Is the Forrest classification a useful tool for planning endoscopic therapy of bleeding peptic ulcers?

A prospective controlled study was carried out to determine the validity of the Forrest classification in terms of improved laser therapy. Out of 153 consecutive patients with bleeding peptic ulcers, 137 patients--74 with arterial ulcer bleeding and 63 with non-arterial ulcer bleeding--were included in the trial. In arterial ulcer bleeding a significantly lower rate of permanent hemostasis was achieved, and the frequency of urgent surgery and mortality was higher than in non-arterial ulcer bleeding. Patients with spurting arterial bleeding (Forrest Ia) and those with large non-bleeding visible vessels (Forrest IIa) include almost all patients at risk of further bleeding and death. Combined laser therapy clearly minimizes the risk of rebleeding and death in small non-bleeding visible vessels (Forrest IIa). In contrast, decreased hemoglobin and a requirement for blood transfusion are of limited prospective value for the individual emergency patient. Overall, our results demonstrate that Forrest criteria are essential for proper planning of endoscopic therapy and urgent surgery in bleeding peptic ulcers. Emergency endoscopy must therefore be performed as early as possible.     

Life-threatening intraabdominal arterial embolization after histoacryl injection for bleeding gastric ulcer

N-butyl-cyanoacrylate (Histoacryl) injection has become the treatment of choice for acutely bleeding esophagogastric varices, and is the only effective option for endoscopic treatment of gastric varices. Recent reports confirm the ability of Histoacryl injection therapy to achieve immediate hemostasis in cases of gastric ulcer bleeding or Dieulafoy ulcer, where conventional endoscopic hemostatic treatment had failed. Although the overall safety record of Histoacryl injection has been relatively good, there have been scattered cases of serious complications. Here, we present two patients showing life-threatening intraabdominal arterial embolization after Histoacryl injection. They had chronic gastric ulcers with active arterial bleeding. In spite of attempts at hemostatic treatment, complete hemostasis was not achieved. We injected Histoacryl, diluted with Lipiodol, into bleeding gastric ulcers, resulting in successful hemostasis. Soon after the procedure, intraabdominal arterial embolization developed in both patients. One patient survived and the other died. Based on these experiences, we would like to warn gastrointestinal endoscopists to be alert to these fatal complications, and we propose that less diluted Histoacryl seems to be preferable in cases of bleeding peptic ulcers.     

Local epinephrine injection improves the therapeutic effect of Nd-YAG laser treatment of arterial peptic ulcer bleeding

Nd-YAG laser therapy has been shown to be effective in the treatment of gastrointestinal ulcer bleeding. However, a breakdown by bleeding severity shows that its benefit is doubtful in bleeds classified as Forrest Ia and IIa. In a prospective study, we therefore tested a new therapeutic approach combining epinephrine injection into the bleeding site, with subsequent laser coagulation. Thirty-two patients with Forrest Ia and IIa bleeding from gastric or small intestinal ulcers were compared with 51 own historical controls treated by laser coagulation alone. In the combined therapy group, a significantly higher rate of permanent hemostasis was achieved, and mortality and frequency of emergency surgery were significantly reduced. Furthermore bleeding recurred more rarely and only during the later course of the disease. Finally, following epinephrine injection fewer Forrest IIa ulcer bleeds were reactivated by laser treatment, and all of these bleeds were stopped by further laser coagulation. Overall, our results demonstrate a clear-cut therapeutic improvement when laser coagulation is preceded by local epinephrine injection.     

New endoscopic hemostasis methods

Endoscopic treatment for non-variceal upper gastrointestinal bleeding has evolved over decades. Injection with diluted epinephrine is considered as a less than adequate treatment, and the current standard therapy should include second modality if epinephrine injection is used initially. Definitive hemostasis rate following mono-therapy with either thermo-coagulation or hemo-clipping compares favorably with dual therapies. The use of adsorptive powder (Hemo-spray) is a promising treatment although it needs comparative studies between hemospray and other modalities. Stronger hemo-clips with better torque control and wider span are now available. Over-the-scope clips capture a large amount of tissue and may prove useful in refractory bleeding. Experimental treatments include an endoscopic stitch device to over-sew the bleeding lesion and targeted therapy to the sub-serosal bleeding artery as guided by echo-endoscopy. Angiographic embolization of bleeding artery should be considered in chronic ulcers that fail endoscopic treatment especially in elderly patients with a major bleed manifested in hypotension.     

