Immunomodulatory Therapy Does Not Increase the Risk of Cancer in Persons With Inflammatory Bowel Disease and a History of Extracolonic Cancers.

OBJECTIVES: Immunosuppressant therapies (IMTs; thiopurines, anti-tumor necrosis factor agents) may influence the immunologic control of cancer and might facilitate the spread and recurrence of cancer. This study assesses the impact of the use of IMTs on the development of incident cancers (recurrent or new) in patients with inflammatory bowel disease (IBD) and a history of malignancy. METHODS: Patients with IBD included in the ENEIDA registry with a history of cancer without being exposed to IMTs were identified and retrospectively reviewed and compared regarding further treatment with IMTs or not by means of a log-rank test. RESULTS: Overall, 520 patients with previous extracolonic cancer naive to IMTs before the diagnosis of cancer were identified. Of these, 146 were subsequently treated with IMTs (exposed), whereas 374 were not (nonexposed). The proportion of patients with incident cancers was similar in both exposed (16%) and nonexposed (18%) patients (P = 0.53); however, there was more than a 10-year difference in the age at index cancer between these 2 groups. Cancer-free survival was 99%, 98%, and 97% at 1, 2, and 5 years in exposed patients, and 97%, 96%, and 92% at 1, 2, and 5 years in non-exposed patients, respectively (P = 0.03). No differences in incident cancer rates were observed between exposed and nonexposed patients when including only those who were exposed within the first 5 years after cancer diagnosis. DISCUSSION: In patients with IBD and a history of cancer not related to immunosuppression, the use of IMTs is not associated with an increased risk of new or recurrent cancers even when IMTs are started early after cancer diagnosis.

Long-Term Safety of In Utero Exposure to Anti-TNFα Drugs for the Treatment of Inflammatory Bowel Disease: Results from the Multicenter European TEDDY Study.

OBJECTIVES: The long-term safety of exposure to anti-tumor necrosis factor (anti-TNFα) drugs during pregnancy has received little attention. We aimed to compare the relative risk of severe infections in children of mothers with inflammatory bowel disease (IBD) who were exposed to anti-TNFα drugs in utero with that of children who were not exposed to the drugs. METHODS: Retrospective multicenter cohort study. Exposed cohort: children from mothers with IBD receiving anti-TNFα medication (with or without thiopurines) at any time during pregnancy or during the 3 months before conception. Non-exposed cohort: children from mothers with IBD not treated with anti-TNFα agents or thiopurines at any time during pregnancy or the 3 months before conception. The cumulative incidence of severe infections after birth was estimated using Kaplan-Meier curves, which were compared using the log-rank test. Cox-regression analysis was performed to identify potential predictive factors for severe infections in the offspring. RESULTS: The study population comprised 841 children, of whom 388 (46%) had been exposed to anti-TNFα agents. Median follow-up after delivery was 47 months in the exposed group and 68 months in the non-exposed group. Both univariate and multivariate analysis showed the incidence rate of severe infections to be similar in non-exposed and exposed children (1.6% vs. 2.8% per person-year, hazard ratio 1.2 (95% confidence interval 0.8-1.8)). In the multivariate analysis, preterm delivery was the only variable associated with a higher risk of severe infection (2.5% (1.5-4.3)). CONCLUSIONS: In utero exposure to anti-TNFα drugs does not seem to be associated with increased short-term or long-term risk of severe infections in children.

Abdominal accommodation induced by meal ingestion: differential responses to gastric and colonic volume loads.

