Prognostic grade for resecting hepatocellular carcinoma: multicentre retrospective study.

BACKGROUND: Surgical treatment for hepatocellular carcinoma (HCC) is advancing, but a robust prediction model for survival after resection is not available. The aim of this study was to propose a prognostic grading system for resection of HCC. METHODS: This was a retrospective, multicentre study of patients who underwent first resection of HCC with curative intent between 2000 and 2007. Patients were divided randomly by a cross-validation method into training and validation sets. Prognostic factors were identified using a Cox proportional hazards model. The predictive model was built by decision-tree analysis to define the resection grades, and subsequently validated. RESULTS: A total of 16 931 patients from 795 hospitals were included. In the training set (8465 patients), four surgical grades were classified based on prognosis: grade A1 (1236 patients, 14.6 per cent; single tumour 3 cm or smaller and anatomical R0 resection); grade A2 (3614, 42.7 per cent; single tumour larger than 3 cm, or non-anatomical R0 resection); grade B (2277, 26.9 per cent; multiple tumours, or vascular invasion, and R0 resection); and grade C (1338, 15.8 per cent; multiple tumours with vascular invasion and R0 resection, or R1 resection). Five-year survival rates were 73.9 per cent (hazard ratio (HR) 1.00), 64.7 per cent (HR 1.51, 95 per cent c.i. 1.29 to 1.78), 50.6 per cent (HR 2.53, 2.15 to 2.98), and 34.8 per cent (HR 4.60, 3.90 to 5.42) for grades A1, A2, B, and C respectively. In the validation set (8466 patients), the grades had equivalent reproducibility for both overall and recurrence-free survival (all P < 0.001). CONCLUSION: This grade is used to predict prognosis of patients undergoing resection of HCC.

Randomized clinical trial comparing two vessel-sealing devices with crush clamping during liver transection.

BACKGROUND: Previous RCTs have failed to demonstrate the usefulness of combining energy devices with the conventional clamp crushing method to reduce blood loss during liver transection. Here, the combination of an ultrasonically activated device (UAD) and a bipolar vessel-sealing device (BVSD) with crush clamping was investigated. METHODS: Patients scheduled to undergo hepatectomy at the University of Tokyo Hospital or Nihon University Itabashi Hospital were eligible for this parallel-group, single-blinded randomized study. Patients were assigned to a control group (no energy device used), an UAD group or a BVSD group. The primary endpoint was the volume of blood loss during liver transection. Outcomes of the control group and the combined energy device groups (UAD plus BVSD) were first compared. Pairwise comparisons among the three groups were made for outcomes for which the combined energy device group was superior to the control group. RESULTS: A total of 380 patients were enrolled between July 2012 and May 2014; 116 patients in the control group, 122 in the UAD group and 123 in the BVSD group were included in the final analysis. Median blood loss during liver transection was lower in the combined energy device group (245 patients) than in the control group (116 patients): median 190 (range 0-3575) versus 230 (range 3-1570) ml (P = 0·048). Pairwise comparison revealed that blood loss was lower in the BVSD group than in the control group (P = 0·043). CONCLUSION: The use of energy devices combined with crush clamping reduced blood loss during liver transection. Registration number: C000008372 (www.umin.ac.jp/ctr/index.htm).

Potential responders to FOLFOX therapy for colorectal cancer by Random Forests analysis.

BACKGROUND: Molecular characterisation using gene-expression profiling will undoubtedly improve the prediction of treatment responses, and ultimately, the clinical outcome of cancer patients. METHODS: To establish the procedures to identify responders to FOLFOX therapy, 83 colorectal cancer (CRC) patients including 42 responders and 41 non-responders were divided into training (54 patients) and test (29 patients) sets. Using Random Forests (RF) algorithm in the training set, predictor genes for FOLFOX therapy were identified, which were applied to test samples and sensitivity, specificity, and out-of-bag classification accuracy were calculated. RESULTS: In the training set, 22 of 27 responders (81.4% sensitivity) and 23 of 27 non-responders (85.1% specificity) were correctly classified. To improve the prediction model, we removed the outliers determined by RF, and the model could correctly classify 21 of 23 responders (91.3%) and 22 of 23 non-responders (95.6%) in the training set, and 80.0% sensitivity and 92.8% specificity, with an accuracy of 69.2% in 29 independent test samples. CONCLUSION: Random Forests on gene-expression data for CRC patients was effectively able to stratify responders to FOLFOX therapy with high accuracy, and use of pharmacogenomics in anticancer therapy is the first step in planning personalised therapy.

