Diagnostic, therapeutic and health-care management protocol in thyroid surgery: a position statement of the Italian Association of Endocrine Surgery Units (U.E.C. CLUB).

PURPOSE: The diagnostic, therapeutic and health-care management protocol (Protocollo Gestionale Diagnostico-Terapeutico-Assistenziale, PDTA) by the Association of the Italian Endocrine Surgery Units (U.E.C. CLUB) aims to help treat the patient in a topical, rational way that can be shared by health-care professionals. METHODS: This fourth consensus conference involved: a selected group of experts in the preliminary phase; all members, via e-mail, in the elaboration phase; all the participants of the XI National Congress of the U.E.C. CLUB held in Naples in the final phase. The following were examined: diagnostic pathway and clinical evaluation; mode of admission and waiting time; therapeutic pathway (patient preparation for surgery, surgical treatment, postoperative management, management of major complications); hospital discharge and patient information; outpatient care and follow-up. RESULTS: A clear and concise style was adopted to illustrate the reasons and scientific rationales behind behaviors and to provide health-care professionals with a guide as complete as possible on who, when, how and why to act. The protocol is meant to help the surgeon to treat the patient in a topical, rational way that can be shared by health-care professionals, but without influencing in any way the physician-patient relationship, which is based on trust and clinical judgment in each individual case. CONCLUSIONS: The PDTA in thyroid surgery approved by the fourth consensus conference (June 2015) is the official PDTA of U.E.C. CLUB.

Ethical and medico-legal issues of TOETVA procedure and simulation on cadavers: a scoping review.

Conventional open thyroidectomy is still considered the gold standard for thyroid surgery. Transoral endoscopic thyroidectomy vestibular approach (also known as TOETVA) is often considered to be more advantageous than the other approaches, such as minimally invasive video assisted thyroidectomy, thyroidectomy via breast/axillary/retroauricular access, bilateral axillo-breast approach and axillo-bilateral breast approach. In this scoping review, we discuss the risks and the benefits of this surgical approach and its medico-legal and ethical implications, particularly focusing on the importance of practice on cadavers. Currently, there is little scientific evidence supporting TOETVA, since there are few papers on the comparison with the traditional open thyroidectomy that have been published and thus little data on the long-term outcomes of TOETVA are available. Since the better cosmetic outcome currently represents the main indication for this surgical technique, substantial medico-legal and ethical issues arise. Moreover, practice on cadavers can help surgeons to develop the technical and non-technical skills required to perform efficiently and safely this new surgical procedure.

Modulating the extension of thyroidectomy in patients with papillary thyroid carcinoma pre-operatively eligible for lobectomy: reliability of ipsilateral central neck dissection.

PURPOSE: Pre-operative work-up and macroscopic intraoperative inspection could overlook occult central neck nodal metastases in patients with papillary thyroid carcinoma (PTC). An occult N1a status is able to change the initial risk stratification in small, clinically unifocal PTC potentially scheduled for thyroid lobectomy (TL) making total thyroidectomy (TT) the preferable option. We aimed to verified the reliability of an intraoperative management protocol based on frozen section examination (FSE) of ipsilateral central neck nodes (IpsiCND) to identify, among patients scheduled for TL, those who could benefit of a more extensive surgical resection (TT plus bilateral central neck dissection -CND-). METHODS: Thirty PTC patients preoperatively classified as T1N0 underwent TL plus IpsiCND-FSE (TL-group). In case of positive FSE, TT plus bilateral CND was accomplished during the same surgical procedure. A comparative analysis was performed between TL-group and a control group (C-group), who underwent TT plus IpsiCND-FSE, matched by a propensity score analysis. RESULTS: Nodal metastases (>2 mm) were found at final histology in 5/30 patients in the TL-group and in 6/30 in the C-group (p = 1.00). Micrometastases (≤2 mm) were retrieved in 5/30 TL-group patients and in 4/30 C-group patients (p = 1.00). Final histology staged as pN1a 10 (33.3%) patients for each group. FSE correctly identified five patients with occult nodal metastases >2 mm (16.6%) in TL-group, who underwent TT plus bilateral CND during the same surgical procedure. No permanent complications occurred. At a mean follow-up of 22.2 months, no local and/or nodal recurrence were observed. CONCLUSIONS: Intraoperative assessment of N status obtained with IpsiCND plus FSE allows for an accurate risk stratification. IpsiCND plus FSE real time modulated thyroidectomy seems a safe and effective surgical strategy reducing the need of a subsequent completion surgery and, theoretically, the risk of local recurrence.

