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Objectives Malignant tumors of the sinonasal cavities with extension to the frontal skull base are rare and challenging pathologies. Combined-approach surgery using a frontobasal craniotomy and endoscopic sinus surgery with reconstruction of the anterior skull base followed by adjuvant radiotherapy is a preferred treatment strategy in selected cases. Morbidity and mortality rates are high in this population. We aim to add our experience to the current literature. Design We performed a retrospective cross-sectional single center study of the long-term clinical outcome in a tertiary university referral hospital in the Netherlands between 2010 and 2021. Descriptive statistics and frequency distributions were performed Participants Patient, tumor, treatment, complications and survival characteristics of eighteen consecutive patients were extracted from the electronic health records. Main Outcome Measures The primary outcome measures are progression free survival, overall survival and complication rate. Results Eighteen consecutive patients were included with a mean age of 61 (SD ± 10) years (range 38-80); ten males and eight females. Gross total resection was achieved in 14 (77%) patients. Eleven (61%) patients underwent local radiotherapy, one (5%) chemotherapy and three (17%) a combination of both. Mean follow-up duration was 49 months (range 3 - 138). Three (17%) patients died in hospital due to post-operative complications. Six (33%) patients died during follow-up due to disease progression. Mean progression-free survival was 47 months (range 0 - 113). Conclusion In conclusion, the overall survival was 50% for this group of patients with large sinonasal tumors. Progressive disease affects survival rate severely. Surgical complications were seen in five (28%) patients. Radiotherapy is associated with high complication rates. Radiation necrosis was a serious complication in two patients and could be treated with high dose steroids.
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Human Papilloma Virus (HPV)-associated oropharyngeal squamous cell cancer (OPSCC) represents an OPSCC subgroup with an overall good prognosis with a rising incidence in Western countries. Multiple lines of evidence suggest that HPV-associated tumors are not a homogeneous tumor entity, underlining the need for accurate prognostic biomarkers. In this retrospective, multi-institutional study involving 906 patients from four centers and one database, we developed a deep learning algorithm (OPSCCnet), to analyze standard H&E stains for the calculation of a patient-level score associated with prognosis, comparing it to combined HPV-DNA and p16-status. When comparing OPSCCnet to HPV-status, the algorithm showed a good overall performance with a mean area under the receiver operator curve (AUROC) = 0.83 (95% CI = 0.77-0.9) for the test cohort (n = 639), which could be increased to AUROC = 0.88 by filtering cases using a fixed threshold on the variance of the probability of the HPV-positive class - a potential surrogate marker of HPV-heterogeneity. OPSCCnet could be used as a screening tool, outperforming gold standard HPV testing (OPSCCnet: five-year survival rate: 96% [95% CI = 90-100%]; HPV testing: five-year survival rate: 80% [95% CI = 71-90%]). This could be confirmed using a multivariate analysis of a three-tier threshold (OPSCCnet: high HR = 0.15 [95% CI = 0.05-0.44], intermediate HR = 0.58 [95% CI = 0.34-0.98] p = 0.043, Cox proportional hazards model, n = 211; HPV testing: HR = 0.29 [95% CI = 0.15-0.54] p < 0.001, Cox proportional hazards model, n = 211). Collectively, our findings indicate that by analyzing standard gigapixel hematoxylin and eosin (H&E) histological whole-slide images, OPSCCnet demonstrated superior performance over p16/HPV-DNA testing in various clinical scenarios, particularly in accurately stratifying these patients.
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BACKGROUND: T4-classified squamous cell carcinoma (SCC) of external auditory canal (EAC) can potentially involve different anatomical structures, which could translate into different treatment strategies and survival outcomes within one classification. Our aim is to evaluate the clinical added value of T4-subclasses proposed by Lavieille and by Zanoletti. METHODS: Retrospective data, including patients with primary operated cT4-classified EAC SCC, was obtained from 12 international hospitals. We subclassified according to the T4-subclasses. The treatment strategies, disease-free survival (DFS) and overall survival per subclass were calculated. RESULTS: A total of 130 T4-classified EAC SCC were included. We found commonly used treatment strategies per subclass according to Lavieille and the DFS seems also to differ per subclass. Subclass according to Zanoletti showed comparable treatment strategies and survival outcomes per subclass. CONCLUSION: Our study suggests that the subclass according Lavieille might have added value in clinical practice to improve care of T4-classified EAC SCC.
