Initial surgical management of sporadic medullary thyroid cancer: Guidelines based optimal care - A systematic review.

INTRODUCTION: Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor from parafollicular cells that produce calcitonin (Ct). Despite several existing guidelines for the surgical management of sporadic MTC (sMTC), optimal initial surgical management of the thyroid, the central and the lateral neck remains a matter of debate. METHODS: A systematic review in PubMed and Scopus for current guidelines addressing the surgical management of sMTC and its referenced citations was conducted as per the PRISMA guidelines. RESULTS: Two-hundred and one articles were identified, of which 7 met the inclusion criteria. Overall, guidelines vary significantly in their recommendations for the surgical management of sMTC. Only one guideline recommended partial thyroidectomy for limited disease, but the possibility to avoid completion thyroidectomy in selected cases is acknowledged in 42% (3/7) of the remaining guidelines. The majority of guidelines (71.4%; 5/7) recommended prophylactic central neck dissection (CND) for all patients while the remaining two guidelines recommended CND based on Ct level and tumor size. The role of prophylactic lateral neck dissection based on preoperative Ct levels was recommended by 42% (3/7) of guidelines. Overall, these guidelines are based on low-quality evidence, mostly single-center retrospective series, some of which are over 20 years old. CONCLUSION: Current surgical management guidelines of sMTC should be revised, and ought to be based on updated data challenging current recommendations, which are based on historic, low-quality evidence. Partial thyroidectomy may become a viable option for small, limited tumors. Prospective, multi-center studies may be useful to conclude whether prophylactic ND is necessary in all sMTC patients.

Implication of surgical loupes on complications following thyroidectomy: a meta-analysis.

OBJECTIVE: To determine the effectiveness of surgical loupes in reducing postoperative RLN palsy and hypocalcemia following thyroidectomy. DATA SOURCES: PubMed, Scopus and Google Scholar databases were searched between 2000 and 2024. REVIEW METHODS: Studies were included if they reported at least one complication outcome following thyroidectomy using surgical loupes. The outcome measure was the log odds ratio, with negative log odds indicating results favouring the experimental group. The model utilized the DerSimonian-Laird estimator, and Wald-type tests. RESULTS: The qualitative data synthesis included 813 patients from 6 included studies, including 410 patients with surgical loupes and 403 patients without surgical loupes. There was a statistically significant reduction in the rate of temporary RLN palsy in the surgical loupe group log(OR) = - 0.87 [(- 1.58, - 0.15), DL (Dersimonian and Laird method), REM (random effects model), CI (confidence interval) = 95%], or a 41.8% lower probability. The rates of permanent RLN palsy log(OR) = - 0.31 [(- 1.45, 0.82), DL, REM, CI = 95%], temporary hypocalcemia log(OR) = - 0.34 [(- 1.25, 0.57), DL, REM, CI = 95%], and permanent hypocalcemia log(OR) = - 0.85 [(- 2.24, 0.54), DL, REM, CI = 95%] were not statistically significant between the two groups, although there were trends toward decreases in these rates in the loupes group. CONCLUSIONS: Surgical loupe use during thyroidectomy can lead to a 41.8% lower probability of temporary RLN palsy compared to operating without loupes. LEVEL OF EVIDENCE: 3a.

Current management of xerostomia in head and neck cancer patients.

Radiotherapy (RT) continues to play a key role in the management of head and neck cancer (HNC). Xerostomia remains a principal detriment to the quality of life (QoL) for 80 % of surviving patients receiving head and neck radiation. Radiation-induced injury to the salivary glands is dose-dependent, and thus efforts have been focused on decreasing radiation to the salivary glands. Decreased saliva production reduces both short-term and long-term quality of life in head and neck survivors by impacting on taste and contributing to dysphagia. Several radioprotective agents to the salivary gland have been investigated. Although not widely practiced, surgical transfer of the submandibular gland prior to RT is the mainstay of surgical options in preventing xerostomia. This review focuses on the strategies to improve xerostomia following radiation therapy in head and neck cancers.