Criteria for drain removal following liver resection.

BACKGROUND: Abdominal drains have been placed prophylactically and removed in liver resection without robust evidence. The present study was designed to establish the optimal time for removal of such drains. METHODS: Data on abdominal prophylactic drains were analysed in a consecutive series of patients who underwent liver resection for malignancy between 2006 and 2009. Bilirubin levels in drain fluid were measured and bacteriological cultures were taken on days 1, 3, 5 and 7 after surgery. Drains were removed on day 3 if the drain-fluid bilirubin level was less than 5 mg/dl and bacteriological cultures were negative. Drains remained in situ until these conditions were met. RESULTS: A total of 514 abdominal drains were placed in 316 patients operated on in the study period. Fifty-eight patients (18·4 per cent) had positive drain-fluid cultures and 14 (4·4 per cent) had bile leakage (drain-fluid bilirubin level 5 mg/dl or more). Only one patient required ultrasound-guided abdominal drainage. On multivariable analysis, drain-fluid bilirubin level on day 3 after surgery was the strongest predictor of infection (odds ratio 15·11, 95 per cent confidence interval 3·04 to 92·11; P < 0·001). The area under the receiver operating characteristic curve on day 3 had the highest predictive value: 83·6 per cent accuracy and 3·9 per cent false-positive rate for a drain-fluid bilirubin level of 3·01 mg/dl (51·5 µmol/l). CONCLUSION: The '3 × 3 rule' (drain-fluid bilirubin level below 3 mg/dl on day 3 after operation) is an accurate criterion for removal of prophylactically placed abdominal drains in liver resection.

Molecular karyotyping of human hepatocellular carcinoma using single-nucleotide polymorphism arrays.

Genomic amplification of oncogenes and inactivation of suppressor genes are critical in the pathogenesis of human cancer. To identify chromosomal alterations associated with hepatocarcinogenesis, we performed allelic gene dosage analysis on 36 hepatocellular carcinomas (HCCs). Data from high-density single-nucleotide polymorphism arrays were analysed using the Genome Imbalance Map (GIM) algorithm, which simultaneously detects DNA copy number alterations and loss of heterozygosity (LOH) events. Genome Imbalance Map analysis identified allelic imbalance regions, including uniparental disomy, and predicted the coexistence of a heterozygous population of cancer cells. We observed that gains of 1q, 5p, 5q, 6p, 7q, 8q, 17q and 20q, and LOH of 1p, 4q, 6q, 8p, 10q, 13q, 16p, 16q and 17p were significantly associated with HCC. On 6q24-25, which contains imprinting gene clusters, we observed reduced levels of PLAGL1 expression owing to loss of the unmethylated allele. Finally, we integrated the copy number data with gene expression intensity, and found that genome dosage is correlated with alteration in gene expression. These observations indicated that high-resolution GIM analysis can accurately determine the localizations of genomic regions with allelic imbalance, and when integrated with epigenetic information, a mechanistic basis for inactivation of a tumor suppressor gene in HCC was elucidated.

Modulation of the immune response to transplanted tumors in rats by selective depletion of neutrophils in vivo using a monoclonal antibody: abrogation of specific transplantation resistance to chemical carcinogen-induced syngeneic tumors by selective depletion of neutrophils in vivo.

The role of neutrophils in transplantation immunity to syngeneic rat tumors was examined using a monoclonal antibody (RP-3) that depletes rat neutrophils selectively in vivo. We used 2 chemical carcinogen-induced transplanted tumors of different antigenic specificity (KMT-17 and KDH-8 of WKA rat origin). When neutrophils were selectively depleted by i.p. injection of RP-3 at the time of in vivo priming with X-irradiated tumor cells, the growth of subsequently s.c. transplanted identical tumors was not inhibited, in contrast to the group of rats immunized without RP-3 treatment. Tumor growth was also not inhibited when the immune rats were treated with RP-3 at the time of identical viable tumor cell challenge. These results suggest that neutrophils play a role in both the priming and effector phases of specific transplantation resistance to syngeneic tumors.

Production of factor(s) that render polymorphonuclear leukocytes cytostatic from spleen cells stimulated with a streptococcal preparation, OK-432.

