Revista Española de Enfermedades Digestivas

PPIs: between overuse and underprescription when really necessary

Reasons for initiation of proton pump inhibitor therapy for hospitalised patients and its impact on outpatient prescription in primary care

Background: Proton-pump-inhibitors are often prescribed unnecessarily in hospitals, which in turn induces their prescriptions after discharge. Objective: To evaluate patients starting treatment with proton-pump-inhibitors during hospitalisation and proportion of inappropriate prescriptions. Patient risk factors and whether initiation in hospital induced their continuation in ambulatory care were also analyzed. Methods: An observational, cross-sectional study in a tertiary hospital (1350 beds) was carried out on the first Tuesday in February 2015. Pharmacists screened admitted patients treated with proton-pump-inhibitors using an electronic prescription program (FarmaTools®-5.0). They also checked patients' home medications before admission by accessing a primary care program (Horus®). Authorized indications according to Spanish-Medicines-Agency and those recommended in Spanish-Clinical-Practice-Guidelines were considered appropriate. Hospital-medical-records were checked to know whether proton-pump-inhibitors were prescribed at discharge. Results: Three hundred seventy nine patients were analysed. Two hundred ninety four of them were prescribed proton-pump-inhibitors (77.6%). Treatment was initiated during admission for 143 patients (48.6%, 95% CI: 42.8-54.5). Of them, 91 (63.6%, 95% CI: 55.2-71.5) were inappropriate, mainly due to its inclusion unnecessarily in protocols associated with surgeries or diseases (56 cases of 91, 61.5%). Additional inappropriate indications were surgical stress ulcer prophylaxis for surgeries without bleeding risks (19.8%) and polypharmacy without drugs that increase the risk of bleeding (18.7%). Of 232 discharge reports assessed, in 153 (65.9%, 95% CI: 59.5-72), proton-pump-inhibitor continuation was recommended, of them, 51 (33.3%) were initiated at admission. Conclusion: In hospitalized patients there is a high prevalence of prescription of proton-pump-inhibitors unnecessarily. The superfluous use is often associated with the prescription of treatment protocols. Those treatments started in the hospital generally did not contribute to over-use existing primary care, most of them were removed at discharge.

Role of colonic microbiota in colorectal carcinogenesis: a systematic review

Background and aim: The human colonic mucosa is populated by a wide range of microorganisms, usually in a symbiotic relation with the host. Sometimes this balance is lost and a state of dysbiosis arises, exposing the colon to different metabolic and inflammatory stimuli (according to the microbiota's changing profile). Recent findings lead to hypothesize that this unbalance may create a subclinical pro-inflammatory state that increases DNA mutations and, therefore, colorectal carcinogenesis. In this article we aim to systematically review the scientific evidence regarding colonic microbiota and its role in colorectal carcinogenesis. Methods: Systematic review of PubMed searching results for original articles studying microbiota and colorectal cancer until November 2014. Results: Thirty-one original articles studied the role of colon microbiota in colorectal carcinoma including both human and animal studies. Different and heterogeneous methods were used and different bacteria were considered. Nevertheless, some bacteria are consistently augmented (such as Fusobacteria, Alistipes, Porphyromonadaceae, Coriobacteridae, Staphylococcaceae, Akkermansia spp. and Methanobacteriales), while other are constantly diminished in colorectal cancer (such as Bifidobacterium, Lactobacillus, Ruminococcus, Faecalibacterium spp., Roseburia, and Treponema). Moreover, bacteria metabolites amino acids are increased and butyrate is decreased throughout colonic carcinogenesis. Conclusion: Conclusive evidence shows that colorectal carcinogenesis is associated with microbial dysbiosis. This information may be used to create new prophylactic, diagnostic and therapeutic strategies for colorectal cancer.

