Deficient immunity in head and neck cancer due to excessive monocyte production of prostaglandins

Monocytes from patients with head and neck cancer produce excessive PGE₂ which seems to be associated with decreased lymphoproliferation in vitro. This may be n pathological exaggeration of a normal homeostatic mechanism. It is speculated that a stimulus for excessive PGE₂ production could be immune complexes. Although PGE₂ suppresses many important immune processes relevant for neoplasia, it can also have complex and diverse effects on tumor cells. Caution should be exercised with human trials of prostaglandin synthctase inhibitors such as indomethacin.     

French consensus on management of head and neck cancer surgery during COVID-19 pandemic

In the context of the current pandemic, there is a need for specific advice concerning treatment of patients with Head and Neck cancers. The rule is to limit as much as possible the number of patients in order to reduce the risks of contamination by the SARS-Cov-2 virus for both patients and the caregivers, who are particularly exposed in ENT. The aim is to minimize the risk of loss of opportunity for patients and to anticipate the increased number of cancer patients to be treated at the end of the pandemic, taking into account the degree of urgency, the difficulty of the surgery, the risk of contaminating the caregivers (tracheotomy) and the local situation (whether or not the hospital and intensive care departments are overstretched).     

Evaluation of syncope from head and neck cancer

Five patients suffering from recurrent syncope in association with metastatic squamous cell carcinoma of the head and neck were examined. Two patients had exhaustive diagnostic work-up for syncope, which eventually disclosed previously undiagnosed, recurrent squamous cell carcinoma. Case reports describe glossopharyngeal neuralgia, a well recognized cause of syncope in the head and neck cancer patient, characterized by acute unilateral head or neck pain preceding each syncopal episode. The literature on the diagnosis of syncope is reviewed, and the syncopal mechanisms unique to the head and neck cancer patient are analyzed and discussed. A diagnostic approach to syncope in head and neck cancer is proposed.     

Interleukin-2 release from lymphocytes of patients with head and neck cancer

Interleukin-2 (IL-2) plays a central role in cellular immune regulation. In vitro this cytokine is secreted after mitogenic stimulation with phorbolester (PMA), phytohemagglutinin A (PHA), or the monoclonal T cell antibody OKT3. In our experiments the IL-2 concentration was measured in a biologic system using an IL-2-dependent murine cytotoxic T cell line. Control subjects who were age-matched to patients with head and neck cancers did not show an altered IL-2 production in vitro, irrespective of whether they were accustomed to high alcohol consumption or cigarette smoking. Patients with cancer of the larynx did not differ significantly from control subjects. Most prominent was the significant reduction in IL-2 release of patients with cancer of the oropharynx and in patients with positive lymph nodes in the neck. Impaired IL-2 secretion in head and neck cancer patients may therefore be an additional prognostic indicator worthy of further investigation.     

Altered genotoxicity in mucosal cells of head and neck cancer patients due to environmental pollutants

The complexity of carcinogenesis in squamous cell cancer (SCC) of the upper aerodigestive tract requires examining environmental risk factors, including mutagen sensitivities to xenobiotics. Three environmental, occupational, and habitual pollutants – dibutylphthalate (DBP), diisobutylphthalate (DiBP), and N′nitrosodiethylamine (NDELA) – were submitted to genotoxicity testing on mucosal biopsy specimens of tumor and nontumor patients in vitro. The single-cell microgel electrophoresis (Comet) assay was applied to detect DNA strand breaks in human epithelial cells of the pharynx and larynx from nontumor patients, patients with SCC of the oropharynx and patients with SCC of the larynx. Genotoxicity was found for DBP, DiBP, and NDELA in cells derived from nontumor and tumor patients. With respect to phthalates, Olive tail moment (OTM) levels were higher in patients with SCC of the oropharynx and SCC of the larynx (P < 0.01), the latter showing even more pronounced genotoxicity for DiBP. Testing epithelial cells of the patients with either oropharyngeal or laryngeal SCC for NDELA demonstrated results similar to the nontumor patients. Present findings indicate heterogeneous mutagen sensitivities to some but not all xenobiotics. Received: 25 May 1999 / Accepted: 15 October 1999     

Pediatric head and neck injuries due to golf cart trauma

IntroductionGolf carts are increasingly used off the golf course and are often viewed as innocuous modes of transportation. However, research has shown they can cause significant injuries, particularly to children.ObjectivesAnalyze golf cart related head and neck injuries in children and adults from a national database.MethodsThe National Electronic Injury Surveillance System (NEISS) was queried for golf cart injuries. The NEISS tracks consumer product related injuries from a sampling of approximately 100 emergency departments across the United States. Age, general diagnosis (concussion, fracture, laceration), body-part injured, disposition (hospitalized, discharged), location injury occurred, and mechanism of injury were analyzed.ResultsOver an 11-year period, a total of 3433 total patients were identified. There were 1471 children (16 years old or younger), which compromised 42.9% of the cohort. Children were injured at home or on the road 44.7% of the time compared to only 16.6% of adults (p < 0.003). Children injured their head or neck 42.6% of the time compared to 28.6% of adults (p < 0.0001). Adults who were hit by a car while riding a golf cart or were ejected from the golf cart 44.6% of the time compared to 61.7% of children (p < 0.0001). There were 3.9% of children with a face, head, or neck fracture compared to only 2.4% of adults (p = 0.01).ConclusionChildren are more vulnerable to golf cart related injuries, specifically to the head and neck.     

