Endoscopic injection therapy vs. multipolar electrocoagulation vs. laser vs. injection + octreotide vs. injection + omeprazole in the treatment of bleeding peptic ulcers. A prospective randomized study

BACKGROUND/AIMS: A prospective randomized study was performed to assess the effectiveness and safety of 5 different methods of hemostasis in selected patients with high-risk bleeding peptic ulcers. METHODOLOGY: Two hundred and eight patients (n = 208; mean age: 61.6 yrs) with endoscopic stigmata of active hemorrhage, non-bleeding vessel or adherent fresh clot were randomized during emergency endoscopy to receive one of the following modalities of endoscopic therapy (with or without pharmacological therapy): I) injection of absolute alcohol (n = 44); II) multipolar electrocoagulation (BICAP; n = 42); III) Nd-YAG laser (n = 40); IV) injection of absolute ethanol + octreotide (n = 42); V) injection of absolute ethanol + omeprazole (n = 40). RESULTS: The 5 treatment groups were clinically and endoscopically comparable. The initial hemostatic success was > 90% in every group. No significant differences between groups were found in any of the following parameters assessed during hospitalization: incidence of rebleeding (I = 14.8% vs. II = 19.0% vs. III = 16.6% vs. IV = 18.1% vs. V = 20.0%; P > 0.05 mean = 17.7%); incidence of definitive hemostasis (I = 89.3% vs. II = 85.7% vs. III = 86.6% vs. IV = 84.0% vs. V = 86.6%; P > 0.05; mean = 86.5%); incidence of emergency surgery (I = 8.5% vs. II = 11.9% vs. III = 10.0% vs. IV = 6.8% vs. V = 11.1%; P > 0.05; mean = 9.6%); mortality rate (I = 4.2% vs. II = 4.7% vs. III = 3.3% vs. IV = 13.6% vs. V = 4.4%; P > 0.05; mean = 6.2%). Mean age of deceased patients was significantly higher than living patients (71.2 +/- 13.4 vs. 60.9 +/- 14.4; P < 0.05). Approximately 2/3 of the fatal cases were strongly weakened by coexistent medical diseases. The duration of hospital stay was similar for all groups. The BICAP group required less units of blood transfusion (1.9 +/- 1.8 vs. I = 3.0 +/- 2.6; III = 3.5 +/- 3.6; IV = 2.8 +/- 2.3; V = 3.1 +/- 2.5; P < 0.05), perhaps due to the higher mean value of hemoglobin of these patients at hospital admission, compared to all other groups. No significant complications were reported. CONCLUSIONS: This study provides good evidence that injection of absolute ethanol, multipolar electrocoagulation (BICAP) and Nd-YAG laser are equally safe and effective in the endoscopic therapy of acute bleeding peptic ulcers. In contrast, no additional hemostatic benefits arose from the association of pharmacological agents (octreotide or omeprazole) to sclerosis injection.     

Endoscopic hemostasis of a bleeding marginal ulcer: hemoclipping or dual therapy with epinephrine injection and heater probe thermocoagulation

BACKGROUND AND AIMS: Endoscopic hemoclipping and dual therapy with epinephrine injection and heater probe thermocoagulation have been proven effective in the hemostasis of bleeding peptic ulcers. However, the hemostatic efficacy has not been investigated in bleeding marginal ulcers. The aim of this study is to investigate the hemostatic efficacy of endoscopic hemoclipping and dual therapy with epinephrine injection and heater probe thermocoagulation in bleeding marginal ulcers. METHODS: From November 1997 to July 2000, 50 patients with active marginal ulcer bleeding underwent either hemoclipping (20 patients) or dual therapy (30 patients) for hemostasis. The demographic data, clinicopathological characteristics, endoscopic findings, initial hemostatic rates, rebleeding rates, amount of blood transfusion, the need of surgery, and mortality rates were collected and analyzed. RESULTS: Marginal ulcers were located at the anastomotic site (64%), saddle portion (22%), efferent loop (10%), or at the afferent loop (4%). The bleeding stigmata were classified into spurting artery (32%), oozing vessel (38%), visible vessel (20%), and blood clot adhesion (10%). The overall therapeutic results in 50 patients were initial hemostasis (100%), rebleeding rate (22%), need for surgery (4%), and hospital mortality rate (4%). There was no significant difference in demographic data and clinicopathological characteristics between the two modes of treatments, whereas recurrent bleeding developed in 5% in the hemoclipping group and 33% in the dual therapy group. No complication related to the procedure occurred in either mode of therapy. The hospital mortality rates were 0 and 6.7%, respectively. CONCLUSION: Endoscopy is effective in achieving initial hemostasis from bleeding marginal ulcers. However, the rebleeding rate remains high and repeated endoscopy may be needed to arrest the hemorrhage.     

