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1.
J Craniomaxillofac Surg ; 51(5): 309-315, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37353405

RESUMEN

In this study, 100 consecutive scheduled transoral condylectomies for unilateral condylar hyperplasia were included. The safety and surgical performances were assessed, using the operating time, conversion rate and complication rate. The conversion rate learning curve was evaluated with a learning curve cumulative summation (LC-CUSUM). The total conversion rate was 8.0%. The LC-CUSUM for conversion signaled at the 53th procedure, indicating sufficient evidence had accumulated that the surgeon had achieved competence. For procedures 54-100, the conversion rate was 4.0%. The operating time for the transoral condylectomy was 41.5 ± 15.3 min; when a conversion was necessary, the operating time was 101.4 ± 28.3 min (p < 0.05). The estimated operating time in the post-learning phase was 37 min, this was reached after approximately 47 procedures. There was 1 major complication of a permanent inferior alveolar nerve hypoesthesia. The complication rate was not significantly decreased after the learning curve. Within the limitations of the study, it seems that transoral condylectomy for UCH is a safe procedure with several advantages over the traditional preauricular approach. Surgeons starting this procedure should be aware of the potential complications and of the learning curve of approximately 53 procedures.


Asunto(s)
Enfermedades Óseas , Enfermedades Estomatognáticas , Humanos , Cóndilo Mandibular/cirugía , Cóndilo Mandibular/patología , Curva de Aprendizaje , Estudios Retrospectivos , Hiperplasia/cirugía , Hiperplasia/patología , Asimetría Facial/cirugía , Enfermedades Óseas/patología
3.
Int J Colorectal Dis ; 37(2): 293-299, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35006332

RESUMEN

AIM: Neoadjuvant chemotherapy (NACRT) can make decompensated patients more vulnerable prior to rectal surgery. Prehabilitation is an intervention which enhances functional capacity to withstand the stress of surgery. The aim of this review was to evaluate the impact of prehabilitation for patients undergoing rectal surgery on physical fitness and clinical outcomes and to establish feasibility of prehabilitation. METHODS: An analysis of the literature was conducted of PubMed, the Cochrane Library, MEDLINE, EMBASE and ScienceDirect. Articles were initially included based on their title and abstracts reviewed. Full-text copies of those selected were obtained for confirmation of inclusion. RESULTS: Eight studies were included. Heterogenicity was observed in the structure of exercise programmes. Improvements in physical fitness were observed in six studies. One study demonstrated a statistically significant improvement in quality of life. The prehabilitation programmes were shown to be feasible, with high completion rates. No adverse events were reported. There was limited data regarding the impact of prehabilitation on postoperative outcomes. CONCLUSION: Current evidence on prehabilitation in rectal surgery has considerable heterogenicity in both structure of programmes and outcome measures. Standardisation is required for future evaluation of the impact on outcomes. A trimodal approach of exercise, nutritional and psychological interventions has been employed in similar programmes, and should be used in rectal surgery. The intervention should be tailored to the patient and environment. This review highlights the benefits, safety and feasibility of prehabilitation and provides a platform for consensus-building for international trials.


Asunto(s)
Procedimientos Quirúrgicos del Sistema Digestivo , Calidad de Vida , Humanos , Terapia Neoadyuvante , Complicaciones Posoperatorias , Cuidados Preoperatorios , Ejercicio Preoperatorio
5.
Ir Med J ; 115(No.9): 675, 2022 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-36920414
7.
Br J Surg ; 108(5): 469-476, 2021 05 27.
Artículo en Inglés | MEDLINE | ID: mdl-33748848

