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Biomedical subjects

H Kuwano

Publications and source records attributed to H Kuwano.

At least 163 records · Page 9Linked to original sources

Expression of Sialyl-Tn antigens in normal squamous epithelium, dysplasia, and squamous cell carcinoma in the esophagus.

Two monoclonal antibodies, TKH2 and B72.3, directed toward the Sialyl-Tn antigen (SA 2, 6GalNAc alpha-O-Ser/Thr), were examined immunohistochemically to analyze the expression of these antigens in 20 areas of normal squamous epithelium, 12 lesions of dysplasia, and 86 cases of squamous cell carcinoma including 32 with superficial carcinoma in the esophagus. No expression of TKH2 or B72.3 was found in the normal squamous epithelium. Among the 12 lesions of dysplasia only one expressed TKH2. In carcinoma the expression of TKH2 and B72.3 was found in 40 (47%) and 21 (24%) of the 86 carcinomas, respectively; however, the number of positive malignant cells with TKH2 and B72.3 totaled less than half that in the tissue, and no relationship was found between either prognosis or lymph node metastasis and the expression of Sialyl-Tn antigen. These results indicate that Sialyl-Tn antigen appears in the process of malignant transformation or tumor progression in esophageal squamous cell carcinoma; however, the positive expression of Sialyl-Tn antigen was not directly connected to either prognosis or lymph node metastasis.

Antibodies, Monoclonal↗

Surgical treatment of esophageal carcinoma in patients eighty years of age and older.

Before 1979, no patient 80 years of age or older had been operated on at our institution for esophageal cancer, while in the middle period (1980-1984), three patients were operated on, and postoperative pulmonary complications and operative death occurred in 66.7 and 33.3%, respectively. However, in the recent period (1985-1990), there was no postoperative morbidity or mortality in the five cases over age 80. On the other hand, there were 12 patients over age 80 who did not undergo operation, of whom all died of cancer. In the eight operated patients over age 80, two cases are still alive 17 and 34 months after operation. According to the above findings, when the patient's general condition is evaluated to be sufficient to tolerate the operation and the cancer is judged to be resectable, esophageal resection is thought to be indicative in all patients over eighty.

Aged↗

Cytophotometric DNA content and argyrophilic nucleolar organiser regions of oesophageal carcinoma.

The cytophotometric DNA content and the argyrophilic nucleolar organiser regions (AgNORs) of biopsy specimens taken before undergoing any treatment were examined in 91 surgically treated oesophageal carcinoma cases. There was a significant linear dependence between the mean DNA content and the number of AgNOR per nucleus (AgNOR number) (r = 0.615, P < 0.001). The DNA distribution pattern and the range of the AgNOR number also showed a significant correlation (P < 0.01). Twenty three of 28 cases with a low AgNOR number (< 4) were then determined to have a diploid pattern (type II), while 17 out of 22 cases with a high AgNOR number (> or = 6) had high ploidy values (type IV). The patients with a type II DNA distribution pattern and a low AgNOR number thus showed a good post-operative course with a 5 year survival rate of 55.2%, whereas no patients survived over 4 years among the 17 cases with both a type IV DNA pattern and a high AgNOR number (P < 0.001). These data thus demonstrate the close relationship between cytophotometric DNA content and AgNOR number and suggest that the combined detection of these two parameters, using biopsy specimens, should be of benefit in making an accurate preoperative evaluation of prognosis for patients with oesophageal carcinoma.

Adult↗

[Clinical study of hyperthermia combined with chemotherapy in the treatment of carcinoma].

From November 1990 to July 1991, data on 21 patients with primary squamous cell carcinoma of the thoracic esophagus were used for the present study. Among these 21 cases, 10 received only chemotherapy (Group A) and 11 were given hyperthermo-chemotherapy (Group B). Six and nine cases were surgically treated after preoperative chemotherapy or hyperthermo-chemotherapy in Group A and B, respectively. After treatment of Group A or B, 5/10 patients in Group A (50%) mentioned improvement in swallowing capability, as did 9/11 patients (81.8%) in Group B. In the upper GI series, done after treatment, a complete response was seen in one case in Group B, while a partial response was obtained in 3 patients (30%) and in 3 patients (27.3%) with minimal response in Group A and B, respectively. A histopathologic examination of the resected specimen revealed marked effectiveness in 0 and one (11.1%) patients, and moderate effectiveness in 1 (16.7%) and 2 (22.2%) patients in Group A and B, respectively. Consequently, this intensive treatment should be expected to greatly improve local control without causing either any severe side effects or complications.

