Comprehensive Genomic Characterization in Ovarian Low-Grade and chemosensitive and chemoresistant High-Grade Serous Carcinomas.

INTRODUCTION: Genomic characterization of serous ovarian carcinoma (SOC), which includes low-grade serous carcinoma (LGSC) and high-grade serous carcinoma (HGSC), remains necessary to improve efficacy of platinum-based chemotherapy. The aim was to investigate the genomic variations in these SOC groups, also in relation to chemoresponse. METHODS: 45 samples SOC were retrospectively analyzed by Next Generation Sequencing (NGS) on DNA/RNA extracts from formalin-fixed, paraffin-embedded (FFPE) tumor samples obtained at diagnosis. HGSCs were classified as platinum-resistant and platinum-sensitive. RESULTS: In the LGSC group, 44% of the carcinomas had mutually exclusive variants in the RAS/RAF pathway, while additional likely oncogenic variants in the CDKN2A, SMARCA4 and YAP1 genes were observed in the remaining LGSCs. Tumor mutation burden (TMB) was significantly lower in the intrinsically chemoresistant LGSC group than in the HGSC group. In the HGSC cohort, TP53 variants were found in 90% and homologous recombination repair (HRR) pathway variants in 41% of the neoplasms. HGSCs of the chemoresistant group without classic mutations in the HRR pathway were characterized by additional variants in FGFR2 and with a FGFR3::TACC3 fusion. In addition, HGSCs showed MYC, CCNE1 and AKT2 gains that were almost exclusively observed in the chemosensitive HGSC group. CONCLUSIONS: These results suggest that very low TMB and MYC, CCNE1 and AKT2 gains in SOC patients may be biomarkers related to platinum treatment efficacy. Thorough genomic characterization of SOCs prior to treatment might lead to more specific platinum-based chemotherapy therapy strategies.

Ocular Ischemic Syndrome and the Role of Carotid Artery Revascularization.

BACKGROUND: Ocular ischemic syndrome (OIS) is a rare presentation of atherosclerotic carotid artery stenosis that can result in permanent visual loss. This severely disabling syndrome remains under diagnosed and undertreated due to lack of awareness; especially since it requires expedited multidisciplinary care. The relevance of early diagnosis and treatment is increasing due to an increasing prevalence of cerebrovascular disease. METHODS: The long-term visual and cerebrovascular outcomes following intervention for nonarteritic OIS, remain poorly described and were the objective of this concise review. We conducted a PubMed search to include all English language publications (cohort studies and case reports) between 2002 and 2023. RESULTS: A total of 33 studies (479 patients) report the outcomes of treatment of OIS with carotid endarterectomy (CEA, 304 patients, 19 studies), and carotid artery stenting (CAS, 175 patients, 14 studies). Visual outcomes were improved or did not worsen in 447 patients (93.3%). No periprocedural stroke was reported. Worsening visual symptoms were rare (35 patients, 7.3%); they occurred in the immediate postoperative period secondary to ocular hypoperfusion (3 patients) and in the late postoperative period due to progression of systemic atherosclerotic disease. Symptomatic recurrence due to recurrent stenosis after CEA was reported in 1 patient (0.21%); this was managed successfully with CAS. None of these studies report the results of transcarotid artery revascularization, the long-term operative outcome or stroke rate. CONCLUSIONS: OIS remains to be an underdiagnosed condition. Early diagnosis and prompt treatment are crucial in reversal or stabilization of OIS symptoms. An expedited multidisciplinary approach between vascular surgery and ophthalmology services is necessary to facilitate timely treatment and optimize outcome. If diagnosed early, both CEA and CAS have been associated with visual improvement and prevention of progressive visual loss.

Midterm outcomes of endoscopic-assisted brachial-basilic arteriovenous fistula creation.

