Publications by authors named "Anil Kapoor"

289 Publications

Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma.

N Engl J Med 2021 Feb 13. Epub 2021 Feb 13.

From Memorial Sloan Kettering Cancer Center, New York (R.M.); P. Hertsen Moscow Oncology Research Institute, Moscow (B.A.), the State Institution of Health Care Regional Clinical Oncology Dispensary, Omsk (E.K.), the State Budgetary Health Care Institution Novosibirsk Regional Clinical Oncology Dispensary, Novosibirsk (V.K.), and Prevoljskiy Region Medical Center, Novgorod (A.A.) - all in Russia; Yonsei Cancer Center, Yonsei University Health System (S.Y.R.), Seoul St. Mary's Hospital, Catholic University of Korea (S.-H.H.), and Seoul National University Hospital (M.K.), Seoul, South Korea; San Matteo University Hospital Foundation, Pavia (C.P.), Istituto Nazionale dei Tumori IRCCS, Milan (G.P.), and Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRCCS, Meldola (U.D.G.) - all in Italy; Kyushu University, Fukuoka (M.E.), and Tokyo Women's Medical University, Tokyo (T.T.) - both in Japan; the Royal Free NHS Trust, London (T.P.), and Eisai, Hatfield (A.D.S.) - both in the United Kingdom; University Hospital Essen, Essen (V.G.), and the University of Tübingen, Tübingen (J.B.) - both in Germany; Texas Oncology, Dallas (T.E.H.); Maimonides Institute for Biomedical Research of Cordoba Hospital Universitario Reina Sofía, Medical Oncology Department, Córdoba (M.J.M.-V.), Hospital Universitario Ramón y Cajal, Madrid (T.A.G.), and Hospital de la Santa Creu i Sant Pau, Barcelona (P.M.) - all in Spain; McMaster University, Hamilton (A.K.), and Western University, London (E.W.) - both in Ontario, Canada; the University of Miami Sylvester Comprehensive Cancer Center, Miami (J.R.M.), and Florida Cancer Specialists, Gainesville (V.P.); ICON Research, South Brisbane, and University of Queensland, St. Lucia, QLD (J.C.G.), Macquarie University, Sydney (H.G.), and Western Health, Melbourne, VIC (S.W.) - all in Australia; Rambam Health Care Campus, Haifa, Israel (A.P.); Palacky University and University Hospital Olomouc, Olomouc, Czech Republic (B.M.); Centre René Gauducheau, Saint Herblain, France (F.R.); the Department of Urology, Medical University of Vienna, Vienna (M.S.); Eisai, Woodcliff Lake (C.E.D., L.D., K.M., D.X.), and Merck, Kenilworth (R.F.P.) - both in New Jersey; and Dana-Farber Cancer Institute, Boston (T.K.C.).

Background: Lenvatinib in combination with pembrolizumab or everolimus has activity against advanced renal cell carcinoma. The efficacy of these regimens as compared with that of sunitinib is unclear.

Methods: In this phase 3 trial, we randomly assigned (in a 1:1:1 ratio) patients with advanced renal cell carcinoma and no previous systemic therapy to receive lenvatinib (20 mg orally once daily) plus pembrolizumab (200 mg intravenously once every 3 weeks), lenvatinib (18 mg orally once daily) plus everolimus (5 mg orally once daily), or sunitinib (50 mg orally once daily, alternating 4 weeks receiving treatment and 2 weeks without treatment). The primary end point was progression-free survival, as assessed by an independent review committee in accordance with Response Evaluation Criteria in Solid Tumors, version 1.1. Overall survival and safety were also evaluated.

Results: A total of 1069 patients were randomly assigned to receive lenvatinib plus pembrolizumab (355 patients), lenvatinib plus everolimus (357), or sunitinib (357). Progression-free survival was longer with lenvatinib plus pembrolizumab than with sunitinib (median, 23.9 vs. 9.2 months; hazard ratio for disease progression or death, 0.39; 95% confidence interval [CI], 0.32 to 0.49; P<0.001) and was longer with lenvatinib plus everolimus than with sunitinib (median, 14.7 vs. 9.2 months; hazard ratio, 0.65; 95% CI, 0.53 to 0.80; P<0.001). Overall survival was longer with lenvatinib plus pembrolizumab than with sunitinib (hazard ratio for death, 0.66; 95% CI, 0.49 to 0.88; P = 0.005) but was not longer with lenvatinib plus everolimus than with sunitinib (hazard ratio, 1.15; 95% CI, 0.88 to 1.50; P = 0.30). Grade 3 or higher adverse events emerged or worsened during treatment in 82.4% of the patients who received lenvatinib plus pembrolizumab, 83.1% of those who received lenvatinib plus everolimus, and 71.8% of those who received sunitinib. Grade 3 or higher adverse events occurring in at least 10% of the patients in any group included hypertension, diarrhea, and elevated lipase levels.

Conclusions: Lenvatinib plus pembrolizumab was associated with significantly longer progression-free survival and overall survival than sunitinib. (Funded by Eisai and Merck Sharp and Dohme; CLEAR ClinicalTrials.gov number, NCT02811861.).
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http://dx.doi.org/10.1056/NEJMoa2035716DOI Listing
February 2021

Prospective, Single-Arm Trial Evaluating Changes in Uptake Patterns on Prostate-Specific Membrane Antigen (PSMA)-Targeted F-DCFPyL PET/CT in Patients with Castration-Resistant Prostate Cancer Starting Abiraterone or Enzalutamide.

J Nucl Med 2021 Feb 19. Epub 2021 Feb 19.

Johns Hopkins University School of Medicine, United States.

Positron emission tomography (PET) with small molecules targeting prostate-specific membrane antigen (PSMA) is being adopted as a clinical standard for prostate cancer (PCa) imaging. In this study, we evaluated changes in uptake on PSMA-targeted PET in men starting abiraterone or enzalutamide. This prospective, single-arm, two-center, exploratory clinical trial enrolled men with metastatic castration-resistant prostate cancer (CRPC) initiating abiraterone or enzalutamide. Each patient was imaged with F-DCFPyL at baseline and within 2-4 months after starting therapy. Patients were followed for up to 48 months from enrollment. A central review evaluated baseline and follow-up PET scans recording change in maximum standardized uptake value (SUV) at all disease sites and classifying the pattern of change. Two parameters: the delta percent SUV (DPSM) of all lesions and the delta absolute SUV (DASM) of all lesions were derived. Kaplan-Meier curves were used to estimate time to therapy change (TTTC) and overall survival (OS). Sixteen evaluable patients were accrued to the study. Median TTTC was 9.6 months (95% confidence interval (CI), 6.9-14.2) and median OS was 28.6 months (95% CI 18.3-not available (N/A)). Patients with a mixed-but-predominantly-increased pattern of radiotracer uptake had shorter TTTC and OS. Men with low DPSM had median TTTC 12.2 months (95% CI 11.3-N/A) and median OS 37.2 months (95% CI 28.9-N/A), while those with high DPSM had median TTTC 6.5 months (95% CI 4.6-N/A, = 0.0001) and median OS 17.8 months (95% CI 13.9-N/A, = 0.02). Men with low DASM had median TTTC 12.2 months (95% CI 11.3-N/A) and median OS N/A (95% CI 37.2 months-N/A), while those with high DASM had median TTTC 6.9 months (95% CI 6.1-N/A, = 0.003) and median OS 17.8 months (95% CI 13.9-N/A, = 0.002). Findings on PSMA-targeted PET 2-4 months after initiation of abiraterone or enzalutamide are associated with TTTC and OS. Development of new lesions and/or increasing intensity of radiotracer uptake at sites of baseline disease are poor prognostic findings suggesting shorter TTTC and OS.
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http://dx.doi.org/10.2967/jnumed.120.259069DOI Listing
February 2021

