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Biomedical subjects

S Egawa

Publications and source records attributed to S Egawa.

At least 91 records · Page 5Linked to original sources

A novel somatic mutation in the RET proto-oncogene in familial medullary thyroid carcinoma with a germline codon 768 mutation.

In individuals who carry germline mutations in tumor suppressor genes predisposing them to inherited cancer syndromes, occurrence of somatic mutations in the same genes contributes to tumorigenesis. Germline mutations in the RET proto-oncogene predispose individuals to multiple endocrine neoplasia (MEN) type 2 syndromes. Since these mutations are oncogenic by themselves, somatic mutations in the same gene had been thought unnecessary. Recently, a somatic mutation at codon 918 of RET was reported in medullary thyroid carcinoma (MTC) and C-cell hyperplasia in patients with MEN 2A or familial MTC (FMTC), suggesting its possible contribution to tumorigenesis. We describe here a novel somatic mutation at codon 919 in a patient with FMTC carrying a germline mutation at codon 768 that may also be related to tumor progression.

Aged↗

[A case of fulminant hepatitis caused by antiandrogen, flutamide in a patient with prostate cancer].

Luteinizing hormone-releasing hormone analogue, 3.6 mg goserelin acetate and flutamide, 375 mg per day were used to treat metastatic prostate cancer in a 66-year-old male. Marked increase in serum aminotransferases and total bilirubin levels was noted after 7 weeks of treatment. The enzyme levels returned to normal at 2 months following discontinuation of the treatment. Though incidences of severe hepatotoxicity are rare (0.003-0.18%), cases of flutamide-induced death have been reported. Careful monitoring of patients is mandatory while administering flutamide.

Aged↗

[Intraoperative radiotherapy in carcinoma of the body and tail of the pancreas].

The prognosis for patients with carcinoma of the body and tail of the pancreas is extremely poor. We analyzed the effectiveness of intraoperative radiotherapy (IOR) from the viewpoint of the cumulative survival rate and pain relief. The prognosis of patients who underwent IOR with/without resection was significantly longer than for patients without IOR (p < 0.0001). Better pain relief was obtained by IOR. Although a randomized prospective study is required, resection and IOR will be the central treatment modalities for carcinoma of the body and tail of the pancreas.

Aged↗

Isolation of DNA sequences amplified at chromosome 19q13.1-q13.2 including the AKT2 locus in human pancreatic cancer.

In the human pancreatic cancer cell line PANC1, we detected several DNA fragments with abnormally intensified signals by restriction landmark genomic scanning. Major five of these fragments were cloned. All of the cloned fragments were mapped at the 19q13.1-13.2 region where the AKT2 oncogene was located. Southern blotting using the cloned DNA fragments and a fragment of AKT2 cDNA as probes revealed that the AKT2 gene was amplified in 3 of 12 pancreatic cancer cell lines analyzed including PANC1 and in 3 of 20 primary pancreatic cancers. The AKT2 gene was overexpressed in the 3 cell lines with the amplified gene. The results suggest that the AKT2 gene is a candidate oncogene activated by amplification in some human pancreatic cancers.

Base Sequence↗

Microsatellite instability in transitional cell carcinoma of the urinary tract and its relationship to clinicopathological variables and smoking.

To determine whether microsatellite instability is involved in the development of transitional cell carcinoma (TCC) of the urinary tract, a microsatellite instability assay was carried out using PCR with 9 microsatellite loci. Thirty-eight TCC samples (30 patients with bladder cancer, 5 with renal pelvic tumors and 3 with ureteral tumors) and 1 lymph node with metastasis were examined. Microsatellite instability was found in 8 of 38 tumors examined, and 3 showed alterations in more than 2 microsatellite loci. All 8 tumors were beyond grade 2 and stage pT2 advanced tumors. Stages pT1-2 and pT3-4 patients differed significantly. Microsatellite instability was greater in smokers than non-smokers, but the differences were not significant. Microsatellite instability in TCC of the urinary tract is rare in superficial tumors but more common in invasive tumors. Microsatellite alterations would thus appear to occur, and possibly be importantly involved, in the tumorigenesis of urinary tract TCC.

