[A Case of Stage â £ Gastric Cancer with Multiple Liver Metastases, Resected Primary Tumor after Chemotherapy, and Alive for 3.5 Years without Recurrence].

A 67-year-old man visited our hospital for epigastric pain. Esophagogastroduodenoscopy(EGD)revealed type 2 gastric cancer from the cardia to the gastric angle, and histopathological examination revealed papillary adenocarcinoma(pap), HER2-positive. Contrast-enhanced CT showed wall thickening mainly in the posterior wall of the gastric body, enlarged lymph nodes that were lumped together with the main lesion, and 8 low-absorption areas with ring shaped contrast effects in both lobes of the liver. The patient was diagnosed as gastric cancer cT4aN(+)M1[HEP], clinical Stage ⅣB. Six courses of capecitabine plus cisplatin plus trastuzumab(XP plus Tmab)therapy and 17 courses of capecitabine plus trastuzumab(X plus Tmab)therapy were performed. After chemotherapy, liver and lymph node metastases disappeared on CT and MRI. EGD showed residual gastric cancer, and the policy was to resect the primary tumor. Laparoscopic total gastrectomy with D2 lymph node dissection was performed. Pathological results showed T1b(SM)depth, no lymph node metastasis, and histologic response was Grade 2a. Six courses of X plus Tmab were administered as postoperative adjuvant chemotherapy, but were discontinued at the patient's request. Currently, 5 years have passed since the first chemotherapy and 3.5 years have passed since the surgery, and the patient is alive without recurrence, suggesting that the conversion surgery may have contributed to the prolonged survival.

Efficacy of bailout surgery for preventing intraoperative biliary injury in acute cholecystitis.

BACKGROUND: Bailout surgery (BOS; partial cholecystectomy, open conversion, and fundus-first approach) has been recommended for difficult cases to ensure safe performance of cholecystectomy. However, the efficacy of BOS for preventing intraoperative massive bleeding and bile duct injury (BDI) remains unclear, especially in the context of acute cholecystitis (AC). This study aimed to retrospectively validate the feasibility of BOS for AC. METHODS: We enrolled 479 patients who underwent emergency cholecystectomies for AC between 2011 and 2021. Univariate and multivariate analyses were performed to detect the risk factors for BOS in patients with AC. Perioperative variables were compared between patients who underwent total cholecystectomy (TC) and those who underwent BOS. Propensity score matching analysis was performed to compare the two groups. RESULTS: Significant differences in American Society of Anesthesiologists physical status and Charlson Comorbidity Index scores, TG18 severity grading, white blood cell count, and albumin and C-reactive protein (CRP) levels were found between the TC and BOS groups. Preoperative CT imaging demonstrated severe inflammation evidenced by gallbladder wall thickness, enhancement of the liver bed, and duodenal edema in the BOS group compared to the TC group. Postoperative complications were significantly higher in the BOS group than in the TC group. Further, BDI was completely prevented by BOS. Multivariate analysis identified TG18 grade ≥ II, CRP ≥ 7.7, and duodenal edema as independent risk factors for BOS. After PSM analysis, postoperative complications were not worse in patients who underwent BOS rather than TC. Among BOS procedures, laparoscopic BOS (lap-BOS) was the most efficacious in preventing intraoperative blood loss and postoperative bile leakage. CONCLUSION: Severity grading > II, elevated CRP levels, or duodenum edema revealed by CT were determined to be risk factors impeding total cholecystectomy. BOS is a safe, feasible, and efficacious procedure for preventing BDI. Among BOS procedures, lap-BOS showed better postoperative outcomes.

[A Case of Postoperative Peritoneal Dissemination Recurrence of CY1 Gastric Cancer with cCR after Nab-PTX Therapy].

A 72-year-old man visited his local doctor for gastric discomfort. Esophagogastroduodenoscopy revealed a type 3 tumor on the gastric antrum, and histopathological examination revealed a moderately differentiated adenocarcinoma(tub2). The patient was referred to our hospital and CT scan revealed wall thickening with contrast effect in the gastric angle but no enlarged lymph nodes in the region. The patient was diagnosed as cT3N0M0, Stage ⅡB gastric cancer and underwent open distal gastrectomy and D2 lymph node dissection. No peritoneal dissemination was observed, but intraoperative laparoscopic cytology showed Class Ⅴ. The patient was diagnosed as CY1 Stage Ⅳ gastric cancer, and treated with S-1 plus Tmab therapy starting 1 month after surgery. One year postoperative follow-up CT revealed recurrence of peritoneal disseminations, and the patient was treated with nab-PTX as a second-line therapy. Tumor shrinkage was achieved steadily, and the peritoneal disseminations disappeared at the CT after 12 courses, resulting in cCR. Thereafter, cCR continued and treatment was terminated at the 17th course. Seven years have passed since the end of chemotherapy, and the patient is still alive without recurrence.

