Biomedical subjects

S Fushida

Publications and source records attributed to S Fushida.

88 records · Page 5Linked to original sources

PubMedDate not supplied

Neoadjuvant chemotherapy for high-grade advanced gastric cancer.

Fifty-five patients with high-grade advanced gastric cancer in whom the presence of stage IV was confirmed by preoperative diagnostic imaging were treated with PMUE therapy by a combined use of cisplatin (CDDP) 75 mg/m2, mitomycin C (MMC) 10 mg/body, etoposide 150 mg/body, and UFT (a combination of 1-(2-tetrahydrofuryl)-5-fluorouracil and uracil in a molar ratio of 1:4) 400 mg/day. CDDP and MMC was administered intravenously on the first day, followed by etoposide 50 mg/day on the 3rd, 4th, and 5th days. All the patients had measurable lesions that were evaluated by computed tomography scanning before and after the treatments. These patients were allocated randomly to two groups. Of these cases, 29 belonged to the neoadjuvant chemotherapy (NAC) group to whom PMUE therapy was given preoperatively; the remaining 26 patients underwent operation first and received PMUE thereafter (control group). Background factors did not differ significantly between the two groups. The response rate was higher in the NAC group than in the control group (62% in the former versus 35% in the latter). The resectability rates were 79% and 88% in the NAC and control groups, respectively. However, the rate of potentially curable cases was higher in the NAC group than in the control group (38% in the former versus 15% in the latter). Among the nonresection cases, the prognosis was highly unfavorable in both groups. In the resection cases, however, the survival rate was significantly better in the NAC group than in the control group. These results may indicate that in patients with high-grade, advanced gastric cancer initial chemotherapy (neoadjuvant chemotherapy) and then surgery should be considered.

Adenocarcinoma↗

PubMedDate not supplied

Hyperthermo-chemotherapy combined with cytoreductive surgery for the treatment of gastric cancer with peritoneal dissemination.

Continuous hyperthermic peritoneal perfusion (CHPP) with anticancer agents (mitomycin C and cisplatin) in warm saline was performed in patients with peritoneal dissemination of gastric cancer following resection of the primary lesion. The effect of CHPP was examined by a second-look operation. This study includes 41 cases of gastric cancer with peritoneal dissemination but without liver metastasis treated during the past 6 years. The overall median survival was 14.6 months to 64.2 months from CHPP to death and the 3-year survival rate was 28.5%. Second look surgery revealed a remarkable diminution in the degree of peritoneal dissemination in 7 (50%) of 14 patients with disappearance of ascites after only one course of CHPP in 7 (77.8%) of 9 patients. Long-term 3 year-survival was noted in 4 (9.8%) patients on CHPP. Side effects were renal insufficiency in 2 (5%) patients, leukopenia in 2 (5%) patients, and perforation of the small intestine in 1 (2%) patient. These results suggest the effectiveness of CHPP in the treatment of gastric cancer with peritoneal dissemination.

Adult↗

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

Amplification of the c-erbB-2 gene in gastric carcinoma: correlation with survival.

c-erbB-2 gene amplification was examined by slot blot hybridization using DNAs extracted from formalin-fixed and paraffin-embedded tissues of primary gastric carcinomas. Eleven of the 82 carcinomas (13.4%) exhibited amplification. Twenty-eight carcinomas (34.1%) expressed c-erbB-2 protein immunohistochemically. All of the tumors with amplified c-erbB-2 genes had expression of c-erbB-2 protein. The incidence of diploid and aneuploid tumors with c-erbB-2 gene amplification was similar. The survival rate was significantly lower in cases with c-erbB-2 gene amplification. Furthermore, patients with tumors showing a combination of c-erbB-2 gene amplification and DNA aneuploidy had the poorest prognosis. c-erbB-2 gene amplification may be an important prognostic indicator in gastric carcinomas.

Adenocarcinoma↗

PubMedDate not supplied

Prediction of lymph node metastasis and prognosis from the assay of the expression of proliferating cell nuclear antigen and DNA ploidy in gastric cancer.

