Israel Medical Association Journal

Background: Obstruction of urine outflow can result from mechanical blockade as well as from functional defects. In adults, urinary tract obstruction is due mainly to acquired defects, such as pelvic tumors, calculi, and urethral stricture. In childhood it is mostly due to congenital malformations. In this article we present two rare cases of acute obstructive renal failure that presented with hydronephrosis. These cases underline the wide range of causes that may lead to this clinical feature. 

Background: Multiple primary malignancies are increasingly being detected among cancer patients. Objectives: To investigate the co-occurrence of primary bladder cancer and primary lung cancer, two established smoking-related neoplasms characteristically associated with increased risk of secondary cancers.

Methods: A retrospective search of the patient registry in our institution identified 25 patients (23 men and two women) who were diagnosed with both bladder cancer and lung cancer during the period 1990–2005. Medical records were reviewed and clinical and pathological data were extracted.

Results: In 21 patients (84%) bladder cancer was the first primary tumor and in 4 (16%) the second primary tumor. More than 90% of the patients had a history of smoking. Mean smoking exposure was 62.1 pack years (range 30–120). All bladder cancers were transitional cell carcinomas with the majority being superficial at presentation. Most lung cancers were of the non-small cell type. Second primary lung cancers were significantly more advanced at diagnosis. Overall, mean follow-up was 105.8 months (range 6–288). Seven patients (28%) were alive at the time of evaluation; 68% died of lung cancer, while none died of bladder cancer.

Conclusions: Second primary lung cancer may occur in patients with bladder carcinoma and vice versa. In view of the relatively frequent involvement of the genitourinary tract as a site of multiple primary tumors, urologists may have a key role in the detection of second primary tumors arising in the genitourinary tract, or second primary tumors that occur in patients with primary genitourinary tract malignancies.
 

Background: Ion Channel Innovations has developed a gene transfer product, ftMaxi-K, and has begun clinical trials to investigate the effect of increased expression of Maxi-K channels in the smooth muscle of the penis or bladder in patients with erectile dysfunction and those with overactive bladder. The primary function of K channels is to modulate Ca⁺⁺ influx through Ca-channels (i.e., L-type, voltage-dependent). The amount of Ca⁺⁺ that enters the cell through these channels is a major determinant of the free intracellular calcium levels inside the smooth muscle cell, which in turn determines the degree of smooth muscle cell contraction. Increased Maxi-K channel activity is associated with smooth muscle cell relaxation, resulting in, for example, penile erection and detrussor muscle relaxation. A phase I clinical trial that used dMaxi-K has been completed and a similar trial to assess safety of the transfer for overactive bladder is about to begin.

Objectives: To assess the safety and tolerability of escalating dMaxi-K doses by clinical evaluations and laboratory tests, and to measure efficacy objectives by means of the International Index of Erectile Function scale.

Methods: In the erectile dysfunction trial 11 patients with moderate to severe erectile dysfunction were given a single-dose corpus cavernosum injection of dMaxi-K, a "naked" DMA plasmid carrying the human cDNA encoding for the gene for the a, or pore-forming, subunit of the human smooth muscle Maxi-K channel, hSIo. Three patients each were given 500,1000, and 5000 pg and two patients were given 7500 pg doses of ftMaxi-K and followed for 24 weeks. Patient responses were validated by partner responses.

Results: There were no serious adverse events and no dose-related adverse events attributed to gene transfer for any patient at any dose or study visit. No clinically significant changes from baseline were seen in physical evaluations (general and genitourinary), hematology, chemistry and hormone analyses, or in cardiac events evaluated by repeated electrocardiograms. Importantly, no plasmid was detected in the semen of patients at any time after the injections. Patients given the two highest doses of dMaxi-K had apparent sustained improvements in erectile function as indicated by improved IIEF-EF domain scores over the length of the study. One patient given 5000 (jg and one given 7500 [jg reported EF category improvements that were highly clinically significant and were also maintained through the 24 weeks of study.
Conclusions: Efficacy conclusions cannot be drawn from results of a phase 1 trial with no control group. However, the promising primary safety outcomes of the study and preliminary indications of effectiveness provide evidence that ftMaxi-K gene transfer is a viable approach to the treatment of erectile dysfunction and other smooth muscle diseases with targeted access

Background: Bladder exstrophy is a severe congenital defect that requires a multidisciplinary treatment approach. Soft tissue repair may be successful during the first few days after birth but a combination of pelvic osteotomies and bladder reconstruction is necessary later in life. The combination of externally fixed anterior and posterior osteotomies has biomechanical advantages over previous techniques for achieving primary bladder closure.

Objectives: To describe our experience with a combined vertical and horizontal pelvic osteotomy approach for the repair of bladder exstrophy.

Methods: Four children underwent bladder exstrophy closure; the mean age at surgery was 19 months (range 9–33 months)... We stabilized the osteotomies with a small Synthes AO external fixator, 4.0 mm rod diameter.

Results: All four patients had successful bladder repair with no dehiscence; two of them achieved partial continence, and bladder neck reconstruction is planned for the other two. Three of the four patients sustained neurologic injury; two completely recovered, and the third continues to suffer from right drop foot. The average follow-up was 39 months (range 10–60 months).

Conclusions: Vertical and horizontal pelvic osteotomies stabilized by external fixator and bladder repair is an effective treatment for bladder exstrophy.

Background: Carcinoma of the gallbladder is diagnosed in 0.3–1.5% of all cholecystectomy specimens.

Objectives: To establish the overall rate of gallbladder carcinoma and unexpected gallbladder carcinoma based on our experience.

Methods: We retrospectively evaluated all consecutive cholecystectomies performed in our ward during a 6 year period in order to determine the incidence of gallbladder carcinoma and to identify common characteristics of this particular group of patients.

Results: Of the 1,697 cholecystectomies performed in our ward during the 6 years, gallbladder carcinoma was diagnosed in six patients (0.35%), but was not suspected prior to surgery in any of them. In accordance with the literature, the occurrence in women (5/6) was higher than in men (1/6). The mean age was 70 years (range 55–90). The most common symptom was abdominal pain; the majority (5/6) had cholelithiasis, and the pathologic report confirmed the diagnosis of adenocarcinoma in all six patients.

Conclusions: The overall incidence of unsuspected gallbladder carcinoma in our series was 0.35%. We could not find any common characteristics for this particular group of patients when compared to patients with non-malignant pathology.

Background: The bladder tumor antigen stat is a simple and fast one-step immunochromatographic assay for the detection of bladder tumor-associated antigen in urine.

Objectives: To evaluate the BTA[1] stat in non-bladder cancer patients in order to identify the categories contributing to its low specificity.

Methods: A single voided urine sample was collected from 45 patients treated in the urology clinic for conditions not related to bladder cancer. Each urine sample was examined by BTA stat test and cytology.

Results: The overall specificity of the BTA stat test was 44%, which was significantly lower than that of urine cytology, 90%. The false positive rates for BTA stat test vary among the different clinical categories, being highest in cases of urinary tract calculi (90%), and benign prostatic hypertrophy (73%). Exclusion of these categories from data analysis improved BTA stat specificity to 66%.

Conclusions: Clinical categories contributing to low BTA stat specificity can be identified, and their exclusion improves the specificity of this test.