A risk-adjusted definition of biochemical recurrence after radical prostatectomy.

BACKGROUND: To determine whether a variable definition of biochemical recurrence (BCR) based on clincopathologic features facilitates early identification of patients likely to suffer from disease progression. The definition of BCR after radical prostatectomy (RP) bears important implications for patient counseling and management; however, there remains a significant debate regarding the appropriate definition. METHODS: The study cohort consisted of 3619 men who underwent RP for localized prostate cancer from 1989 to 2007, with data abstracted from the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry. Patients were stratified into three risk groups according to Cancer of the Prostate Risk Assessment post-Surgical (CAPRA-S) score. Three single threshold PSA cut-points for BCR were evaluated (PSA > or =0.05, > or =0.2 and > or =0.4 ng ml(-1)) as well as a variable cut-point defined by risk group. After reaching the cut-points, patients were followed for further PSA progression. RESULTS: The proportion of patients with BCR differed by cut-point and risk group, ranging from 7 to 37% (low risk), 22 to 58% (intermediate risk) and 60 to 86% (high risk). The positive-predictive value (PPV) for predicting further PSA progression was 49% for the PSA > or =0.05 ng ml(-1), 62% for the PSA > or =0.2 ng ml(-1), 65% for the PSA > or =0.4 ng ml(-1) and 68% for the risk-adjusted definition. Five-year progression-free survival was 39% for the risk-adjusted definition compared with 45-52% for the other definitions of BCR. CONCLUSIONS: These data suggest that a variable definition of BCR determined by clinicopathologic risk may improve the identification of early recurrence after RP without increasing the overdiagnosis of BCR. By using a risk-adjusted BCR definition, clinicians can better predict future PSA progression and more appropriately counsel patients regarding salvage therapies.

The use of mannitol in partial and live donor nephrectomy: an international survey.

PURPOSE: Animal studies have shown the potential benefits of mannitol as renoprotective during warm ischemia; it may have antioxidant and anti-inflammatory properties and is sometimes used during partial nephrectomy (PN) and live donor nephrectomy (LDN). Despite this, a prospective study on mannitol has never been performed. The aim of this study is to document patterns of mannitol use during PN and LDN. MATERIALS AND METHODS: A survey on the use of mannitol during PN and LDN was sent to 92 high surgical volume urological centers. Questions included use of mannitol, indications for use, physician responsible for administration, dosage, timing and other renoprotective measures. RESULTS: Mannitol was used in 78 and 64 % of centers performing PN and LDN, respectively. The indication for use was as antioxidant (21 %), as diuretic (5 %) and as a combination of the two (74 %). For PN, the most common dosages were 12.5 g (30 %) and 25 g (49 %). For LDN, the most common doses were 12.5 g (36.3 %) and 25 g (63.7 %). Overall, 83 % of centers utilized mannitol, and two (percent or centers??) utilized furosemide for renoprotection. CONCLUSIONS: A large majority of high-volume centers performing PN and LDN use mannitol for renoprotection. Since there are no data proving its value nor standardized indication and usage, this survey may provide information for a randomized prospective study.

Postchemotherapy ejaculatory azoospermia: fatherhood with sperm from testis tissue with intracytoplasmic sperm injection.

PURPOSE: To define the success of testis sperm extraction (TESE) and intracytoplasmic sperm injection (ICSI) in azoospermic men with a history of chemotherapy. PATIENTS AND METHODS: In a retrospective study, 23 men with ejaculatory azoospermia and a history of chemotherapy underwent TESE in a search for usable spermatozoa. In six patients cryopreserved tissue and in nine patients fresh tissue provided sperm for an ICSI cycle. Histologic analysis of the testis was performed in all patients. The presence or absence of sperm, fertilization rates with ICSI, and final outcomes of pregnancy were recorded. RESULTS: Spermatozoa were found on TESE in 15 (65.2%) of 23 men. On histopathology, the predominant pattern observed was Sertoli cell only (47.8%), followed by hypospermatogenesis (30.4%), mixed (17.4%), and late maturation arrest (4.3%). The fertilization rate was 65.2%, and ongoing/delivered pregnancies occurred in 30.8% of cycles. Six healthy boys and four healthy girls have been born to date. CONCLUSION: Men who are azoospermic and have had prior cytotoxic therapy make up a small subgroup of males with nonobstructive azoospermia. It is important to define and characterize this subgroup and better define their true fertility potential. Approximately two thirds of these men have retrievable testis sperm, which may be used with ICSI to have healthy offspring. This exciting avenue for paternity has heretofore not been available to such patients.

Laparoscopic nephrectomy for inflammatory renal conditions.

