Dennis M. Jensen

Urgent colonoscopy for the diagnosis and treatment of severe diverticular hemorrhage

BACKGROUND Although endoscopy is often used to diagnose and treat acute upper gastrointestinal bleeding, its role in the management of diverticulosis and lower gastrointestinal bleeding is uncertain. METHODS We studied the role of urgent colonoscopy in the diagnosis and treatment of 121 patients with severe hematochezia and diverticulosis. All patients were hospitalized, received blood transfusions as needed, and received a purge to rid the colon of clots, stool, and blood. Colonoscopy was performed within 6 to 12 hours after hospitalization or the diagnosis of hematochezia. Among the first 73 patients, those with continued diverticular bleeding underwent hemicolectomy. For the subsequent 48 patients, those requiring treatment received therapy, such as epinephrine injections or bipolar coagulation, through the colonoscope. RESULTS Of the first 73 patients, 17 (23 percent) had definite signs of diverticular hemorrhage (active bleeding in 6, nonbleeding visible vessels in 4, and adherent clots in 7). Nine of the 17 had additional bleeding after colonoscopy, and 6 of these required hemicolectomy. Of the subsequent 48 patients, 10 (21 percent) had definite signs of diverticular hemorrhage (active bleeding in 5, nonbleeding visible vessels in 2, and adherent clots in 3). An additional 14 patients in this group (29 percent) were presumed to have diverticular bleeding because although they had no stigmata of diverticular hemorrhage, no other source of bleeding was identified. The other 24 patients (50 percent) had other identified sources of bleeding. All 10 patients with definite diverticular hemorrhage were treated endoscopically; none had recurrent bleeding or required surgery. CONCLUSIONS Among patients with severe hematochezia and diverticulosis, at least one fifth have definite diverticular hemorrhage. Colonoscopic treatment of such patients with epinephrine injections, bipolar coagulation, or both may prevent recurrent bleeding and decrease the need for surgery.

Diagnosis and treatment of severe hematochezia. The role of urgent colonoscopy after purge.

The purpose of this study was to prospectively evaluate (a) the diagnosis and treatment of 80 consecutive patients with severe, ongoing hematochezia from unknown source and (b) the effectiveness and safety of urgent colonoscopy after oral purge. Fifty-two men and 28 women (mean age, 64.5 yr) received a mean of 6.5 U of blood and had negative anoscopy, rigid sigmoidoscopy, and nasogastric tube aspiration before our evaluation. Because of ongoing severe hematochezia in the intensive care unit, urgent diagnosis and treatment was recommended by the attending physicians and surgeons. Emergency panendoscopy was performed before purge. Urgent colonoscopy was performed in the intensive care unit after patients received oral purge and their gut was cleared of blood, clots, and stool. The final diagnosis in these patients was 74% colonic lesions (30% angiomata, 17% diverticulosis, 11% polyps or cancer, 9% focal ulcers, 7% other), 11% upper gastrointestinal lesions, and 9% presumed small bowel lesions. No lesion site was identified in 6%. Clinically significant fluid retention (medically controlled) occurred in 4% of patients after purge. Sixty-four percent of patients had intervention for control of bleeding: 39% had therapeutic endoscopy, 24% surgery, and 1% therapeutic angiography. For 22 patients who also had emergency visceral angiography, the diagnostic yield was 14% and the complication rate was 9%. Our conclusions for patients with severe ongoing hematochezia from an unknown site were as follows. (a) Oral purge was effective and safe for cleansing the colon of stool, clots, and blood. Sulfate purge appeared to be safer than saline purge. (b) Before urgent colonoscopy and purge, emergency panendoscopy was indicated to exclude an upper gastrointestinal bleeding source. (c) Urgent colonoscopy after purge was effective, safe, and often diagnostic. (d) Compared with urgent colonoscopy, urgent visceral angiography was often nondiagnostic. However, the examinations may be complementary. (e) Hemostasis via colonoscopy has a definitive role in the treatment of some focal colonic lesions such as bleeding angiomata.

Management of patients with ulcer bleeding.

