Selective ablation of immature blood vessels in established human tumors follows vascular endothelial growth factor withdrawal.

Features that distinguish tumor vasculatures from normal blood vessels are sought to enable the destruction of preformed tumor vessels. We show that blood vessels in both a xenografted tumor and primary human tumors contain a sizable fraction of immature blood vessels that have not yet recruited periendothelial cells. These immature vessels are selectively obliterated as a consequence of vascular endothelial growth factor (VEGF) withdrawal. In a xenografted glioma, the selective vulnerability of immature vessels to VEGF loss was demonstrated by downregulating VEGF transgene expression using a tetracycline-regulated expression system. In human prostate cancer, the constitutive production of VEGF by the glandular epithelium was suppressed as a consequence of androgen-ablation therapy. VEGF loss led, in turn, to selective apoptosis of endothelial cells in vessels devoid of periendothelial cells. These results suggest that the unique dependence on VEGF of blood vessels lacking periendothelial cells can be exploited to reduce an existing tumor vasculature.

The expression of the imprinted H19 and IGF-2 genes in human bladder carcinoma.

The imprinted H19 gene is highly expressed in human embryos, fetal tissues and is nearly completely shut off in adults. However, it is reexpressed in a number of tumors including bladder carcinoma, demonstrating that H19 RNA is an oncofetal RNA. Tumors induced by injection of bladder carcinoma cell lines express H19 in contrast to the cells before injection. These observations support the notion of a positive correlation between H19 expression and bladder carcinoma. Loss of imprinting of H19 and IGF-2 was observed in samples of human bladder carcinoma.

Triorchidism--a reconstructive approach.

Testicular duplication is a relatively rare condition. A case is described in which conservative surgery was performed with reconstruction to produce a single testis.

Emphysematous renal and perirenal infection in nondiabetic patient.

Emphysematous renal infection is a severe, rare complication of urinary tract infection associated with gas production, which frequently causes renal destruction and has a high mortality rate. It is termed emphysematous pyelitis when gas is confined to the collecting system, or emphysematous pyelonephritis if it also involves the parenchyma with or without the perirenal space. Only 7 cases of perirenal emphysema have been described previously; all were in diabetics. Here we present a rare case of gas-producing renal infection in the collecting system and perirenal tissues, in a nondiabetic patient, and discuss the management of the various types of emphysematous renal infections.

Detection of bladder tumors by immunostaining of the Lewis X antigen in cells from voided urine.

OBJECTIVES: A study was made to determine the sensitivity and specificity of immunostaining of the Lewis X antigen in exfoliated urothelial cells from voided urine, for the detection and surveillance of bladder tumors. METHODS: Three consecutive voided urine specimens were obtained from 101 patients, 78 of whom were under surveillance because of a history of bladder tumors, and 23 were being evaluated because of hematuria or irritative urinary symptoms. Indirect immunoperoxidase staining of two urine samples was done on cytocentrifuge slides, using the P12 monoclonal antibody against the Lewis X antigen. The diagnosis of the presence of urothelial tumor was made if more than 5% of the cells showed a typical red-brown staining. Cytopathologic examination of the third urine specimen was done according to Papanicolaou. Each patient underwent cystoscopy, and biopsies were obtained whenever there was endoscopic evidence of bladder tumors or carcinoma in situ. RESULTS: Cystoscopy and biopsies revealed transitional cell carcinoma in 32 patients, whereas 69 patients had no evidence of bladder tumors. Immunocytology of one urine sample showed true-positive results in 26 of the 32 patients with bladder tumors, corresponding to a sensitivity of 81.25%. When two samples were examined, a sensitivity of 97% and a specificity of 85.5% were obtained. When the results of cytology and immunocytology were combined, sensitivity reached 100%. High-grade and low-grade transitional cell tumors were detected with equal efficiency. CONCLUSIONS: The use of P12 monoclonal antibody for evaluation of Lewis X reactivity in cytologic preparations from multiple voided urine specimens can improve the sensitivity of noninvasive detection of bladder cancer. The technique may ultimately replace cystoscopy in monitoring therapeutic response and tumor recurrence.

