Histological Changes in the Popliteal Artery Wall in Patients with Critical Limb Ischemia.

INTRODUCTION: This prospective study aims to illustrate the histopathological arterial changes in the popliteal artery in peripheral arterial disease of the lower limbs. MATERIAL AND METHOD: A total of 60 popliteal artery segments taken from patients who had undergone lower limb amputation were examined between April and June 2023. The degree of arterial stenosis, medial calcinosis, and the vasa vasorum changes in the arterial adventitia were quantified. The presence of risk factors for atherosclerosis was also observed. RESULTS: Atherosclerotic plaque was found in all of the examined segments. Medial calcinosis was observed in 40 (66.6%) of the arterial segments. A positive association between the degree of arterial stenosis and the vasa vasorum changes in the arterial adventitia was also found (p = 0.025). The level of blood sugar and cholesterol were predictive factors for the severity of atherosclerosis. CONCLUSIONS: Atherosclerosis and medial calcinosis are significant in patients who underwent lower limb amputation. Medial calcinosis causes damage to the arterial wall and leads to a reduction in responsiveness to dilator stimuli.

Extracranial Vascular Anomalies Driven by RAS/MAPK Variants: Spectrum and Genotype-Phenotype Correlations.

BACKGROUND: We aimed to correlate alterations in the rat sarcoma virus (RAS)/mitogen-activated protein kinase pathway in vascular anomalies to the clinical phenotype for improved patient and treatment stratification. METHODS AND RESULTS: This retrospective multicenter cohort study included 29 patients with extracranial vascular anomalies containing mosaic pathogenic variants (PVs) in genes of the RAS/mitogen-activated protein kinase pathway. Tissue samples were collected during invasive treatment or clinically indicated biopsies. PVs were detected by the targeted sequencing of panels of genes known to be associated with vascular anomalies, performed using DNA from affected tissue. Subgroup analyses were performed according to the affected genes with regard to phenotypic characteristics in a descriptive manner. Twenty-five vascular malformations, 3 vascular tumors, and 1 patient with both a vascular malformation and vascular tumor presented the following distribution of PVs in genes: Kirsten rat sarcoma viral oncogene (n=10), neuroblastoma ras viral oncogene homolog (n=1), Harvey rat sarcoma viral oncogene homolog (n=5), V-Raf murine sarcoma viral oncogene homolog B (n=8), and mitogen-activated protein kinase kinase 1 (n=5). Patients with RAS PVs had advanced disease stages according to the Schobinger classification (stage 3-4: RAS, 9/13 versus non-RAS, 3/11) and more frequent progression after treatment (RAS, 10/13 versus non-RAS, 2/11). Lesions with Kirsten rat sarcoma viral oncogene PVs infiltrated more tissue layers compared with the other PVs including other RAS PVs (multiple tissue layers: Kirsten rat sarcoma viral oncogene, 8/10 versus other PVs, 6/19). CONCLUSIONS: This comparison of patients with various PVs in genes of the RAS/MAPK pathway provides potential associations with certain morphological and clinical phenotypes. RAS variants were associated with more aggressive phenotypes, generating preliminary data and hypothesis for future larger studies.

Radiofrequency Thermal Ablation for the Treatment of Chronic Insufficiency of the Saphenous Vein-A Comparative Retrospective Study.

OBJECTIVES: The broad spectrum of chronic venous disease encompasses varicose veins, edema, hyperpigmentation and venous ulcers. Radiofrequency thermal ablation is indicated for the treatment of superficial venous reflux of the lower limb. Our research is a comparative clinical study that aims to identify the most effective and safest therapeutic method in the management of chronic venous insufficiency of the lower limbs. MATERIALS AND METHODS: Patients admitted to the Department of Surgery of the University of Medicine and Pharmacy in Cluj-Napoca, Romania, with the clinical diagnosis of varicose veins of the lower limbs, treated by thermal ablation with radiofrequency or by open surgical techniques during the year 2022, were included. RESULTS: A percentage of 50.9% of the patients were treated by the radiofrequency thermal ablation procedure and 49.1% by surgical treatment. More than half of them were hospitalized for 2 days. The duration of hospitalization was significantly longer in patients who had postoperative complications (p < 0.001). The chance of being treated by open surgical treatment for a small saphenous vein is 10.11 times higher than by radiofrequency thermal ablation. CONCLUSION: According to the applied tests, there is no statistical difference between the group treated by radiofrequency thermal ablation and the one surgically treated in terms of sex, age, origin, CEAP clinical stage at hospitalization, clinical diagnosis at hospitalization and affected lower limb.

