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1.
BMC Surg ; 20(1): 6, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31914981

RESUMO

BACKGROUND: Head and neck surgeries can perturb normal structures of neck muscles and nerve innervations, which are supposed to function in harmony to allow complicated process like swallowing. It is still likely that cricopharyngal dysfunction emerges years after the head and neck surgeries. CASE PRESENTATION: We report a case with history of left unilateral vocal cord immobility and development of dysphagia and aspiration 2 years after radical thyroidectomy with neck lymph nodes dissection and medialization thyroplasty. Cricopharyngeal dysfunction was impressed and was confirmed with visualization of cricopharyngeal narrowing segment in radiographic contrast swallow examination. The patient was treated successfully by cricopharyngeal myotomy, achieving long-term relief in our 4 years of follow up. CONCLUSIONS: Our case of delayed cricopharyngal dysfunction after radical thyroidectomy and medialization thyroplasty shows that it is important to follow up swallowing functions after patients with UVCI undergo medialization thyroplasty. In the event of delayed manifestation of cricopharyngeal function, it can still be treated successfully by cricoharyngeal myotomy, achieving long term relief of dysphagia.


Assuntos
Transtornos de Deglutição/cirurgia , Traumatismos do Nervo Laríngeo/complicações , Miotomia/métodos , Esvaziamento Cervical/efeitos adversos , Músculos Faríngeos/cirurgia , Complicações Pós-Operatórias/cirurgia , Tireoidectomia/efeitos adversos , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/fisiopatologia , Feminino , Humanos , Traumatismos do Nervo Laríngeo/fisiopatologia , Traumatismos do Nervo Laríngeo/cirurgia , Pessoa de Meia-Idade , Músculos Faríngeos/inervação , Músculos Faríngeos/fisiopatologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/fisiopatologia
2.
Proteomics ; 17(11)2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28493537

RESUMO

We reported an integrated platform to explore serum protein variant pattern in cancer and its utility as a new class of biomarker panel for diagnosis. On the model study of serum amyloid A (SAA), we employed nanoprobe-based affinity mass spectrometry for enrichment, identification and quantitation of SAA variants from serum of 105 gastric cancer patients in comparison with 54 gastritis patients, 54 controls, and 120 patients from other cancer. The result revealed surprisingly heterogeneous and most comprehensive SAA bar code to date, which comprises 24 SAA variants including SAA1- and SAA2-encoded products, polymorphic isoforms, N-terminal-truncated forms, and three novel SAA oxidized isotypes, in which the variant-specific peptide sequence were also confirmed by LC-MS/MS. A diagnostic model was developed for dimension reduction and computational classification of the 24 SAA-variant bar code, providing good discrimination (AUC = 0.85 ± 3.2E-3) for differentiating gastric cancer group from gastritis and normal groups (sensitivity, 0.76; specificity, 0.81) and was validated with external validation cohort (sensitivity, 0.71; specificity, 0.74). Our platform not only shed light on the occurrence and modification extent of under-represented serum protein variants in cancer, but also suggested a new concept of diagnostic platform by serum protein variant profile.


Assuntos
Mucosa Gástrica/metabolismo , Gastrite/diagnóstico , Proteína Amiloide A Sérica/metabolismo , Neoplasias Gástricas/diagnóstico , Cromatografia Líquida , Diagnóstico Diferencial , Gastrite/metabolismo , Humanos , Isoformas de Proteínas , Neoplasias Gástricas/metabolismo , Espectrometria de Massas em Tandem
3.
Int J Cancer ; 141(10): 1987-1996, 2017 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-28758200

RESUMO

Esophageal squamous-cell neoplasia (ESCN) is a common second primary neoplasia found in patients with head-and-neck squamous-cell carcinoma (HNSCC). This study sought to identify the risk factors for synchronous ESCN and how they influence survival in HNSCC patient. Eight hundred and fifteen incident HNSCC patients were prospectively recruited for endoscopy screening for ESCN using white-light imaging, narrow-band imaging, Lugol chromoendoscopy, and pathological confirmation. Associated lifestyle and clinicopathological data were collected. The interquartile follow-up period cutoffs were 11.3, 20.5 and 34.9 months. 124 patients (15.2%) were diagnosed as having synchronous ESCN (66 low-grade dysplasia, 29 high-grade dysplasia, and 29 esophageal squamous-cell carcinoma). Consumption of alcohol, but not betel nut or cigarette, was significantly associated with the presence of synchronous ESCN (adjusted odds ratio [aOR] = 7.1 and 10.9 for former and current drinkers, respectively). There was an interaction between cumulative dose of alcohol consumption and alcohol flushing response on the development of ESCN. High-dose drinkers with flush response were 16.9 times more likely to have esophageal high-grade dysplasia/SCC than non-drinkers. Compared with oral cavity cancer patients, those with hypopharyngeal, laryngeal and oropharyngeal cancer were 6.8, 4.6 and 2.8 times more likely to have esophageal high-grade dysplasia/SCC. HNSCC patients with synchronous ESCN had lower overall survival than those without (p < 0.0001). In conclusion, surveillance of ESCN is strongly recommended for the high-risk subpopulation of HNSCC patients, especially drinkers who have a flush response to alcohol, and those with distant metastasis of index cancer and cancers in hypopharynx, oropharynx and larynx.