Risk assessment and prediction of rebleeding in bleeding gastroduodenal ulcer

BACKGROUND AND STUDY AIMS: The aims of this study were to identify risk factors for recurrence of hemorrhage in bleeding gastroduodenal ulcers after endoscopic injection therapy, and to develop a simple and relevant prognostic score which could be used to assess the early risk of recurrence and the residual risk of rebleeding. PATIENTS AND METHODS: A prospective study was conducted from January 1995 to December 1998, in 738 patients who were admitted to our department for acute bleeding peptic ulcer and who underwent endoscopic examination. Ulcers with active bleeding or signs of recent bleeding were treated with injection therapy using epinephrine (1/10,000) and 1% polidocanol. RESULTS: Multivariate analysis revealed that liver cirrhosis, recent surgery, systolic blood pressure below 100 mmHg, hematemesis, Forrest classification, and ulcer size and site were significantly predictive variables for the recurrence of hemorrhage. Among these, Forrest classification was the most important. The overall accuracy of the predictive model was 71% (95% CI = 63 - 79%). The model showed a better sensitivity of 90% for early rebleeding (< 48 hours) than for late rebleeding (> or = 48 hours) where the sensitivity was 65 %. A prognostic score was obtained and patients were classified into four risk classes: very low (VL), low (L), high (H), and very high (VH). The rebleeding rates for the four classes were 0%, 7.9%, 31.8% and 67.9%, and the mortality rates were 5.9%, 8.6%, 13.9% and 35.7%, respectively. The residual risk of rebleeding after 48 hours was 0%, 3.3%, 10.4%, and 14.3% in the VL, L, H and VH classes, respectively. After 5 days the residual risk was under 4% in all classes. CONCLUSIONS: This study demonstrates that the proposed prognostic score, which is easily obtained after emergency endoscopy, is useful in clinical practice because it can identify patients with different levels of rebleeding risk. It can be helpful in patient management and decision making for discharge.     

Site and size of bleeding peptic ulcer. Is there any relation to the efficacy of hemostatic sclerotherapy?

In 78 patients with high-risk bleeding peptic ulcers (either with active bleeding or non-bleeding visible vessel) endoscopic hemostasis by injection of adrenaline and polidocanol was attempted. Sclerotherapy was performed in 70 (90%) patients. Initial hemostasis was achieved in 35 (94.5%) patients with active bleeding, and permanent hemostasis in 61 (87%). Efficacy of injection therapy was significantly lower in ulcers larger than 2 cm (p = 0.001), and in those located on the posteroinferior duodenal wall (p = 0.03). It was not possible to perform endoscopic injection in 8 (10%) patients due to difficulty of access, lesions located mainly high on the lesser gastric curvature and on the posteroinferior duodenal wall. From these results we conclude that endoscopic injection is a very useful technique for the initial treatment of high-risk bleeding peptic ulcer, although the size and anatomical location of the lesions may be a limitation of its use.     

Ulcers and nonvariceal bleeding

Peptic ulcer remains the commonest and most significant cause of nonvariceal upper gastrointestinal bleeding. The incidence of peptic ulcer bleeding is rising in elderly patients, particularly for duodenal ulcer. Patients presenting with upper gastrointestinal bleeding who have low Rockall scores are at low risk of rebleeding and death. These patients currently utilize considerable health-care resources, but could safely be managed at home. The Rockall score can be used to predict the risk of rebleeding and death following variceal bleeding, but for patients with ulcer bleeding, its ability to predict death is questioned. Acid suppression is effective in preventing rebleeding from peptic ulcer. Standard doses of intravenous omeprazole may be as effective as high-dose regimens. Oral omeprazole also reduces rebleeding following endoscopic therapy for peptic ulcer. Mallory-Weiss tears result in significant bleeding in 23 % of cases. Endoscopic therapy may only be required in cases in which active bleeding is present. Endoscopic therapy is effective and safe in patients with major peptic ulcer bleeding who are over 80 years old. For peptic ulcer, injection of larger volumes of epinephrine (adrenaline; mean 16.5 ml) are more effective than small volumes (mean 8 ml). Injection of normal saline alone is less effective than bipolar electrocoagulation. The addition of fibrin glue to epinephrine injection does not confer an additional benefit over epinephrine alone. Argon plasma coagulation can be used to treat a range of lesions in the gastrointestinal tract. It is also effective for treatment of bleeding ulcer, but is no better than established methods. Haemoclips may be useful in bleeding Mallory-Weiss tears, but their use is difficult in patients bleeding from peptic ulcer. The presence of a large ulcer and active bleeding at the time of endoscopy are independent predictors of failure of endoscopic therapy.     

