Bio

Clinical Focus


  • Otolaryngology
  • Cancer > Head and Neck Cancer

Academic Appointments


Administrative Appointments


  • Member, Stanford Cancer Institute (2013 - Present)
  • Head and Neck Clinical Care Program Leader, Stanford Cancer Center (2013 - Present)

Professional Education


  • Fellowship:MD Anderson Cancer Center (2003) TX
  • Board Certification: Otolaryngology, American Board of Otolaryngology (2002)
  • Residency:Baylor College of Medicine (2001) TX
  • Internship:Baylor College of Medicine (1996) TX
  • Medical Education:Vanderbilt University School of Medicine (1995) TN
  • Fulbright Scholarship, Université de Paris V, Rene Descartes Sorbonne Paris Cité, France, Post-doctoral Fellowship in Head and Neck Surgery (2003)
  • Fellowship, Department of Head and Neck Surgery, The University of Texas M.D. Anderson Cancer Center, Head and Neck Surgical Oncology (2003)
  • Residency, Bobby R. Alford Department of Otolaryngology--Head and Neck Surgery, Baylor College of Medicine, Otolaryngology--Head and Neck Surgery (2001)
  • Internship, Debakey Department of Surgery Baylor College of Medicine, General Surgery (1997)
  • MD, Vanderbilt University School of Medicine (1995)

Research & Scholarship

Current Research and Scholarly Interests


Dr. Holsinger’s surgical practice focuses on the surgical management of benign and malignant diseases of the thyroid, parathyroid and head and neck.

His areas of clinical interest include endoscopic head and neck surgery, including robotic thyroidectomy, transoral robotic surgery and transoral laser microsurgery, as well as time-honoured approaches of conservation laryngeal surgery, supracricoid partial laryngectomy.

Publications

Journal Articles


  • Lateral pharyngotomy for selected invasive squamous cell carcinoma of the lateral oropharynx. Part II: When and why. Laryngoscope Laccourreye, O., Benito, J., Garcia, D., Menard, M., Bonfils, P., Holsinger, C. 2013; 123 (11): 2718-2722

    Abstract

    OBJECTIVES/HYPOTHESIS: To analyze local failure following lateral pharyngotomy for selected untreated invasive squamous cell carcinoma (SCC) of the lateral oropharynx. STUDY DESIGN: Retrospective review from a university teaching hospital. METHODS: Inception cohort of 91 patients who underwent lateral pharyngotomy for an isolated and previously untreated selected invasive carcinoma of the lateral oropharynx classified as T1 (26), T2 (47), T3 (11), and T4 (7). Induction chemotherapy, neck dissection, and postoperative radiation therapy were used in 91.2%, 94.5%, and 53.5% of patients. RESULTS: The 5-year Kaplan-Meier estimate of local failure was 16.6% for T1, 19% for T2, 38.6% for T3, and 16.7% for T4 lesions (P = .46). In a logistic regression model, only positive margins of resection statistically increased (P = .01) the risk for local failure. In patients with safe margins of resection, the 5-year Kaplan-Meier estimate of local failure was 5.6% for T1 lesions, 10.7% for T2 lesions, 23.8% for T3 lesions, and 20% for T4 lesions (P = .4). Local failure had a significant impact on increased nodal failure (P = .001) and on reduced survival (P < .0001). CONCLUSION: The lateral pharyngotomy approach should be viewed as a valuable oncologic alternative to both mandibulotomy and chemoradiation in patients with selected SCC of the lateral oropharynx. LEVEL OF EVIDENCE: 4. Laryngoscope, 2013.

    View details for DOI 10.1002/lary.24246

    View details for PubMedID 23775844

  • Lateral Pharyngotomy for Selected Invasive Squamous Cell Carcinoma of the Lateral Oropharynx-Part I: How LARYNGOSCOPE Laccourreye, O., Benito, J., Menard, M., Garcia, D., Malinvaud, D., Holsinger, C. 2013; 123 (11): 2712-2717

    View details for DOI 10.1002/lary.24161

    View details for Web of Science ID 000326231200034

  • Conventional transoral surgery for stage III squamous cell carcinoma of the tonsillar region HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK Laccourreye, O., Malinvaud, D., Alzahrani, H., Menard, M., Garcia, D., Bonfils, P., Holsinger, F. C. 2013; 35 (5): 653-659

    Abstract

    The purpose of this study was to review the results of conventional transoral resection and neck dissection for stage I to II squamous carcinoma of the tonsillar region.We conducted a retrospective review of 65 patients (stage I, 21 patients; stage II, 44 patients). Induction chemotherapy and postoperative radiation therapy (RT) were administered in 76.9% and 12.3%, respectively, of these cases.The postoperative course was uneventful in 96.9% of patients. Five-year actuarial estimates for local recurrence, nodal recurrence, distant metastasis, and survival were 0% to 7.6%, 0% to 7.8%, 0% to 7.3%, and 70.8% to 71.5% for patients with T1 to T2 carcinoma, respectively. Contralateral and retropharyngeal recurrence occurred in only 1 patient.Conventional transoral resection with ipsilateral neck dissection provides an alternative approach for patients with stage I to II squamous cell carcinoma (SCC) of the tonsillar region. A primary surgical approach spares the use of radiotherapy to eliminate late effects and to permit its use for subsequent management of metachronous head and neck second primary cancer.

    View details for DOI 10.1002/hed.23018

    View details for Web of Science ID 000317304000014

    View details for PubMedID 22605677

  • Robot-Assisted Selective Neck Dissection of Levels II to V via a Modified Facelift or Retroauricular Approach OTOLARYNGOLOGY-HEAD AND NECK SURGERY Park, Y. M., Holsinger, F. C., Kim, W. S., Park, S. C., Lee, E. J., Choi, E. C., Koh, Y. W. 2013; 148 (5): 778-785

    Abstract

    We performed robot-assisted selective neck dissection via a modified facelift or retroauricular approach without creating an apparent scar around the neck to remove neck node of levels II to V after transoral robotic surgery of a primary lesion in patients with laryngopharyngeal carcinoma. Patient data were prospectively analyzed to verify the feasibility and efficacy of robot-assisted neck dissection in the treatment of cN0 laryngopharyngeal carcinoma.Prospective case series.University tertiary care facility.Between March 2011 and March 2012, 7 patients were enrolled in the study. Before study initiation, the Institutional Review Board of Yonsei University approved the protocol, and informed consent was obtained from all patients.Robot-assisted neck dissection was successfully performed in all patients. Five patients underwent selective neck dissection including levels II to IV, and 2 patients underwent selective neck dissection including levels II to V. The average number of lymph nodes retrieved was 25.1. Occult nodal metastasis was found in 1 (14%) neck specimen. During the follow-up period (mean of 13.5 months), all patients were alive without locoregional recurrence. All patients were extremely satisfied with their cosmetic results.Robot-assisted selective neck dissection is a feasible and safe technique to manage the neck in cN0 laryngopharyngeal carcinoma patients. It may be especially helpful for patients undergoing transoral robotic surgery since no apparent scar around the neck remains. Long-term results with respect to oncologic safety and functional outcomes are required to establish the validity of robot-assisted neck dissection.

    View details for DOI 10.1177/0194599813478934

    View details for Web of Science ID 000318363500011

    View details for PubMedID 23429040

  • Biomarker-Directed Therapy of Squamous Carcinomas of the Head and Neck: Targeting PI3K/PTEN/mTOR Pathway JOURNAL OF CLINICAL ONCOLOGY Holsinger, F. C., Piha-Paul, S. A., Janku, F., Hong, D. S., Atkins, J. T., Tsimberidou, A. M., Kurzrock, R. 2013; 31 (9): E137-E140

    View details for DOI 10.1200/JCO.2012.43.2716

    View details for Web of Science ID 000316187600006

    View details for PubMedID 23358976

  • A 13-Gene Signature Prognostic of HPV-Negative OSCC: Discovery and External Validation CLINICAL CANCER RESEARCH Lohavanichbutr, P., Mendez, E., Holsinger, F. C., Rue, T. C., Zhang, Y., Houck, J., Upton, M. P., Futran, N., Schwartz, S. M., Wang, P., Chen, C. 2013; 19 (5): 1197-1203

    Abstract

    To identify a prognostic gene signature for patients with human papilloma virus (HPV)-negative oral squamous cell carcinomas (OSCC).Two gene expression datasets were used: a training dataset from the Fred Hutchinson Cancer Research Center (FHCRC, Seattle, WA; n = 97) and a validation dataset from the MD Anderson Cancer Center (MDACC, Houston, TX; n = 71). We applied L1/L2-penalized Cox regression models to the FHCRC data on the 131-gene signature previously identified to be prognostic in patients with OSCCs to identify a prognostic model specific for patients with high-risk HPV-negative OSCCs. The models were tested with the MDACC dataset using a receiver operating characteristic (ROC) analysis.A 13-gene model was identified as the best predictor of HPV-negative OSCC-specific survival in the training dataset. The risk score for each patient in the validation dataset was calculated from this model and dichotomized at the median. The estimated 2-year mortality (± SE) of patients with high-risk scores was 47.1% (± 9.24%) compared with 6.35% (± 4.42) for patients with low-risk scores. ROC analyses showed that the areas under the curve for the age, gender, and treatment modality-adjusted models with risk score [0.78; 95% confidence interval (CI), 0.74-0.86] and risk score plus tumor stage (0.79; 95% CI, 0.75-0.87) were substantially higher than for the model with tumor stage (0.54; 95% CI, 0.48-0.62).We identified and validated a 13-gene signature that is considerably better than tumor stage in predicting survival of patients with HPV-negative OSCCs. Further evaluation of this gene signature as a prognostic marker in other populations of patients with HPV-negative OSCC is warranted.

    View details for DOI 10.1158/1078-0432.CCR-12-2647

    View details for Web of Science ID 000315740200027

    View details for PubMedID 23319825

  • Endoscopic supraomohyoid neck dissection via a retroauricular or modified facelift approach: Preliminary results. Head & neck Byeon, H. K., Holsinger, F. C., Koh, Y. W., Ban, M. J., Ha, J. G., Park, J. J., Kim, D., Choi, E. C. 2013

    Abstract

    BACKGROUND: Based on our previous experiences with endoscopic or robotic neck surgery utilizing the retroauricular (RA) or modified facelift (MFL) approach, we realized the value of verifying the feasibility of endoscopic supraomohyoid neck dissection (SOND). Therefore, the purpose of this study was to evaluate the potential role of endoscopic SOND. METHODS: Six patients who underwent elective endoscopic SOND of the ipsilateral neck for biopsy proven head and neck cancer from January 2011 to February 2012 were analyzed. RESULTS: All endoscopic operations via RA or MFL were successfully performed without any significant intraoperative complications or conversion to open surgery. Based on patient-reported outcome questionnaires, all patients were satisfied with the cosmetic surgical outcomes. CONCLUSION: Endoscopic selective neck dissection via an RA or an MFL approach is technically feasible and safe with satisfactory cosmetic results for patients with clinically node-negative early-stage head and neck cancer. © 2013 Wiley Periodicals, Inc. Head Neck, 2013.

    View details for PubMedID 23728878

  • Long-term functional and survival outcomes after induction chemotherapy and risk-based definitive therapy for locally advanced squamous cell carcinoma of the head and neck. Head & neck Hutcheson, K. A., Lewin, J. S., Holsinger, F. C., Steinhaus, G., Lisec, A., Barringer, D. A., Lin, H. Y., Villalobos, S., Garden, A. S., Papadimitrakopoulou, V., Kies, M. S. 2013

    Abstract

    BACKGROUND: The purpose of this study was to evaluate long-term outcomes after induction chemotherapy followed by "risk-based" local therapy for locally-advanced squamous cell carcinoma of the head and neck (SCCHN). METHODS: Forty-seven patients (stage IV; ?N2b) were enrolled in a phase II trial. Baseline and 24-month functional measures included modified barium swallow (MBS) studies, oropharyngeal swallow efficiency (OPSE), and the MD Anderson Dysphagia Inventory (MDADI). Functional status was assessed at 5 years. RESULTS: Five-year overall survival (OS) was 89% (95% confidence interval [CI], 81% to 99%). A nonsignificant 13% average reduction in swallowing efficiency (OPSE) was observed at 24 months relative to baseline (p = .191). MDADI scores approximated baseline at 24 months. Among 42 long-term survivors (median, 5.9 years), 3 patients (7.1%) had chronic dysphagia. The rate of final gastrostomy dependence was 4.8% (2 of 42). CONCLUSION: Sequential chemoradiotherapy achieved favorable outcomes among patients with locally advanced SCCHN, mainly of oropharyngeal origin. MBS and MDADI scores found modest swallowing deterioration at 2 years, and chronic aspiration was uncommon in long-term survivors. © 2013 Wiley Periodicals, Inc. Head Neck, 2013.

    View details for PubMedID 23780650

  • Transoral resection of pharyngeal cancer: Summary of a National Cancer Institute Head and Neck Cancer Steering Committee Clinical Trials Planning Meeting, November 6-7, 2011, Arlington, Virginia HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK Adelstein, D. J., Ridge, J. A., Brizel, D. M., Holsinger, F. C., Haughey, B. H., O'Sullivan, B., Genden, E. M., Beitler, J. J., Weinstein, G. S., Quon, H., Chepeha, D. B., Ferris, R. L., Weber, R. S., Movsas, B., Waldron, J., Lowe, V., Ramsey, S., Manola, J., Yueh, B., Carey, T. E., Bekelman, J. E., Konski, A. A., Moore, E., Forastiere, A., Schuller, D. E., Lynn, J., Ullmann, C. D. 2012; 34 (12): 1681-1703

    Abstract

    Recent advances now permit resection of many pharyngeal tumors through the open mouth, an approach that can greatly reduce the morbidity of surgical exposure. These transoral techniques are being rapidly adopted by the surgical community and hold considerable promise. On November 6-7, 2011, the National Cancer Institute sponsored a Clinical Trials Planning Meeting to address how to further investigate the use of transoral surgery, both in the good prognosis human papillomavirus (HPV)-initiated oropharyngeal cancers, and in those with HPV-unrelated disease. The proceedings of this meeting are summarized.

    View details for DOI 10.1002/hed.23136

    View details for Web of Science ID 000311291900001

    View details for PubMedID 23015475

  • Late dysphagia after radiotherapy-based treatment of head and neck cancer CANCER Hutcheson, K. A., Lewin, J. S., Barringer, D. A., Lisec, A., Gunn, G. B., Moore, M. W., Holsinger, F. C. 2012; 118 (23): 5793-5799

    Abstract

    Changing trends in head and neck cancer (HNC) merit an understanding of the late effects of therapy, but few studies examine dysphagia beyond 2 years of treatment.A case series was examined to describe the pathophysiology and outcomes in dysphagic HNC survivors referred for modified barium swallow (MBS) studies ? 5 years after definitive radiotherapy or chemoradiotherapy (January 2001 through May 2011). Functional measures included the penetration-aspiration scale (PAS), performance status scale-head and neck (PSS-HN), National Institutes of Health Swallowing Safety Scale (NIH-SSS), and MBS impairment profile (MBSImp).Twenty-nine patients previously treated with radiotherapy (38%) or chemoradiotherapy (62%) were included (median years posttreatment, 9; range, 5-19). The majority (86%) had oropharyngeal cancer; 52% were never-smokers. Seventy-five percent had T2 or T3 tumors; 52% were N+. The median age at diagnosis was 55 (range, 38-72). Abnormal late examination findings included: dysarthria/dysphonia (76%), cranial neuropathy (48%), trismus (38%), and radionecrosis (10%). MBS studies confirmed pharyngeal residue and aspiration in all dysphagic cases owing to physiologic impairment (median PAS, 8; median NIH-SSS, 10; median MBSImp, 18), whereas stricture was confirmed endoscopically in 7 (24%). Twenty-five (86%) developed pneumonia, half requiring hospitalization. Swallow postures/strategies helped 69% of cases, but no patient achieved durable improvement across functional measures at last follow-up. Ultimately, 19 (66%) were gastrostomy-dependent.Although functional organ preservation is commonly achieved, severe dysphagia represents a challenging late effect that may develop or progress years after radiation-based therapy for HNC. These data suggest that novel approaches are needed to minimize and better address this complication that is commonly refractory to many standard dysphagia therapies.

