Diagnostics and therapy of bilateral choanal atresia in association with CHARGE syndrome.

BACKGROUND: Bilateral choanal atresia in patients with CHARGE syndrome becomes symptomatic immediately after birth. A prompt diagnosis, the implementation of sufficient preliminary measures, and the delivery of surgical therapy are crucial. This article is intended to assist in terms of diagnostics and a therapy recommendation. METHODS: We performed a retrospective study using the medical records of all newborns in the University Hospital in Bonn, diagnosed with bilateral choanal atresia and CHARGE syndrome and underwent surgery at the Department of Otorhinolaryngology, Head and Neck Surgery. RESULTS: A total of 21 patients have been treated with a unilateral or bilateral choanal atresia. 14 patients were primarily treated with transnasal endoscopy or underwent transnasal endoscopic surgery as a follow-up intervention (73.68%). Nine patients had a syndromal appearance, which was considered a definite diagnosis in six patients (five with CHARGE syndrome). All five patients with CHARGE syndrome received transnasal endoscopic treatment and a stent was inserted. DISCUSSION: Bilateral choanal atresia can be a life-threatening situation requiring acute measures. The therapeutic trend goes towards transnasal endoscopic resection. Primary intervention should be: minimally invasive, one-stage surgery, functional, and associated with low complication rates. Patency can be increased by saline irrigations, topical corticosteroids, endoscopic controls, and regular dilatation. The insertion of stents is controversially discussed but can be useful in syndromal patients. However, adjuvant therapy with a stent and mitomycin C is increasingly being abandoned. A significantly higher recurrence rate must be expected in association with CHARGE syndrome. Stenting should be considered on an individual basis. Continuous training and support of the parents are obligatory.

[Guideline on diagnosis, treatment, and follow-up of laryngeal cancer]. / S3-Leitlinie Diagnostik, Therapie und Nachsorge des Larynxkarzinoms.

The German S3 guideline on diagnosis, treatment, and follow-up of laryngeal cancer was developed in 2019 as part of the oncology guideline program of the Association of the Scientific Medical Societies in Germany (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften, AWMF) of the German Cancer Society (Deutsche Krebsgesellschaft, DKG) and German Cancer Aid (Deutsche Krebshilfe, DKH), published under the leadership of the German Society for Otorhinolaryngology, Head and Neck Surgery. The guideline was funded by DKH as part of the oncology guideline program. Since guidelines are an important tool for quality assurance and quality management in oncology, they should be incorporated into everyday care in a targeted and sustainable manner. The guideline should generally fulfil the interdisciplinary character of early diagnosis, diagnostics, treatment, rehabilitation, and follow-up, with the aim of developing evidence- and consensus-based recommendations and statements for treatment of laryngeal cancer with the aim of organ preservation, but also show their limits. The main recommendations of the original text are summarized. The guideline is available as a long and a short version in the guideline program of the DKG ( https://www.leitlinienprogramm-onkologie.de/leitlinien/larynxkarzinom/ ) and also as an app ( https://www.leitlinienprogramm-onkologie.de/app/ ).

[Guideline on diagnosis, treatment, and follow-up of laryngeal cancer]. / S3-Leitlinie Diagnostik, Therapie und Nachsorge des Larynxkarzinoms.

The German S3 guideline on diagnosis, treatment, and follow-up of laryngeal cancer was developed in 2019 as part of the oncology guideline program of the Association of the Scientific Medical Societies in Germany (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften, AWMF) of the German Cancer Society (Deutsche Krebsgesellschaft, DKG) and German Cancer Aid (Deutsche Krebshilfe, DKH), published under the leadership of the German Society for Otorhinolaryngology, Head and Neck Surgery. The guideline was funded by DKH as part of the oncology guideline program. Since guidelines are an important tool for quality assurance and quality management in oncology, they should be incorporated into everyday care in a targeted and sustainable manner. The guideline should generally fulfil the interdisciplinary character of early diagnosis, diagnostics, treatment, rehabilitation, and follow-up, with the aim of developing evidence- and consensus-based recommendations and statements for treatment of laryngeal cancer with the aim of organ preservation, but also show their limits. The main recommendations of the original text are summarized. The guideline is available as a long and a short version in the guideline program of the DKG ( https://www.leitlinienprogramm-onkologie.de/leitlinien/larynxkarzinom/ ) and also as an app ( https://www.leitlinienprogramm-onkologie.de/app/ ).

