Adherence to a shoulder dysfunction physical therapy protocol after neck dissection with accessory nerve preservation in head-and-neck cancer patients: An uncontrolled clinical trial.

Objective: Accessory nerve (AN) manipulation or resection during neck dissection (ND) generates accessory nerve shoulder dysfunction (ANSD). The aim of the present study was to assess adherence to a supervised physiotherapy protocol and subsequent changes in the functionality scores of patients with ASND with accessory nerve (AN) preservation. Methods: This study consisted of an uncontrolled clinical trial was carried out at the Department of Head and Neck Surgery and Otorhinolaryngology at the A.C. Camargo Cancer Center, comprising progressive isotonic and isometric strengthening of scapular stabilizer muscles. In patients with head-and-neck cancer underwent ND with AN preservation and patients with ANSD. Shoulder range of motion (ROM), middle trapezius, lower trapezius, rhomboid and anterior serratus muscle strength, pain, and quality of life (QoL) were measured in the pre-operative and 1st and 3rd post-operative months. There were included patients over 18 years old, with head-and-neck cancer who underwent ND with AN preservation and patients with ANSD. Results: A total of 55 patients were evaluated, with a mean age of 53 (±13.23). Significant improvement in the functionality scores of almost all variables between pre- and post- physiotherapy was observed. Most patients (70.9%) adhered and completed the protocol, obtaining significantly greater ROM abduction (P = 0.009) and lower trapezius strength (P = 0.011) than partially performing patients. Conclusion: When performed completely, the proposed physiotherapy protocol can minimize loss in muscle movements and strength, especially limited after ND. The results indicate that the proposed protocol is safe and has the potential to reduce ANSD.

De-escalation studies in HPV-positive oropharyngeal cancer: How should we proceed?

Human papilloma virus (HPV) is a well-established causative factor in a subset of squamous cell carcinomas of the head and neck (HNSCC). Although HPV can be detected in various anatomical subsites, HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) is the most common HPV-related malignancy of the head and neck, and its worldwide incidence is constantly rising. Patients with OPSCC are generally younger, have less co-morbidities and generally have better prognosis due to different biological mechanisms of carcinogenesis. These facts have generated hypotheses on potential treatment modifications, aiming to minimize treatment-related toxicities without compromising therapy efficacy. Numerous randomized clinical trials have been designed to verify this strategy and increasingly real-world evidence data from retrospective, observational studies is becoming available. Until now, the data do not support any modification in contemporary treatment protocols. In this narrative review, we outline recent data provided by both randomized controlled trials and real-world evidence of HPV-positive OPSCC in terms of clinical value. We critically analyze the potential value and drawbacks of the available data and highlight future research directions. This article was written by members and invitees of the International Head and Neck Scientific Group.(www.IHNSG.com).

Validação para a língua portuguesa do Gothenburg Trismus Questionnaire (GTQ) / Validation of the Portuguese version of the Gothenburg Trismus Questionnaire

Atualmente, o Gothenburg Trismus Questionnaire (GTQ) é o único questionário de qualidade de vida específico sobre trismo. A afecção, definida como restrição à abertura da boca, gera prejuízo a atividades habituais como comer, engolir, falar e fazer a higiene oral, trazendo grande desconforto aos pacientes. A tradução de questionários de qualidade de vida desempenha um importante papel no conhecimento da saúde das populações nos diferentes países. O objetivo do presente estudo é apresentar a validação do GTQ para a língua portuguesa, a fim de permitir sua aplicação efetiva nas populações de idioma português. O GTQ foi validado com sucesso para a língua portuguesa conforme os seguintes passos: Tradução, Retradução (back translation), Adaptação cultural e Revalidação.

Currently, the Gothenburg Trismus Questionnaire (GTQ) is the only quality-of-life questionnaire specific for the assessment of trismus. The disease, characterized by limited mouth opening, impairs usual activities such as eating, swallowing, talking, and performing oral hygiene, causing great discomfort to patients. Translation of quality-of-life questionnaires plays an important role in promoting health awareness in the populations of different countries. This study aimed to validate the Portuguese version of the GTQ to allow its effective application in Portuguesespeaking populations. The Portuguese version of the GTQ was successfully validated through the following steps: translation, back translation, cultural adaptation, and revalidation.