Complications related to the Cook-Swartz implantable Doppler probe use in head and neck microvascular reconstruction: a systematic review.

PURPOSE: Vascular perfusion research has been dedicated to identify inexpensive, effective, and easy to use methods to assess free flap perfusion for both buried and non-buried flaps. METHODS: Systematic review of complications in patients underwent Head and Neck microsurgical reconstruction and vascular implantable Doppler monitoring. RESULTS: Sixteen articles were included for qualitative analysis. 2535 (92.2%) patients received IDP monitorization. Venous thrombosis was the most common vascular complication effecting 28 (1.1%). Regarding complications potentially related to the use of the IDP, just one study described the presence of granuloma formation along the suture line in 2 (0.07%) patients. CONCLUSIONS: Our findings indicated that Cook-Swartz IDP will represents a safe and effective device for FF monitoring in HN reconstructive micro-surgery. A detailed prospective registration of the results and complications related to the use of IDP remains mandatory to precisely estimate results, cost, and complications.

Iron, Ferroptosis, and Head and Neck Cancer.

Ferroptosis is an iron-dependent regulatory form of cell death characterized by the accumulation of intracellular reactive oxygen species and lipid peroxidation. It plays a critical role not only in promoting drug resistance in tumors, but also in shaping therapeutic approaches for various malignancies. This review aims to elucidate the relationship between ferroptosis and head and neck cancer treatment by discussing its conceptual framework, mechanism of action, functional aspects, and implications for tumor therapy. In addition, this review consolidates strategies aimed at improving the efficacy of head and neck cancer treatment through modulation of ferroptosis, herein serving as a valuable reference for advancing the treatment landscape for this patient population.

A NEW HYPOTHESIS IN THE TREATMENT OF RECURRENT GLIOBLASTOMA MULTIFORME (GBM). PART 1: INTRODUCTION.

Modern treatment of glioblastoma multiforme (GBM) is based on neurosurgical methods combined with radiotherapy and chemotherapy. The prognosis for patients with GBM is extremely poor. Often, complete removal of the tumor is impossible and it often recurs. Therefore, in addition to standard regimens, modern methods such as modulated electrohyperthermia, monoclonal antibodies and individualised multimodal immunotherapy (IMI) based on vaccines and oncolytic viruses are also used in the treatment of GBM. Radioiodine therapy (RIT) also holds out hope for an effective treatment of this extremely aggressive brain tumor. The expression of the sodium iodide symporter (NIS) gene has been proven to have a positive effect on the treatment of selected cancers. Research confirm the presence of expression of this gene in GBM cells, although only in animal studies. Is it possible and therapeutically effective to treat GBM with RIT without the use of an exogenous NIS gene? The safety of therapy is relevant, as the only more serious adverse effect may be hypothyroidism. The use of RIT requires further clinical studies in patients. Perhaps it is worth revolutionizing GBM therapy to give sufferers a "new life".

A NEW HYPOTHESIS IN THE TREATMENT OF RECURRENT GLIOBLASTOMA MULTIFORME (GBM). PART 2: IS THERE AN ALTERNATIVE THERAPY OPTION IN RECURRENT GM WHEN ALL STANDARD TREATMENTS HAVE BEEN EXHAUSTED?

