Very low dose bevacizumab for the treatment of epistaxis in patients with hereditary hemorrhagic telangiectasia.

Hereditary hemorrhagic telangiectasia (HHT) is a disease characterized by mucocutaneous telangiectasias and visceral arteriovenous malformations. The genetic mutations that cause this disease result in elevated levels of vascular endothelial growth factor, which is inhibited by bevacizumab. Previous studies have shown bevacizumab treatment to be effective in reducing symptoms, but study protocols have all used oncological dosing parameters, which carry several well-described serious side effects. This study investigates whether drastically lower dosages of bevacizumab than normally used in oncological treatment could control epistaxis in patients with HHT and medically refractory epistaxis. A prospective, open-label, noncomparative study enrolled six patients receiving 0.125-mg/kg infusions of bevacizumab once every 4 weeks for a total of six infusions. Severity of epistaxis was assessed with the epistaxis severity score, and quality-of-life measures were followed with the 20-item Sino-Nasal Outcome Test and 36-item Short Form surveys. A statistically significant improvement was seen in the control of epistaxis severity and frequency, with minimal negative side effects and high patient satisfaction. Very low dose bevacizumab treatment is an effective method of controlling medically refractory epistaxis in patients with HHT and additional investigation to optimize dosing guidelines is warranted.

The Young's procedure for severe epistaxis from hereditary hemorrhagic telangiectasia.

BACKGROUND: Surgical treatment of epistaxis in hereditary hemorrhagic telangiectasia (HHT) has historically been managed with the laser procedure or the septodermoplasty procedure. For transfusion-dependent patients with severe epistaxis we have been performing the Young's procedure or surgical closure of the nostrils. The objective of this study was to report treatment of severe epistaxis related to HHT with the Young's procedure and assess patient outcome. METHODS: Patients with severe iron or blood transfusion-dependent epistaxis who underwent a Young's procedure in three otolaryngology HHT centers were reviewed. Patients were evaluated for postoperative epistaxis and subjective outcome. RESULTS: Forty-three patients underwent a Young's procedure for severe epistaxis and were observed for a mean of 34 months. The procedure was well tolerated by all patients and 30 of 36 patients (83%) experienced complete cessation of bleeding after the Young's procedure. Patients had a mean increase in hemoglobin of 4.68 g/dL after the procedure. The average Glasgow Benefit Inventory score after surgery was 43.56. No patients requested a reversal of the procedure. CONCLUSION: The Young's procedure is a safe and efficacious procedure with complete cessation of epistaxis in most patients with severe epistaxis and HHT.

From virtual reality to the operating room: the endoscopic sinus surgery simulator experiment.

OBJECTIVE: Establish the feasibility of a predictive validity study in sinus surgery simulation training and demonstrate the effectiveness of the Endoscopic Sinus Surgery Simulator (ES3) as a training device. STUDY DESIGN: Prospective, multi-institutional controlled trial. SETTING: Four tertiary academic centers with accredited otolaryngology-head and neck surgery residency programs. SUBJECTS: Twelve ES3-trained novice residents were compared with 13 control novice residents. METHODS: Subjects were assessed on the performance of basic sinus surgery tasks. Their first in vivo procedure was video recorded and submitted to a blinded panel of independent experts after the panel established a minimum inter-rater reliability of 80 percent. The recordings were reviewed by using a standardized computer-assisted method and customized metrics. Results were analyzed with the Mann-Whitney U test. Internal rater consistency was verified with Pearson moment correlation. RESULTS: Completion time was significantly shorter in the experimental group (injection P = 0.003, dissection P < 0.001), which, according to the rater panel, also demonstrated higher confidence (P = 0.009), demonstrated skill during instrument manipulation (P = 0.011), and made fewer technical mistakes during the injection task (P = 0.048) compared with the control group. The raters' post hoc internal consistency was deemed adequate (r > 0.5 between serial measurements). CONCLUSION: The validity of the ES3 as an effective surgical trainer was verified in multiple instances, including those not depending on subjective rater evaluations. The ES3 is one of the few virtual reality simulators with a comprehensive validation record. Advanced simulation technologies need more rapid implementation in otolaryngology training, as they present noteworthy potential for high-quality surgical education while meeting the necessity of patient safety.

Confirmation of no causal relationship between tracheotomy and aspiration status: a direct replication study.

