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1.
Eur Arch Otorhinolaryngol ; 276(8): 2311-2318, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31134358

RESUMEN

PURPOSE: Gold-standard for defect reconstruction in the head and neck region is the radial free forearm flap (RFFF). The supraclavicular artery island flap (SCAIF) gained popularity due to its versatility. Our objective was to compare functional advantages between both modalities. METHODS: A retrospective analysis of 24 consecutive cases with advanced-stage squamous cell cancer of the oral cavity and oropharynx after cancer defect reconstruction with two modalities (12 SCAIF; 12 RFFF) was conducted. Patients completed the European Organization for Research and Treatment of Cancer (EORTC) questionnaires, Quality of Life Questionnaire-Core 30-questions (QLQ-C30) and Quality of Life Questionnaire-Core 30 Head and Neck 35-questions (QLQ-H&N35). RESULTS: Mean follow-up was 22.2 ± 9.5 months. Comparison of quality of life (QOL) showed significant differences only in speech and problems with the senses in favor of the SCAIF. CONCLUSION: Patients report satisfactory QOL results after oncologic surgery and reconstruction with preliminary no significant differences in most aspects comparing the two modalities. Therefore, the SCAIF appears as a viable alternative to the gold standard, the RFFF.


Asunto(s)
Carcinoma de Células Escamosas/cirugía , Neoplasias de Cabeza y Cuello/cirugía , Procedimientos de Cirugía Plástica/métodos , Calidad de Vida , Colgajos Quirúrgicos/irrigación sanguínea , Anciano , Femenino , Antebrazo/cirugía , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Encuestas y Cuestionarios
2.
J Oral Maxillofac Surg ; 75(10): 2261-2269, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28342884

RESUMEN

PURPOSE: To evaluate whether the pedicled supraclavicular artery island flap (SCAIF) is a sufficient alternative to the fasciocutaneous radial forearm free flap (RFFF) for oral reconstruction in cancer surgery. PATIENTS AND METHODS: The authors designed and implemented a retrospective cohort study composed of all consecutive patients who underwent head and neck reconstruction after cancer surgery at their tertiary university hospital from 2013 to 2016. Demographics and peri- and postoperative information were recorded and statistically analyzed. RESULTS: Of 83 patients who underwent head and neck reconstruction after cancer, 50 were identified as having stage III or IV squamous cell carcinoma of the oral cavity and oropharynx and underwent surgery and reconstruction with the SCAIF (n = 25) or the RFFF (n = 25). Total surgery time (411.0 vs 576.4 minutes; P < .001), flap elevation time (39.00 vs 93.78 minutes; P < .001), need for intensive care observation (32 vs 96%; P < .05), and rate of tracheotomy (64 vs 88%; P < .05) were significantly lower in the SCAIF group. There was no statistical difference in the postoperative complication rate or postoperative functional swallowing ability between the 2 groups. Total perioperative costs were significantly lower in patients who underwent reconstruction with the SCAIF (2,621.15 vs 4,453.77€; P < .01). CONCLUSION: The results of this study suggest that the SCAIF is a straightforward and reliable flap with shorter operative times and comparable outcomes compared with the RFFF.


Asunto(s)
Neoplasias de la Boca/cirugía , Procedimientos de Cirugía Plástica/métodos , Colgajos Quirúrgicos/irrigación sanguínea , Anciano , Arterias , Estudios de Cohortes , Femenino , Antebrazo/cirugía , Colgajos Tisulares Libres , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
3.
Eur Arch Otorhinolaryngol ; 274(4): 1997-2004, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28028607

RESUMEN

For the treatment of T1b glottic carcinoma, different treatment options, such as transoral laser microsurgery, open surgical techniques, and primary radiotherapy, are under discussion. In this context, the aim of the present study was to describe oncologic results and complication rates of transoral laser microsurgery in treatment of T1b glottic carcinoma. This is a retrospective unicenter chart review of patients treated at an academic tertiary referral center between 1986 and 2006. Fifty-one previously untreated T1b cases were exclusively treated by transoral laser microsurgery and included into this study, 47 were male, and 4 were female. The main outcome measures included local control rate and complications, overall, disease specific, and recurrence-free survival. The median follow-up period was 98 months. The 5-year local control rate was 90.2%; larynx preservation rate was 92.2%. No intra- or postoperative complications, such as wound infections, postoperative bleeding, hematoma, edema, and fistula development, were observed. A single patient required revision surgery due to synechia. Five-year survival rates were: overall 84.7%, disease specific 97.7%, and recurrence free 72.4%. Our data support the conclusion that transoral laser microsurgery is a considerable treatment option in T1b glottic carcinoma. The oncologic outcome was at least comparable to other treatment options, while the perioperative morbidity and complication rate were lower.