[A Case of Postoperative Recurrence of Liver Metastasis after Gastrectomy for Gastric Cancer-No Recurrence for Five Years after Twice Liver Resections].

The patient was an 89-year-old man. He underwent laparoscopic distal gastrectomy for gastric cancer and was diagnosed as T1bN1M0, Stage ⅠB. Eight months after surgery, a CT scan showed an 18 mm-sized hypodense mass in S6 of the liver, and the patient was diagnosed with recurrent liver metastasis. He was treated with 3 courses of CapeOX therapy, and the response was judged as partial response(PR). Laparoscopic partial hepatic S6 resection was performed for the single liver metastasis. The pathological results showed liver metastasis of gastric cancer. Capecitabine was started as adjuvant chemotherapy. Nine months after surgery for liver metastasis, CT scan showed a 12 mm-sized single tumor in S5 and the patient was diagnosed with recurrent liver metastasis. The patient underwent laparoscopic partial hepatectomy after 3 courses of weekly paclitaxel plus ramucirumab therapy. The pathological result showed liver metastasis of gastric cancer. After the surgery, adjuvant chemotherapy was not administered according to the patient's request. Seven years have passed since the resection of the gastric cancer, and 5 years have passed since the resection of the second liver metastasis, and the patient has not had any recurrence.

Efficacy of upfront hepatectomy without neoadjuvant chemotherapy for resectable colorectal liver metastasis.

BACKGROUND: Hepatectomy for resectable colorectal liver metastasis (CRLM) is recommended. However, the efficacy of upfront hepatectomy without neoadjuvant chemotherapy (NAC) is unclear due to the uncertainty of perioperative systemic chemotherapy. Moreover, it is crucial to predict the prognosis when considering perioperative chemotherapy. This study evaluated the impact of neoadjuvant chemotherapy on the prognosis of patients with resectable CRLM and assessed the usefulness of Beppu's nomogram for predicting prognosis. METHODS: This retrospective study identified 88 consecutive inpatients who underwent primary hepatic resection for CRLM; 58 received neoadjuvant chemotherapy and 30 underwent upfront surgery. Factors associated with recurrence-free survival were identified via univariate and multivariate analysis. Furthermore, propensity score analysis using inverse probability of treatment weighting (IPTW) was performed. RESULTS: On univariate analysis, poor recurrence-free survival was associated with multiple tumors, advanced primary tumor stage, vascular invasion by the primary tumor, a Beppu's nomogram score ≥ 6, and neoadjuvant chemotherapy. On multivariate analysis, a Beppu's nomogram score ≥ 6 and neoadjuvant chemotherapy were independent risk factors for recurrence. Neoadjuvant chemotherapy recipients had a higher incidence of lymph node metastasis and vascular invasion than non-recipients. Propensity score analysis revealed no significant difference in the recurrence-free survival rate between these groups. CONCLUSIONS: Our results show that upfront hepatectomy without neoadjuvant chemotherapy can be considered for resectable CRLM treatment. Beppu's nomogram score can be a tool for predicting the prognosis of patients with CRLM.

A novel model for predicting posthepatectomy liver failure based on liver function and degree of liver resection in patients with hepatocellular carcinoma.