Diffusion-Weighted MRI in the Assessment of Early Treatment Response in Patients with Squamous-Cell Carcinoma of the Head and Neck: Comparison with Morphological and PET/CT Findings.

OBJECTIVE: To evaluate changes in apparent diffusion coefficients (ADC) as measured by magnetic resonance imaging (MRI) before and after the treatment of primary tumors and cervical metastases in patients with squamous-cell carcinoma (SCC) of the head and neck, and to compare these values to the results of widely used morphological criteria and [18F]-FDG PET/CT findings. MATERIAL AND METHOD: This was a longitudinal, prospective, single-center nonrandomized trial involving patients with head and neck SCC treated with chemotherapy alone or in combination with radiotherapy. Imaging examinations ([18F]-FDG PET/CT and diffusion-weighted MRI) were performed on the same day, up to one day prior to the beginning of the first treatment cycle, and on the 14th day of the first chemotherapy cycle. Treatment response was evaluated based on the Response Evaluation Criteria in Solid Tumors (RECIST) and World Health Organization (WHO) morphological criteria, as well as PET Response Criteria in Solid Tumors (PERCIST) metabolic criteria. RESULTS: Seventy-five lesions were examined in 23 patients. Pre- and post-treatment comparisons of data pertaining to all target lesions revealed reductions in tumor size and SUV, as well as increases in ADC values, all of which were statistically significant. The increase in ADC following treatment was significantly higher in patients classified as complete responders by both morphological criteria than that observed in any of the other patient groups of response. Patients with a complete metabolic response also showed greater increases in ADC values as compared to the remaining groups. CONCLUSION: The assessment of tumor response based on diffusion-weighted MRI showed an increase in the ADC of cervical lesions following treatment, which was corroborated by morphological and metabolic findings. Associations between changes in ADC values and treatment response categories using morphologic criteria and [18F]-FDG PET/CT were only identified in complete responders.

Induction chemotherapy prior to surgery with or without postoperative radiotherapy for oral cavity cancer patients: Systematic review and meta-analysis.

BACKGROUND: Locoregionally advanced oral cavity cancers are aggressive tumours with high risk of relapse after definitive treatment. This study was performed to assess the effectiveness and safety of induction chemotherapy prior to surgery for untreated oral cavity cancer patients. MATERIAL AND METHODS: Only prospective phase III randomised studies comparing induction chemotherapy followed by surgery with or without postoperative radiotherapy (Chemo Group) compared with surgery with or without postoperative radiotherapy (Control Group) were eligible. Two of the authors independently selected and assessed the studies regarding eligibility criteria and risk of bias. RESULTS: Two studies were selected. A total of 451 patients were randomly assigned to Chemo Group (n=226) versus Control Group (n=225). Most patients had tumours at clinical stages III/IV (89.1%). Both trials were classified as having low risk of bias. No significant overall benefit in favour of induction chemotherapy was found regarding loco-regional recurrence, disease-free survival and overall survival. A subgroup analysis of individual data from cN2 patients showed statistically significant overall survival benefit in favour of induction chemotherapy. The included studies did not directly compare toxicity between the groups and no statistical analysis was performed regarding safety outcomes. CONCLUSIONS: Based on the available studies, induction chemotherapy when administered before surgery with curative intent did not improve clinical outcomes in locoregionally advanced oral cavity cancer patients. Clinically assessed N2 patients might benefit from induction chemotherapy.

Overexpression of HOXB7 homeobox gene in oral cancer induces cellular proliferation and is associated with poor prognosis.