Glioblastoma multiforme (GBM) is the most aggressive and malignant brain tumor. The average survival time for a patient diagnosed with GBM, using standard treatment methods, is several months. Besides the routinely applied treatments such as neurosurgery, radiotherapy, and chemotherapy, progress is being made in the field of oncology, offering hope for improved treatment outcomes. New treatment methods include individualized multimodal immunotherapy (IMI) and modulated electro-hyperthermia. The coauthor of the above series of articles (parts 1 and 2) - A.Cz. presents the concept of a new, potentially breakthrough treatment option for recurrent GBM. A.Cz. was diagnosed with GBM in August 2021. Exhaustion of standard treatment methods, as well as immunotherapy and virotherapy, only provided temporary relief. Unfortunately, after a few months, the disease recurred. Having little to lose, A.Cz. accepted an ablative dose of 2960 MBq (80 mCi) of I131, based on available literature data. Three days before the administration of radioiodine therapy (RIT), A.Cz. prophylactically blocked the thyroid's ability to absorb the radioisotope. In June 2023, approximately 7 weeks after receiving single I131 dose, the MRI examination confirmed a 30% reduction in the tumor's size. Based on this, one can speculate that Iodine-131 therapy may be an alternative treatment option for GBM patients in the future. However, this hypothesis requires confirmation in further clinical studies.

TP53 mutations in head and neck cancer.

Head and neck squamous cell carcinomas (HNSCCs) arising in the mucosal linings of the upper aerodigestive tract are highly heterogeneous, aggressive, and multifactorial tumors affecting more than half a million patients worldwide each year. Classical etiological factors for HNSCC include alcohol, tobacco, and human papillomavirus (HPV) infection. Current treatment options for HNSCCs encompass surgery, radiotherapy, chemotherapy, or combinatorial remedies. Comprehensive integrative genomic analysis of HNSCC has identified mutations in TP53 gene as the most frequent of all somatic genomic alterations. TP53 mutations are associated with either loss of wild-type p53 function or gain of functions that promote invasion, metastasis, genomic instability, and cancer cell proliferation. Interestingly, disruptive TP53 mutations in tumor DNA are associated with aggressiveness and reduced survival after surgical treatment of HNSCC. This review summarizes the current evidence and impact of TP53 mutations in HNSCC.

Revisiting the role of surgery in the treatment of Graves' disease.

Graves' disease (GD) can be managed by antithyroid drugs (ATD), radioactive iodine (RAI) and surgery. Thyroidectomy offers the highest success rates for both primary and persistent disease, yet it is the least recommended or utilized option reaching <1% for primary disease and <25% for persistent disease. Several surveys have found surgery to be the least recommended by endocrinologists worldwide. With the development of remote access thyroidectomies and intraoperative nerve monitoring of the recurrent laryngeal nerve, combined with current knowledge of possible risks associated with RAI or failure of ATDs, revaluation of the benefit to harm ratio of surgery in the treatment of GD is warranted. The aim of this review is to discuss possible reasons for the low proportion of surgery in the treatment of GD, emphasizing an evidence-based approach to the clinicians' preferences for surgical referrals, surgical indications and confronting traditional reasons and concerns relating to the low referral rate with up-to-date data.

Clear Cell Neoplasms of Salivary Glands: A Diagnostic Challenge.

This review focuses on the heterogenous group of clear cell neoplasms of salivary glands and attempts to identify major differential diagnostic features. Within the head and neck region, clear cells are found most commonly in salivary gland tumors, but may also be seen in tumors of squamous or odontogenic epithelial origin, primary or metastatic carcinomas, benign or malignant melanocytic lesions, or benign or malignant mesenchymal tumors. Clear cells occur fairly commonly among a wide variety of salivary gland neoplasms, but mostly they constitute only a minor component of the tumor cell population. Clear cells represent a major diagnostic feature in two salivary gland neoplasms, epithelial-myoepithelial carcinoma and hyalinizing clear cell carcinoma. In addition, salivary gland neoplasms composed predominantly of clear cells could also include clear cell variants of other salivary neoplasms, such as mucoepidermoid carcinoma and myoepithelial carcinoma, but their tumor type-specific histologic features may only be available in limited nonclear cell areas of the tumor. Diagnosing predominantly clear cell salivary gland tumors is difficult because the immunoprofiles and morphologic features may overlap and the same tumor entity may also have a wide range of other histologic presentations. Many salivary gland tumors are characterized by tumor type-specific genomic alterations, particularly gene fusions of the ETV6 gene in secretory carcinoma, the MYB and MYBL1 genes in adenoid cystic carcinoma, the MAML2 gene in mucoepidermoid carcinoma, the EWSR1 gene in hyalinizing clear cell carcinoma, and others. Thus, along with conventional histopathologic examination and immunoprofiling, molecular and genetic tests may be important in the diagnosis of salivary gland clear cell tumors by demonstrating genetic alterations specific to them.

