Method to generate a large cohort in-silico for type 1 diabetes.

BACKGROUND AND OBJECTIVE: In the last decade, several technological solutions have been proposed as artificial pancreas systems able to treat type 1 diabetes; most often they are built based on a control algorithm that needs to be validated before it is used with real patients. Control algorithms are usually tested with simulation tools that integrate mathematical models related mainly to the glucose-insulin dynamics, but other variables can be considered as well. In general, the simulators have a limited set of subjects. The main goal of this paper is to propose a new computational method to increase the number of virtual subjects, with physiological characteristics, included in the original mathematical models. METHODS: A subject is defined by a set of parameters given by a mathematical model. From the available reduced number of subjects in the model, the covariance of each parameter of every subject is obtained to establish a mathematical relationship. Then, new sets of parameters are calculated using linear regression methods; this generates larger cohorts, which allows for testing insulin therapies in open-loop or closed-loop scenarios. The new method proposed here increases the number of subjects in a virtual cohort using two versions of Hovorka's mathematical model. RESULTS: Two covariant cohorts are obtained with linear regression. Both cohorts are clustered to avoid overlapping in the glucose-insulin dynamics and are compared in terms of their qualitative and quantitative behaviours in the normoglycemic range. As a result, there have been generated two larger cohorts (256 subjects) than the original population, which contributes to improving the variability in in-silico tests. In addition, for analysing the characteristics of the covariant generation method, two random cohorts have been generated, where the parameters are obtained individually and independently from each other, exhibiting only distribution limitations so that these cohorts do not have physiological subjects. CONCLUSIONS: The proposed methodology has enabled the generation of a large cohort of 256 subjects, with different characteristics that are plausible in the T1DM population, significantly increasing the number of available subjects in existing mathematical models. The proposed methodology does not limit the number of subjects that can be generated and thus, it can be used to increase the number of cohorts provided by other mathematical models in diabetes, or even other scientific problems.

Automated Insulin Delivery: The Artificial Pancreas Technical Challenges.

BACKGROUND: The automation of glucose control has been an important goal of diabetes treatment for many decades. The first artificial pancreas experiences were in-hospital, closely supervised, small-scale, and short-term studies that demonstrated their superiority over continuous subcutaneous insulin infusion therapy. At present, long-term outpatient studies are being conducted in free-living scenarios. AREAS OF UNCERTAINTY: The integration of multiple devices increases patients' burden and the probability of technical risks. Control algorithms must be robust to manage disturbance variables, such as physical exercise, meal composition, stress, illness, and circadian variations in insulin sensitivity. Extra layers of safety could be achieved through remote supervision. Dual-hormone systems reduce the incidence and duration of hypoglycemia, but the availability of stable pumpable glucagon needs to be solved. Faster insulin analogues are expected to improve all types of artificial pancreas. THERAPEUTIC ADVANCES: Artificial pancreas safety and feasibility are being demonstrated in outpatient studies. Artificial pancreas use increases the time of sensor-measured glucose in near-normoglycemia and reduces the risk of hyperglycemia and hypoglycemia. The benefits are observed both in single- and dual-hormone algorithms and in full- or semi-closed loop control. A recent meta-analysis including 41 randomized controlled trials showed that artificial pancreas use achieves a reduction of time in hyperglycemia (2 hours less than control treatment) and in hypoglycemia (20 minutes less); mean levels of continuous glucose sensor fell by 8.6 mg/dL over 24 hours and by 14.6 mg/dL overnight. The OpenAPS community uses Do It Yourself artificial pancreas in the real world since 2013, and a recent retrospective cross-over study (n = 20) compared continuous glucose sensor readings before and after initiation: mean levels of blood glucose fell by 7.4 mg/dL over 24 hours and time in range increased from 75.8% to 82.2% (92 minutes more). CONCLUSIONS: The outpatient use of artificial pancreas is safe and improves glucose control in outpatients with type 1 diabetes compared with the use of any type of insulin-based treatment. The availability of open-source solutions and data sharing is needed to foster the development of new artificial pancreas approaches and to promote the wide use of Big Data tools for knowledge discovery, decision support, and personalization.

Decision Support in Diabetes Care: The Challenge of Supporting Patients in Their Daily Living Using a Mobile Glucose Predictor.