Endoscopic haemoclip versus heater probe thermocoagulation plus hypertonic saline–epinephrine injection for peptic ulcer bleeding

Background. Treating patients of bleeding peptic ulcers with heater probe thermocoagulation and haemoclip is considered to be safe and very effective. Yet, there is no report comparing the haemostatic effects of endoscopic haemoclip versus heater probe thermocoagulation plus hypertonic saline–epinephrine injection in these patients.

Aim. To compare the clinical outcomes of both therapeutic modalities in patients with peptic ulcer bleeding.

Methods. A total of 93 patients with active bleeding or non-bleeding visible vessels were randomised to receive either endoscopic haemoclip (n=46) or heater probe thermocoagulation plus hypertonic saline–epinephrine injection (n=47). Five patients from the haemoclip group were excluded because of the inability to place the haemoclip.

Results. Initial haemostasis was achieved in 39 patients (95.1%) of the haemoclip group and 47 patients (100%) of the heater probe group (P>0.1). Rebleeding occurred in four patients (10.3%) of the haemoclip group and three patients (6.4%) of the heater probe group (P>0.1). The volume of blood transfused after entry into the study, duration of hospital stay, number of patients requiring urgent surgery and the mortality rates were not statistically different between the two groups.

Conclusions. If the haemoclip can be applied properly, the clinical outcomes of the haemoclip group would be similar to those of the heater probe group in patients with peptic ulcer bleeding. However, if the bleeders are located at the difficult-to-approach sites, heater probe plus hypertonic saline injection is the first choice therapy.     

Endoscopic treatment for bleeding peptic ulcers: randomised comparison of adrenaline injection and adrenaline injection + Nd:YAG laser photocoagulation.

Forty two patients with haemorrhage from peptic ulcers with visible vessels were enrolled in a randomised study comparing endoscopic haemostasis with adrenaline (1:10,000) injections (adrenaline group) and adrenaline injection + neodymium yttrium-aluminium-garnet (Nd:YAG) laser photocoagulation (adrenaline + laser group). The two groups (21 patients each) were well matched for factors affecting outcome. Surgery was performed for continued haemorrhage uncontrolled by endoscopic treatment or rebleeding after two endoscopic treatments. Haemostasis after one treatment was similar in the two groups: adrenaline 16/21 (76%), adrenaline + laser 18/21 (86%). Haemostasis after two treatments was numerically (0.05 less than p less than 0.10) greater in the adrenaline + laser group: 21/21 (100%) v 18/21 (86%). Three patients (14%) in the adrenaline group underwent uneventful emergency surgery. There were no deaths or procedure related complications in either group. Most bleeds from peptic ulcers with visible vessels can be controlled endoscopically without the need for surgery. Both treatments in this study proved highly efficacious in securing haemostasis. Adrenaline injection treatment seems to be the treatment of choice in view of its simplicity, low cost, and availability. Additional Nd:YAG laser treatment may provide a marginal improvement in efficacy, although a much larger trial would be required to prove this.     

Comparison of heater probe and YAG laser in endoscopic treatment of major bleeding from peptic ulcers

In our experience using the YAG laser and the heater probe in endoscopic treatment of major hemorrhage from peptic ulcers, ultimate hemostatic success was achieved in 19 of 20 (95%) ulcers treated with the heater probe, versus 24 of 35 (69%) YAG laser-treated ulcers (p less than 0.05). The heater probe was considerably faster, more convenient to use, and safer than YAG laser. We presently consider the heater probe to be the preferred endoscopic hemostatic device.     

