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Cancer neurobiology is an emerging discipline that inevitably unfurls new perspectives in oncology. The role that nerves play in cancer progression resonates with the long-reported dependency of tumors on neuro-molecular mechanisms that remain insufficiently elucidated. Whereas interactions between neurotrophic growth factors and receptors have been heavily studied in the nervous system, their expression in cancers and their impact on tumor cell growth and metastasis through their corresponding signaling pathways has been undervalued. Accumulating evidence suggests that trophic factors released by nerves strongly influence tumor development and that this neural contribution appears to not only play a stimulatory role but also function as an essential part of the tumor’s microenvironment. This bidirectional communication between proliferating cells and tumor-infiltrating nerves drives axonogenesis and tumor growth and migration. Acquiring a better understanding of the trophic interactions between primary afferent neurons and invading tumors will guide clinically actionable strategies to prevent tumor-associated axonogenesis, disrupting the chemical crosstalk between neurons and tumors and ultimately decreasing tumor growth and spread.

Peptide fibril nanostructures have been advocated as components of future biotechnology and nanotechnology devices. However, the ability to exploit the fibril functionality for applications, such as catalysis or electron transfer, depends on the formation of well-defined architectures. Fibrils made of peptides substituted with aromatic groups are described presenting efficient electron delocalization. Peptide self-assembly under various conditions produced polymorphic fibril products presenting distinctly different conductivities. This process is driven by a collective set of hydrogen bonding, electrostatic, and π-stacking interactions, and as a result it can be directed towards formation of a distinct polymorph by using the medium to enhance specific interactions rather than the others. This method facilitates the detailed characterization of different polymorphs, and allows specific conditions to be established that lead to the polymorph with the highest conductivity.

The local extension of cancer cells along nerves is a frequent clinical finding for various tumours. Traditionally, nerve invasion was assumed to occur via the path of least resistance; however, recent animal models and human studies have revealed that cancer cells have an innate ability to actively migrate along axons in a mechanism called neural tracking. The tendency of cancer cells to track along nerves is supported by various cell types in the perineural niche that secrete multiple growth factors and chemokines. We propose that the perineural niche should be considered part of the tumour microenvironment, describe the molecular cues that facilitate neural tracking and suggest methods for its inhibition.

Background A positive margin is among the most significant factors that affects the outcome in head and neck squamous cell carcinoma (SCC). The purpose of this study was to compare the negative margin rates between 2 methods of intraoperative margin assessment in patients with oral cavity SCC. Methods A prospective, randomized controlled trial comparing 2 methods of intraoperative margin assessment: specimen-driven margins and patient-driven margins. Results The final analysis included 71 patients, 20 (29%) in the patient-driven margin arm. Frozen section analysis revealed positive/close surgical margins that led to an extension of the surgical resection in 22 of 51 patients (43%) in the specimen-driven margin arm, and 2 of 20 patients (10%) in the patient-driven margin arm (p = .01). After final pathological analysis, the wide negative margin rate was 84% in the specimen-driven margin arm, compared to 55% in the patient-driven margin arm (p = .02). Extension of the surgical resection prevented escalation of adjuvant treatment in 19 patients (38%) in the specimen-driven margin arm and 10% in the patient-driven margin arm. Conclusion Specimen derived margin assessment led to significant improvement in the rate of negative margins. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1803–E1809, 2016

One of the limitations of cancer research has been the restricted focus on tumor cells and the omission of other non-malignant cells that are constitutive elements of this systemic disease. Current research is focused on the bidirectional communication between tumor cells and other components of the tumor microenvironment (TME), such as immune and endothelial cells, and nerves. A major success of this bidirectional approach has been the development of immunotherapy. Recently, a more complex landscape involving a multi-lateral communication between the non-malignant components of the TME started to emerge. A prime example is the interplay between immune and endothelial cells, which led to the approval of anti-vascular endothelial growth factor-therapy combined with immune checkpoint inhibitors and classical chemotherapy in non-small cell lung cancer. Hence, a paradigm shift approach is to characterize the crosstalk between different non-malignant components of the TME and understand their role in tumorigenesis. In this perspective, we discuss the interplay between nerves and immune cells within the TME. In particular, we focus on exosomes and microRNAs as a systemic, rapid and dynamic communication channel between tumor cells, nerves and immune cells contributing to cancer progression. Finally, we discuss how combinatorial therapies blocking this tumorigenic cross-talk could lead to improved outcomes for cancer patients.

Spasticity is a pathological condition that can occur in people with neuromuscular disorders. Objective, repeatable metrics are needed for evaluation to provide appropriate treatment and to monitor patient condition. Herein, an instrumented bimodal glove with force and movement sensors for spasticity assessment is presented. To mitigate noise artifacts, machine learning techniques are used, specifically a multitask neural network, to calibrate the instrumented glove signals against the ground truth from sensors integrated in a robotic arm. The motorized robotic arm system offers adjustable resistance to simulate different levels of muscle stiffness in spasticity, and the sensors on the robot provide ground‐truth measurements of angular displacement and force applied during flexion and extension maneuvers. The robotic sensor measurements are used to train the instrumented glove data through multitask learning. After processing through the neural network, the Pearson correlation coefficients between the processed signals and the ground truth are above 0.92, demonstrating successful signal calibration and noise mitigation.

