Comparison of Renal Cell Cancer Surgery During the COVID-19 Pandemic with Prepandemic Period, Turkey Multicenter Study

Objective: Coronavirus disease-2019 (COVID-19) pandemic changed various priorities in health area. Many elective surgeries for renal cell cancers (RCC) have been postponed. We examined the influence of the COVID-19 pandemic on the surgical treatment of RCC in Turkey. Material(s) and Method(s): Surgically treated 457 patients for kidney tumor, from March 1, 2019 to February 28, 2021 in 9 centers in Turkey were analyzed retrospectively. Result(s): The number of surgical treatments for RCC during the COVID-19 pandemic has decreased significantly, in contrast to the same period before COVID-19. Admission symptoms were similar in these two periods (p=0.32). However, although not statistically significant, the rate of admission to hospital due to hematuria was higher during the pandemic period compared to the prepandemic period (14.4% vs 9.8%, respectively). The two study periods differed significantly in terms of the rate of metastatic RCC detected in preoperative imaging (13.1% vs 6.1%, during COVID-19 and pre-COVID-19, respectively) (p=0.01). Moreover, the study periods differed significantly in terms of time between imaging and operation [35 (2-240) vs 30 (1-210) days, during COVID-19 and pre-COVID-19, respectively] (p=0.01). However, these two periods were similar in terms of tumor size, type of surgery, and pathological stage (p>=0.05). Although the pathological stages were similar among the groups, nephrectomies due to the metastatic disease were significantly higher in the pandemic period (p=0.01). Conclusion(s): The number of RCC-related surgeries were significantly decreased during the pandemic period. However, the rate of surgery for metastatic disease has significantly increased. © Copyright 2022 by Urooncology Association Bulletin of Urooncology / Published by Galenos Yayinevi 119.

RELATIONSHIP BETWEEN VITAMIN D LEVELS AND SARS-COV-2 INFECTION IN DIALYSIS PATIENTS

BACKGROUND AND AIMS: Hypovitaminosis D is highly prevalent in patients with Chronic Kidney Disease (CKD). This is considered a consequence of a decreased renal mass and a reduction in the number of proximal tubular cells, which absorb the filtered native vitamin D and then be hydroxylated to its active form by 1α-hydroxylase. Hypovitaminosis D is defined as serum levels of 25-hydroxy-vitamin D3 lower than 30 ng/mL. The decrease in vitamin D causes bone and mineral abnormalities and can also play a role in various pathologies, such as cardiovascular disease, insulin resistance, diabetes, autoimmune diseases and infections. Clinical practice guidelines recommend treating hypovitaminosis D. The role of vitamin D in acute respiratory tract infections and other viral infections has been widely studied. It has an immunomodulatory role due to the expression of the enzyme 1α-hydroxylase by the epithelium of the respiratory tract, dendritic cells and lymphocytes, which is essential for the activation of vitamin D in the lungs. In this way, an influence is created on the lung capacity to fight infections and respond to allergic stimuli. Vitamin D has the potential to influence the severity and outcomes of COVID-19. In fact, several studies have established a consistent relationship between hypovitaminosis D and the severity of COVID-19. We have a population of dialysis patients with a tendency to hypovitaminosis D and, on the other hand, an influence of hypovitaminosis D in respiratory infections such as SARS-CoV-2 infection. Thus, we consider it interesting to study whether the incidence of hypovitaminosis D is higher in dialysis patients with SARS-CoV-2 infection than in those who do not. METHOD: An observational, analytical, ambispective, multicentre study was carried out under normal clinical practice conditions. The study subjects are patients on haemodialysis program of the province of Santa Cruz de Tenerife, in the period between January 2021 and January 2022. As variables we selected age, sex, personal history, haemodialysis time, serum levels of 25-hydroxy-vitD3, treatment with native vitamin D, presence of SARS-CoV-2 infection diagnosed by RT-PCR in nasopharyngeal swab, vaccination. The information collected is organized in a database of the SPSS Statistics v22 program. For quantitative variables, the comparison between groups is made by means of an analysis with the Student's t-test for independent samples. Qualitative variables are analyzed using the Chi-squared test or Fisher's exact test. All data were analyzed using the SPSS Statistics v22 program. The level of significance is established for a value of P < 0.05. RESULTS: A total of 60 haemodialysis patients were included, 36 men (60%) and 24 women (40%). The mean age was 64 years. The most common cause of kidney disease was diabetic nephropathy (35%). The median time on dialysis was 24.5 months. 73.3% of the patients presented hypovitaminosis D and 35% received treatment with vitamin D. 23 patients had SARS-CoV-2 infection (38.3%). 2 patients (3.3%) died of COVID-19. There were no significant differences between the two comparison groups (patients with and without SARS-CoV-2 infection) in relation to sex, age, cause of kidney disease, diabetes, time on dialysis, vitamin D intake. We also did not observe significant differences in relation to vitamin D levels or the presence of hypovitaminosis D. There are significant differences in relation to vaccination (p 0.00). 39.1% of the patients with SARS-CoV-2 infection were not vaccinated. 90% of all unvaccinated patients had SARS-CoV-2 infection. 97.3% of the uninfected patients were vaccinated. CONCLUSION: Hypovitaminosis D is very common in CKD patients on dialysis, however, despite its immunomodulatory role, we did not find a higher incidence of hypovitaminosis D in dialysis patients with SARS-CoV-2 infection. In our series, we have not found factors associated with SARS-CoV-2 infection in dialysis patients, with the exception of vaccination. Therefore, vaccination in our dialysis patients is being essential t prevent a higher number of cases of SARS-CoV-2 infection.

