Monitorización farmacocinética de terapias biológicas en enfermedad inflamatoria intestinal / Pharmacokinetic monitoring of biological therapies in inflammatory bowel disease

Objective: To analyze the activity developed by a multidisciplinary team of pharmacists, digestive specialists and clinical analysts for the therapeutic drug monitoring (TDM) of anti-TNFa therapies in inflammatory bowel disease (IBD).Methods: A prospective observational study (January-December 2019) was conducted of referrals from digestive specialists to the Clinical Pharmacokinetics Unit (CPU) of our general hospital for the TDM of anti-TNFa drugs (infliximab/adalimumab) in adults with IBD. Serum anti-TNFa concentrations were quantified in our Clinical Analysis Laboratory using lateral flow chromatography. When concentrations were undetectable, the presence of anti-drug antibodies (ADAs) was analyzed.CPU recommendations were based on the correct interpretation of anti-TNFa concentrations, therapeutic algorithms, and populational pharmacokinetic models implemented using MW-Pharm++® software. Results: Referrals were received for 84 patients (81.0% with Crohn’s disease, 8.3% with ADAs) treated with infliximab (46.4%) or adalimumab (53.6%); 64.3% were also treated with concomitant immunomodulators (IMMs). Sixty-three referrals (75.0%) were for proactive monitoring (treatment optimization) and the remainder for reactive monitoring after therapeutic failure. Anti-TNFa concentrations were subtherapeutic in 36.9% of patients, therapeutic in 39.3%, and supratherapeutic in 23.8%. Subtherapeutic/undetectable concentrations were significantly more frequent (p≤0.004) in patients treated with infliximab versus adalimumab (64.1% vs.. 13.3%) and in concomitant IMM non-adherents versus adherents (85.7% vs. 25.5%). Conclusions: Anti-TNFa TDM is frequently proactive in patients with IBD. The wide variability in anti-TNFa concentrations is in part explained by the type of anti-TNFa drug and adherence to IMM. (AU)

Objetivo: Analizar la actividad desarrollada por un equipo multidisciplinar formado por farmacéuticos, digestólogos y analistas clínicos para la monitorización farmacocinética (TDM) de terapias anti-TNFa en la enfermedad inflamatoria intestinal (EII).Métodos: Estudio observacional prospectivo (enero–diciembre 2019) de las interconsultas de TDM de anti-TNFa (infliximab/adalimumab) en pacientes adultos con EII, solicitadas por digestólogos a la Unidad de Farmacocinética Clínica (UFC) del Servicio de Farmacia de un hospital general. Las concentraciones séricas (Cs) de anti-TNFa fueron cuantificadas en el Laboratorio de Análisis Clínicos mediante cromatografía de flujo lateral. Cuando las Cs fueron indetectables, se analizó la presencia de anticuerpos anti-fármaco (AAF).La UFC realizó recomendaciones en base a la correcta interpretación de las Cs de anti-TNFa, algoritmos terapéuticos y modelos farmacocinéticos poblacionales implementados en el programa informático de ajuste bayesiano MW-Pharm++®. Resultados: Se solicitaron interconsultas para 84 pacientes (81,0% enfermedad de Crohn, 8,3% AAF positivos) con infliximab (46,4%) ó adalimumab (53,6%). 64,3% recibía otros inmunomoduladores (IMM) concomitantes. 63 interconsultas (75,0%) se relacionaron con monitorización ‘pro-activa’ (optimizar tratamiento); el resto fueron ‘re-activas’ a fallo terapéutico. Se observaron Cs de anti-TNFa subterapéuticas en 36,9% de pacientes, terapéuticas en 39,3% y supraterapéuticas en 23,8%. Las Cs subterapéuticas/indetectables fueron significativamente (p≤0,004) más frecuentes en pacientes tratados con infliximab versus adalimumab (64,1% vs. 13,3%); y en ‘no-adherentes’ versus ‘sí-adherentes’ al IMM concomitante (85,7% vs. 25,5%). Conclusiones: En estos pacientes, la TDM de anti-TNFa es frecuentemente ‘pro-activa’. Existe gran variabilidad en las Cs de anti-TNFa, explicada en parte por el fármaco anti-TNFa y la adherencia al IMM. (AU)

Usefulness of biodegradable polydioxanone stents in the treatment of postsurgical colorectal strictures and fistulas.

