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Aim: Direct-acting antivirals for hepatitis C virus have reduced the decompensation risk. Immunosuppressants for transplantation raise the risk of occurrence of de novo malignancies. We assessed the probabilities of and risk factors for de novo hepatocellular carcinoma (HCC) development post-living donor liver transplantation (LDLT)., Methods: We retrospectively evaluated the data of developed HCC in a graft including metastatic HCC post-LDLT from 2779 adult cases collected from nine major liver transplantation centers in Japan., Results: Of 2779 LDLT adult recipients, 34 (1.2%) developed HCCs in their grafts. Of 34, five HCCs appeared to be de novo because of a longer period to tumor detection (9.7 [6.4-15.4] years) and no HCC within the native liver of the two recipients. The donor origin of three of five de novo HCCs was confirmed using microsatellite analysis in resected tissue. Primary disease of all five was hepatitis C virus-related cirrhosis, of which two were treated with direct-acting antivirals. Four of five developed HCC de novo in the hepatitis B core antibody-positive grafts. De novo HCCs had favorable prognosis; four of five were cured with complete remission. However, recurrent HCC (n = 29) in the graft had a poorer outcome, especially in patients with neutrophil to lymphocyte ratio scores above 4 (median survival time, 262 [19-463] days)., Conclusion: Analysis of the database from major liver transplantation institutes in Japan revealed that de novo HCCs determined by microsatellite analysis were rarely detected, but the majority were successfully treated. LDLT recipients with higher risks of de novo HCC, including those with hepatitis B core antibody-positive grafts, should be carefully followed by surveillance of the liver graft., (© 2020 The Japan Society of Hepatology.)

Aim: Cell-based transplantation is an alternate method of liver transplantation to delay the onset of end-stage liver diseases. For successful treatment, cells need to be expended in vitro expeditiously. However, autogenetic hepatocytes as the ideal cell source for therapy remain in quiescence so proliferation is rare. Photobiomodulation therapy has been used to stimulate some kinds of cell proliferation, but is unknown whether red light-emitting diode (LED) irradiation can promote primary hepatocyte proliferation. The aim of this study was to evaluate the effect of red LED irradiation on hepatocytes in vitro., Methods: Mouse primary hepatocytes were isolated and received red LED treatment. The cell viability, reactive oxygen species (ROS) levels, phosphorylated extracellular signal-regulated kinase1/2 (pERK1/2) and some cell cycle-related proteins were observed. Additionally, ROS inhibition and pERK1/2 inhibition were carried out to determine the effect of ROS and ERK1/2 in red LED irradiation., Results: The red LED irradiation increased hepatocyte proliferation, elevated intracellular ROS levels, and stimulated ERK1/2 activation and cell cycle-related gene expression. The mitosis promoting effect of red LED irradiation could be disturbed by ROS or pERK inhibition. The red LED irradiation promoted hepatocyte proliferation through the ROS/pERK1/2 pathway., Conclusions: Red LED irradiation could accelerate hepatocyte proliferation through the ROS/pERK1/2 pathway. Red LED irradiation might be a potential method to increase hepatocyte cell numbers in vitro and support cell-based transplantation in clinical work., (© 2018 The Japan Society of Hepatology.)

Aim: Splenectomy is a well-known procedure to improve thrombocytopenia and liver function in patients with liver cirrhosis (LC). However, the effect of splenectomy on liver regeneration remains unclear. The aim of this study is to investigate the effect of splenectomy on liver regeneration., Methods: Twenty patients with LC who underwent splenectomy were included in this study. Liver and splenic volumes were measured by a 3-D simulation imaging system. Liver volume (LV) and clinicopathological data were compared before and 6 months after splenectomy. Thereafter, patients were divided into two groups: the elevated LV group and the reduced LV group. Patient characteristics were compared between the two groups., Results: Postoperative LV was increased in 14 patients compared with the preoperative state. Thrombocytopenia, leukopenia, total bilirubin and prothrombin time were improved after splenectomy. In the elevated LV group, four patients exhibited improved Child-Pugh grades after splenectomy, whereas no patients demonstrated improvement in the reduced LV group. The elevated LV group exhibited high albumin level, good indocyanine green retention rate at 15 min and large splenic volume compared with the same measurements in the decreased group. Patients with larger spleen volumes and higher albumin values before splenectomy showed increased rates of LV after splenectomy., Conclusion: Splenectomy for patients with LC improved pancytopenia and liver function. Especially, in patients with large spleen and high albumin levels, considerable increases in LV and improved liver function were observed., (© 2015 The Japan Society of Hepatology.)

