Tumour size is not a reliable criterion for management of patients with Non-secreting pancreatic neuroendocrine tumours: results of a large, multi-centre, operative cohort

ObjectiveRecent studies have found aristaless-related homeobox gene (ARX)/pancreatic and duodenal homeobox 1 (PDX1), alpha-thalassemia/mental retardation X-linked (ATRX)/death domain-associated protein (DAXX) and alternative lengthening of telomeres (ALT) to be promising prognostic biomarkers for non-functional pancreatic neuroendocrine tumours (NF-PanNETs). However, they have not been comprehensively evaluated, especially among small NF-PanNETs (≤2.0 cm). Moreover, their status in neuroendocrine tumours (NETs) from other sites remains unknown.DesignAn international cohort of 1322 NETs was evaluated by immunolabelling for ARX/PDX1 and ATRX/DAXX, and telomere-specific fluorescence in situ hybridisation for ALT. This cohort included 561 primary NF-PanNETs, 107 NF-PanNET metastases and 654 primary, non-pancreatic non-functional NETs and NET metastases. The results were correlated with numerous clinicopathological features including relapse-free survival (RFS).ResultsATRX/DAXX loss and ALT were associated with several adverse prognostic findings and distant metastasis/recurrence (p<0.001). The 5-year RFS rates for patients with ATRX/DAXX-negative and ALT-positive NF-PanNETs were 40% and 42% as compared with 85% and 86% for wild-type NF-PanNETs (p<0.001 and p<0.001). Shorter 5-year RFS rates for ≤2.0 cm NF-PanNETs patients were also seen with ATRX/DAXX loss (65% vs 92%, p=0.003) and ALT (60% vs 93%, p<0.001). By multivariate analysis, ATRX/DAXX and ALT status were independent prognostic factors for RFS. Conversely, classifying NF-PanNETs by ARX/PDX1 expression did not independently correlate with RFS. Except for 4% of pulmonary carcinoids, ATRX/DAXX loss and ALT were only identified in primary (25% and 29%) and NF-PanNET metastases (62% and 71%).ConclusionsATRX/DAXX and ALT should be considered in the prognostic evaluation of NF-PanNETs including ≤2.0 cm tumours, and are highly specific for pancreatic origin among NET metastases of unknown primary.

Download Full-text

Serotonin-Secreting Neuroendocrine Tumours of the Pancreas

Journal of Clinical Medicine ◽

10.3390/jcm9051363 ◽

2020 ◽

Vol 9 (5) ◽

pp. 1363

Author(s):

Anna Caterina Milanetto ◽

Matteo Fassan ◽

Alina David ◽

Claudio Pasquali

Keyword(s):

Liver Metastases ◽

Carcinoid Syndrome ◽

Neuroendocrine Tumours ◽

Tumour Size ◽

Somatostatin Analogues ◽

High Serum ◽

Resective Surgery ◽

Alive With Disease ◽

Pancreatic Neuroendocrine Tumours ◽

Well Differentiated

Background: Serotonin-secreting pancreatic neuroendocrine tumours (5-HT-secreting pNETs) are very rare, and characterised by high urinary 5-hydroxyindole-acetic acid (5-HIAA) levels (or high serum 5-HT levels). Methods: Patients with 5-HT-secreting pancreatic neoplasms observed in our unit (1986–2015) were included. Diagnosis was based on urinary 5-HIAA or serum 5-HT levels. Results: Seven patients were enrolled (4 M/3 F), with a median age of 64 (range 38–69) years. Two patients had a carcinoid syndrome. Serum 5-HT was elevated in four patients. Urinary 5-HIAA levels were positive in six patients. The median tumour size was 4.0 (range 2.5–10) cm. All patients showed liver metastases at diagnosis. None underwent resective surgery; lymph node/liver biopsies were taken. Six lesions were well-differentiated tumours and one a poorly differentiated carcinoma (Ki67 range 3.4–70%). All but one patient received chemotherapy. Four patients received somatostatin analogues; three patients underwent ablation of liver metastases. One patient is alive with disease 117 months after observation. All the others died from disease progression after a follow-up within 158 months. Conclusions: Primary 5-HT-secreting pNETs are mostly metastatic to the liver; patients are not amenable to resective surgery. Despite high 5-HIAA urinary levels, few patients present with carcinoid syndrome. A five-year survival rate of 42.9% may be achieved with multimodal treatment.

Download Full-text

Impact of tumour size on metastasis and survival in patients with pancreatic neuroendocrine tumours (PNETs): A population based study

Journal of Cancer ◽

10.7150/jca.27779 ◽

2019 ◽

Vol 10 (25) ◽

pp. 6349-6357

Author(s):

Yangyang Liu ◽

Shufang Ye ◽

Yabi Zhu ◽

Xingkang He ◽

Jie Pan ◽

...

Keyword(s):

Neuroendocrine Tumours ◽

Tumour Size ◽

Population Based ◽

Population Based Study ◽

Pancreatic Neuroendocrine Tumours

Download Full-text

Management of multiple endocrine neoplasia type 1 (MEN1) and sporadic pancreatic neuroendocrine tumours (PNETS) in relation to the clinical guidelines: a single centre audit

Endocrine Abstracts ◽

10.1530/endoabs.44.p78 ◽

2016 ◽

Author(s):

Georgia Ntali ◽

Paul J Newey ◽

Victoria Stokes ◽

Denis Talbot ◽

Zahir Soonawalla ◽

...

