initially, the tumor was assessed as unresectable due to the presence of PVTT, and therefore, a chemotherapy using modified FOLFIRINOX was administered. After 14 courses of the chemotherapy, imaging studies revealed that the tumor and PVTT showed marked reduction in size; thus, the patient underwent pancreaticoduodenectomy with combined resection of the portal vein (PV). A pathological examination uncovered a complete degeneration of the primary tumor and the PV embolus without any residue of carcinoma. The patient did not receive adjuvant chemotherapy and survived with no evidence of recurrence for 33 months after surgery. The chemotherapy using modified FOLFIRINOX could give a complete response in patients with pancreatic ACC with PVTT.

To clarify the short- and long-term postoperative outcomes and surgical indications for patients accompanied by hepatocellular carcinoma (HCC) with tumor thrombus (TT) in the inferior vena cava (IVC) or right atrium (RA).These patients are known to have an extremely poor prognosis; however, the postoperative outcomes have not been fully verified because of the rarity of this disease.We contacted 211 specialized centers in Japan and collected data on liver resection for HCC with TT in the IVC or RA from centers with experience performing surgery for such patients. The patient characteristics, operative procedures, and surgical outcomes were then analyzed.A total of 119 patients from 23 institutions were enrolled; 49 patients had TT in the IVC below the diaphragm (type I), 42 had TT in the IVC above the diaphragm (type II), and 28 had TT entering the RA (type III). The severity and frequency of postoperative complications did not differ among the three groups. There was one surgery-related death in the type III group. The median survival times were 2.47 years in the type I group, 1.77 years in the type II group, and 1.02 years in the type III group. A multivariate analysis identified an indocyanine green retention rate at 15 min15% and ≥3 tumors as prognostic factors affecting survival, while the use of cardiopulmonary bypass and ≥3 tumors were risk factors for recurrence.As the postoperative prognosis of patients with type I or type II disease and of patients with no risk factors is relatively good, surgery should be considered for these patient populations.

Although the number of minimally invasive liver resections (MILRs) has been steadily increasing in many institutions, minimally invasive anatomic liver resection (MIALR) remains a complicated procedure that has not been standardized. We present the results of a survey among expert liver surgeons as a benchmark for standardizing MIALR.We administered this survey to 34 expert liver surgeons who routinely perform MIALR. The survey contained questions on personal experience with liver resection, inflow/outflow control methods, and identification techniques of intersegmental/sectional planes (IPs).All 34 participants completed the survey; 24 experts (70%) had more than 11 years of experience with MILR, and over 80% of experts had performed over 100 open resections and MILRs each. Regarding the methods used for laparoscopic or robotic anatomic resection, the Glissonean approach (GA) was a more frequent procedure than the hilar approach (HA). Although hepatic veins were considered essential landmarks, the exposure methods varied. The top three techniques that the experts recommended for identifying IPs were creating a demarcation line, indocyanine green negative staining method, and intraoperative ultrasound.Minimally invasive anatomic liver resection remains a challenging procedure; however, a certain degree of consensus exists among expert liver surgeons.

Background: Gemcitabine together with nab-paclitaxel (GnP) has been shown to improve outcomes in patients with pancreatic ductal adenocarcinoma (PDAC). However, the predictive markers for treatment effects remain unclear. This study aimed to identify early prognostic factors in patients with PDAC receiving GnP. Patients and Methods: We analyzed 113 patients who received GnP for PDAC and evaluated the relationship between clinical factors and outcomes. Results: The median survival time (MST) was 1.2 years. In multivariate analysis, baseline carbohydrate antigen 19-9 (CA19-9) ≥747 U/ml [hazard ratio (HR)=1.9], baseline controlling nutrition status (CONUT) score ≥5 (HR=3.7) and changing rate of CA19-9 after two GnP cycles ≥0.69 (HR=3.7) were independent risk factors for poor prognosis. When examining outcomes according to pre-chemotherapeutic measurable factors (baseline CA19-9 and CONUT), the MSTs of patients with pre-chemotherapeutic zero risk factors (pre-low-risk group, n=63) and one or more risk factors (pre-high-risk group, n=50) were 1.7 and 0.65 years (p

