Search

Importance: As the incidence of oropharyngeal squamous cell carcinoma (OPSCC) continues to rise in the US, an increasing number of patients are being treated with transoral robotic surgery (TORS). Readmission following surgery can potentially delay initiation of adjuvant treatment and affect survival outcomes., Objective: To identify risk factors for 30-day postoperative readmission in patients undergoing TORS for OPSCC., Design, Setting, and Participants: This retrospective, population-based cohort study used data from the Nationwide Readmissions Database from 2010 to 2017. All patients undergoing TORS for OPSCC were identified using International Classification of Diseases codes and included. Exclusion criteria were age younger than 18 years or incomplete information regarding index admission or readmission. The analysis was performed from April to October 2023., Exposure: TORS for OPSCC., Main Outcomes and Measures: Univariate and multivariate analyses were performed to determine factors associated with 30-day readmission. Covariates included demographics and medical comorbidities, socioeconomic factors, hospital characteristics, and surgical details. Trends in readmission over time, reasons for readmission, and characteristics of the readmission were also examined., Results: A weighted total of 5544 patients (mean [SD] age, 60.7 [0.25] years; 4475 [80.7%] male) underwent TORS for OPSCC. The overall readmission rate was 17.5% (n = 971), and these rates decreased over the study period (50 of 211 patients [23.7%] in 2010 vs 58 of 633 patients [9.1%] in 2017). Risk factors associated with readmission included male sex (adjusted odds ratio [AOR], 1.54; 95% CI, 1.07-2.20) and a diagnosis of congestive heart failure (AOR, 2.42; 95% CI, 1.28-4.58). Factors associated with decreased rate of readmission included undergoing concurrent selective neck dissection (AOR, 0.30; 95% CI, 0.22-0.41). Among the 971 readmissions, the most common readmission diagnoses were bleeding (151 [15.6%]), electrolyte and digestive problems (44 [4.5%]), pneumonia (44 [4.5%]), and sepsis (26 [2.7%])., Conclusions and Relevance: In this cohort study, readmission rates following TORS for oropharynx cancer decreased over time; however, a subset of patients required readmission most commonly related to bleeding, infection, and electrolyte imbalance. Concurrent neck dissection may be protective against readmission. Elucidation of risk factors for readmission after TORS for OPSCC offers opportunities for evidence-based shared decision-making, quality improvement initiatives, and improved patient counseling.

Objectives: This study investigates the impact of immediate resection of positive margins on local control of oral tongue cancer., Materials and Methods: We analyzed 273 consecutive oral tongue cancers resected from 2013 to 2018. Additional resection was performed in cases during the initial operation based on surgeon inspection of the specimen and/or frozen margins. Positive margins were defined as invasive carcinoma/high-grade dysplasia < 1 mm from the inked edge. Patients were grouped as follows: negative margin (Group 1); positive margin with immediate additional tissue resection (Group 2); and positive margin without additional tissue resection (Group 3)., Results: Overall, the rate of local recurrence was 7.7 % (21/273), and the rate of positive main specimen margin was 17.9 %. Of these patients, 38.8 % (19/49) underwent immediate additional resection of the presumed positive margin. Group 3 had higher local recurrence rates than Group 1 after adjustment for T-stage (aHR 2.8 [95 % CI 1.0-7.7], p = 0.04). Group 2 had similar rates of local recurrence (aHR 0.45 [95 % CI 0.06-3.6], p = 0.45). Three year local recurrence free survival for Groups 1, 2, and 3 were 91 %, 92 % and 73 %, respectively. Compared to the main specimen margin, sensitivity of intraoperative frozen tumor bed margins was 17.4 %, and specificity was 95 %., Conclusion: In patients with positive main specimen margins, anticipation and detection in real-time with immediate additional tissue resection reduced local recurrence to rates similar to those with negative main specimen margins. These findings support the use of technology to provide real-time intraoperative margin data and guide additional resection for improved local control., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: To identify predictors of overall survival (OS) and to stratify patients according to significant prognostic variables., Methods: A retrospective study of 274 consecutive patients with primary Oral Cavity Squamous Cell Carcinoma. Kaplan-Meier, Cox proportional hazard models, and recursive partitioning analysis (RPA) were used for analysis of OS. These results were further validated using National Cancer Database cohort of 21 895 patients., Results: Median OS was 3.65 years. T-classification and N-classification, alcoholic beverages/week, age, and adjuvant treatment were significant predictors of OS. RPA identified high-risk subpopulations: N0-1 patients with CCI ≥ 4.5 and N2-3 patients ordered by those not receiving adjuvant treatment, those with T3-4 disease despite adjuvant therapy, and those having T1-2 disease with adjuvant therapy., Conclusions: This study utilized significant prognostic indicators and RPA to highlight the importance of age, N-classification, T-classification, comorbidity, and adjuvant therapy in conjunction with American Joint Committee on Cancer staging to improve preoperative counseling., (© 2020 Wiley Periodicals LLC.)

Background: Human papillomavirus (HPV)-mediated oropharyngeal cancer (OPC) is associated with dramatically improved survival in comparison with HPV-negative OPC and can be successfully treated with surgical and nonsurgical approaches. National treatment trends for OPC were investigated with the National Cancer Data Base (NCDB)., Methods: The NCDB was reviewed for primary HPV-mediated OPC in 2010-2014. Multivariable regression was used to identify predictors of both nonsurgical therapy and receipt of adjuvant chemoradiation (CRT)., Results: There were 13,363 patients identified with a median age at diagnosis of 58 years. The incidence of triple-modality treatment (surgery with adjuvant chemotherapy) decreased from 23.7% in 2010 to 16.9% in 2014 (R 2  = 0.96), whereas the incidence of nonsurgical treatment increased from 63.9% to 68.7% (R 2  = 0.89). Hospitals in the top treatment volume quartile (quartile 1 [Q1]; n = 29) had a lower rate of positive margins (16.3%) than bottom-quartile centers (n = 741; rate of positive margins, 36.4%; P < .001); Q1 hospitals used surgical therapy significantly more. Independent predictors of nonsurgical therapy included older age, advanced disease, lower hospital volume, and living closer to the hospital or outside the Pacific United States. In surgically treated patients, younger age, lower hospital volume, nodal disease, positive surgical margins, and extranodal extension (ENE) also predicted more adjuvant CRT use., Conclusions: The use of upfront surgical treatment decreased from 2010 to 2014. Hospital volume shows a strong, inverse correlation with the rate of positive surgical margins. The upfront treatment strategy is predicted not only by staging but also by patient-, geographic-, and hospital-specific factors. Lower hospital volume remains independently associated with increased triple-modality therapy after adjustments for positive margins, ENE, and pathologic staging., (© 2019 American Cancer Society.)

