Management of liver and gastrointestinal toxicity induced by immune checkpoint inhibitors: Position statement of the AEEH–AEG–SEPD–SEOM–GETECCU / Manejo de las toxicidades digestivas secundarias al tratamiento con inhibidores de checkpoint: documento de posicionamiento de la AEEH-AEG-SEPD-SEOM-GETECCU

The development of the immune checkpoint inhibitors (ICI) is one of the most remarkable achievements in cancer therapy in recent years. However, their exponential use has led to an increase in immune-related adverse events (irAEs). Gastrointestinal and liver events encompass hepatitis, colitis and upper digestive tract symptoms accounting for the most common irAEs, with incidence rates varying from 2% to 40%, the latter in patients undergoing combined ICIs therapy. Based on the current scientific evidence derived from both randomized clinical trials and real-world studies, this statement document provides recommendations on the diagnosis, treatment and prognosis of the gastrointestinal and hepatic ICI-induced adverse events.(AU)

El descubrimiento de los inhibidores de checkpoint inmunológicos (ICI) es uno de los logros más importantes en los últimos años en Oncología. Sin embargo, su uso en aumento ha conlllevado a un incremento de los efectos adversos inmunomediados (irAEs). Los eventos hepáticos y gastrointestinales incluyen la hepatitis, colitis y síntomas de tracto digestivo superior, que son de los irAEs más frecuentes, con incidencias entre el 2 y 40%, ésta última en paciente tratados con combo de ICI. Basados en la evidencia científica tanto de ensayo clínicos randomizados como de estudio de vida real, este documento de consenso aporta recomendaciones sobre el diagnóstico, tratamiento y pronóstico de los efectos adversos hepáticos y gastrointestinales asociados con la inmunoterapia.(AU)

MSH3-related adenomatous polyposis in a patient with the negative family history of colorectal polyps / Poliposis adenomatosa relacionada con MSH3 en un paciente con antecedentes familiares negativos de pólipos colorrectales

Recently, biallelic MSH3 germline pathogenic/likely pathogenic variants have been recognized as a rare cause of adenomatous polyposis. We present a 49-year-old woman who was admitted to our high-risk colorectal cancer clinic after incidental detection of a biallelic MSH3 (likely) pathogenic variant when tested for the germline (likely) pathogenic variants in hereditary breast and ovarian cancer related genes. The focus of this case report is to describe the genotype and phenotype of our patient with MSH3-related adenomatous polyposis. More than half of the polyps (13/19) were located in the right colon. In addition, benign and malignant extraintestinal lesions may be common as our patient had simple liver and kidney cysts and two basal cell skin carcinomas.(AU)

Recientemente, las variantes patogénicas/probablemente patogénicas de la línea germinal bialélica de MSH3 han sido reconocidas como una causa rara de poliposis adenomatosa. Presentamos a una mujer de 49 años que ingresó en nuestra clínica de cáncer colorrectal de alto riesgo después de la detección incidental de una variante patógena probable de la línea germinal MSH3 bialélica cuando se analizó la línea germinal variantes patogénicas/probablemente patogénicas en genes hereditarios relacionados con el cáncer de mama y de ovario. El objetivo de este informe de caso es describir el genotipo y el fenotipo de nuestro paciente con poliposis adenomatosa relacionada con MSH3. Más de la mitad de los pólipos (13/19) se localizaron en el colon derecho. Además, las lesiones extraintestinales benignas y malignas pueden ser comunes, ya que nuestra paciente tenía quistes hepáticos y renales simples y dos carcinomas cutáneos de células basales.(AU)

Streptococcus bovis infection of the central nervous system in adults: Report of 4 cases and literature review / Infección del sistema nervioso central por Streptococcus bovis en adultos: reporte de 4 casos y revisión de la literatura

