Device-assisted enteroscopy in the surveillance of intestinal hamartomas in Peutz-Jeghers syndrome.

Background and study aims Peutz-Jeghers syndrome (PJS) is an autosomal-dominant genetic disorder characterized by the formation of hamartomatous polyps in the gastrointestinal tract. These polyps result in significant morbidity due to adverse events (AEs) including intestinal obstruction, bleeding, and malignancy. The aim of this study was to describe the role of device-assisted enteroscopy (DAE) in monitoring and prophylactic polypectomy within the small bowel. Patients and methods Electronic medical records were surveyed to identify all DAE procedures performed in patients with PJS at three US referral centers between January 1, 2007 and January 1, 2020. Individual charts were reviewed to collect and analyze specific data points. Primary end points included AEs associated with DAE-related polypectomy and the rate of laparotomy in PJS patients prior to, and following, index DAE. Secondary data points included patient characteristics, procedural details, and size/location/distribution of small bowel hamartomas. Results Twenty-three patients met our inclusion criteria. Of these, 18 (75%) had previously undergone small bowel surgery prior to index DAE. Between 2007 and 2020, 46 DAEs were performed in these patients with an average of one exam every 2.5 years. A total of 131 polypectomies were performed with an AE rate of 1.5%. None of our cohort required emergent surgery related to AEs of small bowel hamartomas over 336 years of aggregated follow-up. Conclusions Endoscopic management of small bowel polyps in patients with PJS using DAE is an effective strategy for prophylactic removal of hamartomas. DAE surveillance and endoscopic polypectomy is safe and may decrease the need for repeated laparotomy in patients with PJS.

Siderophore-Linked Ruthenium Catalysts for Targeted Allyl Ester Prodrug Activation within Bacterial Cells.

Due to rising resistance, new antibacterial strategies are needed, including methods for targeted antibiotic release. As targeting vectors, chelating molecules called siderophores that are released by bacteria to acquire iron have been investigated for conjugation to antibacterials, leading to the clinically approved drug cefiderocol. The use of small-molecule catalysts for prodrug activation within cells has shown promise in recent years, and here we investigate siderophore-linked ruthenium catalysts for the activation of antibacterial prodrugs within cells. Moxifloxacin-based prodrugs were synthesised, and their catalyst-mediated activation was demonstrated under anaerobic, biologically relevant conditions. In the absence of catalyst, decreased antibacterial activities were observed compared to moxifloxacin versus Escherichia coli K12 (BW25113). A series of siderophore-linked ruthenium catalysts were investigated for prodrug activation, all of which displayed a combinative antibacterial effect with the prodrug, whereas a representative example displayed little toxicity against mammalian cell lines. By employing complementary bacterial growth assays, conjugates containing siderophore units based on catechol and azotochelin were found to be most promising for intracellular prodrug activation.

Clinical Features and Management of Small Bowel Masses Detected During Device-Assisted Enteroscopy: A Multi-Center Experience.

Background: Small bowel mass lesions (SBMLs) are rare, span a range of different histologies and phenotypes, and our understanding of them is limited. Some lesions occur in patients with recognized polyposis syndromes and others arise sporadically. The current literature regarding SBMLs is limited to small retrospective studies, case reports, and small case series. This large multi-center study aims to understand the various clinical presentations, histologies and management options for SBMLs. Methods: After obtaining Institutional Review Board (IRB) approval, electronic records were used to identify all device-assisted enteroscopy (DAE) performed for luminal small bowel evaluation in adult patients at three US referral centers (Duke, LSU and UMass) from January 1, 2014, to October 1, 2020. We identified all patients within this cohort in whom a SBML was detected. Using a focused electronic medical record chart review, we collected patient, procedure, and lesion-related data and used descriptive statistics to explore relationships between these data and outcomes. Results: A total of 218 patients (49 at Duke, 148 at LSU, and 21 at UMass) in this cohort had at least one SBML found on DAE. The most common presenting symptoms were iron-deficiency anemia/bleeding (73.3%) and abnormal imaging (33.6%). Thirty-five percent of patients had symptoms for more than a year prior to their diagnosis. Most patients (71.6%) underwent video capsule endoscopy (VCE) prior to DAE and 84% of these exams showed the lesion. The lesion was seen less frequently (48.9%) on computed tomography (CT) scan performed prior to DAE. The majority of lesions were found on antegrade (56%) or retrograde (29.8%) double-balloon enteroscopy (DBE). The most common lesion phenotypes were submucosal (41.3%) and pedunculated (33%) with a much smaller number being sessile (14.7%) or obstructing/invasive (11%). They were found equally as commonly in the jejunum (46.3%) and ileum (49.5%). Most lesions were 10 - 20 mm in size (47%) but 22.1% were larger than 20 mm. The most common histologies were neuroendocrine tumors (NETs, 20.6%) and hamartomas (20.6%). Primary adenocarcinoma of the small bowel was rare, constituting only 5% of lesions. The majority of polyps (78.4%) were sporadic, compared to 21.7% associated with a polyposis or hereditary cancer syndrome, most commonly Peutz-Jeghers syndrome (18.3%). After DAE, 37.6% were advised to undergo surgical resection and 48% were advised to undergo endoscopic surveillance or no further management because of benign histology or successful endoscopic resection. Conclusions: In this multi-center retrospective study we found that SBMLs are more likely to be sporadic than syndromic, medium in size and either pedunculated or submucosal. NETs and hamartomas predominated and symptoms, most commonly anemia, can be present for more than a year prior to diagnosis. Close to one half of lesions required either no further intervention or only endoscopic surveillance.

