Kenneth R. McQuaid

Analysis of air contrast barium enema, computed tomographic colonography, and colonoscopy: prospective comparison.

BACKGROUND The usefulness of currently available colon imaging tests, including air contrast barium enema (ACBE), computed tomographic colonography (CTC), and colonoscopy, to detect colon polyps and cancers is uncertain. We aimed to assess the sensitivity of these three imaging tests. METHODS Patients with faecal occult blood, haematochezia, iron-deficiency anaemia, or a family history of colon cancer underwent three separate colon-imaging studies--ACBE, followed 7-14 days later by CTC and colonoscopy on the same day. The primary outcome was detection of colonic polyps and cancers. Outcomes were assessed by building an aggregate view of the colon, taking into account results of all three tests. FINDINGS 614 patients completed all three imaging tests. When analysed on a per-patient basis, for lesions 10 mm or larger in size (n=63), the sensitivity of ACBE was 48% (95% CI 35-61), CTC 59% (46-71, p=0.1083 for CTC vs ACBE), and colonoscopy 98% (91-100, p<0.0001 for colonoscopy vs CTC). For lesions 6-9 mm in size (n=116), sensitivity was 35% for ACBE (27-45), 51% for CTC (41-60, p=0.0080 for CTC vs ACBE), and 99% for colonoscopy (95-100, p<0.0001 for colonoscopy vs CTC). For lesions of 10 mm or larger in size, the specificity was greater for colonoscopy (0.996) than for either ACBE (0.90) or CTC (0.96) and declined for ACBE and CTC when smaller lesions were considered. INTERPRETATION Colonoscopy was more sensitive than other tests, as currently undertaken, for detection of colonic polyps and cancers. These data have important implications for diagnostic use of colon imaging tests.

A systematic review and meta-analysis of randomized, controlled trials of moderate sedation for routine endoscopic procedures.

BACKGROUND Numerous agents are available for moderate sedation in endoscopy. OBJECTIVE Our purpose was to compare efficacy, safety, and efficiency of agents used for moderate sedation in EGD or colonoscopy. DESIGN Systematic review of computerized bibliographic databases for randomized trials of moderate sedation that compared 2 active regimens or 1 active regimen with placebo or no sedation. PATIENTS Unselected adults undergoing EGD or colonoscopy with a goal of moderate sedation. MAIN OUTCOME MEASUREMENTS Sedation-related complications, patient assessments (satisfaction, pain, memory, willingness to repeat examination), physician assessments (satisfaction, level of sedation, patient cooperation, examination quality), and procedure-related efficiency outcomes (sedation, procedure, or recovery time). RESULTS Thirty-six studies (N = 3918 patients) were included. Sedation improved patient satisfaction (relative risk [RR] = 2.29, range 1.16-4.53) and willingness to repeat EGD (RR = 1.25, range 1.13-1.38) versus no sedation. Midazolam provided superior patient satisfaction to diazepam (RR = 1.18, range 1.07-1.29) and less frequent memory of EGD (RR = 0.57, range 0.50-0.60) versus diazepam. Adverse events and patient/physician assessments were not significantly different for midazolam (with or without narcotics) versus propofol except for slightly less patient satisfaction (RR = 0.90, range 0.83-0.97) and more frequent memory (RR = 3.00, range 1.25-7.21) with midazolam plus narcotics. Procedure times were similar, but sedation and recovery times were shorter with propofol than midazolam-based regimens. LIMITATIONS Marked variability in design, regimens tested, and outcomes assessed; relatively poor methodologic quality (Jadad score </=3 in 23/36 trials). CONCLUSIONS Moderate sedation provides a high level of physician and patient satisfaction and a low risk of serious adverse events with all currently available agents. Midazolam-based regimens have longer sedation and recovery times than does propofol.

