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Endocrine Malignancies: Current Surgical Therapeutic Approaches

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Endocrinology & Metabolism".

Deadline for manuscript submissions: closed (25 October 2024) | Viewed by 9817

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Dr. Mariarita Tarallo

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Department of Surgery "Pietro Valdoni", Sapienza University of Rome, Rome, Italy
Interests: general and colorectal surgery; laparoscopy; robotic surgery
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Enrico Fiori

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Dear Colleagues,

Thyroid cancer (TC) is the most common endocrine neoplasia and is known to have a favorable prognosis. Nevertheless, differentiated thyroid cancer has the potential to be metastatic and poorly differentiated thyroid cancer can present at an advanced clinical stage upon initial observation. This makes it difficult to assess the clinical characteristics and treatment outcomes after surgical intervention, and these patients subsequently have a low survival rate. Various diagnostic and treatment methodologies are currently being trialed to overcome these limitations and efforts are being made to improve both the patient's prognosis and outcome.

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy and has a historically poor prognosis. Adjuvant therapy with mitotane, either alone or in combination with chemotherapy, is the standard of care treatment for ACC. Nevertheless, surgery remains the first line of curative treatment. Recently, several drugs targeting new pathways, such as insulin growth factor 2 (IGF2), beta-catenin pathway, and others, have entered clinical trials. Immunotherapy has also recently emerged as an important therapeutic option for several cancer models; however, the role of immunotherapy in the treatment cascade is not yet clear. Despite the recent advances in the development of novel treatment methods, ACC still has a poor prognosis.

This Special Issue encourages the submission of research articles which address how the pathophysiology of endocrine malignancy development drives both the current and novel emerging therapies that can be of benefit to patients, in addition to the refinement and advancement of surgical interventions. It is intended to present and discuss all the aspects of the currently available diagnostic and treatment methodologies, both surgical and non-surgical, of thyroid and adrenal malignancies via original research articles and reviews. For this Special Issue, we invite authors and researchers to publish original research and reviews highlighting the advancements in the diagnosis, prognosis, surgery, and therapeutics of endocrine malignancies, in particular, thyroid and adrenocortical cancer.

Potential topics may include, but are not limited to:

Thyroid cancer diagnosis and differentiation.
Clinical management and surgical treatment of TC patients.
Parathyroid pathologies: clinical and surgical management.
Adrenocortical cancer diagnosis: genetic, clinical, and radiological findings.
New pathways, targeted drugs, and immunotherapy for ACC patients.
Clinical management and surgical treatment of ACC patients.
Multiple endocrine neoplasia, genetic correlations, and therapeutic approaches.

Dr. Mariarita Tarallo
Prof. Dr. Enrico Fiori
Guest Editors

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

endocrine malignancies
thyroid cancer
adrenocortical cancer
parathyroid
men

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Related Special Issue

Endocrine Malignancies: Current Surgical Therapeutic Approaches: 2nd Edition in Journal of Clinical Medicine

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Research

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9 pages, 506 KiB

Open AccessArticle

The Application of Intermittent Intraoperative Neuromonitoring (I-IONM) and Continuous Intraoperative Neuromonitoring (C-IONM) During Thyroid Surgery: A Single-Center Study

by Bruno Cirillo, Gioia Brachini, Giuseppe Cavallaro, Mariarita Tarallo, Cecilia Carlino, Giulia Duranti, Martina Zambon, Andrea Mingoli, Luigi Simonelli and Marco Bononi

