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A light-cured intermediate material is useful for fabricating a hard insert and a buffer space mouthguard (HSMG). However, it requires improvement in its mechanical properties and shock-absorbing capacity. The aim of this study was to evaluate the mechanical properties of two prototype light-cured intermediate materials reinforced with glass fibers, and the impact absorption capacity and durability of HSMGs made with the prototype intermediate materials.Two prototype materials containing long and microlength glass fibers in a light-cured intermediate material, Innerframe LC®, for HSMG, were fabricated and tested. A three-point bending test was performed for evaluation of the mechanical properties. In addition, a shock absorption test was conducted using a customized pendulum impact testing machine to evaluate the HSMGs' impact absorption capacity and durability.Long and microlength glass fibers significantly improved flexural modulus and strength. HSMGs made with these two glass fiber-containing materials had high impact absorption capacity against both low and high impact forces, while the mouthguards made with long glass fiber materials had the best results.Long and microlength glass fibers with the prototype materials improved the mechanical properties of Innerframe LC® and the impact absorption capacity and durability of HSMGs. HSMGs made with the long glass fiber prototype materials had the best performance.

Supplementary Figures S1-S2 from Rapid Detection of Epidermal Growth Factor Receptor Mutations in Lung Cancer by the SMart-Amplification Process

Purpose: A positive response to gefitinib in non–small cell lung cancer (NSCLC) has been correlated to mutations in epidermal growth factor receptor (EGFR) gene. Previous reports have been based mainly on diagnostic screening by sequencing. However, sequencing is a time-consuming and complicated procedure, not suitable for routine clinical use.Experimental Design: We have developed rapid, simple, and sensitive mutation detection assays based on the SMart Amplification Process (SMAP) and applied it for analyzing EGFR gene mutations in clinical samples. By using SMAP, we can detect mutations within 30 min including sample preparation. To validate the assay system for potential use in clinical diagnostics, we examined 45 NSCLC patients for EGFR mutations using sequencing and SMAP.Results: The outcomes of the SMAP assay perfectly matched the sequencing results, except in one case where SMAP was able to identify a mutation that was not detected by sequencing. We also evaluated the sensitivity and specificity of SMAP in mutation detection for EGFR. In a serial dilution study, SMAP was able to find a mutation in a sample containing only 0.1% of the mutant allele in a mixture of wild-type genomic DNA. We also could show amplification of mutated DNA with only 30 copies per reaction.Conclusions: The SMAP method offers higher sensitivity and specificity than alternative technologies, while eliminating the need for sequencing to identify mutations in the EGFR gene of NSCLC. It provides a robust and point-of-care accessible approach for a rapid identification of most patients likely to respond to gefitinib.

The purpose of this study was to clarify the effects of jaw-clenching intensity on masseter muscle oxygen dynamics during clenching and recovery and masseter muscle fatigue using the spatially resolved method of near-infrared spectroscopy. Pulse rate, mean power frequency from electromyography in the masseter and visual analogue scale for masseter fatigue were also examined as related items. The 25% and 50% maximum voluntary contractions were determined using electromyography before the experiment and used as visual feedback on the screen. Twenty-three healthy adult male subjects volunteered for this study. Clenching decreased oxygen and oxygenated haemoglobin, and increased deoxygenated haemoglobin in the masseter muscle. The higher the intensity of clenching, the more prominent the effect. The oxygen dynamics tended to return to normal after clenching, but the change was slower with higher clenching intensity. Pulse rate increased with clenching, and the increment was more prominent with higher clenching intensity. Clenching caused a shift of mean power frequency to a lower range, an increase in subjective fatigue, an early appearance of a breakpoint appearance time and a prolongation of a 1/2 recovery time. All of these effects were more evident with increasing clenching intensity. In conclusion, clenching intensity influenced the oxygen dynamics of the masseter muscle and fatigue state during clenching and recovery. The higher the intensity, the greater the impact.

In addition to difficulties with parenchymal resection reflecting anatomic disorientation arising from rotation of the liver remnant that accompanies regeneration, repeat resections typically involve difficult and protracted lysis of adhesions. We describe our technique for facilitating right liver mobilization even in the presence of severe adhesions. Lysis of dense retroperitoneal adhesions posterior to the right liver can be performed safely by incising the diaphragm to facilitate manipulations to mobilize the right liver.

Background: Fucosylated haptoglobin detected by Pholiota squarrosa lectin (PhoSL) that had specificity for fucose alpha 1-6 was reported as an effective biomarker for several gastrointestinal diseases. The aim of this study was to verify Fucosylated haptoglobin detected by Pholiota squarrosa lectin (PhoSL-HP) as a pancreatic cancer (PC) marker using a new method of PhoSL-ELISA. Methods: PhoSL-HP in sera from 98 PC patients and 158 non-PC samples including 32 intraductal papillary mucinous neoplasm (IPMN) patients, 21 chronic pancreatitis (CP) patients and 105 non-pancreatic disease controls (NPDC) were measured. We compared sensitivities, specificities and areas under the curves (AUC) of PhoSL-HP, CA19-9 and CEA as single markers. We also evaluated PhoSL-HP as combination marker by comparing AUC of CA19-9 combined with PhoSL-HP or CEA. Results: The sensitivities of PhoSL-HP, CA19-9 and CEA for PC were 58%, 76% and 42%, respectively. Although the specificity of PhoSL-HP for NPDC was inferior to both of CA19-9 and CEA, that for pancreatic diseases was higher than both of CA19-9 and CEA. Combined CA19-9 with PhoSL-HP, the AUC was significantly higher at 0.880 than single use of CA19-9 at 0.825 in case of distinguishing PC from other pancreatic diseases. In contrast, the AUC of CA19-9 was not elevated significantly when combined with CEA. Conclusion: PhoSL-HP would be a useful marker for PC and have sufficient complementarity for CA19-9. (C) 2019 Published by Elsevier B.V. on behalf of IAP and EPC.

