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1. An update on the use of inositols in preventing gestational diabetes mellitus (GDM) and neural tube defects (NTDs)

Author

Facchinetti, F, Cavalli, P, Copp, Aj, D'Anna, R, Kandaraki, E, Greene, Nde, Unfer, V, Experts Group on Inositol in Basic and Clinical Research (Facchinetti, F, Appetecchia, M, Aragona, C, Bertelli, M, Bevilacqua, A, Bezerra Espinola MS, Bizzarri, M, Copp, A, D’Anna, R, Dewailly, D, Greene, N, Hernández Marín, I, Kamenov, Za, Diamanti-Kandarakis, E, Laganà, As, Monastra, G, Montanino Oliva, M, Nestler, Je, Ozay, Ac, Papalou, O, Pkhaladze, L, Porcaro, G, Prapas, N, Soulage, Co, Stringaro, A, Vazquez-Levin, M, and Wdowiak, A

Subjects
medicine.medical_specialty, endocrine system diseases, D-chiro-inositol (DCI), medicine.medical_treatment, Toxicology, 030226 pharmacology & pharmacy, Article, gestational diabetes mellitus (GDM), 03 medical and health sciences, 0302 clinical medicine, Insulin resistance, prevention, Pregnancy, insulin resistance, Medicine, Animals, Humans, Insulin, Neural Tube Defects, neural tube defects (NTDs), Pharmacology, Fetus, business.industry, Obstetrics, Diabetes, Neural tube, Infant, Newborn, nutritional and metabolic diseases, Infant, General Medicine, medicine.disease, Newborn, Gestational diabetes, Diabetes, Gestational, myo-inositol (MI), medicine.anatomical_structure, 030220 oncology & carcinogenesis, Obstetric history, Gestational, Female, Inositol, business, Maternal body
Abstract

INTRODUCTION: Obstetric history and maternal body composition and lifestyle may be associated with serious complications both for the mother, such as gestational diabetes mellitus (GDM), and for the fetus, including congenital malformations such as neural tube defects (NTDs). AREAS COVERED: In view of the recent knowledge, changes of nutritional and physical activity habits ameliorate glycemic control during pregnancy and in turn improve maternal and neonatal health outcomes. Recently, a series of small clinical and experimental studies indicated that supplementation with inositols, a family of insulin sensitizers, was associated with beneficial impact for both GDM and NTDs. EXPERT OPINION: Herein, we discuss the most significant scientific evidence supporting myo-inositol administration as a prophylaxis for the above-mentioned conditions.

Published
2020

2. Acromegaly is associated with increased cancer risk: a survey in Italy

Author

Terzolo, Massimo, Reimondo, Giuseppe, Berchialla, Paola, FERRANTE, EMANUELE, Malchiodi, Elena, De Marinis, Laura, Pivonello, Rosario, Grottoli, Silvia, Losa, Marco, Cannavo, Salvatore, Ferone, Diego, Montini, Marcella, Bondanelli, Marta, De Menis, Ernesto, Martini, Chiara, Puxeddu, Efisio, Velardo, Antonino, Peri, Alessandro, Faustini-Fustini, Marco, Tita, Patrizia, Pigliaru, Francesca, Peraga, Giulia, Borretta, Giorgio, Scaroni, Carla, Bazzoni, Nicoletta, Bianchi, Antonio, Berton, Alessandro, Serban, Andreea Liliana, Baldelli, Roberto, Fatti, Letizia Maria, Colao, Annamaria, Arosio, Maura, Lombardi, G., TRIMARCHI, LORENZO, Degli Uberti, E. C., Ambrosio, M. R., Pagani, G., Attanasio, R., Kara, E., Mantero, F., Ceccato, F., Mortini, P., Razzore, P., Angeletti, G., Della Torre, D., Mariotti, S., Ghigo, E., Mainini, A. L., Appetecchia, M., Vigneri, R., Minuto, F., Nazzari, E., Cavagnini, F., Persani, L., Terzolo, Massimo, Reimondo, Giuseppe, Berchialla, Paola, Ferrante, Emanuele, Malchiodi, Elena, De Marinis, Laura, Pivonello, Rosario, Grottoli, Silvia, Losa, Marco, Cannavo, Salvatore, Ferone, Diego, Montini, Marcella, Bondanelli, Marta, De Menis, Ernesto, Martini, Chiara, Puxeddu, Efisio, Velardo, Antonino, Peri, Alessandro, Faustini-Fustini, Marco, Tita, Patrizia, Pigliaru, Francesca, Peraga, Giulia, Borretta, Giorgio, Scaroni, Carla, Bazzoni, Nicoletta, Bianchi, Antonio, Berton, Alessandro, Serban, Andreea Liliana, Baldelli, Roberto, Fatti, Letizia Maria, Colao, Annamaria, Arosio, Maura for the Italian Study Group of Acromegaly, Arosio, Maura, Lombardi, G., Trimarchi, Lorenzo, Degli Uberti, E. C., Ambrosio, M. R., Pagani, G., Attanasio, R., Kara, E., Mantero, F., Ceccato, F., Mortini, P., Razzore, P., Angeletti, G., Della Torre, D., Mariotti, S., Ghigo, E., Mainini, A. L., Appetecchia, M., Vigneri, R., Minuto, F., Nazzari, E., Cavagnini, F., and Persani, L.

