Cervical Lymph Node Dissection for Papillary Thyroid Cancers: A Decade Experience of a Single Surgical Team.

Background: All patients undergoing thyroid operations should be subjected to preoperative neck ultrasound (US) followed by fine needle aspiration cytology (FNAC) of suspicious lesions. In Western countries, thyroid surgeons routinely perform neck ultrasound. The role of prophylactic central neck dissection (PCND) remains a topic of debate. For treatment of papillary thyroid carcinoma (PTC), in 2014 we introduced two new adjuncts: PCND based on criteria of the European Society of Endocrine Surgeons (ESES) consensus group and surgeon-performed US (S-US). Methods: In order to better understand the role of these two adjuncts in our shift of strategy we aimed to evaluate the outcomes of our patients in two successive 5-year time periods based on a retrospective analysis of our prospectively maintained database (total of 286 patients were included in this study). Results: The two groups were similar regarding epidemiological and clinical data. FNAC was done in only 21.66% of all PTC cases. PTC diagnosis was done in the majority of suspicious cases by FS. S-US guided the selective lateral node dissections (LND), leading to more lymph node metastases detections and it also surpassed endocrinologist performed US (E-US) in terms of PPV. PCND rate of complications was significantly higher due only to transient hypoparathyroidism. Conclusions: Preoperative surgeon-performed ultrasonography is a useful tool in the arsenal of PTC treatment. The systematic preoperative FNAC diagnosis and intraoperative frozen sections in uncertain cases are mandatory. PCND is a safe method of treatment and staging in PTC.

Near infrared light examination as part of the management of sporadic pancreatic head insulinoma: Case report.

INTRODUCTION: We report the case of a 77-year-old female patient with the diagnosis of pancreatic head insulinoma, in whom we used near infrared light (NIR) to detect synchronous pancreatic tumors and potential secondary lymph node or liver involvement. The patient presented with hypoglycemia manifesting by lipothymia. With the diagnosis of secretory neuroendocrine tumor (insulinoma) of the pancreatic head, cephalic pancreatoduodenectomy with the preservation of the pylorus was performed after NIR visualization of the pancreatic tumor mass. At 6, 12, 18 months postoperatively, the patient no longer had hypoglycemia and her general state was good. CONCLUSION: NIR with indocyanine green (ICG) evidences pancreatic neuroendocrine tumors, as well as possible synchronous tumors and secondary lymph node or liver involvement.

Treatment with Sildenafil and Donepezil Improves Angiogenesis in Experimentally Induced Critical Limb Ischemia.

Objectives. In this study, we aimed to demonstrate the role of sildenafil (an antagonist of phosphodiesterase type 5 (PDE-5)) and donepezil (a specific and reversible inhibitor of acetylcholinesterase (Ach)) in increasing ischemia-induced angiogenesis. Method. Critical limb ischemia was induced by ligation of the common femoral artery followed by ligation of the common iliac artery. The operated animals were divided into 3 groups: receiving sildenafil, receiving donepezil, and surgery alone; the contralateral lower limb was used as a negative control. The results were controlled based on clinical score and Doppler ultrasound. Gastrocnemius muscle samples were taken from all animals, both from the ischemic and nonischemic limb and were used for histopathological and immunohistochemical examination for the evaluation of the number of nuclei/field, endothelial cells (CD31), dividing cells (Ki-67), and vascular endothelial growth factor (VEGFR-3). Results. An increasing tendency of the number of nuclei/field with time was observed both in the case of sildenafil and donepezil treatment. The formation of new capillaries (the angiogenesis process) was more strongly influenced by donepezil treatment compared to sildenafil or no treatment. This treatment significantly influenced the capillary/fiber ratio, which was increased compared to untreated ligated animals. Sildenafil treatment led to a gradual increase in the number of dividing cells, which was significantly compared to the negative control group and compared to the ligation control group. The same effect (increase in the number of Ki-67 positive cells) was more obvious in the case of donepezil treatment. Conclusion. Donepezil treatment has a better effect in ligation-induced ischemia compared to sildenafil, promoting angiogenesis in the first place, and also arteriogenesis.

Influence of risk factors and comorbidities on the successful therapy and survival of patients with critical limb ischemia.

BACKGROUND: Critical limb ischemia (CLI) is associated with an increased risk of limb amputation, low quality of life and cardiovascular death. The aim of this study is to identify the prognostic factors of mortality, revascularization failure and amputation failure, as part of risk factors for athero-sclerosis and comorbidities. PATIENTS AND METHODS: We examined 198 patients operated for CLI. Cox analysis was performed to discern the factors that were associated with failure of initial surgical therapy and death. RESULTS: For survival analysis, a significant model emerged with hypertension (p=0.00), cardiac comorbidities (p=0.00), renal comorbidities (p=0.04) and respiratory comorbidities (p=0.02) as significant predictors. Regarding the time to amputation failure, there was a significant model with insulin treated diabetes (p=0.00), coronary artery disease (p=0.02) and cerebrovascular disease (p=0.05) as significant predictors. CONCLUSIONS: Significant predictors for mortality in CLI patients are high risk hypertension, severe coronary artery disease, renal failure requiring dialysis and chronic obstructive pulmonary disease. The association of these prognostic factors results in a proportional decrease of survival. The predictors for amputation failure were, in addition to local factors, insulin treated diabetes, coronary artery disease and cerebrovascular disease. The revascularization for limb salvage depends on the correct indication and accurate surgical technique.

Influence of sildenafil and donepezil administration on the serum redox balance in experimentally induced lower limb critical ischemia.

