Neonatal outcomes of congenital diaphragmatic hernia in full term versus early term deliveries: A systematic review and meta-analysis.

This systematic review and meta-analysis aimed to review the optimal timing of delivery at term for neonates with prenatally diagnosed congenital diaphragmatic hernia (CDH). We reviewed the literature up to December 19, 2022 using MEDLINE and the Cochrane Library databases. The inclusion criteria were original articles, comparative studies of CDH neonates delivered at an early term (37-38 weeks of gestation) and at full term (39 weeks of gestation or later), and comparative studies investigating outcomes of CDH neonates. Six studies met the inclusion criteria, including 985 neonates delivered at an early term and 629 delivered at full term. The cumulative rate of survival to discharge showed no significant difference between CDH neonates delivered at an early term (395/515; 76.7%) or at full term (345/467; 73.9%) (risk ratio [RR] 1.01; 95% confidence interval [CI], 0.89-1.16; p = 0.85). Furthermore, the number of neonates requiring oxygen therapy at discharge was not significantly different between CDH neonates delivered at an early term (32/370; 8.6%) and at full term (14/154; 9.1%) (RR, 0.99; 95% CI, 0.36-2.70; p = 0.99). Therefore, the optimal timing of delivery at term for neonates with CDH remains unclear.

Prenatal predictors of mortality in fetuses with congenital diaphragmatic hernia: a systematic review and meta-analysis.

PURPOSE: This study aimed to evaluate prenatal predictors of mortality in fetuses with congenital diaphragmatic hernia (CDH). METHODS: A systematic literature search was performed to identify relevant observational studies that evaluated the ability of lung-to-head ratio (LHR), observed-to-expected LHR (o/e-LHR), observed-to-expected total fetal lung volume (o/e-TFLV), lung-to-thorax transverse area ratio (L/T ratio), intrathoracic herniation of the liver and the stomach, and side of diaphragmatic hernia, using a threshold for the prediction of mortality in fetuses with CDH. Study quality was assessed using the QUADAS-2 tool. Hierarchical summary receiver operating characteristic curves were constructed. RESULTS: A total of 50 articles were included in this meta-analysis. The QUADAS-2 tool identified a high risk of bias in more than one domain scored in all parameters. Among those parameters, the diagnostic odds ratio of mortality with o/e-LHR < 25%, o/e-TFLV < 25%, and L/T ratio < 0.08 were 11.98 [95% confidence interval (CI) 4.65-30.89], 11.14 (95% CI 5.19-23.89), and 10.28 (95% CI 3.38-31.31), respectively. The predictive values for mortality were similar between the presence of liver herniation and retrocardiac fetal stomach position. CONCLUSIONS: This systematic review suggests that o/e-LHR, o/e-TFLV, and L/T ratio are equally good predictors of neonatal mortality in fetuses with isolated CDH.

Clinical guidelines for the treatment of congenital diaphragmatic hernia.

Congenital diaphragmatic hernia (CDH) is a birth defect of the diaphragm in which abdominal organs herniate through the defect into the thoracic cavity. The main pathophysiology is respiratory distress and persistent pulmonary hypertension because of pulmonary hypoplasia caused by compression of the elevated organs. Recent progress in prenatal diagnosis and postnatal care has led to an increase in the survival rate of patients with CDH. However, some survivors experience mid- and long-term disabilities and complications requiring treatment and follow-up. In recent years, the establishment of clinical practice guidelines has been promoted in various medical fields to offer optimal medical care, with the goal of improvement of the disease' outcomes, thereby reducing medical costs, etc. Thus, to provide adequate medical care through standardization of treatment and elimination of disparities in clinical management, and to improve the survival rate and mid- and long-term prognosis of patients with CDH, we present here the clinical practice guidelines for postnatal management of CDH. These are based on the principles of evidence-based medicine using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. The recommendations are based on evidence and were determined after considering the balance among benefits and harm, patient and society preferences, and medical resources available for postnatal CDH treatment.

Impact of Anatomical Resection for Hepatocellular Carcinoma With Microportal Invasion (vp1): A Multi-institutional Study by the Kyushu Study Group of Liver Surgery.

