Líquen Plano Oral e seu Potencial de Malignização / Lichen Planus and its potencial for malignancy

Objetivos: Instruir e orientar ao cirurgião dentista e demais profissionais de saúde a importância da detecção e rastreio precoce de lesões pré-malignas. Revisão de Literatura: O Líquen Plano Oral é uma condição dermatológica crônica, de origem auto-imune, relativamente comum na população, que atinge o epitélio de mucosa e pele, sendo considerada, pela Organização Mundial de Saúde (OMS), uma desordem potencialmente maligna quando associado a áreas de ulceração. A revisão de literatura foi realizada nas bases de dados PubMed e Lilacs. Buscamos investigar o potencial de malignização do Líquen Plano Oral associado a condições erosivas, analisando o processo de carcinogênese no processo inflamatório. Conclusão: Conclui-se que o objeto de estudo ainda é um assunto pouco explorado pela literatura, porém há indícios etiopatológicos que enfatizam o processo de malignização oriundo de uma lesão pré-maligna como o Líquen Plano Oral. Além disso, enfatizamos a importância do diagnóstico precoce das lesões estomatognáticas, para que assim possamos aumentar as chances de cura do paciente.(AU)

Objectives: To instruct and guide dentists and other health professionals on the importance of early detection and screening of pre-malignant lesions. Literature Review: Oral Lichen Planus is a chronic dermatological condition, of autoimmune origin, relatively common in the population, which affects the epithelium of the mucosa and skin, being considered, by the World Health Organization (WHO), a potentially fatal disorder. malignant when associated with areas of ulceration. A literature review was performed on the PubMed and Lilacs databases. We sought to investigate the potential for malignancy of Oral Lichen Planus associated with erosive conditions, analyzing the process of carcinogenesis in the inflammatory process. Conclusion: It is concluded that the object of study is still a subject little explored in the literature, but there are etiopathological accusations that emphasize the process of malignancy arising from a pre-malignant lesion such as Oral Lichen Planus. In addition, we emphasize the importance of early diagnosis of stomatognathic lesions, so that we can increase the patient's chances of cure.(AU)

Comparative Assessment of E-cadherin's Expression between the Metastatic and Non-metastatic Oral Squamous Cell Carcinoma: An Immunohistochemical Study

ABSTRACT Objective: To identify the clinicopathological correlation of E-cadherin expression in metastatic and non-metastatic oral squamous cell carcinoma (OSCC). Material and Methods: A total of 90 paraffin-embedded tissue sections of OSCC were retrieved from the registry. The total selected samples were 45 cases each from the primary lesions of metastatic and non-metastatic OSCC. One section was subjected to routine Hematoxylin and eosin stain and another to immunohistochemical analysis for E-cadherin expression. Results: A non-significant (p˃0.05) increased expression is seen in the non-metastatic group compared to the metastatic group, with predominantly membrane as the staining site in either group. However, the expression of E-cadherin did not reveal any statistically significant association with independent variables such as age, gender, and adverse habits of the patients (p>0.05). On the other hand, with respect to the histological differentiation of OSCC, a significant association (p<0.001) was observed with the well-differentiated type of metastatic OSCC. Conclusion: E-cadherin was useful to some extent in predicting regional metastasis. However, further studies using a panel of biomarkers with increased sample size may help us understand the process involved in metastasis.

Characteristics of lymph node metastasis of right recurrent laryngeal nerve in thoracic esophageal squamous cell carcinoma / 中华肿瘤杂志

Objective: To understand the characteristics and influencing factors of lymph node metastasis of the right recurrent laryngeal nerve in thoracic esophageal squamous cell carcinoma (ESCC), and to explore the reasonable range of lymph node dissection and the value of right recurrent laryngeal nerve lymph node dissection. Methods: The clinicopathological data with thoracic ESCC were retrospectively analyzed, and the characteristics of lymph node metastasis along the right recurrent laryngeal nerve and its influencing factors were explored. Results: Eighty out of 516 patients had lymph node metastasis along the right recurrent laryngeal nerve, the metastasis rate was 15.5%. Among 80 patients with lymph node metastasis along the right recurrent laryngeal nerve, 25 cases had isolated metastasis to the right recurrent laryngeal nerve lymph node but no other lymph nodes. The incidence of isolated metastasis to the recurrent laryngeal nerve lymph node was 4.8% (25/516). A total of 1 127 lymph nodes along the right recurrent laryngeal nerve were dissected, 115 lymph nodes had metastasis, and the degree of lymph node metastasis was 10.2%. T stage, degree of tumor differentiation and tumor location were associated with right paraglottic nerve lymph node metastasis (all P<0.05). The lymph node metastasis rate along the right recurrent laryngeal in patients with upper thoracic squamous cell carcinoma (23.4%, 26/111) was higher than that of patients with middle (13.5%, 40/296) and lower (12.8%, 14/109) thoracic squamous cell carcinoma (P=0.033). In patients with poorly differentiated ESCC (20.6%, 37/180) the metastasis rate was higher than that of patients with moderately (14.6%, 39/267) and well-differentiated (5.8%, 4/69; P<0.05). The lymph node metastasis rate of patients with stage T4 (27.3%, 3/11) was higher than that of patients with stage T1 (9.6%, 19/198), T2 (19.0%, 16/84) and T3 (18.8%, 42/1 223; P<0.05). Multivariate regression analysis showed that tumor location (OR=0.61, 95% CI: 0.41-0.90, P=0.013), invasion depth (OR=1.46, 95% CI: 1.11-1.92, P=0.007), and differentiation degree (OR=1.67, 95% CI: 1.13-2.49, P=0.011) were independent risk factors for lymph node metastasis along right recurrent laryngeal nerve of ESCC. Conclusions: The lymph node along the right recurrent laryngeal nerve has a higher rate of metastasis and should be routinely dissected in patients with ESCC. Tumor location, tumor invasion depth, and differentiation degree are risk factors for lymph node metastasis along right recurrent laryngeal nerve in patients with ESCC.

