A rare case of fatal rectal perforation and sepsis following traumatic urinary catheterization.

This case report details a fatal rectal perforation and sepsis in a comorbid 96-year-old male after traumatic urinary catheterization, highlighting the risks of IDC management in elderly patients with complex health backgrounds. Despite maximal medical therapy, including escalated antibiotics and ICU care, the patient died from septic shock linked to improper catheter insertion by a non-specialist nurse in the community. This case emphasizes the urgent need for better catheterization practices, specialized nursing education, and clear guidelines to prevent such outcomes.

Improved early and late continence following robot-assisted radical prostatectomy with concurrent bladder neck fascial sling (RoboSling).

Objective: To describe a novel RoboSling technique performed at the time of robot-assisted radical prostatectomy (RARP) and its utility for enhancing urinary function recovery postoperatively. Materials and Methods: The surgical technique involves harvesting a vascularised, fascial flap from the peritoneum on the posterior aspect of the bladder. Following completion of prostatectomy, the autologous flap is tunnelled underneath the bladder and incorporated into the rectourethralis and vertical longitudinal detrusor fibres at the posterior bladder neck with a modified Rocco suture. After urethra-vesical anastomosis is completed, the corners of the flap are hitched up to Cooper's ligament bilaterally with V-Loc sutures, tensioned and secured creating a bladder neck sling. A prospective, longitudinal cohort study was performed of 193 consecutive patients undergoing RARP between December 2016 and September 2019. The first 163 patients underwent standard RARP, and the last 30 patients had the RoboSling technique performed concurrently. Continence outcomes were the primary outcomes assessed using pad number and Expanded Prostate Cancer Composite (EPIC)-urinary domain questionnaire. Operative time (OT), estimated blood loss (EBL), complications and oncological outcomes were secondary outcomes. Results: The two groups were comparable for demographics and clinicopathological variables. At 3 months, zero pad usage (p = 0.005) and continence rates, defined as EPIC score ≥ 85 (p = 0.007), were both higher in the RoboSling group. EBL, complication rate and positive surgical margin rate did not differ between the two groups. Superior zero pad usage was observed at 1 year in the RoboSling group (p = 0.029). The RoboSling technique added on average 16 min to OT. Conclusions: The RoboSling procedure at the time of RARP was associated with earlier return to continence without negatively impacting other postoperative outcomes. This improvement in continence outcomes was maintained long term.

Implementation of a clinical practice guideline for assessment and management of renal colic in the emergency department.

INTRODUCTION: Renal colic is a common emergency department (ED) presentation. Variations in assessment and management of suspected renal colic may have significant implications on patient and hospital outcomes. We developed a clinical practice guideline to standardize the assessment and management of renal colic in the ED. We subsequently compared outcomes before and after guideline implementation. METHODS: The guideline standardizes the analgesia regimen, urology consult criteria, imaging modality, patient education, and followup instructions. This is a single-center, observational cohort study of patients presenting to the ED with renal colic prospectively collected after guideline implementation (December 2018 to May 2019) compared to a control group retrospectively collected before guideline implementation (December 2017 to May 2018). A total of 528 patients (pre-guideline n=283, post-guideline n=245) were included. Statistical analysis was performed with SPSS using multivariate linear regression. RESULTS: ED length of stay (LOS) was significantly shorter after guideline implementation (pre-guideline 295.82±178.8 minutes vs. post-guideline 253.2±118.2 minutes, p=0.017). The number of computed tomography (CT) scans patients received was significantly less after guideline implementation (pre guideline 1.35±1.34 vs. post-guideline 1.00±0.68, p=0.034). Patients discharged for conservative management had a lower re-presentation rate in the post-guideline group (12.6%) than the pre-guideline group (17.2%); however, this did not reach statistical significance (p=0.18). CONCLUSIONS: Implementation of a clinical practice guideline for ureteric stones reduces the ED LOS and the total number of CT scan in patients who present with renal colic. Standardizing assessment and management of ureteric stones can potentially improve patient and hospital outcomes without compromising the quality of care.