Background: Sinonasal undifferentiated carcinoma (SNUC) is a rare, highly aggressive cancer that arises in the nasal cavity and paranasal sinuses. Despite aggressive multimodal therapy the prognosis remains poor. Because of the locally advanced nature of SNUC, we have used cisplatin-based induction chemotherapy before definitive surgery or radiation therapy in our institution. Unfortunately, about 30% of SNUC patients do not respond to this treatment, and the lack of response is associated with poor survival. Therefore, developing strategies to overcome resistance to induction chemotherapy is crucial. Our current gene expression analysis of SNUC specimens indicated that the TGFβ signaling pathway might be activated in nonresponders. Using the MDA8788-6 SNUC cell line established from a nonresponder, we found that TGFβ signaling is upregulated in an autocrine manner in the SNUC cell line. Since inhibition of the TGFβ pathway overcame cisplatin resistance in this cell line, we decided to examine the effects of TGFβ inhibition in vivo. Materials and Methods: The MDA8788-6 SNUC cell line were cultured under serum-free condition overnight to induce TGFβ signaling. The cells were then resuspended in the serum-free conditioned medium collected from the same cell line to maintain activation of the pathway. Two million MDA8788-6 cells in the conditioned medium were inoculated into the flank of mice subcutaneously. On the same day of the inoculation, we started treatment with i) vehicle control, ii) cisplatin only (4 mg/kg, once per week, intravenously), iii) EW-7197 only (TGFβRI specific inhibitor, 40 mg/kg, five times per week, oral gavage), and iv) cisplatin plus EW-7197. After 5 courses of treatments, the mice were sacrificed. Average tumor volume of each treatment group 31 days after the cell inoculation was compared by Tukey’s multiple comparisons test. Area under the curve (AUC) was calculated according to the tumor growth curve of each mouse from 0 to 31 days after the cell inoculation. AUC of CDDP group and CDDP plus EW-7197 group was compared by unpaired, two-tailed t test with Welch’s correction. Results: The EW-7197 treated group itself did not show antitumor growth effect compared to the control group. Comparison of AUC of the tumor volume showed significant difference between the cisplatin alone and cisplatin plus EW-7197; the combination of cisplatin and EW-7197 had better antitumor growth effect compared to cisplatin alone. Conclusions: Our finding suggests that TGFβ inhibition may offer hope to SNUC patients struggling with chemoresistance. Citation Format: Yoko Takahashi, Hideaki Takahashi, Moran Amit, Frederico O. Gleber-Netto, Diana Bell, Tong-Xin Xie, Dianna Roberts, Ahmed S. Abdelmeguid, Curtis Pickering, Jeffrey N. Myers, Ehab Y. Hanna. Overcoming cisplatin resistance in sinonasal undifferentiated carcinoma by inhibiting the TGFβ signaling pathway in vivo [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr B08.

Purpose To explore treatment-related changes in symptom burden and quality of life (QOL) in oropharyngeal squamous cell cancer (OPSCC) patients treated surgically and non-surgically. Patients and Methods Eighty-six patients with human papillomavirus–associated OPSCC treated at the Head and Neck Center at The University of Texas MD Anderson Cancer Center were recruited to a prospective registry study between 2014 and 2016 and completed the core, head and neck-specific, and symptom interference sections of the MD Anderson symptom inventory (MDASI) multi-symptom questionnaire and the EQ-5D health status assessment as a measure of QOL at four time points. Results Longitudinal improvements from post-treatment nadir were observed across all groups. For patients treated with single modality, symptom interference, but not core and head and neck specific, MDASI scores were significantly better at 6 months in patients treated with surgery than radiation (P = 0.04). For patients treated with multiple modalities, scores for each of the three domains (i.e., core, head and neck -specific, and interference MDASI) were significantly better in the surgical group than the nonsurgical group at treatment completion (P = 0.0003, P = 0.0006 and P = 0.02) and 6 weeks (P = 0.001, P = 0.05 and P = 0.04), but not 6 months (P = 0.11, P = 0.16 and P = 0.040). No significant differences in EQ5D health status were observed between groups at any time point, reflecting similar overall QOL in all groups. Conclusion Symptom burden and QOL improves after treatment in OPSCC survivors over time regardless of whether primary surgical or nonsurgical treatment is used, although acute symptom profiles may differ.

Background Depth of invasion (DOI) in oral cavity cancer is important in determining prognosis. This study aims to determine optimal cut-points of DOI for detection of occult disease and survival. Methods A retrospective cohort study was completed of previously untreated early stage lateral oral tongue cancer. DOI cut-points were computed. Multiple logistic regression and multivariate Cox proportional hazards models were used to assess predictors of occult nodal disease and overall survival (OS) and disease-specific survival (DSS). Results Occult nodal disease was found in 55 (26%) of the 212 patients. DOI of 7.25 mm was most predictive for occult nodal disease and 8 mm for OS and DSS. DOI was an independent predictor of OS and DSS. Conclusion The optimal DOI cut-point for detection of occult nodal metastasis was 7.25 and 8 mm for OS and DSS at 5 years. DOI is an independent predictor of OS and DSS.

