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Anatomic liver resection (ALR) has been established to eliminate the tumor-bearing hepatic region with preservation of the remnant liver volume for liver malignancies. Recently, laparoscopic ALR has been widely applied; however, there are few reports on laparoscopic segmentectomy 2. This study aimed to present the standardization of laparoscopic segmentectomy 2 with surgical outcomes.This study included seven patients who underwent pure laparoscopic segmentectomy 2 by the Glissonean approach from January 2020 to December 2021. Four of them had hepatocellular carcinoma, two had colorectal liver metastasis, and one had hepatic angiomyolipoma, which was preoperatively diagnosed with hepatocellular carcinoma. In all patients, preoperative three-dimensional (3D) simulation images from dynamic CT were reconstructed using a 3D workstation. The layer between the hepatic parenchyma and the Glissonean pedicle of segment 2 (G2) was dissected to encircle the root of G2. After clamping or ligation of the G2, 2.5 mg of indocyanine green was injected intravenously to identify the boundaries between segments 2 and 3 with a negative staining method under near-infrared light. Parenchymal transection was performed from the caudal side to the cranial side according to the demarcation on the liver surface, and the left hepatic vein was exposed on the cut surface if possible.The mean operative time for all patients was 281 min. The mean blood loss was 37 mL, and no transfusion was necessary. Estimated liver resection volumes significantly correlated with actual liver resection volumes (r = 0.61, P = 0.035). After the operation, one patient presented with asymptomatic deep venous and pulmonary thrombosis, which was treated with anticoagulant therapy. The mean length of hospital stay was 8.9 days.Laparoscopic segmentectomy 2 by the Glissonean approach is a feasible and safe procedure with the preservation of the nontumor-bearing segment 3 for liver tumors in segment 2.

Pancreatic ductal adenocarcinoma (PDAC) concomitant with intraductal papillary mucinous neoplasm (IPMN) is defined as PDAC occurring apart from IPMN. This study comprehensively investigated the molecular biologic characteristics of PDAC concomitant with IPMN in major genetic alterations, tumor microenvironment, and prognosis by contrast with those of conventional PDAC.The study retrospectively reviewed the data of 158 surgically resected PDAC patients. The driver gene alteration status (KRAS, TP53, CDKN2A, SMAD4, and GNAS) together with the immune and fibrotic status in tumor was evaluated. The prognosis of PDAC concomitant with IPMN and that of conventional PDAC also were compared.No statistically significant difference was found between PDAC concomitant with IPMN and conventional PDAC in the alteration frequency analysis of the major driver genes and the immune and fibrotic status in the tumor microenvironment. Overall survival and disease-free survival between patients who had PDAC concomitant with IPMN and those who had conventional PDAC did not show statistically significant differences in propensity-matched subjects. Furthermore, the co-existence of IPMN was not a poor prognostic factor in the multivariable-adjusted Cox proportional hazards model (hazard ratio, 0.95; 95 % confidence interval, 0.51-1.78).In this study, PDAC concomitant with IPMN had tumor characteristics similar to those of conventional PDAC in terms of the major driver gene alterations, tumor microenvironment, and prognosis.

Portal vein thrombosis (PVT) is a lethal complication of hepatectomy if not properly treated. An 81-year-old woman diagnosed with postoperative PVT after right hepatectomy and caudate lobectomy for perihilar cholangiocarcinoma. Elevation of serum total bilirubin levels, D-dimer levels, and glossy ascites appeared on postoperative day 5 (POD5), and a contrast-enhanced CT confirmed PVT. Thrombi were found from the umbilical portion of the portal vein to the superior mesenteric vein. There were signs of acute liver failure due to thrombi obstructing the portal vein. Therefore, emergent catheter thrombus aspiration was performed under laparotomy. An aspiration catheter was inserted into the superior mesenteric vein from the ileocolic vein. We performed direct aspiration thrombectomy, followed by anticoagulant administration using urokinase via the catheter. Partial recanalization of the portal vein and superior mesenteric vein was observed. To dissolve residual thrombi, edoxaban administration was started on POD6. Contrast-enhanced CT 16 days after her additional operation showed the thrombi had completely disappeared. The patient was discharged on POD76. She had no recurrence of PVT over the next 6 months. Combination therapy of early intervention using aspiration catheter and systemic anticoagulant medication was useful for severe postoperative PVT accompanied with liver failure.