Percutaneous nephrostomy for assessment of functional recovery of obstructed kidneys.

The use of percutaneous nephrostomy to evaluate the recoverability of function of the obstructed kidney is described and examined as a practical clinical method. Long-term drainage was used to assess the functional status of four kidneys and found to be of great value. The use of percutaneous nephrostomy to evaluate function has been mentioned previously but has not become established. In view of inaccuracy of other methods of assessment, we consider percutaneous nephrostomy to be the most accurate predictive test available today and suggest criteria for its use.

Diagnosis and management of renal angiomyolipoma.

Renal angiomyolipoma (hamartoma) is an uncommon benign tumor of the kidney. Although about 400 cases of renal angiomyolipoma have been reported, it still causes difficulties in diagnosis and treatment. Until a few years ago it was almost impossible to arrive at a correct diagnosis preoperatively, and most of the cases underwent nephrectomy with the wrong diagnosis of renal carcinoma. More recently, abdominal computerized tomography and renal sonography have made it possible to reach the correct preoperative diagnosis in many cases, and thus to avoid unnecessary nephrectomies. We report on our experience with 13 cases of renal angiomyolipoma, and our conservative approach in a number of cases, which has enabled us to preserve renal tissue and function.

Place of extracorporeal shock-wave lithotripsy (ESWL) in management of cystine calculi.

We treated 12 patients with sixteen renal and one ureteral cystine stones primarily with extracorporeal shock-wave lithotripsy (ESWL). Among the stones thirteen were greater than 25 mm. In four stones less than 25 mm, three stones completely disappeared and 1 was reduced to small fragments, following ESWL. In thirteen stones greater than 25 mm, twelve were treated by ESWL initially, and one by surgery. Of the 12 cases treated initially by ESWL, 4 became stone-free, 4 remained with small fragments, and 1 remained with large fragments. Two patients were operated on because of poor response to ESWL and 1 patient lost kidney function because of prolonged obstruction. Disintegration of cystine stones greater than 25 mm required an average of 8,522 shock-waves in 4.33 sessions. The problems associated with application of ESWL monotherapy to cystine stones are presented.

Extracorporeal shock-wave lithotripsy (ESWL) monotherapy for stones in lower ureter.

Extracorporeal shock-wave lithotripsy (ESWL) has been accepted as the method of choice for most upper urinary tract calculi. However, in cases of stones in the lower ureter, ureteroscopic procedures have generally been preferred. Using the Dornier HM3 lithotriptor with modifications in the patient's position, we were able to successfully treat 155 unselected cases of lower ureteral calculi. The average stone size was 9.6 mm (range 5-23 mm). One hundred forty-three patients had stones located below the lower margin of the sacroiliac joint. These patients were placed in a supine position. The stones were visualized radiologically without use of a ureteral catheter in 78 percent of the patients; in 22 percent a ureteral catheter was inserted prior to ESWL to aid in stone localization. In 145 patients (94%) treatment was completed in one session; 10 patients (6%) required two sessions. Of the patients, 38 percent were free of stones one day after ESWL; 97 percent became stone free within three months, and only 3 patients required endoscopic manipulation, after ESWL. Twelve patients had stones in the midureter overlying the sacroileum. They were placed in the prone position, and the calculi were visualized with the aid of a ureteral catheter. All these patients became free of stones one month after treatment. There were no significant treatment-related complications except for bacteremia in 1 case. In view of the remarkable efficacy, negligible complication rate, and shorter hospital stay as compared to ureteroscopic stone manipulations, we recommend high energy ESWL as the primary monotherapy of mid and lower ureteral stones.

Colonic complications of ventriculoperitoneal shunts.

Late perforation of the large bowel by the abdominal catheter of a ventriculoperitoneal (VP) shunt is extremely rare. Four of the five reported patients subsequently died. We report here three patients who presented with this complication and were treated successfully. Bowel perforation by a VP shunt catheter should be considered when a shunt infection is secondary to gram-negative enteric organisms. It can occur without evidence of peritonitis, and the abdominal catheter can be removed percutaneously, thus avoiding a laparotomy.

