Yo Ichi Yamashita

Bile Leakage After Hepatic Resection

ObjectiveTo identify the perioperative risk factors for postoperative bile leakage after hepatic resection, to evaluate the intraoperative bile leakage test as a preventive measure, and to propose a treatment strategy for postoperative bile leakage according to the outcome of these patients. Summary Background DataBile leakage remains a common cause of major complications after hepatic resection. MethodsBetween January 1985 and June 1999, 781 hepatic resections without bilioenteric anastomosis were performed at the authors’ institution. Perioperative risk factors related to postoperative bile leakage were identified using univariate and multivariate analysis. The characteristics of patients with intractable bile leakage and the effect of intraoperative bile leakage test were also examined. Management was evaluated in relation to the outcomes and the clinical characteristics of the patients with bile leakage. ResultsBile leakage developed in 31 (4.0%) of 781 hepatic resections. This complication carried high risks for surgical death (two patients [6.5%] died). The stepwise logistic regression analysis identified high-risk surgical procedure, in which the cut surface exposed the major Glisson’s sheath and included the hepatic hilum (i.e., anterior segmentectomy, central bisegmentectomy, or total caudate lobectomy), as the independent predictor of the development of postoperative bile leakage. None of the 102 cases in which an intraoperative bile leakage test was performed were subsequently complicated by postoperative bile leakage, and the preventive effect of the test was statistically significant. Patients with fisterographically demonstrable leakage from the hepatic hilum and with postoperative uncontrollable ascites had poor outcomes. ConclusionPatients with bile leakage from the hepatic hilum and postoperative uncontrollable ascites tend to have a poor prognosis. Therefore, especially when a high-risk surgical procedure is performed in patients with liver cirrhosis, more careful surgical procedures and use of an intraoperative bile leakage test are recommended.

Percutaneous microwave coagulation therapy in liver tumors

Purpose: Percutaneous microwave coagulation therapy (PMCT) is an interventional alternative for inoperable malignant liver tumors. in this paper, we report the results of our 3-year experience of PMCT in order to establish suitable indications for this treatmentMaterial and Methods: We studied a total of 27 inoperable liver tumors in 24 patients. Histology of the tumors showed 20 hepatocellular carcinomas (HCCs) (13 well differentiated, 4 moderately differentiated, and 3 poorly differentiated) and 7 metastases. These tumors were treated by PMCT and were followed for 4–40 months (average 18 months). Under US guidance, the tumors were coagulated by microwaves emitted from an electrode. the changes of tumor size after PMCT were evaluated by CT. When the tumors disappeared or were reduced in size after treatment, PMCT was regarded as effective. Complications from PMCT were also evaluated. the patient survival rate was obtained by means of the Kaplan-Meier methodResults: in tumors of 30 mm or less, treatment r...

Histone deacetylase inhibitor trichostatin A induces cell-cycle arrest/apoptosis and hepatocyte differentiation in human hepatoma cells.

Remodeling of the chromatin template by inhibition of HDAC activities represents a potential transcriptional therapy for neoplastic disease. A number of HDAC inhibitors that modulate in vitro cell growth and differentiation have been developed. We analyzed the effects of TSA, a specific and potent HDAC inhibitor, on the human hepatoma cell lines HepG2 and Huh‐7. TSA increased levels of acetylated histones H3 and H4 in both HepG2 and Huh‐7. It inhibited cell proliferation in vitro and induced G0/G1 arrest in HepG2 and apoptosis in Huh‐7. Gene expression of liver‐specific functions and liver‐enriched transcription factors was upregulated by TSA. TSA upregulated the ammonia removal rate and the albumin synthesis rate of HepG2 and Huh‐7. Our results indicate that TSA can induce cell‐cycle arrest/apoptosis and hepatocyte differentiation in human liver cancer cell lines.

Preoperative neutrophil-to-lymphocyte ratio is a predictor of survival after hepatectomy for hepatocellular carcinoma: a retrospective analysis.

Objective: To clarify the prognostic value of the preoperative blood neutrophil-to-lymphocyte ratio (NLR) in patients undergoing hepatectomy for hepatocellular carcinoma (HCC). Background: Although a high NLR has been reported to be a predictor of poor survival in patients with various cancers, it has not been extensively examined in patients with HCC. Methods: This retrospective study enrolled 958 patients who underwent hepatectomy without preoperative therapy for HCC from 1996 to 2009. Clinicopathological parameters, including NLR, were evaluated to identify predictors of overall and recurrence-free survival after hepatectomy. Univariate and multivariate analyses were performed, using the Cox proportional hazards model. The best cutoff was determined with time-dependent receiver operating characteristic curve. To determine the mechanism of NLR elevation, immunohistological examination using CD163 staining was performed in 150 patients. Results: Univariate and multivariate analyses showed that NLR was an independent prognostic factor in overall and recurrence-free survival. The best cutoff of NLR was 2.81, and 238 of 958 patients (24.8%) had NLR of more than 2.81. The 5-year survival rate after hepatectomy was 72.9% in patients with NLR less than 2.81 and 51.5% in those with NLR 2.81 or more (P < 0.0001). CD163-positive cell counts were significantly higher in tumors in the group with NLR 2.81 or more than in the group with NLR less than 2.81 (P = 0.0004). Conclusions: Our results show that NLR is an independent predictor of survival after hepatectomy in patients with HCC. Accumulation of tumor-associated macrophages in the tumor is associated with a high NLR.

