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Mitsuo Shimada

Publications and source records attributed to Mitsuo Shimada.

At least 19 recordsLinked to original sources

An Exosomal Signature for Preoperative Detection of Occult Liver Metastasis in Pancreatic Cancer.

IMPORTANCE: Early liver metastasis (early-LiM) after pancreatectomy represents an aggressive biological phenotype of pancreatic ductal adenocarcinoma (PDAC) and is associated with markedly poor survival. Reliable preoperative biomarkers to identify occult hepatic micrometastasis remain lacking. OBJECTIVE: To develop and externally validate a circulating exosomal microRNA (exo-miRNA)-based machine learning model for preoperative detection of occult early-LiM in PDAC. DESIGN, SETTING, AND PARTICIPANTS: This multicenter retrospective case-control study included 3 phases: genome-wide discovery using exo-miRNA sequencing (discovery cohort), model development (training cohort), and independent external validation (2 validation cohorts). The study took place at 4 medical centers in China, Japan, and South Korea. A total of 372 patients were enrolled between 2011 and 2024. Data were analyzed from July 2024 to November 2025. EXPOSURES: Circulating plasma-derived exosomal miRNA expression profiles. MAIN OUTCOMES AND MEASURES: The primary outcome was early-LiM, defined as liver recurrence within 6 months after curative-intent resection. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC) and survival outcomes were assessed using Kaplan-Meier analysis. RESULTS: Among 372 patients with PDAC (median [IQR] age, 67 [59-73] years; 229 [61.6%] male and 143 [38.4%] female; median follow-up among survivors, 969 days),early-LiM was associated with significantly worse overall survival compared with other recurrence patterns (median OS, 9.1 months vs 26.6-31.8 months; log-rank P&#x2009;<&#x2009;.001). A 7-exo-miRNA extreme gradient boosting model demonstrated discrimination in the training cohort (AUC, 0.899; 95% CI, 0.822-0.976) and maintained performance in external testing cohorts (AUC, 0.876; 95% CI, 0.846-0.951 and AUC, 0.862; 95% CI, 0.744-0.981). The exo-miRNA panel score remained an independent identifier of early-LiM in multivariable analysis (odds ratio, 26.49; 95% CI, 18.45-55.28; P&#x2009;<&#x2009;.001) and stratified overall survival (log-rank P&#x2009;<&#x2009;.001). Decision curve analysis suggested improved net clinical benefit compared with conventional clinicopathologic variables. CONCLUSION AND RELEVANCE: In this multicenter study, a circulating exo-miRNA-based machine learning model enabled preoperative detection of occult early liver metastasis risk in PDAC. These findings support the potential of exosomal biomarkers to inform biology-guided treatment sequencing and warrant prospective validation.

Journal Article↗

Critical roles of memory T cells and antidonor immunoglobulin in rejection of allogeneic bone marrow cells in sensitized recipient mice.

BACKGROUND: Allosensitization is a major risk factor for graft failure in clinical bone marrow transplantation, even with an human leukocyte antigen (HLA)-matched combination under radiation-based conditioning regimens. The critical components of immunological memory in donor bone marrow graft rejection in allosensitized hosts remain unclear at present. METHODS: C57BL/6-recipient mice, which had been intraperitoneally injected with splenocytes from donor C3H mice on day -35 (sensitized recipients), had been lethally irradiated with 10-Gy whole-body irradiation and were intravenously injected with T-cell-depleted bone marrow cells (TCD-BMC) from C3H mice or third-party SJL mice. RESULTS: Lethally irradiated recipient mice, which had been sensitized by donor splenocytes 5 weeks before the transplantation of TCD-BMC, completely rejected the donor-BMC in a donor-specific manner, whereas none of the nonsensitized recipient mice, all of which showed full allogeneic chimerism, rejected the donor TCD-BMC. Antibody-mediated T cell and/or Natural Killer (NK) cell depletion did not improve the ability of the sensitized recipients to overcome the rejection even when a megadose of TCD-BMC was administered to the sensitized recipients. Furthermore, BMC rejection occurred in sensitized B cell-deficient mice. In adoptive transfer experiments, naive mice, which received a transfer of purified T cells from sensitized mice, rejected the donor BMC, but not those from nonsensitized mice. Moreover, naive mice, which received a transfer of serum containing antidonor immunoglobulin, rejected the donor BMC. CONCLUSIONS: These findings suggest that alloreactive memory T cells and antidonor immunoglobulin independently function to reject donor BMC in sensitized recipients.

