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Biomedical subjects

S Kazama

Publications and source records attributed to S Kazama.

At least 19 recordsLinked to original sources

Chromosome 18q deletion and Smad4 protein inactivation correlate with liver metastasis: A study matched for T- and N- classification.

Smad4 protein, whose gene is coded at chromosome 18q21.1, is an important tumour suppressor that mediates transforming growth factor-beta. It has been reported that inactivation of the Smad4 gene and allelic loss of chromosome 18q correlate with liver metastasis and poorer prognosis in colorectal cancers. Utilising a recently developed method of immunohistochemical staining for Smad4 protein, we focused on the specific impact of Smad4 protein expression on liver metastasis in colorectal cancer. We also evaluated the association between chromosome18q deletion and liver metastasis. We selected 20 colorectal cancers with liver metastasis for the experimental group, and 20 cases without liver metastasis for the control. In order to exclude the influence of lymph node metastasis, all cases were lymph node negative. In addition, the two groups were matched for tumour depth, tumour differentiation and tumour location. We compared the expression level of Smad4 protein immunohistochemically in these 20 matched pairs. We also compared the loss of heterozygosity status at chromosome 18q in these 20 matched pairs. Immunohistochemical staining revealed a significant difference (P = 0.024) in the level of Smad4 protein between the two groups. We also observed a significantly different (P=0.0054) ratio of allelic deletion at chromosome 18q21. Smad4 protein expression level and allelic loss at 18q21 are associated with the process of liver metastasis in colorectal cancers evaluated when excluding clinical and pathological features except for liver metastasis.

Adenocarcinoma↗

Tumour budding at the deepest invasive margin correlates with lymph node metastasis in submucosal colorectal cancer detected by anticytokeratin antibody CAM5.2.

In the past few years, tumour budding at the invasive margin has been reported as a new risk factor for lymph node metastasis in advanced colorectal cancers, but it is sometimes difficult to detect tumour budding in submucosal colorectal cancer by haematoxylin and eosin staining. We immunohistochemically examined tumour budding at the deepest invasive margin of 56 surgically resected submucosal colorectal carcinomas using anticytokeratin antibody CAM5.2, furthermore checked by AE1/AE3, and determined the relation between tumour budding and clinicopathological factors. Moreover, we used the monoclonal antibody D2-40 for immunohistochemistry to detect lymphatic involvement. Tumour budding was detected in 42 cases (75.0%), and the budding-positive group showed a significantly higher rate of lymph node metastasis (including isolated tumour cells) (16/42 vs 0/14; P=0.004) than the budding-negative group. The sensitivity and negative predictive value of tumour budding alone for lymph node metastasis were superior to those of lymphatic invasion alone. Furthermore, the specificity and positive predictive value of the combination of either lymphatic invasion or tumour budding were superior to those of lymphatic invasion alone. Tumour budding detected immunohistochemically by using CAM5.2 is a newly found risk factor for lymph node metastasis and may help to avoid oversurgery in the future.

Adenocarcinoma↗

Genetic characterization of colorectal cancers in young patients based on chromosomal loss and microsatellite instability.

BACKGROUND: In recent studies a high frequency of microsatellite instability among colorectal cancers in young patients has been reported, but the frequency of microsatellite instability (MSI) and chromosomal instability among colorectal cancers in young patients has not yet been fully elucidated. Only one report showed an increased loss of heterozygosity (LOH) ratio at 9p locus, which harbors tumor suppressor genes p16. The LOH and MSI status among colorectal cancers in young patients was examined. METHODS: Twenty-five patients under 40 years of age diagnosed with colorectal cancer were examined for MSI and LOH using 17 microsatellite markers, and also p16 expression patterns were evaluated by immunohistochemistry and methylation status of the p16 gene was assessed by methylation-specific PCR. RESULTS: MSI was observed in only one case (4%). LOH at 2p, 5q, 9p, 11q, 17p, and 18q was observed in 41%, 59%, 42%, 35%, 46%, and 56% of cases, respectively. Eighty-three percent of patients showed p16-positive expression patterns. Fifty percent of colorectal cancers in young patients exhibited p16 methylation (3/6). CONCLUSIONS: Our study demonstrated that colorectal cancers in young patients without MSI showed a high frequency of LOH at the 9p locus. However, LOH status at 9p and p16 expression pattern did not show a significant correlation. Other tumor suppressor genes on the 9p, with the exception of p16, may play an important role in the carcinogenesis of colorectal cancers in young patients.

