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Immune checkpoint inhibitors (ICIs) could cause type 1 diabetes (T1D). However, the underlying mechanism remains unclear. We immunohistochemically analyzed pancreatic specimens from three individuals with ICI-related T1D, and their histopathological data were compared those from three patients who had received ICI therapy but did not develop T1D (non-T1D) and seven normal glucose-tolerant subjects as control subjects. All ICI-related T1D patients had susceptible HLA haplotypes. In ICI-related T1D, the β-cell area decreased and the α-cell area increased compared with non-T1D and control subjects. The number of CD3-positive cells around islets increased in ICI-related T1D and non-T1D compared with control subjects, while the number of CD68-positive cells around islets increased in ICI-related T1D compared with non-T1D and control subjects. The expression ratios of programmed death-ligand 1 (PD-L1) on islets decreased in non-T1D and almost completely disappeared in ICI-related T1D, while PD-L1 expression was observed in most cells of pancreatic islets in control subjects. This study, therefore, indicates that ICI therapy itself could reduce PD-L1 expression on islets in all subjects, which may be related to β-cell vulnerability. In addition, we showed that absence of PD-L1 expression on β-cells, genetic susceptibility, and infiltration of macrophages as well as T lymphocytes around islets might be responsible for T1D onset.ARTICLE HIGHLIGHTS

Purpose Postoperative pancreatic fistula is a serious complication of distal pancreatectomy. Although many studies have described the incidence and risk factors associated with postoperative pancreatic fistula (POPF), few have focused on the healing time. This study investigated the healing time and potential factors associated with the healing time of POPF after distal pancreatectomy (DP). Methods Among 114 patients that underwent DP in our hospital from January 2010 to December 2020, we included 88 that developed POPF. The healing time for a postoperative pancreatic fistula was defined as the interval between the completion of DP and the removal of all drains related to the treatment for POPF. Based on the definition, three cases who required additional treatment after removal of all drains were excluded from this study. Clinical factors associated with the fistula healing times were investigated in the 85 patients. Results The average POPF healing time was 11 ± 10 days (median: 6 days, range: 3‐57). We found that the neutrophil‐to‐lymphocyte ratio, a marker of inflammatory and nutritional status, was the only factor independently associated with the POPF healing time; the mean healing time was significantly shorter in patients with neutrophil‐to‐lymphocyte ratio ≤2.1 (8 ± 6 days) than in those with neutrophil‐to‐lymphocyte ratio >2.1 (13 ± 12 days; P = .0139). Conclusion We demonstrated that the neutrophil‐to‐lymphocyte ratio could independently predict the POPF healing time after DP. These findings suggested that improving the neutrophil‐to‐lymphocyte ratio might shorten the healing times for POPF after DP., The healing time of postoperative pancreatic fistula after distal pancreatectomy was associated significantly with the neutrophil‐to‐lymphocyte ratio. This result suggested that improving patients' inflammatory and nutritional status might shorten that healing time.

Purpose: In biliary tract cancer (BTC), malignancy is strongest at the invasion front. To improve the BTC prognosis, the invasion front should be controlled. We evaluated tumor-stroma crosstalk at the tumor center and at the invasion front of BTC lesions. We investigated the expression of SPARC, a marker of cancer-associated fibroblasts, and determined its ability to predict BTC prognosis after neoadjuvant chemoradiotherapy (NAC-RT). Methods: We performed immunohistochemistry to evaluate SPARC expression in resected specimens from patients that underwent BTC surgery. We established highly invasive (HI) clones in two BTC cell lines (NOZ, CCLP1), and performed mRNA microarrays to compare gene expression in parental and HI cells. Results: Among 92 specimens, stromal SPARC expression was higher at the invasion front than at the lesion center (p=0.014). Among 50 specimens from patients treated with surgery alone, high stromal SPARC expression at the invasion front was associated with a poor prognosis (recurrence-free survival: p=0.033; overall survival: p=0.017). Coculturing fibroblasts with NOZ-HI cells upregulated fibroblast SPARC expression. mRNA microarrays showed that connective tissue growth factor (CTGF) was upregulated in NOZ-HI and CCLP1-HI cells. A CTGF knockdown suppressed cell invasion in NOZ-HI cells. Exogeneous CTGF upregulated SPARC expression in fibroblasts. SPARC expression at the invasion front was significantly lower after NAC-RT, compared to surgery alone (p=0.003). Conclusion: CTGF was associated with tumor-stroma crosstalk in BTC. CTGF activated stromal SPARC expression, which promoted tumor progression, particularly at the invasion front. SPARC expression at the invasion front after NAC-RT may serve as a prognosis predictor.

