Circulating exosomal noncoding RNAs as prognostic biomarkers in human hepatocellular carcinoma.

Exosomal noncoding RNAs (ncRNAs) have unique expression profiles reflecting the characteristics of a tumor, and their role in tumor progression and metastasis is emerging. However, the significance of circulating exosomal ncRNAs in the prognosis of hepatocellular carcinoma (HCC) remains to be elucidated. We therefore determined the prognostic significance of circulating exosomal ncRNAs (miRNA-21 and lncRNA-ATB) for human HCC. This prospective study enrolled 79 HCC patients between October 2014 and September 2015. Exosomes were extracted from serum samples using the ExoQuick Exosome Precipitation Solution. To validate the isolation of the exosomes from serum, immunoblotting for exosome markers and characterization of nanoparticle using NanoSight were performed. NcRNAs were isolated from exosomes using the miRNeasy serum/plasma micro kit. Both circulating exosomal miRNA-21 and lncRNA-ATB were related to TNM stage and other prognostic factors, including the T stage and portal vein thrombosis. Multivariate analysis using the Cox regression test identified that both higher miRNA-21 and higher lncRNA-ATB were independent predictors of mortality and disease progression, along with larger tumor size and higher C-reactive protein (all p < 0.05). The overall survival and progression-free survival were significantly lower in patients with higher circulating levels of exosomal miRNA-21 (≥0.09) and lncRNA-ATB (≥0.0016) (log-rank test: p < 0.05). In conclusion, our study has provided strong evidence that circulating exosomal ncRNAs (miRNA-21 and lncRNA-ATB) are novel prognostic markers and therapeutic targets for HCC.

Effect of intermittent hepatic inflow occlusion with the Pringle maneuver during donor hepatectomy in adult living donor liver transplantation with right hemiliver grafts: a prospective, randomized controlled study.

To evaluate the effects of intermittent hepatic inflow occlusion (IHIO) during donor hepatectomy for living donor liver transplantation (LDLT) in recipients and donors, we performed a single-center, open-label, prospective, parallel, randomized controlled study. Adult donor-recipient pairs undergoing LDLT with right hemiliver grafts were randomized into IHIO and control groups (1:1). In the IHIO group, IHIO was performed during donor hepatectomy. The primary endpoint was the peak serum alanine aminotransferase (ALT) concentration in the recipients within 5 days after the operation. Blood samples for measurements of interleukin-6 (IL-6), IL-8, tumor necrosis factor α (TNF-α), and hepatocyte growth factor (HGF) were taken from the donors and the recipients during the operation and postoperatively. Biopsy samples for measurements of caspase-3 and malondialdehyde (MDA) were taken from the donors and the recipients. In all, 50 donor-recipient pairs (ie, 25 pairs in each group) completed this study. The mean peak serum ALT levels within 5 days after the operation did not differ in the recipients between the 2 groups (P = 0.32) but were higher in the donors of the IHIO group (P = 0.002). There were no differences in the prothrombin times or total bilirubin levels in the recipients or donors between the 2 groups. The amount of blood loss during donor hepatectomy was significantly lower in the IHIO group versus the control group (P = 0.02). The mean hospital stay for donors was 19.3 ± 7.2 days in the control group and 15.8 ± 4.6 days in the IHIO group (P = 0.046). There were no in-hospital deaths within 1 month and no cases of primary nonfunction or initially poor function in the 2 groups. The concentrations of IL-6, IL-8, TNF-α, and HGF did not differ between the 2 groups, nor did the concentrations of caspase-3 and MDA. In conclusion, although we found differences in postoperative peak serum ALT levels in donors, donor hepatectomy with IHIO for LDLT using a right hemiliver graft with a graft-to-recipient body weight ratio > 0.9% and <30% steatosis can be a tolerable procedure for donors and recipients.

What makes acute cholecystitis recur after removing the percutaneous cholecystostomy tube?