Subjects
Adult, Male, Cancer Research, medicine.medical_specialty, Colorectal cancer, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, NO, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Risk Factors, Neoplasms, Internal medicine, Gh IGF1, Acromegaly, Humans, Medicine, cancer, Family history, Thyroid cancer, Acromegaly cancer, Oncology, business.industry, GH, IGF1, acromegaly, Incidence, Risk Factor, Incidence (epidemiology), Cancer, Middle Aged, medicine.disease, Diabetes and Metabolism, Acromegaly, cancer, GH, IGF1, Italy, 030220 oncology & carcinogenesis, Neoplasm, Female, Cohort Studie, business, Kidney cancer, Human, Cohort study
Abstract

It is debated if acromegalic patients have an increased risk to develop malignancies. The aim of the present study was to assess the standardized incidence ratios (SIRs) of different types of cancer in acromegaly on a large series of acromegalic patients managed in the somatostatin analogs era. It was evaluated the incidence of cancer in an Italian nationwide multicenter cohort study of 1512 acromegalic patients, 624 men and 888 women, mean age at diagnosis 45 ± 13 years, followed up for a mean of 10 years (12573 person-years) in respect to the general Italian population. Cancer was diagnosed in 124 patients, 72 women and 52 men. The SIRs for all cancers was significantly increased compared to the general Italian population (expected: 88, SIR 1.41; 95% CI, 1.18–1.68, P P = 0.022), kidney cancer (SIR 2.87; 95% CI, 1.55–5.34, P P

Published
2017

3. Assessment of the awareness and management of sleep apnea syndrome in acromegaly. The COM.E.TA (Comorbidities Evaluation and Treatment in Acromegaly) Italian Study Group

