Interferon-gamma and interleukin-10 production by mononuclear cells from patients with advanced head and neck cancer.

OBJECTIVE: This study aims to evaluate the production of interferon-gamma and interleukin-10 by stimulated peripheral blood mononuclear cells isolated from patients with supraglottic laryngeal cancer before and after surgical treatment. METHODS: Fourteen patients with advanced supraglottic laryngeal cancer were studied. Cultures of peripheral blood mononuclear cells isolated during the preoperative and late postoperative periods were stimulated with concanavalin A and Bacille Calmette-Guerin, and the supernatant concentrations of interferon-gamma and interleukin-10 were measured. RESULTS: For non-stimulated cultures, the interferon-gamma levels produced by the preoperative period and the late postoperative period cultures were lower than the levels produced by the control group cultures. The interferon-gamma levels after stimulation with concanavalin A were higher in the late postoperative period cultures than in the preoperative evaluation cultures. Stimulation with Bacille Calmette-Guerin led to the production of similar levels of interferon-gamma and interleukin-10 by all cultures; thus, stimulation increased the levels of interferon-gamma produced by both the preoperative and postoperative cultures relative to the levels produced by the corresponding unstimulated cultures. CONCLUSION: Patients with advanced supraglottic laryngeal cancer exhibit an in vitro deficiency in interferongamma secretion by mononuclear cells. Stimulated cells seem to recover this function during the postoperative period.

Interferon-gamma and interleukin-10 production by mononuclear cells from patients with advanced head and neck cancer

OBJECTIVE: This study aims to evaluate the production of interferon-gamma and interleukin-10 by stimulated peripheral blood mononuclear cells isolated from patients with supraglottic laryngeal cancer before and after surgical treatment. METHODS: Fourteen patients with advanced supraglottic laryngeal cancer were studied. Cultures of peripheral blood mononuclear cells isolated during the preoperative and late postoperative periods were stimulated with concanavalin A and Bacille Calmette-Guerin, and the supernatant concentrations of interferon-gamma and interleukin-10 were measured. RESULTS: For non-stimulated cultures, the interferon-gamma levels produced by the preoperative period and the late postoperative period cultures were lower than the levels produced by the control group cultures. The interferon-gamma levels after stimulation with concanavalin A were higher in the late postoperative period cultures than in the preoperative evaluation cultures. Stimulation with Bacille Calmette-Guerin led to the production of similar levels of interferon-gamma and interleukin-10 by all cultures; thus, stimulation increased the levels of interferon-gamma produced by both the preoperative and postoperative cultures relative to the levels produced by the corresponding unstimulated cultures. CONCLUSION: Patients with advanced supraglottic laryngeal cancer exhibit an in vitro deficiency in interferongamma secretion by mononuclear cells. Stimulated cells seem to recover this function during the postoperative period.

High expression of cancer testis antigens MAGE-A, MAGE-C1/CT7, MAGE-C2/CT10, NY-ESO-1, and gage in advanced squamous cell carcinoma of the larynx.

BACKGROUND: Despite diagnostic and therapeutic advances in head and neck cancer, the 5-year survival of patients with laryngeal cancer has not improved in the last 30 years. Several recent studies indicate that specific targets for immunotherapeutic approaches can be useful in the control of cancer. There is considerable interest in the expression of cancer testis antigens in human cancers since they may serve as the basis for an immunologic approach to therapy. METHODS: We evaluated by immunohistochemical analysis the expression of cancer testis antigens MAGE-A4 (57B), MAGE-C1 (CT7-33), MAGE-A1 (MA454), MAGE-A3 (M3H67), MAGE-C2 (CT10.5), NY-ESO-1 (E978), and GAGE (GAGE) in squamous cell carcinoma (SCC) of the larynx. RESULTS: A total of 63 cases (57 men and 6 women) of laryngeal SCC were available for this study. The findings were correlated with the clinical course and laboratory data. Expression of at least 1 cancer testis antigen was detected in 42 of 63 of the laryngeal SCCs (67%). In 34 of 42 of the positive cases (81%) there was simultaneous expression of ≥2 cancer testis antigens. There was significant correlation between antigen expression and advanced tumor stage (stage III/IV) in cases with reactivity to only 1 antibody (p = .01) as well as in the cases with reactivity to ≥2 primary antibodies (≥2 mAbs, p = .04). There was no association between survival and expression of any of the analyzed antigens. CONCLUSIONS: We find a high incidence of cancer testis antigen expression in SCCs of the larynx, which was correlated with advanced clinical stage. Our data indicate that cancer testis antigens could be valuable vaccine targets in laryngeal tumors, especially in those with a worse prognosis.