Asunto(s)
Carcinoma de Células Escamosas , Glotis , Neoplasias Laríngeas , Terapia por Láser , Recurrencia Local de Neoplasia/cirugía , Complicaciones Posoperatorias , Anciano , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/cirugía , Femenino , Alemania , Glotis/patología , Glotis/cirugía , Humanos , Neoplasias Laríngeas/patología , Neoplasias Laríngeas/cirugía , Terapia por Láser/efectos adversos , Terapia por Láser/métodos , Masculino , Microcirugia/efectos adversos , Microcirugia/métodos , Persona de Mediana Edad , Boca/cirugía , Estadificación de Neoplasias , Evaluación de Resultado en la Atención de Salud , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/cirugía , Reoperación/métodos , Estudios Retrospectivos
4.
Eur Arch Otorhinolaryngol ; 273(6): 1533-41, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25864181

RESUMEN

This study analyzed the efficacy of transoral laser microsurgery and postoperative (chemo) radiotherapy (CRT) for head and neck squamous cell carcinoma. Between 1987 and 2007, 318 patients with pN2 neck disease were included. Seventy-three patients received laser resection and neck dissection alone, 154 postoperative radiotherapy, and 91 postoperative (C)RT. Mean follow-up was 58.2 ± 51.2 months, and locoregional control was significantly better after postoperative (C)RT (surgery alone: 42 %, radiotherapy: 57 %, CRT: 59 %; p < 0.01). Postoperative (C)RT did not have a significant impact on disease-specific survival (DSS) (surgery alone: 55 %, radiotherapy alone: 60 %, CRT: 64 %; p = 0.36). Fifty-seven patients (17.92 %) developed distant metastases, and 39 patients (12.26 %) presented with secondary malignancies, with no significant differences found between the treatment groups. Postoperative (C)RT significantly improved locoregional control, but had no significant effect on DSS because of high rates of secondary malignancies and distant metastases. Reduced radicality in combination with an effective screening might improve prognosis and quality of life of these patients.


Asunto(s)
Carcinoma de Células Escamosas/terapia , Quimioradioterapia/métodos , Neoplasias de Cabeza y Cuello/terapia , Terapia por Láser/métodos , Microcirugia/métodos , Disección del Cuello/métodos , Recurrencia Local de Neoplasia/terapia , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/secundario , Femenino , Neoplasias de Cabeza y Cuello/patología , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Pronóstico , Calidad de Vida , Estudios Retrospectivos , Resultado del Tratamiento
5.
Eur Arch Otorhinolaryngol ; 270(12): 3177-82, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23632872

RESUMEN

Recombinant allergen diagnostics have become increasingly important in daily allergological routine, made possible by inroads into the understanding of major and minor allergens accomplished within the last decade. Recombinant allergen diagnostics will, however, only provide correct diagnoses when sufficient knowledge of the regional IgE reactivity profile to a specific allergen source is available. A variety of studies in different European countries revealed reactivity profiles, where a sensitization to house dust mite could be recognized in more than 97 % of cases in which Der p1 and Der p2 were measured. The aim of this study was to investigate the IgE reactivity profiles of house dust mite allergic patients in southern Germany. Sera of house dust mite allergic patients (positive intranasal provocation) were screened for IgE antibodies against commercially available D pter., nDer p1, rDer p2 and rDer p10. IgE antibodies against D pter. could be found in 98 out of 98 sera (100 %). Seventy-five patients (76.5 %) reacted to nDer p1. In 72 patients (73.4 %), IgE antibodies against rDer p2 could be found, while IgE antibodies against rDer p10 were present in only 4 patients (4.1 %). Seventeen patients (17.3 %) had no IgE antibodies against nDer p1, rDer p2 and nDer p10, but displayed reactions to D pter. Knowledge of IgE regional reactivity profiles is necessary when using recombinant allergen diagnostics. In the case of our house dust mite allergic patients 17 would have remained undiagnosed based on a diagnostic method utilizing only the two major allergens nDerp1 and rDerp2.


