Radiomics in Kidney Transplantation: A Scoping Review of Current Applications, Limitations, and Future Directions.

Radiomics is increasingly applied to the diagnosis, management, and outcome prediction of various urological conditions. The purpose of this scoping review is to evaluate the current evidence of the application of radiomics in kidney transplantation, especially its utility in diagnostics and therapeutics. An electronic literature search on radiomics in the setting of transplantation was conducted on PubMed, EMBASE, and Scopus from inception to September 23, 2022. A total of 16 studies were included. The most widely studied clinical utility of radiomics in kidney transplantation is its use as an adjunct to diagnose rejection, potentially reducing the need for unnecessary biopsies or guiding decisions for earlier biopsies to optimize graft survival. Technology such as optical coherence tomography is a noninvasive procedure to build high-resolution optical cross-section images of the kidney cortex in situ and in real time, which can provide histopathological information of donor kidney candidates for transplantation, and to predict posttransplant function. This review shows that, although radiomics in kidney transplants is still in its infancy, it has the potential for large-scale implementation. Its greatest potential lies in the correlation with conventional established diagnostic evaluation for living donors and potential in predicting and detecting rejection postoperatively.

Graft retrieval incisions in minimally invasive donor nephrectomy: Systematic review and network meta-analysis.

BACKGROUND: Various incisions are employed for graft extraction during minimally invasive donor nephrectomy, but an overarching synthesis of associated short-term donor outcomes is lacking. METHODS: An electronic literature search was conducted on PubMed, EMBASE and Scopus for studies comparing ≥2 graft extraction incisions in laparoscopic or robotic donor nephrectomy with ≥10 patients per arm. Eligible study designs included randomized trials, case-control, and cohort studies. Primary outcomes were donor length of stay (LOS); in-hospital analgesic requirement; and postoperative complications. Secondary outcomes were warm ischemia time (WIT), total operation time (TOT), and estimated blood loss (EBL). Random-effects Frequentist network meta-analyses were conducted for all outcomes. RESULTS: Twenty-nine studies (4702 patients) were shortlisted. Six incisions were analyzed: iliac, Pfannenstiel, midline hand-assisted laparoscopic (HAL), midline umbilical, flank and transvaginal natural orifice transluminal endoscopic surgery (NOTES). The flank incision had significantly longer LOS than all other incisions. LOS was significantly longer in Pfannenstiel than iliac incision (mean difference [MD] = 0.29, 95%CI = 0.002-0.58 days). Midline HAL had significantly shorter TOT than most other incisions. Midline umbilical incisions had significantly higher WIT than midline HAL and Pfannenstiel incisions. Midline HAL had shorter WIT than transvaginal NOTES (MD = 0.80, 95%CI = 0.05-1.56 min). No major differences were seen in analgesia requirement, postoperative complications and EBL. CONCLUSION: Six different incisions for graft retrieval are broadly comparable across most short-term outcomes although long-term outcomes remain to be elucidated. Iliac and Pfannenstiel incisions yielded similar outcomes besides marginally lower LOS for the former. Midline incision for HAL may be associated with shorter TOT, and transvaginal NOTES is an effective technique for selected female donors. TRIAL REGISTRATION: PROSPERO CRD42023445407.

Cost-effectiveness of alternative first- and second-line treatments for benign prostatic hyperplasia in Singapore.

