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Objective: Imidazoline derivatives like naphazoline have a firm place in diagnostics and therapy of otorhinolaryngology because of their vasoconstrictive and decongestive properties. Their alpha-adrenergic potential could induce not only local but also systemic side effects like hypertension and tachycardia which can increase a life-threatening intoxication. Signs of imidazoline intoxication are excessive systolic and diastolic hypertension and hypotension, bradycardia with arrthyhmia, respiratory depression, excitation or severe CNS depression. Patients: The typical course of an intoxication and its sufficient therapy is reported by means of two cases of intraoperative application of naphazoline for hemostasis. Results: In case of overdosage or intoxication, symptomatic drug therapy with intravenous administration of 5 mg phentolamine for adults and 1 mg phentolamine for infants has to be done. Phentolamine, an alpha-adrenoceptor antagonist, acting against peripheral and central side effects has to be used because no specific antidote is available. Conclusions: Especially pediatric otorhinolaryngologists have to know about symptoms and therapy of an intoxication after application of naphazoline. Particularly with children, a narrow therapeutic to toxic window can be observed in this frequently used drug.

Tumor oxygenation is well recognized as a major factor of tumor response to radiotherapy. In this respect, a number of studies have examined the response of primary tumors, whereas little is known about the oxygenation of tumor recurrences after radiotherapy. It was the aim of this study to investigate the oxygenation of tumor recurrences after preceding irradiation of the primary tumor.Tumor oxygenation in primary tumors and recurrences of rat rhabdomyosarcomas R1H was measured by using pO(2) probes and Eppendorf pO(2) histography. Primary tumors were irradiated at a (60)Co radiotherapy facility with a total dose of 75 Gy, given in 30 fractions over 6 weeks. Oxygenation was measured in R1H tumors before and directly after completion of irradiation. In R1H recurrences oxygenation was determined, when they reached the same size as the previously treated primary tumors (V(o) = 3.1 +/- 0.5 cm(3)). Additionally, tumor microvessel density and the intercapillary distance of tumor blood vessels were determined on histological sections using a counting grid.Tumor oxygenation in R1H recurrences was significantly lower when compared to primary R1H tumors. In primary tumors a median pO(2) of 17 +/- 7 mmHg was measured. By contrast, the median pO(2) in R1H recurrences was only 5 +/- 5 mmHg (p0.05). The high frequency of pO(2) values5 mmHg indicated that R1H recurrences were significantly more hypoxic (58 +/- 5%) in comparison to primary tumors (22 +/- 4%). The histological sections of the R1H recurrences showed a higher heterogeneity in their tissue structure than primary nonirradiated tumors. The morphometric studies demonstrated a reduced microvessel density (91 +/- 21/9.04 mm(2) in the tumor periphery; p = 0.0001) compared with recurrent tumors (68 +/- 26) and an enhanced mean distance of tumor blood vessels, especially in the center of the R1H recurrences (184 +/- 20 vs. 243 +/- 70 mm; p = 0.0001).In R1H rhabdomyosarcomas tumor oxygenation in recurrent tumors following radiation therapy is significantly lower than in primary tumors. This observation has to be taken into account in cases of tumor recurrences where repeated radiotherapy, chemotherapy or combined treatment modalities are used.

To examine the influence of the hemorrheologic agent pentoxifylline (PTX) on tumor oxygenation and radiosensitivity.Tumor oxygenation in rat rhabdomyosarcomas R1H after PTX administration (50 mg/kg body weight) was measured using interstitial pO(2) probes (Licox CMP system and Eppendorf pO(2)-Histograph). Tumors were irradiated with (60)Co gamma-irradiation using single doses (15 and 30 Gy), conventional fractionation (60 Gy/30 fractions/6 weeks), and continuous hyperfractionation (54 Gy/36 fractions/18 days) in combination with PTX or an equivalent volume of physiological saline. Radiation effects were determined by tumor growth delay (2V(o)), and by partial and complete tumor remission.PTX increased tumor oxygenation for up to 45 min after administration of the drug. Single doses of 15 and 30 Gy of irradiation, when combined with PTX, produced little radiosensitization of the R1H tumors as indicated by dose-modifying factors (DMFs) of 1.11 and 1.04, respectively. In conventional fractionated irradiation with PTX, a DMF of 1.10 was obtained only. However, in continuous hyperfractionated irradiation with 18 x 50 mg/kg of PTX, the DMF with respect to tumor growth delay was found to be 1.37. Local tumor control was not influenced by PTX. In vitro studies identified R1H cells as p53 wildtype and showed a G1 arrest in response to irradiation. When 2 mM PTX was given prior to irradiation, it did not improve radiosensitivity of R1H cells as measured by clonogenic survival assays.PTX effectively enhances tumor oxygenation and radiosensitivity of R1H rhabdomyosarcomas, especially during continuous hyperfractionated irradiation. Given to rats as an adjuvant to fractionated irradiation, PTX does not enhance acute or late skin reactions or tumor metastasis. No radiosensitization was observed in vitro, when oxygen was not limiting. The observed radiosensitization by PTX is caused mainly by improved tumor oxygenation.