Combined molecular and mathematical analysis of long noncoding RNAs expression in fine needle aspiration biopsies as novel tool for early diagnosis of thyroid cancer.

PURPOSE: In presence of indeterminate lesions by fine needle aspiration (FNA), thyroid cancer cannot always be easily diagnosed by conventional cytology. As a consequence, unnecessary removal of thyroid gland is performed in patients without cancer based on the lack of optimized diagnostic criteria. Aim of this study is identifying a molecular profile based on long noncoding RNAs (lncRNAs) expression capable to discriminate between benign and malignant nodules. METHODS: Patients were subjected to surgery (n = 19) for cytologic suspicious thyroid nodules or to FNA biopsy (n = 135) for thyroid nodules suspicious at ultrasound. Three thyroid-specific genes (TG, TPO, and NIS), six cancer-associated lncRNAs (MALAT1, NEAT1, HOTAIR, H19, PVT1, MEG3), and two housekeeping genes (GAPDH and P0) were analyzed using Droplet Digital PCR (ddPCR). RESULTS: Based on higher co-expression in malignant (n = 11) but not in benign (n = 8) nodules after surgery, MALAT1, PVT1 and HOTAIR were selected as putative cancer biomarkers to analyze 135 FNA samples. Cytological and histopathological data from a subset of FNA patients (n = 34) were used to define a predictive algorithm based on a Naïve Bayes classifier using co-expression of MALAT1, PVT1, HOTAIR, and cytological class. This classifier exhibited a significant separation capability between malignant and benign nodules (P < 0.0001) as well as both rule in and rule out test potential with an accuracy of 94.12% and a negative predictive value (NPV) of 100% and a positive predictive value (PPV) of 91.67%. CONCLUSIONS: ddPCR analysis of selected lncRNAs in FNA biopsies appears a suitable molecular tool with the potential of improving diagnostic accuracy.

Hemithyroidectomy versus total thyroidectomy in the intermediate-risk differentiated thyroid cancer: the Italian Societies of Endocrine Surgeons and Surgical Oncology Multicentric Study.

The surgical treatment of the intermediate-risk DTC (1-4 cm) remains still controversial. We analyzed the current practice in Italy regarding the surgical management of intermediate-risk unilateral DTC to evaluate risk factors for recurrence and to identify a group of patients to whom propose a total thyroidectomy (TT) vs. hemithyroidectomy (HT). Among 1896 patients operated for thyroid cancer between January 2017 and December 2019, we evaluated 564 (29.7%) patients with unilateral intermediate-risk DTC (1-4 cm) without contralateral nodular lesions on the preoperative exams, chronic autoimmune thyroiditis, familiarity or radiance exposure. Data were collected retrospectively from the clinical register from 16 referral centers. The patients were followed for at least 14 months (median time 29.21 months). In our cohort 499 patients (88.4%) underwent total thyroidectomy whereas 65 patients (11.6%) underwent hemithyroidectomy. 151 (26.8%) patients had a multifocal DTC of whom 57 (10.1%) were bilateral. 21/66 (32.3%) patients were reoperated within 2 months from the first intervention (completion thyroidectomy). Three patients (3/564) developed regional lymph node recurrence 2 years after surgery and required a lymph nodal neck dissection. The single factor related to the risk of reoperation was the histological diameter (HR = 1.05 (1.00-1-09), p = 0.026). Risk stratification is the key to differentiating treatment options and achieving better outcomes. According to the present study, tumor diameter is a strong predictive risk factor to proper choose initial surgical management for intermediate-risk DTC.