Neomycin and bacitracin reduce the intestinal permeability in mice and increase the expression of some tight-junction proteins

Background: Tight-junction (TJ) proteins regulate paracellular permeability. Gut permeability can be modulated by commensal microbiota. Manipulation of the gut microbiota with antibiotics like bacitracin and neomycin turned out to be useful for the treatment of diarrhoea induced by Clostridium difficile or chemotherapy drugs. Aim: To evaluate the effects of the microbiota depletion evoked by the oral administration of neomycin and bacitracin on the intestinal permeability and expression of TJ proteins in mice. Methods: Mice received neomycin and bacitracin orally for 7 days. Intestinal permeability was measured by the fluorescein-isothiocyanate-dextran (FITC-dextran) method. The gene expression of TJ proteins in the intestine was determined by real time-PCR. Results: FITC-dextran levels in serum were reduced by half in antibiotic-treated mice, indicating a reduction of intestinal permeability. Antibiotics increased the expression of zonula occludens 1 (ZO-1), junctional adhesion molecule A (JAM-A, and occludin in the ileum and ZO-1, claudin-3, and claudin-4 in the colon. Conclusion: The combination of neomycin and bacitracin reduce intestinal permeability and increase the gene expression of ZO-1, junctional adhesion molecule A (JAM-A), and occludin in the ileum and ZO-1, claudin-3, and claudin-4 in the colon.

Antecedentes: las proteínas de unión estrecha (UE) regulan la permeabilidad paracelular. La permeabilidad intestinal puede estar modulada por la microbiota comensal. Las manipulaciones de la microbiota intestinal con antibióticos como la bacitracina y neomicina han resultado ser útiles para el tratamiento de la diarrea inducida por Clostridium difficile o los fármacos quimioterápicos. Objetivos: evaluar los efectos de la depleción de la microbiota mediante la administración oral de bacitracina y neomicina sobre la permeabilidad intestinal y la expresión de las proteínas de UE en ratón. Métodos: los ratones recibieron por vía oral la combinación de neomicina y bacitracina durante 7 días. La permeabilidad intestinal se cuantificó con el método del dextrano marcado con isotiocianato de fluoresceína (FITC-dextrano). La expresión de las proteínas de UE en el intestino se determinó mediante PCR a tiempo real. Resultados: los niveles de FITC-dextrano en suero se redujeron a la mitad en los ratones tratados con antibióticos, indicando una reducción de la permeabilidad intestinal. Los antibióticos incrementaron la expresión de zónula occludens 1 (ZO-1), molécula de adhesión de unión A (JAM-A) y ocludina en íleon y de ZO-1, claudina-3 y claudina-4 en colon. Conclusiones: la combinación de neomicina y bacitracina reduce la permeabilidad intestinal e incrementa la expresión de ZO-1, JAM-A y ocludina en íleon y ZO-1, claudina-3 y claudina-4 en colon.

Small bowel obstruction due to laparoscopic barbed sutures: an unknown complication?

Background: In recent years there has been an increasing uptake in the use of barbed sutures, particularly in minimally invasive and laparoscopic procedures where they may reduce operating time and improve surgical efficiency. However, little is known about the adverse events associated with these new materials and concerns have arisen regarding their safety in certain procedures. Methods: We performed a search of electronic databases (PubMed, EMBASE, and Cochrane Database). We reveal up to 15 cases of small bowel obstruction (SBO) complicating laparoscopic pelvic surgery that have been reported to date adding two cases of SBO in our own practice following the use of barbed sutures in laparoscopic operations, both requiring surgical re-intervention in the early post-operative period. Results: Fifteen similar cases of small bowel obstruction were identified, all of which occurred in patients undergoing surgery below the transverse colon. Surgical re-intervention was required in all cases although 60% of these were performed laparoscopically. Conclusions: These cases highlight that although barbed sutures provide an attractive means to allow easier and faster laparoscopic suturing, they should be used carefully in inframesocolic surgery and the suture end cut and buried to avoid inadvertent attachment to the small bowel or its mesentery. Barbed suture entanglement should be considered as an uncommon yet potentially serious differential cause for SBO presenting in the early period after laparoscopic surgery where a barbed suture has been used.

