Biomedical subjects

R Denno

Publications and source records attributed to R Denno.

At least 37 records · Page 2Linked to original sources

PubMed1998

Development of an ulcer in the side-to-side anastomosis of a jejunal pouch after proximal gastrectomy reconstructed by jejunal interposition: report of a case.

We present herein the first reported case of a deep ulceration developing in the pouch of a jejunal side-to-side anastomosis following the interposition of a jejunal U-shaped pouch (jejunal pouch), performed as reconstruction. A 47-year-old woman underwent a proximal gastrectomy and interposition of a jejunal pouch for early gastric cancer, 4 months after which she began to develop a fever. Esophagogastroscopy revealed a deep ulceration in the side-to-side anastomosis of the jejunal pouch. Her serum gastrin level was much higher than the normal range, and 24-h monitoring of the intraremnant stomach pH revealed that it was below 7.0 at night. A peptic ulcer was thought to be one of the causes of the pouchitis. Due to the drug-resistant ulceration and fever, a reoperation was performed, in which the jejunal pouch and remnant stomach were removed and Roux-en-Y reconstruction was done. There were no postoperative complications, and the fever resolved after surgery. Reconstruction of the jejunal pouch after proximal gastrectomy is recommended from the standpoint of quality of life (QOL); however, further studies on the size of the remnant stomach and the length of the interposed jejunal pouch are necessary.

Duodenal Ulcer↗

PubMed1998

Separate functions of alpha2beta1 and alpha3beta1 integrins in the metastatic process of human gastric carcinoma.

The expression of alpha2beta1 and alpha3beta1 integrins was studied immunohistochemically in 110 resected human gastric carcinomas. Formalin-fixed and paraffin-embedded samples were serially sectioned and stained with monoclonal antibodies specifically against the alpha2 and alpha3 subunits of beta1 integrins. Approximately 27% of the tumors expressed alpha2beta1 integrin, and 20% expressed alpha3beta1 integrin. The expression of alpha2beta1 integrin was associated with lymph node and liver metastases (P < 0.05 and P < 0.05, respectively), and the expression of alpha3beta1 integrin was associated with liver and peritoneal metastases (P < 0.005 and P < 0.0005, respectively). A multivariate analysis by the logistic regression model revealed that the expression of alpha2beta1 and/or alpha3beta1 integrins was an independent factor related to liver metastasis, and that the expression of alpha3beta1 integrin was as strong an influence on the formation of peritoneal metastases as the depth of invasion. The expression of alpha3beta1 integrin also correlated with increased invasiveness of the tumor; however, there was no correlation between alpha2beta1 integrin expression and the invasiveness. These results suggest that alpha2beta1 and alpha3beta1 integrins have separate influences on the metastatic properties of cancer cells.

Extracellular Matrix Proteins↗

PubMed1998

Lack of survival benefit of extended lymph node dissection for ductal adenocarcinoma of the head of the pancreas: retrospective multi-institutional analysis in Japan.

It has not been established that extended lymph node resection is necessary for ductal adenocarcinoma of the head of the pancreas. According to the general rules for the study of pancreatic cancer, a multiinstitutional, retrospective clinical study was undertaken to investigate the efficiency of extended lymph node dissection for this malignancy. Altogether 501 patients underwent resection of the pancreas between 1991 and 1994 at 77 medical facilities; the surgical procedures, staging, lymph node dissection, curability, and survival rate were analyzed retrospectively. Eighteen of the patients died within 30 postoperative days, leaving 483 patients to be studied. The resection was curative microscopically in 94 patients, resulting in a 3-year survival of 29%. Macroscopically curative resection resulted in a 3-year survival of 14%; noncurative resection produced a 3-year survival of 6%. Although extended lymph node dissection was performed on 38 patients in stage I, 42 patients in stage II, 206 patients in stage III, and 1 patient in stage IV, there was no improvement in survival when the results were compared to those seen after standard or palliative lymph node dissection. The extent of lymph node dissection has not affected the prognosis for ductal adenocarcinoma of the head of the pancreas at any stage of the course of the disease. Excessive lymph node dissection in advanced cases does not necessarily lead to a favorable prognosis. The patients who undergo a radical operation with an adequate lymph node dissection have longer survivals.

