Clinical characteristics and diagnostic delay of head and neck cancer: results from a prospective study in Belgium

A prospective study of head and neck cancer patients was started to gather information about topographic and clinical characteristics of head and neck cancer, alcohol and nicotine abuse and the delay in diagnosis. More than half of the patients consulted our institution with an advanced stage of disease. As was expected, we found a positive association between the size of the tumour and the clinical stage of the neck. Concerning nicotine and alcohol abuse, our results support the hypothesis that tobacco smoking is more strongly associated with lesions in sites heavily exposed to inhaled smoke, whereas alcohol consumption has a stronger effect on structures belonging to the 'food channel' and reservoir systems. We found no association between delay and tumour stage at diagnosis, but a statistically significant correlation was found between the delay and the tumour site. This leads us to conclude that the tumour stage is determined mostly by the biology of the tumour.     

Head and neck cancer: guidelines for chemotherapy

Head and neck cancer is estimated to be one of the most prevalent cancers in the world. This tumour type accounts for 5% of all new cancer cases in the US and Europe each year. Patients with locally recurrent or metastatic squamous cell carcinoma of the head and neck have a poor prognosis, with a median duration of survival between 4 and 6 months. During the past few years, screening for potentially active new compounds, new associations and new modalities of chemotherapy administration have had some degree of success. Clinical investigations have also focused on the addition of chemotherapy to locoregional treatment for patients with locally advanced disease. Induction chemotherapy or concomitant chemo- and radiation therapy can result in high response rates, and reduced incidence of distant metastases. However, there is no clear demonstration of any benefit from the addition of chemotherapy to locoregional therapy on overall survival in patients with resectable disease. In patients with resectable laryngeal or hypopharyngeal cancer, chemotherapy combined with radiotherapy can be considered as a standard treatment option for larynx preservation, keeping total laryngectomy reserved for salvage therapy. In patients with unresectable head and neck cancer, simultaneous chemoradiotherapy has been shown to improve locoregional control and survival, at the cost of greater toxicity. Outside clinical trials, this approach can also be considered as a standard therapy for unresectable disease.     

Refractory head and neck pain. A difficult problem and a new alternative therapy

Mitral valve repair was performed in six patients by transferring the posterior tricuspid leaflet with its sub-valvular apparatus onto the mitral valve. This new technique considers the tricuspid valve as the patients own tissue bank where the posterior leaflet and eventually the adjacent part of the anterior leaflet is used as a "donor" valve, based on the knowledge that the right atrio-ventricular valve can be efficiently repaired with a very low risk of significant dysfunction. The mitral repair consists of incorporating the tricuspid autograft by securing the tricuspid papillary muscle to the mitral papillary muscle and by suturing the leaflet tissue where required. A mitral annuloplasty ring reinforces the repair. The tricuspid valve is subsequently repaired by annular plication and leaflet suture. A tricuspid ring is necessary to maintain efficient remodeling. The six patients ages ranged from 20 to 70 years. A etiology, was rheumatic in the first case and degenerative in the following. In three cases, sterilised endocarditis was responsible for ruptured chordae and leaflet destruction. The mitral insufficiency was located in a commissural area in 4 cases, and was due to a widespread posterior prolapse in 2. Post-operative control transesophageal echocardiography confirmed the excellent results of the repair and proved that, in selected cases, the tricuspid leaflet inserted onto the mitral apparatus is very efficient in correcting mitral insufficiency, without causing significant tricuspid impairment. With a 3 to 7 month follow-up, the results are stable.     

Anemia is associated with lower local-regional control and survival after radiation therapy for head and neck cancer: a prospective study