Adaptation to surgery for head and neck cancer

We examined the postoperative adjustment of 45 patients who underwent surgery for cancers of the head and neck: 23 who had laryngeal cancer, 18 who had oral cavity/oropharyngeal cancers, and 4 who had cancers of other sites. Patients were assessed preoperatively, and at 3 months and 9 to 12 months postsurgery. Interviews and questionnaires were used to assess depression, body image, limitations, pain, financial problems, need for help at home, and social interaction. Results revealed that pain, fatigue, weakness, and loss of speech were major concerns. Pain and financial concerns were worst at 3 months and then improved. Physical limitations increased steadily with time. Depression was a major factor in patients with oral cavity and oropharyngeal cancers. Of note, patients who underwent postoperative radiation therapy had the most difficulty adapting to their illness and treatment, with persistent limitations in function and social isolation. The implications of these findings are discussed.     

Distant lymphatic metastasis from head and neck cancer.

A predictable pattern of metastasis based on tumor histology and site of origin has been well documented for most cancers that arise in the head and neck region. The current study demonstrates that this predictable pattern of metastasis can be significantly impacted by previous therapy, resulting in unusual patterns of metastasis in patients with recurrent tumors. A retrospective case series of 5 patients with head and neck carcinomas who developed metastases to distant lymph nodes is presented. All patients underwent surgery and radiotherapy to the primary tumor and regional lymphatics at the time of their initial treatment. All of the patients developed a local recurrence less than a year before the detection of distant lymphatic metastases. Cytology or excision confirmed metastases to the axillary, inguinal, or anterior intercostal lymph nodes. All of the patients underwent aggressive surgery for attempted cure of the local recurrence shortly before the presence of distant lymphatic metastases was clinically recognized. The metastatic workup of patients with carcinomas of the head and neck frequently includes examination of the regional lymph nodes as well as chest radiography, liver function tests, and serum calcium determination. This evaluation may fail to detect metastases to distant lymph nodes in patients who present with recurrent or second primary cancers. Such patients should undergo careful examination of all major lymph node-bearing regions of the body when being evaluated for the presence of distant metastases.     

Unintended benefits of immunosupression on autoimmune disease due to chemoradiation therapy for head and neck cancer

The immune system is an important factor in the host's defenses against cancer. Immunosupression by radiation and/or chemotherapy is often associated with systemic and hematologic complications, opportunistic infections, and the development of malignancies, but immunosupression can also have beneficial effects, which are sometimes incidental. We report 2 patients with autoimmune diseases where immunosupression had beneficial effects. The first case is about a patient with carcinoma of the tonsil, with severe rheumatoid arthritis, who was treated with chemoradiation, which resulted in remission of his arthritis. The second case is about a patient with severe atopic eczema who was on long-term treatment with psoralen and ultraviolet A radiation and azathioprine; the patient developed metastatic carcinoma of the lip, which was treated with surgery and radiation that resulted in complete remission of his eczema.     

Perioperative mortality in oncologic head and neck surgery

OBJECTIVE: The aim of this study was to establish the causes of perioperative mortality after head and neck oncologic surgery, to improve operative strategies and surgery procedures, and to reduce postoperative complications. SETTING: University Hospitals of Strasbourg, Head and Neck Department. PATIENTS AND METHODS: The medical files of patients who died within 30 days of presentation with epidermoid carcinoma of the head or neck were analyzed; criteria included age, sex, medical history, and the location and stage of development of the tumour. MEASUREMENT METHOD: The causes of death are discussed with reference to the pre- and postmortem observations. RESULTS: In this study, the perioperative mortality rate was 3.07%. It depended more on tumour stage and the medical history of the patient than on tumour location and the age of the patient. The responsibility of the medical team itself was involved in some cases. DISCUSSION AND CONCLUSION: The study shows the difficulty of establishing the cause of death of weakened patients who have undergone a heavy surgical operation. Although the majority of deaths recorded are considered to have been unavoidable, for a small number of them, the absence of vital function monitoring over the first days after the operation was a contributory cause. Perioperative mortality has greatly decreased over the last 30 years and is, at present, almost nonexistent during anesthesia in head and neck surgery.     