Objectives: To describe the clinical features, history and association with intestinal disease in central nervous system (CNS) S. bovis infections. Methods: Four cases of S. bovis CNS infections from our institution are presented. Additionally a systematic literature review of articles published between 1975 and 2021 in PubMed/MEDLINE was conducted. Results: 52 studies with 65 cases were found; five were excluded because of incomplete data. In total 64 cases were analyzed including our four cases: 55 with meningitis and 9 with intracranial focal infections. Both infections were frequently associated with underlying conditions (70.3%) such as immunosuppression (32.8%) or cancer (10.9%). In 23 cases a biotype was identified, with biotype II being the most frequent (69.6%) and S. pasteurianus the most common within this subgroup. Intestinal diseases were found in 60.9% of cases, most commonly neoplasms (41.0%) and Strongyloides infestation (30.8%). Overall mortality was 17.1%, with a higher rate in focal infection (44.4% vs 12.7%; p=0.001). Conclusions: CNS infections due to S. bovis are infrequent and the most common clinical form is meningitis. Compared with focal infections, meningitis had a more acute course, was less associated with endocarditis and had a lower mortality. Immunosuppression and intestinal disease were frequent in both infections.(AU)

Introducción: Streptococcus bovis, una causa bien conocida de endocarditis asociada a cáncer colorrectal, es también una causa poco frecuente de infecciones del sistema nervioso central (SNC), incluyendo meningitis, abscesos cerebrales o empiema subdural. El objetivo de este estudio es describir las características clínicas, los antecedentes médicos y la asociación con la enfermedad intestinal en las infecciones por S. bovis en el SNC. Métodos: Describimos 4 infecciones por S. bovis en el SNC en nuestra Unidad y, a continuación, presentamos una revisión bibliográfica de los artículos publicados entre 1975-2021 en PubMed/MEDLINE. Resultados: Se encontraron 52 estudios con 65 casos; 5 se excluyeron por datos incompletos. En total se analizaron 64 casos incluyendo nuestros 4: 55 con meningitis y 9 con infecciones focales intracraneales. Ambas infecciones se asociaron con frecuencia a condiciones subyacentes (70,3%) como la inmunosupresión (32,8%) o el cáncer (10,9%). En 23 casos se identificó un biotipo, siendo el más frecuente el biotipo ii (69,6%), y dentro de ellos, S. pasteurianus. En el 60,9% de los casos se detectaron enfermedades intestinales, siendo las más frecuentes las neoplasias (41,0%) y la infestación por Strongyloides (30,8%). La mortalidad global fue del 17,1%, con una tasa mayor en la infección focal (44,4 frente a 12,7%; p=0,001). Conclusiones: Las infecciones del SNC debidas a S. bovis son poco frecuentes y la forma clínica más común es la meningitis. En comparación con las infecciones focales, la meningitis tiene un curso más agudo, está menos asociada a la endocarditis y tiene una menor mortalidad. La inmunosupresión y la enfermedad intestinal fueron frecuentes en ambas infecciones.(AU)

Sobrecrecimiento bacteriano intestinal. Documento de posicionamiento ASENEM-SEPD / Small intestinal bacterial overgrowth. A position paper of ASENEM-SEPD

El sobrecrecimiento bacteriano intestinal (SIBO, por sus siglas en inglés) es una entidad descrita desde hace varias décadas, pero que en los últimos años ha cobrado un especial interés por parte de los profesionales médicos y por la población general, probablemente por el aumento de la disponibilidad de pruebas diagnósticas y por la extensa difusión que se le ha dado a esta enfermedad a través de los medios de comunicación y redes sociales. En vista de la gran cantidad de información disponible en la actualidad y en ocasiones discrepante, entre la Sociedad Española de Patología Digestiva (SEPD) y la Asociación Española de Neurogastroenterología y Motilidad (ASENEM) hemos realizado un documento de posicionamiento para establecer líneas de diagnóstico y tratamiento del SIBO con la información científica actualizada.(AU)

ffectiveness and safety of ustekinumab dose escalation in Crohn’s disease: a multicenter observational study / Efectividad y seguridad del aumento de dosis de ustekinumab en la enfermedad de Crohn: un estudio observacional multicéntrico

