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Effects of pancreatectomy on glucose tolerance have not been clarified, and evidence regarding the difference in postoperative glucose tolerance between pancreaticoduodenectomy (PD) and distal pancreatectomy (DP) is lacking.This prospective, single-center observational study analyzed 40 patients undergoing PD and 29 patients undergoing DP (Clinical trial registry number UMIN000008122). Glucose tolerance, including insulin secretion (Δ C-peptide immunoreactivity, ΔCPR) and insulin resistance (homeostasis model assessment of insulin resistance, HOMA-IR) were assessed before and 1 month after pancreatectomy using the oral glucose tolerance test (OGTT) and glucagon stimulation test. We assessed long-term hemoglobin A1c (HbA1c) levels in patients, with a follow-up time of 3 years.Percentages of patients diagnosed with abnormal OGTT decreased after PD (from 12 [30%] to 7 [17.5%] of 40 patients, p = 0.096); however, they increased after DP (from 4 [13.8%] to 8 [27.6%] of 29 patients, p = 0.103), although the changes were not statistically significant. ΔCPR decreased after both PD (from 3.2 to 1.0 ng/mL, p0.001) and DP (from 3.3 to 1.8 ng/mL, p0.001). HOMA-IR decreased after PD (from 1.10 to 0.68, p 0.001), but did not change after DP (1.10 and 1.07, p = 0.42). Median HbA1c level was higher after DP than after PD for up to 3 years, but the differences were not statistically significant.In comparisons of pre- and 1 month post-pancreatectomy data, glucose tolerance showed improvement after PD, whereas it worsened after DP. Insulin secretion decreased after both PD and DP. Insulin resistance improved after PD, but did not change after DP. Further studies are warranted to clarify mechanisms of improved insulin resistance after PD.

Background The clinical characteristics of IgG4-related sclerosing cholangitis (IgG4-SC) especially without autoimmune pancreatitis (AIP) have not been investigated in a large cohort. Aims To clarify the clinical characteristics of IgG4-SC and IgG4-SC without AIP. Methods We retrospectively reviewed imaging, serology, other organ involvement (OOI) and histology of 872 patients with IgG4-SC who participated in a Japanese nationwide survey in 2019, and compared these items between IgG4-SC with and without AIP. Results AIP was present in 83.7% (730/872) of IgG4-SC. In IgG4-SC, bile duct wall thickening was observed on ultrasound (528/650; 81.2%), computed tomography (375/525; 71.4%) and magnetic resonance imaging or cholangiopancreatography (290/440; 65.9%). An elevated serum IgG4 level (≥ 135 mg/dL) was found in 88.0% (322/366). IgG4-related OOI other than AIP was observed in 25.2% (211/836). The proportion of females was significantly higher in IgG4-SC without AIP (28.9% vs. 20.1%; p = 0.025). Hilar stricture was the most common cholangiographic type in IgG4-SC without AIP (39/107; 36.4%).There were no significant differences between IgG4-SC with and without AIP in the rates of bile duct wall thickening, elevated serum IgG4 level, or IgG4-related OOI. Conclusions The clinical characteristics of IgG4-SC was similar between IgG4-SC with and without AIP in a large cohort.

Background/aim Few studies have established a definite conclusion regarding the limitation of surgical treatment for patients with Barcelona Clinic Liver Cancer (BCLC) stage B and C hepatocellular carcinoma (HCC). Patients and methods A retrospective analysis was performed on 717 consecutive patients who underwent initial hepatectomy for HCC. Results Reductive hepatectomy was performed in 103 patients, with a median survival time (MST) of 18.0 months. Total bilirubin and albumin levels were identified as independent prognostic factors. The predictive score of these factors ranged from 0 to 2. Subsequent local treatment was performed in 91.0, 75.0, and 25.0% of patients who scored 0, 1, and 2, respectively. The MST for patients with a score of 0, 1, and 2 was 20.1, 14.8, and 2.7 months, respectively, with a significant difference. Conclusion Patients with BCLC stage B and C could be properly treated with reductive hepatectomy and subsequent local treatments.

Purpose This study retrospectively investigated relationships among risk factors and post-hepatectomy surgical site infection (SSI) and other complications in patients who underwent hepatectomy for hepatocellular carcinoma (HCC). Methods We included 334 patients who underwent hepatectomies for liver cancers between January 2011 and December 2015 in this study. We evaluated risk factors for SSI and other post-hepatectomy complication, including demographic factors, preoperative factors, and preoperative intervention including oral management, perioperative factors, and length of hospital stay, with univariate and multivariate analyses. The oral management intervention included self-care instructions, extraction of infected teeth, removal of dental plaques and calculus (scaling), professional mechanical teeth cleaning, removal of tongue coating, and cleaning of dentures. SSI was defined in accordance with the guideline issued by the Centers for Disease Control and Prevention; it included purulent discharge from any incision or organ space within 30 days postoperatively, with or without microbiological evidence. Complications of grade II or greater, according to the Clavien-Dindo classification, were regarded as postoperative complications. Results We found bacterial infection of ascites (Odds ratio (OR) = 13.72), lack of preoperative oral management intervention (OR = 10.17), and severe liver fibrosis (OR = 2.76) to be associated with SSI and severe liver fibrosis (OR = 2.28), hypoalbuminemia (OR = 2.02), blood transfusion (OR = 1.86), and longer operation time (OR = 1.80) to be associated with postoperative complications. Conclusions Preoperative oral management may reduce the risk of SSI in patients with HCC who undergo hepatectomy.

Background Particle radiotherapy has increasingly gained acceptance for locally advanced pancreatic cancers owing to superior tumor conformity and dosimetry compared to conventional photon radiotherapy. However, the close proximity of the pancreas to the stomach and duodenum leads to radiation-induced gastrointestinal toxicities, which hinder the delivery of curative doses to the tumor. To overcome this problem, a surgical spacer was placed between the tumor and gastrointestinal tract, and subsequent proton radiotherapy was performed in this study. Methods Data from 9 patients who underwent surgical spacer placement and subsequent proton radiotherapy were analyzed. The safety and feasibility of the spacer placement surgery were evaluated; the impact of the spacer on dosimetry was also assessed using dose volume histogram (DVH) analyses, before and after surgical spacer placement. Results Surgical spacer placement and subsequent proton radiotherapy were successfully completed in all cases. Surgical spacer placement significantly improved the dose intensity covering 95%, mean, and minimum doses for the gross tumor volume, and the clinical and planning target volume based on the DVH, while respecting the dose constraints of the gastrointestinal tract. Based on the Common Terminology Criteria for Adverse Events, two patients (22.2%) developed gastrointestinal ulcer (Grade 2) at 1 and 35 months, and one patient (11.1%) developed gastric perforation (Grade 4) at 4 months after proton radiotherapy. Conclusions Surgical spacer placement in the locally advanced pancreatic body and tail cancers is relatively safe and technically feasible. Comparing radiation plans, surgical spacer placement seems to improve the dose distribution in the locally advanced pancreatic body and tail cancers, which are close to the gastrointestinal tract.

