Suboptimal response to tumor necrosis factor antagonists in inflammatory bowel disease in Latin America: EXPLORE LATAM study.

OBJECTIVE: Data on anti-tumor necrosis factor (anti-TNF) treatment and suboptimal response (SOR) among patients with inflammatory bowel diseases (IBD) in Latin America (LATAM) are scarce. This study evaluated the incidence and indicators of SOR to anti-TNF therapy in patients with ulcerative colitis (UC) and Crohn's disease (CD) from Argentina, Colombia and Mexico. PATIENTS AND METHODS: We performed retrospective analysis of data from LATAM patients of the EXPLORE study (NCT03090139) including adult patients with IBD who initiated anti-TNF therapy between March 2010 to March 2015. The cumulative incidence of SOR to first-line anti-TNF therapy was assessed. A physician survey to assess barriers to anti-TNF therapies was also carried out. RESULTS: We included 185 IBD patients (UC/CD: 99/86) treated with first-line anti-TNF from Argentina (38 UC; 40 CD), Colombia (21 UC; 25 CD) and Mexico (40 UC; 21 CD). 36.4% of patients with UC and 46.5% of patients with CD experienced SOR to anti-TNF therapy during the median (interquartile range) observational period: 49.0 months (37.2-60.1) in UC, and 50.0 months (40.9-60.1) in CD. The most common indicator of SOR among patients was augmentation of non-biologic therapy (UC: 41.7%; CD: 35.0%). Affordability and late referral to IBD specialist care centers were the most common barriers to anti-TNF therapies. CONCLUSIONS: SOR to anti-TNF therapy was common in LATAM IBD patients, where augmentation with non-biologic therapy represented the most frequent indicator of SOR across indications. Our findings contribute to the current evidence on the unmet needs associated with anti-TNF in LATAM.

Latin America consensus statement inflammatory bowel disease: importance of timely access to diagnosis and treatment.

Background: Inflammatory bowel diseases (IBDs) are chronic conditions that negatively interferes with the quality of life of the patients, on a physical, emotional, and social level. Its symptoms can vary including diarrhea, bleeding, abdominal pain, fever, and weight loss, depending on the type and location and severity of the disease. Despite evolving treatment, they do not always achieve control of the symptoms, so between 23% and 45% of people with idiopathic chronic ulcerative colitis, and up to 75% of those with Crohn's disease, eventually, will need surgery. Objective: The increase in its incidence in Latin America has promoted a renewed interest on the part of the medical and scientific community in standardizing and unifying criteria for the proper diagnosis and management of the disease, which is part of the current discussions of various events; however, this interest has not yet been reflected in policies and initiatives by governments to address the disease. We decided to develop a consensus meeting in order to elucidate the actual situation of IBD care in our region. Design: The methodology employed to build the consensus document derived from a review of literature, evidence, and policies on IBD, followed by a process of validation and feedback with a group of 10 experts in the field. Methods: Nine experts from different countries in Latin America were reunited in web meetings on 2 days and voted on topics derived from the consensus document. A full agreement with 100% approval was needed, so topics were discussed to reach the consensus otherwise were removed. Results: There is still a lack of information about IBD in Latin America, therefore IBD continues to be an 'invisible' disease and is little recognized by decision-makers. Conclusion: This document describes the current situation of IBDs in the Latin American region, highlighting the main barriers and challenges in timely access to diagnosis and treatment, in order to demonstrate the need to promote the development and implementation of policies, in order to improve the quality of care of patients with IBD.

Epidemiology of inflammatory bowel disease in Mexico and Colombia: Analysis of health databases, mathematical modelling and a case-series study.

