Revista Española de Enfermedades Digestivas

Microbiota gástrica y carcinogénesis: evidencia actual y controversias

**Gastric microbiota and carcinogenesis: the role of non-Helicobacter pylori bacteria: a systematic review**

Background and aim: Helicobacter pylori is the strongest risk factor for gastric cancer. However, recent advances in DNA sequencing technology have revealed a complex microbial community in the stomach that could also contribute to the development of gastric cancer. The aim of this study was to present recent scientific evidence regarding the role of non-Helicobacter pylori bacteria in gastric carcinogenesis. Methods: A systematic review of original articles published in PubMed in the last ten years related to gastric microbiota and gastric cancer in humans was performed. Results: Thirteen original articles were included. The constitution of gastric microbiota appears to be significantly affected by gastric cancer and premalignant lesions. In fact, differences in gastric microbiota have been documented, depending on Helicobacter pylori status and gastric conditions, such as non-atrophic gastritis, intestinal metaplasia and cancer. Gastric carcinogenesis can be associated with an increase in many bacteria (such as Lactobacillus coleohominis, Klebsiella pneumoniae or Acinetobacter baumannii) as well as decrease in others (such as Porphyromonas spp, Neisseria spp, Prevotella pallens or Streptococcus sinensis). However, there is no conclusive data that confirms if these changes in microbiota are a cause or consequence of the process of carcinogenesis. Conclusions: Even though there is limited evidence in humans, microbiota differences between normal individuals, pre-malignant lesions and gastric cancer could suggest a progressive shift in the constitution of gastric microbiota in carcinogenesis, possibly resulting from a complex cross-talk between gastric microbiota and Helicobacter pylori. However, further studies are needed to elucidate the specific role (if any) of different microorganisms.

Risk factors for tuberculosis in inflammatory bowel disease: anti-tumor necrosis factor and hospitalization

Aims: To determine risk factors for active tuberculosis in patients with inflammatory bowel diseases. Methods: Retrospective, case-control study at 4 referral hospitals in Spain. Cases developed tuberculosis after a diagnosis of inflammatory bowel disease. Controls were inflammatory bowel disease patients who did not develop tuberculosis. For each case, we randomly selected 3 controls matched for sex, age (within 5 years) and time of inflammatory bowel disease diagnosis (within 3 years). Inflammatory bowel disease characteristics, candidate risk factors for tuberculosis and information about the tuberculosis episode were recorded. Multivariate analysis and a Chi-squared automatic interaction detector were used. Results: Thirty-four cases and 102 controls were included. Nine of the 34 cases developed active tuberculosis between 1989 and 1999, and 25 became ill between 2000 and 2012. Multivariate regression showed an association between active tuberculosis and anti-TNF (tumor necrosis factor) therapy in the previous 12 months (OR 7.45; 95% CI, 2.39-23.12; p = 0.001); hospitalization in the previous 6 months (OR 4.38; 95% CI, 1.18-16.20; p = 0.027); and albumin levels (OR 0.88; 95% CI, 0.81-0.95; p = 0.001). The median time between the start of biologic therapy and the onset of active tuberculosis was 13 (interquartile range, 1-58) months. Tuberculosis developed after a year of anti-TNF therapy in 53%, and late reactivation occurred in at least 3 of 8 patients. Conclusions: The main risks factors for developing tuberculosis were anti-TNF therapy and hospitalization. Over half the cases related to anti-TNF treatment occurred after a year.

Previous exposure to biologics and C-reactive protein are associated with the response to tacrolimus in inflammatory bowel disease

Background and aims: Inflammatory bowel disease is a chronic disorder of the gastrointestinal tract. Tacrolimus is a calcineurin inhibitor used in the prophylaxis of rejection after a solid organ transplant. There is some evidence for its use in inflammatory bowel disease, although there is a lack of information about the patients who will benefit the most with this drug and the prognostic factors for a favorable response. Material and Methods: We performed a multicentric retrospective study evaluating all the patients who have received tacrolimus in the last 10 years as a treatment for IBD in our area. Results: A total of 20 patients, 12 with Crohn's disease and 8 with ulcerative colitis, were included in four hospitals. The two most common indications were steroid-dependency and fistulizing Crohn's disease. The median time receiving tacrolimus was 11 months. In 12 patients the treatment was stopped. The main reasons for drug withdrawal were absence or loss of response. The median clinical follow-up was 35.5 months. Overall, a 25% achieved clinical remission and 40% were in partial response. Biologic-naïve patients demonstrated a significantly better remission rate as compared with those that were not (80 vs. 7%). Patients who achieved remission were more likely to have a significant reduction in C-reactive protein values 1 month after starting the drug. Seven patients required surgery during the follow- up period. Conclusions: Patients naïve to biologics showed a significantly better response to tacrolimus. A reduction in C-reactive protein one month after starting this drug was associated with clinical remission.

