Proton pump inhibitor after endoscopic resection for esophageal squamous cell cancer: multicenter prospective randomized controlled trial.

BACKGROUND: Whether proton pump inhibitors (PPIs) relieve heartburn or precordial pain after endoscopic resection (ER) for esophageal squamous cell carcinoma (ESCC) remains unclear. The aim of this study was to investigate the efficacy of PPI therapy for these symptoms after ER for ESCC. METHODS: We conducted a multicenter prospective randomized controlled trial among 15 hospitals in Japan. In total, 229 patients with cT1a ESCC were randomly assigned to receive PPI therapy for 5 weeks after ER (the PPI group, n = 115) or follow-up without PPI therapy (the non-PPI group, n = 114). The primary end point was the incidence of gastroesophageal reflux disease (GERD)-like symptoms after ER from a self-reported questionnaire (Frequency Scale for Symptoms of GERD). Secondary end points were ulcer healing rate at 5 weeks, incidence of pain, improvement rate of symptoms in those who started PPI therapy because of GERD-like symptoms in the non-PPI group, and adverse events. RESULTS: No significant difference was observed in the incidence of GERD-like symptoms after ER between the non-PPI and PPI groups (30 % vs 34 %, respectively). No significant differences were observed in the ulcer healing rate at 5 weeks (84 % vs 85 %) and incidence of pain within 1 week (36 % vs 45 %). In nine of ten patients (90 %) who started PPI therapy because of GERD-like symptoms in the non-PPI group, PPI administration relieved GERD-like symptoms. No adverse events related to PPI administration were observed. CONCLUSION: PPI therapy is not efficacious in reducing symptoms and did not promote healing of ulcers in patients undergoing ER for ESCC.

High expression of N-acetylglucosaminyltransferase IVa promotes invasion of choriocarcinoma.

BACKGROUND: Gestational trophoblastic diseases (GTDs) are related to trophoblasts, and human chorionic gonadotropin (hCG) is secreted by GTDs as well as normal placentas. However, the asparagine-linked sugar chains on hCG contain abnormal biantennary structures in invasive mole and choriocarcinoma, but not normal pregnancy or hydatidiform mole. N-acetylglucosaminyltransferase-IV (GnT-IV) catalyses ß1,4-N-acetylglucosamine branching on asparagine-linked oligosaccharides, which are consistent with the abnormal sugar chain structures on hCG. METHODS: We investigated GnT-IVa expression in GTDs and placentas by immunohistochemistry, western blot, and RT-PCR. We assessed the effects of GnT-IVa knockdown in choriocarcinoma cells in vitro and in vivo. RESULTS: The GnT-IVa was highly expressed in trophoblasts of invasive mole and choriocarcinoma, and moderately in extravillous trophoblasts during the first trimester, but not in hydatidiform mole or other normal trophoblasts. The GnT-IVa knockdown in choriocarcinoma cells significantly reduced migration and invasive capacities, and suppressed cellular adhesion to extracellular matrix proteins. The extent of ß1,4-N-acetylglucosamine branching on ß1 integrin was greatly reduced by GnT-IVa knockdown, although the expression of ß1 integrin was not changed. In vivo studies further demonstrated that GnT-IVa knockdown suppressed tumour engraftment and growth. CONCLUSION: These findings suggest that GnT-IVa is involved in regulating invasion of choriocarcinoma through modifications of the oligosaccharide chains of ß1 integrin.

Long-term outcomes of endoscopic submucosal dissection for colorectal epithelial neoplasms.

BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) provides a high en bloc resection rate with less invasiveness than surgical resection for large or scarring gastrointestinal neoplasms. However, detailed outcomes in colorectal ESD are still lacking. The aim of our study was to elucidate short- and long-term outcomes of colorectal ESD. PATIENTS AND METHODS: 310 consecutive colorectal epithelial neoplasms (146 adenomas, 164 carcinomas), in 290 patients, which fulfilled our indication criteria and were treated with ESD between July 2000 and December 2008 were studied. ESD was done by three skilled endoscopists. As short-term outcomes, rates of en bloc resection, en bloc plus R0 resection, and major complications were analyzed. As long-term outcomes, disease-free and overall survival were assessed in 224 patients. RESULTS: Rates of en bloc resection and en bloc plus R0 resection were 90.3 % and 74.5 %, respectively. Eight patients underwent additional colectomy due to histopathologically proven possible node-positive cancer. Intraoperative perforations occurred with 14 lesions (4.5 %), which were treated successfully only by endoscopic clipping. Emergent surgery was needed for one case of postoperative perforation. Blood transfusion due to intraoperative massive bleeding was required in 1 case (0.3 %). Postoperative bleeding occurred with four lesions (1.3 %), and was endoscopically managed without blood transfusion. Local recurrence was detected in 4 lesions (4/202 patients, 2.0 %); resection had been piecemeal in all 4. During a median follow-up of 38.7 months (range 12.8 - 104.2), the 3- and 5-year overall/disease-specific survivals were 97.1/100 % and 95.3/100 %, respectively. CONCLUSIONS: Colorectal ESD showed favorable long-term outcomes. It may largely replace colectomy for node-negative colorectal epithelial neoplasia.

Predictors of postoperative stricture after esophageal endoscopic submucosal dissection for superficial squamous cell neoplasms.

BACKGROUND AND STUDY AIMS: Although endoscopic submucosal dissection (ESD) is becoming accepted as an established treatment for superficial esophageal squamous cell neoplasms, the risks for developing postoperative stricture have not been elucidated. PATIENTS AND METHODS: This was a retrospective study at a single institution. From January 2002 to October 2008, 65 patients with high-grade intraepithelial neoplasms (HGINs) or m2 carcinomas treated by ESD were enrolled. Predictors of postoperative stricture were investigated by comparing results from 11 patients who developed strictures with those from 54 patients who did not. RESULTS: Significant differences between the two groups were observed in longitudinal diameter (45.0 +/- 15.9 mm vs. 31.5 +/- 13.6 mm) and circumferential diameter (37.2 +/- 8.6 mm vs. 26.8 +/- 9.7 mm) of the resected specimens, and the proportion of extension to the whole circumference of the lumen (< 1 / 2/ > 1 / 2/ > 3 / 4 : 2 / 4 / 5 vs. 40 / 13 / 1), histologic depth (HGIN/m2 : 2 / 9 vs. 41 / 13), and procedure time (85.6 +/- 42.8 minutes vs. 53.3 +/- 30.1 minutes). Multivariate analysis revealed that circumferential extension of > 3 / 4 (odds ration [OR]: 44.2; 95 % confidence interval [CI]: 4.4 - 443.6) and histologic depth to m2 (OR: 14.2; 95 %CI: 2.7 - 74.2) are reliable risk factors. Subanalysis for each category by combinations of these risk factors revealed that patients with lesions in > 3 / 4 of the circumferential area were associated with a high rate of postoperative stricture. By contrast, patients with HGIN lesions in < 3 / 4 extension have no probability of postoperative strictures. Additionally, subanalysis of patients with m2 lesions in < 3 / 4 circumferential extension revealed that circumferential diameter can be a reliable predictor for postoperative stricture. CONCLUSIONS: Circumferential extension and histologic depth are the reliable risk factors for postoperative strictures. In combination with circumferential diameter, we can perform effective and appropriate preventive balloon dilatations after esophageal ESD.

Technical feasibility of endoscopic submucosal dissection for early gastric cancer in patients taking anti-coagulants or anti-platelet agents.

BACKGROUND: Endoscopic submucosal dissection is a novel technique that is expected to be a curative treatment for early gastric cancers. Anti-coagulants and anti-platelet agents are widely used, especially in elderly patients, to prevent thromboembolic disease. However, the feasibility of endoscopic submucosal dissection for such patients has not been investigated. AIMS: To determine the feasibility of endoscopic submucosal dissection for patients using anti-coagulant and anti-platelet agents via retrospective investigation of clinical outcomes. METHODS: Of 408 patients with 444 early gastric cancers consecutively treated by endoscopic submucosal dissection from January 2000 to December 2007 in our hospital, 47 patients with 56 early gastric cancers were receiving anti-coagulants or anti-platelet agents. All patients were classified into groups for high and low risk of thromboembolism. In 44 low-risk patients, these agents were stopped for 1 week before and after treatment. Only three high-risk patients underwent intravenous heparin replacement during the cessation period. RESULTS: Comparison with other patients showed no significant differences in complete en-bloc resection (96.4%) or perforation (1.8%). Postoperative bleeding requiring endoscopic treatment occurred for six early gastric cancers (10.7%) in the anti-coagulant and anti-platelet group; this frequency was slightly higher than that observed for other patients (5.2%). The healing of endoscopic submucosal dissection ulcers was not delayed by anti-coagulant and anti-platelet treatment (91% in the scarring stage) when checked at the 8th week after endoscopic submucosal dissection. CONCLUSION: The clinical outcomes of endoscopic submucosal dissection for early gastric cancers in patients receiving anti-coagulants or anti-platelet agents indicated that endoscopic submucosal dissection for low-risk patients could be a reliable technique with equivalent efficacy and risk in comparison with that for other early gastric cancer patients.

