Tiziana Cavalli

Multiple endocrine neoplasia type 1 (MEN1): Not only inherited endocrine tumors

Abstract: MEN 1 is a rare hereditary cancer syndrome which manifests a variety of endocrine and non-endocrine neoplasms and lesions. Growing knowledge of this condition in both its molecular genetic underpinnings and its clinical implications have affected the entire spectrum of the clinical management of MEN patients. The MEN1 gene is a tumor suppressor gene, and mutations in it account for the development of the MEN1 clinical syndrome through impairment of several cell functions, such as cell proliferations, cell growth control, apoptosis, DNA replication and repair, gene expression, transcriptional machinery control, and hormone secretion. Currently, DNA testing makes possible the early identification of germline mutations in asymptomatic mutation carriers. The ever increrasing combination of genetic and clinical tools will allow early detection of MEN1-associated neoplasms, potentially improving clinical outcomes and quality of life for both affected patients and their relatives.

Hereditary hyperparathyroidism syndromes.

Primary hyperparathyroidism is a common endocrine disorder, resulting from a persistent hypercalcemia along with an inadequate secretion of parathyroid hormone. In approx 95% of cases, it occurs sporadically; rarely, it is part of familial syndromes. These inherited syndromes typically present at an earlier age than the nonheritable form and occur with equal frequencies in both sexes. The differential diagnosis is often difficult, but it is of fundamental importance for the management of patients and their family. The availability of specific genetic tests has improved the diagnostic accuracy allowing early diagnosis in asymptomatic family members. Before the advent of genetic testing, a definitive diagnosis could be made only in symptomatic cases based on clinical data and family history.

DNA-based test: when and why to apply it to primary hyperparathyroidism clinical phenotypes

Several cancer‐related genes have been discovered and molecular test for the cancer genetic risk assessment has been widely increasing. Disorders such as Multiple Endocrine Neoplasia syndromes have received benefits from the identification of the responsible genes whose mutations account for the genetic susceptibility to develop endocrine tumours. Primary hyperparathyroidism (PHPT)is a clinical phenotype frequently associated to Multiple Endocrine Neoplasia syndromes, but it can also represent the unique endocrinopathy recurring as a familial cluster. In recent years, care options have been made available to patients and families with hereditary PHPT, and the process of systematically assessing the genetic risk has been becoming increasingly important. This review aims to help health providers not frequently dealing with genetic testing use and it will introduce some general concepts concerning genetic diagnosis issues. As an example the role and the practical usefulness of DNA‐based diagnosis in patients affected by different forms of congenital PHPT is described, with a close look on why, when and how genetic testing should be performed in these subjects and their relatives. Some practical recommendations and suggestions concerning on how to deal when a suspect or known case of familial PHPT has to be faced conclude this manuscript.

Peripheral quantitative computed tomography (pQCT) for the assessment of bone strength in most of bone affecting conditions in developmental age: a review

Peripheral quantitative computed tomography provides an automatical scan analysis of trabecular and cortical bone compartments, calculating not only their bone mineral density (BMD), but also bone geometrical parameters, such as marrow and cortical Cross-Sectional Area (CSA), Cortical Thickness (CoTh), both periosteal and endosteal circumference, as well as biomechanical parameters like Cross-Sectional Moment of Inertia (CSMI), a measure of bending, polar moment of inertia, indicating bone strength in torsion, and Strength Strain Index (SSI). Also CSA of muscle and fat can be extracted. Muscles, which are thought to stimulate bones to adapt their geometry and mineral content, are determinant to preserve or increase bone strength; thus, pQCT provides an evaluation of the functional ‘muscle-bone unit’, defined as BMC/muscle CSA ratio. This functional approach to bone densitometry can establish if bone strength is normally adapted to the muscle force, and if muscle force is adequate for body size, providing more detailed insights to targeted strategies for the prevention and treatment of bone fragility. The present paper offers an extensive review of technical features of pQCT and its possible clinical application in the diagnostic of bone status as well as in the monitoring of the skeleton’s health follow-up.

In vitro effects of oestrogens, antioestrogens and SERMs on pancreatic solid pseudopapillary neoplasm-derived primary cell culture

Background: Solid-pseudopapillary neoplasms of the pancreas (SPNs) are uncommon tumours usually frequent in young women. Although the pathogenesis of SPNs is uncertain a potential influence of the sex hormone milieu on the biology of these tumours has been suggested. The controversial expression of oestrogen receptors (ERs) in SPNs, provide a rationale for studying the effects of oestrogenic molecules on SPN development. Methods: The expression of a large series of hormonal ligands and receptors was evaluated in tissue specimens and in a primary cell culture (SPNC), obtained from a SPN in young female patient. The effects of 17β-oestradiol (17βE2), ICI 182,780 and tamoxifen (Tam) on cell replication and growth were examined. Results: We have established SPNC primary line. Immunocytochemical analysis was positive for vimentin, cyclin D1 and β-catenin and negative for cytokeratin, CD10 and neuroendocrine markers, in line with the immunostaining features of the tumoral tissue. Expression of ERα, ERβ and progesterone mRNAs was demonstrated in SPNC and tumor tissue. A proliferative and antiproliferative action of 17βE2 and Tam respectively were proved in SPNC. Conclusions: In conclusion, we provide the first direct evidence that oestrogenic molecules can influence proliferation of SPNC, offering future strategies in the control of this neoplasia via selective ER modulators.

