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Biomedical subjects

H Kuwano

Publications and source records attributed to H Kuwano.

At least 307 records · Page 17Linked to original sources

Operative procedures of reconstruction after resection of esophageal cancer and the postoperative quality of life.

To investigate the influence of the operative procedures of reconstruction after resection of esophageal cancer on the postoperative quality of life, an interview was conducted and subjective and objective factors related to the quality of life were evaluated in 50 patients without a recurrence of esophageal cancer. Among the 50 cases, reconstruction by the antethoracal route was performed in 9 (group I) and by the retrosternal route in 24 (group II). Intrathoracic anastomosis was done in 17 (group III). A postoperative disturbance of the food passage was seen 22.0, 41.6, and 5.9% in groups I, II, and III, respectively. Dumping symptom was evident 11.1, 12.5, and 11.8%, respectively. Heartburn was seen only in two cases, in group III. A body weight loss of more than 1.0 kg from preoperative weight was seen in 33.3, 41.7, and 41.2% of groups I, II, and III, respectively. There was no difference in the postoperative performance status or laboratory data among the groups. Thus, although intrathoracic anastomosis was favorable for postoperative food passage, there was no significant difference in any other factors in the quality of life among the routes of reconstruction, and the quality of life gradually improved in patients of all groups as postoperative time passed in the cases without postoperative recurrence of esophageal cancer.

Esophageal Neoplasms↗

Endoscopic diagnosis of early carcinoma of the esophagus using Lugol's solution.

Small esophageal lesions, particularly intraepithelial cancers, are extremely difficult to detect. We used Lugol's iodine solution with panendoscopic examination to detect the presence and spread of small squamous cell carcinomas of the esophagus. Serial histologic specimens of the surgically removed esophagus from 32 patients with Lugol's combined endoscopic diagnosis of early esophageal carcinoma were examined to determine the correlation between endoscopic and histologic findings. All of the early staged carcinomas clearly remained unstained by Lugol's solution. We believe that the application of Lugol's solution will greatly aid in instances when a suspicious mucosal lesion is noted, when the margin of the lesion is unclear, or when there is suspicion that a mucosal lesion may have been overlooked.

Aged↗

DNase I is present in the chief cells of human and rat stomachs.

The distribution of deoxyribonuclease I (DNase I) in human and rat stomachs was examined by biochemical, molecular biological and immunohistochemical techniques. By the use of monoclonal anti-human DNase I and polyclonal anti-rat DNase I antibodies, we determined that strong immunoreactivity was present in the cytoplasm of chief cells of the human fundus and the rat pars glandularis, respectively. High DNase I enzyme activity was detected in tissue homogenates of both human fundus and rat pars glandularis. The presence of DNase I-specific mRNA was verified by reverse transcriptase-polymerase chain reaction analysis of the total RNAs extracted from human and rat stomachs. Immunoelectron microscopy revealed gold particles localized in the chief cells, with most labelling in exocrine secretory granules. These results show that the chief cells of human and rat stomach produce DNase I. This is the first report to demonstrate that secretion of DNase I is controlled by the chief cells in human and rat stomachs.

Adult↗

Mechanism of hyporesponsiveness caused by donor-specific transfusion to allogeneic minor antigens.

Donor-specific transfusion (DST) is one of the methods to prevent allograft rejection, presumably through induction of donor-specific nonresponsiveness in humans and animal models. In this study, we used a skin graft model in fully allogeneic (AKR into B6), H-2 class I-disparate (bm1 into B6), class II-disparate (bm12 into B6), minor-H-disparate (C3H/SW into B6) and whole MHC-disparate (B10.BR into B10) combinations to analyze the mechanisms of DST-induced immunomodulation from the view point of antigen disparity. Skin graft survival was prolonged by DST only in the combination of bm1 and B6 as already confirmed by many reports. In other combinations, skin graft survivals were not prolonged at all by DST but rather shortened. In a fully allogeneic combination between AKR and B6 in which I-E antigens or Mls-1 antigens are recognized by T-cell subsets with TCR Vbeta11 or Vbeta6, respectively, responses to stimulation by anti-Vbeta11 and Vbeta6 monoclonal antibodies were decreased by DST. Furthermore, the number of Vbeta6+ T cells was decreased in the periphery probably due to peripheral clonal deletion. In such a condition, the mixed lymphocyte reactions of B6 to AKR were reduced to some extent, but were clearly detected. In addition, skin allografts from AKR were more rapidly rejected in B6 mice given AKR spleen cells. From these results, DST seems to induce nonresponsiveness to some antigens (I-E antigens, Mls antigens and bm1 antigens in this study), but not to others. Our study also indicated that DST alone, at least in the absence of other treatments, does not contribute to allograft tolerance in fully allogeneic combinations.

