An increased interest in gastro-entero-pancreatic neuroendocrine neoplasms (GEP NENs) has recently been observed. These are rare neoplasms and their detection in recent years has improved. Over 50% of GEP NENs are carcinoids, and they are usually found incidentally during surgery in the small intestine and appendix and at diagnosis in distant metastases, mainly to the liver. There is a need for co-operation between specialists in various disciplines of medicine in order to work out the diagnostic and therapeutic guidelines. In this publication, we present general recommendations of the Polish Network of Neuroendocrine Tumours for the management of patients with GEP NENs, developed at the Consensus Conference which took place in Kamień Śląski in April 2013. Members of the guidelines working groups were assigned sections of the 2008 guidance to update. In the subsequent parts of this publication, we present the rules of diagnostic and therapeutic management of: -neuroendocrine neoplasms of the stomach and duodenum (including gastrinoma); -pancreatic neuroendocrine neoplasms; -neuroendocrine neoplasms of the small intestine and the appendix; -colorectal neuroendocrine neoplasms. The proposed recommendations by Polish and foreign experts representing different fields of medicine (endocrinology, gastroenterology, surgery, oncology, nuclear medicine and pathology) will be helpful in the diagnosis and treatment of GEP NENs patients.

PurposeThe objective of this article is to present a new method for the diagnosis of insulinoma with the use of [Lys40(Ahx-HYNIC-99mTc/EDDA)NH2]-exendin-4.MethodsStudies were performed in 11 patients with negative results of all available non-isotopic diagnostic methods (8 with symptoms of insulinoma, 2 with malignant insulinoma and 1 with nesidioblastosis). In all patients glucagon-like peptide-1 (GLP-1) receptor imaging (whole-body and single photon emission computed tomography/CT examinations) after the injection of 740 MBq of the tracer was performed.ResultsBoth sensitivity and specificity of GLP-1 receptor imaging were assessed to be 100 % in patients with benign insulinoma. In all eight cases with suspicion of insulinoma a focal uptake in the pancreas was found. In six patients surgical excision of the tumour was performed (type G1 tumours were confirmed histopathologically). In one patient surgical treatment is planned. One patient was disqualified from surgery. In one case with malignant insulinoma pathological accumulation of the tracer was found only in the region of local recurrence. The GLP-1 study was negative in the other malignant insulinoma patient. In one case with suspicion of nesidioblastosis, a focal accumulation of the tracer was observed and histopathology revealed coexistence of insulinoma and nesidioblastosis.Conclusion[Lys40(Ahx-HYNIC-99mTc/EDDA)NH2]-exendin-4 seems to be a promising diagnostic tool in the localization of small insulinoma tumours, but requires verification in a larger series of patients.

Mutations in the cell cycle checkpoint kinase 2 (CHEK2) tumor suppressor gene are associated with multi-organ cancer susceptibility including cancers of the breast and prostate. A genetic association between thyroid and breast cancer has been suggested, however little is known about the determinants of this association. To characterize the association of CHEK2 mutations with thyroid cancer, we genotyped 468 unselected patients with papillary thyroid cancer and 468 (matched) cancer-free controls for four founder mutations of CHEK2 (1100delC, IVS2 1 1G>A, del5395 and I157T). We compared the family histories reported by patients with a CHEK2 mutation to those of non-carriers. A CHEK2 mutation was seen in 73 of 468 (15.6%) unselected patients with papillary thyroid cancer, compared to 28 of 460 (6.0%) age-and sex-matched controls (OR 3.3; p < 0.0001). A truncating mutation (IVS2 1 1G>A, 1100delC or del5395) was associated with a higher risk of thyroid cancer (OR 5 5.7; p 5 0.006), than was the missense mutation I157T (OR 5 2.8; p 5 0.0001). CHEK2 mutation carriers reported a family history of breast cancer 2.2 times more commonly than non-carriers (16.4% vs.8.1%; p 5 0.05). A CHEK2 mutation was found in seven of 11 women (63%) with multiple primary cancers of the breast and thyroid (OR 5 10; p 5 0.0004). These results suggest that CHEK2 mutations predispose to thyroid cancer, familial aggregations of breast and thyroid cancer and to double primary cancers of the breast and thyroid.Thyroid cancer is one of the most common cancers in young women. 1 The most common type of thyroid cancer is papillary thyroid cancer, which comprises 80% of all thyroid tumors. 2 Approximately 5% of cases of papillary thyroid cancer are familial. 3 Epidemiologic data suggests that inherited factors contribute to papillary thyroid cancer. 4 A familial association between thyroid and breast cancer has been suggested; a prior history of thyroid cancer is a risk factor for breast cancer and vice versa (relative risks in the range of 1.7-12.4). 5-11 However, outside of a rare inherited syndrome of cancer susceptibility called Cowden syndrome (caused by PTEN mutations) in which both breast and thyroid cancer risks are increased, the genetic basis for the association between these two cancers has not been established. 12 Cell cycle checkpoint kinase 2 (CHEK2) is a key component of the DNA damage pathway. [13][14][15][16] Four founder alleles of CHEK2 are present in Poland, three of these result in a truncated CHEK2 protein (c.1100delC, c.444 1 1G>A, del5395) and the fourth (c.470T>C) is a missense substitution of an isoleucine for a threonine in exon 3. 17 All these alleles were associated with multi-organ cancer susceptibility, including cancers of the breast and thyroid. [18][19][20] In the current study, we wished to better characterize the association between CHEK2 mutations and thyroid cancer. We genotyped 468 unselected patients with papillary thyroid cancer and 468 matched cancer-free controls for four founder mutations of CHEK2. We also ...

Summary Context An activating mutation in the gene BRAF has been correlated with poorer prognosis and more aggressive clinical course in papillary thyroid carcinoma (PTC). We therefore hypothesized that the good prognosis, high 5‐year disease‐free rate and high survival rate of patients with less aggressive papillary thyroid microcarcinoma (pT1aNo‐x) would be associated with a lower incidence of the BRAFV600E mutation. Objectives To evaluate the frequency of the activating mutation BRAFV600E in low‐risk papillary thyroid microcarcinoma (pT1aNo‐x at the moment of diagnosis) and the association of the mutation with the clinical outcome in a retrospective analysis. Study Design BRAFV600E was characterized in 113 PTC patients diagnosed with pT1aNo‐x (one PTC focus with a diameter <1 cm, without lymph node or distant metastases according to IUCC/AJCC TNM staging system 2010). Genotyping was performed on DNA extracted from thyroid tumour tissue using direct capillary sequencing, and allele‐specific amplification PCR was used to resolve equivocal results. Retrospective analysis of the clinical course of PTC was then correlated with BRAF status in the primary tumour tissue. Results The BRAFV600E mutation was detected in 78 of the 113 pT1aNo‐x patients (69·0%). We observed no persistence, locoregional recurrence, lymph node or distant metastases or deaths in the study group during the 12‐year study (January 2001 to December 2012). Conclusions The presence of the activating BRAFV600E mutation in a significant percentage of papillary thyroid microcarcinoma indicates that further analyses are required to verify its usefulness as a predictor of clinical outcome in PTC. In this study, there was no correlation between BRAF‐positive primary focus of papillary microcarcinoma and more aggressive or recurrent disease.

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