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Aims: Lymph node metastases (LNM) are associated with lethal prognosis in intrahepatic cholangiocarcinoma (ICC). Lymphadenectomy is crucial for accurate staging and hopes of possible oncological treatment. However, the therapeutic implications and optimal extent of lymphadenectomy remain contentious. Methods: To clarify the prognostic value and optimal extent of lymphadenectomy, the therapeutic index (TI) for each lymph node was analyzed for 279 cases that had undergone lymphadenectomy in a multi‐institutional database. Tumor localization was divided into hilar lesions (n = 130), right peripheral lesions (n = 60), and left peripheral lesions (n = 89). In addition, the lymph node station was classified as Level 1 (LV1: hepatoduodenal ligament node), Level 2 (LV2: postpancreatic or common hepatic artery nodes), or Level 3 (LV3: gastrocardiac, left gastric artery, or celiac artery nodes). Results: Lymph node metastases were confirmed in 109 patients (39%). Five‐y survival rates were 45.3% for N0 disease, 27.1% for LV1‐LNM, 22.9% for LV2‐LNM, and 7.3% for LV3‐LNM (P < 0.001). LV3‐LNM were the most frequent and earliest recurrence outcome, including multisite recurrence, followed by LV2, LV1, and N0 disease. The 5‐year TI (5year‐TI) for lymphadenectomy was 7.2 for LV1, 5.5 for LV2, and 1.9 for LV3. Regarding tumor location, hilar lesions showed 5‐year TI >5.0 in LV1 and LV2, whereas bilateral peripheral lesions showed 5‐year TI > 5.0 in LV1. Conclusion: The implications and extent of lymphadenectomy for ICC appear to rely on tumor location. In the peripheral type, the benefit of lymphadenectomy would be limited and dissection beyond LV1 should be avoided, while in the hilar type, lymphadenectomy up to LV2 could be recommended. [ABSTRACT FROM AUTHOR]

Background: Lymph node metastasis (LNM) has been established as a critical risk factor for prognosis in intrahepatic cholangiocarcinoma (ICC). The clinical implications of lymph node dissection (LND) have been debated. This study aimed to clarify the prognostic impact of LND by multicenter retrospective analysis. Methods: A total of 310 ICC patients who had undergone curative resection between 2000 and 2016 were retrospectively analyzed. The prognostic impact of LND was estimated under an inverse probability of treatment weighting (IPTW) approach using propensity scores. Results: LND was performed for 224 patients (72%), with LNM pathologically confirmed in 90 patients (40%). Prognosis was poorer for patients with LNM (median survival, 16.9 months) than for those without (57.2 months; P <.0001). One‐, 3‐, and 5‐year overall survival rates (OS) were comparable among LND+ (81.6%, 48.0%, and 37.5%, respectively) and LND– groups (81.6%, 55.4%, and 44.6%, respectively). However, advanced tumor, as characterized by larger tumor, multinodular lesions, and serosal invasion, was significantly more frequent in the LND+ group than in the LND– group. After IPTW adjusting for imbalances, 1‐, 3‐, and 5‐year OS were better in the LND+ group (83.5%, 52.2%, and 42.8%, respectively) than in the LND– group (71.9%, 32.4%, and 23.4%, respectively; P =.046). LND thus showed significant prognostic impact (hazard ratio = 0.58, 95%CI = |0.39|–|0.84|, P =.005), especially in hilar ICC. However, peripheral ICC displayed no therapeutic benefit from LND. Conclusions: LND could have a significant role to play in improving oncologic outcomes. Therapeutic LND should be implemented on the basis of tumor location and tumor advancement. [ABSTRACT FROM AUTHOR]

Bochdalek hernia is a congenital diaphragmatic hernia (DH). Herein, we report a case of adult Bochdalek hernia following living donor hepatectomy repaired by thoracoscopy‐assisted surgery. A 36‐year‐old man underwent living donor left hepatectomy. Four months later, the patient presented with acute epigastric pain. Computed tomography found the left‐sided DH in which the stomach was incarcerated into the pleural cavity without ischemic changes. As endoscopic intervention was unsuccessful, the herniated stomach was repositioned by thoracoscopy‐assisted surgery. The 3‐cm hernia orifice was found to have a smooth edge with no hernia sac, suggesting Bochdalek hernia, and the defect was primarily closed. The patient was followed up for 20 months without hernia recurrence. This is the first presentation of a case of Bochdalek hernia following donor hepatectomy. In cases of early detected DH, primary repair via a transthoracic approach with thoracoscopy‐assisted surgery is safe and feasible. [ABSTRACT FROM AUTHOR]

Objective: The usefulness of the modified Glasgow prognostic score (GPS) as a prognostic tool remains unclear for patients undergoing curative surgery for intrahepatic cholangiocarcinoma (ICC). Therefore, this study investigated the prognostic usefulness of the GPS for patients who underwent ICC surgery. Method: All ICC patients who had a curative-intent hepatectomy at 17 institutions between 2000 and 2016 were included. The correlation was assessed between the preoperative GPS and the baseline characteristics of the patients, histopathological parameters, surgical parameters, and the postresection overall survival (OS). Result: There were 273 patients who met the eligibility criteria between the years 2000 and 2016. The postoperative OS rates at 1, 3, and 5 years were 83.8%, 56.3%, and 41.5%, respectively (median OS, 47.7 months). A multivariate analysis revealed the factors that were associated with a worse OS, which included an increased GPS (hazard ratio = 1.62; 95% confidence interval [CI]: 1.01–2.53; P = 0.03), an elevated carcinoembryonic antigen level (hazard ratio = 1.60; 95% CI: 1.06–2.41; P = 0.02), an elevated carbohydrate antigen 19–9 level (hazard ratio = 1.55; 95% CI: 1.05–2.30; P = 0.03), undifferentiated carcinoma (hazard ratio = 2.41; 95% CI: 1.56–3.67; P < 0.01), and positive metastasis to the lymph nodes (hazard ratio = 2.54; 95% CI: 1.76–3.67; P < 0.01). In ICC patients after a hepatectomy, an elevated GPS was associated with poorer OS, even if the tumour factors that affected GPS were eliminated by propensity-score matching. Conclusion: Preoperative GPS can be useful to predict the postoperative outcomes of ICC patients. Therefore, this relatively simple and inexpensive scoring system can be utilized to further refine patient stratification as well as to predict survival. [ABSTRACT FROM AUTHOR]

