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A 71-year-old male with history of clear cell renal cell carcinoma (RCC) 6-years status post nephrectomy presented for gross hematuria. Cystoscopy revealed a bulge of the right ureteral orifice, and transurethral resection confirmed RCC metastasis to the ureteral stump. Ureterectomy with bladder cuff excision was performed, and the patient is currently undergoing aggressive imaging surveillance. This is the 57th case of metastasis of RCC to the ureteric stump, and this case occurred beyond baseline surveillance recommendation of five years. Potential mechanisms of metastasis of RCC are reviewed, and RCC surveillance is discussed.

A 61-year-old male presented with gross hematuria and transurethral resection of bladder tumor revealed inflammatory myofibroblastic tumor (IMT). Due to extent of disease leading to ureteral obstruction and hydronephrosis, radical cystectomy (RC) with ileal conduit urinary diversion was performed. Five months after RC, the patient presented with decreased urine output. Exploratory laparotomy revealed mass in right colon and right hemicolectomy revealed metastatic IMT to the bowel and pericolonic fat. To our knowledge, this is the first report of primary IMT of the bladder metastasizing to other organs. Keywords: Inflammatory myofibroblastic tumor, Inflammatory pseudotumor, Bladder tumor, Urinary bladder, Spindle cell tumor

Introduction After a failed transplant, management of a non-functional graft with pain or recurrent infections can be challenging. Transplant nephrectomy (TN) can be a morbid procedure with the potential for significant blood loss. Embolization of the renal artery alone has been proposed as a method of reducing complications from an in vivo failed kidney transplant. While this does yield less morbidity, it may not address an infected graft or refractory hematuria or rejection. We elected to begin preoperative embolization to assess if this would help decrease the blood loss and transfusion rate associated with TN. Materials and Methods We performed a retrospective analysis of all patients who underwent non-emergent TN at our institution. Patients who had functioning grafts that later failed were included in analysis. TN was performed for recurrent infections, pain or hematuria. We evaluated for blood loss (EBL) during TN, transfusion rate and length of hospital stay. Results A total of 16 patients were identified. Nine had preoperative embolization or no blood flow to the graft prior to TN. The remaining 7 did not have preoperative embolization. The shortest time from transplant to TN was 8 months and the longest 18 years with an average of 6.3 years. Average EBL for the embolized patients (ETN) was 143.9cc compared to 621.4cc in the non-embolized (NETN) group (p=0.041). Average number of units of blood transfused was 0.44 in the ETN with only 3/9 patients requiring transfusion. The NETN patients had average of 1.29 units transfused with 5/7 requiring transfusion. The length of stay was longer for the ETN (5.4 days) compared to 3.9 in the NETN. No intraoperative complications were seen in either group and only one patient had a postoperative ileus in the NETN. Conclusion Embolization prior to TN significantly decreases the EBL but does not significantly decrease transfusion rate. However, patients do require a significantly longer hospitalization with embolization due to the time needed for embolization. Larger studies are needed to determine if embolization before transplant nephrectomy reduces the transfusion rates and overall complications.

Riley J, Troxel S, Wakefield M, Ross G, Weinstein S. Laparoscopic donor nephrectomy – safety in a small-volume transplant center. Clin Transplant 2010: 24: 429–432. © 2009 John Wiley & Sons A/S. Abstract: Introduction: Laparoscopy is a standard surgical option for live donor nephrectomy (LDN) at the majority of transplant centers. Equivalent graft survival with shorter convalescence has been reported by several large volume centers. With the arrival of an experienced laparoscopic surgeon in 2002, we began to offer laparoscopic LDN at our institution. We report our experience as a large volume laparoscopic surgery program but a low volume transplant center. Methods: A retrospective review of the previous 34 LDN (17 open, 17 laparoscopic) performed at the University of Missouri were included. A single laparoscopic surgeon performed all laparoscopic procedures. Hand assisted laparoscopy was performed in 15 and standard laparoscopy with a pfannenstiel incision in two. Open procedures were performed through anterior subcostal or flank incision. A single surgeon performed all open procedures. Results: There was no statistical difference in age, body mass index or American Society of Anesthesiologies Score between the two groups. Mean operative time, estimated blood loss and hospital stay were 229 minutes, 324 cc and 2.2 days respectively in the laparoscopic group compared to 202 minutes, 440 cc and five days for the open group. Average warm ischemia time was 179 seconds. Recipient creatinine for the two groups at one week, one month and one year was not statistically significantly different. Each group had one graft loss due to medication noncompliance. Conclusion: For small transplant centers with an advanced laparoscopic program, laparoscopic LDN is a safe procedure with comparable outcomes to major transplant centers.