Sinonasal mucosal melanoma (SNMM) is a rare oncological entity that comprises most head and neck mucosal melanomas. SNMM has distinctive genetic background, different from cutaneous melanoma. Survival outcomes among SNMM patients are poor; while there is no clear consensus on the optimal management of SNMM, the primary treatment modality is generally considered to be wide surgical excision, and radiation therapy (RT) is often used in the postoperative adjuvant setting to improve locoregional control. Systemic therapies have demonstrated little or no survival benefit, and most SNMM patients die of distant metastatic disease. Owing to the rarity of the disease, the literature describing treatment approaches for SNMM is lacking and largely limited to isolated case reports and retrospective series. Here, we describe contemporary diagnostic and therapeutic approaches to SNMM based on the most recent molecular and outcome data.

Pancreas cancer cells have a tendency to invade along nerves. Such cancerous nerve invasion (CNI) is associated with poor outcome; however, the exact mechanism that drives cancer cells to disseminate along nerves is unknown. Immunohistochemical analysis of human pancreatic ductal adenocarcinoma (PDAC) specimens showed overexpression of the L1 cell adhesion molecule (L1CAM) in cancer cells and in adjacent Schwann cells (SC) in invaded nerves. By modeling the neural microenvironment, we found that L1CAM secreted from SCs acts as a strong chemoattractant to cancer cells, through activation of MAP kinase signaling. L1CAM also upregulated expression of metalloproteinase-2 (MMP-2) and MMP-9 by PDAC cells, through STAT3 activation. Using a transgenic Pdx-1-Cre/KrasG12D /p53R172H (KPC) mouse model, we show that treatment with anti-L1CAM Ab significantly reduces CNI in vivo. We provide evidence of a paracrine response between SCs and cancer cells in the neural niche, which promotes cancer invasion via L1CAM secretion.

Noncovalent interactions are the main driving force in the folding of proteins into a 3D functional structure. Motivated by the wish to reveal the mechanisms of the associated self-assembly processes, scientists are focusing on studying self-assembly processes of short protein segments (peptides). While this research has led to major advances in the understanding of biological and pathological process, only in recent years has the applicative potential of the resulting self-assembled peptide assemblies started to be explored. Here, major advances in the development of biomimetic supramolecular peptide assemblies as coatings, gels, and as electroactive materials, are highlighted. The guiding lines for the design of helical peptides, β strand peptides, as well as surface binding monolayer-forming peptides that can be utilized for a specific function are highlighted. Examples of their applications in diverse immerging applications in, e.g., ecology, biomedicine, and electronics, are described. Taking into account that, in addition to extraordinary design flexibility, these materials are naturally biocompatible and ecologically friendly, and their production is cost effective, the emergence of devices incorporating these biomimetic materials in the market is envisioned in the near future.

Charge transfer at the interface between the active layer and the contact is essential in any device. Transfer of electronic charges across the contact/active layer interface with metal contacts is well-understood. To this end, noble metals, such as gold or platinum, are widely used. With these contacts, ionic currents (especially protonic) are often neglected because ions and protons do not transfer across the interface between the contact and the active layer. Palladium hydride contacts have emerged as good contacts to measure proton currents because of a reversible redox reaction at the interface and subsequent absorption/desorption of H into palladium, translating the proton flow reaching the interface into an electron flow at the outer circuit. Here, we demonstrate that gold and palladium contacts also collect proton currents, especially under high relative humidity conditions because of electrochemical reactions at the interface. A marked kinetic isotope effect, which is a signature of proton currents, is observed with gold and palladium contacts, indicating both bulk and contact processes involving proton transfer. These phenomena are attributed to electrochemical processes involving water splitting at the interface. In addition to promoting charge transfer at the interface, these interfacial electrochemical processes inject charge carriers into the active layer and hence can also modulate the bulk resistivity of the materials, as was found for the studied peptide fibril films. We conclude that proton currents may not be neglected a priori when performing electronic measurements on biological and bioinspired materials with gold and palladium contacts under high humidity conditions.

Background The role of human papillomavirus (HPV) infection in oropharyngeal cancer (SCC) is well established. The annual incidence of oropharyngeal SCC in Israel is considerably lower than that in the United States. The purpose of this study was to assess the rate of HPV-related oropharyngeal SCC in Israel. Methods The cohort included patients with oropharyngeal SCC who were treated during 1999 to 2011 in Israel. HPV typing was carried out using reverse hybridization and immunohistochemistry. Results Of the 74 patients analyzed, 25 (33.7%) had detectable HPV DNA. Patients in the HPV-positive group tended to be younger, with a higher rate of nodal metastases, and no history of smoking (p

