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ABSTRACT: Objective
To investigate the effectiveness of salvage partial and total laryngectomy in the treatment of recurrent laryngeal cancer in the setting of initial nonoperative treatment failure and to identify factors influencing long-term survival.Study DesignCase series with planned chart review.SettingTertiary medical center.Subjects and Methods
Patients with recurrent squamous cell carcinoma of the larynx initially treated with either radiation or chemoradiation, who underwent salvage laryngectomy at the Cleveland Clinic Foundation from 1997 to 2011, were identified. The cohort was divided into an early-stage group and an advanced-stage group based on initial tumor staging. Survival outcome was evaluated separately in each group against tumor staging, methods of treatment, and nodal status. Secondary endpoints of speech and swallowing were also evaluated.ResultsA total of 100 patients were identified, with 72 patients in the early-stage group and 28 patients in the advanced-stage group. The overall postsalvage locoregional control rate was 70%, and the 5-year disease-specific survival was 70% and 55.2% in the early and advanced group, respectively (P = .39). The 5-year disease-specific survival was not significant in either group when compared with recurrent staging, initial treatment, salvage treatment, or nodal disease (P = ns). Using voice prostheses, good to excellent speech function was achieved postoperatively in most patients.Conclusion
Tumor staging, methods of initial and salvage treatment, and nodal disease were not significant predictors of survival. Both salvage partial and total laryngectomy were effective methods in the treatment of recurrent laryngeal cancer in carefully selected patients.
Otolaryngology Head and Neck Surgery 04/2013; · 1.72 Impact Factor
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ABSTRACT: This phase II study tested the addition of the oral epidermal growth factor receptor gefitinib to multiagent concurrent chemoradiotherapy regimen in head and neck squamous cell cancer (HNSCC).
Patients with stage III-IV HNSCC received hyperfractionated radiation (72-74.4 Gy at 120 cGy twice daily), with concurrent 96-hour infusions of cisplatin 20 mg/m(2) /day and fluorouracil 1000 mg/m(2) /day given during weeks 1 and 4. Daily gefitinib 250 mg was started on day 1 of radiation and continued for 2 years. Results were retrospectively compared with our previous study using identical chemoradiotherapy without gefitinib.
Sixty patients were enrolled in the study; 80% had stage IV disease and 68% had oropharyngeal primary tumors. The full course of gefitinib was not tolerated by 42%; there were 5 treatment-related deaths (8%). With a median follow-up of 54 months, 2- and 3-year overall survival estimates were 80% and 71%, respectively. Projected distant metastatic control at 2 and 3 years was 88%. When compared with our historical cohort, acute toxicities including renal dysfunction and unplanned rehospitalization were worse in the study patients. Projected outcome estimates did not differ between the 2 cohorts.
Addition of gefitinib to concurrent chemoradiotherapy was difficult to complete, did not improve outcomes, and increased toxicity. © 2011 Wiley Periodicals, Inc. Head Neck, 2011.
Head & Neck 12/2011; 34(11):1517-23. · 2.40 Impact Factor
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ABSTRACT: The objective of the study is to examine the utility of positron emission tomography (PET) for staging and restaging after treatment of paranasal sinus carcinomas.
Retrospective data review was done.
Patients selected underwent PET for sinonasal neoplasms from 2003 to 2008 at a tertiary care referral center.
Seventy-seven scans were reviewed from 31 patients. The pathologies included olfactory neuroblastoma (n = 9), squamous cell carcinoma (n = 6), sinonasal undifferentiated carcinoma (n = 6), sinonasal melanoma (n = 6), and minor salivary gland carcinomas (n = 4). The positive predictive value of studies performed for restaging at the primary, neck, and distant sites were 56%, 54%, and 63%; negative predictive values were 93%, 100%, and 98%, respectively. During restaging, 32% of patients were accurately upstaged secondary to neck or distant site involvement.
Positron emission tomography serves as a useful adjunct to conventional imaging in the management of sinonasal malignancies. Negative studies are effective in predicting absence of disease as seen in the consistently high-negative predictive values. Positive studies need to be viewed cautiously given the high rate of false-positive studies. When viewed in conjunction with clinical examination, endoscopic assessment, and focused biopsies, they may effectively result in a more accurate assessment of the extent of disease.
American journal of otolaryngology 09/2011; 33(3):289-95. · 0.77 Impact Factor
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ABSTRACT: T1 and T2 tonsillar squamous cell cancer with limited neck disease can be managed with single-modality radiation or surgery. Over 11 years, 17 patients underwent radical tonsillectomies; and 33 patients underwent radiation-based treatments for T1 and T2 and N0 to N2a tonsil cancer. Patients were intended to receive single-modality treatment based on presentation; however, some ultimately received adjuvant treatments.
