Masayoshi Ijichi

Fluorescent cholangiography illuminating the biliary tree during laparoscopic cholecystectomy

Although intraoperative cholangiography has been recommended for avoiding bile duct injury during laparoscopic cholecystectomy, radiographic cholangiography is time consuming and may itself cause injury to the bile duct. Recently, a novel fluorescent cholangiography technique using the intravenous injection of indocyanine green (ICG) has been developed.

A comparative study of postoperative complications after hepatectomy in patients with and without chronic liver disease

BACKGROUND Although hepatic resection is the most reliable treatment for hepatocellular carcinoma, impaired liver function because of cirrhosis or chronic hepatitis contributes to relatively high rates of postoperative complications. We have reviewed a series of hepatectomies at our institution and investigated risk factors for complications after hepatectomy in patients with impaired liver compared with patients with normal liver. METHODS From October 1994 to March 1998, 277 hepatectomies for hepatocellular carcinoma, cholangiocellular carcinoma, metastatic liver tumors, and other hepatic diseases were performed. In an attempt to clarify the safety of hepatectomy for the impaired liver at our institution, we did a comparative study of postoperative complications after hepatectomy in 2 groups: patients with impaired livers (187 hepatectomies) and patients with normal livers (90 hepatectomies). RESULTS Of the 277 hepatectomies, bile leakage occurred in 25 patients (16 in impaired livers vs 9 in normal livers), abdominal infection in 45 patients (30 vs 15 patients), wound infection in 13 patients (9 vs 4 patients), pleural effusion in 52 patients (35 vs 17 patients), atelectasis in 26 patients (17 vs 9 patients), pneumonia in 4 patients (3 vs 1 patients), ileus in 6 patients (3 vs 3 patients), intra-abdominal hemorrhage in 3 patients (0 vs 3 patients), and hyperbilirubinemia in 5 patients (4 vs 1 patients). Hepatic insufficiency and hospital death were not experienced in this series. The mean postoperative hospital stay was 22.9 days (23.5 vs 23.1 days), and except for intra-abdominal hemorrhage there was no statistically significant difference between the 2 groups. CONCLUSIONS Hepatectomy for the impaired liver is now as safe a procedure as for the normal liver, provided the overall guidelines outlined in our algorithm are followed.

Uracil‐tegafur as an adjuvant for hepatocellular carcinoma: A randomized trial

Frequent recurrence of hepatocellular carcinoma (HCC) after surgery remains a major clinical problem. This randomized controlled trial evaluated whether postoperative adjuvant therapy with oral uracil‐tegafur (UFT) prevents recurrence of HCC. A total of 160 patients who underwent curative hepatic resection for HCC were randomly assigned to receive either 300 mg/day of UFT for 1 year after surgery (n = 79, UFT group) or surgery alone (n = 80, control group). The primary endpoint was recurrence‐free survival, and the secondary endpoint was overall survival. Other study variables included liver function and type of recurrence. During a median follow‐up of 4.8 years (range: 0.5‐7.9), recurrence‐free survival curves in the groups were similar (P = .87). Overall survival was slightly but not significantly worse in the UFT group than in the control group (P = .08). The rates of recurrence‐free and overall survival at 5 years were 29% and 58%, respectively, in the UFT group, as compared with 29% and 73%, respectively, in the control group. The hazard ratio for recurrence in the UFT group, relative to the control, was 1.01 (95% confidence interval: 0.84‐1.22, P = .87). The proportion of patients with advanced recurrence (i.e., multiple, extrahepatic, or associated with vascular invasion) was significantly higher in the UFT group (74%, 43 of 58 patients with recurrence) than in the control group (53%, 30 of 57) (P = .02). In conclusion, our results offer no evidence to support potential benefits of adjuvant chemotherapy with UFT after surgery in patients with HCC and suggest that such treatment may even worsen overall survival. (HEPATOLOGY 2006;44:891–895.)

Indocyanine green‐fluorescent imaging of hepatocellular carcinoma during laparoscopic hepatectomy: An initial experience

Introduction: Laparoscopic hepatectomy has disadvantages in intraoperative diagnosis, because it offers limited visualization and palpability of the liver surface. Recently, we developed a novel fluorescent imaging technique using indocyanine green (ICG), which would enable identification of liver cancers during open hepatectomy. However, this technique has not yet been applied to laparoscopic hepatectomy.

