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29 results on '"Albertelli M."'

1. Clinical and Metabolic Characterization of Adults With Type 2 Diabetes by Age in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) Cohort

Author

Aroda, Vanita R., Krause-Steinrauf, Heidi, Kazemi, Erin J., Buse, John B., Gulanski, Barbara I., Florez, Hermes J., Ahmann, Andrew J., Loveland, Amy, Kuhn, Alexander, Lonier, Jacqueline Y., Wexler, Deborah J., Crandall, J.P., McKee, M.D., Behringer-Massera, S., Brown-Friday, J., Xhori, E., Ballentine-Cargill, K., Duran, S., Estrella, H., Gonzalez de la torre, S., Lukin, J., Phillips, L.S., Burgess, E., Olson, D., Rhee, M., Wilson, P., Raines, T.S., Boers, J., Costello, J., Maher-Albertelli, M., Mungara, R., Savoye, L., White, C.A., Gullett, C., Holloway, L., Morehead, F., Person, S., Sibymon, M., Tanukonda, S., Adams, C., Ross, A., Balasubramanyam, A., Gaba, R., Gonzalez Hattery, E., Ideozu, A., Jimenez, J., Montes, G., Wright, C., Hollander, P., Roe, E., Jackson, A., Smiley, A., Burt, P., Estrada, L., Chionh, K., Ismail-Beigi, F., Falck-Ytter, C., Sayyed Kassem, L., Sood, A., Tiktin, M., Kulow, T., Newman, C., Stancil, K.A., Cramer, B., Iacoboni, J., Kononets, M.V., Sanders, C., Tucker, L., Werner, A., Maxwell, A., McPhee, G., Patel, C., Colosimo, L., Krol, A., Goland, R., Pring, J., Alfano, L., Kringas, P., Hausheer, C., Tejada, J., Gumpel, K., Kirpitch, A., Schneier, H., Green, J.B., AbouAssi, H., Chatterjee, R., Feinglos, M.N., English Jones, J., Khan, S.A., Kimpel, J.B., Zimmer, R.P., Furst, M., Satterwhite, B.M., Thacker, C.R., Evans Kreider, K., Mariash, C.N., Mather, K.J., Ismail, H.M., Lteif, A., Mullen, M., Hamilton, T., Patel, N., Riera, G., Jackson, M., Pirics, V., Aguillar, D., Howard, D., Hurt, S., Bergenstal, R., Carlson, A., Martens, T., Johnson, M., Hill, R., Hyatt, J., Jensen, C., Madden, M., Martin, D., Willis, H., Konerza, W., Yang, S., Kleeberger, K., Passi, R., Fortmann, S., Herson, M., Mularski, K., Glauber, H., Prihoda, J., Ash, B., Carlson, C., Ramey, P.A., Schield, E., Torgrimson-Ojerio, B., Arnold, K., Kauffman, B., Panos, E., Sahnow, S., Bays, K., Berame, K., Cook, J., Ghioni, D., Gluth, J., Schell, K., Criscola, J., Friason, C., Jones, S., Nazarov, S., Barzilay, J., Rassouli, N., Puttnam, R., Ojoawo, B., Nelson, R., Curtis, M., Hollis, B., Sanders-Jones, C., Stokes, K., El-Haqq, Z., Kolli, A., Tran, T., Wexler, D., Larkin, M., Meigs, J., Chambers, B., Dushkin, A., Rocchio, G., Yepes, M., Steiner, B., Dulin, H., Cayford, M., Chu, K., DeManbey, A., Hillard, M., Martin, K., Thangthaeng, N., Gurry, L., Kochis, R., Raymond, E., Ripley, V., Stevens, C., Park, J., Aroda, V., Ghazi, A., Magee, M., Ressing, Ann, Loveland, A., Hamm, M., Hurtado, M., Kuhn, A., Leger, J., Manandhar, L., Sanchez, O., Young, T., Mofor, F., Garg, R., Lagari-Libhaber, V., Florez, H.J., Valencia, W.M., Marks, J., Casula, S., Oropesa-Gonzalez, L., Hue, L., Cuadot, A., Nieto-Martinez, R., Riccio Veliz, A.K., Gutt, M., Kendal, Y.J., Veciana, B., Ahmann, A., Aby-Daniel, D., Joarder, F., Morimoto, V., Sprague, C., Yamashita, D., Cady, N., Rivera-Eschright, N., Kirchhoff, P., Morales Gomez, B., Adducci, J., Goncharova, A., Hox, S.H., Petrovitch, H., Matwichyna, M., Jenkins, V., Broadwater, L., Ishii, R.R., Bermudez, N.O., Hsia, D.S., Cefalu, W.T., Greenway, F.L., Waguespack, C., King, E., Fry, G., Dragg, A., Gildersleeve, B., Arceneaux, J., Haynes, N., Thomassie, A., Pavlionis, M., Bourgeois, B., Hazlett, C., Mudaliar, S., Henry, R., Boeder, S., Pettus, J., Diaz, E., Garcia-Acosta, D., Maggs, S., DeLue, C., Stallings, A., Castro, E., Hernandez, S., Krakoff, J., Curtis, J.M., Killean, T., Khalid, M., Joshevama, E., Tsingine, K., Karshner, T., Albu, J., Pi-Sunyer, F.X., Frances, S., Maggio, C., Ellis, E., Bastawrose, J., Gong, X., Banerji, M.A., August, P., Lee, M., Lorber, D., Brown, N.M., Josephson, D.H., Thomas, L.L., Tsovian, M., Cherian, A., Jacobson, M.H., Mishko, M.M., Kirkman, M.S., Buse, J.B., Dostou, J., Machineni, S., Young, L., Bergamo, K., Goley, A., Kerr, J., Largay, J.F., Guarda, S., Cuffee, J., Culmer, D., Fraser, R., Almeida, H., Coffer, S., Debnam, E., Kiker, L., Morton, S., Josey, K., Fuller, G., Garvey, W.T., Cherrington, A.L., Dyer, D., Lawson, M.C.R., Griffith, O., Agne, A., McCullars, S., Cohen, R.M., Craig, J., Rogge, M.C., Burton, K., Kersey, K., Wilson, C., Lipp, S., Vonder Meulen, M.B., Adkins, C., Onadeko, T., Rasouli, N., Baker, C., Schroeder, E., Razzaghi, M., Lyon, C., Penaloza, R., Underkofler, C., Lorch, R., Douglass, S., Steiner, S., Sivitz, W.I., Cline, E., Knosp, L.K., McConnell, J., Lowe, T., Herman, W.H., Pop-Busui, R., Tan, M.H., Martin, C., Waltje, A., Katona, A., Goodhall, L., Eggleston, R., Kuo, S., Bojescu, S., Bule, S., Kessler, N., LaSalle, E., Whitley, K., Seaquist, E.R., Bantle, A., Harindhanavudhi, T., Kumar, A., Redmon, B., Bantle, J., Coe, M., Mech, M., Taddese, A., Lesne, L., Smith, S., Desouza, C., Kuechenmeister, L., Shivaswamy, V., Burbach, S., Rodriguez, M.G., Seipel, K., Alfred, A., Morales, A.L., Eggert, J., Lord, G., Taylor, W., Tillson, R., Schade, D.S., Adolphe, A., Burge, M., Duran-Valdez, E., Martinez, J., Bancroft, A., Kunkel, S., Ali Jamaleddin Ahmad, F., Hernandez McGinnis, D., Pucchetti, B., Scripsick, E., Zamorano, A., DeFronzo, R.A., Cersosimo, E., Abdul-Ghani, M., Triplitt, C., Juarez, D., Garza, R.I., Verastiqui, H., Wright, K., Puckett, C., Raskin, P., Rhee, C., Abraham, S., Jordan, L.F., Sao, S., Morton, L., Smith, O., Osornio Walker, L., Schnurr-Breen, L., Ayala, R., Kreymer, R.B., Sturgess, D., Utzschneider, K.M., Kahn, S.E., Alarcon-Casas, L., Wright, L., Boyko, E.J., Tsai, E.C., Trence, D.L., Trikudanathan, S., Fattaleh, B.N., Montgomery, B.K., Atkinson, K.M., Kozedub, A., Concepcion, T., Moak, C., Prikhodko, N., Rhothisen, S., Elasy, T.A., Martin, S., Shackelford, L., Goidel, R., Hinkle, N., Lovell, C., Myers, J., Lipps Hogan, J., McGill, J.B., Salam, M., Schweiger, T., Kissel, S., Recklein, C., Clifton, M.J., Tamborlane, W., Camp, A., Gulanski, B., Inzucchi, S.E., Pham, K., Alguard, M., Gatcomb, P., Lessard, K., Perez, M., Iannone, L., Magenheimer, E., Montosa, A., Burch, H.B., Bremer, A.A., Fradkin, J., Nathan, D.M., Lachin, J.M., Krause-Steinrauf, H., Younes, N., Backman, M., Bebu, I., Butera, N., Buys, C.J., Fagan Murphy, A., Gao, Y., Ghosh, A., Gramzinski, M.R., Kazemi, E., Hall, S.D., Legowski, E., Suratt, C., Tripputi, M., Arey, A., Bethepu, J., Lund, C., Mangat Dhaliwal, P., McGee, P., Mesimer, E., Ngo, L., Steffes, M., Seegmiller, J., Saenger, A., Arends, V., Gabrielson, D., Conner, T., Warren, S., Day, J., Huminik, J., Scrymgeour, A., Soliman, E.Z., Pokharel, Y., Zhang, Z.M., Campbell, C., Hu, J., Keasler, L., Hensley, S., Li, Y., Mihalcea, R., Min, D.J., Perez-Rosas, V., Prosser, L., Resnicow, K., Ye, W., Shao, H., Zhang, P., Luchsinger, J., Sanchez, D., Assuras, S., Groessl, E., Sakha, F., Chong, H., Hillery, N., Everett, B.M., Abdouch, I., Bahtiyar, G., Brantley, P., Broyles, F.E., Canaris, G., Copeland, P., Craine, J.J., Fein, W.L., Gliwa, A., Hope, L., Lee, M.S., Meiners, R., Meiners, V., O’Neal, H., Park, J.E., Sacerdote, A., Sledge, E., Soni, L., Steppel-Reznik, J., Turchin, A., Brooks-Worrell, B., Hampe, C.S., Newgard, C.B., Palmer, J.P., Shojaie, A., Higgins, J., Fischer, L., Golden, S., Gonzalez, J., Naik, A., Walker, E., Doner Lotenberg, L., Gallivan, J.M., Lim, J., and Tuncer, D.M.