BACKGROUND: The permissible liver resection rate for preventing posthepatectomy liver failure (PHLF) remains unclear. We aimed to develop a novel PHLF-predicting model and to strategize hepatectomy for hepatocellular carcinoma (HCC). METHODS: This retrospective study included 335 HCC patients who underwent anatomical hepatectomy at eight institutions between 2013 and 2017. Risk factors, including volume-associated liver-estimating parameters, for PHLF grade B-C were analyzed in a training set (n = 122) via multivariate analysis, and a PHLF prediction model was developed. The utility of the model was evaluated in a validation set (n = 213). RESULTS: Our model was based on the three independent risk factors for PHLF identified in the training set: volume-associated indocyanine green retention rate at 15 min, platelet count, and prothrombin time index (the VIPP score). The areas under the receiver operating characteristic curve of the VIPP scores for severe PHLF in the training and validation sets were 0.864 and 0.794, respectively. In both sets, the VIPP score stratified patients at risk for severe PHLF, with a score of 3 (specificity, 0.92) indicating higher risk. CONCLUSION: Our model facilitates the selection of the appropriate hepatectomy procedure by providing permissible liver resection rates based on VIPP scores.

Laparoscopic versus open limited liver resection for hepatocellular carcinoma with liver cirrhosis: a propensity score matching study with the Hiroshima Surgical study group of Clinical Oncology (HiSCO).

BACKGROUND: Laparoscopic liver resection (LLR) has evolved as a safe and effective alternative to conventional open liver resection (OLR) for malignant lesions. However, LLR in cirrhotic patients remains challenging. This study analyzed the perioperative and oncological outcomes of LLR for hepatocellular carcinoma (HCC) with cirrhosis compared with OLR using propensity score matching. METHODS: A multicenter retrospective analysis of records of patients who underwent limited liver resection for HCC and were histologically diagnosed with liver cirrhosis between January 2009 and December 2017 in the eight institutions belonging to the Hiroshima Surgical study group of Clinical Oncology was performed. The patients were divided into two groups: the LLR and OLR groups. After propensity score matching, we compared clinicopathological features and outcomes. RESULTS: In total 256 patients with histological liver cirrhosis who underwent limited liver resection for HCC were included in this study; 58 patients had undergone LLR, and the remaining 198 patients OLR. The number of tumors was higher, tumor size was larger, and difficulty score was significantly higher in the OLR group before propensity matching. After the matching, the data of the well-matched 58 patients in each group were evaluated; the intraoperative blood loss was lower in the LLR group (p = 0.004), and incidence of the postoperative complications was significantly higher in the OLR group (p = 0.019). The duration of the postoperative hospital stay was significantly shorter in the LLR group (p < 0.001). There were no differences between two groups in overall survival and recurrent-free survival. CONCLUSIONS: LLR decreased the incidences of postoperative complications, shortened the duration of postoperative hospital stay. Thus, LLR is a safe and feasible procedure even in patients with cirrhosis.

A Multicenter, Randomized, Controlled Trial Comparing Reinforced Staplers with Bare Staplers During Distal Pancreatectomy (HiSCO-07 Trial).

BACKGROUND: Although distal pancreatectomy (DP) using a reinforced stapler is expected to reduce PF, no multicenter RCT has been performed. To investigate whether reinforced staplers reduce the incidence of clinically relevant pancreatic fistula (PF) after DP compared with staplers without reinforcement. METHODS: Between July 2016 and December 2017, patients scheduled for DP were enrolled in a multicenter, randomized, controlled trial (RCT) at nine hospitals in Hiroshima Japan. Patients were randomized either to reinforced stapler or bare stapler. The primary endpoint was incidence of clinically relevant PF. This RCT was registered with UMIN Clinical Trial Registry (UMIN000022341). RESULTS: A total of 122 patients were assigned to reinforced stapler (n = 61) or bare stapler (n = 61), and 119 patients (61 reinforced stapler and 59 bare stapler) were analyzed. There was no significant difference in the incidence of clinically relevant PF between the reinforced stapler and bare stapler groups (16.3% vs. 27.1%, p = 0.15). Furthermore, the rates of major complication (16.3% vs. 18.6%, p = 0.74), postpancreatectomy hemorrhage (0% vs. 3.4%, p = 0.08), and median postoperative in-hospital days (19 days vs. 20 days, p = 0.78) did not differ between the two groups. Within a subset of 82 patients in whom the thickness of pancreatic transection line was less than 14 mm, a significant difference was found in the incidence of clinically relevant PF (4.5% vs. 21.0% in the reinforced stapler vs. bare stapler groups, respectively, p = 0.01). CONCLUSIONS: Reinforced stapler for pancreatic transection during DP does not reduce the incidence of clinically relevant PF compared to stapler without reinforcement.

Long-term donor quality of life after living donor liver transplantation in Japan.

