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Dieulafoy's lesion
Dieulafoy's lesion Yuk Tong Lee, MRCP, MD, Russell S. Walmsley, MRCP, MD, Rupert W. L. Leong, FRACP, MBBS, Joseph J.Y. Sung, MD, PhD, FRCP, FACG Hong Kong, China, Auckland, New Zealand
Dieulafoy's lesion (DL), also know as cirsoid aneurysm I and submucosal arterial malformation,2 was originally described by Gallard in 1884 and designated "exulceratio simplex" by the French surgeon Georges Dieulafoy 14 years later.3, 4 Dieulafoy believed that the lesion was the first stage of a gastric ulcer, the progression of which was interrupted by the occurrence of bleeding. Advances in endoscopic therapeutic methods have greatly decreased the associated mortality, but DL remains one of the most difficult diagnoses and somewhat of a pathologic puzzle.
PATHOLOGY Histologically, DL consists of an abnormal, submucosal "caliber-persistent artery" that typically protrudes through a minute 2- to 5-mm mucosal defect. The submucosal artery fails to undergo the usual ramification within the wall of the stomach or to diminish to the minute size of the mucosal capillary microvasculature.5,6 The diameter of the caliber-persistent artery at the muscularis mucosae level can range from 1 to 3 ram, almost 10 times the diameter of normal arteries at the same level (Fig. 1). 5,7 Histologically, there is subintimal fibrosis of the artery, but there is no true structural aneurysmal change. 5 Importantly, there is an absence of inflammation at the edge of the mucosal defect in contrast to that present in peptic ulcer disease. The tortuous arteries are accompanied by large veins, which Miko and Thomazy5 found to have led to both arterial and venous rupture in three fourths of the 24 pathology specimens examined. Intimal thickenCurrent affiliations: Departments of Medicine and Therapeutics, Prince of Wales Hospital, Chinese University of Hong Kong, Shatin, Hong Kong, Department of Gastroenterology, North Shore Hospital, Auckland, New Zealand. Dr. Walmsley is in receipt of a personal grant from the Genesis Oncology Trust, New Zealand. Reprint requests: Yuk Tong Lee, MD, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, N.T Hong Kong, China. Copyright 9 2003 by the American Society for Gastrointestinal Endoscopy 0016-5107/2003/$30.00 + 0 doi:l O.1067/ mge.2003.328 236
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Figure 1. Photomicrographof histologicsectionshowingcaliber persistentartery tracking through gastric submucosa (H&E, orig.mag.x 125). ing occurs in both veins and arteries with thrombosis formation, but the mechanism of final rupture of the vessel is uncertain.5,8 The very first case description of this phenomenon was that of Gallard in 1884. Dieulafoy reported 3 of his own cases and identified 4 further cases in other publications. Dieulafoy found what he termed "miliary abscesses," which he believed perforated into the gastric lumen and exposed the normal blood vessels beneath to peptic digestion. He surmised this was the presentation of a nascent common type gastric ulcer and so coined the term "exulceratio simplex." Modem pathologists have proposed that bleeding occurs as a result of pressure erosion of the overlying epithelium by the ectatic vessel. 2 Miko and Thomazy5 suggested that these anomalous vessels are abnormally fixed to the muscularis mucosae, instead of being relatively mobile within the submucosal strata, thereby causing abnormal stresses as the tissues move during normal peristalsis. Dysplastic changes evidenced by subintimal fibrosis, loss of elastic fibers adjacent to the necrotic artery wall, and thinning or loss of circular fibers of the artery, which are seen at the point of rupture, support the theory that the final pathologic process VOLUME 58, NO. 2, 2003
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is one of slow weakening of the vessel wall with perhaps eventual localized dilation.5, s PATHOGENESlS
Dieulafoy's lesion is considered to be a congenital lesion, as it has been reported, albeit rarely, in neonates and young infants.9,1~ However, in most published series, there is a preponderance of men of advanced age.5,7,11,12 Comorbidities--particularly cardiovascular disease, hypertension, chronic renal failure, diabetes, and excessive use of alcohol have been described in almost 90% of the patients. 13 These factors suggest that perhaps the final rupture of the vessel results from the compound effects of the vascular ectasia, mucosal atrophy, and possible ischemic injury related to aging and cardiovascular diseases, which weaken an inherently vulnerable point. Despite a lack of direct evidence that the presentation of DL is caused by aspirin, coumadin, or nonsteroidal anti-inflammatory drugs, the use of these medications has been reported in more than 50% of patients.7,12-15 There is currently no evidence of any relationship between H e l i c o b a c t e r p y l o r i infection and DL. The phenomenon of GI hemorrhage from a blood vessel beneath a tiny mucosal defect similar to DL has been described in conditions in which there are "true" vascular pathologies. Pohle et al.16 described a case of fibromuscular dysplasia of the celiac axis arteries presenting as a fundal DL, and cases of GI pseudo-DL also have been described in both Beh~et's and Takayasu's vasculitis.17,18 Bleeding from an aortoesophageal fistula can also mimic a bleeding DL.19
Gastric anastomoses 5% Colon ~ Esophagus
Jejenu~leu~~(1%1% Duodenum 14%
mach 74%
A Gastdc s
Upper Stomach 65%
B D3
D1 53%
LOCATIONS OF DIEULAFOY'S LESION
A summary of the distribution of the sites where DL has been encountered, taken from case series published over the last decade, is shown in Figure 2A. In total, 249 cases were reported.11-13,2~ For 166 patients, the sites of the gastric DL can be identified, and the breakdown of the distribution in the stomach is shown in Figure 2B. It is of note that in two series, a high proportion of DL were found at intestinal anastomoses, predominantly Billroth II anastomoses after gastrectomy.11,21 In all published series, the proximal stomach is by far the most common site for DL. 7,11-14,20-23 The classic site is the proximal lesser curvature within 6 cm of the gastroesophageal junction and is the location in 64% to 82% of the cases.7,13 The predilection for the lesser curve may be related to the local blood supply; the lesser curve is one area of the stomach that is not perfused by a submucosal plexus but instead derives its blood supply directly from tributaries of the right and left gastric arteries. 24 VOLUME 58, NO. 2, 2003
DI/L junction C 18% Figure 2. Distribution of Dieulafoy's lesions in case series published since 1993. A, All sites (n = 249). B, Stomach (n = 166). C, Duodenum (n = 17).
