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Biomedical subjects

F Hoppe

Publications and source records attributed to F Hoppe.

At least 19 recordsLinked to original sources

Approaches to preserve larynx function in locally advanced laryngeal and hypopharyngeal cancer.

Randomized controlled studies have shown that preservation of the larynx function in patients with advanced resectable laryngeal and hypopharyngeal cancer is possible without compromising survival compared to total laryngectomy (TL). Options for preserving the larynx include function-sparing surgery, radiotherapy alone, induction chemotherapy followed by radiotherapy of responders, and concomitant radiochemotherapy. The current data suggest that induction chemotherapy followed by radiotherapy of responders is an acceptable alternative to TL for patients desiring larynx preservation. Concomitant radiochemotherapy (platinum/5-FU) leads to superior local control and larynx preservation rates compared to induction chemotherapy followed by radiation. The optimal treatment sequence for newer cytotoxic agents is, however, unclear. Such cytotoxic agents and more effective fractionation regimens as well as more advanced surgical techniques are currently evaluated. Predictive tests to successfully stratify patients for the optimal treatment option and more effective systemic therapy are needed to improve therapeutic possibilities and survival.

Antineoplastic Combined Chemotherapy Protocols↗

[Prognostic value of pretreatment CT regarding local control in oropharyngeal cancer after primary surgical resection].

PURPOSE: To evaluate the prognostic implication of tumor infiltration and volume in primarily operated oropharyngeal carcinomas. MATERIAL AND METHODS: In 80 patients with oropharyngeal squamous cell carcinomas (pT 1 = 22, pT 2 = 30, pT 3 = 19 and pT 4 = 9), the tumor volume was measured by pretreatment CT and the extent of tumor infiltration determined by postoperative histologic examination. All patients were followed clinically for local tumor recurrence for at least two years after therapy. The statistical analysis consisted of chi 2 and U tests. RESULTS: The local control rate was 79 % (63/80). Of all evaluated anatomic structures, only midline crossing correlated significantly with local recurrence (p = 0.06). No correlation of tumor volume (p = 0.19) or T stage (p = 0.60) with the local recurrence rate was found. CONCLUSION: After primary surgery, oropharyngeal carcinomas with midline crossing have an increased risk of local recurrence, whereas the tumor volume only has a minor impact on the recurrence rate. This is in contrast to laryngeal or hypopharyngeal carcinomas.

Adult↗

[Diagnostic impact of multiplanar reformations in multi-slice CT of laryngeal and hypopharyngeal carcinomas].

PURPOSE: Assessment of the diagnostic value of multiplanar reformations (MPR) in multi-slice computed tomography (MSCT) by comparing relevant anatomic structures of the larynx and hypopharynx. MATERIALS AND METHODS: MSCT of the neck was performed in 69 consecutive patients (including 30 laryngeal and 12 hypopharyngeal carcinomas). From a 4 x 1.0 mm collimation data set, 3.0-mm and 1.25-mm axial slices as well as 3-mm coronal and sagittal slices were reconstructed. Using the histological examination as gold standard, sensitivity and specificity regarding tumor infiltration for all relevant anatomical structures of the larynx and the hypopharynx were determined for each reconstruction and compared with the McNemar test. Moreover, 42 patients with laryngeal and/or hypopharyngeal carcinoma were subjectively evaluated to determine whether the respective reconstructions enables a better topographical visualization of the tumor in relation to surrounding structures and, furthermore, whether this has an influence on the therapeutical strategy (operation versus radiation therapy, type of operation, surgical approach). RESULTS: Sensitivities and specificities were not significantly different between the reconstructions. However, coronal and sagittal MPR provided a better topographical visualization of the tumor in 14 of 42 (33 %) of the patients, and influenced the therapeutical strategy in 8 of 42 (19 %) of the patients. A lowered signal-to-noise ratio impeded the evaluation of the relatively thin 1.25-mm axial slices in more than 23 % of the cases. CONCLUSION: Besides the 3-mm axial slices, coronal and sagittal MPR can improve the topographical visualization of laryngopharyngeal tumors and are recommended for preoperative MSCT of laryngeal and/or hypopharyngeal carcinomas. Additionally reconstructed 1.25-mm axial slices can be discarded since they do not hold a higher value compared to 3-mm axial reconstructions.