Adult↗

PubMed1998

Biochemical modulation therapy for pancreatic cancer.

It is well known that the clinical course in most patients with advanced pancreatic cancer is not influenced substantially by chemotherapy and/or radiotherapy. However, new chemotherapy, based on the synergistic antitumor activities of 5-fluorouracil (5-FU) and cisplatin (CDDP) producing biochemical modulation in solid cancers diagnosed as adenocarcinoma, has recently been reported to be effective. In gastrointestinal cancers, the optimal concentrations of each drug and the duration of the anticancer effects, as well as adverse effects have been confirmed in pharmacodynamic studies. Our experience of this treatment for advanced pancreatic cancer (stage IV) indicates the usefulness of the antitumor effect in terms of both effect on the tumor size in unresectable patients and prognosis in resectable patients. These results were remarkable in patients diagnosed as stage IV b and/or curability C. Although there were adverse effects, none were severe. However, anything compromising the patient's quality of life must be prevented. Randomized prospective studies of the combination of 5-FU and CDDP are expected in the near future.

Adenocarcinoma↗

PubMed1998

Inhibition of liver metastasis of human pancreatic carcinoma by angiogenesis inhibitor TNP-470 in combination with cisplatin.

The anti-tumor and anti-metastatic effects of O-(chloroacetyl-carbamoyl) fumagillol (TNP-470), an angiogenesis inhibitor, and cisplatin (CDDP), an anti-neoplastic agent, were investigated using our established liver-metastasizing pancreatic carcinoma line, HPC-3H4. HPC-3H4 was injected into the spleens of nude mice. Mice were randomly divided into 5 groups; a control group given saline solution, a group receiving 45 mg/kg TNP-470, a group receiving 90 mg/kg TNP-470, a group receiving 90 mg/kg TNP-470 in combination with 0.25 mg/kg CDDP, and a group receiving 0.25 mg/kg CDDP. In the control group, liver metastasis developed in 14 of 15 mice (93.3%). Liver metastasis developed in 9 of 11 mice (81.8%) receiving 0.25 mg/kg CDDP. It developed in 11 of 15 mice (73.3%) receiving 45 mg/kg TNP-470, in 17 of 18 mice (94.4%) receiving 90 mg/kg TNP-470, and in 4 of 10 mice (40%) receiving 90 mg/kg TNP-470 in combination with 0.25 mg/kg CDDP. TNP-470 in combination with CDDP displayed a significant inhibitory effect on liver metastasis compared to the control. Although TNP-470 alone and CDDP alone had no effect on the tumor growth in vivo, 90 mg/kg TNP-470 in combination with 0.25 mg/kg CDDP had a significant effect. In vitro examinations demonstrated that the growth of HPC-3H4 cells was only mildly inhibited by TNP-470, but the production of vascular endothelial growth factor (VEGF) by HPC-3H4 was clearly inhibited by TNP-470. The inhibitory effect on the production of VEGF was not strong with CDDP treatment. These results indicate that the angiogenesis inhibitor TNP-470 in combination with low-dose CDDP has inhibitory activity against liver metastasis of human pancreatic carcinoma.

Animals↗

PubMed1998

[Clinical study of hypopharyngeal carcinoma].

A clinical study was performed of 83 patients with hypopharyngeal cancer treated in the Sapporo Medical University Hospital from 1982 to 1995. Five-year cumulative survival rate was 34.9% in the whole group and 37.2% in the radical surgical and/or radiation treatment group. In the radiation treatment group, the patients with T1, T2, N0 or N1 stage disease, especially those whose original disease responded almost completely to 40Gy irradiation, showed high tumor control rates following full-dose irradiation with or without radical neck dissection. In the radical surgery group, the patients with T4 or N2 stage disease showed better prognosis than those in the radiation group. However, among the patients with N3 lymph node metastases, there were no long-term survivors in either the radiation or the surgery groups.

Adult↗

PubMed1998

[The significance of telomerase activity in patients with gastric cancer].