Assuntos
Carcinoma de Células Escamosas/diagnóstico , Detecção Precoce de Câncer , Endoscopia/métodos , Neoplasias Esofágicas/diagnóstico , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias Primárias Múltiplas/diagnóstico , Segunda Neoplasia Primária/diagnóstico , Adulto , Consumo de Bebidas Alcoólicas/efeitos adversos , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/etiologia , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/etiologia , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/complicações , Neoplasias de Cabeça e Pescoço/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias Primárias Múltiplas/epidemiologia , Neoplasias Primárias Múltiplas/etiologia , Segunda Neoplasia Primária/epidemiologia , Segunda Neoplasia Primária/etiologia , Prevalência , Prognóstico , Fatores de Risco , Taxa de Sobrevida , Taiwan/epidemiologia
4.
J Toxicol Environ Health A ; 79(1): 39-47, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26731659

RESUMO

DNA repair genes play critical roles in response to carcinogen-induced and anticancer therapy-induced DNA damage. Benzo[a]pyrene (BaP), the most carcinogenic polycyclic aromatic hydrocarbon (PAH), is classified as a group 1 carcinogen by International Agency for Research on Cancer. The aims of this study were to (1) evaluate the effects of BaP on DNA repair activity and expression of DNA repair genes in vitro and (2) examine the role of xeroderma pigmentosum, complementation group D (XPD) mRNA expression in human head and neck cancers. Host cell reactivation assay showed that BaP inhibited nucleotide excision repair in H1299 lung cancer cells. DNA repair through the non-homologous end-joining pathway was not affected by BaP. Real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR) and Western blot demonstrated that XPD was downregulated by BaP treatment. BaP exposure did not apparently affect expression of another 11 DNA repair genes. BaP treatment increased the DNA damage marker γ-H2AX and ultraviolet (UV) sensitivity, supporting an impairment of DNA repair in BaP-treated cells. XPD expression was also examined by quantitative RT-PCR in 68 head and neck cancers, and a lower XPD mRNA level was found in smokers' cancer specimens. Importantly, reduced XPD expression was correlated with patient 5-year overall survival rate (35 vs. 56%) and was an independent prognostic factor (hazard ratio: 2.27). Data demonstrated that XPD downregulation was correlated with BaP exposure and human head and neck cancer survival.


Assuntos
Benzo(a)pireno/toxicidade , Carcinógenos/toxicidade , Poluentes Ambientais/toxicidade , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias Pulmonares/metabolismo , Proteína Grupo D do Xeroderma Pigmentoso/biossíntese , Xeroderma Pigmentoso/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Linhagem Celular Tumoral , Reparo do DNA , Feminino , Expressão Gênica/efeitos dos fármacos , Histonas/biossíntese , Humanos , Masculino , Pessoa de Meia-Idade , RNA Neoplásico/biossíntese , RNA Neoplásico/genética , Fumar/metabolismo , Fumar/patologia , Análise de Sobrevida , Raios Ultravioleta , Proteína Grupo D do Xeroderma Pigmentoso/genética
5.
World J Surg Oncol ; 13: 24, 2015 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-25889574

RESUMO

Laryngeal schwannomas are rare, benign neurogenic tumors. They normally present as a slow-growing, encapsulated, submucosal mass in the supraglottic region. We describe a 20-year-old female presenting with a 2-year history of hoarseness and progressive worsening dyspnea. Fiberoptic laryngoscopy and computed tomography revealed a round, low-density submucosal mass at right false cord and arytenoepiglottic regions with glottic extension. Microlaryngoscopic biopsy and debulking for this solid tumor were performed without tracheostomy. Schwannoma was confirmed by histopathological study. However, rapidly worsening stridor occurred 2 weeks after the surgery. Fiberoptic laryngoscopy showed an exophytic tumor occupying the right hemilarynx with airway compromise. Definite complete excision of the tumor was performed by right vertical hemilaryngectomy. At 5-month follow-up, the laryngeal wound was clear without signs of recurrence. Rapid occurrence of airway obstruction after debulking and biopsy was demonstrated in this case. Vertical hemilaryngectomy was inevitable to cure this potentially life-threatening laryngeal schwannoma in this young female with postoperative serviceable voice.


