[Patients' acceptance of urinary diversion. The pouch of Sisyphus]. / Aspekte der Akzeptanz von Harnableitung: Der Pouch des Sisyphos.

It is important that any patient with a urinary diversion can accept the psychological impact alongside the surgical and physical aspects. However, there are currently no validated methods or instruments available to allow direct measurement of this phenomenon in these patients. Health-related quality of life (HRQoL) is often high following different types of urinary diversion-this may suggest a high acceptance level and thus may act as a secondary end point. Such an assessment is a retrospective validation of successful patient selection, allowing us to redirect the nihilistic misinterpretation that urologists should return to offering ileal conduits as a standard. In modern urinary diversion, high patient acceptance develops from comprehensive counselling providing a realistic expectation, careful patient-to-method-matching, strict adherence to surgical detail during the procedure and a meticulous lifelong follow-up. Coping strategies, disease-related social support and confidence in the success of treatment are among other factors which contribute to acceptance of urinary reconstruction as either independent or combined factors. Significant experience is required in every respect, as misjudgement and mistakes in any of these issues may be detrimental to the patients' health. It should be acknowledged that there is no 'best' urinary diversion in general terms. A reconstructive surgeon must have all techniques available and choices need to be tailored to the individual patient.

Molecular characterization of early-stage bladder carcinomas by expression profiles, FGFR3 mutation status, and loss of 9q.

We used gene expression profiling, mutation analyses of FGFR3 and TP53, and LOH analyses of chromosome 9 and the TP53 region on chromosome arm 17p, to molecularly characterize 75 Ta and T1 bladder carcinomas. We identified four major cellular processes related to cell cycle, protein synthesis, immune response, and extra cellular components that contribute to the expressional heterogeneity of early-stage urothelial cell carcinoma (UCC). Activating FGFR3 mutations were found at the highest frequency in G1 tumors (80%), and showed a strong correlation with FGFR3 expression. In contrast, G3 tumors displayed mutations in less than 10% of the cases and a low level of FGFR3 expression. Even though LOH on chromosome 9 was not associated with any specific expression pattern, our data indicate that loss of chromosome 9 is associated with tumor development rather than initiation. The combined analyses suggest the existence of two types of UCC tumors, one which is characterized by FGFR3 mutation or expression, high expression of protein synthesis genes, and low expression of cell cycle genes. Furthermore, the presented data underscore FGFR3 receptor involvement in urothelial cell transformation as the presence of FGFR3 mutations has a major impact on the global gene expression profile of bladder carcinomas.

Neutral third party versus treating institution for evaluating quality of life after radical cystectomy.

OBJECTIVE: To evaluate the possible impact of a neutral third party on the patients' responses to health-related quality of life (HRQL) instruments. METHODS: 119 patients operated at the Department of Urology in Lund with radical cystectomy and continent urinary tract reconstruction (continent cutaneous diversion or orthotopic bladder substitution) for locally advanced bladder cancer were included in the study. They were randomly divided in two groups, similar with regard to gender, age, length of follow-up, and type of reconstruction. The EORTC instruments QLQ-C30 and QLQ-BLM30 were sent to the patients. One group; "Lund patients", received the instruments from the Department of Urology in Lund, while the other group; "Stockholm patients", received the instruments from a neutral third party, i.e. "The Project Health and Well-Being" at the Karolinska Institutet in Stockholm. RESULTS: Response rates were high in both groups, 59 out of 60 among Lund patients and 57 out of 59 among Stockholm patients. There were statistically significantly more bowel problems reported in the Stockholm patients than in the Lund patients (p<0.05) in the QLQ-C30 instrument. Regarding type of reconstruction, the Stockholm patients with continent cutaneous diversion scored higher for constipation than the Lund patients (p<0.05), and the Stockholm patients with bladder substitution scored lower for emotional functioning and higher for dyspnoea and economical problems than the Lund patients (p<0.05. There were no statistically significant differences between the Lund patients and the Stockholm patients in the QLQ-BLM30 instrument. CONCLUSION: Though few factors differed between the two groups, the results may indicate that different results are obtained when a study is totally administered and analyzed by a neutral third party as compared with the surgeon or his or her institution. Larger studies are needed to further test this hypothesis.