ABSTRACT: Percutaneous transhepatic gallbladder drainage (PTGBD) is an alternative treatment option for acute cholecystitis. However, the disease may recur after PTGBD catheter removal. This study aimed to evaluate the role of endoscopic sphincterotomy and other risk factors in reducing the recurrence of cholecystitis.We retrospectively analyzed data from 1088 patients who underwent PTGBD for cholecystitis at Kyungpook National University Hospital, Republic of Korea, between January 2011 and April 2018.A total of 115 patients were enrolled in the study. The recurrence rate of cholecystitis was 17.4% (n = 20) during a median follow-up period of 1159 (range, 369-2774) days. Endoscopic biliary sphincterotomy did not significantly affect the recurrence rate of cholecystitis (P = .561). In multivariable analysis, cystic duct stones (P = .013) and PTGBD catheter migration before the prescheduled removal time (P = .002) were identified as independent risk factors for cholecystitis recurrence after PTGBD.To reduce post-PTGBD recurrence in cholecystitis, caution must be exercised to avoid inadvertent dislodging of the PTGBD catheter. In cases of cholecystitis with cystic duct stones, cholecystectomy should be considered only after careful assessment of postoperative risks. Instead, transluminal endoscopic gallbladder drainage could represent a promising option for the prevention of recurrent cholecystitis.

Prognostic factors after early recurrence in patients who underwent curative resection for hepatocellular carcinoma.

BACKGROUND: The prognosis of the patients with early recurrence after curative hepatectomy for hepatocellular carcinoma (HCC) is usually dismal. METHODS: One hundred twenty-four patients underwent curative resection for HCC at Kyungpook National University Hospital from January 2002 to December 2006. An early recurrence was defined as a recurrence within 2 years after a curative resection. The risk factors associated with an early recurrence were analyzed as well as other risk factors correlated with survival after early recurrence. RESULTS: Early disease recurrence developed in 56 patients (45.2%). The risk factors associated with an early recurrence were a tumor size larger than 5 cm (P = 0.001) and the presence of tumor micrometastasis (P < 0.001). The 1 year/2 year overall survival, after early recurrence, was 57.0%/41.0% and the preoperative α-fetoprotein, C-reactive protein (CRP), tumor size, macroscopic vascular invasion, and number of tumors were associated with survival on the univariate analysis. The multivariate analysis showed that the independent risk factors for survival, after early disease recurrence, were a preoperative CRP >1.0 mg/dl and macroscopic vascular invasion. (P = 0.004, P < 0.001, respectively). CONCLUSION: The preoperative CRP and macroscopic vascular invasion were associated with the aggressiveness of early recurrent HCC.

Synchronous gallbladder metastasis of renal cell carcinoma presenting as a gallbladder polyp: A case report.

RATIONALE: Gallbladder polyps are common in the general population, but gallbladder metastasis of renal cell carcinoma (RCC) is very rare. In a patient with RCC diagnosed with a small gallbladder polyp that does not meet the traditional size criteria, the surgeon faces a dilemma of whether cholecystectomy should be performed given the possibility of metastasis. PATIENT CONCERNS: A 55-year-old man who had received a left nephrectomy for RCC presented with a gallbladder polyp that was noted at the time of the nephrectomy. Imaging showed the maximum diameter of the polyp had increased from 5 mm to 24 mm in the 40 months after the initial diagnosis. DIAGNOSIS: Pathological and immunohistology findings confirmed the gallbladder polyp as a metastasis of clear-cell RCC. INTERVENTIONS: : We performed a laparoscopic cholecystectomy. OUTCOMES: Even though the synchronous solitary gallbladder metastasis was left untreated and a cholecystectomy was not performed over the 40 months, no metastasis occurred in other sites. The patient is free from disease 10 months after the cholecystectomy. LESSONS: Solitary gallbladder metastasis of RCC may have more favorable outcomes than typical metastases. Although gallbladder metastasis of RCC occur rarely, it can occur, and any changes in gallbladder polyps in RCC patients should be managed under a strong suspicion of metastasis.

Long interspersed nuclear element-1 hypomethylation is associated with poor outcomes via the activation of ST18 in human hepatocellular carcinoma.