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Carcinoma de Células Escamosas , Neoplasias da Orelha , Carcinoma de Células Escamosas/patologia , Meato Acústico Externo/patologia , Neoplasias da Orelha/patologia , Humanos , Estadiamento de Neoplasias , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Radical resection for patients with oral cavity cancer remains challenging. Rapid evaporative ionization mass spectrometry (REIMS) of electrosurgical vapors has been reported for real-time classification of normal and tumor tissues for numerous surgical applications. However, the infiltrative pattern of invasion of oral squamous cell carcinomas (OSCC) challenges the ability of REIMS to detect low amounts of tumor cells. We evaluate REIMS sensitivity to determine the minimal amount of detected tumors cells during oral cavity cancer surgery. A total of 11 OSCC patients were included in this study. The tissue classification based on 185 REIMS ex vivo metabolic profiles from five patients was compared to histopathology classification using multivariate analysis and leave-one-patient-out cross-validation. Vapors were analyzed in vivo by REIMS during four glossectomies. Complementary desorption electrospray ionization-mass spectrometry imaging (DESI-MSI) was employed to map tissue heterogeneity on six oral cavity sections to support REIMS findings. REIMS sensitivity was assessed with a new cell-based assay consisting of mixtures of cell lines (tumor, myoblasts, keratinocytes). Our results depict REIMS classified tumor and soft tissues with 96.8% accuracy. In vivo REIMS generated intense mass spectrometric signals. REIMS detected 10% of tumor cells mixed with 90% myoblasts with 83% sensitivity and 82% specificity. DESI-MSI underlined distinct metabolic profiles of nerve features and a metabolic shift phosphatidylethanolamine PE(O-16:1/18:2))/cholesterol sulfate common to both mucosal maturation and OSCC differentiation. In conclusion, the assessment of tissue heterogeneity with DESI-MSI and REIMS sensitivity with cell mixtures characterized sensitive metabolic profiles toward in vivo tissue recognition during oral cavity cancer surgeries.
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Metabolômica , Neoplasias Bucais , Humanos , Espectrometria de Massas/métodos , Neoplasias Bucais/cirurgia , Análise Multivariada , Espectrometria de Massas por Ionização por Electrospray/métodosRESUMO
BACKGROUND: The prognostic reliability of the UICC's TNM classification (8th edition) for human papillomavirus (HPV)-positive tonsillar squamous cell carcinomas (TSCCs) compared to the 7th edition was explored, and its improvement by using additional anatomical and nonanatomical parameters. METHODS: One hundred and ten HPV-positive and 225 HPV-negative TSCCs were retrospectively analyzed. Survival was correlated with patient and tumor characteristics (7th and 8th edition UICC TNM classification). RESULTS: In HPV-positive TSCCs, the 8th edition UICC's TNM classification correlated better with prognosis than the 7th edition. Also, smoking status was a stronger prognosticator of survival than UICC staging. Non- or former smokers had a 5-year overall survival of 95.1% regardless of tumor stage. Furthermore, age (>65 years), cN3, and M1 classification were significant prognostic factors. CONCLUSION: The prognostic value of the 8th edition UICC's TNM classification improved significantly when compared to the 7th edition. Nonetheless, further improvement is possible by adding nonanatomical factors (smoking, age >65 year) and separating N0-N2 from N3.
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Alphapapillomavirus , Carcinoma de Células Escamosas , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Idoso , Carcinoma de Células Escamosas/patologia , Humanos , Estadiamento de Neoplasias , Neoplasias Orofaríngeas/patologia , Papillomaviridae , Infecções por Papillomavirus/patologia , Prognóstico , Reprodutibilidade dos Testes , Estudos RetrospectivosRESUMO
BACKGROUND: Human papilloma virus infection is known to influence oropharyngeal cancer (OPC) risk, likely via sexual transmission. However, sexual behaviour has been correlated with other risk factors including smoking and alcohol, meaning independent effects are difficult to establish. We aimed to evaluate the causal effect of sexual behaviour on the risk of OPC using Mendelian randomization (MR). METHODS: Genetic variants robustly associated with age at first sex (AFS) and the number of sexual partners (NSP) were used to perform both univariable and multivariable MR analyses with summary data on 2641 OPC cases and 6585 controls, obtained from the largest available genome-wide association studies (GWAS). Given the potential for genetic pleiotropy, we performed a number of sensitivity analyses: (i) MR methods to account for horizontal pleiotropy, (ii) MR of sexual behaviours on positive (cervical cancer and seropositivity for Chlamydia trachomatis) and negative control outcomes (lung and oral cancer), (iii) Causal Analysis Using Summary Effect estimates (CAUSE), to account for correlated and uncorrelated horizontal pleiotropic effects, (iv) multivariable MR analysis to account for the effects of smoking, alcohol, risk tolerance and educational attainment. RESULTS: In univariable MR, we found evidence supportive of an effect of both later AFS (IVW OR = 0.4, 95%CI (0.3, 0.7), per standard deviation (SD), p = < 0.001) and increasing NSP (IVW OR = 2.2, 95%CI (1.3, 3.8) per SD, p = < 0.001) on OPC risk. These effects were largely robust to sensitivity analyses accounting for horizontal pleiotropy. However, negative control analysis suggested potential violation of the core MR assumptions and subsequent CAUSE analysis implicated pleiotropy of the genetic instruments used to proxy sexual behaviours. Finally, there was some attenuation of the univariable MR results in the multivariable models (AFS IVW OR = 0.7, 95%CI (0.4, 1.2), p = 0.21; NSP IVW OR = 0.9, 95%CI (0.5 1.7), p = 0.76). CONCLUSIONS: Despite using genetic variants strongly related sexual behaviour traits in large-scale GWAS, we found evidence for correlated pleiotropy. This emphasizes a need for multivariable approaches and the triangulation of evidence when performing MR of complex behavioural traits.
