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HIV infection, in particular in patients with developing AIDS, carries a risk of causing toxoplasmosis with encephalitis, which is mostly caused by a form (bradyzoite) of the protozoan parasite Toxoplasma gondii. HIV/AIDS in Japan has been recognized as a serious health issue in recent years. In this study, to elucidate T. gondii seroprevalence in HIV-positive patients in Japan and associated characteristics with Toxoplasma parasite infection, the titer of T. gondii IgG (Tg-IgG) was measured in 399 HIV-positive patients who visited a hospital in Tokyo, Japan, between 2015 and 2017. A questionnaire survey was also conducted to investigate associations between lifestyle and customs. As a result, the overall prevalence of Tg-IgG-positive serum was 8.27% (33 cases of 399). All the cases positive for Tg-IgG were confirmed using the Sabin-Feldman dye test; the titers between each examination correlated robustly (p 0.001, r = 0.6). A correlation between Toxoplasma infection rate and age was determined (p 0.001), whereas there was no significant correlation with lifestyle customs such as consuming undercooked meat or owning a cat. An association between Toxoplasma infection and experience of dwelling in the Hokkaido area, the northern part of Japan, was observed (p = 0.001). These results suggested that the proportion of those who were previously exposed to Toxoplasma parasites in the HIV-positive population has been maintained at a similar level as that of the HIV-negative population in Japan, providing clear information about the potential risk of toxoplasmic encephalitis.

OBJECTIVES: This study was conducted to clarify the rate of late diagnosis of HIV infection and to identify relationships between the reasons for HIV testing and a late diagnosis. METHODS: This retrospective cohort study was conducted among HIV-positive patients at the Jikei University Hospital between 2001 and 2014. Patient characteristics from medical records, including age, sex, sexuality, the reason for HIV testing and the number of CD4-positive lymphocytes at HIV diagnosis, were assessed. RESULTS: A total of 459 patients (men, n=437; 95.2%) were included in this study and the median age at HIV diagnosis was 36 years (range, 18-71 years). Late (CD4 cell count

Malaria is one of the most common and serious infectious diseases in the tropics and subtropics. For high-risk travelers to endemic regions, malaria chemoprophylaxis is recommended. Internationally, atovaquone-proguanil (A/P), mefloquine (MEF), or doxycycline (DOX) are the prescribed malaria chemoprophylactic drugs. However, A/P and DOX are not approved in Japan. Therefore, the data on A/P for malaria chemoprophylaxis in Japanese travelers are not clear. We analyzed questionnaire survey data obtained in Hibiya Clinic to assess the safety and tolerability of A/P and compare them with those of MEF for non-immune Japanese travelers. A/P was given to 278 travelers and MEF to 38 travelers. The mean duration of each prophylaxis is for 20.0 ± 9.6 and 59.0 ± 15.9 days, respectively. Nine travelers discontinued prophylaxis: 5 in the A/P prescribed group (A/P group) and 4 in the MEF prescribed group (MEF group), and the rate of discontinuation was significantly less in the A/P group. The frequency of adverse events was significantly less in the A/P group than in the MEF group [52 cases (18.8 %) vs. 14 cases (36.8 %), respectively]. In particular, the frequency of psychoneurotic adverse events was significantly less in the A/P group. These results suggest that A/P is better tolerated and has fewer adverse events than MEF in non-immune Japanese travelers.

We gathered data regarding age, sex, and positivity rates for human immunodeficiency virus (HIV), syphilis, gonococcus, and chlamydia from individuals who underwent free and anonymous sexually transmitted infection (STI) testing conducted at the Jikei University School of Medicine Hospital (our hospital). These data were compared to results of subjects who underwent similar testing at the Minato Health Center and several private facilities of urologists and gynecologists belonging to the Minato Ward Medical Association. The positivity rate of chlamydia was found to be high in female subjects, particularly at the Minato Health Center, with 15 of 194 subjects (7.73 %) testing positive. In our hospital, we only detected 3 of 133 subjects (2.26 %) who were gonococcus positive. On the other hand, at the doctor's facilities, 10 of 188 male subjects (5.32 %) were syphilis positive, and 8 of 185 male subjects (4.32 %) were chlamydia positive, thus showing high positivity rates for both infections. At our hospital, 1 of 231 subjects was positive for gonococcus and 4 of 230 subjects (1.74 %) were positive for chlamydia, thus showing lower positivity rates for both infections. HIV-positive subjects were, however, only confirmed at our hospital, with 2 of 243 subjects (0.82 %) being positive. We were able to diagnose infected patients using free and anonymous STI testing at hospitals, and the same as at doctors' facilities. This result suggests that the hospitals that have many opportunities to diagnose HIV patients may become potential candidates for the development of new consultation facilities, establishment of testing facilities, and enhancement of consultation processes that include STI prevention.

We report a case of meningococcemia without meningitis, which is a rare infectious disease in Japan. A 32-year-old woman was referred to our hospital with fever and joint pain. Her clinical presentation and the results of laboratory examination on admission suggested viral infection. However, her condition rapidly progressed to septic shock with fulminans purpura. Blood culture grew Neisseria meningitidis. She received antimicrobial therapy and underwent localized therapy for skin lesions. Meningococcal infection should be considered in patients who have fever along with skin rash or petechiae even when there are no signs of meningitis. In this report, we also review case reports of meningococcemia without meningitis in Japan.

Bone marrow-derived cells (BMDC) play crucial roles in tissue regeneration. Granulocyte-colony stimulating factor (G-CSF) mobilizes BMDC and may facilitate the repair of kidney tissues after ischemia/reperfusion (I/R) injury. The tissue protective action of resveratrol, an antioxidant, might modify the regenerating potential of BMDC in I/R renal injury. This study examined whether G-CSF and/or resveratrol affect the recruitment of BMDC into vascular endothelial cells and renal tubular cells and the kidney function after I/R injury. I/R renal injury was induced in female mice that had been lethally irradiated and transplanted with male bone marrow cells. The mice were given saline, resveratrol or G-CSF, daily for 7 days. Non-irradiated and non-bone-marrow-transplanted female mice, which underwent the same kidney injury, were included as control. White blood cell (WBC) count and serum creatinine were monitored. Immunohistologic evaluation for renal tubular cells (cytokeratin) and endothelial cells (factor VIII-related antigen), and fluorescence in situ hybridization for mouse Y chromosome were performed. Although WBC was significantly higher in the G-CSF group, there was no significant difference in creatinine levels among all groups. Factor VIII-related antigen-positive cells with a Y-chromosome signal were identified in the capillary wall between renal tubuli and most frequently seen in the G-CSF group (p < 0.0001). Resveratrol did not affect kidney recovery in this model. No cytokeratin-positive renal tubular cells having a Y-chromosome signal were identified. In conclusion, BMDC are recruited into endothelial cell in I/R renal injury without apparent renal tubular cell regeneration, and G-CSF facilitates the endothelial cell regeneration.