Comparison between small renal masses 0-2 cm vs. 2.1-4 cm in size: A population-based study.

Urol Oncol 2021 Feb 15. Epub 2021 Feb 15.

Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, Quebec, Canada; Division of Urology, University of Montreal Hospital Center (CHUM), Montreal, Quebec, Canada.

Background: The NCCN guidelines recommend active surveillance (AS) as an option for the initial management of cT1a 0-2 cm renal lesions. However, data about comparison between renal cell carcinoma (RCC) 0-2 cm vs. 2.1-4 cm are scarce.

Methods: Within the Surveillance, Epidemiology, and End Results database (2002-2016), 46,630 T1a NM stage patients treated with nephrectomy were identified. Data were tabulated according to histological subtype, tumor grade (low [LG] vs. high [HG]), as well as age category and gender. Additionally, rates of synchronous metastases were quantified.

Results: Overall, 69.3 vs. 74.1% clear cell, 21.4 vs. 17.6% papillary, 6.9 vs. 6.8% chromophobe, 2.0 vs. 1.1% sarcomatoid dedifferentiation, 0.2 vs. 0.2% collecting duct histological subtype were identified for respectively 0-2 cm and 2.1-4 cm RCCs. In both groups, advanced age was associated with higher rate of HG clear cell and HG papillary histological subtype. In 0-2 cm vs. 2.1-4 cm RCCs, 13.8% vs. 20.2% individuals operated on harbored HG tumors and were more prevalent in males. Lower synchronous metastases rates were recorded in 0-2 cm RCC and ranged from 0 in respectively multilocular cystic to 0.9% in HG papillary histological subtype. The highest synchronous metastases rates were recorded in sarcomatoid dedifferentiation histological subtype (13.8% and 9.7%) in both groups.

Conclusions: Relative to 2.1-4 cm RCCs, 0-2 cm RCCs harbored lower rates of HG tumors, lower rates of aggressive variant histology and lower rates of synchronous metastases. The indications and demographics of patients selected for AS may be expanded in the future to include younger and healthier patients.
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http://dx.doi.org/10.1016/j.urolonc.2021.01.003DOI Listing
February 2021

Differential Expression of a Panel of Ten CNTN1-Associated Genes during Prostate Cancer Progression and the Predictive Properties of the Panel Towards Prostate Cancer Relapse.

Genes (Basel) 2021 Feb 10;12(2). Epub 2021 Feb 10.

Department of Surgery, McMaster University, Hamilton, ON L8S 4K1, Canada.

Contactin 1 (CNTN1) is a new oncogenic protein of prostate cancer (PC); its impact on PC remains incompletely understood. We observed CNTN1 upregulation in LNCaP cell-derived castration-resistant PCs (CRPC) and CNTN1-mediated enhancement of LNCaP cell proliferation. CNTN1 overexpression in LNCaP cells resulted in enrichment of the CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_3 gene set that facilitates endocrine resistance in breast cancer. The leading-edge (LE) genes ( = 10) of this enrichment consist of four genes with limited knowledge on PC and six genes novel to PC. These LE genes display differential expression during PC initiation, metastatic progression, and CRPC development, and they predict PC relapse following curative therapies at hazard ratio (HR) 2.72, 95% confidence interval (CI) 1.96-3.77, and = 1.77 × 10 in The Cancer Genome Atlas (TCGA) PanCancer cohort ( = 492) and HR 2.72, 95% CI 1.84-4.01, and = 4.99 × 10 in Memorial Sloan Kettering Cancer Center (MSKCC) cohort ( = 140). The LE gene panel classifies high-, moderate-, and low-risk of PC relapse in both cohorts. Additionally, the gene panel robustly predicts poor overall survival in clear cell renal cell carcinoma (ccRCC, = 1.13 × 10), consistent with ccRCC and PC both being urogenital cancers. Collectively, we report multiple CNTN1-related genes relevant to PC and their biomarker values in predicting PC relapse.
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http://dx.doi.org/10.3390/genes12020257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916715PMC
February 2021

Utilization of Salvage and Systemic Therapies for Recurrent Prostate Cancer as a Result of F-DCFPyL PET/CT Restaging.

Adv Radiat Oncol 2021 Jan-Feb;6(1):100553. Epub 2020 Sep 9.

Department of Oncology, Division of Radiation Oncology, London Health Sciences Centre and Western University, London, Canada.

Purpose: Our purpose was to investigate the effect of the addition of prostate-specific membrane antigen (PSMA)-targeted positron emission tomography/computed tomography (PET/CT) in patients with recurrent prostate cancer post-primary radiation therapy.

Methods And Materials: A prospective, multi-institutional clinical trial evaluated 2-(3-{1-carboxy-5-[(6-[18F]fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (F-DCFPyL) PET/CT restaging in 79 men with recurrent prostate cancer post-primary radiation therapy. We report actual patient management and compare this with proposed management both before and after PSMA-targeted PET/CT.

Results: Most patients (59%) had a major change in actual management compared with pre-PET/CT proposed management. The rate of major change was underestimated by immediately post-PET/CT surveys (32%). Eighteen patients with PSMA avidity in the prostate gland suspicious for malignancy had a prostate biopsy. Sensitivity, specificity, and positive predictive values of PSMA uptake in the prostate were 86%, 67%, and 92%, respectively. Thirty percent of patients had directed salvage therapy and 41% underwent systemic therapy. Eleven out of 79 patients (14%) had high-dose-rate brachytherapy alone for local recurrence, and 91% were free of recurrence at a median follow-up of 20 months.

Conclusions: Most patients had a major change in actual management compared with pre-PSMA-targeted PET/CT planned management, and this was underestimated by post-PET/CT questionnaires.
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http://dx.doi.org/10.1016/j.adro.2020.08.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820022PMC
September 2020

The impact of sex and age on distribution of metastases in patients with renal cell carcinoma.

