De Novo Urological Malignancies After Renal Transplantation: An Asian 30-Year Experience.

BACKGROUND: As the incidence of urological malignancies after renal transplantation (RT) is observed to be greater than in the general population, a better understanding of them is important. We present our experience with urological tumors in RT recipients at our transplant center, and analyze their incidence, management and outcomes. MATERIALS AND METHODS: A retrospective analysis of 2177 RT recipients on follow-up at our center between 1990 and 2022 was conducted for de novo genitourinary malignancy. Patients diagnosed with malignancy before transplantation were excluded. Clinicopathological data at diagnosis and follow-up were collected and analyzed. Kaplan-Meier estimates were used to evaluate overall survival (OS) and cancer-specific survival (CSS). Statistical analysis was performed using IBM SPSS v.24 (IBM Corp., Armonk, NY, USA). RESULTS: The overall incidence of Urological malignancies was 3.9%, with 89 cancers diagnosed in 85 patients. Renal cell carcinoma was most common (n = 61, 68.5%), followed by prostate cancer (n = 10, 11.2%), urothelial carcinoma (n = 10, 11.2%), squamous cell carcinoma of the penis/scrotum (n = 7, 7.9%), and testicular cancer (n = 1, 1.1%). Mean duration between transplantation and diagnosis of malignancy was 9.9 (0.4-20.7) years. At a median follow-up of 4.6 (018.2) years, 27 deaths were seen; 7(25.9%) were due to urological malignancy. CSS rates were 86% and 78% at five and ten years, respectively, after diagnosis. CONCLUSION: We present one of the largest series of de novo urological malignancies observed over an extended 30-year follow-up of RT recipients, demonstrating an elevated risk in line with other studies. Regular surveillance for malignancies is advised, in order to ensure early diagnosis and management.

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.

Off-clamp vs on-clamp robot-assisted partial nephrectomy: a systematic review and meta-analysis.

OBJECTIVE: To compare intra- and postoperative outcomes between off-clamp and on-clamp robot-assisted partial nephrectomy (RAPN), using data from randomised controlled trials (RCTs) or covariate-matched studies (propensity score-matched or matched-pair analysis). METHODS: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant literature review was conducted on PubMed, EMBASE, Scopus and CENTRAL for relevant studies comparing off-clamp to on-clamp RAPN. Primary outcomes were estimated blood loss, postoperative percentage decrease in estimated glomerular filtration rate (eGFR), and margin positive rate. Secondary outcomes were operative time, postoperative eGFR, length of stay, all postoperative complications, major complications, and need for transfusion. Random-effects meta-analyses were performed to generate mean differences (MDs) or odds ratios (ORs). RESULTS: A total of 10 studies (2307 patients) were shortlisted for analysis. There was no significant difference in estimated operative blood loss between off-clamp and on-clamp RAPN (MD 21.9 mL, 95% confidence interval [CI] -0.9 to 44.7 mL; P = 0.06, I2 = 58%). Off-clamp RAPN yielded a smaller postoperative eGFR deterioration (MD 3.10%, 95% CI 1.05-5.16%; P = 0.008, I2 = 13%) and lower odds of margin positivity (OR 0.62, 95% CI 0.40-0.94; P = 0.03, I2 = 0%). No significant differences were found for all secondary outcomes. CONCLUSIONS: Off-clamp and on-clamp RAPN are similarly effective approaches for selected renal masses. Within the classic trifecta of PN outcomes, off-clamp RAPN yields similar rates of perioperative complications and may possibly offer better preservation of renal function and reduced margin-positive rates.

Single versus multiple renal arteries in living donor kidney transplantation: A systematic review and patient-level meta-analysis.

INTRODUCTION: Grafts with multiple renal arteries (MRAs) were historically considered a relative contraindication to transplantation due to the higher risk of vascular and urologic complications. This study aimed to evaluate graft and patient survival between single renal artery (SRA) and MRA living-donor kidney transplants. METHODS: An electronic literature search was conducted on PubMed, EMBASE, and Scopus for prospective or retrospective studies comparing SRA versus MRA in living donor renal transplantation, with the provision of Kaplan-Meier curves for recipient overall survival (OS) or graft survival (GS). A graphical reconstructive algorithm was used to obtain OS and GS of individual patients, which was then pooled under random-effects individual patient data (IPD) meta-analysis using Cox-models to determine hazard ratios (HRs) and 95% confidence intervals (CIs). Meta-regression of baseline covariates versus HRs of OS and GS was performed for variables reported in 10 or more studies. RESULTS: Fourteen studies were retrieved, of which 13 (8400 patients) reported OS and 9 (6912 patients) reported GS. There were no significant differences in OS (shared-frailty HR = .94, 95%CI = .85-1.03, p = .172) or GS (shared-frailty HR = .95, 95%CI = .83-1.08, p = .419) between SRA and MRA. This comparison remained non-significant even when restricted to open- or laparoscopic-only studies. Meta-regression yielded no significant associations of GS with donor age, recipient age, and percentage of double renal arteries within the MRA arm. CONCLUSIONS: The similar rates of GS and OS between MRA and SRA grafts suggest that there is no need for discrimination between the two when evaluating donors for nephrectomy.