Asunto(s)
Antígenos Dermatofagoides/inmunología , Hipersensibilidad/inmunología , Inmunoglobulina E/inmunología , Pyroglyphidae/inmunología , Adolescente , Adulto , Anciano , Animales , Niño , Femenino , Alemania , Humanos , Técnicas para Inmunoenzimas , Masculino , Persona de Mediana Edad , Pruebas Cutáneas
6.
Cancers (Basel) ; 14(10)2022 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-35626037

RESUMEN

Cold atmospheric plasma (CAP) has demonstrated promising anti-cancer effects in numerous in vitro and in vivo studies. Despite their relevance for the treatment of solid tumors, effects of CAP on tumor vasculature and microcirculation have only rarely been investigated. Here, we report the reduction of vessel density and an increase in vascular permeability and tumor cell apoptosis after CAP application. Solid tumors in the chorioallantoic membrane of chicken embryos were treated with CAP and evaluated with respect to effects of CAP on embryo survival, tumor size, and tumor morphology. Furthermore, intratumoral blood vessel density, apoptotic cell death and the tumor-associated microcirculation were investigated and compared to sham treatment. Treatment with CAP significantly reduced intratumoral vessel density while increasing the rate of intratumoral apoptosis in solid tumors. Furthermore, CAP treatment increased vascular permeability and attenuated the microcirculation by causing vessel occlusions in the tumor-associated vasculature. These effects point out the potential of CAP as a promising and yet underrated therapeutic modality for addressing the tumor vasculature in the treatment of solid tumors.

7.
Head Face Med ; 18(1): 21, 2022 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-35768853

RESUMEN

BACKGROUND: The aim of the present study was to examine the cytostatic effects of cold atmospheric plasma (CAP) on different head and neck squamous carcinoma (HNSCC) cell lines either in isolation or in combination with low dose cisplatin. The effect of CAP treatment was investigated by using three different HNSCC cell lines (chemo-resistant Cal 27, chemo-sensitive FaDu and OSC 19). MATERIALS AND METHOD: Cell lines were exposed to CAP treatment for 30, 60, 90, 120 and 180 s (s). Cisplatin was added concurrently (cc) or 24 h after CAP application (cs). Cell viability, DNA damage and apoptosis was evaluated by dye exclusion, MTT, alkaline microgel electrophoresis assay and Annexin V-Fit-C/PI respectively. RESULTS: In all cell lines, 120 s of CAP exposure resulted in a significant reduction of cell viability. DNA damage significantly increased after 60 s. Combined treatment of cells with CAP and low dose cisplatin showed additive effects. A possible sensitivity to cisplatin could be restored in Cal 27 cells by CAP application. CONCLUSION: CAP shows strong cytostatic effects in HNSCC cell lines that can be increased by concurrent cisplatin treatment, suggesting that CAP may enhance the therapeutic efficacy of low dose cisplatin.


Asunto(s)
Carcinoma de Células Escamosas , Citostáticos , Neoplasias de Cabeza y Cuello , Gases em Plasma , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/genética , Línea Celular Tumoral , Cisplatino/farmacología , Cisplatino/uso terapéutico , Citostáticos/uso terapéutico , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Humanos , Gases em Plasma/farmacología , Gases em Plasma/uso terapéutico , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico
8.
Am J Otolaryngol ; 32(1): 19-23, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-20015810

RESUMEN

OBJECTIVES: Studies suggest that hypercholesterolemia promotes the development of inner ear disorders such as tinnitus. However, the underlying pathomechanisms are still not clearly defined. METHODS: A retrospective study was performed to assess whether a reduction of serum cholesterol by 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors may result in a relief of subacute tinnitus. Remission rates of 58 patients were investigated after 4 months of treatment with simvastatin (40 mg). Results were compared to treatment with Ginkgo biloba (120 mg; n = 36) as control group. Differences between tinnitus score at the day of first treatment and after 4 months were used as main outcome measure. RESULTS: After treatment with simvastatin or G biloba, tinnitus score decreased from 41.3 ± 10.4 to 37.4 ± 17.3 and from 44.7 ± 11.2 to 41.2 ± 8.7, respectively. However, independently of the treatment regimen, differences of tinnitus scores were considered not significant. CONCLUSIONS: After administration of simvastatin over 4 months, this retrospective study has shown no significant efficacy in treatment of subacute tinnitus. For a more conclusive answer, further prospective, double-blind, and placebo-controlled studies with a larger number of patients are needed.


