Revista Española de Enfermedades Digestivas

Point of care testing for paediatric coeliac disease in the new ESPGHAN era

Efficacy of a point-of-care test based on deamidated gliadin peptides for the detection of celiac disease in pediatric patients

Objective: The objective of the study was to assess the effectiveness of a point-of-care test (POCT) based on deamidated gliadin peptides (DGP) compared to the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) criteria diagnosis in the early detection of celiac disease (CD) in pediatric patients. Methods: One hundred children (≤ 18 years) with suspected CD were selected, including siblings of celiac children that underwent gastroscopy for other gastrointestinal conditions. Patients with severe disease, following a gluten-free diet (GFD), with gastrointestinal bleeding, coagulopathy and infections in the last month were excluded. All children were evaluated with a POCT that detects immunoglobulin A (IgA) and immunoglobulin G (IgG) antibodies to DGP and total IgA. The POCT results were compared to CD diagnosis according to current ESPGHAN criteria. This involved the detection of IgA tissue transglutaminase (tTG) antibodies, the results of an intestinal biopsy and genetic testing. Results: The prevalence of CD found in the present study was 48% (95% confidence interval in parenthesis 37.9-58.2%). The results of the POCT were concordant with the CD diagnosis made according to ESPGHAN criteria: 95.8% (85.7-99.4%) sensitivity, 98.1% (89.7-99.7%) specificity, 97.9% (88.7-99.6%) positive predictive value and 96.2% (87.0-99.4%) negative predictive value. Positive and negative likelihood ratios were 49.8 (7.2-347.5) and 0.04 (0.01-0.17), respectively. The POCT showed a 100% diagnostic accuracy in children younger than ten years of age. In total, three discordant results were found. Conclusion: Due to the high diagnostic accuracy in the pediatric population, the POCT can be considered as an effective tool for the early diagnosis of CD, especially in patients younger than ten years of age.

**Recurrencia de infección y diversidad de cepas de Helicobacter pylori en adultos tratados con terapia triple estándar empírica en una población de México**

Background: After eradication treatment for Helicobacter pylori (H. pylori), infection could recur due to recrudescence or re-infection. The objective of this study was to determine the recurrence of H. pylori infection and identify virulent H. pylori strains one year after eradication with standard triple therapy. Material and methods: A quasi-experimental study was performed that included a patient population with digestive diseases associated with H. pylori who had received standard triple therapy. Cultures and polymerase chain reaction (PCR) was performed on gastric biopsies for strain identification in all patients prior to eradication treatment and those with a positive carbon-14 breath test one year after eradication treatment. Statistical analysis was performed using the Student's t-test and Fisher's exact test; statistical significance was set at 0.05. Results: One hundred and twenty-eight patients were studied, 51 (39.8%) were male and 77 (60.2%) were female with an average age of 54.8 years (DE 13.8). There was an annual recurrence of H. pylori infection in 12 (9.3%) patients. An annual re-infection and recrudescence occurred in nine (7%) and three (2.3%) patients respectively. The recrudescence rate for antigenic protein (cagA) was 1/30 (3.3%) patients and 2/112 (1.8%) patients for vacuolating cytotoxin (vacA). The re-infection rate for cagA was 3/30 (10%) patients and 6/112 (5.3%) patients for vacA. Conclusions: The recurrence of infection in this study was higher than that recorded in developed countries with a low prevalence of H. pylori and lower than that recorded in developing countries with a higher prevalence of H. pylori. The cagA or vacA s2/m2 strains were isolated after re-infection and recrudescence.

