RESUMEN
BACKGROUND: Perianal fistulas are a challenging manifestation of Crohn's disease. Best medical and surgical therapy results in only about a third of patients remaining in remission at one year on maintenance treatment and sustained healing is often elusive. There is little published data on patient perspective of living with the condition or coping strategies in the face of non-curative/non-definitive treatment. We aimed to understand the experience of living with perianal fistula(s) and their impact on quality of life and routine functioning. METHODS: This exploratory qualitative study used purposive sampling to recruit participants with current / previous diagnosis of Crohn's anal fistulas, from national IBD / bowel disease charities. The "standards for reporting qualitative research" (SRQR) recommendations were followed. Unstructured individual face-to-face interviews were audio recorded, transcribed and analysed thematically. Early themes were reviewed by the study team including patient advocates, clinicians and qualitative researchers. RESULTS: Twelve interviews were conducted, achieving apparent data saturation. Three broad themes were uncovered: Burden of symptoms; Burden of treatment; and Impact on emotional, physical and social well-being. Each included several sub-themes, with considerable interplay between these. The impact of perianal fistula(s) on patients with CD is intense and wide reaching, negatively affecting intimate, close and social relationships. Fistulas cause losses in life and work-related opportunities, and treatments can be difficult to tolerate. CONCLUSION: Crohn's perianal fistulas exert a heavy negative physical and emotional impact on patients. These findings will inform development of a patient reported outcome measure to assess treatment effectiveness and quality of life for patients living with this challenging condition.
Asunto(s)
Costo de Enfermedad , Enfermedad de Crohn/psicología , Medición de Resultados Informados por el Paciente , Calidad de Vida , Fístula Rectal/psicología , Adolescente , Adulto , Enfermedad de Crohn/complicaciones , Femenino , Humanos , Masculino , Persona de Mediana Edad , Investigación Cualitativa , Fístula Rectal/etiología , Adulto JovenRESUMEN
OBJECTIVE: Lack of standardised outcomes hampers effective analysis and comparison of data when comparing treatments in fistulising perianal Crohn's disease (pCD). Development of a standardised set of outcomes would resolve these issues. This study provides the definitive core outcome set (COS) for fistulising pCD. DESIGN: Candidate outcomes were generated through a systematic review and patient interviews. Consensus was established via a three-round Delphi process using a 9-point Likert scale based on how important they felt it was in determining treatment success culminating in a final consensus meeting. Stakeholders were recruited nationally and grouped into three panels (surgeons and radiologists, gastroenterologists and IBD specialist nurses, and patients). Participants received feedback from their panel (in the second round) and all participants (in the third round) to allow refinement of their scores. RESULTS: A total of 295 outcomes were identified from systematic reviews and interviews that were categorised into 92 domains. 187 stakeholders (response rate 78.5%) prioritised 49 outcomes through a three-round Delphi study. The final consensus meeting of 41 experts and patients generated agreement on an eight domain COS. The COS comprised three patient-reported outcome domains (quality of life, incontinence and a combined score of patient priorities) and five clinician-reported outcome domains (perianal disease activity, development of new perianal abscess/sepsis, new/recurrent fistula, unplanned surgery and faecal diversion). CONCLUSION: A fistulising pCD COS has been produced by all key stakeholders. Application of the COS will reduce heterogeneity in outcome reporting, thereby facilitating more meaningful comparisons between treatments, data synthesis and ultimately benefit patient care.
