David J. Terris

HYPOXIA IN head and neck tumors limits the efficacy of conventional radiotherapy.1-4 The success of radiotherapy requires sufficient cellular oxygen, because irradiation induces damage and apoptosis by converting oxygen into reactive oxygen species, which in turn breaks DNA strands. Olive5 confirmed that tumor cells from mice breathing air during irradiation suffer more DNA damage than cells from mice asphyxiated before exposure. Since strategies for overcoming tumor hypoxia are becoming available, the assessment of tumor oxygenation is important because it may allow for customization of nonsurgical treatment.

Objective To examine the feasibility of endoscopic resection of the submandibular gland in a porcine model.Study Design Experimental, nonrandomized prospective study.Methods Twelve endoscopic submandibular gland resections were performed on seven Yorkshire adult pigs using a combination of balloon dissection and low‐pressure CO₂ insufflation. The operative time, blood loss, blood pressure, oxygen saturation, temperature, arterial blood gas values, and weight of the glands were measured.Results All 12 submandibular gland resections were successfully performed endoscopically, and no conversions to open resection were necessary. The procedures lasted 42 to 140 minutes (median duration, 59 min). The median estimated blood loss was 15 mL. The submandibular glands weighed 13.3 ± 1.5 g. The arterial blood pH varied from a decrease of 0.08 to an increase of 0.09 units from the beginning to the end of the operation. Similarly, the arterial CO₂ pressure at the end of the case varied from a decrease of 15.8 to an increase of 16.2 mm Hg from the starting value. The presence of normal glandular architecture and lack of trauma or thermal injury were confirmed histologically. There were no cases of pneumothorax or air embolism, and no animals had to be killed. In one animal, a modest amount of subcutaneous emphysema could be appreciated, which was confined to the area over the operative pocket.Conclusion Endoscopic resection of the submandibular gland is possible by combining balloon dissection with low‐pressure CO₂ insufflation, thereby avoiding complications of high‐pressure insufflation such as pneumothorax and air embolism.

TRANSFUSION OF BLOOD from allogeneic (heterologous) donors has a long and interesting history in the practice of medicine. Before the ABO blood group system was discovered by Landsteiner a century ago,¹ transfusions were considered ineffective and dangerous. The recognition of the ABO and Rh blood groups and development of preservation techniques for storing allogeneic blood led to the increased application of transfusion therapy with dramatic reductions in morbidity and mortality from hemorrhage during surgery. The impact of blood transfusions on the recipient's cellular immune system was appreciated in the 1970s, when the beneficial effect of pretransplant allogeneic transfusion on renal transplant survival was described.² Since the 1980s, the association between transfusion and increased cancer recurrence and decreased survival has been reported in a number of epidemiologic and experimental studies.^3-8 Although the preponderance of data suggests an adverse association between allogeneic blood transfusion and cancer outcome, this association remains inconclusive. Nevertheless, this potential adverse effect combined with the small risk of infectious transmission has heightened interest in the use of autologous blood transfusion. The advantages of autologous blood transfusion with respect to cancer outcomes have been suggested in clinical reports.^3,8

OBJECTIVE: To determine the true incidence of mucosal injury after radiofrequency ablation of the palate (RFAP) for snoring and mild obstructive sleep apnea, and to evaluate the consequences of this injury.STUDY DESIGN AND SETTING: A prospective, nonrandomized analysis of RFAP was undertaken at Stanford University Hospital. Endoscopic examinations of the nasal surface of the palate and of the posterior pharyngeal wall were performed to supplement the routine oral cavity examinations in the postoperative period. Visual analog scales of pain were completed by the patients. Twenty‐three patients underwent a total of 54 RFAP procedures using the Somnus system at the recommended level of energy (600 J in the midline palate, and 300 J to each lateral palate).RESULTS: Fourteen of the 23 first stage procedures were associated with a total of 16 mucosal injuries representing an incidence of 60.9%. Mucosal injury at the 1st stage prompted a reduction in energy at the 2nd stage to 500 J in the midline and 250 J laterally; there were 4 injuries among 19 2nd stage procedures (21.1%). The overall incidence of mucosal injury, including stage 3 and 4 procedures, was therefore 42.6%; 37% of these were “occult” (only visualized endoscopically).CONCLUSIONS AND SIGNIFICANCE: RFAP, although intended to be mucosa‐sparing, is nevertheless associated with a high incidence of mucosal injuries, many of which are occult. The occurrence of these mucosal ulcers is usually associated with only a trivial degree of increased pain postoperatively.

