Pneumoperitoneum and peritonitis secondary to perforation of an infected bladder.

INTRODUCTION AND IMPORTANCE: Spontaneous urinary bladder rupture is a rare complication of urosepsis. Its co-occurrence with pneumoperitoneum is even more unusual. CASE PRESENTATION: A 73-year-old patient presented with acute retention with mild lower abdominal pain and difficulty with urinary voiding and cystitis. He was treated with bladder catheter and antibiotics. After one month, he suddenly developed peritonitis and shock. Pneumoperitoneum was observed on a chest x-ray. An emergent laparotomy was performed and a perforation of the bladder secondary to necrosis of part of the wall was found and resected. The patient recovered satisfactorily after the surgical intervention. CLINICAL DISCUSSION: Spontaneous bladder rupture is a life-threatening condition that could be missed. Surgical intervention is mandatory to rule out other more probable causes of peritonitis and to manage the bladder perforation itself. CONCLUSION: Pneumoperitoneum is rarely secondary to a bladder perforation. Immediate surgical intervention is required in order to avoid delays in treating any intra-abdominal condition including a bladder wall perforation.

PPP2R2C loss promotes castration-resistance and is associated with increased prostate cancer-specific mortality.

Metastatic prostate cancers generally rely on androgen receptor (AR) signaling for growth and survival, even following systemic androgen-deprivation therapy (ADT). However, recent evidence suggests that some advanced prostate cancers escape ADT by using signaling programs and growth factors that bypass canonical AR ligand-mediated mechanisms. We used an in vitro high-throughput RNA interference (RNAi) screen to identify pathways in androgen-dependent prostate cancer cell lines whose loss-of-function promotes androgen ligand-independent growth. We identified 40 genes where knockdown promoted proliferation of both LNCaP and VCaP prostate cancer cells in the absence of androgen. Of these, 14 were downregulated in primary and metastatic prostate cancer, including two subunits of the protein phosphatase 2 (PP2A) holoenzyme complex: PPP2R1A, a structural subunit with known tumor-suppressor properties in several tumor types; and PPP2R2C, a PP2A substrate-binding regulatory subunit that has not been previously identified as a tumor suppressor. We show that loss of PPP2R2C promotes androgen ligand depletion-resistant prostate cancer growth without altering AR expression or canonical AR-regulated gene expression. Furthermore, cell proliferation induced by PPP2R2C loss was not inhibited by the AR antagonist MDV3100, indicating that PPP2R2C loss may promote growth independently of known AR-mediated transcriptional programs. Immunohistochemical analysis of PPP2R2C protein levels in primary prostate tumors determined that low PPP2R2C expression significantly associated with an increased likelihood of cancer recurrence and cancer-specific mortality. These findings provide insights into mechanisms by which prostate cancers resist AR-pathway suppression and support inhibiting PPP2R2C complexes or the growth pathway(s) activated by PPP2R2C as a therapeutic strategy.

The history and anatomy of urologic lymphadenectomy.

The history of urologic lymphadenectomy is rich and diverse. Our current understanding of its use and benefits is a product of the hard work of numerous physicians and scientists from many nations. Standard dissection templates for the various urologic malignancies are based on a complete understanding of the anatomy of the lymphatic system, which has developed immensely since Hippocrates first described the white blood of the lymphatic system while performing an axillary dissection. It is hoped that the next 100 years will bring even greater comprehension of its value and utility.

Genomic predictors of prostate cancer therapy outcomes.

Although numerous attempts have been made to forecast outcomes for prostate cancer after therapy using clinical and histological variables, the ability to accurately predict an individual's response to a specific treatment remains elusive. Recently, major advances in the field of genomics have made possible the near-comprehensive assessment of the genetic status of tumor genomes, with major concentration on predicting an individual's response to a specific treatment. Genomic approaches to treatment response include, but are not limited to, detection of gene rearrangements, DNA copy-number aberrations, single-nucleotide polymorphisms, epigenetic changes and differential gene-expression patterns. These approaches have been used to predict response to treatment for local and systemic disease in multiple small cohorts. Further study with larger cohorts and longer follow-up should result in more concordance among genomic approaches, and will enable physicians to gain insight into the heterogeneity of supposedly 'similar' cancers and help tailor treatments accordingly.

Treatment of BCG failures with intravesical BCG/Interferon: the University of Montreal experience.

OBJECTIVE: Bacillus Calmette-Guerin (BCG) has shown promise in large scale studies. We assessed recurrence-free survival in patients treated with intravesical BCG/Interferon (IFN) for non-muscle invasive, BCG refractory, transitional cell carcinoma (TCC) of the urinary bladder at our local institution. METHODS: Cancer control data were gathered for patients enrolled in a BCG/Interferon protocol at the University of Montreal. The main inclusion criteria consisted of pathologically proven evidence of intravesical BCG failure, and of complete transurethral resection of latest post BCG recurrence. Induction consisted of eight intravesical BCG/Interferon instillations. Select patients were treated with BCG/Interferon maintenance therapy. RESULTS: Thirteen patients aged from 45 to 81 years (mean: 65) were included. Stages at TCC diagnosis were distributed as follows: 6 (46%) CIS, 3 (23%) Ta, and 4 (31%) T1. Induction BCG consisted of an average of 11 weekly instillations (range 3-24). Prior to BCG/Interferon stage distribution was as follows: 9 (69%) CIS, and 4 (31%) T1. BCG/Interferon maintenance was administered to 5 (38%) patients. Follow-up ranged from 1.5 to 32 months (mean=15, median=12). Recurrence was diagnosed in 5 patients (38%). Recurrence free survival (RFS) at 24 months was 66%. When stratified according to T stage prior to BCG/IFN, patients with CIS fared worse than T1 patients (50% versus 100%). Maintenance had no effect on RFS (75% versus 69%). CONCLUSIONS: Our results corroborate previous BCG/IFN reports. In selected patients, intravesical BCG/IFN offers a valid alternative to definitive therapy.

