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[Cooperative study on surgical adjuvant immunochemotherapy for prevention of postoperative recurrence of gastric cancer (II). Cooperative study group on surgical adjuvant immunochemotherapy for prevention of postoperative recurrence of gastric cancer supported by the Ministry of Health and Welfare (Kondo's group])

A cooperative study on surgical adjuvant immunochemotherapy for prevention of postoperative recurrence of gastric cancer was carried out by Kondo's group from July 1974 to December 1977. A total of 848 patients with gastric cancer underwent curative resection were eligible. Of 848 patients, 819 cases with complete description of patient's background were evaluable: Group A (surgery + MMC + 5-FU:chemotherapy) 253 cases, group B (surgery + MMC + 5-FU + OK-432 or PSK:immunochemotherapy) 282 and group C (surgery alone) 284. The 5-year corrected survival rates of total cases using Cox's proportional hazard model were 76.2% with group A, 73.6% with group B and 73.3% with group C. And the 10-year survival rates were 67.6% with group A, 64.3% with group B and 63.9% with group C. The difference in survival rate among groups A, B and C was not statistically significant. In the evaluation of prognostic factors by Cox's proportional hazard model, level of curative resection, extent of resection, histological stage and Kajitani's classification had an influence upon survival rates, in which degrees of metastasis in lymph node and serous infiltration were also involved. The significance of postoperative adjuvant immunochemotherapy has not been clarified.

Adjuvants, Immunologic↗

[Cooperative study of surgical adjuvant chemotherapy for colorectal cancer. Cooperative Study Group of Surgical Adjuvant Chemotherapy for Colorectal Cancer in Japan].

With the cooperation of 357 institutions nationwide, during the two years from January 1984 to December 1985, curative resection cases of colorectal cancer were divided into two groups and treated in the following method: A group with chemotherapy received MMC 12 mg/m2, on the day of operation, followed by 6 mg/m2 every two months, 6 times. From the second week after operation, 800 mg/body/day of FT was administered for one year. The other was a control group with operation only. In this study, targetting those cases in which recurrence was observed within 5 years, among eligible cases histologically curative resection, recurrence forms were examined by prognostic factors and usefulness of adjuvant chemotherapy after operation. Regarding the recurrence of liver metastasis, in the case of colon cancer, the effect of chemotherapy was observed in highly positive cases of lymph node metastasis and positive cases of lymphatic vessel invasion. In rectal cancer, it was noticed in Dukes C cases. For the local recurrence of rectal cancer, it was observed in Dukes C and cases of relative curative resection. Chemotherapy tended to inhibit recurrence within one year after the operation in both liver metastasis and local recurrence.

Antineoplastic Combined Chemotherapy Protocols↗

Treatment of elderly hypertensives in Japan: National Intervention Cooperative Study in Elderly Hypertensives. The National Intervention Cooperative Study Group.

PREVALENCE OF HYPERTENSION IN ELDERLY JAPANESE PATIENTS: Data collected from post-mortem information at the Tokyo Metropolitan Geriatric Hospital showed that the overall prevalence of hypertension in Japanese patients aged over 60 years was 53%; one-third of these elderly hypertensives had isolated systolic hypertension. Isolated systolic and systolodiastolic hypertension were each associated with a similar degree of increased atherosclerosis and cardiovascular complications. In a placebo-controlled study antihypertensive treatment produced a reduction in withdrawal from treatment in elderly patients with mild hypertension. INTERIM TRIAL RESULTS: Some interim results have been obtained from a new trial which is currently under way in Japan, the National Intervention Cooperative Study for the Treatment of Elderly Hypertensives, a long-term study comparing the effects of a calcium antagonist (nicardipine) and a thiazide diuretic (trichlormethiazide) on cardiovascular complications in elderly patients with mild to moderate hypertension.

Aged↗

Influence of prerandomization (baseline) variables on mortality and on the reduction of mortality by enalapril. Veterans Affairs Cooperative Study on Vasodilator Therapy of Heart Failure (V-HeFT II). V-HeFT VA Cooperative Studies Group.

