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7. Colorectal Neuroendocrine Neoplasms

Author

Ramage, John K., Valle, Juan W., van Dijkum, Els J. M. Nieveen, Sundin, Anders, Pascher, Andreas, Couvelard, Anne, Kloeppel, Guenter, Bartsch, Detlef, Arnold, Rudolf, Baudin, Eric, Bodei, Lisa, Borbath, Iva, Capdevila, Jaume, Caplin, Matyn, Chen, Jie, Costa, Frederico, Cwikla, Jaroslaw B., Davies, Philippa, de Herder, Wouter W., Falconi, Massimo, Falkerby, Jenny, Fazio, Nicola, Ferone, Diego, Frilling, Andrea, Garcia-Carbonero, Rocio, Glasberg, Simona, Gorbunova, Vera, Grossman, Ashley, Hoersch, Dieter, Jensen, Robert, Kaltsas, Gregory, Kingge, Ulrich Peter, Kos-Kudla, Beata, Krejs, Guenter J., Krenning, Eric, Kulke, Matthew, Lamberts, Steven W. J., Van Dijkum, Nieveen Els J. M., O'Connor, Juan Manuel, O'Toole, Dermot, Pape, Ulrich-Frank, Partelli, Stefano, Pavel, Marianne Ellen, Peeters, Marc, Reed, Nicholas Simon, Rindi, Guido, Rinke, Anja, Ruszniewski, Philippe, Sorbye, Halfdan, Scoazec, Jean-Yves, Taal, Babs G., Janson, Tiensuu Eva, Toumpanakis, Christos, Vullierme, Marie-Pierre, Staffan, Welin, Wiedenmann, Bertman, ENETS 2016 Munich Advisory Board, Ramage, Jk, Valle, Jw, Nieveen, Van Dijkum EJM, Sundin, A, Pascher, A, Couvelard, A, Kloeppel, G, on behalf of The ENETS 2016 MunichAdvisory Board, Partecipant, Partelli, S, Falconi, M, Internal Medicine, and Radiology & Nuclear Medicine

Subjects
Gastroenteropancreatic neuroendocrine tumour, Oncology, medicine.medical_specialty, Biomedical Research, Colorectal cancer, Endocrinology, Diabetes and Metabolism, Carcinoid tumour, Improved survival, 030209 endocrinology & metabolism, World health, Somatostatin receptor, 030218 nuclear medicine & medical imaging, Unmet needs, 03 medical and health sciences, Cellular and Molecular Neuroscience, Biomedical Research/trends, 0302 clinical medicine, Endocrinology, Internal medicine, Neuroendocrine tumour, Epidemiology, medicine, Colorectal Neoplasms/classification, Humans, Stage (cooking), Endocrine and Autonomic Systems, business.industry, Poorly differentiated, medicine.disease, digestive system diseases, Neuroendocrine Tumors, Neuroendocrine Tumors/classification, Human medicine, business, Colorectal Neoplasms
Abstract

The subject of colorectal neuroendocrine neoplasms (NENs), subdivided into well-differentiated NENs, termed neuroendocrine tumours (NETs; grade (G) 1 and 2), and poorly differentiated NENs, termed neuroendocrine carcinomas (NECs; G3) according to the 2010 World Health Organisation (WHO) classification, has arguably not had as much attention or study as NENs occurring in other sites. Colorectal NETs and NECs are however easier to study than many others since they are usually not difficult to remove and are increasingly detected because of intensified colorectal cancer screening and surveillance programmes. Colorectal NETs and NECs show site-specific heterogeneity with variable behaviour and different therapeutic options; these various aspects provide unique challenges. Because of bowel cancer screening programmes, colorectal NENs, like conventional adenocarcinomas, may be diagnosed at a stage that is associated with improved survival. In this article we intend to describe and define areas of unmet needs relating to the epidemiology, classification, pathology, diagnosis and therapy of colorectal NETs (including NETs G3), colorectal NECs, and finally, mixed adeno-neuroendocrine carcinomas (MANECs) by reviewing and discussing the relevant literature.