Endoscopic ultrasonography (EUS)‐guided ethanol injection was recently proposed for treatment of patients with small pancreatic neuroendocrine tumors (p‐NET); however, tips on how to carry out safe and effective procedures are unclear. We launched a pilot study for scheduled early EUS‐guided ethanol reinjection for small p‐NET. Major eligibility criteria were presence of pathologically diagnosed grade (G) 1 or G2, tumor size ≤2 cm and being a poor or rejected candidate for surgery. For the treatment, we used a 25‐gauge needle and pure ethanol. Contrast‐enhanced computed tomography (CE‐CT) was carried out on postoperative day 3, and if enhanced areas of the tumor were still apparent, an additional session was scheduled during the same hospitalization period. Primary endpoint was complete ablation rate at 1 month after treatment, and secondary endpoint was procedure‐related adverse events. A total of five patients were treated. Median size of the tumor was 10 (range: 7–14) mm. Of the five patients, three underwent an additional session. Median volume of ethanol injection per session was 0.8 (range: 0.3–1.0) mL, and the total was 1.0 (0.9–1.8) mL. Complete ablation was achieved in four of the five tumors (80%) with no adverse events. During 1 year of follow up, none of the patients reported any procedure‐related adverse events, and no recurrence of tumor. Scheduled early EUS‐guided ethanol reinjection appears to be safe and effective for treating small p‐NET (UMIN number: 000018834). [ABSTRACT FROM AUTHOR]

Background and Aim: Although sporadic non‐ampullary duodenal adenoma is speculated to be precancerous lesion, the relationship between adenoma and carcinoma remains unclear due to their rarity. Previous studies on sporadic non‐ampullary duodenal epithelial neoplasm (SNADEN) have mainly targeted superficial tumors, like adenoma and early carcinoma. The clinicopathological features, including those of advanced carcinoma, remain poorly investigated. We assessed the clinicopathological features of SNADEN, including advanced carcinoma, focusing on tumor location. Methods: We retrospectively collected the data of 410 patients who had been clinically and pathologically diagnosed with SNADEN at 11 institutions in Japan between June 2002 and March 2014. Results: The SNADEN was mucosal neoplasia and invasive carcinoma in 321 (78.3%) and 89 (21.7%) patients, respectively. The proportion of invasive carcinomas in SNADEN was significantly higher on the oral side of the papilla of Vater (oral‐Vater) than on the anal side (anal‐Vater) (27.9% vs 14.4%, P < 0.001). Undifferentiated‐type carcinoma was significantly more frequent with oral‐Vater than anal‐Vater (38.7% vs 14.8%, P = 0.026). The recurrence rate of surgically R0 resected locally advanced carcinomas was significantly higher with oral‐Vater than anal‐Vater (46.4% vs 8.3%, P = 0.021). Furthermore, the relapse‐free survival with oral‐Vater was significantly shorter than with anal‐Vater (hazard ratio: 2.35; 95% confidence interval: 1.09–5.50; P = 0.028). Conclusions: The clinicopathological features of SNADEN on oral‐Vater were different from those on anal‐Vater. SNADEN on oral‐Vater was more likely to be invasive carcinomas and might behave more aggressively due to biologically higher malignancy than that on anal‐Vater. [ABSTRACT FROM AUTHOR]

Background: Immune-nutritional status has been recently reported as a prognostic factor in hepatocellular carcinoma (HCC). The controlling nutritional status (CONUT) score has been established as a useful tool to evaluate immune-nutritional status. This study aimed to investigate the efficacy of the CONUT score as a prognostic factor in patients undergoing hepatectomy for HCC. Methods: A total of 295 patients who underwent curative hepatectomy for HCC between January 2007 and December 2014 were retrospectively analyzed. Patients were divided into two groups according to the CONUT score. The impact of the CONUT score on clinicopathological, surgical, and long-term outcomes was evaluated. Subsequently, the impact of prognostic factors, including the CONUT score, associated with outcomes was assessed using multivariate analyses. Results: Of 295 patients, 118 (40%) belonged to the high CONUT group (CONUT score ≥ 3). The high CONUT group had a significantly lower 5-year recurrence-free survival rate than the low CONUT group (27.9 vs. 41.4%, p = 0.011) and a significantly lower 5-year overall survival rate (61.9 vs. 74.9%, p = 0.006). In multivariate analyses of prognostic factors, the CONUT score was an independent predictor of recurrence-free survival (hazard ratio = 1.64, p = 0.006) and overall survival (hazard ratio = 2.50, p = 0.001). Conclusions: The CONUT score is a valuable preoperative predictor of survival in patients undergoing hepatectomy for HCC. [ABSTRACT FROM AUTHOR]