Endoscopic Therapy for Bleeding Ulcers: An Evidence-Based Approach Based on Meta-Analyses of Randomized Controlled Trials

The aim of this study was to determine appropriate endoscopic treatment of patients with bleeding ulcers by synthesizing results of randomized controlled trials. We performed dual independent bibliographic database searches to identify randomized trials of thermal therapy, injection therapy, or clips for bleeding ulcers with active bleeding, visible vessels, or clots, focusing on results from studies without second-look endoscopy and re-treatment. The primary end point was further (persistent plus recurrent) bleeding. Compared with epinephrine, further bleeding was reduced significantly by other monotherapies (relative risk [RR], 0.58 [95% CI, 0.36-0.93]; number-needed-to-treat [NNT], 9 [95% CI, 5-53]), and epinephrine followed by another modality (RR, 0.34 [95% CI, 0.23-0.50]; NNT, 5 [95% CI, 5-7]); epinephrine was not significantly less effective in studies with second-look and re-treatment. Compared with no endoscopic therapy, further bleeding was reduced by thermal contact (heater probe, bipolar electrocoagulation) (RR, 0.44 [95% CI, 0.36-0.54]; NNT, 4 [95% CI, 3-5]) and sclerosant therapy (RR, 0.56 [95% CI, 0.38-0.83]; NNT, 5 [95% CI, 4-13]). Clips were more effective than epinephrine (RR, 0.22 [95% CI, 0.09-0.55]; NNT, 5 [95% CI, 4-9]), but not different than other therapies, although the latter studies were heterogeneous, showing better and worse results for clips. Endoscopic therapy was effective for active bleeding (RR, 0.29 [95% CI, 0.20-0.43]; NNT, 2 [95% CI, 2-2]) and a nonbleeding visible vessel (RR, 0.49; [95% CI, 0.40-0.59]; NNT, 5 [95% CI, 4-6]), but not for a clot. Bolus followed by continuous-infusion proton pump inhibitor after endoscopic therapy significantly improved outcome compared with placebo/no therapy (RR, 0.40 [95% CI, 0.28-0.59]; NNT, 12 [95% CI, 10-18]), but not compared with histamine(2)-receptor antagonists. Thermal devices, sclerosants, clips, and thrombin/fibrin glue appear to be effective endoscopic hemostatic therapies. Epinephrine should not be used alone. Endoscopic therapy should be performed for ulcers with active bleeding and nonbleeding visible vessels, but efficacy is uncertain for clots. Bolus followed by continuous-infusion intravenous proton pump inhibitor should be used after endoscopic therapy.

Effect of raltegravir-containing intensification on HIV burden and T-cell activation in multiple gut sites of HIV-positive adults on suppressive antiretroviral therapy

Objective:To determine whether raltegravir-containing antiretroviral therapy (ART) intensification reduces HIV levels in the gut. Design:Open-label study in HIV-positive adults on ART with plasma HIV RNA below 40 copies/ml. Methods:Seven HIV-positive adults received 12 weeks of ART intensification with raltegravir alone or in combination with efavirenz or darunavir. Gut cells were obtained by upper and lower endoscopy with biopsies from duodenum, ileum, colon, and rectum at baseline and 12 weeks. Study outcomes included plasma HIV RNA, HIV DNA and RNA from peripheral blood mononuclear cells (PBMC) and four gut sites, T-cell subsets, and activation markers. Results:Intensification produced no consistent decrease in HIV RNA in the plasma, PBMC, duodenum, colon, or rectum. However, five of seven participants had a decrease in unspliced HIV RNA per 106 CD4+ T cells in the ileum. There was a trend towards decreased T-cell activation in all sites, which was greatest for CD8+ T cells in the ileum and PBMC, and a trend towards increased CD4+ T cells in the ileum. Conclusion:Most HIV RNA and DNA in the blood and gut is not the result of ongoing replication that can be impacted by short-term intensification with raltegravir. However, the ileum may support ongoing productive infection in some patients on ART, even if the contribution to plasma RNA is not discernible.

Differences in HIV Burden and Immune Activation within the Gut of HIV-Positive Patients Receiving Suppressive Antiretroviral Therapy

BACKGROUND The gut is a major reservoir for human immunodeficiency virus (HIV) in patients receiving antiretroviral therapy (ART). We hypothesized that distinct immune environments within the gut may support varying levels of HIV. METHODS In 8 HIV-1-positive adults who were receiving ART and had CD4(+) T cell counts of >200 cells/μL and plasma viral loads of <40 copies/mL, levels of HIV and T cell activation were measured in blood samples and endoscopic biopsy specimens from the duodenum, ileum, ascending colon, and rectum. RESULTS HIV DNA and RNA levels per CD4(+) T cell were higher in all 4 gut sites compared with those in the blood. HIV DNA levels increased from the duodenum to the rectum, whereas the median HIV RNA level peaked in the ileum. HIV DNA levels correlated positively with T cell activation markers in peripheral blood mononuclear cells (PBMCs) but negatively with T cell activation markers in the gut. Multiply spliced RNA was infrequently detected in gut, and ratios of unspliced RNA to DNA were lower in the colon and rectum than in PBMCs, which reflects paradoxically low HIV transcription, given the higher level of T cell activation in the gut. CONCLUSIONS HIV DNA and RNA are both concentrated in the gut, but the inverse relationship between HIV DNA levels and T cell activation in the gut and the paradoxically low levels of HIV expression in the large bowel suggest that different processes drive HIV persistence in the blood and gut. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT00884793 (PLUS1).

