An Updated Critical Analysis of the Treatment Strategy for Newly Diagnosed High-grade T1 (Previously T1G3) Bladder Cancer

Context

High-grade T1 (formerly T1G3) bladder cancer (BCa) has a high propensity to recur and progress. As a result, decisions pertaining to its treatment are difficult. Treatment with bacillus Calmette-Guérin (BCG) risks progression and metastases but may preserve the bladder. Cystectomy may offer the best opportunity for cure but is associated with morbidity and a risk of mortality, and it may constitute potential overtreatment for many cases of T1G3 tumours. For purposes of this review, we continue to refer to high-grade T1 lesions as “T1G3.”

Objective

To review the current literature on the management of T1G3 BCa and to provide recommendations for its treatment.

Evidence acquisition

A National Center for Biotechnology Information (NCBI) PubMed search for relevant articles published between 1996 and 9 January 2009 was performed using the Medical Subject Headings “T1G3” or “T1” and “Bladder cancer.” Articles relevant to the treatment of T1G3 BCa were retained.

Evidence synthesis

The diagnosis of T1G3 disease is difficult because pathologic staging is often unreliable and because of the risk of significant understaging at initial transurethral resection (TUR) of bladder tumour. A secondary restaging TUR is recommended for all cases of T1G3. A single dose of immediate post-TUR chemotherapy is recommended. For a bladder-sparing approach, intravesical BCG should be given as induction with maintenance dosing. Immediate or early radical cystectomy (RC) should be offered to all patients with recurrent or multifocal T1G3 disease, those who are at high risk of progression, and those failing BCG treatment.

Conclusions

Both bladder preservation and RC are appropriate options for T1G3 BCa. Risk stratification of patients based on pathologic features at initial TUR or at recurrence can select those most appropriate for bladder preservation compared to those for whom cystectomy should be strongly considered.     

A Critical Analysis of Orthotopic Bladder Substitutes in Adult Patients with Bladder Cancer: Is There a Perfect Solution?

Context

Orthotopic bladder substitute (OBS) has been popularized over the past 2 decades as a diversion following radical cystectomy for invasive bladder cancer. Various reports, mostly single-center experiences, are published on patients with OBS.

Objective

This study reviews the literature regarding indications, postoperative care, complications, quality-of-life measures, as well as functional and oncologic outcomes that have been published on patients with OBS.

Evidence acquisition

An English-language literature review of the Medline database (1990 to January 2010) of published data on patients with OBS following radical cystectomy for bladder cancer was undertaken. Articles that included surgery for noncancer etiology were excluded.

Evidence synthesis

Indications and patient selection criteria have significantly widened over the past 2 decades. Comparable oncologic data have been reported between patients with OBS versus other diversions. Secondary urethral tumors seem less common in patients with OBS compared with those with conduits or continent cutaneous diversions. Durable daytime and nocturnal continence is achieved in 85–90% and 60–80%, respectively. Continence is inferior in elderly patients with OBS. Urinary retention remains significant in the female patients, ranging from 25% to 50%. Complications including electrolyte disturbances, altered sensorium and drug metabolism, mucus retention, rupture, urinary tract infections, and upper tract deterioration are reviewed.

Conclusions

Indications for OBS following radical cystectomy in patients with invasive bladder cancer have significantly widened over the past 2 decades. An OBS should be offered to both male and female patients in the absence of contraindications. Good long-term functional and oncologic outcomes can be achieved in patients with OBS treated in high-volume institutions by experienced surgeons with specific knowledge in the field. Preoperative patient information, patient selection, surgical techniques, and careful postoperative follow-up are the cornerstones to achieve good long-term results.     

Effect of short recovery intensities on the performance during two Wingate tests

PURPOSE: To assess the effects of the intensity of short recoveries on performance by a Wingate test and on the deoxyhemoglobin variations. METHODS: Twelve male subjects performed a graded test and three sessions of repeated all-out tests with different recovery natures. The repeated all-out tests included two sprints: a 15-s Wingate test followed by a 30-s Wingate test. The recovery between the two was 15 s in duration and was either passive, active at 20% of maximal aerobic power, or active at 40% of maximal aerobic power. Changes in deoxyhemoglobin were measured using by the near-infrared spectroscopy technique. RESULTS: Mean power (517 +/- 26 W) and peak power (1085 +/- 153 W) of the 30-s Wingate test performed after passive recovery were significantly higher (P < 0.05) than mean power and peak power performed after active recovery at 20% (484 +/- 30 and 973 +/- 112 W, respectively) and 40% of maximal aerobic power (492 +/- 35 and 928 +/- 116 W, respectively). Deoxyhemoglobin variations were significantly higher (P < 0.05) during the passive recovery (12.8 +/- 5.3 microM) than during the active recovery conditions at 20% (4.3 +/- 2.6 microM) and 40% of maximal aerobic power (3.9 +/- 2.6 microM). CONCLUSION: These results demonstrate that when two Wingate tests are performed almost successively but with a short recovery between the two, passive recovery is more appropriate than active recovery to restore the performance level.     

Aristolochic acid nephropathy revisited: a place for innate and adaptive immunity?

Pozdzik A A, Berton A, Schmeiser H H, Missoum W, Decaestecker C, Salmon I J, Vanherweghem J‐L & Nortier J L
(2010) Histopathology 56 , 449–463 Aristolochic acid nephropathy revisited: a place for innate and adaptive immunity? Aims: The histological features of aristolochic acid nephropathy (AAN) consist of paucicellular interstitial fibrosis, severe tubular atrophy, and almost intact glomeruli with media lesions of interlobular arteries. As an early phase of interstitial inflammation preceded peritubular fibrosis in the rat model of AAN, the aim was to investigate the presence of inflammatory cells in human AAN. Methods and results: Reports of confirmed cases and case series of AAN were reviewed in terms of interstitial inflammation and found to have very conflicting results. This prompted us to search for and characterize inflammatory cells within the native kidneys provided from four end‐stage AAN patients. Prior aristolochic acid exposure was attested by the intrarenal presence of the typical aristolactam I‐derived DNA adduct. Besides the tubulointerstitial lesions usually seen in the cortex, a massive infiltration of macrophages, T and B lymphocytes was detected by immunohistochemistry in the medullary rays and in the outer medullae with some extension to the upper cortical labyrinth. Conclusions: In parallel with histological findings reported in the rat model, inflammatory cells are present preferentially in the interstitium of the medullary rays and of the outer medulllae in renal interstitium from human AAN cases, even in the terminal stages. Further studies must be undertaken to determine the respective roles of innate and adaptive immunity in the progression of AAN.