Claudia Lill

Survival of patients with HPV-positive oropharyngeal cancer after radiochemotherapy is significantly enhanced

ZusammenfassungHINTERGRUND: Der Zweck dieser retrospektiven Studie war, die Inzidenz und klinische Signifikanz von Infektionen mit HPV (Humanes Papillomavirus) in Patienten mit Kopf-Hals-Tumoren, die eine Strahlentherapie erhalten hatten, zu evaluieren. PATIENTEN AND METHODEN: Bei 88 Patienten mit Karzinomen des Kopf-Hals-Bereiches wurde eine Untersuchung zur Identifizierung von high-risk HPV mittels Immunhistochemie, PCR (Polymerase Chain Reaction) und in-situ Hybridisierung durchgeführt. 26 Patienten hatten ein Karzinom der Mundhöhle, 45 des Oropharynx, sieben ein Larynx- und 10 ein Hypopharnyxkarzinom. 29 der 45 Patienten mit einem Plattenepithelkarzinom des Oropharynx erhielten entweder eine alleinige Strahlentherapie oder eine Kombination mit Cisplatin oder Cetuximab. ERGEBNISSE: Von den 29 untersuchten Patienten, die zur Therapie ihres Oropharynxkarzinoms eine konservative Therapie erhielten, hatten 11 Patienten einen HPV positiven und 18 einen HPV negativen Tumor. Den Patienten wurde eine Strahlentherapie ± Cisplatin oder Cetuximab verabreicht, wobei die Patienten mit einem HPV positiven Tumor ein signifikant besseres Ansprechen auf die Therapie zeigten (p = 0.015). Auch das krankheits-spezifische Überleben war deutlich besser in HPV positiven Patienten (p = 0.001). SCHLUSSFOLGERUNG: Patienten mit einem Oropharynxkarzinom und einem positiven HPV Status sprechen deutlich besser auf eine Radiochemotherapie an als Patienten mit einem HPV negativen Tumor. Das HPV Screening ist eine sehr einfache Prozedur und kann einfach routinemässig in die Standard Operational Procedures inkludiert werden.SummaryBACKGROUND: The purpose of this study was to evaluate the incidence and clinical significance of HPV (Human papilloma virus) infection in patients with head and neck cancer who had received radiotherapy in Eastern Austria. PATIENTS AND METHODS: 88 patients with head and neck cancer including 26 patients with oral cavity cancer, 45 patients with oropharyngeal cancer, seven patients with laryngeal carcinoma and ten patients with carcinoma of the hypopharynx were screened for high risk HPV by immunohistochemistry, PCR (Polymerase Chain Reaction) and in-situ hybridization. 29 out of 45 patients with a squamous cell carcinoma of the oropharynx received radiotherapy alone, radiotherapy in combination with cisplatin or cetuximab. RESULTS: Of the investigated 29 patients with oropharyngeal cancer receiving conservative treatment, 11 had a HPV-positive and 18 a HPV-negative tumor. Patients received radiation ± cisplatin or cetuximab, where the HPV-positive patients had a significant better response to treatment and overall survival (p = 0.015) as well as disease-free survival (p = 0.001) after therapy. CONCLUSION: Patients with oropharyngeal carcinoma and a positive HPV status respond considerably better to radiochemotherapy than patients with HPV-negative tumors. HPV screening is a simple procedure and can easily be implemented in routine pathology investigations and should be included in standard operational procedures for the diagnosis and therapy of head and neck cancer patients.

SIGNIFICANT CORRELATION OF PEPTIDYL-PROLYL ISOMERASE OVEREXPRESSION IN MERKEL CELL CARCINOMA WITH OVERALL SURVIVAL OF PATIENTS

An overexpression of PIN1, the peptidyl‐prolyl cis‐trans isomerase, might cause cell cycle arrest and growth inhibition by binding to the p53 protein, a process leading to p53 stabilization. The rationale of this retrospective analysis was to evaluate the expression pattern of PIN1 in Merkel cell carcinomas (MCCs) and its suitability as a prognostic factor.

The effect of cilengitide in combination with irradiation and chemotherapy in head and neck squamous cell carcinoma cell lines.

