W. Bergler

Treatment of recurrent respiratory papillomatosis with argon plasma coagulation.

Extension of recurrent respiratory papillomatosis (RRP) to the lower airway in children is life-threatening and an extremely difficult condition to treat. We present the case of a seven-year-old girl with progressive RRP since the age of two. Repeated CO2 laser treatment and interferon-alpha treatment could not prevent tracheotomy and spread to the trachea. We used argon plasma coagulation (APC) with flexible endoscopy for the first time for the treatment of RRP. APC gives a controlled limited penetration into the tissue and good control of bleeding. There is no carbonization or vaporization which makes it a suitable method for the treatment of lower airway RRP. After a few treatments with APC, we gained very good control of the disease with no side-effects or complications. The described application of APC seems to be a promising way to treat lower airway RRP.

Serum levels of vascular endothelial growth factor in patients with head and neck cancer

Abstract Angiogenesis is now considered to be crucial for tumor growth and metastasis. In several tumors, microvascular density has been shown to be correlated with metastasis and aggressiveness. Vascular endothelial growth factor (VEGF) is a secreted endothelial cell-specific mitogen, which is induced by hypoxia and is angiogenic in vivo. VEGF has been identified in a wide variety of malignancies including head and neck squamous cell carcinomas (HNSCC). We investigated the circulating level of VEGF in sera from patients with various head and neck squamous cell carcinomas (n = 71) as well as from healthy normal controls (n = 47). Serum VEGF concentrations were determined as serum immunoreactivity by using a quantitative sandwich enzyme immunoassay technique. For statistical analysis, the Wilcoxon 2-sample test and Kruskal-Wallis test were performed. The majority of the patients with HNSCC were found to have high concentrations of serum VEGF. The levels of VEGF in the sera of patients with cancer ranged from below the detection limit to 937.1 pg/ml (mean, 144.5 pg/ml). In contrast, the VEGF serum levels in 47 healthy individuals ranged from below the detection limit to 168.1 pg/ml (mean, 32.7 pg/ml), VEGF serum concentration being significantly higher in HNSCC patients (P = < 0.001). These findings indicate that a positive angiogenesis regulator such as VEGF might function as an endocrine growth factor, particularly for solid HNSCC tumors and may be a useful marker for clinical monitoring.

Control of blood pressure, heart rate and haematocrit during high-dose intravenous paraoxon exposure in mini pigs

A therapeutic regimen was established to keep blood pressure, heart rate and haematocrit within the normal range during high‐dose paraoxon (PX) exposure (ca. 150 × ld50) in mini pigs in order to achieve survival. Previous experiments showed that mini pigs exposed to high‐dose PX died shortly after PX infusion due to hypertension, tachycardia and increased haematocrit if no antihypertensive and fluid therapy was initiated. Therefore, antihypertensive and fluid therapy with magnesium (MgSO4) and Ringers solution was established to keep the blood pressure, heart rate and haematocrit within a pre‐established normal range.

The expression of epidermal growth factor receptors in the oral mucosa of patients with oral cancer

SummaryRepresentative tumor samples and mucosal samples were taken from three different groups of patients and were stained immunohistochemically for their expressions of epidermal growth factor receptors (EGFR). Patients in group 1 had oral squamous carcinoma, with specimens taken from the tumor as well as from the mucosa without tumor invasion. Patients in group 2 had no evidence of tumor but had heavy drinking and smoking habits. Tumor-free patients who do not drink or smoke served as the control group. The findings in the present study showed that the tumor and mucosal samples from groups 1 and 2 had increased EGFR expression while the control group showed significantly less EGFR. These results suggest that EGFR may play a role in the development of premalignant tissue changes, which are probably influenced by chronic toxic irritation.

