Impact on survival following successful neoadjuvant chemotherapy and radical surgery for Stage IIb bulky and Stage IIIb cervical cancer.
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Biomedical subjects
Publications and source records attributed to Y Hasuo.
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Neoadjuvant chemotherapy (NAC) is currently used for the treatment of advanced cervical cancer by many institutions. We investigated the value of NAC followed by radical surgery and/or radiotherapy for patients with locally advanced cervical cancer. Sixteen patients with stage Ib2-IIIb cervical cancer were enrolled in this study. CPT-11 (60 mg/m2) in 500 m/5% glucose was given intravenously on Days 1, 8, and 15, before cisplatin (60 mg/m2) in 500 ml normal saline. The treatment was repeated every 4 weeks for 2 or 3 cycles. All patients were evaluable for response and toxicity. Two achieved a clinical complete response (CR), 11 had a partial response (PR), 2 had no change (NC) and 1 had progressive disease (PD), for an overall response of 81.3%. Neutropenia was observed in 100% (> grade 3: 70.6%) and diarrhea was recorded in 55.9% (> grade 3: 5.9%). The combination of CPT-11 and cisplatin in locally advanced cervical cancer is thus an active regimen with a manageable toxicity as a neoadjuvant chemotherapy.
OBJECTIVES: We assessed neoadjuvant intraarterial chemotherapy (NAC) followed by radical hysterectomy and/or radiotherapy in patients with locally advanced cervical cancer. METHODS: Over 5 years, 48 consecutive women with International Federation of Gynecology and Obstetrics stage IIb-IVa cervical cancer were enrolled. Treatment consisted of bilateral internal iliac artery infusion of cisplatin (100 mg/m2, day 1) or carboplatin (400 mg/m2, day 1) and peplomycin (20 mg/m2, day 1) for two courses separated by 3 weeks. Doxorubicin (30 mg/m2, day 1) was added for patients with adenocarcinoma. Stage III patients who responded to NAC and Stage IIb patients underwent radical hysterectomy with pelvic lymphadenectomy. Stage III patients not responding to NAC and all stage IVa patients were treated with pelvic radiotherapy. RESULTS: Complete response was achieved in 5 (10.4%) of 48 patients, while a partial response was noted in 32 (66. 7%) and stable disease in 11 (22.9%). Of 25 patients with stage IIIb disease, 16 (64.0%) were able to undergo surgery. The 4-year disease-free survival (DFS) was 80.0% in patients with stage IIb and 62.3% in patients with stage III. In stage IIIb, the 4-year DFS in patients receiving surgery (75.2%) was higher than the DFS for those receiving radiotherapy (44.4%) (P < 0.05). Grade 3 or 4 leukopenia developed in 17 (35.4%) patients. Nausea and vomiting of grade 2 or higher occurred in 34 (70.8%). Creatinine clearance transiently decreased (>/= grade 2) in 16.6%. Patients negative for serum squamous cell carcinoma-associated antigen (SCC) responded better to NAC than to SCC-positive cases, and SCC-negative survival was significantly better than SCC-positive survival (P < 0.05). CONCLUSIONS: Neoadjuvant intraarterial chemotherapy with platinum was safely performed, and a survival benefit followed radical surgery with or without radiotherapy after response to NAC.
We compared the effects of nilvadipine, a calcium antagonist, and terazosin. an alpha1 blocker, on the hemodynamics and quality of life (QOL) in 12 elderly hypertensive patients with stroke. Following a washout period of 2 weeks. nilvadipine or terazosin was administered for 2 weeks in a randomized crossover manner. At the end of control and treatment periods, we measured the 24-hour-ambulatory blood pressure (BP) and postural change of BP, and interviewed QOL. Terazosin treatment did not show consistent decrease of casual BP, but was associated with a transient decrease of systolic BP and an increase of pulse rate after standing, and enhanced postprandial decrease in BP. Nilvadipine decreased casual BP in a dose-dependent manner, but showed neither postural nor postprandial change of BP. There was no difference in QOL scores with either treatment. Results suggest that nilvadipine is preferable to terazosin for the treatment of elderly hypertensive patients with stroke.
