Microbiome-induced Increases and Decreases in Bone Tissue Strength can be Initiated After Skeletal Maturity.

Recent studies in mice have indicated that the gut microbiome can regulate bone tissue strength. However, prior work involved modifications to the gut microbiome in growing animals and it is unclear if the same changes in the microbiome, applied later in life, would change matrix strength. Here we changed the composition of the gut microbiome before and/or after skeletal maturity (16 weeks of age) using oral antibiotics (ampicillin + neomycin). Male and female mice (n=143 total, n=12-17/group/sex) were allocated into five study groups:1) Unaltered, 2) Continuous (dosing 4-24 weeks of age), 3) Delayed (dosing only 16-24 weeks of age), 4) Initial (dosing 4-16 weeks of age, suspended at 16 weeks), and 5) Reconstituted (dosing from 4-16 weeks following by fecal microbiota transplant from Unaltered donors). Animals were euthanized at 24 weeks of age. In males, bone matrix strength in the femur was 25-35% less than expected from geometry in mice from the Continuous (p= 0.001), Delayed (p= 0.005), and Initial (p=0.040) groups as compared to Unaltered. Reconstitution of the gut microbiota, however, led to a bone matrix strength similar to Unaltered animals (p=0.929). In females, microbiome-induced changes in bone matrix strength followed the same trend as males but were not significantly different, demonstrating sex-related differences in the response of bone matrix to the gut microbiota. Minor differences in chemical composition of bone matrix were observed (Raman spectroscopy). Our findings indicate that microbiome-induced impairment of bone matrix in males can be initiated and/or reversed after skeletal maturity. The portion of the femoral cortical bone formed after skeletal maturity (16 weeks) is small; however, this suggests that microbiome-induced changes in bone matrix occur without osteoblast/osteoclast turnover using an, as of yet unidentified mechanism. These findings add to evidence that the mechanical properties of bone matrix can be altered in the adult skeleton.

A multi-institutional analysis of intraoperative radiotherapy for early breast cancer: Does age matter?

BACKGROUND: Single-session intraoperative radiation therapy (IORT) minimizes treatment demands associated with traditional whole breast radiation therapy (WBRT) but outcomes on local disease control and morbidity among the elderly is limited. METHODS: A multi-institutional retrospective registry was established from 19 centers utilizing IORT from 2007 to 2013. Patient, tumor, and treatment variables were analyzed for ages <70 and ≥70. RESULTS: We evaluated 686 patients (<70 = 424; ≥70 = 262) who were margin and lymph node negative. Patients <70 were more likely to have longer operative time, oncoplastic closure, higher rates of IORT used as planned boost, and receive chemotherapy and post-operative WBRT. Wound complication rates were low and not significantly different between age groups. Median follow-up was 1.06 (range 0.51-1.9) years for < 70 and 1.01 (range 0.5-1.68) years for ≥ 70. There were 5 (0.73%) breast recurrences (4 in <70 and 1 ≥ 70, p = 0.65) and no axillary recurrences during follow-up. CONCLUSIONS: IORT was associated with a low rate of wound complication and local recurrence on short-term follow-up in this cohort.

Successful maintenance on sulphonylurea therapy and low diabetes complication rates in a HNF1A-MODY cohort.

AIMS: HNF1A gene mutations are the most common cause of maturity-onset diabetes of the young (MODY) in the UK. Persons with HNF1A-MODY display sensitivity to sulphonylurea therapy; however, the long-term efficacy is not established. There is limited literature as to the prevalence of micro- and macrovascular complications in this unique cohort. The aim of this study was to determine the natural progression and clinical management of HNF1A-MODY diabetes in a dedicated MODY clinic. METHODS: Sixty patients with HNF1A-MODY and a cohort of 60 BMI-, age-, ethnicity- and diabetes duration-matched patients with Type 1 diabetes mellitus participated in the study. All patients were phenotyped in detail. Clinical follow-up of the HNF1A-MODY cohort occurred on a bi-annual basis. RESULTS: Following a genetic diagnosis of MODY, the majority of the cohort treated with sulphonylurea therapy remained insulin independent at 84-month follow-up (80%). The HbA1c in the HNF1A-MODY group treated with sulphonylurea therapy alone improved significantly over the study period [from 49 (44-63) mmol/mol, 6.6 (6.2-7.9)% to 41 (31-50) mmol/mol, 5.9 (5-6.7)%; P = 0.003]. The rate of retinopathy was significantly lower than that noted in the Type 1 diabetes mellitus group (13.6 vs. 50%; P = 0.0001).There was also a lower rate of microalbuminuria and cardiovascular disease in the HNF1A-MODY group compared with the Type 1 diabetes mellitus group. CONCLUSIONS: This study demonstrates that the majority of patients with HNF1A-MODY can be maintained successfully on sulphonylurea therapy with good glycaemic control. We note a significantly lower rate of micro- and macrovascular complications than reported previously. The use of appropriate therapy at early stages of the disorder may decrease the incidence of complications.