    View details for DOI 10.1002/cncr.27631

    View details for Web of Science ID 000311306000010

    View details for PubMedID 23640737

  • Oropharynx Cancer CURRENT PROBLEMS IN CANCER Skinner, H. D., Holsinger, F. C., Beadle, B. M. 2012; 36 (6): 334-415
  • Functional and Oncological Outcomes of Primary Versus Salvage Transoral Laser Microsurgery for Supraglottic Carcinoma ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY Hutcheson, K. A., Jantharapattana, K., Barringer, D. A., Lewin, J. S., Holsinger, F. C. 2012; 121 (10): 664-670

    Abstract

    We evaluated the functional and oncological outcomes of transoral laser microsurgery (TLM) in patients with previously untreated supraglottic carcinoma compared with the outcomes in salvage cases after radiation-based treatment.We conducted a retrospective case-control study at a single academic tertiary care institution. The functional outcomes were stratified by prior irradiation and were assessed at baseline, less than 1 week after operation, and at last follow-up.Five patients underwent TLM for previously untreated disease, and 5 previously irradiated patients underwent salvage TLM for local failure. No patient required tracheostomy. There was no local recurrence after TLM as primary therapy, and none of those patients required radiotherapy. One salvage patient developed local recurrence. The duration of feeding tube dependence (p = 0.049) and the rates of chronic aspiration (more than 1 month after operation; p = 0.048) were significantly higher in the salvage TLM cases than in the previously untreated cases. The median scores on the PSS-HN Understandability of Speech were 75 ("usually understandable") in the salvage group and 100 ("always understandable") in the previously untreated group.Both local control and function were better in the previously untreated patients than in the salvage patients. Our findings provide support for the use of TLM as a primary treatment modality for selected supraglottic carcinomas, but also suggest a potential for functional recovery in both previously untreated and salvage cases.

    View details for Web of Science ID 000310110500008

    View details for PubMedID 23130541

  • Gene Expression in Uninvolved Oral Mucosa of OSCC Patients Facilitates Identification of Markers Predictive of OSCC Outcomes PLOS ONE Lohavanichbutr, P., Houck, J., Doody, D. R., Wang, P., Mendez, E., Futran, N., Upton, M. P., Holsinger, F. C., Schwartz, S. M., Chen, C. 2012; 7 (9)

    Abstract

    Oral and oropharyngeal squamous cell carcinomas (OSCC) are among the most common cancers worldwide, with approximately 60% 5-yr survival rate. To identify potential markers for disease progression, we used Affymetrix U133 plus 2.0 arrays to examine the gene expression profiles of 167 primary tumor samples from OSCC patients, 58 uninvolved oral mucosae from OSCC patients and 45 normal oral mucosae from patients without oral cancer, all enrolled at one of the three University of Washington-affiliated medical centers between 2003 to 2008. We found 2,596 probe sets differentially expressed between 167 tumor samples and 45 normal samples. Among 2,596 probe sets, 71 were significantly and consistently up- or down-regulated in the comparison between normal samples and uninvolved oral samples and between uninvolved oral samples and tumor samples. Cox regression analyses showed that 20 of the 71 probe sets were significantly associated with progression-free survival. The risk score for each patient was calculated from coefficients of a Cox model incorporating these 20 probe sets. The hazard ratio (HR) associated with each unit change in the risk score adjusting for age, gender, tumor stage, and high-risk HPV status was 2.7 (95% CI: 2.0-3.8, p = 8.8E-10). The risk scores in an independent dataset of 74 OSCC patients from the MD Anderson Cancer Center was also significantly associated with progression-free survival independent of age, gender, and tumor stage (HR 1.6, 95% CI: 1.1-2.2, p = 0.008). Gene Set Enrichment Analysis showed that the most prominent biological pathway represented by the 71 probe sets was the Integrin cell surface interactions pathway. In conclusion, we identified 71 probe sets in which dysregulation occurred in both uninvolved oral mucosal and cancer samples. Dysregulation of 20 of the 71 probe sets was associated with progression-free survival and was validated in an independent dataset.

    View details for DOI 10.1371/journal.pone.0046575

    View details for Web of Science ID 000309973900186

    View details for PubMedID 23029552

  • Trade-Off Between Survival and Laryngeal Preservation in Advanced Laryngeal Cancer: The Otorhinolaryngology Patient's Perspective ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY Laccourreye, O., Malinvaud, D., Holsinger, F. C., Consoli, S., Menard, M., Bonfils, P. 2012; 121 (9): 570-575

    Abstract

    We performed a prospective study to evaluate, from the patient's perspective, the trade-off between speech and survival that individuals face when given a diagnosis of advanced-stage laryngeal cancer amenable to either total laryngectomy or a laryngeal preservation protocol using chemotherapy and radiotherapy.Volunteers (309) consecutively seen at the otorhinolaryngology clinic of a university teaching hospital in France completed an anonymous questionnaire designed to determine their position if they faced the diagnosis of an advanced-stage laryngeal cancer. Univariate analysis was performed for potential statistical relationships with various variables.We found that 12.9% of patients were unable to determine their position regarding the two treatment options offered, and this group had a significant statistical relationship with four variables (age, education, professional status, and history of cancer among relatives). We found that 24.6% of patients made survival their main consideration and would not consider any trade-off. Among the 62.5% who considered the trade-off, the percentage of cure that patients were ready to lose in order to preserve their larynx varied from 5% to 100% (mean, 33%; SD, 23%). Aside from the undecided group, none of the variables analyzed was related either to the decision as to whether to consider a trade-off or to the percentage of c re that patients agreed to trade to preserve their larynx.In patients with advanced-stage laryngeal cancer, treatment should be initiated only after careful evaluation of the patient's attitude toward both laryngeal preservation and survival.

    View details for Web of Science ID 000308851800002

    View details for PubMedID 23012894

  • Reconstruction after Robotic Head and Neck Surgery: When and Why JOURNAL OF RECONSTRUCTIVE MICROSURGERY Longfield, E. A., Holsinger, F. C., Selber, J. C. 2012; 28 (7): 445-449

    Abstract

    The advancement of robotically assisted surgery during the last decade has seen a revolution in the approach to surgical oncologic resection, moving toward reducing patient morbidity without compromising oncologic outcomes. In no field has this been more dramatic than in the application of transoral robotic surgery (TORS), using the da Vinci surgical system for resecting tumors of the head and neck. This organ-preserving technique allows the surgeon to remove tumors of the upper aerodigestive tract without external incisions and potentially spare the patient adjuvant treatment. The introduction of TORS improves upon current transoral techniques to the oropharynx and supraglottis. The traditional conception of TORS is that it would be used for smaller tumors and defects would be permitted to heal by secondary intention; however, as head and neck surgeons pursue larger tumors robotically, robotic-assisted reconstruction has entered the paradigm. Given the relative infancy of these procedures, clear guidelines for when reconstruction is warranted do not exist. The current literature, thus far, has focused on feasibility, safety, and implement of the robot in reconstruction. We reviewed the current literature pertinent to TORS reconstruction focusing on patient selection, tumor size, and location. Furthermore, we briefly review our own experience of 20 TORS procedures involving robotic-assisted reconstructions. Finally, we provide an algorithmic approach to determining the need for reconstruction in a given patient. This focuses on four key criteria: tumor location, tumor extent, prior treatment, and patient-specific factors.

    View details for DOI 10.1055/s-0032-1306376

    View details for Web of Science ID 000307630200003

    View details for PubMedID 22399257

  • Robotic Harvest of the Latissimus Dorsi Muscle: Laboratory and Clinical Experience JOURNAL OF RECONSTRUCTIVE MICROSURGERY Selber, J. C., Baumann, D. P., Holsinger, C. F. 2012; 28 (7): 457-464

    Abstract

    Minimally invasive harvest of the latissimus dorsi (LD) muscle is a desirable goal because of both the wide utility of this muscle and the length of incision required to harvest it. In this study, robotic harvest of the LD muscle was evaluated in a cadaver model and clinical series. Ten LD flaps were robotically harvested in eight cadavers. Positioning, port placement, procedural steps, instrumentation, and technical obstacles were all critically analyzed and reported. After modifying the technique based on experience gained in the cadaver study, eight LD muscles were robotically harvested and transferred in eight patients. Access included a short axillary incision and two additional port sites along the anterior border of the muscle. Insufflation was used to maintain the optical cavity. Indications included pedicled flaps for implant-based breast reconstruction and free flaps for scalp reconstruction. All flaps were successfully transferred without converting to open technique. In the clinical series, average time for setup and port placement was 23 minutes, and average robotic time was 1 hour and 51 minutes. There were no major complications. Robotic harvest of the LD is feasible and effective and permits full muscle harvest without a visible incision.

    View details for DOI 10.1055/s-0032-1315789

    View details for Web of Science ID 000307630200005

    View details for PubMedID 22744894

  • Transoral robotic surgery: A multicenter study to assess feasibility, safety, and surgical margins LARYNGOSCOPE Weinstein, G. S., O'Malley, B. W., Magnuson, J. S., Carroll, W. R., Olsen, K. D., Daio, L., Moore, E. J., Holsinger, F. C. 2012; 122 (8): 1701-1707

    Abstract

    Our objective was to determine the safety, feasibility, and the adequacy of surgical margins for transoral robotic surgery (TORS), by reviewing the early results from independent institutional review board-approved clinical trials in three separate institutions.Pooled Data from Independent Prospective Clinical Trials.One hundred ninety-two patients were initially screened, but inadequate exposure did not permit TORS in 13 (6.7%). For two additional patients, TORS was begun but intraoperatively converted to an open procedure. Thus, the intent-to-treat population was 177 patients (average age, 59 years; 81% male), predominantly comprised of tumors arising in the oropharynx (139, 78%) and larynx (26, 15%). TORS was performed for 161 (91%) patients with malignant disease: 153 (95%) with squamous cell carcinoma (T1 [50, 32.7%], T2 [74, 48.4%], T3 [21, 13.7%], T4 [8, 5.2%]), six patients (3.72%) with salivary gland tumors, and two patients with carcinoma in situ. The average follow-up was 345 days.There was no intraoperative mortality or death in the immediate postoperative period. Average estimated blood loss was 83 mL; no patient required transfusion. The rate of positive margins was 4.3%. Twenty-nine patients (16%) experienced 34 serious adverse events that required hospitalization or intervention (grade 3) or were considered life threatening (grade 4, 2.3%). Tracheostomy was performed in 12.4% of all patients (22/177), but only 2.3% had a tracheostomy at last follow-up. For all patients undergoing TORS without previous therapy, the percutaneous endoscopic gastrostomy dependency rate was 5.0%. The average hospital stay was 4.2 days.Based on this multicenter study, TORS appears to be safe, feasible, and as such play an important role in the multidisciplinary management of head and neck cancer.

    View details for DOI 10.1002/lary.23294

    View details for Web of Science ID 000306894500012

    View details for PubMedID 22752997

  • Osteosarcoma of the jaw in children and young adults HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK Huh, W. W., Holsinger, F. C., Levy, A., Palla, F. S., Anderson, P. M. 2012; 34 (7): 981-984

    Abstract

    Pediatric jaw osteosarcoma is uncommon, and data are scarce regarding clinical presentation, prognostic factors, and outcome.A single-institution medical record review from 1983 to 2008 for 12 patients age ? 21 years was undertaken for this study.Median diagnosis age was 16.3 years (range, 6.3-21.9). Nine patients had mandible tumors. Osteoblastic subtype was most common (4 patients). Most tumors were large (ie, T2; n = 8) and high-grade (n = 8). Treatment characteristics were varied. Median follow-up was 27.1 months (range, 8-252 months). Five patients had tumor necrosis <80% after chemotherapy. No deaths were observed.Jaw osteosarcoma outcome is better compared to extremity osteosarcoma, but further study is required regarding clinical prognostic factors.

    View details for DOI 10.1002/hed.21850

    View details for Web of Science ID 000305513100011

    View details for PubMedID 21853501

  • Robotic Latissimus Dorsi Muscle Harvest: A Case Series PLASTIC AND RECONSTRUCTIVE SURGERY Selber, J. C., Baumann, D. P., Holsinger, F. C. 2012; 129 (6): 1305-1312

    Abstract

    The latissimus dorsi muscle is a workhorse of reconstructive surgery. Traditional harvest technique requires a long, posterior donor-site incision. Endoscopic harvest is limited by technical challenges. Robotic technology permits a simpler, minimally invasive harvest technique.Seven consecutive robotic latissimus dorsi muscle harvests were performed by a single surgeon. Two were used as free flaps for scalp reconstruction and the remaining five as pedicled flaps for breast reconstruction; three were for immediate, implant-based reconstruction with nipple-areola complex-sparing mastectomies, and two were for radiated breasts when the expander was exchanged for an implant. Harvest technique employed a short, axillary incision for pedicle dissection and two to three additional ports for robotic instrumentation.All seven muscle flaps were harvested without converting to an open technique. Both free flaps were successfully transferred. All pedicled flaps resulted in successful breast reconstructions. Flap harvest complications included a single, temporary radial nerve palsy in the contralateral extremity, likely from positioning. There were no donor-site hematomas, seromas, or cutaneous thermal injuries. Robotic harvest time decreased from over 2 hours to about an hour over the study period.Robotic harvest of the latissimus dorsi is a novel and effective method of muscle harvest. It offers technical advantages over endoscopic harvest and aesthetic advantages over the open technique.Therapeutic, IV.

    View details for DOI 10.1097/PRS.0b013e31824ecc0b

    View details for Web of Science ID 000304648500043

    View details for PubMedID 22634647

  • Robotic transaxillary thyroidectomy with gasless approach in a girl with goitre INTERNATIONAL JOURNAL OF MEDICAL ROBOTICS AND COMPUTER ASSISTED SURGERY Kandil, E., Noureldine, S., Khalek, M. A., Aslam, R., Ekaidi, I., Steiner, R., Holsinger, F. C. 2012; 8 (2): 210-214

    Abstract

    Robotic-assisted transaxillary thyroidectomy is a minimally invasive approach for the removal of the thyroid through the axilla. This technique eliminates a visible scar and affords excellent optics of the cervical anatomy. We sought to describe the technique and outcome for transaxillary gasless subtotal thyroidectomy in the paediatric population.A 13?year-old female with an enlarged goitre underwent a transaxillary robot-assisted gasless subtotal thyroidectomy in an academic institution. The main outcome measures were feasibility of the robotic approach, patient and gland characteristics, operative time and complications.There was no conversion to laparoscopic or open surgery. The robotic docking time was 110?min and total operative time was 150?min. The patient tolerated the procedure well. Estimated blood loss was 10?ml. The patient was discharged within 24?h. There were no perioperative or postoperative complications. In addition there was no evidence of postoperative vocal cord palsy or paresis.This initial experience demonstrates that this technique can be a feasible, safe and effective method for subtotal thyroidectomy in the paediatric population. The use of robotic technology for endoscopic thyroid surgery could overcome the limitations of conventional endoscopic surgeries in the surgical management of thyroid disease.

    View details for DOI 10.1002/rcs.455

    View details for Web of Science ID 000304470500012

    View details for PubMedID 22454366

  • Functional Organ Preservation for Laryngeal Cancer: Past, Present and Future JAPANESE JOURNAL OF CLINICAL ONCOLOGY Nakayama, M., Laccourreye, O., Holsinger, F. C., Okamoto, M., Hayakawa, K. 2012; 42 (3): 155-160

    Abstract

    Management of laryngeal cancer has focused on improving survival while preserving function. Over the past 20 years, the trends have shifted from surgery to chemoradiotherapy and presently we are facing various challenges. It is imperative to re-examine what has happened and what can be done.Review of the literature along with our experience in the management of functional organ preservation for laryngeal cancer.There was an increasing use of chemoradiotherapy with a decreasing use of surgery. Inappropriate patient selection along with inability to properly apply salvage surgeries have been presumed to be responsible for survival deterioration in laryngeal cancer. Reports concerning late adverse events after chemoradiotherapy are also increasing. Reconfirmation of the multidisciplinary team approach is imperative. Transoral laser microsurgery can be used for early laryngeal cancer and, in some experienced institutes, for advanced-stage cancers. Supracricoid laryngectomy demonstrated satisfactory oncologic and functional outcomes, based on our experience.Treatment selection for larynx preservation should not merely be decided by guidelines but considering each patient's individual condition. Head and neck surgeons are encouraged to take reasonable risks in performing salvage larynx preservation surgery when it is the only option to save a functioning larynx.

