Addition of Platelet-Rich Plasma to Endorectal Advancement Flap Repair Does Not Enhance the Healing of Cryptoglandular Transsphincteric Fistulas.

BACKGROUND: Endorectal advancement flap repair is often performed for the treatment of cryptoglandular transsphincteric fistulas. However, this procedure fails in approximately 1 of 4 patients. Based on its supposed healing properties, platelet-rich plasma might enhance the outcome of this procedure. OBJECTIVE: To evaluate and compare the short-term and long-term outcomes after endorectal advancement flap repair with and without platelet-rich plasma injection in patients with a cryptoglandular transsphincteric fistula. DESIGN: Retrospective cohort study. SETTING: Tertiary referral hospital for proctology in the Netherlands. PATIENTS: Consecutive patients with a cryptoglandular transsphincteric fistula. Inverse propensity score-weighted comparison was used to adjust for confounding and selection bias. INTERVENTIONS: Endorectal advancement flap repair with and without platelet-rich plasma injection. MAIN OUTCOME MEASURES: Clinical fistula closure within 1 year without need for a reintervention (primary healing), clinical fistula closure within 1 year corrected for reinterventions (secondary healing), overall fistula healing within 1 year, and long-term outcomes assessed by a questionnaire. RESULTS: In total, 219 patients underwent an endorectal advancement flap repair. In 88 patients (40.2%), platelet-rich plasma was injected. No significant difference was observed in primary healing (67.0% vs 69.5%, p = 0.71), secondary healing (37.5% vs 43.5%, p = 0.60), or overall healing (73.9% vs 77.1%, p = 0.58) between patients treated with and without platelet-rich plasma injection. Long-term follow-up was available in 67.1% of the patients with a mean follow-up of 6.8 years (SD: 3.7 years). Among all patients who reached fistula healing, whether primary or secondary, within 1 year and had available long-term follow-up data, recurrence rates were also not significantly different (6.3% vs 2.9%, p = 0.37). Propensity score-weighted analysis showed that patients treated with a platelet-rich plasma injection were not more likely to achieve primary healing (OR 1.0; 95% CI, 0.5-1.9), secondary healing (OR 1.1; 95% CI, 0.2-3.2), overall healing (OR 0.9; 95% CI, 0.5-1.7), or recurrence at long-term follow-up (OR 1.1; 95% CI, 0.4-18.8) compared with patients without platelet-rich plasma injection. LIMITATIONS: Retrospective design, lack of postoperative imaging, and assessment of long-term follow-up using a questionnaire. CONCLUSION: Addition of platelet-rich plasma injection does not improve the short-term and long-term outcomes of endorectal advancement flap repair in patients with a cryptoglandular transsphincteric fistula treated in a tertiary referral center. See Video Abstract . ADICIN DE PLASMA RICO EN PLAQUETAS A LA REPARACIN DEL COLGAJO DE AVANCE ENDORRECTAL NO MEJORA LA CURACIN DE LAS FSTULAS TRANSESFINTERIANAS CRIPTOGLANDULARES: ANTECEDENTES:La reparación con colgajo de avance endorrectal a menudo se realiza para el tratamiento de fístulas transesfinterianas criptoglandulares. Sin embargo, este procedimiento falla en aproximadamente uno de cada cuatro pacientes. Basándose en sus supuestas propiedades curativas, el plasma rico en plaquetas (PRP) podría mejorar el resultado de este procedimiento.OBJETIVO:Evaluar y comparar los resultados a corto y largo plazo después de la reparación con colgajo de avance endorrectal con y sin inyección de PRP en pacientes con una fístula transesfintérica criptoglandular.DISEÑO:Estudio de cohorte retrospectivo.ÁMBITO:Hospital terciario de referencia para proctología en los Países Bajos.PACIENTES:Pacientes consecutivos con fístula transesfintérica criptoglandular. Se utilizó una comparación ponderada por puntuación de propensión inversa para ajustar los factores de confusión y el sesgo de selección.INTERVENCIONES:Reparación del colgajo de avance endorrectal con y sin inyección de PRP.PRINCIPALES MEDIDAS DE VALORACIÓN:Cierre clínico de la fístula dentro de un año sin necesidad de reintervención (cicatrización primaria), cierre clínico de la fístula dentro de un año corregido por reintervenciones (cicatrización secundaria), curación general de la fístula dentro de un año y resultados a largo plazo evaluados mediante un cuestionario.RESULTADOS:En total, 219 pacientes se sometieron a una reparación con colgajo de avance endorrectal. En 88 pacientes (40,2%) se inyectó PRP. No se observaron diferencias significativas en la curación primaria (67,0% frente a 69,5%, p = 0,71), curación secundaria (37,5% frente a 43,5%, p = 0,60) y curación general (73,9% frente a 77,1%, p = 0,58).) entre pacientes con y sin inyección de PRP, respectivamente. El seguimiento a largo plazo estuvo disponible en el 67,1% de los pacientes con un seguimiento medio de 6,8 años (desviación estándar: 3,7 años). Dentro de todos los pacientes que alcanzaron la curación de la fístula, tanto primaria como secundaria, dentro de un año y tenían datos de seguimiento a largo plazo disponibles, las tasas de recurrencia tampoco fueron significativamente diferentes (6,3% vs. 2,9%, p = 0,37). El análisis ponderado por puntuación de propensión mostró que los pacientes tratados con una inyección de PRP no tenían más probabilidades de lograr la curación primaria (odds ratio [OR] 1,0; intervalo de confianza [IC] del 95 %: 0,5 - 1,9), curación secundaria (OR 1,1; IC del 95 % 0,2 - 3,2), curación general (OR 0,9; IC 95 % 0,5 - 1,7) o recurrencia en el seguimiento a largo plazo (OR 1,1; IC 95 % 0,4 - 18,8) en comparación con pacientes sin inyección de PRP.LIMITACIONES:Diseño retrospectivo, falta de imágenes postoperatorias y evaluación del seguimiento a largo plazo mediante un cuestionario.CONCLUSIÓN:La adición de la inyección de PRP no mejora el resultado a corto y largo plazo de la reparación con colgajo de avance endorrectal en pacientes con una fístula transesfintérica criptoglandular tratados en un centro de referencia terciario. (Traducción- Dr. Ingrid Melo ).