Assessment of Video Capsule Endoscopy in the Management of Acute Gastrointestinal Bleeding During the COVID-19 Pandemic.

Importance: Evaluation of acute gastrointestinal (GI) bleeding using invasive endoscopic procedures comprising the standard of care (SOC)-upper endoscopy and colonoscopy-can expose the endoscopy staff to SARS-CoV-2. Video capsule endoscopy (VCE) does not generate aerosols and only requires 1 person to manage the procedure. Objective: To examine the safety of VCE for the initial evaluation of GI bleeding at the peak of the COVID-19 pandemic to identify signs of active bleeding while minimizing patient and personnel exposure, saving personal protective equipment, and avoiding invasive or unnecessary procedures. Design, Setting, and Participants: A multicenter (UMass Memorial Medical Center and Louisiana State University Health Sciences Center) retrospective cohort study including 146 patients with COVID-19 who received VCE as the first-line diagnostic modality was conducted from March 15 to June 15, 2020, compared with SOC in January 2020 for evaluation of GI bleeding. The association between treatment and outcomes was estimated using multivariable regression adjusting for potential confounders. Propensity score matching was used to verify the results. Main Outcomes and Measures: The primary end point was detection of active bleeding or stigmata of recent bleeding. Secondary end points included the number of patients requiring any invasive procedures, number of additional procedures, rates of rebleeding and rehospitalization, transfusion requirements, and mortality. Results: Among 146 patients, 92 (63.0%) were men; mean (SD) age was 64.93 (14.13) years in the COVID-19 group and 61.33 (13.39) years in the SOC group. Active bleeding or stigmata of recent bleeding was observed in 44 (59.5%) patients in the COVID-19 group compared with 18 (25.0%) in the SOC group (adjusted odds ratio, 5.23; 95% CI, 2.23 to 12.27). Only 36 patients (48.7%) in the COVID-19 group required any invasive procedure during the hospitalization compared with 70 (97.2%) in the SOC group (adjusted odds ratio, 0.01; 95% CI, 0.001 to 0.08). The mean (SD) number of invasive procedures was 0.59 (0.77) per patient in the COVID-19 group compared with 1.18 (0.48) per patient in the SOC group (adjusted difference, -0.54; 95% CI, -0.77 to -0.31). Both approaches appeared to be safe and there was no significant difference in transfusion requirements, rebleeding, rehospitalization, or in-hospital mortality. No mortality was attributed to GI bleeding in either group. Conclusions and Relevance: In this cohort study, first-line diagnostic evaluation of acute GI bleeding using VCE appeared to be a safe and useful alternative to the traditional approach of upper endoscopy and colonoscopy. Use of VCE was associated with increased detection of active bleeding and a reduced number of invasive procedures and unnecessary exposure of personnel to SARS-CoV-2 and use of personal protective equipment.

The Role of Provocative Testing and Localization of the Video Capsule Endoscope in the Management of Small Intestinal Bleeding.

