How should pain be controlled in clinical trials for pancreatic cancer?
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Clinical Trials as Topic↗
Biomedical subjects
M Sasako
Publications and source records attributed to M Sasako.
A case of bone marrow recurrence from gastric carcinoma after a nine-year disease-free interval.
We present a case of very late and unusual recurrence of gastric cancer. Nine years following total gastrectomy for gastric carcinoma, a 57-year-old man presented with disseminated intravascular coagulation associated with bone marrow recurrence. The primary tumor was a signet ring cell carcinoma invading the subserosal layer with lymph node metastasis. The patient was treated with sequential administration of methotrexate and 5-fluorouracil and went into remission. After treatment, he survived 10 months. Autopsy revealed diffuse bone marrow infiltration and distant lymph node metastasis with signet ring carcinoma cells.
Antineoplastic Combined Chemotherapy Protocols↗
Lymph node retrieval in a randomized trial on western-type versus Japanese-type surgery in gastric cancer.
PURPOSE: In the tumor-node-metastasis (TNM) staging system, no recommendations are provided on what lymph node retrieval technique is to be used to determine lymph node status, which leads to variability in nodal status assessment and TNM staging. PATIENT AND METHODS: Lymph node retrieval was quantitated using data from 237 curatively resected gastric cancer patients, from a prospective, randomized trial that compared the Western resection with limited (D1) and the Japanese resection with extended lymphadenectomy (D2), and compared data from the literature. Moreover, the efficacy of different lymph node retrieval techniques was determined. RESULTS: The mean yield of lymph nodes was 15 in D1 and 30 in D2, which is similar to results from German investigators, but substantially lower than results from Japanese investigators (60 in D2). Use of a fat-clearance technique significantly increased (P = .01) nodal yields compared with conventional retrieval. Significantly higher yields (P < .001) were obtained by a Japanese surgeon using conventional retrieval directly postoperatively. Experience of surgicopathologic teams with processing resection specimens did not influence nodal yields. Further analysis showed that reference values for nodal yields per anatomically defined station as reported in the literature were contradicted by our results and indicated the ambiguity of such standards. CONCLUSION: Despite some anatomical variability in the distribution of lymph nodes, advice on the number of nodes to examine per N level, feasible in all patients, should be incorporated into the TNM classification to standardize nodal status assessment. Based on our findings, we advocate retrieval of nodes immediately postoperatively by the surgeon.
Europe↗
[Getting informed consent in clinical trials on Japanese cancer patients].
According to the survey in the spring, 1995 of the Minister of Health and Welfare, only 20% of recently died patients had been told the truth, having cancer, in Japan. This suggest that most of clinical trials on cancer in Japan involved patients without real Informed consent (IC) from patients themselves. Recent effort of the Japanese Clinical Oncology Group are breaking through this situation. In the first part, principles of IC in cancer patients and IC in trials were explained. Then the results of a questionnaire are shown. From my personal experience of over 700 patients told the truth, all that doctors should tell to patients in western countries could be told without causing troubles even in Japan. The results of the questionnaire answered by 388 patients of various cancers treated by the author, showed clearly the feasibility of telling the truth to Japanese cancer patients. This has long been regarded impossible or unacceptable. Only 2% of them regretted to be told the truth, only 7% did not desire to know the prognosis, more than 90% wanted to be told that they have recurrence when they would have recurrence. Even when they would be incurable, 66% of them required to be told so and only 16% did not. In such difficult situation, 36% would insist anticancer treatment, while 41% would prefer best supportive care. No one but patients themselves can make this choice.
Adult↗
Surgical treatment for gastric cancer: the Japanese approach.
Present status of gastric cancer surgery in Japan and several new procedures are reviewed in this article. Japanese treatment results of this disease were significantly better than Western results even when stages were adjusted. Generally speaking, Japanese surgical procedures are more aggressive and meticulous compared with the Western approach, and these attitudes have produced the difference in survival. Particularly, systematic lymph node (LN) dissection is included as a standard procedure, and the adjacent organs are frequently resected when tumor invades them. The latest topics in surgery are the transdiaphragmatic approach for procedures in the mediastinum, para-aortic LN dissection, computer-assisted rational lymphadenectomy, LN imaging for complete dissection, removal of the peritoneum, and hyperthermo-chemotherapy for peritoneal carcinomatosis. Consideration of postoperative quality of life (QOL) is a new trend, and many interesting procedures have been proposed to maintain QOL, such as endoscopic mucosal resection and laparoscopic wedge resection for early cancer, pylorus-preserving gastric resection to reduce dumping syndrome, pancreas-preserving total gastrectomy to reduce fistula and postoperative diabetes.
