RESUMEN
BACKGROUND: Bladder drainage is systematically used in rectal cancer surgery; however, the optimal type of drainage, transurethral catheterization (TUC) or suprapubic catheterization (SPC), is still controversial. The aim was to compare the rates of urinary tract infection on the fourth postoperative day (POD4) between TUC and SPC, after rectal cancer surgery regardless of the day of removal of the urinary drain. METHODS: This randomized clinical trial in 19 expert colorectal surgery centers in France and Belgium was performed between October 2016 and October 2019 and included 240 men (with normal or subnormal voiding function) undergoing mesorectal excision with low anastomosis for rectal cancer. Patients were followed at postoperative days 4, 30, and 180. RESULTS: In 208 patients (median age 66 years [IQR 58-71]) randomized to TUC (n = 99) or SPC (n = 109), the rate of urinary infection at POD4 was not significantly different whatever the type of drainage (11/99 (11.1%) vs. 8/109 (7.3%), 95% CI, - 4.2% to 11.7%; p = 0.35). There was significantly more pyuria in the TUC group (79/99 (79.0%) vs. (60/109 (60.9%), 95% CI, 5.7-30.0%; p = 0.004). No difference in bacteriuria was observed between the groups. Patients in the TUC group had a shorter duration of catheterization (median 4 [2-5] vs. 4 [3-5] days; p = 0.002). Drainage complications were more frequent in the SPC group at all followup visits. CONCLUSIONS: TUC should be preferred over SPC in male patients undergoing surgery for mid and/or lower rectal cancers, owing to the lower rate of complications and shorter duration of catheterization. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02922647.
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Drenaje , Complicaciones Posoperatorias , Neoplasias del Recto , Cateterismo Urinario , Infecciones Urinarias , Humanos , Masculino , Neoplasias del Recto/cirugía , Persona de Mediana Edad , Anciano , Cateterismo Urinario/métodos , Cateterismo Urinario/efectos adversos , Drenaje/métodos , Infecciones Urinarias/etiología , Infecciones Urinarias/prevención & control , Infecciones Urinarias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Vejiga Urinaria/cirugía , BélgicaRESUMEN
BACKGROUND: Dental caries is considered a major global health issue and among the most challenging diseases worldwide. An effective way of preventing dental caries is the fissure sealant (FS) therapy. OBJECTIVE: To determine the effectiveness of an educational intervention developed based on the health belief model (HBM) for parents' perception of FS therapy for their children. METHODS: Quasi-experiment among 300 parents of 6-12 year-old children, 150 in the intervention group (IG) and 150 in the control (CG), in the south of Iran recruited via both clustering and convenience sampling. Data were collected using a validated questionnaire collecting demographic information, knowledge and data on HBM constructs and FS behaviour. Eight intervention sessions, 40-60 minutes long, were held for over month. The primary outcome was child's receipt of fissure sealants 3 months after the intervention. RESULTS: The two groups had similar knowledge and the HBM constructs at baseline. After the intervention, the receipt of FS therapy was 65% and 12% in the IG and CG, respectively (p ⟨ 0.001, Chi Sq.). ANCOVA supported post-test differences between the intervention and control groups when accounting for baseline scores (p⟨0.05). CONCLUSIONS: The educational HBM-based intervention improved parents' perceptions and their children's receipt of FS therapy. The intervention affected the HBM constructs. Barriers to healthy oral/dental behaviours may be reduced by interventions at multiple layers (beyond the individual level).
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Caries Dental , Humanos , Niño , Caries Dental/prevención & control , Selladores de Fosas y Fisuras/uso terapéutico , Encuestas y Cuestionarios , Padres , PercepciónRESUMEN
PURPOSE: Anastomotic leak is a dreaded complication of colorectal surgery. An endoscopic grading score of the perianastomotic mucosa has been previously developed at our institution (UCI) to assess colorectal anastomotic integrity. The objective of this study is to validate the UCI anastomotic score and determine its impact in anastomotic failure. METHODS: As a follow-up study of the UCI grading score implementation during 2011 to 2014, patients undergoing stapled colorectal anastomoses after sigmoidectomy or proctectomy at a single institution from 2015 to 2018 were retrospectively reviewed. Patients were grouped into three tiers based on endoscopic appearance (grade 1, circumferentially normal mucosa; grade 2, ischemia/congestion < 30% of circumference; grade 3, ischemia/congestion > 30% of circumference). RESULTS: On the basis of endoscopic mucosal evaluation, grade 1 anastomosis was observed in 299 patients (94%), grade 2 anastomosis in 14 patients (4.4%), and grade 3 anastomosis in 5 patients (1.6%). All grade 3 classifications were immediately and successfully revised intraoperatively with reclassification as a grade 1 anastomosis. The anastomotic leak rate of the follow-up study period from 2015 to 2018 was 6.4% which was lower compared to the anastomotic leak rate of 12.2% in the original study period from 2011 to 2014 (p = 0.07). Anastomotic leak rate for the entire patient series was 8.5%. A grade 2 anastomosis was associated with higher anastomotic leak rate compared to a grade 1 anastomosis (35.7% vs. 7.4%, p < 0.05). None of the five grade 3 anastomoses resulted in an anastomotic leak upon revision. CONCLUSION: This study further validates the anastomotic grading score and suggests that its systematic implementation can result in a reduction in anastomotic leaks.