Background Surgical indications for liver hemangioma remain unclear. Methods Of 510 patients undergoing surgical resection for liver hemangioma in 118 Japanese centers between 1998 and 2012, abdominal symptoms, diagnostic accuracy, and surgical outcomes were analyzed to propose size-based surgical indications. Patients were classified into four groups based on tumor size: Group A ≤5 cm ( n = 122, 24%), Group B 5-10 cm ( n = 164, 32%), Group C 10-15 cm ( n = 124, 24%), and Group D >15 cm ( n = 100, 20%). Results Hemangiomas in Group A were most frequently diagnosed as malignant tumors (43.5%) due to the absence of typical imaging findings and with highest incidence of positive HBV (15.7%). Diagnostic accuracy was 98.4% in Groups B to D. Liver failure after hepatectomy was higher in Group D than in Groups A to C (3.0% vs. 0.5%, P = 0.02). Only one operative death was observed (0.2%) in Group D. Conclusions In patients with ≤5 cm hemangioma, surgical resection can be indicated when a malignant tumor cannot be ruled out. However, surgery for 5-10 cm asymptomatic hemangiomas should be limited. Experienced hepatic surgeons should conduct hepatectomy for tumors >15 cm to avoid serious morbidity or mortality. [ABSTRACT FROM AUTHOR]

Background and Aim Pathological grading is important in defining the therapeutic strategy in pancreatic neuroendocrine neoplasm (PNEN) but is difficult for unresectable cases. Endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) is useful in the diagnosis of PNEN, but its usefulness for pathological grading is not well established. No studies have examined the diagnostic ability of dynamic computed tomography (CT) for pathological grading of PNEN. We investigated the usefulness of EUS-FNA and dynamic CT in the diagnosis and pathological grading of PNEN. Methods In this retrospective study, 39 PNEN patients finally diagnosed via EUS-FNA and/or surgical resection underwent dynamic CT. Pathological samples were diagnosed based on WHO2010; staging was based on the European Neuroendocrine Tumor Society classification. The proportion of the quantification value in the tumor to the pancreatic parenchyma in arterial phase was defined as the CT ratio. Immunohistochemical staining with CD31 was performed to evaluate microvessel density (MVD). We evaluated the relationship between pathological grade, CT ratio, and MVD. Results By using EUS-FNA, 35 of 39 (90%) cases were diagnosed as PNEN. As for pathological grade, 15 of 35 (43%) cases could be identified correctly. CT ratio could predict pathological Grade 3 disease. The sensitivity, specificity, and diagnostic accuracy were 100%, 94%, and 95%. MVD was significantly correlated with CT ratio ( r = 0.83, P < 0.0001) and pathological grade ( P = 0.0074). Conclusions Computed tomography ratio has a relationship with pathological grade in PNEN, which would help decide therapeutic strategy in unresectable cases and cases in which pathological grading is difficult. [ABSTRACT FROM AUTHOR]

Intrahepatic arterioportal fistula (IAPF) is a rare cause of portal hypertension that is often difficult to treat with interventional radiology or surgery. Liver transplantation for IAPF is extremely rare. We report a case of bilateral diffuse IAPF with severe portal hypertension requiring deceased donor liver transplantation (DDLT). A 51-year-old woman with no past medical history was admitted to another hospital complaining of abdominal distension and marasmus. A computed tomography scan and digital subtraction angiography indicated a massive pleural effusion, ascites, and a very large IAPF. Several attempts of interventional embolization of the feeding artery failed to ameliorate arterioportal shunt flow. As ruptures of the esophageal varices became more frequent, hepatic encephalopathy worsened. After repeated, uncontrollable attacks of hepatic coma, the patient was referred to our facility for further treatment. Surgical approaches to IAPF other than liver transplantation were challenging because of diffuse collateralization; therefore, we placed the patient on the national waiting list for DDLT. Although her Model for End-Stage Liver Disease score was relatively low, she received a DDLT 2 months after the waiting period. The postoperative course was uneventful, and the patient was discharged 44 days after her transplant. Liver transplantation may be a valid treatment option for uncontrollable IAPF with severe portal hypertension. [ABSTRACT FROM AUTHOR]

A combination of hepatitis B immunoglobulin ( HBIG) and nucleoside/nucleotide analogs ( NUC) is the current standard of care for controlling hepatitis B recurrence after orthotopic liver transplantation ( OLT). However, long-term HBIG administration is associated with several unresolved issues, including limited availability and extremely high cost, and thus several protocols for treatment with low-dose HBIG combined with NUC or HBIG-free regimens have been developed. This article reviews recent advances in post- OLT hepatitis B virus ( HBV) control and future methodological directions. New NUC such as entecavir, tenofovir or lamivudine plus adefovir dipivoxil combinations induce a very low frequency of viral resistance. The withdrawal of HBIG after several months of OLT under new NUC continuation also has permissible effects. Even after HBV reactivation, NUC can usually achieve viral control when viral markers are strictly followed up. Another approach is to induce self-producing anti- HBV antibodies via vaccination with a hepatitis B surface antigen vaccine. However, HBV vaccination is not sufficiently effective in patients to treat liver cirrhosis type B after OLT because immune tolerance to the virus has already continued for several decades. Trials of its safety and cost-effectiveness are required. This review advocates a safe and economical approach to controlling post- OLT HBV recurrence. [ABSTRACT FROM AUTHOR]

