Thyroid disease in pregnancy is a common clinical problem. Since the guidelines for the management of these disorders by the American Thyroid Association (ATA) were first published in 2011, ...significant clinical and scientific advances have occurred in the field. The aim of these guidelines is to inform clinicians, patients, researchers, and health policy makers on published evidence relating to the diagnosis and management of thyroid disease in women during pregnancy, preconception, and the postpartum period.
The specific clinical questions addressed in these guidelines were based on prior versions of the guidelines, stakeholder input, and input of task force members. Task force panel members were educated on knowledge synthesis methods, including electronic database searching, review and selection of relevant citations, and critical appraisal of selected studies. Published English language articles were eligible for inclusion. The American College of Physicians Guideline Grading System was used for critical appraisal of evidence and grading strength of recommendations. The guideline task force had complete editorial independence from the ATA. Competing interests of guideline task force members were regularly updated, managed, and communicated to the ATA and task force members.
The revised guidelines for the management of thyroid disease in pregnancy include recommendations regarding the interpretation of thyroid function tests in pregnancy, iodine nutrition, thyroid autoantibodies and pregnancy complications, thyroid considerations in infertile women, hypothyroidism in pregnancy, thyrotoxicosis in pregnancy, thyroid nodules and cancer in pregnant women, fetal and neonatal considerations, thyroid disease and lactation, screening for thyroid dysfunction in pregnancy, and directions for future research.
We have developed evidence-based recommendations to inform clinical decision-making in the management of thyroid disease in pregnant and postpartum women. While all care must be individualized, such recommendations provide, in our opinion, optimal care paradigms for patients with these disorders.
A growing body of literature is demonstrating that Notch signaling is a more complex process than originally thought. Contradictory findings of notch‐1 acting as an oncogene or a tumor suppressor ...revealed that its role is very specific to the cellular context. In this review we focus on the tumor suppressor role of Notch‐1 signaling in neuroendocrine tumors (NETs) such as carcinoid and medullary thyroid cancers. NETs secrete various bioactive hormones that can cause debilitating symptoms. Surgery is the only potential curative treatment for the patients with NETs. Notch‐1 signaling is absent in these tumors and activation of Notch‐1 significantly reduces tumor growth in vitro. Therefore, identification of compound(s) that activate the Notch‐1 pathway in NETs could be a potential strategy to treat patients with NETs.
Disclosure of potential conflicts of interest is found at the end of this article.
Learning Objectives
Identify and evaluate a patient with a diagnosis of medullary thyroid cancer.
Utilize genetic testing for the RET proto‐oncogene and explain how the location of the mutation ...affects the risks for the patient.
Select among the surgical treatment options for patients with medullary thyroid cancer, including prophylactic surgery in genetic carriers.
Medullary thyroid cancer (MTC) typically accounts for 3%–4% of all thyroid cancers. Although the majority of MTCs are sporadic, 20% of cases are hereditary. Hereditary MTC can be found in multiple endocrine neoplasia 2A or 2B or as part of familial MTC based on a specific germline mutation in the RET proto‐oncogene. This article discusses the current approaches available for the diagnosis, evaluation, and management of patients and their family members with suspected MTC. The disease is predominantly managed surgically and typically requires a total thyroidectomy and lymph node dissection. A review of recent guidelines on the extent and timing of surgical excision is discussed. There are not very many effective systemic treatment options for MTC, but several emerging therapeutic targets have promise.
摘要
甲状腺髓样癌 (MTC) 在所有甲状腺癌中通常占 3%–4%。虽然大多数 MTC 呈散发性，但有 20% 的病例是遗传性病例。根据 RET 原癌基因上的一个特定胚系突变，遗传性 MTC 可归类于 2A 或 2B 型多发性内分泌肿瘤综合征或者家族性 MTC 的组成部分。本文讨论了 MTC 疑似患者及其家人的最新诊断、评估和治疗方案。该疾病的主要治疗手段是手术治疗，通常需要进行甲状腺全切术和淋巴结清扫术。本文对最新指南中的手术切除范围和时机进行了总结。针对 MTC 的有效全身治疗方案，目前还不是很多，但新近发现的若干治疗靶标为 MTC 患者带来了希望。The Oncologist 2013; 18:1093–1100
This article discusses the current approaches available for the diagnosis, evaluation, and management of patients and their family members with suspected medullary thyroid cancer. A review of recent guidelines on the extent and timing of surgical excision is discussed. There are not very many effective systemic treatment options for MTC, but several emerging therapeutic targets have promise.
