Perioperative systemic treatments in renal cell carcinoma

In this review, we aim to provide a comprehensive assessment of the evolving landscape of the perioperative management in renal cell carcinoma (RCC), emphasizing its dynamic and intricate nature. We explore academic and clinical insights into the perioperative treatment paradigm of RCC. Up-to-date treatment options are discussed and the evolving role of neoadjuvant and adjuvant therapy in RCC is highlighted

Predictive Nomogram for Recurrence following Surgery for Nonmetastatic Renal Cell Cancer with Tumor Thrombus

Purpose Following surgery for nonmetastatic renal cell carcinoma with tumor thrombus the risk of recurrence is significant but variable among patients. The purpose of this study was to develop and validate a predictive nomogram for individual estimation of recurrence risk following surgery for renal cell carcinoma with venous tumor thrombus. Materials and Methods Comprehensive data were collected on patients with nonmetastatic renal cell carcinoma and thrombus treated at a total of 5 institutions from 2000 to 2013. Independent predictors of recurrent renal cell carcinoma from a competing risks analysis were developed into a nomogram. Predictive accuracy was compared between the development and validation cohorts, and between the nomogram and the UISS (UCLA Integrated Staging System, SSIGN (Stage, Size, Grade and Necrosis) and Sorbellini models. Results A total of 636 patients were analyzed, including the development cohort of 465 and the validation cohort of 171. Independent predictors, including tumor diameter, body mass index, preoperative hemoglobin less than the lower limit of normal, thrombus level, perinephric fat invasion and nonclear cell histology, were developed into a nomogram. Estimated 5-year recurrence-free survival was 49% overall. Five-year recurrence-free survival in patients with 0, 1, 2 and more than 2 risk factors was 77%, 53%, 47% and 20%, respectively. Predictive accuracy was similar in the development and validation cohorts (AUC 0.726 and 0.724, respectively). Predictive accuracy of the thrombus nomogram was higher than that of the UISS (AUC 0.726 vs 0.595, p = 0.001), SSIGN (AUC 0.713 vs 0.612, p = 0.04) and Sorbellini models (AUC 0.709 vs 0.638, p = 0.02). Conclusions We present a predictive nomogram for postoperative recurrence in patients with nonmetastatic renal cell carcinoma with venous thrombus. Improving individual postoperative risk assessment may allow for better design and analysis of future adjuvant clinical trials

Impact of Nanopore Flow Cell Types on DNA Methylation Detection

Third-generation sequencing technologies have revolutionized the study of epigenetic characteristics in human diseases, with Oxford Nanopore Technologies (ONT) at the forefront of long-read sequencing. ONT has made rapid improvements in flow cell designs, which greatly increased its sequencing accuracy but, at the same time, led to some projects utilizing different flow cell types, mainly R9 vs. R10, across samples. Whether and how the flow cell types affect genome-wide DNA methylation detection remains incompletely understood. Here, we used both flow cell types to analyze 6 human renal cell carcinoma (RCC) samples and compared the results. While there was a highly significant correlation between 5-methylcytosine (5mC) detected by R9 and R10 flow cells, we also observed substantial differences. R9 flow cells over-estimated 5mC levels at hypomethylated chromatin regions, mostly at promoters, while under-estimated 5mC at hypermethylated chromatin regions, enriched at intronic and intergenic regions. Such deviations in detection were likely caused by substantially lower sequencing accuracy of R9 flow cells, due to its mechanics, especially having problems sequencing homopolymeric DNA elements, such as CpG islands, leading to both higher false-positive and false-negative detections. Interestingly, such systematic errors were largely mitigated by batch-correction software, improving data comparability. In summary, our study reports superior performance of R10 flow cells, leading to much higher accuracy in base sequencing and DNA methylation detection

Mayo Adhesive Probability Score Does Not Have Prognostic Ability in Locally Advanced Renal Cell Carcinoma

Nephrectomy remains standard treatment for renal cell carcinoma (RCC). The Mayo Adhesive Probability (MAP) score is predictive of adherent perinephric fat and associated surgical complexity, and is determined by assessing perinephric fat and stranding. MAP has additionally predicted progression-free survival (PFS), though primarily reported in stage T1-T2 RCC. Here, we examine MAP’s ability to predict overall survival (OS) and PFS in T3-T4 RCC. From our prospectively maintained RCC database, patients that underwent radical nephrectomy (2009-2016) with available abdominal imaging (<90 days preop) and T3/T4 RCC underwent MAP scoring. Survival analyses were conducted with MAP scores as individual (0-5) and dichotomized (0-3 vs 4-5) using Kaplan-Meier method. Multivariable Cox proportional hazard regression models for PFS and OS were built with backward elimination. 141 patients were included. 134 (95%) and 7 (5%) had pT3 and pT4 disease, respectively. 46.1% of patients had an inferior vena cava thrombus. Mean MAP score was 3.22±1.52, with 75 (53%) patients having a score between 0-3 and 66 (47%) having a score of 4-5. Both male gender (p=0.006) and clear cell histology (p=0.012) were associated with increased MAP scores. On Kaplan-Meier and multivariable analysis, no significant associations were identified between MAP and PFS (HR=1.01, 95% CI 0.85-1.20, p=0.93) or OS (HR=1.01, 95% CI 0.84-1.21, p=0.917). In this cohort of patients with locally advanced RCC, high MAP scores were not predictive of worse PFS or OS

Surgical Education International surgical clerkship rotation: perceptions and academic performance