Correlation and clinical significance of VISTA expression and cervical squamous cell carcinoma / 中华肿瘤杂志

Objective: To explore the relationship between the expression of the T-cell activation suppressor-immunoglobulin variable region (VISTA) and the development of cervical squamous cell carcinoma (CSCC), and the impact on the prognosis of CSCC patients. Methods: Cervical tissue samples from 116 CSCC, including 23 cervical intraepithelial neoplasia (CIN) grade I, 23 CIN grade Ⅱ-Ⅲ, and 23 chronic cervicitis patients, were collected from the First Hospital of Soochow University between March 2014 and April 2019. The expression of VISTA in each group was detected by immunohistochemistry (IHC). Survival data of CSCC patients were obtained by follow-up. The survival analysis was performed by Kaplan-Meier method, and survival differences between groups were compared by Log rank test. Prognostic impact factors were analyzed using a multifactorial Cox proportional hazards model. Results: The positive rate of VISTA expression in CSCC group was 32.8% (38/116), and which of grade Ⅱ-Ⅲ was 17.4% (4/23). VISTA expression results showed no positive expression patients in the cervical intraepithelial neoplasia grade I and chronic cervicitis groups. The differences between the CSCC group and other groups were statistically significant (P<0.01). In 116 CSCC patients, VISTA expression was associated with International Federation of Gynecology and Obstetrics (FIGO) stage and lymph node metastasis (P<0.01). The mean survival time of patients in the VISTA positive expression group was 30.7 months, and the 3-year survival rate was 44.7% (17/38). However, the mean survival time of the patients in the VISTA negative expression group was 49.1 months, and the 3-year survival rate was 87.2% (68/78). The Cox regression model found that VISTA expression positivity (P=0.001) and FIGO stage (P=0.047) were prognostic factors for CSCC, and patients with VISTA-positive CSCC had a 4.130-fold risk of death higher than those with VISTA-negative expression. Conclusions: The VISTA protein is highly expressed in CSCC tissues, and its expression level is closely related to the occurrence and development of CSCC. The expression of VISTA can be used as an independent predictor of CSCC prognosis and can provide a strong basis for the treatment of CSCC with immune checkpoint inhibitors.

Efficacy of surgical comprehensive therapy for 456 cases of hypopharyngeal carcinoma / 中华耳鼻咽喉头颈外科杂志

Objective: To retrospectively analyse the efficacy of surgerical comprehensive treatment for hypopharyngeal cancer. Methods: Four hundred and fifty-six cases of hypopharyngeal squamous cell carcinoma treated from Jan 2014 to Dec 2019 were analyzed retrospectively, including 432 males and 24 females, aged 37-82 years old. There were 328 cases of pyriform sinus carcinoma, 88 cases of posterior pharyngeal wall carcinoma, and 40 cases of postcricoid carcinoma. According to American Joint Committe on Cancer(AJCC) 2018 criteria, 420 cases were of stage Ⅲ or Ⅳ; 325 cases were of T3 or T4 stage. Treatment methods included surgery alone in 84 cases, preoperative planned radiotherapy plus surgery in 49 cases, surgery plus adjuvant radiotherapy or concurrent chemoradiotherapy in 314 cases, and inductive chemotherapy plus surgery and adjuvant radiotherapy in 9 cases. The primary tumor resection methods included transoral laser surgery in 5 cases, partial laryngopharyngectomy in 74 cases, of them 48 cases (64.9%) presented with supracricoid hemilaryngopharyngectomy, total laryngectomy with patial pharyngectomy in 90 cases, total laryngopharyngectomy or with cervical esophagectomy in 226 cases, and total laryngopharyngectomy with total esophagectomy in 61 cases. Among 456 cases, 226 cases received reconstruction surgery with free jejunum transplantation, 61 cases with gastric pull-up, and 32 cases with pectoralis myocutaneous flaps. All patients underwent retropharyngeal lymph node dissection, and high-definition gastroscopy was performed during admission and follow-up. SPSS 24.0 software was used to analyze the data. Results: The 3-year and 5-year overall survival rates were respectively 59.8%, and 49.5%. The 3-year and 5-year disease specific survival rates were respectively 69.0% and 58.8%. Total metastasis rate of retropharyngeal lymph nodes was 12.7%. A total of 132 patients (28.9%) suffered from simultaneous and metachronous multiple primary carcinoma of the hypopharynx. Multivariate Logistic regression analysis showed that T3-4 disease, cervical lymph node metastasis, retropharyngeal lymph node metastasis and postoperative adjuvant radiotherapy were independent factors affecting the prognosis of patients (all P<0.05). As of April 30, 2022, a total of 221 patients died during follow-up, of 109 (49.3%) with distant metastases, which were the main cause of death. Conclusions: The efficacy of comprehensive treatment for hypopharyngeal cancer can be improved by accurate preoperative evaluation, improved surgical resection, active retropharyngeal lymph node dissection and full process intervention of the second primary cancer.

Optimization of perioperative treatment strategies for locally advanced esophageal squamous cell carcinoma from the perspective of tumor heterogeneity / 中华胃肠外科杂志

Recent advances in multimodality treatment offer excellent opportunities to rethink the paradigm of perioperative management for locally advanced esophageal squamous cell carcinoma. One treatment clearly doesn't fit all in terms of a broad disease spectrum. Individualized treatment of local control of bulky primary tumor burden (advanced T stage) or systemic control of nodal metastatic tumor burden (advanced N stage) is essential. Given that clinically applicable predictive biomarkers are still awaited, therapy selection guided by diverse phenotypes of tumor burden (T vs. N) is promising. Potential challenges regarding the use of immunotherapy may also boost this novel strategy in the future.