BACKGROUND: Using an experimental model of colonic gas infusion, we previously showed that the abdominal walls adapt to its content by an active phenomenon of abdominal accommodation. We now hypothesized that abdominal accommodation is a physiological phenomenon, and aimed to confirm that it can be induced by ingestion of a meal; a secondary aim was to determine whether the response to gut filling is region-specific. METHODS: In healthy subjects (n = 24) a nutrient test meal was administered until tolerated at a rate of 50 mL min(-1). Electromyographic (EMG) activity of the anterior wall (upper and lower rectus, external and internal oblique) was measured via four pairs of surface electrodes, and EMG activity of the diaphragm via intraluminal electrodes on an esophageal tube. To address the secondary aim, the response to gastric filling was compared with that induced by colonic filling (1440 mL 30 min(-1) anal gas infusion; n = 8). KEY RESULTS: Participants tolerated 927 ± 66 mL of meal (450-1500 mL). Meal ingestion induced progressive diaphragmatic relaxation (EMG reduction by 16 ± 2%; P < 0.01) and selective contraction of the upper abdominal wall (24 ± 2% increase in activity of the upper rectus and external oblique; P < 0.01 for both), with no significant changes in the lower rectus (4 ± 2%) or internal oblique (5 ± 3%). Colonic gas infusion induced a similar response, but with an overall contraction of the anterior wall. CONCLUSIONS & INFERENCES: Meal ingestion induces a metered and region-specific response of the abdominal walls to accommodate the volume load. Abnormal abdominal accommodation could be involved in postprandial bloating.

Efficacy of infliximab rescue therapy in patients with chronic refractory pouchitis: a multicenter study.

BACKGROUND: Despite medical therapy, 30% of patients with ulcerative colitis (UC) need to undergo surgery. Around 50% of patients with proctocolectomy with ileal pouch-anal anastomosis (IPAA) develop complications of the pouch. Clinical evidence for the use of infliximab (IFX) in refractory pouchitis is limited. The aim of this study was to report efficacy of IFX in these patients. METHODS: A retrospective, multicenter study was designed. Patients older than 18 years with chronic refractory pouchitis treated with IFX (5 mg/kg) were included. Short-term IFX efficacy was evaluated at week 8 and mid-term efficacy at weeks 26 and 52. Complete response was defined as cessation of diarrhea and urgency and partial response as marked clinical improvement but persisting symptoms. The modified Pouchitis Disease Activity Index (mPDAI) without endoscopy was calculated when available. RESULTS: Thirty-three consecutive UC patients with chronic refractory pouchitis were included (18 male, mean age 45 years, range 21-67). At week 8, 21% patients achieved complete response and 63% showed partial clinical response. At weeks 26 and 52, 33% and 27% achieved complete response and 33% and 18% showed partial clinical response, respectively. Thirteen patients (39%) withdrew treatment (four for lack of efficacy, four for loss of response and five for adverse events). None of the potential factors analyzed had an influence on response to IFX. CONCLUSIONS: IFX was effective in the short- and mid-term in patients with chronic refractory pouchitis. However, medication had to be discontinued in a high number of patients.

Accommodation of the abdomen to its content: integrated abdomino-thoracic response.

BACKGROUND: We previously showed that changes in intra-abdominal content induce a volume-dependent muscular response of the anterior abdominal wall and the diaphragm. We aimed to determine the contribution of the thorax to abdominal accommodation and the influence of the intra-abdominal expansion rate. METHODS: Gas (1440 mL total load) was infused into the colon of nine healthy subjects, while abdomino-thoracic perimeters (by tape measure), electromyography (EMG) activity of the diaphragm (via six ring electrodes over an esophageal tube in the hiatus), intercostals and anterior abdominal wall (via five pairs of surface electrodes) and the position of the diaphragm by ultrasonography were measured. Infusion rates of 24, 48, and 96 mL min(-1) were tested on separate days. KEY RESULTS: Gas infusion induced anterior abdominal wall contraction (18 ± 1% EMG increment; P < 0.001) with relatively modest girth increment (4.9 ± 0.9 mm; P = 0.001), diaphragmatic relaxation (by 15 ± 1%; P < 0.001) with cephalad displacement (by 23 ± 6 mm; P = 0.005), and intercostal contraction (by 19 ± 2%; P < 0.001) with increased thoracic perimeter (by 2.0 ± 0.5 mm; P = 0.009). Responses were similar with the three infusion rates. CONCLUSIONS & INFERENCES: Accommodation of intra-abdominal loads involves a volume-related integrated abdomino-thoracic response regardless of the expansion rate.

Meta-analysis: predictors of rebleeding after endoscopic treatment for bleeding peptic ulcer.