ABSTRACT: The level of long interspersed nuclear element-1 (LINE-1) methylation, representing the global deoxyribonucleic acid methylation level, could contribute to the prognosis of cancer via the activation of oncogenes. This study was performed to evaluate the prognostic implications of LINE-1 hypomethylation in patients with hepatocellular carcinoma (HCC) and the possible mechanisms related to oncogene activation.Seventy-seven HCC patients between October 2014 and September 2015 were enrolled in this prospective study. Quantitative pyrosequencing was performed to assess the LINE-1 methylation level of HCC and matched non-HCC tissue samples. The expression of suppression of tumorigenicity 18 was measured by immunohistochemistry and its correlation with LINE-1 methylation levels was examined.LINE-1 was significantly hypomethylated in the HCC tissue compared with the matched nontumor tissue (64.0 ± 11.6% vs 75.6 ±â€Š4.0%, P < .001). LINE-1 hypomethylation was an independent risk factor for overall survival (hazard ratio = 27.291, P = .032) and disease progression (hazard ratio = 5.298, P = .005). The expression of suppression of tumorigenicity 18 was higher in the hypomethylated LINE-1 HCC tissue than the hypermethylated LINE-1 tumor tissue (P = .030).LINE-1 hypomethylation may serve as a potential prognostic marker for patients with HCC.

Technical review of a single-center experience of biliary recanalization for liver transplantation-related benign biliary stricture.

PURPOSE: To review a single-center experience of percutaneous biliary recanalization for liver transplantation-related benign biliary stricture, particularly focusing on the technical aspect. METHOD: Twenty-three recipients of liver transplantation (LT) with 27 benign biliary strictures underwent percutaneous recanalization using a step-by-step technique from June 2017 to March 2020. The step-by-step technique includes a hairy wire or an usual 0.035-inch wire passage, a coaxial system, supporting catheters of various shapes and wires, and an extraluminal passage. The success rate of percutaneous biliary recanalization, degree of stricture, interval between LT and biliary recanalization, procedure time, number of sessions, and recanalization techniques were analyzed. RESULTS: Among the 27 lesions, 26 (96 %) were successfully recanalized using a percutaneous approach without major complications. Of the 27 lesions, 8 were complete obstructions and 19 were partial obstructions. Consequently, the average interval between LT and biliary recanalization was 28.8 ±â€¯42.7 months (range, 2-192 months). The average procedure time was 50 ±â€¯65 min (range, 8-345 min). The average number of sessions was 1.4 ±â€¯1 (range, 1-6). The case distribution for the used recanalization techniques was as follows: twelve cases utilized step 1, 10 utilized step 2, 4 utilized step 3, and only 1 case utilized step 4. The complete obstruction group required a more advanced technique and spent more recanalization time than the partial obstruction group. CONCLUSIONS: The step-by-step percutaneous biliary recanalization technique had a high success rate without major complications. According to the patient's biliary anatomy appropriate selection of an angled 5-Fr support catheter and wire is essential in increasing the recanalization success rate.

Plasma Long Noncoding RNA LeXis is a Potential Diagnostic Marker for Non-Alcoholic Steatohepatitis.

Non-invasive diagnostic markers are needed to ease the diagnosis of non-alcoholic steatohepatitis (NASH) among patients with non-alcoholic fatty liver disease (NAFLD). The long noncoding RNA (lncRNA) LeXis is related to cholesterol metabolism and hepatic steatosis in mice, and its batch genome conversion in humans is TCONS_00016452. Here, we aimed to evaluate the potential of lncRNA LeXis as a non-invasive diagnostic marker for NASH. We analyzed a total of 44 NAFLD patients whose diagnosis was confirmed by a pathologist through analysis of a percutaneous liver biopsy. The expression of LeXis in the plasma of NAFLD patients with and without NASH was compared using quantitative real-time polymerase chain reaction. The expression of plasma LeXis was significantly higher in patients with NASH than in those with NAFL (8.2 (5.0-14.9); 4.6 (4.0-6.6), p = 0.025). The area under the receiver operating characteristic curve was 0.743 (95% CI 0.590-0.895, p < 0.001), and a sensitivity of 54.3% and specificity of 100% could be achieved for NASH diagnosis. Low LeXis was independently associated with NASH diagnosis in patients with NAFLD (p = 0.0349, odds ratio = 22.19 (5% CI, 1.25-395.22)). Therefore, circulating lncRNA LeXis could be a potential non-invasive diagnostic biomarker for NASH.

Expression of the Long Noncoding RNA GAS5 Correlates with Liver Fibrosis in Patients with Nonalcoholic Fatty Liver Disease.