BACKGROUND: In type 1 diabetes mellitus (T1DM), patients play an active role in their own care and need to have the knowledge to adapt decisions to their daily living conditions. Artificial intelligence applications can help people with type 1 diabetes in decision making and allow them to react at time scales shorter than the scheduled face-to-face visits. This work presents a decision support system (DSS), based on glucose prediction, to assist patients in a mobile environment. METHODS: The system's impact on therapeutic corrective actions has been evaluated in a randomized crossover pilot study focused on interprandial periods. Twelve people with type 1 diabetes treated with insulin pump participated in two phases: In the experimental phase (EP) patients used the DSS to modify initial corrective decisions in presence of hypoglycemia or hyperglycemia events. In the control phase (CP) patients were asked to follow decisions without knowing the glucose prediction. A telemedicine platform allowed participants to register monitoring data and decisions and allowed endocrinologists to supervise data at the hospital. The study period was defined as a postprediction (PP) time window. RESULTS: After knowing the glucose prediction, participants modified the initial decision in 20% of the situations. No statistically significant differences were found in the PP Kovatchev's risk index change (-1.23 ± 11.85 in EP vs -0.56 ± 6.06 in CP). Participants had a positive opinion about the DSS with an average score higher than 7 in a usability questionnaire. CONCLUSION: The DSS had a relevant impact in the participants' decision making while dealing with T1DM and showed a high confidence of patients in the use of glucose prediction.

Artificial pancreas using a personalized rule-based controller achieves overnight normoglycemia in patients with type 1 diabetes.

OBJECTIVE: This study assessed the efficacy of a closed-loop (CL) system consisting of a predictive rule-based algorithm (pRBA) on achieving nocturnal and postprandial normoglycemia in patients with type 1 diabetes mellitus (T1DM). The algorithm is personalized for each patient's data using two different strategies to control nocturnal and postprandial periods. RESEARCH DESIGN AND METHODS: We performed a randomized crossover clinical study in which 10 T1DM patients treated with continuous subcutaneous insulin infusion (CSII) spent two nonconsecutive nights in the research facility: one with their usual CSII pattern (open-loop [OL]) and one controlled by the pRBA (CL). The CL period lasted from 10 p.m. to 10 a.m., including overnight control, and control of breakfast. Venous samples for blood glucose (BG) measurement were collected every 20 min. RESULTS: Time spent in normoglycemia (BG, 3.9-8.0 mmol/L) during the nocturnal period (12 a.m.-8 a.m.), expressed as median (interquartile range), increased from 66.6% (8.3-75%) with OL to 95.8% (73-100%) using the CL algorithm (P<0.05). Median time in hypoglycemia (BG, <3.9 mmol/L) was reduced from 4.2% (0-21%) in the OL night to 0.0% (0.0-0.0%) in the CL night (P<0.05). Nine hypoglycemic events (<3.9 mmol/L) were recorded with OL compared with one using CL. The postprandial glycemic excursion was not lower when the CL system was used in comparison with conventional preprandial bolus: time in target (3.9-10.0 mmol/L) 58.3% (29.1-87.5%) versus 50.0% (50-100%). CONCLUSIONS: A highly precise personalized pRBA obtains nocturnal normoglycemia, without significant hypoglycemia, in T1DM patients. There appears to be no clear benefit of CL over prandial bolus on the postprandial glycemia.

Meningitis aguda como inicio de un absceso hipofisario / Acute meningitis as the presenting symptom of a pituitary abscess

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A simulation study of an inverse controller for closed- and semiclosed-loop control in type 1 diabetes.

BACKGROUND: Closed-loop control algorithms in diabetes aim to calculate the optimum insulin delivery to maintain the patient in a normoglycemic state, taking the blood glucose level as the algorithm's main input. The major difficulties facing these algorithms when applied subcutaneously are insulin absorption time and delays in measurement of subcutaneous glucose with respect to the blood concentration. METHODS: This article presents an inverse controller (IC) obtained by inversion of an existing mathematical model and validated with synthetic patients simulated with a different model and is compared with a proportional-integral-derivative controller. RESULTS: Simulated results are presented for a mean patient and for a population of six simulated patients. The IC performance is analyzed for both full closed-loop and semiclosed-loop control. The IC is tested when initialized with the heuristic optimal gain, and it is compared with the performance when the initial gain is deviated from the optimal one (+/-10%). CONCLUSIONS: The simulation results show the viability of using an IC for closed-loop diabetes control. The IC is able to achieve normoglycemia over long periods of time when the optimal gain is used (63% for the full closed-loop control, and it is increased to 96% for the semiclosed-loop control).

