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Biomedical subjects

B Wollenberg

Publications and source records attributed to B Wollenberg.

At least 19 recordsLinked to original sources

[Surgery of the parapharyngeal adenomas].

Pleomorphic adenomas are the most common tumors of the parapharyngeal space (PPS) and often grow to an enormous size before becoming visible or symptomatic. CT and MRI scans are important in both diagnosis and surgical treatment. There are basically four different surgical approaches (transoral-transpalatal, transcervical-submandibular, transparotid und transmandibular) to the anterior PPS. Wide and direct exposure of the PPS is provided by a midline mandibulotomy with transection of the floor of the mouth. Owing to its morbidity this approach is reserved exclusively for extended tumors. The transcervical-submandibular route with blunt finger dissection generally offers adequate access for total tumor removal. For adenomas arising from the parotid gland a transparotid approach may be utilized. Adenomas located medially are better be resected transorally by splitting the soft palate.

Adenoma↗

[Chronic pain therapy for patients with head and neck tumors].

Patients with tumors of the head and neck region commonly suffer from chronic pain, which is often treated insufficiently. Pain management according to the WHO analgesic ladder can effectively reduce pain in most patients. For head and neck cancer, specific aspects of tumor localization and psychosocial factors must be taken into consideration.

Analgesics↗

High energy probe for detecting lymph node metastases with 18F-FDG in patients with head and neck cancer.

AIM: of this study was to validate a newly developed high energy probe (positron emission probe, PEP) optimised for localising PET tracers in vivo. PATIENTS AND METHODS: Physical investigations included determination of full width at half maximum (FWHM) values at a distance of 1 cm and angular resolution using different point sources. Values obtained with the new probe were compared to those of a conventional gamma probe (CGP). Additionally, PET studies were performed in 36 patients (6 women, 30 men) with proven head and neck cancer and suspected lymph node metastases (Axis, Marconi/Philips) after administering 250-320 MBq (18)F-FDG. Subsequent to PET investigations (18)F-FDG uptake in cervical regions was measured using the PEP. PEP investigations were carried out bilaterally in 5 lymph node (LN) levels (Robbins' classification of the neck). Results of probe studies were correlated with visual and semiquantitative PET evaluations, US and histological findings. RESULTS: FWHM of the new probe was 7 mm (CGP 22 mm) at 662 keV ((137)Cs) and angular resolution resulted in 8 degrees (CGP 60 degrees ). In 29 out of 36 patients LN metastases were suspected due to ultrasound investigations. After neck dissection, histology confirmed LN metastases in 21 patients. Sensitivity (sens.) of US amounted to 95% and specificity to 40%. In 18/21 patients LN metastases were detected by PET (sens. 86%). PET scans failed to diagnose the LN status correctly in 6/36 patients (accuracy 83%). Employing the PEP probe in 20/21 patients LN metastases were identified (sens. 95%), and LN status was determined accurately in 29/36 patients (accuracy 81%). Tumour/background ratios of PEP measurement and results of semiquantitative PET analyses were comparable. CONCLUSIONS: PEP measurement is a promising method for preoperative planning of the extent of neck dissection in patients with head and neck cancer and further for radioguided localising PET tracer accumulation during surgery.

Adult↗

[Salivary gland carcinomas. 1. Epidemiology, etiology, malignancy criteria, prognostic parameters and classification].

Salivary gland carcinomas comprise a rare group of malignant tumors which are difficult to diagnose and treat due to their histopathologic diversity, variable clinical course and anatomic location, particularly with respect to the facial nerve. The present paper summarizes important features of these tumors, including recent advances in their management, i.e., diagnosis, surgery of the primary tumor, neck dissection, radiation therapy, and updates risk factors, criteria of malignancy, and prognostic variables, taking into account the relevant literature. Additionally, the present paper highlights briefly the survival rates of patients suffering from salivary gland carcinomas. The present overview is divided into two parts: the first is focused on epidemiology, etiology, criteria of malignancy, prognostic factors, and tumor classification, while part II discusses the diagnosis and therapy of salivary gland carcinomas.

Carcinoma↗

[Salivary gland carcinomas Part II. Diagnosis and therapy].

Salivary gland carcinomas comprise a rare group of malignant tumors which are difficult to diagnose and treat due to their histopathologic diversity, variable clinical course and anatomic location, particularly with respect to the facial nerve. The present paper summarizes important features of these tumors, including recent advances in their management, i.e., diagnosis, surgery of the primary tumor, neck dissection, radiation therapy, and updates risk factors, criteria of malignancy, and prognostic variables, taking into account the relevant literature. Additionally, the present paper highlights briefly the survival rates of patients suffering from salivary gland carcinomas. The present overview is divided into two parts: the first is focused on epidemiology, etiology, criteria of malignancy, prognostic factors, and tumor classification, while part II discusses the diagnosis and therapy of salivary gland carcinomas.

