Midgut neuroendocrine tumours with liver metastases: results of the UKINETS study

Ahmed, Alia; Turner, G. Grey; King, Barbara; Jones, Louise; Culliford, David; McCance, David R.; Ardill, Joy; Johnston, Brian T.; Poston, Graeme J.; Rees, Myrddin; Buxton-Thomas, M.; Caplin, Martyn; Ramage, John

doi:10.1677/erc-09-0042

Cited by 251 publications

(242 citation statements)

References 39 publications

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“…In European and American referral centers, up to 77 and 91 % of patients with PNETs and intestinal NETs [19][20][21][22] present with distant metastases at initial diagnosis, respectively [13]. In the present Japanese study, patients in whom distant metastases were observed at initial diagnosis accounted for 19.9 % of PNETs and 6.0 % of GI-NETs.…”

Section: Discussionmentioning

confidence: 46%

Epidemiological trends of pancreatic and gastrointestinal neuroendocrine tumors in Japan: a nationwide survey analysis

et al. 2014

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Background Although neuroendocrine tumors (NETs) are rare, the number of patients with NET is increasing. However, in Japan, there have been no epidemiological studies on NET since 2005; thus, the prevalence of NET remains unknown. Methods We reported the epidemiology of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) [pancreatic neuroendocrine tumors (PNETs) and gastrointestinal neuroendocrine tumors (GI-NETs)] in Japan in 2005. Here, we conducted the second nationwide survey on patients with GEP-NETs who received treatment in 2010. Results A total of 3,379 patients received treatment for PNETs in 2010, representing a 1.2-fold increase in the number of patients from 2005 to 2010. The prevalence was estimated to be 2.69/100,000, with an annual onset incidence of 1.27/100,000 in 2010. Non-functioning tumor (NF)-PNETs comprised 65.5 % of cases followed by insulinoma (20.9 %) and gastrinoma (8.2 %). Interestingly, the number of patients with NF-PNETs increased *1.8 fold since 2005. A total of 19.9 % of patients exhibited distant metastasis at initial diagnosis; 4.3 % had complications with multiple endocrine neoplasia type 1 (MEN-1), and only 4.0 % had NF-PNETs associated with MEN-1. Meanwhile, an estimated 8,088 patients received treatment for GI-NETs, representing a *1.8-fold increase since 2005. The prevalence was estimated to be 6.42/100,000, with an annual onset incidence of 3.51/100,000. The locations of GI-NETs varied: foregut, 26.1 %; midgut, 3.6 %; and hindgut, 70.3 %. Distant metastasis and complications with MEN-1 were observed in 6.0 and 0.42 % at initial diagnosis, respectively. The frequency of carcinoid syndrome in patients with GI-NETs was 3.2 %. Conclusion We clarified the epidemiological changes in GEP-NETs from 2005 to 2010 in Japan.

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Section: Discussionmentioning

confidence: 46%

Epidemiological trends of pancreatic and gastrointestinal neuroendocrine tumors in Japan: a nationwide survey analysis

et al. 2014

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“…Secondly, in patients with unresectable liver metastases it has the palliative aim of avoiding local complications, such as obstruction and bleeding. Finally, even when curative resection of liver metastases is no longer a possibility, the resection of primary tumors (mesenteric lymph node metastases included) may still provide substantial survival benefit [4,5,[14][15][16]. However, strong evidences supporting this approach are lacking and the ENETS Consensus Guidelines suggest caution: an interdisciplinary team should evaluate patients that fit for surgery with unresectable liver metastases [17].…”

Section: Discussionmentioning

confidence: 99%

“…Particularly, localization of mid-gut tumors might be challenging due to their usually small size. In these patients, resection of the primary lesion is a palliative treatment that could reduce local complications and might even increase survival [4,5]. Therefore, a multimodality imaging approach including computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), somatostatin receptor scintigraphy (SSRS) and endoscopy is often necessary for detecting the primary tumor [6].…”

Section: Introductionmentioning

confidence: 99%

The Role of Wireless Capsule Endoscopy (WCE) in the Detection of Occult Primary Neuroendocrine Tumors