DON'T “MIS-C” THE CANCER: A CASE REPORT OF INCIDENTALLY DIAGNOSED WILMS TUMOR DURING ACUTE MIS-C

Background: Incidental diagnosis of malignancy during unrelated illness is challenging, both for diagnostic clarity and therapeutic decision-making. There are reported cases of incidental discovery of Wilms tumor (WT) in the setting of trauma, but there are none reported in the setting of acute inflammatory illness, such as Multisystem Inflammatory Syndrome in Children (MIS-C), and thus no guidance regarding timing of definitive therapy. Objectives: We describe a patient with MIS-C and incidentally diagnosed WT in order to inform the management of future patients with simultaneously diagnosed malignancy and acute inflammatory illness. Design/Method: Information was obtained by retrospective review of the electronic health record. Results: A healthy 5-year-old female presented with six days of fever, cervical lymphadenopathy, urinary symptoms, and rash. Labs showed acute kidney injury, prompting imaging that revealed a left-sided renal mass, most likely a WT. The constellation of signs and symptoms was initially suggestive of obstructive uropathy resulting in urinary tract infection. However, subsequent development of conjunctivitis and oral mucosal changes, positive SARS-CoV-2 nucleocapsid antibodies, rising inflammatory markers, and mild-moderate coronary artery dilation on echocardiogram, made MIS-C the most fitting diagnosis. The patient rapidly improved after initiation of aspirin, methylprednisolone, and intravenous immunoglobulin. Cross-sectional imaging showed no metastatic disease or local tumor invasion. A multidisciplinary team of pediatric subspecialists discussed appropriate timing for upfront resection and decided to defer surgery for at least two weeks while inflammation resolved. Unfortunately, the patient continued to have ongoing inflammation requiring a prolonged steroid course, and surgery was ultimately deferred until one month following diagnosis. Surgery was uncomplicated and pathology demonstrated stage II favorable histology WT. Chemotherapy began on post-operative day 9. Conclusion: The lack of published cases of malignancy incidentally discovered during acute illness, coupled with the rapidly rising rate of pediatric cases of COVID-19 and MIS-C, present a challenge for clinicians who must treat the concurrent conditions. This report highlights the complexities of managing a WT for which upfront resection is standard in the United States. Surgery is typically performed quickly due to the fast-growing nature and risk of rupture. Reports of paraneoplastic inflammatory syndromes (non-WT) suggest that tumor resection in the setting of acute inflammation is safe, but pediatric data remains scarce. This patient's multidisciplinary team chose to delay tumor resection given the potential morbidity of major surgery in the setting of a raging inflammatory state. The patient had a favorable clinical outcome both in terms of her MIS-C and WT.

A Rare Case of Intussusception in A COVID-19 Positive Patient with Nephrotic Syndrome

Background and Objective: Intussusception is one of the most common causes of intestinal obstruction in children 5 months to 3 years, which is the most common cause of acute abdominal pain and its prevalence increases as a result of viral infection. In this report, were present a case of intussusception in a 17-years-old boy following COVID-19. Case Report: A 17-year-old adolescent boy with a known case of steroid-dependent nephrotic syndrome from the age of two has been referred to the emergency department with severe abdominal pain and vomiting. On ultrasound, renal mass and free fluids were shown. Ileocecal intussusception was observed and was repaired without any complications. Conclusion: Based on the results of this study, intussusception should be considered in every patient with nephrotic syndrome with COVID-19 infection.

