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Purpose: To evaluate the efficacy and safety of embolization with or without portal vein stenting for bleeding ectopic jejunal varices in the hepatopetal portal collateral due to extrahepatic portal vein occlusion or stenosis after hepatobiliary and pancreatic surgery. Materials and methods: This study included consecutive patients who underwent embolization for bleeding ectopic jejunal varices in the hepatopetal collateral due to extrahepatic portal vein occlusion or stenosis after hepatobiliary and pancreatic surgery between September 2012 and December 2020. The safety, technical and clinical success rates (no re-bleeding within 1 month) and re-bleeding-free survival after the first therapy and overall survival were assessed. Results: Fourteen sessions in 11 patients were included. Four patients (7 sessions) underwent variceal embolization only, and the remaining seven patients (7 sessions) underwent portal vein stenting and variceal embolization. Technical success was achieved in all 14 sessions (100%). Clinical success was achieved in 13 of 14 sessions (92.9%). No treatment-related serious complications including liver failure were observed. One-year and 2-year re-bleeding-free survival rate after the first endovascular therapy in all 11 patients was 90.9 and 60.6%, respectively. Two patients who experienced re-bleeding had repeat embolization treatment. There was no significant difference in re-bleeding-free survival after endovascular therapy between the combination with stenting and embolization group and the embolization-only group (p = 0.13). Conclusion: Embolization with or without portal vein stenting of bleeding ectopic jejunal varices in the hepatopetal portal collateral due to extrahepatic portal vein occlusion or stenosis after hepatobiliary and pancreatic surgery can be considered a safe, effective, and repeatable therapy for long-term hemostasis of uncontrollable bleeding. [ABSTRACT FROM AUTHOR]

Pancreaticobiliary maljunction (PBM) is a congenital malformation. The reflux of pancreatic juice into the biliary tract caused by PBM plays a significant role in the development of biliary tract cancers (BTCs), such as gallbladder cancer and cholangiocarcinoma. Previous studies have demonstrated a high incidence of BTC in patients with PBM. However, there are only a few reports of patients who developed BTC after a diagnosis of PBM. We report the cases of two patients who developed gallbladder cancer after being diagnosed with PBM. They had refused treatment and were being managed with follow-up observation alone after the diagnosis of PBM and developed gallbladder cancer after several years of observation. Thus, surgical treatment should be recommended for all patients with PBM in order to prevent the development of BTC. Moreover, long-term, close, regular follow-up is necessary to facilitate the early diagnosis of subsequent BTC in patients with untreated PBM. [ABSTRACT FROM AUTHOR]

Cholangiocarcinoma (CC) has a poor prognosis and different driver genes depending on the site of onset. Intrahepatic CC is the second‐most common liver cancer after hepatocellular carcinoma, and novel therapeutic targets are urgently needed. The present study was conducted to identify novel therapeutic targets by exploring differentially regulated genes in human CC. MicroRNA (miRNA) and mRNA microarrays were performed using tissue and serum samples obtained from 24 surgically resected hepatobiliary tumor cases, including 10 CC cases. We conducted principal component analysis to identify differentially expressed miRNA, leading to the identification of miRNA‐3648 as a differentially expressed miRNA. We used an in silico screening approach to identify its target mRNA, the tumor suppressor Sloan Kettering Institute (SKI). SKI protein expression was decreased in human CC cells overexpressing miRNA‐3648, endogenous SKI protein expression was decreased in human CC tumor tissues, and endogenous SKI mRNA expression was suppressed in human CC cells characterized by rapid growth. SKI‐overexpressing OZ cells (human intrahepatic CC cells) showed upregulation of cyclin‐dependent kinase inhibitor p21 mRNA and protein expression and suppressed cell proliferation. Nuclear expression of CDT1 (chromatin licensing and DNA replication factor 1), which is required for the G1/S transition, was suppressed in SKI‐overexpressing OZ cells. SKI knockdown resulted in the opposite effects. Transgenic p21‐luciferase was activated in SKI‐overexpressing OZ cells. These data indicate SKI involvement in p21 transcription and that SKI–p21 signaling causes cell cycle arrest in G1, suppressing intrahepatic CC cell growth. Therefore, SKI may be a potential therapeutic target for intrahepatic CC. [ABSTRACT FROM AUTHOR]

Background: This study is aimed to compare the occurrence of postoperative infections between patients with hepatocellular carcinoma (HCC) undergoing laparoscopic liver resection (LLR) and those undergoing open liver resection (OLR).Methods: This study included 446 patients who underwent initial curative liver resection for HCC 5 cm or less in size without macroscopic vascular invasion. To adjust for confounding factors between the LLR and OLR groups, propensity score matching and inverse probability weighting (IPW) analysis were performed. The incidence rates of postoperative infection, including incisional surgical site infection (SSI), organ/space SSI, and remote infection (RI), were compared between the two groups.Results: An imbalance in several confounding variables, including period of surgery, extent of liver resection, difficult location, proximity to a major vessel, tumor size ≥ 3 cm, and multiple tumors, was observed between the two groups in the original cohort. After matching and weighting, the imbalance between the two groups significantly decreased. Compared with OLR, LLR was associated with a lower volume of intraoperative blood loss (140 vs. 350 mL, P < 0.001 in the matched cohort; 120 vs. 320 mL, P < 0.001 in the weighted cohort) and reduced risk of postoperative infection (2.0% vs. 12%, P = 0.015 in the matched cohort; 2.9% vs. 14%, P = 0.005 in the weighted cohort). Of the types of postoperative infections, organ/space SSI and RI were less frequently observed in the LLR group than in the OLR group in the matched cohort (1.0% vs. 6.0%, P = 0.091 for organ/space SSI; 0% vs. 6.0%, P < 0.001 for RI) and in the weighted cohort (1.2% vs. 7.8%, P < 0.001 for organ/space SSI; 0.3% vs. 5.1%, P = 0.009 for RI).Conclusions: Compared with OLR, LLR for HCC might reduce postoperative infections, including organ/space SSI and RI. [ABSTRACT FROM AUTHOR]

Background and Aim: We evaluated the efficacy of rechallenge transcatheter arterial chemoembolization (TACE) after lenvatinib (LEN) treatment in patients with previous TACE failure/refractoriness. Methods: We enrolled 63 consecutive patients with a history of TACE failure/refractoriness prior to LEN treatment as a first‐line systemic therapy. We reviewed the clinical backgrounds and courses of the patients. Results: In total, 25 patients underwent rechallenge TACE after LEN due to LEN‐refractoriness (17 cases) or intolerance (8 cases). A complete or partial response was obtained for 13 (65.0%) of the 20 patients whose therapeutic effects were determined. The survival rate of patients who underwent rechallenge TACE was significantly higher than that of patients who did not undergo rechallenge TACE (median survival time, not reached vs 403 days, P = 0.015). Rechallenge TACE significantly reduced the risk of death in univariate (hazard ratio [HR] 0.24, 95% confidence interval [CI] 0.08–0.69, P = 0.008) and multivariate analyses (HR 0.26, 95% CI 0.08–0.80, P = 0.019). If complete or partial response was obtained by rechallenge TACE, the median survival time of these patients was significantly longer than those of the progressive disease (PD) group (P = 0.05), and the median survival time of the PD group after rechallenge TACE was not different from that of the group who did not undergo rechallenge TACE (P = 0.36). We did not observe a decrease in the ALBI score after TACE. Conclusion: Rechallenge TACE after LEN is an effective treatment that may result in a favorable prognosis. [ABSTRACT FROM AUTHOR]

Background: This study aimed to determine the risk factors for severe postoperative complications in patients undergoing pure laparoscopic liver resection (LLR) for tumors in the right posterosuperior (PS) segments. Methods: The study included 289 patients who underwent parenchyma‐sparing pure LLR for tumors in the right PS segments at eight treatment centers between January 2009 and December 2019. Results: Multivariate analysis revealed tumor size ≥3 cm (P =.016), segmentectomy (P =.044), and liver cirrhosis (P =.029) as independent risk factors for severe postoperative complications. The severe complication rates (2.7% vs 12.1%, P =.0025), median intraoperative blood loss (100 mL vs 150 mL, P =.001), and median operation time (248 minutes vs 299.5 minutes, P =.0013) were lower in the patients without all these three risk factors than those with at least one risk factor. The median length of postoperative hospital stay was shorter in patients with no risk factors than those with at least one risk factor (9 days vs. 10 days, P =.001). Conclusions: Tumor size ≥3 cm, segmentectomy, and liver cirrhosis were the risk factors for severe postoperative complications after parenchyma‐sparing pure LLR for tumors in the right PS segments. Patients without these three risk factors would be appropriate candidates for safely performing parenchyma‐sparing pure LLR in the right PS segments at the outset. [ABSTRACT FROM AUTHOR]

