Surgical Management of Primary Small Bowel NET Presenting Acutely with Obstruction or Perforation.

Up to 35% of small bowel neuroendocrine tumors (SBNETs) may present with an acute intra-abdominal complication including obstruction, perforation, bleeding or ischemia and may require emergency surgical treatment in centers not normally accustomed to managing patients with neuroendocrine tumors. These patients may have a known diagnosis of SBNET, be suspected as suffering from SBNET or have SBNET diagnosed as an incidental finding on presenting radiology or postoperative pathology. Perioperative priorities include obtaining both clinical and radiological staging with cross-sectional imaging and clinical examination, screening for the presence of carcinoid syndrome and right-sided cardiac disease and assessment of prognosis. Intraoperatively careful attention should be paid to noting the presence and location of multifocal primary and metastatic disease. Ideally, surgical resection with mesenteric lymph node dissection is the treatment of choice for obstructing and perforating lesions. Extended lymphadenectomy along the SMA, SMV and behind the pancreas should be primarily considered an elective procedure. In unwell patients with advanced disease surgical bypass (jejuno or ileocolic) or proximal defunctioning should be undertaken but, given the excellent long-term survivals in patients with stage IV disease, could be considered bridging procedures to elective resection following formal staging and multidisciplinary review.

The safety of anaesthetising biochemically hyperthyroid patients undergoing thyroidectomy-a retrospective cohort study.

Traditionally it is recommended that hyperthyroid patients should be made euthyroid prior to thyroidectomy. However, several small observational studies have reported no increase in adverse events when hyperthyroid patients undergo thyroidectomy. The aim of this study was to assess outcomes following total thyroidectomy in patients who were biochemically hyperthyroid at the time of surgery compared to those who were euthyroid. One hundred and fifty-one eligible patients undergoing thyroidectomy for hyperthyroidism between January 2012 and February 2016 were identified, of whom 57 were hyperthyroid on perioperative blood tests and 94 were euthyroid (comparison group). Primary outcomes were 30-day mortality, increased length of postoperative hospital stay and intraoperative signs consistent with thyrotoxicosis (e.g. heart rate >100 per minute, systolic blood pressure >180 or <60 mmHg, or temperature >38°C). Secondary outcomes were intraoperative beta-blocker use and level of care required postoperatively. Thirty-day mortality was zero. The only significant difference between the two groups was a higher use of intraoperative beta-blockers amongst hyperthyroid patients (28.1% versus 8.5%, P=0.002). Our findings suggest that thyroidectomy for mild to moderate biochemical hyperthyroidism performed by an experienced thyroid surgeon and anaesthetist, is associated with increased intraoperative beta-blocker use but no statistical difference in mortality, length of postoperative stay or intraoperative signs consistent with thyrotoxicosis. While we still recommend attempting to achieve a euthyroid state whenever possible prior to thyroid surgery, mild to moderate degrees of residual biochemical hyperthyroidism when appropriately managed may not be associated with an increase in adverse outcomes.

Overexpression of miR-210 is associated with SDH-related pheochromocytomas, paragangliomas, and gastrointestinal stromal tumours.

miR-210 is a key regulator of response to hypoxia. Pheochromocytomas (PCs) and paragangliomas (PGLs) with germline SDHx or VHL mutations have pseudohypoxic gene expression signatures. We hypothesised that PC/PGLs containing SDHx or VHL mutations, and succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumours (GISTs), would overexpress miR-210 relative to non-SDH or -VHL-mutated counterparts. miR-210 was analysed by quantitative PCR in i) 39 PC/PGLs, according to genotype (one SDHA, five SDHB, seven VHL, three NF1, seven RET, 15 sporadic, one unknown) and pathology (18 benign, eight atypical, 11 malignant, two unknown); ii) 18 GISTs, according to SDHB immunoreactivity (nine SDH-deficient and nine SDH-proficient) and iii) two novel SDHB-mutant neurosphere cell lines. miR-210 was higher in SDHx- or VHL-mutated PC/PGLs (7.6-fold) compared with tumours without SDHx or VHL mutations (P=0.0016). miR-210 was higher in malignant than in unequivocally benign PC/PGLs (P=0.05), but significance was lost when benign and atypical tumours were combined (P=0.08). In multivariate analysis, elevated miR-210 was significantly associated with SDHx or VHL mutation, but not with malignancy. In GISTs, miR-210 was higher in SDH-deficient (median 2.58) compared with SDH-proficient tumours (median 0.60; P=0.0078). miR-210 was higher in patient-derived neurosphere cell lines containing SDHB mutations (6.5-fold increase) compared with normal controls, in normoxic conditions (P<0.01). Furthermore, siRNA-knockdown of SDHB in HEK293 cells increased miR-210 by 2.7-fold (P=0.001) under normoxia. Overall, our results suggest that SDH deficiency in PC, PGL and GISTs induces miR-210 expression and substantiates the role of aberrant hypoxic-type cellular responses in the development of these tumours.