Phase 2 study of neoadjuvant cabozantinib in patients with locally advanced non-metastatic clear cell renal cell carcinoma

Background: Cabozantinib is a small molecule inhibitor of the tyrosine kinases c-Met, AXL and VEGFR2 that has been shown to reduce tumor growth, metastasis, and angiogenesis. After the promising results from the METEOR, CABOSUN and Checkmate-9ER trials, cabozantinib was approved for use in patients with advanced renal cell carcinoma (RCC). The increased response rates with cabozantinib in metastatic RCC, along with the other neoadjuvant TKI data, support an expanded role for cabozantinib in the neoadjuvant setting. Methods: Patients with clinical stage ≥ T3Nx or TanyN+ or deemed unresectable by the surgeon with biopsy-proven clear cell RCC were eligible for this study, and received cabozantinib at a starting dose of 60 mg daily for 12 weeks. The primary outcome was objective response rate per RECIST v1.1 (complete and partial responses) at week 12 after the administration of cabozantinib as determined by independent radiologist review. Secondary outcomes included safety, tolerability, clinical outcome (DFS, OS), surgical outcome and quality of life. Results: As of 20 September 2021, 16 biopsy-proven clear cell RCC patients were treated with neoadjuvant cabozantinib. The median age was 56 years (range: 41-84 years) and 81.2% male. All patients completed 12 weeks of treatment, and 15 of them underwent surgery as planned without any delay after completion of 4 weeks wash-out. One patient refused to undergo surgery due to personal reasons and received further systemic treatment. Five patients (31.2%) experienced a partial response, and 11 patients had stable disease. There was no progression of disease while on cabozantinib. Median reduction of primary renal tumor size was 24% (range: 6-45%). The one patient who was deemed to be unresectable became resectable at the end of treatment. Two patients were converted from radical to partial nephrectomy. The most common AEs were diarrhea, nausea, fatigue, hypertension, anorexia, and palmar-plantar erythrodysesthesia syndrome. Intraoperatively, we did not experience any immediate complications. Postoperatively, no surgical complications related to the drug were noted. No treatment related grade 4 or 5 AEs related to cabozantinib or surgery occurred. Two patients had died at the time of analysis (1 due to COVID and 1 unknown cause). Conclusions: Cabozantinib was clinically active and safe in the neoadjuvant setting in patients with locally advanced non-metastatic clear cell RCC. Additional data will be reported including long term outcomes, correlative studies, quality of life, and frailty/sarcopenia indices.

European Association of Urology COVID intermediate prioritisation group is poorly predictive of pathological high-risk among patients with renal tumours

Introduction & Objectives: The purpose of prioritisation is to minimise harm while safeguarding access to health care in times of reduced clinical resources. The EAU Guideline Office Rapid Reaction Group (GORRG) issued priority recommendations for use during the COVID-19 pandemic. We evaluated if the clinical prioritisation for suspected renal cell carcinoma (RCC) planned for surgery matched final pathological risk. Materials & Methods: From 23 March 2020 at the beginning of the first lock-down in the UK, patients with suspected RCC were prioritised according to GORRG recommendations until 10 October 2020. To increase statistical power, GORRG prioritisation was also retrospectively assigned to pre-lockdown RCC surgical cases, dating back to April 5 2019. Patient and tumour characteristics were assessed, as was priority group according to GORRG, TNM, and postoperative risk according to 2003 Leibovich scores. We assessed concordance between pre-operative GORGG prioritisation group and post-operative risk, and if stratification could be further improved by subgrouping of size. Results: 351 patients with suspected RCC were prioritised and underwent surgery, of which 16 were benign and 335 were RCC after specimen analysis. The intermediate priority group did not match the pathological risk group in 47.7%, with 25.7% and 16.4% of the group being pathological low and high risk, respectively. The low GORRG priority group harboured 14.9% intermediate and 1.06% high risk RCC, and the high GORRG priority group 27.9% intermediate and no low risk RCC respectively. Within the GORRG intermediate group, 34.2% of cT1b tumours were low risk, and 32.3% of cT2a tumours high risk. Analysing at 1 cm increments, 45.1% of 4-5cm tumours were low risk. The area under the receiver operating characteristics curve for priority groups in predicting matched postoperative risk group was 0.60 (95% CI 0.55-0.65). The sankey diagram shows patients categorised according to EAU GORGG guidelines (left) and pathological risk (right).(Figure Presented)Conclusions: The recommended prioritisation system can be error prone and should be prudently applied based on the centre’s needs. Particularly amongst the intermediate group, centres with clinical capacity should not defer intervention of cT2a tumours for longer than absolutely necessary and in severely limited resources may consider intermediate priority tumours <5cm as low priority.

