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.

Necessity of therapy for post-thyroidectomy hypocalcaemia: a multi-centre experience.

PURPOSE: Hypoparathyroidism is one of the most common and most feared complications of total thyroidectomy (TT). The aim of this study is to detect possible markers that may facilitate early tracing of hypocalcaemia-prone patients in order to reduce clinical cost by optimizing patient discharge and to avoid unnecessary treatment. METHODS: Over an 18-month period, 995 patients, 23 % male and 77 % female, aged 52.9 ± 13.4 years, underwent TT in ten Lombardy hospitals. The following parameters were analyzed: calcaemia before and 12-24 and 48 h after surgery, pre- and post-operative parathyroid hormone (PTH) at 24 h and pre-operative 25OH vitamin D. RESULTS: Mortality was nil and morbidity was 22.4 %. Mean 24-h calcaemia and PTH were 2.17 ± 0.15 mmol/l and 31.81 ± 20.35 pg/ml, respectively; mean 24-h PTH decay was 36.7 ± 34.12 %. Four hundred seventy-three (47.5 %) patients were hypocalcaemic at discharge; 142 of whom had transient hypoparathyroidism that became permanent in 27. Patients developing hypocalcaemia had significantly higher values of PTH and calcium decay. At multiple logistic regression, only 24-h calcium decay, PTH drop and the presence of symptoms and parathyroid auto-grafting were significantly related to hypoparathyroidism. The association of these factors had a 99.2 % negative predictive value (NPV) for the development of hypoparathyroidism. A 70 % PTH drop had a 93.75 NPV for transient hypoparathyroidism. A 12 % calcaemia decay had a 95.7 NPV for hypoparathyroidism. CONCLUSIONS: Hypocalcaemic asymptomatic patients with less than 70 % PTH and 12 % calcaemia decay may be safely discharged without treatment. Symptomatic patients and those with parathyroid grafting should receive calcium and vitamin D.

Management of surgical diseases of thyroid gland indications of the United Italian Society of Endocrine Surgery (SIUEC).

A task force of the United Italian society of Endocrine Surgery (SIUEC) was commissioned to review the position statement on diagnostic, therapeutic and health­care management protocol in thyroid surgery published in 2016, at the light of new technologies, recent oncological concepts, and tailored approaches. The objective of this publication was to support surgeons with modern rational protocols of treatment that can be shared by health-care professionals, taking into account important clinical, healthcare and therapeutic aspects, as well as potential sequelae and complications. The task force consists of 13 members of the SIUEC highly trained and experienced in thyroid surgery. The main topics concern clinical evaluation and preoperative workup, patient preparation for surgery, surgical treatment, non-surgical options, postoperative management, prevention and management of major complications, outpatient care and follow-up.

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.

Primary hyperparathyroidism: can ultrasonography be the only preoperative diagnostic procedure?

PURPOSE: The purpose of our study was to assess the role of ultrasonography (US) before surgical treatment of primary hyperparathyroidism. MATERIALS AND METHODS: We retrospectively evaluated 77 patients (60 women, 17 men; mean age 59 years) with primary hyperparathyroidism who underwent parathyroid US prior to surgery. Sixty-five of 77 (84%) patients had undergone (99m)Tc- sestamibi (MIBI) scintigraphy. The results were correlated with the surgical and histopathological findings. RESULTS: Surgery revealed 85 abnormal parathyroid glands in 77 patients (70 adenomas, 15 hyperplasias). The locations of the parathyroid glands were typical cervical (n=77), thyrothymic ligament (n=3), carotid sheath (n=2), and mediastinum (n=3). In two patients, intrathyroid microadenoma was diagnosed by histopathology. Seventy-four enlarged glands in 64 patients were correctly identified at US. Per-patient sensitivity and positive predictive values, respectively, were 84% (64/76) and 99% (64/65) for US, 68% (44/65) and 100% (44/44) for scintigraphy and 91% (59/65) and 98% (59/60) for both techniques combined. We weighed 63 out of 85 glands, obtaining a value of 1,004+/-1,564 mg; 460 mg (mean+/-standard deviation; median). CONCLUSIONS: Preoperative detection and localisation of enlarged parathyroid glands can be based on US, an inexpensive and widely available method, limiting the use of scintigraphy to those cases with negative and/or doubtful findings on US.