OBJECTIVE: The aim of this study was to define robust benchmark values for the surgical treatment of perihilar cholangiocarcinomas (PHC) to enable unbiased comparisons. BACKGROUND: Despite ongoing efforts, postoperative mortality and morbidity remains high after complex liver surgery for PHC. Benchmark data of best achievable results in surgical PHC treatment are however still lacking. METHODS: This study analyzed consecutive patients undergoing major liver surgery for PHC in 24 high-volume centers in 3 continents over the recent 5-year period (2014-2018) with a minimum follow-up of 1 year in each patient. Benchmark patients were those operated at high-volume centers (≥50 cases during the study period) without the need for vascular reconstruction due to tumor invasion, or the presence of significant co-morbidities such as severe obesity (body mass index ≥35), diabetes, or cardiovascular diseases. Benchmark cutoff values were derived from the 75th or 25th percentile of the median values of all benchmark centers. RESULTS: Seven hundred eight (39%) of a total of 1829 consecutive patients qualified as benchmark cases. Benchmark cut-offs included: R0 resection ≥57%, postoperative liver failure (International Study Group of Liver Surgery): ≤35%; in-hospital and 3-month mortality rates ≤8% and ≤13%, respectively; 3-month grade 3 complications and the CCI: ≤70% and ≤30.5, respectively; bile leak-rate: ≤47% and 5-year overall survival of ≥39.7%. Centers operating mostly on complex cases disclosed better outcome including lower post-operative liver failure rates (4% vs 13%; P = 0.002). Centers from Asia disclosed better outcomes. CONCLUSION: Surgery for PHC remains associated with high morbidity and mortality with now the availability of benchmark values covering 21 outcome parameters, which may serve as key references for comparison in any future analyses of individuals, group of patients or centers.

Background: Analysis of operative data with convolutional neural networks (CNNs) is expected to improve the knowledge and professional skills of surgeons. Identification of objects in videos recorded during surgery can be used for surgical skill assessment and surgical navigation. The objectives of this study were to recognize objects and types of forceps in surgical videos acquired during colorectal surgeries and evaluate detection accuracy.Methods: Images (n=1818) were extracted from 11 surgical videos for model training, and another 500 images were extracted from 6 additional videos for validation. The following 5 types of forceps were selected for annotation: ultrasonic scalpel, grasping, clip, angled (Maryland and right-angled), and spatula. IBM Visual Insights software was used, which incorporates the most popular open-source deep-learning CNN frameworks.Results: In total, 1039/1062 (97.8%) forceps were correctly identified among 500 test images. Calculated recall and precision values were as follows: grasping forceps, 98.1% and 98.0%; ultrasonic scalpel, 99.4% and 93.9%; clip forceps, 96.2% and 92.7%; angled forceps, 94.9% and 100%; and spatula forceps, 98.1% and 94.5%, respectively.Conclusions: Forceps recognition can be achieved with high accuracy using deep-learning models, providing the opportunity to evaluate how forceps are used in various operations.

The current status and future prospects for diagnosis and treatment of lateral pelvic lymph node (LPLN) metastasis of rectal cancer are described in this review. Magnetic resonance imaging (MRI) is recommended for the diagnosis of LPLN metastasis. A LPLN-positive status on MRI is a strong risk factor for metastasis, and evaluation by MRI is important for deciding treatment strategy. LPLN dissection (LPLD) has an advantage of reducing recurrence in the lateral pelvis but also has a disadvantage of complications; therefore, LPLD may not be appropriate for cases that are less likely to have LPLN metastasis. Radiation therapy (RT) and chemoradiation therapy (CRT) have limited effects in cases with suspected LPLN metastasis, but a combination of preoperative CRT and LPLD may improve the treatment outcome. Thus, RT and CRT plus selective LPLD may be a rational strategy to omit unnecessary LPLD and produce a favorable treatment outcome.