Preoperative estimation of liver functional reserve is important in liver surgery to prevent postoperative liver failure. Although the hepatic functional reserve of patients with chronic liver disease is generally evaluated by measuring indocyanine green dye retention at 15 min, no standard method of estimating regional liver function has been established to date. Several recently introduced imaging modalities, such as hepatobiliary scintigraphy and magnetic resonance imaging with gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid, may be used to evaluate liver function. Here, we review recent advances in estimating hepatic functional reserve, mainly by radiological modalities, in patients with chronic liver damage., (© 2014 The Japan Society of Hepatology.)

Aim: FBXW7 acts as a tumor suppressor gene by targeting several oncogenic regulators of proliferation, growth and apoptosis for proteasomal degradation. However, the significance of this protein is not yet well understood in intrahepatic cholangiocarcinoma (IHCC). In this study, we aimed to investigate the correlation between FBXW7 expression and clinicopathological variables in IHCC patients., Methods: Thirty-one patients with IHCC who underwent hepatic resection were enrolled. FBXW7 expression in tumor tissue was determined by immunohistochemistry and patients were divided into two groups, the FBXW7 high expression group (n = 11) and the FBXW7 low expression group (n = 20). We then compared clinicopathological variables including prognosis between the high and low expression groups in tumor tissue., Results: FBXW7 expression was significantly correlated with staging (P = 0.006), and tended to correlate with lymph node metastasis. The FBXW7 low expression group had significantly poorer prognosis compared with the FBXW7 high expression group (P = 0.020); 3-year survival rates were 29.4% and 72.7%, respectively. Furthermore, the disease-free survival rate in the FBXW7 low expression group was significantly worse than in the FBXW7 high expression group (P = 0.022). On multivariate analysis, intrahepatic metastasis (P = 0.006) was a significant independent prognostic factor for disease-free survival, and FBXW7 low expression tended to be an independent prognostic factor for both overall (P = 0.067) and disease-free survival (P = 0.083)., Conclusion: Our results confirmed that low expression of FBXW7 in IHCC correlates with tumor progression and poor prognosis in IHCC., (© 2014 The Japan Society of Hepatology.)

Aim: It is unclear whether the spleen affects the progression of liver cirrhosis (LC) through "liver-spleen cross-talk". Transforming growth factor-β1 (TGF-β1) is reported to be the most potent cytokine of liver fibrosis, and interleukin-6 (IL-6) is an important factor of liver regeneration. In this study, we investigated the expression of cytokines in the spleens of LC patients in order to attempt to prove the existence of liver-spleen cross-talk., Methods: The study enrolled 22 patients who underwent splenectomy at our institute between 2004 and 2010. TGF-β1 expression in the resected spleen was measured using immunohistochemical staining. Two-color immunofluorescent staining for CD68 and TGF-β1 in the spleen was performed to detect sources of TGF-β1. IL-6 expression in the spleen was measured by reverse transcription polymerase chain reaction., Results: TGF-β1 expression was significantly higher in the spleens of LC patients than in those of patients with normal livers (P < 0.05). Coexpression of CD68 and TGF-β1 was confirmed. The expression of IL-6 in the spleens of LC patients was significantly lower than that in patients with normal livers (P < 0.05)., Conclusion: TGF-β1 produced by macrophages and cytokines such as IL-6 could affect the progression of liver fibrosis and regeneration in patients with LC via liver-spleen cross-talk., (© 2013 The Japan Society of Hepatology.)