Animals↗

Preoperative hyperthermia combined with chemotherapy and irradiation for the treatment of patients with esophageal carcinoma.

AIMS AND BACKGROUND: The purpose of this study was to investigate the combined effects of hyperthermia, chemotherapy and irradiation on esophageal cancer. METHODS AND MATERIAL: Since 1978, we have clinically applied hyperthermia combined with chemotherapy and irradiation (HCR therapy), to patients with carcinoma of the esophagus. The clinical results of 136 patients receiving preoperative HCR therapy were then compared with those of 107 cases undergoing preoperative chemo-radiotherapy (CR). RESULTS: A histological examination of the resected esophagus after preoperative treatment revealed that 65.4% and 50.5% of the patients responded markedly (no viable cancer cells) and moderately (more than two thirds of all cancer cells destroyed) to HCR and CR therapies, respectively (p < 0.05). The five-year survival rates were 22.3% and 13.7% in the HCR and CR groups, respectively, and the difference was statistically significant (p < 0.01). In particular, for the patients classified as TNM Stages III and IV, a significantly longer survival period was obtained with HCR therapy (p < 0.05). In addition, no severe side effects were encountered in the patients given just hyperthermia. CONCLUSION: Our clinical results suggest that preoperative hyperthermo-chemo-radiotherapy shows great promise for treatment of patients with advanced carcinoma of the esophagus.

Adult↗

Impaired blood rheology in critically ill patients in an intensive care unit.

Critically ill patients are at increased risk of thromboembolic complications. Japanese patients admitted to the intensive care unit of Gunma University Hospital were divided into critically ill (high score) and moderately ill (low score) groups according to mean Acute Physiology and Chronic Health Evaluation (APACHE) II score. White blood cell count, potassium, creatinine, immunoglobulin G and blood passage time, measured using the microchannel method, were significantly higher and the platelet aggregation score and platelet count were significantly lower in the high-score group than in the low-score group, but other haemorheological parameters did not differ significantly between the two groups. White blood cell count, potassium, creatinine, APACHE II score and levels of immunoglobulins G, A and M were positively correlated with blood passage time in all patients. Critically ill patients had impaired blood rheology, which could result from increased white blood cell count, potassium, creatinine and immunoglobulins and may be associated with the pathophysiology of the thromboembolic process.

Adolescent↗

Hyperthermia combined with chemotherapy and irradiation for patients with carcinoma of the oesophagus--a prospective randomized trial.

From 1988 to 1990, 53 patients with squamous cell carcinoma of the thoracic oesophagus underwent subtotal oesophagectomy after either preoperative hyperthermo-chemoradiotherapy (HCR therapy) or chemoradiotherapy without hyperthermia (CR therapy), in a prospective randomized trial carried out to examine the effects of hyperthermia given preoperatively. The two groups (27 patients given HCR therapy and 26 given CR therapy) were found to be comparable with regard to prognostic factors of age, site of carcinoma, TNM stage, etc. Following preoperative evaluation by an upper GI series and endoscopy, a subtotal oesophagectomy was done for all 53 patients. All the resected specimens, including the lymph nodes, were histopathologically examined, and the effects of preoperative treatment were evaluated by findings in the upper GI series and endoscopy, as well as based on the histopathology of the excised tissues. There were no viable cancer cells in the resected specimens of seven patients in the HCR therapy group (26.9%) and of two patients in the CR therapy group (7.7%). In addition, no hyperthermia complications were observed. The study suggests that preoperative HCR therapy may be a more beneficial therapy than preoperative CR therapy in patients with squamous cell carcinoma of the oesophagus who undergo a subtotal oesophagectomy.

