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.

Impact of lymph node ratio and number of lymph node metastases on survival and recurrence in laryngeal squamous cell carcinoma.

INTRODUCTION: The aim of this study is to assess the impact of lymph node ratio (LNR) and number of positive lymph nodes (NPLN) on mortality and recurrence rates in patients with laryngeal squamous cell carcinoma. MATERIALS AND METHODS: We conducted a retrospective multicenter international study involving 24 Otorhinolaryngology-Head and Neck Surgery divisions. Disease-specific survival (DSS) and disease-free survival (DFS) were evaluated as the main outcomes. The curves for DSS and DFS according to NPLN and LNR were analyzed to identify significant variations and establish specific cut-off values. RESULTS: 2507 patients met the inclusion criteria. DSS and DFS were significantly different in the groups of patients stratified according to LNR and NPLN. The 5-year DSS and DFS based on LNR and NPLN demonstrated an improved ability to stratify patients when compared to pN staging. CONCLUSION: Our data demonstrate the potential prognostic value of NPLN and LNR in laryngeal squamous cell carcinoma.

Recipient vessels for free flaps in advanced facial oncologic defects.

OBJECTIVES: To prospectively compare the results of microvascular flap reconstruction of midface and scalp advanced oncologic defects using superficial temporal versus cervical as recipient vessels. METHODS: This is a parallel group clinical trial with 1:1 allocation ratio of patients who underwent midface and scalp oncologic reconstruction with free tissue flap from April 2018 to April 2022 in a tertiary oncologic center. Two groups were analyzed: those in whom superficial temporal vessels were used as the recipient vessels (Group A) and those in whom cervical vessels were used as the recipient vessels (Group B). Patient gender and age, cause and localization of the defect, flap choice for reconstruction, recipient vessels, intraoperative outcome, postoperative course, and complications were recorded and analyzed. A Fisher's exact test was used to compare outcomes between the 2 groups. RESULTS: On the basis of the different recipient vessels, 32 patients were randomized into 2 groups, and of these 27 patients completed the study: Group A with superficial temporal recipient vessels (n = 12) and Group B with cervical recipient vessels (n = 15). There were 18 male and 09 female patients with an average age of 53.92 ±â€¯17.49 years. The overall flap survival rate was 88.89%. The overall complication rate for vascular anastomosis was 14.81%. The total flap loss rate in patients with superficial temporal recipient vessels was higher than the complication rate in those with cervical recipient vessels but with no statistical significance (16.67% vs. 6.66%, p = 0.569). Minor complications occurred in 05 patients without statistical significance between the groups (p = 0.342). CONCLUSION: In the group with superficial temporal recipient vessels, the postoperative rate of free flap complications was similar than the cervical recipient vessel group. Therefore the use of superficial temporal recipient vessels for midface and scalp oncologic reconstruction could be a reliable option.

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.

Recipient vessels for free flaps in advanced facial oncologic defects

Abstract Objectives To prospectively compare the results of microvascular flap reconstruction of midface and scalp advanced oncologic defects using superficial temporal versus cervical as recipient vessels. Methods This is a parallel group clinical trial with 1:1 allocation ratio of patients who underwent midface and scalp oncologic reconstruction with free tissue flap from April 2018 to April 2022 in a tertiary oncologic center. Two groups were analyzed: those in whom superficial temporal vessels were used as the recipient vessels (Group A) and those in whom cervical vessels were used as the recipient vessels (Group B). Patient gender and age, cause and localization of the defect, flap choice for reconstruction, recipient vessels, intraoperative outcome, postoperative course, and complications were recorded and analyzed. A Fisher's exact test was used to compare outcomes between the 2 groups. Results On the basis of the different recipient vessels, 32 patients were randomized into 2 groups, and of these 27 patients completed the study: Group A with superficial temporal recipient vessels (n = 12) and Group B with cervical recipient vessels (n = 15). There were 18 male and 09 female patients with an average age of 53.92 ± 17.49 years. The overall flap survival rate was 88.89%. The overall complication rate for vascular anastomosis was 14.81%. The total flap loss rate in patients with superficial temporal recipient vessels was higher than the complication rate in those with cervical recipient vessels but with no statistical significance (16.67% vs. 6.66%, p= 0.569). Minor complications occurred in 05 patients without statistical significance between the groups (p= 0.342). Conclusion In the group with superficial temporal recipient vessels, the postoperative rate of free flap complications was similar than the cervical recipient vessel group. Therefore the use of superficial temporal recipient vessels for midface and scalp oncologic reconstruction could be a reliable option.

