Biology and natural history of prostate cancer and the role of chemoprevention.

Androgens not only play an important role in the development and function of the prostate but they are also intimately involved in the development and progression of prostate cancer (PCa). Within the prostate, testosterone is converted to the more potent androgen dihydrotestosterone (DHT) via the action of 5α-reductase enzymes. DHT is the primary prostatic androgen and promotes the growth and survival of normal, hyperplastic and malignant prostate tissues. Throughout the different stages of PCa [prostatic intraepithelial neoplasia (PIN), localised, recurrent, and metastatic] there is an increase in expression of 5α-reductase enzymes, particularly in localised high-grade carcinoma. Specifically inhibiting 5α-reductase may reduce the production of DHT in the prostate while maintaining other endogenous hormone levels. Clinical studies have shown significant PCa risk reduction by blocking this pathway with 5α-reductase inhibitors (5ARIs). However, this comes at a risk, albeit low, with sexual side effects, gynaecomastia and cardiac failure. In addition, one study has shown a slight, but significant, risk of high-grade PCa. The currently available evidence does not support the routine use of 5α-reductase inhibitors to prevent PCa in the general population. It could, however, be considered as an individual option for high-risk or concerned patients with appropriate education from the prescribing provider.

Extraperitoneal inguinoscrotal herniation of the ureter: a rare case of recurrence after hernia repair.

Inguinoscrotal herniation of the ureter is a rare finding with the potential for serious surgical complications. Two anatomic forms are defined. In the more common paraperitoneal variant, the herniating peritoneal sac drags the ureter and sometimes other abdominal structures with it. The uncommon variant--extraperitoneal inguinal herniais without a peritoneal sac and consists of the ureter and fat tissue. We report a case of extraperitoneal inguinoscrotal hernia possibly due to a prior inguinal hernia repair.

Incidence, risk profile and morphological pattern of venous thromboembolism after prostate cancer surgery.

BACKGROUND: Venous thromboembolism (VTE) is the most common non-surgical complication after major pelvic surgery. Little is known about the risk factors or the time of development of postoperative venous thrombosis. METHODS: A cohort of 523 consecutive patients undergoing radical prostatectomy with lymphadenectomy was prospectively assessed by complete compression ultrasound at days -1, +8 and +21. RESULTS: Complete data were available in 415 patients, while four patients had VTE before surgery and were excluded from the analysis. In the remaining 411 patients, 71 VTE events were found in 69 patients (16.8%). Most were limited to calf muscle veins (56.5%), followed by deep calf vein thrombosis (23.2%), proximal deep vein thrombosis (DVT, 14.5%) and pulmonary embolism (PE, 5.8%). Of the 14 patients with proximal DVT/PE, 11 patients (78.6%) developed VTE between days 8 and 21. Risk factors for VTE were a personal history of VTE (OR 3.0), pelvic lymphoceles (LCs) impairing venous flow (OR 2.8) and necessity of more than two units of red blood cells (OR 2.6). CONCLUSION: Venous thromboembolism is common after radical prostatectomy. A significant proportion develops after day 8, suggesting that prolonged heparin prophylaxis should be considered. Since LCs with venous flow reduction result in higher rates of VTE, hemodynamically relevant lymphoceles should be surgically treated.

Lymph node disease after radical prostatectomy.

Most patients with lymph node involvement at radical prostatectomy are destined to experience disease progression. Since the detection rate of lymph node metastases depends on the extension of lymphadenectomy, comparison between series may be biased and there is no generally accepted treatment approach. Although one small randomized study demonstrated a survival benefit for patients receiving immediate hormonal treatment compared with treatment onset at clinical progression, in patients with minimal lymph node involvement the benefit of immediate treatment is uncertain. It is possible that treatment onset at PSA relapse is sufficient in such cases thus sparing side effects and costs of hormonal treatment. The role of adjuvant radiotherapy is unclear in patients with lymph node involvement at radical prostatectomy. Since spread into the lymph nodes in most cases indicates systemic disease, local measures only are unlikely to cure those patients. Possibly, in select cases, adjuvant radiotherapy may improve local control and maintain quality of life, even if no survival benefit may be expected. Overall, there is a need to enroll patients with lymph node involvement at radical prostatectomy onto clinical studies to improve the body of knowledge on optimal management in these cases.