Debate continues regarding an association between tracheotomy and aspiration status. The aim of this research was to perform a direct replication study to investigate further the causal relationship, if any, between tracheotomy and aspiration. Twenty-five consecutive adult hospitalized patients participated. Inclusion criteria were a pretracheotomy dysphagia evaluation, subsequent tracheotomy and tracheotomy tube placement, then a post-tracheotomy dysphagia reevaluation prior to decannulation. Twenty-two (88%) participants exhibited the same aspiration status or resolved aspiration pre- versus post-tracheotomy. Three participants exhibited new aspiration post-tracheotomy due to worsening medical conditions. Conversely, four participants exhibited resolved aspiration post-tracheotomy due to improved medical conditions. Excluding these seven participants, all nine participants who aspirated pretracheotomy also aspirated post-tracheotomy and all nine participants who did not aspirate pretracheotomy also did not aspirate post-tracheotomy (P > 0.05). No statistically significant differences were found between aspiration status and days since tracheotomy (chi (2) = 0.08, P > 0.05) or between age and aspiration status (P > 0.05). The absence of a causal relationship between tracheotomy and aspiration status was confirmed.

A prognostic index for predicting lymph node metastasis in minor salivary gland cancer.

PURPOSE: Large studies examining the clinical and pathological factors associated with nodal metastasis in minor salivary gland cancer are lacking in the literature. METHODS AND MATERIALS: Using the Surveillance, Epidemiology, and End Results (SEER) database, we identified 2,667 minor salivary gland cancers with known lymph node status from 1988 to 2004. Univariate and multivariate analyses were conducted to identify factors associated with the use of neck dissection, the use of external beam radiation therapy, and the presence of cervical lymph node metastases. RESULTS: Four hundred twenty-six (16.0%) patients had neck nodal involvement. Factors associated with neck nodal involvement on univariate analysis included increasing age, male sex, increasing tumor size, high tumor grade, T3-T4 stage, adenocarcinoma or mucoepidermoid carcinomas, and pharyngeal site of primary malignancy. On multivariate analysis, four statistically significant factors were identified, including male sex, T3-T4 stage, pharyngeal site of primary malignancy, and high-grade adenocarcinoma or high-grade mucoepidermoid carcinomas. The proportions (and 95% confidence intervals) of patients with lymph node involvement for those with 0, 1, 2, 3, and 4 of these prognostic factors were 0.02 (0.01-0.03), 0.09 (0.07-0.11), 0.17 (0.14-0.21), 0.41 (0.33-0.49), and 0.70 (0.54-0.85), respectively. Grade was a significant predictor of metastasis for adenocarcinoma and mucoepidermoid carcinoma but not for adenoid cystic carcinoma. CONCLUSIONS: A prognostic index using the four clinicopathological factors listed here can effectively differentiate patients into risk groups of nodal metastasis. The precision of this index is subject to the limitations of SEER data and should be validated in further clinical studies.

End-to-side venous anastomosis with an anastomotic coupling device for microvascular free-tissue transfer in head and neck reconstruction.

OBJECTIVE: The purpose of this study is to demonstrate the success rate of using a coupling device for end-to-side venous anastomosis in patients undergoing free-tissue transfer (FTT) in head and neck reconstruction. METHODS AND MEASURES: Retrospective data were collected in consecutive series of 134 patients undergoing surgical resection of head and neck tumors followed by FTT. All microvascular FTTs were performed at Yale-New Haven Hospital between November 2001 and August 2007. The Unilink coupling device was used to perform arterial and venous anastomosis in this case series. Flap survival and thrombosis of the venous anastomoses were determined. RESULTS: One hundred thirty-four consecutive patients underwent a total of 137 microvascular FTTs using a coupling device. In our series, a total of 173 end-to-side anastomoses were completed in 96 patients. Of these, 77 patients had both venous anastomoses, 17 underwent one end-to-side and one end-to-end anastomoses, and two patients had one venous anastomosis per patient performed in end-to-side fashion. Reconstruction included 76 radial forearm, 17 fibula, and three rectus abdominis free flaps. There were three vascular insufficiency related complications of which two were salvageable. There was one case of flap failure (1%), resulting in a free flap survival rate of 99%. CONCLUSION: This largest reported series of end-to-side venous anastomoses with an anastomotic coupling device demonstrates feasibility and efficacy of this technique in head and neck reconstruction.

Capillary blood gas: a novel means of assessing free flap perfusion in an animal model.

