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Biomedical subjects

H Kuwano

Publications and source records attributed to H Kuwano.

At least 199 records · Page 11Linked to original sources

Distribution of basement membrane antigens in human esophageal lesions: an immunohistochemical study.

The distribution of basement membrane components, type-IV collagen and laminin, was studied immunohistochemically in human samples of normal, hyperplastic, dysplastic and carcinomatous esophageal tissue. The expression of basement membrane components in normal, hyperplastic, and mildly and moderately dysplastic mucosa was characterized by a thick, continuous and linear staining pattern. In severe dysplasia and carcinoma in situ, the basement membrane was thinner and occasionally discontinuous. The distribution of basement membrane in invasive carcinomas varied greatly; well-differentiated, cohesive tumors had a basement membrane, however, poorly-differentiated tumors showing irregular cords, or individual cell infiltration, lacked this membrane at the tumor-stromal interface. Many moderately-differentiated tumors showed probable immature assembly of basement membrane components. The expression of basement membrane was also influenced by the extent of stromal inflammation. The absence or presence (staining pattern) of basement membrane components in esophageal squamous-cell carcinoma did not correlate with the survival rate, but did correlate with the histologic differentiation of epithelial organization.

Adult↗

Predicting recurrence time of esophageal carcinoma through assessment of histologic factors and DNA ploidy.

Cytophotometric analysis of nuclear DNA content was done in 128 patients with squamous cell carcinoma of the esophagus. The relationship among histopathologic features, DNA distribution pattern, and survival time was investigated from the standpoint of recurrence. Of 128 patients, 77 (60.1%) died of recurrence within 2 years after surgery: 16 (12.5%) from 2 to 5 years and two (1.6%) over 5 years. The rate of death of recurrence within 2 years was higher in patients with T4 or N1 than T1, T2, and T3 or N0 (P less than 0.01). Survivors over 5 years more frequently possessed type II DNA pattern than types III and IV (P less than 0.05). The rate of death of recurrence within 2 years was 34.4% in type II, which was lower than the 59.6% rate in type III (P less than 0.05) and the 76.6% rate in type IV (P less than 0.01). Survivors from 2 to 5 years were higher in type III than in type IV (P less than 0.05), and recurrence over 5 years was found only in type II. This inclination was more apparent in those with curative resection. In the patients with type II, careful follow-up may be needed over 5 years for late recurrence. However, in those with type IV, no recurrence over 2 years could be regarded as healed because most of their recurrences occur within 2 years. These findings suggest that the growth rate of esophageal carcinoma should reflect DNA aneuploidy, and the DNA analysis of esophageal carcinoma should be a valuable parameter for postoperative follow-up planning.

Carcinoma, Squamous Cell↗

Surgical resection of pulmonary metastases from colorectal adenocarcinoma. Special reference to repeated pulmonary resections.

Pulmonary resection of metastatic lesions from colorectal adenocarcinoma was performed in 35 patients. The cumulative 5-year survival was 38%. The primary site of cancer was the colon in about half of the patients. Patients with a solitary metastasis or tumors smaller than 3 cm in diameter survived longer than did patients with multiple metastases or tumors larger than 3 cm but the differences were not significant. Other factors, including age, sex, histologic grade of tumor, location and stage of primary carcinoma, location of pulmonary metastases, disease-free interval, and type of pulmonary resection, had no apparent influence on survival time. The lung was the major site of recurrence following pulmonary resection. Seven patients underwent two or more pulmonary resections for metastasis from a colorectal carcinoma. At the time of last follow-up, four patients were alive and free of recurrent disease at 5, 34, 39, and 58 months after the second pulmonary resection. These data suggest that some patients will survive for a long time following pulmonary resection of colorectal metastases, and for highly selected patients, repeated pulmonary resection may further extend survival.

Adenocarcinoma↗

Comparison of characteristics of esophageal squamous cell carcinoma associated with head and neck cancer and those with gastric cancer.

In ongoing reviews of 339 patients with surgically treated primary squamous cell carcinoma, there were 19 (5.6%) with concurrent gastric cancer and 11 (3.2%) with head and neck cancer. The incidences of intra-esophageal multiple occurrence of esophageal cancer are 27.3% and 26.3% in those with associated head and neck cancer and gastric cancer, respectively, and higher than 7.1% in those without such a concurrent cancer. There was no difference in the clinicopathological characteristics of those with concurrent head and neck and gastric cancers, except for the higher incidence of metachronous occurrence in the former. These findings suggest that, in cases of esophageal cancer associated with concurrent head and neck cancer and gastric cancer, intraesophageal multiplicity of the esophageal carcinoma is frequent and that preoperative serial evaluations is most important to design treatment and estimate the prognosis.

