A concise review of opioid-induced esophageal dysfunction: is this a new clinical entity?

Opioids have become the most widely prescribed analgesics in Western countries. Opioid-induced bowel dysfunction is a widely known adverse effect, with constipation the most common manifestation. Most of the opioid-related effects occur in the stomach, small intestine, and colon and have been widely studied. However, the effects related to esophageal motility are less known. Recently published retrospective studies have suggested that long-term use of opioids can cause esophageal motility dysfunction, reflecting symptoms similar to motility disorders, such as achalasia and functional esophagogastric junction outflow obstruction. The most common manometric findings, as reported in the literature, for patients with opioid-induced dysphagia undergoing long-term therapy with these drugs are impaired lower esophageal sphincter relaxation, high amplitude/velocity, and simultaneous esophageal waves, higher integrated relaxation pressure, lower distal latency, and the esophageal contractility can be normal, hypercontractile, or premature. Based on these studies, a new clinical entity known as opioid-induced esophageal dysfunction has been postulated. For these patients, the diagnostic method of choice is high-resolution manometry, although other causes should be ruled out through endoscopy or Computed Tomography (CT). The best therapeutic option for these patients is withdrawal of the opioid; however, this is not always possible, and other options need to be investigated, such as pneumatic dilation and botulinum toxin injection, considering the risks versus the benefits.

Evaluation of esophagogastric junction relaxation by 4-second Integrated Relaxation Pressure in achalasia using High Resolution Manometry with water-perfused catheters.

BACKGROUND: Relaxation of the esophagogastric junction (EGJ) is now evaluated calculating 4-second integrated relaxation pressure (4-s IRP) by high resolution manometry (HREPT). Solid-state catheters have been used to define abnormal values. Our aim was to evaluate 4-s IRP in esophageal achalasia using HREPT with perfused catheters. METHODS: From June 2009 to June 2013, 936 HREPT studies have been performed in our unit. Of these, 194 patients having treated achalasia were excluded. Control group was constituted by 695 patients without achalasia, and 47 patients with untreated achalasia constituted the study group. HREPT was performed with water-perfused catheters. To establish the cut-off value for 4-s IRP that better discriminate patients with achalasia from all other patients, a receiver operating characteristic (ROC) analysis was performed. KEY RESULTS: Twenty three of 47 achalasia patients (49%) showed a 4-s IRP under 15 mmHg; and seven (15%) had a value under modified Chicago criteria. A cut-off value for 4-s IRP of 6.5 mmHg, calculated by ROC analysis, highly discriminates achalasia from the rest of the patients and especially from scleroderma patients (area under the curve: 0.997, 95% CI: 0.995-1.000; p < 0.001). CONCLUSIONS & INFERENCES: Cut-off values for 4-s IRP defined using HREPT with solid-state catheters are not adequate for diagnosing esophageal achalasia with water-perfused systems. A lower value, i.e., 6.5 mmHg, is suggested for this equipment. The diagnostic criteria of esophageal achalasia should be modified for HREPT performed with water-perfused systems.

Structured management strategy based on the Gastro-oesophageal Reflux Disease (GERD) Questionnaire (GerdQ) vs. usual primary care for GERD: pooled analysis of five cluster-randomised European studies.

BACKGROUND: Response to treatment among primary care patients with gastro-oesophageal disease (GERD) is variable. AIM: The GERD Management Project (GMP) evaluated the effectiveness of a structured management approach to GERD vs. standard treatment (usual care). METHODS: Data from five cluster-randomised clinical trials in adult primary care patients with symptoms of GERD were pooled. The structured pathway was based on the self-administered GERD Questionnaire (GerdQ) and was compared with standard treatment. RESULTS: 1734 patients were enrolled (structured treatment, n=834; standard treatment, n=900). The difference in the mean GerdQ score change from baseline favoured the structured pathway (-0.61; 95% CI: -0.88, -0.34; p<0.001). The odds ratio for an indication for treatment revision at the end of follow-up (structured vs. standard treatment) was 0.39 (95% CI: 0.29, 0.52; p=0.001). CONCLUSIONS: Management of primary care patients with GERD can be improved by systematic stratification of patients using a patient management tool such as the GerdQ.