Background Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is associated with acute pancreatitis (AP) in some cases, however its causes have not been fully elucidated. We investigated the association of the incidence of AP with epithelial subtypes and pancreatic volume in IPMN. Methods This retrospective study included 182 consecutive surgically resected IPMN patients between January 2000 and December 2018. The relationship between the incidence of AP and epithelial subtypes of IPMN and pancreatic volume was investigated. Epithelial subtypes of IPMN were classified into gastric (G type: N = 116), intestinal (I type: N = 49), pancreatobiliary (PB type: N = 14), and oncocytic types (O type: N = 3). Pancreatic volume of the contrast-enhanced computed tomography scan was measured using Ziostation2 software. Histological pancreatic parenchymal atrophy was also evaluated. Results AP occurred more frequently in I-types (I-type vs. G-type, 22.4% [11/49] vs 3.4% [4/116], P = 0.003) and PB-types (PB type vs. G-type, 35.7% [5/14] vs. 3.4% [4/116], P = 0.007) in comparison with G-types, which constituted the majority of the resected IPMNs. AP occurred more frequently in I-type patients with high pancreatic volumes (I-type with high pancreatic volume vs. I-type with low pancreatic volume, 37.0% [10/27] vs. 4.7% [1/21], P = 0.02). However, histological atrophy did not show an additional influence on the association between the incidence of AP and epithelial subtypes. The elevation of serum pancreatic enzymes was not significantly related to epithelial subtypes. Conclusion Epithelial subtypes and the degree of pancreatic volume may be closely associated with the incidence of AP in IPMN.

Background/aim We aimed to investigate the dosimetric effects of a spacer placed between the pancreas and surrounding gastrointestinal structures in intensity-modulated radiation therapy (IMRT) planning to provide more effective radiation therapy for locally advanced pancreatic cancer (LAPC). Patients and methods Treatment planning was performed for six patients with LAPC based on computed tomography images without spacers and with 5-mm or 10-mm spacers virtually inserted under the supervision of a hepatobiliary pancreatic surgeon. The prescription dose was 63 Gy in 28 fractions. Results With the exception of one case of pancreatic head cancer, planning target volume receiving ≥95% of the prescribed dose (PTV V95) was achieved by 90% or more by inserting a spacer, and by 95% or more in all 3 cases of pancreatic body and tail cancer by inserting a 10-mm spacer. Conclusion IMRT with appropriate spacer placement may help provide high-dose treatment for LAPC and improve associated patient outcomes.

A 60-year-old male visited a previous hospital with upper abdominal pain. He was diagnosed with localized mild acute pancreatitis. Three months later, abdominal contrast-enhanced computed tomography showed focal parenchymal atrophy of the pancreas with distal pancreatic duct dilation. No obvious solid mass could be found at the site of the pancreatic duct stenosis on imaging examinations. Endoscopic retrograde pancreatography showed focal mild stenosis with distal pancreatic duct dilation in the tail of the pancreas. Carcinoma in situ of the pancreas was strongly suspected, especially based on the presence of focal atrophy of the pancreas around the site of stenosis of the main pancreatic duct and the distal pancreatic duct dilation. Laparoscopic distal pancreatectomy was performed. Histologically, high-grade pancreatic intraepithelial neoplasia was found in the epithelium of the stenotic main pancreatic duct and its branches. This case suggests that localized acute pancreatitis and focal atrophy of the pancreas with distal dilation of the pancreatic duct could be important clinical manifestations of pancreatic carcinoma in situ.

A 66-year-old Japanese man was referred to our hospital with multiple giant liver cysts. The cysts had already been detected as multiple 3-cm cysts with small nodules at another hospital 12 years prior to this presentation. The cysts were diagnosed as an intraductal papillary neoplasms of the bile duct (IPNB) occupying the right lobe of the liver. Extended right lobectomy was performed. Based on the pathological findings, the tumor was diagnosed to be an oncocytic-type IPNB with minimal invasion. This experience suggests that the progression of IPNBs occur relatively slowly. The present case might provide important information for understanding the natural history of IPNBs.

Background Liver transplantation is the most suitable treatment option available for end-stage liver disease. However, some patients require retransplantation, despite medical advances that have led to improved survival. We aimed to compile a definitive, nationwide resource of liver retransplantation data in Japan, seeking to identify the predictors of patient survival posttransplantation. Methods Questionnaires were sent to 32 institutions that had conducted 281 retransplantations before 2015. Results Among the 265 patients included in this study (142 pediatric cases), the average age at primary transplantation was 23 years, and retransplantation was performed after an average of 1468 days. The main indication for retransplantation was graft rejection (95 patients). Living-donor liver transplantation accounted for 94.7% of primary transplantations and 73.2% of retransplantations. Patient survival at 1, 3, or 5 years did not differ by type of transplantation but was better for pediatric (70.8%, 68.3%, and 60.1%, respectively) than for adult (57.2%, 50.4%, and 45.2%, respectively) recipients (P = 0.0003). Small-for-size syndrome, retransplantation within 365 days, and inpatient status at retransplantation were significant predictors of poor survival in pediatric cases. Retransplantation within 365 days and conditions warranting retransplantation were significant predictors of poor survival in adult patients. Conclusions In Japan, where >70% of retransplantations are performed using living donors, the indications and timing are different from those in previous reports from other countries, while maintaining comparable survival rates. Considering technical challenges, graft failure within 365 days should be thoroughly restricted to justify the use of living donor.

Background: Pancreaticoduodenectomy (PD) is a standardized strategy for patients with middle and distal bile duct cancers. The aim of this study was to compare clinicopathological features of bile duct segmental resection (BDR) with PD in patients with extrahepatic cholangiocarcinoma. Methods: Consecutive cases with extrahepatic cholangiocarcinoma who underwent BDR (n = 21) or PD (n = 84) with achievement of R0 or R1 resection in Kobe University Hospital between January 2000 and December 2016 were enrolled in the present study. Results: Patients who underwent PD were significantly younger than those receiving BDR. The frequency of preoperative jaundice, biliary drainage and cholangitis was not significantly different between the two groups. The duration of surgery was longer and there was more intraoperative bleeding in the PD than in the BDR group (553 vs. 421 min, and 770 vs. 402 mL; both PClavien-Dindo IIIa) were observed in the PD group (46% vs. 10%, P

Background Sacral chordomas are rare malignant bone tumors and are often very large for complete resection. Particle therapy for these tumors, which are adjacent to the gastrointestinal tract, is restricted because the tolerance dose of the intestine is low. This study aimed to demonstrate the technical aspects and treatment results of space-making particle therapy with surgical spacer placement for sacral chordoma. We aimed to investigate the dosimetric change in the particle therapy before and after spacer placement and the safety, efficacy, and long-term outcomes of space-making particle therapy. Study Design Twenty-one patients with sacral chordomas who were excluded from typical particle therapy were enrolled between 2007 and 2015. Gore-Tex sheets (WL Gore & Assoc) were folded and placed between the sacral and rectum. Particle therapy with 70.4 Gy (relative biologic effectiveness) was then performed. Results The mean volume that allows 95% of the treatment plan dose of the gross tumor volume and clinical tumor volume after spacer placement was improved to 97.7% and 96.4% from preoperative values of 91.0% and 89.5%, respectively. The recurrence rate within the gross tumor volume was only 4.8%. The 4-year local progression-free survival rate was 68.4%. The 5-year overall survival rate was 100% and the adverse events were acceptable. Conclusions Considering improvements in the dose-volume histogram after spacer placement, low recurrence rates within the gross tumor volume, good survival rates, and low incidences of side effects, treatment of sacral chordoma with space-making particle therapy shows promise.