[Complications in thyroid surgery]. / Complicanze in chirurgia tiroidea.

Thyroidectomy is one of the most frequently performed surgical procedure worldwide, even if the risks of lethal postoperative complications prevented its evolution and diffusion until the beginning of the XX century. At that time, T. Kocher described his meticulous technique, reporting excellent results in terms of mortality and morbidity. At present, mortality for this procedure approaches 0% and overall complication rate is less than 3%. Nonetheless, major complications of thyroidectomy (i.e. compressive hematoma, recurrent laryngeal nerve palsy and hypoparathyroidism) are still fearful complications and account for a significant percentage of medico-legal claims. Patients volume and surgical skill play an important role in reducing the risk of complications. Accurate knowledge of anatomy and pathophysiology, complications incidence and pathogenesis and a careful surgical performance are essential. In this review, post-thyroidectomy complications basing on literature analysis and personal experience are described. The main anatomical, technical and pathophysiological factors that help preventing post-thyroidectomy complications are analyzed, taking into proper account new technologies and the minimally invasive surgical procedures that influenced thyroid surgery during the last decade.

Total thyroidectomy alone versus ipsilateral versus bilateral prophylactic central neck dissection in clinically node-negative differentiated thyroid carcinoma. A retrospective multicenter study.

BACKGROUND: Central neck dissection (CND) remains controversial in clinically node-negative differentiated thyroid carcinoma (DTC) patients. The aim of this multicenter retrospective study was to determine the rate of central neck metastases, the morbidity and the rate of recurrence in patients treated with total thyroidectomy (TT) alone or in combination with bilateral or ipsilateral CND. METHODS: The clinical records of 163 clinically node-negative consecutive DTC patients treated between January 2008 and December 2010 in three endocrine surgery referral units were retrospectively evaluated. The patients were divided into three groups: patients who had undergone TT alone (group A), TT with ipsilateral CND (group B), and TT with bilateral CND (group C). RESULTS: The respective incidences of transient hypoparathyroidism and unilateral recurrent nerve injury were 12.6% and 1% in group A, 23.3% and 3.3% in B, and 36.7% and 0% in C. Node metastases were observed in 8.7% in group A, 23.3% in B, and 63.3% in C. Locoregional recurrence was observed in 3.9% of patients in group A and in 0% in B and C. CONCLUSIONS: We found no statistically significant differences in the rates of locoregional recurrence between the three groups. Therefore, TT appears to be an adequate treatment for these patients; CND is associated with higher rates of transient hypoparathyroidism and cannot be considered the treatment of choice even if it could help for more appropriate selection of patients for RAI. Ipsilateral CND could be an interesting option considering the lower rate of hypocalcemia to be validated by further studies.

Doppler ultrasonography before thyroidectomy is not useful to prevent cerebrovascular accident.

Surgical manipulation of the cervical vascular bundle during neck surgery may promote a thromboembolic event. We evaluated if thyroid surgery is associated with any alterations in the carotid artery wall that would imply an augmented risk of cerebrovascular accident (CVA). A prospective evaluation of a consecutive series of patients who underwent total thyroidectomy was performed. High resolution Doppler ultrasonography (HR-DU) was performed the day before and three days after surgery in asymptomatic consenting patients scheduled for total thyroidectomy. Two hundred patients were recruited. Preoperatively, no hemodynamically significant stenosis (> 70%) was observed. Surgery was delayed in one patient because of asymptomatic subclavian steal syndrome. The remaining 199 patients underwent total thyroidectomy. No modification of preoperative findings was observed at the postoperative HR-DU evaluation. No CVA was observed. In the absence of any significant stenosis, thyroid surgery does not affect the presence and extent of arterial wall disease and the consequent risk of CVA. Thus, screening with HR-DU does not seem beneficial in a generally asymptomatic population without significant risk factors.

Occult papillary carcinoma of the thyroid presenting as a cervical cyst.