Int J Clin Oncol 2021 Jan 30. Epub 2021 Jan 30.

Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montreal Health Center, Montreal, QC, Canada.

Background: Our objective was to investigate age and sex-related discrepancies on distribution of metastases in patients with metastatic renal cell carcinoma (RCC).

Methods: Within the National Inpatient Sample database (2008-2015) we identified 9607 patients with metastatic RCC. Trend test and Chi-square test analyses were used to evaluate the relationship between age and site of metastases, according to sex.

Results: Of 9607 patients with metastatic RCC, 6344 (65.9%) were men and 3263 (34.1%) were women. Thoracic, abdominal, bone and brain metastases were present in 51.1 vs. 52.8%, 42.6 vs. 44.3%, 29.9 vs. 29.2% and 8.6 vs. 8.8% of men vs. women, respectively. Increasing age was associated with decreasing rates of thoracic (from 55.5 to 48.5%) and brain (from 8.6 to 5.8%) metastases in men and with decreasing rates of abdominal (from 48.3 to 39.6%), bone (from 32.6 to 24.9%) and brain (from 8.8 to 5.4%) metastases in women. (all p < 0.05). Rates of concomitant metastatic sites also decreased with increasing age, from 57.1 to 50.8% in men and from 54.1 to 50.2% in women.

Conclusions: Important age and sex-related differences exist in the distribution of RCC metastases. The distribution of metastases is marginally different between sexes. Specifically, more advanced age is associated with lower rates of thoracic and brain metastases in men and with lower rates of abdominal, bone and brain metastases in women. Age and sex should be take into consideration into the staging management strategy, as well as into the follow-up strategy of patients with metastatic RCC.
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http://dx.doi.org/10.1007/s10147-021-01874-3DOI Listing
January 2021

Effective Prediction of Prostate Cancer Recurrence through the Network.

Cancers (Basel) 2021 Jan 23;13(3). Epub 2021 Jan 23.

Department of Medicine, McMaster University, Hamilton, ON L8S 4L8, Canada.

IQGAP1 expression was analyzed in: (1) primary prostate cancer, (2) xenografts produced from LNCaP, DU145, and PC3 cells, 3) tumor of and TRAMP mice, and (3) castration resistant PC (CRPC) produced by LNCaP xenografts and mice. IQGAP1 downregulations occurred in CRPC and advanced PCs. The downregulations were associated with rapid PC recurrence in the TCGA PanCancer ( = 492, = 0.01) and MSKCC ( = 140, = 4 × 10) cohorts. Differentially expressed genes ( = 598) relative to IQGAP1 downregulation were identified with enrichment in chemotaxis, cytokine signaling, and others along with reductions in immune responses. A novel 27-gene signature (Sig27gene) was constructed from these DEGs through random division of the TCGA cohort into a Training and Testing population. The panel was validated using an independent MSKCC cohort. Sig27gene robustly predicts PC recurrence at (hazard ratio) HR 2.72 and p < 2 × 10 in two independent PC cohorts. The prediction remains significant after adjusting for multiple clinical features. The novel and robust nature of Sig27gene underlie its great translational potential as a prognostic biomarker to predict PC relapse risk in patients with primary PC.
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http://dx.doi.org/10.3390/cancers13030430DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865788PMC
January 2021

Vitamin D deficiency in athletes and its impact on outcome of Anterior Cruciate Ligament surgery.

Eur J Orthop Surg Traumatol 2021 Jan 8. Epub 2021 Jan 8.

Department of Orthopaedics, Government Medical College and Hospital, Chandigarh, India.

Background: Vitamin D deficiency is a worldwide pandemic problem. With vitamin D having some role in exercise-induced inflammation, skeletal muscle mass and endurance, we studied its effect on functional outcome of athletes' post-Anterior Cruciate Ligament (ACL) reconstruction.

Methods: A total of 153 patients who underwent primary ACL reconstruction were enrolled in the study. All patients were screened for vitamin D levels preoperatively. Patients were divided into 3 groups on basis of vitamin D levels; Group 1 patients had < 20 ng/ml, group 2 patients 20-30 ng/ml and group 3 > 30 ng/ml. All patients were followed up for a minimum of 2 years.

Results: A total of 153 patients were enrolled in study. The average age of the patients was 24.12 ± 2.12 years in group 1, 25.24 ± 3.20 years in group 2 and 24.74 ± 2.86 in group 3. The mean follow-up of patients was 2.8 ± 1.2 years. At 2 years, the mean Lysholm score was 96.12, 96.49 and 97.0, respectively (p = 0.75); mean WOMAC score was 3.33, 3.38 and 3.20, respectively (p = 0.91); mean difference between the pre-injury and post-surgery Tegner level of sports activity at 2 years follow-up was 0.78, 0.78 and 0.85, respectively (P = 0.51) and graft failure rate was 5.88%, 1.96% and 1.96%, respectively (p = 0.43).

Conclusion: Vitamin D has no effect on functional outcome and graft rupture rates in patients' post-primary ACL reconstruction.

Level Of Evidence: Prospective Cohort Study (Level III).
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http://dx.doi.org/10.1007/s00590-020-02870-5DOI Listing
January 2021

Hypothermia During Partial Nephrectomy for Patients with Renal Tumors: A Randomized Controlled Trial.

J Urol 2020 Dec 21:101097JU0000000000001517. Epub 2020 Dec 21.

Division of Urology, Department of Surgery, The Ottawa Hospital, Ottawa, Ontario, Canada.

Background: Surgeons induce renal hypothermia during partial nephrectomy to preserve kidney function, without strong evidence of benefit. This trial examined the effectiveness and safety of renal hypothermia during partial nephrectomy.

Methods: We conducted a parallel randomized controlled trial of hypothermia versus no hypothermia (control group) during partial nephrectomy at six academic hospitals. Eligible patients had a planned open partial nephrectomy for the treatment of a renal tumor. During surgery, after clamping the renal hilum, patients were randomized to the intervention or control arm in a 1:1 ratio using permuted blocks of variable lengths (2 and 4), stratified by institution, using a computer-based program. Surgeons and study coordinators were masked to treatment allocation until the renal hilum was clamped. Overall glomerular filtration rates were determined before, and 1-year after, surgery. The primary outcome was measured glomerular filtration rate (mGFR) assessed by the plasma clearance of Tc-DTPA. The trial (NCT01529658) was designed with 90% power to detect a minimal clinically important difference in mGFR of 10ml/min/1.73m at a 5% significance level.

