Association of the Specimen and Tumor Bed Margin Status with Local Recurrence and Survival in Open Partial Laryngectomy.

Background/Objectives: Positive margins are associated with locoregional recurrence in early laryngeal cancer. The aim of this study was to evaluate the impacts of specimen-driven (ex vivo) positive margins on patients with early-stage laryngeal cancer whose tumor bed (defect-driven) margins had been negative. Methods: A retrospective study was performed on 60 consecutive T1b/T2 glottic cancer patients who underwent open frontolateral laryngectomy. The intraoperative margins were obtained from the tumor bed. Their recurrence and disease-free survival were evaluated. In all cases, negative margins were obtained from the surgical bed. The impact of positive margins from the specimen was evaluated in a paraffin study. Results: Among 10 patients with positive margins in the specimen, six experienced local relapse, and among 50 patients with negative margins in the specimen, three developed recurrence. The 5-year disease-free survival rates were 37.5% and 93.9%, respectively (p < 0.001; log-rank). Even with negative margins in the surgical bed, patients with positive margins in the specimen at the final histopathological examination had a 3.5-fold higher chance of developing local recurrence than those with negative margins (HR = 13.993; 95% CI: 3.479-56.281; p < 0.001; univariate Cox regression). Conclusions: Specimen-driven positive margins represent a significant risk factor for local recurrence, even under negative margins at the tumor bed.

Latin American Consensus on the Treatment of Head and Neck Cancer.

Head and neck squamous cell carcinoma (HNSCC) is well known as a serious health problem worldwide, especially in low-income countries or those with limited resources, such as most countries in Latin America. International guidelines cannot always be applied to a population from a large region with specific conditions. This study established a Latin American guideline for care of patients with head and neck cancer and presented evidence of HNSCC management considering availability and oncologic benefit. A panel composed of 41 head and neck cancer experts systematically worked according to a modified Delphi process on (1) document compilation of evidence-based answers to different questions contextualized by resource availability and oncologic benefit regarding Latin America (region of limited resources and/or without access to all necessary health care system infrastructure), (2) revision of the answers and the classification of levels of evidence and degrees of recommendations of all recommendations, (3) validation of the consensus through two rounds of online surveys, and (4) manuscript composition. The consensus consists of 12 sections: Head and neck cancer staging, Histopathologic evaluation of head and neck cancer, Head and neck surgery-oral cavity, Clinical oncology-oral cavity, Head and neck surgery-oropharynx, Clinical oncology-oropharynx, Head and neck surgery-larynx, Head and neck surgery-larynx/hypopharynx, Clinical oncology-larynx/hypopharynx, Clinical oncology-recurrent and metastatic head and neck cancer, Head and neck surgery-reconstruction and rehabilitation, and Radiation therapy. The present consensus established 48 recommendations on HNSCC patient care considering the availability of resources and focusing on oncologic benefit. These recommendations could also be used to formulate strategies in other regions like Latin America countries.

Total laryngectomy vs. non-surgical organ preservation in advanced laryngeal cancer: a metanalysis.

OBJECTIVE: To compare the oncological results and the functional outcomes of patients undergoing Total Laryngectomy (TL) with the non-surgical treatment (organ preservation protocol) in the treatment of advanced laryngeal carcinomas through systematic review and meta-analysis. METHODS: A literature survey strategy was employed in order to perform a systematic review of the available evidence. Success rate and functional outomes after oncological treatment of patients with advanced laryngeal carcinomas was evaluated through systematic review and metanalysis, comparing TL and organ preservation protocol. RESULTS: The surgical treatment was associated with better survival outcomes. When stratifying by T stage, while patients with T4 staging have less risk of mortality with TL, there is no difference between the different treatments for patients with T3 tumors. Surgery is related to a lower chance of recurrence, late dysphagia and feeding tube dependence. CONCLUSION: Patients with T4 tumors should undergo TL as their treatment of choice. For patients with T3 tumors, there is no differences on the risk of mortality according to the therapeutic option, however, there is a greater chance of recurrence and dysphagia when surgery is not performed.

