[A case of peritoneal serous papillary adenocarcinoma].

A78-year-old female was admitted to our hospital with anorexia due to ascites. We were not able to diagnose by cytological diagnosis. For a definite diagnosis she underwent an open biopsy. Histological findings revealed observable papillary adenocarcinoma with psammoma body, carcinoma cells were positive for Ber-EP4 on immunostaining, and ovaries were normal. Thus, we made a diagnosis of peritoneal serous papillary adenocarcinoma. She was treated by intraperitoneal administration of CDDP(20 mg/day: day 1, every four weeks). Ascites vanished and CA125 was within the normal range. There was no recurrence after 3 years, but Virchow's lymph node metastasis occurred. The patient is still alive 12 months after metastasis with CDDP intraperitoneal administration.

[A case of advanced gastric cancer successfully treated by surgery after chemotherapy with S-1/CDDP].

A-46-year-old male with advanced-stage IV multicentric gastric cancer was treated with S-1/CDDP as neoadjuvant chemotherapy. S-1 (initially 100 mg/day, up to 120 mg/day) was orally administered for 3 weeks (day 1-21) followed by 1 drug-free week as a course, and CDDP (initially 60 mg/day, up to 100 mg/day) was administered by intravenous drip on day 8. After the fourth course, a significant tumor reduction was obtained and curative surgery was performed. Thereafter, S-1 therapy was continued. There has not been any recurrence for 19 months postoperatively.

Perioperative blood transfusion and survival following curative hepatic resection for hepatocellular carcinoma.

BACKGROUND/AIMS: The association between transfusion and recurrence after resection for hepatocellular carcinoma (HCC) is still under debate. The influences of perioperative blood transfusion on survival and recurrence after curative hepatic resection for HCC and prognostic factors in patients with blood transfusion were evaluated. METHODOLOGY: Curative hepatectomy was performed in 210 patients (57%) with and 158 (43%) without perioperative blood transfusion. Prognostic factors were evaluated by univariate and multivariate analysis using Cox's proportional hazards model. RESULTS: Multivariate analysis revealed that perioperative blood transfusion was an independent predictor for recurrence in patients with serum low albumin level (< 3.5 g/dL). In transfused group, stage IV, large tumor size (> or = 5 cm), high value of ICGR15 (> or = 20%), and old age (> or = 60 year) were independent factors of poor disease-free survival. CONCLUSIONS: Perioperative blood transfusion promotes the recurrence of HCC after hepatic resection in patients with hypo-albuminemia. In transfused patients, establishment of strategy for recurrence based on pTNM staging, tumor size, ICGR15, and age may be required to improve survival.

Pancreatic polypeptide administration reduces insulin requirements of artificial pancreas in pancreatectomized dogs.

An artificial endocrine pancreas is a mechanical device that frequently measures blood glucose and adjusts the rate of insulin infusion to maintain normoglycemia. In this study, we evaluated the effect of pancreatic polypeptide (PP) on insulin requirements after total pancreatectomy. However, other endocrine hormones are needed not only to facilitate the effect of insulin, but also to regulate insulin functions in vivo. In this study, the effect of PP infusion on insulin requirements after total pancreatectomy in dogs is examined. After total pancreatectomy, five dogs were supported by artificial endocrine pancreas model STG-22 for 72 h. In a second group of five dogs, both insulin and PP were infused. Mean blood glucose levels and insulin requirements were compared between the two groups. There was no difference in mean plasma glucose levels between the two groups. In all 10 dogs, the mean blood glucose level for 72 h was 110 +/- 4 mg/dL and was tightly controlled between 65 and 190 mg/dL. However, the insulin requirement for the first and second postoperative days in the group treated with PP was significantly less than that of the control group (90.0 +/- 20.8 mU/kg vs. 445.0 +/- 151.9 mU/kg; P < 0.05, and 562.7 +/- 126.5 mU/kg vs. 1007.7 +/- 144.9 mU/kg; P < 0.05, respectively). We conclude that infusion of PP reduces the insulin requirement for the initial 48 h in pancreatectomized dogs treated with an artificial endocrine pancreas.

Specific gene expression and therapy for pancreatic cancer using the cytosine deaminase gene directed by the rat insulin promoter.