Furnari

Buda²,

Delconte

et al. 2017

JGLD

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Background & Aims: Neuroendocrine tumors (NETs) are a heterogeneous group of neoplasms with unclear etiology that may show functioning or non-functioning features. Primary tumor localization often requires integrated imaging. The European Neuroendocrine Tumors Society (ENETS) guidelines proposed wireless-capsule endoscopy (WCE) as a possible diagnostic tool for NETs, if intestinal origin is suspected. However, its impact on therapeutic management is debated. We aimed to evaluate the yield of WCE in detecting intestinal primary tumor in patients showing liver NET metastases when first-line investigations are inconclusive.Method: Twenty-four patients with histological diagnosis of metastatic NET from liver biopsy and no evidence of primary lesions at first-line investigations were prospectively studied in an ENETS-certified tertiary care center. Wireless-capsule endoscopy was requested before explorative laparotomy and intra-operative ultrasound. The diagnostic yield of WCE was compared to the surgical exploration.Results: Sixteen subjects underwent surgery; 11/16 had positive WCE identifying 16 bulging lesions. Mini-laparotomy found 13 NETs in 11/16 patients (9 small bowel, 3 pancreas, 1 bile ducts). Agreement between WCE and laparotomy was recorded in 9 patients (Sensitivity=75%; Specificity=37.5%; PPV=55%; NPV=60%). Correspondence assessed per-lesions produced similar results (Sensitivity=70%; Specificity=25%; PPV=44%; NPV=50%). No capsule retentions were recorded.Conclusions: Wireless-capsule endoscopy is not indicated as second-line investigation for patients with gastro-entero-pancreatic NETs. In the setting of a referral center, it might provide additional information when conventional investigations are inconclusive about the primary site.Abbreviations: DBE: double balloon enteroscopy; GEP-NET: gastro-entero-pancreatic neuroendocrine tumor; GI: gastrointestinal; ENETS: European Neuroendocrine Tumor Society; NET: neuroendocrine tumor; SSRS: somatostatin receptor scintigraphy; WCE: wireless capsule endoscopy.

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“…These intriguing characteristics contribute to a 5-year survival of less than 60% from diagnosis of liver metastases (Ahmed et al 2009) compared to about 80% in patients with loco-regionally limited disease (Norlén et al 2012). The lack of specific and sensitive biomarkers to stratify NETs according to subtype, determine tumour burden, assess disease progression, select patients for individualised treatment and monitor treatment efficacy is a key issue in management of NETs (Modlin et al 2008.…”

Section: Introductionmentioning

confidence: 99%

MicroRNAs associated with small bowel neuroendocrine tumours and their metastases

Miller¹,

Frampton²,

Malczewska³

et al. 2016

Endocrine-Related Cancer

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Novel molecular analytes are needed in small bowel neuroendocrine tumours (SBNETs) to better determine disease aggressiveness and predict treatment response. In this study, we aimed to profile the global miRNome of SBNETs, and identify microRNAs (miRNAs) involved in tumour progression for use as potential biomarkers. Two independent miRNA profiling experiments were performed (n = 90), including primary SBNETs (n = 28), adjacent normal small bowel (NSB; n = 14), matched lymph node (LN) metastases (n = 24), normal LNs (n = 7), normal liver (n = 2) and liver metastases (n = 15). We then evaluated potentially targeted genes by performing integrated computational analyses. We discovered 39 miRNAs significantly deregulated in SBNETs compared with adjacent NSB. The most upregulated (miR-204-5p, miR-7-5p and miR-375) were confirmed by qRT-PCR. Two miRNAs (miR-1 and miR-143-3p) were significantly downregulated in LN and liver metastases compared with primary tumours. Furthermore, we identified upregulated gene targets for miR-1 and miR-143-3p in an existing SBNET dataset, which could contribute to disease progression, and show that these miRNAs directly regulate FOSB and NUAK2 oncogenes. Our study represents the largest global miRNA profiling of SBNETs using matched primary tumour and metastatic samples. We revealed novel miRNAs deregulated during SBNET disease progression, and important miRNA-mRNA interactions. These miRNAs have the potential to act as biomarkers for patient stratification and may also be able to guide treatment decisions. Further experiments to define molecular mechanisms and validate these miRNAs in larger tissue cohorts and in biofluids are now warranted.

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Midgut neuroendocrine tumours with liver metastases: results of the UKINETS study

Cited by 251 publications

References 39 publications

Epidemiological trends of pancreatic and gastrointestinal neuroendocrine tumors in Japan: a nationwide survey analysis

Epidemiological trends of pancreatic and gastrointestinal neuroendocrine tumors in Japan: a nationwide survey analysis

The Role of Wireless Capsule Endoscopy (WCE) in the Detection of Occult Primary Neuroendocrine Tumors

MicroRNAs associated with small bowel neuroendocrine tumours and their metastases

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