The cause of small intestinal bleeding (SIB) may be elusive despite exhaustive testing. This article describes the current understanding of SIB regarding evaluation, with emphasis on the use of video capsule endoscopy (VCE) as a diagnostic procedure. This article addresses the utility of provocative testing in challenging cases and the performance of endoscopic procedures on active antithrombotic therapy. Specific recommendations accompany this article, including use of antithrombotic agents to stimulate bleeding when clearly indicated; performance of endoscopic procedures on active antithrombotic therapy; and progressive adoption of VCE and device-assisted enteroscopy in the inpatient setting.

Use, Yield, and Risk of Device-assisted Enteroscopy in the United States: Results From a Large Retrospective Multicenter Cohort.

INTRODUCTION: Since 2001, device-assisted enteroscopy (DAE) has revolutionized the diagnostic and therapeutic capabilities for managing small bowel pathology. Though commonly performed, there have been no recent large studies to assess the use, yield, and risks of DAE and none that include all 3 DAE modalities. We hypothesized that DAE is safe with high diagnostic and therapeutic yields achieved within reasonable procedure duration and here we present a large retrospective multicenter US study evaluating the use, yield, and complications of DAE. METHODS: After obtaining institutional review board approval, electronic records were used to identify all DAE's performed for luminal small bowel evaluation in adult patients at 4 US referral centers (Duke University Medical Center, New York University Langone Medical Center, Louisiana State University Health Sciences Center, and University of Massachusetts Medical Center) from January 1, 2014 to January 1, 2019. Electronic medical records were reviewed to collect and analyze a variety of procedure-related outcomes. Using the data pooled across centers, descriptive statistics were generated for the patient and procedure-related characteristics and outcomes; relationships between characteristics and outcomes were explored. RESULTS: A total of 1787 DAE's were performed over this 5-year period (392 at Duke University Medical Center, 887 at Louisiana State University Health Sciences Center, 312 at New York University Langone Medical Center, and 195 at University of Massachusetts Medical Center). Of these, there were 1017 (57%) double-balloon, 391 (29%) single-balloon, and 378 (21%) spiral enteroscopies. The mean age of patients undergoing DAE was 66 years and 53% of examinations were performed on women; 18% of patients in the cohort underwent >1 DAE over this time span. A total of 53% of examinations were performed for suspected small bowel bleeding, 31% were directly guided by video capsule endoscopy findings and 8% were performed for abnormal imaging. A total of 85% of examinations used an antegrade approach and DAE took a mean of 45 minutes to complete; 76% of examinations revealed abnormal findings, with vascular, inflammatory, and neoplastic findings seen in 49%, 17%, and 15% of the cohort, respectively. Older age was significantly associated with any abnormal finding, including arteriovenous malformations (P<0.0001); 50% of examinations included a therapeutic maneuver, most commonly argon plasma coagulation/cautery (43%). There were complications in 16 examinations (0.9%) including 2 perforations (0.1%), 6 cases with bleeding (0.3%) and 1 episode of pancreatitis (0.1%). CONCLUSIONS: DAE is most commonly performed to evaluate suspected small bowel bleeding and is commonly directed by video capsule findings. DAE is safe, has a high diagnostic yield, with 76% of examinations showing abnormal findings, and frequently features therapeutic maneuvers. Advancing age is associated with abnormal findings on DAE.

The Pneumococcal Iron Uptake Protein A (PiuA) Specifically Recognizes Tetradentate FeIIIbis- and Mono-Catechol Complexes.

Streptococcus pneumoniae (Spn) is an important Gram-positive human pathogen that causes millions of infections worldwide with an increasing occurrence of antibiotic resistance. Fe acquisition is a crucial virulence determinant in Spn; further, Spn relies on exogenous FeIII-siderophore scavenging to meet nutritional Fe needs. Recent studies suggest that the human catecholamine stress hormone, norepinephrine (NE), facilitates Fe acquisition in Spn under conditions of transferrin-mediated Fe starvation. Here we show that the solute binding lipoprotein PiuA from the piu Fe acquisition ABC transporter PiuBCDA, previously described as an Fe-hemin binding protein, binds tetradentate catechol FeIII complexes, including NE and the hydrolysis products of enterobactin. Two protein-derived ligands (H238, Y300) create a coordinately saturated FeIII complex, which parallel recent studies in the Gram-negative intestinal pathogen Campylobacter jejuni. Our in vitro studies using NMR spectroscopy and 54Fe LC-ICP-MS confirm the FeIII can move from transferrin to apo-PiuA in an NE-dependent manner. Structural analysis of PiuA FeIII-bis-catechol and GaIII-bis-catechol and GaIII-(NE)2 complexes by NMR spectroscopy reveals only localized structural perturbations in PiuA upon ligand binding, largely consistent with recent descriptions of other solute binding proteins of type II ABC transporters. We speculate that tetradentate FeIII complexes formed by mono- and bis-catechol species are important Fe sources in Gram-positive human pathogens, since PiuA functions in the same way as SstD from Staphylococcus aureus.

