Segawa N

Prognostic significance of neuroendocrine differentiation, proliferation activity and androgen receptor expression in prostate cancer

Androgen, acting via the androgen receptor (AR), is associated with the development and progression of prostate cancer. Anti‐androgen therapy is widely used to manage prostate cancer. However, the conversion of the tumor from a hormone‐sensitive to a hormone‐insensitive status causes such therapy to fail. Several mechanisms have now been put forward for this conversion, including neuroendocrine (NE) differentiation of the tumor cells. In this study, we evaluated the prognostic significance of tumor‐cell proliferation activity, NE differentiation and AR expression. Formalin‐fixed, paraffin‐embedded sections were prepared from 42 patients with adenocarcinoma of the prostate. Using antibodies to AR, the Ki‐67 antigen (MIB‐1), chromogranin A and synaptophysin, immunohistochemical expression of AR, tumor proliferation activity and NE differentiation were analyzed. Our study revealed that AR expression was significantly lower in adenocarcinoma (52.2 ± 27.1%) than in non‐tumorous prostate tissue (68.3 ± 18.3%; P < 0.001). NE differentiation was found in 50% of the tumors, which was correlated with the Gleason score (P < 0.05). An univariate analysis revealed a significant correlation between progression‐free survival with both AR expression (P < 0.01) and proliferation activity (P < 0.001). NE differentiation was not a prognostic factor in this study.

Expandable metallic stent placement for nutcracker phenomenon

A 40-year-old woman presented with asymptomatic gross hematuria caused by the nutcracker phenomenon. Despite treatment with hemostatic agents and injection of silver nitrate into the renal pelvis, the hematuria had continued, and severe anemia (hematocrit 17%) had developed. We performed expandable metallic stent (EMS) placement across the left renal vein. Although mild hematuria continued, the anemia resolved after this interventional radiotherapy. EMS placement is a minimally invasive therapy for the nutcracker phenomenon.

Expression and somatic mutation on androgen receptor gene in prostate cancer.

Background: Lack of androgen receptor (AR) expression or mutation on the AR gene creates the tendency for androgen independence and progression of prostate cancer. However, the association between the progression and AR expression or mutations is still controversial. In this study, we evaluated the prognostic significance of AR expression and mutations in prostate cancers.

Basal cell carcinoma of the prostate: Report of a case and review of the published reports

Abstract:  Prostatic basal cell carcinoma (BCC), a distinctive variant of adenocarcinoma, is rare. We report a patient with pure basaloid BCC showing an extraprostatic extension and lymph node metastases. A 67‐year‐old man with urinary outlet obstruction was referred to our hospital. Digital rectal examination disclosed a stony hard prostate. Serum prostate‐specific antigen and prostatic acid phosphatase were within the normal range. Transrectal needle biopsy of the prostate was followed by transurethral resection as symptomatic treatment. The lesion was diagnosed histopathologically as BCC. Despite antiandrogen therapy distant metastases developed, and the patient died 5 months postoperatively. We discuss the histological and immunohistochemical findings in this case.

Total Cystectomy Versus Bladder Preservation Therapy for Locally Invasive Bladder Cancer: Effect of Combined Therapy Using Balloon-occluded Arterial Infusion of Anticancer Agent and Hemodialysis With Concurrent Radiation

Objectives:We tested the usefulness of balloon-occluded arterial infusion (BOAI) of anticancer agent (cisplatin/gemcitabine), concomitant with hemodialysis, which delivers an extremely high concentration of anticancer agent to the site of a tumor without systemic adverse effects, along with concurrent radiation [Osaka-Medical College (OMC)-regimen] in patients with locally advanced bladder cancer. The results were compared with those of cystectomy. Methods:One hundred twenty-four patients were assigned to receive cystectomy (Gp1, n = 62) or OMC-regimen (Gp2, n = 62). In Gp2, patients besides undergoing complete response subsequently received secondary-BOAI with gemcitabine (1600 mg). Results:In Gp1, 27 of 62 patients (43.5%) suffered disease recurrence, and more than half died within 1 year; the remainder died thereafter. The overall 5-, 10-, and 15-year survival rates were 53.8%, 46.0%, and 40.0%, respectively. In contrast, in Gp2, >70% of patients (44 of 62), especially >95% of patients with locally invasive tumors achieved complete response with no evidence of recurrent disease or metastasis after a mean follow-up of 163 (range, 32–736) weeks. At 14 years, overall survival was significantly improved at 79.7% (P = 0.015 vs. Gp1). Moreover, salvage therapy for secondary-BOAI with gemcitabine was effective in all 3 patients with T4 tumors or lymph node involvement, who showed stable disease (SD) after primary therapy with CDDP. No patients suffered Grade III or more severe toxicities. Conclusion:OMC-regimen, a new strategy for patients with locally-invasive bladder cancer, can be curative not only in patients for whom cystectomy is indicated, but also in patients whose condition is not amenable to curative treatment and for whom merely palliative treatment would otherwise seem the only option.