BACKGROUND: The effects of hydralazine plus isosorbide dinitrate were compared with those of enalapril in 804 men receiving digoxin and diuretic therapy for chronic congestive heart failure (CHF) in the Department of Veterans Affairs Cooperative Vasodilator-Heart Failure Trial (V-HeFT II). METHODS AND RESULTS: Patients were randomly assigned to receive 20 mg of enalapril or 300 mg of hydralazine plus 160 mg of isosorbide dinitrate daily. At 2 years, treatment with enalapril resulted in a significant (28%) reduction in mortality relative to the active control treatment. Baseline variables were examined to determine their impact on risk of mortality and on relative response to treatment. Mortality rates were significantly higher in patients with severe ventricular arrhythmias; in patients with low baseline ejection fractions, low peak oxygen consumption, and low systolic blood pressures; in patients with high cardiothoracic ratios, high scores indicating greater impairment on a quality-of-life questionnaire, and high plasma norepinephrine or renin levels; and in patients in New York Heart Association (NYHA) classes III and IV. Coronary artery disease, duration of CHF, and patient age were not predictive of mortality. Enalapril reduced mortality significantly compared with hydralazine/isosorbide dinitrate in patient subgroups with high plasma renin or norepinephrine levels and in patients with low cardiothoracic ratios. Furthermore, enalapril conferred significantly greater protection from mortality than hydralazine/isosorbide dinitrate in patients in NYHA classes I and II and in patients without arrhythmias or with < or = 10 premature ventricular contractions per hour. CONCLUSIONS: Of the prerandomization characteristics that were predictive of mortality in patients with CHF, only neurohormone measurements, cardiothoracic ratios, arrhythmia severity, and NYHA class identified subgroups of patients who benefited most from treatment with enalapril; a treatment interaction across strata was detected only for plasma norepinephrine and NYHA class. In no patient subgroup was the mortality with enalapril treatment significantly higher than the mortality with hydralazine/isosorbide dinitrate treatment.

Drug Therapy, Combination↗

Update on the Dutch Cooperative Trial: mitomycin versus bacillus Calmette-Guérin-Tice versus bacillus Calmette-Guérin RIVM in the treatment of patients with pTA-pT1 papillary carcinoma and carcinoma in situ of the urinary bladder. Dutch South East Cooperative Urological Group.

Prophylactic intravesical treatment with chemotherapeutic agents or one of the different strains of the immunomodulator bacillus Calmette-Guérin (BCG) reduces tumor recurrence and may prevent progression after transurethral resection (TUR) of superficial bladder cancer. Clinical and pathological prognostic factors are used to categorize different groups at risk for disease recurrence and progression. Solitary low-grade (G1, 2A), low-stage (pTa) tumors have less than a 5% risk of progression, while pT1 G3 tumors with concomitant carcinoma in situ (CIS) have a considerably higher risk of progression and metastases. Thus, prospective clinical trials should consider the different risks associated with different prognostic groups and stratify patients accordingly. The Dutch Cooperative Trial evaluated mitomycin versus BCG-Tice versus BCG-RIVM in 469 patients with pTA/pT1 carcinoma and CIS of the urinary bladder after TUR. Of 437 evaluable patients, 50 had CIS, 254 had pTA tumors, and 133 had pT1 tumors. No statistical differences were observed in toxicity between the two strains of BCG, but local and systemic side effects were more frequent in the BCG groups versus the mitomycin group. No differences in response rate were observed between the 3 treatment groups in patients with CIS. A statistically significant difference in favor of mitomycin was seen, however, in patients with papillary tumors. Mitomycin and BCG-RIVM were equally effective, and mitomycin proved significantly more effective than BCG-Tice. No significant difference in efficacy was observed between the two strains of BCG. Disease recurrence during the study in patients with papillary tumors was seen in 43% of mitomycin-treated patients, 64% of the BCG-Tice group, and 46% of patients treated with BCG-Rivm. However, a subgroup analysis for time to first recurrence for pTa versus pT1 and for grade 1 and 2 versus grade 3 papillary tumors showed no statistically significant between-group difference. Further studies comparing identical regimens, doses, and patient groups are needed to define more clearly which patient groups and tumors are more likely to respond to intravesical therapy.