Purpose Decreasing intraoperative blood loss is one reported advantage of laparoscopic surgery compared with open surgery. However, several reports indicate that blood loss during laparoscopic surgery may be underestimated. No studies have evaluated this possibility in laparoscopic distal pancreatectomy (LDP). Here we evaluated estimated blood loss (e-BL) compared to actual intraoperative blood loss (i-BL) during distal pancreatectomy (DP). Methods This study included 114 patients undergoing DP in our institution during the study period. We examined the relationship between i-BL and e-BL. Based on these results, we further investigated the relationship with LDP. Results The laparoscopic approach was used in a significantly higher percentage of patients in e-BL > i-BL group compared to e-BL p p p = 0.0017). The e-BL > i-BL trend in LDP group was consistent regardless of the indication for DP. In contrast, the finding of i-BL > e-BL in ODP group was limited to patients with pancreatic cancer. Conclusion During LDP, e-BL was significantly more than i-BL. During ODP, e-BL was significantly less than i-BL, only in patients with pancreatic cancer. These results suggested the possibility of i-BL underestimation during LDP, and overestimation during ODP in cases with pancreatic cancer.

The prognosis of congenital heart disease in children has improved, but late complications in adulthood are becoming an important problem. One late complication after congenital heart surgery is congestive liver disease, leading to liver cirrhosis and hepatocellular carcinoma (HCC). The Rastelli procedure is one of the surgical methods for transposition of the great arteries. We present the first case of HCC derived from Rastelli procedure-related congestive liver disease in a 41-year-old male. The patient underwent the Rastelli operation at 2 years of age and right ventricular outflow tract reconstruction at 10 and 35 years of age due to right ventricular outflow tract obstruction. At 41 years of age, a hepatic tumor was detected by computed tomography. Abdominal enhancing computed tomography revealed a partially hypervascular tumor in segment 2 in early phase and wash-out in late phase. The patient was diagnosed with HCC and underwent left lateral segmentectomy of the liver, splenectomy, and partial gastrectomy. The patient was discharged on the 28th postoperative day without postoperative complications. In the management of patients after the Rastelli operation, surveillance for congestive liver disease and HCC development is important, even if the patients have undergone right ventricular outflow tract reconstruction.

Perihilar cholangiocarcinoma (PCC) is a complex disorder involving the hepatic hilum. Multiple endoscopic retrograde cholangiopancreatography sessions are necessary for diagnosis and treatment with underlying cholangitis risk. Our aim is to clarify the initial-drainage-related prognostic factors of PCC.This study was a single-center retrospective study. A total of 104 consecutive patients diagnosed with PCC from January 2010 to February 2020 were enrolled. We defined the diagnostic period as the time between the first biliary drainage attempt and the final drainage when treatment, including surgery or chemotherapy, was started. We focused on this initial period and analyzed the endoscopy-related factors that affected mortality.Overall survival of all PCC patients was 599 days. Overall survival of surgically treated patients and unresectable patients were 893 days and 512 days, respectively. In 48 surgically treated patients, drainage-related cholangitis within the diagnostic period, defined as new cholangitis that occurred after the first biliary drainage attempt, worsened overall survival from 1460 days to 607 days. Endoscopic sphincterotomy, the first drainage method other than endoscopic nasobiliary drainage, and four or more endoscopic retrograde cholangiopancreatography sessions were risk factors for drainage-related cholangitis. Drainage-related cholangitis increased pathological lymph node metastasis. Percutaneous transhepatic biliary drainage as final drainage was the only prognostic factor in unresectable chemotherapy-treated patients.Drainage-related cholangitis worsened the prognosis in PCC patients who underwent surgery. Appropriate endoscopic retrograde cholangiopancreatography strategies, especially during the diagnostic period, are of great importance in PCC.

