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Biomedical subjects

H Kuwano

Publications and source records attributed to H Kuwano.

At least 217 records · Page 12Linked to original sources

DNA analysis and prognosis of digestive tract cancers.

Cytophotometric DNA analysis was performed on esophageal and gastric carcinomas. In 35 cases of mucosal and submucosal carcinoma of the esophagus, patients with types I and II (relatively regular in DNA distribution) had an uneventful postoperative course and no recurrence, whereas 3 of 15 (20%), and 5 of 9 (55.6%) with type III and type IV, respectively (widely scattered DNA distribution, died following a recurrence. Cytophotometric DNA analysis using biopsy specimens from 75 patients with esophageal cancer in various stages also showed a close relationship between the DNA distribution pattern and prognosis. However, the growth mode and the DNA ploidy of mucosal gastric cancer correlated well in the investigation of 66 cases. Thus, data of this method closely reflected the outcome in patients with digestive tract cancers. These results suggested the potential usefulness of cytophotometric DNA analysis for assessing the prognosis, even in the early stage of cancers.

Adult↗

Transitional mucosa in human colorectal lesions.

Mucosa adjacent to colorectal disease was studied mucin-histochemically. Selected specimens were also studied immunohistochemically for carcinoembryonic antigen (CEA). Transitional mucosa, which showed elongation of crypts and marked sialomucin secretion, accompanied by a marked reduction in the normal sulfomucin content, was evident in 96 of 100 carcinomas (96 percent), 18 of 36 adenomas (50 percent), and 10 of 30 metaplastic polyps (33 percent). When considering the appearance of transitional mucosa, not only in the neoplastic lesions such as carcinoma or adenoma but also in the begin polyp, the transitional change adjacent to the carcinoma cannot be classified as a precancerous phenomenon; rather, it is a secondary one. The mucin-histochemical study disclosed transitional mucosa in all the 21 carcinomas less than 1 cm in diameter and immunohistochemical staining for CEA showed no remarkable change in the adjacent mucosa. Thus, it seems apparent that a change in mucous secretion precedes that of CEA expression in the mucosa adjacent to the carcinoma.

Adenocarcinoma↗

Sensitivity to heat and radiation of human rectal malignant tissues in vitro.

The sensitivity to heat and radiation of 22 rectal cancer tissues obtained at biopsy was studied using the in vitro succinate dehydrogenase inhibition test. The succinate dehydrogenase activity of tissue fragments was assayed after exposure at 43 degrees C (hyperthermia) for 20 hours, to radiation of 6 Gy, and to both heat (43 degrees C) and radiation (6 Gy). The sensitivity to each treatment was estimated by the percentage of succinate dehydrogenase activity of the treated cells compared with that of control cells. The mean plus or minus standard deviation of succinate dehydrogenase activity after exposure to radiation, heat, and both heat and radiation, was 84.7 +/- 12.6 percent, 52.9 +/- 20.7 percent, and 46.8 +/- 20.7 percent, respectively. The succinate dehydrogenase activities of heat-treated cells and both heat- and radiation-treated cells were significantly lower than that of the radiation-treated cells (P less than 0.01). The succinate dehydrogenase activities of heat plus radiation treated cells were the lowest in tissues from cancer lesions. Although the number was small, there was a correlation between this test and clinical outcome in seven of nine cases. Thus, preoperative therapy of hyperthermia plus radiotherapy is expected to be effective for treating patients with rectal cancer.

Cell Survival↗

Esophageal carcinoma in young patients.

The clinicopathological features of esophageal carcinoma were examined from the viewpoint of age differences in a study of 364 consecutively treated patients. The three groups studied were: group I, aged less than 49 years; group II, aged between 50 and 69 years; and group III, aged more than 70 years. There were no significant differences among the three groups with regard to sex ratio, site and length of the lesion, gross types, histological grade, depth of tumor invasion, vessel permeation, lymph node metastasis, TNM classification, incidence of incomplete resection, or crude actuarial 5-year survival curves. The malignant potentiality of the esophageal carcinoma in young patients did not differ from that in older patients in terms of deoxyribonucleic acid distribution pattern. The only difference clearly evident between young and older patients was the number of hospital deaths due to complications: That of the young patients was significantly lower than that of the older patients (p less than 0.05). Esophageal carcinoma in persons aged less than 50 years appeared to behave biologically like the same neoplasm in older people, whereas gastric and colorectal carcinomas behave differently in various age groups.

Adult↗

Endoscopic ultrasonographic detection of carcinomatous invasion and of lymph nodes in the thoracic esophagus.