Aim: The nutritional state of living donor liver transplantation (LDLT) recipients is one of the most important factors affecting postoperative outcome. Although the assessment of health-related quality of life (HRQOL) is of increasing importance, few studies have examined this in conjunction with LDLT recipient nutritional state., Methods: Ten LDLT recipients with end-stage liver disease were recruited for this study. Measurements of energy expenditure, anthropometrics and laboratory data were performed before and 1, 6 and 12-24 months after LDLT. HRQOL was measured by using the 36-item Short-Form (SF-36) before and 1, 3, 6 and 12-24 months after LDLT., Results: The preoperative value of non-protein respiratory quotient (npRQ) was 0.796 ± 0.026 and it increased significantly after the operation. Serum non-esterified fatty acid (NEFA) levels were high in the preoperative state, but had significantly decreased 1 month after the operation. A negative correlation between npRQ and NEFA was observed throughout the study period. Cholinesterase and albumin levels improved to normal levels within 6 and 12-24 months, respectively. The recovery of the physical component summary of the SF-36 was observed after the improvement of all domains of laboratory data and energy metabolism based on the nutritional state., Conclusion: This study demonstrated that the recovery of metabolic function, laboratory data and HRQOL in LDLT recipients are variable, and it took more than 6 months to normalize the liver protein synthetic capacity and physical HRQOL score periods. Therefore, long-term nutritional support is required in LDLT recipients., (© 2013 The Japan Society of Hepatology.)

Aim: It is reasonable to investigate non-tumor liver tissues to predict a risk for development of hepatocellular carcinoma (HCC). A molecular analysis of chronically damaged liver tissues may identify specific miRNA expression profiles associated with a risk for multicentric (MC) HCC., Methods: Twenty HCC patients, who underwent a curative hepatectomy were classified into two groups: a non-MC group (no MC recurrence in more than 3 years, n = 10) and an MC group (MC recurrence within 3 years after hepatectomy, n = 10). An miRNA microarray (955 probes) was used to compare the miRNA expression patterns of the non-cancerous liver tissues between the two groups. This study identified the differentially expressed miRNA related to MC recurrence in the liver remnant., Results: No differences were observed between the two groups in the liver function tests and pathological variables including both tumor factors and non-tumor liver tissues. The investigation selected 20 differentially expressed miRNA related to MC recurrence. Eighteen miRNA were downregulated, while two miRNA were upregulated in the MC group. A hierarchical clustering analysis identified a cluster that may be associated with risk of the MC recurrence of HCC. The MC recurrence-related miRNA included let-7d*, miR-328 and miR18a*, which potentially regulate K-ras gene expression. A significant inverse correlation between the miR-18a* expression and the K-ras mRNA expression was confirmed by quantitative reverse transcription polymerase chain reaction., Conclusion: Specific miRNA expression signatures in non-cancerous liver tissue may help to predict the risk for de novo development of HCC., (© 2013 The Japan Society of Hepatology.)

Aim: This study examined the efficacy of enteral nutrition containing hydrolyzed whey peptide (HWP) on warm ischemia/reperfusion (I/R) injury in the rat liver., Methods: Male Wistar rats were subjected to 30 min of warm hepatic ischemia followed by immediate p.o. intake of enteral nutrition with WHP (HWP group) or 20% glucose solution (control group) (0.025 mL/g). The animals were killed at 6 or 12 h after reperfusion. The serum aspartate aminotransferase (AST) and alanine aminotransferase alt (ALT) levels were measured. The necrotic areas were assessed histologically. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and caspase-3 activation were assessed to evaluate apoptosis. The expressions of hepatic tumor necrosis factor (TNF)-α, interleukin (IL)-6 and nuclear factor (NF)-κB in the liver tissue were assessed by real time reverse transcription polymerase chain reaction., Results: Significant reductions in the serum AST and ALT levels were seen in the HWP group compared with the control group at both 6 and 12 h after reperfusion. The necrotic areas and numbers of TUNEL positive cells were significantly decreased in the HWP group at 6 and 12 h after reperfusion. The caspase-3/7 activities were significantly decreased in HWP group at 6 and 12 h after reperfusion. The mRNA expressions of TNF-α and IL-6 were significantly reduced in the HWP group at 12 h after reperfusion. NF-κB mRNA expression was significantly increased in the HWP group at 6 and 12 h after reperfusion., Conclusion: Enteral nutrition containing HWP ameliorated the hepatic warm I/R injury possibly through the suppression of pro-inflammatory cytokine expressions and the induction of NF-κB in the rat liver., (© 2013 The Japan Society of Hepatology.)

