Bernard M. Churchill

The Results of Radical Nephrectomy for Renal Cell Carcinoma

SummaryA series of 88 cases of renal cell carcinoma treated by radical nephrectomy is presented showing a statistically significant improvement in the 3,5 and 10-year survival rates. This increased survival rate is due to 3 factors: 1) early ligation of the renal artery and vein, 2) complete removal of the perinephric envelope and 3) surgical extirpation of the lymphatic field. Prognosis is directly related to the stage and grade of the tumor. Some ancillary aids in the preoperative prognostic evaluation of the tumor are suggested and discussed.

Use of Electrochemical DNA Biosensors for Rapid Molecular Identification of Uropathogens in Clinical Urine Specimens

ABSTRACT We describe the first species-specific detection of bacterial pathogens in human clinical fluid samples using a microfabricated electrochemical sensor array. Each of the 16 sensors in the array consisted of three single-layer gold electrodes—working, reference, and auxiliary. Each of the working electrodes contained one representative from a library of capture probes, each specific for a clinically relevant bacterial urinary pathogen. The library included probes for Escherichia coli, Proteus mirabilis, Pseudomonas aeruginosa, Enterocococcus spp., and the Klebsiella-Enterobacter group. A bacterial 16S rRNA target derived from single-step bacterial lysis was hybridized both to the biotin-modified capture probe on the sensor surface and to a second, fluorescein-modified detector probe. Detection of the target-probe hybrids was achieved through binding of a horseradish peroxidase (HRP)-conjugated anti-fluorescein antibody to the detector probe. Amperometric measurement of the catalyzed HRP reaction was obtained at a fixed potential of −200 mV between the working and reference electrodes. Species-specific detection of as few as 2,600 uropathogenic bacteria in culture, inoculated urine, and clinical urine samples was achieved within 45 min from the beginning of sample processing. In a feasibility study of this amperometric detection system using blinded clinical urine specimens, the sensor array had 100% sensitivity for direct detection of gram-negative bacteria without nucleic acid purification or amplification. Identification was demonstrated for 98% of gram-negative bacteria for which species-specific probes were available. When combined with a microfluidics-based sample preparation module, the integrated system could serve as a point-of-care device for rapid diagnosis of urinary tract infections.

Ureteral Bladder Augmentation

Virtually all segments of the gastrointestinal tract have been used successfully in augmentation cystoplasty. The complications inherent in enterocystoplasty are well described. Megaureters subtending effete kidneys (poorly or nonfunctioning) provide a novel and excellent source of augmentation material with urothelium and muscular backing, free of the electrolyte and acid base disturbances, and mucus production that plague enterocystoplasty. Augmentation cystoplasty using detubularized, reconfigured, otherwise disposable megaureter, with or without ipsilateral total or partial nephrectomy, was performed in 16 patients (mean age 8.8 years, range 1 to 25) with inadequate and dysfunctional bladders. Postoperative followup varied between 8 and 38 months (mean 22). The overall renal function and radiographic appearance of the remaining upper tracts have remained stable or improved in all patients. Of the 16 patients 15 require intermittent catheterization and 1 voids spontaneously. Ten patients are continent day and night, 5 have improved continence (4 damp at night and 1 stress incontinence) and 1 has failed to gain continence despite good capacity and compliance. Complete postoperative urodynamic evaluations in 12 of 13 patients show good capacity, low pressure bladders with no instability. Complications occurred in 5 patients, including transient urine extravasation in 2, contralateral ureterovesical obstruction in 2 and Mitrofanoff stomal stenosis in 1. Augmentation ureterocystoplasty combines the benefits common to all enterocystoplasties without adding any of the untoward complications or risks associated with nonurothelial augmentations.