    View details for DOI 10.1093/jjco/hyr190

    View details for Web of Science ID 000301067700001

    View details for PubMedID 22223858

  • Initial experience using robot- assisted transaxillary thyroidectomy for Graves' disease JOURNAL OF VISCERAL SURGERY Kandil, E., Noureldine, S., Khalek, M. A., Alrasheedi, S., Aslam, R., Friedlander, P., Holsinger, F. C., Bellows, C. F. 2011; 148 (6): E447-E451

    Abstract

    Graves' disease is the most common form of hyperthyroidism and surgery to remove the thyroid gland is a common treatment option for many of these patients. Interestingly, due to the enlarged gland size, their high vascularity, and the difficulty to control bleeding, many authors feel that Graves' disease remains a contraindication to current endoscopic techniques. We hypothesize that performing robotic subtotal thyroidectomy in Graves' disease settings could overcome the limitations of conventional endoscopic surgeries in the surgical management of this challenging thyroid disease.Prospective study in an academic hospital.Sixty-seven patients had robotic transaxillary thyroidectomy within a year. Of these, five cases (7%) were done for Graves' disease. There were three females and two males (mean age, 36 years). There were no conversions to laparoscopic or open surgery. The mean (SD) thyroid volume was 16.6 (3.2) ml. The mean (SD) operative time was 159 (17.8)min and docking time was 81 (20)min. Mean blood loss was 18 mL. All patients were discharged home in 24h. There were no perioperative or postoperative complications. There was no evidence of postoperative vocal cord palsy or paresis.We showed that robotic transaxillary thyroidectomy is feasible and can be safe and effective in patients with Graves' disease. To our knowledge, this is the first article describing this approach for Graves' disease. These findings, however, warrant additional investigation within future prospective clinical trials.

    View details for DOI 10.1016/j.jviscsurg.2011.10.002

    View details for Web of Science ID 000298150100008

    View details for PubMedID 22118896

  • ASPIRATION AFTER SUPRACRICOID PARTIAL LARYNGECTOMY: INCIDENCE, RISK FACTORS, MANAGEMENT, AND OUTCOMES HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK Benito, J., Holsinger, F. C., Perez-Martin, A., Garcia, D., Weinstein, G. S., Laccourreye, O. 2011; 33 (5): 679-685

    Abstract

    The aim of this study was to evaluate the incidence, risk factors, management, and outcome of postoperative aspiration in patients managed with a supracricoid partial laryngectomy (SCPL) for selected invasive squamous carcinoma of the larynx.In all, 457 patients underwent SCPL at an academic, tertiary referral care center, 1975-2000. The incidence of aspiration defined in accord with Pearson's scale was recorded. Univariate and multivariate analyses were performed for potential statistical relation with various variables. The management and outcome of aspiration are presented.Normal swallowing without aspiration was noted in 259 patients (58.9%). Grades 1, 2, and 3 aspiration occurred in 87, 48, and 53 patients (19%, 10.5%, and 11.6%), respectively. A significant relationship was noted between aspiration and increased age, performing cricohyoidopexy, not repositioning the pyriform sinuses, and resecting an arytenoid cartilage. A prediction model, based on multinomial logistic regression, found that the probability that severe aspiration cases (grade 2-3) exceeded the subclinical ones (grade 0-1) occurred only when a cricohyoidopexy with partial or total arytenoid resection was performed in patients >70 years of age (p = .0000001). Management of aspiration required a temporary gastrostomy, a permanent gastrostomy, and a completion total laryngectomy in 65, 3, and 7 of 188 patients (34.5%, 1.6%, and 3.7%, respectively) who aspirated, and 65, 3, and 7 of 457 of the entire population (14.2%, 0.6%, and 1.5%, respectively). Aspiration-related death was not encountered in the current series.Aspiration after SCPL is a common but rarely severe event, with a low incidence for permanent gastrostomy or completion laryngectomy. Aspiration can be minimized with careful patient selection and precise surgical technique.

    View details for DOI 10.1002/hed.21521

    View details for Web of Science ID 000289379200012

    View details for PubMedID 20737502

  • Robot assisted transaxillary surgery (RATS) for the removal of thyroid and parathyroid glands SURGERY Landry, C. S., Grubbs, E. G., Morris, G. S., Turner, N. S., Holsinger, F. C., Lee, J. E., Perrier, N. D. 2011; 149 (4): 549-555

    Abstract

    Robotic assisted transaxillary surgery (RATS) is a minimally invasive approach for the removal of the thyroid and/or parathyroid glands through the axilla. This anatomically directed technique, popularized by Chung, eliminates a visible scar and affords excellent high definition optics of the cervical anatomy. We report an initial series of single access RATS in the U.S.The prospective endocrine surgery database at a tertiary care center was used to capture all patients who underwent RATS between October 2009 and March 2010. All procedures were performed using a single transaxillary incision.Fourteen operations were performed on 13 patients. Indications for RATS were indeterminate thyroid nodules in 11 patients, the need for completion thyroidectomy in 1 patient, and primary hyperparathyroidism in 2 patients. For patients who underwent robotic assisted thyroid lobectomy, the median thyroid nodule size was 2.1 cm (range, 0.8-2.8 cm), and the median body mass index was 25.33 (range, 21.3-34.4). Mean and median total operative times for robotic assisted thyroid lobectomies were 142 minutes and 137 minutes respectively (range, 113-192 minutes). Operative time for the 2 patients who underwent robotic assisted parathyroidectomy was 115 and 102 minutes. Minor complications occurred in 4 patients (28.5%), with no significant perioperative morbidity or mortality.RATS is feasible. We believe that further study of the RATS technique for removing thyroid lobes and parathyroid glands is warranted. This initial series suggests that careful, continued investigation is necessary prior to routine implementation into clinical practice across the U.S.

    View details for DOI 10.1016/j.surg.2010.08.014

    View details for Web of Science ID 000289017500011

    View details for PubMedID 20947113

  • Sinonasal and nasopharyngeal applications of the hand-held CO2 laser fiber INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY Agarwal, G., Kupferman, M. E., Holsinger, F. C., Hanna, E. Y. 2011; 1 (2): 109-112

    Abstract

    Carbon dioxide (CO(2)) laser provides precision and excellent hemostasis, leading to healing with minimal discomfort and complications. In spite of the advantages, the application of CO(2) laser has been limited in the sinonasal region due to the difficulty in delivering laser energy to the deep, narrow, and confined spaces. The availability of flexible laser fibers and custom-designed hand pieces has rectified these limitations but, until this date, there are no data on their safety and efficacy profile.We conducted a retrospective chart review of patients who underwent sinonasal and nasopharyngeal surgery with a hand-held CO(2) laser at M.D. Anderson Cancer center between 2007 and 2009.Out of 12 patients, 3 patients had postradiotherapy adhesions, 2 patients had a recurrent sinonasal mucoepidermoid carcinoma and 1 patient each had a ganglioneuroblastoma of the nasopharynx involving the basisphenoid and clivus, recurrent spindle cell melanoma of the nasopharynx, juvenile nasopharyngeal angiofibroma, papilloma of the nasal cavity, pituitary adenoma, spindle cell lipoma of the nasopharynx, and intranasal Rosai-Dorfman disease. The CO(2) laser, along with conventional endoscopic techniques and instruments, was used at 6-12 W continuous mode, to excise the disease. Median blood loss was 88 mL with no laser-related complication in any patient.In sinonasal and nasopharyngeal regions, use of hand-held CO(2) laser fiber provides precision, excellent hemostasis and minimizes tissue manipulation thereby reducing risk to the underlying structures. Thus, it can be an important tool for rhinologists and skull-base surgeons, especially for revision and postradiotherapy cases.

    View details for DOI 10.1002/alr.20017

    View details for Web of Science ID 000308912300006

    View details for PubMedID 22287328

  • Initial experience with transoral robotic surgery using the da VinciA (R) surgical system HNO Simon, C., El-Baba, B., Albrecht, T., Holsinger, F. C., Plinkert, P. K. 2011; 59 (3): 261-265

    Abstract

    Transoral robotic surgery (TORS) can be considered an extension of transoral microscopic laser surgery. The microscope is replaced by an endoscope that provides the surgeon with a three-dimensional view of the surgical field. The surgeon operates from a console that controls the arms of the patient cart. These arms hold miniaturized surgical instruments that are transorally inserted into the patient, enabling tumor resection. Exposure is ensured by various mouth gags. The use of various endoscopes (0°, 30°), a work radius of 540° for instruments, and a zoom function provides significant advantages over the common transoral laser techniques. With this article we report our first experience with this technique and believe that it may provide significant advantages. However, thorough clinical testing in Germany is required before conclusions can be drawn.

    View details for DOI 10.1007/s00106-010-2254-z

    View details for Web of Science ID 000288556100007

    View details for PubMedID 21424364

  • Robotic Thyroid Surgery: An Initial Experience with North American Patients LARYNGOSCOPE Kuppersmith, R. B., Holsinger, F. C. 2011; 121 (3): 521-526

    Abstract

    To review the initial experience of gasless transaxillary robot-assisted endoscopic thyroid surgery in a series of patients and describe modifications of the technique for the North American patients, selection criteria, and other issues related to this technology.Retrospective review of the first 31 consecutive cases at a single institution.Thirty-one patients underwent robotic thyroid surgery. Twenty thyroid lobectomies and 11 total thyroidectomies were performed. Improvements in the length of time to perform components of the procedure were noted from the early group of cases to later group of cases. No major or permanent complications occurred.Robotic thyroid surgery is feasible in North American patients and can be safely performed. The procedure has potential complications and a definite learning curve exists for both surgeons and operating room staff. Training methods need to be validated to ensure safe adoption. More studies need to be performed to further evaluate the relative benefits of this technique.

    View details for DOI 10.1002/lary.21347

    View details for Web of Science ID 000287789400014

    View details for PubMedID 21344427

  • Transoral robotic-assisted thyroidectomy with central neck dissection: preclinical cadaver feasibility study and proposed surgical technique. Journal of robotic surgery Richmon, J. D., Holsinger, F. C., Kandil, E., Moore, M. W., Garcia, J. A., Tufano, R. P. 2011; 5 (4): 279-282

    Abstract

    Recently, a transoral robotic-assisted technique to access the thyroid gland has been introduced. Despite the advantages this approach may have over other minimally invasive and robotic-assisted techniques, we found that the placement of the camera through the floor of mouth led to restricted freedom of movement. We describe our modification to this technique to overcome this problem. In a study using two fresh human cadavers, the camera port of the da Vinci robot was placed in the midline oral vestibule instead of the floor of the mouth. A transoral thyroidectomy and central neck dissection was successfully performed. Our modification led to an unfettered view of the central neck and allowed for a total thyroidectomy and central neck dissection. Our modification of transoral robotic-assisted thyroidectomy provides superior access to the central compartment of the neck over other robotic-assisted thyroidectomy techniques. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11701-011-0287-2) contains supplementary material, which is available to authorized users.

    View details for PubMedID 22162981

  • CRTC1/MAML2 fusion transcript in central mucoepidermoid carcinoma of mandible-diagnostic and histogenetic implications ANNALS OF DIAGNOSTIC PATHOLOGY Bell, D., Holsinger, C. F., El-Naggar, A. K. 2010; 14 (6): 396-401

    Abstract

    Intraosseous salivary gland carcinomas are extremely rare, comprising only 2% to 3% of all mucoepidermoid carcinomas (MECs) reported. The t(11;19) translocation and its CRTC1/MAML1 fusion transcript have been identified in MEC at different sites and are believed to be associated with the development of a subset of these tumors. However, the status of the fusion transcript has not been reported in intraosseous MEC. Here, we report 3 examples of central MEC of the mandible, including a case with a history of primary retromolar MEC. Reverse transcriptase-polymerase chain reaction and DNA sequencing analyses of the microdissected components of these tumors were used for the detection and verification of the fusion transcript. We identified, for the first time, the t(11;19) fusion gene transcript in central MEC, including in the previous primary retromolar MEC. No fusion transcript was detected in the second primary noncentral MEC or in another central MEC. The results indicate that central MEC can manifest the fusion transcript. This finding may have diagnostic and histogenetic roles in the future analysis of this entity.

    View details for DOI 10.1016/j.anndiagpath.2010.05.009

    View details for Web of Science ID 000284673200002

    View details for PubMedID 21074686

  • Prereferral Head and Neck Cancer Treatment Compliance With National Comprehensive Cancer Network Treatment Guidelines ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY Lewis, C. M., Hessel, A. C., Roberts, D. B., Guo, Y. Z., Holsinger, F. C., Ginsberg, L. E., El-Naggar, A. K., Weber, R. S. 2010; 136 (12): 1205-1211

    Abstract

    to evaluate the prereferral treatment of patients referred to our tertiary care center with recurrent or persistent head and neck cancer for compliance with National Comprehensive Cancer Network (NCCN) guidelines.a prospective recruitment and retrospective chart review.the study included new patients identified at multidisciplinary treatment planning conference from October 1, 2008, to February 1, 2009, who had received prior treatment at an outside institution and presented to our department with recurrent or persistent disease.all facets of prior care were examined, including the time from initial symptoms to diagnosis and whether their prereferral treatment was compliant with or deviated from NCCN guidelines for head and neck cancer.a total of 566 consecutive new patients were identified, of whom 107 (18.9%) had persistent or recurrent disease. The average time from first presentation with initial symptoms to diagnosis among patients who presented with persistent disease was 23.8 weeks. Nearly half of the patients who presented with persistent or recurrent disease had either endocrine (21.5%) or cutaneous (24.2%) primary cancers, with the rest of the cases being distributed among 10 other sites. Of the patients who presented with recurrent or persistent disease, 43.0% had prereferral care that was noncompliant with NCCN guidelines. Of these patients, 58.7% had inadequate surgical management, 15.2% were treated for the wrong diagnosis, 10.9% received inadequate adjuvant therapy, 4.4% received inadequate radiotherapy, and 10.9% refused indicated recommended treatment.significant deviation from NCCN guidelines for head and neck cancer treatment was observed in the cohort of study patients. The failure to administer adjuvant therapy when indicated by NCCN guidelines is particularly concerning. Economic and noneconomic costs, including lost wages, cost of "do-over" therapy, and potentially diminished survival, are substantial. Measures to ensure that patients receive therapy according to guidelines should be a national priority.

    View details for Web of Science ID 000285323000006

    View details for PubMedID 21173369

  • CANDIDATE DOSIMETRIC PREDICTORS OF LONG-TERM SWALLOWING DYSFUNCTION AFTER OROPHARYNGEAL INTENSITY-MODULATED RADIOTHERAPY INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Schwartz, D. L., Hutcheson, K., Barringer, D., Tucker, S. L., Kies, M., Holsinger, F. C., Ang, K. K., Morrison, W. H., Rosenthal, D. I., Garden, A. S., Dong, L., Lewin, J. S. 2010; 78 (5): 1356-1365

    Abstract

    To investigate long-term swallowing function in oropharyngeal cancer patients treated with intensity-modulated radiotherapy (IMRT), and to identify novel dose-limiting criteria predictive for dysphagia.Thirty-one patients with Stage IV oropharyngeal squamous carcinoma enrolled on a Phase II trial were prospectively evaluated by modified barium swallow studies at baseline, and 6, 12, and 24 months post-IMRT treatment. Candidate dysphagia-associated organs at risk were retrospectively contoured into original treatment plans. Twenty-one (68%) cases were base of tongue and 10 (32%) were tonsil. Stage distribution was T1 (12 patients), T2 (10), T3 (4), T4 (2), and TX (3), and N2 (24), N3 (5), and NX (2). Median age was 52.8 years (range, 42-78 years). Thirteen patients (42%) received concurrent chemotherapy during IMRT. Thirteen (42%) were former smokers. Mean dose to glottic larynx for the cohort was limited to 18 Gy (range, 6-39 Gy) by matching IMRT to conventional low-neck fields.Dose-volume constraints (V30 < 65% and V35 < 35% for anterior oral cavity and V55 < 80% and V65 < 30% for high superior pharyngeal constrictors) predictive for objective swallowing dysfunction were identified by univariate and multivariate analyses. Aspiration and feeding tube dependence were observed in only 1 patient at 24 months.In the context of glottic laryngeal shielding, we describe candidate oral cavity and superior pharyngeal constrictor organs at risk and dose-volume constraints associated with preserved long-term swallowing function; these constraints are currently undergoing prospective validation. Strict protection of the glottic larynx via beam-split IMRT techniques promises to make chronic aspiration an uncommon outcome.