**Efficacy of metronidazole versus placebo in pain control after hemorrhoidectomy: results of a controlled clinical trial**

Introduction: Hemorrhoidal disease occurs in 50% of people aged > 40 years and is the most common reason for anorectal surgery. Pain is the main complication. Multiple topical and systemic drugs have been investigated for pain control, but there is no ideal treatment. Metronidazole has been shown to decrease postoperative pain but is not used widely. Objective: To evaluate the effect of oral metronidazole versus placebo and to assess postoperative pain following hemorrhoidectomy. Material and methods: Controlled clinical trial in adult patients who underwent elective hemorrhoidectomy for grade III/IV hemorrhoids. Patients were assigned to receive metronidazole (500 mg q8 h orally; study group, SG) or placebo (control group, CG) for 7 days after surgery. Pain was assessed using a visual analog scale after surgery. Analgesic administration (time and use of analgesics) and resumption of daily life activities were also assessed. Results: Forty-four patients were included, 22 in each group. Postoperative pain differed significantly between the SG and CG at 6 h (3.86 ± 0.56, 6.64 ± 1.49), 12 h (5.59 ± 1.33, 8.82 ± 0.79), 24 h (6.86 ± 1.49, 9.73 ± 0.45), day 4 (5.32 ± 2.10, 9.50 ± 0.59), day 7 (3.14 ± 1.03, 7.36 ± 1.39), and day 14 (2.14 ± 0.46, 5.45 ± 1.29). The first analgesia dose was required at 21.27 ± 5.47 h in the CG and 7.09 ± 2.36 h in the SG (p < 0.05), the time of analgesic use was 6.86 ± 1.61 days in the CG and 13.09 ± 2.48 days in the SG (p < 0.05), and resumption of daily activities occurred at 7.59 ± 1.56 days in the CG and 14.73 ± 3.76 days in the SG (p < 0.05). Conclusion: Oral administration of metronidazole is effective in pain management after hemorrhoidectomy.

Introducción: la enfermedad hemorroidal se presenta en 50% de adultos mayores a 40 años, siendo la principal indicación de cirugía anorrectal y el dolor su principal complicación. Múltiples fármacos, tópicos y sistémicos, se han investigado para control del dolor, no obstante no existe un tratamiento ideal. El metronidazol ha demostrado disminuirlo, pero su uso no se ha generalizado. Objetivos: evaluar el efecto de administración oral de metronidazol versus placebo en el control del dolor post-hemorroidectomía. Material y métodos: ensayo clínico controlado en pacientes adultos con hemorroides grado III/IV. Los del grupo de estudio (GE) recibieron metronidazol 500 mg oral cada 8 horas por 7 días y los del grupo control (GC) placebo. Se evaluó dolor postquirúrgico con escala visual análoga (EVA), consumo de analgésicos y reincorporación al trabajo. Resultados: se incluyeron 44 pacientes, 22 en cada grupo, sin diferencias en la distribución demográfica. La evaluación del dolor postquirúrgico fue de 3,86 ± 0,56 y 6,64 ± 1,49 para GE y GC a las 6 h, de 5,59 ± 1,33 y 8,82 ± 0,79 a las 12 h, 6,86 ± 1,49 y 9,73 ± 0,45 a las 24 h, 5,32 ± 2,10 y 9,50 ± 0,59 al cuarto, 3,14 ± 1,03 y 7,36 ± 1,39 al séptimo, 2,14 ± 0,46 y 5,45 ± 1,29 al 14 día, significativo a favor del GE. La primera dosis analgésica se requirió a las 7,09 ± 2,36 h en el GE y 21,27 ± 5,47 horas en el GC (p < 0,05); tiempo del consumo de analgésicos 6,86 ± 1,61 y 13,09 ± 2,48 días (p < 0,05) y reincorporación al trabajo a los 7,59 ± 1,56 y 14,73 ± 3,76 días (p < 0,05). Conclusiones: la administración oral de metronidazol es eficaz para el control del dolor post-hemorroidectomía.

