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Biomedical subjects

H Kuwano

Publications and source records attributed to H Kuwano.

At least 235 records · Page 13Linked to original sources

[Basic and clinical investigations of the effectiveness of hyperthermia combined with chemotherapy and irradiation in the treatment in patients with esophageal carcinoma].

Concomitant application of hyperthermia, bleomycin and irradiation led to a maximal effect, compared with findings in cells treated with a single or two modalities in vitro. The synergistic effect of the combination with hyperthermia and irradiation was exhibited in all layers of multicellular tumor spheroids (MTS). The combined effects of water-bath hypothermia at 42.5 degrees C for 30 min, 1/10 LD50 bleomycin iv, and 200 rad irradiation were also demonstrated in DDD strain male mice with Ehrlich ascites tumor. According to the results of in vitro and in vivo studies, hyperthermia combined with irradiation and chemotherapy was prescribed for patients with squamous cell carcinoma of the esophagus. The long term results were compared between two groups of patients treated with hyperthermo-chemo-radiotherapy and those treated with chemo-radiotherapy but not hyperthermia. The five year survival rates of patients with resectable carcinoma, given preoperative hyperthermo-chemo-radiotherapy or chemo-radiotherapy were 43.2% and 14.7%, respectively. As severe side effects in patients given hyperthermia were nil, this treatment deserves serious consideration when treating patients with a malignant lesion of the esophagus.

Animals↗

Malignant mixed mesodermal tumour of the peritoneum with a complete response to cyclophosphamide.

We treated a 66-year-old Japanese woman with malignant mixed mesodermal tumour of the heterologous type arising from the paracolic peritoneum. The tumour contained heterologous elements in the form of cartilage in addition to carcinosarcomatous areas. This is the third case of malignant mixed mesodermal tumours originating from the peritoneum to be documented in the literature. A complete resection of the tumour was carried out but multiple lymph nodes metastases in the left neck occurred 5 months later. Cyclophosphamide in doses of 150 mg daily by mouth was initiated, with the result of a complete regression of the malignant lesions. She died of myocardial infarction 21 months after surgery.

Aged↗

[Clinical evaluation of systematic lymph node dissection for the intrathoracic esophageal carcinoma].

We evaluated the effectiveness and complication of systematic lymph node dissection for the intrathoracic esophageal carcinoma, which includes cervical, intrathoracic and abdominal lymph node dissection. Two hundred and thirteen individuals with intrathoracic esophageal carcinoma underwent esophageal resection in the Department of Surgery II, Kyushu University from 1979 to 1988. Of these 213, systematic lymph node dissection in addition to esophageal resection was performed on 19 patients. Lymph node recurrence has been reduced with this procedure and survival rate was more favorable in the cases with systematic lymph node dissection than those without it at present. On the other hand, although the occurrence of postoperative recurrent nerve palsy in the cases with systematic lymph node dissection and in those without it were 47.4 and 11.9%, rates of postoperative pulmonary complications were 5.2 and 16.0%, respectively. Operative death was none in those with systematic lymph node dissection. Therefore, this procedure has been performed in safety with intensive perioperative cares and it would contribute more favorable prognosis.

Aged↗

Clinicopathologic study of early stage esophageal carcinoma.

As part of a consecutive series of 370 patients who underwent subtotal esophagectomy because of carcinoma of the thoracic area of the esophagus, between January 1965 and July 1988, in the Second Department of Surgery, Kyushu University Hospital, 42 patients (11.4%) with early stage esophageal carcinomas confined to the intraepithelium, mucosa, or submucosa were studied clinicopathologically. Of these 42, 26 (61.9%) had symptoms; slight dysphagia or chest discomfort was the most common symptom. The remaining 16 (38.1%) had no subjective symptoms. Endoscopic examination proved to be more useful than barium studies. Lugol-combined endoscopy was most effective in detecting the presence and spread of small malignant lesions of the esophagus. At the time of surgery, six patients with submucosal carcinoma of the esophagus had lymph node metastasis, and five died of recurrence. Described herein are the diagnostic features, clinicopathologic characteristics, and long-term results of these 42 patients with early stage, and 328 patients with advanced, carcinomas of the esophagus, detected and surgically treated in our clinics.

Actuarial Analysis↗

[Hyperthermo-chemo-radiotherapy of patients with carcinoma of the esophagus and prediction of the clinical remedial value using the in vitro succinate dehydrogenase inhibition test].

Hyperthermia combined with irradiation and chemotherapy was prescribed for patients with resectable (n = 88) and unresectable (n = 36) carcinoma of the esophagus. The histopathological effectiveness, and the long term results were compared between two groups of patients treated with hyperthermo-chemo-radiotherapy (HCR therapy) and those treated with chemoradiotherapy (CR therapy). A correlation between the hyperthermia sensitivity test, using the in vitro succinate dehydrogenase inhibition test, and the clinical remedial value was also examined in malignant tissues from 47 patients with esophageal cancer, and treated with HCR therapy. In the resected cases, preoperative HCR therapy resulted in a significantly higher histopathological effectiveness rate (69%) compared with that in cases treated by CR therapy (48%) (P less than 0.05). The long term results of patients with both resectable and unresectable carcinoma, given HCR therapy were significantly better than those given CR therapy (P less than 0.05). On the other hand, the clinical remedial value, determined radiographically showed a correlation rate of 77% to the hyperthermia sensitivity test. Thus, the HCR therapy resulted in not only a higher histopathological effectiveness rate but also a significantly longer survival without severe side effects, and this hyperthermia sensitivity test using the succinate dehydrogenase inhibition test facilitates prediction of the outcome of the HCR therapy.

