[Structured oral examination ("guided questions") as a method for objectifying the ENT specialist examination in Germany]. / Strukturierte mündliche Prüfung ("guided questions") als Methode zur Objektivierung der HNO-Facharztprüfung in Deutschland.

On behalf of the federal Ministries of Health, the various German medical associations organize and conduct the board certification examinations for becoming an ENT specialist at the end of residency. The oral examination comprises a collegial discussion that should last at least 30 min and which rarely exceeds 45 to 60 min in practice. The current article describes the quality criteria upon which examinations in general should be based, and lists the most common mistakes during conduction of oral examinations. Using "oral guided questions" (OGQ or GQ) can guarantee a high degree of standardization, objectivity, transparency, and justiciability. The principles of a GQ-guided examination are described and specified by a typical example. Experiences with this form of examination from the federal states of Brandenburg and Thuringia are presented.

[MEDCARE for People in Eritrea : A report on 9 years' help through self-help]. / MEDCARE for People in Eritrea : Ein Bericht über 9 Jahre Hilfe zur Selbsthilfe.

The current article is an experience report on the establishment of an ENT clinic in Asmara/Eritrea and the organization of regular work stays for the further education of local colleagues. Objectives of the project are content and structural support for self-help and thus achievement of sustainable development aid, which benefits both the medical development of the country and the care of the local patients.

[Tonsil surgery in Brandenburg-trends between 2013 and 2017]. / Operationen an den Gaumenmandeln im Land Brandenburg ­ Entwicklungen von 2013 bis 2017.

BACKGROUND: The frequency of tonsil surgery in Brandenburg (BB) during the period from 2013 to 2017 is analyzed. Causes and possible consequences of the trends are discussed. MATERIALS AND METHODS: An OPS code-based survey is carried out in the 10 ENT hospitals in BB and using the data from the federal states (Federal Statistical Office). In addition, the respective heads of ENT departments are interviewed concerning the indication for tonsillectomy (TE). The average number of operations in 2013/2014 is compared to that in 2017 (BB) and 2016 (federal states). RESULTS: In 9/10 participating hospitals in BB, 10,302 operations were performed, thereof 58.4% as TE, 19.0% as tonsillotomy (TT), 13.7% as abscess tonsillectomy (abscess TE), and 8.9% other. In BB in 2017 in comparison to 2013/2014, because of the decrease in TE by 45.6%, a total of 21.1% less operations were performed, while TT and abscess TE increased by 32% and 18%, respectively. The average age at surgery was 28.1, 38.1, and 5.9 years for TE, abscess TE, and TT, respectively. The entire trend for Germany until 2016 on the basis of 395,674 cases reflects a decrease in TE (30.7%) and abscess TE (14%), while TT was performed 27.5% more often, resulting in a total decrease of 21.3%. The interviewed persons follow the "justifiable operation indications" of the German guideline from 2015 and adapted their previous practice. CONCLUSION: Our survey and results indicate that the massive decrease of TE in BB is associated with the "justifiable operation indications" of the 2015 German guidelines on inflammatory diseases of the tonsils. TE is mainly performed in adults. Therefore, research concerning conservative versus surgical treatment for recurrent tonsillitis is urgently needed for this age profile.

Induction chemotherapy (IC) followed by radiotherapy (RT) versus cetuximab plus IC and RT in advanced laryngeal/hypopharyngeal cancer resectable only by total laryngectomy-final results of the larynx organ preservation trial DeLOS-II.