Segmentation editing improves efficiency while reducing inter-expert variation and maintaining accuracy for normal brain tissues in the presence of space-occupying lesions.

Image segmentation has become a vital and often rate-limiting step in modern radiotherapy treatment planning. In recent years, the pace and scope of algorithm development, and even introduction into the clinic, have far exceeded evaluative studies. In this work we build upon our previous evaluation of a registration driven segmentation algorithm in the context of 8 expert raters and 20 patients who underwent radiotherapy for large space-occupying tumours in the brain. In this work we tested four hypotheses concerning the impact of manual segmentation editing in a randomized single-blinded study. We tested these hypotheses on the normal structures of the brainstem, optic chiasm, eyes and optic nerves using the Dice similarity coefficient, volume, and signed Euclidean distance error to evaluate the impact of editing on inter-rater variance and accuracy. Accuracy analyses relied on two simulated ground truth estimation methods: simultaneous truth and performance level estimation and a novel implementation of probability maps. The experts were presented with automatic, their own, and their peers' segmentations from our previous study to edit. We found, independent of source, editing reduced inter-rater variance while maintaining or improving accuracy and improving efficiency with at least 60% reduction in contouring time. In areas where raters performed poorly contouring from scratch, editing of the automatic segmentations reduced the prevalence of total anatomical miss from approximately 16% to 8% of the total slices contained within the ground truth estimations. These findings suggest that contour editing could be useful for consensus building such as in developing delineation standards, and that both automated methods and even perhaps less sophisticated atlases could improve efficiency, inter-rater variance, and accuracy.

SU-E-I-76: Optimizing Imaging Parameters for a Novel Radiographic Imaging System for the Detection of Corrosion in Aluminum Aircraft Structures.

PURPOSE: A laboratory-based phase-contrast radiography/tomosynthesis imaging system previously (Med. Phys. Vol. 38, 2353 May 2011) for improved detection of low-contrast soft-tissue masses was used to evaluate the sensitivity for detecting the presence of thin layers of corrosion on aluminum aircraft structures. METHODS: The evaluation utilized a test object of aluminum (2.5 inch × 2.5 inch × 1/8 inch) on which different geometric patterns of 0.0038 inch thick anodized aluminum oxide was deposited. A circular area of radius 1 inch centered on the phantom's midpoint was milled to an approximate thickness of 0.022 inches. The x-ray source used for this investigation was a dual focal spot, tungsten anode x-ray tube. The focal used during the investigation has a nominal size of 0.010 mm. The active area of the imager is 17.1 cm × 23.9 cm (2016 × 2816 pixels) with a pixel pitch of 0.085 mm. X-ray tube voltages ranged from 20-40 kVp and source- to-object and object-to-image distances were varied from 20-100 cm. Performance of the phase-contrast mode was compared to conventional absorption-based radiography using contrast ratio and contrast-to-noise ratios (C/N). Phase-contrast performance was based on edge-enhancement index (EEI) and the edge-enhancement-to-noise (EE/N) ratio. RESULTS: for absorption-based radiography, the best C/N ratio was observed at the lowest kVp value (20 kVp). The optimum sampling angle for tomosynthesis was +/- 8 degrees. CONCLUSIONS: Comparing C/N to EE/N demonstrated the phase-contrast techniques improve the conspicuity of the oxide layer edges. This work provides the optimal parameters that a radiographic imaging system would need to differentiate the two different compounds of aluminum. Subcontractee from Positron Systems Inc. (Boise, Idaho) through United States Air Force grant (AF083-225).

Comparison of manual and automatic segmentation methods for brain structures in the presence of space-occupying lesions: a multi-expert study.