Hepatocellular carcinoma (HCC) is the second leading cause of cancer‐related death. High recurrence rates after curative resection and the lack of specific biomarkers for intrahepatic metastases are major clinical problems. Recently, exosomal microRNAs (miRNAs) have been reported to have a role in the formation of the pre‐metastatic niche and as promising biomarkers in patients with malignancy. Here we aimed to clarify the molecular mechanisms of intrahepatic metastasis and to identify a novel biomarker miRNA in patients with HCC. A highly intrahepatic metastatic cell line (HuH‐7M) was established by in vivo selection. HuH‐7M showed increased proliferative ability and suppression of apoptosis and anoikis. HuH‐7M and the parental cell (HuH‐7P) showed the similar expression of epithelial‐mesenchymal transition markers and cancer stem cell markers. In vivo, mice treated with exosomes derived from HuH‐7M showed increased tumorigenesis of liver metastases. Exosomes from HuH‐7M downregulated endothelial cell expression of vascular endothelial‐cadherin (VE‐cadherin) and zonula occludens‐1 (ZO‐1) in non‐cancerous regions of liver and increased the permeability of FITC‐dextran through the monolayer of endothelial cells. The miRNAs (miR‐638, miR‐663a, miR‐3648, and miR‐4258) could attenuate endothelial junction integrity by inhibiting VE‐cadherin and ZO‐1 expression. In patients with HCC, higher serum exosomal miR‐638 expression was associated with tumor recurrence. In conclusion, the miRNAs secreted from a highly metastatic cancer cell can promote vascular permeability via downregulation of endothelial expression of VE‐cadherin and ZO‐1. Serum exosomal miR‐638 expression holds potential for serving as a significant and independent prognostic marker in HCC., miR‐638, miR‐663a, miR‐3648, and miR‐4258 downregulate VE‐cadherin and ZO‐1 expression in HUVECs.

In Japan, 437 pancreas transplantations (PTx) were carried out between 2000 and 2019. Clinical data for all PTx cases are registered in the Japan Pancreas Transplant Registry of the Japan Society for Pancreas and Islet Transplantation. Here we analyzed the registry data to describe the current status of PTx in Japan. The 437 PTx included 410 from deceased donors (407 from brain‐dead and 3 from non‐heart‐beating donors) and 27 from living donors. We investigated the clinical characteristics of the 410 PTx from deceased donors. The rate of marginal donors using expanded donor criteria was higher in Japan than in other countries. At 1/5/10 years post‐PTx, the overall survival rates were 95.8%/94.2%/88.7%, and the graft survival rates were 85.9%/76.2%/67.4% for pancreas and 93.2%/90.8%/78.2% for kidney (non‐censored for death). These rates were comparable to those in other countries. When stratified by PTx category, survival was significantly better following simultaneous pancreas‐kidney transplantation (SPK) compared to pancreas‐after‐kidney transplantation (PAK) or PTx alone (PTA). Immunological rejection was more frequently the cause of graft loss in PAK/PTA cases than in SPK cases, potentially contributing to the poorer survival in PAK/PTA. These outcomes highlight two main concerns: substantial incidence of pancreas graft loss, and inferior outcomes after PAK/PTA. Overall, PTx outcome is favorable in Japan, despite the high rate of marginal donors. To improve outcomes, it is important to prevent and manage each cause of pancreas graft loss. Overcoming the poorer survival in PAK/PTA may require new immunosuppressive protocols or allogenic islet transplantation., In this article, we summarized the current state of pancreas transplantation (PTx) in Japan based on data from the nationwide registry. Our results showed favorable posttransplant outcomes comparable to those of other countries, despite a high rate of marginal donors with expanded donor criteria.