Adoptive Transfer↗

Combination therapy of human pancreatic cancer implanted in nude mice by oral fluoropyrimidine anticancer agent (S-1) with interferon-alpha.

PURPOSE: We evaluated the antitumor and antiangiogenic activities of human natural interferon-alpha (IFN-alpha) alone or in combination with S-1 against human pancreatic cancer cells. METHODS: Three days after the subcutaneous (s.c.) implantation of tumor cells, mice (n = 12) were received s.c. injection with IFN-alpha alone (10,000 U six times a week), oral administration with S-1 alone (8 mg/kg six times a week), or both with IFN-alpha and S-1 (8, 10, 12 mg/kg six times a week). RESULTS: Administration of IFN-alpha in combination with S-1 significantly decreased progressive growth and angiogenesis of human pancreatic cancer cells. The combination therapy produced more significant inhibition in expression of the representative proangiogenic molecules, vascular endothelial growth factor and basic fibroblast growth factor than individual treatment either IFN-alpha or S-1 alone did. These treatments also decreased the staining of proliferating cell nuclear antigen, induced apoptosis and decreased microvessel density. In order to better understand the precise molecular mechanisms by which IFN-alpha and S-1 exert its effects, we have utilized cDNA microarray including 124 known genes to determine the gene expression profile altered by IFN-alpha and S-1 treatment. We found a total of seven genes which showed a twofold change after IFN-alpha and S-1 treatment in addition to VEGF, bFGF, CD31, MMP-2, MMP-7 and MMP-9. Among these genes, we found down-regulation of six genes and up-regulation of one gene, which are related to angiogenesis, tumor cell invasion and metastasis. CONCLUSIONS: These data suggest that administration of IFN-alpha in combination with S-1 may provide a novel and effective approach to the treatment of human pancreatic cancer.

Angiogenesis Inhibitors↗

Specific peptide ligand for Grb7 signal transduction protein and pancreatic cancer metastasis.

BACKGROUND: Pancreatic cancer is one of the most aggressive malignancies, with high rates of invasion and metastasis and with generally poor prognosis. We previously found that metastasis was strongly associated with the expression of growth factor receptor-bound protein 7 (Grb7), which contains a Src homology 2 (SH2) domain. In this study, we evaluated Grb7 protein as a molecular target of therapy for metastatic pancreatic cancer. METHODS: Grb7 protein expression was measured by immunohistochemistry in 36 human pancreatic cancer specimens and adjacent normal pancreatic tissue. We synthesized a nonphosphorylated peptide inhibitor that binds specifically to the SH2 domain of Grb7. Intracellular signaling was assessed by immunoprecipitation and immunoblot assays in cultured human pancreatic cancer cells. Cell migration was measured with a modified Boyden chamber method. Peritoneal metastasis of the pancreatic cancer cells was measured with a mouse model. All statistical tests were two-sided. RESULTS: We found that 22 (61%) of 36 pancreatic cancer specimens had higher levels of Grb7 protein than their corresponding normal pancreatic tissue specimens. Grb7 expression was statistically significantly different between specimens from patients without lymph node metastasis (stage N0; two of the 10 patients) and patients with lymph node metastasis (stages N1 + N2; 20 of the 26 patients) (P = .006). The Grb7 peptide inhibitor selectively blocked the interaction between Grb7 and focal adhesion kinase and blocked the phosphorylation of Grb7 protein. In vivo Grb7 peptide inhibitor statistically significantly attenuated cell migration (for control peptide, 87.5 cells migrated, 95% confidence interval [CI] = 82.6 to 92.4 cells; for Grb7 peptide, 5.7 cells migrated, 95% CI = 2.3 to 9.0 cells; P < .001) and peritoneal metastasis of the pancreatic cancer cells in a mouse model, as assessed by the number of nodules (control = 72.6 nodules, 95% CI = 55.8 to 89.4 nodules; and for Grb7 peptide = 3.2 nodules, 95% CI = 1.6 to 4.8 nodules; P < .001, t test) and their weight (control = 4.13 g, 95% CI = 3.40 to 4.86 g; Grb7 peptide = 0.19 g, 95% CI = 0.06 to 0.32 g; P < .001, t test). CONCLUSIONS: The Grb7 peptide inhibitor appears to be a promising molecularly targeted therapeutic agent against metastatic pancreatic cancer.

