Recurrent laryngeal nerve injury in video-assisted thyroidectomy: lessons learned from neuromonitoring.

INTRODUCTION: The objective of the study was to assess the mechanism of recurrent laryngeal nerve (RLN) injury during video-assisted thyroidectomy (VAT). METHODS: The study examined 201 nerves at risk (NAR). VAT with laryngeal neuromonitoring (LNM) was outlined according to this scheme: (a) preparation of the operative space; (b) vagal nerve stimulation (V1); (c) ligature of the superior thyroid vessels; (d) visualization, stimulation (R1), and dissection of the RLN; (e) extraction of the lobe; (f) resection of the thyroid lobe; (g) final hemostasis; (h) verification of the electrical integrity of the RLN (V2, R2). The site, cause, and circumstance of nerve injury were elucidated with the application of LNM. Laryngeal nerve injuries were classified into type 1 injury (segmental) and 2 (diffuse). RESULTS: Fourteen nerves (6.9 %) experienced loss of R2 and V2 signals. 80 percent of lesions occurred in the distal 1 cm of the course of the RLN. The incidence of type 1 and 2 injuries was 71 and 29 % respectively. The mechanisms of injury were traction (70 %) and thermal (30 %). Traction lesions were created during the extraction of the lobe from the mini-incision [point (e)]. Thermal injury occurred during energy-based device use in (f) and (g) circumstances. CONCLUSIONS: RLN palsy still occurs with routine endoscopic identification of the nerve, even combined with LNM. LNM has the advantage of elucidating the mechanism of RLN injury. Traction and thermal RLN injuries are the most frequent lesions in VAT.

Minimally invasive thyroid cancer surgery.

The aim of this paper was to explore the appropriateness and outcomes of minimally invasive thyroid surgery for the management of well-differentiated thyroid cancer. The study is a planned analysis of a prospectively maintained patient database representing a consecutive, single-surgeon experience. A systematic review was undertaken of a series of patients undergoing minimally access surgery for well-differentiated thyroid cancer. Comprehensive demographic data were considered, including age, gender, pathologic findings, complications, and oncologic outcomes. Ninety-two patients with thyroid cancer (mean age =45.6 years) underwent minimally invasive or endoscopic thyroidectomy over a five-year period. Surgical pathology revealed papillary cancer in 76 patients, follicular cancer in 10 patients, Hurthle cell cancer in 3 patients and medullary cancer in 3 patients. There have been no recurrences in any of these patients thus far (with a short median follow-up of 31 months). Excellent cosmetic results have been observed with this minimal access approach. Minimally invasive and endoscopic thyroidectomy can be safely and effectively performed in many patients with low- or intermediate-risk thyroid cancer. In addition to improved cosmesis, many patients experience decreased pain and faster recovery, and are at no increased risk for complications in the hands of high-volume thyroid surgeons.

Endoscopic and robotic thyroidectomy: past and future.

After nearly a century of performing a thyroid-ectomy essentially the way it was described by Theodore Kocher in the nineteenth century, the technique has suddenly and rapidly evolved. It can now be accomplished endoscopically in many patients who therefore benefit from the reduced dissection and smaller incisions associated with the approach. While many of the cosmetic, quality of life, and functional improvements have now been documented, an improved understanding of the procedure and the appropriate indications for its application will continue to develop even as the technique itself evolves, and as new approaches emerge.

Minimally invasive thyroidectomy: an emerging standard of care.