The duodenum is the second most common site for DL, possibly because it also has a unique blood supply that often consists of end arteries. 25 Over half of the DL encountered in the duodenum occur in the bulb (Fig. 2C). 11-13,21,22,26,27 Dieulafoy's lesion occurred in segments of the small intestine distal to the ligament of Treitz in some 26 cases, most commonly the jejunum.13,15,21,28-31 GASTROINTESTINAL ENDOSCOPY
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Dieulafoy's lesion
Dieulafoy's lesion accounts for 1% to 5.8% of cases of acute nonvariceal upper GI bleeding.11-13,49 The two largest retrospective series, both from North America, found DL as the source of hemorrhage in 1.9% (90 DLs) and 1.2% (40 DLs) of all endoscopies performed for acute GI bleeding.13, 23 In the prospective study of Chung et al,, 4a DL was found in 3.4% of all patients with acute GI bleeding referred to their unit. The DL accounted for up to 40% of all causes of nonvariceal upper GI bleeding not caused by gastric or duodenal ulceration or esophageal varices in the prospective study of Matsui et el.50 In the study of Schmulewitz and BaiUie, 2a colonic DLs were only found in 0.09% of all colonoscopies performed for lower GI bleeding. The actual incidence of both upper and lower GI bleeding from DL is likely higher t h a n estimated because the diagnosis remains difficult. Figure 3. Endoscopic view of actively spurting Dieulafoy's lesion on lesser curve of stomach.
Colonic DL also is uncommon. It is most freq u e n t l y ~ound in t h e proximal colon and rectum.13,15,23, 32-35 Azimuddin et al. 36 described two cases of DL involving the anal canal. Esophageal DL is even rarer. The most common site is the distal esophagus, and DL has been found to be an alternative source of bleeding despite the presence of large varices. 13,37"39 Dieulafoy's lesion has been documented in children of all ages from the neonate upward, b u t it remains extremely rare in these age groups.9, lo As in the adult population, the stomach is the most common site in the pediatric age group, b u t DL has been described in the distal jejunum as well as the rectum. Dieulafoy's lesion in children appears to be amenable to the same endoscopic treatments as in adults.9,1o,40,41
Vascular lesions t h a t a p p e a r to fit the s a m e histopathologic description as DL have been described in the bronchus, where they present, as expected, as frank copious hemoptysis. 42-44 In two cases, there was a history of pulmonary tuberculosis.43, 44 "Caliber-persistent arteries" also have been found beneath cancerous ulcers on the lips.45, 46 PATIENT CHARACTERISTICS AND FREQUENCY OF DIEULAFOY'S LESION
Dieulafoy's lesion h a s a male predominance, being about twice as f r e q u e n t in men t h a n in women.7,1113,47, 48 Patients are usually in the range of 50 to 70 years old. 7,11,13,20 Significant comorbidities (28%-90%) are common and include cardiovascular and respiratory diseases; chronic renal failure is found in up to 30% of cases. 11,13,20,21,23 238
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PRESENTATION
Patients with DL usually have no history of dyspepsia or peptic ulcer disease. 15 Classic presentations include hematemesis alone (28%), hematemesis with melena (51%), and melena alone (18%). 7,14 Large volume hematochezia and shock can occur if bleeding is brisk. Based on data from recently published series, the mean n-tuber of units of blood transfused ranges from 3 to 8.11,13,20,21,48,51 From 44% to 77% of patients with DL had active bleeding at endoscopy (Fig. 3), whereas the remaining 23% to 56% had a visible vessel or a fresh adherent clot. 12,13,20 Bleeding from DL is often self-limiting, b u t life-threatening arterial bleeding occurs in about 10% of cases. DIAGNOSIS
Since the introduction of the flexible endoscope, the diagnosis of DL is frequently made at endoscopy i n s t e a d of surgery. P r o m p t EGD is essential for diagnosis, which m a y be difficult, as there is no ulcer base to indicate the source of bleeding. The diagnosis rates for initial endoscopy range from 49% to 92%.8,11-14,20,47, 49 Repeated endoscopic examination is frequently necessary because the bleeding point can be exceedingly small, bleeding can be intermittent, or the site m a y be covered b y a blood c10t.11,14,15,22,49, 52 Three or more endoscopic examinations have been required to make the diagnosis in u p to 6% of cases. 11"13,21 A t endoscopy, alternative pathologic conditions t h a t might give rise to h e m a t e m e s i s and melena are often encountered. Norton et el. la note significant erosions in 18% and peptic ulcers in 11% of their 90 DL cases. A similar r a t e of other "significant" endoscopic pathologies was found (17 of 40 cases) by Schmulewitz and Baillie. 23 The diagnosis of DL may be even more difficult in the presence of varices, especially gastric VOLUME 58, NO. 2, 2003
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varices. 16 For small bowel DL, push enteroscopy may improve diagnostic yield. 15 The commonly agreed endoscopic criteria for the diagnosis of DL are the following: (1) active arterial spurting or micropulsatile streaming of blood from a minute (<3 ram) mucosal defect or through normal surrounding mucosa; (2) visualization of a protruding vessel, with or without active bleeding, within a minute mucosal defect or through normal surrounding mucosa; or (3) fresh, densely adherent clot with a narrow point of attachment to a minute mucosal defect or to normal-appearing mucosa. 15 In difficult cases, angiography may be useful in making the diagnosis when endoscopy fails to identify the lesion, especially if the DL occurs in nongastric sites.14, 53 Angiographically, DL appears as a nontapering, convoluted, ectatic caliber-persistent artery at the bleeding site, with possible extravasation of blood.54,55 EUS may be useful in confirming the diagnosis of DL by detecting the aberrant vessel in the submucosa. 16,56"58 In one series of 8 patients with DL, relatively large-caliber (2-3 ram) vessels were clearly seen to penetrate the muscularis propria. 56 By using pulsed and color Doppler US, it is now possible to delineate precisely the location, type of vessel, depth, and configuration of the DL.16,57-59 EUS also is helpful in differentiating DL from gastric varices. EUSguided treatment of the underlying vessel also is possible.56,58,59 Furthermore, Doppler EUS can confirm ablation of a DL after injection therapy or elastic band ligation by documenting absence of blood flow.59,60
TREATMENT Multiple modalities and treatment methods for DL had been described, mostly in small case series and nonrandomized studies because of the rarity of the disease.
