High-dose rate intracavitary radiation therapy for advanced head and neck tumors

Fifty-seven treatments were performed on 27 head and neck pateints with recurrent or residual tumors on a high dose rate, remote controlled afterloading unit: There were 16 cases of maxillary sinus tumors, 6 epipharynx, 3 alveolar ridge, 1 hard palate and 1 floor of mouth. All patients have been followed up more than 2 years except one. Five patients are alive without local recurrence for more than 2 years. In 13 patients local tumors disappeared once and normal mucosa covered the tumor sites. Two patients died from local bleeding. In six patients this method failed to destroy tumors. Our prupose was palliative local control: therefore, in two-thirds of cases treated we were successful with this easy method of nonfractionated acute intracavitary radiation. This result is favorable, considering that all cases treated here were failures following full dose external radiation, although the treatment had to be repeated more than twice in 15 cases. Relief of symptoms is excellent when this therapy is used.     

Oxygenation of head and neck tumors

BACKGROUND: Tumor hypoxia could play a role in the response to radiation therapy. Few data are available on oxygen tension (pO2) measurements in head and neck tumors. METHODS: The KIMOC-6650 Histograph (Eppendorf, Hamburg, Germany) was used to measure the oxygenation status of normal tissues and head and neck tumors in 20 patients. RESULTS: The median pO2 for normal tissues was 43 mmHg with very low pO2 values (2.0 mmHg or less) recorded in two patients. Low median pO2 levels (10 mmHg or less) were recorded in 2 of 5 primary tumors and in 11 of 15 metastatic lymphadenopathies, with very low values in 11 nodes. The median pO2 in tumors was lower than that of normal tissues in 12 of 15 patients with comparative measurements. Oxygen tension was recorded in three nodes after an evaluation of tissue density (by computed tomographic scanner); in two nodes, the mean and median pO2 values were lower in the hypodense areas than in isodense areas. The data for N2 and N3 nodes showed significantly more values below 2.0 mmHg as nodal size increased (P < 10(-4), by chi-square test). No systematic decrease in pO2 was recorded from the periphery to the center of the tumors. CONCLUSIONS: Very low pO2 values, corresponding to radiobiologic hypoxia, were found in most of these tumors. The prognostic value of these pO2 measurements in regard to treatment response remains to be demonstrated.     

Salivary gland tumors after childhood radiation treatment for benign conditions of the head and neck: dose-response relationships

In this study the mechanisms were investigated whereby ACE-inhibitors improve pulmonary diffusion for carbon monoxide (DLco) in chronic heart failure. The two subcomponents of DLco are the alveolar-capillary membrane conductance (DM) and the capillary blood volume (VC). Stress failure of the membrane in chronic heart failure provides a mechanism for reduction of DM and, as a consequence, impairment of DLco. In 27 patients with chronic heart failure in NYHA functional class II to III and in 13 age- and sex-matched normal subjects, we evaluated the pulmonary function and determined DM and VC, according to the classic Roughton and Forster method, while they were given placebo, at 48 hours and 8 weeks after starting enalapril treatment (10 mg bid). ACE-inhibition had no effect in controls at both short- and mid-term. In chronic heart failure patients, a reduction in VC (likely consequence of a decrease in capillary pulmonary pressure) was the only change observed at 48 hours. At 8 weeks, DM was greatly increased even when the effective alveolar volume (VA) was accounted for (DM/VA), resulting in a significant improvement in DLco, despite a decrease in VC. The slow onset DM improvement makes it likely that the modulatory effect of ACE-inhibition on the membrane function emerges gradually, suggesting that it is likely dissociated from changes in pulmonary capillary pressure and VC. Thus, derangements of the alveolar-capillary membrane in chronic heart failure increase gas diffusion resistance; ACE-inhibition restores the diffusive properties of the membrane and gas transfer, and protects the lung when the heart is failing.     

Carotid artery stenosis in patients who have undergone radiation therapy for head and neck malignancy

Although it is established that small and medium sized arteries undergo extensive radiation damage, the effect on large vessels such as the carotid arteries is less well understood. We sought to determine if an increased severity of carotid artery stenosis is present in patients who have undergone radiotherapy for head and neck tumours. 45 patients aged 43-90 years (average 67) with head and neck malignancies treated with radiotherapy underwent colour Doppler ultrasonographic scanning of the carotid arteries. These patients were compared with a population of asymptomatic historical controls. 60% of patients demonstrated stenosis ranging from 21 to 86%. 38% of patients demonstrated a stenosis greater than or equal to 50%. Carotid artery stenosis appears to be increased in patients who have previously undergone treatment with radiotherapy to the head and neck regions compared with controls (p < 0.001). These findings suggest that radiation has an adverse effect on large vessels. Colour Doppler follow-up may be indicated for patients receiving head and neck radiation therapy.     