The impact of sentinel lymph node biopsy on the quality of life in patients with oral cavity squamous cell carcinoma / Impacto da biópsia do linfonodo sentinela na qualidade de vida em pacientes com carcinoma espinocelular da cavidade oral

Abstract Introduction Sentinel lymph node biopsy is a proven method for staging the neck in patients with early oral cavity squamous cell carcinoma because it results in less comorbidity than the traditional method of selective neck dissection, with the same oncological results. However, the real effect of that method on the quality of life of such patients remains unknown. Objective The present study aimed to evaluate the quality of life of patients with oral cavity squamous cell carcinoma T1/T2N0 submitted to sentinel lymph node biopsy compared to those that received selective neck dissection. Methods Cross-sectional study including 24 patients, after a 36 month follow-up, 15 of them submitted to the sentinel lymph node biopsy and 9 to selective neck dissection. All patients answered the University of Washington quality of life questionnaire. Results The evaluation of the questionnaires showed a late worsening of the domains appearance (p = 0.035) and chewing (p = 0.041), as well as a decrease of about 10% of general quality of life (p = 0.025) in patients undergoing selective neck dissection ​​in comparison to those undergoing sentinel lymph node biopsy. Conclusion Patients with early-stage oral cavity squamous cell carcinoma undergoing sentinel lymph node biopsy presented better late results of general quality of life, mainly regarding appearance and chewing, when compared to patients submitted to selective neck dissection.

Resumo Introdução A biópsia de linfonodo sentinela é um método comprovado para estadiamento cervical em pacientes com carcinoma espinocelular inicial da cavidade oral, porque apresenta menor taxa de morbidade do que o método tradicional de esvaziamento cervical seletivo, com os mesmos resultados oncológicos. Porém, o verdadeiro efeito desse método na qualidade de vida desses pacientes permanece desconhecido. Objetivo Avaliar a qualidade de vida de pacientes com carcinoma espinocelular de cavidade oral T1/T2N0 submetidos a biópsia do linfonodo sentinela em comparação aos pacientes nos quais o esvaziamento cervical seletivo foi feito. Método Estudo transversal que incluiu 24 pacientes, após 36 meses de seguimento, dos quais 15 foram submetidos a biópsia do linfonodo sentinela e nove a esvaziamento cervical seletivo. Todos os pacientes responderam ao questionário de qualidade de vida da University of Washington. Resultados A avaliação dos questionários evidenciou pioria tardia dos domínios aparência (p = 0,035) e mastigação (p = 0,041), bem como diminuição de cerca de 10% da qualidade de vida geral (p = 0,025) nos pacientes submetidos a esvaziamento cervical seletivo em comparação com aqueles submetidos a biópsia do linfonodo sentinela. Conclusão Pacientes com carcinoma espinocelular de cavidade oral em estágio inicial submetidos a biópsia do linfonodo sentinela apresentaram melhores resultados tardios de qualidade de vida geral, principalmente quanto à aparência e à mastigação, quando comparados aos pacientes submetidos a esvaziamento cervical seletivo.

Epithelial-mesenchymal transition related to bone invasion in oral squamous cell carcinoma.

INTRODUCTION: Bone invasion is an important prognostic factor in oral squamous cell carcinoma, leading to a lower survival rate and the use of aggressive treatment approaches. Epithelial-mesenchymal transition (EMT) is possibly involved in this process, because it is often related to mechanisms of cell motility and invasiveness. This study examined whether a panel of epithelial-mesenchymal markers are present in cases of oral squamous cell carcinoma with bone invasion and whether these proteins have any relationship with patients' clinical-pathological parameters and prognostic factors. METHODS: Immunohistochemical analysis of E-cadherin, twist, vimentin, TGFß1, and periostin was performed in paraffin-embedded samples of 62 oral squamous cell carcinoma cases. RESULTS: The analysis revealed that most cases (66%) presented with a dominant tumor infiltrative pattern in bone tissue, associated with lower survival rates, when compared with cases with a dominant erosive invasion pattern (P = 0.048). Twenty-seven cases (43%) expressed markers that were compatible with total or partial EMT at the tumor-bone interface. There was no association between evidence of total or partial EMT and other demographic or prognostic features. E-cadherin-positive cases were associated with tobacco smoking (P = 0.022); vimentin-positive cases correlated with tumors under 4 cm (P = 0.043). Twistexpression was observed in tumors with a dominant infiltrative pattern (P = 0.041) and was associated with the absence of periostin (P = 0.031). CONCLUSION: We observed evidence of total or partial EMT in oral squamous cell carcinoma bone invasion. The transcription factor twist appears to be involved in bone invasion and disease progression.