Asunto(s)
Ginkgo biloba , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Hipercolesterolemia/tratamiento farmacológico , Fitoterapia/métodos , Preparaciones de Plantas/uso terapéutico , Simvastatina/uso terapéutico , Acúfeno/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Audiometría de Tonos Puros , Femenino , Humanos , Hipercolesterolemia/complicaciones , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Acúfeno/etiología , Resultado del Tratamiento
9.
Mutat Res ; 677(1-2): 42-5, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19539778

RESUMEN

Epidermal Growth Factor Receptor (EGFR) signalling is particularly important in the biology of the vast majority of solid human malignancies. EGFR is over-expressed in up to 90-100% of head-and-neck squamous cell carcinomas (HNSCC), and increased expression of EGFR and its ligand Transforming Growth Factor-alpha (TGF-alpha) is not limited to malignant cells, but also detected in histologically normal mucosa of HNSCC patients, supporting the hypothesis of field carcinogenesis. Permanent EGFR activation via an autocrine stimulatory pathway is thought to be a major factor forcing pre-neoplastic tissue towards malignancy. Our study evaluates the impact of stimulation by TGF-alpha on carcinogen-induced and oxidative DNA damage in mucosa tissue cultures of macroscopically normal biopsies from tumour patients and controls. Effects of TGF-alpha on DNA-repair capacity were investigated. To assess DNA fragmentation, alkaline single-cell gel electrophoresis (comet assay) was used. Stimulation of cultures during 24 h with TGF-alpha decreased benzo(a)pyrene diolepoxide (BPDE)-induced DNA damage by 36% in the tumour group (p < 0.001) and by 7% in controls (n = 30). No statistically significant impact on oxidatively induced DNA fragmentation in both groups (n = 15 and 20, respectively), or DNA repair could be shown n (n = 6). The exact mechanism by which TGF-alpha stimulation reduces BPDE-induced DNA fragmentation remains unclear. It was shown in clinical studies, that EGFR targeting has synergistic effects with chemotherapy in HNSCC and reverses chemo-resistance of epithelial tumours, which was shown to be the consequence of altered expression of multidrug resistance (mdr) efflux pumps. EGFR downstream signalling regulates the transcription of MDR1 (p-glycoproteine) and glutathione homeostasis. BPDE is a substrate of mdr1 and is detoxified by glutathione conjugation. However, our results show a strong DNA-stabilizing effect of stimulation by TGF-alpha in mucosa tissue cultures of tumour patients and may therefore be seen as a physiological response to continued carcinogenic impact on the epithelium of the upper aerodigestive tract.


Asunto(s)
Carcinoma de Células Escamosas/genética , Daño del ADN/efectos de los fármacos , Neoplasias de Cabeza y Cuello/genética , Factor de Crecimiento Transformador alfa/farmacología , 7,8-Dihidro-7,8-dihidroxibenzo(a)pireno 9,10-óxido/toxicidad , Carcinógenos , Fragmentación del ADN/efectos de los fármacos , Reparación del ADN , Humanos , Peróxido de Hidrógeno/farmacología , Mucosa Bucal/ultraestructura , Técnicas de Cultivo de Órganos , Mucosa Respiratoria/ultraestructura
10.
Auris Nasus Larynx ; 46(2): 294-301, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30098846