Is Size All That Matters? New Predictors of Complications and Bleeding in Renal Angiomyolipoma.

Purpose: Renal angiomyolipoma (AML) is the most common benign renal tumor. Whilst generally asymptomatic, they can cause life-threatening bleeding. Selective angioembolization (SAE) may be used to treat large symptomatic and asymptomatic AMLs. We aimed to evaluate the efficacy of SAE for symptomatic and asymptomatic renal AMLs and determine characteristics that predict spontaneous bleeding. Patients and Methods: Data were retrospectively collected from a prospectively maintained database from July 2011 to April 2022. Patients were included if AML was >4cm and they underwent subsequent SAE. Follow-up imaging was analyzed to calculate mean reduction in AML size. Clinical notes were reviewed to analyze lesion characteristics including vascularity, fat content and presence of aneurysm as well as post-procedural complications. Results: 26 patients with 30 AMLs were identified. Interval of follow-up imaging ranged from 1 to 60 months. 25 AMLs were embolized electively with 5 emergency embolizations performed for bleeding. Mean reduction in AML volume was 41% at 3 months (p=0.013) and 63% at 12 months (p=0.007). All 5 bleeding AMLs had a rich vascularity with 60% also having either aneurysms or a low fat content. Complications included post-embolic syndrome (n=9), segmental renal parenchyma devascularization (n=3), acute bleeding requiring re-embolization (n=2), nephrectomy for ongoing bleeding (n=1) and delayed bleeding managed conservatively (n=1). No deterioration in renal function was observed. Conclusion: SAE is an effective procedure for managing symptomatic and asymptomatic renal AML, with minimal significant complications. AML vascularity, fat content and aneurysms may be useful characteristics to assess future risk of bleeding in patients with renal AML.

An approach to evaluating scrotal skin-based lesions: A case report of Basal Cell Carcinoma of the Scrotum in patient with multiple risk factors.

Basal cell carcinoma (BCC) is rare on non-sun exposed skin such as the scrotum and thus diagnosis is often delayed. This case highlights an approach to scrotal skin lesions, risk factors and diagnostic features of BCC. Importantly, scrotal BCCs are more likely to metastasise than non-scrotal BCCs. Management should consist of wide local excision and recommended follow up with thorough clinical history, skin examination and imaging in high-risk patients.

A challenging case of surgical management of a single ischemic testicle from severe epididymo-orchitis.

A 41 years-old male patient presented acutely with severe right testicular pain, and fever for 48 hours. Patient had a backround of previous left orchidectomy for epididymo-orchitis and sexually-transmitted disease. A clinical diagnosis of right epididymo-orchitis was made and patient was treated with intravenous broad-spectrum antibiotic. However subsequent ultrasound revealed imminent testicular ischaemia. Given the challenging nature of the case, i.e. single testicle with testicular ischaemia, surgical exploration, fasciotomy and tunica vaginalis grafting was performed to the patient. The patient recovered fully post-operatively with ultrasound proving restoration of end-diastolic flow to the testicle.

Sensitization of prostate cancer to radiation therapy: Molecules and pathways to target.

Radiation therapy is used to treat cancer by radiation-induced DNA damage. Despite the best efforts to eliminate cancer, some cancer cells survive irradiation, resulting in cancer progression or recurrence. Alteration in DNA damage repair pathways is common in cancers, resulting in modulation of their response to radiation. This article focuses on the recent findings about molecules and pathways that potentially can be targeted to sensitize prostate cancer cells to ionizing radiation, thereby achieving an improved therapeutic outcome.

Measurement and modeling of diffusion time dependence of apparent diffusion coefficient and fractional anisotropy in prostate tissue ex vivo.