We previously reported the augmentation of tumor cytotoxicity of polymorphonuclear leukocytes (PMN) by in vivo administration of a streptococcal preparation, OK-432 (S. Watabe et al., J. Natl. Cancer Inst., 72: 1365-1370, 1984). The present study was undertaken to elucidate the mechanisms of the phenomena. Mouse and rat spleen cells were stimulated in vitro with OK-432. The culture supernatants from the stimulated spleen cells (OK sup) contained factor(s) that rendered mouse and rat PMN cytostatic [neutrophil activating factor (NAF)]. The stimulation of spleen cells with a small dose of OK-432 (0.05 micrograms/ml) resulted in the production of maximum NAF, and NAF was produced soon (12 h) after OK-432 stimulation. NAF was partially inactivated with 60 degrees C 30-min treatment, and completely inactivated with 100 degrees C 10 min. NAF was sensitive to pH 2 treatment. The treatment of PMN with OK sup for 5 min at 37 degrees C was sufficient to induce cytostatic activity of PMN. That OK sup contained gamma-interferon and recombinant gamma-interferon showed NAF activity indicate that gamma-interferon is a NAF in OK sup.

A comparative study of postoperative complications after hepatectomy in patients with and without chronic liver disease.

BACKGROUND: Although hepatic resection is the most reliable treatment for hepatocellular carcinoma, impaired liver function because of cirrhosis or chronic hepatitis contributes to relatively high rates of postoperative complications. We have reviewed a series of hepatectomies at our institution and investigated risk factors for complications after hepatectomy in patients with impaired liver compared with patients with normal liver. METHODS: From October 1994 to March 1998, 277 hepatectomies for hepatocellular carcinoma, cholangiocellular carcinoma, metastatic liver tumors, and other hepatic diseases were performed. In an attempt to clarify the safety of hepatectomy for the impaired liver at our institution, we did a comparative study of postoperative complications after hepatectomy in 2 groups: patients with impaired livers (187 hepatectomies) and patients with normal livers (90 hepatectomies). RESULTS: Of the 277 hepatectomies, bile leakage occurred in 25 patients (16 in impaired livers vs 9 in normal livers), abdominal infection in 45 patients (30 vs 15 patients), wound infection in 13 patients (9 vs 4 patients), pleural effusion in 52 patients (35 vs 17 patients), atelectasis in 26 patients (17 vs 9 patients), pneumonia in 4 patients (3 vs 1 patients), ileus in 6 patients (3 vs 3 patients), intra-abdominal hemorrhage in 3 patients (0 vs 3 patients), and hyperbilirubinemia in 5 patients (4 vs 1 patients). Hepatic insufficiency and hospital death were not experienced in this series. The mean postoperative hospital stay was 22.9 days (23.5 vs 23.1 days), and except for intra-abdominal hemorrhage there was no statistically significant difference between the 2 groups. CONCLUSIONS: Hepatectomy for the impaired liver is now as safe a procedure as for the normal liver, provided the overall guidelines outlined in our algorithm are followed.

Reconstruction of the hepatic and portal veins using a patch graft from the right ovarian vein.

We describe a patch-graft technique using the right ovarian vein for reconstruction of the right hepatic and portal veins after resection in hepatectomy and pancreatoduodenectomy in female patients. After partial resection of the right hepatic vein or portal vein for removing either hepatic or pancreatic tumors, the defects were covered by a patch graft from the right ovarian vein. The proximal part of the vein, 5 cm in length, was harvested, divided longitudinally, and then divided into two equal parts, which were sutured together to give a patch measuring 2.5 x 2.0 cm. This technique can be applied for reconstruction after partial resection of the hepatic or portal vein in hepatectomy and pancreatoduodenectomy.

Hepatocellular carcinoma followed by Waldenström's macroglobulinemia: a case report.

A case of hepatocellular carcinoma associated with Waldenström's macroglobulinemia is reported. During treatment and follow-up of hepatocellular carcinoma, a 54-year-old man was found to have a progressive monoclonal increase in serum IgM level and subsequently was diagnosed as having Waldenström's macroglobulinemia. Chemotherapy was carried out to prevent hyperviscosity syndrome due to Waldenström's macroglobulinemia without any surgical management for hepatocellular carcinoma. The association of these diseases is quite rare; only 6 cases have been reported in the literature, and this is the first case in which hepatocellular carcinoma preceded Waldenström's macroglobulinemia.

Mass-forming inflammatory periductal fibrosis mimicking hilar bile duct carcinoma.