RESUMEN

OBJECTIVE: Ear, nose and throat infections are among the most common reasons for absence from work. They are usually caused by various bacteria like Haemophilus influenzae, Staphylococcus aureus, Streptococcus pneumoniae and Streptococcus pyogenes. Cold atmospheric plasma (CAP) can effectively eliminate even multi-resistant bacteria and has no cytotoxic or mutagenic effects on the mucosa when applied for less than 60s. Aim of the study was to evaluate the effects of CAP on common ENT bacteria and on the mucosa of the upper aerodigestive tract. METHODS: The bactericidal effects of CAP against the bacteria most commonly causing ENT infections were investigated using the colony-forming units assay (CFU) on a Müller-Hinton agar plate after applying CAP for 30, 60, 90 and 120s. To evaluate the interaction of CAP with mucosal cells, 3D mini organ cultures were treated for up to 180s, after which cell viability and necrosis induction were evaluated. RESULTS: Treatment with CAP for 60s or longer induced at least a 3-log10 reduction in the bacterial load (> 99.9%). Treatment times shorter than 60s had only slight cytotoxic effects on cell viability and necrosis whereas treatment times above 60s showed a fast increase of cytotoxic side effects. CONCLUSION: CAP exhibited strong bactericidal effects on the most common ENT pathogens. Treatment times of up to 60s showed only minimal adverse reactions in healthy mucosa. CAP could be a promising new therapeutic modality for ENT infections.


Asunto(s)
Haemophilus influenzae/efectos de los fármacos , Otitis/microbiología , Gases em Plasma/farmacología , Mucosa Respiratoria/efectos de los fármacos , Infecciones del Sistema Respiratorio/microbiología , Staphylococcus aureus/efectos de los fármacos , Streptococcus pneumoniae/efectos de los fármacos , Streptococcus pyogenes/efectos de los fármacos , Adulto , Supervivencia Celular/efectos de los fármacos , Recuento de Colonia Microbiana , Femenino , Humanos , Masculino , Persona de Mediana Edad , Necrosis , Técnicas de Cultivo de Órganos , Orofaringe , Faringitis/microbiología , Mucosa Respiratoria/patología , Rinitis/microbiología , Adulto Joven
11.
Otolaryngol Head Neck Surg ; 158(5): 878-881, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29293403

RESUMEN

Perineural invasion (PNI) is an underrecognized path of cancer spread, and its causes and mechanisms are poorly understood. Recent research indicates a mutual attraction of neuronal and cancer cells, largely dependent on neurotrophic factors and their receptors. Interestingly, the release of neurotrophic factors occurs upon cigarette smoke/nicotine exposure in a dose-dependent manner, and serum levels correlate with current smoking, number of smoking years, and smoking severity. Among cell types capable of neurotrophic factors secretion are lung and oral fibroblasts. In our study of 178 patients with head and neck squamous cell carcinoma, tumors of current and former smokers showed PNI significantly more often than tumors of never smokers. Moreover, PNI was a marker for aggressive tumor growth. Surprisingly, PNI was more significant for survival than p16 status. Our study warrants further research on PNI in head and neck squamous cell carcinoma with special emphasis on the impact of tobacco consumption to identify suitable candidates for therapeutic interventions.


Asunto(s)
Invasividad Neoplásica/patología , Nervios Periféricos/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Uso de Tabaco/efectos adversos , Supervivencia sin Enfermedad , Humanos , Estudios Retrospectivos , Carcinoma de Células Escamosas de Cabeza y Cuello/mortalidad , Tasa de Supervivencia
12.
Plast Reconstr Surg Glob Open ; 6(4): e1711, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29876164

RESUMEN

BACKGROUND: The pedicled supraclavicular artery island flap (SCAIF) for reconstruction of the head and neck has been shown to be a pliable alternative to established pedicled flaps, such as the pectoralis major myocutaneous flap. Because there are limited published data regarding shoulder morbidity after SCAIF procedure, we aimed to investigate it with 2 established questionnaires for the upper extremity [Constant-Murley score and Disabilities of the Arm, Shoulder and Hand Outcome Measure (DASH) score]. METHODS: The authors designed and implemented a retrospective cohort study of patients who received a defect reconstruction by SCAIF. Analyzed parameters were demographics, comorbidities, donor-site morbidity and shoulder morbidity in terms of range of motion, pain, strength, and daily activities evaluated and compared between the donor site and contralateral arm. RESULTS: Of the 61 consecutively performed head and neck reconstructions with SCAIF, 20 met inclusion criteria (curative intended treatment, head and neck squamous cell cancer, follow-up time more than 4 months). Mean follow-up was 17.3 months (±10.4 months) ranging from 4-35 months. Donor-site complication rate was low with 5% major (surgical revision) and 30% minor complications (conservative management). Overall Constant-Murley-Score (P = 0.334), pain (P = 0.150), overall range of motion (P = 0.861), and strength of the extremity (P = 0.638) of the shoulder receiving a SCAIF showed no significant differences to the contralateral extremity. Mean of Disabilities of the Arm, Shoulder and Hand Outcome Measure score was 32.5 (±28.6). CONCLUSION: The results of the present study suggest very low shoulder morbidity in patients after SCAIF procedure with no significant functional impairment of the donor shoulder compared with the contralateral side.

