Thomas Davidsson

ICUD-EAU International Consultation on Bladder Cancer 2012: Urinary diversion.

CONTEXT A summary of the 2nd International Consultation on Bladder Cancer recommendations on the reconstructive options after radical cystectomy (RC), their outcomes, and their complications. OBJECTIVE To review the literature regarding indications, surgical details, postoperative care, complications, functional outcomes, as well as quality-of-life measures of patients with different forms of urinary diversion (UD). EVIDENCE ACQUISITION An English-language literature review of data published between 1970 and 2012 on patients with UD following RC for bladder cancer was undertaken. No randomized controlled studies comparing conduit diversion with neobladder or continent cutaneous diversion have been performed. Consequently, almost all studies used in this report are of level 3 evidence. Therefore, the recommendations given here are grade C only, meaning expert opinion delivered without a formal analysis. EVIDENCE SYNTHESIS Indications and patient selection criteria have significantly changed over the past 2 decades. Renal function impairment is primarily caused by obstruction. Complications such as stone formation, urine outflow, and obstruction at any level must be recognized early and treated. In patients with orthotopic bladder substitution, daytime and nocturnal continence is achieved in 85-90% and 60-80%, respectively. Continence is inferior in elderly patients with orthotopic reconstruction. Urinary retention remains significant in female patients, ranging from 7% to 50%. CONCLUSIONS RC and subsequent UD have been assessed as the most difficult surgical procedure in urology. Significant disparity on how the surgical complications were reported makes it impossible to compare postoperative morbidity results. Complications rates overall following RC and UD are significant, and when strict reporting criteria are incorporated, they are much higher than previously published. Fortunately, most complications are minor (Clavien grade 1 or 2). Complications can occur up to 20 yr after surgery, emphasizing the need for lifelong monitoring. Evidence suggests an association between surgical volume and outcome in RC; the challenge of optimum care for elderly patients with comorbidities is best mastered at high-volume hospitals by high-volume surgeons. Preoperative patient information, patient selection, surgical techniques, and careful postoperative follow-up are the cornerstones to achieve good long-term results.

Should All Patients with Non–Muscle-Invasive Bladder Cancer Receive Early Intravesical Chemotherapy after Transurethral Resection? The Results of a Prospective Randomised Multicentre Study

BACKGROUND To decrease recurrences in non-muscle-invasive bladder cancer (NMIBC), the European Association of Urology (EAU) guidelines recommend immediate, intravesical chemotherapy after transurethral resection (TUR) for all patients with Ta/T1 tumours. OBJECTIVE To study the benefits of a single, early, intravesical instillation of epirubicin after TUR in patients with low- to intermediate-risk NMIBC. DESIGN, SETTING, AND PARTICIPANTS In this prospective randomised multicentre trial, 305 patients with primary as well as recurrent low- to intermediate-risk (Ta/T1, G1/G2) tumours were enrolled between 1997 and 2004. Patients were randomly allocated to receive 80 mg of epirubicin in 50 ml of saline intravesically within 24 h of TUR or no further treatment after TUR. MEASUREMENTS The primary end point was time to first recurrence. RESULTS AND LIMITATIONS A total of 219 patients remained for analysis after exclusions. The median follow-up time was 3.9 yr. During the study period, 62% (63 of 102) of the patients in the epirubicin group and 77% (90 of 117) in the control group experienced recurrence (p=0.016). In a multivariate model, the hazard ratio (HR) for recurrence was 0.56 (p=0.002) for early instillation of epirubicin versus no treatment. In a subgroup analysis, the treatment had a profound recurrence-reducing effect on patients with primary, solitary tumours, whereas it provided no benefits in patients with recurrent or multiple tumours. Furthermore, patients with a modified European Organisation for Research and Treatment of Cancer (EORTC) risk score of 0-2 with and without single instillation had recurrence rates of 41% and 69%, respectively (p=0.003), whereas the corresponding rates for those with a risk score of > or = 3 were 81% and 85%, respectively (p=0.35). CONCLUSIONS A single, early instillation of epirubicin after TUR for NMIBC reduces the likelihood of tumour recurrence; however, the benefit seems to be minimal in patients at intermediate or high risk of recurrence. Future trials will determine the value of early instillation in addition to serial instillations in NMIBC.

