Simultaneous Robotic-Assisted Bilateral Native Nephrectomy and Kidney Transplantation for Autosomal Dominant Polycystic Kidney Disease in Recipients With High Body Mass Index: Report of 2 Cases.

Robotic kidney transplantation is a safe, reproducible, and less morbid technique in high body mass index and end-stage renal disease. Polycystic kidney disease is a relative contraindication to robotic-assisted kidney transplantation because of the mass effect of the native kidneys on the patient's pelvis that prevents ideal exposure. We report the first 2 cases of robotic-assisted simultaneous bilateral nephrectomy and kidney transplantation for patients with obesity and adult polycystic kidney disease. The recipients were 2 males, 50 and 53 years old, with a body mass index of 35.1 41.6 kg/m2 and 41.6 kg/m2, respectively. Both recipients had suitable living donors. The average operating time was 395 minutes and the estimated blood loss was on average 250 mL. The postoperative course was uneventful and the patients were discharged home on days 4 and 5. Performing robotic nephrectomies simultaneously with kidney transplantation can be done safely, allowing patients with obesity and polycystic kidney disease needing bilateral nephrectomy, to take full advantage of minimally invasive kidney transplantation.

Chyle Leak After Robotic Living Donor Nephrectomy: Literature Review And Management.

Chyle leak after living donor nephrectomy is a rare complication and is associated with a significant postoperative burden. To the best of our knowledge, only 1 case of chyle leak after robotic living donor nephrectomy has been reported in the literature. In this study, we present our experience with 2 cases of chyle leak: 1 after and 1 during robotic donor nephrectomy. We discuss previously published studies and man - agement options of chyle leak in kidney donors.

Rarely Described Renal Malignancies Associated With Venous Tumor Thrombus.

BACKGROUND/AIM: Collecting duct carcinoma, epithelioid angiosarcoma and neuroendocrine/carcinoid tumor are uncommon renal malignancies, and their association with tumor thrombus extending into the inferior vena cava is extremely rare. Owing to the rarity of the above-mentioned malignancies and short follow-up of the cases published in the literature, the prognosis and clinical behavior of these tumors remains unclear. Up to date, the culprit of treatment is surgical management with radical nephrectomy, lymph node dissection, thrombectomy and vascular reconstruction if necessary. PATIENTS AND METHODS: We herein describe in detail the first cases published of the above-mentioned renal malignancies associated with extensive inferior vena cava (IVC) thrombus, in which complex vascular reconstruction was performed. RESULTS: Three male patients were identified as having collecting duct carcinoma, epithelioid angiosarcoma and neuroendocrine/carcinoid tumor with IVC involvement. Tumor thrombus levels were II, I and IIIc respectively. Patient ages were 42, 60 and 47 years and tumor sizes were 9.2, 10.9 and 3.7 cm correspondingly. Patient 2 underwent cavectomy, IVC replacement using polytetrafluoroethylene (Gore-Tex®) vascular graft and IVC filter deployment inside the graft. None of the patients developed any pulmonary emboli postoperatively. At the last follow-up, IVC graft for patient 2 remained patent. CONCLUSION: Owing to the rarity of the aforementioned malignancies and short follow-up of cases published in the literature, the prognosis and clinical behavior of these tumors remains unclear. Up to date, the culprit of treatment is surgical management with radical nephrectomy, lymph node dissection, thrombectomy and vascular reconstruction if necessary. Polytetrafluoroethylene (Gore-Tex) vascular grafts are an excellent and safe option for complex vascular reconstructions in patients with evidence of IVC invasion.

Regulation of SARS CoV-2 host factors in the kidney and heart in rats with 5/6 nephrectomy-effects of salt, ARB, DPP4 inhibitor and SGLT2 blocker.

