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Rossi R.E.,Neuroendocrine Tumour Unit | Rossi R.E.,University of Milan | Burroughs A.K.,University College London | Caplin M.E.,Neuroendocrine Tumour Unit
Annals of Surgical Oncology | Year: 2014

Background: Liver transplantation (LT) is performed in selected patients with neuroendocrine hepatic metastases. Survival benefit and the risk of tumor recurrence after LT, also exacerbated by immunosuppressive therapy, remain important clinical issues. Whether patients with particular types of neuroendocrine tumors (NET) benefit more than others is unclear. Methods: Bibliographical searches were performed in PubMed for the terms "liver transplantation and neuroendocrine tumors," "liver transplant and neuroendocrine tumors," "liver transplantation and immunosuppressive therapy," "tumor recurrence." Results: Promising results have been reported for LT for NET metastases with 5-year survival of up to 90 % in patients with well-differentiated gastroenteropancreatic NETs, but only few patients are free of tumor 5 years after LT. Better outcomes have been reported for gastrointestinal tumors than for pancreatic NETs for both survival and risk or recurrence after LT. Selection criteria for LT are limited and include the 2007 Milan Criteria and the 2012 European Neuroendocrine Tumor Society guidelines, including: well-differentiated NET (Ki-67 <10 %), age <55 years, absence of extrahepatic disease, primary tumor removed before transplantation, stable disease for at least 6 months before LT, and <50 % liver involvement. Conclusions: LT might be considered in carefully selected patients. The risk of tumor recurrence remains a significant clinical problem after LT, but data focused on immunosuppression issue are lacking, and there are no currently approved strategies for prevention of recurrence or follow-up protocols. Further studies are needed to define universally accepted inclusion criteria, reliable predictors of better outcome, and optimal timing for LT. © 2014 Society of Surgical Oncology. Source

Khan M.S.,Neuroendocrine Tumour Unit | Khan M.S.,University College London | El-Khouly F.,Neuroendocrine Tumour Unit | Davies P.,Neuroendocrine Tumour Unit | And 2 more authors.
Alimentary Pharmacology and Therapeutics | Year: 2011

Background Somatostatin analogues are the mainstay of therapy for malignant carcinoid syndrome. There is clear evidence that the once monthly intramuscular formulation, Octreotide LAR, controls symptoms of carcinoid syndrome, and recent data also suggests an antitumour effect. There is limited data on prolonged release Lanreotide (Somatuline Autogel, Ipsen Pharma Biotech, Signes, France) and no long-term data to date. Aim To present long-term results of prolonged release Lanreotide in a large cohort of patients with malignant carcinoid syndrome, assessing clinical and objective response and tolerance. Methods Seventy six patients with metastatic midgut neuroendocrine tumours and carcinoid syndrome were included in this 9-year retrospective study. Clinical response was based on symptom score with radiological assessment based on RECIST (Response Evaluation Criteria In Solid Tumours). Results Data were available in 69 patients. Ninety four percent achieved symptomatic response at first follow-up visit. Forty six percent had loss of symptomatic response, but 44% of these achieved control with an increase in dose of prolonged release Lanreotide. Overall, symptoms were well controlled throughout the study period with prolonged release Lanreotide alone in 74% of patients. Twenty six percent required additional treatment despite good initial response. Only 30% demonstrated radiological progression. Eleven patients who were switched from Octreotide LAR had return of symptomatic control. No significant adverse effects were experienced. Conclusions Prolonged release Lanreotide provides good symptomatic control of diarrhoea and flushing as well as tumour stability in patients with malignant carcinoid syndrome. © 2011 Blackwell Publishing Ltd. Source

Mandair D.,Neuroendocrine Tumour Unit | Caplin M.E.,Neuroendocrine Tumour Unit
Best Practice and Research: Clinical Gastroenterology | Year: 2012

Neuroendocrine tumours of the Colon and Rectum are rare but are increasing in incidence as a result of greater investigation with endoscopy and improved histological reporting. Classification with the 2010 WHO TNM staging system as well as grading based on the Ki-67 index has led to improved prognostic assessment. The use of Endoanal Ultrasound has increased the sensitivity of detection of depth of invasion and lymphovascular involvement, which is associated with a poor prognosis. Standard polypectomy has largely been replaced by endoscopic mucosal resection of smaller polyps, although newer techniques such as band ligation or endoscopic submucosal dissection are likely to be associated with less residual disease. The management of advanced disease remains a challenge but new treatments such as Peptide Receptor Targeted therapy and molecular targeted treatments offer hope of improved progression free survival in non-resectable disease. © 2013 Elsevier Ltd. All rights reserved. Source

Karpathakis A.,University College London | Caplin M.,Neuroendocrine Tumour Unit | Thirlwell C.,University College London
Endocrine-Related Cancer | Year: 2012

Neuroendocrine tumours (NETs) are a rare and heterogeneous group of tumours whose incidence is increasing and their prevalence is now greater than that of any other upper gastrointestinal tumour. Diagnosis can be challenging, and up to 25% of patients present with metastatic disease. Following the recent FDA approval of two new molecularly targeted therapies for the treatment of advanced pancreatic NETs (pNETs), the first in 25 years, we review all systemic therapies and suggest where these newer targeted therapies fit in the treatment schedule for these challenging tumours. Clinical trial data relating to the routine use of sunitinib and everolimus in low-intermediate-grade pNETs are summarised alongside newer molecularly targeted agents undergoing clinical assessment in NETs. We particularly focus on the challenge of optimal scheduling of molecularly targeted treatments around existing systemic and localised treatment such as chemotherapy or radiotargeted therapy. We also discuss application of current evidence to subgroups of patients who have not so far been directly addressed such as those with poorer performance status or patients receiving radical surgery who may benefit from adjuvant treatment. © 2012 Society for Endocrinology. Source

Karpathakis A.,University College London | Karpathakis A.,Neuroendocrine Tumour Unit | Dibra H.,University College London | Thirlwell C.,University College London | Thirlwell C.,Neuroendocrine Tumour Unit
Endocrine-Related Cancer | Year: 2013

The field of epigenetics has evolved rapidly over recent years providing insight into the tumorigenesis of many solid and haematological malignancies. Determination of epigenetic modifications in neuroendocrine tumour (NET) development is imperative if we are to improve our understanding of the biology of this heterogenous group of tumours. Epigenetic marks such as DNA methylation at RASSF1A are frequent findings in NETs of all origins and may be associated with worse prognosis. MicroRNA signatures and histone modifications have been identified which can differentiate subtypes of NET and distinguish NET from adenocarcinoma in cases of diagnostic uncertainty. Historically, candidate genedriven approaches have yielded limited insight into the epigenetics of NET. Recent progress has been facilitated by development of high-throughput tools including second-generation sequencing and arrays for analysis of the 'epigenome' of tumour and normal tissue, permitting unbiased approaches such as exome sequencing that identified mutations of chromatin-remodelling genes ATRX/DAXX in 44% of pancreatic NETs. Epigenetic changes are reversible and therefore represent an attractive therapeutic target; to date, clinical outcomes of epigenetic therapies in solid tumours have been disappointing; however, in vitro studies on NETs are promising and further clinical trials are required to determine utility of this class of novel agents. In this review, we perform a comprehensive evaluation of epigenetic changes found in NETs to date, including rare NETs such as phaeochromocytoma and adrenocortical tumours. We suggest priorities for future research and discuss potential clinical applications and novel therapies. Copyright © 2013 Society for Endocrinology. Source

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