The role of narrow-band imaging in parathyroid surgery: a preliminary evaluation in five parathyroid adenoma cases.

BACKGROUND: Narrow-band imaging uses selective haemoglobin light absorption to emphasise vascular visualisation and capillary networks. OBJECTIVE: This study aimed to evaluate the application of this technique to parathyroid surgery. METHOD: This preliminary evaluation was carried out on five consecutive patients with single parathyroid adenoma being considered for minimally invasive video-assisted parathyroidectomy. The adenomas were checked for narrow-band imaging vascular patterns. Minimally invasive video-assisted parathyroidectomy was then carried out in accordance with our standard protocol. RESULTS: In four out of the five cases, narrow-band imaging integrated the white endoscopic light and direct vision, but in one case narrow-band imaging allowed distinction between the hidden neoplastic tissue and the surrounding structures thanks to the different vascular patterns. CONCLUSION: Narrow-band imaging was helpful in properly identifying adenoma. It is suggested that this technique be considered as a means for surgeons to improve their confidence in selected surgical treatments and to improve treatment quality.

Intra-operative testing for parathyroid hormone: the Central Laboratory option.

BACKGROUND: Intra-operative PTH testing in the operating theatre has proven to be an accurate way to verify the removal of all pathological parathyroid tissue in primary hyperparathyroidism. Its limitation is the high cost. An alternative, more cost-effective procedure is proposed: intra-operative PTH dosage at the Central Laboratory. PATIENTS AND METHODS: Fifty-four patients underwent parathyroidectomy with intraoperative dosage of PTH at the Central Laboratory. Three blood samples were taken from each patient: just after the induction of anesthesia, 5 and 10 min after parathyroidectomy. The samples were sent to the Central Laboratory and analysed simultaneously. The results were phoned back to the theatre. The procedure was considered effective when PTH drop was >/=50% from basal value, 10 min after parathyroidectomy. RESULTS: 98.1% of patients proved recovered (average follow- up 31.1 months). The procedure had 3 false negatives, 1 false positive, with sensitivity, specificity, accuracy, positive predictive value and negative predictive value of 94.0%, 75.0%, 92.6%, 97.9%, and 50.0%, respectively. DISCUSSION AND CONCLUSION: The main disadvantage of the presented procedure is the long waiting time. Nevertheless this time is the same as that required for results from intra-operative histological examination, the only alternative to determine surgery effectiveness in centres where portable instrumentation for intra-operative PTH dosage in the operating theatre is not available. The advantage of intra-operative PTH at the Central Laboratory is the very low cost. If results in terms of sensitivity, specificity, accuracy, and cost are taken into consideration, intra-operative dosage of PTH at the Central Laboratory may be deemed a viable alternative to the operating theatre.

Medullary and papillary carcinoma of the thyroid gland occurring as a collision tumour: report of three cases with molecular analysis and review of the literature.

We report the simultaneous occurrence of medullary thyroid carcinoma (MTC) and papillary thyroid carcinoma (PTC), presenting as spatially distinct and well-defined tumour components, in three cases. In the first patient, histology, immunohistochemistry and electron microscopy demonstrated an MTC in the one nodule and PTC in two additional lesions. Non-neoplastic thyroid parenchyma separated the three nodules. Metastasis from PTC was diagnosed in a regional lymph node. Genetic analysis of both tumour components showed a distinctive mutational pattern: in the MTC a Cys634Arg substitution in exon 11 of the RET gene and in the two PTC foci a Val600Glu substitution in exon 15 of the BRAF gene. The other two patients are members of a large multigenerational family affected with familial MTC due to a germline mutation of the RET gene (Ala891Ser). Both patients harboured, besides medullary cancer and C-cell hyperplasia, distinct foci of papillary thyroid cancer, which was positive for Val600Glu BRAF mutation. Review of the literature disclosed 18 similar lesions reported and allowed the identification of different patterns of clinical presentation and biological behaviour. So far, the pathogenesis of these peculiar cases of thyroid malignancy has been completely unknown, but an underlying common genetic drive has been hypothesised. This is the first report in which two mutations, in the RET and BRAF genes, have been identified in three cases of MTC/PTC collision tumour, thus documenting the different genetic origin of these two coexisting carcinomas.