Carcinoma, Transitional Cell↗

Risk of progression and dying of clinically localized prostate cancer in Japan.

Study was made of the conservative management of 107 men with clinically localized prostate cancer. Distant metastasis developed more frequently in patients with poorly differentiated tumors than in those with well- and moderately differentiated counterparts (P < 0.01). Poorly differentiated histology was strongly associated with cancer-specific death (P < 0.01). The progression-free and cancer-specific survival of patients with stage T1a disease was significantly better than that of patients with stages T1b, T2a-b, and T2c tumors (P < 0.05). Available data clearly demonstrate that prostate cancer is a progressive disease when managed conservatively. Long-term follow-up data indicate the natural history of prostate cancer not to differ significantly according to race, despite noteworthy differences in prevalence and mortality. Patients with localized prostate cancer would be candidates for expectant therapy if they had lower-grade tumors and a life expectancy of 10 years or less. For patients with a 10-year or greater life expectancy and any grade of disease definitive therapy should be applicable.

Aged↗

Deoxyribonucleic acid ploidy status as no basis for pathologic stage prediction in clinically resectable prostate cancer.

OBJECTIVES: Assessment of deoxyribonucleic acid (DNA) ploidy status of a tumor as a means for predicting pathologic stages in prostate cancer. METHODS: DNA ploidy of each focus of a cancer in 70 radical prostatectomy specimens was determined by nuclear image analysis. DNA ploidy was compared with the pathologic features of tumors. RESULTS: One hundred three individual cancers in 70 patients were used for DNA ploidy analysis. Of these, 39 (38%) were diploid and 64 (62%), nondiploid. DNA ploidy was weakly correlated with increase in tumor volume (P = 0.049) but not tumor grade. The relationship between DNA content and extraprostatic spread was not statistically significant. Increase in tumor volume and grade promoted extraprostatic spread more than nondiploidy, as shown by multivariate analysis. CONCLUSIONS: The incidence of a nondiploid cell population in a tumor focus in prostate cancer is essentially the same, at least for Americans and Japanese. DNA ploidy of a tumor cannot serve as a means of pathologic stage prediction in clinically resectable prostate cancers, contrary to many previous studies. Thus, DNA content analysis would be of no use for deciding on the treatment strategy of prostate cancer.

DNA, Neoplasm↗

Significance of preoperative parameters for predicting tumor volume in nonpalpable prostate cancer.

Preoperative parameters were assessed for their usefulness in predicting tumor volume in 26 cases of nonpalpable prostate cancer. The number of positive biopsy cores was found to be the parameter which predicted most accurately tumor volume in surgical specimens. All 14 patients with multiple positive cores had an index tumor of 0.5 cm3 or more in radical prostatectomy specimens. Only six tumors with a single positive core were substantial. Three of the patients showed a serum level of prostate specific antigen (PSA) of 4.0 ng/ml or more. The pathological stage and prostatectomy Gleason sum could not be predicted accurately by this variable (P>0.05). To predict index tumor volumes of 1.0 cm3 or greater, stepwise logistic regression analysis was conducted, and on the basis of the results it was possible to single out multiple positive biopsies as the only significant variable. The number of positive biopsies appeared reliable for predicting tumor volume of surgical specimens in cases of nonpalpable disease. The presence of significant tumors despite "normal" levels of PSA warrants further investigation of variables that can predict such prostate cancers. An adequate model for predicting significant tumors in oriental male populations should be established using samples of larger size.

Biopsy, Needle↗

Preoperative serum prostate-specific antigen, clinical stage and Gleason sum as basis for predicting final pathological stage in Japanese patients with prostate cancer.