AIMS: This study examined the long-term quality of life (QOL) of living liver donors (LLDs) in Japan using both generic and LLD-specific instruments. METHODS: The sample comprised 374 LLDs from five university hospitals in Japan who underwent surgery more than a year previously. QOL was evaluated using the Short Form-36 health survey (SF-36) and LLD-QOL scale. RESULTS: SF-36 results indicated that the overall long-term QOL of LLDs was significantly better than the Japanese standard. When comparing by donor factors, LLDs whose recipients were children scored higher for "satisfaction" than those whose recipients were adults on the LLD-QOL scale. LLDs with complications had lower QOL for "scars" and "burden" on the LLD-QOL scale but no differences in SF-36 scores. LLDs with longer hospital stay had lower physical QOL on SF-36 and lower QOL for "scars" and "after-effects" on the LLD-QOL scale. LLDs whose recipients have died showed lower mental QOL on SF-36 and lower "satisfaction" and greater "lack of understanding of donor health" on the LLD-QOL scale. CONCLUSIONS: Our multicenter study clarified the long-term QOL of LLDs and suggested that donors' QOL was related to the donors' and recipients' ages, donor's complications and hospital stay length, and recipient's prognosis.

Identifying the needs for teaching fundamental knowledge of laparoscopic surgery: a cross-sectional study in Japan.

BACKGROUND: Recently, laparoscopic surgery (LS) has become a more common procedure than traditional open surgery. Although LS-related adverse events have been reported, there is no formal, standardized curriculum to teach the fundamentals of LS in Japan. Understanding surgeons' knowledge regarding LS is crucial for developing an educational curriculum. The purpose of this study was to determine the baseline knowledge on LS of surgeons and surgical trainees in Japan. METHODS: Participants completed 24 multiple-choice questions testing basic cognitive knowledge of LS and a questionnaire regarding the status of laparoscopic education. The examination was developed according to the 13 content domains of the Fundamentals of Laparoscopic Surgery (FLS) program. Scores were compared between post-graduate year (PGY) > 5 and PGY 1-5 participants. Data are expressed as median scores and interquartile ranges. Wilcoxon signed-rank test was used for statistical analysis. RESULTS: A total of 195 surgeons and surgical trainees from 10 teaching hospitals (PGY1-5: 66, PGY > 5: 129) across Japan completed the examination. The median score in the entire cohort was 75 [67; 83] %, with significantly higher scores in the PGY > 5 group compared to the PGY1-5 group (79 [75; 83] % vs. 67 [58; 75] %, p < 0.001). The differences in performance were due to better scores for PGY > 5 group on the sections "equipment," "patient considerations," "abdominal access," "tissue handling," "hemorrhage and hemostasis," "tissue approximation," and "exiting the abdomen." Overall, the median scores in the "energy sources" and "establishment and physiology of the pneumoperitoneum" subsections were lower than in other domains. All participants agreed on the need for fundamental knowledge and a formal educational curriculum. CONCLUSIONS: Compared to experienced surgeons, surgical trainees had lesser knowledge about performing LS. Regardless of the years of experience, there are crucial knowledge gaps in specific areas regarding safe LS that should be addressed by implementing an educational curriculum.

Surgeons have knowledge gaps in the safe use of energy devices: a multicenter cross-sectional study.

BACKGROUND: Despite the widespread use of surgical energy devices and the potential for rare but serious complications, pilot data from North America suggest that surgeons and surgical trainees have knowledge gaps in their safe use. The purpose of this study was to determine baseline knowledge of general surgeons and surgical trainees regarding the safe use of electrosurgery (ES) across varying levels of experience in Japan. METHODS: Participants completed a 35-item multiple-choice question examination, testing critical knowledge of ES. The examination was developed according to the objectives and blueprints of SAGES' Fundamental Use of Surgical Energy™ curriculum. Sections of the examination included: "principles of ES," "ES-related adverse events," "monopolar and bipolar devices," and "pediatric considerations and interference with implantable devices." Scores were compared between PGY > 5 and PGY 1-5 participants. RESULTS: A total of 145 general surgeons and surgical trainees of all years after medical school (PGY 1-5: 57, PGY > 5: 88) from ten academic and five community hospitals completed the assessment (mean age 35; 91% male). The mean score in the entire cohort was 58 ± 12% (range 23-83%), with significantly higher scores in the PGY > 5 group compared to the PGY 1-5 group (60 ± 11 vs. 53 ± 12%, p < 0.01). Among all participants, 92% were not familiar with best practices when using ES on patients with a pacemaker; 44% believe that ES uses thermal energy from cautery; 19% did not know how to manage an operating room fire; 16% thought that a dispersive electrode should be cut to fit a child; and 27% believe that insulation failure in minimally invasive surgical instruments is mostly visible under careful inspection. CONCLUSIONS: General surgeons and trainees at all levels have knowledge gaps in the safe and effective use of energy devices, regardless of years of experience. There is a need for educational curricula to help address these gaps and contribute to safer surgery.

