[Functional outcome after transmandibular resection and primary chemoradiation in advanced oropharyngeal squamous cell carcinoma]. / Funktionelle Ergebnisse nach transmandibulärer Resektion und primärer Radiochemotherapie bei fortgeschrittenen Kopf-Hals-Plattenepithelkarzinomen.

OBJECTIVE: The aim of this study was to assess the functional outcome after transmandibular resection and reconstruction via a radial forearm flap (TMR+RFF) compared to primary chemoradiotherapy (pCRT) in advanced oropharyngeal squamous cell carcinoma (OPSCC). METHODS: The study compared 50 OPSCC patients treated with TMR+RFF to 50 OPSCC patients receiving pCRT. The time taken to swallow water served as the primary endpoint. The Saxon test, maxillomandibular distance, Mallampati score, ratio of height to weight, nasal penetration, tracheostomy/gastral tube requirement, and four validated questionnaires (visual analog scale for xerostomia, Sicca VAS; MD Anderson Dysphagia Inventory, MDADI; Voice Handicap Index, VHI; European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Head and Neck Cancer, 35 items, QLQ-H&N35) were applied to access functionality and quality of life. RESULTS: Patients after TMR+RFF showed an increased rate of nasal penetration (p < 0.0001), which was associated with a longer water swallowing time (p < 0.05). A modified reconstruction of the soft palate significantly decreased the rate of nasal penetration in comparison to classical reconstruction (p = 0.0001). Patients with pCRT suffered significantly more xerostomia (Saxon test) than patients with TMR+RFF and adjuvant therapy. None of the subjective questionnaires revealed significant differences between the groups. CONCLUSION: TMR+RFF with modified reconstruction and adjuvant treatment and pCRT showed comparable functional outcomes.

[Stomal Cancer Recurrency, A Clinic-Pathological Consideration]. / Stomarezidive, eine klinisch-pathologische Betrachtung.

Objectives: Analysis of pre-operative tracheostomy and circumjacent tumour free margins as risk factors in the development of stomal recurrent disease after (pharyngo)laryngectomy. Material and Methods: 124 patients after (pharyngo)laryngectomy were analyzed for disease related data and tumour samples were analyzed for tumour free margins. The overall cohort was divided into patients with/withour pre-operative tracheostomy. Results: 18 patients suffered from recurrent disease (10 stomal, 8 distant metastases). Advanced T-status, female gender, and sub-/glottic tumour manifestation resulted in a higher rate of prior tracheostomy. Pre-operative tracheostomy did not influence the development of stomal recurrency. R0 resection was achieved in 94% of our patients, with significant reduced tumour free margins in patients with stomal recurrency (p=0.002) Conclusion: Pre-operative tracheostomy did not influence the development of stomal recurrent disease. The clinical identification of ventral soft tissue infiltration should result in extensive surgical concepts.

[Current surgical and adjuvant therapy concepts of malignant tumors of the facial skin and the pinna]. / Aktueller Stand der chirurgischen und adjuvanten Therapie der Malignome der Gesichtshaut und der Ohrmuschel.

Malignant tumors of the skin had been a rare entity 2 decades ago. Today they are spread rapidly worldwide. Malignant neoplasms of the skin, the largest human organ, may occur from all structures and layers. While previously skin cancer -occurred mainly after the age of 60, the incidence increases now in younger ages. Strong sunburns in the childhood and before the age of 20 are important risk factors for the development of malignancies of the skin. An increased exposure to UV rays is found especially in the facial skin, where basal cell carcinoma, squamous cell carcinoma, malignant melanoma and Merkel cell carcinomas are the most common malignancies. Early diagnosis of malignancies and therapy-oriented mostly surgical approaches are crucial for the prognosis of all skin cancers. Therefore under the aspect of the increasing incidence these topics will be pointed out according to the latest findings including current multimodal therapy concepts and future treatment options.

Which kind of frontal mandibulotomy is the smartest? A biomechanical study.