Background: The German multicenter randomized phase II larynx organ preservation (LOP) trial DeLOS-II was carried out to prove the hypothesis that cetuximab (E) added to induction chemotherapy (IC) and radiotherapy improves laryngectomy-free survival (LFS; survival with preserved larynx) in locally advanced laryngeal/hypopharyngeal cancer (LHSCC). Patients and methods: Treatment-naïve patients with stage III/IV LHSCC amenable to total laryngectomy (TL) were randomized to three cycles IC with TPF [docetaxel (T) and cisplatin (P) 75 mg/m2/day 1, 5-FU (F) 750 mg/m2/day days 1-5] followed by radiotherapy (69.6 Gy) without (A) or with (B) standard dose cetuximab for 16 weeks throughout IC and radiotherapy (TPFE). Response to first IC-cycle (IC-1) with ≥30% endoscopically estimated tumor surface shrinkage (ETSS) was used to define early responders; early salvage TL was recommended to non-responders. The primary objective was 24 months LFS above 35% in arm B. Results: Of 180 patients randomized (July 2007 to September 2012), 173 fulfilled eligibility criteria (A/B: larynx 44/42, hypopharynx 41/46). Because of 4 therapy-related deaths among the first 64 randomized patients, 5-FU was omitted from IC in the subsequent 112 patients reducing further fatal toxicities. Thus, IC was TPF in 61 patients and TP in 112 patients, respectively. The primary objective (24 months LFS above 35%) was equally met by arms A (40/85, 47.1%) as well as B (41/88, 46.6%). One hundred and twenty-three early responders completed IC+RT; their overall response rates (TPF/TP) were 94.7%/87.2% in A versus 80%/86.0% in B. The 24 months overall survival (OS) rates were 68.2% and 69.3%. Conclusions: Despite being accompanied by an elevated frequency in adverse events, the IC with TPF/TP plus cetuximab was feasible but showed no superiority to IC with TPF/TP regarding LFS and OS at 24 months. Both early response and 24 months LFS compare very well to previous LOP trials and recommend effective treatment selection and stratification by ETSS. Clinical trial information: NCT00508664.

A two-arm multicenter phase II trial of one cycle chemoselection split-dose docetaxel, cisplatin and 5-fluorouracil (TPF) induction chemotherapy before two cycles of split TPF followed by curative surgery combined with postoperative radiotherapy in patients with locally advanced oral and oropharyngeal squamous cell cancer (TISOC-1).

BACKGROUND: Induction chemotherapy (ICT) with docetaxel, cisplatin and fluorouracil (TPF) followed by radiotherapy is an effective treatment option for locally advanced head and neck cancer. This phase II study investigated the effectivity of a split-dose TPF ICT before surgery for locally advanced resectable (stage III/IVA) oral and oropharyngeal cancer. PATIENTS AND METHODS: Patients received TPF split on two dosages on days 1 and 8 per cycle (30 mg/m2 docetaxel, 40 mg/m2 cisplatin, 2000 mg/m2 fluorouracil per week). Responders (reduction tumor volume ≥30% after first cycle) received three 3-week cycles and non-responders only one cycle before surgery and postoperative radio(chemo)therapy (RCT). The primary endpoint was progression-free survival rate after 24 months. Secondary endpoints were amongst others overall survival, histopathological response to ICT, toxicity, quality of life and swallowing function. RESULTS: Fifty-four patients (91% stage IVA, 87% male, 72% oropharyngeal cancer, 70% responders) were eligible for a per-protocol analysis. The progression-free survival rate after 24 months was 88.5% for responders and 60.6% for non-responders (P = 0.005). The overall survival rate after 24 months was 97.3% for responders and 73.7% for non-responders (P = 0.032). The rate of histopathological complete remission of the primary tumor was higher in responders (P = 0.015). High-risk classification for postoperative RCT was lower in responders (P < 0.0001). The most common grade 3+ adverse event was neutropenia in 26% of patients during ICT and mucositis in 13% during postoperative RCT. During treatment and follow-up quality of life and swallowing function was not different between responders and non-responders. CONCLUSION: Patients with oral and oropharyngeal cancer responding to split-dose TPF before surgery and postoperative RCT show good oncological results. The tri-modal treatment regime was well tolerated. ICT using tumor response as criterion for duration of ICT before surgery of oral and oropharyngeal cancer merits additional investigation in a phase III study. CLINICAL TRIAL NUMBER: NCT01108042.

[Obstructive sleep apnea syndrome in the setting of Gorlin-Goltz syndrome]. / Obstruktives Schlafapnoe-Syndrom bei Gorlin-Goltz-Syndrom.