Contributions of social context to inequality in dental caries: a multilevel analysis of Japanese 3-year-old children.

BACKGROUND: Community context as well as individual health behavior affects oral health status. However, the contribution of social context to dental caries among people in various regions remains unclear when individual health behavior is taken into account. OBJECTIVES: To determine the influence of community context on dmft among 3-year-old children. METHODS: After all Japanese municipalities (n = 2522) had been stratified into nine regions with three caries levels, 44 municipalities were randomly selected. Community health service workers were asked to collect information on sociodemographic characteristics, oral health-related behavior, and dental condition for 3-year-old children during community dental health check-ups. Community-related variables, including socioeconomic status, social support, and social cohesion, were obtained from census data. Multilevel analysis was used to determine the effects of social context and individual behavior on dental caries. RESULTS: A total of 3301 parents (79.9%) of 3-year-old children from 39 municipalities participated in our survey, and complete information was obtained from 3086 of them. Results of the analysis showed that 90.8% (P < 0.001) of variance in dmft occurred at the individual level and that 9.2% (P < 0.001) of the variance occurred at the community level. Individual-level variables explained only 6.6% of the individual level variance in dmft. Community-level variables explained 47.2% of the community level variance. CONCLUSIONS: There are statistically significant effects of social context on dmft in municipalities in Japan.

Chemosensitization of fluconazole resistance in Saccharomyces cerevisiae and pathogenic fungi by a D-octapeptide derivative.

Hyperexpression of the Saccharomyces cerevisiae multidrug ATP-binding cassette (ABC) transporter Pdr5p was driven by the pdr1-3 mutation in the Pdr1p transcriptional regulator in a strain (AD/PDR5(+)) with deletions of five other ABC-type multidrug efflux pumps. The strain had high-level fluconazole (FLC) resistance (MIC, 600 microg ml(-1)), and plasma membrane fractions showed oligomycin-sensitive ATPase activity up to fivefold higher than that shown by fractions from an isogenic PDR5-null mutant (FLC MIC, 0.94 microg ml(-1)). In vitro inhibition of the Pdr5p ATPase activity and chemosensitization of cells to FLC allowed the systematic screening of a 1.8-million-member designer D-octapeptide combinatorial library for surface-active Pdr5p antagonists with modest toxicity against yeast cells. Library deconvolution identified the 4-methoxy-2,3,6-trimethylbenzensulfonyl-substituted D-octapeptide KN20 as a potent Pdr5p ATPase inhibitor (concentration of drug causing 50% inhibition of enzyme activity [IC(50)], 4 microM) which chemosensitized AD/PDR5(+) to FLC, itraconazole, and ketoconazole. It also inhibited the ATPase activity of other ABC transporters, such as Candida albicans Cdr1p (IC(50), 30 microM) and Cdr2p (IC(50), 2 microM), and chemosensitized clinical isolates of pathogenic Candida species and S. cerevisiae strains that heterologously hyperexpressed either ABC-type multidrug efflux pumps, the C. albicans major facilitator superfamily-type drug transporter Ben(R)p, or the FLC drug target lanosterol 14 alpha-demethylase (Erg11p). Although KN20 also inhibited the S. cerevisiae plasma membrane proton pump Pma1p (IC(50), 1 microM), the peptide concentrations required for chemosensitization made yeast cells permeable to rhodamine 6G. KN20 therefore appears to indirectly chemosensitize cells to FLC by a nonlethal permeabilization of the fungal plasma membrane.

The effect of priming techniques of ultrafiltrators on blood rheology: an in vitro evaluation.