BACKGROUND: A cystic neck mass representing metastatic papillary thyroid cancer to a cervical lymph node may be the presenting symptom in patients with an occult papillary cancer of the thyroid. This cystic change can cause diagnostic problems and not infrequently delay identification of the primary thyroid tumor. This study investigates the frequency, treatment, and pathologic features of this entity. METHODS: All clinical charts and microscopic slides of 136 consecutive patients who underwent thyroid operation for papillary carcinoma (PC) from 1990 to 1995 were reviewed. Hematoxylin-and-eosin and immunohistochemical stains (IMHS) for thyroglobulin also were reviewed. RESULTS: Eight patients (5.8%) presented with a cystic neck mass and no palpable thyroid lesion. In all 8 patients, the diagnosis was made by an excision of the cystic neck mass. In 3 patients, the cyst demonstrated classical features of PC, such as papillae and psammoma bodies. In the remaining 5 (62%), only focal papillae or nuclear features of papillary carcinoma were present. A careful review of the histology and IMHS were necessary to arrive at the correct diagnosis in these 5 patients. CONCLUSIONS: Occult papillary cancer of the thyroid presenting as a cystic neck mass is not uncommon and must be considered in the differential diagnosis. Excision and careful review of the histology and IMHS is necessary to prevent delay of the proper diagnosis. Although the thyroid tumor was less than 1 cm and sometimes only microscopic, the extensive nodal metastasis has led us to favor near total or total thyroidectomy and modified neck dissection in this entity.

Is the identification of the external branch of the superior laryngeal nerve mandatory in thyroid operation? Results of a prospective randomized study.

BACKGROUND: The aim of this study was to investigate the incidence of injury to the external branch of the superior laryngeal nerve (EBSLN) with 2 different surgical approaches. METHODS: From 1998 to 2000, 289 consecutive patients undergoing thyroidectomy were randomly divided into 2 groups. In group A (137 patients [215 upper pole ligations]), the superior thyroid artery was ligated after identification of the EBSLN. In group B (152 patients [244 upper pole ligations]), the superior thyroid artery's branches were ligated separately close to the gland. In all patients, a phoniatric evaluation with videostrobolaryngoscopy and spectrographic examination was performed. RESULTS: The 2 groups were well matched regarding age, sex, thyroid pathological findings, and type of operation. In group A, the EBSLN was not clearly identified in 11.6% of cases. Alterations of EBSLN function were absent in both groups of patients, either postoperatively or 1 and 6 months after operation. Group B showed statistically significant shorter operative time compared with that for group A. CONCLUSIONS: Even if the EBSLN often crosses the superior thyroid pedicle, especially in large goiters, this study demonstrated that accurate distal ligation of the branches of the superior thyroid artery is a safe technique to prevent EBSLN injury.

Video-assisted thyroidectomy for papillary thyroid carcinoma.

BACKGROUND: In patients with small papillary thyroid carcinomas (PTC), we evaluated the operative feasibility and safety of video-assisted thyroidectomy (VAT) and the completeness of the surgical resection. METHODS: Video-assisted thyroidectomy was attempted in 24 patients with thyroid malignancy. Total thyroid resection for PTC was achieved completely by VAT in 20 of them, who were included in this study. RESULTS: In this study, 12 total thyroidectomies and 8 lobectomies followed by completion thyroidectomies were performed. Eight patients also underwent central neck lymph node dissection. Mean postoperative serum thyroglobulin was 0.2 ng/ml for patients receiving LT4 suppressive treatment and 4.2 ng/ml for patients after LT4 withdrawal. Postoperative ultrasonography showed no residual thyroid tissue. The mean radioiodine uptake at postoperative scintiscan was 2.2%. CONCLUSIONS: In the case of PTC, VAT is feasible and safe. The completeness of the surgical resection seems comparable with that reported for conventional surgery. Nevertheless, larger series and longer follow-up evaluation are necessary for definitive conclusions to be drawn about its oncologic validity.