Duration of cortisol suppression following a single dose of dexamethasone in healthy volunteers: a randomised double-blind placebo-controlled trial.

The synthetic glucocorticoid dexamethasone is administered to many patients receiving a general anaesthetic to reduce the risk of postoperative nausea and vomiting. Dexamethasone is known to suppress the hypothalamic-pituitary-adrenal axis; however, the duration of this suppression following the standard anti-emetic intravenous dose of 4 to 8 mg used with anaesthesia is unknown. A randomised controlled double-blind crossover trial assessing the effects of 8 mg intravenous dexamethasone versus saline control was performed in ten healthy male volunteers. The adrenal, thyroid and gonadal axes and glucose levels were assessed over a four-day period after dexamethasone administration. All participants had normal baseline hypothalamic-pituitary-adrenal axis function. No difference in cortisol levels was demonstrated at four or eight hours after dexamethasone administration compared with placebo. At 24 hours post dexamethasone, the cortisol had dropped to less than 5% of baseline and returned to normal during the subsequent day. Increased plasma glucose levels were also observed in the dexamethasone group as compared with placebo. A dose of 8 mg of dexamethasone results in significant suppression of the hypothalamic-pituitary-adrenal axis and elevated plasma glucose levels. The cortisol suppression is maximal at approximately 24 hours post dose.

Novel mutation in the TMEM127 gene associated with phaeochromocytoma.

Phaeochromocytomas and paragangliomas are rare neuroendocrine tumours that arise from the adrenal glands or paraganglia (paragangliomas) within the abdomen, thorax and neck. Although it was originally suggested that approximately 10% of these tumours were inherited, it is now recognised that up to approximately 30% of these tumours are associated with a germline mutation in one of the phaeochromocytoma/paraganglioma susceptibility genes. Of the 12 currently known genes predisposing to these tumours, the TMEM127 gene is one of the more recently identified and appears to be present in approximately 2% of apparently sporadic phaeochromocytomas. We report a 33-year-old man who presented with an apparently sporadic adrenal phaeochromocytoma and was identified as carrying a novel TMEM127 germline mutation, p.Gln139X. Patients harbouring a germline TMEM127 mutation most commonly present with an apparently sporadic solitary adrenal phaeochromocytoma. Testing patients who present with a phaeochromocytoma or paraganglioma for an underlying germline mutation needs to be considered in all patients due to implications for family members, but a strategy based on clinical and immunohistochemical findings would be prudent to limit costs.

Patients with RET D631Y mutations most commonly present with pheochromocytoma and not medullary thyroid carcinoma.

Multiple endocrine neoplasia type 2a results from an activating germline mutation in the RET proto-oncogene. Carriers of a RET mutation are at risk of medullary thyroid carcinoma, pheochromocytoma, and primary hyperparathyroidism. Most individuals with multiple endocrine neoplasia type 2a eventually develop medullary thyroid carcinoma and as there is a strong genotype-phenotype correlation, guidelines have been established as to the age recommended for prophylactic thyroidectomy. However for rare mutations in the RET proto-oncogene there is insufficient evidence to provide guidance as to the risk of medullary thyroid carcinoma. We present a family with the rare RET mutation, D631Y in which the proband initially presented with a pheochromocytoma, and review the available literature pertaining to this mutation. In 83% of index cases, pheochromocytoma was the presenting feature and only 37% of adult germline mutation carriers have developed medullary thyroid carcinoma, none of whom have been reported to have nodal or metastatic disease. Patients with a D631Y RET mutation typically present with pheochromocytoma and medullary thyroid carcinoma appears to occur with a later onset than reported with other RET mutations. Based on the current literature we recommend performing prophylactic total thyroidectomy by age 12 years for D631Y carriers although this recommendation may need to be reviewed as additional data becomes available.

Surgical trends in the management of thyroid lymphoma.

AIMS: To determine the changing trends and current role of surgery for the management of thyroid lymphoma. METHODS: A retrospective review of 50 surgical patients with a final diagnosis of thyroid lymphoma over a 35-year period. RESULTS: All patients presented with an enlarging mass, with half having compressive symptoms on presentation. Two-thirds of patients had co-existent histological features of Hashimoto's thyroiditis. Surgery for patients with thyroid lymphoma peaked in the late 1970s (0.79% of all thyroid operations performed) followed by a significant decline in the 1980s with a current frequency of only 0.16% (p=0.009). A larger number of thyroid resections intended as a curative procedure was performed during the first half of this series compared to the latter half (p=0.05). There was no difference in disease-free survival between patients treated by thyroid resection when compared with an open biopsy (p=0.4875). CONCLUSION: The surgical management of thyroid lymphoma has changed with time. Currently a larger proportion of patients are undergoing surgery in order to achieve a histological diagnosis rather than with therapeutic intent, however, an important role for surgery still exists in the management of a patient with severe airways obstruction.