BACKGROUND: Advanced liver fibrosis is the most important prognostic factor in nonalcoholic fatty liver disease (NAFLD). The long noncoding RNA (lncRNA), growth arrest-specific transcript 5 (GAS5), is associated with the inhibition of liver fibrogenesis, and its levels are decreased in cirrhotic liver. METHODS: We analyzed 51 patients with NAFLD, the diagnosis of which was confirmed by liver biopsy. Expression of GAS5 in both the liver and plasma of the patients was analyzed using a quantitative real-time polymerase chain reaction according to the fibrosis stage. RESULTS: Plasma GAS5 expression was significantly higher in patients with advanced fibrosis than in those without. As the fibrosis progressed, GAS5 expression in plasma increased, with the exception of that in cirrhotic livers. Plasma levels of GAS5 were lower in patients with cirrhosis than in those with advanced fibrosis. CONCLUSION: Elevated circulating levels of the lncRNA GAS5 are associated with the progression of liver fibrosis prior to the development of cirrhosis.

A Single Center Experience for a Feasibility of Totally Laparoscopic Living Donor Right Hepatectomy.

Purpose: Donor safety is the most important problem of living donor liver transplantation (LDLT). Although laparoscopic liver resection has gained popularity with increased surgical experience and the development of laparoscopes and specialized instruments, a totally laparoscopic living donor right hepatectomy (LDRH) technique has not been investigated for efficacy and feasibility. We describe the experiences and outcomes associated with LDRH in adult-to-adult LDLT in order to assess the safety of the totally laparoscopic technique in donors. Methods: Between May 2016 and July 2017, we performed hepatectomies in 22 living donors using a totally laparoscopic approach. Among them, 20 donors underwent LDRH. We retrospectively reviewed the medical records to ascertain donor safety and the reproducibility of LDRH; intra-operative and post-operative results including complications were demonstrated after performing LDRH. Results: The median donor age was 29 years old and the median body mass index was 22.6 kg/m2. The actual graft weight was 710 g and graft weight/body weight (GRWR) was 1.125. No donors required blood transfusion, conversion to open surgery, or reoperation. The postoperative mortality was nil and postoperative complications were identified in two donors. One had fluid collection in the supra-pubic incision site for graft retrieval and the second had a minor bile leakage from the cutting edge of the right hepatic duct stump. All the liver function tests returned to normal ranges within one month. Conclusion: LDRH is a feasible operation owing to low blood loss and few complications. However, LDRH can be initially attempted after attaining sufficient experience in laparoscopic hepatectomy and LDLT techniques.

[Expression of vascular endothelial growth factor (VEGF) family members and prognosis after hepatic resection in HBV-related hepatocellular carcinoma].

BACKGROUND/AIMS: Human hepatocellular carcinoma (HCC) is a hypervascular tumor, and vascular endothelial growth factor (VEGF) plays a key role in the regulation of tumor-associated angiogenesis. In this study, we analyzed the significance of the expression of VEGF family members on the prognosis and clinicopathologic progress of HCC. METHODS: Surgically resected specimens of HCC and noncancerous liver tissue were obtained from 323 patients with HCC, and VEGF mRNA was examined by quantitative reverse transcriptase-polymerase chain reactions (RT-PCRs). Patients who were seropositive for hepatitis B surface antigen were selected for the analysis (n=208). The VEGF(tumor)/GAPDH (glyceraldehyde-3-phosphate dehydrogenase)(tumor)/VEGF(nontumor)/GAPDH(nontumor) ratio was calculated using a quantitative RT-PCR assay, and the relationships between the expressions of VEGF family members and clinicopathologic parameters were analyzed to evaluate their significance in the prognosis of HCC. RESULTS: The disease-free survival was significantly worse in the high-VEGF-A group than in the low-VEGF-A group (P=0.035), whereas VEGF-A expression was not significantly related to overall survival (P=0.172). The factors significantly related to poor prognosis in univariate analysis were tumor size, portal vein invasion, microvascular thrombi, intrahepatic metastasis, tumor capsule invasion, liver capsule invasion, preoperative serum albumin level, and VEGF-A ratio. Multivariate analysis showed that a poor prognosis in HCC patients was significantly related to portal vein invasion (hazard ratio=3.381, P<0.001), intrahepatic metastasis (hazard ratio=2.379, P<0.001), tumor size (hazard ratio=1.834, P=0.003), and preoperative serum albumin level (hazard ratio=2.050, P=0.006). CONCLUSIONS: Our study showed that the expression of VEGF-A is positively correlated with the recurrence rate of HCC after curative resection. Therefore, a high expression of VEGF-A might be predictive of HCC recurrence after curative resection.