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Fuga Anastomótica , Neoplasias Colorrectales , Humanos , Fuga Anastomótica/diagnóstico , Fuga Anastomótica/etiología , Estudios de Seguimiento , Estudios Retrospectivos , Anastomosis Quirúrgica/efectos adversos , Anastomosis Quirúrgica/métodos , Neoplasias Colorrectales/complicaciones , IsquemiaRESUMEN
BACKGROUND: Adjuvant chemotherapy (AC) after neoadjuvant chemoradiation and surgical resection has been the standard of care for locally advanced rectal cancer. However, there are no evidence-based guidelines regarding the optimal timing of AC for rectal cancer. The objective of this study was to evaluate the effect of AC timing on overall survival for rectal cancer. METHODS: The National Cancer Database (NCDB) from 2004 to 2016 was queried for primary clinical stage II or III rectal cancer patients who had undergone neoadjuvant chemoradiation followed by surgery and AC. Patients were grouped based on AC initiation: early ≤ 4 weeks, intermediate 4-8 weeks, and delayed ≥ 8 weeks. The primary outcome was overall survival. RESULTS: We identified 8722 patients, of which 905 (10.4%) received early AC, 4621 (53.0%) intermediate AC, and 3196 (36.6%) delayed AC. Pathological lymph-node metastasis (ypN +) was positive in 73% of early AC, 74% intermediate AC, and 63% delayed AC (p < 0.05). The 5-year survival probability was 71.1% (95% CI 68-74%) for early AC, 73.2% (95% CI 72-75%) intermediate AC, and 65.8% (95% CI 64-68%) delayed AC (p < 0.001). Using Cox proportional hazard modeling, patients undergoing delayed AC had an associated decreased survival compared to patients receiving early AC (HR 1.18; 95% CI 1.028-1.353, p = 0.018) or intermediate AC (HR 1.28; 95% CI 1.179-1.395, p < 0.01). CONCLUSIONS: Delay in AC administration may be associated with decreased 5-year survival. Compared to early or intermediate AC, patients in the delayed AC group were observed to have increased risk of death, despite having lower proportions with ypN + disease. Patients with higher socioeconomic and education status were more likely to receive early chemotherapy.
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Terapia Neoadyuvante , Neoplasias del Recto , Humanos , Quimioterapia Adyuvante , Quimioradioterapia , Neoplasias del Recto/patología , Bases de Datos Factuales , Estudios Retrospectivos , Estadificación de NeoplasiasRESUMEN
BACKGROUND: Tumour extension beyond the mesorectal plane (ymrT4) occurs in 5-10 per cent of patients with rectal cancer and 10 per cent of patients develop locally recurrent rectal cancer (LRRC) after primary surgery. There is global variation in healthcare delivery for these conditions. METHODS: An international benchmark trial of the management of ymrT4 tumours and LRRC was undertaken in France and Australia between 2015 and 2017. Heterogeneity in management and operative decision-making were analysed by comparison of surgical resection rates, blinded intercountry reading of pelvic MRI, quality-of-life assessment and qualitative evaluations. RESULTS: Among 154 patients (97 in France and 57 in Australia), 31·8 per cent had ymrT4 disease and 68·2 per cent LRRC. The surgical resection rates were 88 and 79 per cent in France and Australia respectively (P = 0·112). The concordance in operative planning was low (κ = 0·314); the rate of pelvic exenteration was lower in France than Australia both in clinical practice (36 of 78 versus 34 of 40; P < 0·001) and in theoretical conditions (10 of 25 versus 50 of 57; P = 0·002). The R0 resection rate was lower in France than Australia for LRRC (25 of 49 versus 18 of 21; P = 0·007) but not for ymrT4 tumours (21 of 26 versus 15 of 15; P = 0·139). Morbidity rates were similar. Patients who underwent non-exenterative procedures had higher scores on the mental functioning subscale at 12 months (P = 0·047), and a lower level of distress at 6 months (P = 0·049). Qualitative analysis highlighted five categories of psychosocial factors influencing treatment decisions: patient, strategy, specialist, organization and culture. CONCLUSION: This international benchmark trial has highlighted the differences in worldwide treatment of locally advanced and LRRC. Standardized care should improve outcomes for these patients.