    View details for DOI 10.1016/j.ijrobp.2009.10.002

    View details for Web of Science ID 000284987800010

    View details for PubMedID 20646872

  • Differential diagnosis of pediatric tumors of the nasal cavity and paranasal sinuses: A 45-year multi-institutional review ENT-EAR NOSE & THROAT JOURNAL Holsinger, F. C., Hafemeister, A. C., Hicks, M. J., Sulek, M., Huh, W. W., Friedman, E. M. 2010; 89 (11): 534-?

    Abstract

    We conducted a retrospective case-series review to identify the various diagnoses of neoplasms of the nasal cavity and paranasal sinuses in a pediatric population. Our study group was made up of 54 children-23 boys and 31 girls, aged 8 months to 16 years (mean: 9 yr). All patients had been diagnosed with a tumor of the nasal cavity or paranasal sinuses between Jan. 1, 1955, and Dec. 31, 1999, at one of four university-based, tertiary care referral centers. We compiled data on tumoral characteristics (location, size, and histopathology), morbidity and mortality, and rates of recurrence. Lesions included adnexal neoplasm, ameloblastic fibro-odontoma, basal cell carcinoma, benign fibrous histiocytoma, blue nevus, chondrosarcoma, compound nevus, epithelioma adenoides cysticum, esthesioneuroblastoma, Ewing sarcoma, fibrosarcoma, giant cell granuloma, granulocytic sarcoma, hemangioma, hemangiopericytoma, Langerhans cell histiocytosis, lymphangioma, lymphoma, melanoma, neuroblastoma, neurofibroma, ossifying osteofibroma, osteochondroma, osteosarcoma, port wine stain, rhabdomyosarcoma, Spitz nevus, and xanthogranuloma. To the best of our knowledge, this is the largest such study of its kind to date. We believe that the large size of this study and the data on disease incidence will allow clinicians to be better informed of the differential diagnosis of neoplasms of the nasal cavity and paranasal sinuses in the pediatric population.

    View details for Web of Science ID 000284921400007

    View details for PubMedID 21086277

  • A Shifting Paradigm for Patients with Head and Neck Cancer: Transoral Robotic Surgery (TORS) ONCOLOGY-NEW YORK Bhayani, M. K., Holsinger, F. C., Lai, S. Y. 2010; 24 (11): 1010-1015

    Abstract

    The evolution of surgical oncologic technology has moved toward reducing patient morbidity without compromising oncologic resection. In head and neck surgery, organ-preserving techniques have paved the way for the development of transoral techniques that remove tumors of the upper aerodigestive tract without external incisions and potentially spare the patient adjuvant treatment. The introduction of transoral robotic surgery (TORS) improves upon current transoral techniques to the oropharynx and supraglottis. This review will report on the evolution of robotic-assisted surgery: We will cover its applications in head and neck surgery by examining early oncologic and functional outcomes, training of surgeons, costs, and future directions.

    View details for Web of Science ID 000293341200006

    View details for PubMedID 21155450

  • SIMPLE CAROTID-SPARING INTENSITY-MODULATED RADIOTHERAPY TECHNIQUE AND PRELIMINARY EXPERIENCE FOR T1-2 GLOTTIC CANCER INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Rosenthal, D. I., Fuller, C. D., Barker, J. L., Mason, B., Garcia, J. A., Lewin, J. S., Holsinger, F. C., Stasney, C. R., Frank, S. J., Schwartz, D. L., Morrison, W. H., Garden, A. S., Ang, K. K. 2010; 77 (2): 455-461

    Abstract

    To investigate the dosimetry and feasibility of carotid-sparing intensity-modulated radiotherapy (IMRT) for early glottic cancer and to report preliminary clinical experience.Digital Imaging and Communications in Medicine radiotherapy (DICOM-RT) datasets from 6 T1-2 conventionally treated glottic cancer patients were used to create both conventional IMRT plans. We developed a simplified IMRT planning algorithm with three fields and limited segments. Conventional and IMRT plans were compared using generalized equivalent uniform dose and dose-volume parameters for in-field carotid arteries, target volumes, and organs at risk. We have treated 11 patients with this simplified IMRT technique.Intensity-modulated radiotherapy consistently reduced radiation dose to the carotid arteries (p < 0.05) while maintaining the clinical target volume coverage. With conventional planning, median carotid V35, V50, and V63 were 100%, 100%, and 69.0%, respectively. With IMRT planning these decreased to 2%, 0%, and 0%, respectively (p < 0.01). Radiation planning and treatment times were similar for conventional radiotherapy and IMRT. Treatment results have been excellent thus far.Intensity-modulated radiotherapy significantly reduced unnecessary radiation dose to the carotid arteries compared with conventional lateral fields while maintaining clinical target volume coverage. Further experience and longer follow-up will be required to demonstrate outcomes for cancer control and carotid artery effects.

    View details for DOI 10.1016/j.ijrobp.2009.04.061

    View details for Web of Science ID 000278167500019

    View details for PubMedID 19679406

  • Serum Signature of Hypoxia-Regulated Factors Is Associated with Progression after Induction Therapy in Head and Neck Squamous Cell Cancer MOLECULAR CANCER THERAPEUTICS Byers, L. A., Holsinger, F. C., Kies, M. S., William, W. N., El-Naggar, A. K., Lee, J. J., Hu, J., Lopez, A., Tran, H. T., Yan, S., Du, Z., Ang, K. K., Glisson, B. S., Raso, M. G., Wistuba, I. I., Myers, J. N., Hong, W., Papadimitrakopoulou, V., Lippman, S. M., Heymach, J. V. 2010; 9 (6): 1755-1763

    Abstract

    Tumor hypoxia regulates many cytokines and angiogenic factors (CAF) and is associated with worse prognosis in head and neck squamous cell cancer (HNSCC). Serum CAF profiling may provide information regarding the biology of the host and tumor, prognosis, and response to therapy. We investigated 38 CAFs in HNSCC patients receiving induction therapy on a phase II trial of carboplatin, paclitaxel, and cetuximab. CAFs were measured by multiplex bead assay and enzyme-linked immunosorbent assay in 32 patients. Baseline and postinduction CAF levels were correlated with disease progression (PD) and human papilloma virus (HPV) status by Wilcoxon rank sum test. Baseline levels of eight hypoxia-regulated CAFs (the "high-risk signature" including vascular endothelial growth factor, interleukins 4 and 8, osteopontin, growth-related oncogene-alpha, eotaxin, granulocyte-colony stimulating factor, and stromal cell-derived factor-1alpha) were associated with subsequent PD. Elevation in >or=6 of 8 factors was strongly associated with shorter time to progression (P = 0.001) and was 73% specific and 100% sensitive for PD. Increasing growth-related oncogene-alpha from baseline to week 6 was also associated with PD. Progression-free and overall survival were shorter in patients with HPV-negative tumors (P = 0.012 and 0.046, respectively), but no individual CAF was associated with HPV status. However, among 14 HPV-negative patients, the high-risk CAF signature was seen in all 6 patients with PD, but only 2 of 14 without PD. In conclusion, serum CAF profiling, particularly in HPV-negative patients, may be useful for identifying those at highest risk for recurrence.

    View details for DOI 10.1158/1535-7163.MCT-09-1047

    View details for Web of Science ID 000278569200027

    View details for PubMedID 20530716

  • CURRENT CONCEPTS AND NEW HORIZONS IN CONSERVATION LARYNGEAL SURGERY: AN IMPORTANT PART OF MULTIDISCIPLINARY CARE HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK Holsinger, F. C., Nussenbaum, B., Nakayama, M., Saraiya, S., Sewnaik, A., Ark, N., Ferris, R. L., Tufano, R. P., McWhorter, A. J. 2010; 32 (5): 656-665

    Abstract

    New surgical techniques in conservation laryngeal surgery (CLS) have emerged over the past 20 years and now offer a viable "organ-preservation" approach for patients with laryngeal cancer. We review traditional and new CLS procedures and summarize the functional and oncologic outcomes of CLS in both primary and salvage settings.We searched the literature by accessing Medline for articles from 1991 to 2007 on primary or salvage surgery (open and transoral) for laryngeal neoplasms.Our review of the literature suggests that proper selection of patients for CLS can yield long-term local control rates equal to or better than those obtained using radiation-based approaches. We believe that CLS should be directly compared with radiation or chemoradiation to further refine the indications for each kind of treatment in cases of primary and recurrent/refractory laryngeal cancer.

    View details for DOI 10.1002/hed.21208

    View details for Web of Science ID 000277347100015

    View details for PubMedID 19672871

  • The Emergence of Endoscopic Head and Neck Surgery CURRENT ONCOLOGY REPORTS Holsinger, F. C., Sweeney, A. D., Jantharapattana, K., Salem, A., Weber, R. S., Chung, W. Y., Lewis, C. M., Grant, D. G. 2010; 12 (3): 216-222

    Abstract

    Endoscopic and minimally invasive techniques represent a natural evolution for the discipline of head and neck surgery. Endoscopic head and neck surgery (eHNS) encompasses transoral laser microsurgery, transoral robotic surgery, as well as video-assisted and robotic surgery of the neck and thyroid. In the next 5 years, with robotic surgery and laser technology as a common platform, we foresee the development and widespread use of eHNS procedures, via transoral and transaxillary approaches.

    View details for DOI 10.1007/s11912-010-0097-0

    View details for Web of Science ID 000287499800011

    View details for PubMedID 20425082

  • TrkB induces EMT and has a key role in invasion of head and neck squamous cell carcinoma ONCOGENE Kupferman, M. E., Jiffar, T., El-Naggar, A., Yilmaz, T., Zhou, G., Xie, T., Feng, L., Wang, J., Holsinger, F. C., Yu, D., Myers, J. N. 2010; 29 (14): 2047-2059

    Abstract

    Head and neck squamous cell carcinoma (HNSCC) remains a significant public health problem, accounting for over 5% of all cancer-related deaths, and these deaths primarily result from metastatic disease. The molecular processes involved in HNSCC pathogenesis and progression are poorly understood, and here we present experimental evidence for a direct role of the cell surface receptor tyrosine kinase, TrkB, in HNSCC tumor progression. Using immunohistochemical analysis and transcriptional profiling of archival HNSCC tumor specimens, we found that TrkB and its secreted ligand, brain-derived neurotrophic factor (BDNF), are expresses in greater than 50% of human HNSCC tumors, but not in normal upper aerodigestive tract (UADT) epithelia. Studies with HNSCC cell lines reveal that in vitro stimulation with BDNF, the ligand for TrkB, upregulates the migration and invasion of HNSCC cells, and both transient and stable suppressions of TrkB result in significant abrogation of constitutive and ligand-mediated migration and invasion. Furthermore, enforced overexpression of TrkB results in altered expression of molecular mediators of epithelial-to-mesenchymal transition (EMT), including downregulation of E-cadherin and upregulation of Twist. Using an in vivo mouse model of HNSCC, we were able to show that downregulation of TrkB suppresses tumor growth. These results directly implicate TrkB in EMT and the invasive behavior of HNSCC, and correlate with the in vivo overexpression of TrkB in human HNSCC. Taken together, these data suggest that the TrkB receptor may be a critical component in the multi-step tumor progression of HNSCC, and may be an attractive target for much needed new therapies for this disease.

    View details for DOI 10.1038/onc.2009.486

    View details for Web of Science ID 000276402800004

    View details for PubMedID 20101235

  • Robotic Thyroidectomy: Operative Technique Using a Transaxillary Endoscopic Approach Without CO2 Insufflation OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA Holsinger, F. C., Terris, D. J., Kuppersmith, R. B. 2010; 43 (2): 381-?

    Abstract

    In the last 20 years, there has been a significant increase in the diagnosis of benign and malignant thyroid tumors. With improved ultrasound technology and better access to sonographic imaging, many tumors are identified at earlier stages. Consequently, there has been an evolution in surgical technique, moving toward minimally invasive approaches. This article describes the technique of robotic thyroidectomy via transaxillary endoscopic approach without CO(2) insufflation.

    View details for DOI 10.1016/j.otc.2010.01.007

    View details for Web of Science ID 000279254100013

    View details for PubMedID 20510721

  • Transoral Robotic Free Flap Reconstruction of Oropharyngeal Defects: A Preclinical Investigation PLASTIC AND RECONSTRUCTIVE SURGERY Selber, J. C., Robb, G., Serletti, J. M., Weinstein, G., Weber, R., Holsinger, F. C. 2010; 125 (3): 896-900

    View details for DOI 10.1097/PRS.0b013e3181cb6568

    View details for Web of Science ID 000275714700017

    View details for PubMedID 20195117

  • Induction Chemotherapy and Cetuximab for Locally Advanced Squamous Cell Carcinoma of the Head and Neck: Results From a Phase II Prospective Trial JOURNAL OF CLINICAL ONCOLOGY Kies, M. S., Holsinger, F. C., Lee, J. J., William, W. N., Glisson, B. S., Lin, H. Y., Lewin, J. S., Ginsberg, L. E., Gillaspy, K. A., Massarelli, E., Byers, L., Lippman, S. M., Hong, W. K., El-Naggar, A. K., Garden, A. S., Papadimitrakopoulou, V. 2010; 28 (1): 8-14

    Abstract

    PURPOSE To determine the potential efficacy of combining cetuximab with chemotherapy in patients with advanced nodal disease, we conducted a phase II trial with induction chemotherapy (ICT) consisting of six weekly cycles of paclitaxel 135 mg/m(2) and carboplatin (area under the curve = 2) with cetuximab 400 mg/m(2) in week 1 and then 250 mg/m(2) (PCC). PATIENTS AND METHODS Forty-seven previously untreated patients (41 with oropharynx primaries; 33 men, 14 women; median age, 53 years; performance status of 0 or 1) with squamous cell carcinoma of the head and neck (SCCHN; T1-4, N2b/c/3) were treated and evaluated for clinical and radiographic response. After ICT, patients underwent risk-based local therapy, which consisted of either radiation, concomitant chemoradiotherapy, or surgery, based on tumor stage and site at diagnosis. Results After induction PCC, nine patients (19%) achieved a complete response, and 36 patients (77%) achieved a partial response. The most common grade 3 or 4 toxicity was skin rash (45%), followed by neutropenia (21%) without fever. At a median follow-up time of 33 months, locoregional or systemic disease progression was observed in six patients. The 3-year progression-free survival (PFS) and overall survival (OS) rates were 87% (95% CI, 78% to 97%) and 91% (95% CI, 84% to 99%), respectively. Human papillomavirus (HPV) 16, found in 12 (46%) of 26 biopsies, was associated with improved PFS (P = .012) and OS (P = .046). CONCLUSION ICT with weekly PCC followed by risk-based local therapy seems to be feasible, effective, and well tolerated. PFS is promising, and this sequential treatment strategy should be further investigated. Patients with HPV-positive tumors have an excellent prognosis.

    View details for DOI 10.1200/JCO.2009.23.0425

    View details for Web of Science ID 000273103900004

    View details for PubMedID 19917840

  • FEASIBILITY AND SURGICAL APPROACH OF TRANSAXILLARY ROBOTIC THYROIDECTOMY WITHOUT CO2 INSUFFLATION HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK Lewis, C. M., Chung, W. Y., Holsinger, F. C. 2010; 32 (1): 121-126

    Abstract

    Our objective was to evaluate the anatomic basis for robotic-assisted transaxillary thyroidectomy and to determine its feasibility in a prospective clinical trial.Using the da Vinci Surgical Robotic System, we performed 5 cadaveric dissections, via transaxillary approach without gas insufflation. Once the safety and feasibility of this approach had been demonstrated in cadavers, it was utilized to perform a thyroid lobectomy in a patient. The da Vinci system provided excellent visualization of the recurrent and superior laryngeal nerves, parathyroid glands, and paratracheal lymphatics. After the 5 cadaver dissections, the procedure time diminished from >90 minutes to <30 minutes.Robotic-assisted transaxillary thyroidectomy is feasible with proper instrumentation and an understanding of the surgical anatomy. Based on this preclinical laboratory study and our experience in 1 patient, further evaluation of this approach in the setting of a prospective clinical trial is warranted to determine standardized criteria identifying patients who would benefit from this approach.