Objective The placement of percutaneous endoscopic gastrostomy (PEG) tubes is within the realm of the head and neck surgeon because most are proficient in the use of rigid and flexible esophagoscopes. The ability to provide comprehensive care for the patient with head and neck cancer provides further incentive for the head and neck surgeon to adopt this technique. Although it is a technically simple procedure, the surgeon must be aware of the range of complications that can occur with PEG. We review our experience with PEG focusing on the complications as well as strategies for the prevention and management of these complications.Methods A retrospective review of the records of patients who underwent PEG at Stanford University by the Head and Neck Surgery Service between July 1992 and December 1998 was conducted. A total of 103 patients were identified, of which 84 (82%) were patients with head and neck cancers. Complications associated with PEG were identified. All PEGs were performed using the pull technique.Results There was no mortality associated with the procedure. Minor complications occurred in 11 cases (10.7%). These included cellulitis (4), ileus (3), tube extrusion (1), clogged lumen (1), and peristomal leakage (2). The only major complication was a single case of PEG site metastasis.Conclusion The review of our experience with PEG tube placement revealed a low complication rate. Safe PEG placement was achieved by transillumination of the abdominal wall and confirmation by ballottement. In addition, appropriate patient selection, use of perioperative antibiotics, as well as meticulous post‐procedure care contributed to the low rate of complications. For the patients with head and neck cancer, a barrier should be placed between the tumor and the instrumentation at the time of tube placement.

AUTOLOGOUS NERVE interposition grafts are frequently harvested by head and neck surgeons. The choices for donor nerve include the sural nerve, the greater auricular nerve, and the medial antebrachial cutaneous nerve, among others. The sacrifice of these nerves guarantees some degree of morbidity, including sensory loss, additional incision sites with associated potential complications, and prolonged operative time. Furthermore, autologous nerves may have significant limitations, including caliber mismatch, inadequate length, and susceptibility to crush injury during harvest. An alternative to autologous nerve grafting is, therefore, desirable.

INTERLEUKIN 6 (IL-6) is a cytokine and therefore shares features common to the cytokine family, including a diversity of functions and a variety of sources. Interleukin 6 is synthesized by monocytes and macrophages,¹ T cells,² fibroblasts,³ endothelial cells,^4,5 and astrocytes.⁶ Of interest, IL-6 is structurally homologous to the neurocytokines ciliary neurotrophic factor and leukemia inhibitory factor and also shares a common signal transducer molecule, gp130.^7,8

Introduction There is an increased incidence of cancer in patients after organ transplantation. We reviewed a large series of cardiothoracic transplant recipients to determine the incidence and natural history of head and neck malignancy.Methods A total of 1069 heart (n = 855), heart/lung (n = 111), and lung (n = 103) transplants were performed at Stanford University from January 1968 to February 1998. Demographic data, risk factors, and disease course were evaluated in patients who developed cancer. The mean length of follow‐up was 8.9 ± 5.2 years.Results One hundred twenty patients (11.2%) developed 547 non‐lymphomatous malignancies. The mean number of malignancies per cancer patient was 4.6. The average time from transplantation to development of cancer was 63.1 months. A total of 50.5% of malignancies presented in the head and neck; 96.4% of these were cutaneous in origin and 3.6% were noncutaneous. Of cutaneous malignancies, 79.3% were squamous cell carcinoma and 15.9% were basal cell carcinoma. Cutaneous malignancies most commonly presented on the scalp, cheek, lip, and neck. Noncutaneous malignancies involved the oral cavity (5), thyroid (4), and parotid (1). Thirteen percent of cutaneous head and neck cancers behaved aggressively, requiring e‐tensive management including radical surgery, radiation, and/or chemotherapy. A total of 34.2% of cancer patients developed metastases and 54.9% of cancer patients died as a direct result of cancer. A total of 68% of cancer patients were smokers and 23.8% had significant alcohol use.Conclusion Transplant recipients have an increased incidence of cancer presenting in the head and neck. Malignancies in transplant patients behave more aggressively than in the general population. Recognition of this aggressive biological behavior and heightened cancer surveillance should result in improved outcomes.

Research from JAMA Otolaryngology–Head & Neck Surgery — Delayed Repair of Transected Nerves — Effect of Brain-Derived Neurotrophic Factor

In this study, we have analyzed changes induced by hypoxia at the transcriptional level of genes that could be responsible for a more aggressive phenotype. Using a series of DNA array membranes, we identified a group of hypoxia-induced genes that included plasminogen activator inhibitor-1 (PAI-1), insulin-like growth factor-binding protein 3 (IGFBP-3), endothelin-2, low-density lipoprotein receptor-related protein (LRP), BCL2-interacting killer (BIK), migration-inhibitory factor (MIF), matrix metalloproteinase-13 (MMP-13), fibroblast growth factor-3 (FGF-3), GADD45, and vascular endothelial growth factor (VEGF). The induction of each gene was confirmed by Northern blot analysis in two different squamous cell carcinoma-derived cell lines. We also analyzed the kinetics of PAI-1 induction by hypoxia in more detail because it is a secreted protein that may serve as a useful molecular marker of hypoxia. On exposure to hypoxia, there was a gradual increase in PAI-1 mRNA between 2 and 24 h of hypoxia followed by a rapid decay after 2 h of reoxygenation. PAI-1 levels were also measured in the serum of a small group of head and neck cancer patients and were found to correlate with the degree of tumor hypoxia found in these patients.