Reconstruction of two mandible defects with one fibular flap.

The present report describes an original surgical procedure for the mandibular reconstruction of 2 different defects using a single fibular flap. In addition to the habitual osteotomies, we resected a bone fragment from the middle portion of the flap, with care taken to maintain the integrity of the pedicle throughout its extension to guarantee an adequate blood supply also for the distal portion of the bone flap used for the treatment of the smaller mandibular defect. This simple maneuver permitted the reconstruction of 2 mandibular regions with well-vascularized bone tissue using a single microsurgical flap.

Behavior of the cricopharyngeal segment during esophageal phonation in laryngectomized patients.

BACKGROUND: After total laryngectomy, the interruption of the upper digestive tube and the section of the cricopharyngeal segment alter the high-pressure zone of the pharyngoesophageal transition, which will not only start to have a digestive function, but also be stimulated to take on the production of voice and speech. The pressure observed in the cricopharyngeal segment seems to act as a critical factor for the development of esophageal sound production, and manometry is the procedure capable of quantifying the pressure observed in this region. OBJECTIVE: The objective of the current study was to assess the upper esophageal sphincter pressure in laryngectomized patients who are either successful or unsuccessful esophageal speakers, both at rest and during esophageal phonation, using manometry. METHODS: Twenty laryngectomized persons aged 32 to 83 years (mean, 44.2 years) were submitted to evaluation by a speech pathologist and divided into two groups, ie, successful esophageal speakers (N=12) and unsuccessful esophageal speakers (N=8), according to a scale validated by Wepman et al (1953). The upper esophageal sphincter (UES) pressure was assessed by manometry both at rest and during the following voice emissions in Portuguese: the vowel "a," the monosyllable "pa," and the sentence "papai papou pipoca." The amplitude, the duration of the pressure wave, and the area under the curve were measured. RESULTS: At rest, the mean UES pressure was 11.83 mm Hg for successful esophageal speakers and 9.92 mm Hg for unsuccessful esophageal speakers, with no significant difference between groups; the mean for the two groups as a whole was 11.06 mm Hg. During the voice and speech sequence tests, no significant difference was observed when the emissions in Portuguese of "a," "pa," and the sentence were analyzed separately. CONCLUSION: As the pressure observed at rest did not differ between the successful esophageal speakers and the unsuccessful esophageal speakers, and the amplitude, the duration of the pressure wave, and the area under the amplitude x duration curve were also equal for both groups, we conclude that the cricopharyngeal segment pressure is not a preponderant factor for the acquisition of esophageal voice and speech.

Systemic and local characterization of regulatory T cells in a chronic fungal infection in humans.

The long-term persistence of pathogens in a host is a hallmark of certain infectious diseases, including schistosomiasis, leishmaniasis, and paracoccidioidomycosis (PCM). Natural regulatory T (Treg) cells are involved in control of the immune responses, including response to pathogens. Because CTLA-4 is constitutively expressed in Treg cells and it acts as a negative regulator of T cell activation in patients with PCM, here we investigated the involvement of Treg cells in the control of systemic and local immune response in patients with PCM. We found that the leukocyte subsets were similar in patients and controls, except for CD11c+CD1a+ cells. However, a higher frequency of CD4+CD25+ T cells expressing CTLA-4, glucorticoid-inducible TNFR, membrane-bound TGF-beta, and forkhead-box 3 were observed in PBMC of patients. In accordance, these cells exhibited stronger suppressive activity when compared with those from controls (94.0 vs 67.5% of inhibition of allogeneic T cell proliferation). In addition, the data showed that CD4+CD25+ T cells expressing CTLA-4+, glucocorticoid-inducible TNFR positive, CD103+, CD45RO+, membrane-bound TGF-beta, forkhead-box 3 positive, and the chemokines receptors CCR4 and CCR5 accumulate in the Paracoccidioides brasiliensis-induced lesions. Indeed, the secreted CCL17 and CCL22, both associated with the migration of Treg cells to peripheral tissues, were also detected in the biopsies. Moreover, the CD4+CD25+ T cell derived from lesions, most of them TGF-beta+, also exhibited functional activity in vitro. Altogether, these data provide the first evidence that Treg cells play a role in controlling local and systemic immune response in patients with a fungal-induced granulomatous disease advancing our understanding about the immune regulation in human chronic diseases.