ABO incompatible living donor liver transplantation using dual grafts and pure laparoscopic donor right hepatectomy: A case report.

RATIONALE: Because of the shortage of deceased donors, living donor liver transplantation (LDLT) has become the main procedure to treat patients with end-stage liver disease in Asian countries. However, many potential donors are excluded because of donor safety and graft volume issues. In addition, large abdominal wounds after open surgery for hepatectomy could be a reason for hesitating to agree to liver donation, particularly when attempting to recruit young female donors. PATIENT CONCERNS: On volumetric computed tomography (CT) examination, remnant liver volume was too small to guarantee the safety of the male donor, and the right hemiliver volume of the female donor was not sufficient to meet the recipient's metabolic demand. The young female donor also worried about a large abdominal wound following open surgery. INTERVENTIONS: We performed ABO-incompatible LDLT using dual grafts and right-sided graft was obtained by pure laparoscopic donor right hepatectomy in a young female donor. OUTCOMES: The postoperative course was uneventful in both donors and the recipient is presently doing well in satisfactory condition 7 months after liver transplantation. LESSONS: We overcame these volumetric and cosmetic issues through dual living donor liver grafts using a combination of conventional surgery for 1 donor and laparoscopic right hepatectomy for a second ABO-incompatible donor. We think this procedure can be a good option for the expansion of donor pools.

Tenofovir, entecavir, and lamivudine in patients with severe acute exacerbation and hepatic decompensation of chronic hepatitis B.

OBJECTIVE: To compare the efficacy of and mortality after lamivudine (LAM), tenofovir (TDF), and entecavir (ETV) treatment in patients with severe acute chronic hepatitis B (CHB) exacerbation. METHODS: We analyzed 91 patients with severe acute CHB exacerbation treated with LAM (n=28), TDF (n=26), or ETV (n=37) for 10 years. The primary endpoint was overall mortality or liver transplantation (LT) by 48 weeks. The determined predictors of mortality, virologic and biochemical responses, and drug resistance were also evaluated. RESULTS: The overall mortality or LT rate was not significantly different among the LAM (14.3%), ETV (10.8%), and TDF (3.8%) groups (P=0.435). In the multivariate analysis, the occurrence of ascites (hazard ratio [HR] 10.467, 95% confidence interval [CI] 1.596-68.645, P=0.014) and model for end-stage liver disease (MELD) scores above 25 (HR 28.920, CI 4.719-177.251, P=0.000) increased the risk of mortality or LT. All groups showed similar biochemical responses (P=0.134), virologic responses (HBV DNA <116copies/mL, P=0.151), and HBeAg seroconversion (P=0.560). Antiviral resistance emerged in five patients treated with LAM by 48 weeks (17.9%, P=0.003). CONCLUSION: LAM, ETV, and TDF selection is not related with mortality and LT in patients with severe acute CHB exacerbation and hepatic decompensation. To reduce mortality, patients with ascites and MELD scores above 25 should be considered for LT.

Comparison of acoustic radiation force impulse elastography and transient elastography for prediction of hepatocellular carcinoma recurrence after radiofrequency ablation.

BACKGROUND: To compare the clinical value of acoustic radiation force impulse (ARFI) elastography and transient elastography (TE) for hepatocellular carcinoma (HCC) recurrence prediction after radiofrequency ablation (RFA) and to investigate other predictors of HCC recurrence. PATIENTS AND METHODS: Between 2011 and 2016, 130 patients with HCC who underwent ARFI elastography and TE within 6 months before curative RFA were prospectively enrolled. Independent predictors of HCC recurrence were analyzed separately using ARFI elastography and TE. ARFI elastography and TE accuracy to predict HCC recurrence was determined by receiver operating characteristic curve analysis. RESULTS: Of all included patients (91 men; mean age, 63.5 years; range: 43-84 years), 51 (42.5%) experienced HCC recurrence during the follow-up period (median, 21.9 months). In multivariable analysis using ARFI velocity, serum albumin and ARFI velocity [hazard ratios: 2.873; 95% confidence interval (CI): 1.806-4.571; P<0.001] were independent predictors of recurrence, and in multivariable analysis using TE value, serum albumin and TE value (hazard ratios: 1.028; 95% CI: 1.013-1.043; P<0.001) were independent predictors of recurrence. The area under the receiver operating characteristic curve of ARFI elastography (0.821; 95% CI: 0.747-0.895) was not statistically different from that of TE (0.793; 95% CI: 0.712-0.874) for predicting HCC recurrence (P=0.827). The optimal ARFI velocity and TE cutoff values were 1.6 m/s and 14 kPa, respectively. CONCLUSION: ARFI elastography and TE yield comparable predictors of HCC recurrence after RFA.

