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Endocrine, Metabolic & Immune Disorders... 2021Multiple endocrine neoplasia type 2B (MEN 2B) is mainly caused by M918T RET germline mutation, and characterized by medullary thyroid carcinoma (MTC), pheochromocytoma...
BACKGROUND
Multiple endocrine neoplasia type 2B (MEN 2B) is mainly caused by M918T RET germline mutation, and characterized by medullary thyroid carcinoma (MTC), pheochromocytoma (PHEO) and non-endocrine features. However, the diagnosis and treatment are usually delayed.
METHODS
This study reports 5 Chinese pedigrees with 5 individuals harboring germline RETM918T, and systematically reviewed previous Chinese literature reported.
RESULTS
All 5 patients initially presented MTC, but none had biochemically cured postoperatively. 2 also presented bilateral PHEO after adrenal-sparing surgery, 1 needed steroid replacement. Further, a total of 32 MEN 2B patients from literature were clustered with 28 available for analysis. 26 (92.8%) were diagnosed by endocrine-related symptoms; the remaining 2 (7.2%) due to RET testing and oral symptoms, respectively. 25 patients underwent thyroidectomy with/without neck lymph node dissection at the mean age of (23.3 ± 10.4) years. Histopathological examination revealed MTC (100%). Of them, 17 had definite TNM stage, with 1 in stage III and others in IV. Other information of MEN 2B-related symptoms included penetrance of PHEO (60.7%), constipation (32.1%), Hirschsprung disease (25%), alacrima (17.8%), mucosal ganglioneuroma (96.4%) and marfanoid habitus (71.4%). 19 patients were verified harboring RET-M918T (c.2753T>C), of whom 15 (78.9%) were de novo mutation. The other 9 were clinically diagnosed as MEN 2B.
DISCUSSION & CONCLUSION
The initial diagnosis of MEN 2B is relatively later, and diagnosed by non-endocrine components is extremely lower. Recognition of MEN 2B and its non-endocrine-related components is still the utmost requirement for a Chinese physician. Combined RET screening and serum calcitonin detection can facilitate early diagnosis.
Topics: Adolescent; Adult; Asian People; Biomarkers, Tumor; Calcitonin; Child; China; DNA Mutational Analysis; Early Detection of Cancer; Female; Genetic Predisposition to Disease; Heredity; Humans; Lymph Node Excision; Male; Middle Aged; Multiple Endocrine Neoplasia Type 2b; Mutation; Pedigree; Predictive Value of Tests; Proto-Oncogene Mas; Proto-Oncogene Proteins c-ret; Risk Factors; Thyroidectomy; Treatment Outcome; Young Adult
PubMed: 32914730
DOI: 10.2174/1871530320666200910112230 -
Endocrine-related Cancer Jun 2020Metastatic duodenopancreatic neuro-endocrine tumors (dpNETs) are the most important disease-related cause of death in patients with multiple endocrine neoplasia type 1...
Metastatic duodenopancreatic neuro-endocrine tumors (dpNETs) are the most important disease-related cause of death in patients with multiple endocrine neoplasia type 1 (MEN1). Nonfunctioning pNETs (NF-pNETs) are highly prevalent in MEN1 and clinically heterogeneous. Therefore, management is controversial. Data on prognostic factors for risk stratification are limited. This systematic review aims to establish the current state of evidence regarding prognostic factors in MEN1-related NF-pNETs. We systematically searched four databases for studies assessing prognostic value of any factor on NF-pNET progression, development of distant metastases, and/or overall survival. In- and exclusion, critical appraisal and data-extraction were performed independently by two authors according to pre-defined criteria. Thirteen studies (370 unique patients) were included. Prognostic factors investigated were tumor size, timing of surgical resection, WHO grade, methylation, p27/p18 expression by immunohistochemistry (IHC), ARX/PDX1 IHC and alternative lengthening of telomeres. Results were complemented with evidence from studies in MEN1-related pNET for which data could not be separately extracted for NF-pNET and data from sporadic NF-pNET. We found that the most important prognostic factors used in clinical decision making in MEN1-related NF-pNETs are tumor size and grade. NF-pNETs <2 cm may be managed with watchful waiting, while surgical resection is advised for NF-pNETs ≥2 cm. Grade 2 NF-pNETs should be considered high risk. The most promising and MEN1-relevant avenues of prognostic research are multi-analyte circulating biomarkers, tissue-based molecular factors and imaging-based prognostication. Multi-institutional collaboration between clinical, translation and basic scientists with uniform data and biospecimen collection in prospective cohorts should advance the field.