OBJECTIVE: To demonstrate that in comparison to implantable O(2) microelectrodes, capillary blood gas measurements represent a reliable, accessible, and easy method of identifying failing free flaps. STUDY DESIGN: Groin fasciocutaneous flaps were elevated in 10 rats and following venous occlusion, O(2) microelectrode measurements (pO(2) and flow), and capillary blood gas measurements (pO(2), pCO(2), pH, HCO(3)) were obtained at 10-minute intervals. RESULTS: Measurements with capillary blood gas paralleled measurements with O(2) microelectrodes. Average capillary blood gas pO(2) fell from 42.71 to 31.57 mm Hg at 10 minutes and then to 28.67 mm Hg at 20 minutes. Average pH fell from 7.38 to 7.33 at 10 minutes and to 7.30 at 20 minutes. Results were statistically significant with both the paired Student's t test and the Wilcoxon signed rank test. CONCLUSION: While providing users an ability to simultaneously monitor accepted modalities of flap surveillance, pH and pO(2), capillary blood gas is a reliable, accessible, and reproducible marker of flap health.

Long-term complications of septal dermoplasty in patients with hereditary hemorrhagic telangiectasia.

OBJECTIVE: Septal dermoplasty has been recommended as the treatment of choice for life-threatening epistaxis in patients with hereditary hemorrhagic telangiectasia. This study evaluates the complications of septal dermoplasty in the management of transfusion-dependent epistaxis. STUDY DESIGN: Consecutive retrospective study. SUBJECTS AND METHODS: Between 1994 and 2006, septal dermoplasty was performed on 106 consecutive patients with transfusion dependent epistaxis. Of 103 potential patients, 37 either died or were lost to follow-up, which left 66 patients for study. Data on complications and quality of life were collected on 50 (76%) of 66 patients (mean follow-up, 3.75 years) via phone interview. RESULTS: Seventy-eight percent experienced nasal odor; 72% had nasal crusting; 58% had decreased sense of smell; 30% noted worsened sinus infection; 88% could breathe through their nose; 86% stated improved quality of life. CONCLUSION: Septal dermoplasty remains an effective way of treating transfusion dependent epistaxis in patients with hereditary hemorrhagic telangiectasia and subjectively improves their quality of life.

Arterial coupling for microvascular free tissue transfer.

OBJECTIVE: The purpose of this study was to demonstrate the efficacy of arterial coupling. STUDY DESIGN: Retrospective data were collected in a consecutive series of 124 patients undergoing surgical resection of head and neck tumors followed by free tissue transfer (FTT). METHODS AND MEASURES: The Unilink coupling device was used to perform arterial and venous anastomosis. Flap survival and thrombosis of the arterial anastomoses were determined. RESULTS: A total of 124 consecutive patients underwent a total of 127 microvascular FTTs. Reconstruction included 90 radial forearm, 26 fibula, 9 rectus abdominis, and 2 iliac crest myocutaneous free flaps. There were four (3.2%) complications related to arterial insufficiency in our series, three of which were salvageable. There were three (2.4%) flap failures, resulting in an overall free flap survival rate of 97.6 percent. CONCLUSION: The flap survival with the Unilink Microvascular Anastomotic System is similar to that of standard suture techniques. Use of a coupler device is the preferred method in performing microvascular FTT at our institution.

Investigation of tracheoesophageal voice prosthesis leakage patterns: patient's self-report versus clinician's confirmation.

BACKGROUND: This study investigated the patient's self-report and clinician's confirmation of tracheoesophageal voice prosthesis leakage patterns (through or around) with or without the cough reflex and whether prosthesis diameter affected the leakage route. METHODS: Sixty-six consecutive participants with a total of 200 patient-initiated reasons for prosthesis changes were enrolled prospectively. Patient's self-report of leakage and cough reflex were recorded prior to clinician's confirmation. RESULTS: One-hundred eight (54%) of the 200 patient-initiated reasons for prosthesis changes were leakage through or around the voice prosthesis. Leakage was unrecognized in 21 (23%) of 92 instances, even though 15 (71%) of those 21 instances exhibited a cough reflex. Clinician's confirmed leakage in 118 (59%) of 200 patient-initiated reasons for prosthesis changes. Coughing occurred significantly less with leakage around (9 [53%] of 17 instances) than that with leakage through the voice prosthesis (80 [88%] of 91 instances) (chi(2) [1, N=108], p< .05). Leakage around the voice prosthesis occurred more with 20-Fr diameter prostheses (16 [76%] of 21 instances). CONCLUSIONS: Patient education is important for reliable identification of leakage for prompt prosthesis replacement. Leakage around the voice prosthesis can be minimized or avoided by initially fitting and continuing the use of smaller diameter (16 Fr) voice prostheses.