Safety and tolerability of high-dose intravenous esomeprazole for prevention of peptic ulcer rebleeding

Introduction  

Efficacy of a continuous high-dose intravenous infusion of esomeprazole, followed by an oral regimen after successful endoscopic therapy for peptic ulcer bleeding (PUB) was established in the PUB study (ClinicalTrials. gov identifier: NCT00251979). Mortality rates and detailed safety and tolerability results from this study are reported here.     

Injection therapy of bleeding peptic ulcer. A prospective, randomized trial using epinephrine and thrombin

A prospective randomized trial involving 64 patients with bleeding peptic ulcers was performed to assess the efficacy of two modalities of injection therapy. The inclusion criterion was the presence of active bleeding or a visible vessel at emergency endoscopy. Thirty-two patients were treated with epinephrine (Group A) and 32 with epinephrine plus thrombin (Group B). Permanent hemostasis was achieved in 81.3% Group A, and 84.4% Group B patients, and therapy failures occurred in 18.6% and 15.6%, respectively. Mortality was nil in both groups. There were no differences in the requirement for emergency surgery, or in the number of transfusions in the two groups. A second elective endoscopy was performed in 49 patients between the 3rd and the 5th day after admission, proceeding to a second injection therapy if a visible vessel was still seen. There were no failures among re-injected patients. With one exception, none of the failures occurred in patients in whom a second endoscopy was done. Our results suggest that injection therapy, which is a simple technique, should be considered as the initial treatment of choice in bleeding peptic ulcer. The addition of thrombin to epinephrine does not improve the results of the method. An early second endoscopy and local therapy if a visible vessel is still present, may further improve the results.     

Endoscopic hemostasis by local injection of epinephrine and polidocanol in bleeding ulcer. A prospective randomized trial

The present prospective randomized trial has been carried out to assess the efficacy of the endoscopic injection of epinephrine plus polidocanol, in the prompt treatment of upper gastrointestinal bleeding due to peptic lesions. Over a period of one year, 72 patients were admitted to the study. Thirty-six of these underwent endoscopic treatment (group A), while the others received medical treatment (group B). Definitive hemostasis was achieved in 29 patients in group A, and in 21 in group B (p less than 0.05). Seven patients in group A and 12 in group B underwent emergency surgery for persistent or recurrent bleeding (p = NS). Three patients from group B received endoscopic treatment owing to relative surgical contraindications. It was successful in all of them. Patients from group A needed a significantly lower number of units of packed red cells (p less than 0.05). Our results show that it is justified to employ endoscopic injection as the first therapeutic step in upper GI bleeding due to peptic gastroduodenal lesions.     

Endoscopic factors predisposing to rebleeding following endoscopic hemostasis in bleeding peptic ulcers.

BACKGROUND AND STUDY AIMS: Various clinical and endoscopic factors have been proposed and used as predictors of endoscopic treatment failure in bleeding peptic ulcers. Recently, several endoscopic factors have been considered to be more significant than various clinical factors, except for shock. Detailed knowledge of which endoscopic factors can be classified as predictors of rebleeding following endoscopic hemostasis is needed. This study describes newly defined endoscopic variables and evaluates their usefulness as predictors of endoscopic treatment failure. PATIENTS AND METHODS: Between January 1996 and April 1999, diagnostic and therapeutic endoscopies were carried out in 143 patients with active bleeding peptic ulcers. Nine clinical and eight endoscopic variables were studied. Endoscopic factors were classified by three types of stigmata bleeding, 14 locations, two ulcer sizes, three ulcer bases, three visible vessel colors, two ulcer depths, two margin shapes, and three endoscopic treatment methods (injection, hemoclipping, and combination). RESULTS: 36 patients experienced rebleeding (25.2 %), 11 patients needed operations (7.7 %) and five deaths occurred (3.5 %). In univariate analysis, rebleeding was significantly related to: i) presence of spurting activity (odds ratio [OR] = 4.91, P = 0.006), ii) ulcer size larger than 2 cm (OR = 2.78, P = 0.017); and iii) location in stomach (OR = 2.81, P = 0.026). Clinical variables including age, shock, and initial hemoglobin levels were not significantly related to rebleeding. In multiple logistic regression using selected significant variables, presence of spurting activity remained a significant independent predictor of rebleeding (adjusted OR = 6.48, P = 0.003). CONCLUSION: Our data support the hypothesis that endoscopic factors are more important than clinical ones when predicting rebleeding of peptic ulcers. Based on statistical analysis of risk factors, the ulcers most likely to rebleed after endoscopic therapy are those which are located in the stomach, are greater than 2 cm in diameter and exhibit oozing or spurting of blood.     

