Use of loupes magnification and microsurgical technique in thyroid surgery: ten years experience in a single center.

AIM: The use of microsurgical technique and loupes magnification as a support to traditional surgery can help surgical performance and prevent complications in thyroid surgery. PATIENTS AND METHODS: Between January 2004 and December 2014, 782 patients with thyroid diseases were operated by our team with microsurgical technique and loupes magnification 4.5x. All patients had pre and postoperative vocal cords assessment and calcemia and the collected data were analysed. RESULTS: Among the 782 patients, only six patients (0.77%) had unilateral vocal fold immobility treated with medical therapy, phoniatric and neck physiotherapy. All six patients showed complete laryngeal recovery of motility 6/8 weeks after treatment. There were not cases of permanent monolateral or bilateral vocal cord palsy. In 84 patients there were signs and symptoms of hypocalcemia. In 81 patients (10.36%) the restoring of biochemical parameters and the resolution of symptoms occurred between 2 and 6 weeks and in 3 cases (0.38%) there was permanent hypocalcemia more than six months. CONCLUSION: The use of microsurgical technique and loupes magnification in thyroid surgery are safety and effective procedures, that require an appropriate training in reconstructive microsurgery, but may significantly reduce post-operative complications. Here, we report for the first time the largest series of thyroid surgery performed with the use of microsurgical technique and loupes magnification, analysing the postoperative morbidity. In view of our results, we suggest the routine use of 4.5X loupes and microsurgical technique in thyroid surgery.

Long-term (12 to 18 months) functional voice assessment to detect voice alterations after thyroidectomy.

OBJECTIVES: Even when thyroidectomy preserves vocal cord motility it may leave patients with changes in voice quality. Although superior laryngeal nerve (LSN) damage after thyroidectomy manifests with aspecific symptoms, laryngoscopy discloses only slight morphological changes that are difficult to assess. We want to investigate the voice function in asymptomatic patients one year after thyroidectomy and to compare the obtained data against those of a healthy control group. PATIENTS AND METHODS: Thirty adult patients who had undergone thyroidectomy, all of them euphonic before and after the operation, were submitted to a complete voice assessment including voice self-evaluation tools, videolaryngostroboscopy and spectrographic analysis of voice. Primary outcome measures were differences between surgical patients and control group in terms of microperturbation of voice intensity and amplitude as measured by spectrographic analysis. RESULTS: In patients who had undergone thyroidectomy, acoustic parameters indicating amplitude microperturbations resulted slightly altered. All these values exceeded normal MDVP thresholds. Another interesting finding in our study sample concerns the lower F0 values we recorded in women patients after surgery than in healthy controls. Voice alterations may reflect prelaryngeal muscle scarring or fibrosis. Consider the possible alterations of vocal quality caused by scarring after surgery therefore strongly recommend surgery when the situation allows it, not to dissect the prelaryngeal muscles but only to spread apart. CONCLUSIONS: Our study conducted at least one year after thyroid surgery underlines that surgery-related slight voice deficits can persist over time. More refined phoniatric testing discloses voice alterations that normalize without specific rehabilitation therapy, therefore confirming that certain acoustic changes are clinically unimportant.

Secondary prevention of latex allergy in children: analysis of results.

OBJECTIVE: Latex allergy has become an increasing and clinically important problem. Several recommendation for secondary preventive measures have been advised. The aims of the study were to illustrate the results of the latex-safe protocol and to evaluate in allergic patients the role of risk factors for the development of latex allergy. METHODS: Latex-safe treatment was divided into the following phases: anamnestic identification, allergologic assessment, patient selection, intervention programme, preventive medication, operating room equipment, postoperative management, patient and family training, follow-up. RESULTS: Between 1998 and 2004, 6.832 patients underwent 7.333 operations. Anamnestic and diagnostic tests showed that 26 patients had latex allergy. 44 secondary perioperative latex-safe management have been accomplished in 26 children. No allergic event or complications linked to the procedure occurred. Atopy, congenital malformations frequently associated with latex allergy and the presence of 5 or more surgical procedures were the major risk factors recognized. Six out of the 26 patients (23%) had only one risk factor (atopy). Twenty out of 26 children (77%) had several associated risk factors: 8 of them had simultaneously 9 of the 10 analysed risk factors. Our data shows that, the higher their number, the higher the gravity of the allergy. CONCLUSIONS: Although latex allergy is a limited phenomenon, it is nevertheless quite frequent within risk groups. Most patients have simultaneously many risk factors for the development of such an allergy, and the occurrence of several risk factors increases severity of the allergy. Latex-safe perioperative management offers guarantees of safety against latex allergy phenomena.

