Transoral lateral oropharyngectomy.

Based on a review of the indexed scientific medical literature, the authors document the key technical points, the errors to avoid, the limitations, indications and main oncologic and functional results when performing transoral lateral oropharyngectomy in cancer originating from the tonsillar region.

Biochemical markers in vascular cognitive impairment associated with subcortical small vessel disease - A consensus report.

BACKGROUND: Vascular cognitive impairment (VCI) is a heterogeneous entity with multiple aetiologies, all linked to underlying vascular disease. Among these, VCI related to subcortical small vessel disease (SSVD) is emerging as a major homogeneous subtype. Its progressive course raises the need for biomarker identification and/or development for adequate therapeutic interventions to be tested. In order to shed light in the current status on biochemical markers for VCI-SSVD, experts in field reviewed the recent evidence and literature data. METHOD: The group conducted a comprehensive search on Medline, PubMed and Embase databases for studies published until 15.01.2017. The proposal on current status of biochemical markers in VCI-SSVD was reviewed by all co-authors and the draft was repeatedly circulated and discussed before it was finalized. RESULTS: This review identifies a large number of biochemical markers derived from CSF and blood. There is a considerable overlap of VCI-SSVD clinical symptoms with those of Alzheimer's disease (AD). Although most of the published studies are small and their findings remain to be replicated in larger cohorts, several biomarkers have shown promise in separating VCI-SSVD from AD. These promising biomarkers are closely linked to underlying SSVD pathophysiology, namely disruption of blood-CSF and blood-brain barriers (BCB-BBB) and breakdown of white matter myelinated fibres and extracellular matrix, as well as blood and brain inflammation. The leading biomarker candidates are: elevated CSF/blood albumin ratio, which reflects BCB/BBB disruption; altered CSF matrix metalloproteinases, reflecting extracellular matrix breakdown; CSF neurofilment as a marker of axonal damage, and possibly blood inflammatory cytokines and adhesion molecules. The suggested SSVD biomarker deviations contrasts the characteristic CSF profile in AD, i.e. depletion of amyloid beta peptide and increased phosphorylated and total tau. CONCLUSIONS: Combining SSVD and AD biomarkers may provide a powerful tool to identify with greater precision appropriate patients for clinical trials of more homogeneous dementia populations. Thereby, biomarkers might promote therapeutic progress not only in VCI-SSVD, but also in AD.

Estudio descriptivo del síndrome de burnout en becados de psiquiatría / Burnout syndrome in psychiatry residents: a descriptive study

El síndrome burnout se define como una respuesta a un estrés emocional crónico, cuyos rasgos principales son el agotamiento físico y psicológico, una actitud fría y despersonalizada en la relación con los demás y un sentimiento de inadecuación en las tareas que se han de realizar. Actualmente es entendido como un problema social y de salud pública, que daña la calidad de vida de la persona que lo padece y disminuye la calidad asistencial. Considerando la alta carga emocional que supone el contacto permanente con dificultades de salud mental, este estudio tiene como objetivo explorar los niveles de riesgo de desgaste profesional en un grupo de médicos cursando el programa de especialidad en psiquiatría. Se aplicó la encuesta Maslach Burnout Inventory (MBI) a un total de 22 becados de psiquiatría de la Clínica Psiquiátrica Universitaria (en septiembre 2010), y se registraron las características demográficas para el análisis posterior. Los puntajes promedio obtenidos en las subescalas de agotamiento Emocional, Despersonalización, y Logros Personales se analizan para distintos subgrupos de acuerdo a las características demográficas estudiadas (género, estado civil, experiencia previa, programa de formación y año de beca).

The Cervical Spinal Canal Tapers Differently in Patients with Chiari I with and without Syringomyelia.