Objective: To assess the safety and efficacy of “polyhedral fenestration technique” (PFT), which we newly developed, in combined hepatectomy and cyst fenestration (CHCF) for symptomatic polycystic liver disease (PLD). Summary of background data: CHCF for PLD has been reportedly less efficacious for its invasiveness because 50% to 70% patients suffered recurrent symptoms after CHCF. Methods: Patient characteristics, intra- and early postoperative variables were compared between 5 PLD patients undergoing CHCF performed with PFT (PLD group) and 95 patients with diseases other than PLD receiving hepatectomy without biliary reconstruction during the same period (Control group) to assess safety of PFT. Chronological changes in total liver volume (TLV) measured by computed tomography (CT) volumetry as well as recurrent symptoms after CHCF were investigated to assess long-term outcomes. Results: Although ≧ Clavien-Dindo grade 2 complications were more common in the PLD group than in the Control group (PLD vs Control, 5/5[100%] vs 27/95[28%], p=0.004), patient characteristics, intra-, and early postoperative variables, including ≧ Clavien-Dindo grade 3 complications, were comparable among the 2 groups. Postoperative observational period of the 5 PLD patients ranged 30 to 88 months with a median of 63. CT volumetry revealed that TLV continued to reduce up to 1 year after surgery and thereafter retained less than 0.5 times of preoperative TLV in all patients. Recurrent liver enlargement or recurrent symptoms were not observed in any of the 5 PLD patients. Conclusions: Although our case series was very small, newly-developed PFT in CHCF for PLD yielded acceptable safety and excellent long-term outcomes.

A right-sided hepatectomy with total caudate lobectomy is indicated for colorectal-cancer liver metastases (CLM) and hepatocellular carcinomas (HCC) located in the caudate lobe with extension to the right lobe of the liver. Caudate-lobe resection (i.e. segmentectomy 1 according to the Brisbane terminology) is one of the most difficult types of hepatectomy to carry out radically and safely. The deep portion of hepatic transection around the caudate lobe, hepatic veins and inferior vena cava is a critical source of massive bleeding. Prolonged transection can increase blood loss.We analyzed the outcome of 10 patients who underwent right-sided hepatectomy with caudate lobectomy using a modified liver hanging maneuver (mLHM) in comparison with 16 patients who underwent the operation without mLHM.Blood loss during liver transection and blood loss per unit area of cut surface were significantly less in the mLHM group (p=0.014 and 0.015, respectively). In patients diagnosed pathologically with liver impairment, transection time was significantly shorter in the mLHM group (p=0.038), as were red blood cell transfusion volume (p=0.042) and blood loss (p=0.049) during transection.Use of mLHM can potentially improve surgical outcomes by reducing blood loss and transection time, which are especially important for patients with liver impairment.

Background We developed 90%-hepatectomized mice that were the fatal model, and analyzed the gene expression profiles using a complementary DNA (cDNA) microarray to clarify the mechanisms of hepatic failure after excessive hepatectomy. Materials and Methods Ribonucleic acid (RNA)s from the remnant hepatic tissue of 70%- and 90%-hepatectomized mice were labeled with fluorescent dyes, and hybridized to the Riken set of 39,168 full-length enriched mouse cDNA arrays. The gene expression profiles in 90%- and 70%-hepatectomized mice were analyzed by scanning date for fluorescent dye signals. Results The down-regulated genes in 90%-hepatectomized mice were genes activating extracellular matrix (ECM) remodeling (matrix metalloproteinases, laminins, and integrins), genes related to cytokines (tumor necrosis factorα converting enzyme, and Janus kinase 3) that were related to the priming, genes related to growth factor (heparin-binding epidermal growth factor-like growth factor and others), and genes promoting cell cycle progression (cyclin D1, D2, and E2) that were related to the progression of hepatocytes. The up-regulated genes were genes inhibiting ECM remodeling [plasminogen activator inhibitors (PAIs)]. Conclusions Hepatic failure after hepatectomy was characterized by the inhibition of hepatic cell cycle priming and progression both induced by ECM remodeling in liver regeneration. Particularly, the overexpression of PAIs was thought to play the major role in the first step of inhibition of ECM remodeling.

症例は60歳代，女性．平成19年夏頃より，約半年毎に右下腹部痛を繰り返し，近医にて虫垂炎と診断され保存的加療で軽快していた．平成21年7月，右下腹部痛出現．近医を受診し血液検査ではWBC 7,700/μl，CRP 1.5mg/dlと炎症所見は軽度であったが，腹部CT検査で虫垂の腫大を認め，当科紹介受診となった．臨床症状は軽快していたが，繰り返す右下腹部痛の既往があり，虫垂炎の術前診断で待機的に虫垂切除術を施行した．虫垂は赤黒色に腫大していたが，粘膜面に肉眼上隆起性病変は認めなかった．病理組織検査では虫垂原発印環細胞癌，切除断端陽性と診断されたため，初回手術後，22日後に開腹下に回盲部切除術（D2）を施行した．術後病理組織診断はsignet-ring cell carcinoma，mp，n0，stageIで現在外来で経過観察中である．虫垂原発印環細胞癌の1例を経験したので文献的考察を加えて報告する．

Background Macrophages play an important role in the initiation of hypercytokinemia, which is involved in the development of liver failure after excessive hepatectomy. This study was aimed at evaluating whether the selective suppression of nuclear factor kappa B (NF-κB) in macrophages by decoy oligodeoxynucleotides (ODN) could prevent liver failure after excessive hepatectomy. Materials and Methods Ninety percent hepatectomy was performed in 8-wk-old mice. NF-κB/decoy/ODN was transfected into the liver by the hemagglutinating virus of Japan-liposome method. The survival rate, serum levels of interleukin (IL)-1β IL-6, and tumor necrosis factor-alpha, and the histological findings in the remnant liver were compared between the 90%-hepatectomized mice transfected with the decoy ODN (decoy group) and the 90%-hepatectomized mice injected with saline (control group). Result The control group mice died within 48 h of the operation, while the survival rate in the decoy group at 48 h after the operation was 35%, and at 2 wk, 15%. The serum levels of all cytokines were significantly lower in the decoy group than in the control group. The number of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling-positive cells in the remnant liver was smaller in the decoy group. Conclusion Transfection of NF-κB/decoy/ODN reduces fatal liver failure in mice after excessive hepatectomy by suppressing hypercytokinemia, but offers only a low rate of survival.

Few details of the clinical features of hepatocellular carcinoma (HCC) developing extrahepatic recurrence after a curative resection have been published. The purpose of this study was to clarify the clinicopathologic findings of patients with HCC who experienced extrahepatic metastases.Clinicopathologic data were available for 119 patients who underwent an R0 resection for HCC. Twenty-three patients who developed extrahepatic metastases during the follow-up period were compared with the patients who remained free from recurrence for at least 5 years after resection (n = 21) or with only intrahepatic recurrences (n = 75).Patients with extrahepatic recurrences were more likely to have their tumor macro- or microscopically invading the tumor capsule (P0.001) and hepatic vein (P = 0.003), a high AFP concentration (P = 0.014), and advanced TNM stage (P = 0.006) than the other patients. As for treatment-related variables, inflow vessel occlusion during hepatectomy was less frequently associated with extrahepatic recurrences than if it were not performed (P0.001). By multivariate analysis, absence of tumor invasion to the capsule (relative risk [RR] = 0.080; P = 0.023) or to the hepatic vein (RR = 0.108; P = 0.014) and a hepatectomy in which inflow vessel occlusions were performed (RR = 0.161; P = 0.004) were selected as independent factors for reducing extrahepatic recurrences after a hepatectomy.In HCC patients, the control of intrahepatic recurrences and extrahepatic recurrences after a hepatectomy is important to improve the prognosis. Inflow occlusion during the hepatectomy may reduce HCC metastases to extrahepatic sites.