Objectives: To elucidate predictive factors in the perioperative period resulting in gastrostomy tube (G-tube) dependence for patients undergoing primary surgical treatment of oropharyngeal squamous cell carcinoma (OPSCC) in the modern era., Methods: Two hundred and thirty patients with known OPSCC treated with primary surgery were screened and selected from a retrospective database spanning from 2002 to 2012 at The Ohio State University Wexner Medical Center (Columbus, Ohio), with univariable and multivariable logistic regression modeling used to determine independent predictive factors resulting in G-tube dependence (defined as tube persistence/presence 1 year after surgery)., Results: Surgical approach, baseline characteristics, tumor (T)-nodal-metastasis stage, human papillomavirus status, extent of tissue resected, surgical complications, reconstructive technique, preoperative G-tube presence, and adjuvant treatment were recorded. Patients undergoing open surgery for OPSCC without adjuvant treatment had 42.9% G-tube dependence (44.6% with adjuvant chemoradiation [CRT]) compared to 0% for those undergoing transoral nonrobotic surgery (8.1% with adjuvant CRT) and 0% for those undergoing transoral robotic surgery (10.3% with adjuvant CRT). In multivariable analysis, greater than 25% of the oral tongue resected (odds ratio [OR] 12.29; P = 0.03), an open surgical approach (OR 5.72; P < 0.01) and T3/T4 tumor stage (OR 2.84; P = 0.02) were independent and significant predictors of G-tube dependence., Conclusion: Surgical approach, advanced tumor stage, and oral tongue resection may influence the development of nutritional dependence for surgically treated patients with OPSCC., Level of Evidence: 4 Laryngoscope, 129:415-421, 2019., (© 2018 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: The purpose of this study was to illustrate the submental island flap elevation technique with simultaneous level I neck dissection followed by the inset and reconstruction of an oropharyngeal defect., Methods: A 63-year-old patient with a T2N1M0 human papillomavirus-positive squamous cell carcinoma of the tonsil was treated with concurrent chemoradiotherapy (cisplatin + 66 Gy). A local recurrence 2.5 years after treatment was treated surgically and reconstructed with a submental island flap., Results: There were no complications and oral diet was initiated at 2 weeks and the gastrostomy tube was removed 1 month postoperatively. A video demonstration of the submental island flap elevation is included with a focus on how levels 1A and 1B can be dissected safely and this can be viewed online on Head & Neck's home page at http://onlinelibrary.wiley.com/., Conclusion: The submental island flap can be performed safely with a level I neck dissection for head and neck reconstruction., (© 2018 Wiley Periodicals, Inc.)

Objectives: to examine the impact of radiotherapy center volume on overall survival in patients with oral cavity and oropharyngeal squamous cell carcinoma getting adjuvant radiation therapy after receiving surgery at a high-volume center., Materials and Methods: a retrospective study was conducted on patients with oral cavity squamous cell carcinoma or oropharyngeal squamous cell carcinoma treated surgically at a tertiary institution from 2000 to 2012 who received adjuvant radiotherapy. The outcome variable was overall survival and the independent variable was location of adjuvant radiation therapy: high-volume center (HVC) versus low-volume center (LVC). Cox proportional hazards models were used to assess associations between predictors of death. Variables that were found to be significant at the α = 0.10 were included in a multivariable model., Results: 336 patients met inclusion criteria. One-hundred thirty-nine patients received adjuvant radiation therapy at HVC and 197 patients received adjuvant radiation therapy at LVC. A univariate Cox proportional hazards model identified the variables location, age, marital status, subsite, T stage, extracapsular extension, and smoking status to include in a multivariable model. Age, subsite, T stage, and extracapsular extension were independent predictors of overall survival (p < .05). Location (p = .55), marital status (p = .29), and smoking status (p = .22) were not statistically significant predictors of survival., Conclusion: After surgery at a HVC, the volume of adjuvant radiation therapy center was not significantly associated with overall survival. Significant predictors of survival included age, subsite, T stage, and extracapsular extension., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: The purpose of this study is to determine the incidence and risk factors for bilateral tonsillar cancers treated with transoral robotic surgery (TORS) and to determine the morbidity of the procedure., Methods: Patients undergoing TORS for known tonsillar cancer were retrospectively reviewed. Perioperative variables and surgical outcomes were analyzed to determine predictive factors for bilateral disease and morbidity rates., Results: Seventy-nine consecutive patients with tonsillar cancers underwent primary TORS radical tonsillectomy. Thirty of these patients also underwent contralateral tonsillectomy. Three patients (10%) were found to have contralateral tonsillar cancers on final pathology. These were not identified on preoperative positron emission tomography (PET)-CT or clinical examination. There were no differences in complications, gastrostomy tube (G-tube) rates, or length of stay (P > .05). Blood loss was 11.5 cc more in the contralateral tonsillectomy group (P = .001)., Conclusion: All patients undergoing primary TORS for tonsillar cancers should also undergo contralateral tonsillectomy to optimize oncologic outcomes with no increase in morbidity., (© 2017 Wiley Periodicals, Inc.)

Background: Computer-guided 3D virtual planning and customized templates are novel and effective methods aiding maxillary reconstruction, particularly during osteocutaneous free tissue transfer of complex defects. However, virtual planning and modelling is often expensive., Methods: We present a new method to reconstruct complex defects with a surgical stent designed from presurgical casts. We present 2 patients who underwent this technique. Reconstruction in both cases was aided by a surgical stent fashioned preoperatively to approximate the anatomic dimensions of the defect, guiding the shape and orientation of the flap during inset to aid in dental rehabilitation., Results: Surgery was performed without evidence of malocclusion, oronasal separation, or osteoradionecrosis with both patients undergoing successful rehabilitation and showing good postoperative oral intake., Conclusion: Utilization of our novel surgical stent allowed reconstruction of complex maxillectomy defects and facilitated the design of a reconstructive flap without the need of pre-bent plates, cutting guides, or associated expenses., (© 2017 Wiley Periodicals, Inc.)

Objectives The Notch1 signaling pathway has recently been shown to be highly dysregulated in head and neck squamous cell carcinoma, but the value of Notch1 as a predictive biomarker is yet to be elucidated in oropharyngeal squamous cell carcinoma (OPSCC). The objective of this study is to evaluate Notch1 expression in surgical OPSCC specimens and determine clinicopathologic correlates. Study Design Case series with planned data collection. Setting Tertiary academic medical center. Subjects and Methods Surgical specimens from 181 patients with OPSCC were collected to create a tissue microarray (TMA). Human papillomavirus (HPV) status and Notch1 expression were determined and correlated with clinicopathologic characteristics. Results In univariate analysis, Notch1 expression correlated with improved survival as a categorical variable (hazard ratio [HR], 0.346; P < .0001) and correlated with HPV/p16 positivity as a continuous variable ( P < .0001). In multivariate analysis, Notch1 expression retained significance in HPV-positive (HR, 0.303; P = .033) and HPV-negative (HR, 0.416; P = .0055) subgroups. Similarly, Notch1 expression positively correlated with survival in p16-positive (HR, 0.469; P = .031) and p16-negative subgroups (HR, 0.310; P = .014). Conclusions In the largest OPSCC cohort to date, we found that Notch1 receptor expression positively correlates with overall survival, regardless of HPV or p16 status. Furthermore, we found higher Notch1 receptor expression in HPV/p16-positive tumors than their HPV/p16-negative counterparts.