Background: The effectiveness and extent of regional lymph node dissection in primary duodenal cancer (DC) remains unclear. This study aimed to analyze the prognostic factors and lymph node metastasis (LNM) patterns in DC. Methods: Fifty-three patients who underwent surgical resection for DC between January 1998 and December 2018 at two institutions were retrospectively analyzed. Univariate and multivariate analyses were performed on the prognostic factors of resected DC. Moreover, the relationships between depth of tumor invasion and incidence of LNM and between tumor location and LNM stations were analyzed. Results: The five-year survival rate of the study population was 68.9%. Multivariate survival analysis demonstrated that histologic grade G2–G4, presence of LNM, pT3–4, and elevated preoperative CA19-9 were the independent poor prognostic factors. No patient with pTis–T2 had LNM. On the other hand, LNM was found in 70% of patients with pT3–4. Among 36 patients who underwent pancreaticoduodenectomy (PD), LNM around the pancreatic head was observed, regardless of the duodenal cancer site, including the duodenal bulb and the third to the fourth portion. Conclusions: Histologic grade G2–G4, presence of LNM, pT3–T4, and elevated preoperative CA19-9 were the independent poor prognostic factors in patients with resected DC. Our results suggested that lymph node dissection could be omitted for DC Tis–T1a. Moreover, based on the high frequency of LNM in T3–4 cases, PD with lymph node dissection in the pancreatic head region was considered necessary for T3–4 DC at any site. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to elucidate the effects of laparoscopic liver resection (LLR) vs open liver resection (OLR) for major complications (Clavien‐Dindo classification grade ≥ IIIa) in obese individuals with hepatocellular carcinoma (HCC). Methods: The clinical records of 339 and 733 patients who underwent LLR and OLR, respectively, for HCC between 2000 and 2019 were retrospectively reviewed. Body mass index (BMI) groups were classified according to the definitions of the World Health Organization: underweight group, BMI ≤ 18.4 kg/m2 (LLR vs OLR: 27 vs 47); normal weight, BMI 18.5‐24.9 kg/m2 (211 vs 483); overweight, BMI 25.0‐29.9 kg/m2 (85 vs 181); and obese, BMI ≥ 30.0 kg/m2 (16 vs 22). The effects of obesity on major complications after LLR and OLR were investigated. Results: In total, 18 (5.3%) and 127 (17.3%) patients presented with major complications after LLR and OLR, respectively. There was no significant difference in the incidence of major complications after OLR in the four BMI groups. However, a stepwise decrease in the incidence of major complications after LLR was observed from the underweight to the obese group. In addition, a multivariate analysis revealed that increased BMI was an independent preventive factor for major complications after LLR (P =.026, odds ratio: 0.84). The estimated adjusted risk of major postoperative complications decreased with increased BMI in the LLR group, while the risk did not decrease in the OLR group (P for interaction =.048). Conclusion: Laparoscopic liver resection is beneficial for obese patients and is superior to OLR. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to evaluate the indications of laparoscopic repeat liver resection (LRLR) for recurrent hepatocellular carcinoma from the viewpoint of its difficulty. Methods: One hundred and one patients who underwent LRLR and 59 patients who underwent open repeat liver resection (ORLR) were included. The difficulty was classified according to the preoperative predictive factors for difficult LRLR, including an open approach during previous liver resection, history of two or more previous liver resections, history of previous major liver resection, tumor near the resected site of the previous liver resection, and intermediate or high difficulty with the difficulty scoring system. We compared the surgical outcomes between the LRLR and ORLR groups based on the difficulty class (low‐ or intermediate difficiulty class, 0 to 3 predictive factors; high difficiulty class, 4 or 5 factors). Results: In the low‐ or intermediate difficiulty class, intraoperative blood loss and the proportion of patients with postoperative complications were significantly lower in LRLR than in ORLR, and the duration of the postoperative hospital stay was significantly shorter in LRLR than in ORLR. In the high difficiulty class, total operative time and operative time before starting hepatic parenchymal resection were significantly longer in LRLR than in ORLR, and there were no significant differences in other surgical outcomes between the two groups. Conclusion: LRLR is recommended for patients in the low or intermediate difficulty class. However, LRLR does not have an advantage with longer operative time for patients in the high difficulty class compared with ORLR. [ABSTRACT FROM AUTHOR]

Background: Despite the recently increasing number of elderly patients undergoing liver resection, the impact of advancing age on postoperative infections (PIs) incidence and risk remains unclear. This study aimed to investigate the impact of advancing age on PIs incidence and status. Methods: This retrospective study included 744 patients undergoing liver resection without biliary reconstruction or combined resection of other organs. Multivariable analysis with a restricted cubic spline was used to evaluate the impact of advancing age on PIs and to determine its association with PIs risk in patients undergoing open and laparoscopic liver resection (OLR and LLR, respectively). Results: Multivariable analysis demonstrated that advancing age was significantly associated with increased PIs risk (P = 0.017). The spline curve showed that the odds ratio for PIs sharply increased starting approximately at 65 years of age. Unadjusted restricted cubic splines assessing the subcategories of PIs demonstrated that advancing age was associated with increased risks of organ/space surgical site infection and sepsis (P = 0,064 and 0.048, respectively). Multivariable analysis revealed that LLR was associated with the lower PIs risk compared with OLR (P = 0.025), whereas the lower PIs risk with LLR was not significantly obscured by advancing age (P = 0.29). Conclusions: Advancing age was associated with increased risk of PIs, including organ/space surgical site infections and sepsis, after liver resection especially in patients aged ≥ 65 years. [ABSTRACT FROM AUTHOR]

Aim: We investigated effects of direct‐acting antiviral (DAA)–induced sustained virological response (SVR) after liver resection in patients with hepatitis C virus (HCV)–related hepatocellular carcinoma (HCC) for postoperative recurrence and survival. Methods: Surgical outcomes in 18 patients with postoperative DAA‐induced SVR (HCC‐DAA group) were compared with those in 23 patients with preoperative DAA‐induced SVR (DAA‐HCC group) and those in 10 patients who did not receive DAA therapy (control group). Patients who received DAA therapy >1 year after surgery and those with recurrence <1 year after surgery were excluded. Results: Serum concentrations of aminotransferases improved 1 year after surgery in both the HCC‐DAA and DAA‐HCC groups. The number of HCC‐DAA patients with albumin‐bilirubin (ALBI) grade 1 increased from 11 to 15. The disease‐free survival rate did not differ between HCC‐DAA group (3 years, 60%) and the other two groups (DAA‐HCC group, 92% and control group, 60%). The 3‐year overall survival rates were better in the DAA‐HCC group (84%) and HCC‐DAA group (100%) than in the control group (46%; all ps < 0.05 according to Holm's test). Multivariable analysis revealed that tumor stage was an independent risk factor for postoperative recurrence, and ALBI grade at 1 year after surgery was predictive of postoperative survival, but DAA‐induced SVR was neither. Conclusions: Although postoperative DAA‐induced SVR itself may not suppress postoperative recurrence, improvement in liver function as a result of DAA administration after surgery may prolong postoperative survival. [ABSTRACT FROM AUTHOR]

Introduction: The present study aimed to evaluate the effect of poor differentiation and tumor size on survival outcome after hepatic resection of hepatocellular carcinoma (HCC). Methods: A total of 1,107 patients who underwent initial and curative hepatic resection for HCC without macroscopic vascular invasion participated in the study. Using the multivariable Cox proportional hazards regression model, we evaluated changes in hazard ratios (HRs) for the association between tumor differentiation and survival based on tumor size. Results: In patients with poorly (Por) differentiated HCCs, the adjusted HRs of reduced overall survival (OS), recurrence-free survival (RFS), early RFS, and early extrahepatic RFS were 1.31 (95% confidence interval [CI]; 1.07–1.59), 1.07 (95% CI 0.89–1.28), 1.31 (95% CI 1.06–1.62), and 1.81 (95% CI 1.03–3.17), respectively. Moreover, based on an analysis of the effect modification of tumor differentiation according to tumor size, Por HCC was found to be associated with a reduced OS (p = 0.033). The HRs of Por HCCs sharply increased in patients with tumors measuring up to 5 cm. The adjusted HRs of reduced OS in patients with Por HCCs measuring <2, ≥2 and <5, and ≥5 cm were 1.22 (95% CI 0.69–2.14), 1.33 (95% CI 1.02–1.73), and 1.58 (95% CI 1.04–2.42), respectively. The corresponding adjusted HRs of reduced early RFS were 0.85 (95% CI 0.46–1.57), 1.34 (95% CI 1.01–1.8), and 1.57 (95% CI 1.03–2.39), respectively. The adjusted HRs of reduced early extrahepatic RFS were 1.89 (95% CI 0.83–4.3) in patients with tumors measuring ≥2 and <5 cm and 2.33 (95% CI 0.98–5.54) in those with tumors measuring ≥5 cm. Conclusions: Por HCC measuring ≥2 cm was associated with early recurrence. Hence, it had negative effects on OS. After surgery, patients with Por HCC measuring ≥5 cm should be cautiously monitored for early extrahepatic recurrence. These findings will help physicians devise treatment strategies for patients with HCC. [ABSTRACT FROM AUTHOR]