Goltz-Gorlin syndrome is a rare autosomal dominant hereditary disease associated with a high rate of spontaneous mutation. Diagnosis is based on clinically defined major and minor criteria. The disease is caused by a gene mutation locating to chromosome 9q22-31. We report on a young Goltz-Gorlin syndrome patient with obstructive sleep apnea syndrome. Due to intolerance to continuous positive airway pressure (CPAP) therapy and in order to avoid a tracheotomy, we opted for an alternative therapy comprising interdisciplinary multi-level surgery.

[Atlantoaxial malformation as a rare cause of dysphagia and snoring]. / Eine atlantoaxiale Fehlbildung als seltene Ursache für Dysphagie und Rhonchopathie.

Abnormalities of the atlantoaxial spine are very rare variants. Bony outgrowths, osteophytes, clefts and aplasia may be misinterpreted as degenerative diseases. One patient presented with intermittent dysphagia and snoring and CT and MRI scans of the cervical spine showed an accessory bone located anterior to the atlas and axis. Atlantoaxial anomalies are often incidental findings without clinical symptoms. Such changes are rarely the cause of intermittent dysphagia and snoring.

["Hybrid tracheostomy": a low risk procedure for tracheostomy in COVID-19 patients]. / "Hybridtracheostomie" ­ ein risikoarmes Verfahren der Tracheostomie bei COVID-19-Patienten.

BACKGROUND: Tracheostomy in ventilated patients suffering from Coronavirus disease 2019 (COVID-19) carries an increased risk of exposure to virus-containing aerosol for the staff. OBJECTIVE: Evaluation of a risk-reduced procedure for tracheostomy. METHOD: Presentation of "hybrid tracheostomy": a method combining the advantages of conventional surgical and percutaneous dilative tracheostomy. RESULTS: Tracheostomy of six patients using the hybrid method without any complications. CONCLUSION: "Hybrid tracheostomy" offers a minimally invasive and safe procedure with low risk of exposure to virus-containing aerosol.

Regurgitant flow in cardiac valve prostheses: diagnostic value of gradient echo nuclear magnetic resonance imaging in reference to transesophageal two-dimensional color Doppler echocardiography.

Gradient echo nuclear magnetic resonance (NMR) imaging and transesophageal two-dimensional color Doppler echocardiography are flow-sensitive techniques that have been used in the diagnosis and grading of valvular regurgitation. To define the diagnostic value of gradient echo NMR imaging in the detection of regurgitant flow in cardiac valve prostheses and the differentiation of physiologic leakage flow from pathologic transvalvular or paravalvular leakage flow, 47 patients with 55 valve prostheses were examined. Color Doppler transesophageal echocardiography was used for comparison. Surgical confirmation of findings was obtained in 11 patients with 13 valve prostheses. Gradient echo NMR imaging showed regurgitant flow in 37 of 43 valves with a jet seen on transesophageal echocardiography and it detected physiologic leakage flow in 4 additional valves. There was 96% agreement between the two methods in distinguishing between physiologic and pathologic leakage flow. The methods differed on jet origin of pathologic leakage flow in six prostheses. The degree of regurgitation was graded by both NMR imaging and transesophageal echocardiography, according to the area of the regurgitant jet visualized; gradings were identical for 75% of valve prostheses. Quantification of jet length and area showed a good correlation between the two methods (r = 0.85 and r = 0.91, respectively). Gradient echo NMR imaging is a useful noninvasive technique for the detection, localization and estimation of regurgitant flow in cardiac valve prostheses. However, because transesophageal echocardiography is less time-consuming and less expensive, gradient echo NMR imaging is unlikely to displace transesophageal echocardiography and should be used only in the occasional patient who cannot be adequately imaged by echocardiography.

Coamplification of the hst and bcl-1 oncogenes in advanced squamous cell carcinomas of the head and neck.