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Análise da Randomização Mendeliana , Neoplasias Orofaríngeas , Estudo de Associação Genômica Ampla , Humanos , Análise da Randomização Mendeliana/métodos , Neoplasias Orofaríngeas/epidemiologia , Neoplasias Orofaríngeas/genética , Polimorfismo de Nucleotídeo Único , Comportamento Sexual , Fumar/efeitos adversos , Fumar/epidemiologiaRESUMO
Although several oropharyngeal cancer (OPC) susceptibility loci have been identified, most previous studies lacked detailed information on human papillomavirus (HPV) status. We conduct a genome-wide analysis by HPV16 serology status in 4,002 oral cancer cases (OPC and oral cavity cancer (OCC)) and 5,256 controls. We detect four susceptibility loci pointing to a distinct genetic predisposition by HPV status. Our most notable finding in the HLA region, that is now confirmed to be specific of HPV(+)OPC risk, reveal two independent loci with strong protective effects, one refining the previously reported HLA class II haplotype association. Antibody levels against HPV16 viral proteins strongly implicate the protective HLA variants as major determinants of humoral response against L1 capsid protein or E6 oncoprotein suggesting a natural immune response against HPV(+)OPC promoted by HLA variants. This indicates that therapeutic vaccines that target E6 and attenuate viral response after established HPV infections might protect against HPV(+)OPC.
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Antígenos HLA/imunologia , Papillomavirus Humano 16/imunologia , Imunidade Humoral , Neoplasias Bucais/imunologia , Neoplasias Orofaríngeas/imunologia , Infecções por Papillomavirus/imunologia , Idoso , Anticorpos Antivirais/biossíntese , Proteínas do Capsídeo/genética , Proteínas do Capsídeo/imunologia , Estudos de Casos e Controles , Feminino , Expressão Gênica , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Antígenos HLA/classificação , Antígenos HLA/genética , Haplótipos , Papillomavirus Humano 16/patogenicidade , Humanos , Masculino , Metanálise como Assunto , Pessoa de Meia-Idade , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Neoplasias Bucais/virologia , Proteínas Oncogênicas Virais/genética , Proteínas Oncogênicas Virais/imunologia , Neoplasias Orofaríngeas/genética , Neoplasias Orofaríngeas/patologia , Neoplasias Orofaríngeas/virologia , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Locos de Características Quantitativas , Proteínas Repressoras/genética , Proteínas Repressoras/imunologia , Fatores de Risco , Fumar/fisiopatologiaRESUMO
Head and neck squamous cell carcinoma (HNSCC), which includes cancers of the oral cavity and oropharynx, is a cause of substantial global morbidity and mortality. Strategies to reduce disease burden include discovery of novel therapies and repurposing of existing drugs. Statins are commonly prescribed for lowering circulating cholesterol by inhibiting HMG-CoA reductase (HMGCR). Results from some observational studies suggest that statin use may reduce HNSCC risk. We appraised the relationship of genetically-proxied cholesterol-lowering drug targets and other circulating lipid traits with oral (OC) and oropharyngeal (OPC) cancer risk using two-sample Mendelian randomization (MR). For the primary analysis, germline genetic variants in HMGCR, NPC1L1, CETP, PCSK9 and LDLR were used to proxy the effect of low-density lipoprotein cholesterol (LDL-C) lowering therapies. In secondary analyses, variants were used to proxy circulating levels of other lipid traits in a genome-wide association study (GWAS) meta-analysis of 188,578 individuals. Both primary and secondary analyses aimed to estimate the downstream causal effect of cholesterol lowering therapies on OC and OPC risk. The second sample for MR was taken from a GWAS of 6,034 OC and OPC