Assuntos
Neoplasias Laríngeas/patologia , Pneumopatias Obstrutivas/patologia , Neurilemoma/patologia , Adulto , Feminino , Rouquidão , Humanos , Neoplasias Laríngeas/complicações , Neoplasias Laríngeas/cirurgia , Laringectomia , Pneumopatias Obstrutivas/etiologia , Pneumopatias Obstrutivas/cirurgia , Neurilemoma/complicações , Neurilemoma/cirurgia , Prognóstico , Tomografia Computadorizada por Raios X , Adulto Jovem
6.
ScientificWorldJournal ; 2014: 183548, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25389533

RESUMO

Betel quid (BQ) and areca nut (AN) (major BQ ingredient) are group I human carcinogens illustrated by International Agency for Research on Cancer and are closely associated with an elevated risk of oral potentially malignant disorders (OPMDs) and cancers of the oral cavity and pharynx. The primary alkaloid of AN, arecoline, can be metabolized via the monoamine oxidase (MAO) gene by inducing reactive oxygen species (ROS). The aim of this study was to investigate whether the variants of the susceptible candidate MAO genes are associated with OPMDs and oral and pharyngeal cancer. A significant trend of MAO-A mRNA expression was found in in vitro studies. Using paired human tissues, we confirmed the significantly decreased expression of MAO-A and MAO-B in cancerous tissues when compared with adjacent noncancerous tissues. Moreover, we determined that MAO-A single nucleotide polymorphism variants are significantly linked with oral and pharyngeal cancer patients in comparison to OPMDs patients [rs5953210 risk G-allele, odds ratio = 1.76; 95% confidence interval = 1.02-3.01]. In conclusion, we suggested that susceptible MAO family variants associated with oral and pharyngeal cancer may be implicated in the modulation of MAO gene activity associated with ROS.


Assuntos
Arecolina/toxicidade , Carcinoma de Células Escamosas/genética , Monoaminoxidase/genética , Neoplasias Bucais/genética , Neoplasias Faríngeas/genética , RNA Mensageiro/genética , Areca/química , Arecolina/metabolismo , Carcinoma de Células Escamosas/enzimologia , Carcinoma de Células Escamosas/patologia , Expressão Gênica , Humanos , Monoaminoxidase/metabolismo , Boca/enzimologia , Boca/patologia , Neoplasias Bucais/enzimologia , Neoplasias Bucais/patologia , Neoplasias Faríngeas/enzimologia , Neoplasias Faríngeas/patologia , Faringe/enzimologia , Faringe/patologia , Polimorfismo de Nucleotídeo Único , RNA Mensageiro/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Risco , Microambiente Tumoral
7.
ScientificWorldJournal ; 2014: 810561, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25114974

RESUMO

Betel quid (BQ) is a psychostimulant, an addictive substance, and a group 1 carcinogen that exhibits the potential to induce adverse health effects. Approximately, 600 million users chew a variety of BQ. Areca nut (AN) is a necessary ingredient in BQ products. Arecoline is the primary alkaloid in the AN and can be metabolized through the cytochrome P450 (CYP) superfamily by inducing reactive oxygen species (ROS) production. Full-length CYP26B1 is related to the development of oral pharyngeal cancers. We investigated whether a splice variant of CYP26B1 is associated with the occurrence of ROS related oral and pharyngeal cancer. Cytotoxicity assays were used to measure the effects of arecoline on cell viability in a dose-dependent manner. In vitro and in vivo studies were conducted to evaluate the expression of the CYP26B1 splice variant. The CYP26B1 splice variant exhibited lower expression than did full-length CYP26B1 in the human gingival fibroblast-1 and Ca9-22 cell models. Increased expression of the CYP26B1 splice variant was observed in human oral cancer tissue compared with adjacent normal tissue, and increased expression was observed in patients at a late tumor stage. Our results suggested that the CYP26B1 splice variant is associated with the occurrence of BQ-related oral cancer.


Assuntos
Processamento Alternativo , Sistema Enzimático do Citocromo P-450/genética , Neoplasias Bucais/genética , Areca/química , Arecolina/efeitos adversos , Carcinógenos , Carcinoma de Células Escamosas/induzido quimicamente , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Relação Dose-Resposta a Droga , Expressão Gênica , Humanos , Neoplasias Bucais/induzido quimicamente , Ácido Retinoico 4 Hidroxilase
8.
Int J Cancer ; 131(5): E733-43, 2012 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-22174014

RESUMO

Little is known about any consequences of swallowing tobacco-free betel-quid (TF-BQ) juice/remnants following chewing and its carcinogenic impact on the upper aerodigestive tract (UADT) to gastrointestinal tract (GIT). We investigated the neoplastic impact of TF-BQ on different anatomical locations along UADT and GIT, and differences according to their histological categories. We conducted a multicenter case-control study examining patients with 2,163 pathology-proven UADT and GIT cancers, comparing them with 2,250 control subjects. Generalized additive models, piecewise regression and polytomous logistic models were applied to identify possible dose-dependent structures and cancer risks. Contrary to nonsignificant GIT-adenocarcinoma risk (aOR=0.9), TF-BQ users experienced a 1.7- to 16.2-fold higher risk of UADT-squamous cell carcinomas than nonusers, with the peak risk discovered in oral neoplasms. We separately observed a curvilinear and linear TF-BQ dose-risk relationship in oral/pharyngeal/esophageal and laryngeal cancers. Chewers of betel inflorescence were generally at a greater UADT cancer risk. A higher first-piecewise increased risk of esophageal cancer was recognized among areca-fluid swallowers than among nonswallowers (continuous aOR=1.12 vs. 1.03). TF-BQ use accounted for 66.1-78.7% and 17.8-33.2% of the cases of oral/pharyngeal and esophageal/laryngeal cancers, respectively. However, a reduction from heavy TF-BQ consumption to low-to-moderate consumption only reduced 11.3-34.6% of etiologic fraction of oral/pharyngeal cancers. Alcohol supra-additively modified the risk of TF-BQ in determining the development of oral, pharyngeal and esophageal cancers. In conclusion, the interplay of TF-BQ and alcohol/tobacco use, combined with how chewing habit is practiced, influences carcinogenic consequences on anatomically diverse sites of UADT and GIT cancers, and histologically different types.