Author

Menis, E., Giustina, A., Colao, A., Degli Uberti, E., Ghigo, E., Minuto, F., Bogazzi, F., Drigo, R., Cattaneo, A., Aimaretti, G., Ambrosio, M. R., Andreani, M., Angeletti, G., Celleno, R., Appetecchia, M. L., Baldelli, R., Armigliato, M., Arosio, M., Babini, A., Baldi, F., Balza, G., Bartalena, L., Tanda, M. L., Battista, C., Beck-Peccoz, P., Boffano, G. M., Martino, E., Borboni, P., Borretta, G., Baffoni, C., Boscaro, M., Arnaldi, G., Buschini, M., Salvatore Cannavo, Caramellino, A., Carani, C., Castelli, A., Pancotti, M., Cavagnini, F., Chiodera, P., Cataldo, S., Chiovato, L., Colombo, M., Crivellaro, C., D Ulizia, M., Mattè, S., Del Monte, P., Delitala, G., Masala, A., Fabbri, A., Piantoni, L., Faustini Fustini, M., Favro, S., Ferone, D., Fidotti, E., Valentini, F., Formoso, G., Frigato, F., Furlani, L., Gargiulo, P., Gasparoni, P., Gazzaruso, C., Giordano, C., Giorgino, F., Grandi, M., Pedersoli, S., Grimaldi, F., Grottoli, S., La Grotta, A., Lanzi, R., Limone, P., Razzore, P., Lio, S., Lo Cascio, V., Francia, G., Davì, M. V., Lo Coco, R., Macinini, E., Mantero, F., Scaroni, C., Marchetti, M., Mariotti, S., Pigliaru, F., Marzullo, P., Monachesi, M., Montini, M., Pagani, G., Muggeo, M., Castello, R., Mulas, G., Nassi, R., Vezzosi, C., Nizzoli, M., Orlandi, F., Pacini, F., Di Cairano, G., Palermo, M., Paoletta, A., Papini, E., Parillo, M., Parisi, G., Pasquali, R., Pagotto, U., Pavoncello, S., Perego, M. R., Peri, A., Piscopello, L., Pivonello, R., Raffa, M., Raggiunti, B., Roiter, I., Tamburrano, G., Terzolo, M., Testa, I., Testori, G., Cerruti, N., Toscano, V., Tota, N., Vailati, A., Lovati, E., Valcavi, R., Vincenzi, V., De Menis, E, Giustina, A, Colao, A, Degli Uberti, E, Ghigo, E, Minuto, F, Bogazzi, F, Drigo, R, Cattaneo, A, Aimaretti, G, Giordano, C, Giustina, Andrea, Italian Study Group, C. O. M. E. T. A., De Menis, E., Giustina, A., Colao, A., Degli Uberti, E., Ghigo, E., Minuto, F., Bogazzi, F., Drigo, R., Cattaneo, A., Aimaretti, G., Ambrosio, M.R., Andreani, M., Angeletti, G., Celleno, R., Appetecchia, M.L., Baldelli, R., Armigliato, M., Arosio, M., Babini, A., Baldi, F., Balza, G., Bartalena, L., Tanda, M.L., Battista, C., Beck-Peccoz, P., Boffano, G.M., Martino, E., Borboni, P., Borretta, G., Baffoni, C., Boscaro, M., Arnaldi, G., Buschini, M., Cannavò, S., Caramellino, A., Carani, C., Castelli, A., Pancotti, M., Cavagnini, F., Chiodera, P., Cataldo, S., Chiovato, L., Colombo, M., Crivellaro, C., D'Ulizia, M., De Mattè, S., Del Monte, P., Delitala, G., Masala, A., Fabbri, A., Piantoni, L., Faustini Fustini, M., Favro, S., Ferone, D., Fidotti, E., Valentini, F., Formoso, G., Frigato, F., Furlani, L., Gargiulo, P., Gasparoni, P., Gazzaruso, C., Giordano, C., Giorgino, F., Grandi, M., Pedersoli, S., Grimaldi, F., Grottoli, S., La Grotta, A., Lanzi, R., Limone, P., Razzore, P., Lio, S., Lo Cascio, V., Francia, G., Davì, M.V., Lo Coco, R., Macinini, E., Mantero, F., Scaroni, C., Marchetti, M., Mariotti, S., Pigliaru, F., Marzullo, P., Monachesi, M., Montini, M., Pagani, G., Muggeo, M., Castello, R., Mulas, G., Nassi, R., Vezzosi, C., Nizzoli, M., Orlandi, F., Pacini, F., Di Cairano, G., Palermo, M., Paoletta, A., Papini, E., Parillo, M., Parisi, G., Pasquali, R., Pagotto, U., Pavoncello, S., Perego, M.R., Peri, A., Piscopello, L., Pivonello, R., Raffa, M., Raggiunti, B., Roiter, I., Tamburrano, G., Terzolo, M., Testa, I., Testori, G., Cerruti, N., Toscano, V., Tota, N., Vailati, A., Lovati, E., Valcavi, R., Vincenzi, V., Colao, Annamaria, and C. O. M. E. T. A. Italian Study G. r. o. u., P.

Subjects
Male, Pediatrics, medicine.medical_specialty, medicine.medical_treatment, Endocrinology, Diabetes and Metabolism, Polysomnography, Comorbidity, somatostatin analogs, acromegaly, sleep apnea syndrome, Settore MED/13 - Endocrinologia, Somatostatin analog, Endocrinology, Sleep Apnea Syndromes, Quality of life, Acromegaly, Sleep apnea syndrome, Somatostatin analogs, Physicians, Surveys and Questionnaires, medicine, Prevalence, Humans, Continuous positive airway pressure, medicine.diagnostic_test, business.industry, Sleep apnea, Awareness, Focus Groups, sleep apnea, medicine.disease, Sleep Apnea, Italy, Physical therapy, COM.E.TA, Female, Clinical Competence, business
Abstract