cases and 6,585 controls (GAME-ON). Analyses were replicated in UK Biobank, using 839 OC and OPC cases and 372,016 controls and the results of the GAME-ON and UK Biobank analyses combined in a fixed-effects meta-analysis. We found limited evidence of a causal effect of genetically-proxied LDL-C lowering using HMGCR, NPC1L1, CETP or other circulating lipid traits on either OC or OPC risk. Genetically-proxied PCSK9 inhibition equivalent to a 1 mmol/L (38.7 mg/dL) reduction in LDL-C was associated with an increased risk of OC and OPC combined (OR 1.8 95%CI 1.2, 2.8, p = 9.31 x10-05), with good concordance between GAME-ON and UK Biobank (I2 = 22%). Effects for PCSK9 appeared stronger in relation to OPC (OR 2.6 95%CI 1.4, 4.9) than OC (OR 1.4 95%CI 0.8, 2.4). LDLR variants, resulting in genetically-proxied reduction in LDL-C equivalent to a 1 mmol/L (38.7 mg/dL), reduced the risk of OC and OPC combined (OR 0.7, 95%CI 0.5, 1.0, p = 0.006). A series of pleiotropy-robust and outlier detection methods showed that pleiotropy did not bias our findings. We found limited evidence for a role of cholesterol-lowering in OC and OPC risk, suggesting previous observational results may have been confounded. There was some evidence that genetically-proxied inhibition of PCSK9 increased risk, while lipid-lowering variants in LDLR, reduced risk of combined OC and OPC. This result suggests that the mechanisms of action of PCSK9 on OC and OPC risk may be independent of its cholesterol lowering effects; however, this was not supported uniformly across all sensitivity analyses and further replication of this finding is required.
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Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Pró-Proteína Convertase 9/genética , Receptores de LDL/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Colesterol/biossíntese , Colesterol/genética , Proteínas de Transferência de Ésteres de Colesterol/genética , LDL-Colesterol/antagonistas & inibidores , LDL-Colesterol/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Mutação em Linhagem Germinativa/genética , Humanos , Hidroximetilglutaril-CoA Redutases/efeitos dos fármacos , Hidroximetilglutaril-CoA Redutases/genética , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Proteínas de Membrana Transportadoras/genética , Análise da Randomização Mendeliana , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologiaRESUMO
Squamous cell carcinomas (SqCC) of the aerodigestive tract have similar etiological risk factors. Although genetic risk variants for individual cancers have been identified, an agnostic, genome-wide search for shared genetic susceptibility has not been performed. To identify novel and pleotropic SqCC risk variants, we performed a meta-analysis of GWAS data on lung SqCC (LuSqCC), oro/pharyngeal SqCC (OSqCC), laryngeal SqCC (LaSqCC) and esophageal SqCC (ESqCC) cancers, totaling 13,887 cases and 61,961 controls of European ancestry. We identified one novel genome-wide significant (Pmeta<5x10-8) aerodigestive SqCC susceptibility loci in the 2q33.1 region (rs56321285, TMEM273). Additionally, three previously unknown loci reached suggestive significance (Pmeta<5x10-7): 1q32.1 (rs12133735, near MDM4), 5q31.2 (rs13181561, TMEM173) and 19p13.11 (rs61494113, ABHD8). Multiple previously identified loci for aerodigestive SqCC also showed evidence of pleiotropy in at least another SqCC site, these include: 4q23 (ADH1B), 6p21.33 (STK19), 6p21.32 (HLA-DQB1), 9p21.33 (CDKN2B-AS1) and 13q13.1(BRCA2). Gene-based association and gene set enrichment identified a set of 48 SqCC-related genes rel to DNA damage and epigenetic regulation pathways. Our study highlights the importance of cross-cancer analyses to identify pleiotropic risk loci of histology-related cancers arising at distinct anatomical sites.