13.
Head Neck ; 40(5): 963-972, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29356187

RESUMEN

BACKGROUND: The surgeon's evaluation of resection status based on frozen section analysis during operation and pathological examination of resected specimens often differ. For this study, we recapitulated the surgeon's perspective during an operation, accordingly classified the evaluation of margins by the surgeon, and analyzed its impact on the outcome compared with the pathological results. METHODS: This was a retrospective analysis. As data sources, paper-based and digital patient files, as well as the Munich Cancer Registry database were used. RESULTS: Three hundred ninety-six cases were included in this analysis. Only the evaluation of margins by the surgeon influenced local control, and the pathological results influenced disease-free survival (DFS). Surprisingly, margins of >5 mm of normal tissue to cancer growth led to local control and overall survival (OS) significantly worse than 1 to 5-mm resections. CONCLUSION: The evaluation of margins by the surgeon is of significant importance for local control and OS. It is largely based on frozen section analysis, which, therefore, should be used whenever possible.


Asunto(s)
Márgenes de Escisión , Recurrencia Local de Neoplasia/epidemiología , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Secciones por Congelación , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Estudios Retrospectivos , Carcinoma de Células Escamosas de Cabeza y Cuello/mortalidad , Tasa de Supervivencia , Adulto Joven
15.
J Vis Exp ; (134)2018 04 20.
Artículo en Inglés | MEDLINE | ID: mdl-29733308

RESUMEN

Current treatment options for advanced and recurrent head and neck squamous cell carcinoma (HNSCC) enclose radiation and chemo-radiation approaches with or without surgery. While platinum-based chemotherapy regimens currently represent the gold standard in terms of efficacy and are given in the vast majority of cases, new chemotherapy regimens, namely immunotherapy are emerging. However, the response rates and therapy resistance mechanisms for either chemo regimen are hard to predict and remain insufficiently understood. Broad variations of chemo and radiation resistance mechanisms are known to date. This study describes the development of a standardized, high-throughput in vitro assay to assess HNSCC cell line's response to various therapy regimens, and hopefully on primary cells from individual patients as a future tool for personalized tumor therapy. The assay is designed to being integrated into the quality-controlled standard algorithm for HNSCC patients at our tertiary care center; however, this will be subject of future studies. Technical feasibility looks promising for primary cells from tumor biopsies from actual patients. Specimens are then transferred into the laboratory. Biopsies are mechanically separated followed by enzymatic digestion. Cells are then cultured in ultra-low adhesion cell culture vials that promote the reproducible, standardized and spontaneous formation of three-dimensional, spheroid-shaped cell conglomerates. Spheroids are then ready to be exposed to chemo-radiation protocols and immunotherapy protocols as needed. The final cell viability and spheroid size are indicators of therapy susceptibility and therefore could be drawn into consideration in future to assess the patients' likely therapy response. This model could be a valuable, cost-efficient tool towards personalized therapy for head and neck cancer.


Asunto(s)
Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/terapia , Técnicas de Cultivo de Célula/métodos , Neoplasias de Cabeza y Cuello/diagnóstico , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/terapia , Humanos , Medicina de Precisión , Carcinoma de Células Escamosas de Cabeza y Cuello
16.
Head Neck ; 39(8): 1631-1638, 2017 08.
Artículo en Inglés | MEDLINE | ID: mdl-28474378

RESUMEN

BACKGROUND: The oncologic and functional outcome of transoral laser microsurgery (TLM) for primary treatment of hypopharyngeal cancer was examined in a multimodal treatment concept. METHODS: Two hundred eleven patients with squamous cell carcinoma (SCC) of the hypopharynx (pT1-4a, pN0-2, M0) were treated by TLM +/- neck dissection (88%) +/- (chemo)radiotherapy ([C]RT; 51%). The majority of cases were advanced stages III and IVa (85%). RESULTS: The 5-year Kaplan-Meier estimates for local control after TLM were pT category-related 88.1%, 74.8%, 77.3%, and 61.8% for pT1-4a tumors. The 5-year estimates of overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) for early stages I and II were 68.2%, 96.7%, and 74.6%, respectively; for stage III they were 65.9%, 83.8%, and 56.4%, respectively; and the rates for stage IVa were 44.5%, 60.7%, and 50.3%, respectively. Overall, 95.7% of the patients maintained regular oral nutrition without feeding tube dependency. CONCLUSION: Primary TLM in multimodal concepts of treatment (+/- neck dissection, +/- [C]RT) offers favorable oncologic results as compared with other therapeutic regimes.