Subjects
Clinical Care/Education/Nutrition/Psychosocial Research
Abstract

OBJECTIVE: Differences in type 2 diabetes phenotype by age are described, but it is not known whether these differences are seen in a more uniformly defined adult population at a common early stage of care. We sought to characterize age-related clinical and metabolic characteristics of adults with type 2 diabetes on metformin monotherapy, prior to treatment intensification. RESEARCH DESIGN AND METHODS: In the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE), participants were enrolled who had type 2 diabetes duration

Published
2022

2. Epidemiology of pancreatic neuroendocrine neoplasms. a gender perspective

Author

Muscogiuri, G., Altieri, B., Albertelli, M., Dotto, A., Modica, R., Barrea, L., Fanciulli, G., Feola, T., Baldelli, R., Ruggeri, R. M., Gallo, M., Guarnotta, V., Malandrino, P., Messina, E., Venneri, M. A., Giannetta, E., Ferone, D., Colao, A., Faggiano, A., Bottiglieri, F., Campione, S., de Cicco, F., Dicitore, A., Ferrau, F., Grillo, F., Grossrubatscher, E., Guadagno, E., Isidori, A. M., Lania, A., Lenzi, A., Calzo, F. L., Pes, L., Pizza, G., Pofi, R., Puliani, G., Rainone, C., Razzore, P., Rizza, L., Rubino, M., Sbardella, E., Sesti, F., Vitale, G., Zatelli, M. C., Muscogiuri G, Altieri B, Albertelli M, Dotto A, Modica R, Barrea L, Fanciulli G, Feola T, Baldelli R, Ruggeri RM, Gallo M, Guarnotta V, Malandrino P, Messina E, Venneri MA, Giannetta E, Ferone D, Colao A, Faggiano A, Muscogiuri, G., Altieri, B., Albertelli, M., Dotto, A., Modica, R., Barrea, L., Fanciulli, G., Feola, T., Baldelli, R., Ruggeri, R. M., Gallo, M., Guarnotta, V., Malandrino, P., Messina, E., Venneri, M. A., Giannetta, E., Ferone, D., Colao, A., Faggiano, A., Bottiglieri, F., Campione, S., de Cicco, F., Dicitore, A., Ferrau, F., Grillo, F., Grossrubatscher, E., Guadagno, E., Isidori, A. M., Lania, A., Lenzi, A., Calzo, F. L., Pes, L., Pizza, G., Pofi, R., Puliani, G., Rainone, C., Razzore, P., Rizza, L., Rubino, M., Sbardella, E., Sesti, F., Vitale, G., and Zatelli, M. C.

Subjects
Male, medicine.medical_specialty, Cardiovascular diseases, Epidemiology, Gender, Pancreatic neuroendocrine neoplasms, Sex, Type 2 diabetes, Female, Humans, Middle Aged, Pancreas, Retrospective Studies, Diabetes Mellitus, Type 2, Neuroendocrine Tumors, Pancreatic Neoplasms, Pancreatic neuroendocrine neoplasm, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Disease, Neuroendocrine tumors, Type 2 diabete, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Retrospective Studie, Internal medicine, Diabetes mellitus, medicine, gender, Pancrea, sex, business.industry, pancreatic neuroendocrine neoplasms, Retrospective cohort study, medicine.disease, Cardiovascular disease, cardiovascular diseases, Natural history, 030220 oncology & carcinogenesis, Pancreatitis, epidemiology, type 2 diabetes, business, Neuroendocrine Tumor, Human
Abstract

Purpose: Pancreatic neuroendocrine neoplasms (PNENs) are a group of clinically rare and heterogeneous tumors of the pancreas. Currently there are no studies investigating the gender difference in PNEN susceptibility. Thus, the purpose of this study was aimed at examining how gender shapes risk factors, clinicopathological features, and comorbidities in PNENs. Methods: The study design consisted of an Italian multicenter, retrospective study. The study included all consecutive patients with PNENs followed at the participating centers. Two hundred and twenty-nine patients (105 males,124 females, age 54 ± 0.98 years) with PNENs were enrolled at the participating centers. The clinicopathological features (age, gender, BMI, histology, tumor size, tumor grade, distant metastasis, hormonal function, and diagnostic circumstances), comorbidities (cardiovascular diseases (CVD), pancreatitis, type 2 diabetes (T2DM), and potential risk factors (smoking and drinking) were included in the analysis. Results: Females were slightly prevalent (54.15%). PNENs were diagnosed at younger age in females compared to males (p = 0.04). The prevalence of CVD was significantly higher in males than in females (p = 0.006). In the female group, the presence of T2DM was significantly associated with higher tumor grade (p = 0.04) and metastatic disease (p = 0.02). The proportion of smokers and alcohol drinkers was significantly higher in the male group (p < 0.001). No significant gender differences were detected regarding the other parameters included in the analysis. Conclusions: This study has identified gender differences of PNENs in terms of age at diagnosis, associated comorbidities, and potential risk factors. A gender-tailored approach could become a potential strategy to better understand the natural history of PNENs and improve the effectiveness of PNENs clinical management.

Published
2020

3. Open issues on G3 neuroendocrine neoplasms: back to the future

Author

Zatelli, Maria Chiara, Guadagno, Elia, Messina, Erika, Lo Calzo, Fabio, Faggiano, Antongiulio, Colao, Annamaria, Albertelli, M., Bianchi, A., CIRCELLI, MARIA TERESA, De Cicco, F., Dicitore, A., Di Dato, C., MOLFETTA, MARIA TERESA, Fanciulli, G., Ferraù, F., Gallo, M., GIANNETTA, MASSIMO, Grillo, F., Grossrubatscher, E., Guarnotta, V., Isidori, A. M., Kara, E., MALANDRINO, CORRADO, Modica, R., Muscogiuri, G., Pizza, G., Razzore, P., Rota, F., Rubino, M., Ruggeri, R. M., Sciammarella, C., Vitale, G., Zatelli, Maria Chiara, Guadagno, Elia, Messina, Erika, Lo Calzo, Fabio, Faggiano, Antongiulio, Colao, Annamaria, Albertelli, M., Bianchi, A., Circelli, MARIA TERESA, De Cicco, F., Dicitore, A., Di Dato, C., Molfetta, MARIA TERESA, Fanciulli, G., Ferraù, F., Gallo, M., Giannetta, Massimo, Grillo, F., Grossrubatscher, E., Guarnotta, V., Isidori, A. M., Kara, E., Malandrino, Corrado, Modica, R., Muscogiuri, G., Pizza, G., Razzore, P., Rota, F., Rubino, M., Ruggeri, R. M., Sciammarella, C., and Vitale, G.

Subjects
0301 basic medicine, Cancer Research, medicine.medical_specialty, Prognosi, Endocrinology, Diabetes and Metabolism, Neuroendocrine tumors, Diagnosis, G3, neuroendocrine tumors, prognosis, endocrinology, diabetes and metabolism, oncology, cancer research, NO, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Neuroendocrine tumor, medicine, Humans, Prognosis, Oncology, Intensive care medicine, business.industry, medicine.disease, Neuroendocrine Carcinomas, Diabetes and Metabolism, 030104 developmental biology, 030220 oncology & carcinogenesis, Neoplasm Grading, business, Diagnosi
Abstract

The recent recognition that grade 3 (G3) neuroendocrine neoplasms (NENs) can be divided into two different categories according to the histopathological differentiation, that is G3 neuroendocrine tumors (NETs) and G3 neuroendocrine carcinomas (NECs) has generated a lot of interest concerning not only the diagnosis, but also the differential management of such new group of NENs. However, several issues need to be fully clarified in order to put G3 NETs and G3 NECs in the right place. The aim of this review is to focus on those issues that are still undetermined starting from the current knowledge, evaluating the available evidence and the possible clinical implications.

Published
2018
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4. Emerging Therapies in Pheochromocytoma and Paraganglioma: Immune Checkpoint Inhibitors in the Starting Blocks

Author

Fanciulli G., Di Molfetta S., Dotto A., Florio T., Feola T., Rubino M., de Cicco F., Colao A., Faggiano A., Albertelli M., Altieri B., Barrea L., Bottiglieri F., Campione S., Dicitore A., Ferone D., Ferrau F., Grossrubatscher E., Gallo M., Giannetta E., Grillo F., Guadagno E., Guarnotta V., Isidori A. M., Lania A., Lenzi A., Lo Calzo F., Malandrino P., Messina E., Modica R., Muscogiuri G., Pizza G., Pes L., Pofi R., Puliani G., Rainone C., Razzore P., Rizza L., Ruggieri R. M., Sbardella E., Sesti F., Venneri M. A., Vitale G., Zatelli M. C., Fanciulli G., Di Molfetta S., Dotto A., Florio T., Feola T., Rubino M., de Cicco F., Colao A., Faggiano A., Albertelli M., Altieri B., Barrea L., Bottiglieri F., Campione S., Dicitore A., Ferone D., Ferrau F., Grossrubatscher E., Gallo M., Giannetta E., Grillo F., Guadagno E., Guarnotta V., Isidori A.M., Lania A., Lenzi A., Lo Calzo F., Malandrino P., Messina E., Modica R., Muscogiuri G., Pizza G., Pes L., Pofi R., Puliani G., Rainone C., Razzore P., Rizza L., Ruggieri R.M., Sbardella E., Sesti F., Venneri M.A., Vitale G., Zatelli M.C., Fanciulli, G., Di Molfetta, S., Dotto, A., Florio, T., Feola, T., Rubino, M., de Cicco, F., Colao, A., Faggiano, A., Albertelli, M., Altieri, B., Barrea, L., Bottiglieri, F., Campione, S., Dicitore, A., Ferone, D., Ferrau, F., Grossrubatscher, E., Gallo, M., Giannetta, E., Grillo, F., Guadagno, E., Guarnotta, V., Isidori, A. M., Lania, A., Lenzi, A., Lo Calzo, F., Malandrino, P., Messina, E., Modica, R., Muscogiuri, G., Pizza, G., Pes, L., Pofi, R., Puliani, G., Rainone, C., Razzore, P., Rizza, L., Ruggieri, R. M., Sbardella, E., Sesti, F., Venneri, M. A., Vitale, G., and Zatelli, M. C.