BACKGROUND: Host factors such as angiotensin-converting enzyme 2 (ACE2) and the transmembrane protease, serine-subtype-2 (TMPRSS2) are important factors for SARS-CoV-2 infection. Clinical and pre-clinical studies demonstrated that RAAS-blocking agents can be safely used during a SARS-CoV-2 infection but it is unknown if DPP-4 inhibitors or SGLT2-blockers may promote COVID-19 by increasing the host viral entry enzymes ACE2 and TMPRSS2. METHODS: We investigated telmisartan, linagliptin and empagliflozin induced effects on renal and cardiac expression of ACE2, TMPRSS2 and key enzymes involved in RAAS (REN, AGTR2, AGT) under high-salt conditions in a non-diabetic experimental 5/6 nephrectomy (5/6 Nx) model. In the present study, the gene expression of Ace2, Tmprss2, Ren, Agtr2 and Agt was assessed with qRT-PCR and the protein expression of ACE2 and TMPRSS2 with immunohistochemistry in the following experimental groups: Sham + normal diet (ND) + placebo (PBO); 5/6Nx + ND + PBO; 5/6Nx + high salt-diet (HSD) + PBO; 5/6Nx + HSD + telmisartan; 5/6Nx + HSD + linagliptin; 5/6Nx + HSD + empagliflozin. RESULTS: In the kidney, the expression of Ace2 was not altered on mRNA level under disease and treatment conditions. The renal TMPRSS2 levels (mRNA and protein) were not affected, whereas the cardiac level was significantly increased in 5/6Nx rats. Intriguingly, the elevated TMPRSS2 protein expression in the heart was significantly normalized after treatment with telmisartan, linagliptin and empagliflozin. CONCLUSIONS: Our study indicated that there is no upregulation regarding host factors potentially promoting SARS-CoV-2 virus entry into host cells when the SGLT2-blocker empagliflozin, telmisartan and the DPP4-inhibitor blocker linagliptin are used. The results obtained in a preclinical, experimental non-diabetic kidney failure model need confirmation in ongoing interventional clinical trials.

Large and rapid local recurrence of clear cell renal cell carcinoma.

After radical nephrectomy, clear cell renal cell carcinoma (ccRCC) recurs locally in <3% of patients. Recurrences typically occur 1-2 years postoperatively and grow at 5-20 mm per year. In contrast, this patient's recurrence was unexpectedly large and swift. A 71-year-old woman was initially found on workup for recurrent urinary tract infections to have a 12 cm left renal tumour. After negative staging scans, she progressed to left open radical nephrectomy. Histology revealed a stage T2b 12 cm ccRCCwith sarcomatoid differentiation, International Society of Urological Pathology (ISUP) grade 4, with clear margins. Only 3 months later, the patient developed left-sided abdominal pain, and CT scans revealed a 15 cm left retroperitoneal local recurrence, as well as widespread peritoneal tumours. In discussion with her treating team, the patient and her family elected not to undergo biopsy or systemic therapy. The patient was palliated and passed away 8 days after re-presentation.

ROBOCOP II (ROBOtic assisted versus conventional open partial nephrectomy) randomised, controlled feasibility trial: clinical trial protocol.

INTRODUCTION: Randomised controlled trials comparing robotic-assisted partial nephrectomy (RAPN) and open PN (OPN) are lacking. Therefore, we aim to report the study protocol and a trial update for a randomised controlled feasibility trial comparing RAPN versus OPN for renal neoplasms. METHODS AND ANALYSIS: The ROBOtic assisted versus conventional Open Partial nephrectomy II trial is designed as a single-centre, randomised, open-label, feasibility trial. Participation will be offered to patients with renal neoplasms and deemed feasible for both, OPN and RAPN. We aim to enrol 50 patients within 15 months using a 1:1 allocation ratio. The primary endpoint of the trial is feasibility of recruitment and will be successful if one third of eligible patients agree to participate. Secondary endpoints include perioperative results, health-related quality of life, inflammatory response as well as surgical ergonomics of the operating team. If the primary outcome, feasibility of recruitment, is successful, the secondary results of the trial will be used for planning a confirmative phase III trial. ETHICS AND DISSEMINATION: Ethical approval was obtained from the local institutional review board (Ethik-Kommission II at Heidelberg University: 2020-542N). Results will be made publicly available in peer-reviewed scientific journals and presented at appropriate congresses and social media. TRIAL REGISTRATION NUMBER: NCT04534998.