Background/Aim Prostaglandin E 1 (PGE 1 ) has a wide-ranging effect on cytoprotection. Overproduction of heat shock protein 70 (HSP70) in the liver protects hepatocytes under various pathologic conditions. In this study, we examined the effect of a nontoxic HSP-inducer, PGE 1 , on acute liver failure after 95% hepatectomy in rats. Methods PGE 1 or vehicle was intravenously administered to rats 30 min before and during hepatectomy. Results Nine of 30 rats pretreated with PGE 1 survived, whereas all 20 rats pretreated with vehicle died within 96 h after operation. During the 24-h postoperative period, PGE 1 significantly suppressed the release of alanine aminotransferase and elevation of hyaluronic acid. Histological examination showed that the vacuolized hepatocytes and round hepatocytes with pyknotic nuclei are frequently seen in rats pretreated with vehicle, whereas active regeneration is seen in rats pretreated with PGE 1 . During the first 24 h after surgery, HSP70 induction was absent in the residual livers of vehicle-treated rats. In contrast, PGE 1 stimulated the HSP accumulation within 24 h, and viable hepatocytes contained abundant HSP70 in their nuclei. Conclusion Our results suggest that PGE 1 may prevent acute liver failure after massive hepatectomy, at least in part, by enhancing HSP70 production in the residual liver.

Purpose: Aberrant activation of epidermal growth factor receptors (EGFR/HER1) by ligand stimulation or heterodimerization with human epidermal growth factor 2 (HER2) is considered to play an important role in the development of colorectal carcinoma. Amphiregulin (AR) is a ligand of EGFR that might be related to the development and progression of gastrointestinal tumors. The aim of this study was to determine the AR, EGFR, and HER2 protein expression levels and to evaluate their prognostic relevance to the clinical course of colorectal cancer. Experimental Design: The AR, EGFR, and HER2 protein levels in primary tumors of colorectal cancer (n = 106) were examined using immunohistochemistry. Metastatic sites in liver specimens (n = 16) were also analyzed in the same manner. Results: Thirteen (81.6%) metastatic lesions of the liver stained positive for AR. Among the primary lesions of colorectal cancer, 58 (54.7%) stained positive for AR, 13 (12.3%) stained positive for EGFR, and 5 (4.7%) stained positive for HER2. When the relationships between each protein expression level and the clinicopathologic factors were examined, only the AR expression level was significantly related to liver metastasis (P = 0.0296). A multivariate analysis of liver metastasis proved that AR expression was an independent prognostic factor of liver metastasis from colorectal cancer (P = 0.0217). Conclusions: AR expression in primary lesions of colorectal cancer is an important predictive marker of liver metastasis.

Background/Aims: Nitric oxide synthase 2 (NOS2) is expressed during liver regeneration after a partial hepatectomy (PHx); NOS2 subsequently synthesizes nitric oxide (NO). However, the role of NOS2-synthesized NO in post-PHx liver regeneration remains unclear. We investigated the role of NOS2-synthesized NO in liver regeneration. Methods: NOS2 knockout (NOS2-KO) mice and control mice were subjected to PHx. Liver mass recovery and serum alanine aminotransferase (ALT) levels were then evaluated. The expressions of Ki-67 and single-strand DNA were also evaluated in remnant liver specimens. Differences in the gene expression profiles of the two groups of remnant liver specimens were analysed using a microarray and were validated using a reverse transcription-polymerase chain reaction (RT-PCR). Results: In NOS2-KO mice, liver regeneration was delayed and apoptosis and serum ALT levels were higher than the levels in the control mice. A microarray study and RT-PCR revealed that heat shock protein 70 family (HSP70 family), haeme oxygenase 1 (Hmox1), neuropilin 1 (Nrp1) and epidermal growth factor receptor (EGFR) were downregulated in NOS2-KO mice. Conclusions: NOS2-synthesized NO may improve hepatocyte viability through the induction of the HSP70 family and Hmox1 and may sensitize the remnant liver to growth factors through the induction of Nrp1 and EGFR post-PHx.

Although retrospective studies have demonstrated survival benefit from hepatectomy for metastatic colorectal cancer, few studies have examined patients with multiple bilobar metastases to identify survival-related factors throughout their course.Among 277 patients with R0 resection for liver metastases from colorectal cancer, 79 patients had 4 or more lesions in a bilobar distribution. To determine impact on long-term outcome, we compared clinicopathologic factors retrospectively between 3-year survivors and patients who died less than 3 years after hepatectomy.Among 79 patients with 4 or more bilobar metastases, 5 patients (6.3%) attained prolonged remission after initial hepatectomy. By multivariate analysis, a lack of adjuvant chemotherapy compromised survival (relative risk or RR, 2.21; P = .036), as did prehepatectomy carcinoembryonic antigen exceeding 12 ng/mL (RR, 2.12; P = .039). Treatment-related variables such as repeat resections in the event of liver recurrence (P.01) or lung metastases (P.05), as well as adjuvant chemotherapy (P.01), differed significantly between 3-year survivors and nonsurvivors, as did the differences in number of metastases, maximum size of metastases, concomitant extrahepatic metastases at the time of initial hepatectomy, and disease-free interval preceding initial recurrence.Although not effective as a sole treatment for multiple hepatic metastases of colorectal cancer, liver resection is important in multimodal therapy. Reoperations for recurrence of metastases, followed by additional chemotherapy, frequently obtained long survival.

症例は59歳の男性で, 糖尿病の加療目的で入院中, 腹部CTで膵頭部に嚢胞性腫瘤を指摘された. 画像上, 膵頭部の分枝型IPMCの診断で膵頭十二指腸切除術を施行した. 病理組織学的診断は微小浸潤型IPMCで切除断端は癌陰性であった. 術後4か月目から腫瘍マーカーの上昇を認め, 6か月目の腹部CTで残膵に3cm大の腫瘍を認めたため, 残膵癌の診断で残膵全摘を施行した. 病理組織は高度な脈管浸潤を伴った中分化型管状腺癌で, 癌とその周囲組織ともに膵管内の腺腫成分や乳頭状増殖は認めず, 全切片で浸潤型発育を示していた. また, 初発IPMCではMUC1陽性, MUC2陽性でK-ras変異陰性であったのに対し, 残膵浸潤癌ではMUC1陽性, MUC2陰性, K-ras変異陽性であった. 以上より, 本症例におけるIPMCと残膵浸潤癌の発生源は異なるものと考えられた.