PURPOSE: Retrospective clinical evaluation and biomechanical tests were performed to compare the primary stability and the rate of pseudarthrosis formation after irradiation for two types of mandibular split osteotomies: the stairstep osteotomy (SSO) and the straight-line osteotomy (SLO). METHODS: The postoperative occurrence of pseudarthrosis was retrospectively analysed in 46 non-consecutive clinical cases of SSO and SLO between 2003 and 2013. Biomechanical tests were performed on 12 standardised synthetic mandibles (Synbone) to compare the SSO and SLO approaches. Two 2.0 mm monocortical miniplates (Medartis) were used for osteosynthesis. The artificial mandible specimens were loaded to 300 N on the Mandibulator test bench while interfragmentary motion was measured using the PONTOS optical measurement device. RESULTS: The retrospective clinical analysis showed a rate of pseudarthrosis of 19% in the SLO group versus only 5% in the SSO group (p = 0.17). In the biomechanical investigation, the average interfragmentary movement was 14.3 ± 7.70 for the SLO group and 4.57 ± 2.33 for the SSO group under a maximum load of 300 N, resulting in a statistically significant difference between the two approaches (p = 0.014). CONCLUSION: To minimise the rate of postoperative pseudarthrosis formation, SSO is superior to SLO for mandibular split procedures, because SSO provides greater resistance to vertical loads and allows less interfragmentary movement. LEVEL OF EVIDENCE: 2C (Outcomes research).

In vitro chemosensitivity of head and neck cancer cell lines.

BACKGROUND: Systemic treatment of head and neck squamous cell carcinoma (HNSCC) includes a variety of antineoplastic drugs. However, drug-resistance interferes with the effectiveness of chemotherapy. Preclinical testing models are needed in order to develop approaches to overcome chemoresistance. - METHODS: Ten human cell lines were obtained from HNSCC, including one with experimentally-induced cisplatin resistance. Inhibition of cell growth by seven chemotherapeutic agents (cisplatin, carboplatin, 5- fluorouracil, methotrexate, bleomycin, vincristin, and paclitaxel) was measured using metabolic MTT-uptake assay and correlated to clinically-achievable plasma concentrations. - RESULTS: All drugs inhibited cell growth in a concentration-dependent manner with an IC50 comparable to that achievable in vivo. However, response curves for methotrexate were unsatisfactory and for paclitaxel, the solubilizer cremophor EL was toxic. Cross-resistance was observed between cisplatin and carboplatin. - CONCLUSION: Chemosensitivity of HNSCC cell lines can be determined using the MTT-uptake assay. For DNA-interfering cytostatics and vinca alkaloids this is a simple and reproducible procedure. Determined in vitro chemosensitivity serves as a baseline for further experimental approaches aiming to modulate chemoresistance in HNSCC with potential clinical significance.

[Emergency management of acute angioedema]. / Notfallsituation akutes Angioödem.

Angioedema is an oedematous swelling of the mucosa or submucosa of the skin. Acute angioedema represents a clinical emergency when the pharynx or larynx are involved and breathing of the patient is impaired. For rapid and effective treatment it is necessary to differentiate between allergic and non-allergic angioedema. Three of the five subforms of non-allergic angioedema are mediated by bradykinin: renin-angiotensin-aldosterone system (RAAS)-blocker-induced angioedema (RAE), hereditary angioedema (HAE) and acquired angioedema (AAE). Antihistamines, corticosteroids and adrenalin can be used to treat allergic angioedema but are ineffective in acute attacks of non-allergic angioedema. In these events the bradykinin-B2-receptor antagonist icatibant (in HAE, or RAE) or C1-INH concentrate (in HAE, or AAE) are therapeutic options for rapid alleviation of acute angioedema. The following article gives an overview of the diagnostics and treatment in the emergency situation of "acute angioedema", especially if swelling of the head-and-neck region is present.

[Risk of hemorrhage after adenoidectomy and tonsillectomy. Value of the preoperative determination of partial thromboplastin time, prothrombin time and platelet count]. / Risiko von Blutungen nach Adenotomie und Tonsillektomie. Aussagekraft der präoperativen Bestimmung von PTT, Quick und Thrombozytenzahl.