Individualized treatment of congenital vascular malformations of the tongue.

BACKGROUND/OBJECTIVE: Oral malformations of the tongue are exceedingly rare. The aim of this study was to evaluate the effectiveness of individualized treatment for patients with vascular malformations of the tongue. METHODS: This retrospective study is based on a consecutive local registry at a tertiary care Interdisciplinary Center for Vascular Anomalies. Patients with vascular malformations of the tongue were included. Indications for therapy of the vascular malformation were macroglossia with the impossibility to close the mouth, bleeding, recurrent infection and dysphagia. Size regression of the malformation (volume measurement) and symptom improvement were investigated. RESULTS: Out of 971 consecutive patients with vascular malformations, 16 patients suffered from a vascular malformation of the tongue. Twelve patients had slow-flow malformations and 4 fast-flow malformations. Indications for interventions were bleeding (4/16, 25%), macroglossia (6/16, 37.5%), and recurrent infections (4/16, 25%). For two patients (2/16, 12.5%), there was no indication for intervention due to absence of symptoms. Four patients received sclerotherapy, 7 patients Bleomycin-electrosclerotherapy (BEST) and 3 patients embolization. Median follow-up was 16 months (IQR 7-35.5). In all patients, symptoms had decreased after two interventions at a median (IQR 1-3.75). Volume reduction of the malformation of the tongue was 13.3% (from median 27.9 cm3 to median 24.2 cm3, p = 0.0039), and even more pronounced when considering only patients with BEST (from 86 cm3 to 59.1 cm3, p = 0.001). CONCLUSION: Symptoms of vascular malformations of the tongue are improved after a median of two interventions with significantly increased volume reduction after Bleomycin-electrosclerotherapy.

Towards a better treatment of patients with vascular malformations: certified interdisciplinary centers are mandatory.

BACKGROUND: Vascular anomalies are orphan diseases that occur in all age groups and range from purely aesthetic to potentially life-threatening conditions. This thesis paper outlines the typical conferring problems in patient management and possible structural solutions for a better patient treatment in the future. METHODS: A multi-perspective author panel consisting of key stakeholders from the German Interdisciplinary Society of Vascular Anomalies and the German Society for Surgery defined problem areas and possible solutions including quality indicators as criteria for certified interdisciplinary Vascular Anomalies Centers (VAC). RESULTS: According to the literature available, clearly defined nomenclature and nosological entities often remain unused in this field, and consented diagnostic and therapeutic evidence is rare. Expert opinions dominate and in some cases lead to disparate recommendations. Typical patient problems arise from this situation, exemplified in patient vignettes. Centralized and standardized patient treatment in interdisciplinary VAC may be a solution to this problem. These centers should agree on a set of general principles and quality indicators with an additional minimum set of structural and procedural criteria. DISCUSSION: The present position paper outlines perspectives for implementing certified interdisciplinary VAC. There is a need for a comprehensive nomenclature, access to interdisciplinary treatment centers, more scientific evidence, and further education in this rare group of diseases. CONCLUSION: Use of scientifically sound and patient-relevant criteria for certifying the interdisciplinary quality of VAC is expected to improve health care in Germany.

Imaging of peripheral vascular malformations - current concepts and future perspectives.