Assuntos
Areca/efeitos adversos , Carcinoma de Células Escamosas/patologia , Neoplasias Esofágicas/patologia , Neoplasias Gastrointestinais/patologia , Neoplasias Laríngeas/patologia , Neoplasias Faríngeas/patologia , Adulto , Idoso , Consumo de Bebidas Alcoólicas/efeitos adversos , Carcinógenos/farmacologia , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/etiologia , Estudos de Casos e Controles , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/etiologia , Feminino , Seguimentos , Neoplasias Gastrointestinais/epidemiologia , Neoplasias Gastrointestinais/etiologia , Humanos , Incidência , Neoplasias Laríngeas/epidemiologia , Neoplasias Laríngeas/etiologia , Masculino , Pessoa de Meia-Idade , Neoplasias Faríngeas/epidemiologia , Neoplasias Faríngeas/etiologia , Prognóstico , Fatores de Risco , Fumar/efeitos adversos , Taiwan/epidemiologia
9.
Am J Otolaryngol ; 33(1): 1-5, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-21306793

RESUMO

PURPOSE: The nonrecurrent laryngeal nerve (NRLN) is a rare anatomical variant but associated with high risk of nerve injury during thyroid and parathyroid operations. Therefore, intraoperative detection and verification of NRLN are necessary. METHOD: A total of 390 consecutive patients who underwent thyroid and parathyroid operations (310 RLNs dissected on the right side and 293 nerves on the left side) were enrolled. Electrically evoked electromyography was recorded from the vocalis muscles via an endotracheal tube with glottis surface recording electrodes. At an early stage of operation, vagal nerve was routinely stimulated at the level of inferior thyroid pole to ensure normal path of RLN. If there is a negative response from lower position but positive response from upper vagal stimulation, it indicates the occurrence of a NRLN, and we localize its separation point and path. RESULTS: Four right NRLNs (1.3%) without preoperative recognition were successfully detected at an early stage of operation. Three patients were operated on for thyroid disease, one for parathyroid adenoma and all were associated with right aberrant subclavian artery. All NRLNs were localized and identified precisely with intraoperative neuromonitoring. Functional integrity of all nerves was confirmed by the intraoperative neuromonitoring and postoperative laryngeal examination. CONCLUSIONS: Vagal stimulation at the early stage of operation is a simple, useful, and reliable procedure to detect and identify the NRLN.


Assuntos
Monitorização Intraoperatória/métodos , Doenças das Paratireoides/cirurgia , Nervo Laríngeo Recorrente/anormalidades , Doenças da Glândula Tireoide/cirurgia , Estimulação Elétrica , Eletromiografia , Feminino , Humanos , Intubação Intratraqueal , Masculino , Artéria Subclávia/anormalidades
10.
PLoS One ; 17(2): e0263773, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35167611

RESUMO

BACKGROUND: The survival rate of head and neck squamous cell carcinoma (HNSCC) patients with secondary primary malignancy (SPM) showed no significant improvement for decades, however, the impact of advances in diagnostic tools is rarely mentioned. This study investigated the clinical characteristic of HNSCC with SPM over a 27-year period especially from the perspective of diagnostic tools. METHODS: This study evaluated 157 HNSCC patients with SPM. The patients were divided into two groups according to the time of SPM diagnosis (Group A:1992-2003; Group B: 2004-2014). Age, gender, stage of first primary malignancy (FPM), SPM interval, overall survival, and disease-free survival were compared between groups. RESULTS: Group B had significantly more SPM developed rate (p = 0.002), more SPM patients with advanced stage of FPM (p = 0.001), synchronous SPM (p = 0.006), and shorter SPM interval (p<0.001) compared to Group A. The survival rate in Group B was not significantly better than Group A. CONCLUSION: Among patients diagnosed with HNSCC recently, more SPMs are diagnosed in a shorter time interval and in a more advanced stage. The overall advances in diagnostic tools cannot significantly improve SPM survival, however, it enables more patients to receive corresponding treatment.