We report a case of small cell lung cancer in a patient with human immunodeficiency virus (HIV) infection. The patient was a 51-year-old man diagnosed 8 years previously as seropositive for HIV, who was admitted to our hospital for re-evaluation of antiretroviral medications due to multidrug resistance. Chest radiograph revealed an abnormal hilar shadow subsequently confirmed to be small cell lung cancer. He received chemotherapy concurrently with highly active antiretroviral therapy (HAART), and lived for 14 months after the diagnosis. The prognosis of lung cancer in HIV-seropositive patients is very poor, and adverse effects of chemotherapy occur more frequently than in other patients. However, the simultaneous antiretroviral agents and combination chemotherapy was successful. Such treatment may be effective despite an otherwise poor prognosis, including HIV infection.

Background: We report a rare case of acute eosinophilic pneumonia (AEP) associated with heated rubber fume exposure. Methods: A 31-year-old Ethiopian man, working at a rubber plant, was admitted to our hospital because of refractory dyspnea and fever. Computed tomography of the chest showed bilateral interstitial shadows and pleural effusion. We suspected AEP and performed fiberoptic bronchoscopy. Results: The eosinophil fraction was elevated at 59% in the bronchoalveolar lavage fluid (BALF). From the history of inhalation of heated rubber at the working place and hypereosinophilic counts in the BALF, he was given a diagnosis of AEP associated with heated rubber fume exposure. His symptoms and chest radiographic findings were drastically improved by corticosteroid therapy. Conclusions: Heated rubber fume can be a causative substance for AEP. In similar situations, physicians should consider AEP and order various examinations for confirmation.

2004年9月から11月にかけて日本海側北部を中心に, 原因不明の急性脳炎 (脳症) が多発した. 多くの患者は末期腎障害があり, スギヒラタケを摂取していたという共通事項があった. 秋田県では23例の届け出があった. 23例中16例は慢性透析患者であり, 血液透析患者であることとスギヒラタケ摂取が共通事項であることを私たちは報告してきた. 本研究は透析患者における急性脳症発症の危険因子を明らかにするため, 急性脳症発症例と非発症例の臨床背景やスギヒラタケ摂取の有無を比較検討した. 16名の急性脳症患者と秋田県内在住1,674名の脳症非発症透析患者について透析施設に質問用紙を郵送した. 16名の脳症患者と1,236名 (非脳症例中の73.8%) の非発症透析患者, 計1,252名から回答を得た. 16名の急性脳症例のうち, スギヒラタケ摂取が明らかであったのは14名, 不明は2名であった, 1,252名の透析患者中573名 (45.8%) がスギヒラタケを摂取し, 573名中14例 (2.4%) が急性脳症となった. 急性脳症16例のうち6例 (37.5%) が死亡した. 明らかにスギヒラタケを摂取していない患者で, 急性脳症を発症した例はなかった. 急性脳症発症例と非発症例を比較すると, 年齢, 性, 透析期間, 透析法に差はなかった. 単変量解析では, 糖尿病 (p=0.040, オッズ比3.10) とスギヒラタケ摂取者 (p=0.010, オッズ比8.63) の頻度が急性脳症発症例に多かった. 本研究結果からスギヒラタケ摂取は急性脳症発症の重要な危険因子であることが示唆された. スギヒラタケが含有していると考えられる原因物質解明のため, さらなる検討が必要である.

2004年9月から11月にかけて新潟, 山形や秋田を中心に, 原因不明の急性脳炎 (脳症) が多発した. 多くの患者は末期腎障害があり, スギヒラタケを摂取していたという共通事項があった. 秋田県では24例の届け出があった. 24例中17例は慢性透析患者であり, 3例は保存期腎不全であった. 本研究は17例の脳症発症透析患者において, 何らかの共通した臨床背景や透析条件が急性脳症発症に影響しているかを検討した. その結果, 平均年齢64.2歳, 平均透析期間56.8か月, 男性9女性8, 腎不全の主たる原因疾患は糖尿病性腎症と慢性腎炎であった. 17例の共通事項は, 血液透析患者であることとスギヒラタケ摂取だけであった. 服用薬剤, 透析液, 抗凝固剤や透析膜に特徴的なものはなかった. さらに, 2施設102名の透析患者を調査し, スギヒラタケ摂取率と急性脳症発症率を検討した. 102名中57名 (55.8%) がスギヒラタケを摂取し, 57名中5例 (8.7%) が急性脳症を発症, 5例中2例 (40.0%) が急性脳症によって死亡した. 本調査では血液透析とスギヒラタケ摂取以外に, 他に共通した臨床背景や透析条件は見い出すことができなかった. 原因究明のためのさらなる検討が必要である.

BACKGROUND A body-weight-based dose of tacrolimus often results in marked individual diversity of blood drug concentration. Tacrolimus is a substrate for cytochrome P450 (CYP) 3A5 and p-glycoprotein encoded by CYP3A5 and MDR1 (ABCB1), respectively, having multiple single nucleotide polymorphisms. In this study, we genotyped CYP3A5 A6986G, MDR1 G2677(A/T), and C3435T polymorphisms and investigated the association between these polymorphisms and the pharmacokinetics of tacrolimus in renal transplant recipients. METHODS Thirty consecutive recipients were enrolled in this study. The pharmacokinetics of tacrolimus was analyzed on day 28 after transplant, when the daily dose was adjusted to the target trough level of 10-15 ng/mL. The polymerase chain reaction-restriction fragment length polymorphism and direct sequence method were used for genotyping the CYP3A5 and MDR1 polymorphisms, respectively. RESULTS The single tacrolimus dose per body weight was significantly higher in CYP3A5 *1 carriers than CYP3A5 *3/*3 carriers (0.143+/-0.050 vs. 0.078+/-0.031 mg/kg, P

Background: The influence of dialysis modality on the acute rejection (AR) rate after renal transplantation is controversial. We investigated whether the pretransplant dialysis modality correlated with the lymphocyte subset populations and the incidence of AR after renal transplantation. Methods: Thirty-eight first living renal transplant recipients, consisting of 22 patients on pretransplant hemodialysis (HD) and 16 patients on pretransplant peritoneal dialysis (PD), were studied. Peripheral blood samples were taken on days -1 through 28 after transplantation, and the lymphocyte fractions were exposed to the monoclonal antibodies anti-CD3, CD19, CD4, CD8 and CD28 for a flow cytometer analysis. Biopsy specimens were obtained at the time of presumed AR episodes and on day 28 after transplantation. Results: The PD patients had a higher frequency of AR (37.5% in PD vs 9.1% in HD patients, P = 0.034). In contrast, two HD patients showed graft loss at 18 and 30 months after transplantation. The increases of CD3, CD19, CD4 and CD4+ CD28+ cells in the PD patients occurred earlier than in the HD patients and the numbers of these cells in the PD group were higher than those in the HD between days 3–28 after transplantation, most significantly on day 7. Conclusions: These findings suggest that the PD patients with similar clinical characteristics could potentially have a higher immunocompetence and immune responsiveness associated with a higher rate of AR in the early stage of renal transplantation when compared with the HD patients.