Benign colonic strictures and fistulas are a growing problem presenting most commonly after bowel resection. Standard treatment is with endoscopic bougies or, more usually, balloon dilation. When these approaches are not successful, other solutions are available and different endoscopic and surgical approaches have been used to treat fistulas. We present an additional option--biodegradable stents--for the treatment of colonic strictures and fistulas that have proven refractory to other endoscopic interventions. We analyzed the results from 10 patients with either a postsurgical colorectal stricture (n =7) or rectocutaneous fistula (n =3) treated with the biodegradable SX-ELLA esophageal stent (covered or uncovered). Stents were successfully placed in nine patients, although early migration subsequently occurred in one. Placement was impossible in one patient due to deformity of the area and the fact that the stricture was approximately 30cm from the anus. The fistulas were successfully closed in all patients, although symptoms reappeared in one patient. In the six patients who received stents for strictures, symptoms resolved in five; in the remaining patient, the stent migrated shortly after the endoscopy. Treatment of colonic strictures and rectocutaneous fistulas with biodegradable stents is an effective alternative in the short-to-medium term. The stent does not have to be removed and is subject to very few complications. The drawbacks of this approach are the need to repeat the procedure in some patients and the lack of published series on efficacy.

Efficacy of pediatric colonoscopy used as push enteroscopy in the management of capsule endoscopy findings.

BACKGROUND: recent advances in endoscopy have enabled us to explore the small intestine more efficiently, both with capsule endoscopy and double-balloon enteroscopy. However, these methods are not available in all hospitals. Therefore, when capsule endoscopy reveals proximal jejunal lesions, a possible alternative for treatment could involve push enteroscopy combined with colonoscopy. Lesions can thus be marked for subsequent monitoring. OBJECTIVES: to describe the efficacy of pediatric colonoscopy for diagnosis, the marking of the area explored, and therapeutic options. MATERIAL AND METHODS: between October 2007 and September 2008 a total of 21 enteroscopies were performed using a pediatric colonoscope. Nine of these were used to take jejunal biopsy samples due to suspected disease of the mucosa. In 10 of the remaining 12, capsule endoscopy revealed lesions (vascular malformations or jejunal bleeding), and in 2 intestinal transit time was analyzed due to suspected jejunal stenosis. We used a PENTAX EC-3470-LK pediatric colonoscope, whose 11.6-mm sectional diameter and 3.8-mm working channel make it possible to administer all the usual endoscopic treatments. RESULTS: therapeutic endoscopy was performed on 7 men and 5 women (mean age 63.3 years). Jejunal lesions were observed in 10 cases (5 cases of angiodysplasia, 2 cases of jejunal stenosis, 1 case of nonmalignant thickened jejunal folds, 1 eroded submucosal tumor, and 1 case of duodenal and jejunal varices). The most distal area was marked with India ink (2), hemoclips (4), or both to help locate the lesions using simple abdominal radiography or capsule endoscopy. CONCLUSIONS: jejunal enteroscopy enabled a firm diagnosis to be made in most of the patients studied. We were able to treat 58% of patients and mark the areas explored for subsequent follow-up. With hemoclips we were able to locate the most distal point explored using simple abdominal radiography.

Eficacia del colonoscopio pediátrico como enteroscopio de pulsión en el manejo de los hallazgos de la cápsula endoscópica / Efficacy of pediatric colonoscopy used as push enteroscopy in the management of capsule endoscopy findings