Adenocarcinoma↗

Hyperbaric oxygen induces vascular endothelial growth factor and reduces liver injury in regenerating rat liver after partial hepatectomy.

BACKGROUND/AIMS: The aim of this study was to investigate the effect and the mechanism of hyperbaric oxygen treatment on regenerating rat liver after partial hepatectomy (PH). METHODS: Wistar rats underwent a 70% PH, followed by treatment with hyperbaric oxygen starting 8 h after PH. The regenerated liver weight and serum parameters were compared. Proliferation of both hepatocytes and sinusoidal endothelial cell (SEC) was also monitored by evaluating the proliferating cell nuclear antigen (PCNA) labeling index. Furthermore, the hepatic adenosine triphosphate levels and vascular endothelial growth factor (VEGF) protein expression were analyzed at different times. RESULTS: Hyperbaric oxygen treatment significantly reduced the serum alanine aminotransferase levels at 24 h, total bilirubin and total bile acid levels at 48 and 72 h, respectively. No significant differences in the hepatic adenosine triphosphate levels, the restitution of liver weight, or PCNA positive hepatocytes were observed between the two groups. The PCNA positive SEC, in contrast, was significantly increased in the hyperbaric oxygen group at 48h, furthermore, the hyperbaric oxygen treatment significantly increased the expression of VEGF protein in the regenerating liver at 24 and 48 h. CONCLUSIONS: Hyperbaric oxygen treatment can be considered as a therapeutic modality after massive PH.

Adenosine Triphosphate↗

Auxiliary partial orthotopic living donor liver transplantation for a child with congenital absence of the portal vein.

Congenital absence of the portal vein (CAPV) is a rare malformation of the mesenteric vasculature in which visceral venous blood bypasses the liver, completely draining into the systemic circulation through a congenital porto-systemic shunt. Liver transplantation has rarely been indicated for patients with this disease. We present a child with CAPV who was managed successfully by living donor auxiliary partial orthotopic liver transplantation (APOLT), while preserving the right lobe of the native liver. In conclusion, APOLT for patients with CAPV is a feasible and ideal procedure because portal vein (PV) diversion is not necessary.

Child, Preschool↗

Biliary strictures in living donor liver transplantation: incidence, management, and technical evolution.

Biliary complications, biliary strictures (BS) in particular, continue to be a significant cause of morbidity after LDLT despite technical refinement. In this study, we assessed the incidence of BS and their management in living donor liver transplantation (LDLT) with special reference to the type of biliary reconstruction. A total of 182 LDLTs performed at our institution for either adult (n = 157) or pediatric (n = 25) patients were included in the study. The duct-to-duct (DD) biliary reconstruction was performed for 106 cases, while the conventional Roux-en-Y hepaticojejunostomy (HJ) was utilized for the remaining 76 cases. Overall, BS developed in 46/182 (25.3%) of the cases (DD, 26.4%; HJ, 25.0%). The 1- and 3-year cumulative incidences of BS were 22.9% and 31.9%, respectively, in the DD group, and 15.2% and 29.1%, respectively, in the HJ group (P= not significant). The left-lobe LDLT was more prone to develop BS. Continuous anastomosis tended to be associated with the high incidence of BS in the DD group. The incidence of anastomotic leak was significantly lower in the DD group. Intervention via either pre-cutaneous or endoscopic approach was successful in the majority of cases, although recurrence could occur in some patients. In conclusion, BS was not associated with the type of reconstruction in LDLT. The primary radiological or endoscopic interventions were satisfactory treatments of choice. Technical refinement is an important factor to reduce the incidence of BS.