BACKGROUND: Minimally invasive surgical therapies, such as water vapor thermal therapy (WVTT) and prostatic urethral lift (PUL), are typically second-line options for patients in whom medical management (MM) failed but who are unwilling or unsuitable to undergo invasive transurethral resection of the prostate (TURP). However, the incremental cost-effectiveness of WVTT or PUL as first- or second-line therapy is unknown. We evaluated the incremental cost-effectiveness of alternative first- and second-line treatments for patients with moderate-to-severe benign prostatic hyperplasia (BPH) in Singapore to help policymakers make subsidy decisions based on value for money. METHODS: We considered six stepped-up treatment strategies, beginning with MM, WVTT, PUL or TURP. In each strategy, patients requiring retreatment advance to a more invasive treatment until TURP, which may be undergone twice. A Markov cohort model was used to simulate transitions between BPH severity states and retreatment, accruing costs and quality-adjusted life-years (QALYs) over a lifetime horizon. RESULTS: In moderate patients, strategies beginning with MM had similar cost and effectiveness, and first-line WVTT was incrementally cost-effective to first-line MM (33,307 SGD/QALY). First-line TURP was not incrementally cost-effective to first-line WVTT (159,361 SGD/QALY). For severe patients, WVTT was incrementally cost-effective to MM as a first-line treatment (30,133 SGD/QALY) and to TURP as a second-line treatment following MM (6877 SGD/QALY). TURP was incrementally cost-effective to WVTT as a first-line treatment (48,209 SGD/QALY) in severe patients only. All pathways involving PUL were dominated (higher costs and lower QALYs). CONCLUSION: Based on the common willingness-to-pay threshold of SGD 50,000/QALY, this study demonstrates the cost-effectiveness of WVTT over MM as first-line treatment for patients with moderate or severe BPH, suggesting it represents good value for money and should be considered for subsidy. PUL is not cost-effective as a first- nor second-line treatment. For patients with severe BPH, TURP as first-line is also cost-effective.

Benign prostatic hyperplasia (BPH) is a non-cancerous enlargement of the prostate, common among older men. Its symptoms include difficulties with starting and completing urination, incontinence, frequent and urgent need to urinate. Minimally invasive procedures, such as water vapor thermal therapy (WVTT) and prostatic urethral lift (PUL), are typically offered as second-line options to patients for whom medication has failed but who are unwilling or unsuitable to undergo invasive surgery (transurethral resection of the prostate, TURP). However, whether offering these procedures as first-line options represents good value for money (i.e. cost-effectiveness) is an open question. To address this question and inform subsidy decisions in Singapore, we investigated six stepped-up treatment strategies which differ in first- and second-line treatments. For each strategy, we simulated healthcare costs and quality of life for a cohort of moderate and severe BPH patients over their lifetime, considering the possibility of treatment-related adverse effects and multiple rounds of retreatment. The incremental cost of a unit improvement in quality of life for a strategy relative to the next most expensive one was compared against a willingness-to-pay threshold to determine cost-effectiveness. We found that WVTT was cost-effective relative to medication as a first-line treatment for patients with moderate or severe BPH, suggesting it represents good value for money and should be considered for subsidy. PUL was not cost-effective as first- nor second-line treatment. TURP is cost-effective as first-line for severe BPH patients only.

Development and Validation of a Deep Learning System for Sound-based Prediction of Urinary Flow.

BACKGROUND: Uroflowmetry remains an important tool for the assessment of patients with lower urinary tract symptoms (LUTS), but accuracy can be limited by within-subject variation of urinary flow rates. Voiding acoustics appear to correlate well with conventional uroflowmetry and show promise as a convenient home-based alternative for the monitoring of urinary flows. OBJECTIVE: To evaluate the ability of a sound-based deep learning algorithm (Audioflow) to predict uroflowmetry parameters and identify abnormal urinary flow patterns. DESIGN, SETTING, AND PARTICIPANTS: In this prospective open-label study, 534 male participants recruited at Singapore General Hospital between December 1, 2017 and July 1, 2019 voided into a uroflowmetry machine, and voiding acoustics were recorded using a smartphone in close proximity. The Audioflow algorithm consisted of two models-the first model for the prediction of flow parameters including maximum flow rate (Qmax), average flow rate (Qave), and voided volume (VV) was trained and validated using leave-one-out cross-validation procedures; the second model for discrimination of normal and abnormal urinary flows was trained based on a reference standard created by three senior urologists. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Lin's correlation coefficient was used to evaluate the agreement between Audioflow predictions and conventional uroflowmetry for Qmax, Qave, and VV. Accuracy of the Audioflow algorithm in the identification of abnormal urinary flows was assessed with sensitivity analyses and the area under the receiver operating curve (AUC); this algorithm was compared with an external panel of graders comprising six urology residents/general practitioners who separately graded flow patterns in the validation dataset. RESULTS AND LIMITATIONS: A total of 331 patients were included for analysis. Agreement between Audioflow and conventional uroflowmetry for Qmax, Qave, and VV was 0.77 (95% confidence interval [CI], 0.72-0.80), 0.85 (95% CI, 0.82-0.88) and 0.84 (95% CI, 0.80-0.87), respectively. For the identification of abnormal flows, Audioflow achieved a high rate of agreement of 83.8% (95% CI, 77.5-90.1%) with the reference standard, and was comparable with an external panel of six residents/general practitioners. AUC was 0.892 (95% CI, 0.834-0.951), with high sensitivity of 87.3% (95% CI, 76.8-93.7%) and specificity of 77.5% (95% CI, 61.1-88.6%). CONCLUSIONS: The results of this study suggest that a deep learning algorithm can predict uroflowmetry parameters and identify abnormal urinary voids based on voiding sounds, and shows promise as a simple home-based alternative to uroflowmetry in the management of patients with LUTS. PATIENT SUMMARY: In this study, we trained a deep learning-based algorithm to measure urinary flow rates and identify abnormal flow patterns based on voiding sounds. This may provide a convenient, home-based alternative to conventional uroflowmetry for the assessment and monitoring of patients with lower urinary tract symptoms.