PURPOSE: To evaluate the prognostic value of anemia in squamous cell carcinomas in the head and neck treated with curative radiation therapy alone. MATERIALS AND METHODS: In a prospective study, the hemoglobin level was measured prior to radiation therapy in 217 patients (188 [87%] men and 29 [13%] women) with cancer of the oral cavity (n = 61 [28%]), oropharynx (n = 53 [24%]), hypopharynx (n = 21 [10%]), and larynx (n = 82 [38%]). Anemia, defined as hemoglobin level below 13.5 g/dL in men and below 12.0 g/dL in women, was diagnosed in 58 (31%) of the men and five (17%) of the women. Median follow-up was 29 months (range, 2-63 months). RESULTS: The 2-year actuarial probability of local-regional control was 69% (95% confidence interval, 63%, 76%). Multivariate analysis showed the relative risk of failure of local-regional control to increase for stage T3 and T4 tumors (1.8 [95% confidence interval, 1.1, 3.1]), stage N3 nodes (3.6 [95% confidence interval, 1.8, 7.1]), weight loss (2.2 [95% confidence interval, 1.3, 4.0]), and anemia (1.6 [95% confidence interval, 1.0-2.7]). The relative risk of death increased for stage T3 and T4 tumors (2.5 [95% confidence interval, 1.4, 4.3]), N3 nodes (4.0 [95% confidence interval, 1.0, 7.9]), oral cavity tumors (2.0 [95% confidence interval, 1.2, 3.2]), male sex (4.1 [95% confidence interval, 1.3, 13.1]), weight loss (2.2 [95% confidence interval, 1.3, 3.7]), and anemia (1.7 [95% confidence interval, 1.03, 2.7]). CONCLUSION: Moderate anemia appeared to be an independent prognostic factor in squamous cell carcinoma of the head and neck treated with radiation therapy alone.     

Immunotherapy of head and neck cancer

Understanding the mechanisms responsible for photodamage to the skin is most important for dermatology. 3-D cultures have been used as tools to mimic the in vivo situation for several years. We irradiated such a system containing human dermal fibroblasts cultured in collagen gels, a well-known model considered to be a dermal equivalent, which reproduces the interaction between cells and the surrounding extracellular matrix. The effects of solar irradiation (315-800 nm) on the steady-state levels of the mRNAs of extracellular matrix components (type I and III collagens) and their degrading enzymes (interstitial collagenase, MMP-1 and stromelysin 1, MMP-3) were measured. Exposure to low levels of solar radiation (0-10 J cm-2 in the UVA, i.e. suberythemal UVA doses) caused a transient decrease in type I procollagen mRNA, an increase in MMP-mRNA, and no change in type III procollagen mRNA steady-state levels. These results describe the early changes in the connective tissue of the skin following exposure to low-level solar stimulation, and may help explain the long-term changes in photodamaged skin.     

Symptom management for incurable head and neck cancer

The overall cure rate for cancer of the head and neck is about 50%. For those patients who will die of their disease, active palliative care is needed. This article seeks to present a practical approach to managing the symptoms, especially pain, suffered by patients with incurable malignancy. (See related article, Using Opioids to Control Suffering: A Painstaking Approach, on page 20 of the February, 1997 WMJ.) While the focus is on head and neck cancer, the principles and much of the information contained herein is applicable to patients dying from other types of malignant disease.     

Chemoprevention of head and neck cancer

The role of pituitary adenylate cyclase-activating polypeptide (PACAP) in the regulation of exocrine and endocrine pancreas was investigated in conscious sheep. Intravenous infusions of PACAP-27 and PACAP-38 (1, 3, and 10 pmol/kg/min) for 10 min during phase II of the duodenal migrating myoelectric complex accelerated pancreatic protein and amylase outputs dose-dependently. The responses in enzyme secretion to both PACAPs at the highest doses were inhibited significantly by atropine infusion (14.4 nmol/kg/min). Vasoactive intestinal polypeptide (VIP) at 3 pmol/kg/min significantly accelerated protein but not amylase outputs, although the response to the highest dose was not significantly influenced by atropine. PACAP-27 and VIP increased pancreatic juice flow and bicarbonate output dose-dependently; however, the responses to the highest dose were not altered significantly by atropine. On the other hand, intravenous injection of PACAP-38 (100 pmol/kg) did not influence basal plasma concentration of insulin, glucagon, and glucose. Moreover, PACAP-38 (1-100 pmol/kg) altered neither pancreatic endocrine response to intravenous infusion of glucose (20 mumol/kg/min) not that to n-butyric acid (33 mumol/kg/min). These results suggest that PACAP contributes to the regulation of exocrine secretion of the ovine pancreas but not to endocrine secretion. PACAP appears to accelerate pancreatic enzyme secretion mostly via the cholinergic nerves.     

Sexuality in head and neck cancer patients

We describe a patient with Hirschsprung disease and autism. High-resolution karyotyping indicated that the patient has an interstitial deletion of 20p11.22-p11.23. Microsatellite analysis showed a deletion involving a 5-6 cM region from the maternally derived chromosome 20. The deleted region is proximal to, and does not overlap, the recently characterized Alagille syndrome region. This region of 20p has not yet been implicated in Hirschsprung disease or autism. However, this region contains several genes that could plausibly contribute to any phenotype that includes abnormal neural development.     