Background
Parathyroidectomy has a success rate of >95 % for cure of primary hyperparathyroidism. In about 6–16 % of cases, one or more hyperfunctioning parathyroid gland(s) are found in an ectopic ...location. Accurate preoperative imaging can aid in detecting these ectopically located glands and allow a focused surgical approach with an even higher success rate. The objective of this study was to assess the utility of ultrasonography (US) and technetium-99m-sestamibi (MIBI) scans in locating ectopic parathyroid glands in previously unexplored patients who presented with primary hyperparathyroidism.
Methods
We analyzed a total of 1,562 patients who underwent surgery for hyperparathyroidism at our institution from 2000 to 2010. Ectopic parathyroid adenomas were identified in 346 of the patients (22 %). Of the 346 patients, we excluded 144 who underwent reoperations, had four-gland hyperplasia or were missing imaging details. We carefully reviewed the data, including demographics, laboratory values, preoperative localizing imaging details, and operative findings. Preoperative US and MIBI results were compared to the intraoperative findings.
Results
We analyzed 202 patients with ectopic glands for accuracy of preoperative localization. Of these 202 patients, a single adenoma was the most common (89 %) followed by double adenoma (11 %). The ectopic parathyroid glands were predominantly located in the thymus (38 %) followed by 31 % in the retroesophageal region; 18 % were intrathyroidal. Preoperative MIBI scans had a sensitivity of 89 % (161/197), whereas US had a sensitivity of 59 % (35/63) for detecting ectopic glands. Overall, both imaging modalities had a positive predictive value of 90 %, with MIBI correctly predicting ectopic glands best in the thymus, mediastinum, or the retroesophageal space, and US was most accurate at detecting intrathyroidal glands.
Conclusions
Based on the data available at our institution, MIBI has a higher sensitivity than US in correctly localizing ectopic parathyroid adenomas, but the accuracy of detection varies based on location. Both imaging techniques have a high PPV for detecting an ectopic gland. Therefore, imaging with MIBI and US can be complementary, and positive localization of an ectopic gland with either modality is highly accurate and can facilitate a more focused surgical approach.
Gamma secretase inhibitors (GSIs), initially developed as Alzheimer's therapies, have been repurposed as anticancer agents given their inhibition of Notch receptor cleavage. The success of GSIs in ...preclinical models has been ascribed to induction of cancer stem‐like cell differentiation and apoptosis, while also impairing epithelial‐to‐mesenchymal transition and sensitizing cells to traditional chemoradiotherapies. The promise of these agents has yet to be realized in the clinic, however, as GSIs have failed to demonstrate clinical benefit in most solid tumors with the notable exceptions of CNS malignancies and desmoid tumors. Disappointing clinical performance to date reflects important questions that remain to be answered. For example, what is the net impact of these agents on antitumor immune responses, and will they require concurrent targeting of tumor‐intrinsic compensatory pathways? Addressing these limitations in our current understanding of GSI mechanisms will undoubtedly facilitate their rational incorporation into combinatorial strategies and provide a valuable tool with which to combat Notch‐dependent cancers. In the present review, we provide a current understanding of GSI mechanisms, discuss clinical performance to date, and suggest areas for future investigation that might maximize the utility of these agents.
Implications for Practice
The performance of gamma secretase inhibitors (GSIs) in clinical trials generally has not reflected their encouraging performance in preclinical studies. This review provides a current perspective on the clinical performance of GSIs across various solid tumor types alongside putative mechanisms of antitumor activity. Through exploration of outstanding gaps in knowledge as well as reasons for success in certain cancer types, the authors identify areas for future investigation that will likely enable incorporation of GSIs into rational combinatorial strategies for superior tumor control and patient outcomes.
