Minimally Invasive Video-Assisted Parathyroidectomy: Lesson Learned from 137 cases

Abstract: Background: Since February 1997, a technique of minimally invasive video-assisted parathyroidectomy (MIVAP) was developed at our institution for the treatment of sporadic primary hyperparathyroidism (sPHPT). In this study we analyzed the entire series of patients who underwent MIVAP during the last 3 years. Study Design: One hundred thirty-seven patients with sPHPT were selected for MIVAP. Selection criteria were: diagnosis of single adenoma based on preoperative localization studies (ultrasonography, sestamibi scintigraphy, or both), and no previous neck surgery or concomitant large multinodular goiter. The procedure, already described, is performed by a gasless video-assisted technique through a single 1.5-cm central skin incision above the sternal notch. Quick, intraoperative parathyroid hormone assay was used in 134 cases (97.8%) to confirm the complete removal of all hyperfunctioning parathyroid tissue. Results: Mean operative time was 54.3 +/- 22.6 minutes. The conversion rate was 8.8%. One laryngeal nerve palsy was registered (0.7%), as was one case of persistent hyperparathyroidism. In six patients (4.4%) a transient symptomatic postoperative hypocalcemia was observed. Two thyroid lobectomies were associated using the same minimally invasive access. At a mean followup of 15.4 +/- 10.6 months, all but two patients were normocalcemic. The cosmetic result was considered excellent by most of the patients (92.8%). Conclusions: Although not all patients with sPHPT are eligible for MIVAP, this approach can now be proposed in a bigger proportion (67% of patients). As already demonstrated in a previous study, also in a large series of patients, after greater experience has been achieved, the results and the operative time are the same as in traditional surgery, with better cosmetic result and a less painful course. (J Am Coll Surg 2000; 191:613-618. (C) 2000 by the American College of Surgeons)

Acquired Carotid-Jugular Fistula: Its Changing History and Management

Abstract Purpose. To highlight the changes that have come about in recent years in the etiology, diagnosis, and treatment of acquired carotid-jugular fistulas. Methods. We present a review of the literature on acquired carotid-jugular fistulas (CJFs), which includes studies from World Wars I and II up to today and a retrospective analysis of the lesion reports published in the period 2000–2012, with an update of Talwar's table. The case study of one patient suffering from an untreated, long-standing CJF recently treated by us is also presented and included in the updated table. Results. Thanks to early treatment of acute lesions by reconstructive and endovascular surgery, incidence of posttraumatic carotid-jugular fistulas is decreasing, while the number of iatrogenic ones due to medical advances is concomitantly increasing, specifically because of the ever more widespread use of central venous catheters for venous pressure monitoring, parenteral nutrition, and hemodialysis. Conclusion. Although such lesions seem destined to diminish in the future thanks to the above-mentioned diagnostic and therapeutic advances, the increasing number of internal jugular vein catheterizations performed worldwide implies that physicians will still be dealing with carotid-jugular fistulas for many years to come

Antineoplastic Effects of PPARγ Agonists, with a Special Focus on Thyroid Cancer

Peroxisome Proliferator-Activated Receptor-γ (PPARγ) is a ligand-activated nuclear hormone receptor that functions as transcription factor and plays an important role in lipid metabolism and insulin sensitization. Recent studies have shown that PPARγ is overexpressed in many tumor types, including cancers of breast, lung, pancreas, colon, glioblastoma, prostate and thyroid differentiated/anaplastic cancers. These data suggest a role of PPARγ in tumor development and/or progression. PPARγ is emerging as a growth-limiting and differentiation-promoting factor, and it exerts a tumor suppressor role. Moreover, naturally-occurring and synthetic PPARγ agonists promote growth inhibition and apoptosis. Thiazolidinediones (TZDs) are synthetic agonists of PPARγ that were developed to treat type II diabetes. These compounds also display anticancer effects which appear mainly to be independent of their PPARγ agonist activity. Various preclinical and clinical studies strongly suggest a role for TZDs both alone and in combination with existing chemotherapeutic agents, for the treatment of cancer. Differentiation therapy involves the use of agents with the ability to induce differentiation in cells that have lost this ability, i.e. cancer cells, targeting pathways capable of re-activating blocked terminal differentiation programs. PPARγ agonists have been shown to induce differentiation in solid tumors such as thyroid differentiated/ anaplastic cancers and sarcomas. However, emerging data suggest that chronic use of TZDs is associated with increased risk of adverse cardiovascular events. The exploration of newer PPARγ agonists can help in unveiling the underlying mechanisms of these drugs, providing new molecules that are able to treat cancer, without increasing the cardiovascular risk of neoplastic patients

Day case parathyroidectomy: is this the right way for the patients?

