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.

Protocolo de evaluación neuropsicológica para adultos en cirugía de la epilepsia / Neuropsychological assessment protocol for adults in epilepsy surgery

INTRODUCCIÓN: La epilepsia refractaria conlleva la intratabilidad de las crisis, por lo que una de las intervenciones que permiten su eliminación o la disminución del número de crisis es la neurocirugía. DESARROLLO: Se plantea la propuesta de un modelo de evaluación neuropsicológica dirigida a la medición del rendimiento cognitivo de pacientes adultos candidatos a cirugía de la epilepsia. Se propone un protocolo abierto, en consonancia con las propuestas más señaladas en los distintos centros de referencia para la epilepsia, dirigido a la obtención de una línea de base del rendimiento cognitivo global, la reserva cognitiva y la dominancia manual, así como procesos cognitivos como la atención, el lenguaje, las habilidades visuoconstructivas y manipulativas, la memoria y las funciones ejecutivas, entre otros, sin prescindir de la exploración psicopatológica y la calidad de vida del paciente, de forma que permita contribuir, junto con los resultados de otras especialidades diagnósticas, a la localización y minimización de las secuelas cognitivas secundarias a la intervención quirúrgica sobre el foco epiléptico, así como a la facilitación de información al equipo médico responsable del caso y a pacientes y familiares sobre las posibilidades y el pronóstico de la intervención. Es necesario disponer de un arsenal de técnicas y contar con un adecuado consenso a la hora de realizar la valoración de los datos obtenidos. CONCLUSIONES: Se propone un modelo de evaluación que permite obtener información del perfil neuropsicológico del paciente candidato a cirugía de la epilepsia, abierto a la discusión y que sirva de modelo para el debate al resto de centros de referencia de la epilepsia

INTRODUCTION: Refractory epilepsy means that the seizures are untreatable, and therefore one of the interventions that makes it possible to eliminate them or to accomplish a reduction in the number of seizures is neurosurgery. DEVELOPMENT: A neuropsychological evaluation model aimed at measuring the cognitive performance of adult patients who are candidates for epilepsy surgery is proposed. In line with the proposals most frequently put forward by the various reference centres for epilepsy, an open protocol is proposed that is aimed at obtaining a baseline of overall cognitive performance, cognitive reserve and manual dominance, as well as cognitive processes such as attention, language, visuoconstructive and manipulative skills, memory and executive functions, among others, without neglecting the psychopathological examination and the patient's quality of life. This, together with the results of other diagnostic specialities, will contribute to the localisation and minimisation of the cognitive sequelae secondary to the surgical intervention on the epileptic focus, as well as to providing information to the medical team responsible for the case and to patients and relatives about the possibilities and prognosis of the intervention. It is necessary to have a battery of techniques and an adequate consensus when evaluating the data obtained. CONCLUSIONS: An assessment model is proposed that allows information to be obtained about the neuropsychological profile of the candidate for epilepsy surgery, which is open to debate and serves as a model for discussion by the other epilepsy reference centres

[Neuropsychological assessment protocol for adults in epilepsy surgery]. / Protocolo de evaluación neuropsicológica para adultos en cirugía de la epilepsia.

INTRODUCTION: Refractory epilepsy means that the seizures are untreatable, and therefore one of the interventions that makes it possible to eliminate them or to accomplish a reduction in the number of seizures is neurosurgery. DEVELOPMENT: A neuropsychological evaluation model aimed at measuring the cognitive performance of adult patients who are candidates for epilepsy surgery is proposed. In line with the proposals most frequently put forward by the various reference centres for epilepsy, an open protocol is proposed that is aimed at obtaining a baseline of overall cognitive performance, cognitive reserve and manual dominance, as well as cognitive processes such as attention, language, visuoconstructive and manipulative skills, memory and executive functions, among others, without neglecting the psychopathological examination and the patient's quality of life. This, together with the results of other diagnostic specialities, will contribute to the localisation and minimisation of the cognitive sequelae secondary to the surgical intervention on the epileptic focus, as well as to providing information to the medical team responsible for the case and to patients and relatives about the possibilities and prognosis of the intervention. It is necessary to have a battery of techniques and an adequate consensus when evaluating the data obtained. CONCLUSIONS: An assessment model is proposed that allows information to be obtained about the neuropsychological profile of the candidate for epilepsy surgery, which is open to debate and serves as a model for discussion by the other epilepsy reference centres.