Background and Aim There have been few reports on the success rate of balloon dilation and stent deployment using endoscopic retrograde cholangiopancreatography by double-balloon enteroscopy ( DBE-ERCP) or on the follow-up period after stent removal in patients with a reconstructed digestive tract and stenosis of choledochojejunal anastomosis. The present study was designed to evaluate the usefulness of DBE-ERCP in patients with a reconstructed digestive tract and stenosis of choledochojejunal anastomosis. Methods Forty-four patients with stenosis of choledochojejunal anastomosis underwent DBE-ERCP at Okayama University Hospital between April 2008 and January 2012 (107 procedures). Rates of reaching choledochojejunal anastomosis, stent deployment, and restenosis after stent removal were retrospectively evaluated. Results Insertion of DBE into the choledochojejunal anastomotic site succeeded in 38 of 44 patients (86.4%), and anastomotic dilation and stent deployment succeeded in 36 of 44 patients (81.8%). In 32 of 44 patients (72.7%), their anastomotic stenoses were improved, and they achieved stent removal. After stent removal, restenosis of choledochojejunal anastomosis was detected in seven of 32 patients; however, the resolution of restenosis was achieved in all seven of those patients. Conclusion Dilation of choledochojejunal anastomosis combined with stent deployment using DBE-ERCP seems to be a viable first-line treatment for patients with stenosis of choledochojejunal anastomosis. [ABSTRACT FROM AUTHOR]

Aim Alcoholic liver cirrhosis ( ALC) is an established indication for liver transplantation ( LT). Although the importance of preoperative abstinence is accepted, the optimal period of pretransplant abstinence is unclear. Our previous report in a Japanese cohort revealed a significant negative impact of recidivism on patient survival but failed to show significance of the length of pretransplant abstinence. The aim of this study was to evaluate the optimal period of pretransplant abstinence. Methods Subjects underwent LT for ALC ( n = 195: 187 living donor liver transplantations, five deceased donor liver transplantations and three domino LT) in Japan from November 1997 to December 2011. Risk factors and the impact on outcome of alcohol relapse were analyzed in 140 patients, after excluding 26 patients with in-hospital mortality and 29 patients without information about alcohol relapse. Results The incidence of alcohol consumption after LT was 22.9% (32/140). The relapse time was within 18 months after LT in 24 patients, after 18 months in two patients and unknown in six patients. Alcohol-related damage occurred in 18 of the 24 patients with recidivism within 18 months. The patient survival rate of patients with harmful relapse was significantly lower than that of abstinent patients and patients with non-harmful relapse ( P = 0.019). Preoperative abstinence shorter than 18 months was a significant indicator of the risk of harmful relapse ( P = 0.009). High-risk alcohol relapse scores had no impact on the incidence. Conclusion Preoperative abstinence was an important predictor of post-transplant harmful relapse leading to inferior outcomes. [ABSTRACT FROM AUTHOR]

Background and Aim The reduced expression in immortalized cells REIC/the dickkopf 3 ( Dkk-3) gene, tumor suppressor gene, is downregulated in various malignant tumors. In a prostate cancer study, an adenovirus vector carrying the REIC/ Dkk-3 gene ( Ad-REIC) induces apoptosis. In the current study, we examined the effects of REIC/ Dkk-3 gene therapy in pancreatic cancer. Methods REIC/ Dkk-3 expression was assessed by immunoblotting and immunohistochemistry in the pancreatic cancer cell lines ( ASPC1, MIAPaCa2, Panc1, BxPC3, SUIT-2, KLM1, and T3M4) and pancreatic cancer tissues. The Ad-REIC agent was used to investigate the apoptotic effect in vitro and antitumor effects in vivo. We also assessed the therapeutic effects of Ad-REIC therapy with gemcitabine. Results The REIC/ Dkk-3 expression was lost in the pancreatic cancer cell lines and decreased in pancreatic cancer tissues. Ad-REIC induced apoptosis and inhibited cell growth in the ASPC1 and MIAPaCa2 lines in vitro, and Ad-REIC inhibited tumor growth in the mouse xenograft model using ASPC1 cells. The antitumor effect was further enhanced in combination with gemcitabine. This synergistic effect may be caused by the suppression of autophagy via the enhancement of mammalian target of rapamycin signaling. Conclusions Ad-REIC induces apoptosis and inhibits tumor growth in pancreatic cancer cell lines. REIC/ Dkk-3 gene therapy is an attractive therapeutic tool for pancreatic cancer. [ABSTRACT FROM AUTHOR]

Establishment of a preferential liver allocation rule for simultaneous liver and kidney transplantation ( SLK) and revisions of laws regarding organ transplants from deceased donors have paved the way for SLK in Japan. Very few cases of SLK have been attempted in Japan, and no such recipients have survived for longer than 40 days. The present report describes a case of a 50-year-old woman who had undergone living donor liver transplantation at the age of 38 years for management of post-partum liver failure. After the first transplant surgery, she developed hepatic vein stenosis and severe hypersplenism requiring splenectomy. She was then initiated on hemodialysis ( HD) due to the deterioration of renal function after insertion of a hepatic vein stent. She was listed as a candidate for SLK in 2011 because she required frequent plasma exchange for hepatic coma. When her Model for End-stage Liver Disease score reached 46, the new liver was donated 46 days after registration. The reduced trisegment liver and the kidney grafts were simultaneously transplanted under veno-venous bypass and intraoperative HD. The hepatic artery was reconstructed prior to portal reconstruction in order to shorten anhepatic time. Although she developed subcapsular bleeding caused by hepatic contusion on the next day, subsequent hemostasis was obtained by transcatheter embolization. Thereafter, her recovery was uneventful, except for mild rejection and renal tubular acidosis of the kidney graft. This case highlights the need to establish Japanese criteria for SLK. [ABSTRACT FROM AUTHOR]