Assuntos
Detecção Precoce de Câncer/tendências , Neoplasias de Cabeça e Pescoço/diagnóstico , Segunda Neoplasia Primária/diagnóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico , Idoso , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Segunda Neoplasia Primária/mortalidade , Segunda Neoplasia Primária/patologia , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Análise de Sobrevida
11.
J Oral Pathol Med ; 40(9): 684-92, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21385213

RESUMO

BACKGROUND: Recognition of how risk factors affect the age when cancers are first diagnosed may help to establish more appropriate cancer screening and preventive strategies. METHODS: To investigate the independent and synergistic effects of alcohol, tobacco-free betel-quid (TF-BQ), and cigarette use on diagnosis age and dissemination of upper aerodigestive tract squamous cell carcinoma (UADT-SCC), we recruited pathology-proven 1522 patients with UADT-SCC for study. RESULTS: A 49-, 53-, 57-, and 62-year-old stepwise older median age at carcinoma diagnosis was, respectively, found among patients with oral, pharyngeal, esophageal, and laryngeal cancer. Oral cavity (53.2%) and larynx (11.6%) were separately the dominant and recessive sites where the UADT-SCC occurred. Although alcohol and tobacco bestowed increased risks of earlier tumor occurrence only for oral/pharyngeal and oral cancers, respectively, TF-BQ was consistently observed to confer elevated age-associated risks for each UADT-SCC [adjusted hazard ratio (aHR) = 1.6-2.3]. Alcohol and TF-BQ joint consumers experienced a stepwise increased cumulative risk (CR) of contracting carcinomas of the larynx (46.2%), esophagus (47.5%), pharynx (53.5%), and oral cavity (60.5-71.0%), with >68% of CRs found among drinkers who started chewing before age 20. Alcohol + Betel + Cigarette and Alcohol + Betel users exhibited earlier diagnosis ages than non-users: 10 years ahead for oral cancer, 7, 17, and 12 years earlier for pharyngeal, esophageal, and laryngeal cancers. Noticeably, higher cumulative cancer risks regarding earlier tumor occurrence were correspondingly identified for these users aged 43, 49, 43, and 44 upward. CONCLUSIONS: Tobacco-free betel-quid, in conjunction with alcohol and/or tobacco consumption, impacts early cancer occurrence for specific UADT-SCC and influences tumor site incidence pattern of these neoplasms.


Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Areca/efeitos adversos , Carcinoma de Células Escamosas/etiologia , Neoplasias de Cabeça e Pescoço/etiologia , Fumar/efeitos adversos , Adulto , Fatores Etários , Idoso , Carcinoma de Células Escamosas/diagnóstico , Dieta , Escolaridade , Neoplasias Esofágicas/etiologia , Etnicidade , Neoplasias de Cabeça e Pescoço/diagnóstico , Humanos , Neoplasias Laríngeas/etiologia , Pessoa de Meia-Idade , Neoplasias Bucais/etiologia , Estadiamento de Neoplasias , Neoplasias Faríngeas/etiologia , Fatores de Risco , Fatores Sexuais , Tabaco sem Fumaça/efeitos adversos , Adulto Jovem
12.
J Pers Med ; 11(5)2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-34068585

RESUMO

ATM and BRCA1 are DNA repair genes that play a central role in homologous recombination repair. Alterations of ATM and BRCA1 gene expression are found in cancers, some of which are correlated with treatment response and patient outcome. However, the role of ATM and BRCA1 gene expression in head and neck cancer (HNC) is not well characterized. Here, we examined the prognostic role of ATM and BRCA1 expression in two HNC cohorts with and without betel quid (BQ) exposure. The results showed that the expression of ATM and BRCA1 was downregulated in BQ-associated HNC, as the BQ ingredient arecoline could suppress the expression of both genes. Low expression of either ATM or BRCA1 was correlated with poor overall survival (OS) and was an independent prognostic factor in multivariate analysis (ATM HR: 1.895, p = 0.041; BRCA1 HR: 2.163, p = 0.040). The combination of ATM and BRCA1 expression states further improved on the prediction of OS (HR: 4.195, p = 0.001, both low vs. both high expression). Transcriptomic analysis showed that inhibition of ATM kinase by KU55933 induced apoptosis signaling and potentiated cisplatin-induced cytotoxicity. These data unveil poor prognosis in the HNC patient subgroup with low expression of ATM and BRCA1 and support the notion of ATM-targeted therapy.

