RESUMO
Juvenile-onset recurrent respiratory papillomatosis (JRRP) is a rare and debilitating childhood disease that presents with recurrent growth of papillomas in the upper airway. Two common human papillomaviruses (HPVs), HPV-6 and -11, are implicated in most cases, but it is still not understood why only a small proportion of children develop JRRP following exposure to these common viruses. We report 2 siblings with a syndromic form of JRRP associated with mild dermatologic abnormalities. Whole-exome sequencing of the patients revealed a private homozygous mutation in NLRP1, encoding Nucleotide-Binding Domain Leucine-Rich Repeat Family Pyrin Domain-Containing 1. We find the NLRP1 mutant allele to be gain of function (GOF) for inflammasome activation, as demonstrated by the induction of inflammasome complex oligomerization and IL-1ß secretion in an overexpression system. Moreover, patient-derived keratinocytes secrete elevated levels of IL-1ß at baseline. Finally, both patients displayed elevated levels of inflammasome-induced cytokines in the serum. Six NLRP1 GOF mutations have previously been described to underlie 3 allelic Mendelian diseases with differing phenotypes and modes of inheritance. Our results demonstrate that an autosomal recessive, syndromic form of JRRP can be associated with an NLRP1 GOF mutation.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Reguladoras de Apoptose/genética , Mutação com Ganho de Função , Homozigoto , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/patologia , Infecções Respiratórias/genética , Infecções Respiratórias/patologia , Pré-Escolar , Citocinas/metabolismo , Feminino , Humanos , Lactente , Inflamassomos , Queratinócitos/citologia , Queratinócitos/imunologia , Queratinócitos/metabolismo , Masculino , Proteínas NLR , Linhagem , Irmãos , SíndromeRESUMO
OBJECTIVE: To investigate the impact of living with a cleft lip and/or cleft palate (CL/P) on sociodemographic variables, quality of life, aesthetics, life satisfaction, and social distress in Dutch-speaking adolescents and adults. DESIGN: Cross-sectional study. PARTICIPANTS: Thirty Dutch-speaking participants with a CL/P with a mean age of 26.93 years (SD = 11.69) and an age- and gender-matched control group of 30 participants (19 men and 11 women) without a CL/P with a mean age of 26.87 years (SD = 11.73). MAIN OUTCOME MEASURES: Self-reported outcomes of sociodemographics, quality of life, aesthetics, life satisfaction, social distress, and impact of cleft on well-being and functioning. RESULTS: No significant differences in educational level, employment, monthly net income, marital status, and having children were found between participants with and without a CL/P. In addition, quality of life, overall aesthetics, life satisfaction, and social distress did not differ between the 2 groups. Among participants with CL/P, there were no gender differences in the influence of their CL/P on daily functioning, well-being, social contacts, family life, applying for a job, work, education, or leisure time. CONCLUSION: The findings revealed no differences between participants with and without a CL/P with regard to sociodemographics, quality of life, aesthetics, life satisfaction, or social distress. There were no gender differences in the influence of cleft on well-being and functioning. Longitudinal research can help determine possible fluctuations in the impact of living with a CL/P across the life span.
Assuntos
Fenda Labial , Fissura Palatina , Adolescente , Adulto , Criança , Estudos Transversais , Estética Dentária , Feminino , Humanos , Masculino , Qualidade de VidaRESUMO
Myhre syndrome is a rare multisystem connective tissue disorder, characterized by short stature, facial dysmorphology, variable intellectual disability, skeletal abnormalities, arthropathy, cardiopathy, laryngotracheal anomalies, and stiff skin. So far, all molecularly confirmed cases harbored a de novo heterozygous gain-of-function mutation in SMAD4, encoding the SMAD4 transducer protein required for both transforming growth factor-beta and bone morphogenic proteins signaling. We report on four novel patients (one female proband and her two affected children, and one male proband) with Myhre syndrome harboring the recurrent c.1486C>T (p.Arg496Cys) mutation in SMAD4. The female proband presented with a congenital heart defect, vertebral anomalies, and facial dysmorphic features. She developed severe tracheal stenosis requiring a total laryngectomy. With assisted reproductive treatment, she gave birth to two affected children. The second proband presented with visual impairment following lensectomy in childhood, short stature, brachydactyly, stiff skin, and decreased peripheral sensitivity. Transmission electron microscopy (TEM) of the dermis shows irregular elastin cores with globular deposits and almost absent surrounding microfibrils and suggests age-related increased collagen deposition. We report on the first familial case of Myhre syndrome and illustrate the variable clinical spectrum of the disorder. Despite the primarily fibrotic nature of the disease, TEM analysis mainly indicates elastic fiber anomalies.
