Biomedical subjects

M Ikeguchi

Publications and source records attributed to M Ikeguchi.

140 records · Page 8Linked to original sources

PubMedDate not supplied

Prognostic factors in patients with advanced gastric cancer treated by noncurative resection: a multivariate analysis.

BACKGROUND/AIMS: The relationship between prognostic factors and survival time after noncurative gastric resection in patients with advanced gastric cancer was examined by a retrospective review of data on 364 patients. METHODOLOGY: There were 168 patients without metastasis to the liver or peritoneum (group A), 127 with peritoneal metastasis and no liver metastasis (group B), 50 with liver metastasis and no peritoneal metastasis (group C) and 19 with synchronous liver and peritoneal metastases (group D). Patients were primarily treated with the following 3 drugs: the fluorinated pyrimidines, cisplatin, and mitomycin C. RESULTS: Patients in group D had a very poor prognosis as compared with the other groups. Multivariate analysis using the Cox's proportional hazard model adjusted for sex, age, and other covariants indicated that lymph node metastasis, lymph node dissection, and fluorinated pyrimidines for group A, cisplatin for group B, and lymph node dissection for group C were independent prognostic factors. An analysis of patients excluding cases who died within 30 days after surgery revealed that lymph node dissection for group A, lymph node dissection and cisplatin for group B, and lymph node dissection for group C were independent prognostic factors. CONCLUSIONS: Treatment protocol specific for the residual disease may improve the survival of patients with advanced gastric cancer treated by noncurative resection.

Aged↗

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Postoperative morbidity and mortality after gastrectomy for gastric carcinoma.

BACKGROUND/AIMS: Surgical technique and postoperative care for gastric cancer have significantly improved in recent years. However, whether postoperative morbidity or mortality rates after gastrectomy for gastric cancer were reduced or not in recent years was unclear. In this study, we analyzed the chronological changes of postoperative morbidity and mortality rates, and we analyzed risk factors for postoperative morbidity and mortality in patients undergoing gastrectomy for carcinomas of the stomach. METHODOLOGY: A total of 887 patients with gastric cancer were gastrectomized in our hospital between January 1985 and December 1996. The patients were divided into three groups on the basis of chronology. The first group included patients treated over the period 1985 to 1988 (n = 324); the second group, 1989 to 1992 (n = 300); and the third group, 1993 to 1996 (n = 263). Postoperative morbidity rates and mortality rates were compared among the three groups. Also, significant risk factors affecting postoperative morbidity and in-hospital mortality were analyzed by the multiple logistic regression analysis. RESULTS: Postoperative complications were detected in 95 patients (10.7%) and in-hospital mortality rate was 2.4% (21/887). Postoperative morbidity rates were 10.5%, 11%, and 10.6% in the first, second, and third groups, respectively and postoperative mortality rates were 2.5%, 2%, and 2.7%, respectively. These postoperative morbidity and mortality rates were not different between the groups (P = 0.979 and P = 0.866). The most common postoperative complication was anastomotic leakage (56/95, 58.9%). Significant risk factors affecting in-hospital mortality were Stage IV (P = 0.006) and noncurative gastric resection (P = 0.004). However, the extent of lymph node dissection, combined resection, or the existence of preoperative complications were not significant risk factors of in-hospital mortality by multiple logistic regression analysis. CONCLUSIONS: These results indicate that patients with far-advanced gastric cancer might have a high risk of postoperative mortality. In noncurative operations for patients with advanced gastric cancer, unnecessary lymph node dissection or combined resection should be avoided.

Adult↗

PubMedDate not supplied

Thymidine phosphorylase activity in liver tissue and its correlation with multifocal occurrence of hepatocellular carcinomas.