Published
2019

9. Colorectal Neuroendocrine Neoplasms: Areas of Unmet Need

Author

Ramage, John K. Valle, Juan W. van Dijkum, Els J. M. Nieveen and Sundin, Anders Pascher, Andreas Couvelard, Anne Kloeppel, Guenter Bartsch, Detlef Arnold, Rudolf Baudin, Eric and Bodei, Lisa Borbath, Iva Capdevila, Jaume Caplin, Matyn and Chen, Jie Costa, Frederico Couvelard, Anne Cwikla, Jaroslaw B. Davies, Philippa de Herder, Wouter W. Falconi, Massimo and Falkerby, Jenny Fazio, Nicola Ferone, Diego Frilling, Andrea Garcia-Carbonero, Rocio Glasberg, Simona Gorbunova, Vera Grossman, Ashley Hoersch, Dieter Jensen, Robert and Kaltsas, Gregory Kloeppel, Guenter Kingge, Ulrich Peter and Kos-Kudla, Beata Krejs, Guenter J. Krenning, Eric Kulke, Matthew Lamberts, Steven W. J. Van Dijkum, Nieveen Els J. M. and O'Connor, Juan Manuel O'Toole, Dermot Pape, Ulrich-Frank and Partelli, Stefano Pavel, Marianne Ellen Peeters, Marc and Ramage, John K. Reed, Nicholas Simon Rindi, Guido Rinke, Anja Ruszniewski, Philippe Sorbye, Halfdan Sundin, Anders and Scoazec, Jean-Yves Taal, Babs G. Janson, Tiensuu Eva and Toumpanakis, Christos Valle, Juan W. Vullierme, Marie-Pierre and Staffan, Welin Wiedenmann, Bertman ENETS 2016 Munich Advisory Board

Subjects
digestive system diseases
Abstract

The subject of colorectal neuroendocrine neoplasms (NENs), subdivided into well-differentiated NENs, termed neuroendocrine tumours (NETs; grade (G) 1 and 2), and poorly differentiated NENs, termed neuroendocrine carcinomas (NECs; G3) according to the 2010 World Health Organisation (WHO) classification, has arguably not had as much attention or study as NENs occurring in other sites. Colorectal NETs and NECs are however easier to study than many others since they are usually not difficult to remove and are increasingly detected because of intensified colorectal cancer screening and surveillance programmes. Colorectal NETs and NECs show site-specific heterogeneity with variable behaviour and different therapeutic options; these various aspects provide unique challenges. Because of bowel cancer screening programmes, colorectal NENs, like conventional adenocarcinomas, may be diagnosed at a stage that is associated with improved survival. In this article we intend to describe and define areas of unmet needs relating to the epidemiology, classification, pathology, diagnosis and therapy of colorectal NETs (including NETs G3), colorectal NECs, and finally, mixed adeno-neuroendocrine carcinomas (MANECs) by reviewing and discussing the relevant literature.

Published
2019

10. Management of Asymptomatic Sporadic Nonfunctioning Pancreatic Neuroendocrine Neoplasms (ASPEN) ≤2 cm: Study Protocol for a Prospective Observational Study