Assuntos
Criptorquidismo/diagnóstico , Transtornos do Crescimento/diagnóstico , Deformidades Congênitas da Mão/diagnóstico , Deficiência Intelectual/diagnóstico , Fenótipo , Adulto , Alelos , Substituição de Aminoácidos , Biópsia , Criptorquidismo/genética , Fácies , Feminino , Genótipo , Transtornos do Crescimento/genética , Deformidades Congênitas da Mão/genética , Humanos , Deficiência Intelectual/genética , Masculino , Pessoa de Meia-Idade , Mutação , Radiografia , Recidiva , Pele/metabolismo , Pele/patologia , Proteína Smad4RESUMO
BACKGROUND/AIMS: This pilot study aimed to evaluate the occurrence of oral habits and non-nutritive sucking habits in children with cleft (lip and) palate (CL/P) between 0-12 years, compared to peers without CL/P. METHODS: Children with CL/P (mean age 6.0 years, SD 2.80) were recruited from the Ghent University Hospital and compared to gender- and age-matched children without CL/P (mean age 5.8 years, SD 3.09). A self-report questionnaire was developed and given to the caregivers. To compare the occurrence of oral habits and non-nutritive sucking habits in children with and without CL/P, χ2 tests or Fisher's exact tests were used. RESULTS: The present study revealed a significantly lower occurrence of non-nutritive sucking habits in children with CL/P. These children showed significantly less pacifier sucking; no significant difference was found regarding thumb or finger sucking nor regarding sucking on other objects. Additionally, the results showed that the occurrence of snoring was statistically significantly higher in children with CL/P. CONCLUSION: Children with CL/P show less non-nutritive sucking habits, but more snoring compared to a control group without CL/P. Although further research regarding the oral habits in children with CL/P is necessary, cleft teams should give attention to the occurrence of oral habits.
Assuntos
Comportamento Infantil , Fenda Labial/psicologia , Fissura Palatina/psicologia , Hábitos , Inquéritos e Questionários , Bruxismo/epidemiologia , Cuidadores , Criança , Pré-Escolar , Feminino , Sucção de Dedo , Humanos , Lactente , Recém-Nascido , Masculino , Chupetas , Projetos Piloto , Autorrelato , Sialorreia/epidemiologia , Ronco/epidemiologia , Comportamento de SucçãoRESUMO
BACKGROUND: To identify predictive factors for the development of late grade 4 mucosal ulcers in adaptive dose-escalated treatments for head-and-neck cancer. MATERIAL AND METHODS: Patient data of four dose-escalated three-phase adaptive dose-painting by numbers (DPBN) clinical trials were analyzed in this study. Correlations between the development of late grade 4 ulcers and factors related with the treatment, disease characteristics and the patient were investigated. Dosimetrical thresholds were searched among the highest doses received by 1.75 cm3 (D1.75cc) of the primary gross tumor volume (GTVT) and the corresponding normalized isoeffective dose (NID21.75cc, with a reference dose of 2Gy/fraction and α/ß of 3 Gy). RESULTS: From 39 studied patients, nine developed late grade 4 mucosal ulcers. The continuation to either smoke or drink alcohol after therapy was the factor that showed a strong (eight out of nine patients) association with the occurrence of grade 4 ulcers. Six of the patients who continued to smoke or/and drink had D1.75cc and NID21.75cc above 84 Gy and 95.5 Gy, respectively. Seven of the patients with grade 4 had the dose levels above these thresholds, but even if the D1.75cc threshold was significant in the prediction of late grade 4 ulcers, it could not be considered as the only contributing factor. CONCLUSIONS: The search for patterns provided strong reasons to apply a dosimetrical threshold for the peak-dose volume of 1.75 cm3 as a preventive measure for late grade 4 mucosal ulcers. Also, patients that continue to smoke or drink alcohol after therapy have increased risk to develop late mucosal ulcers.