Topics: Female; Humans; Male; Multiple Endocrine Neoplasia Type 1; Prognosis; Treatment Outcome
PubMed: 32229700
DOI: 10.1530/ERC-19-0372 -
Environmental Research May 2020Environmental exposure to nonylphenol (NP) can adversely affect human and wildlife health. A systematic review was conducted to evaluate the relationship between...
Environmental exposure to nonylphenol (NP) can adversely affect human and wildlife health. A systematic review was conducted to evaluate the relationship between environmental NP exposure and cancer progression risk. Literature surveys were conducted within several international databases using appropriate keywords. A comprehensive search yielded 58 eligible studies involving a wide range of adverse effects, exposure assessment methods, study designs, and experimental models. Most studies reported that NP strongly induced breast cancer progression in intended experiments. Positive associations between NP exposure and ovarian, uterine, pituitary, and testicular cancers were also reported. Although some studies reported no relation between environmental NP exposure and tumour and/or cancer progression, NP (a known endocrine disrupting chemical) induced action mechanisms in multiple experimental models and may interfere with/hyper-activate oestrogen signalling. Secretion of oestrogen and development of reproductive tissues like breasts, uteruses, and ovaries showed strong associations with possible neoplasia (i.e., uncontrolled development of tumours and/or malignant cancers). Findings of this study are important for informing policymakers to pass legislation limiting the use of environmental contaminants such as NP before all adverse effects of exposure have been determined.
Topics: Endocrine Disruptors; Environmental Exposure; Estrogens; Humans; Neoplasms; Phenols; Reproduction
PubMed: 32113025
DOI: 10.1016/j.envres.2020.109263 -
Pancreatology : Official Journal of the... Jul 2019The clinicopathological features and biological behaviors of cystic pancreatic neuroendocrine tumors (pNETs) are unclear and controversial. Here we performed a... (Meta-Analysis)
Meta-Analysis
BACKGROUND/OBJECTIVES
The clinicopathological features and biological behaviors of cystic pancreatic neuroendocrine tumors (pNETs) are unclear and controversial. Here we performed a systematic review and meta-analysis to investigate the unique characteristics of cystic pNETs, to determine whether they represent a distinct clinical entity.
METHODS
We selected comparative studies published since January 2000 that explore the differences between clinicopathological features of cystic and solid pNETs. Demographic information, pathological characteristics, and survival information were analyzed.
RESULT
The 12 selected studies comprised 355 and 1530 patients diagnosed with cystic and solid pNETs, respectively. Compared with solid pNETs, cystic pNETs were less likely to be functional (odds ratio, OR = 0.31, 95% confidence interval (CI) 0.19-0.50, p < 0.00001), more likely to affect males (OR = 1.56, 95% CI 1.22-2.00, p = 0.0005), and significantly associated with multiple endocrine neoplasia type 1 (OR = 2.71). Cystic pNETs were more likely to present with G1 and G2 rather than G3 (OR = 1.66). Cystic pNETs were associated with less frequent distant organs and lymph node metastasis, microvascular invasion, perineural invasion, and a low Ki-67 index and mitotic count. There were no significant differences between 5- and 10-year overall survival. However, the 5-year disease-free survival (DFS) and 10-year DFS rate of patients with cystic pNETs was significantly higher compared with those with solid pNETs (94.6% vs 83.5%, OR = 3.00; 92.7% vs 63.6%, OR = 5.92, respectively).
CONCLUSIONS
Cystic pNETs represent a distinct subgroup of pNETs that present with an indolent biological behavior, and patients experience better DFS. Observation and surveillance should be considered in some selected cases.
Topics: Humans; Neuroendocrine Tumors; Pancreatic Neoplasms; Prognosis
PubMed: 31160191
DOI: 10.1016/j.pan.2019.05.462 -
JAMA Otolaryngology-- Head & Neck... Aug 2019Identifying parathyroid glands correctly before a surgical procedure is essential to perform minimally invasive surgery. First-line tests with discordant or negative...