This guideline presents recommendations for the step-wise management of patients with overt upper gastrointestinal bleeding. Hemodynamic status is first assessed, and resuscitation initiated as needed. Patients are risk-stratified based on features such as hemodynamic status, comorbidities, age, and laboratory tests. Pre-endoscopic erythromycin is considered to increase diagnostic yield at first endoscopy. Pre-endoscopic proton pump inhibitor (PPI) may be considered to decrease the need for endoscopic therapy but does not improve clinical outcomes. Upper endoscopy is generally performed within 24h. The endoscopic features of ulcers direct further management. Patients with active bleeding or non-bleeding visible vessels receive endoscopic therapy (e.g., bipolar electrocoagulation, heater probe, sclerosant, clips) and those with an adherent clot may receive endoscopic therapy; these patients then receive intravenous PPI with a bolus followed by continuous infusion. Patients with flat spots or clean-based ulcers do not require endoscopic therapy or intensive PPI therapy. Recurrent bleeding after endoscopic therapy is treated with a second endoscopic treatment; if bleeding persists or recurs, treatment with surgery or interventional radiology is undertaken. Prevention of recurrent bleeding is based on the etiology of the bleeding ulcer. H. pylori is eradicated and after cure is documented anti-ulcer therapy is generally not given. Nonsteroidal anti-inflammatory drugs (NSAIDs) are stopped; if they must be resumed low-dose COX-2-selective NSAID plus PPI is used. Patients with established cardiovascular disease who require aspirin should start PPI and generally re-institute aspirin soon after bleeding ceases (within 7 days and ideally 1–3 days). Patients with idiopathic ulcers receive long-term anti-ulcer therapy.

Intravenous Esomeprazole for Prevention of Recurrent Peptic Ulcer Bleeding: A Randomized Trial

BACKGROUND Use of proton-pump inhibitors in the management of peptic ulcer bleeding is controversial because discrepant results have been reported in different ethnic groups. OBJECTIVE To determine whether intravenous esomeprazole prevents recurrent peptic ulcer bleeding better than placebo in a multiethnic patient sample. DESIGN Randomized trial conducted between October 2005 and December 2007; patients, providers, and researchers were blinded to group assignment. SETTING 91 hospital emergency departments in 16 countries. PATIENTS Patients 18 years or older with peptic ulcer bleeding from a single gastric or duodenal ulcer showing high-risk stigmata. INTERVENTION Intravenous esomeprazole bolus, 80 mg, followed by 8-mg/h infusion, over 72 hours or matching placebo, each given after successful endoscopic hemostasis. Intervention was allocated by computer-generated randomization. After infusion, both groups received oral esomeprazole, 40 mg/d, for 27 days. MEASUREMENTS The primary end point was rate of clinically significant recurrent bleeding within 72 hours. Recurrent bleeding within 7 and 30 days, death, surgery, endoscopic re-treatment, blood transfusions, hospitalization, and safety were also assessed. RESULTS Of 767 patients randomly assigned, 764 provided data for an intention-to-treat analysis (375 esomeprazole recipients and 389 placebo recipients). Fewer patients receiving intravenous esomeprazole (22 of 375) had recurrent bleeding within 72 hours than those receiving placebo (40 of 389) (5.9% vs. 10.3%; difference, 4.4 percentage points [95% CI, 0.6% to 8.3%]; P = 0.026). The difference in bleeding recurrence remained significant at 7 days and 30 days (P = 0.010). Esomeprazole also reduced endoscopic re-treatment (6.4% vs. 11.6%; difference, 5.2 percentage points [95% CI of difference, 1.1 percentage points to 9.2 percentage points]; P = 0.012), surgery (2.7% vs. 5.4%), and all-cause mortality rates (0.8% vs. 2.1%) more than placebo, although differences for the latter 2 comparisons were not significant. About 10% and 40% of patients in both groups reported serious and nonserious adverse events, respectively. LIMITATION Endoscopic therapy was not completely standardized; some patients received epinephrine injection, thermal coagulation, or hemoclips alone, whereas others received combination therapy, but there were similar proportions with single therapy in each group. CONCLUSION High-dose intravenous esomeprazole given after successful endoscopic therapy to patients with high-risk peptic ulcer bleeding reduced recurrent bleeding at 72 hours and had sustained clinical benefits for up to 30 days. PRIMARY FUNDING SOURCE AstraZeneca Research and Development.