Radio-guided video-assisted parathyroidectomy: a preliminary report.

BACKGROUND: The surgical management of primary hyperparathyroidism is changing both in terms of the extent of cervical exploration and in technique. There are many new mini-invasive procedures for neck surgery. We describe our preliminary experience with a technique that combines two mini-invasive procedures--radio-guided and video-assisted parathyroidectomy. METHODS: Six consecutive patients with no recurrent or persistent primary hyperparathyroidism, no previous cervical operations, and no thyroid pathologies were selected to undergo radio-guided video-assisted parathyroidectomy. RESULTS: One case was converted. There was no morbidity or mortality in the postoperative period. Six parathyroids were removed; the histological diagnosis was adenoma in all cases. All patients were discharged on the 1st postoperative day. Calcium serum levels normalized in all cases, with only one case of transient postoperative hypocalcemia. All patients were normocalcemic after 6 months. CONCLUSION: Radio-guided video-assisted parathyroidectomy is feasible in selected patients. However, longer follow-up and more cases are necessary before this procedure can be applied routinely.

Mixed follicular and parafollicular thyroid carcinoma.

A rare case of mixed follicular-parafollicular thyroid carcinoma which occurred in a 50-year-old man, is reported. The ultrastructural aspects of the tumor showed: a biphasic growth pattern with microfolliculi and solid areas; the coexpression of thyroglobulin and calcitonin antigens in the same follicle-like structures; the presence of neuroendocrine granules, microvilli and intracytoplasmic canaliculi bordered by microvilli. These characteristics lead us to a diagnosis of mixed follicular-parafollicular thyroid carcinoma.

Post-thyroidectomy hypocalcemia and feasibility of short-stay thyroid surgery.

AIM: To study the feasibility of thyroid surgery in a short-stay hospitalization regimen, with particular reference to postoperative hypocalcemia. METHODS: The clinical files of 696 patients operated on from January 1977 to January 2000 for thyroid diseases were analyzed. They were divided into groups on the basis of extent of operation and type of disease. Hypocalcemia incidence was compared between the different groups of patients. Data were analyzed statistically using the chi-square and Fisher's exact tests. RESULTS: There were 74 temporary (10.6%) and 12 (1.7%) persistent hypocalcemia cases. None of these occurred in patients undergoing lobectomy. The incidence of hypocalcemia was higher in two-lobe vs. single-lobe operations (p < 0.05), in total thyroidectomy with lymphadenectomy vs. total thyroidectomy (p < 0.05) and in hyperthyroidism vs. patients with normal serum hormone levels (p < 0.05). 84.9% of hypocalcemia cases developed on postoperative day 1, with only one tetanic crisis. CONCLUSIONS: Thyroid surgery in the short-stay hospitalization regimen is feasible for all patients undergoing lobectomy. Patients undergoing subtotal or total thyroidectomy may be treated in a short-stay regimen, only if they are affected with non-hyperfunctioning benign diseases and if they have normal serum calcium levels on postoperative day 1.

[Follicular neoplasm of the thyroid: usefulness of extemporaneous histologic study of frozen sections]. / Neoplasia follicolare della tiroide: utilità dell'esame istologico estemporaneo al congelatore.