Septectomy and septal dermoplasty for the treatment of severe transfusion-dependent epistaxis in patients with hereditary hemorrhagic telangiectasia and septal perforation.

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterized by abnormal angiogenesis with resultant telangiectasia formation in mucocutaneous tissues, visceral organs, and the central nervous system. The most common manifestation of HHT is epistaxis resulting from trauma to thin-walled telangiectasias. Many patients with HHT experience worsened epistaxis due to the presence of a septal perforation. Septal perforation in HHT patients results from aggressive noncartilage sparing treatments such as monopolar cauterization. Although the mainstay of treatment for patients with severe transfusion-dependent HHT remains to be septal dermoplasty (SD), patients with a septal perforation are less likely to have a successful outcome. In this small subset of patients, septectomy (ST) combined with SD is proposed to eliminate this variable to improve skin graft uptake and therefore outcome. This study reviews the indications, procedure, and outcome of nine patients with severe transfusion-dependent HHT and septal perforation who underwent the combined procedure of SD/ST. METHODS: Nine HHT patients with severe transfusion-dependent epistaxis and septal perforation underwent SD/ST at our institution over a 5-year period. Quality of life, including number of daily events of epistaxis, and transfusion requirements were determined before and after surgery. Technical aspects of the procedure as well as complications were reviewed. RESULTS: The combined procedure of SD/ST resulted in a long-lasting subjective improvement in quality of life for all patients. Similarly, transfusion requirements were reduced from 22.61 to 9.57 (p < 0.05). There were no complications or increased morbidity from the procedure. CONCLUSION: Combined SD/ST is a safe and effective treatment for HHT patients with transfusion-dependent epistaxis and septal perforation.

Construct validity of the endoscopic sinus surgery simulator: II. Assessment of discriminant validity and expert benchmarking.

OBJECTIVES: To establish discriminant validity of the endoscopic sinus surgery simulator (ES3) (Lockheed Martin, Akron, Ohio) between various health care provider experience levels and to define benchmarking criteria for skills assessment. DESIGN: Prospective multi-institutional comparison study. SETTING: University-based tertiary care institution. PARTICIPANTS: Ten expert otolaryngologists, 14 otolaryngology residents, and 10 medical students. INTERVENTIONS: Subjects completed the ES3's virtual reality curriculum (10 novice mode, 10 intermediate mode, and 3 advanced mode trials). Performance scores were recorded on each trial. Performance differences were analyzed using analysis of variance for repeated measures (experience level as between-subjects factor). MAIN OUTCOME MEASURES: Simulator performance scores, accuracy, time to completion, and hazard disruption. RESULTS: The novice mode accurately distinguished the 3 groups, particularly at the onset of training (mean scores: senior otolaryngologists, 66.0; residents, 42.7; students, 18.3; for the paired comparisons between groups 1 and 2 and groups 1 and 3, P = .04 and .03, respectively). Subjects were not distinguished beyond trial 5. The intermediate mode only discriminated students from other subjects (P = .008). The advanced mode did not show performance differences between groups. Scores on the novice mode predicted those on the intermediate mode, which predicted advanced mode scores (r = 0.687), but no relationship was found between novice and advanced scores. All groups performed equally well and with comparable consistency at the outset of training. Expert scores were used to define benchmark criteria of optimal performance. CONCLUSIONS: This study completes the construct validity assessment of the ES3 by demonstrating its discriminant capabilities. It establishes expert surgeon benchmark performance criteria and shows that the ES3 can train novice subjects to attain those. The refined analysis of trial performance scores could serve educational and skills assessment purposes. Current studies are evaluating the transfer of surgical skills acquired on the ES3 to the operating room (predictive validity).

Postoperative concurrent chemoradiotherapy with mitomycin in advanced squamous cell carcinoma of the head and neck: results from three prospective randomized trials.