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.

Transurethral Resection of Non–Muscle-Invasive Bladder Transitional Cell Cancers With or Without 5-Aminolevulinic Acid Under Visible and Fluorescent Light: Results of a Prospective, Randomised, Multicentre Study

BACKGROUND Fluorescent light (FL)-guided cystoscopy induced by 5-aminolevulinic acid (5-ALA) has been reported to detect more tumours compared with standard white-light (WL) cystoscopy. Most reports are from single centres with relatively few patients. OBJECTIVE To evaluate whether 5-ALA-induced FL and WL cystoscopy at transurethral resection (TUR) is superior compared with standard procedures under WL only with respect to tumour recurrence and progression in patients with non-muscle-invasive bladder cancer. DESIGN, SETTING, AND PARTICIPANTS This randomised, multicentre, observer- and pathologist-blinded, prospective phase 3 clinical trial enrolled 300 patients, and of those patients, 153 were randomised to FL cystoscopy and 147 were randomised to standard WL cystoscopy. INTERVENTION All patients were first inspected under WL and all lesions were recorded. Patients randomised to FL underwent a second inspection. TUR was carried out in both groups. MEASUREMENTS Control cystoscopy under WL was performed in all patients every 3 mo during the first year after randomisation and biannually thereafter. RESULTS AND LIMITATIONS At the first TUR, the mean number of resection specimens per patient was 2.5 (FL: 2.5; WL: 2.4; p=0.37) and the resulting mean number of resected tumours was 1.7 with FL and 1.8 with WL (p=0.85). More patients were diagnosed with carcinoma in situ (CIS) in the WL group (13%) than in the FL group (4.2%). Within-patient comparison of FL patients only showed that FL detected more lesions than WL. Tumour lesions solely detected by FL cystoscopy that would not otherwise be detected by WL cystoscopy included 52% dysplasia, 33% CIS, 18% papillary neoplasms, 13% pT1, and 7% pTa. Outcome at 12 mo did not show any difference between groups with regard to recurrence-free and progression-free survival rates. CONCLUSIONS In this prospective, randomised, multi-institutional study, we found no clinical advantage of FL cystoscopy compared with WL cystoscopy and TUR.

Intraoperative sentinel node detection improves nodal staging in invasive bladder cancer.

PURPOSE We evaluated intraoperative SN detection in patients with invasive bladder cancer during radical cystectomy in conjunction with extended lymphadenectomy. MATERIALS AND METHODS A total of 75 patients with invasive bladder cancer underwent radical cystectomy with extended lymphadenectomy. SNs were identified by preoperative lymphoscintigraphy, intraoperative dynamic lymphoscintigraphy and blue dye detection. An isotope (70 MBq (99m)Tc-nanocolloid) and Patent Blue(R) blue dye were injected peritumorally via a cystoscope. Excised lymph nodes were examined ex vivo using a handheld gamma probe. Identified SNs were evaluated by extended serial sectioning, hematoxylin and eosin staining, and immunohistochemistry. RESULTS At lymphadenectomy an average of 40 nodes (range 8 to 67) were removed. Of 75 patients 32 (43%) were lymph node positive, of whom 13 (41%) had all lymph node metastases located only outside of the obturator spaces. An SN was identified in 65 of 75 patients (87%). In 7 patients an SN was recognized when the nodal basins were assessed with the gamma probe after lymphadenectomy and cystectomy. Of the 32 lymph node positive cases 26 (81%) had a positive (metastatic) SN. Thus, the false-negative rate was 6 of 32 cases (19%). Five false-negative cases had macrometastases and/or perivesical metastases. In 9 patients (14%) the SN contained micrometastases (less than 2 mm), in 5 of whom the micrometastasis was the only metastatic deposit. CONCLUSIONS SN detection is feasible in invasive bladder cancer, although the false- negative rate was 19% in this study. Extended serial sectioning and immunohistochemistry revealed micrometastases in SNs in 9 patients and radio guided surgery after the completion of lymphadenectomy identified SNs in an additional 7. We believe that the technique that we used in this study improved nodal staging in these 16 of 65 patients (25%).