Automatic data processing to achieve a safe telemedical artificial pancreas.

BACKGROUND: The use of telemedicine for diabetes care has evolved over time, proving that it contributes to patient self-monitoring, improves glycemic control, and provides analysis tools for decision support. The timely development of a safe and robust ambulatory artificial pancreas should rely on a telemedicine architecture complemented with automatic data analysis tools able to manage all the possible high-risk situations and to guarantee the patient's safety. METHODS: The Intelligent Control Assistant system (INCA) telemedical artificial pancreas architecture is based on a mobile personal assistant integrated into a telemedicine system. The INCA supports four control strategies and implements an automatic data processing system for risk management (ADP-RM) providing short-term and medium-term risk analyses. The system validation comprises data from 10 type 1 pump-treated diabetic patients who participated in two randomized crossover studies, and it also includes in silico simulation and retrospective data analysis. RESULTS: The ADP-RM short-term risk analysis prevents hypoglycemic events by interrupting insulin infusion. The pump interruption has been implemented in silico and tested for a closed-loop simulation over 30 hours. For medium-term risk management, analysis of capillary blood glucose notified the physician with a total of 62 alarms during a clinical experiment (56% for hyperglycemic events). The ADP-RM system is able to filter anomalous continuous glucose records and to detect abnormal administration of insulin doses with the pump. CONCLUSIONS: Automatic data analysis procedures have been tested as an essential tool to achieve a safe ambulatory telemedical artificial pancreas, showing their ability to manage short-term and medium-term risk situations.

BRAF mutation associated with other genetic events identifies a subset of aggressive papillary thyroid carcinoma.

PURPOSE: BRAF(V600E) mutation represents the most common oncogenic event in sporadic papillary thyroid cancer (PTC). There are, however, significant discrepancies regarding the overall frequency, its prevalence in PTC-variants, and its relationship with clinico-pathological parameters of poor outcome. Moreover, the impact of BRAF(V600E) mutants on tumour-related patient's death has not been evaluated. DESIGN: We analysed, by PCR-SSCP and/or PCR-direct sequencing, exons 8, 10, 11 and 15 of BRAF in 113 tumour samples from 49 PTC-patients. Matched lymph node metastases and/or distant metastases (DMs) were screened in 35 patients. Focal changes in the growth pattern or microscopic grade within the primary tumour (Pt) or the metastases were separately genotyped. Mutations at H-, K-, N-ras and PIK3CA exons 9 and 20 were also investigated. For comparison with PTC cases, the BRAF and Ras mutational status was evaluated in 89 specimens obtained from 24 poorly differentiated thyroid carcinomas (PDCs) and 36 anaplastic thyroid carcinomas (ATCs). RESULTS: BRAF(V600E) was found in 13/16 classical PTCs (CL-PTCs), 6/17 follicular variant PTCs (FV-PTCs) and 8/16 mixed (papillary/follicular) PTCs (Mx-PTCs), being significantly associated with CL-PTCs (P = 0.015). BRAF(V600E) segregated with metastatic PTC-cells in 43% of the patients, but only one DM disclosed the mutation. PTC-tumours featuring concurrent less-differentiated foci were BRAF wild-type in both components. Noteworthy, the frequency of BRAF mutations among PDCs and ATCs resulted considerably lower (16.6% and 25%, respectively) than in PTCs (55%). The prevalence of Ras mutations among PDCs and ATCs (46% and 36%, respectively) was, however, much higher than in PTCs (14%). Five (71%) of the patients who died of PTC displayed somatic mutations. Four of them had other gene alteration associated with BRAF(V600E) and the only one that did not, BRAF(V600E) was restricted to the Pt. The occurrence of BRAF(V600E) associated with other genetic events was an independent predictor of DMs during follow-up, recurrence and tumour-related death. Remarkably, two PDCs (8.3%) and five ATCs (14%) revealed concurrent BRAF and Ras mutations. CONCLUSION: BRAF(V600E)'alone' does not represent a marker for poor outcome, however, when associated with alterations in other genes identifies a subset of PTCs with increased risk of recurrence and decreased survival.

Definition of information technology architectures for continuous data management and medical device integration in diabetes.