By logistic regression analysis and log-likelihood ratio chi-square test, the usefulness of preoperative variables (prostate specific antigen [PSA], clinical stage and biopsy Gleason sum) for predicting the final pathological stage was assessed in 77 patients with clinically resectable prostate cancers. Pathologically, 32 (41.6%) had organ-confined disease. Extracapsular extension was found in 41 (53.2%), seminal vesicle involvement in 30 (39.0%), positive pelvic lymph nodes in 10 (13.0%) and a positive surgical margin in 27 (35.1%). Each preoperative variable was found to be significantly associated with the final pathological stage. Any combination of these variables was more predictive for extraprostatic disease, compared with each individual variable. Extraprostatic spread was found more frequently in patients with lower serum PSA in this Japanese elderly male population compared with North American males. These preoperative variables considered in combination may provide valuable information for management decisions related to prostate cancer. Serum PSA alone cannot reliably predict pathological stage on an individual basis except in patients with a PSA level of 20 ng/ml or greater. The high incidence of extraprostatic spread at intermediate PSA underscores the importance of selecting an ideal cutoff value for PSA-based screening in a Japanese male population.

Aged↗

A non-randomized comparative study of visual laser ablation and transurethral resection of the prostate in benign prostatic hyperplasia.

BACKGROUND: Transurethral resection of the prostate (TURP) has been the preferred surgical treatment for benign prostatic hyperplasia (BPH) for the past 50 years. Alternative methods for treating BPH such as visual laser ablation (VLAP) have been established during the past decade. In order to assess the safety and efficacy of VLAP, this alternative method was performed using a Urolase fiber and neodymium: yttrium-aluminum-garnet laser, and compared to results obtained in patients treated with TURP for BPH. METHODS: In this non-randomized comparative study, 100 BPH patients were equally split between treatment with VLAP or TURP, and their cases compared. The efficacy was assessed using an International Prostate Symptom Score, urinary flow rates, post-void residual urinary volume and an estimated prostate volume. RESULTS: There was a clinically significant improvement in all parameters in both groups. In the VLAP and TURP groups, 92.0% and 81.6%, 90.2% and 86.2 and 93.1% and 100.0% were categorized as effectively-treated cases at 3, 6 and 12 months post-operatively, respectively. No severe side effect was seen in VLAP group. The total and post-operative lengths of hospitalization in the VLAP group were shorter, but the duration of post-operative bladder irrigation was longer in these patients. CONCLUSIONS: Although TURP remains the standard surgical treatment for BPH, VLAP is associated with less morbidity and the clinical outcome is similar compared to patients treated with TURP. VLAP in conjunction with TURP may result in less risk of postoperative urinary retention and vesical irritability.

Aged↗

Giant retroperitoneal cyst in an adult male.

This paper presents a case of a symptomatic giant retroperitoneal cyst in an adult male. The unilocular cyst was excised successfully with resolution of the attendant symptoms. Histological findings of the cyst wall suggested a lymphangiomatous etiology. Any good risk patient found to harbor such a cyst should undergo complete excision in view of the potential for the development of symptoms and complications.

Cysts↗

[Renal cell carcinoma associated with circumferential "ring-like" calcification].

A 37-year-old man was found to have large calcification in the left kidney in a health check. This calcification has not changed in size during 3 years with computerized tomographic (CT) studies. However, a suspicious lesion for a malignant tumor with the calcification was suggested by a magnetic resonance image (MRI) study. Thus, the patient underwent tumor enucleation and the histology showed the mixed typed renal cell carcinoma. Although it remains controversial, partial nephrectomy or tumor enucleation would be considered in a case of renal cell carcinoma with calcification, which is usually considered to have a favorable prognosis compared to that of a tumor without a calcification.

Adult↗

[Renal cell carcinoma in childhood: a case report].

A case of renal cell carcinoma (RCC) in a teenage patient is reported. A 13-year-old girl visited our hospital with the complaint of dyspnea and right abdominal mass. CT scan and chest X-P revealed a right renal tumor with multiple lung metastasis. Wilms' tumor was suspected and a combination chemotherapy consisting of actinomycin D and vincristin was performed. Since the tumor was insensitive to these agents, open biopsy was done. The pathological findings showed clear cell renal cell carcinoma. Despite the administration of alpha interferon, 5-FU and cimetidine, the disease was progressive and the patient died 5 months after diagnosis. It is important to consider the possibility of renal cell carcinoma in teenage patients with a renal mass, since more than 40% of the renal tumors in this age group are renal cell carcinomas.