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Enfermedad de Crohn/terapia , Evaluación de Resultado en la Atención de Salud , Fístula Rectal/terapia , Conferencias de Consenso como Asunto , Enfermedad de Crohn/patología , Técnica Delphi , Progresión de la Enfermedad , Incontinencia Fecal/etiología , Humanos , Entrevistas como Asunto , Medición de Resultados Informados por el Paciente , Calidad de Vida , Fístula Rectal/patología , Proyectos de Investigación , Factores de Riesgo , Revisiones Sistemáticas como AsuntoRESUMEN
BACKGROUND: The characteristics of patients who develop a fistula-in-ano after an anorectal abscess are unclear. OBJECTIVE: Our study explored this relationship and patient factors associated with fistula development. DESIGN: International Classification of Diseases, 10 Revision, and Classification of Interventions and Procedures, version 4, codes were used to identify all of the patients with a primary anorectal abscess. Multivariable analysis was used to identify factors predictive of fistula formation. SETTINGS: The study was conducted in a district general hospital. PATIENTS: Patients with anorectal abscess who were admitted to our institution (2004-2015) were included. MAIN OUTCOMES MEASURES: The rate of subsequent fistula formation was measured. RESULTS: A total of 1970 abscess patients were identified; 70.0% (n = 1379) were men, and 7.3% (n = 144) had Crohn's disease. Fistulas occurred in 16.2% (n = 319) at a median of 7 months (interquartile range, 3-7 mo). Patients with Crohn's disease were more than twice as likely to develop a fistula than patients without Crohn's disease (32.6% vs 14.9%; OR = 2.5 (95% CI, 1.7-3.7); p < 0.001). Patients with Crohn's disease with a fistula were more likely to be women (55.3% vs 34.6%; p = 0.007) and aged <30 years (51.1% vs 24.3%; p< 0.001) versus patients without Crohn's disease with a fistula. At multivariable analysis of the entire cohort, male sex (OR = 0.7 (95% CI, 0.5-0.9); p = 0.005) and diabetes mellitus (OR = 0.5 (95% CI, 0.3-0.9); p = 0.027) were associated with a reduced likelihood of developing a fistula after abscess formation. LIMITATIONS: The study was limited by its single-center scope, retrospective analysis, and lack of a standardized definition for Crohn's disease. CONCLUSIONS: Abscesses are more common in men, but progression to fistula is more likely in women. The rate of fistula progression in Crohn's disease is twice that in patients without Crohn's disease. Identification of patients at risk may help delineate those who will benefit from a more conservative surgical approach, enhanced follow-up, or investigation after abscess drainage. See Video Abstract at http://links.lww.com/DCR/A798.
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Absceso , Enfermedades del Ano , Enfermedad de Crohn/epidemiología , Disección , Drenaje , Complicaciones Posoperatorias , Fístula Rectal , Absceso/diagnóstico , Absceso/cirugía , Adulto , Enfermedades del Ano/diagnóstico , Enfermedades del Ano/epidemiología , Enfermedades del Ano/cirugía , Disección/efectos adversos , Disección/métodos , Drenaje/efectos adversos , Drenaje/métodos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/epidemiología , Pronóstico , Fístula Rectal/diagnóstico , Fístula Rectal/epidemiología , Fístula Rectal/etiología , Estudios Retrospectivos , Factores de Riesgo , Factores Sexuales , Reino Unido/epidemiologíaRESUMEN
BACKGROUND: Familial adenomatous polyposis-related desmoid tumors can present with a liquefied center containing gas, accompanied by abdominal pain and sepsis. To date the optimal management of such patients has not been documented. OBJECTIVE: The aim of this study was to review our experience of managing these desmoids grouped together as "intra-abdominal desmoids with air-fluid level" and present a management algorithm. DESIGN: This is a retrospective study of prospectively maintained polyposis registry database. SETTING: This study was conducted at a tertiary referral center specializing in familial adenomatous polyposis and desmoid disease. PATIENTS: Nine patients with intra-abdominal desmoid and air-fluid level were analyzed for the purpose of this study. RESULTS: Two hundred and forty-six patients were identified with desmoid tumor. Of these, a total of 9 patients had an intra-abdominal desmoid with air-fluid level; 7 were women. Age range at diagnosis was 20 to 41 years. The median time from primary surgery to desmoid tumor development was 24 months (range, 0-48 months), and the median time for further progression to air-fluid level was 24 months (range, 0-226 months). Desmoid tumor size ranged from 10 cm to greater than 20 cm in diameter. Two patients were successfully managed with antibiotics alone, and 2 patients were managed with percutaneous drainage and antibiotics. The other 5 patients required surgical intervention involving either excision or drainage with or without proximal defunctioning/exclusion. There was a single 30-day mortality. LIMITATION: This study was limited by the small number of patients. CONCLUSIONS: The majority of intra-abdominal desmoids with an air-fluid level require surgical intervention. Antibiotics and percutaneous drainage are only successful in a limited number of patients. We present our current treatment algorithm based on this experience.