A 40-year-old woman who had undergone a curative low anterior resection for advanced rectal cancer was admitted to our hospital. She had been administrated oxaliplatin-based chemotherapy as postoperative adjuvant chemotherapy. The contrast-enhanced computed tomography revealed three hypovascular tumors, 3.0, 1.5 and 1.0 cm in diameter, located in the right hepatic lobe. The hepatocyte phase of the gadoxetic acid-enhanced magnetic resonance imaging demonstrated these lesions as hypointense tumors relative to the surrounding hepatic parenchyma. All these findings of the preoperative imaging modalities were compatible to metastatic liver tumors from the rectal cancer, and right hepatic lobectomy was successfully performed. Histopathologically, the tumors revealed sinusoidal dilation and severe congestion outlined by atrophic hepatocyte trabeculae, which was known as peliosis hepatis. The perisinusoidal space of Disse was extensively dilated and contained many erythrocytes. Taking these findings into account, the hepatic tumors were considered to be the space-occupying lesions resulting from the sinusoidal obstruction syndrome. We herein report the first case of focal sinusoidal obstruction syndrome mimicking metastatic liver tumors., (© 2013 The Japan Society of Hepatology.)

Aim:   Lens culinaris agglutinin A-reactive fraction of α-fetoprotein (AFP-L3) status has been reported to be an independent prognostic factor in patients with hepatocellular carcinoma (HCC). In this study, we evaluated the clinical usefulness of measuring preoperative AFP-L3 to predict the recurrence and prognosis of HCC after curative hepatectomy., Methods:   One hundred and forty-two HCC patients who underwent curative hepatectomy were examined for the correlation between preoperative tumor marker, including AFP, des-γ-carboxy prothrombin (DCP) and AFP-L3, and clinicopathological variables. The prognostic factors of disease-free survival rates and overall survival rates were also determined using clinicopathological variables including these three tumor markers., Results:   There were similar tendencies in the relationship between these three markers and malignant behaviors including lower grade tumor differentiation or vascular invasion. In multivariate analysis, increased AFP-L3 value (P = 0.019) was found to be an independent prognostic factor of disease-free survival after curative hepatectomy. In addition, elevated DCP (P = 0.013) and AFP-L3 values (P = 0.012) were found to be independent prognostic factors. Furthermore, the preoperative AFP-L3 value in the patients with early recurrence (within 1 year after hepatectomy) was significantly higher than that in those without early recurrence (26.9 ± 19.5 % vs 14.2 ± 19.8 %, P = 0.047)., Conclusion:   Preoperative AFP-L3 value was strongly correlated to disease-free and overall survival rate and the timing of recurrence, so it appears that it would be useful to predict the recurrence and prognosis of HCC after curative hepatectomy., (© 2012 The Japan Society of Hepatology.)

Aim:   Current medical transplantation methods focus on solutions for major problems such as the shortage of donors. To overcome these issues, expanding organ preservation time has become a major concern. A new refrigerating chamber has been recently developed, which can cool the inside of a material to the required temperature by frequently sensing the temperature of both inside and surface of the materials. The purpose of this study is to evaluate the usefulness of a new refrigerating system in hepatic preservation., Methods:   The liver grafts were harvested from rats and divided into two groups. Group A consisted of grafts preserved in chilled University of Wisconsin solution (UW) solution (on ice) for 24, 72 and 168 h. Group B consisted of grafts preserved in the UW solution in a new refrigerator at 4°C., Results:   In group B, aspartate aminotransferase released into effluent after cold storage for 72 h showed a marked decrease compared to group A (P < 0.05). The levels of ammonia and lactate decreased significantly in group B (P < 0.05). In group B, the levels of adenosine triphosphate were significantly preserved after cold storage for 24 h and 72 h compared to group A (P < 0.05). Immunohistochemistry showed positive cells for heme oxygenase-1 were significantly increased in group B after cold storage., Conclusion:   This new refrigerator can improve preservation injury of hepatic grafts and may provide an innovative technique for liver transplantation., (© 2012 The Japan Society of Hepatology.)