Normal values in ambulatory oesophageal pH monitoring at two levels in Spain.

AIM: Upper oesophageal pH monitoring may play a significant role in the study of extra-oesophageal GERD, but limited normal data are available to date. Our aim was to develop a large series of normal values of proximal oesophageal acidification. METHODS: 155 healthy volunteers (74 male) participated in a multi-centre national study including oesophageal manometry and 24 hours oesophageal pH monitoring using two electrodes individually located 5 cm above the LOS and 3 cm below the UOS. RESULTS: 130 participants with normal manometry completed all the study. Twelve of them were excluded for inadequate pH tests. Twenty-seven subjects had abnormal conventional pH. The remaining 91 subjects (37 M; 18-72 yrs age range) formed the reference group for normality. At the level of the upper oesophagus, the 95th percentile of the total number of reflux events was 30, after eliminating the meal periods 22, and after eliminating also the pseudo-reflux events 18. Duration of the longest episodes was 5, 4 and 4 min, respectively (3.5 min in upright and 0.5 min in supine). The upper limit for the percentage of acid exposure time was 1.35, 1.05 and 0.95%, respectively. No reflux events were recorded in the upper oesophagus in 8 cases. CONCLUSION: This is the largest series of normal values of proximal oesophageal reflux that confirm the existence of acid reflux at that level in healthy subjects, in small quantity and unrelated to age or gender. Our data support the convenience of excluding pseudo-reflux events and meal periods from analysis.

[Post-transplant renal tumors: a report of three cases]. / Diagnostic des tumeurs du greffon rénal: à propos de trois cas.

We report three cases of primary renal tumors occurring on post-transplant kidneys, after a delay of 4, 8 and 12 years respectively following transplantation in a population of 1134 post kidney transplant followed at our institution. All three tumors underwent early detection because of the yearly ultrasound evaluation recommended for all post kidney transplant patients. The diagnosis was suggested by CT in all three cases but confirmed by preoperative percutaneous biopsy in two cases. The final pathology results confirmed two cases of clear cell renal carcinomas and one case of oncocytoma. Tumorectomy was undertaken for all three patients with successful results in two cases and return to hemodialysis in the third patient with a 4 cm tumor with mass effect on the collecting system.

Disease-specific health-related quality of life in patients with esophageal achalasia before and after therapy.

BACKGROUND: To evaluate disease-specific health-related quality of life (HRQoL) in patients with symptomatic esophageal achalasia before and after therapy. METHODS: Symptoms and disease-specific HRQoL were evaluated before and 3 months after therapy. Therapy selection, either dilatation or myotomy, depended exclusively on the opinion of the physician on charge of the patient. Symptom severity was graded from 0 to 3, using a scoring system. A disease-specific questionnaire for achalasia developed and validated in Spanish language with 18 items and four subscales (AE-18) was used to evaluate HRQoL. Changes after therapy in HRQoL and its association with clinical improvement were analyzed. KEY RESULTS: Sixty-five patients were prospectively included in eight hospitals in Spain. Of them, 47 were treated with dilatation, and 18 with laparoscopic Heller myotomy. After therapy, AE-18 global and subscales scores improved significantly. Changes in HRQoL were associated with improvement in symptoms. An important improvement in symptoms (>or=50%) was needed to obtain a minimal clinically important improvement (>or=20%) in HRQoL. CONCLUSIONS & INFERENCES: Disease-specific HRQoL improves in patients with symptomatic achalasia after therapy with dilatation or myotomy. The degree of improvement of HRQoL depends on the degree of improvement of esophageal symptoms.

Outcome of non-variceal acute upper gastrointestinal bleeding in patients with antithrombotic therapy.