Early changes of oxalate and calcium urine excretion in those with calcium oxalate stone formation after extracorporeal shock wave lithotripsy.

OBJECTIVES: To determine the extent of transient changes of tubular function in idiopathic calcium-oxalate (CaOx) stone-bearing patients after extracorporeal shock wave lithotripsy (ESWL), calcium and oxalate excretion were measured before and after ESWL. METHODS: In 22 patients with renal CaOx stones, the plasma values and urine excretion of creatinine, calcium, oxalate, magnesium, and citrate were measured before and on days 1 and 2 after ESWL under conditions of a standardized diet. Overnight urine collection for an 8-hour period was used to measure the urine excretion, and the values were extrapolated to a 24-hour period. For calculation of the urine ion activity, the AP(CaOx) index EQ(s) and the CaOx risk index were used. RESULTS: After ESWL, hyperoxaluria was noted in 10 patients compared with 2 before ESWL. Hypercalciuria was seen in 11 patients after ESWL compared with 3 before. Combined hyperoxaluria and hypercalciuria was found in 7 patients after ESWL compared with 1 before. Both the oxalate/creatinine and calcium/creatinine ratios were significantly increased after ESWL. The AP(CaOx) index EQ(s) and the CaOx risk index were significantly increased after ESWL in patients with increased post-ESWL calcium and/or oxalate excretion. CONCLUSIONS: Increased calcium and/or oxalate excretion can be seen in patients with CaOx stones early after ESWL. This increased excretion of lithogenic substances represents an increased risk of fragment apposition after ESWL for the group with a significantly increased AP(CaOx) index EQ(s) and CaOx risk index. Therefore, prophylactic measures in patients at risk early after ESWL might be warranted to prevent possible recurrent stone formation.

Measurement of free radicals and NO by chemiluminescence to identify the reperfusion injury in renal transplantation.

Oxygen free radicals are generated during the reperfusion of ischaemic organs. Several experimental studies have demonstrated that the damage produced by reperfusion can be prevented by a scavenger of free radicals. Furthermore, a significantly improved 5 year graft survival rate after cadaveric renal transplantation has been reported in patients treated with scavengers of free radicals (Land et al., 1993). Therefore, a question remains to be answered: whether a routine monitoring of the radical-mediated reperfusion injury with renal transplantation is useful, and whether there is a necessity for a generalized protective treatment in transplant patients. In a prospective trial, we evaluated a group of eight patients during and after renal cadaveric transplantation (three men, five women), using the chemiluminometric measurement of serum free radicals and NO. The serum quantities of free radicals and NO were significantly increased after reperfusion of the transplant kidney (p < 0.02). The mean time of noticeably increased levels of serum free radicals was 4.8 +/- 1.2 h after reperfusion. The results thus showed an increased liberation of free radicals in the peripheral blood of transplant recipients as possible evidence of free radicals-mediated reperfusion injury in renal transplantation. The generation of free radicals measured by chemiluminescence allow a controlled therapy to decrease the generation of free radicals with antioxidants during the early transplantation period e.g. in older recipients.

Relationship of comorbidity, age and perioperative complications in patients undergoing radical prostatectomy.

OBJECTIVES: To investigate the prevalence and distribution of comorbidity and its association with perioperative complications in patients undergoing radical prostatectomy (RPE). METHODS: In 431 unselected RPE patients, the American Society of Anesthesiologists Physical Status classification (ASA-PS), the New York Heart Association classification of cardiac insufficiency (NYHA), the classification of angina pectoris of the Canadian Cardiovascular Society (CCS), height, weight, the body mass index (BMI), and the number of concomitant diseases (NCD) were assessed and related to perioperative cardiovascular complications. RESULTS: In RPE patients less than 70 years old, comorbidity rose nearly continuously with increasing age. However, after reaching an age of 70 years, the proportion of NYHA-0 patients increased (60-64 years, 86%; 65-69 years, 85%; >or=70 years, 87%). Furthermore, the severe comorbidities decreased in patients selected for RPE aged 70 or more years. There was a nonsignificant trend towards higher comorbidity in patients with perioperative cardiovascular complications. CONCLUSIONS: These data suggest that documentation of the distribution of ASA-PS, CCS, NYHA and of concomitant diseases might be helpful to characterize the general health status and the degree of selection of prostate cancer treatment populations especially in series with a high portion of patients aged 70 or more years. Concerning perioperative complications, the individual predictive value of comorbidity seems to be poor in the radical prostatectomy setting.