In 2007 the Italian COM.E.T.A. (COMorbidities Evaluation and Treatment in Acromegaly) study group started to assess the application in a clinical setting of the Versailles criteria for management of acromegaly complications by a first questionnaire focusing on cardiovascular co-morbidities. A further questionnaire on sleep apnea syndrome (SAS) was delivered by the COM.E.T.A. study group to 107 endocrine centers in Italy. The results of our survey suggest that SAS is a well-known comorbidity even if its estimated prevalence is lower than in the literature. Polysomnography is the preferred tool for diagnosis. Control of SAS is considered relevant both for quality of life and co-morbidities. Continuous positive airway pressure is the cornerstone of therapy, but patients' acceptance may be critical. Control of GH/IGF-I secretion is important to improve SAS. Management of SAS requires cooperation between specialists. ©2011, Editrice Kurtis.

Published
2011

4. Hurthle cell tumours of the thyroid. Personal experience and review of the literature

Author

Agnese Barnabei, Ferretti, E., Baldelli, R., Procaccini, A., Spriano, G., and Appetecchia, M.

Subjects
Adult, Male, Adenoma, Oxyphilic, Humans, Female, Thyroid Neoplasms, Original Articles, Middle Aged, Prognosis, Aged, Retrospective Studies
Abstract

Hurthle cell carcinoma represents about 5% of differentiated thyroid carcinomas. The prognosis of the malignant type of the tumour is still under debate as some Authors have reported that Hurthle cell adenoma occasionally behaves like Hurthle cell carcinoma. Aim of the present study was to evaluate previously reported data and personal experience on the clinical and pathological features of patients affected by Hurthle cell tumour that may predict disease progression and death. In the literature, factors potentially associated with decreased survival were identified and include: age, disease stage, tumour size, extra-glandular invasion, lymph node disease, distant metastases, extensive surgery, radioiodine treatment. From 1992 to 2003, the Authors identified 28 patients affected by Hurthle cell tumour, 9 with Hurthle cell adenoma and 19 with Hurthle cell carcinoma. Of these, 22 were females and 6 males. Mean age of patients affected by adenoma was 49.7 years (range 30-72) vs. 49.3 years (range 15-72) in Hurthle cell carcinoma patients. In all patients, total thyroidectomy was performed. At histology, 9 adenomas, 5 "minimally invasive" and 14 invasive carcinomas were found. Post-operatively, in Hurthle cell carcinoma patients, TNM staging showed 9 patients with stage I, 5 stage II, 4 stage III and one stage IVa (UICC, 2002). All invasive carcinomas underwent (131)I therapy (91-585 mCi). One Hurthle cell carcinoma patient received external beam radiotherapy. The mean follow-up period was 62 months (range 6-324). Relapse was not observed in any of the cases with adenoma. Only one Hurthle cell carcinoma patient showed distant lung metastases at 60 months' follow-up. In conclusion, Hurthle cell carcinoma was not found to present a more aggressive behaviour than follicular carcinoma, when risk factors, including extent of tumour invasion, were taken into account. None of the patients with Hurthle cell adenoma showed a relapse or death caused by the tumour.

Published
2009

5. Assessment of the awareness and management of cardiovascular complications of acromegaly in Italy. The COM.E.T.A. (COMorbidities Evaluation and Treatment in Acromegaly) Study

