[Show abstract][Hide abstract] ABSTRACT: Head and neck squamous cell carcinomas (HNSCC) represent a group of metastasizing tumors with a high mortality rate in man and animals. Since the biomolecule ozone was found to inhibit growth of various carcinoma cells in vitro we here applied the highly aggressive and lethal VX2 carcinoma HNSCC tumor model of the New Zealand White rabbit to test whether ozone exerts antitumorous effects in vivo. Therapeutic insufflation of medical ozone/oxygen (O(3)/O(2)) gas mixture into the peritoneum (O(3)/O(2)-pneumoperitoneum) at an advanced stage of tumor disease led to a survival rate of 7/14 rabbits. Six of the seven surviving rabbits presented full tumor regression and the absence of local or distant lung metastases. Insufflation of pure oxygen (O(2)) resulted in a survival rate of 3/13 animals accompanied by full tumor remission in 2 of the 3 surviving animals. Of the 14 sham-treated animals only 1 had spontaneous tumor remission and survived. No adverse effects or changes in standard blood parameters were observed after repeated intraperitoneal insufflations of the O(3)/O(2) or O(2) gas. Animals with O(3)/O(2)-induced tumor eradication developed tolerance against reimplantation of the VX2 tumor. This could be reversed by immune suppression with a combination of dexamethasone and cyclosporin A suggesting an antitumorous effect of O(3)/O(2)-mediated activation of the body's own immunosurveillance. Although the exact mechanisms of action are still unclear the present data point to O(3)/O(2)-pneumoperitoneum as a promising new strategy in anticancer therapy.
Full-text · Article · May 2008 · International Journal of Cancer
[Show abstract][Hide abstract] ABSTRACT: The presence of lymph node metastases relevantly and significantly impairs disease-specific survival in patients suffering from squamous cell carcinoma of the upper aerodigestive tract. In a VX2 animal tumor model, we present an interstitial translymphatic therapeutic approach using cis-diaminedichloro-platinum(II) (CDDP) conjugated to a poly(ethylene oxide)-block-poly(lysine) (PEO-b-PLys) block copolymer tracking systems for the successful treatment of lymph node metastases. Most effective was the application of a high cargo-load CDDP tracking system (48 wt. % CDDP) curing 90% of the animals and causing only minor local side-effects. Systems containing 1 or 10 wt. % of CDDP were less effective but still cured 50% of the animals. Moreover, the administration of 1 or 10 wt. % of CDDP consistently limited tumor growth to the draining lymph nodes (50%) and prevented systemic distribution of the metastasis even'with 1 wt. % CDDP load. The systems contained 0.25-0.003 mg/kg per body weight CDDP compared to 1 ml/kg per body weight as usually used for intravenous administration. This approach encourages further and more detailed research of a CDDP-based interstitial translymphatic administration of chemotherapy for lymphogenic metastasizing carcinomas in different body regions.
Full-text · Article · Nov 2007 · Anticancer research
[Show abstract][Hide abstract] ABSTRACT: The surgical procedure for patients with otosclerosis routinely is incus stapedotomy. In case of otosclerosis with incus necrosis or a bony fixation of the malleus and incus, malleostapedotomy is performed.
Between May 2002 and September 2003, malleostapedotomy was performed in 6 out of 34 patients with otosclerosis. In 2 primary cases, a middle ear dysplasia was found. The malleus was fixed in 2 further primary cases. Two revision surgeries were performed with incus necrosis present. A titanium piston was used, which was fixed at the malleus handle and introduced into an opening of the footplate.
The preoperative air-bone gap was reduced from 36 dB(A) to 13 dB(A) after surgery for an average checkup time of 3 months. The length of the prostheses varied from 6.3 to 7.5 mm. No patient showed a hearing loss or vertigo after surgery.
Malleostapedotomy is the technique of choice in case of an additional pathology of the ossicular chain in patients with otosclerosis. Larger numbers of patients and long-term investigations need to compare the results of malleostapedotomy with those of a conventional incus stapedotomy.