We present a case in which combination chemotherapy was used to successfully treat hepatocellular carcinoma ( HCC) with rapid progression of lymph node ( LN) metastases after liver resection. In addition, epithelial to mesenchymal transition ( EMT) markers were examined immunohistochemically. A 43-year-old man who had been diagnosed with HCC showed an enlarged LN near the hepatic artery proper. After extended left lobectomy with lymphadenectomy in the hepatoduodenal ligament, he experienced rapid progression of metastases to the para-aortic and mediastinal LN. Partial remission was achieved after induction and maintenance of combination chemotherapy using etoposide, carboplatin, epirubicin and 5-fluorouracil. As a consequence of this treatment, the patient survived 10 months. Immunohistochemical studies demonstrated that HCC cells in the metastatic LN showed low expression of E-cadherin and high expression of N-cadherin and vimentin, indicating EMT. Combination chemotherapy may prove effective for patients with HCC accompanied by LN metastases that show features of EMT. [ABSTRACT FROM AUTHOR]

Background & Aim: Runt‐related transcription factor 3 (RUNX3) is a tumor suppressor gene that is expressed in gastric and other cancers including pancreatic cancer. However, the precise function of RUNX3 in pancreatic cancer has not been fully elucidated. In this study, we aimed to determine the effect of decreased RUNX3 expression in pancreatic cancer. Methods: This study included 36 patients with primary pancreatic cancer, who had undergone pancreaticoduodenectomy. All patients were treated with 1000 mg/m2 gemcitabine after the surgery. The pancreatic cancer cell lines PANC‐1, MIAPaCa‐2, BxPC‐3, SUIT‐2, and KLM‐1 were used for immunoblotting analysis of RUNX3 and multidrug resistance protein (MRP) expressions. Ectopic RUNX3 expression was achieved by cDNA transfection of the cells, and small interfering RNA (siRNA) against RUNX3 was used to knock down endogenous RUNX3. Cell growth in the presence of gemcitabine was assessed using the MTT assay. Results: Patients with RUNX3‐positive and RUNX3‐negative pancreatic cancer had a median survival of 1006 and 643 days, respectively. Exogenous RUNX3 expression reduced the expression of MRP1, MRP2, and MRP5 in endogenous RUNX3‐negative cells, whereas RUNX3 siRNA increased the expressions of these genes in endogenous RUNX3‐positive cells. Exogenous RUNX3 expression decreased gemcitabine IC50 in RUNX3‐negative cells. Conclusion: Loss of RUNX3 expression contributes to gemcitabine resistance by inducing MRP expression, thereby resulting in poor patient survival. Highlights: We categorized pancreatic cancer into 2 groups by RUNX3 expression.We defined the staining grade as low or high by using 30% staining area as cutoff.The prognosis was significantly poor in RUNX3‐negative subjects.RUNX3 protein expression reduced the expression of multidrug‐resistant proteins.RUNX3 expression increased gemcitabine sensitivity in pancreatic cancer cells. [ABSTRACT FROM AUTHOR]

Background: Surgical site infections (SSIs), particularly organ/space SSIs, remain a common cause of major morbidity after hepatectomy for hepatocellular carcinoma (HCC). Methods: Risk factors for SSIs were analyzed in 359 patients who underwent hepatectomy for HCC between 2001 and 2010. The causative bacteria, management, outcome, and characteristics of organ/space SSIs were investigated. Results: Anatomic hepatectomy was performed for 296 patients (82.5%), and repeat hepatectomy was carried out for 59 patients (16.4%). SSIs developed in 52 patients (14.5%; incisional, 24 cases; organ/space, 31 cases [3 patients showed both incisional and organ/space SSIs]). No in-hospital mortality related to incisional or organ/space SSIs was encountered. Independent risk factors for SSIs were repeat hepatectomy and operative time ≥280 min. Independent risk factors for organ/space SSIs were repeat hepatectomy and bile leakage. Methicillin-resistant Staphylococcus aureus was detected more frequently in organ/space SSIs after repeat hepatectomy than after initial hepatectomy. Conclusions: Repeat hepatectomy and bile leakage represent independent risk factors for organ/space SSIs after hepatectomy for HCC. Establishing treatment strategies is important for preventing postoperative bile leakage and reducing the high rate of organ/space SSIs after repeat hepatectomy. [ABSTRACT FROM AUTHOR]

Background: The discovery of practical biomarkers is important to realize personalized medicine for patients with malignant neoplasias, including colorectal cancer (CRC). Purpose: The aim of this study was to determine reliable prognostic biomarkers by the analysis of patients with resectable colorectal liver metastases (CRLM). Methods: Genomic DNA was obtained from the CRLM tissues of a cohort of 126 patients with CRLM with curative hepatic resection. The KRAS/ BRAF mutation spectrum and microsatellite instability (MSI) status were successfully analyzed in 100 of the 126 CRLM tissues and these findings were examined in relation to the patients' clinical outcomes. Results: The cohort of 100 CRLM patients consisted of 46 with synchronous and 54 with metachronous liver metastasis. Overall survival and disease-free survival at 5 years were 57.4 and 24.9 %, respectively. MSI analysis revealed that none of the 100 CRLM specimens showed any evidence of MSI. By KRAS/BRAF mutation analysis, the analyzed CRLM patients were divided into 3 groups; KRAS-mutant ( KRAS-Mt; n = 27), BRAF-mutant ( BRAF-Mt; n = 3), and wild-types of both genes (Wild-type; n = 70). In the survival analysis, both KRAS-Mt and BRAF-Mt patients showed significantly poorer prognoses compared with Wild-type patients. Furthermore, although the population with the BRAF mutation was small, this mutation had a significant negative impact on disease-free survival. Conclusions: In this study, all tumors in the cohort of CRLM patients were non-MSI tumors, suggesting MSI cancer in primary CRC would rarely reveal metastatic potential. KRAS and BRAF mutations are suggested to be poor prognostic factors in CRLM. Genetic information has an essential role as a prognostic marker and could contribute to the decisions on treatment strategy for CRLM. [ABSTRACT FROM AUTHOR]