BACKGROUND AND PURPOSE: The cause of syringomyelia in patients with Chiari I remains uncertain. Cervical spine anatomy modifies CSF velocities, flow patterns, and pressure gradients, which may affect the spinal cord. We tested the hypothesis that cervical spinal anatomy differs between Chiari I patients with and without syringomyelia. MATERIALS AND METHODS: We identified consecutive patients with Chiari I at 3 institutions and divided them into groups with and without syringomyelia. Five readers measured anteroposterior cervical spinal diameters, tonsillar herniation, and syrinx dimensions on cervical MR images. Taper ratios for C1-C7, C1-C4, and C4-C7 spinal segments were calculated by linear least squares fitting to the appropriate spinal canal diameters. Mean taper ratios and tonsillar herniation for groups were compared and tested for statistical significance with a Kruskal-Wallis test. Inter- and intrareader agreement and correlations in the data were measured. RESULTS: One hundred fifty patients were included, of which 49 had syringomyelia. C1-C7 taper ratios were smaller and C4-C7 taper ratios greater for patients with syringomyelia than for those without it. C1-C4 taper ratios did not differ significantly between groups. Patients with syringomyelia had, on average, greater tonsillar herniation than those without a syrinx. However, C4-C7 taper ratios were steeper, for all degrees of tonsil herniation, in patients with syringomyelia. Differences among readers did not exceed differences among patient groups. CONCLUSIONS: The tapering of the lower cervical spine may contribute to the development of syringomyelia in patients with Chiari I.

Changes of circulatory-metabolic indices and skull biomechanics with brain activity during aging.

The cerebral blood flow values used in experimental and clinical investigations as the informative criteria for brain blood supply are often misleading. The correlation between the cerebral blood supply and brain function is not proven in all cases. An increase of brain activity is known to be accompanied by a rise of blood flow in activated regions, while a decreased activity results in a decreased blood flow. This demonstrates the close correlation between the brain blood supply and its activity. Such a correlation had not been noted in the age-dependent decrease of cerebral blood flow, suggesting the existence of special age-related mechanisms that develop with age to maintain brain metabolism. The biomechanical properties are of special significance as predicted in the early 20th century. Only recently were they validated by the simultaneous recording of Transcranial Dopplerogram and Rheoencephalogram with in-depth analysis focused on single cardiac cycles. Functioning of the intracranial blood and cerebrospinal fluid dynamics was integrated with a special physiological test "Prognosis-2" to measure brain cognitive function. Correlation was demonstrated with the circulatory-metabolic state of brain activity, especially in people with changing cognitive function. The data supports a conceptual model of adequate circulatory-metabolic supply of brain activity, showing the functional unity, which follows from integration of the mentioned systems.

Prediction of disease-free survival in patients with squamous cell carcinomas of the head and neck using dynamic contrast-enhanced MR imaging.

BACKGROUND AND PURPOSE: Patients with HNSCC have a poor prognosis and development of imaging biomarkers that predict long-term outcome might aid in planning optimal treatment strategies. Therefore, the purpose of the present study was to predict disease-free survival in patients with HNSCC by using pretreatment K(trans) measured from dynamic contrast-enhanced MR imaging. MATERIALS AND METHODS: Sixty-six patients with HNSCC were recruited from January 2005 to October 2008. Three patients were excluded because they underwent upfront neck dissection, and 6 patients were excluded due to suboptimal MR imaging data or being lost to follow-up. Disease-free survival was measured in the remaining 57 patients from the end date of chemoradiation therapy. In patients who died, the end point was the date of death, while in surviving patients the date of last clinical follow-up was used as the end point. Pretreatment K(trans) and nodal volume were computed from the largest metastatic node, and median pretreatment K(trans) and volume were used to divide patients into 2 groups (at or above the threshold value [group I] and below the threshold value [group II]. Disease-free survival was analyzed by the Kaplan-Meier method, and the results were compared by using a logrank test with K(trans) and nodal volume as predictors. A P value <.05 was considered significant. RESULTS: Thirteen of 57 patients had died of HNSCC by the last follow-up period (March 31, 2009). Patients with higher pretreatment K(trans) values had prolonged disease-free survival compared with patients with lower K(trans) values (P=.029). However, there was no significant difference in disease-free survival when nodal volume was used as a predictor (P=.599). CONCLUSIONS: Pretreatment K(trans) may be a useful prognostic marker in HNSCC.