Virtually all disciplines of surgery now offer some version of minimal access surgical techniques. Because of the challenges related to gas insufflation in the head and neck, endoscopic surgery in this region remains in its infancy. Miccoli and his group at the University of Pisa are responsible for developing a surgical approach that relies on endoscopic and ultrasonic technology, which is easily the most widely practiced technique by minimal access surgeons around the globe. Video-assisted thyroid surgical techniques have emerged as the most feasible compromise between ample exposure and minimal access surgery. In addition to the application of technology, modern thyroid surgery incorporates a number of departures from classical training, including marking of the patient upright in the holding area, no or minimal neck extension, infrequent use of a drain, and outpatient surgery. We have emphasized the concept of customizing the procedure to the patient and disease characteristics, rather than the reverse. Therefore, a spectrum of surgical techniques can be helpful, particularly for the inexperienced minimal access thyroid surgeon. Correspondingly, staging of minimally invasive thyroidectomy has been recommended in order to allow for both uniform reporting of outcome measures across patient populations and a logical basis for determining patient eligibility. With an increasingly sophisticated public, which has virtually unlimited access to medical information, the burden will be on the modern thyroid surgeon to stay abreast of surgical or technical improvements that will yield superior outcomes. Looking forward, it would seem inevitable that continued technologic advances will help surgeons achieve less invasive, safer, and more easily performed procedures.

A history of robots: from science fiction to surgical robotics.

Surgical robotics is an evolving field with great advances having been made over the last decade. The origin of robotics was in the science-fiction literature and from there industrial applications, and more recently commercially available, surgical robotic devices have been realized. In this review, we examine the field of robotics from its roots in literature to its development for clinical surgical use. Surgical mills and telerobotic devices are discussed, as are potential future developments.

Occult mucosal injuries with radiofrequency ablation of the palate.

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.

Quantification of nerve tension after nerve repair: correlations with nerve defects and nerve regeneration.

This study tested the validity of a quantitative in vitro nerve-tension-measuring technique, by correlating the tension measurements with functional and morphologic assessments of nerve regeneration. Initially, harvested nerves were used in vitro to determine a K value for lateral displacement in this tissue. Next, this value was used to calculate the tension of nerve repair, following 0-, 3-, 6-, and 9-mm resections of nerves in groups of rats. After quantifying the nerve tensions following excision and repair, the authors determined a sciatic function index to evaluate functional recovery and axon diameter in the animals. Functional recovery was significantly impaired in animals with elevated measurable tension (9.04 +/- 0.74 g in a 6-mm defect, 27.76 +/- 8.86 g in a 9-mm defect), compared to animals with no or 3-mm excision and measured tension of 3.3 +/- 1.09 g or less. Increased tension was also associated with a significant decrease in axon diameter. This study succeeded, therefore, in quantitatively relating the elements of measured nerve tension, nerve gaps, functional nerve recovery, and morphologic regeneration. Quantification of nerve tension by lateral displacement in vivo offers a possible solution to clinical management of nerve gaps, when the choice between primary repair and nerve grafting is not a clear one.

Treatment results and prognostic factors of advanced T3--4 laryngeal carcinoma: the University of California, San Francisco (UCSF) and Stanford University Hospital (SUH) experience.

PURPOSE: To review the UCSF-SUH experience in the treatment of advanced T3--4 laryngeal carcinoma and to evaluate the different factors affecting locoregional control and survival. METHODS AND MATERIALS: We reviewed the records of 223 patients treated for T3--4 squamous cell carcinoma of the larynx between October 1, 1957, and December 1, 1999. There were 187 men and 36 women, with a median age of 60 years (range, 28--85 years). The primary site was glottic in 122 and supraglottic in 101 patients. We retrospectively staged the patients according to the 1997 AJCC staging system. One hundred and twenty-seven patients had T3 lesions, and 96 had T4 lesions; 132 had N0, 29 had N1, 45 had N2, and 17 had N3 disease. The overall stage was III in 93 and IV in 130 patients. Seventy-nine patients had cartilage involvement, and 144 did not. Surgery was the primary treatment modality in 161 patients, of which 134 had postoperative radiotherapy (RT), 11 had preoperative RT, 7 had surgery followed by RT and chemotherapy (CT), and 9 had surgery alone. Forty-one patients had RT alone, and 21 had CT with RT. Locoregional control (LRC) and overall survival (OS) were estimated using the Kaplan--Meier method. Log-rank statistics were employed to identify significant prognostic factors for OS and LRC. RESULTS: The median follow-up was 41 months (range, 2--367 months) for all patients and 78 months (range, 6--332 months) for alive patients. The LRC rate was 69% at 5 years and 68% at 10 years. Eighty-four patients relapsed, of which 53 were locoregional failures. Significant prognostic factors for LRC on univariate analysis were primary site, N stage, overall stage, the lowest hemoglobin (Hgb) level during RT, and treatment modality. Favorable prognostic factors for LRC on multivariate analysis were lower N stage and primary surgery. The overall survival rate was 48% at 5 years and 34% at 10 years. Significant prognostic factors for OS on univariate analysis were: primary site, age, overall stage, T stage, N stage, lowest Hgb level during RT, and treatment modality. Favorable prognostic factors for OS on multivariate analysis were lower N stage and higher Hgb level during RT. CONCLUSION: Lower N-stage was a favorable prognostic factor for LRC and OS. Hgb levels > or = 12.5 g/dL during RT was a favorable prognostic factor for OS. Surgery was a favorable prognostic factor for LRC but did not impact on OS. Correcting the Hbg level before and during treatment should be investigated in future clinical trials as a way of improving therapeutic outcome in patients with advanced laryngeal carcinomas.