Antineoplastic Combined Chemotherapy Protocols↗

Lugol staining pattern and histology of esophageal lesions.

To analyze the relationship between Lugol unstained areas and their histologic features, we applied the Lugol test to 24 specimens of resected esophagus. The staining patterns were graded into four types: grade I, hyperstaining; grade II, normal greenish brown staining; grade III, less intense staining; and grade IV, unstained. Most of the grade IV lesions were invasive carcinomas, carcinomas in situ, or severe dysplasia. The carcinomas in situ and the intraepithelial extension of the carcinomas, which were difficult to detect, were clearly shown as grade IV. On the other hand, moderate to mild dysplasia or atrophy showed grade III staining. Grade IV lesions showed well-demarcated sharp margins, whereas grade III lesions showed ill-demarcated dull margins. The grade III carcinomas, however, by the Lugol test, showed well-demarcated margins. Histologic evaluation disclosed that the staining intensity reflected well the thickness of the glycogen-containing cell layer in the lesion. The sharpness of the margin reflected the abrupt or gradual change from the glycogen-containing to non-containing cell layers. These findings suggest 1) the usefulness of the staining pattern of the Lugol test for the diagnosis of esophageal lesions such as squamous cell carcinoma and severe dysplasia, and 2) the usefulness of the Lugol test for precise delineation of the proximal resection line during surgery of esophageal carcinomas with unexpected wide extension.

Atrophy↗

[Multidisciplinary treatment of esophageal cancer].

Hyperthermia combined with irradiation and chemotherapy was prescribed for patients with resectable squamous cell carcinoma of the esophagus. The long-term results were compared between two groups of patients, one treated with chemotherapy, radiotherapy and hyperthermia (HCR), the other with chemotherapy and radiotherapy, but not hyperthermia (GR). The five-year survival rates of patients with resectable carcinoma, given preoperative HCR or CR, were 22.3 and 13.7 per cent, respectively. In particular, for the patients classified as Stages III and IV, a longer survival period was obtained with HCR (p < 0.05). Since 1990, we applied a protocol of prospective randomized study for neoadjuvant chemotherapy. We presented the results of comparison between two groups, one of which was treated by chemotherapy alone and the other by chemotherapy combined with hyperthermia, for both resectable and non-resectable cases. Data on 21 patients with a primary squamous cell carcinoma of the thoracic esophagus were included in the present study. Among these 21 cases, 10 received only chemotherapy (Group A), and 11 were treated by hyperthermo-chemotherapy (Group B). In each group, 6 and 9 patients each were surgically treated. According to our regimen, in Group A, 30 mg of oil bleomycin (BLM) orally six times, and 50mg div. of cisplatin (CDDP) triplicate, were administered during three weeks, respectively. Besides chemotherapy, RF intraluminal hyperthermia was performed six times just after administration of BLM in Group B. There was no significant difference of prognostic factors between groups, and all the patients tolerated well the treatment modalities. The overall efficacy (% CR+PR+MR) of Group A and B was 30.0% and 63.6%, respectively. Histopathological evaluation of the effectiveness was 16.7% and 33.3% in Groups A and B, respectively. Thus, 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. Moreover, postoperative adjuvant therapies were also important, and choice of the treatment according to the status of carcinoma and the patient's condition is essential.

Bleomycin↗

The sensitivity of hyperthermo-chemo-radiotherapy for neoplastic cells in vitro on contact-sensitive plates.

On plastic dishes, the Chinese hamster cell line (V-79) easily formed colonies and enabled us to examine the effects of various treatments utilizing a colony formation assay while a different human cancer cell line (KSE-1) was found to have a low colony-forming ability which made it difficult to examine when using only a small number of cells. However, on the contact-sensitive plate (CSP), the KSE-1 line was able to form a sufficient amount of colonies in order to conduct examinations. Using CSPs, we were able to investigate the killing effects of various treatments on two malignant cells (V-79 and KSE-1). For the V-79 cells, hyperthermo-chemo-radiotherapy (HCR) was observed to be more effective than any other treatment. For KSE-1 cells, on the other hand, bleomycin had little killing effect, while both radiotherapy alone or hyperthermo-radiotherapy in doses of more than 4 Gy X-ray were found to be effective. These results indicated that it is necessary to examine the sensitivities of cells to different treatments in clinical cases in order to avoid non-effective treatments. In this report, we suggest that the use of CSPs allows for the effective examination of the effects of HCR while using only a small number of malignant cells, which have a low cloning efficiency on plastic surfaces.