Vascular Malformations belong to the spectrum of orphan diseases and can involve all segments of the vascular tree: arteries, capillaries, and veins, and similarly the lymphatic vasculature. The classification according to the International Society for the Study of Vascular Anomalies (ISSVA) is of major importance to guide proper treatment. Imaging plays a crucial role to classify vascular malformations according to their dominant vessel type, anatomical extension, and flow pattern. Several imaging concepts including color-coded Duplex ultrasound/contrast-enhanced ultrasound (CDUS/CEUS), 4D computed tomography angiography (CTA), magnetic resonance imaging (MRI) including dynamic contrast-enhanced MR-angiography (DCE-MRA), and conventional arterial and venous angiography are established in the current clinical routine. Besides the very heterogenous phenotypes of vascular malformations, molecular and genetic profiling has recently offered an advanced understanding of the pathogenesis and progression of these lesions. As distinct molecular subtypes may be suitable for targeted therapies, capturing certain patterns by means of molecular imaging could enhance non-invasive diagnostics of vascular malformations. This review provides an overview of subtype-specific imaging and established imaging modalities, as well as future perspectives of novel functional and molecular imaging approaches. We highlight recent pioneering imaging studies including thermography, positron emission tomography (PET), and multispectral optoacoustic tomography (MSOT), which have successfully targeted specific biomarkers of vascular malformations.

Risk and protective factors for post-thrombotic syndrome after deep venous thrombosis.

OBJECTIVE: The most frequent complication of deep venous thrombosis (DVT) is post-thrombotic syndrome (PTS). We recently showed inhibition of varicose vein development by atorvastatin and rosuvastatin. The aim of this study was to test the influence of lipid-lowering therapy with statins on PTS development. METHODS: All patients between January 2002 and June 2018 with diagnosed DVT were enrolled in this study and analyzed retrospectively. Documentation was performed using the standardized system M1 (CompuGroup Medical, Koblenz, Germany) throughout the observation period. Patients received therapeutic anticoagulation and compression stockings. In case of recurrent DVT, patients received lifelong therapeutic anticoagulation. All patients received clinical examination and duplex ultrasound evaluation 3 to 6 months after primary diagnosis and annually thereafter. RESULTS: A total of 579 patients with DVT were enrolled in this study. Of these patients, 414 (71%) developed PTS (337/414 [81%] presented with the mild version; mean Villalta score, 5.79). Risk factors for PTS development were recurrent DVT (P = .001) and malignant disease (P = .001). Protective factors were therapy with platelet aggregation inhibitors (P = .049) and lipid-lowering therapy with statins (P = .001). After multivariable analysis, the only risk factor was recurrent DVT (P = .001), and the only protective factor was lipid-lowering therapy (P = .001). CONCLUSIONS: Post-thrombotic changes might be reduced by lipid-lowering therapy.

Midterm outcome of renal function after branched thoracoabdominal aortic aneurysm repair.

OBJECTIVE: The aim of this study was to investigate the incidence and impact of acute and chronic kidney dysfunction after branched endovascular aortic aneurysm repair (BEVAR) perioperatively and during follow-up. METHODS: Patients with a thoracoabdominal aortic aneurysm were treated with BEVAR. Serum creatinine; estimated glomerular filtration rate at baseline, after 48 hours, at discharge, and after 1 and two years; perioperative results; and outcome during follow-up were evaluated. RESULTS: Treatment of thoracoabdominal aortic aneurysm using BEVAR was performed in 113 patients (mean age, 71 years; 79 male) with 434 side branches and two additional fenestrations (0.46%) for renovisceral perfusion. Sixty patients (53%) underwent staged procedures with temporary aneurysm sac perfusion and secondary side branch completion. Perioperative mortality was 9 of 113 (8%). Postoperative acute kidney injury (AKI) was observed in 41 of 113 patients (36%) with recovery of renal function after 2 years in most patients. However, chronic kidney disease (CKD) stage progression after 1 and 2 years was observed in 25 of 104 patients (24%) and 17 of 52 patients (32.7%), respectively. Seven patients (6.7%) required permanent dialysis during 2 years of follow-up. Risk factors for AKI were nonstaged procedures (P = .02) and multiorgan failure (P = .01). CKD progression was related to renal branch reinterventions (P = .047), all branch reinterventions (P = .03), and postoperative AKI (P = .001). During follow-up, survival was decreased in patients with AKI, especially in those with nonmalignant diseases (P = .01). CONCLUSIONS: Postoperative AKI after BEVAR was observed in about one-third of patients associated with increased CKD stages after 2 years. Preoperative CKD was not a risk factor for postoperative AKI or perioperative outcome. The prevention of AKI by staged procedures, early interventions for renal side branch complications, and regular surveillance is recommended to improve outcomes.