IMPORTANCE
Identifying parathyroid glands correctly before a surgical procedure is essential to perform minimally invasive surgery. First-line tests with discordant or negative results underscore the need for more accurate imaging tests, thus decreasing the requirement for bilateral neck exploration or reintervention.
OBJECTIVE
To review the available evidence to determine positive predictive value, negative predictive value, sensitivity, and specificity in clinical cases in which 18F-fluorocholine positron emission tomography-computed tomography (PET/CT) could be useful as a method to locate the lesions, and the benefits and controversial aspects of the method.
EVIDENCE REVIEW
A search was conducted using the PubMed Central and Cochrane Library databases for studies published in English from July 26, 2014, to November 30, 2018, using the search terms 18 choline, 18F choline, 18F-choline, 18 fluorocholine PET CT, hyperparathyroidism, primary hyperparathyroidism, secondary hyperparathyroidism, tertiary hyperparathyroidism, persistent hyperparathyroidism, recurrent hyperparathyroidism, ectopic hyperparathyroidism, and parathyroid adenoma. Other inclusion criteria were reporting at least 1 of the following measurements: negative or positive predictive value, sensitivity, and specificity of 18F-fluorocholine PET/CT in the diagnosis of hyperparathyroidism (HPT). Exclusion criteria were language other than English, use of a tracer other than 18F-fluorocholine, reports of a single case, and studies not related to HPT. The Oxford Centre classifications for levels of evidence were used.
FINDINGS
Sixteen studies fulfilled the inclusion criteria, comprising a total of 619 patients. Selected studies included 10 prospective cohort studies, 5 retrospective cohort studies, and 1 case series. Of the subtypes of HPT diagnosed using 18F-fluorocholine PET/CT, 579 were primary HPT, 22 were secondary HPT, 1 was tertiary HPT, and 7 were associated with multiple endocrine neoplasia type I. Pathologically, the neoplasms comprised 459 adenomas, 59 hyperplasia, and 19 double adenomas.
CONCLUSIONS AND RELEVANCE
18F-fluorcholine PET/CT may be indicated when results of first-line tests are negative or discordant and in challenging clinical situations where locating the source of HPT is difficult.
PubMed: 31145436
DOI: 10.1001/jamaoto.2019.0574 -
Pancreatology : Official Journal of the... Apr 2019This systematic review aimed to define the outcomes of different pancreatic resection procedures for multiple endocrine neoplasia type 1 (MEN1) associated pancreatic...
Patient characteristics and clinical outcomes following initial surgical intervention for MEN1 associated pancreatic neuroendocrine tumours: A systematic review and exploratory meta-analysis of the literature.
BACKGROUND
This systematic review aimed to define the outcomes of different pancreatic resection procedures for multiple endocrine neoplasia type 1 (MEN1) associated pancreatic neuroendocrine neoplasms (pNENs).
METHODS
A search of PubMed, MEDLINE and SCOPUS databases were performed in accordance with PRISMA guidelines.
RESULTS
Twenty-seven studies including 533 patients undergoing initial pancreatic resection for MEN1 associated pNENs were included in this systematic review. Three hundred and sixty-six (68.7%) distal pancreatectomies (DP), 120 (22.5%) sole enucleations (SE) and 47 (8.8%) pancreaticoduodenectomies (PD) were identified. SE was associated with a higher rate of recurrence than DP (25/67, 37% vs 40/190, 21% respectively, P = 0.008) but a lower rate of endocrine insufficiency than PD (1/20, 5% vs 8/21, 38% respectively, P = 0.010). A meta-analysis of major pancreatic resections (PD or DP) vs SE in 15 studies showed that SE is associated with an increased rate of recurrence (Major resection 42/184, 23% vs SE 20/53, 38% RR 0.65 CI 0.43-0.96 P = 0.032) but reduced rate of postoperative endocrine insufficiency (Resection 37/93, 40% vs SE 0/24, 0% RR 7.37 CI 1.57-34.64 P = 0.008). Similarly, insulinomas and functional pNENs overall had lower rates of recurrence and reoperation with major resection. There was no difference in the reoperation rates or survival outcomes after SE compared with major pancreatic resections at follow-up (pooled overall mean duration: 85 months).