Objectives In the 9th edition of the Japanese Classification of Colorectal, Appendiceal, and Anal Carcinoma (JCCRC), ovarian metastasis is classified as distant metastasis. We assessed the significance of resection of ovarian metastases and the validity of this 9th edition of JCCRC for ovarian metastases from colorectal cancer (CRC). Methods We retrospectively analyzed the clinicopathological factors and overall survival of 17 patients with ovarian metastases from CRC who underwent resection and 110 female CRC patients with Stage IV (M1a) disease. Results The patients with only ovarian metastases who underwent resection had a longer median survival time than patients with both ovarian and peritoneal metastases who underwent resection (45.4 months vs. 9.3 months, P = 0.029). The 5-year overall survival of the patients with only ovarian metastases who underwent R0 resection was as long as that of the female Stage IV (M1a) CRC patients after R0 resection (50% vs. 48%, P = 0.334). Conclusions We found that, after resection, patients with only ovarian metastases had significantly better prognoses than patients with ovarian and peritoneal metastases. R0 resection of ovarian metastasis indicated as good prognosis as R0 resection of metastasis to one distant organ without ovaries. So the 9th edition of JCCRC, which classifies ovarian metastasis from CRC as distant metastasis, is appropriate.

Background An accurate evaluation of neoadjuvant treatment is important to maximize the prognostic benefit of this strategy in each individual patient. The main aim of the present study is to investigate the difference between carbohydrate antigen 19‐9 and fluorine‐18 fluorodeoxyglucose positron emission tomography (FDG‐PET) in evaluating the response to neoadjuvant treatment for resectable and borderline resectable pancreatic ductal adenocarcinoma (PDAC) patients. Methods Pancreatic ductal adenocarcinoma patients with positive standard uptake values (SUV) on FDG‐PET before neoadjuvant chemoradiotherapy (NACRT) were enrolled (n = 141). In all patients, CA19‐9 and FDG‐PET were evaluated before the initiation of and after the completion of NACRT. The statuses of CA19‐9 and FDG uptake alterations during NACRT were assessed in association with survival and tumor recurrence profiles. Results A favorable response in each CA19‐9 and FDG‐PET was significantly related to better survival, respectively, than the unfavorable response (44.3% vs 19.5%, P, CA19‐9 and PET evaluation provided oncologically different risk assessments in terms of tumor recurrence profile in NACRT for resectable and borderline resectable PDAC. The status on CA19‐9 and PET was associated with different profiles of tumor recurrence. Only patients with a favorable response in terms of both CA19‐9 (normalization) and PET status (>50% decrease in SUV‐max) after NACRT gained the optimal prognostic benefit.

The use of a plastic stent (PS) in resectable patients with distal malignant biliary obstruction (DMBO) is uncommon due to the high failure rate of this method. This study evaluated the efficacy and safety of a double-layer, large-diameter PS as a bridge to surgery compared with a conventional PS. This was a single-center retrospective cohort study. In total, 129 consecutive patients with DMBO underwent pancreaticoduodenectomy between January 2011 and March 2018. Fifty-five patients who preoperatively underwent plastic biliary drainage were enrolled. The patients were divided into two groups based on stent diameter: a large-diameter plastic stent (LPS) group and a small-diameter plastic stent (SPS) group. The primary endpoint was the stent patency period, and the secondary endpoint was the medical cost. Thirty-six patients received SPSs; 19 patients received LPSs. The patency rate until surgery was significantly higher in the LPS group than in the SPS group (89.5% vs. 41.7%, P = 0.0006). Multivariate analysis revealed that LPS use was significantly associated with sufficient stent patency. The total cost of LPS use was significantly lower than that of SPS use. LPSs had longer patency and reduced medical costs than SPSs. LPSs may be suitable for patients with DMBO who are scheduled to undergo surgery.