Endoscopic treatment Hemostasis can be achieved by endoscopic treatment in more than 90% of patients.ILl2,49,61, 62 Endoscopic therapy can be divided into injection o r thermal probe monotherapy or combination therapy. Monotherapy. Injection monotherapy using epinephrine, 63 a sclerosant,13, 49 alcohol,20,61 cyanoacrylate g l u e , 64 and hypertonic glucose solution 16 has been reported. The initial hemostasis rate of injection therapy may be as high a s 95%.49,61, 63 However, the rate of recurrent bleeding after injection monotherapy is reported to be relatively high (up to 55%)1L 12 and gastric perforation has been documented after sclerotherapy.13,65 Between 1984 and 1991, Baettig et al. 11 treated 19 patients with actively bleeding DL with injection VOLUME 58, NO. 2, 2003
therapy using epinephrine or polidocanol. The endoscopic treatment was "successful" after one session in 15 cases; two patients required a second treatment session, and one required a third. One patient required an emergency operation because of uncontrolled bleeding. Thermal probe monotherapy (monopolar or bipolar electrocoagulation, heat probe coagulation) appears to be as effective as single injection monotherapy. In the largest case series, Norton et al.13 achieved hemostasis in 79% of their 90 patients. Heat probe therapy was applied in 71 of these cases, although it was not entirely clear that this was applied without prior injection therapy in all cases. 13 In a much smaller series, Lin et al.52 reported 100% success in 6 patients treated by heat probe coagulation alone. Parra-Blanco et al., 2~ however, had a slightly lower success rate; two of 6 patients initially treated with heat probe monotherapy had recurrent bleeding. In one, the bleeding was controlled by hemoclip application and, in the other, by ethanol injection followed by hemoclip placement. The Nd:YAG laser has also been used to treat DL.15,62,66 Skok 62 treated 5 patients with Nd:YAG laser photocoagulation, achieving hemostasis in 4. One patient required re-treatment with hemostasis achieved long term. All patients survived. Combination therapy. Combination therapy with injection followed by thermal probe coagulation does, however, seem to offer more secure hemostasis by comparison w i t h monotherapy. Stark et al. 63 treated 19 patients with sclerotherapy followed by heat probe coagulation, bipolar coagulation, and Nd:YAG laser photocoagulation, with a hemostasis rate of 95% (18/19). An extensive review of 40 patients treated over a 6-year period at a major tertiary referral center found that the overall rate of successful hemostasis was 90%. 23 Of the 28 patients treated by using combined epinephrine injection and heat probe therapy, two eventually required surgical intervention. Only one in 24 patients had recurrent bleeding from DL at a median follow up of 15 months. Kasapidis et al. 12 retrospectively compared the short- and long-term results of injection therapy (epinephrine or sclerotherapy with ethanolamine oleate) with thermal coagulation, either alone or in combination with epinephrine injection, in the treatment of DL. Eighteen patients with DL were identified among 1750 (1%) who presented with acute, nonvariceal upper GI hemorrhage over an 8year period. Of 9 patients treated with injection therapy, 5 had recurrent bleeding; in contrast, no patient had recurrent bleeding among a further 9 who were treated with heat probe therapy (one GASTROINTESTINAL ENDOSCOPY 2 3 9
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patient), or heat probe combined with epinephrine injection (8 patients). In 4 of the 5 patients with recurrent hemorrhage, the bleeding could be controlled with further endoscopic therapy, resulting in a permanent hemostasis rate of 94%. 12
Mechanical hemostasis methods Band ligation. Endoscopic elastic band ligation (EBL), as designed for treatment ofvarices, has been used to treat DL with notable success. Reported hemostasis rates range from 75% to 100%.21, 50,67-69 In a prospective study of therapeutic options for nonvariceal upper GI hemorrhage, Matsui et al. 50 treated 27 patients with DL. Hemostasis was achieved in 100% (13/13) of patients treated with EBL, as compared with 85.7% (12/14) of those treated with bipolar electrocoagulation.50 Nikolaidis et al.21 retrospectively reviewed the results of EBL in 23 patients with DL. Endoscopic elastic band ligation was used as a rescue therapy in 4 patients and as the initial treatment in 19. Hemostasis was achieved in 22 of the 23 patients (96%); one patient had a jejunal DL and recurrent bleeding that required surgery. Sixteen (70%) patients required one band; two were used in 6 patients. At a median follow-up of 18 months, there was no recurrent hemorrhage from a DL. 21 Endoscopic-elastic band ligation has been used successfully to treat not only gastric DL but also DL in the esophagus, 3s duodenum,67,70 jejunum, 71 and r e c t u m . 72 Endoscopic elastic band ligation also may have additional advantage in patients with severe coagulopathies.2L 73 One patient is described in whom bleeding recurred 6 days after initial therapy because of a banding-induced ulcer, but this did not require further intervention. 