BACKGROUND: Hemorrhage after tonsillectomy and adenoidectomy remains a serious complication. Therefore, routine preoperative coagulation screening, including activated partial thromboplastin time (aPTT), prothrombin time (PT) and platelet count (PLC), are regularly performed, also for medicolegal reasons. In the recently published statement of the German Society of Otorhinolaryngology, Head and Neck Surgery the need for routine preoperative coagulation screening is discussed, but so far no standardized procedure had been established. According to this statement - at least for children - routine preoperative coagulation screening is not mandatory as long as the thorough medical history provides no evidence for a coagulation disorder ( http://www.hno.org/kollegen/gerinnung_te_ae.html ). The present study was undertaken to determine the occurrence of postoperative hemorrhage on the one hand, and the incidence of abnormal preoperative routine coagulation parameters or pathological anamnesis findings on the other. PATIENTS AND METHODS: In 688 patients, a standardized clinical history was obtained using a questionnaire. Coagulation screening included aPTT, PT, and PLC was also carried out. Bleeding complications were then correlated with anamnesis features and abnormalities in coagulation screening. RESULTS: In 39 (5.7%) of the 688 patients we found abnormal coagulation values, which were confirmed in repeated analyses. In six of these a detailed analysis revealed occult coagulation disorders requiring correction only in the case of bleeding complications who were previously unknown. Fifteen patients were already known to have a coagulation disorder, and the anamnesis identified no additional patient at risk. Thus, 21 patients with coagulation disorders requiring correction in the case of a bleeding complication underwent surgery. However, only eight (38%) of these showed abnormal routine coagulation parameters. Surgical treatment of postoperative hemorrhage was required in 12 patients, all of whom had normal values for aPTT, PT and PLC. CONCLUSION: The frequently performed determination of routine coagulation parameters (aPTT, PT, PLC) is not able to reliably identify relevant coagulation disorders or to predict the risk for postoperative hemorrhagic complications after adenoidectomy or tonsillectomy.

[ACE-inhibitor induced angioedema]. / Das ACE-Hemmer-induzierte Angioödem.

ACE-inhibitor induced angioedema is a non-allergic drug-related side effect. Inhibited bradykinin degradation leads to an unphysiological enhanced bradykinin plasma level with vascular leakage and, consequently, to angioedema. ACE-inhibitor induced angioedema develop rapidly in the head and neck region. Typical sites of manifestation are lips, tongue, and larynx. Novel pharmacotherapies may allow a causal treatment of the ACE-inhibitor induced angioedema in the future.

Preoperative screening for coagulation disorders in children undergoing adenoidectomy (AT) and tonsillectomy (TE): does it prevent bleeding complications?

BACKGROUND: Bleeding remains the most important complication of adenotonsillectomy in children. Preoperative coagulation tests are widely used to detect unknown bleeding disorders. To determine the efficacy of preoperative coagulation screening in preventing bleeding complications. PATIENTS: Study group 1: 148 healthy children referred by the otorhinolaryngology department for preoperative pediatric examination. Study group 2: 124 healthy children sent to the hemostaseologic clinic for preoperative investigation of a prolonged PTT. METHOD: The incidence of relevant coagulation disorders detected by a standardized bleeding history and coagulation screening tests was studied prospectively in 2 study groups planned for AT and/or TE. The frequency of abnormal bleeding was investigated retrospectively in those children who underwent surgery. RESULTS: Bleeding disorders were detected in 7/148 and 15/124 children in study group 1 and 2 respectively. 141/148 and 79/124 children actually underwent surgery, 62 TE +/- AT + 79 AT alone and 26 TE +/- AT + 53 AT alone respectively. Major bleeding occurred in 1/141 patients (1 TE) in study group 1. Preoperatively, this child had shown normal coagulation screening tests. In 4/79 patients (3 TE, 1 AT) in study group 2, surgery was complicated by major bleeding. Despite extensive testing, no relevant bleeding disorder had been diagnosed in these children preoperatively. Sensitivity of coagulation screening tests for major bleeding was 0 in study group 1. CONCLUSIONS: In our study, coagulation screening failed to effectively identify patients at risk of bleeding.

[Collagen injection for augmentation of periprosthetic leakage after tracheo-esophageal voice restoration]. / Die Kollageninjektion zur Augmentation des insuffizienten Stimmprothesenlagers.

After laryngectomy the majority of patients receive a vocal rehabilitation by tracheo-esophageal puncture and insertion of voice prosthesis. Periprosthetic leakage causing aspiration represents a well known complication and is frequently treated by temporary removal of the prosthesis with shrinkage of the shunt. Here we describe 10 patients with such a leakage treated by collagen injection for periprosthetic tissue augmentation. A mean of 1,6 injections were necessary for complete control of the leakage. The injection was well tolerated and was found effective for median period of 9,3 months. In our hands the periprosthetic collagen injection represents an effective and well tolerated procedure for temporary augmentation of tracheo-esophageal leakage in post-laryngectomy patients. However, alternative fillers without pre-testing necessity and longer augmentation intervals should be considered.

[The subclavicular route for the pectoralis major myocutaneous flap]. / Der infraklavikuläre Durchzug des M.-pectoralis-major-Lappens.