AIM: To determine the influence of antithrombotic therapy upon the course of non-variceal upper gastrointestinal bleeding (UGB). METHODS: A cohort study was made of consecutive patients admitted to hospital with non-variceal UGB. Three cohorts were defined: patients receiving vitamin K antagonists (AC); patients with antiplatelet treatment (AP), and patients with neither of these treatments (noACAP) as control group. Outcome was assessed by: (a) number of days in hospital; (b) mortality rate; (c) need for urgent surgery, and (d) rebleeding. The measure of the association between antithrombotic therapy and the course of UGB was adjusted for confounders (age, sex, comorbidity, and the use of NSAIDs and PPIs at the time of UGB presentation). RESULTS: A total of 392 consecutive patients were included: 43 were AC, 107 AP, and 242 noACAP patients. There were no significant differences among groups in terms of rebleeding (AC 11.6%, AP 7.5%, NoACAP 9.1%), the need for urgent surgery (AC 2.3%, AP 1.9%, NoACAP 1.2%) or mortality rate (AC 4.7%, AP 5.6%, NoACAP 5.8%). The number of days in hospital was greater in the AC cohort (4.81 more days; 95% CI 2.83-6.79, p < 0.001). After adjusting for age and comorbidity, the increase in days in hospital among the AC patients was 3.24 days (95% CI 1.22-5.26). CONCLUSIONS: Neither anticoagulation nor antiplatelet treatment exerts an influence upon the course of non-variceal UGB. Nevertheless, anticoagulation is associated with a longer hospital stay. This is partially explained by the older age and increased comorbidity of the patients subjected to such treatment.

Nuevos retos en la formación especializada. I. Perfil y evaluación del Jefe de Estudios. II. Plan de calidad de la docencia en los centros sanitarios. III. Evaluación del residente. Propuesta de evaluación de las rotaciones / New challenges in specialised training. I. Profile and appraisal of the Head of Studies. II. Plan for improving teaching quality in health centres. III. Evaluation of house officers. Proposal for the evaluation of rotations

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Change over time of bowel habit in irritable bowel syndrome: a prospective, observational, 1-year follow-up study (RITMO study).

BACKGROUND: Evolution of bowel habit in irritable bowel syndrome (IBS) is not well known. AIM: To evaluate the change over time of bowel habit in IBS patients followed-up during 1 year. METHODS: Five hundred and seventeen patients with IBS were prospectively included in an observational study with five evaluations over a 1-year period. Symptoms were recorded daily in diary cards during four 4-week periods along the study. Bristol Stool Scale (BSS) was used to define bowel habit. RESULTS: Four-hundred patients completed the study. Rome II showed low-moderate agreement (42%) with BSS to define bowel habit. Frequency of constipation and diarrhoea showed little changes throughout the study. Over 50% of the patients had the same bowel habit when each diary was compared with the next one. A third of patients maintained the same habit throughout the study. Most changes occurred from/to mixed or unsubtyped IBS. Only 14% of cases changed from constipation to diarrhoea or vice versa. This change was associated to female gender (OR: 2.65). CONCLUSIONS: The frequency of constipation and diarrhoea remains relatively stable over time. Changes in IBS subtypes are common, but changes between constipation and diarrhoea are rare. Alternating IBS is more frequent in women.

Healthcare seeking for constipation: a population-based survey in the Mediterranean area of Spain.

BACKGROUND: The use of healthcare resources for the management of constipation is not well-known. AIM: To analyse healthcare seeking for constipation, defined by three different criteria, and its related factors and to assess the frequency of use of laxatives, suppositories and enemas for the treatment of constipation. METHODS: A cross-sectional study in the general community. A questionnaire comprising 21-items was developed and delivered by mail to a random sample of 506 subjects aged 18-65 years, and belonging to a Spanish population. RESULTS: Seeking of health care was high in the sample (16%) and was similar for all definitions of constipation (over 40% of constipated subjects). It was associated with female gender, a higher educational level and two symptoms, such as prolonged defecation and abdominal pain. A 14% of the sample used laxatives, and about a 25% of constipated subjects used laxatives at least once a week. Utilization was more frequent in women, with no differences by age group. CONCLUSIONS: Chronic constipation is a problem that causes an important consumption of resources in our setting, derived from laxative use and the seeking of medical help to combat the problem. The use of these resources is higher in women.

Predictive factors of irritable bowel syndrome improvement: 1-year prospective evaluation in 400 patients.