PURPOSE: Inflammatory and infectious renal conditions may result in severe perirenal fibrosis, making the laparoscopic approach challenging. The theoretical advantages of laparoscopy for managing inflammatory and infectious renal conditions have been questioned. We identified whether laparoscopy for inflammatory renal conditions is associated with higher morbidity than for other benign renal conditions. Furthermore, several technical modifications are discussed that may help to improve the outcome. MATERIALS AND METHODS: We retrospectively reviewed the records of all patients who underwent laparoscopic nephrectomy for inflammatory and infectious renal conditions between 1998 and 2000. The transperitoneal approach was used and specimens were removed after morcellation. Operative data were compared with those from a similar group of patients who underwent laparoscopic nephrectomy for other benign conditions. RESULTS: Laparoscopic nephrectomy done for inflammatory or infectious conditions in 12 cases and for other benign conditions in 9 matched cases was completed successfully in 10 (83%) and 9 (100%), respectively. In the inflammatory and benign groups mean blood loss plus or minus standard deviation was 155 +/- 163 and 59 +/- 23 ml. (p = 0.099), mean operative time was 284 +/- 126 and 226 +/- 62 minutes (p = 0.225), and mean postoperative hospital stay was 4.1 +/- 2 and 3 +/- 1 days (p = 0.157), respectively. CONCLUSIONS: Laparoscopic nephrectomy can be performed safely in most cases of inflammatory renal conditions. Although they were not statistically significant, a higher conversion rate and longer operative time should be expected. Early conversion may be required due to failure to progress. Similar advantages were observed in patients with inflammatory and other benign renal conditions via the laparoscopic approach.

Kidney morcellation in laparoscopic nephrectomy for tumor: recommendations for specimen sampling and pathologic tumor staging.

Laparoscopic nephrectomy is a novel approach for small renal tumors in selected patients; however, removal of the kidney through the small laparoscopic abdominal wall incision site requires the kidney to be morcellated into small fragments while still in situ. Morcellation presents two problems for the pathologist. First, guidelines for optimal sampling of morcellated fragments have not been described. Second, morcellation precludes complete pTNM tumor staging, in particular, tumor size, margins, and renal vein involvement. Based on our initial experience with 23 laparoscopic nephrectomies/nephroureterectomies (13 clinically suspected neoplasms, confirmed pathologically as renal cell carcinoma [RCC, n = 7], urothelial carcinoma of the renal pelvis [n = 3], angiomyolipoma [n = 1], and cystic nephroma [n = 1], and 10 clinically benign entities) and a conservative statistical model, we present a decision analysis model of various specimen sampling protocols that optimize cost, labor, or time to diagnosis (single vs sequential sampling). Using the tumor-to-kidney volume ratio (TKR), calculated from preoperative radiologic imaging and specimen gross weight, several specimen sampling algorithms were compared. For the average situation in which TKR is > or =0.15, the algorithm that most significantly optimizes cost and labor is one that initially samples 5% of the morcellated specimen. However, additional sampling may be required in one fourth of the cases. The optimal amount of sampled tissue may indeed be less than 5% because this assumes no suspicious tissue is grossly visible and in all our cases of RCC grossly visible tumor was identified. Additional nomograms for a spectrum of TKR, sampling success, and cost are presented to allow pathologists their own discretion in determining optimal sampling of the morcellated kidney. Tumor staging is severely limited by morcellation. Tumor size, renal capsule involvement, and renal vein involvement cannot be fully pathologically evaluated for RCC, whereas invasion cannot be definitively assessed for urothelial carcinoma of the renal pelvis. Knowledge of the radiologic features (lesion size, capsule, and vein involvement) is important in sampling and staging morcellated kidneys removed laparoscopically.

Novel method of assessing surgical margin status in laparoscopic specimens.

OBJECTIVES: To develop a novel method of inking laparoscopic specimens before piecemeal extraction to evaluate the surgical margins. METHODS: Methylene blue, indigo carmine, and India ink were tested in vitro on cadaveric bovine kidneys before manual morcellation in laparoscopic retrieval bags, and subsequently in pigs in vivo undergoing laparoscopic nephrectomy. Tissue fragments were examined both grossly and microscopically after routine histologic processing. On the basis of the findings in these experiments, we used India ink clinically in 4 cases of laparoscopic nephrectomy and adrenalectomy for suspected tumor and assessed the ability to indicate specimen margins grossly and microscopically. RESULTS: Methylene blue and India ink were the substances that best covered the surface of the surgical specimen completely, were best retained on the tissue, and were most easily washed from the retrieval bag. Gross inspection of the morcellated specimens easily distinguished the inked pieces, signifying tissue present at the surgical margin, from the uninked pieces. During morcellation, neither contamination of central tissue with ink nor leakage of ink from the bag occurred. India ink consistently endured fixation, embedding, and sectioning, with the black, inked margins of the specimen visible microscopically. CONCLUSIONS: Application of India ink before laparoscopic organ morcellation specifically marks the margins of the specimen. This technique allows pathologic determination of the surgical margin status, as well as fractionation of the tissue fragments, and addresses a criticism of organ morcellation. These improvements in the pathologic analysis of laparoscopically excised specimens may obviate the need for intact organ removal.

