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World Journal of Surgery Nov 2022Multiple endocrine neoplasia type 1 (MEN1)-associated primary hyperparathyroidism (pHPT) is classically associated with an asymmetric and asynchronous parathyroid... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Multiple endocrine neoplasia type 1 (MEN1)-associated primary hyperparathyroidism (pHPT) is classically associated with an asymmetric and asynchronous parathyroid involvement. Subtotal parathyroidectomy (STP), which is currently the recommended surgical treatment, carries a high risk of permanent hypoparathyroidism. The results of less than subtotal parathyroidectomy (LSTP) are conflicting, and its place in this setting is still a matter of debate. The aim of this study was to identify the place of LSTP in the surgical management of patients with MEN-associated pHPT.
METHODS
A systematic literature review was conducted in accordance with PRISMA and MOOSE guidelines, for studies comparing STP and LSTP for MEN1-associated pHPT. The results of the two techniques, regarding permanent hypoparathyroidism, persistent hyperparathyroidism and recurrent hyperparathyroidism were computed using pairwise random-effect meta-analysis.
RESULTS
Twenty-five studies comparing STP and LSTP qualified for inclusion in the quantitative synthesis. In total, 947 patients with MEN1-associated pHPT were allocated to STP (n = 569) or LSTP (n = 378). LSTP reduces the risk of permanent hypoparathyroidism [odds ratio (OR) 0.29, confidence interval (CI) 95% 0.17-0.49)], but exposes to higher rates of persistent hyperparathyroidism [OR 4.60, 95% CI 2.66-7.97]. Rates of recurrent hyperparathyroidism were not significantly different between the two groups [OR 1.26, CI 95% 0.83-1.91].
CONCLUSIONS
LSTP should not be abandoned and should be considered as a suitable surgical option for selected patients with MEN1-associated pHPT. The increased risk of persistent hyperparathyroidism could improve with the emergence of more efficient preoperative localization imaging techniques and a more adequate patients selection.
Topics: Humans; Hyperparathyroidism, Primary; Hypoparathyroidism; Multiple Endocrine Neoplasia Type 1; Parathyroid Glands; Parathyroidectomy
PubMed: 35767091
DOI: 10.1007/s00268-022-06633-7 -
Endocrine Nov 2023Multiple endocrine neoplasia type 1 (MEN1) is a rare syndrome that combines endocrine and non-endocrine tumors. Thymic neuroendocrine tumors are uncommon components that...
BACKGROUND
Multiple endocrine neoplasia type 1 (MEN1) is a rare syndrome that combines endocrine and non-endocrine tumors. Thymic neuroendocrine tumors are uncommon components that predict poor prognosis in patients with MEN1. We aimed to summarize the clinical characteristics of thymoma in MEN1 by reviewing the current reports from the literature.
METHODS
A patient with multiple endocrine neoplasia type 1 (parathyroid hyperplasia, pituitary adenoma, and insulinoma) was found to have a 2 × 1.5 cm thymic mass during long-term follow-up. Thoracoscope surgery was performed, and a histopathology examination revealed WHO Type B3 thymoma. A pathogenic mutation of c.783 + 1G > A in the MEN1 gene was identified. We further searched PubMed and EMBASE for thymoma in association with MEN1.
RESULTS
A comprehensive overview of the literature concerning characteristics of MEN1-related thymoma was summarized. Clinical characteristics and differences between thymoma and thymic carcinoid are highlighted.
CONCLUSIONS
Besides carcinoid, other tumors, including thymoma, need to be identified for thymic space-occupying lesions in MEN1 patients. The impact of thymoma on the long-term prognosis of MEN1 patients needs further investigation.
Topics: Humans; Multiple Endocrine Neoplasia Type 1; Thymoma; Thymus Neoplasms; Carcinoid Tumor; Pancreatic Neoplasms
PubMed: 37668926
DOI: 10.1007/s12020-023-03440-5 -
Pediatric Surgery International Aug 2014The co-occurrence of Hirschsprung's disease (HSCR) and multiple endocrine neoplasia type 2 (MEN2) is a relatively rare event. The basis for this association is the... (Review)
Review
PURPOSE
The co-occurrence of Hirschsprung's disease (HSCR) and multiple endocrine neoplasia type 2 (MEN2) is a relatively rare event. The basis for this association is the presence of a "Janus" mutation in the RET proto-oncogene--a mutation that acts simultaneously as both a gain-in-function and a loss-of-function mutation. To date, four mutations in the exon 10 region of RET that are known to cause MEN2A have been implicated in this association: C620, C618, C611 and C609. We performed a systematic review of the published literature on this association to determine its incidence, the prevalence and phenotype of HSCR associated with the 4 RET mutations mentioned above.
METHODS
A systematic literature-based search for relevant articles was conducted using three online databases. After exclusion of ineligible publications, we recorded data on all patients with a diagnosis of HSCR or MEN2A with a "Janus" RET mutation, as well as those who carried the mutation but were unaffected. Statistical analysis was performed using SPSS.