Esophageal visible vessel as a cause of massive upper gastrointestinal hemorrhage

Besides peptic ulcers, erosions, esophageal varices, tumors and non-variceal esophageal lesions, vascular abnormalities lead to an upper gastrointestinal hemorrhage in 1-5% of cases. Among 581 emergency esophagogastro-duodenoscopies for acute gastrointestinal bleeding performed in our institution between 1987 and 1989, an esophageal visible vessel was found to be the source of massive hemorrhage in five patients. All patients were males with ages ranging from 37 to 84 years. Esophageal visible vessel was localized in one patient in the middle third and in four patients in the distal portion of the esophagus. Using the Forrest classification, endoscopy revealed an oozing hemorrhage (Ib) in two patients and a protruding vessel (IIa) in three patients. Definitive hemostasis could be achieved in all patients by local injection of adrenaline combined with heater probe thermocoagulation. In some patients with recurrent upper gastrointestinal bleeding, visible esophageal vessel is a rare source of bleeding that has not yet been described.     

Diagnosis and management of upper gastrointestinal bleeding

Upper gastrointestinal bleeding causes significant morbidity and mortality in the United States, and has been associated with increasing nonsteroidal anti-inflammatory drug use and the high prevalence of Helicobacter pylori infection in patients with peptic ulcer bleeding. Rapid assessment and resuscitation should precede the diagnostic evaluation in unstable patients with severe bleeding. Risk stratification is based on clinical assessment and endoscopic findings. Early upper endoscopy (within 24 hours of presentation) is recommended in most patients because it confirms the diagnosis and allows for targeted endoscopic treatment, including epinephrine injection, thermocoagulation, application of clips, and banding. Endoscopic therapy results in reduced morbidity, hospital stays, risk of recurrent bleeding, and need for surgery. Although administration of proton pump inhibitors does not decrease mortality, risk of rebleeding, or need for surgery, it reduces stigmata of recent hemorrhage and the need for endoscopic therapy. Despite successful endoscopic therapy, rebleeding can occur in 10 to 20 percent of patients; a second attempt at endoscopic therapy is recommended in these patients. Arteriography with embolization or surgery may be needed if there is persistent and severe bleeding.     

Management in peptic ulcer hemorrhage: a Dutch national inquiry

BACKGROUND AND STUDY AIMS: There is no consensus as to what endoscopic hemostatic therapy and pharmacotherapy should be used in peptic ulcer hemorrhage (PUH). We conducted a mail survey to investigate current management of ulcer hemorrhage in the Netherlands. METHODS: A questionnaire was sent to gastroenterologists or, if not present, to internists, performing endoscopies, in every hospital in the Netherlands (n = 123). Endoscopic hemostatic therapy, pharmacotherapy, endoscopic reintervention, and management of Helicobacter pylori were evaluated. RESULTS: 90/123 (73%) questionnaires were returned. Endoscopic hemostatic therapy is given in ulcers classified as Forrest Ia, Ib, IIa, IIb, and IIc by, respectively, 89%, 93%, 83%, 47%, and 19% of respondents. Gastroenterologists perform endoscopic therapy more often in Forrest Ib (P=0.03), IIa (P=0.002), and IIb (P=0.001) ulcers when compared with internists. Endoscopic injection therapy is used by 93% of respondents as first modality. Epinephrine combined with polidocanol is most commonly used (60%). Pharmacotherapy is given by 97%. A total of 71% use proton pump inhibitors (PPIs), and 26% use H2-receptor antagonists (H2RAs), both mainly initially given intravenously. In case of suspected rebleeding, endoscopic reintervention is performed by 76%, including a significantly greater percentage of gastroenterologists (89% of gastroenterologists vs. 60% of internists, P=0.005), whereas the others refer the patient directly for surgery. Almost all respondents investigate for H. pylori. Eradication is confirmed by only 64% (80% of gastroenterologists vs. 50% of internists, P=0.004). CONCLUSIONS: There are important differences in management of peptic ulcer hemorrhage between gastroenterologists and internists in the Netherlands. Management is only partly in accordance with evidence-based medicine.     