Adult↗

Reconstruction of the middle hepatic vein tributaries using the recipient's recanalized umbilical vein in right-lobe living-donor liver transplantation.

BACKGROUND: Right-lobe grafts without the middle hepatic vein (MHV) can cause severe congestion of the anterior segment in living-donor liver transplantation (LDLT). However, the indications and methods for reconstructing the MHV or its tributaries remain controversial. METHODS: We herein describe two cases of the successful use of the recipient's recanalized umbilical vein as an interposition graft to drain the major MHV tributaries in right-lobe LDLTs. RESULTS: After surgery, both right-lobe grafts are currently functioning well and all of the reconstructed venous tributaries have been confirmed to be patent by doppler ultrasonography. The histopathological features of the recanalized umbilical vein showed an intact intima with thickened media. CONCLUSIONS: The use of the recipient's recanalized umbilical vein is a good option for reconstructing MHV tributaries in right-lobe LDLTs.

Hepatic Veins↗

Clinical roles of increased populations of Foxp3+CD4+ T cells in peripheral blood from advanced pancreatic cancer patients.

OBJECTIVES: Further metastasis should be avoided in pancreatic cancer (PC) patients for effective surgical treatment. Regulatory T cells (Foxp3CD4 T cells including CD4CD25 T cells and CD4CD25 T cells) play important roles in tumor immunity. This study aimed to investigate whether regulatory T cells participate in metastasis. METHODS: Peripheral blood was withdrawn from PC patients, as well as healthy volunteer donors as controls. The peripheral blood mononuclear cells (PBMCs) were subjected to FACScan analysis after labeling with anti-CD4, anti-CD25, and anti-Foxp3 antibodies. Tumor markers, including DUPAN2 and CA19-9, surface markers, such as the CD4/CD8 ratio, and the CD57 cell population were assessed. Clinical stages were classified according to the TNM classification. RESULTS: The Foxp3CD4 T-cell population among the PBMCs was significantly increased in PC patients (8.10% +/- 4.65%) compared with healthy donors (2.47 +/- 0.78%) (P < 0.001). No significant relationships existed for the tumor markers, CD4/CD8 ratio, and CD57 cells. However, a significant correlation was found between Foxp3CD4 T cells among the PBMCs and the TNM stage (P < 0.05). CONCLUSIONS: Foxp3CD4 T cells are good markers for metastasis detection in PC patients and more accurate than other conventional tumor markers, especially at advanced stages of the disease.

Aged↗

Effect of hyperbaric oxygen on cold storage of the liver in rats.

BACKGROUND: The depletion of biochemical energy stores during prolonged cold storage is one of the most critical events of cold ischemia-reperfusion (CI/R) injury. The aim of this study was to evaluate the effect of hyperbaric oxygen (HBO) treatment on CI/R injury. METHODS: Livers were harvested from male Wistar rats and stored for 24 h at 4 degrees C in University of Wisconsin solution (Group 1). Others were additionally treated with HBO during the preservation period (Group 2). At the end of the 24 h cold preservation, the concentrations of hepatic enzymes and lipid peroxidation (LPO) in the effluent and the hepatic adenosine triphosphate (ATP) levels were measured. After preservation, the livers were reperfused for 90 min with an oxygenated Krebs-Henseleit bicarbonate buffer. Perfusate samples were obtained serially, and portal flow rates were also recorded. RESULTS: In group 2, aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and LPO into the effluent at the end of preservation were decreased and the depletion of ATP was prevented (P<0.05). After reperfusion, the portal flow was significantly improved in group 2 (P<0.05). The time-dependent increase of alanine aminotransferase levels (ALT) observed in group 1 was suppressed significantly in group 2, and total bile production during 90 min of reperfusion was significantly greater in group 2 (P<0.05). The structure of the livers in group 2 was significantly well maintained, and the liver weight change ratio was significantly greater in group 1 (P<0.05). CONCLUSIONS: HBO treatment during cold storage seems to prevent hepatic ischemic injury and have protective effects against CI/R injury by attenuating the depletion of energy stores.