Current advances in the basic research and clinical management of juvenile-onset recurrent respiratory papillomatosis

Abstract Juvenile-onset recurrent respiratory papillomatosis is a relatively uncommon disease that presents clinically with symptoms ranging from hoarseness to severe dyspnea. Human papilloma viruses type 6 and 11 are important in the etiology of the papillomata and are most probably transmitted from mother to child during childbirth. Although spontaneous remission is frequent, a rare fatal course because of pulmonary spread or malignant transformation has occurred. CO2 laser evaporation of papillomas and adjuvant drug therapy using lymphoblastoid α-interferon are the most common treatment modalities at present. However, several other treatment modalities have been tried with varying success. Recent advances in basic research and different therapeutic approaches are reviewed.

Idiopathic chronic hiccup: combination therapy with cisapride, omeprazole, and baclofen

Idiopathic chronic hiccup (ICH) is defined as recurring hiccup attacks that last for longer than an arbitrary time limit (eg, 1 month) and for which no organic cause can be found. In patients with ICH, therapy is largely empiric. For practical purposes, idiopathic hiccup can be assumed to have its origin either in the viscera (gastrointestinal tract) or in the central nervous system. Cisapride and omeprazole--through reduction of gastric acid production and facilitation of gastric emptying, respectively--are thought to reduce an assumed afferent input from the periphery to a putative supraspinal hiccup center. Baclofen is thought to reduce excitability and depress reflex hiccup activity. Fifteen male patients (mean [+/- SD] age, 68.2 +/- 11.6 years) who had recurring hiccup attacks for a mean duration of 100.8 +/- 134.1 months (range, 12 to 564 months) were treated for ICH with a combination of cisapride, omeprazole, and baclofen (COB). Therapy led to a total disappearance of hiccup in 40% (6 of 15) of the treated patients. An additional 20% (3 of 15) of patients experienced substantial relief. A Mann-Whitney rank order test showed a highly significant reduction in the severity of the hiccup attacks as reflected in the subjective assessment scale scores taken before therapy (8.6 +/- 1.3) compared with those taken after 20 weeks of therapy (4.1 +/- 3.8). Thus we concluded that COB is an effective empiric therapy in at least some patients with ICH.

Der Mallampati-ScoreVorhersage der schwierigen Intubation in der HNO-Laserchirurgie mittels Mallampati-Score

ZusammenfassungDer Mallampati-Score ist eine gebräuchliche Methode zur Vorhersage der schwierigen Intubation. Wir testeten seine Validität in der HNO-Laserchirurgie. Methoden: Bei 91 Patienten, die sich einem geplanten laserchirurgischen Eingriff in der HNO unterziehen mußten, wurde unmittelbar vor der Narkoseeinleitung der Mallampati-Score in der Modification nach Samsoon u. Young [18] ermittelt. Nach Narkoseeinleitung wurde die laryngoskopische Sicht nach Cormack u. Lehane [5] beurteilt. Es wurde untersucht, inwieweit ein Mallampati-Score ≥3 eine schwierige Intubation (d.h. einen Cormack u. Lehane-Grad ≥3) vorhersagt. Ergebnisse: 62 Patienten hatten einen Mallampati-Score ≤2. Von diesen hatten 4 (=6%) einen Cormack u. Lehane-Grad ≥3.29 Patienten hatten einen Mallampati-Score ≥3. Von diesen hatten 6 (=21%) einen Cormack u. Lehane-Grad ≥3. Schlußfolgerung: Dieser Unterschied war signifikant im χ2-Test (p<0,05). Patienten mit einem Mallampati-Score ≥3 waren also signifikant häufiger schwierig zu intubieren. Niedrige Sensitivität (60%) und Spezifität (72%) begrenzen jedoch den praktischen Wert des Tests.AbstractThe Mallampati score (MS), later modified by Samsoon and Young, is a common method used to predict difficult intubation. We tested its predictive value in otolaryngologic (ENT) laser surgery. Methods: Ninety-one patients scheduled for elective ENT laser surgery had the modified MS noted prior to induction in the supine position, with the tongue fully protruded and phonating ”ah”; 22 patients were female, 69 male. The mean age was 54±15 (6–84) years, height 171±9 (130–190) cm, and weight 72±21 (20–99) kg. After a standard induction, the laryngoscopic view was graded according to Cormack and Lehane (C&L). An intubation was considered difficult if the C&L score was ≥3, i.e., no part of the glottis seen during laryngoscopy. The hypothesis tested was that a MS ≥3 (i.e., only the base of the uvula or nine of the uvula was seen) is predictive of difficult intubation in this group of patients. This chi-square test was used for calculation of significance. Results: All intubations were performed in less than three attempts, and no C&L score of 4 (i.e., not even the epiglottis seen during laryngoscopy) was observed; 10 patients had a C & L score ≥3, i.e., a difficult intubation according to our definition. Sixty-two patients had a MS ≤2; of these, 4 (=6%) were difficult to intubate. Twenty-nine patients had MS ≥3; of these, 6 (=21%) were difficult to intubate. This difference was significant (chi-square=4.1, P<0,05). Conclusion: Difficult intubation was significantly more common in patients with MS ≥3. Low sensitivity (60%) and specificity (72%) limit the clinical value of this test, however.