Impact of timing of primary ileocecal resection on prognosis in patients with Crohn's disease.

BACKGROUND: The advantage of early ileocecal resection after Crohn's disease diagnosis is a matter of debate. This study aims to assess the timing of ileocecal resection on prognosis, after correction for possible confounders. METHODS: Patients with Crohn's disease with primary ileocecal resection between 2000 and 2019 were included in a retrospective multicentre cohort. The primary endpoint was endoscopic recurrence (Rutgeerts score ≥i2b) within 18 months. Secondary endpoints were escalation of inflammatory bowel disease medication within 18 months and re-resection during follow-up. The association between timing of ileocecal resection and these endpoints was investigated using multivariable proportional hazard models, corrected for covariates including Montreal classification, postoperative prophylaxis, smoking, indication for surgery, medication before ileocecal resection, perianal fistulas, surgical approach, histology, length of resected segment and calendar year. RESULTS: In 822 patients ileocecal resection was performed after a median of 3.1 years (i.q.r. 0.7-8.0) after Crohn's disease diagnosis. The lowest incidence of endoscopic recurrence, escalation of inflammatory bowel disease medication and re-resection was observed for patients undergoing ileocecal resection shortly after diagnosis (0-1 months). After correction for covariates, patients with ileocecal resection at 0, 4 and 12 months after diagnosis had a cumulative incidence of 35 per cent, 48 per cent and 39 per cent for endoscopic recurrence, 20 per cent, 29 per cent and 28 per cent for escalation of inflammatory bowel disease medication and 20 per cent, 30 per cent and 34 per cent for re-resection, respectively. In the multivariable model ileocolonic disease (HR 1.39 (95 per cent c.i. 1.05 to 1.86)), microscopic inflammation of proximal and distal resection margins (HR 2.20 (95 per cent c.i. 1.21 to 3.87)) and postoperative prophylactic biological and immunomodulator (HR 0.16 (95 per cent c.i. 0.05 to 0.43)) were associated with endoscopic recurrence. CONCLUSION: The timing of ileocecal resection was not associated with a change of disease course; in the multivariable model, the postoperative recurrence was not affected by timing of ileocecal resection.

