Fray F. Marshall

The Management of Renal Angiomyolipoma

Revue des cas de la litterature mondiale et de 13 cas personnels. Un schema therapeutique systematique est propose base a la fois sur la taille de la tumeur et les symptomes

The natural history of renal angiomyolipoma

Of 35 patients with 48 angiomyolipomas 24 patients were followed clinically to determine the natural history of angiomyolipoma. Average patient age at presentation was 50 years (range 17 to 74) and of the patients 94% were women, 17% had tuberous sclerosis and 25% overall had bilateral disease. The patients could be divided into 2 distinct groups based on tumor size of 4 cm. or less and greater than 4 cm. Those with tumors less than 4 cm. were less likely to be symptomatic (24%) and patients with angiomyolipomas greater than 4 cm. were more often symptomatic (52%). No surgery was required for tumors less than 4 cm. but for 30% of the tumors greater than 4 cm. surgical intervention was necessary. Unlike any previously reported large series this study included radiological and historical followup available for 24 patients with angiomyolipoma with a mean followup time of 4 years (range 0.5 to 14). Moreover, to our knowledge we report for the first time documented growth during the study period of 27% of angiomyolipomas less than 4 cm. (4 of 15 tumors) and 46% of angiomyolipomas greater than 4 cm. (6 of 13 tumors). All patients with tumors less than 4 cm. were asymptomatic and only 1 required surgery. In contrast, tumors greater than 4 cm. were more frequently symptomatic (46%) and required surgery (54%). Patients with tuberous sclerosis and angiomyolipomas were distinctly different from patients with angiomyolipoma only, since they tended to present at a younger age, had a higher incidence of bilateral renal involvement, were more symptomatic, had larger tumors that were more likely to grow, and frequently required surgery. Based on this study, a modified approach to the current management of angiomyolipoma is recommended.

Expression profiling of renal epithelial neoplasms: a method for tumor classification and discovery of diagnostic molecular markers.

The expression patterns of 7075 genes were analyzed in four conventional (clear cell) renal cell carcinomas (RCC), one chromophobe RCC, and two oncocytomas using cDNA microarrays. Expression profiles were compared among tumors using various clustering algorithms, thereby separating the tumors into two categories consistent with corresponding histopathological diagnoses. Specifically, conventional RCCs were distinguished from chromophobe RCC/oncocytomas based on large-scale gene expression patterns. Chromophobe RCC/oncocytomas displayed similar expression profiles, including genes involved with oxidative phosphorylation and genes expressed normally by distal nephron, consistent with the mitochondrion-rich morphology of these tumors and the theory that both lesions are related histogenetically to distal nephron epithelium. Conventional RCCs underexpressed mitochondrial and distal nephron genes, and were further distinguished from chromophobe RCC/oncocytomas by overexpression of vimentin and class II major histocompatibility complex-related molecules. Novel, tumor-specific expression of four genes-vimentin, class II major histocompatibility complex-associated invariant chain (CD74), parvalbumin, and galectin-3-was confirmed in an independent tumor series by immunohistochemistry. Vimentin was a sensitive, specific marker for conventional RCCs, and parvalbumin was detected primarily in chromophobe RCC/oncocytomas. In conclusion, histopathological subtypes of renal epithelial neoplasia were characterized by distinct patterns of gene expression. Expression patterns were useful for identifying novel molecular markers with potential diagnostic utility.

Laparoscopic radical nephrectomy: cancer control for renal cell carcinoma.

PURPOSE We evaluated the clinical efficacy of laparoscopic versus open radical nephrectomy in patients with clinically localized renal cell carcinoma. MATERIALS AND METHODS Between 1991 and 1999, 67 laparoscopic radical nephrectomies were performed for clinically localized, stages cT1/2 NXMX, pathologically confirmed renal cell carcinoma. During this period 54 patients who underwent open radical nephrectomy with pathologically confirmed stages pT1/2 NXMX disease were also identified. Medical and operative records were retrospectively reviewed and telephone followup was done to assess patient status. RESULTS In the laparoscopic and open groups average tumor size was 5.1 (range 1 to 13) and 5.4 cm. (range 0.2 to 18), respectively, which was not statistically significant. No patient had laparoscopic port site, wound or renal fossa tumor recurrence in either group. All patients were followed at least 12 months. In the laparoscopic group 2 cancer specific deaths occurred at a mean followup of 35.6 months. In the open group there were 2 cancer specific deaths and 3 cases of disease progression at a mean followup of 44 months. Kaplan-Meier disease-free survival and actuarial survival analysis revealed no significant differences in the laparoscopic and open radical nephrectomy groups. Also, no differences were noted in the complication rate. CONCLUSIONS Laparoscopic radical nephrectomy is an effective alternative for localized renal cell carcinoma when the principles of surgical oncology are maintained. Initial data show shorter patient hospitalization and effective cancer control with no significant difference in survival compared with open radical nephrectomy.

