Proteomics-based signature for human benign prostate hyperplasia and prostate adenocarcinoma.

Prostate adenocarcinoma often presents at a late stage, due to a lack of early clinical symptoms and lack of accurate objective markers. This study aimed to identify and validate proteomics-based biomarkers useful for prostate cancer diagnosis and to establish a marker-panel for prostate cancer and benign prostate hyperplasia (BPH). Global protein expression patterns in fresh tissue specimens from 8 patients with prostate carcinoma and 16 with BPH were analyzed by two-dimensional gel electrophoresis. Differentially expressed proteins were identified by MALDI-TOF mass spectrometry. We compared our results with those of published studies and defined a set of common biomarkers. We identified 22 differentially expressed proteins between BPH and prostate carcinomas. The up-regulated proteins in cancer compared to BPH included protein disulfide-isomerase, 14-3-3-protein, Enoyl CoA-hydrase, prohibitin and B-tubulin ß-2. Keratin-II, desmin, HSP71, ATP-synthase-ß-chain and creatine kinase-ß-chain were down-regulated. Survey of the literature showed that 15 of our 22 identified proteins have been previously reported to differ in their expression levels between BPH and prostate cancer by other laboratories. The expression patterns of these biomarkers could successfully cluster BPH and adenocarcinomas as well as prostate cancer of low and high Gleason scores. This study validates protein-biomarkers that can be useful for accurate diagnosis and prognostic monitoring of prostate adenocarcinoma. Despite varied prevalence of the disease between different ethnic populations (i.e., high in Sweden, low in Saudi Arabia); the biomarkers indicate that BPH and prostate cancers are biologically 'homogeneous' in their protein expression patterns across wide geographical regions.

Arabic validation of the short form of Urogenital Distress Inventory (UDI-6) questionnaire.

AIMS: To translate and validate the Arabic version of the short form of Urogenital Distress Inventory (UDI-6) questionnaire in a sample of women with lower urinary tract symptoms (LUTS). METHODS: Two native Saudis independently translated the original UDI-6 into Arabic. These two translations were harmonized, and then checked by independent back translation by two English teachers. They collaborated with the clinical investigators to reach a consensus version of the questionnaire. The harmonized version was pre-tested in a pilot study on 20 patients. The final version of the UDI-6 was applied to 68 consecutive patients aged 22 years or over complaining of LUTS for at least 3 months at our tertiary care hospital. The patients were rerated after 1 week to assess test-retest reliability. To assess the capacity of the questionnaire to discriminate between women with and without LUTS, cases, and controls of healthy women sample were involved and assessed. The psychometric properties of the questionnaire, such as reliability and validity were assessed. RESULTS: The correlation co-efficient between ratings was >0.75 and the discriminate power between cases and control were confirmed. The UDI showed good internal consistency total score cronbach alpha = 0.71. CONCLUSIONS: The Arabic version of UDI-6 is a valid and robust instrument and a reliable method to use in daily practice and clinical research.

Changing trends in presentation, diagnosis and management of renal angiomyolipoma: comparison of sporadic and tuberous sclerosis complex-associated forms.

OBJECTIVES: To evaluate the changing management of sporadic renal angiomyolipoma and renal angiomyolipoma associated with the tuberous sclerosis complex (TSC) during the past 16 years. METHODS: We retrospectively reviewed the charts of 60 patients with angiomyolipoma seen at our institutions. RESULTS: The median age at presentation was 45 years (range 7-78). The presentation was pain in 30 patients and hematuria in 13; it was incidentally discovered in 17 patients. Of the 60 patients, 43 were females. TSC was present in 14 patients. The median tumor size was 4 cm (range 0.3-40, mean 6.5 +/- 1.1). Of the 60 patients, 31 were followed up expectantly. Surgery or intervention was needed for 29 patients to control hemorrhage or relieve pain or because of the suspicion of malignancy. Of these 29 patients, 12 underwent nephrectomy, 11 partial nephrectomy, and 6 embolization. The patients treated for hemorrhage had a median tumor diameter of 11 cm (range 2-21). Patients were followed up for a mean of 39.3 +/- 5.4 months. The lesions grew an average of 4.7 +/- 3.4 cm for TSC tumors and 0.6 +/- 0.2 cm for sporadic angiomyolipoma tumors. None of the patients developed renal impairment. Patients with TSC presented at a younger age, had larger and bilateral lesions, and were more symptomatic during follow-up. In the past 6 years, a significant trend was seen toward finding tumors in asymptomatic patients and toward the use of conservative or interventional (embolization) treatment. CONCLUSIONS: Renal angiomyolipoma has a slow growth rate. The preservation of renal function was noted in all our patients. A recent shift was noted toward finding smaller tumors in asymptomatic patients and the use of conservative and interventional treatment.