RESUMEN

BACKGROUND: The role of laparoscopic rectal cancer surgery has been questioned owing to conflicting reports on pathological outcomes from recent RCTs. However, it is unclear whether these pathological markers and the surgical approach have an impact on oncological outcomes. This study assessed oncological outcomes of laparoscopic and open rectal cancer resections. METHODS: A meta-analysis of RCTs was performed. Primary endpoints included oncological outcomes (disease-free survival (DFS), overall survival (OS), local recurrence). Secondary endpoints included surrogate markers for the quality of surgical resection. RESULTS: Twelve RCTs including 3744 patients (2133 laparoscopic, 1611 open) were included. There was no significant difference in OS (hazard ratio (HR) 0.87, 95 per cent c.i. 0.73 to 1.04; P = 0.12; I2 = 0 per cent) and DFS (HR 0.95, 0.81 to 1.11; P = 0.52; I2 = 0 per cent) between laparoscopic and open rectal resections. There was no significant difference in locoregional (odds ratio (OR) 1.03, 95 per cent c.i. 0.72 to 1.48; P = 0.86; I2 = 0 per cent) or distant (OR 0.87, 0.70 to 1.08; P = 0.20; I2 = 7 per cent) recurrence between the groups. Achieving a successful composite score (intact mesorectal excision, clear circumferential resection margin and distal margin) was significantly associated with improved DFS (OR 0.55, 0.33 to 0.74; P < 0.001; I2 = 0 per cent). An intact or acceptable mesorectal excision (intact mesorectal excision with or without superficial defects) had no impact on DFS. Finally, a positive CRM was associated with worse DFS. CONCLUSION: Well performed surgery (laparoscopic or open) achieves excellent oncological outcomes with very little difference between the two modalities. The advantage and benefit of minimally invasive surgery should be assessed on an individual basis.


Asunto(s)
Laparoscopía , Proctectomía/métodos , Neoplasias del Recto/cirugía , Supervivencia sin Enfermedad , Humanos , Márgenes de Escisión , Ensayos Clínicos Controlados Aleatorios como Asunto
8.
Prostaglandins Other Lipid Mediat ; 152: 106499, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33035691

RESUMEN

Prostaglandin E2 (PGE2) is found throughout the gastrointestinal tract in a diverse variety of functions and roles. The recent discovery of four PGE2 receptor subtypes in intestinal muscle layers as well as in the enteric plexus has led to much interest in the study of their roles in gut motility. Gut dysmotility has been implicated in functional disease processes including irritable bowel syndrome (IBS) and slow transit constipation, and lubiprostone, a PGE2 derivative, has recently been licensed to treat both conditions. The diversity of actions of PGE2 in the intestinal tract is attributed to its differing effects on its downstream receptor types, as well as their varied distribution in the gut, in both health and disease. This review aims to identify the role and distribution of PGE2 receptors in the intestinal tract, and aims to elucidate their distinct role in gut motor function, with a specific focus on functional intestinal pathologies.


Asunto(s)
Motilidad Gastrointestinal , Terapia Molecular Dirigida , Subtipo EP2 de Receptores de Prostaglandina E , Humanos
9.
Int J Colorectal Dis ; 36(3): 551-558, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33242114

RESUMEN

BACKGROUND: Locoregional recurrence (LR) remains a problem for patients with lower rectal cancer despite standardized surgery and improved neoadjuvant treatment regimens. Lateral pelvic lymph node dissection (LPLND) has been routine practice for some time in the Orient/East, but other regions have concerns about morbidity. As perioperative care and surgical approaches are refined, this has been revisited for selected patients. The question as to whether LPLND improves oncological outcomes was explored here. METHODS: A systematic review of patients who underwent TME with or without LPLND from 2000 to 2020 was performed. The primary endpoint was the rate of LR between the two groups. RESULTS: Seven papers met the predefined search criteria in which 2000 patients underwent TME alone, while 1563 patients had TME and LPLND. The rate of LR was marginally higher with TME alone when compared with TME plus LPLND, but this result was not statistically significant (9.8 vs 9.4%, odds ratio 0.75, 95% CI 0.41-1.38, *p = 0.35). In addition, four studies reported on distant recurrence rates, with TME and LPLND showing a slight reduction in overall rates (27.3 vs 29.9%, respectively, OR 0.65, 95% CI 0.45-0.92, *p = 0.02). CONCLUSION: The addition of LPLND to TME is not associated with a significantly lower risk of LR in patients who undergo surgery for lower rectal cancer.


