ALK-rearranged renal cell carcinoma with TPM3::ALK gene fusion and review of the literature.

ALK-rearranged renal cell carcinoma (ALK-RCC) is a very rare novel molecularly defined entity in the recently published fifth edition of the World Health Organization classification of tumours. We describe a case of ALK-RCC in a 76-year-old female. The tumour was composed of discohesive rhabdoid cells and pleomorphic, multinucleated cells (equivalent to ISUP/WHO grade 4). The tumour showed expression with PAX8, Keratin 7 and alpha methylacyl CoA racemase. ALK (D5F3 clone) was strongly and diffusely positive. ALK-FISH showed significant split signals of ALK, confirming the diagnosis. RNA sequencing showed TPM3::ALK rearrangement. Including the current case, there are 14 reported ALK-RCC cases with the same TPM3 fusion partner gene. Review of these published cases highlights their morphological heterogeneity and stresses the importance of running ALK immunohistochemistry on difficult cases to classify renal tumours. This is important while identification of ALK-RCC has clinical significance due to the availability of targeted therapy with ALK inhibitors.

The Detection of Prostate Cancer with Magnetic Resonance Imaging-Targeted Prostate Biopsies is Superior with the Transperineal vs the Transrectal Approach. A European Association of Urology-Young Academic Urologists Prostate Cancer Working Group Multi-Institutional Study.

PURPOSE: Our aim was to evaluate whether transperineal (TP) MRI-targeted prostate biopsy (TBx) may improve the detection of clinically significant prostate cancer (csPCa), defined as International Society of Urological Pathology ≥2, in comparison to transrectal (TR) TBx. MATERIALS AND METHODS: A multicenter retrospective cohort study comprising patients who underwent MRI-guided prostate biopsy was conducted. To address possible benefits of TP-TBx in the detection of prostate cancer (PCa) and csPCa, a cohort of patients undergoing TP-TBx were compared to patients undergoing TR-TBx. Multivariable logistic regression analyses were performed to assess predictors of PCa and csPCa detection. RESULTS: Overall, 1,936 and 3,305 patients who underwent TR-TBx vs TP-TBx at 10 referral centers were enrolled. The rate of PCa and csPCa diagnosed was higher for TP-TBx vs TR-TBx (64.0% vs 50%, p <0.01 and 49% vs 35%, p <0.01). At multivariable analysis adjusted for age, biopsy naïve/repeated biopsy, cT stage, Prostate Imaging-Reporting and Data System®, prostate volume, PSA, and number of biopsy cores targeted, TP-TBx was an independent predictor of PCa (odds ratio [OR] 1.37, 95% CI 1.08-1.72) and csPCa (1.19, 95% CI 1.12-1.50). When considering the approach according to the site of the index lesion, TP-TBx had a significantly higher likelihood than TR-TBx to detect csPCa in the apex (OR 4.81, 95% CI 1.03-6.27), transition/central zone (OR 2.67, 95% CI 1.42-5.00), and anterior zone (OR 5.62, 95% CI 1.74-8.13). CONCLUSIONS: The use of TP-TBx allows a better cancer grade definition and PCa risk assessment. This has important implication in the decision-making process and in patient counseling for further therapies.

Ductal variant prostate carcinoma is associated with a significantly shorter metastasis-free survival.

BACKGROUND: Ductal adenocarcinoma is an uncommon prostate cancer variant. Previous studies suggest that ductal variant histology may be associated with worse clinical outcomes, but these are difficult to interpret. To address this, we performed an international, multi-institutional study to describe the characteristics of ductal adenocarcinoma, particularly focussing on the effect of presence of ductal variant cancer on metastasis-free survival. METHODS: Patients with ductal variant histology from two institutional databases who underwent radical prostatectomies were identified and compared with an independent acinar adenocarcinoma cohort. After propensity score matching, the effect of the presence of ductal adenocarcinoma on time to biochemical recurrence, initiation of salvage therapy and the development of metastatic disease was determined. Deep whole-exome sequencing was performed for selected cases (n = 8). RESULTS: A total of 202 ductal adenocarcinoma and 2037 acinar adenocarcinoma cases were analysed. Survival analysis after matching demonstrated that patients with ductal variant histology had shorter salvage-free survival (8.1 versus 22.0 months, p = 0.03) and metastasis-free survival (6.7 versus 78.6 months, p < 0.0001). Ductal variant histology was consistently associated with RB1 loss, as well as copy number gains in TAP1, SLC4A2 and EHHADH. CONCLUSIONS: The presence of any ductal variant adenocarcinoma at the time of prostatectomy portends a worse clinical outcome than pure acinar cancers, with significantly shorter times to initiation of salvage therapies and the onset of metastatic disease. These features appear to be driven by uncoupling of chromosomal duplication from cell division, resulting in widespread copy number aberration with specific gain of genes implicated in treatment resistance.