Introduction: Although the relationship between systemic inflammatory responses and prognosis has been known in various cancers, it remains unclear which scores are most valuable for determining the prognosis of extrahepatic cholangiocarcinoma. We aimed to verify the usefulness of various inflammation-based scores as prognostic factors in patients with resected extrahepatic cholangiocarcinoma. Methods: We analyzed consecutive patients undergoing surgical resection for extrahepatic cholangiocarcinoma at our institution between January 2000 and December 2019. The usefulness of the following inflammation-based scores as prognostic factor was investigated: glasgow prognostic score (GPS), modified GPS, neutrophil-to-lymphocyte ratio, platelet to lymphocyte ratio, lymphocyte-to-monocyte ratio, prognostic nutrition index, C-reactive protein to albumin ratio (CAR), controlling nutritional status (CONUT), and prognostic index. Results: A total of 169 patients were enrolled in this study. Of the nine scores, CAR and CONUT indicated prognostic value. Furthermore, multivariate analysis for overall survival revealed that high CAR (>0.23) was an independent prognostic factor (hazard ratio: 1.816, 95% confidence interval: 1.135–2.906, p = 0.0129), along with lymph node metastasis and curability. There was no difference in tumor staging and short-term outcomes between the low CAR (≤0.23) and high CAR groups. Conclusions: CAR was the most valuable prognostic score in patients with resected extrahepatic cholangiocarcinoma.

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 Optimal treatment strategies for advanced hepatocellular carcinoma (HCC) with macroscopic portal vein tumor thrombus (PVTT) remain controversial. Therefore, this study aimed to assess the impact and predictive factors of hepatectomy for HCC with macroscopic PVTT. METHODS This study included 100 patients who presented with intraoperatively confirmed PVTT extending to the first portal branch (Vp3), main portal trunk, or opposite-side portal branch (Vp4) between June 2000 and December 2019. Their postoperative outcomes and predictive factors for survival were evaluated. RESULTS Of the 100 patients, 37 (37%) and 63 (63%) had Vp3 and Vp4 PVTTs, respectively. Moreover, 42 (42%) and 58 (58%) patients underwent R0/1 and R2 hepatectomies, respectively. The median survival time (MST) of all patients with Vp3/4 PVTT was 14.5 months; the 1- and 3-year overall survival rates were 59.6 and 16.8%, respectively. The MSTs of patients with Vp3 and Vp4 PVTTs were 16.1 and 14.3 months, respectively (P = 0.7098). The MSTs of patients who underwent R0/1 and R2 hepatectomies were 14.3 and 14.9 months, respectively (P = 0.3831). All assessed tumor factors (including the Vp status [Vp3 or Vp4], type of resection [R0/1 or R2], intrahepatic maximal tumor size, intrahepatic tumor number, and the existence of extrahepatic metastasis) did not influence the overall survival significantly. CONCLUSIONS Tumor factors, such as the presence of a Vp3/4 PVTT, have a strong impact on survival; however, other multiple tumor factors have a limited impact. Hepatectomy can be an effective treatment option for HCC with Vp3/4 PVTT, and its indications should be considered.

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.

Endoscopic papillectomy for early ampullary tumors is considered a minimally invasive and useful alternative to pancreatoduodenectomy; however, its indications remain unclear. This study aimed to clarify the advantages of endoscopic papillectomy by investigating the clinical outcomes of patients who underwent endoscopic papillectomy or pancreatoduodenectomy for early ampullary tumors. Patients diagnosed with early ampullary tumors (adenoma, Tis, T1a) who underwent endoscopic papillectomy or pancreatoduodenectomy between June 2008 and October 2019 were included, and their clinical outcomes were analyzed. Seventy-four patients (34 patients with adenomas and 40 patients with adenocarcinomas) were divided into two groups, namely endoscopic papillectomy (n = 43) and pancreatoduodenectomy (n = 31). The estimated 5-year overall survival rate of all early ampullary tumors was 92%. Complete resection rate was significantly lower for endoscopic papillectomy patients versus pancreatoduodenectomy patients (48.8% vs. 100%; p