We report imaging findings of a 64-year-old male patient with a ruptured epidermoid cyst (EC) known to be constant over the 23-year follow-up and showing malignant transformation to squamous cell carcinoma (SCC). Computed tomography (CT) and magnetic resonance imaging (MRI) findings including diffusion weighted imaging (DWI), 1H+MR spectroscopy (MRS), dynamic susceptibility contrast perfusion (DSC) MRI of EC, and its rare complications are presented together with a review of the literature. Fluid-lowattenuated- inversion-recovery (FLAIR) and T1-weighted images with gadolinium are the best sequences together with DWI to show the relationship of the EC, the SCC and the border between. Primary brain SCC enhances mostly ring-like or peripherally, but diffuse enhancement is also possible. To our knowledge, no MRS and DSC findings have been reported in the literature yet.

Objectives: The incidence of human papillomavirus (HPV) positive oral squamous cell carcinoma (OSCC) continues to increase over time, challenging healthcare providers to address their patients' HPV-related concerns., Materials and Methods: This prospective study assessed health literacy, HPV knowledge, utilization and trust in information sources among patients with incident HPV-positive or HPV-negative OSCC diagnosed at the Ohio State University from 2011 to 2015. Health literacy was assessed with a standardized scale. Additional questions evaluated HPV knowledge (including transmission, prevalence, health consequences and treatment), the frequency and type of information sources sought, and trust in those sources., Results: Surveys were collected from 372 OSCC cases (HPV-positive, n=188; HPV-negative, n=184). Despite high mean health literacy scores, only 45.2% of HPV-related knowledge questions were answered correctly. HPV was known to be a sexually transmitted infection and a cause of cervical and anal cancer by 66.0%, 56.5% and 15.2%, respectively. In all domains, cases with HPV-positive OSCC were significantly more informed than HPV-negative cases (for all, p<0.01). Only 52.7% and 56.2% of patients with HPV-positive OSCC felt they knew enough to be comfortable discussing HPV with their doctor or sexual partner, respectively. The most frequently used information source was the internet (80.9%), which ranked 8th in trust of 15 possible sources. Although most (95.5%) patients trusted information from their doctors, only 37.9% used doctors as an information source., Conclusions: Doctors are a highly trusted, but infrequent utilized, information source and should facilitate patient access to high-quality HPV information sources., (Copyright © 2016. Published by Elsevier Ltd.)

Chronic sclerosing sialadenitis (CSS) is a benign chronic inflammatory condition of the salivary gland. Clinically, CSS patients may present with a neck mass, often suggesting a neoplastic process. Fine-needle aspiration (FNA) is frequently used to evaluate these lesions. We present a series of 4 patients with CSS, in whom all but one had history of squamous cell carcinoma. The previous diagnosis of malignancy appeared to influence the interpretation of the cytologic preparations. Four patients who had undergone resection of a neck nodule that eventually was diagnosed as CSS were identified. FNA was performed in all 4 cases, and the final cytologic diagnosis in these cases included squamous cell carcinoma, basaloid neoplasm, and salivary gland neoplasm. During intraoperative consultation, the lesions were identified as benign, atrophic salivary gland with chronic inflammation, or sialadenitis with atypical glands. All resected specimens were submitted for histopathological examination and were considered diagnostic for CSS. CSS is a potential pitfall in the FNA interpretation of salivary gland lesions, especially if there is a previous history of head and neck malignancy. Awareness of this entity, adherence to strict cytologic criteria, and careful clinicopathologic correlation are helpful in preventing misinterpretation and unnecessary surgical intervention.

Myoferlin (MYOF) is a member of ferlin family of membrane proteins that was originally discovered as a muscle specific protein. Recent studies have shown that myoferlin is also expressed in other cell types including endothelial cells and cancer cells. However, very little is known about the expression and biological role of myoferlin in head and neck cancer. In this study, we examined expression profile of myoferlin in oropharyngeal squamous cell carcinoma (OPSCC) and assessed its correlation with disease progression and patient outcome. In univariate analyses, nuclear MYOF was associated with poor overall survival (p<0.001) and these patients had 5.5 times increased hazard of death (95% Cl 3.4-8.8). Nuclear myoferlin expression was also directly associated with tumor recurrence (p<0.001), perineural invasion (p=0.008), extracapsular spread (p=0.009), higher T-stage (p=0.0015) and distant metastasis (p<0.001). In addition, nuclear MYOF expression was directly associated with IL-6 (p<0.001) and inversely with HPV status (p=0.0014). In a subgroup survival analysis, MYOF nuclear+/IL-6+ group had worst survival (84.6% mortality), whereas MYOF nuclear-/IL-6- had the best survival. Similarly, patients with HPV-negative/MYOF-positive tumors had worse survival compared to HPV-positive/MYOF-negative. Taken together, our results demonstrate for the first time that nuclear myoferlin expression independently predicts poor clinical outcome in OPSCC patients.

Background: The literature is scarce regarding transoral robotic surgery (TORS) with simultaneous neck dissection. This study evaluates the safety and efficacy of concurrent neck dissection in oropharyngeal squamous cell carcinoma (SCC) treated with TORS., Methods: Analysis of 113 patients with oropharyngeal SCC treated with TORS and concurrent neck dissection., Results: Six intraoperative communications between the pharynx and neck region were recognized. After pharyngeal mucosal flap advancement, 1 defect was closed primarily and another one was reinforced with acellular dermal matrix. In 1 case, submandibular gland was transposed posteriorly over the sutured defect as a support. One omohyoid and 2 digastric muscular pedicle rotation flaps were used in the remaining 3 patients for the reconstruction of pharyngeal communications. None of the patients developed postoperative pharyngocutaneous fistula., Conclusion: The advantage of TORS oropharyngectomy, when compared with open approaches, is the avoidance of pharyngocutaneous fistula even in the presence of concurrent neck dissection © 2015 Wiley Periodicals, Inc. Head Neck 38: E519-E523, 2016., (© 2015 Wiley Periodicals, Inc.)

Background: The purpose of this study was to further define the impact of primary surgery in the management of oropharyngeal squamous cell carcinoma (SCC)., Methods: Two hundred ninety-six patients with oropharyngeal SCC treated with primary surgery were included. Multivariable analysis and recursive partitioning analysis (RPA) identified predictors of survival and gastrostomy tube presence., Results: Multivariable analysis identified that HPV negativity (p = .0002), presence of extranodal extension (p = .0025), and advanced T classification (p = .0081) were independent predictors of survival. For HPV-positive patients, surgical approach (p = .0111) and margin status (p = .0287) were significant predictors of survival. For HPV-negative patients, extranodal extension (p = .0021) and advanced T classification (p = .0342) were significant predictors of survival. Smoking status and advanced neck disease did not impact survival, and the addition of adjuvant chemotherapy did not confer survival benefit in HPV-positive or HPV-negative subgroups., Conclusion: Independent predictors of survival are unique in patients with oropharyngeal SCC treated with primary surgery. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1794-E1802, 2016., (© 2015 Wiley Periodicals, Inc.)