Asunto(s)
Carcinoma de Células Escamosas/cirugía , Neoplasias Hipofaríngeas/cirugía , Terapia por Láser/métodos , Microcirugia , Disección del Cuello , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/terapia , Quimioradioterapia Adyuvante , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Humanos , Neoplasias Hipofaríngeas/terapia , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
17.
Anticancer Res ; 37(5): 2201-2210, 2017 05.
Artículo en Inglés | MEDLINE | ID: mdl-28476783

RESUMEN

BACKGROUND/AIM: Chemo-radiation currently serves as first-line therapy of advanced and recurrent head and neck cancer, while new chemotherapy regimens are emerging. However, response rates to any treatment are difficult to predict and underlie broad variation. This study shows the development of a standardized, high-throughput in vitro assay to assess patients' individual response to therapy regimens as a future tool for personalized tumor therapy. MATERIALS AND METHODS: Viability and proliferation analyses after chemo +/- radiation treatment of single spheroids (low adhesion plates/Hanging Drop (HD)) were generated from head and neck squamous cell carcinoma (HNSCC) cell lines and primary human cells from fresh tumor specimens. RESULTS: All cell lines showed reliable growth in all cell culture methods. The spheroids showed significant delay of growth and/or necrosis compared to control groups when exposed to current standard chemotherapeutic regimens. Single 3D spheroids ready for therapy susceptibility testing could be generated from actual tumor specimens after enzymatic and mechanical separation. CONCLUSION: In its current form, this single spheroid-based in vitro assay was able to test individual therapy susceptibility to current standard therapy regimens or, potentially, for testing new targeted drugs in HNSCC treatment. With recent discoveries regarding tumor heterogeneity and individual mutation status, a reliable assay is a prerequisite for personalized therapy in head and neck cancer.


Asunto(s)
Ensayos de Selección de Medicamentos Antitumorales , Neoplasias de Cabeza y Cuello/terapia , Esferoides Celulares , Antineoplásicos/farmacología , Técnicas de Cultivo de Célula , Línea Celular Tumoral , Quimioradioterapia , Descubrimiento de Drogas , Humanos , Medicina de Precisión , Esferoides Celulares/efectos de los fármacos , Esferoides Celulares/efectos de la radiación , Células Tumorales Cultivadas
18.
J Environ Pathol Toxicol Oncol ; 35(4): 343-354, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27992314

RESUMEN

The popularity of electronic cigarettes (ECs) is rapidly growing and ECs are claimed to be an uncritically regarded alternative to conventional cigarettes. The mucosal tissue of the upper aerodigestive tract (UADT) is the first contact organ for xenobiotics such as liquids of ECs. The aim of this study is to investigate the bimolecular effects of e-liquids on human pharyngeal tissue cultures to evaluate whether e-liquids and their components present a risk factor for head and neck squamous cell carcinoma. Fresh tissue samples of healthy oropharyngeal mucosa were assembled into mucosal tissue cultures. Two fruit-flavored liquids (FLs), one tobacco-flavored liquid (TL) (all containing nicotine), and the corresponding base mixtures (free of nicotine and flavor) were used in three different dilutions. Cytotoxicity was assessed using the water-soluble tetrazolium-8 assay. DNA fragmentation was quantified using alkaline microgel electrophoresis. All liquids caused a significant reduction in cell viability. FLs especially showed a higher toxicity than TL. DNA fragmentation significantly increased by incubation with FL, whereas treatment with TL did not show serious DNA damage. E-liquids are cytotoxic to oropharyngeal tissue, and some liquids can induce relevant DNA damage. Thus, mutagenicity for mucosa of the UADT and e-liquids as risk factors for head and neck cancer cannot entirely be ruled out. Only the implementation of standards and regulations for liquid production and distribution can ensure a valid scientific investigation and assessment of carcinogenic potential of long-term EC use.