Author

Giustina, A., Mancini, T., Boscani, P. F., De Menis, E., Degli Uberti, E., Ghigo, E., Martino, E., Minuto, F., Colao, A., Comorbidities Evaluation, Com E. T. A., Treatment Inacromegaly Italian Study Group, Aimaretti, G., Ambrosio, M. R., Andreani, M., Angeletti, G., Appetecchia, M. L., Armigliato, M., Arnaldi, G., Arosio, M., Babini, A., Baldi, F., Balza, G., Barbaro, D., Bartalena, L., Battista, C., Bechi, R., Beck Peccoz, P., Bellastella, A., Bevilacqua, M., Boccuzzi, G., Boffano, G. M., Bondanelli, M., Borretta, G., Boscaro, M., Buschini, M., Campanini, M., Cannavo, S., Carani, C., Carpenito, F., Carzaniga, C., Castelli, A., Cavagnini, F., Chiarini, V., Chiodera, P., Colombo, M., Colombo, P., Coppola, A., Cozzi, R., Crivellaro, C., D'Antonio, R., Davi, M., De Marinis, L., De Matte, S., De Remigis, P., Del Monte, P., Delitala, G., Doveri, G., D'Ulizia, M., Favro, S., Ferone, D., Fidotti, E., Formoso, G., Francia, G., Frigato, F., Furlani, L., Galuzzo, A., Gargiulo, P., Gasperoni, P., Gazzaruso, C., Giorgino, F., Grandi, M., Grimaldi, F., Indovina, S., Lanzi, R., Legovini, P., Limone, P., Liuzzi, A., Lo Cascio, V., Lo Coco, R., Loli, P., Mantero, F., Marchetti, M., Mariotti, S., Masala, A., Meringolo, D., Monachesi, M., Montini, M., Moretti, C., Muggeo, M., Mulas, G., Nizzolo, M., Oleandri, S., Orio, F., Orlandi, F., Pacini, F., Palermo, M., Pancotti, D., Paoletta, A., Papini, E., Parillo, M., Parisi, G., Pasquali, R., Pavoncello, S., Perego, M. R., Peri, A., Peri, D., Piantoni, L., Raffa, M., Raggiunti, B., Resmini, E., Rizzi, G., Rosatello, A., Rosato, F., Savino, L., Scaroni, C., Sinisi, A., Stefani, I., Tamburrano, G., Tanda, M., Terzolo, M., Testa, I., Testa, R., Testori, G., Toscano, Vincenzo, Tota, N., Travaglini, P., Vailati, A., Valcavi, R., Ventre, I., Vincenzi, W., Vitale, G., A., Giustina, T., Mancini, P. F., Boscani, E., de Meni, E., degli Uberti, E., Ghigo, E., Martino, F., Minuto, Colao, Annamaria, Giustina A, Mancini T, Boscani PF, de Menis E, degli Uberti E, Ghigo E, Martino E, Minuto F, Colao A, Aimaretti G, Ambrosio MR, Andreani M, Angeletti G, Appetecchia ML, Armigliato M, Arnaldi G, Arosio M, Babini A, Baldi F, Balza G, Barbaro D, Bartalena L, Battista C, Bechi R, Beck-Peccoz P, Bellastella A, Bevilacqua M, Boccuzzi G, Boffano GM, Bondanelli M, Borretta G, Boscaro M, Buschini M, Campanini M, Cannavò S, Carani C, Carpenito F, Carzaniga C, Castelli A, Cavagnini F, Chiarini V, Chiodera P, Colombo M, Colombo P, Coppola A, Cozzi R, Crivellaro C, D'Antonio R, Davì M, De Marinis L, De Mattè S, De Remigis P, Del Monte P, Delitala G, Doveri G, D'Ulizia M, Favro S, Ferone D, Fidotti E, Formoso G, Francia G, Frigato F, Furlani L, Galuzzo A, Gargiulo P, Gasperoni P, Gazzaruso C, Giorgino F, Grandi M, Grimaldi F, Indovina S, Lanzi R, Legovini P, Limone P, Liuzzi A, Lo Cascio V, Lo Coco R, Loli P, Mantero F, Marchetti M, Mariotti S, Masala A, Meringolo D, Monachesi M, Montini M, Moretti C, Muggeo M, Mulas G, Nizzolo M, Oleandri S, Orio F, Orlandi F, Pacini F, Palermo M, Pancotti D, Paoletta A, Papini E, Parillo M, Parisi G, Pasquali R, Pavoncello S, Perego MR, Peri A, Peri D, Piantoni L, Raffa M, Raggiunti B, Resmini E, Rizzi G, Rosatello A, Rosato F, Savino L, Scaroni C, Sinisi A, Stefani I, Tamburrano G, Tanda M, Terzolo M, Testa I, Testa R, Testori G, Toscano V, Tota N, Travaglini P, Vailati A, Valcavi R, Ventre I, Vincenzi W, Vitale G., Giustina, Andrea, Mancini, T, Boscani, Pf, DE MENIS, E, DEGLI UBERTI, E, Ghigo, E, Martino, E, Minuto, F, Colao, A, and Italian Study Group, C. O. M. E. T. A.