    View details for DOI 10.1002/hed.21318

    View details for Web of Science ID 000273384200016

    View details for PubMedID 19998442

  • Secondary Tracheoesophageal Puncture With In-Office Transnasal Esophagoscopy ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LeBert, B., McWhorter, A. J., Kunduk, M., Walvekar, R. R., Lewin, J. S., Hutcheson, K. A., Barringer, D. A., Hessel, A. C., Holsinger, F. C. 2009; 135 (12): 1190-1194

    Abstract

    To evaluate the outcomes of voice restoration using office-based transnasal esophagoscopy (TNE) to guide placement of the secondary tracheoesophageal puncture (TEP).Retrospective chart review.Two tertiary care medical centers.The study included 39 patients who underwent the TNE-TEP procedure from January 2004 to December 2008.Clinical, demographic, and TE speech-related data were recorded to examine the ease, efficiency, complications, and speech-related outcomes.Among 39 patients identified, the average age was 65 years (age range, 47-83 years), with 32 male (82%) and 7 female (16%) patients. Twenty-five patients (64%) underwent total laryngectomy; 8 (21%) underwent total laryngectomy with partial pharyngectomy; and 14 (36%) underwent microvascular flap reconstruction. The overall success rate of secondary TNE-assisted TEP placement was 97% (n = 38), with 1 unsuccessful attempt. There was no statistically significant correlation found between patients having undergone radiation therapy (either before or after oncologic resection) or a cricopharyngeal myotomy and successful TEP placement, type of reconstruction used to close the pharyngeal defect when compared with the difficulty in the placement of the TEP, development of complications associated with TEP placement, use of the TEP prosthesis, or speech intelligibility at the last follow-up visit. Thirty-one patients (79%) were still using their TEP prosthesis for speech at the last follow-up visit. Of the patients reviewed, 28 (72%) had understandable TE speech.In-office TNE-assisted TEP placement can safely be performed, with excellent speech outcomes. Reconstruction with musculocutaneous or microvascular free-tissue transfer did not limit our ability to place secondary TEPs with TNE.

    View details for Web of Science ID 000272626200001

    View details for PubMedID 20026814

  • Advanced approaches for thyroid surgery OTOLARYNGOLOGY-HEAD AND NECK SURGERY Kuppersmith, R. B., Salem, A., Holsinger, F. C. 2009; 141 (3): 340-342

    Abstract

    Over the past several years, new surgical approaches to the thyroid have been described, and efforts to further refine thyroid surgery continue. These new approaches can be classified by the anatomic location that access is obtained and whether CO(2) insufflation is necessary for the procedure to be performed. While these new approaches provide the potential for exciting innovation, more work should be done to refine some of these techniques and study the implications of adopting them from the perspective of patient outcomes and cost.

    View details for DOI 10.1016/j.otohns.2009.05.029

    View details for Web of Science ID 000269604300007

    View details for PubMedID 19716010

  • Transantral robotic access to the pituitary gland OTOLARYNGOLOGY-HEAD AND NECK SURGERY Kupferman, M., DeMonte, F., Holsinger, F. C., Hanna, E. 2009; 141 (3): 413-415

    View details for DOI 10.1016/j.otohns.2009.05.028

    View details for Web of Science ID 000269604300020

    View details for PubMedID 19716023

  • Platin-Based Exclusive Chemotherapy for Selected Patients With Squamous Cell Carcinoma of the Larynx and Pharynx CANCER Holsinger, F. C., Lin, H. Y., Bassot, V., Laccourreye, O. 2009; 115 (17): 3909-3918

    Abstract

    The current study was conducted to determine the long-term outcomes of patients with squamous cell carcinoma of the larynx and pharynx who were treated with platin-based exclusive chemotherapy (EC) after they achieved a complete clinical response (CCR) to induction chemotherapy.One hundred forty-two who achieved a CCR after platin-based induction chemotherapy were treated exclusively with additional chemotherapy, and 98.6% were followed for a minimum of 3 years or until death. Thirty-five patients had >10 years of follow-up.The survival rates at 1 year and 5 years were 95.8% and 61.2%, respectively. The main causes of death were metachronous second primary tumors (n = 27) and intercurrent disease (n = 21). Death related to EC was not encountered, and only 2 patients (1.4%) had grade 4 toxicity. In multivariate analysis, primary tumor arising outside the glottic larynx (P = .0001) and a Charlson comorbidity index >1 (P = .0001) were associated with a statistically significant reduction in survival. The 1-year and 5-year Kaplan-Meier local control estimates were 76.1% and 50.7%, respectively. Salvage treatment resulted in an observed final local control rate of 93% that varied from 97.2% in patients who had glottic cancer to 88.7% in patients who had tumor originating from other sites (P = .097). Combined chemotherapy with cisplatin and 5-fluorouracil (PF) allowed for the successful modulation of local therapy in 54.9% of patients.For selected patients, EC may provide long-term, durable disease control. For patients who developed recurrent disease after EC, this approach did not diminish survival and maintained function in the majority of patients. Future work should be directed toward select markers of response to PF chemotherapy with which to identify those patients who are suited optimally for this approach.

    View details for DOI 10.1002/cncr.24477

    View details for Web of Science ID 000269230700016

    View details for PubMedID 19551883

  • Extended Lateral Pharyngotomy for Selected Squamous Cell Carcinomas of the Lateral Tongue Base ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY Laccourreye, O., Seccia, V., Menard, M., Garcia, D., Vacher, C., Holsinger, F. C. 2009; 118 (6): 428-434

    Abstract

    In a retrospective review of an inception cohort of 26 patients with an isolated, previously untreated, moderately to well-differentiated invasive squamous cell carcinoma of the lateral tongue base, consecutively managed with an extended lateral pharyngotomy approach at a single tertiary referral care center, the authors review the key surgical points, highlight the potential technical pitfalls, and document the complications and long-term functional and oncological outcomes in terms of survival and local control.The adjunctive measures included induction chemotherapy, ipsilateral neck dissection, and postoperative radiotherapy, used in 96.1%, 96.1%, and 38.5% of patients, respectively. All patients but 2 were followed for at least 5 years or until death (maximum, 158 months).The significant postoperative complications included pharyngocutaneous fistula in 3 patients (11.5%) and hemorrhage requiring reoperation, partial flap necrosis, and pneumonia from aspiration in 1 patient (3.8%) each. In univariate analysis, no significant statistical relationship was noted between the significant postoperative complications noted and the variables under analysis. Overall, successful oral alimentation was achieved in 100% of patients by the first postoperative month without gastrostomy, tracheotomy, or completion total laryngectomy. There were no intraoperative or perioperative deaths. The main causes of death were metachronous second primary tumor, intercurrent disease, and distant metastasis, resulting in 84.6%, 64%, and 46.9% 1-, 3-, and 5-year Kaplan-Meier actuarial survival estimates, respectively. Two patients (7.6%) had local recurrence, resulting in 100%, 86.7%, and 86.7% 1-, 3-, and 5-year Kaplan-Meier actuarial local control estimates, respectively. As a function of T stage, the 3- and 5-year actuarial local control estimates were 100%, 87.5%, and 90.9% in patients with tumors classified as T1, T2, and T3-T4a, respectively.Such results suggest that extended lateral pharyngotomy should be integrated among the various conservative treatment options available to patients with selected carcinomas of the lateral tongue base.

    View details for Web of Science ID 000266952500005

    View details for PubMedID 19663374

  • Durable Long-Term Remission With Chemotherapy Alone for Stage II to IV Laryngeal Cancer JOURNAL OF CLINICAL ONCOLOGY Holsinger, F. C., Kies, M. S., Diaz, E. M., Gillenwater, A. M., Lewin, J. S., Ginsberg, L. E., Glisson, B. S., Garden, A. S., Ark, N., Lin, H. Y., Lee, J. J., El-Naggar, A. K., Hong, W. K., Shin, D. M., Khuri, F. R. 2009; 27 (12): 1976-1982

    Abstract

    For patients with stage II to IV laryngeal cancer, radiation therapy (RT) either alone or with concurrent chemotherapy provides the highest rate of organ preservation but can be associated with functional impairment. Thus, we studied the use of induction chemotherapy with or without conservation laryngeal surgery (CLS). Our objectives were to study the sensitivity of laryngeal cancer to platinum-based chemotherapy alone and to highlight the efficacy of CLS in this setting.Thirty-one previously untreated patients with laryngeal cancer (T2-4, N0-1, M0), who were resectable with CLS, were enrolled. Patients received three to four cycles of paclitaxel, ifosfamide, and cisplatin (TIP) chemotherapy, and response was assessed histologically. Patients with partial response (PR) proceeded to CLS. Patients achieving pathologic complete response (pCR) received an additional three cycles of TIP and no other treatment.Thirty patients were assessable for response. With TIP chemotherapy alone, 11 patients (37%) achieved pCR, 10 of whom (33%) remain alive with durable disease remission and no evidence of recurrence over a median follow-up time of 5 years. Nineteen patients (63%) treated with TIP alone achieved PR. The overall laryngeal preservation (LP) rate was 83%, and only five patients (16%) required postoperative RT. No patient required a gastrostomy tube or tracheotomy.Chemotherapy alone in selected patients with T2-4, N0-1 laryngeal cancer can provide durable disease remission at 5 years. For patients with PR, CLS provides a high rate of LP. This prospective study suggests that chemotherapy alone may cure selected patients with laryngeal cancer, warranting further prospective investigation.

    View details for DOI 10.1200/JCO.2008.17.6396

    View details for Web of Science ID 000266194700012

    View details for PubMedID 19289628

  • Clinicopathological Analyses of Fifty Supracricoid Laryngectomized Specimens: Evidence Base Supporting Minimal Margins ORL-JOURNAL FOR OTO-RHINO-LARYNGOLOGY AND ITS RELATED SPECIALTIES Nakayama, M., Holsinger, C., Okamoto, M., Seino, Y., Miyamoto, S., Takeda, M., Yokobori, S., Masaki, T., Hayashi, S. 2009; 71 (6): 305-311

    Abstract

    Supracricoid laryngectomy (SCL) is a reliable laryngeal preservation surgery. However, close surgical margins are often inevitable. Based on clinicopathological analyses of supracricoid laryngectomized specimens, we evaluated the evidence base supporting minimal margins.The distance between tumor edge and resected margin was measured macro- and microscopically at the anterior, posterior, superior and inferior edges, using 50 surgical specimens. The margins were correlated with pathological T staging and the prognoses.The anterior and posterior margins were the shortest, and the superior margin was the longest. The inferior margin was the only edge at which a positive margin was encountered. Cancer extending 10 mm below the glottal free edge significantly decreased the inferior margin.The surgical potential of SCL with cricohyoidoepiglottopexy was confirmed to be able to cope with tumor extensions showing margins of a few millimeters at the anterior, posterior and superior ends. Accurate assessment and management at the inferior margin is the key to stable local control.

    View details for DOI 10.1159/000261836

    View details for Web of Science ID 000273777100002

    View details for PubMedID 19940534

  • Maxillary osteosarcoma associated with a dental implant - Report of a case and review of the literature regarding implant-related sarcomas JOURNAL OF THE AMERICAN DENTAL ASSOCIATION McGuff, H. S., Heim-Hall, J., Holsinger, F. C., Jones, A. A., O'Dell, D. S., Hafemeister, A. C. 2008; 139 (8): 1052-1059

    Abstract

    The development of malignant neoplasms has been reported as a rare complication of the use of implanted biomaterials. The majority of these cases have been sarcomas related to orthopedic hardware. The authors present the first reported case of a sarcoma arising in association with a dental implant.A 38-year-old woman developed a low-grade chondroblastic osteosarcoma of the right maxilla 11 months after receiving a titanium dental implant. She was treated with systemic chemotherapy and then a maxillary resection. As of this publication, 47 months later, she is alive and disease-free.The use of endosseous implants has been associated with a low risk for the development of cancer. As the use of dental implants continues to expand, dentists need to be aware of this rare but devastating complication.

    View details for Web of Science ID 000258430500015

    View details for PubMedID 18682619

  • Outcomes after radiotherapy for basaloid squamous cell carcinoma of the head and neck - A case-control study CANCER Thariat, J., Ahamad, A., El-Naggar, A. K., Williams, M. D., Holsinger, F. C., Glisson, B. S., Allen, P. K., Morrison, W. H., Weber, R. S., Ang, K. K., Garden, A. S. 2008; 112 (12): 2698-2709

    Abstract

    Basaloid squamous cell carcinoma (BSCC) is an uncommon, high-grade variant of squamous cell carcinoma (SCC) of the head and neck. Its poorer prognosis compared with common SCC remains controversial. The authors investigated the outcomes of patients with BSCC who received radiotherapy and compared them with the outcomes of patients with SCC.From 1994 to 2004, 1007 patients received radiotherapy for head and neck carcinoma with lymph node involvement. The histologic types consisted of 51 BSCC, 431 poorly differentiated SCC (PSCC), and 525 well or moderately differentiated SCC (WMSCC). A case-control analysis was performed with BSCC matched against both PSCC and WMSCC to compare disease-control and survival rates.Patients with BSCC received treatment modalities similar to those received by patients with SCC: They received induction chemotherapy (12%) or concurrent chemotherapy (33%), and a median radiation dose of 70 Gray. Posttreatment viable tumor was present in 44%, 13%, and 28% of neck dissection specimens from patients with BSCC, PSCC, and WMSCC, respectively. The 5-year disease-free survival rates (63%, 77%, and 76%, respectively) and overall survival rates (85%, 70%, and 71%, respectively) demonstrated no statistically significant differences for BSCC, PSCC, or WMSCC, respectively.In this study, a poorer prognosis could not be demonstrated for irradiated patients with BSCC compared with either PSCC or WMSCC. All patients in this study had positive lymph node status, and the majority of patients (84%) had oropharyngeal cancer. The BSCC cohort did have a relatively high rate of viable tumor in their posttreatment neck dissections, and they had a relatively high rate of distant disease. On the basis of the high rate of lung metastases and the possibility of efficient salvage, the authors recommend obtaining a chest computed tomography scan during initial staging and follow-up.

    View details for DOI 10.1002/cncr.23486

    View details for Web of Science ID 000256580200011

    View details for PubMedID 18429002

  • Horizontal supraglottic partial laryngectomy for selected squamous carcinoma of the vallecula HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK Laccourreye, L., Garcia, D., Menard, M., Brasnu, D., Laccourreye, O., Holsinger, F. C. 2008; 30 (6): 756-764

    Abstract

    Our aim was to determine the incidence of local control in patients with selected squamous carcinoma of the vallecula treated with horizontal supraglottic laryngectomy; to analyze the consequences of local recurrence in terms of nodal recurrence, distant metastasis, survival, causes of death, overall local control, and laryngeal preservation; and to identify any clinical factors predictive of these outcomes.This was a retrospective nonrandomized case series in a university teaching hospital. An inception cohort of 95 previously untreated patients were followed until death or for a minimum of 5 years. According to the 2002 Union Internationale Contre le Cancer (UICC) staging classification system, the tumor was classified as T1, T2, and T3 in 13, 60, and 22 patients, respectively, while disease in 67 patients was considered to be in stages III to IV. All patients underwent a horizontal partial supraglottic partial laryngectomy. Ninety-four patients had an associated neck dissection. An induction chemotherapy regimen was used in 91 patients; postoperative radiation therapy was given for 49 patients. The main outcome measures were local recurrence, nodal recurrence, distant metastasis, and survival.The 1-, 3-, and the 5-year actuarial survival estimates were 86.3%, 64.2%, and 47.4%, respectively. Overall, the main causes of death were as follows: metachronous second primary tumor (47.2% of patients), intercurrent disease (16.7%), distant metastasis (15.3%), local recurrence (6.3%), and nodal recurrence, (4.2%). The 1-, 3-, and 5-year actuarial local recurrence rates were 4.5%, 11%, and 11%, respectively. Nine patients developed a local recurrence; 3 were successfully salvaged. Using multivariate analysis, no single variable was found to increase the risk for local recurrence. The overall laryngeal preservation rate and local control rate were 89.5% (85/95) and 93.4% (89/95), respectively. Local recurrence was associated with a significant increase in nodal recurrence (p <.04) and distant metastasis (p = .03).Based on this experience, horizontal partial supraglottic laryngectomy appears to be a valid approach for functional organ-preservation in patients with selected T1-T3 SCC of the vallecula.