Pheochromocytoma in children and adolescents: a clinical spectrum.

PURPOSE: The purpose of the study was to identify the spectrum of disease characteristics of pheochromocytoma in children. METHODS: Records of 21 consecutive children diagnosed with pheochromocytoma were reviewed. Patients' age, sex, presentation, associated conditions, diagnostic and imaging modalities used, preoperative preparation, operative details, outcome, and follow-up were recorded. RESULTS: The study included 21 children. Patients were diagnosed clinically and confirmed by biochemical tests. Tumors were localized by imaging studies and all were confirmed pathologically. Patients included 17 with adrenal and 4 with extra-adrenal tumors including 1 in the urinary bladder. Seventeen had sporadic and 4 had familial pheochromocytoma. Associated manifestations were the predominant features in 1 of the 4 patients with familial pheochromocytoma. The patient with bladder pheochromocytoma presented with gross hematuria. Hypertension and visual disturbances were prominent findings in the other patients with sporadic form. Two patients (1 sporadic and 1 familial) had malignant pheochromocytoma. One patient with benign pheochromocytoma had multiple recurrences in chromaffin-containing sites. All patients were treated surgically. Seventeen patients were treated preoperatively with alpha-adrenergic blockade. Two patients continued to have significant visual disturbances. One patient with malignant pheochromocytoma died of the disease, and 1 with recurrent pheochromocytoma had neurologic consequences. CONCLUSIONS: Pheochromocytoma in children has unique characteristics. To our knowledge, this series is one of the largest reports of adrenal pheochromocytoma in children. It also reflects the spectrum of pheochromocytoma in this age group.

Familial pheochromocytoma.

OBJECTIVES: To identify disease characteristics, operative outcome, and prognosis in patients with familial pheochromocytoma. METHODS: Records of 29 patients with familial pheochromocytoma were retrospectively analyzed. Patients' age, gender, presenting symptoms and clinical signs, chemical and radiologic findings, and associated conditions were recorded. RESULTS: Of the 29 patients, 25 were adults and 4 were children. Age ranged from 18 to 52 years (mean age 30.8 years). Twenty patients were females. Of the 29 patients, 26 had adrenal tumors, 2 had extra-adrenal tumors, and 1 had a combined adrenal and extra-adrenal tumor. The patients included 17 with multiple endocrine neoplasia (MEN), 8 with von Hippel Lindeau disease (vHLD), and 4 with Von Recklinghausen disease (vRD). Two patients had malignant pheochromocytoma. All except one patient with MEN had thyroid carcinoma. The two patients with malignant pheochromocytoma had MEN II. All patients were managed by either open or laparoscopic adrenalectomy or excision of extra-adrenal tumors. There was no perioperative mortality. CONCLUSIONS: Associated conditions in patients with familial varieties are often the dominant or initial presentation. Presence of other manifestations of familial pheochromocytoma significantly influenced the clinical course and prognosis. However, it had no bearing on operative outcome of these patients.

The clinical spectrum of phaeochromocytoma: analysis of 115 patients.

OBJECTIVE: To analyse the presentation, manifestations and outcome in consecutive patients with phaeochromocytoma, as this disease has a wide range of pathological and clinical expressions. PATIENTS AND METHODS: The records of 115 patients with phaeochromocytoma were analysed retrospectively, recording the patients' age, sex, presenting symptoms and clinical signs, chemical, radiological and pathological findings and associated conditions. RESULTS: Of the 115 patients, 90 had adrenal tumours, 18 extra-adrenal and seven combined adrenal and extra-adrenal tumours. Ten patients had malignant and 105 had benign phaeochromocytoma. Eighty-six patients had sporadic and 29 had familial phaeochromocytoma, comprising eight with von Hippel-Lindau (VHL) disease, 17 with multiple endocrine neoplasia type II (MEN II) and four with von Recklinghausen disease. Two patients with sporadic phaeochromocytoma had Grave's disease. Ten patients (8.7%) had malignant phaeochromocytoma, of whom two had MEN II. A pregnant woman required prolonged intensive-care management before adrenalectomy and lost a fetus. CONCLUSION: Phaeochromocytoma is an interesting clinical entity with a wide spectrum of pathological and clinical manifestations. The diagnosis of phaeochromocytoma is confirmed by chemical methods, and located using imaging techniques, with computed tomography, magnetic resonance imaging and (131)I-meta-iodobenzyl guanidine radioisotope scanning being the most common. This series reflects the pathological and clinical spectrum of phaeochromocytoma. The presence of other manifestations of familial phaeochromocytoma influenced the presentation and prognosis of these patients.

Crural tunica albuginea autograft for corporoplasty: an experimental animal study of hemodynamic, histopathological, and molecular effects in the long term.