BACKGROUND: Determining the risk of rebleeding after endoscopic therapy for peptic ulcer bleeding (PUB) may be useful for establishing additional haemostatic measures in very high-risk patients. AIM: To identify predictors of rebleeding after endoscopic therapy. METHODS: Bibliographic database searches were performed to identify studies assessing rebleeding after endoscopic therapy for PUB. All searches and data abstraction were performed in duplicate. A parameter was considered to be an independent predictor of rebleeding when it was detected as prognostic by multivariate analyses in ≥2 studies. Pooled odds ratios (pOR) were calculated for prognostic variables. RESULTS: Fourteen studies met the prespecified inclusion criteria. Pre-endoscopic predictors of rebleeding were: (i) Haemodynamic instability: significant in 9 of 13 studies evaluating the variable (pOR: 3.30, 95% CI: 2.57-4.24); (ii) Haemoglobin value: significant in 2 of 10 (pOR: 1.73, 95% CI: 1.14-2.62) and (iii) Transfusion: significant in two of six (pOR not calculable). Endoscopic predictors of rebleeding were: (i) Active bleeding: significant in 6 of 12 studies (pOR: 1.70, 95% CI: 1.31-2.22); (ii) Large ulcer size: significant in 8 of 12 studies (pOR: 2.81, 95% CI: 1.98-4.00); (iii) Posterior duodenal ulcer location: significant in four of eight studies (pOR: 3.83, 95% CI: 1.38-10.66) and (iv) High lesser gastric curvature ulcer location: significant in three of eight studies (pOR: 2.86; 95% CI: 1.69-4.86). CONCLUSIONS: Major predictors for rebleeding in patients receiving endoscopic therapy are haemodynamic instability, active bleeding at endoscopy, large ulcer size, ulcer location, haemoglobin value and the need for transfusion. These risk factors may be useful for guiding clinical management in patients with PUB.

Impaired intestinal gas propulsion in manometrically proven dysmotility and in irritable bowel syndrome.

BACKGROUND: Intestinal manometry is the current gold standard for diagnosing small bowel dysmotility; however, the functional significance of abnormal manometry is unknown. Our aim was to determine whether, and to what extent, intestinal gas propulsion is impaired in patients with manometrically proven dysmotility compared with healthy controls and patients with IBS. METHODS: Clearance and tolerance of a jejunal gas load (12 mL min(-1) for 2 h) were measured in 15 patients with severe abdominal symptoms and intestinal dysmotility evidenced by manometry, 15 patients with IBS and 15 healthy subjects. Thereafter, the effect of neostigmine (0.5 mg i.v. bolus) vs placebo (i.v. saline) was tested in six dysmotility patients. KEY RESULTS: After 2-h gas infusion, patients with dysmotility developed significantly more gas retention (717 +/- 91 mL) than IBS patients (372 +/- 82 mL; P = 0.0037) and healthy subjects (17 +/- 67 mL; P < 0.0001 vs dysmotility; P = 0.0060 vs IBS). Despite the greater retention in dysmotility patients, abdominal perception (2.5 +/- 0.6 score) and distension (7 +/- 2 mm girth increment) were similar to IBS (3.9 +/- 0.6 score and 7 +/- 2 mm, respectively). In dysmotility patients, neostigmine produced immediate clearance of gas, and by 30 min had reduced gas retention (by -552 +/- 182 vs 72 +/- 58 mL after saline; P = 0.008), abdominal symptoms (by -0.8 +/- 0.3 score vs 0.3 +/- 0.2 after saline; P = 0.019) and distension (girth change -5 +/- 1 mm; P = 0.003 vs-2 +/- 2 mm after saline). CONCLUSION & INFERENCES: Patients with manometric dysmotility have markedly impaired intestinal gas propulsion. In IBS patients, impaired gas propulsion is less pronounced but associated with concomitant sensory dysfunction and poor tolerance of gas retention.

Meta-analysis: high-dose proton pump inhibitors vs. standard dose in triple therapy for Helicobacter pylori eradication.