Endoscopic vein harvest remains underused in single-stage brachial-basilic arteriovenous fistula creation. We analyzed our results with the use of this technique in a cohort of predominantly obese (body mass index ≥30 kg/m2) patients. Demographics, intraoperative details, and outcomes for all consecutive patients who underwent single-stage endoscopic-assisted brachial-basilic arteriovenous fistula creation between 2020 and 2022 at a single institute were analyzed retrospectively. The primary outcomes were technical success, fistula maturation, and primary assisted and secondary patency rates. Of the 11 patients (7 men; mean age, 62 ± 11.6 years), 7 (64%) already required dialysis at referral. The mean body mass index was 34 ± 7 kg/m2, 64% were obese, and an additional 27% were overweight. The medical comorbidities included hypertension in 11 patients (100%), diabetes in 7 (64%), and smoking in 8 (73%). Technical success was 100%, with no intraoperative complications. The median procedural length was 231 minutes (range, 183-302 minutes). Early complications in two patients (18%) included bleeding of the venous side branch requiring ligation and the loss of thrill requiring division of a tethering bridge of a large tributary. The maturation rate was 100%, and the brachial-basilic arteriovenous fistula was successfully accessed in all patients who required dialysis. At 12 months, the primary assisted and secondary patency rates were 90% ± 10% and 100%, respectively. Reintervention in seven patients (64%) included successful angioplasty in four, thrombectomy in two, and aneurysm resection with an interposition graft in one patient. Endoscopic vein harvest can be used for single-stage brachial-basilic arteriovenous fistula creation with good technical success and favorable maturation and patency rates, even for obese patients.

Outcomes of Arterial Bypass With the Human Acellular Vessel for Chronic Limb-Threatening Ischemia Performed Under the FDA Expanded Access Program.

OBJECTIVE: To report outcomes of the human acellular vessel (HAV) implanted for limb salvage through the Food and Drug Administration (FDA) Expanded Access Program for patients with chronic limb-threatening ischemia with no autologous conduit. METHODS: The HAV is a bioengineered vascular conduit designed with human vascular smooth muscle cells. The product is under regulatory study. From April 2019 to November 2021, the HAV was implanted in 14 patients (12 men; mean age, 62±14 years) at 3 US centers. Each case was performed with a single-use investigational new drug Expanded Access Program issued by the FDA. Institutional review board approval was obtained; technical and clinical outcomes were analyzed. RESULTS: A single 6-mm-diameter (40-cm-long) HAV was implanted in 9 patients; 5 patients required 2 HAVs sewn together as a composite. Technical success was 100%. Median follow-up was 12 (range, 1 to 41) months. Primary and secondary patency rates were 72% and 81% at 12 months; assisted primary patency was attained in 4 patients. Amputation-free survival was 93% at 6 months and 77% at 12 months. All patients with a patent HAV experienced clinical improvement with no HAV-related infections or adverse events. There were 4 deaths in the cohort, late mortality unrelated to the HAV. CONCLUSION: The HAV is a safe and effective "off-the-shelf" biologic conduit. This experience from the FDA Expanded Access Program in this population with few alternative limb salvage options will help guide regulatory deliberations for patients with lower extremity ischemia and no autologous bypass conduit options.

Outcomes of lower extremity arterial bypass using the Human Acellular Vessel in patients with chronic limb-threatening ischemia.

OBJECTIVE: Patients with chronic limb-threatening ischemia (CLTI) and no great saphenous vein to use as a conduit for arterial bypass have a high risk for amputation despite advances in medical and endovascular therapies. This report presents findings from a U.S. Food and Drug Administration (FDA) supported study of the Human Acellular Vessel (HAV) (Humacyte Inc.) used as a conduit for arterial bypass in patients with CLTI and inadequate or absent autologous conduit. METHODS: The HAV is a 6-mm, 40-cm vessel created from human vascular smooth muscle cells seeded onto a polyglycolic acid scaffold pulsed in a bioreactor for 8 weeks as cells proliferate and the scaffold dissolves. The resultant vessel is decellularized, creating a nonimmunogenic conduit composed of collagen, elastin, and extracellular matrix. The FDA issued an Investigational New Drug for an intermediate-sized, single-center study of the HAV under the agency's Expanded Access Program in patients with advanced CLTI and inadequate or absent autologous conduit. Technical results and clinical outcomes were analyzed and reported. RESULTS: Between March 2021 and July 2023, 29 patients (20 males; mean age, 71 ± 11 years) underwent limb salvage operation using the HAV as a bypass conduit. Most patients had advanced CLTI (Rutherford class 5/6 in 72%; wound, ischemia, and foot infection stage 3/4 in 83%), and 97% had previously failed revascularization(s) of the extremity. Two HAVs were sewn together to attain the needed bypass length in 24 patients (83%). Bypasses were to tibial arteries in 23 patients (79%) and to the popliteal artery in 6 (21%). Technical success was 100%, and the 30-day mortality rate was 7% (2 patients). With 100% follow-up (median, 9.3 months), the limb salvage rate was 86% (25/29 patients). There were 16 reinterventions to restore secondary patency, of which 15 (94%) were successful. Primary and secondary patency of the HAV at 9 months were 59% and 71%, respectively. CONCLUSIONS: The HAV has demonstrated short- to intermediate-term safety and efficacy as an arterial bypass conduit in a complex cohort of patients with limb-threatening ischemia and no autologous options. This experience using the FDA's Expanded Access Program provides real-world data to inform regulatory deliberations and future trials of the HAV, including the study of the vessel as a first-line bypass conduit in less severe cases of chronic limb ischemia.