Background Although thrombotic microangiopathy (TMA) is recognized as one of the poor-prognosis factors after liver transplantation, the precise outcome of TMA is unclear. We sought to elucidate the factors affecting the outcome of TMA after liver transplantation in Japan, based on the data from a nationwide survey. Methods One hundred cases of post-transplant TMA were accumulated from 17 Japanese centers of which 2 cases were excluded because the cause of death was obviously not related to TMA (recurrence of original diseases as primary sclerosing cholangitis and hepatocellular carcinoma), and remaining 98 cases were enrolled in this study. The patient survival after the development of TMA and the factors that affected the patients' outcomes were retrospectively analyzed. Results All cases were living-donor liver transplant cases, and the 1-, 3-, and 5-year patient survival rates after transplantation were 66.9%, 64.6%, and 62.2%, respectively. In a multivariate analysis, the requirement of renal replacement therapy during TMA treatment was the only factor that was significantly related to poor outcome after the development of TMA. Conclusion The outcomes of TMA were generally poor. The progression of renal dysfunction despite intensive treatment might be the only factor related to the poor prognosis after the development of TMA.

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.

Previous studies have reported contrasting results regarding the advantages of spleen preservation during laparoscopic distal pancreatectomy (LDP) for preventing infectious complications.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.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).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.

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 = 0.014) and comparable with the Korean/Japanese nomogram (0.659 vs 0.653, p = 0.255). 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.

Adult-onset Still’s disease (AOSD) is an inflammatory condition commonly complicated by mild liver dysfunction. However, severe liver failure is rarely reported. We report three cases of severe acute hepatic failure (ALF) associated with AOSD. We encountered three cases of acute liver failure (ALF) with encephalopathy. Case 1 was a 75-year-old female, who was started on a steroid (prednisolone, PSL) to treat AOSD; this was gradually tapered. Two months later, severe ALF developed. She died despite an increase in the PSL dose and artificial liver support. Case 2 was a 26-year-old-female taking PSL 30 mg/day to treat subacute thyroiditis. PSL was tapered, and she received methyl PSL pulse therapy and artificial liver support, but this did not cure the ALF. Liver transplantation (LT) was performed 25 days later. Three years later, the same symptoms were observed and we diagnosed AOSD. Case 3 was a 56-year-old-female who met the AOSD criteria. PSL 50 mg/day was started and then tapered. Methyl PSL pulse therapy was prescribed to treat hemophagocytic syndrome, but she required LT on hospital day 13. In AOSD cases, ALF is rarely complicated; urgent LT should be considered only for patients with AOSD-related severe ALF.

The controlling nutritional status (CONUT) score is a useful biomarker to evaluate undernutrition. However, there have been few reports describing the correlation between postoperative complications and the CONUT score for pancreatic cancer. Therefore, this study aimed to assess the impact of the CONUT score on the postoperative complications of pancreaticoduodenectomy (PD) in patients with pancreatic cancer. We retrospectively analyzed 206 consecutive patients with pancreatic cancer who underwent PD over a 12-year duration at our institution. The patients were divided into two groups based on preoperative CONUT scores; their clinicopathological characteristics and surgical outcomes were compared. Furthermore, we compared the CONUT score with preoperative clinical factors and several nutritional biomarkers for postoperative complications using univariate and multivariate analyses. Postoperative complications of Clavien–Dindo grade ≥ IIIa and those of Clavien–Dindo grade ≥ IIIb occurred in 29 (14.1%) and 9 (4.4%) patients, respectively. The high CONUT score (≥5) group indicated that patients with an undernutrition status had a higher postoperative complication rate, poorer relapse-free survival, and overall survival rates than the low CONUT score (≤4) group. Among preoperative clinical factors, a high CONUT score was an independent risk factor for severe postoperative complications. The CONUT score may be a useful parameter in the identification of patients undergoing pancreatic surgery who are susceptible to postoperative complications.

BACKGROUND The high operative mortality rate after hepatopancreatoduodenectomy (HPD) is still a major issue. The present study explored why operative mortality differs significantly due to hospital volume. METHOD Surgical case data were extracted from the National Clinical Database (NCD) in Japan from 2011 to 2014. Surgical procedures were categorized as major (≥2 sections) and minor (