[A Case of Resected Giant Gastrointestinal Stromal Tumor Associated with Intraperitoneal Bleeding Following Imatinib Administration].

A 76-year-old woman with tarry stool was referred to our hospital for further examination. Contrast-enhanced computed tomography(CT)revealed a heterogeneous 15 cm tumor located in the left upper abdominal cavity. The tumor had a rich vascularity and was associated with intra-abdominal bleeding. Gastroscopy showed a large submucosal tumor in the gastric body. A biopsy was performed, and the patient was diagnosed with a c-kit-positive gastrointestinal stromal tumor(GIST)of the stomach. Imatinib mesylate(400mg/day)was administered for 6 months. Vascularity in the tumor was diminished and no new lesion had emerged, although there was no remarkable reduction in tumor size. The patient underwent partial gastrectomy and splenectomy with curative intent. She is currently alive 1 year and 4 months after surgery with no evidence of recurrence.

Intrahepatic triglyceride measurement and estimation of viability in rat fatty livers by near-infrared spectroscopy.

AIM: This study investigated the features of fatty livers using near-infrared (NIR) spectroscopy and validated the usefulness of NIR spectroscopy for the measurement of intrahepatic triglyceride (TG) contents and evaluation of viability in fatty livers. METHODS: In vitro, we examined specific spectra for each purified TG fraction by NIR. In vivo, the differences between the spectra obtained from normal and fatty livers before warm ischemia and the differences between the spectra obtained from each rat liver before and after warm ischemia were subjected to multicomponent analysis. RESULTS: In vitro experiments revealed a specific peak at 925 nm in major TG fractions, and NIR spectroscopy precisely detected changes in TG volume. In vivo experiments revealed that NIR spectroscopy detected TG content changes in rat fatty livers induced by a choline-deficient diet following the addition of purified TG spectrum for NIR spectroscopic analysis in least square curve fitting. The TG level in the fatty livers measured by NIR spectroscopy significantly correlated with the morphometric measurement of lipid content in the livers. NIR spectroscopy also revealed decreased levels of total hemoglobin (Hb) and oxidized Hb and maintenance of homeostasis in cytochrome redox states in fatty livers under normal condition. However, NIR spectroscopy showed irreversible deterioration of hepatic microcirculation, Hb oxygenation and homeostasis of the cytochrome redox states in fatty livers after 60-min warm ischemia reperfusion. CONCLUSION: These studies demonstrated that NIR spectroscopy can quantitatively measure the intrahepatic TG content in addition to simultaneously evaluating microcirculation and Hb oxygenation.

Hepatic Sclerosed Hemangioma: a case report and review of the literature.

BACKGROUND: Although cavernous hemangioma is one of the most frequently encountered benign hepatic neoplasms, hepatic sclerosed hemangioma is very rare. We report a case of hepatic sclerosed hemangioma that was difficult to distinguish from an intrahepatic cholangiocarcinoma by imaging studies. CASE PRESENTATION: A 76-year-old male patient with right hypochondralgia was referred to our hospital. Abdominal ultrasonography revealed a heterogeneously hyperechoic tumor that was 59 mm in diameter in segment 7 of the liver. Dynamic computed tomography showed a low-density tumor with delayed ring enhancement. Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI) demonstrated a low-signal intensity mass with ring enhancement on T1-weighted images. The mass had several high-signal intensity lesions on T2-weighted images. EOB-MRI revealed a hypointense nodule on the hepatobiliary phase. From these imaging studies, the tumor was diagnosed as intrahepatic cholangiocarcinoma, and we performed laparoscopy-assisted posterior sectionectomy of the liver with lymph node dissection in the hepatoduodenal ligament. Histopathological examination revealed a hepatic sclerosed hemangioma with hyalinized tissue and collagen fibers. CONCLUSION: Hepatic sclerosed hemangioma is difficult to diagnose preoperatively because of its various imaging findings. We report a case of hepatic sclerosed hemangioma and review the literatures, especially those concerning imaging findings.