Expression of cancer testis antigens in head and neck squamous cell carcinomas.

BACKGROUND: There is considerable interest in the expression of cancer testis (CT) antigens in human cancers, because they may serve as the basis for diagnostic tests or an immunologic approach to therapy, or as prognostic markers. METHODS: On this basis, we evaluated by semiquantitative reverse-transcriptase polymerase chain reaction (RT-PCR) the expression of genes that code for tumor antigens (melanoma antigen-1 [MAGE-1], MAGE-4, MAGE-10, MAGE-12, B melanoma antigen, CTL-recognized antigen melanoma antigen (CT antigen 2) [LAGE], New York esophageal squamous cell carcinoma antigen (CT antigen 1) [NYESO-1], and preferentially expressed antigen of melanoma [PRAME]) in surgical samples of the tumors, margins, and lymph nodes (when present) from patients with a diagnosis of head and neck carcinoma. The study was conducted on 33 patients (31 men and two women), aged 31 to 94 years (mean, 56 years), with squamous cell carcinomas located in the mouth (15 cases), larynx (14 cases), and pharynx (four cases). RESULTS: The findings were compared with the clinical course and laboratory data. Expression of at least one antigen was observed in 66.6% of cases, with different rates of expression according to tumor staging (100% of T4, 57% of T3, 50% of T1 and T2) and smoking habit. There was a significantly higher expression of multiple genes (two or more) in tumors in advanced stages. CONCLUSIONS: We conclude that the tumor-specific antigen genes are expressed in variable frequencies and intensities in the primary lesions of head and neck squamous cell carcinomas and in their metastases, with expression of the PRAME gene being always present in the metastastatic lymph nodes. In primary lesions, gene expression correlated with smoking habit and with advanced tumors with a higher malignant potential, with the frequent expression of two or more of these genes.

Análise funcional da laringe pós-cordectomia, reconstruída com retalho de prega vestibular / Functional analysis of the larynx reconstructed with vestibular fold flap after cordectomy

Várias técnicas para a reconstrução da laringe, pós laringectomias parciais verticais, são citadas na literatura, algumas utilizando estruturas da própria laringe, como a prega vestibular, porém, poucas dão destaque à análise das funções laríngeas após estas reconstruções. Este estudo teve como objetivo avaliar as funções laríngeas em pacientes submetidos à cordectomia completa (tipo IV), reconstruídos com retalho de prega vestibular. FORMA DE ESTUDO: Estudo de coorte transversal. MATERIAL E MÉTODO: Dez pacientes, nove do sexo masculino e um do sexo feminino, com idades entre 45 e 75 anos, e média de 64,5, com carcinomas glóticos tratados por cordectomias totais ou completas (tipo IV) e reconstruídos com retalho de prega vestibular, foram submetidos a videolaringoestroboscopia, onde se avaliou a permeabilidade laríngea, o posicionamento do retalho, o fechamento laríngeo, a movimentação das aritenóides e a característica da fonte sonora: vibrátil ou friccional, e quando vibrátil, a localização e as estruturas que a compunham. A qualidade vocal foi analisada por avaliação perceptiva auditiva e objetiva computadorizada. A função de proteção das vias aéreas durante a deglutição foi realizada pela avaliação endoscópica da deglutição. RESULTADOS: Os resultados evidenciaram que não houve necessidade de manter a traqueostomia no pós-operatório tardio, pois a luz laríngea reconstruída mantinha-se pérvia. A função de proteção estava mantida em todos os casos, a coaptação completa em 30 por cento e somente um paciente teve a movimentação da aritenóide limitada devido à imobilidade do lado operado. Evidenciaram, também, que havia fonte sonora vibrátil em 90 por cento dos casos e que em todos a prega vestibular participava da sua composição. Em sete pacientes a fonte sonora vibrátil se localizava na região glótica. A análise computadorizada revelou freqüência fundamental média de 177,5 Hz, jitter médio de 1,11 por cento e shimmer de 7,04 por cento. Pela escala GRBAS, um paciente apresentou voz normal e 4 tiveram disfonia discreta. CONCLUSÕES: A reconstrução laríngea pós-cordectomia realizada com o retalho da prega vestibular tornou possível emissão de voz normal (freqüência fundamental 205 Hz, jitter 0,13 por cento, shimmer 1,16 por cento), proporcionando coaptação completa em 30 por cento dos casos, fonte sonora vibrátil na região...