Loss or decreased expression of runt-related transcription factor 3 (RUNX3), a tumor suppressor gene involved in gastric and other cancers, has been frequently observed in hepatocellular carcinoma (HCC). The objective of this study was to identify the regulatory mechanism of the epithelial-mesenchymal transition (EMT) by RUNX3 in HCC. Human HCC cell lines, Hep3B, Huh7, HLF and SK-Hep1, were divided into low- and high-EMT lines, based on their expression of TWIST1 and SNAI2, and were used in this in vitro study. Ectopic RUNX3 expression had an anti-EMT effect in low-EMT HCC cell lines characterized by increased E-cadherin expression and decreased N-cadherin and vimentin expression. RUNX3 expression has previously been reported to reduce jagged-1 (JAG1) expression; therefore, JAG1 ligand peptide was used to reinduce EMT in RUNX3-expressing low-EMT HCC cells. Immunohistochemical analyses were performed for RUNX3, E-cadherin, N-cadherin and TWIST1 in 33 human HCC tissues, also divided into low- and high-EMT HCC, based on TWIST1 expression. E-cadherin expression was correlated positively and N-cadherin expression was correlated negatively with RUNX3 expression in low-EMT HCC tissues. Correlations between EMT markers and RUNX3 mRNA expression were analyzed using Oncomine datasets. Similarly, mRNA expression of E-cadherin was also significantly correlated with that of RUNX3 in low-EMT HCC, while mRNA expression of JAG1 was negatively correlated with that of RUNX3. These results suggest a novel mechanism by which loss or decreased expression of RUNX3 induces EMT via induction of JAG1 expression in low-EMT HCC. [ABSTRACT FROM AUTHOR]

The small diameter of the hepatic artery is one of the complexities of living donor liver transplantation ( LDLT). We analyzed whether the direct suture technique using surgical loupes can simplify the operative process for LDLT compared with fixed microscopic reconstruction. We applied the direct technique to rationalize the operative process and abolished routine microsurgery from 2004. Two hundred and nine LDLT with a postoperative period over 34 months were carried out from 1996 to 2008. The patients were divided into two groups: the micro group (children: 20, adults: 72) and the non-micro group (children: 12, adults: 97). Running anastomosis was undertaken in the non-micro group. The anastomotic size of the children was significantly smaller than that of the adults, but larger than 2 mm (2.38 ± 0.4 vs. 2.7 ± 0.47 mm, p = 0.0005). By appropriate choice of the proximal artery, direct anastomosis is possible even in children. Early complications occurred in seven cases in the micro group, but none occurred in the non-micro group (p < 0.05). Significant reductions were observed in operation time (p < 0.0001), blood loss (p < 0.05), and hospital stay (p < 0.01) in the non-micro group. Non-microscopic anastomosis is useful for the rationalization of LDLT. [ABSTRACT FROM AUTHOR]

Peritoneovenous shunt (PVS) is accepted as a treatment for refractory ascites due to liver cirrhosis. Infection is a well-known complication of shunting. However, the effects of PVS in terms of complications for renal disease are unclear. We encountered a case involving a 52-year-old man with alcoholic liver cirrhosis and complications of nephrotic syndrome that were worsened by PVS. He received PVS for refractory ascites due to alcoholic liver cirrhosis before coming to our hospital for evaluation for liver transplantation. Nephrotic syndrome was then identified due to cirrhosis-related membranoproliferative glomerulonephritis (MPGN). Prednisolone was administrated at 60 mg/day for MPGN. On day 5, he showed grade IV hepatic encephalopathy (West Haven criteria). Tapering prednisolone and intestinal cleansing with lactulose treatment improved hepatic encephalopathy, but hyperammonemia persisted and the PVS was removed. After shunt removal, urinary protein levels decreased from 4-6 g/day to 0.3-0.5 g/day and ammonia levels decreased. PVS may increase the excretion of urinary protein and increase ammonia levels in patients with complications of glomerulonephritis. [ABSTRACT FROM AUTHOR]