[Surgical therapy of oropharyngeal cancer-state of the art]. / Operative Behandlung des Oropharynxkarzinoms ­ Stand der Technik.

Surgical therapy, regardless of the procedure, remains of great importance for today's treatment of oropharyngeal carcinomas, despite advances in radiation and immunotherapy. The individual treatment plan should be defined in discussion with the patient and in an interdisciplinary tumor conference, taking into account the likelihood of achieving of tumor-free resection margins and an acceptable postoperative quality of life. With regard to conventional and possibly also open surgical procedures, a good overview of the surgical site-particularly in the case of more extensive carcinomas and challenging patient anatomy-and simplified reconstructability of the defect region are decisive aspects. Endoscopically, microsurgically, or even robot-assisted minimally invasive procedures have the advantage of precise and gentle removal of tumor tissue with improved maintenance of function. Overall, selection of the appropriate surgical procedure remains an individual decision based on tumor size, the facilities at the tumor center, and the surgeon's experience. The extent of surgical intervention, also with regard to simultaneous neck dissection, depends on tumor stage. In the case of oropharyngeal carcinomas, there will be an increasing distinction between human papillomavirus (HPV)-negative and HPV-positive tumors in the future; however, the therapeutic strategy is currently identical. Upcoming clinical trials will show whether treatment de-escalation is appropriate depending on HPV infection status.

[Prognostic and predictive methylation biomarkers in HNSCC : Epigenomic diagnostics for head and neck squamous cell carcinoma (HNSCC)]. / Prognostische und prädiktive Methylierungsbiomarker für HNSCC : Epigenomische Diagnostika für Plattenepithelkarzinome des Kopf- und Halsbereichs (HNSCC).

BACKGROUND: Prognostic and predictive biomarkers for personalized treatment management in head and neck squamous cell carcinoma (HNSCC) are of great clinical interest. OBJECTIVE: DNA methylation is an epigenetic process involved in gene regulation and could be a source of potential prognostic and predictive biomarkers. METHODS: This study comprises literature research in PubMed and own studies. RESULTS: Gene methylation, e.g. of PITX2, is a strong, human papillomavirus (HPV)-independent prognostic biomarker. SHOX2 and SEPT9 methylation in circulating cell-free DNA within blood plasma correlates with tumor stage and prognosis. Methylation of diverse immune checkpoints, e.g., PD­1, PD-L1, and CTLA4, is also prognostic and correlates with gene expression. CONCLUSION: DNA methylation is a source of efficient prognostic blood plasma- and tissue-based biomarkers. However, prior to clinical implementation, studies must prove that biomarker-guided treatment selection can lead to better outcomes or reduced toxicity. The applicability of DNA methylation as a predictive biomarker for targeted drug-based cancer therapy seems promising, although further validation is needed.

[Social reimbursement-the Spanish-German ENT Society's (SDGHNO) Latin America project]. / Soziale Rückvergütung ­ das Projekt "Lateinamerika" der Spanisch-Deutschen HNO-Gesellschaft (SDGHNO).

Nowadays, social projects are usually oriented in such a way that after a given period of time, they can either support themselves independently or even allow a pecuniary reimbursement. In the latter case, experts speak of a profit-oriented reimbursement. On the other hand, there is so-called social reimbursement, which in contrast to the abovementioned form is not profit oriented, but, for example, considers its task fulfilled by the fact of successful knowledge transfer. The Spanish-German Society for ENT Medicine and Head and Neck Surgery (SDGHNO) launched the Latin America project in 2001 under the patronage of the then President Prof. Dr. Wolfgang Draf (Fulda). The goal of the SDGHNO was and is to create a professional as well as cultural platform for Spanish- and German-speaking ENT doctors. This platform can and should be used for professional purposes, e.g., for knowledge transfer. Since the beginning of its existence, the Latin America project has thus brought numerous scientific events into being and created specific contacts which have lasted until today or have even been continued and further developed. Particularly successful examples are Chile, Colombia, and Peru. This is a vivid example of social reimbursement, because the participating German-speaking members/speakers carried out their tasks on an entirely voluntary basis. Thus, the SDGHNO did not bear any travel, catering, or accommodation costs. The activities of the SDGHNO within the framework of the Latin America project are explained.