BackgroundIntegrins are highly attractive targets in oncology due to their involvement in angiogenesis in a wide spectrum of cancer entities. Among several integrin inhibitors under clinical evaluation, cilengitide is the most promising compound. However, little is known about the cellular processes induced during cilengitide therapy in combination with irradiation and cisplatin in head and neck squamous cell carcinoma (HNSCC).Materials and methodsThe cytostatic effect of cilengitide was assessed by proliferation assay in the three HNSCC cell lines SCC25, FaDu and CAL27. Combination experiments with cisplatin and irradiation were performed. Possible synergistic effects were calculated in combination index (CI) analyses. Colony forming inhibition was investigated in clonogenic assays. Real-time PCR arrays were used to evaluate target protein gene expression patterns. Flow cytometry was used to detect apoptosis.ResultsUsed alone, cilengitide has only minor cytotoxic effects in HNSCC cell lines. However, combination with cisplatin resulted in synergistic growth inhibition in all three cell lines. Irradiation showed synergism in short-term experiments and in colony forming assays, an additive effect was detected. Real-time PCR assay detected downregulation of the antiapoptotic protein Bcl-2 after exposure of cells to cilengitide.ConclusionCilengitide in combination with cisplatin and irradiation may be a feasible option for the treatment of patients with head and neck cancer. However, further investigations are required to understand the exact mechanism that leads to synergistic cytotoxicity.ZusammenfassungHintergrundDurch ihre Rolle bei der Angiogenese sind Integrine ein attraktives Ziel in der onkologischen Forschung. Der derzeit vielversprechendste Inhibitor dieser Moleküle ist Cilengitide, welches bereits in klinischen Studien getestet wird. Dennoch ist erst wenig über die zellulären Vorgänge bekannt, welche durch Cilengitide in Kopf-Hals-Karzinomen (HNSCC) insbesondere in Kombination mit Strahlentherapie und Cisplatin ausgelöst werden.Material und MethodenDer zytostatische Effekt von Cilengitide wurde in drei Kopf-Hals-Zelllinien SCC25, CAL27 und FaDu mittels Proliferationsassay überprüft. Mit Cisplatin und Bestrahlung wurden Kombinationsexperimente durchgeführt. Mögliche Synergien wurden mittels Kombinationsindex-(CI-)Analyse berechnet. Der Einfluss auf die Koloniebildung wurde in Koloniebildungsexperimenten gezeigt. In Real-time-PCR-Arrays wurden die Expressionsmuster von bekannten Zielproteinen untersucht. Mittels FACS („flow cytometry“) wurde nach Apoptose gesucht.ResultateCilengitide selbst hatte nur eine geringe direkte Wirkung auf das Wachstum unserer Zelllinien. Die Kombination mit Cisplatin jedoch zeigte eine synergistische Wachstumshemmung. In Kurzzeitexperimenten war Cilengitide in Kombination mit Bestrahlung synergistisch. Auch in den Koloniebildungsassays konnte ein additiver Effekt nachgewiesen werden. Das antiapoptotische Bcl-2-Protein wurde nach Exposition mit Cilengitide vermindert exprimiert.SchlussfolgerungCilengitide in Kombination mit Cisplatin und Bestrahlung könnte eine sinnvolle Behandlungsoption für Patienten mit Kopf-Hals-Karzinomen sein. Dafür sind jedoch noch weitere Experimente notwendig, auch um den exakten Mechanismus der Synergie zu verstehen.

Milk allergy is frequent in patients with chronic sinusitis and nasal polyposis.

Background Chronic sinusitis and nasal polyps with subsequent nasal blocking, anosmia, and relapsing infections are frequent in the rhinological practice. Often, recurrent disease necessitates repetitive conservative therapy and surgical treatment (functional endoscopic sinus surgery). This study was initiated to scrutinize the relationship of wheat and milk allergies to chronic polypoid sinusitis (CPS) and recurrent disease. Methods Blood samples of 50 healthy controls and 50 patients with clinically and radiologically diagnosed CPS and nasal polyposis were screened for common food allergies including wheat and milk allergy. On inclusion into the study, none of the patients reported a symptomatic food allergy. Results Fifteen of 100 tested subjects (15%) revealed a previously undiagnosed allergy to inhalant (dust, rye, and pollens) and other food allergens (corn and egg white). Six of 50 patients (12%) with CPS exhibited a wheat allergy, and a milk allergy could be identified in 7 patients (14%). In the control group, seven healthy subjects (14%) showed a wheat allergy and no case of milk allergy could be identified (p = 0.0125). Conclusion In contrast to previous studies in other countries presenting a food allergy incidence of ∼75% in patients with nasal polyposis, we could not show such a high incidence. In the group with chronic polyposis 14% of the patients were positive for milk allergy compared with none of the tested healthy subjects, resulting in a strong statistical significance. Therefore, we conclude that cows milk but not wheat allergy might be a relevant pathogenetic entity in chronic nasal polyps.