Detection of serum biomarkers of HPV-16 driven oropharynx and oral cavity cancer in Brazil.

BACKGROUND: HPV-16 driven oropharynx/oral cavity squamous cell carcinomas prevalence varies globally. We evaluated the presence of HPV-16 ctDNA and HPV-16 E6 antibodies in samples obtained from participants treated at the Instituto do Cancer do Estado de Sao Paulo, ICESP, and from whom tumoral HPV DNA, HPV-16 E6*I mRNA, and p16INK4a status was also accessed. METHODS: HPV was genotyped by PCR-hybridization. All HPV DNA positive and ∼10 % HPV DNA negative cases underwent p16INK4a immunohistochemistry and E6*I RNA testing using a multiplex bead based protocol. HPV-16 ctDNA and anti-E6 antibodies were assessed by ddPCR (digital droplet PCR) and multiplex serology, respectively. RESULTS: The prevalence of HPV-16 in oropharynx carcinoma (OPC) cases was low (8.7 %) when considering solely HPV-16 DNA detection, and even lower (5.2 %) when taken into consideration the concomitant detection of HPV-16 E6*I RNA and/or p16INK4 (HPV-16 attributable fraction - AF). None of the oral cavity cancer (OCC) cases were detected with HPV-16 DNA. HPV-16 ctDNA was more commonly detected than HPV-16 E6 antibodies (29.8 % versus 10.6 %). Both serum biomarkers attained 100 % sensitivity of detecting HPV-16 AF OPC, however the specificity of the HPV-16 anti-E6 biomarker was higher compared to ctDNA (93.2 % versus 75.0 %). Finally, when both HPV-16 ctDNA and anti-E6 biomarkers were considered together, the sensitivity and specificity for HPV-16 OPC detection was 100 % and about 70 %, respectively, independently of analyzing HPV-16 DNA positive or HPV-16 AF tumors. CONCLUSIONS: Our findings corroborate that serum biomarkers are highly sensitive and specific biomarkers for detection of HPV-associated OPC.

Medical students' and residents' views on euthanasia.

BACKGROUND: Doctors are increasingly faced with end-of-life decisions. Little is known about how medical students approach euthanasia. The objective of this study was to evaluate, among medical students and residents, the view on euthanasia and its variants; correlate such a view with empathy and religiosity/spiritualism; and with the stages of medical training in Brazil. METHODS: This is an exploratory cross-sectional study using an online questionnaire to be filled out on a voluntary basis among medical students and residents, consisting of: socio-demographic data, an empathy questionnaire and questions with elaborate clinical cases that typify situations of the variants of euthanasia. RESULTS: From 1550 invitations, 273 volunteer participants responded (17.6%). The percentages of strong agreement/agreement on the concepts were: passive euthanasia (72.9%); active euthanasia (22.3%), orthothanasia (90.1%), dysthanasia (18.7%), assisted suicide (33%) and sedation (82.8%). Passive euthanasia, active euthanasia, dysthanasia and assisted suicide showed greater refusal with increasing length of medical training. Religious belief and degree of empathy did not significantly influence the opinion about the concepts. Strong agreement/agreement were: passive euthanasia (72.9%); active euthanasia (22.3%), orthothanasia (90.1%), dysthanasia (18.7%), assisted suicide (33%) and sedation (82.8%). CONCLUSIONS: Passive euthanasia, active euthanasia, dysthanasia and assisted suicide showed greater refusal with increasing length of medical training. The external validation of our findings relies on the distinct legal, cultural, and religious frameworks found across various countries.

Prognostic Value of Hematological Parameters in Oral Squamous Cell Carcinoma.

