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Biomedical subjects

H Kuwano

Publications and source records attributed to H Kuwano.

At least 19 recordsLinked to original sources

Esophageal squamous cell carcinoma occurring in the surface epithelium over a benign tumor.

The coexistence of a benign tumor and carcinoma in the same esophagus is uncommon, while the occurrence of carcinoma in the surface epithelium over a benign tumor is considered to be extremely rare. Among 587 patients with surgically resected esophageal cancer, the cases with carcinoma located over a benign tumor of the esophagus were histopathologically investigated and the carcinogenesis of such cases was discussed. Only three cases were found to have esophageal squamous cell carcinoma located over benign tumors (two were leiomyomas and one was a lipoma). All three benign tumors protruded to the esophageal surface, and the carcinoma was located just over such tumors without coexisting epithelial dysplasia. Moreover, the epithelium, except for portions around these tumors, was intact in all three cases. From these findings it was suggested that chronic stimulation of the epithelium covering the benign tumors might have induced the carcinoma.

Aged

Prospective randomized study of hyperthermia combined with chemoradiotherapy for esophageal carcinoma.

From January 1988 to June 1992, 66 patients with resectable squamous cell carcinoma of the thoracic esophagus underwent preoperative adjuvant therapy. These patients were prospectively divided into two treatment groups; 32 were treated with radiofrequency wave local hyperthermia combined with chemoradiotherapy (hyperthermochemoradiotherapy; HCR), while the remaining 34 patients were treated with chemoradiotherapy alone (CR). There were no procedural complications in either group and the postoperative mortality was zero. In the HCR group, no viable cancer cells were found within the entire 5 mm-width slices of the resected specimen in eight patients (25%), while only two (5.9%) in the CR group (P < 0.05) demonstrate no viable cancer cells. The cumulative 3-year survival rate was 50.4% in the HCR group and 24.2% in the CR group. The present prospective trial demonstrated that the addition of hyperthermia to chemoradiotherapy resulted in a better local control and an improved long-term survival when treating patients with advanced esophageal carcinoma.

Adult

Mastopathy of the accessory breast in the bilateral axillary regions occurring concurrently with advanced breast cancer.

We herein report a 41-year-old Japanese woman who demonstrated advanced cancer in the left breast occurring concurrently with mastopathy of the accessory breast tissue in the bilateral axillary regions, which appeared to be metastatic lymphadenopathy. A preoperative examination, including a mammogram, US, and CT, did not provide us with a definite diagnosis of the axillary masses: it was essential to diagnose the masses preoperatively since a bilateral mastectomy with nodal dissection is called for if the right axillary masses are metastatic from a cancer in the right breast. An intraoperative cytological examination from the bilateral axillary masses revealed adenosis with fibrocystic changes in the accessory breast tissue. We therefore performed a modified radical mastectomy only on the left side. The patient was thus saved from an unnecessary mastectomy of the right breast. Based on our experience, we wish to emphasize that the accessory breast tissue should be considered for a differential diagnosis when evaluating the axillary masses in order to avoid over-surgery, especially when a patient has been diagnosed to have massive breast cancer. An intraoperative cytological examination is strongly recommended to reach a final diagnosis in such confusing cases.

Adult

The prognostic significance of the cytophotometric DNA content and its relationship with the argyrophilic nucleolar organizer regions (AgNOR) and proliferating cell nuclear antigen (PCNA) in oesophageal cancer.

We examined the DNA pattern, AgNOR number and PCNA-positive ratio (PCNA ratio) from biopsy specimens of oesophageal carcinoma, and attempted to identify any prognostic factors for oesophageal carcinoma. DNA analysis: the cell nuclear DNA content was measured and the distribution pattern of the DNA content was grouped into four types according to the ploidy pattern (n = 182). The survival rate of patients with high-ploidy tumours (type III and IV) was shorter than that for low-ploidy tumours (type II), (P < 0.05). AgNOR number (n = 99) and PCNA ratio (n = 41): the AgNOR number and PCNA ratio were measured from 100 cancer cells in each specimen. Both the high-AgNOR-number patients (> or = 5) and the high-PCNA-ratio patients (> or = 35) demonstrated poorer prognoses than the low-rate patients (P < 0.05). These results suggest that the DNA pattern, AgNOR number and PCNA ratio may thus reflect the proliferative activity of tumours and therefore also offer the possibility of interdependence among these three factors.

