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Item does not contain fulltext OBJECTIVE: Pheochromocytomas and paragangliomas (PPGL) are relatively rare and mostly benign tumours. Approximately 10% of PPGL are malignant, as defined by the presence of metastases, i.e chromaffin tissue at a location that usually does not contain chromaffin cells. However, up to 35% of tumours in patients carrying an SDHB mutation appears to be malignant. Nowadays, no reliable marker allows to predict whether a PPGL is, or will become malignant. In addition, there are no curative treatments if metastases occur. The aim of the present study was to dentify genetic markers allowing to distinguish benign from malignant tumours. DESIGN AND METHOD: An mRNA expression array was performed on benign and malignant PPGL. The genes showing a different expression between the benign and malignant tumours were selected to be confirmed and validated by qRT-PCR. Finally, the remaining genes were stained by immunohistochemistry on Tissue MicroArray including a large series of PPGL. RESULTS: Forty benign and 12 malignant PPGL were investigated for differences in mRNA expression with Affymetrix arrays. Expression data were normalized according to Affymetrix recommendations. Then, using Pomelo II (http://pomelo2.bioinfo.cnio.es/), a Limma t-test was performed, to assess which genes were differentially expressed between benign and malignant PPGL. First, a non-clustered analysis was performed and 10 genes with a False Discovery Rate (FDR) below 0.05 and a relative overexpression ratio of at least 4 were found, including Interleukin 13 Receptor alpha 2 (IL13RA2) and Monooxygenase DBH-like 1 (MOXD1). Secondly, a supervised cluster analysis was performed (based on HIF target genes), resulting in 2 groups, which were both investigated for differences in mRNA expression between benign and malignant tumours. Five genes showed an FDR below 0.01 and were overexpressed in malignant tumours with a ratio higher than 4, including Contactin 4 (CNTN4), Iroquois Homeobox 3 (IRX3), and Sulfatase 2 (SULF2). These genes were further investigated using qRT-PCR, and immunohistochemistry on Tissue Micro Array including 91 benign and 12 malignant PPGL. CONCLUSIONS: Significant overexpression of Contactin 4 was shown in malignant compared to benign tumours, and may therefore contribute to distinguish malignant from benign PPGL.

Aim A recent systematic review indicated that dysplasia present before restorative proctocolectomy is a predictor of subsequent dysplasia in the pouch. This prospective study was carried out to assess the prevalence of dysplasia in the ileal pouch in patients having RPC for ulcerative colitis with co-existing dysplasia in the operation specimen. Method Eligible patients were invited for a surveillance endoscopy. The afferent and blind efferent ileal loop, ileoanal pouch and rectal cuff were examined by standard endoscopy using a dye-spray technique with methylene blue. Mucosal abnormalities were biopsied and random biopsies were taken from the afferent and blind ileal loop, pouch and rectal cuff. Results Fourty-four patients (25 male, mean 49 years) underwent pouch endoscopy at a mean interval from RPC of 8.6 years. Dysplasia was detected in two (4.5%) patients. In one, low-grade dysplasia was found in the rectal cuff and in the other low-grade dysplasia was detected in random biopsies from the pouch and the efferent ileal loop. Conclusion This prospective pouch-endoscopy study detected dysplasia in

72-year-old woman with a history of primary hyperparathyroidism, for which she underwent surgery years previously, went to see her general practitioner because of a swelling in her neck that had been present for a few months and was growing in size. Other than this she had no symptoms. During the physical examination a solid elastic, non-fixed swelling with a diameter of about 3 cm was palpable on the right of the neck, medially to the sternocleidomastoid muscle. The swelling did not move when she swallowed. Laboratory tests and an MRI scan were suggestive of parathyroid carcinoma. An examination of the neck showed a large, irregular, lobed soft tumour and several small deposits with a yellowish brown appearance. Histology showed no characteristics of malignancy, but showed a picture consistent with the diagnosis of 'parathyromatosis', a rare disorder characterized by hormonally active ectopic parathyroid tissue. Treatment is primarily surgical, aimed at radical resection. Medicinal therapy using a calcimimetic agent may have a role as an adjuvant treatment

A 53-year-old woman presented with fever accompanied by chills and an extremely painful swelling of her right thyroid lobe. She was initially diagnosed as having subacute thyroiditis, but after 14 days her disease appeared to be caused by a destructive suppurative thyroiditis due to Salmonella group C. A pre-existing hyperplastic nodule in the right thyroid lobe was the predisposing factor. Antibiotics were given for several weeks and surgical drainage was performed. Finally a hemithyroidectomy was done to eliminate the predisposing factor.

A 53-year-old woman presented with fever accompanied by chills and an extremely painful swelling of her right thyroid lobe. She was initially diagnosed as having subacute thyroiditis, but after 14 days her disease appeared to be caused by a destructive suppurative thyroiditis due to Salmonella group C. A pre-existing hyperplastic nodule in the right thyroid lobe was the predisposing factor. Antibiotics were given for several weeks and surgical drainage was performed. Finally a hemithyroidectomy was done to eliminate the predisposing factor.