Asunto(s)
Recurrencia Local de Neoplasia , Neoplasias del Recto , Humanos , Escisión del Ganglio Linfático , Terapia Neoadyuvante , Neoplasias del Recto/cirugía
10.
Colorectal Dis ; 22 Suppl 2: 5-28, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32638537

RESUMEN

AIM: The goal of this European Society of Coloproctology (ESCP) guideline project is to give an overview of the existing evidence on the management of diverticular disease, primarily as a guidance to surgeons. METHODS: The guideline was developed during several working phases including three voting rounds and one consensus meeting. The two project leads (JKS and EA) appointed by the ESCP guideline committee together with one member of the guideline committee (WB) agreed on the methodology, decided on six themes for working groups (WGs) and drafted a list of research questions. Senior WG members, mostly colorectal surgeons within the ESCP, were invited based on publication records and geographical aspects. Other specialties were included in the WGs where relevant. In addition, one trainee or PhD fellow was invited in each WG. All six WGs revised the research questions if necessary, did a literature search, created evidence tables where feasible, and drafted supporting text to each research question and statement. The text and statement proposals from each WG were arranged as one document by the first and last authors before online voting by all authors in two rounds. For the second voting ESCP national representatives were also invited. More than 90% agreement was considered a consensus. The final phrasing of the statements with < 90% agreement was discussed in a consensus meeting at the ESCP annual meeting in Vienna in September 2019. Thereafter, the first and the last author drafted the final text of the guideline and circulated it for final approval and for a third and final online voting of rephrased statements. RESULTS: This guideline contains 38 evidence based consensus statements on the management of diverticular disease. CONCLUSION: This international, multidisciplinary guideline provides an up to date summary of the current knowledge of the management of diverticular disease as a guidance for clinicians and patients.


Asunto(s)
Enfermedades Diverticulares , Colon , Consenso , Enfermedades Diverticulares/terapia , Humanos
13.
Br J Surg ; 107(5): 606-612, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-32149397

RESUMEN

BACKGROUND: The incidence of rectal cancer among adults aged less than 50 years is rising. Survival data are limited and conflicting, and the oncological benefit of standard neoadjuvant and adjuvant therapies is unclear. METHODS: Disease-specific outcomes of patients diagnosed with rectal cancer undergoing surgical resection with curative intent between 2006 and 2016 were analysed. RESULTS: A total of 797 patients with rectal cancer were identified, of whom 685 had surgery with curative intent. Seventy patients were younger than 50 years and 615 were aged 50 years or more. Clinical stage did not differ between the two age groups. Patients aged less than 50 years were more likely to have microsatellite instability (9 versus 1·6 per cent; P = 0·003) and Lynch syndrome (7 versus 0 per cent; P < 0·001). Younger patients were also more likely to receive neoadjuvant chemoradiotherapy (67 versus 53·3 per cent; P = 0·003) and adjuvant chemotherapy (41 versus 24·2 per cent; P = 0·006). Five-year overall survival was better in those under 50 years old (80 versus 72 per cent; P = 0·013). The 5-year disease-free survival rate was 81 per cent in both age groups (P = 0·711). There were no significant differences in the development of locoregional recurrence or distant metastases. CONCLUSION: Despite accessing more treatment, young patients have disease-specific outcomes comparable to those of their older counterparts.


ANTECEDENTES: La incidencia de cáncer de recto entre adultos menores de 50 años está aumentando. Los datos de supervivencia son limitados y contradictorios, y el beneficio oncológico de los tratamientos neoadyuvantes y adyuvantes estándares no está claro. MÉTODOS: Se analizaron los resultados específicos relacionados con la enfermedad en pacientes diagnosticados de cáncer de recto operados con intención curativa entre 2006 y 2016. RESULTADOS: Se identificaron un total de 797 pacientes con cáncer de recto, de los cuales 685 fueron intervenidos quirúrgicamente con intención curativa. Setenta tenían menos de 50 años y 615 tenían 50 años o más. No hubo diferencias en el estadio clínico entre los dos grupos de edad. Los pacientes menores de 50 años tenían más probabilidades de tener inestabilidad de microsatélites (9% versus 2%, P = 0,003) y síndrome de Lynch (7% versus 0%, P ≤ 0,001). La supervivencia global a los 5 años fue mayor en los pacientes de menos de 50 años (80% y 72%; P = 0,013). La supervivencia libre de enfermedad a los 5 años fue del 81% en ambos grupos de edad (P = 0,711). No hubo diferencias significativas en el desarrollo de recidiva locorregional o metástasis a distancia. Los pacientes más jóvenes tenían más probabilidades de recibir quimiorradioterapia neoadyuvante (67% versus 53%, P = 0,003) y quimioterapia adyuvante (41% versus 24%, P = 0,006). CONCLUSIÓN: A pesar de tener acceso a más tratamientos, los pacientes jóvenes han presentado resultados específicos relacionados con la enfermedad comparables a sus homólogos de mayor edad.