A case of a rare benign biliary lesion at the hepatic hilum mimicking hilar bile duct carcinoma is reported. A 73-year-old man was found to have gastric cancer by gastrointestinal fiberscopy. Dilated right intrahepatic bile ducts and a 2-cm mass in the right hepatic duct were demonstrated by further imaging investigations. He was finally diagnosed as having hilar bile duct and gastric carcinomas, and underwent right portal vein embolization followed by a single-stage extended right hepatectomy and total gastrectomy. Pathologically, however, the lesion in the right hepatic duct showed inflammatory changes with periductal fibrosis, without any signs of malignancy. A literature search revealed 11 such cases including the present one.

Endometriosis of the rectum causing bowel obstruction: a case report.

A 42-year-old pre-menopausal woman complaining of lower abdominal pain was referred to our hospital. A barium enema showed rectal stenosis and colonoscopy revealed that the mucosa at the stenotic site was normal with no cancerous changes. Pelvic computed tomography demonstrated an adhesion between the rectum and uterus and a thickened rectal wall. The patient underwent exploratory laparotomy under a diagnosis of rectal stenosis. The rectum was found to be surrounded by inflammatory fibrous tissue, which caused the stenosis. As no dissection plane was discernible between the rectum and uterus, low anterior resection of the rectum and hysterectomy were performed. Histological examination showed that endometrial-type glands extended circumferentially around the rectum and invaded the rectal submucosal layer and subsequently, endometriosis of the rectum was diagnosed.

Presacral epidermal cyst: a report of an adult case.

A 46-year-old woman was found to have a giant cyst behind the uterus during preoperative examinations of an uterine myoma. Pelvic and digital examinations revealed an oval, palpable mass behind the uterus with no mucosal lesions on the rectal wall. Ultrasonography and computed tomography showed an uterine myoma with a cystic change and an oval mass behind the uterus, which compressed the rectum to the left side. The patient underwent hysterectomy and tumor resection via laparotomy. The tumor was found to be located in the presacral space. Histological examination showed a cyst lined by keratinized squamous epithelium with no cutaneous adnexal structures and subsequently, the tumor was diagnosed as an epidermal cyst.

Hepatic resection for hepatocellular carcinoma -- Japanese experience.

In the past 20 years, thanks to the early detection of hepatocellular carcinomas (HCCs), good perioperative care, the evaluation of functional liver reserve, preoperative portal embolization and the improvement in surgical techniques such as intraoperative ultrasonography, the surgical resection of HCC has become very safe. We have performed 367 hepatectomies on 352 patients since 1990 with a surgical mortality, hospital mortality, blood transfusion rate and 5-year survival rate of 0.27, 0.82, and less than 10 and 47.4%, respectively. Our standard method for selecting surgical procedures and perioperative care resulting in low blood transfusion rates and almost no mortality are described. Since 1990, ethanol injection for HCC ablation has been extensively used in Europe and Japan, but results are poorer than with surgical intervention. Therefore, in patients with small HCCs and good liver function, the first choice treatment should not be ethanol injection, but surgical resection.

Inflammatory pseudotumors of the liver: prevalence and clinical impact in surgical patients.

BACKGROUND/AIMS: Progress in diagnostic imaging has increased the number of focal liver lesions detected and reports of an occasional finding of inflammatory pseudotumors of the liver are becoming numerous. To estimate their prevalence and clinical impact in surgical series we evaluate retrospectively our experience. METHODOLOGY: Four hundred and three patients carriers of a total of 717 focal liver lesions underwent liver resection consecutively in our Department from October 1995 to August 1999. All these patients underwent surgery. RESULTS: After surgical resection, 3 patients each proved to be carrying an IPT nodule accounting for 0.7% of all patients and 0.4% of all focal liver lesions. One inflammatory pseudotumor was only disclosed intraoperatively in a patient with an hepatocellular carcinoma. The other 2 accounted for 20% of the patients whose preoperative diagnoses were wrong. The operative procedures for the inflammatory pseudotumor nodules were: wedge resection, because the inflammatory pseudotumor was considered a new malignancy, a limited resection and a left extended hepatectomy with bilioenteric anastomosis, distal gastrectomy and lymphoadenectomy in one patient each. Inflammatory pseudotumors accounted for 33% of wrong indication for surgery. CONCLUSIONS: Our experience shows that, despite the low prevalence of hepatic inflammatory pseudotumors, their impact in the appropriate management of patients with focal liver lesions is not irrelevant.

A study of biohazard protection for farming modules of lunar base CELSS.