The Human Acellular Vessel (HAV) as a vascular conduit for infrainguinal arterial bypass.

Autologous vein is the optimal conduit for peripheral arterial bypass surgery, a standard recently highlighted by findings from the BEST-CLI trial. The Human Acellular Vessel is a novel biologic conduit produced using regenerative medicine technologies with structural and mechanical properties like a human blood vessel. Not yet approved by the United States Food and Drug Administration, the Human Acellular Vessel is being studied as an alternative bypass conduit in patients with peripheral arterial disease, vascular injury, and those in need of arteriovenous access for hemodialysis. This report describes and illustrates the technical aspects of intraoperative handling specific to the use of this new and innovative technology.

International Union of Angiology consensus document on vascular compression syndromes.

Vascular compression syndromes (VCS) are rare diseases, but they may cause significant symptoms interfering with the quality of life (QoL) of patients who are often in their younger age. Given their infrequent occurrence, multiform clinical and anatomical presentation, and absence of dedicated guidelines from scientific societies, further knowledge of these conditions is required to investigate and treat them using modern imaging and surgical (open or endovascular) techniques. This consensus document will focus on known VCS, affecting the arterial and venous system. The position paper, written by members of International Union of Angiology (IUA) Youth Committee and senior experts, will show an overview of pathophysiology, diagnostic, and therapeutical approaches for patients with VCS. Furthermore, this document will provide also unresolved issues that require more research that need to be addressed in the future.

Results of a Flexible Patient-Centered Approach to the Timing of Thoracic Outlet Decompression in Paget Schroetter Syndrome.

BACKGROUND: Treatment algorithms for subclavian vein (SCV) effort thrombosis (Paget-Schroetter syndrome- PSS) are multiple, ranging from thrombolysis (TL) with immediate or delayed thoracic outlet decompression (TOD) to conservative treatment with anticoagulation alone. We follow a regimen of TL/pharmacomechanical thrombectomy (PMT) followed by TOD with first rib resection, scalenectomy, venolysis, and selective venoplasty (open or endovascular) performed electively at a time convenient for the patient. Oral anticoagulants are prescribed for 3 months or longer based upon response. The aim of this study was to evaluate outcomes of this flexible protocol. METHODS: Clinical and procedural details of consecutive patients treated for PSS from January 2001 to August 2016 were retrospectively reviewed. Endpoints included success of TL and eventual clinical outcome. Patients were divided into 2 groups-Group I: TL/PMT + TOD; Group II: medical management/anticoagulation + TOD. RESULTS: PSS was diagnosed in 114 patients; 104 (62 female, mean age 31 years) who underwent TOD were included in the study. Group I: 53 patients underwent TOD after initial TL/PMT (23 at our institution and 30 elsewhere) with success (acute thrombus resolution) in 80% (n = 20) and 72% (n = 24) respectively. Adjunctive balloon-catheter venoplasty was performed in 67%. TL failed to recanalize the occluded SCV in 11% (n = 6). Complete thrombus resolution was seen in 9% (n = 5). Residual chronic thrombus in 79% (n = 42) resulted in median SCV stenosis of 50% (range 10% to 80%). With continued anticoagulation, further thrombus retraction was noted with median 40% improvement in stenosis including in veins with unsuccessful TL. TOD was performed at a median of 1.5 months (range 2-8 months). Rethrombosis of the SCV occurred in 3 patients 1-3 days postoperatively and was managed with MT/SCV stenting/balloon angioplasty and anticoagulation. Symptomatic relief was achieved in 49/53 (92%) patients at a median follow-up of 14 months. Group II: 51 patients underwent TOD following medical treatment elsewhere with anticoagulation alone for an average 6 months (range 2-18 months) with recurrent SCV thrombosis in 5 (11%). Thirty-nine patients (76%) had persistent symptoms; the remaining had asymptomatic compression of the SCV with maneuvers. SCV occlusion persisted in 4 patients (7%); the indication for TOD being residual symptoms from compression of collateral veins, the median residual stenosis was 70% (range 30-90%). TOD was performed at a median of 6 months after diagnosis of PSS. Open venous reconstruction with endovenectomy and patch was performed in 4 patients and stenting in 2. Symptomatic relief was achieved in 46/51 (90%) at a median follow-up of 24 months. CONCLUSIONS: For Paget Schroetter syndrome a management protocol encompassing elective thoracic outlet decompression at a convenient time following thrombolysis is safe and effective, with low risk of rethrombosis. Continued anticoagulation in the interim results in further recanalization of the subclavian vein and may reduce the need for open venous reconstruction.