BACKGROUND: The natural history of the irritable bowel syndrome is poorly understood. AIM: To assess the clinical course of the irritable bowel syndrome and the factors that might predict it. METHODS: An observational prospective study, involving 400 irritable bowel syndrome patients meeting Rome II criteria. Symptoms were recorded in a diary over four non-consecutive months (1, 4, 7 and 10). Demographic data, associated disorders, psychological status and health-related quality of life were obtained. RESULTS: At 1-year follow-up, half of the patients and half of their physicians considered irritable bowel syndrome to have improved, but improvement was minor. Diary data showed that, according to the type of symptom, improvement was small and quite different: diarrhoea in 19% of patients, abdominal pain frequency in 26%, constipation in 33% and abdominal pain intensity in 60%. Factors related to improvement at one year were: severe symptoms and poor health-related quality of life at first visit, irritable bowel syndrome-constipation, good improvement at 3 months, anxiety/depression, stress, symptoms related to meals and absence of comorbidity. By multivariate logistic regression, predictors were: severe basal symptoms and good improvement at 3 months (OR:CI 95%, 1.32:1.09-1.59 and 4.44:2.81-7.05). CONCLUSIONS: At 1-year follow-up, half the patients and their physicians considered the irritable bowel syndrome to have had some improvement but, symptom diaries demonstrated that improvement was small and heterogeneous. Severe basal symptoms and improvement at 3 months were related to better prognosis.

[Factors influencing the decision to administer systemic corticosteroids in Crohn's disease]. / Factores que influyen en la decisión de administrar corticoides sistémicos en la enfermedad de Crohn.

INTRODUCTION: Crohn's disease shows periods of exacerbation and remission. Corticosteroids are the most frequently used drugs in exacerbations of disease activity. The objective of this study is to determine which clinical and laboratory parameters are associated with the therapeutic decision to administer corticosteroids during the course of the disease. MATERIAL AND METHOD: Two-hundred seven consecutive visits made by 62 patients with Crohn's disease were selected from a database. Data from visits in which corticosteroid administration was initiated (n = 65) were compared with those from visits in which this decision was not made (n = 142). Univariate and multivariate (logistic regression) analyses were performed. The results are expressed as odds ratio (OR) with 95% confidence interval (95% CI). RESULTS: In the univariate analysis statistically significant differences were found between groups in localization, maintenance treatment, Crohn's Disease Activity Index (CDAI) score, the presence of abdominal pain, mass, perianal disease, extraintestinal manifestations and all laboratory parameters (leukocytes, platelets, fibrinogen, erythrocyte sedimentation rate, C-reactive protein). In the multivariate analysis (with corticosteroid administration as the dependent variable) a statistically significant positive association was found between the decision to administer corticosteroids and mild (OR = 31.9; 95% CI, 6.6-154.1), moderate or severe (OR = 49.7; 95% CI, 6.1-401.3) CDAI, ileocolic localization (OR = 4.8; 95% CI, 1-22.1) and the presence of perianal disease (OR = 7.4; 95% CI, 1.5-35.9), while a negative association was found with maintenance treatment with immunosuppressant drugs (OR = 0.05; 95% CI, 0.30-0.008). The laboratory variables positively associated with corticosteroid administration were C-reactive protein and leukocyte count. CONCLUSION: The variable with greatest predictive value for corticosteroid prescription is the CDAI score, although other clinical and laboratory variables not included in this index are also associated with corticosteroid administration. There is a negative association between the use of immunosuppressive drugs and corticosteroid prescription.

Diagnostic value of symptoms in patients with suspected upper digestive tract disease.

