Modern Management of Localized Renal Cell Carcinoma— Is Ablation Part of the Equation?

While the gold-standard for management of localized renal cell carcinoma (RCC) is partial nephrectomy, recent ablative strategies are emerging as alternatives with comparable rates of complications and oncologic outcomes. Thermal ablation, in the form of radiofrequency ablation and cryoablation, is being increasingly accepted by professional societies, and is particularly recommended in patients with a significant comorbidity burden, renal impairment, old age, or in those unwilling to undergo surgery. Maturation of long-term oncologic outcomes has further allowed increased confidence in these management strategies. New and exciting ablation technologies such as microwave ablation, stereotactic body radiotherapy, and irreversible electroporation are emerging. In this article, we review the existing management options for localized RCC, with specific focus on the oncologic outcomes associated with the various ablation modalities

The Impact of COVID-19 on Surgical Training and Education

The COVID-19 pandemic disrupted conventional medical education for surgical trainees with respect to clinical training, didactics, and research. While the effects of the COVID-19 pandemic on surgical trainees were variable, some common themes are identifiable. As hordes of COVID-19 patients entered hospitals, many surgical trainees stepped away from their curricula and were redeployed to other hospital units to care for COVID-19 patients. Moreover, the need for social distancing limited traditional educational activities. Regarding clinical training, some trainees demonstrated reduced case logs and decreased surgical confidence. For residents, fellows, and medical students alike, most didactic education transitioned to virtual platforms, leading to an increase in remote educational resources and an increased emphasis on surgical simulation. Resident research productivity initially declined, although the onset of virtual conferences provided new opportunities for trainees to present their work. Finally, the pandemic was associated with increased anxiety, depression, and substance use for some trainees. Ultimately, we are still growing our understanding of how the COVID-19 pandemic has redefined surgical training and how to best implement the lessons we have learned

Renal Cell Carcinoma with Cardiac Metastases: A Case Report and Review of the Literature

Cardiac metastases from renal cell carcinoma (RCC) are very rare. We describe the case of a woman with RCC with cardiac metastases involving the entire right atrium, penetrating through the myocardium, with extension into the tricuspid valve and right ventricle. This report highlights the unique challenge of the diagnosis and treatment of cardiac metastases in RCC

Massive Malignant Epithelioid Angiomyolipoma of the Kidney

Renal angiomyolipomas (AMLs) are a subset of perivascular epithelioid cell neoplasms (PEComas) that are associated with tuberous sclerosis complex (TSC). Epithelioid angiomyolipomas (EAMLs) are a rare variant of AML with more aggressive propensities. EAMLs with malignant potential can be difficult to distinguish from relatively benign AMLs and other renal tumors. Although there are no established criteria for predicting EAML malignancy, there are proposed histologic parameters that are associated with higher tumor risk. EAML can be treated with surgical resection as well as mTOR inhibitors. Here, we present a unique case of a patient with a 36-cm renal EAML metastatic to the lungs that was treated with complete surgical resection of the primary lesion and mTOR inhibition

Open versus robotic cystectomy: Comparison of outcomes

Open radical cystectomy (ORC) is the current gold standard treatment for muscle invasive bladder cancer. As surgeons become more proficient in minimally invasive and robotic surgical techniques, the number of patients undergoing robotic-assisted radical cystectomy (RARC) is increasing. Although minimally invasive methods are on the rise, research that critically compares open surgery with robotic methods is limited. In this review, we surveyed and appraised the current literature comparing ORC and RARC with regards to perioperative, functional, and oncologic outcomes in order to distinguish the benefits and disadvantages of each method. Here we report that RARC is associated with several perioperative advantages over ORC such as lower estimated blood loss and transfusion rate, and possibly faster gastrointestinal recovery, lower narcotic requirement, and shorter length of stay. ORC is less costly and permits less time in the operating room. Recent data suggests that there is no difference between ORC and RARC when comparing urinary continence and postoperative quality of life. Moreover, ORC and RARC are both associated with similar rates of obtaining positive surgical margins, lymph node yield, and recurrence. However, RARC patients had an increased likelihood of having distant metastases to extrapelvic lymph nodes and the peritoneum. At this point, it is unclear if ORC or RARC has superior patient outcomes, and more research is needed to ascertain management-altering conclusions

Anoxia-Reoxygenation Regulates Mitochondrial Dynamics through the Hypoxia Response Pathway, SKN-1/Nrf, and Stomatin-Like Protein STL-1/SLP-2