21 Hemoclip. Hachisu 74 in 1988 was the first to report successful treatment of a gastric DL by hemoclip application. In the first ever prospective study of therapies for DL, Chung et al. 48 randomized 24 patients to receive either hypertonic saline-epinephrine solution injection or a mechanical method consisting of either hemoclip placement or EBL. Endoscopic mechanical therapy generally was shown to be more effective than the injection method in terms of the rates of initial hemostasis (91.7% vs. 75%), recurrent bleeding (8.3% vs. 33.3%; p = 0.033), permanent hemostasis (100% vs. 83.3%), and the need for surgery (0% vs. 17%). There was a statistically nonsignificant difference in the number of therapeutic endoscopic sessions needed to achieve hemostasis (1.17 for the mechanical treatment vs. 1.67 for injection treatment group). Mechanical treatment was shown to have a particularly good success rate for proximal gastric lesions and those found to have a protruding vessel or active bleeding. 48 240
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Parra-Blanco et al.20 used hemoclip placement to control hemorrhage from DL in 69% of their cases. Hemoclip therapy was successful in 94% (17 of 18 patients), the mean number of clips applied being 2.7. In addition, the hemoclip was used as salvage therapy in two patients in whom other treatments (ethanol injection and heat probe therapy) were unsuccessful. Hemoclip application also has been effective in controlling colonic DL hemorrhage. 75
Adjuvant therapy There are little data as to whether acid suppressive therapy is required after endoscopic therapy, but, in view of the relatively high frequency of concurrent GI pathology, this might seem logical. Proton pump inhibitors (both intravenous and orally administered), H2 receptor antagonists, and sucralfate have been given routinely in some centers.ll,12,21,50
Angiography Angiography can be used not only to localize a DL but to stop the bleeding by selective embolization of the feeding vessel, thereby, avoiding surgery.14, 55 In a review of 177 DL reported in publications to 1991, 11 patients underwent angiography for localization of the lesion and 4 had gel-foam embolization. 14 Three of the 4 patients had no further bleeding. However, results were disappointing in another series of 3 patients who had selective embolization of a DL; all patients required surgical intervention.23
Surgery Surgery has become the last resort for patients with uncontrolled bleeding from DL or an unidentified bleeding site. Despite the high success rate of endoscopic t r e a t m e n t , salvage surgery was still required in 3% to 16% of patients in published series.11-15,20,23,48, 62 Intraoperative enteroscopy may be needed to localize the bleeding site. Surgical oversewing of the vessel is associated with a higher risk of recurrent bleeding, and wedge resection of the involved gut segment may be a better surgical procedure in these patients with refractory bleeding.7,14 Wide gastrotomy is recommended to allow removal of clots and a clear view of the gastric mucosa. 76 If the bleeding point is not evident, wiping the mucosa with a dry gauze may precipitate hemorrhage and reveal the lesion. 77 Careful palpation of the stomach between finger and thumb, feeling for the thickened blood vessels and clot, can sometimes reveal the DL. 78 A vagotomy is not necessary.14, 77 "Blind" resection or subtotal gastrectomy is not recommended because the lesion may not be included in the resected part and massive VOLUME 58, NO. 2, 2003
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recurrent bleeding has occurred after surgery. 14 The reported mortality rate after surgery remains high, up to 33%. 14 RECURRENT BLEEDING Short-torm, recurrent bleeding is common, occurring in 6% to 28% of cases.14,15,20, 49,62 In series in which rates of recurrent bleeding at 72 hours could be compared, mechanical (EBL or hemoclip) or combined injection with coagulation appear bettor than injection monotherapy.12,50, 51 In a study of experience at one center, single-modality therapy had a higher rate of recurrent bleeding (up to 50%). 79 Repeated endoscopic treatment is recommended as hemostasis can be achieved in almost all patients. 14 Because the lesion is small and may not be found easily after the initial endoscopy, tattooing of the site is advocated to facilitate future endoscopic or surgical localization.12,80, 81 Long term, rates of recurrence and recurrent bleeding appear low once the DL is completely treated. In two studies, during a m e a n follow-up of 3 years after endoscopic treatment of DLs, there was no recurrence of bleeding.12, 2~ MORTALITY Before the era of endoscopic therapy, patients o i ~ n required surgery and the mortality rate was as high as 80%. 2 In the most recent series, mortality rates were significantly below 20%.11,13,14,20,23,47,49,62,66 Mortality after intervention was found to be associated with either advanced age or pre-existing systemic diseases and not directly from continued GI bleeding. CONCLUSION In conclusion, DL is an uncommon disorder, but the associated brisk hemorrhage leads to a relatively high morbidity. Prompt endoscopic examination and possibly multiple repeated endoscopies may be needed to make the diagnosis. Endoscopic treatment can achieve hemostasis in greater than 90% of cases. Multimodality therapy has been shown to be more effective than single modality in preventing recurrent bleeding, and mechanical therapies, including EBL and hemoclip application, have been demonstrated to be at least as effective in achieving hemostasis and preventing further bleeding. Surgical treatment remains the last resort. With the improvements in treatment armamentarium, the mortality related to DL has significantly decreased. REFERENCES 1. Mallory T. Cirsoid aneurysm of the left gastric artery. N Engl J Med 1946;235:524-7. 2. Goldman R. Submucosal arterial malformation (aneurysm) of VOLUME 58, NO. 2, 2003