Background We hypothesized that pathological N1 (pN1) and N2a (pN2a) nodal disease portend a similar prognosis in patients with oral cancer. Methods An international multicenter study of 739 oral squamous cell carcinoma (SCC) patients with pN1 or pN2a stage disease was conducted. Multivariable analyses were performed using Cox proportional hazard models to compare locoregional failure, disease-specific survival (DSS), and overall survival (OS). Institutional heterogeneity was assessed using 2-stage random effects meta-analysis techniques. Results Univariate analysis revealed no difference in locoregional failure (p = .184), DSS (p = .761), or OS (p = .475). Similar results were obtained in adjusted multivariable models and no evidence of institutional heterogeneity was demonstrated. Conclusion The prognosis of pN2a and pN1 disease is similar in oral SCC suggesting these categories could be combined in future revisions of the nodal staging system to enhance prognostic accuracy. However, these results may reflect more aggressive treatment of N2a disease; hence, we caution against using these data to deintensify treatment. © 2014 Wiley Periodicals, Inc. Head Neck, 2015

Objectives Elective neck dissection during salvage laryngectomy is controversial. The goal of our study was to evaluate the effect of elective neck dissection during salvage laryngectomy in patients with locally advanced disease at recurrence. Design Multicentre, retrospective study. Settings Two tertiary medical centres. Participants Eighty-seven patients treated by salvage laryngectomy. Main outcome measures Disease-Free and Overall Survival. Results Fifty-seven patients underwent salvage total laryngectomy for locally advanced recurrent squamous cell carcinoma of the larynx, and 30 patients underwent salvage laryngectomy for limited recurrent disease. Elective lateral neck dissection was performed in 48 patients. The groups were similar in age, sex, initial TNM stage and pre-operative treatment. Survival analysis showed that both disease-free survival and overall survival were improved in patients with locally advanced disease who underwent elective neck dissection. This beneficial effect was not demonstrated in patients with limited disease at recurrence. Multivariate analysis showed that the extent of the recurrent disease as well as elective neck dissection was associated with improved disease-free survival and overall survival. Conclusions Elective neck dissection during salvage total laryngectomy seems to improve survival in patients with advanced local disease at recurrence. The role of neck dissection in the treatment of smaller tumours awaits further studies.

It was suggested that the brain microenvironment plays a role in glioma progression. Here we investigate the mechanism by which astrocytes which are abundant in glioma tumors, promote cancer cell invasion. In this study, we evaluated the effects of astrocytes on glioma biology both in vitro and in vivo and determined the downstream paracrine effect of glial-derived neurotrophic factor (GDNF) on tumor invasion. Astrocytes-conditioned media (ACM) significantly increased human and murine glioma cells migration compared to controls. This effect was inhibited when the activity of GDNF on glioma cells was blocked by RET-Fc chimera or anti-GDNF Ab and by small interfering RNA directed against GDNF expression by astrocytes. Glioma cells incubated with ACM led to time dependent phosphorylation of the GDNF receptor, RET and downstream activation of AKT. Tumor migration and GDNF-RET-AKT activation was inhibited by the RET small-molecule inhibitor pyrazolopyrimidine-1 (PP1) and by the AKT inhibitor LY294002. Finally, blocking of RET by PP1 or knockout of the RET coreceptor GFRα1 in glioma cells reduced the size of brain tumors in immunocompetent mice. We suggest a mechanism by which astrocytes attracted to the glioma tumors facilitate brain invasion by secretion of GDNF and activation of RET/GFRα1 receptors expressed by the cancer cells.

Importance As incidence of differentiated thyroid cancer rises, treatment paradigms have become increasingly defined. Despite this, locally advanced disease continues to be challenging to manage. Postoperative therapy in the form of radioactive iodine (RAI) is generally recommended, but the role of external beam radiation therapy (EBRT) is less well defined. Objective To investigate the role of EBRT in locally advanced differentiated thyroid cancer. Design, Setting, and Participants For this retrospective cohort study, patients treated surgically for T4a differentiated thyroid cancer at the University of Texas MD Anderson Cancer Center from January 2000 through December 2015 were recruited, and 88 patients were included for analysis. Exposures Adjuvant treatment with RAI alone or both RAI and EBRT. Main Outcomes and Measures Disease-free survival (DFS), defined as the time from primary surgery to locoregional or distant recurrence or death due to any cause. Kaplan-Meier survival analysis was completed. Univariate and multivariate analysis was completed with Cox proportional hazards model to determine predictors of DFS. Results A total of 88 patients (44 women [50%]; mean [SD] age, 58.2 [15.3] years) were included in the analysis. Median (range) follow-up was 117 (12-164) months. Forty-four patients (50%) underwent RAI alone and 44 patients (50%) underwent RAI with adjuvant EBRT. Patients undergoing RAI alone did not receive EBRT owing to invasion into the recurrent laryngeal nerve only (n = 14 [32%]) or invasion into the tracheal perichondrium and/or esophageal muscularis only (n = 18 [41%]). Five-year DFS was 43% in those undergoing RAI alone, compared with 57% in those undergoing RAI and EBRT (effect size = 14%; 95% CI, −7% to 33%). Patients undergoing RAI alone had an increased rate of locoregional failure (effect size = −32%; 95% CI, −47% to −16%), with those undergoing RAI treatment alone, for minimal tracheal perichondrium and/or esophageal muscularis invasion having worse locoregional control than those with recurrent laryngeal nerve invasion only (effect size = 49%; 95% CI, 20% to 71%). Age (adjusted hazard ratio [adjusted HR], 1.02/y; 95% CI, 1.00 to 1.05) and esophageal invasion (adjusted HR, 2.30; 95% CI, 1.16 to 4.60) were independent predictors of worse DFS. Conclusions and Relevance The addition of EBRT to RAI results in good disease control in locally advanced differentiated thyroid cancer, particularly in patients with tracheal or esophageal invasion treated with aggressive surgical resection. Increased age and presence of esophageal invasion were independent predictors of poor disease control.