Assuntos
Carcinoma de Células Escamosas/radioterapia , Neoplasias de Cabeça e Pescoço/radioterapia , Radioterapia de Intensidade Modulada/efeitos adversos , Úlcera/etiologia , Adulto , Idoso , Fracionamento da Dose de Radiação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Planejamento da Radioterapia Assistida por Computador , Carcinoma de Células Escamosas de Cabeça e PescoçoRESUMO
Intractable aspiration is a serious, often life-threatening condition due to its potential impact on pulmonary function. Aspiration requires therapeutic measures, starting with conservative management but often necessitating surgical treatment. The basic surgical principle is to separate the alimentary and respiratory tracts through a variety of procedures which, unfortunately, nearly all result in the loss of phonation, with the exception of total laryngectomy (TL) which includes the placement of an indwelling voice prosthesis. In this study, we present a modified laryngotracheal separation (LTS) technique that, we believe, offers multiple advantages compared to standard TL. After reviewing the medical records of 35 patients with intractable aspiration who have undergone LTS, we describe the surgical technique and present the postoperative result. In a second surgical procedure about two months following LTS, we aimed to achieve voice restoration by placement of an indwelling voice prosthesis. Intractable aspiration was successfully treated in all patients. Placement of an indwelling voice prosthesis during a second operation was successful in 15 patients, representing the largest reported cohort thus far. LTS is a reliable surgical technique to treat intractable aspiration, with restoration of oral intake, thereby improving the general condition and quality of life of these unfortunate patients. Furthermore, voice restoration can be achieved in selected patients, by placement of a voice prosthesis.
Assuntos
Transtornos de Deglutição/cirurgia , Laringe/cirurgia , Fonação/fisiologia , Pneumonia Aspirativa/etiologia , Procedimentos Cirúrgicos Operatórios/métodos , Traqueia/cirurgia , Distúrbios da Voz/etiologia , Idoso , Transtornos de Deglutição/complicações , Transtornos de Deglutição/fisiopatologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Aspirativa/prevenção & controle , Período Pós-Operatório , Recuperação de Função Fisiológica , Estudos Retrospectivos , Distúrbios da Voz/fisiopatologia , Distúrbios da Voz/cirurgia , Qualidade da Voz/fisiologiaRESUMO
OBJECTIVE: The purpose of this study was to examine the impact of pitch and intensity modulation on nasalance scores. METHODS: A single-group pretest-posttest design was used in which subjects produced reading passages at different pitch and intensity levels. The Nasometer was used for the registration of nasalance scores in subjects with and without cleft palate. RESULTS: An increase in intensity in the non-cleft group resulted in a small but significant decrease in nasalance. Lowering the pitch level resulted in a small but significant decrease in nasalance scores for both the non-cleft and cleft palate subjects. CONCLUSIONS: The nasalance changes after vocal modulations during connected speech are reliable and not biased but the impact of these vocal changes on speech intelligibility and daily communication and the usefulness of these vocal modulations as part of a behavioral management program is not yet proven.
Assuntos
Fissura Palatina/complicações , Inteligibilidade da Fala , Distúrbios da Voz/reabilitação , Qualidade da Voz , Adulto , Fenda Labial/complicações , Fenda Labial/cirurgia , Fissura Palatina/fisiopatologia , Fissura Palatina/cirurgia , Feminino , Humanos , Músculos Laríngeos/fisiopatologia , Masculino , Contração Muscular , Projetos Piloto , Leitura , Fonoterapia , Patologia da Fala e Linguagem/instrumentação , Resultado do Tratamento , Distúrbios da Voz/etiologia , Distúrbios da Voz/fisiopatologia , Adulto JovemRESUMO
About 20% of trans men do not achieve cisgender male frequencies (F0≤131 Hz) after gender-affirming hormone treatment (GAHT) with testosterone. The surgical procedure Isshiki thyroplasty type III (TPIII) is described to lower F0, but data on this technique in trans men are lacking. In this study, 8 trans men, unsatisfied with their voice after a minimum of 12 months of GAHT, underwent TPIII to lower F0 at the Department of Head and Neck Surgery at Ghent University Hospital. TPIII was performed by 1 surgeon using the same method each time. Pre- and postoperatively, an acoustic evaluation of the voice took place. The F0 dropped significantly from the preoperative mean of (154.60 ± 12.29) Hz to the postoperative mean of (105.37 ± 10.52) Hz (t = 9.821, P < .001). TPIII is an effective method for lowering the F0 in trans men who are not satisfied with their voice after long-term GAHT.