A 17-year-old boy presented with an atypical manifestation of acute appendicitis. The clinical aspect, radiological investigations and peroperative aspect of the appendix were not conclusive but nevertheless a neuroendocrine tumour (carcinoid tumour) of the appendix was suspected. After ileocaecal resection and resection of pathological lymph nodes, histopathological evaluation revealed the diagnosis: a periappendicular mass without any sign of malignancy. In retrospect, ileocaecal resection was performed for a benign disease. This case illustrates that an unusual presentation of a common disease occurs more frequently than a typical presentation of a rare disease

A 49-year-old woman presented at the emergency ward in shock with upper gastrointestinal bleeding. Extensive ulceration confirmed by gastroduodenoscopy was suggestive of Zollinger-Ellison syndrome. Further evaluation by fasting gastrin assessment, CT, endosonography with cytological biopsy and somatostatin-receptor scintigraphy confirmed the diagnosis ofgastrinoma. Three enlarged lymph nodes near the pancreatic head were surgically removed; each was found to contain neuroendocrine tumour cells. The patient recovered rapidly after surgery and the gastrin level normalised. Zollinger-Ellison syndrome is uncommon but should be considered as a possible cause of upper gastrointestinal bleeding. Shock is very rarely the first sign ofZollinger-Ellison syndrome. In this case, the use of a proton-pump inhibitor may have masked the disease for years

A case of gangliocytic paraganglioma is reported in the appendix which, to the best of our knowledge, is the first case at this particular site to be described in modern literature. A 47-year-old man with signs and symptoms of acute appendicitis underwent appendectomy. In the resected specimen a tumour with a diameter of 9 mm was found, which microscopically consisted of three different cell types: (a) epithelioid cells lying in a trabecular pattern and in formations reminiscent of 'Zellballen' as seen in paragangliomas (b) spindle cells and (c) ganglion-like cells. A diagnosis of 'gangliocytic paraganglioma' was made and confirmed by immunohistochemical and ultrastructural examination. Gangliocytic paragangliomas are rare tumours of uncertain histogenesis. More than 40 years ago a tumour in the appendix with features similar to our case was described by Masson as 'neuro-carcinoïde'. Concerning its origin, Masson, as well as other authors describing gangliocytic paragangliomas decades later, referred to the endodermal-neuroecto dermal complexes found by Van Campenhout. It is felt that the current finding of a gangliocytic paraganglioma in the appendix supports the hypothesis that gangliocytic paragangliomas arise from these embryonal structures

Objective: The aim of this study was to predict recurrence in patients with grade 1 or 2 nonfunctioning pancreatic neuroendocrine tumors (NF-pNET) after curative resection. Background: Surgical resection is the preferred treatment for NF-pNET; however, recurrence occurs frequently after curative surgery, worsening prognosis of patients. Methods: Retrospectively, patients with NF-pNET of 3 institutions were included. Patients with distant metastases, hereditary syndromes, or grade 3 tumors were excluded. Local or distant tumor recurrence was scored. Independent predictors for survival and recurrence were identified using Cox-regression analysis. The recurrence score was developed to predict recurrence within 5 years after curative resection of grade 1 to 2 NF-pNET. Results: With a median follow-up of 51 months, 211 patients with grade 1 to 2 NF-pNET were included. Thirty-five patients (17%) developed recurrence. The 5- and 10-year disease-specific/overall survival was 98%/91% and 84%/68%, respectively. Predictors for recurrence were tumor grade 2, lymph node metastasis, and perineural invasion. On the basis of these predictors, the recurrence score was made. Discrimination [c-statistic 0.81, 95% confidence interval (95% CI) 0.75-0.87] and calibration (Hosmer Lemeshow Chi-square 11.25, P = 0.258) indicated that the ability of the recurrence score to identify patients at risk for recurrence is good. Conclusions: This new scoring system could predict recurrence after curative resection of grade 1 and 2 NF-pNET. With the use of the recurrence score, less extensive follow-up could be proposed for patients with low recurrence risk. For high-risk patients, clinical trials should be initiated to investigate whether adjuvant therapy might be beneficial. External validation is ongoing due to limited availability of adequate cohorts.

Background: Despite evidence of different malignant potentials, postoperative follow-up assessment is similar for G1 and G2 pancreatic neuroendocrine tumors (panNETs) and adjuvant treatment currently is not indicated. This study investigated the role of Ki67 with regard to recurrence and survival after curative resection of panNET. Methods: Patients with resected non-functioning panNET diagnosed between 1992 and 2016 from three institutions were retrospectively analyzed. Patients who had G1 or G2 tumor without distant metastases or hereditary syndromes were included in the study. The patients were re-categorized into Ki67 0–5 and Ki67 6–20%. Cox regression analysis with log-rank testing for recurrence and survival was performed. Results: The study enrolled 241 patients (86%) with Ki67 0–5% and 39 patients (14%) with Ki67 6–20%. Recurrence was seen in 34 patients (14%) with Ki67 0–5% after a median period of 34months and in 16 patients (41%) with Ki67 6–20% after a median period of 16months (p < 0.001). The 5-year recurrence-free and 10-year disease-specific survival periods were respectively 90 and 91% for Ki67 0–5% and respectively 55 and 26% for Ki67 6–20% (p < 0.001). The overall survival period after recurrence was 44.9months, which was comparable between the two groups (p = 0.283). In addition to a Ki67 rate higher than 5%, tumor larger than 4cm and lymph node metastases were independently associated with recurrence. Conclusions: Patients at high risk for recurrence after curative resection of G1 or G2 panNET can be identified by a Ki67 rate higher than 5%. These patients should be more closely monitored postoperatively to detect recurrence early and might benefit from adjuvant treatment. A clear postoperative follow-up regimen is proposed.