Adenocarcinoma↗

Earlier surveillance colonoscopy programme improves survival in patients with ulcerative colitis associated colorectal cancer: results of a 23-year surveillance programme in the Japanese population.

Patients with long-standing ulcerative colitis (UC) are known to have an increased risk for the development of colorectal cancer (CRC). The aim of this study was to clarify the cumulative risk for the development of dysplasia or invasive cancer and the effectiveness of surveillance colonoscopy in the Japanese population. A total of 217 patients received a total of 1027 surveillance colonoscopies between January 1979 and December 2001 at the University of Tokyo hospital. Patients with invasive cancer found in the surveillance group were compared to those referred to our hospital from the other hospitals without surveillance colonoscopy. Surveillance colonoscopy confirmed 15 patients with definite dysplasia. Of these, five were proved to have invasive cancer in the resected specimens. The cumulative risk for the development of invasive cancer at 10, 20, and 30 years was 0.5, 4.1, and 6.1%, respectively, while that for the development of definite dysplasia at 10, 20, and 30 years was 3.1, 10.0, and 15.6%, respectively. All the patients with invasive cancer in the surveillance group remained alive, while three out of four patients in the nonsurveillance group died. Our surveillance programme is useful for detecting UC-associated CRC, and survival may be improved by surveillance colonoscopy.

Adolescent↗

Prediction of tumor radiosensitivity in rectal carcinoma based on p53 and Ku70 expression.

The identification of predictive indicators of radiosensitivity is extremely useful in selecting patients suited for preoperative radiotherapy and avoiding unnecessary preoperative treatment. In this study, we evaluated the possible role of the immunohistochemical expression pattern of p53 and Ku70 protein in determining tumor radiosensitivity in rectal cancer before preoperative irradiation. We examined pretreatment biopsy materials from 111 patients by immunohistochemistry. The expression pattern of p53 and Ku70 was evaluated for association with tumor radiosensitivity, which was defined according to the criteria of the Japanese Research Society for Cancer of the Colon and Rectum. There was a significant correlation between the expression pattern of p53 and tumor radiosensitivity (P = 0.045); Ku70 and tumor radiosensitivity (P < 0.001); and the combination of p53 and Ku70, and tumor radiosensitivity (P < 0.001). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy in both p53 and Ku70-positive cases for radioresistance were all superior to those of the group positive for p53 alone. In conclusion the examination of the combination of p53 and Ku70 may predict the radiosensitivity of rectal cancer before preoperative irradiation.

Adult↗

Protection of the spinal cord with pentobarbital and hypothermia.

BACKGROUND: Ischemic spinal cord damage during thoracic aortic operations has not been eliminated despite application of various adjuncts. We experimentally investigated the protective effects of pentobarbital and hypothermia on the spinal cord subjected to ischemia. METHODS: Among nine groups of 6 rabbits each, groups AI to AIII underwent 20-minute infrarenal aortic occlusion, and groups BI to BVI underwent 40-minute occlusion. Five milligrams per kilogram of pentobarbital was administered to groups AII and BII; 10 mg/kg in groups AIII, BIII, and BVI; 20 mg/kg in group BIV; and none in groups AI, BI, and BV. In groups BV and BVI, hypothermia was induced. Forty-eight hours postoperatively, the motor function of the lower limbs was evaluated. RESULTS: Statistically significant recovery of motor function was observed in animals in groups AII, AIII, BIII, BIV, BV, and BVI. CONCLUSIONS: Pentobarbital showed dose-dependent protective effects of the spinal cord. Moderate hypothermia alone also showed protective effects. Combined use of pentobarbital and hypothermia resulted in highly significant recovery of spinal cord function.

Animals↗

Mutations of p53 in morphologically non-neoplastic mucosa of long-standing ulcerative colitis.