Patient-reported outcomes of a phase II neoadjuvant apalutamide (ARN-509) and radical prostatectomy in treatment of intermediate- to high-risk prostate cancer (NEAR) trial.

OBJECTIVE: The NEAR trial is a single-arm phase II trial investigating the efficacy of neoadjuvant apalutamide and radical prostatectomy in the treatment of D'Amico intermediate- to high-risk prostate cancer. This publication focuses on health-related quality of life (HRQoL) during 12 weeks of neoadjuvant apalutamide treatment. METHODS: From 2017 to 2019, 30 suitable patients received neoadjuvant apalutamide 240 mg once daily for 12 weeks followed by radical prostatectomy (ClinicalTrials.gov Identifier: NCT03124433). Patient-reported quality of life outcomes was analyzed using European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core Module (EORTC QLQ-C30), EORTC Quality of Life Questionnaire Prostate Module (QLQ-PR25), and Sexual Health Inventory for Men questionnaire (SHIM) at weeks 0,4,12, and 20 of the study. RESULTS: Thirty patients completed 12 weeks of apalutamide therapy and data analyzed for 29 with complete datasets. Neoadjuvant apalutamide therapy was associated with no clinically significant negative impact on patients' global health and QoL scores. Deteriorations in mean scores of functional and symptom scales of QLQ-C30 questionnaire were statistically significant (p = 0.011 and p = 0.008, respectively) but were not clinically meaningful. Patients were also affected by fatigue (p = 0.012), cognitive function (p = 0.038), reduced role functioning (p = 0.025), and lower SHIM scores (p < 0.001). Median daily step count reduced from 8228/day to 6001/day per day (p = 0.063), while BMI and body weight reduction were observed (statistically but not clinically significant). CONCLUSION: During 12 weeks of neoadjuvant apalutamide in organ-confined prostate cancer, the overall patient-reported HRQoL outcomes were maintained, but fatigue and sexual dysfunction were observed in those patients.

NEAR trial: A single-arm phase II trial of neoadjuvant apalutamide monotherapy and radical prostatectomy in intermediate- and high-risk prostate cancer.

OBJECTIVE: Treatment efficacy of androgen deprivation therapy with radical prostatectomy for intermediate- to high-risk prostate cancer is less well-studied. The NEAR trial is a single-arm, phase II investigation of neoadjuvant apalutamide monotherapy and radical prostatectomy (RP) in the treatment of D'Amico intermediate- and high-risk prostate cancer (NCT03124433). MATERIALS AND METHODS: Patients with histologically-proven, D'Amico intermediate- to high-risk prostate adenocarcinoma received apalutamide 240 mg once-daily for 12 weeks followed by RP + /-lymphadenectomy. Primary outcome was pathological complete response (pCR) rate. Secondary outcomes included rate of biochemical response (defined by PSA < 0.03 ng/mL at week 24 from starting apalutamide without subsequent PSA relapse), treatment-related adverse events, and RP complication rates. Correlative biomarker analyses were performed to examine for molecular predictors of treatment responses. RESULTS: From 2017 to 2019, 30 patients were recruited, of which 20 and 10 were high and intermediate risk, respectively; 25 completed treatment as per-protocol. We did not observe any pCR on trial; median reduction of cancer burden was 41.7% (IQR: 33.3%-60.0%). 18 out of 25 patients were classified as having a biochemical response (4 did not achieve PSA of <0.03 ng/mL at week 24 and 3 developed PSA relapse subsequently). Dry skin (N = 16; 53.3%), fatigue (N = 10; 33.3%) and skin rash (N = 9; 30.0%) were the most common adverse events, and there was no major peri-operative complication. We observed an association between tumours of low androgen receptor activity and PAM50 basal status with biochemical non-responders, albeit these molecular phenotypes were not associated with pathological response. CONCLUSIONS: A 12-week course of neoadjuvant apalutamide prior to RP did not meet the primary endpoint of pCR in this trial. Tumours with low androgen receptor activity or of the PAM50 basal subtype may have a reduced response to apalutamide.