Background/purpose: Malnutrition and metabolic disorder of patients undergoing living donor liver transplantation (LDLT) can affect post-transplant prognosis. The aim of this study was to establish whether perioperative usage of branched-chain amino-acid (BCAA)-enriched nutrients improve metabolic abnormalities of patients undergoing LDLT. Methods: We designed a randomized pilot study (UMIN registration number; 000004323). Twenty-five consecutive adult elective LDLT recipients were enroled and divided into two groups: the BCAA group (BCAA-enriched nutrients, n = 12) and the control group (standard diet, n = 13). Metabolic and nutritional parameters, including BCAA-to-tyrosine ratio (BTR), retinol binding protein (RBP), and prealbumin were regularly measured from 1 week before to 4 weeks after LDLT. Non-protein respiratory quotient (npRQ) was measured before and 4 weeks after LDLT. Results: BTR and RBP improved considerably in the BCAA group compared with the controls. npRQ significantly increased from 1 week before LDLT to 4 weeks after LDLT in the BCAA group (0.77 ± 0.05 to 0.84 ± 0.06, P = 0.002), but not in the control group (0.78 ± 0.04 to 0.81 ± 0.05). Conclusions: Supplementation with BCAA-enriched nutrients might improve persistent nutritional and metabolic disorders associated with end-stage liver disease in the early post-transplant period, and consequently shorten the post-transplant catabolic phase after LDLT. A larger multicenter trial is needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Hepatoblastoma is a rare malignant tumor of the liver in children. Intensive combination chemotherapy has increased the number of surgically resectable cases and improved prognosis markedly. However, unresectable cases and cases with residual metastasis, including lung metastases, have a poor prognosis. In these refractory cases, treatment strategy has not been established. On the other hand, living liver transplantation has been shown to be effective in cases of advanced hepatoblastoma, but its effectiveness in cases with residual distant metastases after chemotherapy remains unclear. We report one successful case of advanced unresectable hepatoblastoma with multiple lung metastases. Intensive chemotherapy consisting of high-dose chemotherapy with autologous hematopoietic stem cell transplantation was not effective. We performed living liver transplantation after surgical resection of residual lung metastases, which were histologically viable. After liver transplantation, the level of tumor marker decreased gradually. The patient experienced no severe complications. This case suggested that living liver transplantation could be effective in cases of advanced refractory hepatoblastoma after control of distant metastases. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to evaluate the prognostic factors for intrahepatic recurrence of hepatocellular carcinoma (HCC) after curative resection. Methods: Of 297 patients with HCC who underwent curative resection between 1998 and 2007, 145 had intrahepatic recurrence, and 125 of these were enrolled in this study. We analyzed the relationships between overall survival after HCC recurrence and 20 variables at initial hepatectomy and recurrence. Results: Recurrent HCC was treated by repeat hepatectomy (Re-Hr, n = 29), radiofrequency ablation (RFA, n = 58), or transarterial chemoembolization (TAE, n = 38). Complete tumor control (CTC) by Re-He and RFA was selected for 70% of patients. RFA-treated patients had more tumors, smaller tumors, and poorer liver function at recurrence than the Re-Hr group. The overall 1-, 3-, and 5-year post-recurrence survival rates (SR) were 93.1, 66.8, 58.1%; 94.7, 75.1, 48.3%; and 80.1, 22.5, 0%, respectively, in the Re-Hr, RFA, and TAE groups. The SR was better for Re-Hr and RFA than for TAE ( p < 0.0001). Outcomes were similar in Re-Hr and RFA, regardless of recurrent tumor size. Multivariate analysis identified Child-Pugh grade B, AFP ≥100 ng/ml at recurrence, recurrent tumor size ≥3 cm, tumor number ≥3, and CTC as significant prognostic factors for overall post-recurrence survival. A scoring system using 1 point for each patient-background factor provided a well-categorized predictive model. The overall 3-/5-year post-recurrence SRs were 83.1/59.3%, 64.1/41.9%, 42.0/18.0%, and 13.6/0% at risk number (R) R0, R1, R2, and R3/4, respectively ( p < 0.05). Conclusions: Significant prognostic factors for intrahepatic recurrent HCC are poor hepatic reserve, AFP, recurrent tumor size and number, and CTC. Selection of treatment modality for intrahepatic recurrence requires the clinician to be mindful of the predictive factors and to control tumors aggressively by adequate treatment, selected by balancing various conditions. [ABSTRACT FROM AUTHOR]

Background/Purpose: The purpose of this study was to identify risk factors for major morbidity after hepatectomies for hepatocellular carcinoma (HCC). Methods: Univariate and multivariate analyses of risk factors for major morbidity were performed in 293 patients who underwent hepatectomy for HCC between 2001 and 2008. Results: Two hundred and forty-three patients (82.9%) underwent an anatomic hepatectomy, and a repeat hepatectomy was performed in 50 patients (17.1%). The prevalences of bile leakage and intraabdominal abscess were 12.9% and 9.2%, respectively. The risk factor for bile leakage was an operative time ≥ 300 min and the risk factor for intraabdominal abscess was a repeat hepatectomy (odds ratios = 4.9 and 5.3, respectively). The main cause of bile leakage that made endoscopic therapy or percutaneous transhepatic biliary drainage necessary was a latent stricture of the biliary anatomy that had existed preoperatively, caused by previous treatments for HCC. Methicillin-resistant Staphylococcus aureus was the main causative bacteria of intraabdominal abscess after repeat hepatectomies. Conclusions: Our recent series revealed that prolonged operative time and repeat hepatectomy were independent risk factors for bile leakage and intraabdominal abscess, respectively, after hepatectomies for HCC. Preoperative assessment of the biliary anatomy should be considered for patients who have had previous multiple treatments for HCC, including hepatectomy, to reduce bile leakage that makes invasive treatment necessary. [ABSTRACT FROM AUTHOR]

Background/purpose: We present the cases of two patients with hepatocellular carcinoma (HCC) beyond the Milan criteria (MC) who underwent living-donor liver transplantation (LDLT) combined with aggressive hepatic venacaval resection and replacement of the hepatic inferior vena cava (IVC) by an artificial vascular graft. The aim of the resection and replacement of the hepatic IVC was to resect completely a latent cancer adjacent to the hepatic IVC and to avoid micrometastasis via the hepatic veins during increased manipulation of the native liver with HCC. Methods: First, the hepatic hilus was dissected and the infrahepatic IVC was encircled. After minimum mobilization of the liver, the common orifice of the middle and left hepatic veins and suprahepatic IVC was encircled. Venovenous bypass (VVB) was started to stabilize systemic hemodynamics. After cross-clamping of the infrahepatic and suprahepatic IVC, the IVC was divided at the site just below the confluence of the common orifice of the middle and left hepatic veins and its infrahepatic site. Then, all retroperitoneal attachments of the right lobe were dissected and the native liver was resected with the retrohepatic IVC. The IVC was replaced by a ringed expanded polytetrafluoroethylene (e-PTFE) graft. Infrahepatic venous recirculation ended the VVB. An extended left-lobe graft was implanted. The e-PTFE grafts were covered with the greater omentum to avoid infection. Results: The operations were completed safely. The postoperative courses were free of complications related to the reconstruction of the hepatic IVC. One patient developed recurrence in the left adrenal gland. Conclusion: LDLT combined with hepatic venacaval resection and replacement by an e-PTFE graft for HCC beyond the MC could be safe and feasible under VVB. Further studies are needed to confirm to what extent this procedure could prevent post-transplant recurrence in HCC beyond the MC. [ABSTRACT FROM AUTHOR]