Minichromosome maintenance protein 2 expression in prostate: characterization and association with outcome after therapy for cancer.

The minichromosome maintenance (MCM) proteins are highly conserved proteins essential for initiating and regulating eukaryotic DNA replication. Recent studies have demonstrated the potential use of MCM proteins as markers of proliferation. We characterized the pattern of Mcm 2 staining in benign and malignant prostate tissues and examined the role of Mcm 2 expression in disease-free survival after surgery in men with localized prostate cancer. Tumors from 92 patients who underwent radical prostatectomy for prostate cancer (median follow-up of 54 months) were examined for Mcm 2 expression by immunohistochemistry using a monoclonal antibody. Prostate tissue from five men without histopathological evidence of prostate cancer was also stained for Mcm 2. Mcm 2 expression was quantified by calculating a labeling index, and patients were grouped according to degree of staining. An analysis of the association between Mcm 2 expression with traditional clinicopathological characteristics of prostate cancer was carried out. A Cox proportional hazards analysis was performed to determine whether Mcm 2 staining was a significant independent predictor of disease-free survival. Mcm 2 expression is low (<2%) and limited to the basal cell layer in nonmalignant prostate glands. Mcm 2 expression is consistently increased in malignant glands and is significantly associated with disease-free survival in univariate (P = 0.002) and multivariate (P = 0.01) analyses. Patients with high Mcm 2 expression exhibited shorter disease-free survival. Mcm 2 expression was not associated with any traditional clinical or pathological factors and therefore is an independent predictor of survival in these patients with prostate cancer. These data support evidence that Mcm 2 may serve as a novel proliferation marker in the prostate. Mcm 2 expression is an independent predictor of disease-free survival after definitive local therapy and has potential as a molecular marker for clinical outcome in prostate cancer.

Impaired spermatogenesis in men with congenital absence of the vas deferens.

It is generally assumed that men with congenital bilateral absence of the vas deferens (CBAVD) have azoospermia because of obstruction and that sperm production is normal. This study examines spermatogenesis in men with CBAVD to assess the validity of this assumption. We identified all men with CBAVD who had undergone either a diagnostic or therapeutic fertility procedure. Procedures included diagnostic biopsy, testis fine needle aspiration (FNA) mapping, microscopic epididymal sperm aspiration (MESA), and testis sperm extraction (TESE). Among 33 CBAVD men, 18 underwent testis biopsy, 27 had MESA/TESE, and 10 had FNA mapping. On evaluation of these procedures, normal spermatogenesis was present in 29 men. Four men (12%) demonstrated impaired spermatogenesis. One patient had FNA testis cytology consistent with late maturation arrest, another demonstrated hypospermatogenesis on biopsy and low sperm yield by MESA, and two patients had pure Sertoli cell only histology on biopsy. Aetiologies for impaired spermatogenesis included varicocele and underlying genetic abnormalities. Although patients with CBAVD are assumed to have normal spermatogenesis and infertility due simply to obstruction, the potential for concomitant defects in sperm production exists. A clinical suspicion of testis failure should prompt further diagnostic evaluation of spermatogenesis prior to sperm retrieval. In addition, genetic counselling should be offered and testing for genetic lesions, including cystic fibrosis gene mutations and/or variants, Y chromosome microdeletions, and karyotype abnormalities, should be considered.

Testicular fine-needle aspiration in infertile men: correlation of cytologic pattern with biopsy histology.