1H, 13C, 15N backbone resonance assignments of the apo and holo forms of the ABC transporter solute binding protein PiuA from Streptococcus pneumoniae.

Streptococcus pneumoniae is a Gram-positive human pathogen that causes millions of infections worldwide with an increasing occurrence of antibiotic resistance. Iron acquisition is essential for its survival and virulence, especially under host-imposed nutritional immunity. S. pneumoniae expresses several ATP-binding cassette (ABC) transporters to facilitate acquisition under iron limitation, including PitABCD, PiaABCD, and PiuBCDA. The substrate specificity of PiuBCDA is not fully established. Herein, we report the backbone 1H, 13C and 15N resonance assignments of the 31 kDa soluble, extracellular domain of the substrate binding protein PiuA in the apo form and in complex with Ga(III) and the catechol siderophore-mimic 4-LICAM. These studies provide valuable information for further functional studies of interactions with other proteins, metals, and small molecules.

Carbon Nitride as a Ligand: Selective Hydrogenation of Terminal Alkenes Using [(η5 -C5 Me5 )IrCl(g-C3 N4 -κ2 N,N')]Cl.

Anchoring a homogeneous catalyst onto a heterogeneous support facilitates separation of the product from the catalyst, and catalyst-substrate interactions can also modify reactivity. Herein we describe the synthesis of composite materials comprising carbon nitride (g-C3 N4 ) as the heterogeneous support and the well-established homogeneous catalyst moiety [Cp*IrCl]+ (where Cp*=η5 -C5 Me5 ), commonly used for catalytic hydrogenation. Coordination of [Cp*IrCl]+ to g-C3 N4 occurs directly at exposed edge sites with a κ2 N,N' binding motif, leading to a primary inner coordination sphere analogous to known homogeneous complexes of the general class [Cp*IrCl(NN-κ2 N,N')]+ (where N,N'=a bidentate nitrogen ligand). Hydrogenation of unsaturated substrates using the composite catalyst is selective for terminal alkenes, which is attributed to the restricted steric environment of the outer coordination sphere at the edge-sites of g-C3 N4 .

Mimicking salmochelin S1 and the interactions of its Fe(III) complex with periplasmic iron siderophore binding proteins CeuE and VctP.

A mimic of the tetradentate stealth siderophore salmochelin S1, was synthesised, characterised and shown to form Fe(III) complexes with ligand-to-metal ratios of 1:1 and 3:2. Circular dichroism spectroscopy confirmed that the periplasmic binding proteins CeuE and VctP of Campylobacter jejuni and Vibrio cholerae, respectively, bind the Fe(III) complex of the salmochelin mimic by preferentially selecting Λ-configured Fe(III) complexes. Intrinsic fluorescence quenching studies revealed that VctP binds Fe(III) complexes of the mimic and structurally-related catecholate ligands, such as enterobactin, bis(2, 3-dihydroxybenzoyl-l-serine) and bis(2, 3-dihydroxybenzoyl)-1, 5-pentanediamine with higher affinity than does CeuE. Both CeuE and VctP display a clear preference for the tetradentate bis(catecholates) over the tris(catecholate) siderophore enterobactin. These findings are consistent with reports that V. cholerae and C. jejuni utilise the enterobactin hydrolysis product bis(2, 3-dihydroxybenzoyl)-O-seryl serine for the acquisition of Fe(III) and suggest that the role of salmochelin S1 in the iron uptake of enteric pathogens merits further investigation.

Interactions of the periplasmic binding protein CeuE with Fe(III) n-LICAM4- siderophore analogues of varied linker length.

