Markus Hambek

Cochlear Implantation Via the Round Window Membrane Minimizes Trauma to Cochlear Structures: A Histologically Controlled Insertion Study

Objective To evaluate cochlear implant trauma to intracochlear structures when inserting the electrode via the round window membrane. Material and methods Eight fresh human temporal bones were evaluated histologically after insertion using two types of cochlear implant array. Bones underwent a special fixation and embedding procedure that allowed sectioning of undecalcified bone with the electrode in situ. Insertions depths were evaluated radiologically and histologically. Results All arrays were found in the scala tympani of the cochlea. Basal trauma could be avoided in all but one specimen. The mean depth of insertion was 382.5°. Apically, only one implanted bone showed cochlear trauma exceeding lifting of the basilar membrane. Conclusion Insertions through the round window membrane were shown to be atraumatic, even in basal cochlear regions. This route of insertion might be very effective for combined electric and acoustic stimulation of the auditory system.

Preservation of Basal Inner Ear Structures in Cochlear Implantation

The aim of this report was to examine basal trauma in implanted human temporal bones and discuss modified approaches to the basal cochlear turn to avoid destruction of basal cochlear structures. Thirty-three human temporal bones were implanted with four different cochlear implant electrode arrays manufactured by MED-EL using either a caudal approach cochleostomy or round window membrane insertions. All specimens were processed with a special histological technique that allows sectioning of undecalcified bone with the electrode in situ. All bones were evaluated histologically in terms of basal cochlear trauma. Two pathomechanisms of basal trauma could be distinguished and were evaluated separately, buckling of the basal end of the array and trauma by drilling. Using the caudal approach cochleostomy, the total percentage of destructive basal trauma was 48% compared to less than 15% when performing round window membrane insertions. Although it is still unclear whether basal cochlear trauma influences apical cochlear function or not, adapted surgical procedures and no forceful insertion maneuvers should be used when performing cochlear implantations with hearing preservation.

Combined Cetuximab and Reirradiation for Locoregional Recurrent and Inoperable Squamous Cell Carcinoma of the Head and Neck