Introduction: The present study aimed to evaluate the effect of poor differentiation and tumor size on survival outcome after hepatic resection of hepatocellular carcinoma (HCC). Methods: A total of 1,107 patients who underwent initial and curative hepatic resection for HCC without macroscopic vascular invasion participated in the study. Using the multivariable Cox proportional hazards regression model, we evaluated changes in hazard ratios (HRs) for the association between tumor differentiation and survival based on tumor size. Results: In patients with poorly (Por) differentiated HCCs, the adjusted HRs of reduced overall survival (OS), recurrence-free survival (RFS), early RFS, and early extrahepatic RFS were 1.31 (95% confidence interval [CI]; 1.07–1.59), 1.07 (95% CI 0.89–1.28), 1.31 (95% CI 1.06–1.62), and 1.81 (95% CI 1.03–3.17), respectively. Moreover, based on an analysis of the effect modification of tumor differentiation according to tumor size, Por HCC was found to be associated with a reduced OS (p = 0.033). The HRs of Por HCCs sharply increased in patients with tumors measuring up to 5 cm. The adjusted HRs of reduced OS in patients with Por HCCs measuring <2, ≥2 and <5, and ≥5 cm were 1.22 (95% CI 0.69–2.14), 1.33 (95% CI 1.02–1.73), and 1.58 (95% CI 1.04–2.42), respectively. The corresponding adjusted HRs of reduced early RFS were 0.85 (95% CI 0.46–1.57), 1.34 (95% CI 1.01–1.8), and 1.57 (95% CI 1.03–2.39), respectively. The adjusted HRs of reduced early extrahepatic RFS were 1.89 (95% CI 0.83–4.3) in patients with tumors measuring ≥2 and <5 cm and 2.33 (95% CI 0.98–5.54) in those with tumors measuring ≥5 cm. Conclusions: Por HCC measuring ≥2 cm was associated with early recurrence. Hence, it had negative effects on OS. After surgery, patients with Por HCC measuring ≥5 cm should be cautiously monitored for early extrahepatic recurrence. These findings will help physicians devise treatment strategies for patients with HCC. [ABSTRACT FROM AUTHOR]

Background: Although several risk factors for incisional hernia after hepatectomy have been reported, their relationship to different wound sites has not been investigated. Therefore, this study aimed to examine the risk factors for incisional hernia according to various wound sites after hepatectomy. Methods: Patients from the Osaka Liver Surgery Study Group who underwent open hepatectomy using combinations of vertical and horizontal incisions (J‐shaped incision, reversed L‐shaped incision, reversed T‐shaped incision, Mercedes incision) between January 2012 and December 2015 were included. Incisional hernia was defined as a hernia occurring within 3 y after surgery. Abdominal incisional hernia was classified into midline incisional hernia and transverse incisional hernia. The risk factors for each posthepatectomy incisional hernia type were identified. Results: A total of 1057 patients met the inclusion criteria. The overall posthepatectomy incisional hernia incidence rate was 5.9% (62 patients). In the multivariate analysis, the presence of diabetes mellitus and albumin levels <3.5 g/dL were identified as independent risk factors. Moreover, incidence rates of midline and transverse incisional hernias were 2.4% (25 patients), and 2.3% (24 patients), respectively. In multivariate analysis, the independent risk factor for transverse incisional hernia was the occurrence of superficial or deep incisional surgical site infection, and interrupted suturing for midline incisional hernia. Conclusions: Risk factors for incisional hernia after hepatectomy depend on the wound site. To prevent incisional hernia, running suture use might be better for midline wound closure. The prevention of postoperative wound infection is important for transverse wounds, under the presumption of preoperative nutrition and normoglycemia. [ABSTRACT FROM AUTHOR]

Although it has recently been reported that immune checkpoint inhibitors (ICIs) constitute effective treatment for solid tumors, the success rate in patients with intrahepatic cholangiocarcinoma is limited. We administered pembrolizumab to a patient as treatment for liver and lymph node metastases of intrahepatic cholangiocarcinoma. The patient had abundant infiltration of programmed death ligand 1-positive macrophages, cytotoxic T cells (CD8-positive lymphocytes), and programmed death 1-positive lymphocytes as well as a high combined positive score of 33.1, high-frequency microsatellite instability, and mismatch repair deficiency. These characteristics are predictive biomarkers of the efficacy of ICIs. After pembrolizumab was administered four times (triweekly administration), the carbohydrate antigen 19–9 serum level fell within the normal range, and computed tomography revealed that the size of the metastatic liver tumors and enlarged hilar lymph node had markedly decreased. However, the patient developed pruritus and exanthema on the trunk and limbs after 14 administrations and was diagnosed with bullous pemphigoid. We discontinued pembrolizumab therapy and started treatment for bullous pemphigoid. Nine months after discontinuation of pembrolizumab therapy, the patient remains alive without tumor relapse. This patient had durable response even after discontinuation of pembrolizumab therapy for multiple metastases of intrahepatic cholangiocarcinoma. [ABSTRACT FROM AUTHOR]

Background: Vascular invasion involving a tumor thrombus in the inferior vena cava and/or right atrium is an unfavorable prognostic factor after intrahepatic cholangiocarcinoma resection. We report an intrahepatic cholangiocarcinoma case with a tumor thrombus extending from the left hepatic vein via the inferior vena cava to the right atrium. Case presentation: A 58-year-old man with epigastralgia was referred to our hospital after an emergent transcatheter arterial embolization was done following the radiological diagnosis of a ruptured hepatic tumor. The serum concentrations of carcinoembryonic antigen, carbohydrate 19-9, duke pancreatic monoclonal antigen type 2, and cytokeratin-19 fragments were elevated; meanwhile those of alfa-fetoprotein and des-γ-carboxy prothrombin were within normal ranges. A contrast-enhanced computed tomography scan showed a heterogeneously enhanced tumor, 13 cm in diameter, in the left lobe of the liver, enlarged lymph nodes along the lesser curvature of the stomach, and a tumor thrombus extending from the left hepatic vein via the inferior vena cava to the right atrium. We performed a left hemihepatectomy and tumor thrombectomy under total hepatic vascular exclusion to reduce the risk of sudden death. After dissection of the liver parenchyma along the left side of the middle hepatic vein, except for the left hepatic vein, the inferior vena cava just below the right atrium could be clamped by pulling down the left lobe of the liver toward the caudal side. The thrombus could be removed by incising the inferior vena cava under total hepatic vascular exclusion. Microscopic examination showed a tubular adenocarcinoma. Immunohistochemical staining was positive for cytokeratin-7, cytokeratin-19, and epithelial membrane antigen, but negative for arginase-1, glypican-3, and hepatocyte. The patient was pathologically diagnosed with an intrahepatic cholangiocarcinoma with a tumor thrombus in the inferior vena cava. Adjuvant chemotherapy with tegafur/gimeracil/oteracil was administered for 1 year. The patient remained in good health without cancer recurrence for over 4 years after the operation. Conclusion: An aggressive surgical approach may be indicated for intrahepatic cholangiocarcinoma with a tumor thrombus in the inferior vena cava and/or right atrium to avoid the risk of impending death. [ABSTRACT FROM AUTHOR]

Background: Occupational cholangiocarcinoma (CCA) was first described in patients who were working at a printing company in Osaka, Japan. Recently, the therapeutic efficacy and safety of a PD1 inhibitor nivolumab are being evaluated in patients with occupational CCA in an investigator‐initiated clinical trial. The therapeutic effects of immune checkpoint inhibitors are closely associated with immune cells. Methods: Immunohistochemical analysis was performed to characterize immune cells in the tumor microenvironment of occupational CCA. The status of mismatch repair (MMR)/microsatellite instability (MSI) was also examined. Results: The tumor stroma of occupational CCA was characterized by abundant infiltration of immune cells expressing CD3, CD4, CD8, CD163, FOXP3, and granzyme B. Additionally, lymphocytes expressing immune checkpoint receptors, such as PD1, CTLA4, LAG3, TIM3, and TIGIT, were frequently infiltrated. The loss of immunohistochemical expression of the MMR proteins (MLH1, MSH2, PMS2, and MSH6) was not observed in cases of occupational CCA, and MSI was not detected. Conclusions: The tumor microenvironment of occupational CCA had features of immunosuppression, and the occurrence of T‐cell dysfunction or exhaustion was suggested. The results provide supportive evidence for the efficacy of immune checkpoint inhibitor therapy for this disease. [ABSTRACT FROM AUTHOR]