Asunto(s)
Neoplasias del Recto/patología , Neoplasias del Recto/cirugía , Edad de Inicio , Quimioradioterapia Adyuvante , Quimioterapia Adyuvante , Neoplasias Colorrectales Hereditarias sin Poliposis/patología , Neoplasias Colorrectales Hereditarias sin Poliposis/cirugía , Humanos , Inestabilidad de Microsatélites , Persona de Mediana Edad , Terapia Neoadyuvante , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Neoplasias del Recto/genética , Estudios Retrospectivos , Factores de Riesgo , Análisis de Supervivencia
14.
Tech Coloproctol ; 24(6): 527-543, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32124112

RESUMEN

BACKGROUND: Surgical strategies for acute perforated diverticulitis with generalised peritonitis remain controversial. This study aimed to meta-analyse trials comparing primary resection and anastomosis (PRA) to Hartmann's procedure (HP) for Hinchey III/IV diverticulitis. METHODS: A systematic literature search was conducted to identify observational studies and randomised control trials (RCTs) of patients with Hinchey III/IV diverticulitis undergoing sigmoidectomy that compared PRA to HP. The methodological quality of the included studies was assessed systematically (Newcastle-Ottawa, Jadad and Cochrane risk of bias scores) and a meta-analysis was performed. RESULTS: After removal of duplicates, 12 studies including 4 RCTs were identified. The analysis included 918 patients, of whom 367 (39.98%) underwent PRA. Both the initial stoma rate (risk ratio [RR] persistent stoma 0.43, 95% confidence interval [CI] 0.26, 0.71, p = 0.001; I2 = 99%, p < 0.0001) and the rate of permanent stoma after combining the first (emergency surgery) and second (stoma reversal) procedures were lower in the PRA group. There was no difference in in 30-day mortality; however, PRA resulted in a reduction in overall mortality as well as major complications after the initial operation (RR 0.67, 95% CI 0.46, 0.97, p = 0.03; I2 = 22%, p = 0.26), stoma reversal (RR 0.48, 95% CI 0.26, 0.92, p = 0.03; I2 = 0%, p = 0.58) and when combining both procedures (RR 0.67, 95% CI 0.51, 0.88, p = 0.005; I2 = 0%, heterogeneity p = 0.58). A subgroup analysis of stoma reversal rates using data from only RCTs were consistent (RR permanent stoma, 0.33, 95% CI 0.13, 0.85, p = 0.02; I2 = 77%, p = 0.004) with the findings of the overall analysis. CONCLUSIONS: This meta-analysis demonstrates that PRA used in the management of haemodynamically stable patients with Hinchey grade III/IV diverticulitis leads to a lower overall persistent stoma rate, with reduced morbidity compared with the traditional management.


Asunto(s)
Diverticulitis del Colon , Diverticulitis , Perforación Intestinal , Peritonitis , Anastomosis Quirúrgica , Colostomía , Diverticulitis del Colon/complicaciones , Diverticulitis del Colon/cirugía , Humanos , Perforación Intestinal/etiología , Perforación Intestinal/cirugía , Peritonitis/etiología , Peritonitis/cirugía , Resultado del Tratamiento
16.
Colorectal Dis ; 22(9): 1101-1107, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-31869511