Effect of apolipoprotein E polymorphism on bile lipid composition and the formation of cholesterol gallstone.

OBJECTIVES:It remains a matter of controversy whether possession of the apolipoprotein E4 (apoE4) allele is a genetic risk factor for the formation of cholesterol gallstones. The aim of the present study was to test this hypothesis by investigating the effect of apoE4 on bile lipid composition in normal subjects and in patients with cholesterol gallstones and to evaluate the distributions of apoE alleles in these two groups.METHODS:The study population consisted of 79 patients who underwent open or laparoscopic cholecystectomy for symptomatic cholesterol gallstone disease. The control group (n = 53) included 11 patients with benign gallbladder polyps and 42 normal subjects acting as donors in living donor liver transplantation. The apoE genotypes were assessed by dot blot hybridization with digoxigenin-labeled probes. Bile lipid composition was determined by enzymatic assays and high performance liquid chromatography.RESULTS:Bile lipid composition and cholesterol saturation index (CSI) were similar in the control subjects harboring the apoE4 allele and those without apoE4 (mean CSI, 85.9% and 72.2%, respectively, p = 0.69). Likewise, in the cholesterol gallstone patients, bile lipid composition and CSI were similar in the patients with and without apoE4 allele (mean CSI, 134.9% vs 152.2%, p = 0.6). Furthermore, the prevalence of the apoE4 allele was similar in the patients with cholesterol gallstones and in the control group (8.5% vs 7.6%, p = 0.46, OR = 0.88; 95% CI = 0.64–1.22).CONCLUSION:The apoE4 allele is not a contributory factor to cholesterol gallstone formation, at least in the Japanese population.

Simple quantitative assay of alpha-fetoprotein mRNA in liver tissue using the real-time detection polymerase chain reaction assay - its application for clinical use.

Alpha-feto protein (AFP) mRNA levels increase in hepatocellular carcinoma (HCC) cells as compared with non-neoplastic tissue. Therefore, detection of AFP mRNA in blood nuclear cells is useful for the evaluation of treatment efficacy and prognosis of HCC. In this study, simple and reproducible methods were developed to quantify AFP mRNA using the real-time RT-PCR assay (Taq Man assay). By using in vitro synthesized AFP and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) RNA, the sensitivity and dynamic range of the RT-PCR assay were established. AFP mRNA in both HCC and non-neoplastic tissue, as well as in cell lines, were measured using this assay system. The expression of the AFP mRNA level was normalized using the GAPDH house keeping gene product as an endogenous reference. AFP and GAPDH mRNA can be quantified in the range of 10-10(8) copies when using this quantitative assay. Among HCC cell lines, Huh 7 and HepG2 cells, respectively, represented 1.5x10(6) and 6.0x10(5) AFP mRNA/10(6) GAPDH mRNA, in contrast to 6, 23 and 230 AFP mRNA/10(6) GAPDH mRNA for HLE, HLF and PLC/PRF/5 cells, respectively. Other cell lines derived from stomach, pancreas, and colon cancers have 10 AFP mRNA copies/10(6) GAPDH mRNA. In liver tissue from patients with chronic hepatitis, and the non-neoplastic portion of the liver from HCC patients, AFP mRNA distributes from 2.5x10(3) to 5.8x10(4)/10(6) GAPDH transcripts. In contrast, AFP mRNA in tumor cells were more than 100-fold higher than that found in corresponding non-neoplastic portions in two patients who had a high level of AFP in serum. The establishment of the TaqMan quantifying system for AFP mRNA may have important clinical implications.

Inclusion of tumor markers improves the correlation of the Milan criteria with vascular invasion and tumor cell differentiation in patients with hepatocellular carcinoma undergoing liver resection (#JGSU-D-07-00462).