Antineoplastic Agents↗

Intratumoural injection of calcium channel blocker enhances cytotoxicity of adriamycin in Ehrlich ascites solid tumour.

We found that the concentration of adriamycin (ADM) within the tumours were nicardipine hydrochloride (Nic) dose-dependent reaching a maximum at a Nic dose of 33.3 mg/kg body weight when Nic was injected intratumourally. In a time-course study, the maximum level of ADM after intratumoural injection of Nic was 1.3-fold higher than the maximum level with both intraperitoneal (ip) injection of Nic and ADM, but occurred later, i.e. 5 h vs 2 h respectively following exposure. Intratumoural injection of Nic prolonged the retention of ADM within the tumour, resulting in concentration levels greater than 0.5 micrograms/g of tumour, 5 to 9 h after exposure. Intraperitoneal injection of Nic and ADM and ip ADM alone resulted in peak intratumoural levels after 2 h that quickly fell after the third hour of exposure to below 0.3 micrograms/g of tumour. Furthermore, in experiments aimed at investigating the therapeutic efficacy of ADM with intratumoural vs ip injection of Nic, we found a 2.8-fold increase in the tumouricidal activity of ADM, when Nic was concurrently injected within the tumour than when it was given intraperitoneally. We conclude that intratumoural injection of Nic enhanced not only acquisition and retention of ADM by Ehrlich ascites tumour tissue, but also strengthened its tumouricidal potency.

Animals↗

Coexistence of intraepithelial carcinoma and glandular differentiation in esophageal squamous cell carcinoma.

A review of 249 cases of squamous cell carcinoma of the esophagus showed 77 cases (30.9%) with intraepithelial carcinoma contiguous to the main lesion. There were 48 cases (19.3%) with glandular and/or mucus-secreting components, in addition to the usual components of squamous cell carcinoma. Coexistence of intraepithelial carcinoma was observed in 20 cases (41.7%) among 48 with glandular differentiation, as compared with 57 cases (28.4%) without this differentiation. Of the 20 cases with glandular differentiation without preoperative irradiation, there were 16 (80.0%) containing areas of intraepithelial carcinoma. Moreover, among 77 cases with intraepithelial carcinoma, 20 (26.0%) were accompanied by glandular differentiation. Of nine tumors restricted to the mucosal or submucosal layer in 48 cases with glandular differentiation and in 44 of 203 cases without such differentiation, there were eight cases (88.9%) and 31 cases (70.5%) containing the areas of intraepithelial carcinoma, compared with rates of 30.8% and 16.6%, respectively, in the advanced carcinomas. Therefore, in the early carcinomas with glandular differentiation, there often coexist intraepithelial carcinomas. This high incidence of the coexistence of intraepithelial carcinoma and glandular differentiation, particularly in early cancers, supports the theory of a field carcinogenesis of esophageal carcinomas.

Adenocarcinoma↗

Preoperative hyperthermia combined with radiotherapy and chemotherapy for patients with incompletely resected carcinoma of the esophagus.

Two hundred eighty-nine patients with squamous cell carcinoma of the esophagus underwent subtotal esophagectomy from December 1965 to June 1986. Resection of esophageal carcinoma was absolutely noncurative in 64 patients (20%) due to invasion to the surrounding structures. These 64 patients were subdivided as follows into three groups based on the type of preoperative treatment: Group I included 16 patients without preoperative treatment; Group II included 38 patients with preoperative radiotherapy combined with chemotherapy (average doses: radiation 37.3 Gy, 1-(2-tetrahydrofuryl)-5-fluorouracil [tegafur] 8.4 g); Group III included 10 patients who underwent preoperative hyperthermia (42 degrees C to 45 degrees C) combined with chemotherapy and radiotherapy (average doses: radiation 33 Gy, bleomycin 33.9 mg, or cis-diamine dichloroplatinum 75 mg, hyperthermia 6.2 times). There were no significant differences in terms of postoperative therapy among the three groups. The median survival times for patients in Groups I, II, and III were 6, 7.5 and 11 months, respectively. The 2-year survival rates for patients in Groups I, II, and III were 0, 15.6%, and 34.3%, respectively. The prognosis in Group III was superior to that for Group I (P less than 0.05) and Group II. These results suggest that preoperative hyperthermia combined with radiotherapy and chemotherapy could prolong survival even in patients who have had noncurative resection.

Carcinoma↗

Serial histologic evaluation of multiple primary squamous cell carcinomas of the esophagus.