An expeditious and precise method for diameter reduction of venous aneurysm causing arteriovenous fistula steal syndrome.

Clinically significant dialysis access steal syndrome occurs in 1% to 8% of patients. In the present report, we describe an innovative, hybrid option for venoplasty of a cephalic vein aneurysm using a vascular staple device in conjunction with a 6-mm, endovascular balloon placed a few centimeters distal to the brachial artery anastomosis in a 61-year-old man with stage 3 dialysis access steal syndrome secondary to overwhelming venous outflow. The patient experienced immediate postoperative symptom relief. The arteriovenous fistula was immediately accessible for dialysis, circumventing the need for a temporary dialysis catheter. The arteriovenous fistula was functional at 12 months of follow-up.

Flap management of groin wounds following vascular procedures: A review of 270 flaps for vascular salvage.

BACKGROUND: Groin dehiscence following vascular procedures results in morbidity for patients with peripheral vascular disease. Controversy exists around the indications for flap coverage. We present an institutional experience with flap reconstruction of groin wounds after vascular procedures to identify predictors of beneficial outcomes. PATIENTS AND METHODS: A retrospective review of patients who had flap coverage for infected/nonhealing groin wounds following a vascular procedure between 1998 and 2021 was performed. Demographics and clinical characteristics, including flap and vascular graft type, were collected along with major complications. Univariate and multivariable logistic regression analyses were performed to assess the associations between procedures and major complications. RESULTS: A total of 270 flaps were transferred to 237 patients. Thirty-three patients had bilateral wounds. The mean age and BMI were 67 ± 11 years and 27.9 ± 6.3 kg/m2, respectively. Flaps included rectus femoris (n = 142), sartorius (n = 118), rectus abdominis (n = 7), and gracilis (n = 3). Covered vascular grafts included prosthetic materials (n = 200) and autografts (n = 70). The median length of hospital stay after surgery was 10 days (interquartile range=12), and the mean follow-up was 29.1 ± 39.2 months. The major complication rate was 38.5% with wound infection being the most common. Flaps successfully prevented the infection-related removal of the grafts in 98.9% of cases. Multivariable analysis revealed no significant associations between variables and having a major complication. CONCLUSIONS: Flap coverage of the inguinal vessels can be performed safely with favorable limb salvage. Wound complications were high, but graft salvage was excellent. Rectus femoris and sartorius muscle flaps were the most common flaps, yielding comparable outcomes.

Clinical presentation, operative management, and long-term outcomes of rupture after previous abdominal aortic aneurysm repair.