The intestinal barrier function and its involvement in digestive disease

The gastrointestinal mucosal surface is lined with epithelial cells representing an effective barrier made up with intercellular junctions that separate the inner and the outer environments, and block the passage of potentially harmful substances. However, epithelial cells are also responsible for the absorption of nutrients and electrolytes, hence a semipermeable barrier is required that selectively allows a number of substances in while keeping others out. To this end, the intestine developed the "intestinal barrier function", a defensive system involving various elements, both intra- and extracellular, that work in a coordinated way to impede the passage of antigens, toxins, and microbial byproducts, and simultaneously preserves the correct development of the epithelial barrier, the immune system, and the acquisition of tolerance against dietary antigens and the intestinal microbiota. Disturbances in the mechanisms of the barrier function favor the development of exaggerated immune responses; while exact implications remain unknown, changes in intestinal barrier function have been associated with the development of inflammatory conditions in the gastrointestinal tract. This review details de various elements of the intestinal barrier function, and the key molecular and cellular changes described for gastrointestinal diseases associated with dysfunction in this defensive mechanism.

La superficie de la mucosa del tracto gastrointestinal está revestida de células epiteliales que establecen una barrera efectiva, mediante uniones intercelulares, entre el medio interno y el medio externo, impidiendo el paso de sustancias potencialmente nocivas. Sin embargo las células epiteliales también son responsables de la absorción de nutrientes y electrolitos, por lo que se requiere una barrera semipermeable que permita el paso selectivo a ciertas sustancias, mientras que evite el acceso a otras. Para ello, el intestino ha desarrollado la "función barrera intestinal", un sistema defensivo compuesto por diferentes elementos, tanto extracelulares como celulares, que actúan de forma coordinada para impedir el paso de antígenos, toxinas y productos microbianos y, a la vez, mantiene el correcto desarrollo de la barrera epitelial, el sistema inmunitario y la adquisición de tolerancia hacia los antígenos de la dieta y la microbiota intestinal. La alteración de los mecanismos que componen la función barrera favorece el desarrollo de respuestas inmunitarias exageradas, y, aunque se desconoce su implicación exacta, la alteración de la función barrera intestinal se ha asociado al desarrollo de enfermedades inflamatorias en el tracto digestivo. En esta revisión se detallan los diferentes elementos que componen la función barrera intestinal y las alteraciones moleculares y celulares más características descritas en enfermedades digestivas asociadas a la disfunción de este mecanismo de defensa.

Comb sign in intestinal obstruction secondary to desmoplastic reaction due to an ileal neuroendocrine tumor

**Direct parasitologial diagnosis of infection with Hysterothylacium aduncum in a patient with epigastralgia**

Ectopic pancreas in gallbladder: clinical significance, diagnostic and therapeutic implications

Ectopic or heterotopic pancreas is defined as the presence of pancreatic tissue in an anatomical place not related to the pancreas, being it most frequent locations the stomach and small bowel. Its finding in the gallbladder is exceptional. Since the first case was reported by Otschkin in 1916, about 30 cases have been described in literature. We report the case of a 43 years-old male patient who had an urgent laparoscopic cholecystectomy with the diagnosis of acute cholecystitis, which pathological study showed the existence of chronic cholecystitis with heterotopic pancreatic tissue in the gallbladder wall.

Páncreas ectópico o heterotópico se define como la presencia de tejido pancreático en una localización anatómica que no tiene relación con el páncreas, siendo sus localizaciones más frecuentes el estómago y el intestino delgado. Su hallazgo en la vesícula biliar es excepcional. Desde que Otschkin publicara el primer caso en 1916, alrededor de 30 más han sido descritos en la literatura. Presentamos el caso de un paciente varón de 43 años al que se le realizó una colecistectomía laparoscópica urgente con diagnóstico de colecistitis aguda cuyo estudio histopatológico demostró la existencia de colecistitis crónica con tejido pancreático heterotópico en la pared de la vesícula biliar.

Granulomatous appendicitis as an uncommon cause of abdominal pain: description of a case

Splenic rupture after colorectal cancer screening

Infarction of the greater omentum: case report

Unusual course of epiploic appendicitis

Case report: Amyand's hernia, diagnosis to consider in a routine procedure

Massive gastrointestinal pneumatosis in a patient with celiac disease and superior mesenteric artery syndrome

Tratamiento diurético en la ascitis del paciente cirrótico