[Laparoscopic adrenalectomy in the treatment of malignant adrenal lesions]. / La surrenectomia laparoscopica nel trattamento delle lesioni surrenaliche maligne.

The role of laparoscopic approach for the treatment of malignant adrenal diseases is still controversial. The aim of this study was to verify the results of laparoscopic adrenalectomy in the management of adrenal malignancies. The medical records of all the patients who underwent laparoscopic procedures for adrenal diseases and in whom malignancy was demonstrated at final histology were reviewed. Nine patients were included (3 malignant pheochromocytomas, 4 adrenocortical carcinomas and 2 adrenal metastases). At a mean follow-up of 17.0 +/- 12.8 months (range, 2-36), all but two patients were alive and disease free. One patient died for unrelated causes. No patient developed local or port site recurrence. The results of this study demonstrate that laparoscopic adrenalectomy can be safe and effective also in case of adrenal malignancies. Conversion to open surgery in mandatory in case of local invasion and when the dissection cannot be as accurate as in conventional operations. A preliminary laparoscopic exploration can be planned in case of suspected malignant lesions to confirm the diagnosis and to evaluate their operability.

[Assessment of the adequacy of health services in day hospital care: experience of an endocrine surgery day care unit at a university polyclinic]. / Valutazione di appropriatezza delle prestazioni sanitarie effettuate in regime di Day Hospital: l'esperienza di una unità di DH di chirurgia endocrina in un Policlinico Universitario.

The aim of the study was to assess the appropriateness of the provision of surgical treatment in the day hospital setting and at the same time to evaluate the efficacy of the service provided. The study was conducted on admissions to a day care unit operating in conjunction with the surgery division of a university hospital. The evaluation of appropriateness was carried out using explicit criteria, based on regional regulations and on guidelines drawn up by the Agency for Regional Health Services. The criteria related to the hospital bed equivalent Rotation Index and to the types of DRGs treated and services provided. Efficacy was assessed using the following para-meters: number of US-guided fine needle aspiration biopsies; techniques used; age, sex and nodule size; patient distribution by results of diagnostic examination; cytological classification; percentage of patients with complications. We also evaluated the possibility of transferring short-term (2-3 days) surgical admissions from ordinary regimens to the day care setting. The results of this study yield useful synthetic indicators for assessing the appropriateness both of the day care function as a whole and of individual operating units, providing both administrative and medical staff with a useful frame of reference for the planning of health-care management.

Calcitonin measurement in fine-needle aspirate washouts vs. cytologic examination for diagnosis of primary or metastatic medullary thyroid carcinoma.

Ultrasound-guided fine-needle aspiration biopsy cytology (FNAB-C) is able to detect approximately 63% of medullary thyroid carcinoma (MTC). The measurement of calcitonin in the needle washout (FNAB-CT) could improve its accuracy. Sixty-two FNAB-C were performed in 38 patients. Serum calcitonin (sCT) was measured before performing FNAB-C. After obtaining a FNAB-C specimen, the needle was washed with 0.5 ml of saline solution to obtain the CT washouts. Receiver operating characteristic (RO C) analysis identified the cut-offs of FNAB-CT and FNAB-CT/sCT. Eighteen MTC were found at final histology. RO C analysis indicated FNAB-CT > 10.4 pg/ml and FNABCT/ sCT > 1.39 as more accurate cut-off values. Overall accuracy, positive (PPV) and negative predictive values (NPV) were 85%, 100 and 83%, respectively, for FNAB-C, 97%, 100%, 96% for FNAB-CT and 90%, 83% and 93% for FNAB-CT/sCT. The integration of FNAB-C and FNAB-CT resulted in 98% overall accuracy, 100% PPV and 98% NPV; the integration of FNAB-C and FNAB-CT/sCT in 90% overall accuracy, 80% PPV and 95% NPV. One of 2 false negative FNAB-CT and one of 3 false negative FNAB CT/sCT were correctly diagnosed by FNAB-C. Eight of 9 non-diagnostic FNAB-C were correctly classified by FNAB-CT and 7 by FNAB CT/sCT. FNAB-CT should integrate but not replace FNAB-C. FNAB-CT is particularly useful in the presence of non-diagnostic FNAB-C.