Recurrent UTIs and cystitis symptoms in women.

BACKGROUND: Recurrent urinary tract infections (rUTIs) and recurrent cystitis symptoms without infection occur commonly in women and present frequently in general practice. OBJECTIVE: The aim of this article is to provide a management approach to the assessment and treatment of recurrent cystitis symptoms in women with rUTIs as well as women who have negative urine cultures. DISCUSSION: Five common clinical scenarios are discussed with different approaches to treatment: true rUTIs with positive urine cultures, women with variable urine cultures (some positive and some negative), women with negative urine cultures who have pyuria +/- haematuria, women with completely normal urine cultures and women with ongoing symptoms after a definite UTI. Red flags signalling the need for early referral to a urologist for further assessment are discussed. Both non-antibiotic and antibiotic-related strategies to treat women with rUTIs are available.

Predictors of erectile dysfunction after transperineal template prostate biopsy.

PURPOSE: To investigate the incidence and possible contributing factors of erectile dysfunction (ED) after transperineal template prostate biopsy (TTPB). MATERIALS AND METHODS: Males undergoing TTPB were prospectively administered a Sexual Health Inventory for Men (SHIM) questionnaire before biopsy and one month after. SHIM questionnaires were repeated at 3- and 9-months for males not receiving interventional treatment. Sexually inactive males were excluded. Interval change in SHIM categories based upon baseline characteristics were evaluated. Multivariable logistic regression models were used to evaluate predictors of change in SHIM score category. RESULTS: A total of 576 males were included in our sample. Of these, 450 (78%) males underwent their first biopsy. A decline in SHIM category within the immediate 4-weeks post-biopsy was reported by 167 males (31% of total eligible sample). Age was the strongest predictor of decline in SHIM category, the predicted probability of a decline in SHIM at age 50 was 10% (95% confidence interval [CI], 1%-19%), 32% at age 60 (95% CI, 25%-40%) and 36% at age 70 (95% CI, 29%-44%). For new onset ED, the predicted probability of ED within 4-weeks post-TTPB were 6.7% at age 50 (95% CI, 0%-15%), 26% at age 60 (95% CI, 17%-34%) and 31% at age 70 (95% CI, 21%-40%). CONCLUSIONS: Older age at biopsy is an independent predictor of immediate ED after TTPB in sexually active males. This association was observed in the subgroup with no pre-existing ED. These findings provide useful information when counselling males undergoing TTPB.

Comparison of perioperative, renal and oncologic outcomes in robotic-assisted versus open partial nephrectomy.

BACKGROUND: To compare perioperative, renal and oncological outcomes after robotic-assisted partial nephrectomy (RAPN) versus open partial nephrectomy (OPN) for the treatment of renal tumours. METHODS: All partial nephrectomies performed at a Metropolitan Urology Centre between 2010 and 2016 were analysed. Baseline data was collected for patient demographics, tumour characteristics (tumour size, laterality and polarity, RENAL scores), and perioperative variables (e.g. warm ischaemic time, operation time, estimated blood loss (EBL), length of stay). Tumour characteristics included malignancy, clinical stage, Fuhrman nuclear grade and surgical margin status. Day-1 post-operative serum creatinine, estimated glomerular filtration rate (eGFR) and 6-month eGFR stage were used for assessing renal function. RESULTS: Two hundred patients underwent partial nephrectomy between 2010 and 2016 (n = 200; 55 OPN versus 145 RAPN). Baseline data was similar between groups, except for lower age (P = 0.0001) and higher RENAL scores (P = 0.001) in the RAPN group. RAPN demonstrated significantly lower complication rates (P = 0.015), lesser EBL (P = <0.0001), shorter hospital stays (P = <0.001) and reduced positive tumour resection margins (P = 0.039). There was no significant difference in mean operation time between RAPN and OPN (137.2 (±48.0) OPN versus 146.07 (±35.91) RAPN; P = 0.16). No statistical difference was shown for post-operative eGFR stage between groups at Day-1 and 6-month post-surgery (P = 0.15 and P = 0.861, respectively). CONCLUSION: We present the largest reported Australian series on partial nephrectomy, confirming that a robotic-assisted approach is equivalent to OPN, with reduced complications, EBL, length of hospital stays and fewer positive margins, even when resecting more complex tumours.