Assuntos
Cartilagem Tireóidea/cirurgia , Pessoas Transgênero , Qualidade da Voz , Acústica , Adulto , Bélgica , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Radiation-associated dysphagia (RAD) is highly prevalent in head and neck cancer (HNC) patients, with insufficient tongue strength (TS) as a characteristic of this disabling complication. The effects of tongue-strengthening exercises (TSE) on TS, swallowing, and quality of life (QoL) have not been studied in this population. METHODS: A prospective phase 2 study using an 8 weeks during TSE protocol was carried out in 15 patients with chronic RAD. Outcome parameters were maximal isometric pressure (MIP), TS during swallowing (Pswal), swallowing function, and QoL. All parameters were evaluated at baseline, after 4 and 8 weeks of training, and 4 weeks after the last training session. RESULTS: MIP increased significantly, without detraining effects. Pswal did not increase significantly, but relevant effect sizes were measured. Swallowing function ameliorated, but did not result in increased functional oral intake, self-reported outcome or QoL. CONCLUSION: TSE in patients with RAD results in increased strength and swallowing function.
Assuntos
Transtornos de Deglutição , Qualidade de Vida , Língua , Deglutição , Transtornos de Deglutição/etiologia , Humanos , Estudos Prospectivos , Língua/fisiopatologiaRESUMO
The stigma of a visually prominent facial scar following parotid surgery can be distressing to a young patient. The surgical technique of parotidectomy via a facelift incision is described and evaluated. Thirty patients with a benign lesion of the parotid gland underwent a partial superficial parotidectomy via a modified facelift incision. After operation, all patients had excellent cosmesis and complete function of the facial nerve. The facelift incision provides adequate exposure of the parotid gland for (partial) superficial parotidectomy. It can be offered as an alternative to a select group of patients who present with a small, mobile tumor in the tail of the parotid gland and an explicit request for an invisible postoperative scar.
Assuntos
Estética , Glândula Parótida/cirurgia , Neoplasias Parotídeas/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Adenolinfoma/cirurgia , Adenoma Pleomorfo/cirurgia , Adulto , Idoso , Criança , Pré-Escolar , Cistos/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RitidoplastiaRESUMO
BACKGROUND: Acute and late toxicity after intensity-modulated radiotherapy (IMRT) for head and neck cancer (HNC) impacts on patient quality of life; yet, very late toxicity data remain scarce. This study assessed dysphagia, xerostomia, and neck fibrosis 3-8 years after IMRT. METHODS: A retrospective analysis using generalized estimated equations was performed on 60 patients with HNC treated with fractionated IMRT between 2000 and 2015 who had a follow-up ≥8 years. Toxicity was scored using LENT-SOMA scales. RESULTS: A trend towards a nonlinear global time effect (P = .05) was noted for dysphagia with a decrease during the 5 years post-treatment and an increase thereafter. A significant decrease in xerostomia (P = .001) and an increase in neck fibrosis (P = .04) was observed until 8 years. CONCLUSIONS: Dysphagia, xerostomia, and neck fibrosis do not appear stable over time and remain highly prevalent in the very late follow-up. Our findings support the need for prospective trials investigating very late toxicity in patients with HNC.
