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27. Glucagon Secreting Tumors and Glucagonoma Syndrome

Author

Khalid, Y, Ozair, F, Du Parc, J, Beharry, N, Mudan, S, and Bano, G

Subjects
endocrine system diseases
Abstract

Glucagonomas are the functioning neuroendocrine tumors. These arise from pancreatic islet α-cells. These tumors are extremely rare and have an annual incidence of 1 per 20-40 million population 80% of glucagon-expressing tumors are sporadic, and 20% are associated with genetic syndromes such as Multiple Endocrine Neoplasia-type 1. Glucagonoma typically occurs in the distal pancreas, and around 85% are in the body or tail. It tends to be large at the time of diagnosis. Most reported cases of glucagonoma are malignant and about 65-75% patients present with metastatic disease. The liver is usually the first site of metastases, followed by the involvement of peripancreatic lymph nodes. The term Glucagonoma syndrome and glucagonoma are often interchangeably used, but in fact, these are two distinct entities. Glucagonoma syndrome comprises of necrolytic migratory erythema, hyperglucagonemia, diabetes mellitus, anemia, weight loss, glossitis, diarrhea, venous thrombosis and neuropsychiatric disturbances in the presence of a glucagon-producing tumor of the pancreas. Tumors secreting glucagon can occur without the glucagonoma syndrome. The glucagonoma secretion depends on the expression of protein convertase enzyme PC1/3 or PC2 within the tumor itself. As a result of this expression, the clinical manifestations can be variable. The tumor can either present with hyperinsulinemic hypoglycemia in a patient with a previous history of diabetes or with the features of the glucagonoma syndrome. In cases where a tumor is localized surgery is the curative treatment. Reduction of the tumor bulk, removal of the primary by surgery and targeted therapy for the hepatic metastases are the favored approach even when there is the metastasis.

Published
2017

29. Bevacizumab plus mFOLFOX-6 or FOLFOXIRI in patients with initially unresectable liver metastases from colorectal cancer: the OLIVIA multinational randomised phase II trial

Author

Gruenberger, T., Bridgewater, J., Chau, I., García Alfonso, P., Rivoire, M., Mudan, S., Lasserre, S., Hermann, F., Waterkamp, D., Adam, R., Gruenberger, T., Bridgewater, J., Chau, I., García Alfonso, P., Rivoire, M., Mudan, S., Lasserre, S., Hermann, F., Waterkamp, D., and Adam, R.

Abstract

OLIVIA, a multinational phase II study, suggests that bevacizumab plus FOLFOXIRI improves outcomes, including response rates, resection rates, and progression-free survival, compared with bevacizumab plus mFOLFOX-6 in patients with initially unresectable liver metastases from colorectal cancer

Published
2017

30. Surgical quality and the impact of liver resection on outcome in the new EPOC study

Author

Pugh, S., primary, Bridgewater, J., additional, Finch-Jones, M., additional, Rees, M., additional, O'Reilly, D., additional, Peterson, M., additional, Davidson, B., additional, Hutchins, R., additional, Heaton, N., additional, Jiao, L.R., additional, Mudan, S., additional, Allen, A., additional, Mellor, J., additional, Griffiths, G., additional, Cunningham, D., additional, Maughan, T., additional, Garden, J., additional, and Primrose, J., additional

Published
2017
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32. Corrigendum: Randomised, open-label, phase II study of gemcitabine with and without IMM-101 for advanced pancreatic cancer (British Journal of Cancer (2016) 115 (789-796) DOI: 10.1038/bjc.2016.271)