J. Clin. Med. 2025, 14(8), 2612; https://doi.org/10.3390/jcm14082612 - 10 Apr 2025

Viewed by 332

Abstract

Background: The application of intermittent intraoperative neuromonitoring (I-IONM) and continuous intraoperative neuromonitoring (C-IONM) has been widely accepted to improve surgical outcomes after thyroid surgery. This observational study aimed to evaluate the impact of vocal cord paralysis (VCP) in thyroid surgery conducted with I-IONM and C-IONM. Materials and Methods: From January 2018 to December 2022, 147 patients operated on with I-IONM and C-IONM for thyroid surgery were analyzed. Variations in the rates of the occurrence of temporary and permanent vocal cord paralysis between the two groups were compared. A p-value < 0.05 was considered statistically significant. Results: In total, 147 patients were eligible for inclusion in the study. Of these, 96 (65%) patients underwent thyroid surgery with I-IONM, 52 patients (35%) underwent surgery with C-IONM by a single surgeon. The percentage of temporary VCP was 4.1% (4 patients) in the I-IONM group; no patients had permanent VCP. In the C-IONM group, two patients (3.9%) had permanent vocal cord paralysis, and temporary vocal cord paralysis was observed in other two patients (3.9%), who recovered their nerve function after speech therapy. No statistically significant differences were found in the two groups. Conclusions: In our study, both I-IONM and C-IONM proved effective in predicting VCP, and no significant differences were observed between the two techniques in our series. Full article

(This article belongs to the Special Issue Endocrine Malignancies: Current Surgical Therapeutic Approaches)

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11 pages, 636 KiB

Open AccessArticle

Prevalence and Clinical Risk Factors of Thyroid Cancer in Retrosternal Goiter: A Retrospective Comparative Study with Cervical Multinodular Goiter

by Francesco Paolo Prete, Giuseppe Massimiliano De Luca, Lucia Ilaria Sgaramella, Alessandro Pasculli, Giovanna Di Meo, Carlotta Testini, Giuliana Rachele Puglisi, Matteo Rugge, Angela Gurrado and Mario Testini

J. Clin. Med. 2025, 14(2), 489; https://doi.org/10.3390/jcm14020489 - 14 Jan 2025

Viewed by 979

Abstract

Background: Surgical intervention in asymptomatic retrosternal goiter (RSG) is debated in the absence of suspicious cytology, while performing fine-needle aspiration (FNA) is challenging in thyroids with mediastinal extension. The rate of unexpected thyroid cancers found at the time of thyroidectomy varies widely, while the notion of increased cancer incidence in RSG with respect to cervical goiters is still controversial. Methods: We retrospectively reviewed 411 patients with a preoperative diagnosis of multinodular goiter (MNG) (114 retrosternal, 297 cervical) who underwent thyroidectomy at an academic endocrine surgery referral center between January 2019 and October 2022. Rates of cancer detected on the final pathology examination, overall and not anticipated by preoperative workup, were compared between cervical MNG (cMNG) and RSG. Results: Patients with RSG were older (58.2% vs. 50.6%; p < 0.001) and more likely to be men (34.2% vs. 23%; p = 0.014). Overall, thyroid cancer was found in 49.5% of cMNG specimens and in 35.1% of RSGs (p = 0.02), and cancer > 1 cm was found in 37.4% of cMNG and 17.4% of RSG (p = 0.003). Prevalence of unexpected thyroid cancer was not significantly different between cMNGs (29.8%) and RSGs (28.8%). Unexpected carcinomas > 1 cm impacted 11% of all RSGs. Conclusions: In this study, the prevalence of unexpected thyroid cancer in RSG was similar to cMNG and significant from a clinical standpoint, with 1 in every 10 RSG diagnosed with differentiated cancer > 1 cm. Findings may be partially attributed to the difficulty in performing FNA in the mediastinum. Surgeons should counsel patients preoperatively regarding the risk of unexpected thyroid cancer to set appropriate expectations of outcome. Full article

(This article belongs to the Special Issue Endocrine Malignancies: Current Surgical Therapeutic Approaches)

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15 pages, 1722 KiB

Open AccessArticle

A Machine Learning-Based Model for Preoperative Assessment and Malignancy Prediction in Patients with Atypia of Undetermined Significance Thyroid Nodules

by Gilseong Moon, Jae Hyun Park, Taesic Lee and Jong Ho Yoon

J. Clin. Med. 2024, 13(24), 7769; https://doi.org/10.3390/jcm13247769 - 19 Dec 2024

Viewed by 663

Abstract

Objectives: The aim of this study was to investigate the preoperative clinical and hematologic variables, including the neutrophil-to-lymphocyte ratio (NLR), that can be used to predict malignancy in patients with atypia of undetermined significance (AUS) thyroid nodules; we further aimed to develop a machine learning-based prediction model. Methods: We enrolled 280 patients who underwent surgery for AUS nodules at the Wonju Severance Christian Hospital between 2018 and 2022. A logistic regression-based model was trained and tested using cross-validation, with the performance evaluated using metrics such as the area under the receiver operating characteristic curve (AUROC). Results: Among the 280 patients, 116 (41.4%) were confirmed to have thyroid malignancies. Independent predictors of malignancy included age, tumor size, and the Korean Thyroid Imaging Reporting and Data System (K-TIRADS) classification, particularly in patients under 55 years of age. The addition of NLR to these predictors significantly improved the malignancy prediction accuracy in this subgroup. Conclusions: Incorporating NLR into preoperative assessments provides a cost-effective, accessible tool for refining surgical decision making in younger patients with AUS nodules. Full article