INTRODUCTION: Oral squamous cell carcinoma (OSCC) remains a significant public health concern. The variables utilized to determine appropriate treatment for this disease also represent its most unfavorable prognostic factors, with these parameters solely determined by the neoplasm and its behavior. However, a lack of well-established indices is evident in the literature that specifically relate to the patient and indicate a worse prognosis. OBJECTIVE: To assess the prognostic impact of hematological indices in patients with OSCC. METHODS: This retrospective cohort study included patients with oral squamous cell carcinoma (OSCC) who underwent curative-intent treatment. Treatment encompassed surgery, followed by adjuvant therapy, as necessary. Laboratory tests were conducted immediately prior to surgery, and demographic information was obtained from medical records. RESULTS: The cohort comprised 600 patients, with 73.5% being male subjects. Adjuvant treatment was recommended for 60.3% of patients. Throughout the follow-up period, 48.8% of participants died. Univariate analysis indicated that perineural invasion, angiolymphatic invasion, pT4 tumors, lymph node metastases, extranodal extravasation, RDW > 14.3%, NLR (neutrophil-lymphocyte ratio) > 3.38, PLR (platelet-lymphocyte ratio) > 167.3, and SII (systemic inflammatory/immune response index) > 416.1 were factors associated with increased mortality. These threshold values were established through ROC curve analysis. In the multivariate analysis, angiolymphatic invasion (HR = 1.43; 95% CI: 1.076-1.925; p = 0.014), pT4a/b tumors (HR = 1.761; 95% CI: 1.327-2.337; p < 0.001), extranodal extravasation (HR = 1.420; 95% CI: 1.047-1.926; p = 0.024), and RDW (HR = 1.541; 95% CI: 1.153-2.056; p = 0.003) were identified as independent risk factors for decreased overall survival. CONCLUSIONS: RDW > 14.3% was proven to be a reliable parameter for assessing overall survival in patients with OSCC. Further studies are required to evaluate the clinical applicability of other hematological indices.

Sialendoscopy for treatment of major salivary glands diseases: a comprehensive analysis of published systematic reviews and meta-analyses

Abstract Objectives: Sialendoscopy is a minimally invasive procedure used to diagnose and treat obstructive salivary gland diseases. Previous studies in the topic have shown mixed results. The present study aimed to evaluate the efficacy and safety of sialendoscopy through previous systematic reviews for different outcomes of several diseases. We also aimed to assess studies' methodological quality and heterogeneity. Methods: We conducted a comprehensive systematic literature search of Pubmed, Embase, Lilacs and Cochrane Library. We included systematic reviews and meta-analyses that used sialendoscopy to treat both lithiasic and alithiasic salivary glands diseases. Data extraction included studies' characteristics and results. We assessed studies' methodological quality using the AMSTAR-2 (A Measurement Tool to Assess systematic Reviews 2) tool. Results: 13 studies were included in the review, being 9 in adult populations and 4 in pediatric populations. Sialendoscopy proved to be effective at the treatment of different lithiasic and other obstructive diseases, but with important heterogeneity. The technique was also considered highly safe in most studies. However, studies had a critically low quality of evidence. Conclusions: Most studies demonstrated high efficacy and safety of sialendoscopy, but with critically low quality of evidence. We still lack randomized studies in this field, and future systematic reviews on the topic should follow current guidelines to improve conduction and reporting.

Sialendoscopy for treatment of major salivary glands diseases: a comprehensive analysis of published systematic reviews and meta-analyses.

OBJECTIVES: Sialendoscopy is a minimally invasive procedure used to diagnose and treat obstructive salivary gland diseases. Previous studies in the topic have shown mixed results. The present study aimed to evaluate the efficacy and safety of sialendoscopy through previous systematic reviews for different outcomes of several diseases. We also aimed to assess studies' methodological quality and heterogeneity. METHODS: We conducted a comprehensive systematic literature search of Pubmed, Embase, Lilacs and Cochrane Library. We included systematic reviews and meta-analyses that used sialendoscopy to treat both lithiasic and alithiasic salivary glands diseases. Data extraction included studies' characteristics and results. We assessed studies' methodological quality using the AMSTAR-2 (A MeaSurement Tool to Assess systematic Reviews 2) tool. RESULTS: 13 studies were included in the review, being 9 in adult populations and 4 in pediatric populations. Sialendoscopy proved to be effective at the treatment of different lithiasic and other obstructive diseases, but with important heterogeneity. The technique was also considered highly safe in most studies. However, studies had a critically low quality of evidence. CONCLUSIONS: Most studies demonstrated high efficacy and safety of sialendoscopy, but with critically low quality of evidence. We still lack randomized studies in this field, and future systematic reviews on the topic should follow current guidelines to improve conduction and reporting.