Author

Dalgleish, A, Stebbing, J, Adamson, D, Arif, S, Bidoli, P, Chang, D, Cheeseman, S, Diaz-Beveridge, R, Fernandez-Martos, C, Glynne-Jones, R, Granetto, C, Massuti, B, Mcadam, K, Mcdermott, R, Martín, A, Papamichael, D, Pazo-Cid, R, Vieitez, J, Zaniboni, A, Carroll, K, Wagle, S, Gaya, A, Mudan, S, Dalgleish AG, Stebbing J, Adamson DJ, Arif SS, Bidoli P, Chang D, Cheeseman S, Diaz-Beveridge R, Fernandez-Martos C, Glynne-Jones R, Granetto C, Massuti B, McAdam K, McDermott R, Martín AJ, Papamichael D, Pazo-Cid R, Vieitez JM, Zaniboni A, Carroll KJ, Wagle S, Gaya A, Mudan SS., Dalgleish, A, Stebbing, J, Adamson, D, Arif, S, Bidoli, P, Chang, D, Cheeseman, S, Diaz-Beveridge, R, Fernandez-Martos, C, Glynne-Jones, R, Granetto, C, Massuti, B, Mcadam, K, Mcdermott, R, Martín, A, Papamichael, D, Pazo-Cid, R, Vieitez, J, Zaniboni, A, Carroll, K, Wagle, S, Gaya, A, Mudan, S, Dalgleish AG, Stebbing J, Adamson DJ, Arif SS, Bidoli P, Chang D, Cheeseman S, Diaz-Beveridge R, Fernandez-Martos C, Glynne-Jones R, Granetto C, Massuti B, McAdam K, McDermott R, Martín AJ, Papamichael D, Pazo-Cid R, Vieitez JM, Zaniboni A, Carroll KJ, Wagle S, Gaya A, and Mudan SS.

Abstract

Upon publication of the above paper in the British Journal of Cancer, the authors identified an error in one of their affiliations. The authors would like to apologise for this mistake. The correct affiliation for Andrés J Munoz Martín is 'Medical Oncology Service, Hospital General Universitario Gregorio Maranón, Madrid, Spain.'

Published
2016

33. Corrigendum: Randomised, open-label, phase II study of gemcitabine with and without IMM-101 for advanced pancreatic cancer (British Journal of Cancer (2016) 115 (789-796) DOI: 10.1038/bjc.2016.271)

Author

Dalgleish AG, Dalgleish, A, Stebbing, J, Adamson, D, Arif, S, Bidoli, P, Chang, D, Cheeseman, S, Diaz-Beveridge, R, Fernandez-Martos, C, Glynne-Jones, R, Granetto, C, Massuti, B, Mcadam, K, Mcdermott, R, Martín, A, Papamichael, D, Pazo-Cid, R, Vieitez, J, Zaniboni, A, Carroll, K, Wagle, S, Gaya, A, Mudan, S, Dalgleish AG, Stebbing J, Adamson DJ, Arif SS, Bidoli P, Chang D, Cheeseman S, Diaz-Beveridge R, Fernandez-Martos C, Glynne-Jones R, Granetto C, Massuti B, McAdam K, McDermott R, Martín AJ, Papamichael D, Pazo-Cid R, Vieitez JM, Zaniboni A, Carroll KJ, Wagle S, Gaya A, Mudan SS., Dalgleish AG, Dalgleish, A, Stebbing, J, Adamson, D, Arif, S, Bidoli, P, Chang, D, Cheeseman, S, Diaz-Beveridge, R, Fernandez-Martos, C, Glynne-Jones, R, Granetto, C, Massuti, B, Mcadam, K, Mcdermott, R, Martín, A, Papamichael, D, Pazo-Cid, R, Vieitez, J, Zaniboni, A, Carroll, K, Wagle, S, Gaya, A, Mudan, S, Dalgleish AG, Stebbing J, Adamson DJ, Arif SS, Bidoli P, Chang D, Cheeseman S, Diaz-Beveridge R, Fernandez-Martos C, Glynne-Jones R, Granetto C, Massuti B, McAdam K, McDermott R, Martín AJ, Papamichael D, Pazo-Cid R, Vieitez JM, Zaniboni A, Carroll KJ, Wagle S, Gaya A, and Mudan SS.

Abstract

Upon publication of the above paper in the British Journal of Cancer, the authors identified an error in one of their affiliations. The authors would like to apologise for this mistake. The correct affiliation for Andrés J Munoz Martín is 'Medical Oncology Service, Hospital General Universitario Gregorio Maranón, Madrid, Spain.'