Managing a Renal Transplant Programme During the COVID-19 Pandemic: Practical Experience from a Singapore Transplant Centre.

INTRODUCTION: Coronavirus Disease 2019 (COVID-19) has significantly affected the way healthcare is delivered in Singapore. Healthcare services such as renal transplantation had to rapidly adjust and meet the needs to (1) protect patients and staff, (2) ramp up, conserve or redeploy resources while (3) ensuring that critical services remained operational. This paper aims to describe the experience of the renal transplant programme at the Singapore General Hospital (SGH) in responding to the risks and constraints posed by the pandemic. METHODS AND MATERIALS: This is a review and summary of the SGH renal transplant programme's policy and protocols that were either modified or developed in response to the COVID-19 Pandemic. RESULTS: A multi-pronged approach was adopted to respond to the challenges of COVID-19. These included ensuring business continuity by splitting the transplant team into different locations, adopting video and tele-consults to minimise potential patient exposure to COVID-19, streamlining work processes using electronic forms, ensuring safe paths for patients who needed to come to hospital, ring-fencing and testing new inpatients at risk for COVID-19, enhancing precautionary measures for transplant surgery, ensuring a stable supply chain of immunosuppression, and sustaining patient and staff education programmes via video conferencing. CONCLUSIONS: Though the COVID-19 pandemic has reduced access to kidney transplantation, opportunities arose to adopt telemedicine into mainstream transplant practice as well as use electronic platforms to streamline work processes. Screening protocols were established to ensure that transplantation could be performed safely, while webinars reached out to empower patients to take precautions against COVID-19.

A Contemporary Analysis of Outcomes and Modifiable Risk Factors of Ethnic Disparities in Kidney Transplantation.

OBJECTIVE: The aim of this study was to provide a contemporary analysis of longitudinal kidney transplant outcomes and to evaluate potential causes of ethnic disparities among African American (AA) and Caucasian American (CA) patients undergoing kidney transplantation at our institution. PATIENTS AND METHODS: 1400 patients were identified who underwent kidney transplantation from 2003 to 2013 from a large, academic institution in Cleveland, OH. Relevant recipient and donor demographic and clinical covariates were obtained from an institutional transplant database. Simple descriptive statistics and comparative survival analyses were performed to assess overall survival and graft survival. RESULTS: The final cohort was comprised of 341 AA and 1059 CA patients. AAs were less likely to receive a living donor transplant (27.6% vs. 57.2%, p < 0.001) compared to CAs. Overall patient survival did not significantly differ between the two groups even when stratified by ethnicity. However, AAs had a significantly lower rate of graft survival (p < 0.001). On stratified analysis, there was no difference in the rate of graft survival among AAs and CAs who received living donor grafts. On univariate analysis, AAs demonstrated higher rates of immunosuppression non-compliance and chronic rejection (both p < 0.05). On multivariate analysis, AA recipient ethnicity (HR 1.56, p = 0.047), recipient history of diabetes (HR 1.67, p < 0.001), and AA donor ethnicity (HR 1.56, p = 0.047) were significantly associated with graft failure. CONCLUSION: AAs undergoing deceased donor renal transplantation demonstrated lower graft survival compared to CAs. Conversely, this disparity did not exist among AAs undergoing living donor transplantation. AAs had higher rates of deceased donor transplantation, immunosuppression non-compliance, chronic rejection, and diabetes. Opportunities exist to use patient education, alternative immunosuppression regimens, and living transplantation to close the ethnic disparity in renal allograft survival.

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.

TFE3-Expressing Epithelioid Rich Perivascular Epithelioid Cell Neoplasm (PEComa) of the Bladder with Unusual Benign Course.