Lower risk of pelvic metalware infection with operative repair of concurrent bladder rupture.

BACKGROUND: Patients with traumatic bladder rupture frequently have associated pelvic fracture. With increasing numbers of pelvic fractures fixed internally, there are concerns that conservative management of bladder rupture may increase the risk of pelvic metalware infection. This study aims to determine if operative repair of bladder rupture in comparison to conservative management with catheter drainage alone is associated with a lower rate of infection of internal fixation device for concurrent pelvic fracture. METHODS: This is a retrospective cohort study of level IV evidence. From July 2001 through June 2013, 45 multi-trauma patients at a level 1 trauma centre were identified to have sustained bladder rupture with concurrent pelvic fracture requiring internal fixation. Clinicopathological data were extracted from the TraumaNET database, medical records and health-coding database. Patients were stratified into two retrospective cohorts, management with surgical repair and management with catheter drainage alone. Fischer's exact test was used to determine whether the rate of pelvic metalware infection was different in the two cohorts. RESULTS: Of the 45 patients, 13 had intraperitoneal bladder rupture, 28 had extraperitoneal bladder rupture and four had combined intra-extraperitoneal bladder rupture. The median age for this cohort was 31. Bladder rupture was surgically repaired in 36 patients and managed conservatively with catheter drainage in nine patients. The rate of pelvic internal fixation device infection was lower in patients managed with surgical repair compared with conservative management (5.6% versus 33.3%, P = 0.047). CONCLUSION: Operative repair of bladder rupture is associated with a lower rate of pelvic orthopaedic hardware infection in the presence of concurrent pelvic fracture requiring internal fixation.

Zero hospital admissions for infection after 577 transperineal prostate biopsies using single-dose cephazolin prophylaxis.

PURPOSE: To determine the rate of hospital admissions for infection after transperineal biopsy of prostate (TPB) with single-dose cephazolin prophylaxis using a prospective database. METHOD: Between April 2013 and February 2016, 577 patients undergoing TPB had 2 g of cephazolin given intravenously at induction of anaesthesia. Data collected from these patients included age, PSA, prostate volume, number of cores taken and post-operative complications. RESULTS: No patients were readmitted to hospital with infection post-TPB. Seven patients developed acute urinary retention, and one patient developed clinical prostatitis that was treated with oral antibiotics in the community. CONCLUSION: It is safe to use single-dose cephazolin only as antibiotic prophylaxis prior to TPB, negating the need for quinolones. This study supports Australia's current Therapeutic Guidelines recommendation for TPB prophylaxis and the existing evidence that sepsis post-TPB is a rare complication. Whether any antibiotic prophylaxis is needed at all for TPB is the subject of a future study.

Beware of the 'Ascites' Patient: Delayed Presentation of Traumatic Intraperitoneal Bladder Rupture.

Delayed diagnosis of an intraperitoneal bladder rupture is rare in the post CT era. We present a case of a middle aged male with a delayed presentation of a traumatic intraperitoneal bladder rupture. He initially presented with an acute distended abdomen and acute kidney injury after an alleged assault. He was initially admitted for investigation of his 'ascites.' This case to our knowledge is the longest delay to diagnosis (>2 weeks) for an intraperitoneal bladder rupture in the post computed tomography era and should serve as a learning point in the workup of the patient with suspected blunt bladder injury.