Objectives To elucidate the clinical significance of the HER-2 gene alterations in urine-exfoliated cells detected by fluorescence in situ hybridization (FISH) in patients with urothelial transitional cell carcinoma. Methods The relative increase of HER-2 (RI-HER2) and gain of chromosome 17 (G-17) in urine-exfoliated cells were examined using DNA probes for HER-2 and the chromosome 17 centromere in 103 patients. In addition, FISH analysis was performed using corresponding paraffin-embedded tissue sections from 45 cases to compare the results obtained using urine-exfoliated cells and those obtained using paraffin-embedded tissue. Results RI-HER2 and G-17 was found in 23 (22.3%) and 46 (44.6%) of 103 patients, respectively. RI-HER2 was significantly more frequent in tumors with two or more recurrences (40.7% versus 15.8%, P = 0.010) and in those with carcinoma in situ (CIS) (35.4% versus 15.9%, P = 0.029). G-17 was more frequent in high-grade tumors (69.1% versus 16.7%, P = 0.032), invasive tumors (63.6% versus 14.3%, P < 0.001), and in patients with CIS (77.1% versus 29.0%, P < 0.001). The positive rate for FISH (presence of RI-HER2 and/or presence of G-17) tended to be more frequent in FISH than in cytology. A comparison of the analyses using urine-exfoliated cells and paraffin-embedded tissue showed identical results in 36 (80.0%) of 45 cases. Conclusions Numeric alterations of the chromosome 17 centromere in urine-exfoliated cells detected by FISH may reflect the malignant potential of urothelial carcinoma. In addition, a relative increase in HER-2 was associated with the number of recurrences and the presence of CIS.

Objectives To report our technique and early results of hand-assisted retroperitoneoscopic nephrectomy (HARN) for living donor transplantation and to assess its feasibility. Methods HARN was effectively and safely performed on 44 donors from July 2001 to September 2003 at Akita University Medical Center. We describe our techniques and experiences with HARN and compare the early results with those of 27 cases of open donor nephrectomy at our institution. Results The mean operating time was 260 minutes (range 173 to 445), the mean estimated blood loss was 249 mL (range 15 to 967), and the mean warm ischemia time was 2.2 minutes (range 0.8 to 6.4). These parameters were similar to those of open donor nephrectomy. Intraoperative and postoperative complications occurred in 1 (2.3%) and 2 (4.6%) cases, respectively, but they were all minor. HARN was converted to open nephrectomy in 1 case (2.3%) because of uncontrollable bleeding. All HARN donors were ambulant within 2 days postoperatively and could initiate oral intake on the first postoperative day. Regarding graft function, 41 recipients (93.2%) had an immediate onset of diuresis and 3 (6.8%) had delayed renal function. The serum creatinine 7 days and 1 month postoperatively was not significantly different between the HARN group and the open nephrectomy group. Conclusions HARN for living donors is one excellent option for donor nephrectomy because the procedure does not require intraperitoneal manipulation, thus reducing the risk of abdominal visceral injury, and also because of the minimal warm ischemia time owing to rapid extraction of the kidney with hand assistance.

The glutathione peroxidase 1 gene (GPX1) and the manganese superoxide dismutase gene (MnSOD) encode the main antioxidant enzymes that detoxify endogenous reactive oxygen species involved in carcinogenesis. Polymorphisms of GPX1 and MnSOD genes, and the risk of transitional cell cancer of the bladder were tested.Genotypes of the leucine (Leu) to proline (Pro) polymorphism at codon 198 of GPX1, the alanine (Ala) to Valine (Val) polymorphism in exon 2 and the isoleucine to threonine polymorphism at codon 56 of MnSOD were determined by a polymerase chain reaction-restriction fragment length polymorphism technique in 213 patients and 209 normal controls.There was a significant difference in GPX1 genotype frequency between the case and control groups (p = 0.001). The adjusted OR for bladder cancer was 2.63 for the Pro/Leu genotype compared with the Pro/Pro genotype (95% CI 1.45 to 4.75, p = 0.001). Compared with the Pro/Pro genotype the Pro/Leu genotype was significantly associated with advanced tumor stage (Ta-1 vs T2-4, OR 2.58, 95% CI 1.07 to 6.18, p = 0.034) but not with tumor grade. Analysis of the MnSOD polymorphism provided no significant results. However, in men with at least 1 Ala MnSOD allele the risk associated with the Pro/Leu GPX1 genotype increased up to 6.31 (95% CI 1.28 to 31.24, p = 0.024).The GPX1 Pro/Leu genotype may significantly increase the risk of bladder cancer and the increased risk may be modified by the Ala-9Val MnSOD polymorphism. The GPX1 genotype may further affect the disease status of bladder cancer.

Aim: Microalbuminuria is typically observed in renal transplant recipients with systemic hypertension. The effects of angiotensin II type 1 receptor antagonist (losartan) on the hypertensive recipients have been evaluated. However, the clinical background of normotensive recipients with microalbuminuria and the effect of losartan administration in those subjects have not been clarified. One of the two purposes for the present study was to investigate the clinical characteristics of normotensive recipients with microalbuminuria. The other was to evaluate the effect of losartan on urinary excretion of albumin in these patients. Methods: The clinical data and the change of the single kidney glomerular filtration rate (GFR) for the graft by radionuclide study were assessed in 13 normotensive recipients with microalbuminuria. These were compared with the data of 13 normotensive patients without microalbuminuria. The 13 recipients with microalbuminuria were treated with losartan for one year and urine excretion of albumin, N-acetyl-β-D-glucosaminidase (NAG) and serum creatinine (S-Cr) levels were measured. Results: The GFR of the grafts from donors to recipients significantly increased (30.9 to 55.2 mL/min) in microalbuminuric recipients, but did not significantly increase in the non-microalbuminuric recipients. Decreases of the urinary excretion rate of albumin (351 ± 261 at baseline to 158 ± 14 mg/gCr at 12 months), NAG (13 ± 5 to 10 ± 3 IU/gCr) and S-Cr (1.7 ± 0.6 to 1.5 ± 0.4 mg/dL) were observed in the microalbuminuric recipients with losartan administration. Conclusions: The present study suggests that an increased single kidney GFR of the graft from the donor in situ to the recipient might be a cause of microalbuminuria in normotensive recipients. The one-year effects of losartan were observed in terms of the decrease in urinary excretion of albumin, NAG and S-Cr levels.

Background: We previously reported that the ileocecal rectal bladder consists of interposition of an intussuscepted ileocecal segment between the ureters and the rectum for those in whom the urethra is not available. Although the ileocecal rectal bladder has been well accepted by most patients, it requires an extensive preparation along the ascending colon. We present a modified operation technique (rectosigmoidal bladder) by using the ileal segment alone as an interposing antireflux component and by using the sigmoidal segment to augment the rectal capacity. Methods: From February 1993 to July 2002, 30 patients with a median age of 64 years underwent construction of a rectosigmoidal bladder. Median follow-up period was 26 months (range, 13–125). The follow up was carried out using clinical and functional assessments such as evacuation status, serum chemistry and radiographic evaluation of the upper urinary tracts and rectosigmoidal pouch. To assess the postoperative health-related quality of life, we carried out a survey comparison of the ileocecal rectal bladder patients and the rectosigmoidal bladder patients. Results: No operative or urinary diversion-related postoperative mortality was encountered. All rectosigmoidal bladders had sufficient capacity, with no evidence of urinary reflux or daytime incontinence. When compared with our previous procedure, the ileocecal rectal bladder, the present procedure had advantages with respect to complications with urine-fecal leak and acidosis. There were no differences in mean operation time, or in the health-related quality of life survey, between the two procedures. Conclusions: Our experience showed that this technique should be considered for those in whom the urethra is not available.

