DescriptorName: Multiple EndocrineNeoplasia Type 1... AbstractText: Pancreatic neuroendocrine tumors (pNETs) are highly prevalent in patients with multiple endocrineneoplasia type 1 (MEN1), and metastatic disease is an important cause of MEN1-related mortality. Especially small nonfunctional (NF) pNETs pose a challenge to the treating physician and more information is needed regarding their natural course.
Neoplasms (7), Neuroendocrine Tumors (3), Multiple Endocrine Neoplasia Type 1 (2), more mentions
OBJECTIVE: Flushing can be defined as a sensation of warmth accompanied by erythema that most commonly is seen on the face and which occurs in episodic attacks. Such a problem can be clinically problematic, since many conditions and drugs can be related to flushing, and while often there appears to be no underlying organic disease, it is important to exclude disorders since they may be life-threatening conditions.
DESIGN AND METHODS: We performed a search in MEDLINE using the terms 'flushing' in combination with 'carcinoid syndrome', 'pheochromocytoma', 'mastocytosis', 'menopausal hot flush' and 'treatment'. European and American guidelines relating to neuroendocrine tumours, mastocytosis and menopause were reviewed.
RESULTS: In this review, we discuss the main causes of flushing and propose an algorithm based on pathogenesis, which can be used to guide the clinical evaluation process. We also review recent significant developments in the assessment and treatment of the carcinoid syndrome and menopausal hot flushes, which should guide the clinical practice regarding this common but sometimes confusing condition.
CONCLUSIONS: When evaluating flushing, a precise systematic approach is needed to exclude potentially serious underlying causes, although despite this, the cause of the disorder is not always found. If symptoms are not progressive, the patient should be advised about its apparently benign nature in order to avoid unnecessary studies or initiating treatments of minimal benefit.
Women's Health (2), Endocrine Disorders (1) Pheochromocytoma (2), Mastocytosis (2), Endocrine System Diseases (2), more mentions
Objective To determine if circulating concentrations of vitamin D are causally associated with risk of cancer.Design Mendelian randomisation study.Setting Large genetic epidemiology networks (the Genetic Associations and Mechanisms in Oncology (GAME-ON), the Genetic and Epidemiology of Colorectal Cancer Consortium (GECCO), and the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortiums, and the MR-Base platform).Participants 70 563 cases of cancer (22 898 prostate cancer, 15 748 breast cancer, 12 537 lung cancer, 11 488 colorectal cancer, 4369 ovarian cancer, 1896 pancreatic cancer, and 1627 neuroblastoma) and 84 418 controls.Exposures Four single nucleotide polymorphisms (rs2282679, rs10741657, rs12785878 and rs6013897) associated with vitamin D were used to define a multi-polymorphism score for circulating 25-hydroxyvitamin D (25(OH)D) concentrations.Main outcomes measures The primary outcomes were the risk of incident colorectal, breast, prostate, ovarian, lung, and pancreatic cancer and neuroblastoma, which was evaluated with an inverse variance weighted average of the associations with specific polymorphisms and a likelihood based approach. Secondary outcomes based on cancer subtypes by sex, anatomic location, stage, and histology were also examined.Results There was little evidence that the multi-polymorphism score of 25(OH)D was associated with risk of any of the seven cancers or their subtypes. Specifically, the odds ratios per 25 nmol/L increase in genetically determined 25(OH)D concentrations were 0.92 (95% confidence interval 0.76 to 1.10) for colorectal cancer, 1.05 (0.89 to 1.24) for breast cancer, 0.89 (0.77 to 1.02) for prostate cancer, and 1.03 (0.87 to 1.23) for lung cancer. The results were consistent with the two different analytical approaches, and the study was powered to detect relative effect sizes of moderate magnitude (for example, 1.20-1.50 per 25 nmol/L decrease in 25(OH)D for most primary cancer outcomes. The Mendelian randomisation assumptions did not seem to be violated.Conclusions There is little evidence for a linear causal association between circulating vitamin D concentration and risk of various types of cancer, though the existence of causal clinically relevant effects of low magnitude cannot be ruled out. These results, in combination with previous literature, provide evidence that population-wide screening for vitamin D deficiency and subsequent widespread vitamin D supplementation should not currently be recommended as a strategy for primary cancer prevention.
AbstractText: Radiological tumor size of non-functioning pancreatic neuroendocrine neoplasms (Nf-pNENs) associated with multiple endocrineneoplasia type 1 (MEN1) is a crucial parameter to indicate surgery. The aim of this study was to compare radiological size (RS) and pathologic size (PS) of MEN1 associated with pNENs AbstractText: Prospectively collected data of MEN1 patients who underwent pancreatic resections for pNENs ...