Acquired Renal Scars in Children

To determine the important factors involved in the etiology of renal scarring we studied 37 children with renal scars seen at our hospital since 1965. This is the second largest series reported to date. Children who had neurogenic bladders or any structural abnormalities of the urinary tract other than vesicoureteral reflex were excluded. The study group included 36 girls and 1 boy. The average age at first detection of renal scars was 5.7 years. Acute pyelonephritic episodes, which were treated early and aggressively, infrequently led to renal scarring. However, the initial prolonged or poorly treated episode of acute pyelonephritis was followed invariably by the development of renal scarring. The severity of renal scarring was related to the grade of vesicoureteral reflux (p less than 0.05), although some scars did develop in the absence of reflux. Neither the shape and position of the ureteral orifice nor the ureteral tunnel length correlated with the severity of renal scarring. Treatment with prophylactic antibiotics may have lessened the severity of renal scarring (0.1 less than p less than 0.2) but treatment with reimplantation surgery did not appear to alter the course of renal scarring. This study suggests that the key to the prevention of renal scarring is the early and aggressive treatment of acute pyelonephritis.

Occult Spinal Dysraphism: Clinical and Urodynamic Outcome after Division of the Filum Terminale

A highly select group of 31 patients presenting with urinary incontinence failed to respond to conservative management and were found to have unstable bladders and spina bifida occulta. After thorough evaluation they were suspected of having neurogenic bladder dysfunction possibly due to a tethered cord. Following division of the filum terminale daytime incontinence resolved in 72%, urodynamic detrusor hyperreflexia disappeared in 59% and bladder compliance improved in 66% of the patients. The operation was well tolerated and did not result in any neurological complications. The clinical, radiological and urodynamic characteristics of these patients before and after treatment are reported.

Loss of Elasticity in Dysfunctional Bladders: Urodynamic and Histochemical Correlation

To store adequate volumes of urine at low safe pressures an elastic bladder wall is required. We developed 2 new techniques to measure this ability in our urodynamic laboratory: pressure specific bladder volume, which measures the bladder capacity at a given pressure, and dynamic analysis of bladder compliance. Recently, morphometric and histochemical techniques have been used to determine the relative volume of connective tissue in the bladder wall and to measure the 2 major types (I and III) of collagen within the bladder wall. These methods quantitate 3 parameters of bladder ultrastructure: 1) relative volume of per cent connective tissue, 2) ratio of connective tissue to smooth muscle and 3) ratio of type III to type I collagen. These parameters have been shown to be abnormally elevated in patients with dysfunctional bladders compared to normals. The purpose of the study was to describe the ultrastructural changes that occur in the wall of dysfunctional bladders and to determine the ability of these new urodynamic techniques to detect reliably the clinical effect of these histological changes. The study included 29 consecutive patients with dysfunctional bladders necessitating bladder augmentation. All patients had upper tract changes and/or were incontinent despite treatment with clean intermittent catheterization and pharmacotherapy. Preoperative urodynamic evaluation included measurement of the total bladder capacity, pressure specific bladder volume and dynamic analysis of bladder compliance. Full thickness bladder biopsies were obtained from the dome of the bladders during augmentation. The per cent connective tissue and the ratio of connective tissue to smooth muscle were determined for all patients, and 4 unselected patients from this group had the ratio of type III to type I collagen determined. These histological results were compared to previously established normal values. All 29 patients had a decreased pressure specific bladder volume and dynamic analysis of bladder compliance, whereas 9 had a normal total bladder capacity. The per cent connective tissue was 35.19 +/- 2.84 and ratio of connective tissue to smooth muscle was 0.60 +/- 0.08 compared to normal values of 10.6 +/- 0.020 and 0.131 +/- 0.021, respectively (p < 0.05). Ratio of type III to type I collagen was also significantly elevated in the 4 samples analyzed (30.53 +/- 1.37 versus 24.00 +/- 2.50, p < 0.05). We conclude that poor storage function of poorly compliant bladders is secondary to an alteration in the connective tissue content of the bladder wall. Furthermore, these pathological ultrastructural changes are universally reflected by an abnormally low pressure specific bladder volume and dynamic analysis of bladder compliance. This strong association validates the use of these parameters and suggests that they are urodynamic indicators of a loss of elasticity in bladder wall.