CXCL9, an IFN‐γ inducible chemokine, has been reported to play versatile roles in tumor‐host interrelationships. However, little is known about its role in intrahepatic cholangiocarcinoma (iCCA). Here, we aimed to elucidate the prognostic and biological implications of CXCL9 in iCCA. Endogenous CXCL9 expression and the number of tumor‐infiltrating lymphocytes were immunohistochemically assessed in resection specimens. These data were validated in mice treated by silencing CXCL9 with short hairpin RNA. In addition, the induction of endogenous CXCL9 and the effects of CXCL9 on tumor biological behaviors were evaluated in human cholangiocarcinoma cell lines. Immunohistochemical analyses revealed that high CXCL9 expression was closely correlated with prolonged postoperative survival and a large number of tumor‐infiltrating natural killer (NK) cells. In fact, due to the trafficking of total and tumor necrosis factor‐related apoptosis‐inducing ligand‐expressing NK cells into tumors, CXCL9‐sufficient cells were less tumorigenic in the liver than CXCL9‐deficient cells in mice. Although CXCL9 involvement in tumor growth and invasion abilities differed across cell lines, it did not exacerbate these abilities in CXCL9‐expressing cell lines. We showed that CXCL9 was useful as a prognostic marker. Our findings also suggested that CXCL9 upregulation might offer a therapeutic strategy for treating CXCL9‐expressing iCCA by augmenting anti–tumor immune surveillance., CXCL9, an IFN‐γ inducible chemokine, plays versatile roles in the tumor‐host interrelationship. In this study, we demonstrated that elevated intratumoral CXCL9 expression was associated with a large number of tumor‐infiltrating NK cells, leading to favorable postoperative survival in patients with intrahepatic cholangiocarcinoma. Upregulation of CXCL9 might be an immunotherapeutic approach for treating intrahepatic cholangiocarcinoma.

Immunomodulatory drugs such as lenalidomide (LEN) have shown significant anti-tumor activity against hematologic malignancies and they may have similar actions on solid tumors as well. We studied the effect of a new analog of the immunomodulatory drugs (CC-122) on the growth of hepatocellular carcinoma (HCC) and explored mechanisms of anti-tumor activity by analyzing expression of a novel oncogenic T-cell factor (TCF)-4 J and its downstream gene activation. LEN and CC-122 significantly reduced the expression levels of TCF-4 J and its target genes (SPP1, AXIN2, MMP7, ASPH, CD24, ANXA1, and CAMK2N1); however, CC-122 was more potent. In a xenograft tumor model with a HAK-1A-TCF-4 J derived stable cells, tumor growth was significantly inhibited by CC-122, but not by LEN or vehicle control. The mice with HCC xenograft tumors treated with CC-122 exhibited decreased TCF-4 J expression compared to LEN and control. Furthermore, expression of TCF-4 J-responsive target genes (SPP1, AXIN2, MMP7, ASPH, JAG1, CD24, ANXA1, and CAMK2N1) was reduced by CC-122 and not by LEN or control. These results suggest that CC-122 inhibits HCC tumor growth through downregulation of the oncogenic TCF-4 J isoform.