RESUMEN

INTRODUCTION: The gastrointestinal microbiome has been suggested to contribute to the development of both primary and secondary colorectal cancer. Despite advances in understanding the prognostic and predictive value of clinico-pathological parameters, the underlying mechanisms that result in progression to metastatic disease have yet to be defined. The metastatic cascade involves a number of sequential steps, including detachment of tumour cells from the primary site, intravasation and dissemination within the circulatory and lymphatic systems, with extravasation and proliferation at a secondary site. OBJECTIVE: An analysis of the literature relating to the gastrointestinal microbiome and its role in colorectal metastasis was conducted. This review aims to examine the current evidence supporting a role for the microbiome in colorectal metastasis and to describe the mechanisms by which it may contribute to metastatic progression. CONCLUSION: The invasive pathways utilized by bacteria and how they may be manipulated by tumour cells for migration and metastasis are presented and the potential of the intestinal microbiome as a therapeutic target in colorectal carcinogenesis and metastasis is detailed here.


Asunto(s)
Neoplasias Colorrectales , Microbioma Gastrointestinal , Microbiota , Humanos , Metástasis de la Neoplasia , Pronóstico
19.
World J Surg ; 43(12): 3224-3231, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31482344

RESUMEN

BACKGROUND: Acute mesenteric ischaemia (AMI) is a life-threatening surgical emergency resulting from thromboembolic occlusion of the mesenteric vasculature. Traditional management of AMI has been open revascularisation with or without bowel resection-a procedure which carries considerable morbidity and mortality in an already unwell, compromised patient. Endovascular and more minimally invasive management approaches to AMI have been reported. Proponents of endovascular management suggest this approach may be associated with reduced morbidity and mortality compared with open surgery. OBJECTIVES: To assess the impact of endovascular approach for AMI on mortality and need for subsequent laparotomy and/or bowel resection. DATA SOURCES: The search bodies PubMed and Medline were interrogated. ELIGIBILITY CRITERIA, PARTICIPANTS AND INTERVENTIONS: All studies in English with greater than 10 patients examining outcomes for patients undergoing endovascular intervention for acute mesenteric ischaemia were included. All patients over 18 years presenting with a diagnosis of acute mesenteric ischaemia secondary to an arterial thromboembolic source were included. Studies examining endovascular intervention alone or endovascular and open intervention were selected. RESULTS: The 30-day mortality for endovascular approach from all 13 studies was 16-42%. Of the 7 comparative studies including results of open revascularisation, the 30-day mortality for patient treated with an endovascular approach was 15-39% versus 33-50% for open revascularisation. Laparotomy rates post-initial endovascular intervention ranged from 13 to 73%. Bowel resection post-endovascular therapy ranged from 14 to 40% among studies. Concerning 7 comparative studies for open versus endovascular revascularisation, the rate of bowel resection in the endovascular group ranged 14-28% and 33-63% in the open cohort. Endovascular intervention also demonstrated lower median length (s) of bowel resected. LIMITATIONS: Heterogeneity of studies and patient populations studied including selection bias. CONCLUSIONS AND IMPLICATIONS OF FINDINGS: Endovascular management may be associated with reduced mortality and need for/length of bowel resection compared with the traditional open approach, but there remains a paucity of robust data to support this. The available literature illustrates that a subgroup of patients without haemodynamic compromise and more insidious onset may garner benefit from endovascular intervention.


Asunto(s)
Procedimientos Endovasculares/métodos , Isquemia Mesentérica/cirugía , Enfermedad Aguda , Humanos , Isquemia Mesentérica/mortalidad
20.
Br J Surg ; 106(12): 1697-1704, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31393608