A retrospective chart review to compare overall survival (OS), disease-specific survival (DSS), and locoregional control (LRC) between the groups was used.
In surgical group, of 17 patients, 11 underwent surgery alone, 3 underwent surgery and radiation, and 3 underwent surgery with concurrent chemoradiation. Five-year OS for the surgical and radiation groups was 93% and 72%, respectively (no significance achieved). Five-year DSS rates (93% and 80%) and LRC (69% and 89%) similarly did not yield any significant difference.
Surgery remains a viable option in the management of T1 and T2 tonsillar cancers with comparable LRC, OS, and DSS.
American journal of otolaryngology 06/2011; 33(1):98-103. · 0.77 Impact Factor
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ABSTRACT: The increased incidence of skin cancers in solid organ transplant recipients (OTR) has been well established. However, our understanding of the potential aggressive behavior of these cancers has been largely based on the findings of multiple different studies analyzing isolated indicators of aggressive behavior. The purpose of this study was to determine the aggressiveness of nonmelanotic skin cancers in a large transplant population compared with an immunocompetent control population with similar cancers.
Immunosuppressed transplanted patients and an immunocompetent control group matched in size with squamous cell carcinoma (SCC) or basal cell carcinoma (BCC) were evaluated for the factors of aggressiveness. A retrospective chart review was performed. Data obtained included transplant type, number of cancers, local recurrence rate, lymph node involvement, lymphatic invasion, perineural invasion, deep spread, subsequent treatment with radiation or chemotherapy, and death from disease.
Three hundred seven patients had SCC (OTR: 153, control: 154), and 246 patients had BCC (OTR: 123, control: 123). SCC in OTR was significantly more likely to have an increased number of primary tumors, deep tissue spread, perineural and lymphatic invasion, recurrence, and need for radiation or chemotherapy. BCC in OTR was not associated with more aggressive disease when compared with controls with BCC.
SCC in OTR behaves significantly more aggressively than in immunocompetent patients. BCC in the OTR population does not seem to act more aggressively.
Transplantation 09/2010; 90(6):683-7. · 4.00 Impact Factor
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American journal of otolaryngology 04/2010; 32(2):171-3. · 0.77 Impact Factor
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ABSTRACT: Selective reinnervation for bilateral vocal fold paralysis has been successful in animal models and shows promise in humans, but detailed, surgically relevant measurements for performing this in the human larynx are not readily available.
Anatomical study describing the anatomy and gender differences of the recurrent laryngeal nerve, with specific attention to the distance between the posterior cricoarytenoid (PCA) branch and the interarytenoid (IA) branch.
Dissection of 20 human cadaveric larynges.
The mean distance between PCA and IA branches on the left side in male specimens was 4.9 +/- 2.7 mm; on the right side 5.4 +/- 2.5 mm. The mean distance between PCA and IA branches on the left side in female specimens was 4.9 +/- 2.0 mm; on the right side 5.5 +/- 2.6 mm. A thyroid cartilage notch was required to be able to achieve sufficient access for neurorrhaphy in 57.1% of male specimens on either side and in 69.2% of female specimens on either side. The mean size of the thyroid cartilage notch required in male specimens was 39.55 +/- 19.67 mm(2), and in female specimens 47.61 +/- 12.98 mm(2).
This study provides new insight into laryngeal anatomy and further data for developing a reliable surgical approach.
The Laryngoscope 03/2010; 120(3):463-7. · 1.75 Impact Factor
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ABSTRACT: Development of a rat laryngeal transplantation model allowed for the first total human laryngeal transplantation by the senior author in 1998. In an effort to further our knowledge of the immune system's role in laryngeal rejection, a change to the mouse model was required. Prior to initiating immunosuppressive research protocols, a reliable mouse larynx rejection classification had to be established.
Animal study.
Thirty-one mouse laryngeal transplants (C57 BL/6 donors to C3H recipients) were performed and allowed to reject. Six time points were evaluated histologically: 1, 3, 5, 7, 9, and 15 days post-transplant. Eight anatomic sites were evaluated and assigned a point value. A linear regression model was constructed using the group number as the response and the scores from the eight histological criteria as predictors. Severity classifications were determined by observing patterns in the sum of scores of variables found to be significant contributors. Group 1 was normal; group 2, minimal rejection; groups 3, 4, and 5, moderate rejection; and group 6, severe rejection.
