Burkhard Kramp

Laser Scanning Microscopy of the Human Larynx Mucosa: A Preliminary, Ex Vivo Study

Objective: Laser scanning microscopy (LSM) supplies in vivo information from epithelia up to depths between 0.1 to 0.5 mm. The aim of this ex vivo prospective pilot study was to investigate the potential use of LSM for the diagnosis of laryngeal cancer and its precursors.

Poly(3-hydroxybutyrate) (PHB) patches for covering anterior skull base defects – an animal study with minipigs

Conclusion: We conclude that PHB patch material may fulfil the specific requirements that are necessary for a dural substitute, including defect closure, stability and biocompatibility. Our results support the assumed positive influence of PHB on bone regeneration. Objectives: Although many experimental and clinical studies have been performed to identify a suitable material to repair defects of the dura mater, no ideal dural substitute is currently available. PHB is a biodegradable and biocompatible polymer that might serve as dural substitute and osteosynthesis material in cranial bone defects. Materials and methods: Different standardized PHB patches were used in six minipigs for covering defined bone defects in the anterior skull base including a dura mater lesion as well as in the frontal sinus front wall. After a defined time of implantation of 3, 6, and 9 months PHB patches were explanted and examined for clinical findings, biodegradation, presence of microorganisms, histological findings, and electron microscopy. Results: The examinations revealed an increasing closure of bone defect corresponding with time. The anterior skull base bone defect was completely closed after 9 months. The histological findings revealed a connective tissue and callus formation around the PHB patches with fibroblasts and foreign body/giant cell reaction growing through PHB membrane pores. There were no reactions or adhesions between brain and PHB or dura mater and PHB, respectively. Investigations of biodegradation and electron microscopy revealed a continuous breakdown of PHB in the course of time with variations due to different PHB structures. Microbiological investigations could not detect any florid intracranial infection.

Simultane radiochemotherapie mit carboplatin bei patienten mit inoperablen fortgeschrittenen Kopf-Hals-Tumoren der stadien UICCIII und IV

HintergrundDie Therapieergebnisse der Behandlung fortgeschrittener Tumoren der Kopf-Hals-Region mit alleiniger Bestrahlung sind unbefriedigend. Eine simultane Radiochemotherapie verbessert diese Resultate vermutlich. In einer retrospektiven Analyse wurden Ergebnisse nach simultaner Radiochemotherapie an der Universität Rostock ausgewertet.Patienten und MethodenVon 1991 bis 1996 wurden 92 Patienten mit Kopf-Hals-Tumoren der Stadien UICC III und IV nach palliativer Operation (n = 37) oder primär (n = 55) mit einer simultanen Radiochemotherapie (1,8 Gy bis 63 Gy; 70 mg Carboplatin/m2 KOF Tage 1 bis 5 und 29 bis 33) behandelt. Analysiert wurden der Remissionsstatus sechs Wochen nach Therapieende, das Gesamt- und tumorspezifische Überleben, die lokale Kontrolle sowie die Akuttoxizität.ErgebnisseSechs Wochen nach Radiochemotherapie erreichten 56,5% der Patienten eine komplette und 36% der Patienten eine partielle Remission, ein “no change” war bei 7,5% der Patienten festzustellen. Bei einer medianen Beobachtungszeit von 42 Monaten (sechs bis 74 Monate) betragen kumulative Gesamtüberlebensrate, tumorspezifische Überlebens- und lokale Kontrollrate nach fünf Jahren 24,3%, 28,9% und 18,0%. Sowohl unials auch multivariat zeigen sich die Operation vor Radiochemotherapie und univariat das UICC-Stadium III als signifikant günstige Prognosekriterien hinsichtlich aller ausgewerteten Kriterien; multivariat ergibt sich ein signifikanter Vorteil hinsichtlich des Gesamtüberlebens für das UICC-Stadium III. Ein prätherapeutischer Hämoglobinwert < 7, 0 mmol/1 (11,27 g/dl) verschlechtert uni- und multivariat signifikant die lokale Kontrolle. Die Akuttoxizität war mit 10% Grad-3- und -4-Mukositiden, 12% Grad-3-Leukopenie vertretbar, eine Thrombopenie Grad 3 sowie eine Leukopenie Grad 4 traten nur jeweils bei einem Patienten auf.SchlußfolgerungDie vorgestellte Therapieoption ist gut durchführbar. Ob eine zusätzliche Operation die Ergebnisse der simultanen Radiochemotherapie verbessern kann, muß in einer randomisierten Studie überprüft werden.AbstractBackgroundThe results of treating advanced tumors in the head and neck region with radiotherapy alone are disappointing. Concurrent radiotherapy and chemotherapy may improve this situation. The treatment results of concurrent radiochemotherapy at the University of Rostock were analyzed retrospectively.Patients and MethodsFrom 1991 to 1996 92 patients with head and neck tumors were treated With concurrent radiochemotherapy (1.8 to 63 Gy; 70 mg/m2 carboplatin day 1 to 5 and 29 to 33) with palliative tumor resection (n = 37) or without surgical treatment (n = 55). Remission rate, overall survival and disease-free survival, local control and acute toxicity were analyzed.ResultsSix weeks after radiochemotherapy 56.5% of patients had a complete remission, 36% a partial remission and 7.5% “no change”. With a median follow-up of 42 months (6 to 74 months) overall survival, disease-free survival and local control were 24.3%, 28.9%, 18.0% 5 years after treatment. All these criteria were significantly better in patients with palliative tumor resection compared to no surgical treatment (uni- and multivariate) and in patients With Stage III than in patients with Stage IV carcinomas (univariate), overall survival was significantly better in patients with Stage III (multivariate). A pretherapeutic Hb level below 7.0 mmol/1 (11.27 g/dl) reduced the local control significantly (uni- and multivariate). Grade III and IV mucositis was detected in 10%, Grade III leucopenia in 12% of treated patients. Grade IV leucopenia and Grade III thrombopenia were observed in 1 patient each.ConclusionThe toxicity of this treatment is tolerable. However, additional trials must be conducted before considering the palliative tumor resection as standard therapy.