Influence of esophageal motility on esophageal speech of laryngectomized patients.

After laryngectomy for treatment of cancer of the larynx, the patient may have vocal rehabilitation by esophageal speech. Some patients fail to achieve the esophageal speech due to reasons involving surgery, radiotherapy, and psychological alterations. Our hypothesis is that the esophageal motility alterations consequent to laryngectomy may be involved in the failure to achieve esophageal speech. Using manometry with continuous perfusion, we studied the esophageal motility of 25 laryngectomized patients, 10 of them able to produce esophageal speech and 15 unable to produce esophageal speech, and 40 asymptomatic normal volunteers. The lower esophageal sphincter (LES) pressure was measured by the rapid pull-through method and the upper esophageal sphincter (UES) pressure by the station pull-through method. The contractions were measured at 5, 10, and 15 cm above the LES after the subjects performed 10 swallows with a 5-mL bolus of water. By comparing volunteers and laryngectomized patients, we found a lower UES pressure, lower amplitude of contractions, and increased percentage of simultaneous contractions in laryngectomized patients (p < 0.05). There was no difference between patients able and unable to produce esophageal speech in LES and UES pressure, esophageal contraction duration and velocity, or in the percentage of failed and simultaneous contractions. The esophageal contraction amplitude was lower in patients who acquired esophageal speech than in patients who did not (p < 0.05 at 10 cm from LES). We conclude that there are esophageal motility alterations in laryngectomized patients but only the decrease of esophageal contraction amplitude seems to be associated with the acquisition of esophageal speech.

Motility of the transverse colon used for esophageal replacement.

The authors studied the motility of transverse colon used for reconstruction of the pharyngogastric transit after esophagectomy. The study included 10 patients who underwent esophagectomy 15 to 201 months (median, 48.5 months) before motility evaluation. Nine patients underwent operation because of caustic injury and one, because of esophageal cancer. The age of the patients ranged from 19 to 54 years (median, 36 years). A manometric esophageal catheter with five side holes spaced 5 cm apart (using the continuous perfusion method) was used to record motility. In three patients, it was not possible to introduce the manometric catheter inside the colon interposition. In the other seven, most of the time there was no contraction when motility was recorded. In four, there was contraction only in the segment 2 to 5 cm below the upper esophageal sphincter. In three, there were peristaltic or simultaneous contractions of long duration, sometimes associated with dry or wet swallows. The motility of colon interposition used to restore transit after esophagectomy is similar to that described for the colon. The contractions may be the consequence of graft distention after successive swallows.

Incidência e diagnóstico da ingestäo de cáustico / Incidence and diagnosis of caustic ingestion