[Transitional cell carcinoma of the prostate in cystoprostatectomy specimens]. / Transitional cell carcinoma der Prostata im Zystoprostatektomiepräparat.

PURPOSE: Transitional cell carcinoma (TCC) of the prostate/prostatic urethra is a risk factor for urethral recurrence after radical cystoprostatectomy for TCC. Using conventional sectioning techniques, prostate involvement (prostatic urethra, acini, ducts and/or stroma) has been detected in a range of 10-20% of the patients, whereas transversal whole mount sectioning has revealed 43 % prostate involvement in two reported series. Due to different mechanisms of prostate involvement (intraurethral, extravesical and direct overgrowth into the prostatic stroma), preoperative transurethral biopsies of the prostate might not accurately determine such involvement. In this study we examine the prostate using a longitudinal whole mount sectioning technique, correlate TCC of the prostate with the characteristics of the bladder tumour and, thus, validate the preoperative transurethral resection biopsies. MATERIAL AND METHODS: Patients scheduled for cystoprostatectomy or cystoprostatourethrectomy were investigated by preoperative resection biopsies from the prostatic urethra and mapping of the bladder. The cystectomy specimen was fixated with the bladder filled with formalin, and the prostate and bladder neck examined using longitudinal whole mount sectioning. RESULTS: In 13 of the 43 (30%), patients TCC was identified in the prostate. Of these 13 patients, 9 had been identified in the preoperative resection biopsies from the prostatic urethra. Of the patients with prostatic involvement, 46% had carcinoma in situ (Cis) in the bladder neck/trigone and 38% had multifocal Cis in the bladder. Comparing this to the group of patients without prostatic involvement, the respectively figures are 20% and 23%. A tumour in the trigone, either invasive or Cis, was detected in 5/13 patients with prostatic involvement as compared to one patient (3%) without TCC of the prostate. Multiple bladder tumours were more common in patients with prostatic involvement and were larger (3.2 cm compared to 2.2 cm). CONCLUSIONS: Preoperative resection biopsies from the prostatic urethra do not always detect TCC in the prostate. Cis in the bladder neck/trigone or multifocal and multiple bladder tumours could be risk factors for prostate involvement of TCC.

[Bladder cancer and the sentinel node concept]. / Sentinel-Node-Diagnostik beim invasiven Blasenkarzinom.

PURPOSE: Lymph node status is one of the most important prognostic factors in muscle-invasive bladder cancer. The extent of lymphadenectomy performed in conjunction with cystectomy and the question as to whether this is a staging or therapeutic intervention are matters of discussion. The aim of this study was to evaluate the sentinel node (SN) concept and to correlate findings with tumour status in excised regional lymph nodes. MATERIAL AND METHOD: 26 patients scheduled for cystectomy were investigated with preoperative lymphoscintigraphy, peroperative dye detection (Patent Blue) and dynamic lymphoscintigraphy (Nanocoll or Albures 50 MBq/ml). The substances were injected adjacent to the tumour in the detrusor muscle. RESULTS: Sentinel nodes were detected in 21 of the 26 of the investigated patients. 7/21 SN were located outside the obturator fossa. Of the eight patients with lymph node metastasis, five displayed metastasis in lymph nodes outside the obturator fossa. There was one false negative SN in a patient with multifocal tumour, while in the other seven patients with lymph node metastasis, these were detected in the SN. CONCLUSION: Sentinel node detection is possible in most cases of bladder cancer scheduled for cystectomy. The significance of utilizing this method to detect lymph node metastasis outside the obturator fossa warrants further investigation.

Continent urinary tract reconstruction - the Lund experience.