[Background] The prognosis of congenital heart disease in children has improved, but late complications in adulthood are becoming an important problem. One late complication after congenital heart surgery is congestive liver disease, leading to liver cirrhosis and hepatocellular carcinoma (HCC). The Rastelli procedure is one of the surgical methods for transposition of the great arteries, and patients are thought have a low post-surgical risk of congestive hepatopathy by receiving re-intervention for right ventricular outflow tract obstruction.[Case presentation] We present the first case of HCC derived from Rastelli procedure-related congestive liver disease in a 41-year-old male. The patient underwent the Rastelli operation at 2 years of age and right ventricular outflow tract reconstruction at 10 and 35 years of age due to right ventricular outflow tract obstruction. At 41 years of age, a hepatic tumor was detected by computed tomography. Abdominal enhancing computed tomography revealed a partially hypervascular tumor in segment 2 in early phase and wash-out in late phase. The patient was diagnosed with HCC and underwent left lateral segmentectomy of the liver, splenectomy, and partial gastrectomy. The patient was discharged on the 28th postoperative day without postoperative complications. The resected tumor pathologically revealed moderately differentiated HCC and F3 liver fibrosis.[Conclusions] In the management of patients after the Rastelli operation, surveillance for congestive liver disease and HCC development is important, even if the patients have undergone right ventricular outflow tract reconstruction.

In Japan, the first pancreas transplantation was performed in 1984 from a brain-dead donor; subsequently, however, the concept of brain death became a social issue. Thereafter, the "Organ Transplant Act", which enables brain-dead transplantation, was enacted in 1997, and then revised in 2010 so that donation after brain death became possible only with the consent of the family. Under the recipient selection and registration system developed after the enactment of the "Organ Transplant Act", more than 400 pancreas transplants have been carried out at facilities certified for brain-dead pancreas transplantation in Japan. Of the 410 total cadaveric pancreas transplants performed by the end of 2019, the patient survival and pancreatic and kidney graft survival rates were considered to be comparable to those in the United States and Europe despite the high frequency of marginal donors. Minimally invasive allogenic islet transplantation came to be covered by national health insurance in 2020 following good outcomes of a recent trial. Furthermore, to overcome the serious donor shortage in Japan, development of xenogeneic islet transplantation and regenerative medicine using stem cells is in progress, with xenotransplantation using porcine islets appearing particularly promising.

Background The Fontan procedure has become the standard operation for patients with single ventricle physiology. Due to cardiac hypokinesis and high central venous pressure, laparoscopic approach, especially in hepatectomy, was considered as controversial after the Fontan procedure. We presented a case of hepatocellular carcinoma (HCC) that was successfully treated by pure laparoscopic hepatectomy with stable pneumoperitoneum after the Fontan procedure. Case presentation An 18-year-old man was referred to our hospital for examination of a hepatic tumor. The patient underwent the Fontan procedure for single ventricle physiology at 6 years of age. Abdominal contrast-enhanced computed tomography (CT) revealed a hypovascular mass in segment 2 and a hypervascular mass in segment 4 of the arterial phase, followed by a delayed washout. CT arteriography revealed that both masses showed hypervascular tumors, and CT during arterial portography showed that both were low-density masses. The patient’s general condition was good, and cardiac and respiratory functions were well maintained. Pure laparoscopic hepatectomy was safely performed by keeping the pneumoteritoneum pressure under 6–8 mmHg and monitoring central venous pressure (11–21 mmHg) and end-tidal carbon dioxide. The Pringle maneuver was applied during hepatic resection. The non-anatomical resections were completed without intraoperative complications. The patient was discharged on the 9th postoperative day without postoperative complications. Conclusions Our report suggests that treatment of HCC by pure laparoscopic hepatectomy after Fontan circulation can be safely performed in patients under sufficient circulatory management.