Congenital Midline Cervical Cleft and Thyroglossal Duct Fibrous Cord-Like, is There a Mixed Presentation?

INTRODUCTION: Congenital midline cervical cleft is a rare condition and is frequently misdiagnosed as thyroglossal duct cyst. Otherwise, the combination of congenital midline cervical cleft and thyroglossal duct fibrosis in the same patient is as rare as important to be registered with the intention to inform and offer specific managements details for the literature. CASE PRESENTATION: Eight-year-old boy with simultaneous congenital midline cervical cleft and a thyroglossal duct fibrosis. The anatomic, clinical, radiologic, and pathologic characteristics of the congenital midline cervical cleft are described as well as surgical technique for removal and repair with Z-plasty. CONCLUSION: Congenital midline cervical cleft is a rare condition and when diagnosed must be surgically treated as early as possible. Its differential diagnosis is a clinical challenge.

Comprehensive Glycoprofiling of Oral Tumors Associates N-Glycosylation With Lymph Node Metastasis and Patient Survival.

While altered protein glycosylation is regarded a trait of oral squamous cell carcinoma (OSCC), the heterogeneous and dynamic glycoproteome of tumor tissues from OSCC patients remain unmapped. To this end, we here employ an integrated multi-omics approach comprising unbiased and quantitative glycomics and glycoproteomics applied to a cohort of resected primary tumor tissues from OSCC patients with (n = 19) and without (n = 12) lymph node metastasis. While all tumor tissues displayed relatively uniform N-glycome profiles suggesting overall stable global N-glycosylation during disease progression, altered expression of six sialylated N-glycans was found to correlate with lymph node metastasis. Notably, glycoproteomics and advanced statistical analyses uncovered altered site-specific N-glycosylation revealing previously unknown associations with several clinicopathological features. Importantly, the glycomics and glycoproteomics data unveiled that comparatively high abundance of two core-fucosylated and sialylated N-glycans (Glycan 40a and Glycan 46a) and one N-glycopeptide from fibronectin were associated with low patient survival, while a relatively low abundance of N-glycopeptides from both afamin and CD59 were also associated with poor survival. This study provides insight into the complex OSCC tissue N-glycoproteome, thereby forming an important resource to further explore the underpinning disease mechanisms and uncover new prognostic glycomarkers for OSCC.

Impact of the COVID-19 Pandemic on Brazilian Head and Neck Surgery Centers

Abstract Objective The outbreak of the COVID-19 pandemic had a considerable impact on the healthcare access, treatment, and follow-up of oncologic patients. The aim of this study was to evaluate how the COVID-19 pandemic has affected consultation and follow-up demand as well as treatment volume at Brazilian Head and Neck Surgery centers. Methods An anonymous online questionnaire was used for collection of data across all Brazilian Head and Neck Surgery Centers across a 3-month period (April‒June 2021). This information included the characteristics of each center, and the perceived self-reported impact of the COVID-19 pandemic on academic activities, residency training, and the diagnosis, treatment, and follow-up of patients with Head and Neck diseases between 2019 and 2020. Results The response rate across the 40 registered Brazilian Head and Neck Surgery Centers was 47.5% (n = 19). The data showed a significant reduction in the total number of consultations (24.8%) and number of attending patients (20.2%) between 2019 and 2020. The total number of diagnostic exams (31.6%) and surgical procedures (13.0%) conducted over this period also decreased significantly. Conclusions The COVID-19 pandemic had a significant national impact on Brazilian Head and Neck Surgery Centers. Future studies should examine the long-term effects of the pandemic on cancer treatment. Level of evidence Evidence from a single descriptive study.

Effect of the COVID-19 pandemic on surgery for indeterminate thyroid nodules (THYCOVID): a retrospective, international, multicentre, cross-sectional study.