Subjects
atezolizumab, avelumab, cemiplimab, durvalumab, immune checkpoint inhibitors, ipilimumab, nivolumab, paraganglioma, pembrolizumab, pheochromocytoma, lcsh:Medicine, Ipilimumab, Review, Immune checkpoint inhibitor, Pembrolizumab, Bioinformatics, Pheochromocytoma, Avelumab, 03 medical and health sciences, 0302 clinical medicine, Paraganglioma, Atezolizumab, Medicine, Ate-zolizumab, 030304 developmental biology, 0303 health sciences, business.industry, lcsh:R, General Medicine, medicine.disease, Clinical trial, 030220 oncology & carcinogenesis, Nivolumab, business, medicine.drug
Abstract

Pheochromocytoma and paraganglioma are neuroendocrine neoplasms, originating in the adrenal medulla and in parasympathetic and sympathetic autonomic nervous system ganglia, respectively. They usually present as localized tumours curable with surgery. However, these tumours may exhibit heterogeneous clinical course, ranging from no/minimal progression to aggressive (progressive/metastatic) behavior. For this setting of patients, current therapies are unsatisfactory. Immune checkpoint inhibitors have shown outstanding results for several types of solid cancers. We therefore aimed to summarize and discuss available data on efficacy and safety of current FDA-approved immune checkpoint inhibitors in patients with pheochromocytoma and paraganglioma. After an extensive search, we found 15 useful data sources (four full-published articles, four supplements of scientific journals, seven ongoing registered clinical trials). The data we detected, even with the limit of the small number of patients treated, make a great expectation on the therapeutic use of immune checkpoint inhibitors. Besides, the newly detected predictors of response will (hopefully) be of great helps in selecting the subset of patients that might benefit the most from this class of drugs. Finally, new trials are in the starting blocks, and they are expected to shed in the next future new light on a therapy, which is considered a milestone in oncology.

Published
2020
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5. Expected and paradoxical effects of obesity on cancer treatment response

Author

Gallo, M, Adinolfi, V, Barucca, V, Prinzi, N, Renzelli, V, Barrea, L, Di Giacinto, P, Ruggeri, Rm, Sesti, F, Arvat, E, Baldelli, R, Eolo, Group, Colao, A, Isidori, A, Lenzi, A, Baldell, R, Albertelli, M, Attala, D, Bianchi, A, Di Sarno, A, Feola, T, Mazziotti, G, Nervo, A, Pozza, C, Puliani, G, Razzore, P, Ramponi, S, Ricciardi, S, Rizza, L, Rota, F, Sbardella, E, and Zatelli, Mc.

Subjects
Oncology, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, body mass index, cancer, cancer therapy, obesity, overweight, treatment outcome, Overweight, NO, Body Mass Index, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Risk Factors, Internal medicine, Diabetes mellitus, Neoplasms, Epidemiology, medicine, Humans, Cancer, Obesity, Body mass index, Cancer therapy, Treatment outcome, LS4_3, Risk factor, business.industry, medicine.disease, Prognosis, Cardiovascular Diseases, medicine.symptom, business, Obesity paradox
Abstract

Obesity, whose prevalence is pandemic and continuing to increase, is a major preventable and modifiable risk factor for diabetes and cardiovascular diseases, as well as for cancer. Furthermore, epidemiological studies have shown that obesity is a negative independent prognostic factor for several oncological outcomes, including overall and cancer-specific survival, for several site-specific cancers as well as for all cancers combined. Yet, a recently growing body of evidence suggests that sometimes overweight and obesity may associate with better outcomes, and that immunotherapy may show improved response among obese patients compared with patients with a normal weight. The so-called 'obesity paradox' has been reported in several advanced cancer as well as in other diseases, albeit the mechanisms behind this unexpected relationship are still not clear. Aim of this review is to explore the expected as well as the paradoxical relationship between obesity and cancer prognosis, with a particular emphasis on the effects of cancer therapies in obese people.

Published
2020

6. Immune checkpoint blockade for Merkel cell carcinoma: actual findings and unanswered questions

Author

Gallo M., Guarnotta V., De Cicco F., Rubino M., Faggiano A., Colao A., Albertelli M., Altieri B., Ambrosetti E., Bianchi A., Bottiglieri L., Campione S., Carra S., Di Dato C., DiMolfetta S., Di Sarno A., Fanciulli G., Ferone D., Ferrau F., Giannetta E., Grillo F., Grossrubatscher E. M., Guadagno E., Isidori A., Lo Calzo F., Malandrino P., Martini C., Messina E., Modica R., Muscogiuri G., Pizza G., Razzore P., Rizza L., Ruggeri R. M., Sciammarella C., Vitale G., Zatelli M. C., Gallo, M., Guarnotta, V., De Cicco, F., Rubino, M., Faggiano, A., Colao, A., Albertelli, M., Altieri, B., Ambrosetti, E., Bianchi, A., Bottiglieri, L., Campione, S., Carra, S., Di Dato, C., Dimolfetta, S., Di Sarno, A., Fanciulli, G., Ferone, D., Ferrau, F., Giannetta, E., Grillo, F., Grossrubatscher, E. M., Guadagno, E., Isidori, A., Lo Calzo, F., Malandrino, P., Martini, C., Messina, E., Modica, R., Muscogiuri, G., Pizza, G., Razzore, P., Rizza, L., Ruggeri, R. M., Sciammarella, C., Vitale, G., Zatelli, M. C., and Gallo Marco, Guarnotta Valentina, De Cicco Federica, Rubino Manila, Faggiano Antongiulio, Colao Annamaria

Subjects
0301 basic medicine, Cancer Research, medicine.medical_specialty, Avelumab, Skin Neoplasms, Prognosi, medicine.medical_treatment, Pembrolizumab, Immune checkpoint inhibitor, Cochrane Library, B7-H1 Antigen, Settore MED/13 - Endocrinologia, 03 medical and health sciences, Immune checkpoint inhibitors, 0302 clinical medicine, Merkel cell carcinoma, Neuroendocrine tumours, Neuroendocrine tumour, medicine, Animals, Humans, Skin Neoplasm, Intensive care medicine, business.industry, Animal, Antibodies, Monoclonal, General Medicine, Immunotherapy, medicine.disease, Prognosis, Immune checkpoint, Blockade, Clinical trial, Carcinoma, Merkel Cell, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Therapy, business, medicine.drug, Human
Abstract

Purpose: Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine carcinoma arising from the skin. We aimed to review and deal with some of the most relevant controversial topics on the correct use of immunotherapy for the treatment of MCC. Methods: The primary search was carried out via PubMed, EMBASE, and the Cochrane Library (until 31st May, 2018), while other articles and guidelines were retrieved from related papers or those referenced in these papers. Additionally, we performed an extensive search on ClinicalTrials.gov to gather information on the ongoing clinical trials related to this specific topic. Results: We performed an up-to-date critical review taking into account the results of both retrospective and prospective published studies evaluating these issues: Are there any predictive criteria of response to immunotherapy? What is the correct place of immunotherapy in the treatment algorithm of MCC? What is the best choice after immunotherapy failure? What to do with patients for whom immunotherapy is not been feasible or contraindicated? How long should immunotherapy be prolonged, and what follow-up should be offered after complete response? Conclusion: The therapeutic landscape of MCC is rapidly evolving: many open issues will probably be resolved, and many other questions are likely to arise in the next few years. The results of ongoing prospective clinical trials and of several other studies on these issues are eagerly awaited.

Published
2019

7. A rare rarity: neuroendocrine tumor of the esophagus

Author

Giannetta, Elisa, Guarnotta, Valentina, Rota, Francesca, de Cicco, Federica, Grillo, Federica, Colao, Annamaria, Faggiano, Antongiulio, Albertelli, M., Bianchi, A., Circelli, L., Dicitore, A., Di Dato, C., Di Molfetta, S., Fanciulli, G., Ferrau, F., Gallo, M., Grossrubatscher, E., Guadagno, E., Lo Calzo, F., Kara, E., Malandrino, P., Messina, E., Modica, R., Muscogiuri, G., Pizza, G., Razzore, P., Rubino, M., Ruggeri, R. M., Sciammarella, C., Vitale, G., Zatelli, M. C., Giannetta, Elisa, Guarnotta, Valentina, Rota, Francesca, de Cicco, Federica, Grillo, Federica, Colao, Annamaria, Faggiano, Antongiulio, Albertelli, M., Bianchi, A., Circelli, L., Dicitore, A., Di Dato, C., Di Molfetta, S., Fanciulli, G., Ferrau, F., Gallo, M., Grossrubatscher, E., Guadagno, E., Lo Calzo, F., Kara, E., Malandrino, P., Messina, E., Modica, R., Muscogiuri, G., Pizza, G., Razzore, P., Rubino, M., Ruggeri, R. M., Sciammarella, C., Vitale, G., and Zatelli, M. C.

Subjects
0301 basic medicine, medicine.medical_specialty, Carcinoid tumors, esophageal neoplasms, Neuroendocrine tumors, Small-cell carcinoma, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, gastroenteropancreatic NET, Internal medicine, Epidemiology, medicine, risk factors, esophageal NEC, large cell esophageal NEN, MANEC, small cell carcinoma, delayed diagnosis, humans, neuroendocrine tumors, prognosis, rare diseases, Esophagus, Stage (cooking), business.industry, Large cell, Hematology, medicine.disease, Dysphagia, 030104 developmental biology, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, medicine.symptom, business
Abstract

Esophageal Neuroendocrine tumors (NETs) are rare, aggressive and lacking specific symptoms. This causes a diagnostic delay, worsening the prognosis. Numerous cases are reported in literature, without a consensus on the management. Our aim was to clarify epidemiology, clinical presentation, diagnostic, therapeutic management of esophageal NETs. Extensive literature search identified a total of 226 articles. One hundred twenty-five articles (n = 1676) met the inclusion criteria, showing that: the incidence of esophageal NET varies geographically; men (60–70 years) are more affected; smoking and alcohol abuse are the major risk factors; dysphagia, weight loss, appetite loss are the most common clinical features. The histotypes include high-grade small and large cell esophageal carcinomas and low-grade carcinoid tumors. Mixed neuroendocrine/non-neuroendocrine neoplasms are the most common. Often the diagnosis occurs randomly on endoscopic examination. Circulating markers, functional combined with conventional imaging contributes to the diagnosis and management. Treatment depends on type, grade and stage of the tumor.