Background Factors associated with long-term survival in gemcitabine-concurrent proton radiotherapy (GPT) for non-metastatic, locally advanced pancreatic cancer (LAPC) remain unclear. This study aimed to determine the factors associated with long-term survival in GPT for non-metastatic LAPC. Methods The medical records of 123 patients with LAPC treated with GPT between February 2009 and December 2019 at Hyogo Ion Beam Medical Center were retrospectively reviewed to assess the factors associated with long-term survival outcomes. Results The median overall survival of the total cohort treated with GPT was 18.7 months. The 1- and 2-year overall, local progression-free, and progression-free survival rates were 70.4% and 35.7%, 78.2% and 59.0%, and 38.6% and 20.8%, respectively. Multivariate analysis revealed that LAPCs at the pancreatic body-tail and those without anterior peripancreatic invasion were independently associated with longer overall survival (P = 0.040 and P = 0.015, respectively). The median overall survival of patients with LAPC at the pancreatic body-tail and those with LAPC without anterior peripancreatic invasion were 24.1 and 28.1 months, respectively. LAPCs at the pancreatic body-tail had a higher volume ratio irradiated over 60 Gy equivalents at gross tumor volume than those at the pancreatic head (P P = 0.039). Conclusions GPT is a promising treatment option for patients with LAPC at the pancreatic body-tail and those with LAPC without anterior peripancreatic invasion.

Background Hepatocellular carcinoma (HCC) with major portal vein tumor thrombus (Vp4 PVTT) is an extremely advanced tumor with limited treatment options. Systemic chemotherapy is the only recommended treatment option, and atezolizumab plus bevacizumab has recently emerged as a first-line treatment option. Case presentation We describe the case of an 82-year-old man with unresectable advanced HCC with Vp4 PVTT who achieved a significant response to atezolizumab plus bevacizumab treatment. A single administration of atezolizumab plus bevacizumab ensured significant anti-tumor effects (regression in the tumor size and PVTT, portal vein recanalization, and serum alfa-fetoprotein levels decreased from 90,770 to 89 ng/mL). The patient continued with atezolizumab monotherapy, and after nine consecutive regimens, there was no apparent sign of residual tumor. Conclusions This case demonstrates the powerful anti-tumor effect of atezolizumab plus bevacizumab treatment for advanced HCC with Vp4 PVTT, suggesting that these agents can be a promising treatment option for such refractory tumors.

The prognosis of hepatocellular carcinoma (HCC) presenting with inferior vena cava tumor thrombus (IVCTT) is extremely poor. The aim of this study was to reveal the postoperative course and to identify patients who have survived surgical hepatectomy among HCC patients with IVCTT. Between January 2006 and December 2018, 643 patients underwent surgical hepatectomy for HCC at Kobe University Hospital. Among them, 20 patients were categorized as Vv3 according to the Japanese staging system. We retrospectively collected detailed data on these patients. The statistical, clinical, and pathological data were recorded prospectively and analyzed retrospectively. The median survival time was 9.8 months. Among all patients, 11 (55%) achieved R0 resection, and only two survivors were from this group. The number of tumors (solitary vs. multiple; p=0.050) and pathological Vp (pVp0 vs. other; p=0.009) were identified as risk factors for overall survival in the univariate analysis. In the multivariate analysis, pathological Vp (pVp0 vs. other; p=0.037) was identified as a significant prognostic factor for survival. Pathological Vp affected overall survival among IVCTT patients; the median survival time was 53.7 months with pVp0, 10.2 months with pVp1, and 8.8 months with pVp2–4 (p=0.035). For patients with IVCTT, surgical hepatectomy should be indicated only for those who do not have portal vein invasion and could achieve R0 resection.

OBJECTIVE To investigate the diagnostic performance of the extracellular volume (ECV) fraction in multiphasic contrast-enhanced computed tomography (CE-CT) for estimating histologic pancreatic fibrosis and predicting postoperative pancreatic fistula (POPF). METHODS Eighty-five patients (49 men; mean age, 69 years) who underwent multiphasic CE-CT followed by pancreaticoduodenectomy with pancreaticojejunal anastomosis between January 2012 and December 2018 were retrospectively included. The ECV fraction was calculated from absolute enhancements of the pancreas and aorta between the precontrast and equilibrium-phase images, followed by comparisons among histologic pancreatic fibrosis grades (F0‒F3). The diagnostic performance of the ECV fraction in advanced fibrosis (F2‒F3) was evaluated using receiver operating characteristic curve analysis. Multivariate logistic regression analysis was used to evaluate the associations of the risk of POPF development with patient characteristics, histologic findings, and CT imaging parameters. RESULTS The mean ECV fraction of the pancreas was 34.4% ± 9.5, with an excellent intrareader agreement of 0.811 and a moderate positive correlation with pancreatic fibrosis (r = 0.476; p

Background/aim While there is increasing evidence supporting the role of several first- and second-line treatment regimens for advanced hepatocellular carcinomas (HCC), the clinical relevance of rechallenge treatment with previously administered drugs, however, remains to be explored. Patients and methods Five consecutive patients with advanced HCC who received lenvatinib rechallenge treatment after ramucirumab were assessed. Results All patients were clinically diagnosed with failure after ramucirumab treatment, and the frequencies of ramucirumab administration before lenvatinib re-administration ranged from 3 to 11. The alfa-fetoprotein level in four of five patients decreased 1 month after the lenvatinib rechallenge. Radiological findings via the modified Response Evaluation Criteria in Solid Tumors showed stable diseases in four patients and a partial response in one. Conclusion Rechallenge treatment with lenvatinib after ramucirumab can be effective, and may be a treatment option for HCC in cases wherein the disease progressed after an initial response to lenvatinib treatment.

A 68-year-old man who had undergone distal gastrectomy for gastric cancer 3 years previously, presented to our hospital for examination of dilatation of the main pancreatic duct on follow-up computed tomography and magnetic resonance cholangiopancreatography. After examination, he was diagnosed with early-stage pancreatic cancer and distal pancreatectomy (DP) was planned. With informed consent, we performed indocyanine green (ICG) fluorography during DP and digital subtraction angiography (DSA) of vessels supplying the remnant stomach immediately before and after DP. On ICG fluorography, the remnant stomach gradually became fluoresced starting at the area of the lesser curvature, and the fluorescence eventually intensified over the entire area of the remnant stomach to the same brightness as that of the liver and duodenum. On DSA following DP, the terminal branches of the left inferior phrenic artery (LIPA) were distributed to more than half of the area of the remnant stomach, centering around the proximal area. It is useful to confirm blood flows to the remnant stomach by ICG fluorography using a near-infrared imaging camera during DP. We found that the LIPA played an important role in maintaining the blood supply to the remnant stomach in the absence of the left gastric artery and splenic artery.

Background The use of surgical metal clips is crucial for ligating vessels in various operations. The currently available metal clips have several drawbacks; they are permanent and interfere with imaging techniques such as computed tomography (CT) or magnetic resonance (MR) imaging and carry the potential risk of endo-clip migration. We recently developed a novel magnesium (Mg) alloy for biodegradable clips that reduces artifacts on CT imaging. This study aimed to examine the tolerance, biodegradability, and biocompatibility of the Mg alloy clips compared with those of standard titanium (Ti) clips in hepatectomy. Methods Thirty Wistar rats were divided into two groups based on the clip used (groups A and B). The vascular pedicle, including hepatic artery, portal vein, bile duct, and hepatic vein of the left lateral lobe, was ligated with the Ti clip in group A or the Mg alloy clip in group B, and then the left lateral lobe was removed. The rats were sacrificed at 1, 4, 12, 24, and 36 weeks after surgery. Clinical and histological evaluations were performed. Absorption rate was calculated by measuring the clip volume. Results Although the Mg alloy clips showed biodegradability over time, there were no significant differences in the serum concentration of Mg between the two groups. The remaining volume ratio of Mg alloy clips was 95.5, 94.3, 80.0, 36.2, and 16.7% at 1, 4, 12, 24, and 36 weeks, respectively. No side effects occurred. Most of the microscopic changes were similar in both groups. Conclusions The new biodegradable Mg alloy clips are safe and feasible in vessel ligation for hepatectomy in a rat model and reduce artifacts in CT imaging compared with the standard Ti clips.