(This article belongs to the Special Issue Endocrine Malignancies: Current Surgical Therapeutic Approaches)

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15 pages, 1421 KiB

Open AccessArticle

Prevalence of Neoplasms in Patients with Acromegaly—A Single-Center Polish Study

by Martyna Strzelec, Małgorzata Rolla, Justyna Kuliczkowska-Płaksej, Marcin Kałużny, Natalia Słoka, Jakub Wronowicz, Marek Bolanowski and Aleksandra Jawiarczyk-Przybyłowska

J. Clin. Med. 2024, 13(22), 6847; https://doi.org/10.3390/jcm13226847 - 14 Nov 2024

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Abstract

Background/Objectives: Neoplasms are one of the three most common causes of death in patients with acromegaly. Our study aimed to assess the incidence of benign and malignant neoplasms among patients with acromegaly and the associations between this prevalence and the disease activity, the time of acromegaly diagnosis, and the time of its first symptoms. The correlation between neoplasm occurrence and pituitary somatotropic axis hormone levels was also studied, and the prevalence of different types of neoplasms was compared between the patients with acromegaly and the Polish population. Methods: A retrospective study included a statistical analysis of the medical documentation of 230 patients with acromegaly diagnosed and treated in the Department of Endocrinology, Diabetes, and Isotope Therapy in Wrocław (Poland) between 1976 and 2023. Results: We observed 171 cases of neoplasms (144 benign and 27 malignant). All types of neoplasms and benign tumors were diagnosed more frequently, in both the short and long term, after a diagnosis of acromegaly, but, after a long time, only malignant neoplasms were more frequently diagnosed. In the cases of controlled acromegaly, all types of neoplasms and benign neoplasms were more common than in cases of cured acromegaly. The incidence of neoplasms was higher, regardless of type, in patients with active acromegaly compared to the cured disease. Malignant neoplasms of the thyroid, renal, and stomach type were more common among our subjects compared to the Polish population. Conclusions: This study confirms the association between acromegaly, as well as its activity level and the time from its diagnosis, and the prevalence of neoplasms. Full article

(This article belongs to the Special Issue Endocrine Malignancies: Current Surgical Therapeutic Approaches)

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Review

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12 pages, 629 KiB

Open AccessReview

The Role of Radioiodine Therapy in Differentiated Thyroid Cancer Arising from Struma Ovarii: A Systematic Review

by Pietro Bellini, Francesco Dondi, Valentina Zilioli, Elisa Gatta, Maria Cavadini, Carlo Cappelli, Gian Luca Viganò and Francesco Bertagna

J. Clin. Med. 2024, 13(24), 7729; https://doi.org/10.3390/jcm13247729 - 18 Dec 2024

Viewed by 765

Abstract

Background: Struma ovarii (SO) is an ovarian teratoma with the presence of ectopic thyroid tissue. Differentiated thyroid cancer (DTC) in SO is a rare finding. Management of DTC in SO is currently not clearly established. We performed a systematic review of the literature to assess the role of 131I radiometabolic therapy in the treatment of DTC in SO. Methods: a wide literature search in the Scopus, PubMed/MEDLINE, and Web of Science databases was made to find published articles regarding the treatment of patients with DTC and SO. The quality assessment of studies was performed by QUADAS-2 evaluation. Results: eleven studies were included in the systematic review. All of them were retrospective studies and/or case series, and two of them also included a review of the literature. Most of the studies describe cases of DTC in SO treated by total thyroidectomy (TT) and subsequent radioiodine (RAI) therapy, especially in patients with distant metastases and/or concomitant thyroid cancer. However, the majority of patients apparently did not require radiometabolic therapy. Conclusions: TT and subsequent RAI therapy is usually performed in metastatic disease, not recommended in patients with intraovarian disease without risk factors, and it appeared possible but not mandatory in patients with risk factors. Full article