A 28-year-old man, who had undergone right orchiectomy and prophylactic irradiation for stage I seminoma 6 years ago, developed left testicular tumor. Since the secondary tumor was localized in the lower pole of the testis, partial orchiectomy was performed with an attempt to preserve the testicular function. The pathological finding of the surgical specimen was a mixed type testicular tumor consisting of seminoma, embryonal carcinoma and teratoma elements. Postoperative chemotherapy with 3 courses of BEP regimen resulted in azoospermia, but the impaired spermatogenesis recovered to a normal range within 18 months with no evidence of tumor recurrence and his wife delivered a healthy baby 2 years later. For the synchronous or metachronous bilateral testicular tumors, the combination of organ sparing surgery and chemotherapy could be a treatment of choice.

A novel surgical technique of antireflux with an ileal conduit for urinary diversion is presented with our early results. The mid 8-cm portion of an isolated terminal ileum is intussuscepted. After skeletonization of the mesenterial vasculature, 3 rows of 4 mattress seromuscular silk sutures are placed on the ileum. By tying the sutures successively, the ileum is intussuscepted and the resultant nipple is secured simultaneously between its outer and inner layers. The outer nipple layer and the recipient ileal layer are further fixed as a whole by placing 3 rows of metal staples. The nipple base is secured by interrupted silk sutures and the mesenterial defect is closed. This technique was applied to 30 patients undergoing rectosigmoidal bladder procedure, a modified ileocecal rectal bladder, in which the antireflux conduit was interposed between the ureters and the rectosigmoidal pouch. Ureteral reflux was observed in none of the patients during a mean follow-up period of 29.9 months. Of the 60 renal units, 53 (88.3%) had normal pyelography and 7 (12.7%) showed mild hydronephrosis at 3–6 months postoperatively. This antireflux technique is simple and reliable, and can be applied to other urinary diversion/reconstruction surgeries, such as the continent reservoir, orthotopic neobladder, and/or bladder augmentation.

It is widely recognized that androgen biosynthesis and metabolism are associated with the development and progression of prostate cancer. The human CYP11A1 gene (CYP11A1) encodes the P450scc enzyme, which mediates the first step in sex steroid hormone synthesis. The gene contains a (tttta)n-5 bp tandem repeat microsatellite polymorphism located at 528 bp upstream of the translation initiation site and the CYP11A1 mRNA level may be modulated by the polymorphism. Recent studies suggested that the absence of the shortest (tttta)4 allele of the CYP11A1 polymorphism was associated with a risk of polycystic ovary syndrome and with a hyperandrogenic state in polycystic ovary syndrome patients. In our study which included 278 prostate cancer patients, 213 benign prostatic hyperplasia (BPH) patients and 299 male controls, we explored the association between the CYP11A1 polymorphism and prostate cancer on the hypothesis that the presence of the (tttta)4 allele may increase the risk of the development or progression of prostate cancer. In addition, we measured the serum levels of 6 steroid hormones or their metabolite (i.e., testosterone, free-testosterone, estrone, estradiol, dehydroepiandrosterone and androstendione) in 156 control males subjects and compared those with and without the (tttta)4 allele. The polymorphism was evaluated by PCR amplification of a 145–170 bp fragment followed by polyacrylamid gel electrophoresis. The CYP11A1 allele consisted of 4, 6, 7, 8 and 9 (tttta)-5 bp repeats. There was no significant difference in the genotype frequency as for the presence of the (tttta)4 allele between prostate cancer patients and male controls, and between prostate cancer patients and BPH patients. However, there was a significant difference in the genotype frequency in relation to the disease status. Prostate cancer patients without the (tttta)4 allele had an increased risk of metastatic disease (stage D) compared to those with the (tttta)4 allele [adjusted odds ratio (aOR)=1.76, 95% confidence interval (Cl)=1.07–2.90 and p =0.026]. Patients without the (tttta)4 allele had an increased risk of high grade prostate cancer (Gleason score 8 or more, or poorly differentiated cancer) compared to those with the (tttta)4 allele (aOR=1.79, 95% Cl=1.08–2.97 and p =0.025). No significant difference in the serum levels of 6 steroid hormones or their metabolites was found in the presence or absence of the (tttta)4 allele. Our results suggest that the CYP11A1 polymorphism may have a significant influence on the development of advanced and/or high grade prostate cancer and the absence of the CYP11A1 (tttta)4 allele, i.e., the homozygosity for the (tttta)6 or longer allele, could be a useful marker for the prediction of disease progression of prostate cancer. © 2004 Wiley-Liss, Inc.

前立腺がん治療における内分泌療法は進行性前立腺がんの治療の第一選択であるが, 最近, 去勢術やエストロゲンに代わって, それらと同等の臨床効果を有するLH-RHアナログが内分泌治療の大きな位置を占めている. これまでLH-RHアナログとその徐放製剤は, さまざまな臨床の場面における内分泌単独療法あるいは手術や放射線の補助療法として多くの臨床試験でその有用性が確認されてきた. 本稿では, LH-RHアナログ徐放製剤の開発との臨床試験の経緯を中心に概説する.

Recent studies have indicated that the prostate-specific antigen (PSA) gene polymorphisms may be associated with the risk of prostate cancer in Caucasian populations. To verify the association, we examined the PSA polymorphisms at positions -158 and -252 in 300 prostate cancer cases, 216 benign prostatic hyperplasia (BPH) cases, and 266 controls by the PCR-restriction fragment length polymorphism analysis. Regarding the PSA polymorphism at position -158, the A allele was less common in the Japanese population (A 0.22, G 0.78) than that in other ethnic populations (A 0.37-0.52, G 0.48-0.63). No significant associations were found between the polymorphism and the risks of prostate cancer (P=0.530) and BPH (P=0.740) and between the polymorphism and the serum PSA level (P=0.626). As for the polymorphism at position -252, no significant results were also found. In conclusion, the PSA polymorphisms may not be associated with the risk of prostate cancer development and its disease progression and the risk of BPH in Japanese men, and may also be not related to the serum PSA level in Japanese men with prostate cancer.