Transcriptional initiation is a key step in the control of mRNA synthesis and is intimately related to chromatin structure and histone modification. Here, we show that the ubiquitylation of H2A (ubH2A) correlates with silent chromatin and regulates transcriptional initiation. The levels of ubH2A vary during hepatocyte regeneration, and based on microarray expression data from regenerating liver, we identified USP21, a ubiquitin-specific protease that catalyzes the hydrolysis of ubH2A. When chromatin is assembled in vitro, ubH2A, but not H2A, specifically represses the di- and trimethylation of H3K4. USP21 relieves this ubH2A-specific repression. In addition, in vitro transcription analysis revealed that ubH2A represses transcriptional initiation, but not transcriptional elongation, by inhibiting H3K4 methylation. Notably, ubH2A-mediated repression was not observed when H3 Lys 4 was changed to arginine. Furthermore, overexpression of USP21 in the liver up-regulates a gene that is normally down-regulated during hepatocyte regeneration. Our studies revealed a novel mode of trans-histone cross-talk, in which H2A ubiquitylation controls the di- and trimethylation of H3K4, resulting in regulation of transcriptional initiation.

Background/Aims Well-organized turnover of the extracellular matrix is important in liver regeneration, which is regulated by the plasminogen activating system. The aim of this study was to investigate the role of plasminogen activator inhibitor-1 (PAI-1) after excessive hepatectomy and to ascertain whether angiotensin-converting enzyme (ACE) inhibitors, which are PAI-1 inhibitors as well, successfully improve the survival rate of rats that have undergone 95% partial hepatectomy (PHx). Methods Using liver tissues sampled after 90% or 95% PHx, the expression of PAI-1 mRNA was evaluated using reverse transcription polymerase chain reaction. Hepatic PAI-1 protein and urokinase-type plasminogen activator (uPA) levels were determined by enzyme-linked immunosorbent assay. Survival study and cytodynamic analysis by 5-bromo-2′-deoxyuridine staining were performed to evaluate the effects of ACE inhibition. Results The levels of PAI-1 mRNA and hepatic PAI-1 protein in the 95% PHx group peaked and were then maintained. By contrast, the uPA level fell relative to the 90% PHx group. Additionally, the hepatic PAI-1 protein level decreased and the survival rate improved in the 95% PHx rats that had undergone ACE inhibition. Conclusions Our experimental results suggest that PAI-1 plays a role in the occurrence of liver failure after excessive hepatectomy via accelerated maturation of pro-uPA and fibrinolytic factors. These are potential molecular therapeutic targets for liver failure after excessive hepatectomy.

Background and Aim: Post-hepatectomy infections require careful attention, because they may deteriorate into liver failure. We retrospectively reviewed such infections in cases without biliary or intestinal reconstruction. Methods: This retrospective study involved 535 patients with liver tumors who underwent hepatectomy at the Department of Gastroenterological Surgery of Yokohama City University Hospital between April 1992 and March 2005. After classification into four groups depending on changes in infection countermeasures used during different periods, the treatment outcomes were examined. No such anti-infection measures were taken during the first period; a closed suction drainage system and early enteral nutrition after surgery were introduced between the first and second periods; thorough management of bile leakage and prevention of nosocomial infection were added between the second and third periods; and surgical site infection (SSI) surveillance together with absorbable sutures instead of silk sutures between the third and fourth periods. Results: The incidence of postoperative infection decreased significantly with additional countermeasures: first period 44.7%; second period 24.1%; third period 15.0%; and fourth period 9.2%. The incidence of both SSI and remote infection were similarly reduced. Postoperative infection risk factors were age, presence of diabetes mellitus, the use of silk sutures and bile leakage, while those for SSI were the use of silk sutures and bile leakage. Conclusion: The incidence of postoperative infection and SSI were significantly reduced by our infection countermeasures, especially by bile leakage management and the use of absorbable sutures.

A key feature of the smart amplification process version 2 (SMAP-2) is the ability to suppress mismatch amplification by using a unique asymmetric primer design and Thermus aquaticus MutS (Taq MutS). However, we report here that use of SMAP-2 for polymorphism determination of the UGT1A1*28 allele required a further ancillary approach for complete background suppression. The UGT1A1*28 allele is a microsatellite copy number polymorphism. This is the first reported SMAP-2 assay designed for genotyping genetic variations of microsatellites. We found that by the addition of a primer to the amplification reaction, called a competitive probe (CP), assay specificity could be significantly enhanced. Including sample preparation time and use of a CP-enhanced SMAP-2 assay, we could rapidly detect the UGT1A1*28 polymorphism within 60 min. To test our method, we compared results from PCR sequencing and the CP-enhanced SMAP-2 assay on 116 human blood samples for UGT1A1*28 polymorphism and demonstrated perfect concordance. These results illustrate the versatility of SMAP-2 for molecular diagnostics and provide a new approach for enhancing SMAP-2 assay specificity.

We evaluated the usefulness of synthetic absorbable sutures (Vicryl) in preventing surgical site infection (SSI) after hepatectomy. A rat model of 60% partial hepatectomy was used. Bleeding from the cut surface of the liver was controlled by using two suture types: silk and Vicryl. In the Vicryl group, the lesser omentum was slightly adherent to the cut surface of the liver, while in the silk group, the suture remained, and severe adhesions were found. The number of Staphylococcus aureus was significantly larger in the silk group. We compared a group of patients (n = 125) who underwent hepatectomy using silk with one (n = 188) using Vicryl. The respective incidences of SSI and infection on the cut surface of the liver in the Vicryl group (3.2, 1.6%) were significantly lower than in the silk group (11.2, 8.8%). In accordance with the results of multivariate analysis, duration of operation, use of silk sutures and the complication of bile leakage were selected as independent factors. The risk of SSI in the silk group was 3.4 times that in the Vicryl group. The use of synthetic absorbable sutures, instead of silk sutures, in all the procedures of hepatectomy contributed significantly to the prevention of SSI.