A multidisciplinary approach to desmoid tumors. When intra-abdominal fibromatosis degenerates into an abscess, which is the right treatment?

INTRODUCTION Desmoid tumors are rare benign tumors that originates in the fibrous sheath or musculo-aponeurotic structure. Histologically benign, they tends to invade locally and to be recurrent. PRESENTATION OF CASE We report a rare case of an intra-abdominal desmoid tumor in a patient affected by familial adenomatous polyposis, which degenerated into abscess. Male, 38 years, was hospitalized for abdominal pain, bowel obstruction and fever. The computed tomography showed a big dishomogeneous mass occupying the whole mesentery with internal massive liquefaction. The mass extended from the epigastrium for 13cm up to L3. On the right mesogastric side a solid, thick mass of about 2cm, with a length of 4.5cm, was identified; it was not cleavable from the wall and from some of the loops. We decided to perform a computed tomography-guided percutaneous drainage. Two hundred ml of purulent necrotic material was aspirated, and washing with antibiotic solution was carried out. Cytological examination of fluid drainage showed histiocytes and neutrophils. At follow-up, the patients clinical condition had improved. An abdominal ultrasound showed a substantial reduction in the diameter of the mass. DISCUSSION Diagnosis and treatment of desmoids tumor in patients with familial adenomatous polyposis may be difficult, especially when desmoids are located intra-abdominally and in the mesentery. Seldom will desmoid tumors be complicated by abscess formation. CONCLUSION The management of desmoids tumors is not easy and the choice of the best treatment may be difficult due to the different possible anatomical presentations.

Surgery in MEN 2A Patients Older Than 5 Years with Micro-MTC: Outcome at Long-term Follow-up

In multiple endocrine neoplasia syndrome type 2A (MEN 2A), early total thyroidectomy (TT; performed before the age of 5 years) is the best option to prevent medullary thyroid carcinoma (MTC) development, but the management of MEN 2A patients diagnosed after childhood is still under debate. Seventeen consecutive patients diagnosed with MEN 2A after the age of 5 years (mean age, 23.3 years) with a pathologic diagnosis of micro-MTC without nodal involvement were enrolled. All patients underwent TT with thymectomy and central compartment lymph node dissection. During surgery, parathyroid tissue removal occurred in 14 patients. No major postoperative complications nor persistent hypoparathyroidism was observed. After a mean follow-up of 16.6 years, no patient developed primary hyperparathyroidism or disease recurrence. Even if TT is recommended before the age of 5, when MEN 2A diagnosis is performed after this age in micro-MTC without nodal involvement, TT with thymectomy and central compartment lymphadenectomy can provide good oncologic and functional results.

Role of Acupuncture in the Management of Severe Acquired Brain Injuries (sABIs)

Acupuncture therapy has been used to treat several disorders in Asian countries and its use is increasing in Western countries as well. Current literature assessed the safety and efficacy of acupuncture in the acute management and rehabilitation of patients with neurologic disorders. In this paper, the role of acupuncture in the treatment of acute severe acquired brain injuries is described, acting on neuroinflammation, intracranial oedema, oxidative stress, and neuronal regeneration. Moreover, beneficial effects of acupuncture on subacute phase and chronic outcomes have been reported in controlling the imbalance of IGF-1 hormone and in decreasing spasticity, pain, and the incidence of neurovegetative crisis. Moreover, acupuncture may have a positive action on the arousal recovery. Further work is needed to understand the effects of specific acupoints on the brain. Allegedly concurrent neurophysiological measurements (e.g., EEG) may help in studying acupuncture-related changes in central nervous system activity and determining its potential as an add-on rehabilitative treatment for patients with consciousness disorders.

Massive intrathoracic lipoma in men1 syndrome.

Introduction The multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant syndrome characterized by the onset of hyperparathyroidism, gastroenteropancreatic neuroendocrine tumors and pituitary lesions. Presentation of case This appears to be the first described case of a massive intrathoracic lipoma in MEN1. The patient was affected with primary hyperparathyroidism treated with a total parathyroidectomy followed by a distal pancreatectomy for insulinoma. At follow-up, the computed tomography showed a massive lesion on the left emithorax suggestive of a lipoma. At the onset of a mild dyspnea we decided to perform the surgical excision of the mass obtaining a complete relief of the symptoms. Discussion This case is evidence of the importance of a strict follow-up of such patients. Conclusion Lipomas are the most frequent benign soft tissue tumors. They are usually sporadic but are sometimes related to hereditary syndromes. Intrathoracic localizations are rare and can arise mainly in the mediastinum, bronchus or lung. The diagnosis is often incidental; despite preoperative imaging will accurately show the features of the lesions, it is impossible obtain an accurate diagnosis-hence, the treatment of choice remains the surgical excision.

Genetic Aspects of Hereditary Hyperparathyroidism

Primary hyperparathyroidism (PHPT) is a frequent endocrine disorder of adulthood, diagnosed by the presence of both high levels of circulating parathyroid hormone, produced by one or more enlarged parathyroid glands, and hypercalcemia. Although it can occur at any age, it is mostly reported in the sixth decade of life.