Cell proliferation of 174 specimens obtained from the primary gastric cancers using endoscopic biopsy was investigated by immunohistochemical analysis with the monoclonal antibody PC10, which recognizes a proliferating cell nuclear antigen (PCNA) in formalin-fixed and paraffin-embedded material. All the examined samples showed nuclear staining for PCNA in cancer cells. The investigation was to test the correlation between PCNA labeling and lymph node metastasis. DNA aneuploidy was often encountered in tumors with nodal involvement and lymphatic invasion. The logistic regression analysis identified PCNA labeling rates (LRs), tumor size, and macroscopic type as independent significant factors for lymph node metastasis. When the PCNA LRs and clinicopathologic parameters were entered into the Cox regression analysis, PCNA LRs and DNA ploidy emerged as independent significant prognostic factors. In addition, combination assay of PCNA LRs and DNA ploidy yielded a powerful prognostic indication for patients with gastric cancer.

Bromodeoxyuridine↗

PubMedDate not supplied

Amplification of epidermal growth factor receptor gene and its relationship to survival in human gastric cancer.

The correlation between the clinical features in 103 patients with primary gastric carcinoma and amplification of epidermal growth factor receptor (EGFR) gene was analyzed retrospectively. EGFR gene amplification was examined by slot-blot hybridization using DNA extracted from formalin-fixed, paraffin-embedded tissues. EGFR expression was also examined immunohistochemically using the same tissues with a monoclonal antibody that is monospecific for EGFR. In 5 of 103 cases (4.9%), a 2- to 11-fold amplification of EGFR gene was detected. Four of these 5 cases were poorly differentiated adenocarcinomas. All of them had overexpressions of EGFR. The cumulative survival rate of patients with EGFR gene amplification was significantly lower than that of the patients without amplification (p < 0.05) and all of them died within 3 years. Except for tumor size (p < 0.03), there were no significant clinicopathologic differences between the two groups. On the other hand, 41 of 103 cases (39.8%) exhibited expression of EGFR. However, there was no significant correlation between EGFR expression and clinicopathologic factors or prognosis. These results indicate that EGFR gene amplification may occur in advanced stages during the progression and be an important indicator of poor short-term prognosis in gastric carcinoma.

Adult↗

PubMedDate not supplied

Evaluation of p53, Ki-67 and DNA ploidy in both primary rectal carcinomas and locally recurrent tumors.

The object of this study was to evaluate cellular markers which included tumor cell p53 expression, cell proliferation antigens and DNA ploidy in both primary and locally recurrent rectal cancer. The study included 16 locally recurrent rectal cancer and 24 non-recurrent primary rectal cancer. Levels of p53 and Ki-67 expression were quantified and the DNA ploidy analyzed. In the locally recurrent group, labelling index of p53 was significantly higher in the short disease-free interval (DFI) (<2 years) group than the long DFI (> or = 2 years) group (p<0.05). It was immunohistochemically proved that DNA aneuploidy was reflected by accumulation of mutated p53 in both primary rectal cancer and locally recurrent tumors. The early local recurrence after curative operation for rectal cancer was associated with the number of p53 positive cells.

Adult↗

PubMedDate not supplied

Immunohistochemical study of MT-MMP tissue status in gastric carcinoma and correlation with survival analyzed by univariate and multivariate analysis.

Matrix metalloproteinase (MMP) expression is associated with advanced-stage cancer and contributes to tumor progression, invasion, and metastasis. Membrane type matrix metalloproteinase (MT-MMP) has a potential transmembrane domain at the C terminus and activates pro-MMP-2, which is mainly produced from interstitial fibroblasts. Its expression on the membrane of invasive tumor cells results in the pericellular space degradation at cell-matrix contact sites and renders cancer cells more invasive at the migration front. To elucidate the relationship between MT-MMP expression and metastasis and prognosis in gastric cancer patients, MT-MMP expression was analyzed immunohistochemically in 127 primary tumors and results were correlated with several prognostic parameters and patient's survival. MT-MMP immunoreactivity was stained on the cell membrane of cancer cells and fibroblasts in the invasion front. MT-MMP was detected in 72 tumors (57%) (MT-MMP-positive). MT-MMP expression was closely associated with macroscopically invasive type, nodal involvement, lymphatic invasion, vessel invasion, and peritoneal dissemination. Patients with MT-MMP-positive tumor had a significantly worse prognosis than those with MT-MMP-negative tumor (p<0.001). Multivariate analysis showed MT-MMP overexpression as an independent prognostic factor in gastric cancer patients. Immunohistochemical analysis for MT-MMP may be an indicator of metastatic potential or the prognosis of gastric cancer patients.

Adult↗

PubMedDate not supplied

Subtotal peritonectomy with chemohyperthermic peritoneal perfusion for peritonitis carcinomatosa in gastrointestinal cancer.