Introducción: posterior al tratamiento erradicador de Helicobacter pylori (H. pylori), podría presentarse recurrencia de infección debido a recrudescencia o reinfección. El objetivo de este estudio fue determinar la recurrencia de infección por H. pylori e identificar cepas virulentas de H. pylori al año posterior de su erradicación con terapia triple estándar. Material y métodos: se realizó un estudio cuasiexperimental. La población estudiada fueron pacientes con enfermedades digestivas asociadas a H. pylori que recibieron terapia triple estándar. Todos los pacientes antes del tratamiento erradicador, y solo aquellos pacientes con prueba de aliento con carbono 14 positivo un año posterior al tratamiento se les realizaron cultivos y reacción en cadena de la polimerasa (PCR) de biopsias gástricas para identificación de cepas. Se realizó análisis estadístico mediante el test t de Student y prueba exacta de Fisher, con un nivel de significancia de 0,05. Resultados: se revisaron 128 pacientes, 51 (39,8%) hombres y 77 (60,2%) mujeres, con una edad promedio de 54,8 (DE 13,8) años. Se halló recurrencia anual de infección por H. pylori en 12 (9,3%) pacientes y reinfección y recrudescencia anual en nueve (7%) y tres (2,3%) pacientes respectivamente. La tasa de recrudescencia en proteína antigénica (cagA) fue de 1/30 (3,3%) pacientes y en citotoxina vacuolizante (vacA) fue de 2/112 (1,8%) pacientes. La tasa de reinfección en cagA fue 3/30 (10%) pacientes y en vacA 6/112 (5,3%) pacientes. Conclusiones: en este estudio la recurrencia de infección fue mayor que en países desarrollados con baja prevalencia de H. pylori y menor que en países en vías de desarrollo con mayor prevalencia de H. pylori. Las cepas cagA o vacA s2/m2 fueron aisladas en reinfección y recrudescencia.

Evolution of the incidence of inflammatory bowel disease in Southern Spain

Background: The incidence of inflammatory bowel disease is increasing in Europe and in Spain. However, there is no recent data from Southern Spain. Objectives: To determine the evolution of the hospital incidence of inflammatory bowel disease in Southern Spain. Material and methods: A retrospective study was performed in two hospitals in Southern Spain. Data was collected from inflammatory bowel disease patients, divided into two periods (1995-2000 and 2001-2014) and compared. The reference population from both areas was 1,011,555 inhabitants. Results: A total of 430 patients were registered during the first period (1995-2000); 50% (215) had Crohn's disease that resulted in a cumulative incidence rate of 7.08 cases/100,000 inhabitants per year. The overall inflammatory bowel disease incidence was 3.54 cases/100,000 inhabitants per year. During the second period (2001-2014), 2,089 patients were collected; 51.7% had ulcerative colitis (1,081). The rate of cumulative incidence of inflammatory bowel disease was 14.7 cases/100,000 inhabitants per year (7.6 cases of ulcerative colitis/100,000 inhabitants/year and 7.1 cases of Crohn's disease/100,000 inhabitants/year). Conclusions: The incidence of inflammatory bowel disease in Southern Spain has doubled in the last decade and is similar to that of the rest of the country and Europe.

**Ultrasonografía endoscópica versus tomografía computarizada en la estadificación preoperatoria del cáncer gástrico**

Introduction: Endoscopic ultrasonography (EUS) is the gold standard technique in loco-regional staging of gastric adenocarcinoma (GAC). Nevertheless, the introduction of multidetector-row computed tomography (MDCT) allows accurate studies to be performed. Objective: To compare the diagnostic yield of EUS and MDCT in loco-regional preoperative staging of gastric adenocarcinoma. Material and methods: This was a retrospective and comparative study of all surgical patients with GAC and preoperative staging by EUS and 64-row MDCT. The results for each case were compared with the histological data. Results: Seventy seven surgical patients with GAC were identified and forty two had a complete preoperative staging and were finally included in the study. With regard to overall accuracy of T staging, EUS was superior to MDCT (62% vs 50%). In a subanalysis of early stages (T1-T2) and advanced stages (T3-T4), accuracy and sensitivity (S) were higher for EUS than for MDTC (83.3% vs 64.29% and 84.4% vs 59.5% respectively), although this did not reach statistical significance. The overall accuracy and sensitivity of EUS for N staging was lower than that for MDCT, although neither comparison reached statistical significance (57% vs 64% and 29% vs 55%). Conclusions: EUS diagnostic yield is similar to new MDCT with regard to T and N preoperative staging of GAC. Nevertheless, both techniques should be considered as complementary until more extensive and randomized studies can confirm these results.