Treatment and prognosis analysis of 488 patients with FIGO 2018 stage Ⅲc squamous cervical cancer / 中华妇产科杂志

Objective: To analyze the treatment and prognosis of patients with International Federation of Gynecology and Obstetrics (FIGO) 2018 stage Ⅲc cervical squamous cell carcinoma. Methods: A total of 488 patients at Zhejiang Cancer Hospital between May, 2013 to May, 2015 were enrolled. The clinical characteristics and prognosis were compared according to the treatment mode (surgery combined with postoperative chemoradiotherapy vs radical concurrent chemoradiotherapy). The median follow-up time was (96±12) months ( range time from 84 to 108 months). Results: (1) The data were divided into surgery combined with chemoradiotherapy group (surgery group) and concurrent chemoradiotherapy group (radiotherapy group), including 324 cases in the surgery group and 164 cases in the radiotherapy group. There were significant differences in Eastern Cooperation Oncology Group (ECOG) score, FIGO 2018 stage, large tumors (≥4 cm), total treatment time and total treatment cost between the two groups (all P<0.01). (2) Prognosis: ① for stage Ⅲc1 patients, there were 299 patients in the surgery group with 250 patients survived (83.6%). In the radiotherapy group, 74 patients survived (52.9%). The difference of survival rates between the two groups was statistically significant (P<0.001). For stage Ⅲc2 patients, there were 25 patients in surgery group with 12 patients survived (48.0%). In the radiotherapy group, there were 24 cases, 8 cases survived, the survival rate was 33.3%. There was no significant difference between the two groups (P=0.296). ② For patients with large tumors (≥4 cm) in the surgery group, there were 138 patients in the Ⅲc1 group with 112 patients survived (81.2%); in the radiotherapy group, there were 108 cases with 56 cases survived (51.9%). The difference between the two groups was statistically significant (P<0.001). Large tumors accounted for 46.2% (138/299) vs 77.1% (108/140) in the surgery group and radiotherapy group. The difference between the two groups was statistically significant (P<0.001). Further stratified analysis, a total of 46 patients with large tumors of FIGO 2009 stage Ⅱb in the radiotherapy group were extracted, and the survival rate was 67.4%, there was no significant difference compared with the surgery group (81.2%; P=0.052). ③ Of 126 patients with common iliac lymph node, 83 patients survived, with a survival rate of 65.9% (83/126). In the surgery group, 48 patients survived and 17 died, with a survival rate of 73.8%. In the radiotherapy group, 35 patients survived and 26 died, with a survival rate of 57.4%. There were no significant difference between the two groups (P=0.051). (3) Side effects: the incidence of lymphocysts and intestinal obstruction in the surgery group were higher than those in the radiotherapy group, and the incidence of ureteral obstruction and acute and chronic radiation enteritis were lower than those in the radiotherapy group, and there were statistically significant differences (all P<0.01). Conclusions: For stage Ⅲc1 patients who meet the conditions for surgery, surgery combined with postoperative adjuvant chemoradiotherapy and radical chemoradiotherapy are acceptable treatment methods regardless of pelvic lymph node metastasis (excluding common iliac lymph node metastasis), even if the maximum diameter of the tumor is ≥4 cm. For patients with common iliac lymph node metastasis and stage Ⅲc2, there is no significant difference in the survival rate between the two treatment methods. Based on the duration of treatment and economic considerations, concurrent chemoradiotherapy is recommended for the patients.

Analysis of risk factors for depth of invasion and angiolymphatic invasion for circumferential superficial esophageal squamous cell carcinoma and precancerous lesion / 中华肿瘤杂志

Objective: To analyze clinicopathological features of circumferential superficial esophageal squamous cell carcinoma and precancerous lesions and investigate the risk factors for deep submucosal invasion and angiolymphatic invasion retrospectively. Methods: A total of 116 cases of esophageal squamous epithelial high-grade intraepithelial neoplasia or squamous cell carcinoma diagnosed by gastroscopy, biopsy pathology and endoscopic resection pathology during November 2013 to October 2021 were collected, and their clinicopathological features were analyzed. The independent risk factors of deep submucosal invasion and angiolymphatic invasion were analyzed by logistic regression model. Results: The multivariate logistic regression analysis showed that drinking history (OR=3.090, 95% CI: 1.165-8.200; P<0.05), The AB type of intrapapillary capillary loop (IPCL) (OR=11.215, 95% CI: 3.955-31.797; P<0.05) were the independent risk factors for the depth of invasion. The smoking history (OR=5.824, 95% CI: 1.704-19.899; P<0.05), the presence of avascular area (AVA) (OR=3.393, 95% CI: 1.285-12.072; P<0.05) were the independent factors for the angiolymphatic invasion. Conclusions: The risk of deep submucosal infiltration is greater for circumferential superficial esophageal squamous cell carcinoma patients with drinking history and IPCL type B2-B3 observed by magnifying endoscopy, while the risk of angiolymphatic invasion should be vigilant for circumferential superficial esophageal squamous cell carcinoma patients with smoking history and the presence of AVA observed by magnifying endoscopy. Ultrasound endoscopy combined with narrowband imagingand magnification endoscopy can improve the accuracy of preoperative assessment of the depth of infiltration of superficial squamous cell carcinoma and precancerous lesions and angiolymphaticinvasion in the whole perimeter of the esophagus, and help endoscopists to reasonably grasp the indications for endoscopic treatment.

Progress in the relationship between head and neck squamous cell carcinom and the microbial community / 临床耳鼻咽喉头颈外科杂志

Microorganisms are one of the important factors which maintain the homeostasis of human health. Despite recent advances, the relationship between microorganisms and head and neck squamous cell carcinoma （HNSCC） is still unclear, and the impact of microorganisms on the incidence and prognosis of HNSCC cannot be neglected. Therefore, this article provides a systematic and comprehensive review summarizing the epidemiological evidence of microbial dysbiosis related to HNSCC and discusses the associations between them.

LIMP-2 enhances cancer stem-like cell properties by promoting autophagy-induced GSK3β degradation in head and neck squamous cell carcinoma / 国际口腔科学杂志·英文版

Cancer stem cell-like cells (CSCs) play an integral role in the heterogeneity, metastasis, and treatment resistance of head and neck squamous cell carcinoma (HNSCC) due to their high tumor initiation capacity and plasticity. Here, we identified a candidate gene named LIMP-2 as a novel therapeutic target regulating HNSCC progression and CSC properties. The high expression of LIMP-2 in HNSCC patients suggested a poor prognosis and potential immunotherapy resistance. Functionally, LIMP-2 can facilitate autolysosome formation to promote autophagic flux. LIMP-2 knockdown inhibits autophagic flux and reduces the tumorigenic ability of HNSCC. Further mechanistic studies suggest that enhanced autophagy helps HNSCC maintain stemness and promotes degradation of GSK3β, which in turn facilitates nuclear translocation of β-catenin and transcription of downstream target genes. In conclusion, this study reveals LIMP-2 as a novel prospective therapeutic target for HNSCC and provides evidence for a link between autophagy, CSC, and immunotherapy resistance.