No preview · Article · Feb 2007 · Advances in oto-rhino-laryngology
[Show abstract][Hide abstract] ABSTRACT: For patients with cancer of the upper airways and food canal, the demonstration of lymphogenic metastases is the most important prognostic factor for survival, which is significantly reduced depending on the number of regional lymph node metastases. Thus, the treatment of regional lymph flow (neck dissection) is a primary surgical procedure among the therapeutic options. For multimodal therapy concepts this is also true for radiochemotherapy. Various problems can be determined from literature based data: the studies use different radiochemotherapeutic protocols as well as various times between radiochemotherapy and neck dissection. Indications for neck dissection remain unclear as do those for the extent of the dissection. Published data provide only partial or no statements on N-status, tumor localization, stage distribution, etc. In addition, only incomplete information on the correlation between pre- and postoperative neck status as well as imaging diagnostics and postoperative histologically verified results is available. When considering the histopathological results, standards are lacking, and the question of when a cell is neither apoptotic nor necrotic but is still capable of proliferation and metastasis is not clearly answered.
[Show abstract][Hide abstract] ABSTRACT: Little is known about the effectiveness of clinical courses as a learning environment. To accurately assess performance in these courses, equal conditions for all candidates are required. We investigated the influence of the proximity of the course to the students test taking, the students' learning styles, and their self-motivation for learning in relation to performance success. One hundred and eleven students were randomized into eight groups, each attending a 2 week course in otolaryngology with a high proportion of patient-related teaching, and a 2 week long course in neurology with a low level of patient-related teaching. All students took multiple-choice end-of-term exams to assess their knowledge in both subjects. There was a different time interval between the course participation and the test taking for each of the groups. Performance success was correlated with the different groups, as well as with the type of learning style (LIST questionnaire) and with motivation for learning (study interest questionnaire). Explorative rank variance analysis showed a significant correlation between students' performance on the written exam and the time interval between completion of the neurology course and test-taking, with the shortest interval corresponding to highest scores (P = 0.002). There was no such effect on the success rate in otolaryngology (P = 0.28). Study motivation was not the major component for performance success, but a strong correlation between the use of strategic and deep learning styles and success in the exam was observed (R = 0.62; P < 0.001). The duration of time between a clinical course with little practical teaching and the students' taking of the exam plays a significant role on performance success; this effect does not occur in a course with a high proportion of practical patient-related teaching. More studies on clinical courses are needed to establish how students can be given adequate opportunities to develop necessary skills for patient care and for objective success on assessment. With such further information, the effectiveness of clinical courses as a learning experience might be enhanced.
No preview · Article · Nov 2006 · Archiv für Klinische und Experimentelle Ohren- Nasen- und Kehlkopfheilkunde
[Show abstract][Hide abstract] ABSTRACT: Two centre based evaluations of oncologic results of endoscopic resection of supraglottic cancer without post-operative irradiation.
Twenty-six patients with clinical T1 (n=5) or T2 (n=21) primary squamous cell carcinomas of the supraglottic larynx and with N0 (n=24) or N1 (n=2) neck disease were treated by endoscopic supraglottic laryngectomy coupled with neck dissection(s). Endoscopic resection was standardized whereas neck dissections (NDs) varied from classical modified radical ND to selective ND of levels I to IV.
Pathologically, three T2 patients were upstaged to T3, four N0 patients to N1 and one N2 patient down-staged to N1. Within an average of 42 months, there were no local failures and only one regional failure.
Endoscopic resection of T1 and T2 supraglottic cancer without post-operative irradiation achieved good oncological results. No patients with lateralized primary cancers were found to have contralateral cancer on pathological evaluation from bilateral dissections.
