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Bladder augmentation in childhood: metabolic consequences and surgical complications – Review and own investigations

Andrew B. Pinter, Peter Vajda, Zsolt Juhasz

Department of Paediatrics, Medical Faculty of Pécs University

Pécs, Hungary

 

Abstract

Bladder augmentation is an invaluable tool for paediatric surgeons interested in paediatric urology, and paediatric urologists for both the protection of upper urinary tract and achievement of urinary continence. However, it remains a major surgical undertaking with significant morbidity. This paper reviews the pathophysiology of some of the most common metabolic consequences and the most frequent surgical complications of bladder augmentation. Furthermore, it summarizes the authors’ investigations regarding this topic.

Key words: bladder augmentation, metabolic consequences, surgical complications, animal experiments


Correspondence:

Andrew B. Pinter

Department of Paediatrics, Medical Faculty, University of Pécs

Hungary, 7623 Pécs, Hungary József A. u. 7.

e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.

 

Historical background

The use of other than urinary tissue to create a reservoir for urine is not a new concept. Uretero-sigmoidostomy was used to a child with bladder extrophy over 150 years ago (1), however, most of children with bladder extrophy, severe posterior urethral valves, cloacal malformations and/or myelodysplasia were primary treated with urinary diversion (2,3).

A new area of management of children previously diverted was initiated by Hendren [4). He found that these children could be undiverted if the primary pathology could be corrected (e.g. fulguration of urethral valves, correction of severe reflux, tapering of megaureters) (5). In some of these cases bladder augmentation with bowel is also described (6).

The application of augmentation cystoplasty in children could not be realized until Lapides et al (7) showed the effectiveness of Clean Intermittent Catheterization (CIC) to empty the augmented bladder. Application of CIC totally changed the management of child with abnormal bladder function with or without augmentation.

Review of literature

In the first part of this study we briefly discuss the most frequent metabolic changes following bladder augmentation.

Metabolic consequences

Incorporation of bowel segments in the genitourinary tract is associated with several metabolic consequences and late surgical complications (8, 9). The gastrointestinal tract is a relatively poor substitute for urothelium and its semipermeability permits non-physiological fluid and electrolyte abnormalities (secretion and absorption).

Material used for bladder augmentation

a.parts of the alimentary tract

- stomach

- large bowel

- small bowel

b. urothelial segments

- ureter

- auto-augmentation

- auto-augmentation combined with seromuscular flap

Augmentation using gastrointestinal segment

Gastrocystoplasty

The use of gastric segment for augmentation cystoplasty is not common, however in certain specific instances stomach can be valuable. Surgically, the stomach is relatively thick and easy to work with it. The metabolic advantages of gastric cystoplasty are intestinal sparing and prevention of short bowel syndrome, decreased occurrence of hyperchloremic metabolic acidosis and decreased mucous production, lower rates of urine infection and stone formation.

Patients with renal insufficiency and chronic acidosis may benefit from gastrocystoplasty because of the ability of the stomach to secrete acid (10). However, the use of stomach for bladder augmentation is not without consequences. Fluid, potassium and chloride loses may develop, resulting in hypochloremic, hypokalemic metabolic alkalosis. When patients present with symptoms (lethargy, mental status changes, compensatory (respiratory acidosis that develops in response to metabolic alkalosis (11), electrolyte and fluid repletion are the primary treatment.

A potentially painful complication of gastrocystoplasty is haematuria-dysuria syndrome, a complex that includes dysuria, genital skin irritation and excoration, bladder spasms, suprapubic and/or urethral pain and gross haematuria. The aetiology is likely related to chemical irritation of the urothelium when exposed to gastric acid. Treatment includes increased fluid intake, correction of potassium abnormalities, use of histamine-2 blockers, anticholinergic agents and omeprazole, and at times removal of the gastric segment (12).

Use of small and large bowel

The major function of intact small and large bowel is to absorb food, fluid, and electrolytes. When urine is stored in the bowel for prolonged periods there is increased absorption of urinary solutes, which increases the risk of metabolic derangement. In patients with normal renal function, serum electrolytes are usually unaffected by enterocystoplasty. However, in patients with impaired renal function metabolic acidosis can be profound.