Adenosine Triphosphate↗

Is acetylcholinesterase activity in neorectum after laparoscopic endorectal pull-through method for Hirschsprung's disease a primary or a secondary condition?

Between 1996 and 2002, 22 cases of Hirschsprung's disease were treated laparoscopically by endorectal pull-through operation. The proximal margin of the resected bowel materials from these 22 patients were examined histologically by frozen sections at surgery and also after surgery using H&E staining, and complete resection of the aganglionic segment was confirmed. Eleven patients, in whom an informed consent was obtained at randomly, underwent suction biopsy from the pulled-though neorectum after surgery. Of these 11 patients, 2 revealed many AchE-positive nerve fibers in the lamina propria, the muscularis mucosa and around the ganglion cells in the submucosal plexuses. These structural changes were similar to intestinal neuronal dysplasia that was characterized by hyperganglionosis and other neuronal abnormalities. The remaining 9 revealed no AchE activity. Unexpectedly, the two patients showing AchE activity in their neorectum continued to have persistent constipation and were treated with laxatives or glycerin enema. It was suggested that their persistent constipation was caused by intestinal neuronal dysplasia showing an abnormal increase of AchE activity in spite of presence of ganglion cells of the neorectum after surgery, but it was uncertain that they were primary condition as a HaIND or secondary reactions after surgery.

Acetylcholinesterase↗

Poorly differentiated neuroendocrine cell carcinoma of the rectum: report of a case and literal review.

A 56-year-old man was admitted to our hospital because of anal bleeding. Colonoscopy and barium enema revealed type 4 tumor in the rectum. Biopsy revealed poorly differentiated adenocarcinoma. Low anterior resection with total mesorectal excision and lymph node dissection was performed. In immunohistochemical staining, chromogranin A and synaptophysin were positive at major lesion, and CEA were focal positive. The resected tumor was diagnosed pathologically as neuroendocrine cell carcinoma. The Ki-67 labeling index (LI) was 87.8%, so proliferative activity and potential malignancy was very high. Multiple metastatic tumors appeared in pelvis and lung eight months after operation. Treatment for neuroendocrine cell carcinoma of the rectum was controversial. Surgical resection and adjuvant chemotherapy might be one of the methods for gastrointestinal neruroendocrine cell carcinoma.

Biopsy↗

Rapid-growing solitary necrotic nodule of the liver.

The solitary necrotic nodule of the liver is an uncommon nonmalignant lesion with an uncertain etiology. The lesion was defined as a nodule with a completely necrotic core and fibrous capsule etc. and without a consistency of viable cells. The characteristic features of this benign lesion on the imaging modalities are similar to the metastatic tumor. In this paper we discuss the case of a rapid-growing solitary necrotic nodule of the liver occurring in a patient with chronic renal failure on hemodialysis. The lesion located on the left median lobe of the liver had rapidly enlarged in diameter in the last seven months. Despite some examinations by imaging modalities to confirm the preoperative diagnosis, we were unable to visually confirm. Several histological examinations using a needle biopsy specimen were performed, but the diagnosis was all necrotic tissue. However, we recommended an extended left hepatic lobectomy for this rapid-growing lesion since cholangiocarcinoma with necrosis could be hardly differentiated. Permanent histology revealed that the lesion was solitary necrotic nodule. We consider that permanent histology of the entire lesion is possibly the only accurate method of diagnosis. Since the solitary necrotic nodule does not indicate malignancy, hepatic resection should be performed.