Objectives To determine if toxic serum levels of neomycin are generated after direct corpora cavernosa irrigation during penile prosthesis placement. Methods We have used an infection prophylaxis technique that involves directly irrigating the corpora cavernosa tissue (through the corporotomy) with 0.5% neomycin solution. Serum neomycin concentrations were measured at 1 hour and 4 hours after irrigation in 13 patients undergoing penile prosthesis placement. A subset of patients who had preimplant and postimplant serum creatinine concentrations was evaluated for changes in renal function. Results The mean 1-hour postirrigation serum neomycin level was 1.2 μg/mL and the mean 4-hour postirrigation level was 1.2 μg/mL. These serum neomycin concentrations are lower than those thought to be necessary to produce nephrotoxicity or ototoxicity. Renal function was not significantly affected by the neomycin irrigation. Conclusions Although aminoglycosides are ototoxic and neomycin has the highest nephrotoxic potential of the aminoglycosides, we conclude that direct irrigation of the corpora cavernosa with 0.5% neomycin solution does not produce significant systemic exposure to result in nephrotoxicity or ototoxicity. One-time prophylactic neomycin irrigation remains an effective, safe, and economic adjunct to penile prosthesis placement.

The relative contribution of the gut, liver, and lungs as sites of first-pass bioactivation (hydrolysis) of the orally administered ester prodrug, zofenopril calcium (SQ 26,991), to the active angiotensin converting enzyme (ACE) inhibitor, SQ 26,333, was determined. With a five-way study design, two dogs each received a single 1.6-mg/kg dose of zofenopril [as its soluble potassium salt (SQ 26,900)] via the following routes of administration: intraarterial, intravenous, intraportal, and oral. Each dog also received an equimolar oral dose of zofenopril calcium (1.5 mg/kg). Concentrations of zofenopril in plasma were quantitated with a GC/MSD assay. Extraction ratios (E) for zofenopril by the gut, liver, and lungs were calculated based on the ratios of the area under the curve (AUC) values of zofenopril in arterial plasma after administration by the various routes. As individual eliminating organs, the gut and liver each had a high intrinsic capability to hydrolyze zofenopril; E values ranged from 45 to 89%. The lungs were found to have low, but measurable, hydrolytic activity with estimated E values that ranged from 5 to 26%. Overall, about 95% of the orally administered dose of zofenopril calcium was hydrolyzed during the first pass. Because the prodrug is sequentially exposed to the gut, liver, and lungs, the contribution of the gut to the overall first-pass hydrolysis (ca. 87%) was estimated to be significantly greater than that of the liver (

A total of 96 patients were treated for localized carcinoma of the prostate using combined Iodine-125 (125I) implantation and external beam radiotherapy. The implant was tailored to deliver 10,000 rad to the periphery of the prostate. A significant incidence of serious late rectal complications was observed. Positive pelvic nodes were found in 28 percent of the patients. Disease-free survival at seven years was 76 percent for those with negative nodes and 46 percent for patients with positive nodes.

Multicystic dysplastic kidney is a common renal anomaly in the newborn. Long-term problems, such as pain, infection, hypertension and neoplasm, although infrequent, have been reported. Acute, life-threatening complications resulting from the size of the affected kidney are rare and emergency nephrectomy has been the only reported effective therapy. We present a case of ultrasound-guided percutaneous cyst decompression used as definitive treatment of respiratory failure associated with multicystic dysplastic kidney.