We aimed to better define the most appropriate therapeutic protocol for this type of tumor.The incidence of well-differentiated thyroid carcinoma is rising and the mortality from the disease remains low for patients with early disease. Nevertheless, the survival of patients with advanced disease has not improved during the last four decades and a controversy still exists in the literature regarding the optimal treatment in patients with locally advanced (T4) differentiated thyroid carcinoma.Meta-analysis of the literature and our institutional experience, in treating patients with advanced papillary/follicular thyroid carcinoma. The main outcome measures were overall survival (OS) and disease-specific survival (DSS).The study group consisted of 38 patients with locally advanced thyroid carcinoma (T4). Regional spread to nodal metastases was present in 25 (65.7%) patients. Tracheal invasion was diagnosed in 29 (76.3%), of those 10 (26.3%) patients had airway obstruction. Recurrent laryngeal nerve (RLN) paralysis was revealed with clinical evidence during diagnosis in 23 (60.5%) patients. The 5-years OS was 66% and DSS was 87%. Multivariate analysis of outcome showed that undifferentiated carcinoma foci and vocal cord paralysis were associated with significantly reduced 5-years OS, and vocal cord paralysis was the only independent prognostic variable for DSS. Male gender and adjuvant radioactive iodine treatment were significant prognostic variables for disease free survival but not OS or DSS.Surgical resection remains the mainstay of treatment for locally advanced differentiated thyroid cancers. Foci of poorly differentiated cells, vocal cord paralysis and male gender are associated with poor prognosis. Radioactive iodine treatment improved local control but did not not affect OS. These patients should be managed by a multidisciplinary team in university centers specializing in treating complicated cancer patients.

Low-cost infrared photo-transistors with improved detectivity (i.e. higher signal-to-noise ratio) could find further use in spectral analysis, which is important for chemical identifications, as well as other applications from environmental monitoring to optical communications. Accordingly, the main goal of this research is to advance printed, flexible photo-transistors by using a family of novel donor-acceptor polymers with narrow bandgap that are responsive in the short wavelength infrared (SWIR) region. In particular, the transistors show optical response extending out to a wavelength of 1.8 micrometer. The external quantum efficiency and the rectification ratio are used to characterize the performance of devices with different polymer layer thickness, in order to optimize detectivity. The individual transistors could further be exploited for the fabrication of integrated arrays for bio-medical and/ or robotic applications. It paves the way to large-area, conformal designs that are currently not achievable with conventional inorganic SWIR materials.

The evolution of surgical oncologic technology has moved toward reducing patient morbidity without compromising oncologic resection. In head and neck surgery, organ-preserving techniques have paved the way for the development of transoral approaches that remove tumors of the upper aerodigestive tract without external incisions and potentially spare patients adjuvant treatment. The introduction of robotic-assisted surgery and transoral robotic surgery (TORS) reflects progression of the current transoral techniques to the upper aerodigestive tract. This chapter reviews the evolution of robotic-assisted surgery. We discuss its applications in head and neck surgery and early oncologic and functional outcomes, training of surgeons, costs, and future directions.

Digital pathology diagnostics are often based on subjective qualitative measures. A murine model of early-phase pancreatic ductal adenocarcinoma provides a controlled environment with a priori knowledge of the genetic mutation and stage of the disease. Use of this model enables the application of supervised learning methods to digital pathology. A computerized diagnostics system for histological detection of pancreatic adenocarcinoma was developed and tested. METHODS : Pathological HE-stained specimens with early pancreatic lesions were identified and evaluated with a system that models cancer detection using a top-down object learning paradigm, mimicking the way a pathologist learns. First, the dominant primitives were identified and segmented in the images, i.e., the ducts, nuclei and tumor stroma. A boost-based machine learning technique was used for duct segmentation, classification and outlier pruning. Second, a set of morphological features traditionally used for cancer diagnosis which provides quantitative image features was employed to quantify subtle findings such as duct deformation and nuclei malformations. Finally, a visually interpretable predictive model was trained to distinguish between normal tissue and premalignant cancer lesions, given ground truth samples. RESULTS : A predictive success rate of 92% was achieved using tenfold cross-validation and 93% on an independent test set. Comparison was made with state-of-the-art classification algorithms that are not interpretable as visible features yielded the contribution of individual primitive features to the prediction outcome.Quantitative image analysis and classification were successful in preclinical histology diagnosis for early-stage pancreatic adenocarcinoma. The usage of annotated contours coupled with interpretable supervised learning methods and outlier pruning can be adapted to other medical imaging tasks. The usage of interpretable supervised learning techniques may improve the success of CAD in histopathological diagnosis.