No preview · Article · Oct 2006 · The Journal of Laryngology & Otology
[Show abstract][Hide abstract] ABSTRACT: To assess the risk factor of capsular rupture for individual prognosis and potential therapeutic decision making, the present meta-analysis elaborated the prognostic significance of perinodal spread in a large group of patients suffering from head and neck squamous cell carcinomas (HNSCC). A review of the published literature was conducted, and fixed and random effects models were applied for estimation of the summarised odds ratio and 95% confidence intervals, including a test for homogeneity of the odds ratios. Study methodology allowed the enrollment of only nine studies of 115 published papers. Excluded studies lacked regarding primary tumour location, number and location of lymph node metastases, values on five-year survival, or adequate follow-up data. A summarised odds ratio of 2.7 leads to the conclusion that perinodal spread negatively impacts the five-year survival. The lower confidence limit of more than 2 also supports the concept that perinodal spread significantly reduces (doubled risk) the five-year-survival. These results support the conclusion that perinodal spread is a significant adverse risk factor for survival in patients with HNSCC.
No preview · Article · Sep 2006 · European Journal of Cancer
[Show abstract][Hide abstract] ABSTRACT: Cancer of the larynx in elderly patients should be treated with curative intention, if the extension of the primary tumour allows safe resection. Transoral CO(2) laser microsurgery is associated with a low rate of major complications and can be regarded as suitable even for elderly patients. Age itself should never be the sole factor in deciding which therapy should be undertaken.
In the industrialized nations the age group beyond 75 years will grow steadily, requiring special attention by medical professionals in the future. Nowadays laryngeal cancer is often treated by transoral CO(2) laser microsurgery. Because of a variety of comorbidities, the incidence of perioperative complications in the group of elderly patients is of increasing interest. To date, no references in the literature have discussed complications after transoral CO(2) laser microsurgery in this age group. Patients and methods. Twenty-four patients over the age of 75 suffering from squamous cell carcinoma of the larynx and treated by transoral CO(2) laser microsurgery since 1998 were analysed for intraoperative and postoperative complications.
There was no evidence of surgery-related complications at all. Postoperatively, 6 of 24 patients complained about dysphagia. Due to intraoperative placement of nasogastric feeding tubes in these six cases further complications such as pneumonia resulting from aspiration could have been avoided.
No preview · Article · Jun 2006 · Acta Oto-Laryngologica
[Show abstract][Hide abstract] ABSTRACT: Plakophilins (PKPs) are a set of 3 constitutive armadillo repeat proteins of the desmosomal plaque, termed PKP 1, PKP 2, and PKP 3, which have been shown to be functionally relevant for desmosomal adhesion. We have performed a systematic immunohistochemical study of the 3 PKPs in oral and pharyngeal squamous cell carcinomas (SqCCs; n = 40); colorectal, pancreatic, and prostate adenocarcinomas (n = 31), and hepatocellular carcinomas (HCCs; n = 8). In SqCCs, PKP 1 and PKP 3 revealed common desmosome-type immunostaining, their expression level being inversely correlated with the degree of malignancy. Instead, staining for PKP 2 was limited. In contrast, all adenocarcinomas contained PKP 2 and-often abundantly-PKP 3 in desmosome-typical pattern, whereas PKP 1 was expressed only in prostate tumors. The presence of PKP 3 in adenocarcinomas was confirmed by immunoblotting. In HCCs, only PKP 2 was detected. Under certain staining conditions, focal nuclear immunoreactivity for PKP 1 was observed in some SqCCs and HCCs. Our results, which are inconsistent with previously published data to some extent, indicate a principal preservation of the cell type and differentiation-related expression patterns of PKPs in normal epithelia. For PKP 1, a suppressor function of malignant behavior seems conceivable, whereas the putative functional significance of its occurrence in tumor cell nuclei requires further studies.