Down-regulation of DNA key protein-FEN1 inhibits OSCC growth by affecting immunosuppressive phenotypes via IFN-γ/JAK/STAT-1 / 国际口腔科学杂志·英文版

Oral squamous cell carcinoma (OSCC) escape from the immune system is mediated through several immunosuppressive phenotypes that are critical to the initiation and progression of tumors. As a hallmark of cancer, DNA damage repair is closely related to changes in the immunophenotypes of tumor cells. Although flap endonuclease-1 (FEN1), a pivotal DNA-related enzyme is involved in DNA base excision repair to maintain the stability of the cell genome, the correlation between FEN1 and tumor immunity has been unexplored. In the current study, by analyzing the clinicopathological characteristics of FEN1, we demonstrated that FEN1 overexpressed and that an inhibitory immune microenvironment was established in OSCC. In addition, we found that downregulating FEN1 inhibited the growth of OSCC tumors. In vitro studies provided evidence that FEN1 knockdown inhibited the biological behaviors of OSCC and caused DNA damage. Performing multiplex immunohistochemistry (mIHC), we directly observed that the acquisition of critical immunosuppressive phenotypes was correlated with the expression of FEN1. More importantly, FEN1 directly or indirectly regulated two typical immunosuppressive phenotype-related proteins human leukocyte antigen (HLA-DR) and programmed death receptor ligand 1 (PD-L1), through the interferon-gamma (IFN-γ)/janus kinase (JAK)/signal transducer and activator transcription 1 (STAT1) pathway. Our study highlights a new perspective on FEN1 action for the first time, providing theoretical evidence that it may be a potential immunotherapy target for OSCC.

Prognostic value of pre-operative peripheral inflammation markers in patients with squamous cell carcinoma of the external auditory canal / Valor prognóstico dos marcadores de inflamação periférica pré-operatórios em pacientes com carcinoma espinocelular do meato acústico externo

Abstract Introduction: Squamous cell carcinoma of the external auditory canal is a rare entity. Previous studies have suggested predictors for tumor recurrence. However, most of the prognostic factors were from the clinicopathological aspect. Objective: This study aims to analyze the correlation between pre-operative peripheral inflammation markers and survival outcomes, in order to identify prognostic biomarkers for patients with squamous cell carcinoma of the external auditory canal. Methods: We retrospectively analyzed patients diagnosed with squamous cell carcinoma of the external auditory canal who underwent surgery at our institute. The pre-operative circulating inflammatory markers, such as the neutrophil, lymphocyte, platelet, and monocyte counts were measured and their ratios including neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and lymphocyte-to-monocyte ratio were calculated. The prognostic value of the measured hematologic parameters in relation to the survival outcomes was also evaluated. Results: A total of 83 patients were included, of which 26 patients showed tumor recurrence and 57 without recurrence. Neutrophil counts and neutrophil-to-lymphocyte ratio were closely connected with tumor stage. In the patients with recurrence, neutrophil counts, neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio were elevated (p< 0.0001, p< 0.0001 and p = 0.001), while lymphocyte counts and lymphocyte-to-monocyte ratio were decreased (p = 0.013 and p = 0.016, respectively). The receiver operating curve analysis indicated that pre-operative neutrophil-to-lymphocyte ratio is a potential prognostic marker for recurrence of squamous cell carcinoma of the external auditory canal (area under curve = 0.816), and the cut-off points was 2.325. Conclusions: Pre-operative neutrophil and lymphocyte counts, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, lymphocyte-to-monocyte are significantly correlated with tumor recurrence in patients with external auditory canal squamous cell carcinoma. Furthermore, neutrophil-to-lymphocyte ratio may be unfavorable prognostic factors of this disease.

Resumo Introdução: O carcinoma espinocelular do meato acústico externo é uma doença rara. Estudos anteriores sugeriram preditores de recorrência do tumor. Entretanto, a maioria dos fatores prognósticos se originou do aspecto clínico-patológico. Objetivo: Analisar a correlação entre marcadores inflamatórios periféricos pré-operatórios e os desfechos de sobrevida e identificar biomarcadores prognósticos para pacientes com carcinoma espinocelular do meato acústico externo. Método: Analisamos retrospectivamente pacientes com diagnóstico de carcinoma espinocelular do meato acústico externo submetidos à cirurgia em nosso instituto. Os marcadores inflamatórios circulantes pré-operatórios, como as contagens de neutrófilos, linfócitos, plaquetas e monócitos, foram medidos e as suas relações calculadas, inclusive as relações neutrófilos/linfócitos, plaquetas/linfócitos e linfócitos/monócitos. O valor prognóstico dos parâmetros hematológicos medidos em relação aos desfechos de sobrevida também foi avaliado. Resultados: Foram incluídos 83 pacientes, entre os quais 26 apresentaram recorrência tumoral e 57 não apresentaram. A contagem de neutrófilos e a relação neutrófilo/linfócito estavam intimamente associadas ao estágio do tumor. Nos pacientes com recorrência, a contagem de neutrófilos, a relação neutrófilos/linfócitos e a relação plaquetas/linfócitos eram elevadas (p < 0,0001, p > 0,0001 e p = 0,001), enquanto a contagem de linfócitos e a relação linfócitos/monócitos estavam diminuídas (p = 0,012 ep = 0,016, respectivamente). A análise da curva, Receiver Operating Characteristic, indicou que a relação neutrófilos/linfócitos pré-operatória era um potencial marcador prognóstico para a recorrência de carcinoma espinocelular do meato acústico externo (Área sob a curva = 0,816) e o ponto de corte foi de 2,325. Conclusão: A contagem pré-operatória de neutrófilos e linfócitos, as relações neutrófilos/linfócitos, plaquetas/linfócitos e linfócitos/monócitos estão significativamente correlacionadas com a recorrência do tumor em pacientes com carcinoma espinocelular do meato acústico externo. Além disso, a relação neutrófilos/linfócitos pode ser um fator prognóstico desfavorável dessa doença.