The activation of telomerase is one of step in carcinogenesis. Therefore, it indicates that the detection of telomerase activity in tissues is useful for cancer diagnosis. TRAP assay developed by Kim et al. is sensitive enough to detect telomerase activity from a telomerase expressing cell. Using TRAP assay kit provided by Oncor Inc., we estimated quantitatively the telomerase activity from benign (atrophic gastritis), premalignant (intestinal metaplasia), and malignant tissues in the stomach. Telomerase activity in gastric cancer tissues was significantly higher than that in tissues which are characterized histologically as intestinal metaplasia or atrophic gastritis. In addition, to exclude interference with TRAP assay by telomerase or PCR inhibitor when telomerase activity was not observed in cancer tissues, the use of internal control (ITAS or TSNT) and dilution of samples should be performed.

Biomarkers, Tumor↗

PubMed1998

[Mechanism of the development of organ failure].

Multiple organ failure (MOF) is a critical condition developing in patients with overwhelming bodily injury resulting from major surgical insult, severe trauma, extensive burns, acute pancreatitis, and sepsis. It has recently become evident that the host response to such injury is the main pathogenetic factor contributing to the development of MOF. The proinflammatory cytokines tumor necrosis factor (TNF) and interleukin (IL)-1 are known to play a pivotal role in the pathogenetic mechanisms of MOF. In response to bodily injury, macrophages produce and release TNF and IL-1, which subsequently induce the production of other cytokines (IL-6, IL-8, etc.) and other endogenous chemical mediators. The resultant systemic inflammation may develop into MOF mainly through neutrophil-endothelial cell interaction when the primary injury is overwhelming or a second inflammatory insult such as sepsis triggers an exacerbated inflammation. It has recently been confirmed that the transcription factor NF-kappaB is involved in the up-regulation of a variety of proinflammatory genes and that cell-mediated immunity is down-regulated in the event of major bodily injury through a shift in the balance between T helper 1 (Th1) and Th2 cytokine response patterns. The molecular immunological mechanisms by which these factors participate in the development of MOF should be characterized.

Humans↗

PubMed1997

Results of 1001 pancreatic resections for invasive ductal adenocarcinoma of the pancreas.

OBJECTIVE: To evaluate the recent results of pancreatic resection in patients with invasive ductal adenocarcinoma of the pancreas. DESIGN: Retrospective study. SETTING: Seventy-seven medical facilities belonging to the Japan Society of Pancreatic Surgery. PATIENTS: One thousand one patients who underwent a resection of the pancreas between January, 1, 1991, and December 31, 1994. MAIN OUTCOME MEASURES: Morbidity and survival after surgery for pancreatic cancer according to the modified TNM classification of the International Union Against Cancer. RESULTS: After pancreatic resection, the cumulative postoperative survival rates at 1 and 3 years were 44.5% and 10.3%, respectively. Patients with early-stage cancers had a more prolonged survival time, ie, the cumulative 3-year survival rates for patients with stage I or stage II cancers were 50.4% and 45.5%, respectively; the survival rates for patients with stage III and stage IVa and IVb cancers were 17.6%, 5.7%, and 0%, respectively. The survival rate for patients with N1 or N2 metastasis did not differ appreciably, and both groups had significantly better survival rates than patients with N3 metastasis (P < .001). A significant difference in the postoperative survival time of N1 metastasis was observed between patients with no lymph node dissection (mean survival, 326.4 days) and patients who received a lymph node dissection (D1) (mean survival, 478.2 days) (P < or = .01). CONCLUSIONS: The recent results of pancreatic resection for invasive ductal adenocarcinoma of the pancreas are generally unsatisfactory. Although the outcome of the patients with an N1 metastasis can be improved if they receive N1 lymph node dissection (D1), an extensive lymph node dissection in advanced cancers does not necessarily produce a favorable prognosis.

Adult↗

PubMed1997

Close correlation between increased sialyl-Lewisx expression and metastasis in human gastric carcinoma.