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Carcinoma de Células Escamosas/genética , Neoplasias do Sistema Digestório/genética , Loci Gênicos , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Alelos , Biomarcadores Tumorais , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Neoplasias do Sistema Digestório/metabolismo , Neoplasias do Sistema Digestório/patologia , Genótipo , Humanos , Razão de Chances , Transdução de SinaisRESUMO
BACKGROUND: Squamous cell carcinoma (SCC) of the external auditory canal (EAC) is a rare disease, which is commonly classified with the modified Pittsburgh classification. Our aim was to evaluate the predictive performance of this classification in relation to disease-free survival (DFS). METHODS: We examined retrospective data from a nationwide Dutch cohort study including patients with primary EAC SCC. These data were combined with individual patient data from the literature. Using the combined data, the predictive performances were calculated using the c-index. RESULTS: A total of 381 patients were included, 294 for clinical and 281 for the pathological classification analyses. The c-indices of the clinical and the pathological modified Pittsburgh classification predicting DFS were 0.725 (0.668-0.782) and 0.729 (0.672-0.786), respectively. CONCLUSION: The predictive performance of the modified Pittsburgh classification system as such appears to be acceptable to predict the DFS of EAC SCC. Other factors need to be added to a future model to improve the predicted performance.
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Carcinoma de Células Escamosas , Neoplasias da Orelha , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Estudos de Coortes , Intervalo Livre de Doença , Meato Acústico Externo/patologia , Neoplasias da Orelha/patologia , Humanos , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Resultado do TratamentoRESUMO
PURPOSE: Debate on the extent of treatment of neck metastasis of cancer of unknown primary tumors (CUPs) is still ongoing. In two Dutch tertiary referral centers, the post-surgical radiation target volume changed from the bilateral neck including the pharyngeal axis to the unilateral neck only, in the course of the last decade. This study aims to investigate the outcome of patients with CUP before and after de-escalation of post-surgical radiotherapy. METHODS: Data of two Dutch tertiary referral centers were merged. Disease-free survival (DFS), overall survival (OS), and regional control rate (RCR) of 80 patients diagnosed with CUP (squamous cell and undifferentiated carcinomas) between 1990 and 2009 were retrospectively analyzed. RESULTS: Thirty patients received bilateral neck and pharyngeal axis radiotherapy and 42 patients ipsilateral radiotherapy only. In another eight patients, the postsurgical radiation target volume was expanded to the contralateral neck or to the pharyngeal axis, due to suspicious lesions on imaging. The 5-year DFS, OS and RCR were 60%, 51.2%, and 80%, respectively, in the total patient population. RCR did not differ in patients treated with ipsilateral as compared to bilateral radiotherapy nor did 5-year OS and DFS. No tumors occurred in the pharyngeal axis. CONCLUSION: In this study, omitting elective treatment of the contralateral neck and pharyngeal axis did not lead to a decrease in locoregional control or survival rates when treating patients with CUP.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Primárias Desconhecidas , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Linfonodos/patologia , Metástase Linfática , Esvaziamento Cervical , Estadiamento de Neoplasias , Neoplasias Primárias Desconhecidas/radioterapia , Estudos RetrospectivosRESUMO
Background and study aims Percutaneous endoscopic gastrostomy (PEG) and percutaneous radiologic gastrostomy (PRG) are techniques used for long-term enteral feeding. Our primary aim was to analyze procedure-related and 30-day mortality and complications between PEG and PRG in relation to indications. Patients and methods A single-center retrospective analysis was performed thath included all adult patients receiving initial PEG (January 2008 until April 2016) and PRG (January 2010 until April 2016). Outcomes were mortality (procedure-related, 30-day), complications (early (≤â30 days) and late) and success rates. Results A total of 760 procedures (469 PRG and 291 PEG) were analyzed. Most common indications were head and neck cancer (HNC), cerebrovascular accident (CVA) and amyotrophic lateral sclerosis (ALS). Success rates for placement were 91.2â% for PEG and 97.1â% for PRG ( P â=â0.001). Procedure-related mortality was 1.7â% in PEG and 0.4â% in PRG ( P â=â0.113). The 30-day mortality was 10.7â% in PEG and 5.1â% in PRG ( P â=â0.481 after multivariate logistic regression) CVA was associated with higher 30-day mortality, whereas ALS, higher body weight, and prophylactic placements in HNC were associated with lower rates. Tube-related complications were less frequent in PEG, both early (2.7â% vs. 26.4â%, P â≤â0.001) and late (8.6â% vs. 31.5â%, P â≤â0.001). The percentage of major complications and infections did not differ. Conclusions With respect to procedure-related and 30-day mortality, PEG and PRG compare equally. PRG had a higher procedural success rate. Tube-related complications and pain are less frequent after PEG compared to PRG. The choice for either PEG or PRG therefore should primarily be based on local facilities and expertise.