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Poliposis Adenomatosa del Colon/diagnóstico , Fibromatosis Abdominal/patología , Adulto , Algoritmos , Antibacterianos/administración & dosificación , Estudios de Cohortes , Terapia Combinada , Procedimientos Quirúrgicos del Sistema Digestivo , Drenaje , Femenino , Fibromatosis Abdominal/microbiología , Fibromatosis Abdominal/terapia , Humanos , Masculino , Peritonitis/tratamiento farmacológico , Peritonitis/etiología , Peritonitis/microbiología , Sistema de Registros , Estudios Retrospectivos , Sepsis/tratamiento farmacológico , Sepsis/etiología , Sepsis/microbiología , Tomografía Computarizada por Rayos X , Adulto JovenRESUMEN
BACKGROUND: Juvenile polyposis syndrome is phentoypically and genotypically heterogeneous. It is associated with an increased risk of GI cancers, and surveillance is recommended. Few data exist that detail the outcomes of surveillance in juvenile polyposis syndrome. OBJECTIVE: The aim of this study was to review clinical features, genetic mutations, and long-term outcome data in patients with juvenile polyposis syndrome. DESIGN: This study is a retrospective review. SETTING: The Polyposis Registry, St Mark's Hospital, was used in the performance of this study. PATIENTS: Patients with juvenile polyposis syndrome who were followed up at our institution were included. RESULTS: Forty-four patients (27 male) from 30 kindreds were included. Fifteen were diagnosed by screening, and 29 presented symptomatically. Nineteen patients had SMAD4 mutation and 9 had BMPR1A mutation. Five patients (11%) had valvular heart disease. Telangiectasia/vascular abnormalities were observed in 4 (9%) patients, and macrocephaly was observed in 5 (11%). Six patients (14%) developed cancer; 4 had cancer at the time of diagnosis of juvenile polyposis syndrome, 3 developed cancer while on surveillance (1 patient had a second primary). All patients with advanced upper GI disease had SMAD4 mutations. Where germline mutation was known, all patients with telangiectasia had SMAD4 mutation. Seven patients required GI surgery at our institution: colectomy and ileorectal anastomosis (1), restorative proctocolecotomy (1), anteroposterior excision for rectal cancer (1), gastrectomy (2), and laparotomy and intraoperative enteroscopy (1). There were no complications of endoscopic surveillance. Colonic polyps predominated; 535 of 767 (69.8%) of colonic polyps were right sided. One patient had a solitary significant small-bowel polyp. Sixty-five juvenile polyps contained dysplasia (mild to moderate). Two patients had severe dysplasia or cancer found in carpeting polyps. LIMITATIONS: This is a retrospective review. The cohort size, although modest, is good for such a rare condition. CONCLUSION: Extraintestinal features are common. Gastrointestinal surveillance is safe. Most colonic polyps are right sided, and detecting dysplasia is uncommon. Carpeting polyps are of particular concern.
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Poliposis Intestinal/congénito , Síndromes Neoplásicos Hereditarios/genética , Síndromes Neoplásicos Hereditarios/patología , Adolescente , Adulto , Anciano , Receptores de Proteínas Morfogenéticas Óseas de Tipo 1/genética , Niño , Preescolar , Progresión de la Enfermedad , Endoscopía Gastrointestinal , Femenino , Estudios de Seguimiento , Genotipo , Humanos , Poliposis Intestinal/genética , Poliposis Intestinal/patología , Poliposis Intestinal/cirugía , Masculino , Persona de Mediana Edad , Mutación , Síndromes Neoplásicos Hereditarios/cirugía , Fenotipo , Sistema de Registros , Estudios Retrospectivos , Proteína Smad4/genética , Resultado del TratamientoRESUMEN
INTRODUCTION: Anti-TNF therapy is recommended as treatment for patients with Crohn´s perianal fistulas. However, a significant proportion of patients have a sub-optimal response to anti-TNF therapy. Higher serum levels of anti-TNF agents have been associated with improved outcomes in perianal Crohn's disease. Currently, it is unknown whether anti-TNF agent levels can be detected in tissue from fistula tracts themselves and whether this is associated with response. AIMS AND METHODS: We undertook a pilot study to measure fistula tissue levels of anti-TNF medication (infliximab and adalimumab). We used a previously validated targeted proteomic technique, employing ultraperformance liquid chromatography-mass spectrometry, to detect/quantify anti-TNF drugs. Biopsies were obtained from fistula tracts of patients with Crohn's disease on maintenance treatment; with idiopathic (cryptoglandular) fistula tissues used as negative controls as well as positive controls (by spiking the latter tissues with anti-TNF drugs). RESULTS: Tissue was sampled from the fistula tracts of seven patients with Crohn's perianal disease (five patients were on adalimumab and two patients were on infliximab). The anti-TNF drugs, infliximab and adalimumab, were not detected in fistula samples from any of the Crohn's patients despite detection in 'spiked' positive control samples. CONCLUSION: Absence of detection of the anti-TNF drugs in fistula tissue raises the question on the role of tissue penetrance of anti-TNF drugs in response to therapy. Further work is required in a larger number of patients to validate the findings observed and investigate if any correlation exists between tissue and serum levels of anti-TNF and clinical outcome. SUMMARY: Predicting response in Crohn's fistula patients on biologic therapy is difficult with no reliable biomarkers. This pilot study uses targeted proteomics to investigate the potential role of tissue drug levels in acting as a biomarker of treatment response.