BACKGROUND: The pectoralis major myocutaneous flap (PMMF) is an important reconstructive tool for lesions in the head and neck region. Using the supraclavicular route, the PMMF reliably transfers large amounts of well-vascularized skin and muscle into defects of the upper aerodigestive tract. However, limited length and arc of rotation as well as excessive bulk can be problematic. PATIENTS AND METHODS: In the current study, these problems have been addressed by passing the pedicle deeply to the clavicle. Following flap harvest, the pedicle was passed in the subclavicular plane in 15 head and neck cancer patients for primary and secondary reconstruction. RESULTS: Using this route it was possible to increase the medium length of PMMF to 3 cm compared to the supraclavicular route. No total flap necrosis occurred, however, temporary complications were observed in three of 15 cases (20%)--partial flap necrosis occurred in two cases and fistula formation was observed in one case. This rate is in accordance with complication rates described for the supraclavicular route. However, in long-term follow-ups we observed a fracture of the clavicle in two patients in whom, in contrast to the others, the periostium was not only prepared posteriorly but over the whole circumference. CONCLUSIONS: The subclavicular route for PMMF increases the length and arc of rotation available for reconstruction without compromising vascular supply to a higher degree than with the conventional supraclavicular route. Furthermore, this concept decreases the bulk of the PMMF pedicle which is functionally and cosmetically favourable. Thus, the subclavicular route of PMMF is safe and allows an extension of the reconstructive possibilities.

[Dapsone-induced agranulocytosis. The role of xenobiotic-metabolizing enzymes demonstrated by a case report]. / Dapson-induzierte Agranulozytose. Die Rolle fremdstoffmetabolisierender Enzyme am Beispiel einer Kasuistik.

A 34-year-old female patient with a three year history of generalized granuloma annulare was treated systemically with dapsone (DADPS). Six weeks after the onset of treatment, the patient developed an extensive tonsillitis of the base of the tongue with fever and malaise. Routine laboratory work showed a leukocytopenia with agranulocytosis. Further investigation revealed a marked decrease of the enzyme activity of N-acetyltransferase 2, which plays an important role in dapsone metabolism. Treatment included the cessation of dapsone, antibiotic coverage, and G-CSF leading to the rapid improvement of symptoms and normalization of leukocyte counts. Dapsone-induced angina agranulocytotica is a rare event and is interpreted as an idiosyncratic reaction. Depending on genetic polymorphisms of various enzymes, dapsone can be metabolized to immunologically or toxicologically relevant intermediates. Because of the risk of severe hematologic reactions, dapsone should only be employed for solid indications and with appropriate monitoring.

[Squamous cell carcinoma of the head and neck. Principles and current concepts of immunotherapy]. / Plattenepithelkarzinome des Kopf-Hals-Bereichs. Grundlagen und aktuelle Konzepte der Immuntherapie.

Biologic therapies able to induce or up-regulate anti-tumor immune responses could represent a complementary approach to improve the conventional treatment of squamous cell carcinomas of the head and neck (SCCHN). Patients with SCCHN are frequently immunocompromised due to the elimination and dysfunction of critical immune effector cells. Therefore, it might be necessary to restore these immune functions to allow for the generation of effective anti-tumor host responses. Simultaneously, to prevent tumor escape from immunological recognition and destruction, it might also be necessary to alter antigenic and immunogenic attributes of the malignant cells. The present overview summarizes general aspects, historical data, and recent advances in the field of immunotherapy of SCCHN, including non-specific immune stimulation, transfer of immunocompetent cells, gene therapy, use of monoclonal antibodies, and anti-cancer vaccines.

Increased C-reactive protein in ACE-inhibitor-induced angioedema.

AIMS: This study was designed to identify new factors which may contribute to angiotensin-converting-enzyme-inhibitor (ACEI)-induced angioedema. METHODS: In a retrospective cohort study we examined 25 patients who used an ACEI and presented at our emergency room with acute angioedema as well as 18 patients with unknown cause of angioedema and a total of 21 patients on ACEI-therapy without previous angioedema. We measured markers of inflammation such as acute-phase proteins (C-reactive protein, fibrinogen), leukocyte count and body temperature. RESULTS: The mean interval between initiation of ACEI treatment and first manifestation of angioedema was 35.8 +/- 5.3 months. During symptomatic angioedema, mean plasma levels of C-reactive protein and fibrinogen were significantly increased by 7.3-fold and 1.5-fold, respectively, while leukocyte count and body temperature were normal. These changes disappeared after successful treatment of angioedema and were not found in patients with angioedema of unknown cause and those receiving ACEI without having experienced angioedema. CONCLUSION: Our findings demonstrate for the first time that ACEI-induced angioedema is associated with strongly increased plasma levels of CRP. We suggest that CRP is involved in the pathophysiology of ACEI-induced angioedema.