Background: Previous studies have reported synergistic effects of combined hyperthermia and chemotherapy and/or irradiation. The discussed underlying mechanism for this effect is an synergistic cytotoxic and radiosensitizing effect of hyperthermia. In addition, tumor blood-flow and, consequently, tumor oxygenation are increased during hyperthermia. Tumor response to irradiation and chemotherapy of well-oxygenated and vascularized tumors, in general, is superior to that of hypoxic tumors. Therefore, tumor oxygenation is recognized as an important predictive factor in the therapy of malignant tumors. Technically, the head-neck area remains outside the hyperthermia chamber during whole-body hyperthermia (WBH) as currently applied in a number of cancer treatment regimens. The aim of this therapeutic approach was to evaluate whether the blood flow during WBH also increased in the head-neck region and, if so, whether tumor oxygenation increase accordingly. Methods: A 60-year-old male Caucasian patient, with the original diagnosis of pT3 pN2b M0 squamous cell carcinoma of the oral cavity, who had undergone primary surgery and irradiation (total dose 60 Gy), developed three local recurrences with consecutive surgical resection, presenting now with another recurrent local tumor (histologically confirmed) without surgical or radiotherapeutical options due to lymphangiosis carcinomatosa. WBH was applied under full anaesthesia, using a humidified radiant heat device (Enthermics Medical Systems RHS-7500) in combination with synchronous application of chemotherapy (ifosfamide and carboplatin). Four cycles of this combined treatment (one cycle per month) were given. Tumor oxygenation and temperature were continuously monitored by Licox catheters by means of one point measurement during each treatment (3.5 h). Results: With a latency of 10 min, the increase of intratumoral temperature in the oral cavity was comparable to reference values in the esophagous. Maximum intratumoral temperature (oral cavity) was 41.8 °C (F). The average increase of tumor oxygenation was more than 100% in each individual cycle. Clinically, a partial tumor response was observed. Conclusions: During combined WBH and polychemotherapy, oxygenation is also significantly improved in a tumor in the head and neck area despite the fact that head and neck area remains outside the hyperthermia chamber during WBH. Intratumoral temperatures achieved are comparable to esophageal and rectal temperatures obtained during WBH.

Background: Surgical therapy of lymph node metastasis is based on accessibility for en bloc resection. First described as “radical neck dissection”, this original approach has since undergone various modifications. This has produced controversy about the particular indications for the individual techniques. The aim of this study was to evaluate whether intraoperative macroscopic inspection of the sternocleidomastoid muscle (SCM) in regard to tumor infiltration is sufficient to decide about muscle resection and whether there are prognostic differences between patients undergoing radical-versus modified radical (selective) neck dissection. Materials and methods: In a retrospective study, data on the surgical treatment of cervical lymph nodes and survival rates from 438 patients with head and neck malignancies managed in our department between 1988 and 1994 were analyzed in 1994 and again in 1999. Results: 337 patients (76.9%) underwent unilateral or bilateral selective neck dissection. In 101 patients (23.1%) a radical neck dissection was performed and the SCM was completely resected. Analysis of these cases showed intraoperative macroscopic tumor invasion of the SCM in 12 patients (11.9%), which could be confirmed histologically. In the remaining 89 cases (88.1%), a macroscopically intact muscle was resected; in none of these cases did histopathological examination show tumor infiltration of the SCM. Analysis of radically or selectively neck dissected stage III or IV patients with oral cavity, oropharyngeal, hypopharyngeal or laryngeal carcinomas did not show statistical differences in 2-, 5- and 10-year survival (54.8%, 23.7%, 18.7% versus 62.6%, 25.6%, 21.8%, respectively). Conclusions: (1) Intraoperative inspection of the SCM constitutes a valid parameter for deciding whether tumor infiltration is present or not. (2) There were no prognostic differences (2-year, 5-year and 10-year-survival) between stage III and IV patients with oral cavity, oropharyngeal, hypopharyngeal and laryngeal carcinomas treated by either radical or selective neck dissection.

