James A. Brown

Chromosomal Aneusomies Detected by Fluorescent in Situ Hybridization Analysis in Clinically Localized ProstateCarcinoma

Fluorescent in situ hybridization using 12 chromosome enumeration probes (for chromosomes 4, 6, 7, 8, 9, 10, 11, 12, 17, 18, X and Y) was used to evaluate fresh tumor touch preparations from 40 randomly selected radical prostatectomy specimens. Of the tumors 16 (40%) contained chromosomal aneusomies. Chromosome 8 was aneusomic in 9 tumors (23%). Gain of chromosome 7 was observed in 8 tumors (20%). Chromosome 17 was aneusomic in 4 cases, and chromosomes 10, 11, 12, 18 and Y were each aneusomic twice. Loss of chromosome 9 was observed in 1 tumor. Chromosomes 4, 6, and X were never aneusomic. The percentage of monosomy 17 nuclei was 2 to 4 times the amount noted with the other autosomes for tumor and benign tissue. Computer analysis demonstrated that these signals contained twice the signal density and were significantly different (p < 0.0001) than the single diploid chromosome 17 signals. This result is consistent with homologous pairing of chromosome 17 in benign and neoplastic prostate tissue. Anomalies of chromosomes 8 and/or 7 were present in 14 of the 16 cases (88%) aneusomic by fluorescent in situ hybridization. High grade tumors were more likely to be aneuploid on fluorescent in situ hybridization (p < 0.001). Tumors with chromosome 8 aneusomies were of higher stage (p < 0.05). Fluorescent in situ hybridization is more sensitive than flow cytometry for the detection of aneusomy/aneuploidy. The prognostic relevance of these findings will require further investigation.

Simultaneous Chromosome 7 and 17 Gain and Sex Chromosome Loss Provide Evidence that Renal Metanephric Adenoma is Related to Papillary Renal Cell Carcinoma

PURPOSE Metanephric adenoma has recently been recognized as a unique renal tumor characterized by an unusual degree of cellular differentiation and maturation. We recently studied metanephric adenoma using metaphase analysis and observed concomitant chromosome Y loss and chromosome 7 and 17 gain. To determine if these chromosomal anomalies are consistently present in renal metanephric adenoma, we studied all 11 tumors in the pathology tissue registry at our institution using fluorescence in situ hybridization (FISH). MATERIALS AND METHODS FISH, using deoxyribonucleic acid probes for chromosomes 1, 7, 8, 17, X and Y, was performed in isolated nuclei from 11 paraffin embedded renal metanephric adenoma specimens. RESULTS Of the 11 tumors (73%) 8 demonstrated chromosome 7 and 17 gain by FISH, and the remaining 3 were found to have an apparently normal chromosomal content. Of the 8 tumors (75%) from men showed 6 chromosome 7 and 17 gain with Y chromosome loss. Of the 3 tumors (33%) from women 1 had chromosome 7 and 17 gain with X chromosome loss, while 1 had chromosome 7 and 17 gain without sex chromosome aneusomy. Metaphase analysis performed on 2 tumors revealed chromosome 7 and 17 gain and Y chromosome loss in 1, and no apparent, chromosome anomaly in the other, confirming the results of FISH analysis. CONCLUSIONS FISH analysis of renal metanephric adenoma identified frequent chromosome 7 and 17 gain and sex chromosome loss. These results are consistent with a clonal neoplastic disorder in which chromosomes 7, 17, X and Y are likely to be involved in the pathogenesis of this tumor. These characteristic chromosomal alterations have also been observed in papillary renal cell adenoma and papillary renal cell carcinoma, providing evidence that these tumors may be related.