ANTECEDENTES: La extensión del tumor más allá del plano del meso-rrecto (ymrT4) ocurre en el 5-10% de los pacientes con cáncer de recto y el 10% de los pacientes desarrollan recidiva local del cáncer de recto (locally recurrent rectal cáncer, LRRC) después de una cirugía primaria. Existe una variación global en la prestación de la asistencia sanitaria para esta pato-logía. MÉTODOS: Se realizó un ensayo de referencia internacional sobre el manejo de ymrT4 y LRRC en Francia y Australia entre 2015 y 2017. La heterogeneidad en el manejo y la toma de decisiones quirúrgicas se analizaron mediante la comparación de las tasas de resección quirúrgica, la lectura a ciegas de la resonancia magnética (RM) pélvica entre países, la evaluación de la calidad de vida y las evaluaciones cualitativas. RESULTADOS: De 154 pacientes (97 en Francia versus 57 en Australia), el 32% tenía ymrT4 y el 68% tenía cáncer de recto con recidiva local. Las tasas de resección quirúrgica fueron del 87,6% versus 77,8% (P = 0,112). La tasa de concordancia en la decisión quirúrgica fue baja (coeficiente kappa = 0,314) con una tasa más baja de exenteración pélvica en Francia, tanto en la práctica clínica (46% versus 85%; P < 0,0001) como en condiciones teóricas (40% versus 88%; P = 0,002). La tasa de resección R0 fue menor en Francia para la LRRC (51% versus 86%, P = 0,007) pero no para el ymrT4 (81% versus 100%, P = 0,139). Las tasas de morbilidad fueron similares. Los pacientes que se sometieron a procedimientos no exenterativos tuvieron una subescala de funcionamiento mental más alta a los 12 meses (P = 0,04) y un nivel de angustia más bajo a los 6 meses (P = 0,04). El análisis cualitativo destacó 5 categorías de factores psicosociales que afectaron a la decisión del tratamiento: paciente, estrategia, especialista, organización y cultura. CONCLUSIÓN: Este ensayo de referencia internacional destaca las diferencias en el tratamiento mundial del cáncer de recto localmente avanzado y de la LRR. La aten-ción estandarizada debería mejorar los resultados para estos pacientes.
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Benchmarking , Toma de Decisiones Clínicas/métodos , Disparidades en Atención de Salud/estadística & datos numéricos , Pautas de la Práctica en Medicina/estadística & datos numéricos , Neoplasias del Recto/diagnóstico por imagen , Neoplasias del Recto/cirugía , Adulto , Anciano , Australia , Femenino , Francia , Disparidades en Atención de Salud/normas , Humanos , Imagen por Resonancia Magnética/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/diagnóstico por imagen , Recurrencia Local de Neoplasia/psicología , Recurrencia Local de Neoplasia/cirugía , Estadificación de Neoplasias , Pautas de la Práctica en Medicina/normas , Proctectomía/estadística & datos numéricos , Estudios Prospectivos , Investigación Cualitativa , Calidad de Vida , Neoplasias del Recto/patología , Neoplasias del Recto/psicologíaRESUMEN
BACKGROUND: Laser fistulectomy is a minimally invasive, sphincter-sparing procedure for treatment of anal fistula. In several studies, this method has been shown to be safe and effective, with reported success rates ranging from 40 to 88%. We hypothesized that with longer follow-up, these rates would decrease. METHODS: A retrospective case analysis assessing the effectiveness of laser fistulectomy in curing fistula-in-ano tracts within a cohort of patients at a single academic institution was conducted. All patients having laser ablation between March 2016 and July 2018 were analyzed. Cure of the fistula was determined by history and postoperative physical exam, and was defined as complete closure of fistula tract with resolution of symptoms. Secondary symptoms of fecal incontinence, infection, and pain were evaluated. RESULTS: Eighteen patients (10 males, mean age 41 ± 13 years) were analyzed. Transphincteric fistula was the most common type (67%, N = 12). The mean number of previous fistula procedures was 1.33 ± 1.64. There was a 22% (N = 4) success rate at an average postoperative follow-up period of 29 ± 8 months (range 18-46 months). Of those who failed, 64% (N = 9) had a subsequent fistula procedure. There were no cases of fecal incontinence, but 3 cases (17%) of postoperative infection were reported and 8 patients (44%) had a subjective increase in pain at first follow-up appointment. CONCLUSIONS: Our data showed a much higher failure rate of laser fistulectomy compared to those reported in the literature. However, the small sample size, a large amount of heterogeneity in our patient population with a mixture of fistula types present, and various laser techniques applied decreased the power of this study.