the stomach with fatal hemorrhage. Gastroenterology 1964; 46:589-94. 3. Gallard T. Aneurysmes miliaires de l'estomac dormant lieu des h~mat~m~ses mortelles [French]. Bull soc m~d de hSp Paris 1884;1:84-91. 4. Dieulafoy G. Exulceratio simplex. Clin m6d de r HStel-Dieu de Paris 1897/98, II; L'intervention chirurgicale dans lee h~mat~m~ses foudroyantes cons~cutives ~il'exulceration simple de restomac [French]. Pr m6d 1898;29-44. 5. Miko TL, Thomazy VA. The caliber persistent artery of the stomach: a unifying approach to gastric aneurysm, Dieulafoy's lesion, and submucosal arterial malformation. Hum Pathol 1988;19:914-21. 6. Molnar P, Miko T. Multiple arterial caliber persistence resulting in hematomas and fatal rupture of the gastric wall. Am J Surg Pathol 1982;6:83-6. 7. Veldhuyzen van Zanten SJ, Bartelsman JF, Schipper ME, Tytgat GN. Recurrent massive haematemesis from Dieulafoy vascular malformations: a review of 101 cases. Gut 1986;27: 213-22. 8. Juler GL, Labitzke HG, Lamb R, Allen R. The pathogenesis of Dieulafoy's gastric erosion. Am J Gastroenterol 1984;79:195200. 9. Stockwell JA, Weruer HA, Marsano LS. Dieulafoy's lesion in an infant: a rare cause of massive gastrointestinal bleeding. J Pediatr Gastroenterol Nutr 2000;31:68-70. 10. Lee YJ, Oh JM, Park SE, Park JH. Successful treatment of a gastric Dieulafoy's lesion with a hemoclip in a newborn infant. Gastrointest Endosc 2003;57:435-6. 11. Baettig B, Haecki W, Lammer F, Jost R. Dieulafoy's disease: endoscopic treatment and follow up. Gut 1993;34:1418-21. 12. Kasapidis P, Georgopoulos P, Delis V, Balatsos V, KonstantinidisA, Skandalis N. Endoscopic management and long-term follow-up of Dieulafoy's lesions in the upper GI tract. Gastrointest Endosc 2002;55:527-31. 13. Norton ID, Petersen BT, Sorbi D, Balm RK, Alexander GL, Gostout CJ. Management and long-term prognosis of Dieulafoy lesion. Gastrointest Endosc 1999;50:762-7. 14. Reilly HF 3rd, al-Kawas FH. Dieulafoy's lesion. Diagnosis and management. Dig Dis Sci 1991;36:1702-7. 15. Dy NM, Gostout CJ, Balm RK. Bleeding from the endoscopically-identified Dieulafoy lesion of the pro~mal small intestine and colon. Am J Gastroentorol 1995;90:108-11. 16. Pohle T, Helleberg M, Menzel J, Diallo R, Vestring T, Senninger N, et al. An extraordinary Dieulafoy's lesion presenting as varices of the gastric fundus. Gastrointest Endosc 2001;54:776-9. 17. Arendt T, Kloehn S, Bastian A, Bewig B, Lins M, Monig H, et al. A case of Beh~et's syndrome presenting with Dieulafoy's ulcer. Z Gastroenterol 1997;35:935-8. 18. Usui J, Takemura H, Yuhara T, Akama T, Suzuki H, Yamane K, et al. Dieulafoy's lesion of the esophagus as a probable complication of Takayasu's arteritis. J Rheumatol 1999;26:454-6. 19. Lee OJ, Kim SH. Aortoesophageal fistula associated with tuberculous mediastinitis, mimicking esophageal Dieulafoy's disease. J Korean Med Sci 2002;17:266-9. 20. Parra-Blanco A, Takahashi H, Mendez Jerez PV, Kojima T, Aksoz K, Kirihara K, et al. Endoscopic management of Dieulafoy lesions of the stomach: a case study of 26 patients. Endoscopy 1997;29:834-9. 21. Nikolaidis N, Zezos P, Giouleme O, Budas K, Marakis G, Paroutoglou G, et al. Endoscopic band ligation of Dieulafoylike lesions in the upper gastrointestinal tract. Endoscopy 2001;33:754-60. 22. Chung YF, Wong WK, Soo KC. Diagnostic failures in endosGASTROINTESTINAL ENDOSCOPY
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44. Hope-GiU B, Prathibha BV. Bronchoscopic and angiographic findings in Dieulafoy's disease of the bronchus. Hosp Med 2002;63:178-9. 45. Miko T, Adler P, Endes P. Simulated cancer of the lower lip attributed to a "caliber persistent" artery. J Oral Pathol 1980;9:137-44. 46. Marshall RJ, Leppard BJ. Ulceration of the lip associated with a 'calibre-persistent artery'. Br J Dermatel 1985;113: 757-60. 47. Katz PO, Salas L. Less frequent causes of upper gastrointestinal bleeding. Gastroenterol Clin North Am 1993;22:875-89. 48. Chung IK, Kim EJ, Lee MS, Kim HS, Park SH, Lee MH, et al. Bleeding Dieulafoy's lesions and the choice of endoscopic method: comparing the hemostatic efficacy of mechanical and injection methods. Gastrointest Endosc 2000;52:721-4. 49. Pointner R, Schwab G, Konigsrainer A, Dietze O. Endoscopic treatment of Dieulafoy's disease. Gastroenterology 1988;94: 563-6. 50. Matsui S, Kamisako T, Kudo M, Inoue R. Endoscopic band ligation for control of nonvariceal upper GI hemorrhage: comparison with bipolar electrocoagulation. Gastrointest Endosc 2002;55:214-8. 