Membrane-bound protein kinase A inhibits smooth muscle cell proliferation in vitro and in vivo by amplifying cAMP-protein kinase A signals.

cAMP-dependent protein kinase is anchored to discrete cellular compartments by a family of proteins, the A-kinase anchor proteins (AKAPs). We have investigated in vivo and in vitro the biological effects of the expression of a prototypic member of the family, AKAP75, on smooth muscle cells. In vitro expression of AKAP75 in smooth muscle cells stimulated cAMP-induced transcription, increased the levels of the cyclin-dependent kinase-2 inhibitor p27(kip1), and reduced cell proliferation. In vivo expression of exogenous AKAP75 in common carotid arteries, subjected to balloon injury, significantly increased the levels of p27(kip1) and inhibited neointimal hyperplasia. Both the effects in smooth muscle cells in vitro and in carotid arteries in vivo were specifically dependent on the amplification of cAMP-dependent protein kinase (PKA) signals by membrane-bound PKA, as indicated by selective loss of the AKAP75 biological effects in mutants defective in the PKA anchor domain or by suppression of AKAP effects by the PKA-specific protein kinase inhibitor. These data indicate that AKAP proteins selectively amplify cAMP-PKA signaling in vitro and in vivo and suggest a possible target for the inhibition of the neointimal hyperplasia after vascular injury.

8-chloro-cAMP inhibits smooth muscle cell proliferation in vitro and neointima formation induced by balloon injury in vivo.

OBJECTIVES: The aims of the present study were to assess 1) the effect of 8-C1-cAMP (cyclic-3'-5'-adenosine monophosphate) on vascular smooth muscle cell (VSMC) proliferation in vitro and 2) the efficacy of systemic administration of 8-C1-cAMP on neointimal formation after balloon injury in vivo. BACKGROUND: Neointimal formation after vascular injury is responsible for restenosis after arterial stenting. Recently, 8-C1-cAMP, a cAMP analogue that induces growth arrest, has been safely administered in phase I studies in humans. METHODS: The effect of 8-C1-cAMP on cell proliferation was first assessed on SMCs in vitro. To study the effects of cAMP in vivo, balloon injury was performed in 67 rats using a 2F Fogarty balloon catheter. RESULTS: The 8-C1-cAMP markedly inhibited VSMC proliferation in vitro, reduced protein kinase A (PKA) RIalpha subunit expression, and induced PKA RIIbeta subunit expression. In addition, 8-C1-cAMP reduced, in a dose-dependent manner, neointimal area and neointima/media ratio after balloon injury. The proliferative activity, assessed by proliferating nuclear cell antigen immunostaining, revealed a reduction of proliferative activity of VSMCs in vivo in the 8-C1-cAMP group. Moreover, the systemic administration of 8-C1-cAMP did not affect renal function, blood pressure and heart rate. CONCLUSIONS: We conclude that 8-C1-cAMP potently inhibits VSMC proliferation in vitro and reduces neointima formation by balloon injury in vivo after systemic administration. These data may have a clinical relevance in designing future strategies to prevent restenosis after arterial stenting and perhaps after percutaneous transluminal coronary angioplasty.

Activation of cAMP-PKA signaling in vivo inhibits smooth muscle cell proliferation induced by vascular injury.

Injury of the arterial wall induces the formation of the neointima. This structure is generated by the growth of mitogenically activated smooth muscle cells of the arterial wall. The molecular mechanism underlying the formation of the neointima involves deregulated cell growth, primarily triggered by the injury of the arterial wall. The activated gene products transmitting the injury-induced mitogenic stimuli have been identified and inhibited by several means: transdominant negative expression vectors, antisense oligodeoxynucleotides, adenovirus-mediated gene transfer, antibodies and inactivating drugs. Results of our study show that local administration of 3',5'-cyclic AMP and phosphodiesterase-inhibitor drugs (aminophylline and amrinone) to rats markedly inhibits neointima formation after balloon injury in vivo and in smooth muscle cells in vitro. The growth inhibitory effect of aminophylline was completely reversed by the inhibition of cAMP-dependent protein kinase A (PKA). These findings indicate an alternative approach to the treatment of diseases associated with injury-induced cell growth of the arterial wall, as stimulation of cAMP signaling is pharmacologically feasible in the clinical setting.

Smooth muscle cell proliferation is proportional to the degree of balloon injury in a rat model of angioplasty.