Perivascular epithelioid cell tumor (PEComa) is an uncommon tumor which presents with epithelioid and spindled cell morphology and is immunoreactive for myogenic and melanocytic markers. Recently, a subset of PEComas has been reported to harbor TFE3 gene rearrangement.In this case report, we describe a TFE3-expressing primary bladder PEComa in a 27-year-old male patient with acute myeloid leukaemia in remission. The tumor displayed epithelioid morphology with surrounding delicate blood vessels and was devoid of a prominent spindle cell component. Malignant features were not identified. The tumor expressed HMB45, CD117, and focal patchy positive expression for SMA. TFE3 gene translocation was confirmed by Fluorescence in-situ hybridization. RT-PCR assay confirmed the presence of SFPQ-TFE3 gene fusion.In contrast to previously reported aggressive TFE3 gene-rearranged bladder PEComa cases, our case shows benign histologic and clinical features. Current clinical follow-up also shows a benign course.

Does periprostatic block increase the transrectal ultrasound (TRUS) biopsy sepsis rate in men with elevated PSA?

INTRODUCTION: Periprostatic nerve block (PPNB) is a common local anaesthetic technique in transrectal ultrasound-guided (TRUS) prostate biopsy, but concerns remain over the increased theoretical risks of urinary tract infection (UTI) and sepsis from the additional transrectal needle punctures. This study reviewed our biopsy data to assess this risk. MATERIALS AND METHODS: Retrospective data collected from 177 men who underwent TRUS biopsy between July 2007 and December 2009 in a single institution were analysed. PPNB was administered using 1% xylocaine at the prostatic base and apex and repeated on the contralateral side under ultrasound guidance. Complications, including UTI sepsis, bleeding per rectum and acute retention of urine (ARU) were noted. Every patient was tracked for the first 2 weeks for complications until his clinic review. Demographic profi le, biopsy parameters and histological fi ndings were reviewed. Univariate and multivariate analysis of possible risk factors for development of sepsis after TRUS biopsy were performed. Statistical analysis was performed using SPSS 17.0. RESULTS: Ninety (51%) men received PPNB and 87 (49%) did not. The groups were matched in age (PPNB: mean 62.7 ± 5.8 years; without PPNB: mean 64.4 ± 5.7 years) and prebiopsy prostate specific antigen (PSA) levels (PPNB: mean 8.2 ± 3.9 ng/mL; without PPNB: mean 8.3 ± 3.7 ng/mL). The PPNB group had a larger prostate volume, with more cores taken (P <0.05). On univariate and multivariate analysis controlling for age, PSA, prostate volume, number of cores taken and histological prostatitis, PPNB was not a significant risk factor for sepsis. Sepsis rates were 5.6% in the PPNB group and 5.7% in the other group (P = 0.956). Overall prostate cancer detection rate was 33.3%. CONCLUSION: The risk of sepsis was not increased in patients who received PPNB, even though this group had larger gland volumes and more biopsy cores taken.

Negative regulatory responses to metabolically triggered inflammation impair renal epithelial immunity in diabetes mellitus.

Diabetes mellitus is characterized by chronic inflammation and increased risk of infections, particularly of tissues exposed to the external environment. However, the causal molecular mechanisms that affect immune cells and their functions in diabetes are unclear. Here we show, by transcript and protein analyses, signatures of glucose-induced tissue damage, chronic inflammation, oxidative stress, and dysregulated expression of multiple inflammation- and immunity-related molecules in diabetic kidneys compared with non-diabetic controls. Abnormal signaling involving cytokines, G-protein coupled receptors, protein kinase C isoforms, mitogen-activated protein kinases, nuclear factor-κB (NFκB), and Toll-like receptors (TLR) were evident. These were accompanied by overexpression of negative regulators of NFκB, TLR, and other proinflammatory pathways, e.g., A20, SOCS1, IRAK-M, IκBα, Triad3A, Tollip, SIGIRR, and ST2L. Anti-inflammatory and immunomodulatory molecules, e.g., IL-10, IL-4, and TSLP that favor TH2 responses were strongly induced. These molecular indicators of immune dysfunction led us to detect the cryptic presence of bacteria and human cytomegalovirus in more than one third of kidneys of diabetic subjects but none in non-diabetic kidneys. Similar signaling abnormalities could be induced in primary human renal tubular epithelial (but not mesangial) cell cultures exposed to high glucose, proinflammatory cytokines and methylglyoxal, and were reversed by combined pharmacological treatment with an antioxidant and a PKC inhibitor. Our results suggest that diabetes impairs epithelial immunity as a consequence of chronic and inappropriate activation of counter-regulatory immune responses, which are otherwise physiological protective mechanisms against inflammation. The immune abnormalities and cryptic renal infections described here may contribute to progression of diabetic nephropathy.