Humans↗

High-resolution ultrasonography in gastrointestinal graft-versus-host disease.

Gastrointestinal graft-versus-host disease (GVHD) is one of the main causes of therapy-related death after allogeneic hemopoietic stem cell transplantation. Early diagnosis and immediate treatment are probably essential for improving clinical outcome. High-resolution sonography allows the evaluation of single bowel wall layers throughout the small and large bowel. We report the sonographic findings of seven consecutive patients with histologically confirmed GVHD grade II-IV of the gastrointestinal tract. The patients were examined sonographically within the 1st week after onset of clinical symptoms. Dilatation of the colon and striking bowel wall thickening were early and common features in these patients. Sonography may become a useful tool for diagnosis of patients with gastrointestinal GVHD. Its role for preclinical diagnosis, grading of severity of disease, and guiding therapy of patients with gastrointestinal GVHD warrants evaluation in prospective studies.

Adult↗

Profile identification of disease-associated humoral antigens using AMIDA, a novel proteomics-based technology.

We describe AMIDA (autoantibody-mediated identification of antigens), a novel target identification technology based on the immunoprecipitation of disease-specific antigens by autologous serum antibodies followed by two-dimensional electrophoretic separation, and their identification via mass spectrometry. Twenty-seven potential carcinoma antigens were identified including proteins of hitherto unknown function. Validation of one of the identified antigens, cytokeratin 8, revealed its de novo expression in hyperplastic tissue, gradual overexpression with increasing malignancy, and ectopic localization on the cell surface. Furthermore, a strong prevalence of CK8-specific antibodies occurred in the serum of cancer patients already at early disease stages. In situ hybridization for one marker of unknown function, KIAA1273/TOB3, demonstrated its strong overexpression in head and neck carcinomas, thus making it a likely tumor antigen candidate. Eventually, AMIDA could foster significant improvements for the diagnosis and therapy of human diseases eliciting a humoral immune response, and allows for the rapid identification of new target molecules.

Allergy and Immunology↗

Clinical relevance of circulating tumour cells in the bone marrow of patients with SCCHN.

BACKGROUND: Clinical outcome of patients with head and neck squamous cell carcinoma (SCCHN) depends on several risk factors like the presence of locoregional lymph node or distant metastases, stage, localisation and histologic differentiation of the tumour. Circulating tumour cells in the bone marrow indicate a poor prognosis for patients with various kinds of malignoma. The present study examines the clinical relevance of occult tumour cells in patients suffering from SCCHN. PATIENTS AND METHODS: Bone marrow aspirates of 176 patients suffering from SCCHN were obtained prior to surgery and stained for the presence of disseminated tumour cells. Antibodies for cytokeratin 19 were used for immunohistochemical detection with APAAP on cytospin slides. Within a clinical follow-up protocol over a period of 60 months, the prognostic relevance of several clinicopathological parameters and occult tumour cells was evaluated. RESULTS: Single CK19-expressing tumour cells could be detected in the bone marrow of 30.7% of the patients. There is a significant correlation between occult tumour cells in the bone marrow and relapse. Uni- and multivariate analysis of all clinical data showed the metastases in the locoregional lymph system and detection of disseminated tumour cells in the bone marrow to be statistically highly significant for clinical prognosis. CONCLUSION: The detection of minimal residual disease underlines the understanding of SCCHN as a systemic disease. Further examination of such cells will lead to a better understanding of the tumour biology, as well as to improvement of diagnostic and therapeutic strategies.

Biomarkers, Tumor↗

[Clinical and epidemiological data of patients with malignomas of the head and neck].

BACKGROUND: The present study describes clinical and epidemiological data of patients with malignomas of the head and neck documented in the Munich Cancer Register. PATIENTS AND METHODS: Data of head and neck cancer patients treated at four departments of head and neck surgery and one of oral-maxillo-facial surgery in the area of Munich from 1978 up to now are reported. RESULTS: Incidence and mortality as a function of age, sex, and tumor localization are described in comparison to clinical and epidemiological data as specified in tumor registers of the Saarland and the USA. Moreover, TNM stages, survival, recurrence, and metastasis rates are presented. CONCLUSION: Based on the documentation of the Munich Cancer Register our study is the first to present a detailed description of clinical and epidemiological data of patients suffering from head and neck malignomas.

Adult↗

[The expression of zeta-chain of the T cell receptor as prognostic marker for patients with head and neck cancer].