BACKGROUND AND AIMS: Ulcerative Colitis (UC) and Crohn's Disease (CD) have a major impact on quality of life and medical costs. The aim of the study was to estimate the prevalence, incidence and clinical phenotypes of Inflammatory Bowel Disease (IBD) cases in Mexico and Colombia. METHODS: We analyzed official administrative and health databases, used mathematical modelling to estimate the incidence and complete prevalence, and performed a case-series of IBD patients at a referral center both in Mexico and Colombia. RESULTS: The age-adjusted complete prevalence of UC per 100,000 inhabitants for 2015/2016 ranged from 15.65 to 71.19 in Mexico and from 27.40 to 69.97 in Colombia depending on the model considered. The prevalence of CD per 100,000 inhabitants in Mexico ranged from 15.45 to 18.08 and from 16.75 to 18.43 in Colombia. In Mexico, the age-adjusted incidence of UC per 100,000 inhabitants per year ranged from 0.90 to 2.30, and from 0.55 to 2.33 in Colombia. The incidence for CD in Mexico ranged from 0.35 to 0.66 whereas in Colombia, the age-adjusted incidence of CD ranged from 0.30 to 0.57. The case-series included 200 IBD patients from Mexico and 204 patients from Colombia. The UC/CD prevalence ratio in Mexico and Colombia was 1.50:1 and 4.5:1 respectively. In Mexico, the female/male prevalence ratio for UC was 1.50:1 and 1.28:1 for CD, while in Colombia this ratio was 0.68:1 for UC and 0.8:1 for CD. In Mexico the relapse rate for UC was 63.3% and 72.5% for CD, while those rates in Colombia were 58.2% for UC and 58.3% for CD. CONCLUSIONS: The estimated burden of disease of IBD in Mexico and Colombia is not negligible. Although these findings need to be confirmed by population-based studies, they are useful for decision-makers, practitioners and patients with this condition.

[Pneumatosis cystoides intestinalis: a case report and review of the literature]. / Pneumatosis quística intestinalis: presentación de un caso y revisión de la literatura.

Pneumatosis cystoides intestinalis features the presence of subserum or submucous cysts with gas in the intestinal wall. Its prevalence is 0.03%, although it has increased in the past decades due to a greater use of colonoscopy in everyday medical practice. Though there are several theories about its origin and many associated diseases were reported, its pathogenesis still remains uncertain. It is generally diagnosed as a finding in an imaging test. The treatment depends on the severity of the associated disease and symptoms. We report the case of a 59-year-old woman, heavy smoker, with no other clinical conditions who took a medical consultation due to abdominal bloating. She underwent a screening colonoscopy which detected the existence of cysts on the colonic wall. Afterwards, a computed tomography was performed and showed apical lung bullae, gas in a colonic wall segment, and ascitis associated to a big anexial tumor. She underwent a cytoreductive surgery, confirming the presence of advanced ovary neoplasm. The endoscopic biopsy confirmed the diagnosis of penumatosis cystoides intestinalis. We report these case because it is a rare entity which requires uncommon management and treatment guidelines.

Pneumatosis quística intestinalis: presentación de un caso y revisión de la literatura / [Pneumatosis cystoides intestinalis: a case report and review of the literature].

Pneumatosis cystoides intestinalis features the presence of subserum or submucous cysts with gas in the intestinal wall. Its prevalence is 0.03

, although it has increased in the past decades due to a greater use of colonoscopy in everyday medical practice. Though there are several theories about its origin and many associated diseases were reported, its pathogenesis still remains uncertain. It is generally diagnosed as a finding in an imaging test. The treatment depends on the severity of the associated disease and symptoms. We report the case of a 59-year-old woman, heavy smoker, with no other clinical conditions who took a medical consultation due to abdominal bloating. She underwent a screening colonoscopy which detected the existence of cysts on the colonic wall. Afterwards, a computed tomography was performed and showed apical lung bullae, gas in a colonic wall segment, and ascitis associated to a big anexial tumor. She underwent a cytoreductive surgery, confirming the presence of advanced ovary neoplasm. The endoscopic biopsy confirmed the diagnosis of penumatosis cystoides intestinalis. We report these case because it is a rare entity which requires uncommon management and treatment guidelines.

Risk of colorectal neoplasia in patients with celiac disease: a multicenter study.

BACKGROUND AND AIMS: The association of celiac disease with colorectal neoplasia is controversial. The aim of this study was to determine the risk of colorectal neoplasia among patients with celiac disease. METHODS: We carried out a multicenter, retrospective case-control study, within four community hospitals. Celiac disease patients with a complete colonoscopy were regarded as cases and those without celiac disease as controls. For each case, two controls matched for age, sex, indication for colonoscopy and colorectal cancer family history, were randomly selected. The main outcome evaluated was risk of colorectal polyps, adenomas, advanced neoplastic lesions and cancer. RESULTS: We identified 118 patients with celiac disease and 236 controls. The risk of polyps, adenomas and advanced neoplastic lesions was similar in both groups (OR 1.25, CI 0.71-2.18, p=0.40; OR 1.39, CI 0.73-2.63, p=0.31; and OR 1.00, CI 0.26-3.72, p=1.00, respectively). On multivariate analysis, age >75 years old, and first-grade CRC family history were associated with adenomas (OR 2.68 CI 1.03-6.98, OR 6.68 CI 1.03-47.98 respectively) and advanced neoplastic lesions (OR 15.03, CI 2.88-78.3; OR 6.46 CI 1.23-33.79, respectively). With respect to celiac disease characteristic, a low adherence to a gluten free diet was independently associated with the presence of adenomas (OR 6.78 CI 1.39-33.20 p=0.01). CONCLUSIONS: Celiac disease was not associated with an increased risk of colorectal neoplasia. Nonadherence to a strict gluten free diet was associated with the presence of adenomas. Further studies addressing celiac disease characteristics are needed to confirm this observation.