Clinical significance of microRNA-21 expression in disease progression of patients with hepatocellular carcinoma.

AIM: Aberrant microRNA (miR) expression is associated with hepatocellular carcinoma (HCC). MATERIALS & METHODS: Here, we investigated the clinical significance of miR-21 and miR-31 for HCC-specific prognostic effect. HCC patients (n = 93) who underwent liver biopsy or surgical resection were enrolled, and HCC tissues and paired adjacent nontumor liver tissues were collected and analyzed for miRs expression. RESULTS: MiR-21 expression was significantly upregulated in HCC tissues relative to nontumor tissues. Both miR-21 and miR-31 expression in HCC tissues did not predict overall survival; however, miR-21 was considered an independent predictor of disease progression together with portal vein thrombosis and higher Barcelona Clinical Liver Cancer stage. CONCLUSION: Elevated miR-21 expression might represent a biomarker for HCC prognosis.

Practical experience of a no abdominal drainage policy in patients undergoing liver resection.

BACKGROUND/AIMS: Routine use of abdominal drainage after liver resection is controversial. The aim of this study was to investigate the practical application of a "no abdominal drainage" policy for consecutive patients undergoing hepatic resection. METHODOLOGY: The present trial included 60 consecutive patients who underwent elective hepatic resection. Fifty-two patients underwent no abdominal drainage, and in the remaining eight drainage was necessary because of gross contamination of the surgical field associated with bilioenteric anastomosis, uncontrollable bile leakage from the cut surface of the liver, or the surgeon's preference. Patient demographics, intraoperative data, and postoperative complications and mortality were evaluated. RESULTS: There was no hospital death. Eight complications occurred in 8 patients in the no-drainage group (morbidity rate 15.4%, 8/52): bleeding, abscess, ascites requiring peritoneal tap, pleural effusion requiring thoracentesis, and pneumonia in one case each, and three cases of wound infection. Three complications were encountered in 2 patients in the drainage group (morbidity rate 25%, 2/8): bleeding, infected biloma and pleural effusion in one case each. Postoperative hospital stay tended to be shorter in the no-drainage group (10.7 +/- 3.9 days) than in the drainage group (15.6 +/- 6.4 days) (p = 0.07). Considering early uneventful removal of the drain on the morning of postoperative day 1, half of the drained patients might have not required drainage. Furthermore, in the setting of concomitant bilioenteric anastomosis (n=4), one patient underwent hepatectomy uneventfully without drainage, and two of three patients with drainage had their drains removed successfully on day 1. The third patient retained the drain for an unnecessarily long period, but did not develop subsequent complications. CONCLUSIONS: Our data support the view that prophylactic abdominal drainage is unnecessary in most patients who undergo elective hepatic resection. Bilioenteric anastomosis may not be a contraindication for a no abdominal drainage policy.

Successful intermittent application of the Pringle maneuver for 30 minutes during human hepatectomy: a clinical randomized study with use of a protease inhibitor.

