Continuous hyperthermic peritoneal perfusion (CHPP) with a solution which contains 30 mg mitomycin C and 300 mg cisplatin has been introduced as a prophylactic treatment for peritoneal recurrence after curative resection of 79 advanced gastric cancers. The control group consisted of 81 patients with advanced gastric cancer who underwent curative surgery during the same period. CHPP was performed for 60 minutes by perfusing MMC- and CDDP-containing saline solutions warmed at 43.5 degrees C by a special CHPP device. In patients with pathologically confirmed serosal invasion-positive tumors, the survival rate of the CHPP group was significantly higher than that of the control group. A survival advantage for stage IV patients was also obtained by CHPP. However, there was no survival advantage between the CHPP group and the control group with serosal invasion-negative tumors. Adverse effects were observed in four patients who underwent CHPP: One developed severe bone marrow suppression, and transient hyperazotemia was observed in the other three. There was no difference in the incidence of mortality and morbidity between the two groups. These results indicate that CHPP is a safe, readily available prophylactic therapy for peritoneal recurrence after gastric cancer surgery.

Antineoplastic Combined Chemotherapy Protocols↗

PubMedDate not supplied

Vitamin K deficiency and osteopenia in disuse-affected limbs of vitamin D-deficient elderly stroke patients.

Bone mineral density is reduced in stroke patients on the hemiplegic and contralateral sides, reflecting a degree of paralysis and vitamin D deficiency. Because the deficiency of vitamin K, a factor essential for site-specific carboxylation of bone Gla protein, is also associated with reduced bone mineral density, an additional contribution of vitamin K to bone changes was assessed in 168 elderly patients with long-standing post-stroke hemiplegia and hypovitaminosis D. Sera were analyzed to relate vitamin K1 concentrations to bone-related biochemical indexes and bone mineral density measured by radiodensitometry of the second metacarpal. Bone mineral density was lower on both sides in patients than in the 56 controls (P < 0.02). Serum vitamin K1 concentrations, which correlated positively with bone Gla protein concentrations (P < 0.0001), were lower in patients (0.48 +/- 0.47 nmol/L) than controls (1.33 +/- 0.49; P < 0.0001). Serum bone Gla protein and 25-hydroxyvitamin D concentrations were lower in patients than controls (P < 0.0001), whereas ionized Ca concentrations were higher in patients (1.277 +/- 0.041 mmol/L) than controls (1.210 +/- 0.049; P < 0.0001), correlating with the Barthel index. Multivariate linear regression identified vitamin K1, bone Gla protein, 25-hydroxyvitamin D, ionized calcium, and the Barthel index as independent bone mineral density determinants on the hemiplegic side and 25-hydroxyvitamin D, calcium, and the Barthel index on the intact side. Immobilization and vitamin K deficiency had stronger osteopenic effects on the hemiplegic side than contralaterally.

Aged↗

PubMedDate not supplied

Effect of ipriflavone on bone in elderly hemiplegic stroke patients with hypovitaminosis D.

A significant reduction in bone mineral density occurs in stroke patients on the hemiplegic side, correlating with the degree of paralysis and vitamin D deficiency due to malnutrition, sunlight deprivation, and immobilization-induced hypercalcemia, and increases the risk of hip fracture. We evaluated the effect of ipriflavone and 1alpha-hydroxyvitamin D3 [1alpha(OH)D3; vitamin D3] administration on bone mineral density preservation as compared with untreated controls. In a randomized and prospective study of 103 patients with hemiplegia after stroke (the mean duration of illness was 4.8 yr), 68 (34 patients in each group) were given 600 mg ipriflavone or 1 microg vitamin D3 daily for 12 mo, whereas the remaining 35 patients received no drug. Bone mineral density on the hemiplegic side decreased by 1.4% in the ipriflavone group, 3.8% in the vitamin D3 group, and 5.4% in the control group (P < .0001, ipriflavone v vitamin D3 and control). At baseline, all three groups of patients showed a 25-hydroxyvitamin D insufficiency, increased serum ionized calcium, and low levels of 1, 25-dihydroxyvitamin D, suggesting immobilization-induced hypercalcemia and inhibition of renal synthesis of 1, 25-dihydroxyvitamin D. After treatment, the serum 1, 25-dihydroxyvitamin D level increased by 139.9% in the ipriflavone group and by 26.9% in the vitamin D3 group. Significant decreases in the serum ionized calcium and pyridinoline cross-linked carboxyterminal telopeptide of type I collagen, and increases in parathyroid hormone and bone Gla protein were observed in the ipriflavone group, whereas no changes occurred in the other two groups. One patient in the untreated group suffered a hip fracture, compared with none in the ipriflavone and vitamin D3 groups. These results suggest that ipriflavone is more efficacious than vitamin D3 in the prevention of decreased bone mineral density in hemiplegic stroke patients because it decreases serum calcium levels through inhibition of bone resorption and cause a subsequent increase in 1, 25-dihydroxyvitamin D concentration.