We elucidated the role of methylation in the promoter region of the 1 gene in bladder carcinogenesis, particularly in those comprising carcinoma in situ.A total of 49 cases of transitional cell carcinoma of the bladder obtained from transurethral resection were examined. Methylation status of the 1 promoter region was analyzed by methylation specific polymerase chain reaction from chemically modified DNA after Na-bisulfite treatment. Loss of heterozygosity on 16q was examined by blunt end single strand DNA conformation polymorphism using 4 tetranucleotide repeat microsatellite markers assigned on 16q13 to 22.1. E-cadherin expression was evaluated by immunostaining on formalin fixed, paraffin embedded tissue sections using anti E-cadherin murine monoclonal antibody, HECD1 and standard avidin-biotin immunoperoxidase complex technique.Analysis of the 49 bladder transitional cell carcinoma samples showed 1 promoter methylation in 23 (47%). Methylation of the 1 gene did not correlate with tumor stage (p = 0.2097) but with high grade transitional cell carcinoma (p = 0.0416). 1 promoter methylation was observed at a significantly higher frequency in the carcinoma in situ positive group than in the carcinoma in situ negative group (16 of 18 cases or 89% versus 7 of 31 or 23%, p0.0001) and it strongly correlated with abnormal E-cadherin expression (p0.0001). We found 16q loss of heterozygosity in 16 of 47 cases (34%), which correlated with higher histological grade (p = 0.0069) but not with the presence of the carcinoma in situ component (p = 0.1235).This study showed that 1 gene promoter methylation is strongly associated with bladder transitional cell carcinoma comprising carcinoma in situ.

A 43-year-old woman with mental retardation, epilepsy, and urinary stone disease had a right renal tumor. Acne-like anthema around the nose and dental pits of the nine teeth were typical signs of tuberous sclerosis (TSC), and the biopsy finding of the facial anthema was consistant with TSC. The pathological diagnosis of laparoscopic nephrectomy was renal cell carcinoma in the hemorrhagic cyst. The TSC-related renal cell carcinoma tends to develop bilaterally in younger individuals compared with the sporadic RCC. This case is the 27th case of TSC-related RCC in Japan.

CCND1 mRNA is alternatively spliced to produce 2 transcripts, and the splicing pattern may be modulated by a frequent A870G single-nucleotide polymorphism within the conserved splice donor site of exon 4. Several studies have suggested a significant association between the CCND1 genotype and onset or progression of various cancers. To investigate the correlation of the polymorphism with genetic susceptibility to PCa and its disease status, we examined the polymorphism in 214 cases of PCa, 234 cases of BPH and 254 male controls. The CCND1A allele was more frequently observed in the PCa group (p = 0.015) and the BPH group (p = 0.018) than the control group. Men with the AA genotype had an increased risk of PCa (aOR = 1.93, 95% CI 1.13–3.30, p = 0.016) and BPH (aOR = 1.84, 95% CI 1.09–3.09, p = 0.023) compared to those with the GG genotype. No significant association was observed when men with the AG genotype were compared to those with the GG genotype (PCa: aOR = 1.00, 95% CI 0.65–1.54, BPH: aOR = 0.91, 95% CI 0.60–1.39). The risk of PCa associated with the AA genotype appeared to be stronger in men aged 73 years or younger (aOR = 2.89, 95% CI 1.38–6.01, p = 0.005), whereas no association was found in men older than 73 years (aOR = 1.02, 95% CI 0.44–2.34). No significant difference in genotype frequency was found among patients with low-, intermediate- and high-grade tumors (p = 0.730) or between patients with localized and metastatic PCa (p = 0.679). However, in patients with high-grade or metastatic PCa, a significantly increased risk associated with the AA genotype compared to controls was observed, while no significant results were found in those with low/intermediate or localized PCa. The A allele of the CCND1A870G polymorphism was recessively associated with susceptibility to PCa and BPH in a Japanese population, giving a 2-fold increased risk of PCa and BPH in men with the AA genotype compared to those with the GG genotype. Although the risk of PCa associated with the AA genotype appeared to contribute especially to men aged 73 years or younger and the A allele may be associated with disease status of PCa, these conjectures require validation in future studies on a larger number of subjects. © 2002 Wiley-Liss, Inc.

The amplification and overexpression of the human epidermal growth factor receptor 2 gene HER-2 (also known as c-erb-B2 or neu) have been shown to be associated with bladder cancer and its progression. Recent studies indicated an association between the Ile to Val polymorphism at codon 655 of HER-2 and susceptibility to breast cancer. To investigate the correlation between the Ile/Val polymorphism and the susceptibility and progression of bladder cancer, we analyzed the polymorphism in 232 patients with transitional cell carcinoma of the bladder and 408 normal controls. The frequencies of the Ile/Ile, Ile/Val and Val/Val genotype were 75.9%, 21.6% and 2.6%, respectively, in patients with bladder cancer and 75.7%, 23.0% and 1.2%, respectively, in controls. Statistical analyses of the genotype prevalence showed no significant difference between bladder cancer patients and normal controls (p = 0.419). Moreover, no significant differences in the genotype prevalence were observed when the patients were stratified according to the tumor grade, stage and smoking habits. When the Ile/Ile genotype was compared to the Ile/Val and Val/Val genotypes, a significant difference was found only between the patients with tumor stage Ta and those with T1-4 (age, gender and smoking habits-adjusted odds ratio = 2.13, 95% confidence interval = 1.09-4.15, p = 0.027). When the Ile/Ile + Ile/Val genotypes compared to the Val/Val genotype, no significant findings were observed. These results suggested that the HER-2 polymorphism at codon 655 is unlikely to be associated with the onset of bladder cancer. Furthermore, the findings suggest no association between this polymorphism and the disease progression in bladder cancer, although the possibility remains that the Ile/Ile genotype may be related to an increased risk of disease progression.

A patient with non-seminomatous germ cell tumor of testis underwent operations for metastases in the lung and mediastinum three times, when the serum AFP level remained remarkably high despite of intensive chemotherapy, and has been disease-free for three years after the last treatment. Our experience illustrates that the salvage surgery even under high serum marker levels may provide a beneficial outcome for selected cases of chemotherapy-resistant germ cell tumors.

Purpose Laparoscopic nephrectomy is being employed in renal transplantation because of its minimal invasiveness, and several modifications in surgical procedures have been proposed. We devised a new technique of retroperitoneoscopic hand-assisted nephrectomy (RHAN) for live donor. We report the early experiences with this technique in 5 cases of live renal graft donor. TECHNIQUES AND SUBJECTS: The donors are placed in a modified decubitus position under general anesthesia, and all the laparoscopic surgical procedures were performed retroperitoneally using 3 port sites and a sealing device (LAP DISC) under a pressure of 10 mmHg. The LAP DISC is placed through a para-rectus abdominal skin incision of approximately 8 cm in length into the retroperitoneal cavity and used as a rout for instrumental as well as hand-assisted manipulations during the surgery. The hand-assistance through the LAP DISC made the surgical manipulation considerably easier and allowed the immediate removal of the graft after the interruption of the renal blood flow. This procedure was applied to 5 subjects, 4 in the left and one in the right kidney. Results The operating data were 264-359 min for operating time, 0.9-3.9 min for warm ischemic time and 40-755 ml for intra-operative blood loss, respectively. The serum creatinine level of the recipients at day 7 was 0.9-2.7 mg/dl. These values, except for operating time, were at the same range as those of the open live donor nephrectomy in our clinic. The 5 donors discharged 7-9 days after RHAN without any surgical complications. Conclusion Our technique of RHAN will be a minimal invasive one in terms of both for the donors and the grafts, and be widely acceptable for donor nephrectomy on either side.

