Revista Española de Enfermedades Digestivas

Drugs prescription in patients with chronic liver disease: rules for adjusting doses and beyond

Drug dosage recommendations in patients with chronic liver disease

Chronic liver diseases (CLD) alter the kinetics of drugs. Despite dosage adjustment is based on Child-Pugh scores, there are no available recommendations and/or algorithms of reference to facilitate dosage regimens. A literature review about dose adjustment of the drugs from the hospital guide -which are included in the list of the WHO recommended drugs to be avoided or used with caution in patients with liver disease- was carried out. The therapeutic novelties from the last few years were also included. In order to do so, the summary of product characteristics (SPC), the database DrugDex-Micromedex, the WHO recommendations and the review articles from the last 10 years in Medline were reviewed. Moreover, the kinetic parameters of each drug were calculated with the aim of establishing a theoretical recommendation based on the proposal of Delcò and Huet. Recommendations for 186 drugs are presented according to the SPC (49.5%), DrugDex-Micromedex (26.3%) and WHO (18.8%) indications; six recommendations were based on specific publications; the theoretical recommendation based on pharmacokinetic parameters was proposed in four drugs. The final recommendations for clinical management were: dosage modification (26.9%), hepatic/analytical monitoring of the patient (8.6%), contraindication (18.8%), use with caution (19.3%) and no adjustment required (26.3%). In this review, specific recommendations for the practical management of patients with chronic liver disease are presented. It has been elaborated through a synthesis of the published bibliography and completed by following a theoretical methodology.

La insuficiencia hepática crónica produce alteraciones que afectan a la cinética de los medicamentos y a pesar de que su ajuste se basa en el índice Child-Pugh, no se disponen de recomendaciones y/o algoritmos de referencia que faciliten su dosificación. Se realizó una revisión bibliográfica de la dosificación en insuficiencia hepática crónica de los medicamentos de la guía del hospital incluidos en el listado de fármacos que la OMS recomienda no utilizar o utilizar con precaución en pacientes con enfermedad hepática, añadiendo las novedades terapéuticas de los últimos años. Para ello se revisaron las fichas técnicas, base DrugDex-Micromedex, recomendaciones de la OMS y artículos de revisión de los últimos 10 años en Medline; además, se calcularon los parámetros cinéticos de cada fármaco con el objeto de establecer una recomendación teórica basada en la propuesta de Delcò y Huet. Se presentan recomendaciones para 186 medicamentos, según lo indicado en la ficha técnica (49,5%), DrugDex-Micromedex (26,3%) y OMS (18,8%); 6 recomendaciones se realizaron en base a publicaciones específicas y en 4 fármacos se propuso la recomendación teórica basada en los parámetros farmacocinéticos. Las recomendaciones finales para el manejo clínico fueron de: modificación de dosis (26,9%), monitorización hepática/analítica del paciente (8,6%), contraindicación (18,8%), emplear con precaución (19,3%) y no requerir ajuste (26,3%). En esta revisión se presentan recomendaciones específicas para el manejo práctico del paciente con insuficiencia hepática crónica, obtenida mediante una síntesis de la bibliografía publicada y completada con aplicación de una metodología teórica.

**Self-expanding metal stents versus antrectomy for the palliative treatment of obstructive adenocarcinoma of the gastric antrum**

Background: gastric cancer patients are first diagnosed with an unresectable tumor in up to 40% of cases. Gastric outlet obstruction causes nausea, vomiting, dehydration and malnutrition. The aim of the study was to compare self-expanding metal stents to antrectomy and Roux-en Y gastrojejunostomy for palliation of obstructive adenocarcinoma of the gastric antrum. Methods: retrospective study in patients with obstructing cancer of the gastric antrum. Patients were divided into two groups: group A, underwent endoscopic placement of self-expanding metal stents and group B underwent surgical treatment with antrectomy and Roux-en Y gastrojejunostomy. Collected Data included: age, gender, performance status (Karnofsky's score), body mass index, histopathology, clinical stage (TNM classification), technical and clinical success of the procedure, time to oral intake, in-hospital stay, re-intervention rate, and complications related to the treatment and survival. Results: a total of 39 patients with gastric adenocarcinoma were included, 21 male and 18 female. Nineteen patients were assigned to group A and 20 patients to group B. There were no statistically significant differences between groups in regards to age, body mass index, Karnofsky's score and clinical stage. The technical and clinical success was similar for both groups. There was a statistically significant difference between groups favoring Self-expanding metal stent in time to oral intake (1 ± 0 vs. 4.9 ± 0.6 days, p = 0.0001) and in-hospital stay (0.94 ± 1.18 vs. 7.8 ± 7.7 days, p = 0.0005). We did not find statistically significant differences with regards to long-term survival. Conclusions: in patients with malignant gastric outlet obstruction due to gastric cancer, endoscopic palliation with self-expanding metal stents provide a shorter interval to oral intake, shorter in-hospital stay and lower rate of complications.

