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.

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.

DNA damage measured by the comet assay in head and neck cancer patients treated with tirapazamine.

Tirapazamine (TPZ) [3-amino-1,2,4-benzotriazine 1,4-dioxide, SR4233, WIN 59075, and Tirazone] is a novel anticancer drug that is selectively activated by the low oxygen environment in solid tumors. By killing the radioresistant hypoxic cells, TPZ potentiates the antitumor efficacy of fractionated irradiation of transplanted tumors in mice. As this cell kill is closely correlated with TPZ-induced DNA damage, we investigated whether human head and neck cancers would show DNA damage similar to that seen in mouse tumors following TPZ administration. TPZ-induced DNA damage in both transplanted tumors in mice and in neck nodes of 13 patients with head and neck cancer was assessed using the alkaline comet assay on cells obtained from fine-needle aspirates. The oxygen levels of the patients' tumors were also measured using a polarographic oxygen electrode. Cells from the patients' tumors showed DNA damage immediately following TPZ administration that was comparable to, or greater than, that seen with transplanted mouse tumors. The heterogeneity of DNA damage in the patients' tumors was greater than that of individual mouse tumors and correlated with tumor hypoxia. The similarity of TPZ-induced DNA damage in human and rodent tumors suggests that tirapazamine should be effective when added to radiotherapy or to cisplatin-based chemotherapy in head and neck cancers.

Activation of the heat shock transcription factor by hypoxia in normal and tumor cell lines in vivo and in vitro.

Cells exposed to hypoxia increase their synthesis of a specific set of proteins called oxygen regulated proteins. Recently, three of these proteins have been identified as hemoxygenase, Glucose Regulated Protein 78 kilodaltons and Glucose Regulated Protein 94 kilodaltons. In contrast, reoxygenation from hypoxic conditions increases the synthesis of the heat shock proteins. Although the molecular signals required for regulation of both sets of proteins by hypoxia and reoxygenation are still under investigation, it is known that their expression is regulated at the transcriptional level. This finding suggests that these stresses work either singularly or together to control the activation of nuclear transcription factors which bind distinct regulatory sequences in the promoter region of these genes. One possible nuclear transcription factor which could act as a transcriptional regulator for both hypoxia and reoxygenation gene transcription is the heat shock transcription factor. In this report, we focused on the kinetics of HSF activation by hypoxia in normal and tumor cell lines of murine and human origins. In cell culture, both the normal diploid cell line AG1522 and the tumor cell line JSQ-3 possess the same kinetics of HSF activation (binding to the heat shock element) by hypoxia, with maximal induction at or after 3 hr. We have also shown that the activation of HSF occurs in the SCCVII tumor in vivo without clamping, but not in SCCVII cells grown in monolayers. When SCCVII tumors are dissociated and allowed to reoxygenate in cell culture, HSF binding decreased in 5 hr, and was undetectable after 18 hr. Furthermore, one human tumor biopsy tested for the presence of hypoxia by both the pO2 histograph (Eppendorf, Germany) and HSF binding showed good agreement for both techniques. These results suggest that HSF binding may be a useful marker for monitoring the tumor hypoxia.

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.

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.

Lymph node metastasis in maxillary sinus carcinoma.