Objective: This study aimed to create a reliable and reproducible orthotopic mouse model of laryngeal malignancy that recapitulates its biologic behavior, local invasiveness, and spread as seen in patients. Methods: Via direct laryngoscopy, human squamous cell carcinoma line FaDu (ATCC HTB-43) was implanted in the larynx (supraglottis and glottis) in nu/nu mice (n = 31). Animals were monitored with direct laryngoscopy and ultrasound for tumor growth and survival. Specimens of larynxes, neck lymphatics, livers, and lungs were removed for histopathologic evaluation to assess tumor extension, thyroid cartilage invasion, and nodal spread. Results: Thirty-one successful direct laryngoscopies were performed. Supraglottic and glottic tumor uptake was 100% and 25%, respectively. Median survival for the animals with supraglottic tumors was 35 days. Histopathologic evaluation revealed pre-epiglottic extension, paraglottic extension, thyroid cartilage invasion, and lymph node metastasis. Conclusion: We describe the first orthotopic model for laryngeal cancer. Our model faithfully recapitulates the phenotype and malignant behavior that reproduces its natural biologic behavior as seen in laryngeal cancer patients. This model offers an opportunity to identify and specifically target therapy for larynx squamous cell carcinoma.

Background The purpose of this study was to characterize the incidence, pattern of spread, and prognostic correlation of nerve invasion in patients with adenoid cystic carcinoma (ACC). Methods Using 3 different pathological categories of perineural invasion, intraneural invasion, and perineural inflammation, we investigated the prognostic value of nerve invasion in a total of 495 ACCs from 9 international patient cohorts with median follow-up 90 months (range, 12–288 months). Results Of 239 patients (48%) with nerve invasion, 174 (73%) had perineural invasion, 65 (27%) intraneural invasion, and 37 (15%) perineural inflammation. Multivariate Cox regression analysis identified tumor site (p = .008; hazard ratio [HR] = 1.8; 95% confidence interval [CI] = 0.07–3.7) and intraneural invasion (p < .001; HR = 5.9; 95% CI = 0.8–12.3) as independent prognostic markers for both overall survival (OS) and disease-specific survival (DSS), but not of distant metastases. Conclusion Although perineural invasion has no impact on survival, intraneural invasion is an independent predictor of poor prognosis. Recognition of intraneural invasion may help optimize treatment of patients with head and neck ACC. © 2014 Wiley Periodicals, Inc. Head Neck 37: 1038–1045, 2015

Background The patterns of regional metastasis in adenoid cystic carcinoma (ACC) of the head and neck and its association with outcome is not established. Methods We conducted a retrospective multicentered multivariate analysis of 270 patients who underwent neck dissection. Results The incidence rate of neck metastases was 29%. The rate observed in the oral cavity is 37%, and in the major salivary glands is 19% (p = .001). The rate of occult nodal metastases was 17%. Overall 5-year survival rates were 44% in patients undergoing therapeutic neck dissections, and 65% and 73% among those undergoing elective neck dissections, with and without nodal metastases, respectively (p = .017). Multivariate analysis revealed that the primary site, nodal classification, and margin status were independent predictors of survival. Conclusion Our findings support the consideration of elective neck treatment in patients with ACC of the oral cavity. © 2014 Wiley Periodicals, Inc. Head Neck 37: 1032–1037, 2015

Protons and electrons are being exploited in different natural charge transfer processes. Both types of charge carriers could be, therefore, responsible for charge transport in biomimetic self-assembled peptide nanostructures. The relative contribution of each type of charge carrier is studied in the present work for fi brils self-assembled from amyloid- β derived peptide molecules, in which two non-natural thiophene-based amino acids are included. It is shown that under low humidity conditions both electrons and protons contribute to the conduction, with current ratio of 1:2 respectively, while at higher relative humidity proton transport dominates the conductance. This hybrid conduction behavior leads to a bimodal exponential dependence of the conductance on the relative humidity. Furthermore, in both cases the conductance is shown to be affected by the peptide folding state under the entire relative humidity range. This unique hybrid conductivity behavior makes self-assembled peptide nanostructures powerful building blocks for the construction of electric devices that could use either or both types of charge carriers for their function.

Objective Chordoma is a locally aggressive tumor. The aim of this study was to assess the efficacy of different surgical approaches and adjuvant radiation modalities used to treat these patients. Design Meta-analysis. Main Outcome Measures Overall survival (OS), disease-specific survival (DSS), and progression-free survival (PFS). Results The 5-year OS and PFS rates of the whole cohort (n = 467) were 86% and 65.7%, respectively. The 5-year DSS for patients who underwent open surgery and endoscopic surgery was 45% and 49%, respectively (p = 0.8); PFS was 94% and 79%, respectively (p = 0.11). The 5-year OS of patients treated with surgery followed by adjuvant radiotherapy was 90% compared with 70% of those treated by surgery alone (p = 0.24). Patients undergoing partial resection without adjuvant radiotherapy had a 5-year OS of 41% and a DSS of 45%, significantly lower than in the total-resection group (p = 0.0002 and p = 0.01, respectively). The complication rates were similar in the open and endoscopic groups. Conclusions Patients undergoing total resection have the best outcome; adjuvant radiation therapy improves the survival of patients undergoing partial resection. In view of the advantages of minimally invasive techniques, endoscopic surgery appears an appropriate surgical approach for this disease.