Minimally-invasive video-assisted parathyroidectomy (MIVAP) can be considered as the primary treatment of choice for single parathyroid adenoma. Often, this technique is performed in a day surgery setting and is associated with regional anaesthesia (RA). Many studies have already reported the feasibility and safety of MIVAP in day surgery. Here our focus has been on the patient's personal experience with these procedures through an assessment of their recovery at home

Cabozantinib in Thyroid Cancer

Cabozantinib is an oral once-daily multitarget tyrosine kinase inhibitor of MET, VEGFR2, RET, acting against KIT, AXL, FLT3 and Tie-2. Cabozantinib has shown anti-cancer effects in preclinical and clinical models of cancers derived from both epithelial and mesenchymal origins [prostate cancer, non small lung cancer, medullary thyroid cancer (MTC) and differentiated thyroid cancer (DTC), renal cell carcinoma, etc.]. In a Phase III clinical study, cabozantinib improved PFS (11.2 months versus 4.0 months in the placebo group) of patients with MTC (independently of age, bone metastases, RET status and prior treatment). Cabozantinib was approved in 2012 by FDA for metastatic MTC and in 2013 by EMA. Cabozantinib has been also evaluated in metastatic DTC patients, because they have activation on tyrosine kinases, including MET, VEGFR2 and RET, suggesting the possible use of cabozantinib in metastatic DTC. Actually, two Phase II trials of cabozantinib in DTC patients resistant to RAI are ongoing. To increase the antineoplastic effect of cabozantinib, and to overcome the occurrence of drug resistance, combination studies with other anticancer agents are ongoing. In conclusion, cabozantinib has shown to exert an important therapeutic effect in patients with MTC improving PFS. In DTC patients, cabozantinib has shown promising results

Sorafenib and Thyroid Cancer

Sorafenib (Nexavar) is a multikinase inhibitor, which has demonstrated both anti-proliferative and anti-angiogenic properties in vitro and in vivo, inhibiting the activity of targets present in the tumor cell [c-RAF (proto-oncogene serine/threonine-protein kinase), BRAF, V600EBRAF, c-KIT, and FMS-like tyrosine kinase 3] and in tumor vessels (c-RAF, vascular endothelial growth factor receptor-2, vascular endothelial growth factor receptor-3, and platelet-derived growth factor receptor β). For several years, sorafenib has been approved for the treatment of hepatocellular carcinoma and advanced renal cell carcinoma. After previous studies showing that sorafenib was able to inhibit oncogenic RET mutants, V600EBRAF, and angiogenesis and growth of orthotopic anaplastic thyroid cancer xenografts in nude mice, some clinical trials demonstrated the effectiveness of sorafenib in advanced thyroid cancer. Currently, the evaluation of the clinical safety and efficacy of sorafenib for the treatment of advanced thyroid cancer is ongoing. This article reviews the anti-neoplastic effect of sorafenib in thyroid cancer. Several completed (or ongoing) studies have evaluated the long-term efficacy and tolerability of sorafenib in patients with papillary and medullary aggressive thyroid cancer. The results suggest that sorafenib is a promising therapeutic option in patients with advanced thyroid cancer that is not responsive to traditional therapeutic strategies

The safety and efficacy of vandetanib in the treatment of progressive medullary thyroid cancer

Introduction: Traditional therapies for advanced or metastatic progressive medullary thyroid cancer (pMTC) are poor effective. Several TKIs have been tested in clinical trials in pMTC patients. Areas covered: This paper reviews efficacy and safety of vandetanib in the treatment of pMTC. Expertcommentary: Vandetanib (trade name CAPRELSA® [Vandetanib]) has been shown to improve progression-free survival (30.5 vs 19.3 months in controls) in pMTC patients. Vandetanib is approved by FDA and EMA for metastatic MTC in adults; in adolescents and children with metastatic or locally advanced MTC, vandetanib seems to be effective. The most common adverse events in vandetanib-treated patients are: diarrhea, rash, folliculitis, nausea, QTc prolongation, hypertension and fatigue. In patients with aggressive differentiated thyroid cancer, vandetanib has shown promising results. Further research is needed to determine the ideal targeted therapy, based on tumor molecular characterization and host factors, to obtain the best response in terms of survival and quality of life