A growing body of evidence has confirmed the involvement of dysregulated expression of HOX genes in cancer. HOX genes are a family of 39 transcription factors, divided in 4 clusters (HOXA to HOXD), that during normal development regulate cell proliferation and specific cell fate. In the present study it was investigated whether genes of the HOXB cluster play a role in oral cancer. We showed that most of the genes in the HOXB network are inactive in oral tissues, with exception of HOXB2, HOXB7 and HOXB13. Expression of HOXB7 was significantly higher in oral squamous cell carcinomas (OSCC) compared to normal oral mucosas. We further demonstrated that HOXB7 overexpression in HaCAT human epithelial cell line promoted proliferation, whereas downregulation of HOXB7 endogenous levels in human oral carcinoma cells (SCC9 cells) decreased proliferation. In OSCCs, expression of HOXB7 and Ki67, a marker of proliferation, correlate strongly with each other (rs=0.79, p<0.006). High immunohistochemical expression of HOXB7 was correlated with T stage (p=0.06), N stage (p=0.07), disease stage (p=0.09) and Ki67 expression (p=0.01), and patients with tumors showing high number of HOXB7-positive cells had shorter overall survival (p=0.08) and shorter disease-free survival after treatment (p=0.10) compared with patients with tumors exhibiting low amount of HOXB7-positive cells. Our data suggest that HOXB7 may contribute to oral carcinogenesis by increasing tumor cell proliferation, and imply that HOXB7 may be an important determinant of OSCC patient prognosis.

Presence of myofibroblasts and expression of matrix metalloproteinase-2 (MMP-2) in ameloblastomas correlate with rupture of the osseous cortical.

Myofibroblasts are frequent in the stroma of neoplasm and by the expression of proteinases they can influence tumor infiltration and progression. In the present study, presence of myofibroblasts and expression of matrix metalloproteinase-2 (MMP-2) and urokinase plasminogen activator (uPA) were examined in intra-osseous solid multicystic ameloblastomas to determine their roles in the clinicopathological features of the tumors. Fifty seven ameloblastomas were analyzed immunohistochemically with antibodies against the isoform alpha of the smooth muscle actin (alpha-SMA), a specific marker of myofibroblasts, MMP-2 and uPA. Myofibroblasts were found in the stroma, in close contact with neoplastic cell islands, of approximately 58% (n = 33) of the ameloblastomas. MMP-2 and uPA were found in the cytoplasm of both neoplastic and stromal cells. A significant correlation between presence of myofibroblasts and MMP-2 expression was observed. Abundant presence of myofibroblast in the stroma of the tumors and expression of MMP-2 in the neoplastic or stromal cells were significantly correlated with rupture of the osseous cortical, which has been considered an important prognostic marker of ameloblastoma aggressiveness. Ours results suggest that abundant presence of myofibroblasts and expression of MMP-2 in solid ameloblastomas may be associated with a more aggressive infiltrative behavior.

E-cadherin abnormalities resulting from CPG methylation promoter in metastatic and nonmetastatic oral cancer.

BACKGROUND: This study aims to compare the alterations in the methylation profiles of E-cadherin in oral cancer, especially in tumors with lowest metatastic potential. METHODS: Nine oral verrucous carcinomas (VCs), 20 oral well-differentiated squamous cell carcinomas without lymph node involvement (SCC-pN0), and 17 with lymph node involvement (SCC-pN+) were analyzed using methylation-specific polymerase chain reaction and immunohistochemical expression of E-cadherin gene. RESULTS: The immunohistochemical expression of E-cadherin in VC was significantly higher (p = .016) when compared with SCC-pN0 and SCC-pN+ groups. The E-cadherin gene methylation was not correlated with its abnormal immunohistochemical expression in VC and SCC-pN0. All tumors of the SCC-pN+ group with unmethylated E-cadherin gene showed significant loss of E-cadherin immunoexpression (p = .044). CONCLUSIONS: The E-cadherin gene methylation presence in tumors with lowest invasive and metastatic potential, such as VC, suggests the early involvement of this epigenetic event in the multistep progression of the oral carcinogenesis.

Mutual paracrine effects of oral squamous cell carcinoma cells and normal oral fibroblasts: induction of fibroblast to myofibroblast transdifferentiation and modulation of tumor cell proliferation.

