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Supplemental Table 1. Criteria for Unresectable Disease Supplemental Table 2. Modified RECIST Criteria for Head and Neck Cancer. Supplemental Table 3. Summary of Serum Analyte Levels. Supplemental Figure 1. Study Schematic Supplemental Figure 2. Time to locoregional failure for all eligible and treated patients (a) and by tumor HPV status (b). Log rank test comparing time to failure for HPV+ versus HPV- p value provided. Supplemental Figure 3. Representative tissue cores with high or low expression levels of XPF or ERCC1 as assessed by AQUA. Tumors were stained for cytokeratin (CK) to create a tumor mask and with DAPI to define the nuclear compartment. Supplemental Figure 4. Representative tumor IHC molecular correlates ERCC1, XPF and MET.

List of Supplemental Materials: Supplemental Table 1. Criteria for Unresectable Disease Supplemental Table 2. Modified RECIST Criteria for Head and Neck Cancer. Supplemental Table 3. Summary of Serum Analyte Levels. Supplemental Figure 1. Study Schematic Supplemental Figure 2. Time to locoregional failure for all eligible and treated patients (a) and by tumor HPV status (b). Log rank test comparing time to failure for HPV+ versus HPV- p value provided. Supplemental Figure 3. Representative tissue cores with high or low expression levels of XPF or ERCC1 as assessed by AQUA. Tumors were stained for cytokeratin (CK) to create a tumor mask and with DAPI to define the nuclear compartment. Supplemental Figure 4. Representative tumor IHC molecular correlates ERCC1, XPF and MET.

Purpose: Treatment with cisplatin or cetuximab combined with radiotherapy each yield superior survival in locally advanced squamous cell head and neck cancer (LA-SCCHN) compared with radiotherapy alone. Eastern Cooperative Oncology Group Trial E3303 evaluated the triple combination.Experimental Design: Patients with stage IV unresectable LA-SCCHN received a loading dose of cetuximab (400 mg/m2) followed by 250 mg/m2/week and cisplatin 75 mg/m2 q 3 weeks ×3 cycles concurrent with standard fractionated radiotherapy. In the absence of disease progression or unacceptable toxicity, patients continued maintenance cetuximab for 6 to 12 months. Primary endpoint was 2-year progression-free survival (PFS). Patient tumor and blood correlates, including tumor human papillomavirus (HPV) status, were evaluated for association with survival.Results: A total of 69 patients were enrolled; 60 proved eligible and received protocol treatment. Oropharyngeal primaries constituted the majority (66.7%), stage T4 48.3% and N2-3 91.7%. Median radiotherapy dose delivered was 70 Gy, 71.6% received all three cycles of cisplatin, and 74.6% received maintenance cetuximab. Median PFS was 19.4 months, 2-year PFS 47% [95% confidence interval (CI), 33%–61%]. Two-year overall survival (OS) was 66% (95% CI, 53%–77%); median OS was not reached. Response rate was 66.7%. Most common grade ≥3 toxicities included mucositis (55%), dysphagia (46%), and neutropenia (26%); one attributable grade 5 toxicity occurred. Only tumor HPV status was significantly associated with survival. HPV was evaluable in 29 tumors; 10 (all oropharyngeal) were HPV positive. HPV+ patients had significantly longer OS and PFS (P = 0.004 and P = 0.036, respectively).Conclusions: Concurrent cetuximab, cisplatin, and radiotherapy were well tolerated and yielded promising 2-year PFS and OS in LA-SCCHN with improved survival for patients with HPV+ tumors. Clin Cancer Res; 20(19); 5041–51. ©2014 AACR.