3T3 Cells↗

Long-term results of esophagectomy for early esophageal carcinoma.

In this paper we report on the long-term results achieved in 75 patients with superficial carcinoma of the thoracic esophagus who have been treated since 1965 with esophagectomy at our institute. In three of these patients, the carcinoma was limited to the epithelium (intra-epithelial carcinoma), while in 13 cases it was confined to the mucosa, and in 59 cases to the submucosa. There was no lymph node metastasis in patients with intra-epithelial or mucosal carcinoma, but lymph node involvement was found in 13 (22.0%) of the 59 cases of submucosal carcinoma. The five-year survival rate of patients with intra-epithelial carcinoma and mucosal carcinoma was 100%, which was significantly better than that for carcinoma invading the submucosa (49%). The five-year survival rate for patients with lymph node involvement was only 46%, which was significantly worse than that for patients without lymph node involvement (60%). No recurrence occurred in patients with intra-epithelial carcinoma or mucosal carcinoma, while recurrent disease occurred in 19 (32.2%) of the 59 patients with submucosal carcinoma. Lymph node recurrence and hematogenic recurrence such as lung and bone metastasis were the most frequent developments in patients with submucosal carcinoma of the esophagus.

Adult↗

Endoscopic ultrasonography in the diagnosis of an early esophageal carcinoma.

Patients with epithelial or mucosal carcinoma of the esophagus are considered to have a much better prognosis than those with submucosal carcinoma, although both lesions are classified as superficial carcinomas of the esophagus. With this in mind, we evaluated the usefulness of endoscopic ultrasonography for pre-operatively distinguishing either epithelial or mucosal carcinoma from submucosal carcinoma by comparing the results of endoscopic ultrasonography with the histological findings established in resected specimens. Between 1987 and 1991, 26 patients with no pre-operative treatment were confirmed histologically to have epithelial (2 cases), mucosal (11 cases) or submucosal (13 cases) carcinomas of the esophagus. In 13 patients with epithelial or mucosal carcinoma, 10 were correctly diagnosed with endoscopic ultrasonography (76.9%), while the remaining 3 were overdiagnosed as being submucosal. In 13 patients with submucosal carcinoma, 12 were correctly diagnosed by endoscopic ultrasonography (92.3%), although another case was overestimated. Including one patient with an advanced carcinoma who was underdiagnosed by endoscopic ultrasonography as having a submucosal lesion, the overall accuracy of endoscopic ultrasonography was 81.5% for diagnosing the depth of invasion of a superficial esophageal carcinoma. The above results show that endoscopic ultrasonography can provide surgeons with important information in the pre-operative assessment of a superficial esophageal carcinoma.

Adult↗

Histopathology of early esophageal carcinoma and squamous epithelial dysplasia.

To examine the histogenesis of esophageal cancer and the pathological relationship between dysplasia and carcinoma of the esophagus, 44 cases of superficial esophageal carcinoma (restricted to within the submucosal layer) who received no pre-operative treatment were reviewed retrospectively. There were 40 dysplastic lesions in 17 cases (38.6%) and epithelial dysplastic lesions were classified into 6 with mild, 17 with moderate and 17 with severe, degrees of dysplasia. Although the continuity of dysplastic lesions with the carcinomatous areas was not frequent (35.0%), it was more often encountered in severe dysplasia than in moderate or mild dysplasia, suggesting some relationship between the severity of dysplasia and carcinoma. In the cases with a dysplastic lesion, multiplicity of squamous cell carcinoma was more frequently seen (p < 0.01), suggesting a multicentric occurrence of dysplastic lesions and carcinomas.

Adult↗

Carcinomatous invasion and lymphocyte infiltration in early esophageal carcinoma with special regard to the basement membrane. An immunohistochemical study.

