Re-evaluation of histological findings after colocystoplasty and gastrocystoplasty.

INTRODUCTION: The potential of malignant transformation and its risk factors after bladder augmentation performed in childhood are still unknown. The necessity of surveillance cystoscopies and biopsies has been questioned in the past decade. OBJECTIVE: In a previous study, the authors did not detect any malignancy after colocystoplasty (CCP) or gastrocystoplasty (GCP) during the short-term follow-up, however, various alterations of the mucosa were found. A correlation between the nature of histological changes and the frequency of bacterial colonization after CCP were also found. The authors hypothesized that a longer-term follow-up of their patients would reveal an increase in pathological change or show stronger association between the histological alteration, bacterial colonization, and/or stone formation. PATIENTS AND METHODS: Thirty-five patients (20 cases of colocystoplasties - CCPs; 15 cases of gastrocystoplasties - GCPs) participated in the study published in 2002. All patients were followed biannually with endoscopic assessment and biopsies. Two independent pathologists, evaluated regular biopsies from the native bladder, from the segment used for augmentation and from the anastomosis line. Etiology, frequency of positive urine cultures, and stone events were recorded and compared with histological findings between groups and with the previously published results. RESULTS: Continuous surveillance allowed the follow-up of 30 patients (CCP 19/20, GCP 11/15) for 20 and 15 years. No malignancies were identified. Results of biopsies showed significant difference between groups (summarized in the tables). Chronic inflammatory changes were found following both types of augmentations, but they were more common in the urothelium following GCP and more common in the colonic mucosa following CCP. The rate of metaplastic lesions was higher after gastrocystoplasty (GCP). Significant association was found between the etiologic factor and the nature of histological change after CCP, as metaplastic lesions occurred only in patients with bladder exstrophy. Stones occurred more frequently in exstrophy patients as well. The nature of the histological changes did not correlate with positive urine cultures in either of the groups. Significantly higher incidence of bacterial colonization and stone occurrence were found after CCP. CONCLUSIONS: Long-term follow-up of the patients failed to reveal an increase in pathological changes, and no malignancies were observed. According to the results of this study, etiology of bladder dysfunction and the type of augmentation might influence the histological alterations after augmentation cystoplasty. The efficiency of surveillance cystoscopies and biopsies are low. The present data suggest that surveillance cystoscopy and biopsy should not be routinely performed, and should be done only if the symptoms are suspicious for malignancy.

Long-term histological and mucin alterations in the neobladder mucosa following urinary bladder augmentation or substitution with gastrointestinal segment.

INTRODUCTION: Bladder augmentation is widely used to treat otherwise unmanageable urinary incontinence. However, it is associated with a large number of complications, of which tumor formation is the most severe. Mucin proteins and MUC genes are linked, among others, to malignancies of the urinary bladder and the gastrointestinal system. OBJECTIVE: To investigate histological alterations as well as changes in expression of MUC1 and MUC2 genes and proteins following different types of urinary bladder augmentation or substitution performed in children and adolescents. PATIENTS AND METHODS: Between 1988 and 2013, 91 patients underwent urinary bladder augmentation or substitution at the study institute. Patients were included on whom cystoplasty had been performed 4 years previously or earlier, and could have been followed-up prospectively. Thus, 54 patients were involved in the study. In eight patients gastrocystoplasty was performed, in 17 patients ileocystoplasty, and in 22 patients colocystoplasty. Seven patients underwent bladder substitution using a colonic-segment. Biopsies were taken via cystoscopy from the native bladder, from the gastrointestinal segment used for augmentation, and from the anastomotic line between these two. One part of the samples was fixed in formaldehyde for routine histological processing. The other part of the biopsies was embedded into OCT medium, then cryosectioned and fluorescently double-immunostained for MUC1 and MUC2 proteins. Samples from the microscopically dysplastic lesions and from the 15-year-old or older biopsies were processed by laser capture microdissection, and then real-time PCR was done. Data were statistically analyzed by ANOVA and ordinary least squares regression tests. RESULTS: One adenocarcinoma was found in a female patient, 11 years after colocystoplasty. There were no significant changes in the level of MUC1 and MUC2 proteins and gene expression in the urothelium and in the gastrointestinal segment used for augmentation following ileocystoplasty and gastrocystoplasty. Significant increase in MUC1 and decrease in MUC2 protein levels were detected following colocystoplasty in the large bowel segment used for augmentation, both with qualitative and quantitative methods (p < 0.05) (Figure). The uroepithelium showed no significant change. RT-PCR revealed progressive increase in MUC1 gene expression and decrease in MUC2 gene expression after colocystoplasty in the course of time. It also showed highly increased MUC1 gene expression and decreased MUC2 gene expression in the samples of patients. CONCLUSIONS: Alterations in gene expression of MUC1 and MUC2 might serve as promising markers for early detection of histological changes after colocystoplasty.