BACKGROUND: In hepatocellular carcinoma (HCC), new tumors develop in the residual liver within a few years after hepatectomy. However, the biological risk factors of multifocal occurrence of cancers remains unclear. In this study, the thymidine phosphorylase (TP) activity, which is known as an angiogenic factor, of cancerous and non-cancerous liver tissues in HCC was analyzed to determine its suitability as a biological marker of the multifocal occurrence of HCCs. MATERIALS AND METHODS: Fresh tissues (tumor: HCC and adjacent liver tissue: N-HCC) from 63 patients with HCC and normal liver tissues (NL) from 6 patients without HCC were obtained. The TP activities of the tissues were analyzed by an enzyme-linked immunosorbent assay (ELISA). RESULTS: The mean TP activity of 63 HCCs (136 U/mg protein) was higher than that of 63 N-HCCs (81 U/mg protein) and that of 6 NLs (47 U/mg protein, p < 0.001). Multifocal occurrence of HCCs were detected in 17 patients. In these 17 patients, the mean TP activity of HCCs (145 U/mg protein) was not different from that of HCCs from the remaining 46 patients (133 U/mg protein, p = 0.272), however the mean TP activity of N-HCCs (110 U/mg protein) was significantly higher than that of N-HCCs from the remaining 46 patients (71 U/mg protein, p = 0.038). Moreover, only a high TP activity of N-HCCs was detected as a significant risk factor of multifocal occurrence of HCCs. CONCLUSION: Patients who have tumors with high TP activity in the non-cancerous livers may have a risk of multifocal occurrence of HCCs in the residual liver.

Adult↗

PubMedDate not supplied

Relationship between the cell-proliferative activity of gastric cancers and that of the normal epithelium.

Samples of gastric carcinomas and of normal gastric mucosa adjacent to tumors from 104 patients with primary mucosal gastric cancer were analysed by flow-cytometry. These patients were divided into two groups according to the histologic type of their tumors (differentiated group and undifferentiated group). The pattern of DNA ploidy and the sizes of the S- and G2M-phase fractions (percentages of cells at each respective phase) were compared between these two groups. DNA aneuploidy was encountered in 25.4% of the cases in the differentiated group and in 21.2% of the cases in the undifferentiated group. The mean sizes of S- and G2M-phase fractions of carcinomas in the differentiated group were 8.85% and 3.75% and they were significantly higher than the mean sizes of S- and G2M-phase fractions of carcinomas in the undifferentiated group (6.97% and 2.92%). Moreover, the S-phase fraction of normal gastric mucosa adjacent to the differentiated adenocarcinoma was 5.75% and this value was significantly higher than that of normal gastric mucosa adjacent to undifferentiated adenocarcinoma (4.80%). These results suggest that the proliferative activity of mucosal gastric cancer cells, as described by flow-cytometry, is higher in cases of differentiated adenocarcinoma than in cases of undifferentiated adenocarcinoma, and that the proliferative activity of normal cells in the gastric mucosa close to where adenocarcinoma develops is higher in cases of differentiated adenocarcinoma than in cases of undifferentiated adenocarcinoma. Thus, differentiated adenocarcinoma seems to develop from gastric mucosa with high proliferative activity.

Adenocarcinoma↗

PubMedDate not supplied

Relationship between area of serosal invasion and intraperitoneal free cancer cells in patients with gastric cancer.

This study, we evaluated the relationship between the macroscopic area of serosal invasion by gastric carcinoma and the incidence of intraperitoneal free cancer cells which were detected by lavage of the Douglas cavity. Between 1976 and 1989, 362 patients with advanced gastric cancer (t3, t4) were gastrectomized and intraperitoneal free cancer cells were recognized in 119 patients (32.9%). Only 17.3% of patients with an area of serosal invasion of less than 10 cm2 had free cancer cells in their peritoneal cavities, however, 68.5% of patients with an area of serosal invasion greater than 20 cm2 had free cancer cells. Even, if curative surgery was performed for patients with free cancer cells, their five-year survival rate was very poor. The five-year survival rate of patients with curatively operated gastric cancer without free cancer cells was 49.3%, however that of patients with free cancer cells was significantly lower (15.4%, P < 0.01). Even when we are not able to receive the cytologic diagnosis for intraperitoneal free cancer cells during the operation, patients with macroscopic areas of serosal invasion greater than 20 cm2 may have free cancer cells in a very high percentage. They should be treated with effective adjuvant chemotherapy the soon after the operation to prevent peritoneal metastatic recurrence and to prolong survival.

Aged↗

PubMedDate not supplied

Relationship between hematogenic metastasis of gastric cancer and the maximum extent of venous invasion by cancer cells in the gastric wall.