Histopathologic findings on indication renal allograft biopsies after recovery from acute COVID-19.

Current knowledge on histopathological changes occurring after COVID-19 in transplanted kidneys is limited. Herein, we present renal allograft pathology findings in patients recovered from COVID-19. Six patients underwent indication biopsy, and one required allograft nephrectomy after acute COVID-19. Demographic data, clinical characteristics, and laboratory findings were recorded. The histopathological analysis included light microscopy, immunostaining, and electron microscopy. Five patients were hospitalized for acute COVID-19, and all were diagnosed with imaging-confirmed pneumonia, one requiring mechanical ventilation, and two requiring dialysis. Two patients had mild form. Histopathologic examination of renal allograft specimens revealed collapsing, perihilar, tip-lesion and secondary FSGS in one patient each. One patient had borderline acute cellular rejection, and two had chronic antibody-mediated rejection. Histopathologic changes of glomerular tufts were accompanied by acute tubular injury in four patients. None of our patients had signs of viral inclusions in kidney cells. One patient died and one remained dialysis-dependent after the good initial response to treatment. Patients with collapsing and perihilar FSGS had further progression of their chronic allograft nephropathy still without need for dialysis. In conclusion, diverse kidney pathology may be found in SARS-CoV-2-infected renal transplant patients. It seems that viral infection may affect the immune system with triggering of glomerular diseases, while the acute tubular injury is of multifactorial etiology. Direct viral effect is less likely.

Delayed surgery for localised and metastatic renal cell carcinoma: a systematic review and meta-analysis for the COVID-19 pandemic.

PURPOSE: The COVID-19 pandemic has led to the cancellation or deferment of many elective cancer surgeries. We performed a systematic review on the oncological effects of delayed surgery for patients with localised or metastatic renal cell carcinoma (RCC) in the targeted therapy (TT) era. METHOD: The protocol of this review is registered on PROSPERO(CRD42020190882). A comprehensive literature search was performed on Medline, Embase and Cochrane CENTRAL using MeSH terms and keywords for randomised controlled trials and observational studies on the topic. Risks of biases were assessed using the Cochrane RoB tool and the Newcastle-Ottawa Scale. For localised RCC, immediate surgery [including partial nephrectomy (PN) and radical nephrectomy (RN)] and delayed surgery [including active surveillance (AS) and delayed intervention (DI)] were compared. For metastatic RCC, upfront versus deferred cytoreductive nephrectomy (CN) were compared. RESULTS: Eleven studies were included for quantitative analysis. Delayed surgery was significantly associated with worse cancer-specific survival (HR 1.67, 95% CI 1.23-2.27, p < 0.01) in T1a RCC, but no significant difference was noted for overall survival. For localised ≥ T1b RCC, there were insufficient data for meta-analysis and the results from the individual reports were contradictory. For metastatic RCC, upfront TT followed by deferred CN was associated with better overall survival when compared to upfront CN followed by deferred TT (HR 0.61, 95% CI 0.43-0.86, p < 0.001). CONCLUSION: Noting potential selection bias, there is insufficient evidence to support the notion that delayed surgery is safe in localised RCC. For metastatic RCC, upfront TT followed by deferred CN should be considered.

Impact of the first surge of the COVID-19 pandemic on a tertiary referral centre for kidney cancer.