Sixty-three patients with cancer of the prostate T2 or T3 were evaluated. The protocol of treatment called for pelvic lymphadenectomy, 10,000 rad from I125 implant and 4000 rad in 20 fractions using a Cobalt60 machine. They were followed for 1 to 5 years with a plan to rebiopsy the prostate 1 to 2 years after therapy. Six of 59 evaluable patients (10%) showed progressive disease. Distinctive prognostic features in the failure group were younger age, larger prostate, more advanced stage, poorer differentiation, more possibility of positive pelvic lymph nodes, and if the nodes were positive, the involvement of more than two pelvic lymph nodes. On the other hand, the patients with controlled disease with or without positive prostatic biopsy on follow-up showed identical features regarding age, size of prostate, stage, differentiation, involvement of pelvic lymph nodes, and if the nodes were positive, only one or two nodes involved. Positive biopsy 1 to 2 years after radical irradiation in otherwise controlled disease is considered of no prognostic value.

SUMMARY Errors in clinical staging of bladder carcinoma occur in about 50 per cent of patients. Sources of error include (1) a variable assortment of diagnostic studies performed, (2) inexactitudes inherent in the diagnostic measures employed, (3) insufficient corroboration by surgical and pathologic staging, (4) the lack of a satisfactory means for detecting micrometastases, and (5) a generalized confusion regarding the multiple classifications available for clinical staging. More precise clinical staging will be influential in treatment decision-making and in prognosis. Minimum requirements for clinical staging of the primary tumor currently include complete examination, excretory urography, cystoscopy, bimanual examination under anesthesia, and transurethral resection or biopsy. Polycystography, triple contrast cystography and arteriography may be helpful occasionally to document muscle invasion. Pedal lymphangiography and lymphography can in selected cases be helpful in detecting otherwise silent nodal involvement in spite of its inability to demonstrate many primary or regional lymph nodes. Familiarity with the above diagnostic options and the advantages and limitations of each is essential for each physician caring for a patient with bladder carcinoma. Conversion to TNM classification for bladder carcinoma that is similar to that of the UICC seems appropriate (1) because of its more rational approach to extent of involvement by primary tumor, lymph node and distant sites, and (2) in order for our western hemisphere urologists to communicate better with our colleagues from around the globe. Such a system is now under consideration by a subcommittee of the American Joint Committee on Staging and End Result Reporting.

During the past year 25 patients with advanced transitional cell carcinoma were treated with intravenous doxorubicin hydrochloride (Adriamycin), 60 to 75 mg. per square meter of body surface area, every three weeks. Among the 19 evaluable patients, one partial objective remission lasting five months was observed. All 7 patients with bone pain had symptomatic relief and 12 patients had significant subjective improvement lasting an average of six-and-a-half months. Side effects were minimal and consisted of alopecia, mild leukopenia, and mild stomatitis; no significant cardiotoxicity was observed. Doxorubicin hydrochloride appears to have important antitumor activity in advanced urothelial tumors. Controlled clinical trials with this agent alone and in combined drug regimens are needed.

Sixty-three consecutive patients with cancer of the prostate treated by pelvic lymphadenectomy, I-125 implantation +/- Co60 therapy were studied regarding the impact of extension of cancer beyond the capsule and minimal nodal involvement. Extension of cancer beyond the prostatic capsule, Stage T3, constituted 34%, while Stages T0-2 comprised 66% of the cases. The features of T3 compared with T2 or less were: higher incidence of younger age (50s), 29% vs. 19%; less well-differentiated cancer, 29% vs. 64%; higher incidence of pelvic node involvement, 52% vs. 18%; and higher incidence of recurrence, 24% vs. 4.7%. The involvement of only one or two pelvic nodes by microscopic cancer did not adversely affect the prognosis in T2 group over a relatively short period of follow-up. No local recurrence occurred in T2. In the T3 group, two of 21 (9.5%) developed local recurrence.

The development of a liquid scintillator solvent that can hold up to 4.5 ml of H2O per 10 ml of solvent is described. This solvent consists of 1% butyl-PBD and 6% naphthalene in dioxane. A nitric acid digestion system for use in conjunction with this solvent is applicable to a wide range of animal tissues, is relatively rapid, calls for minimum modification from tissue to tissue, and generally yields colorless counting solutions without need for special decolorization techniques. It must be emphasized that this system was designed for ambient temperature operation and is unusable in refrigerated spectrometers.

Twenty-five patients with advanced transitional cell carcinoma of the urinary tract were treated with doxorubicin hydrochloride (Adriamycin). Eight evaluable patients who received extensive external irradiation therapy and at least two doses of doxorubicin hydrochloride were studied to assess bone marrow toxicity and possible augmentation of radiation dermatitis. Myelosuppression was similar in both irradiated patients and those who received doxorubicin alone. None of the irradiated patients displayed skin augmentation reactions with doxorubicin. In the dose range used chemotherapy with doxorubicin did not appear to be particularly hazardous in irradiated patients.