ImportancePrior investigations in social determinants of health (SDoH) in pediatric head and neck cancer (HNC) have only considered a narrow scope of HNCs, SDoH, and geography while lacking inquiry into the interrelational association of SDoH with disparities in clinical pediatric HNC.ObjectivesTo evaluate the association of SDoH with disparities in HNC among children and adolescents and to assess which specific aspects of SDoH are most associated with disparities in dynamic and regional sociodemographic contexts.Design, Setting, and ParticipantsThis retrospective cohort study included data about patients (aged ≤19 years) with pediatric HNC who were diagnosed from 1975 to 2017 from the Surveillance, Epidemiology, and End Results Program (SEER) database. Data were analyzed from October 2021 to October 2022.ExposuresOverall social vulnerability and its subcomponent contributions from 15 SDoH variables, grouped into socioeconomic status (SES; poverty, unemployment, income level, and high school diploma status), minority and language status (ML; minoritized racial and ethnic group and proficiency with English), household composition (HH; household members aged ≥65 and ≤17 years, disability status, single-parent status), and housing and transportation (HT; multiunit structure, mobile homes, crowding, no vehicle, group quarters). These were ranked and scored across all US counties.Main Outcomes and MeasuresRegression trends were performed in continuous measures of surveillance and survival period and in discrete measures of advanced staging and surgery receipt.ResultsA total of 37 043 patients (20 729 [55.9%] aged 10-19 years; 18 603 [50.2%] male patients; 22 430 [60.6%] White patients) with 30 different HNCs in SEER had significant relative decreases in the surveillance period, ranging from 23.9% for malignant melanomas (mean [SD] duration, lowest vs highest vulnerability: 170 [128] months to 129 [88] months) to 41.9% for non-Hodgkin lymphomas (mean [SD] duration, lowest vs highest vulnerability: 216 [142] months vs 127 [94] months). SES followed by ML and HT vulnerabilities were associated with these overall trends per relative-difference magnitudes (eg, SES for ependymomas and choroid plexus tumors: mean [SD] duration, lowest vs highest vulnerability: 114 [113] months vs 86 [84] months; P P = .43) to 61.4% for gliomas not otherwise specified (NOS) (mean [SD] survival, lowest vs highest vulnerability: 44 [84] months to 17 [28] months; P P Conclusions and RelevanceIn this cohort study of patients with pediatric HNC, significant decreases in receipt of care and survival time were observed with increasing SDoH vulnerability.

Reconstruction of head and neck defects is a delicate endeavor that poses numerous intrinsic and extrinsic challenges, which are currently magnified by rising health care costs and limitations in system resources. Current trends in the United States heavily favor the use of free tissue transfer over locoregional pedicles flaps (LRPF); however, the latter group is often undervalued, offering high utility, practicality, and cost-efficiency whilst providing equivalent results. The submental island flap and supraclavicular artery island flap are two LRPF that should be in the arsenal of the modern reconstructive surgeon.

BACKGROUND The National Quality Forum has endorsed quality-improvement measures for multiple cancer types that are being developed into actionable tools to improve cancer care. No nationally endorsed quality metrics currently exist for head and neck cancer. METHODS The authors identified patients with surgically treated, invasive, head and neck squamous cell carcinoma in the National Cancer Data Base from 2004 to 2014 and compared the rate of adherence to 5 different quality metrics and whether compliance with these quality metrics impacted overall survival. The metrics examined included negative surgical margins, neck dissection lymph node (LN) yield ≥ 18, appropriate adjuvant radiation, appropriate adjuvant chemoradiation, adjuvant therapy within 6 weeks, as well as overall quality. RESULTS In total, 76,853 eligible patients were identified. There was substantial variability in patient-level adherence, which was 80% for negative surgical margins, 73.1% for neck dissection LN yield, 69% for adjuvant radiation, 42.6% for adjuvant chemoradiation, and 44.5% for adjuvant therapy within 6 weeks. Risk-adjusted Cox proportional-hazard models indicated that all metrics were associated with a reduced risk of death: negative margins (hazard ratio [HR] 0.73; 95% confidence interval [CI], 0.71-0.76), LN yield ≥ 18 (HR, 0.93; 95% CI, 0.89-0.96), adjuvant radiation (HR, 0.67; 95% CI, 0.64-0.70), adjuvant chemoradiation (HR, 0.84; 95% CI, 0.79-0.88), and adjuvant therapy ≤6 weeks (HR, 0.92; 95% CI, 0.89-0.96). Patients who received high-quality care had a 19% reduced adjusted hazard of mortality (HR, 0.81; 95% CI, 0.79-0.83). CONCLUSIONS Five head and neck cancer quality metrics were identified that have substantial variability in adherence and meaningfully impact overall survival. These metrics are appropriate candidates for national adoption. Cancer 2017. © 2017 American Cancer Society.