Composite urinary reservoir in dogs: histological findings.

PURPOSE: This animal study was designed to investigate whether the composite urinary reservoir might lessen the premalignant histological alterations observed after bladder augmentation performed with a gastric segment or large bowel. MATERIALS AND METHODS: Composite urinary reservoirs were created using gastric and colonic segments simultaneously in 8, 3-month-old female beagle dogs by augmenting half the native bladder. Two dogs with gastrocystoplasty and 2 with colocystoplasty served as controls. Biopsies were taken from the native bladder, and the gastric and colonic segments at augmentation, and endoscopically 4 and 8 months postoperatively. The dogs were sacrificed and open biopsied 12 months postoperatively. Tissue specimens were examined with routine hematoxylin and eosin, reaction and immunohistological staining for PCNA. RESULTS: At the creation of composite reservoir and gastrocoloplasty or colocystoplasty all specimens showed normal histology. At 12 months postoperatively dysplasia was found in 1 gastric segment, 2 native bladders and 3 colonic segments in the composite reservoir group. There was a single carcinoma in situ in 1 gastric segment in the composite reservoir group. In the control groups 1 colonic segment and 1 native bladder dysplasia were detected at the end of 12-month followup. There was an in situ carcinoma in 1 gastric segment in the composite reservoir. CONCLUSIONS: A composite reservoir did not decrease premalignant changes in dogs during 12 months of followup. Laboratory investigations, molecular studies and longer followup are needed to approach the question of early malignant alterations after augmentation cystoplasty in animals and patients.

Combination of vesicoureteric reflux and vesicoureteric junction obstruction.

OBJECTIVE: This study analysed the association of vesicoureteric reflux (VUR) and vesicoureteric junction obstruction (VUJO) requiring surgical interventions in infants and children. MATERIAL AND METHODS: Over 30 years (1975-2004) 423 infants and children were operated on because of VUR, 163 owing to VUJO and 25 patients (33 ureters) with a combination of VUR and obstruction of the vesicoureteric junction on the same side. For both pathological entities ureteral reimplantation was performed along with excision of the narrowed and refluxing distal ureteric segment. The age of patients at surgery ranged from 3 months to 11 years (average 2.6 years). The female to male ratio was 1.4:1. RESULTS: Out of the 25 patients (33 ureters), both entities were diagnosed before surgery in 10 of them (15 ureters). In 15 cases (18 ureters), only the VUR was preoperatively diagnosed; however, the VUJO was only suspected and confirmed during the operation. In one refluxing ureter, the obstruction was not diagnosed during subureteric endoscopic injection of the orifice. In five of the 33 ureters, redo reimplantation was necessary because of obstruction (four ureters) or reflux (one ureter). CONCLUSIONS: A combination of VUR and VUJO should be taken into consideration in a patient with proven reflux, where the ureter is dilated and tortuous and following urination the hydronephrosis and hydroureter persist or slowly decrease. In such cases long-term prophylaxis and endoscopic treatment are contraindicated but open surgery (reimplantation) is recommended.

Quality of life: urinary bladder augmentation or substitution in children.