Atezolizumab plus bevacizumab and lenvatinib are the key drugs in the current systemic chemotherapeutic regimen for hepatocellular carcinoma (HCC). Studies have reported the potential effectiveness of lenvatinib introduction after an atezolizumab plus bevacizumab treatment; however, the therapeutic effectiveness of a lenvatinib rechallenge after an atezolizumab plus bevacizumab treatment remains unclear.Thirteen consecutive patients who were rechallenged with lenvatinib after clinical failure following treatments with lenvatinib and atezolizumab plus bevacizumab were included. A comparative study was conducted on the duration and treatment efficacy of the first and second lenvatinib treatments and on the pre- and post-treatment liver function.The median ratios of the 1-month post-treatment alpha-fetoprotein (AFP) levels to the pretreatment AFP levels were 0.750 and 0.667 for the first and second lenvatinib treatments, respectively, without significant difference (p=0.9327). Meanwhile, the median ratios of the 1-month post-treatment albumin-bilirubin (ALBI) scores to the pretreatment ALBI scores were 1.063 and 0.827 for the first and second lenvatinib treatments, respectively, with significant difference (p=0.015). The median duration of the second lenvatinib treatment was significantly shorter than that of the first lenvatinib treatment [2.8 months (range=0.9-4.7 months) vs. 8.7 months (range=3.1-29.7 months)].Lenvatinib re-administration after atezolizumab plus bevacizumab treatment can act as a double-edged sword, as it exerts an anti-tumor effect while being associated with potential liver function deterioration. However, this treatment sequence can be useful, and requires careful monitoring of the transitions in the liver function and the patient's performance status.

Right-sided ligamentum teres (RSLT) is a rare congenital anomaly in which the fetal umbilical vein is connected to the right paramedian trunk of the portal vein. An 80-year-old woman underwent curative sigmoidectomy for sigmoid cancer 3 years prior to presentation. After 1 year, small solitary liver metastasis was noted in segment 4. Because the patient experienced recurrence of the same lesion after chemotherapy and radiofrequency ablation, she was referred to our hospital. CT revealed an anomaly of the liver with RSLT, classified as an independent posterior branch type. The tumor in the left paramedian section was located in the right umbilical portion (RUP), and BDTT was advanced to the common bile duct. Because the estimated future remnant liver volume was 35.2%, transileocecal portal vein embolization (PVE) for the portal branches from the RUP increased it to 43.5% in 3 weeks. Left trisectionectomy with extrahepatic bile duct resection and hepaticojejunostomy were performed. The patient was discharged on postoperative day 75. We successfully performed a left trisectionectomy after PVE in a patient with RSLT. Understanding the vascular and biliary anomalies of patients with RSLT is essential. When the future remnant liver is small, PVE can be considered for safe hepatectomy.

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.

Background Intrahepatic cholangiocarcinoma had been considered a contraindication for liver transplantation because of poorer outcomes. However, incidental intrahepatic cholangiocarcinoma in the explanted liver has been reported because of the difficulty of obtaining an accurate diagnosis in cirrhotic livers on preoperative imaging. Methods We conducted a nationwide survey to analyze the incidence of incidental intrahepatic cholangiocarcinoma and outcomes after liver transplantation, in Japan. Results Forty-five of 64 institutions (70%) responded to our initial investigation. Between January 2001 and December 2015, 6627 liver transplantations were performed in these 45 institutions, with 19 cases (0.3%) of incidental intrahepatic cholangiocarcinoma reported from 12 transplant centers. Six cases were diagnosed as hepatocellular carcinoma preoperatively. The 1-, 3-, and 5-year recurrence-free survival rates were 79%, 45%, and 45%, respectively. Tumor recurrence after liver transplantation was found in 10 patients (53%). The 1-, 3-, and 5-year overall survival rates were 79%, 63%, and 46%, respectively. Conclusions Intrahepatic cholangiocarcinoma at liver transplantation is associated with a high risk of recurrence and poor prognosis, even these tumors are detected incidentally in the explanted liver.

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.