For the Closed Ecological Life Support System (CELSS) of a manned lunar base which is planned to be built on the moon early in the 21st century, several proposed programs exist to grow vegetables inside a farming module. At the 40th IAF (Malaga, 1989) the author et al presented a proposal for supplying food and nutrients to a crew of eight members, a basic concept which is based on growing four kinds of vegetables. This paper describes measures for biohazard protection in farming modules. In this study, biohazard protection means prevention of the dispersion of plant diseases to other plant species or other portions of farming beds.

The seasonal variation in the microbial agents implicated in the etiology of diarrheal diseases among children in Lao People's Democratic Republic.

During 1994-1995, the etiological structure of children's diarrhea was monitored in outpatients at Mahosot Hospital, Vientiane, Lao PDR. Of the 191 children studied, 42% had stool specimens positive for enteropathogens; 22% had rotavirus, 21.5% enteropathogenic E. coli, 4.7% Shigella flexneri, 2.9% Campylobacter jejuni, 2.1% Shigella sonnei, and 0.5% each of Giardia intestinalis and Entamoeba histolytica. No Vibrio cholerae and Salmonella spp. was detected in this monitoring. In children under five years, rotaviruses were detected almost all round the year with a maximum prevalence in January in the dry season. Shigella species were highly detected in June to July in the rainy season.

Bacterial diarrhea in Laos, a region where cholera was endemic.

There were cholera outbreaks in Lao PDR since 1993. Two provinces were epidemic areas of cholera in 1993. However the area of cholera occurrence increased to 7 provinces through 1994. Then a bacterial survey had done for the purpose of public health improvement. EPEC was markedly isolated from the hospital in Vientiane. In apparent infection of Salmonella and non-01 Vibrio cholerae with soldiers stationed in the island in Mekong River belong to Vientiane were pointed out. The outbreak of diarrhea in suburban village of Vientiane, the diarrhea was not due to cholera but due to Shigella dysenteriae and Aeromonas sobria. As far as results in the capital city Vientiane and the Vientiane province go, it could say that there was no record and isolation of V. cholerae or non-01 V. cholerae 0139 in this study. On the contrary, Vibrio cholerae 01 serotype Eltor Ogawa was isolated although the community declared the end of the cholera outbreak. This study pointed out the importance of establishing sanitary conditions and health education systems in Lao PDR.

Characterization of Aeromonas hydrophila: a comparative study of strains isolated from diarrheal feces and the environment.

Thirty-five strains of Aeromonas hydrophila isolated from feces of diarrheal patients and from the environments were collected from Thailand and Japan. The physiological, biochemical, and serological characteristics, antibiotic resistance patterns and cell surface-related properties were compared. The diarrheal and environmental isolates of A hydrophila were found to be remarkably consistent in general culture and biochemical characteristics, with the exception of the reaction to D-arabinose in which the diarrheal strains were positive and environmental strains were negative. The plasmid patterns and cell surface-related properties of the environmental and diarrheal isolates were different. All strains produced Vero cell cytotoxin, hemolysin and lecithinase at 37 degrees, 30 degrees and 15 degrees C. In contrast, 83% of the environmental strains produced these virulence factors even at 4 degrees C. All strains indicated almost uniform susceptibility to the 16 antibiotics tested. Variations were found in the plasmid profile, toxin production in relation to the differences of temperature and cell surface-related properties of the strains. These variations between the clinical and environmental isolates could have potential as epidemiological markers for the sources of strains.

CELSS nutrition system utilizing snails.

At the 40th IAF Congress in Malaga, a nutrition system for a lunar base CELSS was presented. A lunar base with a total of eight crew members was envisaged. In this paper, four species of plants--rice, soybean, lettuce and strawberry--were introduced to the system. These plants were sufficient to satisfy fundamental nutritional needs of the crew members. The supply of nutrition from plants and the human nutritional requirements could almost be balanced. Our study revealed that the necessary plant cultivation area per crew member would be nearly 40 m3 in the lunar base. The sources of nutrition considered in the study were energy, sugar, fat, amino acids, inorganic salt and vitamins; however, calcium, vitamin B2, vitamin A and sodium were found to be lacking. Therefore, a subsystem to supply these elements is of considerable value. In this paper, we report on a study for breeding snails and utilizing meat as food. Nutrients supplied from snails are shown to compensate for the above mentioned lacking elements. We evaluate the snail breeder and the associated food supply system as a subsystem of closed ecological life support system.