All mice survived the transplants. Of the observed histological changes, cartilage, fat, muscle, and magnitude of lymphocytic infiltration significantly correlated with rejection severity. The rejection model created demonstrated 100% accuracy in predicting the severity classification for the 31 specimens in the study.
The model established provides an accurate and reliable way to classify rejection severity in mice receiving laryngeal allografts. This sets the stage for future advanced study of manipulating the immune system as a mechanism for establishing allograft tolerance.
The Laryngoscope 10/2009; 120(1):39-43. · 1.75 Impact Factor
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ABSTRACT: The management of initially bulky nodal disease after primary nonsurgical treatment for stage IV head and neck squamous cell carcinoma (HNSCC) continues to be a subject of debate.
A retrospective chart review of neck management in patients after chemoradiation was performed.
Of the initially positive necks analyzed, 210/329 (65%) had a complete clinical response to treatment and 161 necks underwent neck surgery. Patients were pathologically positive 13.8% and 39.6% of the time after clinical complete or partial response, respectively. Regional recurrence was more frequent in necks with partial clinical (p = .04) or pathologic responses (p < .01) and with primary site recurrences (p < .01).
It is still safest at our institution to perform selective neck dissection on patients with > or = N2 neck disease when initially observed to prevent unsalvageable regional recurrence until more accurate interval assessment tools are confirmed.
Head & Neck 09/2009; 32(3):348-56. · 2.40 Impact Factor
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ABSTRACT: Certain laryngeal procedures require a sedated patient who is responsive to allow for the assessment of vocalization. Dexmedetomidine as a single agent for sedation and anxiolysis for awake laryngoplasty in a patient with unilateral vocal fold paralysis is presented.
Journal of clinical anesthesia 09/2009; 21(6):442-3. · 1.32 Impact Factor
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ABSTRACT: Laryngeal transplantation research has been studied in various animal models. For in-depth, immunology-based transplantation research, however, a thoroughly studied animal model must exist. The purpose of this study was to develop a reliable surgical technique in mice to serve as a model for further study of laryngeal transplantation.
Heterotopic laryngeal transplantation was attempted in 15 immunocompetent mice by use of modifications of previously described techniques established in rats.
Various microvascular techniques were used that led to 8 successful transplants (of 15) with patent vascularity at the time of sacrifice. The first 7 attempts at transplantation were unsuccessful because of technical difficulties related to vessel size, soft tissue traumatic injury, and venous congestion. Subsequently, 8 transplantation procedures were successfully performed after modifications of the surgical technique.
This pilot study describes the reproducible surgical techniques performed in using mice for studying laryngeal transplantation. Mice are cost-effective and immunologically well studied, and are thus ideal for further laryngeal transplantation research.
The Annals of otology, rhinology, and laryngology 07/2009; 118(6):465-8. · 1.05 Impact Factor
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ABSTRACT: Wegener granulomatosis (WG) is intimately associated with the sinonasal tract, with involvement reported in 85% of patients during the course of the disease process. The objectives of the study were: 1) to describe sinonasal symptoms and signs at the time of initial otolaryngologic evaluation; and 2) to review indications and outcomes for rhinologic surgery in WG at our institution.
A retrospective analysis of 120 patients presenting with WG and referred for otolaryngology consultation at a tertiary care center was performed.
Eighty-nine percent of patients exhibited sinonasal involvement including nasal crusting (69%), chronic rhinosinusitis (CRS) (61%), nasal obstruction (58%), bloody nasal discharge (52%), septal perforation (33%), saddle-nose deformity (23%), epiphora (13%), and mucocele formation (3.3%). Thirty-nine (33%) patients underwent primary functional endoscopic sinus surgery or dacryocystorhinotomy (DCR) prior to referral. Nineteen (16%) patients underwent noncosmetic, functional sinonasal procedures at our institution. These included endoscopic sinus surgery for CRS or mucocele decompression in 14 patients, DCR for chronic epiphora in seven patients, and orbital decompression for pseudotumor in three patients. Individual symptom recurrence within the first year was greatest for visual impairment from pseudotumor (50%), followed by CRS (14%) and nasolacrimal duct obstruction (11%).
The majority of patients with WG are referred to otolaryngology because of involvement of the sinonasal tract. Noncosmetic functional sinonasal procedures are indicated in a minority of patients. Sinonasal morbidity remains significant even after surgery. It is greatest for orbital pseudotumor, but also common for CRS and nasolacrimal duct obstruction.