13.
Front Endocrinol (Lausanne) ; 12: 788878, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34867830

RESUMO

Objectives: High-pitched voice impairment (HPVI) is not uncommon in patients without recurrent laryngeal nerve (RLN) or external branch of superior laryngeal nerve (EBSLN) injury after thyroidectomy. This study evaluated the correlation between subjective and objective HPVI in patients after thyroid surgery. Methods: This study analyzed 775 patients without preoperative subjective HPVI and underwent neuromonitored thyroidectomy with normal RLN/EBSLN function. Multi-dimensional voice program, voice range profile and Index of voice and swallowing handicap of thyroidectomy (IVST) were performed during the preoperative(I) period and the immediate(II), short-term(III) and long-term(IV) postoperative periods. The severity of objective HPVI was categorized into four groups according to the decrease in maximum frequency (Fmax): <20%, 20-40%, 40-60%, and >60%. Subjective HPVI was evaluated according to the patient's answers on the IVST. Results: As the severity of objective HPVI increased, patients were significantly more to receive bilateral surgery (p=0.002) and have subjective HPVI (p<0.001), and there was no correlation with IVST scores. Among 211(27.2%) patients with subjective HPVI, patients were significantly more to receive bilateral surgery (p=0.003) and central neck dissection(p<0.001). These patients had very similar trends for Fmax, pitch range, and mean fundamental frequency as patients with 20-40% Fmax decrease (p>0.05) and had higher Jitter, Shimmer, and IVST scores than patients in any of the objective HPVI groups; subjective HPVI lasted until period-IV. Conclusion: The factors that affect a patient's subjective HPVI are complex, and voice stability (Jitter and Shimmer) is no less important than the Fmax level. When patients have subjective HPVI without a significant Fmax decrease after thyroid surgery, abnormal voice stability should be considered and managed. Fmax and IVST scores should be interpreted comprehensively, and surgeons and speech-language pathologists should work together to identify patients with HPVI early and arrange speech therapy for them. Regarding the process of fibrosis formation, anti-adhesive material application and postoperative intervention for HPVI require more future research.


Assuntos
Autoavaliação Diagnóstica , Percepção da Altura Sonora , Complicações Pós-Operatórias/diagnóstico , Glândula Tireoide/cirurgia , Tireoidectomia/tendências , Distúrbios da Voz/diagnóstico , Adulto , Idoso , Feminino , Humanos , Nervos Laríngeos/cirurgia , Masculino , Pessoa de Meia-Idade , Monitorização Intraoperatória/métodos , Percepção da Altura Sonora/fisiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/fisiopatologia , Estudos Retrospectivos , Tireoidectomia/efeitos adversos , Distúrbios da Voz/etiologia , Distúrbios da Voz/fisiopatologia
14.
Front Endocrinol (Lausanne) ; 12: 755231, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34917026

RESUMO

Objectives: In patients with recurrent laryngeal nerve (RLN) injury after thyroid surgery, unrecovered vocal fold motion (VFM) and subjective voice impairment cause extreme distress. For surgeons, treating these poor outcomes is extremely challenging. To enable early treatment of VFM impairment, this study evaluated prognostic indicators of non-transection RLN injury and VFM impairment after thyroid surgery and evaluated correlations between intraoperative neuromonitoring (IONM) findings and perioperative voice parameters. Methods: 82 adult patients had postoperative VFM impairment after thyroidectomy were enrolled. Demographic characteristics, RLN electromyography (EMG), and RLN injury mechanism were compared. Multi-dimensional voice program, voice range profile and Index of voice and swallowing handicap of thyroidectomy (IVST) were administered during I-preoperative; II-immediate, III-short-term and IV-long-term postoperative periods. The patients were divided into R/U Group according to the VFM was recovered/unrecovered 3 months after surgery. The patients in U Group were divided into U1/U2 Group according to total IVST score change was <4 and ≥4 during period-IV. Results: Compared to R Group (42 patients), U Group (38 patients) had significantly more patients with EMG >90% decrease in the injured RLN (p<0.001) and thermal injury as the RLN injury mechanism (p=0.002). Voice parameter impairments were more severe in U Group compared to R Group. Compared to U1 group (19 patients), U2 Group (19 patients) had a significantly larger proportion of patients with EMG decrease >90% in the injured RLN (p=0.022) and thermal injury as the RLN injury mechanism (p=0.017). A large pitch range decrease in period-II was a prognostic indicator of a moderate/severe long-term postoperative subjective voice impairment. Conclusion: This study is the first to evaluate correlations between IONM findings and voice outcomes in patients with VFM impairment after thyroid surgery. Thyroid surgeons should make every effort to avoid severe type RLN injury (e.g., thermal injury or injury causing EMG decrease >90%), which raises the risk of unrecovered VFM and moderate/severe long-term postoperative subjective voice impairment. Using objective voice parameters (e.g., pitch range) as prognostic indicators not only enables surgeons to earlier identify patients with low voice satisfaction after surgery, and also enable implementation of interventions sufficiently early to maintain quality of life.


Assuntos
Complicações Pós-Operatórias/fisiopatologia , Traumatismos do Nervo Laríngeo Recorrente/fisiopatologia , Prega Vocal/fisiopatologia , Adulto , Idoso , Feminino , Humanos , Monitorização Neurofisiológica Intraoperatória , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Prognóstico , Traumatismos do Nervo Laríngeo Recorrente/diagnóstico , Traumatismos do Nervo Laríngeo Recorrente/etiologia , Tireoidectomia/efeitos adversos
15.
Cancers (Basel) ; 13(21)2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34771543