The purpose of this work was to characterize expert variation in segmentation of intracranial structures pertinent to radiation therapy, and to assess a registration-driven atlas-based segmentation algorithm in that context. Eight experts were recruited to segment the brainstem, optic chiasm, optic nerves, and eyes, of 20 patients who underwent therapy for large space-occupying tumors. Performance variability was assessed through three geometric measures: volume, Dice similarity coefficient, and Euclidean distance. In addition, two simulated ground truth segmentations were calculated via the simultaneous truth and performance level estimation algorithm and a novel application of probability maps. The experts and automatic system were found to generate structures of similar volume, though the experts exhibited higher variation with respect to tubular structures. No difference was found between the mean Dice similarity coefficient (DSC) of the automatic and expert delineations as a group at a 5% significance level over all cases and organs. The larger structures of the brainstem and eyes exhibited mean DSC of approximately 0.8-0.9, whereas the tubular chiasm and nerves were lower, approximately 0.4-0.5. Similarly low DSCs have been reported previously without the context of several experts and patient volumes. This study, however, provides evidence that experts are similarly challenged. The average maximum distances (maximum inside, maximum outside) from a simulated ground truth ranged from (-4.3, +5.4) mm for the automatic system to (-3.9, +7.5) mm for the experts considered as a group. Over all the structures in a rank of true positive rates at a 2 mm threshold from the simulated ground truth, the automatic system ranked second of the nine raters. This work underscores the need for large scale studies utilizing statistically robust numbers of patients and experts in evaluating quality of automatic algorithms.

Exploring feature-based approaches in PET images for predicting cancer treatment outcomes.

Accumulating evidence suggests that characteristics of pre-treatment FDG-PET could be used as prognostic factors to predict outcomes in different cancer sites. Current risk analyses are limited to visual assessment or direct uptake value measurements. We are investigating intensity-volume histogram metrics and shape and texture features extracted from PET images to predict patient's response to treatment. These approaches were demonstrated using datasets from cervix and head and neck cancers, where AUC of 0.76 and 1.0 were achieved, respectively. The preliminary results suggest that the proposed approaches could potentially provide better tools and discriminant power for utilizing functional imaging in clinical prognosis.

Initial investigation OF 222Rn in the Tbilisi urban environment.

Georgia has geological formations with high uranium content, and several buildings are built with local materials. This can create potentially high radon exposures. Consequently, studies to mitigate these exposures have been started. This study presents a preliminary investigation of radon in Tbilisi, the capital of Georgia. An independent radiological monitoring program in Georgia has been initiated by the Radiocarbon and Low-Level Counting Section of I. Javakhishvili Tbilisi State University with the cooperation of the Environmental Monitoring Laboratory of the Physics/Health Physics Department at Idaho State University. At this initial stage the E-PERM systems and GammaTRACER were used for the measurement of gamma exposure and radon concentrations in air and water. Measurements in Sololaki, a densely populated historic district of Tbilisi, revealed indoor radon (222Rn) concentrations of 1.5-2.5 times more than the U.S. Environmental Protection Agency action level of 148 Bq m(-3) (4 pCi L(-1)). Moreover, radon-in-air concentrations of 440 Bq m(-3) and 3,500 Bq m(-3) were observed at surface borehole openings within the residential district. Measurements of water from various tap water supplies displayed radon concentrations of 3-5 Bq L(-1) while radon concentrations in water from the hydrogeological and thermal water boreholes were 5-19 Bq L(-1). In addition, the background gamma absorbed dose rate in air ranged of 70-115 nGy h(-1) at the radon test locations throughout the Tbilisi urban environment.

Abordaje laparoscópico del cáncer de recto / Laparoscópico boarding of the rectum cancer

Antecedentes: Las controversias acerca del abordaje laparoscópico del cáncer de recto aún no han sido delucidadas. Objetivo: Evaluar la factibilidad, seguridad, recurrencia y supervivencia de la resección rectal laparoscópica. Material y métodos: Un total de 230 intervenciones colorrectales laparoscópicas se llevaron a cabo entre 1993 y 2004, 38 de ellas por cáncer de recto (inferior 6, medio 14 y superior 18). Se evalúan los resultados operatorios, morbilidad, recurrencia y la supervivencia global. Resultados: El tiempo operatorio promedio fue de 206 minutos. La altura media de las lesiones fue 9,1 cm. El número promedio de nódulos fue 10. La conversión del 10,5%, las complicaciones intraoperatorias fueron del 16%, la morbilidad inmediata post operatoria del 19%. La recurrencia local 2,6% y la mortalidad del 2,7%. La supervivencia del 78,4% luego de un seguimiento promedio de 42 meses (10-120 meses). Conclusiones: La cirugía laparoscópica rectal es factible y segura. Los resultados oncológicos son similares a los de la cirugía convencional.