Background: This study aimed to evaluate the impact of the age-adjusted Charlson comorbidity index (ACCI) on outcomes after hepatic resection for hepatocellular carcinoma (HCC). Methods: We assessed 763 patients who underwent hepatic resection for HCC. The ACCI scores were categorized as follows: ACCI ≤ 5, ACCI = 6, and ACCI ≥ 7. Results: A multivariate analysis showed that the odds ratios for postoperative complications in ACCI = 6 and ACCI ≥ 7 groups, with reference to ACCI ≤ 5 group, were 0.71 (p = 0.41) and 4.15 (p < 0.001), respectively. The hazard ratios for overall survival of ACCI = 6 and ACCI ≥ 7 groups, with reference to ACCI ≤ 5 group, were 1.52 (p = 0.023) and 2.45 (p < 0.001), respectively. The distribution of deaths due to HCC-related, liver-related, and other causes was 68.2%, 11.8%, and 20% in ACCI ≤ 5 group, 47.2%, 13.9%, and 38.9% in ACCI = 6 group, and 27.3%, 9.1%, and 63.6% in ACCI ≥ 7 group (p = 0.053; ACCI ≤ 5 vs. = 6, p = 0.19; ACCI = 6 vs. ≥ 7, p < 0.001; ACCI ≤ 5 vs. ≥ 7). In terms of the treatment for HCC recurrence in ACCI ≤ 5, ACCI = 6, and ACCI ≥ 7 groups, adaptation rate of surgical resection was 20.1%, 7.3%, and 11.1% and the rate of palliative therapy was 4.3%, 12.2%, and 22.2%, respectively. Conclusions: The ACCI predicted the short-term and long-term outcomes after hepatic resection of HCC. These findings will help physicians establish a treatment strategy for HCC patients with comorbidities. [ABSTRACT FROM AUTHOR]

Background/Purpose: Aeromonas hydrophila can cause lethal infectious complications after surgery. There have been no large cohort studies of this specific to the hepato‐biliary‐pancreatic (HBP) field. We investigate the postoperative influence of A hydrophila infection after HBP surgery. Methods: We retrospectively reviewed patients who underwent HBP surgery between 2008 and 2017 at eight university hospitals. Patients with A hydrophila isolation during perioperative management were extracted, and their postoperative courses were investigated. Results: Bacterial culture examination of 10 074 patients was performed as perioperative management. Among them, 76 patients (0.75%) had A hydrophila isolation, most of whom underwent pancreatoduodenectomy (n = 38) or hepatectomy with biliary reconstruction (n = 14). There were seven mortalities after these two procedures (13.5%), five within 3 days after the onset of infection. Bile (n = 48) and abdominal drainage fluid (n = 29) were major sites of A hydrophila isolation. Typical prophylactic antibiotics, cefazolin or flomoxef, were mostly resistant. There was no mortality among patients that received sensitive antibiotics prophylactically. Conclusions: Isolation of A hydrophila was low in our cases of HBP surgery, but the condition of some patients deteriorated rapidly by this infection. Although there could be several bacterial infections during management of HBP surgery, A hydrophila should not be overlooked. Preparation of appropriate prophylactic antibiotics may prevent or reduce mortality. [ABSTRACT FROM AUTHOR]

Background: This study aimed to evaluate the prognostic impact of the 5‐5‐500 rule in patients after hepatic resection for the intermediate stage of hepatocellular carcinoma (HCC; The Barcelona Clinic Liver Cancer classification [BCLC] B). Methods: 177 patients had hepatic resection for BCLC‐B HCC. The 5‐5‐500 rule was defined by tumor size ≤5 cm in diameter, tumor number ≤5, and α‐fetoprotein ≤500 ng/mL. Results: The 3‐, 5‐, and 7‐year recurrence‐free survival rates were 22%, 14%, and 11% in patients within the 5‐5‐500 rule, and 16%, 10%, and 10% in patients beyond the 5‐5‐500 rule, respectively (P =.015). The 3‐, 5‐, and 7‐year overall survival rates were 72%, 47%, and 34% in patients within the 5‐5‐500 rule, and 52%, 31%, and 25% in patients beyond the 5‐5‐500 rule, respectively (P =.035). Being beyond the 5‐5‐500 rule and liver cirrhosis were independent prognostic factors for recurrence‐free survival. For overall survival, being beyond the 5‐5‐500 rule, age ≥65 years, Child–Pugh class B, and anti‐hepatitis C antibody positive were identified as independent prognostic factors. Conclusions: The 5‐5‐500 rule could predict prognosis in BCLC‐B patients with hepatic resection. Hepatic resection might provide survival benefit for selected patients with BCLC‐B HCC within the 5‐5‐500 rule. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to evaluate survival outcomes in patients with non-B non-C hepatocellular carcinoma (NBNC-HCC) with reference to patients with HCC achieving sustained virological response (SVR) by preoperative interferon (IFN) treatment for chronic hepatitis C.Methods: We examined 781 patients who underwent hepatic resection for HCC. They were classified into NBNC-HCC, SVR-HCC, and non-SVR HCC groups.Results: Multivariate analysis for recurrence-free survival (RFS) and overall survival (OS) revealed that the adjusted hazard ratios (HR) of NBNC-HCC and non-SVR HCC groups with reference to the SVR-HCC group were 1.46 (p = 0.10) and 2.10 (p < 0.001), respectively, for RFS, and 1.69 (p = 0.024) and 2.11 (p < 0.001), respectively, for OS. Worsening of Child-Pugh grade at recurrence was confirmed in 21 patients (17.1%) with NBNC-HCC but not in those with SVR-HCC (p = 0.017, SVR vs. NBNC). In the NBNC-HCC group, hepatic resection for intrahepatic recurrence was adopted in 17.4% of patients without worsening of Child-Pugh grade at recurrence, whereas hepatic resection was not adopted in those with grade worsening. Among patients with alcoholic hepatitis, Child-Pugh grade worsening at recurrence was more frequently observed in patients with sobriety than those without sobriety (14.3% vs. 46.2%, p = 0.049).Conclusions: NBNC-HCC patients had an increased risk for overall death as compared with those with SVR-HCC. Worsening of background liver function may reduce the chances of re-hepatic resection for recurrence and increase the risk for overall death in NBNC-HCC patients. For alcoholic hepatitis patients, sobriety may prevent deterioration of liver function after surgery. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to investigate the predictive factors and classifications for difficulty of laparoscopic repeated liver resection (LRLR) in patients with recurrent hepatocellular carcinoma. Methods: Sixty patients who underwent LRLR were included. Potential predictive factors for difficult LRLR included the approach of the previous liver resection (laparoscopic or open), the number of previous liver resections, a history of cholecystectomy in previous liver resection, the operative procedure of previous liver resection, whether the tumor was near the resected site of the previous liver resection, non‐surgical treatments before the present surgery, and the difficulty scoring system for laparoscopic liver resection. The relationship between these factors and perioperative outcomes were evaluated to investigate the predictive factor for difficult LRLR. Results: Univariate and multivariate analyses demonstrated that an open approach during previous liver resection, two or more previous liver resections, a history of previous liver resection with not less than sectionectomy, tumor near the resected site of the previous liver resection, and intermediate or high difficulty in the difficulty scoring system were independent risk factors for prolonged operative time and/or severe adhesion of LRLR. Three difficulty classifications were then suggested based on the number of these five predictive factors. The difficulty classification reflected operative time, intraoperative blood loss, and incidence of postoperative complication. Conclusion: The difficulty of LRLR may be predicted by three difficulty classifications using five preoperative predictive factors. [ABSTRACT FROM AUTHOR]

Purpose: We assessed the association of tumor size with patient survival following diagnosis of solitary hepatocellular carcinoma without vascular invasion.Methods: The overall population comprised 638 patients who initially underwent hepatic resection with curative intent for a solitary hepatocellular carcinoma without macroscopic vascular invasion (487 had no microscopic vascular invasion). We set 5 cm as the tumor cutoff size for a solitary tumor based on the Milan criteria, and we used a multivariate Cox proportional hazards model and propensity score matching to evaluate the impact of tumor size on survival.Results: Tumor size was significantly associated with a proportional increase in cancer-specific survival in the overall population (P = 0.001) and the subgroup with no microscopic vascular invasion (P = 0.029); however, multivariate analysis revealed no significant risk associated with recurrence-free survival (P = 0.055 and 0.59, respectively). After propensity score matching, the cancer-specific survival of patients with tumors > 5 cm was significantly worse than for those with tumors ≤ 5 cm in the overall population (P = 0.0077); the corresponding 2-year cumulative recurrence rates were 45.8% and 23.5%, respectively (P = 0.0027). Finally, the proportions of extrahepatic to total recurrences were 8% for those with tumors ≤ 5 cm and 29.1% for those with tumors > 5 cm in the unmatched overall population (P < 0.001).Conclusion: Tumor size was associated with recurrence within 2 years of surgery and with poor cancer-specific survival in patients with solitary hepatocellular carcinoma, even in the absence of microscopic vascular invasion. [ABSTRACT FROM AUTHOR]