The purpose of this study was to measure and model the diffusion time dependence of apparent diffusion coefficient (ADC) and fractional anisotropy (FA) derived from conventional prostate diffusion-weighted imaging methods as used in recommended multiparametric MRI protocols. Diffusion tensor imaging (DTI) was performed at 9.4 T with three radical prostatectomy specimens, with diffusion times in the range 10-120 ms and b-values 0-3000 s/mm2 . ADC and FA were calculated from DTI measurements at b-values of 800 and 1600 s/mm2 . Independently, a two-component model (restricted isotropic plus Gaussian anisotropic) was used to synthesize DTI data, from which ADC and FA were predicted and compared with the measured values. Measured ADC and FA exhibited a diffusion time dependence, which was closely predicted by the two-component model. ADC decreased by about 0.10-0.15 µm2 /ms as diffusion time increased from 10 to 120 ms. FA increased with diffusion time at b-values of 800 and 1600 s/mm2 but was predicted to be independent of diffusion time at b = 3000 s/mm2 . Both ADC and FA exhibited diffusion time dependence that could be modeled as two unmixed water pools - one having isotropic restricted dynamics, and the other unrestricted anisotropic dynamics. These results highlight the importance of considering and reporting diffusion times in conventional ADC and FA calculations and protocol recommendations, and inform the development of improved diffusion methods for prostate cancer imaging.

Urological complications after cystectomy as part of pelvic exenteration are higher than that after cystectomy for primary bladder malignancy.

BACKGROUND: Total cystectomy and subsequent reconstruction of the urinary tract may be required for primary malignancy of the bladder, or in the context of multi-visceral resection for more advanced pelvic tumors. Complications following urinary diversion are a major source of morbidity, particularly in pelvic exenteration (PE) patients. METHODS: All patients who underwent radical cystectomy alone or during PE at a single tertiary referral centre between 2008 and 2014 were reviewed. Postoperative urological complications were collected and compared between groups. RESULTS: Two hundred and thirty-one patients underwent en bloc cystectomy (98 cystectomy alone, 133 as part of a PE). Postoperative urological complications occurred in 33% of the cystectomy alone group and 59% of the PE group (P < 0.001). PE for recurrence had higher complications than PE for primary malignancy (67% vs. 48%, P = 0.035). Urological leaks occurred in 3%, 6%, and 14% of patient who had cystectomy alone, PE for primary malignancy and PE for recurrence. Major blood loss and previous pelvic radiotherapy independently predicted conduit-associated complications in PE patients (P = 0.002 and 0.035). CONCLUSIONS: Urological complications of cystectomy, particularly urine leaks and sepsis, are more common in patients undergoing PE compared to those with cystectomy alone. Prior pelvic radiotherapy, the extent of surgical resection and major blood loss may contribute to urological morbidity. J. Surg. Oncol. 2017;115:307-311. © 2016 Wiley Periodicals, Inc.

Information-based ranking of 10 compartment models of diffusion-weighted signal attenuation in fixed prostate tissue.

This study compares the theoretical information content of single- and multi-compartment models of diffusion-weighted signal attenuation in prostate tissue. Diffusion-weighted imaging (DWI) was performed at 9.4 T with multiple diffusion times and an extended range of b values in four whole formalin-fixed prostates. Ten models, including different combinations of isotropic, anisotropic and restricted components, were tested. Models were ranked using the Akaike information criterion. In all four prostates, two-component models, comprising an anisotropic Gaussian component and an isotropic restricted component, ranked highest in the majority of voxels. Single-component models, whether isotropic (apparent diffusion coefficient, ADC) or anisotropic (diffusion tensor imaging, DTI), consistently ranked lower than multi-component models. Model ranking trends were independent of voxel size and maximum b value in the range tested (1.6-16 mm(3) and 3000-10,000 s/mm(2)). This study characterizes the two major water components previously identified by biexponential models and shows that models incorporating both anisotropic and restricted components provide more information-rich descriptions of DWI signals in prostate tissue than single- or multi-component anisotropic models and models that do not account for restricted diffusion.

Diffusion anisotropy in fresh and fixed prostate tissue ex vivo.