Injection augmentation of arytenoids after partial laryngectomy: case series.

BACKGROUND: We undertook collagen injection laryngoplasty to achieve arytenoid augmentation in patients with dysphagia and persistent aspiration following partial laryngectomy, and we evaluated the efficacy of arytenoid augmentation in aiding neoglottic closure and ensuring airway safety. METHODS: Two patients with persistent swallowing impairment after partial laryngectomy were studied. Swallowing was evaluated using fibre-optic endoscopy, and modified barium swallow study. Collagen was then injected into the arytenoid mucosa to achieve neoglottic competence. RESULTS: The patients were followed up for up to two years. Both patients showed a marked improvement in neoglottic competence, as evaluated by fibre-optic and flexible endoscopy at three-month and one-year follow-up appointments. CONCLUSION: Arytenoid augmentation by injection laryngoplasty can be considered a safe and effective surgical tool for the treatment of dysphagia with persistent aspiration following partial laryngectomy.

Evidence for mesenchymal-like sub-populations within squamous cell carcinomas possessing chemoresistance and phenotypic plasticity.

Variable drug responses among malignant cells within individual tumors may represent a barrier to their eradication using chemotherapy. Carcinoma cells expressing mesenchymal markers resist conventional and epidermal growth factor receptor (EGFR)-targeted chemotherapy. In this study, we evaluated whether mesenchymal-like sub-populations within human squamous cell carcinomas (SCCs) with predominantly epithelial features contribute to overall therapy resistance. We identified a mesenchymal-like subset expressing low E-cadherin (Ecad-lo) and high vimentin within the upper aerodigestive tract SCCs. This subset was both isolated from the cell lines and was identified in xenografts and primary clinical specimens. The Ecad-lo subset contained more low-turnover cells, correlating with resistance to the conventional chemotherapeutic paclitaxel in vitro. Epidermal growth factor induced less stimulation of the mitogen-activated protein kinase and phosphatidylinositol-3-kinase pathways in Ecad-lo cells, which was likely due to lower EGFR expression in this subset and correlated with in vivo resistance to the EGFR-targeted antibody, cetuximab. The Ecad-lo and high E-cadherin subsets were dynamic in phenotype, showing the capacity to repopulate each other from single-cell clones. Taken together, these results provide evidence for a low-turnover, mesenchymal-like sub-population in SCCs with diminished EGFR pathway function and intrinsic resistance to conventional and EGFR-targeted chemotherapies.

Prediction of response to chemoradiation therapy in squamous cell carcinomas of the head and neck using dynamic contrast-enhanced MR imaging.

BACKGROUND AND PURPOSE: Tumor microenvironment, including blood flow and permeability, may provide crucial information regarding response to chemoradiation therapy. Thus, the objective of this study was to investigate the efficacy of pretreatment DCE-MR imaging for prediction of response to chemoradiation therapy in HNSCC. MATERIALS AND METHODS: DCE-MR imaging studies were performed on 33 patients with newly diagnosed HNSCC before neoadjuvant chemoradiation therapy by using a 1.5T (n = 24) or a 3T (n = 9) magnet. The data were analyzed by using SSM for estimation of K(trans), v(e), and tau(i). Response to treatment was determined on completion of chemoradiation as CR, with no evidence of disease (clinically or pathologically), or PR, with pathologically proved residual tumor. RESULTS: The average pretreatment K(trans) value of the CR group (0.64 +/- 0.11 minutes(-1), n = 24) was significantly higher (P = .001) than that of the PR (0.21 +/- 0.05 minutes(-1), n = 9) group. No significant difference was found in other pharmacokinetic model parameters: v(e) and tau(i), between the 2 groups. Although the PR group had larger metastatic nodal volume than the CR group, it was not significantly different (P = .276). CONCLUSIONS: These results indicate that pretreatment DCE-MR imaging can be potentially used for prediction of response to chemoradiation therapy of HNSCC.