Asunto(s)
Carcinoma de Células Escamosas/inducido químicamente , Citotoxinas/toxicidad , Sistemas Electrónicos de Liberación de Nicotina/efectos adversos , Neoplasias de Cabeza y Cuello/inducido químicamente , Mutágenos/toxicidad , Orofaringe/efectos de los fármacos , Adulto , Carcinoma de Células Escamosas/epidemiología , Supervivencia Celular/efectos de los fármacos , Daño del ADN/efectos de los fármacos , Femenino , Alemania/epidemiología , Neoplasias de Cabeza y Cuello/epidemiología , Humanos , Masculino , Membrana Mucosa/efectos de los fármacos , Factores de Riesgo , Carcinoma de Células Escamosas de Cabeza y Cuello , Adulto Joven
19.
Trends Hear ; 202016 10 03.
Artículo en Inglés | MEDLINE | ID: mdl-27698259

RESUMEN

Semi-implantable transcutaneous bone conduction devices are treatment options for conductive and mixed hearing loss (CHL/MHL). For counseling of patients, realistic simulation of the functional result is desirable. This study compared speech recognition in noise with a semi-implantable transcutaneous bone conduction device to external stimulation with a bone conduction device fixed by a headband. Eight German-language adult patients were enrolled after a semi-implantable transcutaneous bone conduction device (Bonebridge, Med-El) was implanted and fitted. Patients received a bone conduction device for external stimulation (Baha BP110, Cochlear) fixed by a headband for comparison. The main outcome measure was speech recognition in noise (Oldenburg Sentence Test). Pure-tone audiometry was performed and subjective benefit was assessed using the Glasgow Benefit Inventory and Abbreviated Profile of Hearing Aid Benefit questionnaires. Unaided, patients showed a mean signal-to-noise ratio threshold of 4.6 ± 4.2 dB S/N for speech recognition. The aided results were -3.3 ± 7.2 dB S/N by external bone conduction stimulation and -1.2 ± 4.0 dB S/N by the semi-implantable bone conduction device. The difference between the two devices was not statistically significant, while the difference was significant between unaided and aided situation for both devices. Both questionnaires for subjective benefit favored the semi-implantable device over external stimulation. We conclude that it is possible to simulate the result of speech recognition in noise with a semi-implantable transcutaneous bone conduction device by external stimulation. This should be part of preoperative counseling of patients with CHL/MHL before implantation of a bone conduction device.


Asunto(s)
Conducción Ósea , Audífonos , Ruido , Percepción del Habla , Adulto , Humanos , Estudios Prospectivos , Habla , Resultado del Tratamiento
20.
PLoS One ; 10(11): e0141827, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26588072

RESUMEN

Head and neck squamous cell cancer (HNSCC) is the 7th most common cancer worldwide. Despite the development of new therapeutic agents such as monoclonal antibodies, prognosis did not change for the last decades. Cold atmospheric plasma (CAP) presents the most promising new technology in cancer treatment. In this study the efficacy of a surface micro discharging (SMD) plasma device against two head and neck cancer cell lines was proved. Effects on the cell viability, DNA fragmentation and apoptosis induction were evaluated with the MTT assay, alkaline microgel electrophoresis (comet assay) and Annexin-V/PI staining. MTT assay revealed that the CAP treatment markedly decreases the cell viability for all tested treatment times (30, 60, 90, 120 and 180 s). IC 50 was reached within maximal 120 seconds of CAP treatment. Comet assay analysis showed a dose dependent high DNA fragmentation being one of the key players in anti-cancer activity of CAP. Annexin-V/PI staining revealed induction of apoptosis in CAP treated HNSCC cell lines but no significant dose dependency was seen. Thus, we confirmed that SMD Plasma technology is definitely a promising new approach on cancer treatment.


Asunto(s)
Carcinoma de Células Escamosas/terapia , Neoplasias de Cabeza y Cuello/terapia , Gases em Plasma/uso terapéutico , Apoptosis/efectos de la radiación , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral , Supervivencia Celular/efectos de la radiación , Fragmentación del ADN/efectos de la radiación , Neoplasias de Cabeza y Cuello/patología , Humanos
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