Keyword(s):

Clinical Guidelines ◽

Multiple Endocrine Neoplasia ◽

Neuroendocrine Tumours ◽

Multiple Endocrine Neoplasia Type ◽

Single Centre ◽

Endocrine Neoplasia ◽

Endocrine Neoplasia Type ◽

Pancreatic Neuroendocrine Tumours

Download Full-text

Algorithm of diagnosis of pancreatic neuroendocrine tumours on fine needle aspiration specimens

10.26226/morressier.5b4709846f4cb3001095179a ◽

2018 ◽

Author(s):

Cristiana Popp ◽

Mirela Daiela Cioplea ◽

Sabina Zurac ◽

Patricia-Irina Stinga ◽

Alexandra Ioana Dragusin ◽

...

Keyword(s):

Fine Needle Aspiration ◽

Neuroendocrine Tumours ◽

Needle Aspiration ◽

Fine Needle ◽

Pancreatic Neuroendocrine Tumours

Download Full-text

Faculty Opinions recommendation of Laparoscopic versus open pancreas resection for pancreatic neuroendocrine tumours: a systematic review and meta-analysis.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.727348091.793531197 ◽

2017 ◽

Author(s):

Christos Dervenis ◽

Dionysia Kelgiorgi

Keyword(s):

Systematic Review ◽

Neuroendocrine Tumours ◽

Meta Analysis ◽

Pancreas Resection ◽

Pancreatic Neuroendocrine Tumours

Download Full-text

Imaging of Pancreatic-Neuroendocrine Tumours: An Outline of Conventional Radiological Techniques

Current Radiopharmaceuticals ◽

10.2174/1874471012666190214165845 ◽

2019 ◽

Vol 12 (2) ◽

pp. 135-155 ◽

Cited By ~ 2

Author(s):

Muhammad Affan Zamir ◽

Wasim Hakim ◽

Siraj Yusuf ◽

Robert Thomas

Keyword(s):

Neuroendocrine Tumours ◽

Treatment Options ◽

Advantages And Disadvantages ◽

Imaging Characteristics ◽

Fundamental Understanding ◽

Pancreatic Neuroendocrine Tumours ◽

Direct Management ◽

Important Disease ◽

Similar Imaging

IIntroduction: Pancreatic Neuroendocrine Tumours (p-NETs) are an important disease entity and comprise of peptide-secreting tumours often with a functional syndrome. : Accounting for a small percentage of all pancreatic tumours, they have a good overall survival rate when diagnosed early, with surgery being curative. The role of nuclear medicine in the diagnosis and treatment of these tumours is evident. However, the vast majority of patients will require extensive imaging in the form of conventional radiological techniques. It is important for clinicians to have a fundamental understanding of the p-NET appearances to aid prompt identification and to help direct management through neoplastic staging. Methods: This article will review the advantages and disadvantages of conventional radiological techniques in the context of p-NETs and highlight features that these tumours exhibit. Conclusion: Pancreatic neuroendocrine tumours are a unique collection of neoplasms that have markedly disparate clinical features but similar imaging characteristics. Most p-NETs are small and welldefined with homogenous enhancement following contrast administration, although larger and less welldifferentiated tumours can demonstrate areas of necrosis and cystic architecture with heterogeneous enhancement characteristics. : Prognosis is generally favourable for these tumours with various treatment options available. However, conventional radiological techniques will remain the foundation for the initial diagnosis and staging of these tumours, and a grasp of these modalities is extremely important for physicians.

Download Full-text

Peptide Receptor Radionuclide Therapy for Pancreatic Neuroendocrine Tumours

Current Radiopharmaceuticals ◽

10.2174/1874471012666190201164132 ◽

2019 ◽

Vol 12 (2) ◽

pp. 126-134 ◽

Cited By ~ 5

Author(s):

Shahad Alsadik ◽

Siraj Yusuf ◽

Adil AL-Nahhas

Keyword(s):

Side Effects ◽

Effective Treatment ◽

Radionuclide Therapy ◽

Neuroendocrine Tumours ◽

Peptide Receptor Radionuclide Therapy ◽

Progression Free Survival ◽

Treatment Modalities ◽

Effective Treatment Option ◽

Peptide Receptor ◽

Pancreatic Neuroendocrine Tumours

Background: The incidence of pancreatic Neuroendocrine Tumours (pNETs) has increased considerably in the last few decades. The characteristic features of this tumour and the development of new investigative and therapeutic methods had a great impact on its management. Objective: The aim of this review is to investigate the outcome of Peptide Receptor Radionuclide Therapy (PRRT) in the treatment of pancreatic neuroendocrine tumours. Methods: A comprehensive literature search strategy was used based on two databases (SCOPUS, and PubMed). We considered all studies published in English, evaluating the use of PRRT (177Luteciuim- DOTA-conjugated peptides and 90Yetrium- DOTA- conjugated peptides) in the treatment of pancreatic neuroendocrine tumours as a standalone entity or as a subgroup within the wider category of Gastroenteropancreatic Neuroendocrine Tumours (GEP NETs). Results: PRRT was found to be an effective treatment modality as a monotherapy or in combination with other therapies in the treatment of non-operable and metastatic pNETs where other options are limited. Complete response was reported to be between 2-6% while partial response was achieved in up to 60% of cases. Survival analysis was also impressive. Progression Free Survival (PFS) reached a mean of 34 months and Overall Survival (OS) of 53 months. PRRT also proved to improve patients’ Quality of Life (QoL). Acute and sub-acute side effects like nephrotoxicity and haematotoxicity are usually mild and reversible. Conclusion: PRRT is well tolerated and effective treatment option for non-operable and/or metastatic pNETs. Side effects are usually mild and reversible. Larger randomized controlled trails need to be done to compare PRRT with other treatment modalities and to provide more detailed guidelines regarding patient selections, the choice of PRRT, follow up and response assessment to maximum potential benefit.

Download Full-text