A Systemic Review and Meta-analysis of Transabdominal Intravesical Prostatic Protrusion Assessment in Determining Bladder Outlet Obstruction and Unsuccessful Trial Without Catheter.

CONTEXT: Urodynamic study (UDS) provides the most objective assessment of bladder outlet obstruction (BOO) but is impractical to be recommended routinely in outpatient services. Intravesical prostatic protrusion (IPP) had been described to obstruct urinary flow by creating an anatomical ball-valve effect, but there remains a lack of pooled evidence that can objectively correlate with BOO in benign prostatic hyperplasia. OBJECTIVE: To update the current evidence on the predictive role of IPP in determining BOO and unsuccessful trial without catheter (TWOC). EVIDENCE ACQUISITION: A comprehensive literature search was performed to identify studies that evaluated IPP in diagnosing UDS-determined BOO and TWOC. The search included the PubMed/MEDLINE, EMBASE, and Cochrane Library up to January 2021. An updated systemic review and meta-analysis was performed. EVIDENCE SYNTHESIS: A total of 18 studies with 4128 patients were examined. Eleven studies with 1478 patients examined the role of IPP in UDS-determined BOO. The pooled area under the curve (AUC) was 0.83 (95% confidence interval [CI]: 0.79-0.86), and at a cut-off of >10 mm, the sensitivity (Sn) and specificity (Sp) were 0.71 (95% CI: 0.61-0.78) and 0.77 (95% CI: 0.68-0.84), respectively. The probability-modifying plot revealed positive and negative likelihood ratios of 3.34 (95% CI: 2.56-4.36) and 0.35 (95% CI: 0.26-0.45), respectively. Seven studies with 2650 patients examined IPP in predicting unsuccessful TWOC, with a pooled AUC of 0.74 (95% CI: 0.70-0.84), with Sn of 0.51 (95% CI: 0.43-0.60) and Sp of 0.79 (95% CI: 0.73-0.84) at an IPP cut-off of >10 mm. Five studies compared prostate volume (PV) and IPP and revealed a lower AUC of PV at 0.71 (95% CI: 0.67-0.75), which was an inferior parameter in diagnosing BOO (p < 0.001). CONCLUSIONS: This systemic review provided evidence that IPP is a reliable clinical parameter that correlates strongly with underlying BOO and unsuccessful TWOC. PATIENT SUMMARY: In this review, we comprehensively reviewed all the literature to date on evaluating the clinical utility of intravesical prostatic protrusion (IPP). We have demonstrated that IPP correlates strongly with urodynamic study (UDS)-determined bladder outlet obstruction and failure of trial without catheter (TWOC). Outpatient IPP measurement is a quick, inexpensive, and reproducible clinical parameter that can determine the severity of benign prostatic hyperplasia. The clinical role of IPP in predicting failure of TWOC selects patients who are best treated with aggressive surgical approaches rather than conservative medical therapies. More importantly, IPP can facilitate the discriminatory use of invasive UDS, reserved for patients with a strong suspicion of concomitant detrusor abnormalities.

Defining prostate cancer size and treatment margin for focal therapy: does intralesional heterogeneity impact the performance of multiparametric MRI?