BACKGROUND: A variable degree of smooth muscle cell (SMC) proliferation after balloon injury has been reported in previous rat studies. It is unknown whether balloon injury induces c-fos expression and whether it is related to the degree of vascular injury in vivo. Therefore, we tested the hypothesis that proportional increases in neointimal formation and c-fos expression might be present after different degrees of balloon dilation. METHODS AND RESULTS: Angioplasty of the carotid artery was performed with a balloon catheter. Vascular injury was evaluated at 0, 0.5, 1.0, 1.5, and 2 atm (n = 6 for all). In 40 additional rats, total RNA dot blots were performed to assess the effect of various degrees of balloon injury on c-fos expression. SMC proliferation proportional to the increases of inflation pressure was found between 0 and 2 atm with neointimal areas of 0.002 +/- 0.002, 0.069 +/- 0.014, 0.128 +/- 0.043, 0.190 +/- 0.010, and 0.255 +/- 0.041 mm2, respectively. When the degree of SMC proliferation (neointima and neointima/media ratio) was plotted against balloon inflation pressure, a linear relation was observed (r = .733, P < .001 and r = .755, P < .001, respectively). An increase in c-fos expression proportional to the degree of injury was found 30 minutes after injury. CONCLUSIONS: Neointimal proliferation produced by balloon injury is related to balloon inflation pressure, supporting the concept of an SMC proliferative response proportional to the degree of injury. The increase in SMC proliferation is associated with a proportional increase in the early expression of the c-fos nuclear proto-oncogene.

Inhibition of cellular ras prevents smooth muscle cell proliferation after vascular injury in vivo.

Proliferation of smooth muscle cells of the arterial wall in response to local injury is an important aetiologic factor of vascular proliferative disorders such as atherosclerosis and restenosis after angioplasty. Ras proteins are key transducers of mitogenic signals from membrane to nucleus in many cell types. We investigated the role of ras proteins in the vascular response to arterial injury by inactivating cellular ras of rats in which the common carotid artery was subjected to balloon injury. DNA vectors expressing ras transdominant negative mutants, which interfere with ras function, reduced neointimal formation after injury. Our results indicate a key role for ras in smooth muscle cell proliferation and show that the local delivery of transdominant negative mutants of ras in vivo might prevent some of the acute vascular injury caused by balloon injury.

[Gene therapy for the treatment of restenosis after coronary angioplasty]. / Terapia genica per il trattamento della ristenosi dopo angioplastica coronarica.

Accumulation and proliferation of vascular smooth muscle cells are associated with atherosclerosis and hypertension. Proliferation of smooth muscle cells constitutes a major pathological event responsible for long-term failure of coronary and peripheral arterial bypass graft as well as the development of restenosis after percutaneous transluminal coronary angioplasty (PTCA). The incidence of restenosis after PTCA has been reported to be as high as 40-45% within 3-6 months. Major advantages in recombinant deoxyribonucleic acid (DNA) technology and eukaryotic gene regulation allow to hypothesize gene therapy as a potential treatment for inherited and acquired diseases. Gene therapy is the introduction of genes into somatic cells to correct an inherited or acquired disorder through the synthesis of missing or defective protein. Although no disease has yet been treated by gene therapy, several gene transfer protocols have recently been undertaken. We have studied the expression of foreign DNA that has been introduced into smooth muscle cells after balloon carotid injury in a rat model of angioplasty. The effects of different degree of balloon injury on neointima formation and c-fos expression was also assessed. Our data demonstrate that site-specific gene expression can be achieved by direct gene transfer in vivo and could be applied to the treatment of restenosis after PTCA.

[Diagnostic reliability of ultrasonography in the preoperative staging of the N parameter in head and neck neoplasms]. / Attendibilità diagnostica dell'ecotomografia nella stadiazione preoperatoria del parametro N nelle neoplasie del capo-collo.

The demonstration of metastatic involvement of neck nodes is a crucial step in the staging of patients with head and neck tumors. Diagnostic accuracy, sensitivity, and specificity of US in the detection of lymph node metastases were evaluated in 48 patients with this type of malignancy. The patients subsequently underwent surgical node dissection. Comparison of US, clinical and histological data demonstrated US to have 93.7% diagnostic accuracy, 100% sensitivity, and 84% specificity--the corresponding clinical values being 81%, 79%, and 84%, respectively. Among several US parameters, a substantial role in differentiating metastatic from tumor-free lymph nodes was played by the evaluation of roundness index (RI), and by the demonstration of an intranodal hyperechoic stria: RI value was always higher than 2 in tumor-free nodes and the hyperechoic stria was always absent in metastatic nodes. US approach never failed to demonstrate metastatic nodes while clinics missed them in 6 patients. Thus, US appears the most valuable diagnostic tool for staging head and neck tumors; its diagnostic accuracy can be increased by the combination with US-guided aspiration biopsy.