Findings: Of the 184 patients randomized, hypothermia and control patients had similar baseline mean mGFR (87.1 vs 81.0 ml/min/1.73m). One hundred and sixty-one (79 hypothermia, 82 control) were alive with primary outcome data 1-year after surgery. The change in mGFR 1-year after surgery was -6.6 ml/min/1.73m in the hypothermia group and -7.8 mL/min/1.73m in the control group (mean difference 1.2 mL/min/1.73m, 95% CI -3.3 to 5.6). Operated-kidney change in mGFR was similar between groups (-5.8 vs -6.3 mL/min/1.73m; mean difference 0.5 mL/min/1.73m, 95% CI -2.9 to 3.8). No clinically significant difference in the mGFR was observed when patients were stratified by pre-planned subgroups. Renal hypothermia did not impact the secondary outcomes of surgical complications and patient reported quality of life.

Interpretation: Renal hypothermia during partial nephrectomy does not preserve kidney function in patients with normal or mildly impaired renal function.
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http://dx.doi.org/10.1097/JU.0000000000001517DOI Listing
December 2020

Determining generalizability of the Canadian Kidney Cancer information system (CKCis) to the entire Canadian kidney cancer population.

Can Urol Assoc J 2020 Oct;14(10):E499-E506

Department of Medicine and Urology, Dalhousie University, Halifax, NS, Canada.

Introduction: The Canadian Kidney Cancer information system (CKCis) has prospectively collected data on patients with renal tumors since January 1, 2011 from 16 sites within 14 academic centers in six provinces. Canadian kidney cancer experts have used CKCis data to address several research questions. The goal of this study was to determine if the CKCis cohort is representative of the entire Canadian kidney cancer population, specifically regarding demographic and geographic distributions.

Methods: The CKCis prospective cohort was analyzed up to December 31, 2018. Baseline demographics and tumor characteristics were analyzed, including location of patients' residence at the time of CKCis entry. Geographic data is presented by province, rural vs. urban via postal code information (2 digit=0) and by Canadian urban boundary files. To determine the proportion of renal cell carcinoma (RCC) patients that CKCis captures, CKCis accruals were compared to projected Canadian Cancer Society RCC incidence in 2016-2017 and the incidence from the 2016 Canadian Cancer Registry. To determine if the CKCis baseline data is representative, it was compared to registry data and other published data when registry data was not available.

Results: This CKCis cohort includes 10 298 eligible patients: 66.6% male, median age 62.6 years; 14.6% had metastatic disease at the time of diagnosis and 70.4% had clear-cell carcinomas. The CKCis cohort captures about 1250 patients per year, which represents approximately 20% of the total kidney cancer incidence. The proportion of patients captured per province did vary from 13-43%. Rural patients make up 17% of patients, with some baseline differences between rural and urban patients. There appears to be no major differences between CKCis patient demographics and disease characteristics compared to national data sources. Canadian heat maps detailing patient location are presented.

Conclusions: CKCis contains prospective data on >10 000 Canadian kidney cancer patients, making it a valuable resource for kidney cancer research. The baseline demographic and geographic data do appear to include a broad cross-section of patients and seem to be highly representative of the Canadian kidney cancer population. Moving forward, future projects will include determining if CKCis cancer outcomes are also representative of the entire Canadian kidney cancer population and studying variations across provinces and within rural vs. urban areas.
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http://dx.doi.org/10.5489/cuaj.6716DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716824PMC
October 2020

Construction of a Novel Multigene Panel Potently Predicting Poor Prognosis in Patients with Clear Cell Renal Cell Carcinoma.

Cancers (Basel) 2020 Nov 22;12(11). Epub 2020 Nov 22.

Department of Medicine, McMaster University, Hamilton, ON L8S 4L8, Canada.

We observed associations of IQGAP1 downregulation with poor overall survival (OS) in clear cell renal cell carcinoma (ccRCC). Differentially expressed genes (DEGs, = 611) were derived from ccRCCs with ( = 111) and without IQGAP1 ( = 397) reduction using the TCGA PanCancer Atlas ccRCC dataset. These DEGs exhibit downregulations of immune response and upregulations of DNA damage repair pathways. Through randomization of the TCGA dataset into a training and testing subpopulation, a 9-gene panel (SigIQGAP1NW) was derived; it predicts poor OS in training, testing, and the full population at a hazard ratio (HR) 2.718, < 2 × 10, = 1.08 × 10, and < 2 × 10, respectively. SigIQGAP1NW independently associates with poor OS (HR 1.80, = 2.85 × 10) after adjusting for a set of clinical features, and it discriminates ccRCC mortality at time-dependent AUC values of 70% at 13.8 months, 69%/31M, 69%/49M, and 75.3%/71M. All nine component genes of SigIQGAP1NW are novel to ccRCC. The inclusion of RECQL4 (a DNA helicase) in SigIQGAP1NW agrees with IQGAP1 DEGs enhancing DNA repair. THSD7A affects kidney function; its presence in SigIQGAP1NW is consistent with our observed THSD7A downregulation in ccRCC ( = 523) compared to non-tumor kidney tissues ( = 100). Collectively, we report a novel multigene panel that robustly predicts poor OS in ccRCC.
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http://dx.doi.org/10.3390/cancers12113471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700485PMC
November 2020

Canadian Urological Association best practice report: Diagnosis and management of sporadic angiomyolipomas.

Can Urol Assoc J 2020 Nov;14(11):E527-E536

Division of Urology, Department of Surgery, Trillium Health Partners, Mississauga, ON, Canada.

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http://dx.doi.org/10.5489/cuaj.6942DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673831PMC
November 2020

Combined Anterior Pelvic (CAP) approach for fracture acetabulum fixation - Functional outcome evaluation and predictors of outcome.

J Clin Orthop Trauma 2020 Nov-Dec;11(6):1136-1142. Epub 2020 Oct 14.

Department of Orthopaedics Max Multi-speciality Hospital Mohali, 160062, India.

Objective: Ilio-inguinal approach has been considered standard anterior approach for acetabulum fracture fixation. Different modifications of this approach have been described. This study analysed the patients treated using a Combined Anterior Pelvic (CAP) approach - minimal AIP (anterior intra-pelvic) with modified ilio-femoral along with 'anterior superior iliac spine' osteotomy. This combined approach provides wide exposure of pelvis to direct visualise the entire anterior column from sacroiliac joint to pubic symphysis, medial side of quadrilateral plate and entire iliac wing with minimal retraction of soft tissues required.

Methods: Data of patients treated from July 2014 to June 2018 for acetabulum fracture using CAP approach was retrieved from hospital record system. Inclusion criteria were - acetabulum fractures treated surgically using CAP approach. Exclusion criteria were - age less than 18 years, associated pelvis ring injury and incomplete peri-operative radiological record (pre-operative/post-operative antero-posterior, 45° obturator and 45° iliac oblique radiographs and pre-operative computed tomographic (CT) scans. 62 patients who met inclusion exclusion criteria were called in out-patient-department for final functional evaluation using Matta modified Merle d'aubigne score.