Synchronous double cancers of primary hepatic adenosquamous carcinoma and hepatocellular carcinoma: report of a case.

A 76-year-old male was referred for the treatment of liver tumors detected by abdominal computed tomography (CT). Dynamic CT revealed a low-density tumor with an irregularly enhanced rim in the left lateral sector, and a highly enhanced, well-circumscribed tumor in the caudate lobe, accompanied by dilation of the intrahepatic biliary ducts in the left lobe. Preoperative imaging studies led to the diagnosis of double cancers consisting of intrahepatic cholangiocarcinoma and hepatocellular carcinoma (HCC). Left hemihepatectomy with caudate lobectomy was performed. The postoperative course was uneventful. Microscopic evaluation revealed that the tumor in the left lateral sector was adenosquamous carcinoma (ASC), whereas that in the caudate lobe was HCC. This report presents the first case describing the resection of synchronous double cancers of primary hepatic ASC and HCC.

Reliability and validity of a new living liver donor quality of life scale.

PURPOSE: To develop a living liver donor (LLD) quality of life (QOL) scale and test its reliability and validity. METHODS: We sent a draft questionnaire comprising 38 questions to 965 LLDs from five hospitals. To evaluate test-retest reliability, the questionnaire was re-sent 2 weeks later to some of the donors from one hospital. RESULTS: Of the 447 (54.5 %) donors who responded, 15 were excluded. Factor analysis of 26 items extracted 7 subscales; namely, damage from the operation, scarring, satisfaction, burden, after-effects, digestive symptoms, and lack of understanding of donor health. We analyzed construct validity on the basis of factor analysis and observed significant correlations among the seven subscales. Criterion-related validity was confirmed by significant correlation with the 36-item Short-Form Health Survey scores. None of the subscales showed unreasonable values. We evaluated the subscale reliability for internal consistency (α = 0.670-0.868, except for "digestive symptoms", α = 0.431) and test-retest reliability (r = 0.749-0.918). The factor "digestive symptoms" needs careful consideration because of low internal consistency. CONCLUSION: The findings of this study confirmed the reliability and validity of the LLD QOL scale, which can be used for quantitatively evaluating the QOL of LLDs.

Curative surgery for primary squamous cell carcinoma of the liver: a rare case study.

Primary squamous cell carcinoma (SCC) of the liver is an extremely rare disease with a very poor prognosis. An 83-year-old woman was referred to our hospital with left abdominal pain. Laboratory data showed mildly elevated C-reactive protein and biliary enzymes. The tumor markers carcinoembryonic antigen, alpha-fetoprotein, and carbohydrate antigen 19-9 were within normal ranges. Contrast-enhanced computed tomography revealed a 60 mm-sized low-density mass with poor contrast enhancement located in the lateral segment of the liver. The tumor showed low signal on T1-weighted magnetic resonance imaging (MRI) and high signal on T2-weighted MRI. The cytology of bile juice showed no malignant findings. Endoscopic ultrasound-guided fine-needle aspiration biopsy was performed, which was suggestive of primary hepatic SCC. Tumor markers cytokeratin 19 fragment (CYFRA) and SCC-related antigen were elevated, at 25.2 ng/mL and 14.7 ng/mL, respectively. Left lobectomy and hilar lymph node dissection were performed. One month after surgery, the tumor marker values showed a marked decrease of 1.8 ng/mL for CYFRA and 0.3 ng/dL for SCC-related antigen. The patient has been without recurrence for more than one and half year postoperatively. SCC-related antigen and CYFRA were markedly decreased after tumor resection in this case, which may suggest their utility as tumor markers for SCC of liver origin.

Rho inhibitor prevents ischemia-reperfusion injury in rat steatotic liver.