Pleomorphic adenoma: the great mimicker of malignancy.

Pleomorphic adenoma (PA) is the most common salivary gland neoplasm, and its diagnosis is straightforward in the majority of cases. However, not infrequently, PA shows unusual and uncommon histological features that can be confused with those of malignancy. The difficulties in diagnosing PA arise from its ability to mimic invasion, show atypical or metaplastic cytomorphology, and show morphological features that overlap with those of established salivary gland carcinomas. In addition, recognising early malignant transformation to carcinoma ex-pleomorphic adenoma continues to be a frequent challenge. This review describes the diagnostic pitfalls of PA, and offers a systematic approach to avoid them by combining classic histopathology with novel immunohistochemical and molecular tests.

Emerging Entities and New Diagnostic Markers for Head and Neck Soft Tissue and Bone Tumors.

Bone and soft tissue tumors of the head and neck are relatively uncommon tumors that often represent a diagnostic challenge because of the wide range of entities that must be considered in the differential diagnosis. Over the past few years, classification of bone and soft tissue tumors has evolved primarily because of substantial contributions from molecular genetics, with the identification of new markers that are increasingly used to complement histopathologic findings in the routine diagnostic workup. This review focuses on the recently described mesenchymal tumors that preferentially involve the head and neck region, with a focus on the most relevant novel immunohistochemical and molecular findings, including gene fusions and mutations, that can help in the diagnosis and in the assessment of clinical behavior.

High-grade Transformation/Dedifferentiation in Salivary Gland Carcinomas: Occurrence Across Subtypes and Clinical Significance.

High-grade transformation (HGT) or dedifferentiation has been described in a variety of salivary gland carcinomas, including acinic cell carcinoma, secretory carcinoma, adenoid cystic carcinoma, epithelial-myoepithelial carcinoma, polymorphous adenocarcinoma, low-grade mucoepidermoid carcinoma, and hyalinizing clear cell carcinoma. High-grade (HG) transformed tumors are composed of a conventional low-grade component characterized by specific microscopic and immunohistochemical features for the given entity, intermingled with or juxtaposed to areas of HG morphology. This is usually either poorly differentiated adenocarcinoma, carcinoma not otherwise specified, or undifferentiated carcinoma, in which the original line of differentiation is lost. The HG component is composed of solid nests of anaplastic cells with large vesicular pleomorphic nuclei, prominent nucleoli, and abundant cytoplasm. Frequent mitoses and extensive necrosis may be present. The Ki-67 labeling index is consistently higher in the HG component. The molecular genetic mechanisms responsible for HGT of salivary gland carcinomas are largely unknown, though p53 inactivation and human epidermal growth factor receptor 2 overexpression and/or gene amplification have been demonstrated in the HG component in a few examples, the frequency varies for each histologic type. Salivary gland carcinomas with HGT are more aggressive than conventional carcinomas, with a higher local recurrence rate and a poorer prognosis. They have a high propensity for cervical lymph node metastasis suggesting a need for a wider resection and neck dissection. HGT of salivary gland carcinoma can occur either at initial presentation or less commonly at the time of recurrence, sometimes following postoperative radiotherapy. The potential for HGT in almost any type of salivary gland carcinoma warrants a thorough sampling of all salivary gland malignancies to prevent oversight of a HG component.

Transoral endoscopic vestibular approach for thyroidectomy and parathyroidectomy - From promise to practice.