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Incontinencia Fecal , Fístula Rectal , Adulto , Canal Anal/cirugía , Estudios de Cohortes , Incontinencia Fecal/etiología , Humanos , Rayos Láser , Masculino , Persona de Mediana Edad , Tratamientos Conservadores del Órgano , Fístula Rectal/cirugía , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
PURPOSE: This study aimed to determine the outcome for patients who had undergone perineal hernia repair, via a perineal approach, using a biological mesh post-abdominoperineal excision (APE) for anorectal cancer. METHOD: All consecutive patients having undergone perineal hernia repair involving an extracellular matrix of porcine small intestinal submucosa at our hospital between 2015 and 2018 were included. Follow-up clinical examinations and computed tomography scans were performed. RESULTS: Six patients were treated surgically for symptomatic perineal hernia after a median of 31 months from APE. The median follow-up after hernia repair was 11 months (interquartile range [IQR], 6-35 months). Three patients (50%) developed a recurrent perineal hernia after a median interval of 6 months. CONCLUSION: Perineal hernia repair using a biological mesh resulted in a high recurrence rate in patients who had undergone APE for anorectal cancer.
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Neoplasias del Ano , Proctectomía , Neoplasias del Recto , Animales , Hernia/etiología , Humanos , Recurrencia Local de Neoplasia , Perineo/cirugía , Neoplasias del Recto/cirugía , Mallas Quirúrgicas , PorcinosRESUMEN
BACKGROUND: NETSARC (netsarc.org) is a network of 26 sarcoma reference centers with specialized multidisciplinary tumor boards (MDTB) aiming to improve the outcome of sarcoma patients. Since 2010, presentation to an MDTB and expert pathological review are mandatory for sarcoma patients nationwide. In the present work, the impact of surgery in a reference center on the survival of sarcoma patients investigated using this national NETSARC registry. PATIENTS AND METHODS: Patients' characteristics and follow-up are prospectively collected and data monitored. Descriptive, uni- and multivariate analysis of prognostic factors were conducted in the entire series (N = 35 784) and in the subgroup of incident patient population (N = 29 497). RESULTS: Among the 35 784 patients, 155 different histological subtypes were reported. 4310 (11.6%) patients were metastatic at diagnosis. Previous cancer, previous radiotherapy, neurofibromatosis type 1 (NF1), and Li-Fraumeni syndrome were reported in 12.5%, 3.6%, 0.7%, and 0.1% of patients respectively. Among the 29 497 incident patients, 25 851 (87.6%) patients had surgical removal of the sarcoma, including 9949 (33.7%) operated in a NETSARC center. Location, grade, age, size, depth, histotypes, gender, NF1, and surgery outside a NETSARC center all correlated to overall survival (OS), local relapse free survival (LRFS), and event-free survival (EFS) in the incident patient population. NF1 history was one of the strongest adverse prognostic factors for LRFS, EFS, and OS. Presentation to an MDTB was associated with an improved LRFS and EFS, but was an adverse prognostic factor for OS if surgery was not carried out in a reference center. In multivariate analysis, surgery in a NETSARC center was positively correlated with LRFS, EFS, and OS [P < 0.001 for all, with a hazard ratio of 0.681 (95% CI 0.618-0.749) for OS]. CONCLUSION: This nationwide registry of sarcoma patients shows that surgical treatment in a reference center reduces the risk of relapse and death.
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Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/cirugía , Sarcoma/mortalidad , Sarcoma/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Francia/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Pronóstico , Estudios Prospectivos , Derivación y Consulta/estadística & datos numéricos , Sistema de Registros , Sarcoma/patología , Procedimientos Quirúrgicos Operativos/normas , Procedimientos Quirúrgicos Operativos/estadística & datos numéricos , Tasa de Supervivencia , Adulto JovenRESUMEN
AIM: To assess shoulder pain and disability in patients undergoing corticosteroid injection into the subacromial-subdeltoid (SA-SD) bursa under ultrasound guidance, evaluating both short and long-term outcomes. MATERIALS AND METHODS: In this prospective, longitudinal, analytical study 376 patients referred for SA-SD bursa injection during a 6 month period were asked to complete a questionnaire assessing shoulder pain and disability in the form of the Shoulder Pain and Disability Index (SPADI). Patients were reassessed at 6 weeks and 12 months post-injection. Data were collated and analysed based on the diagnosis made at ultrasound. RESULTS: Almost two-thirds (63.6%) of patients irrespective of the underlying diagnosis showed improvement in pain and disability 6 weeks after injection, but this figure decreased significantly after 12 months to 27.3%. There was no significant difference in outcome between patients with a rotator cuff tendon tear and without a tear at 6 weeks; however, there was a difference between these two groups at 12 months with significantly fewer patients with a tear receiving benefit. CONCLUSION: The pattern of good short-term, but poorer long-term outcomes from SA-SD bursa injection is in line with previous studies; however, this study provides additional information on the effect of the underlying diagnosis on the potential outcome, specifically the presence or absence of a rotator cuff tendon tear.