Bacteria use siderophores to mediate the transport of essential Fe(III) into the cell. In Campylobacter jejuni the periplasmic binding protein CeuE, an integral part of the Fe(III) transport system, has adapted to bind tetradentate siderophores using a His and a Tyr side chain to complete the Fe(III) coordination. A series of tetradentate siderophore mimics was synthesized in which the length of the linker between the two iron-binding catecholamide units was increased from four carbon atoms (4-LICAM4-) to five, six and eight (5-, 6-, 8-LICAM4-, respectively). Co-crystal structures with CeuE showed that the inter-planar angles between the iron-binding catecholamide units in the 5-, 6- and 8-LICAM4- structures are very similar (111°, 110° and 110°) and allow for an optimum fit into the binding pocket of CeuE, the inter-planar angle in the structure of 4-LICAM4- is significantly smaller (97°) due to restrictions imposed by the shorter linker. Accordingly, the protein-binding affinity was found to be slightly higher for 5- compared to 4-LICAM4- but decreases for 6- and 8-LICAM4-. The optimum linker length of five matches that present in natural siderophores such as enterobactin and azotochelin. Site-directed mutagenesis was used to investigate the relative importance of the Fe(III)-coordinating residues H227 and Y288.

Pharmacologic provocation combined with endoscopy in refractory cases of GI bleeding.

BACKGROUND AND AIMS: The source of GI bleeding may elude us despite exhaustive testing in some cases. Bleeding in these cases is often related to a vascular lesion that is discernible only when actively bleeding. The objective of this study was to determine the efficacy and safety of endoscopy combined with the administration of antiplatelet and/or anticoagulant agents to stimulate bleeding in order to define a source. METHODS: A retrospective review of a database of device-assisted enteroscopy (DAE) procedures was completed to identify cases in which provocation with antiplatelet or anticoagulant agents was used as part of a GI bleeding evaluation. Procedures were divided into 3 groups based on the method of provocation: patients with a history of bleeding associated with an antiplatelet/anticoagulant (provocation-experienced); patients naïve to these medications (provocation-naïve); and cases of recurrent, overt GI bleeding in which a combination of clopidogrel and intravenous heparin was administered for provocation (Lousiana State University [LSU] protocol). RESULTS: A review of 824 DAE procedures was completed to identify a total of 38 instances in which provocation was attempted in 27 patients. These cases were subdivided into 13 provocation-experienced procedures, 18 provocation-naïve procedures, and 7 LSU protocol procedures. The diagnostic yield of provocative testing per procedure was 53% in the provocation-experienced group, 27% in the provocation-naïve group, and 71% in the full protocol group. Provocative testing was revealing in 15 of 27 patients; angioectasias and Dieulafoy lesions were the most common pathologies. Provocative testing was not beneficial in 4 patients who were eventually diagnosed with bleeding caused by intestinal angioectasias (3) and an aorto-enteric fistula (1). There were no adverse events. CONCLUSIONS: Provocative testing combined with endoscopy can be justified as an option in the diagnostic algorithm of complex cases of GI bleeding when intermittent bleeding related to a vascular lesion, such as an angioectasia or Dieulafoy, is suspected. However, this novel technique should be considered only after standard management has failed to define a bleeding source, and bleeding continues to recur. This is the first reported case series of provocative testing combined with endoscopy.

Device-assisted Enteroscopy for Obscure Gastrointestinal Bleeding in the Setting of Thienopyridine Antiplatelet Therapy.

BACKGROUND: Current guidelines recommend suspending thienopyridine therapy 5 to 7 days before therapeutic endoscopy to reduce the risk of bleeding-related complication. However, interruption of antiplatelet therapy may increase the risk of a cardiovascular event. The aim of this study was to evaluate the safety and diagnostic yield of device-assisted enteroscopy (DAE) with endoscopic therapy in patients receiving thienopyridine antiplatelet therapy. MATERIALS AND METHODS: A retrospective chart review was performed for patients treated in the LSU Health Sciences Gastroenterology Clinics between the dates of October 4, 2007 and February 15, 2015. A total of 774 enteroscopy procedures were reviewed to identify patients on active thienopyridine therapy at the time of DAE. RESULTS: During the study period, a total of 68 patients underwent DAE while on thienopyridine therapy. Confirmed or suspected small bowel bleeding was the most common procedural indication. A total of 143 endoscopic interventions were performed, primarily argon plasma coagulation for ablation of intestinal angioectasias. There were no significant bleeding-related complications associated with these procedures. In addition, the diagnostic yield for these procedures was high (77%) with a significant percentage of patients in the thienopyridine group found to have an active bleeding source at the time of DAE. CONCLUSIONS: The performance of DAE procedures with endoscopic intervention such as argon plasma coagulation may be safe in patients on thienopyridine therapy. Continuing thienopyridines may also increase the diagnostic yield of these procedures by promoting active bleeding from the culprit source.