Aged↗

A complete response of an advanced oesophageal carcinoma treated with hyperthermic chemotherapy: a case report.

A 56-year-old Japanese man with an advanced squamous cell carcinoma in the middle oesophagus was treated with a combination of hyperthermia, intravenous infusion of cisplatin (CDDP) and oral administration of oily bleomycin(BLM)-polyacrylate paste. After performing six sessions of hyperthermia treatment conducted at 42-45 degrees C for 30 min with 150 mg of CDDP and 180 mg of BLM, a subtotal oesophagectomy and lymph node dissection were performed. A histopathological study of the resected specimen showed no residual viable cancer cells either in the oesophagus or in the dissected lymph nodes. There were no side effects or perioperative complications and the patient is now healthy and leading a normal life 10 months after operation without undergoing any further treatment, at the time of writing. The effect of small amounts of CDDP and the oral application of oily BLM were thought to be strongly enhanced by hyperthermia in the treatment of oesophageal squamous carcinoma, and this regimen is therefore recommended as a safe and effective strategy, especially for preoperative treatment.

Antineoplastic Combined Chemotherapy Protocols↗

Predictive value of intracellular ATP level for cell viability after heating in malignant cells.

An adenosine triphosphate (ATP) assay is known to be a useful chemosensitivity test, which correctly reflects cell viability. We investigated the usefulness of ATP assay as a thermosensitivity test by comparing two world-wide accepted assays which included a succinate dehydrogenase (SD) assay and a colony assay. We exposed KSE-1 and KSE-2 cell lines to various degrees of hyperthermia at 42, 43 and 44 degrees C for 0.5, 1, 2, 3 and 4 h, respectively. The ATP activity for the KSE-1 and KSE-2 cell lines was 2.0 and 0.7% in change of cell viability after heating at 44 degrees C for 4 h, respectively. Colony formation rates in the KSE-1 and KSE-2 cell lines were 0.9 and 0%, respectively, whereas the SD activity of each cell line was 24.1 and 22.8%. As a whole, the ATP assay showed a closer correlation to the colony assay than the SD assay because the latter revealed a more than 20% pseudo-viability due to the response between the base and residual enzyme even after the cells had died. Thus, the ATP assay was judged to be more sensitive than the SD assay; it was also quicker than the colony assay in evaluating cell viability after heating. We propose that the ATP assay should be included as another useful thermosensitivity test for malignant cells.

Adenosine Triphosphate↗

Chemotherapy combined with or without hyperthermia for patients with oesophageal carcinoma: a prospective randomized trial.

From 1990 to 1991, 40 patients with squamous cell carcinoma of the thoracic oesophagus were admitted to our institutions and chemotherapy (oil Bleomycin p.o. and CDDP d.i.v.) either combined with or without hyperthermia was performed, in a prospective randomized trial carried out to investigate the effects of hyperthermia. The two groups (group A, consisting of 20 patients given chemotherapy alone; and group B, made up of 20 given chemotherapy with hyperthermia) were comparable with regard to various prognostic factors. Following the above treatment regimens, an oesophagectomy was done in 16 and 17 patients from groups A and B, respectively. A subjective improvement of dysphagia was seen in 8 (40.0%), and in 14 patients (70.0%), while a radiographic improvement was recognized in 5 (25.0%) and 10 cases (50.0%) in groups A and B, respectively. In the resected specimen of 16 (group A) and 17 patients (group B), histopathological evidence of the effectiveness of the treatments were recognized in 3 (18.8%) and 7 (41.2%) from groups A and B, respectively. Excluding the cases of superficial carcinoma (T1 tumour), histologic effectiveness of the treatments were recognized in 2 (14.3%) and 7 (58.3%) in groups A and B, respectively (p < 0.05). There was no difference in the occurrence of side effects between the groups. Therefore, the clinical and pathological effects were favourable in the hyperthermia combined with chemotherapy group, especially in the cases with advanced oesophageal cancer.

Aged↗

Clinicopathologic features of patients with oesophageal cancer obtaining a histological complete response for preoperative hyperthermo-chemo-radiotherapy.