Purpose:To investigate the feasibility, toxicity, and efficacy of external-beam reirradiation (Re-RT) combined with cetuximab for patients with inoperable and recurrent squamous cell carcinoma of the head and neck (SCCHN).Patients and Methods:Seven patients with inoperable recurrence of SCCHN after adjuvant or definitive radiotherapy (RT) and simultaneous or sequential cisplatin-based chemotherapy for primary SCCHN were treated between August and December 2008 with Re-RT (1.8 Gy/fraction to 50.4 Gy) and cetuximab (400 mg/m2 initial dose in the 1st week, and then 250 mg/m2 once weekly). Recurrence had to be located at least ≥ 50% in the preirradiated field. Long term toxicity from previous treatment was recorded before Re-RT as a baseline value. Acute and late toxicity derived from the experimental regimen were recorded every week during RT, and then every 3 months. Efficacy was assessed with repeated imaging using response evaluation criteria in solid tumors (RECIST) and clinical examinations 8–12 weeks after end of the treatment and every 3 months thereafter (Tables 1 and 2).Results:Only mild localized mucositis occurred in all patients. Two patients developed a grade 3 acneiform rash related to cetuximab. After treatment one patient developed a grade 2 trismus, another showed grade 3 abacterial salivary gland inflammation with severe pain requiring opioid medication. Two patients achieved a complete response after 7 months, one remained stable, three progressed, and one died from pneumonia without having restaging magnetic resonance imaging.Conclusion:A second course of RT combined with cetuximab in patients with inoperable, recurrent HNSCC proved to be feasible with mild or moderate toxicity and encouraging response to treatment.Ziel:Erfassung der Durchführbarkeit, Nebenwirkungen und Effizienz einer perkutanen Rebestrahlung (Re-RT) zusammen mit Cetuximab bei Patienten mit inoperablen und rezidivierten Plattenepithelkarzinomen der Kopf-Hals-Region ((CCHN).Patienten and Methodik:Sieben Patienten mit inoperablen, rezidivierten SCCHN nach adjuvanter oder definitiver Radiotherapie (RT) und simultaner oder sequentieller cisplatinbasierter Chemotherapie wurden zwischen August und Dezember 2008 mit einer Re-RT (1,8 Gy bis 50,4 Gy) und Cetuximab (400 mg/m2 Anfangsdosis in der 1. Woche und danach 250 mg/m2 einmal wöchentlich) behandelt. Die Rezidivlokalisation musste zu mehr als 50% in der vorbestrahlten Region liegen. Vor Beginn der Re-RT wurden die Nebenwirkungen durch die vorangegangenen Therapien als Ausgangswerte erfasst. Die Akutnebenwirkungen und Spätfolgen durch die experimentelle Behandlung wurden wöchentlich während Re-RT, und dann alle 3 Monate erhoben. Das Therapieansprechen wurde mit wiederholter Bildgebung, anhand der RECIST-Kriterien („response evaluation criteria in solid tumors“) und klinischen Untersuchungen 8–12 Wochen nach Beendigung der Re-RT und danach alle 3 Monate erhoben.Ergebnisse:Bei allen Patienten trat eine milde lokalisierte Mukositis auf. Zwei Patienten zeigten eine Grad-3-Akne auf Cetuximabgabe. Nach der Re-RT entwickelte ein Patient einen Trismus (Grad 2), ein anderer eine abakterielle Grad-3-Sialadenitis mit starken Schmerzen, die einer Opioidmedikation bedurften. Zwei Patienten erreichten 7 Monate nach Re-RT eine komplette Remission, einmal zeigt sich der Rezidivtumor stabil, drei waren progredient, und ein Patient verstarb an einer Pneumonie ohne erneute Bildgebung.Schlussfolgerung:Für Patienten mit inoperablen, rezidivierten HNSCC erweist sich eine erneute RT zusammen mit Cetuximab mit nur geringen oder moderaten Nebenwirkungen und ermutigendem Therapieanspechen als durchführbar.

Patient-based cross-platform comparison of oligonucleotide microarray expression profiles

The comparison of gene expression measurements obtained with different technical approaches is of substantial interest in order to clarify whether interplatform differences may conceal biologically significant information. To address this concern, we analyzed gene expression in a set of head and neck squamous cell carcinoma patients, using both spotted oligonucleotide microarrays made from a large collection of 70-mer probes and commercial arrays produced by in situ synthesis of sets of multiple 25-mer oligonucleotides per gene. Expression measurements were compared for 4425 genes represented on both platforms, which revealed strong correlations between the corresponding data sets. Of note, a global tendency towards smaller absolute ratios was observed when using the 70-mer probes. Real-time quantitative reverse transcription PCR measurements were conducted to verify expression ratios for a subset of genes and achieved good agreement regarding both array platforms. In conclusion, similar profiles of relative gene expression were obtained using arrays of either single 70-mer or multiple short 25-mer oligonucleotide probes per gene. Although qualitative assessments of the expression of individual genes have to be made with caution, our results indicate that the comparison of gene expression profiles generated on these platforms will help to discover disease-related gene signatures in general.

Demands on caring relatives of head and neck cancer patients

Background: Relatives of cancer patients experience high levels of stress that influence the quality of life of these individuals. To investigate whether there is a necessity for simultaneous supportive care of patient relatives, we performed for the first time a study asking the closest relatives of head and neck cancer patients about their needs during and after the treatment to consider how to optimize the situation for such patient groups.

Usefulness of MRI volumetric evaluation in patients with squamous cell cancer of the head and neck treated with neoadjuvant chemotherapy

The purpose was to evaluate the efficacy of tumor volumetry on MRI as predictive of response to treatment with induction chemotherapy, comparing the results with endoscopy.

Inverse correlation between serum PGE2 and T classification in head and neck cancer

Prostaglandin E2 (PGE2) serum levels have been shown previously to be increased in tumor bearing mice as well as in patients with solid tumors; however, the impact on the course or stage of disease has not been shown. We hypothesized that PGE2 is strictly required for aggressive and especially early‐stage tumors of the head and neck to provoke invasion and angiogenesis.