Treatment of popliteal vein aneurysms.

OBJECTIVE: Popliteal vein aneurysms are associated with high risk for deep venous thrombosis (DVT) and pulmonary embolism. The goal of this study was to report treatment strategies for popliteal vein aneurysms and their outcome after long-term follow-up. METHODS: All patients between June 1993 and June 2018 with diagnosed popliteal vein aneurysm were enrolled in this study and analyzed retrospectively. They received regular surveillance alone or treatment. Patients were offered aneurysm resection or lifelong anticoagulation if they had aneurysm size of twice normal vein diameter. All patients received clinical examination and duplex ultrasound examination 3 to 6 months after operation or primary diagnosis and annually thereafter. RESULTS: A total of 39 patients (aneurysm size, mean 23.3 mm) were treated by either operation or anticoagulation (31/39 [79%]) or surveillance alone (8/39 [21%]). Patients with an aneurysm >20 mm in diameter had a significantly higher incidence of turbulent flow on duplex ultrasound examination with higher risk for development of DVT (P = .029). Of the 31 patients with a therapeutic approach, 29 (94%) preferred resection, whereas 2 (6%) patients were treated with lifelong anticoagulation and compression. Mean follow-up was 57.9 ± 12.5 months. CONCLUSIONS: According to these results, it seems that patients with large popliteal vein aneurysms experience DVT more frequently. Therefore, popliteal vein aneurysms >20 mm should be considered for surgical treatment or lifelong anticoagulation, depending on the patient's preference.

Complex treatment of vascular prostheses infections.

Infections after vascular reconstructions are very rare; however, when they occur, they are associated with a high risk of morbidity. In order to obtain the best results possible, the treatment needs to be initiated as early as possible, from the very first signs of infection, and it needs to be carried out in centers specializing in vascular surgery. The aim of the present study was to assess the incidence of infections in a single university center.This retrospective analysis over a 2-year period is based on the medical reports of hospitalized patients who were diagnosed with infection following revascularization.From 2013 to 2014, a number of 151 open reconstructive surgical procedures were performed. 15 patients suffered from infection (10%) of the vascular reconstruction. Of these patients, 40% have had an aorto-bifemoral bypass, 53%-a femoro-popliteal bypass, and 7% (n = 1)-an axillo-femoral bypass. According to the Samson classification, the patients were categorized as follows: group 2: 6 cases, group 3: 2 cases, group 4: 4 cases, and group 5: 3 cases. The most frequent bacteria found were methicillin-resistant Staphylococcus aureus (MRSA) (n = 6, 40%), followed by S aureus (n = 5, 33%). The treatment options were: application of antibiotics alone without any invasive treatment in 3 patients, local irrigation and debridement in 6 patients, complete explantation of the prosthesis with a new extra-anatomic bypass in 6 cases, and partial excision of the prosthesis, which was replaced and covered with muscle flap, in 3 cases. The amputation rate in our study was 18%, which corresponds to the rates published in the literature.The treatment of infections in vascular surgery needs to be complex and adapted to each individual patient, because infections being in a permanent dynamic state. The treatment needs to be performed in specialized centers that have large experience in vascular surgery, in order for the patient to have the best chances of survival and protection from amputation.

Evaluation of visible spinal arteries on computed tomography angiography before and after branched stent graft repair for thoracoabdominal aortic aneurysm.