OBJECTIVES: To evaluate the impact of intralesional heterogeneity on the performance of multiparametric magnetic resonance imaging (mpMRI) in determining cancer extent and treatment margins for focal therapy (FT) of prostate cancer. PATIENTS AND METHODS: We identified men who underwent primary radical prostatectomy for organ- confined prostate cancer over a 3-year period. Cancer foci on whole-mount histology were marked out, coding low-grade (LG; Gleason 3) and high-grade (HG; Gleason 4-5) components separately. Measurements of entire tumours were grouped according to intralesional proportion of HG cancer: 0%, <50% and ≥50%; the readings were corrected for specimen shrinkage and correlated with matching lesions on mpMRI. Separate measurements were also taken of HG cancer components only, and correlated against entire lesions on mpMRI. Size discrepancies were used to derive the optimal tumour size and treatment margins for FT. RESULTS: There were 122 MRI-detected cancer lesions in 70 men. The mean linear specimen shrinkage was 8.4%. The overall correlation between histology and MRI dimensions was r = 0.79 (P < 0.001). Size correlation was superior for tumours with high burden (≥50%) compared to low burden (<50%) of HG cancer (r = 0.84 vs r = 0.63; P = 0.007). Size underestimation by mpMRI was more likely for larger tumours (51% for >12 mm vs 26% for ≤12 mm) and those containing HG cancer (44%, vs 20% for LG only). Size discrepancy analysis suggests an optimal tumour size of ≤12 mm and treatment margins of 5-6 mm for FT. For tumours ≤12 mm in diameter, applying 5- and 6-mm treatment margins would achieve 98.6% and 100% complete tumour ablation, respectively. For tumours of all sizes, using the same margins would ablate >95% of the HG cancer components. CONCLUSIONS: Multiparametric MRI performance in estimating prostate cancer size, and consequently the treatment margin for FT, is impacted by tumour size and the intralesional heterogeneity of cancer grades.

Multiparametric MRI reporting using Prostate Imaging Reporting and Data System version 2.0 (PI-RADSv2) retains clinical efficacy in a predominantly post-biopsy patient population.

OBJECTIVE: To evaluate the efficacy of multiparametric magnetic resonance imaging (mp-MRI) using Prostate Imaging Reporting and Data System version 2.0 (PI-RADSv2) definitions in detecting organ-confined prostate cancer. METHODS: All patients who underwent radical prostatectomy between January 1, 2014 and December 30, 2014 were identified. All underwent mp-MRI within 180 days before surgery. Those with prior pelvic irradiation or androgen deprivation therapy were excluded. Fully embedded, whole-mount histopathology was centrally reviewed and correlated with imaging for tumour location, Gleason score (GS) and stage. RESULTS: There were 39 patients included, of which 35 (90%) had mp-MRI done post-biopsy. A total of 93 cancer foci were identified on whole-mount pathology, of which mp-MRI detected 63 (68%). Of those detected by mp-MRI, 14 were PI-RADS 3 (n = 6 for GS 6, n = 8 for GS 7, no GS ≥ 8) and 49 were PI-RADS 4-5 (n = 7 for GS 6, n = 33 for GS 7, and n = 9 for GS ≥ 8). There were 30 (32%) cancer foci missed by mp-MRI (n = 15 for GS 6, n = 13 for GS 7 and n = 2 for GS ≥ 8). A lesion classified as PI-RADS 4-5 predicted a higher grade cancer on pathology as compared to PI-RADS 3 (for GS 7 lesions, odds ratio [OR] = 3.53, 95% CI: 0.93-13.45, p = 0.064). The mp-MRI size detection limit was 20 mm2 and 100 mm2 for 50% and 75% probability of cancer, respectively. In associating with radiological and pathologic stage, the weighted Kappa value was 0.69 (p < 0.0001). The sensitivity and positive predictive values for this study were 68% (95% CI: 57%-77%) and 78% (95% CI: 67%-86%), respectively. CONCLUSION: In this predominantly post-biopsy cohort, mp-MRI using PI-RADSv2 reporting has a reasonably high diagnostic accuracy in detecting clinically significant prostate cancer.

The Utility of Intraoperative Near Infrared Fluorescence (NIR) Imaging with Indocyanine Green (ICG) for the Assessment of Kidney Allograft Perfusion.