CONCLUSION
Major pancreatic resections for MEN1 associated pNENs have a lower risk of recurrence and a higher risk of postoperative endocrine insufficiency when compared to sole enucleation, but a similar rate of reoperation and survival.
Topics: Gene Expression Regulation, Neoplastic; Humans; Neuroendocrine Tumors; Pancreatectomy; Pancreatic Neoplasms; Proto-Oncogene Proteins
PubMed: 30894303
DOI: 10.1016/j.pan.2019.03.002 -
Clinical and Experimental Medicine Nov 2018The aim of this report was to illustrate a case of parathyroid carcinoma (PC) in a patient with multiple endocrine neoplasia type 1 (MEN1) along with a comprehensive...
The aim of this report was to illustrate a case of parathyroid carcinoma (PC) in a patient with multiple endocrine neoplasia type 1 (MEN1) along with a comprehensive literature review. A 61-year-old man presented with 9-cm PC causing primary hyperparathyroidism (PHPT). His pre-operative corrected calcium and intact PTH serum levels were 2.92 mmol/L and 391.7 pg/mL, respectively. The neoplastic gland was removed in bloc with thyroid and central compartment lymph nodes. A literature review was run by searching PubMed MEDLINE from 1977 to 2018 for studies of all types, in the English language only, using the terms "Parathyroid, carcinoma, Multiple endocrine neoplasia, type 1, (MEN1)." Pathology confirmed PC. Post-operative calcium and PTH levels were normal. A diagnosis of MEN1 was established post-operatively. Seventeen cases of PC in patients with MEN1 have been reported in the literature. 59% of patients were men, and median age at diagnosis was 50 years, with median serum PTH of 379 pg/mL and median serum calcium level of 3.2 mmol/L. The occurrence of PC in the context of MEN1 is extremely rare. Diagnosis and treatment may represent a challenge, so opportune identification or suspicion of malignancy and adoption of correct surgical approach may offer affected patients the best outcome.
Topics: Calcium; Comorbidity; Humans; Hyperparathyroidism, Primary; Male; Middle Aged; Multiple Endocrine Neoplasia Type 1; Parathyroid Hormone; Parathyroid Neoplasms; Tomography, X-Ray Computed
PubMed: 29922966
DOI: 10.1007/s10238-018-0512-7 -
Revista Espanola de Enfermedades... Nov 2017Cystic pancreatic neuroendocrine tumors represent 13% of all neuroendocrine tumors. The aim of this study is to analyze the phenotype and biologic behavior of resected... (Meta-Analysis)
Meta-Analysis Review
Cystic pancreatic neuroendocrine tumors represent 13% of all neuroendocrine tumors. The aim of this study is to analyze the phenotype and biologic behavior of resected cystic neuroendocrine tumors. A systematic review and meta-analysis were conducted until September 2016 using a search in Medline, Scopus, and EMBASE with the terms "cystic pancreatic endocrine neoplasm", "cystic islets tumors" and "cystic islets neoplasms". From the 795 citations recovered 80 studies reporting on 431 patients were selected. 87.1% (n = 387) were sporadic tumors and 10.3% (n = 40) corresponded to multiple endocrine neoplasia endocrine type 1. Were diagnosed incidentally 44.6% (n = 135). Cytology was found to have a sensitivity of 78.5%. Were non-functional tumors 85% (n = 338), and among the functional tumors, insulinoma was the most frequent. According to the European Neuroendocrine Tumor Society staging, 87.8% were limited to the pancreas (I-IIb), and 12.2% were advanced (III-IV). Disease-free survival at 5 years in stages (I-IIIa) and (IIIb-IV) was 91.5% and 54.2%, respectively; and was significantly lower (p = 0.0001) in functional tumors. In patients with multiple endocrine neoplasia there was a higher incidence of functional (62.5%) and multifocal (28.1%) tumors. Disease-free survival at 5 and 10 years was 60%. Cystic pancreatic neuroendocrine tumors exhibit phenotypical characteristics which are different to those of solid neuroendocrine tumors.
Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Neuroendocrine Tumors; Pancreatectomy; Pancreatic Cyst; Pancreatic Neoplasms; Treatment Outcome
PubMed: 29072081
DOI: 10.17235/reed.2017.5044/2017 -
Clinical Endocrinology Dec 2017Thymic neuroendocrine tumour (TH-NET) accounts for almost 20% of multiple endocrine neoplasia type 1 (MEN1)-associated mortality. Identifying risk factors for the... (Meta-Analysis)
Meta-Analysis Review
Clinical features and prognosis of thymic neuroendocrine tumours associated with multiple endocrine neoplasia type 1: A single-centre study, systematic review and meta-analysis.
OBJECTIVE
Thymic neuroendocrine tumour (TH-NET) accounts for almost 20% of multiple endocrine neoplasia type 1 (MEN1)-associated mortality. Identifying risk factors for the development of these rare tumours and prognostic factors for clinical outcomes will be helpful in clinical practice.
DESIGN AND PATIENTS
We performed a retrospective analysis of patients treated for TH-NET associated with MEN1 in a single institution and meta-analysis of literature reports. We used a fixed effect model to pool results across studies to evaluate the prevalence, clinical features and prognosis.
RESULTS
TH-NET was detected in 9 (7.4%) of 121 patients with MEN1 seen in our institution, and 5 (55.6%) were women. Seven additional studies were identified through a systematic review of the literature. The pool estimate of TH-NET prevalence was 3.7% (n = 99) in MEN1 (n = 2710), sex ratio was 79:20 (male vs female), and the median age at diagnosis was 43.0 years (range, 16.0-72.0 years). Forty-three patients died with a median survival time of 8.4 years. Older age at diagnosis (HR = 1.4, 95% CI = 1.0-1.8, P = .03), maximum tumour diameter (HR = 1.5, 95% CI = 1.0-2.3, P = .04) and presence of metastasis (HR = 1.6, 95% CI = 1.0-2.5, P = .04) were associated with worse outcome. A male predominance (91.9% vs 59.5%, P < .001) and history of smoking (59.0% vs 23.5%, P = .015) were more common in American/European series compared to Asian reports.
CONCLUSION
TH-NET is a rare but fatal component of MEN1. Earlier detection of TH-NET in patients with MEN1 may be recommended which should theoretically result in better outcomes. Different genetic backgrounds (race) appear to result in clinical difference.
Topics: Female; Humans; Male; Multiple Endocrine Neoplasia Type 1; Neuroendocrine Tumors; Prognosis; Thymus Neoplasms
PubMed: 28940393
DOI: 10.1111/cen.13480 -
Journal of Pediatric Surgery Jul 2017Gastrointestinal symptoms are very common in patients with multiple endocrine neoplasia type 2B (MEN2B) syndrome. Herein, we present a case of intestinal... (Review)
Review
BACKGROUND/PURPOSE
Gastrointestinal symptoms are very common in patients with multiple endocrine neoplasia type 2B (MEN2B) syndrome. Herein, we present a case of intestinal ganglioneuromatosis (IGN) in MEN2B syndrome and a systematic literature review with a special focus on gastrointestinal symptoms prior to the diagnosis of MEN2B.
METHODS
Literature search was performed (years 1966-2015) using the "Pubmed" and "Scopus" databases. Search terms used were gastrointestinal, intestinal and MEN2B.
RESULTS
Literature search revealed 188 publications on MEN2B patients with gastrointestinal symptoms, providing a total of 55 patients including our own case. The far most common gastrointestinal symptom was constipation (72.7%). The onset of gastrointestinal symptoms occurred in 29 out of 55 cases (52.3%) below the age of 1year. However, MEN2B diagnosis was established at a median age of 13.0years (range 0-46years). The histological finding of IGN led to the diagnosis of MEN2B In 15 of 55 patients (27.3%) at a median age of 3years (range 0-31years).
CONCLUSION
Paying close attention to gastrointestinal problems in early childhood and taking a rectal biopsy that precisely screens for IGN offers the chance of diagnosing MEN2B syndrome early in infancy.
Topics: Adolescent; Adult; Biopsy; Child; Child, Preschool; Constipation; Early Detection of Cancer; Female; Ganglioneuroma; Humans; Infant; Intestinal Neoplasms; Male; Middle Aged; Multiple Endocrine Neoplasia Type 2b; Young Adult
PubMed: 27899172
DOI: 10.1016/j.jpedsurg.2016.10.054