Laparoscopic Marsupialization of Symptomatic Polycystic Kidney Disease

PURPOSE Although laparoscopic unroofing of simple renal cysts has proved to be an effective form of therapy, its use for treatment of multiple renal cysts or symptomatic autosomal dominant polycystic kidney disease only recently has been investigated. MATERIALS AND METHODS The results of laparoscopic marsupialization of symptomatic renal cysts in 13 patients was determined 12 to 28 months postoperatively by assessing subjective pain relief, and comparing preoperative and postoperative computerized tomography (CT). Eight patients had autosomal dominant polycystic kidney disease. Multiple dominant (more than 3 cm.) cysts were marsupialized in 11 patients and 1 dominant cyst was treated in 2. RESULTS Of 13 patients with symptomatic renal cysts and 8 with autosomal dominant polycystic kidney disease 8 (62%) and 4, respectively, were pain-free 12 to 28 months postoperatively. Two patients had persistent pain, while 3 had recurrent pain 7 to 16 months postoperatively. All 5 patients had persistent or recurrent dominant cysts on followup CT. Followup CT demonstrated resolution or a significant decrease of the largest and all or all but 1 of the other dominant cysts in 6 of 7 pain-free patients. Intraoperative ultrasound detected unidentified cysts during an open and laparoscopic procedure. No deleterious effects on serum creatinine were observed. CONCLUSIONS Laparoscopic marsupialization is a safe, relatively successful technique for providing persistent pain relief in patients with autosomal dominant polycystic kidney disease. Although the 2-year pain-free rate approaches the 62% rate reported for open surgical cyst resection, continued efforts to improve current laparoscopic techniques are clearly indicated. Persistence or recurrence of dominant cysts on CT correlated with persistent or recurrent symptoms. Intraoperative ultrasound is effective in identifying dominant cysts.

Fluorescence In Situ Hybridization Analysis of Renal Oncocytoma Reveals Frequent Loss of Chromosomes Y and 1

PURPOSE Cytogenetic studies of a small number of renal oncocytomas have indicated that loss of chromosomes 1 and Y may be involved in the pathogenesis of this tumor. To evaluate these observations further we selected paraffin embedded renal oncocytoma specimens from 20 male and 10 female patients for fluorescence in situ hybridization analysis. MATERIALS AND METHODS Isolated nuclei were prepared from paraffin embedded specimens, and fluorescence in situ hybridization was performed with enumeration probes for chromosomes 1, 12, X and Y. RESULTS Tumors from 10 male (50%) and 4 female (40%) patients demonstrated chromosomal alterations. Loss of chromosome Y was observed in specimens from all 10 male patients, and loss of chromosome 1 or gain of chromosome 12 was noted in 5 and 2 of these specimens, respectively. Of the 4 female patients with chromosomal abnormalities 2 had loss of chromosome 1, 1 had gain of chromosome 1 and 1 had gain of chromosome 12. CONCLUSIONS Our results confirm that loss of chromosomes Y and 1 is common in renal oncocytoma, and that the alterations are probably involved in the pathogenesis of this tumor.

Metaphase analysis of metanephric adenoma reveals chromosome Y loss with chromosome 7 and 17 gain

A 61-year-old man underwent wedge excision of a 3-cm right renal metanephric adenoma. This recently recognized tumor has been considered benign, although no genetic studies have been reported. Metaphase analysis demonstrated a 47,X,-Y,+7,+17 karyotype. These results are consistent with a clonal neoplastic disorder.

Fluorescence in situ hybridization aneuploidy as a predictor of clinical disease recurrence and prostate-specific antigen level 3 years after radical prostatectomy.