AIMS The present study aimed to systematically compare clinicopathological and genetic features between keratin 19 (K19)-expressing hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). METHODS AND RESULTS Consecutive cases of HCC (n = 430) were classified into K19+ and K19- using immunohistochemistry. ICCA cases were also separated into small-(S-iCCA; n = 36) and large-duct types (n = 22) based on recently proposed criteria, with the former being used in the present study. Mutational hot-spots in TERT, CTNNB1, KRAS and IDH1 were sequenced. Twenty-six cases (6%) of HCC expressed K19. K19+ HCC was more strongly associated with chronic hepatitis B than K19- HCC and S-iCCA (46% versus 17% and 6%; both P

AIMS To investigate whether genetic or inflammatory pro-oncogenic factors are relevant to the increased risk of gallbladder cancers in patients with pancreaticobiliary maljunction (PBM). METHODS AND RESULTS Mutations in KRAS exon 2 were examined by a highly sensitive, droplet digital PCR platform using surgically resected specimens of PBM-associated (n = 31) and non-associated gallbladder cancers (n = 49). The tissue expression of IL-6 and IL-33, which are suspected to promote biliary carcinogenesis, was analysed by quantitative real-time PCR and in-situ hybridisation. The incidence of KRAS mutations was similarly low in PBM-associated (five of 32 cases; 16%) and non-associated cancers (four of 49 cases; 8%) (P = 0.272). The tissue expression of IL-33 mRNA, but not IL-6 mRNA, was significantly higher in PBM-associated gallbladder cancers than in gallbladder cancers without PBM (P = 0.004). A similar degree of IL-33 overexpression was also observed in the background non-cancerous mucosa in cases of PBM-associated gallbladder cancers, and was significantly greater than that in PBM cases with cholecystitis alone (P

This study aimed to evaluate the clinical relevance of hepatectomy for Barcelona Clinic Liver Cancer (BCLC) stages B and C advanced hepatocellular carcinoma (HCC). A total of 314 patients (149 and 165 BCLC stages B and C, respectively) who underwent hepatectomy were included. Complete hepatectomy (without residual tumors after hepatectomy) and reductive hepatectomy (apparent residual tumors after hepatectomy) were performed for 212 and 102 patients, respectively. Short-term operative and postoperative outcomes, as well as long-term outcomes, were evaluated. The median survival times of patients with stage B disease undergoing complete hepatectomy and reductive hepatectomy were 48.9 and 20.1 months, respectively (p = 0.0075), whereas those of patients with stage C disease were 19.5 and 17.6 months, respectively (p = 0.0140). The 3-year overall survival rates of patients with stage B disease undergoing reductive hepatectomy with and without subsequent local treatments after surgery were 47.5% and 0%, respectively, whereas those of patients with stage C diseases were 18.6% and 0%, respectively. Survival benefits are obvious for both BCLC stages B and C HCC when complete hepatectomy can be performed safely. Reductive hepatectomy is also acceptable for BCLC stages B and C when subsequent local treatment for remnant liver tumors can be performed safely after reductive hepatectomy. Without subsequent local treatment, reductive hepatectomy has little clinical relevance. Thus, a cautious approach to patient selection is required for this aggressive strategy.

Although intracholecystic papillary neoplasms (ICPNs) have been increasingly recognized, their features remain unclear because of the lack of standardized definition. This study aimed to elucidate clinicopathologic and genetic features of ICPNs using stringent diagnostic criteria. On the basis of the recently proposed criteria, gallbladder neoplasms showing delicate papillary growth were diagnosed as ICPNs, while polypoid papillary adenocarcinomas arranged in a complex architecture were categorized as papillary gallbladder cancers (GBCs). Clinicopathologic features were compared among ICPNs (n=7), papillary GBCs (n=24), and nonpapillary GBCs (n=44). Whole-exome and validation Sanger sequencing was also conducted. Gross mucin hypersecretion was detected in 3/7 ICPNs (43%), 1/24 papillary GBCs (4%), and 1/44 nonpapillary GBCs (2%) (P

Background Growing evidence has suggested that intrahepatic cholangiocarcinoma (iCCA) can be classified into small- and large-duct types. The present study aimed to elucidate how large-duct iCCA is similar and dissimilar to perihilar cholangiocarcinoma (pCCA). Methods The study cohort consisted of iCCA (n = 58) and pCCA (n = 44). After iCCA tumors were separated into small- (n = 36) and large-duct (n = 22) types based on our histologic criteria, genetic statuses of the three types of neoplasms were compared. Locations of iCCA were plotted on a three-dimensional image and their distances from the portal bifurcation were measured. Results Large-duct iCCA was distinct from small-duct iCCA in terms of frequency of bile duct reconstruction required, perineural infiltration, and survival, with these features more similar to pCCA. Large-duct iCCA and pCCA more frequently had the loss of SMAD4 expression and MDM2 amplifications than small-duct iCCA, whereas the loss of BAP1 expression and IDH1 mutations were mostly restricted to small-duct iCCA. From imaging analysis, most tumors of large-duct iCCA were present around the second branches of the portal vein. Conclusion Large-duct type iCCA shared the molecular features with pCCA, and it may be reasonable to expand the definition of pCCA to include cancers originating from the second bile duct branches.

Objective This study aimed to determine whether retrocolic alimentary tract reconstruction is noninferior to antecolic reconstruction in terms of DGE incidence after pancreatoduodenectomy (PD) and investigated patients' postoperative nutritional status. Summary of background data The influence of the route of alimentary tract reconstruction on DGE after PD is controversial. Methods Patients from 9 participating institutions scheduled for PD were randomly allocated to the retrocolic or antecolic reconstruction groups. The primary outcome was incidence of DGE, defined according to the 2007 version of the International Study Group for Pancreatic Surgery definition. Noninferiority would be indicated if the incidence of DGE in the retrocolic group did not exceed that in the antecolic group by a margin of 10%. Patients' postoperative nutrition data were compared as secondary outcomes. Results Total, 109 and 103 patients were allocated to the retrocolic and antecolic reconstruction group, respectively (n = 212). Baseline characteristics were similar between both groups. DGE occurred in 17 (15.6%) and 13 (12.6%) patients in the retrocolic and antecolic group, respectively (risk difference; 2.97%, 95% confidence interval; -6.3% to 12.6%, which exceeded the specified margin of 10%). There were no differences in the incidence of other postoperative complications and in the duration of hospitalization. Postoperative nutritional indices were similar between both groups. Conclusions This trial could not demonstrate the noninferiority of retrocolic to antecolic alimentary tract reconstruction in terms of DGE incidence. The alimentary tract should not be reconstructed via the retrocolic route after PD, to prevent DGE.

This study aims to validate Japanese diagnostic criteria for acute-on-chronic liver failure (ACLF) and confirm the feasibility of performing transplantation.We included 60 patients with acute liver injury. Demographic and clinical features were retrospectively collected, and the primary outcome was compared among 4 types: acute liver failure (ALF) with hepatic coma (n = 23), ALF without hepatic coma (n = 12), acute liver injury (n = 20), and ACLF (n = 5). Moreover, 80 transplanted patients were enrolled to compare the difficulty of transplantation between ALF (n = 8) vs non-ALF (n = 72) patients.Seven patients in the ALF with hepatic coma group and 1 patient in the ACLF with hepatic coma group were transplanted. Ten patients who could not be registered for transplantation died. In univariate analysis, liver failure type (P.0001), total bilirubin level (P = .05), and prothrombin time internationalized ratio (P.0001) were associated with patient survival. In multivariate analysis, liver failure type was associated with patient survival (P.0001). The respective 1-, 3-, and 5-year patient survival rates were 45.9%, 45.9%, and 45.9% for ALF patients with hepatic coma; 100.0%, 100.0%, and 100.0% for ALF patients without hepatic coma and acute liver injury; and 80.0%, 80.0%, and 80.0% for ACLF patients (P.0001). Chronic liver disease did not affect operation time (P = .46) and bleeding volume (P = .49).Patients diagnosed with ACLF via Japanese criteria presented significantly higher survival rates than ALF patients with hepatic coma.