Ileocystoplasty

Advantage of use of ileum for augmentation is the abundant mesenteric blood supply of the small bowel, moderate mucous production compared to the colon and less severe associated metabolic complications compared to stomach and colon. Contraindications of use of ileum are short gut syndrome, inflammatory bowel disease, pelvic and abdominal irradiation and renal insufficiency. Ileal segments are associated with some disadvantages, like occasional hyperchloremic, hypokalemic metabolic acidosis, vitamin B12 deficiency, sometimes diarrhea and steatorrhea. Creation of submucosal tunnels for ureteral implantation is more difficult into the wall of ileum than in case of large bowel (tenia).

Colocystoplasty

Enterocystoplasty using colon is complicated by several functional and anatomical characteristics unique to the large bowel. Shorter mesenteries can make the mobilisation and detubularisation of the large bowel more difficult. More than 50% of patients with a colonic reservoir have some degree of measurable hyperchloremic metabolic acidosis. The problem is the ammonium chloride resorption and resultant hyperchloremic metabolic acidosis. The intensive mucus production predispose to a higher potential for infection and stone formation. A higher potential for bladder rupture in patients with sigmoid augmentation has been noted (13).

There is some evidence that the absorptive properties of the intestinal segment used for augmentation may decrease with time (14). Certainly histological changes in the intestinal mucosa occur, including mucosal atrophy and decreased villous height. Primary treatment of metabolic acidosis should be alkalization with oral sodium bicarbonate.

Continent colon urinary diversion carries an increased risk of hypokalemia compared to ileal neobladder (15). Severe depletion may result in flaccid paralysis. Treatment for hypokalemia is replacement of potassium in addition to correcting acidosis with bicarbonate.

Although hypocalcaemia and hypomagnesaemia can occur with urinary diversion, they are uncommon. Chronic metabolic acidosis results in the loss of calcium stores from bone as phosphates and sulphates are used to buffer the acids. Clinically significant hypocalcaemia can result in symptoms, including tetany, tremors, irritability and in extremely severe cases death. Treatment is based on calcium repletion. Symptoms of hypomagnesaemia are similar to those that occur with low calcium levels and treatment consists of exogenous replacement.

Augmentation using urothelial segment

Ureterocystoplasty

The main disadvantage of ureterocystoplasty is that it is applicable only in a minority of patients. Ureterocystoplasty has been reported to be effective in some patients with dilated ureter associated with posterior urethral valves, or with a duplex system in which either the upper or lower pole is non-functioning. The distal or entire ureter can be opened to form a flap for bladder augmentation (16). The end result will be a bladder diverticulum which improves bladder compliance. However, the ureteric segment may have significant scaring and will provide an adynamic patch. No metabolic consequences are associated with use of ureter.

Auto-augmentation

Bladder myomectomy to achieve bladder expansion, called auto-augmentation, was firs reported by Cartwright and Snow (17). The principle of surgery is to resect a part of bladder muscle with preservation of bladder mucosa. The resultant bladder diverticulum might give a significant improvement in compliance and capacity, but in some cases a scar formation can occur. Achievement of better compliance after auto-augmentation procedures seems to be less pronounced and of shorter duration than that of conventional enterocystoplasty. On the other hand, the low morbidity and lack of side effects of bowel integration into the urinary tract are the definite advantages of this technique. A possible solution to the problem might be the replacement of bladder muscle with a seromuscular flap (intestine or stomach). The stripping of the mucosa from the intestine, which is a technically demanding procedure. seems to be the key factor for success in this procedure, as retained intestinal mucosa would negate any advantage (18).

Bowel dysfunction, vitamin B12 deficiency and steatorrhea

Bowel dysfunction is known to occur occasionally after enterocystoplasty. Diarrhoea can develop after resection of large segments of ileum, removel of the ileocecal valve , and extensive colonic resections.

Therefore, approximately 15 cm of ileum proximal to the ileocoecal junction should be spared using ileum for augmentation. Vitamin B12 (cyanocobalamin) deficiency is a well recognized abnormality that may arise with resection of the terminal ileum.

Deficiency causes megaloblastic anemia and varying neurological consequences, including peripheral neuropathies, optic atrophy, degenerative changes in the spinal cord involving the dorsolateral columns and dementia.