BACKGROUND: Since its outbreak in early 2020, the COVID-19 pandemic has diverted resources from non-urgent and elective procedures, leading to diagnosis and treatment delays, with an increased number of neoplasms at advanced stages worldwide. The aims of this study were to quantify the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic; and to evaluate whether delays in surgery led to an increased occurrence of aggressive tumours. METHODS: In this retrospective, international, cross-sectional study, centres were invited to participate in June 22, 2022; each centre joining the study was asked to provide data from medical records on all surgical thyroidectomies consecutively performed from Jan 1, 2019, to Dec 31, 2021. Patients with indeterminate thyroid nodules were divided into three groups according to when they underwent surgery: from Jan 1, 2019, to Feb 29, 2020 (global prepandemic phase), from March 1, 2020, to May 31, 2021 (pandemic escalation phase), and from June 1 to Dec 31, 2021 (pandemic decrease phase). The main outcomes were, for each phase, the number of surgeries for indeterminate thyroid nodules, and in patients with a postoperative diagnosis of thyroid cancers, the occurrence of tumours larger than 10 mm, extrathyroidal extension, lymph node metastases, vascular invasion, distant metastases, and tumours at high risk of structural disease recurrence. Univariate analysis was used to compare the probability of aggressive thyroid features between the first and third study phases. The study was registered on ClinicalTrials.gov, NCT05178186. FINDINGS: Data from 157 centres (n=49 countries) on 87 467 patients who underwent surgery for benign and malignant thyroid disease were collected, of whom 22 974 patients (18 052 [78·6%] female patients and 4922 [21·4%] male patients) received surgery for indeterminate thyroid nodules. We observed a significant reduction in surgery for indeterminate thyroid nodules during the pandemic escalation phase (median monthly surgeries per centre, 1·4 [IQR 0·6-3·4]) compared with the prepandemic phase (2·0 [0·9-3·7]; p<0·0001) and pandemic decrease phase (2·3 [1·0-5·0]; p<0·0001). Compared with the prepandemic phase, in the pandemic decrease phase we observed an increased occurrence of thyroid tumours larger than 10 mm (2554 [69·0%] of 3704 vs 1515 [71·5%] of 2119; OR 1·1 [95% CI 1·0-1·3]; p=0·042), lymph node metastases (343 [9·3%] vs 264 [12·5%]; OR 1·4 [1·2-1·7]; p=0·0001), and tumours at high risk of structural disease recurrence (203 [5·7%] of 3584 vs 155 [7·7%] of 2006; OR 1·4 [1·1-1·7]; p=0·0039). INTERPRETATION: Our study suggests that the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic period could have led to an increased occurrence of aggressive thyroid tumours. However, other compelling hypotheses, including increased selection of patients with aggressive malignancies during this period, should be considered. We suggest that surgery for indeterminate thyroid nodules should no longer be postponed even in future instances of pandemic escalation. FUNDING: None.

Risk Factors for Malignancy in Patients with Multinodular Goiter

Abstract Introduction The identification of thyroid cancer may be conducted through clinical detection, imaging method, and histopathological examination. Both solitary nodules and multinodular goiter are associated with malignancy. Objective To assess the risk factors for malignancy among patients with multinodular goiter submitted to total thyroidectomy. Methods A series of 712 consecutive patients, submitted to total thyroidectomy between 2005 and 2016 with multinodular goiter regarding clinical, ultrasound, and pathological variables, was retrospectively evaluated. Results There were 408 cases of papillary carcinoma (57.3%), with the remaining being benign. Gender had no statistical significance (p = 0.169) for malignancy, unlike the Bethesda index, higher age group (p = 0.005), shorter clinical history time (p = 0.036), smaller number of nodules (p < 0.0001), and smaller nodule size (p < 0.0001), which were related to malignancy. Conclusion The Bethesda index, older age group, shorter clinical history, smaller number of nodules, and smaller size of nodule were related to the diagnosis of papillary carcinoma.

Profile of MicroRNAs Associated with Death Due to Disease Progression in Metastatic Papillary Thyroid Carcinoma Patients.