Expression of sialyl-Lewisx (sLex) antigen was studied immunohistochemically in 110 resected human gastric carcinomas using an anti-sLex monoclonal antibody. Lymph node, liver, and peritoneal metastases were clearly more prevalent in tumors expressing high levels of sLex than in those with no or low-level sLex expression. No correlation was found between sLex expression and histologic grade or histologic type of the Lauren classification. Among the tumors with lymph node metastasis, 44% expressed high levels of sLex in both the primary tumor and involved lymph nodes, and 14% of the metastatic lesions demonstrated increased sLex expression. The 5-year survival rate of the patients undergoing complete (R0) gastric resections was 60% in the sLex high-expression group, which was significantly lower than that of the sLex low-expression group (81%) and of the no-expression group (87%) (p < 0.05). These results suggest that high-level sLex expression is related to both an increased risk of metastasis and poor prognosis in gastric cancer patients.

Adult↗

PubMed1997

[Bacteria isolated from surgical infections and their susceptibilities to antimicrobial agents. Special references to bacteria isolated between July 1995 and June 1996].

Isolated bacteria from infections in general surgery during the period from July 1994 to June 1995 were investigated in a multicenter study in Japan, and the following results were obtained. One hundred and sixty-four strains were isolated from primary infections, and 202 strains were isolated from postoperative infections. From primary infections, anaerobic Gram-positive bacteria were predominant, while from post operative infections, aerobic Gram-positive bacteria were predominant. Among aerobic Gram-positive bacteria, the isolation rate of Enterococcus faecalis was the highest, followed by that of Staphylococcus aureus from postoperative infections. Among anaerobic Gram-positive bacteria, the isolation rate of Peptostreptococcus spp. was the highest from both types of infections. Among anaerobic Gram-negative, Escherichia coli was the most predominantly isolated from primary infections, followed by Klebsiella pneumoniae and Pseudomonas aeruginosa in this order, and from postoperative infections, P. aeruginosa was the most predominantly isolated, followed by Enterobacter spp. and Klebsiella spp. Among anaerobic Gram-negative bacteria, the isolation rate of Bacteroides fragilis group was the highest from both types of infections. We noticed that MICs of cefazolin against three out of 23 strains of E. coli were higher than 100 micrograms/ml. Among anaerobic bacteria, there were many resistant strains against penicillins and cephems with MICs higher than 100 micrograms/ml, and the same trend was observed among other Bacteroides spp. and Prevotella spp.

Bacterial Infections↗

PubMed1997

[Isolation rate of Enterococcus spp. from surgical infections and their susceptibilities].

Enterococcus spp. isolated from surgical infections during the period from July 1982 to June 1995 were investigated in a multicenter study involving 19 hospitals in Japan, and the following results were obtained. 1. Though the isolation rate of Enterococcus faecalis and other Enterococcus spp. were not high from primary infections, and from postoperative infections the isolation rate of other Enterococcus spp. was also low, the isolation rate of E. faecalis was highest from postoperative infections after 1993. 2. Vancomycin (VCM) showed strongest activity against E. faecalis, and followed by those of ampicillin (ABPC), imipenem. levofloxacin (LVFX) and meropenem in this order. Against other Enterococcus spp., VCM showed strongest activity, and followed by those of ABPC and LVFX. There were no resistant strains against VCM.

Ampicillin↗

PubMed1997

[Combination chemotherapy of continuous infusion 5-fluorouracil and daily low-dose cisplatin in advanced gastrointestinal and lung adenocarcinoma].

Continuous intravenous infusion (c.v.i.) of 5-fluorouracil (5-FU) plus daily low-dose cisplatin (CDDP) was evaluated in 45 patients with advanced and recurrent unresected colorectal, lung, gastric and pancreatic adenocarcinoma. 5-FU was given at a dose of 320 mg/m2/day, c.v.i. for 4 weeks, and CDDP between 3.5 to 7 mg/m2/day, infused for one hour five times a week for 4 weeks. Patients received 1 to 3 cycles of treatment (average 1.5 cycle). Pancreatic cancer cases needed longer treatment periods (2.25 cycles). The response rate of colorectal cancer cases was 57.7% (15/26), pancreas cancer 40%, gastric cancer 62.5%, and lung cancer 66.7%. The overall response rate was 57.8%. No severe side effects occurred in any of these cases. These data indicate that this combination 5-FU + daily low-dose CDDP chemotherapy is effective in the treatment of advanced gastrointestinal and lung adenocarcinoma.