Comprehensive management of nonmelanoma skin cancer involving the skull base.

PURPOSE OF REVIEW: Skin cancers are the most prevalent malignant disorder affecting humans. Approximately 90% of these are nonmelanoma skin cancer (NMSC), and large tumors, especially at the 'H-zone', can invade deeply and access the skull base. The best treatment for these very advanced skin cancers is craniofacial resection followed by adjuvant treatment, but, currently, systemic therapy and neoadjuvant approaches could be considered for some patients. The current management of NMSC involving the skull base is discussed in this article. RECENT FINDINGS: Surgical resections with negative margins followed by adjuvant treatment are the best treatment for NMSC with skull base invasion and offer the best outcomes for those patients. This approach usually requires a free flap reconstruction, followed by external beam radiation therapy. The team must keep in mind that some factors, such as gross brain invasion and extensive dura mater extension, are associated with worse outcomes. SUMMARY: Although it occurs infrequently, very advanced NMSC can involve the skull base. In these very difficult clinical scenarios, the best therapeutic option is a multidisciplinary approach in a tertiary center.

The impact of sentinel lymph node biopsy on the quality of life in patients with oral cavity squamous cell carcinoma.

INTRODUCTION: Sentinel lymph node biopsy is a proven method for staging the neck in patients with early oral cavity squamous cell carcinoma because it results in less comorbidity than the traditional method of selective neck dissection, with the same oncological results. However, the real effect of that method on the quality of life of such patients remains unknown. OBJECTIVE: The present study aimed to evaluate the quality of life of patients with oral cavity squamous cell carcinoma T1/T2N0 submitted to sentinel lymph node biopsy compared to those that received selective neck dissection. METHODS: Cross-sectional study including 24 patients, after a 36 month follow-up, 15 of them submitted to the sentinel lymph node biopsy and 9 to selective neck dissection. All patients answered the University of Washington quality of life questionnaire. RESULTS: The evaluation of the questionnaires showed a late worsening of the domains appearance (p=0.035) and chewing (p=0.041), as well as a decrease of about 10% of general quality of life (p=0.025) in patients undergoing selective neck dissection ​​in comparison to those undergoing sentinel lymph node biopsy. CONCLUSION: Patients with early-stage oral cavity squamous cell carcinoma undergoing sentinel lymph node biopsy presented better late results of general quality of life, mainly regarding appearance and chewing, when compared to patients submitted to selective neck dissection.

Survival in differentiated thyroid carcinoma: Comparison between the 7th and 8th editions of the AJCC/UICC TNM staging system and the ATA initial risk stratification system.

BACKGROUND: The AJCC/UICC TNM staging system evaluates the risk of death from cancer. Its 8th edition aimed to increase its accuracy. In turn, the American Thyroid Association proposed an initial risk stratification system (IRSS) focusing on the risk of recurrence in differentiated thyroid carcinoma. The present study intended to analyze their prediction abilities. METHODS: Six hundred and eighty-five consecutive surgical patients (mean follow-up 71.6 months) were staged. Correlations with disease-free survival (DFS) and overall survival (OS) were carried out. RESULTS: IRSS was discriminative for DFS but not for OS. Applying TNM 8th, 36.9% of the cohort was downstaged. Their DFS was shorter, compared with other patients in the same stage, but with no impact on OS. However, all those who died of the disease had been downstaged. CONCLUSIONS: IRSS was more effective to predict DFS, but not OS. TNM 8th was more appropriate for OS analysis than TNM 7th and IRSS.

Oral Squamous Cell Carcinoma Bone Invasion: Possible Roles of E-Cadherin in Osteoclastogenesis and Bone Infiltration.