PURPOSE: To investigate diffusion anisotropy in whole human prostate specimens METHODS: Seven whole radical prostatectomy specimens were obtained with informed patient consent and institutional ethics approval. Diffusion tensor imaging was performed at 9.4 Tesla. Diffusion tensors were calculated from the native acquired data and after progressive downsampling RESULTS: Fractional anisotropy (FA) decreased as voxel volume increased, and differed widely between prostates. Fixation decreased mean FA by ∼0.05-0.08 at all voxel volumes but did not alter principle eigenvector orientation. In unfixed tissue high FA (> 0.6) was found only in voxels of volume <0.5 mm(3) , and then only in a small fraction of all voxels. At typical clinical voxel volumes (4-16 mm(3) ) less than 50% of voxels had FA > 0.25. FA decreased at longer diffusion times (Δ = 60 or 80 ms compared with 20 ms), but only by ∼0.02 at typical clinical voxel volume. Peripheral zone FA was significantly lower than transition zone FA in five of the seven prostates CONCLUSION: FA varies widely between prostates. The very small proportion of clinical size voxels with high FA suggests that in clinical DWI studies ADC based on three-direction measurements will be minimally affected by anisotropy. Magn Reson Med 76:626-634, 2016. © 2015 Wiley Periodicals, Inc.

Targeting of cytosolic phospholipase A2α impedes cell cycle re-entry of quiescent prostate cancer cells.

Cell cycle re-entry of quiescent cancer cells has been proposed to be involved in cancer progression and recurrence. Cytosolic phospholipase A2α (cPLA2α) is an enzyme that hydrolyzes membrane glycerophospholipids to release arachidonic acid and lysophospholipids that are implicated in cancer cell proliferation. The aim of this study was to determine the role of cPLA2α in cell cycle re-entry of quiescent prostate cancer cells. When PC-3 and LNCaP cells were rendered to a quiescent state, the active form of cPLA2α with a phosphorylation at Ser505 was lower compared to their proliferating state. Conversely, the phospho-cPLA2α levels were resurgent during the induction of cell cycle re-entry. Pharmacological inhibition of cPLA2α with Efipladib upon induction of cell cycle re-entry inhibited the re-entry process, as manifested by refrained DNA synthesis, persistent high proportion of cells in G0/G1 and low percentage of cells in S and G2/M phases, together with a stagnant recovery of Ki-67 expression. Simultaneously, Efipladib prohibited the emergence of Skp2 while maintained p27 at a high level in the nuclear compartment during cell cycle re-entry. Inhibition of cPLA2α also prevented an accumulation of cyclin D1/CDK4, cyclin E/CDK2, phospho-pRb, pre-replicative complex proteins CDC6, MCM7, ORC6 and DNA synthesis-related protein PCNA during induction of cell cycle re-entry. Moreover, a pre-treatment of the prostate cancer cells with Efipladib during induction of cell cycle re-entry subsequently compromised their tumorigenic capacity in vivo. Hence, cPLA2α plays an important role in cell cycle re-entry by quiescent prostate cancer cells.

AKT and cytosolic phospholipase A2α form a positive loop in prostate cancer cells.

Aberrant increase in protein kinase B (AKT) phosphorylation (pAKT), due to a gain-of-function mutation of phosphatidylinositol-3-kinase (PI3K) or loss-of-function mutation or deletion of phosphatase and tensin homolog (PTEN), is a common alteration in prostate cancer and associated with poor prognosis. Cytosolic phospholipase A2α (cPLA2α) is a lipid modifying enzyme by catalyzing the hydrolysis of arachidonic acid from membrane phospholipid. The released arachidonic acid and its metabolites contribute to survival and proliferation of prostate cancer cells. In this mini-review, we summarize the relationship between pAKT and cPLA2α in prostate cancer cells. There was a concordant increase in pAKT and cPLA2α levels in prostate tissue of prostate epithelial-specific PTEN-knockout mice compared to PTEN-wild type mice. Restoration of PTEN expression or inhibition of PI3K action decreased cPLA2α expression in PTEN-mutated or deleted prostate cancer cells. An increase in AKT phosphorylation elevated, whereas inhibition of AKT phosphorylation diminished, cPLA2α protein levels. pAKT had no influence on cPLA2α expression at mRNA levels but stabilized cPLA2α at protein levels by protecting it from degradation. Conversely, an induction of cPLA2α expression led to an increase in pAKT levels in PTEN-mutated or deleted prostate cancer cells, while silencing of cPLA2α expression or pharmacological blocking cPLA2α action decreased pAKT levels. The diminishment of pAKT by either genetic silencing or pharmacological blocking of cPLA2α was mitigated by the addition of arachidonic acid. The stimulatory effect of arachidonic acid on pAKT levels was lessened by inhibiting the production of arachidonic acid metabolites. These studies have revealed a link between oncogenic pathway and lipid metabolism and provided potential molecular targets for treating prostate cancer.