Abstract BACKGROUND: Concerns about international training experiences in medical school curricula include the effect on student learning. We studied the educational effect of an international elective integrated into a traditional third-year (M3) surgical clerkship. METHODS: A 1-week surgical elective in Haiti was available to M3 students during the conventional 8-week surgical clerkship each year for the 4 academic years 2008 to 2011. The authors collected student and surgeon perceptions of the elective using a mixed-methods web-based survey. Statistical analysis compared the academic performance of participating M3s relative to nonparticipating peers. RESULTS: Twenty-eight (100%) students (41 trip weeks) and 3 (75%) surgeons responded. Twentyfive (89%) students believed the elective provided appropriate clinical training. Surgeon responses were consistent with students' reported perceptions. Strengths included unique clinical experiences and close interactions with faculty. Criticisms included recurring overwhelming clinical responsibilities and lack of local provider involvement. Academic performance of participants versus nonparticipants in the same clerkship term were statistically insignificant. CONCLUSIONS: This study demonstrates the feasibility of integrating global health experiences into traditional medical student clinical curricula. The effects on less tangible attributes such as leadership skills, fostering teamwork, and cultural competency require future investigation

Neoadjuvant and Adjuvant Therapy for Renal Cell Carcinoma

Patients undergoing definitive surgery or ablative techniques for nonmetastatic kidney cancer have varying degrees of risk of recurrent disease post procedure. The ultimate goal of “adjuvant therapy” is to reduce the incidence of recurrent disease, and to cure more patients. We summarize the current state of perioperative therapy for kidney cancer and explore future directions to develop optimal adjuvant strategies. We define risk and risk of recurrence post-definitive therapy, describe the controversies surrounding the trial landscape of adjuvant vascular endothelial growth factor receptor tyrosine kinase inhibitors and immune checkpoint inhibitors. We review data on neoadjuvant therapy before advanced kidney cancer resection. Radiologic, ethnic, economic, and geographic considerations with respect to adjuvant therapy are highlighted, as well as adjuvant therapy issues especially pertinent to patients, future directions in adjuvant trial design specifically targeted to biomarkers and patient selection, and sequencing of treatment after adjuvant therapy in those patients with recurrence

Intensive medical student involvement in short-term surgical trips provides safe and effective patient care: a case review

<p>Abstract</p> <p>Background</p> <p>The hierarchical nature of medical education has been thought necessary for the safe care of patients. In this setting, medical students in particular have limited opportunities for experiential learning. We report on a student-faculty collaboration that has successfully operated an annual, short-term surgical intervention in Haiti for the last three years. Medical students were responsible for logistics and were overseen by faculty members for patient care. Substantial planning with local partners ensured that trip activities supplemented existing surgical services. A case review was performed hypothesizing that such trips could provide effective surgical care while also providing a suitable educational experience.</p> <p>Findings</p> <p>Over three week-long trips, 64 cases were performed without any reported complications, and no immediate perioperative morbidity or mortality. A plurality of cases were complex urological procedures that required surgical skills that were locally unavailable (43%). Surgical productivity was twice that of comparable peer institutions in the region. Student roles in patient care were greatly expanded in comparison to those at U.S. academic medical centers and appropriate supervision was maintained.</p> <p>Discussion</p> <p>This demonstration project suggests that a properly designed surgical trip model can effectively balance the surgical needs of the community with an opportunity to expose young trainees to a clinical and cross-cultural experience rarely provided at this early stage of medical education. Few formalized programs currently exist although the experience above suggests the rewarding potential for broad-based adoption.</p

Phase 2 Study of the Efficacy and Safety of Erdafitinib in Patients With Bacillus Calmette-Guérin (BCG)-Unresponsive, High-Risk Non–Muscle-Invasive Bladder Cancer (HR-NMIBC) With FGFR3/2 Alterations (alt) in THOR-2: Cohort 2 Interim Analysis Results

Patients presenting with NMIBC carcinoma in situ (CIS) have a high risk of progression1,2FGFR inhibition may benefit patients with CIS with FGFRalt who are unresponsive to fi rst-line BCG, for whom treatment options, other than radical cystectomy, are limited3-5– Data are limited in patients with CIS only, but in the broader NMIBC population the prevalence of FGFR3alt is up to 80%6Erdafi tinib, an oral selective pan-FGFR tyrosine kinase inhibitor, is approved for locally advanced or metastatic urothelial cancer in adults with susceptible FGFR3/2alt who have progressed during or after ≥1 line of platinum-containing chemotherapy7-9 THOR-2 (NCT04172675) is a multicohort phase 2 study of erdafi tinib in patients with HR-NMIBC

Differences in failure-free survival after salvage radiotherapy guided by conventional imaging versus 18F-fluciclovine PET/CT in postprostatectomy patients : a post hoc substratification analysis of the EMPIRE-1 trial

Please read abstract in the article.The National Institutes of Health and Blue Earth Diagnostics.http://jnm.snmjournals.orghj2023Nuclear Medicin

Renal cell carcinoma with inferior vena cava involvement: Prognostic effect of tumor thrombus consistency on cancer specific survival: Tumor Thrombus Consistency and Survival

Renal cell carcinoma forming a venous tumor thrombus (VTT) in the inferior vena cava (IVC) has a poor prognosis. Recent investigations have been focused on prognostic markers of survival. Thrombus consistency (TC) has been proposed to be of significant value but yet there are conflicting data. The aim of this study is to test the effect of IVC VTT consistency on cancer specific survival (CSS) in a multi-institutional cohort