RESUMO

Intraoperative neuromonitoring can qualify and quantify RLN function during thyroid surgery. This study investigated how the severity and mechanism of RLN dysfunction during monitored thyroid surgery affected postoperative voice. This retrospective study analyzed 1021 patients that received standardized monitored thyroidectomy. Patients had post-dissection RLN(R2) signal <50%, 50-90% and >90% decrease from pre-dissection RLN(R1) signal were classified into Group A-no/mild, B-moderate, and C-severe RLN dysfunction, respectively. Demographic characteristics, RLN injury mechanisms(mechanical/thermal) and voice analysis parameters were recorded. More patients in the group with higher severity of RLN dysfunction had malignant pathology results (A/B/C = 35%/48%/55%, p = 0.017), received neck dissection (A/B/C = 17%/31%/55%, p < 0.001), had thermal injury (p = 0.006), and had asymmetric vocal fold motion in long-term postoperative periods (A/B/C = 0%/8%/62%, p < 0.001). In postoperative periods, Group C patients had significantly worse voice outcomes in several voice parameters in comparison to Group A/B. Thermal injury was associated with larger voice impairments compared to mechanical injury. This report is the first to discuss the severity and mechanism of RLN dysfunction and postoperative voice in patients who received monitored thyroidectomy. To optimize voice and swallowing outcomes after thyroidectomy, avoiding thermal injury is mandatory, and mechanical injury must be identified early to avoid a more severe dysfunction.

16.
World J Surg ; 34(10): 2383-8, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20512491

RESUMO

OBJECTIVES: The aim of this study was to identify the preoperative factors that affect the survival of patients who undergo esophagogastrectomy after corrosive ingestion, using analysis of their physiological condition, associated diseases, physical examination, and laboratory data. METHODS: Between January 1995 and December 2005, 71 consecutive patients who underwent esophagogastrectomy for corrosive ingestion injuries were retrospectively reviewed. Of them, 41 survived and 30 (42.3%) died during the perioperative period. Logistic regression analyses were used to model markers for postoperative mortality, including descriptive data, clinical symptoms/signs, and laboratory data. RESULTS: There were 35 males and 36 females included in the study, with an average age of 54.7 +/- 14.9 years. After adjustments in the logistic regression model, age of over 65 years (p = 0.021), presence of gross hematuria (p = 0.016), twofold level of serum AST (p = 0.012), blood pH level below 7.2 (p = 0.017), and deficit of blood base over 16 (p = 0.007) were found to be independent risk factors for patient mortality. CONCLUSIONS: We consider age over 65 years, preoperative pH < 7.2, base deficit >16, twofold level of serum AST, and presence of gross hematuria to be the important factors predicting postoperative hospital mortality in patients presenting with corrosive ingestion injuries who require emergency surgery.


Assuntos
Cáusticos/efeitos adversos , Esofagectomia/mortalidade , Gastrectomia/mortalidade , Trato Gastrointestinal/lesões , Trato Gastrointestinal/cirurgia , Mortalidade Hospitalar , Doença Aguda , Adulto , Idoso , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos
17.
World J Surg ; 34(8): 1832-9, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20414775

RESUMO

BACKGROUND: The prognosis and quality of life (QOL) for those with cervical esophageal cancer is extremely poor, and chemoradiotherapy remains the mainstay treatment. During the past few years, our surgical teams has implemented a more aggressive and radical resection: total laryngopharyngectomy with neck dissection, total esophagectomy, and reconstruction with stomach. This study compares the results of chemoradiotherapy and that of the aforementioned surgical approach. METHODS: This is a retrospective study of 15 patients who underwent radical resection and 14 patients who received chemoradiation. Their age, sex, tumor stage and grade, pre- and posttreatment dysphagia scores, operating time, blood loss, length of intensive care and postoperative stay, days to resume oral intake, complications, Eastern Cooperative Oncology Group (ECOG) status, QOL score, and disease-specific survival were recorded and compared. RESULTS: There were no significant differences in age, sex, pretreatment dysphagia score, cancer stage and grade, ECOG status (posttreatment), associate diseases, preoperative QOL, or follow-up period between the two groups. However, the posttreatment dysphagia score was significantly better for the operative group (P < 0.001). QOL improved in both groups, and the operative group seemed better although the difference was not significant. In addition, the survival between the two groups was statistically insignificant (P = 0.97, log-rank test). CONCLUSIONS: Our experience showed that radical surgery that includes total laryngopharyngectomy with neck dissection, total esophagectomy, and reconstruction with stomach for cervical esophageal cancer is beneficial to patients in terms of better eating.


Assuntos
Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/cirurgia , Adulto , Idoso , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/radioterapia , Distribuição de Qui-Quadrado , Terapia Combinada , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/radioterapia , Esofagectomia , Feminino , Humanos , Laringectomia , Masculino , Pessoa de Meia-Idade , Esvaziamento Cervical , Estadiamento de Neoplasias , Complicações Pós-Operatórias , Prognóstico , Qualidade de Vida , Procedimentos de Cirurgia Plástica , Estudos Retrospectivos , Estatísticas não Paramétricas , Estômago/transplante , Toracotomia , Traqueostomia , Resultado do Tratamento
18.
World J Surg ; 34(2): 223-9, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20020124