Black raspberries (BRB) demonstrate potent inhibition of aerodigestive tract carcinogenesis in animal models. However, translational clinical trials evaluating the ability of BRB phytochemicals to impact molecular biomarkers in the oral mucosa remain limited. The present phase 0 study addresses a fundamental question for oral cancer food-based prevention: Do BRB phytochemicals successfully reach the targeted oral tissues and reduce proinflammatory and antiapoptotic gene expression profiles? Patients with biopsy-confirmed oral squamous cell carcinomas (OSCC) administered oral troches containing freeze-dried BRB powder from the time of enrollment to the date of curative intent surgery (13.9 ± 1.27 days). Transcriptional biomarkers were evaluated in patient-matched OSCCs and noninvolved high at-risk mucosa (HARM) for BRB-associated changes. Significant expression differences between baseline OSCC and HARM tissues were confirmed using a panel of genes commonly deregulated during oral carcinogenesis. Following BRB troche administration, the expression of prosurvival genes (AURKA, BIRC5, EGFR) and proinflammatory genes (NFKB1, PTGS2) were significantly reduced. There were no BRB-associated grade 3-4 toxicities or adverse events, and 79.2% (N = 30) of patients successfully completed the study with high levels of compliance (97.2%). The BRB phytochemicals cyanidin-3-rutinoside and cyanidin-3-xylosylrutinoside were detected in all OSCC tissues analyzed, demonstrating that bioactive components were successfully reaching targeted OSCC tissues. We confirmed that hallmark antiapoptotic and proinflammatory molecular biomarkers were overexpressed in OSCCs and that their gene expression was significantly reduced following BRB troche administration. As these molecular biomarkers are fundamental to oral carcinogenesis and are modifiable, they may represent emerging biomarkers of molecular efficacy for BRB-mediated oral cancer chemoprevention., (©2015 American Association for Cancer Research.)

Multiple diagnostic and treatment paradigms exist for the management of carcinoma of unknown primary (CUP) metastatic to cervical lymph nodes. Transoral robotic surgery (TORS) has emerged as a modality for diagnosis and treatment of CUP, optimizing identification and resection of the primary tumor, although also preventing chemotherapy in a subset of patients. This article presents the authors' treatment paradigm and reviews the literature supporting the use of TORS in the management of CUP., (© 2015 Wiley Periodicals, Inc.)

Transoral robotic surgery (TORS) is increasingly used in laryngeal/hypopharyngeal cancer surgery. Ablative procedures described in these anatomical sites include: (i) supraglottic laryngectomy, (ii) total laryngectomy, (iii) glottic cordectomy, and (iv) partial pharyngectomy. TORS supraglottic laryngectomy remains the most commonly performed of these procedures. Initial oncologic and functional outcomes with these procedures are promising and comparable to other treatment options. As robotic instrumentation technology advances a rise in TORS laryngeal/hypopharyngeal surgery is anticipated., (© 2015 Wiley Periodicals, Inc.)

Early stage oropharyngeal squamous cell carcinoma (OPSCC) may occasionally invade parapharyngeal space (PPS). Tumor invasion of PPS structures such as the carotid artery, internal jugular vein and cranial nerves IX-XII may add significant morbidity. We analyzed 73 patients who underwent transoral robotic surgery (TORS) for OPSCC between 2008 and 2012. Patients were selected based on preoperative evaluation including detailed physical and endoscopic examination, neck CT and/or PET-CT scan. T1, T2 and selected T3 cases were included in this study. None of the patients had obvious PPS extension on preoperative evaluation. All patients had OPSCC in palatine tonsil (60; 82.2 %) and base of tongue (13; 17.8 %). Twenty-seven patients had cT1 (37 %), 39 had cT2 (53.4 %), and 7 had cT3 (9.6 %) disease in clinical and radiologic evaluation. None of the oropharyngeal lesions had obvious radiologic PPS extension prior to operation. During TORS procedure, we encountered PPS in 18 (24.6 %) patients while resecting the deep margin. These parapharynx resections involved external carotid artery in 1, medial pterygoid muscle in 2, and parapharyngeal fat with or without styloid musculature in the remaining 15 patients. Except three cases, we were able to remove the lesions en bloc with negative surgical margins. TORS resection of oropharyngeal cancer extending to PPS appears to be a safe and feasible technique with minimal complications. Significant experience with TORS and further understanding of the endoscopic anatomy of PPS could obviate the morbidity associated with tumor resection in this dense neurovascular region.

Background: Transoral robotic surgery (TORS) has been used as a novel procedure for the resection of laryngopharyngeal cancers with promising outcomes. There are several studies proposing the benefit of combining TORS with a carbon dioxide (CO2 ) laser in resecting upper aerodigestive tract tumors. The purpose of this study was to illustrate transoral robot-assisted carbon dioxide laser surgery (TORS-L) for hypopharyngeal cancers., Methods: A 59-year-old patient with T1N0M0 cancer at the lateral hypopharyngeal wall was selected for TORS-L., Results: Tumor was excised in 1 piece with adequate surgical margins. There was no perioperative complication. The patient was extubated immediately after surgery. Oral diet was initiated within the first 24 hours. No gastrostomy or tracheostomy tube placement was required. A video demonstration of TORS-L is included, which can be viewed online on Head & Neck's home page at http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1097-0347., Conclusion: TORS-L hypopharyngectomy is a safe and feasible procedure for the resection of selected hypopharyngeal tumors., (© 2015 Wiley Periodicals, Inc.)

Transoral robotic surgery (TORS) has been used as a novel procedure for squamous cell carcinoma of the laryngopharyngeal cancers with encouraging outcomes. The safety, feasibility, and efficacy regarding this approach have previously been demonstrated. There are several studies proposing the benefit of combining TORS with carbon dioxide (CO2) laser in resecting upper aerodigestive tract tumors. We report a series of patients with hypopharyngeal carcinoma treated with primary TORS with or without the flexible carbon dioxide (CO2) laser. All TORS resections were completed without any intraoperative complication. None required conversion to an open procedure. Clinical outcomes in this preliminary analysis indicate that magnified view, 3D visualization with the wristed instruments and tremor reduction technology of robotic experience, allow en bloc resection of early stage hypopharyngeal cancers. TORS with CO2 laser is a promising, minimally invasive surgical alternative for the treatment of hypopharyngeal tumors with comparable oncologic outcomes.

Background: Transoral robotic surgery (TORS) has emerged as a novel, safe, and feasible procedure for the resection of supraglottic laryngeal cancers. The purpose of this study was to demonstrate the surgical technique for TORS supraglottic laryngectomy (SGL)., Methods: A patient with a T2N0M0 laryngeal cancer limited to the supraglottic larynx was selected for TORS., Results: En bloc tumor resection was accomplished with negative surgical margins together with bilateral selective neck dissection. There was no perioperative or early postoperative complication. The patient was extubated immediately after surgery. Oral supraglottic diet was initiated within the first 24 hours. No gastrostomy or tracheostomy tube placement was required. A video demonstration of the surgical technique is included on Head & Neck's website., Conclusion: TORS SGL is a safe and feasible procedure for the resection of selected supraglottic tumors., (© 2014 Wiley Periodicals, Inc.)