INTRODUCTION: The zeta-chain as an important component of the T cell receptor (TCR) is involved in the transduction of intracellular signals and is therefore critical for T cell activation and subsequent induction of an anti-tumor response. In patients with squamous cell carcinoma of the head and neck (SCCHN) several mechanisms of immune suppression have been described. The expression of the TCR zeta-chain of both peripheral blood lymphocytes (PBLs) and tumor infiltrating lymphocytes (TILs) has been analysed in patients with SCCHN and correlated to clinical data. METHODS: TIL and PBL from 47 patients with SCCHN were obtained. To determine expression of the zeta-chain in both PBLs and TILs, double immunostaining with mAbs and flow cytometric analysis was performed. The technique combined an intracellular staining with a surface staining. RESULTS: As compared to healthy controls (n = 23), zeta-chain expression was significantly reduced (p < 0.002) in patients with SCCHN (n = 23) with lowest expression in those with UICC VI disease. Our results show a tight correlation between the loss of zeta-chain expression and the clinical aggressiveness of the tumor. Higher tumor stages frequently show a higher loss of the zeta-chain. In 11 patients zeta-chain expression of the PBL could be compared with TIL. Independent of the tumor stage the loss of the zeta-chain expression is much higher in TIL than in PBL. The loss of the zeta-chain expression also correlates with the progression of the disease. Patients with a high loss of the zeta-chain expression develop a recurrence more frequently. CONCLUSION: The loss of the zeta-chain documents a systemic immune defect, which even occurs in early tumor stages. Additionally to locoregional approaches future therapeutic strategies should also focus on systemic immunomodulation.

Biomarkers, Tumor↗

[Identification of CD11c+ myeloid dentritic cells in adenoids and in nasal mucosa of patients with and without allergies].

BACKGROUND: Dendritic cells form a link between innate and acquired immunity. They are capable to detect pathogens based on the recognition of pathogen-associated microbial molecules and trigger the appropriate type of immune responses. In humans, three major subsets of dendritic cells can be distinguished, Langerhans cells of the skin, myeloid DC (MDC) and plasmacytoid DC (PDC). It was reported that PDC infiltrate nasal mucosa in allergen-induced rhinitis. Information about the role of MDC in nasal mucosa and the corresponding mucosa-associated lymphoid tissue, the nasopharyngeal adenoids, is limited. PATIENTS AND METHODS: : Here we examined the presence of MDC in adenoids and in nasal mucosa of healthy individuals (n = 9) and in patients with allergic rhinitis. MDC were detected by flow cytometry by positive staining for MHC II and CD11c and the lack of lineage markers. Dead cells were excluded from analysis. RESULTS: In adenoids, 0.4 % of all cells were MDC. Considerable numbers of MDC could also be detected in nasal mucosa. No difference was found between healthy individuals and patients with allergies (0.3 % vs. 0.45 % MDC; p = 0.12). Interestingly, MDC were absent in patients who received treatment with glucocorticoids, while very high numbers of MDC were found in patients who recently had upper respiratory tract infections. CONCLUSION: Our results demonstrate for the first time the presence of MDC in nasal mucosa. MDC numbers were similar in healthy individuals and in patients with allergy. This study forms the basis for examining the role of MDC in the pathogenesis of allergic rhinitis, and for the modulation of MDC functional activity with microbial molecules such as CpG oligonucleotides.

Adenoids↗

Tumor necrosis factor alpha negatively regulates the expression of the carcinoma-associated antigen epithelial cell adhesion molecule.

BACKGROUND: The epithelial cell adhesion molecule (EpCAM) is a homophilic and Ca2+ independent adhesion molecule that is expressed de novo in squamous cell carcinoma (SCC) but is absent in the majority of healthy squamous epithelia. EpCAM expression correlates with cell proliferation and dedifferentiation along with a progression in tumorigenicity. To date, nothing is known about the molecular mechanisms responsible for the regulation of the EpCAM gene. METHODS: The authors analyzed the regulation of a fragment of the EpCAM promoter. RESULTS: The analyzed fragment has significant activity in EpCAM positive cells, and it is regulated negatively by tumor necrosis factor alpha (TNFalpha). This negative regulation results in diminished mRNA expression and in the down-regulation of EpCAM protein at the cell surface in SCC cells. Both effects can be mimicked by the treatment of cells with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA). TNFalpha-induced inhibition of the EpCAM expression is mediated by TNF receptor 1 through the TNF receptor-associated death domain protein (TRADD) and by the activation of nuclear factor kappaB (NF-kappaB), and it can be blocked by dominant-negative variants of TRADD and the NF-kappaB inhibitor, IkappaB. The authors provide further evidence that NF-kappaB represses EpCAM expression by competing for the transcriptional coactivator p300/CREB binding protein (p300/CBP). CONCLUSIONS: The current results provide the first insights into the regulation of EpCAM expression, which is regulated negatively by TNFalpha and TPA through the activation of NF-kappaB. The repression may rely on the competition of NF-kappaB for p300/CBP histone acetyl transferase activity, because the overexpression of p300 reverts TNFalpha effects.