Randomized trial of N-butyl-2-cyanoacrylate compared with injection of hypertonic saline-epinephrine in the endoscopic treatment of bleeding peptic ulcers

BACKGROUND AND STUDY AIMS: Theoretically, the injection of cyanoacrylate may be effective for peptic ulcer bleeding, but randomized clinical trials are rare. The aim of this study was to compare the efficacy of N-butyl-2-cyanoacrylate (Histoacryl) and hypertonic saline-epinephrine (HSE) in the endoscopic treatment of major peptic ulcer hemorrhage. PATIENTS AND METHODS: A total of 126 patients with major peptic ulcer hemorrhage and active bleeding or a nonbleeding visible vessel were randomly allocated to endoscopic injection with HSE (63 patients; group 1) or to injection with Histoacryl (63 patients; group 2). The two groups were well matched for age, sex, initial hemoglobin values, ulcer size and location, and bleeding stigmata. RESULTS: Initial hemostasis was achieved in 58 cases (92.1%) in group 1 and in 60 cases (95.2%) in group 2 (P=0.717). Rebleeding rates were 16 of 58 in group 1 and seven of 60 in group 2 (P=0.051). There were no significant differences regarding the rates of permanent hemostasis (51 of 63 in group 1 vs. 57 of 63 in group 2, P=0.203), emergency surgery (seven of 58 in group 1 vs. three of 60 in group 2, P=0.200), or hospital mortality due to bleeding (0 in group 1 and 0 in group 2). With regard to the rebleeding rate, there was a significant difference between group 1 and group 2 in the subgroup with active arterial bleeding (11 of 26 in group 1 and four of 29 in group 2, P=0.039) but not in the subgroup with a nonbleeding visible vessel (five of 32 in group 1 and three of 31 in group 2, P=0.708). There were no statistically significant differences in hemostatic results between the two treatment groups in the subgroups with gastric ulcers or duodenal ulcers. Although no complications followed HSE therapy, arterial embolization with infarction occurred in two patients in the Histoacryl group, of whom one died. CONCLUSIONS: Compared with HSE injection, Histoacryl injection showed no statistically significant differences in hemostatic results, except for decreasing the rebleeding rate in the patients with active arterial bleeding. However, the use of Histoacryl to control peptic ulcer bleeding should be reserved as a last resort before surgery, because of possible embolic complication.     

Helicobacter pylori infection does not affect the early rebleeding rate in patients with peptic ulcer bleeding after successful endoscopic hemostasis: a prospective single-center trial

BACKGROUND AND STUDY AIMS: Eradication of Helicobacter pylori infection can reduce the rebleeding rate of peptic ulcer bleeding in the long term. There are few data on the influence of H. pylori on the rebleeding rate in the acute phase of bleeding however. We therefore prospectively investigated the influence of H. pylori infection on the early rebleeding rate in patients who had undergone successful endoscopic hemostasis treatment for peptic ulcer bleeding. PATIENTS AND METHODS: Between January 1996 and November 2000 all patients with peptic ulcer bleeding were evaluated consecutively. The diagnosis of H. pylori infection was made at index endoscopy, using histology and the rapid urease test. Bleeding activity was assessed using the Forrest classification. After successful endoscopic hemostasis all patients received omeprazole 40 mg or pantoprazole 40 mg, intravenously, twice a day for 3 days. Rebleeding episodes were recorded over 21 days following primary hemostasis. RESULTS: 344 patients were enrolled into the study. The prevalence of H. pylori infection was 62.9 %. A total of 51 patients showed rebleeding (14.8 %), of whom 31 were H. pylori-positive (60 %). There was no statistically significant difference between the H. pylori-positive and -negative patients, however. The rebleeding rate did not differ between patients with H. pylori infection alone and patients also using nonsteroidal anti-inflammatory drugs. When stratifying patients according to activity of bleeding at index endoscopy, we were also unable to find any significant influence of H. pylori infection on the outcome of Forrest class I and IIa bleedings. CONCLUSION: Based on our data, it can be concluded that H. pylori infection does not affect the early rebleeding rate in patients with peptic ulcer bleeding after successful endoscopic hemostasis.     