PURPOSE: To evaluate the incidence and prognostic significance of lymph node metastasis in maxillary sinus carcinoma. METHODS AND MATERIALS: We reviewed the records of 97 patients treated for maxillary sinus carcinoma with radiotherapy at Stanford University and at the University of California, San Francisco between 1959 and 1996. Fifty-eight patients had squamous cell carcinoma (SCC), 4 had adenocarcinoma (ADE), 16 had undifferentiated carcinoma (UC), and 19 had adenoid cystic carcinoma (AC). Eight patients had T2, 36 had T3, and 53 had T4 tumors according to the 1997 AJCC staging system. Eleven patients had nodal involvement at diagnosis: 9 with SCC, 1 with UC, and 1 with AC. The most common sites of nodal involvement were ipsilateral level 1 and 2 lymph nodes. Thirty-six patients were treated with definitive radiotherapy alone, and 61 received a combination of surgical and radiation treatment. Thirty-six patients had neck irradiation, 25 of whom received elective neck irradiation (ENI) for N0 necks. The median follow-up for alive patients was 78 months. RESULTS: The median survival for all patients was 22 months (range: 2.4-356 months). The 5- and 10-year actuarial survivals were 34% and 31%, respectively. Ten patients relapsed in the neck, with a 5-year actuarial risk of nodal relapse of 12%. The 5-year risk of neck relapse was 14% for SCC, 25% for ADE, and 7% for both UC and ACC. The overall risk of nodal involvement at either diagnosis or on follow-up was 28% for SCC, 25% for ADE, 12% for UC, and 10% for AC. All patients with nodal involvement had T3-4, and none had T2 tumors. ENI effectively prevented nodal relapse in patients with SCC and N0 neck; the 5-year actuarial risk of nodal relapse was 20% for patients without ENI and 0% for those with elective neck therapy. There was no correlation between neck relapse and primary tumor control or tumor extension into areas containing a rich lymphatic network. The most common sites of nodal relapse were in the ipsilateral level 1-2 nodal regions (11/13). Patients with nodal relapse had a significantly higher risk of distant metastasis on both univariate (p = 0.02) and multivariate analysis (hazard ratio = 4.5, p = 0.006). The 5-year actuarial risk of distant relapse was 29% for patients with neck control versus 81% for patients with neck failure. There was also a trend for decreased survival with nodal relapse. The 5-year actuarial survival was 37% for patients with neck control and 0% for patients with neck relapse. CONCLUSION: The overall incidence of lymph node involvement at diagnosis in patients with maxillary sinus carcinoma was 9%. Following treatment, the 5-year risk of nodal relapse was 12%. SCC histology was associated with a high incidence of initial nodal involvement and nodal relapse. None of the patients presenting with SCC histology and N0 necks had nodal relapse after elective neck irradiation. Patients who had nodal relapse had a higher risk of distant metastasis and poorer survival. Therefore, our present policy is to consider elective neck irradiation in patients with T3-4 SCC of the maxillary sinus.

Postoperative irradiation of minor salivary gland malignancies of the head and neck.

OBJECTIVES: (1) To review the Stanford experience with postoperative radiotherapy for minor salivary gland carcinomas of the head and neck. (2) To identify patterns of failure and prognostic factors for these tumors. MATERIALS AND METHODS: Fifty-four patients with localized tumors were treated with curative intent at Stanford University between 1966 and 1995. The 1992 AJCC staging for squamous cell carcinomas was used to retrospectively stage these patients. Thirteen percent had stage I, 22% stage II, 26% stage III, and 39% stage IV neoplasms. Thirty-two patients (59%) had adenoid cystic carcinoma, 15 (28%) had adenocarcinoma, and seven (13%) had mucoepidermoid carcinoma. Thirty (55%) had positive surgical margins and seven (13%) had cervical lymph node involvement at diagnosis. The median follow-up for alive patients was 7.8 years (range: 25 months-28.9 years). RESULTS: The 5- and 10-year actuarial local control rates were 91 and 88%, respectively. Advanced T-stage (T3-4), involved surgical margins, adenocarcinoma histology, and sinonasal and oropharyngeal primaries were associated with poorer local control. The 5- and 10-year actuarial freedom from distant metastasis were 86 and 81%, respectively. Advanced T-stage (T3-4), lymph node involvement at diagnosis, adenoid cystic and high-grade mucoepidermoid histology were associated with a higher risk of distant metastases. The 10-year cause-specific survival (CSS) and overall survival (OS) were 81 % and 63%, respectively. On multivariate analysis, prognostic factors affecting survival were T-stage (favoring T1-2), and N-stage (favoring NO). When T- and N-stage were combined to form the AJCC stage, the latter became the most significant factor for survival. The 10-year OS was 86% for stage I-II vs. 52% for stage III-IV tumors. Late treatment-related toxicity was low (3/54); most complications were mild and no cranial nerve damage was noted. CONCLUSIONS: Surgical resection and carefully planned post-operative radiation therapy for minor salivary gland tumors is well tolerated and effective with high local control rates. AJCC stage was the most significant predictor for survival and should be used for staging minor salivary gland carcinomas.