Open testicular biopsy is the standard method for histopathologic assessment of spermatogenesis. The need for testis biopsy has been questioned with the increased success of minimally invasive techniques such as fine-needle aspiration (FNA) mapping. This study examines whether FNA can provide cytologic information equivalent to histologic patterns by correlating diagnoses from testis FNA cytology with biopsy histology. Men (n = 87) who had undergone both diagnostic FNA mapping and open testis biopsy in the evaluation of infertility were identified. Biopsies were assessed by recognized histologic patterns of normal, hypospermatogenesis, early and late maturation arrest, and Sertoli cell only. FNA cytologic specimens were examined for adequacy and were classified similarly. Mixed patterns were also identified. The correlation between the two methods was 94%, with no differences among the different histologies. Discrepancies between cytology and histology were primarily the result of inadequate sampling and evidence of mixed patterns on FNA mapping. FNA cytology is a minimally invasive method of obtaining testicular tissue for diagnostic purposes. These data demonstrate that FNA cytology can evaluate accurately all classically defined histologic types, and may have the potential to replace testis biopsy in the assessment of spermatogenesis.

Laparoscopic live donor nephrectomy at the University of California San Francisco.

Laparoscopic donor nephrectomy is quickly becoming the preferred technique for kidney retrieval, since it removes many of the disincentives of kidney donation. Our experience at UCSF has confirmed that the procedure is safe, with excellent donor recovery. The transplanted kidney appears to function as well as any kidney retrieved using an open technique, at least in the short-term. Development of a successful laparoscopic donor program is best done initially with a team approach, utilizing the skills of an advanced laparoscopic surgeon, and with careful patient selection. With time, the technique can be done well by properly trained transplant surgeons with basic laparoscopic skills, with or without a hand-assist technique. As experience grows, this procedure can be applied to virtually every potential donor, and hopefully will improve live kidney donation rates.

Local therapy for prostate-specific antigen recurrence after definitive treatment.

Disease recurrence after local therapy for prostate cancer is increasingly common, most often with detectable or rising prostate-specific antigen (PSA) the earliest sign. Analysis of clinical and pathological factors can help determine which patients are at risk for treatment failure, while PSA characteristics and imaging studies can localize site of recurrent disease and identify men who may benefit from salvage therapy. Local treatment options include radiation therapy (external beam and brachytherapy) and cryoablation for patients who have undergone prostatectomy, and surgery, brachytherapy, and cryoablation for patients who have received radiotherapy. Novel treatment modalities are under investigation and may improve success of local salvage therapy while minimizing morbidity. Prostate Cancer and Prostatic Diseases (2001) 4, 20-27

Is it necessary to do staging pelvic lymph node dissection for T1c prostate cancer?

The necessity of pelvic lymph node dissection has been questioned in recent years as a result of improved pre-treatment staging based on clinical and pathologic factors. Accurate evaluation of nodal status allows rational selection of therapy and improved outcomes. Nevertheless, lymph node dissection may play a role even in patients with low stage disease (clinical T1c) despite an overall low risk for metastases. Herein we discuss recent advances in the evaluation of lymph nodes in stage T1c prostate cancer with respect to accurate prediction, radiologic imaging, molecular characterization, and operative considerations.

Relationship between classic histological pattern and sperm findings on fine needle aspiration map in infertile men.

Systematic testis fine needle aspiration (FNA) mapping has been proposed as an adjunctive or alternative diagnostic procedure to biopsy to determine the presence of spermatozoa within infertile testes. This study related testis histology to the global presence or absence of spermatozoa in the same testes determined by FNA cytology. Testis biopsies and FNA mapping were performed in 87 infertile, azoospermic men. A mean of 1.3 biopsies and 14 FNA sites were taken per patient. Biopsies were assessed by recognized histological patterns of normal, Sertoli cell-only, hypospermatogenesis, early and late maturation arrest, sclerosis as well as mixed patterns that included at least two of these histologies. FNA cytological specimens were assessed for sperm presence by an experienced cytologist. Overall, spermatozoa were found by FNA mapping in 52% of patients. A comparison of histology and FNA findings revealed that pure patterns of Sertoli cell-only and early maturation were associated with a very poor likelihood of sperm detection (4-8%). In contrast, patients with other pure pattern histologies or mixed patterns had high rates of FNA sperm detection (77-100%). Similar to reported testicular sperm extraction (TESE) findings, sperm detection with FNA shows wide variation depending on testis histology. Unlike most TESE reports, however, some histological patterns generally reflect a more global testicular dysfunction and poorer likelihood of sperm identification, suggesting the possibility that these phenotypes have a genetic origin. Systematic testis sampling with FNA offers additional geographical information about spermatogenesis that routine biopsies lack and can further guide couple decision-making in severe male factor infertility.

When is pelvic lymph node dissection necessary before radical prostatectomy? A decision analysis.