The increased interest of using ultrafiltration during cardiopulmonary bypass ICPB) has mandated a re-evaluation of the hematological effects of this blood conservation process. 'Rinse-free' ultrafiltrators can be primed using either crystalloid or blood prior to use. It is unknown whether one priming technique results in superior results in ultrafiltration quality. An in vitro circuit was designed to evaluate the Sorin/COBE HC1400 (n=6), the Lifestream HC70 (n=6), and the Terumo/Sarns HC11 (n=6). All test conditions were conducted at a blood flow rate of 250 ml/min and a transmembrane pressure of 250 mmHg. Samples were drawn and analyzed at four distinct time points for hematocrit, total protein, plasma free hemoglobin, interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-alpha (TNFalpha). The HC11 had significantly greater percent increases in hematocrit under the blood priming protocol (29.2+/-7.9) than either the HC1400 (11.0+/-7.8, p<0.03) or the HC70 (11.9+/-7.8, p<0.04). When crystalloid priming was compared to blood priming, the HC1400 and HC70 produced significant percent increases in hematocrit and total protein levels. The HC1400 devices produced significantly less plasma free hemoglobin when primed with crystalloid rather than blood (43.6+/-38.3 vs 21.3+/-5.6, p<0.01). There were no significant differences between devices or priming techniques for IL-6, IL-8 or TNFalpha levels. In conclusion, the efficiency of the ultrafiltrators was elevated when primed with crystalloid before use. Cytokine levels were relatively unchanged with priming techniques, while plasma free hemoglobin levels were reduced with those devices previously primed with crystalloid.

Vascular invasion in squamous cell carcinomas of human oral mucosa.

The process of vascular invasion of human oral squamous cell carcinomas was histologically and immunohistochemically studied in surgical and autopsy specimens. Hematoxylin-eosin, Masson's trichrome, and immunohistochemical stainings for Ulex europaeus I lectin binding, CD31, and type IV collagen were done to differentiate lymphatic and blood vessels and to demonstrate basement membranes in vascular walls and around carcinoma cell nests was observed. With growth of tumor, there was mechanical disruption of vascular walls and endothelial cells by carcinoma cell nests. After disrupting vascular walls, they invaded into the lumen as clusters, not as single cells. At the blood vessel invasion sites, inflammatory reactions were seen around carcinoma cell nests inside as well as outside lumina with microthrombotic reactions due to endothelial injury. At the lymphatic invasion sites, carcinoma cell nests maintained their volume inside the lumen and the cells adhered tightly to each other, and inflammatory reaction was scarcely seen. These findings showed that mechanical pressure has an important role in the vascular invasion of human oral squamous cell carcinoma.

An experimental evaluation of continuous cardiotomy reservoir ultrafiltration.

Ultrafiltration has been suggested as a means to reduce the morbidity associated with blood activation. However, the application of ultrafiltration to the highly activated blood of the cardiotomy suction subcircuit has not been investigated. The purpose of this study was to determine whether cardiotomy reservoir ultrafiltration (CRUF) would be effective in altering cytokine levels. Six swine, undergoing 90 min of cardiopulmonary bypass (CPB), were divided into two groups; one group was assigned to receive CRUF (N = 3), the other was to serve as controls and did not receive ultrafiltration (N = 3). Blood samples were analyzed for hematocrit, plasma-free hemoglobin, total protein, interleukin-8 (IL-8), and tumor necrosis factor alpha (TNF-alpha). Samples were taken pre-bypass, postheparinization, every 30 min during CPB, post-CPB and postprotamine. All data were analyzed using a one-way analysis of variance (ANOVA), with significance accepted at p < .05. There were no significant differences found between treatment and control groups for plasma-free hemoglobin levels (22.4 +/- 22.2 vs. 14.6 +/- 14.4; 40.1 +/- 26.1 vs. 40.0 +/- 19.3). After 90 min of ultrafiltration, there was a significant decrease in TNF-alpha (261.6 +/- 119.6 vs. 71.8 +/- 11.4; p = .02). Although IL-8 levels decreased from throughout the experiment, concentrations did not reach statistical significance. In conclusion, CRUF can be used without increasing cellular destruction, and can decrease certain cytokine levels. Our results suggest that further clinical studies should be undertaken utilizing this technique with a larger sample size.