OBJECTIVE: To analyse the impact of the COVID-19 pandemic on a centralized specialist kidney cancer care pathway. MATERIALS AND METHODS: We conducted a retrospective analysis of patient and pathway characteristics including prioritization strategies at the Specialist Centre for Kidney Cancer located at the Royal Free London NHS Foundation Trust (RFH) before and during the surge of COVID-19. RESULTS: On 18 March 2020 all elective surgery was halted at RFH to redeploy resources and staff for the COVID-19 surge. Prioritizing of patients according to European Association of Urology guidance was introduced. Clinics and the specialist multidisciplinary team (SMDT) meetings were maintained with physical distancing, kidney surgery was moved to a COVID-protected site, and infection prevention measurements were enforced. During the 7 weeks of lockdown (23 March to 10 May 2020), 234 cases were discussed at the SMDT meetings, 53% compared to the 446 cases discussed in the 7 weeks pre-lockdown. The reduction in referrals was more pronounced for small and asymptomatic renal masses. Of 62 low-priority cancer patients, 27 (43.5%) were deferred. Only one (4%) COVID-19 infection occurred postoperatively, and the patient made a full recovery. No increase in clinical or pathological upstaging could be detected in patients who underwent deferred surgery compared to pre-COVID practice. CONCLUSION: The first surge of the COVID-19 pandemic severely impacted diagnosis, referral and treatment of kidney cancer at a tertiary referral centre. With a policy of prioritization and COVID-protected pathways, capacity for time-sensitive oncological interventions was maintained and no immediate clinical harm was observed.

Challenging Cases of Renal Cell Cancers With or Without Tumor Thrombus During the Covid-19 Pandemic.

BACKGROUND/AIM: Large or bilateral multiple renal cell carcinoma (RCC) without/with tumor thrombus (TT) in the renal vein (RV) or inferior vena cava (IVC) poses a challenge to the surgeon due to the potential for massive hemorrhage, tumor thromboemboli and dialysis, and the situation is more critical due to Covid-19 pandemic. We report our experience and measures in dealing with challenging cases of large or multiple RCCs without/with TT during the ongoing Covid-19 pandemic. PATIENTS AND METHODS: Between 4/2020-10/2020, five patients underwent RCC resection with/without TT. Patients 1 and 2 had RCCs/TT in RV; Patient 3 had RCC/TT supradiaphragmatic below right atrium; Patient-4 had a 26 cm RCC; Patient-5 had multiple RCCS as part of Birt-Hogg-Dube syndrome. RESULTS: Patients were preoperatively tested negative for Covid-19. Operation times were 105, 85, 255, 200 and 247 minutes for Patients 1-5. Estimated blood loss was: 100, 50, 3,900,100 and 50 ml, respectively. Patient 3 underwent RCC resection en bloc with IVC/TT. Patients 1 and 2 underwent resections of RCC/TT in RV. Patient 4 underwent a 26 cm RCC resection. Patient 5 underwent laparoscopic bilateral radical nephrectomies. No immediate postoperative complications were reported. CONCLUSION: We successfully managed 5 challenging cases of RCCs despite the recommendations imposed by hospitals due to Covid-19 pandemic, with favorable outcomes.

Delaying surgery for clinical T1b-T2bN0M0 renal cell carcinoma: Oncologic implications in the COVID-19 era and beyond.

PURPOSE: During COVID-19, many operating rooms were reserved exclusively for emergent cases. As a result, many elective surgeries for renal cell carcinoma (RCC) were deferred, with an unknown impact on outcomes. Since surveillance is commonplace for small renal masses, we focused on larger, organ-confined RCCs. Our primary endpoint was pT3a upstaging and our secondary endpoint was overall survival. MATERIALS AND METHODS: We retrospectively abstracted cT1b-T2bN0M0 RCC patients from the National Cancer Database, stratifying them by clinical stage and time from diagnosis to surgery. We selected only those patients who underwent surgery. Patients were grouped by having surgery within 1 month, 1-3 months, or >3 months after diagnosis. Logistic regression models measured pT3a upstaging risk. Kaplan Meier curves and Cox proportional hazards models assessed overall survival. RESULTS: A total of 29,746 patients underwent partial or radical nephrectomy. Delaying surgery >3 months after diagnosis did not confer pT3a upstaging risk among cT1b (OR = 0.90; 95% CI: 0.77-1.05, P = 0.170), cT2a (OR = 0.90; 95% CI: 0.69-1.19, P = 0.454), or cT2b (OR = 0.96; 95% CI: 0.62-1.51, P = 0.873). In all clinical stage strata, nonclear cell RCCs were significantly less likely to be upstaged (P <0.001). A sensitivity analysis, performed for delays of <1, 1-3, 3-6, and >6 months, also showed no increase in upstaging risk. CONCLUSION: Delaying surgery up to, and even beyond, 3 months does not significantly increase risk of tumor progression in clinically localized RCC. However, if deciding to delay surgery due to COVID-19, tumor histology, growth kinetics, patient comorbidities, and hospital capacity/resources, should be considered.