OBJECTIVE: The aim of the present study was to evaluate the value of anatomical resection for hepatocellular carcinoma (HCC) with microportal vascular invasion (vp1) between 2000 and 2010. BACKGROUND: Vascular invasion has been reported as a prognostic factor of liver resection for HCC. Anatomical resection for HCC has resulted in optimum outcomes of eradicating intrahepatic micrometastases through the portal vein, but opposite results have also been reported. METHODS: A clinical chart review was performed for 546 patients with HCC with vp1. We retrospectively evaluated the recurrence-free survival (RFS) between anatomical (AR) and nonanatomical resection (NAR). The site of recurrence was also compared between these groups. The influence of AR on the overall survival (OS) and RFS rates was analyzed in patients selected by propensity score matching, and the prognostic factors were identified. RESULTS: A total of 546 patients were enrolled, including 422 in the AR group and 124 in the NAR group. There was no difference in the 5-year OS and RFS rates between the 2 groups. Local recurrence was significantly more frequent in the NAR group than in the AR group. In a multivariate analysis, hepatitis C virus, serum protein induced by vitamin K absence II of 380 mAU/mL or more, tumor diameter of 5 cm or more, and age of 70 years or older were significant predictors of a poor RFS after liver resection. There were no significant differences in the OS or RFS between the AR and NAR groups by a propensity score-matched analysis. CONCLUSIONS: Although local recurrence around the resection site was suppressed by AR, AR for HCC with vp1 did not influence the RFS or OS rates after hepatectomy in the modern era.

CXCL12 expression in intrahepatic cholangiocarcinoma is associated with metastasis and poor prognosis.

Intrahepatic cholangiocarcinoma is a rare malignant biliary neoplasm that causes a poor prognosis even after curative hepatectomy. Liver metastasis is the major recurrence pattern of intrahepatic cholangiocarcinoma; therefore, the prevention of liver metastasis is a desirable objective. The aim of this study is to identify gene(s) related to liver metastasis of intrahepatic cholangiocarcinoma and to examine the inhibitory effects on metastasis of intrahepatic cholangiocarcinoma by controlling such gene(s). We collected 3 pairs of intrahepatic cholangiocarcinoma frozen samples, and 36 pairs (primary and metastatic lesions) of intrahepatic cholangiocarcinoma formalin-fixed paraffin-embedded samples, from patients who underwent surgical resection at hospitals related to the Kyushu Study Group of Liver Surgery between 2002 and 2016. We carried out cDNA microarray analyses and immunohistochemistry to identify candidate genes, and evaluated one of them as a therapeutic target using human cholangiocarcinoma cell lines. We identified 4 genes related to liver metastasis using cDNA microarray, and found that CXCL12 was the only gene whose expression was significantly higher in liver metastasis than in primary intrahepatic cholangiocarcinoma by immunohistochemistry (P = .003). In prognosis, patients in the high CXCL12 group showed a significantly poor prognosis in disease-free (P < .0001) and overall survival (P = .0004). By knockdown of CXCL12, we could significantly suppress the invasive and migratory capabilities of 2 human cholangiocarcinoma cell lines. Therefore, CXCL12 might be associated with metastasis and poor prognosis in intrahepatic cholangiocarcinoma.

Prognostic Impact of Preoperative Lymph Node Enlargement in Intrahepatic Cholangiocarcinoma: A Multi-Institutional Study by the Kyushu Study Group of Liver Surgery.

BACKGROUND: Although lymph node metastasis (LNM) has been considered an important prognostic factor for intrahepatic cholangiocarcinoma (ICC), the impact of lymph node enlargement on the prognosis of ICC, and the accuracy of diagnosis of LNM, have not been fully clarified. METHODS: Using a chart review of 225 patients with ICC, we compared survival times between patients with and without lymph node enlargement, and we evaluated the accuracy of diagnosis of LNM. We also performed a multivariate analysis to determine the variables affecting overall survival in the study population. RESULTS: The survival time of patients without lymph node enlargement was significantly longer than that of patients with lymph node enlargement (median survival time [MST] 43.7 vs. 20.1 months; p = 0.007). However, in the group with enlarged lymph nodes, survival time was prolonged as a result of hepatectomy (MST 20.1 vs. 7.6 months; p < 0.01). The sensitivity of lymph node size and positron emission tomography-computed tomography findings for diagnosing LNM were 50.0 % (23/46) and 31.2 % (5/16), respectively, and were thus insufficient. Multivariate analysis identified the serum carcinoembryonic antigen (hazard ratio [HR] 1.830) and carbohydrate antigen 19-9 (HR 2.189) levels, blood transfusion (HR 1.792), intrahepatic metastasis (HR 1.988), and final stage (HR 8.684) as prognostic factors for overall survival, but lymph node enlargement was not identified as a prognostic factor. CONCLUSION: Preoperative evaluation of LNM proved to be difficult, and survival time in ICC patients with lymph node enlargement was prolonged as a result of hepatectomy. Thus, ICC patients with preoperative lymph node enlargement should not be prematurely deemed non-curative cases.