Subjects
Questionnaires, cardiovascular risk, medicine.medical_specialty, Pathology, Ambulatory blood pressure, Cardiomyopathy, Endocrinology, Diabetes and Metabolism, MEDLINE, Disease, heart, Comorbidity, Left ventricular hypertrophy, NO, Endocrinology, Patient Education as Topic, Surveys and Questionnaires, Acromegaly, medicine, Humans, Intensive care medicine, Awareness, Echocardiography, Hypertension, Questionnaire, business.industry, Cardiovascular Diseases, Epidemiologic Studies, Follow-Up Studies, medicine.disease, Blood pressure, Heart failure, business
Abstract

Background: During the course of acromegaly, cardiovascular, respiratory, and metabolic co-morbidities contribute to enhanced mortality. In 2002, the Pituitary Society and the European Neuroendocrine Association sponsored a Consensus Workshop in Versailles during which guidelines for diagnosis and treatment of co-morbidities in acromegaly were defined. However, as for other guidelines previously issued in the field, no data are available on their clinical application. Aim: The aim of this work coordinated by the Italian Study group on co-morbidities evaluation and treatment in acromegaly (COM.E.T.A.) was to assess, on a national basis, the application in the clinical practice of the Versailles criteria for diagnosis and treatment of cardiovascular comorbities in acromegaly. Materials and methods: In January 2007 an ad hoc designed questionnaire was sent by mail to 130 endocrine Centers in Italy. Results: The guidelines have been generally well perceived and translated in clinical practice. Specifically: 1) echocardiography is considered the mainstay for the diagnosis and follow-up; 2) ambulatory blood pressure monitoring and blood lipid assessment are performed in most hypertensive patients; 3) most endocrinologists directly manage hypertension and are aware of the uncertainty of the effect of the control of the disease on blood pressure levels; 4) ACE inhibitors and angiotensin receptors blockers are first-choice anti-hypertensive treatment; 5) approximately half of the centers consider somatostatin analogues of paramount relevance for biochemical control of disease; 6) awareness that left ventricular hypertrophy and heart failure are the most relevant cardiovascular complications is high although the impact of ischemic, arrhythmic, and valvular complications on prognosis is less well perceived. Conclusion: The results of the present survey suggest that previuosly issued guidelines are generally carefully followed in the clinical practice. On the other side, a certain lack of awareness of emerging aspects of the cardiovascular comorbities of acromegaly confirms the necessity of periodically updating the guidelines based on the availability of new clinical information.

Published
2008

6. Malignant glucagonoma. New options of treatment

Author

Appetecchia, M., Elisabetta Ferretti, Carducci, M., Izzo, F., Carpanese, L., Marandino, F., and Terzoli, E.

Subjects
Time Factors, Glucagonoma, Interferon-alpha, Glucagon, Octreotide, Proglucagon, Immunohistochemistry, Neuroendocrine Tumors, Chromogranins, Chromogranin A, Humans, Female, Tomography, X-Ray Computed, Aged
Abstract

Few cases of malignant glucagonomas have been described in the literature. In this paper we present a case of a 77-year-old woman with necrolytic migratory erythema and high plasma glucagon and chromogranin A levels caused by a neuroendocrine tumour. An abdominal CT scan suggested a pancreatic lesion and two liver metastases. The patient underwent pancreatic debulking and liver metastasectomy. Histological and immunohistochemical investigations revealed a well differentiated neuroendocrine tumour with vascular invasion and scattered immunopositivity for somatostatin receptors. The patient was treated with octreotide (20 mg i.m. every 28 days) for three years without side effects. Three months after surgery symptoms of disease recurred accompanied by hyperglucagonaemia and newly diagnosed liver lesions. The patient was treated with octreotide (30 mg i.m. every 28 days) and interferon-alpha (6 MU s.cc 3 times per week) plus three cycles of hepatic chemoembolisation. Symptoms resolved after the first month of therapy, hormone levels decreased compared to untreated levels and metastatic growth slowed as observed by radiographic evidence. The patient is now asymptomatic with persistent hepatic disease and normal serum glucagon levels forty months after primary treatment. So far, only few immunohistochemical studies are reported on malignant glucagonoma and combined treatment schedules. We demonstrated, for the first time, a scattered immunopositivity for somatostatin receptors in a malignant glucagonoma. For this reason, the somatostatin analogs therapy was instituted. A combined antiproliferative medical treatment and the hepatic chemoembolization have been able to control tumor growth and disease symptoms for a long time after surgery.