Introducción: la ultrasonografía endoscópica (USE) es la técnica de elección para la estadificación loco-regional del adenocarcinoma gástrico (ACG). Sin embargo, la introducción de la tomografía computarizada multidetector (TCMD) permite obtener estudios de muy alta calidad diagnóstica. Objetivo: nuestro objetivo fue comparar la rentabilidad diagnóstica de la USE frente a la TCMD en la estadificación loco-regional preoperatoria de los pacientes con ACG. Material y métodos: se realizó un estudio retrospectivo y comparativo entre pacientes intervenidos de ACG con estadificación preoperatoria mediante USE y TCMD de 64 filas, comparando en cada caso los resultados con el informe anatomopatológico final. Resultados: se analizaron 77 pacientes intervenidos de ACG, incluyéndose finalmente 42 que disponían de estadificación completa. Para la estadificación "T", la precisión diagnóstica (PD) global de USE fue superior a la de TCMD (62% vs. 50%). En un subanálisis entre estadios precoces (T1-2) y avanzados (T3-T4), la PD y sensibilidad (S) de la USE resultaron ser superiores a las de la TCMD (83,3% vs. 64,29% y 84,4% vs. 59,5% respectivamente), aunque sin alcanzarse niveles de significación estadística. Respecto al estadio N, la PD y S de la USE resultaron inferiores a las de la TCMD, aunque tampoco se alcanzaron diferencias estadísticamente significativas (57% vs. 64% y 29% vs. 55%). Conclusiones: en nuestra experiencia, la rentabilidad diagnóstica de la ecoendoscopia es similar a la de los nuevos TCMD en la estadificación preoperatoria T y N en pacientes con ACG. Sin embargo, ambas técnicas deberían considerarse complementarias hasta que estudios más extensos y aleatorizados puedan confirmar estos resultados.

Colonic diverticulosis and the metabolic syndrome: an association?

Background and objectives: Colonic diverticulosis (CD) is related to advanced age and a lack of dietary fiber. Recently, several studies have shown that metabolic syndrome (MS) is also implicated in the etiopathogenesis of CD. This study aimed to assess the association between MS, obesity and CD. Methods: This was a prospective study of a one-year duration. The MS was defined according to the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III). Demographic data, risk factors for MS and endoscopic findings of patients who underwent a total colonoscopy in the department were collected. Obesity was defined as a body mass index ≥ 30 kg/m². Informed consent was obtained. The local Ethics Committee and National Data Protection Committee approved the study. Statistical analysis was performed with SPSS 21 and statistical significance was defined as p < 0.05. Results: The study included 203 patients, 95 males with a mean age of 65.5 years. CD was diagnosed in 30.5% of patients. Univariate analysis showed that age, hypertension, increased waist circumference and hyperlipidemia were associated with colonic diverticulosis. There was no association with gender, obesity or type 2 diabetes mellitus. Multivariate analysis showed that age and a greater waist circumference increased the risk of diverticulosis. Age-adjusted analysis showed that MS was associated with diverticulosis. The prevalence of adenoma in patients with CD was similar to that in patients without CD. Conclusion: In this series, MS was significantly associated with CD. The identification of risk groups is important since diverticulosis can have serious and potentially fatal complications. To our knowledge, this is the first Southern European prospective study evaluating the association between MS and CD.

Insulin resistance and the metabolic syndrome are related to the severity of steatosis in the pediatric population with obesity

Background: To determine the factors associated with an increased risk for severe steatosis (SS) and establish the Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) as a screening tool. Methods: A cross-sectional study was performed in obese children to assess the relationship between the metabolic syndrome (MetS) and glucose metabolism alterations (GMA) and the risk for severe steatosis. Results: A total of 94 children (51 males) aged from six to 14 years were included. Thirteen children (14.8%) had severe steatosis (SS). The anthropometric variables associated with SS included body mass index (BMI) (SS 34.1 vs non-SS 29.7, p = 0.005), waist circumference (cm) (100 vs 92.5, p = 0.015) and hip circumference (cm) (108 vs 100, p = 0.018). The blood parameters included alanine aminotransferase (ALT) (UI/dl) (27 vs 21, p = 0.002), gamma-glutamil transpeptidase (GGT) (UI/dl) (16 vs 15, p = 0.017), fasting glycemia (mg/dl) (96 vs 88, p = 0.006), fasting insulin (UI/dl) (25 vs 15.3, p < 0.001) and HOMA-IR score (7.1 vs 3.7, p < 0.001). Eighteen children with MetS were found to be at an increased risk for severe steatosis (odds ratio [OR] 11.36, p < 0.001). After receiver operating characteristic (ROC) curve analysis, the best area under the curve (AUC) was obtained for HOMA-R of 0.862. The HOMA-R 4.9 cut-off value had a 100% sensitivity (CI 95%: 96.2-100) and 67.9% specificity (CI 95%: 57.1-78.7) for severe steatosis. Conclusions: The presence of MetS and glucose metabolism alterations are risk factors for severe steatosis. The 4.9 cut-off value for HOMA-IR may be a risk factor for severe steatosis in obese children.

