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.     

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.     

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.     

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.     

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.     

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.     

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.     

Intraoral reconstruction in head and neck cancer surgery

The effect of prostaglandins (PGs) on the hepatic biotransformation of hexobarbital (Hechi) and p-chloro-N-methylaniline (PCMA) was determined in male rats. PCMA metabolism in slices was decreased by all PGs (PGA1, PGB1, PGE1, PGE2, PGF1alpha, PGF2alpha), ranging in concentration from 1 mu M to 1 mM. PGA1, at 1 mM, produced the greatest degree of inhibition, 39%. PG addition to microsomes, however, failed to alter PCMA metabolism. In contrast to PCMA biotransformation, Hechi metabolism was increased by all PGs in slices but not in liver subfractions. PGs of the E and F series were the most potent, producing a two-fold increase in Hechi metabolism at 1 mM after a 20 min preincubation. The increased effect was observed as early as 10 min and lasted for 4 hr. The relationship of PG metabolism and binding to cytochrome P-450 is presented as a possible mechanism to account for the opposite effects on Hechi and PCMA, type I and II substrates respectively, metabolism.     

Subclavian pseudoaneurysm mimicking recurrent head and neck cancer

Vascular blowouts are devastating complications of head and neck oncologic surgery that are easily diagnosed with oropharyngeal or external bleeding. We present herein a case of a pseudoaneurysm of the subclavian artery that mimicked recurrent head and neck carcinoma. Vascular lesions arising in the base of the neck may present with few signs of vascular injury. Head and neck surgeons should be aware of this unusual complication to avoid a potentially life-threatening event. We report difficulties in diagnosing subclavian pseudoaneurysm, a review of the vascular injuries related to this condition, as well as approaches to bleeding at the base of the neck.     

The nature of the head and neck cancer

Squamous cell carcinoma of the head and neck is a disease predominantly of males and is due to a variety of known environmental irritants, notably cigarette smoke. Dietary, viral and immunological factors may also be relevant. Head and neck squamous cancers express epidermal growth factor receptors and some show weak levels of oestrogen receptor activity, but a reliable serum marker of tumour burden remains to be identified. The prognosis is found to be less favourable in females, in those with advanced T stage, in association with multiple node involvement, especially where extracapsular spread is present and where the T4/T8 ratio is elevated. Administration of heterologous blood during therapy may also have an adverse effect on prognosis. Interested clinicians must remember that most cases are preventable.     

Associations between physical activity and susceptibility to cancer: possible mechanisms

Physical activity is associated with a reduced risk of all-cause and colonic cancers, and it seems to exert a weaker effect on the risk of breast, lung and reproductive tract tumours. This review examines possible mechanisms behind the observed associations. Restriction of physical activity by pre-existing disease may contribute to the association with lung cancers, but seems a less likely explanation for other types of tumour. Indirect associations through activity-related differences in body build or susceptibility to trauma seem of minor importance. Potential dietary influences include overall energy balance and energy expenditure, the intake and/or bioavailability of minerals, antioxidant vitamins and fibre, and the relative proportions of protein and fat ingested. Links between regular exercise and other facets of lifestyle that influence cancer risks are not very strong, although endurance athletes are not usually smokers, and regular leisure activity is associated with a high socioeconomic status which tends to reduce exposure to airborne carcinogens, both at work and at home. Overall susceptibility to cancer shows a 'U'-shaped relationship to body mass index (mass/height2) reflecting, in part, the adverse influences of cigarette smoking and a tall body build for those with low body mass indices and, in part, the adverse effect of obesity at the opposite end of the body mass index distribution. Obesity seems a major component in the exercise-cancer relationship, with a particular influence on reproductive tract tumours; it alters the pathways of estradiol metabolism, decreases estradiol binding and facilitates the synthesis of estrogens. Among the hormonal influences on cancer risk, insulin-like growth factors promote tumour development and exercise-mediated increases in cortisol and prostaglandin levels may depress cellular components of immune function. However, the most important change is probably the suppression of the gonadotropic axis. Apparent gender differences in the benefits associated with regular exercise reflect gender differences in the hormonal milieu and also a failure to adapt activity questionnaires to traditional patterns of physical activity in females. The immune system is active at various stages of tumour initiation, growth and metastasis. However, acute and chronic changes in immune response induced by moderate exercise are rather small, and their practical importance remains debatable. At present, the oncologist is confronted by a plethora of interesting hypotheses, and further research is needed to decide which are of practical importance.     