Recently identified occupational cholangiocarcinoma among printing workers is characterized by chronic bile duct injuries and precancerous or early cancerous lesions at multiple sites of the bile ducts. These observations suggested the potential multifocal carcinogenesis of the disease. We performed whole-exome analysis of multiple lesions, including the invasive carcinomas and precancerous lesions of four occupational cholangiocarcinoma cases. A much higher mutation burden was observed in both the invasive carcinomas (mean 76.3/Mb) and precancerous lesions (mean 71.8/Mb) than in non-occupational cholangiocarcinomas (mean 1.6/Mb). Most somatic mutations identified in 11 of 16 lesions did not overlap with each other. In contrast, a unique trinucleotide mutational signature of GpCpY to GpTpY was shared among the lesions. These results suggest that most of these lesions are multiclonal in origin and that common mutagenic processes, which may be induced by exposure to haloalkanes or their metabolites, generated somatic mutations at different sites of the bile ducts. A similarly high mutation rate had already been identified in the precancerous lesions, implying an increased potential for carcinogenesis throughout the biliary tree. These genomic features support the importance of ongoing close follow-up of the patients as a group at high risk of recurrence. [ABSTRACT FROM AUTHOR]

Introduction: We investigated the indications for laparoscopic liver resection (LLR) of mass‐forming intrahepatic cholangiocarcinoma (MF‐ICC), including the need for lymph node dissection for improved postoperative prognosis. Methods: This study involved 36 patients who underwent surgery for solitary peripheral MF‐ICC. Fifteen patients underwent LLR, and 21 underwent open liver resection (OLR). Surgical outcomes and prognostic factors were investigated to determine the indications for LLR. Results: No significant differences were observed in perioperative outcomes between patients who underwent LLR and OLR. A significantly worse disease‐free survival (DFS) rate was observed in patients who preoperatively had a tumor diameter ≥3 cm, vascular invasion on diagnostic imaging, and elevated serum carbohydrate antigen (CA) 19‐9 and carcinoembryonic antigen (CEA) levels. A significantly worse overall survival (OS) rate was observed in patients with a tumor diameter ≥3 cm, vascular invasion on diagnostic imaging, and elevated serum CA19‐9 levels. Therefore, a tumor diameter ≥3 cm, vascular invasion on diagnostic imaging, and elevated serum CA19‐9 and CEA levels were determined to be preoperative prognostic factors. DFS and OS rates were significantly better in patients without these factors. Moreover, in six patients without these factors who underwent LLR, neither lymph node metastasis nor postoperative recurrence was observed. Conclusion: A tumor diameter ≥3 cm, vascular invasion on diagnostic imaging, and elevated serum CA19‐9 and CEA levels are preoperative prognostic factors for peripheral MF‐ICC. LLR is indicated for patients without these factors. [ABSTRACT FROM AUTHOR]

Introduction: We conducted a retrospective study to investigate the progress of the operative outcome after laparoscopic splenectomy (LS), with a special reference to the administration of prophylactic antibiotics (PA). Methods: The study included 123 patients who underwent elective LS. Operative outcomes before and after the operative procedure was standardized and the impact of treatment with PA on surgical‐site infection were investigated. Results: With regard to complications, wound infection developed in one (0.8%), portal trunk thrombosis in one (0.8%), pancreatic fistula in one (0.8%), postoperative bleeding in two (1.6%), pleural effusion in one (0.8%), and reoperation because of bowel injury in one (0.8%). Although morbidity did not differ between patients in the early (until the end of 2010) and late (after the beginning of 2011) periods, intraoperative blood loss was lower in patients in the late period. During the late period, no patients required conversion to open surgery. The proportion of patients with surgical‐site infection did not differ between those who received PA 1 h before the start of surgery and every 3 h during surgery and those who received PA 1 h before the start of surgery, every 3 h during surgery, and twice a day for 24–72 h after surgery. Conclusion: Operative outcomes after LS improved after the standardization of the operative procedure. The administration of PA 1 h before surgery and every 3 h during surgery seems to be sufficient to prevent surgical‐site infection during LS. [ABSTRACT FROM AUTHOR]

Aim: The 2016 guidelines of the Japan Society for Surgical Infection and the Japan Society of Chemotherapy advocate giving prophylactic antibiotics 1 hour before surgery and until 24 hours after surgery in patients undergoing elective hepatic resection. However, the efficacy of short‐term antimicrobial prophylaxis has not been evaluated according to surgical approach. We evaluated the efficacy of giving prophylactic antibiotics in patients undergoing open or laparoscopic hepatic resection. Methods: The study comprised 218 and 185 patients undergoing open and pure laparoscopic hepatic resection, respectively. Incidence rates of postoperative infectious complications were compared between patients who received flomoxef sodium as the prophylactic antibiotic before and until 24 hours after surgery (short‐term group) and those who received flomoxef sodium until 72 hours after surgery (long‐term group) among patients undergoing open or laparoscopic hepatic resection. Propensity score matching analysis was carried out to adjust for confounding factors between the short‐ and long‐term groups. Results: There was no significant difference in the postoperative infectious complication incidence between the short‐ and long‐term groups among patients undergoing open (18.9% vs 12.2%; P = 0.36) or laparoscopic (3.3% vs 1.7%; P > 0.99) hepatic resection after propensity score matching. Incidence rate of surgical site infections was comparable between the short‐ and long‐term groups among patients undergoing open (13.5% vs 10.8%; P = 0.80) or laparoscopic (3.3% vs 1.7%; P > 0.99) hepatic resection. Conclusion: Giving short‐term prophylactic antibiotics might be sufficient in preventing postoperative infectious complications in patients undergoing open and laparoscopic hepatic resection. [ABSTRACT FROM AUTHOR]

Aim: Pancreaticobiliary maljunction (PBM) with or without congenital biliary dilatation (CBD) is a risk factor for biliary tract cancer. We investigated long‐term outcomes after biliary diversion operation with special reference to types of CBD. Methods: Subjects comprised 40 adult patients who underwent biliary diversion operation for PBM without biliary tract cancer. Group A comprised 20 patients with type Ia or Ic CBD, or non‐dilated bile ducts, while group B comprised 20 patients with type IV‐A CBD. The clinical findings and postoperative outcomes were compared between groups. Results: Of 40 patients, nine patients suffered from repeated cholangitis and eight of these nine patients suffered from hepatolithiasis after biliary diversion operation. Biliary tract cancer or pancreatic cancer was detected in four patients at 3 years and 2 months to 24 years after the operation. In three of these four patients, the serum concentration of carbohydrate antigen 19‐9 increased before detection of carcinoma. One patient died of hepatic failure due to repeated cholangitis. The proportions of patients with repeated cholangitis, hepatolithiasis, and re‐operation, and patients who died of biliary tract cancer, pancreatic cancer, or hepatic failure, were significantly higher in group B than in group A. The survival rate was significantly worse in group B than in group A. Conclusions: Careful long‐term follow‐up with measurement of serum tumor markers is necessary after biliary diversion operation for PBM, especially in patients with type IV‐A CBD or repeated cholangitis. This study showed that careful long‐term follow‐up with measurement of serum tumor markers is necessary after biliary diversion operation for PBM, especially in patients with type IV‐A CBD who were found to have significantly less favorable outcomes. [ABSTRACT FROM AUTHOR]

Background: Elevated oxidative stress is accepted to be the initial event in vitiligo leading to the final pathological regulation of immune systems known as autoimmune reaction, which destroys melanin‐forming cells, melanocytes. Recently, we reported an efficient topical use of PAPLAL, nanocolloid of platinum and palladium, having intense catalase‐like activity to vitiligo patients. In addition, we found that PAPLAL has dual effects on the AhR and Nrf‐2 pathways in keratinocytes, and suggested its contribution to the recovery of immune state in vitiligo. The precise mechanism developing autoimmune reaction in vitiligo, however, remains to be clarified. It is important to clarify what kinds of cells play an essential role in the development of vitiligo. Objective: To further understand the effective mechanisms of PAPLAL on immunity of skin, and to confirm a role of autoimmunity in vitiligo development, we studied the effect of PAPLAL on macrophage polarization and its activities which are recognized to play a pivotal role in immune and inflammatory reactions in many organs. Methods: Rat and human macrophages were cultured and stimulated in vitro with both LPS and IFN‐γ for M1 polarization and IL‐4 and IL‐13 for M2 polarization with or without PAPLAL. Expression of typical M1 and M2 markers was determined at mRNA and protein levels. Results: Simultaneous treatment with PAPLAL suppressed remarkably the production of M1 markers, iNOS, and TNF‐α; further, PAPLAL also suppressed M2 markers, mannose receptor (Man R), Chitinase 3‐like 3 (YM‐1), and iron regulatory protein‐1 (IRP‐1), at mRNA and protein levels, but less effectively compared to those of M1. PAPLAL, however, did not suppress phagocytic activity of M0, M1, and M2 cells. Conclusion: These results indicate that macrophages may be involved in the therapeutic potential of PAPAL by altering immunological environment disturbed in skin, with the delicate shift of the M1‐M2 polarization, but without affecting on phagocytic activity. The therapeutic potential of PAPAL in vitiligo could be mediated by regulating the immune homeostasis in disturbed skin. It shifts the inflammatory environment to the normal condition with the strong suppression of M1 and slight suppression of M2 macrophage polarization with no suppressive effect on their phagocytic activities. [ABSTRACT FROM AUTHOR]