[Interventional radiology in the head and neck region]. / Interventionelle Radiologie im Kopf-Hals-Bereich.

In interventional neuroradiology, endovascular embolization represents an important and helpful tool in the treatment of multiple head and neck diseases. These interventional procedures may be performed with curative intent, to reduce the surgical risk within a multimodal treatment concept, or to improve or at least maintain a good quality of life within a palliative therapy concept. In addition to a good understanding of disease pathology, knowledge of vascular anatomy, including collateral vessels and dangerous extracranial-intracranial anastomoses, is essential for successful treatment, as is implementation of an established technique using appropriate material. Indications for endovascular embolization are i. otherwise unmanageable bleeding (caused by e. g., trauma, vascular malformation, or tumor), ii. reduction of perioperative bleeding by preoperative embolization in case of a hypervascularized tumor, iii. selective induction of tumor necrosis by palliative embolization to enhance local tumor control. Major complications such as stroke, loss of vision, and cranial nerve palsy are mostly due to a lack of preinterventional evaluation. Regarding neurological deficits, interventions within the supply region of the external carotid artery have a complication rate below 1%.

[PET-CT in head and neck cancer]. / PET-CT bei Karzinomen im Kopf­Hals­Bereich.

The importance of 18F-fluorodesoxyglucose positron-emission tomography (FDG-PET) for the diagnosis of malignant disease is increasing. On one hand, this is due to the high sensitivity of this method, on the other, because the entire body can be examined. FDG-PET can be particularly advantageous for the diagnosis of head and neck tumors, where tumor staging is an important prognostic parameter and essentially determines the therapeutic regimen. This article presents the different possibilities for combined evaluation with PET and computed tomography (CT) for the diagnosis of patients with head and neck cancer. Special focus is placed on primary staging and tumor follow-up, as well as on the role of PET-CT in the diagnosis of patients with cancer of unknown primary origin (CUP). The use of PET-CT for radiotherapy planning and new aspects of PET technology are also discussed.

[Imaging for surgical planning : Tumor surgery including reconstructive procedures]. / Bildgebung zur Operationsplanung : Tumoroperationen einschließlich rekonstruktiver Verfahren.

Alongside clinical investigation, imaging is an important diagnostic modality for guiding treatment decisions and particularly for surgical planning in head and neck cancer. The significance and type of imaging depends on localization of the primary tumor. Beside the primary tumor, each imaging procedure must also include the lymph nodes, in order to develop an overall concept of surgical treatment. In addition to the superficial growth of a tumor, it is of utmost importance that its infiltration also be detected by imaging, in order to define the extent of tumor resection and identify potentially necessary reconstructive procedures. The type of imaging needed to understand tumor localization and size, e.g., CT or MRI, depends on the region. In some cases the methods are complementary.

[Diagnosis and treatment of parapharyngeal space tumors]. / Therapie parapharyngealer Tumoren.

The parapharyngeal space extends from the nasopharynx to the oropharynx. It is bordered medially by the pharyngeal wall and the constrictor pharyngis muscles, and laterally by the mandible. One distinguishes between a pre- and a poststyloid space. Tumors of the parapharyngeal space are rare and represent less than 1 % of all head and neck neoplasms. Benign (70-80 %) as well as malignant (20-30 %) tumors arise from different structures of the parapharyngeal space, mainly from salivary glands and nerve structures. Concerning salivary gland tumors, most are pleomorphic adenomas typically appearing in the prestyloid space, whereas the schwannomas that may also arise are located in the poststyloid space. The main symptom is dysphagia, with the tumor generally presenting as a visible bulking of the pharyngeal wall, in rare cases also as an externally visible cervical mass. Treatment is generally surgical resection, particularly in benign tumors, preferably via transcervical access. If R0 resection of malignancies is possible, this should be performed. In malignant lymphomas and nonresectable tumors, primary chemo-, radio-, or combination therapy should be considered after histologic confirmation. For neurogenic tumors, particularly vagal nerve schwannoma and especially in older patients, a wait-and-scan strategy is most favorable, since postoperative vagal palsy is unavoidable with surgical resection. Treatment planning for parapharyngeal space tumors requires good knowledge of topographic anatomy and careful evaluation of imaging findings.