OBJECTIVE: The aim of the present study was to evaluate the presentation trends, intervention, and survival of patients who had been treated for late abdominal aortic aneurysm rupture (LAR) after open repair (OR) or endovascular aortic aneurysm repair (EVAR). METHODS: We reviewed the clinical data from a single-center, retrospective database for patients treated for LAR from 2000 to 2020. The end points were the 30-day mortality, major postoperative complication, and survival. The outcomes between LAR managed with EVAR (group I) vs OR were compared (group II). RESULTS: Of 390 patients with infrarenal aortic rupture, 40 (10%) had experienced aortic rupture after prior aortic repair and comprised the LAR cohort (34 men; age 78 ± 8 years). LAR had occurred before EVAR in 30 and before OR in 10 patients. LAR was more common in the second half of the study with 32 patients after 2010. LAR after prior OR was secondary to ruptured para-anastomotic pseudoaneurysms. After initial EVAR, LAR had occurred despite reintervention in 17 patients (42%). The time to LAR was shorter after prior EVAR than after OR (6 ± 4 vs 12 ± 4 years, respectively; P = .003). Treatment for LAR was EVAR for 25 patients (63%; group I) and OR for 15 (37%, group II). LAR after initial OR was managed with endovascular salvage for 8 of 10 patients. Endovascular management was more frequent in the latter half of the study period. In group I, fenestrated repair had been used for seven patients (28%). Salvage for the remaining cases was feasible with EVAR, aortic cuffs, or limb extensions. The incidence of free rupture, time to treatment, 30-day mortality (8% vs 13%; P = .3), complications (32% vs 60%; P = .1), and disposition were similar between the two groups. Those in group I had had less blood loss (660 vs 3000 mL; P < .001) and less need for dialysis (0% vs 33%; P < .001) than those in group II. The median follow-up was 21 months (interquartile range, 6-45 months). The overall 1-, 3-, and 5-year survival was 76%, 52%, and 41%, respectively, and was similar between groups (28 vs 22 months; P = .48). Late mortality was not related to the aorta. CONCLUSIONS: LAR after abdominal aortic aneurysm repair has been encountered more frequently in clinical practice, likely driven by the frequency of EVAR. However, most LARs, including those after previous OR, can now be salvaged with endovascular techniques with lower morbidity and mortality.

An Analysis of Malpractice Litigation of Vascular Surgeons in Cases Involving Aortic Pathologies.

OBJECTIVE: The aim of this study was to analyze malpractice claims for aortic pathologies and to assess if there has been a change in rate of malpractice lawsuits with evolution of endovascular therapy. METHODS: Malpractice lawsuits were individually screened and compiled from the Westlaw database from 2000 to 2017 through use of relevant search terms. Data were collected of allegations, diagnoses, and outcomes of each case and compared. RESULTS: 268 unique cases were included in this study, with aneurysms (54%, n = 145) and dissection (35%, n = 94) making up the majority. There was a defendant verdict in 53% (n = 141), plaintiff verdict in 24% (n = 65), and settlements in 23% (n = 62) of lawsuits. Litigation was higher in the Midwest and Northeast. There was a gradual decline in litigation overall, however endovascular case numbers remained constant. There was negligible difference in the primary allegation underlying the litigation for various aortic pathologies, time to litigation and award between open and endovascular procedures. CONCLUSION: The proportion of litigation for clinical negligence in endovascular cases amongst all vascular surgical lawsuits is increasing. As novel methods of endovascular therapy emerge, it is imperative that physicians remain vigilant to legal considerations to minimize malpractice risk.

Interventions for superior vena cava syndrome.

Superior vena cava (SVC) syndrome refers to the clinical manifestations of cerebral venous hypertension secondary to obstruction of the SVC and/or the innominate veins. The most common cause of SVC syndrome is malignancy like small cell lung cancer and non-Hodgkin lymphoma, but there is an increasing trend of benign etiologies secondary to thrombosis due to central lines/ pacemakers or mediastinal fibrosis. Supportive measures include head elevation, diuresis, supplemental oxygen, and steroids. Thrombolysis with or without endovenous stenting is required emergently in those with airway compromise or symptoms secondary to cerebral edema. Definitive treatment in those with malignancy is multidisciplinary; this requires radiotherapy, chemotherapy, SVC stenting, oncologic surgery and SVC bypass or reconstruction. Endovascular treatment is the primary modality for palliation in malignancy and in those with benign etiology. Surgery is reserved for those who have failed or are unsuitable for endovascular treatment. In patients with benign disease endovenous stenting and open surgery provide excellent symptom relief and are safe and effective.

International Union of Angiology Position Statement on no-option chronic limb threatening ischemia.

This position paper, written by members of International Union of Angiology (IUA) Youth Committee and senior experts, shows an overview of therapeutical approaches for patients with chronic limb-threatening ischemia (CLTI) and absence of 'standard' solutions for revascularization. The aim was to demonstrate the accurate management of the 'no-option' CLTI patient including the wound treatment and the rehabilitation, considering always the goal of the increase of quality of life of the patients.