BACKGROUND: The evidence on whether high-dose proton pump inhibitors (PPIs) increase cure rates of Helicobacter pylori treatment has not been previously assessed. AIM: To evaluate the evidence on the usefulness of high-dose PPI in standard triple therapy by performing a systematic review and a meta-analysis. METHODS: A systematic search was performed in multiple databases and in the abstracts submitted to the Digestive Diseases Week, the European Helicobacter Study Group congress and the United European Gastroenterology Week. Randomized trials comparing a standard dose of a PPI with high-dose PPI both twice a day in triple therapy combining a PPI plus clarithromycin and either amoxicillin or metronidazole were selected. Relative risk (RR) and 95% confidence intervals (95% CIs) for all comparisons were calculated using Review Manager. RESULTS: Six studies fulfilled the inclusion criteria. All used triple therapy for 7 days. A mean intention-to-treat cure rate of 82% was achieved with high-dose PPI and one of 74% with standard dose (RR: 1.09; 95% CI: 1.01-1.17). Subgroup analysis showed that the maximum increase was observed when the PPI compared were omeprazole 20 mg or pantoprazole 40 mg vs. esomeprazole 40 mg. CONCLUSION: High-dose PPI seems more effective than standard-dose for curing H. pylori infection in 7-day triple therapy.

Intestinal tone and gas motion.

The intestine propels and evacuates large gas loads without detectable phasic contractions by manometry. We hypothesized that intestinal gas motion is produced by changes in gut tone and capacitance. In 13 healthy subjects, changes in duodenal tone were measured by a barostat during continuous perfusion of lipids (Intralipid, 1 kcal min(-1)) into the duodenum for 60 min. In separate groups, the effects of jejunal gas infusion (N2, CO2 and O2 in venous proportions at 12 mL min(-1) starting after 15 min lipid perfusion) and sham infusion were tested. Gas outflow was collected continuously via an intrarectal cannula. Duodenal lipid perfusion produced a rapid duodenal relaxation (volume increased by 48 +/- 18%; P < 0.01 vs basal). Gas infusion increased gas evacuation (184 +/- 59 mL), and this was associated with a tonic contraction of the duodenum (R = 0.86; P < 0.01) that completely reverted the lipid-induced duodenal relaxation (volume decreased by 42 +/- 13%; P < 0.05). During sham infusion only 52 +/- 28 mL of gas were evacuated (P < 0.05 vs gas infusion), and the duodenum remained relaxed due to the effect of lipids (0 +/- 1% volume reduction; ns). In conclusion, intestinal gas propulsion and clearance is associated with a tonic contraction of the gut wall and reduced gut capacitance.

[Epidemiological study of colorectal cancer in Zamora (Spain): a comparison between the years 1996 and 2003]. / Estudio epidemiológico del cáncer colorrectal en la provincia de Zamora: comparación entre los años 1996 y 2003.

INTRODUCTION: Colorectal cancer (CRC) is one of the most frequent tumors in Western countries. In Spain, widely different rates have been reported for distinct regions. AIM: To determine the epidemiological characteristics of CRC in the province of Zamora in 1996 and 2003 and to identify possible variations in these characteristics in each of these two years. MATERIAL AND METHODS: We performed a descriptive, retrospective study of all cases of CRC diagnosed in the Complejo Asistencial de Zamora in 1996 and 2003. RESULTS: In 1996, 146 patients were diagnosed with CRC, representing an unadjusted and adjusted incidence of 70.85 and 49.40 cases per 10(5) inhabitants. In 2003, 173 patients were diagnosed, representing an unadjusted and adjusted incidence of 86.89 and 58.12 cases per 105 inhabitants. The mean age at diagnosis was 72.08 years in 1996 and 71.15 years in 2003. The mean time to diagnosis was 3.37 months in 1996 and 4.11 in 2003. The mean time to diagnosis in 1996 was 4.35 months in rectal tumors and 2.87 months in colon tumors (p = 0.013). In 2003, the mean time to diagnosis was 4.70 months in rectal tumors and 3.84 months in colon tumors (p = 0.0749). The mean time to diagnosis was 3.56 and 3.83 months in patients living in urban areas and was 3.24 and 4.35 months in those living in rural areas in 1996 and 2003, respectively. More than 65% of the neoplasms were located in the rectum and sigmoid colon, with no differences between the two years. In 1996, 46.1% of the tumors were stage III or IV at diagnosis while in 2003, this percentage increased to 50.9%. In both years, the four basic health areas with the highest rates within the province were Aliste, Carbajales, Carballeda and Corrales. CONCLUSION: CRC is a highly frequent disease in the province of Zamora, especially in some of the western regions. The incidence of CRC was higher in 2003 than in 1996. Most of the tumors were located in the rectum and sigmoid colon. The time from symptom onset to diagnosis was prolonged. A high percentage of tumors were diagnosed in advanced stages.