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Corticoesteroides/administración & dosificación , Lesiones del Manguito de los Rotadores/tratamiento farmacológico , Dolor de Hombro/tratamiento farmacológico , Ultrasonografía Intervencional , Adulto , Anciano , Anciano de 80 o más Años , Bolsa Sinovial/diagnóstico por imagen , Evaluación de la Discapacidad , Femenino , Humanos , Inyecciones Intraarticulares , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Estudios Prospectivos , Lesiones del Manguito de los Rotadores/diagnóstico por imagen , Dolor de Hombro/diagnóstico por imagen , Resultado del TratamientoRESUMEN
OBJECTIVES: To determine if quantitative and qualitative shear wave elastography have roles in evaluating musculoskeletal masses. METHODS: 105 consecutive patients, prospectively referred for biopsy within a specialist sarcoma centre, underwent B-mode, quantitative (m/s) and qualitative (colour map) shear wave elastography. Reference was histology from subsequent biopsy or excision where possible. Statistical modelling was performed to test elastography data and/or B-mode imaging in predicting malignancy. RESULTS: Of 105 masses, 39 were malignant and 6 had no histology but benign characteristics at 12 months. Radiologist agreement for B-mode and elastography was moderate to excellent Kw 0.52-0.64; PABAKw 0.85-0.90). B-Mode imaging had 78.8% specificity, 76.9% sensitivity for malignancy. Quantitatively, adjusting for age, B-mode and lesion volume there was no statistically significant association between longitudinal velocity and malignancy (OR [95% CI] 0.40[0.10, 1.60], p=0.193), but some evidence that higher transverse velocity was associated with decreased odds of malignancy (0.28[0.06, 1.28], p=0.101). Qualitatively malignant masses tended to be towards the blue spectrum (lower velocities); 39.5% (17/43) of predominantly blue masses were malignant, compared to 14.3% (1/7) of red lesions. CONCLUSIONS: Quantitatively and qualitatively there is no statistically significant association between shear wave velocity and malignancy. There is no clear additional role to B-mode imaging currently. KEY POINTS: ⢠Correlation between shear wave velocity and soft tissue malignancy was statistically insignificant ⢠B-mode ultrasound is 76.9 % sensitive and 78.8 % specific ⢠Statistical models show elastography does not significantly add to lesion assessment.
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Diagnóstico por Imagen de Elasticidad/métodos , Sarcoma/diagnóstico por imagen , Neoplasias de los Tejidos Blandos/diagnóstico por imagen , Ultrasonografía Doppler en Color/métodos , Adulto , Anciano , Anciano de 80 o más Años , Biopsia , Femenino , Tumor Glómico/diagnóstico por imagen , Humanos , Liposarcoma/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Peso Molecular , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Ultrasonografía , Adulto JovenRESUMEN
BACKGROUND: Robotic ventral mesh rectopexy (RVMR) is an appealing approach for the treatment of rectal prolapse and other conditions. The aim of this study was to evaluate the outcomes of RVMR for rectal prolapse. METHODS: We performed a retrospective chart review for patients who underwent RVMR for rectal prolapse at our institution between July 2012 and May 2016. Any patient who underwent RVMR during this time frame was included in our analysis. Any cases involving colorectal resection or other rectopexy techniques were excluded. RESULTS: Of the 24 patients who underwent RVMR, 95.8% of patients were female. Median age was 67.5 years old (IQR 51.5-73.3), and 79.2% of patients were American Society of Anesthesiologists class III or IV. Median operative time was 191 min (IQR 164.3-242.5), and median length of stay was 3 days (IQR 2-3). There were no conversions, RVMR-related complications or mortality. Patients were followed for a median of 3.8 (IQR 1.2-15.9) months. Full-thickness recurrence occurred in 3 (12.4%) patients. Rates of fecal incontinence improved after surgery (62.5 vs. 41.5%, respectively) as did constipation (45.8 vs. 33.3%, respectively). No patients reported worsening symptoms postoperatively. Only one (4.2%) patient reported de novo constipation postoperatively. CONCLUSIONS: RVMR is a feasible, safe and effective option for the treatment of rectal prolapse, with low short-term morbidity and mortality. Multicenter and long-term studies are needed to better assess the benefits of this procedure.