The growing availability of continuous data from medical devices in diabetes management makes it crucial to define novel information technology architectures for efficient data storage, data transmission, and data visualization. The new paradigm of care demands the sharing of information in interoperable systems as the only way to support patient care in a continuum of care scenario. The technological platforms should support all the services required by the actors involved in the care process, located in different scenarios and managing diverse information for different purposes. This article presents basic criteria for defining flexible and adaptive architectures that are capable of interoperating with external systems, and integrating medical devices and decision support tools to extract all the relevant knowledge to support diabetes care.

High frequency of germline succinate dehydrogenase mutations in sporadic cervical paragangliomas in northern Spain: mitochondrial succinate dehydrogenase structure-function relationships and clinical-pathological correlations.

PURPOSE: Germline SDHB, SDHC, and/or SDHD mutations have been reported in familial and apparently sporadic paragangliomas (PGLs). There is, however, some variation in the prevalence, penetrance, and phenotypic expression of the succinate dehydrogenase (SDH) mutated gene among different populations. We sought to determine whether germline mutations in SDHB, SDHC, and/or SDHD play a role in cervical PGLs from northern Spain, where this disorder is particularly frequent, and whether there is any difference with respect to the data published in other populations. DESIGN: Thirty-six sporadic cervical PGLs and four familial PGLs were investigated by PCR-single-strand conformation polymorphism analysis and sequencing. Computational biology was applied to address the structural-conformational changes behind missense mutations and, simultaneously, infer the possible consequences in protein function. RESULTS: Eight sporadic cases (22.2%) carried pathogenic germline mutations, six of which were in SDHB and two in SDHD. Three families had mutations in SDHD and one in SDHB. Seven of 11 different pathogenic mutations (64%) affected SDHB. Ten mutations were novel. Missense mutations were primarily found in SDHB and frameshift mutations in SDHD. Missense SDHB mutations seemed to alter the enzymatic activity by hampering the electron transfer. SDH-linked tumors occurred mainly in males (P = 0.0033), occurred at a younger age (P < 0.0001), were usually multifocal (P = 0.0011), and exhibited a larger size (P = 0.0341). CONCLUSIONS: A significant proportion of sporadic cervical PGLs arise as a consequence of intrinsic genetic factors. At variance with previous reports, SDHB is frequently mutated in sporadic cervical PGLs and the mutations do not entail a deleterious behavior. Therefore, SDHB genetic testing may be considered in all subjects presenting with solitary cervical PGL and no family history.

Cuerpo extraño cervical: paciente afortunado / Cervical foreign body: a lucky patient

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Overexpression of focal adhesion kinase in head and neck squamous cell carcinoma is independent of fak gene copy number.

UNLABELLED: The development of human malignancies can involve the aberrant regulation of intracellular signal transduction pathways that regulate cell-extracellular matrix interactions. PURPOSE: In the current study, we aimed to evaluate focal adhesion kinase (FAK) at both genetic and protein expression levels in head and neck squamous cell carcinomas (HNSCC) and to explore the prognostic significance of FAK. EXPERIMENTAL DESIGN: A total of 211 tissue specimens, including 147 primary tumors, 56 lymph node metastases, 3 benign hyperplasias, and 5 dysplasias, were analyzed using immunohistochemistry. The fak gene dosage was determined in 33 tumors. Correlations among DNA, protein, and clinicopathologic variables were analyzed. RESULTS: FAK protein was overexpressed in HNSCCs compared with corresponding normal mucosa. High expression levels were found in 62% of the samples. Positive immunostaining was also detected in benign hyperplasias and preinvasive dysplastic lesions. All lymph node metastases examined showed FAK overexpression, with significant correlation with the expression in matched primary tumor. DNA copy number ratios for fak were higher in 39% of the tumors compared with normal mucosa. However, elevated FAK expression did not correlate with gains on DNA level, and not all cases with an amplification of the fak gene displayed protein overexpression. Similar data were obtained in five HNSCC-derived cell lines, in which FAK mRNA levels were precisely correlated with FAK protein levels. FAK protein overexpression in tumors correlated with nodal metastases. CONCLUSIONS: These findings suggest an involvement of FAK in the onset and progression of HNSCC and provide an insight into a mechanism of FAK activation alternative to gene amplification.

Annexin A1 expression in nasopharyngeal carcinoma correlates with squamous differentiation.