Neoplasms (6), Multiple Endocrine Neoplasia Type 1 (2), more mentions
Context: Adrenal incidentalomas (AIs) are found commonly on axial imaging. Around 30% exhibit autonomous cortisol secretion (ACS) associated with increased cardiovascular events and death.
Objective: We hypothesized that AI/ACS patients have an abnormal cortisol rhythm that could be reversed by use of carefully timed short-acting cortisol synthesis blockade, with improvement in cardiovascular disease markers.
Design, Setting, and Participants: In a phase 1/2a, prospective study (Eudract no. 2012-002586-35), we recruited six patients with AI/ACS and two control groups of six sex-, age-, and body mass index-matched individuals: (1) patients with AI and no ACS (AI/NoACS) and (2) healthy volunteers with no AI [healthy controls (HC)]. Twenty-four-hour circadian cortisol analysis was performed to determine any differences between groups and timing of intervention for cortisol lowering using the 11β-hydroxylase inhibitor metyrapone. Circadian profiles of serum interleukin-6 (IL-6) were assessed.
Results: Serum cortisol levels in group AI/ACS were significantly higher than both group AI/NoACS and group HC from 6 pm to 10 pm [area under the curve (AUC) difference: 0.81 nmol/L/h; P = 0.01] and from 10 pm to 2 am (AUC difference: 0.86 nmol/L/h; P < 0.001). In light of these findings, patients with ACS received metyrapone 500 mg at 6 pm and 250 mg at 10 pm, and cortisol rhythms were reassessed. Postintervention evening serum cortisol was lowered, similar to controls [6 pm to 10 pm (AUC difference: -0.06 nmol/L/h; P = 0.85); 10 pm to 2 am (AUC difference: 0.10 nmol/L/h; P = 0.76)]. Salivary cortisone showed analogous changes. IL-6 levels were elevated before treatment [10 pm to 2 pm (AUC difference: 0.42 pg/mL/h; P = 0.01)] and normalized post treatment.
Conclusions: In AI/ACS, the evening and nocturnal cortisol exposure is increased. Use of timed evening doses of metyrapone resets the cortisol rhythm to normal. This unique treatment paradigm is associated with a reduction in the cardiovascular risk marker IL-6.
Anti-Obesity and Weight Loss (2), Cardiovascular Diseases (1) Cardiovascular Diseases (1), Adrenal Gland Neoplasms (1), more mentions
OBJECTIVE: Recently, the European Society of Endocrinology (ESE), in collaboration with the European Network for the Study of Adrenal Tumors (ENSAT), asserted that adrenal incidentalomas (AIs) <4 cm and ≤10 Hounsfield units (HU) do not require further follow-up imaging. To validate the clinical application of the follow-up strategies suggested by the 2016 ESE-ENSAT guidelines, we explored the clinical characteristics and natural course of AIs in a single center over 13 years.
DESIGN AND METHODS: This retrospective cohort study included a total of 1149 patients diagnosed with AIs between 2000 and 2013 in a single tertiary center. Hormonal examination and radiological evaluations were performed at the initial diagnosis of AI and during the follow-up according to the appropriate guidelines.
RESULTS: The mean age at diagnosis was 54.2 years, and the majority of AIs (68.0%) were nonfunctional lesions. Receiver operating curve analysis was used to discriminate malignant from benign lesions; the optimal cut-off value for mass size was 3.4 cm (sensitivity: 100%; specificity: 95.0%), and that for the pre-contrast HU was 19.9 (sensitivity: 100%; specificity: 67.4%). The majority of nonfunctional lesions did not change in size during the 4-year follow-up period. Applying a cut-off value of 1.8 μg/dL after a 1-mg overnight dexamethasone suppression test, 28.0% of all nonfunctional AIs progressed to autonomous cortisol secretion during the follow-up period. However, we observed no development of overt Cushing's syndrome in the study.
CONCLUSIONS: We advocate that no follow-up imaging is required if the detected adrenal mass is <4 cm and has clear benign features. However, prospective studies with longer follow-up are needed to confirm the appropriate follow-up strategies.
Neoplasms (2), Cushing Syndrome (2), Pheochromocytoma (1), more mentions
RATIONALE: Parathyroid carcinoma is a rare endocrine malignancy. Acute pancreatitis as an initial manifestation of parathyroid carcinoma has been rarely reported.
PATIENT CONCERNS: A 22-year-old woman was admitted to emergency room with a sudden attack of severe epigastric pain.