Tonsillektomie mit dem Argon-Plasma-Koagulations-Raspatorium

ZusammenfassungHintergrund: Die Argon-Plasma-Koagulation (APC) bietet eine innovative Möglichkeit eine Tonsillektomie durchzuführen. Wie sich diese Hochfrequenzchirurgietechnik von konventionellen Tonsillektomieverfahren unterscheidet, soll anhand einer Studie untersucht werden. Patienten und Methode: In einer klinisch-prospektiven randomisierten Blindstudie mit 133 Patienten wurde die APC-Tonsillektomie (TE-APC) mit der stumpfen Dissektion, mit Kompression und bipolarer Koagulation zur Primärblutstillung (TE-konv), verglichen. Ergebnis: Der intraoperative Blutverlust und die durchschnittliche Operationsdauer waren bei der TE-APC signifikant erniedrigt (p<0,01). Kein signifikanter Unterschied lies sich bei dem postoperativen Schmerz, der Otalgia und der aufgetretenen Nachblutungen zwischen den beiden Verfahren feststellen. Bei der TE-APC kam es zu vermehrter Fibrinbelagausbildung und an einzelnen postoperativen Tagen zu einem geringfügig erhöhten Analgetikaverbrauch. Schlußfolgerung: Bei der TE-APC erfolgten Dissektion und Koagulation in einem Schritt, dadurch wurde die Operationsdauer signifikant verkürzt. Durch den selbstlimitierten Effekt der Gewebepenetration der APC wird eine kontrollierte Eindringtiefe in das Gewebe erreicht. Die bei elektro- und laserchirurgischen Techniken üblicherweise festzustellende ausgeprägte postoperative Schmerzsymptomatik fand sich bei der APC-TE nicht.SummaryBackground: The Argon-Plasma-Coagulation (APC) offers an innovative possibility for the tonsillectomy combined with a high-frequency technology. Aim of our study was to inves-tigate the differences between this high-frequency-technology and the traditional tonsillectomy. No reports exist in the use of the APC in the tonsillectomy. Methods: Argon-Plasma-Coagulation tonsillectomy (TE-APC) was compared with the traditional blunt dissection tonsillectomy (TE-trad) with hemostasis by compression and bipolar coagulation. 133 patients were stratified in two age groups in a clinical prospective randomised study. Results: Average surgical time and blood loss were markedly decreased in the TE-APC group (p<0,01). There was no significant difference between the two techniques concerning postoperative pain, otalgia, and primary or secondary haemorrhage. In the TE-APC group more extensive fibrin layer appeared after surgery. In the TE-APC patients’ group, there was a slightly higher consume of analgetics in some postoperative days. Conclusions: The one-step dissection and coagulation procedure leads to an almost bloodfree woundground and to a reduction of operation-time. The self-limited and effective coagualative properties of the APC-method leads to a controlled penetration depth. The often associated extensive post operative pain and uncontrolled tissue- damage, known from electrical and lasersurgical techniques, was not found in TE-APC-patients-group.