Adolescent↗

Inhibition of lymphatic metastasis in a syngeneic rat fibrosarcoma model by an angiogenesis inhibitor, AGM-1470.

We examined whether lymphatic metastasis was inhibited by the potent angiogenesis inhibitor AGM-1470 [O-(chloroacetyl-carbamoyl)fumagillol, TNP-470] using a rat lymphatic metastasis model. Clone A of the rat fibrosarcoma AS653HM, when inoculated into the footpads of syngeneic rats, highly and preferentially metastasized to lymph nodes. In contrast, when AGM-1470 was administered subcutaneously to rats bearing the tumor cells, the tumor growth and incidence of metastasis in the lymph nodes were reduced in a dose- and schedule-dependent manner. Similar inhibition of lymphatic metastasis was also observed in the rats in which treatment with AGM-1470 was initiated following resection of the primary tumor in the foot, indicating that the treatment with AGM-1470 inhibited the progression of lymphatic metastasis at the metastatic sites of the lymph nodes. These results suggest that AGM-1470 can be a potential agent to prevent lymphatic metastasis.

Animals↗

Early detection of prostate cancer. Results of a prostate specific antigen-based detection program in Japan.

BACKGROUND: Prostate cancer increasingly is becoming a medical problem in Japan. To maximize the chance for cure, extensive effort is being made to detect prostate cancer while confined to the gland. METHODS: Determination was made of serum prostate specific antigen (PSA) in the early detection of prostate cancer in an Asian male population aged 55 years or older. Recommendation for biopsy was based solely on this parameter when its value exceeded 2.0 ng/ml in IMx immunoenzymetric assay. RESULTS: Of 1189 men, 150 (12.6%) had elevated values. The proportion of males with serum PSA greater than 4.0 ng/ml was only 3.4%. Of the 99 males who underwent ultrasound-guided biopsies, 16 cancers were detected, a cancer detection rate of 1.3%. Most of these (81.3%) were clinically localized cancers. Seven patients with cancer had serum PSA levels below 4.0 ng/ml including 5 less than 3.0 ng/ml. These tumors would have been overlooked if the conventional cutoff levels of 4.0 ng/ml had been applied. Radical prostatectomy was conducted on 13 patients. All had histologic features of clinically significant cancer and 69.2% were pathologically confined within the gland. CONCLUSIONS: Elderly Asian males appear to have lower serum PSA than their Western counterparts. The optimal cutoff of serum PSA for early detection should be examined further in Asian male populations. Differences in the incidence of prostate cancer between ethnic groups may have been overestimated in previous studies owing in part to unawareness by the physician and general public. Though the frequent use of more sophisticated diagnostic modalities will likely disclose greater numbers of prostate cancers in Japan, whether early detection reduces mortality by minimizing risk of death from cancer remains a point to be determined.

Aged↗

Genomic instability of microsatellite repeats in prostate cancer: relationship to clinicopathological variables.

Sixty-six patients with prostatic adenocarcinoma were screened for somatic instability at 8 microsatellite marker loci on 5 chromosomes. Differences in unrelated microsatellites for tumor and normal DNA were detected in 13 (19.7%) patients. Only extraglandular spread (nodal involvement and distant metastasis) was found to show significant association with somatic instability after controlling for other clinicopathological variables (P < 0.05). Microsatellite instability may possibly occur during the early stages of neoplastic transformation in a subset of prostate cancer rather than as a late event. This may be related to a phenotype with growth advantage. The frequency of this mutator phenotype is much higher in the United States than Japan, reflecting racial differences in the molecular tumorigenesis of this malignancy.

Adenocarcinoma↗