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BACKGROUND: Evidence from observational studies of telomere length (TL) has been conflicting regarding its direction of association with cancer risk. We investigated the causal relevance of TL for lung and head and neck cancers using Mendelian Randomization (MR) and mediation analyses. METHODS: We developed a novel genetic instrument for TL in chromosome 5p15.33, using variants identified through deep-sequencing, that were genotyped in 2051 cancer-free subjects. Next, we conducted an MR analysis of lung (16 396 cases, 13 013 controls) and head and neck cancer (4415 cases, 5013 controls) using eight genetic instruments for TL. Lastly, the 5p15.33 instrument and distinct 5p15.33 lung cancer risk loci were evaluated using two-sample mediation analysis, to quantify their direct and indirect, telomere-mediated, effects. RESULTS: The multi-allelic 5p15.33 instrument explained 1.49-2.00% of TL variation in our data (p = 2.6 × 10-9). The MR analysis estimated that a 1000 base-pair increase in TL increases risk of lung cancer [odds ratio (OR) = 1.41, 95% confidence interval (CI): 1.20-1.65] and lung adenocarcinoma (OR = 1.92, 95% CI: 1.51-2.22), but not squamous lung carcinoma (OR = 1.04, 95% CI: 0.83-1.29) or head and neck cancers (OR = 0.90, 95% CI: 0.70-1.05). Mediation analysis of the 5p15.33 instrument indicated an absence of direct effects on lung cancer risk (OR = 1.00, 95% CI: 0.95-1.04). Analysis of distinct 5p15.33 susceptibility variants estimated that TL mediates up to 40% of the observed associations with lung cancer risk. CONCLUSIONS: Our findings support a causal role for long telomeres in lung cancer aetiology, particularly for adenocarcinoma, and demonstrate that telomere maintenance partially mediates the lung cancer susceptibility conferred by 5p15.33 loci.
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Adenocarcinoma de Pulmão/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Neoplasias de Cabeça e Pescoço/epidemiologia , Leucócitos/metabolismo , Neoplasias Pulmonares/epidemiologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/epidemiologia , Homeostase do Telômero/genética , Telômero/metabolismo , Idoso , Idoso de 80 Anos ou mais , Cromossomos Humanos Par 5/genética , Feminino , Humanos , Masculino , Análise da Randomização Mendeliana , Pessoa de Meia-IdadeRESUMO
BACKGROUND: The optimal technique for long-term enteral feeding has not yet been established. Both percutaneous endoscopic gastrostomy (PEG) and percutaneous radiologic gastrostomy (PRG) are widely used. Aim was to extensively review outcomes of PEG and PRG. MATERIALS AND METHODS: A systematic review using Medline, Embase, and Cochrane was performed, using standardized tools for assessing bias. Main outcomes were infectious and tube-related complications, procedure related and 30-day mortality. Pooled risk differences (RDs) with corresponding 95% confidence intervals (95% CIs) were calculated using random effects. Arcsine transformations were applied. RESULTS: In total, 344 studies were identified, of which 16 were included, reporting on 934 PEGs and 1093 PRGs. No differences were found for infectious complications [RD, 0.03 (-0.05 to 0.11)], procedure-related mortality [RD, 0.01 (-0.04 to 0.06)], or 30-day mortality [RD, 0.06 (-0.01 to 0.13)]. Tube-related complications were higher in PRG [RD, 0.16 (0.06-0.26)]. Subgroup analysis was performed for head and neck cancer (HNC) and motor neuron disease. In HNC, this revealed significantly lower tube-related complications and procedure-related mortality after PEG. In motor neuron disease, no differences were seen. The level of evidence appears sufficient considering the low degree of heterogeneity. CONCLUSIONS: No differences were found with regard to mortality or infectious complications. PEG showed lower risk of tube-related complications. Subgroup analysis revealed PEG to be favorable in HNC based on lower rates of procedure-related mortality and tube-related complications. Local experience and availability should be taken into account in the decision process.