DIAGNOSES: Acute pancreatitis was diagnosed as elevated levels of serum amylase. During the work-up for acute pancreatitis, patient's abnormally increased serum calcium and bones destruction revealed by abdominal computed tomography (CT) scan raised the suspicion of hyperparathyroidism or malignancy. Elevated serum parathyroid hormone (PTH) levels, parathyroid ultrasound and scintigraphy gave rise to the diagnosis of primary hyperparathyroidism (PHPT) due to a left parathyroid tumor.
INTERVENTIONS: The patient was given a complete tumor excision. After the surgery, parathyroid carcinoma with capsular and vascular invasion was confirmed histologically. A second surgery was then performed, including resection of the ipsilateral thyroid lobe and anterior cervical nodes.
OUTCOMES: Serum calcium and PTH levels returned to normal postoperatively.
LESSONS: Acute pancreatitis accompanied with hypercalcemia should always raise the suspicion of PHPT. The spicule sign, which always suggests the infiltrating pattern growth of tumor, was neglected at first and was observed during a second review of the ultrasound images postoperatively. This specific feature may be predictive for the preoperative diagnosis of parathyroid carcinoma or at least suspicion of malignancy.
Pancreatitis (6), Parathyroid Carcinoma (5), Hyperparathyroidism (3), more mentions
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
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This article has been identified as especially clinically relevant or newsworthy by at least 3
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Purpose Platinum-based chemotherapy (PBC) for patients with progressing ovarian cancer (OC) is more effective with a longer time interval from previous platinum treatment (platinum-free interval [PFI]). In 1999, it was hypothesized that prolonging PFI with single-agent non-PBC (NPBC) may offer a strategy to improve overall outcome. MITO-8 aimed to verify this hypothesis commonly used in clinical practice although it has not been prospectively tested. Methods MITO-8 is an open-label, prospective, randomized, superiority trial. Patients with OC who experienced disease progression 6 to 12 months after their last platinum treatment were randomly assigned 1:1 to the experimental sequence of NPBC followed by PBC at subsequent relapse or the standard reverse treatment sequence. Overall survival (OS) was the primary end point. Results Two hundred fifteen patients were enrolled (standard arm [n = 108]; experimental arm [n = 107]). The trial ended before planned because of slow enrollment. PFI was prolonged in the experimental arm (median, 7.8 v 0.01 months). There was no OS benefit in the experimental arm (median, 21.8 v 24.5 months; hazard ratio, 1.38; 95% CI, 0.99 to 1.94; P = .06). Progression-free survival after the sequence was significantly shorter in the experimental arm (median, 12.8 v 16.4 months; hazard ratio, 1.41; 95% CI, 1.04 to 1.92; P = .025). Global quality-of-life change after three cycles was worse in the experimental arm. Slight differences were observed in the incidence of adverse effects. Conclusion MITO-8 supports the recommendation that PBC not be delayed in favor of an NPBC in patients with partially platinum-sensitive OC. PBC should be used as a control arm in future trials of new drugs in this setting.
BACKGROUND: Real-time elastography (RTE) and shear wave elastography (SWE) are noninvasive and easily available imaging techniques that measure the tissue strain, and it has been reported that the sensitivity and the specificity of elastography were better in differentiating between benign and malignant thyroid nodules than conventional technologies.
METHODS: Relevant articles were searched in multiple databases; the comparison of elasticity index (EI) was conducted with the Review Manager 5.0. Forest plots of the sensitivity and specificity and SROC curve of RTE and SWE were performed with STATA 10.0 software. In addition, sensitivity analysis and bias analysis of the studies were conducted to examine the quality of articles; and to estimate possible publication bias, funnel plot was used and the Egger test was conducted.
RESULTS: Finally 22 articles which eventually satisfied the inclusion criteria were included in this study. After eliminating the inefficient, benign and malignant nodules were 2106 and 613, respectively. The meta-analysis suggested that the difference of EI between benign and malignant nodules was statistically significant (SMD = 2.11, 95% CI [1.67, 2.55], P < .00001). The overall sensitivities of RTE and SWE were roughly comparable, whereas the difference of specificities between these 2 methods was statistically significant. In addition, statistically significant difference of AUC between RTE and SWE was observed between RTE and SWE (P < .01).
CONCLUSION: The specificity of RTE was statistically higher than that of SWE; which suggests that compared with SWE, RTE may be more accurate on differentiating benign and malignant thyroid nodules.