Tumores quísticos neuroendocrinos de páncreas (cPNET): revisión sistemática y metaanálisis de series de casos

Cystic pancreatic neuroendocrine tumors represent 13% of all neuroendocrine tumors. The aim of this study is to analyze the phenotype and biologic behavior of resected cystic neuroendocrine tumors. A systematic review and meta-analysis were conducted until September 2016 using a search in Medline, Scopus, and EMBASE with the terms "cystic pancreatic endocrine neoplasm", "cystic islets tumors" and "cystic islets neoplasms". From the 795 citations recovered 80 studies reporting on 431 patients were selected. 87.1% (n = 387) were sporadic tumors and 10.3% (n = 40) corresponded to multiple endocrine neoplasia type 1. Were diagnosed incidentally 44.6% (n = 135). Cytology was found to have a sensitivity of 78.5%. Were non-functional tumors 85% (n = 338), and among the functional tumors, insulinoma was the most frequent. According to the European Neuroendocrine Tumor Society staging, 87.8% were limited to the pancreas (I-IIb), and 12.2% were advanced (III-IV). Disease-free survival at 5 years in stages (I-IIIa) and (IIIb-IV) was 91.5% and 54.2%, respectively; and was significantly lower (p = 0.0001) in functional tumors. In patients with multiple endocrine neoplasia there was a higher incidence of functional (62.5%) and multifocal (28.1%) tumors. Disease-free survival at 5 and 10 years was 60%. Cystic pancreatic neuroendocrine tumors exhibit phenotypical characteristics which are different to those of solid neuroendocrine tumors.

Los tumores quísticos neuroendocrinos representan entre el 13% de los tumores neuroendocrinos de páncreas. El objetivo del trabajo es realizar una revisión sistemática y un metaanálisis de las series de casos descritas. Se realizó una revisión sistemática hasta septiembre de 2016 mediante una búsqueda en Medline, Scopus y EMBASE con los términos: "cystic pancreatic endocrine neoplasm", "cystic islets tumors" y "cystic islets neoplasms". De 795 citas se seleccionaron 80 estudios que describían 431 pacientes, incluyendo 5 casos propios. El 87,1% (n = 387) eran tumores esporádicos y el 10,3% (n = 40) correspondían a neoplasia endocrina múltiple tipo 1. El 44,6% (n = 135) fueron diagnosticados de forma incidental. La citología mostró una sensibilidad del 78,5%. El 85% (n = 338) eran tumores no funcionantes; y el insulinoma fue el más frecuente entre los funcionantes. Según la estadificación European Neuroendocrine Tumor Society, el 87,8% estaban limitados al páncreas (I-IIb) y el 12,2% eran avanzados (III-IV). La supervivencia libre de enfermedad a los 5 años en estadios (I-IIIa) y en los estadios (IIIb-IV) fue del 91,5% y 54,2% respectivamente; y fue significativamente menor (p = 0,0001) en los tumores funcionantes. En los pacientes con MEN-1 hubo mayor incidencia de funcionantes (62,5%) y multicéntricos (28,1%). Los tumores quísticos neuroendocrinos de páncreas expresan un fenotipo diferente a los tumores endocrinos sólidos, pero tienen un pronóstico similar, tras la resección a excepción de los tumores hereditarios.

Eluxadoline en el tratamiento del síndrome de intestino irritable con predominio de diarrea: Punto de vista SEPD

Functional gut disorders, including diarrhea-predominant irritable bowel syndrome, are highly prevalent conditions worldwide that significantly impact health economy and patient quality of life, yet lacking fully satisfactory therapeutic options. These circumstances fostered research on various molecules with more specific therapeutic targets, including opioid receptors. Eluxadoline (Allergan's Vibercy® in the USA, Truberzi® in Europe) is a locally-acting mixed µ- and κ-opioid receptor agonist, and δ-opioid receptor antagonist, that was licensed in 2015 by the Food and Drug Administration (FDA) and in 2016 by the European Medicines Agency (EMA) for use in diarrhea-predominant irritable bowel syndrome. Eluxadoline provides, with advantage over the current standard of care, control of both stool consistency and abdominal pain, good tolerability in most cases, and improved quality of life, hence it deserves consideration when approaching a patient with this disorder. As with any recently approved therapy, adequate pharmacovigilance is to be expected, as well as studies to inform on different scenarios such as on-demand therapy, loss of response assessment, use as rescue therapy for other molecules, and cost-effectiveness, to further characterize and more accurately position eluxadoline within the therapeutic spectrum.