Objectives/hypothesis: Nonpurulent rhinosinusitis can be treated successfully with cineole. Study design: Prospective, randomized, double-blinded, placebo-controlled study. Methods: We compared efficacy and safety of cineole capsules with placebo capsules in 152 patients with acute rhinosinusitis (76 patients in each treatment group). The dosage of the active ingredient was two 100-mg capsules of cineole three times daily. The primary end point was the reduction of a defined symptoms-sum-score based on symptoms and signs comparing baseline therapy difference from the beginning to the end of the 7-day treatment. Results: All randomly selected patients were assigned to the intention-to-treat-population. At the beginning, the mean symptoms-sum-score was 15.6 in both treatment groups. The mean values for the symptoms-sum-scores in the cineole group were 6.9 +/- 2.9 after 4 days and 3.0 +/- 2.8 after 7 days, and in the placebo group, 12.2 +/- 2.5 after 4 days and 9.2 +/- 3.0 after 7 days. The differences between both groups were clinically relevant and statistically significant after 4 and 7 days. The result for the primary end point was validated by the amelioration of the following secondary end points: headache on bending, frontal headache, sensitivity of pressure points of trigeminal nerve, impairment of general condition, nasal obstruction, and rhinological secretion. Mild side effects, possibly associated with medication, were observed in two patients as heartburn and exanthema after treatment with cineole. Conclusion: In patients with acute nonpurulent rhinosinusitis, timely treatment with cineole is effective and safe before antibiotics are indicated.

The purpose of this study was to evaluate the radioprotective potential of amifostine on the salivary glands of rats with respect to the acute and late effects. The head and neck area of WAG/RijH rats was irradiated with (60)Co-gamma rays (60 Gy/30f for 6 weeks). Amifostine (250 mg/m(2) body surface) or an equal volume of physiologic saline was applied intravenously 15 min before each irradiation. In the course of treatment the salivary glands were examined histopathologically. Body weight was measured sequentially during irradiation. A cytoprotective effect of amifostine on the acute toxicity of salivary glands could not be detected under fractionated irradiation. However, late effects such as fibrosis and necrosis of the glands 6 months after irradiation were less developed in the amifostine group. The weight loss of the amifostine-treated animals during fractioned irradiation was higher than in the irradiated group. Amifostine has a significant cytoprotective effect on the late toxicity of irradiated salivary glands. However, the acute toxicity of the glands during radiotherapy cannot be reduced.

Purpose: The “crowncork tympanoplasty” is a technique for the total reconstruction of the tympanic membrane. It is recommended in cases of ear malformation, blunting phenomena, and total deficiency of the membrane caused by chronic otitis media. Patients and Methods: The records of 12 patients undergoing “crowncork tympanoplasty” were reviewed. This includes 5 patients who were operated on because of middle ear malformation, 6 cases with a blunting phenomena following prior tympanoplasty, and 1 patient with chronic otitis media. Results: In each case an intact tympanic membrane was achieved. The air bone was reduced to 17, 19, 16, and 11 dB in the frequency 500, 1,000, 2,000, and 4,000 Hz. Conclusion: The use of cartilage for tympanoplasty has been useful despite the comparatively worse vibration characteristics of the rigid material. Total reconstruction of selected problem cases using this “crowncork technique” has resulted in good healing with favorable hearing results and should be incorporated into the routine of the skilled otosurgeon.

Objective: To determine the safety and efficacy of targeted antitumor therapy with cisplatin/epinephrine injectable gel in patients with advanced squamous cell carcinoma of the head and neck. Design: Two prospective, double-blind, placebo-controlled phase III trials of identical design. Crossover from blinded to open-label phase was permitted for patients with disease progression. Setting: Tertiary referral centers in North America and Europe. Patients: One hundred seventy-nine intensively pretreated patients with recurrent or refractory squamous cell carcinoma of the head and neck. Intervention: Cisplatin/epinephrine injectable or placebo gel was administered by direct intratumoral injection; up to 6 weekly treatments. Dose was 0.25 mL of active or placebo gel per cubic centimeter of tumor up to 10 mL total. Patient benefit after local tumor control of the most symptomatic tumor was assessed by patients and physicians using the Treatment Goals Questionnaire. Main Outcome Measures: Local tumor response and patient benefit attributable to improvements in tumor-related symptoms. Results: Combined results for the 178 patients with evaluable data in the 2 trials confirmed objective tumor responses in 35 (29%) of 119 patients, including 23 (19%) complete responses achieved with cisplatin/epinephrine gel, vs 1 (2%) of 59 for placebo (P