Surgical approaches for neonatal congenital diaphragmatic hernia: a systematic review and meta-analysis.

PURPOSE: The optimal surgical approach for neonatal congenital diaphragmatic hernia (CDH) remains unclear. We conducted a systematic review and meta-analysis of the effectiveness of endoscopic surgery (ES) for neonatal CDH. METHODS: A systematic literature search was conducted using MEDLINE and the Cochrane Library. Studies that compared surgical approaches for neonatal CDH were selected. Mortality and recurrence of herniation were analyzed as primary endpoints. Each study was evaluated following the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. RESULTS: Eight observational studies comparing ES and open surgery (OS) met the criteria. As compared with the OS group, the ES group showed both a significantly lower mortality rate [risk ratio (RR) 0.18, 95 % confidence interval (CI) 0.09-0.38, p < 0.0001] and a significantly higher recurrence rate (RR 3.10, 95 % CI 1.95-4.88, p < 0.00001). However, serious selection bias was seen in seven of the eight studies-because the indication of ES had been determined intentionally, the ES groups may have included less severe cases. CONCLUSION: Although the evidence was insufficient, ES was clearly associated with more recurrence than was OS. Therefore, ES should not be the routine treatment for every neonate. It is crucially important to select suitable cases for ES.

[A randomized controlled trial of postoperative adjuvant chemotherapy for colorectal cancer-optimal duration of the treatment].

METHODS: Subjects were 239 patients with colorectal cancer who underwent curative resection surgery from December 1994 to March 1997(Stage I-III b). The patients were given 5'-DFUR for postoperative 10 months as scheduled. They had been allocated into either a 1-year group or a 3-year group by dynamic randomization. 5'-DFUR was administered by an intermittent regimen such as 1,200 mg/body/day for five days followed by two days rest. All patients were followed for five years at least. RESULTS: 239 patients were enrolled in the study. Favorable prognoses in both groups were observed. Although no statistically significant differences in overall survival curves of full analysis set based on the drug administration durations, were detected(log-rank test, p=0.734), a better prognosis was found in the 3-year group(5-year OS: 92.0%; 1- year group, 91.4%; 3-year group). Adverse drug reactions resulted in low rates such as 14.8% in the 1-year group and 19.5% in the 3-year group. Grade 3 was found in either group. CONCLUSIONS: Due to a result in the present study that 5-year survival rates in both groups were far higher than anticipated, we could not finally clarify the optimal administration duration of 5'-DFUR. However, the results of the present study indicate that 5'-DFUR results in a good prognosis for colorectal cancer patients and is safe over a long / administration period.

Radiation enterocolitis requiring surgery in patients with gynecological malignancies.

PURPOSE: To identify the characteristics, risk factors, and clinical outcomes of radiation enterocolitis requiring surgery in patients with gynecologic malignancies. METHODS AND MATERIALS: The records of 1,349 patients treated with pelvic radiotherapy were retrospectively reviewed. The majority of the patients (88%) were treated with 50 Gy or 50.4 Gy pelvic irradiation in conventional fractionations with anteroposterior fields. RESULTS: Forty-eight patients (3.6%) developed radiation enterocolitis requiring surgery. Terminal ileum was the most frequent site (50%) and most of the lesions had stenosis or perforation. On univariate analysis, previous abdominopelvic surgery, diabetes mellitus (DM), smoking and primary site had an impact on the complications, and on multivariate analysis, abdominopelvic surgery, DM, and smoking were independent predictors of the complications requiring surgery. After the surgical intervention, the frequency of Grade 2 or more bleeding was significantly lower in patients treated with intestinal resection in addition to decompression than those treated with intestinal decompression alone. CONCLUSIONS: Severe radiation enterocolitis requiring surgery usually occurred at the terminal ileum and was strongly correlated with previous abdominopelvic surgery, DM, and smoking. Concerning the management, liberal resection of the affected bowel appears to be the preferable therapy.

Percutaneous ipsilateral portal vein embolization using a modified four-lumen balloon catheter with fibrin glue: initial clinical experience.