Background: ustekinumab has proven effective in Crohn’s disease (CD). However, some patients will partially respond or lose response over time. Data supporting the effectiveness of dose escalation in this scenario is scarce. Aim: to evaluate the effectiveness of ustekinumab dose escalation in CD. Methods: patients with active CD (Harvey-Bradshaw ≥ 5) who had received intravenous (IV) induction and at least a subcutaneous (SC) dose were included in this retrospective observational study. Ustekinumab dose was escalated, either via shortening of the interval to six or four weeks or IV reinduction plus shortening to every four weeks. Results: ninety-one patients were included, and ustekinumab dose was escalated after a median of 35 weeks of treatment. At week 16 after intensification, steroid-free clinical response and remission were observed in 62.6 % and 25.3 % of patients, respectively. Systemic corticosteroids were discontinued in 46.7 % of patients who were on corticosteroids at baseline. Follow-up data beyond week 16 were available for 78 % of patients; at the last visit, 66.2 % and 43.7 % were in steroid-free clinical response and remission, respectively. After a median follow-up of 64 weeks, 81 % of patients were still treated with ustekinumab. Adverse events were reported in 4.3 % of patients; these were all mild and did not lead to hospitalization or discontinuation of treatment. Five patients (5.5 %) underwent surgical resection, with no immediate postsurgical complications. Conclusion: ustekinumab dose escalation was effective in recapturing response in over half of the patients. These findings suggest that dose escalation should be considered in patients who experience loss or partial response to the standard maintenance.(AU)

Biomecánica esofágica valorada mediante planimetría por impedancia (EndoFLIP™) en sujetos sanos y en pacientes con esofagitis eosinofílica. Valores de normalidad / Esophageal biomechanics assessed by impedance planimetry (EndoFLIPTM) in healthy subjects and in patients with eosinophilic esophagitis. Normality values

Antecedentes: la esofagitis eosinofílica (EEo) activa se asocia a alteraciones en el calibre, la distensibilidad y la motilidad esofágica que podrían revertir con el tratamiento. Objetivos: estudiar el diámetro, la distensibilidad y la contractilidad esofágica en sujetos sanos comparándolos con pacientes con EEo antes y después del tratamiento. Métodos: estudio cuasiexperimental. Mediante EndoFLIP™, se analizaron el cuerpo esofágico y la unión esofagogástrica (UEG) de los tres grupos, y se diseñó un programa para obtener los valores de diámetro, distensibilidad y contractilidad esofágica. Resultados: incluimos diez voluntarios sanos (24-61 años, seis hombres) y nueve pacientes con EEo (21-52 años, siete hombres). El índice de distensibilidad de la UEG fue de 5,07 mm2/Hg en controles, 2,40 mm2/Hg en EEo antes del tratamiento y 2,46 mm2/Hg después; la meseta de distensibilidad fue de 20,02 mm, 15,43 mm y 17,41 mm, respectivamente; y el diámetro, de 21,90 mm, 17,73 mm y 18,30 mm, con diferencias significativas (p < 0,05) excepto entre los diámetros de controles y pacientes tratados (p = 0,079). Las contracciones anterógradas repetitivas aparecieron en el 90 % de los controles, en el 66,7 % de EEo a antes del tratamiento y en el 88,9 % después (p > 0,05). Conclusiones: el índice de distensibilidad de la UEG, la meseta de distensibilidad y el diámetro en controles son mayores que en pacientes, aunque seis semanas de tratamiento parece poco tiempo para ver cambios significativos en la biomecánica esofágica. Las contracciones anterógradas repetitivas son el patrón predominante en sanos y en EEo. Aportamos valores de normalidad de la biomecánica esofágica medida mediante planimetría por impedancia en nuestro entorno.(AU)