Establishment and characterization of cisplatin-Resistant sublines of the human squamous carcinoma cell line HLac 79

Though various chemotherapy protocols lead to considerable response rates in squamous cell head and neck cancer (SCHNC), the overgrowth of a tumor cell phenotype which no longer responds to clinically achievable drug concentrations regularly impairs definite tumor control. In order to investigate mechanisms of drug resistance towards one of the most active agents in SCHNC we established four Cisplatin (CDDP)-resistant sublines (DDP1-DDP4) of the recloned human SCHNC cell line HLac 79. The 50% inhibitory drug concentration (IC50) of CDDP as determined by the colorimetric MTT-assay was increased by the factors 2.7 (DDP1), 3.3 (DDP2), 5.1 (DDP3), and 6.4 (DDP4) in the respective sublines. Three subpopulations contained significantly elevated glutathione (GSH) levels by the factors 1.4 (DDP3), 1.7 (DDP2), and 2.4 (DDP4) compared to the maternal line (50.2 nM/mg protein). DDP4 showed increased activity of gamma-glutamyl-transpeptidase (1.83 vs. 1.21 mU/mg protein), and DDP2 and DDP4 showed increased activity of GSH-S-transferase (35.6 and 51.9 vs. 25.1 mU/mg protein). Concerning both GSH-peroxidase and GSH-reductase no significant differences between the HLac 79 subpopulations were observed. Intracellular CDDP accumulation determined by neutron activation analysis revealed reduced drug uptake in DDP3 and DDP4 (60% and 76% of control value).

A new histobiochemical method to analyze sialylation on cell-surface glycoproteins of head and neck squamous-cell carcinomas

Oncogenic transformation is often accompanied by alterations of glycosylation on a tumor cells surface, which may contribute to uncontrolled cell growth. The sialoglycans and degree of sialylation on the cell surface are of increasing interest because of their possible role in metastasis and tissue invasion. Since primary tumors and metastases may differ in the degree of sialylation, we examined the expression of sialic acid as a terminal constituent of lactosaminyl glycans on the cell surfaces of 30 cervical lymph-node metastases and 30 squamous-cell carcinomas of the oropharynx and oral cavity. Cell-surface sialylation was determined by a new histobiochemical assay on cryostat sections and was based on the enzymatic introduction of a fluorescence-labelled sialic acid into lactosaminyl type (Gal-β 1–4 G1cNAc) oligosaccharide chains of cell-surface-expressed glycoproteins. To this end, tissues were incubated in the presence of 5-acetamido-9-deoxy-9-fluoresceinyl-thioureido neuraminic acid (CMP-9-fluoresceinyl-NeuAc) and α-2,6-sialyltransferase. In order to compare the degree of sialylation with the potential total amount of sialylation sites, pretreatment with sialidase for desialylation was required. We observed a significantly higher amount of lactosaminyl-type binding sites for sialic acid on metastases compared to the primary tumors (P = 0.001), indicating a lower degree of sialylation in metastases. In primary tumors no correlation was seen between the amount of binding sites and tumor localization, TNM stage or histologic grading. Pretreatment of specimens with sialidase demonstrated a significant degree of sialylation on both primary tumors and lymph-node metastases, but no difference between primary tumors and metastases. When tumor stroma of primary tumors and metastases was compared, tumor cells showed a higher degree of free binding sites for sialic acid, but a low degree of sialylation. Our results suggest that differences in the degree of sialylation of glycoconjugates on a tumor cells surface may play an important role in the process of cell metastasis. Our histobiochemical method turned out to be very reliable, effective and readily performed.