Resecting liver tumors located in Couinaud's segment VII is challenging; the efficacy and safety of laparoscopic liver resection for segment VII lesions compared to open liver resection remain unclear.Medical records of 84 patients who underwent liver resection of segment VII at Kobe University Hospital and Hyogo Cancer Center between 2010 and 2021 were retrospectively analyzed. Surgical outcomes were compared between laparoscopic liver resection and open liver resection groups using propensity matching analysis.Thirty-one and 53 patients underwent laparoscopic liver resection and open liver resection, respectively. After propensity matching, 29 patients were included in each group. The laparoscopic liver resection group had a significantly longer operation time (407 vs. 305 min, P = 0.002), lower blood loss (100 vs. 230 mL, P = 0.004), and higher postoperative alanine aminotransferase levels (436 vs. 252 IU/L, P = 0.008) than the open liver resection group. In patients with liver cirrhosis, the proportion of patients with postoperative liver-specific complications was higher in the laparoscopic liver resection group than in the open liver resection group (57% vs 11%, P = 0.049), although there was no significant difference in postoperative liver-specific complication rates between the groups in patients without liver cirrhosis.For liver resection of segment VII, laparoscopic liver resection led to higher postoperative liver damage than open liver resection. Open liver resection may be better for patients with liver cirrhosis to avoid postoperative liver-specific complications. Laparoscopic liver resection could be an acceptable procedure for patients without liver cirrhosis, with some merits such as less blood loss.

Although many transplant programs have been forced to suspend living donor transplants due to the emergence of coronavirus disease (COVID-19), there are relatively few real-time databases to assess center-level transplant activities. We aimed to delineate the actual impact of COVID-19 on living donor transplant programs and the resumption process in Japan.In a nationwide survey, questionnaires were sent to 32 liver transplant programs that had performed at least more than one case of living donor liver transplantation in 2019 and 132 kidney transplant programs that had performed more than one living donor kidney transplantation in 2018.Thirty-one (96.9%) and 125 (94.7%) liver and kidney transplant programs responded, respectively. In the early pandemic period, 67.7% (21/31) of liver programs and 29.8% (37/125) of kidney programs were able to maintain transplant activities similar to those during the pre-pandemic period. After temporal suspension, 58.1% of kidney programs resumed their transplant activity after the number of local COVID-19 cases peaked. Establishing institutional COVID-19 screening, triage, and therapeutic management protocols was mandatory to resume transplant activity for 64.5% and 67.7% of liver and kidney programs, respectively. In the future wave of COVID-19, 67.7% of liver programs would be affected by institutional COVID-19 intensive care unit-bound patient numbers, and 55.7% of kidney programs would stop if hospital-acquired severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection spreads.THIS NATIONWIDE SURVEY REVEALED FOR THE FIRST TIME HOW LIVING DONOR LIVER AND KIDNEY: transplant programs changed in response to the COVID-19 pandemic in a country where living donor transplantations are predominant.

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.

BACKGROUND The prevalent location and incidence of intraductal papillary neoplasm of the bile duct (IPNB) and invasive carcinoma associated with them have varied markedly among studies due to differences in diagnostic criteria and tumor location. METHODS IPNBs were classified into two types: Type 1 IPNB, being histologically similar to intraductal papillary mucinous neoplasm of the pancreas, and Type 2 IPNB, having a more complex histological architecture with irregular papillary branching or foci of solid-tubular components. Medical data were evaluated. RESULTS Among 694 IPNB patients, 520 and 174 had Type 1 and Type 2, respectively. The levels of AST, ALT, ALP, T. Bil, and CEA were significantly higher in patients with Type 2 than in those with Type 1. Type 1 IPNB was more frequently located in the intrahepatic bile duct than Type 2, whereas Type 2 was more frequently located in the distal bile duct than Type 1 IPNB (P

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.

Undifferentiated pleomorphic sarcoma(UPS)is a non-epithelial malignant tumor with a high rate of recurrence and metastasis. The frequent metastasis site is lung, lymph node, liver and bone. Pancreatic metastasis is rare. 71-year-old woman whose course after right foot UPS resection had been followed up at our hospital. But multiple bone and muscle metastasis occurred 1 year after operation. She had resection or radiation for the recurrence. 3 years after the first operation, PET-CT and EUS-FNA revealed pancreatic tail metastasis. The tumor grew up in 6 months, so we performed laparoscopic distal pancreatectomy. The patient recovered uneventfully and was discharged on post-operative day 14. Currently 5 years and 6 months have passed since the first surgery and she is alive. Function-preserving and minimally invasive surgery for UPS pancreatic metastasis is considered to be essential.