Background: active eosinophilic esophagitis is associated with esophageal caliber, distensibility and motility changes that may be reversed with treatment. Objectives: to study esophageal diameter, distensibility and contractility in healthy subjects compared to patients with eosinophilic esophagitis, both before and after treatment. Methods: a quasi-experimental study, EndoFLIP™, was used to analyze the esophageal body and esophago-gastric junction (EGJ) in all three groups, and a program was designed to obtain esophageal diameter, distensibility and contractility values. Results: ten healthy volunteers (24-61 years, six men) and nine patients with eosinophilic esophagitis (21-52 years, seven men) were included. The esophagogastric junction distensibility index was 5.07 mm2/Hg in the control subjects, 2.40 mm2/Hg in the subjects with eosinophilic esophagitis before treatment and 2.46 mm2/Hg after treatment. The distensibility plateau was 20.02 mm, 15.43 mm and 17.41 mm, respectively, and the diameter was 21.90 mm, 17.73 mm and 18.30 mm, showing significant differences (p < 0.05), except between control subjects and patients after treatment (p = 0.079). Repetitive antegrade contractions developed in 90 % of control subjects, 66.7 % of eosinophilic esophagitis patients before treatment and 88.9 % of the latter after treatment (p > 0.05). Conclusions: esophago-gastric junction distensibility index, distensibility plateau and diameter values were higher in controls than in patients, although six weeks of treatment seems a short period to observe significant changes in esophageal biomechanics. Repetitive antegrade contractions are the predominant pattern in healthy subjects and eosinophilic esophagitis. We provide normality values for esophageal biomechanics, measured by impedance planimetry in our setting.(AU)

FiLaC procedure for highly selected anal fistula patients: indications,safety and efficacy from an observational study at a tertiary referral center / Procedimiento FiLaC para pacientes con fístula anal altamente seleccionados: indicaciones, seguridad y eficacia de un estudio observacional en un centro de referencia terciario

Background: the ideal clinical profile of patients or fistula features for fistula laser closure (FiLaC®) technique remain to be established. The aim of this study was to analyze clinical outcomes and the safety profile of FiLaC® in search for an ideal setting for this technique. Methods: a retrospective observational study was performed from a prospective database including all consecutive patients who underwent surgery for anal fistula (AF) with FiLaC® in the coloproctology unit of a tertiary referral center, between October 2015 and December 2021. The FiLaC® procedure was offered to AF patients who were considered to be at risk of fecal incontinence. Fistulas were described according to Parks’ classification and categorized as complex or simple according to the American Gastroenterological Association (AGA) guidelines. Healing was defined by the closure of the internal and external openings for at least six months. Predictive factors of AF healing were investigated. Results: a total of 36 patients were included, with a mean age of 48 ± 13.9 years. Twenty patients (55.6 %) were male and 13 patients (36 %) had Crohn’s disease (CD). Fourteen patients (38.8 %) had a complex fistula. The primary and secondary healing rates were 55.6 % and 91.7 %, respectively, during a median follow-up time of 12 months (IQR 7-29). No fecal continence impairment was registered in any case. The proportion of patients with primary healing was significantly higher in CD patients (76.9 % vs 43.5 %, p = 0.048). Conclusions: FiLaC® is a sphincter-preserving procedure with an excellent safety profile and reasonable success rate despite of the strict patient selection. This technique may be attractive for patients with CD due to its higher primary healing rate.(AU)

Value of CRP/albumin ratio as a prognostic marker of acute pancreatitis: a retrospective study / Valor del cociente PCR/albúmina como marcador pronóstico de pancreatitis aguda: un estudio retrospectivo

Introduction: the C-reactive protein (CRP) to albumin ratio is an inflammatory marker that has shown promise in the prognosis of critically ill patients. This study is aimed to assess the value of CRP/albumin ratio to predict severity in acute pancreatitis. Methods: a retrospective study was performed using a prospectively collected database of patients diagnosed with AP admitted to the Department of Gastroenterology between March 2014 and December 2021. Results: among 722 patients included in the study, 78.67 % had mild, 15.65 % had moderately severe, and 5.67 % had severe acute pancreatitis. The CRP/albumin ratio was significantly associated with severe AP (OR 1.02; 95 % CI: 1.01-1.03; p < 0.001), and each ten-unit increase in the ratio was associated with a 20 % increased likelihood of severe acute pancreatitis. The area under the ROC curve (AUC) value of the CRP/albumin ratio in severe acute pancreatitis was 0.68 (95 % CI: 0.58-0.77), which was higher than that of the Ranson criteria (0.62). The optimal cut-off value for predicting severe acute pancreatitis was 7.51, with a sensitivity of 63.4 % and specificity of 65.6 %. Conclusions: despite its low sensitivity and specificity, the CRP/albumin ratio could be used as a complementary marker to the current scoring systems for the initial assessment of acute pancreatitis prognosis. It is easily obtainable and can provide additional prognostic information to clinicians.(AU)