PURPOSE: Bladder augmentation and substitution has been assumed to improve health-related quality of life in patients with urinary incontinence. This study was performed to elicit an evidence base for or against the above hypothesis. METHODS: Between 1988 and 2006, 67 bladder augmentations and 7 bladder substitutions were performed at our institute. Inclusion criteria for the cross-sectional study were a postoperative period of more than 1 year and an age of at least 10 years at the time of operation. A multimodality treatment-specific questionnaire (comprising 38 questions) was designed and sent to 61 patients. Quality of life was investigated in all patients and between the groups of patients with meningomyelocele (Group A) versus bladder exstrophy (Group B), patients, who are catheterizing themselves via urethra (Group C) versus stoma (Group D) and patients who are using (Group E) versus not using wheelchair (Group F) following the surgery. For the statistical analysis Students t test, Wilcoxon signed rank test and correlation analysis were used. RESULTS: A significant overall improvement was found in patients quality of life following this surgery (P < 0.05). Ninety percent of patients would prefer again bladder augmentation or substitution to their previous state. Patients with meningomyelocele are changing pads or diapers more frequently than exstrophy patients because of their bowel problems postoperatively. Quality of life improved better in patients performing CIC via stoma than in patients who perform it via their native urethra (P < 0.05). Outcomes were independent of patients age and of the post-augmentation time to assessment (P < 0.05). CONCLUSIONS: Bladder augmentation or substitution significantly improved the health-related quality of life in children and young adolescents taking part in the study. The authors are planning a prospective long-term follow-up of the patients (longitudinal study) to validate the results.

End-of-life decision before and after birth: changing ethical considerations.

Despite the dramatic improvement in the outcome of somatically handicapped neonates, vexing ethical issues remain. In which fetuses would termination be indicated? In which neonates are the malformations so serious that surgery and intensive care should not be initiated (withholding or not starting treatment)? Conversely, in which neonates should the initiated treatment be stopped (withdrawal of treatment)? These questions pose huge medical, legal, ethical, moral, and financial problems for doctors, lawyers, ethicists, and families. Fetuses and neonates with congenital anomalies can be divided into 6 groups: 1, those who have the potential for total recovery; 2, those with anomalies that would allow for a nearly normal life; 3, those with malformations requiring permanent supervision and/or medical care; 4, those with somatic rest defect and subnormal mental development; 5, those with serious somatic and mental damage; and 6, those with anomalies that are incompatible with life. The decision making should be tailored to each of these groups. The pediatric surgeon, besides taking into consideration the quantity and quality of the rescued life, should lower the anxiety of the parents, should follow the morals of a civilized society, should act according to the law, and finally, should convince himself to be a solution to a problem and not to be a cause of any.

Role of the Teflon deposit in the recurrence of vesicoureteral reflux.

A relationship between the Teflon deposit, visible with ultrasound, and long-term success of subureteric Teflon injection (STING) treatment was investigated. The study included only those patients with primary vesicoureteral reflux (VUR), in whom the reflux had disappeared and the Teflon deposits were visible 6 weeks following STING treatment. Cessation of VUR was proven by voiding cysto-urethrography (VCUG) in 99 patients (143 ureters). Average follow-up time was 9 (4-12) years. Patients were divided into two groups: group I, deposits visible with ultrasound [deposit (+)], and group II, no visible deposits at the end of the follow-up period [deposit (-)]. Reflux recurrence, the occurrence of urinary tract infection (UTI), and pyelonephritis were investigated, and technetium scintigraphy scans were examined. The deposit (+) group included 43 patients (65 ureters), and the deposit (-) group contained 56 patients (78 ureters). In the deposit (+) group there were no recurrences of VUR; however, 17 recurrences were found in the deposit (-) group (P < 0.05). Dimercaptosuccinic acid (DMSA) scintigraphy scans and occurrence of UTI showed significant difference between the groups (P < 0.05). A close relationship was found between the disappearance of the Teflon deposit and the recurrence of VUR. Disappearance of the Teflon deposit and repeated bacteriuria is a warning sign of the recurrence of VUR; therefore, VCUG might be warranted for these patients.

A therapeutic method for failed bladder augmentation in children: re-augmentation.