We conducted a preliminary controlled study in order to evaluate 5'-DFUR dose dependency in efficacy and safety in combination therapy of radiotherapy, 5'-DFUR and SPG for patients with uterine cervical cancer, which was regarded as suitable for cases of radiotherapy. The patients were randomly allocated into group A (5'-DFUR 600 mg/body/day) and group B (5'-DFUR 800 mg/body/day), who underwent radiotherapy with simultaneous administration of 5'-DFUR and SPG (20 mg twice/week or 40 mg/ week). Those enrolled were 33 patients in stage II, III or IV a with histologically diagnosed primary squamous cell carcinoma of uterine cervix. CR was shown in 19, PR in 7, NC in 1, and PD in 2 out of 29 efficacy-evaluable cases, so the overall response rate was 89.7% (26/29, 95% CI 72.7%-97.8%). Regarding safety, some side effects were observed in 26 out of 33 safety-evaluable cases (81.3%, 95%, CI 63.6%-92.8%), but no serious cases. No significant difference in efficacy and safety was observed between the two treatment groups. These results suggested that the combination therapy of radiotherapy, 5'-DFUR and SPG might be one of the therapies whose effectiveness must be confirmed for advanced squamous cell carcinoma of uterine cervix. To confirm dose dependency of 5'-DFUR, it seems further consideration with more patients is needed.
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It has been reported that the antitumor effect of CPT-11 is manifested through the inhibition of topoisomerase I by SN-38 which is an active metabolite of CPT-11 produced by intracellular carboxylesterase, and that CPT-11 is effective against recurrent ovarian carcinoma. We investigated the antitumor effect and adverse reactions in the combined therapy with CPT-11 and CDDP in patients with prior chemotherapy for recurrent carcinoma, and in 7 patients without prior chemotherapy, consisting of 4 patients with postoperative adjuvant chemotherapy for clear cell carcinoma and 3 patients with metastatic ovarian carcinoma. CDDP was administered on day 1 and CPT-11 was administered three times on days 1, 8 and 15. The dose of both CDDP and CPT-11 was 50 mg/m2 or 60 mg/m2. Adverse reactions were investigated in all patients and the antitumor effect was assessed in 12 patients with recurrent carcinoma who had measurable lesions. (1) The DLF was neutropenia. The neutrophil count nadiar occurred on day 18 or 19. Grade 3 or 4 adverse reactions were observed in 60% or more of the patients, but they disappeared following short term administration of G-CSF. In patients with recurrent carcinoma given CDDP and CPT-11 at 60 mg/m2, the incidence of grade 3 or 4 adverse reactions and number of occasions on which CPT-11 administration had to be postponed were higher than those in patients given 50 mg/m2. (2) Mild platelet reduction was observed. (3) Grade 3 or 4 diarrhea was observed in 3.2% of patients with recurrent carcinoma and in 7.7% of patients with metastatic ovarian carcinoma. (4) The antitumor effect was evaluated in 12 patients with recurrent carcinoma: CR in 2 patients. PR in 3, NC in 6, and PD in one. The response rate was 41.7%. (5) An antitumor effect was observed in 2 patients with serous carcinoma and in one patient each with mucous carcinoma, clear cell carcinoma and endometrial carcinoma. In conclusion, adverse reactions caused by the combination therapy with CPT-11 and CDDP (CPT-11: 50-60 mg/m2 on days 1, 8 and 15, CDDP: 50-60 mg/m2 on day 1) can be relieved by short term administration of G-CSF and it is suggested that the combination therapy may be effective in treating ovarian carcinoma.
Mass-screening for ovarian cancer by means of transvaginal ultrasonography has been performed in Aomori Prefecture since 1989. To select appropriate candidates to receive the second screening, the findings in 614 ultrasonic pictures of pelvic tumors over 30mm recorded on a VTR were studied. The results were as follows: 1) At the first screening, the rate of solid tumors was similar in each age group, but that of mixed tumors was higher in the thirties. 2) When ultrasonic findings at the first screening with that of the second screening were compared, (1) Twenty to thirty per cent of all tumors detected in the first screening had disappeared or had become under 30mm in size at the second screening. (2) About 20% of solid tumors detected in the first screening were not ovarian tumors (uterine myomas or others) in the second screening, regardless of the tumor size. (3) The rate which decided the course of therapy or follow up at the time of the second screening was not related to the ultrasonic findings for tumors smaller than 50mm. At the present time, classification of transvaginal ultrasonic findings is insufficient, and so it is difficult to use it to select appropriate candidates to receive the second screening. But the ultrasonic findings are very important in deciding on the course of therapy and follow up.