51. Mumtaz R, Shaukat M, Ramirez FC. Outcomes of endoscopic treatment of gastroduodenal Dieulafoy's lesion with rubber band ligation and thermal/injection therapy. J Clin Gastroenterol 2003;36:310-4. 52. Lin HJ, Lee FY, Tsai YT, Lee SD, Lee CH, Kang WM. Therapeutic endoscopy for Dieulafoy's disease. J Clin Gastroenterol 1989;11:507-10. 53. Golding MI, Doman DB, Goldberg HJ. Dieulafoy's lesion treated by heater probe. Am J Gastroenterol 1990;85:1201-2. 54. Eidus LB, Rasuli P, Manion D, Heringer R. Caliber-persistent artery of the stomach (Dieulafoy's vascular malformation). Gastroenterology 1990;99:1507-10. 55. Durham JD, Kumpe DA, Rothbarth LJ, Van Stiegmann G. Dieulafoy disease: arteriographic findings and treatment. Radiology 1990;174:937-41. 56. Fockens P, Meenan J, van Dullemen HM, Bolwerk CJ, Tytgat GN. Dieulafoy's disease: endosonographic detection and endosonography-guided treatment. Gastrointest Endosc 1996;44:437-42. 57. Nesje LB, Skarstein A, Matre K, Myking AO, Odegaard S. Dieulafoy's vascular malformation: role of endoscopic ultrasonography in therapeutic decision-muking. Scand J Gastroenterol 1998;33:104-8. 58. Ribeiro A, Vazquez-Sequeiros E, Wiersema MJ. Doppler EUSguided treatment of gastric Dieulafoy's lesion. Gastrointest Endosc 2001;53:807-9. 59. Jaspersen D. Dieulafoy's disease controlled by Doppler ultrasound endoscopic treatment. Gut 1993;34:857-8. 60. Folvik G, Nesje LB, Berstad A, Odegaard S. Endosonographyguided endoscopic band ligation of Dieulafoy's malformation: a case report. Endoscopy 2001;33:636-8. 61. Asaki S, Sate H, Nishimura T, Ohkubo S, Yamagata R, Ito S, et al. Endoscopic diagnosis and treatment of Dieulafoy's ulcer. Tohoku J Exp Med 1988;154:135-41. 62. Skok P. Endoscopic hemostasis in exulceratio simplexDieulafoy's disease hemorrhage: a review of 25 cases. Endoscopy 1998;30:590-4. 63. Stark ME, Gostout CJ, Balm RK. Clinical features and endoscopic management of Dieulafoy's disease. Gastrointest Endosc 1992;38:545-50. 64. D'Imperio N, Papadia C, Baroncini D, Piemontese A, Billi P, Dal Monte PP. N-butyl-2-cyanoacrylate in the endoscopic treatment of Dieulafoy ulcer. Endoscopy 1995;27:216. VOLUME 58, NO. 2, 2003
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65. Bedford RA, van Stolk R, Sivak MV, Chung RS, van Dam J. Gastric perforation ai~r endoscopic treatment of a Dieulafoy's lesion. Am J Gastroenterel. 1992;87:244-7. 66. A1-Kawas FH, O~eefe J. Nd:YAG laser treatment of a bleeding Dieulafoy's lesion. Gastrointest Endosc 1987;33:38-9. 67. Abi-Hanna D, Williams SJ, Gillespie PE, Bourke MJ. Endoscopic band ligation for non-variceal non-ulcer gastrointestinal hemorrhage. Gastrointest Endosc 1998;48:510-4. 68. Fallah MA, Fallah A. Bleeding Dieulafoy's lesion. Gastrointest Endosc 2002;56:115. 69. Wong RM, Ota S, Katoh A, Yamauchi A, Aral K, Kaneko K, et al. Endoscopic ligation for non-esophageal variceal upper gastrointestinal hemorrhage. Endoscopy 1998;30:774-7. 70. Hurlstone DP. Successful endoscopic band ligation of duodenal Dieulafoy's lesions. Further large controlled studies are required. Scand J Gastroenterol 2002;37:620. 71. Murray KF, Jennings RW, Fox VL. Endoscopic band ligation of a Dieulafoy lesion in the small intestine of a child. Gastrointest Endosc 1996;44:336-9. 72. Mizukami Y, Akahoshi K, Kondoh N, Harada N, Nawata H. Endoscopic band ligation for rectal Dieulafoy's lesion: serial endoscopic images. Endoscopy 2002;34:1032. 73. Tseng C, Burke S, Connors P, Green R, Carr-Locke DL.
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Endoscopic band ligation for treatment of non-variceal upper gastrointestinal bleeding. Endoscopy 1991;23:297-8. 74. Hachisu T. Evaluation of endoscopic hemostasis using an improved clipping apparatus. Surg Endosc 1988:22;13-7. 75. Sone Y, Nakano S, Takeda I, Kumada T, Kiriyama S, Hisanaga Y. Massive hemorrhage from a Dieulafoy lesion in the cecum: successful endoscopic management. Gastrointest Endosc 2000;51:510-2. 76. Strong RW. Dieulafoy's disease: a distinct clinical entity. Aust N Z J Surg 1984;54:337-9. 77. Mortensen NJ, Mountford RA, Davies JD, Jeans WD. Dieulafoy's disease: a distinctive arteriovenous malformation causing massive gastric haemorrhage. Br J Surg 1983;70:76-8. 78. Holten I, Tait N. Dieulafoy's ulcer: a palpable entity? Aust N Z J Surg 1992;62:815-7. 79. Savides TJ, Jeusen DM. Therapeutic endoscopy for nonvariceal gastrointestinal bleeding. Gastroenterol Clin North Am 2000;29:465-87. 80. Brown GR, Harford WV, Jones WF. Endoscopic band ligation of an actively bleeding Dieulafoy lesion. Gastrointest Endosc 1994;40:501-3. 81. Yarze JC. Routine endoscopic "marking" of Dieulafoy-like lesions. Am J Gastroenterol 2001;96:264-5.
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Dieulafoy's lesion (DL), also know as cirsoid aneurysm I and submucosal arterial malformation,2 was originally described by Gallard in 1884 and designated "exulceratio simplex" by the French surgeon Georges Dieulafoy 14 years later.3, 4 Dieulafoy believed that the lesion was the first stage of a gastric ulcer, the progression of which was interrupted by the occurrence of bleeding. Advances in endoscopic therapeutic methods have greatly decreased the associated mortality, but DL remains one of the most difficult diagnoses and somewhat of a pathologic puzzle.