Surgical aspects of gastrointestinal persimmon phytobezoar treatment.

One hundred thirteen patients presented with gastrointestinal complications due to persimmon phytobezoars during a 3 year period. One hundred three patients had a history of persimmon ingestion. One hundred five patients had undergone previous gastric operation for duodenal ulcer, one patient underwent highly selective vagotomy, and seven patients had not undergone previous operation. An elevated temperature, leukocytosis, and decreased bowel sounds were typical early clinical manifestations of small bowel obstruction by persimmon phytobezoars. In 13 patients, gastric bezoars were found, in 20 patients, gastric and intestinal bezoars, and in 80 patients, intestinal bezoars. One hundred patients were treated surgically. In 14 of the 20 patients with concomitant gastric and intestinal phytobezoars, extraction of the bezoars was achieved by gastrotomy. Of the remaining six patients, it was achieved by intraoperative milking of the gastric bezoar into the small bowel in two patients and by conservative treatment in four patients. Of the 100 patients who presented with small bowel obstruction, 60 were treated by milking of the bezoar into the large bowel, 34 by enterotomy, and 6 by conservative therapy with intravenous fluids, gastric suction, and a water-soluble contrast meal. Small bowel resection of a gangrenous segment was necessary in two patients. Two patients died after operation because of sepsis and respiratory complications. Eleven of the 13 patients in whom postoperative wound infection developed underwent gastrotomy or enterotomy. We conclude that the treatment of choice of intestinal obstruction due to persimmon phytobezoars is milking of the bezoar into the large bowel without enterotomy. Preoperative or operative endoscopy should be performed in patients presenting with complications of gastrointestinal phytobezoars. Patients who have undergone gastric operation should be warned against the risk of persimmon ingestion.

Static and flow cytometry.

It has been known for over 50 years that the amount of nuclear chromatin (DNA) in malignant neoplasms differs from that of homologous normal cells (1). More recently, it has been shown that nuclear DNA content correlates with the clinical outcome of various human neoplasms including urologic malignancies (2-10). An important problem in the care of patients with renal cell carcinoma (RCC) is the prediction of the neoplasms malignant potential, and in turn the patient's prognosis. Various parameters have been used to assess the malignant potential of renal cell carcinoma, including clinical and pathologic stage, histologic grade, tumor size, nuclear morphology, immunohistochemistry, age, elevated erythrocyte sedimentation rate, and hypercalcemia. To date, the most important predictors of prognosis in patients with RCC have been tumor pathologic stage, histologic grade and type (11,12). However, it has been shown that patients within a specified stage and grade may differ in their disease progression and survival (13,14). Furthermore, none of these variables alone or in combination has shown to provide total reliable prognostic information for the individual patient. These reasons led several groups to evaluate the prognostic value of nuclear DNA content in patients with renal cell carcinoma.

The clinical utility of transrectal ultrasound and digital rectal examination in the diagnosis of prostate cancer.

The development of high definition transrectal ultrasound probes has led to an increased interest in the ability of transrectal ultrasound of the prostate (TRUS) to assist in the diagnosis and management of prostate cancer. The present study was designed to examine the correlation of TRUS with digital rectal examination (DRE). The study group comprised 471 patients in whom the results of (a) DRE, (b) TRUS, and (c) histology of tissue obtained by transrectal biopsy of the prostate (TB), were all available. In those patients where both TRUS and DRE were negative, but prostate specific antigen (PSA) was greater than 10 micrograms ml-1, six random biopsies were performed. In all other cases the biopsies were TRUS directed to the suspicious lesion. There were 142 cases in whom both DRE and TRUS were negative or only mildly suspicious of malignancy. TB in these cases was positive for cancer in 17 cases (12%). In a further 126 cases, TRUS was positive for cancer, while DRE demonstrated no suspicious nodule. TB was positive in only 17 of these cases (13.5%). Similarly, in the 31 cases in which DRE was positive but TRUS was negative, TB was positive in only three cases (10%). In the 172 cases in whom both DRE and TRUS were positive, 99 biopsies were positive (57.5%). It was concluded from this study that DRE remains the most valuable single examination in the diagnosis of prostate cancer. TRUS increases the sensitivity of DRE if both are positive. When there is a discrepancy between the two examinations, the biopsy yield is low. When both are positive, a high cancer yield is obtained, TRUS having added value in directing the biopsy needle to the suspicious site. TRUS is thus a valuable adjunct to DRE in the diagnosis of prostate cancer.