OBJECTIVES: To describe the evolution and recent series on transoral endoscopic vestibular approach thyroidectomy and parathyroidectomy (TOET/PVA). DATA SOURCES: PubMed, Google Scholar. REVIEW METHODS: Review of the available English literature. RESULTS: TOET/PVA may offer several advantages over other remote access thyroidectomy approaches and has been adopted by many centers worldwide with excellent success rates. Indications include benign disease and early thyroid cancer patients. Complication rate is comparable to the trans-cervical approach. The suggested framework has been validated in recent studies and its feasibility confirmed. CONCLUSION: TOET/PVA has now been used to treat thousands of patients worldwide due to low cost, short learning curve and excellent cosmetic outcomes. Further studies will be necessary to demonstrate oncologic non-inferiority and also the true value that is added by the approach.

What is the role of sentinel lymph node biopsy in the management of oral cancer in 2020?

Approximately 70-80% of patients with cT1-2N0 oral squamous cell carcinoma (OSCC) ultimately prove to have no cancer in the cervical lymphatics on final pathology after selective neck dissection. As a result, sentinel lymph node biopsy (SLNB) has been adopted during the last decade as a diagnostic staging method to intelligently identify patients who would benefit from formal selective lymphadenectomy or neck irradiation. While not yet universally accepted, SLNB is now incorporated in many national guidelines. SLNB offers a less invasive alternative to elective neck dissection (END), and has some advantages and disadvantages. SLNB can assess the individual drainage pattern and, with step serial sectioning and immunohistochemistry (IHC), can enable the accurate detection of micrometastases and isolated tumor cells (ITCs). Staging of the neck is improved relative to END with routine histopathological examination. The improvements in staging are particularly notable for the contralateral neck and the pretreated neck. However, for floor of mouth (FOM) tumors, occult metastases are frequently missed by SLNB due to the proximity of activity from the primary site to the lymphatics (the shine through phenomenon). For FOM cancers, it is advised to perform either elective neck dissection or superselective neck dissection of the preglandular triangle of level I. New tracers and techniques under development may improve the diagnostic accuracy of SLNB for early-stage OSCC, particularly for FOM tumors. Treatment of the neck (either neck dissection or radiotherapy), although limited to levels I-IV, remains mandatory for any positive category of metastasis (macrometastasis, micrometastasis, or ITCs). Recently, the updated EANM practical guidelines for SLN localization in OSCC and the surgical consensus guidelines on SLNB in patients with OSCC were published. In this review, the current evidence and results of SLNB in early OSCC are presented.

Standardization for oncologic head and neck surgery.

The inherent variability in performing specific surgical procedures for head and neck cancer remains a barrier for accurately assessing treatment outcomes, particularly in clinical trials. While non-surgical modalities for cancer therapeutics have evolved to become far more uniform, there remains the challenge to standardize surgery. The purpose of this review is to identify the barriers in achieving uniformity and to highlight efforts by surgical groups to standardize selected operations and nomenclature. While further improvements in standardization will remain a challenge, we must encourage surgical groups to focus on strategies that provide such a level.

Sinonasal Undifferentiated Carcinoma (SNUC): From an Entity to Morphologic Pattern and Back Again-A Historical Perspective.

Since the first description of sinonasal undifferentiated carcinoma (SNUC) as a distinctive highly aggressive sinonasal neoplasm with probable origin from the sinonasal mucosa (Schneiderian epithelium), SNUC has been the subject of ongoing study and controversy. In particular, the SNUC category gradually became a "wastebasket" for any undifferentiated or unclassifiable sinonasal malignancy of definite or probable epithelial origin. However, with the availability of more specific and sensitive immunohistochemical antibodies and increasing implementation of novel genetic tools, the historical SNUC category became the subject of progressive subdivision leading to recognition of specific genetically defined, reproducible subtypes. These recently recognized entities are characterized by distinctive genetic aberrations including NUTM1-rearranged carcinoma (NUT carcinoma) and carcinomas associated with inactivation of different members of the SWI/SNF chromatin-remodeling gene complex such as SMARCB1-deficient and less frequently SMARCA4-deficient carcinoma. The ring became almost closed, with recent studies highlighting frequent oncogenic IDH2 mutations in the vast majority of histologically defined SNUCs, with a frequency of 82%. A review of these cases suggests the possibility that "true SNUC" probably represents a distinctive neoplastic disease entity, morphologically, phenotypically, and genetically. This review addresses this topic from a historical perspective, with a focus on recently recognized genetically defined subsets within the SNUC spectrum.