RESUMO

BACKGROUND: The lack of standardized procedures of intraoperative neuromonitoring (IONM) during thyroid operations may lead to highly variable results, and many of these results can cause misleading information and, conversely, increase the risk of recurrent laryngeal nerve (RLN) injury. Therefore, standardization of IONM procedures is necessary. METHODS: A total of 289 patients (435 nerves at risk) who underwent thyroidectomy by the same surgeon were enrolled in this study. Each patient was intubated with EMG endotracheal tube by the same anesthesiologist. Standardized IONM procedures were applied in each patient. The procedures include preoperative and postoperative video-recording of vocal cord movement, ensuring the correct position of electrodes after the neck was placed at full extension, vagal stimulation and registration of EMG signals before and after RLN dissection, and photographic documentation of the exposed RLN. RESULTS: Five patients encountered dysfunction of IONM, which was caused by malposition of electrodes and the problem was detected at once. One patient with non-RLN was detected at the earlier stage of operation. Eighteen nerves experienced loss of EMG signals during thyroid dissection, and the causes of nerve injuries were well elucidated with the application of our standardized IONM procedures. CONCLUSIONS: The standardized IONM procedures are useful and helpful not only to eliminate false IONM results, but also to elucidate the mechanism of RLN injury. After ascertaining the surgical pitfalls and improving the surgical techniques, the palsy rate was significantly reduced in this study.


Assuntos
Complicações Intraoperatórias/prevenção & controle , Monitorização Intraoperatória/normas , Traumatismos do Nervo Laríngeo Recorrente , Tireoidectomia/efeitos adversos , Paralisia das Pregas Vocais/prevenção & controle , Distribuição de Qui-Quadrado , Eletromiografia , Feminino , Humanos , Doença Iatrogênica/prevenção & controle , Complicações Intraoperatórias/etiologia , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Paralisia das Pregas Vocais/etiologia
19.
Langenbecks Arch Surg ; 395(7): 893-9, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20652584

RESUMO

BACKGROUND: Standardisation of the intraoperative neuromonitoring (IONM) technique is a fundamental aspect in monitored thyroid surgery. Vagal nerve (VN) stimulation is essential for problem solving, recognition of any inferior laryngeal nerve (ILN) lesions and prediction of ILN post-operative function. Issues that have been overlooked in the literature, particularly in terms of prospective approaches, are the topographic relationship of the VN with the carotid and jugular vessels as well as the neurophysiology of the VN and ILN that have been studied, with a prospective approach, in patients with various thyroid diseases. METHODS: Cooperation with the Human Morphology Department resulted in the completion of a dedicated anatomy report, with the clear objective of providing a detailed anatomic and neurophysiologic description of the VN (n = 263). RESULTS: VN identification and stimulation was feasible in all cases and did not result in increased morbidity or operative time. Most VNs lay on the posterior region of the carotid ship (73%), i.e. the P position in accordance with our model. Mean amplitudes of EMG signals obtained from VN stimulation were 750 ± 279 µV, lower than those obtained with direct INL stimulation (1,086 ± 349 µV). CONCLUSION: A better understanding of the variability in the VN may be useful not only to minimise complications but also to guarantee an accurate IONM.


Assuntos
Monitorização Intraoperatória/normas , Nervo Laríngeo Recorrente/anatomia & histologia , Tireoidectomia/métodos , Nervo Vago/anatomia & histologia , Paralisia das Pregas Vocais/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Estimulação Elétrica , Eletromiografia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Intraoperatória/métodos , Neurofisiologia , Nervo Laríngeo Recorrente/fisiologia , Nervo Laríngeo Recorrente/cirurgia , Doenças da Glândula Tireoide/patologia , Doenças da Glândula Tireoide/cirurgia , Resultado do Tratamento , Nervo Vago/fisiologia , Nervo Vago/cirurgia , Estimulação do Nervo Vago/métodos , Adulto Jovem
20.
Cancers (Basel) ; 12(8)2020 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-32722430

RESUMO

Arecoline is the principal alkaloid in the areca nut, a component of betel quids (BQs), which are carcinogenic to humans. Epidemiological studies indicate that BQ-chewing contributes to the occurrence of head and neck cancer (HNC). Previously, we have reported that arecoline (0.3 mM) is able to inhibit DNA repair in a p53-dependent pathway, but the underlying mechanism is unclear. Here we demonstrated that arecoline suppressed the expression of DDB2, which is transcriptionally regulated by p53 and is required for nucleotide excision repair (NER). Ectopic expression of DDB2 restored NER activity in arecoline-treated cells, suggesting that DDB2 downregulation was critical for arecoline-mediated NER inhibition. Mechanistically, arecoline inhibited p53-induced DDB2 promoter activity through the DNA-binding but not the transactivation domain of p53. Both NER and DDB2 promoter activities declined in the chronic arecoline-exposed cells, which were consistent with the downregulated DDB2 mRNA in BQ-associated HNC specimens, but not in those of The Cancer Genome Atlas (TCGA) cohort (no BQ exposure). Lower DDB2 mRNA expression was correlated with a poor outcome in HNC patients. These data uncover one of mechanisms underlying arecoline-mediated carcinogenicity through inhibiting p53-regulated DDB2 expression and DNA repair.

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