Non-allergic, mastocytosis-associated rhinitis.

BACKGROUND: Systemic mastocytosis (SM) is a clonal proliferative disorder of mast cells (MC) that causes pathological accumulation of mast cells in various tissues, which results in clinical symptoms (e.g. diarrhoea, urticaria) due to MC mediator release. Previous studies have shown that up to fifty percent of rhinitis symptoms in SM patients are non-allergic and it has been assumed that these nasal complaints in SM patients are due an increased nasal mast cell burden. Nevertheless, to date there are no data supporting this hypothesis. OBJECTIVE: The study aims to investigate if the presence of allergy-suggesting nasal complaints in non-allergic SM patients is correlated with objective measure of nasal mast cell burden. PATIENTS AND METHODS: Eleven adult patients with systemic mastocytosis underwent a comprehensive rhinologic work-up. All patients fulfilled the clinical ARIA criteria for rhinitis. The allergologic work-up included serological allergy testing, determination of tryptase levels (serum and nasal secretion), skin prick testing, and nasal provocation testing. RESULTS: Ten out of eleven SM patients with clinical persistent allergic rhinitis were found to be non-allergic. In these patients, the most predominant symptoms were rhinorrhea, sneezing, and itching. All three symptoms were strongly correlated with the nasal tryptase level but not to the level of serum tryptase. CONCLUSION AND CLINICAL RELEVANCE: Non-allergic persistent nasal complaints in systemic mastocytosis were significantly correlated with elevated nasal tryptase level as a measure of local MC burden. Furthermore, elevated nasal tryptase correlated with persistent rhinorrhea, sneezing, and itching as predominant symptoms, which seems to characterize a non-allergic mastocytosis-associated rhinitis (NAMAR) in systemic mastocytosis.

[Food allergies: significance, interfaces, and prospects in otorhinolaryngology]. / Nahrungsmittelallergien: Bedeutung, Schnittstellen und Perspektiven der HNO-Heilkunde.

Perceived and objective food hypersensitivity reactions are increasing steadily in the western countries. Therefore, otorhinolaryngologists are facing more frequently the challenge to evaluate individual food hypersensitivity reactions, to set these reactions into context with otorhinolaryngologic symptoms and to start systemic and appropriate diagnostic procedures and possibly therapy. Although a good portion of the perceived food hypersensitivity reactions can neither be objectivated nor causaly linked to the occurring symptoms, the recent literature provides documentation, suggestions and prospects for the link between food hypersensitivity reactions and distinct ENT-diseases. Based on that, this review intends to provide an overview of the current knowledge about the impact of food hypersensitivity reactions on otorhinolaryngologic diseases. The aim of the article is to give support in assessing this intricate issue in the daily otorhinolaryngological practice.

Intravital microscopy of pulmonary microcirculation after single lung transplantation in pigs.

BACKGROUND: Pulmonary reperfusion injury is a significant risk factor following lung transplantation (LTx). Unfortunately, in vivo observations and quantitative analyses of the pulmonary microcirculation following LTx are technically demanding. METHODS: Pigs, weighing 18 to 22 kg, served as the laboratory animals. The left lung was harvested and preserved using donor aortic vessel segments, the pulmonary artery, and the cuff of the lung veins were extended. After 4 hours of ischemia, the lungs were transplanted by direct connection of the conduits to the left atrial appendage and the left pulmonary artery of the recipient. The lungs were placed extrathoracically and ventilated. The recipient left lung was excluded. With this procedure, mechanical trauma to the lung and moving artefacts were avoided. Intravital microscopic observation became feasible. RESULTS: Following reperfusion, oxygenation of pulmonary venous blood was excellent. However, blood flow distribution was significantly reduced to the transplanted lung compared with the native right recipient lung. Pulmonary vascular resistance was significantly increased, dropping from 3500 to 1000 dynes x s x cm(-5) during reperfusion compared to a value of 500 for the native right lung. The pulmonary microcirculation showed a significant number of no-reflow areas with extremely reduced red blood cell velocities. Greater than 90% of microvessels (<30 microm) showed velocities below 0.1 mm/sec. In conclusion, microvascular injury seems to be a major pathogenic factor for the development reperfusion failure. Quantification of alterations within the microvasculature may shed light on various treatment modalities that reduce perfusion failure.