The Laryngoscope 05/2009; 119(4):757-61. · 1.75 Impact Factor
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C Arturo Solares,
Benjamin Wood,
Cristina P Rodriguez, Robert R Lorenz,
Joseph Scharpf,
Jerrold Saxton,
Lisa A Rybicki,
Marshall Strome,
Ramon Esclamado,
Pierre Lavertu,
David J Adelstein
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ABSTRACT: To determine whether vocal cord fixation precludes nonsurgical management of T3/T4 laryngeal carcinoma.
A retrospective chart review.
Between 1989 and 2005 patient records with T3/T4 squamous cell carcinoma of the larynx with vocal cord fixation at presentation were reviewed. All were treated with a concomitant cisplatin-based chemoradiotherapy protocol and were part of the institutional head and neck cancer chemoradiotherapy registry. Only patients with adequate pre- and post-treatment fiberoptic evaluations were included. Charts were reviewed for demographics and tumor characteristics; return of vocal cord function; local, regional, or distant recurrence after treatment; and need for salvage surgery. The Kaplan-Meier method was used to estimate outcomes, and the log-rank test was used to compare those patients whose vocal cords remained fixed to those with recovery of function.
Twenty-three patients met the inclusion criteria, 19 males and 4 females. The median age was 59 years (range, 39-73). Fourteen patients had T3 and nine had T4 tumors. Twelve patients recovered full range of mobility, three had partial recovery, and eight did not recover motion. The median follow-up was 68 months (range, 34-191). Comparing patients with post-treatment partial or fully mobile cords to those with persistent fixation revealed the following: A projected five-year overall survival of 100% versus 25%, (P < .001), freedom from recurrence of 86.7 versus 25% (P < .001), local control without surgery of 86.7% versus 30% (P = .003), and survival with functional larynx of 86.7% versus 25% (P = .008), respectively.
Nonsurgical therapy in patients with pretreatment vocal cord fixation is feasible. However, persistence of vocal cord fixation after definitive chemoradiotherapy is a poor prognostic sign and early surgical intervention should be considered. Laryngoscope, 2009.
The Laryngoscope 05/2009; 119(6):1130-4. · 1.75 Impact Factor
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ABSTRACT: The aim of the study was to determine the prognostic impact of preepiglottic space (PES) involvement on local failure after concurrent chemoradiation therapy for squamous cell carcinoma.
Retrospective chart review of patients who underwent concurrent chemoradiation therapy for T3 or T4 laryngeal, T4 hypopharyngeal, and T3 or T4 oropharyngeal squamous cell carcinoma were eligible for inclusion. Patients were then stratified by the presence or absence of PES tumor involvement. A multivariate analysis was performed on the presence of recurrence using the following pretreatment variables: PES involvement, tumor extent, pathologic cell differentiation, lymph node involvement, age, and sex.
A total of 102 patients were included in the study. Twenty-seven (28%) patients had documented PES involvement. Mean follow-up for all patients was 46 months. Involvement of the PES was not significantly associated with local tumor persistence or recurrence (P = .69). No other variables significantly impacted tumor recurrence.
Preepiglottic space involvement does not negatively impact local tumor control after concurrent chemoradiation therapy.
American journal of otolaryngology 04/2009; 31(3):185-8. · 0.77 Impact Factor
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ABSTRACT: A 39-year-old man was referred to an endocrinology clinic for evaluation of his Cushing syndrome. He had gained 20 kg over 5 years and complained of intermittent headaches and easy bruisability. His medical history included a left foot fracture associated with minimal trauma 2 years earlier, hypertension, and stable Crohn disease with no use of exogenous glucocorticoids for at least 10 years.
Measurements of plasma adrenocorticotropic hormone, 24 h urine free cortisol excretion, late-night salivary cortisol, serum cortisol levels before and after corticotropin-releasing hormone administration during a dexamethasone suppression/corticotropin-releasing hormone-stimulation test, pituitary MRI, and inferior petrosal sinus sampling.
Cyclic Cushing syndrome secondary to an ectopic pituitary adenoma.
The cyclic nature of Cushing syndrome was suggested by the absence of hypercortisolemia during inferior petrosal sinus sampling, and was confirmed by multiple 24 h urine free cortisol measurements. The patient underwent transsphenoidal surgery, during which a 5 mm firm, round, midline sphenoid sinus lesion was identified and resected. In preoperative imaging studies, this lesion had been interpreted as being a mucosal polyp. At microscopic examination, the lesion was found to be a pituitary adenoma, which stained diffusely with antiadrenocorticotropic-hormone antibodies. Explorations of the sella and pituitary did not reveal any abnormalities. Postoperatively, the patient became hypocortisolemic and his cushingoid features resolved. His adrenal function normalized 3 months after surgery. At 18 months, the patient continued to be symptom-free with normal levels of urinary-free cortisol and midnight salivary cortisol.