Obstruction of urethral stents by mucosal overgrowth.

Urethral strictures are difficult to cure. In 1988, a new treatment was reported, consisting of dilation or incision of the stricture followed by implantation of a specially designed stent meant to allow the urethral epithelium to heal and cover the stent while preventing shrinkage of the scar and reappearance of the stricture. Two cases are reported here in which implantation of the stent resulted in a foreign-body reaction and obstruction of the lumen of the urethra. The area obstructed was reopened by transurethral removal of the reactive tissue. The long-term effect of this reaction on the patency of the urethra is still unknown.

Life-threatening retroperitoneal hematoma caused by anticoagulant therapy for myocardial infarction after SWL.

Extracorporeal shock wave lithotripsy, the primary treatment for renal and ureteral stones, is an elective procedure with a low rate of complications, although most patients have macrohematuria which lasts for a few hours, and as many as 25% develop a renal or perirenal hematoma. Therefore, SWL is not performed during anticoagulant therapy, and any blood dyscrasias should be corrected prior to the procedure. We present a case of a patient who had an acute myocardial infarction after SWL, was treated with anticoagulation and emergency coronary angioplasty, and subsequently developed a life-threatening retroperitoneal hemorrhage. Cessation of anticoagulation with fluid support and drainage of a pleural effusion eventually resulted in complete recovery.

Isolated pulmonary blast injury in rats--a new model using the extracorporeal shock-wave lithotriptor.

Blast injury to the lungs is one of the most overwhelming threats to survival following exposure to powerful explosions. The pathophysiology of blast injuries differs significantly from other forms of trauma. Using the extracorporeal shock-wave lithotriptor, originally designed for the noninvasive treatment of nephrolithiasis, we were able to produce isolated, typical pulmonary blast effects in rats. The immediate mortality was associated with bilateral pneumothorax and hemothorax. A nonlethal dose of shock waves caused intra-alveolar and intrabronchial hemorrhages and an immediate 2- to 3-fold increase in the lung weight. Additional marked increase in lung weight started 12 to 24 hours later, consistent with the clinical picture of delayed respiratory insufficiency which occurs after a latent period of 12 to 48 hours in many blast casualties. The use of air-containing vest as a protective measure completely prevented blast injury to the lungs.

[Treatment for cryptorchidism: at or after puberty?].

The patient with a cryptorchid testis is prone to infertility and testicular malignancy. Optimal treatment of cryptorchidism has been considered orchiopexy at the second year of life. In the past 10 years, we have treated 40 patients, 11-63 years old (mean 25), who presented with a cryptorchid testis at or after puberty. Orchiectomy was performed in all, and spermatogenesis was present in only 2 of the 40. Testicular diameter was greater than 3 cm in 32 of the 38 patients with an atrophic testis. Malignant tumors were found in 6 patients (15%) at operation. A seminoma was found in 5 patients operated on at ages 21, 23, 27, 47 and 63 years, and a nonseminomatous tumor in a 31-year-old. In 2 who underwent orchiopexy at ages 9 and 17 years, respectively, testicular tumors were found at ages 27 and 31 years. We conclude that a patient with a cryptorchid testis who presents at or after puberty should undergo orchiectomy as soon as possible. The prospect for such a testis to contribute to fertility is negligible, even if its diameter is normal, whereas the risk of developing malignancy is high.

[Congenital urethral strictures].