<div><p>Many aerobic organisms encounter oxygen-deprived environments and thus must have adaptive mechanisms to survive such stress. It is important to understand how mitochondria respond to oxygen deprivation given the critical role they play in using oxygen to generate cellular energy. Here we examine mitochondrial stress response in <i>C. elegans</i>, which adapt to extreme oxygen deprivation (anoxia, less than 0.1% oxygen) by entering into a reversible suspended animation state of locomotory arrest. We show that neuronal mitochondria undergo DRP-1-dependent fission in response to anoxia and undergo refusion upon reoxygenation. The hypoxia response pathway, including EGL-9 and HIF-1, is not required for anoxia-induced fission, but does regulate mitochondrial reconstitution during reoxygenation. Mutants for <i>egl-9</i> exhibit a rapid refusion of mitochondria and a rapid behavioral recovery from suspended animation during reoxygenation; both phenotypes require HIF-1. Mitochondria are significantly larger in <i>egl-9</i> mutants after reoxygenation, a phenotype similar to stress-induced mitochondria hyperfusion (SIMH). Anoxia results in mitochondrial oxidative stress, and the oxidative response factor SKN-1/Nrf is required for both rapid mitochondrial refusion and rapid behavioral recovery during reoxygenation. In response to anoxia, SKN-1 promotes the expression of the mitochondrial resident protein Stomatin-like 1 (STL-1), which helps facilitate mitochondrial dynamics following anoxia. Our results suggest the existence of a conserved anoxic stress response involving changes in mitochondrial fission and fusion.</p></div

SKN-1 is required for anoxia-induced mitochondrial hyperfusion.

<p>The fluorescence of MitoGFP was observed along ventral cord neurites of (A,B,C) wild-type animals, (D,E,F) <i>skn-1(tm3411)</i> mutants, and (G,H,I) <i>egl-9(sa307) skn-1(tm3411)</i> double mutants under conditions of (A,D,G) normoxia, (B,E,H) following 24 hours of anoxia, or (C,F,I) following 3 hours of reoxygenation post-anoxia. (J,K) Quantification of the mean (J) length and (K) number of mitochondria along the ventral cord for the indicated genotypes and conditions. (L) Quantification of behavioral recovery (number of animals moving after 10 minutes of reoxygenation) of animals following 24 hours anoxia. Red bars indicate normoxia, blue bars indicate anoxia, and purple stippled bars indicate reoxygenation. ANOVA followed by Dunnett's multiple comparison to wild type, normoxia (***p<0.001, **p<0.01, *p<0.05). N = 15–35 animals per condition and/or genotype. Error bars indicate SEM. Bar, 5 µm.</p

Anoxia promotes suspended animation and eventually death in <i>C. elegans</i>.

<p>(A) Protocol for <i>C. elegans</i> anoxia treatment. The x-axis indicates time (in days since fertilization) and developmental stage (“EM” for embryo, “L2” and “L4” for respective larval stages, and “A1–A6” for the indicated day of mature adulthood). Boxes indicate the treatment during that particular period, with red indicating exposure to a normoxic environment (or the 1-day reoxygenation, labeled as “Re”) and blue indicating exposure to an anoxic environment. (B) Mean percentage of animals surviving after the given exposure time to anoxia. Error bars indicate SEM. (C) Mean percentage of animals moving (i.e., recovered from suspended animation) at the given time point following reoxygenation (post-anoxia). Individually plotted lines represent recovery following 12 (filled squares), 24 (filled triangles), 36 (empty triangles), and 48 (empty circles) hours of anoxia exposure. N = 15–35 animals per condition and/or genotype.</p

Model for anoxia-induced mitochondrial hyperfusion.

<p>Under conditions of normoxia in wild-type neurons, mitochondria undergo a balance of fission and fusion. Exposure to anoxia shifts the balance towards smaller and fewer mitochondria by promoting the canonical fission process. Reoxygenation shifts the balance back towards elongated mitochondria by promoting the canonical fusion process. Depending on the dual activities of the hypoxia response pathway (EGL-9 and HIF-1) and the oxidative stress pathway (SKN-1 and STL-1), reoxygenation can trigger hyperfusion, rapidly resulting in enlarged mitochondria. Mitochondrial dynamics in turn affect the suspended animation behavior of the animal. Hyperfused mitochondria, perhaps through a more efficient generation of ATP, allow neurons to rapidly resume function and rapidly re-emerge from suspended animation. Green ellipses indicate mitochondria distributed along neurites. Arrows indicate stimulatory interactions, whereas T-bars indicate inhibitory interactions.</p