In vivo lactate editing with simultaneous detection of choline, creatine, NAA, and lipid singlets at 1.5 T using PRESS excitation with applications to the study of brain and head and neck tumors.

Two T2-independent J-difference lactate editing schemes for the PRESS magnetic resonance spectroscopy localization sequence are introduced. The techniques, which allow for simultaneous acquisition of the lactate doublet (1.3 ppm) and edited singlets upfield of and including choline (3.2 ppm), exploit the dependence of the in-phase intensity of the methyl doublet upon the time interval separating two inversion (BASING) pulses applied to its coupling partner after initial excitation. Editing method 1, which allows for echo times TE = n/J (n = 1, 2, 3, . . . . ), alters the BASING carrier frequency for each of two cycles so that, for one cycle, the quartet is inverted, whereas, for the other cycle, the quartet is unaffected. Method 2, which also provides water suppression, allows for editing for TE > 1/J by alternating, between cycles, the time interval separating the inversion pulses. Experimental results were obtained at 1.5 T using a Shinnar Le-Roux-designed maximum phase inversion pulse with a filter transition bandwidth of 55 Hz. Spectra were acquired from phantoms and in vivo from the human brain and neck. In a neck muscle study, the lipid suppression factor, achieved partly through the use of a novel phase regularization algorithm, was measured to be over 10(3). Spectra acquired from a primary brain and a metastatic neck tumor demonstrated the presence of lactate and choline signals consistent with abnormal spectral patterns. The advantages and limitations of the methods are analyzed theoretically and experimentally, and significance of the results is discussed.

In vivo 1H MR spectroscopy of human head and neck lymph node metastasis and comparison with oxygen tension measurements.

BACKGROUND AND PURPOSE: Current diagnostic methods for head and neck metastasis are limited for monitoring recurrence and assessing oxygenation. 1H MR spectroscopy (1H MRS) provides a noninvasive means of determining the chemical composition of tissue and thus has a unique potential as a method for localizing and characterizing cancer. The purposes of this investigation were to measure 1H spectral intensities of total choline (Cho), creatine (Cr), and lactate (Lac) in vivo in human lymph node metastases of head and neck cancer for comparison with normal muscle tissue and to examine relationships between metabolite signal intensities and tissue oxygenation status. METHODS: Volume-localized Lac-edited MRS at 1.5 T was performed in vivo on the lymph node metastases of 14 patients whose conditions were untreated and who had primary occurrences of squamous cell carcinoma. MRS measurements were acquired also from the neck muscle tissue of six healthy volunteers and a subset of the patients. Peak areas of Cho, Cr, and Lac were calculated. Tissue oxygenation (pO2) within the abnormal lymph nodes was measured independently using an Eppendorf polarographic oxygen electrode. RESULTS: Cho:Cr ratios were significantly higher in the nodes than in muscle tissue (node Cho:Cr = 2.9 +/- 1.6, muscle Cho:Cr = 0.55 +/- 0.21, P = .0006). Lac was significantly higher in cancer tissue than in muscle (P = .01) and, in the nodes, showed a moderately negative correlation with median pO2 (r = -.76) over a range of approximately 0 to 30 mm Hg. Nodes with oxygenation values less than 10 mm Hg had approximately twice the Lac signal intensity as did nodes with oxygenation values greater than 10 mm Hg (P = .01). Cho signal intensity was not well correlated with pO2 (r = -.46) but seemed to decrease at higher oxygenation levels (>20 mm Hg). CONCLUSION: 1H MRS may be useful for differentiating metastatic head and neck cancer from normal muscular tissue and may allow for the possibility of assessing oxygenation. Potential clinical applications include the staging and monitoring of treatment.