PURPOSE: The purpose of the present study was to show the feasibility and safety of ipsilateral portal vein embolization (PVE) using an improved four-lumen balloon catheter with fibrin glue. MATERIALS AND METHODS: To improve the ipsilateral PVE with fibrin glue, we modified a commercially available four-lumen balloon catheter to create a catheter comprising one lumen with a catheter tip for a guidewire, one lumen for an occlusion balloon, and two lumens, each with a side-hole just proximal to the balloon. Eight patients had hepatobiliary disease (three with bile duct carcinoma, two with gallbladder carcinoma, one with hepatocellular carcinoma, one with Caroli disease, and one with metastatic carcinoma). RESULTS: All embolization procedures were technically successful. After embolization, the volume of the future remnant liver increased a mean of 131%. There was no inadvertent embolization of portal vein branches and no major procedure-related complications. CONCLUSION: Our method is potentially easier and safer than the traditional ipsilateral method with fibrin glue using a three-lumen balloon catheter because the fourth lumen makes possible the use of a guidewire to access the targeted portal vein and measurement of any portal vein pressure elevation following PVE via the fourth lumen.

Anterior approach for right hepatectomy with hanging maneuver for hepatocellular carcinoma: a multi-institutional propensity score-matching study.

BACKGROUND: This multi-institutional study aimed to assess the benefits of anterior approach for right hepatectomy with hanging maneuver (ARH-HM) for hepatocellular carcinoma (HCC) compared with conventional right hepatectomy (CRH). METHODS: From January 2000 to December 2012, 306 patients with HCC ≥5 cm were divided into two groups: ARH-HM (n = 104) and CRH (n = 202). RESULTS: After one-to-one propensity score-matched analysis, 72 ARH-HM and 72 CRH patients presented comparable background factors. Patients in the ARH-HM group demonstrated significantly less intraoperative blood loss (480 vs. 1,242 g, P < 0.001) and a lower frequency of red cell concentrate transfusion (21.1% vs. 50.7%, P < 0.001) compared with patients in the CRH group. The 5-year overall survival rate was significantly better in the ARH-HM group compared with the CRH group (50.2% vs. 31.4%, P = 0.021). Limited to patients with HCC ≥10 cm, recurrence-free and overall survival of the ARH-HM group was significantly greater than those of the CRH group. CONCLUSION: In comparison with CRH, ARH-HM for large HCC can provide better overall survival rates with a decrease in intraoperative blood loss and transfusion rates. Survival impact was evident especially in patients with HCC ≥10 cm.

Surgical management of recurrent intrahepatic cholangiocarcinoma: predictors, adjuvant chemotherapy, and surgical therapy for recurrence: A multi-institutional study by the Kyushu Study Group of Liver Surgery.

Objectives of the present study were to identify predictors of the recurrence of intrahepatic cholangiocarcinoma (ICC), and to evaluate the survival benefit of adjuvant chemotherapy and surgical treatment for ICC recurrence. A multi-institutional retrospective study was carried out in 356 patients with ICC who underwent curative surgery at one of 14 institutions belonging to the Kyushu Study Group of Liver Surgery. A total of 214 patients (60%) had recurrence. Predictors of ICC recurrence were as follows: positive for pathological intrahepatic metastasis (im), positive for lymph node metastasis (n), positive for pathological lymphatic infiltration (ly), pathological bile duct invasion (b), and tumor size ≥4.4 cm. Adjuvant chemotherapy was given to 120 patients (34%) and, in the patients with im or tumor size ≥4.4 cm, adjuvant chemotherapy showed a survival benefit. Only 37 patients (17%) underwent surgical treatment for ICC recurrence. The surgical treatment resulted in a good 5-year survival rate (44%), which is similar to the rate obtained by the first operation for primary ICC. Prognosis of patients with primary im after the second operation was significantly worse (5-year survival 18%) compared to patients without primary im. Primary im+ should be considered a contraindication for surgical treatment for ICC recurrence.

Microsatellite instability in patients with gastric remnant cancer.

BACKGROUND: About 2% of patients who undergo partial distal gastrectomy for gastroduodenal diseases develop gastric remnant cancer 10 to 30 years after the gastrectomy. It is important in clinical practice to determine a molecular marker to identify patients susceptible to gastric remnant cancer.METHODS: We investigated nine gastric remnant cancers (from nine individuals who had gastrectomies for primary gastric cancer or gastroduodenal ulcer) for microsatellite instability (MSI) at six loci, using the polymerase chain reaction (PCR). A control group of ten patients with sporadic gastric cancers in the upper third of the stomach was also similarly analyzed.RESULTS: MSI was demonstrated in eight of nine cancers from the individuals who had had primary gastric cancer or gastroduodenal ulcer (88.9%) compared with two of ten cancers from the individuals with sporadic gastric cancer in the upper third of the stomach (20%).CONCLUSION: These results suggest that one or more MSI is associated with remnant gastric cancer after gastrectomy.