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Nutrição Enteral/métodos , Gastrostomia/métodos , Complicações Pós-Operatórias/etiologia , Gastrostomia/efeitos adversos , Gastrostomia/mortalidade , Neoplasias de Cabeça e Pescoço/complicações , Humanos , Doença dos Neurônios Motores/complicações , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/mortalidadeRESUMO
Background: Most pathogenic mutations in the BRCA2 gene carry a high risk of hereditary breast and ovarian cancer (HBOC). However, a stop-gain mutation, K3326* (rs11571833), confers risk of lung cancer and cancers of the upper-aero-digestive tract but only a modest risk of breast or ovarian cancer. The Icelandic population provides an opportunity for comprehensive characterization of the cancer risk profiles of K3326* and HBOC mutations because a single mutation, BRCA2 999del5, is responsible for almost all BRCA2-related HBOC in the population. Methods: Genotype information on 43 641 cancer patients and 370 971 control subjects from Iceland, the Netherlands, and the United States was used to assess the cancer risk profiles of K3326* and BRCA2 999del5. BRCA2 expression was assessed using RNAseq data from blood (n = 2233), as well as 52 tissues reported in the GTEx database. Results: The cancer risks associated with K3326* are fundamentally different from those associated with 999del5. We report for the first time an association between K3326* and small cell lung cancer (odds ratio [OR] = 2.06, 95% confidence interval [CI] = 1.35 to 3.16) and squamous cell carcinoma of the skin (OR = 1.69, 95% CI = 1.26 to 2.26). Individuals homozygous for K3326* reach old age and have children. Unlike BRCA2 999del5, the K3326* allele does not affect the level of BRCA2 transcripts, and the allele is expressed to the same extent as the wild-type allele. Conclusions: K3326* associates primarily with cancers that have strong environmental genotoxic risk factors. Expression of the K3326* allele suggests that a variant protein may be made that retains the DNA repair capabilities important to hormone-responsive tissues but may be less efficient in responding to genotoxic stress.
Assuntos
Carcinoma de Células Escamosas/genética , Genes BRCA2 , Predisposição Genética para Doença , Neoplasias Pulmonares/genética , Neoplasias Cutâneas/genética , Carcinoma de Pequenas Células do Pulmão/genética , Alelos , Genótipo , Humanos , Islândia/epidemiologia , Mutação , Países Baixos/epidemiologia , Razão de Chances , Polimorfismo de Nucleotídeo Único , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Incidences of pharyngocutaneous fistulization (PCF) after total laryngectomy (TL) reported in the literature vary widely, ranging from 2.6 to 65.5%. Comparison between different centers might identify risk factors, but also might enable improvements in quality of care. To enable this on a national level, an audit in the 8 principle Dutch Head and Neck Centers (DHNC) was initiated. METHODS: A retrospective chart review of all 324 patients undergoing laryngectomy in a 2-year (2012 and 2013) period was performed. Overall PCF%, PCF% per center and factors predictive for PCF were identified. Furthermore, a prognostic model predicting the PCF% per center was developed. To provide additional data, a survey among the head and neck surgeons of the participating centers was carried out. RESULTS: Overall PCF% was 25.9. The multivariable prediction model revealed that previous treatment with (chemo)radiotherapy in combination with a long interval between primary treatment and TL, previous tracheotomy, near total pharyngectomy, neck dissection, and BMI < 18 were the best predictors for PCF. Early oral intake did not influence PCF rate. PCF% varied quite widely between centers, but for a large extend this could be explained with the prediction model. PCF performance rate (difference between the PCF% and the predicted PCF%) per DHNC, though, shows that not all differences are explained by factors established in the prediction model. However, these factors explain enough of the differences that, compensating for these factors, hospital is no longer independently predictive for PCF. CONCLUSIONS: This nationwide audit has provided valid comparative PCF data confirming the known risk factors from the literature which are important for counseling on PCF risks. Data show that variations in PCF% in the DHNCs (in part) are explainable by the variations in these predictive factors. Since elective neck dissection is a major risk factor for PCF, it only should be performed on well funded indication.
Assuntos
Fístula Cutânea/etiologia , Laringectomia , Doenças Faríngeas/etiologia , Complicações Pós-Operatórias/etiologia , Fístula do Sistema Respiratório/etiologia , Adulto , Idoso , Fístula Cutânea/epidemiologia , Feminino , Humanos , Incidência , Masculino , Auditoria Médica , Pessoa de Meia-Idade , Esvaziamento Cervical/efeitos adversos , Avaliação de Resultados em Cuidados de Saúde , Doenças Faríngeas/epidemiologia , Faringectomia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Fístula do Sistema Respiratório/epidemiologia , Estudos Retrospectivos , Fatores de RiscoRESUMO
PURPOSE: This study aimed to assess patient-reported levels of physical activity (PA) and its associations with health-related quality of life (HRQoL) adjusted for important demographic, lifestyle-related, and clinical factors, among head and neck (HNC) survivors. METHODS: This cross-sectional study included 116 HNC survivors. PA was assessed with the Physical Activity Scale for the Elderly (PASE) and HRQoL with the EORTC-QLQ-C30 and EORTC-HN35. Associations were studied using univariable and multivariable regression analyses. RESULTS: Median PASE score was 100.3 (interquartile range 65.1;170.8) of which 54% were household, 34% leisure-time, and 12% occupational activities. Younger HNC survivors had higher levels of PA. Higher PA was significantly associated with higher global QoL (p < 0.05). Findings for physical function, role function, social function, fatigue, and pain were in line, but not statistically significant (0.05 ≤ p < 0.10). CONCLUSIONS: Among HNC survivors, a large proportion of PA consists of household activities. Younger HNC survivors had higher PA levels, and higher PA levels were associated with higher HRQoL.