Carcinoma of the posterior wall of the hypopharynx: surgical treatment with larynx preservation / Carcinoma da parede posterior da hipofaringe: tratamento cirúrgico com preservação da laringe

Abstract Introduction: Posterior pharyngeal wall is the most rare subsite for hypopharyngeal carcinomas. Because of its rarity, there are few studies published in the literature specifically concerning posterior pharyngeal wall carcinoma. Objectives: To report our functional results in patients with the carcinoma of the posterior wall of the hypopharynx after surgical treatment by resection via a lateral or infrahyoid pharyngotomy approach, with the preservation of the larynx and reconstruction with a radial forearm free flap. Methods: The study included 10 patients who underwent surgery for a carcinoma of the posterior wall of the hypopharynx over a 6 year period. The associated postoperative morbidity was investigated and functional results were analyzed. Results: Nine patients had T3 lesions and one patient had a T2 lesion. The preferred approach to access the hypopharynx was a lateral pharyngotomy in 5 patients and lateral pharyngotomy combined with infrahyoid pharyngotomy in 5 patients with superior extension to oropharynx. The pharyngeal defects were reconstructed successfully with radial forearm free flaps. Four patients received adjuvant radiotherapy only, and 4 patients with N2b and N2c neck diseases received adjuvant chemoradiotherapy. The mean duration of hospitalization was 15.6 days (range, 10-21 days). All patients achieved oral intake in a median time of 74 days (range, 15-180). Decannulation was achieved in all patients and the median time fordecannulation was 90 (range, 21-300 days). The mean followup duration was 38.3 months (range, 10-71 months) and 8 patients survived. One patient died due to regional recurrence in the retropharyngeal lymph nodes and 1 patient died due to systemic metastasis. Conclusion: Primary surgery is still a very effective treatment modality for the carcinoma of the posterior wall of the hypopharynx and does not permanently compromise the swallowing and laryngeal functions if pharyngeal reconstruction is performed with a free flap.

Resumo Introdução: A parede posterior da faringe é o subsítio mais raro para carcinomas hipofaríngeos. Devido à sua raridade, há poucos estudos publicados na literatura especificamente sobre o carcinoma da parede posterior da faringe. Objetivo: Relatar nossos resultados funcionais em pacientes com carcinoma da parede posterior da hipofaringe após tratamento cirúrgico por ressecção via faringotomia lateral ou infra-hióidea, com preservação da laringe e reconstrução com retalho livre radial do antebraço. Método: O estudo incluiu 10 pacientes submetidos à cirurgia para carcinoma da parede posterior da hipofaringe por 6 anos. A morbidade pós-operatória associada foi investigada e os resultados funcionais foram analisados. Resultados: Nove pacientes apresentaram lesões T3 e um paciente apresentou lesão T2. Avia preferida para acessar a hipofaringe foi a faringotomia lateral em 5 pacientes e a faringotomia lateral combinada com a faringotomia infra-hióidea em 5 pacientes com extensão superior até a orofaringe. Os defeitos faríngeos foram reconstruídos com sucesso com retalhos livres radiais do antebraço. Quatro pacientes receberam apenas radioterapia adjuvante e 4 pacientes com doença cervical N2b e N2c receberam quimiorradioterapia adjuvante. A duração média da hospitalização foi de 15,6 dias (variação de 10 a 21 dias). Todos os pacientes retornaram à ingestão oral em um tempo médio de 74 dias (variação de 15 a 180). A decanulação foi possível para todos os pacientes e o tempo médio foi de 90 dias (variação de 21 a 300 dias). A duração média do seguimento foi de 38,3 meses (10 a 71 meses) e 8 pacientes sobreviveram. Um paciente foi a óbito devido a recorrência regional nos linfonodos retrofaríngeos e outro devido a metástase sistêmica. Conclusão: A cirurgia primária ainda é uma modalidade de tratamento muito eficaz para o carcinoma da parede posterior da hipofaringe e não compromete de forma permanente as funções de deglutição e da laringe se a reconstrução faríngea for feita com retalho livre.

Biomarcadores da transição epitélio-mesenquimal em desordens potencialmente malignas e carcinoma de células escamosas de língua oral / Biomarkers of epithelial-mesenchymal transition in potentially malignant disorders and squamous cell carcinoma of the oral tongue

Durante a carcinogênese oral, as células malignas adquirem um fenótipo agressivo que resulta em aumento da motilidade individual e na capacidade para invadir tecidos circunvizinhos. Para tanto, as células epiteliais malignas desenvolvem um processo regulatório e programado denominado transição epitélio-mesenquimal (TEM), que é crucial para aquisição deste fenótipo maligno agressivo. O objetivo do presente estudo foi investigar o papel da expressão imunoistoquímica de proteínas sinalizadoras da TEM em displasias epiteliais orais e em carcinomas de células escamosas de língua oral (CCELO), avaliando suas respectivas associações com parâmetros clínico-patológicos e de prognóstico. Inicialmente, objetivando obter uma compreensão aprofundada sobre o tema proposto, foram desenvolvidas duas revisões sistemáticas de literatura avaliando o papel da TEM como possível marcador de prognóstico em casos diagnosticados como displasia epitelial oral e o papel dos fatores de transcrição nuclear associados ao processo de TEM na regulação da plasticidade celular e no compartamento biológico em linhagens celulares de carcinoma de células escamosas em região de cabeça e pescoço. Para o estudo imunoistoquímico, foram selecionados 47 casos de displasias epiteliais orais e 41 casos diagnosticados como CCELO, nos quais foram analisados a imunoexpressão das proteínas Twist1, Snail1, E-caderina e N-caderina. Foram investigadas possíveis associações entre o padrão de expressão destas proteínas com a gradação histopatológica das displasias epiteliais e com os aspectos clínico-patológicos, recidiva e sobrevida em CCELO. Foram observados diferentes padrões de marcação entre os grupos analisados, observando-se uma perda significativa da expressão da E-caderina membranar em casos de CCELO em comparação aos casos de displasias epiteliais orais (p = <0.0001). Foi observado uma pior sobrevida global em casos com baixa expressão da E-caderina membranar (HR = 0.27; p = 0.033) e alta expressão do Twist1 citoplasmático (HR = 3.19; p = 0.010). Ao analisar isoladamente o parâmetro intensidade de expressão, foi observada associação entre a alta intensidade da N-caderina citoplasmática com a sobrevida global (HR = 4.93; p = 0.006). Nossos achados sugerem que a perda da expressão da E-caderina e o aumento da expressão da N-caderina e dos fatores de transcrição nuclear Twist1 e Snail1 estão associados ao desenvolvimento e progressão da carcinogênese oral. Isoladamente, a perda da expressão membranar da E-caderina e o aumento da expressão citoplasmática do Twist1 e da N-caderina foram associados a uma pior sobrevida (AU).