Alveolar macrophages are key contributors to both the promotion and resolution of inflammation in the lung and are categorized into pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes. The change in M1/M2 balance has been reported in various pulmonary diseases and is a target for therapeutic intervention. The aim of this study was to assess the modulation of M1/M2 phenotype in alveolar macrophages by water-soluble carbon monoxide-releasing molecule-3 (CORM-3). Rat alveolar macrophages (AM) (NR8383) in culture were stimulated with LPS (5 ng/ml)/IFN-γ (10 U/ml) or IL-4 (10 ng/ml)/IL-13 (10 ng/ml) to induce M1 and M2 phenotypes, respectively. Expression of M1 phenotype markers, iNOS and TNF-α, and M2 phenotype markers, CD206 and Ym-1, was assessed by western blotting after 1, 3, 6, or 24 h in the absence or presence of CORM-3 (0.15 mM) treatment. Inactive CORM-3 (iCORM-3) was used as a control. Treatment of naïve (unstimulated) AM with CORM-3 promoted progression of the M2 phenotype as evidenced by the increased expression of CD206 (at 1 h; 1.8-fold) and Ym-1 (at 3 h; 1.9-fold), respectively. Surprisingly, CORM-3 treatment also upregulated the expression of iNOS protein as assessed 6 h following stimulation of AM with CORM-3 (2.6-fold). On the contrary, CORM-3 effectively reduced LPS/IFN-γ-induced expression of iNOS protein (0.6-fold); however, it had no effect on TNF-α expression. Finally, CORM-3 acutely (1-3 h) upregulated CD206 (1.4-fold) and Ym-1 (1.6-fold) levels in IL-4-/IL-13-treated (M2-stimulus) macrophages. These findings indicate that CORM-3 modulates macrophage M1 and M2 phenotypes in vitro with respect to continuous suppression of iNOS expression in M1-polarized macrophages and transient (early-phase) upregulation of CD206 and Ym-1 proteins in M2-polarized macrophages. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) develops in some patients who achieve sustained virological response (SVR) against hepatitis C virus (HCV) infection via anti-HCV therapy. To examine the pathogenesis of HCC development after HCV eradication, histopathological changes and clinical markers were evaluated in SVR patients. Methods: Of 654 SVR patients treated with interferon (IFN)-based therapies, 34 patients who had undergone liver biopsy before initiating IFN therapy and after SVR achievement were enrolled: 11 patients with HCC and 23 patients without HCC (male/female, 9/2 and 8/15, respectively: age, 58 ± 5 and 54 ± 11 years, respectively). We compared the clinical and histopathological factors between the two groups. Immunohistochemistry for Cytoglobin (CYGB) and α smooth muscle actin (α-SMA) was also performed. Results: At baseline, prior to initiating the IFN-based therapy, there were significant differences between the SVR-non-HCC and SVR-HCC groups in the male gender, HBc antibody positivity, prothrombin activity, and histological inflammatory grade. Histopathological evaluation, using the new Inuyama classification system, revealed an improvement in the inflammatory grade, from 2.1 ± 0.6 to 1.0 ± 0.6 (p < 0.0001), whereas the fibrosis stage remained unchanged, from 2.3 ± 0.9 to 2.0 ± 1.2 (p = 0.2749), during the 97 ± 72-month observation period in the SVR-HCC group. Both the grade and stage scores were significantly improved in the SVR-non-HCC group. The area of collagen deposition, evaluated using Sirius red staining, showed a marked decrease, from 18.6 ± 7.6% to 7.7 ± 4.6%, in the SVR-non-HCC group, with no change in the SVR-HCC group. CYGB- and α-SMA-positive hepatic stellate cells (HSCs), indicative of the HSC activated phenotype, remained in the fibrotic tissue of livers among patients in the SVR-HCC group. Conclusion: Stagnation of fibrosis regression is associated with a high risk for HCC after SVR. HSC activation may inhibit improvement in fibrosis after SVR and potentially contribute to hepatocarcinogenesis. [ABSTRACT FROM AUTHOR]

Purpose: To determine the recommended dose (RD) of gemcitabine (GEM) plus S-1 (GS) in curatively resected biliary tract cancer (BTC) patients without major hepatectomy.Methods: A standard 3 + 3 dose-escalation design was used with planned dose levels (mg/m2) of GEM (administered intravenously on days 1 and 8) and S-1 (administered orally twice daily on days 1-14, with a 1-week rest, every 3 weeks for up to 24 weeks) of 1000/80 (Level 2), 1000/65 (Level 1), 800/65 (Level - 1), and 800/50 (Level - 2).Results: Thirty-one patients (17 men and 14 women; median age, 70 years) were enrolled. Level 1 was chosen as the starting dose. Three of seven patients developed dose-limiting toxicities at Level 1 and the dose was de-escalated to Level - 1. Five of 12 patients developed Grade 4 neutropenia at Level - 1 and the dose was de-escalated to Level - 2. One patient developed Grade 4 neutropenia at Level - 2. Another patient was unable to receive the day 8 dose due to Grade 3 neutropenia at Level - 2. Level - 1 was confirmed as the maximum tolerated dose and Level - 2 the RD for this regimen. The 1- and 2-year recurrence-free survival rates were 77.0 and 54.0%, respectively. The recurrence-free survival rate of patients in the GS completion group was significantly higher than that of the GS discontinuation group.Conclusions: Level - 2 was confirmed as the RD (GEM 800 mg/m2 and S-1 50 mg/m2) for GS adjuvant chemotherapy in curatively resected BTC patients without major hepatectomy. [ABSTRACT FROM AUTHOR]

Purpose: The influence of allogenic blood transfusion on the postoperative outcomes of hepatocellular carcinoma (HCC) surgery remains controversial. This study aims to clarify the clinical impacts of perioperative allogenic blood transfusion on liver resection outcome in HCC patients. Methods: We analyzed data collected over 5 years for 642 patients who underwent hepatectomy for HCC at one of the five university hospitals. We investigated the impact of allogenic blood transfusion on postoperative outcome after surgery in all patients and in 74 matched pairs, using a propensity score. Results: Of the 642 patients, 198 (30.8%) received perioperative allogenic blood transfusion (AT group) and 444 (69.2%) did not (non-AT group). Overall survival was lower in the AT group than in the non-AT group in univariate ( P < 0.001) and multivariate analyses (risk ratio 1.521, P = 0.011). After matching the different distributions using propensity scores, perioperative blood transfusion was found to be a poor prognostic factor for HCC patients. Conclusions: In this multi-center study, perioperative blood transfusion was an independent factor for poor prognosis after curative surgery for primary HCC in the patient group and in pairs matched by propensity scores. [ABSTRACT FROM AUTHOR]

Purpose: To retrospectively investigate magnetic resonance (MR) imaging findings of occupational cholangiocarcinoma (oCC) occurring among workers in printing companies in Japan, compared to those of non-occupational cholangiocarcinoma (nCC), primary sclerosing cholangitis (PSC), and age-matched normal controls (NORs).Materials and Methods: Participants comprised 27 consecutive patients (oCC, n = 5; nCC, n = 8; PSC, n = 6; NOR, n = 8) who underwent MR imaging between May 2009 and October 2012. MR imaging was evaluated with respect to tumor characteristics, abnormal MR cholangiographic findings (PSC-like findings), bile duct stricture, and signal changes of the hepatic parenchyma.Results: Tumors were detected in all nCCs and four oCCs. Tumors displayed a mass-forming type in all nCCs and two oCCs, and an intraductal growth type in two oCCs. Abnormal cholangiographic findings were detected in all oCCs and PSCs, but not in any nCCs or NORs. All oCCs and seven nCCs showed biliary strictures longer than 1 cm; five PSCs showed biliary strictures shorter than 1 cm. Both intra- and extrahepatic biliary strictures were detected in three PSCs and two oCCs. Peripheral hepatic hyperintensity on T2-weighted imaging was detected in two nCCs, two PSCs, and two oCCs.Conclusion: These results indicated that MR imaging of oCC showed findings of both PSC and nCC. [ABSTRACT FROM AUTHOR]