Endoscopy↗
Randomised comparison of morbidity after D1 and D2 dissection for gastric cancer in 996 Dutch patients.
For patients with gastric cancer deemed curable the only treatment option is surgery, but there is disagreement about whether accompanying lymph-node dissection should be limited to the perigastric nodes (D1) or should extend to regional lymph nodes outside the perigastric area (D2). We carried out a multicentre randomised comparison of D1 and D2 dissection. 1078 patients were randomised (539 to each group). 26 allocated D1 and 56 allocated D2 were found not to satisfy eligibility criteria (histologically confirmed adenocarcinoma of the stomach without clinical evidence of distant metastasis). Each of the remainder was attended by one of eleven supervising surgeons who decided whether curative resection was possible and, if so, assisted with the allocated procedure. Among the 711 patients (380 D1, 331 D2) judged to have curable lesions, D2 patients had a higher operative mortality rate than D1 patients (10 vs 4%, p = 0.004) and experienced more complications (43 vs 25%, p < 0.001). They also needed longer postoperative hospital stays (median 25 [range 7-277] vs 18 [7-143] days, p < 0.001). Morbidity and mortality differences persisted in almost all subgroup analyses. While we await survival results, D2 dissection should not be used as standard treatment for western patients.
Adenocarcinoma↗
Comparison of the molecular genetics of c-erb-B2 and p53 expression in stomach cancer in Britain and Japan.
BACKGROUND: Differences in the epidemiology and treatment outcome of stomach cancer have led to the suggestion that in Japan, this disease may be biologically less aggressive than that found in the West. The authors compared p53b and c-erb-B2 expression, trying to identify genetic differences in Japanese compared with Western stomach cancers. METHODS: Paraffin embedded formalin fixed tissues from 89 British and 89 matched Japanese patients were examined by immunohistochemistry after microwave treatment. Cases were matched for T-stage, year of surgery, and histopathologic grade. RESULTS: Tumors from 48 British and 46 Japanese patients expressed p53, whereas those of 27 British and 28 Japanese patients expressed c-erb-B2. No significant difference in the density or distribution of protein expression was found between the two populations. The distribution of expression between diffuse and intestinal types and the proportion of cases expressing both antigens were similar in the two groups. CONCLUSIONS: p53 and c-erb-B2 are expressed in the same way in stomach carcinomas from Japanese and British patients. This study found no evidence of genetic differences in the cancers from the two countries.
Gene Expression↗
New method to evaluate the therapeutic value of lymph node dissection for gastric cancer.
The results of 1281 potentially curative resections for advanced gastric cancer performed at the National Cancer Center Hospital between 1972 and 1986 were studied using a novel approach which circumvents the stage migration phenomenon. The incidence of metastasis and the 5-year survival rate of patients with positive nodes were calculated independently for each lymph node 'station', without any reference to overall pathological nodal stage. The therapeutic value of extended lymph node dissection was estimated by multiplication of incidence of metastasis and percentage 5-year survival rate of patients with metastasis for each station. The incidence of metastasis ranged from 2.4 per cent to 66 per cent and the 5-year survival rate of affected patients from 0 to 58.7 per cent in perigastric stations, depending on the site of the primary tumour. The incidence of metastasis was between 3.0 per cent and 44.4 per cent in the second tier of nodes (n2), and the 5-year survival rate ranged from 0 per cent to 47.5 per cent. The majority of second-tier stations showed evidence of benefit from node dissection.
Gastrectomy↗
Reevaluation of prognostic factors in gastric leiomyosarcoma.