Author

Partelli, Stefano, primary, Ramage, John K., additional, Massironi, Sara, additional, Zerbi, Alessandro, additional, Kim, Hong Beom, additional, Niccoli, Patricia, additional, Panzuto, Francesco, additional, Landoni, Luca, additional, Tomazic, Ales, additional, Ibrahim, Toni, additional, Kaltsas, Gregory, additional, Bertani, Emilio, additional, Sauvanet, Alain, additional, Segelov, Eva, additional, Caplin, Martyn, additional, Coppa, Jorgelina, additional, Armstrong, Thomas, additional, Weickert, Martin O., additional, Butturini, Giovanni, additional, Staettner, Stefan, additional, Boesch, Florian, additional, Cives, Mauro, additional, Moulton, Carol Anne, additional, He, Jin, additional, Selberherr, Andreas, additional, Twito, Orit, additional, Castaldi, Antonio, additional, De Angelis, Claudio Giovanni, additional, Gaujoux, Sebastien, additional, Almeamar, Hussein, additional, Frilling, Andrea, additional, Vigia, Emanuel, additional, Wilson, Colin, additional, Muffatti, Francesca, additional, Srirajaskanthan, Raj, additional, Invernizzi, Pietro, additional, Lania, Andrea, additional, Kwon, Wooil, additional, Ewald, Jacques, additional, Rinzivillo, Maria, additional, Nessi, Chiara, additional, Smid, Lojze M., additional, Gardini, Andrea, additional, Tsoli, Marina, additional, Picardi, Edgardo E., additional, Hentic, Olivia, additional, Croagh, Daniel, additional, Toumpanakis, Christos, additional, Citterio, Davide, additional, Ramsey, Emma, additional, Mosterman, Barbara, additional, Regi, Paolo, additional, Gasteiger, Silvia, additional, Rossi, Roberta E., additional, Smiroldo, Valeria, additional, Jang, Jin-Young, additional, and Falconi, Massimo, additional

Published
2020
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14. Tumour diameter is not reliable for management of non-secreting pancreatic neuroendocrine tumours

Author

Mills, Logan, primary, Drymousis, Panagiotis, additional, Vashist, Yogesh, additional, Burdelski, Christoph, additional, Prachalias, Andreas, additional, Srinivasan, Parthi, additional, Menon, Krishna, additional, Cotoi, Corina, additional, Khan, Saboor, additional, Cave, Judith, additional, Armstrong, Thomas, additional, Weickert, Martin O, additional, Izbicki, Jakob, additional, Schrader, Joerg, additional, Frilling, Andreja, additional, Ramage, John K, additional, and Srirajaskanthan, Raj, additional

Published
2017
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15. Vindaloo And You [with Reply]

Author

Ramage, John K., Hunt, Richard H., Ayres, Jon G., Bjarnason, Ingvar, Levi, Sassoon, Smethurst, Paul, Menzies, Ian S., and Levi, A. Jonathan

Published
1989

16. Tumour Size is not a Reliable Criterion for Resection of Patients with Non-Secreting Pancreatic Neuroendocrine Tumours: Results of an International, Multi-Centre, Operative Cohort

Author

Mills, Logan, primary, Drymousis, Panagiotis, additional, Vashist, Yogesh, additional, Burdelski, Christoph, additional, Prachalias, Andreas, additional, Srinivasan, Parthi, additional, Menon, Krishna, additional, Khan, Saboor, additional, Cave, Judith, additional, Armstrong, Thomas, additional, Weickert, Martin O., additional, Frilling, Andrea, additional, Ramage, John K., additional, and Srirajaskanthan, Raj, additional

Published
2017
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17. A Multimodal Approach to the Management of Neuroendocrine Tumour Liver Metastases

Author

Basuroy, Ron, Srirajaskanthan, Rajaventhan, and Ramage, John K.

Subjects
Article Subject
Abstract

Neuroendocrine tumours (NETs) are often indolent malignancies that commonly present with metastatic disease in the liver. Surgical, locoregional, and systemic treatment modalities are reviewed. A multidisciplinary approach to patient care is suggested to ensure all therapeutic options explored.

Published
2012
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19. 1022 - Tumour Size is not a Reliable Criterion for Resection of Patients with Non-Secreting Pancreatic Neuroendocrine Tumours: Results of an International, Multi-Centre, Operative Cohort

Author

Mills, Logan, Drymousis, Panagiotis, Vashist, Yogesh, Burdelski, Christoph, Prachalias, Andreas, Srinivasan, Parthi, Menon, Krishna, Khan, Saboor, Cave, Judith, Armstrong, Thomas, Weickert, Martin O., Frilling, Andrea, Ramage, John K., and Srirajaskanthan, Raj

Published
2017
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24. Effect of immunologic reactions on rat intestinal epithelium

Author

Ramage, John K., Stanisz, Andrzej, Scicchitano, Raphaele, Hunt, Richard H., and Perdue, Mary H.