Objectives/Hypothesis In the present study we sought to define the outcome of patients with delay in diagnosis and treatment (>1 year) of well-differentiated thyroid carcinoma (WDTC) due to initial benign cytology (IBC). Study Design Retrospective medical record review and analysis of survival outcomes. Methods The records of 47 patients with delayed diagnosis of thyroid cancer were reviewed. In 38, surgery was performed for growing nodules and in nine due to malignant cytology during follow-up. Median time to delayed surgery was 52 months (range, 13–205 months). Multivariate analysis was performed to assess variables associated with outcome. Results Most patients (32/47) underwent total thyroidectomy, whereas 15/47 had hemithyroidectomy. With a median follow-up of 96 months (range, 12–184 months), the 5-year disease-free survival of these patients was 96%. Multivariate analysis showed that the outcome of these patients was not statistically different than that of patients (n = 162) who underwent immediate surgery for similar disease. Conclusions We show that patients with delayed diagnosis and treatment for WDTC due to IBC have excellent outcome. Level of Evidence 4 Laryngoscope, 124:2837–2840, 2014

The minimal clinically important difference (MCID) is defined as the smallest difference in quality of life (QOL) that patients perceive as beneficial and that mandates a change in management. We aimed to determine the MCID among patients with oral cavity and oropharyngeal cancer and to identify domains that are significantly affected during treatment. The cohort consisted of 1,011 patients analyzed by a metaanalysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. MCID values for the University of Washington Quality of Life Questionnaire (UW-QOLQ) and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC C-30) and Head and Neck-35 questionnaires were calculated by using the distribution-based method. The mean MCID for Global QOL was 13.07 points for the UW-QOLQ and 9.43 in the EORTC C-30 questionnaire. High consistency in the MCID values was found between the two questionnaires examined. Heat map analysis indicated a clinically significant improvement in head and neck-associated domains and in domains associated with general cancer treatment 1 year or more after treatment relative to 3 months after treatment (p

The incorporation of non-canonical amino acids with aromatic side chains is considered to be a promising way to improve and control the electronic properties of self-assembled peptide nanostructures. In this work, we have studied the influence of aromatic ring heteroatom on the electronic properties of amyloid β-derived peptide fiber networks. We show that the incorporation of furan instead of thiophene side chains results in only small changes in the resistivity of the peptide network, with a threefold increase in the sheet resistance and a small decrease in the contact resistance. These changes can be explained by a twofold decrease in the diameter of the self-assembled fibers. These characteristics open the way to the use of furan- instead of thiophene-based analogues as non-natural side-chain modifications of peptides for electronic applications; this makes the fibrils more biodegradable and biorenewable.

BACKGROUND A study was conducted to assess for prognostic heterogeneity within the N2b and N2c classifications for oral cancer based on the number of metastatic lymph nodes and to determine whether laterality of neck disease provides additional prognostic information. METHODS An international multicenter study of 3704 patients with oral cancer undergoing surgery with curative intent was performed. The endpoints of interest were disease-specific survival and overall survival. Model fit was assessed by the Akaike Information Criterion and comparison of models with and without the covariate of interest using a likelihood ratio test. RESULTS The median number of metastatic lymph nodes was significantly higher in patients with N2c disease compared to those with N2b disease (P

Author(s): Amit, Moran; Chukoskie, Leanne; Skalsky, Andrew J; Garudadri, Harinath; Ng, Tse Nga

Rapid, on-site assessment is highly desirable in the fields of both medical treatment and novel robotics. To achieve this goal, our research aims to develop low-cost, flexible, large-area sensor devices for different health and environmental applications. In this presentation, we discuss case studies using similar pressure sensors for two different point-of-use applications: Autism spectrum disorder (ASD) motor skills characterization. There is no objective metric for evaluating motor skill training progress in autistic children, and current assessments rely on qualitative surveys. A common method used is a finger tapping test that requires videotaping and unreliable, time-consuming manual analysis, with large room for errors, even with computer vision analysis algorithms. We have fabricated an instrumented glove with touch sensors on textile for straightforward finger tapping patterns characterization. The results provide immediate objective feedback not only on the tapping counts, but on the temporal data (such as tapping duration and variation in duration) as well, which was not collected before. For the index finger tapping test, children with ASD perform less counts per minute compare to typically developing (TD) children. In addition, children with ASD tap their finger for an average longer duration, with larger variation between tap durations. In a 4 fingers tapping test children with ASD tend to have more irregular patterns and skip fingers compared to TD children. This glove could find future use for characterizing motor skills of people suffering from Parkinson’s disease, epilepsy seizures, and other neurological motor disorders. Robotic sensors for simultaneous pressure and organophosphate (OP) pesticide detection. There is an urgent need of sensor technologies to monitor hazardous materials for security and environmental applications. In particular, the occurrence of OP pesticide residues in agricultural products that poses a serious concern in the food and agriculture industries. Hence, rapid on-site detection of OPs through remote robotic sampling is highly desired to avoid placing people at exposure risks. To handle sample collection, the robotic manipulator requires tactile feedback, in order to ensure no damage will be done to either the robot or the other object in contact due to excessive force. To provide tactile feedback, pressure sensors based on capacitive mechanism were chosen. The sensitivity of the capacitive pressure sensors was tuned by adjusting the dielectric compressibility. Particularly, the sensitivity was increased by choosing softer materials, e. elastomers with low elastic modulus and porous structure that further lower elastic moduli of the foam dielectrics compared to solid films of the same material. We have combined low-cost chemical and pressure sensors together on disposable gloves, and demonstrated successive simultaneous tactile sensing and OP pesticide detection in a point-of-use platform that is scalable and economical.