Absorptiometry, Photon↗

PubMedDate not supplied

Serum copper and zinc levels in epileptic children with valproate treatment.

Valproate (VPA) induces zinc (Zn) deficiency in experimental animals, but whether VPA treatment induces deterioration of serum trace metal homeostasis in humans is uncertain. We measured serum copper (Cu) and Zn levels in epileptic children treated with VPA and/or other antiepileptic drugs (AEDs). Patients treated with VPA monotherapy had significantly lower levels of serum Cu (82.2 +/- 16.6 micrograms/dl) than normal controls (97.3 +/- 23.0 micrograms/dl). Patients treated with VPA in addition to some other AED also had significantly lower levels of serum Cu (84.8 +/- 20.0 micrograms/dl). Serum Cu concentrations in patients treated with AEDs except for VPA (87.7 +/- 19.1 micrograms/dl) were not statistically different from those of control subjects. In contrast to the reported results of animal experiments, serum Zn levels were not altered in patients with VPA treatment. Although none of our patients showed any symptoms of Cu deficiency, we should pay attention to potential Cu deficiency in patients with VPA treatment.

Anticonvulsants↗

PubMedDate not supplied

Amplification of the c-met, c-erbB-2 and epidermal growth factor receptor gene in human gastric cancers: correlation to clinical features.

We examined amplification of the c-met, c-erbB-2, and epidermal growth factor receptor (EGFR) gene in the patients with primary gastric cancer, and compared the data with clinical features in order to clarify the relationship between oncogenic abnormality and clinical features. Oncogene amplifications were examined by slot blot hybridization using DNAs extracted from formalin-fixed and paraffin-embedded tissues of primary gastric cancers. Seven of the seventy cancers (10.0%) had c-met gene amplification, nine (12.9%) had c-erbB-2 gene amplification, and six (8.6%) had EGFR gene amplification, respectively. Eighteen cases (25.7%) exhibited one or multiple oncogene amplification, and two cases (2.9%) exhibited simultaneous amplification of the three genes. The cases with c-met gene amplification tend to show invasive character and were related to peritoneal dissemination. The cases with c-erbB-2 gene amplification were related to lymph node metastasis. The cases with EGFR gene amplification had large tumors and were in highly advanced stage. The survival rate in patients with oncogene amplification was significantly lower than that in patients without amplification. Our data indicated that these genes were related to growth and metastasis of gastric cancer. Furthermore, this study about the three genes suggested that the type of activated gene might decide on the type of metastasis and clinical features.

Aged↗

PubMedDate not supplied

Comparative ultrastructural study of atypical adenomatous hyperplasia and adenocarcinoma of the human lung.

Atypical adenomatous hyperplasia (AAH) of the human lung is considered a possible precursor of pulmonary adenocarcinoma. However, its true biological significance remains to be clarified. The authors studied the ultrastructure of AAH in surgically resected lungs and compared it with that of coexisting adenocarcinoma in an effort to define the characteristic features of AAH. Ultrastructurally, AAH possessed oval to irregular nuclei with high nucleo-cytoplasmic ratio and large nucleoli. Development of cytoplasmic organelles was generally poorer in AAH than in adenocarcinoma. However, these differences became less apparent as the degree of atypia of AAH advanced. Both lamellar bodies and electron-dense granules were found in AAH as well as in adenocarcinoma. These results suggest a close relation of AAH with adenocarcinoma of type 2 pneumocyte or Clara cell type. Further, the results of immunohistochemical studies for surfactant apoprotein A, urine protein 1, cytochrome P-450s, CEA, p53, c-erbB-2, Ki67, and bcl-2 well reflected the ultrastructural findings. These results suggest, in accordance with previous studies, that AAH is a lesion closely related to adenocarcinoma. Further, AAH shares some characteristics of type 2 pneumocytes and Clara cells, implying that it might be derived from their common precursor.