PATHOLOGY Histologically, DL consists of an abnormal, submucosal "caliber-persistent artery" that typically protrudes through a minute 2- to 5-mm mucosal defect. The submucosal artery fails to undergo the usual ramification within the wall of the stomach or to diminish to the minute size of the mucosal capillary microvasculature.5,6 The diameter of the caliber-persistent artery at the muscularis mucosae level can range from 1 to 3 ram, almost 10 times the diameter of normal arteries at the same level (Fig. 1). 5,7 Histologically, there is subintimal fibrosis of the artery, but there is no true structural aneurysmal change. 5 Importantly, there is an absence of inflammation at the edge of the mucosal defect in contrast to that present in peptic ulcer disease. The tortuous arteries are accompanied by large veins, which Miko and Thomazy5 found to have led to both arterial and venous rupture in three fourths of the 24 pathology specimens examined. Intimal thickenCurrent affiliations: Departments of Medicine and Therapeutics, Prince of Wales Hospital, Chinese University of Hong Kong, Shatin, Hong Kong, Department of Gastroenterology, North Shore Hospital, Auckland, New Zealand. Dr. Walmsley is in receipt of a personal grant from the Genesis Oncology Trust, New Zealand. Reprint requests: Yuk Tong Lee, MD, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, N.T Hong Kong, China. Copyright 9 2003 by the American Society for Gastrointestinal Endoscopy 0016-5107/2003/$30.00 + 0 doi:l O.1067/ mge.2003.328 236
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Figure 1. Photomicrographof histologicsectionshowingcaliber persistentartery tracking through gastric submucosa (H&E, orig.mag.x 125). ing occurs in both veins and arteries with thrombosis formation, but the mechanism of final rupture of the vessel is uncertain.5,8 The very first case description of this phenomenon was that of Gallard in 1884. Dieulafoy reported 3 of his own cases and identified 4 further cases in other publications. Dieulafoy found what he termed "miliary abscesses," which he believed perforated into the gastric lumen and exposed the normal blood vessels beneath to peptic digestion. He surmised this was the presentation of a nascent common type gastric ulcer and so coined the term "exulceratio simplex." Modem pathologists have proposed that bleeding occurs as a result of pressure erosion of the overlying epithelium by the ectatic vessel. 2 Miko and Thomazy5 suggested that these anomalous vessels are abnormally fixed to the muscularis mucosae, instead of being relatively mobile within the submucosal strata, thereby causing abnormal stresses as the tissues move during normal peristalsis. Dysplastic changes evidenced by subintimal fibrosis, loss of elastic fibers adjacent to the necrotic artery wall, and thinning or loss of circular fibers of the artery, which are seen at the point of rupture, support the theory that the final pathologic process VOLUME 58, NO. 2, 2003
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is one of slow weakening of the vessel wall with perhaps eventual localized dilation.5, s PATHOGENESlS
Dieulafoy's lesion is considered to be a congenital lesion, as it has been reported, albeit rarely, in neonates and young infants.9,1~ However, in most published series, there is a preponderance of men of advanced age.5,7,11,12 Comorbidities--particularly cardiovascular disease, hypertension, chronic renal failure, diabetes, and excessive use of alcohol have been described in almost 90% of the patients. 13 These factors suggest that perhaps the final rupture of the vessel results from the compound effects of the vascular ectasia, mucosal atrophy, and possible ischemic injury related to aging and cardiovascular diseases, which weaken an inherently vulnerable point. Despite a lack of direct evidence that the presentation of DL is caused by aspirin, coumadin, or nonsteroidal anti-inflammatory drugs, the use of these medications has been reported in more than 50% of patients.7,12-15 There is currently no evidence of any relationship between H e l i c o b a c t e r p y l o r i infection and DL. The phenomenon of GI hemorrhage from a blood vessel beneath a tiny mucosal defect similar to DL has been described in conditions in which there are "true" vascular pathologies. Pohle et al.16 described a case of fibromuscular dysplasia of the celiac axis arteries presenting as a fundal DL, and cases of GI pseudo-DL also have been described in both Beh~et's and Takayasu's vasculitis.17,18 Bleeding from an aortoesophageal fistula can also mimic a bleeding DL.19
Gastric anastomoses 5% Colon ~ Esophagus
Jejenu~leu~~(1%1% Duodenum 14%
mach 74%
A Gastdc s
Upper Stomach 65%
B D3
D1 53%
LOCATIONS OF DIEULAFOY'S LESION
A summary of the distribution of the sites where DL has been encountered, taken from case series published over the last decade, is shown in Figure 2A. In total, 249 cases were reported.11-13,2~ For 166 patients, the sites of the gastric DL can be identified, and the breakdown of the distribution in the stomach is shown in Figure 2B. It is of note that in two series, a high proportion of DL were found at intestinal anastomoses, predominantly Billroth II anastomoses after gastrectomy.11,21 In all published series, the proximal stomach is by far the most common site for DL. 7,11-14,20-23 The classic site is the proximal lesser curvature within 6 cm of the gastroesophageal junction and is the location in 64% to 82% of the cases.7,13 The predilection for the lesser curve may be related to the local blood supply; the lesser curve is one area of the stomach that is not perfused by a submucosal plexus but instead derives its blood supply directly from tributaries of the right and left gastric arteries. 24 VOLUME 58, NO. 2, 2003
DI/L junction C 18% Figure 2. Distribution of Dieulafoy's lesions in case series published since 1993. A, All sites (n = 249). B, Stomach (n = 166). C, Duodenum (n = 17).
