Carlos Guarner-Argente

Transfusion Strategies for Acute Upper Gastrointestinal Bleeding

BACKGROUND The hemoglobin threshold for transfusion of red cells in patients with acute gastrointestinal bleeding is controversial. We compared the efficacy and safety of a restrictive transfusion strategy with those of a liberal transfusion strategy. METHODS We enrolled 921 patients with severe acute upper gastrointestinal bleeding and randomly assigned 461 of them to a restrictive strategy (transfusion when the hemoglobin level fell below 7 g per deciliter) and 460 to a liberal strategy (transfusion when the hemoglobin fell below 9 g per deciliter). Randomization was stratified according to the presence or absence of liver cirrhosis. RESULTS A total of 225 patients assigned to the restrictive strategy (51%), as compared with 61 assigned to the liberal strategy (14%), did not receive transfusions (P<0.001) [corrected].The probability of survival at 6 weeks was higher in the restrictive-strategy group than in the liberal-strategy group (95% vs. 91%; hazard ratio for death with restrictive strategy, 0.55; 95% confidence interval [CI], 0.33 to 0.92; P=0.02). Further bleeding occurred in 10% of the patients in the restrictive-strategy group as compared with 16% of the patients in the liberal-strategy group (P=0.01), and adverse events occurred in 40% as compared with 48% (P=0.02). The probability of survival was slightly higher with the restrictive strategy than with the liberal strategy in the subgroup of patients who had bleeding associated with a peptic ulcer (hazard ratio, 0.70; 95% CI, 0.26 to 1.25) and was significantly higher in the subgroup of patients with cirrhosis and Child-Pugh class A or B disease (hazard ratio, 0.30; 95% CI, 0.11 to 0.85), but not in those with cirrhosis and Child-Pugh class C disease (hazard ratio, 1.04; 95% CI, 0.45 to 2.37). Within the first 5 days, the portal-pressure gradient increased significantly in patients assigned to the liberal strategy (P=0.03) but not in those assigned to the restrictive strategy. CONCLUSIONS As compared with a liberal transfusion strategy, a restrictive strategy significantly improved outcomes in patients with acute upper gastrointestinal bleeding. (Funded by Fundació Investigació Sant Pau; ClinicalTrials.gov number, NCT00414713.).

Step-up empiric elimination diet for pediatric and adult eosinophilic esophagitis: The 2-4-6 study

Background: Numerous dietary restrictions and endoscopies limit the implementation of empiric elimination diets in patients with eosinophilic esophagitis (EoE). Milk and wheat/gluten are the most common food triggers. Objective: We sought to assess the effectiveness of a step‐up dietary strategy for EoE. Methods: We performed a prospective study conducted in 14 centers. Patients underwent a 6‐week 2‐food‐group elimination diet (TFGED; milk and gluten‐containing cereals). Remission was defined by symptom improvement and less than 15 eosinophils/high‐power field. Nonresponders were gradually offered a 4‐food‐group elimination diet (FFGED; TFGED plus egg and legumes) and a 6‐food‐group elimination diet (SFGED; FFGED plus nuts and fish/seafood). In responders eliminated food groups were reintroduced individually, followed by endoscopy. Results: One hundred thirty patients (25 pediatric patients) were enrolled, with 97 completing all phases of the study. A TFGED achieved EoE remission in 56 (43%) patients, with no differences between ages. Food triggers in TFGED responders were milk (52%), gluten‐containing grains (16%), and both (28%). EoE induced only by milk was present in 18% and 33% of adults and children, respectively. Remission rates with FFGEDs and SFGEDs were 60% and 79%, with increasing food triggers, especially after an SFGED. Overall, 55 (91.6%) of 60 of the TFGED/FFGED responders had 1 or 2 food triggers. Compared with the initial SFGED, a step‐up strategy reduced endoscopic procedures and diagnostic process time by 20%. Conclusions: A TFGED diet achieves EoE remission in 43% of children and adults. A step‐up approach results in early identification of a majority of responders to an empiric diet with few food triggers, avoiding unnecessary dietary restrictions, saving endoscopies, and shortening the diagnostic process.

The role of a computed tomography-based image registered navigation system for natural orifice transluminal endoscopic surgery: a comparative study in a porcine model.