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.

Management of the clinically positive neck in organ preservation for advanced head and neck cancer.

BACKGROUND: To investigate clinicopathologic predictive criteria for the optimal management of neck metastases in patients with advanced head and neck cancers treated with combined chemoradiotherapy. METHODS: Prospective study, 48 patients. Mean length follow-up, 23 months. RESULTS: Neck stage predicted neck response to chemoradiotherapy; N3 necks showed more partial responses (P = 0.04), and N1 necks showed more complete responses (P = 0.12). Primary tumor site strongly predicted the pathologic response found on neck dissection in patients with a clinical partial response (cPR) following chemoradiotherapy. There was no difference in survival between patients with a clinical complete response (cCR) after chemoradiotherapy, and patients with a pathologic complete response (pCR) after neck dissection (P = 0.20); however, when grouped together, these patients survived longer than did patients with a pPR at neck dissection (P = 0.06). CONCLUSIONS: Clinical response to induction chemotherapy is a poor predictor of ultimate neck control. Induction chemotherapy followed by chemoradiotherapy, and planned neck dissection for patients with persistent cervical lymphadenopathy, provides good regional control.

Cosmetic enhancement associated with surgery for obstructive sleep apnea.

OBJECTIVE: To document the capacity of surgery for obstructive sleep apnea (OSA) to incorporate techniques that incidentally improve the cosmetic features of the patients. STUDY DESIGN: Retrospective analysis of surgical outcomes at an academic practice. METHODS: Moderate to severe OSA usually requires multilevel pharyngeal surgery, including tongue base surgery. The surgical procedures, including hyoid myotomy and mandibular osteotomy with tongue advancement, afford the opportunity to address cosmetic deficits, such as microgenia and excessive submental skin and fat. Outcomes achieved using these procedures over a 4-year period were analyzed. RESULTS: Of 428 consecutive patients presenting for evaluation of sleep-related breathing disorders, 212 were deemed surgical candidates. Ninety-seven of these had office-based procedures for snoring, upper airway resistance syndrome, or mild OSA. The remaining 115 had formal surgical procedures done, and 68 of these had multilevel pharyngeal surgery. Of these, 12 had defined cosmetic deficiencies that were addressed at the time of the sleep apnea surgery. There were 7 men and 5 women, with a mean age of 48.2 years. The group was moderately obese (mean BMI = 31.8) and had moderate to severe OSA (mean RDI = 37.0, mean LSAT = 78%). Cosmetic deficits identified included turkey gobbler deformity (n = 8), microgenia (n = 6), excessive submental fat (n = 2), and nasal deformity (n = 1); several patients had more than one addressable problem. All patients achieved an improved postoperative appearance. Representative photographs are presented. CONCLUSIONS: A surgical approach to the management of sleep apnea affords an opportunity to also address cosmetic deficiencies, including excessive submental skin and fat, microgenia, and nasal deformities.

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.

Detection of metastases from head and neck cancers.