UNLABELLED: The Department of Urology in Lund, Sweden, has a long association with innovations in reconstructive urology. The authors from that department describe their experience over a long period with orthotopic bladder substitution and continent cutaneous urinary diversion. They conclude that continent urinary tract reconstruction is associated with a high incidence of early and late complications. They also found that for storage and emptying, their Lundiana pouch was superior to the Goldwasser neobladder. OBJECTIVE: To assess the early and late complications and functional results in patients undergoing continent reconstruction of the urinary tract, i.e. orthotopic bladder substitution (OBS) or continent cutaneous diversion (CCD). PATIENTS AND METHODS: The medical records of all patients undergoing OBS (Goldwasser technique) or CCD ('Lundiana' technique) for malignant or benign disease during 1987-1999 and followed to December 2001 were reviewed. There were 67 patients with neobladders, 77 with a Lundiana pouch who had undergone radical cystectomy and 22 with a Lundiana pouch operated for benign disorders. RESULTS: Early complications requiring reoperation occurred in 12% of the cystectomy group, with no difference with type of reconstruction, and in 10% with benign diseases. Four patients (3%) undergoing radical cystectomy died from early cardiovascular complications, two after surgery for intra-abdominal complications. Intestinally related complications and wound dehiscence requiring re-operation occurred in nine and six patients, respectively. The incidence of late complications requiring open surgery was 22% and 23% after cystectomy with OBS and CCD, respectively. The value in patients with benign diseases undergoing CCD was also 23%. Stone formation in the pouch was common, occurring in 12% in patients with OBS and in 10% after CCD. The pouch perforated or ruptured in four patients. The incidence of uretero-intestinal stricture using the Le Duc technique was 2.4% and renal function was well preserved. The incidence of revisional surgery of the Lundiana pouch outlet for incontinence was low and all patients but four were continent. The functional outcome in patients with OBS was less good; some needed pouch augmentation or an artificial urinary sphincter. Most patients used incontinence products and many needed clean intermittent self-catheterization. CONCLUSION: Continent urinary tract reconstruction is associated with a high incidence of early and late complications. For storage and emptying, the CCD Lundiana pouch is superior to the OBS of Goldwasser.

The quality of life in men after radical cystectomy with a continent cutaneous diversion or orthotopic bladder substitution: is there a difference?

OBJECTIVE: To compare the quality of life (QoL) in men after radical cystectomy who had either a continent cutaneous diversion or orthotopic bladder substitution. PATIENTS AND METHODS: Eighty men with at least 6 months of follow-up and with no signs of recurrent disease after radical cystectomy for bladder carcinoma, and who had either a continent cutaneous diversion or orthotopic bladder substitution, were sent two types of questionnaire, the Functional Assessment of Cancer Therapy-Bladder Cancer (FACT-Bl) and the Hospital Anxiety and Depression Scale (HADS), to determine their QoL. RESULTS: The FACT-Bl and HADS questionnaires were returned by 90% and 71% of the patients, respectively (P < 0.05). In the replies to the generic version of FACT-Bl there were no differences between the groups in any domain, the scores being high in all. In questions covering intestinal, urinary and sexual items, patients with continent diversion had less trouble controlling urine (P < 0.0001), had to empty less often (P < 0.001), and had fewer symptoms when emptying (P < 0.05). Patients with neobladders had a better appreciation of appearance and better preserved erectile function (both P < 0.05). In the answers to the HADS, the mean scores were low (within the normal ranges) and did not differ between the groups. CONCLUSION: Using two instruments tested for validity and reliability, there were no differences between patients with continent diversion and those with orthotopic substitution.

Reconstructive urology in the nordic countries--a hospital questionnaire survey.

A hospital survey of adult reconstructive urologic surgery in the Nordic countries is presented. The response rate was 80% and included most general hospitals and university clinics. Despite similarities between the healthcare systems of the various countries several differences were found. Cystectomy was performed in a large number of institutions in all countries except Denmark. The annual number of orthotopic bladder substitutions per institution was calculated as three to four (range of medians for each country) and the number of continent cutaneous diversions as two to seven. Open urethral procedures were performed more frequently in Sweden than in the other countries. Surgery for penile curvature and implantation of three-component prostheses for erectile dysfunction was more commonly performed in Denmark and Iceland compared to Sweden.