Chemoprevention in head and neck cancer: basic science and clinical application

As cure rates in childhood acute lymphoblastic leukemia edge toward 80%, the focus of research is shifting to better means of identifying and treating resistant cases. This new emphasis has stimulated progress in several areas. Recent findings suggest that poor early responses to therapy and detection of minimal residual disease at the postremission induction period by immunologic methods are reliable indicators of an adverse prognosis warranting modification of treatment. In this regard, timely administration of intensified chemotherapy, including a second reinduction/intensification phase, may nullify the adverse prognosis conferred by a delayed response to induction therapy. Comparative analysis of survival outcomes in T-cell patients who received chemotherapy or cranial irradiation (12 Gy) to prevent overt leukemia in the central nervous system suggests that the latter modality should be retained for cases with leukocyte counts > 100 x 10(9)/L. Recent innovations in histocompatibility matching, prevention of graft-versus-host disease, and antiviral prophylaxis have enhanced the applicability of hematopoietic stem cell transplantation, making this procedure available to candidates lacking matched sibling donors. Finally, demonstration that acute lymphoblastic leukemia has an angiogenic phase in bone marrow raises the possibility of effective treatment with antiangiogenic agents, such as endostatin. Remaining challenges in the treatment of childhood leukemia include 1) the development of specific and more effective therapy for high-risk cases and 2) the reduction of long-term complications associated with intensive chemotherapy and cranial irradiation.     

Ongoing trials in patients with head and neck cancer

Treatment of squamous cell carcinoma of the head and neck has recently undergone several important changes. New approaches to treating these tumours are now being evaluated. An overview of the surgical, radiotherapeutic and chemotherapeutic therapies or multimodality approaches currently under study are described. In addition, the design of ongoing chemoprevention trials is reported.     

The role of chemotherapy in head and neck cancer

We studied the effect of cytoreductive chemotherapy in head and neck cancer and analyzed it in terms of efficacy, remission rates, and duration, as well effect on survival. Single-agent chemotherapy, which formerly was used as a palliative therapy in recurrent and metastatic disease, had little affect on survival. More recently, multi-agent chemotherapy trials have shown significantly higher response rates, but this success has not translated into an added survival benefit. These findings led to the introduction of multi-agent chemotherapy into the induction (neoadjuvant) clinical setting. In these clinical circumstances, better objective response rates were found, particularly in the previously untreated patient. Although this therapy has resulted in better control of local disease, the impact on survival is not yet clear. Adjuvant chemotherapy is most useful in patients who have a high risk of relapse. Therapy appears to decrease its incidence, particularly at distant sites. Finally, chemoradiation trials have shown that this treatment provides a survival advantage, but at the cost of a significant increase in toxicity.     

Delayed hypersensitivity skin test in head and neck cancer

A brief introduction is given stressing the importance of host reactions against tumour specific antigens. Two groups of patients are presented. Positive tests are associated with a better prognosis in both groups. Energy is commonly associated with widespread disease, but other factors appear to be concerned as well. Immune competence is impaired soon after surgery, but as time progresses this appears to recover. Tumour bulk appears to be the biggest barrier to the immune mechanism and it would appear that the role of immunotherapy in the future will be to supplement more conventional methods of treatment, especially surgery.     

Comparison between radiation-induced cell cycle delay in lymphocytes and radiotherapy response in head and neck cancer

Two experiments examined the frequency specificity of habituation of the acoustic startle response in the rat. Following the long-term habituation of startle to one of two pure tone stimuli in Experiment 1, animals were presented with the other stimulus. Startle response asymptotes were unaffected by this change in stimulus frequency. Short-term habituation of startle also was insensitive to stimulus frequency. In Experiment 2, pure tone stimuli were used to provoke both a startle response and the interruption of drinking. Long-term habituation of startle to either stimulus was unaffected by a change in frequency. Animals that received the two stimuli on alternating days showed as rapid a habituation as did the groups receiving only one stimulus frequency during acquisition. Conversely, the lick suppression measure was found to be frequency specific. Lick suppression durations rose to pre-habituation levels when the frequency of the stimulus was changed. Animals that received the two stimuli on alternating days showed retarded habituation compared to those groups presented with only one stimulus frequency during acquisition. Although long-term habituation of startle is not stimulus specific, it is mediated by central processes and thus remains a valuable model in the study of neurophysiological mechanisms of behavioral change.