Endoscopic hemostasis for bleeding peptic ulcer using a hemostatic clip or pure ethanol injection

BACKGROUND/AIMS: Endoscopic hemostasis is frequently chosen as the treatment of first choice for bleeding peptic ulcers. We retrospectively compared the hemostatic effects of hemoclips and endoscopic ethanol injection in patients with bleeding gastric and duodenal ulcers. METHODOLOGY: The subjects were 149 patients with 156 bleeding peptic ulcer lesions who were treated by endoscopic hemostasis, comprising 127 gastric ulcers and 29 duodenal ulcers. Hemoclips were used for 68 lesions (hemoclip group) and ethanol injection was done for 88 lesions (ethanol group). RESULTS: The hemostasis rates were 98.5% for the hemoclip group and 92.0% for the ethanol group. There was no significant difference in hemostatic effect between these two methods. All patients with unsuccessful hemostasis had a visible vessel larger than 2.0 mm in diameter and/or concomitant disease. CONCLUSIONS: The results suggest that these two endoscopic hemostatic methods are both highly effective. The presence of a large visible vessel may be predictive of unsuccessful hemostasis.     

钛金属夹与肾上腺素盐水注射法治疗消化性溃疡出血的对照研究

目的对照研究内镜下注射肾上腺素盐水与钛金属夹钳夹法治疗消化性溃疡出血的疗效。方法将68例消化性溃疡出血的病人(男40例,女28例,平均年龄42.62±3.57岁)分成金属夹组(n=35)和注射组(n=33),进行内镜止血治疗。结果两组病例均即时止血,两组的再出血率分别为5.71％(2/35)和9.09％(3/33)(P>0.05),两组治疗相关性并发症发生率分别为0％和42％(14/33)(P<0.01)。结论应用钛金属夹治疗上消化性溃疡出血具有设备简单、疗效好、安全性高、几无并发症等优点,值得推广应用。     

Endoscopic therapy of bleeding peptic ulcers: a cost-benefit analysis

Endoscopic hemostatic therapies have become increasingly popular and appear capable of controlling hemorrhage from peptic ulcers and reducing the need for surgery, but many physicians are unsure that the efficacy justifies the cost. In order to study this clinically and economically important issue, we developed a mathematical model to analyze the economics of endoscopic therapy of bleeding peptic ulcers. Endoscopic therapy appears capable of reducing direct hospital costs only when selectively applied to those patients with the highest risk of requiring surgery. Sensitivity analysis identifies efficacy, treatment cost, and the rebleeding rate in untreated patients as the most critical variables affecting the cost of interventional endoscopy. Using neodymium: YAG laser photocoagulation as an example, interventional endoscopy can be cost-effective for treating selected patients with bleeding peptic ulcers. Should other hemostatic devices such as the heater probe and bipolar electrocoagulator prove to be as effective as the laser, even greater cost savings could be achieved.     

Endoscopic injection sclerosis: effective treatment for bleeding peptic ulcer.

One hundred and nine patients presenting with severe haemorrhage from benign peptic ulcers were randomised to either endoscopic injection sclerotherapy using a combination of 1:100,000 adrenaline and 5% ethanolamine or to conservative treatment. Only high risk patients with active bleeding or endoscopic stigmata of recent haemorrhage and accessible ulcers were considered. The two groups were well matched for age, shock, haemoglobin concentration, endoscopic findings, and consumption of non-steroidal anti-inflammatory drugs. The group treated endoscopically had a significantly reduced rebleeding rate (12.5% v 47%, p less than 0.001). Rebleeding was successfully treated in some patients by injection sclerotherapy, other patients underwent urgent surgery. While there was a tendency towards a lower operation rate and lower transfusion requirements in the treated group, this failed to achieve statistical significance. The use of injection sclerotherapy in the conservatively treated group after rebleeding undoubtedly reduced the number of surgical operations. Endoscopic injection sclerotherapy is effective in the prevention of rebleeding in these patients.     