A prospective analysis was done on 318 patients with bladder cancer observed during a 4-year period. We examined the predictive value for tumor recurrence of the initial grade, stage, number and size of bladder tumors. None of the observed parameters alone or in combination could predict tumor recurrence. Cystoscopy and cytology, as well as random bladder and tumor biopsies, were part of the diagnostic studies.

Fifty-seven patients with localized carcinoma of the prostate were treated with pelvic lymphadenectomy and a reduced 125iodine implant dosage, supplemented by a moderate dose of external beam radiotherapy to the whole pelvis delivered 4 to 6 weeks later. The incidence of pelvic nodal metastases was 28 per cent and the operative morbidity was 15 per cent. Late radiation sequelae developed in 18 patients, including 15 patients with radiation proctitis (29 per cent), among whom 2 (4.6 per cent) suffered rectal ulceration and required diverting colostomy. Followup has been 2 years or longer (median 33 months) in 26 patients, of whom 22 (85 per cent) are free of disease. Three patients are living with osseous metastases or local disease and there has been 1 death of prostatic carcinoma, for an absolute 2-year survival rate of 95 per cent. Of the 7 patients with poorly differentiated tumor and of the 8 patients with positive pelvic lymph nodes 5 and 6, respectively, remain free of disease after a minimum 2-year followup. Potency has been lost in 20 per cent and reduced significantly in 30 per cent of the patients followed 18 months or longer. Prostatic biopsies on 28 asymptomatic patients 12 to 30 months after completion of therapy showed no tumor in 21 (75 per cent).

We present a case study of a patient with seminoma who had normal testicles on palpation. Testicular ultrasound is the technique of choice to locate occult nonpalpable testis lesions. We recommend its use in the search for the source of any retroperitoneal mass of undetermined origin.

The University of Missouri-Columbia protocol for localised cancer of the prostate calls for pelvic node dissection, 10 000 cGy at the periphery of the prostate from 125 I and 4000 cGy in 20 fractions to the whole pelvis using supervoltage X-ray therapy. Rectal complications were studied in 104 patients; acute and chronic reactions were defined. During external irradiation 54% did not develop diarrhoea, 43% had mild diarrhoea and 3% had severe diarrhoea. In the chronic stage 77% did not have diarrhoea, 12% had delayed, non-distressing rectal bleeding which did not need specific treatment or needed only simple treatment, 7% had prolonged distressing proctitis and 4% had rectal ulceration or recto-urethral fistula necessitating colostomy. Each of the four patients who had colostomy had an additional aetiological factor (arterial disease, pelvic inflammation, additional radiation, pelvic malignancy or second operation). None of the patients entered in the combined brachytherapy and teletherapy programme, and in whom 0.5 cm space was maintained between the closest seed and the rectal mucosa, developed prolonged proctitis.

Intravenous drug abuse may produce end stage renal disease. In a small group of formerly addicted Federal prisoners on dialysis cadaveric renal transplantation has provided an effective alternative to chronic dialysis. This finding may relate to some abrogation of the immune system in such patients.

A sensitive, specific high-performance liquid chromatographic procedure was developed for the determination of plasma ethmozin levels. Basic plasma samples were partitioned with methylene chloride. The organic extract was washed with water and then evaporated to dryness under reduced pressure. The residue was redissolved in 0.2 ml of the mobile phase, consisting of hexane-tetrahydrofuran-methanol-water (66:27:6,30:0.7 v/v), and then chromatographed on a microporous silica column. With a variable-wavelength UV detector set at 268 nm, 10 ng of ethmozin/ml of plasma was measured. The utility of the method for human pharmacokinetic studies was demonstrated.

In an evaluation of the use of topical triethylenethiophosphoramide for therapy and prevention of recurrent multiple superficial transitional cell carcinoma of the bladder retrograde cystography was done. Unilateral or bilateral vesicoureteral reflux was demonstrated in 9 consecutive patients studied. Retrospective analysis uncovered 9 additional patients with bladder cancer and reflux. The discovery of vesicoureteral reflux prompts currently unanswerable questions regarding the etiology and pathogenesis of urothelial malignancy, as well as the role of topical chemotherapy in superficial tumors.