This review focuses on the current understanding of gamma secretase inhibitors (GSI), as well as clinical performance to date and areas for future investigation that might maximize the utility of these agents.
Background
In papillary thyroid cancer, the role of lymph node dissection remains controversial, and staging systems consider metastatic lymph nodes as a binary entity. The purpose of this study was ...to determine a threshold lymph node ratio (LNR) that impacted disease-specific mortality (DSM).
Methods
We utilized the surveillance, epidemiology, and end results (SEER) database to analyze adult patients who underwent thyroidectomy with lymph node dissection. A LNR (metastatic lymph nodes to total lymph nodes) was calculated after eliminating patients with less than three nodes collected. Kaplan–Meier estimates for DSM were plotted for LNRs and compared by the log rank test. The Cox proportional hazards model was used to evaluate LNR with other known clinical and pathologic determinants of prognosis.
Results
A total of 10,955 cases contained data on lymph nodes. Median follow-up time was 25 months (range 0–59 months), and the mean LNR was 0.28 ± 0.37. After comparing Kaplan–Meier survival estimates and overall DSM rates, we found that a LNR ≥0.42 best divided those with lymph node metastasis based on DSM (
p
< 0.01). Those with a LNR ≥0.42 experienced a DSM rate of 1.72 % while those with a LNR <0.42 had a DSM rate of 0.65 % (
p
< 0.01). In addition, patients with a LNR ≥0.42 experienced a 77 % higher DSM rate compared to those with metastatic lymph nodes as a whole. When considered with other known determinants of prognosis, we found that LNR was strongly associated with DSM (hazard ratio 4.33, 95 % confidence interval 1.68–11.18,
p
< 0.01).
Conclusions
LNR is a strong determinant of DSM, and a threshold LNR of 0.42 can be used to risk-stratify patients with metastatic lymph nodes.
The Role of Notch3 in Cancer Aburjania, Zviadi; Jang, Samuel; Whitt, Jason ...
The oncologist (Dayton, Ohio),
August 2018, Letnik:
23, Številka:
8
Journal Article
Recenzirano
Odprti dostop
The Notch family is a highly conserved gene group that regulates cell‐cell interaction, embryogenesis, and tissue commitment. This review article focuses on the third Notch family subtype, Notch3. ...Regulation via Notch3 signaling was first implicated in vasculogenesis. However, more recent findings suggest that Notch3 signaling may play an important role in oncogenesis, tumor maintenance, and resistance to chemotherapy. Its role is mainly oncogenic, although in some cancers it appears to be tumor suppressive. Despite the wealth of published literature, it remains relatively underexplored and requires further research to shed more light on its role in cancer development, determine its tissue‐specific function, and elaborate novel treatment strategies. Herein we summarize the role of Notch3 in cancer, possible mechanisms of its action, and current cancer treatment strategies targeting Notch3 signaling.
Implications for Practice
The Notch family is a highly conserved gene group that regulates cell‐cell interaction, embryogenesis, and tissue commitment. This review summarizes the existing data on the third subtype of the Notch family, Notch3. The role of Notch3 in different types of cancers is discussed, as well as implications of its modification and new strategies to affect Notch3 signaling activity.
This review article focuses on the Notch3 gene subtype, summarizing its role in cancer, possible mechanisms of its action, and current cancer treatment strategies targeting Notch3 signaling.
Neuroendocrine Tumors of the Stomach Corey, Britney; Chen, Herbert
The Surgical clinics of North America,
04/2017, Letnik:
97, Številka:
2
Journal Article
Recenzirano
Gastric neuroendocrine tumors (NETs) are classified into three types. Type I gastric NETs are associated with chronic atrophic gastritis. They have a good prognosis and endoscopic resection is the ...mainstay of treatment. Type II gastric NETs are caused by hypergastrinemia. They have a poorer prognosis, and resection is required to control the disease. Endoscopic versus surgical resection is recommended for the gastric lesion. Type III gastric NETs are sporadic and not associated with any specific condition. They have the worst prognosis with the highest rate of metastatic disease, and oncologic resection is recommended. Medical therapies have some role.
PDF