Marked regression of liver metastasis by combined therapy of ultrasound-mediated NFkB-decoy transfer and transportal injection of paclitaxel, in mouse

Nuclear factor‐kappaB (NFkB) plays a pivotal role in cancer progression. In this study, we developed a decoy cis‐element oligo‐deoxyribonucleic acid against NFkB‐binding site (NFkB‐decoy), which effectively inhibits NFkB activity, and tested the effect of combined therapy comprising local transfection of NFkB‐decoy into the liver and transportal injection of paclitaxel on cancer growth and metastasis using an orthotopic murine model of colon cancer liver metastasis. For NFkB‐decoy transfection, we employed a novel approach using ultrasound exposure with an echocardiographic contrast agent, Optison. We examined the influence of NFkB‐decoy transfer on susceptibility to paclitaxel in cancer cells and the mechanism involved using several in vitro analysis systems. We then studied the in vivo effect of combined NFkB‐decoy transfer and paclitaxel in preventing cancer progression using a murine model of liver metastasis created by splenic injection of a human colon cancer cell line, HT29. In vitro experiments, including MTT‐assay, fluorescence‐activated cell sorter and cDNA array analysis, revealed that NFkB‐decoy transfer significantly increased the susceptibility of cancer cells to paclitaxel, and that decreased expression of anti‐apoptotic genes along with increased expression of genes relevant to the apoptosis‐promotor may be involved. In vivo experiments showed that local transfection of NFkB‐decoy into the liver followed by portal injection of paclitaxel effectively induced cancer cell apoptosis in the liver metastasis, and significantly prolonged animal survival compared to controls, without notable side effects. In conclusion, a combination of local NFkB‐decoy transfer into the liver and transportal injection of paclitaxel may be a safe and effective new therapy for liver metastasis.

Effect of combined therapy using balloon-occluded arterial infusion of cisplatin and hemodialysis with concurrent radiation for locally invasive bladder cancer.

Objective:We tested the usefulness of combined therapy using balloon-occluded arterial infusion (BOAI) of cisplatin and hemodialysis, which delivers an extremely high concentration of cisplatin to the site of a tumor without systemic adverse effects, with concurrent radiation in patients with locally advanced bladder cancer. Methods:Patients underwent transurethral resection of the bladder tumor followed by BOAI of cisplatin (100, 200, or 300 mg) concurrent with hemodialysis, via both common iliac veins, for 2 hours after initiation of BOAI. A total of 60.4 Gy of radiation was delivered, starting from the day of BOAI. Results:Forty-one patients (30 males and 11 females, aged 55–98 years) were enrolled and assessable for toxicity and response. None of the patients suffered grade II or more severe toxicities; some experienced grade I blood/bone marrow toxicity, gastrointestinal toxicity, or neuropathy. All patients with histologically confirmed transitional cell carcinoma stage T2 or T3 (29 patients) achieved a complete response and were able to retain their bladder with no evidence of recurrent disease or distant metastasis at a mean follow-up of 132 weeks (range 8–648 weeks) after therapy. Patients with stage T4 tumors, besides transitional cell carcinoma, or lymph node involvement had stable or progressive disease. Conclusion:This therapy is a new strategy for patients with locally advanced bladder cancer. It can be a curative treatment not only in patients for whom total cystectomy is indicated, but also in patients whose condition is not amenable to curative treatment and for whom merely palliative treatment would otherwise seem the only option.

Surgical correction of buried penis after traffic accident – a case report

BackgroundBuried penis, most commonly seen in children, is particularly debilitating in adults, resulting in inability to void while standing and it also affects vaginal penetration. We report a case of buried penis due to a traffic accident, which caused dislocation of the fractured pubic bone that shifted inside and pulled the penis by its suspensory ligament.Case presentationA 55-year-old man was admitted to our hospital with a chief complaint of hidden penis while in the sitting position. He had suffered a pelvic fracture in a traffic accident four years previously, and his penis was covered with suprapubic fat when he was in a sitting position. He was unable to have sexual intercourse. We performed a penile lengthening procedure, including inverse V-Y-plasty of the dorsal skin of the penile root, suspensory desmotomy and fat removal, under general anesthesia. There was a good cosmetic result with satisfactory penile erection, which allowed successful sexual intercourse after surgery.ConculsionWe performed penile elongation surgery with inverse V-Y-plasty of the dorsal skin of the penile root, suspensory desmotomy, and fat removal. Surgical treatment of buried penis achieves marked aesthetic and functional improvement, and benefits the majority of patients, resulting in satisfactory erection and successful sexual intercourse.

Telomerase activity in renal cell carcinoma by modified telomeric repeat amplification protocol assay.

Background: Previous assessments by the conventional telomeric repeat amplification protocol have not been reliable for the quantitation of telomerase activity. We, therefore, determined telomerase activity in renal cell carcinoma (RCC) tissue by the modified sensitive telomeric repeat amplification protocol assay.

Anticancer effect of combination therapy of VP16 and fosfesterol in hormone-refractory prostate cancer.

Objectives:We conducted the present study to evaluate the safety profile and therapeutic value of a combination of etoposide and fosfestrol for treatment of hormone-refractory prostate cancer (HRPC). Methods:Forty patients with HRPC were included in the study. The median age was 71 years (range, 50–86 years), the Gleasons score ranged from 5 to 10, and the median prostate-specific antigen level was 62.6 ng/mL (range, 4.738–30789 ng/mL). The patients received oral etoposide 25 mg/d and fosfestrol 300 mg/d. Results:The response rate in terms of measurable disease, serum prostate-specific antigen level, and overall evaluation was 36.8% (CR: 18.4%; PR: 18.4%), 80% (CR: 55%; PR: 25%), and 40% (CR: 20%; PR: 20%) with a median duration of response of 13.6, 13.5, and 13.5 months, respectively. An objective clinical response for overall evaluation was shown by 90% (CR: 20%; PR: 20%; SD: 50%) of the patients, with a median response duration of 15.7 months; 16 patients (40%) are currently alive without recurrence after a median follow-up period of 21.2 months. The overall survival and progression-free survival was 30.5% and 28.8% at 40 months, respectively. No grade III toxicities occurred in any of the patients. Serial measurements in 34 patients using the Functional Assessment of Cancer Therapy-Prostate showed a significant improvement in quality of life as a result of the therapy. Conclusions:The combination of oral etoposide and fosfestrol is active in patients with HRPC. The regimen is tolerable and has a significant impact on quality of life as measured by the Functional Assessment of Cancer Therapy-Prostate in a limited sample of patients.