In cases where liver tumors invade the inferior vena cava (IVC), IVC resection along with liver resection may be needed to effect a cure. Furthermore, if the IVC defect is large, IVC reconstruction with vascular graft after resection is required. There are limited reports of cases of IVC reconstruction using a graft. By reviewing data from the literature of previous studies, the present study was aimed at investigating the surgical outcomes of liver resection with IVC resection and reconstruction using an artificial vascular graft. PubMed was searched for previous articles reporting cases with the combined surgery. The search was limited to articles in English, and cases with exceptional surgeries such as in situ cold perfusion, and ante situm and ex vivo techniques were excluded from this study. Surgical outcomes of the extracted cases were investigated. Cases dealt only with primary closure after IVC resection, and those in which the IVC tumor thrombus was treated by opening the IVC wall, removing the thrombus and then closing the IVC without wall excision were not included in this study. The literature search identified 13 studies, including 111 cases. Operative mortality in the reported cases was 8.1% (9 out of 111 cases). Thrombus in the artificial vascular graft was observed in two cases, and patency of the graft during the follow‐up period was confirmed in 109 of the 111 cases (98.2%). These results suggested that the surgical outcomes of liver resection combined with IVC resection and reconstruction using the artificial vascular graft were favorable.

Patient: Male, 90 Final Diagnosis: Ruptured cystic artery pseudoaneurysm Symptoms: Epigastric pain • Fever Medication: — Clinical Procedure: Open cholecystectomy Specialty: Gastroenterology and Hepatology Objective: Rare disease Background: Cystic artery pseudoaneurysm is rare, and some cases are associated with inflammation of the gallbladder. There is limited information regarding this condition, and the clinical features remain unclear. This report is a case of ruptured cystic artery pseudoaneurysm diagnosed by computed tomography (CT) imaging and treated with urgent cholecystectomy and is supported by a literature review of previous cases. Case Report: A 90-year-old man, who had developed acute cholecystitis due to a gallstone one month previously, was referred to our hospital. He developed fever and epigastric pain while waiting for a scheduled elective cholecystectomy. Laboratory investigations showed elevated markers of inflammation and elevated hepatobiliary enzyme levels. Computed tomography (CT) imaging showed cholecystitis and pseudoaneurysm of the cystic artery. The pseudo-aneurysm had ruptured and was accompanied by the formation of a hematoma within the gallbladder that involved the liver bed. Having made the preoperative diagnosis, an urgent open laparotomy was performed, during which the gallbladder was found to have perforated. The hematoma penetrated into the liver bed. Cholecystectomy was performed, and the pseudoaneurysm of the cystic artery was extirpated. There were no serious postoperative complications. A literature review identified 50 previously reported case of cystic artery pseudoaneurysm. Conclusions: A case of ruptured cystic artery pseudoaneurysm, successfully treated with urgent cholecystectomy is reported, supported by a literature review of previous cases and characterization of the clinical features of this rare condition.

Clinically-relevant postoperative pancreatic fistula (CR-POPF) is one of the most serious complications following pancreaticoduodenectomy. While many investigators have studied risk factors for the development of CR-POPF, few studies have focused on time needed for CR-POPF healing in patients who develop this complication. The present study enrolled 38 cases in whom CR-POPF developed following pancreaticoduodenectomy (24.1%) out of 158 cases receiving treatment with pancreaticoduodenectomy between 2009 and 2017 for periampullary diseases. CR-POPF healing time, was defined as the length of time from the day of pancreaticoduodenectomy to the day when intraabdominal drainage tubes used for CR-POPF treatment were removed, were assessed and factors affecting the healing time were investigated. The mean CR-POPF healing time was 40.2±21.7 days (median; 35 days, range; 10-110 days). Univariate analysis demonstrated a significant relationship between CP-POPE healing time and sex, intraoperative blood loss, and type of pancreaticojejunostomy procedure. Multivariate Cox regression analysis using these factors revealed that intraoperative blood loss and type of pancreaticojejunostomy procedure were significant independent factors for the length of CR-POPF healing time. CR-POPF healing time following pancreaticoduodenectomy was 40.2±21.7 days on average (median, 35 days; range 10-110 days). Intraoperative blood loss and type of pancreaticojejunostomy procedure were identified as significant independent factors associated with the healing time. These results will help with earlier recovery from CR-POPF.