Several studies comparing internal and external stents have been conducted with the aim of reducing pancreatic fistula after PD. There is still no consensus, however, on the appropriate use of pancreatic stents for prevention of pancreatic fistula. This multicenter large cohort study aims to evaluate whether internal or external pancreatic stents are more effective in reduction of clinically relevant pancreatic fistula after pancreaticoduodenectomy (PD).We reviewed 3149 patients (internal stent n = 1,311, external stent n = 1838) who underwent PD at 20 institutions in Japan and Korea between 2007 and 2013. Propensity score matched analysis was used to minimize bias from nonrandomized treatment assignment. The primary endpoint was the incidence of clinically relevant pancreatic fistula. This study was registered on the UMIN Clinical Trials Registry (UMIN000032402).After propensity score matched analysis, clinically relevant pancreatic fistula occurred in more patients in the external stents group (280 patients, 28.7%) than in patients in the internal stents group (126 patients, 12.9%) (OR 2.713 [95% CI, 2.139-3.455]; P 0.001). In subset analysis of a high-risk group with soft pancreas and no dilatation of the pancreatic duct, clinically relevant pancreatic fistula occurred in 90 patients (18.8%) in internal stents group and 183 patients (35.4%) in external stents group. External stents were significantly associated with increased risk for clinically relevant pancreatic fistula (OR 2.366 [95% CI, 1.753-3.209]; P 0.001).Propensity score matched analysis showed that, regarding clinically relevant pancreatic fistula after PD, internal stents are safer than external stents for pancreaticojejunostomy.

Survival after surgery for pancreatic adenocarcinoma (PA) is poor and heterogeneous, even for curative (R0) resection. Serum carbohydrate antigen (CA) 19-9 levels are important prognostic markers for resected PA. However, sustained elevation of CA19-9 in association with the patterns of recurrence has been rarely investigated. Patients who underwent R0 resection (n = 539) were grouped according to postoperative serum CA19-9 levels (Group E: sustained elevation; Group N: no elevation). Clinicopathological factors, patterns of recurrence, and survival were compared between the groups. Group E (n = 159) had significantly shorter median overall survival (17.1 vs. 35.4 months, p

Metallic medical devices are typically constructed from non-bioabsorbable metals that remains in the body and causes considerable complications. Particularly in the urinary tract, calculus, intractable infection, and misdiagnosis as calculus are often caused by non-bioabsorbable metals. Here, we developed a zinc–magnesium alloy as a new bioabsorbable metal and sought to evaluate the bioabsorbable behavior of zinc and zinc–magnesium alloy in a rat bladder implantation model. We prepared zinc–magnesium alloy wires with various proportions of magnesium and investigated the strength, shape retention, formability, and absorbability of these novel materials. Then, we implanted zinc and zinc–magnesium alloy rings formed by the wires into rat bladder. Rats were euthanized at the end of the observation period, and the rings were removed for volume evaluation. Extracted bladder tissues were subjected to histological analysis. The strength of the zinc wire was enhanced by more than fourfold upon the addition of magnesium, without loss of ductility. Linear reduction of ring volume in urine was observed based on the concentration of magnesium within the ring. Nearly all rings were covered with a thin layer of calculus. Histological findings of the transected urinary bladder tissues did not differ among groups. Zinc–magnesium alloy is a promising candidate for use as a bioabsorbable medical device in the urinary tract.

Background: This study evaluated the prognosis of hepatocellular carcinoma (HCC) patients with extrahepatic metastases who can undergo hepatectomy. Methods: A total of 32 patients who underwent hepatectomy for HCC with extrahepatic metastases, including lymph node and/or distant metastases were recruited for this study. Results: Fourteen patients had lymph node metastasis only, 16 had distant metastasis only, and 2 had both metastasis types during preoperative diagnosis. The 3-year overall survival (OS) rate of all patients was 17.9%, and the median survival time (MST) was 11.8 months. Univariate analysis revealed that intrahepatic maximal tumor size, intrahepatic tumor number, and intrahepatic tumor control after hepatectomy were significant factors influencing OS (p < 0.05). Multivariate analysis revealed that independent risk factors for OS were intrahepatic maximal tumor size and intrahepatic tumor number (p < 0.05). The MST and 3-year OS rate of patients with maximal tumor size Conclusions: Hepatectomy is not recommended for HCC patients with extrahepatic metastasis with ≥3 intrahepatic tumors, even when all intrahepatic tumors can be eliminated via hepatectomy. Aggressive surgery may be justified for HCC patients with ≤2 intrahepatic tumors and maximal tumor size

The prognostic impact of pancreatic ductal adenocarcinoma (PDAC) invasion to the splenic vessel is controversial. The aim of this study was to assess the clinical value of pathological and radiological splenic vessel invasion in PDACs of the body and tail. Medical records of patients with resectable PDAC of the body and tail who underwent distal pancreatectomy between 2003 and 2016 at the Kobe University Hospital were retrospectively analyzed. Overall, 68 patients (29 female and 39 male patients) were enrolled. Pathologically determined splenic vein invasion (p-SV) and splenic artery invasion (p-SA) were identified in 21 (30.9%) and 5 (7.4%) patients, respectively. The p-SV (but not p-SA) was an independent prognostic factor in multivariate analysis (p = 0.009). On analysis of recurrence patterns, patients with PDAC positive for p-SV were at a higher risk for liver metastasis (p = 0.022); however, the associations were not significant for other recurrence patterns. Liver metastasis occurred earlier in patients who were positive for p-SV (p = 0.015). Preoperative computed tomography effectively diagnosed pathological vessel invasion (SV: sensitivity, 95.2%, specificity, 72.3%; SA: sensitivity, 100%, specificity, 84.1%). Radiological SV invasion remained significant in multivariate analysis regarding postoperative survival (p = 0.007), and was also associated with early liver metastases (p = 0.008). Pathological/radiological SV invasion were independent adverse prognostic factors associated with early liver metastasis in patients with PDAC of the body/tail. Assessment of these findings may be useful in determining optimal therapeutic options in these patients.

The safety and efficacy of reinforced staplers during distal pancreatectomy (DP) remain controversial because of the small sample size. This multicenter single-arm prospective study aims to evaluate the safety and efficacy of reinforced staplers with bioabsorbable material during DP. Between October 2014 and August 2015, 121 patients scheduled for DP were enrolled in this study at 11 institutions in Japan. The primary endpoint was the incidence of clinically relevant pancreatic fistula. Protocol treatment was defined as “distal pancreatectomy using reinforced staplers.” Per-protocol analysis of 105 patients was performed; 16 of the patients were excluded based on discontinuation of protocol treatment criteria. Clinically relevant pancreatic fistula occurred in 13 (12.4%) of 105 patients. The overall morbidity rate was 29.5% (31 of 105 patients) and severe complication (Clavien classification IIIa or more) was 10.5% (11/105). Mortality rate was 0%, although reoperations were performed on two patients (1.9%). Multivariate logistic regression analysis of independent risk factors for clinically relevant pancreatic fistula after DP using reinforced stapler closure was operative time more than 240 min (P = 0.047, odds ratio 5.79), registration numbers less than 10 (P = 0.046, odds ratio 13.01), and staple line hemorrhage (P = 0.003, odds ratio 16.34). This study confirms the safety of reinforced staplers for pancreatic stump closure during DP. However, the efficacy of reinforced staplers for decreasing clinically relevant pancreatic fistula could not be drawn from this study. This prospective study was registered with ClinicalTrials.gov (NCT02270554) and UMIN Clinical Trial Registry (UMIN000015384).