Changes in Epithelium, Stroma, and Lumen Space Correlate More Strongly with Gleason Pattern and Are Stronger Predictors of Prostate ADC Changes than Cellularity Metrics.

PURPOSE: To investigate the hypothesis that the clinically observed decrease in apparent diffusion coefficient (ADC) at diffusion-weighted magnetic resonance imaging with increasing prostate cancer Gleason grade can be attributed to an increasing volume of low-diffusivity epithelial cells and corresponding decreasing volumes of higher-diffusivity stroma and lumen space rather than to increased cell density. MATERIALS AND METHODS: Tissue samples were acquired after institutional ethics review committee approval and informed consent from patients were obtained. Nuclear count, nuclear area, and gland component volumes (epithelium, stroma, lumen space) were measured in tissue from 14 patients. Gland component volumes and cellularity metrics were correlated with Gleason pattern (Spearman rank correlation coefficient) and measured ADC (Pearson correlation coefficient) in six prostates ex vivo. Differences between metrics for cancerous tissue and those for normal tissue were assessed by using a two-tailed two-sample t test. Linear mixed models with a post hoc Fisher least significant difference test were used to assess differences between gland component volumes and cellularity metrics for multiple groups. To adjust for a clustering effect due to repeated measures, the organ mean value of the measured metric for each tissue type was used in the analysis. RESULTS: There were significant differences between Gleason patterns for gland component volumes (P < .05) but not nuclear count (P = .100) or area (P = .141). There was a stronger correlation of Gleason pattern with gland component volumes (n = 553) of epithelium (Spearman ρ = 0.898, P < .001), stroma (ρ = -0.651, P < .001), and lumen space (ρ = -0.912, P = .007) than with the cellularity metrics (n = 288) nuclear area (ρ = 0.422, P = .133) or nuclear count (ρ = 0.082, P = .780). There was a stronger correlation between measured ADC and lumen volume (r = 0.688, P < .001) and epithelium volume (r = -0.647, P < .001) than between ADC and nuclear count (r = -0.598, P < .001) or nuclear area (r = -0.569, P < .001) (n = 57). CONCLUSION: Differences in the gland compartment volumes of prostate tissue having distinct diffusivities, rather than changes in the conventionally cited "cellularity" metrics, are likely to be the major contributor to clinically observed variations of ADC in prostate tissue.

Assessment of non-Gaussian diffusion with singly and doubly stretched biexponential models of diffusion-weighted MRI (DWI) signal attenuation in prostate tissue.

Non-Gaussian diffusion dynamics was investigated in the two distinct water populations identified by a biexponential model of diffusion in prostate tissue. Diffusion-weighted MRI (DWI) signal attenuation was measured ex vivo in two formalin-fixed prostates at 9.4 T with diffusion times Δ = 10, 20 and 40 ms, and b values in the range 0.017-8.2 ms/µm(2) . A conventional biexponential model was compared with models in which either the lower diffusivity component or both of the components of the biexponential were stretched. Models were compared using Akaike's Information Criterion (AIC) and a leave-one-out (LOO) test of model prediction accuracy. The doubly stretched (SS) model had the highest LOO prediction accuracy and lowest AIC (highest information content) in the majority of voxels at Δ = 10 and 20 ms. The lower diffusivity stretching factor (α2 ) of the SS model was consistently lower (range ~0.3-0.9) than the higher diffusivity stretching factor (α1 , range ~0.7-1.1), indicating a high degree of diffusion heterogeneity in the lower diffusivity environment, and nearly Gaussian diffusion in the higher diffusivity environment. Stretched biexponential models demonstrate that, in prostate tissue, the two distinct water populations identified by the simple biexponential model individually exhibit non-Gaussian diffusion dynamics.