A woman in her 80s was diagnosed with pancreatic tail cancer by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). We performed laparoscopic distal pancreatectomy followed by adjuvant chemotherapy with S-1 for 6 months. One year after surgery, contrast-enhanced computed tomography revealed a 15 mm mass in the posterior wall of the gastric body. EUS showed a hypoechoic mass in the muscular layer in the gastric wall, which was diagnosed as adenocarcinoma by FNA. We diagnosed gastric wall recurrence due to needle tract seeding(NTS)following EUS-FNA and performed partial gastrectomy. Histopathological diagnosis was gastric wall recurrence of pancreatic cancer. Since NTS following EUS-FNA can be proven only by the presence of gastric wall recurrence after surgery for pancreatic body or tail cancer, the actual risk of NTS including peritoneal dissemination is not clear and may have been underestimated. In case of resectable pancreatic body or tail cancer, indication for EUS-FNA should be carefully considered.

A 73-year-old woman underwent a subtotal stomach-preserving pancreaticoduodenectomy, wedge resection of the portal vein, and partial resection of the transverse colon for pancreatic cancer at the age of 71. After 18 months, a computed tomography image showed an 8 mm tumor in the ascending jejunal mesentery. Six months later, the tumor grew to 20 mm and had an increased FDG uptake. The tumor was diagnosed as metastasis of pancreatic cancer to the ascending jejunal mesentery. Since no metastasis was found in the other organs, resection was performed. The pathological results showed adenocarcinoma with proximal lymph node metastasis. The patient was diagnosed with ascending jejunal mesentery metastasis of pancreatic cancer. The patient has remained healthy without recurrent disease 1 year 6 months after the resection. Ascending jejunal mesentery metastasis of pancreatic cancer is a type of distant metastasis. In the absence of metastasis to other organs, it is tolerable and radical resection is possible.

Background Pancreatic resection and radiotherapy are powerful tools in the multidisciplinary local treatment of pancreatic ductal adenocarcinoma (PDAC). However, 10–20% of patients with preoperatively resectable PDAC have radiographically occult metastases, which results in laparotomy without resection. This study aims to explore the utility of intraoperative near-infrared (NIR) imaging with indocyanine green (ICG) during staging laparoscopy to detect PDAC metastasis. Methods This prospective study will evaluate patients with radiographically non-metastatic PDAC before they undergo planned pancreatic resection or chemoradiotherapy. Enrolled patients will receive ICG intravenously (0.5 mg/kg) before the staging laparoscopy. During the staging laparoscopy, the abdominal cavity will be observed using standard white-light laparoscopic imaging and then using NIR-ICG imaging. Suspicious lesions that are detected using standard imaging and/or NIR-ICG imaging will be examined intraoperatively using frozen sections and permanent specimens. We will evaluate the benefit of NIR-ICG imaging based on its ability to identify additional liver or peritoneal lesions that were not detected during standard white-light imaging. Discussion This study will help establish the clinical utility of NIR-ICG imaging to more precisely identify metastases from radiographically non-metastatic PDAC. This approach may help avoid needless major surgery or radiotherapy. Trial registration This protocol was registered on April 1, 2017 on the UMIN Clinical Trials Registry: UMIN000025900 and February 26, 2019 on the Japan Registry of Clinical Trials: jRCT1051180076.

Gadoxetic acid-enhanced magnetic resonance imaging (MRI) is useful in detecting liver metastases from pancreatic ductal adenocarcinoma (PDAC). However, the long examination time limits its utility in the initial workup of patients with PDAC.To evaluate the incremental value of an abbreviated gadoxetic acid-enhanced MRI for the detection of liver metastases in patients with PDAC.Retrospective.Patients (N = 130) with potentially resectable PDAC (women, 58 [44.6%]).1.5 T and 3 T; gradient dual-echo T1-weighted (in-phase and opposed-phase), fat-suppressed fast spin-echo T2-weighted, single-shot echo-planar diffusion-weighted, and three-dimensional fat-suppressed T1-weighted gradient-echo dynamic contrast-enhanced and hepatobiliary phase sequences, as well as contrast-enhanced computed tomography (CECT).Three radiologists independently reviewed three different image sets to detect liver metastases: set 1, CECT alone; set 2, CECT and abbreviated MRI comprising fat-suppressed T2-weighted, diffusion-weighted, and hepatobiliary phase images; and set 3, CECT and standard gadoxetic acid-enhanced MRI.Figure of merit (FOM) was compared using the jackknife alternative free-response receiver operating characteristics, and other per-lesion and per-patient diagnostic parameters for each image set were compared using McNemar's and Fisher's test. P 0.05 was considered statistically significant.A total of 43 liver metastases were identified in 13 patients. Reader-averaged FOM to detect liver metastases were significantly higher for sets 2 (0.884) and 3 (0.886) than for set 1 (0.609), while they were comparable between sets 2 and 3 (P = 0.96). The mean per-patient sensitivities, negative predictive values, and accuracies were significantly higher for sets 2 and 3 than for set 1, while those between sets 2 and 3 were not significantly different (not applicable, P 0.99, and P 0.99, respectively).Gadoxetic acid-enhanced MRI combined with CECT had higher diagnostic performance than CECT alone for the detection of liver metastases in patients with PDAC. The incremental values were comparable for the abbreviated MRI and standard MRI.3 TECHNICAL EFFICACY: Stage 2.