Iso- or hypo-attenuating areas in the arterial phase on contrast-enhanced computed tomography (CE-CT) have been reported to be negative prognostic features in pancreatic neuroendocrine tumors (PNETs). Given that the optimal indication for lymph node dissection in patients with PNET remains unclear, we sought to utilize enhancement characteristics on CE-CT as a preoperative predictor of regional lymph node metastasis in PNETs.The medical records of patients with well-differentiated PNETs who underwent pancreatectomy along with lymphadenectomy were retrospectively analyzed. We divided PNETs into two groups based on the extent of attenuation in the late arterial phase on CE-CT imaging. PNETs that showed hyper-attenuation over the entire area compared to the adjacent normal pancreas were categorized as hyper-PNETs. PNETs that contained both hyper and iso- or hypo-attenuation regions as well as those that showed only iso- or hypo-attenuation over the entire area were categorized as hetero/hypo-PNETs.Forty-one patients with a median age of 64 years were enrolled, including 11 with hyper-PNETs and 30 with hetero/hypo-PNETs. Hetero/hypo-PNETs were significantly larger than hyper-PNETs (P = 0.022), and the former group more frequently comprised G2 tumors, according to the World Health Organization 2010 classification (P 0.001). On univariate and multivariate analyses, hetero/hypo-PNETs were independently associated with regional lymph node metastasis.The presence of iso- or hypo-attenuating regions appears to be associated with regional lymph node metastasis in PNETs. Tumor enhancement characteristics should be assessed in patients with PNET so as not to miss those at high risk of lymph node metastasis.

Intrahepatic cholangiocarcinomas were classified into two types based on their microscopic appearance. Tumors with histologic similarities to hilar cholangiocarcinomas (predominantly ductal adenocarcinomas with minor tubular components, if present, restricted to the invasive front) were defined as the perihilar type, whereas the others were classified as peripheral cholangiocarcinomas. Among the 47 cases examined in the present study, 26 (55%) were classified as the perihilar type, whereas 21 (45%) were the peripheral type. The perihilar type had higher pT stages and more frequently showed a periductal-infiltrating gross appearance and microscopic perineural infiltration than peripheral cholangiocarcinomas. The presence of low-grade biliary intraepithelial neoplasia in the adjacent bile ducts was only found in perihilar cholangiocarcinomas (6/21, 29%). The immunophenotype also differed between the two types with MUC5AC and MUC6 being more commonly expressed in the perihilar type. One-third of perihilar cholangiocarcinomas lacked the expression of SMAD4, suggesting SMAD4 mutations, whereas the loss of BAP1 expression and IDH1 mutations were almost restricted to the peripheral type (35 and 15%, respectively). Patients with perihilar cholangiocarcinoma had worse overall survival than those with peripheral cancer (P=0.027). A multivariate analysis identified the histologic classification as an independent prognostic factor (P=0.005, HR=3.638). Comparisons between intrahepatic and hilar cholangiocarcinomas also revealed that the molecular features and prognosis of perihilar cholangiocarcinomas were very similar to those of hilar cholangiocarcinomas. In conclusion, this histology-based classification scheme of intrahepatic cholangiocarcinomas will be useful and clinically relevant because it represents different underlying molecular features and has an independent prognostic value.

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

It remains controversial whether preoperative cholangitis affects long-term outcomes after resection in patients with extrahepatic bile duct cancer. A total of 107 patients with extrahepatic bile duct cancer who underwent resection with curative intent from 2008 to 2014 were retrospectively reviewed. Patients were categorized into two groups according to the presence or absence of preoperative cholangitis. Clinicopathological variables and long-term outcomes were compared in the two groups. In the preoperative cholangitis group, the rate of preoperative biliary drainage, the number of tube changes and/or additions, and the rate of lymph node metastasis were higher compared to the no-cholangitis group. Overall survival and disease-free survival were significantly worse in the cholangitis group compared to the no-cholangitis group (p = 0.022, p = 0.007). A poorer prognosis was not observed with an increasing grade of cholangitis in Tokyo Guidelines 2013 (p = 0.09). A multivariate logistic regression analysis revealed that the preoperative cholangitis was an independent prognostic factor for extrahepatic bile duct cancer. Preoperative cholangitis is an independent prognostic factor in patients with extrahepatic bile duct cancer regardless of the severity of the cholangitis.

The present study aimed to elucidate whether the stemness molecule, CD133, is expressed in well-differentiated pancreatic neuroendocrine tumors (PanNETs; World Health Organization grades 1 and 2) and establish its clinical relevance using 2 separate cohorts. In the first series (n = 178) in which tissue microarrays were available, immunohistochemistry revealed that CD133 was expressed in 14 cases (8%). CD133+ PanNETs had higher TNM stages (P < .01), more frequent lymphovascular invasion (P = .01), and higher recurrence rates (P = .01). In the second cohort (n = 56), the expression of CD133 and CK19 was examined in whole tissue sections. CD133 and CK19 were positive in 10 (18%) and 36 (64%) cases, respectively. CD133 expression correlated with higher pT scores (P < .01), the presence of microscopic venous infiltration (P = .03), and shorter disease-free periods (P < .01). When cases were divided into grade 1 and 2 neoplasms, patients with CD133+ PanNET continued to have shorter disease-free periods than did those with CD133- tumors in both groups (P < .01 and P = .02, respectively). Although CK19+ cases had shorter disease-free periods than did CK19- cases in the whole cohort (P = .02), this difference was less apparent in subanalyses of grade 1 and 2 cases. CD133 expression also appeared to be an independent predictive factor for tumor recurrence in a multivariate analysis (P = .018). The CD133 phenotype was identical between primary and metastatic foci in 17 of 18 cases from which tissues of metastatic deposits were available. In conclusion, the combination of CD133 phenotyping and World Health Organization grading may assist in stratifying patients in terms of the risk of progressive clinical courses.

Background and aim Lymph node metastasis predicts poorer prognoses in patients with invasive intraductal papillary mucinous neoplasms of the pancreas (IPMNs). Factors associated with lymph node metastasis of invasive IPMN remain unclear. Therefore, this study aimed to define factors associated with lymph node metastasis of invasive IPMN. Methods Between June 2000 to August 2015, 156 consecutive patients with IPMN underwent surgical resection at Kobe University Hospital, and were enrolled in this study. The relationship between lymph node metastasis and clinical characteristics, including imaging studies and serum tumor markers, was evaluated. A multivariate logistic regression analysis was performed to assess the relationship between serum tumor markers and the presence of lymph node metastasis of IPMN, adjusted for clinical characteristics. Results Lymph node metastasis was observed in 7.7% (12/156) of IPMNs via a pathological examination. The multivariate logistic regression analysis revealed that serum SPan-1 was associated with the presence of lymph node metastasis of IPMN (odds ratio [OR] = 7.32; 95% confidence interval [CI] = 1.10 to 56.0; P = 0.04). In addition, survival was poorer among serum SPan-1-positive patients than SPan-1 negative patients (Log-rank test; P = 0.0002). Lymph node enlargement was detected preoperatively on computed tomography scans in only 16.7% (2/12) of cases that were positive for lymph node metastasis. Conclusions Elevated serum SPan-1 was associated with lymph node metastasis in this cohort of patients who underwent resection for invasive IPMN.