Published
2019

8. Second primary neoplasms in patients with lung and gastroenteropancreatic neuroendocrine neoplasms: Data from a retrospective multi-centric study

Author

Massironi, S., Campana, D., Pusceddu c, S., Albertelli, M., Faggiano e, A., Panzuto f, F., Smiroldo g, V., Andreasi h, V., Rossi i, R. E., Maggio b, I., Torchio c, M., Dotto, A., Modica j, R., Rinzivillo f, M., Carnaghi k, C., Partelli h, S., Fanetti l, I., Lamberti b, G., Corti c, F., Ferone, D., Colao j, A., Annibale f, B., M, Invernizzi a, P., Falconi h, M., and ItaNet (Italian Association for Neuroendocrine Tumours) Study Group

Published
2020

9. GOSAFE - Geriatric Oncology Surgical Assessment and Functional rEcovery after Surgery: early analysis on 977 patients

Author

Montroni, I, Rostoft, S, Spinelli, A, Van Leeuwen, BL, Ercolani, G, Saur, NM, Jaklitsch, MT, Somasundar, PS, Carino, ND, Ghignone, F, Foca, F, Zingaretti, C, Audisio, RA, Ugolini, G, Garutti, A, Taffurelli, G, Zattoni, D, Tramelli, P, Sermonesi, G, Di Candido, F, Carvello, M, Sacchi, M, De Lucia, F, Foppa, C, Plas, M, Van der Wal-Huisman, H, Tauceri, F, Perenze, B, Di Pietrantonio, D, Mirarchi, M, Fejka, M, Bleier, JIS, Frain, L, Fox, SW, Cardin, K, De Leon, LE, Baltatzis, M, Chan, AKC, Siriwardena, AK, Vertogen, B, Nanni, O, Garulli, G, Alagna, V, Pirrera, B, Lucchi, A, Monari, F, Conti, L, Capelli, P, Romboli, A, Palmieri, G, Banchini, F, Marano, L, Spaziani, A, Castagnoli, G, Bartoli, A, Trompetto, M, Gallo, G, Luc, AR, Clerico, G, Sammarco, G, De Luca, R, Barile, G, Simone, M, Costanzi, A, Mari, G, Maggioni, D, Pellegrino, R, Riggio, V, Kenig, J, Szabat, K, Scabini, S, Pertile, D, Stratta, E, Massobrio, A, Soriero, D, Nesbakken, A, Lonn, M, Backe, IF, Ferrari, G, Mazzola, M, Alampi, BDA, Achilli, P, Sfondrini, S, Ioannidis, O, Loutzidou, L, Galanos-Demiris, K, Pellino, G, Balducci, G, Frezza, B, Lucarini, A, Santos, C, Cooper, L, Siam, B, Levy, Y, Brenner, B, Kashtan, H, Belgrano, V, De Cian, F, Palermo, B, Eggenhoffner, R, Albertelli, M, Sanchez-Guillen, L, Arroyo, A, Lopez-Rodriguez, F, Lario, S, Lillo, C, Wexner, SD, SIOG Surgical Task Force, and ESSO GOSAFE Study Grp

Subjects
MULTICENTER, CANCER
Abstract

Objective: Older patients with cancer value functional outcomes as much as survival, but surgical studies lack functional recovery (FR) data. The value of a standardized frailty assessment has been confirmed, yet it's infrequently utilized due to time restrictions into everyday practice. The multicenter GOSAFE study was designed to (1) evaluate the trajectory of patients' quality of life (QoL) after cancer surgery (2) assess baseline frailty indicators in unselected patients (3) clarify the most relevant tools in predicting FR and clinical outcomes. This is a report of the study design and baseline patient evaluations. Materials & Methods: GOSAFE prospectively collected a baseline multidimensional evaluation before major elective surgery in patients (70 years) from 26 international units. Short-/mid-/Iong-term surgical outcomes were recorded with QoL and FR data. Results: 1003 patients were enrolled in a 26-month span. Complete baseline data were available for 977(97.4%). Median age was 78 years (range 70-94); 52.8% males. 968(99%) lived at home, 51.6% without caregiver. 54.4% had 3 medications, 5.9% none. Patients were dependent (ADL < 5) in 7.9% of the cases. Frailty was either detected by G8 = 2(37.4%), TUG > 20 s (5.2%) or ASAIII-IV (48.8%). Major comorbidities (CACI > 6) were detected in 36%; 20.9% of patients had cognitive impairment according to Mini-Cog. Conclusion: The GOSAFE showed that frailty is frequent in older patients undergoing cancer surgery. QoL and FR, for the first time, are going to be primary outcomes of a real-life observational study. The crucial role of frailty assessment is going to be addressed in the ability to predict postoperative outcomes and to correlate with QoL and FR. (C) 2019 Elsevier Ltd. All rights reserved.

Published
2020

10. Predictive factors of response to mTOR inhibitors in neuroendocrine tumours

Author

Zatelli, Maria Chiara, Fanciulli, Giuseppe, Malandrino, Pasqualino, NIKE GROUP: Albertelli M, Arvat E, Baldelli R, Berruti A, Bianchi A, Bodei L, Botti G, Corcione F, Daví MV, Delle Fave G, De Marinis L, Di Sarno A, Dicitore A, Fazio N, Ferolla P, Ferone D, Filice A, Gallo M, Giordano C, Giuffrida D, Guarnotta V, Lania A, Lastoria S, Logoluso F, Loli P, Manzoni M, Marchetti M, Martini C, Messina E, Modica R, Motta C, Papotti M, Partelli S, Persico G, Pia A, Piovesan A, Pontecorvi A, Razzore P, Rota F, Scavuzzo F, Sciammarella C, Vitale G., RAMUNDO, VALERIA, FAGGIANO, ANTONGIULIO, COLAO, ANNAMARIA, DE ROSA, GAETANO, Zatelli, M, Fanciulli, G, Malandrino, P, Ramundo, V, Faggiano, A, Colao, A, Giordano, C, Zatelli, Mc, Nike, Group, Partelli, S, Zatelli, Maria Chiara, Fanciulli, Giuseppe, Malandrino, Pasqualino, Ramundo, Valeria, Faggiano, Antongiulio, Colao, Annamaria, NIKE GROUP: Albertelli, M, Arvat, E, Baldelli, R, Berruti, A, Bianchi, A, Bodei, L, Botti, G, Corcione, F, Daví, Mv, Delle Fave, G, De Marinis, L, DE ROSA, Gaetano, Di Sarno, A, Dicitore, A, Fazio, N, Ferolla, P, Ferone, D, Filice, A, Gallo, M, Giuffrida, D, Guarnotta, V, Lania, A, Lastoria, S, Logoluso, F, Loli, P, Manzoni, M, Marchetti, M, Martini, C, Messina, E, Modica, R, Motta, C, Papotti, M, Persico, G, Pia, A, Piovesan, A, Pontecorvi, A, Razzore, P, Rota, F, Scavuzzo, F, Sciammarella, C, and Vitale, G.

Subjects
0301 basic medicine, Oncology, Cancer Research, mTOR inhibitor, Endocrinology, Diabetes and Metabolism, Neuroendocrine tumors, Antineoplastic Agent, 0302 clinical medicine, Endocrinology, Neuroendocrine tumours, neuroendocrine tumour, Treatment resistance, MTOR inhibitors, Tumor, Medical treatment, TOR Serine-Threonine Kinases, Discovery and development of mTOR inhibitors, Response to treatment, Patient management, Diabetes and Metabolism, Neuroendocrine Tumors, 030220 oncology & carcinogenesis, Neuroendocrine Tumor, Human, Predictors, Animals, Antineoplastic Agents, Biomarkers, Tumor, Diagnostic Imaging, Humans, Protein Kinase Inhibitors, medicine.medical_specialty, Protein Kinase Inhibitor, Early detection, predictor, Biology, NO, 03 medical and health sciences, mTOR inhibitors, neuroendocrine tumours, predictors, response to treatment, Internal medicine, medicine, mTOR inhibitors,neuroendocrine tumours,predictors,response to treatment, mTOR inhibitors, neuroendocrine tumours, predictors, response to treatment, Animal, medicine.disease, 030104 developmental biology, Immunology, Biomarkers, Resource utilization
Abstract

Medical treatment of neuroendocrine tumours (NETs) has drawn a lot of attention due to the recent demonstration of efficacy of several drugs on progression-free survival, including somatostatin analogs, small tyrosine kinase inhibitors and mTOR inhibitors (or rapalogs). The latter are approved as therapeutic agents in advanced pancreatic NETs and have been demonstrated to be effective in different types of NETs, with variable efficacy due to the development of resistance to treatment. Early detection of patients that may benefit from rapalogs treatment is of paramount importance in order to select the better treatment and avoid ineffective and expensive treatments. Predictive markers for therapeutic response are under intensive investigation, aiming at a tailored patient management and more appropriate resource utilization. This review summarizes the available data on the tissue, circulating and imaging markers that are potentially predictive of rapalog efficacy in NETs.

Published
2015
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11. Bone Metastases in Neuroendocrine Neoplasms: From Pathogenesis to Clinical Management

Author

Altieri B., Di Dato C., Martini C., Sciammarella C., DI SARNO, ALFONSO, Colao A., Faggiano A., Albertelli M., AMBROSETTI, ENRICO MARIO, Bianchi A., Bottiglieri F., Campione S., Carra S., De Cicco F., Di Molfetta S., Fanciulli G., Ferone D., Ferrau F., Gallo M., Giannetta E., Grillo F., Maria E. G., Guadagno E., Guarnotta V., Isidori A., Lo Calzo F., Malandrino P., Messina E., Modica R., Muscogiuri G., Pizza G., Razzore P., Rizza L., Rubino M., Ruggeri R. M., Vitale G., Zatelli M. C., Altieri, B., Di Dato, C., Martini, C., Sciammarella, C., DI SARNO, Alfonso, Colao, A., Faggiano, A., Albertelli, M., Ambrosetti, ENRICO MARIO, Bianchi, A., Bottiglieri, F., Campione, S., Carra, S., De Cicco, F., Di Molfetta, S., Fanciulli, G., Ferone, D., Ferrau, F., Gallo, M., Giannetta, E., Grillo, F., Maria, E. G., Guadagno, E., Guarnotta, V., Isidori, A., Lo Calzo, F., Malandrino, P., Messina, E., Modica, R., Muscogiuri, G., Pizza, G., Razzore, P., Rizza, L., Rubino, M., Ruggeri, R. M., Vitale, G., and Zatelli, M. C.