Treatment for peritonitis carcinomatosa in gastrointestinal cancer remains to be established though it is one of the commonest causes of cancer death. Subtotal peritonectomy (SP) with chemohyperthermic peritoneal perfusion (CHPP) was developed for the new therapeutic strategy for peritoneal dissemination in gastrointestinal cancer in our department. SP includes resection of stomach, colon, small bowel, spleen, gall bladder, and parietal peritoneum. CHPP was carried out by heated saline containing 25 mg/l cisplatin, 10 mg/l mitomycin C, and 20 mg/l etoposide. Intraperitoneal temperature was maintained at 42 degrees C for 60 min. Fifteen gastric cancer and three colon cancer patients with severe peritoneal dissemination underwent these procedures. The averages of operating time, intraoperative bleeding volume, and total perioperative transfused blood volume were 9 h, 4400 ml, and 5600 ml, respectively. The patients estimated as complete resection and residual disease by histopathological study numbered 11 and 7. There was no treatment-related deaths though bleeding occurred in 5 patients; perforation in 2 patients; and abscesses in 2 patients. The 1-year survival rate (1ysr) and the 2-year survival rate (2-ysr) of all the patients were 57% and 21%, respectively. The 1-ysr and the 2-ysr of the patients who underwent complete resection were 67% and 40% significantly greater than the 43% and 0% of the patients who had residual tumors (p=0.02). The combination therapy of SP and CHPP is feasible in spite of its morbidity and has great possibilities in complete resection of peritoneal dissemination and prolongation of patient's survival.

Adult↗

PubMedDate not supplied

A new surgical approach (peritonectomy) for the treatment of peritoneal dissemination.

BACKGROUND/AIMS: Despite the improvements of chemotherapy and surgical techniques, treatment results of peritoneal dissemination still remain pessimistic. METHODOLOGY: During a 10-year period, 106 patients with peritoneal dissemination from gastric cancer were treated with chemo-hyperthermic peritoneal perfusion (CHPP), peritonectomy + CHPP, systemic PMUE therapy, and surgery alone in 51, 15, 13, and 27 patients, respectively. In peritonectomy, disseminated nodules were resected as much as possible in combination with the combined resection of the abdominal organs and parietal peritoneum covering diaphragm, pelvis and abdominal wall. After resection, the abdominal cavity was treated with heated saline at 42-43 degrees, containing cisplatinum (CDDP), Mitomycin C (MMC), and etoposide for 1 hour. PMUE therapy was administered with one course of i.v. infusion of 75 mg/m2 of CDDP and 30 mg/body of MMC on the 1st day, followed by etoposide 50 mg/body on the 3rd, 4th, and 5th day, and with oral intake of 400 mg/body of UFT every day from the 1st day. RESULTS: No post-operative or chemotherapeutic deaths were observed. Systemic PMUE therapy showed no survival improvement, and survival of the peritonectomy + CHPP group was the best, following CHPP, systemic PMUE and surgery alone. CONCLUSIONS: Peritonectomy and CHPP may be the best choice for the treatment of peritoneal dissemination.

Adult↗

PubMedDate not supplied

Chemohyperthermic peritoneal perfusion for peritoneal dissemination in various intra-abdominal malignancies.

A total of 25 patients with severe peritoneal dissemination underwent chemohyperthermic peritoneal perfusion (CHPP). The primary tumors in these patients comprised colorectal cancer (n = 14), ovarian cancer (n = 6), cervical cancer, (n = 1), small bowel cancer (n = 1), pseudomyxoma retroperitonei (n = 1), cystoadenocarcinoma of liver (n = 1), and pancreas cancer (n = 1). The intraperitoneal perfusion was carried out with a magnet pump for 60 min. The heated perfusate contained anticancer drugs to act synergistically with the hyperthermia. The intraperitoneal temperature was maintained at 42.0-42.5 degrees C. Eight of 25 patients showed CR, four PR, ten NC, and three PD, and the percentage (CR+PR) representing the overall efficacy rate was 48.0%. The morbidity rate was 8% (2/25) and there was no treatment-associated mortality. The percentage (CR+PR) of the patients with colorectal cancer was 57%; ovarian cancer, 50%; and other malignancies, 20%. The 1 year-and 3 year-survival rates of all the patients were 55% and 26%, respectively. The median survival periods of the CR, PR, NC, and PD groups were 4.0, 1.0, 1.0, and 0.7 years, respectively. The survival curve of the CR group was the best of all the groups (P = 0.02). These results indicated that CHPP was a feasible therapy and exerted a direct anticancer effect on peritoneal dissemination especially in the case of ovarian cancer, and the prognosis of complete responders was improved.