Assuntos
Carcinoma de Células Escamosas/radioterapia , Transtornos de Deglutição/radioterapia , Neoplasias de Cabeça e Pescoço/radioterapia , Pescoço/patologia , Radioterapia de Intensidade Modulada/efeitos adversos , Xerostomia/etiologia , Adulto , Idoso , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Estudos de Coortes , Transtornos de Deglutição/epidemiologia , Transtornos de Deglutição/fisiopatologia , Feminino , Fibrose/epidemiologia , Fibrose/etiologia , Fibrose/fisiopatologia , Seguimentos , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/métodos , Estudos Retrospectivos , Medição de Risco , Fatores de Tempo , Resultado do Tratamento , Xerostomia/epidemiologia , Xerostomia/fisiopatologiaRESUMO
PURPOSE: To compare the effectiveness of intensity-modulated radiotherapy (IMRT) and conventional (two-dimensional) radiotherapy in the treatment of cervical lymph node metastases from unknown primary cancer (UPC). METHODS AND MATERIALS: Between February 2003 and September 2006, 23 patients with UPC of squamous cell carcinoma were treated with IMRT. Extended putative mucosal and bilateral nodal sites were irradiated to a median dose of 66 Gy. In 19 patients, IMRT was performed after lymph node dissection, and in 4 patients primary radiotherapy was given. The conventional radiotherapy group (historical control group) comprised 18 patients treated to a median dose of 66 Gy between August 1994 and October 2003. RESULTS: Twenty patients completed treatment. As compared with conventional radiotherapy, the incidence of Grade 3 acute dysphagia was significantly lower in the IMRT group (4.5% vs. 50%, p = 0.003). By 6 months, Grade 3 xerostomia was detected in 11.8% patients in the IMRT group vs. 53.4% in the historical control group (p = 0.03). No Grade 3 dysphagia or skin fibrosis was observed after IMRT but these were noted after conventional radiotherapy (26.7%, p = 0.01) and 26.7%, p = 0.03) respectively). With median follow-up of living patients of 17 months, there was no emergence of primary cancer. One patient had persistent nodal disease and another had nodal relapse at 5 months. Distant metastases were detected in 4 patients. The 2-year overall survival and distant disease-free probability after IMRT did not differ significantly from those for conventional radiotherapy (74.8% vs. 61.1% and 76.3% vs. 68.4%, respectively). CONCLUSIONS: Use of IMRT for UPC resulted in lower toxicity than conventional radiotherapy, and was similar in efficacy.
Assuntos
Carcinoma de Células Escamosas/radioterapia , Neoplasias de Cabeça e Pescoço/radioterapia , Neoplasias Primárias Desconhecidas/radioterapia , Radioterapia Conformacional/métodos , Idoso , Idoso de 80 Anos ou mais , Vértebras Cervicais , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
A number of studies have evaluated the effectiveness of a cricothyroid approximation (CA) in creating a more female voice in male-to-female transsexuals (MFTs) from an acoustic perspective. An increase in pitch is of little value, however, unless it accurately indicates listeners' perceptions of gender. The purpose of this study was to further investigate the effectiveness of a CA in feminizing the voice from a perceptual perspective. Video recordings of nine MFTs, nine nontranssexual males (NTMs), and nine nontranssexual females (NTFs) were presented twice to the panel of judges in a randomized order: first auditory only (only hearing a subject's speech) and subsequently audiovisual (hearing and seeing a subject's speech). The panel of judges, 42 students (21 female, 21 male) from different disciplines, rated the participants' voices on a 100-mm visual analog scale with "very male" and "very female" as left and right extremes, respectively. The group of MFT obtained scores that were situated in between those of the NTM and the NTF, both for the auditory only and the audiovisual mode of presentation. Perception of femaleness significantly correlated with average fundamental frequency for both modes of presentation. It can be concluded that a CA approximation is a viable option to raise the voice pitch in MFTs but that this surgery alone may not be sufficient to create a voice that is perceived as a totally female.