Adjuvants, Immunologic↗

[A cooperative clinical study on the evaluation of an antibody detection test kit (MycoDot Test) for mycobacterial infections. Cooperative Study Group for MycoDot Test].

To determine the usefulness of a diagnostic kit for mycobacterial infection, we performed a five-hospital cooperative clinical study using serodiagnosis kits (MycoDot Test) to detect antibody for lipoarabinomannan (LAM) which is a membrane-derived component of mycobacterial species. We tested LAM antibody in the sera of patients with mycobacterial infection as well as healthy persons. Procedures for using the serodiagnosis kit are actually simple. Out of 130 cases of active pulmonary tuberculosis, 103 cases (79%) were positive for anti-LAM, and cases out of 24 cases of active atypical mycobacterial infection, 15 (63%) were positive. On the contrary, only 4% of healthy volunteers (1 out of 25 persons) were positive on this test. In conclusion, this diagnostic kit might be a useful test for early and supportive diagnosis of mycobacterial infections based on its sensitivity and specificity.

Antibodies, Bacterial↗

BCL-2 expression correlates with lower proliferative activity in the intermediate- and high-grade non-Hodgkin's lymphomas: an Eastern Cooperative Oncology Group and Southwest Oncology Group cooperative laboratory study.

An inverse relationship between BCL-2 expression and cell cycle transition has been suggested by recent studies in murine models. To investigate the clinical relevance of these laboratory studies, a group of 116 paraffin-embedded non-Hodgkin's lymphoma (NHL) biopsy specimens (Working Formulation Groups D-H, and J) from a cooperative group study of cellular DNA content were analyzed for the 14;18 translocation using polymerase chain reaction (PCR)-based methods and, if sufficient tissue remained, for BCL-2 and BAX expression by immunohistochemistry. The results of these studies were then compared with the results of the previously performed flow cytometric analysis of ploidy and proliferative activity (S-phase-fraction). BCL-2 expression was inversely associated with proliferative activity (P = .001; n = 41), but there was no association between staining for Bax and %S-phase. Ploidy was not associated with either BCL-2 or BAX expression. The t(14;18) was detected in 21 of the 54 cases in which PCR-amplifiable DNA was recovered; 20 of these occurred at the major breakpoint region and 1 at the minor breakpoint region. High levels of BCL-2 or BAX expression occurred independently of t(14;18). There was no association between t(14;18) and either ploidy or proliferative activity. The inverse relationship between BCL-2 expression and proliferative activity in the intermediate- and high-grade NHLs is consistent with recent studies suggesting that Bcl-2 both retards entry into the cell cycle and inhibits apoptosis.

Cell Division↗

[Shared care--integrated cooperation across the sector boundaries about patient's course. Modern health care system cooperates].

Shared care programmes have been introduced in Denmark for areas, such as diabetes, asthma, and dementia. Over a three-year period, the communication and co-operation between the health sectors have improved. Specific demands on hospital referral and discharge letters have resulted in improved quality of contents and structure. This review shows that there is limited ongoing research on shared care and that the end points including formulations like "improved co-operation" have been too broad. Almost no research is available on specific improvements obtained by shared care. The study shows that implementation of shared care research programmes with specific end points is very extensive. Only 10 per cent of the present studies have specific end points, and 75 per cent of these show positive effects of shared care programmes. The GP Consulting System in Denmark has proved most useful in the progress of shared care. Future research in shared care should focus on specific end points, in which analyses of patient's course are fundamental in an effort to obtain improvements.

Community Health Services↗