Maroun, Justin W.

Importance: Lung cancer and pulmonary metastases remain the leading cause of cancer-related mortality. While surgery is the gold standard, local tissue-ablative therapies are increasingly used in unresectable disease or inoperable patients. Minimally invasive local control presents a safe, repeatable approach to slow disease progression and prolong survival. Observations: Ablative techniques (radiofrequency, microwave, cryoablation, pulsed electric field) utilize extreme heat, cold, or energy to induce cancer cell death. Traditionally, ablation occurred percutaneously with image guidance, but transbronchial approaches are gaining popularity due to a potentially improved complication profile with reduced tumoral seeding. Stereotactic body radiotherapy utilizes non-invasive, precise radiation with a steep dose fall-off to protect peritumoral tissue. Transarterial infusions via transarterial chemoembolization and intraarterial chemoperfusion are emerging approaches that exploit tumor vasculature to provide focal cytotoxicity and ischemia. Intratumoral injectables (chemotherapy, immunotherapy, radiosensitization, oncolytic viruses, adoptive cell therapy, and chimeric antigen receptor T-cell therapy) directly target the tumor microenvironment, potentially increasing efficacy whilst minimizing systemic adverse effects. Conclusions and relevance: In the age of individualized cancer therapy, a multidisciplinary approach with concurrent modalities can achieve local control. This review provides a comprehensive discussion regarding the role and types of local control, safety, efficacy, and survival outcomes in assessing percutaneous, transbronchial, intraarterial, and intratumoral approaches in nonsurgical patients.

Abstract Disclosure: B. Bahrani Fard: None. N. Nikravangolsefid: None. J. Maroun: None. A. Cross: None. T. Foster: None. T. McKenzie: None. W. Young Jr: None. B.M. Dy: None. M. Lyden: None. I. Bancos: None. Background: Giant pheochromocytomas (PHEO), defined based on size > 10 cm, are rare. Data on clinical presentation, management, and prognosis of giant PHEOs are scarce. Objectives: to determine prevalence of giant PHEO and compare presentation, management, and outcomes of patients with giant vs non-giant PHEOs. Methods: We conducted a single-center retrospective cohort study of consecutive patients with giant PHEO and randomly chosen patients with non-giant PHEO (referents) at 6:1 ratio, evaluated between 2000-2023. All variables were extracted from the electronic medical record. Results: Of 828 patients with PHEO evaluated between 2000 and 2023, 31 (3.7%) had giant PHEO (median size 12 cm, IQR 10.0-13.5). In comparison to referents (n=186, median size 4 cm, IQR, 2.9-5.0), patients with giant PHEO were similar in age (median age 53 vs 55 years, P=.55), more frequently discovered based on symptoms (52% vs 32%, P=.04), and less likely to be bilateral (3% vs 12%, P=.31). Genetic testing was performed in 103 (48%) of patients, without group differences, however, patients with giant PHEO were less likely to have an associated germline mutation detected (7% vs 47%, P=.004). Patients with giant PHEO had more symptoms of catecholamine excess (median of 2 vs 1, P=.04) and presented with a higher prevalence of severe metanephrine excess >10 times above upper normal range (76% vs 30%, P<.0001). Adrenalectomy was performed in 94% of patients with giant PHEOs and in 100% referents, with higher rates of open adrenalectomy in giant PHEO (86% vs 14%, P<.0001). In addition to preoperative alpha-adrenergic blockade (89%), metyrosine was used in 14 (7%) patients, mostly in patients with giant PHEO (26% vs 3%, P<.0001). Patients with giant PHEO had a longer hospital length of stay (laparoscopic: median 5 vs 2 days, P<.0001; open: median 6 vs 5 days, P=.24), and a higher complication rate (31% vs 10%, P=.006).Median follow up was 3 years (IQR 1-8) years, similar in patients and referents. Metastases developed at a much higher rate in patients with giant PHEOs (45% vs 4% in referents, P<.0001). Disease specific mortality was 7% in patients with giant PHEOs and 0% in referents. Conclusion: Patients with giant PHEO were more symptomatic, had a higher degree of catecholamine excess, and a higher rate of perioperative complications. Almost half of patients with giant PHEO developed metastases, warranting a close follow-up. Presentation: 6/2/2024

Abstract Context Data on giant pheochromocytomas (PHEOs), defined based on size 10 cm or greater, are scarce. Objective This work aimed to compare presentation, management, and outcomes of patients with giant vs non–giant PHEOs. Methods A retrospective cohort study was conducted in a referral center from 2000 to 2023. Consecutive patients with giant PHEOs and randomly chosen patients with non–giant PHEO (referents) were studied at a 1:6 ratio. Outcomes included perioperative complications, metastases, and mortality. Results Of 828 patients with PHEOs, 31 (3.7%) had giant PHEO (median size 12 cm, interquartile range [IQR] 10.0-13.5 cm). In comparison to referents (n = 186, median size 4 cm, IQR, 2.9-5.0 cm), patients with giant PHEO had more symptoms of catecholamine excess (median of 2 vs 1; P = .04) and presented with a higher prevalence of severe catecholamine excess (76% vs 30%; P < .0001). Adrenalectomy was performed in 94% of patients with giant PHEOs and 100% of referents. In addition to preoperative α-adrenergic blockade (89%), metyrosine was used in 14 (7%) patients, mostly in patients with giant PHEOs (26% vs 3%; P < .0001). Patients with giant PHEOs had a higher perioperative complication rate (31% vs 10%; P = .004). During a median follow-up of 3 years, metastases developed at a higher rate in patients with giant PHEOs (45% vs 4% in referents; P < .0001). Disease-specific mortality was 7% in patients with giant PHEOs and 0% in referents (P = .02). Conclusion Patients with giant PHEOs compared to referents were more symptomatic, had a higher degree of catecholamine excess, and had a higher rate of perioperative complications. Almost half of patients with giant PHEOs developed metastases, warranting close follow-up.