Moderate-dose methotrexate in head and neck cancer

200 mg/m2 methotrexate given intravenously in a running drip for 6 h has been used as an initial adjuvant therapy in 38 patients with advanced head and neck cancer. The response rate is as high as 80%, with 21% achieving complete remission. Histologically, specimens were tumor free in 3 patients. Toxicity in 38 patients included leukopenia (4), mucositis (6) and diarrhea (1). This particular dose of methotrexate appears to be safe and usually does not need leucovorin rescue. Also, when given as initial treatment, it is effective in reduction of tumor bulk. A prolonged randomized trial is essential to determine its role in improving long-term survival.     

Opioid therapy for chronic noncancer back pain. A randomized prospective study

STUDY DESIGN: A randomized, open, long-term, repeated-dose comparison of an anti-inflammatory drug and two opioid regimens in 36 patients with back pain. OBJECTIVES: To examine the long-term safety and efficacy of chronic opioid therapy in a randomized trial of patients with back pain. METHODS: All participants underwent a 4-week washout period of no opioid medication before being randomly assigned to one of three treatment regimens for 16 weeks: 1) naproxen only, 2) set-dose oxycodone, or 3) titrated-dose oxycodone and sustained-release morphine sulfate. All patients then were assigned to a titrated dose of opioids for 16 weeks and then gradually tapered off their medication for 12 weeks. Finally, all participants were monitored for a 1-month posttreatment washout period. Each patient was called once a week for a report on pain, activity, mood, medication, hours awake, and adverse effects and was monitored carefully for signs of abuse and noncompliance. RESULTS: Weekly reports during the experimental phase showed the titrated-dose group to have less pain (P < 0.001) and less emotional distress (P < 0.001) than the other two groups. Both opioid groups were significantly different from the naproxen-only group. During the titration phase, patients also reported significantly less pain and improved mood. Few differences were found in activity or hours asleep, or between average pretreatment and posttreatment phone-interview and questionnaire variables. No adverse events occurred, and only one participant showed signs of abuse behavior. CONCLUSIONS: The results suggest that opioid therapy has a positive effect on pain and mood but little effect on activity and sleep. Opioid therapy for chronic back pain was used without significant risk of abuse. However, tapered-off opioid treatment is palliative and without long-term benefit.     

FDG PET in head and neck cancer

In our extensive experience with FDG PET imaging in head and neck cancer, we have found the technique to be of high accuracy but of limited usefulness. This seeming paradox arises from several causes. Competing techniques such as CT, MR imaging, and even clinical examination already have good accuracy. In addition, high-resolution studies such as CT and MR imaging provide information required for treatment planning that is unavailable from FDG PET images. The high cost of FDG PET militates against its use in this setting, in which only a small marginal gain can be expected. In the special problem areas in which FDG PET might be expected to offer unique advantages, such as screening for second primary lesions, searching for unknown primary lesions, or differentiating benign salivary rumors from malignant lesions, the results of FDG PET have been disappointedly poor. Of these special problem areas, only the question of accuracy in finding occult primary lesions appears unresolved and in need of further study. The single application in which FDG PET appears to be advantageous is the posttherapy setting. In this setting, the technique is definitely superior to alternative methods of determining tumor recurrence and differentiating posttherapy sequelae such as radiation necrosis from tumor recurrence. We believe that considerable opportunity remains for further research on the use of FDG PET in head and neck cancer. Other agents such as 11C-methionine for example, might improve the diagnostic accuracy of FDG PET in some of the problem areas that we have identified, such as the early postirradiation period. We currently have such a study under way. Also, because FDG PET offers a unique way to measure tumor metabolism, further investigation of the use of FDG PET tracers to evaluate various biologic parameters such as proliferation rates or tumor hypoxia are needed. Such studies could provide a noninvasive technique to identify which fractionation schemes or combinations of therapy might be useful for individual patients. A final caveat is in order. Although our findings of the usefulness (and lack thereof) of FDG PET in head and neck cancer may be disappointing to many, these results should not be generalized to other applications of FDG PET in oncology. Each tumor type and setting presents its own specific problems, and in some instances FDG PET offers unique advantages over other imaging techniques. A good example is the setting of primary lung cancer, in which FDG PET appears clearly superior to all other methods of pretherapy screening [19-20].     