Aged

The long-term results of pre-operative hyperthermo-chemo-radiotherapy for oesophageal carcinoma--a comparison with preoperative radiation therapy alone.

The long-term results of patients with oesophageal carcinoma treated with pre-operative hyperthermo-chemo-radiotherapy (HCR) and pre-operative radiation therapy alone were compared. Twenty-six patients treated with pre-operative hyperthermo-chemo-radiotherapy (HCR Group) and 25 treated with radiation therapy alone (R Group), which demonstrated histopathologically marked effective results (Grade 3), were entered into the study. The 3-year survival rates after oesophagectomy in the HCR Group and the R Group were 67.4% and 41.8%, respectively, while the 5-year survival rates were 50.5% and 34.9%, respectively. Thus post-operative prognosis in the HCR Group was significantly more favourable than that in the R Group (P < 0.05). The local recurrence and distant metastasis rate in the HCR Group was significantly less than in the R Group (P < 0.01). This significant difference in prognosis was thought to be due to the reinforced effects of local regulation by hyperthermia and the systemic control of micrometastasis by chemotherapy in addition to radiation. Our data suggest that for carcinoma of oesophagus, pre-operative hyperthermo-chemo-radiotherapy contributes to prolonged post-operative survival while reducing both local recurrence and micrometastasis.

Antineoplastic Combined Chemotherapy Protocols

Histological suggestions of 'paratransformation' in oesophageal squamous cell carcinoma.

We have postulated that oesophageal squamous cell carcinoma arises from multifocal areas and not from one cell, and we present the circumstantial evidence for field carcinogenesis in oesophageal cancer. Among 290 cases examined with oesophageal squamous cell carcinoma, lymphatic permeation or intramural metastasis was evident in 110 cases. Of these carcinomatous transformation of the epithelium adjacent to either lymphatic vessel permeation or intramural metastasis of the squamous cell carcinoma was recognized in six cases. It is considered that the cancer tissue either in the lymphatic vessel or intramural metastasis promotes a malignant transformation of the squamous epithelium over these foci. 'Paratransformation' is therefore thought to be one of the potential models of origin for oesophageal squamous cell carcinoma.

Aged

Resection margin for squamous cell carcinoma of the esophagus.

OBJECTIVE: The safe resection margin in esophagectomy for esophageal squamous cell carcinoma (SCC) was determined based on the extent of epithelial and subepithelial accessory lesions from the main lesions of esophageal SCC. BACKGROUND: There have been many reports on the high incidence of a positive resection margin for esophageal cancer. Although there were some studies on the relationships of the proximal clearance to postoperative local recurrence, no pathologic study on the resection margin has been reported. METHODS: Four hundred twenty specimens of a whole resected esophagus were examined histopathologically and the longitudinal length from the main lesion to the five types of accessory lesions was measured on microscopic slides. RESULTS: Contiguous intraepithelial carcinoma existed in 69 (46%) of 150 sites of main lesions restricted to the mucosa or submucosa and subepithelial lesions existed in 131 (54%) of 245 sites and 82 (55%) of 150 sites of main lesions invading an adventitia and into neighboring structures, respectively. The risk of a positive resection margin due to subepithelial lesions was below 5% at 10 mm in the main lesion, restricted to the submucosa or the muscularis propria, and at 30 mm in the main lesion, invading the adventitia in the potentially curative operation cases. CONCLUSION: These clearances of the resection margin, in which the risk of a positive resection margin is below 5%, are acceptable, although these clearances should only be accepted after the extent of epithelial accessory lesions is accurately determined by the Lugol's stain method.

Adult

Successful simultaneous resection and reconstruction of abdominal aortic aneurysm and esophageal cancer.