Abdominal Neoplasms↗

PubMedDate not supplied

Postoperative results of left upper abdominal evisceration for advanced gastric cancer.

BACKGROUND/AIMS: In spite of the improvement of surgical techniques, the prognosis of patients with advanced gastric cancer still remains poor. With the aim of achieving en bloc resection of primary tumor, peritoneal dissemination on the greater omentum and lymph node metastasis, left upper abdominal evisceration (LUAE) was performed for 75 patients. In this report, we investigated the prognostic difference between the LUAE group and standard gastrectomy (total gastrectomy + pancreatosplenectomy). METHODOLOGY: In the LUAE group, total gastrectomy was performed with the en bloc resection of the transverse colon, pancreas body and tail, spleen and left adrenal gland. In addition, omental bursa, covering retroperitoneum and pancreas body and tail was resected in combination with greater omentum, transverse mesocolon, and lesser omentum. RESULTS: There were 3 (4.1%) postoperative death in the LUAE group, and 2 (1.7%) in the control group. However, there was no statistical difference in the incidence of postoperative complications between these 2 groups. The overall 5-year survival rates of the LUAE and control groups were 33% and 39%, respectively. There was no statistical survival difference between these 2 groups. Survival difference between the LUAE and control group was not found in terms of tumor location, wall invasion, lymph node status, peritoneal dissemination, and macroscopic type. CONCLUSIONS: From these results, LUAE cannot improve the survival of patients with advanced gastric cancer. Consequently, LUAE should be indicated for T4 tumors, which directly invade into the transverse colon.

Adrenalectomy↗

PubMedDate not supplied

Intraoperative chemohyperthermic peritoneal perfusion as an adjuvant to gastric cancer: final results of a randomized controlled study.

BACKGROUND/AIMS: Although the most frequent cause of death after curative resection of advanced gastric cancer is peritoneal recurrence, there was no effective therapy for the prevention of peritoneal recurrence. This randomized trial sought to determine whether intraoperative chemohyperthermic peritoneal perfusion could eliminate microscopic residual disease and thereby improve survival of patients with advanced gastric cancer. METHODOLOGY: One-hundred and thirty-nine patients with T2-4 gastric cancer underwent curative gastrectomy with extended lymphadenectomy. These patients were randomly allocated into the following three groups. Patients in the CHPP group received surgery + chemohyperthermic peritoneal perfusion, and those in the CNPP group underwent surgery + chemonormothermic peritoneal perfusion. The third group was surgery alone group. In the CHPP and CNPP groups, peritoneal cavity was perfused with 6-8 liters of heated saline at, respectively, 42-43 degrees C and 37 degrees C with 30 mg of mitomycin C and 300 mg of cisplatin by a extracorporeal circulation machine. RESULTS: Major operative complication occurred in 19% (9/48), 14% (6/44) and 19% (9/47) of the CHPP, CNPP and surgery alone group, respectively. Complication which uniquely developed after chemohyperthermic peritoneal perfusion was bowel perforation. Mortality rates of each group were 4% (2/48), 0% (0/44) and 4% (2/47) in the CHPP, CNPP and surgery alone group, respectively. Overall 5-year survival rates of CHPP, CNPP and surgery alone groups were 61%, 43% and 42%, respectively. In a subset analysis, patients with gastric cancer having serosal invasion or lymph node metastasis have shown a statistically significant improvement in survival when treated with chemohyperthermic peritoneal perfusion. However, chemonormothermic peritoneal perfusion had no survival benefit. By analyzing with Cox proportional hazard model, chemohyperthermic peritoneal perfusion emerged as an independent prognostic factor for good survival. Surgery alone had three-fold higher risk of death than chemohyperthermic peritoneal perfusion. CONCLUSIONS: Chemohyperthermic peritoneal perfusion had an efficiency for the prophylaxis of recurrence after curative resection of advanced gastric cancer, and is indicated for patients with tumor infiltrating beyond serosal layer and node positive tumor.

Chemotherapy, Adjuvant↗

PubMedDate not supplied

Expression of insulin-like growth factor-2, c-MET, matrix metalloproteinase-7 and MUC-1 in primary lesions and lymph node metastatic lesions of gastric cancer.