Assessment of graft fibrosis by transient elastography in patients with recurrent hepatitis C after living donor liver transplantation

Background. Transient elastography (FibroScan) is a simple and noninvasive method to assess liver fibrosis by measuring liver stiffness and therefore can be a promising tool to evaluate liver fibrosis and avoid liver biopsy. We prospectively assessed the performance of transient elastography in patients with recurrent hepatitis C virus after living donor liver transplantation, in comparison with the surrogate serum markers. Methods. Fifty-six patients with recurrent hepatitis C virus after living donor liver transplantation, who underwent both liver biopsy and transient elastography were included in this study. The grade of liver fibrosis (the Scheuer classification) obtained by biopsy was compared to liver stiffness measured by the transient elastography. Results. The fibrosis grades were as follows: F0, n=22; F1, n=13; F2, n=9; F3, n=7; and F4, n=5. Liver stiffness values ranged from 2.9 to 72.0 kPa. The optimal cutoff values were 8.8 kPa for F≥1, 9.9 kPa for F ≥2, 15.4 kPa for F≥3, and 26.5 kPa for F≥4. The area under the receiver operator characteristic curve for the diagnosis of fibrosis (F≥2) by transient elastography was 0.92, while that by hyaluronic acid, type 4 collagen, alanine aminotransferase, and the aspartate transaminase to platelets ratio index were 0.52, 0.62, 0.64, and 0.70, respectively. Conclusions. These data suggest that transient elastography is a simple, noninvasive and reliable tool to assess liver fibrosis in patients with recurrent hepatitis C virus after living donor liver transplantation.

Skeletal muscle area correlates with body surface area in healthy adults

Depletion of skeletal muscle mass (sarcopenia) predicts survival in patients with cancer or liver cirrhosis. Recently, many reports have used computed tomography (CT) to measure muscle area to define sarcopenia. However, the definition of sarcopenia using CT has not been fully determined. The aim of this study was to establish formulae to calculate the standard area of skeletal muscle.

Prognostic factors affecting survival at recurrence of hepatocellular carcinoma after living-donor liver transplantation: with special reference to neutrophil/lymphocyte ratio.

Background In living-donor liver transplantation (LDLT) for hepatocellular carcinoma (HCC), it is important to predict not only who may be susceptible to recurrence but also who may survive longer. The neutrophil/lymphocyte ratio (NLR) is useful to properly assess the patient without decreasing the long-term survival after LDLT. In this study, we investigated the relationship between NLR and prognosis of patients with recurrent HCC after LDLT. Methods In total, 167 LDLTs for HCC were enrolled in this study. Clinicopathologic factors for HCC recurrence after LDLT were investigated and prognostic factors were examined with respect to survival. Results The following factors were found to be significant in patients with HCC recurrence compared with the controls: &agr;-fetoprotein ≧300 ng/mL, des-&ggr;-carboxyprothrombin ≧300 mAU/mL, NLR ≧4, tumor number >3, tumor size ≧5 cm, duration of last treatment of HCC to LDLT <3 months, Milan criteria exceeded, histologic tumor number ≧10, histologic tumor size >5 cm, poor differentiation, presence of histologic vascular invasion, adjuvant chemotherapy, and interferon therapy against patients with hepatitis C virus. Male sex, interferon therapy against patients with hepatitis C virus, &agr;-fetoprotein ≧300 ng/mL at recurrence, NLR ≧4 at recurrence, and nonsurgical resection for recurrent HCC were significantly related to poor prognosis. The 3-year survival rate after recurrence was 0% in patients with NLR ≧4 and 43.6% in patients with NLR <4. NLR was reelevated after LDLT in patients who later died; however, NLR gradually decreased in surviving patients. Conclusion NLR at recurrence is a prognostic factor affecting survival after recurrence in LDLT for HCC.