A simultaneous resection and reconstruction of abdominal aortic aneurysm (AAA) and esophageal cancer was performed on an eighty-year-old Japanese man. In spite of his advanced age, preoperative assessments revealed that the general functions of the patient were quite satisfactory. An esophagram, endoscopy and CT scan all demonstrated the esophageal cancer to be in a relatively early stage without any lymph node metastasis, while the CT scan demonstrated an infrarenal type of fusiform abdominal aortic aneurysm with a maximum transverse diameter of 7.0 cm. A simultaneous resection and reconstruction of both the AAA and esophageal cancer was performed on August 8, 1991. First, the operation for AAA was done through a retroperitoneal approach, and next, a resection and reconstruction of the esophageal cancer was performed with a right thoracotomy and laparotomy using the gastric tube as an esophageal substitute. The postoperative course was uneventful except for a temporary purulent discharge through the mediastinal drain. The patient was discharged on the 56th postoperative day. Therefore, when the general conditions are considered to be tolerable for operation, such a simultaneous operation may be indicated even inpatients of advanced age by utilizing isolated approaches and taking great care.

Aged

Extensive spreading carcinoma of the esophagus with invasion restricted to the submucosa.

OBJECTIVES: The aim of this study was to examine the clinicopathological features of extensive spreading type of squamous cell carcinoma (SCC) of the esophagus with invasion restricted to the submucosa. METHODS: Thirty-eight submucosal SCC were studied histopathologically, and five of these 38 submucosal SCC, which demonstrated an extensive spreading-type SCC in which the size of the SCC was over 5 cm in longitudinal length while extending entirely across the esophageal lumen in a circumferential spread, are described in detail. RESULTS: The extent of SCC depended mainly on the extent of intraepithelial carcinoma (IEC) and ranged from 50 to 135 mm in longitudinal length. IEC existed continuously in four cases, and multiple IEC existed separately in one case. An epithelium showing dysplasia was present in all cases, and the involvement of the glands and ducts by IEC was present in two cases. There was only one invasive part of SCC observed in one case, and three to 10 invasive parts of SCC were observed in the other four cases; various features of invasion, including an invasive SCC from the esophageal glands and ducts, were also present. CONCLUSIONS: The extensive spreading-type SCC of the esophagus, which was considered to result from the widespread or multiple carcinomatous changes of the esophageal epithelium, was found to not be as rare as generally thought. The multiple and various features of the invasive parts of SCC suggested the simultaneous development of a downward invasion of SCC at different areas in extensive IEC.

Adult

The clinical characteristics of patients with synchronous squamous cell carcinoma of the esophagus and hepatocellular carcinoma.

An ongoing analysis of 762 patients with esophageal cancer revealed 4 (0.52%) male patients with synchronous hepatocellular carcinoma (HCC). A long history of habitual alcohol intake and heavy cigarette smoking was recognized in all four patients and, therefore, the possibility of these two factors being independent risk factors for this double cancer was suggested. Palliative treatment was undertaken since either one or both cancers were too far advanced, or because liver function was poor even in those patients with resectable cancers. The prognosis correlated more closely to the TNM stage of esophageal cancer rather than the HCC and the causes of death were related to the esophageal cancer in all four patients. These findings suggest that, in patients with this combination of double cancer, the state of the esophageal cancer may be a more reliable prognostic factor than that of the HCC and thus, the curability of esophageal cancer is of primary importance.

Aged

Pre-operative estimation of complete resection for patients with oesophageal carcinoma.

Three hundred and seventy-nine patients were studied retrospectively regarding the possibility of a complete resection of the oesophageal carcinoma based on the combined findings of pre-operative oesophagogoraphy and computed tomography (CT). One hundred and four out of 129 patients (96.1%) having lesions which did not demonstrate all three of the aforementioned factors (a lesion shorter than 8 cm, a normal oesophageal axis, and normal contact of the lesion with neighboring organs in CT) underwent a complete resection of the oesophageal lesion. Fifty-three percent of the patients (52/97) with a lesion showing only one of these factors had a complete resection. Whereas, on the other hand, a complete removal of the malignancy was only possible in 22% of the patients with two or all three of the findings. Moreover, as a result of further analysis limited for resected cases, the number of positive factors in these pre-operative findings correlated with the advancement of the surgical stage, which reflected a curability in surgery and a rate of postoperative complications. In order to make adequate plans for the treatment of patients with advanced oesophageal cancer, the finding of (i) the length of lesion, (ii) a deep ulceration and deformity of the oesophageal axis and (iii) any abnormal contact in CT, are considered to be very useful.

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

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