OBJECTIVE: The aim of this study was to evaluate the impact of intercostal and lumbar segmental arteries (SAs) detectable on computed tomography angiography (CTA) on the risk of spinal cord ischemia (SCI) in patients undergoing single-step or two-staged branched endovascular aneurysm repair (BEVAR). METHODS: A retrospective analysis of patients treated with branched stent grafts for thoracoabdominal aortic aneurysm at a single institution from January 2009 to June 2015 was performed. Data including preoperative comorbidities, perioperative and aneurysm-related parameters, presence and type of endoleak, and rate of severe SCI at discharge or 30 days after the procedure were collected. Preoperative and postoperative contrast-enhanced CTA images were semiquantitatively analyzed by two independent investigators, and the number of visible SAs in the stented aorta before and after BEVAR was evaluated to find a possible correlation with severe SCI. RESULTS: Seventy-seven patients were treated for thoracoabdominal aortic aneurysm with BEVAR (47 men; mean age, 71.0 years), 40 (51.9%) of them with temporary aneurysm sac perfusion (TASP; open branch/TASP group) and 37 without (single-step group). The groups were comparable regarding parameters related to the patient, aneurysm type, and endovascular procedure. Severe SCI or paraplegia was observed in 10 patients (12.3%), and SCI was lower in the open branch/TASP group (2/40) compared with the single-step group (8/37; P = .032). The number of visible SAs in the intentionally overstented aortic segment was significantly reduced on postoperative CTA (10.0 vs 15.57 SAs; P < .001) in comparison to preoperative CTA imaging, with similar results in the open branch/TASP group (9.48 vs 15.83 SAs) and the single-step group (10.57 vs 15.30 SAs; P < .001 for both groups). Within the open branch/TASP group, more visible SAs were detected during the TASP interval in comparison to postoperative CTA after side branch completion (12.93 vs 9.48 SAs; P < .001). Receiver operating characteristic curve analysis in the single-step group revealed a cutoff point of 15 SAs on preoperative CTA with correlation to severe SCI (P = .006). In the high-risk subgroup of patients with 15 or more overstented SAs during BEVAR, staged open branch/TASP procedures again reduced the risk of SCI in comparison to the single-step patients (1/20 vs 8/22; P = .008). CONCLUSIONS: More spinal arteries are visible during the TASP interval, supporting the open branch and TASP concept with a reduction of severe SCI during BEVAR. An intentional coverage of more than 15 SAs is related to an increased risk of SCI, and the rate of paraplegia was reduced after staged BEVAR with open branch/TASP in these high-risk patients.

MAGE qPCR improves the sensitivity and accuracy of EBUS-TBNA for the detection of lymphatic cancer spread.

INTRODUCTION: Microscopic examination of histologic slides or cytologic specimens of mediastinal lymph node samples obtained by diagnostic mediastinoscopy or endobronchial ultrasound-guided fine-needle aspiration (EBUS-TBNA) is routinely used for the staging of lung cancer patients. Therefore, we explored whether the detection of tumor-associated mRNA in lymph node samples from patients with suspected lung cancer adds diagnostic accuracy to conventional histopathological staging. METHODS: We examined 202 lymph nodes obtained by EBUS-TBNA or mediastinoscopy from 89 patients with lung cancer. Lymph node samples from patients with nonmalignant disease were available as controls (60 samples from 31 patients). Real-time quantitative mRNA analysis was performed for melanoma antigen-A genes (MAGE-A 1-6, MAGE-A 12) using a LightCycler 480 instrument. RESULTS: MAGE transcript levels in control and cancer patients differed widely, and the 95% confidence interval served to define the threshold between negative and positive samples. MAGE 1 to 6 transcripts were detected in 35 of 122 (28.7%) lymph nodes obtained by EBUS-TBNA and 16 of 80 (20.0%) lymph nodes obtained by mediastinoscopy. MAGE 12 transcripts were detected in 10 of 122 (8.2%) lymph nodes obtained by EBUS-TBNA and 9 of 80 (11.3%) lymph nodes obtained by mediastinoscopy. Although the accuracy of histopathological diagnosis after EBUS-TBNA and mediastinoscopy was 69.6% and 84.1%, respectively, it increased to 81.2% and 86.4%, respectively, when combined with MAGE-quantitative polymerase chain reaction. CONCLUSIONS: The combination of EBUS-TBNA and MAGE-quantitative polymerase chain reaction increases the accuracy of tumor cell detection to the level seen with mediastinoscopy.

Expression of melanoma-antigen-A (MAGE-A) in disseminated tumor cells in regional lymph nodes of patients with operable non-small cell lung cancer.