Squamous cell carcinomas of the head and neck from 40 untreated patients were analysed for rearranged or amplified proto-oncogenes by Southern blot hybridisation. The bcl-1 and the hst genes were coamplified 8-32-fold in 5 patients (12.5%). Only males with stage III and IV disease showed coamplification of these oncogenes. Northern blot analysis of the positive samples did not show expression of bcl-1 or hst genes. In contrast, a third oncogene located on chromosome 11 (Ha-ras-1) was not amplified in these tumours. Disease development was observed in all cases over a minimum period of 3 years. Survival of the patients with coamplification of hst/bcl-1 seemed to be shorter than of those with stage III and IV disease without amplification. This difference was not significant probably due to the small number of investigated patients.

Feasibility of high-dose dipyridamole-magnetic resonance imaging for detection of coronary artery disease and comparison with coronary angiography.

To assess the feasibility, safety and usefulness of gradient-echo magnetic resonance imaging (MRI) combined with pharmacologic stress testing for the detection of coronary artery disease, 23 patients without previous myocardial infarction but with significant stenosis (greater than 70% diameter stenosis) of greater than or equal to 1 major coronary artery were selected for dipyridamole-MRI stress testing. Each patient underwent MRI at rest, and high-dose dipyridamole-MRI (0.75 mg/kg over 10 minutes) of corresponding basal and midventricular short-axis tomograms. Additionally, these patients performed symptom-limited exercise stress tests. All short-axis tomograms were evaluated on a standardized segmental basis by grading each segment as normal, hypokinetic, akinetic or dyskinetic. Dipyridamole-MRI was considered pathologic if segmental wall motion deteriorated by greater than or equal to 1 grade after dipyridamole. For comparison with coronary angiography, segmental wall motion gradings were related to the respective coronary artery territories in the short-axis plane. Pathologic dipyridamole-MRI was obtained in 18 of 23 (78%) patients. For 1- and 2-vessel diseases, sensitivity was 69 and 90%, respectively. Exercise stress tests were pathologic in 14 of 23 (66%) patients. For 1- and 2-vessel diseases, sensitivity of exercise stress test was 58% (7 of 12 patients) and 77% (7 of 9), respectively. Sensitivity/specificity of dipyridamole-MRI for the localization of the stenosed coronary artery was 78/100% for left anterior descending, 73/100% for left circumflex, and 88/87% for right coronary artery stenoses. It is concluded that dipyridamole-MRI is a feasible nonexercise-dependent test for detection and localization of functionally significant coronary artery disease.

Analysis of protooncogenes in squamous-cell carcinomas of the head and neck (scchn).

We have analysed DNA and RNA from 40 untreated head and neck cancers for amplified and overexpressed proto-oncogenes by Southern and Northern blot hybridisation. Coamplification but no expression of the bcl-1 and the hst genes was found in 12.5% of the patients. Furthermore, amplifications of c-myc were found in 10%, of Ha-ras and c-erbB-2 in 5%. c-erbB-2 amplification was accompanied by gene expression but no overexpression. Correlating our results with clinicopathological data of the patients amplifications were only found in stage III and IV disease (p=0.0164). No correlation was found between amplification and primary tumour site, histopathological differentiation of the tumours, response to induction chemotherapy, or survival. Our results indicate that oncogene amplification in advanced SCCHN reflects more the general genomic instability of advanced tumours than be a reason for tumour growth.

Hypothyroidism after therapy for larynx and pharynx carcinoma.

Early detection of local and regional recurrence is the main goal during follow-up of patients with larynx and pharynx cancer. Hypothyroidism occurring in those patients stays frequently undiagnosed as screening for hypothyroidism is not part of the routine follow-up. This study was performed to assess the prevalence of hypothyroidism in these patients. We included 120 patients (106 male, 14 female) with larynx or pharynx cancer treated more than 2 months earlier (mean = 41 months) in the study. Cancer treatment consisted of either surgery (n = 44), radiotherapy (n = 15), or surgery combined with postoperative radiotherapy (n = 61). In all patients, thyroid function studies (thyrotropin [TSH], free triiodothyronine [FT3], and free thyroxine [FT4]) were performed. Twenty-six of all patients (22%) were hypothyroid; in two patients hypothyroidism was diagnosed postoperatively and these two patients were on replacement therapy with thyroid hormones. The highest rate of hypothyroidism (34%) was present in patients treated with surgery combined with radiotherapy, whereas among patients treated with surgery only 7% were hypothyroid (p < 0.001). There was no difference in the duration of follow-up between therapy and inclusion in the study between those two groups. Two of 15 patients treated only with radiotherapy were diagnosed hypothyroid, but in this group the latency was shorter (p < 0.05). The results indicate that thyroid function studies should be routinely performed in the follow-up of head and neck cancer patients, especially if radiotherapy was part of the treatment.