(This article belongs to the Special Issue Endocrine Malignancies: Current Surgical Therapeutic Approaches)

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33 pages, 800 KiB

Open AccessReview

Osteoporosis and Normocalcemic Primary Hyperparathyroidism (Conservatively or Surgically Managed)

by Ana-Maria Gheorghe, Claudiu Nistor, Aurelian-Emil Ranetti, Adrian Ciuche, Mihai-Lucian Ciobica, Mihaela Stanciu, Denisa Tanasescu, Florina Ligia Popa and Mara Carsote

J. Clin. Med. 2024, 13(21), 6325; https://doi.org/10.3390/jcm13216325 - 23 Oct 2024

Viewed by 1485

Abstract

Asymptomatic primary hyperparathyroidism (PHPT) involves 80–90% of the parathyroid tumor-associated cases of PHPT in the modern medical era, while normocalcemic PHPT (NPHPT) has a prevalence of 0.1–11%. We aimed to analyze the bone status and mineral metabolism in NPHPT amid conservative or surgical management. In this narrative review, we searched PubMed (between January 2020 and July 2024) via different keywords. Fourteen studies from the final analysis (388 patients with NPHPT; 1188 with PHPT; and 803 controls) showed that mean serum calcium levels varied between 2.57 and 2.26 mmol/L in NPHPT. Ten studies identified a similar 24 h urinary calcium in NPHPT versus hypercalcemic PHPT (HPHPT). Except for one study, a mandatory vitamin D analysis was performed, but the 25-hydroxyvitamin D cut-offs varied. Osteoporosis (n = 6 studies; N = 172 with NPHPT) was confirmed in 41.7–100% of NPHPT subjects. In surgery candidates, this rate might be overestimated. A DXA analysis was performed in eight studies (235 subjects with NPHPT, and 455 patients with HPHPT); two studies identified a lower BMD in HPHPT < NPHPT, but the results were not homogenous. A single study analyzed the TBS and found similar results in NPHPT. The prevalence of fractures (n = 9) varied between 7.4% and 42.8% in NPHPT. Bone turnover markers (N = 262 patients, n = 8 studies) showed lower bone formation markers in NPHPT versus PHPT (n = 3). Two studies analyzed the BMD and bone turnover markers following parathyroidectomy (161 patients, including 30 patients with NPHPT; mean ages over 60 years). To conclude, given the wide spectrum of complications associated with PHPT, an early diagnosis and proper management is essential. A more extensive screening in patients with osteoporosis and kidney stones might lead to the discovery of NPHPT, a more recently described form of PHPT. While it is still unclear whether NPHPT is an early stage of HPHPT or a separate entity, recent findings show similar osteoporosis and fracture occurrence, and an improvement in bone metabolism, following parathyroidectomy. More extensive prospective studies are crucial to understand the natural course of the disease, to reach a consensus regarding parathyroidectomy indications and surgery candidates’ selection, and to ensure proper personalized management for these patients. With the evolving diagnosis methods, PHPT has become a condition with a changing clinical presentation, which now requires modern evaluation and treatment approaches. Full article

(This article belongs to the Special Issue Endocrine Malignancies: Current Surgical Therapeutic Approaches)

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18 pages, 1394 KiB

Open AccessFeature PaperReview

Detection of the BRAF^V600E Mutation in Circulating Free Nucleic Acids as a Biomarker of Thyroid Cancer: A Review