Intra-operative quality assessment of coronary artery bypass grafts.

Early coronary artery bypass graft (CABG) failure is a troubling complication that may result in a wide range of problems, including refractory angina, myocardial infarction, low cardiac output, arrhythmia, and fatal heart failure. Early graft failures are related to poor quality and size of the distal native vascular bed, coagulation abnormalities, or technical problems involving the graft conduits and anastomoses. Unfortunately, graft failure is difficult to detect during surgery by visual assessment, palpation, or conventional monitoring. We evaluated the accuracy and utility of a transit-time, ultrasonic flow measurement system for measurement of CABGs. There were no differences between transit-time measurements and volumetric-time collected samples in an in vitro circuit over a range of flows from 10 to 100ml/min (Bland and Altman Plot, 1.96 SD). Two hundred and ninety-eight CABGs were examined in 125 patients. Graft flow rate was proportional to the target vessel diameter. Nine technical errors were detected and corrected. Flow waveform morphology provided valuable information related to the quality of the anastamosis, which led to the immediate correction of technical problems at the time of surgery.

The effects of continuous blood gas monitoring during cardiopulmonary bypass: a prospective, randomized study--Part I.

The use of continuous in-line blood gas management (CILBGM) is steeped in controversy concerning its potential utility and impact on patient outcomes. The purpose of this study was to determine whether the use of CILBGM results in improved quality of patient care. Fifty-nine patients were enrolled in a Institutional Review Board-approved, prospective, randomized study. An in-line blood gas monitor (CDI 500) was placed into the arterial and venous lines for all patients. Blood gas monitoring in the control group was managed by intermittent sampling (every 20-30 min), while the treatment group was managed with continuous monitoring. There were no differences between groups in preoperative, surgical, anesthetic, or perfusion variables. The accuracy of the in-line monitor was comparable to laboratory analysis for arterial blood gas parameters (N = 160; pH bias = 0.00; PaCO2 bias = -1.1 mmHg; and PaO2 bias = 0.7 mmHg). There was less deviation from target values (pH = 7.40, PaCO2 = 40 mmHg, PaO2 = 150-200 mmHg) when in-line monitoring was used versus intermittent sampling (N = 784; pH deviation = 0.05 +/- 0.03 vs. 0.03 +/- 0.01, p < 0.0001; PaCO2 deviation = 4.0 +/- 2.9 mmHg vs. 2.0 +/- 0.9 mmHg, p < 0.0001; and PaO2 deviation = 22.7 +/- 16.9 mmHg vs. 11.7 +/- 8.3 mmHg, p < 0.0001). In conclusion, the results of part I of this study demonstrate that the use of CILBGM results in more accurate blood gas management during CPB.

The effects of continuous blood gas monitoring during cardiopulmonary bypass: a prospective, randomized study--Part II.

The impact of blood gas management during cardiopulmonary bypass (CPB) on patient care has not been examined and remains controversial. The purpose of this study was to determine whether precise blood gas management during CPB influences patient outcome. Fifty-nine patients were enrolled in an Institutional Review Board-approved, prospective, randomized study. An in-line blood gas monitor (CDI 500) was placed into the arterial and venous lines for all patients. Blood gas monitoring in the control group was managed by intermittent sampling (every 20-30 min), while the treatment group was managed with continuous monitoring. Blood gas control and measured parameters were as follows: pH 7.40 +/- 0.05, PaCO2 40 +/- 5 mmHg, PaO2 200 +/- 50 mmHg. The treatment group had the CDI 500 guide clinical decisions. Compared to the control group, the treatment group consisted of significantly more diabetic (7% vs. 47%, p < or = 0.001), renal failure (3% vs. 13%, p < or = 0.01), and chronic obstructive pulmonary disease patients (7% vs. 20%, p < or = 0.01). Internal thoracic artery utilization was higher in treatment patients than control patients (67% vs. 95%, p < or = 0.02). No other differences existed in demographic, pharmacological, surgical, or anesthetic parameters. In the perioperative period, the control group required antiarrythmic support more frequently than the treatment group (10% vs. 0%, p < or = 0.05). Compared to the control group, the treatment group required antiarrythmic (18% vs. 10%, p < or = 0.05) and cardiac glycoside therapy (11% vs. 0%, p < or = 0.05) less frequently in the postoperative period. Although treatment patients required less intraoperative pacing and cardioversion and spent less time on mechanical ventilation, in the intensive care unit (ICU), and in the hospital than control patients, statistical significance was not achieved. In conclusion, the use of continuous, in-line blood gas monitoring resulted in improvement in a number of postoperative outcome variables, although ICU and hospital stay was not effected.