Objectives/hypothesis: To determine speech, eating, aesthetics, social disruption, and overall quality-of-life outcomes over a year period in patients who underwent transoral robotic surgery as part of carcinoma of unknown primary diagnosis and treatment., Study Design: Observational prospective study., Methods: Twenty-two patients who underwent transoral robotic surgery for the management of carcinoma of unknown primary were included. Patients prospectively completed the Head and Neck Cancer Inventory during a preoperative visit, and at 3-week, 3-month, 6-month, and 12-month postoperative visits. Patients' demographic, pathological, and follow-up information were also collected., Results: The mean follow-up time was 19.8 months. There were overall declines in all quality of life scores during treatment period, which was followed by a continuous recovery. The scores immediately after transoral robotic surgery (3 weeks) were significantly higher than the scores after conclusion of adjuvant therapy (3 months) in multiple domains (P < .05) and the 6-month scores in speech (P = .02) and eating (P = .008) domains. All scores, except for eating (P = .01) returned to pretreatment levels at 1 year. Patients with detected primaries displayed similar quality-of-life scores compared to patients with occult primaries. Human papillomavirus status and type of adjuvant treatment had no significant impact on quality of life., Conclusions: Transoral robotic surgery is a promising, minimally invasive procedure for the surgical management of carcinoma of unknown primary. Patients maintain high functional and quality-of-life status at 1 year after surgery., (© 2014 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: The management of carcinoma of unknown primary (CUP) is one of the challenging conditions in head and neck oncologic surgery. Despite various diagnostic tools, the primary tumor site in more than half of cases remains unidentified. The purpose of this study was to assess the feasibility and efficiency of utilizing transoral robotic surgery (TORS) for the diagnosis and treatment of CUP in the head and neck., Methods: In this prospective, single-institutional, clinical TORS trial, 22 of 181 patients were treated for CUP between 2008 and 2012., Results: Among all those 22 patients, primary tumor site identification and complete tumor removal was achieved in 17 patients (77.3%) with TORS. Tonsil (59.1%) and base of tongue (18.1%) were identified as the most common tumor locations., Conclusion: Together with panendoscopy, directed biopsies, and positron emission tomography (PET)/CT, TORS is a valuable option in the identification and treatment of primary tumor sites., (© 2013 Wiley Periodicals, Inc.)

Background: Human papillomavirus 16 (HPV16) is a major risk factor for the development of head and neck squamous cell carcinoma (HNSCC), particularly the development of oropharyngeal squamous cell carcinoma (OPSCC). Cancer stem cells (CSCs) are resistant to conventional therapies, and it is postulated that they are responsible for disease recurrence and/or progression. Because the prognoses of patients with HPV16-positive and HPV-negative HNSCC are distinct, the authors sought to determine whether differences in the number of CSCs could account for this clinical observation., Methods: CSC populations in HPV16-positive and HPV-negative HNSCC were assessed using a proprietary assay based on expression of the enzyme aldehyde dehydrogenase (ALDH), an in vitro tumorsphere formation assay, and an in vivo limiting cell dilution in nonobese diabetic/severe combined immunodeficiency mice. A high-density tissue microarray was stained with ALDH1, a CSC marker, to determine the association between CSCs and HPV16-positive/HPV-negative OPSCC., Results: HPV16-positive HNSCC had a greater intrinsic CSC pool than HPV-negative HNSCC. Inactivation of p53 has been identified as a major mechanism for the elevated CSC population in HPV16-positive HNSCC. In vivo limiting cell dilution experiments using tumors from patients with HPV16-positive and HPV-negative OPSCC indicated that the CSC frequency was 62.5-fold greater in an HPV16-positive OPSCC tumor than in an HPV-negative OPSCC tumor. Primary tumors from patients with HPV16-positive OPSCC were associated with elevated tumor ALDH1 staining, further extending the association between HPV16 and CSCs., Conclusions: The current data and the clinical observation that patients with HPV16-positive HNSCC respond more favorably to current treatment paradigms than patients with HPV-negative HNSCC support the suggestion that CSC phenotype is not homogeneous. Therefore, the reliance on the CSC number may be insufficient to accurately assess the potential of a particular tumor for disease recurrence and/or progression., (© 2013 American Cancer Society.)

The retromolar trigone is a challenging transoral surgical site due to the difficulty of visualization. Our aim is to report a new technique of transoral robotic resection of retromolar trigone tumours. We present three patients with retromolar trigone tumours with pathological diagnosis of squamous cell carcinoma who underwent successful transoral robotic resection. Robotic retromolar trigone resection and concurrent supraomohyoid neck dissections were performed in all patients without any complication. In conclusion, transoral robotic surgery is a safe and feasible technique for resection of malignant retromolar trigone tumours with minimal complications and favourable outcomes.

Importance: Because treatment for oropharyngeal squamous cell carcinoma (OPSCC), especially in patients of older age, is associated with decreased patient quality of life (QOL) after surgery, demonstration of a less QOL-impairing treatment technique would improve patient satisfaction substantially., Objective: To determine swallowing, speech, and QOL outcomes following transoral robotic surgery (TORS) for OPSCC., Design, Participants, and Setting: This prospective cohort study of 81 patients with previously untreated OPSCC was conducted at a tertiary care academic comprehensive cancer center., Interventions: Primary surgical resection via TORS and neck dissection as indicated., Main Outcomes and Measures: Patients were asked to complete the Head and Neck Cancer Inventory (HNCI) preoperatively and at 3 weeks as well as 3, 6, and 12 months postoperatively. Swallowing ability was assessed by independence from a gastrostomy tube (G-tube). Clinicopathologic and follow-up data were also collected., Results: Mean follow-up time was 22.7 months. The HNCI response rates at 3 weeks and 3, 6, and 12 months were 79%, 60%, 63%, and 67% respectively. There were overall declines in speech, eating, aesthetic, social, and overall QOL domains in the early postoperative periods. However, at 1 year post TORS, scores for aesthetic, social, and overall QOL remained high. Radiation therapy was negatively correlated with multiple QOL domains (P < .05 for all comparisons), while age older than 55 years correlated with lower speech and aesthetic scores (P < .05 for both). Human papillomavirus status did not correlate with any QOL domain. G-tube rates at 6 and 12 months were 24% and 9%, respectively. Greater extent of TORS (>1 oropharyngeal site resected) and age older than 55 years predicted the need for a G-tube at any point after TORS (P < .05 for both)., Conclusions and Relevance: Patients with OPSCC treated with TORS maintain a high QOL at 1 year after surgery. Adjuvant treatment and older age tend to decrease QOL. Patients meeting these criteria should be counseled appropriately.