Papillary thyroid carcinoma (PTC) is the most common neoplasm of the endocrine system and has an excellent long-term prognosis, with low rates of distant metastatic disease. Although infrequent, there are cases of deaths directly related to PTC, especially in patients with metastatic disease, and the factors that could be associated with this unfavorable outcome remain a major challenge in clinical practice. Recently, research into genetic factors associated with PTC has gained ground, especially mutations in the TERT promoter and BRAF gene. However, the role of microRNAs remains poorly studied, especially in those patients who have an unfavorable outcome at follow-up. This paper aims to evaluate molecular markers related to the different pathological processes of PTC, as well as the histological characteristics of the neoplasm, and to compare this profile with prognosis and death from the disease using an analysis of patients treated for metastatic disease in a single tertiary cancer center. Evaluation of microRNA expression in paraffin-embedded tumor specimens was carried out by quantitative PCR using the TaqMan® Low Density Array (TLDA) system. Metastatic patients who died from progression of PTC had higher expressions of miR-101-3p, miR-17-5p, and miR-191-5p when compared to patients with stable metastatic disease. These findings are of great importance but should be considered as preliminary because of the small sample.

Incidental Node Metastasis as an Independent Factor of Worse Disease-Free Survival in Patients with Papillary Thyroid Carcinoma.

INTRODUCTION: Papillary thyroid carcinoma (PTC) have high node metastasis rates. Occasionally after thyroidectomy, the pathological report reveals node metastasis unintentionally resected. The present study aimed to evaluate the prognosis of these patients. METHODS: A retrospective cohort of patients submitted to thyroidectomy with or without central compartment neck dissection (CCND) due to PTC with a minimum follow-up of five years. RESULTS: A total of 698 patients were included: 320 Nx, 264 pN0-incidental, 37 pN1a-incidental, 32 pN0-CCND and 45 pN1a-CCND. Patients with node metastasis were younger, had larger tumors, higher rates of microscopic extra-thyroidal extension, and angiolymphatic invasion and most received radioiodine therapy. Treatment failure was higher in patients pN1a-incidental and pN1a-CCND (32% and 16%, respectively; p < 0.001-Chi-square test). Disease-free survival (DFS) was lower in patients pN1a-incidental compared to patients Nx and pN0-incidental (p < 0.001 vs. Nx and pN0-incidental and p = 0.005 vs. pN0-CCND) but similar when compared to patients pN1a-CCND (p = 0.091)-Log-Rank test. Multivariate analysis demonstrated as independent risk factors: pT4a (HR = 5.524; 95%CI: 1.380-22.113; p = 0.016), pN1a-incidental (HR = 3.691; 95%CI: 1.556-8.755; p = 0.003), microscopic extra-thyroidal extension (HR = 2.560; 95%CI: 1.303-5.030; p = 0.006) and angiolymphatic invasion (HR = 2.240; 95%CI: 1.077-4.510; p = 0.030). CONCLUSION: Patients that were pN1a-incidental were independently associated with lower DFS.

Impact of the COVID-19 Pandemic on Brazilian Head and Neck Surgery Centers.

OBJECTIVE: The outbreak of the COVID-19 pandemic had a considerable impact on the healthcare access, treatment, and follow-up of oncologic patients. The aim of this study was to evaluate how the COVID-19 pandemic has affected consultation and follow-up demand as well as treatment volume at Brazilian Head and Neck Surgery centers. METHODS: An anonymous online questionnaire was used for collection of data across all Brazilian Head and Neck Surgery Centers across a 3-month period (April‒June 2021). This information included the characteristics of each center, and the perceived self-reported impact of the COVID-19 pandemic on academic activities, residency training, and the diagnosis, treatment, and follow-up of patients with Head and Neck diseases between 2019 and 2020. RESULTS: The response rate across the 40 registered Brazilian Head and Neck Surgery Centers was 47.5% (n=19). The data showed a significant reduction in the total number of consultations (24.8%) and number of attending patients (20.2%) between 2019 and 2020. The total number of diagnostic exams (31.6%) and surgical procedures (13.0%) conducted over this period also decreased significantly. CONCLUSIONS: The COVID-19 pandemic had a significant national impact on Brazilian Head and Neck Surgery Centers. Future studies should examine the long-term effects of the pandemic on cancer treatment. LEVEL OF EVIDENCE: Evidence from a single descriptive study.