[Age-related characteristics of relationships between brain blood flow, liquor dynamics and biomechanical properties of human cranium].

The peculiarities of relationships between changes of cerebral blood flow, intracranial liquor dynamics and skull biomechanics in humans were studied in an age aspect. For this aim, a non-invasive method was proposed based on concomitant registration of rheoencephalogram and transcranial dopplerogram and evaluation of relationships between intracranial volume and pulse pressure changes (P-V index). The data obtained were analyzed by pattern-phase computer processing and compared with the blood flow parameters. The investigation was carried out on healthy volunteers of 18-25, 40-50 and 65-75 years of age. It was shown that circulatory-metabolic supplying of human brain was supported by such factors as volume brain blood flow, intracranial liquor dynamics in cooperation with skull biomechanics. The cerebral blood flow decrease at aging could be compensated by increase of the reserve-compensatory abilities of the system of cranial-spinal liquor dynamics.

Topical kinetin 0.1% lotion for improving the signs and symptoms of rosacea.

Many patients with rosacea are unable to tolerate extended treatment periods with topical agents because of the unusually high skin sensitivity that often accompanies rosacea. Kinetin (N(6)-furfuryladenine) is a plant cytokinin that reportedly helps restore skin barrier function and may be useful to ameliorate the signs and symptoms of rosacea. The purpose of this open-label study was to determine the tolerance and efficacy of twice-daily application of kinetin 0.1% lotion for improving the signs and symptoms of mild to moderate facial rosacea. Subjects applied kinetin 0.1% lotion twice daily to the face, with daily use of a sunscreen of sun protection factor 30. Subjects were evaluated at baseline and at 4-week intervals for 12 weeks to assess efficacy and tolerance. Results of this study suggest that kinetin 0.1% lotion is a well-tolerated moisturizing lotion option for subjects with mild to moderate inflammatory rosacea.

'Keratolytic' properties of benzoyl peroxide and retinoic acid resemble salicylic acid in man.

OBJECTIVES: Retinoic acid (RA) and benzoyl peroxide (BP) were studied, comparing their keratolytic efficacy and water barrier disruption to that of salicylic acid (SA), a well-established keratolytic, under similar conditions. PATIENTS/METHODS: Six volunteers were included in this blinded study. Eleven randomized test sites were marked on the volar forearms, containing sites for untreated skin at time zero, unoccluded, occlusion, and vehicle controls for 3 and 6 h, and each of BP, RA, and SA solutions for 3 and 6 h. At each time point, occlusion at 5 of the test sites was removed, and chromameter measurements were performed over 30 min. Each site then underwent 25 stratum corneum (SC) tape strippings. At 1, 5, and 30 min after the last stripping at each site, TEWL measurements were performed. Quantitative protein analysis of the SC from the tapes was then performed. RESULTS AND CONCLUSION: after 3 h, bp was significantly more effective in disrupting sc cohesion than sa and ra, indicating bp is a moderate keratolytic agent in addition to its antimicrobial properties. After 6 h, all three agents were similarly effective in keratolysis. Barrier disruption, as measured by TEWL, paralleled depth of SC removal. SA tended to exhibit the greatest keratolytic efficacy superficially, hence its clinical effectiveness in superficial conditions such as comedonal acne, whereas BP was more effective at deeper levels, complimenting its antimicrobial effects and enabling it to treat deeper, more inflammatory lesions. None of the agents significantly affected skin erythema. These techniques provide a robust and rapid assay for in vivo keratolytic demonstration.

Molecular cytogenetic parameters in fibroblasts of ataxia telangiectasia carrier.