Background Adenoid cystic carcinoma (ACC) is a locally aggressive tumor with a high prevalence of distant metastases. The purpose of this study was to identify independent predictors of outcome and to characterize the patterns of failure. Methods An international retrospective review was conducted of 489 patients with ACC treated between 1985 and 2011 in 9 cancer centers worldwide. Results Five-year overall-survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) were 76%, 80%, and 68%, respectively. Independent predictors of OS and DSS were: age, site, N classification, and presence of distant metastases. N classification, age, and bone invasion were associated with DFS on multivariate analysis. Age, tumor site, orbital invasion, and N classification were independent predictors of distant metastases. Conclusion The clinical course of ACC is slow but persistent. Paranasal sinus origin is associated with the lowest distant metastases rate but with the poorest outcome. These prognostic estimates should be considered when tailoring treatment for patients with ACC.

BACKGROUND An association between the survival of patients with oral cavity squamous cell carcinoma (OCSCC) and advancements in diagnosis and therapy has not been established. METHODS This was a retrospective, longitudinal, international, population-based study of 2738 patients who underwent resection of OCSCC during 2 different decades. Characteristics of patients from 7 international cancer centers who received treatment between 1990 and 2000 (group A; n = 735) were compared with patients who received treatment between 2001 and 2011 (group B; n = 2003). RESULTS Patients in group B had more advanced tumors and tended to develop distant metastases more frequently than patients in group A (P = .005). More group B patients underwent selective neck dissection and received adjuvant radiotherapy (P

Background: Lymph node density (LND) has previously been reported to reliably predict recurrence risk and survival in oral cavity squamous cell carcinoma (OSCC). This multicenter international study was designed to validate the concept of LND in OSCC. Methods: The study included 4254 patients diagnosed as having OSCC. The median follow-up was 41 months. Five-year overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), locoregional control and distant metastasis rates were calculated using the Kaplan–Meier method. Lymph node density (number of positive lymph nodes/total number of excised lymph nodes) was subjected to multivariate analysis. Results: The OS was 49% for patients with LND⩽0.07 compared with 35% for patients with LND>0.07 (P0.07 (P

Background This single-blinded, prospective, randomized controlled trial compared the efficacy and safety of an oxidized cellulose patch (Surgicel [Johnson and Johnson]) with conventional procedures for achieving hemostasis in thyroid surgery. Study Design The study included 190 patients scheduled for thyroidectomy. Patients were randomized into 1 conventionally treated (ligatures and bipolar electrocautery) group (n = 92) and a second group, which additionally received Surgicel (n = 98). Results The groups were demographically and clinically matched and had similar wound drainage volumes and mean duration of surgery. Postoperative bleeding rate was greater in the Surgicel group, yet the difference didn't reach statistical significance (p = 0.054). There were no significant group differences in postoperative wound infection, seroma, hypocalcemia, or recurrent laryngeal nerve palsy. Time to drain removal and length of hospital stay were significantly shorter in the conventional group (p Conclusions Routine use of an oxidized cellulose hemostatic agent has no advantage over conventional hemostasis and is potentially harmful in thyroid surgery.

Objectives/Hypothesis To demonstrate the feasibility of an anteriorly pedicled inferior turbinate flap (AITF) as a method for endoscopic reconstruction of anterior skull base defects in the absence of a nasal septal flap. Study Design Cadaveric feasibility study. Setting University-affiliated tertiary medical center. Materials and Patients A cadaveric model was used to investigate the feasibility of harvesting and skull base reconstruction with an AITF. The size and extent of coverage of the flap were investigated. Subsequently, defects resulting from an endoscopic resection of various anterior skull base pathologies were reconstructed with an AITF in patients. Results In the cadaveric model (n = 11), the mean length, width, and area of the AITFs were 4.76 ± 0.52 cm, 1.8 ± 0.34 cm, and 4.31 ± 0.87 cm2, respectively. The flap provided a mean of 111 ± 12% (range 95%–133%) coverage of the anterior skull base from the posterior table of the frontal sinus to the sella. Following that experience, ten patients were successfully reconstructed with AITFs, and there were no postoperative cerebrospinal fluid (CSF) leaks or occurrence of meningitis. Conclusion The results of this study demonstrate the feasibility of AITFs for the reconstruction of anterior skull base defects in the absence of alternative vascularized flaps. Level of Evidence N/A. Laryngoscope, 123:2940–2944, 2013