Purpose: A positive response to gefitinib in non–small cell lung cancer (NSCLC) has been correlated to mutations in epidermal growth factor receptor (EGFR) gene. Previous reports have been based mainly on diagnostic screening by sequencing. However, sequencing is a time-consuming and complicated procedure, not suitable for routine clinical use. Experimental Design: We have developed rapid, simple, and sensitive mutation detection assays based on the SMart Amplification Process (SMAP) and applied it for analyzing EGFR gene mutations in clinical samples. By using SMAP, we can detect mutations within 30 min including sample preparation. To validate the assay system for potential use in clinical diagnostics, we examined 45 NSCLC patients for EGFR mutations using sequencing and SMAP. Results: The outcomes of the SMAP assay perfectly matched the sequencing results, except in one case where SMAP was able to identify a mutation that was not detected by sequencing. We also evaluated the sensitivity and specificity of SMAP in mutation detection for EGFR. In a serial dilution study, SMAP was able to find a mutation in a sample containing only 0.1% of the mutant allele in a mixture of wild-type genomic DNA. We also could show amplification of mutated DNA with only 30 copies per reaction. Conclusions: The SMAP method offers higher sensitivity and specificity than alternative technologies, while eliminating the need for sequencing to identify mutations in the EGFR gene of NSCLC. It provides a robust and point-of-care accessible approach for a rapid identification of most patients likely to respond to gefitinib.

Two-stage hepatectomy aims to minimize liver failure risk by performing a second resection after regeneration, assuming that remnant liver hypertrophy after the second resection is similar to that seen in repeat hepatectomy, yet the impact of a two-stage strategy on liver volume and function remains to be demonstrated.Twenty patients undergoing two-stage hepatectomy for multiple colorectal cancer metastases and 21 patients with more than two sections of liver parenchyma totally removed by repeat liver resections for recurrence were enrolled. Liver volumes after final hepatectomy and postoperative liver function were compared.Median total liver volumes before initial hepatectomy and after final hepatectomy of multiple resections were 942 and 863 ml in patients with repeat hepatectomy, whereas volumes at corresponding time points were 957 and 777 ml in patients with two-stage hepatectomy. The ratio of total liver volume after both hepatectomies to preoperative volume in the two-stage group (81.7%) was lower than that in the repeat resection group (92.0%, P = 0.027). Greater aspartate aminotransferase and prothrombin time and lower platelet count 1 month postoperatively and lower albumin at 6 months were evident after two-stage hepatectomy compared with repeat hepatectomy.Two-stage hepatectomy is characterized by diminished hepatic regenerative capacity and postoperative liver function.

We investigated the risk of morbidity after repeat resections for liver recurrence of hepatocellular carcinoma or for colorectal liver metastases.Although repeat hepatectomy for recurrences of hepatocellular carcinoma or for colorectal cancer liver metastases is well known only to carry risks similar to those seen for an initial liver resection, the safety of such a procedure is questionable because, typically, only a few liver tumors are thought suitable for repeat hepatectomy.Clinicopathology data were available for 412 hepatectomy patients (hepatocellular carcinoma in 226, colorectal liver metastases in 186). Risk factors for postoperative complications were analyzed retrospectively among the 57 patients undergoing a repeat hepatectomy.Using multivariate analysis, intraoperative blood loss (relative risk, 9.61; P = 0.02) affected the occurrence of postoperative complications after a second hepatectomy. In patients who lost more than 1.29 l blood intraoperatively at the second hepatectomy, a major hepatectomy (P0.05) by means of an anatomical type of resection (P0.01) was more often performed than in the patients with 1.29 l or less of blood loss.The major independent risk factor associated with complications after a second hepatectomy for liver recurrence was intraoperative blood loss. The extent of liver resection, especially in an anatomical manner, directly influences the amount of blood loss.

Accurate knowledge of partial anatomy is essential in hepatic surgery but is difficult to acquire. We describe the potential impact of a new technique for constructing three-dimensional virtual images of the portal vein, hepatic artery, and bile ducts and present a representative case. An 80-year-old man was suspected of having papillary cholangiocarcinoma arising in S8 of the liver and extending to the hepatic hilum intraluminaly. Right hemihepatectomy with bile duct resection was planned. However, it was uncertain whether duct-to-duct biliary reconstruction would be possible based on the appearance of the confluence of the right and left hepatic ducts on cholangiogram and conventional computed tomograph. Virtual three-dimensional images of the liver were constructed and revealed vascular and biliary anatomy. They showed that the upper margin of bile duct excision would be 19 mm from the umbilical point of the left portal vein, and that the site of the left branch of the caudate lobe bile duct could be preserved. Based on this information, we performed a sphincter-preserving biliary operation safely without complications. Planning complex biliary surgery may be improved by the use of virtual three-dimensional images of the liver. This approach is especially useful in candidates for postoperative regional chemotherapy.

Massive arterial hemorrhage is, although unusual, a life-threatening complication of major pancreatobiliary surgery. Records of 351 patients who underwent major surgery for malignant pancreatobiliary disease were reviewed in this series. Thirteen patients (3.7%) experienced massive hemorrhage after surgery. Complete hemostasis by transcatheter arterial embolization (TAE) or re-laparotomy was achieved in five patients and one patient, respectively. However, 7 of 13 cases ended in fatality, which is a 54% mortality rate. Among six survivors, one underwent selective TAE for a pseudoaneurysm of the right hepatic artery (RHA). Three patients underwent TAE proximal to the proper hepatic artery (PHA): hepatic inflow was maintained by successful TAE of the gastroduodenal artery in two and via a well-developed subphrenic artery in one. One patient had TAE of the celiac axis for a pseudoaneurysm of the splenic artery (SPA), and hepatic inflow was maintained by the arcades around the pancreatic head. One patient who experienced a pseudoaneurysm of the RHA after left hemihepatectomy successfully underwent re-laparotomy, ligation of RHA, and creation of an ileocolic arterioportal shunt. In contrast, four of seven patients with fatal outcomes experienced hepatic infarction following TAE proximal to the PHA or injury of the common hepatic artery during angiography. One patient who underwent a major hepatectomy for hilar bile duct cancer had a recurrent hemorrhage after TAE of the gastroduodenal artery and experienced hepatic failure. In the two patients with a pseudoaneurysm of the SPA or the superior mesenteric artery, an emergency re-laparotomy was required to obtain hemostasis because of worsening clinical status. Selective TAE distal to PHA or in the SPA is usually successful. TAE proximal to PHA must be restricted to cases where collateral hepatic blood flow exists. Otherwise or for a pseudoaneurysm of the superior mesenteric artery, endovascular stenting, temporary creation of an ileocolic arterioportal shunt, or vascular reconstruction by re-laparotomy is an alternative.