Subjects
Oncology, Cancer Research, medicine.medical_specialty, Prognosi, Skeletal-related event, education, Skeletal related events, 030209 endocrinology & metabolism, Review, lcsh:RC254-282, Pathogenesis, Bone metastases, Bone microenvironment, Denosumab, Epithelial-to-mesenchymal transition, Microrna, Neuroendocrine neoplasms, Prognosis, Skeletal-related events, Treatment, 03 medical and health sciences, 0302 clinical medicine, bone metastases, Quality of life, Internal medicine, medicine, neuroendocrine neoplasms, microRNA, treatment, medicine.diagnostic_test, business.industry, digestive, oral, and skin physiology, denosumab, Retrospective cohort study, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, skeletal-related events, Neuroendocrine neoplasm, Clinical Practice, Bone metastase, stomatognathic diseases, Positron emission tomography, Curative treatment, 030220 oncology & carcinogenesis, epithelial-to-mesenchymal transition, prognosis, business, bone microenvironment, medicine.drug
Abstract

Bone represents a common site of metastases for several solid tumors. However, the ability of neuroendocrine neoplasms (NENs) to localize to bone has always been considered a rare and late event. Thanks to the improvement of therapeutic options, which results in longer survival, and of imaging techniques, particularly after the introduction of positron emission tomography (PET) with gallium peptides, the diagnosis of bone metastases (BMs) in NENs is increasing. The onset of BMs can be associated with severe skeletal complications that impair the patient’s quality of life. Moreover, BMs negatively affect the prognosis of NEN patients, bringing out the lack of curative treatment options for advanced NENs. The current knowledge on BMs in gastro-entero-pancreatic (GEP) and bronchopulmonary (BP) NENs is still scant and is derived from a few retrospective studies and case reports. This review aims to perform a critical analysis of the evidence regarding the role of BMs in GEP- and BP-NENs, focusing on the molecular mechanisms underlining the development of BMs, as well as clinical presentation, diagnosis, and treatment of BMs, in an attempt to provide suggestions that can be used in clinical practice.

Published
2019
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13. Optimization of flow reserve measurement using SPECT technology to evaluate the determinants of coronary microvascular dysfunction in diabetes

Author

Marini C. 1, Bezante G. 2, Gandolfo P. 3, Modonesi E. 2, Morbelli S.D. 3, Depascale A. 4, Rollando D. 2, Maggi D. 4, Albertelli M. 4, Armonino R. 3, Balbi M. 2, Brunelli C. 2, Cordera R. 4, Sambuceti G. 3, and 5

Subjects
Transthoracic contrast echo Doppler, Myocardial perfusion reserve, Type 2 diabetes mellitus, GatedSPECT
Abstract

PURPOSE: The aim of this study was to validate a new method to measure regional myocardial perfusion reserve (MPR) with technetium-labelled tracers in patients with type 2 diabetes mellitus (DM2). METHODS: A total of 40 consecutive DM2 patients without history of coronary artery disease (CAD) and 7 control subjects were recruited. Dipyridamole myocardial blood flow index (MBF) was assessed by measuring first transit counts in the pulmonary artery and myocardial count rate from gated SPECT images using (99m)Tc-labelled tracers. The corresponding MBF index was estimated 2 h later according to the same procedure. Regional myocardial perfusion reserve (MPR) was defined as the ratio between dipyridamole and baseline MBF using a 17-segment left ventricular (LV) model. Coronary flow reserve (CFR) was estimated by transthoracic contrast echo Doppler monitoring of flow velocity in the left anterior descending coronary artery (LAD) during the same session. RESULTS: Estimated MPR was higher in control subjects than in patients (3.36 +/- 0.66 vs 1.91 +/- 0.61, respectively, p < 0.01). In patients, LAD CFR and LAD MPR were 2.01 +/- 0.78 vs 1.93 +/- 0.63, respectively (p = ns). The agreement between the two techniques was documented by their close correlation (r = 0.92, p < 0.001) and confirmed by the Bland-Altman analysis. Reversible perfusion defects occurred in 13 patients (32%) who showed similar MPR values as the remaining 27 (2.10 +/- 0.71 vs 1.83 +/- 0.71, respectively, p = ns). Finally, MPR was closely correlated with age (r = -0.50, p < 0.01) and time elapsed from the diagnosis of DM2 (r = -0.51, p < 0.01). CONCLUSION: LV regional MPR can be accurately estimated with the broadly available single photon technology. Application of this method to DM2 patients documents the presence of a microvascular dysfunction homogeneously distributed throughout the LV walls and most frequently not associated with reversible perfusion defects.

Published
2010

14. Hormone and Receptor Candidates for Target and Biotherapy of Neuroendocrine Tumors

Author

Hofland, Leo, Vandamme, TAL, Albertelli, M, Ferone, D, and Internal Medicine

Subjects
hormones, hormone substitutes, and hormone antagonists
Abstract

Neuroendocrine tumors (NETs) produce various hormones and bioactive substances and are known to express a large variety of peptide hormone receptors. While these hormones and receptors play a role in the pathophysiology of this heterogeneous group of tumors, they also form an important target for treatment and diagnosis. One of the most well-known target receptors in NETs are somatostatin receptors. On the basis of the expression of functional somatostatin receptors on the cell surface of NET cells, somatostatin analogs have already been used for decades to control symptoms related to hormonal overproduction in patients with NETs. Recent placebo-controlled studies have also demonstrated a significant antitumor activity, both in functioning and nonfunctioning NETs. Moreover, other peptide hormone receptors (e. g. receptors for GLP-1, CCK, GRP, secretin and dopamine) can be expressed at a high density in NETs. As such, these classes of receptors may also form potential targets for diagnosis and treatment. Finally, in recent years novel biotherapies targeting several growth factor systems have been introduced in the treatment of patients with NETs and are being explored for their efficacy in this setting, either as monotherapy or in combination treatment. This chapter aims to give an overview on the above topic. (C) 2015 S. Karger AG, Basel

Published
2015

15. Somatostatin and dopamine receptor expression in lung carcinoma cells and effects of chimeric somatostatin-dopamine molecules on cell proliferation. Am

Author

Ferone, D., Arvigo, M., Semino, C., Jaquet, P., Saveanu, Alexandru, Taylor, J.E., Moreau, J.P., Culler, M.D., Albertelli, M., Minuto, F., Barreca, A., Gautron, Conception, Interactions cellulaires neuroendocriniennes (ICN), and Université de la Méditerranée - Aix-Marseille 2-Centre National de la Recherche Scientifique (CNRS)

Published
2005

21. Second primary neoplasms in patients with lung and gastroenteropancreatic neuroendocrine neoplasms: Data from a retrospective multi-centric study

Author

Francesco Panzuto, Roberta Modica, Roberta Elisa Rossi, M. Torchio, Antongiulio Faggiano, Stefano Partelli, Valentina Andreasi, Francesca Corti, C. Carnaghi, I Fanetti, A. Colao, Andrea Dotto, Massimo Falconi, Diego Ferone, Manuela Albertelli, V. Smiroldo, Sara Massironi, Ilaria Maggio, Bruno Annibale, Sara Pusceddu, Davide Campana, Giuseppe Lamberti, Maria Rinzivillo, Pietro Invernizzi, Massironi, S., Campana, D., Pusceddu, S., Albertelli, M., Faggiano, A., Panzuto, F., Smiroldo, V., Andreasi, V., Rossi, R. E., Maggio, I., Torchio, M., Dotto, A., Modica, R., Rinzivillo, M., Carnaghi, C., Partelli, S., Fanetti, I., Lamberti, G., Corti, F., Ferone, D., Colao, A., Annibale, B., Invernizzi, P., Falconi, M., Massironi S., Campana D., Pusceddu S., Albertelli M., Faggiano A., Panzuto F., Smiroldo V., Andreasi V., Rossi R.E., Maggio I., Torchio M., Dotto A., Modica R., Rinzivillo M., Carnaghi C., Partelli S., Fanetti I., Lamberti G., Corti F., Ferone D., Colao A., Annibale B., Invernizzi P., Falconi M., Massironi, S, Campana, D, Pusceddu, S, Albertelli, M, Faggiano, A, Panzuto, F, Smiroldo, V, Andreasi, V, Rossi, R, Maggio, I, Torchio, M, Dotto, A, Modica, R, Rinzivillo, M, Carnaghi, C, Partelli, S, Fanetti, I, Lamberti, G, Corti, F, Ferone, D, Colao, A, Annibale, B, Invernizzi, P, Falconi, M, and Rossi, R E

Subjects
Oncology, Adult, Male, medicine.medical_specialty, Lung Neoplasms, Referral, Population, Malignancy, Prostate, Internal medicine, Medicine, Humans, In patient, education, Second Primary Neoplasms, Gastrointestinal Neoplasms, Aged, Retrospective Studies, Aged, 80 and over, education.field_of_study, Lung, Hepatology, business.industry, Incidence, Second primary malignancy (SPM), Gastroenterology, Retrospective cohort study, Neoplasms, Second Primary, Middle Aged, medicine.disease, Neuroendocrine neoplasms (NEN), Lung Neoplasm, Neuroendocrine Tumors, medicine.anatomical_structure, Gastrointestinal Neoplasm, Female, business, Neuroendocrine Tumor, Second primary neoplasia, Neuroendocrine tumors (NET), Human
Abstract

Background: Patients with sporadic neuroendocrine neoplasms may exhibit a higher risk of a second primary tumor than the general population. Aim: This study aimed to analyze the occurrence of second primary malignancies.Methods: A retrospective cohort of 2757 patients with sporadic lung and gastro-entero-pancreatic neuroendocrine neoplasms, managed at eight Italian tertiary referral Centers, was included.Results: Between 20 0 0 and 2019, a second primary malignancy was observed in 271 (9.8%) neuroendocrine neoplasms patients with 32 developing a third tumor. There were 135 (49.8%) females and the median age was 64 years. The most frequent locations of the second tumors were breast (18.8%), prostate (12.5%), colon (9.6%), blood tumors (8.5%), and lung (7.7%). The second primary tumor was synchronous in 19.2% of cases, metachronous in 43.2%, and previous in 37.6%. As concerned the neuroendocrine neoplasms, the 5and 10-year survival rates were 87.8% and 74.4%, respectively. PFS for patients with a second primary malignancy was shorter than for patients without a second primary malignancy. Death was mainly related to neuroendocrine neoplasms.Conclusion: In NEN patients the prevalence of second primary malignancies was not negligible, suggest ing a possible neoplastic susceptibility. Overall survival was not affected by the occurrence of a second primary malignancy. (C) 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Published
2021