Los trastornos funcionales del tubo digestivo, entre los que se encuentra el síndrome de intestino irritable con predominio de diarrea, constituyen una patología muy prevalente en todo el mundo, con un gran impacto tanto económico como en la calidad de vida de los pacientes, que no cuenta con alternativas terapéuticas completamente satisfactorias. Estas circunstancias han propiciado la investigación de diferentes moléculas con unas dianas terapéuticas más específicas como los receptores opioides. Eluxadoline (Vibercy® en Estados Unidos/Truberzi® en Europa, de Allergan) es una molécula agonista con efectos locales mixtos tanto agonista de los receptores opioides µ- y κ- como antagonista del receptor δ-opioide, que fue aprobada en 2015 por la Food and Drug Administration (FDA) y en 2016 por la Agencia Europea del Medicamento (EMA) para su indicación en el síndrome de intestino irritable con predominio de diarrea. Eluxadoline es un fármaco que ofrece, con ventaja sobre los que se utilizan en esta patología, el control tanto de la consistencia de las deposiciones como del dolor abdominal, con una buena tolerancia en la mayoría de los casos y una mejoría en la calidad de vida de estos pacientes, por lo que es una molécula a considerar en el abordaje de esta patología. Como en todo producto de reciente incorporación terapéutica, es de esperar una farmacovigilancia adecuada así como que se vaya generando conocimiento de estudios que nos ofrezcan información sobre diferentes escenarios tales como el tratamiento a demanda, la valoración de la pérdida de respuesta, la utilización del tratamiento como rescate a otras moléculas y la valoración del coste-eficacia del fármaco, para caracterizar y posicionar de una manera más precisa eluxadoline dentro del espectro terapéutico.

Shunt intrahepático portocava en paciente con quiste hidatídico que comprime vena cava inferior

Serrated polyposis syndrome associated with long-standing inflammatory bowel disease

Inflammatory bowel disease (IBD) patients are at an increased risk of developing colorectal cancer (CRC), which is thought to develop via the adenoma-carcinoma pathway. Since the discovery of the serrated carcinogenesis pathway and serrated polyposis syndrome (SPS), the incidence of carcinomas arising from serrated lesions in IBD patients has increased. We report three cases of long-standing IBD patients with associated serrated polyposis syndrome. At present, the pathophysiology of serrated lesions in IBD patients is not fully understood and there is a lack of strong evidence to confirm whether the manifestation of both conditions represents an increased risk of developing cancer. Therefore, more accurate surveillance guidelines are needed and are being actively investigated at present.

**Tratamiento de pancreatitis recidivante por páncreas divisum y ansa pancreática mediante técnica de Rendez-Vous guiada por ecoendoscopia**

Endoscopic treatment of pancreatic ductal malformations causing recurrent acute pancreatitis, such as pancreas divisum or ansa pancreatica, is mainly based on the sphincterotomy of the minor papilla. However, the technical complexity of conventional endoscopic retrograde cholangiopancreatography (ERCP) is increased in patients presenting anatomical variants like these and it may be unsuccessful. We report the case of a pancreas divisum combined with ansa pancreatica and describe the cannulation and sphincterotomy of the minor papilla using an ultrasound-assisted Rendez-Vous technique.

El tratamiento endoscópico de malformaciones ductales pancreáticas causantes de pancreatitis aguda de repetición, como el páncreas divisum o el ansa pancreática, se basa fundamentalmente en la esfinterotomía de la papila minor. En estos casos, no obstante, la complejidad técnica de la colangiopancreatografía endoscópica retrógrada (CPRE) convencional es mayor, pudiendo resultar fallida. Presentamos el caso de un páncreas divisum completo combinado con ansa pancreática, sintomático, en el que, tras fracasar el acceso endoscópico convencional a la papila minor, se logra la canulación y esfinterotomía de esta mediante técnica de Rendez-Vous guiada ecoendoscópicamente.

Hepatitis de etiología múltiple en hombres VIH positivos que tienen sexo con otros hombres

Hiperbilirrubinemia conjugada tras cirugía: sospecha de síndrome de Dubin-Johnson y confirmación mediante estudio genético

Short-term outcome of patients with colon cancer diagnosed by symptoms and screening

Hematoma subcapsular hepático post-colangiopancreatografía retrógrada endoscópica

Enfermedad venooclusiva hepática inducida por hierbas medicinales chinas

De la utopía a la realidad: incremento de supervivencia en la carcinomatosis peritoneal tratada mediante citorreducción y quimioterapia intraperitoneal hipertérmica