Although the usefulness of antimicrobial prophylaxis for clean-contaminated surgery has been recognized, only a few randomized controlled studies on the duration of administration after hepatectomy have been performed. We investigated the duration of antimicrobial prophylaxis after hepatectomy.The subjects were 180 patients who underwent hepatectomy without reconstruction of the biliary or intestinal tract between April 2003 and March 2006 at our department. The patients were randomly allocated to groups to be treated with flomoxef sodium as antimicrobial prophylaxis for 2 days (89 patients) or 5 days (91 patients), including the operation day. The presence or absence of systemic inflammatory response syndrome (SIRS) and infections was investigated.No significant differences were noted in patient background between the two groups. Infections occurred in seven and six patients in the 2 day and 5 day treatment groups (7.9% and 6.6%), respectively, showing no significant difference between the two groups. No significant difference was noted when the cases were divided into surgical site infections and remote infections. The positive rate of SIRS was significantly higher in the 2 day treatment group than in the 5 day treatment group on days 2 and 3 after surgery. The risk factors in patients who developed infections were blood loss, operation time and the complication of biliary fistula.Two day administration of flomoxef sodium may be sufficient for antimicrobial prophylaxis after hepatectomy. However, when SIRS is positive on post-operative day 2, and induction of liver failure is of concern, it may be safer to continue antimicrobial drug administration until SIRS is eliminated.

We investigated efficacy of microwave ablation plus hepatectomy for multiple colorectal liver metastases. Clinicopathologic data were analyzed retrospectively for 71 consecutive patients with four or more bilobar liver metastases from colorectal cancer who underwent hepatectomy with or without microwave ablation. Overall, no significant differences were found and as well as disease-free survival between 19 patients with resection/ablation and 52 patients with resection (p = 0.18 and 0.93). Multivariate analysis selected prehepatectomy carcinoembryonic antigen concentration in serum as an independent prognosticator for survival (p = 0.04), but not resection/ablation vs. resection. In the patients with combined resection/ablation, recurrences occurred near the resection or ablation line in only 3 patient (30%, although multiple tumors (≥ 4) were the most common liver recurrence pattern (60%). Microwave ablation plus hepatic resection expanded indications for surgery to treat multiple bilobar liver metastases.

We investigated clinical characteristics and surgical outcome of hepatocellular carcinoma in association with hepatitis viral status. No consensus exists concerning differences in surgical outcome in patients with hepatocellular carcinoma according to viral hepatitis status, especially those negative for hepatitis B virus surface antigen and antibody to hepatitis C virus. Clinicopathologic data were available for 39 hepatectomy patients with hepatocellular carcinoma who were negative for hepatitis B virus surface antigen and hepatitis C virus antibody. Clinical characteristics and surgical outcome were analyzed retrospectively and compared to those patients with positive hepatitis viral markers. Patients negative for viral hepatitis markers were more likely to have large, advanced-stages tumors with relatively well-preserved liver function and had a lower incidence of intrahepatic recurrences (P = 0.009). The intrahepatic recurrence rate reached a plateau at approximately 3 years after resection in patients with negative viral markers, while it continued to increase steadily in patients positive for viral hepatitis markers. By multivariable analysis, the absence of viral hepatitis markers predicted a decreased rate of intrahepatic recurrence (relative risk, 0.222; P = 0.001). Adequate surgical resection in hepatocellular carcinoma patients negative for viral markers offers a good survival benefit, regardless of the etiology of the hepatocellular carcinoma.

We report a rare case of porcelain gallbladder associated with pancreas divisum (PD). A 60-year-old woman suffered from discomfort in the back of the right side. An abdominal radiograph revealed a calcified spherical mass in the right upper quadrant. Ultrasonography revealed a scattered echo with a posterior acoustic shadow in the gallbladder wall. A plain computed tomography (CT) scan showed flecks of intramural calcification in the wall of the gallbladder. Endoscopic retrograde cholangiopancreatography (ERCP) and magnetic resonance cholangiopancreatography (MRCP) showed separate openings for the Santorini and Wirsung ducts. The patient underwent cholecystectomy after porcelain gallbladder and pancreas divisum had been diagnosed. The porcelain gallbladder resulted from a stone impacted in the neck of the gallbladder. Patients with PD should be followed carefully, because gallstones often accompany PD, and porcelain gallbladder may result, as in this patient.

To clarify the role of the middle hepatic vein (MHV) in liver regeneration of the remnant liver after right hemihepatectomy for hepatic tumors, we reviewed 29 patients to evaluate liver regeneration for up to 12 postoperative months.Volume regeneration of the remnant liver was investigated by computed tomography at 3, 6, and 12 postoperative months. The remnant liver was divided into the following three areas: the medial section (segment IV), the lateral section (segments II and III), and segment I. The patients were divided into two groups: group A (n = 17), in which the MHV was preserved in the remnant liver, and group B (n = 12), in which the MHV was removed.Volume regeneration of each area continued until 6 postoperative months but did not increase thereafter. On univariate analysis, differences in the volume regeneration of each area between the groups were not significant at any measured time point. Furthermore, disruption of the MHV was determined to not be crucial to the volume regeneration of any liver area on multivariate analysis. Only the resection volume (percentage) significantly affected liver regeneration of the remnant liver.Disruption of the MHV does not decisively affect liver regeneration of remnant liver after right hemihepatectomy for hepatic tumors.

To determine whether or not the Milan criteria (MC) should be used to determine the applicability of liver transplantation (LT) as a first-line treatment for patients with cirrhosis with hepatocellular carcinoma (HCC) who are able to endure hepatectomy.Retrospective analysis of 82 patients with cirrhosis with HCC who were treated by hepatectomy without LT at our institution between 1990 and 2003.Of these 82 patients, 48 met the MC. Proportional hazard regression analyses to determine the independent prognostic factors for postoperative cumulative patient and disease-free survival showed that meeting the MC is the strongest prognostic factor for both patient and disease-free survival. The cumulative patient and disease-free survival rates were 76.7% and 28.9%, respectively, at 5 years in patients who met the MC. The cumulative disease-free survival was markedly inferior to those in previously reported series of LT for HCC who met the MC, but the cumulative patient survival was comparable to those in the previously reported series. A comparison of cumulative postoperative survival between patients who met the MC and fulfilled all five factors listed below and patients who met the MC but did not fulfill any of the five factors demonstrated that the latter patients showed statistically significantly worse postoperative patient survival than the former. The five factors included: Model for End-Stage Liver Disease score10, indocyanine green retention rate at 15 minutes20%, absence of microscopic fibrous capsular invasion and microscopic intrahepatic metastases, and earlier grade (T1 or T2) of American Joint Committee on Cancer tumor classification.The MC should not be used to determine the applicability of LT as a first-line treatment for patients with HCC considered able to endure hepatectomy. However, modifying MC with some clinicopathological factors could satisfy the appropriate criteria for applying LT as a first-line treatment for these patients.