[Gastrointestinal bleeding and intestinal perforation due to polyarteritis nodosa in a patient with celiac disease. A case report]. / Hemorragia digestiva y perforación intestinal secundarias a panarteritis nodosa en un paciente con enfermedad celiaca. Presentación de un caso.

Complications of celiac disease could present with intestinal perforation and rarely, gastrointestinal bleeding, which are usually secondary to nongranulomatous ulcerative jejunoileitis or T-cell lymphoma. We describe the case of a 66-year-old male patient with an 8-year history of celiac disease (CD) who presented with recurrent abdominal pain and gastrointestinal bleeding. Several tests were performed to find out possible complications associated to CD. Due to an overt gastrointestinal bleeding, an arteriography was performed and signs of polyarteritis nodosa were found. Vascular disease was aggressive, and despite multiple medical and surgical treatments the patient died. As arteriography is not usually performed for the study of the complications of CD, it is possible that the association between CD and PAN has been underdiagnosed.

[Is the preparation with sodium phosphate purgative for bowel cleansing safe in low-risk patients?]. / Es segura la preparación con laxante de fosfato sódico para la limpieza colónica en pacientes de bajo riesgo?

UNLABELLED: The development of colonoscopy has increased the oral sodium phosphate (OSP) laxative use. OSP complications like hyperphosphatemia with acute and chronic kidney impairment with nephrocalcinosis have been reported. OBJECTIVE: To describe and analyze acute and one year after OSP complications in low risk well hydrated patients. METHODS: We performed a prospective study in 100 consecutive patients undergoing colonic cleansing with OSP for colonoscopy aged 35-74 year, ASA I-II. Exclusion criteria were congestive heart failure, chronic kidney disease, diabetes, liver cirrhosis, intestinal obstruction, decreased bowel motility, increased bowel permeability, hyperparathyroidism. Arterial pressure, hematocrit, serum osmolality, serum phosphate, ionic calcium, electrolytes (Na+, Cl-, K+), creatinine and urea were measured before and after OSP. The day before colonoscopy all the participants entered a 24 hr-period diet consisting in 4 litres of clear fluids and standard OSP dose (30 g at 17:00 and 30 gr at 22:00). Phosphatemia levels post OSP according to patient's weight (> or =, < or = 70 kg) and one year later kidney function were compared. RESULTS: Mean age was 58.9 +/- 8.4 years, 66% of patients were women and mean weight was 71 +/- 13 kg. Kidney function showed no significant difference between pre and post OSP, and after one year values. Hyperphosphatemia appeared in 87%. Hyperphosphatemia was higher in patients with low weight (5.8 mg/dl vs 5.3 mg/dl, P < 0.05). CONCLUSION: OSP complications were reduced through an adequate patient selection in order to avoid risk factors and an effective hydration. Phosphate overload was tolerated without symptoms. Considering high hyperphosphatemia incidence and its relation with weight, to adjust dose related to weight should be evaluated. There was no acute or a year later renal damage.