Combination nonviral interleukin-2 gene immunotherapy for head and neck cancer: from bench top to bedside

OBJECTIVE/HYPOTHESIS: Intralesional delivery of cytokine genes has emerged as a promising therapeutic strategy for the treatment of cancer. In addition to the therapeutic effect of the delivered cytokine gene, the components of the gene delivery system also have been shown to induce beneficial immune responses. On the basis of these principles, we hypothesized that a molecular therapy could be developed that would provide synergistic antitumor activity by way of intralesional expression of interleukin (IL)-2 from a recombinant plasmid combined with induction of endogenous interferon (IFN)-gamma and IL-12 cytokines by immunostimulatory DNA. Our objective in these studies was to create and optimize a novel formulation of cationic lipid and DNA that generates local production of IL-2 protein within a targeted tumor environment with concomitant induction of the antitumor cytokines IFN-gamma and IL-12. STUDY DESIGN: Prospective laboratory drug development plan that would produce human clinical trials. MATERIALS AND METHODS: Engineered bacterial plasmids containing a cytomegalovirus promoter (CMV)-IL-2 expression cassette were specifically formulated with cationic lipids and optimized for antitumor effect in a floor of mouth murine tumor model. The treated tumors were assayed for local expression of IL-2 and concurrent expression of secondary cytokines IFN-gamma and IL-12. Established tumors in C3H/HeJ mice were treated with various IL-2 gene formulations, and clinical and immunologic responses were evaluated. Immunologic studies were performed and included cytolytic T-cell assays and cytokine expression profiles. For human clinical trials, a phase I 10 patient formulated IL-2 gene therapy study was completed. Subsequently, two large scale, phase II multi-institutional and multi-international studies were initiated comparing non-viral IL-2 gene therapy to palliative methotrexate chemotherapy or in combination with cisplatin. RESULTS: In the preclinical stage, maximum tumor inhibition in animal models was obtained using IL-2 plasmid formulated with 1,2-dioleyloxypropyl-3-trimethyl ammonium chloride (DOTMA):cholesterol (1:1 mol:mol) at a plasmid:lipid charge ratio of 1:0.5 (-/+). Cationic lipid formulated IL-2 plasmid significantly inhibited tumor growth compared with formulated control plasmid (P < .01) or vehicle (lactose; P < .01). Consistent with previously reported studies of the immunostimulatory activity of DNA of bacterial origin, treatment of tumors with control plasmid in cationic lipid formulation induced production of endogenous IFN-gamma and IL-12 but not IL-2. Treatment of tumors with formulated IL-2 plasmid produced IL-2 protein levels that were 5-fold over background and increased IFN-gamma by 32-fold (P < .001) and IL-12 by 5.5-fold (P < .001) compared with control plasmid formulations. The phase I human trial demonstrated dose escalation safety, which was its primary objective, and there was one anecdotal reduction in tumor size. The phase II studies have been initiated and focus on either comparing the novel nonviral IL-2 gene immunotherapy formulation alone to methotrexate or comparing IL-2 gene therapy in combination with cisplatin in recurrent or unresectable patients with head and neck squamous cell carcinoma. CONCLUSIONS: The preclinical data provided proof of principle for matching a delivered IL-2 transgene with an immunostimulatory nonviral formulation to enhance intralesional production of therapeutic cytokines for the maximization of antitumor response. Human clinical trials have demonstrated this novel therapy to be safe in the human clinical setting. Phase II trials have been initiated to assess efficacy and feasibility as a single or combination therapy for head and neck cancer.     

Papillomavirus and head and neck cancer

Tobacco and alcohol consumption are the main risk factors for head and neck cancers. Papillomavirus (HPV) infection was recently associated with the development of malignant tumors of the oropharynx, according to molecular and biological arguments. We describe the oncogenic mechanisms of HPV infections, the epidemiological and clinical aspects of associated head and neck cancers, their prognosis, and issues of specific therapeutic strategies.     

HPV and head and neck cancer

Head and neck cancer is frequent worldwide and oropharyngeal locations are presently sharply on the increase, in relation with an increasing incidence of oropharyngeal infection by oncogenic type-16 human papillomavirus (HPV). The clinical and biologic profile of these patients is distinct from that of other oropharyngeal carcinoma patients, with earlier onset, cystic cervical nodes and basaloid carcinoma histopathology. Detection of intratumoral viral DNA is essential to confirm the role of HPV, and E6/E7 mRNA expression is the most relevant indicator for stratification. Several methods can reveal intratumoral oncogenic HPV DNA, but PCR with hybridization is the most sensitive and most widely used. According to several reports, prognosis in terms of survival and locoregional control is better in HPV-positive oropharyngeal carcinoma than in oropharyngeal carcinoma associated with smoking and alcohol consumption. The future lies in vaccination, but further studies will determine whether the rate of oropharyngeal carcinoma falls in women vaccinated against cervical cancer.