PURPOSE: Single disseminated tumor cells are detectable in regional lymph nodes of 30-50% patients with early-stage non-small cell lung cancer (NSCLC). This study investigated if these disseminated tumor cells express MAGE-A and thus might be targeted by adjuvant anti-MAGE-A immunotherapies. EXPERIMENTAL DESIGN: Lymph nodes of 32 consecutive patients without neoadjuvant therapy were removed by systematic lymphadenectomy during resection of NSCLC. One-hundred of these lymph nodes were cut into two equal halves which were examined using either routine histo-pathology or quantitative reverse transcriptase PCR (qRT-PCR). qRT-PCR amplification of cytokeratin 19 transcripts was applied for the detection of disseminated tumor cells. Expression of MAGE-A was analyzed using one single primer pair amplifying subgroups MAGE-A1 to -A6 in one qRT-PCR reaction. RESULTS: Ninety-four (94%) lymph nodes were tumor-free by histo-pathology. qRT-PCR detected disseminated tumor cells in 26 (28%) of these lymph nodes resulting in 19 (59%) patients with disseminated tumor cells. All of the remaining 6 lymph nodes that were judged by the pathologist to contain tumor cells exhibited CK19 transcripts. Fifteen (46%) lymph nodes with disseminated tumor cells contained MAGE-A transcripts resulting in 12 (37%) patients with disseminated tumor cells which expressed MAGE-A. There was no correlation between clinico-pathological parameters and the occurrence of disseminated tumor cells or their MAGE-A expression. CONCLUSIONS: Since 37% of patients with operable NSCLC harbored disseminated tumor cells that expressed MAGE-A, only these patients might benefit from adjuvant immunotherapies directed against MAGE-A1 to -A6. This study may provide a basis for the preselection of patients to be included in such immunotherapy trials after resection of NSCLC.

Sublobar resections in stage IA non-small cell lung cancer: segmentectomies result in significantly better cancer-related survival than wedge resections.

OBJECTIVE: Sublobar resections spare pulmonary function and offer a method of increasing resection rates in patients with lung cancer and limited functional operability. Previous studies demonstrated an increased local recurrence rate following wedge resections compared to segmentectomies in stage IA non-small cell lung cancer (NSCLC). However, a prognostic impact of this observation has never been shown and is still under debate. Therefore, this study has been performed to analyse the cancer-related survival of sublobar resections in stage IA patients. METHODS: Over a 17-year period 87 patients underwent sublobar complete resection (R0) of stage IA NSCLC via thoracotomy. Sublobar resection was reserved for patients with cardiopulmonary impairment. Wedge resections with selective lymphadenectomy were performed in 31 patients (36%) and segmentectomies with systematic lymphadenectomy in 56 patients (64%). Patient characteristics, functional parameters, tumour specifics and follow-up duration were analysed concerning their distribution between the two groups. Kaplan-Meier curves were compared and possible joint effects between prognostic parameters were analysed by multivariate Cox regression analysis. RESULTS: The median follow-up duration was 45 months. There was no significant difference between the two groups in gender (p=0.11), age (p=0.08), American Society of Anesthesiology physical performance status (ASA)-score (p=0.32), forced expiratory volume in 1s FEV(1) (p=0.08), tumour size (p=0.30), histology (p=0.17), grading (p=0.12), complication rate (p=0.15) and follow-up duration (p=0.29). The mean number of dissected lymph nodes in segmentectomies (12+/-6) was higher than in wedge resections (6+/-3) (p=0.0001). The 5-year survival rate was 63%. There were significantly less locoregional recurrences (p=0.001), an equal distribution of distant metastases (p=0.53) and a better cancer-related survival (p=0.016) following segmentectomies compared to wedge resections. Cox regression analysis showed that the prognostic effect of the resection type was independent from gender, age, ASA-score, respiratory function, tumour size, tumour histology, grading and number of dissected lymph nodes (p=0.04, relative risk 1.16). CONCLUSIONS: Studies investigating survival after sublobar resection of stage IA NSCLC should always distinguish between anatomical segmentectomies and wedge resections. If limited functional operability requires a sublobar resection of stage IA NSCLC, segmentectomy with systematic lymphadenectomy should be preferred.