Different tissue distribution properties for glycosylation variants of fusion proteins containing the p40 subunit of murine interleukin-12.

Antibody-based fusion proteins are gaining increasing importance for therapeutic applications, but the impact of glycosylation on in vivo biopharmaceutical performance is not always completely understood. In this article, we have analyzed biochemical and pharmaceutical properties of fusion proteins, consisting of the F8 antibody (specific to the EDA domain of fibronectin, a marker of tissue remodeling and of angiogenesis) and of the p40 subunit of interleukin-12, an inhibitor of inflammation. The corresponding fusion protein (F8-IL12p40), which inhibits colitis development in mice, is a glycosylated protein with suboptimal disease targeting properties in vivo Since the protein was extensively glycosylated, as evidenced by PNGase F treatment and mass spectrometric analysis, we mutated four asparagine residues in various combinations. The corresponding proteins exhibited similar biochemical and antigen-binding properties, but differences in thermal stability and bioactivity. Asparagine mutations did not lead to recovery of disease targeting performance in vivo, as evidenced by quantitative biodistribution studies with radioiodinated protein preparations in tumor-bearing mice. By contrast, an almost complete recovery of targeting was achieved with an enzymatically deglycosylated protein preparation. These findings reinforce the concept that different glycostructures can have an impact on tissue distribution properties.

[Early recognition of cancerous lesions in the mouth and oropharynx: Automated evaluation of hyperspectral image stacks]. / Früherkennung kanzeröser Läsionen in Oropharynx und Mundhöhle: Automatisierte Evaluation hyperspektraler Bildstapel.

BACKGROUND: Early detection of cancerous lesions is still crucial for a patient's prognosis. Although diagnostic access to the oral cavity and oropharynx is comparably easy, the incidence of resulting disease remains high. This is due to the fact that in many cases, malignity is recognized too late on a purely visual basis. Previously, we discussed the application of hyperspectral imaging for early detection of precancerous and cancerous lesions of the larynx. This time, we evaluate the method in the oral cavity and oropharynx. MATERIALS AND METHODS: In 85 patients scheduled for endoscopy, hyperspectral imaging was performed. We used a rigid 0-degree endoscope, a light-adjustable monochromator, and a hyperspectral camera. For evaluation of the method, 3 patients were chosen exemplarily. Training sites from physiological and cancerous tissues were marked. Hyperspectral data from 1 patient were used to train a classifier, which was then used for automatic detection of precancerous and cancerous lesions in another 2 patients. RESULTS: Intraoperative hyperspectral imaging was performed without any problems. Classification showed sensitivities of 61 and 43%, and a specificity of 100%. CONCLUSION: This proof-of-concept study underscores the high potential of hyperspectral imaging for early recognition of cancer in the mouth and oropharynx. Besides a better prognosis for cancer patients, this approach could lead to higher cost efficiency in the health system.

[Evaluation and Optimization of Microvascular Arterial Anastomoses by Transit Time Flow Measurement]. / Evaluation und Optimierung arterieller Anastomosen durch Transit-Zeit Flussvolumenmessungen.

UNLABELLED: INDRODUCTION: The regular application of transit time flow measurement in microvascular anastomoses during heart surgery has lead to improvements of the outcome of coronary artery bypass grafts. Our study was meant to discover whether this measurement method was also applicable for evaluation and optimization of microvascular arterial anastomoses of radial forearm flaps. METHODS: In this prospective examination a combining ultrasound imaging and transit time flow measurement device (VeriQ, MediStim) was used during surgery to assess anastomotic quality of 15 radial forearm flaps. Pulsatility index (PI) and mean blood flow were measured immediately after opening the arterial anastomosis as well as 15 min afterwards. Furthermore, application time and description of handling were recorded seperately for every assessment. RESULTS: Mean blood flow immediately after opening the anastomosis and 15 min later were 3.9 and 3.4 ml/min resepectively showing no statistically significant difference (p=0.96). There was no significance in the increase of pulsatility index from 22.1 to 27.2 (p=0.09) during the same time range, either. Due to measurement results showing atypical pulse curves in 2 cases decision for surgical revision of the anastomoses was made. All forearm flaps showed good vascularisation during follow-up. Time for device set up, probe placement and measurements was about 20 min. Handling was described to be uncomplicated without exception. There were no noteworthy problems. CONCLUSION: Transit time flow measurement contributes to the improvement of anastomotic quality and therefore to the overall outcome of radial forearm flaps. The examined measurement method provides objective results and is useful for documentation purposes.