Endoscopic hemostasis by injection therapy and electro-hydro-coagulation in high-risk patients with active gastroduodenal bleeding ulcer

For the purpose of arresting hemorrhage from bleeding gastric or duodenal ulcers we developed, in 28 high-risk patients, a new method of endoscopic local injection of epinephrine (1:10,000) followed by electro-hydro monopolar coagulation and injection of Polidocanol (1%). Nine patients had signs of shock at the time of admission. The average blood requirements were 3.9 units in the first 24 hours. All patients had important factors militating against surgery, namely age and serious primary disease. In 26 out of 28 patients (92.8%) hemostasis was accomplished during endoscopy. Three patients (10.7%) rebled within the first 36 hours, requiring emergency surgery. Thus definitive hemostasis was achieved in 23 patients (82.1%). There were no complications as a result of endoscopic treatment.     

消化性溃疡出血内镜下注射治疗后再出血的危险因素探讨

目的：探讨消化性溃疡出血内镜注射止血后再出血可能的危险因素。方法：对23例一周内再出血及135例无再出血患者的临床及内镜表现特征进行单因素非条件logistic回归分析，在此基础上进一步进行多因素的logistic回归分析。结果：单因素分析有显著意义的变量为入院时休克、血红蛋白浓度、血尿素氮浓度、内镜下喷血表现、内镜下渗血表现。多因素非条件logistic回归分析发现，再出血与入院时休克、内镜下喷血、内镜下渗血相关有显著性意义。结论：入院时休克、内镜下活动性出血是内镜注射治疗后再出血的独立危险因素。     

Injection of nonvariceal bleeding lesions of the upper gastrointestinal tract

In a prospective series 102 non-variceal upper GI bleeders were studied. An indication for endoscopic injection therapy was seen in 63 patients. In accordance with bleeding intensity, 27 patients were grouped as Forrest Ia, 37 as Forrest Ib, 8 as Forrest II with a "visible vessel" and 13 as Forrest II without one. Definitive hemostasis was achieved in almost 100% of the cases. Within the Forrest Ia group mortality was lowered to 11% as compared with 20% within the emergency surgery group. More than 80% of patients had at least one severe coexistent illness. The aim of endoscopic injection is to avoid surgery in high-risk patients.     

The effect of endoscopic hemostasis with alcohol on the mortality rate of nonvariceal upper gastrointestinal hemorrhage. A randomized prospective study

One hundred and forty-five patients with nonvariceal upper GI hemorrhage, active or with stigmata (Forrest I and II) were divided into two groups according to the day of the week on which emergency endoscopy was performed: group A (78 patients) in which conventional treatment was applied (blood transfusions, antacids, cimetidine, pirenzepine), and group B (65 patients) in which endoscopic hemostasis with absolute alcohol (Asaki's method) was performed. The two groups were comparable as regards age, sex distribution and type of hemorrhage (after Forrest). Emergency surgery was performed in both groups if the bleeding did not stop or if it recurred. Twenty patients (11 in group A and 9 in group B) were operated on some time after the bleeding episode (5-18 days) to prevent new episodes. Absolute alcohol injection achieved hemostasis in all the cases of active hemorrhage (Forrest I) and prevented recurrence in 24 out of 25 cases with a clot or visible vessels (Forrest II), so that emergency surgery was not necessary in any of the patients of group B. Mortality rate was significantly lower in group B than in group A (10 deaths in group A, 2 in group B, p less than 0.05) being explained mainly by the reduced post-operative mortality (18% in group B), due to the small number of the operated patients (28 in groups A, 10 in B; p less than 0.02), especially of those operated on as an emergency (one in the endoscopic hemostasis group as compared with 17 in the conventional treatment group; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)