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Prolapso Rectal/cirugía , Procedimientos Quirúrgicos Robotizados/métodos , Mallas Quirúrgicas , Anciano , Estreñimiento/etiología , Incontinencia Fecal/etiología , Femenino , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Tempo Operativo , Prolapso Rectal/complicaciones , Recurrencia , Estudios Retrospectivos , Resultado del TratamientoAsunto(s)
Adenocarcinoma/cirugía , Canal Anal/cirugía , Neoplasias del Recto/cirugía , Adenocarcinoma/mortalidad , Adenocarcinoma/radioterapia , Supervivencia sin Enfermedad , Humanos , Estimación de Kaplan-Meier , Márgenes de Escisión , Terapia Neoadyuvante/métodos , Neoplasias del Recto/mortalidad , Neoplasias del Recto/radioterapia , Análisis de SupervivenciaRESUMEN
During recent decades, hydrophilic interaction liquid chromatography (HILIC) ahs been introduced to fractionate or purify especially polar solutes such as peptides and proteins while reversed-phase liquid chromatography (RPLC) is also a common strategy. RPLC is also a common dimension in multidimensional chromatography. In this study, the potential of HILIC vs RPLC chromatography was compared for proteome mapping of human peripheral blood mononuclear cell extract. In HILIC a silica-based stationary phase and for RPLC a C18 column were applied. Then separated proteins were eluted to an ion trap mass spectrometry system. Our results showed that the HILIC leads to more proteins being identified in comparison to RPLC. Among the total 181 identified proteins, 56 and 38 proteins were fractionated specifically by HILIC and RPLC, respectively. In order to demonstrate this, the physicochemical properties of identified proteins such as polarity and hydrophobicity were considered. This analysis indicated that polarity may play a major role in the HILIC separation of proteins vs RPLC. Using gene ontology enrichment analysis, it was also observed that differences in physicochemical properties conform to the cellular compartment and biological features. Finally, this study highlighted the potential of HILIC and the great orthogonality of RPLC in gel-free proteomic studies. Copyright © 2015 John Wiley & Sons, Ltd.
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Cromatografía de Fase Inversa/métodos , Proteómica , Humanos , Interacciones Hidrofóbicas e HidrofílicasRESUMEN
Memory impairment is a common disorder in diabetes mellitus which is associated with hippocampal neuronal apoptosis. The present study was conducted to examine the effect of one-week intraperitoneal (ip), administration of aminoguanidine (AG) on passive avoidance learning (PAL) and Bcl-2 family gene expression in the hippocampus of rats. Sixty male rats were divided into ten groups: non-diabetic/diabetic animals with/without AG (50, 100, 200 and 400 mg/kg, ip) treatment for one week. PAL and Bcl-2 family genes were examined. AG (100 and 200 mg/kg) improved both memory and Bax, Bak, Bcl-2 and Bcl-xl deficiency significantly in diabetic rats. AG treatment also ameliorated the diabetes-induced changes in (Bcl-2+Bcl-xl)/(Bak+Bax) ratios considerably. These results propose that one-week ip administration of AG may recover the deficit cognition in diabetic rats via enhancing (Bcl-2+Bcl-xl)/(Bak+Bax) proportions (Tab. 2, Fig. 4, Ref. 55).
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Apoptosis/efectos de los fármacos , Reacción de Prevención/efectos de los fármacos , Guanidinas/farmacología , Memoria/efectos de los fármacos , Proteína X Asociada a bcl-2/biosíntesis , Proteína bcl-X/biosíntesis , Animales , Proteínas Reguladoras de la Apoptosis/biosíntesis , Reacción de Prevención/fisiología , Diabetes Mellitus Experimental/metabolismo , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Inyecciones Intraperitoneales , Masculino , Memoria/fisiología , Proteínas Proto-Oncogénicas c-bcl-2/biosíntesis , Distribución Aleatoria , Ratas , Ratas WistarRESUMEN
The endocannabinoid system serves as a retrograde negative feedback mechanism. It is thought to control neuronal activity in an epileptic neuronal network. The purpose of this study was to evaluate the impact of the endocannabinoid and endovanilloid systems on both epileptogenesis and ictogenesis. Therefore, we modulated the endocannabinoid and endovanilloid systems genetically and pharmacologically, and analyzed the subsequent impact on seizure progression in the kindling model of temporal lobe epilepsy in mice. In addition, the impact of seizures on associated cellular alterations was evaluated. Our principal results revealed that the endocannabinoid system affects seizure and afterdischarge duration dependent on the neuronal subpopulation being modulated. Genetic deletion of CB1-receptors (CB1Rs) from principal neurons of the forebrain and pharmacological antagonism with rimonabant (5 mg/kg) caused longer seizure duration. Deletion of CB1R from GABAergic forebrain neurons resulted in the opposite effect. Along with these findings, the CB1R density was elevated in animals with repetitively induced seizures. However, neither genetic nor pharmacological interventions had any impact on the development of generalized seizures. Other than CB1, genetic deletion or pharmacological blockade with SB366791 (1 mg/kg) of transient receptor potential vanilloid receptor 1 (TRPV1) had no effect on the duration of behavioral or electrographic seizure activity in the kindling model. In conclusion, we demonstrate that endocannabinoid, but not endovanilloid, signaling affects termination of seizure activity, without influencing seizure severity over time. These effects are dependent on the neuronal subpopulation. Thus, the data argue that the endocannabinoid system plays an active role in seizure termination but does not regulate epileptogenesis.