BACKGROUND The Glissonean approach has been widely validated for both open and minimally invasive anatomic liver resection (MIALR). However, the possible advantages compared to the conventional hilar approach are still under debate. The aim of this systematic review was to evaluate the application of the Glissonean approach in MIALR. METHODS A systematic review of the literature was conducted on PubMed and Ichushi databases. Articles written in English or Japanese were included. From 2,390 English manuscripts evaluated by title and abstract, 43 were included. Additionally, 23 out of 463 Japanese manuscripts were selected. Duplicates were removed, including the most recent manuscript. RESULTS The Glissonean approach is reported for both major and minor MIALR. The 1st, 2nd and 3rd order divisions of both right and left portal pedicles can be reached following defined anatomical landmarks. Compared to the conventional hilar approach, the Glissonean approach is associated with shorter operative time, lower blood loss, and better peri-operative outcomes. CONCLUSIONS Glissonean approach is safe and feasible for MIALR with several reported advantages compared to the conventional hilar approach. Clear knowledge of Laennec's capsule anatomy is necessary and serves as a guide for the dissection. However, the best surgical approach to be performed depends on surgeon experience and patients' characteristics. Standardization of the Glissonean approach for MIALR is important.

To evaluate the surgical outcomes of patients with gallbladder cancer (GBC) with jaundice due to as-yet unelucidated prognostic factors. A total of 348 GBC patients underwent resection at our institute between 1985 and 2016. Of these, 67 had jaundice (serum total bilirubin ≥ 2 mg/dL). Preoperative biliary drainage was performed, with portal vein embolization as required. All patients underwent radical surgery. We retrospectively evaluated the outcomes, performed multivariate analysis for overall survival, and compared our findings to those reported in the literature. The 5-year survival rate of M0 (no distant metastasis) GBC patients with jaundice, who underwent resectional surgery, was 21.9%, versus 68.3% in those without jaundice (p < 0.05). Since 2000, surgical mortality in GBC patients with jaundice has decreased from 12 to 6.8%. Patients with jaundice had more advanced disease and underwent major hepatectomies and vascular resections; however, preoperative jaundice alone was not a prognostic factor. Multivariate analysis of jaundiced patients revealed that percutaneous biliary drainage (PTBD) (vis-a-vis endoscopic drainage [EBD], hazard ratio [HR] 2.82), postoperative morbidity (Clavien–Dindo classification ≥ 3, HR 2.31), and distant metastasis (HR 1.85) were predictors of poor long-term survival. The 5-year survival and peritoneal recurrence rates in M0 patients with jaundice were 16% and 44%, respectively, for patients with PTBD and 39% (p < 0.05) and 13% (p = 0.07) for those with EBD. M0 GBC patients with jaundice should undergo surgery if R0 resection is possible. Preoperative EBD may be superior to PTBD in M0 GBC patients with jaundice, although further studies are needed.

Purpose In this systematic review, we aimed to clarify the useful anatomic structures and assess available surgical techniques and strategies required to safely perform minimally invasive anatomic liver resection (MIALR), with a particular focus on the hepatic veins (HVs). Methods A systematic review was conducted using MEDLINE/PubMed for English articles and Ichushi databases for Japanese articles through September 2020. The quality assessment of the articles was performed in accordance with the Scottish Intercollegiate Guidelines Network (SIGN). Results A total of 3,372 studies were obtained, and 59 were selected and reviewed. Due to the limited number of published comparative studies and case series, the degree of evidence from our review was low. Thirty-two articles examined the anatomic landmarks and crucial structures for approaching HVs. Regarding the direction of HV exposure, 32 articles focused on the techniques and advantages of exposing HVs from either the root or the periphery. Ten articles focused on the techniques to perform a segmentectomy 8 in particularly difficult cases of MIALR. In seven articles, bleeding control from HVs was also discussed. Conclusions This review may help experts reach a consensus regarding the best approach to the management of hepatic veins during MIALR.