Influence of steroids on microvascular perfusion injury of the bowel induced by extracorporeal circulation.

BACKGROUND: Extracorporeal circulation is associated with gastrointestinal complications. By means of intravital microscopic methods, we investigated whether preoperative treatment with steroids can attenuate the impairment of the bowel microcirculation. METHODS: In 20 pigs, a partial left heart bypass (pLHB) was established. A loop of the terminal ileum was exteriorized for intravital-microscopic observation. Seven sham-operated animals served as controls. In 13 animals, pLHB was established for 2 hours with a flow rate of 2,000 mL per minute; 7 of the animals received 20 mg/kg body weight prednisolone preoperatively. The microcirculatory network was analyzed before, during pLHB, and 2 hours after bypass. RESULTS: Despite unchanged macro-hemodynamics, pLHB resulted in a significant microvascular perfusion injury of the small bowel. Arteriolar vasoconstriction and a reduction of perfused capillaries per unit area (functional capillary density) to 30% of prebypass values could be found. Blood cell velocities were reduced in submucuous collecting venules. In the steroid-treated animals, the functional capillary density remained normal. In addition, arteriolar vasoconstriction could be prevented. CONCLUSIONS: Treatment with prednisolone largely prevents the microcirculatory alterations in the small bowel induced by extracorporeal circulation.

[Decision making in non resectable head and neck tumours]. / Nicht resektable Kopf-Hals-Tumoren und deren Therapie.

Decision Making in Non Resectable Head and Neck Tumours. Advanced squamous cell carcinomas of the oral cavity, oro-, hypopharynx and larynx often have to be categorised as non resectable disease. Complex decision making for therapy is influenced by morphological, social and ethical aspects. In case of non resectability, simultaneous chemo radiation therapy is evident and recommended. Different substances for additional chemotherapy like Cis-, Carboplatine, 5-Fluorouracile, Mitomycin C and Taxans are in use. Alternatively for selected cases (to avoid total glossectomy for instance) brachytherapy is recommended. Salvage surgery after primary chemo radiation is predominantly common in residual neck disease. Sole chemotherapy is suggested for second or third line palliative treatment.

Is there a role for chemosensitivity tests in head and neck cancer?

Despite many advances in predictive testing of human malignancies, we are far from using it routinely in clinical practice. Investigating the responsiveness of solid tumors to cytostatic drugs is particularly challenging. Nevertheless, for head and neck cancer, chemosensitivity testing is an increasingly attractive option, since chemotherapy has proven to have curative potential in the therapy of head and neck cancer, in particular in combination with radiation. The significant need for predictive methods to identify patients responsive to therapy, first of all in organ preservation programs, which is an alternative to first-line surgery, had recently renewed the discussion on a possible role of chemosensitivity testing in head and neck cancer. In this review, we discuss the current state of chemosensitivity testing in head and neck cancer. Recent methodological developments, in particular elimination of photochemical artifacts and inclusion of stromal cell response studies, may soon augment the value of ex vivo chemosensitivity testing for the management of head and neck cancer.

[Diagnosis with (18)F-FDG PET scan after larynx preservation by primary radiochemotherapy]. / Diagnostik mittels (18)F-FDG-PET nach Larynxorganerhalt durch primäre Radiochemotherapie.