Stromal vascular fraction with platelet-rich plasma injection during surgery is feasible and safe in treatment-refractory perianal fistulising Crohn's disease: A pilot study.

BACKGROUND: An unmet need remains for improved management in perianal fistulising Crohn's disease (pCD). Recently, local administration of adipose-derived cells has shown promising results. AIMS: To assess the safety and feasibility of injection of stromal vascular fraction (SVF) with platelet-rich plasma (PRP) in patients with pCD. METHODS: Patients ≥ 18 years with pCD were included and underwent fistula curettage, SVF with PRP injection, and closure of the internal opening. The primary endpoint was safety at 12 months. The secondary outcomes were complete radiological healing at 3 months (absence of fluid-containing tracts on MRI) and partial and complete clinical response at 3 and 12 months (closure of ≥1, respectively, all treated external opening(s)). RESULTS: Twenty-five patients were included (35 [IQR 25-40] years; 14 [56%] female); median CD duration 4 [IQR 2-8] years. Twenty-four (95%) patients had previously undergone fistula surgery. No adverse events were encountered at lipoharvesting sites. Two (8%) patients were readmitted to hospital and six (24%) underwent unplanned re-interventions. Post-operative MRI (n = 24) showed complete radiological healing in nine (37.5%) patients. Partial clinical response was present in 48% (12/25) at 3 months and in 68% (17/25) at 12 months, and complete clinical closure in five (20%) patients at 3 months and in 10 (40%) patients at 12 months. CONCLUSION: Injection with autologous SVF with PRP is feasible and safe in patients with treatment-refractory pCD. Early complete radiological healing was observed in more than one-third of patients, and clinical response in two-thirds of patients at 12 months.

Prophylactic Medication for the Prevention of Endoscopic Recurrence in Crohn's Disease: a Prospective Study Based on Clinical Risk Stratification.

BACKGROUND: To prevent recurrence after ileocolonic resection [ICR] in Crohn's disease [CD], postoperative prophylaxis based on risk stratification is recommended in international guidelines. This study aimed to evaluate postoperative CD recurrence after implementation of a clinical management algorithm and to determine the predictive value of clinical and histological risk factors [RFs]. METHODS: In this multicentre, prospective cohort study, CD patients [≥16 years] scheduled for ICR were included. The algorithm advised no postoperative medication for low-risk patients, and treatment with prophylaxis [immunosuppressant/biological] for high-risk patients [≥1 RF: active smoking, penetrating disease, prior ICR]. Clinical and histological RFs [active inflammation, granulomas, plexitis in resection margins] for endoscopic recurrence [Rutgeerts' score ≥i2b at 6 months] were assessed using logistic regression and ROC curves based on predicted probabilities. RESULTS: In total, 213 CD patients after ICR were included [age 34.5 years; 65% women] (93 [44%] low-risk; 120 [56%] high-risk: 45 [38%] smoking; 51 [43%] penetrating disease; 51 [43%] prior ICR). Adherence to the algorithm was 82% in low-risk [no prophylaxis] and 51% in high-risk patients [prophylaxis]. Endoscopic recurrence was higher in patients treated without prophylaxis than with prophylaxis in both low [45% vs 16%, p = 0.012] and high-risk patients [49% vs 26%, p = 0.019]. Clinical risk stratification including the prescription of prophylaxis corresponded to an area under the curve [AUC] of 0.70 (95% confidence interval [CI] 0.61-0.79). Clinical RFs combined with histological RFs increased the AUC to 0.73 [95% CI 0.64-0.81]. CONCLUSION: Adherence to this management algorithm is 65%. Prophylactic medication after ICR prevents endoscopic recurrence in low- and high-risk patients. Clinical risk stratification has an acceptable predictive value, but further refinement is needed.

Indications, Postoperative Management, and Long-term Prognosis of Crohn's Disease After Ileocecal Resection: A Multicenter Study Comparing the East and West.