Barrett's adenocarcinoma associated with acquired eventration of the diaphragm.

We report a rare case of Barrett's adenocarcinoma asso-ciated with acquired eventration of the diaphragm in a 71-year-old woman. She initially developed dysphagia and epigastric discomfort in May, 1997. On July 9, she was referred to our Department of Surgery at the Ryukyus University Hospital for thorough examination and treatment. Esophageal adenocarcinoma and eventration of the diaphragm were revealed by exhaustive examinations, including chest X-ray, computed tomography, and magnetic resonance imaging, and proximal gastrectomy with reconstruction of jejunal interposition was performed, on August 8. Histologically, the tumor revealed that the adenocarcinoma arose from short-segment Barrett's esophagus (SSBE). It thus appears that eventration of the diaphragm may induce SSBE and Barrett's adenocarcinoma. We therefore recommend that periodic examinations of the esophagus and stomach be performed in patients with eventration of the diaphragm. Barrett's adenocarcinoma associated with acquired eventration of the diaphragm is reported. Patients with eventration of the diaphragm should undergo periodic examinations of the esophagus and stomach.

Tuberculous lymphadenopathy mimicking pancreatic neoplasm.

Abdominal tuberculosis (TB) is the sixth most common location of extrapulmonary TB involvement. Because its symptoms and signs are often nonspecific, laboratory and imaging findings mimic other diseases including carcinoma. Therefore, the diagnosis of abdominal TB is challenging. We herein report a case of 74-year-old woman who presented with abdominal pain, anorexia, and weight loss. She had been given a diagnosis of pancreatic head carcinoma. Laboratory data was unremarkable except for elevated erythrocyte sedimentation rate, CA125, and sIL-2R. CT scan revealed multiple enlarged peripancreatic lymph nodes and concentric thickening of the ileocecal wall. Colonoscopy demonstrated deformed ileocecal valve and erosions. Histological examination showed epithelioid granulomas. Laparoscopy revealed numerous white tubercles diffusely covering the parietal peritoneum. Histopathological images of peripancreatic lymph node revealed large multiple caseating granulomas surrounded by Langhans_giant cells and epithelioid cells. Polymerase chain reaction and culture of the specimens were positive for Mycobacterium tuberculosis. Tuberculous lymphadenopathy, colitis, and peritonitis were finally diagnosed. She responded well to the antitubercular treatment.

Severe late complications in patients with uterine cancer treated with postoperative radiotherapy.

AIM: Severe late complications, particularly radiation enterocolitis and leg edema, remain major problems in patients with uterine cancer, who have undergone hysterectomy and postoperative external beam radiotherapy (EBRT). We carried out this retrospective analysis to identify the incidence of risk factors for such complications. PATIENTS AND METHODS: The records of 228 patients, who underwent radical hysterectomy and postoperative EBRT (uterine cervix: 149 patients; uterine corpus: 79 patients) were reviewed retrospectively. The majority of the patients (90.8%) were treated with 50 to 50.4 Gy EBRT in conventional fractionations with anteroposterior fields. Intracavitary brachytherapy (ICBT) was administered to 9 patients (3.9%), and 35 patients (15.2%) received chemotherapy. The median follow-up for all 228 patients was 81.7 months (range, 1-273 months). RESULTS: Nineteen patients (8.3%) developed severe radiation enterocolitis with a median latency of 12.6 months, and the ileum was the most frequently affected site. On multivariate analysis, smoking was an independent predictor of severe radiation enterocolitis. Nineteen patients (8.3%) developed severe leg edema with a median latency of 32.7 months. The degree of leg edema did not improve in any of the 19 patients despite intensive treatment. On multivariate analysis, addition of ICBT was an independent predictor of severe leg edema. CONCLUSION: Severe radiation enterocolitis and severe leg edema were each observed in approximately 8% of patients with uterine cancer, who underwent postoperative radiotherapy. Severe radiation enterocolitis correlated strongly with smoking, and severe leg edema correlated strongly with addition of ICBT. These factors should be considered before administering postoperative radiotherapy to uterine cancer patients.

Malignant epithelioid angiomyolipoma in the kidney and liver of a patient with pulmonary lymphangioleiomyomatosis: lack of response to sirolimus.