OBJECTIVE: to develop a predictive model based on clinical data for patients with suspected upper digestive tract disease. PATIENTS AND METHODS: forty-seven clinical data were obtained before endoscopy from 283 patients with suspected upper digestive disease (153 men; mean age 55 years, limits 17-92 years). A clinical prediction of diagnosis was made before endoscopy. On the basis of the endoscopic findings, the patients were divided into three diagnostic groups: absence of significant disease (group I), significant benign disease (group II) and malignant disease (group III). The probability rate of belonging to each one of the three groups was obtained for each patient by using Bayes' theorem. RESULTS: the endoscopic findings were classified according to their clinical importance: 121 patients (43%) belonged to group I, 137 (48%) were included in group II; and 25 (9%) in group III. The clinical prediction correctly classified 61% of the patients (group I: 56%, group II: 62% and group III: 76%) The coincidence between prediction obtained using Bayes' theorem and the actual diagnosis was 61% (group I: 65%, group II: 51%, group III: 92%). The predictive model was useful to confirm or not the clinical prediction. CONCLUSION: objective analysis of clinical data can be useful to support clinical judgment, mainly in patients with neoplasia. However, the model is not adequate to improve indication of upper endoscopy since many patients are misclassified.

Valor diagnóstico de los síntomas en pacientes con sospecha de enfermedad del tracto digestivo superior / Diagnoctic value of symptoms in patients with suspected upper digestive tract disease

Objetivo: desarrollar un modelo objetivo, predictivo del diagnóstico endoscópico a partir del análisis de los síntomas en pacientes con sospecha de enfermedad del tracto digestivo superior. Pacientes y métodos: se recogieron prospectivamente 47 variables en cada uno de los 283 pacientes estudiados (153 hombres; media de edad 55 años, límites 17-92 años) a los que se había indicado una endoscopia digestiva alta. Previamente se emitió un juicio predictivo clínico sobre cuál era el diagnóstico más probable. Los hallazgos endoscópicos se agruparon en función de su trascendencia clínica en tres categorías diagnósticas que fueron: ausencia de enfermedad trascendente (grupo I), enfermedad trascendente benigna (grupo II) y enfermedad maligna (grupo III). A partir de las 23 variables más discriminativas se obtuvo en cada paciente la probabilidad de que perteneciera a cada uno de los tres grupos diagnósticos, mediante el teorema de Bayes. Resultados: pertenecieron al grupo I, 121 pacientes (43 por ciento), 137 (48 por ciento) al grupo II; y 25 (9 por ciento) al grupo III. El juicio clínico clasificó correctamente al 61 por ciento de los pacientes (grupo I: 56 por ciento, grupo II: 62 por ciento y grupo III: 76 por ciento). La coincidencia entre el modelo objetivo y el diagnóstico real fue del 61 por ciento (grupo I: 65 por ciento, grupo II: 51 por ciento, grupo III: 92 por ciento). El modelo predictivo se demostró útil para confirmar o no el juicio predictivo clínico, previamente emitido por el médico. Conclusión: el análisis objetivo de los datos clínicos puede servir de apoyo al juicio clínico, emitido por el médico, especialmente en pacientes con neoplasia. Sin embargo, muchos pacientes son clasificados erróneamente con este análisis lo que le resta utilidad para mejorar la indicación de una endoscopia digestiva alta (AU)

Cough reflex testing with inhaled capsaicin in the study of chronic cough.

OBJECTIVES: To assess the utility of capsaicin test in the differential diagnosis of non-productive causes of chronic cough and to examine the effects of treatment on this reflex. PARTICIPANTS: 86 healthy volunteers and 101 patients with chronic cough: asthma (n: 54) gastroesophageal reflux (n: 35) and post-nasal drip syndrome (n: 12). DESIGN: Prospective intervention trial. Spirometry, bronchoprovocation test with histamine (PC20), and cough challenge with ascending concentrations of capsaicin (0.49-500 microM) were initially performed in all subjects. Patients were treated for 3 months according to the origin of the cough. Concentrations that elicited two (C2) and five or more coughs (C5) were determined before and after treatment. RESULTS: In healthy subjects, cough sensitivity to capsaicin was not influenced by gender or smoking status; however, women with chronic cough were more sensitive to cough challenge than men. C2 and C5 were significantly lower in patients with asthma or gastroesophageal reflux than in post-nasal drip syndrome. No significant correlation was observed between the capsaicin cough threshold and PC20. Cough sensitivity did not improve significantly in most patients with asthma or gastroesophageal reflux despite adequate medical treatment during 3 months. Discriminative value of capsaicin test to differentiate healthy subjects from patients with asthma or reflux was poor. CONCLUSIONS: Cough sensitivity to inhaled capsaicin is a safe and reproducible tool in the study of chronic cough. However, its usefulness for the management and differential diagnosis is limited.