Assuntos
Cartilagem Cricoide/cirurgia , Caracteres Sexuais , Cartilagem Tireóidea/cirurgia , Transexualidade/cirurgia , Qualidade da Voz , Adolescente , Adulto , Feminino , Humanos , Julgamento , Masculino , Pessoa de Meia-Idade , Valores de Referência , Espectrografia do SomRESUMO
OBJECTIVE: The main purpose of this study is to determine the treatment effectiveness of pharyngeal flap surgery by measuring speech outcome 1 year after surgery. The authors hypothesized that flap surgery is an effective technique for velopharyngeal inadequacy resulting in improved intelligibility, decreased hypernasality and nasalance scores and normal voice characteristics. PATIENTS AND METHODS: Objective (Nasometer, Dysphonia Severity Index) as well as subjective (perceptual evaluations) assessment techniques were performed in 7 subjects. Speech evaluations were performed 1 year after flap surgery and comparison was made between the speech results of the preoperative condition (1 week before surgery) and the first postoperative condition (6 weeks after surgery). RESULTS: After pharyngeal flap surgery there was improved though still slightly impaired intelligibility, with normal nasality, normal nasalance values for standard Flemish speech and normal voice characteristics. The normal nasality and nasalance values were not present in the preoperative condition. Persistence of the incorrect production of the thrill sound /r/ and the fricatives /s/ and /sch/ were observed. CONCLUSION: It is likely that the slightly impaired speech intelligibility is determined by the presence of persistent articulation disorders.
Assuntos
Fissura Palatina/cirurgia , Faringe/cirurgia , Inteligibilidade da Fala , Retalhos Cirúrgicos , Distúrbios da Voz/cirurgia , Voz/fisiologia , Adenoidectomia , Bélgica , Criança , Disfonia/etiologia , Seguimentos , Humanos , Fonação , Fonética , Projetos Piloto , Estudos Retrospectivos , Acústica da Fala , Testes de Articulação da Fala , Distúrbios da Fala/cirurgiaRESUMO
OBJECTIVE AND SUBJECTS: Speech outcomes were described for 16 patients with cleft palate (mean age: 5.4 years) following Sommerlad primary palatoplasty performed by a single surgeon of the Ghent University Hospital. These speech outcomes were compared with those of an age and gender matched control group without cleft palate (mean age: 5.3 years). METHODS: Speech intelligibility/distinctiveness, resonance, nasal airflow and articulation, were perceptually evaluated. Additionally, nasalance values and the NSI 2.0 were determined. RESULTS: In seven patients, speech intelligibility/distinctiveness was disordered. Hypernasality was present in twelve participants, whereas nasal emission and nasal turbulence were perceived in thirteen and five patients respectively. Both perceptual and instrumental speech evaluations were significantly poorer in the patient group in comparison to the control group. CONCLUSIONS: Patients still present with both obligatory and compensatory speech disorders following Sommerlad's palatoplasty. In the future, a Dutch speech assessment protocol will be developed in order to standardize follow-up of these patients and to allow for within-center and inter-center comparisons.
Assuntos
Transtornos da Articulação/cirurgia , Fissura Palatina/cirurgia , Hospitais Universitários , Inteligibilidade da Fala , Pré-Escolar , Fenda Labial/cirurgia , Feminino , Humanos , Masculino , Países Baixos , Resultado do Tratamento , Insuficiência Velofaríngea/etiologia , Insuficiência Velofaríngea/cirurgia , Distúrbios da Voz/etiologia , Distúrbios da Voz/cirurgiaRESUMO
PURPOSE: To assess the feasibility of intensity-modulated radiotherapy (IMRT) using positron emission tomography (PET)-guided dose escalation, and to determine the maximum tolerated dose in head and neck cancer. METHODS AND MATERIALS: A Phase I clinical trial was designed to escalate the dose limited to the [(18)-F]fluoro-2-deoxy-D-glucose positron emission tomography ((18)F-FDG-PET)-delineated subvolume within the gross tumor volume. Positron emission tomography scanning was performed in the treatment position. Intensity-modulated radiotherapy with an upfront simultaneously integrated boost was employed. Two dose levels were planned: 25 Gy (level I) and 30 Gy (level II), delivered in 10 fractions. Standard IMRT was applied for the remaining 22 fractions of 2.16 Gy. RESULTS: Between 2003 and 2005, 41 patients were enrolled, with 23 at dose level I, and 18 at dose level II; 39 patients completed the planned therapy. The median follow-up for surviving patients was 14 months. Two cases of dose-limiting toxicity occurred at dose level I (Grade 4 dermitis and Grade 4 dysphagia). One treatment-related death at dose level II halted the study. Complete response was observed in 18 of 21 (86%) and 13 of 16 (81%) evaluated patients at dose levels I and II (p < 0.7), respectively, with actuarial 1-year local control at 85% and 87% (p = n.s.), and 1-year overall survival at 82% and 54% (p = 0.06), at dose levels I and II, respectively. In 4 of 9 patients, the site of relapse was in the boosted (18)F-FDG-PET-delineated region. CONCLUSIONS: For head and neck cancer, PET-guided dose escalation appears to be well-tolerated. The maximum tolerated dose was not reached at the investigated dose levels.