Role of catalase in retinal antioxidant defence system: its comparative study among rabbits, guinea pigs, and rats.

The role of catalase in the retinal antioxidant defence system was examined in rabbits, guinea pigs, and rats with and without prolonged administration of a diet containing 0.4% 3-aminotriazole (3-AT), a catalase inhibitor. When weanling rabbits, guinea pigs, and rats we administered 3-AT for 8, 7, and 10 weeks, respectively, retinal catalase activity was reduced by approximately 50% in all these animals. In the retina of rabbits with 3-AT administration, a decrease in superoxide dismutase (SOD) activity and an increase in lipid peroxide (LPO) concentration occurred. while glutathione peroxidase (GSH-px) activity did not change. In the retina of guinea pigs with 3-AT administration, an increase in LPO concentration occurred, while SOD and GSH-px activities did not change. In the retina of rats with 3-AT administration, a decrease in GSH-px activity and an increase in LPO concentration occurred, while SOD activity did not change. An increase in serum LPO concentration was found in rats with 3-AT administration, while the concentration did not change in rabbits and guinea pigs. These results indicate that catalase plays an important role in the retinal antioxidant defence system, but that the way catalase contributes to the maintenance of the retinal antioxidant defence system is different among these animals. The present results suggest that under the prolonged inhibition of catalase, the retina of rats, but not of rabbits and guinea pigs, may suffer from the influence of systemic oxidative stress.

Molecular cloning and expression of the Candida albicans beta-N-acetylglucosaminidase (HEX1) gene.

beta-N-Acetylglucosaminidase was purified from the spent culture medium of Candida albicans A72 grown in the presence of N-acetylglucosamine (GlcNAc). The N-terminal amino acid sequence of the protein was determined, two degenerate oligonucleotide probes were constructed, and a 3.9-kb BamHI fragment of DNA that hybridized to both probes was subcloned from a lambda EMBL4 library of C. albicans A72 genomic DNA. This fragment of DNA contained the entire beta-N-acetylglucosaminidase (HEX1) gene, which consisted of an open reading frame coding for a polypeptide precursor of 562 amino acids with a putative 22-amino-acid leader sequence. The deduced HEX1 amino acid sequence showed similarity to hexosaminidases from a variety of organisms. Growth of C. albicans on GlcNAc induced transcription of HEX1, resulting in increased specific beta-N-acetylglucosaminidase activity. HEX1 mRNA (2.35 kb) from GlcNAc-grown cells was approximately 200 bp larger than HEX1 mRNA from cells grown on glucose. This size difference was suggested to result from the use of alternative transcription termination sites. The cloned HEX1 gene introduced into C. albicans SGY-243 on a plasmid also responded to GlcNAc induction.

Glucocorticoid-induced changes in the quantity and secretory capacity of individual rat somatotropes.

Chronic glucocorticoid treatment is complicated by growth failure. The study presented here was designed to investigate the effect of cortisone on growth hormone (GH) secretion by individual pituitary cells in young male rats. Beginning at 37 days of age, animals were injected sc with cortisone acetate (CORT; 5.0 mg/rat per day) or the same volume of saline (SAL) for 8 days. At 45 days of age, the body weights of the CORT animals (134.5 +/- 5.5 g) were significantly less (P < 0.0005) than those of SAL controls (179.3 +/- 4.2 g). The secretory capacity of dispersed pituitary cells was assessed by the reverse hemolytic plaque assay. Cells were exposed to six concentrations of GH-releasing hormone (GHRH) ranging from 0.01 to 3.0 nM. CORT treatment significantly decreased the absolute number of somatotropes per pituitary gland (CORT, 1.23 +/- 0.03 x 10(6); SAL, 1.57 +/- 0.09 x 10(6); P = 0.025). Conversely, the mean plaque areas were significantly greater for CORT animals at all concentrations of GHRH tested, indicating that the amount of GH secreted by individual somatotropes was significantly increased by CORT. It was concluded that the paradoxical increase in the in vitro GHRH responsiveness, which is commonly observed after glucocorticoid treatment, was due to an increase in the capacity of fewer individual somatotropes to secrete GH.

