The increasing popularity of the dihydrouracil motif in cereblon (CRBN) recruiting proteolysis-targeting chimeras (PROTACs) has necessitated the development of a facile, cost-effective, and high-yielding method for its introduction into molecules. To that end, we disclose herein an N-1 selective Pd-catalyzed cross-coupling of dihydrouracil with aryl electrophiles to provide access to medicinally relevant scaffolds in a single step. This approach exhibits excellent functional group tolerance and broad applicability to an abundance of (hetero)aryl halides and phenol derivatives and utilizes readily available catalyst/ligand systems.
View Article and Find Full Text PDFEur Arch Otorhinolaryngol
October 2024
Soft tissue sarcomas (STS), comprising approximately 1% of adult solid malignancies, are primarily treated with surgery, with the choice of perioperative treatment being a challenging and highly individualized decision. Clinical trials assessing neoadjuvant modalities in STS predominantly use clinical outcomes or radiologic response as endpoints, with pathologic complete response (pCR) not being employed as a designated study endpoint. Our systematic review aimed to assess the rates of pCR in clinical trials of different neoadjuvant modalities for STS and its correlation with patient clinical outcomes.
View Article and Find Full Text PDFSoft tissue sarcomas (STS) are rare tumours arising in mesenchymal tissues and can occur almost anywhere in the body. Their rarity, and the heterogeneity of subtype and location, means that developing evidence-based guidelines is complicated by the limitations of the data available. This makes it more important that STS are managed by expert multidisciplinary teams, to ensure consistent and optimal treatment, recruitment to clinical trials, and the ongoing accumulation of further data and knowledge.
View Article and Find Full Text PDFBackground: Iatrogenic injury of the parathyroid glands is the most frequent complication after total thyroidectomy.
Objective: To determine the effectiveness of near-infrared autofluorescence (NIRAF) in reducing postoperative hypocalcemia following total thyroidectomy.
Methods: PubMed, Scopus, and Google Scholar databases were searched.
Poorly differentiated thyroid carcinomas (PDTC) are rare diseases; nevertheless, they account for the majority of deaths from non-anaplastic follicular cell-derived thyroid carcinomas. Establishing the diagnosis and treatment of PDTC is challenging given the low incidence and the lack of standardization of diagnostic criteria. These limitations hamper the ability to compare therapeutic modalities and outcomes between recent and older studies.
View Article and Find Full Text PDFImmunoglobulin G4-related disease (IgG4-RD) is a multi-organ disorder characterized by a highly variable clinical presentation depending on the affected organ/s, extent of tumefactive fibroinflammatory lesions, and associated functional impairment. The disease pursues a chronic, relapsing, often asymptomatic course and hence may pose a significant diagnostic challenge. Diagnostic delay can lead to progressive fibrosis and irreversible organ damage resulting into significant morbidity and even mortality.
View Article and Find Full Text PDFAims: Phyllodes tumours and breast sarcomas are uncommon tumours and their rarity poses significant challenges in diagnosis and management. This cross-sectional study was conducted to evaluate the multidisciplinary clinical practice for these tumours across the UK and Ireland, with the aim of identifying gaps in knowledge and providing direction for establishing national guidelines.
Materials And Methods: An international survey was adapted and circulated to breast and/or sarcoma surgeons and oncologists in the UK and Ireland through national organisations.
J Laryngol Otol
January 2024
Objective: This study investigates the impact of primary care utilisation of a symptom-based head and neck cancer risk calculator (Head and Neck Cancer Risk Calculator version 2) in the post-coronavirus disease 2019 period on the number of primary care referrals and cancer diagnoses.
Methods: The number of referrals from April 2019 to August 2019 and from April 2020 to July 2020 (pre-calculator) was compared with the number from the period January 2021 to August 2022 (post-calculator) using the chi-square test. The patients' characteristics, referral urgency, triage outcome, Head and Neck Cancer Risk Calculator version 2 score and cancer diagnosis were recorded.
Background: The updated 2014 BTA guidelines emphasised a more conservative, risk adapted model for the management of low-risk differentiated thyroid cancer (DTC). In comparison to historical approach of total thyroidectomy combined with radioactive iodine, treatment de-escalation is increasingly supported.
