Risk, prevention, screening and management of carotid artery stenosis in head & neck cancer patients-An evidence based review.

Our review aims to clarify the incidence of carotid artery stenosis, risks of development, screening, management, and primary prevention strategies documented in the literature after radiation therapy for head and neck cancers. The high prevalence of carotid stenosis after radiation therapy for head and neck cancers has made surveillance and risk stratification critical. In addition to general cardiovascular risk factors such as smoking, diabetes, and dyslipidemia, risk factors for carotid artery stenosis after head and neck radiation included total plaque score, radiotherapy use and dosage, length of time after radiotherapy, and age greater than 50. Cancer subtype, namely nasopharyngeal cancer, may be correlated with increased risk as well, though contrasting results have been found. Interestingly, however, no significant relationship has been found between radiotherapy dose and stroke risk. Surgical management of post-radiation carotid stenosis is similar to that of stenosis unrelated to radiation, with carotid endarterectomy considered to be the gold standard treatment and carotid artery stenting being an acceptable, less-invasive alternative. Medical management of these patients has not been well-studied, but antiplatelet therapy, statins, and blood pressure control may be beneficial. The mainstay of screening for radiation-induced stenosis has been Doppler ultrasound, with measurement of changes in the intima-media thickness being a primary marker of disease development. A literature review was carried out using the MeSH terms "Carotid Artery Stenosis," "Head and Neck Neoplasms," and "Radiotherapy."

Multi-Level Thrombotic/Embolic Burden and Its Role in Sex-Related Outcomes in Acute Limb Ischemia (ALI).

INTRODUCTION: The impact of sex upon outcomes in acute limb ischemia (ALI) remains disputed. We aim to quantify the effect of sex upon amputation-free survival (AFS) after a percutaneous-first approach for ALI. METHODS: Two-center retrospective review of ALI managed via a percutaneous-first approach. Demographics, comorbidities, and clinical characteristics were analyzed (Table I). The Kaplan-Meier and Cox regression were used to estimate AFS, limb-salvage and overall survival. RESULTS: Over nine years, 170 patients (87, 51% males; median age 67 IQR 59, 77 years) presented with ALI. Rutherford Classification was I in 56 (33%); IIa in 85 (50%); IIb in 20 (12%) and III in 9 (5%). Thirty-day mortality, major amputation rate and fasciotomy rates were 8% (N=13); 6.5% (N=11), and 4.7% (N=8), respectively. Among revascularized limbs, 92% were patent at 30 days. Length of stay was 7 (IQR 3-11) days. Complications included 13 bleeding episodes (8%), 4 cases of atrial fibrillation (2%), and 3 re-thrombosis/clot extension events (1.7%). No differences were noted in complication rates when stratified by sex. Females were older than males (median age 70 IQR 62, 79 vs 65 IQR 56, 76 years; p=0.02) and more likely to present with atrial fibrillation (20.5% vs 8%, p 0.02); and hyperlipidemia (72% vs 57%, p = 0.04). Females also more frequently presented with multi-level thrombotic/embolic burden compared to males (56% vs 43%; p=0.03), and required both aspiration thrombectomy and thrombolysis (27% versus 14%; p 0.02). Kaplan-Meier estimated median AFS, limb salvage, and overall survival were 425 (IQR 140, 824 days); 314 (IQR 72, 727 days); and 342 (IQR 112, 762 days). When stratified by sex, females had worse survival (median 270 IQR 92, 636 versus 406 IQR 140, 937 days; p=0.005); and limb salvage (median 241 IQR 88, 636 versus 363 IQR 49, 822 days; p=0.04) compared to males. Univariate Cox regression showed female sex (HR = 1.46 95% CI 1.04-2.05; p=0.03); multi-level thrombotic/embolic burden (HR 1.64 95% CI 1.17-2.31; p=0.004) and Rutherford Class (HR 1.37 95% CI 1.08-1.73; p=0.009) predicted major amputation/death. By multivariable Cox regression, multi-level thrombotic/embolic burden (HR 1.54 95% CI 1.09-2.17; p=0.01), Rutherford Class (HR 1.34 95% CI 1.07-1.69; p=0.01), and female Sex (HR = 1.45 95% CI 1.03-2.05; p=0.03) were each independently predictive of major amputation/death. CONCLUSIONS: A percutaneous-first strategy is safe and efficacious in the overall ALI population. Similar to prior works, female versus male ALI patients in our cohort have higher rates of mortality and major amputation. In our multivariable model, multi-level thrombotic/embolic burden was independently associated with a greater than 45% increased hazard of major amputation/ death at last follow up. Further prospective analysis is warranted to elucidate the underlying factors contributing to the higher prevalence of multi-level thrombotic/embolic burden in female ALI patients, and to further define the optimal percutaneous-first approach for ALI in consideration of patient sex and extent of clot burden.