The biological behavior of well-differentiated neuroendocrine tumors of the pancreas (PNETs) is difficult to predict. This study was designed to determine whether involvement of the main pancreatic duct (MPD) serves as a poor prognostic factor for PNETs. The involvement of the MPD in PNETs was defined as ductal stenosis inside the tumor mass associated with distal MPDs more than twofold larger in diameter than the proximal ducts. We examined the correlation between MPD involvement and other clinicopathological parameters, including nodal metastasis and recurrence-free survival, in 101 patients treated consecutively at three referral centers in Japan. All patients underwent surgical resection. MPD involvement was observed in 13 of the 101 cases (13%) and was associated with multiple unfavorable clinicopathological features (e.g., larger tumor size, higher histological grade, more frequent nodal metastasis, and higher recurrence rates). Patients with MPD involvement also showed significantly worse recurrence-free survival than did those without ductal involvement (P

Aims Biliary intraductal tubular neoplasms that are non-mucinous and negative for mucin 5AC (MUC5AC) are called intraductal tubulopapillary neoplasms (ITPNs). Intraductal tubular neoplasms with mucinous cytoplasm and MUC5AC positivity also occur and their nature remains unclear, although some pathologists may classify these as 'intraductal papillary neoplasms of the bile duct (IPNBs) of gastric type'. This study aimed to elucidate genetic features of biliary intraductal tubular neoplasms. Methods and results Six resected cases of biliary intraductal neoplasm with >70% tubular configuration were characterised by clinicopathological examination and whole exome sequencing, and the findings obtained were compared between MUC5AC-negative (n = 2) and -positive cases (n = 4). The intraductal tumours consisted of the pancreatobiliary-type epithelium with high-grade dysplasia arranged in back-to-back tubules. Both of the two MUC5AC-negative cases were non-invasive neoplasms and developed in the liver, whereas all MUC5AC-positive cases had invasive carcinoma and were present in the intrahepatic (n = 2), perihilar (n = 1) and distal bile ducts (n = 1). In an exome-sequencing study, MUC5AC-negative cases harboured mutations in CTNNB1, SF3B1, BAP1 and BRCA1 (one case each). KRAS mutations were observed in three of four MUC5AC-positive cases (75%) but none of the MUC5AC-negative neoplasms. Compared to published data, known driver genes of other intraductal neoplasms of the pancreatobiliary system (e.g. APC, CTNNB1, STK11, GNAS and PIK3CA) were wild-type in all but one MUC5AC-negative case with CTNNB1 mutation. Chromatin modifiers (ARID1A, BAP1 and KMT2C) were also altered in MUC5AC-positive cases, similar to usual cholangiocarcinomas. Conclusions This exome-sequencing study suggested that MUC5AC-negative biliary ITPNs are genetically distinct from pancreatic ITPNs and IPNBs. They may also biologically differ from MUC5AC-positive tubular neoplasms despite morphological resemblance.

Background The albumin-bilirubin (ALBI) grade, stratified from the ALBI score, may have prognostic value in patients with hepatocellular carcinoma. We aim to evaluate the prognostic abilities of the ALBI score/grade among living-donor liver transplantation patients. Methods We retrospectively collected data of 81 patients who underwent living-donor liver transplant at Kobe University Hospital between June 2000 and October 2018. The efficacy of the ALBI score/grade as a prognostic factor was assessed and compared with that of the well-established Model for End-Stage Liver Disease (MELD) score. Main findings Multivariate analysis indicated that recipient age (P = .003), donor age (P = .003), ALBI score ≥ -1.28 (P = .002), and ALBI grade III (P = .004) were independently associated with post-transplant survival. A high MELD score was not associated with post-transplant survival in univariate or multivariate analyses. Although there was no significant difference in the overall survival rate relative to recipient and donor age, ALBI score/grade was significantly associated with the 1- and 5-year survival rates (P = .023, P = .005). ALBI scores specifically detected fatal complications of post-transplant graft dysfunction (P = .031) and infection (P = .020). Conclusion ALBI score/grade predicted patient survival more precisely than the MELD score did, suggesting that it is a more useful prognostic factor compared to the MELD score in living-donor liver transplantation cases.

BACKGROUND Acute cholecystitis (AC) after cardiovascular surgery (CS) tends to have a serious postoperative course; however, there are few reports of AC after CS. In this study, we investigated the clinical features of AC after CS. METHOD Of 26 patients who underwent surgery for AC after CS between 2001 and 2018 were investigated. Of these patients, the severity of AC, onset time, surgical outcomes, and postoperative pathological findings were evaluated. RESULTS Grade III accounted for 46% (12/26) of the AC after CS patients. Gallbladder drainage did not produce sufficient outcomes in all CS cases. The postoperative hospital days of AC after CS were extended (31/21 days, P = 0.07) and the postoperative pathologic findings revealed a higher rate of gangrenous cholecystitis (88/41%, P

IntroductionIn-vivo fluorescence imaging techniques using indocyanine green (ICG) to identify liver tumours and hepatic segment boundaries have been recently developed. The purpose of this study is to evaluate the efficacy of fusion ICG-fluorescence imaging for navigation during hepatectomy.Methods and analysisThis will be an exploratory single-arm clinical trial; patients with liver tumours will undergo hepatectomy using the ICG-fluorescence imaging system. In total, 110 patients with liver tumours scheduled for elective hepatectomy will be included in this study. Preoperatively, ICG will be intravenously injected at a dose of 0.5 mg/kg body weight within 2 days. To detect liver tumours intraoperatively, the hepatic surface will be initially observed using the ICG-fluorescence imaging system. After identifying and clamping the portal pedicle corresponding to the hepatic segments, including the liver tumours to be resected, additional ICG will be injected intravenously at a dose of 0.5 mg/kg body weight to identify the boundaries of the hepatic segments. The primary outcome measure will be the success or failure of the ICG-fluorescence imaging system in identifying hepatic segments. The secondary outcomes will be the success or failure in identifying liver tumours, liver function indicators, operative time, blood loss, rate of postoperative complications and recurrence-free survival. The findings obtained through this study are expected to help to establish the utility of ICG-fluorescence imaging systems, and therefore contribute to prognostic outcome improvements in patients undergoing hepatectomy for various causes.Ethics and disseminationThe protocol has been approved by the Kobe University Clinical Research Ethical Committee. The findings of this study will be disseminated widely through peer-reviewed publications and conference presentations.Trial registration numberUMIN000031054 and jRCT1051180070

Summary We recently experienced cases of pancreatobiliary-type intraductal papillary mucinous neoplasms (PB-IPMNs) with imaging features resembling pancreatic ductal adenocarcinomas (PDACs), and histologic appearance of purely pancreatobiliary morphology and highly distorted papillary growth, which led to the present study aiming to systematically investigate PB-IPMNs in comparison with PDACs. Surgical cases of PB-IPMNs (n = 31) and PDACs (n = 24) were examined. PB-IPMNs were classified into monotypic tumors (n = 12; 39%) consisting of entirely high-grade pancreatobiliary-type neoplastic cells and polytypic cases (n = 19; 61%) associated with components of low-grade dysplasia and/or other histologic types (eg, gastric, intestinal, or oncocytic types). Clinically, monotypic PB-IPMNs less commonly had dilatation of the ampullary orifice (0% versus 74%) and mucin hypersecretion (17% versus 89%) than did polytypic cases. In most cases of monotypic PB-IPMNs, cystic dilatation of the lesional ducts was less obvious on imaging; therefore, 33% were radiologically diagnosed as PDACs. Histologically, intraductal tumors in monotypic cases showed a highly complex papillary architecture with tubular/cribriform glands and irregular branching, and all these cases were associated with invasive malignancy. GNAS mutations were detected in polytypic PB-IPMNs (6/19; 32%), but there were no GNAS mutations in monotypic cases. The recurrence-free survival of patients with monotypic PB-IPMN or PDAC was similar and significantly worse than that of patients with polytypic PB-IPMN. In conclusion, some cases of monotypic PB-IPMNs lacked the classic characteristics of IPMNs and shared features with PDACs, raising the possibility that these cases may be better classified as a papillary variant of PDACs rather than IPMNs.