UNLABELLED: Recent prospective randomized trials have shown concurrent chemoradiotherapy improves locoregional control in postoperative patients with squamous cell carcinoma of the head and neck using cisplatin-based regimes. This report presents data pooled from three randomized trials employing mitomycin, selecting those patients treated postoperatively, to evaluate the long-term benefit of mitomycin in the postoperative setting and to compare these results with those of two other recently published randomized trials. METHODS AND MATERIALS: Between 1980 and 1999, a total of 331 patients with squamous cell carcinoma of the head and neck from the three prospective trials were enrolled. Of the 205 postoperative patients in these trials, 103 were randomized to receive mitomycin and radiation, while 102 received radiation alone or radiation with porfiromycin in the third trial. Patients were treated with standard daily radiotherapy to a total median dose of 60 Gy over 47 days. Patients who were randomized to mitomycin C received 15 mg/m2 of the drug on days 5 and 47 (or last day). RESULTS: The 5-year rate of locoregional control was higher in the mitomycin arms. There was no statistically significant difference in the rates of overall survival or distant metastasis. Patients had a lower percentage of high-risk factors in both arms of the study, compared with patients in the large prospective trials, including positive margins, two or more positive lymph nodes, or oropharynx primary tumors. The gains in locoregional control realized with mitomycin were similar to the improvements in the recently published randomized trials using platinum. CONCLUSIONS: These results confirm significant gains in locoregional control using concurrent chemoradiotherapy in the postoperative setting for patients with squamous cell carcinoma of the head and neck. The lack of consensus over a benefit in the rates of overall survival and distant metastasis emphasizes the need for further prospective trials in the postoperative management of squamous cell carcinoma of the head and neck.

Arterial coupling for microvascular free tissue transfer in head and neck reconstruction.

OBJECTIVE: To demonstrate the efficacy of arterial coupling. DESIGN: We report our experience in head and neck reconstruction with the Unilink Microvascular Anastomotic System (Synovis MCA, Birmingham, Ala). Data were collected in a consecutive series of 49 patients undergoing composite resection of head and neck tumors followed by free tissue transfer. SETTING: All patient care took place at Yale-New Haven Hospital, New Haven, Conn, a university-based tertiary care facility. PATIENTS: Forty-nine consecutive patients aged 43 to 85 years underwent a total of 50 microvascular free tissue transfers using the Unilink coupling device. There were 18 women and 31 men, and the following 3 types of flaps were performed: radial forearm (n = 36), fibula (n = 12), and rectus abdominus (n = 2). INTERVENTIONS: The Unilink coupling device was used in this case series. Each arterial and venous anastomosis was performed with the coupling device. Free tissue transfers were monitored clinically and outcomes were recorded. MAIN OUTCOME MEASURES: Flap survival and thrombosis of the arterial anastomoses were determined, as was median length of stay. RESULTS: There were no flap failures in the series. Of the 50 coupled arterial anastomoses, the predominant coupler size used was 2.5 mm in diameter. Reconstructions included 36 radial forearm, 12 fibular osteocutaneous, and 2 rectus abdominus myocutaneous free flaps. One intraoperative arterial thrombosis occurred, requiring hand-sewn anastomosis, and another pulled away from the intact coupler in a steroid-dependent patient. There were no complications related to technical performance of the coupling device. The median length of stay was 14 days. CONCLUSION: While hand-sewn anastomoses in free tissue transfer remain the preferred technique for many microsurgeons, use of the coupler is a viable alternative to sutured anastomoses.

Incidence of vocal fold immobility in patients with dysphagia.

This study prospectively investigated the incidence of vocal fold immobility, unilateral and bilateral, and its influence on aspiration status in a referred population of 1452 patients for a dysphagia evaluation from a large, urban, tertiary-care, teaching hospital. Main outcome measures included overall incidence of vocal fold immobility and aspiration status, with specific emphasis on age, etiology, and side of vocal fold immobility, i.e., right, left, or bilateral. Overall incidence of vocal fold immobility was 5.6% (81 of 1452 patients), including 47 males (mean age 55.7 yr) and 34 females (mean age 59.7 yr). In the subgroup of patients with vocal fold immobility, 31% (25 of 81) exhibited unilateral right, 60% (49 of 81) unilateral left, and 9% (7 of 81) bilateral impairment. Overall incidence of aspiration was found to be 29% (426 of 1452) of all patients referred for a swallow evaluation. Aspiration was observed in 44% (36 of 81) of patients presenting with vocal fold immobility, i.e., 44% (11 of 25) unilateral right, 43% (21 of 49) unilateral left, and 57% (4 of 7) bilateral vocal fold immobility. Left vocal fold immobility occurred most frequently due to surgical trauma. A liquid bolus was aspirated more often than a puree bolus. Side of vocal fold immobility and age were not factors that increased incidence of aspiration. In conclusion, vocal fold immobility, with an incidence of 5.6%, is not an uncommon finding in patients referred for a dysphagia evaluation in the acute-care setting, and vocal fold immobility, when present, was associated with a 15% increased incidence of aspiration when compared with a population already being evaluated for dysphagia.

