Toshiyuki Itamoto

Biliary Complications after Duct-to-duct Biliary Reconstruction in Living-donor Liver Transplantation: Causes and Treatment

BackgroundIn living-donor liver transplantation (LDLT), biliary complications are recognized as a significant cause of post-transplantation morbidity.MethodsEighty patients who underwent LDLT with duct-to-duct biliary reconstruction at Hiroshima University Hospital were enrolled in this study. The mean follow-up was 24 months (range, 3–72 months). Eighteen patients underwent the basiliximab-based immunosuppressive therapy, and 62 patients underwent non-basiliximab-based immunosuppressive therapy. The development of biliary complications after LDLT was retrospectively analyzed. Biliary complications were initially treated by endoscopic or radiological modalities.ResultsBiliary leakages and strictures occurred in 12 (15%) and 20 (25%) of the 80 patients, respectively. Stepwise multivariate analysis demonstrated bile leakage to be an independent risk factor for the development of biliary stricture (p = 0.001) and basiliximab-based immunosuppressive therapy to be an independent protective factor for postoperative biliary leakage (p = 0.005). The 1-week total doses of steroids were significantly lower in the basiliximab-based immunosuppressive regimes (mean dose: 573mg) than in the non-basiliximab-based ones (mean dose: 1,121mg) (p = 0.01). All patients with biliary leakage were successfully treated with endoscopic or radiological modalities, except one patient who was treated by surgical treatment. Endoscopic or radiological modalities were successful as primary treatment modalities in 12 (60%) of 20 patients with biliary strictures. Lastly, six patients were treated surgically with long-term success, except for one patient with chronic cholangitis who died after 16 months.ConclusionsSteroid-sparing basiliximab-based immunosuppressive therapy reduced the incidence of biliary leakage, and biliary leakage was the independent factor for biliary stricture. The non-surgical and surgical treatments for biliary complications were satisfactory.

Low incidence of acute rejection after living-donor liver transplantation: immunologic analyses by mixed lymphocyte reaction using a carboxyfluorescein diacetate succinimidyl ester labeling technique.

Background. To monitor antidonor alloreactivity for accurate diagnosis of acute rejection after living-donor liver transplantation (LDLT), we used a mixed lymphocyte reaction (MLR) assay using an intracellular fluorescent dye carboxyfluorescein diacetate succimidyl ester (CFSE)-labeling technique (CFSE-MLR) in 29 consecutive patients who underwent adult-to-adult LDLT. Methods. For patients who developed moderate or severe disorders in liver function, CFSE-MLR was performed together with needle biopsy of the liver allografts immediately after liver dysfunction had occurred. CFSE-labeled peripheral blood mononuclear cells (PBMC) from recipients and irradiated autologous, donor, or third-party PBMC were cultured, and then proliferation and CD25 expression in each of the CD4+ and CD8+ T cell subsets were analyzed by flow cytometry. Results. Twelve (41.4%) of the 29 patients developed moderate or severe disorders in liver function within 6 months after LDLT. Eight of the 12 patients (overall incidence of 27.6%) suffering from liver function disorder were diagnosed on the basis of liver biopsy results as having mild or moderate acute rejection. However, only 4 of the 12 patients (overall incidence of 13.8%) showed remarkable proliferation of CD8+ T cells in association with CD25 expression on antidonor CFSE-MLR. The other eight patients were eventually diagnosed as having recurrence of original hepatitis, drug-induced hepatotoxicity, or congestion of the anterior segment of the liver allograft by further extensive examinations or in retrospect. Conclusions. The results of CFSE-MLR assays, which could be used for rigorously monitoring rejection, provided evidence of low incidence of acute rejection after LDLT.

Autologous blood storage before hepatectomy for hepatocellular carcinoma with underlying liver disease

Preoperative autologous blood donation has been suggested for patients with liver disease who are to undergo liver resection. The aim of this retrospective study was to clarify the risk factors for increased blood loss and the need for blood transfusion during hepatectomy for hepatocellular carcinoma (HCC).