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.

Mutations in IDH1/2 and the epigenetic silencing of TET2 occur in leukaemia or glioma in a mutually exclusive manner. Although intrahepatic cholangiocarcinoma (iCCA) may harbour IDH1/2 mutations, the contribution of TET2 to carcinogenesis remains unknown. In the present study, the expression and promoter methylation of TET2 were investigated in iCCA. The expression of TET2 was assessed in 52 cases of iCCA (small-duct type, n = 33; large-duct type, n = 19) by quantitative PCR, immunohistochemistry (IHC) and a sequencing-based methylation assay, and its relationships with clinicopathological features and alterations in cancer-related genes (e.g., KRAS and IDH1) were investigated. In contrast to non-neoplastic bile ducts, which were negative for TET2 on IHC, 42 cases (81%) of iCCA showed the nuclear overexpression of TET2. Based on IHC scores (area × intensity), these cases were classified as TET2-high (n = 25) and TET2-low (n = 27). The histological type, tumour size, lymph node metastasis and frequency of mutations in cancer-related genes did not significantly differ between the two groups. Overall and recurrence-free survival were significantly worse in patients with TET2-high iCCA than in those with TET2-low iCCA. A multivariate analysis identified the high expression of TET2 as an independent prognostic factor (HR = 2.94; p = 0.007). The degree of methylation at two promoter CpG sites was significantly less in TET2-high iCCA than in TET2-low iCCA or non-cancer tissue. In conclusion, in contrast to other IDH-related neoplasms, TET2 overexpression is common in iCCA of both subtypes, and its high expression, potentially induced by promoter hypomethylation, is an independent poor prognostic factor.

BACKGROUND Approximately 8300 hemophiliacs are registered in Japan, but no comprehensive reports on hepatobiliary and pancreatic surgery (HBPS) have been conducted. This report investigates the current status of HPBS in hemophilia patients in Japan. METHODS The subjects were hemophiliac patients seen between January 1 2007, and December 31 2017, at facilities participating in this study among the facilities for performing high-difficulty cases nationwide designated by the Japanese Society for HBPS. A retrospective examination of short-term outcomes in 49 cases was conducted to assess patient background, disease, surgical procedure, and complications. RESULTS The types of hemophilia were A: 43 cases, B: four cases, and von Willebrand disease: two cases (hemophilia severity: mild 32, moderate seven, severe 10). The target malignant diseases for surgery were hepatocellular carcinoma (HCC) in 20 cases, intrahepatic cholangiocellular carcinoma (CCC) in four cases, combined HCC-CCC in two cases, hilar CCC in two cases, and pancreatic cancer in four cases. As for the surgical procedure, limited resection (subsegmentectomy and partial hepatectomy) was performed in 16 cases of HCC even with normal liver function tests. Pancreaticoduodenectomy and distal pacreatectomy were performed for pancreatic cancers as in the standard procedure. Postoperative complications were postoperative bleeding in two cases after hepatectomy and one after pancreatectomy in one case. When compared with Japanese National Clinical Data base, the complication rates after hepatectomy and pancreatectomy were not conspicuous in hemophilic patients. CONCLUSIONS As long as they are performed in qualified centers, complication rate is not increased in hemophilic patients undergoing HBPS.