Persistencia del conducto onfalomesentérico: otra causa de abdomen agudo / Persistence of the omphalomesenteric duct: another cause of acute abdomen

El conducto onfalomesentérico es una estructura embrionaria que comunica el saco vitelino con el intestino medio, generalmente desapareciendo entre la quinta y la novena semanas de vida intrauterina. La persistencia del conducto onfalomesentérico, presente hasta en un 2% de la población, es una anomalía congénita del tracto gastrointestinal que puede presentarse en forma de abdomen agudo, oclusión intestinal o hemorragia digestiva.(AU)

Iatrogenic Small Intestinal Obstruction / Obstrucción iatrogénica del intestino delgado

An 83-year-old female, suffering from abdominal pain, nausea, and vomiting, was admitted to our hospital. Gas-liquid level and tumor was not seen on the abdominal computed tomography scan. Instead, two high density balloon which were 2.7cm(distal) and 3.3cm(proximal) in diameter separately were shown (Figure A) in small intestine. The balloons proved to be part of ileus tube and iohexol which was incorrectly injected into the balloons caused a blockage in the tube. During colonoscopy, we were surprised to find that the distal balloon had passed through the ileocecal valve and we punctured it easily (Figure B). However, affected by the broken distal balloon, we could not reach another one. Finally, we cut off the connector fixed to the face and instructed the patient to take some oral paraffin oil and exercise appropriately. The next day, the balloons were discharged with the symptoms alleviated. It is rare for iatrogenic foreign body to cause ileal obstruction).(AU)

The role of gastrointestinal endoscopy in Kaposi sarcoma / El papel de la endoscopia gastrointestinal en el sarcoma de Kaposi

We are writing to make endoscopists aware of the paramount of a prompt diagnosis of gastrointestinal Kaposi sarcoma (GI-KS). Patients with GI involvement have a two to five times higher risk of death and will benefit from chemotherapy to improve their survival. However, current evidence found that one out of three patients might have a false negative result even with HHV-8 since other entities such as gastrointestinal stromal tumors, angiosarcoma, and lymphoma shared macroscopic and histopathological characteristics. These cause a delay in treatment and significantly worsen the prognosis. We observed a trend for a positive diagnosis from ulcers and nodules. To our knowledge, this is the largest cohort of patients with GI-KS in the world. Our study suggests that in cases where a complete immunochemistry panel for KS is not available, HHV-8 remains as a bare minimum. However, other gastrointestinal lesions shared histopathological characteristics. Therefore, we suggest taking biopsies from nodular and ulcer-type lesions to increase the probability to establish a histopathological diagnosis.(AU)

Paraneoplastic acquired hemophilia A associated with hilar cholangiocarcinoma arising in an intraductal papillary neoplasm of the bile duct / Paraneoplásico adquirido hemofilia A asociada con colangiocarcinoma hiliar que surge en un papilar intraductal neoplasia del conducto biliar

A 74-year-old female was admitted for painless jaundice. Laboratory tests showed hyperbilirubinemia, cholestasis, normal coagulation, and Ca19-9:163U/L. The CT-scan reported dilation of the intrahepatic and extrahepatic bile ducts secondary to a 24mm tumor in the intrapancreatic common bile duct. The magnetic cholangioresonance showed multiple endoluminal polypoid lesions, suggestive of intraductal papillary neoplasm of the bile duct (IPNB). The endoscopic bile duct brushing was non-conclusive.(AU)

Tratamiento quirúrgico de estenosis duodenal secundaria a enfermedad de Crohn / Duodenal stenosis surgical treatment in Crohn’s disease