TITLE: Protocolo de evaluación neuropsicológica para adultos en cirugía de la epilepsia.Introducción. La epilepsia refractaria conlleva la intratabilidad de las crisis, por lo que una de las intervenciones que permiten su eliminación o la disminución del número de crisis es la neurocirugía. Desarrollo. Se plantea la propuesta de un modelo de evaluación neuropsicológica dirigida a la medición del rendimiento cognitivo de pacientes adultos candidatos a cirugía de la epilepsia. Se propone un protocolo abierto, en consonancia con las propuestas más señaladas en los distintos centros de referencia para la epilepsia, dirigido a la obtención de una línea de base del rendimiento cognitivo global, la reserva cognitiva y la dominancia manual, así como procesos cognitivos como la atención, el lenguaje, las habilidades visuoconstructivas y manipulativas, la memoria y las funciones ejecutivas, entre otros, sin prescindir de la exploración psicopatológica y la calidad de vida del paciente, de forma que permita contribuir, junto con los resultados de otras especialidades diagnósticas, a la localización y minimización de las secuelas cognitivas secundarias a la intervención quirúrgica sobre el foco epiléptico, así como a la facilitación de información al equipo médico responsable del caso y a pacientes y familiares sobre las posibilidades y el pronóstico de la intervención. Es necesario disponer de un arsenal de técnicas y contar con un adecuado consenso a la hora de realizar la valoración de los datos obtenidos. Conclusiones. Se propone un modelo de evaluación que permite obtener información del perfil neuropsicológico del paciente candidato a cirugía de la epilepsia, abierto a la discusión y que sirva de modelo para el debate al resto de centros de referencia de la epilepsia.

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.

A novel CDC73 gene mutation in an Italian family with hyperparathyroidism-jaw tumour (HPT-JT) syndrome.

PURPOSE: The CDC73 gene, encoding parafibromin, has been identified as a tumour suppressor gene both in hyperparathyroidism-jaw tumour (HPT-JT) syndrome and in sporadic parathyroid carcinoma. While the vast majority of CDC73 mutations affect the N-terminus or the central core of the encoded protein, as yet few mutations have been reported affecting the C-terminus. Here, we report a case (Caucasian female, 28 years) with an invasive ossifying fibroma of the left mandible and hyperparathyroidism (sCa = 16 mg/dl, PTH = 660 pg/mL) due to a parathyroid lesion of 20 mm, hystologically diagnosed as carcinoma. METHODS: The whole CDC73 gene was screened for the presence of mutations by Sanger sequencing. Immunohistochemistry, in vitro functional assays, Western blotting, MTT assays and in-silico modelling were performed to assess the effect of the detected mutation. RESULTS: Sequence analysis of the CDC73 gene in the proband revealed the presence of a novel deletion affecting the C-terminus of the encoded protein (c.1379delT/p.L460Lfs*18). Clinical and genetic analyses of the available relatives led to the identification of three additional carriers, one of whom was also affected by a parathyroid lesion. Immunohistochemistry, Western blotting, MTT and in-silico modelling assays revealed that the deletion leads to down-regulation of the mutated protein, most likely through a proteasome-mediated pathway. We also found that the deletion may cause a conformational change in the C-terminus of the protein, possibly affecting its interaction with partner proteins. Finally, we found that the mutant protein enhances cellular growth. CONCLUSIONS: We report a novel mutation in the CDC73 gene that may underlie HPT-JT syndrome. This mutation appears to affect the C-terminal moiety of the encoded protein, which is thought to interact with other protein partners. The identification of these partners may be instrumental for our understanding of the CDC73-associated phenotype.

Diagnostic, therapeutic and healthcare management protocols in parathyroid surgery: II Consensus Conference of the Italian Association of Endocrine Surgery Units (U.E.C. CLUB).

AIM: To update the Diagnostic-Therapeutic-Healthcare Protocol (Protocollo Diagnostico-Terapeutico-Assistenziale, PDTA) created by the U.E.C. CLUB (Association of the Italian Endocrine Surgery Units) during the I Consensus Conference in 2008. METHODS: In the preliminary phase, the II Consensus involved a selected group of experts; the elaboration phase was conducted via e-mail among all members; the conclusion phase took place during the X National Congress of the U.E.C. CLUB. 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. CONCLUSIONS: The PDTA for parathyroid surgery approved by the II Consensus Conference (June 2013) is the official PDTA of the U.E.C. CLUB.