Introducción: los pacientes con cáncer gástrico tienen un tumor irresecable hasta en el 40% de los casos. La obstrucción de salida gástrica ocasiona vómito, deshidratación y desnutrición. El objetivo de este estudio fue comparar las prótesis metálicas autoexpandibles con la antrectomia en el tratamiento paliativo del adenocarcinoma obstructivo del antro gástrico. Método: estudio restrospectivo en pacientes con adenocarcinoma obstructivo del antro gástrico. Los pacientes fueron divididos en dos grupos: grupo A) sujetos que fueron tratados mediante prótesis metálica autoexpandible y grupo B) aquellos que fueron tratados mediante antrectomía y gastroyeyunoanastomosis en Y de Roux. Las variables recogidas fueron: edad, género, índice de masa corporal, histopatología, estadio clínico (TNM), estado general (escala de Karnofsky), días de estancia intrahospitalaria, necesidad de re-intervención, complicaciones relacionada con el tratamiento y sobrevida. Resultados: fueron incluidos 39 pacientes, 21 hombres y 18 mujeres. Diecinueve pacientes correspondieron al grupo A y 20 al grupo B. No hubo diferencias estadísticamente significativas con respecto a la edad, índice de masa corporal, calificación de Karnofsky y estadio clínico. El éxito técnico y clínico fue similar en ambos grupos. Hubo diferencia estadísticamente significativa entre ambos grupos, favoreciendo a las prótesis metálicas autoexpandibles en tiempo de inicio de la vía oral (1 ± 0 vs. 4,9 ± 0,6 días, p = 0,0001) y estancia intrahospitalaria (0,94 ± 1,18 vs. 7,8 ± 7,7 días, p = 0,0005). No encontramos diferencia estadísticamente significativa con respecto a la sobrevida entre los dos grupos. Conclusiones: en pacientes con obstrucción gástrica secundaria a cáncer gástrico avanzado, el tratamiento con prótesis metálicas autoexpandibles proporciona un intervalo mas corto para el inicio de la vía oral, una estancia intrahospitalaria mas corta y una frecuencia de complicaciones menor.

Is there still a role for intraoperative enteroscopy in patients with obscure gastrointestinal bleeding?

Background: in 21st century, endoscopic study of the small intestine has undergone a revolution with capsule endoscopy and balloon-assisted enteroscopy. The difficulties and morbidity associated with intraoperative enteroscopy, the gold-standard in the 20th century, made this technique to be relegated to a second level. Aims: evaluate the actual role and assess the diagnostic and therapeutic value of intraoperative enteroscopy in patients with obscure gastrointestinal bleeding. Patients and methods: we conducted a retrospective study of 19 patients (11 males; mean age: 66.5 ± 15.3 years) submitted to 21 IOE procedures for obscure GI bleeding. Capsule endoscopy and double balloon enteroscopy had been performed in 10 and 5 patients, respectively. Results: with intraoperative enteroscopy a small bowel bleeding lesion was identified in 79% of patients and a gastrointestinal bleed-ing lesion in 94%. Small bowel findings included: angiodysplasia (n = 6), ulcers (n = 4), small bowel Dieulafoy's lesion (n = 2), bleed-ing from anastomotic vessels (n = 1), multiple cavernous hemangiomas (n = 1) and bleeding ectopic jejunal varices (n = 1). Agreement between capsule endoscopy and intraoperative enteroscopy was 70%. Endoscopic and/or surgical treatment was used in 77.8% of the patients with a positive finding on intraoperative enteroscopy, with a rebleeding rate of 21.4% in a mean 21-month follow-up period. Procedure-related mortality and postoperative complications have been 5 and 21%, respectively. Conclusions: intraoperative enteroscopy remains a valuable tool in selected patients with obscure GI bleeding, achieving a high diagnostic yield and allowing an endoscopic and/or surgical treatment in most of them. However, as an invasive procedure with relevant mortality and morbidity, a precise indication for its use is indispensable.