Objetivos: O presente estudo procura identificar a configuraçäo dos pacientes que ingeriram cáustico, de acordo com as variáveis sócio-demográficas, os motivos da ingestäo, a sintomatologia e o diagnóstico. Material e método: A coleta de dados foi feita através dos prontuários de 239 pacientes que ingeriram "soda cáustica". Resultados: Os resultados revelaram que a taxa de incidência de casos atendidos no hospital escoIa foi de 0,5/100.000 habitantes, havendo uma reduçäo de casos na década de 90. As pessoas do sexo feminino foram as o que mais ingeriram cáusticos, 56,9 por cent0 (153) e, quanto aos motivos de ingestäo, 59,8 por cento dos casos foram por tentativa de suicídio e 37,2 por cento, de forma acidental; havendo uma tendência para a diminuiçäo de ingestöes por tentativa de suicídio, na última década. A quantidade de cáustico ingerida variou de "fragmentos" até três colheres de sopa, sendo que entre os suicidas a quantidade tende a ser maior. Conclusäo: Os sintomas apresentados foram dor e vômito, além de sialorréia, disfagia, náuseas e lesöes na cavidade oral. A utilizaçäo dos sinais e sintomas, bem como a quantidade de "soda cáustica" sólida ingerida, parecem ser importantes indicadores do prognóstico e da evoluçäo das lesöes cáusticas. A esofagoscopia determina a severidade das queimaduras, estabelece o tipo de terapêutica a ser usada e estima o prognóstico e o tempo de internaçäo, nos casos de ingestäo de quantidades desconhecidas. O diagnóstico das complicaçöes se faz pelo estudo radiológico, incluindo tomografias, esofagoscopia, gastroscopia e exames laboratoriais

A Lei de Wagner-Grossman é aplicável nas paralisias da laringe? / Is the Wagner-Grossman's law aplicable to laryns paralysis?

Objetivos: O presente trabalho teve como objetivo determinar os fatores que podem influenciar a posiçäo assumida pela prega vocal (PV), em casos de paralisia dos nervos laríngeos recorrente (NLR) e superior (NLS). Material e método: Para tanto, foram utilizados ratos, nos quais se provocou a paralisia da PV de acordo com os seguintes procedimentos: Grupo A: realizados cortes no NLR em alturas diferentes, em 20 ratos; Grupo B: realizados cortes no NLR e de fibras do músculo cricotireóideo, em 15 ratos; Grupo C: realizado corte do NLR, obedecendo o movimento da PV no ciclo respiratório, em 7 ratos. Discussäo: Observou-se que a prega vocal permanecia em posiçäo pára-mediana (PPM) na grande maioria dos casos, mesmo quando as fibras do músculo cricotireóideo foram seccionadas ou o músculo foi denervado. Nesta última situaçäo, observou-se que em 20 por cento dos ratos, a PV se mantinha em posiçäo lateral (PL). Nos casos em que o corte do NLR se fazia segundo o ciclo respiratório, a posiçäo da prega era PPM, mesmo quando o corte ocorria em inspiraçäo. Neste caso, a PV, entäo abduzida, se desloca rapidamente para a linha mediana, como se estivesse sendo puxada. Conclusäo: Conclui-se que, nos ratos, a posiçäo da PV independe da reinervaçäo, da sincinesia e da inervaçäo residual, principalmente do músculo cricotireóideo. O movimento da PV quando da secçäo do NLR durante a inspiraçäo sugere a açäo de forças elásticas

Suporte nutricional a pacientes com câncer de cabeça e pescoço com dieta quimicamente definida por via enteral / Nutritional support to patients with head and neck cancer with chemically defined enteral feeding

A desnutriçäo protéico-enegética é um sério problema que se associa freqüentemente ao câncer e, particularmente, aos de cabeça e pescoço. No presente trabalho, descreve-se a evoluçäo clínico-nutricional de vinte pacientes com doença maligna da cabeça e pescoço que foram sumbmetidos a suporte nutricional enteral com dieta quimicamente definida (aminoácidos, sacarose, vitamina, eletrólitos e elementos traços). A duraçäo do suporte variou entre 12 133 dias, abrangendo o período de hospitalizaçäo para o tratamento cirúrgico. A avaliaçäo da eficiência do suporte foi realizada usando-se a variaçäo dos parâmetros antropométricos e laboratoriais. Os resultados observados demonstram uma média de ganho de pêso de 3.7kg. O ganho de peso que deveu, aparentemente, ao aumento de massa adiposa e massa muscular (prega triciptal: admissäo - 7.03 mm, alta 8.4 mm; circunferência muscular: admissäo - 21.85 cm, alta - 22.72 cm). Näo foram observadas diferenças significativas nos níveis de albumina sérica, capacidade total de ligaçäo ao ferro e contagem de linfócitos. Esses resultados evidenciam que o suporte nutricional agressivo a pacientes com câncer de cabeça e pescoço representa um instrumento terapêutico de valor no combate à desnutriçäo, especialmente no grupo submetido a cirurgias extensas