Continent urinary tract reconstruction – the Lund experience

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.

Long-term metabolic effects of urinary diversion on skeletal bone: histomorphometric and mineralogic analysis.

OBJECTIVES To evaluate the long-term influence of different types of intestinal urinary diversion on skeletal bone and its mineral content. METHODS Densitometry was used to estimate bone mineral content, and bone biopsies were analyzed with histomorphometric technique. The study comprised 20 patients with conduit urinary diversion and 19 with cecal continent reservoir, all followed up for more than 5 years, with normal or near-normal renal function. RESULTS Bone mineral content did not differ significantly between the patients with cecal continent urinary reservoir and those with conduit diversion or between these groups and a reference group. At the cellular level, the histomorphometric analysis revealed no defective bone mineralization or increased bone resorption in either group of patients. The trabecular bone volume was greater than normal in the reservoir group, but not in the conduit group. The appositional rate was significantly below normal in both groups of patients, but did not differ between conduit and reservoir patients. CONCLUSIONS Subtle changes in electrolytes and acid-base homeostasis identified in adults with intestinal segments incorporated in the urinary tract and with largely normal renal function do not seem to influence bone mineralization in the long term. At the cellular level, a lower than normal appositional rate was found in the patients with conduit or continent urinary diversion. In the latter group, this finding, together with increased trabecular bone volume, may indicate a decrease of bone turnover.

The Detubularized Right Colonic Segment as Urinary Reservoir: Evolution of Technique for Continent Diversion

Continent diversion of urine via a cecal-right colonic reservoir has been performed at our university hospital since 1977. Several modifications of surgical technique have been devised to prevent problems of urinary leakage and difficulties in catheterization. The current technique, used during the last 3 years on 14 patients, involves use of a detubularized right colonic segment as a reservoir, ileal mesenteric exclusion, fashioning the intussuscepted ileal nipple valve with staples and anchoring of a fascia strip sling around the nipple base to the anterior rectus sheath. Complication from the reservoir outlet occurred in only 1 patient.

Cystourethrometric findings in patients with detubularized right colonic segment for bladder replacement.

Urodynamic evaluation was performed in 13 men 4 to 18 months after cystoprostatectomy and bladder replacement using a detubularized right colonic segment. All patients are continent by day and only 3 are incontinent during the night to a degree that necessitates use of a condom catheter. Two patients awaken every 2 to 3 hours to void and the remainder have nocturia comparable to normal men of their age. The residual volume was 0 to 70 ml. The urethral closure pressure was normal, and in 3 patients studied preoperatively and postoperatively no significant change was observed other than shortening of the profile length. Maximal flow rates were normal although the pattern was intermittent. In 2 patients no cystoplasty contractions were recorded and in all but 2 patients the amplitude of the contractions was less than 40 cm. water. Simultaneous bladder and urethral pressure recordings during bladder filling demonstrated no change in urethral pressure in 10 patients. Although creation of a reservoir with a low pressure and careful preservation of the infraprostatic urethra are important for continence in these patients, we believe that the absence of normal sacral route reflexes after cystoprostatectomy is an important contributing cause to nocturnal incontinence.

The nested variant of urothelial carcinoma: a rare but important bladder neoplasm with aggressive behavior Three case reports and a review of the literature

OBJECTIVE To describe our experience with the nested variant of urothelial carcinoma (UC-NV) of the bladder, by characterization of the clinical picture and the prognostic implications of this rare form of bladder neoplasm. MATERIALS AND METHODS Three cases of UC-NV of the bladder treated in our institutions were revised and data compared with previously published case-reports. RESULTS Three patients presented with advanced muscle-invasive UC-NV, of which two had lymph node metastasis at cystoprostatectomy. The histopathology in the latter two cases showed the same picture in the lymph node metastasis as in the primary tumor with nests of tumor cells with mild-moderate atypia. In all three cases the tumor involved a ureteric orifice or the bladder neck. CONCLUSION UC-NV is a rare but important histopathologic entity. It has a poor prognosis. At early stage, tumors might be difficult to differentiate from benign conditions and awareness of the condition is of outermost importance.