RESULTS
The literature search yielded 885 publications, of which 36 articles, incorporating data on 341 individuals, were eligible for inclusion in the final analysis. Co-occurrence of HSCR and MEN2A was recorded in 84 cases (24.6 %). HSCR occurred alone in 64 carriers of a "Janus" mutation (18.8 %) and MEN2A occurred in isolation in 173 cases (50.7 %). Twenty individuals (5.9 %) were found to carry a "Janus" mutation after screening on the basis of family history but were unaffected by either MEN2A or HSCR. The most common mutation recorded was the C620 mutation [114 cases (48.1 %)]. There was a relatively high incidence of long-segment aganglionosis (29.3 %) and total colonic aganglionosis (17.3 %) in this cohort. This trend was particularly notable in those with C620 mutations, only 33 % of whom had short-segment disease.
CONCLUSION
While the overall incidence of HSCR co-occurring with MEN2A is low, both conditions occur with a relatively high frequency in families with a RET mutation at exon 10. The proportion of cases of long-segment HSCR and total colonic aganglionosis is higher than that in the general population with HSCR in those with C620 and C618 mutations. These findings reinforce the importance of RET mutation testing in HSCR when a family history of either HSCR or MEN2 is present. In families with MEN2A and known exon 10 RET mutations, the threshold for investigation for HSCR in those with gastrointestinal symptoms should be very low. High-quality prospective longitudinal studies of large HSCR populations are required to shed greater light on this rare but important phenomenon.
Topics: Child; DNA Mutational Analysis; DNA, Neoplasm; Hirschsprung Disease; Humans; Multiple Endocrine Neoplasia Type 2a; Mutation; Pedigree; Phenotype; Proto-Oncogene Mas; Proto-Oncogene Proteins c-ret
PubMed: 24972642
DOI: 10.1007/s00383-014-3538-2 -
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 -
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 -
World Journal of Surgery Nov 2022
Meta-Analysis
Topics: Humans; Hyperparathyroidism, Primary; Multiple Endocrine Neoplasia Type 1; Multiple Endocrine Neoplasia Type 2a; Neoplasm Recurrence, Local; Parathyroid Glands; Parathyroidectomy
PubMed: 36042033
DOI: 10.1007/s00268-022-06707-6 -
Endocrine Practice : Official Journal... 2011To determine the best surgical strategy for patients with multiple endocrine neoplasia type 2A (MEN 2A) who have primary hyperparathyroidism (PHPT). (Review)
Review
OBJECTIVE
To determine the best surgical strategy for patients with multiple endocrine neoplasia type 2A (MEN 2A) who have primary hyperparathyroidism (PHPT).
METHODS
We performed a systematic literature review and conducted a retrospective cohort study that included patients with PHPT identified from the MEN 2A database at the University Medical Center of Utrecht, Utrecht, the Netherlands, between 1979 and 2009.
RESULTS
The review describes the course of worldwide parathyroid surgical management in MEN 2A PHPT over the past 75 years, which has evolved from aggressive parathyroid resections to minimally invasive parathyroidectomy (MIP). The study cohort included 20 patients. Primary surgery for parathyroid disease in patients with MEN 2A (n = 16) included MIP (n = 6), conventional neck exploration with resection of enlarged parathyroid gland(s) (n = 4), and resection of 1 or more enlarged gland(s) during total thyroidectomy (n = 6). Thirteen patients were initially cured after the primary operation. Five patients experienced persistent or recurrent PHPT. After MIP, 1 patient had persistent PHPT, but no patient developed recurrent PHPT during 5 years of follow-up. Five patients had hypoparathyroidism after subtotal or total parathyroidectomy with autotransplantation, but only 1 patient had transient hypoparathyroidism after MIP. One patient had transient recurrent laryngeal nerve injury after MIP.
CONCLUSIONS
Surgery for PHPT in patients with MEN 2A has evolved from aggressive conventional exploration of all 4 glands to focused MIP, which appears to be a feasible approach. MIP has low rates of persistent and recurrent PHPT, and the complications are minimal.
Topics: Adult; Cohort Studies; Female; Humans; Hyperparathyroidism, Primary; Male; Middle Aged; Minimally Invasive Surgical Procedures; Multiple Endocrine Neoplasia Type 2a; Parathyroidectomy; Treatment Outcome; Young Adult
PubMed: 20570815
DOI: 10.4158/EP10050.OR -
Surgery Feb 2021Hyperparathyroidism is an almost universal feature of multiple endocrine neoplasia type 1 syndrome. We present a systematic review and meta-analysis of the postoperative... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hyperparathyroidism is an almost universal feature of multiple endocrine neoplasia type 1 syndrome. We present a systematic review and meta-analysis of the postoperative outcomes of patients undergoing initial operative treatment of primary hyperparathyroidism complicating multiple endocrine neoplasia 1.
METHODS
A comprehensive literature search was performed with a priori defined exclusion criteria for studies comparing total parathyroidectomy, subtotal parathyroidectomy, and less than subtotal parathyroidectomy.