We present 12 patients with presumed congenital urethral stricture (mean age at diagnosis 20 years). They complained of various urological symptoms, including dysuria, transient urinary retention, urgency and reduced flow. The time from onset of symptoms to diagnosis averaged 18 months. The strictures were presumed congenital because no patient had a history of urethral infection or of instrumentation, and all the strictures were at the proximal bulbar urethra, as has been described for congenital, bulbar, urethral stricture. We treated 5 patients initially by internal urethrotomy, of whom 2 required transurethral dilatation at follow-up. 7 others were treated initially by transurethral dilatation, 4 of whom required more than 1 treatment. Follow-up has averaged 21 months. In 8 of 10 patients the maximal urinary flow at latest follow-up is greater than 20 ml/sec.

[Cystinuria and urolithiasis].

Cystinuria is a hereditary metabolic disorder which causes urinary lithiasis. Patients with cystinuria present at an earlier age (17 years), and with larger stones than patients with other types of urinary stones. As a result of frequent formation of new stones and multiple operations, many patients suffer from obstructive nephropathy and deterioration of kidney function. During the past decade we treated and followed 51 patients with cystine urolithiasis from 39 families. Screening disclosed another family member with cystinuria in 56% of the cases. The diagnosis of cystinuria was only made an average of 2 years after a patient first presented. In the group 12 kidneys had been removed due to various complications and in 7 kidneys there was significant deterioration of function. Each patient underwent a mean of 5.8 surgical interventions, including open operations, extra-corporeal shock wave lithotripsy (ESWL), percutaneous nephrolithotripsy (PCNL) and urethroscopy, but most still had residual stone fragments. To prevent complications from cystine urolithiasis every effort should be made to detect the disease early, including screening of families of patients with cystinuria and close follow-up of all family members. Early detection of stones, before they become large makes noninvasive treatment with ESWL possible, whereas large stones require PCNL. Patients should be urged to maintain high urine outputs and to continue uninterrupted treatment with penicillamine or tiopronin, and urinary alkalinization.

[Radical retropubic prostatectomy].

Radical prostatectomy may cure most patients in whom the malignant tumor has not invaded through the prostatic capsule. Advances in surgical technique and accumulation of experience have decreased the complication rate significantly. Long-term results of surgical treatment are now better than those of other forms of treatment; hence radical prostatectomy is now recommended for men with life expectancies longer than 10 years. Between 1988 and 1995, 164 men with clinical stages T1 or T2 adenocarcinoma were admitted for radical prostatectomy. Most were not offered a nerve-sparing procedure, so as to allow wider, more complete resection. Those who wanted preservation of sexual function underwent the nerve- preserving procedure. In 6 patients operation was discontinued when metastases to the mac lymph nodes were detected and in 1 when invasion of the pelvic wall was found, 157 underwent radical prostatectomy. Preoperative biopsy revealed a low-grade lesion (Gleason 2-4) in 19.1%, intermediate grade (Gleason 5-6) in 61.8% and high-grade (Gleason 7-9) in 19.1%; however, pathologic grading revealed that only 7.0% had grade 2-4 tumor, 60.5% grade 5-6 and 32.5% grade 7-9. Pathologic staging revealed T2 tumor in 58%, T3 in 38.8% (including microscopic invasion of the capsule or seminal vesicles); microscopic lymph node metastases were found in 3.2%. Tumor invasion through the capsule was found in only 2 of 13 treated with neoadjuvant androgen blockade, compared with 40% in those who did not receive this treatment. There was no operative mortality and only 14.7% has complications. All had urinary incontinence immediately after operation, but regained continence after an average of 4-5 months, 24 were incontinent for more than 12 months, but most of them had only mild stress incontinence. Most patients were impotent after the procedure. There was tumor recurrence, diagnosed by rise in serum PSA, in 26 during an average followup of 26.4 months (range 3-93). Cure rate of prostatic cancer by radical prostatectomy may be increased by improved preoperative staging methods and better patient selection; long term follow up is required for determining cure rate.