Objective: Although the majority of human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinomas have a favorable prognosis, we search for markers of poor prognosis by carefully examining a subset of highly aggressive cases., Study Design: Seven patients with HPV-positive oropharyngeal cancer who presented with non-pulmonary distant metastasis or developed distant metastasis posttreatment were identified. Eight control cases were chosen which responded well to treatment. Pathologic and radiologic studies were reviewed and compared., Results: Two cases displayed a small cell carcinoma (SmCC) component upon pathologic review. Biomarker analysis revealed lower expression of NOTCH1 in the aggressive cohort in comparison to controls (P = .04). Cases showed a predominance of clustering of lymph nodes, extracapsular spread, and central tumor necrosis., Conclusion: Although most HPV-related oropharyngeal cancers display a positive prognosis, it is evident that there is a subset, which behaves more aggressively. This early investigation identifies pathologic and radiologic features that may help to predict this behavior., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Transoral, minimally invasive organ preservation surgeries are being increasingly used for laryngopharyngeal carcinomas to avoid the toxicities of combined chemotherapy and radiation therapy regimens. This study investigates the efficiency, safety, and functional outcomes of transoral robotic surgery (TORS) supraglottic laryngectomy., Methods: Patients with laryngeal cancer who underwent TORS supraglottic laryngectomy and participated in a prospective TORS study between 2008 and 2011 at an academic medical center are presented., Results: Thirteen of 126 patients underwent TORS supraglottic laryngectomy for laryngeal cancer. Average robotic operative time and estimated blood loss were 25.3 minutes and 15.4 mL, respectively. Negative surgical margins were achieved in all patients. Eleven patients were started on an oral diet within 24 hours of surgery with no evidence of immediate airway compromise. Two patients (15.4%) received adjuvant radiation therapy based on pathology., Conclusion: In this preliminary study, TORS supraglottic laryngectomy was a safe procedure with good functional outcomes., (Copyright © 2012 Wiley Periodicals, Inc.)

Background: Although positron emission tomography computed tomography has proven diagnostic and staging value in head and neck carcinoma, it does not have optimal sensitivity or specificity. The positron emission tomography computed tomography fluorodeoxyglucose standardised uptake value has been shown to be associated with carcinoma stage. This study evaluated the impact of major clinicopathological factors on the standardised uptake value at the primary site and at neck lymph node metastases., Subjects and Methods: Two hundred and forty-three oral cavity and laryngopharyngeal carcinoma patients who underwent positron emission tomography computed tomography were included. Correlation between the positron emission tomography computed tomography standardised uptake value and various clinicopathological factors was analysed., Results: A positive correlation was found between the standardised uptake value and the size and depth of tumour infiltration, and lymph node positivity. Higher standardised uptake values were seen for more advanced tumour stages. The presence of perineural invasion, lymphatic invasion and extracapsular spread were all associated with increased standardised uptake values., Conclusion: Most of the clinicopathological features of head and neck carcinoma which are well known to be poor prognostic factors have a significant impact on positron emission tomography computed tomography fluorodeoxyglucose standardised uptake value.

Larynx cancer is the commonest malignancy of upper aerodigestive tract. However, laryngeal cancer is extremely rare in childhood since these tumors are generally not suspected in the differential diagnosis of hoarseness, dysphagia and/or progressive airway obstruction in children; diagnosis can be made relatively late. In this report we would like to present a case of advanced stage pediatric laryngeal carcinoma who was treated with chemoradiotherapy and remained well on her 5-year follow-up., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

The aim was to evaluate the efficacy of [(18)F]-2-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) in evaluating metastasis of head and neck squamous cell carcinoma (HNSCC) to the cervical lymph nodes, with specific attention to the efficacy in regard to clinically negative necks. This was a retrospective review of 243 patients with HNSCC between years 2005 and 2007 treated at a comprehensive cancer care institution who underwent pre-operative PET/CT and neck dissection with either an N0 (112 patients) or N+ (131 patients) clinical nodal status. PET/CT findings were correlated with histopathological results of surgical specimens. A majority of the primary sites were oral cavity and oropharynx (70%), followed by larynx, unknown primary and hypopharynx. In the group of 112 patients who underwent 144 neck dissections with N0 nodal status, sensitivity, specificity, positive predictive value (PPV) and negative predictive (NPV) and accuracy were 57, 82, 59, 80 and 74%, respectively. In the group of 131 patients who underwent 169 neck dissections with N+ nodal status, sensitivity, specificity, PPV, NPV and accuracy were 93, 70, 96, 58 and 91%, respectively. PET/CT has a much reduced rate of efficacy for the clinically negative neck compared to the clinically positive neck. PET/CT in its current stage does not appear to offer an advantage in staging the clinically N0 neck due to high rates of false positives and negatives.

Objective: To identify specific alcohol-related predictors of postoperative delirium., Design: Inception cohort, logistic regression with step-wise selection., Setting: Ohio State University Comprehensive Cancer Center, Columbus., Patients: A total of 774 patients undergoing major resection of head and neck squamous cell carcinoma., Main Outcome Measures: The correlation of 19 variables with postoperative delirium. One variable was an alcohol-related blood test: mean red blood cell volume (MCV). Eight variables were patient responses to alcohol-related questions., Results: Eighty-nine of 774 surgical procedures (11.5%) were complicated by delirium. Six variables were significantly associated with delirium: age older than 69 years (odds ratio [OR], 2.43; P < .01), preexisting cognitive impairment (OR, 3.83; P < .01), surgery duration greater than 6 hours (OR, 2.40; P < .01), MCV greater than 95.0 femtoliters (OR, 2.23; P < .01), ever being advised to cut back on alcohol (OR, 2.25; P = .01), and not abstaining from alcohol for at least 1 continuous week in the preceding year (OR, 2.16; P = .02). The number of variables stratified delirium risk (0 variables: 198 patients, 2.5% incidence of delirium; 1 variable: 278 patients, 6% incidence of delirium; 2 variables: 206 patients, 18% incidence of delirium; and >2 variables: 92 patients, 34% incidence of delirium)., Conclusions: Three clinical variables not related to alcohol drinking (age, preexisting cognitive impairment, and surgery duration), an alcohol-related laboratory test (MCV), and 2 alcohol-related questions ("At any time in your life, has anyone ever suggested that you should cut back on your drinking?" and "What is the greatest number of days in a row you have gone without an alcoholic drink in the past year?") may help in estimating a patient's risk for postoperative delirium.

Epithelial to mesenchymal transition (EMT) has been hypothesized as a mechanism by which cells change phenotype during carcinogenesis, as well as tumor metastasis. Whether EMT is involved in cancer metastasis has a specific, practical impact on the field of circulating tumor cells (CTCs). Since the generally accepted definition of a CTC includes the expression of epithelial surface markers, such as EpCAM, if a cancer cell loses its epithelial surface markers (which is suggested in EMT), it will not be separated and/or identified as a CTC. We have developed, and previously reported on the use of, a purely negative enrichment technology enriching for CTCs in the blood of squamous cell carcinoma of the head and neck (SCCHN). This methodology does not depend on the expression of surface epithelial markers. Using this technology, our initial data on SCCHN patient blood indicates that the presence of CTCs correlates with worse disease-free survival. Since our enrichment is not dependent on epithelial markers, we have initiated investigation of the presence of mesenchymal markers in these CTC cells to include analysis of: vimentin, epidermal growth factor receptor, N-cadherin, and CD44. With the aid of confocal microscopy, we have demonstrated not only presumed CTCs that express and/or contain: a nucleus, cytokeratins, vimentin, and either EGFR, CD44, or N-cadherin, but also cells that contain all of the aforementioned proteins except cytokeratins, suggesting that the cells have undergone the EMT process. We suggest that our negative depletion enrichment methodology provides a more objective approach in identifying and evaluating CTCs, as opposed to positive selection approaches, as it is not subjective to a selection bias and can be tailored to accommodate a variety of cytoplasmic and surface markers which can be evaluated to identify a multitude of phenotypic patterns within CTCs from individual patients, including so-called EMT as presented here.