Bile Duct Neoplasms↗

Prevention of lethal hepatic injury in Long-Evans Cinnamon (LEC) rats by D-galactosamine hydrochloride.

Repeated injections of D-galactosamine hydrochloride (GalN) increase the survival rate of Long-Evans Cinnamon (LEC) rats, an animal model of Wilson's disease. The aim of the present study was to investigate the mechanism of GalN for prevention of spontaneous lethal hepatic injury in LEC rats. Male LEC rats were given a single subcutaneous injection of 300 mg/kg of GalN or vehicle (0.9% NaCl) at 14 weeks, and killed at 28 weeks of age. Next, 6-week-old male LEC rats were given weekly subcutaneous injections of 300 mg/kg of GalN or vehicle for 3 or 12 weeks, and their hepatic 8-hydroxydeoxy-2'-guanosine (8-OHdG), glutathione peroxidase (GPX), and catalase activities were measured. None of GalN-treated rats died of hepatic injury (0/12), whereas the mortality rate of control rats given 0.9% NaCl was 17% (2/12). GalN administration for 12 weeks decreased the hepatic 8-OHdG, and GalN administration for either 3 or 12 weeks increased the glutathione peroxidase activity. GalN administration increased the serum level of alanine aminotransferase, and accelerated megalocytic degeneration of the hepatocytes. GalN treatment is effective in preventing lethal hepatitis in LEC rats and decrease of oxidative DNA damage by GalN plays an important role in increase of the survival rate.

Animals↗

In situ dye injection bile leakage test of the graft in living donor liver transplantation.

BACKGROUND: Bile leakage after living donor liver transplantation (LDLT) remains a serious problem, resulting in lower survival rates. The aim of this study is to clarify the benefits of in situ leakage testing of the cut surface of grafts in LDLT. METHODS: A total of 135 LDLTs were analyzed. The patients were divided into the following two groups according to the in situ dye injection leakage test of the cut surface: test group (n=40) and control group (n=40). The incidence of bile leakage and the risk factors were identified by analyzing the recipients, donors, and transplantation variables. RESULTS: Bile leakage occurred in 12.5% (10/80) of LDLTs. In the control group, there were nine cases of bile leakage (22.5%). On the other hand, there was only one case (2.5%) of bile leakage in the test group (P<0.05). The bile leakage case in the test group was resolved preservationally. However, 2 of the 9 (22.2%) bile leakage cases in the control group required surgery. CONCLUSION: Although there is biliary complication, especially bile leakage from the cut surface, as an inevitable consequence of LDLT, this study suggests that there is advantage in conducting bile leakage testing to minimize the incidence of bile leakage from the cut surface, which is associated with a high risk of graft failure.

Adult↗

Significance of the relationship between irregular regeneration and two hepatocarcinogenic pathways: "de novo" and so-called "dysplastic nodule-hepatocellular carcinoma" sequence.

BACKGROUND AND OBJECTIVES: Irregular regeneration of hepatocytes has been reported as an important factor in the hepatocarcinogenesis, so we studied the relationship between irregular regeneration and two hepatocarcinogenic pathways, "de novo" and "dysplastic nodule-hepatocellular carcinoma sequence." METHODS: Liver tissue was obtained from surgically resected 112 specimens, early well differentiated hepatocellular carcinomas and non-cancerous tissue. Hepatocellular carcinomas were divided into two groups; carcinoma with dysplastic area (type A) and without dysplastic area (type B) and were compared with irregular regeneration of hepatocytes in the non-cancerous tissue. RESULTS: Eighty-eight of 112 cases were judged to have irregular regeneration, such as anisocytosis, pleomorphism, bulging and map-like distribution. The degree of irregular regeneration was not correlated to the type of early well differentiated hepatocellular carcinomas. However, the existence of pleomorphism, map-like distribution and bulging are significantly correlated with type A. CONCLUSION: Type A might be more frequently occurring in a carcinogenic liver showing some kinds of irregular regeneration.