Before treatment for head and neck malignancies is begun, a search for distant metastases (DM) is performed. The first objective of this review was to determine the accuracy of liver function tests (LFT), alkaline phosphatase (AP) tests, and chest radiographs (CXR) in detection of DM. Second, an effort was made to identify tumor characteristics which are associated with a higher incidence of DM and therefore justify the use of more precise screening tools. An analysis of 97 patients with noncutaneous squamous cell carcinomas presenting to the Stanford Head and Neck Tumor Board in 1991 revealed 17 DM in 14 patients. There were 10 pulmonary metastases, 5 bone metastases, and 2 hepatic metastases. CXR had a sensitivity of 50% and a specificity of 94% for detection of pulmonary DM. AP tests showed a sensitivity of 20% and a specificity of 98% for detection of bone DM. LFT had a sensitivity of 50% and an 81% specificity for demonstration of hepatic DM. A separate analysis of 79 patients with known DM from two hospitals showed the incidence of DM to be increased in patients who had tumors of advanced stage, advanced T status, and poor histologic differentiation and to also be increased in the presence of local-regional recurrence. There was little association of DM with N status. The sensitivity of CXR and laboratory tests, which are currently used in evaluation for DM at most cancer centers, is disappointing; these tests should be viewed as gross screening examinations. We recommend a chest computed tomography scan in the event of an abnormal CXR, a bone scan in the event of an elevated AP, and either an ultrasound or computed tomography/magnetic resonance imaging scan of the liver when elevated LFT levels are present, depending on tumor stage and differentiation.

Cephalometric parameters after multilevel pharyngeal surgery for patients with obstructive sleep apnea.

Cephalometric studies have shown narrowing in the upper airway at multiple levels in patients with obstructive sleep apnea. Uvulopalatopharyngoplasty (UPPP), mandibular osteotomy with genioglossus advancement, and hyoid myotomy with advancement address narrowing in the retropalatal and retrolingual regions. In an effort to relate postoperative clinical changes to anatomic changes, cephalometric studies were performed on 44 patients who underwent multilevel pharyngeal surgery (UPPP, genioglossus advancement, hyoid myotomy with advancement). Both pre- and postoperative radiographs were available for 23 of these patients. The posterior airway space (P = .09), minimal posterior airway space (P = .04), posterior uvular space (P = .06), mandibular plane-to-hyoid distance (MP-H) (P = .06) and central incisor-to-tongue base distance (P = .02) all improved after surgery. None of the measurements of the posterior airway were significantly different between responders and nonresponders. The degree of collapse of the palate on modified Müller maneuver was highly correlated with the severity of sleep apnea as measured by the respiratory disturbance index; the collapse of the lateral pharyngeal walls was moderately correlated; and collapse of the base of tongue was not correlated. Cephalometric radiographs may reflect the anatomic changes that result from upper airway surgery for sleep apnea, but these changes are not useful for assessing surgical efficacy. The modified Müller maneuver, however, may represent a more predictive evaluation.

Trends in the management of alcohol withdrawal syndrome.

Alcohol use among head and neck cancer patients is common. Alcohol withdrawal (especially delirium tremens) poses significant potential morbidity to postsurgical patients. Treatment with newer benzodiazepines (BZDs) such as lorazepam and midazolam has become more widespread, and mortality rates from severe alcohol withdrawal have decreased in recent years. The authors retrospectively studied 102 patients with a diagnosis of alcohol withdrawal, including 20 patients undergoing surgery for cancer of the head and neck. There were 81 men and 21 women, with a mean (+/- standard deviation [SD]) age of 52.3 (+/- 16.1) years. Many of these patients (46%) were treated with more than one BZD or other neuroleptic, while 49% received single agent therapy of either chlordiazepoxide (26%) or lorazepam (23%). Delirium tremens occurred in 12% of all patients undergoing withdrawal and in 10% of head and neck cancer patients, with a mortality rate of 9% and 0%, respectively. Single agent use was successful in greater than 95% when either lorazepam or chlordiazepoxide was used. Instances of combination treatment where older BZDs were used yielded a 69% success rate. The higher complication rate and lower treatment success with combination treatment was multifactorial. Optimal management of the alcohol withdrawal syndrome requires an understanding of its pathophysiology and the principles of its prevention along with a familiarity of BZD pharmacokinetic drug profiles. The authors present a treatment plan which is cost-effective, keeps morbidity low, and should allow a continued decreasing trend in mortality rates from delirium tremens.