7. Real-World Study of Everolimus in Advanced Progressive Neuroendocrine Tumors

Author

Francesca Lugli, Maria Chiara Zatelli, G. Delle Fave, Marialuisa Appetecchia, A. Zaniboni, Alfredo Berruti, Maria Pia Brizzi, Davide Pastorelli, Gabriele Luppi, Giacomo Cartenì, Antongiulio Faggiano, Marco Merlano, Elisabetta Nobili, Carmen Nuzzo, Silvana Chiara, Francesca Spada, C. Funaioli, Francesco Panzuto, Nicola Fazio, Annalisa Fontana, A. Colao, Maria Rosaria Ambrosio, Ferdinando Riccardi, Lorenzo Antonuzzo, Davide Campana, Alfredo Cassano, F. de Braud, Stefano Cascinu, Maria Rinzivillo, Sara Pusceddu, Massimo Falconi, Paola Tomassetti, Panzuto F, Rinzivillo M, Fazio N, de Braud F, Luppi G, Zatelli MC, Lugli F, Tomassetti P, Riccardi F, Nuzzo C, Brizzi MP, Faggiano A, Zaniboni A, Nobili E, Pastorelli D, Cascinu S, Merlano M, Chiara S, Antonuzzo L, Funaioli C, Spada F, Pusceddu S, Fontana A, Ambrosio MR, Cassano A, Campana D, Cartenì G, Appetecchia M, Berruti A, Colao A, Falconi M, Delle Fave G, Panzuto, F, Rinzivillo, M, Fazio, N, de Braud, F, Luppi, G, Zatelli, Mc, Lugli, F, Tomassetti, P, Riccardi, F, Nuzzo, C, Brizzi, M1, Faggiano, Antongiulio, Zaniboni, A, Nobili, E, Pastorelli, D, Cascinu, S, Merlano, M, Chiara, S, Antonuzzo, L, Funaioli, C, Spada, F, Pusceddu, S, Fontana, A, Ambrosio, Mr, Cassano, A, Campana, D, Cartenì, G, Appetecchia, M, Berruti, A, Colao, Annamaria, Falconi, M, and Delle Fave, G.

Subjects
Compassionate Use Trials, Male, Oncology, carcinoid, Cancer Research, medicine.medical_specialty, Drug-Related Side Effects and Adverse Reactions, medicine.medical_treatment, Carcinoid Tumor, Neuroendocrine tumors, Pharmacology, Octreotide, Gastroenterology, Disease-Free Survival, Neuroendocrine, Pancreatic tumors, Everolimus, Internal medicine, Gastrointestinal Cancer, medicine, Humans, Adverse effect, Aged, Neoplasm Staging, Sirolimus, Chemotherapy, business.industry, everolimu, Middle Aged, medicine.disease, NEUROENDOCRINE TUMOURS, Discontinuation, Pancreatic Neoplasms, Neuroendocrine Tumors, Tolerability, Radionuclide therapy, Female, Erratum, business, PANCREATIC ENDOCRINE TUMOR, medicine.drug
Abstract

Everolimus is a valid therapeutic option for neuroendocrine tumors (NETs); however, data in a real-world setting outside regulatory trials are sparse. The aim of this study was to determine everolimus tolerability and efficacy, in relation to previous treatments, in a compassionate use program. A total of 169 patients with advanced progressive NETs treated with everolimus were enrolled, including 85 with pancreatic NETs (pNETs) and 84 with nonpancreatic NETs (non-pNETs). Previous treatments included somatostatin analogs (92.9%), peptide receptor radionuclide therapy (PRRT; 50.3%), chemotherapy (49.7%), and PRRT and chemotherapy (22.8%). Overall, 85.2% of patients experienced adverse events (AEs), which were severe (grade 3–4) in 46.1%. The most frequent severe AEs were pneumonitis (8.3%), thrombocytopenia (7.7%), anemia (5.3%), and renal failure (3.5%). In patients previously treated with PRRT and chemotherapy, a 12-fold increased risk for severe toxicity was observed, with grade 3–4 AEs reported in 86.8% (vs. 34.3% in other patients). In addition, 63.3% of patients required temporarily everolimus discontinuation due to toxicity. Overall, 27.8% of patients died during a median follow-up of 12 months. Median progression-free survival (PFS) and overall survival (OS) were 12 months and 32 months, respectively. Similar disease control rates, PFS, and OS were reported in pNETs and non-pNETs. In the real-world setting, everolimus is safe and effective for the treatment of NETs of different origins. Higher severe toxicity occurred in patients previously treated with systemic chemotherapy and PRRT. This finding prompts caution when using this drug in pretreated patients and raises the issue of planning for everolimus before PRRT and chemotherapy in the therapeutic algorithm for advanced NETs.