Surgical resection of the terminal ileum can also result in fat malabsorption, altered bile salt reabsorption and resultant decreased fat-soluble vitamin absorption.

Bone disease: rickets and osteomalacia

Chronic acidosis can result in bone demineralization after enterocystoplasty, resulting in rickets in children and osteomalacia in adults. In response to chronic acidosis bone releases carbonate and phosphate into circulation to buffer excess hydrogen ions. Skeletal calcium content is decreased (19). Because the acid-base changes in patients with enterocystoplasty are often subtle with only slightly decreased calcium, magnesium and bicarbonate, the extent of the impact on bone mineralization is often difficult to assess. In patients who present with rickets or osteomalacia initial treatment should be aimed at the correction of acidosis (20).

Growth retardation

One of the most concerning areas of the use of bowel in the urinary tract in children has been the potential impact on growth. Mingin et al reviewed the literature to critically examined linear growth in children who have had bladder augmentation with a particular emphasis on the correlation between acid-base status, bone mineralization and growth (21). The majority of studies suggest that linear growth is not affected by bladder augmentation. In the short-term, children post-augmentation have varying degrees of metabolic acidosis which, overtime, appears to resolve with no affect on linear growth. No alterations in bone density levels were seen with short-term follow-up. Data with long-term follow-up suggesting that urinary intestinal diversion may negatively impact growth and development. However, these older studies were largely in patients with myelodysplasia and while such patients have growth retardation, it is unclear if that growth retardation was the result of primary disease or urinary diversion.

Surgical complications

Bladder augmentation has revolutionized the care of children with a neuropathic bladder but it remains a major surgical procedure. Metcalfe et al retrospectively reviewed the records of the first 500 bladder augmentations performed from 1978 to 2003 at their institution (22). Charts were reviewed for complications requiring additional surgery, including malignancy, bladder perforation, repeat augmentation, bowel obstruction and bladder calculi. Mean and median follow-up was 13.3 years. Complications occurred in 169 patients (34%) resulting in a total of 254 surgeries. Three patients (0.6%) had transitional cell carcinoma, of whom all presented with metastatic disease and died. Bladder perforation occurred in 43 patients (8.6%) with a total of 53 events. Of the patients 16 (3.2%) required laparotomy for bowel obstruction and 47 (9.4%) required repeat augmentation. Bladder stones were treated in 75 patients (15%), who required a total of 125 surgeries.

Mucus production, infection and stone formation

Mucus production and bladder stone formation both complications related to the use of the gastrointestinal tract for urinary reconstruction. All segments of bowel produce mucus. However, mucus production from the ileum is less than from the colon. Clinically mucus production appears to decrease over time following ileocystoplasty. This is probably because of villous atrophy that occurs in the ileum. Colonic epithelium does not appear to undergo this type of change. Significant mucus production in colonic augmentations continues throughout the life of the patient.

Bacteriuria and colonization of the urinary tract following urinary diversion or augmentation with bowel is common. Several studies show that patients with continent urinary diversion are at increased risk for upper and lower urinary tract calculous disease (23). Calculous rates have been reported to be between 18% and 30%. Several factors may be contributory: urinary stasis, mucous production from the intestinal segment and frequent colonization. Acidosis can also result in the increased mobilization of calcium from bone stores and impaired reabsorption in the distal renal tubule, causing hypercalciuria (24).

The management of calculous disease in urinary diversion and augmentation cases is largely preventive. Patients should receive postoperative instructions to remain hydrated and undergo routine catheterization to prevent urinary stasis. Excess mucus production should be managed by regular irrigation. Recently Hensle et al reported that the use of a standard prophylactic irrigation protocol significantly decreased the rate of reservoir calculous formation from 43% to 7% in patients undergoing augmentation cystoplasty or continent urinary diversion (25).