Permeability of intestinal mucosa from urinary reservoirs in man and rat.

OBJECTIVE: To evaluate the barrier properties of intestinal mucosa chronically exposed to urine and to evaluate possible differences between ileal and colonic segments used in the reconstruction of the urinary tract. MATERIALS AND METHODS: Mucosal specimens from patients with continent reservoirs with an abdominal stoma, or orthotopic neobladders constructed from colonic segments, were obtained at revisional surgery. Control segments were obtained during right-sided hemicolectomy. In addition, ileal and colonic segments from enterocystoplasties in rats were assessed. The mucosa-to-serosa passage of marker molecules, i.e. (14)C-mannitol, (3)H-glucose, fluorescein isothiocyanate-dextran 4400 and ovalbumin, was measured using modified Ussing diffusion chambers. RESULTS: In man, there were no permeability differences between segments exposed to urine and control segments for any of the marker molecules. In rats, there was less passage of markers in ileal and colonic transplanted segments than in intestinal segments from sham-operated animals. CONCLUSIONS: Intestinal mucosa that has been in chronic contact with urine maintains its barrier function; in the rat model the permeability was even decreased. In addition, there were no detectable differences between ileal and colonic segments in this model.

Urinary diversion and bladder substitution in patients with bladder cancer.

For the majority of patients with invasive bladder carcinoma, radical cystectomy remains the gold standard of care. As a result the twentieth century has seen the continuous development of methods for reconstructing the urinary tract. Two decades ago the ileal conduit was by far the most commonly used method, whereas today methods geared toward patient continence are first choices in most centers. Some of these methods are unquestionably more complex than the ileal conduit, yet whether they actually yield uniformly improved quality of life is the cause of much debate. Many different variables play a role in determining the best type of reconstruction for an individual bladder cancer patient. This review analyzes the different factors that must be considered to obtain an optimal match between patient and reconstructive method.

Quality of life after radical cystectomy and orthotopic bladder substitution: a comparison between Italian and Swedish men.

OBJECTIVE: To investigate possible differences between Italian and Swedish men in health-related quality of life (HRQL) after cystectomy and orthotopic bladder substitution for bladder cancer. PATIENTS AND METHODS: Thirty-three men in Padua, Italy and 33 in Lund, Sweden were assessed after respective mean postoperative periods of 42 and 52 months. Three questionnaires were used: (i) dealing with view-of-life issues; (ii) the core questionnaire QLQ-C30(+3) from the European Organization for Research and Treatment of Cancer, with added questions on urinary symptoms and sexuality; and (iii) one focusing on postoperative psychosocial and sexual adjustment. RESULTS: While Italian and Swedish men did not differ in their central values, they differed significantly in belief-related values, such as religion. Urinary problems and erectile dysfunction were common in both groups, the former possibly commoner in the Swedish men and the latter in the Italians. Changes in mood and self-esteem were common in both groups. On a visual analogue scale, the Italian men reported a worse present mood than the Swedish men, but expressed a more favourable outlook on their future. CONCLUSION: Despite differences in philosophical attitudes between Italian and Swedish men, there were no major differences in HRQL. Caution is required in interpreting these findings because there were few participants and the possible inadequacy of the methods used to evaluate the complex concept of quality of life.

The effect of isoniazid on BCG-induced toxicity in patients with superficial bladder cancer.