BACKGROUND/AIMS: The prognosis or the incidence of hematogenic metastasis after operation in patients with gastric cancer with venous invasion by cancer cells is still unclear. MATERIALS AND METHODS: The correlation was examined between venous invasion by gastric cancer and the occurrence of hematogenic metastasis in patients with gastric cancer at stage t2 (tumor had invaded muscularis propria or subserosa). RESULTS: The incidence of venous invasion by cancer cells in 228 patients with t2 gastric cancer was 53.5%, as determined histologically. Between 1977 and 1993, 32 of these 22 patients died from hematogenic metastasis. Thirty of the 32 patients (93.8%) with hematogenic metastasis had evidence of venous invasion by cancer cells of the gastric wall. Furthermore, 17 of the 30 patients (56.7%) had venous invasion at the subserosal layer of the stomach (ssv). However, of 196 patients without hematogenic metastasis, 92 patients had venous invasion and only 8 of 92 patients (8.7%) had ssv. The mean maximum extent of ssv in 8 patients without hematogenic metastasis was 2.28 mm but it was 4.76 mm in 17 patients with hematogenic metastasis (P = 0.028). CONCLUSION: Thus, the hematogenic metastasis of gastric cancer was very closely related to the presence of extensive venous invasion by cancer cells of the subserosal layer in the gastric wall.

Adenocarcinoma↗

PubMedDate not supplied

Synchronous and metachronous primary malignancies in organs other than the stomach in patients with early gastric cancer.

BACKGROUND/AIMS: We investigated the outcomes of patients with early gastric cancer, with special reference to the prognosis of patients with synchronous or metachronous primary malignancies in organs other than the stomach. PATIENTS AND METHODS: Among 890 patients with early gastric cancer, 97 (10.9%) had synchronous or metachronous primary malignancies in organs other than the stomach. Ten-year survival rates were compared between patients who had additional malignancies and patients who had early gastric cancer but no other malignant disease (control group). RESULTS: Synchronous primary malignancies were detected in 32 patients and metachronous primary malignancies were detected in 65 patients (17 had developed before gastrectomy and 48 developed after gastrectomy). Hepatic cell carcinoma, lung cancer and colorectal cancer were frequently detected between 2 and 24 years after gastrectomy. The 10-year survival rate was 80.8% for 769 patients in the control group but it was only 49.7% for the 92 patients with additional malignancies. Moreover, metachronous malignant disease was found more over 10 years after gastrectomy in 30 of the 48 cases (62.5%). CONCLUSIONS: These results suggest the importance of long-term follow-up for detection of metachronous carcinomas at sites other than the stomach for patients with early gastric cancer.

Cause of Death↗

PubMedDate not supplied

The proliferative activity of cancer cells at the invasive margin of a tumor is a good indicator of the prognosis of patients with gastric cancer with serosal invasion.

The proliferative activity of cancer cells, as indicated by numbers of argyrophilic nucleolar organizer regions (AgNORs), at five sites along the invasive margin of the tumor was assessed for 65 patients with histologically proven and curatively operated gastric adenocarcinoma that had invaded the serosa. The mean number of AgNORs in cells at the invasive margin of the tumor was 4.6. Patients with high AgNOR scores (AgNOR score > or = 4.6, n = 34) had a significantly elevated frequency of lymphatic involvement (82%) as compared with patients with low AgNOR scores (AgNOR scores < 4.6, n = 31, 45%), regardless of the size and histologic type of the tumor, and the depth of invasion of the gastric wall. The 5-year survival rate of 33 patients with high AgNOR scores (22.7%) was significantly poorer than that of 31 patients with low AgNOR scores (55.4%, p = 0.024). Thus, the AgNOR score of cancer cells at the invasive margin of the tumor appears to be a good predictor of the prognosis of patients with advanced gastric cancer with serosal invasion.

Adult↗

PubMedDate not supplied

Pre-operative serum levels of CA72-4 in patients with gastric adenocarcinoma.