Suicide gene therapy has been shown to be an effective means of destroying pancreatic cancer cells, but cell-specific delivery of the gene is required to limit host toxicity. The objective of this study is to determine whether the rat insulin promoter (RIP) will permit cell-specific gene delivery and subsequent cell death in human pancreatic cancer cells. The RIP DNA was amplified using polymerase chain reaction (PCR), and the purified fragment was inserted into pCR-Blunt II-TOPO plasmid at the SpeI site, which contains the coding sequence of yeast cytosine deaminase (CD). Transfection assays were carried out using both RIP-lacZ and RIP-CD DNA constructs in two human pancreatic cancer cell lines, PANC-1 and MIA PaCa-2. Reporter assays using X-gal staining were performed, and the in vitro cytotoxicity was examined in RIP-CD-transfected cells treated with 5-flucytosine for 5 days. The expression levels of CD protein in the transfected cells were determined 2 days after transfection by Western blot analysis. The expression levels of insulin promoter factor (IPF-1/PDX-1) in these human pancreatic cell lines, as well as in freshly isolated human pancreatic cancer specimens, were determined using in situ immunohistochemistry analysis. After transfection with RIP-lacZ, only PANC-1 cells, but not MIA PaCa-2 cells, were positive for RIP-lacZ expression, indicating that RIP-directed reporter gene expression occurred only in PANC-1 cells. After transfection with RIP-CD and treatment with 5-flucytosine, PANC-1 cells had a significantly increased cell death rate compared with that of MIA PaCa-2 cells, suggesting that RIP-directed suicide gene expression occurred only in PANC-1 cells. Western blot analysis demonstrated that only PANC-1 cells were able to express the CD protein and that significantly increased levels of PDX-1 were found in PANC-1 but not in Mia PaCa-2 cells. In situ immunohistochemical analysis of both cell lines showed that PDX-1 was only expressed in the nuclei of PANC-1 cells and not in MIA PaCa-2 cells. Furthermore, two freshly isolated human pancreatic cancer specimens had significantly increased levels of PDX-1. The RIP is activated in PANC-1 cells, but not in Mia PaCa-2 cells, and the mechanism of activation is via PDX-1. Pancreatic cancer-specific cytotoxicity can be achieved with the use of RIP-CD and 5-flucytosine treatment in vitro. Significantly increased levels of PDX-1 have been found in human pancreatic cancer specimens. These results suggest that RIP could be used for cell-specific suicide gene therapy to target human pancreatic tumors.

Current progress in suicide gene therapy for cancer.

Standard chemotherapeutic agents and ionizing radiation destroy dividing cells. Because tumor cells divide more rapidly than normal cells, there is a therapeutic index in which damage to the cancer cells is maximized while keeping the toxicity to the normal host cells acceptable. Suicide gene therapy strives to deliver genes to the cancer cells, which convert nontoxic prodrugs into active chemotherapeutic agents. With this strategy, the systemically administered prodrug is converted to the active chemotherapeutic agent only in cancer cells, thereby allowing a maximal therapeutic effect while limiting systemic toxicity. A literature search was conducted using the MEDLINE database from 1990 to 2001 to identify articles related to suicide gene therapy for cancer. A number of suicide gene systems have been identified, including the herpes simplex virus thymidine kinase gene, the cytosine deaminase gene, the varicella-zoster virus thymidine kinase gene, the nitroreductase gene, the Escherichia coli gpt gene, and the E. coli Deo gene. Various vectors, including liposomes, retroviruses, and adenoviruses, have been used to transfer these suicide genes to tumor cells. These strategies have been effective in cell culture experiments, laboratory animals, and some early clinical trials. Advances in tissue- and cell-specific delivery of suicide genes using specific promoters will improve the clinical utility of suicide gene therapy.

Quantification of cardiac stress during EGD without sedation.

BACKGROUND: Although the complication rate of endoscopy is low, EGD may induce cardiac stress. The aim of this study was to quantify cardiac stress during EGD. METHODS: Heart rate, blood pressure, cardiac output, and peripheral oxygen saturation were measured during endoscopy without sedation in 7 volunteers. Cardiac output was measured with an automated echocardiographic technique. Cardiac index, left ventricular work index, and rate-pressure product were calculated. Serum catecholamine concentrations were measured before and after the examination. RESULTS: Heart rate increased significantly when the endoscope was located in the esophagus compared with the rate before insertion (p < 0.05). No significant changes in cardiac index and left ventricular work index were observed during endoscopy. Rate-pressure product increased significantly at the point of esophageal observation compared with that before insertion (p < 0.05). The rate-pressure product was maximally increased during esophageal observation at 66% over baseline (95% CI [45%, 86%]). Serum concentration of norepinephrine rose significantly after the examination (p < 0.05). CONCLUSIONS: Cardiac output did not increase during EGD without sedation in healthy male volunteers. Cardiac stress increased during EGD as indicated by a 66% increase in rate-pressure product. The cardiac stress was approximately equal to that observed in 3.3 to 5 metabolic equivalents of treadmill exercises.

Cloned cytosine deaminase gene expression of Bifidobacterium longum and application to enzyme/pro-drug therapy of hypoxic solid tumors.

Bifidobacterium longum is a nonpathogenic anaerobic bacterium among normal bacterial flora. Recently, it was reported that B. longum accumulated in hypoxic solid tumors. The gene of interest was expressed in transfected B. longum by the shuttle vector pBLES100 in solid tumors. In this report, we constructed pBLES100-S-eCD, which included the cytosine deaminase gene. We confirmed by western blotting that transfected B. longum produced cytosine deaminase. In addition, transfected B. longum produced cytosine deaminase that converted 5-fluorocytosine into 5-fluorouracil. B. longum could be useful for enzyme/pro-drug therapy of hypoxic solid tumors.