Prognostic significance of Ki-67 (MIB1), PCNA and p53 in cancer of the oropharynx and oral cavity.

Up to now results concerning the prognostic value of tumor proliferation markers in squamous cell head and neck carcinoma have been equivocal. Beside biological reasons, different treatment modalities are hypothetically responsible for contradictory findings. The aim of this study was to investigate the relationship between proliferative capacity, represented by the immunohistochemical labeling index of proliferation markers Ki-67, PCNA and p53 status, and treatment failure in a matched-pair study design of recurrent and non-recurrent carcinoma initially treated with primary surgery combined with curative post-operative radiation. From a group of 239 patients with T1-T3 carcinoma of the oropharynx or oral cavity, 28 patients with recurrent disease were selected and matched with 28 patients with non-recurrent disease regarding stage and location of tumor as well as age and therapy. All patients received primary surgery combined with post-operative radiation. Immunohistochemistry determined the p53 status and the PCNA and MIB1 (Ki-67) labeling index. The Ki-67 labeling index was significantly (p=0.032) higher in tumors from patients suffering from treatment failure (mean=59. 1%) than in non-failures (mean=50.5%). Carcinoma with a Ki-67 (MIB1) labeling index above the median (53.7%) of the general study population showed a mean time to relapse of 45 months (n=25), whereas mean time-to-relapse was 61.7 months for those cases (n=31) below the median of the general study population (p=0.029). The PCNA labeling index did not correlate significantly with tumor recurrence (mean=50.2% for treatment failures, 45% for non-failures, p=0.31), nor with time-to-relapse (p=0.26). Forty-six percent of tumors showed p53 over-expression. However, there was no significant correlation between p53 over-expression and tumor recurrence or time-to-relapse. We present the largest series of oropharyngeal and oral cavity carcinoma investigated by immunohistochemistry in a controlled study. We conclude that a high Ki-67 labeling index is an indicator for treatment failure in these patients. Like other investigations for different head and neck subsites, we found no relationship between p53 or PCNA status and tumor prognosis. Our data, obtained from a group of patients treated with a combination of surgery and post-operative irradiation, show that for squamous cell carcinoma of the oropharynx and oral cavity the detection of Ki-67 is an unfavorable prognostic factor.

Cyclin-dependent kinase-inhibitor 1 (CDKN1A) in the squamous epithelium of the oropharynx: possible implications of molecular biology and compartmentation.

The cdknlA gene encodes CDKN1A, a protein that regulates cell cycle progression, terminal differentiation, and apoptosis. Polymorphisms or loss of heterozygosity of this usually biallelically expressed gene have no major impact on carcinogenesis. The prevalence of somatic mutations in malignancies is low. Gene rearrangements involving cdknlA are scarce. CDKN1A is expressed in both premalignant and malignant lesions. While the prognostic value of nuclear CDKN1A expression is controversial, the prognostic value of its recently discovered cytoplasmic accumulation is simply unknown. CDKN1A translocates from the nucleus to the cytoplasm when cleaved by caspase-like activities during early apoptosis. The presence of cytoplasmic catabolites (e.g.: p14) might therefore indicate apoptosis. We found no correlation between nuclear and cytoplasmic anti-CDKN1A immunoreactivity in our samples of oropharyngeal squamous cell carcinoma. CDKN1A Cap20, CDKN1, CDKN1A, CDKNA1, Cip-1, Mda-6, P21, Pic1, Sdi-1, Waf-1.