Prospective controlled study of microbial colonization of the trachea in tracheotomized and laryngectomized patients with HME (heat and moisture exchanger)

Conclusion: The use of heat and moisture exchangers (HMEs) does not endanger tracheostomy patients in terms of additional exposure to pathogenic microorganisms. Objective: Stoma filters in the form of HMEs cause a beneficial convection of respiratory air in tracheotomized and laryngectomized patients. We investigated whether or not this may lead to an altered microbial ecology in the non-physiologically colonized lower respiratory tract. Materials and methods: To test this hypothesis, material from the trachea of stoma patients was prospectively collected utilizing a standardized swab technique and subsequent aerobic quantitative culture assays of the suspended and serially diluted material. With this approach, we examined the microbial flora in 6 and 5 patients after laryngectomy/tracheostomy, respectively, without any protection, in 11 patients after laryngectomy with a bib, and in 8 laryngectomized patients with an HME. Results: In all three groups, Staphylococcus aureus and Candida albicans were most frequently demonstrated. The microbial count of facultative pathogenic agents ranged between 3×102 colony forming units (cfu)/ml and 106 cfu/ml and was similar in the three groups. With respect to the absence of inflammatory symptoms in every patient, all isolates could be regarded as colonizers. Among the antibiotics tested with each isolate, cefuroxime proved to be the most effective against the facultative pathogenic bacteria.

Subjective voice quality, communicative ability and swallowing after definitive radio(chemo)therapy, laryngectomy plus radio(chemo)therapy, or organ conservation surgery plus radio(chemo)therapy for laryngeal and hypopharyngeal cancer

This retrospective analysis focusses on the impact of therapy on perceived long-term post-cancer treatment function. A validated questionnaire including items and components for the assessment of communicative ability, quality of voice and swallowing was sent to 129 patients. All patients were treated between 1998 and 2007. A total of 76 patients (58.9%) with carcinoma of the larynx or hypopharynx replied to the questionnaire. Data was evaluated retrospectively. Therapy delivered was definitive radio(chemo)therapy (defchRT/RT) (21/76, 28%), laryngectomy + radio(chemo)therapy (LE + chRT/RT) (28/76, 37%), or larynx conservation surgery + radio(chemo)therapy (LCS + chRT/RT) (27/76, 36%). Radiotherapy was administered using 2D- or 3D-conformal planning. The most common concomitant chemotherapy delivered was cisplatin + 5FU. For statistical analyses of the components, averages were calculated and tested using the Kruskal–Wallis test and the U-test of Mann and Whitney. Differences were assessed by the Monte Carlo method or Fishers exact test. The single item rates were compared with Fishers exact test. Mean follow-up was 56.7 months (range, 8–130 months). After defchRT/RT, patients trended towards more substantial–strong hoarseness compared with LCS + chRT/RT (P = 0.2). After LE, patients were dissatisfied with their artificial larynx/electrolarynx and the tone of their voice (P = 0.3, P = 0.07) and communicative ability (P = 0.005, P = 0.008) compared with those treated with defchRT/RT and LCS + chRT/RT, respectively. Dysphagia and additional percutaneous endoscopic gastrostomy (PEG) feeding were more frequent after defchRT/RT in comparison with the other two groups (P < 0.05). Voice quality and communicative ability were slightly worse after defchRT/RT and LE + chRT/RT, but satisfying with all treatment modalities. Further development of the therapy approach is necessary to reduce long-term side effects, with measures of post-treatment function as important endpoints.