Aims: To evaluate the impact of the updated BTA guidelines on the management of DTC cases at regional UK centre.
Thyroid and parathyroid surgery requires careful dissection around the vascular pedicle of the parathyroid glands to avoid excessive manipulation of the tissues. If the blood supply to the parathyroid glands is disrupted, or the glands are inadvertently removed, temporary and/or permanent hypocalcemia can occur, requiring post-operative exogenous calcium and vitamin D analogues to maintain stable levels. This can have a significant impact on the quality of life of patients, particularly if it results in permanent hypocalcemia.
View Article and Find Full Text PDFDifferentiated thyroid carcinomas (DTC) have an excellent prognosis, but this is sometimes overshadowed by tumor recurrences following initial treatment (approximately 15% of cases during follow-up), due to unrecognized disease extent at initial diagnosis or a more aggressive tumor biology, which are the usual risk factors. The possible sites of recurrence are local, regional, or distant. Local and regional recurrences can usually be successfully managed with surgery and radioiodine therapy, as are some isolated distant recurrences, such as bone metastases.
View Article and Find Full Text PDFBackground: Decision-making in the management of patients with retroperitoneal sarcoma is complex and requires input from a number of different specialists. The aim of this study was to evaluate the levels of agreement in terms of resectability, treatment allocation, and organs proposed to be resected across different retroperitoneal sarcoma multidisciplinary team meetings.
Methods: The CT scans and clinical information of 21 anonymized retroperitoneal sarcoma patients were sent to all of the retroperitoneal sarcoma multidisciplinary team meetings in Great Britain, which were asked to give an opinion about resectability, treatment allocation, and organs proposed to be resected.
We present a thorough review of the literature on Riedel thyroiditis (RT) with emphasis on aetiology, diagnosis and management, using the PubMed, Sinomed, and China National Knowledge Infrastructure databases. Although the exact aetiology of RT remains obscure, the histopathological features are consistent with a localized form of IgG-related systemic disease (IgG-RSD). Nevertheless, IgG4-RSD as a systemic fibroinflammatory disorder per se rarely affects the thyroid in the context of multiorgan manifestations.
View Article and Find Full Text PDFBackground: The British Thyroid Association and American Thyroid Association guideline definitions for low-risk differentiated thyroid cancers are susceptible to differing interpretations, resulting in different clinical management in the UK.
Objective: To explore the national effect of these guidelines on the management of low-risk differentiated thyroid cancers.
Methods: Anonymised questionnaires were sent to multidisciplinary teams performing thyroidectomies in the UK.
Adequate pain control enhances patients' quality of life and allows a quick return to normal activities. Current pain management practices may contribute to the crisis of opioid addiction. We summarize the evidence that evaluates locoregional interventions to decrease pain and neck discomfort after thyroidectomy.
View Article and Find Full Text PDFAim: Multifocality is a frequent feature of papillary thyroid carcinoma (PTC). Its prognostic value is controversial although national guidelines recommend treatment intensification if present. However, multifocality is not a binary but discrete variable.
View Article and Find Full Text PDFObjective: Primary surgical resection remains the mainstay of management in locally advanced differentiated thyroid cancer. Tyrosine kinase inhibitors have recently shown promising results in patients with recurrent locally advanced differentiated thyroid cancer. This study discussed four patients with locally advanced differentiated thyroid cancer managed with tyrosine kinase inhibitors used prior to surgery in the 'neoadjuvant' setting.
View Article and Find Full Text PDFVitamin D (VitD) deficiency has garnered significant attention in contemporary medical research. Although the canonical biological activity of VitD manifests itself mainly in the regulation of calcium-phosphorus metabolism, recent studies show that, thanks to the presence of numerous receptors, VitD may also play an important role in regulating the immune system. VitD deficiency has been demonstrated to impact autoimmune disease, coeliac disease, infections (including respiratory/COVID-19), and patients with cancer.
View Article and Find Full Text PDFLymph node metastases in non-well differentiated thyroid cancer (non-WDTC) are common, both in the central compartment (levels VI and VII) and in the lateral neck (Levels II to V). Nodal metastases negatively affect prognosis and should be treated to maximize locoregional control while minimizing morbidity. In non-WDTC, the rate of nodal involvement is variable and depends on the histology of the tumor.
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