Ataxia telangiectasia (AT) is a pleiotropic and rare (1:40,000 to 1:100,000) recessive disease. Laboratory investigations have failed to detect any consistent anomaly in cells from AT heterozygotes. To estimate random aneuploidy, we applied a fluorescence in situ hybridization technique with alpha-satellite probes for chromosomes 8 and 9 and replication pattern for RB-1, HER-2/neu, and the imprinted SNRPN loci on primary AT carrier fibroblasts. Higher random aneuploidy was not found in the carrier fibroblasts compared to control amniocytic cells. The asynchrony pattern was higher in the AT carrier cells with the RB-1 locus (P=0.057) and significantly higher with the HER-2/neu locus (P < 0.001) compared to control cells. As for the imprinted locus SNRPN, there was a significantly lower asynchrony rate in the AT carriers (P < 10(-5)) compared to the control group. Molecular cytogenetic parameters of random aneuploidy and replication pattern may reflect predisposition for the development of cancer. It is possible that in some AT carriers the genetic instability phenomena associated with the abnormal replication pattern may represent their potential for developing malignancies.

Molecular cytogenetic parameters in fibroblasts from patients and carriers of xeroderma pigmentosum.

Xeroderma pigmentosum (XP) is a rare autosomal recessive syndrome. Laboratory investigations have failed to detect any consistent anomaly in cells from XP heterozygotic subjects, although examples of behavior intermediate between normal and XP cells have been reported. To estimate random aneuploidy we applied fluorescence in situ hybridization (FISH) with alpha-satellite probes for chromosomes 8 and 9 and replication pattern for TP53 (p53), ERBB2 (HER-2/neu), and MYCN (N-MYC) loci and for the imprinted SNRPN locus. A significantly higher rate of aneuploidy rate was observed in XP patients and carriers than in controls. The asynchrony pattern was significantly higher in XP carriers and patients with all three coding loci analyzed and significantly lower in XP patients and carriers with the imprinted locus SNRPN than in the control group. Molecular cytogenetic parameters such as random aneuploidy and replication pattern, which are known to reflect chromosomal instability, may be part of the tumorigenesis process. In XP patients and carriers, this genetic instability may represent a potential for developing malignancies.

Tazarotene cream for the treatment of facial photodamage: a multicenter, investigator-masked, randomized, vehicle-controlled, parallel comparison of 0.01%, 0.025%, 0.05%, and 0.1% tazarotene creams with 0.05% tretinoin emollient cream applied once daily for 24 weeks.

OBJECTIVE: To assess the safety and efficacy of 4 concentrations of tazarotene cream in the treatment of facial photodamage. DESIGN: Prospective weekly multicenter, investigator-masked, randomized, parallel-group study. SETTING: University hospitals and clinical research centers. PATIENTS: Three hundred forty-nine subjects with facial photodamage. INTERVENTION: Daily topical application of tazarotene cream (0.01%, 0.025%, 0.05%, and 0.1%) compared with its vehicle and with 0.05% tretinoin emollient cream. RESULTS: Tazarotene cream and tretinoin cream significantly improved mottled hyperpigmentation and fine wrinkles. At week 24, treatment success rates based on global responses were 67% (39 of 58 subjects) with 0.1% tazarotene, 52% (30 of 58 subjects) with 0.05% tazarotene, 36% (21 of 58 subjects) with 0.025% tazarotene, 41% (24 of 59 subjects) with 0.01% tazarotene, 55% (32 of 58 subjects) with 0.05% tretinoin, and 22% (13 of 58 subjects) with vehicle. Local adverse events, although more frequent with tazarotene at higher concentrations, were generally mild to moderate. CONCLUSIONS: Tazarotene in a cream formulation is safe and is associated with positive changes in the treatment of photodamaged facial skin.

Feasibility and outcome of endoscopic staple-assisted esophagodiverticulostomy for Zenker's diverticulum.