BACKGROUND: Alterations of annexin A1 (ANXA1) expression have been reported in various cancers. However, no data are available about the expression of this protein in nasopharyngeal carcinomas (NPCs). The objective of this study was to investigate the expression of ANXA1 in these tumors. METHODS: We examined noncancerous nasopharyngeal mucosa (4 cases) and NPC (20 cases) for ANXA1 expression using immunohistochemistry. RESULTS: All tumor tissues showed markedly reduced ANXA1 expression compared with a strong positive signal observed in the corresponding normal epithelia. We found that ANXA1 expression is associated with the histological type in NPC. Only squamous cell carcinomas presented a positive ANXA1 signal in differentiated areas whereas all poorly differentiated tumors exhibited negative staining. CONCLUSION: Our data show for the first time that ANXA1 expression is down-regulated in NPC and that its expression seems to be related with the squamous differentiation status of these tumors.

Mutation of the PIK3CA gene in anaplastic thyroid cancer.

The phosphatidylinositol 3'-kinase (PI3K) pathway is frequently activated in thyroid carcinomas through the constitutive activation of stimulatory molecules (e.g., Ras) and/or the loss of expression and/or function of the inhibitory PTEN protein that results in Akt activation. Recently, it has been reported that somatic mutations within the PI3K catalytic subunit, PIK3CA, are common (25-40%) among colorectal, gastric, breast, ovarian cancers, and high-grade brain tumors. Moreover, PIK3CA mutations have a tendency to cluster within the helical (exon 9) and the kinase (exon 20) domains. In this study, 13 thyroid cancer cell lines, 80 well-differentiated thyroid carcinomas of follicular (WDFC) and papillary (WDPC) type, and 70 anaplastic thyroid carcinomas (ATC) were investigated, by PCR-direct sequencing, for activating PIK3CA mutations at exons 9 and 20. Nonsynonymous somatic mutations were found in 16 ATC (23%), two WDFC (8%), and one WDPC (2%). In 18 of the 20 ATC cases showing coexisting differentiated carcinoma, mutations, when present, were restricted to the ATC component and located primarily within the kinase domain. Three cell lines of papillary and follicular lineage (K1, K2, and K5) were also found mutated. In addition, activation of Akt was observed in most of the ATC harboring PIK3CA mutations. These findings indicate that mutant PIK3CA is likely to function as an oncogene among ATC and less frequently well-differentiated thyroid carcinomas. The data also argue for a role of PIK3CA targeting in the treatment of ATC patients.

[Use of simultaneou free microvascular flap and pediculated flap for repairing in-depth defects]. / Utilización simultánea de colgajo libre microvascular y colgajo pediculado en la reparación de defectos de espesor total.

INTRODUCTION: In great surgical defects due to radical oncological head and neck surgery, sometimes, a unique flap reconstruction is not suitable to restore local anatomy. In those cases, it is suitable to do both, a free flap and a pectoralis major flap simultaneously. MATERIAL AND METHODS: We introduce a sample of 6 patients with local advanced head and neck cancer who underwent cervical surgery reconstruction with free foearm flap and pectoralis major myocutaneous flap simultaneously. RESULTS: In great surgical defects due to radical oncological head and neck surgery, sometimes, a unique flap reconstruction is not suitable to restore local anatomy. In those cases, it is suitable to do both, a free flap and a pectoralis major flap. Through and through defects (after oncological surgery), should need simultaneous skin and mucosa reconstruction thus cervical tissue contribution to cover the surgical defect. CONCLUSION: Simultaneous free flap and local flap reconstruction on one step surgery it is a reasonable option as we and other authors have done.

Utilización simultánea de colgajo libre microvascular y colgajo pediculado en la reparación de defectos de espesor total / Use of simultaneou free microvascular flap and pediculated flap for repairing in-depth defects

Introducción: En los grandes defectos quirúrgicos que en ocasiones provoca la cirugía oncológica radical, a veces, la adaptación de un único colgajo (libre o pediculado) es insuficiente para restablecer la anatomía locorregional. En estos casos es posible adaptar un colgajo libre y un colgajo pediculado en el mismo acto quirúrgico. Material y métodos: Presentamos una serie de 6 pacientes diagnosticados de cáncer de cabeza y cuello en estadio locorregional avanzado, a los que se realizó una reconstrucción del defecto quirúrgico masivo cervical mediante la utilización simultánea de un colgajo libre radial y un colgajo regional de pectoral mayor pediculado. Resultados: Definimos el concepto de defecto de espesor total (después de una cirugía oncológica), como aquel que exige la reconstrucción simultánea de piel y mucosa así como un mayor o menor volumen de tejido cervical. Conclusiones: Los defectos mucocutáneos o de espesor total son susceptibles de reparación quirúrgica con doble colgajo, a tenor de nuestros resultados y los de otros autores (AU)