[ACE inhibitor-induced angioedema in the head and neck region. A matter of time?]. / Durch ACE-Hemmer induziertes Angioödem des Kopf-Hals-Bereichs. Eine Frage der Zeit?

BACKGROUND: Angioedema in the head and neck region is potentially life-threatening and may occur as a side effect of inhibitors of the angiotensin-converting-enzyme (ACEI). So far, little is known about the time between the first application of ACEI and the occurrence of angioedema, or of possible cofactors and laboratory changes. MATERIAL AND METHODS: A total of 21 patients with angioedema during the course of ACEI treatment were compared to 11 patients with angioedema of unknown cause. These were retrospectively analysed for the following criteria: (1) duration of ACEI medication, (2) leading and concomitant diseases, (3) history of allergies, (4) co-medication, (5) laboratory changes, (6) treatment success, and (7) manifestation of recurrent episodes. RESULTS: The mean interval between the initiation of ACEI therapy and the first occurrence of angioedema exceeded 2 years. Values for the acute phase proteins C-reactive protein (CRP) and fibrinogen were significantly increased in the ACEI group compared to the control group. CONCLUSIONS: In any case of angioedema in the head and neck region, a side effect of ACEI must be taken into consideration even if the medication has been taken for months or years.

[Argon plasma coagulation (APC) for palliative treatment of tracheostomal recurrences]. / Die palliativ-chirurgische Behandlung von Tracheostomarezidiven mit der Argon-Plasma-Koagulation (APC).

INTRODUCTION: To reduce tumor recurrences in the tracheostomal region mostly surgical measures come to the fore. PATIENTS AND METHODS: In six incurable patients with peristomal tumor recurrence, we performed nine palliative tumor reductions using argon plasma coagulation (APC). This electrosurgical non-contact technique has been described to produce effective hemostasis and favorable wound surfaces. RESULTS: In all nine procedures APC led to rapid and reliable hemostasis. Postoperative bleedings did not occur, and dry wound surfaces adjusted to the level of surrounding body contours considerably facilitated the wound aftercare. After eight of nine APC operations the immediate insertion of conventional cannulas was feasible instead of the tracheostomy tubes needed in the interim, and the patients were again able to change the cannula themselves. Two laryngectomized individuals could resume use of their voice prosthesis. CONCLUSION: APC is particularly suitable for the palliative surgical treatment of tumor recurrences in the tracheostomal region, because it helps to circumvent typical problems of conventional surgery.

Clinical trial with escalating doses of the antiepidermal growth factor receptor humanized monoclonal antibody EMD 72 000 in patients with advanced squamous cell carcinoma of the larynx and hypopharynx.

In this open uncontrolled phase I study, nine patients with stage III and IV squamous cell carcinoma of the head and neck (SCCHN) were treated with five administrations of the humanized antiepidermal growth factor receptor monoclonal antibody EMD 72000 in three consecutive ascending dose groups. Loading doses of 100 mg (group I), 200 mg (group II), and 400 mg (group III) were followed by four weekly maintenance doses of half the loading doses, i.e. 50, 100, and 200 mg, respectively. Two EMD 72000 administrations were scheduled before and three after surgery. The objectives of this trial were (a) to investigate the safety and toxicity of multiple EMD 72000 doses, (b) to determine the cumulative maximum tolerated dose of EMD 72000 at dosages between 300 mg and 1,200 mg, and (c) to determine the serum pharmacokinetics of EMD 72000. In total, 102 adverse events (AEs) were reported: five of toxicity grade 3, 18 of toxicity grade 2, 66 of toxicity grade 1, and 38 of toxicity grade 0. All AEs of toxicity grade 3 were considered to be not or remotely related to EMD 72000. The most frequent study drug-related AEs were fever and a transient elevation of liver enzymes. In all patients, the time to reach peak serum concentrations (tmax) was within 1-3 h of the start of each EMD 72000 infusion. Average peak serum concentrations (Cmax) after correction for dosage appeared to be dose-independent, whereas the half-life (t1/2) showed dose dependency. In conclusion, EMD 72000 was very well tolerated in patients with advanced stage SCCHN. The pharmacokinetic data from this trial suggest the feasibility of conducting future studies with weekly doses of 200 mg EMD 72000.