Endoscopic Sclerotherapy Compared with Percutaneous Transjugular Intrahepatic Portosystemic Shunt after Initial Sclerotherapy in Patients with Acute Variceal Hemorrhage: A Randomized, Controlled Trial

During the past 15 years, endoscopic sclerotherapy and, more recently, band ligation and such pharmacologic agents as octreotide have eclipsed surgical shunting as the preferred method for controlling acute variceal hemorrhage. The status of sclerotherapy for the long-term management of patients with bleeding varices, however, remains controversial. In a previous controlled clinical trial comparing endoscopic sclerotherapy with surgical portacaval shunting [1], we enrolled 64 adult patients with Child class C cirrhosis and active hemorrhage from esophageal varices. At the index hospitalization, patients randomly assigned to sclerotherapy required less blood transfusion and fewer days of hospitalization than did those randomly assigned to shunt surgery. During the initial follow-up period, which extended for a mean of 530 days after randomization, 75% of the patients treated with sclerotherapy were hospitalized for recurrent variceal hemorrhage but none of the patients who had had shunt surgery were rehospitalized [1]. Although patients treated with sclerotherapy had longer hospital stays and received more blood transfusions during short-term follow-up, a longer follow-up study [2] showed no difference in survival or overall health care costs between patients treated with sclerotherapy and those treated with surgical shunt. The transjugular intrahepatic portosystemic shunt (TIPS) procedure is a nonsurgical procedure in which an expandable metal prosthesis is used to connect an intrahepatic portal vein with an adjacent hepatic vein [3, 4]. In our initial report on 100 patients having this procedure [3], TIPS stent placement was technically successful in 96 patients and variceal hemorrhage was controlled in 88 of 94 patients [3]. Furthermore, the 30-day mortality rate was only 13% in patients treated with TIPS. These data, as well as those of other researchers who used radiographically placed portosystemic stents, suggest that TIPS might be more cost-effective than sclerotherapy; however, data comparing the two procedures are limited [5-10]. Therefore, we did a randomized, controlled trial in patients with massive acute variceal hemorrhage in an effort to compare the two therapies for the prevention of recurrent variceal hemorrhage. Methods From November 1991 through December 1995, we enrolled 49 adults who had cirrhosis and endoscopically documented bleeding from esophageal varices. We excluded an estimated additional 250 patients with bleeding varices whom we had seen during the study period (vide infra). Our study protocol was approved by the Committee on Human Research of the University of California, San Francisco. Patients who were admitted to San Francisco General Hospital, University of California Medical Center, and Veterans Affairs Medical Center (all located in San Francisco, California) with massive or submassive acute gastrointestinal tract hemorrhage from large esophageal varices were approached for consent and randomization within 24 hours of admission. Massive hemorrhage was defined as bleeding associated with shock (systolic blood pressure < 80 mm Hg). Submassive hemorrhage was defined as hemorrhage associated with postural vital sign changes (upright pulse rate increased by 20 beats per minute compared with supine pulse rate; upright systolic blood pressure decreased by 20 mm Hg compared with supine blood pressure). The 250 excluded patients were excluded for the following reasons: They were prisoners; they were younger than 18 or older than 75 years of age; they had had a cerebrovascular accident within 3 months before the onset of bleeding; they refused to accept blood products; or they had gastric variceal hemorrhage, electrocardiographic changes compatible with acute myocardial infarction, a Po 2 less than 70 mm Hg or an arterial pH of 7.20 or less on room air at the time of evaluation for eligibility, a serum creatinine level of 221 mol/L or more, a prothrombin time at least 5 seconds longer than control (despite the use of fresh frozen plasma), a platelet count less than 50 109/L, stage IV hepatic encephalopathy, cancer other than skin cancer, the acquired immunodeficiency syndrome (AIDS) or advanced AIDS-related complex, sepsis, pneumonia, peritonitis, clinical evidence of alcoholic hepatitis, a serum bilirubin concentration of 7 mg/dL or more, thrombosis of the portal vein, thrombosis of the hepatic veins, or thrombosis of the inferior vena cava as determined by Doppler ultrasonography. All patients received endoscopic sclerotherapy at the time of the initial endoscopic procedure that established the source of hemorrhage as esophageal varices. Patients were deemed eligible for participation if they presented with hemodynamically submassive or massive hemorrhage and were found to have large (>1 cm across) distal esophageal varices with cherry red spots, hematocystic spots, or red wale