[Neck dissection for Head and Neck cancers: state of the art and classification]. / Dissezioni linfonodali del collo per tumori del distretto cervico-facciale: note introduttive e classificazione.

The purposes of this article are to review the history and evolution of neck dissections, including an update on node levels and their anatomical landmark. A number of classification systems were proposed and subsequently established for neck dissection procedures. The system most often employed was published in 1991 by the American Head and Neck Society and American Academy of Otolaryngology- Head and Neck Surgery and revised in 2002 and 2008. According to this classification, neck dissections are grouped into four broad categories: radical neck dissection (RND), modified radical neck dissection (MRND), selective neck dissection (SND) and extended neck dissection (ERND). The choice between different surgeries depends on type and site of head and neck tumor as well nodal involvement.

A decrease of calcitonin serum concentrations less than 50 percent 30 minutes after thyroid surgery suggests incomplete C-cell tumor tissue removal.

CONTEXT AND OBJECTIVES: The prognosis of medullary thyroid carcinoma (MTC) depends on the completeness of the first surgical treatment. To date, it is not possible to predict whether the tumor has been completely removed after surgery. The aim of this study was to evaluate the reliability of an intraoperative calcitonin monitoring as a predictor of the final outcome after surgery in patients with MTC. PATIENTS AND METHODS: Twenty patients underwent total thyroidectomy and central lymph node dissection on the basis of a positive pentagastrin test. In six cases a preoperative diagnosis of MTC was achieved at the cytological examination. During the surgical intervention, calcitonin was measured at the time of anesthesia, at the time of manipulation, and 10 and 30 min after surgical excision. At the histological examination, 10 patients had MTC and 10 had C cell hyperplasia. RESULTS: As compared with calcitonin levels before thyroidectomy, a decrease of calcitonin greater than 50% 30 min after surgery was able to significantly distinguish patients who were cured from those who experienced persistence of disease. It was not possible to find a similar result when the decrease of calcitonin 10 min after surgery was considered. CONCLUSIONS: A rate of calcitonin decrease less than 50% 30 min after thyroidectomy plus central neck lymph node dissection suggests the persistence of tumor tissue in patients operated for MTC. These results indicate that intraoperative calcitonin monitoring may be a useful tool to predict the completeness of surgery in patients with MTC.

Predictive value of pentagastrin test for preoperative differential diagnosis between C-cell hyperplasia and medullary thyroid carcinoma in patients with moderately elevated basal calcitonin levels.

BACKGROUND AND OBJECTIVES: Medullary thyroid carcinoma (MTC) is a calcitonin (CT)-secreting neuroendocrine tumour originating from thyroid C cells. Serum CT concentrations are helpful in the early detection of MTC, while it is still unclear whether they can be used also for the differential diagnosis between MTC and C-cell hyperplasia (CCH), a precancerous condition in familial MTCs but with unclear clinical significance in sporadic MTCs. Nowadays, surgery is recommended in all patients with basal or pentagastrin (PG)-stimulated CT value of 100 pg/ml or more, without discriminating if they are affected with MTC or CCH only. The objective of this study was to investigate the utility of the PG test for CT in distinguishing CCH from MTC before surgery. PATIENTS AND METHODS: Sixteen of 20 patients with thyroid nodules and basal CT levels between 15 and 100 ng/l had a positive PG test (>100 ng/l PG CT peak) and form the basis of the data analysis. A diagnosis of MTC was histologically proved on surgical samples in seven patients and of CCH in nine other patients. Four patients with neither FNAB nor PG test consistent with a diagnosis of MTC did not undergo thyroidectomy. RESULTS: A peak of CT of 275 ng/l after PG was able to significantly distinguish patients with MTC from patients with CCH, with 100% sensitivity and 89% specificity (P = 0.002). PG-stimulated calcitonin levels >275 ng/l had a positive predictive value (PPV) value for diagnosis of MTC of 100%, and PG-stimulated calcitonin levels <275 had a PPV for the diagnosis of CCH of 89%. CONCLUSIONS: A CT cut-off after PG of 275 ng/l is suggested to be highly predictive in distinguishing CCH from MTC before surgery, and this may be helpful in selecting patients for thyroid surgery.