Solid pseudopapillary neoplasm of the pancreas is a rare tumor with unique clinicopathological features. Although it is considered to grow slowly, little is known about its doubling time.We encountered a young Japanese woman with a solid pseudopapillary neoplasm of the pancreas that had been detected at another hospital 5 years previously but was resected at our hospital. The tumor showed only a solid component without any cysts. Computed tomographic scans taken 5 years apart were compared to determine the tumor doubling time.The tumor doubling time according to the formula of Schwartz and co-workers was determined to be 765 days.These findings confirm that this tumor grows quite slowly and also support long disease-free periods even in patients who have recurrence or metastases.

PURPOSE Ischemia/reperfusion injury associated with organ transplantation affects early graft function and acute rejection. Recently, it has been suggested that ischemic insult increases the immunogenicity of the organ. The purpose of this study was to determine the expression of a cell adhesion molecule, CD80, which plays an important role in the costimulatory pathway for full T-cell activation in organ transplantation. MATERIALS AND METHODS Wistar male rats weighing 150-180 g were divided into control group and ischemia groups with temporary clamping of the left renal artery for 30, 60 and 180 minutes. The left kidneys obtained at 1 hour, 1, 3, 7 and 14 days after reperfusion were subjected to total RNA extraction followed by reverse transcriptase-PCR (RT-PCR), fluorescence immunostaining and histological staining. RESULT The expression of CD80 by RT-PCR was not observed in the control group, but was observed in the ischemia groups from 1 to 14 days after reperfusion. Fluorescence immunostaining of CD80 was positive in the ischemia groups, but not in the control group. CD80 expression was detected mainly in the endothelium of the glomeruli and the peritubular vessels. CONCLUSION These results indicate that CD80 is upregulated by ischemic insult, and that the costimulatory pathway may be enhanced by ischemia/reperfusion injury without alloantigens.

We investigated native Japanese subjects whether C702T, C936T and G1612A polymorphisms in the 3' untranslated region (3'-UTR) of vascular endothelial growth factor (VEGF) gene are associated with the risk of renal cell carcinoma (RCC). Genomic DNAs from 145 RCC patients and 145 healthy controls were examined by polymerase chain reaction-based restriction fragment length polymorphism. Variant allele frequencies of C702T, C936T and G1612A were 0.00, 0.20 and 0.13 in the controls, respectively. The C702T and G1612A allele frequencies were significantly different between the Japanese population and the Caucasian population reported elsewhere. For each of C936T and G1612A polymorphisms, there was no statistically significant difference in the distribution of genotype frequencies between the cases and controls. Odds ratios and 95% confidence intervals computed by logistic regression analyses were not statistically significant. Stratification for the RCC cases according to pathological cell subtype, grade or stage failed to reveal any significant heterogeneity with respect to the genotype of each VEGF polymorphism. We revealed that there are significant ethnic differences in the C702T and G1612A allele frequencies, but suggested that C702T, C936T and G1612A polymorphisms in the 3'-UTR of VEGF gene are not associated with the risk of RCC, at least in Japanese population.

A case of renal angiomyolipoma rapidly growing during pregnancy with tumor thrombus into the inferior vena cava is reported. Angiomyolipoma in a 31-year-old woman was incidentally found by ultrasonography. CT scan revealed a fat-containing tumor in the right kidney with 4 cm in diameter. The patient was followed at outpatient clinic without any treatment. Fifteen months later, the post-delivery follow-up CT scan showed that tumor size had grown up to 11 cm in diameter. Although laparoscopic right nephrectomy was tried, open transperitoneal right nephrectomy was performed because the tumor thrombus extending into the inferior vena cava was found during the laparoscopic procedure. Pathological diagnosis was angiomyolipoma of the kidney. There are several reports that indicate angiomyolipoma grows rapidly during pregnancy. Our case demonstrates that careful follow-up is required for angiomyolipoma in women with possible conception and delivery.

エンドトキシン (ET) 除去フィルターの長期使用によるET除去能の変化は不明な点が多い. そこでコンソール用ET除去フィルター2種類を16か月間使用し, ET除去能の変化を比較するとともに, その相違を電子顕微鏡観察から検討した. ダイアライザー直前の透析回路に, いずれも膜素材がポリスルフォン (PS) のニプロCF-609, 東レTET-1.0のいずれかを設置した. 透析液が供給されてから10分後に, フィルター前後のサンプルポートから透析液を採取し, ET濃度をフィルター設置直後, 6, 10, 16か月後に測定した. ET濃度測定は比濁時間分析法を用いた. また使用前と使用16か月後にフィルター膜表面を電子顕微鏡で観察した. 観察期間中, CF-609を通過した透析液中のET濃度はいずれも測定感度以下であり, 使用時間も最長1656時間に及んだ. 一方TET-1.0は3本中2本で, 6か月後にはET濃度が測定限度以上になった. これは使用時間にして600時間程度で発生した. 膜微細構造はTET-1.0に直径1μmの穴が膜全体に存在し, 使用後はCF-609の膜表面に多くの付着物が観察された. またすべてのフィルターにPseudomonas属が検出された. 2種類のフィルターの長期ET除去能は異なったが, 両フィルターとも16か月間装着し, 使用時間が1600時間を越えても, 完全基準を維持したET除去が可能であった. 特にCF-609は16か月, 1600時間以上使用してもET濃度は測定感度以下を維持していた. この差は膜の分画分子量や微細構造の相違による可能性があると思われた.

Metastasis, the most characteristic nature of cancer, has been and still is a long-standing problem in cancer therapy. Irrespective of variety of extensive challenges consisting of clinical and basic researches, any clinically effective measure to control the metastasis has not yet been established. Recent advances in bioscience and biotechnology, however, strongly suggest that there are some promising approaches to antimetastaic treatments. Collaborative studies with clinicians, technologist and basic scientist will play a crucial role in obtaining fruitful results.

Vascular endothelial growth factor (VEGF)-related factors are believed to regulate angiogenesis, an essential event in the growth of solid tumors. In this study, we investigated the expression of VEGF-related factor genes (VEGF, VEGF-B, and VEGF-C) and their receptor genes (VEGFR-1 and VEGFR-2) in renal cell carcinoma (RCC). There were significant differences in the expression level of VEGF, VEGFR-1 and VEGFR-2 between RCC and the corresponding normal renal tissue. The expression level of VEGF in the tumor tissue significantly correlated with those of VEGFR-1 and VEGFR-2. Expression levels VEGF-B and VEGF-C genes were not significantly different between RCC and normal renal tissue. A moderate to high protein expression for VEGF, VEGFR-1, and VEGFR-2 was observed in both the tumor cells and the endothelial cells, whereas the protein expression was low for VEGF-B and VEGF-C. The present results suggested that VEGF and its receptors VEGFR-1 and VEGFR-2 cooperates to play a crucial role in the angiogenesis of RCC, while VEGF-B and VEGFR-C may not. Furthermore, since VEGFR-1 and VEGFR-2 proteins were expressed in the tumor cells as well as in the endothelial cells, these receptors may also be responsible for the progression of RCC.