Results: Out of 62 patients 47 patients who turned up for final functional evaluation were included in study. 19 patients had excellent, 15 had good, 2 had fair and 11 had poor results. Age less than 40 years, anterior column fracture pattern, Pre-operative fracture displacement >20 mm, fracture comminution and post-operative fracture reduction within 3 mm were the predictors of the functional outcome. When analysed using logistic regression model, post-operative fracture reduction was found to be the only significant predictor of functional outcome.

Conclusion: CAP approach is useful anterior approach to acetabulum. Fracture reduction is the independent predictor of functional outcome. Comparison of this approach with other anterior approaches to acetabulum can be area of further research.
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http://dx.doi.org/10.1016/j.jcot.2020.10.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7656484PMC
October 2020

Reply By Authors.

J Urol 2021 01 10;205(1):84-85. Epub 2020 Nov 10.

Section of Urology, University of Manitoba, Winnipeg, Manitoba, Canada.

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http://dx.doi.org/10.1097/JU.0000000000001230.03DOI Listing
January 2021

Prognostic factors in patients with small renal masses: a comparison between <2 vs. 2.1-4 cm renal cell carcinomas.

Cancer Causes Control 2021 Feb 9;32(2):119-126. Epub 2020 Nov 9.

Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montreal Health Center, Montreal, Quebec, Canada.

Background: Few data factually support the prognostic distinction between renal cell carcinomas (RCC) < 2 vs. 2.1-4 cm, in terms of cancer-specific mortality (CSM). We investigated CSM rates over time in <2 vs. 2.1-4 cm RCC, according to patient and tumor characteristics.

Methods: Within the Surveillance, Epidemiology and End Results (SEER) database, we focused on patients with TNM RCC who underwent either radical or partial nephrectomy between 2000 and 2015. Temporal trends, Kaplan-Meier plots and multivariable Cox-regression analyses assessed CSM.

Results: Of 43,147 TNM patients, 12,238 (28.4%) harbored RCC < 2 cm and 30,909 (71.6%) 2.1-4 cm RCC. The distribution of histological subtypes according to 2 cm cut-off was as follows: a). clear-cell G1/G2: 64.5 vs. 61.8%; b). papillary G1/G2 15.9 vs. 11.1%; c). clear-cell G3/G4: 9.9 vs. 16.1%; d). papillary G3/G4 4.9 vs. 5.4%; and e). chromophobe 4.9 vs. 5.2%. Five-year CSM rates were invariably lower in RCC < 2 cm than in 2.1-4 cm, for all histological subtypes and grade groups (a-e), even after additional multivariable adjustment for age and residual tumor size differences. 5-year CSM rates improved in more contemporary years, in both tumor size groups (< 2 vs. 2.1-4 cm), but to a greater extent in 2.1-4 cm renal masses.

Conclusion: Our results validate the presence of prognostically more favorable CSM outcomes in RCC < 2 cm vs. 2.1-4 cm, across all histological subtypes and grades. Moreover, temporal improvements were also recorded in both <2 and 2.1-4 cm RCC groups, with more pronounced improvements in patients with 2.1-4 cm renal masses. However, prospective randomized trials are needed to further confirm our results.
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http://dx.doi.org/10.1007/s10552-020-01364-3DOI Listing
February 2021

Effect of COVID-19 on surgical management of open fractures and infection rates: A tertiary care experience in Indian set-up.

J Clin Orthop Trauma 2021 Jan 26;12(1):16-21. Epub 2020 Oct 26.

Department Of Orthopaedics, Government Medical College and Hospital, Chandigarh, India.

Background: Open fractures form one of the most common musculoskeletal injuries and are often complicated by infection. In this unprecedented situation, the additional infection rates, further add to the burden of the already compromised healthcare setup. The present study is done to see the effect of COVID-19 on management of open fractures.

Methods: A retrospective evaluation of patients with open fractures from March 25th 2020 to July 21st 2020 (group 1) and March 25th 2019 to July 21st 2019 (group 2) was performed. These patients were assessed for demographic details, diagnosis, type of surgery, delay from injury to admission, delay from admission to surgery, postoperative hospital stay, acute infection rates, readmission rates and associated injuries.

Results: A total of 52 patients with 59 open fractures in 2020 and 89 patients with 101 open fractures in 2019 met the inclusion criteria. The mean age was 34.76 years and 32.74 years in 2020 and 2019 respectively. Road side accidents were predominant in both the groups, comprising of 38 (73.07%) and 67 (75.28%) respectively(n.s.); adult patients were 42 (80.76%) and 79 (88.76%) respectively(n.s.); paediatric patients were 10 (19.23%) and 10 (11.23%) respectively(n.s.); tibia was the most common bone involved, comprising of 14 (23.72%) and 27 (26.73%) open fractures respectively(n.s.); external fixator was the most commonly used implant during COVID-19 time with 42 (71.18%) and 51 (50.49%) respectively(p = 0.005); the infection rate was 25.42% and 20.79% respectively(n.s.); the time for administration of first intravenous antibiotic dose was on 6.75 h and 4.04 h respectively(p < 0.0001); average time between the admission and surgical debridement was 24.04 h and 19.32 h respectively(n.s.); referral cases were 33 (63.46%) and 44 (49.43%) respectively(n.s.); re-admission rates were 7/52 (13.46%) and 10/89(11.23%) respectively(n.s.).

Conclusion: Despite the decrease in total trauma cases, a delay in presentation to the emergency room/administration of first dose of antibiotic and increase in temporary fixation in form of external fixator was observed. Further, an increase in infection rates, referral cases and readmission rates were observed, though not statistically significant.
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http://dx.doi.org/10.1016/j.jcot.2020.10.050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7587168PMC
January 2021

Small Renal Masses With Tumor Size 0 to 2 cm: A SEER-Based Study and Validation of NCCN Guidelines.

J Natl Compr Canc Netw 2020 10 1;18(10):1340-1347. Epub 2020 Oct 1.

1Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, Quebec, Canada.

Background: The NCCN Clinical Practice Guidelines in Oncology for Kidney Cancer recommend active surveillance as an option for initial management of T1a 0- to 2-cm renal lesions, in addition to partial nephrectomy, radical nephrectomy, and focal ablation. However, contemporary data regarding the distribution of patient and renal cell carcinoma characteristics within this special patient group are scarce.

Methods: Within the SEER database (2002-2016), 13,364 patients with T1aNanyMany 0- to 2-cm renal lesions treated with nephrectomy were identified. Data were tabulated according to histologic subtype, Fuhrman grade (FG1-2 vs FG3-4), age category, and sex. In addition, rates of synchronous metastases were quantified.

