ABSTRACT
Critical leg ischemia (CLI) complicated by diabetes mellitus (DM), which is a very common and dangerous disease, represents the ultimate stage of peripheral arterial disease. Patients are treated with antiplatelet drugs, statins and limb revascularization, but a significant number of patients are not candidate for revascularization. Literature shows that in such cases, gene therapy could be a perfect therapeutic option. The aim of our study was to evaluate efficacy of double vascular endothelial growth factor/hepatocyte growth factor (VEGF/HGF) gene therapy in patients with CLI complicated by DM. We observed that 90 days after administration, serum level of VEGF and ankle-brachial index increased significantly (p < 0.001) and rest pain decreased significantly compared with the control group (p < 0.002). Moreover considerable improvement in vascularization was observed in computed tomography angiography (P = 0.04). Based on the results of this study, we suggest that the therapy with pIRES/VEGF165/HGF bicistronic plasmid administration is a safe and effective method of treatment of patients with both CLI and DM. Graphical abstract.
Subject(s)
Diabetes Mellitus, Type 2/therapy , Genetic Therapy , Hepatocyte Growth Factor/genetics , Ischemia/therapy , Neovascularization, Physiologic , Peripheral Arterial Disease/therapy , Vascular Endothelial Growth Factor A/genetics , Aged , Aged, 80 and over , Biomarkers/blood , Blood Glucose/metabolism , Critical Illness , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/physiopathology , Female , Functional Status , Humans , Internal Ribosome Entry Sites/genetics , Ischemia/blood , Ischemia/genetics , Ischemia/physiopathology , Male , Middle Aged , Peripheral Arterial Disease/blood , Peripheral Arterial Disease/genetics , Peripheral Arterial Disease/physiopathology , Plasmids/genetics , Poland , Recovery of Function , Time Factors , Treatment Outcome , Vascular Endothelial Growth Factor A/bloodABSTRACT
BACKGROUND: Prognosis of peripheral artery disease (PAD), especially critical limb ischemia (CLI), is very poor despite the development of endovascular therapy and bypass surgery. Many patients result in having leg amputation. We decided to investigate the safety and efficacy of plasmid of internal ribosome entry site/vascular endothelial growth factor (VEGF) 165/hepatocyte growth factor (HGF) gene therapy (GT) in patients suffered from CLI. METHODS: Administration of plasmid of internal ribosome entry site/VEGF165/HGF was performed in 12 limbs of 12 patients with rest pain and ischemic ulcers due to CLI. Plasmid was injected into the muscles of the ischemic limbs. The levels of VEGF in serum and the ankle-brachial index (ABI) were measured before and after treatment. RESULTS: Mean (±SD) plasma levels of VEGF increased nonsignificantly from 258 ± 81 pg/L to 489 ± 96 pg/L (P > 0.05) 2 weeks after therapy, and the ABI improved significantly from 0.27 ± 0.20 to 0.50 ± 0.22 (P < 0.001) 3 months after therapy. Ischemic ulcers healed in 9 limbs. Amputation was performed in 3 patients because of advanced necrosis and wound infection. However, the level of amputations was lowered below knee in these cases. Complications were limited to transient leg edema in 3 patients and fever in 2 patients. CONCLUSIONS: Intramuscular administration of plasmid of internal ribosome entry site/VEGF165/HGF is safe, feasible, and effective for patients with critical leg ischemia.
Subject(s)
Genetic Therapy , Hepatocyte Growth Factor/genetics , Ischemia/therapy , Leg Ulcer/therapy , Lower Extremity/blood supply , Peripheral Arterial Disease/therapy , Vascular Endothelial Growth Factor A/genetics , Adult , Aged , Amputation, Surgical , Ankle Brachial Index , Critical Illness , Female , Genetic Therapy/adverse effects , Hepatocyte Growth Factor/blood , Humans , Internal Ribosome Entry Sites , Ischemia/diagnosis , Ischemia/genetics , Ischemia/physiopathology , Leg Ulcer/diagnosis , Leg Ulcer/genetics , Leg Ulcer/physiopathology , Male , Middle Aged , Peripheral Arterial Disease/diagnosis , Peripheral Arterial Disease/genetics , Peripheral Arterial Disease/physiopathology , Prospective Studies , Risk Factors , Time Factors , Treatment Outcome , Vascular Endothelial Growth Factor A/blood , Wound HealingABSTRACT
BACKGROUND: Squamous cell carcinoma of the esophagus is one of the neoplasms characterized by an exceptionally latent course, dynamic development and poor prognosis. The stage of the disease at the time of treatment is started the greatest impact on the long term results. OBJECTIVES: The aim of this study was to evaluate selected clinical-pathological features as prognostic factors for long term survival among patients who have undergone esophagectomies due to squamous cell carcinoma. The features analyzed were age, gender, the stage of the disease and the type of tumor. Long-term survival rates (2, 5 and 10 years) were analyzed in relation to the particular features. MATERIAL AND METHODS: The study group consisted of 65 patients diagnosed with squamous cell carcinoma of the thoracic esophagus who underwent esophagectomies between 1997 and 2008. The statistical analysis was performed with Statistca 8.0 software. Gehan-Wilcoxon, chi and Kaplan-Meier tests were carried out. RESULTS: The research did not find any statistically significant correlation between the patients' gender and survival time (Gehan-Wilcoxon p = 0.83; log-rank p = 0.86). The results showed no statistically significant correlation between the patients' age and survival time (Gehan-Wilcoxon p = 0.75; log-rank p = 0.47). The only statistically significant impact of the stage of the disease on the survival time was a correlation between the longer survival time and the stage I and II of the disease (Chi p = 0.15). The log-rank test revealed that survival time is significantly shorter in cases of involved nodes (Gehan-Wilcoxon p = 0.054; log-rank p = 0.014). CONCLUSIONS: Among the clinical-pathological features investigated, only metastases in regional lymph nodes had any significant impact on long-term survival.