A 26-year-old woman with lymphangioleiomyomatosis (LAM) was hospitalized for the surgical excision of a giant abdominal tumor of right kidney origin. The pathological diagnosis of the tumor was conventional angiomyolipoma (AML). After 8 months, 2 liver tumors appeared and grew rapidly. The tumors were resected, and the pathological finding of these tumors was epithelioid AML. Thereafter, metastatic multiple lung tumors appeared, and there was local recurrence of the liver tumors. Sirolimus, an mTOR protein inhibitor, was used to treat epithelioid AML. However, the drug did not inhibit the rapid growth of the tumor at all. This finding suggests that sirolimus might not be effective against epithelioid AML, and in such cases, complete surgical resection should be the treatment of choice.

Expression of anti-apoptotic protein, Bcl-2, in liver regeneration after a partial hepatectomy.

BACKGROUND: Although Bcl-2 is well known to have anti-apoptotic activities in vitro and in vivo, the role of Bcl-2 relating to liver regeneration remains controversial. The aim of this study was to document the effect of Bcl-2 expression on liver regeneration in rats undergoing a partial hepatectomy. MATERIAL AND METHODS: Adult male Wistar rats (n = 4/group) at 72 h before undergoing a 70% partial hepatectomy (PH) were administered 1 x 10(9) plaque-forming units of adenovirus vector encoding either human Bcl-2 (group 1) or LacZ (group 2) intravenously and were sacrificed at 0, 12 h, and at 1, 2, 3, 7, 14, and 21 days postoperatively. In group 3, normal saline was injected instead of adenovirus vector. Liver regeneration was monitored by measuring the restituted liver mass and proliferating cell nuclear antigen (PCNA) immunostaining. The incidence of apoptosis in the liver was analyzed by the immunohistochemical detection of single-stranded DNA at 14 and 21 days postoperatively. RESULTS: The restituted liver mass showed significantly higher values in group 1 (26.1 +/- 7.2%) than in group 2 (14.7 +/- 6.8%) and 3 (13.6 +/- 5.0%) at 1 day after PH (P < 0.05). The PCNA labeling index was significantly higher in group 1 (47.2 +/- 9.9%) than in groups 2 (19.0 +/- 7.8%) and 3 (19.2 +/- 15.2%) at 1 day after a partial hepatectomy (P < 0.05). The hepatocyte growth factor (HGF) mRNA expression was significantly lower in group 1 than in group 2 at 12 h after PH (P < 0.05). The number of single-stranded DNA-positive cells decreased significantly more in group 1 (5.67 +/- 1.53 positive cells/10 fields per tissue) than those in group 2 (18.33 +/- 7.57 positive cells/10 fields per tissue) at 14 days after PH. CONCLUSIONS: These results thus indicated that an overexpression of anti-apoptotic protein Bcl-2 does not necessarily have an anti-apoptotic effect on liver regeneration but appears to have a pro-proliferative effect in the early phase of liver regeneration.

Up-regulation of hepatocyte growth factor caused by an over-expression of transforming growth factor beta, in the rat model of fulminant hepatic failure.

BACKGROUND: The role of transforming growth factor beta (TGF-beta), a potent regulator of cellular growth, was investigated in the rat model of fulminant hepatic failure (FHF). MATERIALS AND METHODS: The rat FHF model was created by a combination of a 68% partial hepatectomy (PH) and 7% of necrosis (each n = 25 in Groups 1, 2 and 3). Adenovirus mediated gene transfer of mature human TGF-beta1 gene was performed by the systemic injection of AxCAhTGFb1 (1 x 10(9) pfu) in Group 1, 3 days before FHF. In control Groups 2 and 3, recombinant lacZ adenovirus (AxCAlacZ, Group 2) and normal saline (1 ml, Group 3) were used, instead of AxCAhTGFb1. RESULTS: An excessive expression of TGF-beta1 in Group 1 resulted in an inhibition of hepatocyte proliferation (24-48 h after FHF) and gaining of liver weight (24-48 h), increased expression of HGF in liver tissue (24 h), and decreased expression of TGF-alpha (24 h), compared to those in control Groups 2 and 3. Serum IL-6 levels were also elevated by a TGF-beta1 over-expression at 24 hrs after FHF in Group 1. CONCLUSIONS: The forced expression of TGF-beta1 in the FHF liver yields both a secondary increase of HGF production and a suppression of liver regeneration, which might explain the mechanism of increased serum HGF observed in a clinical FHF. TGF-beta1 is thus thought to have an important role in inhibiting liver regeneration after FHF.