Aged↗

Lugol stain for intraoperative determination of the proximal surgical margin of the esophagus.

An adequate proximal surgical margin is difficult to determine particularly in cases of esophageal carcinoma with surrounding intraepithelial invasion. We report here readily facilitated intraoperative approaches for detection of the exact margin of carcinomatous invasion of the esophagus. The resected specimen of the esophagus is incised longitudinally and placed in a 1% Lugol bath for 2-3 minutes. The normal squamous epithelium includes glycogen that interacts with the iodine of Lugol's solution and the normal epithelium of the esophagus becomes a uniform greenish-brown. A squamous cell carcinoma does not include glycogen, hence is not stained with this solution and a clear identification is feasible. Thus, a carcinomatous infiltration not recognizable in routine examinations becomes macroscopically visible when Lugol's solution is used.

Adult↗

Ten-year survivors after surgical treatment and perioperative irradiation for esophageal carcinoma.

Ten of 150 patients with primary squamous cell carcinoma of the esophagus and surgically treated, survived for more than 10 years. All 10 underwent a complete resection of the primary tumor and extensive lymph node dissection plus perioperative irradiation. The clinicopathologic findings in these 10 patients were reviewed. Five were female. Seven of the tumors exceeded 6 cm in length; seven were early stage, and the remaining three were advanced stage tumors. Lymph node metastases were evident in three, lymph vessel permeation was recognized in four, and no vascular vessel permeation was seen in any tumor. Two tumors had a characteristic appearance of carcinoma with lymphoid stroma, suggesting a good prognosis. In six for which cytophotometric DNA analysis could be done, four were type II, two were type III, and none was type IV. Thus, a complete resection of the primary tumor and extensive lymph node dissection can lead to a long survival time even for those with an advanced primary esophageal carcinoma.

Aged↗

Increased cytotoxicity of low-dose, long-duration exposure to 5-fluorouracil of V-79 cells with hyperthermia.

We examined the cytotoxic effects of combined low dose and long exposure to 5-fluorouracil (5-FU) and hyperthermia on Chinese hamster V-79 cells with reference to timing and sequence of administration. The survival rate following hyperthermia at 42 degrees C for 2 h alone was 95.4%, and that after exposure to 1.0 micrograms/ml/5-FU alone for 48 hours, 94.2%. With respect to the combination of 5-FU and heat, the survival rate of cells exposed to hyperthermia at 42 degrees C for 2 h followed by 1.0 micrograms/ml 5-FU treatment for 48 h followed by hyperthermia led to a survival rate of 10%. Flow cytometric analysis of V-79 cells after exposure to 1.0 micrograms/ml 5-FU for 48 h revealed an accumulation of cells in the S-phase; the percentage of S-phase exponential growing cells was 65% and the plateau phase was 38%. The former were more sensitive to heat than the latter cells according to the MTT assay. V-79 cells pretreated with 5-FU were more sensitive to hyperthermia than were those not pretreated with 5-FU. Therefore, when 5-FU plus heat is to be used to treat a patient with a malignancy, the sequence of 5-FU followed by hyperthermia may be more effective than the reverse.

Animals↗

Comparison of cell nuclear DNA contents between intraepithelial and invasive components of oesophageal squamous cell carcinoma.

Detailed cytophotometric analyses of cell nuclear DNA content were performed on 132 different areas from 24 oesophageal squamous cell carcinomas with an intraepithelial component. Measurements of DNA content were performed at the three different areas within each of the intraepithelial and invasive components. There were no differences in the overall incidence of DNA distribution patterns which were classified according to the degree of dispersion and the peak value on the DNA histogram between intraepithelial and invasive components, as well as the average of mean values of the DNA content. In 13 (54%) of 24 cases, there was a variation among the DNA distribution patterns obtained from three different areas of the intraepithelial components, whereas there was a variation in 4 (22%) of the 18 invasive components. In 11 of 13 intraepithelial components with a variation, the same DNA distribution pattern as seen in the invasive component was present. Provided that the DNA content remains stable, variations in intraepithelial components may reflect various tumour cell populations. These findings support the idea of a multicentric carcinogenesis of oesophageal carcinoma, and shed light on the mechanisms in which a single cell population is selected from various cell populations in the progression from an intraepithelial to an invasive lesion.