Bacteria in an intense competition for iron: Key component of the Campylobacter jejuni iron uptake system scavenges enterobactin hydrolysis product.

To acquire essential Fe(III), bacteria produce and secrete siderophores with high affinity and selectivity for Fe(III) to mediate its uptake into the cell. Here, we show that the periplasmic binding protein CeuE of Campylobacter jejuni, which was previously thought to bind the Fe(III) complex of the hexadentate siderophore enterobactin (Kd ∼ 0.4 ± 0.1 µM), preferentially binds the Fe(III) complex of the tetradentate enterobactin hydrolysis product bis(2,3-dihydroxybenzoyl-l-Ser) (H5-bisDHBS) (Kd = 10.1 ± 3.8 nM). The protein selects Λ-configured [Fe(bisDHBS)](2-) from a pool of diastereomeric Fe(III)-bisDHBS species that includes complexes with metal-to-ligand ratios of 1:1 and 2:3. Cocrystal structures show that, in addition to electrostatic interactions and hydrogen bonding, [Fe(bisDHBS)](2-) binds through coordination of His227 and Tyr288 to the iron center. Similar binding is observed for the Fe(III) complex of the bidentate hydrolysis product 2,3-dihydroxybenzoyl-l-Ser, [Fe(monoDHBS)2](3-) The mutation of His227 and Tyr288 to noncoordinating residues (H227L/Y288F) resulted in a substantial loss of affinity for [Fe(bisDHBS)](2-) (Kd ∼ 0.5 ± 0.2 µM). These results suggest a previously unidentified role for CeuE within the Fe(III) uptake system of C. jejuni, provide a molecular-level understanding of the underlying binding pocket adaptations, and rationalize reports on the use of enterobactin hydrolysis products by C. jejuni, Vibrio cholerae, and other bacteria with homologous periplasmic binding proteins.

Variation in small bowel length: factor in achieving total enteroscopy?

BACKGROUND AND AIM: Estimation of small bowel length is of interest following the recent development of device-assisted enteroscopy. This new technology allows access to the deep small bowel, but rates of examination of the entire small bowel (total enteroscopy) differ between study populations. Variation in small bowel length could factor into this observed irregularity in total enteroscopy rates. Medical literature contains limited information regarding small bowel length in living patients and conflicting data regarding small bowel length and its relationship to height and weight. We carried out small bowel measurements on surgical patients to further define the total length of the small bowel and its relationship to height, weight and body mass index (BMI). METHODS: Measurement of ileojejunal length on 91 surgical patients undergoing laparotomy for routine indications. Demographic data were collected for each subject, including height, weight and BMI. RESULTS: Small bowel length was found to vary widely between individuals (average 998.52 cm, range 630-1510 cm). Linear regression analysis demonstrated a statistically significant relationship between small bowel length and height (regression coefficient = 0.0561, P-value = 0.0238). A linear relationship between small bowel length and weight or BMI was not observed. CONCLUSIONS: Length of the small bowel in humans is pertinent to advances in deep enteroscopy and existing surgical applications such as intestinal bypass and prevention of short gut syndrome. If average small bowel length varies with height, total enteroscopy may be easier to achieve in patients who are short in stature.

Interactions of a periplasmic binding protein with a tetradentate siderophore mimic.

Iron-bound structure: The ferric complex of a tetradentate siderophore mimic was synthesized and co-crystallized with the periplasmic binding protein CeuE of Campylobacter jejuni. In addition to electrostatic and hydrogen-bonding interactions between the binding pocket and the substrate, the structure showed direct coordination of two amino acid side chains to the Fe(III) center (orange, see figure).

Distribution of bleeding gastrointestinal angioectasias in a Western population.