What volume can a child normally store in the bladder at a safe pressure

To determine what volume a child can normally store in the bladder at a safe pressure 923 pediatric urodynamic studies were reviewed, and 69 examinations done on 17 boys and 52 girls were considered normal. Patient ages were recorded and body surface areas were calculated. A continuous intermediate flow water cystometrogram had been performed. Total bladder capacity in milliliters, full resting pressures (cm. water), and the volumes (milliliters) and percentages of the total bladder capacity stored at detrusor pressures of less than 10, 20, 30 and 35 cm. water were measured. We found that 98.1% of the total bladder capacity could be stored at a detrusor pressure of less than 20 cm. water in more than 95% of the children independently of age or body surface area and 99.9% could be stored at a detrusor pressure of less than 30 cm. water. An approximation of the minimal acceptable total bladder capacity for age can be calculated by 16(age) + 70 in ml. According to our results, we proposed criteria for good storage characteristics of the bladder in children.

Factors Influencing Patient and Graft Survival in 300 Cadaveric Pediatric Renal Transplants

We reviewed the results of 300 cadaveric pediatric renal transplantations performed at our institution. The procedures provided significant survival and improvement of the quality of life in the majority of children. Recipient and graft survival was better in patients more than 5 years old than in younger children. Early nontechnical thrombosis was a major specific problem in young recipients. The original disease did affect graft survival. Uncorrected congenital bladder storage and micturition inefficiency adversely affected graft survival.

Intestinal metaplasia is not a strong risk factor for bladder cancer : Study of 53 cases with long-term follow-up

OBJECTIVES Intestinal metaplasia often coexists with adenocarcinoma of the urinary bladder, suggesting to some investigators that it is premalignant. However, the natural history and long-term outcome of intestinal metaplasia in isolation are unknown. We report 53 cases of intestinal metaplasia of the urinary bladder followed for more than 10 years. METHODS We reviewed the Mayo Clinic surgical pathology files between 1926 and 1996 and all patients with exstrophic bladder recorded in the files of the Hospital for Sick Children (Toronto, Ontario, Canada) and Dallas Childrens Hospital (Dallas, Texas) between 1953 and 1987, and identified all patients with intestinal metaplasia of the bladder. RESULTS A total of 53 cases were identified from both series, and none of the patients developed adenocarcinoma of the bladder. The Mayo Clinic series consisted of 24 patients. Nineteen of the 24 (79.1%) were alive without evidence of cancer (median follow-up 14 years, range 0.9 to 53), and 5 patients died of intercurrent disease (at 0.9, 4, 8, 11, and 53 years after diagnosis) without evidence of bladder cancer. The Dallas Childrens Hospital and the Hospital for Sick Children series consisted of 29 patients. Twenty-seven of the 29 (93.1%) were alive without evidence of cancer (median follow-up 13 years, range 3 to 23.9). Two patients died of trauma (at 10.9 and 12 years after diagnosis) and at autopsy had no evidence of bladder cancer. CONCLUSIONS Intestinal metaplasia of the urinary bladder is not a strong risk factor for adenocarcinoma or urothelial cancer.

Outcome analysis of Mitrofanoff principle applications using appendix and ureter to umbilical and lower quadrant stomal sites.

PURPOSE We compared the indications for and results of application of the Mitrofanoff principle using appendix and ureter to umbilical and lower quadrant stomal sites. MATERIAL AND METHODS We created continent catheterizable conduits in 60 patients 3 days to 20 years old (mean age 8.8 years). The primary indication was refractory urinary incontinence associated with bladder or cloacal exstrophy, or anomalies in 31 cases. We constructed 38 umbilical (all appendix) and 22 lower quadrant (10 appendix and 12 ureter) stomas. Mean followup was 3 years. RESULTS We preferred the umbilicus as a stomal site for its cosmetic value. The most common indication for a lower quadrant stomal site was preservation of the retroperitoneal course of the ureter. The stomal stenosis rate was 13 and 4% in patients with umbilical and lower quadrant stomas, respectively. We preferred the appendix as a conduit due to availability. Indications for the ureter as a catheterizable conduit were absence of an adequate appendix or presence of a healthy ureter after nephrectomy. The appendiceal and ureteral conduits were catheterizable in 94 and 84% of patients, respectively, and continence was achieved in 97%. CONCLUSIONS In a complex group of patients with incontinence application of the Mitrofanoff principle yielded good results for either combination of stomal site or catheterizable conduit. Appendicovesicostomy to the umbilicus remains our preferred procedure.