OBJECTIVES: The aim of our study was to reevaluate the prognostic factors in gastric leiomyosarcomas, particularly those under 6 cm, which, because of improved diagnostic techniques, make up a large proportion of this series, in contrast to previously published works. METHODS: The clinicopathological features in 83 patients with gastric leiomyosarcoma were reviewed. Cox's proportional hazards regression analysis was used to determine the prognostic factors. RESULTS: Sixty of 84 leiomyosarcomas (71.4%) were less than 6 cm in diameter. In univariate analysis, the following factors were considered to be unfavorable, with statistical significances: 1) presence of distant metastasis and/or direct invasion of adjacent structures at diagnosis (hazard ratio 36.60), 2) > or = 4 mitoses per 20 high-power fields (25.39), 3) severe nuclear atypia (16.74); 4) presence of ulceration of overlying gastric mucosa (12.57), and 5) diameter > or = 6 cm (5.57). Among these factors, mucosal ulceration has been identified as a new factor associated with poor prognosis. Histologically, the tumors with ulceration showed more severe nuclear atypia (p < 0.05), necrosis (p < 0.01), and a higher incidence of mitosis (p < 0.01), compared with tumors without ulceration. In multivariate analysis, factors 1, 2, and 3 were statistically significant, although neither size nor ulceration was significant. CONCLUSIONS: The presence of distant metastasis and/or direct invasion, high mitotic rate, and severe nuclear atypia were confirmed to be unfavorable prognostic indicators. Mucosal ulceration, indicating high proliferative activity of the tumor, even if small, suggests a poor prognosis, although it was not significant in multivariate analysis.
Combined Modality Therapy↗
Hepatic resection for metastatic tumours from gastric cancer: analysis of prognostic factors.
Determinants of prognosis after hepatic resection for metastasis from gastric cancer were studied in a retrospective series of 21 patients, including four who survived more than 5 years after surgery. All patients underwent apparently curative resection. Synchronous or metachronous resection, age, sex, histological type, depth of invasion, lymphatic and venous invasion, lymph node involvement and number of hepatic metastases were analysed as prognostic factors for survival. Serosal invasion was the only significant determinant at synchronous resection. Both lymphatic and venous invasion were significant prognostic factors available after histological examination. Combined analysis of these two histological variables revealed that patients positive for both were at a significantly higher risk for both overall and disease-free survival. It is suggested that hepatic resection should be attempted in patients with synchronous or metachronous metastases if there is no serosal invasion by the primary gastric tumour, and if the primary tumour has neither venous nor lymphatic invasion in the case of metachronous metastases.
Adult↗
Evaluation of the extent of lymphadenectomy in a randomized trial of Western- versus Japanese-type surgery in gastric cancer.
PURPOSE: In the context of a prospective, randomized trial of gastric cancer treatment, comparing Western surgical resection with limited lymphadenectomy (R1) versus Japanese surgical resection with extended lymphadenectomy (R2), we analyzed adherence to the specified surgical-pathologic guidelines. PATIENTS AND METHODS: Following evaluation of 389 patients, we quantified noncompliance (ie, performance of less dissection than specified) and contamination (ie, performance of more extensive dissection than specified). Of 389 patients, pathologic data permitted identification of 237 eligible patients treated with curative intent. RESULTS: Noncompliance occurred in 84% of R1 and R2 cases, with magnitude significantly (P < .001) higher in R2 cases versus R1 cases. Contamination occurred in 48% of R1 cases and 52% of R2 cases, with the magnitude of contamination moderate and equally distributed between the two groups. The contamination in R1 resections and the noncompliance in R2 resections lead to a partial homogenization of the groups, undermining the likelihood of detecting any potential therapeutic advantage to R2 dissection. CONCLUSION: The observed tendency to perform R1 resections combined with insufficient retrieval of lymph nodes underlines the need for increased surgical-pathologic standardization in this trial. Potential remedies are discussed. Proper conduct of clinical trials requires reliable means of standardizing performance of the surgical-pathologic team, an elusive but important goal.
Adenocarcinoma↗
[Overview of clinical trials on adjuvant chemotherapy for curatively resected gastric cancer].
Reports of the results of clinical trials on adjuvant chemotherapy for curatively resected gastric cancer were reviewed. All but two trials did not show its efficacy. In spite of this, understanding some results of subset analysis as definite proof, a consensus was achieved in Japan on its efficacy due to lack of proper knowledge of medical statistics among surgeons. Recently it has been recognized that this consensus was groundless and that evaluation of adjuvant chemotherapy should be carried out again. The results of the trial of JCOG, comparing adjuvant chemotherapy versus control (surgery alone) are therefore awaited. For the moment, all clinical trials on adjuvant chemotherapy for curatively resected gastric cancer should have an arm of surgery alone as control.
Antineoplastic Combined Chemotherapy Protocols↗
Recurrence of early gastric cancer. Follow-up of 1475 patients and review of the Japanese literature.