INTRODUCTION: In great surgical defects due to radical oncological head and neck surgery, sometimes, a unique flap reconstruction is not suitable to restore local anatomy. In those cases, it is suitable to do both, a free flap and a pectoralis major flap simultaneously. MATERIAL AND METHODS: We introduce a sample of 6 patients with local advanced head and neck cancer who underwent cervical surgery reconstruction with free forearm flap and pectoralis major myocutaneous flap simultaneously. RESULTS: In great surgical defects due to radical oncological head and neck surgery, sometimes, a unique flap reconstruction is not suitable to restore local anatomy. In those cases, it is suitable to do both, a free flap and a pectoralis major flap. Through and through defects (after oncological surgery), should need simultaneous skin and mucosa reconstruction thus cervical tissue contribution to cover the surgical defect. CONCLUSION: Simultaneous free flap and local flap reconstruction on one step surgery it is a reasonable option as we and other authors have done (AU)

Expression of annexin A1 in normal and chronically inflamed nasal mucosa.

OBJECTIVE: To examine the expression pattern of annexin A1 in normal and chronically inflamed nasal mucosa to investigate its possible role in nasal inflammation. DESIGN: Immunohistochemical analysis. SUBJECTS: Samples of middle turbinates from 5 healthy subjects and 5 patients with perennial rhinitis, and samples of nasal polyps from 7 patients. INTERVENTIONS: Annexin A1 expression was examined with a standard immunohistochemical protocol on paraffin-embedded sections. RESULTS: Annexin A1 was highly expressed by ciliated cells, where it was concentrated on the apical surface and within the cilia. Goblet cells and nondifferentiated basal epithelial cells did not stain. In the glands of the lamina propria, intense staining was found in the cytoplasm and in the nuclei of the cells in the duct epithelium, whereas acinar cells did not stain. Intense cytoplasmic staining was observed in infiltrating polymorphonuclear cells and macrophages. No differences in the pattern or the level of expression of annexin A1 were found in the epithelial cells and glands of normal and chronically inflamed (perennial rhinitis or polyps) nasal mucosa. CONCLUSION: These results suggest that the expression of annexin A1 in respiratory epithelium of nasal mucosa is related to cell type and differentiation status of the cells and is not significantly altered by inflammatory diseases.

[Primary HIV drug resistance in a prison population. REPRICOVA-2 Study]. / Resistencias primarias de VIH en una población penitenciaria. Estudio REPRICOVA-2.

INTRODUCTION: Currently, there are few reports on primary human immunodeficiency virus (HIV) drug resistance in the prison population. METHODS: This is a descriptive, one-day prevalence study to identify HIV drug-resistant mutations in chronically infected treatment-naïve prisoners. Systematic randomized sampling was performed and genotyping was done by automatic sequencing. RESULTS: A total of 90 patients were studied. Two samples were found to have nucleoside reverse transcriptase inhibitor (NRTI)-resistant mutations, four had non-nucleoside reverse transcriptase inhibitor (NNRTI)-resistant mutations and one had protease inhibitor (PI)-resistant mutations. CONCLUSIONS: There was a low rate of primary resistance in our series. Therefore, resistance testing is not required before prescribing initial antiretroviral therapy in these patients.

Expression of E-cadherin, CD44s, and CD44v6 in laryngeal and pharyngeal carcinomas.

OBJECTIVE: Tumors arising from different sites of the head and neck area have very different clinical behavior. Loss or reduction of expression of adhesion molecules has been assumed to play a critical role in the development of head and neck carcinomas. The aim of this study is to determine if there are differences in the expression of adhesion molecules E-cadherin, CD44s, and CD44v6 in pharyngeal and laryngeal squamous-cell carcinomas. MATERIALS AND METHODS: E-cadherin, CD44s, and CD44v6 expression was determined by immunohistochemistry in paraffin-embedded tissue specimens from 72 patients with squamous-cell carcinoma, 37 of the pharynx and 35 of the larynx. RESULTS: Expression of CD44s was significantly lower in pharyngeal than in laryngeal tumors (P =.01). No differences in the expression of E-cadherin and CD44v6 were observed between these sites. CONCLUSIONS: These data suggest that there are some differences at molecular level between the different subsites of head and neck cancer.