Clinicopathological features of elderly patients with hepatitis C virus-related hepatocellular carcinoma

BackgroundIt is well known that the incidence of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV) correlates with progression of liver fibrosis. However, there is little information on the impact of aging on hepatocarcinogenesis. The aim of this study was to elucidate the clinicopathological features of elderly patients with HCV-related HCC.MethodsThe study subjects were 693 consecutive patients newly diagnosed with HCC with anti-HCV. First, we divided them into a younger group (<70 years) and an elderly group (≥70 years) and compared clinicopathological features between the two groups. Next, we selected pure HCV-related HCC patients by excluding the patients with other probable factors for hepatocarcinogenesis (anti-HBc, interferon therapy, and alcohol) and compared the two groups again.ResultsHigher platelet count, lower male/female ratio, lower rate of habitual alcohol consumption, and better Child-Pugh class were recognized in the elderly group thant the younger group, statistically. In 133 cases of hepatic resection, fibrosis stage was lower in the elderly than the younger group. After selection of pure HCV-related HCC patients, in a stepwise multi variate analysis, male sex and platelet count <10 × 104/mm3 were significant variables associated with age <70. Regarding the latency period to HCC development, the patients who received a blood transfusion at an older age developed HCC sooner despite their lower grade of fibrosis.ConclusionsThe elderly patients developed HCC more often, despite their lower grade of fibrosis, compared with the younger patients. In addition to fibrosis, aging could be a factor affecting HCV-related hepatocarcinogenesis.

Safety of donor right hepatectomy for adult-to-adult living donor liver transplantation.

The purpose of this study was to ascertain the usefulness of preoperative evaluations of donors by computed tomography (CT) volumetry and CT cholangiography for prevention of unexpected liver failure and biliary complications after donor right hepatectomy for adult‐to‐adult living donor liver transplantation. Fifty‐two donors who underwent right hepatectomy without the middle hepatic vein were enrolled in this study. The values of graft weight (GW) were significantly correlated with those of estimated graft volume (GV; P < 0.0001). GW was predicted by the following formula: GW = 155.25 + 0.658 × GV; r2 = 0.489. CT cholangiography revealed anatomical variants of biliary structure in one‐third of the donors and also clearly showed one or two small biliary branches from the caudate lobe to the right hepatic ducts or the confluence in 58% of the donors. Biliary leakage, which was treated by conservative therapy, occurred in only one donor (1.9%). No donors received homologous blood transfusion. Hyperbilirubinemia (serum total bilirubin >5 mg/dl) occurred in 5.8% of the donors during their early postoperative periods. Precise evaluations of liver remnant volume by CT volumetry and biliary variation by CT cholangiography are essential for performing safe donor hepatectomy, preventing hepatic insufficiency and minimizing the risk of biliary tract complications.

Single-port laparoscopic colectomy versus conventional laparoscopic colectomy for colon cancer: a comparison of surgical results

BackgroundSingle-port laparoscopic surgery is a new technique that leaves no visible scar. This new technique has generated strong interest among surgeons worldwide. However, single-port laparoscopic colon surgery has not yet been standardized. Our aim in this study was to evaluate the feasibility of single-port laparoscopic colectomy compared with conventional laparoscopic colectomy for colon cancer.MethodsWe conducted a case-matched, controlled study comparing single-port laparoscopic colectomy to conventional laparoscopic colectomy for right-sided colon cancer.ResultsA total of ten patients were included for the single-port laparoscopic colectomy (S-LAC) group and ten patients for the conventional laparoscopic colectomy (C-LAC) group. The length of the skin incision in the S-LAC group was significantly shorter than that of the C-LAC group.ConclusionOur early experiences indicated that S-LAC for right-sided colon cancer is a feasible and safe procedure and that S-LAC results in a better cosmetic outcome.

Morphological and microarray analyses of human hepatocytes from xenogeneic host livers.

We previously produced mice with human hepatocyte (h-hep) chimeric livers by transplanting h-heps into albumin enhancer/promoter-driven urokinase-type plasminogen activator-transgenic severe combined immunodeficient (SCID) mice with liver disease. The chimeric livers were constructed with h-heps, mouse hepatocytes, and mouse hepatic sinusoidal cells (m-HSCs). Here, we investigated the morphological features of the chimeric livers and the h-hep gene expression profiles in the xenogeneic animal body. To do so, we performed immunohistochemistry, morphometric analyses, and electron microscopic observations on chimeric mouse livers, and used microarray analyses to compare gene expression patterns in hepatocytes derived from chimeric mouse hepatocytes (c-heps) and h-heps. Morphometric analysis revealed that the ratio of hepatocytes to m-HSCs in the chimeric mouse livers were twofold higher than those in the SCID mouse livers, corresponding to twin-cell plates in the chimeric mouse liver. The h-heps in the chimeric mouse did not show hypoxia even in the twin-cell plate structure, probably because of low oxygen consumption by the h-heps relative to the mouse hepatocytes (m-heps). Immunohistochemical and electron microscopic examinations revealed that the sinusoids in the chimeric mouse livers were normally constructed with h-heps and m-HSCs. However, a number of microvilli projected into the intercellular clefts on the lateral aspects of the hepatocytes, features typical of a growth phase. Microarray profiles indicated that ∼82% of 16 605 probes were within a twofold range difference between h-heps and c-heps. Cluster and principal component analyses showed that the gene expression patterns of c-heps were extremely similar to those of h-heps. In conclusion, the chimeric mouse livers were normally reconstructed with h-heps and m-HSCs, and expressed most human genes at levels similar to those in human livers, although the chimeric livers showed morphological characteristics typical of growth.