BACKGROUND: The outcome of surgical treatment for early gastric cancer (EGC) generally is considered to be satisfactory. Although a small percentage of patients experience disease recurrence, the absolute number of such instances is too small for assessment of risk factors. METHODS: The authors investigated the follow-up records of 1475 patients with EGC treated at the National Cancer Center, Tokyo, with special reference to cancer recurrence. In addition, 20 Japanese reports on this subject were reviewed. RESULTS: Excluding operative deaths and patients with noncurative operations, 20 (1.4%) patients died of recurrent disease. The death rate associated with other causes (6.6%), including other malignant diseases, surpassed that associated with disease recurrence. Late recurrence (after 5 years) was seen in seven patients. By combining the data of patients reported in 20 articles in the literature, the authors estimated a recurrence rate for EGC of at least 1.9%, exclusive of cancers arising in the gastric stump. The incidence of recurrence was significantly higher in submucosal (3.6%), node-positive (10.7%), and histologically differentiated carcinomas (2.3%) than in mucosal, node-negative, and undifferentiated groups, respectively. Analysis of 123 instances of recurrent disease, the details of which had been reported, revealed that hematogenous metastasis was the most common mode of recurrence. The mean survival period of patients with recurrent disease was 40 months, and 23% of patients died more than 5 years after surgery. CONCLUSION: It is rare for EGC to recur, even in patients with tumors with a comparatively high risk of recurrence. Long-term follow-up of patients with positive nodes for hematogenous spread might facilitate early detection of disease recurrence.
Adenocarcinoma↗
Overexpression of c-erbB-2 protein in gastric cancer. Its correlation with long-term survival of patients.
BACKGROUND: Overexpression of c-erbB-2 protein in breast cancer has been reported to be associated with poor prognosis. However, clinical significance of c-erbB-2 protein overexpression has not been demonstrated clearly in gastric cancer. METHODS: Immunohistochemical reactivity to c-erbB-2 protein was examined in formalin-fixed, paraffin-embedded tissue sections from patients with gastric cancer. RESULTS: First, primary stomach cancers in 106 patients were examined. Among 58 cases of papillary or well- to moderately differentiated tubular adenocarcinoma, staining of c-erbB-2 protein was positive on the plasma membrane of cancer cells in 8 cases (14%). Conversely, among 47 cases of poorly differentiated adenocarcinoma or signet ring cell carcinoma, positive staining of c-erbB-2 protein was detected in one case only (2%), where the histopathologic type was poorly differentiated adenocarcinoma with a cohesive structure. Among tubular adenocarcinomas, no significant association was shown between overexpression of c-erbB-2 protein and the depth of tumor invasion, extent of lymph node metastasis, or tumor location. To investigate the correlation between the staining of c-erbB-2 protein and prognosis in gastric cancer, an additional 108 cases of papillary or well- to moderately differentiated tubular adenocarcinoma invasive as far as the muscularis propria were examined immunohistochemically for expression of c-erbB-2 protein. Twelve cases (11%) showed positive staining on the plasma membrane, and their survival curve showed a significantly poorer prognosis (P < 0.01). CONCLUSIONS: These results suggest that overexpression of c-erbB-2 protein occurs selectively in cohesive gastric cancer, and it can be considered an important prognostic indicator.
Adenocarcinoma↗
Is the prognosis for Japanese and German patients with gastric cancer really different?
BACKGROUND: Differing survival rates have been reported between patients having undergone surgical intervention for the treatment of gastric carcinoma in Japan and Western industrialized countries. Through the actual availability of the data compiled at a major Japanese medical center (National Cancer Center, Tokyo), it was possible, for the first time, to compare the patients and therapeutic results of a Japanese center (n = 1475) with that of a German center (Department of Surgery, Technical University of Munich, Munich; n = 453). METHODS: The prognostic factors involving both groups were compared. Survival rates were analyzed in univariate and multivariate fashions. RESULTS: Some of the examined prognostic factors, such as sex, histologic type, tumor size, and Borrmann classification, were similarly distributed. Differences in frequency were discovered concerning pathologic tumor (pT), node (pN), and metastasis (pM) categories, localization, and age groups. Univariate analysis showed a 2-year survival rate of 88% for all Japanese patients with gastric cancer compared with 58% for German patients. The 5-year survival rates were 77% and 44%, respectively. The difference in the 2-year and 5-year survival rates for both departments may be related to differences in frequencies of several characteristics. In performing the same analysis in a multivariate fashion for the patient populations at both centers, it became clear that an important prognostic factor was the center itself. The survival curves of patients from Tokyo and Munich with the same prognostic factors demonstrate this difference. These differences, however, were small in comparison with those of univariate analysis. CONCLUSIONS: Using a similar classification of the tumor stage and similar prognostic characteristics, the prognosis for gastric cancer in Japan and Germany may be the same.