Two cases of ulcerative colitis (UC)-associated carcinoma or dysplasia and morphologically non-neoplastic mucosa with p53 protein overexpression (MNNM-p53OE) were selected. DNA was extracted from the paraffin blocks of these lesions and exons 5 - 8 of the p53 gene were analyzed by PCR and direct sequencing. In addition, mutations in K-ras codon 12 were analyzed by PCR-RFLP methods. MNNM-p53OE was located surrounding and adjoining a coexisting carcinoma and / or dysplasia. A p53 mutation was detected in 12 / 22 (54.5%) MNNM-p53OE samples, 4 / 8 (50%) dysplasia samples and 8 / 8 (100%) carcinoma samples. The p53 mutations detected in MNNM-p53OE were identical to those demonstrated in the adjoining carcinoma and / or dysplasia. No K-ras codon 12 mutation was detected in any of the samples. These results indicate that MNNM-p53OE may share an identical clonal linkage with a coexisting carcinoma and / or dysplasia, and may be an initial and submorphological form of UC-associated neoplasia. Recognition of MNNM-p53OE in biopsy specimens may help to identify patients with UC at risk of developing colorectal carcinoma.

Adult↗

Heterogeneity of p53 mutational status in intramucosal carcinoma of the colorectum.

The aim of this study was to elucidate whether or not p53 genetic heterogeneity would occur while colorectal carcinoma was limited to the mucosa. Eight cases of endoscopically resected colorectal intramucosal carcinomas were analyzed to determine the p53 gene sequence (exons 5 to 8). Six out of 8 cases showed p53 gene mutations, and in all of them, the mutational status was heterogeneous. In 4 cases, mutated codons were heterogeneous as well. These data indicate that p53 gene alterations in colorectal carcinomas occur and diverge at the stage of intramucosal carcinoma, supporting our previously proposed hypothesis that colorectal carcinomas can be composed of various subclones as regards p53 gene mutation, while the carcinoma is limited to the mucosa, and one of these subclones commences invasion to the submucosa after clonal selection, thus generating a monoclonal invasive carcinoma.

Carcinoma↗

ESR imaging on a solid-tumor-bearing mouse using spin-labeled dextran.

Imaging of a tumor with ESR was tried using two different types of spin probes, a low molecular weight spin probe, CPROXYL, and a polymer spin probe, TEMPO-DX. Spin probes were administered to a mouse bearing a solid tumor that was a transplanted Ehrlich's ascites carcinoma in the back, using two methods, conventional intraperitoneal injection and continuous intravenous injection with a micro-feeder. First, the accumulation of the probe was examined by X-band ESR. CPROXYL, which was administered to a mouse intraperitoneally, was exclusively retained in urine, showing that it was rapidly excreted into the bladder, while TEMPO-DX was absorbed from the peritoneal cavity with difficulty to the vessel. Using continuous intravenous injection, CPROXYL was also rapidly excreted, but it was confirmed that TEMPO-DX concentrated in tumor tissue because it has a long half-life in vivo. In addition, measurement of ESR imaging was done to measure the distribution of spin probes with continuous intravenous injection. The strongest spot of CPROXYL was observed on ESR images, showing the accumulation at the bladder, while the spot of TEMPO-DX was observed in the solid tumor of the back of the mouse. These results suggest that TEMPO-DX could stay much longer than a low molecular weight spin probe in vivo and concentrate at the tumor. TEMPO-DX may be useful for developing specific ESR imaging agents for tumor.

Animals↗

Early colorectal cancer with special reference to the superficial nonpolypoid type from a histopathologic point of view.

The incidence and histopathologic characteristics of nonpolypoid (superficial type) early colorectal carcinomas were studied and compared with those of the polypoid type. The superficial type was subclassified as elevated (type IIa), type IIa with central depression (type IIa + IIc), plain (type IIb), depressed (type IIc), and IIc with marginal elevation (type IIc + IIa). The superficial type comprised 22% and 27% of intramucosal and submucosal carcinomas, respectively. Pure type IIb was not found, and there were only three pure type IIc lesions. Type IIa + IIc and IIc + IIa (and IIc) showed a significantly higher rate of submucosal invasion among the small tumors (59% and 71% less than 20 mm, respectively) compared to the polypoid type; type IIa showed no significant difference. The incidence of lymph node metastasis among submucosal carcinomas showed no significant difference between the superficial type and the polypoid type. About 64% and 52% of type IIa and IIa + IIc tumors accompanied residual adenoma, suggesting that they originated from small, flat adenomas through the adenoma-carcinoma sequence, whereas type IIc + IIa (and IIc) did not have an adenomatous component, implying that they arose de novo or originated through an adenoma-carcinoma sequence at a smaller size than the type IIa and IIa + IIc lesions. Superficial-type early colorectal carcinomas are not rare, and they are not uniform in nature. Rapid growth and invasion to the submucosa is characteristic of superficial-type lesions with a central depression, and only superficial depressed (type IIc + IIa, IIc) lesions can arise de novo. Although they grow rapidly to invade the submucosa, it cannot be said that they show more aggressive behavior than the polypoid type.