Creation of EGD-Derived Gastric Cancer Organoids to Predict Treatment Responses.

Gastric adenocarcinoma (GAd) is the third leading cause of cancer-related deaths worldwide. Most patients require perioperative chemotherapy, yet methods to accurately predict responses to therapy are lacking. Thus, patients may be unnecessarily exposed to considerable toxicities. Here, we present a novel methodology using patient-derived organoids (PDOs) that rapidly and accurately predicts the chemotherapy efficacy for GAd patients. Methods:Endoscopic GAd biopsies were obtained from 19 patients, shipped overnight, and PDOs were developed within 24 h. Drug sensitivity testing was performed on PDO single-cells with current standard-of-care systemic GAd regimens and cell viability was measured. Whole exome sequencing was used to confirm the consistency of tumor-related gene mutations and copy number alterations between primary tumors, PDOs, and PDO single-cells. Results:Overall, 15 of 19 biopsies (79%) were appropriate for PDO creation and single-cell expansion within 24 h of specimen collection and overnight shipment. With our PDO single-cell technique, PDOs (53%) were successfully developed. Subsequently, two PDO lines were subjected to drug sensitivity testing within 12 days from initial biopsy procurement. Drug sensitivity assays revealed unique treatment response profiles for combination drug regimens in both of the two unique PDOs, which corresponded with the clinical response. Conclusions:The successful creation of PDOs within 24 h of endoscopic biopsy and rapid drug testing within 2 weeks demonstrate the feasibility of our novel approach for future applications in clinical decision making. This proof of concept sets the foundation for future clinical trials using PDOs to predict clinical responses to GAd therapies.

Cloud-based fusion imaging improves operative metrics during fenestrated endovascular aneurysm repair.

OBJECTIVE: Endovascular treatment of complex aortic pathology has been associated with increases in procedural-related metrics, including the operative time and radiation exposure. Three-dimensional fusion imaging technology has decreased the radiation dose and iodinated contrast use during endovascular aneurysm repair. The aim of the present study was to report our institutional experience with the use of a cloud-based fusion imaging platform during fenestrated endovascular aneurysm repair (FEVAR). METHODS: A retrospective review of a prospectively maintained aortic database was performed to identify all patients who had undergone FEVAR with commercially available devices (Zenith Fenestrated; Cook Medical Inc, Bloomington, IN) between 2013 and 2020 and all endovascular aneurysm repairs performed using Cydar EV Intelligent Maps (Cydar Medical, Cambridge, UK). The Cydar EV cohort was reviewed further to select all FEVARs performed with overlay map guidance. The patient demographic, clinical, and procedure metrics were analyzed, with a comparative analysis of FEVAR performed without and with the Cydar EV imaging platform. Patients were excluded from comparative analysis if the data were incomplete in the dataset or they had a documented history of prior open or endovascular abdominal aortic aneurysm repair. RESULTS: During the 7-year study period, 191 FEVARs had been performed. The Cydar EV imaging platform was implemented in 2018 and used in 124 complex endovascular aneurysm repairs, including 69 consecutive FEVARs. A complete dataset was available for 137 FEVARs. With exclusion to select for de novo FEVAR, a comparative analysis was performed of 53 FEVAR without and 63 with Cydar EV imaging guidance. The cohorts were similar in patient demographics, medical comorbidities, and aortic aneurysm characteristics. No significant difference was noted between the two groups for major adverse postoperative events, length of stay, or length of intensive care unit stay. The use of Cydar EV resulted in nonsignificant decreases in the mean fluoroscopy time (69.3 ± 28 minutes vs 66.2 ± 33 minutes; P = .598) and operative time (204.4 ± 64 minutes vs 186 ± 105 minutes; P = .278). A statistically significant decrease was found in the iodinated contrast volume (105 ± 44 mL vs 83 ± 32 mL; P = .005), patient radiation exposure using the dose area product (1,049,841 mGy/cm2 vs 630,990 mGy/cm2; P < .001) and cumulative air kerma levels (4518 mGy vs 3084 mGy; P = .02) for patients undergoing FEVAR with Cydar EV guidance. CONCLUSIONS: At our aortic center, we have observed a trend toward shorter operative times and significant reductions in both iodinated contrast use and radiation exposure during FEVAR using the Cydar EV intelligent maps. Intelligent map guidance improved the efficiency of complex endovascular aneurysm repair, providing a safer intervention for both patient and practitioner.