We present a 43-year-old man with huge focal nodular hyperplasia (FNH) that was difficult to distinguish from well-differentiated hepatocellular carcinoma (HCC). He previously had abnormal portal vein circulation due to hypoplasia of the intrahepatic portal vein, which was treated with a superior mesenteric vein-inferior vena cava shunt. Laboratory findings included predominantly indirect hyperbilirubinemia with concomitant elevation in aspartate aminotransferase (AST), alanine aminotransferase (ALT), and ammonia. Serum α-fetoprotein and des-γ-carboxy prothrombin were slightly elevated. Multidetector-row computed tomography detected the primary tumor in the left liver lobe, which partially showed a central stellate scar. Gd ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging showed some low-intensity areas in the tumor in the hepatocyte phase. 99mTc-galactosyl human serum albumin scintigraphy showed normal intake of agent in the tumor. We could not rule out well-differentiated HCC. Extended left hepatectomy was performed. Final histopathological findings showed that most of the tumor was FNH against a background of portal vein hypoplasia with moderate atypia and hemorrhage. And immunohistochemical analysis revealed high expression of organic anion transporter (OATP) 1B3 and low expression of multidrug resistance-associated protein (MRP) 2 in a part of the tumor. The patient has remained alive with no hepatic lesion for 1 year after surgery. We describe a case of huge FNH that was difficult to distinguish from well-differentiated HCC even by current fully preoperative imaging technology and demonstrate the effectiveness of curative surgical resection., (© 2012 The Japan Society of Hepatology.)

Aim:   The aim of this study was to investigate the characteristics of super-elderly hepatocellular carcinoma (HCC) patients aged 80 years or more who underwent hepatectomy and to clarify whether elderly patients with HCC benefit from hepatectomy., Methods:   Between March 1992 and December 2008, 278 patients who underwent curative hepatectomy for HCC were investigated. Super-elderly patients were defined as those aged 80 years or more. Clinicopathological data and outcomes after hepatectomy were compared between super-elderly and non-super-elderly groups., Results:   Preoperative parameters, such as biochemical examinations, and liver function tests in the non-super-elderly group were comparable with those of the super-elderly group (n = 11). Exceptionally, albumin level in the super-elderly group was lower than that in the non-super-elderly group (P = 0.03). Surgical data and the prevalence of postoperative complications did not differ significantly between the two groups. No mortality was observed in the super-elderly and non-super-elderly group., Conclusions:   Hepatectomy for HCC was a feasible option even in super elderly patients aged 80 years or older with accurate selection., (© 2012 The Japan Society of Hepatology.)

Aims:   Dihydropyrimidine dehydrogenase (DPD) and thymidylate synthase (TS) are key enzymes in the metabolism of 5-fluorouracil and have been implicated as possible prognostic markers for cancer patients. However, the clinical roles of DPD and TS in intrahepatic cholangiocarcinoma (IHCC) have not been investigated. The aim of this study was to clarify the clinicopathological role of DPD and TS expressions in IHCC., Methods:   Twenty-nine patients who had undergone hepatic resection for IHCC were enrolled in this study. Expressions of DPD and TS in the resected IHCC specimens were examined using anti-DPD or anti-TS antibody. The patients were divided into positive and negative groups according to DPD/TS expressions: DPD-positive group (n = 18) and DPD-negative group (n = 11)/TS-positive group (n = 14) and TS-negative group (n = 15). Clinicopathological factors were compared between the two groups., Results:   The overall survival rate was significantly lower in the DPD-negative group than in the DPD-positive group (1-year 36.4% vs. 77.4%, 3-year 18.2% vs. 43.0%; P < 0.05). The disease-free survival rate in the DPD-negative group tended to be lower than that in the DPD-positive group. The overall survival rate or disease-free survival rate did not appear to be associated with the TS-expression status. The Ki-67 labeling index in the DPD-negative group was significantly higher than that in the DPD-positive group (16.9 ± 3.2% vs.13.2 ± 3.3%; P < 0.05)., Conclusions:   The negative DPD expression was significantly associated with the enhanced tumor cell proliferation and poorer prognosis in patients with IHCC. DPD expression is a potential prognostic indicator for IHCC., (© 2010 The Japan Society of Hepatology.)