Adenocarcinoma↗

PubMedDate not supplied

Highly aggressive behavior and poor prognosis of small cell carcinoma in the stomach: flow cytometric and immunohistochemical analysis.

Small cell carcinoma of the stomach has an aggressive feature, and the survival rate of the patients is poor. The purpose of this study was to determine the clinical course, and effects of histopathologic characteristics of specific tumors including DNA contents and immunohistochemical aspects in patients with small cell carcinoma of the stomach. Medical records of 8 patients who presented with small cell carcinoma of the stomach were retrospectively reviewed. Primary tumors were studied by flow cytometric analysis and immunohistochemical staining for the p53 protein, PCNA (proliferating cell nuclear antigen), factor VIII related antigen (specific for endothelial cells), VEGF (vascular endothelial growth factor) and PD-ECGF (platelet-derived endothelial cell growth factor). DNA aneuploid was observed in 4 cases. Staining for the p53 product was positive in 50% of all the cases. The average PCNA labeling rate (LR) was 71.3+/-9.9%. Positive VEGF expression was found in 7 tumors and positive PD-ECGF expression was found in all tumors. The estimated median survival was 252 days for all the patients. Liver metastases were observed in 4 of the 8 patients, however, surgery and chemotherapy have given us one long-term survivor (43 months). Higher PCNA LR of small cell carcinoma may be an unfavorable characteristic of biological behavior. Moreover, both VEGF and PD-ECGF positivity are well-characterized inducers of hepatic metastasis.

Aged↗

PubMedDate not supplied

Apoptosis, cell proliferation and expression of oncogenes in gastric carcinomas induced by preoperative administration of 5-fluorouracil.

The purpose of this study was to examine the correlations among enhancement of apoptosis, cell proliferation and expression of oncogenes in gastric carcinomas induced by preoperative oral administration of 5-fluorouracil (5-FU). The occurrence of spontaneous apoptotic cell death in 42 patients with gastric carcinoma was analyzed in the biopsy specimens preoperatively. p53 status was examined by polymerase chain reaction-single strand confirmation polymorphism and sequencing. Fourteen patients received oral administration of 5-FU at 300 mg/body/day for 7 days preoperatively. For detection of apoptotic cells, apoptotic incidences (AIs) were examined by the terminal deoxynucleotidyl transferase-mediated deoxy-uridine triphosphate biotin nick end labeling method, on gastric carcinoma lesions based on the endoscopic findings before administration in the biopsy and resected tissues. Expressions of p53, Bcl-2, Bax gene and proliferating cell nuclear antigen (PCNA) were also examined by immunohistochemical staining. On preoperative biopsy, p53 point mutation was observed in 14 of the 42 tumors. The immunohistochemical staining status and point mutation of p53 gene (positive or negative) were identical in 32 of the 42 tumors (76.2%). The average AIs of the biopsy specimens were 1.58+/-1.26% on p53-negative staining (n=19) and 1.14+/-1.02% on p53-positive staining (n=23), a significant association was not recognized between p53 expression and AI. In the preoperative administration group, the PCNA labeling index was significantly higher in the biopsy specimens than in the resected tissues (43. 6+/-12.8% vs. 35.3+/-8.8%, p<0.01). In addition, postoperatively, the rate of AI was significantly more accelerated in p53-negative staining (n=6) than in p53-positive staining (n=8) (0.89+/-0. 65%right curved arrow 4.18+/-3.26%, p<0.05 vs. 1.20+/-0.60%right curved arrow 2.60+/-2.60%, NS). There was no significant correlation between AI and Bcl-2 or Bax staining. Immunohistochemical analysis of p53 and PCNA stainings in biopsy specimens appears to be a well-characterized indicator of sensitivity of chemotherapy in gastric carcinomas.

Apoptosis↗