Results: Overall, clear-cell (69.3%), papillary (21.4%), chromophobe (6.9%), multilocular cystic (2.0%), sarcomatoid dedifferentiation (0.2%), and collecting-duct histologic subtypes (0.2%) were identified. Advanced age was associated with a lower rate of FG1-2 clear cell histologic subtype (70.8%-50.3%) but higher rates of FG1-2 papillary (11.1%-23.9%) and chromophobe histologic subtypes (6.2%-8.5%). Overall, 14.5% individuals harbored FG3-4 clear cell (9.8%) or FG3-4 papillary histologic subtypes (4.8%), and both were more prevalent in men. FG3-4 clear-cell and FG3-4 papillary histologic subtypes increased with age, more so in women than in men. The overall rate of synchronous metastases was 0.4% and ranged from 0 in the multilocular cystic subtype to 0.9% in the FG3-4 papillary histologic subtype, respectively, except for 13.8% in the sarcomatoid dedifferentiation histologic subtype.

Conclusions: Most T1a 0- to 2-cm renal cell carcinoma represents the low-grade clear-cell or low-grade papillary histologic subtype, with an FG3-4 minority. Even in patients with the FG3-4 histologic subtype, rates of synchronous metastases are virtually zero.
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http://dx.doi.org/10.6004/jnccn.2020.7577DOI Listing
October 2020

Expert and Crowdsourced Evaluation of Image Quality From a Novel Endoscopy Phone Light Adapter.

Urology 2020 Dec 2;146:54-58. Epub 2020 Oct 2.

Division of Urology, McMaster University, Hamilton, ON, Canada.

Objective: To evaluate the image quality of cystourethroscopy using a novel 3D printed phone light adapter with subject expert and crowdsourced evaluators.

Methods: A simple 3D printed light adaptor for a flexible cystoscopy was developed and made open source. Two videos were then recorded of a simulated cystourethroscopy, one using the novel adapter and the other using a traditional endoscopy light source. Expert evaluators (urology trainees and attendings) were then asked to evaluate the video quality using a double stimulus impairment scale. They were also asked to rate their level of confidence in using the novel adapter in clinical scenarios. Using Amazon's Mechanical Turk marketplace, 100 crowdsourced evaluators viewed the same videos and completed the same rating scale. The Mann-Whitney U test was then used to compare the expert and crowdsourced ratings.

Results: Expert and crowdsourced evaluators saw minimal degradation of video quality for the simulated urethroscopy (P= .66). However, while expert evaluators did identify degradation in the cystoscopy video, the crowdsourced evaluators did not (P = .012). 96% of the expert evaluators would either "often" or "always" use the novel adapter for difficult Foley placements and removal of ureteric stents.

Conclusion: The novel light adapter caused minimal degradation in image quality for urethroscopy as compared to a traditional endoscopy light source, with vast majority of raters believing it would be adequate to perform common bedside cystoscopy procedures.
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http://dx.doi.org/10.1016/j.urology.2020.09.034DOI Listing
December 2020

Prognostic impact of paraneoplastic syndromes on patients with non-metastatic renal cell carcinoma undergoing surgery: Results from Canadian Kidney Cancer information system.

Can Urol Assoc J 2020 Sep 28. Epub 2020 Sep 28.

Department of Surgery, University of Manitoba, Winnipeg, MN, Canada.

Introduction: The impact of paraneoplastic syndromes (PNS) on survival in patients with renal cell carcinoma (RCC) is uncertain. This study was conducted to analyze the association of PNS with recurrence and survival of patients with non-metastatic RCC undergoing nephrectomy.

Methods: The Canadian Kidney Cancer information system is a multi-institutional cohort of patients started in January 2011. Patients with nephrectomy for non-metastatic RCC were identified. PNS included anemia, polycythemia, hypercalcemia, and weight loss. Associations between PNS and recurrence or death were assessed using Kaplan-Meier curves and multivariable analysis.

Results: Of 4337 patients, 1314 (30.3%) had evidence of one or more PNS. Patients with PNS, were older, had higher comorbidity, and had more advanced clinical and pathological tumor characteristics as compared to patients without PNS (all p<0.05). Kaplan-Meier five-year estimated recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) were significantly worse in patients with PNS (63.7%, 84.3%, and 79.6%, respectively for patients with PNS vs. 73.9%, 90.8%, and 90.1%, respectively for patients without PNS, all p<0.005). On univariable analysis, presence of PNS increased risk of recurrence (hazard ratio [HR] 1.67, 95% confidence interval [CI] 1.48-1.90, p<0.0001) and cancer-related death (HR 1.85, 95% CI 1.34-2.54, p=0.0002). Adjusting for known prognostic factors, PNS was not associated with recurrence or survival.

Conclusions: In non-metastatic RCC patients undergoing surgery, presence of PNS is associated with older age, higher Charlson comorbidity index score, advanced tumor stage, and aggressive tumor histology. Following surgery, baseline PNS is not strongly independently associated with recurrence or death.
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http://dx.doi.org/10.5489/cuaj.6833DOI Listing
September 2020

Development, implementation, and evaluation of a competency-based didactic and simulation-focused boot camp for incoming urology residents: Report of the first three years.

Can Urol Assoc J 2020 Sep 28. Epub 2020 Sep 28.

Department of Surgery, Division of Urology, McMaster University, Hamilton, ON, Canada.

Introduction: The Royal College of Physicians and Surgeons of Canada's Competence by Design (CBD) initiative presents curricula challenges to ensure residents gain proficiency while progressing through training. To prepare first-year urology residents (R1s), we developed, implemented, and evaluated a didactic and simulation-focused boot camp to implement the CBD curriculum. We report our experiences and findings of the first three years.

Methods: Urology residents from two Canadian universities participated in the two-day boot camp at the beginning of residency. Eleven didactic and six simulation sessions allowed for instruction and deliberate practice with feedback. Pre-and post-course multiple-choice questionnaires (MCQs) and an objective structured clinical exam (OSCE) evaluated knowledge and skills uptake. For initial program evaluation, three R2s served as historical controls in year 1.

Results: Nineteen residents completed boot camp. The mean age was 26.4 (±2.8) and 13 were male. Participants markedly improved on the pre- and post-MCQs (year 1: 62% and 91%; year 2: 55% and 89%; year 3: 58% and 86%, respectively). Participants scored marginally higher than the controls on four of the six OSCE stations. OSCE scores remained >88% over the three cohorts. All participants reported higher confidence levels post-boot camp and felt it was excellent preparation for residency.

Conclusions: During its first three years, our urology boot camp has demonstrated high feasibility and utility. Knowledge and technical skills uptake were established via MCQ and OSCE results, with participants' scores near or above those of R2 controls. This boot camp will remain in our CBD curriculum and can provide a framework for other urology residency programs.
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http://dx.doi.org/10.5489/cuaj.6679DOI Listing
September 2020

Prevalence of concomitant knee injuries associated with anterior cruciate ligament tear in kabaddi and football players.