Selection of men at high risk for disease recurrence for experimental adjuvant therapy following radical prostatectomy

OBJECTIVES Following surgery, men with recurrent prostate cancer have an isolated elevation in serum prostate-specific antigen (PSA) well in advance of measurable metastatic disease. Rational patient selection for new forms of adjuvant therapy, for example, gene therapy, is imperative. METHODS In a retrospective study of two cohorts, we used proportional hazards regression analysis to develop and validate a multifactor model for identifying men who are at high risk of cancer recurrence. The model cohort consisted of 216 men with clinical Stage T2b and T2c treated by 1 urologist. The validation cohort consisted of 214 men with Stage T2b and T2c disease. RESULTS A model for log relative risk, Rw, used serum PSA with a sigmoidal transformation (PSAST), radical prostatectomy Gleason score (GS), and pathologic stage (PS) as specimen confined or nonspecimen confined: Rw = (PSAST x 0.06) + (GS x 0.54) + (PS x 1.87). Recurrence risk categories were determined as low risk if Rw is less than 4.0, intermediate risk if it is 4.0 to less than 5.75, and high risk if Rw is more than 5.75. The observed Kaplan-Meier actuarial analysis of the three risk groups correlated well with the predictions determined for the model cohort. We then validated this model independently using a second cohort of 214 men with similar age, stage, and grade treated by 3 different urologists at two different institutions. CONCLUSIONS The recurrence rates for men in the high-risk group are similar to those for men with positive lymph nodes and justifies exploration of experimental adjuvant therapy within this group using this model of patient selection.

Local Recurrence and Survival Following Nerve Sparing Radical Cystoprostatectomy for Bladder Cancer: 10-Year Followup

PURPOSE The efficacy of nerve sparing radical cystoprostatectomy for the treatment of bladder cancer has been evaluated. We reviewed our 10-year experience with this technique to ascertain survival and local recurrence rates. MATERIALS AND METHODS The charts of 101 patients treated with nerve sparing cystoprostatectomy between March 1982 and November 1989 were reviewed and updated. RESULTS The disease-specific 10-year survival rate for all stages of bladder cancer treated was 69% and the 10-year survival rate free of local recurrence was 94%. Recovery of sexual function following nerve sparing cystectomy correlated with patient age: 62% in men 40 to 49 years old, 47% in men 50 to 59 years old, 43% in men 60 to 69 years old and 20% in men 70 to 79 years old. CONCLUSIONS Nerve sparing radical cystoprostatectomy does not compromise cancer control and provides improved postoperative quality of life.

Partial Nephrectomy: Technique Complications and Pathological Findings

PURPOSE We evaluate whether partial nephrectomy can be performed safely and efficaciously for renal tumors. MATERIALS AND METHODS The results of 67 partial nephrectomies performed between 1977 and 1994 for renal cell carcinoma (51), oncocytoma (9), angiomyolipoma (3), transitional cell carcinoma (3) and other nonneoplastic lesions (2) were analyzed retrospectively in detail. RESULTS Diminished complication rates were noted after 1988, and were attributed to improvements in surgical technique and an increased incidence of smaller, serendipitously discovered tumors. Although 35.5% of the patients had preoperative renal impairment (mean serum creatinine 2.1 mg./dl.), there were minimal changes in renal function and no patient required acute hemodialysis following partial nephrectomy. Among 42 patients with clinical stage T1 to T2 renal cell carcinoma undergoing partial nephrectomy local recurrence was identified in 8.3% of those with primary neoplasms. All 6 patients with local recurrence had negative surgical margins, recurrence often, distant from the operative site and multifocal disease, implicating multicentricity as the etiology of local recurrence. Five patients (83.3%) with local recurrence were alive and asymptomatic at a mean of 138 months after partial nephrectomy. Since capsular penetration was identified in 5 of 27 renal cell carcinomas (18.5%) with a diameter of 3.5 cm. or less, aggressive surgical resection with adequate tumor-free parenchymal and perinephric margins is necessary even for small lesions. CONCLUSIONS With improved surgical techniques, including regional hypothermia, intraoperative sonography, meticulous dissection and injection of the collecting system with methylene blue, partial nephrectomy is safe and effective in properly selected patients.