Adenocarcinoma↗

PubMed1996

Glutamine-enriched total parenteral nutrition enhances plasma glutathione in the resting state.

Glutathione (GSH) is the major intracellular antioxidant and is essential to normal cell function and replication. Cysteine and other thiol compounds have been considered rate-limiting for GSH biosynthesis, but recent studies have demonstrated that glutamine (GLN) becomes essential during metabolic stress to replete tissue GSH levels which have become depleted. To determine the role of GLN supplementation in the resting, nonstressed state, we studied three groups of Wistar rats. The animals were catheterized and randomly assigned to one of three groups; (1) chow ad libitum group receiving iv saline (control), (2) standard total parenteral nutrition (STA-TPN) group, and (3) glutamine-enriched TPN (GLN-TPN) group. The intravenously fed animals received no rat chow. The infusions were administered at a rate of 2.2 ml/hr for 4 days and all animals were harvested on the fifth day of study. The GLN-TPN group had a significantly higher plasma GSH level than STA-TPN or control animals (P < 0.01). The hepatic concentration of GSH and the oxidized GSH/reduced GSH were similar in all groups. GLN-TPN had a significantly lower plasma ALT level than the control group (P < 0.05). The control group had a significantly higher ALP level than STA-TPN and GLN-TPN animals (P < 0.01). There were no significant differences in other measures of hepatic functions among the three groups. Our data demonstrate that in this model GLN-enriched TPN enhances plasma GSH concentrations, while maintaining hepatic GSH stores. This suggests that GSH turnover is altered during glutamine-enriched TPN, which may explain how dietary GLN supplementation enhances tissue antioxidant capacity.

Animals↗

PubMed1996

The significance of nm23 protein expression in human gastric carcinomas.

The clinical significance of nm23 protein (nm23) expression was studied in tissue samples from 110 patients with primary gastric cancer by immunohistochemical staining with the anti-nm23 antibody. Primary carcinomas with either lymph node involvement or liver metastasis expressed significantly reduced levels of nm23 compared to those without metastasis. This relationship was clearer in the more differentiated adenocarcinomas than in the poorly differentiated adenocarcinomas. However, there was no correlation between nm23 expression and depth of invasion, quantity of stroma, infiltrating growth pattern, or macroscopic type. The cumulative 5-year survival rates based on nm23 immunoreactivity within the primary tumor were significantly higher in the nonreduced expression group (72%) than in the reduced expression group (45%). A multivariate analysis revealed that nm23 expression levels influence the outcome of patients as strongly as depth of invasion and more strongly than the other clinicopathological factors. These results suggest that the degree of nm23 expression is closely related to the metastatic potential of gastric carcinoma cells and can be used as a prognostic indicator independent of the clinicopathological features.

Adenocarcinoma↗

PubMed1996

Beneficial effects of administering intraportal prostaglandin E1 postoperatively to hepatectomy patients with massive intraoperative blood loss.

Massive intraoperative blood loss is a major cause of complications following hepatectomy. To evaluate the efficacy of intraportal prostaglandin E1 (PGE1) for preventing liver deterioration in hepatectomy patients with an intraoperative blood loss of over 2000 ml, a retrospective analysis was conducted on 10 patients given intraportal PGE1 (portal group), 6 given intravenous PGE1 (venous group), and 10 given no treatment (control group). PGE1 was infused at 250 or 500 micrograms/day in the portal group and at 720 micrograms/day in the venous group, and continued for 3 days postoperatively. Alanine aminotransferase (ALT) and total bilirubin (T.Bil) were measured on postoperative days (PODs) 1, 3, 5, and 7. ALT was lower in the portal group than in the other two groups on each POD, and significantly lower than in the control group on POD3 (P < 0.05). T.Bil was significantly lower in the portal group than in the control group on PODs 5 and 7 (P < 0.05). T.Bil on POD 7 was under 1.5 mg/dl in 1 (10.0%), 6 (60.0%), and 2 (33.3%) of the control, portal, and venous group patients, respectively, with a significant difference between the control and portal groups (P < 0.05). These results confirmed that intraportal PGE1 was beneficial for improving hepatic function and preventing cholestasis in patients with a blood loss of over 2000 ml at risk of developing postoperative liver deterioration.