Background In preparation for the upcoming consensus meeting in Tokyo in 2021, this systematic review aimed to analyze the current available evidence regarding surgical anatomy of the liver, focusing on useful landmarks, strategies and technical tools to perform precise anatomic liver resection (ALR). Methods A systematic review was conducted on MEDLINE/PubMed for English articles and on Ichushi database for Japanese articles until September 2020. The quality assessment of the articles was performed in accordance with the Scottish Intercollegiate Guidelines Network (SIGN). Results A total of 3169 manuscripts were obtained, 1993 in English and 1176 in Japanese literature. Subsequently, 63 English and 20 Japanese articles were selected and reviewed. The quality assessment of comparative series and case series was revealed to be usually low; only six articles were qualified as high quality. Forty-two articles focused on analyzing intersegmental/sectional planes and their relationship with specific hepatic landmark veins. In 12 articles, the authors aimed to investigate liver surface anatomic structures, while 36 articles aimed to study technological tools and contrast agents for surgical segmentation during ALR. Although Couinaud's classification has remained the cornerstone in daily diagnostic/surgical practices, it does not always portray the realistic liver segmentation and there has been no standardization on which a single strategy should be followed to perform precise ALR. Conclusions A global consensus should be pursued in order to establish clear guidelines and proper recommendations to perform ALR in the era of minimally invasive surgery.

Objective Postoperative pancreatic fistula (POPF) is one of the severe complications that develop after pancreaticoduodenectomy (PD). This study aimed to assess the utility of preoperative clinicophysiologic findings as risk factors for POPF after PD. Summary of Background Data We enrolled 350 patients who underwent PD between 2007 and 2012 at Tokyo Women's Medical University. Methods In total, 350 patients who underwent PD between 2007 and 2012 were examined retrospectively. All patients were classified into 2 groups as follows: group A (no fistula/biochemical leak group, 289 patients) and group B (grade B/C of POPF group 61 patients). Variables, including operative characteristics, length of stay in hospital, morbidity, mortality, and data regarding preoperative clinicophysiologic parameters, were collected and analyzed as predictors of POPF for univariate and multivariate analyses. Results There were 213 male and 137 female patients. The mean age was 65.4 years (range, 21–87 years). Univariate analysis showed that sex (P = 0.047), amylase level (P = 0.032), prognostic nutritional index (PNI; P = 0.001), and C-reactive protein/albumin ratio (P = 0.005) were independent risk factors for POPF. In contrast, multivariate analysis showed that sex (P = 0.045) and PNI (P = 0.012) were independent risk factors for POPF. Conclusions Our results show that PNI (≤48.64 U/mL) and male sex were risk factors for POPF after PD, and especially, PNI can be suggested as an effective biomarker for POPF.

Aim We aimed to investigate whether later weekdays are related to worse short‐term outcomes after elective right hemicolectomy for colon cancer. Methods We retrospectively analyzed adult patients who underwent elective right hemicolectomy for colon cancer between 2012 and 2017. Records lacking details about surgical mortality were excluded, and multiple imputation was performed for other missing data (variables). The primary endpoint was surgical mortality, defined as the sum of 30‐day mortality and in‐hospital deaths within 90 days postoperatively. Using 22 clinical variables, hierarchal logistic regression modeling with clustering of patients from the same institutes was performed. Results Of the 112 658 patients undergoing elective right hemicolectomy for colon cancer, the 30‐day mortality and surgical mortality were 0.6% and 1.1%, respectively. Surgery on Friday was less frequent, accounting for 17.1% of all cases. The occurrence of severe postoperative complications, anastomotic leakage, or unadjusted odds ratio for surgical mortality did not show significant differences between weekdays. A hierarchal logistic regression model identified 19 independent factors for surgical mortality. Adjusted odds ratios for surgical mortality were 1.01 (95% confidence interval: 0.83‐1.22, P = .915), 0.86 (95% confidence interval: 0.71‐1.05, P = .144), 0.86 (95% confidence interval: 0.71‐1.05, P = .408), and 0.83 (95% confidence interval: 0.68‐1.03, P = .176) for Tuesday, Wednesday, Thursday, and Friday, respectively, showing no significant differences. Conclusion This study did not identify an evident difference in surgical mortality between weekdays; a safe elective right hemicolectomy for colon cancer is being offered throughout the week in Japan., Weekday effect on mortality.