J Clin Orthop Trauma 2020 Oct 6;11(Suppl 5):S784-S788. Epub 2020 Jun 6.

Department of Orthopaedics, Government Medical College Hospital, Chandigarh, India.

Background: There is little literature available about the type of sports and concomitant knee injury.

The Purpose Of The Study: To help in better prediction of concomitant knee injuries in football and kabaddi players.

Material Method: Five hundred and seventeen male athletes [Football (n = 226) and Kabaddi players (n = 291)] aged between 16 and 35 years were enrolled in the study. These were categorized into five groups depending upon the time interval between injury and surgery (0-3 months, 3-6 months, 6-9 months, 9-12 months, 12-18 months and 18-24 months). Meniscal and chondral damage present at the time of ACL reconstruction was documented.

Results: The overall incidence of meniscal tear was more in kabaddi players (220/291) as compared to football players (144/226; p = 0.003). The incidence of both menisci tear was more in kabaddi as compared to football (p = 0.02). Incidence of lateral meniscus tear (147/291) in kabaddi was more as compared to football (84/226; p = 0.002). The incidence of condylar damage was comparable in both groups. Medial femoral condyle was more commonly injured in both the sports irrespective of time frame.

Conclusion: The chances of meniscus injuries were more in kabaddi players compared to football players in ACL deficient knee. The time interval between injury and surgery had a direct correlation with meniscus and chondral injuries.

Level Of Evidence: Level III, retrospective study.
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http://dx.doi.org/10.1016/j.jcot.2020.05.037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7503079PMC
October 2020

Real-world management of advanced prostate cancer: A description of management practices of community-based physicians and prostate cancer specialists.

Can Urol Assoc J 2021 Feb;15(2):E90-E96

Centre hospitalier de l'Université de Montréal, Montreal, QC, Canada.

Introduction: The Canadian Genitourinary Research Consortium (GURC) conducted a consensus development conference leading to 31 recommendations. Using the GURC consensus development questionnaire, we conducted a survey to measure the corresponding community-based practices on the management of metastatic castration-sensitive prostate cancer (mCSPC), metastatic castration-resistant prostate cancer (mCRPC) and non-metastatic castration-resistant prostate cancer (nmCRPC).

Methods: An 87-item online questionnaire was sent to 600 community urologists and oncologists involved in the treatment of prostate cancer.

Results: Seventy-two community physicians responded to the survey. Of note, 50% community physicians indicated they would treat nmCRPC with agents approved for this indication if advanced imaging showed metastases. Radiation to the prostate for low-volume mCSPC was identified as a treatment practice by 27% of community physicians, and 35% indicated docetaxel as the next line of treatment after use of apalutamide. Use of genetic testing was reported in 36% of community physicians for newly diagnosed metastatic prostate cancer.

Conclusions: There are several areas of community-based management of advanced prostate cancer that could represent potential areas for education, practice tools, and future research.
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http://dx.doi.org/10.5489/cuaj.6779DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864716PMC
February 2021

No Difference in Outcome of Anterior Cruciate Ligament Reconstruction with "Bone-patellar Tendon-bone versus Semitendinosus-gracilis Graft with Preserved Insertion": A Randomized Clinical Trial.

Indian J Orthop 2020 Sep 28;54(5):665-671. Epub 2020 Apr 28.

Department of Orthopaedics, Government Medical College Hospital, Chandigarh, India.

Background: The type of graft for anterior cruciate ligament (ACL) reconstruction is still a topic of debate and there is still no clear consensus on the ideal graft for ACL reconstruction.

Purpose: This study was conducted to compare the outcome of ACL reconstruction surgery between hamstring tendon graft and bone-patellar tendon-bone (BPTB) graft.

Materials And Methods: One hundred and sixty professional athletes were enrolled in the study. They were divided into two groups by computerized randomization. In Group I, ACL reconstruction was done using BPTB graft, and in Group II, ACL reconstruction was done using semitendinosus gracilis graft with preserved tibial insertion (STGPI). Postoperatively, patients were assessed for knee stability, Lysholm score, and WOMAC score.

Results: Mean KT-1000 side-to-side difference at 1 year was 2.31 ± 1.68 mm in BPTB cohort and 2.52 ± 1.6 mm in STGPI cohort ( = 0.4); and at 2 years, it was 1.98 ± 1.62 mm in BPTB cohort and 2.23 ± 1.6 mm in STGPI cohort ( = 0.4). Mean Lysholm score at 2 years was 96.1 ± 5.81 in STGPI cohort and 97.3 ± 4.62 in BPTB cohort ( = 0.15). Mean WOMAC score at 2 years was 3.3 ± 2.76 in STGPI cohort and 2.84 ± 2.21 in BPTB cohort ( = 0.25). Graft rupture rate was 3.75%; 3 patients in each group had graft rupture. Kneeling pain was present in 15% (12/80) of patients with BPTB graft whereas none of the patients in STGPI cohort had kneeling pain.

Conclusion: There was no difference between two grafts in term of knee stability, visual analog scale score and functional outcome. However, hamstring tendon graft is associated with less donor site morbidity.
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http://dx.doi.org/10.1007/s43465-020-00073-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7429638PMC
September 2020

Images - Rare diagnosis of high-grade, undifferentiated pelvic sarcoma for urinary dysfunction in a young man.

Can Urol Assoc J 2020 Aug 7. Epub 2020 Aug 7.

McMaster Institute of Urology, Hamilton, ON, Canada.

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http://dx.doi.org/10.5489/cuaj.6703DOI Listing
August 2020

Contemporary Cytoreductive Nephrectomy Provides Survival Benefit in Clear-cell Metastatic Renal Cell Carcinoma.

Clin Genitourin Cancer 2020 Dec 20;18(6):e730-e738. Epub 2020 May 20.

Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, QC, Canada; Division of Urology, University of Montreal Hospital Center (CHUM), Montreal, QC, Canada.

Introduction: A recent randomized trial questioned the role of cytoreductive nephrectomy in clear-cell metastatic renal cell carcinoma (ccmRCC). We reassessed the effect of cytoreductive nephrectomy on survival in a contemporary population-based ccmRCC cohort.

Patients And Methods: Within the Surveillance, Epidemiology, and End Results database (2010-2015), we focused on patients with ccmRCC. The primary endpoint consisted of overall mortality. Univariable and multivariable Cox regression models were applied in the overall cohort and in patients who underwent targeted therapy. Sensitivity analyses included 1:1 propensity score matching, 3- and 6-month landmark analyses, incremental survival benefit analyses, and metastases number and location-based stratifications.