signs. Before randomization, all patients had patency of the portal venous system (main, right, and left portal veins and the splenic vein) and hepatic veins determined by real-time color and pulse-wave Doppler ultrasonography. After we obtained informed consent, we used serially numbered, sealed, opaque envelopes to randomly assign patients either to repeated sclerotherapy or to TIPS. If neither the patient nor the patients next of kin was able to give informed consent, a patient advocate was designated to consider the invitation to participate. Patients randomly assigned to sclerotherapy received treatment every 2 to 7 days during the initial hospitalization; treatment consisted of 0.5- to 2.0-mL injections of ethanolamine oleate solution per varix. Repeated endoscopy and sclerotherapy treatments were done weekly after discharge from the initial hospitalization. As much as 30 mL of ethanolamine oleate solution was used per treatment session. All visible varices were injected within the distal 7 to 10 cm of the esophagus. In patients who developed sclerotherapy-associated ulcers, repeated endoscopy was scheduled to be done 2 to 7 days after the notation of ulcers to assess interval healing. Patients assigned to the TIPS group had the procedure within 48 hours of randomization; the procedure was performed by one of six radiologists skilled in this procedure, as described elsewhere [3]. Catheterization of the hepatic vein was done through the right internal jugular vein. A tract between a suitable hepatic vein and a suitable portal vein was established by needle set (Ring TIPS set, Cook, Inc., Bloomington, Indiana), dilated with a balloon over a guidewire, and then maintained by one or more expandable metal mesh stents (Wallstent, Schneider, Inc., Minneapolis, Minnesota). The adequacy of the portosystemic shunt was documented by contrast injection and manometric measurement at the time of the initial procedure. A target portal vein-to-hepatic vein pressure gradient of 12 mm Hg or less was achieved in all cases. Persistent varices opacified at portal venography after adequate stenting were occluded by using embolization coils. Preprocedural data recorded prospectively included sex, age, vital signs at admission, physical examination findings at admission (including presence of encephalopathy and ascites), nutritional status, results of laboratory tests, and Child-Pugh score [11]. Prospectively identified outcome variables after randomization included death, rebleeding, liver transplantation, total transfusion requirements, onset and presence of encephalopathy, cost of managing variceal hemorrhage after randomization, total duration of hospitalization for variceal hemorrhage and any related encephalopathy, and complications of therapy. Nutritional status was defined as malnourished if the patient had gross muscle wasting, had cachexia, or had lost at least 10% of body weight during the previous 6 months. Bleeding after randomization was defined as bloody or coffee grounds emesis (hemetemesis, melenemesis) or liquid black stools (melena) with a decrease in hematocrit sufficient to warrant transfusion. Hepatic encephalopathy was defined clinically by the presence of asterixis, gross disorientation or agitation, or frank somnolence or coma in the absence of another identifiable cause. Presence of ascites was determined by both ultrasonography and clinical assessment (shifting dullness, fluid wave, gross distention) for all patients initially and for patients in the TIPS group having follow-up Doppler ultrasonography. For patients assigned to sclerotherapy, presence of ascites was subsequently determined by clinical criteria alone. Follow-up information was obtained through face-to-face interviews, telephone interviews, or chart reviews and was obtained from the patient, family, physician, or all three sources. The total cost of health care per patient was calculated as the sum of all real costs for inpatient and outpatient hospital care, including hospital expenditures and costs for professional services from the day of randomization until death or the last follow-up visit. In addition, all outpatient costs for endoscopic sclerotherapy, Doppler ultrasonography, and stent revision during the follow-up period were included. We used the actual cost to the hospital or medical staff, or both, of providing a service or procedure (rather than billing charges or collections). For example, the cost of an endoscopic sclerotherapy session was determined by summating the following: 1 hour of a gastroenterologists time plus benefits (derived from personnel pay records); 2 hours of a registered nurses time plus benefits; the invoice cost of disposable sclerotherapy catheters, bite blocks, and intravenous tubing; the pharmacy costs of all drugs, including the sclerosant agent; the estimated depreciation of an Olympus GIT-IT100 videoendoscope (Lake Success, New York); endoscopic processing costs; 1 hour of recovery room personnel time; and costs of recovery supplies. Outcome variables were compared, using the intention-to-tre