Oral L-thyroxine liquid versus tablet in patients submitted to total thyroidectomy for thyroid cancer (without malabsorption): A prospective study

Objective: No consistent data are present in literature about the effectiveness of Levothyroxine (L-T4) liquid formulation in patients without malabsorption after thyroidectomy. The aim of this study is to compare the effectiveness of L-T4 liquid formulation, with L-T4 tablets, in thyroid cancer patients after thyroidectomy (without malabsorption or drug interference). Methods: One hundred five patients were recruited; 52 patients were treated with liquid L-T4 formulation, while 53 with L-T4 tablets, at the same dosage (1.5 mcg/kg/day). Patients started to assume the drug the day after surgery, 30 min before breakfast. In both groups circulating levels of thyrotropic hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) were dosed at week 6 (first control), and then at week 12 (second control). Results: We obtained significantly lower TSH values in the liquid L-T4 group patients, compared to the tablet L-T4 group, at the first control (P < .05), and at the second control (P < .01), while FT4 and FT3 levels were not significantly different. Hypothyroid range (TSH > 3.6 mcU/mL) was significantly more prevalent in the patients treated with L-T4 tablet. Conclusions: A better control of TSH was observed in thyroidectomized patients (without malabsorption, gastric disorders, or drug interference) with liquid L-T4 regimen. Level of Evidence: 2c-Outcomes Research

Advancements in the treatment of hypothyroidism with L-T4 liquid formulation or soft gel capsule: an update

INTRODUCTION: The most recent advance concerning levothyroxine (L-T4) therapy is the development of novel oral formulations: the liquid preparation, and the soft gel capsule. AREAS COVERED: This review evaluates the most recent clinical studies about these new formulations. The liquid formulation has been shown to overcome: the food and beverages intereference with L-T4 tablets absorption, caused by food or coffee at breakfast; malabsorption induced by the increased gastric pH, resulting from atrophic gastritis, or due to proton-pump inhibitors; and malabsorption after bariatric surgery. The use of liquid L-T4 has been studied also in pregnancy, newborns and infants, suggesting a better bioequivalence than tablets. Finally, liquid L-T4 is more active than tablets in the control of thyroid-stimulating hormone (TSH) in hypothyroid patients without malabsorption, drug interference, or gastric disorders, leading to a hypothesized higher absorption of liquid L-T4 also in these patients. Few studies have evaluated soft gel L-T4 with promising results in patients with malabsorption related to coffee or gastritis. EXPERT OPINION: Liquid L-T4 (and soft gel capsules) are more active than the tablet L-T4 in the control of TSH in hypothyroid patients with gastric disorders, malabsorption, or drug interference, but also in patients without absorption disorders

Selective use of vandetanib in the treatment of thyroid cancer

Vandetanib is a once-daily orally available tyrosine kinase inhibitor that works by blocking RET (REarranged during Transfection), vascular endothelial growth factor receptor (VEGFR-2, VEGFR-3), and epidermal growth factor receptor and to a lesser extent VEGFR-1, which are important targets in thyroid cancer (TC). It is emerging as a potentially effective option in the treatment of advanced medullary thyroid cancer (MTC) and in dedifferentiated papillary thyroid cancer not responsive to radioiodine. The most important effect of vandetanib in aggressive MTC is a prolongation of progression-free survival and a stabilization of the disease. Significant side effects have been observed with the vandetanib therapy (as fatigue, hypertension, QTc prolongation, cutaneous rash, hand-and-foot syndrome, diarrhea, etc), and severe side effects can require the suspension of the drug. Several studies are currently under way to evaluate the long-term efficacy and tolerability of vandetanib in MTC and in dedifferentiated papillary TC. The efficacy of vandetanib in patients with MTC in long-term treatments could be overcome by the resistance to the drug. However, the effectiveness of the treatment could be ameliorated by the molecular characterization of the tumor and by the possibility to test the sensitivity of primary TC cells from each subject to different tyrosine kinase inhibitor. Association studies are evaluating the effect of the association of vandetanib with other antineoplastic agents (such as irinotecan, bortezomib, etc). Further research is needed to determine the ideal therapy to obtain the best response in terms of survival and quality of life