Background and objectives: We determined the rates of initial lymph node metastasis following curative resection of mass-forming type-intrahepatic cholangiocarcinoma (ICC) in patients with and without hepatitis virus infection. Methods: We enrolled 87 patients between January 2000 and December 2013 with ICC without preoperative lymph node metastasis and without lymph node dissection. Patients included 32 who were seropositive for hepatitis B or C virus (virus group) and 55 who had no evidence of hepatitis virus infection (nonvirus group). Postsurgical outcomes and initial recurrence of the groups were compared, and we identified the risk factors for lymph node metastasis as initial recurrence. Results: Platelet counts and prothrombin activities were significantly lower in the virus group compared with those of the nonvirus group. The number of patients with chronic hepatitis or liver cirrhosis was significantly higher in the virus group compared with the nonvirus group as well as their respective rates of recurrence-free survival. One patient (3%) in the virus group and 14 patients (25%) in the nonvirus group had lymph node metastasis as initial recurrence ( p = 0.007). Multivariate analysis revealed that the absence of hepatitis virus infection as an independent risk factor ( p = 0.047). Conclusion: Hepatitis virus-associated mass-forming-type ICC confers a low risk of lymph node metastasis as initial postoperative recurrence. [ABSTRACT FROM AUTHOR]

Background: Focal nodular hyperplasia (FNH) is the second most common benign hepatic tumor and is very rarely complicated by hemorrhage or rupture. Although thought to be extremely rare, there have been several reports of hemorrhage caused by ruptured FNH. Herein, we report the case of a patient with ruptured FNH, who subsequently developed hemorrhage during follow-up. Case presentation: A 32-year-old man was admitted to our department for an asymptomatic hepatic tumor in segments 4 and 5 (S4/5), which measured 8 cm in diameter and observed to project from the liver. Imaging and pathologic examination of a biopsy specimen confirmed the diagnosis of FNH. Three years after the diagnosis, the patient was readmitted to our hospital because of sudden onset of upper abdominal pain. Dynamic abdominal computed tomography revealed ascites around the tumor with high-density areas that were considered to represent hematoma caused by ruptured FNH. Transcatheter arterial embolization (TAE) was performed to stop the hemorrhage. One month after TAE, S4/5 of the liver was resected; macroscopic findings revealed that a large part of the tumor was composed of necrotic tissue and hematoma. Pathological examination using hematoxylin-eosin staining and immunohistochemical examination indicated a final diagnosis of FNH rupture and hemorrhage. Conclusion: Although a well-established diagnosis of FNH usually requires no treatment or surveillance, careful examination remains necessary when the FNH is large and projects from the liver because of the possibility of rupture and hemorrhage. [ABSTRACT FROM AUTHOR]

An outbreak of cholangiocarcinoma in a printing company was reported in Japan, and these cases were regarded as an occupational disease (occupational cholangiocarcinoma). This study examined the expression status of programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) in occupational cholangiocarcinoma. Immunostaining of PD-1, PD-L1, CD3, CD8, and CD163 was performed using tissue sections of occupational cholangiocarcinoma (n = 10), and the results were compared with those of control cases consisting of intrahepatic (n = 23) and extrahepatic (n = 45) cholangiocarcinoma. Carcinoma cells expressed PD-L1 in all cases of occupational cholangiocarcinoma, whereas the detection of PD-L1 expression in cholangiocarcinoma cells was limited to a low number of cases (less than 10%) in the control subjects. In cases of occupational cholangiocarcinoma, occasional PD-L1 expression was also noted in precancerous/preinvasive lesions such as biliary intraepithelial neoplasia and intraductal papillary neoplasm of the bile duct. Additionally, tumor-associated macrophages and tumor-infiltrating T cells expressed PD-L1 and PD-1, respectively. The number of PD-L1-positive mononuclear cells, PD-1-positive lymphocytes, and CD8-positive lymphocytes infiltrating within the tumor was significantly higher in occupational cholangiocarcinoma compared with that in control cases. These results indicate that immune escape via the PD-1/PD-L1 axis may be occurring in occupational cholangiocarcinoma. [ABSTRACT FROM AUTHOR]

Background: Among young residents, there seems to be a decreasing desire to become surgeons, resulting in a decrease in the number of surgeons. There is concern regarding a shortage of hepatobiliary pancreatic (HBP) surgery residents in Japan. A questionnaire survey was designed to assess the work motivations of Japanese gastrointestinal (GI) and HBP surgeons. Methods: Questionnaires assessing seven domains related to motivation (aptitude, satisfaction/dissatisfaction, knowledge/skill, evaluation/approval, self‐management, community/expectation from other parties, and emotion) were sent to GI and HBP surgeons throughout Japan. Differences between HBP and GI surgeons were analyzed. Results: Responses were received from 27 institutions in Japan between May and August 2014. Mid‐career and senior HBP surgeons (11–20 years after graduation) working in university hospitals were significantly less satisfied with their work than GI surgeons (P = 0.036). Evaluation/approval factors were significantly lower in senior HBP surgeons than in GI surgeons 16–20 years after graduation (P = 0.048). Conclusions: The future satisfaction of young residents seeking to become HBP surgeons should be enhanced, providing an appealing workplace for young residents and preventing discontinuation by mid‐career and senior surgeons. Highlight Kaibori and colleagues revealed that hepatobiliary pancreatic surgeons have less work motivation than gastrointestinal surgeons, especially in the domains “satisfaction/dissatisfaction” and “evaluation/approval”. The future work motivation of young residents seeking to become hepatobiliary pancreatic surgeons should be enhanced, providing an appealing workplace and preventing discontinuation by mid‐career and senior surgeons. [ABSTRACT FROM AUTHOR]

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. Highlight In patients with occupational cholangiocarcinoma caused by exposure to 1,2‐dichloropropane, dichloromethane, or both, Kubo and colleagues showed that multicentric recurrence occurred not infrequently after resection of the cholangiocarcinoma because of the high carcinogenic potential of the bile duct. Aggressive treatment including resection for the multicentric recurrence appeared to be effective. [ABSTRACT FROM AUTHOR]

Background: An outbreak of cholangiocarcinoma has been reported among workers of an offset color proof‐printing department at a printing company in Japan. In this study, we compared the clinicopathological findings of this type of intrahepatic cholangiocarcinoma (occupational ICC) and non‐occupational ICC. Methods: The clinical records of 51 patients with perihilar‐type ICC who underwent liver resection, including five patients with occupational ICC were retrospectively reviewed. The clinicopathological features were compared. Results: In the occupational group, the patients were significantly younger (P < 0.01), while serum γ‐glutamyl transpeptidase activity and the proportions of patients with regional dilatation of the bile ducts without tumor‐induced obstruction were significantly higher (P = 0.041 and P < 0.01, respectively); the indocyanine green retention rate at 15 min was significantly lower (P = 0.020). On pathological examinations, precancerous or early cancerous lesions, such as biliary intraepithelial neoplasia and intraductal papillary neoplasm of the bile duct, were observed at various sites of the bile ducts in all occupational ICC patients; such lesions were observed in only six patients in the control group (P < 0.01). Conclusions: The clinicopathological findings including age, liver function test results, diagnostic imaging findings, and pathological findings differed between the occupational and control groups. Highlight Age, liver function test results, diagnostic imaging findings and pathological findings differed between occupational and non‐occupational intrahepatic cholangiocarcinoma. Hamano and colleagues suggest that these differences may be based on different carcinogenic processes between the conditions, and they stress the importance of regular health examinations for workers exposed to organic solvents. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to establish an efficient strategy for screening and surveillance for occupational cholangiocarcinoma. Methods: We evaluated the consecutive changes in laboratory findings during regular health examinations and in abdominal ultrasonography findings before the diagnosis of occupational cholangiocarcinoma in nine patients. The results of laboratory tests and abdominal ultrasonography at the time of diagnosis were also examined. Results: In all patients, the serum γ-glutamyl transpeptidase (γ-GTP) activity increased several years before the diagnosis of cholangiocarcinoma. The serum alanine aminotransferase (ALT) activity also increased several years before the diagnosis, following an increase in the serum aspartate aminotransferase (AST) activity in most patients. Abdominal ultrasonography before the diagnosis revealed regional dilatation of the bile ducts, which continued to enlarge. At the time of diagnosis, the γ-GTP, AST, and ALT activities were increased in nine, seven, and seven patients, respectively. The regional dilatation of bile ducts without tumor-induced stenosis, dilated bile ducts due to tumor-induced stenosis, space-occupying lesions, and/or lymph node swelling were observed. The serum concentrations of carbohydrate antigen 19-9 (CA 19-9) and/or carcinoembryonic antigen (CEA) were increased in all patients. Conclusions: Regular health examinations with a combination of ultrasonography and laboratory tests including the γ-GTP, AST, ALT, CA 19-9, and CEA levels are useful for screening and surveillance for occupational cholangiocarcinoma. [ABSTRACT FROM AUTHOR]