[Change of Taste during and after IM- /IG-Radiotherapy for Head and Neck Cancer Patients]. / Veränderungen des Schmeckvermögens durch IM-/IG-Strahlentherapie bei Kopf-Hals-Tumorpatienten.

OBJECTIVE: Taste dysfunction is a common side effect during irradiation of head and neck. Our aim was to determine the time-dependent course and a possible dependency of this side effect to the radiation-dose during irradiation with helical tomotherapy. PATIENTS AND METHODS: 31 patients with malignant tumours in the region of head and neck received an IG-/IM-radiotherapy (helical tomotherapy).The median total dose was 63 Gy (range 30-66 Gy). For all patients the subjective taste dysfunction was documented and correlated to the median (D50) tongue dose. RESULTS: A subjective taste dysfunction was registered by the patients themselves after 9 BT (days of radiotherapy) (median). This correlates to a mean dose (D50) of 15.3 Gy (back third of tongue (back ZD)), 11.3 Gy (middle ZD), 8.2 Gy (front ZD). A subjective ageusia occurred after 15 BT (median) (28.9 Gy (back ZD), 22.2 Gy (middle ZD), 17.7 Gy (front ZD)). A starting recovery was registered by 77% of the patients in the first 6-8 weeks after the end of radiotherapy. CONCLUSION: The time-dependent course of taste dysfunction during radiotherapy and the following recovery is predictable. A dependency of taste dysfunction to radiation-dose exists. Based on the collected data a targeted dose reduction to the tongue with a view to minimize the taste dysfunction is thinkable and aim of further studies.

[Management of atypical cervical mycobacteriosis in childhood]. / Management der zervikalen atypischen Mykobakteriose im Kindesalter.

Atypical mycobacteriosis is a rare cause of cervical lymphadenitis that most frequently affects immunoincompetent children between the ages of 12 months and 5 years. The typical clinical manifestation is a painless unilateral cervical mass. The nonspecific clinical symptoms and laboratory parameters complicate diagnosis and, therefore, therapeutic management. Various therapeutic options, including surgery, antimycobacterial drug therapy and wait-and-scan approaches are discussed in the literature. Complete surgical excision has become the established treatment of choice. However, controlled randomized studies that clearly demonstrate the benefits of a particular type of therapy are lacking.

Incidence and localization of abnormal mucosa findings in patients consulting ENT outpatient clinics and data analysis of a cancer registry.

For patients without symptoms and at risk, there is no established early detection program to discover carcinomas of the upper aerodigestive tract in the sense of secondary prevention. Such type of prevention seems even more desirable because the chances for a cure and the quality of life are strongly dependent on the stage of the tumor and the time of the initial diagnosis. Six hundred and eight patients without symptoms but at least one of the self-reported risk factors "smoking", "alcohol consumption" or "reflux" were examined with an endoscope or an optical microscope for pathological findings in the upper aerodigestive tract once a year. In addition, the incidence of malignancies of the upper aerodigestive tract between 2001 and 2010 was determined through the Cancer Registry of Schleswig-Holstein. Tissue samples were taken from 18 of the 608 patients. Eleven patients (1.8%) had a squamous cell carcinoma. Another patient suffered from non-Hodgkin's lymphoma and one from larynx tuberculosis. The ratio of detected malignancies in the oral cavity and the oropharynx on the one hand and the hypopharynx and larynx, which can only be examined by endoscopes, on the other hand were in our cohorts and in our survey according to the cancer registry was 5/6. The above-described methods allow examining risk patients easily and safely. According to current publications, the ratio of the found malignancies exceeds the expected ratio significantly, which presumably was caused by the examination targeting patients at risk. Due to the expanded examination area using optical instruments more than doubles the rate of discoverable malignancies compared to the limitations posed by the examination of directly visible areas of the oral cavity of the oropharynx.