Abstract

In these studies we compared jejunal permeability to two probes—chromium 51-labeled ethylenediaminetetraacetic acid (51Cr-EDTA) (mol wt, 360) and ovalbumin (mol wt, 45,000)—under control conditions, during acute intestinal inflammation, and in response to systemic anaphylaxis. Acute inflammation was produced after infection with Nippostrongylus brasiliensisand rats were studied at day 0 (control), day 4 (early), day 10 (acute), and day 35 (postinfection). At the latter stage, immune rats were also studied during anaphylaxis induced by i.v. N. brasiliensisantigen. In each study, blood and urine were sampled over 5 h after the probes were simultaneously injected into ligated loops in anesthetized rats. In controls, small quantities (<0.04% and 0.002% of the administered dose for 51Cr-EDTA and ovalbumin, respectively) appeared in the circulation and plateaued at 1 h. During acute inflammation, the appearance of both probes continued to increase with time. Compared with controls, 5-h values for 51Cr-EDTA and ovalbumin were (a) significantly elevated at day 4 (p < 0.005), (b) increased ~20-fold at day 10 (p < 0.005 and <0.01, respectively), and (c) normal at day 35. Urinary recovery of 51Cr-EDTA followed the same pattern. During anaphylaxis, appearance of the probes in the circulation increased at 1 h to values ~10-fold those in controls (p < 0.001 and <0.01, for 51Cr-EDTA and ovalbumin, respectively), and then declined. Urinary recovery of 51Cr-EDTA over 5 h was also significantly increased. We conclude that epithelial barrier function becomes impaired during both acute inflammation and anaphylaxis. In this rat model, gut permeability changes to 51Cr-EDTA reflect gut permeability changes to macromolecular antigens. If similar conditions exist in humans, urinary recovery of 51Cr-EDTA may be useful in monitoring intestinal abnormalities associated with inflammation.

Published
1988
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25. Calcitonin secreting neuroendocrine neoplasms of the lung: a systematic review and narrative synthesis

Author

Llewellyn, David, Srirajaskanthan, Rajaventhan, Vincent, Royce, Guy, Catherine, Drakou, Eftychia E, Aylwin, Simon, Grossman, Ashley, Ramage, John K, and Dimitriadis, Georgios K

Abstract

Calcitonin-secreting neuroendocrine neoplasms of the lung are rare, with few cases reported in the literature. Differentiating between medullary thyroid carcinoma and an ectopic source of calcitonin secretion can represent a complex diagnostic conundrum for managing physicians, with cases of unnecessary thyroidectomy reported in the literature. This manuscript reports a case of ectopic hypercalcitonaemia from a metastatic neuroendocrine neoplasm of the lung with concurrent thyroid pathology and summarises the results of a systematic review of the literature. Medical Literature Analysis and Retrieval System Online, Excerpta Medica, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov and SCOPUS databases were systematically and critically appraised for all peer reviewed manuscripts that suitably fulfilled the inclusion criteria established a priori. The protocol for this systematic review was developed according to the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols, and followed methods outlined in The Cochrane Handbook for Systematic Reviews of Interventions. This systematic review is registered with PROSPERO. It is vital to consider diagnoses other than medullary thyroid carcinoma when presented with a patient with raised calcitonin, as it is not pathognomonic of medullary thyroid carcinoma. Lung neuroendocrine neoplasms can appear similar to medullary thyroid carcinoma histologically, they can secrete calcitonin and metastasize to the thyroid. Patients with medullary thyroid carcinoma may show stimulated calcitonin values over two or more times above the basal values, whereas calcitonin-secreting neuroendocrine neoplasms may or may not show response to stimulation tests. The present review summarises existing evidence from cases of ectopic hypercalcitonaemia to lung neuroendocrine neoplasms.