PATIENTS AND METHODS: In a group of 20 patients undergoing chemoradiation for larynx organ preservation after diagnosis of laryngeal and hypopharyngeal carcinoma, (18)F-fluordeoxyglucose positron emission tomography ((18)F-FDG-PET) was performed before the start of therapy. After i.v. application of 240 MBq FDG, a dynamic PET in 3-D-mode was performed over 90 min (Siemens CTI ECAT EXACT HR(+)). Analysis was done visually and semiquantitatively (60-90 min p.i.) following iterative reconstruction. Additional (18)F-FDG-PET investigations were done and correlated with the clinical outcome in 16/20 patients at 3 months and in 14/20 patients at 6 months after the end of therapy. RESULTS: In 17/20 patients (85%), the preclinical (18)F-FDG-PET correlated well with the histologically confirmed primary tumor. Three cases were false negatives. In one case this was due to an increased glucose value (203 mg%). After 3 months, 8/13 (62%) patients showed a positive correlation between clinical and PET results (sensitivity 100%, specificity 70%). After 6 months, 9/11 (82%) patients presented clinically normal PET results. PET results were false negative in one case (sensitivity 67%, specificity 88%). CONCLUSION: The data of our trial slightly reduce the enthusiasm of early (18)F-FDG-PET detection of residual disease after chemoradiation in resectable laryngeal or hypopharyngeal cancer. Further trials should optimize the calculation integrating the exact quantification of glucose metabolism with the aim of improving sensitivity and specificity.

Prognostic impact of EBV-related LMP-1, histologic type, and environmental factors in nasopharyngeal carcinoma in a German population.

INTRODUCTION: This retrospective study addressed the possible involvement of latent Epstein-Barr virus (EBV) infection, in particular LMP-1 expression, and further exogenous factors, i.e. tobacco, alcohol and occupational hazardous substances, in nasopharyngeal carcinoma (NPC) in a German population. PATIENTS AND METHODS: From 1980 to 2000, 44 patients suffering from histologically confirmed NPC were entered into the study. 33 specimens were available for immunostaining (IHC) to analyze LMP-1 expression. Information about environmental exposures were obtained employing a detailed standardized questionnaire. RESULTS: Outcome of patients with squamous cell NPC (SC-NPC) was significant worse than that of those with non-keratinizing NPC (NK-NPC). Age and tumor size correlated with response to therapy. The group with negative conventional LMP-1 staining showed better overall survival after 5 years compared to the group with positive or marginally positive LMP-1 detection (not significant). Nevertheless, after staining by tyramid-augmented IHC (TSA-IHC), nearly all specimens with negative LMP-1-staining in conventional IHC were found to be clearly positive. All patients with SC-NPC were smokers. The distribution of smokers and non-smokers in the group of NK-NPC was balanced. Comparable to the tobacco observation, there was also a correlation between high alcohol consumption and SC-NPC. CONCLUSION: Prognosis of NPC is mainly dependent on histologic type. Prognostic impact of LMP-1 is still unclear since LMP-1 was detected in all specimens using TSA-IHC. Therefore, TSA-IHC-LMP-1 detection might be interesting for diagnostic specification and development of new therapeutic strategies in NPC.

Extracorporeal circulation induced microvascular perfusion injury of the small bowel.

Gastrointestinal complications following cardiopulmonary bypass (CPB) are relatively uncommon, but are associated with a high mortality rate. Impairment of bowel perfusion during and following CPB may serve as a trigger for the development of multiorgan failure. The aim of our study was the development of a new animal model allowing quantitative analysis of small bowel microcirculation during and after CPB. Twelve Landrace pigs served as laboratory animals. A 15-cm loop of the terminal ileum was exteriorized for microscopic observation. In 6 animals, a normothermic, partial left heart bypass (pLHB) was established for 2 h with a flow rate of 2,000 ml/min. Arterioles, collecting venules and the capillaries of the small bowel were recorded for the analysis of the microcirculation. All parameters were recorded prior to, during pLHB and up to 2 h after weaning off the bypass. Six sham operated animals served as controls. Despite unchanged hemodynamics, pLHB leads to microvascular perfusion disturbances of the small bowel. In pLHB animals, blood cell velocity in postcapillary venules (30-70 microm) was significantly decreased during and following bypass. Capillary density was also reduced during bypass and decreased even further after pLHB to only 30% of the control values. With this new large animal model for quantitative assessment of microvascular perfusion of the small bowel during CPB, it could be clearly demonstrated that partial normothermic left heart bypass leads to a significant disturbance of the small bowel microcirculation even under stable hemodynamic conditions.