Brain-derived neurotrophic factor-enriched collagen tubule as a substitute for autologous nerve grafts.

BACKGROUND: Autologous nerve interposition grafts are frequently harvested by head and neck surgeons. The sacrifice of these donor nerves guarantees some degree of morbidity, including sensory loss, additional incision sites with associated potential complications, and prolonged operative time. An alternative to autologous nerve grafting is, therefore, desirable. OBJECTIVE: To determine if a collagen tubule (CT) filled with either a plain collagen gel or a brain-derived neurotrophic factor (BDNF)-enriched collagen gel could be used to achieve functional and histologic outcomes equivalent to an autologous nerve graft in bridging a 15-mm nerve gap in the rabbit facial nerve. DESIGN: A prospective, randomized, blinded animal study with a control group. METHODS: Thirty rabbit facial nerves were resected (15-mm segments) to create nerve gaps. The gaps were bridged using 1 of 3 methods, assigned randomly: a reversed facial nerve (control), a collagen gel-filled CT, or a BDNF-enriched collagen gel-filled CT. The animals were evaluated after 6 weeks in a blinded fashion for functional nerve recovery, axon count, and axonal diameter. RESULTS: There were no significant differences between the autologous nerve graft group, the collagen gel-filled CT group, or the BDNF-enriched collagen gel-filled CT group (n = 10 for each group) for functional nerve recovery (P =.94). The mean axon count and the mean axonal diameter were highest in the BDNF-enriched collagen gel-filled CT group, but these differences failed to reach statistical significance (P =.18 and.96, respectively). CONCLUSIONS: Collagen tubules filled with BDNF-enriched collagen gel appear to be at least as good as autologous nerve grafts for bridging short facial nerve gaps. Larger experimental studies are warranted to determine if clinical trials are justified.

Percutaneous endoscopic gastrostomy: strategies for prevention and management of complications.

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.

Composite dendritic cell neoplasm (NOS) and small lymphocytic lymphoma.

This report describes a composite (or "collision") of a dendritic cell neoplasm and small lymphocytic lymphoma. It represents the seventh example of dendritic cell neoplasia occurring in the setting of low-grade B-cell malignancy and the third example of a composite tumor, in which both neoplasms were present within the same lymph node. The small lymphocytic lymphoma component exhibited a typical CD20+, CD5+, and CD23+ immunophenotype. The dendritic cell neoplasm exhibited reactivity with CNA-42, but nonreactivity for CD21, CD35, smooth muscle actin, desmin, and epithelial membrane antigen (EMA). Equivocal cytoplasmic staining was seen for S100p, CD68, and Factor XIIIa. Ultrastructurally, the dendritic cell neoplasm exhibited desmosomes, rough endoplasmic reticulum, cytoplasmic intermediate filaments, and intercellular collagen. Because the immunophenotype and ultrastructure did not correspond to one of the five recognizable dendritic cell subtypes, the neoplasm was designated dendritic cell neoplasm, not otherwise specified (NOS). Polymerase chain reaction (PCR) analysis for immunoglobulin heavy chain gene rearrangements performed on individual components of the composite tumor demonstrated rearrangement within the small lymphocytic lymphoma component, but none in the dendritic cell component. The lack of an immunoglobulin heavy chain gene rearrangement within the dendritic cell component argues against a transformational event and supports the concept that these separate neoplasms represent a true "collision" or composite lesion.