Early precut is as efficient as pancreatic stent in preventing post-ERCP pancreatitis in high-risk subjects: a randomized study

Background: The most common adverse event of endoscopic retrograde cholangiopancreatography is pancreatitis. Precut sphincterotomy has been regarded as a risk factor. Some authors have stated that early precut may actually reduce post-ERCP pancreatitis risk. However, early precut as a preventive measure has not been compared to other preventive measures, such as pancreatic duct stent placement. Aim: To compare the efficacy of early precut sphincterotomy versus pancreatic duct stent placement in high-risk subjects undergoing endoscopic retrograde cholangiopancreatography for the prevention of post-endoscopic cholangiopancreatography. Materials and Methods: This was a single-blinded, randomized trial that took place in two tertiary referral centers in Buenos Aires, from November 2011 to December 2013. ERCP subjects presented at least one of the following risk factors: female sex, age less than 40 years, clinical suspicion of sphincter of Oddi dysfunction, previous pancreatitis, and/or common bile duct diameter of less than 8 mm. Only those who presented a difficult biliary cannulation were randomized into two groups: those who received early precut sphincterotomy and those in whom persistency of biliary cannulation was intended, with subsequent pancreatic duct stent placement after cholangiography was achieved. The incidence of post-ERCP pancreatitis, as well as other adverse events incidence, was compared. Results: Overall, 101 patients were enrolled, 51 in the pancreatic duct stent group and 50 in the early precut group. Pancreatitis rate was similar in both groups (3.92% vs. 4%, p NS). In all cases, pancreatitis was classified as mild. There were no deaths registered. Conclusion: Early precut was associated with an incidence of adverse events similar to pancreatic duct stent placement.

Association between the location of colon polyps at baseline and surveillance colonoscopy: a retrospective study

Introduction: Several factors are used to stratify the probability of polyp recurrence. However, there are no studies correlating the location of the initial polyps and the recurrent ones. The aim of this study was to verify whether the polyp location at the surveillance colonoscopy was correlated with the location of the previously excised polyps at the baseline colonoscopy. Methods: A retrospective study of patients submitted to colonoscopy with presence and excision of all polyps, followed by a surveillance colonoscopy. Polyp location was divided into proximal/distal to splenic flexure and rectum. Characteristics and recurrent rates at the same colon location were also evaluated. Results: Out of the 346 patients who underwent repeated colonoscopy, 268 (77.4%) had at least 1 polyp detected. For all the segments there was an increased risk of recurrent polyps in the same location and it was about four times higher in proximal (OR 3.5; CI 2.1-6.0) and distal colon segments (OR 3.8; CI 2.1-6.8), followed by three times higher in the rectum (OR 2.6; CI 1.5-4.6). No difference was found between the rates of recurrence at the same segment, taking into consideration the polyp morphology, size, polypectomy technique employed and histological classification. Conclusion: There seems to be a significant association between polyp location at baseline and surveillance colonoscopy.

Tratamiento endoscópico de las estenosis malignas de la vía biliar: puesta al día y puntos más relevantes para la práctica clínica habitual

The present review describes the various indications of biliary stent placement in patients with biliary malignancies. It deals in depth with biliary accesses and their effectiveness, as well as with the use of different stents according to lesion type and expected patient survival. For liver hilum lesions, which are somewhat more complex, the usefulness of and need for unilateral or bilateral drainage is assessed, as it is the most appropriate method. All in all, this is an up-to-date literature review that may help clinicians in their daily decision-making, as well as to improve and optimize patient outcomes.

En la presente revisión se describen las diferentes indicaciones para la colocación de prótesis biliares en pacientes con neoplasias malignas de la vía biliar. Se profundiza en los accesos a la vía biliar y en la efectividad de los mismos, así como en el uso de las diferentes prótesis en función del tipo de lesión y de la expectativa de sobrevida del paciente. En las lesiones de hilio hepático, algo más complejas, se valoran la utilidad y necesidad de un drenaje uni- o bilateral y el método más apropiado. En conjunto, se trata de una revisión actual de la literatura que puede ayudar al clínico a la toma de decisiones en su práctica diaria y a mejorar y optimizar los resultados en los pacientes.