Die mikrobiologische Oberflächenbesiedlung verschiedener Stimmprothesenarten in der Zeitkinetik

OBJECTIVE For the vocal rehabilitation of laryngectomized patients, voice prostheses are actually one of the best known methods. Caused by the surface colonisation with bacteria and fungi the life time of the prostheses is limited to 3-4 months. MATERIAL AND METHODS In a time period of 127 months we analysed the surface colonisation of 118 voice prostheses. RESULTS The mean life time of the prostheses was 156 days. In reference to the prosthesis model we also recorded different times of usage (ESKA-Herrmann 141, Provox 2 184 and Provox 1 204 days (p>0.05)). In the microbiological examination the dominating bacteria were S. aureus, Klebsiella sp. and Proteus sp. It was possible to cultivate all these bacteria on every type of prosthesis used in the study. In addition C. albicans, C. glabrata, C. krusei and C. tropicalis were the main fungi on the silicone surface. Thereby a more frequent colonisation with C. krusei on ESKA-Herrmann prostheses was measured, caused by the bigger contact area with saliva on this model (p=0.034). CONCLUSIONS Because of the similar position and way of function, all types of voice prostheses are colonized by almost the same species of bacteria and fungi. But in dependency of the type an affinity of individual species to special prostheses exist. The knowledge of these individual affinities is necessary for the further development of voice prostheses. Furthermore the diversity of bacteria and fungi species showed a level of saturation on the surface. This is caused by the limited space on the silicone prostheses.

Tracheostomy cannulas and voice prosthesis

Cannulas and voice prostheses are mechanical aids for patients who had to undergo tracheotomy or laryngectomy for different reasons. For better understanding of the function of those artificial devices, first the indications and particularities of the previous surgical intervention are described in the context of this review. Despite the established procedure of percutaneous dilatation tracheotomy e.g. in intensive care units, the application of epithelised tracheostomas has its own position, especially when airway obstruction is persistent (e.g. caused by traumata, inflammations, or tumors) and a longer artificial ventilation or special care of the patient are required. In order to keep the airways open after tracheotomy, tracheostomy cannulas of different materials with different functions are available. For each patient the most appropriate type of cannula must be found. Voice prostheses are meanwhile the device of choice for rapid and efficient voice rehabilitation after laryngectomy. Individual sizes and materials allow adaptation of the voice prostheses to the individual anatomical situation of the patients. The combined application of voice prostheses with HME (Head and Moisture Exchanger) allows a good vocal as well as pulmonary rehabilitation. Precondition for efficient voice prosthesis is the observation of certain surgical principles during laryngectomy. The duration of the prosthesis mainly depends on material properties and biofilms, mostly consisting of funguses and bacteries. The quality of voice with valve prosthesis is clearly superior to esophagus prosthesis or electro-laryngeal voice. Whenever possible, tracheostoma valves for free-hand speech should be applied. Physicians taking care of patients with speech prostheses after laryngectomy should know exactly what to do in case the device fails or gets lost.

Distribution of circulating natural killer cells and T lymphocytes in head and neck squamous cell carcinoma.

OBJECTIVE Natural killer (NK) cells are capable of eliminating malignantly transformed cells without prior sensitization. In contrast to NK-cells, T lymphocytes possess antitumourous activity that is restricted to major histocompatibility complex (MHC) recognition. The aim of this study was to determine the causes of the different distributions of these cell types in the peripheral blood of patients with head and neck squamous cell carcinomas (HNSCC). METHODS A cohort of 105 subjects was divided into three clinical groups: non-treated HNSCC patients, treated relapse-free HNSCC patients and healthy control subjects. Peripheral blood mononuclear cells (PBMC) were isolated from venous blood, subsets were depleted, flow cytometric counts were made and subsequently correlation analyses with clinical parameters were performed. RESULTS Treated relapse-free HNSCC patients have a significantly increased mean proportion of NK-cells in PBMC of 26.39% (p<0.001), whereas T lymphocytes and natural killer-T-(NKT) cells of treated patients have a significantly decreased mean proportion in PBMC of 55.15% (p<0.05) at least 12 months after treatment. This inverse redistribution of these two subsets is reflected in a significantly increased mean NK/T-ratio of 0.54 (p<0.05) in treated patients. The NK/T-ratio correlates with the systemic invasiveness of the type of therapy patients undergo and is highest after surgery with adjuvant radiochemotherapy (0.64, rs=0.334, p<0.01). This appears to be a post-therapeutic long-term effect in treated patients, as they had a mean relapse-free period until venous puncture of 47.9 months in our study. We also demonstrated age-dependent changes in the peripheral distribution of T- and NK-cells. CONCLUSION These findings reveal new aspects in understanding tumour biology and interactions with the cellular immune system which provide novel starting points for further research.