Dopexamine attenuates microvascular perfusion injury of the small bowel in pigs induced by extracorporeal circulation.

BACKGROUND: Cardio-thoracic surgery with the use of extracorporeal circulation may lead to an impairment of splanchnic perfusion. The aim of this study was to investigate the effect of dopexamine on gastrointestinal microvascular perfusion failure due to extracorporeal circulation. METHODS: Twenty landrace pigs served as laboratory animals. A loop of the terminal ileum was exteriorized for microscopic observation. In 13 animals a partial left-heart bypass (pLHB), with a non-pulsatile pump flow of approximately 50% of the cardiac output, was established for 2 h. Seven animals received a continuous i.v. infusion of 3 micrograms kg-1 min-1 dopexamine from the beginning of pLHB to the end of the experiment. Seven sham-operated animals served as controls. The microcirculatory network was analysed by means of intra-vital microscopy prior to, during pLHB, and 2 h after bypass. RESULTS: Despite normal haemodynamics measured by arterial pressure and cardiac output, pLHB led to significant impairment of microvascular perfusion characterized by arteriolar vasoconstriction, reduction of functional capillary density (FCD) to 30% 2 h after weaning off bypass and diminished blood-cell velocities in submucous venules. Dopexamine attenuated this perfusion impairment, preventing arteriolar vasoconstriction. FCD remained normal. CONCLUSION: Our data demonstrate that treatment with the vasoactive drug dopexamine leads to a significant reduction of the perfusion injury of the small bowel.

[Organ preservation in advanced laryngeal and hypopharyngeal carcinoma by primary radiochemotherapy. Results of a multicenter phase II study]. / Organerhalt beim fortgeschrittenen Larynx- bzw. Hypopharynxkarzinom durch primäre Radiochemotherapie. Ergebnisse einer multizentrischen Phase-II-Studie.

INTRODUCTION: Regarding the promising results of international trials we conducted the first German prospective multicentre phase II trial for organ preservation with primary simultaneous chemoradiation in advanced laryngeal and hypopharyngeal cancer. PATIENTS AND METHODS: 28 of 30 recruited patients suffering from stage II and III (UICC) laryngeal and hypopharyngeal cancer were treated with primary simultaneous chemoradiation within an organ preservation program and monitored in follow-up of one year. Exclusion criteria included tumor infiltration of the laryngeal cartilage, bilateral neck nodes (N2c) and need for flap reconstruction in case of laryngectomy. The protocol included an accelerated concomitant boost chemoradiation (66 Gy) with Carboplatinum (70 mg/m2 1st and 5th week) and a restaging procedure one month after therapy. In case of residual disease, salvage laryngectomy and/or neck dissection were performed. RESULTS: After follow-up of one year 20 of 28 patients (71%) were presented with stable complete remission and functionally preserved larynx. Of these 20 patients 3 developed pulmonary metastases, 1 secondary primary carcinoma of the lung and 3 neck metastases which needed neck dissections. The other patients showed in 4 cases relapsing tumor which was indicated for laryngectomy. One patient needed tracheotomy because of persisting edema and 2 patients died due to tumor progress. One patient died after complications due to salvage surgery. CONCLUSION: The organ preservation protocol was feasible with well tolerated early toxicity. Problems of screening for recurrent disease, salvage surgery and late toxicity should be noted and pronounced in patient information. Further studies should focus on the improvement of patient selection which could be realized by induction Chemotherapy (using new components like taxan) and/or use of prediction factors such as tumor volume and hemoglobin levels.