Aim:   With the recent advances in medical or surgical treatments in chronic hepatic disorders, the indications for splenectomy in hepatic disorders have greatly expanded. We performed splenectomy for cirrhotic patients and investigated the effects of splenectomy on hepatic functional reserve and nutrition metabolism., Methods:   Eighteen patients (Child-Pugh B/C: 12/6; Child-Pugh A: excluded) who underwent splenectomy at our institute between 2005 and 2008 were enrolled. Twelve patients (67%) had hepatocellular carcinoma (HCC), eight of whom met the Milan criteria., Results:   Overall survival rate was 83.3% at 1 year and 62.7% at 2 years. The survival rate of six patients with liver cirrhosis classified a Child-Pugh C was 80.0% at 1 year and 60.0% at 2 years. Three patients underwent hepatic resection and nine patients received ablation therapy against hepatocelluar carcinoma. Portal pressure decreased after splenectomy in most patients (mean decrease, 4.7 mmHg). Four weeks after the operation, the markers of hepatic functional reserve, indocyanine green retention rate at 15 min (ICGR15) and Technetium-99m-galactosyl human serum albumin value ((99m)Tc-GSA), improved from 38.5% to 35.1% and from 0.773 to 0.788 (LHL15), respectively. The non-protein respiratory quotient (npRQ) did not change in short period after the operation. Other outcomes, including liver function test in cirrhotic patients with long-term (1 year) follow-up after splenectomy (n = 7), did not improve significantly. Post-operative complications included portal thrombus (n = 2), ascites (n = 2) were observed in six patients (33%)., Conclusion:   Splenectomy improved hepatic functional reserve and nutritional metabolism in some cases. However, the long-term outcomes should still be evaluated.

Aim: In patients with liver cirrhosis, abnormal energy metabolism induces low health-related quality of life (HRQOL) scores. However, late-evening snack (LES) prevents morning starvation in cirrhotic patients. Our aim is to assess the effect of long-term LES on HRQOL in cirrhotic patients, using the 36-item Short Form (SF-36) health survey., Methods: Thirty-nine cirrhotic patients classified as Child-Pugh grade A were recruited. The patients were randomly divided into two groups: 24 were assigned to the non-LES group and 15 to the LES group. SF-36 scores, anthropometric data and serum biochemical parameters were examined in the non-LES and LES groups at 0, 6 and 12 months., Results: Neither anthropometric data nor laboratory data showed significant differences between the non-LES and the LES groups at 0, 6 and 12 months. The role-emotional (RE) HRQOL scores at 6 months and mental health (MH) scores at 6 and 12 months were significantly reduced from the baseline level in the non-LES group. In contrast, these scores remained unchanged in the LES group. General health perception (GH) scores at 12 months, RE at 6 months and MH at 6 and 12 months in the LES group were significantly higher than those of the non-LES group., Conclusion: Long-term LES administration may be helpful in maintaining higher HRQOL in patients with cirrhosis.

Aim: Possible spleno-hepatic relationships during hepatectomy remain unclear. The purpose of this study was to investigate the impact of splenectomy during massive hepatectomy in rats., Methods: Rats were divided into the following two groups: 90% hepatectomy (Hx group), hepatectomy with splenectomy (Hx+Sp group). The following parameters were evaluated; survival rate, biochemical parameters, quantitative RT-PCR for hemeoxygenase-1 (HO-1) and tumor necrosing factor alpha (TNFalpha), immunohistochemical staining for HO-1, proliferating cell nuclear antigen labeling index and liver weights., Results: The survival rate after massive hepatectomy significantly improved in Hx+Sp group as well as serum biochemical parameters, compared with Hx group (P < 0.05). HO-1 positive hepatocytes and its mRNA expression significantly increased and TNFalpha mRNA expression significantly decreased in Hx+Sp group compared with Hx group (P < 0.05). Moreover, liver regeneration was significantly accelerated at 48 and 72 h after hepatectomy in Hx+Sp group., Conclusions: Splenectomy had beneficial effects on massive hepatectomy by ameliorating liver injuries and promoting preferable liver regeneration.

Aim: The significance of dihydropyrimidine dehydrogenase (DPD) and thymidylate synthase (TS) gene expressions for the post-surgical prognosis of hepatocellular carcinoma (HCC) has not yet been determined. In the present study, we clarified the significance of DPD and TS gene expressions for the prognosis of HCC., Methods: Seventy-four patients, who underwent curative hepatic resection for primary HCC, were evaluated. The DPD and TS mRNA levels of the resected HCC specimens were evaluated using a microdissection technique and quantative real-time RT-PCR. The patients were categorized into high and low groups for each mRNA based on the median value. Various clinicopathological factors, including prognosis, and proliferation index using Ki-67 staining were evaluated in association with the DPD and TS mRNA expression levels., Results: The low DPD mRNA expression was related to younger age, advanced clinical stage, undifferentiated histology, and microscopic intrahepatic metastasis. The overall and recurrence-free survival were significantly lower in the low DPD group than in the high DPD group (P < 0.05). Furthermore, the proliferation index in the low DPD group was significantly higher than that in the high DPD group (P < 0.01). On the other hand, the high TS group showed a tendency of better prognosis than the low TS group, although it was not statistically significant., Conclusions: The low DPD mRNA expression is a significant poor prognostic factor. after curative resection of HCC.