Scientific assessment of endoscopic surgical skills.

Abstract Recently, significant attention has been focused on training and education for safe endoscopic surgery. A new assessment method, the Hiroshima University Endoscopic Surgical Assessment Device (HUESAD), has been designed at Hiroshima University to evaluate the smoothness of the movement of endoscopic instruments from velocity. Experts (with experience in performing more than 100 laparoscopic surgeries) and novices (with no experience in performing laparoscopic surgery) were recruited for this study. The aim of task 1 was to move the tip of the endoscopic instrument on the tops of poles from A to C, and task 2 was to move it from the right pole B to the left pole D. The peak velocity (Vp) and the time when peak velocity appears (Tp) were analyzed. Both the peak velocity (Vp) and the time when peak velocity appears (Tp) to perform task 1 and task 2 were significantly faster in the expert group than in the novice group. The peak velocity (Vp) and the time when peak velocity appears (Tp) in HUESAD, which indicate the smoothnes of the endoscopic procedure, are among the most important factors for assessing endoscopic surgical skills.

GH enhances proliferation of human hepatocytes grafted into immunodeficient mice with damaged liver

We investigated effects of human (h) GH on the proliferation of h-hepatocytes that had been engrafted in the liver of albumin enhancer/promoter driven-urokinase plasminogen activator transgenic/severe combined immunodeficiency disease (uPA/SCID) mice (chimeric mice). The h-hepatocytes therein were considered to be deficient in GH, because hGH receptor (hGHR) is unresponsive to mouse GH. Actually, hIGF-1 was undetectable in chimeric mouse sera. The uPA/SCID mice were transplanted with h-hepatocytes from a 6-year (6Y)-old donor, and were injected with recombinant hGH (rhGH). rhGH stimulated the repopulation speed of h-hepatocytes; and up-regulated hIGF-1, human signal transducers and activators of transcription (hSTAT) 3, and cell cycle regulatory genes such as human forkhead box M1, human cell division cycle 25A, and human cyclin D1. To confirm the reproducibility of these effects of rhGH, similar experiments were run using h-hepatocytes from a 46-year (46Y)-old donor. rhGH similarly enhanced their repopulation speed and up-regulated the expression of the above-tested genes, especially hIGF-1 and hSTAT1. The extent of the enhancement by rhGH was much less than that in 6Y-hepatocyte-chimeric mice most probably due to the difference in GHR expression levels between the two donors. In conclusion, this study clearly demonstrated that rhGH stimulates the proliferation of h-hepatocytes in vivo.

Hepatocyte growth factor prevents chronic allograft dysfunction in liver-transplanted rats.

Background. Hepatocyte growth factor (HGF) is a growth factor with multiple biologic properties, including mitogenic, morphogenic, anti-apoptotic, and antifibrogenic activities. Long-term administration of the deletion variant of HGF (dHGF) might contribute to the prevention of chronic liver allograft dysfunction, which is attributed to immunologic and nonimmunologic reactions. Methods. Low-dose tacrolimus was administered to rat-liver recipients after transplantation. Effects of dHGF on transplanted livers treated with low-dose tacrolimus were investigated. Results. Rats receiving liver transplants treated with only low-dose tacrolimus administration showed chronic allograft dysfunction. Treatment with dHGF prolonged the survival time of rats that received liver allografts and suppressed fibrosis of liver allograft. Treatment with dHGF also suppressed the expression levels of interleukin (IL)-1&bgr;, caspase-1, and transforming growth factor (TGF)-&bgr; mRNAs in liver allografts. Conclusions. The findings indicate that dHGF may prevent chronic liver-allograft dysfunction and thus may become a novel treatment for chronic liver-allograft dysfunction.