BACKGROUND/AIMS: A retrospective study was designed to evaluate the clinical significance of preoperative serum levels of carcino-embryonic antigen (CEA) and CA72-4 in patients with advanced gastric adenocarcinoma. METHODOLOGY: Pre-operative serum levels of CEA and CA72-4 were analyzed and compared with the proliferative activity of cancer cells, monitored in terms of the number of argyrophilic nucleolar organizer regions (AgNORs), in tumors from 153 patients with resected gastric adenocarcinoma with serosal invasion. RESULTS: Elevated levels of CEA were frequently found in patients with lymph node metastasis and liver metastasis. By contrast, elevated levels of CA72-4 were frequently found in patients with peritoneal metastasis at the time of operation. A close correlation was found between pre-operative levels of serum CA72-4 and the AgNOR scores of tumors. Even when apparently curative operations were performed, peritoneal metastasis occurred these were detected quite soon, after apparently curative operations in patients with high pre-operative serum levels of CA72-4 and tumors with high proliferative activity. CONCLUSIONS: This phenomenon might explain the poor prognosis of patients with high levels of CA72-4.

Adenocarcinoma↗

PubMedDate not supplied

Relationship between the long-term effects of intraperitoneal chemotherapy and the expression of p53 and p21 in patients with gastric carcinoma at stage IIIa and stage IIIb.

BACKGROUND: The relationship between the expression of p53 and p21 in cases of advanced gastric cancer (t3) with lymph node metastasis [n1(+) or n2 (+)] and the long-term effects of continuous hyperthermic peritoneal perfusion (CHPP) immediately after resection was evaluated. MATERIALS AND METHODS: Between 1983 and 1989, 74 patients with gastric cancer [t3, n1(+) or n2(+)] underwent curative gastrectomy and survived without postoperative complications. These patients were followed up for at least six years. RESULTS: Thirty-seven patients died from recurrence of cancer. In 34 patients who had tumors designated p53-/p21+ or p53+/p21+, CHPP reduced the percentage of patients who died from recurrence of cancer from 10/20 (50%) to 3/14 (21.4%, P = 0.184). However, in 40 patients who had tumors designated p53-/p21- or p53+/p21-, the percentage of patients who were treated with or without CHPP and died from recurrence of cancer was the same, 6/10 (60%) and 18/30 (60%). In the case of patients who had p21-positive tumors, the 5-year survival rate of 11 patients who were treated with CHPP (72.7%) was higher than that of 17 patients who were not treated with CHPP (41.2%, p = 0.027). However, in the case of patients with p21-negative tumors, the 5-year survival rate of 10 patients who were treated with CHPP (50%) was not very different from that of 28 patients who were not treated with CHPP (42.9%, p = 0.308). CONCLUSIONS: These results indicate that the CHPP might be effective in preventing the recurrence of cancer in patients with p21-positive regardless of the expression of p53.

Adult↗

PubMedDate not supplied

The correlation between the expression of p53 protein and DNA ploidy in patients with gastric cancer that has invaded the serosa.

To estimate the correlation between the expression of mutated p53 protein and the nuclear DNA ploidy of gastric cancer cells, as well as the influence of these factors on the prognosis of patients with advanced gastric cancer, we selected 161 patients with gastric cancer that had invaded the serosa and who were treated by potentially curative gastrectomy. The expression of p53 protein was detected in 95 (59%) patients and aneuploidy was detected in 70 (43.5%) patients. The percentage of tumors with DNA aneuploidy among the 95 tumors that were p53-positive was 51.6% and this percentage was significantly higher than that of tumors with DNA aneuploidy among the 66 tumors that were p53-negative (31.8%, P = 0.02). The percentage of cells in the G2M phase of the cell cycle was significantly higher in p53-positive tumors than that in p53-negative tumors (P = 0.024). The 161 patients were divided into four groups according to the expression of p53 protein and the DNA ploidy of their tumors. Patients with p53-positive tumors and DNA aneuploidy were allocated to group A (n = 49), patients with p53-positive tumors and DNA diploidy were allocated to group B (n = 46), patients with p53-negative tumors and DNA aneuploidy were allocated to group C (n = 21), and patients with p53-negative tumors and DNA diploidy were allocated to group D (n = 45). The 5-year survival rate of group D was 73.7% and it was significantly higher than that of group A (41.8%, P = 0.007). These observations indicate that mutated p53 protein might accelerate cell proliferation. Moreover, analysis of both p53 status and DNA ploidy of tumors seems to provide very important information for evaluation of the prognosis of patients with advanced gastric cancer.

Adult↗

PubMedDate not supplied

Hypotonic intrapleural cisplatin chemotherapy as treatment for pleural carcinomatosis in an experimental model.