Reirradiation With Cetuximab in Locoregional Recurrent and Inoperable Squamous Cell Carcinoma of the Head and Neck: Feasibility and First Efficacy Results

PURPOSE To report our experience with a prospective protocol of external beam reirradiation (Re-RT) combined with cetuximab for patients with inoperable, recurrent squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS Between August 2008 and June 2010, 18 patients with inoperable recurrence of SCCHN after adjuvant or definitive radiotherapy (RT) and simultaneous or sequential cisplatin-based chemotherapy for primary SCCHN were enrolled. Acute and late toxicity from the experimental regimen were recorded every week during RT and every 3 months thereafter. Efficacy was assessed with repeated imaging using response evaluation criteria in solid tumors and clinical examinations 8-12 weeks after completion of the treatment and every 3 months thereafter. RESULTS Median follow-up time for all patients was 9.4 (range: 3.85-31.7) months and for patients alive 30.4 (range: 15.7-31.7) months. Acute toxicity was generally mild or moderate. Five patients developed a grade 3 acneiform rash related to cetuximab. Late toxicity occurred as grade 3 trismus in five and as grade 3 abacterial salivary gland inflammation in one patient, respectively. Overall response rate was 47%. Median overall and progression-free survival for all patients was 8.38 months and 7.33 months, respectively. The overall survival rate was 44% at 1 year, with a 1 year local control rate of 33%. CONCLUSION Notwithstanding the limitations of our preliminary data Re-RT combined with cetuximab for recurrent and inoperable SCCHN is feasible and the integration of newer targeted agents seems to be less toxic compared to conventional chemotherapy with encouraging response rates at least for a subset of patients.

AdOnco : A database for clinical and scientific documentation of head and neck oncology

Objectives: The aim of this project was to design, develop, and implement a head and neck cancer computer database for clinical and scientific use. Methods: A relational database based on Filemaker Pro 6.0 was developed and integrated into our local network. A precise and easy-to-handle interface should allow for a quick overview of the patients oncological history and for optimized data acquisition. An automatic report function was integrated to enhance the quality of daily patient care. For evaluation purposes, statistical analysis functions were implemented. Results: Over a 14-month period, 410 patient records were available through the local network. The automated report function and the well-organized screen desktop resulted in time-efficient and accurate patient care. Additionally, the quality of information presented to referring physicians increased notably. The statistical analysis data provided by the database were reliable and easy to export. Conclusions: We developed an oncology database for both clinical and scientific purposes and integrated it successfully into our patient documentation system. The combination of clinical and scientific features proved to be very effective in daily routine and research.

The role of recombinant epidermal growth factor and serotonin in the stimulation of tumor growth in a SCCHN xenograft model.

One challenge of squamous cell carcinoma of the head and neck (SCCHN) chemotherapy is a small percentage of tumor cells that arrest in the G0 phase of the cell cycle and are thus not affected by chemotherapy. This could be one reason for tumor recurrence at a later date. The recruitment of these G0-arresting cells into the active cell cycle and thus, proliferation, may increase the efficacy of chemotherapeutic agents. The aim of this study was to investigate whether stimulation with recombinant epidermal growth factor (EGF) or serotonin leads to an increased tumor cell proliferation in xenografts. Detroit 562 cells were injected into NMRI-Foxn1nu mice. Treatment was performed with 15 μg murine or human EGF, or 200 μg serotonin. The control mice were treated with Lactated Ringer’s solution (5 mice/group). Tumor size was measured on days 4, 8 and 12 after tumor cell injection. The EGF stimulated mice showed a significantly higher tumor growth compared to the serotonin-stimulated mice and the untreated controls. In the present study, we show that it is possible to stimulate tumor cells in xenografts by EGF and thus, enhance cell proliferation, resulting in a higher tumor growth compared to the untreated control group. In our future investigations, we plan to include a higher number of mice, an adjustment of the EGF dosage and cell subanalysis, considering the heterogeneity of SCCHN tumors.