Objective: To report a single institution's experience with transoral robotic surgery (TORS) and its clinical outcomes., Study Design: Preliminary clinical data from a prospective TORS study., Setting: University tertiary care facility., Subjects and Methods: Patients who underwent TORS at The Ohio State University Medical Center. Demographic, intraoperative, clinicopathological, and follow-up functional data were collected., Results: Sixty-four patients underwent TORS with a median age of 56.9 years. A total of 113 TORS procedures were performed. Fifty-four patients with squamous cell cancer (SCCA) were included in the final analysis. Mean follow-up time was 11.8 months (range, 2-29). There was a trend toward longer TORS setup time, operative time, estimated blood loss, and hospital length of stay with advanced (T(3)) compared with early-stage tumors (T(1-2)). There were no major intraoperative complications, and none of the procedures were aborted because of inability to remove the tumor. Negative resection margins were achieved in 93% of cases of SCCA. No patients experienced immediate postoperative complications, and all of the patients tolerated an oral diet without any airway compromise on the day of surgery. Forty-nine patients (91%) underwent adjuvant radiation therapy (RT), with 11 patients requiring gastrostomy tube placement during RT. Addition of TORS to overall management of head and neck SCCA spared adjuvant RT or combined chemotherapy and RT (CRT) in 50% of stage I/II tumors and spared chemotherapy in 34% of stage III/IV tumors., Conclusion: TORS is a safe procedure with minimal complications and favorable clinical and functional outcomes. It is a promising future alternative surgical treatment for laryngopharyngeal tumors.

Objectives: to present and discuss a high-performance negative depletion method for the isolation of circulating tumor cells (CTCs) in the blood of patients with head and neck cancer and to determine the correlation between the presence of CTCs and early clinical outcome in these patients., Design: prospective clinical follow-up study of patients with squamous cell carcinoma of the head and neck (SCCHN) undergoing surgical intervention, who had peripheral blood examined for the presence of CTCs., Patients: the study population comprised 48 patients diagnosed as having SCCHN and undergoing surgical intervention., Intervention: a negative depletion process to isolate and quantify CTCs from the blood of patients with SCCHN using immunomagnetic separation was developed and validated. Immunostaining for cytokeratin was performed on the enriched samples to determine the number of CTCs extracted from each patient's blood sample. Correlation of the presence of CTCs, tumor stage, nodal status, clinical characteristics, and outcome was made., Main Outcome Measure: disease-free survival., Results: our initial data, that have a mean follow-up of 19.0 months, suggest that patients with no detectable CTCs per milliliter of blood had a significantly higher probability of disease-free survival (P = .01). There was no correlation between the presence of CTCs with regard to age, sex, tumor site, stage, or nodal involvement., Conclusions: our enrichment technology, based on the removal of normal cells, has been used on the peripheral blood of patients with head and neck cancer for which follow-up data were collected. If no CTCs were present, a statistically significant improved disease-free survival was observed in SCCHN. A blood test with such a prognostic capability could have important implications in the treatment of patients with head and neck cancer.

Objective: To analyze the long-term results and the complications related to an expanded series of maxillary removal and reinsertion (MRRI) with 18-year surgical experience., Study Design: Case series with chart review of the MRRI patients in the last 18 years., Setting: The Ohio State University Comprehensive Cancer Center, James Cancer Hospital and Solove Research Institute., Subjects and Methods: Seventy-eight patients who underwent MRRI from February 1990 through February 2007. The median age was 51 years (range 11-77 yrs). Sixty-two (80%) patients had malignant lesions., Results: MRRI has been successfully completed in all 78 patients, with no intraoperative mortality. The most commonly encountered malignant neoplasm was squamous cell cancer (40.3%), followed by esthesioneuroblastoma (24.1%), adenoid cystic cancer (8%), and other neoplasms (27.4%). The most commonly encountered postoperative complication was diplopia, which has persisted in five (6.4%) patients in the short-term and in three (4%) patients in the long-term follow-up. Nasal asymmetry was the most common long-term complication (17.9%), followed by plate-associated problems (10.2%) and midface asymmetry (10.2%). Overall five-year survival for the patients with squamous cell carcinoma was 62 percent., Conclusion: MRRI is a favorable surgical technique for the treatment of anterior cranial base (ACB) tumors in adults and even in children. It improves operative morbidity by preserving both function and form of the maxillary region and gives excellent exposure to ACB., (Copyright 2010 American Academy of Otolaryngology-Head and Neck Surgery Foundation. Published by Mosby, Inc. All rights reserved.)

Objectives/hypothesis: Assess impact of clinical variables upon survival in patients diagnosed with recurrent head and neck carcinoma and better delineate role of post-treatment surveillance., Methods: Variables including previous tumor site, stage, prior therapy, location of recurrence, patient-identified symptoms, compliance with recommended surveillance, definitive salvage therapy, and clinical outcome were recorded for patients diagnosed with recurrent head and neck cancer from which estimates of survival were generated and compared., Results: One hundred five patients were identified as having been diagnosed with recurrent disease. The majority (81%) were deemed compliant with recommended surveillance. Eighty-nine patients (85%) identified new symptoms/findings prior to diagnosis. Survival was not significantly different between compliant and noncompliant patients (P = .20). For patients who underwent salvage therapy, no significant differences in survival were seen according to original primary site or mode of treatment for recurrence. Better survival was seen in patients with original prior early stage disease (P = .0001) and in patients with local-only site of disease recurrence (P = .0001)., Conclusions: In patients with recurrent disease, survival may relate more to variables associated with prior disease or recurrence location than those associated with follow-up surveillance. Surveillance and salvage therapy for recurrent disease may, however, preferentially benefit certain subgroups: 1) patients with prior early stage disease, and 2) those in whom site of recurrence is local-only. Despite high compliance with recommended surveillance, survival remains extremely poor for patients with recurrent disease previously treated for advanced stage disease or with those with regional recurrence. As such, the impact of routine surveillance upon survival in these patients remains unclear.

Objective: To determine the feasibility of, compliance with, and long-term survival with intensification treatment regimens for patients with advanced, resectable, previously untreated head and neck squamous cell carcinoma., Design: Prospective phase 2 clinical trial (3 similar, consecutively evolved trials)., Setting: Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University., Patients: One hundred twenty-three patients (median age, 60 years; range, 30-78 years) with previously untreated, resectable, advanced squamous cell carcinomas of the oral cavity, oropharynx, or hypopharynx., Interventions: Perioperative cisplatin chemoradiotherapy, surgical resection with intraoperative radiotherapy, and postoperative paclitaxel and cisplatin chemoradiotherapy., Main Outcome Measures: The feasibility, compliance, and long-term survival associated with the 3 intensification regimens., Results: Compliance with all 3 intensification regimens averaged 61% (75/123). Patient-directed noncompliance occurred in 16 patients (13%). The average locoregional (112/123, 91%) and systemic (106/123, 86%) disease control rates were excellent. Overall long-term disease-specific survival was 73%. Median time at risk was 62.5 months (range, 1 day to 100.4 months)., Conclusions: The intensification regimens result in excellent disease control rates and long-term survival in this particular patient population. Future evolution of these regimens will include some modifications to further decrease toxic effects followed by phase 2 multi-institutional trials to determine whether the single-institutional experience can be duplicated. The results of these studies will determine whether phase 3 trials can be proposed.