Several lines of evidence demonstrated that the stroma surrounding the tumors plays an important role in the growth and progression of several neoplasms, including oral squamous cell carcinomas (OSCC). We evaluated the presence of myofibroblasts in OSCC and determined whether their presence is associated with clinicopathological features of the tumors. We also investigated the mutual paracrine effects of tumor cells and myofibroblasts on fibroblast-myofibroblast transdifferentiation and tumor cell proliferation. Immunohistochemical analysis showed the approximately 60% of the OSCCs contained myofibroblasts in the stroma of the tumor. Abundant presence of myofibroblasts significantly correlated with N stage, disease stage, regional recurrence, and proliferative potential of the tumor cells. Using OSCC cell lines and primary oral normal fibroblasts (ONF), we demonstrated that tumor cells induced transdifferentiation of ONFs to myofibroblasts via secretion of transforming growth factor-beta 1 (TGF-beta 1). In turn, myofibroblasts secreted factors that stimulated OSCC cell proliferation, as revealed by measuring BrdU incorporation and Ki67 expression. The results of the study suggest that during tumor invasion OSCC-derived TGF-beta 1 promote fibroblast-myofibroblast transdifferentiation, and that tumor cellular proliferation can be induced by factors released from myofibroblasts, which may favor tumor growth.

[Occupational risks for laryngeal cancer: a case-control study]. / Riscos ocupacionais para o câncer de laringe: um estudo caso-controle.

The most solidly established risk factors for laryngeal cancer are tobacco and alcohol. As for occupational factors, the only established carcinogen is exposure to strong inorganic acid mists. However, asbestos, pesticides, paints, gasoline, diesel engine emissions, dusts, and other factors have been reported in the literature as occupational agents that increase the risk of laryngeal cancer. A hospital-based case-control study was conducted to investigate occupational risk factors for laryngeal cancer. Detailed data on smoking, alcohol consumption, and occupational history were collected for 122 laryngeal cancers and 187 controls matched by frequency (according to sex and age). Laryngeal cancer was associated with exposure to respirable free crystalline silica (OR = 1.83; 95%CI: 1.00-3.36), soot (from coal, coke, fuel oil, or wood) (odds ratio - OR = 1.78; 95% confidence interval - 95%CI: 1.03-3.03), fumes (OR = 2.55; 95%CI: 1.14-5.67), and live animals (OR = 1.80; 95%CI: 1.02-3.19).

Riscos ocupacionais para o câncer de laringe: um estudo caso-controle / Occupational risks for laryngeal cancer: a case-control study

O tabagismo e o consumo de álcool são os fatores de risco mais bem estabelecidos para o câncer de laringe. Com relação aos fatores ocupacionais, o único carcinógeno estabelecido é a exposição a névoas de ácidos inorgânicos fortes. Entretanto, asbesto, pesticidas, tintas, gases de combustão de gasolina e diesel e poeiras, entre outros, aparecem na literatura como agentes ocupacionais que aumentam o risco de câncer de laringe. Um estudo caso-controle de base hospitalar foi conduzido para investigar fatores de risco ocupacionais para câncer de laringe. Foram coletadas informações detalhadas sobre tabagismo, consumo de álcool e história ocupacional de 122 casos de câncer de laringe e 187 controles pareados por freqüência (segundo sexo e idade). Encontrou-se risco aumentado de câncer de laringe nos indivíduos com exposição à sílica cristalina livre respirável (OR = 1,83; IC95 por cento: 1,00-3,36), à fuligem (de carvão mineral, coque, madeira, óleo combustível) (OR = 1,78; IC95 por cento: 1,03-3,03), a fumos em geral (OR = 2,55; IC95 por cento: 1,14-5,67) e a animais vivos (OR = 1,80; IC95 por cento: 1,02-3,19).