Effect of the ingestion of a symbiotic yogurt on the bowel habits of women with functional constipation / Efecto de la ingesta de un alimento simbiótico sobre el hábito evacuatorio en mujeres con constipación funcional

Background/aims: functional constipation is a prevalent problem within the western population. There is evidence supporting the fact that the inclusion of pre and probiotics in the diet can favorably modify the intestinal function. The present study evaluates the effect of the consumption of Activia®, a yogurt containing 108 UFC/g of Bifidobacterium animalis (DN-173 010) and fructoligosaccharide, in women between the ages of 18 and 55 with and without functional constipation (Rome II criteria). Methods: after a stabilization and a basal period, women were randomized to receive 2 units/day of Activia or a lacteous dessert without probiotics (control) for a period of 14 days. Afterwards the groups were intercrossed for another 14 days. Results: of the 399 women who started the study, 378 were eligible for study participation. In the group of women with functional constipation (n= 266), the consumption of the symbiotic was associated with a higher bowel evacuation rate (6.1±2.7 depositions/week with Activia vs. 5.0±2.6 dep./week in the control group; P<0.01), an improvement in the quality of the stools according to the Bristol scale (3.6±1.0 vs. 3.4±1.0; P<0.01), a reduced perception of straining effort (1.9±0.8 vs. 2.2±0.9; P<0.01) and a reduced perception of pain associated with defecation (0.1±0.2 vs. 0.2±0.3; P<0.01). In the group of women without constipation (n=112) there were statistically significant variations in equal sense but of smaller magnitude, with the exception of pain which, having a very low vavaluein the basal period, did not experience changes. Conclusion: the consumption of a symbiotic yogurt by women with functional constipation showed a significant improvement in the parameters related with bowel evacuation. The use of this symbiotic food can result in a useful and safe tool for managing constipation.

Introducción/objetivos: la constipación funcional es un problema prevalente en la población occidental. Existen evidencias de que la toma de alimentos pre y probióticos puede modificar favorablemente el hábito evacuatorio intestinal. En este trabajo se estudió el efecto de la ingesta de Activia®, un yogur conteniendo 10 8 UFC/g de Bifidobacterium animalis (DN-173 010) y un fructoligosacárido en mujeres de 18 a 55 años con y sin constipación funcional (criterios de Roma II). Métodos: luego de sendos períodos de estabilización y basal fueron aleatorizadas a recibir durante 14 días 2 unidades/día de Activia o de un postre lácteo sin probiótico ni prebiótico (control). Luego los grupos fueron entrecruzados durante otros 14 días. Resultados: de las 399 mujeres que iniciaron el estudio, 378 fueron evaluables. En el grupo de constipadas (n= 266) la toma del simbiótico se asoció con una mayor frecuencia evacuatoria (6,1±2,7 dep./semana con Activia vs. 5,0±2,6 dep./semana en controles; P<0,01), mejoría en la escala de Bristol de calidad de las heces (3,6±1,0 vs. 3,4±1,0; P<0,01), menor esfuerzo evacuatorio (1,9±0,8 vs. 2,2±0,9; P<0,01) y menor proporción de dolor evacuatorio (0,1±0,2 vs. 0,2±0,3 ; P<0,01). En el grupo sin constipación se observaron variaciones estadísticamente significativas en igual sentido pero de menor magnitud, con excepción del dolor que mostró un valor basal muy bajo. Conclusión: la ingesta del yogurt prebiótico en mujeres con constipación funcional mostró una mejoría significativa de los parámetros relacionados con la evacuación intestinal. La utilización de este alimento simbiótico puede resultar una herramienta útil y segura en el manejo de la constipación.

[Clinical course of inflammatory bowel disease in patients transplanted for primary sclerosing cholangitis]. / Evolución de la enfermedad inflamatoria intestinal en pacientes sometidos a trasplante hepático por colangitis esclerosante primaria.

UNLABELLED: Primary sclerosing cholangitis is frequently associated with inflammatory bowel disease. OBJECTIVE: to evaluate the evolution of IBD in patients transplanted for PSC and the incidence of severe dysplasia/carcinoma. PATIENTS AND METHODS: we included 32 patients transplanted between 1988 and 2006 for PSC. Median follow-up: 8.7 years (1-20 y). All patients were evaluated pre-OLT with colonoscopy and multiple intestinal biopsies. Post-OLT surveillance colonoscopies were performed every 12 months. RESULTS: of 32 patients included, 26 had inflammatory bowel disease pre-OLT (ulcerative colitis 25, Crohn's disease 1). 12 patients had active intestinal disease pre-OLT and 2 patients had moderate dysplasia but were not surgically treated due to the severity of their liver disease. Among the 26 patients with IBD pre-OLT, 2 died in the postoperative period due to complications related to the transplantation procedure. Among the other 24 patients, 16 had a quiescent colonic disease post-OLT. Among them, 12 had quiescent disease pre-OLT and 4 showed improvement in their colonic symptoms after transplantation. Eight patients were symptomatic pre-OLT and had a transitory improvement in their symptoms post-OLT, with worsening of their intestinal disease by 5.7 +/- 2.8 months after transplantation. Three patients developed severe dysplasia or colonic cancer. CONCLUSIONS: over half of patients transplanted for PSC presented with quiescent intestinal disease. Yet, there was a group of patients that worsened their colonic symptoms and had a high incidence of dysplasia/carcinoma. It is necessary to maintain an adequate colonic surveillance even in the absence of colonic symptoms or active disease.