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Enfermedad de Crohn , Fístula Rectal , Adalimumab/uso terapéutico , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/tratamiento farmacológico , Humanos , Infliximab/uso terapéutico , Proyectos Piloto , Proteómica , Fístula Rectal/tratamiento farmacológico , Fístula Rectal/etiología , Resultado del Tratamiento , Inhibidores del Factor de Necrosis Tumoral , Factor de Necrosis Tumoral alfaRESUMEN
OBJECTIVE: The study compared the risk of adenoma or carcinoma formation in the anorectal segment after either mucosectomy with manual anastomosis or stapled ileoanal anastomosis (IAA) following restorative proctocolectomy (RPC) for familial adenomatous polyposis (FAP). BACKGROUND: Few data exist on the risk of adenoma formation after either technique in FAP. METHODS: All endoscopy and histology reports for patients having RPC for FAP attending for annual pouchoscopy from 1978 to 2007 were reviewed. The incidence, timing, and histological characteristics of adenoma or carcinoma formation were recorded. RESULTS: Of the 206 patients, 140 attended for endoscopic follow-up for a median of 10.3 years after RPC. Fifty-two patients developed neoplastic transformation in the anorectal segment, with a cumulative risk at 10 years of 22.6% after mucosectomy with manual anastomosis and 51.1% after stapled IAA (P < 0.001). The median time to first adenoma was longer after mucosectomy with handsewn anastomosis than after stapled IAA (10.1 vs 6.5 years, P < 0.001). On multivariate analysis, stapled IAA (hazard ratio= 3.45, 95% confidence interval = 1.014.98) and age at RPC older than 40 years (hazard ratio = 2.20, 95% confidence interval = 1.014.89) were significantly associated with increased risk of adenoma formation. Nine patients developed a large (>10 mm) adenoma. One patient (handsewn ileoanal anastomosis) developed adenocarcinoma in the anorectal mucosa at 13 years and required pouch excision. CONCLUSIONS: Adenoma formation in the anorectal mucosa after RPC for FAP is common but carcinoma is rare. The risk is lower after mucosectomy with handsewn anastomosis than after stapled IAA. Regular endoscopic surveillance after either technique is mandatory.
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Adenoma/prevención & control , Poliposis Adenomatosa del Colon/cirugía , Mucosa Intestinal/cirugía , Proctocolectomía Restauradora , Neoplasias del Recto/prevención & control , Adenoma/etiología , Adolescente , Adulto , Anastomosis Quirúrgica/efectos adversos , Anastomosis Quirúrgica/métodos , Neoplasias del Ano/etiología , Neoplasias del Ano/prevención & control , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Proctocolectomía Restauradora/efectos adversos , Neoplasias del Recto/etiología , Riesgo , Adulto JovenRESUMEN
BACKGROUND: Patients with familial adenomatous polyposis (FAP) develop duodenal and ampullary polyps that may progress to malignancy via the adenoma-carcinoma sequence. OBJECTIVE: The aim of this study was to review a large series of FAP patients undergoing pancreaticoduodenectomy for advanced duodenal and ampullary polyposis. METHODS: A retrospective case notes review of all FAP patients undergoing pancreaticoduodenectomy for advanced duodenal and ampullary adenomatosis was performed. RESULTS: Between October 1993 and January 2010, 38 FAP patients underwent pancreaticoduodenectomy for advanced duodenal and ampullary polyps. Complications occurred in 29 patients and perioperative mortality in two. Postoperative histology revealed five patients to have preoperatively undetected cancer (R = 0.518, P < 0.001). CONCLUSIONS: Pancreaticoduodenectomy in FAP is associated with significant morbidity, but low mortality. All patients under consideration for operative intervention require careful preoperative counselling and optimization.