An otherwise healthy 24-year-old man presented with 1 week of fever, facial pain and swelling. He initially sought care at an outside hospital, where he was diagnosed with folliculitis and sent home with oral antibiotics. On arrival at our institution, CT neck was ordered, which demonstrated diffuse submental phlegmon, prompting incision and drainage. After initial improvement, the patient experienced high fevers and increased swelling just 12 hours later. The decision was made to take the patient for operative exploration, and wide debridement was performed due to suspicion for necrotising fasciitis intraoperatively that was ultimately confirmed on final pathology. Final speciation of intraoperative culture demonstrated a clindamycin-resistant and methicillin-resistant strain of Staphylococcus aureus. The patient was managed with intravenous antibiotics, additional debridement and careful wound care. Delayed partial closure of wound was eventually performed once patient showed marked and persistent clinical improvement. The patient was discharged on hospital day 12 with close follow-up.

Importance Venous thromboembolism (VTE), which includes deep venous thrombosis or pulmonary embolism, is the number 1 cause of preventable death in surgical patients. Current guidelines from the American College of Chest Physicians provide VTE prevention recommendations that are specific to individual surgical subspecialties; however, no guidelines exist for otolaryngology. Objective To examine the rate of VTE for various otolaryngology procedures compared with an established average-risk field (general surgery) and low-risk field (plastic surgery). Design, Setting, and Participants This cohort study compared the rate of VTE after different otolaryngology procedures with those of general and plastic surgery in the American College of Surgeons National Surgical Quality Improvement Program from January 1, 2005, through December 31, 2013. We used univariate and multivariable logistic regression analysis of clinical characteristics, cancer status, and Caprini score to compare different risk stratification of patients. Data analysis was performed from May 1, 2016, to April 1, 2017. Exposure Surgery. Main Outcomes and Measures Thirty-day rate of VTE. Results A total of 1 295 291 patients, including 31 896 otolaryngology patients (mean [SD] age, 53.9 [16.7] years; 14 260 [44.7%] male; 21 603 [67.7%] white), 27 280 plastic surgery patients (mean [SD] age, 50.5 [13.9] years; 4835 [17.7%] male; 17 983 [65.9%] white), and 1 236 115 general surgery patients (mean [SD] age, 54.9 [17.2] years; 484 985 [39.2%] male; 867 913 [70.2%] white) were compared. The overall 30-day rate of VTE was 0.5% for otolaryngology compared with 0.7% for plastic surgery and 1.2% for general surgery. We identified a high-risk group for VTE in otolaryngology (n = 3625) that included free or regional tissue transfer, laryngectomy, composite resection, skull base surgery, and incision and drainage. High-risk otolaryngology patients experienced similar rates of VTE as general surgery patients across all Caprini risk levels. Low-risk otolaryngology patients (n = 28 271) experienced lower rates of VTE than plastic surgery patients across all Caprini risk levels. Malignant tumors were associated with VTE; however, the rates varied by cancer type and were 11-fold greater for cancers of the upper aerodigestive tract compared with thyroid cancers (odds ratio, 10.97; 95% CI, 7.38-16.31). Venous thromboembolism was associated with a 14-fold higher 30-day mortality among otolaryngology patients (5.1% mortality with VTE vs 0.4% mortality without VTE; difference, 4.7%; 95% CI of the difference, 2.2%-9.3%). Conclusions and Relevance Most patients undergoing otolaryngology procedures are at low risk of VTE, indicating that guidelines for a low-risk population could be adapted to otolaryngology. Patients undergoing high-risk otolaryngology procedures should be considered as candidates for more aggressive VTE prophylaxis.