Adult↗

[Identification and surgical anatomy of the external branch of the superior laryngeal nerve].

Injury to the external branch of the superior laryngeal nerve (EBSLN) during thyroid surgery can cause serious consequences for patients who depend on control of pitch and a clear and forceful voice, like singers or professional speakers. We used the Neurosign 100(R) nerve monitor to identify 157 nerves in 108 patients undergoing thyroid surgery. The EBSLN was successfully identified in 98.7 % of cases. The recording electrode could be placed either into the cricothyroid muscle or the vocal cord. The latter position proved superior if the recurrent laryngeal nerve had to be identified as well. 16 percent of the nerves crossed the branches of the superior thyroid artery at or below the upper pole of the gland, posing a "high risk" for intraoperative lesions. Our data confirm the results of smaller studies reporting this type of nerve course in 12 % to 14 % of patients. The present findings show a significant number of EBSLN to be in danger of injury when the superior thyroid artery is ligated during thyroid surgery. Neuromonitoring proofed to be a reliable method to identify the nerve, which is an important element in concepts to prevent its injury.

Electromyography↗

Up-regulation of matrix metalloprotease-9 in middle ear cholesteatoma--correlations with growth factor expression in vivo?

The role of matrix metalloproteases and their regulation in the pathology of middle ear cholesteatoma is still unclear. Recently we have demonstrated that incubation of keratinocytes with cholesteatoma debris and granulation tissue extracts causes induction of gelatinase B (matrix metalloproteinase-9, MMP-9) secretion in vitro. Antibodies against a variety of growth factors revealed some inhibitory effect on MMP-9 induction, caused by debris or granulation tissue extracts. In order to investigate the coherence of growth factor expression and matrix metalloproteinase activity in vivo in middle ear cholesteatoma, we performed quantitative gelatin zymographic analysis with tissue homogenates of 37 cholesteatoma and nine external ear canal skin (EACS) samples. Furthermore we quantified levels of the cytokines IL-1alpha, IL-1beta, TNF-alpha, TGF-beta and EGF present in tissue extracts, using enzyme-linked immunosorbent assays (ELISA), and correlated cytokine concentrations with gelatinolytic activities. Zymographic analysis revealed a highly heterogeneous expression of gelatinase A and B in cholesteatoma specimens. As shown previously, MMP-9, but not MMP-2, was increased in cholesteatoma when compared to EACS samples. ELISA studies revealed a significantly elevated IL-1alpha level in cholesteatoma. Regression analysis involving gelatinolytic activity and cytokine concentrations in tissue homogenates showed no statistically significant correlation between expression of gelatinases and the cytokines IL1-alpha, IL1-beta, TNF-alpha, TGF-beta or EGF. The discrepancy between in vitro observations and the situation in vivo is discussed critically.

Cholesteatoma, Middle Ear↗

[Carcinoma of the external ear canal and middle ear as interdisciplinary challenge for ear surgery and radiotherapy].

BACKGROUND: Carcinoma of the external auditory canal are tumours considered to have a poor prognosis. Improvement of the survival rate by surgical means alone is not possible. Individual therapy modalities as a result of an interdisciplinary approach between otosurgeon and radiotherapist are necessary. PATIENTS AND METHODS: A series of 30 patients (3 patients pretreated at other institutions) with carcinoma of the external auditory canal and middle ear treated between 1978 and 1997 in our institutions was analysed with particular reference to tumour size and its relation to surrounding tissues, patterns of neck node involvement, surgical procedures, and radiation techniques. Clinical endpoints were freedom from local failure, overall survival, disease-free survival. The mean follow-up was 4.7 years (range: 0.1 to 18.8 years), median 3 years. RESULTS: Treatment by surgery and radiotherapy resulted in an overall 5-year survival rate of 51%. According to Pittsburgh classification the 5-year survival rate for early disease (T1- and T2-tumours) was 89%, for stage III 67% and for stage IV 39%. Most important prognostic factors were dural infiltration (all patients with dural invasion died within 2.2 years) and the infiltration of surgical margins (the 5-year survival rate of patients with complete tumour resection was 100%, but 54% in patients with tumour beyond surgical margins). 192-iridium HDR afterloading brachytherapy based on 3D CT-treatment planning is an effective tool in the management of local recurrences following surgery and a full course of external beam radiotherapy. CONCLUSIONS: Surgical resection followed by radiotherapy adapted to the stage of disease and grade of resection is the preferred treatment of cancer of the external auditory canal and middle ear.