Treatment results of carcinoma in situ of the glottis: an analysis of 82 cases.

OBJECTIVES: To evaluate the results of different treatment modalities for carcinoma in situ of the glottis, and to identify important prognostic factors for outcome. DESIGN: Review of 82 cases treated definitively for glottic carcinoma in situ between 1958 and 1998. The median follow-up for all patients was 112 months, and 90% had more than 2 years of follow-up. SETTING: Academic tertiary care referral centers. INTERVENTION: Fifteen patients were treated with vocal cord stripping (group 1), 13 with more extensive surgery (group 2) including endoscopic laser resection (11 patients) and hemilaryngectomy (2 patients), and 54 with radiotherapy (group 3). Thirty patients had anterior commissure involvement and 9 had bilateral vocal cord involvement. Radiotherapy was delivered via opposed lateral fields at 1.5 to 2.4 Gy per fraction per day (median fraction size, 2 Gy), 5 days per week. The median total dose was 64 Gy, and the median overall time was 47 days. MAIN OUTCOME MEASURES: Initial locoregional control (LRC), ultimate LRC, and larynx preservation. RESULTS: The 10-year initial LRC rates were 56% for group 1, 71% for group 2, and 79% for group 3. Of those who failed, the median time to relapse was 11 months for group 1, 17 months for group 2, and 41 months for group 3. Univariate analysis showed that the difference in initial LRC rates between groups 1 and 3 was statistically significant (P =.02), although it was not statistically significant on multivariate analysis (P =.07). Anterior commissure involvement was an important prognostic factor for LRC on both univariate (P =.03) and multivariate (P =.04; hazard ratio, 1.6) analysis, and its influence appeared to be mainly confined to the surgically treated patients (groups 1 and 2). The 10-year larynx preservation rates were 92% for group 1, 70% for group 2, and 85% for group 3. Anterior commissure involvement was the only important prognostic factor for larynx preservation (P =. 01) on univariate analysis. All but 2 patients in whom treatment failed underwent successful salvage surgery. Voice quality was deemed good to excellent in 73% of the patients in group 1, 40% in group 2, and 68% in group 3. CONCLUSIONS: Treatment of carcinoma in situ of the glottis with vocal cord stripping or more extensive surgery or radiotherapy provided excellent ultimate LRC and comparable larynx preservation rates. Anterior commissure involvement was associated with poorer initial LRC and larynx preservation, particularly in the surgically treated patients. The choice of initial treatment should be individualized, depending on patient age, reliability, and tumor extent. Pretreatment and posttreatment objective evaluation of voice quality should be helpful in determining the best therapy for these patients.

Pancreatic tumors show high levels of hypoxia.

PURPOSE: Because of the dismal outcomes of conventional therapies for pancreatic carcinomas, we postulated that hypoxia may exist within these tumors. METHODS AND MATERIALS: Seven sequential patients with adenocarcinomas of the pancreas consented to intraoperative measurements of tumor oxygenation using the Eppendorf (Hamburg, Germany) polargraphic electrode. RESULTS: All 7 tumors demonstrated significant tumor hypoxia. In contrast, adjacent normal pancreas showed normal oxygenation. CONCLUSION: Tumor hypoxia exists within pancreatic cancers.

Reliability of the Muller maneuver and its association with sleep-disordered breathing.