    View details for DOI 10.1002/hed.20780

    View details for Web of Science ID 000256537900010

    View details for PubMedID 18286490

  • Functional analysis of swallowing outcomes after supracricoid partial laryngectomy HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK Lewin, J. S., Hutcheson, K. A., Barringer, D. A., May, A. H., Roberts, D. B., Holsinger, C., Diaz, E. M. 2008; 30 (5): 559-566

    Abstract

    In this study, we analyzed swallowing recovery after supracricoid partial laryngectomy (SCPL).We retrospectively reviewed 27 patients treated with SCPL (September 1997 to March 2005). We evaluated recovery course, nutritional outcomes, and swallowing using objective analysis. Modified barium swallow (MBS) study results identified swallowing physiology and therapeutic effectiveness.Average length of hospitalization was 7.7+/-9.2 days; time to decannulation was 5.3+/-8.2 weeks. The most common complications included pneumonia and subcutaneous emphysema (26%). Twenty-two patients had MBS studies, in which initially, all patients aspirated due to neoglottic incompetency, and impaired base of tongue and laryngeal movements. Although aspiration rates did not change significantly over time, use of appropriately selected swallowing strategies effectively protected the airway (p= .0365). Ultimately, 81% of patients returned to complete oral intake with median tube removal at 9.4 weeks.SCPL produces severe dysphagia initially. Our findings suggest that objective swallowing assessment is important for return to oral nutrition after SCPL.

    View details for DOI 10.1002/hed.20738

    View details for Web of Science ID 000255578300001

    View details for PubMedID 18098304

  • Recent advances in thyroid cancer. In brief. Current problems in surgery Grubbs, E. G., Rich, T. A., Li, G., Sturgis, E. M., Younes, M. N., Myers, J. N., Edeiken-Monroe, B., Fornage, B. D., Monroe, D. P., Staerkel, G. A., Williams, M. D., Waguespack, S. G., Hu, M. I., Cote, G., Gagel, R. F., Cohen, J., Weber, R. S., Anaya, D. A., Holsinger, F. C., Perrier, N. D., Clayman, G. L., Evans, D. B. 2008; 45 (3): 149-151

    View details for DOI 10.1067/j.cpsurg.2007.12.008

    View details for PubMedID 18346476

  • Swing of the Pendulum: Optimizing Functional Outcomes in Larynx Cancer CURRENT ONCOLOGY REPORTS Holsinger, F. C. 2008; 10 (2): 170-175

    Abstract

    For years, total laryngectomy was the only treatment option for patients with intermediate to advanced laryngeal cancer. Over the past two decades, great progress has been made in the management of this disease, with multimodality approaches aimed at laryngeal preservation reshaping the treatment landscape. In the era of chemoradiation, greater focus and attention are now directed toward functional laryngeal preservation--not simply "organ preservation." The continued development and integration of new treatment approaches, including organ preservation surgery (eg, transoral minimally invasive surgery of the head and neck, supracricoid partial laryngectomy), intensity-modulated radiotherapy, and targeted molecular therapies, offer the potential to improve clinical outcomes, function, and quality of life. Incorporation of these new approaches advances the concept of personalized medicine, with treatment strategies tailored to the circumstances and future of each patient.

    View details for Web of Science ID 000207842200012

    View details for PubMedID 18377831

  • Recent advances in thyroid cancer CURRENT PROBLEMS IN SURGERY Anonymous 2008; 45 (3): 156-?

    View details for DOI 10.1067/j.cpsurg.2007.12.010

    View details for Web of Science ID 000254483800002

    View details for PubMedID 18346477

  • Videos in clinical medicine. Examination of the larynx and pharynx. New England journal of medicine Holsinger, F. C., Kies, M. S., Weinstock, Y. E., Lewin, J. S., Hajibashi, S., Nolen, D. D., Weber, R., Laccourreye, O. 2008; 358 (3)

    View details for DOI 10.1056/NEJMvcm0706392

    View details for PubMedID 18199857

  • Management of locally invasive well-differentiated thyroid cancer SURGICAL ONCOLOGY CLINICS OF NORTH AMERICA Ark, N., Zemo, S., Nolen, D., Holsinger, E. C., Weber, R. S. 2008; 17 (1): 145-?

    Abstract

    Thyroid carcinoma invasion of the aerodigestive tract and recurrent laryngeal nerve (RLN) are important factors with increase in morbidity and mortality. Primary treatment is surgery; the decision about the extent of surgery is difficult, because preserving function is as essential as removal of the tumor. This article discusses the literature relating to the assessment of disease, surgical management, and adjuvant therapy for invasive thyroid cancer of the aerodigestive tract and RLN and makes suggestions based on the authors' experience.

    View details for DOI 10.1016/j.soc.2007.10.009

    View details for Web of Science ID 000252980700009

    View details for PubMedID 18177804

  • Robotic endoscopic surgery of the skull base ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY Hanna, E. Y., Holsinger, C., DeMonte, F., Kupferman, M. 2007; 133 (12): 1209-1214

    Abstract

    To describe a novel robotic surgical approach that allows adequate endoscopic access for resection of tumors involving the anterior and central skull base and allows 2-handed, tremor-free, endoscopic dissection and precise suturing of dural defects.Transnasal endoscopic approaches are being increasingly used for surgical access and resection of tumors of the anterior and central skull base. One major disadvantage of this approach is the inability to provide watertight dural closure and reconstruction, which limits its safety and widespread adoption in surgery of intracranial skull base tumors. Other disadvantages include limited depth perception and several ergonomic constraints. Four human cadaver specimens were used for this study. The surgical approach starts with bilateral sublabial incisions and wide anterior maxillary antrostomies (Caldwell-Luc). Transantral access to the nasal cavity is gained through bilateral wide middle meatal antrostomies. A posterior nasal septectomy facilitates bilateral access by joining both nasal cavities into 1 surgical field. The da Vinci Surgical System is then "docked" by introducing the camera arm port through the nostril and the right and left surgical arm ports through the respective anterior and middle antrostomies, into the nasal cavity. A 5-mm dual-channel endoscope coupled with a dual charge-coupled device camera is inserted in the camera port and allows for 3-dimensional visualization of the surgical field at the surgeon's console. Using the robotic surgical arms, the surgeon may perform endoscopic anterior or posterior ethmoidectomy, sphenoidotomy, or resection of the middle or superior turbinates depending on the extent of needed surgical exposure. In addition, resection of the cribriform plate is performed robotically with sharp dissection of the skull base. The dural defect is then repaired with a 6-0 nylon suture.Adequate access to the anterior and central skull base, including the cribriform plate, fovea ethmoidalis, medial orbits, planum sphenoidale, sella turcica, suprasellar and parasellar regions, nasopharynx, pterygopalatine fossa, and clivus, was obtained in all cadaveric dissections. The 3-dimensional visualization obtained by the dual-channel endoscope at the surgeon's console provided excellent depth perception. The most significant advantage was the ability of the surgeon to perform 2-handed tremor-free endoscopic closure of dural defects.Transantral robotic surgery provides adequate endoscopic access to the anterior and central skull base. To our knowledge, this is the first study to report the feasibility and advantages of robotic-assisted endoscopic surgery of the skull base. This novel approach also allows for 3-dimensional, 2-handed, tremor-free endoscopic dissection and precise closure of dural defects. These advantages may expand the indications of minimally invasive endoscopic approaches to the skull base.

    View details for Web of Science ID 000251684900004

    View details for PubMedID 18086961

  • The effect of dental artifacts, contrast media, and experience on Interobserver contouring variations in head and neck anatomy AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS O'Daniel, J. C., Rosenthal, D. I., Garden, A. S., Barker, J. L., Ahamad, A., Ang, K. K., Asper, J. A., Blanco, A. I., De Crevoisier, R., Holsinger, C., Patel, C. B., Schwartz, D. L., Wang, H., Dong, L. 2007; 30 (2): 191-198

    Abstract

    To investigate interobserver variability in the delineation of head-and-neck (H&N) anatomic structures on CT images, including the effects of image artifacts and observer experience.Nine observers (7 radiation oncologists, 1 surgeon, and 1 physician assistant) with varying levels of H&N delineation experience independently contoured H&N gross tumor volumes and critical structures on radiation therapy treatment planning CT images alongside reference diagnostic CT images for 4 patients with oropharynx cancer. Image artifacts from dental fillings partially obstructed 3 images. Differences in the structure volumes, center-of-volume positions, and boundary positions (1 SD) were measured. In-house software created three-dimensional overlap distributions, including all observers. The effects of dental artifacts and observer experience on contouring precision were investigated, and the need for contrast media was assessed.In the absence of artifacts, all 9 participants achieved reasonable precision (1 SD < or =3 mm all boundaries). The structures obscured by dental image artifacts had larger variations when measured by the 3 metrics (1 SD = 8 mm cranial/caudal boundary). Experience improved the interobserver consistency of contouring for structures obscured by artifacts (1 SD = 2 mm cranial/caudal boundary).Interobserver contouring variability for anatomic H&N structures, specifically oropharyngeal gross tumor volumes and parotid glands, was acceptable in the absence of artifacts. Dental artifacts increased the contouring variability, but experienced participants achieved reasonable precision even with artifacts present. With a staging contrast CT image as a reference, delineation on a noncontrast treatment planning CT image can achieve acceptable precision.

    View details for DOI 10.1097/01.coc.0000256704.58956.45

    View details for Web of Science ID 000245637100014

    View details for PubMedID 17414470

  • Primary adrenal natural killer/T-cell nasal type lymphoma: First case report in adults AMERICAN JOURNAL OF HEMATOLOGY Thompson, M. A., Habra, M. A., Routbort, M. J., Holsinger, F. C., Perrier, N. D., Waguespack, S. G., Rodriguez, M. A. 2007; 82 (4): 299-303

    Abstract

    We report the first case of a primary adrenal natural killer (NK)/T-cell nasal type lymphoma in adults. The patient presented with an enlarging left adrenal mass and the initial concern was for adrenocortical carcinoma. Surgical resection revealed NK/T-cell lymphoma. Rapid recurrence in the contralateral adrenal gland was treated with a single cycle of chemotherapy before he died due to infectious complications and progressive disease. This case demonstrates the aggressive presentation of a novel subset of primary adrenal lymphoma that should be considered in the differential diagnosis of a rapidly enlarging adrenal mass.

    View details for DOI 10.1002/ajh.20811

    View details for Web of Science ID 000245464400010

    View details for PubMedID 17094095

  • Swing of the surgical pendulum: A return to surgery for treatment of head and neck cancer in the 21st century? INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Holsinger, F. C., Weber, R. S. 2007; 69 (2): S129-S131

    Abstract

    Treatment for head and neck cancer has evolved significantly during the past 100 years. Beginning with Bilroth's total laryngectomy on New Year's Day in 1873, "radical" surgery remained the only accepted treatment for head and neck cancer when optimal local and regional control was the goal. Bigger was still better when it came to managing the primary tumor and the neck. The "commando" procedure and radical neck dissection were the hallmarks of this first generation of treatments of head-and-neck cancer. With the advent of microvascular reconstructive techniques, larger and more comprehensive resections could be performed. Despite these large resections and their "mutilating" sequelae, overall survival did not improve. Even for intermediate-stage disease in head-and-neck cancer, the 5-year survival rate did not improve >50%. Many concluded that more than the scalpel was needed for optimal local and regional control, especially for intermediate- and advanced-stage disease. Most important, the multidisciplinary teams must identify and correlate biomarkers in the tumor and host that predict for a response to therapy and for optimal functional recovery. As the pendulum swings back, a scientific approach using tissue biomarkers for the response to treatment in the setting of multidisciplinary trials must emerge as the new paradigm. In the postgenomic era, treatment decisions should be made based on functional and oncologic parameters-not just to avoid perceived morbidity.

    View details for DOI 10.1016/j.ijrobp.2007.05.044

    View details for Web of Science ID 000249999000037

    View details for PubMedID 17848281

  • Laryngeal preservation in the era of chemoradiation: limitations of the current AJCC staging system. Head & neck Holsinger, F. C., Diaz, E. M. 2006; 28 (12): 1058-1060

    View details for PubMedID 17099907

  • Sternocleidomastoid myofascial flap for reconstruction after composite resection of invasive squamous cell carcinoma of the tonsillar region: Technique and outcome LARYNGOSCOPE Laccourreye, O., Menard, M., Behm, E., Garcia, D., Cauchois, R., Holsinger, F. C. 2006; 116 (11): 2001-2006

    Abstract

    To present the surgical technique and determine the efficacy of sternocleidomastoid myofascial (SCMF) flap reconstruction after composite resection with intent to cure.Retrospective review of 73 consecutive patients with a previously isolated and untreated moderately to well-differentiated invasive squamous cell carcinoma of the tonsillar region and a minimum of 3 years follow-up, managed at a tertiary referral care center during the years 1970 to 2002, with an ipsilateral superiorly based SCMF flap after composite resection.The surgical procedure is presented in detail. Potential technical pitfalls are highlighted. Survival, mortality, and morbidity are documented. Univariate analysis for potential correlation between the incidence for postoperative flap complications and various variables is also performed.The 1, 3, and 5 year Kaplan-Meier actuarial survival estimates were 82.2%, 64.4%, and 49.3%, respectively. Death never appeared to be related to the completion of the SCMF flap. Thirty-three (45.2%) patients had some kind of significant postoperative surgical complication, and nine (12.3%) patients had some kind of significant postoperative medical complication. The most common significant postoperative complication was partial SCMF flap necrosis and pharyngocutaneous fistula noted in 30.1% and 10.9% of patients, respectively. Complete SCMF flap necrosis was never encountered. No patient developed carotid artery rupture or died as a result of the SCMF flap, and none required additional surgery. In univariate analysis, no significant statistical relation was noted between the significant postoperative surgical complications related to the use of the SCMF flap and the variables under analysis.The superiorly based SCMF flap appears to be simple to perform and useful for reconstruction of defects after composite resection.

    View details for DOI 10.1097/01.mlg.0000236845.51421.03

    View details for Web of Science ID 000241806300013

    View details for PubMedID 17075422

  • Conservation laryngeal surgery versus total laryngectomy for radiation failure in laryngeal cancer HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK Holsinger, F. C., Funk, E., Roberts, D. B., Diaz, E. M. 2006; 28 (9): 779-784

    Abstract

    Total laryngectomy is the standard of care for surgical salvage of radiation failure in laryngeal cancer. However, the role of conservation laryngeal surgery in this setting remains unclear. The objective was to compare the efficacy of conservation versus total laryngectomy for salvage of radiation failure in patients who initially presented with T1 or T2 squamous cancer of the larynx.A 21-year retrospective analysis of patients who received surgery at a single comprehensive cancer center after definitive radiation therapy is reported. At recurrence, the patients were reevaluated and then underwent a total laryngectomy or, if possible, a conservation laryngeal procedure. The charts of 105 patients who failed radiation treatment for primary laryngeal cancer and who subsequently underwent surgical salvage were reviewed for this study. Eighty-nine were male (84.8%). The mean age was 60.3 years. The median follow-up time after surgery was 69.4 months. Most patients with recurrence after radiotherapy required total laryngectomy (69.5%; 73/105). Conservation laryngeal surgery was performed for 32 patients (31.5%). Concomitant neck dissections were performed on 45 patients (45.5%).In 14 patients, local or regional recurrence developed after salvage surgery: 9 patients after total laryngectomy (12.3%; 9/73), and 5 patients (15.6%; 5/32) after conservation laryngeal surgery. This difference was not statistically significant, nor was there a difference in disease-free interval for the two procedures (p = .634, by log-rank test). Distant metastasis developed in 13 patients. Most developed in the setting of local and/or regional recurrence, but distant metastasis occurred as the only site of failure in 6 of the patients who had undergone total laryngectomy but in 1 of the conservation surgery patients treated for a supraglottic laryngeal cancer. The overall mortality for patients who underwent total laryngectomy was also higher: 73.74% (54/73) versus 59.4% (19/32) for patients who underwent a conservation approach (p = .011 by log-rank test).Although conservation laryngeal surgery was possible in a few patients with local failure after radiotherapy, conservation laryngeal surgery is an oncologically sound alternative to total laryngectomy for these patients.