Value and Quality of Care in Head and Neck Oncology.

PURPOSE OF REVIEW: The concept of value-based health care (VBHC) was articulated more than a decade ago. However, its clinical implementation remains an on-going process and a particularly demanding one for the domain of head and neck cancer (HNC). These cancers often present with fast growing tumors in functionally and cosmetically sensitive sites and afflict patients with differing circumstances and comorbidity. Moreover, the various treatment modalities and protocols have different effects on functional outcomes. Hence, the interpretation of what constitutes VBHC in head and neck oncology remains challenging. RECENT FINDINGS: This monograph reviews developments in specific aspects of VBHC for HNC patients, including establishment of registries and quality indices (such as infrastructure, process, and outcome indicators). It emphasizes the importance of the multidisciplinary team, "time to treatment intervals," and adherence to guidelines. The discussion addresses major indicators including survival, quality of life and functional outcomes, and adverse events. Also, strengths and weaknesses of nomograms, prognostic and decision models, and variation of care warrant attention. Health care professionals, together with patients, must properly define quality and relevant outcomes, both for the individual patient as well as the HNC population. It is essential to capture and organize the relevant data so that they can be analyzed and the results used to improve both outcomes and value.

Vitamin D in Head and Neck Cancer: a Systematic Review.

PURPOSE OF REVIEW: Observational studies have shown that serum 25-OH vitamin D [25(OH)D] is inversely associated with overall cancer risk in many malignancies. We performed a systematic literature review to determine whether vitamin D deficiency is related to head and neck cancer (HNC) etiology and outcome. RECENT FINDINGS: The search yielded five prospective studies reporting 25(OH)D levels prior to cancer diagnosis and their effect on the risk of HNC. Eight studies were cross-sectional or case-control studies, in which 25(OH)D levels were only measured after cancer diagnosis. Two studies found an inverse association between 25(OH)D level and HNC risk, while two other prospective cohort studies demonstrated no connection between 25(OH)D and HNC risk. Several studies reported cancer patients to have significantly lower 25(OH)D levels than controls. Associations between 25(OH)D and prognosis and mortality were variable. The link between vitamin D and HNC has so far only been investigated in a few observational, prospective, and case-control studies. Vitamin D deficiency may be more common in HNC patients than in the healthy population. There is no evidence for a causal relationship. Further studies are needed to evaluate whether low 25(OH)D concentrations play a role in the development or outcome of HNCs.

Management of the Neck in Well-Differentiated Thyroid Cancer.

PURPOSE OF REVIEW: In this narrative review, we discuss the indications for elective and therapeutic neck dissections and the postoperative surveillance and treatment options for recurrent nodal disease in patients with well-differentiated thyroid cancer. RECENT FINDINGS: Increased availability of advanced imaging modalities has led to an increased detection rate of previously occult nodal disease in thyroid cancer. Nodal metastases are more common in young patients, large primary tumors, specific genotypes, and certain histological types. While clinically evident nodal disease in the lateral neck compartments has a significant oncological impact, particularly in the older age group, microscopic metastases to the central or the lateral neck in well-differentiated thyroid cancer do not significantly affect outcome. As patients with clinically evident nodal disease are associated with worse outcomes, they should be treated surgically in order to reduce rates of regional recurrence and improve survival. The benefit of elective neck dissection remains unverified as the impact of microscopic disease on outcomes is not significant.