We examined 24 cases of superficial esophageal carcinoma and evaluated 94 areas, including 43 intra-epithelial (ep), 36 mucosal (m) and 15 submucosal (sm) areas, using the immunohistochemical staining of laminin to detect the basement membrane. The staining pattern was divisible into three patterns, i.e., continuous, fragmentary and defective. Defective patterns were observed in 14%, 53%, and 73% of the ep, m, and sm lesions, respectively (p < 0.01). With regard to the degree of lymphocyte infiltration, 77% of the continuous areas were accompanied by a low lymphocyte infiltration, while 56% of the defective areas were accompanied by dense infiltrations with follicle formation. Lymphocyte infiltration was thus statistically significantly (p < 0.01) more closely associated with the defective areas than with the continuous areas. Furthermore, urokinase-type plasminogen activator was detected immunohistochemically in 11.1% of the defective areas, and in none of the continuous areas. These findings suggested 1) that superficial esophageal carcinoma might progress while destroying the basement membrane, and 2) that as host immune reactions lymphocytes might infiltrate the lesions where the basement membranes were destroyed and cancer cells exposed to the underlying layer. The findings also suggested the possibility that the degradation of the basement membrane might be caused by proteolytic enzymes produced by cancer cells.

Adult↗

The evaluation of submucosal carcinoma of the esophagus as a more advanced carcinoma.

Of 75 patients with superficial esophageal carcinoma, there were 16 cases with epithelial or mucosal, and 59 cases with submucosal, lesions. The incidence of nodal metastasis in patients with epithelial or mucosal carcinoma was zero, and the 5-year survival rate was 100%. However, 13 out of 59 cases (22.0%) with submucosal carcinoma were accompanied by nodal involvement, and the rate of vessel invasion was 27.1% (16/59). Even in 46 cases of submucosal carcinoma without nodal involvement, there were 13 cases (22.1%) with vessel invasion. The 5-year survival rate of the 26 submucosal cases with either nodal metastasis or vessel invasion was 37.6%, and even that of the 33 cases with neither lymph node metastasis nor vessel invasion was 60.0%. On the other hand, of the 74 patients with carcinoma invading the muscularis propria, there were 35 cases (47.3%) without nodal metastasis and 27 cases (36.5%) which were also free of vessel invasion. The 5-year survival rate of the former was 32.6%, and of the latter 33.1%. On the basis of these findings, we wish to emphasize that submucosal carcinoma should be classified as an advanced carcinoma.

Adult↗

Mediastinal drainage prevents fatal pyothorax from anastomotic leakage after intrathoracic anastomosis in reconstruction for carcinoma of the esophagus.

In our experience, anastomotic leakage occurred in five of 69 patients with intrathoracic anastomosis after resection of carcinoma of the esophagus. In the early period, only an ordinary right thoracic drain was put in place, and when leakage occurred, two patients died because of pyothorax, while one patient was saved by surgical drainage. However, in the recent period, in addition to the ordinary right thoracic drain, another drain has also been placed just distal to the anastomosis through the esophageal hiatus through the abdominal cavity, exiting the abdominal wall. After such procedure, drainage has been adequate without any occurrence of pyothorax, even when anastomotic leakage occurred, as in the two most recent instances. Therefore, unless drainage is inadequate and surgical drainage is indicated, as in instances of necrosis of substitutes, mediastinoabdominal drainage seems to be effective in the treatment of intrathoracic anastomotic leakage.

Aged↗

Secondary early carcinoma in a reconstructed gastric tube after subtotal esophagectomy for early carcinoma of the esophagus.

A 70-year-old man was found to have a moderately differentiated squamous cell carcinoma in the mid-esophagus on X-ray and endoscopy. These examinations revealed no lesion in the stomach at that time. Ten days after termination of preoperative hyperthermo-chemo-radiotherapy (HCR), a subtotal esophagectomy and gastric tube reconstruction via the retrosternal route were performed (pTNM stage I). Seven months later, another early cancer was detected in the reconstructed gastric tube. Via a median sternotomy, a wedge resection of the gastric tube was performed, and histopathological studies revealed a well-differentiated adenocarcinoma, which was limited to the submucosa (pTNM stage I). The patient has since done well with no signs of recurrence for the twenty-two months that have elapsed since the second operation was performed. Since the incidence of double cancer in the esophagus and stomach is high, and cases such as that described here will be detected more and more frequently in the future, not only a thorough investigation of a stomach intended for use in the reconstruction of the esophagus, but also strict postoperative checkups of the gastric tube when the esophagus has been reconstructed using the stomach must be considered of great importance.

Adenocarcinoma↗

A flow cytometric analysis of DNA content in primary and metastatic lesions of esophageal squamous cell carcinoma.