INTRODUCTION: Correction of penile deformity caused by Peyronie's disease by a variety of grafts varies in success. A long-term follow-up shows a significant number of graft scarring and erectile dysfunction. The clinical success of autologous crural tunica albuginea graft (TAG) has not resulted in wide application. AIM: To identify in healthy baboons the limitations and merits of autologous crural TAG over 1 year in a way difficult to pursue in humans. METHODS: Under general anesthesia, eight sexually active adult baboons underwent pharmacological cavernosometry (CM) and cavernosography. TAG from crus was implanted in the distal penile shaft. After 6 months, six animals were reevaluated and two were sacrificed, and the penises were excised. After 1 year, the remaining six animals were evaluated and sacrificed. The TAG and underlying corpus cavernosum (CC) were examined histologically and by Western blot analysis for nitric oxide synthase (NOS), neuronal (nNOS), endothelial (eNOS) and inducible (iNOS) isoforms, and transforming growth factor-beta1 (TGF-beta1). MAIN OUTCOME MEASURES: Sexual activity, CM, cavernosography, histopathology, and Western blot analysis. RESULTS: All animals resumed normal sexual activity 1 month postsurgery. Cavernous pressure was comparable before, at 6 months, and 1 year after surgery. A cavernovenous insufficiency developed in four animals at 6 months, and ceased in two at 1 year. Penile angulation (<20 degrees) was seen in three animals at 6 months, and an additional two at 1 year. Histologically, TAG was indistinguishable from the adjacent tunica with no fibrosis. In CC, iNOS and nNOS decreased at 1 year, whereas there was no change in TGF-beta1 levels. In TAG, there was no significant change in TGF-beta1 and eNOS levels, but there was a significant decrease in iNOS at 1 year. CONCLUSION: Autologous free TAG is associated with normal sexual activity, minimal hemodynamic changes, excellent histological outcome, and no rise in iNOS or TGF-beta1. However, cavernovenous insufficiency, mild penile angulation, and decreased nNOS persisted at 1 year.

Outcome of penile cancer in circumcised men.

PURPOSE: We previously reported on a group of patients with post-circumcision carcinoma of the penis. We now study the long-term outcome of these patients. MATERIALS AND METHODS: We retrospectively reviewed the available charts of 22 patients presenting between October 1979 and May 2000. RESULTS: Of 22 patients 18 underwent ritual circumcision with extensive scar development. Median age at diagnosis was 62.4 years. The penile lesion was dorsal and proximally located in 15 patients. Median delay before diagnosis was 12 months. Clinically 14 patients had stage T1-T2 disease, with 13 having no lymph node involvement and none with distant metastasis, 8 patients had stage T3-T4 disease. A total of 15 patients were treated surgically with total penectomy (10) or conservative local excision (5), inguinal lymph node dissection (9) and subsequent penile reconstruction (3). Pathological staging in 15 patients revealed 10 patients with stage T1 and in 8 patients with lymph node dissection none had nodal metastasis. Histopathological classification was 20 squamous cell carcinoma, 1 sarcoma and 1 verrucous carcinoma. Six patients refused surgery and 1 was referred for palliation. Median followup was 14.5 months and median survival was 14.5 months. The 3-year survival was 42% for stage T1-T2 and 13% for T3-T4 (p = 0.0052). Median survival for the surgical group was 34 months whereas for nonsurgical group was 3 months (p = 0.0016). Recurrence-free survival in the surgical group was 50%. CONCLUSIONS: Penile carcinoma in circumcised men is a distinct disease commonly following nonclassic vigorous circumcision. Delayed diagnosis and deferring surgical treatment are associated with increased mortality.

Genitourinary manifestations of Klippel-Trenaunay syndrome: report of two cases managed with systemic alpha-interferon.

We present our experience of two cases with genitourinary manifestations of Klippel-Trenaunay syndrome. A MEDLINE search for the period 2001-2004 was done using the keywords "Klippel-Trenaunay syndrome", "vascular malformation" and "genitourinary". Only three cases with genitourinary manifestations of this syndrome were reported during this period. Genitourinary problems are rare in Klippel-Trenaunay syndrome; however, their management may be a challenge for the urologist. In one of our patients who failed to respond to endoscopic laser coagulation and partial cystectomy we used systemic alpha-interferon, with a good short-term response.

Laparoscopic ablation of giant renal cyst.

We report a case of a symptomatic giant (18 x 10 x 8-cm) renal cyst in a 40-year-old woman that was marsupialized laparoscopically and excised. The surgical technique, based on progressive decompression of the cyst, is fully described. Excellent results were achieved. The recent application of laparoscopic ablation of different types of renal cysts is reviewed. This minimally invasive technique, when properly mastered, is highly effective and offers results similar to those of open surgery. It is associated with definitive postoperative advantages and is the treatment of choice for very large renal cysts, especially those located anteriorly, when sclerotherapy is ineffective or is contraindicated.