[Show abstract][Hide abstract] ABSTRACT: Currently the significance of the sentinel node (SN) biopsy also for head and neck cancer is discussed intensively. Based on the complex anatomic structures of this region with a low distance between primary and sentinel node as well as approximately 300 lymph nodes an intensive discussion of the methodical basis of sentinel node detection seems to be essential. Thus it was the aim of the present study to examine the detection spectrum of a gamma probe for identification of cervical lymph nodes using an in vitro model to describe and objectify the particularities of measurement existing in the head and neck region.
In an in vitro model the detection spectrum of a gamma probe is examined in 29 different series of measurements (variation of the specimen filled with 99m pertechnetat regarding activity, position, collimator distance, tissue sheath).
The presented in vitro model reflects the clinical problem of narrow intranodal activity of neighbouring lymph nodes and reveals a direct relation between the number of radiation sources and their isolated evidence. Using muscle tissue with a thickness of 0.4 cm, two two-rowed radiation sources, the more powerful is placed 1.5 cm behind the other specimen, with a lateral difference of 3 cm, can be resolved only with a maximal detector distance of 1 cm. Not the difference of the tissue but the thickness of the tissue is decisive for detection.
Especially for pharyngeal and laryngeal lymph nodes a transcutaneous measurement reflecting the exact localisation of hot nodes in the area of the deep jugular lymph nodes is not possible with increasing tissue thickness. The described results require a critical discussion of the different detection techniques varying among the different working groups of this field.
No preview · Article · Feb 2006 · Otolaryngologia polska. The Polish otolaryngology
[Show abstract][Hide abstract] ABSTRACT: Radiofrequency-induced thermotherapy has shown promising results in the palliative treatment of various tumor entities. The purpose of this study was to investigate the effectiveness of bipolar radiofrequency volumetric tissue reduction (VTR) on lymph node (LN) metastases in the VX2 SCC model.
Six male New Zealand white rabbits, with palpable metastatic disease within the parotid lymph nodes, were treated using the Celon-ProSurge probe, needle length 10 mm, diameter of 2.3 mm. The animals were sacrificed on the 4th, 8th, 11th, 14th, 18th and 22nd postoperative days respectively.
Bipolar radiofrequency VTR could prevent progression of local metastatic disease in one-third of the animals compared to the control group of untreated VX2 carcinoma rabbits. These results encourage further studies, directed at whether this treatment modality could play a role in the palliative therapy of metastatic LN. Future studies should concentrate on the refinement of the treatment parameters and optimization of the treatment duration.
Full-text · Article · Nov 2005 · In vivo (Athens, Greece)
[Show abstract][Hide abstract] ABSTRACT: The role of the single matrix metalloproteinases (MMPs) in the metastatic process of squamous cell carcinomas (SCC) is still obscure.
The MMP-9 expression was described immunohistochemically in 105 patients (40-79 years of age, mean: 57.84 years; 84 male, 21 female) suffering from orophatyngeal cancer (22x TI, 31x T2, 24x T3, 28x T4) with different neck stages (41x N0, 6x N1, 54x N2, 4x N3 neck).
A significant correlation between MMP-9 expression and T stage (p < 0.05), N stage (r = 0.55, p < 0.01) and UICC stage (r = 0.55, p < 0.01) was revealed. Most remarkable was the high MMP-9 expression with simultaneously high UICC stages.
The results give further indication that MMP-9 plays a role in the metastatic behavior of oropharyngeal SCC. It will be a project for the near future to create a standardized evaluation score of immuno-histological stainings to allow valid comparison of the results and published data.
Full-text · Article · Nov 2005 · Anticancer research
[Show abstract][Hide abstract] ABSTRACT: The aim of the study was to test the feasibility of resection of VX2 auricular squamous cell carcinoma (SCC) in New Zealand White rabbits (NZW), its influence on the regional and distant metastases and the general prognosis.
In 71 NZW rabbits, successful in sano wide margin resection of auricular VX2 SCC was performed 7 days after tumor induction. The animals were sacrificed and examined for metastases after 6 weeks.