To evaluate the incidence, risk factors, management options, and outcomes of portal vein thrombosis following major hepatectomy for perihilar cholangiocarcinoma.A total of 177 perihilar cholangiocarcinoma patients who (1) underwent major hepatectomy and (2) underwent investigating the portal vein morphology, which was measured by rotating the reconstructed three-dimensional images after facilitating bone removal using Aquarius iNtuition workstation between 2002 and 2018, were included. Risk factors were evaluated using the Kaplan-Meier method and Cox proportional hazard models.Six patients developed portal vein thrombosis (3.4%) within a median time of 6.5 (range 0-22) days. Portal vein and hepatic artery resection were performed in 30% and 6% patients, respectively. A significant difference in the probability of the occurrence of portal vein thrombosis (PV) within 30 days was found among patients with portal vein resection, a postoperative portal vein angle100°, remnant portal vein diameter5.77 mm, main portal vein diameter13.4 mm, and blood loss (log-rank test, p = 0.003, p = 0.06, p0.0001, p = 0.01, and p = 0.03, respectively). Decreasing the portal vein angle and narrowing of the remnant PV diameter remained significant predictors on multivariate analysis (p = 0.027 and 0.002, respectively). Reoperation with thrombectomy was performed in four patients, and the other two patients were successfully treated with anticoagulants. All six patients subsequently recovered and were discharged between 25 and 70 days postoperatively.Narrowing of the remnant portal vein diameter and a decreased portal vein angle after major hepatectomy for perihilar cholangiocarcinoma are significant independent risk factors for postoperative portal vein thrombosis.

Background Hepatectomy is standard treatment for colorectal liver metastases; however, it is unclear whether liver metastases from other primary cancers should be resected or not. The Japanese Society of Hepato-Biliary-Pancreatic Surgery therefore created clinical practice guidelines for the management of metastatic liver tumors. Methods Eight primary diseases were selected based on the number of hepatectomies performed for each malignancy per year. Clinical questions were structured in the population, intervention, comparison, and outcomes (PICO) format. Systematic reviews were performed, and the strength of recommendations and the level of quality of evidence for each clinical question were discussed and determined. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess evidence and make recommendations. Results The eight primary sites were grouped into five categories based on suggested indications for hepatectomy and consensus of the guidelines committee. Fourteen clinical questions were devised, covering five topics: (1) diagnosis, (2) operative treatment, (3) ablation therapy, (4) the eight primary diseases, and (5) systemic therapies. The grade of recommendation was strong for one clinical question and weak for the other 13 clinical questions. The quality of the evidence was moderate for two questions, low for 10, and very low for two. A flowchart was made to summarize the outcomes of the guidelines for the indications of hepatectomy and systemic therapy. Conclusions These guidelines were developed to provide useful information based on evidence in the published literature for the clinical management of liver metastases, and they could be helpful for conducting future clinical trials to provide higher-quality evidence.

Background Upfront surgery is the standard treatment for resectable invasive intraductal papillary mucinous carcinoma; however, recurrence is common. Therefore, we investigated the recurrence, surgical outcome, and preoperative prognostic factors for recurrence in patients with resectable invasive intraductal papillary mucinous carcinoma. Methods We analyzed 111 patients who underwent upfront surgery for resectable invasive intraductal papillary mucinous carcinoma between 2000 and 2017 and evaluated the relationship among clinicopathologic factors, recurrence, and outcomes. Results The 5-year recurrence-free survival and disease-specific survival rates were 61% and 74%, respectively. The median time to recurrence was 1.1 years. In multivariate analysis, carbohydrate antigen 19-9 ≥83 U/mL (hazard ratio: 2.8 and 3.1), tumor size ≥2.2 cm (hazard ratio: 3.5 and 4.7), and pathologic tubular adenocarcinoma grade 2 (hazard ratio: 3.1 and 5.2) were risk factors for a shorter recurrence-free survival and disease-specific survival, respectively. Lymph node metastasis (hazard ratio: 3.9) was also a risk factor for a shorter disease-specific survival. When examining outcomes according to preoperatively measurable factors (carbohydrate antigen 19-9 ≥83 U/mL and tumor size ≥2.2 cm), the 5-year recurrence rates in patients with none (n = 47), 1 (n = 46), and both (n = 18) risk factors were 17%, 48%, and 78%, respectively. Five-year disease-specific survival rates in patients with none, 1, and both preoperative risk factors were 95%, 69%, and 31%, respectively. Conclusion Carbohydrate antigen 19-9 ≥83 U/mL and tumor size ≥2.2 cm were independent preoperative risk factors for poor outcomes in patients with resectable invasive intraductal papillary mucinous carcinoma.