22. From microbiota toward gastro-enteropancreatic neuroendocrine neoplasms: Are we on the highway to hell?

Author

Giulia Puliani, Andrea Lania, Fabio Lo Calzo, Valentina Guarnotta, Giuseppe Fanciulli, Alessandra Dicitore, Carmen Rainone, Annamaria Colao, Genoveffa Pizza, Manila Rubino, Giovanni Vitale, Severo Campione, Francesco Ferraù, Maria Chiara Zatelli, Mary Anna Venneri, Emilia Sbardella, Diego Ferone, Marco Gallo, Riccardo Pofi, Roberta Modica, Luigi Barrea, Erika Grossrubatscher, Federica Grillo, Antongiulio Faggiano, Franz Sesti, Rosa Maria Ruggieri, Barbara Altieri, Erika Messina, Luca Pes, P. Razzore, Nike, Andrea M. Isidori, Sergio Di Molfetta, Pasquale Malandrino, Andrea Lenzi, Manuela Albertelli, Tiziana Feola, Laura Rizza, Giovanna Muscogiuri, Federica de Cicco, Filomena Bottiglieri, Elia Guadagno, Elisa Giannetta, Vitale G, Dicitore A, Barrea L, Sbardella E, Razzore P, Campione S, Faggiano A, Colao A, NIKE, Albertelli M, Altieri B, Bottiglieri F, De Cicco F, Di Molfetta S, Fanciulli G, Feola T, Ferone D, Ferraù F, Gallo M, Giannetta E, Grillo F, Grossrubatscher E, Guadagno E, Guarnotta V, Isidori AM, Lania A, Lenzi A, Calzo FL, Malandrino P, Messina E, Modica R, Muscogiuri G, Pes L, Pizza G, Pofi R, Puliani G, Rainone C, Rizza L, Rubino M, Ruggieri RM, Sesti F, Venneri MA, Zatelli MC., Vitale, G., Dicitore, A., Barrea, L., Sbardella, E., Razzore, P., Campione, S., Faggiano, A., Colao, A., Albertelli, M., Altieri, B., Bottiglieri, F., De Cicco, F., Di Molfetta, S., Fanciulli, G., Feola, T., Ferone, D., Ferrau, F., Gallo, M., Giannetta, E., Grillo, F., Grossrubatscher, E., Guadagno, E., Guarnotta, V., Isidori, A. M., Lania, A., Lenzi, A., Calzo, F. L., Malandrino, P., Messina, E., Modica, R., Muscogiuri, G., Pes, L., Pizza, G., Pofi, R., Puliani, G., Rainone, C., Rizza, L., Rubino, M., Ruggieri, R. M., Sesti, F., Venneri, M. A., and Zatelli, M. C.

Subjects
Endocrinology, Diabetes and Metabolism, Tumor microenvironment, Biology, Gut flora, Neuroendocrine tumors, medicine.disease_cause, digestive system, Article, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Immune system, Neuroendocrine tumor, Gastro, medicine, Humans, Cytokine, 030304 developmental biology, Gastrointestinal Neoplasms, Inflammation, 0303 health sciences, Microbiota, digestive, oral, and skin physiology, medicine.disease, biology.organism_classification, Cytokines, Gastrointestinal Microbiome, 030220 oncology & carcinogenesis, Immunology, Dysbiosis, Carcinogenesis, Drug metabolism
Abstract

Gut microbiota is represented by different microorganisms that colonize the intestinal tract, mostly the large intestine, such as bacteria, fungi, archaea and viruses. The gut microbial balance has a key role in several functions. It modulates the host’s metabolism, maintains the gut barrier integrity, participates in the xenobiotics and drug metabolism, and acts as protection against gastro-intestinal pathogens through the host’s immune system modulation. The impaired gut microbiota, called dysbiosis, may be the result of an imbalance in this equilibrium and is linked with different diseases, including cancer. While most of the studies have focused on the association between microbiota and gastrointestinal adenocarcinomas, very little is known about gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs). In this review, we provide an overview concerning the complex interplay between gut microbiota and GEP NENs, focusing on the potential role in tumorigenesis and progression in these tumors.

Published
2020

23. Nonconventional Doses of Somatostatin Analogs in Patients With Progressing Well-Differentiated Neuroendocrine Tumor

Author

Nicole Brighi, Ferdinando Riccardi, Manuela Albertelli, Diego Ferone, Antongiulio Faggiano, Fabio Gelsomino, Annamaria Colao, Anna La Salvia, Sara Pusceddu, Salvatore Tafuto, Roberta Modica, Francesco Panzuto, Chiara De Divitiis, Maria Pia Brizzi, Martina Torchio, Giovanni Butturini, Giuseppe Lamberti, Alberto Bongiovanni, Giuseppe Badalamenti, Davide Campana, Toni Ibrahim, Sara Massironi, Lamberti G., Faggiano A., Brighi N., Tafuto S., Ibrahim T., Brizzi M.P., Pusceddu S., Albertelli M., Massironi S., Panzuto F., Badalamenti G., Riccardi F., Butturini G., Gelsomino F., De Divitiis C., Modica R., Bongiovanni A., La Salvia A., Torchio M., Colao A., Ferone D., Campana D., Lamberti, G., Faggiano, A., Brighi, N., Tafuto, S., Ibrahim, T., Brizzi, M. P., Pusceddu, S., Albertelli, M., Massironi, S., Panzuto, F., Badalamenti, G., Riccardi, F., Butturini, G., Gelsomino, F., De DIvitiis, C., Modica, R., Bongiovanni, A., La Salvia, A., Torchio, M., Colao, A., Ferone, D., and Campana, D.

Subjects
Male, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Octreotide, Neuroendocrine tumors, Lanreotide, Biochemistry, Gastroenterology, chemistry.chemical_compound, Endocrinology, high dose, 80 and over, Medicine, Prospective Studies, Prospective cohort study, lanreotide, NET, nonconventional doses, octreotide, somatostatin analogs, Adult, Aged, Aged, 80 and over, Female, Follow-Up Studies, Hormones, Humans, Liver Neoplasms, Middle Aged, Neuroendocrine Tumors, Prognosis, Retrospective Studies, Somatostatin, Cell Differentiation, nonconventional dose, Response Evaluation Criteria in Solid Tumors, medicine.drug, medicine.medical_specialty, Internal medicine, Adverse effect, business.industry, Biochemistry (medical), medicine.disease, Clinical trial, chemistry, business, Progressive disease
Abstract

Purpose To evaluate the antiproliferative activity and safety of nonconventional high doses of somatostatin analogs (HD-SSA) in patients with well-differentiated gastroenteropancreatic (GEP) neuroendocrine tumors (NET) with radiological disease progression according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria on a previous treatment. Methods A retrospective analysis of prospectively maintained databases from 13 Italian NET-dedicated centers was performed. Main inclusion criteria were: well-differentiated G1 or G2 GEP-NET, progressive disease on a previous treatment, and subsequent treatment with HD-SSA (either by increased administered dose [dose intensity] or shortened interval between administrations [dose density]). Main endpoints were progression-free survival (PFS) and safety. Results Of 198 patients, 140 matched inclusion criteria and were included in the analysis. Overall, median PFS was 31 months. Use of HD-SSA as second-line treatment was associated with reduced risk for progression or death compared with third- or further-line treatment (HR: 2.12; P = 0.004). There was no difference in PFS between HD-SSA by increased dose density (N = 133; 95%) or intensity (N = 7; 5%). Partial response according to RECIST criteria was observed in 12 patients (8.6%), and stable disease was achieved in 106 (75.7%) patients. Adverse events occurred in 21 patients (15.0%), 2 of whom had grade 3 biliary stone disease. No patients discontinued HD-SSA treatment due to adverse events. Conclusions HD-SSA is an active and safe treatment option in patients with progressive well-differentiated GEP-NET. The high rate of objective responses observed deserves prospective validation in ad hoc clinical trials.

Published
2020

24. Biliary Stone Disease in Patients with Neuroendocrine Tumors Treated with Somatostatin Analogs: A Multicenter Study

Author

Diego Ferone, A. Colao, Bruno Annibale, Roberta Modica, Giuseppe Lamberti, Sara Pusceddu, Nicole Brighi, Francesco Panzuto, Andrea Spallanzani, Manuela Albertelli, Maria Rinzivillo, Antongiulio Faggiano, Fabio Gelsomino, Roberta Elisa Rossi, Sara Massironi, Davide Campana, Natalie Prinzi, Brighi, N., Panzuto, F., Modica, R., Gelsomino, F., Albertelli, M., Pusceddu, S., Massironi, S., Lamberti, G., Rinzivillo, M., Faggiano, A., Spallanzani, A., Ferone, D., Prinzi, N., Rossi, R. E., Annibale, B., Colao, A. M., Campana, D., Brighi N., Panzuto F., Modica R., Gelsomino F., Albertelli M., Pusceddu S., Massironi S., Lamberti G., Rinzivillo M., Faggiano A., Spallanzani A., Ferone D., Prinzi N., Rossi R.E., Annibale B., Colao A.M., and Campana D.

Subjects
Adverse event, Cancer Research, medicine.medical_specialty, medicine.medical_treatment, Population, Gallstones, Neuroendocrine tumors, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Intestinal Neoplasms, medicine, Humans, education, Adverse effect, Retrospective Studies, Prophylactic cholecystectomy, education.field_of_study, business.industry, Hazard ratio, medicine.disease, Ursodeoxycholic acid, Pancreatic Neoplasms, Neuroendocrine neoplasm, Neuroendocrine Tumors, Adverse events, Neuroendocrine neoplasms, Oncology, 030220 oncology & carcinogenesis, Gallstone, 030211 gastroenterology & hepatology, Cholecystectomy, Hepatobiliary, business, Somatostatin, medicine.drug, Abdominal surgery
Abstract

Background Somatostatin analogs (SSAs) are the mainstay of neuroendocrine tumor (NET) treatment. Biliary stone disease is reported as a common side effect of SSAs, with a frequency ranging from 10% to 63%. Studies on SSA-treated patients for acromegaly report an increased incidence of biliary stone disease compared with the general population, whereas data on patients with NETs are few. Guidelines are based on weak evidence, thus resulting in conflicting recommendations. The aim of the study is to evaluate biliary stone disease incidence, complications, and risk factors in a large population of SSA-treated patients with NETs. Materials and methods A retrospective analysis of a prospectively collected database was performed. Patients with a diagnosis of NET in seven dedicated centers from 1995 to 2017 were included at the time of SSA start. Results A total of 754 SSA-treated patients were evaluated. Patients with history of cholecystectomy or with known biliary stone disease were excluded; 478 patients were included. Among them, 118 patients (24.7%) received prophylactic ursodeoxycholic acid (UDCA). During the study period, 129 patients (27.0%) developed biliary stone disease; of them, 36 (27.9%) developed biliary complications. On multivariate analysis, primary gastrointestinal (GI)-NET (hazard ratio [HR] 1.76) and related surgery (HR 1.58) were independent risk factors for biliary stone disease. Conclusion We report a high incidence of biliary stone disease particularly in GI-NET or GI surgery. UDCA prophylaxis does not seem to have a protective role. Our data suggest that all patients with primary GI-NET or undergoing abdominal surgery should be considered for prophylactic cholecystectomy; no conclusion could be drawn on the indication of prophylactic cholecystectomy in patients with primary pancreatic or thoracic NET for whom abdominal surgery is not planned. Implications for practice The results of this study confirm an increased rate of gallstones development and related complications in patients with neuroendocrine tumors (NETs) treated with somatostatin analogs (SSAs). NETs of the gastrointestinal (GI) tract and related surgery are independent risk factors for biliary stone disease development. Therefore, all patients with primary GI-NET or undergoing abdominal surgery should be considered for prophylactic cholecystectomy. Data on other subgroups are not exhaustive, and management also evaluating additional clinical features (life expectancy, surgical and anesthesiological risks) should be considered. Prophylactic treatment with ursodeoxycholic acid does not seem to be a protective factor for SSA-related biliary stone disease.