Quantitative pathologic changes in the human testis after vasectomy. A controlled study

To determine whether there are any deleterious changes in the human testis after vasectomy, we obtained testicular biopsy specimens from 31 healthy men undergoing vasectomy reversal and from 21 healthy, fertile volunteers. Morphometric analyses of these specimens revealed a 100 per cent increase in the thickness of the seminiferous tubular walls (P less than 0.001), a 50 per cent increase in the mean cross-sectional tubular area (P less than 0.001), and a significant reduction in the mean number of Sertoli cells (P less than 0.01) and spermatids (P less than 0.01) per tubular cross section in the post-vasectomy group, as compared with the control group. Focal interstitial fibrosis was observed in 23 per cent of the specimens from the post-vasectomy group and in none from the control group. There was a significant correlation (P less than 0.01) between interstitial fibrosis and infertility in patients who underwent a surgically successful vasectomy reversal (sperm in the ejaculate). None of the other measured characteristics correlated with infertility after vasectomy reversal. We conclude that significant morphologic changes occur in the human testis after vasectomy. The presence of focal interstitial fibrosis was associated with a high incidence of infertility in this series.

Surgical management of renal cell carcinoma with intracaval neoplastic extension above the hepatic veins.

Cardiopulmonary bypass, hypothermia, temporary cardiac arrest and exsanguination represent the next logical step in the evolutionary management of intracaval neoplastic extension with renal cell carcinoma. This method of management provides control of the circulation of the entire body and allows for careful dissection in a bloodless field with less risk of embolization. From 1981 to 1986, 15 patients were treated with intracaval neoplastic extension of renal cell carcinoma above the level of the most inferior hepatic veins. In 6 patients mobilization of the vena cava with division of the hepatic veins to the caudate lobe allowed excision of the tumor and tumor thrombus without cardiopulmonary bypass (group 1). The remaining 9 patients underwent cardiopulmonary bypass and hypothermia (group 2). There was 1 postoperative mortality in the entire group. Most patients had advanced regional disease but the feasibility of this technique has been demonstrated. Survival appeared to be less in the bypass group. Although some of the patients have had metastatic disease, the quality of life and survival have been prolonged in many of these acutely ill patients.

Molecular classification of renal tumors by gene expression profiling.

Renal tumor classification is important because histopathological subtypes are associated with distinct clinical behavior. However, diagnosis is difficult because tumor subtypes have overlapping microscopic characteristics. Therefore, ancillary methods are needed to optimize classification. We used oligonucleotide microarrays to analyze 31 adult renal tumors, including clear cell renal cell carcinoma (RCC), papillary RCC, chromophobe RCC, oncocytoma, and angiomyolipoma. Expression profiles correlated with histopathology; unsupervised algorithms clustered 30 of 31 tumors according to appropriate diagnostic subtypes while supervised analyses identified significant, subtype-specific expression markers. Clear cell RCC overexpressed proximal nephron, angiogenic, and immune response genes, chromophobe RCC oncocytoma overexpressed distal nephron and oxidative phosphorylation genes, papillary RCC overexpressed serine protease inhibitors, and extracellular matrix products, and angiomyolipoma overexpressed muscle developmental, lipid biosynthetic, melanocytic, and distinct angiogenic factors. Quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry of formalin-fixed renal tumors confirmed overexpression of proximal nephron markers (megalin/low-density lipoprotein-related protein 2, alpha-methylacyl CoA racemase) in clear cell and papillary RCC and distal nephron markers (beta-defensin 1, claudin 7) in chromophobe RCC/oncocytoma. In summary, renal tumor subtypes were classified by distinct gene expression profiles, illustrating tumor pathobiology and translating into novel molecular bioassays using fixed tissue.