Presence of a tracheotomy tube and aspiration status in early, postsurgical head and neck cancer patients.

BACKGROUND: We sought to investigate the effects, if any, that the presence of a tracheotomy tube has on aspiration status in early, postsurgical head and neck cancer patients. METHODS: Twenty-two consecutive adult, postoperative head and neck cancer patients were prospectively evaluated with fiberoptic endoscopic evaluation of swallowing (FEES) under three conditions: (1) tracheotomy tube present, (2) tracheotomy tube removed and tracheostoma covered with gauze sponge; and (3) tracheotomy tube removed and tracheostoma left open and uncovered. For each condition, the endoscope was first inserted transnasally to determine aspiration status during FEES and then inserted through the tracheostoma to corroborate aspiration status by examining the distal trachea inferiorly to the carina. Three experienced examiners determined aspiration status under each condition and endoscope placement. RESULTS: There was 100% agreement on aspiration status between FEES results and endoscopic examination through the tracheostoma. Specifically, 13 of 22 patients (59%) swallowed successfully and nine of 22 (41%) aspirated. There was also 100% agreement on aspiration status for tracheotomy tube present, decannulation and tracheostoma covered by gauze sponge, and decannulation and tracheostoma left open and uncovered. CONCLUSIONS: Neither presence of a tracheotomy tube nor decannulation affected aspiration status in early, postsurgical head and neck cancer patients. The clinical impressions that a tracheotomy or tracheotomy tube increases aspiration risk or that decannulation results in improved swallowing function are not supported. Rather, need for a tracheotomy indicates comorbidities (eg, respiratory failure, trauma, stroke, advanced age, reduced functional reserve, and medications used to treat the critically ill) that by themselves predispose patients for dysphagia and aspiration.

Interventional neuroradiology adjuncts and alternatives in patients with head and neck vascular lesions.

Vascular lesions of the head and neck can result from a variety of neoplastic and traumatic conditions that may cause local neurologic symptoms or may compromise the carotid or vertebral arteries, leading to ischemic deficits. Management of lesions involving vascular structures at the skull base may require a temporary balloon occlusion tolerance test or endovascular transarterial embolization as part of the preoperative management. Endovascular techniques can also be used as a salvage measure for severe head and neck bleeding and can assist with the management of vascular injury occurring in the operative or perioperative setting. Familiarity with the role of endovascular techniques in this group of patients may favorably influence patient management and outcome.

The role of RANTES in nasal polyposis.

BACKGROUND: Characteristic infiltrates of eosinophils are a hallmark of nasal polyps (NPs). Several studies suggest that members of the CC chemokine family may be involved in this process. RANTES (regulated on activation, normal t-cell-expressed and secreted) is a member of the CC chemokine family with chemotactic activity on mainly eosinophils and T lymphocytes. Thus, RANTES is an interesting target for the recruitment of eosinophils and T lymphocytes into the nose. The degree of the tissue eosinophilia has been reported to correlate with the severeness of the symptomatology of the disease and the extension on the lower respiratory tract, as well as with the probability of the recurrence of NPs. Therefore, we hypothesized that high numbers of eosinophils correlate with high levels of RANTES and that associated atopic diseases modify this correlation. METHODS: Total RNA was extracted from NP homogenates, reverse transcribed and RANTES mRNA expression analyzed using semiquantitative reverse transcription polymerase chain reaction and Northern blot analysis. Histological studies divided NPs in an eosinophilic and low eosinophilic group. Additionally, RANTES protein concentration was measured in homogenates by a RANTES-specific enzyme-linked immunosorbent assay. RESULTS: This study has clearly shown that RANTES is expressed and secreted in NPs. The group with a high tissue eosinophilia had a significant higher RANTES gene expression and protein production than NPs without tissue eosinophilia. The isolated coincidence of acetylsalicyl acid intolerance with chronic hyperplastic sinusitis/NP additionally increased significantly the RANTES amounts in NPs. CONCLUSION: Increased RANTES leads to increased tissue eosinophilia. Associated acetylsalicylic acid intolerance seems to enhance the amount of RANTES in NPs and might explain in part the more severe clinical course in those patients. Thus, RANTES appears to play an important role in mobilization of eosinophils into the local inflamed tissue.