Adult↗

[Diagnosis, treatment and results of malignant skull base tumours].

BACKGROUND: Malignant tumours of the cranial base are rare and present usually in advanced tumour stage due to the lack of early clinical symptoms. PATIENTS AND METHODS: Sixty patients with malignant tumours infiltrating the skull base were treated at the Department of Otorhinolaryngology Head and Neck Surgery, University of Würzburg between 1987 and 1999. Most of the tumours (n = 51) originated from the nose or paranasal sinuses, the epipharynx, the outer ear canal or the middle ear. Seven tumours were malignant brain tumours infiltrating the bony structures of the skull base or originated from the cranial base itself. Two patients suffered from metastases of an adenocarcinoma of the prostata. The histological diagnosis was confirmed in 53 patients preoperatively and in seven patients during tumour resection. Squamous cell carcinoma (n = 24), adenocarcinoma (n = 10) and sarcoma (n = 7) were the most common histologies found. RESULTS: A radical en bloc resection of the tumour was only possible in 26 out of 60 cases. A surgical tumour reduction with postoperative radiation therapy was performed in seven patients as a palliative approach. Eight patients underwent a combined radio- and chemotherapy according to the histological diagnosis. Primary radiotherapy was the treatment of choice in eleven patients, where the tumours were located in the central area of the cranial base. Palliative radiotherapy or solely medical pain control were applied to eight patients who presented either with distant metastases or an advanced tumour growth. The mean postoperative survival following radical surgery was 48 months and after primary radiotherapy 27 months. DISCUSSION: A statistical analysis of the results is not applicable due to the great variety of the disease concerning the histological diagnosis, the tumour size and the location as well as the small number of patients.

Adenocarcinoma↗

The influence of the radicality of resection and dose of postoperative radiation therapy on local control and survival in carcinomas of the upper aerodigestive tract.

PURPOSE: To evaluate dose concepts in postoperative irradiation of carcinomas of the upper aerodigestive tract according to the radicality of resection. PATIENTS AND METHODS: In a retrospective analysis, the charts of 257 patients with histologically-proven carcinoma of the upper aerodigestive tract (40 T1, 80 T2, 53 T3, 84 T4 tumors, with nodal involvement in 181 cases) were reviewed according to the radicality of resection and dose of irradiation administered. Sixty-four patients had tumor-free resection margins (> 3 mm), 66 patients had close resection margins (< 3 mm), and 101 patients had R1 resections, and 26 patients had R2 resections. A median dose of 56 Gy was applied to the primary tumor bed and the cervical lymphatics (2 Gy/fraction, 5 fractions/week). In cases of R1 or R2 resection, or of close margins (< 3 mm), the tumor bed or, respectively, tumor residuals were boosted with doses up to a median of 66 Gy. Locoregional tumor control and survival was investigated by uni- and multivariate analyses according to T-, N-stage, grade of resection, total dose of radiation, and presence or absence of extracapsular tumor spread and lymphangiosis carcinomatosa. RESULTS: An overall 3- and 5-year survival rate of 60% and 45%, respectively, was achieved. Rates for freedom from locoregional recurrence were 77% and 72% at 3 and 5 years, respectively. The survival rates according to the grade of resection at 5 years were 67% for patients resected with tumor-free margins, 59% for patients resected with close margins, 26% for patients with R1 resection, and 27% for patients with R2 resection. Within a median follow-up period of 4.7 years for living patients, a total of 67 recurrences (26%) were observed (in 9% of patients resected with tumor-free margins, in 27% with close margins, in 37% of R1 resected, and in 19% of R2 resected patients). Freedom from locoregional recurrence at 3 years was achieved in 100% of the patients resected with tumor-free margins, in 92% of patients resected with close surgical margins, in 87% of R1 and 69% of R2 resected patients. In multivariate Cox-regression analysis, the variables grade of resection (p = 0.00031) and total dose of irradiation (p = 0.0046) were found as factors influencing locoregional control. Variables influencing survival according to multivariate analysis are T-stage (p = 0.0057), N-stage (p = 0.024), grade of resection (p = 0.000015), total dose of irradiation (p < 0. 000000). Extracapsular tumor spread and lymphangiosis carcinomatosa are factors of borderline significance (p = 0.055, p = 0.066). CONCLUSION: In postoperative radiotherapy of head and neck carcinomas, doses adapted to the risk of locoregional recurrent disease should be applied. Patients with R1 and R2 resections should be treated with doses of more than 68 Gy (2 Gy/fraction, 5 fractions/week) (with close margins [< 3 mm] more than 66 Gy) to achieve an improvement in locoregional control and survival.