The use of bacillus Calmette-Guérin in the treatment of transitional cell cancer of the bladder has caused concern because of its associated adverse effects. We conducted a randomized prospective, double-blind, multicentre study to determine whether isoniazid prophylaxis could reduce BCG-induced toxicity without compromising its immunotherapeutic effects. Patients (n = 160) with histologically documented urothelial cancer (pTa-T1, pTis, G1-3) were treated with 6 weekly instillations of BCG Connaught strain, 81 mg, administered concomitantly with a 3-day course of isoniazid (300 mg o.d.) or placebo. Side-effects were recorded with each treatment and at follow-up. Of the patients treated with isoniazid, 19% remained free from side-effects, compared with 16% of the placebo group. Local side-effects confined to the bladder were significantly lower among those receiving isoniazid (35% vs. 48%, p < 0.01). Local side-effects together with systemic adverse effects such as fever, nausea or skin rash were experienced by 30% of patients in each arm. There were no differences in tumour recurrence between the two patient groups. Concomitant isoniazid reduces the local, but not the systemic side-effects of topically applied BCG without compromising the antitumour effect on superficial, transitional cell cancer of the bladder during a follow-up period that now exceeds 2 years.

When the bladder is gone: quality of life following different types of urinary diversion.

Methods aiming for continence after radical cystectomy for bladder cancer, e.g., continent cutaneous urinary diversion and orthotopic bladder substitution, have become clinically accepted alternatives to ileal conduit diversion in the past decade. The a priori assumption has been that improvement in the postoperative quality of life would be greater following the new methods than after ileal conduit diversion. Studies on the validity of this assumption have been hampered by a lack of consensus on what should be measured and how this should be done: in no two studies have identical test instruments been used. The frequent inclusion of patients with nonmalignant disease has also impeded comparative evaluation of reports. By and large, published studies do not seem to confirm that the new types of urinary tract reconstruction improve the quality of life of bladder cancer patients. Common for all methods are psychosocial and sexual problems.

Sprouting of bladder nerves into cystoplastic cecal segment in the rat.

Incorporation of bowel into the bladder (enterocystoplasty) has been widely used to increase bladder capacity. It has been reported by others that the response of smooth muscle from the cystoplastic segment of the intestine shifts from that of the intestine (relaxation to alpha-agonists and ATP) to that of the bladder (contraction to alpha-agonists and ATP). This suggests a functional integration of the intestinal muscle into the bladder; the mechanisms are unknown. The aims of the present study were (1) to elucidate if there are signs of bladder nerves sprouting across the anastomosis into the intestinal segment, and (2) to study what happens with the intrinsic innervation of the intestinal segment. As a model, we used cecocystoplasty in rats. The bladder was opened and a patch of cecum with intact vascular supply was anastomosed to the bladder. After two to 11 months the rats were sacrificed and the bladders mounted as wholemounts and stained for acetylcholinesterase-containing nerves, or embedded in paraffin for histology. A pronounced degeneration of the myenteric plexus was found in the cecal segments. In some areas, this had proceeded to the extent that the ganglia were isolated ovoid lumps of cells with no apparent connection to other ganglia. Areas lacking ganglia and nerve trunks but still with muscle could be found in all specimens. Abundant axon bundles were demonstrated sprouting from the cut bladder nerves close to the anastomosis. The bundles spread out in a fan-like pattern or were organized as fewer thicker nerves. There were many nerve bundles entering the cecal segment where they branched and the diameter decreased till they no longer became visible. Some nerves reached surviving lumps of myenteric ganglion cells. The results show that the bladder nerves sprout into the anastomosed cecal segment. It is reasonable to assume that these nerves are responsible for the changes in receptor pharmacological properties of the cecal smooth muscle towards that of bladder muscle.

Urodynamic factors influence the duration of Escherichia coli bacteriuria in deliberately colonized cases.

PURPOSE: We evaluated the influence of urodynamic factors on the establishment of bacteriuria, after deliberate intravesical inoculation with Escherichia coli. MATERIALS AND METHODS: Nine women and 7 men with recurrent symptomatic urinary tract infections underwent intravesical injection of E. coli 83972. This strain had documented ability to persist in the urinary tract and it lacks expressed virulence factors associated with urinary tract infection. RESULTS: Successful long-term colonization (5 months to 3 years) was achieved in 6 of 12 patients with neurogenic bladder disorder, including normal or high bladder capacity, normal or low detrusor pressure and residual urine. Short-term bacteriuria (13 days) occurred in 1 but long-term bacteriuria was not established in the 4 patients with normal lower urinary tract function. Occasionally urine samples from the colonized patients contained other bacterial strains, which cleared spontaneously except for a Klebsiella strain that became established in 2 and subsequently eliminated E. coli 83972. CONCLUSIONS: E. coli 83972 bacteriuria could only be established in a subset of patients with defective bladder voiding, suggesting that urodynamic defects permit a nonvirulent strain to establish in the urinary tract, but that additional host factors determine if bacteriuria will persist.