BACKGROUND AND STUDY AIMS Most natural orifice transluminal endoscopic surgery (NOTES) procedures have been performed in animal models through the anterior stomach wall, but this approach does not provide efficient access to all anatomic areas of interest. Moreover, injury of the adjacent structures has been reported when using a blind access. The aim of the current study was to assess the utility of a CT-based (CT: computed tomography) image registered navigation system in identifying safe gastrointestinal access sites for NOTES and identifying intraperitoneal structures. METHODS A total of 30 access procedures were performed in 30 pigs: anterior gastric wall (n = 10), posterior gastric wall (n = 10), and anterior rectal wall (n = 10). Of these, 15 procedures used image registered guidance (IR-NOTES) and 15 procedures used a blind access (NOTES only). Timed abdominal exploration was performed with identification of 11 organs. The location of the endoscopic tip was tracked using an electromagnetic tracking system and was recorded for each case. Necropsy was performed immediately after the procedure. The primary outcome was the rate of complications; secondary outcome variables were number of organs identified and kinematic measurements. RESULTS A total of 30 animals weighting a mean (± SD) of 30.2 ± 6.8 kg were included in the study. The incision point was correctly placed in 11 out of 15 animals in each group (73.3 %). The mean peritoneoscopy time and the number of properly identified organs were equivalent in the two groups. There were eight minor complications (26.7 %), two (13.3 %) in the IR-NOTES group and six (40.0 %) in the NOTES only group ( P = n. s.). Characteristics of the endoscope tip path showed a statistically significant improvement in trajectory smoothness of motion for all organs in the IR-NOTES group. CONCLUSION The image registered system appears to be feasible in NOTES procedures and results from this study suggest that image registered guidance might be useful for supporting navigation with an increased smoothness of motion.

Cytokine production in patients with cirrhosis and TLR4 polymorphisms.

AIM To analyze the cytokine production by peripheral blood cells from cirrhotic patients with and without TLR4 D299G and/or T399I polymorphisms. METHODS The study included nine patients with cirrhosis and TLR4 D299G and/or T399I polymorphisms, and 10 wild-type patients matched for age, sex and degree of liver failure. TLR4 polymorphisms were determined by sequence-based genotyping. Cytokine production by peripheral blood cells was assessed spontaneously and also after lipopolysaccharide (LPS) and lipoteichoic acid (LTA) stimulation. RESULTS Patients with TLR4 polymorphisms had a higher incidence of previous hepatic encephalopathy than wild-type patients (78% vs 20%, P = 0.02). Spontaneous production of interleukin (IL)-6 and IL-10 was lower in patients with TLR4 polymorphisms than in wild-type patients [IL-6: 888.7 (172.0-2119.3) pg/mL vs 5540.4 (1159.2-26053.9) pg/mL, P < 0.001; IL-10: 28.7 (6.5-177.1) pg/mL vs 117.8 (6.5-318.1) pg/mL, P = 0.02]. However, the production of tumor necrosis factor-α, IL-6 and IL-10 after LPS and LTA stimulation was similar in the two groups. CONCLUSION TLR4 polymorphisms were associated with a distinctive pattern of cytokine production in cirrhotic patients, suggesting that they play a role in the development of cirrhosis complications.

Endoscopic ultrasound and endoscopic retrograde cholangiopancreatography: Can they be successfully combined?

Endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) have much in common, including their main indications (biliopancreatic disorders), powerful therapeutic capacities and a steep learning curve. Over the years they have evolved from novel diagnostic procedures to interventional therapeutic techniques, but along different paths (different scopes or devices and endoscopists specializing exclusively in one or the other technique). However, EUS has gradually developed into a therapeutic technique that requires skills in the use of ERCP devices and stents, leading some ERCP specialists to explore the therapeutic potential of EUS. The corresponding literature, which has grown exponentially, includes recent experiments on combining the two techniques, which have gradually come to be used in routine care in a number of centers, with positive technical, clinical and financial outcomes. We review EUS and ERCP as individual or combined procedures for managing biliopancreatic disorders.

Helicobacter pylori infection does not protect against eosinophilic esophagitis: results from a large multicenter case-control study

OBJECTIVES: Rising trends in eosinophilic esophagitis (EoE) have been repeatedly linked to declining Helicobacter pylori (H. pylori) infection, mostly in retrospective studies. We aimed to prospectively evaluate this inverse association. METHODS: Prospective case‐control study conducted in 23 centers. Children and adults naïve to eradication therapy for H. pylori were included. Cases were EoE patients, whereas controls were defined by esophageal symptoms and <5 eos/HPF on esophageal biopsies. H. pylori status was diagnosed by non‐invasive (excluding serology) or invasive testing off proton pump inhibitor (PPI) therapy for 2 weeks. Atopy was defined by the presence of IgE‐mediated conditions diagnosed by an allergist. RESULTS: 808 individuals, including 404 cases and 404 controls (170 children) were enrolled. Overall H. pylori prevalence was 38% (45% children vs. 37% adults, p 0.009) and was not different between cases and controls (37% vs. 40%, p 0.3; odds ratio (OR) 0.97; 95% confidence interval (CI) 0.73‐1.30), neither in children (42% vs. 46%, p 0.1) nor in adults (36% vs. 38%, p 0.4). Atopy (OR 0.85; 95%CI 0.75‐0.98) and allergic rhinitis (OR 0.81; 95%CI 0.68‐0.98) showed a borderline inverse association with H. pylori infection in EoE patients. This trend was not confirmed for asthma or food allergy. CONCLUSIONS: H. pylori infection was not inversely associated with EoE, neither in children nor in adults. A borderline inverse association was confirmed for atopy and allergic rhinitis, but not asthma of food allergy. Our findings question a true protective role of H. pylori infection against allergic disorders, including EoE.