Efficacy and safety of argon plasma coagulation for the treatment of hemorrhagic radiation proctitis.

OBJECTIVE: To evaluate the efficacy, safety and medium-/long-term clinical course of patients undergoing endoscopic treatment with argon plasma coagulation for hemorrhagic radiation proctopathy. DESIGN: Descriptive, retrospective study with medium- and long-term follow-up. PATIENTS, MATERIAL AND METHODS: Ten patients were treated with argon plasma coagulation for hemorrhagic radiation proctopathy between July 1998 and February 2003. Inclusion criteria were: evidence of chronic rectal bleeding, consistent endoscopic findings, and absence of any other cause of hematochezia after a comprehensive ano-rectal examination and complete colonoscopy. The equipment used was a standard colonoscope, an argon delivery unit, an argon plasma coagulation probe 1.5 mm in internal diameter, and a high-frequency electrosurgical generator. Consecutive treatment sessions were programmed whenever it was considered necessary until all mucosal lesions had been treated. Clinical and evolutive follow-up was performed with a focus on tolerance, efficacy, and potential argon plasma coagulation-related complications. Data were updated by personal or telephonic interview. RESULTS: In all patients, chronic rectal bleeding stopped after the last treatment session. The mean number of treatment sessions to stop symptoms was 1.7. Mean follow-up was 31.1 months. All sessions were well tolerated, similarly to standard rectoscopy. In one case a recurrence of rectal bleeding was observed four months later, which required two repeat sessions. Four patients were anemic at inclusion. Three of them reported a resolved anemia at the end of the study. No delayed argon plasma coagulation-related complications such us ulcers or strictures were seen. CONCLUSIONS: Argon plasma coagulation appears to be a useful, effective and safe treatment for rectal bleeding resulting from chronic radiation proctitis when compared to standard medical and endoscopic treatments. These successful outcomes seem to persist even after long-term follow-up.

[Eosinophilic gastroenteritis: clinical spectrum of the same disease]. / Gastroenteritis eosinofílica: espectro clínico de una misma entidad.

Eosinophilic gastroenteritis is a condition of unknown etiopathogenesis and unusual description. Clinical symptoms are widely diverse ranging from mild episodes of abdominal discomfort to acute intestinal obstruction which leads occasionally to urgent surgical approach. This wide range of clinical possibilities seems to be secondary to the rate of eosinophilic infiltration of the bowel wall and the number of layers involved. We report two cases showing that anatomo-clinical variety and their therapeutic outcomes.

[Alendronate-induced hepatocellular lesion]. / Lesión hepatocelular inducida por alendronato.

Bisphosphonates are widely used in the treatment of metabolic bone disease. Bisphosphonate-induced hepatotoxicity is extremely infrequent. We present the case of a 76-year-old female patient with osteoporosis who was prescribed alendronate. A routine laboratory investigation carried out three months later revealed markedly elevated transaminase concentrations. Six weeks after withdrawal of treatment, laboratory parameters had returned to normal levels. We analyze this adverse reaction to alendronate as well as its possible pathogenic mechanisms.

[Acute cholestatic hepatitis induced by dextromethorphan]. / Hepatitis aguda colestásica inducida por dextrometorfano.

A case of a 68-years-old female who was symptomatically treated with the codeine analog dextromethorphan because of a flu-like syndrome is herein reported. Five days later, she developed a cholestatic syndrome without fever or abdominal pain. Dextrometorphan was withdrawn and a rapid clinical improvement was observed, associated with decreasing levels of biochemical markers of cholestasis. Normal values were reached two months later. This type of adverse drug reaction, its potential pathogenic mechanisms and the therapeutic consequences are discussed.

[Ischemic colitis associated with antithrombin deficiency]. / Colitis isquémica asociada a déficit de antitrombina III.

Colonic ischemia is one of the more common disorders of the colon in elderly people; the ischemic colitis can affect young people too. The splenic flexure, the descending colon and the sigmoid are the parts most commonly involved. Only in some cases it is possible to identify the specific cause of colonic ischemia. We report a case of ischemic colitis associated with antithrombin III deficiency.