AIM: To define which segments of the gastrointestinal tract are most likely to yield angioectasias for ablative therapy. METHODS: A retrospective chart review was performed for patients treated in the Louisiana State University Health Sciences Center Gastroenterology clinics between the dates of July 1, 2007 and October 1, 2010. The selection of cases for review was initiated by use of our electronic medical record to identify all patients with a diagnosis of angioectasia, angiodysplasia, or arteriovenous malformation. Of these cases, chart reviews identified patients who had a complete evaluation of their gastrointestinal tract as defined by at least one upper endoscopy, colonoscopy and small bowel capsule endoscopy within the past three years. Patients without evidence of overt gastrointestinal bleeding or iron deficiency anemia associated with intestinal angioectasias were classified as asymptomatic and excluded from this analysis. Thirty-five patients with confirmed, bleeding intestinal angioectasias who had undergone complete endoscopic evaluation of the gastrointestinal tract were included in the final analysis. RESULTS: A total of 127 cases were reviewed. Sixty-six were excluded during subsequent screening due to lack of complete small bowel evaluation and/or lack of documentation of overt bleeding or iron deficiency anemia. The 61 remaining cases were carefully examined with independent review of endoscopic images as well as complete capsule endoscopy videos. This analysis excluded 26 additional cases due to insufficient records/images for review, incomplete capsule examination, poor capsule visualization or lack of confirmation of typical angioectasias by the principal investigator on independent review. Thirty-five cases met criteria for final analysis. All study patients were age 50 years or older and 13 patients (37.1%) had chronic kidney disease stage 3 or higher. Twenty of 35 patients were taking aspirin (81 mg or 325 mg), clopidogrel, and/or warfarin, with 8/20 on combination therapy. The number and location of angioectasis was documented for each case. Lesions were then classified into the following segments of the gastrointestinal tract: esophagus, stomach, duodenum, jejunum, ileum, right colon and left colon. The location of lesions within the small bowel observed by capsule endoscopy was generally defined by percentage of total small bowel transit time with times of 0%-9%, 10%-39%, and 40%-100% corresponding to the duodenum, jejunum and ileum, respectively. Independent review of complete capsule studies allowed for deviation from this guideline if capsule passage was delayed in one or more segments. In addition, the location and number of angioectasias observed in the small bowel was further modified or confirmed by subsequent device-assisted enteroscopy (DAE) performed in the 83% of cases. In our study population, angioectasias were most commonly found in the jejunum (80%) followed by the duodenum (51%), stomach (22.8%), and right colon (11.4%). Only two patients were found to have angioectasias in the ileum (5.7%). Twenty-one patients (60%) had angioectasias in more than one location. CONCLUSION: Patients being considered for endoscopic ablation of symptomatic angioectasias should undergo push enteroscopy or anterograde DAE and re-inspection of the right colon.

A prospective evaluation of the effect of chronic proton pump inhibitor use on plasma biomarker levels in humans.

OBJECTIVE: Proton pump inhibitors (PPIs) are used primarily to treat gastroesophageal reflux disease. Proton pump inhibitor-induced achlorhydria increases circulating gastrin and chromogranin A (CGA). Chromogranin is a widely used biomarker for the diagnosis and follow-up for gut-based neuroendocrine tumors (NETs). Proton pump inhibitor-induced increases in CGA or gastrin may falsely suggest the presence of a NET when none exists. Pancreastatin, a fragment of CGA, is also commonly used to diagnose and follow NETs. We hypothesized that chronic PPI use would increase circulating plasma gastrin, CGA, and pancreastatin levels. METHODS: Thirty patients who used PPIs for 6 months or more (mean ± SD duration, 3.1 ± 2.5 years) and a separate control group of 30 patients who never used antacid medications were prospectively evaluated with plasma gastrin, CGA, and pancreastatin determinations. RESULTS: Chronic PPI use resulted in significant increases in CGA (15.1 ± 11 vs 131 ± 207 ng/mL; P = 0.005) and significant increases in gastrin (34.8 ± 22.3 vs 167.8 ± 136.2 pg/mL; P = 0.001) compared to controls. In contrast, pancreastatin level in nonusers and chronic PPI users were identical (81.6 ± 36.4 vs 89.4 ± 43.4 pg/mL; P = 0.46). CONCLUSIONS: Pancreastatin levels do not change with chronic PPI use and normal pancreastatin levels may be used to distinguish between drug-induced changes in biomarkers and tumor-related increases in circulating biomarkers.