Nicola Avenia

Complications of Thyroid Surgery: Analysis of a Multicentric Study on 14,934 Patients Operated on in Italy over 5 Years

Complication rates associated with thyroid surgery can be evaluated only through analysis of case studies and follow-up data. This study covers postoperative data from 14,934 patients subjected to a follow-up of 5 years. Among them, 3130 (20.9%) underwent total lobectomy (TL), 9599 (64.3%) total thyroidectomy (TT), 1448 (9.7%) subtotal thyroidectomy with a monolateral remnant (MRST), and 757 (5.1%) subtotal thyroidectomy with bilateral remnants (BRST). A total of 6% of the patients had already been operated on. Persistent hypoparathyroidism occurred after 1.7% of all the operations, and temporary hypoparathyroidism was noted in 8.3%. Permanent palsy of the laryngeal recurrent nerve (LRN) occurred in 1.0% of patients, transient palsy in 2.0%, and diplegia in 0.4%. The superior laryngeal nerve was damaged in 3.7%; dysphagia occurred in 1.4% of cases, hemorrhage in 1.2%, and wound infection in 0.3%. No deaths were reported. A significant rate of LRN damage was noted, which has an important impact on the patient’s social life. Hypoparathyroidism after total thyroidectomy is an important complication that can be successfully treated by therapy, although it is not always easily managed in special circumstances such as in young persons or pregnant women. The complications associated with thyroid surgery must be kept in mind so the surgeon can carefully evaluate the surgical and medical therapeutic options, have more precise surgical indications, and be able to give the patient adequate information.

Robotic resection compared with laparoscopic rectal resection for cancer: systematic review and meta‐analysis of short‐term outcome

Aim  The study aimed to compare robotic rectal resection with laparoscopic rectal resection for cancer. Robotic surgery has been used successfully in many branches of surgery but there is little evidence in the literature on its use in rectal cancer.

Laparoscopic vs open resection for rectal cancer: a meta‐analysis of randomized clinical trials

Aim  Laparoscopic and open rectal resection for cancer were compared by analysing a total of 26 end points which included intraoperative and postoperative recovery, short‐term morbidity and mortality, late morbidity and long‐term oncological outcomes.

Genotyping of an Italian papillary thyroid carcinoma cohort revealed high prevalence of BRAF mutations, absence of RAS mutations and allowed the detection of a new mutation of BRAF oncoprotein (BRAFV599Ins)

Objectives  The genes RET and RAS, and more recently BRAF, have been shown to be frequently mutated in human papillary thyroid carcinomas (PTC). The aim of this study was to genotype for these mutations a cohort of thyroid tumours collected at our institutions.

Clinical implications of BRAF mutation in thyroid carcinoma

Significant progress has recently been made in the clinical management of papillary thyroid carcinoma. The accuracy of diagnosis and prognostic stratification of this type of carcinoma are high but still fall below 100%. Lack of effective treatments for advanced stage papillary thyroid carcinoma leads to death in some patients. Approximately half of all such carcinomas harbor mutations in the gene encoding the serine/threonine-kinase B-type Raf kinase (BRAF), resulting in constitutive activation of the mitogen-activated protein kinase-extracellular-signal-regulated kinases signal transduction pathway. There is intriguing evidence that BRAF mutation testing of papillary thyroid carcinoma might improve the diagnosis, prognostic stratification and treatment of these tumors but large, prospective trials are needed to define the actual clinical impact of these approaches.

Recurrent Laryngeal Nerve Damage and Phonetic Modifications after Total Thyroidectomy: Surgical Malpractice Only or Predictable Sequence?