BACKGROUND: The Crohn's disease (CD) phenotype differs between Asian and Western countries and may affect disease management, including decisions on surgery. This study aimed to compare the indications, postoperative management, and long-term prognosis after ileocecal resection (ICR) in Hong Kong (HK) and the Netherlands (NL). METHODS: CD patients with primary ICR between 2000 and 2019 were included. The endpoints were endoscopic (Rutgeerts score ≥i2b and/or radiologic recurrence), clinical (start or switch of inflammatory bowel disease medication), and surgical recurrences. Cumulative incidences of recurrence were estimated with a Bayesian multivariable proportional hazards model. RESULTS: Eighty HK and 822 NL patients were included. The most common indication for ICR was penetrating disease (HK: 32.5%, NL: 22.5%) in HK vs stricturing disease (HK: 32.5%, NL: 48.8%) in the NL (P < .001). Postoperative prophylaxis was prescribed to 65 (81.3%) HK patients (28 [35.0%] aminosalicylates [5-aminosalicylic acid]; 30 [37.5%] immunomodulators; 0 biologicals) vs 388 (47.1%) NL patients (67 [8.2%] 5-aminosalicylic acid; 187 [22.8%] immunomodulators; 69 [8.4%] biologicals; 50 [6.1%] combination therapy) (P < .001). Endoscopic or radiologic evaluation within 18 months was performed in 36.3% HK vs 64.1% NL (P < .001) patients. No differences between both populations were observed for endoscopic (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.24-1.21), clinical (HR, 0.91; 95% CI, 0.62-1.32), or surgical (HR, 0.61; 95% CI, 0.31-1.13) recurrence risks. CONCLUSION: The main indication for ICR in CD patients is penetrating disease in HK patients and stricturing disease in NL patients. Although considerable pre- and postoperative management differences were observed between the two geographical areas, the long-term prognosis after ICR is similar.

This is the first study reporting similar long-term prognoses after ileocecal resection in Crohn's disease in low- and high-incidence countries despite differences in Crohn's disease phenotype at diagnosis, surgical approach, indications, and pre- and postoperative management including prophylactic medication.

Risk Prediction and Comparative Efficacy of Anti-TNF vs Thiopurines, for Preventing Postoperative Recurrence in Crohn's Disease: A Pooled Analysis of 6 Trials.

BACKGROUND & AIMS: The superiority of anti-TNF-α agents to thiopurines for the prevention of postoperative recurrence of Crohn's disease (CD) after ileocolonic resection remains controversial. In this meta-analysis of individual participant data (IPD), the effect of both strategies was compared and assessed after risk stratification. METHODS: After a systematic literature search, IPD were requested from randomized controlled trials investigating thiopurines and/or anti-TNF-α agents after ileocolonic resection. Primary outcome was endoscopic recurrence (ER) (Rutgeerts score ≥i2) and secondary outcomes were clinical recurrence (Harvey-Bradshaw Index/Crohn's Disease Activity Index score) and severe ER (Rutgeerts score ≥i3). A fixed effect network meta-analysis was performed. Subgroup effects were assessed and a prediction model was established using Poisson regression models, including sex, smoking, Montreal classification, CD duration, history of prior resection and previous exposure to anti-TNF-α or thiopurines. RESULTS: In the meta-analysis of IPD, 645 participants from 6 studies were included. In the total population, a superior effect was demonstrated for anti-TNF-α compared with thiopurine prophylaxis for ER (relative risk [RR], 0.52; 95% confidence interval [CI], 0.33-0.80), clinical recurrence (RR, 0.50; 95% CI, 0.26-0.96), and severe ER (RR, 0.41; 95% CI, 0.21-0.79). No differential subgroup effects were found for ER. In Poisson regression analysis, previous exposure to anti-TNF-α and penetrating disease behavior were associated with ER risk. The advantage of anti-TNF-α agents as compared with thiopurines was observed in low- and high-risk groups. CONCLUSIONS: Anti-TNF-α is superior to thiopurine prophylaxis for the prevention of endoscopic and clinical postoperative CD recurrence after ileocolonic resection. The advantage of anti-TNF-α agents was confirmed in subgroup analysis and after risk stratification.