The patient was a 63-year-old man with hepatitis C. He discontinued combination therapy containing interferon and ribavirin because of the development of skin symptoms. A screening examination showed multiple early-stage hepatocellular carcinomas. He refused treatment and was followed up as an outpatient. During follow-up, his PIVKA-Ⅱ level remarkably elevated to 59,994mAU/mL. Computed tomography(CT)showed an enlarged tumor with portal invasion(vp2)in segment 8 and intrahepaticmetastasis. We performed right and partial hepatectomy. Three months later, CT showed multiple lung metastases. We initiated the daily administration of 800 mg of sorafenib. However, 6 months after hepatectomy, the lung metastases increased in size and number. We considered the therapeutic effect as progressive disease(PD)according to the RECIST criteria. We then initiated administering 120 mg of regorafenib daily as second-line therapy. In a course of the treatment containing sorafenib and regorafenib, the dose was reduced due to hand-foot skin reactions. 8.5 months after hepatectomy, the lung metastases significantly decreased in size. One year after hepatectomy, almost complete response(CR) was obtained, and no intrahepatic recurrence was found.

Background and aim Chronic pancreatitis is a risk factor for pancreatic cancer. Pancreatic calcification is a characteristic of chronic pancreatitis; however, its significance for intraductal papillary mucinous neoplasm (IPMN) oncogenesis remains unknown. Therefore, we investigated the relationship between pancreatic calcification and invasive IPMN. Methods This study included 157 patients who underwent resection for IPMN between April 2001 and October 2016 (intraductal papillary mucinous adenoma, n = 76; noninvasive intraductal papillary mucinous carcinoma [IPMC], n = 32; and invasive IPMC, n = 49). We divided the subjects on the basis of the presence/absence of pancreatic calcification on preoperative computed tomography (CT). The factors associated with pancreatic calcification were investigated in univariate analyses. Then, multivariate logistic regression analyses of the relationship between pancreatic calcification and invasive IPMC (after adjusting for clinical or imaging characteristics) were conducted. Results Preoperative CT revealed pancreatic calcification in 17.2% (27/157) of the resected IPMN. In the univariate analyses, jaundice, high serum carbohydrate antigen 19-9 levels, and invasive IPMC were significantly associated with pancreatic calcification (4/27 [14.8%] vs 4/130 [3.1%], 0.01; 12/27 [44.4%] vs 31/130 [23.8%], 0.03; and 15/27 [55.6%] vs 34/130 [26.2%], 0.001, respectively). Pancreatic calcification was significantly associated with invasive IPMC (multivariate odds ratio = 2.88, 95% confidence interval [95% CI] = 1.15-7.21, 0.03, adjusted for clinical characteristics; odds ratio = 5.50, 95% CI = 1.98-15.3, 0.001, adjusted for imaging characteristics). Conclusions Pancreatic calcification on CT is associated with invasive IPMC. Pancreatic calcification might be a predictor of invasive IPMC.

AIM To evaluate the clinical significance of lateral pelvic lymph node (LLN) size in predicting pathological metastasis and prognosis in rectal cancer treated with preoperative chemoradiotherapy (CRT) followed by surgery. PATIENTS AND METHODS Fifty-two patients with rectal cancer who underwent curative surgery after preoperative CRT were included. Fifteen patients underwent total mesorectal excision (TME) alone, while 37 patients underwent TME with LLN dissection for clinical LLN metastasis. RESULTS Pathological metastasis was identified in seven (2.6%) out of 270 resected LLNs in six (16.2%) out of 37 patients. The cut-off value of the short-axis diameter was 7.0 mm before and 6.0 mm after CRT. The 5-year recurrence-free survival rate was significantly higher in patients with LLNs

Aims The aim of this study was to achieve a better definition of intraductal papillary neoplasms of the bile duct (IPNBs). Methods and results Biliary tumours that showed predominantly intraductal papillary growth were provisionally classified as IPNBs (n = 25) and papillary cholangiocarcinomas (n = 27). IPNB was defined as a neoplasm that is confined to the epithelium or is regularly arranged in a high-papillary architecture along thin fibrovascular stalks, whereas the term ‘papillary cholangiocarcinoma’ was used for tumours with more complex papillary structures (e.g. irregular papillary branching or mixed with solid–tubular growth). In our consecutive cohort of biliary neoplasms, 5% were classified as IPNBs, and 10% as papillary cholangiocarcinomas. IPNBs differed from papillary cholangiocarcinomas by less advanced invasion, gross mucin overproduction (72% versus 7%), and their prevalent location (84% of IPNBs in intrahepatic/hilar ducts; 70% of papillary cholangiocarcinomas in extrahepatic ducts). Gastric-type and oncocytic-type tumours were only detected in IPNBs. Expression of mucin core proteins and cytokeratin 20 significantly differed between the two groups. KRAS and GNAS were wild-type genotypes in all but one case of KRAS-mutated IPNB. Patients with IPNB had better recurrence-free survival than those with papillary cholangiocarcinoma (P = 0.007). In multivariate analysis, in which several other prognostic factors (e.g. stromal invasion and lymph node metastasis) were applied, the classification of the two papillary tumours was an independent prognostic factor (P = 0.040). Conclusions Given the significant contrast in clinicopathological features between IPNBs and papillary cholangiocarcinomas, it may be more appropriate to use the diagnostic term ‘IPNB’ for selected tumours that show regular papillary growth, separately from papillary cholangiocarcinomas.

Background Microscopic venous and lymphatic invasion is a known prognostic factor for various cancers, but its prognostic relevance for pancreatic neuroendocrine tumors (PNETs) is unclear. Methods Thirty-two consecutive patients with PNET who had complete resection were included in this study. Venous and lymphatic invasion was identified on elastic tissue or immunohistochemical staining, and correlated with other clinicopathological factors, including recurrence-free survival. Results Venous and lymphatic invasion was identified in nine (28%) and three (9%) patients, respectively. Tumors with venous invasion were of significantly larger size, higher Ki-67 index, and higher mitotic counts. Patients with venous invasion showed significantly worse prognosis than those without venous invasion ( P = 0.001). Five of nine patients (56%) with venous invasion had tumor recurrence, while a relapse was found in one case in patients without venous invasion (n = 23). Lymphatic invasion was not correlated with any other clinicopathological parameters including lymph node metastasis and recurrence-free survival. Predictive factors for recurrence in univariate analysis included microscopic venous invasion, tumor size ≥ 20 mm, non-functionality, and WHO grades. In multivariate analysis where WHO grades and microscopic venous invasion were applied, venous invasion remained a significant predictor of poor recurrence-free survival ( P = 0.021). Conclusions Microscopic venous invasion may serve as a predictive factor for tumor recurrence in patients with resectable PNET. The combination of WHO grades and microscopic venous invasion may assist in the stratification of the patients for risk of tumor recurrence.