Antigens, Neoplasm↗

Partially reversed intrasplenic venous blood flow detected by color Doppler sonography in two patients with hematologic diseases and splenomegaly.

We report on 2 patients with hematologic diseases (1 follicular lymphoma and 1 myeloproliferative syndrome) and splenomegaly who had partial intrasplenic portosystemic shunting demonstrated by color Doppler sonography. Intrasplenic venous blood flow was in the normal direction at the hilum of the spleen but in a reversed direction at the periphery of the spleen. This type of reversed intrasplenic flow pattern results in portosystemic shunting and might be detected more frequently when careful color Doppler mapping of the entire splenic parenchyma is performed in patients with portal hypertension. The clinical significance of this phenomenon, however, is still unclear.

Female↗

[IL-2 gene therapy in ENT carcinomas].

Suppressed cellular immunity is common in patients with squamous cell carcinoma of the head and neck (HNSCC). It was demonstrated in previous studies that administration of interleukin 2 (IL-2) results in enhanced antitumoral immunity in vitro as well as in vivo. Since the serum half-life of IL-2 is relatively short, repeated applications are necessary to achieve therapeutically effective serum concentrations, but this strategy might cause severe side effects. Therefore, methods that provide high local cytokine levels over a prolonged period of time without the need for repeated injections are desirable. Gene therapy as an innovative treatment approach using tumor cells stably transduced to produce IL-2 might meet these criteria. In vitro manipulated tumor cells, if readministered in the vicinity of non-manipulated tumor cells, may enhance a specific anti-tumor response in vivo without systemic side effects. The present manuscript reviews the current literature dealing with IL-2-protein and -gene therapy with special emphasis on head and neck cancer. Our own in vitro results with IL-2 gene therapy in conjunction with published data from other authors argue in favour of an in vivo approach for this therapeutic strategy that is currently in progress in our department.

Animals↗

[Dyspnea caused by leiomyomatous tumor of the oropharynx].

BACKGROUND: Leiomyoma and Leiomyosarkoma are not often found in ENT-diseases. PATIENTS: We report on a 62-year old female patient presenting with a 3 x 4 cm tumor in the oropharynx that had developed within a period of about three weeks. The patient complained of increasing dysphagia and dyspnea especially when lying on the left side. To secure breathing the patient had to be primarily ventilated by placing a needle percutaneously through the conical ligament and was then intubated. For this procedure the patient was positioned on the right side. The tumor measuring 3 cm, was removed surgically. RESULTS: The tumor turned out to be a leiomyomatous neoplasia of undetermined malignant potential. Since an unfavourable behaviour of such neoplasms cannot be excluded, patients with tumors of this type should be followed closely. CONCLUSIONS: In this case the tumor leads to an acute dyspnoea and a special procedure of anesthesia was necessary. Therapeutic considerations and differential diagnosis of this very rare tumor of the oropharynx are discussed by reviewing the literature.

Deglutition Disorders↗

[Functional hyposplenia after allogenic bone marrow transplantation: a case report].

Functional hyposplenia/asplenia is a severe longterm complication after allogeneic stemcell transplantation predominantly seen in patients who suffer from extensive chronic graft versus host disease (cGvHD). The risk of acquiring an overwhelming infection with encapsulated bacteria is ca. four fold increased in patients with functional hyposplenia/asplenia. Therefore follow up of patients who have received allogeneic blood stem cells (bone marrow or peripheral blood stem cells) should embrace screening for functional hyposplenia. When functional hyposplenia is diagnosed triple vaccination against streptococcus pneumonia, Haemophilus influenza type B and Meningococcus neisseria should be considered. Goldstandard in diagnosing functional hyposplenia is hepatosplenic scintigraphy. We present the case of 37 year old female in whom sonography was indicative of functional hyposplenia. The diagnosis was confirmed by scintigraphy. Sonography including color coded duplex sonography is a safe and cost saving procedure. Sensitivity, Specificity and predictive value of the following sonographic finding: a) decreasing splenic size and b) diminished or absent parenchymal blood flow are currently evaluated in a prospective study.

Adult↗