Assuntos
Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/radioterapia , Tomografia por Emissão de Pósitrons/métodos , Radioterapia de Intensidade Modulada/métodos , Adulto , Idoso , Intervalo Livre de Doença , Estudos de Viabilidade , Feminino , Fluordesoxiglucose F18 , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Compostos Radiofarmacêuticos , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/efeitos adversos , Falha de TratamentoRESUMO
PURPOSE/OBJECTIVE: The benefit of upfront neck dissection (ND) in locally advanced head and neck squamous cell carcinoma (HNSCC) treated with primary (chemo-) radiotherapy (R(C)T) is debated. Therefore, we retrospectively compared disease control and toxicity between patients who were treated with and without upfront ND followed by R(C)T. MATERIAL/METHODS: Two-hundred sixty-four consecutive patients with HNSCC without distant metastases at diagnosis and with lymph node stage N2-N3 were included in 2 centers. Patients were all treated between January 2002 and December 2012, and received definitive R(C)T in center 1 and upfront ND followed by R(C)T in center 2. Clinical data and outcome were assessed retrospectively. Toxicity was scored using the LENT-SOMA scale at 6, 12, 18 and 24months following the end of treatment. RESULTS: We included 150 patients in the group without ND (center 1) and 114 patients in the group with upfront ND (center 2). Mean follow up was 5.68years in the group without ND and 5.83years in the group with upfront ND. Local, regional and distant control after 2years were 91.07% and 85.96% (p=0.09), 89.22% and 83.27% (p=0.12) and 76.74% and 75.13% (p=0.92) in the group with and without upfront ND, respectively. We did not find a significant difference between both groups regarding edema and atrophy at 6, 12, 18 and 24months. We found a trend at all time-points toward worse outcome in the ND group at all time-points (p=0.06). A significantly higher proportion of moderate to severe fibrosis (grade ≥2) was present in the ND group (p=0.01) at all time points. CONCLUSION: There was no significant difference in local, regional or distant control and disease-free survival between both patient populations. Fibrosis, specifically fibrosis grade ≥2 is more prominent following upfront ND and R(C)T when compared to R(C)T alone.
Assuntos
Carcinoma de Células Escamosas/terapia , Neoplasias de Cabeça e Pescoço/terapia , Esvaziamento Cervical/métodos , Adulto , Idoso , Carcinoma de Células Escamosas/patologia , Quimiorradioterapia , Intervalo Livre de Doença , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e PescoçoRESUMO
BACKGROUND: Most trials in head and neck cancer emphasize locoregional control, as this is the main pattern of therapy failure. However, up to 15% of patients develop distant metastases. The purpose of this study was to present the investigated factors associated with distant metastasis in a single-center patient cohort. METHODS: A retrospective analysis of a single-center patient cohort over an 18-year period has been performed. We report on prevalence and incidence of distant metastasis, timing in relation to locoregional failure, Kaplan-Meier analysis for actuarial distant control rates, and univariate analysis taking into account histological, etiologic, surgical, site-dependent, stage-dependent characteristics, modality of primary therapy, and locoregional control. RESULTS: Of 1022 patients, 141 (13.8%) were diagnosed with distant metastases involving 283 sites. Actuarial rates of distant control were 88%, 84%, 80%, and 79% at 1, 2, 5, and 10 years, respectively. Factors associated with distant metastasis are stage grouping and regional node positivity, extranodal extension, locoregional residual disease, and human papillomavirus (HPV) negative status in oropharyngeal squamous cell carcinoma. CONCLUSION: Distant metastases in head and neck cancer led to dismal prognosis. Factors associated with distant metastasis are related to characteristics of the primary tumor. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1733-1743, 2017.