[Dynamic ultrasonography in the diagnosis of gallbladder dysfunction: reliability of a simple method with easy clinical application]. / Ultrasonografía dinámica en el diagnóstico de la disfunción vesicular: fiabilidad de un método sencillo de fácil aplicación clínica.

AIMS: Although the results of dynamic ultrasonography (DUS) are similar to those of dynamic cholescintigraphy (DCS) in the study of gallbladder function, the methodology required for this technique is laborious and sometimes complex. The aim of this study was to investigate the reliability of a simple method of DUS to evaluate gallbladder function using DCS as a reference. PATIENTS AND METHODS: Gallbladder function was studied using DUS and DCS in 80 consecutive patients with clinical findings compatible with gallbladder dysfunction. For DUS the ellipsoid method was used with measurement of three gallbladder diameters (transversal, longitudinal and anteroposterior) in basal conditions and after applying a cholecystokinetic stimulus (meal test); gallbladder emptying of less than 50% was considered abnormal. In DCS intravenous cholecystokinin (CCK) (0.40 IDU/kg in 20 minutes) was used as stimulus and an ejection fraction < or = 40% was considered abnormal. RESULTS: In 15 patients (19%; 95% CI, 11-29%) abnormal gallbladder response was found using DUS. The ejection fraction in the entire group of patients studied was 48 26.2%. Ejection fraction was abnormal in 41 patients (51%; 95% IC, 40-63%) with a value of 25 8.5% and was normal in 39 patients (49%; 95% IC, 40-63%) with a value of 71.5 14.5%. The correlation coefficient between the values of gallbladder emptying calculated with DUS and the ejection fraction obtained with DCS was 0.199 (p = 0.079). When patients were divided according to gallbladder emptying measured by DUS and the ejection fraction obtained with DCS the concordance was very low (k = 0.065; EE = 0.085). CONCLUSIONS: DUS performed using a simple technique lacks diagnostic value in gallbladder dysfunction when DCS is taken as a reference test

Efectos secundarios del tratamiento con azatioprina en la enfermedad inflamatoria crónica intestinal / Adverse effects of azathioprine in the treatment of inflammatory bowel disease

Objetivo: conocer el tipo, frecuencia y perfil temporal de efectos secundarios en nuestra serie de pacientes afectos de enfermedad inflamatoria intestinal tratados con azatioprina, o 6-mercaptopurina.Pacientes y método: de 92 pacientes consecutivos tratados con azatioprina, se analizó una serie de 70 casos (55 enfermedad de Crohn, 14 colitis ulcerosa y 1 colitis indeterminada). Resultados: se contabilizaron 23 acontecimientos adversos en 21 pacientes: hematológicos 11,4 por ciento, gastrointestinales 11,4 por ciento, infecciones 7,1 por ciento y pancreatitis 2,8 por ciento. La prevalencia de efectos secundarios entre pacientes con colitis ulcerosa fue significativamente superior a la de los pacientes con enfermedad de Crohn (57,8 frente a 21,8 por ciento) (p=0,02). No hubo diferencias en cuanto a su aparición según edad, sexo y localización de la enfermedad. Los efectos gastrointestinales y la pancreatitis aparecieron precozmente (< 6 meses). La toxicidad hematológica se presentó entre los 3 meses y 4 años. Su aparición tardía no se relacionó con los niveles de TMPT y sí su aparición precoz. Todas las infecciones aparecieron de forma tardía (entre 8 meses y 5 años). El fármaco fue retirado definitivamente a causa de los afectos adversos en 9 casos (12,8 por ciento).Conclusiones: la frecuencia de efectos secundarios en nuestra serie es similar a la descrita en la literatura. En casi la mitad de los pacientes que los presentan obligan a la retirada del fármaco. Destaca su mayor frecuencia en la colitis ulcerosa. La gran variabilidad en cuanto al momento de presentación obliga a realizar un seguimiento clínico-analítico frecuente y continuado (AU)

Adverse effects of azathioprine in the treatment of inflammatory bowel disease.