Cervical vagal schwannoma. A case report.

Schwannoma originating from the cervical vagus nerve is an extremely rare neoplasm. Vagal nerve schwannoma usually occurs between the third and fifth decades of life, it does not show sex predilection both sexes being equally affected and it most often presents as a painless, slow-growing, lateral neck mass. The treatment of choice is complete surgical excision with preservation of the neural pathway, when it is possible. These tumours, in fact, are almost always benign and a conservative surgical approach is emphasized by most of the Authors. A case of a cervical vagal schwannoma, in a 33-year old male with a previous medical history of malignant lymphoma, is described. The clinical features, diagnosis, management and pathological findings of cervical vagal schwannoma are discussed.

Secretive and proliferative tumor profile helps to select the best imaging technique to identify postoperative persistent or relapsing medullary thyroid cancer.

In patients with postoperative persistent medullary thyroid cancer (MTC), the tumor detection rate is generally low for most of the imaging techniques now available. The aim of this study was to investigate if the clinico-biological profile of the tumor may indicate which imaging technique to perform in order to identify postoperative persistent or relapsing MTC foci. Thirty-five consecutive MTC patients with detectable and progressively increasing postoperative serum concentrations of calcitonin were enrolled in the study. The detection rates of 18F-deoxy-d-glucose (FDG)-positron emission tomography (PET), somatostatin receptor scintigraphy (SRS), and 131I-metaiodobenzylguanidine scintigraphy (MIBG) were compared in relation with calcitonin and carcinoembryonic antigen serum concentrations, Ki-67 score and results of conventional imaging techniques (CIT). FDG-PET positivity was significantly associated with calcitonin serum concentrations >400 pg/ml and Ki-67 score >2.0% (P<0.05), while SRS positivity was associated with calcitonin serum concentrations >800 pg/ml (P<0.05). SRS positivity significantly correlated with tumor appearance at CIT (P<0.01), while FDG-PET was positive in nine CIT-negative patients. The secretive and proliferative tumor profile may guide the choice of the imaging technique to use in the follow-up of patients with MTC. A Ki-67 score >2.0% suggests to perform a FDG-PET in addition to conventional imaging. Calcitonin secretion predicts both FDG-PET and SRS uptake but SRS positivity is generally found only in patients with well defined MTC lesions that are also detectable at the conventional imaging examination. MIBG outcome is not predicted by any clinico-biological factors here investigated.

Coherent delocalization of atomic wave packets in driven lattice potentials.

Atomic wave packets loaded into a phase-modulated vertical optical-lattice potential exhibit a coherent delocalization dynamics arising from intraband transitions among Wannier-Stark levels. Wannier-Stark intraband transitions are here observed by monitoring the in situ wave-packet extent. By varying the modulation frequency, we find resonances at integer multiples of the Bloch frequency. The resonances show a Fourier-limited width for interrogation times up to 2 s. This can also be used to determine the gravity acceleration with ppm resolution.

Merkel cell carcinoma: experience of 14 cases and literature review.

Merkel cell carcinoma is an aggressive skin cancer, with a significant incidence of locoregional lymphnode involvement, which requires timely diagnosis, adequate staging and aggressive therapy based essentially on surgical procedures. The aim of this study is to report our experience and to compare our results with literature findings, in order to discuss the role of the procedures adopted and their influence on prognosis. From July 1995 to April 2005, 14 patients were treated and followed-up for MCC in the National Cancer Institute of Naples. Tumor location was: buttocks (43%), extremities (36%) head (7%), unknown (14%). There were 7 Stage I, 5 Stage II and 2 Stage III patients. Surgical treatment consisted in wide excision (WE) in Stage I cases, WE and regional lymphadenectomy followed by radio- or chemo-therapy in Stage II and combined surgical and pre- and post-operative medical treatments in Stage III. Overall disease specific survival rate was 64% (median follow up 44 months). Recurrence occurred in 86% of Stage I and 20% of Stage II patients and involved, in 83.3% of Stage I patients, the lymph nodal draining basin. The treatment of recurrence implied surgery and radio or radiochemotherapy. Overall survival rate of recurrent patients was 57% (median follow-up 37.2 months). Due to the particular lymphotrophism of MCC, major care should be set on investigation and treatment of tumor lymph nodal draining basin. As long as the disease remains surgically manageable the prognosis for patients with MCC is favourable. The role of radio and chemotherapy is not yet assessed.