We study the drift-diffusion equation with fractional dissipation $$(-\varDelta )^{\theta /2}$$ arising from a model of semiconductors. First, we prove the existence and uniqueness of the small solution to the corresponding stationary problem in the whole space. Moreover, it is proved that the unique solution of non-stationary problem exists globally in time and decays exponentially, if initial data are suitably close to the stationary solution and the stationary solution is sufficiently small.

A 70-year-old female was found to have multiple hepatic cysts at her annual checkup. In the posterior segment of the right lobe of the liver, an 81 × 67 mm circular cystic lesion was detected by contrast-enhanced computed tomography (CT). Magnetic resonance imaging (MRI) of the cyst revealed a solid component. The cyst had a capsule-like structure and non-uniform fluid accumulation suggested bleeding. Since the lesion was enlarged and malignancy could not be ruled out, it was surgically resected. Histopathologically, reticular fibers of the liver were seen in necrotic tissue and the lesion was diagnosed as a bleeding hepatocellular carcinoma (HCC). The non-cancerous liver tissue showed non-cirrhotic steatohepatitis. This was an unusual presentation of HCC.

Background Pouch volvulus after proctocolectomy for ulcerative colitis is a very rare postoperative complication. The common site of pouch volvulus has been reported to be the ileal pouch–anal anastomosis and the middle part of the pouch, but no reports on pouch volvulus in the afferent limb of the pouch have been observed. Here, we report the case of a patient with afferent limb volvulus who underwent afferent limbpexy, but required reoperation 7 months later. Case presentation A 38-year-old man with refractory ulcerative colitis had undergone open proctocolectomy 10 years ago at another hospital. He had been aware of lower abdominal pain and bowel movement difficulty for 2 years. After repeated bowel obstruction, he was referred to our hospital for surgery. Based on the radiographic findings, we diagnosed a pouch volvulus and performed an operation. Laparoscopically, counterclockwise rotation of the afferent limb of the pouch was recognized. Moreover, the ileal mesentery was adhered and fixed to the presacral space 20 cm from the oral side of the pouch. The antimesenteric side of the afferent limb was fixed using interrupted stiches on the left peritoneal wall of the pelvis. He was discharged uneventfully 18 days after surgery, and defecation improved immediately. However, he was readmitted 7 months after surgery with the same abdominal pain and defecation difficulty. A similar finding was found and diagnosed as recurrent volvulus. Therefore, we performed a laparoscopic surgery. The same volvulus as in the previous surgery was confirmed. The site fixed during the previous surgery showed scars, but the afferent limb was free. The dilated ileum that contained the volvulus was excised only on the oral side of the pouch and an intraluminal anastomosis was performed on the anterior wall of the pouch. He had a good postoperative course and was discharged. Conclusion Proper diagnosis of volvulus based on the characteristic imaging findings is important. In principle, bilateral row fixation of the rotated ileum is the basic procedure for volvulus. However, fixation with this technique is sometimes difficult. Therefore, this procedure is one of the useful options for the fixation of difficult or recurrent cases.

Aim: To find out differences in biomarkers between Japanese and German patients responsible for response after neoadjuvant radio/chemotherapy and survival for esophageal squamous cell carcinoma. Materials & methods: A total of 60 patients from Japan and 127 patients from Germany with esophageal squamous cell carcinoma were analyzed according to three SNPs by real-time PCR. Results: The distribution of the genotypes of ERCC1 rs16115 and ABCB1 C3435T rs1045642 was significantly different between both patients’ groups. Japanese patients had significantly less good response to 5-fluorouracil/cisplatin chemotherapy. The influence of the three SNPs on response varied between patients from Japan and Germany. Conclusion: Different expressions of ERCC1 and ABCB1 SNPs of Japanese patients compared with the German patients partially explain the different response.