During oral carcinogenesis, malignant cells acquire an aggressive phenotype that results in increased individual motility and the ability to invade surrounding tissues. Therefore, malignant epithelial cells develop a regulatory and programmed process called epithelial-mesenchymal transition (EMT), which is crucial for the acquisition of this aggressive malignant phenotype. The aim of the present study was to investigate the role of immunohistochemical expression of EMT signaling proteins in oral epithelial dysplasias and oral squamous cell carcinomas of the tongue (OTSCC), evaluating their respective associations with clinicopathological and prognostic parameters. Initially, aiming to obtain a deeper understanding of the proposed topic, two systematic literature reviews were developed evaluating the role of EMT as a possible prognostic marker in cases diagnosed as oral epithelial dysplasia and the role of nuclear transcription factors associated with the MET process in regulation of cellular plasticity and biological behavior in head and neck squamous cell carcinoma cell lines. For the immunohistochemical study, 47 cases of oral epithelial dysplasias and 41 cases diagnosed with OTSCC were selected, in which the immunoexpression of Twist1, Snail1, E-cadherin and Ncadherin proteins were analyzed. Possible associations between the expression pattern of these proteins and the histopathological grading of epithelial dysplasias and with the clinicopathological aspects, recurrence and survival in OTSCC were investigated. Different staining patterns were observed between the analyzed groups, with a significant loss of membrane E-cadherin expression in cases of OTSCC compared to cases of oral epithelial dysplasias (p = <0.0001). Worse overall survival was observed in cases with low membrane E-cadherin expression (HR = 0.27; p = 0.033) and high cytoplasmic Twist1 expression (HR = 3.19; p = 0.010). When analyzing the expression intensity parameter alone, an association was observed between high cytoplasmic N-cadherin intensity and overall survival (HR = 4.93; p = 0.006). Our findings suggest that loss of E-cadherin expression and increased expression of N-cadherin and nuclear transcription factors Twist1 and Snail1 are associated with the development and progression of oral carcinogenesis. Alone, loss of membrane expression of E-cadherin and increased cytoplasmic expression of Twist1 and N-cadherin were associated with worse survival (AU).

The enhanced genomic 6 mA metabolism contributes to the proliferation and migration of TSCC cells / 国际口腔科学杂志·英文版

In contrast to the well-established genomic 5-methylcytosine (5mC), the existence of N6-methyladenine (6 mA) in eukaryotic genomes was discovered only recently. Initial studies found that it was actively regulated in cancer cells, suggesting its involvement in the process of carcinogenesis. However, the contribution of 6 mA in tongue squamous cell carcinoma (TSCC) still remains uncharacterized. In this study, a pan-cancer type analysis was first performed, which revealed enhanced 6 mA metabolism in diverse cancer types. The study was then focused on the regulation of 6 mA metabolism, as well as its effects on TSCC cells. To these aspects, genome 6 mA level was found greatly increased in TSCC tissues and cultured cells. By knocking down 6 mA methylases N6AMT1 and METTL4, the level of genomic 6 mA was decreased in TSCC cells. This led to suppressed colony formation and cell migration. By contrast, knockdown of 6 mA demethylase ALKBH1 resulted in an increased 6 mA level, enhanced colony formation, and cell migration. Further study suggested that regulation of the NF-κB pathway might contribute to the enhanced migration of TSCC cells. Therefore, in the case of TSCC, we have shown that genomic 6 mA modification is involved in the proliferation and migration of cancer cells.

Primary ovarian squamous cell carcinoma: clinicopathological features and prognostic analysis of fifteen cases / 中华病理学杂志

Objective: To assess the clinical features and treatment outcomes in patients with primary ovarian squamous cell carcinoma (POSCC). Methods: Fifteen patients with primary ovarian squamous cell carcinoma diagnosed from January 2009 to December 2018 in Cancer Hospital of the University of Chinese Academy of Sciences were collected. The expression of p16, hMLH1, hMSH2, hMSH6 and PMS2 in POSCC was detected by immunohistochemistry, and the status of high-risk human papillomavirus (HPV) by RNAscope test. Results: Squamous cell carcinoma with different degrees of differentiation was found in 15 cases, including three cases with high differentiation and 12 cases with medium to low differentiation. There were four cases with in situ squamous cell carcinoma, four cases with teratoma, one case with endometrial carcinoma/atypical hyperplasia, and one case with endometriosis. p16 was expressed in five cases (5/15), indicating coexisting high-risk HPV infection. There was no high-risk HPV infection in the remaining 10 cases, and p16 staining was negative. There was no deficient mismatch repair protein in all cases. The overall survival time (P=0.038) and progression free survival (P=0.045) of patients with high-risk HPV infection were longer than those without HPV infection. Conclusions: POSCC is more commonly noted in postmenopausal women and often occurs unilaterally. Elevated serological indexes CA125 and SCC are the most common finding. Morphologically, the tumors show variable degrees of differentiation, but the current data suggest that the degree of differentiation cannot be used as an independent prognostic index. High-risk HPV infection may be associated with the occurrence of POSCC, and that the prognosis of POSCC patients with HPV infection is better than that of patients without infection.