Prediction of therapeutic failure after adrenaline injection plus heater probe treatment in patients with bleeding peptic ulcer

BACKGROUND: Continued or recurrent bleeding after endoscopic treatment for bleeding ulcer is a major adverse prognostic factor. Identification of such ulcers may allow for alternate treatments. AIM: To determine factors predicting treatment failure with combined adrenaline injection and heater probe thermocoagulation. Methods: Consecutive patients with bleeding peptic ulcers who received endoscopic therapy between January 1995 and March 1998 were studied. Data on clinical presentation, endoscopic findings, and treatment outcomes were collected prospectively. Multiple logistic regression analysis was used to identify independent risk factors for treatment failure. RESULTS: During the study period, 3386 patients were admitted with bleeding peptic ulcers: 1144 (796 men, 348 women) with a mean age of 62.5 (SD 17.6) years required endoscopic treatment. There were 666 duodenal ulcers (58.2%), 425 gastric ulcers (37.2%), and 53 anastomotic ulcers (4.6%). Initial haemostasis was successful in 1128 patients (98.6%). Among them, 94 (8.2%) rebled in a median time of 48 hours (range 3-480). Overall failure rate was 9.6%. Mortality rate was 5% (57/1144). Multiple logistic regression analysis revealed that hypotension (odds ratio (OR) 2.21, 95% confidence interval (CI) 1.40-3.48), haemoglobin level less that 10 g/dl (OR 1.87, 95% CI 1.18-2.96), fresh blood in the stomach (OR 2.15, 95% CI 1.40-3.31), ulcer with active bleeding (OR 1.65, 95% CI 1.07-2.56), and large ulcers (OR 1.80, 95% CI 1.15-2.83) were independent factors predicting rebleeding. CONCLUSIONS: Larger ulcers with severe bleeding at presentation predict failure of endoscopic therapy.     

The management of bleeding peptic ulcer in the elderly with heater probe thermocoagulation

BACKGROUND/AIMS: The aim of this study was to compare the clinical characteristics of bleeding peptic ulcers in the elderly with those in younger patients, retrospectively. METHODOLOGY: Between 1986 and 1994, 274 patients with bleeding peptic ulcers were treated with heater probe endoscopically. They were divided into 2 groups: 48 in the elder group (70 years of age or older) and 226 in the younger group (<70). We evaluated the rate of concomitant disease, rebleeding rate, incidence of emergency surgery, mortality and blood transfusion requirement between the 2 groups. RESULTS: The incidence of concomitant disease was significantly higher in the elderly group (83.3%) than in the younger group (33.3%) (p<0.01). The rate of rebleeding (younger group 23.5% vs. elderly group 31.3%), the incidence of emergency surgery (5.8% vs. 6.3%, respectively) and the rate of mortality due to hemorrhage (2.2% vs. 4.2%, respectively) were similar in the 2 groups. There was no significant difference in the mean volume of blood transfused. CONCLUSIONS: It was revealed that aggressive endoscopic hemostasis improved the mortality rate and the incidence of emergency surgery in elderly patients as well as in younger patients, provided that their general condition was monitored carefully.     

Factors associated with failure of endoscopic injection haemostasis in bleeding peptic ulcers.