Phase II trial of cisplatin, 5-fluorouracil, and interferon-alpha-2B as first line treatment of advanced urothelial cancer.

Cisplatin based combination chemotherapy remains the mainstay for treatment of advanced urothelial cancer. The combination of 5-fluorouracil and interferon has been found to be effective second line treatment of advanced urothelial cancer. Hence, we tested the combination of cisplatin, 5-fluorouracil and interferon as first line therapy in advanced urothelial cancer. Eligible patients had to have no prior chemotherapy or interferon. Treatment consisted of cisplatin 80 mg/m(2) on day one, followed by 5-fluorouracil 750 mg/m(2) as a daily infusion for 5 days and interferon alpha 2 B 5 MU/m(2) subcutaneously daily on day 1-5 of 5-fluorouracil infusion. Cycles repeated every 21 days. Eighteen patients, of which sixteen were males were enrolled. Median age was 60 years. All patients had transitional-cell carcinoma. The median number of cycles given was 4. Thirteen patients were evaluable for response. Two patients achieved CR and 3 PR for an overall response rate of 28% (95% confidence interval 7% to 49%). Median response duration was 8.3 months. Median survival was 5.5 months. Four patients died secondary to chemotherapy toxicities. Those were GI perforation in one, bronchopneumonia in one, acute renal failure in one and one patient died at home 3 weeks following the third cycle. The above regimen demonstrates excessive toxicity and moderate activity. It cannot be recommended in its present format. Novel anti-cancer agents need to explored.

Multi-institutional long-term experience with conservative surgery for invasive penile carcinoma.

PURPOSE: Invasive squamous cell carcinoma of the penis occurs on the glans, prepuce, glans and prepuce, coronal sulcus and shaft. Penile squamous cell carcinoma subsequently invades local structures, corpora cavernosa and the urethra, and metastasizes to the inguinal lymph nodes. Invasive squamous cell carcinoma of the penis usually requires total or partial penectomy. We studied the effect of primary tumor resections tailored to the anatomical extent of the cancer with preservation of uninvolved structures in select patients with invasive penile squamous cell carcinoma. MATERIALS AND METHODS: A total of 30 patients between 39 and 82 years old were treated with unconventional conservative surgical excision of the primary penile lesion. More than 130 patients were excluded from the study because they were treated with partial or total penectomy, Mohs' surgery or more extensive surgery. The 30 patients underwent preoperative biopsy with careful mapping of the extent of the disease. Patient age, tumor extent and grade, operative details, outcome and length of followup were analyzed. RESULTS: Tumor size ranged from 1.5 to 8 cm. in diameter. Tumors were well differentiated in 19 patients, moderately differentiated in 5 and poorly differentiated in 6. A total of 17 patients underwent ilioinguinal lymphadenectomy, 12 of whom had pathologically positive lymph nodes. Inguinal radiation was used in 2 patients. Chemotherapy was given to 7 patients with extensive inguinal lymphadenopathy and to 2 of 5 with pathologically positive lymph nodes. Followup ranged from 12 to 360 months. A total of 21 patients had no evidence of disease at last followup. Tumor resection with no sacrifice of function was performed in 2 patients in whom 3 small recurrences developed. One patient with numerous tumors had 2 small recurrences, which were completely excised with no further recurrence. Of the 7 patients with advanced lymphadenopathy 5 and of 5 patients with pathologically positive lymph nodes at presentation 1 died of the cancer but had no local recurrence in the penis. CONCLUSIONS: In a minority of patients with anatomically suitable penile cancer conservative surgical techniques are safe and provide equal tumor control compared to conventional resections. The anatomical situation and tumor characteristics should dictate the choice of treatment for the primary penile lesion. Inguinal lymph nodes should be managed by appropriately established guidelines but should not influence the extent of primary penile lesion resection.

Retrograde vaginal methylene blue injection for localization of complex urinary fistulas.

BACKGROUND: Ureterovesical and vesicovaginal fistulae usually are easily diagnosed with standard techniques, including radiology, double-dye test, cystoscopy, and vaginal examination. In a few complex cases, however, the localization of the fistulous orifice may be extremely difficult. METHOD: We describe a novel technique of retrograde vaginal methylene blue testing that may assist in the proper localization of the fistulous opening. RESULTS: Our experience with one case each of ureterovesical and vesicovaginal fistula easily diagnosed with this method proves its efficacy, simplicity, and safety. CONCLUSION: This technique should be reserved for cases of urinary fistulae when all standard diagnostic methods have failed.