Aim: We evaluated the expression of hepatitis C virus (HCV) antigen on liver grafts by immunohistochemical staining (IHS) using IG222 monoclonal antibody (mAb) against HCV-envelope 2 (E2). Methods: The study material was 84 liver biopsy specimens obtained from 28 patients who underwent living donor liver transplantation (LDLT) for HCV infection. The biopsy samples were examined histopathologically, and by IHS using IG222 mAb against HCV-E2. Serum HCV-RNA level was measured in all patients. The IHS grades were compared among the three groups classified according to the time elapsed from LDLT (at 1–30, 31–179 and ≥180 days post-LDLT) and among four post-transplant conditions, including acute cellular rejection (ACR). Results: Immunoreactivity to IG222 was detected in 78.6% of the specimens obtained during the first month after LDLT, and there were no significant differences on the IHS grades between the three groups classified according to the time elapsed from LDLT. The IHS grades were significantly stronger in definite recurrent HCV ( n = 12) and probable recurrent HCV ( n = 7) than in definite ACR ( n = 7) and other complications ( n = 8). There were no significant differences in serum HCV-RNA levels among the four post-transplant conditions. There was no significant correlation between the IHS grades using IG222 mAb and serum HCV-RNA levels when data of 84 liver biopsy specimens were analyzed. Conclusions: Constant HCV-E2 expression was observed in liver biopsy specimens obtained 1 month or longer. The strong HCV-E2 expression on liver grafts were associated with recurrent hepatitis C after LDLT, but the serum HCV-RNA levels were not. [ABSTRACT FROM AUTHOR]

The purpose of this study was to analyze various risk factors and to assess the preoperative risk score, which can predict the prognosis after living donor liver transplantation (LDLT). From February 2002 to August 2007, 84 adult to adult living donor liver transplantation donors and recipients were analyzed. First, the donor, recipient, and intraoperative factors were examined by univariate and multivariate analyses. We then gave a score of one point for each significant marginal factor (total point scores were called “risk score”) and each risk score was examined by univariate analyses. Recipients with the donor age 50 years or older, Model for End-Stage Liver Disease (MELD) score (≥21), and hepatitis C virus-positive status had a significantly poor survival. Recipients between the risk score of 0 vs. scores of 2 + 3 ( p < 0.001, log-rank) and risk score of 1 vs. scores of 2 + 3 ( p = 0.003, log-rank) had significantly different survival. Preoperative assessment of the risk score might help to predict recipient outcomes after living donor liver transplantation. [ABSTRACT FROM AUTHOR]

Background and Aim: The mechanism of injury in steatotic liver under pathological conditions been extensively examined. However, the mechanism of an impaired regeneration is still not well understood. The aim of this study was to analyze the mechanism of impaired regeneration of steatotic liver after partial hepatectomy (PH). Methods: db/db fatty mice and lean littermates were used for the experiments. Following 70% PH, the survival rate and recovery of liver mass were examined. Liver tissue was histologically examined and analyzed by western blotting and RT-PCR. Results: Of 35 db/db mice, 25 died within 48 h of PH, while all of the control mice survived. Liver regeneration of surviving db/db mice was largely impaired. In db/db mice, mitosis of hepatocytes after PH was disturbed, even though proliferating cell nuclear antigen (PCNA) expression (G1 to S phase marker) in hepatocytes was equally observed in both mice groups. Interestingly, phosphorylation of Cdc2 in db/db mice was suppressed by reduced expression of Wee1 and Myt1, which phosphorylate Cdc2 in S to G2 phase. Conclusions: In steatotic liver, cell-cycle-related proliferative disorders occurred at mid-S phase after PCNA expression. Reduced expression of Wee1 and Myt1 kinases may therefore maintain Cdc2 in an unphosphorylated state and block cell cycle progression in mid-S phase. These kinases may be critical factors involved in the impaired liver regeneration in fatty liver. [ABSTRACT FROM AUTHOR]

Presents the case of a boy with human herpesvirus 6 (HHV-6) fulminant hepatic failure who was treated by living donor liver transplantation. Medical history of the patient; Details of the identification of an etiologic agent for the disease; Background on the detection of HHV-6 DNA in serum samples.

Emphysematous cholecystitis is a rare, but life-threatening, form of acute cholecystitis caused by gas-forming organisms in the gallbladder. A 73-year-old male patient with type 2 diabetes mellitus complicated with neuropathy associated with schizophrenia was admitted to Okayama University Hospital, Okayama, Japan, because of a high fever and general malaise. On the fourth hospital day, despite normal liver function tests and little abdominal pain, his abdominal computed tomography showed huge gas formation in the gallbladder lumen along with a dilated gallbladder with a thickened wall, consistent with emphysematous cholecystitis. The patient underwent an emergency open cholecystectomy. Few abdominal symptoms appeared because of the hyposensitivity to pain caused by not only diabetic neuropathy, but also antipsychotic agents the patient was taking for schizophrenia. Emphysematous cholecystitis should be taken into consideration for the differential diagnosis of high fever in diabetic patients with schizophrenia, irrespective of the level of liver function tests and clinical symptoms. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor about occult hepatocelular carcinoma with high fucosylated alpha-fetoprotein (AFP).