A 68-year-old woman was referred to our hospital with increased levels of biliary enzymes. On imaging, the patient was diagnosed with unresectable intrahepatic biliary tract cancer (BTC) with invasion of the portal vein and para-aortic lymph node metastasis (cT3N1M1, cStage IVb) and underwent endoscopic biliary drainage for the biliary stricture prior to therapy. The patient was subsequently enrolled in a phase III randomized trial (UMIN000014371/NCT02182778) and randomly assigned to receive gemcitabine/cisplatin/S-1 (GCS) combination therapy intravenously at doses of 1,000 or 25 mg/m2 on day 1 and orally twice daily at a dose of 80 mg/m2 on days 1–7 every 2 weeks. After 12 cycles of scheduled therapy without uncontrollable adverse effects, the patient achieved a good partial response with chemotherapy. Computed tomography (CT) revealed a marked reduction of the primary and metastatic lesions. In addition,18F-fluorodeoxyglucose-positron emission tomography/CT revealed diminishing abnormal uptake and no macroscopic evidence of factors adversely affecting tumor resectability. Therefore, the patient underwent extended right hepatic lobectomy, lymph node dissection and left hepaticojejunostomy. Finally, histological examination of the resected tissues revealed no residual cancer cells, suggesting a pathologically complete response. We herein present the case of a patient with intrahepatic BTC who achieved a pathologically complete response following combination chemotherapy with GCS.

Background Cholangiocarcinoma caused by exposure to 1,2-dichloropropane and/or dichloromethane is recognized as occupational cholangiocarcinoma. The aim of this study was to investigate the outcomes after resection of occupational cholangiocarcinoma to establish a treatment strategy for this disease. Methods Clinicopathological findings and outcomes after surgical intervention in 20 patients with occupational cholangiocarcinoma were investigated. Results Of 20 the patients, curative resection was performed in 16 patients. Three patients underwent radiation at the stump of the bile ducts. Adjuvant chemotherapy was performed in 12 patients. Biliary intraepithelial neoplasia, intraductal papillary neoplasm of the bile duct, and/or chronic bile duct injury was detected in most subjects. Intraabdominal infection developed after surgery in nine patients. Cholangiocarcinoma recurred in 12 of the 20 patients. The recurrent tumors in five patients developed at a different part of the bile duct from the primary tumor and a second resection was performed in four of these five patients. Conclusions The incidence of postoperative complications including intraabdominal infection was high in patients with occupational cholangiocarcinoma. Multicentric recurrence occurred not infrequently after surgery because the bile ducts had a high potential for the development of carcinoma. The aggressive treatment including second resection for the multicentric recurrence appeared to be effective.

Small-for-size graft syndrome is an inevitable complication in living donor liver transplantation (LDLT). We hypothesized that graft weight (GW) measured after graft procurement is one of the variables predicting postoperative graft function. A total of 138 consecutive recipients of adult-to-adult LDLT between March 1999 and October 2014 were included in this study. We investigated the factors associated with small-for-size-associated graft loss (SAGL) to determine the GW required for each patient. Both preoperatively assessed and postoperatively obtained risk factors for SAGL were analyzed in univariate and multivariate logistic regression analysis. Twelve (8.8%) of the transplant recipients had SAGL. In multivariate logistic regression analyses using preoperatively assessed variables, the preoperative Model for End-Stage Liver Disease (MELD) score (P < 0.001) and actual GW/recipient standard liver volume (SLV) ratio (P = 0.008) were independent predictors of SAGL. The recommended graft volume by preoperative computed tomography volumetry was calculated as SLV × (1.616 × MELD + 0.344)/100/0.85 (mL) [MELD ≥ 18.2], or SLV × 0.35 (mL) [MELD < 18.2]. The required allograft volume in LDLT can be determined by the preoperative MELD score of the recipient, and patients with higher MELD scores require larger grafts or deceased donor whole liver transplant to avoid SAGL. Liver Transplantation 22 599-606 2016 AASLD.