IL-6, IL-10 and TNFα do not improve early detection of post-endoscopic retrograde cholangiopancreatography acute pancreatitis: a prospective cohort study

The most reliable indicators for post-ERCP acute pancreatitis are elevated amylase levels and abdominal pain 24 hours after ERCP. As ERCP is often performed on an outpatient basis, earlier diagnosis is important. We aimed to identify early predictors of post-ERCP pancreatitis. We prospectively analyzed IL-6, IL-10, TNFα, CRP, amylase and lipase before and 4 hours after ERCP, and studied their association with abdominal pain. We included 510 patients. Post-ERCP pancreatitis occurred in 36 patients (7.1%). IL-6, IL-10, TNFα and CRP were not associated with post-ERCP pancreatitis. Levels of amylase and lipase were higher in patients with pancreatitis (522 U/L and 1808 U/L vs. 78 U/L and 61 U/L, respectively; p < 0.001). A cut-off of 218 U/L for amylase (x2.2 ULN) and 355 U/L for lipase (x6 ULN) had a negative predictive value of 99.2% and 99.5%, respectively. Amylase and lipase present a good correlation (Pearson coefficient 0.912). Among 342 (67.1%) patients without abdominal pain at 4 hours, post-ERCP pancreatitis was diagnosed in 8 (2.3%). Only 4 of these patients presented amylase or lipase > 3 ULN. Amylase and lipase were the only markers of post-ERCP pancreatitis 4 hours after the procedure.

Cholangitis caused by biliary hydatidosis

1 as seen. Just proximal to the major papilla, a large mass f mucin occupied much of the lumen, and papillary ronds were seen emanating from the minor papilla (A). y using gentle force, the colonoscope was advanced irectly through the minor papilla into the dorsal pancretic duct (B). Thick strands of mucin obscured an intrauctal view, but irrigation with 1% N-acetylcysteine leared the visual field and revealed large papillary ronds that carpeted the entire duct (C). Narrow-band maging (Olympus Medical Systems) was activated and ignificantly enhanced visualization of the papillary ronds with clear demarcation of their vascular supply D) (Video 1, available online at www.giejournal.org). o nodules or masses were seen, and random biopsy samles were taken. ERCP performed via the major papilla reealed a rudimentary ventral pancreatic duct without any ommunication with the MPD and a smooth stricture in the

Effect of long-term acid gastric inhibition on bacterial translocation in cirrhotic rats.

BackgroundBacterial translocation (BT) related to intestinal bacterial overgrowth (IBO) plays an important role in the pathogenesis of bacterial infections in cirrhosis. Inhibition of acid gastric secretion promotes IBO and might favor BT. We evaluated the effect of long-term inhibition of acid gastric secretion on BT in cirrhotic rats. MethodsCirrhotic rats with and without ascites induced by oral CCl4 and controls were randomized to treatment with a daily subcutaneous injection of placebo, ranitidine (50 mg/kg), or pantoprazole (8 mg/kg) during 2 weeks. Continuous pH-metry was performed for 2 h before and at the end of treatment; thereafter, a laparotomy to obtain samples of blood, mesenteric lymph nodes, ascites, spleen, liver, and cecal stools was performed. ResultsRanitidine and pantoprazole increased gastric pH as compared with placebo (P<0.001). However, antisecretory drugs increased the incidence of BT only in ascitic rats treated with ranitidine (P<0.05) or pantoprazole (P=0.07) when compared with placebo-treated ascitic rats or cirrhotic rats without ascites treated with the same drug. Cirrhotic ascitic rats treated with pantoprazole showed a trend toward an increased incidence of IBO (P=0.08), a higher ileal malondialdehyde level (P<0.01), and an increased production of tumor necrosis factor-&agr; (P<0.05). ConclusionAlthough inhibition of acid gastric secretion increased gastric pH in all animals, the incidence of BT increased only in ascitic rats, and it was associated with a trend toward an increase in IBO incidence, a higher ileal malondialdehyde level, and an increased production of serum tumor necrosis factor-&agr;. Therefore, antisecretory drugs should be carefully administered to cirrhotic ascitic patients.

Esophageal stent-induced fistulization to an anterior cervical plate

D F c C p Endoscopic management of refractory benign esophageal strictures can be challenging, requiring multiple endoscopic procedures for successful remediation. Retrievable, self-expandable plastic stents (SEPS) have been U.S. Food and Drug Administration approved for this indication. We present an unanticipated complication that occurred after placement and removal of a SEPS, with development of a fistula to an anterior cervical plate, its recognition, management, and resolution.