    View details for DOI 10.1002/hed.20415

    View details for Web of Science ID 000240038300002

    View details for PubMedID 16637055

  • Resection of selected invasive squamous cell carcinoma of the pyriform sinus by means of the lateral pharyngotomy approach: The partial lateral pharyngectomy HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK Holsinger, F. C., Motamed, M., Garcia, D., Brasnu, D., Menard, M., Laccourreye, O. 2006; 28 (8): 705-711

    Abstract

    Although the lateral pharyngotomy is a well-known surgical procedure, to our knowledge, no published reports have described the results achieved with a lateral pharyngectomy approach in patients with isolated and previously untreated selected invasive squamous cell carcinoma of the lateral wall of the pyriform sinus.The medical files and operative charts of 30 patients with an isolated, and previously untreated, squamous cell carcinoma of the pyriform sinus, treated for cure by lateral partial pharyngectomy and primary closure, as well as postoperative radiotherapy (n = 22), and preoperative chemotherapy (n = 8), were retrospectively studied. Sixteen tumors were classified as T1 and 14 as T2. All patients but one were followed until death.Three patients (9%) died in the immediate postoperative period (two from medical complications and one from a surgery-related complication). Overall, 29 patients died, resulting in a 77.7%, 40%, 23.3%, and 15% 1-, 3-, 5- and 10-year Kaplan-Meier actuarial survival estimate, respectively. Only one patient had a serious postoperative complication develop. All patients were decannulated. No patients required a gastrostomy and/or completion total laryngectomy for functional reasons. Local recurrence occurred in four patients (13%). The 3-and 5-year Kaplan-Meier actuarial local control estimates were 88.5% and 79.6%, respectively. The use of a platin-based induction chemotherapy (p = .05) regimen was the only variable that was significantly statistically related to local recurrence. Overall, a 93.3% laryngeal preservation rate was achieved.Partial pharyngectomy by means of the lateral pharyngotomy combined with postoperative radiation therapy is an efficient and function-sparing approach to control selected invasive squamous cell carcinomas of the lateral wall of the pyriform sinus.

    View details for DOI 10.1002/hed.20375

    View details for Web of Science ID 000239179900006

    View details for PubMedID 16786602

  • Use of the photonic band gap fiber assembly CO2 laser system in head and neck surgical oncology LARYNGOSCOPE Holsinger, F. C., Prichard, C. N., Shapira, G., Weisberg, O., Torres, D. S., Anastassiou, C., Harel, E., Fink, Y., Weber, R. S. 2006; 116 (7): 1288-1290
  • Elective neck dissection during salvage laryngectomy AMERICAN JOURNAL OF OTOLARYNGOLOGY Yao, M., Roebuck, J. C., Holsinger, F. C., Myers, J. N. 2005; 26 (6): 388-392

    Abstract

    To evaluate the rate of occult metastases detected with elective neck dissection during salvage laryngectomy for radiation failures.Retrospective review of 63 patients failing radiation therapy treated with salvage surgery between 1970 and 1999. Charts were reviewed for tumor stage, neck treatment, complications, surgical time, and survival. Median follow-up for patients with glottic and supraglottic cancers was 7.8 and 4.5 years, respectively.Thirty-one of 41 glottic cancer patients received elective neck dissections. Three (10%) of 31 had occult metastases. Recurrent staged rT3 and greater tumors showed a 20% rate of occult metastases. No survival advantage was noted between patients treated with elective neck dissection and those followed expectantly (P = .87). Cartilage invasion and perineural invasion in the larynx were associated with a higher risk of occult metastases (P < .05). Ten of 22 supraglottic cancer patients received elective neck dissections. Two (20%) of 10 had occult metastases, and a statistically significant survival advantage was not noted (P = .49).We recommend bilateral neck dissection at the time of laryngectomy for recurrent staged rT3/4 tumors and all patients with recurrent supraglottic cancers because of the higher rate of occult metastases.

    View details for DOI 10.1016/j.amjoto.2005.05.002

    View details for Web of Science ID 000233473000005

    View details for PubMedID 16275407

  • Technical refinements in the supracricoid partial laryngectomy to optimize functional outcomes JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS Holsinger, F. C., Laccourreye, O., Weinstein, G. S., Diaz, E. M., McWhorter, A. J. 2005; 201 (5): 809-820
  • Lymph node metastases from cutaneous squamous cell carcinoma of the head and neck LARYNGOSCOPE Moore, B. A., Weber, R. S., Prieto, V., El-Naggar, A., Holsinger, F. C., Zhou, X., Lee, J. J., Lippman, S., Clayman, G. L. 2005; 115 (9): 1561-1567

    Abstract

    Cutaneous squamous cell carcinoma (CSCC) has been reported to metastasize to parotid and cervical lymph nodes. Few prospective investigations of associated clinical and histopathologic findings and their effect on patient outcomes exist. We seek to identify risk factors for nodal metastases in CSCC and determine the impact of lymphatic spread on survival and recurrence.Subset analysis of a prospective, longitudinal database of patients with CSCC at a comprehensive cancer center.Eligible patients with nonmelanoma skin cancer were consecutively enrolled in a prospective database from July 1996 through June 2001; this cohort was then followed to the key endpoints of recurrence and mortality.Two hundred ten patients were enrolled, and 193 patients with CSCC of the head and neck are included in this analysis. The incidence of nodal metastases in this population was 20.7% at study entry. Median follow-up was 20 months in patients with lymph node metastases and 24 months in patients without metastases. Nodal metastases were significantly associated with recurrent lesions (P = .002) and the following histopathologic features: lymphovascular invasion (P < .0001), inflammation (P = .010), poorly differentiated histology (P = .001), invasion into the subcutaneous tissues (P = .0001), perineural invasion (P = .005), and larger size (P = .0007). Metastases to the cervical nodes were not clinically apparent in 42% of patients with parotid metastases. Combination surgery and radiation therapy resulted in regional control rates of 95%, although local recurrence and distant metastases, along with second primary tumors, were the most frequent recurrent events. Kaplan-Meier survival analysis demonstrates a decrease in overall survival (P = .005), disease-free survival (P = .015), disease-specific survival (P = 0002), and time to recurrence (P = .012) in patients with nodal metastases compared with controls.Lymph node metastases from CSCC are common in our population and are associated with diminished survival. The presence of nodal spread occurs with other adverse histopathologic findings, and we recommend surgery and postoperative radiation therapy to control regional disease in the presence of nodal metastases and perineural invasion. New approaches in early identification of nodal metastases, treatment, and prevention of local recurrences and second primary malignancies are warranted.

    View details for DOI 10.1097/01.mlg.0000173202.56739.9f

    View details for Web of Science ID 000232047100007

    View details for PubMedID 16148695

  • Thyroplasty type I with Montgomery implant among native French language speakers with unilateral laryngeal nerve paralysis LARYNGOSCOPE Laccourreye, O., El Sharkawy, L., Holsinger, F. C., Hans, S., Menard, M., Brasnu, D. 2005; 115 (8): 1411-1417

    Abstract

    To document the long-term results achieved with the Montgomery implant in 96 French speakers with a unilateral laryngeal nerve paralysis (ULNP).Retrospective series, inception cohort of 96 patients.Data regarding morbidity and functional results were obtained at regular visits to our clinic. All patients were followed for a minimum of 6 months or until death. Forty-two patients had a minimum of 12 months of follow-up. Early in the study, 36 patients were prospectively recorded under similar conditions before placement of the Montgomery implant and at 1, 3, 6, and 12 months postoperatively.None of the 96 patients died in the immediate postoperative period. The perioperative course was unremarkable in 94.8% of cases. Perioperative problems included failure to obtain a satisfactory phonatory result in three patients, difficulty to stabilize the implant posteriorly in one patient, and fracture of the inferior rim of the thyroid cartilage window in another patient. The primary immediate postoperative problem (within the first postoperative month) was laryngeal dyspnea, noted in four patients. According to the patient's subjective assessment, speech and voice was always improved in the immediate postoperative period. However, three patients had secondary degradation of speech and voice. Revision surgery under local anesthesia resulted in a 97.9% ultimate speech and voice success rate. According to the patient's subjective assessment, adequate swallowing in the immediate postoperative period was achieved in 94.2% of cases that had swallowing problems preoperatively. A significant statistical increase in the duration parameters (phonation time, phrase grouping, speech rate) together with a statistical significant decrease in both the jitter and shimmer values was noted when comparing the preoperative and the postoperative values at 1 month. Analysis of the evolution of the speech and voice parameters at 1, 3, 6, and 12 months postoperatively showed a significant decrease in the fundamental frequency and noise-to-harmonic ratio values but did not demonstrate any significant differences for the other speech and voice parameters.From the reported data, we conclude that the type I thyroplasty with Montgomery implant insertion is a safe and reproducible method to treat ULNP. Furthermore, this system achieves very good and stable phonatory results. Finally, the use of this technique and implant system appears safe in patients from various cultures with ULNP from a variety of causes and severe comorbidity. Over the past decade at our department, this procedure progressively replaced the use of the intracordal injection of autologous fat injection that was initially advocated in patients with ULNP.

    View details for DOI 10.1097/01.mlg.0000168059.12949.a6

    View details for Web of Science ID 000231033400014

    View details for PubMedID 16094114

  • Organ-preservation laryngeal surgery in the era of chemoradiation CURRENT PROBLEMS IN CANCER Moore, B. A., Holsinger, F. C., Diaz, E. M., Weber, R. S. 2005; 29 (4): 169-179
  • Supracricoid partial laryngectomy: An organ-preservation surgery for laryngeal malignancy CURRENT PROBLEMS IN CANCER Holsinger, C., Weinstein, G. S., Laccourreye, O. 2005; 29 (4): 190-200
  • Foreword. Current problems in cancer Weber, R. S., Holsinger, F. C. 2005; 29 (4): 168-?

    View details for PubMedID 16143164

  • Transoral lateral oropharyngectomy for squamous cell carcinoma of the tonsillar region - II. An analysis of the incidence, related variables, and consequences of local recurrence ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY Laccourreye, O., Hans, S., Menard, M., Garcia, D., Brasnu, D., Holsinger, C. 2005; 131 (7): 592-599

    Abstract

    To determine the incidence of local and regional failure, distant metastasis, and overall survival following transoral lateral oropharyngectomy (TLO) and to determine factors associated with local recurrence.Retrospective case series throughout 20 years; mean follow-up of 10 years.Academic center.A total of 166 previously untreated patients with squamous cell carcinoma of the tonsil.A total of 131 (81.9%) of the 166 patients received preoperative induction chemotherapy. Fifty-one patients (30.7%) underwent postoperative radiation therapy.Local and regional recurrence, distant metastasis, second primary tumors, and survival.The 1- and 5-year Kaplan-Meier local control estimates were 91.2% and 82.1%, respectively. The 1- and 5-year Kaplan-Meier local control estimates were 98.3% and 89.0% for T1, 88.9% and 81.7% for T2, and 78.9% and 62.7% for T3 lesions, respectively (P = .02). In univariate analysis, 7 variables were significantly associated with an increased risk of local failure: increasing T classification; positive margins of resection; poor clinical response to induction chemotherapy; tumor spread to the posterior pillar, posterior pharyngeal wall, and contralateral soft palate; and invasion of the junction between the tonsil and soft palate. In a logistic regression model, spread to the posterior pillar was the only variable statistically associated with local failure (P = .02). The 1-, 3-, and 5-year Kaplan-Meier survival estimates were 87.9%, 67.2%, and 57.7%, respectively. The Kaplan-Meier survival estimate was significantly reduced (P = .009) in patients with local failure.Selected tonsillar squamous cell carcinoma can be managed with TLO with local control comparable to radiotherapy. Patient selection is critical and TLO is best suited for patients with anterior T1 to T2 squamous cell carcinoma of the tonsil, without posterior anatomic spread.

    View details for Web of Science ID 000230409300010

    View details for PubMedID 16027281

  • Transoral lateral oropharyngectomy for squamous cell carcinoma of the tonsillar region - I. Technique, complications, and functional results ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY Holsinger, F. C., McWhorter, A. J., Menard, M., Garcia, D., Laccourreye, O. 2005; 131 (7): 583-591

    Abstract

    To describe the surgical technique for transoral lateral oropharyngectomy (TLO) and its safety, postoperative management, complications, and functional outcomes.A 20-year retrospective case series review. Mean follow-up was 10 years. All but 10 patients were followed up until the fifth postoperative year or death.Academic, tertiary referral center.A total of 191 patients who underwent TLO for selected invasive squamous cell carcinoma of the tonsil and/or tonsillar fossa.Ten patients had received preoperative radiation therapy. Induction chemotherapy was used in 153 patients (80.3%). An associated neck dissection was performed in 148 patients (77.5%). Postoperative radiation therapy was administered to 52 patients (28.7%).Overall survival rate, intraoperative mortality, and perioperative mortality were determined. The need for and length of nasogastric tube feeding and tracheotomy were calculated. The incidence of significant postoperative surgical and medical complications was recorded.No intraoperative mortality occurred, but 5 patients (2.6%) died in the immediate postoperative period, 3 from medical complications and 2 from unknown causes. In this series, the internal carotid artery was never injured, and no cutaneous-oropharyngeal fistulas were apparent. The incidence of significant surgical complications from the oropharynx was 6.3%. Nasopharyngeal reflux and severe rhinolalia were the most common complications, occurring in 9 patients. Increasing tobacco use was statistically correlated with an increase in postoperative pneumonia from aspiration (P = .05) but no surgical complications. Seven patients (3.7%) had a temporary tracheotomy for a mean of 5 days. One hundred twelve patients (58.6%) had a nasogastric tube inserted for a mean of 6 days. No patients had a permanent gastrostomy or tracheotomy tube. The mean duration of hospitalization was 9 days. The duration of hospitalization was statistically correlated with the need for nasogastric tube placement and its duration (P<.001) or tracheotomy (P<.001).From a functional standpoint, the TLO is a safe surgical approach for treating selected carcinoma of the tonsillar fossa. It is a reliable technique that should be considered for treatment of appropriate squamous cell carcinoma of the tonsil.

    View details for Web of Science ID 000230409300009

    View details for PubMedID 16027280

  • Mortality risk from squamous cell skin cancer JOURNAL OF CLINICAL ONCOLOGY Clayman, G. L., Lee, J. J., Holsinger, F. C., Zhou, X., Duvic, M., El-Naggar, A. K., Prieto, V. G., Altamirano, E., Tucker, S. L., Strom, S. S., Kripke, M. L., Lippman, S. M. 2005; 23 (4): 759-765

    Abstract

    To identify nonmelanoma skin cancer patients with squamous cell carcinoma (SCC) who are at greatest risk of disease-specific mortality.Prospectively enrolled patients with a minimum of one pathologically confirmed skin SCC lesion, definitive treatment of the SCC lesion(s) resulting in no evidence of disease, and at least 2 months of follow-up after definitive treatment were eligible for the present longitudinal analysis. They received comprehensive clinical, pathologic evaluations and follow-up for patterns of failure and mortality.We enrolled 210 patients (187 men and 23 women) with a total of 277 skin SCC lesions and a median enrollment age of 68 years (range, 34 to 95 years). Median follow-up of surviving patients was 22 months. Three-year overall and disease-specific survival (DSS) rates were 70% and 85%, respectively. In univariate analyses, the clinical-pathologic factors associated with adverse DSS were local recurrence at presentation (P = .05), invasion beyond subcutaneous tissues (P = .009), perineural invasion (P = .002), lesion size (P = .0003), and depth of invasion (P = .05). Statistical models identified a homogeneous high-risk group of patients with lesions > or = 4 cm, perineural invasion, and deep invasion beyond subcutaneous structures. Three-year DSS was 100% for patients with no risk factors versus 70% for patients with at least one risk factor.Lesion size > or = 4 cm and histologic evidence of perineural invasion and deep invasion beyond subcutaneous structures were the clinical-pathologic factors most significantly associated with disease-specific mortality in skin SCC.