INTRODUCTION: Squamous cell carcinoma is the most common cancer of the oral cavity. When the tumor invades the bone tissue, the prognostic and survival rates decrease a lot, and the treatment becomes more aggressive, with several damages to the patient and health system. Many of the molecular mechanisms of bone invasion process are not understood yet, but it is already known that one of central processes of tumor evolution - adjacent tissues invasion and metastasis - is a large spectrum of phenotypic changes in epithelial cells to mesenchymal, in a process named as epithelial-mesenchymal transition (EMT). Loss of E-cadherin, an important epithelial cell adhesion protein, is a hallmark of this phenomenon. The objective of this retrospective study is to evaluate the expression of E-cadherin protein, comparing its distribution with clinical characteristics of the patients and possibly relation to EMT. METHODS: Sixty-two cases with respective clinical data were analyzed by comparing immunohistochemical, H and E staining, and clinical data, observing the tumor-bone interface (TBI) and the surrounding tumor that had no direct contact with the bone surface (ST). RESULTS: Forty cases were positive for E-cadherin (64%) with a heterogeneous pattern. Statistical analysis showed a significant difference between the presence of E-cadherin expression and tobacco smokers. Also, the equal or weaker protein expression in the ST than TBI is related to a worse overall survival. No statistically significant difference in other prognostic factors was observed. CONCLUSION: Our results suggest that the tumor cells that interact with the bone tissue could gain molecular changes, like partial EMT and osteoclastogenesis induction, which facilitate their migration and increase the bone resorption, resulting in a worse patient's prognosis.

Fascicular Turnover Flap: An Approach for Facial Nerve Reconstruction.

ABSTRACT: Facial nerve injuries are a common complication associated with parotidectomy. These functionally debilitating injuries are conventionally treated with nonvascularized nerve grafting; however, this reconstructive modality produces moderate donor site morbidity and has limited efficacy for repairing large defects. In addition, nonvascularized nerve grafts are highly susceptible to radiotherapy and require a well-vascularized wound bed to produce adequate therapeutic results. The fascicular turnover flap, described by Koshima et al, utilizes a single fascicle to bridge two nerve endings that are in series with no donor site morbidity. Although studies have demonstrated this technique's efficacy, there is a paucity of data regarding its use in patients undergoing facial nerve reconstruction. Herein, we describe our early clinical experience using the fascicular turnover flap to reconstruct branches of the facial nerve in patients undergoing extensive parotidectomy. Our patients underwent successful reconstruction of the nerve defects produced by parotidectomy using the fascicular turnover flap. Despite postoperative radiotherapy, both patients demonstrated complete functional recovery at six months postoperatively. Although formal head-to-head studies are needed to compare the outcomes of this technique versus conventional nerve grafting for facial nerve reconstruction, our preliminary experiences suggest that the fascicular turnover flap is a viable modality of reconstruction with great potential.

MicroRNA-mediated extracellular matrix remodeling in squamous cell carcinoma of the oral cavity.

BACKGROUND: We evaluated microRNAs and extracellular matrix component profiles in squamous cell carcinoma of the oral cavity (OSCC) in comparison to healthy mucosa. METHODS: Retrospective study investigating 64 microRNAs related to oncogenic process and to constituents of the extracellular matrix. We also performed immunohistochemical assays for molecules involved in the same biological processes. RESULTS: High expression of miR-21-5p (p < 0.001) and miR-106-5p (p < 0.001) and low expression of miR-320a (p = 0.001) and miR-222-3p (p = 0.001) were predictors of malignancy. Individually, miR-21-5p exhibited the best statistical performance (area under the curve = 0.972; 95% confidence interval: 0.911-1.000) in the differentiation between tumor tissue and healthy mucosa. Moreover, tumor sample showed increased expression of MMP-2, MMP-9, α-laminin, and ß-laminin in tumor-related fibroblasts and lower continuity of type IV collagen in the basement membrane. CONCLUSION: The present study demonstrates the biological effects of microRNAs on the carcinogenesis of OSCC as well as the intense modification of the tumor microenvironment.