Upper gastrointestinal bleeding in a patient with Sjögren syndrome

The missing piece

Over-the-scope clip closure of gastrocutaneous fistula

Granuloma por hilo de sutura no reabsorbible como simulador de implante metastásico retroperitoneal en paciente con neoplasia de sigma

Úlcera rectal postradioterapia complicada con infección por Actinomyces

Tríada de Rigler en íleo biliar

Pseudoaneurisma asociado a pseudoquiste pancreático complicado

A pseudoaneurysm associated with a pseudocyst is a serious and unusual complication of chronic pancreatitis. Its treatment is complex due to its elevated mortality and the need for multidisciplinary management. Initial measures consist of locating the hemorrhage through computerized dynamic tomography and arteriography. The treatment of choice is controversial due to the lack of controlled studies. For managing hemorrhages in stable patients, the most accepted initial measure is currently arterial embolization. In the event of failure of the same, hemodynamic instability or the impossibility of drainage of the pseudocyst, surgery is the subsequent therapeutic option.

El pseudoaneurisma asociado a pseudoquiste es una complicación grave e infrecuente de la pancreatitis crónica. Su tratamiento es complejo por su elevada mortalidad y la necesidad de un manejo multidisciplinar. La medida inicial consiste en la localización de la hemorragia mediante tomografía computarizada dinámica y arteriografía. El tratamiento de elección es controvertido por la ausencia de estudios controlados. Para el manejo de la hemorragia en pacientes estables, la medida terapéutica inicial más aceptada actualmente es la embolización arterial. Ante fracaso de la misma, inestabilidad hemodinámica o imposibilidad de drenaje del pseudoquiste la cirugía es la siguiente opción terapéutica.

Rare association of celiac disease with myasthenia gravis in a patient with other immune disorders: a Case Report

Background: Celiac disease is described in association with several autoimmune diseases, but rarely with myasthenia gravis. Case Report: We describe the case of a 31-year-old white woman with celiac disease who presented manifestations related to a hyperactive immune system, including macroamylasemia, false-positive anti-HCV, positive antinuclear antibody, and Raynaud's phenomenon. The Introduction of a gluten-free diet (GFD) resolved these features, but myasthenia gravis (MG) symptoms unexpectedly occurred on that occasion. Discussion: The role of a GFD in the course of autoimmune diseases has been studied and improvement has been reported in many diseases. However, there is no consensus in the literature regarding the course of neurological disorders associated with celiac disease. In the present case, a GFD did not prevent the appearance of symptoms related to myasthenia gravis. There are few reports on the association of celiac disease with myasthenia gravis and therefore little is known about the course and time of onset of myasthenia in celiac patients. The present case increases the knowledge about this unusual autoimmune neurological disease associated with celiac disease.

Cirrosis hepática criptogenética y mutaciones de factores protrombóticos: ¿una mera asociación?

Thrombin activation and microthrombosis of intrahepatic portal venules is a common feature in liver cirrhosis, due in part to relative protein C deficiency and altered coagulation-anticoagulation-fibrinolysis balance. Extension of this microthrombotic process to larger portal vessels explains the increased incidence of portal vein thrombosis in liver cirrhosis. Thrombin not only leads to thrombosis, but also activates liver stellate cells and promotes fibrogenesis. Also, ischemia associated with thrombosis up-regulates the expression and secretion of growth factors involved in fibrogenesis. The coincidence in a given patient of prothrombotic mutations, such as factor V Leiden or PAI-1 polymorphisms, can accelerate the fibrogenetic process. We hereby present two cases of liver cirrhosis in which etiologic evaluation was negative except for the finding of a factor V Leiden mutation in one case and the 4G/5G PAI polymorphism in the second case. These observations support the hypothesis that these mutations may be involved in the etiology of some cases of cirrhosis, or, at least, accelerate the evolution of the disease. It is therefore convenient to search for the presence of prothrombotic mutations in patients with cryptogenetic cirrhosis.

En la cirrosis hepática es frecuente que se produzca activación de la trombina y microtrombosis en las raicillas de la vena porta intrahepática, en parte debido al déficit de proteína C, y en parte a alteración del equilibrio coagulación-anticoagulación-fibrinólisis. Por eso hay una incidencia aumentada de trombosis portal. La trombina no solo puede generar la formación de un trombo, sino que puede activar a las células estrelladas y estimular la fibrogénesis. Además, la isquemia asociada a la trombosis puede promover la síntesis de factores de crecimiento involucrados en la fibrogénesis. La coincidencia en un mismo paciente de mutaciones protrombóticas, como factor V Leiden o polimorfismos del PAI-1, puede acelerar todo este proceso. Presentamos dos casos de cirrosis criptogenética en los que los únicos factores identificables capaces de causar fibrogénesis acelerada fueron mutaciones del factor V y del PAI-1. Estas observaciones, además de apoyar la hipótesis de que las citadas mutaciones puedan por sí mismas llegar a provocar cirrosis, sugieren que es recomendable determinar si existen polimorfismos del factor V, PAI-1 y protrombina en el estudio de la cirrosis criptogenética.