Aim Percutaneous radiofrequency ablation (P-RFA) therapy is a widely applied treatment for small hepatocellular carcinoma (HCC); however, local recurrence is a major issue of HCC located at the surface of the liver (surface HCC). The aim of this study was to compare the outcome of laparoscopic hepatic resection (LH) and P-RFA for surface HCC in case-control patient groups using the propensity score. Methods Between 2011 and 2013, 40 and 52 patients underwent LH and P-RFA for surface HCC (≤3 cm, 1-3 nodules). To correct the difference in clinicopathological factors between the two groups, propensity score matching was used at a 1:1 ratio, which resulted in a comparison of 27 patients/group. We compared outcomes between the two groups, with special reference to local recurrence. Results Clinicopathological variables were well balanced between the two groups. One patient in the LH group was converted to open surgery due to adhesion. The incidence of complications was 0% in the P-RFA group and 15% (four patients) in the LH group ( P = 0.11); however, none of these four patients in the LH group sustained severe complications. The duration of hospitalization following treatment was longer in the LH group than in the P-RFA group (12.6 vs 7.6 days, P < 0.01). The incidence of local recurrence was lower in the LH group (0%) than in the P-RFA group (eight patients [30%], P = 0.004). Conclusion LH is an effective treatment for surface HCC with regard to control of local recurrence. [ABSTRACT FROM AUTHOR]

Aim Hepatocellular carcinoma (HCC) develops in up to 5% of patients after the successful treatment of chronic hepatitis C virus (HCV) infection using interferon therapy. The aim of this study was to characterize miRNA expression in liver tissues from patients who achieved a sustained viral response (SVR). Methods Seventy-one patients with resected HCC were enrolled into the present study: 61 HCC from patients with continuously infected HCV (HCV-HCC) and 10 from patients who had achieved SVR (SVR-HCC). We also included non-tumor tissues (SVR-NT) from four patients with SVR-HCC, and liver tissue (SVR-CH) from four SVR patients without HCC. Total RNA was extracted from liver samples. The miRNA expression patterns were analyzed using microarrays. In addition, target gene expression was quantified after miRNA overexpression in HEK293 cells. Results We could discriminate between SVR-HCC and HCV-HCC with 75.36% accuracy using the expression pattern of six specific miRNA. The expression levels of 37 miRNA were significantly lower in HCV-HCC than in SVR-HCC, whereas the expression of 25 miRNA was significantly higher in HCV-HCC than SVR-HCC ( P < 1.0E-05). The expression of thrombospondin 1 was regulated in an opposing manner by miR-30a-3p in SVR-HCC and HCV-HCC. In non-tumor tissues, the expression pattern of seven miRNA could distinguish between SVR-CH and SVR-NT with 87.50% accuracy. Conclusion Comprehensive miRNA expression analyses could not only differentiate between SVR-HCC and HCV-HCC but also forecast hepatocarcinogenesis after achieving SVR. [ABSTRACT FROM AUTHOR]

Background: We aimed to identify the pathological characteristics of occupational cholangiocarcinoma. Methods: We examined the location and distribution of the carcinomas: atypical epithelium including biliary intraepithelial neoplasia (BilIN) and intraductal papillary neoplasm of the bile duct (IPNB); and chronic bile duct injuries in operative or autopsy liver specimens from 16 patients. We examined the detailed pathological findings and diagnostic imaging of three patients. Immunohistochemical analysis using primary antibodies against γH2AX and S100P was performed. Results: BilIN and chronic bile duct injury were observed in 16 patients, and IPNB or invasive IPNB was observed in 11 patients. BilIN, IPNB, and/or chronic bile duct injury were observed in almost all the large bile ducts. Regional dilatation of the bile ducts without tumor‐induced obstruction revealed such pathological changes. Highly positive results for the γH2AX and S100P markers were noted in invasive carcinoma, BilIN, and IPNB, whereas positive results for γH2AX and negative results for S100P were noted in non‐neoplastic biliary epithelium. Conclusions: The carcinogenic process of occupational cholangiocarcinoma comprised chronic bile duct injury and DNA damage in almost all the large bile ducts, along with induction of precancerous lesions and development of invasive carcinoma. Such pathological findings reflected radiological changes on diagnostic imaging. Highlight In patients with occupational cholangiocarcinoma, Kinoshita and colleagues report a carcinogenic process consisting of chronic bile duct injury with DNA damage that occured within almost all of the large bile ducts, the induction of pre‐ or early cancerous lesions such as BilIN and IPNB, and the development of invasive carcinoma. [ABSTRACT FROM AUTHOR]

Background: The lung is the most common site of extrahepatic metastasis from hepatocellular carcinoma (HCC). The aim of this study was to evaluate the significance and long-term outcomes of pulmonary metastasectomy for HCC, especially in patients with multiple nodules or repeated pulmonary recurrence. Methods: We retrospectively analyzed 19 patients who underwent pulmonary metastasectomy for HCC at our institution from 1993 to 2013. Results: No in-hospital mortality occurred. The 19 patients included 14 men. The median age was 61 (range 20-76) years. Eight patients (42 %) had single pulmonary metastatic lesions, whereas 4 (21 %) had >10 lesions. Median follow-up after pulmonary metastasectomy was 23.1 (6.3-230) months. Twelve patients died, and the cause of death was HCC progression in nine. The 1-, 3-, 5-, and 10-year overall survival rates after pulmonary metastasectomy were 89, 48, 48, and 21 %, respectively. Seven patients developed pulmonary recurrence after initial pulmonary metastasectomy. Five of the seven underwent repeat metastasectomy, with a median survival time of 65 months, and 2- and 3-year survival rates of 100 and 67 %, respectively. The 2- and 3-year survival rates in the four patients with >10 pulmonary nodules were 75 and 50 %, respectively. Conclusions: Surgical resection is a safe and effective treatment in selected patients with pulmonary metastasis from HCC, even in those with multiple nodules. Repeated locoregional therapy for lung recurrence might help to improve survival in these patients. [ABSTRACT FROM AUTHOR]

Background/Purpose: Laparoscopic hepatic resection (LH) for hepatocellular carcinoma (HCC) has gradually gained ground as a safe and minimally invasive treatment, although LH for cirrhotic patients remains challenging. Methods: Between January 2007 and August 2014, 28 and 57 patients with histologically proven cirrhosis (histological activity index, fibrosis score 4) underwent pure LH and open hepatic resection (OH; less than segmentectomy), respectively, for peripheral HCC ≤5 cm. To correct the difference in clinicopathological factors, including difficulty scores, between the two groups, propensity score matching was used at a 1:1 ratio, which resulted in a comparison of 20 patients per group. We compared the short- and long-term outcomes of LH and OH to investigate the efficacy of LH. Results: Clinicopathological variables, including difficulty scores, were well balanced between the two groups. The incidence of complications and mean intraoperative blood loss were lower in the LH group than the OH group (0 vs. 45% and 180 vs. 440 ml, p = 0.001 and 0.04, respectively). The 3-year disease-free survival rate was 42% in the LH group and 30% in the OH group (p = 0.533), whereas the 5-year overall survival rates were 46 and 60%, respectively (p = 0.606). Conclusions: LH is a safe and effective treatment option for cirrhotic patients with HCC in terms of intraoperative blood loss and morbidity. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Purpose: We evaluated the preoperative and postoperative characteristics and prognosis of super-elderly patients with hepatocellular carcinoma (HCC). Methods: Four hundred and thirty-one patients who underwent hepatic resection for HCC were classified into three groups according to their age at the time of surgery: super-elderly (≥80 years; n = 20), elderly (70-80 years; n = 172) and younger (<70 years; n = 239). We compared the clinical characteristics, preoperative and postoperative factors and prognosis among the groups to evaluate whether liver resection is appropriate for super-elderly patients. Results: The liver function was not significantly different among the groups. The proportion of patients with preoperative cardiovascular and respiratory disease and hypertension was higher in the super-elderly group compared to the other groups. The super-elderly group had shorter operations and reduced hemorrhage rates compared to the other groups. Postoperative cardiovascular complications and delirium were more frequently observed in the super-elderly group. The overall and tumor-free survival rates were not significantly different among the groups. Super-elderly patients had a lower rate of liver or HCC-related death and a higher rate of death due to other causes than the other groups. Conclusions: Super-elderly HCC patients who are appropriately evaluated and selected might have a favorable prognosis after undergoing hepatic resection. [ABSTRACT FROM AUTHOR]