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Poliposis Adenomatosa del Colon/cirugía , Ampolla Hepatopancreática/cirugía , Neoplasias del Conducto Colédoco/cirugía , Neoplasias Duodenales/cirugía , Pancreaticoduodenectomía , Poliposis Adenomatosa del Colon/mortalidad , Poliposis Adenomatosa del Colon/patología , Adulto , Anciano , Ampolla Hepatopancreática/patología , Biopsia , Neoplasias del Conducto Colédoco/mortalidad , Neoplasias del Conducto Colédoco/patología , Neoplasias Duodenales/mortalidad , Neoplasias Duodenales/patología , Duodenoscopía , Femenino , Humanos , Estimación de Kaplan-Meier , Londres , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pancreaticoduodenectomía/efectos adversos , Pancreaticoduodenectomía/mortalidad , Sistema de Registros , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
OBJECTIVE: The omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) has anticolorectal cancer activity in vitro and in preclinical models. The present study tested whether a novel, enteric-coated formulation of EPA, as the free fatty acid (EPA-FFA), has chemopreventative efficacy in patients with familial adenomatous polyposis (FAP), in a randomised, double-blind, placebo-controlled trial. METHODS: Patients undergoing endoscopic surveillance of their retained rectum postcolectomy were randomised to EPA-FFA (SLA Pharma) 2 g daily or placebo for 6 months. The number and size of polyps in an area of mucosa defined by a tattoo were determined before and after intervention. Global rectal polyp burden was scored (-1, 0, +1) by examination of video endoscopy records. Mucosal fatty acid content was measured by gas chromatography-mass spectrometry. RESULTS: 55 patients with FAP were evaluated by an intention-to-treat analysis (EPA-FFA 28, placebo 27). Treatment with EPA-FFA for 6 months was associated with a mean 22.4% (95% CI 5.1% to 39.6%) reduction in polyp number (p=0.012) and a 29.8% (3.6% to 56.1%) decrease in the sum of polyp diameters (p=0.027). Global polyp burden worsened over 6 months in the placebo group (-0.34) unlike the EPA-FFA group (+0.09, difference 0.42 (0.10-0.75), p=0.011). EPA-FFA treatment led to a mean 2.6-fold increase in mucosal EPA levels (p=0.018 compared with placebo). EPA-FFA was well tolerated with an incidence of adverse events similar to placebo. CONCLUSIONS: EPA-FFA has chemopreventative efficacy in FAP, to a degree similar to that previously observed with selective cyclo-oxygenase-2 inhibitors. EPA holds promise as a colorectal cancer chemoprevention agent with a favourable safety profile.
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Poliposis Adenomatosa del Colon/prevención & control , Anticarcinógenos/uso terapéutico , Ácido Eicosapentaenoico/uso terapéutico , Pólipos Intestinales/prevención & control , Neoplasias del Recto/prevención & control , Poliposis Adenomatosa del Colon/metabolismo , Poliposis Adenomatosa del Colon/cirugía , Adolescente , Adulto , Anciano , Anticarcinógenos/efectos adversos , Colectomía , Progresión de la Enfermedad , Método Doble Ciego , Ácido Eicosapentaenoico/efectos adversos , Ácidos Grasos/metabolismo , Femenino , Humanos , Mucosa Intestinal/metabolismo , Pólipos Intestinales/metabolismo , Pólipos Intestinales/patología , Masculino , Persona de Mediana Edad , Cooperación del Paciente , Neoplasias del Recto/metabolismo , Neoplasias del Recto/patología , Sigmoidoscopía , Resultado del Tratamiento , Adulto JovenRESUMEN
INTRODUCTION: Few studies have investigated perianal fistula etiopathogenesis, and although the cryptoglandular theory is widely accepted in idiopathic cases, in Crohn's disease, it is thought to involve the interplay between microbiological, immunological and genetic factors. A pilot study was conducted to assess for metabolic variations in Crohn's perianal fistula tissue that might differ from that of idiopathic (cryptoglandular) perianal fistula tissue as a comparator. The goal was to identify any potential biomarkers of disease, which may improve the understanding of pathogenesis. AIMS AND METHODS: Fistula tract biopsies were obtained from 30 patients with idiopathic perianal fistula and 20 patients with Crohn's anal fistula. Two different assays were used in an ultra-high-performance liquid chromatography system coupled with a mass spectrometric detector to achieve broad metabolome coverage. Univariate and multivariate statistical data analyses were used to identify differentiating metabolic features corresponding to the perianal fistula phenotype (i.e. Crohn's disease vs. idiopathic). RESULTS: Significant orthogonal partial least squares discriminant analysis predictive models (validated with cross-validated-analysis of variance P value <0.05) differentiated metabolites from tissue samples from Crohn's vs. idiopathic anal fistula patients using both metabolic profiling platforms. A total of 41 metabolites were identified, suggesting alterations in pathways, including amino acid, carnitine and lipid metabolism. CONCLUSION: Metabonomics may reveal biomarkers of Crohn's perianal fistula. Further work in larger numbers is required to validate the findings of these studies as well as cross-correlation with microbiome work to better understand the impact of host-gut/environment interactions in the pathophysiology of Crohn's and idiopathic perianal fistulas and identify novel therapeutic targets.