Carcinoma in Situ↗

Metabolism of pravastatin sodium in isolated rat hepatocytes. II. Structure elucidation of the metabolites by n.m.r. spectroscopy.

1. The structures, including stereochemistry, of the two major metabolites of pravastatin sodium in an isolated rat hepatocyte system, i.e. the 4'a alpha-glutathione conjugate (CM-1) and the 3',5'-dihydrodiol (CM-2), were determined by one- and two-dimensional n.m.r. spectroscopy. 2. The structures of two synthetic pravastatin epoxides, possible precursors of the metabolites, were also established. 3. One of the synthetic epoxides, 4'a beta, 5' beta-epoxide was converted to the pravastatin metabolite, 4'a alpha-glutathione conjugate (CM-1) by a rat liver cytosol system and is proposed as the common metabolic intermediate between pravastatin sodium and the metabolites, CM-1 and CM-2.

Animals↗

Proposed new criteria for early carcinoma of the esophagus.

The criteria of early carcinoma of the stomach, defined in 1981, has gained worldwide acceptance. A few proposals of a criteria for early carcinoma of the esophagus have been made; however, these criteria have not been internationally accepted, as the rate of recurrence is high in patients with early carcinoma of the esophagus, as determined by these criteria. In patients with submucosal carcinoma of the esophagus, metastasis to lymph nodes was present in 32.5 per cent at the time of the operation, and the five year survival rate was only 54.5 per cent. On the other hand, while the incidence of epithelial or mucosal carcinoma, or both, is only 2.2 per cent (46 of 2,130) in patients with carcinoma of the esophagus, the incidence has been remarkably increased and the five year cumulative survival rate for patients with epithelial carcinoma or mucosal carcinoma, or both, is now 88.4 per cent. Thus, we consider that the criteria for early carcinoma of the esophagus to be mucosal carcinoma as well as epithelial carcinoma regardless of the presence or absence of lymph node metastasis, and that a submucosal carcinoma should be excluded from the classification of early carcinoma of the esophagus.

Esophageal Neoplasms↗

[A consideration of the definition of early esophageal cancer on the basis of clinicopathologic viewpoint].

A review of 323 patients with carcinoma of the esophagus disclosed 50 cases (15.5%) with glandular and/or mucus-secreting components, in addition to the ordinary component of squamous cell carcinoma. These tumors could be grouped into three type according to representative histologic features of glandular and mucus-secreting portions: glandular type (28 cases), cribiform type (14 cases), and mucoepidermoid type (8 cases). The histologic features of the three types were reminiscent of those of adenocarcinoma, adenoid cystic carcinoma, and mucoepidermoid carcinoma of salivary glands, respectively. Moreover, areas showing glandular or mucus-secreting differentiation were in greater part located in the submucosa and the lamina propria mucosae, thereby suggesting that such differentiation had arisen in the esophageal glands or their ducts. From these findings, in addition to intraepithelial and mucosal carcinomas, carcinoma restricted to the submucosal layer without lymph node metastases should be also defined as "early" esophageal cancer and definition of it according to the existing Guide Lines for the Clinical and Pathologic Studies on Carcinoma of the Esophagus is thought to be adequate at present.

Adenocarcinoma↗

Inhibitory effects of estrogen on the growth of a human esophageal carcinoma cell line.

In order to accurately determine sex hormone dependency and hormone responsiveness in human esophageal carcinoma, the effects of sex hormones on the growth of esophageal carcinoma cell lines, KSE-1 and KSE-2 cells, were examined in vitro and in vivo. Cell proliferation of cultured KSE-1 cells was inhibited by treatment of estradiol and enhanced by dihydrotestosterone (DHT), whereas KSE-2 cells were unaffected by these sex hormones. The heterotransplanted tumors of KSE-1 cells in nude mice possessed estrogen receptor (ER) and androgen receptor (AR), while the tumors of the KSE-2 cells had neither ER nor AR. When the tumor growth rates and serum hormone levels were monitored during the continuous administration of either estradiol or DHT, no significant differences were observed in either the serum hormone levels or tumor growth rates between male and female mice. The administration of estradiol significantly inhibited the growth of ER-positive and AR-positive KSE-1 tumors in both males and females in conjunction with an increase in the estradiol levels and a decrease in the DHT levels in the serum. However, the growth of ER-negative and AR-negative KSE-2 tumors was not influenced by either estradiol or DHT administration. These results suggest that the in vivo growth of human esophageal carcinoma cells with sex hormone receptor is influenced by circulating hormone levels and can be manipulated by systemic estradiol administration.