The use of endoscopic ultrasonography (EUS) for diagnosing the depth of carcinomatous invasion into the esophageal wall and in detecting mediastinal lymph nodes in patients with esophageal carcinoma was assessed. EUS was performed before surgery in 33 patients who underwent subtotal esophagectomy with lymph node dissection in our department of surgery between January 1987 and February 1989. The findings of EUS prospectively correlated with intraoperative macroscopic findings and histopathologic findings of the resected specimens. An accurate diagnosis of the depth of invasion into the esophageal wall was made in 30 of the 33 patients (90.1%). Visualization rates of mediastinal lymph nodes were 92.9%, 53.1%, and 1.0% when the nodes were greater than 10 mm in maximum diameter, 5 to 9 mm, and less than 5 mm, respectively. Although EUS had no diagnostic value for patients in whom the ultrasonic probe could not be inserted beyond the tumor, it is an excellent method for evaluating the depth of invasion and detecting lymph nodes greater than 10 mm in diameter. Detection is not feasible when the lymph node is less than 5 mm in diameter. EUS provides the surgeon with one more tool for the preoperative determination of curability.

Adult↗

Correlation between hyperthermoradiosensitivity and clinical effect in carcinoma of the esophagus.

The correlation between hyperthermoradiosensitivity evaluated by an in vitro succinate dehydrogenase inhibition (SDI) test and the histopathologic effects of hyperthermochemoradiotherapy (HCR therapy) were investigated in 43 patients with carcinoma of the esophagus. The succinate dehydrogenase (SD) activity of tissue fragments taken at biopsy was assayed after exposure to heat (43 degrees C.) and radiation (6 grays) was done. The sensitivity to radiation plus heat treatment was estimated by the percentage of SD activity of the treated cells, compared with that of the control cells. The 43 patients were divided into three groups according to the degree of SD activity after exposure to radiation plus heat treatment. The SD activity was less than 50 per cent in group 1 (highly sensitive), between 50 and 70 per cent in group 2 (moderately sensitive), more than 70 per cent in group 3 (less sensitive). Eighteen of 20 in group 1, 11 of 17 in group 2 and two of six in group 3 were classified as being histopathologically "effective" for HCR therapy. The two year survival rate for groups 1, 2 and 3 were 55.5, 34.9 and zero per cent, respectively, while there were no statistical differences with regard to prognostic factors. These data suggest that in vitro activities of SD correlate well with the clinical effectiveness of HCR therapy. Therefore, it is recommended that a SD inhibition test be included among the guidelines for clinical management.

Adult↗

DNA aneuploidy assessment of the effectiveness of hyperthermo-chemo-radiotherapy for esophageal carcinoma.

The relationship between DNA ploidy and effects of preoperative hyperthermo-chemo-radiotherapy were investigated in 118 patients who underwent esophageal resection and reconstruction for carcinoma of the esophagus, including 56 treated with hyperthermo-chemo-radiotherapy (HCR therapy) and 62 treated with chemo-radiotherapy (CR therapy). DNA ploidy patterns were grouped into low and high ploidies, according to the degree of dispersion and the peak value on the DNA histogram. In the low ploidy group, there were no significant differences in the prognosis and histologic effects between the HCR and CR therapies. In the high ploidy group, however, the difference in survival curves was statistically significant, the 3-year survival rates of patients given HCR therapy and CR therapy being 26.7% and 10.7%, respectively (P less than 0.05). The HCR therapy increased the rate of "markedly effective" in the resected tissue compared with findings in cases of CR therapy. These findings show the positive effects of the HCR therapy for carcinoma of the esophagus, especially for patients with an aneuploid profile and a poor prognosis.

Aged↗

Hyperthermia, tissue microcirculation, and temporarily increased thermosensitivity in VX2 carcinoma in rabbit liver.