Peutz-Jeghers syndrome associated with adenocarcinoma of the cecum and focal carcinomas in hamartomatous polyps of the colon: a case report.

We report herein a case of Peutz-Jeghers syndrome associated with an adenocarcinoma of the cecum and four focal cancers arising in hamartomatous polyps of the colon. There were a total 27 polyps in the intestine; 4 in the small intestine and the rest in the large intestine. The hamartomatous polyps in which the 4 focal cancers were found showed no component of adenoma, and the other polyps removed from the colon and small intestine at the same time were all hamartomas with no evidence of dysplasia or malignancy. This case was rare in that multiple focal cancers may have arisen directly from the hamartomous polyps of the colon.

[A calcified mucinous adenocarcinoma of the stomach--case report].

The paper discusses the case of a 44-year-old woman with an epigastric discomfort at Hiroshima University Hospital. A barium study of the stomach showed rigidity and a giant fold. A subsequent abdominal roentgenogram and CT disclosed calcification throughout the stomach wall. Thus, is hopes of effecting a cure, a total gastrectomy, a partial resection of transverse colon, a splenectomy and a pancreatic tail resection were performed. A surgical specimen macroscopically presented an inelastic and thickened wall of the entire stomach, and deposits of whitish calcium were visible within the gastric wall. The pathological diagnosis indicated a mucinous adenocarcinoma, se, INF alpha, v2, ly3, n4 (No. 221), with calcification of this mucinous adenocarcinoma in the stomach.

The indications of chemosensitivity tests against various anticancer agents.

In order to determine the indications of chemosensitivity tests against various anticancer agents, clinical trials of 4 different assays, namely; nude mouse isotope assay (NMIA), subrenal capsule assay (SRCA), human tumor clonogenic assay (HTCA) and adenosine triphosphate inhibition assay (ATPA), were performed on 391 patients. Analysis of the correlation between assay results and clinical effects presented the possibility of determining the indications as follows; (1) The positive clinical response of mitomycin C (MMC) should be predicted by ATPA; (2) The clinical tumor resistance against MMC should be predicted by SRCA; (3) Concerning 5-fluorouracil (5-FU) the chemosensitivity test (ATPA) should only be used for the detection of tumor resistance in the assay; (4) The poor results of this study indicated the difficulty of correctly estimating the effects of cyclophosphamide (CPM); (5) The perfect prediction of clinical effects in this trial indicated that cis-DDPlatinum (CDDP) should be estimated by SRCA; (6) The positive clinical tumor response against adriamycin (ADM) should be predicted by SRCA, while the negative one should be predicted by HTCA; and (7) ATPA showed good potential for estimating not only time dependent drugs such as 5-FU, but also cytotoxic drugs.

[Combined effects of interferon alpha-A/D with fluoropyrimidine derivatives in the subrenal capsule assay].

The combined effects of interferon alpha-A/D (IFN alpha-A/D) with 5-fluorouracil and fluoropyrimidine derivatives such as 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur), UFT, 1-hexylcarbamoyl-5-fluorouracil (HCFU) and 5'-deoxy-5-fluorouracil (5'-DFUR), were examined by 4-day subrenal capsule assay. Four human tumor xenografts serially transplanted in athymic mice, H-111, SH-10 established from gastric cancers, CH-4 and CH-5 from colon cancers, were used. In this experiment, the adequate dose of each agent was estimated as 50 mg/kg for 5-FU, 473 mg/kg for tegafur, 433 mg/kg for UFT, 50 mg/kg for HCFU, 185 mg/kg for 5'-DFUR and 1 x 10(5) IU for IFN alpha-A/D, respectively. When synergistic, additive and subadditive effects were defined as positive combined effects, all combinations produced positive combined effects against H-111 and CH-5, while negative ones were observed for all combinations against CH-4. The combinations of 5-FU, HCFU and 5'-DFUR with IFN alpha-A/D produced synergistic effects against SH-10. These results indicate that the combination therapy of 5-FU and fluoropyrimidine derivatives with IFN alpha-A/D would be useful.