Objective The primary objective of this study was to identify novel genes that predispose people in the Japanese population to FPC. Summary of background data Familial history of pancreatic cancer is an important risk factor but, to date, few genes predisposing individuals to increased risk of developing FPC have been identified. Methods We performed whole-exome sequencing of germline DNA from 81 Japanese FPC patients. We also investigated somatic gene alterations in 21 matched tumor tissues through whole-exome sequencing and copy number analysis. Results Our germline variants identified previously known FPC susceptibility genes such as ATM and BRCA2, and several novel tumor suppressor genes with potentially deleterious variants for FPC. Interestingly, somatic whole-exome analysis demonstrated that most tumor samples with suspicious loss of heterozygosity of candidate genes were KRAS wild-types, implying that these cases may not have required KRAS activation as a driver event for carcinogenesis. Conclusions Our findings indicate that FPC patients harbor potentially deleterious causative germline variants in tumor suppressor genes, which are known to acquire somatic mutations in pancreatic cancer, and that somatic loss of heterozygosity of some FPC susceptibility genes may contribute to the development of FPC in the absence of somatic KRAS-activating mutation. Genetic testing for a wider variety of FPC-predisposition genes could provide better screening approach for high-risk groups of pancreatic cancer.

AIM The underlying mechanism of non-obese non-alcoholic fatty liver disease (NAFLD) has not been fully elucidated. We classified patients with NAFLD by sex and body mass index and compared their clinical features to clarify the background pathophysiology of non-obese NAFLD. METHODS A total of 404 patients with NAFLD were divided according to their body mass index (

To date, postoperative prognostic factors for intraductal papillary neoplasm of the bile duct (IPNB) have not been well-established. This study aimed to examine the histopathologic features and postoperative prognosis of the two IPNB subclassifications, as well as factors affecting prognosis, based on the authors’ experience at a single institution. The study enrolled 83 patients who underwent surgical resection for pathologically diagnosed IPNB at the authors’ institution. The clinicopathologic features and postoperative outcomes for these patients were examined. The study also investigated postoperative prognostic factors for IPNB using uni- and multivariate analyses. More than half of the tumors (64%) diagnosed as IPNB were early-stage cancer (UICC Tis or T1). However, none were diagnosed as benign. The multivariate analysis showed that lymph node metastasis (hazard ratio [HR], 5.78; p = 0.002) and bile duct margin status with carcinoma in situ (D-CIS; HR, 5.10; p = 0.002) were independent prognostic factors, whereas MUC6 expression showed only a marginal influence on prediction of prognosis (HR, 0.32; p = 0.07). The tumor recurrence rate and the proportion of locoregional recurrence were significantly greater among the patients with D-CIS than among those with negative bile duct margins, including those patients with low-grade dysplasia. The patients with D-CIS showed a significantly poorer prognosis than those with negative bile duct margins (5-year survival, 38% versus 87%; p = 0.0002). Evaluation of resected IPNBs showed cancer in all cases. Avoiding positive biliary stumps during surgery, including resection of carcinoma in situ, would improve the prognosis for patients with IPNB.

Comorbidity and relative dose intensity (RDI) have been associated with survival in diffuse large B-cell lymphoma (DLBCL) patients, but both relationships remain unaddressed in the same patients. A retrospective review of consecutive DLBCL patients treated from January 2010 to October 2018 was performed. Data for the clinical characteristics of the patients, including the Charlson Comorbidity Index (CCI) and RDI, on their outcomes were evaluated. A total of 211 patients with a median age of 72 years (range 19–90 years) were analyzed. CCI ≥ 2 was associated with poor event-free survival (EFS) and overall survival (OS). RDI

To collect large-scale 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 was initiated to collect data since 2014 and has already reported data including the prognostic data of 3820 patients newly diagnosed with CRLM between 2005 and 2007.The data of patients newly diagnosed with CRLM after 2013 are continuously being registered prospectively, and herein, we report the data of the patients newly diagnosed with CRLM in 2013 and 2014.The data of 3839 patients newly diagnosed with CRLM in 2013 and 2014 were registered from 156 departments (75%) of 152 institutions among 209 departments (from 201 institutions) that agreed to participate in this database system at its initiation. Finally, 3525 patients were enrolled in this study after a quality management process conducted by the joint committee. We report the comprehensive data obtained from 3525 patients, including clinicopathological findings, treatment strategies, and implementation status of chemotherapy.The joint committee will provide these raw data while updating prognostic data to researchers who will conduct meaningful studies that meet the aim of the joint committee.