RATIONALE: The spine is the most common site of bone metastases due to thyroid cancer; however, spinal cord compression as a complication of metastatic thyroid cancer is very rare.
PATIENT CONCERNS: A 48-year-old female patient was presented to the Neurosurgical Department, complaining of progressive back neck pain with bilateral upper extremities numbness and weakness for 4 months.
DIAGNOSIS: Imaging studies revealed osteolytic destruction in bodies and accessories of the second and third cervical vertebrae with a huge soft-tissue mass compressing spinal cord and causing swelling. After the neurosurgical decompression surgery, the pathological examination established a metastatic follicular carcinoma originating from the thyroid gland.
INTERVENTIONS: Her cervical spinal metastases were hardly removed by surgery and the risks of external beam radiation therapy (EBRT) were very high. So she underwent a total thyroidectomy and received multiple radioiodine (RAI) and concomitant glucocorticoid therapies postoperatively. Radioiodine whole-body scan (WBS) showed multiple abnormal radioiodine uptakes. Then single-photon emission tomography/computed tomography (SPECT/CT) located these spinal metastases involving cervical, lumbar, and sacral vertebrae.
OUTCOMES: After 5 times RAI therapy, her thyroglobulin obviously decreased, with the cervical lesion shrinkage and no spinal cord edema.
LESSONS: RAI therapy and concomitant glucocorticoid therapy could be used for spinal metastases of FTC, even with spinal cord compression.
OBJECTIVE: Changes in the clinicopathological characteristics and genetic alterations of follicular thyroid cancer (FTC) over time have not been reported. Moreover, the prognostic effects of RAS and TERT promoter mutations in FTC have not been clearly elucidated. We investigated changes in the clinicopathological characteristics of patients with FTC over four decades, as well as the clinical significance of genetic mutations of FTC.
DESIGN AND METHODS: This retrospective study included 690 patients with FTC who underwent thyroidectomy between 1973 and 2015 at the Seoul National University Hospital. In 134 samples, genetic tests for N/H/KRAS and TERT promoter mutations and PAX8/PPARγ rearrangement were performed.
RESULTS: The age at diagnosis has increased (P < 0.001) in recent decades and extrathyroidal extension of the tumor has become less common (P = 0.033). Other clinicopathological characteristics and prognosis of FTC have not significantly changed. The prevalence of RAS mutations decreased (P = 0.042) over time, whereas that of TERT promoter mutations remained stable. RAS mutations were associated with distant metastasis and persistent disease, and TERT promoter mutations were associated with distant metastasis, advanced TNM stage, recurrence and disease-specific mortality. FTC patients with coexistent RAS and TERT promoter mutations showed a higher recurrence risk than those with only one mutation.
CONCLUSIONS: The age at diagnosis of FTC and the frequency of extrathyroidal extension have changed over four decades. Moreover, the prevalence of RAS mutations decreased. RAS and TERT promoter mutations may be associated with poor clinical outcomes in FTC, especially when the two mutations coexist.
CONTEXT: Inflammatory infiltrates are sometimes present in solid tumors and may be coupled to clinical behavior or etiology. Infectious viruses contribute to tumorigenesis in a significant fraction of human neoplasias.
OBJECTIVE: Characterize inflammatory infiltrates and possible viral transcription in primary hyperparathyroidism.
DESIGN: From the period 2007 to 2016, a total of 55 parathyroid tumors (51 adenomas and 4 hyperplasias) with prominent inflammatory infiltrates were identified from more than 2000 parathyroid tumors in the pathology archives, and investigated by immunohistochemistry for CD4, CD8, CD20 and CD45 and scored as +0, +1 or +2. Clinicopathological data were compared to 142 parathyroid adenomas without histological evidence of inflammation. Transcriptome sequencing was performed for 13 parathyroid tumors (four inflammatory, 9 non-inflammatory) to identify potential viral transcripts.
RESULTS: Tumors had prominent germinal center-like nodular (+2) lymphocytic infiltrates consisting of T and B lymphocytes (31%) and/or diffuse (+1-2) infiltrates of predominantly CD8+ T lymphocytes (84%). In the majority of cases with adjacent normal parathyroid tissue, the normal rim was unaffected by the inflammatory infiltrates (96%). Presence of inflammatory infiltrates was associated with higher levels of serum-PTH (P = 0.007) and oxyphilic differentiation (P = 0.002). Co-existent autoimmune disease was observed in 27% of patients with inflammatory infiltrates, which in turn was associated with oxyphilic differentiation (P = 0.041). Additionally, prescription of anti-inflammatory drugs was associated with lower serum ionized calcium (P = 0.037).