OBJECTIVES/HYPOTHESIS: Endoscopic staple-assisted esophagodiverticulostomy (ESED) is a newly described method of surgically correcting Zenker's diverticulum. Initial reports on the ease and success of the surgery have been quite enthusiastic, making it seem the procedure of choice. We initiated the procedure in an algorithm of treatment of Zenker's diverticulum, to further explore the feasibility and outcome of this new technique. STUDY DESIGN: This is a case series of 23 patients with Zenker's diverticulum who have undergone surgical repair. For each patient, an attempt at ESED was made. If unsuccessful, an open approach was then taken. RESULTS: Seven of 23 patients (30%) were unable to be treated with ESED because of inability to expose the diverticulum or unfavorable anatomy of the diverticulum itself. Of the remaining 16 patients, ESED was successful in resolving the symptoms of diverticulum in 14 (87%). Two patients (13%) were somewhat improved but had persistent dysphagia. No significant complications occurred. All patients resumed oral diet within the first 24 hours after surgery. CONCLUSION: Esophagodiverticulostomy is an excellent method of surgically correcting Zenker's diverticulum in many patients, but anatomical considerations may prevent its use, making open approaches of continued importance in a surgeon's armamentarium.

Fetal cells in the uterine cervix: a source for early non-invasive prenatal diagnosis.

Various non-invasive techniques for prenatal diagnosis have been under investigation. We evaluated the success of fetal sexing using a non-invasive technique for obtaining fetal cells, uterine cervix brushing, in combination with FISH. Thirty pregnant women who completed between 6 and 10 weeks of gestation and who were scheduled to undergo pregnancy termination were included in the study. A Pap smear cytobrush was inserted through the external os to a maximum depth of 2 cm and removed while rotating it a full turn. The material that was caught on the brush was spread on four microscope slides. Two-color FISH was used for fetal sexing. Following pregnancy termination, a placental sample was used for full karyotyping. In 29/30 cases FISH diagnosis was confirmed by chromosomal analysis. The only male case in which a Y chromosome was not seen was from a pregnancy of 6 weeks 6 days gestational age. One case was mosaic of 46,XY/47,XXY (25%). In most cases (7/13) the Y chromosome was already identified in the first analyzed slide. With the use of a cytobrush fetal cells can be easily obtained for the purpose of prenatal diagnosis of chromosomal disorders.

Advanced oropharyngeal carcinoma treated with surgery and radiotherapy: oncologic outcome and functional assessment.

INTRODUCTION/PURPOSE: Surgery and postoperative radiotherapy (XRT) is a standard therapy for locally advanced resectable oropharyngeal carcinoma. This maximizes local-regional control, but does not address the potential for occult distant metastases. Additionally, some patients may suffer poor functional outcome after this intensive local therapy. This report reviews our institutional experience with modern radical surgery and XRT for this disease. METHODS: A retrospective chart review was performed on 51 consecutive patients treated from 1991 to 1997 at the University of Pennsylvania with radical surgery and postoperative XRT. This study included patients with locally advanced, stage III/IV (exclusive of T1-2N1) squamous carcinoma of the oropharynx. All patients had a good performance status (ECOG 0-1). Patients who received adjuvant chemotherapy were excluded. No patient had gross residual disease after surgery; the median XRT dose was 63.7 Gy. Survival, local-regional control (LRC), and freedom from distant metastases (DM) were calculated actuarially. In patients who remained free of disease, functional status was determined using the List Performance Status Scale (PSS). RESULTS: With a median follow-up in surviving patients of 34 months, the 3-year actuarial overall survival was 51%. The 3-year LRC was 73%, and the freedom from DM was 69%. The most significant factor predicting for failure was the number of pathologically positive nodes (P <.001 for survival and DM; P =.003 for LRC). In 29 patients who were evaluable for the List PSS, the mean normalcy-of-diet score was 48; the mean eating-in-public score was 53; and the mean understandability-of-speech score was 75. There was a trend toward better PSS scores in patients with T1-2 tumors versus T3-4 tumors, although this did not reach statistical significance. CONCLUSIONS: Surgery and postoperative XRT offer relatively good LRC and moderate overall survival rates. Results, however, remain suboptimal, particularly with respect to the risk of DM and the functional outcome. These data provide a baseline for comparison with maturing results from multimodality trials in which radical surgery is not used in all patients with locally advanced oropharyngeal carcinoma.