A rapid, sensitive assay for angiotensin-converting enzyme (ACE) inhibitors is described. Biological samples were diluted with methanol to precipitate endogenous ACE and centrifuged. Supernatants were further diluted with 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid buffer, pH 8. Diluted samples were incubated at 37 degrees C with the substrate [3H]hippurylglycylglycine and rabbit lung ACE for 45 min. Acid (1.0 N HCl) was then added, and the product, [3H]hippuric acid, was extracted into a water-immiscible scintillation cocktail. Drug standards were prepared in the biological matrix to correct for drug recovery. A computer program was used to convert radioactivity (dpm) to units of enzyme activity and then correlate enzyme activity with drug concentration. The ester prodrugs fosenopril and enalapril could be assayed down to 4 ng/ml in plasma after ester hydrolysis with NaOH. Drug disposition studies in rats, dogs, and monkeys have demonstrated that the method can be readily adapted to any ACE inhibitor and is suitable for determining drug bioavailability and pharmacokinetics.

Serum concentrations of Immunoglobulins G, A and M (IgG, IgA and IgM) were measured by immunodiffusion In a control population of 58 patients and In 165 patients with cancer of the pros-state, bladder, kidney or testis. Tumor patients were ranked according to clinical staging. In a smaller group of patients serum levels of IgE were measured by radioimmunoassay. IgG, IgA and IgM concentrations did not correlate with staging or the presence of malignancy. However, a statistically significant correlation between increased IgE levels and advanced bladder cancer (stages D1 and D2) stimulated us to study more patients with bladder tumors. In a subsequentgroup of 22 bladder tumor patients this trend could not be reproduced. IgE levels did not correlate with a history of allergy in any of the patients tested. Concentrations of immunoglobulins G, A, M and E seem to be unchanged in genitourinary malignancies, although their functional role here has not been assessed qualitatively.

Naloxone, 7,8-dihydro-14-hydroxynormorphinone, and N-allyl-7,8-dihydro-14-hydroxynormorphine have been idenfied in a human urine specimen after naloxone administration. The metabolites were isolated, after hydrolysis with glusulase, by column chromatography and identified by TLC and spectrofluorimetry. These findings indicate that both N-dealkylation and the reduction of the 6-keto group of naloxone as well as glucuronide formation occur in man. Evidence is also presented indicating that N-allyl-7,8-dihydro-14-hydroxynormorphine formation occurs in rabbits as well as in man and the chicken.

The effect of route of administration on the absorption and distribution of naloxone, a narcotic antagonist, was investigated in rats. Plasma levels were determined by GLC. Five minutes after intravenous administration of 1 mg./kg., the plasma concentration was 258 ng./ml. Plasma levels after low oral doses were undetectable; but after 100 mg./kg. orally, the peak level of unchanged drug was almost 5000 ng./ml. In terms of percent of administered dose, the maximum amount of naloxone in the calculated plasma volume is 1.04% of the intravenous dose versus 0.19% of the oral dose. Pharmacokinetic parameters were generated with a computer program; the models constructed are of a rapidly absorbed and rapidly excreted and/or metabolized drug. These results, together with results from absorption studies with ligated intestinal loops, indicate that poor absorption of naloxone is not the cause of its relatively low oral potency. In vitro metabolic studies with rat liver slices confirmed rapid naloxone metabolism, suggesting that the lower potency of oral naloxone compared to parenteral naloxone is due to rapid first-pass liver metabolism.

An electron-capture GLC method is described for oxycodone and its major metabolite, noroxycodone, in plasma and urine. The method involves extraction of the two substances into benzene-isopropranol at pH 10.4, followed by back-extraction into 0.1 N HCl. The acid phase is washed with hexane and made alkaline prior to reextraction into benzene-isopropanol. The solvent is removed by evaporation, and the heptafluorobutyryl derivatives of the test substances are formed. After removal of excess reagent, oxycodone and noroxycodone are quantitated by GLC. The characteristics of both substances, with respect to plasma levels in dogs and analgesic activity in mice, are reported. Isolation of noroxycodone from human urine and its identification by TLC, GLC, and mass spectrometry are described.