Published
2020

25. GOSAFE - Geriatric Oncology Surgical Assessment and Functional rEcovery after Surgery: early analysis on 977 patients

Author

Barbara Frezza, Giampaolo Castagnoli, Genoveffa Balducci, Valentina Riggio, G. Ugolini, Antonio Arroyo, Gianluca Garulli, Caterina Foppa, Kristin Cardin, Matthijs Plas, Gaetano Gallo, Francesca De Lucia, Francisco López-Rodríguez, Sandra Lario, Franco De Cian, Flavia Foca, Alberto Realis Luc, Paola Tramelli, Roberta Pellegrino, Giacomo Sermonesi, Stefano Sfondrini, Federico Ghignone, Orestis Ioannidis, Nicole M. Saur, Michael David Fejka, Basilio Pirrera, Bruno Alampi, Siri Rostoft, Sam Fox, Chiara Zingaretti, Ingeborg Flåten Backe, Alessandro Spaziani, Barbara Perenze, Minas Baltatzis, Riccardo A. Audisio, Claudia Santos, Luigi Marano, Mariann Lønn, Stefano Scabini, Andrea Massobrio, Patrizio Capelli, Isacco Montroni, Luis E. De León, Cristina Lillo, Alessio Lucarini, Valerio Belgrano, Antonino Spinelli, Daniela Di Pietrantonio, Nicola de Liguori Carino, Davide Pertile, Luigi Conti, Andrea Romboli, Giuseppe Sammarco, Hanoch Kashtan, Baha Siam, Michael T. Jaklitsch, Arild Nesbakken, Michele De Simone, Oriana Nanni, Filippo Banchini, Ajith K. Siriwardena, Giorgio Ercolani, Pietro Achilli, Davide Zattoni, Bernadette Vertogen, Steven D. Wexner, Laura Frain, Konstantinos Galanos-Demiris, Dario Maggioni, Baruch Brenner, Gerardo Palmieri, Giovanni Taffurelli, Barbara L. van Leeuwen, Manuela Albertelli, Gianluca Pellino, Anthony Chan, Alberto Bartoli, Emanuela Stratta, Mario Trompetto, Anna Garutti, Francesca Tauceri, Michele Mazzola, Beatrice Palermo, G. Clerico, Jakub Kenig, Yochai Levy, Graziana Barile, Vincenzo Alagna, Giulio Mari, Roberto Eggenhöffner, Joshua I. S. Bleier, Giovanni Ferrari, Andrea Costanzi, Michele Carvello, Francesca Di Candido, Francesco Monari, Ponnandai Somasundar, Kinga Szabat, Matteo Sacchi, Luis Sánchez-Guillén, Lydia Loutzidou, Lisa Cooper, Hanneke van der Wal-Huisman, Mariateresa Mirarchi, Domenico Soriero, Raffaele De Luca, Andrea Lucchi, Damage and Repair in Cancer Development and Cancer Treatment (DARE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Montroni I., Rostoft S., Spinelli A., Van Leeuwen B.L., Ercolani G., Saur N.M., Jacklitsh M.T., Somasundar P.S., de Liguori Carino N., Ghignone F., Foca F., Zingaretti C., Audisio R.A., Ugolini G., Garutti A., Taffurelli G., Zattoni D., Tramelli P., Sermonesi G., Di Candido F., Carvello M., Sacchi M., De Lucia F., Foppa C., Plas M., Van der Wal-Huisman H., Tauceri F., Perenze B., Di Pietrantonio D., Mirarchi M., Fejka M., Bleier J.I.S., Frain L., Fox S.W., Cardin K., De Leon L.E., Baltatzis M., Chan A.K.C., Siriwardena A.K., Vertogen B., Nanni O., Garulli G., Alagna V., Pirrera B., Lucchi A., Monari F., Conti L., Capelli P., Romboli A., Palmieri G., Banchini F., Marano L., Spaziani A., Castagnoli G., Bartoli A., Trompetto M., Gallo G., Luc A.R., Clerico G., Sammarco G., De Luca R., Barile G., Simone M., Costanzi A., Mari G., Maggioni M., Pellegrino R., Riggio V., Kenig J., Szabat K., Scabini S., Pertile D., Stratta E., Massobrio A., Soriero D., Nesbakken A., Lonn M., Backe I.F., Ferrari G., Mazzola M., Alampi B.D.A., Achilli P., Sfondrini S., Ioannidis O., Loutzidou L., Galanos-Demiris K., Pellino G., Balducci G., Frezza B., Lucarini A., Santos C., Cooper L., Siam B., Levy Y., Brenner B., Kashtan H., Belgrano V., De Cian F., Palermo B., Eggenhoffner R., Albertelli M., Sanchez-Guillen L., Arroyo A., Lopez-Rodriguez F., Lario S., Lillo C., Wexner S.D., Montroni, I., Rostoft, S., Spinelli, A., Van Leeuwen, B. L., Ercolani, G., Saur, N. M., Jacklitsh, M. T., Somasundar, P. S., de Liguori Carino, N., Ghignone, F., Foca, F., Zingaretti, C., Audisio, R. A., Ugolini, G., Garutti, A., Taffurelli, G., Zattoni, D., Tramelli, P., Sermonesi, G., Di Candido, F., Carvello, M., Sacchi, M., De Lucia, F., Foppa, C., Plas, M., Van der Wal-Huisman, H., Tauceri, F., Perenze, B., Di Pietrantonio, D., Mirarchi, M., Fejka, M., Bleier, J. I. S., Frain, L., Fox, S. W., Cardin, K., De Leon, L. E., Baltatzis, M., Chan, A. K. C., Siriwardena, A. K., Vertogen, B., Nanni, O., Garulli, G., Alagna, V., Pirrera, B., Lucchi, A., Monari, F., Conti, L., Capelli, P., Romboli, A., Palmieri, G., Banchini, F., Marano, L., Spaziani, A., Castagnoli, G., Bartoli, A., Trompetto, M., Gallo, G., Luc, A. R., Clerico, G., Sammarco, G., De Luca, R., Barile, G., Simone, M., Costanzi, A., Mari, G., Maggioni, M., Pellegrino, R., Riggio, V., Kenig, J., Szabat, K., Scabini, S., Pertile, D., Stratta, E., Massobrio, A., Soriero, D., Nesbakken, A., Lonn, M., Backe, I. F., Ferrari, G., Mazzola, M., Alampi, B. D. A., Achilli, P., Sfondrini, S., Ioannidis, O., Loutzidou, L., Galanos-Demiris, K., Pellino, G., Balducci, G., Frezza, B., Lucarini, A., Santos, C., Cooper, L., Siam, B., Levy, Y., Brenner, B., Kashtan, H., Belgrano, V., De Cian, F., Palermo, B., Eggenhoffner, R., Albertelli, M., Sanchez-Guillen, L., Arroyo, A., Lopez-Rodriguez, F., Lario, S., Lillo, C., and Wexner, S. D.

Subjects
Geriatric Oncology, Surgical Assessment, Functional Recovery, Pre&postoperative testing, Surgery morbidity, Surgery mortality, Male, medicine.medical_specialty, Surgery morbidity, MEDLINE, MULTICENTER, 03 medical and health sciences, 0302 clinical medicine, Postoperative Complications, Pre&postoperative testing, Quality of life, aged, aged, 80 and over, female, geriatric assessment, humans, male, neoplasms, postoperative complications, prospective studies, quality of life, Functional Recovery, Internal medicine, Neoplasms, medicine, 80 and over, Humans, 030212 general & internal medicine, Prospective Studies, Elective surgery, Geriatric Assessment, cancer, geriatric, outcome, Aged, Aged, 80 and over, business.industry, Surgical Assessment, Cancer, Functional recovery, medicine.disease, CANCER, Geriatric Oncology, Surgery mortality, Oncology, Geriatric oncology, 030220 oncology & carcinogenesis, Quality of Life, Observational study, Female, Geriatrics and Gerontology, business, Early analysis
Abstract

Objective: Older patients with cancer value functional outcomes as much as survival, but surgical studies lack functional recovery (FR) data. The value of a standardized frailty assessment has been confirmed, yet it's infrequently utilized due to time restrictions into everyday practice. The multicenter GOSAFE study was designed to (1) evaluate the trajectory of patients' quality of life (QoL) after cancer surgery (2) assess baseline frailty indicators in unselected patients (3) clarify the most relevant tools in predicting FR and clinical outcomes. This is a report of the study design and baseline patient evaluations. Materials & Methods: GOSAFE prospectively collected a baseline multidimensional evaluation before major elective surgery in patients (≥70 years) from 26 international units. Short−/mid−/long-term surgical outcomes were recorded with QoL and FR data. Results: 1003 patients were enrolled in a 26-month span. Complete baseline data were available for 977(97.4%). Median age was 78 years (range 70–94); 52.8% males. 968(99%) lived at home, 51.6% without caregiver. 54.4% had ≥ 3 medications, 5.9% none. Patients were dependent (ADL < 5) in 7.9% of the cases. Frailty was either detected by G8 ≤ 14(68.4%), fTRST ≥ 2(37.4%), TUG > 20 s (5.2%) or ASAIII-IV (48.8%). Major comorbidities (CACI > 6) were detected in 36%; 20.9% of patients had cognitive impairment according to Mini-Cog. Conclusion: The GOSAFE showed that frailty is frequent in older patients undergoing cancer surgery. QoL and FR, for the first time, are going to be primary outcomes of a real-life observational study. The crucial role of frailty assessment is going to be addressed in the ability to predict postoperative outcomes and to correlate with QoL and FR.

Published
2019

26. Pathology Reporting in Neuroendocrine Neoplasms of the Digestive System: Everything You Always Wanted to Know but Were Too Afraid to Ask

Author

Manuela Albertelli, Federica Grillo, Fabio Lo Calzo, Giulia Puliani, Carmen Rainone, Annamaria Anita Livia Colao, Antongiulio Faggiano, NIKE group, Barbara Altieri, Luigi Barrea, Filomena Bottiglieri, Severo Campione, Federica De Cicco, Sergio Di Molfetta, Alessandra Dicitore, Carlotta Dolci, Tiziana Feola, Giuseppe Fanciulli, Diego Ferone, Francesco Ferraù, Marco Gallo, Elisa Giannetta, Erika Grossrubatscher, Elia Guadagno, Valentina Guarnotta, Andrea M. Isidori, Andrea Lania, Andrea Lenzi, Pasquale Malandrino, Erika Messina, Roberta Modica, Giovanna Muscogiuri, Luca Pes, Genoveffa Pizza, Riccardo Pofi, Paola Razzore, Laura Rizza, Manila Rubino, Rosa Maria Ruggieri, Emilia Sbardella, Franz Sesti, Mary Anna Venneri, Giovanni Vitale, Maria Chiara Zatelli, Albertelli, M., Grillo, F., Lo Calzo, F., Puliani, G., Rainone, C., Colao, A. A. L., and Faggiano, A.