Durable complete remission of metastatic sarcomatoid carcinoma of the bladder with cisplatin and gemcitabine in an 80-year-old man.

A patient with a durable, complete, local and pulmonary remission of a metastatic sarcomatoid carcinoma of the bladder treated with gemcitabine and cisplatin is presented. Sarcomatoid carcinoma arising in the bladder is a rare and notoriously aggressive variant of urothelial carcinoma for which an effective systemic treatment has not been reported up to now.

The treatment of primary urethral carcinoma--the dilemmas of a rare condition: experience with partial urethrectomy and adjuvant chemotherapy.

BACKGROUND: Primary urethral carcinoma is a very rare condition, and no large-scale experience with such cases has been published. Treatment will therefore have to follow rules established for the treatment of similar conditions. PATIENTS: Six cases of primary urethral carcinoma (5 male, 1 female) who had been treated at our institution between 1995 and 1999 were retrospectively analyzed. In 3 male cases, a primary urothelial carcinoma of the distal urethra was treated by distal urethrectomy only. In 3 other cases with locally advanced tumors and/or lymph node metastases surgical treatment was followed by adjuvant cisplatinum-containing chemotherapy. RESULTS: In the 3 cases with distal urethral carcinoma, partial urethrectomy with preservation of the penis resulted in cure, with a follow-up of 12-71 months. In the cases with advanced disease, adjuvant chemotherapy after surgery has resulted in complete remissions in all 3 cases, with a follow-up of 4-47 months at present. CONCLUSIONS: In localized, noninvasive carcinoma of the distal male urethra, partial urethrectomy seems adequate and the avoidance of penile amputation justified. In advanced cases, after local excision and lymphadenectomy adjuvant chemotherapy which by necessity must follow the guidelines established for the treatment of other urothelial or squamous cell malignancies seems to be beneficial.

Etiologic factors in soft tissue sarcomas.

Soft tissue sarcomas account for about 1% of all malignancies. The increase in incidence of soft tissue sarcomas during the recent decades may predominantly be attributed to AIDS-related Kaposi's sarcoma; when this tumor is excluded, conclusive evidence for an age-adjusted increase is lacking. Beside the well investigated role of the human immunodeficiency virus 1 (HIV-1) and the human herpesvirus 8 (HHV-8) in the tumorigenesis of AIDS-related Kaposi's sarcoma and several inherited disorders, considerable evidence support a relationship between occupational chemicals as vinyl chloride, phenoxyacetic acid herbicides, chlorphenols, dioxin, medicinal measures as Thorotrast exposure and therapeutic irradiation, and the development of soft tissue sarcoma. Hormones and chronic repair processes are further probably sarcoma-promoting factors. Considering the rarity of soft tissue sarcomas despite the vast portion that soft tissues comprise in the human body, additional knowledge on the tumorigenesis of soft tissue sarcomas might considerably contribute to the understanding of the etiologic pathways of malignant tumors in humans.

Liposarcoma of the diaphragm: CT and sonographic appearances.

Malignant tumors arising from the diaphragm are exceedingly rare. We describe the first case, to our knowledge, of a primary diaphragmatic liposarcoma and demonstrate computed tomographic and sonographic findings.

Morbidity and discomfort of ten-core biopsy of the prostate evaluated by questionnaire.

Transition zone biopsies have been found to increase the detection rates of cancer of the prostate in patients with negative digital rectal examination. There are however no data available whether the higher biopsy rate is associated with greater morbidity. The present study was therefore designed to evaluate the complication rate of extended sextant biopsy. In this prospective study, 162 consecutive patients who presented for prostatic evaluation were included. After starting prophylactic antibiotic treatment 48 h prior to the procedure, transrectal ultrasound-guided core biopsies were obtained from each lobe: three each from the peripheral zone (apex, mid-zone and base) and two from the transition zone of each prostatic lobe. In all patients a questionnaire was obtained 10-12 days after the procedure. Major complications occurred in 3 patients. In 2 of the 3 cases major macroscopic hematuria was treated by an indwelling catheter for 1 or 2 days and 1 patient developed fever >38.5 degrees C for 1 day. Minor macroscopic hematuria was present in 68.5% of the patients. In 17.9% of these cases, the hematuria lasted for more than 3 days. Hematospermia was observed in 19.8% and minor rectal bleeding occurred in 4.9%. Ten-core biopsies did not lead to an increase in adverse effects or complications when compared to the results of sextant biopsies reported in the literature.