CONCLUSIONS: No evidence of virus-like sequences in the parathyroid tumors could be found by transcriptome sequencing, suggesting that other factors may contribute to attract the immune system to the parathyroid tumor tissue.
Immune System Diseases (1) Neoplasms (8), Hyperparathyroidism (2), Adenoma (2), more mentions
We assessed the clinical significance and risk factors of incidental parathyroidectomy during total thyroidectomy with or without central neck dissection or subtotal thyroidectomy.Retrospective analysis of clinical and pathological features of 548 consecutive thyroidectomy cases was compared by grouping into inadvertent resection (IR, n = 86) with IR of parathyroid glands, non-IR (n = 462) without, and then into postoperative hypoparathyroidism (PH, n = 140) with PH and non-PH (n = 408) without.Two hundred ninety-eight patients had total thyroidectomy and 250 had subtotal thyroidectomy. IR had higher malignant disease (P < .001), total thyroidectomy (P = .016), T3 and T4 classification (P = .005), central neck dissection (P < .001), recurrent laryngeal nerve palsy (P = .003), postoperative transient hypoparathyroidism (P < .001), duration of disease prior to thyroidectomy (P < .001), and weight of excised thyroid tissue (P < .001) than non-IR.Preoperative diagnosis of malignant disease, duration of disease prior to thyroidectomy, and central neck dissection were independent risk factors for incidental parathyroidectomy. Preoperative diagnosis of malignant disease, central neck dissection, duration of disease prior to thyroidectomy, weight of excised thyroid tissue, and incidental parathyroidectomy were correlated with PH.
... was to investigate the genotype-phenotype relationship of pancreatic neuroendocrine tumors in patients with multiple endocrineneoplasia type 1 treated at our institution AbstractText: We conducted a retrospective chart review of all patients with multiple endocrineneoplasia type 1 treated at our center from January 1993 to ... The most common site of multiple endocrineneoplasia type 1 mutation was in exon 2 (34/188; 18 ...
Oncology (2) Neuroendocrine Tumors (8), Multiple Endocrine Neoplasia Type 1 (5), more mentions
Our treatment approach for either symptomatic or incidentally found pancreatic cysts continues to improve. The true incidence of pancreatic cysts is not known, and pancreatic cystic neoplasms, especially intraductal papillary mucinous neoplasms, are currently most commonly diagnosed and resected. This is a result of increasing awareness, widespread availability of imaging, and better understanding of the nature of pancreatic cysts as well. Recent studies on molecular analysis and devices such as microbiopsy forceps help us better define and select the treatment approach to alleviate symptoms and to prevent malignant tumors while avoiding unnecessary surgery.
Pancreatic Cysts (5), Neoplasms (3), Pancreatic Neoplasms (1), more mentions
The risk factors of hypoparathyroidism after total thyroidectomy (TT) with central lymph node dissection (CND) have not been completely defined. The aim of the study was to evaluate the risk factors of hypoparathyroidism after the surgery.We retrospectively reviewed our patients who underwent TT and CND (including lateral lymph node dissection) for thyroid carcinoma between January 2013 and June 2016. According to the postoperative serum levels of parathyroid hormone within 6 months, the patients were divided into normal, transient hypoparathyroidism, and permanent hypoparathyroidism groups. The clinicopathologic characteristics and surgical details were compared among the 3 groups. The risk factors of hypoparathyroidism were investigated by univariate and multivariate analyses.Of the 903 patients, 399 (44.2%) were found to have transient hypoparathyroidism and 10 (1.1%) had permanent hypoparathyroidism. On multivariate analysis, female gender (P < .001), nonuse of carbon nanoparticles (P = .038), parathyroid autotransplantation (P < .001), accidental parathyroid resection (P = .004), and bilateral CND (BCND, P = .003) were the independent risk factors of transient hypoparathyroidism; nonuse of carbon nanoparticles (P = .041) and a tumor in the upper pole of thyroid gland (P = .031) were the independent risk factors of permanent hypoparathyroidism. Patients with transient hypoparathyroidism were more likely to develop permanent hypoparathyroidism when they had hypertension (P = .026) and a tumor in the upper pole of thyroid gland (P = .010).Precise surgical techniques and carbon nanoparticles suspension should be applied for in situ preservation of parathyroid glands (PGs) in thyroid carcinoma patients, especially in females with hypertension and a tumor in the upper pole of thyroid gland. Autotransplantation is only performed when a PG is resected inadvertently or devascularized. TT with BCND should be better performed by an experienced surgeon to reduce the incidence of hypoparathyroidism.