Is there a role for video-assisted parathyroidectomy in regions with high prevalence of goitre?

Minimally-invasive procedures for parathyroidectomy have revolutionized the surgical treatment of primary hyperparathyroidism (pHPT). Coexistence of goitre is considered a major contraindication for these approaches, especially if unilateral. A specific advantage of video-assisted parathyroidectomy (VAP) compared to other endoscopic techniques is the possibility to combine it with thyroidectomy when necessary and when the selection criteria for video-assisted thyroidectomy (VAT) are met. We evaluated the role of VAP in a region with a high prevalence of goitre. The medical records of all patients who underwent parathyroidectomy and concomitant thyroid resection in our Division, between May 1998 and June 2012, were reviewed. Patients who underwent VAP and concomitant VAT were included in this study. Overall, in this period, 615 patients were treated in our Division for pHPT and 227 patients (36.9%) underwent concomitant thyroid resection. Among these, 384 patients were selected for VAP and 124 (32.3%) underwent concomitant VAT (lobectomy in 26 cases, total thyroidectomy in 98). No conversion to conventional surgery was registered. Mean operative time was 66.6 ± 43.6 min. Transient hypocalcaemia was observed in 42 cases. A transient recurrent nerve lesion was registered in one case. No other complications occurred. Final histology showed parathyroid adenoma in all but two cases of parathyroid carcinoma, benign goitre in 119 cases and papillary thyroid carcinoma in the remaining 5 patients. After a mean follow-up of 33.2 months, no persistent or recurrent disease was observed. In our experience, a video-assisted approach for the treatment of synchronous thyroid and parathyroid diseases is feasible, effective and safe at least considering short-term follow-up.

Are brown tumours a forgotten disease in developed countries?

Brown tumours (BT), an expression of osteitis fibrosa cystic due to primary hyperparathyroidism (pHPT), can occasionally be mistaken for malignancy. Among 615 patients who underwent parathyroidectomy for pHPT in our institution, the medical records of three patients affected by BT were reviewed. The first patient underwent surgical removal of the orbital mass for a suspected lachrymal gland neoplasm. The remaining two patients underwent, respectively, leg amputation and femur resection for a suspected bone malignancy. Final histology showed a BT in three cases. All three patients were admitted to our Division and underwent successful parathyroidectomy for parathyroid adenoma in two cases and for parathyroid carcinoma in the remaining case. When faced with an osteolithic bone lesion, complete evaluation of medical history, biochemical and radiographic findings can help to reach a correct diagnosis and avoid unnecessary bone resections.

Minimally-invasive parathyroid surgery.

During the last two decades, several techniques for minimally-invasive parathyroidectomy have been developed, including open approaches (open minimally-invasive parathyroidectomy - OMI P), minimally-invasive radio-guided parathyroidectomy (MI-RP), video-assisted parathyroidectomy (VAP), video-assisted parathyroidectomy through a lateral approach (VAP-LA) and purely endoscopic parathyroidectomy (EP). We have reviewed the pertinent literature, analyzing the indications, outcomes, advantages and disadvantages of the different techniques. Even if the field of minimally-invasive parathyroidectomy is heterogeneous, there is some evidence that minimally-invasive video-assisted parathyroidectomy (MIVAP) should be preferred over OMIP for better cosmetic outcomes, improved visualization of neck structures and control of pain. There is also low-level evidence that MIVAP has some advantages over other purely endoscopic procedures for parathyroidectomy and VAP-LA, in terms of technical difficulties, in addition to the possibility to perform bilateral exploration and associated procedures on the thyroid gland. While the data on medium-term results are encouraging, longer follow-up times are still needed to confirm its safety and rate of cure with respect to conventional surgery. It has been demonstrated that MIVAP is also feasible in secondary and familial hyperparathyroidism, although no conclusive data are available.