PURPOSE: In recent years the role of pelvic lymph node dissection before or at radical prostatectomy has been questioned. We compared the outcome of performing or omitting pelvic lymph node dissection in patients undergoing radical retropubic prostatectomy by formal decision analysis. MATERIALS AND METHODS: We created a decision tree for patients undergoing radical retropubic prostatectomy that accounts for all possible branch points and outcomes. Outcome probabilities applied to the model were derived from published data. Utility values were determined for each outcome state by a panel of experts. Decision analysis was done using decision analysis computer software. Sensitivity analysis was performed to determine which elements in the model were most important and to calculate threshold values. RESULTS: Using probability data from the literature and our assigned outcome values, decision analysis initially favored omitting pelvic lymph node dissection. Sensitivity analysis revealed that the threshold values for the incidence of positive lymph nodes and the sensitivity of lymph node dissection and frozen section analysis at which outcomes were equivalent were 18% and 80%, respectively. Analysis was insensitive to the pelvic lymph node dissection complication rate. CONCLUSIONS: We performed formal decision analysis to determine the incidence of lymph node metastasis below which pelvic lymph node dissection is not warranted at radical retropubic prostatectomy. Our results suggest that lymph node dissection is unnecessary in the subset of patients in which the risk of lymph node involvement is less than 18%.

Hematospermia as the presenting symptom of metastatic malignant melanoma of unknown primary origin.

The presence of blood in the ejaculate is alarming to patients and may arise from many sources in the genitourinary tract. Fortunately, hematospermia is rarely due to underlying malignancy and only necessitates further evaluation with continued symptoms. We report a case of persistent hematospermia in a man with human immunodeficiency virus caused by metastatic malignant melanoma to both seminal vesicles. The evaluation included pelvic magnetic resonance imaging and transrectal ultrasound-guided biopsy. Metastases to the brain were subsequently discovered, but a primary source for the melanoma could not be identified. This is the first reported case of isolated involvement of the seminal vesicles with malignant melanoma and underscores the potential for serious disease presenting as hematospermia.

Renal trauma: indications and techniques for surgical exploration.

Injury secondary to trauma has become increasingly common in modern society. In the United States, in excess of 55 million trauma patients are evaluated each year, and trauma is the leading cause of mortality in people under the age of 40 years. Of the patients with abdominal trauma, approximately 10% have an injury to the urinary tract. Renal injury, occurring in 1-5% of all traumas, is due primarily to blunt trauma. Advances in the imaging and staging of renal trauma as well as in treatment strategies have decreased the need for surgical intervention and increased renal preservation. Nevertheless, no consensus exists regarding indications and techniques for renal exploration. The goals of treatment include accurate staging, maximal preservation of renal function, and minimal complications. We discuss our current approach in the management of renal trauma.

Testis sperm extraction and intracytoplasmic sperm injection guided by prior fine-needle aspiration mapping in patients with nonobstructive azoospermia.

OBJECTIVE: To evaluate intracytoplasmic sperm injection (ICSI) outcomes in a cohort of men with nonobstructive azoospermia who underwent prior fine-needle aspiration (FNA) "maps" to localize sperm and guide testis sperm extraction (TESE). DESIGN: Retrospective clinical study. SETTING: University-based infertility practice. PATIENT(S): A consecutive cohort of 19 infertile, azoospermic men. INTERVENTION(S): Couples underwent IVF-ET in which TESE procedures were informed and directed by prior FNA maps of the testis. MAIN OUTCOME MEASURE(S): Sperm retrieval and pregnancy rates. RESULT(S): In 21 IVF-ET and ICSI cycles, sufficient sperm for all oocytes were retrieved in 20 TESE attempts (95%). A mean of 3.1 biopsies per patient were required, with an average size of 72 mg. Mean operative time for the TESE procedure was 88 minutes. Overall, the two-pronuclear fertilization rate was 66%; ongoing clinical pregnancies were obtained in 10 of 21 initiated cycles (48%). CONCLUSION(S): In an effort to reduce IVF-ET cancellation rates in cases of nonobstructive azoospermia, diagnostic testis FNA can define those patients who are good candidates for TESE. It also directs sperm retrieval and minimizes tissue removal from nonobstructed testes.

Skin graft reconstruction of chronic genital lymphedema.

OBJECTIVES: We present a simple, reliable method of scrotal and penile reconstruction yielding satisfactory cosmetic and functional results for patients with disabling chronic genital lymphedema. METHODS: Nine patients were treated with wide excision of the affected genital skin and subsequent coverage of exposed areas with split-thickness skin grafts in a single-stage procedure. RESULTS: All patients have had excellent cosmetic results without recurrence of genital lymphedema or compromise of sexual function postoperatively. CONCLUSIONS: Single-stage reconstruction for idiopathic genital lymphedema by radical skin excision and split-thickness skin grafting provides gratifying functional and cosmetic results.