Assuntos
Sobreviventes de Câncer/psicologia , Exercício Físico/fisiologia , Exercício Físico/psicologia , Neoplasias de Cabeça e Pescoço/fisiopatologia , Neoplasias de Cabeça e Pescoço/psicologia , Estudos Transversais , Feminino , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Análise de Regressão , AutorrelatoRESUMO
We conducted a genome-wide association study of oral cavity and pharyngeal cancer in 6,034 cases and 6,585 controls from Europe, North America and South America. We detected eight significantly associated loci (P < 5 × 10-8), seven of which are new for these cancer sites. Oral and pharyngeal cancers combined were associated with loci at 6p21.32 (rs3828805, HLA-DQB1), 10q26.13 (rs201982221, LHPP) and 11p15.4 (rs1453414, OR52N2-TRIM5). Oral cancer was associated with two new regions, 2p23.3 (rs6547741, GPN1) and 9q34.12 (rs928674, LAMC3), and with known cancer-related loci-9p21.3 (rs8181047, CDKN2B-AS1) and 5p15.33 (rs10462706, CLPTM1L). Oropharyngeal cancer associations were limited to the human leukocyte antigen (HLA) region, and classical HLA allele imputation showed a protective association with the class II haplotype HLA-DRB1*1301-HLA-DQA1*0103-HLA-DQB1*0603 (odds ratio (OR) = 0.59, P = 2.7 × 10-9). Stratified analyses on a subgroup of oropharyngeal cases with information available on human papillomavirus (HPV) status indicated that this association was considerably stronger in HPV-positive (OR = 0.23, P = 1.6 × 10-6) than in HPV-negative (OR = 0.75, P = 0.16) cancers.
Assuntos
Marcadores Genéticos/genética , Predisposição Genética para Doença , Variação Genética/genética , Estudo de Associação Genômica Ampla , Neoplasias Bucais/genética , Infecções por Papillomavirus/genética , Neoplasias Faríngeas/genética , Idoso , Estudos de Casos e Controles , Feminino , Antígenos HLA , Haplótipos/genética , Humanos , Masculino , Pessoa de Meia-Idade , Boca/metabolismo , Boca/patologia , Boca/virologia , Neoplasias Bucais/virologia , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/virologia , Neoplasias Faríngeas/virologiaRESUMO
Anterior neck masses in young children can be a diagnostic challenge for otolaryngologists and radiologists. We present a rare case of herniation of normal mediastinal thymus in a four-year-old girl. Additional medical features as an inguinal hernia and trochlear nerve paresis raised the question whether there is a causal relationship or an association. A connective tissue disorder could not be diagnosed as possible causal factor to the abnormal movement of the mediastinal thymus. Awareness and recognition of this benign phenomenon is important in order to avoid unnecessary biopsy or surgery. Diagnosis can be confirmed by ultrasonography. Magnetic Resonance Imaging might be valuable in order to obtain more information about the extension of the mass.
Assuntos
Hérnia/diagnóstico , Doenças do Mediastino/diagnóstico , Timo/patologia , Biópsia , Pré-Escolar , Diagnóstico Diferencial , Feminino , Humanos , Imageamento por Ressonância Magnética , PescoçoRESUMO
BACKGROUND: Warthin's tumors of the parotid gland are associated with smoking, whereas pleomorphic adenomas are not. Genetic polymorphisms in biotransformation enzymes, involved in detoxification of toxins and carcinogens in cigarette smoke, might modify the corresponding enzyme activity and influence detoxifying capacity. We hypothesize that these genetic polymorphisms may influence the individual risk for Warthin's tumor, but not for pleomorphic adenomas. METHODS: Blood from 146 patients with benign parotid gland tumors and 437 controls were investigated for polymorphisms in several biotransformation enzymes. Based on these polymorphisms, patients and controls were divided according to predicted enzyme activity (low, intermediate, and high). RESULTS: Prevalence of predicted intermediate and high activity UGT1A7 and UGT1A6 genotypes was significantly higher in the patients with Warthin's tumors, but not in patients with pleomorphic adenomas, compared with healthy controls. CONCLUSION: Predicted intermediate and high activity UGT1A7 and UGT1A6 genotypes are associated with an increased risk for Warthin's tumor. © 2015 Wiley Periodicals, Inc. Head Neck 38: E717-E723, 2016.