    View details for DOI 10.1200/JCO.2005.02.155

    View details for Web of Science ID 000226738900015

    View details for PubMedID 15681519

  • A simple method to expose the surgical field when performing a thyroplasty OTOLARYNGOLOGY-HEAD AND NECK SURGERY Laccourreye, O., Holsinger, F. C. 2005; 132 (1): 108-109

    View details for DOI 10.1016/j.otohns.2004.09.036

    View details for Web of Science ID 000226216300019

    View details for PubMedID 15632919

  • Epidermal growth factor receptor (EGFR) is overexpressed in anaplastic thyroid cancer, and the EGFR inhibitor gefitinib inhibits the growth of anaplastic thyroid cancer CLINICAL CANCER RESEARCH Schiff, B. A., McMurphy, A. B., Jasser, S. A., Younes, M. N., Doan, D., Yigitbasi, O. G., Kim, S. W., Zhou, G., Mandal, M., Bekele, B. N., Holsinger, F. C., Sherman, S. I., Yeung, S. C., El-Naggar, A. K., Myers, J. N. 2004; 10 (24): 8594-8602

    Abstract

    No effective treatment options currently are available to patients with anaplastic thyroid cancer (ATC), resulting in high mortality rates. Epidermal growth factor (EGF) has been shown to play a role in the pathogenesis of many types of cancer, and its receptor (EGFR) provides an attractive target for molecular therapy.The expression of EGFR was determined in ATC in vitro and in vivo and in human tissue arrays of ATC. We assessed the potential of the EGFR inhibitor gefitinib ("Iressa," ZD1839) to inhibit EGFR activation in vitro and in vivo, inhibit ATC cellular proliferation, induce apoptosis, and reduce the growth of ATC cells in vivo when administered alone and in combination with paclitaxel.EGFR was overexpressed in ATC cell lines in vitro and in vivo and in human ATC specimens. Activation of EGFR by EGF was blocked by the addition of gefitinib. In vitro studies showed that gefitinib greatly inhibited cellular proliferation and induced apoptosis in ATC cell lines and slowed tumor growth in a nude mouse model of thyroid carcinoma cells injected subcutaneously.ATC cells consistently overexpress EGFR, rendering this receptor a potential target for molecular therapy. Gefitinib effectively blocks activation of EGFR by EGF, inhibits ATC cellular proliferation, and induces apoptosis in vitro. Our in vivo results show that gefitinib has significant antitumor activity against ATC in a subcutaneous nude mouse tumor model and therefore is a potential candidate for human clinical trials.

    View details for Web of Science ID 000225957800061

    View details for PubMedID 15623643

  • Detection of plasminogen activators in oral cancer by laser capture microdissection combined with zymography ORAL ONCOLOGY Curino, A., Patel, V., Nielsen, B. S., Iskander, A. J., Ensley, J. F., Yoo, G. H., Holsinger, F. C., Myers, J. N., El-Nagaar, A., Kellman, R. M., Shillitoe, E. J., Molinolo, A. A., Gutkind, J. S., Bugge, T. H. 2004; 40 (10): 1026-1032

    Abstract

    Plasminogen activation is believed to be critical to the progression of oral squamous cell carcinoma by facilitating matrix degradation during invasion and metastasis, and high levels of urokinase plasminogen activator (uPA) and plasminogen activator (PA) inhibitor-1 (PAI-1) in tumors predict poor disease outcome. We describe the development of a novel method for studying PA in oral cancer that combines the sensitivity and specificity of zymography with the spatial resolution of immunohistochemistry. Laser capture microdissection (LCM) was combined with plasminogen-casein zymography to analyze uPA, tissue PA (tPA), uPA-PAI-1 complexes, and tPA-PAI-1 complexes in 11 tumors and adjacent non-malignant epithelium from squamous cell carcinomas of the tongue, floor of mouth, larynx, and vocal cord. uPA was detectable in all tumor samples analyzed, uPA-PAI-1 complexes in three samples, and tPA in nine. PA was detectable in as little as 0.5 microg protein lysate from microdissected tumors. In all specimens, uPA expression was highly increased in tumor tissue compared to adjacent non-malignant tissue. In conclusion, LCM combined with zymography may be excellently suited for analyzing the prognostic significance and causal involvement of the plasminogen activation system in oral cancer.

    View details for DOI 10.1016/j.oraloncology.2004.05.011

    View details for Web of Science ID 000225147700009

    View details for PubMedID 15509494

  • Acquisition of anoikis resistance is a critical step in the progression of oral tongue cancer ORAL ONCOLOGY Swan, E. A., Jasser, S. A., Holsinger, F. C., Doan, D., Bucana, C., Myers, J. N. 2003; 39 (7): 648-655

    Abstract

    We hypothesized that acquisition of resistance to anoikis is a critical step in oral cancer progression. To test this hypothesis, we compared a panel of cell lines derived from human oral tissues across the spectrum of tumor progression from oral keratinocytes (HOK-16B), invasive oral squamous cell carcinoma (Tu167), and finally metastatic carcinoma (TxCS-1, MDA1986) for their sensitivity to detachment from the extracellular matrix. The relationship between stage of tumor progression and anoikis resistance was demonstrated by the apoptotic fractions after 48 h in suspension culture which were 93.33, 61.6, 34.5, and 3.71%, respectively. To further demonstrate that anoikis resistance is important for tumor progression, we selected a highly anoikis resistant cell line, JMAR, by serial passage of the Tu167 cell line in suspension culture. Initially, the JMAR line, and clones derived from it, were characterized for anoikis resistance in vitro, and after 72 h in suspension culture the rates of anoikis in the Tu167 and JMAR lines were found to be 73 and 26%, respectively. The degree of anoikis resistance was found to correlate with survival of nude mice orthotopically injected with 5x10(5) Tu167 or JMAR cells. The JMAR mice had a median survival of 17 days versus over 30 days in mice implanted with the Tu167 line. Finally, we found that in vivo selection in the orthotopic model for a regionally metastatic cell line by implantation of Tu167 into the tongues of nude mice and harvesting and culturing cervical lymph nodes led to production of a cell line, Tu167LN1, which was found to be anoikis-resistant. This cell line had an apoptotic cell fraction of 16.2% (+/-3.14%) after 48 h in suspension culture.

    View details for DOI 10.1016/S1368-8375(03)00049-6

    View details for Web of Science ID 000185296300003

    View details for PubMedID 12907203

  • Epidermal growth factor receptor blockade potentiates apoptosis mediated by paclitaxel and leads to prolonged survival in a murine model of oral cancer CLINICAL CANCER RESEARCH Holsinger, F. C., Doan, D. D., Jasser, S. A., Swan, E. A., Greenberg, J. S., Schiff, B. A., Bekele, B. N., Younes, M. N., BUCANA, C. D., FIDLER, I. J., Myers, J. N. 2003; 9 (8): 3183-3189

    Abstract

    Because survival for patients with oral cancer has not improved over the past 25 years, new approaches for treatment are needed. Targeted molecular therapy against epidermal growth factor receptor (EGFR) has shown promise as an adjuvant therapy in preliminary studies in several solid tumors, including head and neck cancer. The objective of this study was to determine the efficacy of paclitaxel and PKI166, a novel inhibitor of EGFR, against oral cavity cancer. Experimental Design and Results: JMAR human oral cancer cells were pretreated for 1 h with PKI166 and then stimulated with epidermal growth factor. EGFR-specific tyrosine kinase autophosphorylation measured by Western immunoblotting was inhibited by PKI166 in a dose-dependent fashion at all doses tested (0.01-1 micro M). Next, the induction of apoptosis in JMAR cells treated with paclitaxel (0.001 to 0.1 micro M) with or without PKI166 (0, 1, or 2 micro M) was determined using a propidium iodide assay. The addition of 2.0 micro M PKI166 significantly increased tumor cell death, shifting the amount of paclitaxel needed to induce apoptosis in 50% of cells from 0.1 to 0.001 micro M. These in vitro findings were confirmed using an orthotopic model of oral cancer. JMAR oral cancer cells were implanted into the tongues of nude mice. After lingual tumors developed, mice were randomized into four groups (n = 10): (a) oral PKI166 (100 mg/kg); (b) i.p. paclitaxel (200 micro g/wk); (c) PKI166 and paclitaxel; or (d) placebo. Mice treated with PKI166/paclitaxel demonstrated a significant increase in survival (P = 0.028). After necropsy, all tongue tumors were evaluated for apoptosis by the terminal deoxynucleotidyl transferase-mediated nick end labeling assay. A greater apoptotic fraction of tumor cells was found in tumors of mice treated with paclitaxel and PKI166 as compared with the other treatment groups (136.4 versus 37.8; P = 0.016).Combination therapy with paclitaxel and PKI166 prolongs survival in an orthotopic preclinical model of tongue cancer by increasing programmed cell death of oral cancer.

    View details for Web of Science ID 000184680200042

    View details for PubMedID 12912971

  • Squamous cell carcinoma of the buccal mucosa: One institution's experience with 119 previously untreated patients HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK Diaz, E. M., Holsinger, F. C., Zuniga, E. R., Roberts, D. B., Sorensen, D. M. 2003; 25 (4): 267-273

    Abstract

    Squamous cell carcinoma (SCC) of the buccal mucosa is a rare, but especially aggressive, form of oral cavity cancer, associated with a high rate of locoregional recurrence and poor survival. We reviewed our institution's experience with 119 consecutive, previously untreated patients with buccal SCC.We reviewed the charts of 250 patients who were seen at The University of Texas M. D. Anderson Cancer Center between January, 1974, and December, 1993. Of these, 119 were untreated and were subsequently treated exclusively at our institution. Patients who were previously treated elsewhere or whose lesions arose in other sites and only secondarily involved the buccal mucosa were excluded.Patients with T1- or T2-sized tumors had only a 78% and 66% 5-year survival, respectively. Muscle invasion, Stensen's duct involvement, and extracapsular spread of involved lymph nodes were all associated with decreased survival (p <.05). Surgical salvage for patients with locoregional recurrence after radiation therapy was rarely successful.SCC of the buccal mucosa is a highly aggressive form of oral cavity cancer, with a tendency to recur locoregionally. Patients with buccal mucosa SCC have a worse stage-for-stage survival rate than do patients with other oral cavity sites.

    View details for DOI 10.1002/hed.10221

    View details for Web of Science ID 000181798000002

    View details for PubMedID 12658730

  • Targeted molecular therapy for oral cancer with epidermal growth factor receptor blockade - A preliminary report ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY Myers, J. N., Holsinger, F. C., Bekele, B. N., Li, E., Jasser, S. A., Killion, J. J., FIDLER, I. J. 2002; 128 (8): 875-879

    Abstract

    Overexpression of epidermal growth factor receptor (EGF-R) is associated with increased malignant potential and correlates with poor clinical outcome in head and neck cancer. Therefore, inhibition of the EGF-R pathway provides an ideal target for molecular therapy. We examined in vitro and in vivo effects of PKI166, an orally administered EGF-R inhibitor, on 2 human squamous cell carcinoma of the oral cavity cell lines, Tu159 and MDA1986.Basic science, laboratory investigation.For Western blotting, Tu159 and MDA1986 cells were pretreated for 1 hour and then stimulated with EGF. The EGF-R-specific tyrosine kinase autophosphorylation was inhibited completely by PKI166 at all doses tested (1-10 micro g/mL). By means of a tetrazolium-based viable cell assay, PKI166 was shown to arrest the growth of Tu159 and MDA1986 cells. The inhibitory concentration (50%), calculated from regression lines on the linear portion of the growth inhibition graphs, was 0.18 micro M (R = 0.98) for Tu159 cells and 0.23 micro M (R = 0.97) for MDA1986 cells. Nude mice were inoculated subcutaneously with 1 x 10(6) Tu159 tumor cells and observed for 7 days. Next, daily doses of PKI166 (0, 10, or 50 mg/kg) were delivered by orogastric lavage for 28 days and the animals were observed for tumor growth. PKI166 significantly reduced tumor growth in mice treated for 1 month with oral PKI166 in a dose-dependent fashion.Targeted molecular therapy with EGF-R blockade arrests the growth of oral cancer in vitro and reduces its proliferation in an experimental xenograft animal model.

    View details for Web of Science ID 000177346300001

    View details for PubMedID 12162763

  • Central mucoepidermoid carcinoma of the mandible - Tumorigenesis within a keratocyst ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY Holsinger, F. C., Owens, J. M., Raymond, A. K., Myers, J. N. 2002; 128 (6): 718-720

    View details for Web of Science ID 000176264300017

    View details for PubMedID 12049571

  • An orthotopic nude mouse model of oral tongue squamous cell carcinoma CLINICAL CANCER RESEARCH Myers, J. N., Holsinger, F. C., Jasser, S. A., Bekele, B. N., FIDLER, I. J. 2002; 8 (1): 293-298

    Abstract

    Despite advances in our understanding, prevention, and treatment of head and neck squamous cell carcinoma (SCC), the 5-year survival rates for patients remain low. This poor prognosis for head and neck SCC and SCC of the oral tongue (SCCOT) in particular reflects a limited understanding of the mechanisms of local and regional metastasis, which accounts for a majority of deaths. To analyze the molecular and cellular mechanisms of metastasis, we have developed an orthotopic nude mouse model of SCCOT.Nude mice were injected submucosally in the tongue or subcutis with human squamous cell carcinoma of the oral cavity cell lines Tu159, Tu167, and MDA1986. The mice were necropsied and examined for the presence of primary tumors, and regional and systemic metastases.For all three of the squamous cell carcinoma of the oral cavity cell lines, tumors developed more readily in the orthotopic site, the tongue, than in the ectopic subcutis. MDA1986 cells were highly tumorigenic, particularly at the orthotopic site, with as few as 5 x 10(3) cells producing tumors in all of the mice. In contrast, s.c. tumor formation required at least 1 x 10(5) cells. The tumorigenicity observed between those mice given submucosal inoculation and those mice given s.c. inoculation (P < 0.0001). Regional metastases initially occurred in <10% of mice. To generate tumor lines of increased metastatic potential, regional metastases were isolated from cervical lymph nodes after the development of orthotopic tongue tumors. Serial passage of these lymph nodes resulted in a cell line more metastatic than its parental line. When injected into the tongues of mice, these cells metastasized to regional lymph nodes in 30% of mice and to the lungs in 20%.In this orthotopic murine model, oral tongue cancer recapitulates the behavior of human SCCOT, allowing for detailed studies of its biology and therapy.

    View details for Web of Science ID 000173519700042

    View details for PubMedID 11801572

  • Hearing preservation in conservation surgery for vestibular schwannoma AMERICAN JOURNAL OF OTOLOGY Holsinger, F. C., Coker, N. J., Jenkins, H. A. 2000; 21 (5): 695-700

    Abstract

    To evaluate preservation of hearing in the resection of vestibular schwannomas.A retrospective case review.Tertiary-care medical center.Forty-seven patients (25 men, 22 women) were studied; mean age was 46 years, mean tumor diameter 9.8 mm (range 3-30 mm.)All patients underwent resection of vestibular schwannomas by the middle cranial fossa (MCF) or the retrosigmoid (RS) approach.Hearing preservation was classified by the criteria outlined by the American Academy of Otolaryngology-Head Neck Surgery. Hearing was assessed preoperatively and postoperatively at 1 month and 1 year. Facial function was graded according to the House-Brackmann scale. Minimum follow-up was 18 months.Hearing was preserved in 69% of patients who underwent the MCF approach but in only 33% of patients for whom the RS approach was used. The RS approach was used for larger tumors (mean diameter 15 mm) and the MCF procedure for smaller tumors (mean diameter 9 mm). One hundred percent of patients had facial function H/B grade II or better, regardless of approach.Hearing function can be reliably preserved in a high percentage of selected patients undergoing resection of vestibular schwannoma.

    View details for Web of Science ID 000089111500020

    View details for PubMedID 10993461

  • Computer based physician education OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA Jewett, B. S., Holsinger, C., Kuppersmith, R. B., Buenting, J. E. 1998; 31 (2): 301-?

    Abstract

    Physicians are turning to computers with increasing frequency to access patients' records and laboratory values, to communicate with colleagues, and to keep current with the developments in their field. This article reviews the impact of the computers on the education of medical students and on continuing education for residents and practicing physicians. Furthermore, it emphasizes the importance and need for educating physicians about computers and the basic principles behind their development.

    View details for Web of Science ID 000073494600006

    View details for PubMedID 9518438

  • The use of e-mail by otolaryngologists ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY Kuppersmith, R. B., Holsinger, C., Jenkins, H. A. 1996; 122 (9): 921-922

    Abstract

    Electronic mail (e-mail) is an extremely powerful form of communication and the most frequently used application on the Internet. While e-mail is not the appropriate mode of communication for every situation, there are many instances where its use is invaluable.

    View details for Web of Science ID A1996VG38600001

    View details for PubMedID 8797553

  • SUCCESSFUL TREATMENT OF INVASIVE BRONCHIAL ASPERGILLOSIS AFTER SINGLE-LUNG TRANSPLANTATION CLINICAL INFECTIOUS DISEASES BIGGS, V. J., Dummer, S., Holsinger, F. C., Loyd, J. E., Christman, B. W., Frist, W. H. 1994; 18 (1): 123-124

    View details for Web of Science ID A1994MX20500026

    View details for PubMedID 8054428

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