Results: Of 4062 patients with ccmRCC, 2241 (55.1%) received targeted therapy; cytoreductive nephrectomy was performed in 2226 (54.8%) patients and 1168 (52.1%) patients in the overall and targeted therapy cohorts, respectively. Cytoreductive nephrectomy was associated with lower overall mortality in the overall cohort (median survival, 30 vs. 9 months; hazard ratio [HR], 0.43; P < .001), as well as in the targeted therapy cohort (median survival, 28 vs. 12 months; HR, 0.49; P < .001). In sensitivity analyses, cytoreductive nephrectomy was associated with lower overall mortality after 1:1 propensity score-matching (HR, 0.49; P < .001), in 3- and 6-month landmark analyses (HR, 0.49; P < .001 and HR, 0.51; P < .001, respectively), in metastases number and location-based stratifications, except for exclusive liver metastases, as well as in all incremental benefit analyses.

Conclusion: Cytoreductive nephrectomy is associated with better survival in patients with ccmRCC, including those exposed to targeted therapy, after adjustment for multiple potential confounders.
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http://dx.doi.org/10.1016/j.clgc.2020.05.009DOI Listing
December 2020

Outcomes of complete metastasectomy in metastatic renal cell carcinoma patients: The Canadian Kidney Cancer information system experience.

Urol Oncol 2020 Oct 7;38(10):799.e1-799.e10. Epub 2020 Aug 7.

Faculty of Medicine, McGill University, Montreal, QC, Canada.

Background: Surgical resection of metastasis can be integrated in the management of metastatic renal cell carcinoma (mRCC) as it can contribute to delay disease progression and improve survival.

Objective: This study assessed the impact of complete metastasectomy in mRCC patients using real-world pan-Canadian data.

Design, Setting And Participants: The Canadian Kidney Cancer information system (CKCis) database was used to select patients who were diagnosed with mRCC between January 2011 and April 2019. To minimize selection bias, each patient having received a complete metastasectomy was matched with up to 4 patients not treated with metastasectomy.

Outcome Measurements And Statistical Analysis: Overall survival (OS) was calculated from the date of metastasectomy or selection, to death from any cause. A Cox proportional hazards model was used to assess the impact of the metastasectomy while adjusting for potential confounding variables.

Results: A total of 229 patients undergoing complete metastasectomy were matched with 803 patients not treated with metastasectomy. After matching, baseline characteristics were well balanced between groups. After 12 months, the proportion of patients that were still alive was 96.0% and 89.8% in the complete metastasectomy and its matched group, respectively; the 5-year OS were 63.2% and 51.4%, respectively. Multivariate analysis performed in the matched cohort revealed that patients who underwent complete metastasectomy had a lower risk of mortality compared to patients who did not undergo metastasectomy (hazard ratio: 0.41, 95% confidence interval:0.27-0.63).

Conclusion: Our study found that patients who underwent complete metastasectomy have a longer overall survival and a longer time to initiation of targeted therapy compared to patients not receiving metastasectomy. These findings should support aggressive resection of metastasis in selected patients.
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http://dx.doi.org/10.1016/j.urolonc.2020.07.021DOI Listing
October 2020

Contactin 1: An Important and Emerging Oncogenic Protein Promoting Cancer Progression and Metastasis.

Genes (Basel) 2020 07 31;11(8). Epub 2020 Jul 31.

Department of Medicine, McMaster University, Hamilton, ON L8S 4K1, Canada.

Even with recent progress, cancer remains the second leading cause of death, outlining a need to widen the current understanding on oncogenic factors. Accumulating evidence from recent years suggest Contactin 1 (CNTN1)'s possession of multiple oncogenic activities in a variety of cancer types. CNTN1 is a cell adhesion molecule that is dysregulated in many human carcinomas and plays important roles in cancer progression and metastases. Abnormalities in CNTN1 expression associate with cancer progression and poor prognosis. Mechanistically, CNTN1 functions in various signaling pathways frequently altered in cancer, such as the vascular endothelial growth factor C (VEGFC)-VEGF receptor 3 (VEFGR3)/fms-related tyrosine kinase 4 (Flt4) axis, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT), Notch signaling pathway and epithelial-mesenchymal transition (EMT) process. These oncogenic events are resulted via interactions between tumor and stroma, which can be contributed by CNTN1, an adhesion protein. CNTN1 expression in breast cancer correlates with the expression of genes functioning in cancer-stroma interactions and skeletal system development. Evidence supports that CNTN1 promotes cancer-stromal interaction, resulting in activation of a complex network required for cancer progression and metastasis (bone metastasis for breast cancer). CNTN1 inhibitions has been proven to be effective in experimental models to reduce oncogenesis. In this paper, we will review CNTN1's alterations in cancer, its main biochemical mechanisms and interactions with its relevant cancer pathways.
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http://dx.doi.org/10.3390/genes11080874DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465769PMC
July 2020

Comparison of a magnetic retrieval device vs. flexible cystoscopy for removal of ureteral stents in renal transplant patients: A randomized controlled trial.

Can Urol Assoc J 2021 Feb;15(2):E97-E102

Department of Surgery, Division of Urology, McMaster University, Hamilton, ON, Canada.

Introduction: Placement of a ureteral stent at the time of renal transplantation can reduce complications when compared to non-stented anastomoses. Removal by flexible cystoscopy can be associated with discomfort, risk for infection, and high costs. New magnetic stents offer a means of bypassing cystoscopy by use of a magnetic retrieval device. Our objective was to compare clinical and cost-related outcomes of conventional and magnetic stents in patients undergoing deceased donor renal transplantation.

Methods: Patients were randomized to receive either a conventional or a Black-Star magnetic stent. Clinical, procedural, and cost outcomes were assessed, and the Ureteral Stent Symptom Questionnaire (USSQ) was administered with the stent in situ and after stent removal. All variables were compared between groups.

Results: Forty-one patients were randomized to conventional (n=19) or Black-Star (n=22) stent. The total time for stent removal under cystoscopy was significantly longer compared to Black-Star removal (6.67±2.47 and 4.80±2.21 minutes, respectively, p=0.019). No differences were found in the USSQ domains between groups. Rates of urinary tract infections and surgical complications between groups were similar. Stent removal was well-tolerated in both groups. Black-Star stent use resulted in a cost savings of $304.02 Canadian dollars (CAD) per case.

Conclusions: USSQ scores suggest that stent removal with the Black-Star magnetic stent is as equally well-tolerated as flexible cystoscopy by renal transplant patients. Black-Star stent removal was significantly faster than conventional stents. No differences in discomfort, infection rate, or complication rate were found. Use of the Black-Star stent resulted in an estimated annual savings of $27 360 CAD at our centre.
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http://dx.doi.org/10.5489/cuaj.6684DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864704PMC
February 2021