Risk Factors for Malignancy in Patients with Multinodular Goiter.

Introduction The identification of thyroid cancer may be conducted through clinical detection, imaging method, and histopathological examination. Both solitary nodules and multinodular goiter are associated with malignancy. Objective To assess the risk factors for malignancy among patients with multinodular goiter submitted to total thyroidectomy. Methods A series of 712 consecutive patients, submitted to total thyroidectomy between 2005 and 2016 with multinodular goiter regarding clinical, ultrasound, and pathological variables, was retrospectively evaluated. Results There were 408 cases of papillary carcinoma (57.3%), with the remaining being benign. Gender had no statistical significance ( p = 0.169) for malignancy, unlike the Bethesda index, higher age group ( p = 0.005), shorter clinical history time ( p = 0.036), smaller number of nodules ( p < 0.0001), and smaller nodule size ( p < 0.0001), which were related to malignancy. Conclusion The Bethesda index, older age group, shorter clinical history, smaller number of nodules, and smaller size of nodule were related to the diagnosis of papillary carcinoma.

Management of Stage III Oral Cavity Squamous Cell Carcinoma in Light of the New Staging System: a Critical Review.

PURPOSE OF REVIEW: Oral squamous cell carcinoma (OSCC) patients have a poor prognosis, especially in advanced stages. AJCC/UICC staging system 8th edition (TNM8) included depth of invasion (DOI) as part of T staging and stage III has become a heterogeneous group of lesions, composed of patients with larger DOI and/or width. Additionally, stage III includes N1, regardless of the primary tumor width or DOI. The real prognostic value of each of these characteristics and the need for adjuvant treatment for stage III patients is not well established. RECENT FINDINGS: TNM8 stratified OSCC into prognostic groups based on overall survival. Extranodal extension, positive or close margins, pT3 or pT4 tumors, pN2 or pN3 nodal disease, nodal disease in levels IV or V, perineural invasion, vascular invasion, and lymphatic invasion are the main adverse features for OSCC, and adjuvant treatment is largely recommended for these patients. Stage III patients should be addressed with caution. So far, there is no significant evidence for recommending or excluding adjuvant treatment for stage III OSCC without adverse features. The authors largely recommend adjuvant radiotherapy for these cases, especially because pT3 without adverse features is rare. Further studies on this topic are necessary.

Hydroxychloroquine for treatment of COVID-19 patients: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: We performed a systematic review of the literature and meta-analysis on the efficacy and safety of hydroxychloroquine to treat COVID-19 patients. METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and LILACS (January 2019 to March 2021) for patients aged 18 years or older, who had COVID-19 and were treated with hydroxychloroquine versus placebo or standard of care. We also searched the WHO Clinical Trials Registry for ongoing and recently completed studies, and the reference lists of selected articles and reviews for possible relevant studies, with no restrictions regarding language or publication status. Random-effects models were used to obtain pooled mean differences of treatment effect on mortality, and serious adverse effects between hydroxychloroquine and the Control Group (standard of care or placebo); heterogeneity was assessed using the I2 and the Cochran´s Q statistic. RESULTS: Nine studies met the inclusion criteria and were included in the meta-analysis. There was no significant difference in mortality rate between patients treated with hydroxychloroquine compared to standard of care or placebo (16.7% versus 18.5%; pooled risk ratio 1.09; 95% confidence interval: 0.99-1.19). Also, the rate of serious adverse effects was similar between both Groups, Hydroxychloroquine and Control (3.7% versus 2.9%; pooled risk ratio 1.22; 95% confidence interval: 0.76-1.96). CONCLUSION: Hydroxychloroquine is not efficacious in reducing mortality of COVID-19 patients. PROSPERO DATABASE REGISTRATION: (www.crd.york.ac.uk/prospero) under number CRD42020197070.