Examination of tumor markers (CAMPAS) at the second screening in our mass-screening for ovarian cancer was evaluated. CAMPAS has been performed in 866 women with enlarged ovaries over 30mm in size among 20,242 who received the first screening by transvaginal ultrasonography. In those with semi-malignant and malignant ovarian tumor (ovarian cancer), their serum levels of CA125, CEA, CA19-9, AFP and L-LDH were also measured (Combination Assay) and CA125, CEA, CA19-9, AFP, CA602, CA54 and CA61 antigens in removed tumor tissues were studied by immunoperoxidase staining (Tumor Assay). The results were as follows: 1) Ten of the 866 women were positive for CAMPAS, however, only one of them was found to have ovarian cancer. 2) Of the 20,242 women, six were found to have ovarian cancer: all in stage I and all detected among these 866 women. 3) Of the 6 women with ovarian cancer, three had high serum levels in the Combination Assay, and 4 had positive finding in the Tumor Assay, but of the 4 women with a positive Tumor Assay, one had different kinds of tumor markers in serum and one did not have a high serum level. Thus, CAMPAS was not useful as the second screening method in our mass-screening system for ovarian cancer.
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The presence of human papillomavirus (HPV) 16 in cervical intraepithelial neoplasia (CIN)II-III cases was studied by means of a polymerase chain reaction (PCR)-based method applied to paraffin-embedded tissues. Twenty-two of 45 (49%) cases showed a positive signal determined by direct visualization on gel stained with ethidium bromide. Fourteen of these cases were confirmed by dot blot hybridization, which accords with a prevalence of HPV 16 infection in 31% of Stockholm patients with CIN II-III. The latter value is lower than that published elsewhere (Young et al. 1989; Maki et al. 1991; Skydberg et al. 1991).
An exceedingly rare case of extragonadal immature teratoma, which occurred primarily in the uterus, is described. The tumor developed into the pelvic cavity from the uterine fundus and consisted of ectodermal, mesodermal and endodermal derivatives. There were also significant amounts of immature elements; immature neuroepithelium with brisk mitotic activity, immature mesenchymal tissue, immature cartilage, immature striated muscle and immature hepatic tissue. Histologically, it was classified as a grade 3 immature teratoma. Treatment consisted of total simple hysterectomy followed by 2 courses of combination chemotherapy with vincristine, actinomycin D and cyclophosphamide (VAC). The patient was well and without evidence of recurrence at 5 years post-operatively.
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Until recently, the albumin concentration of supplementation fluid for double filtration plasmapheresis (DFPP) has been empirically determined. Inadequate albumin infusion often leads to hypoproteinemic symptoms such as edema. In the current study, an aimed condensation coefficient (CCaimed) was introduced in an attempt to estimate the appropriate plasma albumin level for each patient. This coefficient is theoretically derived from a one-compartment model for the patient's plasma albumin: CCaimed = CS/CD = 1 - (1 - CR)/[1 - exp(- CC.VR)] where CD and CS are albumin concentrations in discarded plasma and supplementation fluid. CR is the change ratio of albumin concentration in the patient's plasma during a DFPP treatment, and VR(= VS/VP) is the ratio of supplementation fluid volume (VS) to the patient's total plasma volume (VP). And CC denotes the albumin condensation coefficient in a DFPP line, which depends on the filtration fraction of the plasma fractionator (FFPF) and the sieving coefficients of both the plasma separator (SCPS) and the plasma fractionator (SCPF): CC = CD/CP = SCPS.(1 - FFPF.SCPF)/(1 - FFPF) where CP is the albumin concentration of the patient's plasma. From the above relations, CS can be determined as follows: CS = CC.CCaimed.CP Because many kinds of proteins are removed during a single DFPP treatment, a slightly higher albumin concentration in the supplementation fluid is needed to maintain an appropriate plasma level. Therefore, the CR value should be more than unity. For a patient with hematocrit (HCT) of 30%, body weight (BW) of 50 kg, and CP of 3.0 g/dl, who is receiving a DFPP treatment using AP-05H (SCPS of 0.970) and Evaflux 2A (SCPF of 0.526) under FFPF of 0.8 with VS of 500 ml, VP = BW(1- HCT/100)/13 = 50 x (1 - 30/100)/13 = 2.69 L, VR = 500/(2.69 x 1,000) = 0.186, CC = 2.81, and CCaimed = 1.25 assuming 1.1 for CR. Therefore, CS = 2.81 x 1.25 x 3.0 = 10.5 g/dl using the above equations.