Background Radical antegrade modular pancreatosplenectomy (RAMPS) is an isolation procedure in pancreatosplenectomy for pancreatic body/tail cancer. Connective tissues around the bifurcation of the celiac axis are dissected, followed by median-to-left retroperitoneal dissection. This procedure has the potential to isolate blood and lymphatic flow to the area of the pancreatic body/tail and the spleen to be excised. This is achieved by division of the inflow artery, transection of the pancreas, and then division of the outflow vein in the early phases of surgery. In cases of pancreatic ductal adenocarcinoma (PDAC), the procedure has been shown to decrease intraoperative blood loss and increase R0 resection rate by complete clearance of the lymph nodes. This trial investigates whether the isolation procedure can prolong the survival of patients with pancreatic ductal adenocarcinoma who undergo distal pancreatosplenectomy (DPS) compared with those that undergo the conventional approach. Methods/design Patients with PDAC scheduled to undergo DPS are randomized before surgery to undergo either a conventional procedure (arm A) or to undergo the isolation procedure (arm B). In arm A, the pancreatic body, tail, and spleen are mobilized, followed by removal of the regional lymph nodes. The splenic vein is transected at the end of the procedure. The timing of division of the splenic artery (SA) is not restricted. In arm B, regional lymph nodes are dissected, then we transect the root of the SA, the pancreas, then the splenic vein. At the end of the procedure, the pancreatic body/tail and spleen are mobilized and removed. In total, 100 patients from multiple Japanese high-volume centers will be randomized. The primary endpoint is 2-year recurrence-free survival by intention-to-treat analysis. Secondary endpoints include intraoperative blood loss, R0 resection rate, and overall survival. Discussion If this trial shows that the isolation procedures can improve survival with a similar R0 rate and with a similar number of lymph node dissections to the conventional procedure, the isolation procedure is expected to become a standard procedure during DPS for PDAC. Conversely, if there were no significant differences in endpoints between the groups, it would demonstrate justification of either procedure from surgical and oncological points of view. Trial registration UMIN Clinical Trials Registry UMIN000041381. Registered on 10 August 2020. ClinicalTrials.gov NCT04600063. Registered on 22 October 2020.

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

Introduction: Although the primary treatment option for hilar cholangiocarcinoma (HC) has been surgical resection, most patients present with unresectable advanced tumors at the time of diagnosis. Particle therapy (PT) holds great potential for HC, even though the anatomical proximity to the gastrointestinal tract prevents delivering a radical dose to the tumor. Space-making PT (SMPT), consisting of spacer placement surgery and subsequent PT, has been developed to minimize complications and maximize the therapeutic benefit of dose escalation for HC. This study aimed to conduct a dosimetric evaluation and examine the effectiveness of SMPT for the treatment of HC. Methods: Between 2007 and 2018, 12 patients with unresectable HC treated with SMPT were enrolled. The treatment outcomes and effectiveness of spacer placement surgery were evaluated through analyses of pre- and post-surgical parameters of dose-volume histograms. Results: All patients completed the planned SMPT protocol. The median survival time was 29.6 months, and the 1- and 3-year overall survival rates were 82.5% and 45.8%, respectively. The mean V95% value (volume irradiated with 95% of the planned treatment dose) of the gross tumor volume and clinical target volume after spacer placement surgery improved to 98.5% and 96.6% from preoperative values of 85.6% and 78.1%, respectively (p = 0.0196 and p = 0.0053, respectively). Grade 3 or higher adverse events after SMPT were seen in 6 patients. Discussion/Conclusion: SMPT led to improvements in dosimetric parameters and showed good feasibility and excellent outcomes. SMPT can be a promising novel alternative for unresectable HC.

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.

Resected bile duct cancers often relapse during postoperative follow-up. The aim of this study was to detect predictors of early recurrence in patients with extrahepatic bile duct cancer.Consecutive cases (n = 162) of extrahepatic bile duct cancer in which R0 or R1 resection was achieved in Kobe University Hospital between 2000 and 2016 were divided into three groups [early recurrence (ER), within 6 months of surgery, late recurrence (LR), and no recurrence (NR)] and their clinicopathological features were compared.Twenty-two patients (14%) developed ER and 69 (43%) developed LR after surgery. The rates of lymph node metastasis and residual cancer status were similar in all three groups. Liver metastasis was more common in the ER group than in the LR group (59% vs. 32%, p = 0.02). ER had a significantly worse prognosis than LR and NR (7% vs. 44% vs. 85% at 1 year, p 0.01, respectively). Multivariate analysis showed that age 75 years, serum CA19-9 1008 U/ml and perineural invasion were independent predictors of early recurrence.High serum CA19-9 values ( 1008 U/ml) were an independent predictor of early recurrence. Neoadjuvant therapy and aggressive adjuvant therapy may be beneficial for patients who show highly elevated CA19-9 values before surgery.