Assuntos
Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Causas de Morte , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Metástase Linfática/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Bélgica , Carcinoma de Células Escamosas/terapia , Estudos de Coortes , Bases de Dados Factuais , Intervalo Livre de Doença , Feminino , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Medição de Risco , Carcinoma de Células Escamosas de Cabeça e Pescoço , Análise de SobrevidaRESUMO
BACKGROUND: The purpose of this study was to report the long-term outcome of 18 F-fluorodeoxyglucose-positron emission tomography (18 F-FDG-PET)-guided dose painting for head and neck cancer in comparison to conventional intensity-modulated radiotherapy (IMRT) in a matched case-control study. METHODS: Seventy-two patients with nonmetastatic head and neck cancer treated with dose painting were compared with 72 control patients matched on tumor site and T classification. Either 18 F-FDG-PET-guided dose painting by contour (DPBC) or voxel intensity-based dose painting by number (DPBN) was performed; control patients underwent standard IMRT. A total median dose to the dose-painted target was 70.2-85.9 Gy/30-32 fractions versus 69.1 Gy/32 fractions with conventional IMRT. In 31 patients, dose painting was adapted to per-treatment changes in the tumor and organs-at-risk (OAR). RESULTS: Median follow-up in living dose-painting and control patients was 87.7 months (range 56.1-119.3) and 64.8 months (range 46.3-83.4), respectively. Five-year local control rates in the dose-painting patients were 82.3% against 73.6% in the control (P = .36); in patients treated to normalized isoeffective doses >91 Gy (NID2Gy) local control reached 85.7% at 5 years against 73.6% in the control group (P =.39). There was no difference in regional (P = .82) and distant control (P = .78). Five-year overall and disease-specific survival rates were 36.3% versus 38.1% (P = .50) and 56.5% versus 51.7% (P = .72), respectively. A half of the dose-painting patients developed acute grade ≥3 dysphagia (P = .004). Late grade 4 mucosal ulcers at the site of dose escalation in 9 of 72 patients was the most common severe toxicity with dose painting versus 3 of 72 patients with conventional IMRT (P = .11). Patients in the dose-painting group had increased rates of acute and late dysphagia (P = .004 and P = .005). CONCLUSION: Dose-painting strategies can be used to increase dose to specific tumor subvolumes. Five-year local, regional, and distant control rates are comparable with patients treated with conventional IMRT. Volume and intensity of dose escalation should be further tailored, given the possible increase in severe acute and chronic toxicity. Adapting treatment and decreasing dose to the swallowing structures might contribute to lower toxicity rates when applied in smaller tumor volumes. Whether adaptive DPBN can significantly improve outcomes is currently being investigated in a novel clinical trial.
Assuntos
Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/radioterapia , Fluordesoxiglucose F18 , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/radioterapia , Tomografia por Emissão de Pósitrons , Planejamento da Radioterapia Assistida por Computador , Radioterapia de Intensidade Modulada , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/mortalidade , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Dosagem Radioterapêutica , Carcinoma de Células Escamosas de Cabeça e Pescoço , Taxa de Sobrevida , Resultado do TratamentoRESUMO
We present a case of a 66-year-old Caucasian man with acute respiratory distress. The patient had a history of multiple cerebrovascular accidents which resulted in left hemiplegia, swallowing problems, and aphasia. He was tentatively diagnosed with aspiration pneumonia. However, because of clinical deterioration further investigations concluded to the aspiration of a dental prosthesis. After intubation and stabilization, the prosthesis could be manually extracted. However, the patient developed a Staphylococcus epidermidis sepsis and despite adequate antibiotic therapy, he eventually died. Dental prosthesis aspiration is a medical situation associated with a higher morbidity and mortality rate compared to ingested foreign bodies. It requires a high level of suspicion to ensure a timely diagnosis and life-saving treatment. Thorough history taking is of great importance in case of tracheobronchial aspiration, which is in the adult population mostly secondary to an underlying disorder. In impaired adults with missing dental prostheses there should be extra awareness for this problem. This case report illustrates the importance of a detailed history in case of tracheobronchial aspiration and shows the limitations in the diagnostic usefulness of bedside chest radiography.