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Enfermedad de Crohn , Fístula Rectal , Aminoácidos , Enfermedad de Crohn/diagnóstico , Humanos , Metabolismo de los Lípidos , Metabolómica , Proyectos Piloto , Fístula Rectal/diagnóstico , Fístula Rectal/etiología , Resultado del TratamientoRESUMEN
OBJECTIVE: The objective of our study was to assess the utility of MR enterography compared with capsule endoscopy for the detection of small-bowel polyps in patients with Peutz-Jeghers syndrome (PJS). SUBJECTS AND METHODS: Adult patients with PJS scheduled for surveillance capsule endoscopy were prospectively recruited and underwent MR enterography and capsule endoscopy. Polyps > 10 mm were regarded as clinically relevant. When appropriate, large polyps (> 15 mm) were removed at enteroscopy, enabling correlation with MR enterography and capsule endoscopy findings. Interobserver agreement for MR enterography and capsule endoscopy was calculated. Patient comfort, convenience, and test preference were assessed. RESULTS: Nineteen patients (median age, 39.6 years) underwent both procedures. There was no significant difference between techniques for the detection of polyps > 10 mm (18 vs 23 polyps at capsule endoscopy and MR enterography, respectively; p = 0.35) or in the number of patients in whom > 10 mm polyps were detected (eight vs 11 patients at capsule endoscopy and MR enterography, respectively; p = 0.38). However, in three patients, large polyps (> 15 mm) detected on MR enterography were not detected on capsule endoscopy; large polyps were seen in six patients at capsule endoscopy and in nine patients at MR enterography (p = 0.25). Interobserver agreement was high for MR enterography but was only fair for capsule endoscopy (kappa = 0.81 and 0.27, respectively). Size assessments of large polyps (> 15 mm) appeared more reproducible with MR enterography than with capsule endoscopy. Patients rated capsule endoscopy as more comfortable than MR enterography. There was no significant difference between the techniques with regard to patient convenience or preference. CONCLUSION: MR enterography is a promising alternative to capsule endoscopy for small-bowel surveillance in adults with PJS. Although our results suggest that capsule endoscopy is more comfortable for the patient, MR enterography may be less prone to missing large polyps and may be more reliable in their size assessment.
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Endoscopía Capsular , Pólipos Intestinales/patología , Intestino Delgado , Imagen por Resonancia Magnética/métodos , Síndrome de Peutz-Jeghers/patología , Adulto , Anciano , Femenino , Humanos , Interpretación de Imagen Asistida por Computador , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Vigilancia de la Población , Estudios Prospectivos , Sistema de Registros , Reproducibilidad de los Resultados , Método Simple Ciego , Estadísticas no Paramétricas , Encuestas y CuestionariosRESUMEN
BACKGROUND & AIMS: Most patients with familial adenomatous polyposis (FAP) develop duodenal adenomas; duodenal cancer is a major cause of mortality in this patient group. We reviewed cases of duodenal cancer in patients with FAP to identify factors that determine long-term cancer risk. METHODS: Twenty FAP patients (12 male) were identified from a registry database search. Data from registry and medical notes and endoscopic and histopathologic reports were evaluated. RESULTS: Of the cancers that developed in these patients, 11 were ampullary and 9 were duodenal. The median age at cancer diagnosis was 53 years. Seventeen patients died (median age at death, 57 y; median survival from diagnosis, 11 mo); the cause of death was metastatic or duodenal/ampullary cancer in 14 patients. Fifteen patients presented symptomatically (including 3 interval cancers while on surveillance). Two were diagnosed at surveillance and 3 were diagnosed during surgery performed for endoscopic features of advanced benign disease. Duodenal cancers were associated with a significantly lower mean colonic polyp count than ampullary cancers (496 +/- 282 vs 1322 +/- 735; P = .025); there appeared to be familial clustering of this cancer. When endoscopic data were available (n = 11 of 20), all ampullary cancers arose from ampullas greater than 1 cm. The Spigelman stage did not predict risk of ampullary cancer but did predict duodenal cancer (median stage 2 vs stage 4 for duodenal cancer). CONCLUSIONS: Once cancer arises in patients with FAP, prognosis is poor, so cancer prevention should be the main goal. Surveillance intervals should reflect both Spigelman staging and ampullary disease.
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Poliposis Adenomatosa del Colon/complicaciones , Neoplasias Duodenales/patología , Neoplasias Duodenales/fisiopatología , Adulto , Anciano , Neoplasias Duodenales/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , PronósticoRESUMEN
PURPOSE: A new sphincter-conserving treatment was evaluated in a porcine model. METHODS: A total of 36 fistulas were created by procedures that have been published previously. At fistula induction a skin biopsy was taken from which to culture fibroblasts. Four weeks after induction, when fistulas were well established, the fistula tracks were cored out. Collagen paste modified from Permacol injection (Covidien, Mansfield, MA) was then used as a solitary infill material in 11 tracks, cultured autologous fibroblasts being added to this in a further 18 tracks. The track was cored out in seven controls, but these tracks were not treated with infill material. All of the internal and external openings were closed. Anorectal excision was then carried out under terminal anesthesia at 2 to 12 weeks. Histologic examination of individual tracks was performed by an experienced pathologist. RESULTS: In this quadruped all of the infilled tracks healed, autologous fibroblasts having the best tissue integration, but only two of seven control tracks healed. CONCLUSIONS: Removal of the fistula track followed by injection of collagen healed all of the cases. The addition of autologous fibroblasts improved the histologic appearance of the tracks. A pilot study in human fistula patients is in progress.