Malignant fibrous histiocytoma of the ileum at a site of previous surgery: report of a case.

Sarcomas rarely arise in the intestinum, and leiomyosarcoma represents the majority of cases. With only seven cases reported in the available English literature up to now, malignant fibrous histiocytoma of the small intestine is exceedingly rare. Moreover, follow-up data are almost completely unavailable. We present herein the unique case of a malignant fibrous histiocytoma arising in a postoperatively adherent intestinal loop. To the best of our knowledge, this is the first such case ever to be described. The clinical history and the intraoperative findings suggested that chronic postoperative repair processes might have been a promoting factor in the tumorigenesis of this neoplasm, on the analogy of malignant fibrous histiocytoma arising at different sites. The patient recovered well but 9.5 years after surgical removal, a solitary recurrent tumor developed in the urinary bladder and progressed rapidly, highlighting the need for long-term, possibly life-long, surveillance of patients with this rare type of intestinal cancer.

Is systematic sextant biopsy suitable for the detection of clinically significant prostate cancer?

BACKGROUND: The optimal extent of the prostate biopsy remains controversial. There is a need to avoid detection of insignificant cancer but not to miss significant and curable tumors. In alternative treatments of prostate cancer, repeated sextant biopsies are used to estimate the response. The aim of this study was to investigate the reliability of a repeated systematic sextant biopsy as the standard biopsy technique in patients with significant tumors which are being considered for curative treatment. METHODS: Systematic sextant biopsy was performed in vitro in 92 radical prostatectomy specimens. Of these patients, 81 (88.0%) had palpable lesions. RESULTS: Of the 92 investigated patients, 70 (76.1%) had potentially curable pT2-3pN0 prostate cancers. In these patients, the cancer was detected only in 72.9% of cases by a repeated in vitro biopsy. In the pT2 tumors, there was a detection rate of only 66.7%. CONCLUSIONS: This study underlines the fact that a considerable number of significant and potentially curable tumors remain undetected by the conventional sextant biopsy. A negative sextant biopsy does not rule out significant prostate cancer.

Favorable long-term outcome in adult genitourinary low-grade sarcoma.

OBJECTIVES: To report our experience treating sarcomas in 20 consecutive patients. METHODS: Pretreatment and follow-up data were obtained from 20 adult patients consecutively treated between 1992 and 1998 for primary or locally recurrent genitourinary sarcoma. RESULTS: Eight patients (40%) were classified as having high-grade and 12 (60%) low-grade disease. Except for 3 patients, the primary treatment was surgery alone. The median follow-up was 52 months. The actuarial disease-specific 5-year survival rate was 84% in all patients and was 100% for patients with Memorial Sloan Kettering Cancer Center (MSKCC) Stages 1-2 and 54% in MSKCC Stages 3-4. The disease-specific survival was significantly better in low-grade tumors (log-rank test, P = 0.0063) and inguinal-scrotal tumors (P = 0.019), tumors 5 cm or less (P = 0.039), and MSKCC Stages 1-2 tumors (P = 0.0035). CONCLUSIONS: The results of this study with a high proportion of low-grade, low-stage, and inguinal-scrotal sarcomas demonstrate the favorable prognosis of these subgroups.

Mucoepidermoid penile carcinoma: clinical, histologic, and immunohistochemical characterization of an uncommon neoplasm.

We report a case of a mucoepidermoid penile carcinoma. The specimen was studied by immunohistochemistry and DNA cytometry. Mucoepidermoid and adenosquamous penile carcinoma are exceedingly rare variants of penile cancer, with very little follow-up data available. To evaluate the possible prognostic significance of these differentiation patterns, it is necessary to document more cases of this unusual tumor entity.