Thyroid cancer surgical indication during pregnancy: systematic literature review and series of illustrative cases

Introduction: Thyroid papillary carcinoma is the second most frequent type of cancer during pregnancy. Its diagnosis is related to patient fear and anxiety. There is little consensus on when to perform surgery in those cases. Objective: To evaluate and discuss timing possibilities for surgical treatment in thyroid cancer in pregnant women. Methods: Systematic literature review based on online search at the Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS) and National Center for Biotechnology Information (NCBI) databases. Retrospective analysis of thyroidectomies performed in the second trimester of pregnancy by the authors between 1999 and 2019. Results: The systematic review included nine articles. Their conclusions diverge with respect to the optimal timing of thyroid surgery. The medical literature considers thyroidectomy after safe delivery. The most recent studies are more flexible regarding carrying out this surgery during the second trimester of pregnancy. In the authors' experience (n=5), surgical treatment during the second trimester of pregnancy is a good option for more aggressive tumors. Conclusion: More aggressive cases of thyroid papillary carcinoma can be treated with surgery during the second trimester of pregnancy. Performing the surgery after delivery is safer in the case of less aggressive cancer cases. The decision should consider hospital costs, surgery risks, and patient anxiety in relation to cancer.

Prelaminated Supraclavicular Island Flap for Total Ear Reconstruction: A New Technique.

Major ear reconstruction has progressed over the past years with the emergence of new techniques directed mainly to patients without available or usable local skin. However, microsurgical transfer requires specific training and eligible patients. The authors report a successful ear reconstruction with a prelaminated supraclavicular island flap in 3 stages, which may be a valuable resource for selected patients or when microsurgery is not available. Advantages and disadvantages of this new technique are discussed, and a possible solution to achieve a more satisfactory result is suggested.

Cancer-associated fibroblast regulation by microRNAs promotes invasion of oral squamous cell carcinoma.

The objective of the present study was to evaluate the role of microRNA-mediated remodeling of the extracellular matrix in the process of tumor invasion of oral squamous cell carcinoma and to evaluate its relationship with the prognosis of these patients. This was a retrospective study on material from the paraffin blocks of patients operated on for oral squamous cell carcinoma, in addition to a group of healthy oral mucosa samples of paired patients. miR-1-3p, miR-133-3p, and miR-21-5p were differentially expressed between the superficial and deep tumor groups. miR-21-5p was the one with the greatest accuracy in the differentiation between superficial and deep tumors. By immunohistochemistry, the group of deep tumors showed greater immunoreactivity to matrix metalloproteinases 2 and 9 and laminin α in tumor-associated fibroblasts, with consequent degradation of the basal membrane, measured by greater loss of continuity of type IV collagen. This process was also associated with lower and higher expression of miR-1-3p and miR-21-5p, respectively. There was also a trend toward better overall and disease-free survival rates in patients with higher miR-133a-3p. The present study showed the interaction between microRNAs and extracellular matrix remodeling in oral squamous cell carcinoma.

Superficial cervical plexus blockade improves pain control after thyroidectomy: A randomized controlled trial.

OJECTIVES: The aim was to evaluate the ability of bilateral superficial cervical plexus blockade to control pain and to reduce the side effects of general anesthesia in patients submitted to thyroidectomy. METHODS: In this randomized controlled trial, we prospectively studied 100 consecutive patients who underwent total thyroidectomy. The simple random patient sample was divided into two groups: 50 patients received general anesthesia alone (group 1 [G1]), and 50 patients received general anesthesia with bilateral superficial cervical plexus blockade (group 2 [G2]). Statistical analyses were performed, and a 5% significance level was adopted. RESULTS: The mean arterial blood pressure and heart rate were 12% lower in G2 patients than in G1 patients 60 minutes after surgery (101 mmHg for G1 vs. 92.3 mmHg for G2; p<0.001). G2 patients reported less pain than G1 patients, and opioid consumption was lower in G2 patients than in G1 patients, not upon postanesthesia care unit arrival, but at 30 minutes (2% vs. 34%; p<0.001, respectively), 45 minutes (0% vs. 16%; p=0.006, respectively), and 4 hours postoperatively (6% vs. 20%; p=0.037, respectively). The incidence of nausea and vomiting was lower in G2 patients than in G1 patients from 45 minutes (0% vs. 16%; p=0.006, respectively) to 8 hours postoperatively (0% vs. 14%; p=0.012, respectively). CONCLUSIONS: The present study demonstrated that the combination of bilateral superficial cervical plexus blockade with general anesthesia for thyroidectomy is feasible, safe, and effective for achieving pain control and improving patient outcomes.