Published
2019
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26. Management of Asymptomatic Sporadic Nonfunctioning Pancreatic Neuroendocrine Neoplasms (ASPEN) ≤2 cm: Study Protocol for a Prospective Observational Study

Author

Stefano Partelli, John K. Ramage, Sara Massironi, Alessandro Zerbi, Hong Beom Kim, Patricia Niccoli, Francesco Panzuto, Luca Landoni, Ales Tomazic, Toni Ibrahim, Gregory Kaltsas, Emilio Bertani, Alain Sauvanet, Eva Segelov, Martyn Caplin, Jorgelina Coppa, Thomas Armstrong, Martin O. Weickert, Giovanni Butturini, Stefan Staettner, Florian Boesch, Mauro Cives, Carol Anne Moulton, Jin He, Andreas Selberherr, Orit Twito, Antonio Castaldi, Claudio Giovanni De Angelis, Sebastien Gaujoux, Hussein Almeamar, Andrea Frilling, Emanuel Vigia, Colin Wilson, Francesca Muffatti, Raj Srirajaskanthan, Pietro Invernizzi, Andrea Lania, Wooil Kwon, Jacques Ewald, Maria Rinzivillo, Chiara Nessi, Lojze M. Smid, Andrea Gardini, Marina Tsoli, Edgardo E. Picardi, Olivia Hentic, Daniel Croagh, Christos Toumpanakis, Davide Citterio, Emma Ramsey, Barbara Mosterman, Paolo Regi, Silvia Gasteiger, Roberta E. Rossi, Valeria Smiroldo, Jin-Young Jang, Massimo Falconi, Partelli, S, Ramage, J, Massironi, S, Zerbi, A, Kim, H, Niccoli, P, Panzuto, F, Landoni, L, Tomazic, A, Ibrahim, T, Kaltsas, G, Bertani, E, Sauvanet, A, Segelov, E, Caplin, M, Coppa, J, Armstrong, T, Weickert, M, Butturini, G, Staettner, S, Boesch, F, Cives, M, Moulton, C, He, J, Selberherr, A, Twito, O, Castaldi, A, De Angelis, C, Gaujoux, S, Almeamar, H, Frilling, A, Vigia, E, Wilson, C, Muffatti, F, Srirajaskanthan, R, Invernizzi, P, Lania, A, Kwon, W, Ewald, J, Rinzivillo, M, Nessi, C, Smid, L, Gardini, A, Tsoli, M, Picardi, E, Hentic, O, Croagh, D, Toumpanakis, C, Citterio, D, Ramsey, E, Mosterman, B, Regi, P, Gasteiger, S, Rossi, R, Smiroldo, V, Jang, J, Falconi, M, Partelli, Stefano, Ramage, John K, Massironi, Sara, Zerbi, Alessandro, Kim, Hong Beom, Niccoli, Patricia, Panzuto, Francesco, Landoni, Luca, Tomazic, Ale, Ibrahim, Toni, Kaltsas, Gregory, Bertani, Emilio, Sauvanet, Alain, Segelov, Eva, Caplin, Martyn, Coppa, Jorgelina, Armstrong, Thoma, Weickert, Martin O, Butturini, Giovanni, Staettner, Stefan, Boesch, Florian, Cives, Mauro, Moulton, Carol Anne, He, Jin, Selberherr, Andrea, Twito, Orit, Castaldi, Antonio, De Angelis, Claudio Giovanni, Gaujoux, Sebastien, Almeamar, Hussein, Frilling, Andrea, Vigia, Emanuel, Wilson, Colin, Muffatti, Francesca, Srirajaskanthan, Raj, Invernizzi, Pietro, Lania, Andrea, Kwon, Wooil, Ewald, Jacque, Rinzivillo, Maria, Nessi, Chiara, Smid, Lojze M, Gardini, Andrea, Tsoli, Marina, Picardi, Edgardo E, Hentic, Olivia, Croagh, Daniel, Toumpanakis, Christo, Citterio, Davide, Ramsey, Emma, Mosterman, Barbara, Regi, Paolo, Gasteiger, Silvia, Rossi, Roberta E, Smiroldo, Valeria, Jang, Jin-Young, and Falconi, Massimo