Concurrent chemo-radiotherapy with mitomycin C compared with porfiromycin in squamous cell cancer of the head and neck: final results of a randomized clinical trial.

PURPOSE: Previous randomized trials have shown a benefit with concurrent use of the hypoxic cell cytotoxin mitomycin C (MC) and radiation (RT) in the management of squamous cell cancer of the head and neck (SCCHN). We conducted a randomized trial comparing MC with porfiromycin (POR) in combination with RT in the management of SCCHN. METHODS AND MATERIALS: Between 1992 and 1999, 128 patients with SCCHN were enrolled in this prospective randomized trial. Patients were stratified by management intent, and balanced with respect to stage and site of disease. They were randomized to receive MC (15 mg/M(2)) or POR (40 mg/M(2)) on Days 5 and 47 (or last day) of RT. Of 121 evaluable patients, 61 were randomized to MC and 60 to POR. Patients were treated with standard daily RT to a total median dose of 64 Gy over 47 days. Patients were well balanced with respect to management intent, stage, site, age, sex, hemoglobin levels, tumor grade, radiation dose, and days on treatment. RESULTS: There were no significant differences between the two arms with respect to acute hematologic or nonhematologic toxicities. As of January 2003 with a median follow-up of 6.3 years, there have been 19 local relapses (4 MC vs. 15 POR), 21 regional relapses (7 MC vs. 14 POR), 24 distant metastases (11 MC vs. 13 POR), and 66 deaths (33 MC vs. 33 POR). MC was superior to POR with respect to 5-year local relapse-free survival (91.6% vs. 72.7%, p = 0.01), local-regional relapse-free survival (82% vs. 65.3%, p = 0.05), and disease-free survival (72.8% vs. 52.9%, p = 0.026). There were no significant differences between the two arms with respect to overall survival (49.2% vs. 54.4%) or distant metastasis-free rate (79.9% vs. 75.9%). CONCLUSIONS: Despite promising preclinical data, and an acceptable toxicity profile, POR was inferior to MC as an adjunct to RT in the management of SCCHN. This randomized trial emphasizes the need for randomized studies to evaluate new agents in the management of SCCHN.

Microsurgical free flap reconstruction outcomes in head and neck cancer patients after surgical extirpation and intraoperative brachytherapy.

OBJECTIVES: The management of recurrent or persistent head and neck cancer poses a challenging problem. Salvage surgery for these individuals consists of ablative surgery, interstitial brachytherapy, and microsurgical free flap reconstruction. This study reviews complications after such reconstruction. METHODS: We reviewed 139 consecutive head and neck cancer patients undergoing free flap reconstruction from January 1994 to May 2002. These included 66 patients with recurrent head and neck cancer undergoing intraoperative brachytherapy (IOBT) and free flap reconstruction and 73 undergoing free flap reconstructions only. A total of 142 reconstructions were performed, with three patients in IOBT group receiving two free flap reconstructions per patient, giving us a total of 69 reconstructions in the IOBT group versus 73 in the non-IOBT group. Nine patients were excluded from the IOBT group because of nonsynchronous use of brachytherapy and reconstruction, and 10 patients were excluded from the other group because they had prior radiotherapy or surgical treatment, leaving us with a total of 123 reconstructions, 60 in the IOBT group and 63 in the non-IOBT group. The IOBT group patients received iodine Vicryl seed implants, palladium seed implants, or both, to deliver an average dose of 79.3 +/- 31.8 Gy (mean +/- 1SD) to the surgical bed. RESULTS: All patients were followed for evidence of local wound complications. The IOBT group showed multiple complications in 23 (38.33%) of 60 reconstructions, the most common being wound dehiscence in 11. This, when compared with the non-IOBT group complications (15.87%), was found to be statistically significant (chi test, P <.01). CONCLUSION: IOBT increases the rate of complications in patients undergoing microvascular free tissue transfer. This, however, should not deter or alter the aggressiveness of cancer therapy used for managing recurrent head and neck cancer.