OBJECTIVES/HYPOTHESIS: Use of the Muller maneuver (MM) in the evaluation of patients with obstructive sleep apnea is controversial. One criticism of this test is that it is somewhat subjective. Our objective is to explore the reliability of this technique and its association with sleep-disordered breathing. STUDY DESIGN: Prospective study performed in an academic tertiary care center. METHODS: An analysis of MM scores from 180 consecutive patients obtained independently by two examiners was completed. These scores were compared with each other and with the apnea-hypopnea index (AHI) obtained from polysomnographic studies. RESULTS: Collapse of the soft palate (PAL), lateral pharyngeal wall (LPW), and base of the tongue (BOT) was rated on a five-point scale (0-4). The mean scores determined by the faculty examiner were 2.47, 2.06, and 1.58, respectively; the mean scores determined by the resident examiner were 2.34, 2.25, and 1.48, respectively. The scores of the two examiners correlated to within +/- 1 unit 83.9% of the time at the PAL, 91.1% at the LPW, and 85.0% at the BOT. The degree of correlation was not influenced by year of training of the resident. When the AHI was converted to a four-point scale based on severity, the score correlated within +/- 1 of the average MM score 72.1% of the time. CONCLUSIONS: Despite the subjective nature of the MM, the five-point scale can be used by independent examiners to achieve an evaluation of the upper airway that is reproducible. The preoperative severity of sleep-disordered breathing based on the AHI is moderately correlated with the MM score.

Factors related to outcome of salvage therapy for isolated cervical recurrence of squamous cell carcinoma in the previously treated neck: a multi-institutional study.

OBJECTIVE: The goal was to identify factors associated with the outcome of salvage therapy for patients with isolated cervical recurrences of squamous cell carcinoma in the previously treated neck (ICR-PTN). STUDY DESIGN AND SETTINGS: A tumor registry search for ICR-PTN patients was performed at 7 participating institutions, and the charts were reviewed. Kaplan-Meier plots for survival and time until re-recurrence were used to evaluate the significance of associated variables. RESULTS: Median survival and time until re-recurrence were both 11 months. Survival was better in patients with the following characteristics: nonsurgical initial neck treatment, negative initial disease resection margins, no history of prior recurrence, ipsilateral location of the ICR-PTN relative to the primary, and use of surgical salvage. CONCLUSIONS: By pooling the experience of 7 US tertiary care medical centers, we have identified 5 factors that are associated with outcome of salvage therapy for ICR-PTN. SIGNIFICANCE: Consideration of these factors, as well as the reviewed literature, should facilitate patient selection for salvage protocols.

Peripheral nerve regeneration in interleukin 6-deficient mice.

BACKGROUND: Interleukin 6 (IL-6) is a multifunctional cytokine with effects on central and peripheral neurons. OBJECTIVE: To investigate the role of IL-6 in peripheral nerve regeneration by comparing IL-6 knockout and wild-type mice in a sciatic nerve model of injury and repair. DESIGN/SUBJECTS: Forty C57/BL6 (wild-type) and 40 IL-6 knockout mice were randomly assigned to 1 of 4 groups: sham surgery, sciatic nerve crush injury, sciatic nerve transection without repair, and sciatic nerve transection with epineurial suture repair. Walking tracks were assessed preoperatively and postoperatively at 10-day intervals for 50 days by means of a previously described mouse sciatic functional index. Distal segments of the sciatic nerves were harvested at the completion of the study for histomorphometric evaluation. RESULTS: The wild-type and knockout mice that underwent sham surgery showed similarly unimpaired function (P =.64 on day 50). The IL-6 knockout mice with the crush injury demonstrated decreased function on day 10 compared with the wild-type mice (P<.01) but completely recovered by day 40 (P =.55). Both IL-6 knockout and wild-type mice that underwent nerve transection without repair failed to recover function (P =.06 on day 50). There was no statistical difference in recovery between wild-type and IL-6 knockout mice that underwent nerve transection with epineurial suture repair (P =.30 on day 50). The morphometric data showed no significant differences in distal axon count between the wild-type and knockout mice after suture repair or crush injury (P>.32). CONCLUSIONS: The absence of IL-6 does not appear to impair peripheral nerve recovery after sciatic nerve injury. Although in vitro and in vivo studies suggest a role for IL-6 in peripheral nerve physiology, this cytokine does not appear to have a substantial effect on functional recovery in a mouse sciatic nerve injury and repair model.