BACKGROUND: The effectiveness of a submucosal injection of adrenaline solution in endoscopic haemostasis is well documented in patients suffering from peptic ulcer bleeding. After treatment, however, a significant number of patients continue to bleed or rebleed, and require emergency surgical intervention. The aim of this study was to define factors associated with the failure of endoscopic injection haemostatic therapy in peptic ulcer bleeding. METHODS: In the period 1992 to 1998, we prospectively studied all patients suffering from peptic ulcer bleeding and identified endoscopically as being either bleeding actively or carrying a visible vessel. A total of 427 patients (343 men and 84 women; mean age 58.6 +/- 16.6 years) were all subjected to endoscopic injection with adrenaline solution on an emergency basis. Patients who eventually required surgical intervention for permanent haemostasis were considered as endoscopic haemostasis failures, whereas those who did not were considered as endoscopic treatment successes. We evaluated all clinical and endoscopic parameters that might have been related to failure of endoscopic injection therapy. RESULTS: Endoscopic injection haemostasis was successful in 341 patients (79.9%) and a failure in 86 (20.1%) who finally underwent emergency surgical haemostasis. On analysing the examined parameters, failure was significantly related to shock on admission (OR 2.31, 95% CI 1.33, 6.97), spurt bleeding at endoscopy (OR 2.45, 95% CI 1.51, 3.98), posteriorly located duodenal ulcer (OR 2.48, 95% CI 1.37, 7.01) and anastomotic ulcer (OR 3.39, 95% CI 1.37, 7.29). Endoscopic injection haemostasis therapy was less effective in patients with chronic ulcers compared to those who had acute NSAID-related ulcers. A history of peptic ulcer (OR 1.57, 95% CI 1.14, 3.05), previous peptic ulcer bleeding (OR 2.45, 95% CI 1.51, 3.98) or non-use of NSAIDs (OR 2.81, 95% CI 1.33, 4.62) were negative predictors for the outcome of endoscopic haemostasis. CONCLUSION: With the use of specific clinical and endoscopic characteristics it is possible to define a subgroup of high-risk patients for continued bleeding or rebleeding despite endoscopic injection therapy. These patients may be candidates for intensive monitoring, early surgical intervention or possibly complementary endoscopic haemostatic methods.     

Proton-pump inhibitors and outcome of endoscopic hemostasis in bleeding peptic ulcers: a series of meta-analyses

OBJECTIVE: To perform meta-analyses of studies on outcome of bleeding ulcers of different proton-pump inhibitors (PPIs) regimens, after stratification of patients by endoscopic stigmata, and analysis of studies with and without endotherapy. METHODS: A total of 35 randomized trials comparing PPIs to placebo and/or H2-receptor antagonists (H2RAs) in 4,843 patients with high-risk endoscopic stigmata were retrieved. Outcomes were rebleeding, surgery, and mortality. RESULTS: Monotherapy with oral or bolus PPIs was superior to placebo and H2RAs in reducing rebleeding in both bleeders and nonbleeders at index endoscopy; the need for surgery was reduced only when compared to H2RAs. In nonbleeders, PPI monotherapy was as effective as a combination of endotherapy with H2RAs. A combination of endotherapy with PPIs was superior to monotherapy in reducing bleeding and surgery, and superior to endotherapy alone in minimizing rebleeding, but not surgery; the benefit was lost when confronted to endotherapy plus H2RAs, whether PPIs were given as infusion or bolus. By pooling data from studies comparing high doses of PPIs as continuous infusion versus regular doses as intermittent bolus, rebleeding, surgery, and mortality were not significantly different. CONCLUSIONS: Combination of endotherapy with either PPIs or H2RAs is indicated for nonbleeding ulcers at endoscopy with the intent to reduce rebleeding and surgery. Its value may extend to bleeding lesions, but current data are scanty. The benefit appears to be independent from route and doses of PPIs, as oral, bolus, or infusional methods are all effective.     

Comparison of endoscopic injection therapy versus the heater probe in major peptic ulcer haemorrhage.

One hundred and twenty patients presenting with major peptic ulcer haemorrhage were randomised in a clinical trial comparing endoscopic injection and heater probe therapy. The two groups were well matched with regards to age, admission haemoglobin concentration, the presence of shock, non-steroidal anti-inflammatory drug usage and endoscopic findings. Permanent haemostasis was achieved in 87% of the injection group and 85% of the heater probe group. Hospital mortality, transfusion requirement and duration of admission were similar in both groups. Endoscopic injection and the heater probe represent equally effective therapy for peptic ulcer bleeding.     