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Epilepsia/genética , Epilepsia/patología , Excitación Neurológica/genética , Neuronas/metabolismo , Prosencéfalo/patología , Receptor Cannabinoide CB1/deficiencia , Anilidas/farmacología , Animales , Bromodesoxiuridina , Proteína Quinasa Tipo 1 Dependiente de Calcio Calmodulina/genética , Proteína Quinasa Tipo 1 Dependiente de Calcio Calmodulina/metabolismo , Antagonistas de Receptores de Cannabinoides/efectos adversos , Cinamatos/farmacología , Modelos Animales de Enfermedad , Regulación de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica/genética , Masculino , Ratones , Ratones Noqueados , Neurogénesis/efectos de los fármacos , Neurogénesis/genética , Neuronas/efectos de los fármacos , Piperidinas/efectos adversos , Pirazoles/efectos adversos , Rimonabant , Canales Catiónicos TRPV/genética , Canales Catiónicos TRPV/metabolismo , Ácido gamma-Aminobutírico/metabolismoRESUMEN
Bisphosphonates are important therapeutic agents in bone-related diseases and exhibit complex H-bonding networks. To assess the role of H-bonds in biophosphonate stability, a full conformational search was performed for methylenebisphosphonate (MBP) and 1-hydroxyethylidene-1,1-diphosphonate (HEDP) using the MP2 method in conjunction with the continuum solvation model. The most stable structures and their equilibrium populations were analyzed at two protonation states via assignment of H-bonding motifs to each conformer. Geometrical and topological approaches for the identification and characterization of H-bonds were compared with each other, and some of the important correlations between H-bond features were described over the entire conformational space of a hydroxy-bisphosphonate moiety. The topologically derived H-bond energy obtained from the local density of potential energy at bond critical points shows consistent correlations with other measures such as H-bond frequency shift. An inverse power form without an intercept predicts topological H-bond energies from hydrogen-acceptor distances with an RMS error of less than 1 kcal mol(-1). The consistency of this measure was further checked by building a model that reasonably reproduces the relative stabilities of different conformers from their hydrogen-acceptor distances. In all systems, the predictions of this model are improved by the consideration of weak H-bonds that have no bond critical point.
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Difosfonatos/química , Enlace de Hidrógeno , Modelos Moleculares , Conformación Molecular , Teoría Cuántica , TermodinámicaRESUMEN
AIM: In the present study, the role of ethanol extract of root of Taraxacum Syriacum Boiss (TSBE) against hepatotoxicity caused by acetaminophen (APAP) was studied. METHODS: The chemical composition of roots of Taraxacum Syriacum Boiss was analyzed by SPME-GC/MS method. Hepatocellular injuries induced by acetaminophen (APAP) were assessed by liver histology, serum aminotransferase activities, antioxidant enzymes activity and lipid peroxidation in liver tissue. RESULTS: TSBE was observed to exhibit hepatoprotective effect as demonstrated by significant decrease in serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), and alkaline phosphatase (ALP) concentration, and by preventing liver histopathologic changes in rats with APAP hepatotoxicity. Administration of APAP, significantly increased, lactate dehydrogenase (LDH) and catalase (CAT) activity in liver tissue and pretreatment with TSBE returned these parameters to control group, moreover TSBE reduces APAP-induced hepatic Glutathione (GSH) depletion. Carvacrol (6.7 %) was the main polyphenolic compound of plant sample. Our results demonstrated hepatoprotective activity of TSBE in rat in vivo. CONCLUSIONS: We believe that the mechanism by which the extract was able to protect the liver from the oxidative stress generated by APAP is due to its antioxidant activity. These phenolic compounds of the extract act as antioxidants and free radical scavengers and reduce or inhibit the oxidative stress induced by APAP administration (Tab. 3, Fig. 3, Ref. 39).