Released momentum distribution of a Fermi gas in the BCS-BEC crossover.

We develop a time-dependent mean-field theory to investigate the released momentum distribution and the released energy of an ultracold Fermi gas in the BCS-BEC crossover after the scattering length has been set to zero by a fast magnetic-field ramp. For a homogeneous gas we analyze the nonequilibrium dynamics of the system as a function of the interaction strength and of the ramp speed. For a trapped gas the theoretical predictions are compared with experimental results.

[Histophenotypical variants of squamous cell carcinoma of the skin]. / Varianti istofenotipiche di carcinoma squamocellulare della cute.

Cutaneous squamous cell carcinoma (SCC) is, in its most frequent presentation, a moderately aggressive neoplastic disease. It can, however, present in a moltitude of clinico-pathological variants, some of which are characterized by a more malignant attitude. It is important to determine which tumors, among the various histophenotypes, are high risk in order to establish the appropriate treatment and follow-up. Histologic subtype has been considered as a possible variable in determining the prognosis of cutaneous SCC. We report our experience with 3 cases of peculiar variants of cutaneous SCC.

[Role of lymphadenectomy in the treatment of Merkel-cell tumors in i and ii stages]. / Ruolo della linfoadenectomia nel trattamento del tumore a cellule di merkel in stadio i e ii.

Merkel cell carcinoma (MCC) is a rare, malignant skin cancer, exhibiting neuroendocrine differentiation, with a significant incidence of locoregional lymph nodal involvement (40%-73%). The accepted staging system classifies MCC as: stage I, localized skin disease; stage II, regional lymph node disease; stage III, metastatic disease. The clinical differentiation of stage I and II patients is difficult and understaging is frequent. Surgery, as first approach, represents the leading treatment for this neoplasm and, depending on stage consists in: local wide excision for stage I patients and local excision and lymphadenectomy for stage II. In our experience, lymphadenectomy, included in the initial treatment of all stage II patients, seemed to influence positively the prognosis. In comparing stage related recurrence and survival rates the results we obtained were better in stage II patients, where lymphadenectomy was included in the initial treatment than in stage I subjects, who received local excision alone as first treatment and lymphadenectomy as secondary treatment for nodal recurrence (overall recurrence rate 86% vs 20%, survival rate 71% vs 80% in stage I vs stage II patients). The performance of lymphadenectomy for stage I MCC could be reconsidered both for a more reliable staging of the disease and for a positive impact on recurrence and survival rates.

HLA allele frequency and clinical outcome in Italian patients with cutaneous melanoma.

The current study focuses the analysis on the possible relationship between HLA allele frequency and clinical outcome of melanoma in a population of 382 Italian patients, as compared with 203 ethnically matched controls. In a 3-year follow-up study, results showed significant differences between groups of patients selected according to clinical stage, histology, and progression of the disease. A*01 seems to be correlated with a less aggressive variant of the disease, whereas DRB1*01-DQB1*0501 seems to be associated with metastatic progression of melanoma. Moreover, a negative association with B*13, B*44, as well as with DRB1*04-DQB1*0302 was found. A multivariate logistic regression model showed HLA-DRB1*04 to behave as an independent favorable prognostic marker of melanoma in our population (OR = 2.34, CI = 1.15-4.74).

Sentinel lymph node biopsy in patients with cutaneous melanoma: outcome after 3-year follow-up.

AIMS: The management of patients with cutaneous melanoma in the absence of lymph-node metastases is still controversial. The experience of the National Cancer Institute in Naples was analysed to evaluate the 3-year disease free survival and overall survival for all patients submitted to sentinel node biopsy (SNB). METHODS: Data from 265 sentinel biopsies performed in the last five years were reviewed to determine the effect of the treatment on disease free survival and overall survival stratified the patients for node status and tumour ulceration. RESULTS: Statistical analysis showed a 3-year survival advantage for sentinel node negative patients compared to sentinel node positive cases with a 88.4 and 72.9%, respectively (p < 0.05). CONCLUSIONS: SNB provides an accurate staging of nodal status in patients with melanoma in the absence of clinical evidence of metastases. Longer follow-up and final results from multicenter selective lymphadenectomy (MSLT) are needed to clarify the role of this procedure.