Loss of PTEN stabilizes the lipid modifying enzyme cytosolic phospholipase A2α via AKT in prostate cancer cells.

Aberrant increase in pAKT, due to a gain-of-function mutation of PI3K or loss-of-function mutation or deletion of PTEN, occurs in prostate cancer and is associated with poor patient prognosis. Cytosolic phospholipase A2α (cPLA2α) is a lipid modifying enzyme by catalyzing the hydrolysis of membrane arachidonic acid. Arachidonic acid and its metabolites contribute to survival and proliferation of prostate cancer cells. We examined whether AKT plays a role in promoting cPLA2α action in prostate cancer cells. We found a concordant increase in pAKT and cPLA2α levels in prostate tissue of prostate epithelial-specific PTEN-knockout but not PTEN-wide type mice. Restoration of PTEN expression or inhibition of PI3K action decreased cPLA2α expression in PTEN-mutated or deleted prostate cancer cells. An increase in AKT by Myr-AKT elevated cPLA2α protein levels, which could be diminished by inhibition of AKT phosphorylation without noticeable change in total AKT levels. pAKT levels had no influence on cPLA2α at mRNA levels but reduced cPLA2α protein degradation. Anti-AKT antibody co-immunoprecipitated cPLA2α and vice versa. Hence, AKT plays a role in enhancing cPLA2α protein stability in PTEN-null prostate cancer cells, revealing a link between oncogenic pathway and lipid metabolism.

Information theoretic ranking of four models of diffusion attenuation in fresh and fixed prostate tissue ex vivo.

PURPOSE: To compare the theoretical information content of four popular models of diffusion-weighted signal attenuation. METHOD: Four whole prostates were imaged fresh unfixed and fixed at 9.4T. Biexponential, kurtosis, stretched exponential, and monoexponential models were ranked using Akaike's Information Criterion (AIC) with validation by a leave-one-out test of model prediction error. RESULTS: For unfixed tissue measurements (b-value range: 17-2104 s/mm(2)) the biexponential and kurtosis models had similar information content to each other and this was distinctly higher than for the stretched and monoexponential models. In fixed-tissue measurements (b-value range: 17-8252 s/mm(2)), the biexponential model had much higher information content than the three other models. CONCLUSION: AIC-based model ranking is consistent with an independent prediction accuracy test. Biexponential and kurtosis models consistently perform better than stretched and monoexponential models. The biexponential model has increasing superiority over all three other models as maximum b-value increases above ∼2000 s/mm(2).

ICUD-EAU International Consultation on Bladder Cancer 2012: Non-muscle-invasive urothelial carcinoma of the bladder.

CONTEXT: Our aim was to present a summary of the Second International Consultation on Bladder Cancer recommendations on the diagnosis and treatment options for non-muscle-invasive urothelial cancer of the bladder (NMIBC) using an evidence-based approach. OBJECTIVE: To critically review the recent data on the management of NMIBC to arrive at a general consensus. EVIDENCE ACQUISITION: A detailed Medline analysis was performed for original articles addressing the treatment of NMIBC with regard to diagnosis, surgery, intravesical chemotherapy, and follow-up. Proceedings from the last 5 yr of major conferences were also searched. EVIDENCE SYNTHESIS: The major findings are presented in an evidence-based fashion. We analyzed large retrospective and prospective studies. CONCLUSIONS: Urothelial cancer of the bladder staged Ta, T1, and carcinoma in situ (CIS), also indicated as NMIBC, poses greatly varying but uniformly demanding challenges to urologic care. On the one hand, the high recurrence rate and low progression rate with Ta low-grade demand risk-adapted treatment and surveillance to provide thorough care while minimizing treatment-related burden. On the other hand, the propensity of Ta high-grade, T1, and CIS to progress demands intense care and timely consideration of radical cystectomy.