Adult↗

Urokinase receptor up-regulation in head and neck squamous cell carcinoma.

BACKGROUND: Urokinase-type plasminogen activator is important for matrix degradation and motility of cancer cells. For effective invasion, urokinase has to be associated with its cell surface receptor.(1) METHODS: We analyzed 33 head and neck squamous cell carcinomas (hnSCC) and 14 mucosal tissue samples for the expression of urokinase receptor using Northern hybridization and correlated expression levels to clinical and histopathologic data. Urokinase expression was determined by fibrin zymography. RESULTS: The expression of urokinase receptor is significantly increased in hnSCC compared with adjacent mucosa. Expression levels in primary tumors show no statistically significant correlations to T staging, metastasis, recurrence, or differentiation stage of the resected tumors. Furthermore, there was no correlation between urokinase and urokinase receptor expression levels in SCC samples. CONCLUSIONS: Urokinase receptor expression is increased in hnSCC, but it is not useful as a prognostic marker for the metastatic behavior of primary tumors. Comparison of our data with previously published reports is discussed.

Adult↗

Induction of matrix metalloproteinases in keratinocytes by cholesteatoma debris and granulation tissue extracts.

Although it is generally accepted that destruction and remodeling of temporal bone associated with middle ear cholesteatoma is mainly caused by the action of osteoclasts, it has been shown that neutral collagenases also play a role in predigesting the osteoid layer and exposing the mineralized bone to osteoclastic activity. Here we show that gelatinase B (matrix metalloproteinase-9) is over-expressed in cholesteatoma compared to external ear canal skin (EACS). Expression of MMP-9 in cholesteatoma mainly occurs in suprabasal layers, and more rarely in basal layers of cholesteatoma epithelium, as well as in inflammatory cells of the perimatrix. We further analyzed the influence of cholesteatoma debris, cholesteatoma granulation tissue, and cholesteatoma components such as keratin, cholesterol and bacterial endotoxin on the expression of MMPs in EACS keratinocytes. We show that cholesteatoma debris and granulation tissue extract both induced the secretion of MMP-9 by EACS keratinocytes, while keratin. bacterial lipopolysaccharide (LPS) or cholesterol did not show any effect. We further performed co-incubation and immunoprecipitation experiments using neutralizing interleukin-1alpha, EGF, TGF-beta, TGF-alpha, interleukin-6 and TNF-alpha antibodies. Inhibition of MMP-9 up-regulation by debris or granulation tissue extract could be revealed with diverse cytokine antibodies. The results are discussed with regard to previously published studies.

Antibodies↗

[Second primary carcinomas in the upper aerodigestive tract in different locations and age groups].

BACKGROUND: Second primary tumors are of great importance for diagnostics, therapy and prognosis in patients suffering from squamous cell carcinomas of the upper aerodigestive tract. The clinical observation of an increase of second primaries was the reason for analyzing all patients with head and neck cancer treated for a certain period of time at our institution. METHODS: The hospital charts of 576 patients treated for squamous cell carcinoma of the oral cavity, the oropharynx, the hypopharynx and larynx treated from 1993 till 1996 at the Department of Otolaryngology, Head and Neck Surgery of the University of Würzburg were reviewed retrospectively. RESULTS: 10.1% of all patients developed a second primary tumor. The rate was highest for patients with carcinoma of the oral cavity (17.5%), followed by tumors of the hypo- and oropharynx (11.7% and 11.5%) and the larynx (6.4%). Besides the location, younger age was detected as a risk factor for the formation of second malignancies. The latency between first and second primary tumor was 2.9 years in average. 31% of the second primaries were detected synchronous, 39% metachronous. CONCLUSION: The results demonstrate that younger patients and patients with carcinomas of the upper digestive tract need a consequent follow-up. The development of second primaries even years after the first malignoma demonstrates the necessity of lifelong follow-up and oncological care.