Modifications of phonation occurring after total thyroidectomy (TT) are usually attributed to surgical malpractice, but other causes of voice impairment even in nonoperated subjects should also be taken into account. This study analyzes 208 patients who underwent TT from January 1, 1999 through December 31, 2001. Follow-up ended on December 31, 2003. Only cases in which the surgeon ruled out the possibility of operative damage to the laryngeal nerves were included. All patients underwent pre- and postoperative clinical and instrumental nose and throat examination (NTE). Preoperatively, 86 patients (41%) showed hoarseness or dysphagia: 4 (2%) monoplegia and 12 (6%) hypomobility of the vocal cords due to impaired function of the recurrent laryngeal nerve (RLN); 6 (3%) cord hypotonia due to impairment of the superior laryngeal nerve (SLN); 34 (16%) dysphagia: and 30 (14%) hoarseness due to other causes. At follow-up 1 month after surgery, 71 patients (34%) had an onset of previously absent signs and symptoms: 8 (4%) had palsy of one vocal cord (2% permanent); 6 (3%) had cord hypomobility (all temporary); 12 (6%) had cord hypotonia due to disease of the SLN, 4 of which (2%) were permanent; 44 patients (21%) had symptoms due to scarring and adhesions between the laryngotracheal axis and the prethyroid muscles and between these and the skin. One patient (0.5%) had a nodular cord lesion that occurred after 3 months. Overall, more than one-third of the patients had preoperative voice modifications or swallowing impairment, around one-third had these problems after TT, and less than one-third were free of pre- and postoperative complications. The surgeon’s care to avoid damage to the anatomica integrity of the of laryngeal nerves does not exclude functional problems of the nerves and of laryngeal dynamics. In fact, such problems could be referred to outcomes linked to the operation itself (hematoma, edema, scarring adhesion) or to events that only temporarily follow surgery but must be considered as an unavoidable sequel (e.g., neuritis, viral neuritis, myopathy). The patient should undergo a careful clinical and instrumental NTE to detect conditions prior to surgery, and the information provided by the surgeons should be thorough to allow the patient to be aware of all possible sequels and consequences.

Large-artery stiffness: A reversible marker of cardiovascular risk in primary hyperparathyroidism

OBJECTIVE Patients with primary hyperparathyroidism (pHPT) are at increased risk of cardiovascular mortality. We investigated whether aortic stiffness, an early marker of arteriosclerosis and a strong predictor of cardiovascular risk, is increased in pHPT, and whether it improves after parathyroidectomy. METHODS Twenty-four patients with mild pHPT (age 56 ± 10 years, blood pressure 136/85 mmHg, serum calcium 2.55-3.00 mmol/L) and 48 control subjects individually matched with cases by age, sex and blood pressure underwent aortic (carotid-femoral) and upper-limb (carotid-radial) pulse wave velocity (PWV) determination by applanation tonometry in a case-control study. Subjects with renal disease, diabetes, treated hypertension or overt cardiovascular disease were excluded from the study. Seventeen of the patients with pHPT were re-examined 4 weeks after surgical parathyroidectomy. RESULTS Aortic PWV was significantly higher among pHTP patients (11.4 ± 2 vs 9.6 ± 2 m/s, p<0.001). In a conditional logistic regression analysis, pHPT was independently associated with an increased risk of having an aortic PWV >12 m/s (odds ratio 3.28, 95% confidence interval 1.21-8.93). As expected, surgery was accompanied by a reduction in serum calcium (from 2.77 ± 0.2 to 2.25 ± 0.1 mmol/L, p<0.001) and parathyroid hormone (from 29.6 ± 10 to 3.3 ± 2 pmol/L, p<0.001). Aortic PWV decreased after surgery (from 10.9 ± 2 to 9.8 ± 2 m/s, p=0.003). The change in aortic PWV remained significant also after adjustment for changes in blood pressure (p<0.01). Changes in upper-limb PWV generally paralleled those in aortic PWV. CONCLUSION pHPT is associated with increased aortic stiffness, which improves after parathyroidectomy. Our data demonstrate that aortic stiffness may improve upon removal of hyperparathyroid stimuli.