BACKGROUND: Near infrared light (NIR) fluorescence imaging with indocyanine green (ICG) has been used in various aspects of surgery, such as in the assessment of vascular anastomosis, tissue perfusion, and the identification of lymph nodes. In this study we evaluated the utility of NIR/ICG fluorescence imaging in kidney transplantation. MATERIALS AND METHODS: NIR/ICG imaging was used to assess allograft perfusion in n=1 living donor (LDRT) and n=2 deceased donor (DDRT) renal transplantations, performed in February 2017. The allograft arterial and venous anastomoses were done end-to-side to the corresponding recipient external iliacs, and ureteroneocystostomies were performed for urinary reconstructions. After completion of vascular anastomosis, ICG was given as intravenous bolus at 0.3mg/kg, followed by visual assessment of tissue perfusion and vascular anastomoses at 1-minute interval using fluorescence imaging (KARL STORZ NIR/ICG System). RESULTS: Homogenous global fluorescence of the allograft and vascular anastomosis was observed in all 3 cases. Immediate postoperative perfusion studies showed patent inflow and outflow vessels and well perfused transplanted kidneys. Immediate graft function was observed in 2 recipients (1 LDRT and 1 DDRT). One session of haemodialysis was performed in 1 DDRT recipient, for high serum potassium in the immediate postoperative setting, who otherwise had good urine output and serially declining serum creatinine. CONCLUSIONS: NIR/ICG fluorescence imaging can be useful in renal transplantation for the intraoperative assessment of allograft perfusion, especially in complex cases with multiple renal arteries and vascular reconstructions.

A rare case of isolated castrate resistant bilateral testicular metastases in advanced prostate cancer.

Testicular metastasis is rare with the prostate being the most common site of primary cancer. We report a case of a 72-year-old man with castration-resistant prostate cancer (CRPC) and known metastases to bone and lymph nodes, who developed bilateral painful swollen testes 3 years after the initial diagnosis of prostate cancer. He had first presented with lower urinary tract symptoms (LUTS) with suspicious findings on digital rectal examination of the prostate, and an elevated serum prostate specific antigen (PSA) level of 129 ng/mL. Transrectal prostate biopsy revealed Gleason 4 + 5 adenocarcinoma. Radiological staging showed locally advanced prostate cancer with extensive metastases to bone and pelvic and retroperitoneal lymph nodes. He was given hormonal therapy for over 2 years until progression to CRPC. Six months later he developed painful bilateral testicular swellings, and serum markers for testicular germ cell cancer were normal. Bilateral orchiectomy was performed, showing metastatic prostate cancer (Gleason 4 + 5) on histology. One month postoperatively his PSA level dropped to 0.1 ng/mL from a presurgery level of 6.24 ng/mL.

Use of the anterolateral thigh and vertical rectus abdominis musculocutaneous flaps as utility flaps in reconstructing large groin defects.

BACKGROUND: Groin dissections result in large wounds with exposed femoral vessels requiring soft tissue coverage, and the reconstructive options are diverse. In this study we reviewed our experience with the use of the pedicled anterolateral thigh and vertical rectus abdominis musculocutaneous flaps in the reconstruction of large groin wounds. METHODS: Groin reconstructions performed over a period of 10 years were evaluated, with a mean follow up of two years. We included all cases with large or complex (involving perineum) defects, which were reconstructed with the pedicled anterolateral thigh musculocutaneous or the vertical rectus abdominis musculocutaneous (VRAM) flaps. Smaller wounds which were covered with skin grafts, locally based flaps and pedicled muscle flaps were excluded. RESULTS: Twenty-three reconstructions were performed for large or complex groin defects, utilising the anterolateral thigh (n=10) and the vertical rectus abdominis (n=13) pedicled musculocutaneous flaps. Femoral vein reconstruction with a prosthetic graft was required in one patient, and a combination flap (VRAM and gracilis muscle flap) was performed in another. Satisfactory coverage was achieved in all cases without major complications. No free flaps were used in our series. CONCLUSIONS: The anterolateral thigh and vertical rectus abdominis pedicled musculocutaneous flaps yielded consistent results with little morbidity in the reconstruction of large and complex groin defects. A combination of flaps can be used in cases requiring extensive cover.