OBJECTIVE: To investigate the causes leading to the deterioration of previously successful bladder augmentation and to evaluate the efficacy of re-augmentation. PATIENTS AND METHODS: Between 1988 and 2004, 136 bladder augmentations were performed in two paediatric urological units in Hungary and Turkey. Re-augmentation was necessary in two patients after colocystoplasty and in three after gastrocystoplasty. A secondary augmentation was not required in any patients after ileocystoplasty. The clinical data of these five patients were evaluated. RESULTS: On the basis of the clinical signs and urodynamic studies, re-augmentation was performed 2-7 years after the initial augmentation cystoplasties. Anticholinergic therapy given before re-augmentation did not improve bladder capacity, intravesical pressure and/or bladder compliance. An ileal or sigmoid segment was used for the secondary augmentation. After re-augmentation, all five patients became continent, and showed marked improvement in their urodynamic parameters at a mean (range) follow-up of 6.8 (2-10) years. CONCLUSION: A decreased bladder capacity and/or compliance and increased bladder pressure after successful augmentation cystoplasty might be the result of: (i) impairment of the blood supply to the large bowel or gastric segment used for augmentation; or (ii) bowel mass contractions. Ileocystoplasty seems to be the "first-line" of choice for primary augmentation. Re-augmentation with a bowel segment is a suitable treatment if conservative treatment fails. Regular urodynamic investigations are needed for early detection of malfunction of the augmented bladder, and advising therapy.

Histologic findings after gastrocystoplasty in rabbits.

PURPOSE: The aim of this study was to investigate the long-term histologic changes after bladder augmentation with gastric segment in an animal subject. MATERIALS AND METHODS: Gastrocystoplasty was performed in 13 young, 3-month-old male rabbits. Open biopsies were taken from the native bladder and the gastric segment preoperatively and at 3, 6, and 12 months postoperatively. Sections were examined with H&E and periodic acid-Schiff (PAS) staining. Indirect immune peroxidase method was additionally applied to detect the carcinoembrionic antigen, the proliferative activity, and the gene for the tumor protein p53 in the epithelium. RESULTS: On the native bladder, at the 3-month follow-up, polyps, mucosal edema, submucosal fibrosis, and squamous cell metaplasia were detected, which did not change during the follow-up. On the gastric segment, at the 3-month follow-up, parietal cell hyperplasia and inflammatory mucosal overgrowth were detected; at the 6-month follow-up, inflammation or atrophy of the gastric mucosa and colonic-type metaplasia was found. These alterations remained unchanged during later course of follow-up. Neither dysplasia nor malignancy was observed during the 12-month follow-up. CONCLUSIONS: The present study supports the clinical observations of low cancer risk after gastrocystoplasty and may indicate different effect of gastric secretion on uroepithelium and that of urine on gastric mucosa.

A long-term follow-up of five patients with atresia of the common bile duct.

BACKGROUND/PURPOSE: Description of the long-term follow-up of 5 patients operated on for atresia of the common bile duct. METHODS: During a 25-year period (1960 to 1985) 45 infants underwent surgical exploration for biliary atresia (BA), of which, 5 (11.1%) were found to have atresia of the common bile duct. The children were followed up into adult life by pediatric surgeons, pediatricians, and later, adult hepatologists with the range of 19 to 36 years. Liver function tests, histology, complications, and somatic development (including sexual maturation and mental development) were obtained continuously. RESULTS: Liver function test results were normal in all but 1 patient. Repeated ultrasound scan and postoperative liver biopsies were normal in 2 patients and moderately and mildly abnormal in 3 patients, respectively, suggesting hepatic fibrosis. HIDA hepatic scans in all but 1 patient showed prompt uptake by the liver with passage into the bowel within 30 minutes. Endoscopic retrograde cholangiography (ERCP; 1 patient) and duodenography (4 patients) showed, at most, mild reflux of contrast material into the extra- or intrahepatic bile ducts. One patient with cholecysto-duodenostomy had 3 episodes of clinically proven ascending cholangitis. All 5 patients had normal physical growth and mental development, they are all age-appropriate schooled, and they are working and living a normal life. CONCLUSIONS: Long-term favorable outcome has been suggested to be more influenced by anatomic and biological features rather than the surgical correction. The hypothesis is supported that BA is not a static congenital malformation but a progressive inflammatory panductular obliterative disease of the bile ducts starting in the antenatal period, which might cease, either early at birth or any time in infancy. The destructive inflammatory process might involve only the distal part of the extrahepatic bile duct causing obstruction and leaving the proximal ducts patent.