SCENIC International Consensus Statement on Surveillance and Management of Dysplasia in Inflammatory Bowel Disease

Patients with ulcerative colitis or Crohn’s colitis have an increased risk of colorectal cancer (CRC). Most cases are believed to arise from dysplasia, and surveillance colonoscopy therefore is recommended to detect dysplasia. Detection of dysplasia traditionally has relied on both examination of the mucosa with targeted biopsies of visible lesions and extensive random biopsies to identify invisible dysplasia. Current U.S. guidelines recommend obtaining at least 32 random biopsy specimens from all segments of the colon as the foundation of endoscopic surveillance. However, much of the evidence that provides a basis for these recommendations is from older literature, when most dysplasia was diagnosed on random biopsies of colon mucosa. With the advent of video endoscopy and newer endoscopic technologies, investigators now report that most dysplasia discovered in patients with inflammatory bowel disease (IBD) is visible. Such a paradigm shift may have important implications for the surveillance and management of dysplasia. The evolving evidence regarding newer endoscopic methods to detect dysplasia has resulted in variation among guideline recommendations from organizations around the world. We therefore sought to develop unifying consensus recommendations addressing 2 issues: (1) How should surveillance colonoscopy for detection of dysplasia be performed? (2) How should dysplasia identified at colonoscopy be managed?

Relative Frequency of Upper Gastrointestinal and Colonic Lesions in Patients with Positive Fecal Occult-Blood Tests

Background Although bleeding lesions anywhere in the gastrointestinal tract can cause a positive reaction on guaiac-based fecal occult-blood tests, the relative frequency of upper gastrointestinal and colonic lesions is unknown. Methods During a period of 30 months, we prospectively studied all patients with at least one stool specimen containing fecal occult blood who were referred for further evaluation. Fecal occult blood was detected by standard guaiac-based tests of stool specimens obtained as part of routine screening or of stool obtained by digital rectal examination. Patients with documented iron-deficiency anemia or active gastrointestinal bleeding were excluded from the study. All participants had a detailed history taken and underwent colonoscopy, followed by esophagogastroduodenoscopy. Results Of the 409 patients with fecal occult blood who were referred, 310 were potentially eligible to participate, and 248 (mean age, 61 years; range, 40 to 89) were studied; 40 percent were women. We identifi...

SCENIC international consensus statement on surveillance and management of dysplasia in inflammatory bowel disease.

Section of Digestive Diseases, Yale School of Medicine, New Haven, Connecticut; Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut; Veterans Affairs Palo Alto Healthcare System and Stanford University School of Medicine (affiliate), Palo Alto, California; Division of Gastroenterology, McGill University, Montreal, Quebec, Canada; University of California at San Francisco, Veterans Affairs Medical Center, San Francisco, California; University of Leeds, Leeds, United Kingdom

Upper Gastrointestinal Symptoms in North America

The aim of this study was to determine the prevalence of upper gastrointestinal symptoms (UGIS) in a general population and quantify the relationship of those symptoms to health-care utilization and quality of life. In-person interviews were conducted with 2056 United States and Canadian residents selected at random. Subjects reported frequency and severity for 11 symptoms, prescription and over-the-counter medication use, primary care and specialty physician visits in prior three months, and completed the Psychological General Well-Being Scale. For analyses, subjects were classified into four mutually exclusive symptom groups: gastroesophageal reflux disease (GERD) -like, GERD plus motility-like (GERD+), ulcerlike, and motility-like. Of the total sample, 51.4% reported the occurrence of at least one UGIS in the prior three months. Subjects in the GERD+ and ulcer groups used more prescription medications and were more likely to see a physician about the symptoms (P < 0.001). Subjects with symptoms demonstrated poorer quality of life compared to subjects with no symptoms. The prevalence of UGIS in the general population is high and symptoms are associated with significant health-care utilization and poorer quality of life.