We present the case of a 34-year-old man with daily vomiting and 20% weight loss in a year. A gastroduodenoscopy was performed, noticing 2nd and 3rd duodenal portion dilatation and inflammatory involvement of the 3rd and 4th portion, causing luminal stenosis. These findings are the same than in the magnetic resonance . The biopsy proves the histological diagnosis of Crohn's disease. At the beginning the patient was treated with Prednisone, Adalimumab and Ustekinumab. After 9 months, surgery was decided because the disease was refractory to treatment and there was corticosteroid dependence. A partial resection of 3rd and 4th portion of the duodenum and the first loop of jejunum was performed, with duodenojejunal anastomosis. The patient presents good postoperative evolution and after 1 year he remained asymptomatic under treatment with Ustekinumab.(AU)

Primary esophageal follicular lymphoma: a rare entity / Linfoma folicular esofágico primario: una entidad rara

A 63-year-old woman presented with dyspepsia de novo. An esophagogastroduodenoscopy revealed a 30 mm flat yellowish esophageal lesion, 28 cm from the incisors (Fig. 1a), with the stomach and duodenum without any lesion. Helicobacter pylori infection was excluded. Histological examination was suggestive of a lymphoproliferative process (Fig. 1b). Immunohistochemistry showed diffuse positivity for CD20 (Fig. 1c) and BCL-2 (Fig. 1d), dim CD10 and BCL-6 staining, a Ki-67 of 20-25%, no CD21 or cyclin D1 expression, all these features compatible with low-grade follicular lymphoma. Physical examination was unremarkable. Computed tomography of the neck, chest, and abdomen revealed no lymph node enlargement, hepatosplenomegaly or metastasis. Blood routine tests and tumor markers were at normal levels. Bone marrow biopsy showed no involvement by lymphoma. Therefore, a diagnosis of primary follicular lymphoma of the esophagus was made. The patient opted for a watch-and-wait strategy and there is no evidence of disease progression after four years of follow-up.(AU)

Abundancia de Akkermansia muciniphila según el IMC en pacientes con trastornos gastrointestinales: estudio piloto de cohorte transversal / Akkermansia muciniphila abundance according to BMI in patients with GI disorders: cross-sectional cohort pilot study

En los últimos años, Akkermansia muciniphila ha ganado prominencia en la investigación científica debido a su posible contribución a la regulación de la respuesta inmunológica, la sensibilidad a la insulina, la prevención de enfermedades inflamatorias y la salud metabólica. En concreto, su abundancia se ha correlacionado inversamente con el peso corporal y su presencia podría tener un efecto beneficioso en la regulación del metabolismo. El objetivo del presente estudio fue examinar si A. muciniphila estaba asociada con el IMC en personas con trastornos gastrointestinales. Los resultados sugieren que la abundancia de A. muciniphila es muy baja en pacientes con trastornos gastrointestinales (1,35%) y menor en personas con sobrepeso u obesidad, aunque los resultados no fueron significativos. Este estudio no pudo confirmar de forma estadísticamente significativa la hipótesis de la relación entre Akkermansia y el sobrepeso o la obesidad. Lo cual puede sugerir o una potencia del efecto menor del mismo al esperado, o la no relación directa o causal.(AU)

In recent years, Akkermansia muciniphila has gained prominence in scientific research due to its potential contribution to the regulation of immune response, insulin sensitivity, prevention of inflammatory diseases, and metabolic health. Specifically, its abundance has been inversely correlated with body weight, and its presence may have a beneficial effect on metabolism regulation. The aim of this study was to examine whether A. muciniphila was associated with BMI in individuals with gastrointestinal disorders. The results suggest that the abundance of A. muciniphila is very low in patients with gastrointestinal disorders (1.35%) and lower in individuals with overweight or obesity, although the results were not significant. This study could not confirm in a statistically significant way the hypothesis of the relationship between Akkermansia and overweight or obesity. Which may suggest either a lower power of the effect than expected, or no direct or causal relationship.(AU)