Lazaros Reppas

Gene-based therapies in patients with critical limb ischemia

ABSTRACT Introduction: Critical limb ischemia (CLI) constitutes a life-limiting and life-threatening disease. Revascularization, either endovascular or surgical, remains the best treatment option accompanied by medication and risk factor modification. Patients unable to undergo revascularization, referred as ‘no-option patients’, have been the center of interest the last few years, subjected to treatment therapies based on proteins (mainly growth factors) involved in angiogenesis via gene delivery to the ischemic tissue. Areas covered: This review focuses on these growth factors, gives an update of the studies available, discusses the possible problems that influence outcomes and describes future perspectives including possible new technologies that will improve them. Additionally, the authors attempt to place therapeutic angiogenesis to the bigger frame of tailored therapy in CLI. Expert opinion: Although encouraging in the beginning, growth factor therapy results have been equivocal and inconclusive. And while it would be misleading to approach gene therapy as panacea, its effect on the micro-circulatory level activating angiogenesis and arteriogenesis could act as an important adjunct in personalized treatment.

Multi-center feasibility study of microwave radiometry thermometry for non-invasive differential diagnosis of arterial disease in diabetic patients with suspected critical limb ischemia

AIMS Diagnosis of vascular involvement in diabetic foot ulceration (DFU) remains challenging. We conducted a proof of concept study to investigate the feasibility of microwave radiometry (MWR) thermometry for non-invasive differential diagnosis of critical limb ischemia (CLI) in subjects with DFU. METHODS This prospective, multi-center, study included 80 participants, divided into four groups (group N: normal control subjects; group DN: participants with diabetes and verified neuropathic ulcers without vascular involvement; group DC: participants with diabetes and CLI and group NDC: participants with CLI without diabetes). Vascular disease was confirmed with angiography. All patients underwent MWR (RTM-01-RES:University of Bolton, UK) to record mean tissue temperatures at various pre-determined foot sites. Comparisons of temperature measurements between study groups were performed using one-way ANOVA and Dunn tests. ROC analysis was performed to determine sensitivity, specificity and cut-off value of MWR for CLI diagnosis. RESULTS Temperatures recorded in vicinity to the foot ulcers of participants with diabetes and CLI were similar to those with CLI without diabetes, but significantly lower than in subjects with neuropathic ulcers without vascular involvement and normal controls (group DC:29.30°C±1.89 vs. group NDC:29.18°C±1.78vs. group N:33.01°C±0.45 vs. group DN:33.39°C±1.37;P<.0001). According to ROC analysis, cut-off temperature value to diagnose CLI was <31.8°C (area under the curve: 0.984; 95% CI: 0.965-1.005;P<.001), with a sensitivity of 100.0% (95%CI: 90.26-100.0) and specificity of 88.37% (95% CI: 74.92-96.11). CONCLUSIONS Tissue temperatures in vicinity to ulcers were significantly lower in participants with CLI, with or without diabetes, compared to non-ischemic controls. MWR could be used for differential diagnosis of arterial ischemia in subjects with DFU.

Current Evidence and future perspectives on Anti-Platelet and Statin Pharmacotherapy for Patients with Symptomatic Peripheral Arterial Disease.

BACKGROUND Pharmacotherapy is of increasing interest in peripheral arterial disease (PAD), with novel therapies aiming at different factors contributing to the disease. For antiplatelet therapy, there is no unanimous agreement regarding the nature or duration of optimal antiplatelet therapy so as to reduce major adverse cardiovascular and limb-related events (e.g. repeat interventions and amputations). However, evidence on novel more potent antithrombotic agents, drug combinations and personalized antiplatelet therapy for PAD patients is accumulating. Similarly, statins are now considered as a standard of care in PAD patients, due to their multiple actions which include plaque stabilization, antiinflammatory properties and regression of atheroma. CONCLUSION This review focuses on current evidence available for various antiplatelet regimens and statin therapy for PAD and discusses future perspectives. We consider randomized controlled trials, together with the most important reviews and meta-analyses. Treatment algorithms based on currently available data.