The role of microcirculatory factors within and around liver tumors after heat treatment was investigated in a rabbit model of liver cancer (VX2 carcinoma). As a physiological factor of the microenvironment, regional blood flow (RBF) was measured by the hydrogen clearance method, and a histopathological study was done. Local hyperthermia was administered directly to the liver tumor via a 915-MHz microwave. Hyperthermia produced a temporary reduction of RBF in both the tumor and the surrounding normal liver tissues, and the histopathology revealed congestion, petechiae, and thrombosis. After hyperthermia at 43.0 degrees C for 20 min, RBF in the tumor rapidly decreased to a minimum of 40% of the control level during 0-12 h after the treatment and increased gradually to the pretreatment level at 2 days. RBF in the normal liver also decreased rapidly after hyperthermia, to a minimum of 30% of the pretreatment level, 1-12 h after treatment. In the case of treatment at 42.5 degrees C for 20 min, RBF in the tumor also rapidly decreased to a minimum of 40% of the control level, at 4 h after the treatment, and recovery was within 2 days. However, RBF in the surrounding normal liver decreased to 80% of the control level, at 2 h after the treatment, and then increased more rapidly to reach levels seen in the controls. Thus, the latter condition of heat treatment was considered to be favorable for therapeutic gain. Based on the results of these sequential microcirculatory changes, the effects of continuous and intermittent hyperthermia were studied in groups given various treatments. In a group treated with intermittent hyperthermia at 4-h intervals, the antitumor effects determined by tumor growth retardation were significantly greater, as compared with findings in the group given treatment without an interval and that given at a 24-h interval (P less than 0.001). In the tumor at 4 h after hyperthermia, the increased thermosensitivity was considered to surpass the developing thermotolerance. Thus, the antitumor effect of hyperthermia in vivo greatly depends on the microcirculation. The most efficacious mode for application of hyperthermia must be vigorously examined if a clinical relevance is to be gained.

Animals↗

Small cell carcinoma of the esophagus.

Ten cases of small cell carcinoma of the esophagus were studied clinicopathologically and immunohistochemically. Seven of the ten were also examined by electron microscopy. Histologically, six were oat cell type, four the intermediate cell type, and multiple histologic sections revealed squamous and glandular differentiations in small or minute areas of seven and two tumors, respectively. In four of the six polypoid tumors, the epithelium covering the tumor showed a malignant conversion accompanied by a proliferation of small anaplastic cells. Another one showed a cribriform pattern in a small area of the tumor. Argyrophilic tumor cells were seen in six cases and tumor cells immunohistochemically positive for ACTH and calcitonin were seen in six, and three cases, respectively. Neurosecretory granules were evident in three of the seven cases examined by electron microscopy. These findings suggest that a small cell carcinoma of the esophagus differentiates toward a squamous, glandular, or neurosecretory lesion, thereby supporting the idea of a totipotential stem cell origin of this tumor. The prognosis of patients with this tumor was poor, in accord with the evidence of aggressive lymphatic and blood vessel permeation.

Adult↗

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.

Adenocarcinoma↗

Occurrence of esophageal carcinoma after gastrectomy.

A review of data on 548 patients with primary squamous cell carcinoma revealed that 24 (4.4%) had had gastrectomy. Although the interval of the gastrectomy due to peptic ulcer or gastric cancer and esophageal cancer was 13.4 +/- 7.9 and 5.8 +/- 4.2 years, respectively, this difference was thought to be due only to the occurrence of each disease. The incidence of the occurrence of the lower esophageal cancer after gastrectomy was 29.2%, not significantly higher than the 22.4% incidence of lower esophageal cancer in overall cases. Histopathological investigation of the 13 resected esophageal cancer tissues from gastrectomized patients revealed a mild esophagitis in some cases, with no significant histologic characteristics. Thus esophageal squamous cell carcinoma and previous gastrectomy may be incidentally related.

Aged↗

Hypercalcemia related to the poor prognosis of patients with squamous cell carcinoma of the esophagus.

A review of 208 cases of surgically treated squamous cell carcinoma of the esophagus revealed 16 (7.7%) with hypercalcemia. There was no evidence of bone metastases in 13 (6.3%) of the patients with hypercalcemia. Pathogenesis of this hypercalcemia without bone metastases was suggested to be multifactorial. Anastomotic leakage and malnutrition because of fasting were the most possible causes of mild hypercalcemia, and moderate to severe hypercalcemia was thought to be due to subclinical and clinical recurrence of the tumor, probably with PTH-like hormonal activity. Overall survival rates in the groups with and without hypercalcemia were 18.2 and 61.7% at the 12th postoperative month and 9.1 and 37.8% at the 24th month, respectively. Thus hypercalcemia is a significant prognostic factor linked to an unfavorable clinical course even in patients with no evidence of bone metastases.

Bone Neoplasms↗

Oesophageal squamous cell carcinoma with lymphoid stroma. A case report.

We treated a 70-year-old Japanese man with squamous cell carcinoma of the oesophagus with evidence of lymphoid stroma. The tumour consisted of a main lesion invading the muscular layer of the oesophagus, in association with wide areas of carcinoma in situ. The tumour stroma of the lesion was nondesmoplastic and was uniformly infiltrated mainly by abundant lymphocytes and plasma cells. Immunohistochemically, the lymphocytes consisted of a large number of T lymphocytes and a small number of B lymphocytes. S-100 protein positive cells were marked in the tumour cell nests and necrotic change of tumour cells was frequent. Abundant infiltration of lymphocytes and plasma cells was also wide-spread beneath the carcinoma in situ, together with the lymphoid follicles. Carcinoma with lymphoid stroma can occur not only in the breast, uterine cervix, nasopharynx and stomach but also in the oesophagus.