To assess the clinical significance of nonpalpable localized prostate cancers with relatively favorable six sextant biopsy features in Japanese men.136 nonpalpable prostate cancers of which biopsy features confined to (1) a Gleason score of 6 or less, (2) one or two positive cores per six sextant cores, and (3) 50% or less involvement of any positive core were collected. The Gleason score, tumor extension, and cancer volume were compared with preoperative serum PSA and PSA density for the patients who underwent radical prostatectomy. PSA doubling time was measured for the patients who were treated expectantly.Treatments chosen for 136 patients with favorable biopsy features were radical prostatectomy alone for 48 and with preoperative androgen deprivation for 30, radiation to the prostate for 12, androgen deprivation therapy for 21, and watchful waiting for 25. Of 48 patients who underwent radical prostatectomy without androgen deprivation therapy, 25% had nonorgan-confined cancers. Seven cancers (14.6%) were Gleason score of 7, but no cancers were 8 or greater. Among 42 prostatectomy specimens for which cancer volume was measured, 22 (52.4%) had cancer volume0.5 cm(3). Pretreatment serum PSA levels were correlated neither with the Gleason score, tumor extension nor cancer volume. There was only one nonorgan-confined cancer in the 23 cancers for which PSA density was0.2 ng/ml/g. The ability of PSA density to predict cancer volume0. 5 cm(3) was 0.61 using a cut-off of 0.2 ng/ml/g. Of the 25 patients treated expectantly, the PSA doubling time was less than 2 years for 3 patients, while it was stable or fluctuated for 13.Tumor extension can be predicted based on PSA density in nonpalpable prostate cancer with favorable biopsy features, but predictability of cancer volume based on PSA or PSA density is not satisfactorily high. New parameters or biomarkers that complement needle biopsy findings are needed to predict clinical significance of T1c prostate cancer with favorable biopsy features.

Neovascularization, an essential event for the growth of solid tumors, is regulated by a number of angiogenic factors. One such factor, vascular endothelial growth factor (VEGF), is considered to exert a potent angiogenic activity, as indicated by immunohistochemical and molecular evidence. In this study we investigated the serum VEGF level (s‐VEGF) in patients with renal cell carcinoma (RCC). s‐VEGF in peripheral blood samples was analyzed in 40 RCC patients and 40 patients without cancer (controls) using a sandwich enzyme‐linked immunoassay. In 20 RCC patients, serum samples were obtained separately from the bilateral renal veins. s‐VEGF was also measured before, 4 and 8 weeks after nephrectomy in 11 patients. There were significant differences in s‐VEGF between the RCC patients and the controls (207.3 ± 32.9 vs. 71.5 ± 9.1 pg/ml, mean ± SE) (P < 0.005), between the tumor‐bearing renal veins and the contralateral ones (P < 0.01), between the pre‐ and post‐nephrectomy situations (P < 0.01) and among the various parameters of tumor status such as tumor extent (P < 0.001) and existence of metastasis (P < 0.001). s‐VEGF significantly correlated with the tumor volume obtained by a three‐dimensional measurement (r= 0.802, P < 0.0001). The sensitivity and specificity of s‐VEGF at the cut‐off level of 100 pg/ml, as determined by the receiver‐operating‐characteristics curve, were 80.0% and 72.5%, respectively. The results indicate that tumor tissue of RCC liberates VEGF into the systemic blood flow and that s‐VEGF is a possible marker for RCC.

PURPOSE Up to 40% of surgically treated prostate cancers are bound to be understaged by using current diagnostic modalities. To improve on current staging methods for prostate cancer, we evaluated whether nested reverse transcriptase-polymerase chain reaction (RT-PCR) for prostate-specific antigen (PSA) mRNA can improve preoperative staging of prostate cancer. MATERIALS AND METHODS From May 1996 through November 1997, 30 patients with prostate cancer (T1-T3) were evaluated for PSAmRNA in their peripheral blood by nested RT-PCR before radical retropubic prostatectomy. RESULTS A highly sensitive RT-PCR assay employed detected one PSA-expressing cell (LNCaP) diluted into ten million mononuclear cells. All 15 controls, including 9 women, showed negative PSAmRNA in their peripheral blood, whereas 16 of 30 (53%) patients with prostate cancer showed positive PSAmRNA in their preoperative peripheral blood. Interestingly, 7 patients with positive PSAmRNA had pathologically organ-confined prostate cancer. No significant relationship was demonstrated between positive PSA-PCR results and clinico-pathological parameters such as clinical stage, pretherapeutic serum PSA, pathological stage, seminal vesicle invasion, lymph node metastasis, vascular invasion, or Gleason sum. CONCLUSION Our present study showed that the results of PCR-based PSAmRNA assay had no significant association with clinico-pathological parameters. However, the prognostic significance of detecting the circulating prostate-specific signals requires a longer follow-up, which is currently under study.

It has been considered that the urethral obstruction influence the function and the nerve innervation of the bladder. In this study, the changes in the bladder function and the nerve growth factor (NGF) synthesized in the bladder were systematically analyzed both during partial urethral obstruction and after its relief in the rat. The maximum contraction pressure was temporally decreased and then increased 1.5 times of the normal level 6 week after the obstruction. NGF in the bladder, measured by ELISA method, was rapidly increased 5 times of the normal level 1 day after the obstruction. It gradually decreased 2 weeks after the obstruction but did not recover to the normal level. The maximum contraction pressure and the bladder NGF recovered to the normal level after the removal of 1 to 6 weeks obstruction. These results suggest that partial urethral obstruction reversibly increases the contractility and the NGF synthesis of the bladder.

We investigated expression of the vascular endothelial growth factor (VEGF) gene and its receptor gene (flt-1) in 30 patients with transitional cell carcinoma (TCC) of the urinary bladder by Northern blot hybridization analysis. The VEGF transcript was observed in all of the tumors and the normal mucosae. Of the 20 tumors in which a comparative study was done, eight (40.0%) overexpressed the gene with a tumor versus normal ratio of equal to and greater than 3.0. Invasive TCCs expressed significantly more VEGF gene than superficial TCCs. Cytoplasm of tumor cells was positively stained by immunohistochemistry with an anti-VEGF monoclonal antibody, while the intratumoral endothelial cells and the vascular smooth muscle cells were weakly positive for the staining. TCCs, normal mucosae and human umbilical endothelial cells expressed flt-1 gene, while leucocytes from peripheral blood did not. The expression level of flt-1 gene significantly correlated with that of the VEGF gene in the tumor. These results indicate that the VEGF gene is frequently overexpressed in TCC of the urinary bladder, especially in muscle invasive tumors, and that a paracrine system including VEGF and flt-1 exists between the TCC cells and the adjacent endothelial cells so as to regulate the angiogenesis in this tumor.