Introducción: los recientes avances en endoscopia nos hanpermitido explorar de una forma más eficaz el intestino delgado,tanto con la cápsula endoscópica (CE) como con enteroscopia dedoble balón. El problema que aparece es la no disponibilidad deestos dos métodos en todos los hospitales. Por ello, cuando se venlesiones en la CE, una alternativa posible para el tratamiento delas lesiones de yeyuno proximal podría ser la realización de unaenteroscopia de pulsión con colonoscopio con fines terapéuticosy de marcaje para control de las lesiones.Objetivos: describir la eficacia del colonoscopio pediátrico encuanto al diagnóstico, señalización de zona explorada y posibilidadesterapéuticas.Material y métodos: durante el periodo comprendido entreoctubre de 2007 y septiembre de 2008, se han realizado 21 enteroscopiascon colonoscopio pediátrico, de las cuales 9 eran paratomar biopsias yeyunales por sospecha de patología mucosa. Delas otras 12, en 10 se vieron lesiones por la cápsula endoscópica(malformaciones vasculares o sangrado yeyunal) y en 2 se hizotránsito intestinal sospecha de estenosis yeyunal.Se utilizó un colonoscopio pediátrico PENTAX EC-3470-LKque presenta un diámetro de sección de 11,6 mm y un canal detrabajo de 3,8 mm, lo cual nos permite realizar cualquier tipo detratamiento endoscópico habitual.Resultados: se hizo enteroscopia con fines terapéuticos en7 hombres y 5 mujeres, con una edad media de 63,3 años. Sevieron lesiones endoscópicas en yeyuno en diez casos: 5 angiodisplasias,2 estenosis yeyunales, uno con pliegues engrosados yeyunalescon histología normal, un tumor submucoso erosionado yun caso de varices duodenales y yeyunales.En los últimos pacientes se hizo marcaje de la zona más distalexplorada con tinta china (2) o con hemoclips (4) o con ambos,para ayudar a localizar topográficamente las lesiones mediante radiologíasimple de abdomen o cápsula endoscópica...(AU)

Background: recent advances in endoscopy have enabled us toexplore the small intestine more efficiently, both with capsule endoscopyand double-balloon enteroscopy. However, these methodsare not available in all hospitals. Therefore, when capsule endoscopyreveals proximal jejunal lesions, a possible alternative for treatmentcould involve push enteroscopy combined with colonoscopy. Lesionscan thus be marked for subsequent monitoring.Objectives: to describe the efficacy of pediatric colonoscopyfor diagnosis, the marking of the area explored, and therapeuticoptions.Material and methods: between October 2007 and September2008 a total of 21 enteroscopies were performed using apediatric colonoscope. Nine of these were used to take jejunalbiopsy samples due to suspected disease of the mucosa. In 10 ofthe remaining 12, capsule endoscopy revealed lesions (vascularmalformations or jejunal bleeding), and in 2 intestinal transit timewas analyzed due to suspected jejunal stenosis. We used a PENTAXEC-3470-LK pediatric colonoscope, whose 11.6-mm sectionaldiameter and 3.8-mm working channel make it possible toadminister all the usual endoscopic treatments.Results: therapeutic endoscopy was performed on 7 men and5 women (mean age 63.3 years). Jejunal lesions were observed in10 cases (5 cases of angiodysplasia, 2 cases of jejunal stenosis, 1case of nonmalignant thickened jejunal folds, 1 eroded submucosaltumor, and 1 case of duodenal and jejunal varices). The mostdistal area was marked with India ink (2), hemoclips (4), or both tohelp locate the lesions using simple abdominal radiography orcapsule endoscopy.Conclusions: jejunal enteroscopy enabled a firm diagnosis tobe made in most of the patients studied. We were able to treat58% of patients and mark the areas explored for subsequent follow-up. With hemoclips we were able to locate the most distalpoint explored using simple abdominal radiography(AU)

Endoscopic resection of large colorectal polyps.

BACKGROUND: Endoscopic polypectomy is a common technique, but there are discrepancies over which treatment--surgical or endoscopic--to follow in case of polyps of 2 cm or larger. OBJECTIVES: To analyse the efficacy and complications of colonoscopic polypectomy of large colorectal polyps. PATIENTS AND METHODS: 147 polypectomies were performed on 142 patients over an eight-year period. The technique used was that of submucosal adrenaline 1:10000 or saline injection at the base of the polyp, followed by resection of the polyp using a diathermic snare in the smallest number of fragments. Remnant adenomatous tissue was fulgurated with an argon plasma coagulator. Lately, prophylactic hemoclips have been used for thick-pedicle polyps. Complete removal was defined as when a polyp was completely resected in one or more polypectomy sessions. Polypectomy failure was defined as when a polyp could not be completely resected or contained an invasive carcinoma. RESULTS: The mean patient age was 67.9 years (range, 4-90 years), with 68 men and 79 women. There were 74 sessile polyps, and the most common location was the sigmoid colon. The most frequent histology was tubulovillous. Most of the polyps (96.6%), were resected and cured. This was not achieved in four cases of invasive carcinoma, and a villous polyp of the cecum. All pedunculated polyps were resected in one session, whereas the average number of colonoscopies for sessile polyps was 1.35 +/- 0.6 (range, 1-4). The polypectomy was curative in all of the in situ carcinomata except one. As for complications, 2 colonic perforations (requiring surgery) and 8 hemorrhages appeared, which were controlled via endoscopy. There was no associated mortality. CONCLUSIONS: Endoscopic polypectomy of large polyps (> or =2 cm) is a safe, effective treatment, though it is not free from complications. Complete resection is achieved in a high percentage, and there are few relapses. It should be considered a technique of choice for this type of polyp, except in cases of invasive carcinoma.