From 1979 to 1993, 151 patients with resectable oesophageal cancer underwent preoperative hyperthermo-chemo-radiotherapy (HCR) followed by a subtotal esophagectomy. All resected specimens were histopathologically evaluated, and then were classified into two groups according to the efficacy of the preoperative HCR. Group A included 33 patients whose resected oesophagus was free of any cancer cells (grade 3). Group B included 118 patients, in which viable cancer cells remained in the resected specimens to various degrees (grade 1,2). The incidence of patients with well differentiated squamous cell carcinoma, node negative cases, or TNM stage I/II was significantly higher in group A than in group B (27.3% versus 9.3%, 72.7% versus 50.8%, 72.7% versus 50.8%, respectively). The recurrence rate was 33.3% (11/33) in group A, while it was 65.3% (77/118) in group B (p < 0.005). There was no case with any local recurrence in the former, while it was 8.5% (10/118) in the latter. The 1-, 3- and 5-year survival rates were 87.2%, 65.9% and 46.1% in group A, while they were 54.8%, 26.7% and 18.8% in group B (p < 0.005), respectively. Preoperative HCR may be expected of decreasing in the recurrence rate, including regional relapse when a grade 3 is obtained. Complete local control would further positively influence the prognosis.

Antineoplastic Combined Chemotherapy Protocols↗

Relationship between the expression of HLA-DR antigen and the effectiveness of preoperative hyperthermo-chemo-radiotherapy in oesophageal cancer.

Based on the hypothesis that tumour cells expressing HLA-DR antigen would easily be damaged by the local immune response during preoperative treatments, the relationship was investigated between the expression of HLA-DR antigen in the oesophageal cancer and the effectiveness of the preoperative treatment. Immunohistochemical staining for the detection of HLA-DR antigen in cancer cells from biopsy specimens obtained before undergoing preoperative hyperthermo-chemo-radiotherapy (HCR therapy) in patients with oesophageal squamous cell carcinoma was performed, and the relationship between the expression of HLA-DR antigen and the effectiveness of HCR therapy was evaluated according to a histopathologic examination of resected specimen. A total of 35 cases were examined in which 14 showed strongly positive staining (+2), 14 weakly positive staining (+) and seven negative staining (-). No significant differences in the clinicopathologic factors between the groups were observed. In the 14 strongly positive HLA-DR antigen cases, nine were markedly effective (grade 3) (64.3%), four were moderately effective (grade 2) (28.6%) and one was slightly effective or ineffective (grade 1, 0) (7.1%). In the 14 weakly positive HLA-DR antigen cases, the markedly, moderately and slightly or ineffective cases numbered four (28.6%), eight (57.1%) and two (14.3%), respectively. On the other hand, in the seven patients showing no HLA-DR expression, the markedly, moderately and slightly effective cases numbered one (14.3%), two (28.6%) and four (57.1%), respectively. A statistical difference was observed between the cases of strongly positive and negative staining for HLA-DR antigen (p < 0.05). The expression of HLA-DR antigen in oesophageal cancer cells is thus considered to potentially be a valuable factor for predicting the effectiveness of preoperative treatment.

Aged↗

Platelet aggregability and the occurrence of anastomotic leakage after esophageal reconstruction.

In 21 patients who had undergone resection and reconstruction for esophageal carcinoma, the postoperative platelet aggregability was measured and the correlation between the occurrence of anastomotic leakage and platelet aggregability was investigated. There was no statistical difference in the clinical features of the patients between those with (n = 5) and without (n = 16) anastomotic leakage. Platelet aggregability was measured by the turbidimetric method from blood samples taken preoperatively, and at 1, 3, and 7 postoperative days (POD). The average values of platelet aggregability in patients without anastomotic leakage were 81.2, 70.4, 80.1, and 81.8%, while those with leakage were 81.3, 47.6, 52.3, 70.6% preoperatively, and 1, 3, and 7 POD, respectively. Thus, platelet aggregability significantly decreased in patients with anastomotic leakage on the first postoperative day (p < .05), and then gradually recovered postoperatively as time passed. Therefore, the measurement of platelet aggregability is considered to be one of the parameters predicting the occurrence of anastomotic leakage, and a prevention in the decrease of platelet aggregability as well as its activation could become a treatment for preventing anastomotic leakage.