Strategies for Successful Left-Lobe Living Donor Liver Transplantation in 250 Consecutive Adult Cases in a Single Center

BACKGROUND Living donor liver transplantation (LDLT) using left-lobe grafts was not generally recognized as feasible due to the problem of graft size. STUDY DESIGN We retrospectively evaluated strategies for successful left-lobe LDLT in 250 consecutive cases stratified into 2 eras: Era 1 (n = 121), in which surgical procedures were continually refined, and Era 2 (n = 129), in which established procedures were used. RESULTS Graft volume (GV) did not affect the incidence of graft function or survival. Era 2 patients had decreased portal vein (PV) pressure at closure (16.0 ± 3.5 mmHg vs 19.1 ± 4.6 mmHg, p < 0.01), increased PV flow/GV (301 ± 125 mL/min/100g vs 391 ± 142 mL/min/100g, p < 0.01), and improved graft survival rate (1-year: 90.6% vs 81.8%. p < 0.01) despite the smaller GV/standard volume (SLV) ratio (36.2% ± 5.2% vs 41.2% ± 8.8%, p < 0.01) compared with Era 1. Patients in Era 2 had lower PV pressure and greater PV flow (y = 598-5.7 x, p = 0.02) at any GV/SLV compared with cases in Era 1 (y = 480-4.3 x, p < 0.01), representing greater graft compliance. Univariate analysis for graft survival showed that Era 1, Model for End-Stage Liver Disease (MELD) score ≥ 20, inpatient status, closing portal venous pressure ≥ 20 mmHg, no splenectomy, and operative blood loss ≥ 10 L were the risk factors for graft loss, and multivariate analysis showed that Era 1 was the only significant factor (p < 0.01). During Era 2, development of primary graft dysfunction was associated with inpatient recipient status (p = 0.02) and donor age ≥ 45 years (p < 0.01). CONCLUSIONS The outcomes of left-lobe LDLT were improved by accumulated experience and technical developments.

Prognostic impact of programmed cell death 1 ligand 1 expression in human leukocyte antigen class I-positive hepatocellular carcinoma after curative hepatectomy

AbstractBackground Hepatocellular carcinoma (HCC) is one of the most common solid tumors worldwide. Surgery is potentially curative, but high recurrence rates worsen patient prognosis. The interaction between the proteins programmed cell death 1 (PD-1) and programmed cell death 1 ligand 1 (PD-L1) is an important immune checkpoint. The significance of PD-L1 expression and human leukocyte antigen class I (HLA class I), recognized by CD8 T cells, in the prognosis of patients with HCC remains to be determined.MethodsWe assessed the levels of PD-L1 and HLA class I expression on HCC samples from 80 patients who had undergone hepatectomy at our institution, and evaluated the correlations between PD-L1 and HLA class I expression and patient prognosis.ResultsHigh HLA class I expression was correlated with significantly better recurrence-free survival (RFS), but not overall survival (OS). Multivariate analysis showed that high HLA class I expression was an independent predictor of improved RFS. Low expression of PD-L1 on HCC tended to predict better OS, but the difference was not statistically significant. PD-L1 expression on HCC correlated with the number of CD163-positive macrophages and HLA class I expression with CD3-positive cell infiltration. Univariable and multivariable analyses showed that combined PD-L1 low/HLA class I high expression on HCCs was prognostic for improved OS and RFS.ConclusionsPD-L1 status may be a good predictor of prognosis in HCC patients with high HLA class I expression. Novel therapies targeting the PD-L1/PD-1 pathway may improve the prognosis of patients with HCC.

Long-term favorable surgical results of laparoscopic hepatic resection for hepatocellular carcinoma in patients with cirrhosis: a single-center experience over a 10-year period.

BACKGROUND We first performed laparoscopic hepatic resection (Lap-Hx) for hepatocellular carcinoma (HCC) in 1994. Here we review the long-term surgical results of Lap-Hx for HCC in patients with cirrhosis over a 10-year period at a single institution. STUDY DESIGN Between January 2000 and December 2013, 99 patients with cirrhosis underwent open hepatic resection (Open-Hx) and 63 underwent Lap-Hx for primary HCC within the Milan criteria. We compared the operative outcomes and patient survival between the 2 groups. RESULTS There were no significant differences regarding patient background characteristics or tumor-related factors between the 2 groups. The morbidity rate of the Lap-Hx group was significantly lower than that of the Open-Hx group (26% vs 10%; p = 0.0459), and the complication rate of ascites was significantly lower (7% vs 0%; p = 0.0077). The mean duration of hospital stay of the Lap-Hx group was significantly shorter than that of the Open-Hx group (16 vs 10 days; p = 0.0008). There were no significant between-group differences regarding overall or disease-free survival. CONCLUSIONS Laparoscopic-Hx for HCC in patients with cirrhosis is associated with less morbidity and shorter hospital stays, with no compromise in patient survival. It may be time to consider changing the standard operation for primary HCC within the Milan criteria to Lap-Hx in patients with cirrhosis.