[The treatment of anal fissure with botulinum toxin]. / Tratamiento de la fisura anal con toxina botulínica.

BACKGROUND: The use of botulinic toxin has led to new perspectives in the treatment of anal fissures. However, the most effective dose, length of treatment and long term results require further studies to determine the most appropriate place for this therapy. PATIENTS AND METHODS: A prospective study was carried out in 40 consecutive patients diagnosed with anal fissure of more than 3 months in duration. Fifteen U of botulinic toxin were injected in the external anal sphincter and the evolution was studied over 6 months. The patients completed a pain scale designed for the study after 1 week, and 1, 3 and 6 months after the injection. The degree of pain, healing and need for surgery were evaluated during the follow up. RESULTS: Healing occurred in 17 patients after 3 months (42.5%) and after 6 months in 3 more patients (50%). Eight patients required surgery during follow up (20%). In the remaining patients, the pain significantly decreased allowing conservative management. Only 2 patients demonstrated incontinence for slight, transitory gases (5%). CONCLUSIONS: Injection of botulinic toxin is well tolerated and is relatively effective as an alternative in the treatment of anal fissure. Most patients respond in the first days after treatment and the effect persists for at least 6 months. The use of doses higher than those used in this study merits further studies.

[Hepatic granulomas in a patient with acquired hypogammaglobulinemia]. / Granulomas hepáticos en una paciente con hipogammaglobulinemia adquirida.

The case of a young female diagnosed with an IgG deficit and hepatic granulomas is presented. After 6 years of follow up the patient remains asymptomatic without treatment and with moderate biochemical cholestasis. The tests performed did not lead to a definitive etiologic diagnosis, therefore, according to a review of the literature, we believe that the granulomatous reactions are related with the hypogammaglobulinemia itself.

[Recombinant alfa-2 interferon treatment of a patient with chronic hepatitis B and ulcerative colitis]. / Tratamiento con interferón alfa-2 recombinante en un paciente con hepatitis crónica por virus B y colitis ulcerosa.

The case of a patient ulcerative colitis involving an autoimmune base who was treated with recombinant alpha-2 interferon for concomitantly presenting chronic hepatitis B in the replicative phase is reported. With this therapy unreplicative seroconversion of the disease was achieved without modification of the course of the chronic inflammatory intestinal disease (CIID) during treatment or over the posttreatment follow up period. A brief review of the literature was performed concerning the role of autoimmunity in ulcerative colitis, treatment with alpha-interferon in chronic hepatitis B and the exacerbation of autoimmune phenomena which may lead to interferon treatment. According to the evolution of this case and the review of the literature, the authors conclude that the existence of CIID does not contra-indicate the use of recombinant alpha-2 interferon in patients with chronic viral hepatitis, although special control of the disease should be carried out during the treatment period.

[Solitary ulcer of the rectum and granulomatous appendicitis, a casual association?]. / Ulcera solitaria de recto y apendicitis granulomatosa, una asociación casual?

We report a case of solitary rectal ulcer (SRU) in a patient who had been previously diagnosed of granulomatous appendicitis. Both entities were histologically confirmed. The patient is asymptomatic after appendectomy done one and a half years ago, demonstrating the low recurrence rate of granulomatous appendicitis and the silent course of solitary rectal ulcer in many patients. Both entities may be related.