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Fístula Rectal/cirugía , Canal Anal , Animales , Materiales Biocompatibles/administración & dosificación , Colágeno/administración & dosificación , Modelos Animales de Enfermedad , Femenino , Inyecciones Intralesiones , Fístula Rectal/patología , PorcinosRESUMEN
Germline mutations in the tumour suppressor APC cause familial adenomatous polyposis (FAP), and somatic mutations are common in sporadic colorectal cancers (CRCs). Hypermethylation of APC promoter 1A has been reported in a substantial proportion of sporadic CRCs and may cause transcriptional silencing. Methylation has been proposed as an alternative to mutation or loss of heterozygosity as a mechanism of gene inactivation. However, the significance of APC methylation has remained unclear, because it has not previously been related to the presence of mono- or bi-allelic mutations at APC. We examined 103 FAP adenomas, 11 attenuated FAP adenomas, 31 sporadic CRCs and 30 CRC cell lines, all with known germline and/or somatic APC mutations. Overall, APC promoter 1A methylation was detected in 27-45% of colorectal tumours and cell lines, but generally not in histologically normal colorectum. In contrast to previous reports, methylation was detected in similar proportions of FAP/AFAP and sporadic CRCs. Importantly, methylation was independent of the presence, number and positions of APC mutations and was not associated with the CpG island methylator phenotype. Methylation resulted in a decrease or loss of 1A isoform mRNA and reduced total APC transcript levels, although expression was retained from promoter 1B. However, neither APC protein levels, nor transcription of a panel of Wnt target genes was associated with methylation status. Our data suggest that APC promoter 1A hypermethylation may influence APC expression levels in a subtle fashion, but methylation does not result in complete gene inactivation or act as a 'second hit'.
Asunto(s)
Proteína de la Poliposis Adenomatosa del Colon/genética , Poliposis Adenomatosa del Colon/genética , Metilación de ADN , Regulación Neoplásica de la Expresión Génica , Mutación/genética , Regiones Promotoras Genéticas , Poliposis Adenomatosa del Colon/metabolismo , Proteína de la Poliposis Adenomatosa del Colon/metabolismo , Línea Celular Tumoral , Humanos , Pérdida de Heterocigocidad/genética , Imitación Molecular , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Interferente Pequeño/metabolismo , Proteínas Wnt/metabolismoRESUMEN
BACKGROUND: Perianal fistula is a topic both hard to understand and to teach. The key to understanding the treatment options and the likely success is deciphering the exact morphology of the tract(s) and the amount of sphincter involved. Our aim was to explore alternative platforms better to understand complex perianal fistulas through three-dimensional (3D) imaging and reconstruction. METHODS: Digital imaging and communications in medicine images of spectral attenuated inversion recovery magnetic resonance imaging (MRI) sequences were imported onto validated open-source segmentation software. A specialist consultant gastrointestinal radiologist performed segmentation of the fistula, internal and external sphincter. Segmented files were exported as stereolithography files. Cura (Ultimaker Cura 3.0.4) was used to prepare the files for printing on an Ultimaker 3 Extended 3D printer. Animations were created in collaboration with Touch Surgery™. RESULTS: Three examples of 3D printed models demonstrating complex perianal fistula were created. The anatomical components are displayed in different colours: red: fistula tract; green: external anal sphincter and levator plate; blue: internal anal sphincter and rectum. One of the models was created to be split in half, to display the internal opening and allow complexity in the intersphincteric space to better evaluated. An animation of MRI fistulography of a trans-sphincteric fistula tract with a cephalad extension in the intersphincteric space was also created. CONCLUSION: MRI is the reference standard for assessment of perianal fistula, defining anatomy and guiding surgery. However, communication of findings between radiologist and surgeon remains challenging. Feasibility of 3D reconstructions of complex perianal fistula is realized, with the potential to improve surgical planning, communication with patients, and augment training.