Animals↗

Confluent BALB/c 3T3 cells monolayer provides selective and efficient growth of neoplastic cells.

In an attempt to further characterize non-irradiated contact-inhibited confluent monolayer of BALB/c 3T3 cells (= Contact-Sensitive Plates; CSP) as substrata for in vitro drug sensitivity testing, we compared the efficiency of colony formation with panels of cell lines on CSP with that on plastic dishes or in agar. Tumorigenicity in athymic nude mice was also examined. We found that: (1) HeLa cells, 2 esophageal cancer lines, rat 3Y1 fibroblasts transformed by either adenovirus type 12, mouse polyoma virus, Rous avian sarcoma virus, or plasmid DNA carrying v-Ha-ras oncogene all formed colonies on CSP and in agar and at the same time was tumorigenic. The efficiency of colony formation on CSP proved always to be higher than that in agar. (2) None of the 4 "normal" fibroplastic cell lines formed colonies on CSP or in agar and were tumorigenic. (3) Simian virus 40 and adenovirus E1A gene transformed rat 3Y1 fibroblasts formed colonies on CSP but not in agar, and were not tumorigenic. Therefore, CSP was found to provide selective and efficient growth of neoplastic cells when compared to other substrata and is also helpful in detecting incompletely transformed cells.

Animals↗

Immunohistochemical evaluation of squamous cell carcinoma antigen and S-100 protein-positive cells in human malignant esophageal tissues.

Localization and intensity of squamous cell carcinoma-related antigen (SCC-Ag) and infiltration of Langerhans' cells (LC) were investigated immunohistochemically, using anti-SCC-Ag and anti-S-100 protein antisera, respectively, in 36 cases of squamous cell carcinoma of the human esophagus. The SCC-Ag was an indicator of histologic differentiation of squamous cell carcinoma but not of malignant potential. The population density of LC correlated well with the histologic stage, vessel invasion, and postoperative survival time. In patients with a marked infiltration of LC, survival time was longer than for those in whom the infiltration was slight (P less than 0.05). The density of the LC can serve an indicator of defense of the host against the carcinoma. There was no correlation between SCC-Ag and S-100 protein-positive cells.

Adult↗

Safety of EEA staplers for anastomosis between upper esophagus and the gastric tube.

The EEA stapling devices used for intrathoracic anastomosis between the upper esophagus and the gastric tube in patients with carcinoma of the thoracic esophagus were evaluated, and the results were compared with those of an antesternally reconstructed esophagus. These approaches were both used by the same surgical team. An intrathoracic anastomosis using the EEA stapler was made in 53 patients with carcinoma of the thoracic esophagus. Minor anastomotic leakage occurred in five patients (9.4%). Good results were obtained with total parenteral nutrition for 2 weeks. Intrathoracic anastomotic complications were never fatal. Among another 106 patients with antesternally reconstructed esophagus, with the EEA stapler there were 28 patients with anastomotic leakage (26.4%) and two operative mortalities (1.9%). Intrathoracic anastomosis with the EEA stapler is recommended because it is secure and the operative procedure is simple and time-saving. For successful use of the instrument, proper technical procedures must be followed.

Adult↗

Clinicopathological features of elevated lesions of the duodenal bulb.

We present here our findings on patients with an elevated lesion of the duodenal bulb. All these patients were treated in our clinics between the years 1984 and 1988. These lesions were present in 36 of 8,802 patients who underwent upper gastrointestinal pan-endoscopy. Two patients had a duodenal carcinoma, 2 an adenoma, and 1 a Brunner's gland adenoma. There were 15 with a hyperplastic polyp, 3 with a heterogenic gastric mucosa, 3 with Brunner's gland hyperplasia, 6 with duodenitis, and 4 with regenerative mucosa. Among these 36 lesions, only 69% (25 lesions) were evident on the upper gastrointestinal X-ray series. Adenoma and Brunner's gland adenoma were of a pedunculated form of the gross type and had an irregular surface mucosa. Both duodenal carcinomas were detected by endoscopic biopsy and were resected. Histologically, these lesions were limited to the submucosal layer and were of the non-pedunculated polypoid form, but there were no other characteristic endoscopic features, in comparison with other elevated lesions. Thus, upper gastrointestinal endoscopy with routine observations of the duodenal bulb plus endoscopic biopsy will lead to a definite diagnosis of these elevated lesions and to the early detection and treatment of this rare malignant lesion.

Adenocarcinoma↗