Aged↗

Significance of p53 protein expression in growth pattern of esophageal squamous cell carcinoma.

The significance of intraepithelial carcinoma concomitant with esophageal squamous cell carcinoma during carcinogenesis and progression of the tumor has been discussed diversely. The purpose of the current study was to elucidate the relation between p53 protein expression and the growth pattern of the squamous cell carcinoma of the esophagus with attention to coexistence of intraepithelial carcinoma. Seventy cases with squamous cell carcinoma of the esophagus surgically resected without preoperative adjuvant therapy, including 49 cases with intraepithelial carcinoma contiguous to the invasive lesion, were analyzed immunohistochemically for p53 expression. Positive immunoreactivity of p53 was found in 36 (51.4%) of 70 cases. The frequency of p53 protein expression in cases with intraepithelial carcinoma (65.3%; 32/49) was significantly higher than that (19.0%; 4/21) in cases without intraepithelial carcinoma (p<0.001). The value of invasion coefficient, which indicates a ratio of the area of invasive cancerous lesion occupied in the whole lesion, in the cases with p53 protein expression was significantly smaller than that in the cases without p53 protein expression (p<0.001). In conclusion, p53 protein expression was found to be significantly related to the coexistence and spreading of intraepithelial carcinoma contiguous to squamous cell carcinoma of the esophagus.

Carcinoma, Squamous Cell↗

Esophageal cancer and second primary brain tumor.

We report a rare case of a second primary brain tumor following esophageal cancer. A 56-year old Japanese man underwent a transhiatal esophagectomy for esophageal carcinoma. Two years after the operation, signs of increased intracranial hypertension including headache, nausea and left limb ataxia were observed. The tumor was totally removed by a suboccipital craniectomy, and the histological diagnosis was hemangioblastoma. The post-operative course was uneventful and the patient is still alive without any signs of recurrence. It is important to make a precise strategy for the second primary tumor.

Brain Neoplasms↗

HLA-DR antigen expression in squamous epithelial dysplasia and squamous cell carcinoma of the esophagus: an immunohistochemical study.

To clarify the biologic significance of esophageal squamous epithelial dysplasia, especially the similarity to carcinoma in situ, immunohistochemical investigation of HLA-DR antigen expression and lymphocyte infiltration was performed. HLA-DR antigen was expressed in 12 of the 35 invasive carcinomas (34.4%), 23 of the 38 intraepithelial carcinomas (60.5%), 21 of the 50 areas of dysplasia (42.0%) and only 2 of the 625 specimens of non-cancerous squamous epithelium (0.3%). The HLA-DR-positive rate of dysplasia localized continuous to HLA-DR-positive carcinoma was 68.4%, which was significantly higher than that for HLA-DR positive dysplasia localized continuous to HLA-DR negative cancer (11.1%) (p<0.05). In areas of dysplasia and intraepithelial carcinoma, T cell infiltration was significantly increased at the sites of HLA-DR antigen expression (P<0.01). B cell infiltration was also more common in areas of positive expression. These results suggest that HLA-DR antigen is associated with the local immune response to squamous epithelial dysplasia, and that HLA-DR antigen expression may prevent tumor invasion similarly to its role in intraepithelial carcinoma.

Adult↗

Protein kinase C activity in human gastric carcinoma.

Protein kinase C (PKC) is believed to play an important role in tumorigenesis, so we measured PKC activities of human gastric carcinomas and adjacent normal mucosae to elucidate its role for gastric carcinogenesis using PegTagtrade mark non-radioactive protein kinase C assay. The mean activities of microsomal PKC in carcinoma and normal mucosa were 449+/-179, 661+/-264 pmol/min/mg, respectively (p=0.001). Cancerous microsomal PKC activity decreased when the tumor was small, node-metastasis was negative, the depth of invasion was shallow and the histological type was differentiated. Our results suggested that PKC activity would be down-regulated in membrane of the early stage of gastric carcinoma.

Adult↗