The results of liver cryosurgery for synchronized liver metastasis from colorectal cancer

We examined our results of liver cryosurgery for synchronized liver metastasis from colorectal cancer. Twelve patients whose prognosis after the cryosurgery was clear were eligible. All of the patients received not only a resection of the colorectal primary lesion, but they also received a cryosurgery for liver metastases under the same laparotomy. These patients had been treated in this manner from 1981 to 1987. Ten of the 12 patients died from recurrent cancer. The range in survival time of 12 cases was from 6 months to 117 months, and the average survival length was 25.4 months. The examination of the results suggested that there were no cryosurgery induced anti-immunological response observed among the patients. The survival lengths of the patients with untreated cancer were good.     

Promoter hypermethylation of DAP-kinase is associated with poor survival in primary biliary tract carcinoma patients

To clarify the clinicopathological significance of promoter hypermethylation of tumor suppressor and tumor-related genes in biliary tract carcinomas, we examined the promoter methylation status of multiple genes in primary biliary tract carcinomas. These consisted of carcinomas of the bile duct, gallbladder, and duodenal ampulla. Surgical specimens were obtained from a total of 37 patients with biliary tract carcinoma. The cohort consisted of 23 patients with bile duct carcinoma, 9 patients with gallbladder carcinoma, and 5 patients with ampullary carcinoma. The methylation status of CHFR, DAP-kinase, E-cadherin, hMLH1, p16, RASSF1A, and RUNX3 was examined by methylation-specific polymerase chain reaction (MSP). The correlation between methylation status and clinicopathological characteristics was then assessed. The methylation frequencies of CHFR, DAP-kinase, E-cadherin, hMLH1, p16, RASSF1A, and RUNX3 genes were 16.2%, 21.4%, 27.0%, 8.1%, 24.3%, 27.0%, and 56.8%, respectively, in primary biliary tract carcinomas. The number of methylated genes per sample was 2.17 +/- 0.28 (average +/- SD) in bile duct carcinomas, 1.80 +/- 0.97 in ampullary carcinomas, and 0.89 +/- 0.35 in gallbladder carcinomas, with a statistically significant difference between bile duct carcinomas and gallbladder carcinomas (P = 0.02). As for clinicopathological significance, patients with a methylated RUNX3 promoter were significantly older than those with unmethylated RUNX3 (P = 0.01), and DAP-kinase methylation was more frequent in poorly differentiated tumors than in well to moderately differentiated ones (P = 0.04). The overall survival rate was significantly lower in patients with methylated DAP-kinase (P = 0.009) or RUNX3 (P = 0.034) compared to those with unmethylated genes. Furthermore, DAP-kinase methylation-positive status was independently associated with poor survival in multivariate analyses (hazard ratio = 8.71, P = 0.024). A significant proportion of primary biliary tract carcinomas exhibited promoter hypermethylation of tumor suppressor and tumor-related genes, although bile duct carcinomas are more prone to being affected by promoter methylation than are gallbladder carcinomas. Hypermethylation of DAP-kinase appears to be a significant prognostic factor in primary biliary tract carcinomas.     

Search for new biomarkers of gastric cancer through serial analysis of gene expression and its clinical implications

Gastric cancer is one of the most common human cancers and is the second most frequent cause of cancer-related death in the world. Serial analysis of gene expression (SAGE) is a powerful technique to allow genome-wide analysis of gene expression in a quantitative manner without prior knowledge of the gene sequences. SAGE on 5 samples of gastric cancer with different histology and clinical stages have created large SAGE libraries of gastric cancer that enable us to identify new cancer biomarkers. Commonly up-regulated genes in gastric cancer in comparison with normal gastric epithelia included CEACAM6, APOC1 and YF13H12. By comparing gene expression profiles of gastric cancers at early and advanced stages, several genes differentially expressed by tumor stage were also identified, including FUS, CDH17, COL1A1 and COL1A2, which should be novel genetic markers for high-grade malignancy. Regenerating gene type IV (REGIV) is one of the most up-regulated genes in a SAGE library of a scirrhous-type gastric cancer. In vitro studies using RegIV-transfected cells revealed that RegIV is secreted by cancer cells and inhibits apoptosis, suggesting that RegIV may serve as a novel biomarker and therapeutic target for gastric cancer. Production of RNA aptamers could be a useful approach to establish a detection system in blood. A custom-made array, named Ex-STOMACHIP, consisting of 395 genes, including highly differentially expressed genes identified by our SAGE and other known genes related to carcinogenesis and chemosensitivity, is useful to study the molecular pathogenesis of gastric cancer and to obtain information about biological behavior and sensitivity to therapy in the clinical setting. Combined analyses of gene expression profile, genetic polymorphism and genetic instability will aid not only cancer detection, but also characterization of individual cancers and patients, leading to personalized medicine and cancer prevention.     