Exploring the diversity and predictors of histopathological findings across the European Association of Urology Guidelines Office rapid reaction group priority groups for patients with renal tumours: Implications for prioritization of renal cancer care

Introduction & Objectives: The COVID-19 pandemic has forced disruptive changes in the prioritization of care in Urology worldwide. In response to the first peak of the outbreak, the European Association of Urology (EAU) Guidelines Office Rapid Reaction Group (GORRG) provided comprehensive recommendations to guide the prioritization of surgery for patients with non-metastatic renal cell carcinoma (RCC). Notably, to date, such priority groups have not been validated from a histopathological perspective. To fill this gap, in this study we sought to explore the diversity and predictors of histopathological findings across the EAU GORRG priority groups for renal tumors at a referral Academic Centre. Materials & Methods: After Ethical Committee approval, we queried our prospectively collected Institutional database to select consecutive patients undergoing elective surgery for cT1-4 N0-1 M0 renal masses between January 2017 and December 2020. The primary outcome measures at histopathological analysis were: a) benign histology;b) non-organ confined disease (pT3-4 and/or pN1);c) adverse pathologic features for both clear cell RCC (ccRCC) and papillary RCC (pRCC) according to validated prognostic models. Results: Overall, 940 (54.2%), 358 (20.6%) and 436 (25.2%) patients were classified as low-, intermediate- and high-priority, respectively. The three groups significantly differed regarding all primary histopathological outcomes: benign histology (21.6% vs 15.9% vs 6.4% for the low-, intermediate- and high-risk group, respectively, p<0.001);b) non-organ-confined disease (5.0% vs 19.0% vs 45.4%, p<0.001);c) adverse pathologic features according to validated prognostic models (including median Leibovich score for clear cell RCC: 0 vs 2 vs 4, p<0.001). At multivariable analysis, beyond the EAU GORRG priority groups, specific patient and/or tumor-related characteristics were independent predictors of the aforementioned histopathological outcomes. s EAU22 – 37th Annual EAU Congress (Figure Presented) Conclusions: To the best of our knowledge, our study showed for the first time the value of the EAU GORRG priority groups from a histopathological standpoint, prompting the implementation of such a prioritization scheme beyond the COVID-19 pandemic.

COVID-19 pneumonia in a child. A surprise finding

Background: Coronavirus disease 19 (COVID-19) tends to be milder in children, but severe cases have been reported. We described a case report of a toddler admitted to our department with additional findings, highlighting the importance of assessing the patient as a whole. Case Presentation: A previously healthy, 15-month-year-old girl presented with fever and dry cough for 10 days, respiratory distress and PCR SARS-CoV-2 was positive. At admission, she presented with hypoxemia (SpO2 89-90% in room air), global retraction and bilateral bronchospasm. She was treated with bronchodilators, methylprednisolone, remdesivir and also amoxicillin/clavulanic acid. Her complete blood count revealed leucocytosis 16,160x109/L, 41% lymphocytes, C-reactive protein 57,9 mg/L, procalcitonin 0,13 ng/mL, sedimentation rate 44 mm/h, ferritin 218,4 ng/mL. Chest computed tomography (CT) scan revealed bilateral peripheral areas of ground glass, coexisting consolidation areas at inferior lobes but also revealed a 6 cm supra-renal mass. Abdominal ultrasound and CT confirmed an heterogeneous right supra-renal gland mass of 5,5cm along the greatest diameter with diffuse calcifications, evolving the inferior vena cava and the renal vascular pedicle, no signs of liver, bone, cutaneous or ganglionic metastization. These features were suggestive of neuroblastoma in stage L2. Vanillylmandelic acid, normetanephrine/creatinine ratio and metanephrine/creatinine ratio were elevated. The metaiodobenzylguanidine (Mibg) scan showed a localized disease. The total excision of the tumour mass was performed, and the histology confirmed neuroblastoma with no N-myc oncogene amplification, nor other bad prognosis chromosomal abnormalities. She is currently under oncological surveillance, with no signs of recurrence. Learning Points Discussion: Neuroblastoma is the most common extracranial solid tumour of childhood. It is known for its broad spectrum of clinical behaviour and outcome. In this case, although this toddler was admitted due to COVID-19 pneumonia, it allowed to identify a localized tumour, perform excision and due to the favourable biology tumour, she has a very good chances of being cured and free of disease.

Diagnostic bias during the COVID-19 era: COVID-19 or renal abscess?

INTRODUCTION: The Coronavirus disease-2019 (COVID-19) has been declared as a pandemic in March 2020 by the World Health Organization (WHO). Since then, this pandemic has dramatically affected the entire world, even radically influencing the way patients are framed at triage. Symptoms and tests in most cases lead to a correct diagnosis; however, error may be around the corner. CASE REPORT: A 60 years old patient was referred with weight loss, fatigue and mild fever for 3 weeks as he was working in a COVID-19 ward. After a positive swab and chest CT scan, he was admitted in the hospital and treated as mild COVID-19 patient. A CT scan performed after the patient was discharged revealed a renal lesion misidentified as a tumor then clarified to be an abscess which retrospectively appears to be the main cause of his symptoms. CONCLUSION: Clinicians should consider other life-threatening disease in the differential diagnosis of patients presenting with similar symptoms to minimize mistakes and avoid further unnecessary investigations.