OBJECTIVE: To know the type, frequency and time course for the occurrence of adverse events in our series of patients with inflammatory bowel disease treated with azathioprine or 6-mercaptopurine. PATIENTS AND METHOD: 92 consecutive patients were treated with azathioprine. 70 of them (55 Crohn's disease, 14 ulcerative colitis and 1 undetermined colitis) were suitable for analysis. RESULTS: We observed 23 adverse reactions in 21 patients. Adverse events were as follows: haematological 11.4%, digestive intolerance 11.4%, infection 7.1%, and pancreatitis 2.8%. The prevalence was increased among ulcerative colitis patients (57.8 vs. 21.8%) (p = 0.02). There were no statistical differences in the prevalence of adverse events respective of the age, gender or location of disease. Digestive intolerance and pancreatitis occurred within the first 6 months of therapy, whereas haematological side effects occurred between 3 months and 4 years after therapy onset. Early occurrence (but not late occurrence) was associated with thiopurine methyltransferase (TMPT) activity levels. All infections took place between 8 months and 5 years of treatment. Azathioprine was definitively withdrawn due to side effects in 9 cases (12.8%). CONCLUSIONS: The frequency of adverse events in our study is similar to that reported in previous studies. Azathioprine withdrawal is required in almost half of the cases because of toxicity. Frequency of side effects is increased in patients with ulcerative colitis. The variability in time course makes clinical-biological monitoring mandatory.

Prevalence of gastroesophageal reflux in asthma.

A high prevalence of gastroesophageal reflux disease (GER) in asthma patients has been shown in several reports from North America and Europe. However, no data from Southern Europe are available. This paper evaluates the prevalence of abnormal reflux in asthmatics, the pattern of acid reflux when present, and the relationship between asthma and GER. Eighty-one consecutive ambulatory patients with clinically stable asthma (41 women; median age 40 years, range 17-69 years) were prospectively evaluated. All patients had a thorough digestive history; baseline pulmonary function studies, including bronchoprovocation methacholine test; and ambulatory 24-hr esophageal pH monitoring. Reflux symptoms were present in 40 patients (49%). Twelve patients had abnormal GER as defined by pH testing, giving a prevalence rate of 15% (95% confidence interval 8%-24%). The presence of acid reflux was not associated with a more severe respiratory disease. Abnormal GER seems not to be a clinically significant problem in many patients with asthma in our area.

Efficacy and safety of cardiomyotomy in patients with achalasia after failure of pneumatic dilatation.

In patients with achalasia, it has been suggested that pneumatic dilatation could make cardiomyotomy more difficult to perform, diminishing its efficacy and safety. Our aim was to evaluate the efficacy and safety of elective cardiomyotomy after failure of pneumatic dilatation in achalasia. During 14 years, 32 of 276 consecutive patients with achalasia have been operated on because of failure of dilatation therapy. Twenty patients have been followed-up for at least one year after surgery. After failure of dilatation, Heller's cardiomyotomy and 180 degrees anterior fundoplication were performed. Clinical status was evaluated before and after surgery. Lower esophageal sphincter pressure and esophageal body basal pressure were measured by manometry, esophageal diameter by barium meal, and gastroesophageal reflux by endoscopy and 24-hr esophageal pH monitoring. No technical difficulties were found during operation. Postoperative morbidity was infrequent and mortality was absent. Cardiomyotomy improved clinical status in 19 of 20 patients. The results of surgery were considered excellent or good in 16 patients (80%; CI: 56-94%). The pressure of the lower esophageal sphincter was significantly reduced, falling in most patients to under 10 mm Hg. Gastroesophageal reflux appeared after surgery in eight patients, four of them with endoscopic esophagitis, but it was controlled in all patients with medical therapy. In conclusion, cardiomyotomy is a safe and effective therapy in achalasia after failed pneumatic dilatation.