Nature Clinical Practice Endocrinology & Metabolism 01/2009; 5(3):174-9. · 7.55 Impact Factor
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ABSTRACT: Head and neck squamous cell carcinoma is commonly associated with tobacco and alcohol use. There are, however, a group of patients without a significant history of tobacco or alcohol use, and the etiology of these tumors is incompletely understood.
To examine tumors in this subpopulation for association with human papillomavirus (HPV) using newly available in situ hybridization probes.
Between October 2004 and October 2005, 22 patients who did not use alcohol or tobacco were included. Formalin-fixed, paraffin-embedded tissue sections were used to perform in situ hybridization using newly available probe sets (Ventana Medical Systems, Tucson, Ariz). The slides were examined for the presence of integrated HPV using light microscopy. Positive and negative xenograft controls were run with the assay. Results.-The mean age of the patients was 64 years. There were 14 men and 8 women. The most common anatomic sites included tongue (n = 8), tonsil (n = 7), and larynx (n = 7). All cases and controls were successfully stained. Only 2 cases were positive for high-risk HPV, and both demonstrated an integrated pattern. Both cases were tumors of the tonsil. No cases were positive for low-risk HPV.
These results demonstrate that the new probe sets for HPV can be used very efficiently in clinical pathology material of head and neck squamous cell carcinoma. Our data show that high-risk HPV is an uncommon finding in head and neck squamous cell carcinoma from patients who do not have a history of tobacco or alcohol use; low-risk HPV was not seen in any case.
Archives of pathology & laboratory medicine 11/2008; 132(10):1653-6. · 2.58 Impact Factor
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ABSTRACT: Determining which patients benefit from larynx preservation strategies remains problematic. We reviewed our experience using multiagent concurrent chemoradiotherapy to identify clinical predictors for success.
Cisplatin and fluorouracil were given during weeks 1 and 4 of radiation to 115 patients with locoregionally advanced larynx or hypopharynx squamous cell cancer without cartilage invasion or laryngeal destruction. Laryngectomy was reserved for local failure.
The 5-year Kaplan-Meier projected overall survival was 58%, survival with larynx preservation 52%, local control without surgery 82%, local control (including surgical salvage) 94%, and survival with functional larynx 49%. Local control without surgery was superior in patients with T1-2 versus T3-4 tumors (97% vs 77%, p = .032). No other clinical parameters proved predictive of local control.
Larynx preservation was successful in all subsets of appropriately selected patients. Although local failure was more likely in patients with T3-4 tumors, it was infrequent and surgical salvage was effective.
Head & Neck 09/2008; 30(12):1535-42. · 2.40 Impact Factor
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Archives of otolaryngology--head & neck surgery 06/2008; 134(5):554, 556-7. · 1.92 Impact Factor
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ABSTRACT: One treatment option for unilateral vocal fold paralysis (UVFP) is ansa cervicalis-to-recurrent laryngeal nerve (ansa-RLN) anastomosis to provide reinnervation to the affected vocal fold. The advantages of this treatment approach are that it 1) provides vocal fold tone, bulk, and tension, 2) is technically simple, and 3) does not preclude other medialization procedures. We present all patients who have undergone ansa-RLN anastomosis for UVFP at our institution.
An Institutional Review Board-approved retrospective chart review was performed to include all patients who had undergone an ansa-RLN anastomosis procedure for UVFP at our institution. Data from clinical and endoscopic laryngoscopy with stroboscopy were recorded. Statistical analysis was performed on visual and perceptual vocal data.
A total of 46 patients were included in the study. Stroboscopic analysis and perceptual vocal evaluation was performed in a blinded fashion on the 21 patients who had preoperative and postoperative stroboscopy. Severity, roughness, breathiness, and strain all improved significantly over time. Glottic closure, vocal fold edge, and supraglottic effort all significantly improved after operation. Of the 38 patients with at least 3 months of follow-up, all except 1 demonstrated evidence of reinnervation.
This technique for treating UVFP results in significant improvements in patients' voice and on visual examination.
The Annals of otology, rhinology, and laryngology 02/2008; 117(1):40-5. · 1.05 Impact Factor
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ABSTRACT: The concept of human laryngeal transplantation was first introduced into the literature in the 1960s, with experiments using
the dog model by Boles, Ogura, and Silver. In 1969, Kluyskens attempted to treat a laryngeal cancer by transplantation. This
transplant was subtotal, preserving recipient perichondrium to revascularize the donor organ without the use of vascular or
neural anastomoses. The rapid recurrence of the tumor quashed interest in the procedure for nearly two decades.
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