Local recurrences occured in 7% of the animals. In 28.2% lymph node (LN) and in 15.5% distant metastases developed. Regional metastases presented in 100% of the animals with recurrence and in 22.7% of the RO animals (p < 0.001). Distant metastases presented in 80% of the animals with local recurrence and in 10.6% of the R0 animals (p < 0.001). Of the animals with local control, those with N+ had a significantly higher incidence of distant metastases (46.7%) compared to those with N0 (0%, p < 0.001). Local control and LN involvement were found to be important prognostic factors for early tumor-related death.
The VX2 auricular model resembles head and neck (HN) SCC in humans morphologically, pathophysiologically and as a complex neoplastic disease. In the experimental setting it behaved similarly to the clinical situation of wait-and-see in N0 HNSCC patients. Tumoral microemboli present a possible mechanism for the development of recurrences.
Full-text · Article · Nov 2005 · Anticancer research
[Show abstract][Hide abstract] ABSTRACT: Head and neck squamous cell carcinomas (HNSCC) are the most frequent malignancies of the upper aerodigestive tract. Cisplatin resistance is a major problem in the treatment of a large number of HNSCC cancer patients. In this study, nine randomly selected HNSCC cell lines were investigated regarding expression, presence of mutations, nucleocytoplasmic distribution of p53, and sensitivity to cisplatin.
Protein expression was evaluated by Western blot analysis. The whole open reading frame of p53 was determined by reverse transcription-PCR sequencing. Nucleocytoplasmic distribution was evaluated by confocal laser scanning microscopy. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide viability assay was used to test for cisplatin sensitivity.
p53 mutations were found in all nine investigated HNSCC cell lines. Nuclear p53 signal was detected in six cell lines, whereas three cell lines exhibited total loss of nuclear p53 signal. Nuclear signal depended on the presence or absence of the COOH-terminal nuclear localization signal in p53. Cisplatin sensitivity was highly reduced in the group with loss of nuclear p53 signal compared with those with detectable nuclear signal. Transfection of wild-type and mutant p53 into a rat embryonic cell system showed highly reduced activity of the nuclear localization signal mutant p53 protein.
Taken together, these data suggest that "loss of nuclear p53 signal" correlates with cisplatin resistance in HNSCC. If these results can be validated on a larger number of tumor samples, including fresh tumor tissues, it potentially could help in sparing a subgroup of HNSCC patients the side effects associated with unnecessary chemotherapy by identifying cisplatin nonresponders before chemotherapy induction.
No preview · Article · Nov 2005 · Clinical Cancer Research
[Show abstract][Hide abstract] ABSTRACT: The purpose of this manuscript is to give a cost-effectiveness analysis of the photodynamic therapy by means of Foscan (Foscan-PDT) in Germany. The basis for this paper is provided by a study performed in Great Britain which analyses the costs of Foscan-PDT compared to the costs of palliative chemotherapy and to the option of no treatment in patients with advanced head and neck cancer.
In order to calculate the cost-effectiveness, an already published model developed on the base of English data was fed with German cost-data. For consideration of the different characteristics of cost-parameters as well as to minimize the over- or underestimation of the costs, sensitivity analyses were performed.
The Foscan-PDT revealed the highest health-related effectiveness compared to all other above-mentioned options -- 129 additional days of life in comparison to no treatment or 48 days in comparison to four cycles of palliative chemotherapy. The costs per therapy of Foscan-PDT ( 8,761 euros) were lower than those of four cycles of palliative chemotherapy (11,600 euros).
Foscan-PDT is a cost-effective treatment option for patients suffering from advanced head and neck cancer. For patients who up to now had only very limited treatment possibilities at their disposition, Foscan-PDT offers a chance for reduction of the tumor, remission, and a prolonged expectancy of life.