BACKGROUND: DNA content of malignant tumors has been considered a significant prognostic factor, but intratumor variations in DNA content and differences in DNA content between primary and metastatic lesions have been found in various tumors. METHODS: DNA indexes of multiple samples obtained from different sites in each tumor were determined by flow cytometry (FCM) in 27 esophageal squamous cell carcinomas. RESULTS: Intratumor variation in DNA indexes in primary lesions was found in 10 (37%) of the 27 specimens. Of the rest, all DNA indexes were diploid in 5 and all identically aneuploid in 12 samples. A DNA index differing from that of the metastatic lesion was found in four (50%) of eight primary lesions; however, a component of the DNA index identical to that of metastatic lesion was found in seven (88%) of eight primary lesions. CONCLUSIONS: Recurrence after a "curative" operation was frequent in patients with a tumor that had an aneuploid DNA index, with or without a variation in DNA indexes. There was no recurrence in the five patients with tumors that had only a diploid DNA index. These results suggest that differences in DNA content between primary and metastatic lesions reflect intratumor variation in DNA content in the primary lesions. The presence of a tumor cell population with an aneuploid DNA content, even when the DNA content varied in the primary lesion, may indicate an aggressive clinical course in patients with esophageal squamous cell carcinoma.

Adult↗

Detection of human papillomavirus DNA in esophageal carcinoma in Japan by polymerase chain reaction.

BACKGROUND: Human papillomaviruses (HPV) have been implicated strongly in the pathogenesis of human squamous cell carcinomas, especially of anogenital carcinomas. Some pathologic changes of the esophagus may be one of the candidates for HPV etiology, but the role of HPV infections in the carcinogenesis of the esophagus remains to be clarified. METHODS: To elucidate the association of HPV with carcinogenesis of the esophagus, 45 biopsy samples of esophageal squamous cell carcinomas were examined for the presence of HPV DNA by polymerase chain reaction (PCR). Primers for PCR were (1) consensus primers (CP) for the simultaneous amplification of the E6-E7 regions of cancer-associated HPV types (HPV 16, 18, 31, 33, 52b, and 58), which have been shown to have transforming activities; (2) type-specific primers (SP16, SP18) for the E7 regions of HPV 16 and HPV 18, respectively; and (3) general primers (GP) for the simultaneous amplification of the L1 regions of HPV 6, 11, 16, 18, 31, and 33. RESULTS: PCR using CP first was done for screening and showed that 3 (6.7%) of 45 specimens contained HPV 16 or HPV 18 DNA, the oncogenic high-risk HPV types. This was confirmed by SP16 and SP18 PCR. However, no HPV DNA was detected by PCR using GP. These results suggested that the HPV DNA detected might be integrated into the cell genome with their transforming genes retained and their late regions deleted. CONCLUSIONS: Most oncogenic types of HPV (HPV 16 and HPV 18) were detected by PCR in carcinomas of the esophagus. Thus, HPV might play a role, although at a low frequency, in carcinogenesis of the esophagus.

Base Sequence↗

A farnesyl arabinoside as an enhancer of glucose transport in rat adipocytes from a soft coral, Sinularia sp.

Separation of a lipophilic extract of a soft coral, Sinularia sp., assayed by enhancement of glucose transport in rat adipocytes, gave farnesyl 4-O-beta-D-arabinopyranosyl-beta-D-arabinopyranoside-2,2',3- triacetate (1a) whose structure was determined by spectroscopy. Enhancers of glucose transport may be useful for the prevention and treatment of diabetic disorders.

Adipose Tissue↗

Serial histologic investigation of squamous epithelial dysplasia associated with carcinoma of the esophagus.

Esophageal dysplasia and carcinoma were reviewed in the surgical specimens obtained from 37 patients with squamous cell carcinoma and 4 with adenocarcinoma; special attention was paid to the continuity of both lesions. Two hundred forty dysplasias and 113 carcinomas in situ (CIS) were recognized in the squamous cell carcinoma cases and 2 dysplasias and no CIS in the adenocarcinoma cases. The CIS often was accompanied continuously by severe dysplasia rather than mild or moderate dysplasia, suggesting some relationship between the CIS and the severity of dysplasia. However, many dysplastic lesions were located separately from the carcinoma. The frequency of appearance of the dysplasia near the CIS was low (11%), demonstrating a negative dysplasia-CIS sequence in many of the esophageal cancers. Lymphocytic infiltration was investigated further beneath the dysplasia or CIS. The degree of lymphocytic infiltration with lymphoid follicles correlated with the severity of dysplasia and was the highest in CIS.

Adenocarcinoma↗