Head and neck cancer in cardiothoracic transplant recipients.

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 extensive 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.

Head and neck cancer: the importance of oxygen.

OBJECTIVES: To use recently introduced polarographic technology to characterize the distribution of oxygenation in solid tumors, explore the differences between severe hypoxia and true necrosis, and evaluate the ability to predict treatment outcomes based on tumor oxygenation. STUDY DESIGN: Prospective, nonrandomized trial of patients with advanced head and neck cancer, conducted at an academic institution. METHODS: A total of 63 patients underwent polarographic oxygen measurements of their tumors. Experiment 1 was designed to determine whether a gradient of oxygenation exists within tumors by examining several series of measurements in each tumor. Experiment 2 was an analysis of the difference in data variance incurred when comparing oxygen measurements using oxygen electrodes of two different sizes. Experiment 3 compared the proportion of tumor necrosis to the proportion of very low (< or =2.5 mm Hg) polarographic oxygen measurements. Experiment 4 was designed to explore the correlation between oxygenation and treatment outcomes after nonsurgical management. RESULTS: No gradient of oxygenation was found within cervical lymph node metastases from head and neck squamous cell carcinomas (P > .9). Tumor measurements achieved with larger (17 microm) electrodes displayed smaller variances than those obtained with smaller (12 microm) electrodes, although this difference failed to reach statistical significance (P = .60). There was no correlation between tumor necrosis and the proportion of very low (< or =2.5 mm Hg) oxygen measurements. There was a nonsignificant trend toward poorer locoregional control and overall survival in hypoxic tumors. CONCLUSIONS: Hypoxia exists within cervical lymph node metastases from head and neck squamous carcinomas, but the hypoxic regions are distributed essentially randomly. As expected, measurements of oxygen achieved with larger electrodes results in lowered variance, but with no change in overall tumor mean oxygen levels. Polarographic oxygen measurements are independent of tumor necrosis. Finally, oxygenation as an independent variable is incapable of predicting prognosis, probably reflecting the multifactorial nature of the biological behavior of head and neck cancers.

Delayed repair of transected nerves: effect of brain-derived neurotrophic factor.

OBJECTIVE: To determine if administration of brain-derived neurotrophic factor (BDNF) after peripheral nerve transection can improve the functional outcome in situations where epineurial repair must be delayed. DESIGN: Randomized, blinded, controlled trial. SUBJECTS: Thirty-four Sprague-Dawley rats. INTERVENTION: Sciatic nerves were transected and, after a 2-week delay, repaired with epineurial sutures. Animals were assigned to receive daily administration of lactated Ringer solution (LR [control] group); BDNF delivered at the time of nerve transection through 2 weeks after nerve repair, for a total of 4 weeks (BDNF-early group); or BDNF delivered at the time of nerve repair through 2 weeks after repair (BDNF-late group). Outcome was assessed using sciatic functional indices (SFIs) and histomorphometric analysis. RESULTS: The SFI maximal recovery was superior in the BDNF groups, but this difference did not reach statistical significance (SFI, -90.1+/-9.6 [LR group], -85.7+/-7.6 [BDNF-early group], and -84.6+/-4.8 [BDNF-late group], where normal function is 0 and complete loss of function is -100; P = .27). The mean axon diameter tended to be greater in the BDNF groups compared with the LR group, i.e., 2.43+/-0.23 microm (LR group), 2.80+/-0.44 microm (BDNF-early group), and 2.83+/-0.38 microm (BDNF-late group) (P = .05). CONCLUSIONS: The local administration of BDNF to nerves that underwent transection and then repair after a delay resulted in an increase in axonal diameters and maximal SFIs, a difference that did not reach statistical significance. The timing of BDNF administration after nerve transection did not affect neuronal regeneration.

Candidate genes for the hypoxic tumor phenotype.

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.