The most solidly established risk factors for laryngeal cancer are tobacco and alcohol. As for occupational factors, the only established carcinogen is exposure to strong inorganic acid mists. However, asbestos, pesticides, paints, gasoline, diesel engine emissions, dusts, and other factors have been reported in the literature as occupational agents that increase the risk of laryngeal cancer. A hospital-based case-control study was conducted to investigate occupational risk factors for laryngeal cancer. Detailed data on smoking, alcohol consumption, and occupational history were collected for 122 laryngeal cancers and 187 controls matched by frequency (according to sex and age). Laryngeal cancer was associated with exposure to respirable free crystalline silica (OR = 1.83; 95 percentCI: 1.00-3.36), soot (from coal, coke, fuel oil, or wood) (odds ratio - OR = 1.78; 95 percent confidence interval - 95 percentCI: 1.03-3.03), fumes (OR = 2.55; 95 percentCI: 1.14-5.67), and live animals (OR = 1.80; 95 percentCI: 1.02-3.19).

Intratumor injections of cisplatin and laser thermal therapy for palliative treatment of recurrent cancer.

OBJECTIVE: The aim of this work was to report initial findings on the clinical application of intratumor injection of cisplatin in a gel (CDDP/gel) combined with laser-induced thermal therapy (LITT) for cancer treatment in a single patient with advanced stage disease. BACKGROUND DATA: LITT with the neodymium:yttriumaluminum- garnet (Nd:YAG) laser via fiberoptics is a precise, minimally invasive alternative for thermoablation of unresectable or recurrent head and neck neoplasms, but recurrence is often seen at the treatment margins. Combining intratumor chemotherapy with interstitial laser should be most effective using drugs with thermally enhanced toxicity, such as cisplatin. The CDDP/gel therapeutic implant was expected to retain a higher concentration of cisplatin in the tumor margins for improved LITT treatment of the patient presented. METHODS: In this case report, the cisplatin dose was 0.25 mL gel/cm(3) tumor volume (20 mg of CDDP) followed by LITT (Nd:YAG laser, 50 W, PD = 2,200 J/cm(2)) after the chemotherapy session. RESULTS: The patient responded with local tumor eradication, and no signs of systemic toxicity were observed related to this therapy. However, the patient developed progressive metastatic disease in the lungs and died 2.5 months later. CONCLUSIONS: This is a report of a patient with an accessible solid tumor who was treated with intratumor injection of CDDP/gel followed by LITT, which proved to be feasible. Based on preclinical evidence obtained at UCLA and the results of this study, we are encouraged to continue our refinement of LITT combined with chemotherapy for cancer treatment.

Cytogenetic damage in circulating lymphocytes and buccal mucosa cells of head-and-neck cancer patients undergoing radiotherapy.

This study evaluated cytogenetic damage by measuring the frequency of micronucleated cells (MNC) in peripheral blood and buccal mucosa of head-and-neck cancer patients undergoing radiotherapy. MNC frequencies were assessed in 31 patients before, during, and after radiotherapy, and in 17 healthy controls matched for gender, age, and smoking habits. Results showed no statistically significant difference between patients and controls prior to radiotherapy in cytokinesis-blocked lymphocytes or buccal mucosa cells. During treatment, increased MNC frequencies were observed in both cell types. Micronucleated lymphocyte levels remained high in samples collected 30 to 140 days after the end of treatment, while MNC frequency in buccal mucosa decreased to values statistically similar to baseline values. There is controversy over the effects of age, smoking habit, tumor stage, and/or metastasis on MNC frequency. However, increased frequency of micronucleated buccal mucosa cells was seen in patients under 60 years old and in those with tumors >4 cm. In conclusion, the data show that radiotherapy has a potent clastogenic effect in circulating lymphocytes and buccal mucosa cells of head-and-neck cancer patients, and that the baseline MNC frequency in these two tissues is not a sensitive marker for head-and neck neoplasm.

DNA gains at 8q23.2: a potential early marker in head and neck carcinomas.

Gains or amplifications involving chromosome arm 8q are one of the most recurrent chromosomal alterations in head and neck tumors. To characterize previously reported gains, we performed fluorescence in situ hybridization (FISH) using the sequences BAC RP1179E1 and 8-centromere PMJ 128 as probes. Gains and/or amplifications were detected in all 19 cases evaluated by FISH. The FISH analysis, but not G-banding, revealed homogeneously staining region in three cases. We conclude that gains of one or more genes on chromosome arm 8q may be important for the early stages of head and neck carcinomas.