Carcinoma, Hepatocellular↗

Impact of graft hepatic vein inferior vena cava reconstruction with graft venoplasty and inferior vena cava cavoplasty in living donor adult liver transplantation using a left lobe graft.

BACKGROUND: Hepatic venous reconstruction is critical in living donor adult liver transplantation (LDALT) because outflow obstruction in small for size graft may lead to graft dysfunction or loss. We describe the usefulness of venoplasties of the graft hepatic vein (HV) and graft HV-recipient inferior vena cava (IVC) reconstruction in LDALT using a left lobe graft. METHODS: Sixty patients who underwent LDALT were studied. We divided the patients into following two groups: venoplasty group (n=30) and control group (n=30). For the patients with venoplasty group, venoplasty of the graft and recipient IVC cavoplasty was made to widen the orifice. Comparison examination of a background factors and postoperative bilirubin and the ascites was carried out. RESULTS: The mean graft volume standard liver volume ratio (GV/SLV) did not have the difference at 41.7% of venoplasty group, and 42.1% of control group (p=NS). The diameter of the hepatic vein in control and venoplasty group before and after venoplasty is 26.9+/-5.5, 28.2+/-2.9, and 34.1+/-3.9 mm, respectively. The diameter of the hepatic vein after venoplasty is larger than that of before venoplasty and of control (P<0.05). Mean total bilirubin level on postoperative day (POD) 7 is 13.8+/-9.3 mg/dl in control group and 7.0+/-3.3 mg/dl in venoplasty group (P<0.05). Mean amount of ascites on POD 7 and 14 are 1576+/-1113 and 1397+/-1661 cc in control group, and 736+/-416 and 550+/-385 cc in venoplasty group, respectively (P<0.05). Two-year survival rate is 75.2 % in control group and 86.6 % in venoplasty group (P<0.05). CONCLUSIONS: We conclude that in LDALT using left lobe graft, HV-IVC reconstruction with graft venoplasty and IVC cavoplasty is useful not only to prevent outflow block but also to improve graft function.

Aged↗

Short-term intensive treatment for donors with hepatic steatosis in living-donor liver transplantation.

BACKGROUND: The use of steatotic livers is associated with increased primary nonfunction in liver transplantation. To reduce the risk of liver injury, we applied a short-term combination therapy of diet, exercise and drugs for 11 living-donor liver transplantation (LDLT) candidates with steatosis. METHODS: Subjects were treated with a protein-rich (1000 kcal/day) diet, exercise (600 kcal/day), and bezafibrate (400 mg/day) for 2-8 weeks. RESULTS: The treatment significantly improved macrovesicular steatosis (30+/-4% vs. 12+/-2% [mean +/- SEM], P = 0.0028). Body weight and BMI were significantly reduced (73.7 +/- 3.2 kg vs. 66.9 +/- 2.9 kg, P = 0.0033, 26.4 +/- 0.7 kg/m vs. 24.1 +/- 0.8 kg/m, P = 0.0033). The treatment completely normalized liver function tests and lipid metabolism. Seven treated liver grafts (left lobe) were transplanted to the recipients. We compared transplanted graft function and resected liver function of donors using parameters such as peak total bilirubin, prothrombin time at postoperative day 3, and peak alanine aminotransferase between treated liver (n = 7) and donor liver without hepatic steotosis (n = 37). The transplanted grafts showed good liver functions, and there was no difference between them with respect to functional parameters. The treated donors also showed good liver functions, and no significant differences in functional parameters. CONCLUSIONS: The results of this study indicate that our short-term treatment effectively reduced steatosis and contributed to safer LDLT. Our findings also suggest that even severely steatotic livers can be used for LDLT grafting subsequent to our short-term treatment regimen.

Adult↗