Objectives To select an appropriate treatment regimen, it is essential to accurately characterize the nature of a thrombus. This study prospectively assessed the ability of contrast-enhanced sonography to differentiate between benign and malignant portal vein thrombosis in a population of high-risk patients. Methods Fifty-five patients (43 men and 12 women; mean age, 66 years; range, 55-83 years) with thrombi of the portal venous system were examined by power Doppler sonography and contrast-enhanced sonography with the intravenous contrast agent SH U 508A (Levovist; Schering AG, Berlin, Germany). Of the thrombi, 40 were characterized as malignant and 15 as benign. Pulsatile flow in the thrombus on power Doppler sonography and positive enhancement of the thrombus on contrast-enhanced sonography were judged as indications of a malignant thrombus. The sensitivity and specificity of both methods in differentiating the nature of the thrombus were evaluated. Results The detection of pulsatile flow in a portal vein thrombus as the criterion for diagnosing malignant portal vein thrombus yielded overall sensitivity of 82.5% and specificity of 100%, whereas positive enhancement of the portal vein thrombus itself as a criterion for diagnosing malignancy yielded overall sensitivity and specificity of 100% for each. Conclusions Contrast-enhanced sonography can be helpful in discriminating between benign and malignant portal vein thrombi.

The aim of this study was to assess the prognostic impact of the number of lymph node metastases. The medical records of 33 patients with node-positive gallbladder cancer (GBC) treated at our institution from January 1985 through December 2002 were reviewed. There were 10 cases with a single node metastasis. The sites were as follows: the cystic duct node, the pericholedochal node, the retroportal node, the hilar node, the lymph node around the common hepatic artery, and the paraaortic node. According to the International Union Against Cancer (UICC) 5th edition, 5-year survival rates for the patients with pN1, pN2, and greater than pN2 were 19.2%, 10%, and 0%, respectively (not significant). Patients with a single node metastasis had a higher 5-year survival rate (33%) than patients with two or more lymph node metastases (0%; P < 0.05). There were no lymph node recurrences in patients with a single node metastasis. Number of positive nodes and liver metastasis were factors predictive of significantly worse survival. Rather than using the topographic classification, or even simply classifying whether nodal involvement is positive or negative, classification according to the number of positive nodes will contribute to establishing a more practically useful staging system.

Introduction: The aim of the present study was to determine whether rats with moderately fatty liver could withstand a 90% hepatectomy, which rats with normal livers can survive. Material and Methods: Nine-week-old male Wistar rats were used. Normal rat chow was fed to the normal liver group, and fat-enriched rat chow was fed to the fatty liver group for 4 weeks to induce a moderately fatty liver. The authors have previously reported that this fatty liver rat model can cause fatal liver dysfunction after reduced-size-liver transplantation. A 90% and 95% hepatectomy were performed using rats of both groups to evaluate posthepatectomized liver function. Results: All rats undergoing a 90% hepatectomy were still alive 30 days after the hepatectomy, but the rats that underwent a 95% hepatectomy were all dead within 4 days regardless of group. Increases in the liver remnant wet weight measured until 7 postoperative days after 90% hepatectomy were almost similar among the two groups. Alanin aminotransferase measured at 24, 48, 72, and 168 h after a 90% hepatectomy were significantly higher in the fatty liver group than in the normal liver group. Similarly, at up to 72 h postoperatively, the serum hyarulonic acids were significantly higher in the fatty liver group. Conclusion: A moderately fatty liver did not cause mortality in 90% hepatectomized rats. However, it caused a higher degree of hepatic parenchymal as well as sinusoidal injury.

Background We investigated the efficacy of microwave ablation plus hepatectomy for multiple bilobar colorectal metastases to the liver. No consensus exists concerning local ablation plus hepatic resection for treating multiple bilobar colorectal liver metastases, partly because of a lack of long-term comparative survival data. Methods Clinicopathologic data were analyzed retrospectively for 53 consecutive patients with 5 or more bilobar liver metastases from colorectal cancer who underwent hepatectomy with or without microwave ablation. Outcome measures were recurrence rate, recurrence pattern, and survival. Results Combined resection/ablation was performed more frequently in patients with more liver metastases ( P = .03). No significant differences were found for overall, disease-free, or hepatic recurrence–free survival between 16 patients with resection/ablation and 37 patients with resection ( P = .43, .54, and .86, respectively). Multivariate analysis selected prehepatectomy carcinoembryonic antigen concentration in serum as an independent prognosticator for survival ( P = .02), but not resection/ablation versus resection. In patients with combined resection/ablation, recurrence occurred near the resection or ablation line in only 2 patient (22%), whereas multiple neoplasms (≥4) was the most common liver recurrence pattern (78%). Conclusions Microwave ablation plus hepatic resection expanded indications for operation to treat multiple bilobar liver metastases, with survival similar to that in less-involved hepatic resection patients.

胆嚢摘出術の術後胆汁漏の原因として副肝管および異所性肝内胆管末梢枝の損傷などが報告されている.今回腹腔鏡下胆嚢摘出術の際に確認された胆汁漏に対する検索でLuschka管を確認できた1例を経験したので報告する.症例は61歳,男性.胆嚢結石に対し腹腔鏡下胆嚢摘出術施行.術後麻酔からの覚醒時にドレーンから胆汁様排液を認めた.再気腹し検索したところ胆嚢管断端や総胆管からの胆汁瘻は認めずLuschka管を認めた.開口部をクリップを用いて閉鎖した.胆嚢摘出の際,手術は胆嚢側に沿って行い,索状組織がある場合にはクリップをかけて切離することが肝要であり,異所性胆管たとえばLuschka管,副肝管,異所性肝内胆管末梢枝などの存在も念頭に置く必要があると考えられた.

Recent advances have extended indications for hepatectomy to include multiple bilobar colorectal liver metastases (CLM). Staging systems based on the biological malignancy of primary and metastatic tumors provide appropriate indications for hepatectomy in CLM. However, suitability for resection in patients with complex and extensive hepatic metastases is controversial.A medline search was performed to identify papers reporting the resection for CLM. Techniques, indication, and results were reviewed.If the anticipated remnant liver volume is small (25-40% of total), suggesting a high risk of postoperative liver failure, portal vein embolization (PVE) is recommended prior to hepatectomy. However, curative resections are not always possible. Specifically in synchronous multiple bilobar CLM, two-stage hepatectomy, comprising bilateral hepatectomy and primary resection with or without PVE, can prevent growth of ipsilateral metastatic nodules in the remnant liver and reduce surgical risk. Several local ablation techniques can complement surgery if hepatic resection alone increases the risk of postoperative liver failure or is not curative. Chemotherapy combined with targeted treatment can suppress recurrence and extend indications for hepatectomy by reducing the size and number of primary irresectable tumors.PVE or staged procedure combining with local ablation or neoadjuvant, downstaging or adjuvant therapies extends indications for hepatectomy to include multiple bilobar CLM. The 5-year survival rate for multiple bilobar CLM treated with alternating hepatectomy and chemotherapy is comparable to the values reported for single and hemilateral CLM.