BACKGROUND & AIMS: Hepatic stellate cells are thought to play a role in modulating intrahepatic vascular resistance based on their capacity to contract via Rho signaling. We investigated the effect of a Rho-kinase inhibitor on ischemia-reperfusion injury in the steatotic liver. METHODS: Steatotic livers, induced by a choline-deficient diet in rats, were subjected to ischemia-reperfusion injury. Hepatic stellate cells isolated from steatotic livers were analyzed for contractility and Rho signaling activity. The portal pressure of the perfused rat liver and the survival rate after ischemia-reperfusion were also investigated. RESULTS: Hepatic stellate cells from steatotic livers showed increased contractility and upregulation of Rho-kinase 2 compared with those from normal livers. Furthermore, endothelin-1 significantly enhanced the contractility and phosphorylation level of myosin light chain and cofilin in hepatic stellate cells isolated from steatotic livers. A specific Rho-kinase inhibitor, fasudil, significantly suppressed the contractility and decreased the phosphorylation levels of myosin light chain and cofilin. Serum levels of endothelin-1 were markedly increased after IR in rats with steatotic livers, whereas fasudil significantly decreased endothelin-1 serum levels. Rats with steatotic livers showed a significant increase in portal perfusion pressure after ischemia-reperfusion and a significant decrease in survival rate; fasudil treatment significantly reduced these effects. CONCLUSIONS: Activation of Rho/Rho-kinase signaling in hepatic stellate cells isolated from steatotic livers is associated with an increased susceptibility to ischemia-reperfusion injury. A Rho-kinase inhibitor attenuated the activation of hepatic stellate cells isolated from steatotic livers and improved ischemia-reperfusion injury in steatotic rats.

Prognostic significance of antithrombin III levels for outcomes in patients with hepatocellular carcinoma after curative hepatectomy.

BACKGROUND: Although several studies have shown that serum antithrombin III (ATIII) has anti-inflammatory effects, the prognostic value of ATIII in HCC is unknown. We investigated the influence of preoperative ATIII levels on the outcome of patients who underwent hepatectomy for hepatocellular carcinoma (HCC). METHODS: Data from 440 patients (314 patients with ATIII ≥ 70 % and 126 patients with ATIII <70 %) who underwent curative hepatectomy for HCC were retrospectively collected and analyzed. To overcome bias due to the different distribution of covariates for the 2 groups, propensity score matching was performed on the patients, and outcomes were compared. RESULTS: The propensity score analysis revealed that 65 patients with ATIII of ≥ 70 % (group 1) and 65 patients with ATIII of <70 % (group 2) had the same preoperative and operative characteristics (excluding the ATIII level). The overall survival rate and the disease-free survival rate was significantly higher in group 1 than in group 2 (P = 0.005 and 0.011, respectively). Multivariate analysis showed that ATIII was a significant favorable factor for overall survival and disease-free survival of patients with HCC after curative hepatectomy. CONCLUSIONS: The prognosis of patients with HCC was found to be associated with preoperative antithrombin III levels. ATIII may be useful for predicting outcomes of patients with HCC after curative hepatectomy.

Impact of pegylated interferon therapy on outcomes of patients with hepatitis C virus-related hepatocellular carcinoma after curative hepatic resection.

BACKGROUND: Several published reports investigating the effects of interferon (IFN) therapy on survival and tumor recurrence after curative resection of hepatocellular carcinoma (HCC) have been inconclusive. The aim of this study is to investigate the efficacy of pegylated-IFN (peg-IFN) therapy after curative hepatic resection for HCC in patients infected with hepatitis C virus (HCV). METHODS: Data from 175 patients who underwent curative hepatic resection for HCC associated with HCV were retrospectively collected and analyzed; 75 patients received peg-IFN therapy after surgery, whereas 100 patients did not receive IFN therapy. To overcome biases resulting from the different distribution of covariates in the two groups, a one-to-one match was created using propensity score analysis. After matching, patient outcomes were analyzed. RESULTS: After one-to-one matching, patients (n = 38) who received peg-IFN therapy after surgery and patients (n = 38) who did not receive IFN therapy had the same preoperative and operative characteristics. The 3- and 5-year overall survival rates of patients who received peg-IFN therapy after hepatic resection were significantly higher than those of patients who did not receive IFN therapy (P = 0.00135). The 3- and 5-year overall survival rates were 100 and 91.7% and 76.6 and 50.6% in the peg-IFN group and non-IFN group, respectively. There was no significant difference in disease-free survival between the two matched groups (P = 0.886). CONCLUSION: Peg-IFN therapy may be effective as an adjuvant chemopreventive agent after hepatic resection in patients with HCV-related HCC.