Development and evaluation of the liver disease quality of life instrument in persons with advanced, chronic liver disease - The LDQOL 1.0

Development and evaluation of the liver disease quality of life instrument in persons with advanced, chronic liver disease—the LDQOL 1.0

Experimental comparison of endoscopic yttrium-aluminum-garnet laser, electrosurgery, and heater probe for canine gut arterial coagulation. Importance of compression and avoidance of erosion.

We compared five endoscopic thermal devices that have been used clinically for control of arterial bleeding in the gastrointestinal tract: neodymium:yttrium-aluminum-garnet (YAG) laser, electrofulguration, monopolar and bipolar electrocoagulation, and heater probe. In canine models we determined the ability to coagulate arteries of varying size and depth. The most effective method for coagulation of medium size arteries was first to occlude the vessel by compression, then to apply heat to seal it (coaptive coagulation). For the contact probes (monopolar, bipolar, and heater probes), the depth of tissue coagulation was controlled by varying probe appositional force and energy, and coagulation of deep arteries was possible. Undesirable erosion of tissue and vessels was noted with electrical sparking from the monopolar electrode and with YAG laser at high power density. In contrast, heater probe and bipolar electrocoagulation did not produce tissue erosion at any instrument setting. In this comparative study of arterial coagulation, overall ranking was as follows: heater probe = bipolar electrocoagulation greater than monopolar electrocoagulation greater than neodymium:YAG laser greater than electrofulguration greater than control. In our opinion these data should assist the clinician or investigator who plans to coagulate arterial bleeding lesions such as peptic ulcers, although further clinical research will be needed to verify these experimental results.

Randomized trial of argon plasma coagulation vs. multipolar electrocoagulation for ablation of Barrett's esophagus

BACKGROUND Endoscopic ablation of Barretts esophagus has been described in which various thermocoagulation modalities are used in combination with a high dose of a proton pump inhibitor. No randomized comparison of ablation strategies has been published. METHODS Referred patients were screened to identify those with Barretts esophagus 2 to 7 cm in length, without high-grade dysplasia or cancer. Included patients received pantoprazole (40 mg twice a day), followed by randomization to treatment with argon plasma coagulation (APC) or multipolar electrocoagulation (MPEC). The primary outcome measure was the number of treatment sessions required for endoscopic ablation. RESULTS Of 235 patients screened, 52 were randomized. The mean length of Barretts esophagus was 3.1 cm in the MPEC group vs. 4.0 cm in the APC group (p = 0.03). Otherwise, the treatment groups were similar with regard to baseline characteristics. The mean number of treatment sessions required for endoscopic ablation was 2.9 for MPEC vs. 3.8 for APC (p = 0.04) in an intention-to-treat analysis (p = 0.249, after adjustment for the difference in length of Barretts esophagus). The proportion of patients in which ablation was endoscopically achieved proximal to the gastroesophageal junction was 88% for the MPEC group vs. 81% for the APC group (p = 0.68) and histologically achieved in 81% for MPEC vs. 65% for APC (p = 0.21). The mean time required for the first treatment session was 6 minutes with MPEC vs. 10 minutes with APC (p = 0.01) in per protocol analysis. There was no serious adverse event, but transient moderate to severe upper-GI symptoms occurred after MPEC in 8% vs. 13% after APC (p = 0.64). Conclusions Although there were no statistically significant differences, ablation of Barretts esophagus with pantoprazole and MPEC required numerically fewer treatment sessions, and endoscopic and histologic ablation was achieved in a greater proportion of patients compared with treatment with pantoprazole and APC.

A Controlled Study of Ranitidine for the Prevention of Recurrent Hemorrhage from Duodenal Ulcer

BACKGROUND Hemorrhage is the most common complication of duodenal ulcer disease, but there is little information about the effectiveness and safety of long-term maintenance therapy with histamine H2-receptor blockers. METHODS We conducted a double-blind study in patients with endoscopically documented hemorrhage from duodenal ulcers. Patients were randomly assigned to maintenance therapy with ranitidine (150 mg at night) or placebo and were followed for up to three years. Endoscopy was performed at base line (to document that the ulcers had healed), at exit from the study, and when a patient had persistent ulcer symptoms unrelieved by antacids or had gastrointestinal bleeding. Symptomatic relapses without bleeding were treated with ranitidine; if the ulcer healed within eight weeks, the patient resumed taking the assigned study medication. RESULTS The two groups were similar at entry, which usually occurred about three months after the index hemorrhage. After a mean follow-up of 61 weeks, 3 of the 32 patients treated with ranitidine had recurrent hemorrhage, as compared with 12 of the 33 given placebo (P < 0.05). Half the episodes of recurrent bleeding were asymptomatic. One patient in the ranitidine group withdrew from the study because of asymptomatic thrombocytopenia during the first month. CONCLUSIONS For patients whose duodenal ulcers heal after severe hemorrhage, long-term maintenance therapy with ranitidine is safe and reduces the risk of recurrent bleeding.