Prostate specific-antigen distribution in asymptomatic Canadian men with no clinical evidence of prostate cancer.

OBJECTIVE: To examine prostate specific-antigen (PSA) levels and percentage free/total PSA (f/tPSA) distributions as well as digital rectal examination (DRE) profiles in asymptomatic Canadian men with no established prostate cancer diagnosis, as recent data indicate that a man's risk of developing prostate cancer is higher if his baseline PSA level is above the median for his age group. SUBJECTS AND METHODS: We used data obtained during an early prostate cancer-detection event. An invitation to an onsite DRE, PSA level and f/tPSA assessment was accepted by 313 men. Serum PSA level and f/tPSA were measured before the DRE. A suspicious DRE and/or PSA level of > or = 2.5 ng/mL or f/tPSA of < or = 15% represented indications for a systematic 12-core ultrasonography-guided prostate biopsy. RESULTS: Of all the 313 men, most (235, 75%) had PSA levels of 0.01-1.53 ng/mL and an f/tPSA of >15% (285, 91.1%). The median (range) PSA level was 0.8 (0-34.2) ng/mL and f/tPSA was 27.4 (6.7-100)%. Age-specific median PSA levels and f/tPSA were, respectively, 0.7, 0.9, 1.0, 1.5 ng/mL and 31%, 27%, 26%, 25% for men aged 40-49, 50-59, 60-69 and 70-79 years. A suspicious DRE was recorded in 55 (17.6%) men, with eight (8.8%), 26 (20.0%), 14 (20.6%), and seven (28.9%) having suspicious DRE findings according to above age categories. Overall, seven (2.2%) prostate cancers were detected. CONCLUSION: The median age-specific baseline PSA levels and f/tPSA represent valuable indicators of prostate cancer risk. The population-specific baseline median PSA level should not be >1.0 ng/mL and the baseline f/tPSA should be >30%. Men with values outside of these ranges should be considered at greater risk of prostate cancer.

Normal urinary and sexual function in men without evidence of prostate cancer from Montreal, Canada.

OBJECTIVE: To examine the rates of stress urinary incontinence (SUI) and erectile dysfunction (ED), and of associated bother, in men with no evidence of prostate cancer who participated in a prostate cancer-screening event. SUBJECTS AND METHODS: A cohort of 366 men with no established diagnosis of prostate cancer completed a questionnaire addressing SUI, ED and associated bother. Socio-economic status and presence of comorbidities were also examined. RESULTS: The mean (range) age of the men was 54.8 (33-80) years; 90% of the men (271) had no SUI, and 76% (231) reported no urinary bother. Conversely, 62% (189) reported some degree of ED and 27% (82) some degree of sexual bother. Urinary bother (P < 0.001), erectile function (P < 0.001), and sexual bother (P < 0.02) were associated with age. Of all the men, 36% had one or more comorbidities. Men with one or more comorbidities had worse erectile function than those men with no comorbidity (P < 0.05). CONCLUSION: Few studies address normative values of SUI and ED rates in men with no established diagnosis of prostate cancer. We quantified the rate of SUI and it was practically negligible. Conversely, some degree of ED affected most of the present screened population. These data may be used as baseline references to evaluate the magnitude of functional and bother detriments after various prostate treatments.

Tumor size improves the accuracy of TNM predictions in patients with renal cancer.

OBJECTIVES: Current staging for renal cancer (RC) does not directly rely on tumor size. We examined the increment in accuracy related to inclusion of pathologically determined tumor size in prediction of nodal metastases (N+), distant metastases (M+), and cancer-specific survival (CSS). METHODS: Partial or radical nephrectomy was performed in 2245 patients with clear cell histology. Pathologic stages were T1a in 566, T1b in 490, T2 in 303, T3 in 831, and T4 in 55 patients. Tumor size was 0.5-25 cm (mean, 6.8). Multivariate models relied on 1997 and 2002 TNM variables and addressed N+, M+ disease, and CCS. Their accuracy was compared according to either the presence or absence of tumor size. RESULTS: In all univariate and multivariate models, tumor size was a statistically significant predictor of all outcomes (p< or =0.001). In all multivariate models, tumor size added between 3.7% and 0.8% to predictive accuracy of either 1997 or 2002 TNM categories. CONCLUSIONS: Tumor size represents a highly significant, multivariate, and informative predictor of RC outcomes and may warrant inclusion in future TNM revisions.

Familial retinal migraines.

Approximately 25% of sufferers of retinal migraine are thought to have a positive family history. Retinal migraines can cause both transient, and rarely permanent, unilateral monocular visual loss. This report of familial retinal migraines furthers our understanding of this particular migraine subtype. Two families with retinal migraines are reported suggesting an autosomal-dominant inheritance pattern with variable expression and penetrance.