Finite element comparison of performance related characteristics of balloon expandable stents.

Cardiovascular stents are commonly made from 316L stainless steel and are deployed within stenosed arterial lesions using balloon expansion. Deployment involves inflating the balloon and plastically deforming the stent until the required diameter is obtained. This plastic deformation induces static stresses in the stent, which will remain for the lifetime of the device. In order to determine these stresses, finite element models of the unit cells of geometrically different, commercially available balloon expandable stents have been created, and deployment and elastic recoil have been simulated. In this work the residual stresses associated with deployment and recoil are compared for the various stent geometries, with a view to establishing appropriate initial stress states for fatigue loading for the stents. The maximum, minimum, and mean stresses induced in the stent due to systolic/diastolic pressure are evaluated, as are performance measures such as radial and longitudinal recoil.

Impacto de la conversión en la cirugía laparoscópica colorrectal / Impact in converted colorectal laparoscopic surgery

Antecedentes: La incidencia de la conversión de cirugía colorrectal laparoscópica a cirugía convencional varía según las series. La evolución postoperatoria de estos pacientes es controvertida. Se ha sugerido que la conversión aumenta la morbi-mortalidad postoperatoria. Objetivo: Analizar el impacto en la morbi-mortalidad postoperatoria de la conversión de la cirugía colorrectal laparoscópica a cirugía convencional. Lugar de aplicación: Servicio de Coloproctología. Hospital Privado de Comunidad. Diseño: Estudio retrospectivo. Registro consecutivo prospectivo de datos. Población: 193 casos operados por laparoscopia por patología colorrectal, electiva. Período: enero de 1993 y noviembre de 2004. Método: Se compararon 3 grupos de pacientes operados por patología colorrectal electiva. Grupo 1: operados por vía laparoscópica, grupo 2: convertidos a cirugía abierta; grupo 3: operados por vía convencional. Resultados: 28 casos convertidos (14,5 por ciento). Edad: 62 años. Sexo masculino: 64 por ciento. Complicaciones inmediatas: 3 casos (10,7 por ciento). Reoperación: 3,5 por ciento (1 caso). Hubo 2 eventos fatales en la serie (mortalidad: 7,1 por ciento). Tiempo operatorio: 209 minutos. Tiempo de internación: 5,2 días. Las complicaciones en el grupo convencional fueron del 5,6 por ciento en 253 casos operados (2002-2004). Hubo 7 casos reoperados (2,76 por ciento) y 1 caso fatal (mortalidad del 0,4 por ciento). Conclusiones: la conversión no afecta la morbi-mortalidad postoperatoria y los costos al ser comparados con laparotomías complejas. La evidencia actual no demuestra un efecto deletéreo de la conversión en cirugía laparoscópica en el cáncer de colon. La conversión en sí misma no debería considerarse como una complicación, aunque es cierto que la evolución postoperatoria en estos pacientes está asociada con resultados dispares, principalmente en morbi-mortalidad

Enfermedad diverticular del colon: tratamiento quirúrgico. Nuestra experiencia / Diverticular disease of the colon: surgical treatment. Our experience

Objetivo: Evaluar retrospectivamente la experiencia en el tratamiento quirúrgico de la enfermedad diverticular del colon durante los últimos años. Lugar: Hospital de comunidad. Material y Métodos: Revisión de 108 historias clínicas de pacientes operados portadores de enfermedad diverticular del colon. Diseño retrospectivo, observacional, transversal. Las variables analizadas fueron las siguientes: Motivo de consulta e indicación quirúrgica, métodos complementarios de diagnóstico en relación al cuadro clínico, tipo de cirugía y morbimortalidad. Resultados: La causa más frecuente de consulta y de indicación quirúrgica fue la sigmoiditis diverticular, de los cuales 41 tenían signos endoscópicos positivos para indicar tratamiento quirúrgico. El 90,7 por ciento de la serie se operaron en forma electiva, mientras que en el 9,3 por ciento se realizó cirugía de urgencia. La morbilidad global fue del 19 por ciento y la mortalidad del 0,9 por ciento. Conclusiones. Coincidimos con la tendencia mundial de realizar resecciones primarias con o sin derivación

Metallothionein crypt-restricted immunopositivity indices (MTCRII) correlate with aberrant crypt foci (ACF) in mouse colon.