Importance Free flap reconstruction of the head and neck is routinely performed with success rates around 94% to 99% at most institutions. Despite experience and meticulous technique, there is a small but recognized risk of partial or total flap loss in the postoperative setting. Historically, most microvascular surgeons involve resident house staff in flap monitoring protocols, and programs relied heavily on in-house resident physicians to assure timely intervention for compromised flaps. In 2003, the Accreditation Council for Graduate Medical Education mandated the reduction in the hours a resident could work within a given week. At many institutions this new era of restricted resident duty hours reshaped the protocols used for flap monitoring to adapt to a system with reduced resident labor. Objectives To characterize various techniques and frequencies of free flap monitoring by nurses and resident physicians; and to determine if adapted resident monitoring frequency is associated with flap compromise and outcome. Design, Setting, and Participants This multi-institutional retrospective review included patients undergoing free flap reconstruction to the head and/or neck between January 2005 and January 2015. Consecutive patients were included from different academic institutions or tertiary referral centers to reflect evolving practices. Main Outcomes and Measures Technique, frequency, and personnel for flap monitoring; flap complications; and flap success. Results Overall, 1085 patients (343 women [32%] and 742 men [78%]) from 9 institutions were included. Most patients were placed in the intensive care unit postoperatively (n = 790 [73%]), while the remaining were placed in intermediate care (n = 201 [19%]) or in the surgical ward (n = 94 [7%]). Nurses monitored flaps every hour (q1h) for all patients. Frequency of resident monitoring varied, with 635 patients monitored every 4 hours (q4h), 146 monitored every 8 hours (q8h), and 304 monitored every 12 hours (q12h). Monitoring techniques included physical examination (n = 949 [87%]), handheld external Doppler sonography (n = 739 [68%]), implanted Doppler sonography (n = 333 [31%]), and needle stick (n = 349 [32%]); 105 patients (10%) demonstrated flap compromise, prompting return to the operating room in 96 patients. Of these 96 patients, 46 had complete flap salvage, 22 had partial loss, and 37 had complete loss. The frequency of resident flap checks did not affect the total flap loss rate (q4h, 25 patients [4%]; q8h, 8 patients [6%]; and q12h, 8 patients [3%]). Flap salvage rates for compromised flaps were not statistically different. Conclusions and Relevance Academic centers rely primarily on q1h flap checks by intensive care unit nurses using physical examination and Doppler sonography. Reduced resident monitoring frequency did not alter flap salvage nor flap outcome. These findings suggest that institutions may successfully monitor free flaps with decreased resident burden.

An otherwise healthy 24-year-old man presented with 1 week of fever, facial pain and swelling. He initially sought care at an outside hospital, where he was diagnosed with folliculitis and sent home with oral antibiotics. On arrival at our institution, CT neck was ordered, which demonstrated diffuse submental phlegmon, prompting incision and drainage. After initial improvement, the patient experienced high fevers and increased swelling just 12 hours later. The decision was made to take the patient for operative exploration, and wide debridement was performed due to suspicion for necrotising fasciitis intraoperatively that was ultimately confirmed on final pathology. Final speciation of intraoperative culture demonstrated a clindamycin-resistant and methicillin-resistant strain of Staphylococcus aureus. The patient was managed with intravenous antibiotics, additional debridement and careful wound care. Delayed partial closure of wound was eventually performed once patient showed marked and persistent clinical improvement. The patient was discharged on hospital day 12 with close follow-up.

Purpose: Treatment with cisplatin or cetuximab combined with radiotherapy each yield superior survival in locally advanced squamous cell head and neck cancer (LA-SCCHN) compared with radiotherapy alone. Eastern Cooperative Oncology Group Trial E3303 evaluated the triple combination. Experimental Design: Patients with stage IV unresectable LA-SCCHN received a loading dose of cetuximab (400 mg/m2) followed by 250 mg/m2/week and cisplatin 75 mg/m2 q 3 weeks ×3 cycles concurrent with standard fractionated radiotherapy. In the absence of disease progression or unacceptable toxicity, patients continued maintenance cetuximab for 6 to 12 months. Primary endpoint was 2-year progression-free survival (PFS). Patient tumor and blood correlates, including tumor human papillomavirus (HPV) status, were evaluated for association with survival. Results: A total of 69 patients were enrolled; 60 proved eligible and received protocol treatment. Oropharyngeal primaries constituted the majority (66.7%), stage T4 48.3% and N2-3 91.7%. Median radiotherapy dose delivered was 70 Gy, 71.6% received all three cycles of cisplatin, and 74.6% received maintenance cetuximab. Median PFS was 19.4 months, 2-year PFS 47% [95% confidence interval (CI), 33%–61%]. Two-year overall survival (OS) was 66% (95% CI, 53%–77%); median OS was not reached. Response rate was 66.7%. Most common grade ≥3 toxicities included mucositis (55%), dysphagia (46%), and neutropenia (26%); one attributable grade 5 toxicity occurred. Only tumor HPV status was significantly associated with survival. HPV was evaluable in 29 tumors; 10 (all oropharyngeal) were HPV positive. HPV+ patients had significantly longer OS and PFS (P = 0.004 and P = 0.036, respectively). Conclusions: Concurrent cetuximab, cisplatin, and radiotherapy were well tolerated and yielded promising 2-year PFS and OS in LA-SCCHN with improved survival for patients with HPV+ tumors. Clin Cancer Res; 20(19); 5041–51. ©2014 AACR.