Reflux, stricture and glomerular filtration rate after two antireflux techniques in continent urinary reconstruction using the right colon.

In the present study the incidence of reflux, stricture formation and changes in glomerular filtration rate in patients with the submucosal tunnel or the Camey-Le Duc technique of ureteric implantation into the caecum/detubularized right colon used for continent cutaneous diversion/orthotopic bladder substitution was investigated. Reflux was found in two renal units and ureterointestinal stenosis occurred in five renal units after submucosal tunnel ureteric implantation. After Camey-Le Duc ureteric implantation, one renal unit showed reflux and none had stenosis of the ureterointestinal anastomosis during follow-up. Mean glomerular filtration rate (ml/min/1.73 m2) fell from 98 to 85 in the submucosal tunnel group and from 88 to 81 in the Camey-Le Duc group after mean follow-ups of 9 and 5 years, respectively. Both methods of ureteric implantation in this study were effective in preventing reflux, and renal function was well preserved in both groups. The absence of ureterointestinal strictures in the Camey-Le Duc group is encouraging and indicates that this is a reliable method for reflux prevention.

Metabolic alterations at different levels of renal function following continent urinary diversion through colonic segments.

PURPOSE: We evaluated the influence of renal function on electrolyte and acid-base homeostasis in patients with colonic reservoirs for urine and the ability of these patients to handle an acute acid load. MATERIALS AND METHODS: The 19 patients studied were divided into 2 groups according to preservation of the glomerular filtration rate at last followup: group 1-well preserved glomerular filtration rate (mean 100 ml. per minute per 1.73 m.2) with an average followup of 8.5 years and group 2-slight to moderate decrease in glomerular filtration rate (mean 55 ml. per minute per 1.73 m.2) with a mean followup of 10.5 years. Renal tubular function was evaluated by urinary levels of protein alpha 1-microglobulin. Baseline serum and urine samples were analyzed for metabolic parameters, and baseline arterial blood gas was measured. Immediately thereafter ammonium chloride loading was performed. RESULTS: Some difference in acid-base homeostasis was found with slight hyperchloremic metabolic acidosis noted in 4 patients in group 2. Moreover, calcium homeostasis was influenced, with lower levels of ionized calcium noted in group 2. However, no difference was found in the ability of the patients in both groups to handle an acute acid challenge. CONCLUSIONS: Patients with a glomerular filtration rate of approximately 55 ml. per minute per 1.73 m.2 have sufficient renal function to compensate for the chronic endogenous acid load noted after urinary diversion and they can also handle an acute acid load adequately. Further studies are necessary to evaluate the long-term effects of a chronic endogenous acid load, for example on bone metabolism, in patients with impaired renal function after urinary intestinal diversion.

Perforation of continent urinary reservoirs. Scandinavian experience.

In a questionnaire survey of urological departments in Sweden, Denmark, Finland and Norway, 20 episodes of perforation of continent urinary pouches were found to have occurred in 18 patients, representing an incidence of 1.5%. This complication occurred with ileal as well as colonic segments, without predilection. In one case there was perforation of an appendiceal outlet. Noticeable findings were (a) a long delay (median 10h) to treatment and (b) that investigational procedures such as enterocystography and enterocystoscopy were not commonly employed. Treatment of this potentially lethal complication was by oversewing the perforation, and there were no subsequent major complications. This complication should be strongly suspected if a patient with continent urinary reconstruction presents with acute abdominal pain.