INTRODUCTION: Chronic lower limb ischemia (CLLI) leads to endothelial cell dysfunctions and endothelial lesions. The use of substances that release nitric oxide and activate endothelial nitric oxide synthase has proved to be useful in increasing angiogenesis and arteriogenesis under critical ischemia conditions. OBJECTIVES: To investigate the therapeutic effect of Sildenafil and Donepezil with a vasodilating action in experimentally induced CLLI and on serum redox homeostasis. MATERIAL AND METHOD: The research was performed in 3 groups of rats (n=10 animals/group) with experimentally induced CLLI: group I - control group; group II - animals treated postoperatively with a therapeutic dose of sildenafil, and group III - animals treated postoperatively with a therapeutic dose of donepezil. Oxidative stress (OS) indicators (malondialdehyde - MDA, protein carbonyls - PC), antioxidant (AO) defense indicators (reduced glutathione - GSH and oxidized glutathione - GSSH), and ceruloplasmin (CP) were determined on days 7, 14, 21 and 30. Statistical processing was performed using the Excel application (Microsoft Office 2007), with the StatsDirect v.2.7.2 software. RESULTS: Changes in OS were evidenced in all groups on account of a decrease in MDA and PC. The greatest OS decrease in all groups was on day 30. AO defence changes were represented by decreased levels of GSH and GSSG in all groups, at the studied moments. Intracellular AO defense in the cytosol, nucleus and mitochondria was similar in all groups, (decreased GSH, GSSG and GSH/GSSG ratio). We found increased extracellular levels of GSH, GSSG, and CP and increased extracellular GSH/GSSG ratio at level compared to values on day 7. CONCLUSIONS: 1) The administration of sildenafil (group II) and donepezil (group III) has favorable effects on reducing OS in experimentally induced CLLI. 2) Sildenafil and Donepezil administration stimulates extracellular AO defense on account of CP. 3) Sildenafil and Donepezil administration influences intracellular redox homeostasis on account of the GSH/GSSG couple, the major redox buffer in the body.

Defective DSB repair correlates with abnormal nuclear morphology and is improved with FTI treatment in Hutchinson-Gilford progeria syndrome fibroblasts.

Impaired DSB repair has been implicated as a molecular mechanism contributing to the accelerating aging phenotype in Hutchinson-Gilford progeria syndrome (HGPS), but neither the extent nor the cause of the repair deficiency has been fully elucidated. Here we perform a quantitative analysis of the steady-state number of DSBs and the repair kinetics of ionizing radiation (IR)-induced DSBs in HGPS cells. We report an elevated steady-state number of DSBs and impaired repair of IR-induced DSBs, both of which correlated strongly with abnormal nuclear morphology. We recreated the HGPS cellular phenotype in human coronary artery endothelial cells for the first time by lentiviral transduction of GFP-progerin, which also resulted in impaired repair of IR-induced DSBs, and which correlated with abnormal nuclear morphology. Farnesyl transferase inhibitor (FTI) treatment improved the repair of IR-induced DSBs, but only in HGPS cells whose nuclear morphology was also normalized. Interestingly, FTI treatment did not result in a statistically significant reduction in the higher steady-state number of DSBs. We also report a delay in localization of phospho-NBS1 and MRE11, MRN complex repair factors necessary for homologous recombination (HR) repair, to DSBs in HGPS cells. Our results demonstrate a correlation between nuclear structural abnormalities and the DSB repair defect, suggesting a mechanistic link that may involve delayed repair factor localization to DNA damage. Further, our results show that similar to other HGPS phenotypes, FTI treatment has a beneficial effect on DSB repair.

Lamin A/C expression is a marker of mouse and human embryonic stem cell differentiation.

Nuclear lamins comprise the nuclear lamina, a scaffold-like structure that lines the inner nuclear membrane. B-type lamins are present in almost all cell types, but A-type lamins are expressed predominantly in differentiated cells, suggesting a role in maintenance of the differentiated state. Previous studies have shown that lamin A/C is not expressed during mouse development before day 9, nor in undifferentiated mouse embryonic carcinoma cells. To further investigate the role of lamins in cell phenotype maintenance and differentiation, we examined lamin expression in undifferentiated mouse and human embryonic stem (ES) cells. Wide-field and confocal immunofluorescence microscopy and semiquantitative reverse transcription-polymerase chain reaction analysis revealed that undifferentiated mouse and human ES cells express lamins B1 and B2 but not lamin A/C. Mouse ES cells display high levels of lamins B1 and B2 localized both at the nuclear periphery and throughout the nucleoplasm, but in human ES cells, B1 and B2 expression is dimmer and localized primarily at the nuclear periphery. Lamin A/C expression is activated during human ES cell differentiation before downregulation of the pluripotency marker Oct-3/4 but not before the downregulation of the pluripotency markers Tra-1-60, Tra-1-81, and SSEA-4. Our results identify the absence of A-type lamin expression as a novel marker for undifferentiated ES cells and further support a role for nuclear lamins in cell maintenance and differentiation.

Omental free-tissue transfer: indications and results from personal experience.

Between 1987-2002, omental free-tissue transfer was used in 11 patients, aged 6-65 years (mean age, 37.6). The omentum was used for the treatment of brachial plexus injury pain (3 cases), Romberg's disease (1 case), defects of the extremities occurring with chronic obstructive arterial disease (2 cases), posttraumatic lesions (3 cases), and following oncological resections (2 cases). In 2 cases, omental tissue represented the secondary option, after the failure of muscular tissue transfer. In 2 patients, the omental tissue transfer helped to preserve the knee. There was 1 failure, followed by amputation of the thigh. Two patients died from their underlying disease 10 and 36 months, respectively, after the operation.