RESUMEN

INTRODUCTION: Appendicectomy may reduce relapses and need for medication in patients with ulcerative colitis, but long-term prospective data are lacking. This study aimed to analyse the effect of appendicectomy in patients with refractory ulcerative colitis. METHODS: In this prospective multicentre cohort series, all consecutive patients with refractory ulcerative colitis referred for proctocolectomy between November 2012 and June 2015 were counselled to undergo laparoscopic appendicectomy instead. The primary endpoint was clinical response (reduction of at least 3 points in the partial Mayo score) at 12 months and long-term follow-up. Secondary endpoints included endoscopic remission (endoscopic Mayo score of 1 or less), failure (colectomy or start of experimental medication), and changes in Inflammatory Bowel Disease Questionnaire (IBDQ) (range 32-224), EQ-5D™ and EORTC-QLQ-C30-QL scores. RESULTS: A total of 28 patients (13 women; median age 40·5 years) underwent appendicectomy. The mean baseline IBDQ score was 127·0, the EQ-5D™ score was 0·65, and the EORTC-QLQ-C30-QL score was 41·1. At 12 months, 13 patients had a clinical response, five were in endoscopic remission, and nine required a colectomy (6 patients) or started new experimental medical therapy (3). IBDQ, EQ-5D™ and EORTC-QLQ-C30-QL scores improved to 167·1 (P < 0·001), 0·80 (P = 0·003) and 61·0 (P < 0·001) respectively. After a median of 3·7 (range 2·3-5·2) years, a further four patients required a colectomy (2) or new experimental medical therapy (2). Thirteen patients had a clinical response and seven were in endoscopic remission. The improvement in IBDQ, EQ-5D™ and the EORTC-QLQ-C30-QL scores remained stable over time. CONCLUSION: Appendicectomy resulted in a clinical response in nearly half of patients with refractory ulcerative colitis and a substantial proportion were in endoscopic remission. Elective appendicectomy should be considered before proctocolectomy in patients with therapy-refractory ulcerative colitis.


ANTECEDENTES: La apendicectomía puede reducir las recaídas y la necesidad de medicación en pacientes con colitis ulcerosa (ulcerative colitis, UC), sin embargo, faltan datos a largo plazo obtenidos de forma prospectiva. El objetivo de este estudio fue analizar el efecto de la apendicectomía en pacientes con UC refractarios al tratamiento. MÉTODOS: En esta serie prospectiva de cohortes multicéntrica, a todos los pacientes consecutivos con UC refractaria remitidos para proctocolectomía entre noviembre de 2012 y junio de 2015 se les recomendó en su lugar someterse a una apendicectomía laparoscópica. El criterio de valoración principal fue la respuesta clínica (disminución de ≥ 3 puntos del sistema de puntuación parcial de Mayo que varía de 0 a 9) a los 12 meses y en el seguimiento a largo plazo. Los criterios de valoración secundarios incluyeron la remisión endoscópica (puntuación endoscópica de Mayo ≤ 1), fracaso (colectomía o inicio de medicación experimental) y cambios en el IBDQ (rango 32-224), EQ-5D y EORTC-QLQ-C30-QL. RESULTADOS: En total, 28 pacientes (13 mujeres, mediana de edad 40,5) se sometieron a una apendicectomía. El IBDQ de referencia promedio fue de 127,0; el EQ-5D 0,65 y el EORTC-QLQ-C30-QL 41,1. A los 12 meses, 13 pacientes presentaban una respuesta clínica, cinco estaban en remisión endoscópica y nueve precisaron colectomía (n = 6) o un nuevo tratamiento médico experimental (n = 3). El IBDQ, EQ-5D y EORTC-QLQ-C30-QL mejoraron a 167,1 (P < 0,001); 0,80 (P = 0,003) y 61,0 (P < 0,001) respectivamente. Después de una mediana de 3,7 años (rango 2,3-5,2), otros cuatro pacientes requirieron una colectomía (n = 2) o un nuevo tratamiento médico experimental (n = 2). Trece pacientes presentaron respuesta clínica y siete se encontraban en remisión endoscópica. La mejora del IBDQ, el EQ-5D y el EORTC-QLQ-C30-QL se mantuvo estable a lo largo del tiempo. CONCLUSIÓN: La apendicectomía consiguió una respuesta clínica en casi la mitad de los pacientes con UC refractaria. La apendicectomía electiva debería ser considerada antes que la proctocolectomía en pacientes con UC refractaria al tratamiento.


Asunto(s)
Apendicectomía , Colitis Ulcerosa/cirugía , Corticoesteroides/uso terapéutico , Adulto , Colitis Ulcerosa/tratamiento farmacológico , Femenino , Humanos , Factores Inmunológicos/uso terapéutico , Laparoscopía , Masculino , Persona de Mediana Edad , Proctocolectomía Restauradora , Estudios Prospectivos , Calidad de Vida , Inducción de Remisión , Índice de Severidad de la Enfermedad
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