BACKGROUND AND PURPOSE: We sought to determine the type-specific prevalence of dementia and its risk factors in elderly persons from the Japanese community of Hisayama. METHODS: We studied the prevalence of dementia in 887 Hisayama residents (353 men and 534 women) aged 65 years or older (screening rate, 94.6%) using various items of clinical information, neurological examination, and dementia scales. We also studied brain morphology in 50 of 59 determined to have dementia by computed tomography or autopsy during the subsequent 54-month period. Factors relevant to dementia were compared between 27 patients with vascular dementia and 789 control subjects without dementia in a retrospective fashion. RESULTS: The prevalence rate of dementia among Hisayama residents aged 65 or older was estimated at 6.7%, with a females to males ratio of 1:2. Among 50 cases of dementia in which brain morphology was examined, the frequency of vascular dementia was 56%; this rate was 2.2 times higher than that for senile dementia of the Alzheimer type. Aging, hypertension, electrocardiographic abnormalities, and high hematocrit were significantly (p less than 0.05) and independently associated with the occurrence of vascular dementia. CONCLUSIONS: Prevalence of dementia among the Hisayama residents was relatively identical to that previously reported, but vascular dementia was more predominant. Risk factors for vascular dementia were similar to those for lacunar infarcts. Control of hypertension may be a key to reducing dementia among the Japanese population.
The frequency of human papillomavirus (HPV) was investigated in 245 Japanese women (100 showing normal cytology and 145 showing abnormal cytology). A previously presented method for the detection and typing of HPV DNA was used, where a dot blot test excluded samples that did not hybridize with HPV DNA. Positive samples were further analyzed by a southern blot procedure, to give the HPV type. A mixture of subgenomic probes of the types 6, 11, 16, 18, 31, 33 and 35 was used. HPV DNA was detected in only 2% (2/100) of patients without abnormal cytology. In patients with abnormal cytology, the frequency was 30% (43/145). HPV was detected in 100% (2/2) of the patients with condyloma acuminatum, 39% (26/66) of those with mild to moderate dysplasia, 44% (7/16) of those with severe dysplasia to carcinoma in situ, and 70% (7/10) of those with invasive carcinoma. Young women (20-29 yr.) had the highest HPV frequency (71%). HPV types 16 and 18 were found in 39% of the patients with mild to moderate dysplasia, in 71% of those with severe dysplasia to carcinoma in situ and in 86% of those with invasive carcinoma. These may be considered as high risk types for development to cancer. HPV type 31 may be considered as a moderate risk, as it was detected in 37% (16/43) of the patients. HPV types 6 and 11 were found in 100% of patients with condyloma acuminatum (2/2). To clarify the natural history of the HPV infection in the uterine cervix, it is necessary to conduct further studies.
Cigarette smoking as a risk factor for cerebro- and cardiovascular diseases was studied in a long-term prospective population survey which has been carried out in a Japanese rural community, Hisayama. In this population, the incidence of thrombotic brain infarction (TBI) was much higher than that of coronary heart disease (CHD) over a 26-year follow-up period. Cigarette smoking was strongly related to the occurrence of CHD but not to TBI. Comparing the incidence of CHD and TBI between first or early cohort (1961-74) and second or recent cohort (1974-87) during the 13-year follow-up, the incidence remained unchanged for CHD, while it significantly decreased for TBI in recent population. The prevalence of cigarette smoking as well as hypertension decreased in recent years, while hypercholesterolemia, obesity, and glucose intolerance increased. Smoking is a major contributor to CHD for men in both cohorts, but it is not any more for women in the recent cohort.