Background: Long-term disease control of an intensified treatment regimen for previously untreated stage III and IV resectable oral cavity, oropharyngeal, or hypopharyngeal squamous cell carcinoma was analyzed., Methods: Forty-three patients with previously untreated, advanced stage, resectable squamous carcinomas of the oral cavity, oropharynx, or hypopharynx were enrolled in a prospective phase II institutional clinical trial at a tertiary care National Cancer Institute-designated comprehensive cancer center. It includes preoperative accelerated hyperfractionated radiotherapy with concurrent cisplatin followed immediately by surgery and intraoperative radiotherapy, and completed with early postoperative weekly paclitaxel, two additional cisplatin cycles, and concurrent once-daily radiotherapy beginning on day 28 after surgery., Results: Forty-three patients enrolled in the study. Protocol compliance was 53%. The range of time at risk was 10.4 to 56.23 months (median, 45 months). The locoregional (93%) and systemic (91%) disease control rates were excellent. Overall long-term survival was 79%., Conclusions: An intensive treatment regimen that improves compliance and long-term disease control is clearly feasible for this patient population.

Objective: To assess the significance of cyclo-oxygenase 2 (COX-2) in laryngeal squamous cell carcinoma (LSCC)., Study Design: An immunohistochemical study in which 39 patients with LSCC were included., Methods: Immunohistochemical staining of the paraffin-embedded tumour tissues was performed using isoform-specific COX-2 polyclonal antisera (Santa Cruz, Calif., USA). COX-2 results were compared with the clinical parameters of the patients., Results: COX-2 was detected in all tumour tissues. In the normal laryngeal tissue around the tumour area, which served as control, there was no COX-2 staining. There was no relationship between the COX-2 results and the location of the primary tumour, T stage and N stage, survival, recurrence or pulmonary metastases., Conclusion: The absence of a relation between COX-2 positivity and clinical parameters may suggest an involvement of COX-2 in laryngeal carcinogenesis. Since COX-2 positivity could be detected in all LSCC specimens studied, COX-2 could serve as a therapeutic target in LSCC., (Copyright 2004 S. Karger AG, Basel)

The major cells involved in cancer cell kill are the T lymphocytes. However, T cells need to be activated upon antigen presentation, which is mediated by the antigen presenting cells, one of which is the Langerhans cell (LC). The purpose of this study was to assess the significance of LC and inflammatory cell infiltration in the laryngeal squamous cell carcinoma (LSCC). Forty-five patients who were operated on for LSCC between 1992 and 1999 were included in the study. The clinical and histopathological features of the patients were reviewed. A semiquantitative estimation of the lymphocyte dominant inflammatory reaction within and around the tumor was performed. Anti S-100 antibodies were used for immunohistochemical detection of LCs. Horseradish peroxidase method was used. LCs were present in almost all of the specimens within and around the tumor tissue. The S-100 results did not associate with grade, T and N stages, tumor stage, laryngeal site of involvement and survival (P>0.05). The S-100 results significantly associated with inflammatory reaction in the tumor tissue (P<0.01). In conclusion, the LC related response is not important to inhibit regional metastasis by cancer cells. The LC is not a reliable tool to determine prognosis of the patients with LSCC in the clinical practice.

Purpose: To determine whether changes in the Ki-67 index during the early course of radiotherapy could predict the prognosis in squamous cell carcinoma of the uterine cervix and be of value in clinical practice., Materials and Methods: Biopsy specimens from 23 cases of histologically confirmed squamous cell carcinoma of the cervix were stained with anti-Ki-67 monoclonal antibody prior to radiotherapy and after 9 Gy. The correlation between the Ki-67 index, local control and distant metastasis was determined by Spearman's correlation test., Results: Median age of the patients was 49. According to the FIGO staging system four patients had Stage IIA, 16 had Stage IIB, one had Stage IIIA and two had Stage IIIB disease. Among the whole group brachytherapy was applied to 17 patients (17/23) and weekly cisplatin (40 mg/m2) was applied to 15 patients (15/23). The mean Ki-67 index prior to radiotherapy and after 9 Gy for the entire group were 58.5% and 46.0%, respectively. The Ki-67 index after 9 Gy decreased in most of the patients (74%). During a median follow-up of 23 months four patients developed local recurrence and four patients developed distant metastasis. No significant correlation was detected among the local control and changes in Ki-67 index after 9 Gy, whereas there was a moderate correlation between distant metastasis and changes in Ki-67 index after 9 Gy (r = 0.51, p = 0.01)., Conclusion: The Ki-67 index can be used safely as a proliferation marker in cervical carcinomas, and changes in the Ki-67 index during the early course of radiotherapy may predict the metastatic potential. However prospective studies including a large number of patients with long-term follow-up are necessary to confirm the clinical utility of this marker in cervical cancer.

Objectives: To elucidate the clinical and histopathological significance of the proliferative activity as determined by PCNA and Ki67 levels and mitotic counting (MC) in laryngeal squamous cell cancer (LSCC)., Study Design: An analysis of clinical, histopathological and immunhistochemical (PCNA0 and Ki67) results of 28 patients, who were treated for LSCC, was made., Methods: Clinical data of the patients were reviewed and corresponding archival paraffin embedded tissue samples were obtained. Histopathological studies and MC were performed, and PCNA and Ki67 positivity was assessed., Results: There was no association between the mean values of the proliferative markers, and N stage and T stage of the patients as well as laryngeal site of involvement (p > 0.05). There was a correlation between the proliferative indicators and tumor grade (p < 0.05). A correlation was also encountered between the PCNA, Ki67 and MC values (p = 0.02)., Conclusion: The proliferative markers studied are not reliable indicators for the presumptive diagnosis of occult neck metastasis. They may be used as complementary tools to the conventional histopathologic grading systems to assess the tumour differentiation in LSCC.

Keratoacanthomas and squamous cell carcinomas of the skin share many histopathologic features, making differential diagnosis difficult. The aim of this study is to investigate the staining pattern of proliferating cells in keratoacanthomas and squamous cell carcinomas of the skin and to evaluate the value of nuclear morphometric criteria in differential diagnosis. Mean nuclear volume was assessed in 21 keratoacanthomas and 21 squamous cell carcinomas in tissue sections by a stereologic method. Immunohistochemical expression of Ki-67 monoclonal antibody was assessed and the distribution pattern (random or peripheral) of proliferating cells evaluated. Mean nuclear volume (MNV +/- SD) was 590 +/- 293.0 for squamous cell carcinomas and 615 + 305.9 for keratoacanthomas. Statistical analysis showed no significant differences between both groups (p = 0.78) in terms of mean nuclear volume values. Proliferating cells in keratoacanthomas showed a peripheral distribution, whereas there was a random distribution of proliferating cells in squamous cell carcinomas. Our results indicate that quantitative nuclear features are not helpful in making a differentiation between keratoacanthomas and squamous cell carcinomas, while immunohistochemistry with Ki-67 antibody may give useful additional information in differential diagnosis.