For years splenectomy in hepatic disorders has been indicated only for the treatment of gastro-esophageal varices. However, with recent advances in medical and surgical treatments for chronic hepatic disorders, the use of splenectomy has been greatly expanded, such that splenectomy is used for reversing hypersplenism, for applying interferon treatment for hepatitis C, for treating hyperdynamic portal circulation associated with intractable ascites, and for controlling portal pressure during small grafts in living donor liver transplantation. Such experiences have shown the importance of portal hemodynamics, even in cirrhotic livers. Recent advances in surgical techniques have enabled surgeons to perform splenectomy more safely and less invasively, but the procedure still has considerable clinical outcomes. Splenectomy in hepatic disorders may become a more common procedure with expanded indications. However, it should also be noted that the long-term effects of splenectomy, in terms of improved hematological or hepatic function, is still not guaranteed. Moreover, the impact of splenectomy on immunologic status remains unclear and needs to be elucidated in both experimental and clinical settings.

Aim: Inchin-ko-to (ICKT), Kampo medicine, is known to inhibit hepatocyte apoptosis as well as promote the secretion and excretion of bile. The aim of this study is to clarify the effects of ICKT on liver function and hepatic regeneration after massive hepatectomy in rats., Methods: Male Wistar rats received 2 g/kg ICKT from 3 days preoperatively and underwent 90% hepatectomy. Liver sections were stained using immunohistochemistry (hemeoxygenase-1 [HO-1], alpha-smooth muscle actin [SMA], and proliferating cell nuclear antigen [PCNA])., Results: The survival period was significantly prolonged, and the remnant liver/body weight ratio was significantly increased postoperatively in the ICKT group. The values of transaminase, total bile acid, and total bilirubin were significantly improved in the ICKT group. In the ICKT group, PCNA and HO-1 were strongly expressed early postoperatively, but the expression of alpha-SMA was weak., Conclusion: The preoperative administration of ICKT has been suggested to provide beneficial effects in promoting hepatic regeneration and preventing postoperative hepatic failure. The reduced activation of stellate cells may be involved in their mechanisms.

Although a mucoepidermoid carcinoma is sometimes seen as a neoplasm originating from the salivary glands, its origination from the liver is rare. A review of the medical literature in the English language disclosed only 16 cases originating from the hepatic system. The case explored here is that of an 81-year-old female, without any significant medical history, who was referred to our hospital for elevated liver function tests. Computed tomography (CT) showed a huge tumor, 10 cm in diameter, in the right lobe of the liver. The central part of the tumor was consistently un-enhanced, suggesting a large necrotic area. The liver tumor was diagnosed as mucoepidermoid carcinoma by a percutaneous biopsy. Despite chemotherapy with radiation therapy, the tumor showed very aggressive malignancy, resulting in early mortality. We herein report on a rare case of primary mucoepidermoid carcinoma of the liver with pulmonary and lymph node metastasis, confirmed by autopsy, and review the literature.

A sclerosed hemangioma of the liver is an extremely rare type of benign hepatic tumor. A 77-year-old female was referred to Tokushima University Hospital with fever, abnormal liver function tests and a large liver mass. The tumor, 10 x 5 cm in size and located in segment 5-6 of the liver, was depicted as a low density tumor with enhancement by computed tomography (CT). Magnetic resonance imaging (MRI) showed it to be a tumor with a low signal on T1-weighted and a high signal on T2-weighted images. The patient was negative for hepatitis B surface antigen and hepatitis C antibody. She underwent a right hepatectomy for possible malignant liver tumors, including intrahepatic cholangiocarcinoma or fibrolamellar hepatocellular carcinoma. The following histological examination of the surgical specimen revealed the tumor to be a hepatic sclerosed hemangioma with characteristic dense collagenous tissues. We report here on the case of this unusual tumor and review the relevant literature.