Lower Gastrointestinal Events in a Double-Blind Trial of the Cyclo-Oxygenase-2 Selective Inhibitor Etoricoxib and the Traditional Nonsteroidal Anti-Inflammatory Drug Diclofenac

BACKGROUND & AIMS Nonsteroidal anti-inflammatory drugs (NSAIDs) cause lower gastrointestinal (GI) clinical events such as bleeding. Cyclo-oxygenase (COX)-2 selective inhibitors decrease upper GI events, but no prospective trial has prespecified assessment of lower GI clinical events. METHODS Patients >or=50 years old with osteoarthritis or rheumatoid arthritis were randomly assigned to etoricoxib (60 or 90 mg qd) or diclofenac (150 mg qd). Lower GI clinical events, confirmed by a blinded adjudication committee, included perforation or obstruction requiring hospitalization or bleeding (gross or occult rectal bleeding without upper GI cause associated with hypotension, orthostatic changes in heart rate [>20 beats per minute] or blood pressure [>20 mmHg systolic or >10 mmHg diastolic], hemoglobin drop >or=2 g/dl, or transfusion; or observed active bleeding or stigmata of hemorrhage). RESULTS We enrolled 34,701 patients with mean duration of therapy of 18 months. Rates were 0.32 and 0.38 lower GI clinical events per 100 patient-years for etoricoxib and diclofenac (hazard ratio [HR] = 0.84; 95% confidence interval [CI], 0.63-1.13). Bleeding was the most common event (rates of 0.19 and 0.23 per 100 patient-years, respectively). Multivariable analysis revealed significant risk factors to be prior lower GI event (HR = 4.06; 95% CI, 2.93-5.62) and age >or=65 years (HR = 1.98; 95% CI, 1.45-2.71). CONCLUSIONS A statistically significant decrease in lower GI clinical events was not seen with the COX-2 selective inhibitor etoricoxib versus the traditional NSAID diclofenac. The risk of a lower GI clinical event with NSAID use seems to be constant over time, and the major risk factors are a prior lower GI event and older age.

Dysplasia and Risk of Further Neoplastic Progression in a Regional Veterans Administration Barrett's Cohort

OJECTIVES:No published data are available on the risk of further neoplastic progression in Barretts patients stratified by baseline dysplasia status. Our aims were to estimate and compare the risk of progression to high-grade dysplasia or cancer in groups of Barretts patients stratified by baseline dysplasia status.METHODS:Consecutive Barretts cases from 1988–2002 were identified via pathology databases in a regional VA health-care system and medical record data were abstracted. The risk of progression to high-grade dysplasia or cancer was measured and compared in cases with versus without low-grade dysplasia within 1 yr of index endoscopy using survival analysis.RESULTS:A total of 575 Barretts cases had 2,775 patient-years of follow-up. There were 13 incident cases of high-grade dysplasia and two of cancer. The crude rate of high-grade dysplasia or cancer was 1 of 78 patient-years for those with baseline dysplasia versus 1 of 278 patient-years for those without (p = 0.001). One case of high-grade dysplasia in each group underwent successful therapy. One incident cancer case underwent successful resection and the other was unresectable. Two cases with high-grade dysplasia later developed cancer, one died postoperatively, the other was unresectable. When these two cases were included (total of four cancers), the crude rate of cancer was 1 of 274 patient-years for those with baseline dysplasia versus 1 of 1,114 patient-years for those without.CONCLUSIONS:In a large cohort study of Barretts, incident malignancy was uncommon. The rate of progression to high-grade dysplasia or cancer was significantly higher in those with baseline low-grade dysplasia. These data may warrant reevaluation of current Barretts surveillance strategies.