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Acetaminofén/toxicidad , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Extractos Vegetales/química , Extractos Vegetales/farmacología , Sustancias Protectoras/química , Sustancias Protectoras/farmacología , Taraxacum , Alanina Transaminasa/sangre , Fosfatasa Alcalina/sangre , Animales , Antioxidantes/farmacología , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Etanol , Depuradores de Radicales Libres/farmacología , Hepatocitos/efectos de los fármacos , Peroxidación de Lípido/efectos de los fármacos , Masculino , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas WistarRESUMEN
Pseudoporphyria refers to a rare bullous dermatosis characterized by the clinical and histological features of porfiria cutanea tarda without abnormalities in porphyrin metabolism. The pathogenesis is heterogeneous and several exogenous factors may promote the bullous lesion formation, including medications, end stage renal disease, dialysis and tanning beds. Regarding treatment of this condition, in literature different therapy have been reported, such as glutathione and his precursor N-acetylcysteine, which presents anti-oxidant properties; however even more toxic drugs, such as chloroquine, are used. Moreover, in patients with drug-induced PP discontinuation of the offending agent, if possible, is a crucial aspect of the clinical management. We report two cases of dialysis patients presenting blisters on extremities, which healed with the avoidance of UV exposure and oral Vitamin D supplementation. Interestingly Vitamin D despite the lack of antioxidant properties led to a completely resolution of PP in both our patients within 30 days. A possible explanation of this finding is that Vitamin D, playing a key role in the regulation of serum Ca2+, can modulated cadherin-cadherin interactions and led to healing of pseudoporphyria bullous lesions. Finally we highlight the prominent role of UV-exposure in PP elicitation thus a good photoprotection is essential for all patients with pseudoporphyria.
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Trastornos por Fotosensibilidad/tratamiento farmacológico , Diálisis Renal/efectos adversos , Enfermedades Cutáneas Vesiculoampollosas/tratamiento farmacológico , Luz Solar/efectos adversos , Rayos Ultravioleta/efectos adversos , Deficiencia de Vitamina D/complicaciones , Vitamina D/uso terapéutico , Anciano , Calcio/fisiología , Técnicas Cosméticas/efectos adversos , Cadherinas Desmosómicas/fisiología , Diagnóstico Diferencial , Femenino , Humanos , Uniones Intercelulares , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/terapia , Persona de Mediana Edad , Nefroesclerosis/complicaciones , Diálisis Peritoneal/efectos adversos , Trastornos por Fotosensibilidad/diagnóstico , Trastornos por Fotosensibilidad/etiología , Porfiria Cutánea Tardía/diagnóstico , Porfirinas/análisis , Enfermedades Cutáneas Vesiculoampollosas/diagnóstico , Enfermedades Cutáneas Vesiculoampollosas/etiología , Vitamina D/fisiología , Deficiencia de Vitamina D/tratamiento farmacológicoRESUMEN
BACKGROUND: Retroperitoneal sarcomas (RPS) are heterogeneous. No previous study has investigated the impact of specialized surgery, evaluated locoregional relapse (LRR), abdominal sarcomatosis and distant metastatic relapse as separate events, or considered histological subtypes separately. This study addresses these specific points in a homogeneous cohort of patients with completely resected primary RPS. PATIENTS AND METHODS: We conducted a retrospective analysis of adult patients diagnosed with a RPS between 1 January 1988 and 31 December 2008 and eventually referred to one of 12 centers of the French Sarcoma Group. All cases were centrally reviewed by an expert pathologist. RESULTS: Five hundred eighty-six patients were included. Median follow-up was 6.5 years [95% confidence interval (CI) 5.9-7.1]. Five hundred thirty-seven patients had localized disease and 389 patients (76%) had macroscopically complete resection of the tumor. In this latter group, the 5-year LRR-free survival rate was 46% [41-52] and the 5-year overall survival (OS) rate was 66% [61-71]. In multivariate analysis, gender, adjacent organ involvement, specialization of the surgeon, piecemeal resection and perioperative radiotherapy were independently associated with LRR. Specialization of the surgeon and piecemeal resection were independently associated with abdominal sarcomatosis whereas histology and adjacent organ involvement were independently associated with distant metastasis. Age, gender, grade, adjacent organ involvement and piecemeal resection were significantly associated with OS. Prognostic factors for LRR and OS were analyzed in well-differentiated and dedifferentiated liposarcomas and leiomyosarcomas. Grade 3 was an independent prognostic factor for OS of dedifferentiated liposarcomas. CONCLUSION: This study underlines the crucial role of pretherapeutic assessment and meticulous histological examination of RPS as well as the need to consider histological subtypes separately. Surgery in a specialized center and avoidance of piecemeal resection stand out as the two most important prognostic factors for RPS and highlight the importance of treating these patients in specialized centers.