RESUMEN
BACKGROUND AND AIMS: A third of patients with Crohn's disease develop perianal fistulas. These are associated with a significant burden of symptoms and negative impact on quality of life. This study reports the use of video-assisted anal fistula treatment [VAAFT] as a means of symptom improvement; this is a minimally invasive technique to access fistula track, and diagnose/facilitate drainage of deep/complex secondary extensions with cauterization of excess inflammatory tissue. METHODS: Consecutive patients with complex Crohn's fistula undergoing VAAFT for symptomatic Crohn's anal fistula were included. They were identified from a prospectively maintained database, which was interrogated from June 2015 to November 2017. Patients underwent diagnostic fistuloscopy and fulguration of tracts/secondary extensions. Setons were sited/replaced after the procedure to maintain postoperative drainage. The primary endpoint was completion of the 'Measure your medical outcome profile' [MYMOP2] quality of life [QoL] questionnaire at 6 weeks postoperatively. Secondary outcome measures were a decisional regret scale [DRS], postoperative complications and the 30-day re-operation rate. RESULTS: Twenty-five patients underwent the procedure during the study period. In total, 21/25 patients [84%] provided MYMOP2 QoL data demonstrating a statistically significant improvement in both pain and discharge scores. Eighty-one per cent of patients who completed the questionnaire agreed/strongly agreed that the procedure was the right decision and no patient regretted undergoing the procedure. There was one re-operation but otherwise no complications. CONCLUSIONS: This study demonstrates the feasibility, safety and importantly an improvement in patient-reported outcomes in a series of patients undergoing VAAFT for complex Crohn's anal fistula. VAAFT reduces the main symptoms [pain and discharge] in patients with complex refractory anal fistulas.
Asunto(s)
Enfermedad de Crohn/complicaciones , Complicaciones Posoperatorias/epidemiología , Fístula Rectal/etiología , Fístula Rectal/cirugía , Cirugía Asistida por Video/efectos adversos , Adolescente , Adulto , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Medición de Resultados Informados por el Paciente , Calidad de Vida , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Perianal Crohn's fistula and their response to anti-tumour necrosis factor (TNF) therapies are best assessed with magnetic resonance imaging (MRI), but radiologist reporting is subjective and variable. This study investigates whether segmentation software could provide precise and reproducible objective measurements of fistula volume. METHODS: Retrospective analysis of patients with perianal Crohn's fistula at our institution between 2007 and 2013. Pre- and post-biologic MRI scans were used with varying time intervals. A total of two radiologists recorded fistula volumes, mean signal intensity and time taken to measure fistula volumes using validated Open Source segmentation software. A total of three radiologists assessed fistula response to treatment (improved, worse or unchanged) by comparing MRI scans. RESULTS: A total of 18 cases were reviewed for this pilot study. Inter-observer variability was very good for volume and mean signal intensity; intra-class correlation (ICC) 0.95 [95% confidence interval (CI) 0.91-0.98] and 0.95 (95% CI 0.90-0.97) respectively. Intra-observer variability was very good for volume and mean signal intensity; ICC 0.99 (95% CI 0.97-0.99) and 0.98 (95% CI 0.95-0.99) respectively. Average time taken to measure fistula volume was 202 s and 250 s for readers 1 and 2. Agreement between three specialist radiologists was good [kappa 0.69 (95% CI 0.49-0.90)] for the subjective assessment of fistula response. Significant association was found between objective percentage volume change and subjective consensus agreement of response (pâ=â0.001). Median volume change for improved, stable or worsening fistula response was -67% [interquartile range (IQR): -78, -47], 0% (IQR: -16, +17), and +487% (IQR: +217, +559) respectively. CONCLUSION: Quantification of fistula volumes and signal intensities is feasible and reliable, providing an objective measure of perianal Crohn's fistula and response to treatment.
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BACKGROUND: Germ-line mutations in the base-excision-repair gene MYH have been associated with recessive inheritance of multiple colorectal adenomas. Tumors from affected persons displayed excess somatic transversions of a guanine-cytosine pair to a thymine-adenine pair (G:C-->T:A) in the APC gene. METHODS: We screened for germ-line MYH mutations in 152 patients with multiple (3 to 100) colorectal adenomas and 107 APC-mutation-negative probands with classic familial adenomatous polyposis (>100 adenomas). Subgroups were analyzed for changes in the related genes MTH1 and OGG1. Adenomas were tested for somatic APC mutations. RESULTS: Six patients with multiple adenomas and eight patients with polyposis had biallelic germline MYH variants. Missense and protein-truncating mutations were found, and the spectrums of mutations were very similar in the two groups of patients. In the tumors of carriers of biallelic mutations, all somatic APC mutations were G:C-->T:A transversions. In the group with multiple adenomas, about one third of patients with more than 15 adenomas had biallelic MYH mutations. In the polyposis group, no patient with biallelic MYH mutations had severe disease (>1000 adenomas), but three had extracolonic disease. No clearly pathogenic MTH1 or OGG1 mutations were identified. CONCLUSIONS: Germ-line MYH mutations predispose persons to a recessive phenotype, multiple adenomas, or polyposis coli. For patients with about 15 or more colorectal adenomas--especially if no germ-line APC mutation has been identified and the family history is compatible with recessive inheritance--genetic testing of MYH is indicated for diagnosis and calculation of the level of risk in relatives. Clinical care of patients with biallelic MYH mutations should be similar to that of patients with classic or attenuated familial adenomatous polyposis.