We previously reported that detection of telomerase activity in urinary exfoliated cells obtained from urothelial cancer patients by telomeric repeat amplification protocol (TRAP) assay is a more sensitive method of diagnosis than conventional urine cytologic examination, particularly in patients with grade 1 tumors. To establish this method as a noninvasive screening test for the diagnosis of urothelial cancers, we performed the semi-quantitative analysis of telomerase activity using Telomerase PCR ELISA™. Spontaneous voided urine samples were obtained from 65 urothelial and 58 non-urothelial cancer patients. When the mean + 2 standard deviation of telomerase activity in urine sediments of non-urothelial cancer patients was arbitrarily determined as a cut-off, the sensitivity of TRAP enzyme-linked immunosorbent assay (ELISA) and the conventional cytology were 57% and 35%, respectively. Detection rate was significantly higher in semi-quantitative TRAP assay than in conventional cytologic examination in grade 1 cancer patients (52% vs. 5%, p = 0.00195). False positives were detected in 5% of non-urothelial cancer patients without pyuria and in 11% of non-urothelial cancer patients with pyuria (p = 0.395). Telomerase activity was enhanced in some cases after phenol extraction or extracting epithelial cells by using Dynabeads of macroscopic hematuria and pyuria, indicating that hematuria and pyuria might contribute to false negatives. In conclusion, the TRAP-ELISA method is superior to the standard TRAP assay in quantitativeness and simplicity of the experimental procedure. Detection of telomerase activity in urine sediments is particularly useful for the diagnosis of low-grade tumors. However, telomerase activity in patients with high grade tumors often might be underestimated due to the excessive amount of exfoliated epithelia with necrotic tissues, hematuria, and pyuria.

A rare case of anal bleeding caused by rectal stone after uretero-ileoceco-proctostomy is reported. A 66-year-old man was admitted to our hospital complaining of anal bleeding. He had a history of cystoprostatectomy with uretero-ileoceco-proctostomy for prostatic adenocarcinoma 25 months prior to the present admission. Mucosal bleeding from the point of stone formation around the staples at the uretero-ileoceco-rectal anastomosis was found by sigmoidoscopy and the bleeding was treated endoscopically by thrombin spraying and clipping. Furthermore, the stones and staples at the uretero-ileoceco-rectal anastomosis were endoscopically removed with forceps. To our knowledge, severe mucosal bleeding from the point of stone formation around the staples at the site of intestinal anastomosis has not previously been reported.

To evaluate the feasibility of intraarterial infusion of microencapsulated anticancer drugs (chemoembolization), collective data on 1013 cancer patients were reviewed. Ethylcellulose microcapsules containing mitomycin C (median total dose 20 mg), cisplatin (60 mg) or peplomycin (40 mg) were given to tumor-feeding arteries by bolus infusion in 79% of the patients and by fractionated infusion in the others, as a palliative (71%) or preoperative measure (29%). The target sites were the liver (42%), kidney (24%), intrapelvic organs (18%), lung (4%), head and neck (3%), bone (1%) and others (9%), excluding the central nervous system and gastrointestinal tract. The incidence of overall adverse effects ranged from 0.2 to 54.9%, but grade 2-3 hematological, renal and hepatic toxicities, local pain, abdominal discomfort, cutaneous reaction, remote embolization and infection were10%. Nine patients (0.9%) in the early stages of trials suffered serious complications including treatment-related death in two with critical underlying diseases of the target organs. The remaining patients recovered from the adverse effects, except for grade 2 cutaneous reactions, within 2 months by routine palliative measures. Aor = 50% tumor reduction was seen in 28% of 427 evaluable tumors (42% for25-cm2 tumors and 20% foror = 25-cm2 tumors) with a median treatment number of one. The response rate depended on both the tumor size and the treatment number (P0.05), but it was not affected by prior therapies. Mitomycin C microcapsules produced a higher response rate. Complete or partial remission of intractable pain and genitourinary gross hemorrhage was found in two-thirds of eligible patients. The results indicate that this treatment modality, though restricted by catheter technique, can be applied to various tumor lesions with an acceptable morbidity and prospective trials are justified to evaluate the potential role of such a targeted chemotherapy.

BACKGROUND: The objective of this study is to evaluate the relationship between PSA value and prognosis of the patients with stage D2 prostate carcinoma. METHODS: Serum prostate specific antigen was analyzed in 61 patients with stage D2 prostate carcinoma submitted to hormone therapy. RESULTS: The median values of PSA parameters were 77.6 ng/ml for the initial PSA, 91.8% for the maximal decrease, 2.7 ng/ml for the nadir, 1.1 months for the half-time time, 3.0 months for the time to nadir, 3.2 months for the doubling time after progression and 0.39 for the ratio of antemortem versus initial PSA. The median biochemical progression-free time was 15.0 months and the median actuarial survival after progression was 24.9 months. The progression-free time was significantly correlated with the normalization of PSA (p < 0.001) and the initial PSA of less than 100 ng/ml (p < 0.05), and the survival time after progression was significantly correlated with the doubling time (p < 0.05). The normalization of PSA was affected by initial value, maximal decrease rate and half-life time of PSA respectively, but not by the histological grade of the primary tumors. The doubling time was not correlated with these factors nor with the progression-free time. CONCLUSION: The results show that the initial value, nadir level and doubling time of PSA can be used as prognostic parameters for prostatic carcinoma. Both the low ratio of premortem versus initial PSA, which may reflect an increase of stem cell fraction, and the PSA doubling time after relapse, which seems similar to or shorter than that of untreated cases, will indicate an aggressive potential of hormone-refractory tumors.

A novel technique of urinary diversion was designed by interposition of an intussuscepted ileal segment between the ureters and the rectosigmoidal pouch, thus preventing ureteral reflux as well as stenosis at the uretero-enteric anastomosis, possible occurrence of urocolonic carcinoma, and frequent evacuation or incontinence. Since all the procedures were limited to the lower abdominal cavity, the surgical invasiveness was compatible with that of an ileal conduit. Our early experience in 15 patients showed that this technique can be considered for those in whom the urethra is not available.

Objective Locally advanced prostate carcinoma frequently causes lower urinary tract symptoms and is a clinical challenge when radiation and/or hormone therapy fail. We investigated whether cystoprostatectomy with urinary diversion benefits patients with locally advanced prostate carcinoma in terms of quality of life and prognostic outcome. Patients and methods Between 1989 and 2001, we performed 15 cystoprostatectomies for stage C-D1 prostate carcinoma with bladder neck involvement. Of these patients, 5 underwent ileal conduit, 8 rectal bladder, 1 Koch pouch, and 1 ureterocutaneostomy. All the patients received neoadjuvant and/or adjuvant hormonal therapy. In the same period, 28 patients underwent retropubic prostatectomies and 15 patients received hormone therapy alone for stage C-Dl disease. These patients were included as references. Results Lower urinary tract symptoms caused by bladder involvement were controlled well until the end of follow-up for all the patients in the cystoprostatectomy group. There was no statistically significant difference in QOL score assessed with the EORTC QLQ-C30 questionnaire between the prostatectomy group and the cystoprostatectomy group, while that in the hormone therapy group was lower than those in the surgery groups. There was no statistically significant difference in 5-year PSA-relapse-free survival among cystoprostatectomy, prostatectomy, and hormone therapy groups. Patients in the hormone therapy group died earlier than those in the prostatectomy group (p = 0.02), while those in the cystoprostatectomy group did not. Conclusion These results suggest that total cystoprostatectomy with urinary diversion is a valid option, in terms of disease control and QOL, for prostate cancer patients whose tumor is infiltrating into the bladder.