PURPOSE: The role of frozen section (FS) in determining thyroidectomy extent in patients with follicular neoplasms is debated. The Authors consider FS usefulness through experience retrospective review. MATERIAL AND METHODS: From January 1980 to June 1999, 1252 Fine Needle Aspirations (FNA) were performed in patients with thyroid nodules. Out of these, 155 (12.4%) resulted follicular neoplasms. All these patients were operated on: 54 had total thyroidectomy because of both lobes disease and 101 had emithyroidectomy with FS. FS results were compared to definitive histological examination. Sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of frozen section have been estimated. RESULTS: Out of 155 follicular neoplasms, 15 resulted malignant at definitive histological examination: 6 were diagnosed by FS. All 6 patients had a total thyroidectomy during the same operation. Of the rimanenti 9, 6 had a second operation for radicalization within 2-3 days. FS sensitivity was 42.9%, specificity 100%, accuracy 92.0%, PPV 100% and NPV 8.5%. DISCUSSION: Some Authors consider FS useful because it allows to radicalize the operation immediately, in case of positivity for malignancy. Even if only few patients, the possibility to solve the problem in a one-step procedure is a great advantage. Other Authors consider FS useless because to diagnose a poor number malignant neoplasms, a lot of intra-operative examination have to be done. Costs are higher than benefits. CONCLUSIONS: The Authors believe that both attitudes are correct and the decision of using or not FS cannot be standardized.

[Pneumocystosis of splenic localization in the course of HIV infection: a new indication for splenectomy. Description of a case]. / Pneumocistosi a localizzazione splenica in corso di infezione da HIV: una nuova indicazione alla splenectomia. Descrizione di un caso.

Pneumocystis carinii is a common cause of interstitial pneumonitis in AIDS patients: it affects 85% of patients with cell-mediated immunodeficiencies. Extrapulmonary infection is much more infrequent and it is observed only in these patients who receive aerosolized pentamidine prophylaxis because of minimal systemic distribution of the drug. No case of extrapulmonary disease was observed in patients receiving systemic prophylaxis for Pneumocystis carinii with cotrimoxazole. The pathogenesis of extrapulmonary infection is not clear: it is probably connected with hematogenous or lymphatic dissemination from the lung. In a small number of case is due to reactivation of extrapulmonary foci or to a new infection. The management of disseminated infection of Pneumocystis carinii is medical: only recently a combination of medical and surgical approach was proposed for a patient with extrapulmonary infection. We report a case of 29 years old patient with AIDS with a demonstrated pulmonary and splenic localisation of pneumocystis carinii submitted to surgical splenectomy. The surgical decision was taken for several reasons: no response to medical therapy, the relative good general condition of the patient despite the immunological status, the presence of thrombocytopenia and abdominal pain in the left upper quadrant, and the risk of rupture of spleen. The post-operative course was eventful. We support splenectomy for splenic infection of Pneumocystis carinii in very small selected cases and only with palliative intent.

Increased muscle expression of interleukin-17 in Duchenne muscular dystrophy.

OBJECTIVES: Duchenne muscular dystrophy (DMD) is a degenerative muscle wasting disease caused by mutations in the dystrophin gene. Dystrophic muscle is characterized by chronic inflammation, and inflammatory mediators could be promising targets for innovative therapeutic interventions. We analyzed muscle biopsy samples of DMD-affected children to characterize interleukin (IL)-17 and Forkhead box P3 (Foxp3) expression levels and to identify possible correlations with clinical status. METHODS: Expression levels of IL-17, Foxp3, tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), IL-6, and transforming growth factor-ß (TGF-ß) were analyzed by real-time PCR in muscle biopsy samples from patients with DMD (n = 27) and juvenile dermatomyositis (JDM) (n = 8). Motor outcome of patients with DMD was evaluated by North Star Ambulatory Assessment score. RESULTS: In DMD, we found higher levels of IL-17 and lower levels of Foxp3 mRNA compared with those for a typical inflammatory myopathy, JDM. Moreover, the IL-17/Foxp3 ratio was higher in DMD than in JDM biopsy samples. IL-17 mRNA levels appeared to be related to the expression levels of other proinflammatory cytokines (TNF-α and MCP-1) and significantly associated with clinical outcome of patients. CONCLUSIONS: The association of IL-17 expression with levels of other inflammatory cytokines and with the clinical course of DMD suggests a possible pathogenic role of IL-17.