An experimental model of intrapleural (i.pl.) chemotherapy using hypotonic solutions of sodium chloride was developed as a treatment for malignancies in the pleural cavity. In the current study, isotonic (308 mOsm/L), hypotonic (154 mOsm/L) and super-hypotonic (62 mOsm/L) solutions that contained equal amounts of cisplatin (CDDP) were prepared for an evaluation of their therapeutic efficacy and the pharmacokinetics of the drug. After the i.pl. injection of solutions of CDDP into mice with i.pl. tumors, we found that the amount of platinum taken up by tumor cells was significantly higher as the osmolarity of the solution was reduced. Hypotonic conditions continued for 1 hour after i.pl. injection of hypotonic solution. The maximum concentration (Cmax) and the area under the curve of concentration versus time (AUC) for platinum in the plasma was significantly higher in rats given CDDP in a hypotonic solution than in rats given the drug in an isotonic solution. The duration of survival of ddy mice with i.pl. tumors that were given i.pl. CDDP in solutions of lower osmolarity was significantly longer than that of mice given CDDP in an isotonic solution. These results indicate that use of a hypotonic solution might enhance the therapeutic efficacy of CDDP in an experimental model of pleural carcinomatosis. This procedure also seems promising as a prophylactic and therapeutic modality for treatment of patients with i.pl. malignancies.

Animals↗

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Radiochemosensitivity and expression of p53 in patients with esophageal cancer treated by absolute noncurative resection.

The aim of this study was to investigate the relationship between the expression of p53 protein and radiochemosensitivity in patients with advanced esophageal cancer. We analyzed the expression of p53 protein by an immunohistochemical method in tumors from 28 patients with advanced esophageal cancer who had been treated by absolute noncurative resection. Four patients died from postoperative complications. Fourteen of the remaining 24 patients were treated with postoperative radiochemotherapy. The expression of p53 protein was detected in tumors from 16 of 28 patients (57.1%). The mean survival period was 16.4 months for 14 patients treated with radiochemotherapy, as compared to 6.9 months for 10 patients who were not treated with radiation therapy (P = 0.112). In the case of the 14 patients treated with radiochemotherapy, the mean survival period was 24.7 months for seven patients with p53-negative tumors while it was only 8 months for seven patients with p53-positive tumors. However, difference was not statistically significant (P = 0.149). Postoperative radiochemotherapy prolonged the survival of some patients with noncuratively operated esophageal tumors that were p53-negative. However, the enhanced survival was not statistically significant.

Aged↗

PubMedDate not supplied

Expression of MAGE-1, MAGE-2 and MAGE-3 genes in human gastric carcinomas; lack of evidence for cytotoxic effects in cases with simultaneous expression of MAGE-3 and HLA-A2.

The human MAGE gene products are recognized by major histocompatibility complex-restricted cytotoxic T lymphocytes. We analyzed by RT-PCR the expression of MAGE-1, MAGE-2, MAGE-3 and HLA-A2 genes in 10 human gastric cancer cell lines and 46 human stomachs removed due to advanced gastric carcinomas. All the cell lines expressed MAGE genes, except for MKN-45 and -74 which lacked the expression of MAGE-1 and -3 genes in this study. Of the 46 gastric carcinomas, MAGE-1, -2 and -3 genes were expressed in 14 (30%), 10 (22%) and 26 (57%) cases, respectively, regardless of histological type. Normal gastric mucosa and intestinal metaplastic mucosa showed no expression of these genes. HLA-A2 gene expression was noted in 14 both normal and carcinoma cases. Simultaneous expression of MAGE-3 and HLA-A2 genes was noted in 7 cases. Mean apoptotic and Ki-67-labeling indices (AI and KI) of carcinoma cells were 2.3 +/- 0.5 and 48.1 +/- 6.0 in 7 cases, and 2.8 +/- 0.2 and 47.3 +/- 2.7 in the other 39 cases lacking the expression of MAGE-3 and/or HLA-A2 genes, respectively. The two-year survival rate did not differ between the two groups. Although this study confirmed the relatively higher expression of the MAGE gene family in human advanced gastric carcinomas, it might suggest that simultaneous expression of MAGE-3 and HLA-A2 genes does not necessarily imply the induction of cancer cell apoptosis by CTL.

Antigens, Neoplasm↗