Adenocarcinoma↗

[A new cardiovascular surgical instrument: cannula stabilizer].

A new instrument has been developed to safely keep the venous cannula out of the operative field during open heart surgery. This instrument is designed for holding the venous cannula in a curved state at a desired angle. It consists of four semicircular claws mounted on a bar. The size of the claws is tailored so that they comfortably accommodate the standard-size two-stage venous cannula. The bar is flexible enough to be bent manually to form the required curvature, and at the same time it is strong enough to resist the self-uncoiling force of the cannula. When in use, the bar is bent to form the desired curvature and then it is placed on the required portion of the venous cannula. The angle of its curvature and its location on the cannula can be adjusted easily as required during the course of the operative procedure. With this instrument the venous cannula can be easily held in a curved state without disturbing venous return so that the cannula does not come into the way of the surgeon's hands.

Cardiovascular Surgical Procedures↗

Free-floating left atrial ball thrombus early after mitral valve replacement.

A 61-year-old woman was found to have a free-floating ball, thrombus in the left atrium on echocardiographic examination 2 weeks after mitral valve replacement and tricuspid, annuloplasty. The free-floating thrombus was successfully, removed by an open-heart procedure without clinical sequelae. The diagnostic value of routine echocardiography on follow-up of valve surgery is emphasized.

Female↗

Sigmoid colon cancer associated with primary hyperparathyroidism: report of a case.

We present herein a case of sigmoid colon cancer associated with primary hyperparathyroidism (PHP). PHP is known to be associated with malignancy, and decreased intracolonic calcium (Ca) resulting from increased vitamin D (VD) levels may play a role in colorectal carcinogenesis. PHP was diagnosed in this patient by preoperative screening blood chemistry examination. The blood level of intact parathyroid hormone (PTH) was elevated and a parathyroid gland scintigram demonstrated abnormal uptake near the right lower lobe of the thyroid. There was no evidence of bone metastasis, and a sigmoid colectomy was performed with curative intent. The patient had an uneventful postoperative course without a critical elevation of the serum Ca level. This case report suggests that a relationship exists between PHP and colon cancer, and the possible mechanisms of this association are presented in our discussion.

Adenocarcinoma↗

Endovascular stent graft repair of aortopulmonary fistula.

Two patients who had aortopulmonary fistula of postoperative origin with hemoptysis underwent successful repair by means of an endovascular stent graft procedure. One patient had undergone repeated thoracotomies two times, and the other one time to repair anastomotic aneurysms of the descending aorta after surgery for Takayasu's arteritis. A self-expanding stainless steel stent covered with a Dacron graft was inserted into the lesion through the external iliac or femoral artery. The patients recovered well, with no signs of infection or recurrent hemoptysis 8 months after the procedure. Endovascular stent grafting may be a therapeutic option for treating patients with aortopulmonary fistula.

Anastomosis, Surgical↗

Intranasally inoculated Mycoplasma hyorhinis causes eustachitis in pigs.

Specific-pathogen-free pigs were experimentally inoculated with Mycoplasma hyorhinis, Pasteurella multocida, or both bacterial isolates to evaluate the role of these bacteria in the pathogenesis of otitis media. Six pigs were inoculated intranasally with 4.4 X 10(8) colony-forming units (CFU) of M. hyorhinis. Twenty-one days later, three of these six pigs were inoculated intranasally with 5.0 X 10(8) CFU of P. multocida. Three additional pigs were also inoculated intranasally at the time with P. multocida alone. Two pigs served as uninoculated controls. Seven days later, all pigs were euthanatized. Histologically, subacute inflammation was found in 10 auditory tubes of six pigs and two tympanic cavities of two pigs inoculated with M. hyorhinis. Immunohistochemically, M. hyorhinis antigens were detected on the luminal surface of eight of 10 inflamed auditory tubes, and ultrastructural examination confirmed mycoplasmal organisms in two pigs. M. hyorhinis was isolated from the inflamed tympanic cavities of two pigs. None of the pigs inoculated only with P. multocida had otitis, and P. multocida was not isolated from the tympanic cavity. These findings indicate that M. hyorhinis can cause eustachitis but rarely otitis media in specific-pathogen-free pigs.

Administration, Intranasal↗