Adult↗

[Molecular biology and immunohistochemical prognostic markers in head and neck squamous epithelial carcinomas].

BACKGROUND: Scientific research work of the last decade has been performed in order to investigate biological parameters of prognostic significance for head and neck squamous cell carcinoma. In contrast to other cancer types, like colon carcinoma, where tumour progression is accompanied by an almost defined sequel of gene activations and inactivations, cells of squamous cell carcinoma behave more heterogenously. METHODS: Publications concerning the most important immunohistochemical, molecular biological and cytogenetic prognostic markers in head and neck cancer have been analyzed. RESULTS: The prognostic markers discussed in this publication have been classified into the following areas: Apoptosis, cell cycle regulation, viral infections, cytokines and growth factors/growth factor receptors, angiogenesis and hypoxia, proteinases, cell-cell contacts and cell-matrix contacts, cytokeratin fragments, chromosomal rearrangements and genetically inherited susceptibility to toxic reagents. CONCLUSIONS: Significant prognostic markers are important for the clinical follow-up of patients and the choice of therapeutical approach. However, none of the factors analyzed can be used as an individual and universal prognostic marker at present.

Biomarkers, Tumor↗

Aflatoxin B1-induced mitotic recombination in L5178Y mouse lymphoma cells.

Aflatoxin B1 is a human hepatocarcinogen. It is also a known point mutagen in bacteria and mammalian cells. This mutagenic activity may be at least partly responsible for its carcinogenic activity. However, recent studies show that aflatoxin B1 induces mitotic recombination in the yeast Saccharomyces cerevisiae. Because numerous reports have implicated mitotic recombination in mechanisms leading to carcinogenesis and because no one has shown that aflatoxin B1 induces recombination in mammalian cells, we decided to examine the ability of aflatoxin B1 to induce recombination in a mammalian cell line. We used a combination of methods, analysis for loss of heterozygosity and whole chromosome in situ hybridization, to identify mechanisms of chromosome mutation, including mitotic recombination in the mammalian L5178Y mouse lymphoma cell system. Our experiments revealed that mitotic recombination caused approximately 60% or more of the aflatoxin B1-induced mutagenic lesions in this cell system. Thus, mitotic recombination plays an important role in aflatoxin B1-induced mutagenesis in mammalian cells and possibly in chemically induced mutagenesis and carcinogenesis. This work suggests that multiple genetic lesions may be involved in aflatoxin B1-induced pathology.

Aflatoxin B1↗

Detection of pharyngeal perforation: comparison of aqueous and barium-containing contrast agents.

OBJECTIVE: We sought to assess the value of aqueous and barium-containing contrast agents in the detection of pharyngeal perforation. SUBJECTS AND METHODS: Visual and objective in vitro comparisons of an iodinated aqueous contrast agent, a 50% weight/volume barium suspension, and a 100% weight/volume barium suspension were performed. Moreover, to exclude pharyngeal perforation after surgery, we prospectively examined 109 patients by pharyngography, using the aqueous contrast agent and the 100% weight/volume barium suspension. All patients with a pharyngeal perforation were followed up clinically to exclude complications due to barium application. RESULTS: As opposed to the 100% weight/volume barium suspension, in vitro comparison between the aqueous contrast agent and the 50% weight/volume barium suspension yielded no substantial differences. Seventeen perforations could be detected with the aqueous contrast agent. Although 10 of 17 perforations could be slightly better visualized with the 100% weight/volume barium suspension, two perforations were missed with this agent. Five perforations were equally well detected with both. CONCLUSION: Because of a higher radiopacity, 100% weight/volume barium suspensions may more sharply delineate perforations. However, in contrast to aqueous contrast media, narrow pharyngeal perforations can be missed. Thus, the use of a 100% weight/volume barium suspension does not improve the detection of pharyngeal perforation.

Adult↗