Published
2014
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8. Predictors of morbidity and mortality in acromegaly: an Italian survey

Author

M Arosio, G Reimondo, E Malchiodi, P Berchialla, A Borraccino, L De Marinis, R Pivonello, S Grottoli, M Losa, S Cannavò, F Minuto, M Montini, M Bondanelli, E De Menis, C Martini, G Angeletti, A Velardo, A Peri, M Faustini-Fustini, P Tita, F Pigliaru, G Borretta, C Scaroni, N Bazzoni, A Bianchi, M Appetecchia, F Cavagnini, G Lombardi, E Ghigo, P Beck-Peccoz, A Colao, M Terzolo, Arosio, M, Reimondo, G, Malchiodi, E, Berchialla, P, Borraccino, A, De Marinis, L, Pivonello, Rosario, Grottoli, S, Losa, M, Cannavò, S, Minuto, F, Montini, M, Bondanelli, M, De Menis, E, Martini, C, Angeletti, G, Velardo, A, Peri, A, Faustini Fustini, M, Tita, P, Pigliaru, F, Borretta, G, Scaroni, C, Bazzoni, N, Bianchi, A, Appetecchia, M, Cavagnini, F, Lombardi, Gaetano, Ghigo, E, Beck Peccoz, P, Colao, Annamaria, Terzolo, M., Arosio, M., Reimondo, G., Malchiodi, E., Berchialla, P., Borraccino, A., De Marinis, L., Pivonello, R., Grottoli, S., Losa, M., Cannavò, S., Minuto, F., Montini, M., Bondanelli, M., De Menis, E., Martini, C., Angeletti, G., Velardo, A., Peri, A., Faustini-Fustini, M., Tita, P., Pigliaru, F., Borretta, G., Scaroni, C., Bazzoni, N., Bianchi, A., Appetecchia, M., Cavagnini, F., Lombardi, G., Ghigo, E., Beck-Peccoz, P., and Colao, A.

Subjects
Adult, Male, medicine.medical_specialty, Multivariate analysis, acromegaly, IGF-I, Mortality, Prognosi, Endocrinology, Diabetes and Metabolism, morbidity, Disease, Follow-Up Studie, Endocrinology, Risk Factors, Retrospective Studie, Internal medicine, Diabetes mellitus, Acromegaly, Epidemiology, medicine, Humans, Multicenter Studies as Topic, Insulin-Like Growth Factor I, Retrospective Studies, business.industry, Human Growth Hormone, Data Collection, Risk Factor, Settore MED/13 - ENDOCRINOLOGIA, Retrospective cohort study, General Medicine, Middle Aged, Prognosis, medicine.disease, mortality, Confidence interval, Standardized mortality ratio, Italy, epidemiology, Female, Morbidity, business, Follow-Up Studies, Human
Abstract

ObjectiveTo describe demographic and hormonal characteristics, comorbidities (diabetes mellitus and hypertension), therapeutic procedures and their effectiveness, as well as predictors of morbidity and mortality in a nationwide survey of Italian acromegalic patients.DesignRetrospective multicenter epidemiological study endorsed by the Italian Society of Endocrinology and performed in 24 tertiary referral Italian centers. The mean follow-up time was 120 months.ResultsA total of 1512 patients, 41% male, mean age: 45±13 years, mean GH: 31±37 μg/l, IGF1: 744±318 ng/ml, were included. Diabetes mellitus was reported in 16% of cases and hypertension in 33%. Older age and higher IGF1 levels at diagnosis were significant predictors of diabetes and hypertension. At the last follow-up, 65% of patients had a controlled disease, of whom 55% were off medical therapy. Observed deaths were 61, with a standardized mortality ratio of 1.13 95% (confidence interval (CI): 0.87–1.46). Mortality was significantly higher in the patients with persistently active disease (1.93; 95% CI: 1.34–2.70). Main causes of death were vascular diseases and malignancies with similar prevalence. A multivariate analysis showed that older age, higher GH at the last follow-up, higher IGF1 levels at diagnosis, malignancy, and radiotherapy were independent predictors of mortality.ConclusionsPretreatment IGF1 levels are important predictors of morbidity and mortality in acromegaly. The full hormonal control of the disease, nowadays reached in the majority of patients with modern management, reduces greatly the disease-related mortality.

Published
2012

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