Introduction: Patients undergoing bariatric surgery with body mass index (BMI) >50 kg/m2 are at a higher risk of surgical morbidity when compared with less obese patients, however, there is limited data correlating surgical risk and efficacy with increasing BMI in patients with severe obesity. We hypothesize that regardless of the degree above 50 kg/m2 their BMI, patients with severe obesity respond similarly to bariatric surgery. Materials and Methods: We performed a retrospective analysis of patients with BMI >50 kg/m2 who underwent biliopancreatic diversion with duodenal switch, Roux-en-Y gastric bypass, or sleeve gastrectomy at a single institution. Outcomes were compared in patients with a BMI between 50 and 60 kg/m2 to patients with a BMI >60 kg/m2 and included percent total weight loss as well as early and late complications. Statistical analyses were performed using logistic regression, univariate, and multivariate models. Results: There were 571 patients with BMI >50 kg/m2 who underwent bariatric surgery at our center, 170 (29.8%) had a BMI >60 kg/m2. Percent total weight loss was statistically significant between the BMI 50 and 60 kg/m2 and BMI >60 kg/m2 groups at 24 months (P=0.047) but not at 60 months (P=0.54). No significant difference was found in the incidence of early complications in a univariate (P=0.46) or a multivariate (P=0.06) analysis. The BMI >60 subgroup was associated with a higher rate of late complications in univariate analysis (heart rate=2.37; 1.03-5.47, P=0.04), but not in multivariate analysis (P=0.78). Conclusions: Efficacy and complication rates of bariatric surgeries are similar in patients with BMI 50 to 60 kg/m2 and >60 kg/m2, providing evidence supporting similar management of patients despite specific subgroups.

Background To describe the effect of the COVID-19 pandemic on emergency general surgery operative volumes during governmental shutdowns secondary to the pandemic and characterize differences in disease severity, morbidity, and mortality during this time compared to previous years. Methods This retrospective cohort study compares patients who underwent emergency general surgery operations at a tertiary hospital from March 1st to May 31st of 2020 to 2019. Average emergent cases per day were analyzed, comparing identical date ranges between 2020 (pandemic group) and 2019 (control group). Secondary analysis was performed analyzing disease severity, morbidity, and mortality. Results From March 1st to May 31st, 2020, 2.5 emergency general surgery operations were performed on average daily compared to 3.0 operations on average daily in 2019, a significant decrease ( P = .03). No significant difference was found in presenting disease severity, morbidity, or mortality between the pandemic and control groups. Discussion This study demonstrates a decrease of 65% in emergency general surgery operations during governmental restrictions secondary to the COVID-19 pandemic. This decrease in operations was not associated with worse disease severity, morbidity, or mortality.

ABSTRACT Many viruses utilize cell adhesion molecules of the immunoglobulin superfamily as receptors. In particular, viruses of different classes exploit nectins. The large DNA viruses, herpes simplex and pseudorabies viruses, use ubiquitous nectins 1 and 2. The negative-strand RNA virus measles virus (MeV) uses tissue-specific nectin-4, and the positive-strand RNA virus poliovirus uses nectin-like 5 (necl-5), also known as poliovirus receptor. These viruses contact the BC, C′C″, and FG loops on the upper tip of their receptor's most membrane-distal domain. This location corresponds to the newly defined canonical adhesive interface of nectins, but how viruses utilize this interface has remained unclear. Here we show that the same key residues in the BC and FG loops of nectin-4 govern binding to the MeV attachment protein hemagglutinin (H) and cell entry, nectin-4 homodimerization, and heterodimerization with nectin-1. On the other hand, residues in the C′C″ loop necessary for homo- and heterotypic interactions are dispensable for MeV-induced fusion and cell entry. Remarkably, the C′C″ loop governs dissociation of the nectin-4 and H ectodomains. We provide formal proof that H can interfere with the formation of stable nectin-1/nectin-4 heterodimers. Finally, while developing an alternative model to study MeV spread, we observed that polarized primary pig airway epithelial sheets cannot be infected. We show that a single amino acid variant in the BC loop of pig nectin-4 fully accounts for restricted MeV entry. Thus, the three loops forming the adhesive interface of nectin-4 have different roles in supporting MeV H association and dissociation and MeV-induced fusion. IMPORTANCE Different viruses utilize nectins as receptors. Nectins are immunoglobulin superfamily glycoproteins that mediate cell-cell adhesion in vertebrate tissues. They interact through an adhesive interface located at the top of their membrane-distal domain. How viruses utilize the three loops forming this interface has remained unclear. We demonstrate that while nectin-nectin interactions require residues in all three loops, the association of nectin-4 with the measles virus hemagglutinin requires only the BC and FG loops. However, we discovered that residues in the C′C″ loop modulate the dissociation of nectin-4 from the viral hemagglutinin. Analogous mechanisms may support cell entry of other viruses that utilize nectins or other cell adhesion molecules of the immunoglobulin superfamily as receptors.