Amifostine: a radioprotector in locally advanced head and neck tumors

Patients with locally advanced head and neck tumors were treated +/-amifostine (200 mg/m2, i.v.) before radiotherapy (5x 2 Gy, for 6 weeks). A significant decrease in side effects (p=0.034) using the oral assessment score and duration of mucositis (p=0.02) in the amifostine group was observed. Amifostine is feasible and effective, decreasing acute and late side effects in patients with head and neck tumors.     

The time span between symptom onset and starting treatment in head and neck tumors

The interval between the onset of symptoms in patients with head and neck cancers and the introduction of treatment was evaluated. During a 1-year period, patients were interviewed to determine the duration of any delays from the onset of complaints until the first visit to a doctor. Also asked was how long it took to be referred to an ENT specialist and actual referral to our department. We then determined the interval from diagnosis to the introduction of therapy. It was found that the delay of patients who went directly to an otorhino-laryngologist was shorter (median, 8 weeks) than that of patients who first went to their family doctors (median, 13 weeks) (P < 0.02). The latter then took an additional 4 weeks before sending patients to an otorhinolaryngologist. Referral from the ENT specialist to our department took another 2 weeks, as well as our staging and pre-therapeutic management. Our findings show that the patient himself is the critical factor in delaying diagnosis and therapy. Tumor patients with greater professional qualification went to their doctors earlier (P < 0.0001) or more often went directly to an ENT specialist (P < 0.002). Consultations of physicians without experience in otorhinolaryngology caused yet further delays.     

Recent trend in the study of head and neck tumors

Episcleral venous pressure was measured by means of an air jet at different levels of occlusion of the measured vessel. This was repeated at different points in one branching venous plexus system. The results indicate that the most reliable estimate of the pressure is obtained at the pressure level at which the blood column becomes somewhat paler. Occlusion of the vessel causes a rise in venous pressure which may be considerable, especially in large veins.     

An improved quality of life self-questionnaires specific for head and neck tumors

The effects of human and porcine insulins on the symptomatic, physiological, and counterregulatory hormonal responses to acute hypoglycaemia were compared in 40 patients with Type 1 diabetes, 20 of whom were newly diagnosed while 20 had been treated for between 5 and 20 years. In a double-blind, cross-over trial all patients were treated with human or porcine insulin, in random order, for two consecutive 3-month periods. At the end of each treatment period they were subjected to an acute episode of experimental hypoglycaemia induced by a continuous intravenous infusion (2.0 mU kg(-1)min(-1)) of the same insulin species. Haemodynamic, sweating, and tremor responses were measured during both studies, symptom scores were recorded and the arterialized plasma glucose thresholds for autonomic activation and the onset of subjective symptoms were identified. In all patients the glycaemic thresholds for the initiation of the autonomic physiological responses to hypoglycaemia and the onset of the symptomatic response were concurrent and did not differ with insulin species (plasma glucose 1.94 vs 1.96 mmol I(-1), human vs porcine studies). The onset, temporal pattern, nature, and magnitude of the physiological responses (sweating, heart rate, blood pressure, and tremor) during acute experimental hypoglycaemia were also identical with each insulin species. The magnitude and temporal pattern of the response of counterregulatory hormones (adrenaline, noradrenaline, glucagon, ACTH, and GH) to hypoglycaemia as induced by human and porcine insulins were indistinguishable, as were the total and individual scores of autonomic and neuroglycopenic symptoms. In conclusion, in patients who had newly diagnosed and intermediate duration (5-20 years) of diabetes, the symptomatic, physiological, and counterregulatory hormonal responses to acute insulin-induced hypoglycaemia did not differ between human and porcine insulins, and the plasma glucose thresholds at which the symptomatic and autonomic responses were initiated were identical with both insulin species. This study does not support the hypothesis that treatment with human insulin modifies the symptomatic, physiological, and counterregulatory hormonal responses to acute hypoglycaemia.     

Implant reconstruction following removal of tumors of the head and neck

Functional maxillofacial rehabilitation following tumor ablation depends on many variables. These include the magnitude of hard or soft tissue defects, the use of adjunctive chemotherapy or radiation therapy, and the presence of underlying systemic disease. The physiologic effects of tumor ablation and radiation therapy on local tissues and grafted bone are discussed in this article in relation to the ultimate use of implant supported prostheses. Cases are presented to illustrate a variety of clinical situations.     