Background The aim of this study was to evaluate the impact of patient age on surgical therapy for colorectal liver metastases. Study design Between 1992 and 2004, 212 consecutive patients underwent potentially curative hepatic resection. Sixty-two patients were 70 years or older at the time of resection (older group) and 150 patients were less than 70 years at the time of resection (younger group). Results A proportion of older patients had a history of severe cardiopulmonary disease (32.3%) and respiratory insufficiency (6.5%). Intraoperative variables, such as resected liver volume, operation time, estimated blood loss, and blood transfusion, were not notably different between older and younger patients. Postoperative complications after resection occurred in 19.7% of older patients and at a similar rate (23.3%) in the younger group. Resection mortality was 0% in older patients and 0.49% in younger patients. The 5-year survival rates of older and younger patients were 34.1% and 53.1%, respectively. Compared with younger patients, the overall survival rate of older patients was markedly lower (p Conclusions Advanced chronologic age cannot be regarded as a medical contraindication for hepatic resection of colorectal liver metastases in patients who are more than 70 years of age.

Prostaglandin E1 (PGE1) has several potential therapeutic effects, including cytoprotection, vasodilation, and inhibition of platelet aggregation. This study investigates the protective action of PGE1 against hepatic ischemia/reperfusion injury in vivo using a complementary DNA microarray. PGE1 or saline was continuously administered intravenously to mice in which the left lobe of the liver was made ischemic for 30 minutes and then reperfused. Livers were harvested 0, 10, and 30 minutes postreperfusion. Messenger RNA was extracted, and the samples were labeled with two different fluorescent dyes and hybridized to the RIKEN set of 18,816 full-length enriched mouse complementary DNA microarrays. Serum alanine aminotransferase and aspartate aminotransferase levels at 180 minutes postreperfusion were significantly lower in the PGE1-treated group than in the saline-treated group. The cDNA microarray analysis revealed that the genes encoding heat-shock protein (HSP) 70, glucose-regulated protein 78, HSP86, and glutathione S-transferase were upregulated at the end of the ischemic period (0 minutes postreperfusion) in the PGE1 group. Our results suggested that PGE1 induces HSPs immediately after ischemia reperfusion. HSPs might therefore play an important role in the protective effects of PGE1 against ischemia/reperfusion injury of the liver.

The objective of this study was to evaluate the effectiveness and feasibility of using the Cavitron ultrasonic surgical aspirator (CUSA) with argon beam coagulation (ABC) during hepatic resection, in comparison with a conventional method using CUSA with bipolar cautery. Between April 2003 and March 2004, a series of 14 consecutive patients underwent hepatic resection of normal liver. Hepatectomies were performed using CUSA and bipolar irrigation electrocautery (BP) in eight patients between April 2003 and December 2003. CUSA and an ABC were used in six patients between January 2004 and March 2004. There were no differences in patient characteristics between the two groups. Blood loss per area of transected liver surface was significantly lower for CUSA with ABC than for CUSA with BP (2.9 +/- 1.44 vs. 6.33 +/- 3.14 ml/cm2). Furthermore, the speed of resection, defined as resection time per area of transected liver surface, was significantly greater for CUSA with ABC than for CUSA with BP (0.53 +/- 0.14 vs. 2.18 +/- 1.73 min/cm2). This new technique of combining CUSA with ABC can decrease blood loss during hepatic parenchymal transection and shorten the resection time.

Objective Nutritional disturbances such as ascites and hypoalbuminemia frequently arise after hepatectomy for liver cancer with liver cirrhosis. We examined the possibility of maintaining a favorable state of nutrition by outpatient administration of branched-chain amino acid (BCAA) granules. Methods Forty-three patients who had gross liver cirrhosis complicated by liver cancer and underwent surgery up to May 2002 were given BCAA granules (n = 21, BCAA group) or no granules (n = 22, control group). Results 1) Background details such as age, sex, surgical technique, blood loss, and duration of surgery showed no significant differences. 2) Among objective findings, improvement of ascites and edema tended to occur sooner in the BCAA group, but without a significant difference. 3) Although serum albumin recovered its preoperative value 9 mo after surgery in the control group, only 6 mo was required for recovery in the BCAA group. Total protein showed similar changes, but neither group showed any difference in changes of aspartate aminotransferase, alanine transferase, or platelets. 4) One year postoperatively, the change from the preoperative indocyanine green retention rate at 15 min after intravenous administration tended to be worse in the control group, but not significantly so. 5) In the BCAA group, hyaluronic acid and type IV collagen 7S improved significantly sooner than in the control group. Conclusions BCAA supplementation after hepatectomy promotes rapid improvement in protein metabolism and inhibits progression to liver cirrhosis. Administration of BCAA after hepatectomy is considered beneficial to a patient’s nutritional state.

Postoperative infections after hepatectomy sometimes lead to fatal hepatic failure, but the mechanism of the hepatic failure is unclear. Wistar rats underwent 90% hepatectomy, and were then divided into three groups: (i) the SAL group, injected with normal saline; (ii) the LPS group, injected with lipopolysaccharide (LPS) every day for 1 week; and (iii) the LPS plus TGF-Ab (LPS+TGF-Ab) group, injected with LPS with anti-transforming growth factor-β1 (TGF-β1) antibody. We investigated survival rates, TGF-β1 expression in the liver, liver regeneration by proliferating cell nuclear antigen labeling index, hepatocyte apoptosis by single stranded DNA labeling index, and perisinusoidal fibrosis using Masson's trichrome staining. The LPS group (30.4%) had a significantly lower survival rate than the SAL group (84%) and tended to be lower than the LPS+TGF-Ab group (49.4%). Liver regeneration in the LPS group was significantly lower than in the other groups. In the LPS group, hepatocyte apoptosis and perisinusoidal fibrosis was significantly more remarkable, and TGF-β1 expression was significantly higher than in the SAL group. TGF-β1 enhanced by LPS plays an important role in the mechanism of hepatic failure by infections after hepatectomy, especially in inhibition of liver regeneration, and induction of hepatocyte apoptosis and perisinusoidal fibrosis.