BACKGROUND/AIMS: There is experimental evidence that the liver can safely tolerate a cycle involving application of the Pringle maneuver for 30 minutes each time. METHODOLOGY: One hundred and twenty patients who underwent elective hepatectomy were randomly assigned to two groups of intermittent occlusion (30-min or 15-min Pringle group, n=60 each). A synthetic protease inhibitor (gabexate mesilate, GM, 2 mg/kg/h) was administered to pharmacologically alleviate visceral congestion, accompanied by hepatic pedicle clamping. Intraoperative data, liver function parameters and portal plasma levels of the inflammatory cytokine, interleukin (IL)-6 (a marker reflecting the status of visceral congestion), were examined as well as the postoperative course. Additionally, ten more patients randomly underwent right hepatectomy without GM, in order to clarify the influence of this agent on the present outcomes. RESULTS: The two groups of patients were comparable in terms of preoperative assessments, hepatic inflow occlusion time, extent of resection and background liver conditions. The 30-min Pringle group showed less blood loss during surgery (p=0.02) with a tendency for better postoperative mortality and morbidity. The postoperative liver functions were similar between the two groups. The portal plasma levels of IL-6 during pedicle clamping did not differ significantly between the two groups. When GM was not used, the 30-min intermittent Pringle maneuver induced a two-fold rise in serum transaminase levels on day 1 compared with the 15-min group. CONCLUSIONS: Our study indicates that intermittent application of the Pringle maneuver for 30 minutes each time can be accomplished effectively and safely for human hepatectomy, when combined with use of a protease inhibitor.

Intrahepatic splenic tissue without medical history of splenic injury or splenectomy.

Only a few cases of intrahepatic splenic tissue have so far been reported in the English literature. Those cases were developed after splenic injury or a splenectomy. We report here a case of intrahepatic splenic tissue which has two distinctive features compared to previous literature. A 59-year-old female who previously had no medical history of splenic injury or splenectomy underwent hepatic resection for intrahepatic tumor mimicking hepatocellular carcinoma. However, pathologic examination revealed it as intrahepatic splenic tissue directly abutted to the normal liver tissue without a capsule. Lacking an invasive diagnostic modality, the diagnosis of intrahepatic splenic tissue without an accompanying medical history is very difficult.

Totally laparoscopic associating liver partition and portal vein ligation for staged hepatectomy using anterior approach in HCC patient with Type II portal vein anomaly: a case report.

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has gradually developed because of rapid hypertrophy of the future liver remnant volume (FLR) in spite of high morbidity. To minimize the patient's postoperative pain and morbidity including wound complication caused by two consecutive major abdominal operations, we adopted a totally laparoscopic approach and used a composite mesh graft. Also, to maximize the oncologic efficacy, we adopted the "anterior approach" technique. A 44-year-old woman with large hepatitis B-related hepatocellular carcinoma (HCC) in her right lobe was transferred to our hospital for surgical treatment. Preoperatively predicted FLR by a CT scan was 21% and type II portal vein anomaly was detected. A totally laparoscopic approach was planned. During the first stage operation, right anterior and posterior portal veins were meticulously dissected and tied. After parenchymal transection by the "anterior approach" technique, two glissonian pedicles of the right liver were individually isolated. A composite mesh graft was used to prevent severe adhesion on both liver partition surfaces. During the second-stage operation, 9 days after the first stage operation, the two isolated glissonian pedicles were initially transected. After full mobilization of the right lobe, the right hepatic vein was also transected. The right lobe was removed through the Pfannenstiel incision. She was discharged 7 days after the second stage operation. Her postoperative course was uneventful and there was no HCC recurrence for 15 months after hepatectomy. A totally laparoscopic ALPPS procedure can be a feasible technique that ensures patient safety and oncologic superiority, even in patients with complicated anatomical variation.

Pure laparoscopic donor right hepatectomy in a living donor with type 3a biliary variation: A case report.

RATIONALE: With refinements in the operative technique, laparoscopic surgery has become the standard practice for liver resection. In the field of living donor liver transplantation, a few centers adopted laparoscopic surgery as an alternative to conventional open donor hepatectomy, and the application of pure laparoscopic donor right hepatectomy has been limited to the donors with simple, favorable biliary anatomy. PATIENT CONCERNS: The candidate donor was a 19-year-old woman with type 3a bile duct variation. INTERVENTIONS: After confirming precise cutting points under the guidance of a radiopaque marker rubber band, the bile ducts were divided and the remnant stumps were closed with suture and clipping using Hem-o-lok, respectively. OUTCOMES: The postoperative course was uneventful and she was satisfactory 6 months after surgery. LESSONS: A laparoscopic donor hepatectomy for the living donor with biliary variation was feasible. Biliary variations are commonly encountered during living donor surgery, and we think that such variations in laparoscopic donor hepatectomy need to be overcome to expand the selection criteria.