RESULTS
Twenty-one studies incorporating 1,131 patients (272 undergoing total parathyroidectomy, 510 subtotal parathyroidectomy, and 349 less than subtotal parathyroidectomy) were identified. Pooled results revealed increased risk for long-term hypoparathyroidism in total parathyroidectomy patients (relative risk 1.61; 95% confidence interval, 1.12-2.31; P = .009) versus those undergoing subtotal parathyroidectomy. In the less than subtotal parathyroidectomy or subtotal parathyroidectomy comparison group, a greater risk for recurrence of hyperparathyroidism (relative risk 1.37; 95% confidence interval, 1.05-1.79; P = .02), persistence of hyperparathyroidism (relative risk 2.26; 95% confidence interval, 1.49-3.41; P = .0001), and reoperation for hyperparathyroidism (relative risk 2.48; 95% confidence interval, 1.65-3.73; P < .0001) was noted for less than subtotal parathyroidectomy patients, albeit with lesser risk for long-term for hypoparathyroidism (relative risk 0.47; 95% confidence interval, 0.29-0.75; P = .002).
CONCLUSION
Subtotal parathyroidectomy compares favorably to total parathyroidectomy, exhibiting similar recurrence and persistence rates with a decreased propensity for long-term postoperative hypoparathyroidism. The benefit of the decreased risk of hypoparathyroidism in less than subtotal parathyroidectomy is negated by the increase in the risk for recurrence, persistence, and reoperation. Future studies evaluating the performance of less than subtotal parathyroidectomy in specific multiple endocrine neoplasia 1 phenotypes should be pursued in an effort to delineate a patient-tailored, operative approach that optimizes long-term outcomes.
Topics: Humans; Hyperparathyroidism, Primary; Hypoparathyroidism; Multiple Endocrine Neoplasia Type 1; Parathyroid Glands; Parathyroidectomy; Postoperative Complications; Recurrence; Reoperation; Treatment Outcome
PubMed: 33008613
DOI: 10.1016/j.surg.2020.08.021 -
Journal of Pediatric Surgery Apr 2016A small percentage of pediatric solid cancers arise as a result of clearly identified inherited predisposition syndromes and nongenetic lesions. Evidence supports... (Review)
Review
OBJECTIVE
A small percentage of pediatric solid cancers arise as a result of clearly identified inherited predisposition syndromes and nongenetic lesions. Evidence supports preemptive surgery for children with genetic [multiple endocrine neoplasia type 2 (MEN2), familial adenomatous polyposis syndrome (FAP), hereditary nonpolyposis colorectal cancer (HNPCC), and hereditary diffuse gastric cancer (HDGC) and nongenetic [thyroglossal duct cysts (TGDC), congenital pulmonary airway malformations (CPAM), alimentary tract duplication cysts (ATDC), and congenital choledochal cysts (CCC)] developmental anomalies. Our aim was to explore the utility of risk reduction surgery to treat and prevent cancer in children.
METHODS
A systematic review of the available peer-reviewed literature on PubMed was performed using a PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) search strategy, where possible. Search items included "risk reduction surgery", "hereditary cancer predisposition syndrome", "multiple endocrine neoplasia type 2", "familial adenomatous polyposis", "hereditary nonpolyposis colorectal cancer", "hereditary diffuse gastric cancer", "thyroglossal duct cysts", congenital pulmonary airway malformations", "alimentary tract duplication cysts", "malignant transformation", and "guidelines".
RESULTS
We identified 67 articles that met the inclusion criteria describing the indications for prophylactic surgery in surgical oncology. For the genetic predisposition syndromes, 7 studies were related to professional endorsed guidelines, 7 were related to surgery for MEN2, 11 were related to colectomy for FAP, 6 were related to colectomy for HNPCC, and 12 related to gastrectomy for HDGC. Articles for the nongenetic lesions included 5 for techniques related to TGDC resection, 9 for surgery for CPAMs, and 10 for resection of ATDCs. Guidelines and strategies varied significantly especially related to the extent and timing of surgical intervention; the exception was for the timing of thyroidectomy in children with MEN2.
CONCLUSION
Current evidence supporting prophylactic surgery in the management of pediatric cancer predisposition syndromes and nongenetic lesions is best delineated for thyroidectomy to prevent medullary thyroid cancer in children with MEN2 (Strength of Recommendation Grade B/C). Despite the lack of pediatric specific evidence-based recommendations regarding the appropriate extent and timing for risk-reduction surgery for FAP, HNPCC, HDGC and nongenetic anomalies, our review represents an opportunity towards understanding the postgenomic development of these lesions and provides current indications and techniques for preemptive cancer prevention surgery in children.
Topics: Child; Humans; Neoplastic Syndromes, Hereditary; Pediatrics; Prophylactic Surgical Procedures; Surgical Oncology; Treatment Outcome
PubMed: 26898681
DOI: 10.1016/j.jpedsurg.2016.01.004 -
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