by Emilia Niedziela, Łukasz Niedziela, Aldona Kowalska and Artur Kowalik

J. Clin. Med. 2024, 13(18), 5396; https://doi.org/10.3390/jcm13185396 - 12 Sep 2024

Cited by 1 | Viewed by 1701

Abstract

Background: Liquid biopsy is a method that could potentially improve the management of thyroid cancer (TC) by enabling the detection of circulating tumor DNA and RNA (ctDNA, ctRNA). The BRAF^V600E mutation appears to be the most representative example of a biomarker in liquid biopsy, as it is the most specific mutation for TC and a target for molecular therapeutics. The aim of this review is to summarize the available data on the detection of the BRAF^V600E mutation in liquid biopsy in patients with TC. Methods: A comprehensive analysis of the available literature on the detection of the BRAF^V600E mutation in liquid biopsy in TC was performed. Thirty-three papers meeting the inclusion criteria were selected after full-text evaluation. Results: Eleven papers discussed correlations between BRAF mutation and clinicopathological characteristics. Nine studies tested the utility of BRAF^V600E detection in the assessment of residual or recurrent disease. Seven studies investigated BRAF-mutated circulating tumor nucleic acids (ctNA) as a marker of response to targeted therapy. In seven studies the method did not detect the BRAF^V600E mutation. Conclusions: This review shows the potential of BRAF^V600E-mutated ctNA detection in monitoring disease progression, particularly in advanced TC. The diagnostic value of BRAF^V600E-mutated ctNA detection appears to be limited to advanced TC. The choice of the molecular method (quantitative PCR [qPCR], droplet digital polymerase chain reaction [ddPCR], and next-generation sequencing [NGS]) should be made based on the turnaround time, sensitivity of the test, and the clinical indications. Despite the promising outcomes of some studies, there is a need to verify these results on larger cohorts and to unify the molecular methods. Full article

(This article belongs to the Special Issue Endocrine Malignancies: Current Surgical Therapeutic Approaches)

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Other

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8 pages, 561 KiB

Open AccessBrief Report

Incidence and Clinical Relevance of Incidental Papillary Carcinoma in Thyroidectomy for Multinodular Goiters

by Aldo Bove, Roberto Manunzio, Gino Palone, Raffaella Marina Di Renzo, Giulia Valeria Calabrese, David Perpetuini, Mirko Barone, Stella Chiarini and Felice Mucilli

J. Clin. Med. 2023, 12(8), 2770; https://doi.org/10.3390/jcm12082770 - 7 Apr 2023

Cited by 2 | Viewed by 1996

Abstract

Introduction: Patients undergoing a total thyroidectomy for multinodular goiter typically have a long clinical history of the disease. They often come to surgery for compression symptoms, with no suspicion of neoplastic disease. For these patients, the incidence of microcarcinomas is high, even though we know that this does not affect subsequent therapies and long-term survival. On the other hand, when a true incidental carcinoma is present, the patient requires specific therapy and long-term follow-up. The purpose of the study was to identify the incidence of incidental carcinomas in the high prevalence region of goiter, the clinical-pathological characteristics of the tumor, and the therapeutic implications. Method: This is a retrospective study, from January 2010 to December 2020, on a case series of 1435 total thyroidectomies for goiters. All patients had a preoperative diagnosis of a benign disease. Gender, mean age, and mean duration from the initial diagnosis of goiter were evaluated along with the number and frequency of fine needle aspirations carried out. On the basis of the histological examination, the incidence of incidental carcinoma was then assessed (diameter ≥ 10 mm) as well as the incidence of microcarcinoma (diameter < 10 mm), the pathological characteristics (multifocality, capsular invasion), and the subsequent prescribed therapies. Results: Patients with incidental carcinoma numbered 41 (2.8%%), 34 women and 7 men. The mean age was 53.5 years, while the patients diagnosed with microcarcinoma were 88 (6.1%). The mean duration of the disease from initial diagnosis was 7.8 years. On average, these patients underwent 1.8 fine needle aspirations during the course of the disease, almost exclusively in the first four years. The mean diameter of the tumor was 1.35 cm (±0.3). Multifocality was present in six patients, while only one patient presented capsular invasion. The chi-square test delivered a significant dependence on gender in terms of the incidental diagnosis after Yates correction (chi-stat = 5.064; p = 0.024), highlighting a higher incidence in the female population. All patients underwent subsequent metabolic radiotherapy. The mean follow-up was 6.3 years and in the 35 patients examined, none displayed any recurrence of the disease. Conclusions: Incidental carcinoma is not uncommon in patients who have undergone total thyroidectomy for goiters. It must be differentiated from microcarcinoma for its therapeutic implications and the follow-up of the patient. Statistical analysis has shown that the only significant variable is gender. In a goiter area, the careful monitoring of patients is required to highlight suspicious clinical–instrumental aspects that may appear even several years after the initial diagnosis. Full article

(This article belongs to the Special Issue Endocrine Malignancies: Current Surgical Therapeutic Approaches)

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