Extremely long frenulum leading to a giant preputial sac associated with concealed penis.

We describe a case involving an abnormally long frenulum leading to a giant preputial sac on micturition associated with a concealed penis. The diagnosis, differential diagnosis and surgical correction are detailed.

Seromuscular gastrocystoplasty in dogs.

INTRODUCTION: The aim of this study was to investigate the feasibility of seromuscular gastrocystoplasty (SGCP) in an animal model and to compare it to conventional gastrocystoplasty (CGCP). MATERIALS AND METHODS: CGCP and SGCP (using gastric segments without mucosa) were each performed in 6 dogs. In both procedures, two-thirds of the dome of the bladder were excised and the gastric segment anastomosed to the bladder remnant. Cystography, cystomanometry, measurements of urine pH, and gross and microscopic pathological studies were carried out preoperatively, and postoperatively, at 6 and 12 weeks. RESULTS: All seromuscular gastric segments proved viable, and 6 weeks after the operation they were covered by a thin layer of transitional epithelium, which had gradually thickened by the end of the 12-week follow-up. There was no difference in bladder capacity and compliance between the two groups, however, fasting urinary pH values were higher (less acidic) in the SGCP group. CONCLUSIONS: Stripping off the mucosa of the gastric segment appears to stop hydrochloric acid secretion, thereby lessening the possible risk of ulceration, perforation, dysuria-haematuria, metaplasia and malignancy. The uroepithelium overgrowth of the seromuscular gastric segments might provide a more physiological neo-bladder than when using full-thickness gastrocystoplasty.

Long-term follow-up of cancer in neonates and infants: a national survey of 142 patients.

To determine the mortality and survival rates, side effects of surgery and adjuvant chemo- and radiotherapy, somatic development, and fertility, the data of 142 patients under the age of 1 year operated upon for solid malignant tumors from 1975 through 1983 were analyzed. The follow-up period ranged from 16 to 25 years (mean 20); 79 patients survived. The male/female ratio of the survivors was 51/28. Investigations were based on the Hungarian Tumor Registry, personal interviews with the patients and their parents, and detailed questionnaires. Fifty-one patients died, 44 of them before the age of 3 years; 13 were lost to follow-up. Of the 79 survivors, 48 had abdominal and 31 extra-abdominal tumors (35 neuroblastomas, 21 renal tumors, 15 soft-tissue sarcomas, 5 gonadal tumors, 2 sacrococcygeal carcinomas, 1 hepatic tumor). Side effects of surgical intervention included partial urinary incontinence (2), partial fecal incontinence (1), intestinal obstruction (2), nerve injury (1), thorax deformity (4), and scar formation resulting in psychological problems (12). Chemotherapy alone (41 patients) resulted in side effects in 19 patients, radio- and chemotherapy in combination (23) caused side effects in 20. Fifteen patients did not receive adjuvant therapy. The most serious late side effects were 24 spinal deformities, one-half of them severe, breast underdevelopment, muscular deformity, and renal damage. In 19 patients more then one side effect was detected. Height and weight gain decreased ( P < 0.01 and <0.05, respectively) in the first 8-10 years of follow-up and accelerated significantly ( P < 0.05 and <0.05, respectively) in the second half of follow-up. The short follow-up time (16-25 years) permitted only limited analysis of infertility. Whenever possible, surgical excision should be the treatment of choice. No routine aggressive chemotherapy is indicated. Radiation therapy, which frequently results in long-term musculoskeletal morbidity, should be avoided. Catch-up somatic development occurred in the second part of the follow-up period.