Malignant transformation

The risk of carcinogenesis in isolated intestinal segment following urinary diversion with a lack of faeces and urine mixture is not well defined. To date there have been 56 such tumours reported, including 31 involving ileal segments and 25 in colonic segments (26). Most tumours reported were adenomas or adenocarcinomas, although transitional cell carcinoma, carcinoid and sarcoma have also been described. Recently a group from Indiana University reported on 3 patients treated with augmentation cystoplasty who subsequently has transitional cell carcinoma (27). The interval between augmentation and cancer diagnosis was 21, 17 and 20 years, respectively. All patients died of metastatic disease. This report highlights the need for long-term follow-up in patients with enterocystoplasty and raises the question of considering routine surveillance cystoscopy in this population (28).

Spontaneous bladder perforation

Spontaneous bladder perforation is a potentially life-threatening complication of augmentation cystoplasty with a reported incidence of up to 13%. A retrospective review of medical records from 1988 to 2001 identified 107 children (57 males and 50 females) who underwent augmentation cystoplasty at Cincinnati Children’s Hospital Medical Centre (29). The overall incidence of bladder perforation was 5%, with one traumatic (1%) and four spontaneous (4%) perforations. All patients recovered uneventfully after exploratory laparotomy.

Patients presented with abdominal pain, distension and occasionally fever, need for prompt diagnosis and treatment. To our knowledge the cause of spontaneous perforation is unknown, although several aetiologies have been suggested. Traumatic catheterization, bladder outlet obstruction and urinary retention, chronic infection and chronic bowel wall ischemia secondary to chronic over distension are possible mechanisms. There is a significant association between a decreased risk of perforation and the use of a strict, incremental catheterization schedule.

Own investigations

In the second part of the paper we would like to briefly introduce the research which has been done in our institute to investigate some metabolic, histological and urodynamic aspects of augmentation in those children who underwent bladder augmentation or substitution (80 patients) over the last 18 years (1988-2006).

Metabolic findings after colocystoplasty in children (30)

This study investigated whether colocystoplasty has resulted in metabolic changes in the growing child during long-term follow-up according to wich part was used: ascending coecum or sigmoid colon.

In order to answer this question twenty-eight patients (mean age at surgery 11 years) were included in the study and divided into two groups: group 1, cystoplasty with coecum and ascending colon (12 patients) and group 2, sigmoid cystoplasty (16 patients). Patients’ linear growth, body mass index, and the following parameters were estimated before surgery and at 3, 6, and 12 months, and then yearly after surgery: blood and urine electrolytes (sodium, potassium, chloride, calcium, phosphorus, magnesium), creatinine, urea, blood gases, blood pH, urine pH, and blood alkaline phosphatase (ALP). All the data were statistically analyzed.

We found that in group 1, the blood ALP increased significantly (P = 0.026) during follow-up. Severe metabolic acidosis with or without hyperchloremia was found in 7 patients. In group 2, the serum sodium and serum calcium levels decreased significantly (P = 0.014 and P = 0.003, respectively); however, the blood ALP, urine sodium, and urine phosphorus levels increased significantly (P = 0.033, P = 0.027, and P = 0.026, respectively) during follow-up. A statistically significant decrease in blood pH (P = 0.022) was found after surgery. Severe metabolic acidosis with or without hyperchloremia was detected in 5 patients. The average linear growth decreased significantly (P = 0.00 1 and P = 0.0 16, respectively) 1 and 2 years postoperatively.

We concluded that the statistically significant increase in blood ALP and decrease in serum calcium indicate bone demineralization after colocystoplasty. Our investigations in children suggest that bone demineralization is more frequent after sigmoid cystoplasty than after the use of coecum and ascending colon.

Histological findings after colocystoplasty and gastrocystoplasty (28)

In this study we conducted a prospective, long-term assessment of the histological changes that can occur following bladder augmentation with colon or stomach.

In order to approach this problem histological evaluations of biopsies from 44 consecutive patients undergoing augmentation (colocystoplasty in 26, gastrocystoplasty in 18) were performed. Patients underwent endoscopic assessment and tissue sampling at 2 or 4-year intervals following the initial augmentation procedure. Patients with less than 2 years of follow-up were excluded from the analysis. Specimens were taken from the native bladder, the augment segment (large bowel or stomach) and the anastomotic line. Sections (4 micron) were examined using standard histological staining methods (hematoxylin and eosin and periodic acid-Schiff) and immunohistochemistry was performed for different markers of neoplasia, cellular proliferation and blood group antigens. Histological findings were correlated with the incidence of stone formation and urinary tract infection.