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

ADP-ribosylation factor-like 4c (ARL4C) is identified as a small GTP-binding protein, which is expressed by Wnt and EGF signaling and plays an important role in tubulogenesis of cultured cells and the ureters. ARL4C is little expressed in adult tissues, but it is highly expressed in lung cancer and colorectal cancer and shown to represent a molecular target for cancer therapy based on siRNA experiments. This study revealed that ARL4C is highly expressed in primary hepatocellular carcinoma (HCC) tumors and colorectal cancer liver metastases, and that ARL4C expression is associated with poor prognosis for these cancers. Chemically modified antisense oligonucleotides (ASO) against ARL4C effectively reduced ARL4C expression in both HCC and colorectal cancer cells and inhibited proliferation and migration of these cancer cells in vitro. ARL4C ASOs decreased the PIK3CD mRNA levels and inhibited the activity of AKT in HCC cells, suggesting that the downstream signaling of ARL4C in HCC cells is different from that in lung and colon cancer cells. In addition, subcutaneous injection of ARL4C ASO was effective in reducing the growth of primary HCC and metastatic colorectal cancer in the liver of immunodeficient mice. ARL4C ASO accumulated in cancer cells more efficiently than the surrounding normal cells in the liver and decreased ARL4C expression in the tumor. These results suggest that ARL4C ASO represents a novel targeted nucleic acid medicine for the treatment of primary and metastatic liver cancers.

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.

Objectives Small proline-rich protein 1A (SPRR1A) is recognized as a squamous differentiation marker but is also upregulated in some non-squamous cancers. However, its expression in pancreatic ductal adenocarcinoma (PDAC) has not been investigated. This study elucidated the expression of SPRR1A in PDAC and its effect on the prognosis and malignant behavior of PDAC. Methods We examined the SPRR1A expression by immunohistochemistry in 86 surgical PDAC cases and revealed the relationship between its expression and the prognosis of the PDAC patients. Furthermore, we overexpressed SPRR1A in pancreatic cancer cell lines (PK-1 and Panc-1) and assessed the phenotype and gene expression changes in vitro. Results Among the 84 cases, excluding 2 with squamous differentiation, 31 (36.9%) had a high SPRR1A expression. The overall survival (median 22.1 months vs. 33.6 months, p = 0.0357) and recurrence-free survival (median 10.7 months vs. 15.5 months, p = 0.0298) were significantly lower in the high-SPRR1A-expression group than in the low-SPRR1A-expression group. A multivariate analysis indicated that a high SPRR1A expression (HR 1.706, 95% CI 1.018 to 2.862, p = 0.0427) and residual tumor status (HR 2.687, 95% CI 1.487 to 4.855, p = 0.00106) were independent prognostic factors. The analysis of TCGA transcriptome data demonstrated that the high-SPRR1A-expression group had a significantly worse prognosis than the low-SPRR1A-expression group, which supported our data. SPRR1A overexpression in PK-1 and Panc-1 did not result in remarkable changes to in vitro phenotypes, such as the cell proliferation, chemo-resistance, EMT, migration or global gene expression. Conclusion Increased expression of SPRR1A is associated with a poor prognosis in PDAC and may serve as a novel prognostic marker. However, our in vitro study suggests that the SPRR1A expression may be a consequence, not a cause, of the aggressive behavior of PDAC.

BACKGROUND Although liver transplantation is widely accepted as the therapeutic strategy for end-stage liver failure, complication of hepatic venous outflow obstruction remains lethal. Currently, ensuring a single wide orifice in both the graft and recipient inferior vena cava has been proposed to avoid hepatic venous outflow obstruction with no theoretical concept. METHODS We herein report a standardization technique for the reconstruction of the hepatic vein based on the causal analysis. RESULTS During the put-in process, the graft must be positioned in contact with the recipient diaphragm and slightly pushed to the cranial direction to simulate the state after abdominal closure. Because there is no extra space between the graft and diaphragm, the graft could not rotate about the anastomotic site of the inferior vena cava toward the diaphragm after abdominal closure as the intestinal pressure increases, and accordingly hepatic venous outflow obstruction does not develop. CONCLUSIONS With this concept, all transplant surgeons can successfully and easily perform hepatic vein reconstruction without total clamping of the inferior vena cava and without outflow block.

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.