Biochemical and molecular characterization of the novel BRAF V599Ins mutation detected in a classic papillary thyroid carcinoma

Activating mutations of the BRAF gene are the most common genetic alterations in papillary thyroid carcinomas (PTCs) and the T1799A transversion, resulting in BRAFV600E, appeared virtually unique in this cancer type. Here, we report on the identification in a classic PTC of a novel BRAF mutation, namely a 1795GTT insertion, resulting in BRAFV599Ins, and describe its biochemical and molecular characterization. Kinase assays carried out on BRAFV599Ins and BRAFV600E revealed a three- to five-fold increase in the enzymatic activity of both mutants with respect to BRAFWT. Similarly, evaluation of BRAF-induced phosphorylation of MEK, MAPK and RSK revealed a significant MAPK cascade activation in cells expressing BRAFV599Ins or BRAFV600E, but not in cells expressing BRAFWT. Molecular dynamic simulations showed a destabilization of the inactive conformation of the enzyme in both BRAFV599Ins and BRAFV600E mutants, but not in BRAFWT. The analysis of the interaction energies inside the catalytic site allowed to demonstrate the presence of repulsive electrostatic forces acting on the activation loop and moving from inward to outward of the mutant enzymes. Finally, focus assays in NIH-3T3 cells confirmed a high transformation rate in the cells transfected either with BRAFV599Ins or BRAFV600E. In conclusion, this study demonstrated that BRAFV599Ins, as BRAFV600E, is a ‘gain of function’ mutation, characterized by a constitutive catalytic activation, which accounts for its causative role in the studied PTC.

A randomized controlled trial to evaluate the efficacy of ultrasound-guided laser photocoagulation for treatment of benign thyroid nodules

This randomized controlled study was designed to test the efficacy and safety of percutaneous ultrasound (US)-guided laser photocoagulation (PLP) for treatment of subjects with compressive symptoms due to benign thyroid nodules and/or at high surgical risk. Twenty six subjects were randomized to the intervention (no. 13, age 68±3 yr, mean±SEM) or observation (no. 13, age 71±2 yr) groups. In the control group, the volume of nodules did not significantly change over the 30 week period of observation. In the intervention group, median nodule volume at baseline was 8.2 ml (range 2.8–26.9) and was not significantly different from that of the control group. Nodules decreased significantly (p<0.0001) by 22% after 2 weeks (6.5ml; range 2.4–16.7) and by 44% after 30 weeks (4.6 ml; range 0.69–14.2). Energy given was correlated (p<0.05) with the reduction of thyroid nodule volume. All patients tolerated the treatment well and reported relief from compressive and cosmetic complaints (p<0.05). At the time of enrolment 7/13 (54%) and 6/13 (46%) of patients in the intervention and control groups, respectively, had sub clinical hyperthyroidism. PLP normalized thyroid function at 6 and 30 weeks after treatment. In conclusion, PLP is a promising safe and effective procedure for treatment of benign thyroid nodules in patients at high surgical risk.

Impact of prophylactic central compartment neck dissection on locoregional recurrence of differentiated thyroid cancer in clinically node-negative patients: A retrospective study of a large clinical series

BACKGROUND In clinically node-negative patients with differentiated thyroid cancer (DTC), indications for routine central lymph node dissection (RCLD) are the subject of intensive research, and surgeons are divided between the pros and cons of this surgery. To better define the role of neck dissection in the treatment of DTC, we analyzed retrospectively the results in three centers in Italy. METHODS The clinical records of 752 clinically node-negative patients with DTC who underwent operative treatment between January 1998 and December 2005 in three endocrine surgery referral units were evaluated retrospectively. The complications and medium- and long-term outcomes of total thyroidectomy (TT) alone (performed in 390 patients: group A) and TT combined with bilateral RCLD (362 patients: group B) were analyzed and compared. RESULTS The incidence of permanent hypoparathyroidism and permanent unilateral vocal folds was 1% and 0.8% in group A and 3.6% and 1.7% in the group B, respectively. Bilateral temporary recurrent nerve palsy was observed in one of the 362 patients in group B. After a follow-up of 9.5 ± 3.5 years (mean ± SD), the locoregional recurrence rate with positive cervical lymph nodes was not substantially significantly different between the two groups. CONCLUSION In our series, TT combined with bilateral RCLD was associated with a greater rate of transient and permanent complications. Similar incidences of locoregional recurrence were reported in the two groups of patients. Considering the recent trend toward routine central lymphadenectomy, further studies are needed to evaluate the benefits of these different approaches.