**Laparoscopic versus open transhiatal esophagectomy for distal and junction cancer**

Background: the only curative treatment for esophageal cancer is surgical resection. This treatment is associated with a high morbidity rate and long in-hospital recovery period. Both transthoracic and transhiatal esophagectomies are performed worldwide. The transhiatal approach may reduce the respiratory infection rate in compromised patients with distal esophageal and gastro-esophageal (GE) cancers. Minimally invasive esophagectomy could further improve post-operative outcome. Two cohorts of laparoscopic and open transhiatal esophagectomy for cancer were compared for short- and long-term outcome. Methods: from January 2001 through December 2004, 50 patients who underwent laparoscopic transhiatal esophagectomy were compared to a historical group of 50 patients who had undergone open transhiatal esophagectomy between January 1998 and December 2000. Post-operative management was identical in both groups. Results: no significant differences were seen between the two groups with regard to baseline characteristics and oncological parameters including resection margin (R0 82 vs. 74%, p = 0.334) and 5-year survival. Operation time did not differ significantly between the groups. (300 vs. 280 min, p = 0.110). Median hospital stay and intensive care unit stay were significantly shorter in the laparoscopic group (13 vs. 16 days, p = 0.001 and 1 vs. 3 days, p = 0.000 respectively). Conclusion: minimally invasive transhiatal esophagectomy is feasible and has the same oncological outcome as open transhiatal esophagectomy. Faster recovery without a significant longer operation time could be the major benefit of the laparoscopic transhiatal approach. To our knowledge, this is the largest comparative study in literature comparing laparoscopic transhiatal with open transhiatal esophagectomy for cancers of distal and GE junction. Randomized trials are needed to further clarify the role of laparoscopic transhiatal approach for esophageal cancer.

Chronic hepatitis in man and in dog: a comparative update

Chronic hepatitis is a frequent pathologic condition encountered in both dogs and humans; however, in the latter etiologic factors are usually searched and found that allow targeted therapeutic approaches, whereas in dogs this is less frequent. This review will take into consideration chronic hepatitis in dogs, and discuss differences and similarities between the two species with respect to this disease.

Bronchobiliary fistula

Radiation enteritidis diagnosed by wireless capsule endoscopy

Herpetic esophagitis: a case report on an immunocompetent adolescent

Herpetic esophagitis in immunocompetent individuals is a rare entity that should be suspected clinically by an acute onset of symptoms, and without apparent cause of a symptomatic triad consisting on odynophagia, heartburn and fever. Its occurrence may be due to reactivation of a previous infection or less often a primary infection. Herpes simplex type 1 is the most common cause. Upper endoscopy establishes the diagnosis of suspicion of herpetic esophagitis. It also allows to take multiple biopsy samples and viral culture, leading to a definitive diagnosis. The severity of symptoms is related to the degree of oesophageal involvement. In immunocompromised patients treatment is indicated with acyclovir, but the indication in immunocompetent patients is controversial because the process is time, limited with a low probability of complications. We present a case of acute herpetic esophagitis in an immunocompetent host that debuted acutely with severe upper gastrointestinal tract symptoms, associated with an insidious and non-specific onset of flu-like symptoms. Endoscopic findings showed a severe involvement in the lower third of the oesophageal mucosa.

La esofagitis herpética en individuos inmunocompetentes, es una entidad rara, que debe de sospecharse clínicamente por el inicio agudo, y sin aparente causa, de una triada sintomática consistente en odinofagia, pirosis y fiebre. Su aparición puede deberse a una reactivación de una infección viral previa o con menor frecuencia a una primoinfección como tal, siendo el herpes tipo 1 el responsable en la mayoría de las ocasiones. La realización de una gastroscopia permite establecer el diagnóstico de sospecha de esta enfermedad y la toma de múltiples muestras para estudio histológico y cultivo viral, lo que lleva al diagnóstico definitivo. La severidad de los síntomas está en relación con el grado de afectación esofágica y aunque en los pacientes inmunocomprometidos el tratamiento con aciclovir está indicado, su administración en pacientes inmunocompetentes es controvertida puesto que se trata de un proceso autolimitado con baja probabilidad de complicaciones. Presentamos un caso de esofagitis herpética en un adolescente inmunocompetente, que debutó de forma aguda, con síntomas severos del tracto digestivo alto asociados a un comienzo insidioso que se atribuyó inicialmente a un proceso gripal. Los hallazgos endoscópicos muestran una importante y llamativa afectación de la mucosa esofágica en su tercio inferior y la toma de múltiples biopsias durante el procedimiento permitieron el diagnóstico.

Endoscopy in antiaggregated patients

Splenic rupture following diagnostic colonoscopy

**Relationship between H. pylori and hepatitis A virus infection**

The mathematics behind the twin-stoma gastrostomy

Doubts and similarities between Crohn's disease and Henoch-Schönlein purpura

Collagenous sprue with associated features of refractory celiac disease

Contribution of contrast enhanced sonography in the etiological diagnosis of focal splenic lesions