A review of data on 205 patients with esophageal squamous cell carcinoma who underwent subtotal esophagectomy revealed 30 cases (14.6%) and 32 lesions with multiple primary squamous cell carcinomas. The incidence of this multiplicity was 11.7% and 25.6% in those with and without preoperative irradiation treatment, respectively. Among the 32 second lesions, there were 17 intraepithelial carcinomas, eight restricted to the mucosa, five invading the submucosa, one invading down to the proper muscular layer, and one involving the entire thickness of the esophageal wall. These second lesions were in the relatively early stage. Moreover, incidence of the coexistence of intraepithelial carcinoma contiguous to the main lesion was 42.1% and 100.0% in those with multiple cancers, with and without preoperative irradiation, respectively. The values were 7.6% and 53.1% in patients with a solitary carcinoma, respectively. These findings show the close relationship between multiplicity and intraepithelial carcinoma contiguous to the main lesion, and support the concept of multicentric or field carcinogenesis of esophageal squamous cell carcinoma.

Adenocarcinoma↗

Multivariate approach for assessing the prognosis of clinical oesophageal carcinoma.

We investigated the prognostic contribution of 15 discrete variables on the survival of 123 patients with carcinoma of the oesophagus who underwent oesophagectomy and oesophageal reconstruction. In the multivariate analysis, three of fifteen variables were associated with the prognosis of patients who underwent oesophagectomy. The variables are: resectability of the malignant lesion, DNA distribution pattern of the cancer cells and postoperative complications. The DNA distribution pattern proved to be one of the most reliable prognostic factors. These three variables were assigned one of two values, 'favourable' or 'unfavourable', indicative of the effect on survival. The 123 patients were classified into four groups, characterized by eight possible combinations of these three variables. The survival rate of those with two or more 'favourable' variables was the highest, that is about 50 per cent at 5 years after surgery. On the other hand, patients with two or more 'unfavourable' variables had a very poor prognosis. Therefore, early detection and postoperative care play key roles in determining the survival of patients with oesophageal carcinoma.

Adult↗

Cytophotometric DNA analysis of esophageal dysplasia and carcinoma induced in rats by N-methyl-N-amylnitrosamine.

A series of esophageal lesions, mild, moderate and severe dysplasia, carcinoma in situ (CIS), early and advanced squamous cell carcinoma were induced in rats with N-methyl-N-amylnitrosamine (MAN). To evaluate the biological nature of each lesion, the ploidy level was estimated by microspectrophotometrical measurement of cell nuclear DNA content. DNA distribution patterns were classified into types I, II, III and IV, according to the degree of dispersion and the peak modal value on the DNA histogram. The incidences of type III of high ploidy in early cancer, CIS and severe dysplasia were 3/11 (27.3%), 5/13 (33.3%) and 4/16 (25%), respectively. On the other hand, in moderate and mild dysplasia, 15/16 (93.8%) and 20/21 (95.2%) were low ploidy (types I and II), respectively. The mean DNA content of advanced and early cancer, CIS and severe dysplasia were 3.88c, 3.34c, 3.24c and 3.13c, respectively, while those of moderate and mild dysplasia were near diploid, showing 2.67c and 2.51c, respectively. These findings indicate that the biological nature of severe dysplasia may be considered as serious a lesion as cancer, in terms of DNA analysis. Cytophotometric DNA analysis aids the evaluation of various degrees of dysplasia and carcinoma of the esophagus.

Animals↗

Lugol-combined endoscopic detection of minute malignant lesions of the thoracic esophagus.

Early-stage esophageal carcinomas, particularly cases of intraepithelial carcinoma and mucosal carcinoma, are extremely difficult to detect because the patients have no particular complaints, and findings on the x-rays are nil. At present, endoscopic examination is the only tool of any value for discerning such lesions. Lugol-combined endoscopy with biopsy has proven to be most effective for detecting the presence and spread of small malignant lesions of the esophagus. Studies were conducted on the diagnostic features of one intraepithelial, five mucosal and 29 submucosal carcinomas of the esophagus, detected through the use of Lugol-combined endoscopy.

Aged↗

Lethal effect of hyperthermochemoradiotherapy on cultured transformed cells.

Hyperthermia alone had a lethal effect on V-79 cells. Temporary exposure to hyperthermia resulted in substantial decreases in cell growth, in a time (20-120 min)- and temperature (39-44 degrees C)-dependent manner. A precipitous fall in cell growth occurred when cells were incubated at temperatures between 42 and 43 degrees C. Concomitant application of hyperthermia, bleomycin and irradiation (hyperthermochemoradiotherapy) led to a maximal effect, compared with findings in cells treated with a single or two modalities, in vitro as well as in vivo and in clinical cases. To produce a similar situation of tumor cell growth in vivo, multicellular tumor spheroids (MTS) were developed by culturing tumor cells on soft agar. The effect of various treatments on the cells was then determined. Hyperthermia had a greater effect on the inner layer (hypoxic state) of MTS than on the outer layer, while radiotherapy was more effective on the outer layer (aerobic state). The synergistic effect of the combination with hyperthermia and irradiation was exhibited in all layers of MTS. Hyperthermochemoradiotherapy may prove to be an effective and safe form of adjuvant therapy for treating clinical carcinoma.

Animals↗