Differential expression of c-jun and c-fos mRNAs in squamous cell carcinoma of the head and neck: associations with uPA, gelatinase B, and matrilysin mRNAs.

BACKGROUND: Head and neck squamous cell carcinomas (HNSCC) are known for their invasive behavior. The invasiveness of these tumors requires proteases, some of which as urokinase-type plasminogen activator (uPA), gelatinase B and matrilysin are regulated through AP-1 dependent transcriptional mechanisms. AP-1 consists of several proteins, including those encoded by the proto-oncogenes c-jun and c-fos. The aim of this study was to: first, evaluate the expression levels of matrix metalloproteases (matrilysin and gelatinase B) and uPA mRNAs; second, examine whether these genes might be associated with c-jun and c-fos expression; third, examine the relationship between the expression of these genes and HNSCC clinico-pathological features. METHODS: We have analyzed 38 HNSCC primary tumors and matched mucosa tissues for uPA, gelatinase B, matrilysin, c-fos, and c-jun by Northern-blot analysis. RESULTS: uPA, gelatinase B, matrilysin, and c-jun mean levels were statistically higher in the tumors than in the normal adjacent mucosa, whereas no difference was found when c-fos mRNA values were compared, c-jun mRNA expression correlated directly with gelatinase B and matrilysin mRNA levels, but no association with uPA mRNA was observed, c-fos mRNA levels were not associated with the tested proteases, but low levels were determined in tumors from older patients who subsequently developed a 2(nd) tumor. No evidence of correlation between expression of uPA, matrilysin, and c-jun in tumors and clinico-pathological features was found. Gelatinase B mRNA high levels were associated to presence of cervical recurrences. CONCLUSION: Expression of c-jun seems to be involved in the regulation of gelatinase B and matrilysin being not related to uPA. Lack of association with c-fos may indicate that other fos family members might play a role in the transcriptional activity of the analyzed proteases in HNSCC tumors.

Matrix metalloproteinase-2 and -9 activities correlate with the disease-free survival of oral squamous cell carcinoma patients.

The aim of the present study was to determine whether matrix metalloproteinase (MMP) activities are associated with the clinicopathological features of oral squamous cell carcinomas (OSCCs). Forty-four samples of primary OSCCs were microdissected, incubated in serum-free cell culture medium for 16 h, and the activity of secreted MMPs analyzed by gelatin zymography and densitometry. Two major enzymes with gelatinolytic activity were produced by all tumor samples and characterized as MMP-2 and -9 by their molecular weight, immunoprecipitation using monoclonal antibodies, and specific inhibition by 1,10-phenanthroline or EDTA. Patients with tumors showing elevated activity of MMP-2 and -9 had shorter disease-free survival after treatment than patients with tumors exhibiting low MMP activities. These results suggest that the zymographic measurement of the MMP-2 and -9 activities in OSCC specimens may be useful to predict the disease-free survival period of patients affected by these tumors.

Carcinomas múltiplos metacrônicos do conduto auditivo externo e orelha média / Metachronous multiple carcinomas of the external auditory canal and middle ear

Apresentaçao de um caso raro de concorrência múltipla em períodos isolados de carcinoma espinocelular em conduto auditivo externo e orelha média. Destaca-se a importância do tratamento cirúrgico na sobrevida dos pacientes.

Mucormicose rinocerebral: estudo de um caso / Rhinocerebral mucormycosis: report of one case

A mucormicose é uma infecçao fungica rara, geralmente fatal, que acomete pacientes imunodeprimidos como os diabeticos, comumente em cetoacidose ou osportadores de neoplasias malignas, sendo mais frequente as de linhagem hematologica. Dentre as varias formas descritas, a rinocerebral apresenta maior incidencia, sendo sua porta de entrada as vias aereas superiores. O caso apresentado ilustra a gravidade dadoença e a necessidade de seu diagnostico precoce, com consequente instituiçao imediata da terapeutica, que consiste na combinaçao de Anfotericina B e cirurgia, atraves de debridamento amplodo tecido necrotico. Sao comentadas, também, formas alternadas de tratamento