Correlation of β-catenin, but not PIN1 and cyclin D1, overexpression with disease-free and overall survival in patients with cancer of the parotid gland

Malignant tumors of the salivary glands comprise about 3% to 5% of all head and neck carcinomas. The purpose of our study was to find possible predictive and/or prognostic markers for parotid cancer.

Sealing of the round and oval window niches with triamcinolone-soaked fascia as salvage surgical therapy in sudden sensorineural hearing loss

Abstract Conclusions: Triamcinolone-soaked fascia seems to show better hearing improvement when added to tympanotomy for sudden idiopathic sensorineural hearing loss (SSHL), compared to fascia round window occlusion without triamcinolone. Objectives: To analyse if adding triamcinolone to sealing the round and oval window niches with fascia results in improved audiological outcome for acute SNHL. Methods: Fifty-three patients (27m:43 ± 12 years, 26f:45 ± 14 years) with acute SSHL ≥50dB over 3 frequencies, who failed primary therapy, underwent transcanal tympanotomy. Twenty-five patients (Group A;cortisone:14m, 11f:46 ± 9 years) received sealing of the round and oval window with fascia soaked in triamcinolone (1ml; 40mg/ml) and 28 controls (Group B;no-cortisone:13m, 15f, 42 ± 12 years) without triamcinolone. Frequency specific and pure tone average (PTA =500–1000–2000–3000Hz) results were compared between Group A and B pre- and postoperatively. Results: In Group A the PTA improved by ≥10dB in 21/25(83%) cases; in Group B 18/28(63%). Group A showed a statistically significantly better improvement across all frequencies, while linear regression revealed a significant decrease of posttherapeutic PTA to 94.96% of the initial PTA (p = .037). The overall PTA improved by 24dB. Group A improved from 73dB to 41dB(-32dB) PTA, Group B improved from 76dB to 56dB PTA (-20dB) (p < .05). Group A showed a significant additional decrease of 12.8dB (p < .001).

Effects of neratinib and combination with irradiation and chemotherapy in head and neck cancer cells

OBJECTIVE Prognosis of patients with head and neck squamous cell carcinoma (HNSCC) is still poor. Novel therapeutic approaches are of great interest to improve the effects of radiochemotherapy. We evaluated the effects of tyrosine kinase inhibitor neratinib on HNSCC cell lines CAL27, SCC25 and FaDu as a single agent and in combination with irradiation and chemotherapy. METHODS Effects of neratinib were evaluated in HNSCC cell lines CAL27, SCC25 and FaDu. Effect on cell viability of neratinib and combination with cisplatin and irradiation was measured using CCK-8 assays and clonogenic assays. Western blot analysis was performed to distinguish the effect on epithelial growth factor receptor and HER2 expression. Apoptosis was evaluated by flow cytometry analysis. RESULTS Growth inhibition was achieved in all cell lines, whereas combination of cisplatin and neratinib showed greater inhibition than each agent alone. Apoptosis was induced in all cell lines. Combination of neratinib with irradiation or cisplatin showed significantly increased apoptosis. In clonogenic assays, significant growth inhibition was observed in all investigated cell lines. CONCLUSION Neratinib, as a single agent or in combination with chemo-irradiation, may be a promising treatment option for patients with head and neck cancer.

The effect of tonsillotomy on chronic recurrent tonsillitis in children

Abstract Objectives: The objective of this study is to determine whether partial tonsillectomy (tonsillotomy) impacts the occurrence of acute or recurrent tonsillitis in children. Methods: One hundred and eighty patients (1–14 years) were retrospectively surveyed by a questionnaire or by data analysis of a regional database. Subjects who suffered from severe systemic diseases or immunodeficiency syndromes were excluded. Episodes of acute tonsillitis before and after surgery, rate of antibiotic treatment, postoperative hemorrhage, and re-operation were obtained. Results: Fifty-one patients suffered from preoperative tonsillitis. The rate of reinfection was 9.8%. The frequency of tonsillitis was significantly reduced in children after tonsillotomy (p < .001). Further, tonsillotomy led to a significant reduction of antibiotic treatment (p < .001). The rate of definitive tonsillectomy was 1.1% and thus effectiveness was very high. About 1.7% of all children suffered from postoperative bleeding, of which one (0.6%) required surgical revision. None of the bleedings was life threatening. Conclusions: Tonsillotomy is beneficial for patients with recurrent tonsillitis and carries less risk of postoperative complications than tonsillectomy.