Metallothionein (MT) crypt-restricted immunopositivity indices (MTCRII) are colonic crypt stem cell mutation markers that may be induced early and in abundance after mutagen treatment. Metallothionein is the endogenous reporter gene for MTCRII, but is not typically implicated in the classical pathway of colorectal tumorigenesis. Hence, the oncological relevance of MTCRII is unclear. This study tests the hypothesis that MTCRII induced by N-methyl-N-nitrosourea (MNU) and lambda carrageenan (lambdaCgN) associate with aberrant crypt foci (ACF) in mouse colon. Undegraded lambdaCgN and MNU were tested alone and in combination against MTCRII and ACF in Balb/c mice, at 20 weeks after the start of treatment. MTCRII were unaffected by lambdaCgN alone. Combined lambdaCgN/MNU treatments induced greater MTCRII (P < 0.01) as well as greater number (P < 0.001) and crypt multiplicity (P < 0.01) of ACF than MNU alone. MTCRII were approximately 10-fold more numerous than ACF, although linear correlations were observed between these parameters (r = 0.732; P < 0.01). MTCRII are induced by lambdaCgN/MNU interactions in sufficient numbers to provide statistical power from relatively small sample sizes and correlate with ACF formation. MTCRII could thus provide the basis for a novel medium-term murine bioassay relevant to early-stage colorectal tumorigenesis.

Utilidad y factibilidad del colon por enema en forma inmediata a una videocolonoscopía incompleta / Utility and feasibility of the barium enema immediately after an incomplete colonoscopy

Introducción: La videocolonoscopía es el método inicial más apropiado para la evaluación diagnóstica del colon. Existe un índice variable de endoscopías incompletas aún en manos entrenadas. La realización de otro método en otra sesión implica someter al paciente a múltiples preparaciones colónicas, las cuales no son inocuas ni dejan de ser irritativas y molestas. La realización de una Rx. de colon por enema en forma sucesiva el mismo día, es una alternativa válida. Objetivo: Evaluar la factibilidad de la realización de un colon por enema luego de una endoscopía incompleta, analizar sus hallazgos y morbilidad asociada. Diseño: Estudio prospectivo consecutivo. Pacientes: Todos los pacientes con videocolonoscopía incompleta a los que le realizaron un colon por enema en forma inmediata. Métodos: Exclusión: pacientes con mala preparación colónica, falta de recuperación post-anestésica, polipectomías mayores a 1 cm. de diámetro, no aceptación del paciente e indicación de urgencia. Se consideró incompleta la videocolonoscopía cuando no pudo valorar todos los segmentos del colon o no hubiera logrado llegar al ciego. Se evaluaron: nivel anatómico alcanzado, causas de estudio incompleto, hallazgos, morbilidad. Periodo: mayo de 2001 y diciembre de 2003. Lugar: Hospital Privado de Comunidad. Resultados: se realizaron 1546 colonoscopías programadas y ambulatorias; 132 fueron incompletas (8,5 por ciento). Se excluyeron 6 casos (n = 126). Edad: 62 años, sexo femenino: 80 (63,5 por ciento). El colon por enema aportó información en 30 casos (23,8 por ciento). En 23 de los 30 casos el estudio radio lógico aportó nueva información en el colon estudiado (18,3 por ciento), que fueron encontrados en sentido proximal al sitio infranqueable por endoscopía. No se pudo completar el colon por enema en sólo un caso (0,8 por ciento). La sensibilidad, especificidad, valor predictívo negativo y valor predictívo positivo fueron de 91, 99, 95 y 98 por ciento respectivamente. No hubo morbilid...

