Curr Gastroenterol Rep (2011) 13:525–531 527 Fig. 1 Forrest Ia ulcer bleeding in a small gastric ulcer high risk of recurrent bleeding with medical therapy alone. In contrast, ulcers with a clean base or flat spot in the ulcer bed (resp. Forrest III and IIc) do only rebleed in 4% to 13% of cases [16]. Ulcers with adherent clots have an intermediate risk of rebleeding (about 25%), depending on the underlying lesion. For that reason, clot removal should be attempted by vigorous irrigation. Endoscopic haemostatic therapy is indicated for patients with high risk ulcers, while patients with low-risk stigmata can be treated with pharmacotherapy alone. The optimal manage- ment of bleeding peptic ulcers with adherent clot remains controversial. Two meta-analyses have addressed this issue. The first included six studies involving 240 patients from the United States, Southeast Asia, and Europe and found a significantly lower risk of rebleeding in the patients who underwent endoscopic therapy compared with the medical therapy group (8 vs. 25%, P=0.01). The interventions yielded similar results with respect to the need for surgery, transfusion requirement, length of hospital stay and mortality [17]. The validity of this meta-analysis was however questioned since studies with heterogeneous designs were combined and most studies used suboptimal PPI dosage in the control group [18]. A more recent meta-analysis, including five trials, comprising 189 patients, found no significant benefit of endoscopic therapy in patients with ulcers with adherent clots [19 ]. So far, endoscopic therapy should be considered, although intensive PPI therapy may be sufficient among patients with adherent clots resistant to vigorous irrigation. Injection Therapy Injection therapy with epinephrine is widely used for the treatment of PUB because it is inexpensive, easy to administer, and effective. Acute hemostasis is achieved by local tamponade, vasospasm, and induction of thrombosis. These effects resolve after about 20 min and it is therefore recommended to combine injection therapy with a more durable endoscopic technique [10 ]. Other substances used in addition to or as an alternative to epinephrine are sclerosants (eg polidocanol, ethanolamine, and ethanol), fibrin sealant, and on some occasions n-butyl cyanoacrylate. However, the use of sclerosants for the treatment of PUB is nowadays limited, because they can cause serious local side-effects and in addition to epinephrine confer minimal additional benefit [20]. Fibrin sealant or glue is a relatively new agent for the treatment of PUB. It was shown to be more effective in preventing rebleeding than injection with polidocanol, but only if repeatedly injected [21]. Also, for that reason, it is not generally used in clinical practice. N-butyl cyanoacrylate is in particular used for gastric variceal bleeds, but is on rare occasions also applied to bleeding peptic ulcers with massive bleeds as a last resort, with the risk of arterial embolization [22]. Ablative and Mechanical Therapies Several meta-analyses compared the effects of mechanical therapies (eg hemoclip placement), ablative therapy (eg heater probe and Gold probe), and injection therapy (eg epinephrine, fibrin glue and sclerosants) for hemostasis and prevention of rebleeding in peptic ulcer bleeding [19 , 23–26] (Table 1). This yielded two important messages. The first is that although epinephrine injection is more effective than acid suppressive therapy alone in patients with high risk stigmata, epinephrine monotherapy is inferior to other monotherapies as well as to combination therapy [19 , 23–25]. This means that epine- phrine should no longer be applied as monotherapy, but only in combination with other methods. The second major message from the meta-analyses was that none of the ablative or mechanical therapies were superior over the others. Dual therapy (ie epinephrine injection plus other injection or thermal or mechanical method) proved signif- icantly superior to epinephrine injection alone, but had no advantage over thermal or mechanical monotherapy [23]. In specific situations, eg difficult-to-approach or indi- rectly visualized bleeding sites, heater probe therapy can be superior to hemoclip placement [27]. Hemospray A potentially very important new development is the intro- duction of a hemospray which can be directly applied via a catheter through the working channel. This nanopowder with clotting abilities has been shown to be highly effective for achieving hemostasis of arterial bleeding in a heparinized animal model. When sprayed on a bleeding site, the powder becomes cohesive and adhesive, and forms a stable mechanical