OBJECTIVE To determine if fluorescence in situ hybridization (FISH) analysis of fresh-tissue biopsy specimens obtained at the time of radical prostatectomy is able to predict prospectively clinical disease progression or prostate-specific antigen (PSA) level in patients 3 to 4 years after surgery. MATERIALS AND METHODS FISH analysis was performed on fresh-tissue touch preparations obtained from 90 randomly selected radical prostatectomy specimens. Cut surface touch preparations from 40 specimens resected in 1992 were analyzed with DNA probes for chromosomes 4, 6-12, 17, 18, X, and Y. Needle-biopsy specimens were obtained from 50 tumors resected in 1993, and touch preparations from these specimens were studied with DNA probes for chromosomes 7, 8, 11, and 12. Serum PSA levels and clinicopathologic data were recorded, and each patient was followed up from the time of surgery to determine cancer progression. RESULTS Of 90 patients undergoing radical prostatectomy in 1992 and 1993, 89 returned for follow-up. Three patients received preoperative hormonal therapy, and in 2 patients, antiandrogen therapy was continued postoperatively. Fifteen patients underwent intraoperative orchiectomy immediately after radical prostatectomy, while 9 patients had postoperative adjuvant hormonal therapy. Six patients underwent postoperative radiation therapy. Fourteen patients (15.7%) demonstrated systemic, local, or PSA progression. Only 2 (4.7%) of 43 patients with FISH diploid tumors demonstrated cancer progression. Conversely, 10 (30.3%) of 33 FISH aneuploid and 12 (26.1%) of 46 FISH nondiploid tumors demonstrated cancer progression (P=.004 and P=.006, respectively). Unlike FISH, flow cytometric aneuploidy was not associated with early cancer progression. Elevated preoperative PSA concentration, increased preoperative and postoperative Gleason score, and increased preoperative and postoperative T or N stage were not statistically significantly associated with cancer progression. While chromosome 7 and 8 aneusomies were not statistically associated with cancer progression, 2 of 5 (P=.04) chromosome 12 aneusomic tumors demonstrated cancer progression. CONCLUSION Early (within 4 years) local, systemic, or PSA progression occurred more frequently (P<.05) in radical prostatectomy patients with FISH aneuploid, nondiploid, and chromosome 12 aneusomic tumors. Flow cytometric ploidy status, preoperative serum PSA concentration, and clinical or pathologic grade or stage, including seminal vesicle involvement, margin status, and capsular perforation status, were not associated with early prostate cancer progression in this group of 89 patients. FISH analysis appears to be a useful preoperative tool for predicting aggressive vs indolent prostate cancer.

Erythropoietin-induced recurrent veno-occlusive priapism associated with end-stage renal disease

This is the first report of a male hemodialysis patient experiencing recurrent dialysis-associated priapism that resolved when his concurrent erythropoietin dose was reduced from 2000 to 1500 U one time per week and held if his hemoglobin was greater than 10 g/dL. We discuss dialysis-associated priapism and the effects of erythropoietin on the coagulation cascade and male hormone levels in an effort to elucidate the etiology of priapism in this patient.

Genitourinary neurofibromatosis mimicking posterior urethral valves.

A 12-year-old boy, examined after an episode of acute urinary retention, was found to have neurofibromatosis of the bladder neck and prostatic urethra. His symptoms of bladder outlet obstruction and radiographic findings of a dilated prostatic urethra mimicked posterior urethral valves. Complete urologic investigation, including cystourethroscopy, revealed that the dilatation of the prostatic urethra was secondary to neural involvement of the external sphincter and posterior urethra without mechanical obstruction or posterior urethral valves.

A symptomatic testicular cyst in a patient with von hippel-lindau disease

Von Hippel-Lindau disease (VHL) is an autosomal-dominant condition that often involves cystic changes within many organs, including the epididymis. However, no previous report of a patient with VHL and a benign intratesticular cyst has been published. We report on a 28-year-old man with otherwise stable VHL who presented with a symptomatic 3-cm intratesticular benign cyst. The cyst was successfully treated by partial orchiectomy.

Use of a surgical sponge facilitates rib resection in flank incisions.

Dissection of the rib in a flank incision is often tedious and difficult. Entry into the pleural space and subcostal nerve injury are two frequent complications. In an effort to reduce the frequency of these complications and to facilitate the ease of rib dissection and resection, we describe a technique that uses a moistened surgical sponge to dissect free the posterior surface of the rib.