Proctitis inducida por glutaraldehido / Proctitis induced for glutaraldehyde

Introducción: La incidencia de complicaciones de la colonoscopía es del 0,1 al 3 por ciento y las más frecuentes son la perforación y la hemorragia. Las lesiones producidas por glutaraldehído al 2 por ciento son menos frecuentes y se deben a un efecto tóxico por acción directa sobre la mucosa del colon. Objetivo: analizar la proctitis por este desinfectante y analizar su presentación clínica. Diseño: Análisis retrospectivo. Revisión de la literatura. Pacientes: se registraron todas las colonoscopías (diagnósticas y terapéuticas), realizadas entre enero de 1996 y julio 2004. Métodos: se analizaron las complicaciones. Se realizó una actualización bibliográfica en bases nacionales e informáticas internacionales. Se evaluaron sexo y edad, tipo de endoscopía, sitio afectado, lesiones únicas o múltiples, presentación clínica y metodología diagnóstica, tiempo del diagnóstico, tipo de tratamiento y morbilidad asociada. El proceso de desinfección del instrumental se realizó según las normas establecidas por el servicio de infectología. Resultados: en un total de 4790 colonoscopías, se registraron 5 lesiones (0,1 por ciento) atribuidas al glutaraldehído. Fueron 2 pacientes del sexo masculino y 2 del sexo femenino. Una paciente tuvo dos episodios en dos colonoscopías. La edad promedio fue de 66 años. Todos fueron diagnosticados por la clínica. La presentación consistió en mucorrea, proctorragia leve, pujo y tenesmo. Ningún caso se presentó después de las 48 horas. El diagnóstico presuntivo fue confirmado por rectosigmoideoscopia con biopsia. Histología: rectitis inespecífica. El tratamiento fue sintomático y realizado en forma ambulatoria excepto un caso que requirió de internación por 24 horas. La resolución completa de los síntomas ocurrió antes de la primera semana. Discusión y conclusiones: la presentación de una colitis aguda, auto limitada luego de un procedimiento endoscópico normal con tenesmo y diarrea sanguinolenta en las 48 horas debe suponer este diagnóstico...

Complicaciones de la videocolonoscopía. Estudio institucional / Colonoscopy complications. Institutional study

Introducción: la colonoscopía es uno de los métodos de estudio del colon de referencia para el proctólogo. Es un método diagnóstico y terapéutico seguro. La incidencia de complicaciones es del 0,1 al 3 por ciento. La perforación del colon y la hemorragia son las más frecuentes. Objetivo: analizar las complicaciones de la videocolonoscopía en una serie institucional. Diseño: análisis prospectivo y consecutivo. Serie institucional. Pacientes: Se analizaron todas las videocolonoscopías diagnósticas y terapéuticas, realizadas en el período comprendido entre enero de 1996 y julio 2004. Lugar: Hospital Privado de Comunidad. Métodos: número total de complicaciones atribuidas al procedimiento. No se registraron las complicaciones relacionadas con la anestesia. Se evaluaron: patología colónica previa, sexo y edad, indicación, admisión, tipo de endoscopia, tipo de complicación, número y sitio de la complicación, tamaño de la perforación, presentación clínica y metodología diagnóstica, momento del diagnóstico y tratamiento (tiempo, procedimiento, mortalidad y morbilidad postoperatoria). Resultados: de 4.790 colonoscopías, 4.512 fueron ambulatorias. Fueron 15 lesiones (0,3 por ciento): 8 perforaciones de colon (0,16 por ciento), 1 hemorragia postpolipectomía (0,02 por ciento), 1 lesión de bazo (0,02 por ciento) y 5 rectitis (0,1 por ciento). El 53,9 por ciento de las endoscopias fueron diagnósticas. La incidencia de complicaciones luego de colonoscopías diagnósticas y terapéuticas fue del 0,18 por ciento (9 casos) y del 0,15 por ciento (6 casos), respectivamente. Todas fueron tratadas oportunamente. La morbilidad global de la serie fue del 0,06 por ciento y 20 por ciento del total de lesiones. No hubo mortalidad. Discusión y conclusiones: la incidencia de complicaciones de la colonoscopía es baja, pero cuando estas ocurren están asociadas a una elevada morbimortalidad. Las más frecuentes son la perforación y la hemorragia. El tipo de tratamiento se relaciona con el momento del diagnóstico, y la severidad de la lesión. El tratamiento quirúrgico temprano es el Standard oro aunque el manejo no operatorio es adecuado sólo si es altamente selectivo.