Subjects
lcsh:R5-920, medicine.medical_specialty, Surgical approach, business.industry, Optimal treatment, Nodule (medicine), General Medicine, small nonfunctioning pancreatic neuroendocrine neoplasm, Asymptomatic, NF-PanNEN_2 cm, HCC CHBPT, ASPEN study, surgery, Study Protocol, aspen study, follow-up, management, nf-pannen_2 cm, surveillance, medicine, Medicine, Observational study, Radiology, medicine.symptom, lcsh:Medicine (General), business
Abstract

Introduction: The optimal treatment for small, asymptomatic, nonfunctioning pancreatic neuroendocrine neoplasms (NF-PanNEN) is still controversial. European Neuroendocrine Tumor Society (ENETS) guidelines recommend a watchful strategy for asymptomatic NF-PanNEN Methods: ASPEN is a prospective international observational multicentric cohort study supported by ENETS. The study is registered in ClinicalTrials.gov with the identification code NCT03084770. Based on the incidence of NF-PanNEN the number of expected patients to be enrolled in the ASPEN study is 1,000 during the study period (2017–2022). Primary endpoint is disease/progression-free survival, defined as the time from study enrolment to the first evidence of progression (active surveillance group) or recurrence of disease (surgery group) or death from disease. Inclusion criteria are: age >18 years, the presence of asymptomatic sporadic NF-PanNEN ≤2 cm proven by a positive fine-needle aspiration (FNA) or by the presence of a measurable nodule on high-quality imaging techniques that is positive at 68Gallium DOTATOC-PET scan.Conclusion: The ASPEN study is designed to investigate if an active surveillance of asymptomatic NF-PanNEN ≤2 cm is safe as compared to surgical approach.

Published
2020

27. Incidence and survival of neuroendocrine neoplasia in England 1995-2018: A retrospective, population-based study.

Author

White BE, Rous B, Chandrakumaran K, Wong K, Bouvier C, Van Hemelrijck M, George G, Russell B, Srirajaskanthan R, and Ramage JK

Abstract

Background: Neuroendocrine neoplasia (NEN) incidence is rising internationally. We aimed to evaluate the epidemiology of NEN in England and examine changes in survival over time., Methods: A retrospective, population-based study using nationally representative data between 1995 and 2018 from the National Cancer Registry and Analysis Service (NCRAS) in England was conducted on 63,949 tumours. Age-standardized incidence was calculated using Office for National Statistics (ONS) data. Overall survival (OS) was calculated using the Kaplan-Meier estimator. Multivariable analysis was performed using an accelerated failure time model., Findings: Of 63,949 cases, 50.5% (32,309) were female. Age-adjusted incidence increased 3.7-fold between 1995 and 2018 from 2.35 to 8.61 per 100,000. In 2018, highest incidence occurred in lung (1.47 per 100,000), small intestine (1.46 per 100,000), pancreas (1.00 per 100,000) and appendix (0.95 per 100,000). In multivariable analysis, age, sex, morphology, stage, site and deprivation were independent predictors of survival ( p  < 0.001). Survival of the entire cohort, and by primary site, is improving over time., Interpretation: NEN incidence continues to rise in England with survival improving over time. Relatively high survival compared to other cancers is an issue for long-term outcomes and funding of care., Funding: Data were extracted and transferred using a grant from Neuroendocrine cancer UK., Competing Interests: JKR supervised securing funding for the grant from Neuroendocrine Cancer UK (NCUK) to process the data in the initial planning of the work. CB states that NCUK receives donation, grant and sponsorship money from patients, businesses and not-for-profit organisations. CB is a board member of the International Neuroendocrine Cancer Alliance (INCA). The other authors declare no conflict of interest., (© 2022 The Authors.)

Published
2022
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