Computed tomography-guided percutaneous microwave ablation of hepatocellular carcinoma in challenging locations: safety and efficacy of high-power microwave platforms

Abstract Objective: To evaluate the clinical efficacy/safety of CT-guided percutaneous microwave ablation for HCC in challenging locations using high-power microwave platforms. Materials and methods: A retrospective review was conducted in 26 patients with 36 HCC tumours in challenging locations (hepatic dome, subcapsular, close to the heart/diaphragm/hepatic hilum, exophytic) undergoing CT-guided percutaneous microwave ablation in a single centre since January 2011. Two different microwave platforms were used both operating at 2.45 GHz: AMICA and Acculis MWA System. Patient demographics including age, sex, tumour size and location, as well as technical details were recorded. Technical success, treatment response, patients survival and complication rate were evaluated. Results: Treated tumours were located in the hepatic dome (n = 14), subcapsularly (n = 16), in proximity to the heart (n = 2) or liver hilum (n = 2), while two were exophytic tumours at segment VI (n = 2). Mean tumour diameter was 3.30 cm (range 1.4–5 cm). In 3/26 patients (diameter >4 cm), an additional session of DEB-TACE was performed due to tumour size. Technical success rate was 100%; complete response rate was recorded in 33/36 tumours (91.6%). According to Kaplan–Meier analysis, survival rate was 92.3% and 72.11% at 24- and 60-month follow-up, respectively. There were no major complications; two cases of minor pneumothorax and two cases of small subcapsular haematoma were resolved only with observation requiring no further treatment. Conclusion: CT-guided percutaneous microwave ablation for hepatocellular carcinoma tumours in challenging locations and up to 5 cm in diameter can be performed with high efficacy and safety rates.

Clinical Benefit of Pazopanib in a Patient with Metastatic Chondrosarcoma: A Case Report and Review of the Literature

Chondrosarcoma is a rare malignancy characterized by the production of cartilage matrix, displaying heterogeneous histopathology and clinical behavior. Due to lack of effective treatment for advanced disease, the clinical management of metastatic chondrosarcoma is exceptionally challenging. Chondrosarcomas harbor molecular abnormalities, such as overexpression of platelet-derived growth factor receptor (PDGFR)-alpha and PDGFR-beta, which are required for cancer development, progression, and metastasis. Pazopanib is a potent and selective multitargeted tyrosine kinase inhibitor, which co-inhibits stem cell growth factor receptor (c-KIT), fibroblast growth factor receptor (FGFR), PDGFR, and vascular endothelial growth factor receptor (VEGFR) and has demonstrated clinical activity in patients with advanced previously treated soft tissue sarcoma. Herein, we describe the unique case of a patient with metastatic chondrosarcoma who derived clinical benefit from pazopanib after first-line chemotherapy failure.

Massive hemoptysis in a patient with pulmonary embolism, a real therapeutic conundrum

Massive Hemoptysis and pulmonary embolism are two very severe and potentially fatal pulmonary emergencies requiring completely different treatments. We present the case of a 45-year old male transmitted to our Hospital for massive hemoptysis who at the same time was found to suffer from pulmonary embolism. Hemoptysis was treated with bronchial artery embolization which resulted in cessation of haemorrhage and allowed the administration of anticoagulant therapy a few days later. This case report gives an answer on how to manage a real therapeutic conundrum which is the coexistence of a massive hemoptysis and a concomitant pulmonary embolism.

High Extra-Tumoral 99mTc-Macroaggregated Albumin Accumulation in a Fatty Liver in a Candidate for Transarterial Radioembolization Treatment

A patient with non-alcoholic fatty liver disease (NAFLD) and unresectable small-sized (≤3cm) diffuse liver metastases from adenocarcinoma of the rectosigmoid junction was assessed for treatment with transarterial radioembolization (SIRT). The right hepatic arteriogram demonstrated several hypervascular lesions. However, the planar and the SPECT images of the subsequent right hepatic arterial 99mTc-MAA perfusion scintigraphy, revealed significantly heterogeneous distribution of 99mTc-MAA particles and “hot spots”, not corresponding to lesion-specific sites. The no coincidence of the angiographic and the scintigraphic findings could be possibly influenced by hemodynamic changes, due to the presence of significant NAFLD. Because of the high risk-benefit ratio, the patient was considered to be an inappropriate candidate for SIRT.