The currently used criteria, such as the Milan criteria, to select a candidate of liver transplantation for HCC consists of size and number of tumors because vascular invasion and poor differentiation, the strongest prognostic factors, are difficult to be assessed preoperatively. We hypothesized that inclusion of two tumor markers (alpha-fetoprotein and des-γ-carboxy prothrombin) into the criteria would increase the prediction accuracy of these factors. Our hypothesis was tested in 478 HCC patients undergoing liver resection. The models with or without markers, constructed at predicting vascular invasion (n = 150) or poor differentiation (n = 49), were compared. The model including markers was superior at predicting the absence of vascular invasion to either the Milan criteria alone [at 81.2% sensitivity; specificity, 52.4 vs 43.3%; difference, 9.1%(95% CI, 1.3–14.2%)] or a model in which size and number varied freely [AUCs of receiver operating characteristic curves, 75.2 vs 69.1%; difference, 6.1%(2.33–10.7%)]. The model incorporating markers was also superior at predicting well to moderate differentiation to either the Milan criteria [at 74.5% sensitivity; specificity, 57.1 vs 38.8%; difference, 18.3%(2.4–32.7%)] or a model with size and number [AUCs, 71.5 vs 59.0%; difference, 12.5%(5.84–21.4%)]. In conclusion, the tumor marker levels should be considered when selecting patients with HCC for liver transplantation.

Venoplasty of recipient hepatic veins in living-related liver transplantation

LIVING-related liver transplantation (LRLT) produced encouraging results with more than an 80% 5-year patient survival rate. However, further efforts are needed to pursue better results. An important goal in hepatic venous reconstruction in LRLT using the piggyback method is to prevent outflow obstruction. We are adopting two types of venoplasty for recipient hepatic veins. One is venoplasty to make the common trunk using the middle and left hepatic veins for larger recipients; the other is venoplasty to make the common trunk using the right, middle, and left hepatic veins for smaller recipients. We present our hepatic venoplasty methods in recipients and their results.

Adjuvant Oral Uracil-Tegafur with Leucovorin for Colorectal Cancer Liver Metastases: A Randomized Controlled Trial

Background The high recurrence rate after surgery for colorectal cancer liver metastasis (CLM) remains a crucial problem. The aim of this trial was to evaluate the efficacy of adjuvant therapy with uracil-tegafur and leucovorin (UFT/LV). Methods In the multicenter, open-label, phase III trial, patients undergoing curative resection of CLM were randomly assigned in a 1:1 ratio to either the UFT/LV group or surgery alone group. The UFT/LV group orally received 5 cycles of adjuvant UFT/LV (UFT 300mg/m2 and LV 75mg/day for 28 days followed by a 7-day rest per cycle). The primary endpoint was recurrence-free survival (RFS). Secondary endpoints included overall survival (OS). Results Between February 2004 and December 2010, 180 patients (90 in each group) were enrolled into the study. Of these, 3 patients (2 in the UFT/LV group and 1 in the surgery alone group) were excluded from the efficacy analysis. Median follow-up was 4.76 (range, 0.15–9.84) years. The RFS rate at 3 years was higher in the UFT/LV group (38.6%, n = 88) than in the surgery alone group (32.3%, n = 89). The median RFS in the UFT/LV and surgery alone groups were 1.45 years and 0.70 years, respectively. UFT/LV significantly prolonged the RFS compared with surgery alone with the hazard ratio of 0.56 (95% confidence interval, 0.38–0.83; P = 0.003). The hazard ratio for death of the UFT/LV group against the surgery alone group was not significant (0.80; 95% confidence interval, 0.48–1.35; P = 0.409). Conclusion Adjuvant therapy with UFT/LV effectively prolongs RFS after hepatic resection for CLM and can be recommended as an alternative choice. Trial Registration UMIN Clinical Trials Registry C000000013

Resection of a methicillin-resistant Staphylococcus aureus liver abscess in a patient with Crohn's disease under infliximab treatment: a case report

IntroductionA liver abscess in Crohn’s disease is a rare but important entity that is associated with a poor prognosis and high mortality when treatment is delayed. We report a case of successful liver segmentectomy for a methicillin-resistant Staphylococcus aureus liver abscess in a patient with Crohn’s disease under infliximab treatment.Case presentationA 31-year-old Japanese man, who had been treated with infliximab infusions for Crohn’s disease, was referred to our hospital presenting with an abrupt onset of high fever and an elevated white blood cell count and serum C-reactive protein level. Computed tomography revealed a liver abscess occupying segment 8. The limited effect of percutaneous transhepatic abscess drainage and antibiotics led us to perform radical resection of the abscess. The patient recovered quickly after surgery and the postoperative course was uneventful.ConclusionThe present case suggests that surgical removal of an abscess should be considered for patients under immunosuppression or refractory to conventional treatment.