Colitis por drogas antiinflamatorias no esteroides (DAINEs): a propósito de 3 casos / Colitis by nonsteroidal anti-inflammatory drugs (NSAIDs): apropos of 3 cases

Introducción: Los efectos secundarios de los DAINEs sobre el colon no están bien caracterizados con pocas publicaciones reportadas en la literatura. El reconocimiento de estas lesiones es de gran importancia para su correcto manejo. El motivo de esta comunicación es presentar 3 casos de colitis por DAINEs tratados en el Hospital Italiano entre 1994 y 2004. Material y Método: durante el período de 10 años se diagnosticaron 3 casos de ulceras por DIANEs. Estos casos se describen a continuación. Caso 1: hombre de 70 años, clínica: hematoquezia, antecedente de: ingesta crónica de DAINES. Hallazgos endoscópicos: ulceras y estenosis tipo diafragma. Resolución ad-integrum luego de cesación de drogas. Caso 2: mujer de 54 años, que se presenta con cuadro de oclusión colónica. Ante duda diagnóstica se efectúa colectomía derecha. Caso 3: mujer 58 años, clínica: hematoquezia. HalIazgo endoscópico: múltiples ulceras en todo el colon. Tratamiento: mediante suspensión de AINES. Evolución: curación ad-integrum Conclusión: Colitis por AINES es una afección poco frecuente que puede dejar secuelas clínicamente importantes. El diagnóstico de esta afección permite su manejo adecuado. Discontinuar la administración del DAINEs es el primer paso hacia la cura. La dilatación con balones endoscópicos púede ser de utilidad pero la cirugía es mandatoria cuando debe descartarse una neoplasia.

Evaluación de pacientes con enfermedad de Crohn mediante RM con enteroclisis y ecografía Doppler / Doppler ultrasound and MR enteroclysis imaging of Crohn's disease

Objetivo: presentar nuestra experiencia en pacientes con enfermedad de Crohn del intestino delgado evaluados con ecografía Doppler (ED) y resonancia magnética con enteroclisis (RM). Material y métodos: se evaluaron 12 pacientes mediante ED y RM con contraste negativo (bario y metilcelulosa) y gadolinio. Se analizó la presencia de flujo en ED y tinción en la pared de las asas en RM, espesor parietal y complicaciones. Resultados: Todos los pacientes mostraron tinción de la pared por RM y en once flujo por ED. La correlación entre ambos métodos fue total en 10 pacientes. La RM mostró en 10 pacientes áreas de estenosis, mientras que la ecografía en 5 pacientes. Ambos métodos mostraron engrosamiento parietal, y en igual porcentaje fístulas y abscesos. Conclusión: Ambos métodos permiten identificar y cuantificar alteraciones en el intestino delgado en pacientes con enfermedad de Crohn, pudiendo ser útiles en la evaluación y seguimiento de estos pacientes

Colonic proteinase: increased activity in patients in patients with ulcerative colitis

In order to study the colonic intraluminal proteinase-antiproteinase imbalance under inflammatory conditions, we determined proteolytic activity (PA), alpha-1-antitrypsin and the activities of trypsin, chymotrypsin and neutrophil elastase in feces from patients with ulcerative colitis (UC) comparing the results with a control group. A fecal sample was obtained from each of 25 patients with ulcerative colitis and 10 control subjects were studied. The severity of the disease was assessed by the Truelove index. Proteolytic activity was measured lesing azocasein as proteolytic substrate. The fecal concentration of alpha-1-antitrypsin was measured by radial immunodiffusion and the activities of the enzymes were measured using specific substrates. We found an increase in fecal PA, alpha-1-antitrypsin and neutrophil elastase in patients with UC and the correlation between the severity of the disease and the PA was statistically significant (r = 0.62, P < 0.05). We conclude that elevated colonic proteinase activity could contribute to the pathophysiology of ulcerative colitis.