No consensus exists as to the best technique, or techniques, to optimize wound healing, decrease pharyngocutaneous fistula formation, and shorten both hospital length of stay and time to initiation of oral intake after salvage laryngectomy. We sought to combine the recent experience of multiple high-volume institutions, with different reconstructive preferences, in the management of pharyngeal closure technique for post-radiation therapy salvage total laryngectomy in an effort to bring clarity to this clinical challenge.To determine if the use of vascularized flaps in either an onlay or interposed fashion reduces the incidence or duration of pharyngocutaneous fistula after salvage laryngectomy compared with simple primary closure of the pharynx.Multi-institutional retrospective review of all patients undergoing total laryngectomy after having received definitive radiation therapy with or without chemotherapy between January 2005 and January 2012, conducted at 7 academic medical centers.Academic, tertiary referral centers.The study population comprised 359 patients from 8 institutions. All patients had a history of laryngeal irradiation and underwent laryngectomy between 2005 and 2012. They were grouped as primary closure, pectoralis myofascial onlay flap, or interposed free tissue. All patients had a minimum of 4 months follow-up.Fistula incidence, severity, and predictors of fistula.Of the 359 patients, fistula occurred in 94 (27%). For patients with fistula, hospital stay increased from 8.9 to 12.1 days (P.001) and oral diet initiation was delayed from 10.5 days to 29.9 days (P.001). Patients were grouped according to closure technique: primary closure (n = 99), pectoralis onlay flap (n = 40), and interposed free tissue (n = 220). Incidence of fistula with primary closure was 34%. For the interposed free flap group, the fistula rate was lower at 25% (P = .07). Incidence of fistula was the lowest for the pectoralis onlay group at 15% (P = .02). Multivariate analysis confirmed a significantly lower fistula rate with either flap technique. For patients who developed fistula, mean duration of fistula was significantly prolonged with primary closure (14.0 weeks) compared with pectoralis flap (9.0 weeks) and free flap (6.5 weeks).Pharyngocutaneous fistula remains a significant problem following salvage laryngectomy. Use of nonirradiated, vascularized flaps reduced the incidence and duration of fistula and should be considered during salvage laryngectomy.

Importance Airway management during microvascular reconstruction of the upper aerodigestive tract is of utmost importance; however, there is considerable debate about optimal management of the airway. Objective To examine if free tissue transfer to the upper aerodigestive tract without tracheotomy was associated with an increased rate of airway complications or death. Design, Setting, and Participants Cohort study of 861 patients undergoing microvascular reconstruction to sites in the oral cavity, oropharynx (excluding the base of tongue), and nasal and/or sinus cavity using data from the American College of Surgeons National Surgical Quality Improvement Program from 2005 to 2013. We compared the rate of airway-specific complications of patients who underwent simultaneous tracheotomy vs those who did not undergo tracheotomy. Exposure Tracheotomy. Main Outcomes and Measures The 30-day rate of airway-specific complications, including unplanned intubation, prolonged mechanical ventilation, or death. Results Among the 861 patients included in this study (mean age 61 years and 63.3% male), 551 underwent tracheotomy and 310 did not undergo tracheotomy. The rate of tracheotomy based on anatomic site was 66.1% for oral cavity (n = 728), 40.5% for nasal/sinus cavity (n = 85), and 70.3% for oropharynx (n = 48). The difference in the overall rate of airway complications between patients in the no-tracheotomy (10.3%) and tracheotomy (8.3%) groups was 2.0% (95% CI, 1.9%-6.4%). There were no significant differences in the rate of airway complications in the no-tracheotomy and tracheotomy groups for death (0.3% vs 0.7%, respectively; difference, 0.3%; 95% CI, −2.0% to 3.2%), unplanned intubation (3.2% vs 2.9%, respectively; difference, 0.3%; 95% CI, −2.0% to 3.2%) or for prolonged mechanical ventilation (8.1% vs 7.3%; difference, 0.8%; 95% CI, −2.7% to 4.8%). On multivariate analysis tracheotomy was not associated with the primary outcome (odds ratio [OR], 0.8; 95% CI, 0.5-1.3); however, preoperative bleeding disorder (OR, 9.0; 95% CI, 3.3-24.4), preoperative dyspnea (OR, 2.9; 95% CI, 1.5-5.5), and resection of the floor of mouth (OR, 2.1; 95% CI, 1.1-3.9) were associated with airway complications or death. Conclusions and Relevance Free tissue transfer to the upper aerodigestive tract is frequently performed without tracheotomy, and this is not associated with a significantly increased rate of airway complications. Routine tracheotomy may be safely avoided in a subset of patients undergoing microvascular reconstruction of the upper aerodigestive tract.