Suicide in head and neck cancer patients

PURPOSE: It has been well documented that patients with a diagnosis of cancer are at an increased risk of committing suicide. However, there is a paucity of literature on the risk of suicide in the head and neck cancer patient. The purpose of this investigation was to determine the incidence of suicide and expressed suicidal intent in a series of such cancer patients. PATIENTS AND METHODS: A retrospective chart review of 241 patients who were diagnosed with head and neck cancer at the University of Maryland Oral and Maxillofacial Surgery Oncology Division was done. RESULTS: Three patients were identified who committed suicide, 1.2% of the series. Two patients expressed suicidal intent, and four patients refused all treatment and counseling, preferring to die of their disease. CONCLUSIONS: Head and neck cancer patients have many of the same risk factors for suicide as patients with other forms of cancer. To reduce this risk, it is essential that the surgeon maintain good rapport with the patient, because this serves as a foundation for all other aspects of their therapy. In addition, these patients need to be fully evaluated for depression, hopelessness, pain, and other factors important in raising the possibility of suicide, and appropriate, aggressive management must be provided.     

Somatization in cross-cultural perspective: a World Health Organization study in primary care

OBJECTIVE: The purpose of this study was to examine the phenomenon of somatization in different cultures by determining its frequency and correlates in primary care settings in 14 countries. METHOD: Consecutive primary care patients (N = 25,916) were screened with the 12-item General Health questionnaire, and a stratified sample (N = 5,438) was interviewed with the Composite International Diagnostic Interview. Interviewed patients were also assessed for physical disease burden, self-rated overall health, physician-rated physical health status, number of disability days, and interviewer-rated occupational role functioning. The authors determined center-specific associations with the use of logistic regression analyses in which confounding variables were controlled. RESULTS: ICD-10 defined somatization disorder was relatively uncommon in most primary care settings. A less restrictively defined form was more common. Symptom rates were much higher in South American sites. There was a modest association with low education. Otherwise, frequency of unexplained somatic symptoms did not clearly vary according to geography or level of economic development. Somatizing patients were at elevated risk for self-reported disease burden, negative perception of their health, and comorbid depression and generalized anxiety disorder. Somatization was also commonly associated with disability. Cultures did not differ markedly in the pattern of these associated features. CONCLUSION: Somatization is a common problem in primary care across cultures and is associated with significant problems and disability.     

Postoperative Tc-scintimetry in femoral neck fracture. A prospective study of 46 cases

This article presents panic diary results of a dose-response study with imipramine hydrochloride in panic disorder with agoraphobia patients. Analysis of variance revealed significant time effects on panic frequency and severity measures, but group x time interaction effects were present for the severity measures only. Results also provided evidence for a positive dose-response relationship with 20 percent of patients in the placebo group, 31 percent in the low-dose group (0.5 mg/kg/day), 54 percent in the medium-dose group (1.5 mg/kg/day), and 70 percent in the high-dose (3 mg/kg/day) group being free of recurrent or severe panic attacks at posttreatment. Further stratified and logistic regression analyses revealed a direct linear relationship between total plasma tricyclic concentration and response. These findings affirm the dose-dependent nature and the specificity of imipramine's antipanic effects.     

Skin cancer of the head and neck

The incidence of skin cancers is increasing at a rate greater than any other cancer occurring in humans. In this era of managed care, patients with a suspicious skin lesion may first present to their primary care physician for evaluation. Therefore, it is important for the primary care physician to be able to distinguish between benign and malignant pigmented lesions, to know how to evaluate such a patient, and to appreciate the importance of appropriate interdisciplinary management of these patients.     

Radiation therapy and concurrent cisplatin administration in locally advanced head and neck cancer. A Hellenic Co-operative Oncology Group study

In an attempt to improve local control of locally advanced head and neck cancer, radiation therapy was combined with cisplatin. Forty-eight patients entered into this study. All patients were irradiated with a 60Co unit and according to the protocol they should receive 70 Gy in the tumor area and 45 Gy in the rest of neck. Cisplatin was administered at a dose of 100 mg/m2 on days 2, 22 and 42. Thirty-seven (80%) patients received the total radiation dose as initially planned. Thirty-four (72%) patients achieved complete and 5 (10%) partial response. Grade 3-4 toxicities included vomiting (14%), stomatitis (4%), diarrhea (2%), myelotoxicity (14%), hoarseness (4%), dysphagia (30%), weight loss (32%), nephrotoxicity (4%) and dermatitis (2%). After a median follow-up of 26 (range, 18-33) months, 16 patients have died. Among the 35 complete responders 6 later on relapsed. Median relapse-free survival has not yet been reached. Combined radiation therapy and cisplatin appears to be a highly active treatment in patients with advanced head and neck cancer as far as primary locoregional response is concerned.