Cancer cells corrupt normal epithelial cells through miR-let-7c-rich small extracellular vesicle-mediated downregulation of p53/PTEN / 国际口腔科学杂志·英文版

Tumor volume increases continuously in the advanced stage, and aside from the self-renewal of tumor cells, whether the oncogenic transformation of surrounding normal cells is involved in this process is currently unclear. Here, we show that oral squamous cell carcinoma (OSCC)-derived small extracellular vesicles (sEVs) promote the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of normal epithelial cells but delay their apoptosis. In addition, nuclear-cytoplasmic invaginations and multiple nucleoli are observed in sEV-treated normal cells, both of which are typical characteristics of premalignant lesions of OSCC. Mechanistically, miR-let-7c in OSCC-derived sEVs is transferred to normal epithelial cells, leading to the transcriptional inhibition of p53 and inactivation of the p53/PTEN pathway. In summary, we demonstrate that OSCC-derived sEVs promote the precancerous transformation of normal epithelial cells, in which the miR-let-7c/p53/PTEN pathway plays an important role. Our findings reveal that cancer cells can corrupt normal epithelial cells through sEVs, which provides new insight into the progression of OSCC.

Cell heterogeneity of laryngeal carcinoma and evolution trajectory of epithelial cells / 中华耳鼻咽喉头颈外科杂志

Objective: To analyze the classification and functions of cell subsets in laryngeal carcinoma and metastatic lymph nodes, and to explore the evolution trajectory of epithelial cells to tumor cells. Methods: Single-cell RNA sequencing was performed on 5 cases of laryngeal cancer, matched metastatic lymph nodes and 3 normal tissues. Patients were admitted to Ningbo Medical Center Lihuili Hospital from October 22, 2019 to December 16, all patients were male, aged 53-70 years old. Cell subsets of the above-mentioned tissues were analyzed by the Seurat, and the biological functions of cell subpopulation were investigated by functional enrichment analysis. Malignant epithelial cells were identified using copy number variation (CNV). The evolutionary trajectory of epithelial cells to cancer cells was analyzed by cell trajectory analysis, and cancerous transitional cells were identified. The highly expressed genes in transitional cells were analyzed by the FindAllMarker of the Seurat and verified by immunohistochemistry. Results: A total of 66 969 high-quality cells were obtained in 9 major clusters: epithelial cells, T cells, B cells, fibroblasts, endothelial cells, myeloid cells, mast cells, plasmacytoid dendritic cells and nerve cells. The first 5 cell clusters were divided into 8, 6, 4, 3 and 2 subgroups, respectively. Four epithelial cell subsets (C0, C1, C2 and C5) were derived from tumor tissues and metastatic lymph nodes, and had high levels of CNV and tumor cell content. Cell trajectory analysis showed that the evolution trajectory of epithelial cells was from normal epithelial subpopulation C4 to early cancerous cell population C0, which differentiated into three major malignant cell subsets C1, C3, and C5. Epithelial cell C0 may represent the transitional cell population of carcinogenesis, and were enriched in biological processes such as epithelial-mesenchymal transformation and angiogenesis. C0 highly expressed sulforaphane (SFN) which may be related to the occurrence and development of cancer. Immunohistochemistry confirmed that SFN was highly expressed in tumor tissues and metastatic lymph nodes compared with paracancerous tissues. Conclusion: Single-cell sequencing may be used to elucidate the diversity of cells and functions in laryngeal carcinoma tissues and metastatic lymph nodes, and cell population C0 plays a key role in the evolution of cells.

Carcinoma escamocelular bucal. Caso clínico y revisión de la literatura / Oral squamous cell carcinoma. Case report and review of literature

Introducción: el cáncer escamocelular (CEC) representa el 90-95% de todos los tipos de cáncer. En México, la frecuencia de CEC bucal (CECB) se ha incrementado y presenta una incidencia entre el 1 y el 5%. El CECB se asocia con sujetos en la quinta y séptima década de la vida, el sexo masculino, positivos a tabaquismo, alcoholismo, factores genéticos, inmunosupresión, infección por virus del papiloma humano (VPH) y estilos de vida poco saludables, entre otros. El objetivo de este trabajo fue presentar un caso clínico como ejemplo de las características emergentes en un paciente con CECB. Caso clínico: mujer de 38 años, con úlcera indurada, parcialmente adherida a planos profundos y dolorosa, asociada con un aumento de volumen, ubicada en vientre y borde lateral de lengua. Se realizó biopsia y con el diagnóstico histopatológico de carcinoma escamocelular invasor bien diferenciado, se procedió a determinar la presencia delVPH y resultó positivo a VPH 16. Se realizó tratamiento oncológico combinado (quirúrgico-radiación-quimioterapia), con buenos resultados para la paciente respecto a la estética y función. Conclusiones: se analizaron varios estudios que evalúan la presencia del VPH en lesiones de CECB, como un factor de riesgo que involucra con mayor frecuencia casos de pacientes jóvenes, la localización en lengua y antecedentes negativospara tabaquismo y alcoholismo frente a casos de CECB no asociados al VPH. Se requieren datos que contribuyan a dilucidar diversos aspectos aún desconocidos sobre la infección bucal por VPH y su relación con el CECB.

Background: Squamous cell cancer (SCC) represents 90-95% of all types of cancer. In Mexico, the frequency of oral SCC (OSCC) has increased, with an incidence between 1 and 5%. OSCC is associated with subjects in the 5 and 7th decade of life, males, positive for smoking, alcoholism, genetic factors, immunosuppression, human papillomavirus (HPV) infection, and unhealthy lifestyles, among others. Theobjectiveof thisworkwas to presenta clinical case as an example of the emerging characteristics in a patient with OSCC. Clinical case: 38-year-old female patient, with indurated ulcer, partially adhered to deep planes and painful, associated with an increase in volume, located on the belly and lateral edge of the tongue. A biopsy was performed and with the histopathological diagnosis of well differentiated invasive squamous cell carcinoma, the presence of HPV was determined, resulting positive for HPV-16. Combined cancer treatment was performed (surgical radiation-chemotherapy), with good results for the patient regarding aesthetics and function. Conclusions: We analyzed several studies evaluating the presence of HPV in lesions of OSCC, as a risk factor that involves more frequently cases of young patients, with location in tongue, and negative antecedents for smoking and alcoholism compared to cases of OSCC not associated with HPV. Data are required to help elucidate various still unknown aspects of oral HPV infection and its relationship with OSCC.