The optimal reconstruction of total glossectomy defects with or without total laryngectomy is controversial. Various pedicled and free tissue flaps have been advocated, but long-term data on functional outcomes are not available to date.To compare various total glossectomy defect reconstructive techniques used by multiple institutions and to identify factors that may lead to improved long-term speech and swallowing function.A multi-institutional, retrospective review of electronic medical records of patients undergoing total glossectomy at 8 participating institutions between June 1, 2001, and June 30, 2011, who had a minimal survival of 2 years.Total glossectomy with or without total laryngectomy.Demographic and surgical factors were compiled and correlated with speech and swallowing outcomes.At the time of the last follow-up, 45% (25 of 55) of patients did not have a gastrostomy tube, and 76% (42 of 55) retained the ability to verbally communicate. Overall, 75% (41 of 55) of patients were tolerating at least minimal nutritional oral intake. Feeding tube dependence was not associated with laryngeal preservation or the reconstructive techniques used, including flap suspension, flap innervation, or type of flap used. Laryngeal preservation was associated with favorable speech outcomes, such as the retained ability to verbally communicate in 97% of those not undergoing total laryngectomy (35 of 36 patients) vs 44% (7 of 16) in those undergoing total laryngectomy (P .001), as well as those not undergoing total laryngectomy achieving some or all intelligible speech in 85% (29 of 34 patients) compared with 31% (4 of 13) undergoing total laryngectomy achieving the same intelligibility (P .001).In patients with total glossectomy, feeding tube dependence was not associated with laryngeal preservation or the reconstructive technique, including flap innervation and type of flap used. Laryngeal preservation was associated with favorable speech outcomes such as the retained ability to verbally communicate and higher levels of speech intelligibility.

Objective To assess relative benefit of combined radiotherapy and surgery over single-modality treatment for advanced-stage squamous cell carcinoma of the aerodigestive tract by means of several multivariable analyses to control for patient variables. Design Medical chart review. Setting University medical center. Patients and Methods The study included 532 patients receiving initial therapy between January 1, 1980, and December 31, 1989. Three multivariate techniques (multiple logistic regression, propensity score stratification, and conjunctive consolidation) were used to compare outcomes for treatment groups. Main Outcome Measure Five-year survival. Results Survival for radiation, surgery, and combined treatment groups were 24%, 40%, and 46%, respectively. With the use of multiple logistic regression to control patient variables, the radiation group had a significantly lower survival than the combined therapy group (risk ratio, 2.24; 95% confidence interval, 1.32-3.80), while there was no statistical difference for the surgery group compared with the combined therapy group (risk ratio, 1.26; 95% confidence interval, 0.78-2.03). When analyzed by propensity score, 5-year survival was higher in each quintile for the combined therapy group than for the group who received radiation alone (P= .002). There was no significant difference in survival between the surgery and combined treatment groups (P= .25). Conjunctive consolidation was used to create a clinical staging system to compare outcomes across treatment groups. In each clinical severity stage, radiation alone had a lower survival than combined therapy (P= .001), while no statistical difference was noted between surgery and combined therapy (P= .50). Conclusions All 3 statistical techniques showed a significantly lower survival for patients treated with radiation alone vs combined therapy. No significant difference was noted between surgery and combined therapy. Propensity score analysis and conjunctive consolidation are useful techniques to control prognostic variables in cancer database studies and should be used in future outcome studies that address more current treatment dilemmas in head and neck oncology.

Summary Eur. J. Cell Biol. 81, 26–35 (2002). Upon request of the auhtors the name of Pierre Jurdic (Laboratoire de Biologie Moleculaire et Cellulaire, UMR 5665 CNRS/ENS, INRA, Ecole Normale Superieure de Lyon, Lyon/France) has to be added to the list of authors between J. B. Levy and W. C. Horne.