Adenocarcinoma↗
Adjuvant therapy after curative resection for gastric cancer: meta-analysis of randomized trials.
PURPOSE: An overview is presented of reports published since 1980, in which postoperative adjuvant chemotherapy is compared with surgery alone for patients with gastric cancer. A MEDLINE literature review yielded 123 reports, 14 of which were relevant randomized trials; data from 11 of these trials were (or became) available for analysis of crude mortality odds. These 11 trials included 2,096 patients. METHODS: Odds ratios were calculated by comparing the adjuvant treatment arm with the observation-only arm. Those odds ratios that could be considered homogeneous yielded an estimated common odds ratio of 0.88 (95% confidence interval [CI], 0.78 to 1.08), which was slightly, but far from significantly, in support of adjuvant treatment. RESULTS: The results confirm the common opinion that the adjuvant chemotherapy regimens prescribed in these trials, although effective in phase II studies, do not improve survival. Furthermore they indicate that postoperative chemotherapy in general offers no additional survival benefit for patients with curatively resected gastric cancer. CONCLUSION: In conclusion, at present, postoperative chemotherapy cannot be considered as standard adjuvant treatment. New trials of adjuvant therapy for gastric cancer must include a no-treatment control arm.
Antineoplastic Combined Chemotherapy Protocols↗
Preoperative assessment of lymph node metastases in patients with gastric cancer: evaluation of the Maruyama computer program.
The probability of survival of patients with gastric cancer depends upon depth of wall penetration by the primary tumour and metastatic lymph node burden. Radical lymphadenectomy may lead to prolonged survival but with increased morbidity. A computer program from Maruyama, National Cancer Centre, Tokyo enables evaluation of individual survival time and infiltration of lymph nodes. This analysis was applied to a German population. Computer-aided predictions were determined retrospectively using the prognostic factors of sex, age, Borrmann classification, histology, depth of wall penetration, location and diameter of the tumour. Data were collected from 222 patients at the Technical University of Munich (median age 66 years, sex ratio (M:F) 2:1), who had been operated on (72 per cent total gastrectomy, 28 per cent subtotal gastrectomy) for gastric cancer. The predicted results were compared with the postoperative pathological findings. The prediction of node metastases was highly accurate (lymph nodes 13-16, 96 per cent; 7-12, 89 per cent; 1-6, 82 per cent). These computer predictions may provide perioperative information of therapeutic value.
Aged↗
R2 compared with R1 resection for gastric cancer: morbidity and mortality in a prospective, randomised trial.
OBJECTIVE: To compare the postoperative course of patients in the Dutch nationwide randomised trial of R1 (conventional) compared with R2 resection (including extended lymph node dissection) in the treatment of gastric cancer. DESIGN: Prospective randomised controlled trial. SETTING: National multicentre trial with 72 participating hospitals in The Netherlands. SUBJECTS: 192 patients who were operated on between August 1989 and May 1990. INTERVENTIONS: 96 patients were randomised for a R1, and 96 for a R2 resection. MAIN OUTCOME MEASURES: Morbidity and mortality among 131 patients (64 R1 and 67 R2) for whom the resection was performed with curative intent. RESULTS: The groups were comparable for age, sex, type of resection, site of tumour and depth of invasion. Complications developed in 23 R1 (36%) and in 29 R2 patients (43%). Seven patients died in the postoperative period. Median hospital stay was significantly longer after R2 (18 days, range 7-122) than after R1 resection (15 days, range 2-63) (p < 0.05). Morbidity and mortality among the patients whose R2 resection was done by the Japanese instructor (n = 34) did not differ significantly from those among patients operated on by the Dutch supervisors (n = 33), but those operated on by the Japanese instructor stayed in hospital significantly longer (20 compared with 16 days, p < 0.05). CONCLUSIONS: If R2 resections are carried out by properly trained surgeons under supervision, they can be done safely. The reported high morbidity after R2 resection in Western countries seems to result from a lack of proper instruction and quality control.
Adenocarcinoma↗