Adult↗

PubMed1996

The enhanced effect of parenteral nutrition on hepatotoxicity.

Recent studies have demonstrated that enteral feedings are associated with decreased morbidity and mortality when compared with parenteral feedings. In this study, we hypothesized that (1) route of feeding affects morbidity and mortality in a model of drug-induced hepatotoxicity and (2) glutamine and polymyxin B, which have been reported to reduce bacterial translocation, attenuate this effect when TPN is used. Male virus-free Wistar rats were divided into six groups receiving: (1) ad libitum chow infused with intravenous (IV) saline (Chow), (2) standard total parenteral nutrition solution administered via gastrostomy (Enteral), (3) standard total parenteral nutrition infused via a central catheter (TPN), (4) standard TPN containing polymyxin B (TPN-PolyB), and (5) glutamine-enriched TPN (TPN-GLN). A final group of animals was not manipulated but harvested at time 0 to serve as controls. The dose of polymyxin B used in this study has previously been shown to significantly reduce bacterial translocation. After 4 d of feeding, all rats received 5% dextrose infusion after an intraperitoneal (IP) injection of acetaminophen (ACM). Rats were sacrificed 0, 6, and 24 h after ACM administration. The TPN group had a lower liver glutathione level after 6 and 24 h, greater levels of liver enzymes after 24 h, and a lower survival rate after 24 h compared with Chow. The Enteral group had less morbidity than TPN but greater morbidity than Chow. Addition of polymyxin B or glutamine had a minimal effect on morbidity or mortality when compared to the TPN group. We conclude that rats receiving IV nutrition have greater morbidity and mortality following a standard hepatic insult than chow-fed rats. We speculate that alteration of microsomal cytochrome P-450 or drug clearance may be related to the benefits of providing nutrients by the gastrointestinal route.

Acetaminophen↗

PubMed1996

Correlation between nm23 protein and several cell adhesion molecules in human gastric carcinoma.

The correlation between nm23 protein (nm23) expression and the expression of several cell adhesion molecules was studied immunohistochemically in 110 resected gastric carcinomas. Formalin-fixed and paraffin-embedded samples were serially sectioned and stained with antibodies against nm23, integrin beta1 subfamily members (alpha2beta1, alpha3beta1 and alpha4beta1), LFA-1, ICAM-1, sialyl Lewis(x) (sLex) and CD44H, -V3, and -V6. Primary carcinomas presenting with either lymph node involvement or liver metastasis expressed significantly reduced levels of nm23 compared to tumors without metastasis. The percent of tumors expressing each adhesion molecule was as follows: alpha2beta1, 27.3%; alpha3beta1, 20.0%; alpha4beta1, 14.5%; LFA-1, 14.5%; ICAM-1, 12.7%; sLex, 67.3%; CD44H, 55.5%; CD44V3, 20.0%; and CD44V6, 4.5%. Expression of alpha2beta1 integrin and high levels of sLex were significantly correlated with lymph node metastasis, and expression of alpha3beta1 integrin and high levels of sLex were correlated with liver metastasis. Expression of ICAM-1 was inversely correlated with liver metastasis. Comparing the expression of each cell adhesion molecule with nm23 immunoreactivity, expression of sLex was significantly associated with nm23 expression. Of tumors expressing high levels of sLex, 75% showed reduced nm23 expression, compared to 52% of tumors with weak or no sLex expression (P < 0.05). A similar tendency was also observed in the metastasized secondary tumors. These results suggest that reduced nm23 expression may promote the metastatic properties of cancer cells in concert with increased sLex expression.

Cell Adhesion Molecules↗