Association of Surgical Delay and Overall Survival in Patients With T2 Renal Masses: Implications for Critical Clinical Decision-making During the COVID-19 Pandemic.

OBJECTIVE: To test for an association between surgical delay and overall survival (OS) for patients with T2 renal masses. Many health care systems are balancing resources to manage the current COVID-19 pandemic, which may result in surgical delay for patients with large renal masses. METHODS: Using Cox proportional hazard models, we analyzed data from the National Cancer Database for patients undergoing extirpative surgery for clinical T2N0M0 renal masses between 2004 and 2015. Study outcomes were to assess for an association between surgical delay with OS and pathologic stage. RESULTS: We identified 11,848 patients who underwent extirpative surgery for clinical T2 renal masses. Compared with patients undergoing surgery within 2 months of diagnosis, we found worse OS for patients with a surgical delay of 3-4 months (hazard ratio [HR] 1.12, 95% confidence interval [CI] 1.00-1.25) or 5-6 months (HR 1.51, 95% CI 1.19-1.91). Considering only healthy patients with Charlson Comorbidity Index = 0, worse OS was associated with surgical delay of 5-6 months (HR 1.68, 95% CI 1.21-2.34, P= .002) but not 3-4 months (HR 1.08, 95% CI 0.93-1.26, P = 309). Pathologic stage (pT or pN) was not associated with surgical delay. CONCLUSION: Prolonged surgical delay (5-6 months) for patients with T2 renal tumors appears to have a negative impact on OS while shorter surgical delay (3-4 months) was not associated with worse OS in healthy patients. The data presented in this study may help patients and providers to weigh the risk of surgical delay versus the risk of iatrogenic SARS-CoV-2 exposure during resurgent waves of the COVID-19 pandemic.

Consideration in the management of renal cell carcinoma during the COVID-19 Pandemic.

INTRODUCTION: Recently the COVID-19 pandemic became the main global priority; main efforts and health infrastructures have been prioritized in favor of COVID-19 battle and the treatment of benign diseases has been postponed. Renal cell cancer (RCC) patients configure a heterogenous populations: some of them present indolent cases which can safely have postponed their treatments, others present aggressive tumors, deserving immediate care. These scenarios must be properly identified before a tailored therapeutic choice. Objectives We propose a risk- based approach for patients with RCC, to be used during this unprecedented viral infection time. MATERIALS AND METHODS: After a literature review focused in COVID-19 and current RCC treatments, we suggest therapeutic strategies of RCC in two sections: surgical approach and systemic therapy, in all stages of this malignance. RESULTS: Patients with cT1a tumors (and complex cysts, Bosniak III/IV), must be put under active surveillance and delayed intervention. cT1b-T2a/b cases must be managed by partial or radical nephrectomy, some selected T1b-T2a ((≤7cm) cases can have the surgery postponed by 60-90 days). Locally advanced tumors (≥cT3 and or N+) must be promptly resected. As possible, minimally invasive surgery and early hospital discharge are encouraged. Upfront cytoreduction, is not recommendable for low risk oligometastatic patients, which must start systemic treatment or even could be put under surveillance and delayed therapy. Intermediate and poor risk metastatic patients must start target therapy and/or immunotherapy (few good responders intermediate cases can have postponed cytoreduction). The recommendation about hereditary RCC syndromes are lacking, thus we recommend its usual care. Local or loco regional recurrence must have individualized approaches. For all cases, we suggest the application of a specific informed consent and a shared therapeutic choice. CONCLUSION: In the pandemic COVID -19 times, a tailored risk-based approach must be used for a safe management of RCC, aiming to not compromise the oncological outcomes of the patients.