The effect of taste masking agents on in situ gelling pectin formulations for oral sustained delivery of paracetamol and ambroxol

The aim of this study was to examine the influence of polyhydric alcohols (taste masking agents) on the rheological properties of in situ gelling pectin formulations and on the in vitro and in vivo release of paracetamol and ambroxol from these formulations. Gelation of orally administered pectin solutions containing calcium in complexed form occurred on release of calcium in the acidic environment of the stomach. Inclusion of 10% (w/v) sorbitol in 2% (w/v) pectin sols reduced the viscosity and ensured Newtonian flow properties. Xylitol and mannitol in similar concentrations were less effective in reducing viscosity; sucrose increased viscosity and caused non-Newtonian flow. The in vitro release of paracetamol from 2% (w/v) pectin gels formulated with 10% (w/v) of sorbitol, erythritol, xylitol or mannitol, and of ambroxol from 2% (w/v) pectin gels containing 10% (w/v) sorbitol, followed diffusion-controlled kinetics. Pectin gels (2%, w/v) containing sorbitol (10%, w/v) sustained the release of paracetamol in the rat stomach and bioavailabilities of approximately 90% of those from an orally administered paracetamol syrup were achieved. Sustained release of ambroxol from in situ gelling formulations was achieved with pectin concentrations of 1.5 and 1% (w/v) and a sorbitol concentration of 10% (w/v).     

Analysis of allelic imbalances at multiple cancer-related chromosomal loci and microsatellite instability within the same tumor using a single tumor gland from colorectal carcinomas

Genetic changes related to colorectal carcinomas are accumulated in individual tumor glands during disease progression. Microsatellite allelic analysis of individual tumor glands from 30 colorectal carcinomas using a polymerase chain reaction (PCR) assay coupled with crypt isolation was used to detect intratumoral genetic heterogeneity, the sequence of allelic imbalances (AIs) and the microsatellite instability status of single tumor glands during neoplastic progression. In addition, the CpG islands methylated phenotype (CIMP) status was examined using a methylation-specific PCR method. The specimens were divided into 2 groups: a pooled gland sample, which was composed of more than 50 tumor glands, and a single tumor gland sample. The latter consisted of 10 single tumor glands, which were obtained from the same tumor separately. Most colorectal carcinomas (27 of 30 tumors) examined were heterogeneous for at least one genetic alteration, with from 2 to 7 genotypically different subclones detected per tumor. In 12 of the 27 heterogeneous tumors, it was possible to define the order of genetic alterations during the tumor progression. By analyzing multiple single tumor glands within the same tumor, we found that various subclonal expansions were seen within the same tumors. Finally, the AI pattern of single tumor glands was not correlated with CIMP status. Most carcinomas appeared to have a heterogeneous composition. This may have resulted from the successful progression of one clone that had different AIs in many chromosomal regions. This suggests that knowledge of the different genotypes of multiple single tumor glands may help clarify the process of tumor progression.     

Hepatic arterial cannulation using the side holed catheter

BACKGROUND: Hepatic arterial infusion chemotherapy (HAIC) has been recognized as one of the effective treatments for patients with hepatic metastatic tumor. However it is difficult to perform HAIC in the long term without complications. This report describes the laparotomic approach using the side holed catheter, which is a novel method of implanting a catheter-port system. METHODS AND RESULTS: We designed a new anti-thrombotic catheter for HAIC. This catheter is tapered from 5F (diameter of shaft) to 3.3F (diameter at tip), and a side hole is opened 7 cm from the tip of catheter. This catheter is inserted from the gastroduodenal artery to the common hepatic artery (CHA), and the tip is put in the aorta or in the splenic artery. The side hole is adjusted distal to the CHA. In our surgical department, our new catheter was inserted in four patients at the time of their abdominal surgery. The cannulation was performed successfully in all patients. In two of them, HAIC was finished without problems at 6 months after starting, and two were still treated by HAIC at 9 and 8 months after starting. CONCLUSIONS: Initial results from a study of a new method of implanting a catheter-port system in the hepatic artery using the new tapering side hole catheter suggest that this method may enable operators to avoid complicated selective coiling and may lower the incidence of hepatic artery occlusion in patients receiving long-term HAIC.     

Examination of acute disease in the long-term geriatric ward

We investigated the acute disorder in cases at the long-term geriatric ward. Fifty seven patients were admitted to the hospital during the period of October 2002 to March 2005. In our study, the following items were analyzed: (1) the number of admission, (2) diagnosis, (3) the duration of hospital stay, and (4) the cause of death. The admission of respiratory disease patients, such as pneumonia, bronchitis and pleuritis, were most frequent and had the longest term of hospitalization. We also found that patients with respiratory disease had undergone percutaneous endoscopic gastrostomy (PEG), and their hospitalization was relatively shorter.