BACKGROUND/AIMS: Lymph node metastases are thought to be formed as lymphatic flow, so the first metastasis is formed in the lymph node nearest the primary tumor and then further lymph node metastases are formed continuously down stream. In this study of gastric cancer, we evaluated whether IGF-2 (insulin-like growth factor-2), c-MET (hepatocyte growth factor receptor), MMP-7 (matrix metalloproteinase-7) and MUC-1, which are associated with nodal metastasis from primary tumor, are concerned with metastasis from nodal metastatic lesion to other nodes. METHODOLOGY: Tissue specimens were obtained from 146 patients who underwent gastrectomy at the Department of Surgery II of Kanazawa University between 1989 and 1997. We evaluated the expression of IGF-2, c-MET, MMP-7 and MUC-1 in 146 primary tumors and 66 metastatic lymph nodes by immunohistological staining. RESULTS: In primary lesions, these 4 factors had significant association with lymphatic vessel infiltration and MMP-7 and MUC-1 had significant association with nodal metastases. In nodal metastatic lesions, positive rates of MMP-7 and MUC-1 were higher than in primary lesions. Furthermore, 37 (73%) of the 51 cases with positive staining for MMP-7 in metastatic lesions in perigastric lymph nodes and 5 (33%) of the 15 cases without the staining had nodal metastases in group 2 or more, showing significant difference (P < 0.05). And 37 (76%) of the 49 cases with positive staining for MUC-1 in metastatic lesions in perigastric lymph nodes and 5 (29%) of the 17 cases without the staining had nodal metastases in group 2 or more, showing significant difference (P < 0.01). CONCLUSIONS: MMP-7 and MUC-1 were associated with not only nodal metastasis from primary tumor but also metastasis from nodal metastatic lesion to other nodes.

Adenocarcinoma↗

PubMedDate not supplied

Surgical treatment of advanced gastric cancer with metastasis in para-aortic lymph node.

We have studied the incidence and prognosis of N4 node (para-aortic lymph node) metastases in gastric cancer in 434 patients who had been referred to our department for surgical treatment during the period between 1978 and 1988. N4 nodal involvement was found in 76 (17.5%) of 434 patients who had received a laparotomy with resection, and in 42 (10.5%) of 400 patients who had "curative" resection. When the surgeon assessed that the patients had metastasis in para-aortic lymph nodes, the para-aortic lymph nodes lying above and below the left renal vein were completely removed (R4 gastrectomy). During this period, 42 patients with N4 nodal involvement underwent "curative" resection by R4 gastrectomy. Their treatment results were compared with those of 32 patients who underwent subtotal or total gastrectomy (R2 or R3 gastrectomy) without resection of metastases of para-aortic lymph nodes ("palliative" resection). The operating time and the operative mortality rate were similar in both groups (R4 vs R2 or R3 gastrectomy). The patients who had undergone "curative" resection (R4 gastrectomy) had a significantly higher five-year survival rate than those who had received "palliative" resection. The R4 gastrectomy is a rational and useful surgical procedure for treating patients with N4 nodal involvement.

Carcinoma↗

PubMedDate not supplied

Correlation of the histological effects and survival after neoadjuvant chemotherapy on gastric cancer patients.

BACKGROUND/AIMS: The surgical results for patients with stage IV gastric cancer are very poor. This study was performed to clarify the morphologic changes and survival after neoadjuvant chemotherapy for the stage IV gastric cancer patients. MATERIAL AND METHODS: Forty-three patients with stage advanced gastric cancer were treated with preoperative PMUE therapy by a combination use of cisplatin 75 mg/m2, mitomycin C 10 mg/body, etoposide 150 mg/body and UFT 400 mg/day. Among them, 32 patients underwent gastrectomy. Resected specimens were precisely examined histologically, and the histologic changes were correlated with clinical response and survival. RESULTS: Histologic manifestations of neoadjuvant chemotherapy included coagulation necrosis of cancer cell, appearance of the giant cell with foamy degeneration, extracellular mucin pools, aggregates of foamy histiocytes and/or stromal fibrosis. Histological responses were obtained in 24 (75%) of 32 primary tumors, 13 (81%) of 16 liver metastases, 20 (76%) of 28 lymph node metastases and 3 (18%) of 17 peritoneal disseminations, respectively. Clinical responses were observed in 21 (49%), but there was no statistical survival difference between clinical responders and nonresponders. In contrast, histologic responders survived significantly longer than non-responders. CONCLUSIONS: These results indicate that the grading of the histologic changes is a good prognosticator of patients treated with neoadjuvant chemotherapy, and yields an important information for the selection of postoperative chemotherapy.

Adenocarcinoma↗