Perfil epidemiológico do carcinoma de células escamosas de cavidade oral e orofaringe diagnosticados na liga mossoroense de estudos e combate ao câncer / Epidemiologic Profile of squamous cell carcinoma of the oral cavity and oropharynx in the MossoróLeague for Studying and Combating Cancer / Perfil epidemiológico del carcinoma epidermoide de cavidad oral y orofaringe diagnosticado en la Liga Mossoroense de Estudios y Combate al Cáncer

Introdução:O carcinoma de células escamosas de cavidade oral e orofaringe é uma neoplasia epitelial maligna comum, respondendo pela maioria dos casos de tumores de cabeça e pescoço. Ele está relacionado a hábitos comportamentais, como tabagismo e etilismo de longa duração, e à infecção pelo Papilomavírus humano. Objetivos:Esse estudo objetivou descrever o perfil epidemiológico dos pacientes diagnosticados com essa neoplasia na Liga Mossoroense de Estudos e Combate ao Câncer. Metodologia: Foi realizado um estudo observacional com delineamento transversal a partir de dados presentes nos prontuários clínicos e laudos anatomopatológicos e no Sistema de Informações sobre Mortalidade no período entre 2006 a 2018. Os dados foram analisados a partir do Software R, utilizandoo teste de Wilcoxon-Mann-Whitney para as análises inferenciais e o método de Kaplan-Meier para análise da sobrevida. Resultados:225 prontuários foram analisados, sendo 70,22% de homens, 65,33% na faixa etária entre 46-70 anos e cor branca (51,57%). Destes, 25,78% eram tabagistas e 39,11% tabagistas e etilistas. O principal tratamento identificado foi a associação de cirurgia, quimioterapia e radioterapia. Observou-se que 49,10% dos óbitos foram em decorrência dessa neoplasia. O principal estádio patológico encontrado foi o quatro A (34,22%). Foi identificada maior sobrevida nos pacientes acima de 70 anos, cujo tratamento foi exclusivamente cirúrgico. Menor sobrevida foi identificada em indivíduos que tinham associação de hábitos (etilismo e tabagismo). Conclusões:Nossos resultados sugerem que a evolução à óbito foi o principal desfecho clínico e, isso pode estar relacionado aos hábitos comportamentais que influenciam diretamente o curso e prognóstico da doença. Ademais, destaca-se a importância do diagnóstico precoce a fim de reduzir óbitos e melhorar a qualidade de vida dos indivíduos, assim como a necessidade de implementar políticas educativas sobre os principais fatores de risco associados ao desenvolvimento dessa neoplasia (AU).

Introduction: Squamous cell carcinoma of the oral cavity and oropharynx is a common malignant epithelial neoplasm, accounting for most cases of head and neck tumors. It is related to behavioral habits, such as long-standing smoking and alcoholism, as well as to the human Papillomavirus infection. Objectives: This study aimed at describing the epidemiological profile of the patients diagnosed with this neoplasm in the Mossoró League for Studying and Combating Cancer. Methodology:An observational study with a cross-sectional design was carried out based on data present in the medical records and anatomopathological reports and in the Mortality Information System during the 2006-2018 period. The data were analyzed using the R Software, resorting to the Wilcoxon-Mann-Whitneytest for the inferential analyses and to the Kaplan-Meier method for survival analysis. Results: 225 medical records were analyzed: 70.22% belonging to men, 65.33% aged between 46 and 70 years old and white-skinned (51.57%). Of these, 25.78% were smokers and 39.11% were smokers and alcoholics. The main treatment identified was the association of surgery, chemotherapy and radiotherapy. It was observed that 49.10% of the deaths were due to this neoplasm. The main pathological stage found wasfour A(34.22%).Longer survival was identified in patients over 70 years of age, whose treatment was exclusively surgical. Shorter survival was identified in individuals who had associated habits (alcoholism and smoking). Conclusions:Our results suggest that evolution to death was the main clinical outcome; this can be related to the behavioral habits that exert a direct influence on the course and prognosis of the disease. Furthermore, the importance of early diagnosis is highlighted in order to reduce the number of deaths and improve the individuals' quality of life, as well as the need to implement educational policies on the main risk factors associated with the development of this neoplasm (AU).

Introducción: El carcinoma de células escamosas de la cavidad oral y la orofaringe es una neoplasia epitelial maligna común, que representa la mayoría de los casos de tumores de cabeza y cuello. Se relaciona con hábitos de comportamiento, como el tabaquismo y el alcoholismo, y la infección por el virus papiloma humano. Objetivos:Este estudio tuvo como objetivo describir el perfil epidemiológico de los pacientes diagnosticados con esta neoplasiaen la Liga Mossoroense de Estudios y Combate al Cáncer. Metodología: Se realizó un estudio observacional, transversal a partir de los datos presentes en las historias clínicas e informes patológicos y en el Sistema de Información de Mortalidad en el período 2006-2018. Los datos se analizaron mediante el Software R, con utilización de la Prueba de Wilcoxon-Mann-Whitney para análisis inferencial y el método de Kaplan-Meier para análisis de supervivencia. Resultados:Se analizaron 225 historias clínicas, 70,22% en hombres, 65,33% con edades entre 46-70 años y blancos (51,57%). De estos, 25,78% eran fumadores y 39,11% eran fumadores y alcohólicos. El principal tratamiento identificado fue la asociación de cirugía, quimioterapia y radioterapia. 49,10% de las muertes se debieron a esta neoplasia. El principal estadio patológico encontrado fue cuatro A (34,22%). Se identificó mayor sobrevida en pacientes mayores de 70 años, cuyo tratamiento fue exclusivamente quirúrgico. Se identificó una menor sobrevida en personas que tenían hábitos asociados. Conclusiones:Nuestros resultados sugieren que la evolución hacia la muerte fue el principal resultado clínico y esto puede estar relacionado con hábitos de comportamiento que influyen directamente en el curso y pronóstico de la enfermedad. Además, se destaca la importancia del diagnóstico precoz para reducir las muertes y mejorar la calidad de vida, así como la necesidad de implementar políticas educativas sobre los principales factores de riesgo asociados al desarrollo de esta neoplasia (AU).