Recent treatment modality for advanced head and neck carcinomas

We have previously shown that fibronectin-binding protein I (SfbI) of Streptococcus pyogenes can act as an adjuvant for mucosal-delivered antigens (Medina, E., Talay, S. R., Chhatwal, G. S. and Guzmán, C. A. 1998. Eur. J. Immunol. 28:1069). To characterize the underlying mechanism of the adjuvancity, we investigated the in vitro stimulating activity of SfbI. The SfbI protein promoted a dose-dependent proliferation of mouse spleen cells. Studies performed using cellular subpopulations showed that proliferation involved B cells and was T cell- and macrophage-independent. SfbI also induced lg production by B cells in a T cell-independent manner. The kinetics of lg isotype accumulation in supernatant fluids and the analysis of Ig-secreting cells suggested that SfbI stimulates B cells expressing different Ig isotypes rather than promoting the isotype switching of single subpopulations. Experiments performed with recombinant proteins encompassing different functional domains of SfbI showed that the fibronectin-binding repeats were responsible for B cell activation. The sera from mice immunized by the intranasal route with SfbI did not react with either double-stranded DNA, cardiolipin or collagen. Interestingly, stimulation with Sfbl also resulted in the up-regulation of MHC class 11 molecules expression by B cells and macrophages. The elucidation of the underlying molecular events to the immunomodulatory effect exerted by SfbI will facilitate the exploitation of the potential of this molecule for the generation of mucosal vaccines.     

Primary and secondary pulmonary tumors associated with head and neck carcinoma

The authors analyze personal and literature results in surgery of primary and secondary lung cancer associated with head and neck malignancies. Eighteen patients with primary lung cancer associated with head and neck cancer were compared with six patients affected by pulmonary metastases from head and neck cancer. In the first group the 3-year postoperative survival rate was 60.5%, in the second group 33%. Differential diagnosis between primary and metastatic lung tumours may be easy when multiple pulmonary nodes are present. When only one pulmonary node is present, diagnosis is more difficult. Thoracotomy is necessary to perform the correct diagnosis and the best postoperative medical treatment.     

Intra-arterial infusion chemotherapy for recurrent breast cancer via an implantable system--the second report

Intra-arterial infusion chemotherapy via an implantable port catheter has been applied in 16 patients with locally recurrent breast cancer. The regimen consisted of induction and subsequent maintenance: intra-arterial infusion of epirubicin (EPI). Non-responders were entered into the second-line regimen consisting of Methotrexate and 5-FU (MF). The results were as follows: 1) The response rate (CR+PR) of EPI to locoregional lesions was 50%, and the median duration of response was 5.7 months. 2) The response rate and the duration of response of MF were 25% and 3 months, respectively. 3) Patients with ER-rith, no previous therapy and a long disease-free interval tended to have a high rate of response to intra-arterial infusion therapy. 4) Improvements of QOL, such as intractable pain, infection and severe lymphedema were recognized in 68.6% of the cases. In more than half of the cases, these treatments were carried out in an outpatient clinic. 5) Leucopenia and catheter or portal problems were encountered in 68.6% and 25.0%, respectively. We conclude that intra-arterial infusion chemotherapy via implantable system is a promising modality with regard to therapeutic effect and improvement of quality of life.     

Continuous intrathecal meperidine via an implantable infusion pump for chronic, nonmalignant pain

OBJECTIVE: To report a continuous infusion of intrathecal meperidine via an implanted infusion pump for nonmalignant, chronic pain. CASE SUMMARY: A 69-year-old white woman had chronic, nonmalignant low-back pain and bilateral leg pain. Multiple drug therapies and other interventional techniques had failed. The patient achieved significant pain relief by a continuous infusion of intrathecal meperidine via an implanted infusion pump. DISCUSSION: To our knowledge, this is the first report of meperidine administered intrathecally by continuous infusion. Continuous infusion of intrathecal and epidural opiates by implanted infusion pumps is becoming more widely recognized as an alternative treatment for patients with chronic, benign pain. Epidural and intrathecal meperidine is an effective analgesic for short-term surgical procedures. Data reporting effective relief and safety with continuous intrathecal meperidine remain limited. CONCLUSIONS: Continuous intrathecal meperidine via an implantable infusion pump may be an effective alternative in the treatment of chronic pain.     

Continuous infusion etoposide/carboplatin for treatment of refractory acute leukemia

Etoposide (125 mg/m2/d) and carboplatin (200 mg/m2/d) were administered by continuous 5-day intravenous infusion to 10 patients with relapsed or refractory acute leukemia (7 ANLL, 1 ALL, 2 blast crisis of CGL). No complete or partial response was observed despite dose-limiting toxicity characterized by severe diarrhea in four patients and neutropenic colitis in two additional cases. We cannot recommend the present schedule of drug administration for the treatment of acute leukemia.     

Complicating mucosal reactions in patients receiving radiation therapy for head and neck cancer

Radiation mucositis is characterized by erythema, pseudomembranes, and ulceration of mucosa in the irradiated field. We present two cases of oral mucosal changes in patients treated with radiotherapy in the head and neck region, which included mucosal erythema and ulceration outside of the radiated fields. One case was confirmed as herpes virus infection, and the other was diagnosed as Sweet's syndrome. When mucositis extends beyond the radiation fields, the clinician should consider other causes of mucosal inflammation and erythema in order to begin appropriate management.