Aged↗

Preoperative hyperthermochemoradiotherapy for patients with rectal cancer.

Preoperative hyperthermochemoradiotherapy (HCR therapy), consists of a combination of hyperthermia at 42 to 45 degrees C for 40 minutes (2 times per week for two weeks), 5-fluorouracil (5-FU) intravenously (total, 1000 to 1750 mg), and a total of 30 Gy irradiation. The therapy was prescribed preoperatively most recently for 11 patients with rectal cancer. The authors used a radiofrequency system involving an endotract electrode with thermosensors for the hyperthermia. The effectiveness of preoperative HCR therapy was evaluated by irrigography, fiberscopy, and histopathologic findings in the resected specimens. Reduction in tumor size and amount was evident in all patients, with all modes of assessment. Histologically, no or only a few viable cancer cells were seen in the resected specimens in six patients, a small number of viable cancer cells in three, and a fair number of viable cancer cells in two patients; there were no complications. This method of treatment is expected to play an important role in the interdisciplinary treatment for rectal cancer.

Adult↗

Lack of muscularis mucosa and the occurrence of Boerhaave's syndrome.

Six patients with spontaneous rupture of the esophagus (Boerhaave's syndrome) were surgically treated in the Department of Surgery II, Kyushu University. Two patients underwent esophageal resection. Histopathologic examinations revealed the absence of muscularis mucosa around the sites of esophageal rupture in these two patients. In the patient treated most recently, serial histologic investigation demonstrated that the lack of muscularis mucosa existed not only around but also along the longitudinal extension of the site of rupture. This finding suggests that lack of muscularis mucosa in the esophageal wall may be one cause of spontaneous rupture of the esophagus.

Adult↗

Solitary Peutz-Jeghers type polyp of the stomach in the absence of familial polyposis coli in a teenage boy.

We treated a male teenager with a solitary gastric Peutz-Jeghers type (hamartomatous) polyp showing neither mucocutaneous pigmentation nor inheritance. X-ray studies of the upper gastro-intestinal tract, small intestine and barium enema revealed a solitary thumb tip-sized polypoid mass in the posterior wall of the gastric body, with no evidence of any associated lesion. Histologically, the polypoid mass showed typical features of a Peutz-Jeghers type (hamartomatous) polyp. This may be the first documentation of a "solitary" gastric Peutz-Jeghers type polyp, in the absence of familial polyposis coli and mucocutaneous pigmentation.

Adenomatous Polyposis Coli↗

Effects of hyperthermochemoradiotherapy on KSE-1 cells, a newly established human squamous cell line derived from esophageal carcinoma.

Hyperthermia alone inhibits growth of the human esophageal cancer cell line (KSE-1). Even temporary exposure to hyperthermia results in substantial decreases in growth in a time- and temperature-dependent manner. A precipitous decrease in growth occurred at a temperature of approximately 42.5 degrees C. Concomitant application of hyperthermia, bleomycin and irradiation (hyperthermochemoradiotherapy, HCR) had a maximal effect on cell growth, compared to findings in cells treated with only one or two of these modalities. Fractionated hyperthermia (42 degrees C, 60 min) at a time interval of under 12 h was less effective than a single application (42 degrees C, 120 min). However, over a 12-hour time interval, the effects of both treatments were similar. Fractionated HCR (hyperthermia: 42 degrees C, 60 min; chemotherapy: 2 micrograms/ml of bleomycin, 60 min; radiotherapy: 2 Gy) at a time interval of under 21 h was less effective than a single HCR (hyperthermia: 42 degrees C, 120 min; chemotherapy: 2 micrograms/ml of bleomycin, 120 min; radiotherapy: 4 Gy). We conclude that care should be taken regarding development of thermotolerance when combined modality therapy is given.

Animals↗

Mureidomycins A-D, novel peptidylnucleoside antibiotics with spheroplast forming activity. II. Structural elucidation.

Structures of new antibiotics, mureidomycins (MRD's) A approximately D, were deduced from spectroscopic analyses and degradation studies. Two residues of m-tyrosine, one residue of 2-amino-3-N-methylaminobutyric acid (AMBA) and methionine are present in all components of the complex. Uracil is contained in MRD's A and C, while dihydrouracil in MRD's B and D. Methionine and m-tyrosine are connected through an ureido bond, and uracil or dihydrouracil is linked to AMBA via enamine sugar moiety. In addition, MRD's C and D contain a glycine residue at the N-terminal.

Amino Acids↗