Primary liposarcoma of the sigmoid presenting as colonic intussusception: a Case Report

Liposarcomas are malignant soft tissue neoplasms usually located in the retroperitoneum, head, neck and extremities. Although secondary invasion of the gastrointestinal tract by retroperitoneal sarcomas is frequent, primary involvement is uncommon. We report a young patient with Crohn's disease in remission presenting with intussusception of the colon due to a primary liposarcoma of the sigmoid. Emergency resection confirmed the diagnosis. The patient remains in remission after five years. This represents the youngest diagnosis of liposarcoma to date and the first occurring in the sigmoid. We also highlight the concomitant diagnosis of Crohn's disease.

Severe ischemic colitis following olanzapine use: a Case Report

Ischemic colitis is the most common subtype of intestinal ischemia usually resulting from vasospasm, vessel occlusion or mesenteric hypoperfusion. Neuroleptics have seldom been linked to ischemic colitis by blocking peripheral anticholinergic and antiserotonergic receptors inducing severe gastrointestinal paresis. We report a young patient with severe ischemic colitis requiring surgery due to necrosis of the bowel. After exclusion of other potential causes, olanzapine was admitted as the cause of ischemia. Clinicians should be aware of how to recognize and treat the potentially life-threatening effects of neuroleptics.

Enfermedad de Crohn metastásica en pediatría

Introduction: Metastatic Crohn's disease (MCD) is an extraintestinal manifestation of Crohn's disease, with biopsy as fundamental diagnostic tool. There are few References to MCD in children, with a 0.5-1% estimated incidence in adults. There is no consensus about its therapeutic approach. We describe our diagnostic and therapeutic experience in MCD. Case Reports: Four cases of MCD are described in our Pediatric Gastroenterology Unit in a tertiary care hospital. The age at diagnosis was between 7 and 13 years. Lesions appeared before the diagnosis of Crohn's disease in three of them, and during the course of the disease in another one, with genital location in three patients and bilateral pretibial region in the other. All four cases demonstrated non-caseificant granulomas on biopsy. Only two patients used exclusive enteral nutrition therapy with complete resolution, while other two cases received a combination of therapies (corticosteroids, azathioprine, tacrolimus, infliximab and adalimumab) because of recurrence. Only one case required surgery after poor clinical control. Discussion: The MCD is infrequent but must always be included in the differential diagnosis of cutaneous lesions in Crohn's disease, considering it could be the debut of the disease. We will rely on biopsy anyway for definitive diagnosis. In this series the genital region is verified as the most commonly affected in children. The therapeutic approach does not differ from the management of intestinal involvement.

Introducción: la enfermedad de Crohn metastásica (ECM) constituye una manifestación extraintestinal de la enfermedad de Crohn, siendo fundamental la biopsia para su diagnóstico. Existen referencias escasas a ECM en la edad pediátrica, y en adultos se estima una incidencia del 0,5-1%. No hay consenso sobre su abordaje terapéutico. Nuestro objetivo es describir nuestra experiencia diagnóstica y terapéutica en ECM. Caso clínico: se describen 4 casos de ECM en seguimiento en una Unidad de Gastroenterología Infantil en un hospital pediátrico de tercer nivel. Edades al diagnóstico entre 7 y 13 años. Las lesiones aparecieron antes del diagnóstico de enfermedad de Crohn (EC) en tres de ellos y durante la evolución de la enfermedad en otro. Localización genital en tres pacientes y en región pretibial bilateral en el otro. Todos demostraron granulomas no caseificantes en la biopsia. Dos pacientes precisaron únicamente nutrición enteral exclusiva, observándose resolución completa, mientras que otros dos recibieron terapias combinadas (corticoides, azatioprina, tacrolimus, infliximab y adalimumab) por recurrencia. Solo un caso requirió cirugía por mal control clínico. Discusión: la ECM es una entidad rara aunque siempre debemos incluirla en el diagnóstico diferencial de las lesiones cutáneas en enfermedad de Crohn, teniendo en cuenta que puede ser el debut de la enfermedad. Nos basaremos en la biopsia en cualquier caso para el diagnóstico definitivo. En esta serie se verifica la región genital como la más habitual en niños. El abordaje terapéutico no difiere del manejo de la afectación intestinal.

Primary anorectal malignant melanoma: an uncommon anorectal pathology

Asymptomatic bronchial aspiration of capsule endoscope: a significant complication

Whipple's disease under the vision of capsule endoscopy