Published
2016

34. Randomised, open-label, phase II study of gemcitabine with and without IMM-101 for advanced pancreatic cancer

Author

Dalgleish, A, Stebbing, J, Adamson, D, Arif, S, Bidoli, P, Chang, D, Cheeseman, S, Diaz-Beveridge, R, Fernandez-Martos, C, Glynne-Jones, R, Granetto, C, Massuti, B, Mcadam, K, Mcdermott, R, Martín, A, Papamichael, D, Pazo-Cid, R, Vieitez, J, Zaniboni, A, Carroll, K, Wagle, S, Gaya, A, Mudan, S, Dalgleish AG, Stebbing J, Adamson DJ, Arif SS, Bidoli P, Chang D, Cheeseman S, Diaz-Beveridge R, Fernandez-Martos C, Glynne-Jones R, Granetto C, Massuti B, McAdam K, McDermott R, Martín AJ, Papamichael D, Pazo-Cid R, Vieitez JM, Zaniboni A, Carroll KJ, Wagle S, Gaya A, Mudan SS, Dalgleish, A, Stebbing, J, Adamson, D, Arif, S, Bidoli, P, Chang, D, Cheeseman, S, Diaz-Beveridge, R, Fernandez-Martos, C, Glynne-Jones, R, Granetto, C, Massuti, B, Mcadam, K, Mcdermott, R, Martín, A, Papamichael, D, Pazo-Cid, R, Vieitez, J, Zaniboni, A, Carroll, K, Wagle, S, Gaya, A, Mudan, S, Dalgleish AG, Stebbing J, Adamson DJ, Arif SS, Bidoli P, Chang D, Cheeseman S, Diaz-Beveridge R, Fernandez-Martos C, Glynne-Jones R, Granetto C, Massuti B, McAdam K, McDermott R, Martín AJ, Papamichael D, Pazo-Cid R, Vieitez JM, Zaniboni A, Carroll KJ, Wagle S, Gaya A, and Mudan SS

Abstract

Background: Immune Modulation and Gemcitabine Evaluation-1, a randomised, open-label, phase II, first-line, proof of concept study (NCT01303172), explored safety and tolerability of IMM-101 (heat-killed Mycobacterium obuense; NCTC 13365) with gemcitabine (GEM) in advanced pancreatic ductal adenocarcinoma. Methods: Patients were randomised (2: 1) to IMM-101 (10 mg ml -l intradermally)+GEM (1000 mg m -2 intravenously; n=75), or GEM alone (n=35). Safety was assessed on frequency and incidence of adverse events (AEs). Overall survival (OS), progression-free survival (PFS) and overall response rate (ORR) were collected. Results: IMM-101 was well tolerated with a similar rate of AE and serious adverse event reporting in both groups after allowance for exposure. Median OS in the intent-to-treat population was 6.7 months for IMM-101+GEM v 5.6 months for GEM; while not significant, the hazard ratio (HR) numerically favoured IMM-101+GEM (HR, 0.68 (95% CI, 0.44-1.04, P=0.074). In a pre-defined metastatic subgroup (84%), OS was significantly improved from 4.4 to 7.0 months in favour of IMM-101+GEM (HR, 0.54, 95% CI 0.33-0.87, P=0.01). Conclusions: IMM-101 with GEM was as safe and well tolerated as GEM alone, and there was a suggestion of a beneficial effect on survival in patients with metastatic disease. This warrants further evaluation in an adequately powered confirmatory study.

Published
2016

40. Многоцентровое исследование эффективности неоадъювантной терапии САРОХ/бевацизумаб у неоперабельных больных с метастазами колоректального рака в печени

Author

Wong, R., Cunningham, D., Barbachano, Y., Saffery, C., Valle, J., Hickish, T., Mudan, S., Brown, G., Khan, A., Wotherspoon, A., Strimpakos, A.S., Thomas, J., Compton, S., Chua, Y.J., and Chau, I.

Subjects
Международный опыт
Abstract

Проанализированы результаты многоцентрового исследования II фазы, в котором показана эффективность и безопасность комбинации режима CAPOX с бевацизумабом при неоадъювантной терапии не подлежащих хирургическому лечению пациентов с метастазами колоректального рака в печени: резектабельность последних была достигнута в 44% случаев, 12-месячная выживаемость: общая – 96%, безрецидивная – 50%. Ключевые слова: колоректальный рак, метастазы в печени, бевацизумаб, капецитабин, оксалиплатин. The results of multicentre study of II phase are analyzed. The efficacy and safety of combined regimen CAPOX + bevacizumab in adjuvant therapy of patients not selected for upfront resection and with colorectal cancer metastasis in liver is demonstrated. The respectability was achieved in 44% of cases, 12-month survival, overall, survival 96%, without relapse 50%. Key Words: bevacizumab, capecitabine, colorectal cancer, liver metastases, oxaliplatin

Published
2011

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