Subjects
0301 basic medicine, neuroendocrine classification, Endocrinology, Diabetes and Metabolism, Ki67, grade, immunohistochemistry, morphology, neuroendocrine neoplasms (NENs), pathology, 030209 endocrinology & metabolism, Neuroendocrine tumors, Digestive System Neoplasms, Diseases of the endocrine glands. Clinical endocrinology, 03 medical and health sciences, Endocrinology, 0302 clinical medicine, Multidisciplinary approach, Digestive System Neoplasm, Health care, Biomarkers, Tumor, medicine, Humans, Pathology reporting, Grading (tumors), Medical education, business.industry, RC648-665, Tumor Pathology, medicine.disease, Comprehension, Neuroendocrine Tumors, 030104 developmental biology, Ask price, Perspective, Neoplasm Grading, business, Psychology, Human
Abstract

During the 5th NIKE (Neuroendocrine tumors Innovation in Knowledge and Education) meeting, held in Naples, Italy, in May 2019, discussions centered on the understanding of pathology reports of gastroenetropancreactic neuroendocrine neoplasms. In particular, the main problem concerned the difficulty that clinicians experience in extrapolating relevant information from neuroendocrine tumor pathology reports. During the meeting, participants were asked to identify and rate issues which they have encountered, for which the input of an expert pathologist would have been appreciated. This article is a collection of the most rated questions and relative answers, focusing on three main topics: 1) morphology and classification; 2) Ki67 and grading; 3) immunohistochemistry. Patient management should be based on multidisciplinary decisions, taking into account clinical and pathology-related features with clear comprehension between all health care professionals. Indeed, pathologists require clinical details and laboratory findings when relevant, while clinicians require concise and standardized reports. In keeping with this last statement, the minimum requirements in pathology datasets are provided in this paper and should be a baseline for all neuroendocrine tumor professionals.

Published
2021
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27. Possible protective role of metformin therapy on colonic polyps in acromegaly: an exploratory cross-sectional study

Author

Elena Nazzari, S Ricci Bitti, Annamaria Colao, Manuela Albertelli, Rosario Pivonello, Rosa Pirchio, Ludovica F S Grasso, Andrea Dotto, Stefania Sciallero, Alberto Rebora, Mara Boschetti, Diego Ferone, Albertelli, M, Nazzari, E, Dotto, A, Grasso, L F, Sciallero, S, Pirchio, R, Rebora, A, Boschetti, M, Pivonello, R, Ricci Bitti, S, Colao, A A L, and Ferone, D

Subjects
Adult, Male, Risk, medicine.medical_specialty, Cross-sectional study, Acromegaly, Aged, Aged, 80 and over, Colonic Polyps, Colonoscopy, Cross-Sectional Studies, Female, Humans, Hypoglycemic Agents, Incidence, Metformin, Middle Aged, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Context (language use), Overweight, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Internal medicine, medicine, 80 and over, Cross-Sectional Studie, medicine.diagnostic_test, Hypoglycemic Agent, business.industry, Incidence (epidemiology), General Medicine, medicine.disease, Colonic Polyp, 030220 oncology & carcinogenesis, Population study, medicine.symptom, business, medicine.drug, Human
Abstract

Context Colonic polyps occur in 30–40% of acromegalic patients, increasing the risk of colon carcinoma. Although debated, there is emerging evidence that metformin may play a protective role in diabetic and non-diabetic patients with colonic polyps and its use in chemoprevention is currently explored. Objective Evaluate the prevalence of colonic polyps in acromegalic patients treated or not with metformin and explore its possible protective role. Design Exploratory cross-sectional study in two tertiary Italian referral centres. Met hods: Out of 153 acromegalic patients, we selected 58 patients (36–82 years; f: 33) who had at least one colonoscopy performed within the first 2 years of diagnosis. Presence of colonic polyps/cancer and related risk factors, current metformin and acetylsalicylic acid intake, disease duration, therapies for acromegaly, hormonal and metabolic parameters were assessed. Results An overall prevalence of 36% polyps was found. Based on the presence of polyps, we identified two groups, comparable for age, BMI, disease duration, glucose, insulin, HOMA-IR, HbA1c, GH and IGF-I levels. Of the patients with polyps (including three adenocarcinomas) only 24% were treated with metformin vs 57% of patients without polyps. Multivariate analysis confirmed a significant negative association between colonic polyps and metformin intake (OR: 0.22, 95% CI: 0.06-0.77, P = 0.01), whereas no significant association was found between polyps and age (P = 0.10), overweight/obesity (P = 0.54), smoking (P = 0.15), acetylsalicylic acid intake (P = 0.99), disease duration (P = 0.96), somatostatin analogues treatment (P = 0.70). Conclusions These findings, though deriving from an exploratory study, could suggest a protective role of metformin on the development of colonic polyps in acromegaly, and need to be confirmed in an extended study population.

Published
2020

28. PRRT: identikit of the perfect patient

Author

Annibale Versari, Pasqualino Malandrino, Roberta Modica, A. Colao, Diego Ferone, Antongiulio Faggiano, Andrea Dotto, Nike, C. Di Dato, Manuela Albertelli, Albertelli, M., Dotto, A., Di Dato, C., Malandrino, P., Modica, R., Versari, A., Colao, A., Ferone, D., and Faggiano, A.

Subjects
Oncology, medicine.medical_specialty, Liver tumor, Peptide receptor, Therapeutic sequence, Endocrinology, Diabetes and Metabolism, Therapeutic algorithm, Neuroendocrine tumors, Octreotide, Article, Peptide receptor radionuclide therapy, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Neuroendocrine tumor, Internal medicine, Positron Emission Tomography Computed Tomography, medicine, Organometallic Compounds, Humans, Grading (tumors), business.industry, Response, medicine.disease, Prognosis, Primary tumor, 030220 oncology & carcinogenesis, Predictor, Radionuclide therapy, Ki67 index, business
Abstract

Peptide receptor radionuclide therapy (PRRT) has been strengthened since the publication of NETTER-1. Nevertheless, the correct positioning in the therapeutic algorithm is debated, and no optimal sequence has yet been standardized. Possible criteria to predict the response to PRRT in neuroendocrine tumors (NET) have been proposed. The aim of this review is to define the perfect identity of the eligible patient who can mostly benefit from this therapy. Possible predictive criteria which have been analysed were: primary tumor site, grading, tumor burden, FDG PET and 68Ga-PET uptake. Primary tumor site and 68Ga-PET uptake do not play a pivotal role in predicting the response, while tumor burden, FDG PET uptake and grading seem to represent predictive/prognostic factors for response to PRRT. The heterogeneity in trial designs, patient populations, type of radionuclides, previous therapies and measurement of outcomes, inevitably limits the strength of our conclusions, therefore care must be taken in applying these results to clinical practice. In conclusion, the perfect patient, selected by 68Ga-PET uptake, will likely have a relatively limited liver tumor burden, a ki67 index

Published
2020

29. Potential indications for somatostatin analogues: immune system and limphoproliferative disorders

Author

Ferone, D., Resmini, E., Boschetti, M., Arvigo, M., Albanese, V., Ceresola, E., Pivonello, R., Manuela Albertelli, Bianchi, F., Giusti, M., Minuto, F., Ferone, D, Resmini, E, Boschetti, M, Arvigo, M, Albanese, V, Ceresola, E, Pivonello, Rosario, Albertelli, M, Bianchi, F, Giusti, M, and Minuto, F.

Subjects
limphoproliferative disorders, Immune System, Neuropeptides, Immunity, somatostatin analogue, Humans, Receptors, Somatostatin, Somatostatin, Lymphoproliferative Disorders
Abstract

Among hormones and neuropeptides influencing the immune system, somatostatin seems to play a key role not only in inhibiting specific immune cell activities, but also in promoting selected functions of particular immune cell subsets. Indeed, controversial effects have been observed in experimental conditions where somatostatin seems to stimulate certain cell functions, such as secretion of specific products (immunoglobulin, cytokines), cell migration and adhesion to extracellular matrix components. However, interestingly, cortistatin (CST), a neuropeptide that strongly resembles somatostatin, from both the structural and functional points of view, seems to have potential roles in regulating immune responses, as well as other lymphoid cell functions. The unexpected wide distribution of CST in a number of human organs, but particularly in immune cells, points to a broader physiological role of CST than previously presumed. The actions of somatostatin and its synthetic analogs (SSA) are mediated by five membrane G protein-coupled receptors subtypes (SSTR1-5), displaying a tissue specific distribution. The majority of somatostatin-target tissues, including lymphoid tissues, may co-express multiple somatostatin receptor (SSTR). The number of SSTRs in lymphoid cells is significantly lower compared to neuroendocrine tissues. However, the presence of receptors allowed the localization by in vivo SSTR scintigraphy of lymphoproliferative disorders, as well as granulomatous and autoimmune diseases. In specific cases, this technique may contribute to establishing the diagnosis and staging the disease. Recent studies evaluating the specific and quantitative SSTR distribution in lymphoid organs and cells, in both normal conditions and immune disorders, have largely contributed to better understand the phenomenology of in vivo receptor imaging and also the involvement of the different SSTR in determining the uptake of radiolabeled SSAs. Moreover, since lymphomas are highly radiosensitive malignancies, a promising approach in refractory patients with malignant lymphomas may be represented by radionuclide-targeted therapy with radioactive-coupled SSAs combined with gene therapy. This latter technique seems effective in inducing the expression or increasing the number of given SSTR in order to ameliorate the impact of radionuclide-targeted therapy. Medical treatment of lymphoproliferative diseases with currently available synthetic analogs have produced unsatisfactory and conflicting results. This might be due to the affinity of the current available SSAs for specific SSTR. However, the synthesis of new compounds with distinct properties has reopened a challenge in this field. The application of receptor-based localization and anti-tumor strategies should also be taking into account the new knowledge recently emerged on the physiopathology of neuropeptide receptors: firstly, neuropeptide receptor homo- and heterodimerization, which may involve different subtypes of SSTRs, as well as other neuropetide receptors, and secondly, the role of endogenous SSTR ligands, such as CST.

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