No preview · Article · Nov 2005 · Laryngo-Rhino-Otologie
[Show abstract][Hide abstract] ABSTRACT: The expressions of MMP2, -7, -9, -13 and TIMP1, -2, -3 were examined in biopsies and cell lines of head and neck squamous cell carcinomas (HNSCC) to determine the association between the expression profile and TNM-staging of the primary. The expressions of MMP2, -7, -9, -13 and TIMP1, -2, -3 were analyzed in 30 HNSCC biopsies, 7 HNSCC cell lines and 1 keratinocyte cell line using RT-PCR. Negative correlation was determined between N-status and MMP13-RNA expression [Kendall-tau-b -0.404 (p = 0.016), Spearman-rho -0.448 (p = 0.014)], histological grading [Kendall-tau-b -0.291 (p = 0.049), Spearman-rho -0,333 (p = 0.048)], and MMP7 and TIMP2 expression [Kendall-tau-b -0.318 (p = 0.045); Spearman-rho -0.353 (p = 0.045)]. Positive correlation was determined between M-status and MMP9-RNA expression [Kendall-tau-b 0.341 (p = 0.025), Spearman-rho 0.377 (p = 0.024)] and MMP13 and TIMP2 expression [Kendall-tau-b 0.727 (p = 0.037), Spearman-rho 0.850 (p = 0.016)]. The results point to a role of the tested MMPs and TIMPs in the metastatic spread of HNSCC.
Full-text · Article · Sep 2005 · In vivo (Athens, Greece)
[Show abstract][Hide abstract] ABSTRACT: The objective of the current metaanalysis was to evaluate the expression patterns of matrix metalloproteinases (MMPs) in patients with head and neck squamous cell carcinoma (HNSCC), to evaluate reported series, and to determine whether there is an expressed value to quantitate the risk of metastasis.
A review of the published literature was conducted according to defined selection criteria. Fixed and random effects models were applied for estimation of the summarized odds ratio and 95% confidence intervals, including a test for homogeneity of the odds ratios of the studies. Finally, forest plots were created to allow for visual comparison of the results and an estimation of heterogeneity.
The heterogeneity of data collection and statistical methods did not allow final judgments on the significance of immunohistochemical MMP expression analysis in patients with HNSCC or the impact of MMPs in predicting metastatic behavior. Fourteen studies with 710 patients for 5 different MMPs (MMP-1, MMP-2, MMP-3, MMP-9, and MMP-14) were included in the current metaanalysis. The results indicated that MMP-2, MMP-3, MMP-14 possibly played a role in the metastatic behavior of HNSCC tumors.
The authors recommended the standardization of staining procedures and evaluation protocols as a necessary step to allow for valid comparisons of the multitude of results published by different study groups.
[Show abstract][Hide abstract] ABSTRACT: Cytokeratins (CK) are members of intermediate filaments, which are predominantly found in epithelial cells. Different types of epithelia are characterized by a distinct composition of CK. Recently immunohistochemical investigations demonstrated that, among others, CKs 6, 14, 16 and 17 are regularly expressed in benign stratified squamous epithelium of the head and neck as well as in squamous cell carcinoma of the head and neck (HNSCC) in contrast to CKs 1, 10 and 11, that were only rarely expressed in these tissues.
Total RNA was isolated from 15 primary cell lines derived from HNSCC and from 15 tissue samples of oro- and hypopharyngeal carcinomas obtained from surgery specimens. CK expression was evaluated by RT-PCR, Western blot analysis and immunohistochemistry.
CK6 and 16 were found to be expressed in both groups at almost 100%. The expression level of CK14 remained constant (73%) in both groups, at the RNA and protein level. CK17 was more frequently present in tumour specimens than in HNSCC cell lines. The immunohistochemical results of the surgical tumour specimens confirmed the results of Western blot analysis.
The presented results show high and stable expression rates for CK6 and CK16 in HNSCC. These results will serve as a basis for further investigations concerning the search for circulating tumour cells and micrometastases. In addition, we found that cytokeratin expression in HNSCC is different on the RNA level compared to the protein level.
Full-text · Article · Jul 2005 · Anticancer research