Group 1 consisted of 20 patients undergoing colocystoplasty who met the criteria for study inclusion. Of the patients 10 (50%) had stones, 19 (95%) had a positive urine culture and 6 had no histological changes. While no cases of malignancy were identified, other forms of pathological change were noted in 14 of the 20 patients (70%). Group 2 included 15 patients undergoing gastrocystoplasty who met the criteria for study inclusion. No stones or malignancy were identified in this group. Positive urine cultures were recorded in 2 patients (13%), no histological changes were found in 6 and 9 (60%) had pathological changes.

We concluded that periodic prospective biopsy evaluation of children who have undergone either colocystoplasty or gastrocystoplasty failed to reveal any histological evidence of malignancy after 10 year follow-up. However, histological evidence of a premalignant lesion 13 years after follow-up suggests that screening for premalignant lesions should be initiated no later than 6 to 10 years following enterocystoplasty.

Therapeutic method for failed bladder augmentation in children: re-augmentation (31)

In collaboration with Turkish paediatric surgeons we looked for a therapeutic method for failed bladder augmentation.

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.

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 follow-up of 6.8 (2-10) years.

Our opinion is that 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.

Does the type of bladder augmentation influence the resolution of pre-existing vesicoureteral reflux? Urodynamic studies (32)

In the literature there are only scanty data how to deal with a pre-existing reflux if bladder augmentation is necessary. The other important topic – not investigated yet – is whether the type of bladder augmentation will influence the resolution of reflux?

The type of bladder augmentation on pre-existing vesicoureteral reflux (VUR) was assessed. The effects of urodynamic changes on the resolution of VUR following augmentation cystoplasty performed with various gastrointestinal segments were examined. It was queried whether elimination of high-pressure bladder is sufficient to resolve pre-existing reflux.

A retrospective record review of patients who underwent bladder augmentation between 1987 and 2004 was done. Patients were divided into two groups. Group I included patients who had a simultaneous augmentation and ureteral reimplantation. Group II included patients with reflux in whom only a bladder augmentation was performed. Pre-and post-augmentation urodynamic results were compared in both groups. The outcome of VUR and the role of various gastrointestinal (GI) segments on the resolution of VUR were studied.

Sixty-three patients underwent bladder augmentation during the study period. Twenty-six of them had VUR before augmentation. There were 10 patients in Group I and 16 patients in Group II. In Group I, VUR ceased in all patients, while in group II, VUR resolved in 14 patients and persisted in two patients. Small and large bowel segments used for augmentation had no effect on the resolution of VUR but the results of gastrocystoplasties were less favourable. Urodynamically there was no significant difference between the various augmentation cystoplasties. Our conclusion is that bladder augmentation alone without simultaneous antireflux repair is usually sufficient for the resolution of pre-existing reflux. The various GI segments used for augmentation have no effect on urodynamic results and the resolution of VUR.

Seromuscular gastrocystoplasty in dogs (33)

Some complex and complicated aspects of bladder augmentation can not be investigated in human material. In these cases we used animal model to approach the problem.

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).

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 was 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.

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.

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 neobladder than when using full-thickness gastrocystoplasty.

Histological findings after gastrocystoplasty in rabbits (34)

Malignant transformation in the augmented bladder is frequently mentioned, only single cases are reported, however, the potential carcinogenesis is hardly investigated in animal model.

We investigated the long-term histological changes after bladder augmentation with gastric segment in an animal subject.

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 tumour protein p53 in the epithelium.

On the native bladder, at the 3-month follow-up, polyps, mucosal oedema, 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. Our investigations supported 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.

Conclusions

Augmenting the bladder is a widely used method in children with developmental abnormalities and it has become a standard part of armamentarium for management of neurogenic and myogenic bladder over the last few decades. However, augmentation is often associated with metabolic consequences and surgical complications. Therefore, besides the improvement of the present complex therapeutic management, the future goal in treating children with abnormal bladders is not catheterization and/or augmentation, but reach normal voiding by avoiding incorporation of gastrointestinal segment in the genitourinary tract and intermittent catheterisation.

 

 

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