Randomized controlled trial comparing epinephrine injection plus heat probe coagulation versus epinephrine injection plus argon plasma coagulation for bleeding peptic ulcers

BACKGROUND: Epinephrine injection with heat probe coagulation is an effective treatment for bleeding peptic ulcer. Few studies have investigated the efficacy of dual therapy with epinephrine injection plus either heat probe or argon plasma coagulation for high-risk bleeding peptic ulcers. This study compared epinephrine injection plus heat probe coagulation to epinephrine injection plus argon plasma coagulation for the treatment of high-risk bleeding peptic ulcers. METHODS: The study design was prospective, randomized, and controlled. Patients with actively bleeding peptic ulcers, ulcers with adherent clots, or ulcers with nonbleeding visible vessels were randomly assigned to epinephrine injection plus heat probe coagulation or epinephrine injection plus argon plasma coagulation. Patients with previous gastric surgery, malignant ulcers, and unidentifiable ulcers because of torrential bleeding were excluded. The primary outcome measure was recurrence of bleeding. Secondary outcome measures were initial hemostasis, endoscopic procedure duration, number of patients requiring surgery, mortality within 30 days, and ulcer status at 8 week follow-up endoscopy. RESULTS: One hundred ninety-two patients were enrolled; 7 with malignant ulcers were excluded after randomization. One hundred eighty-five cases were analyzed, 97 in the heat probe group and 88 in the argon plasma coagulation group. Patient demographics and ulcer characteristics were comparable between the groups. There was no significant difference in terms of initial hemostasis (95.9% vs. 97.7%), frequency of recurrent bleeding (21.6% vs. 17.0%), requirement for emergency surgery (9.3% vs. 4.5%), mean number of units of blood transfused (2.4 vs. 1.7 units), mean hospital stay (8.2 vs. 7.0 days), and hospital mortality (6.2% vs. 5.7%). Sixty (61.8%) patients in the heat probe group and 52 (52.9%) in the argon plasma coagulation group underwent endoscopy at 8 weeks. There was no significant difference between these groups in the relative frequency of nonhealing ulcer at 8 weeks. CONCLUSION: Epinephrine injection plus argon plasma coagulation is as safe and effective as epinephrine injection plus heat probe coagulation in the treatment of patients with high-risk bleeding peptic ulcers.     

Intravenous pantoprazole versus ranitidine for prevention of rebleeding after endoscopic hemostasis of bleeding peptic ulcers

AIM: The role of intravenous pantoprazole in treatment of patients with high-risk bleeding peptic ulcers following endoscopic hemostasis remains uncertain. We therefore conducted the pilot prospective randomized study to assess whether intravenous pantoprazole could improve the efficacy of H(2)-antagonist as an adjunct treatment following endoscopic injection therapy for bleeding ulcers. METHODS: Patients with active bleeding ulcers or ulcers with major signs of recent bleeding were treated with distilled water injection. After hemostasis was achieved, they were randomly assigned to receive intravenous pantoprazole or ranitidine. RESULTS: One hundred and two patients were enrolled in this prospective trial. Bleeding recurred in 2 patients (4%) in the pantoprazole group (n = 52), as compared with 8 (16%) in the ranitidine group (n = 50). The rebleeding rate was significantly lower in the pantoprazole group (P = 0.04). There were no statistically significant differences between the groups with regard to the need for emergency surgery (0% vs 2%), transfusion requirements (4.9+/-5.9 vs 5.7+/-6.8 units), hospital days (5.9+/-3.2 vs 7.5+/-5.0 d) or mortality (2% vs 2%). CONCLUSION: Pantoprozole is superior to ranitidine as an adjunct treatment to endoscopic injection therapy in high-risk bleeding ulcers.     

Endoscopic sclerosis in the treatment of bleeding peptic ulcers with a visible vessel

We have assessed the efficacy of endoscopic sclerosis in the routine clinical management of patients with bleeding ulcers, in whom a visible vessel was identified at endoscopy. Over a period of 14 months, a visible vessel at the base of an ulcer was identified in 53 patients. Three patients could not undergo sclerosis, one because of torrential bleeding and two because of ulcer location. Fifty patients, 18 with a bleeding vessel and 32 with a nonbleeding vessel, were subjected to endoscopic sclerosis with adrenaline plus polidocanol. Permanent hemostasis was achieved in 45 patients (90%), 31 (62%) cases with one session and 14 (28%) cases with two sessions of sclerosis. Four patients had persistent rebleeding in spite of two sessions of sclerosis, and one patient had a massive rebleeding after the first session; all underwent emergency surgery. We believe that endoscopic sclerosis has a primary role in the treatment of ulcer bleeding, particularly in those patients in whom a visible vessel is identified at endoscopy.