Outcomes after inferior vena cava thrombectomy and reconstruction for advanced renal cell carcinoma with tumor thrombus.

BACKGROUND: This report details the experience of a multidisciplinary surgical team in the management of stage III and stage IV renal cell carcinoma (RCC) with concomitant inferior vena cava (IVC) tumor thrombus. METHODS: A retrospective inquiry of our vascular database from 2003 to 2012 identified 55 surgical cases of stage III (n = 40) and stage IV (n = 15) RCC presenting with IVC tumor thrombus. Tumor characteristics and IVC tumor thrombus were evaluated by clinical staging and postoperative pathology staging. Patient demographics and surgical reconstruction are detailed. Cancer-specific outcomes consisted of oncologic surveillance with computed tomography or magnetic resonance imaging. A Clavien-Dindo classification of early (<30 days) complications and mortality was recorded, including a review of secondary surgical interventions. RESULTS: According to the Novick classification of IVC tumor thrombus, there were 10 supradiaphragmatic (level IV), 20 intrahepatic (level III), and 25 infrahepatic (level II or I) tumor thrombi. Vena cava reconstruction was completed in 54 patients (98%), with one patient deemed unresectable. Vena cava control required cardiac bypass (n = 10), venovenous bypass (n = 4), or infrahepatic IVC control (n = 40). Reconstruction of the IVC was completed with two prosthetic interposition grafts for one stage IV thrombus and one stage III thrombus; two patch repairs were done for stage III thrombus, and there were 50 primary IVC repairs. All other IVC reconstructions were patent at a mean follow-up of 23 months. A single asymptomatic patient with primary IVC repair had estimated 30% IVC narrowing but no other measurable stenosis as detected by postoperative imaging. Three patients required reoperation (two for surgical site bleeding, one for small bowel fistula). Early surgical complications included Clavien-Dindo grades I (n = 3), II (n = 6), IIIa (n = 2), IIIb (n = 3), and V (n = 2). Regional retroperitoneal or distant recurrent RCC occurred in 26 patients (48%); a single patient demonstrating recurrent IVC tumor thrombus at 8 months required secondary IVC thrombectomy. All patients with tumor invasion of the IVC wall developed recurrent RCC, and no patient survived beyond 5 years. Early mortality was 3.6% (n = 2), with 27 patients (49%) dying within 24 months, resulting in an overall mortality for the cohort of 80% (n = 44) as established on routine regular postoperative surveillance. CONCLUSIONS: A multidisciplinary approach for the management of advanced RCC and IVC tumor thrombus helps optimize outcomes. Primary IVC repairs are possible in most patients, and IVC patency is good. Recurrent tumor thrombus rates are low; however, RCC tumor recurrence and mortality are high, especially among patients with advanced cancer with IVC wall invasion.

Thoracic endovascular repair as a safe management strategy for aortobronchial fistulas.

OBJECTIVES: This study assessed the safety and efficacy of thoracic endovascular aortic repair (TEVAR) in the management of aortobronchial fistulas. METHODS: A retrospective review was performed at Emory University Hospital to identify all patients who presented with an aortobronchial fistula. The diagnosis was based on clinical, radiologic, and bronchoscopic findings. Patients who underwent TEVAR as definitive management of these fistulas were identified. Demographics, history of thoracic aorta pathology or intervention, type and number of endografts used, need for reoperation, and clinical and radiologic follow-up data were collected for each individual. RESULTS: Between 2000 and 2009, 11 patients received TEVAR as definitive management of aortobronchial fistulas. Technical success was achieved in 10 patients (91%). Six patients (55%) had previously undergone thoracic aortic surgery. A proximal type 1 endoleak developed in one patient after graft deployment and required reintervention for additional graft placement. No intraoperative or 30-day deaths occurred. Postoperative clinical and radiographic assessment was a mean of 8.8 months (range, 1-40 months). For all 10 patients in whom technical success was achieved at the initial operation, no endoleaks were noted at the follow-up CT scan. In addition, no patient required a further intervention. CONCLUSIONS: This study represents the largest reported series on the use of TEVAR in the management of aortobronchial fistulas. Supported by postoperative surveillance imaging and clinical evaluation, TEVAR has proven to be a safe and effective management strategy for an otherwise lethal condition. Long-term follow-up data are needed to ascertain the durability of this approach.