The duodenum is the second most common site for DL, possibly because it also has a unique blood supply that often consists of end arteries. 25 Over half of the DL encountered in the duodenum occur in the bulb (Fig. 2C). 11-13,21,22,26,27 Dieulafoy's lesion occurred in segments of the small intestine distal to the ligament of Treitz in some 26 cases, most commonly the jejunum.13,15,21,28-31 GASTROINTESTINAL ENDOSCOPY
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Dieulafoy's lesion
Dieulafoy's lesion accounts for 1% to 5.8% of cases of acute nonvariceal upper GI bleeding.11-13,49 The two largest retrospective series, both from North America, found DL as the source of hemorrhage in 1.9% (90 DLs) and 1.2% (40 DLs) of all endoscopies performed for acute GI bleeding.13, 23 In the prospective study of Chung et al,, 4a DL was found in 3.4% of all patients with acute GI bleeding referred to their unit. The DL accounted for up to 40% of all causes of nonvariceal upper GI bleeding not caused by gastric or duodenal ulceration or esophageal varices in the prospective study of Matsui et el.50 In the study of Schmulewitz and BaiUie, 2a colonic DLs were only found in 0.09% of all colonoscopies performed for lower GI bleeding. The actual incidence of both upper and lower GI bleeding from DL is likely higher t h a n estimated because the diagnosis remains difficult. Figure 3. Endoscopic view of actively spurting Dieulafoy's lesion on lesser curve of stomach.
Colonic DL also is uncommon. It is most freq u e n t l y ~ound in t h e proximal colon and rectum.13,15,23, 32-35 Azimuddin et al. 36 described two cases of DL involving the anal canal. Esophageal DL is even rarer. The most common site is the distal esophagus, and DL has been found to be an alternative source of bleeding despite the presence of large varices. 13,37"39 Dieulafoy's lesion has been documented in children of all ages from the neonate upward, b u t it remains extremely rare in these age groups.9, lo As in the adult population, the stomach is the most common site in the pediatric age group, b u t DL has been described in the distal jejunum as well as the rectum. Dieulafoy's lesion in children appears to be amenable to the same endoscopic treatments as in adults.9,1o,40,41
Vascular lesions t h a t a p p e a r to fit the s a m e histopathologic description as DL have been described in the bronchus, where they present, as expected, as frank copious hemoptysis. 42-44 In two cases, there was a history of pulmonary tuberculosis.43, 44 "Caliber-persistent arteries" also have been found beneath cancerous ulcers on the lips.45, 46 PATIENT CHARACTERISTICS AND FREQUENCY OF DIEULAFOY'S LESION
Dieulafoy's lesion h a s a male predominance, being about twice as f r e q u e n t in men t h a n in women.7,1113,47, 48 Patients are usually in the range of 50 to 70 years old. 7,11,13,20 Significant comorbidities (28%-90%) are common and include cardiovascular and respiratory diseases; chronic renal failure is found in up to 30% of cases. 11,13,20,21,23 238
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PRESENTATION
Patients with DL usually have no history of dyspepsia or peptic ulcer disease. 15 Classic presentations include hematemesis alone (28%), hematemesis with melena (51%), and melena alone (18%). 7,14 Large volume hematochezia and shock can occur if bleeding is brisk. Based on data from recently published series, the mean n-tuber of units of blood transfused ranges from 3 to 8.11,13,20,21,48,51 From 44% to 77% of patients with DL had active bleeding at endoscopy (Fig. 3), whereas the remaining 23% to 56% had a visible vessel or a fresh adherent clot. 12,13,20 Bleeding from DL is often self-limiting, b u t life-threatening arterial bleeding occurs in about 10% of cases. DIAGNOSIS
Since the introduction of the flexible endoscope, the diagnosis of DL is frequently made at endoscopy i n s t e a d of surgery. P r o m p t EGD is essential for diagnosis, which m a y be difficult, as there is no ulcer base to indicate the source of bleeding. The diagnosis rates for initial endoscopy range from 49% to 92%.8,11-14,20,47, 49 Repeated endoscopic examination is frequently necessary because the bleeding point can be exceedingly small, bleeding can be intermittent, or the site m a y be covered b y a blood c10t.11,14,15,22,49, 52 Three or more endoscopic examinations have been required to make the diagnosis in u p to 6% of cases. 11"13,21 A t endoscopy, alternative pathologic conditions t h a t might give rise to h e m a t e m e s i s and melena are often encountered. Norton et el. la note significant erosions in 18% and peptic ulcers in 11% of their 90 DL cases. A similar r a t e of other "significant" endoscopic pathologies was found (17 of 40 cases) by Schmulewitz and Baillie. 23 The diagnosis of DL may be even more difficult in the presence of varices, especially gastric VOLUME 58, NO. 2, 2003
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varices. 16 For small bowel DL, push enteroscopy may improve diagnostic yield. 15 The commonly agreed endoscopic criteria for the diagnosis of DL are the following: (1) active arterial spurting or micropulsatile streaming of blood from a minute (<3 ram) mucosal defect or through normal surrounding mucosa; (2) visualization of a protruding vessel, with or without active bleeding, within a minute mucosal defect or through normal surrounding mucosa; or (3) fresh, densely adherent clot with a narrow point of attachment to a minute mucosal defect or to normal-appearing mucosa. 15 In difficult cases, angiography may be useful in making the diagnosis when endoscopy fails to identify the lesion, especially if the DL occurs in nongastric sites.14, 53 Angiographically, DL appears as a nontapering, convoluted, ectatic caliber-persistent artery at the bleeding site, with possible extravasation of blood.54,55 EUS may be useful in confirming the diagnosis of DL by detecting the aberrant vessel in the submucosa. 16,56"58 In one series of 8 patients with DL, relatively large-caliber (2-3 ram) vessels were clearly seen to penetrate the muscularis propria. 56 By using pulsed and color Doppler US, it is now possible to delineate precisely the location, type of vessel, depth, and configuration of the DL.16,57-59 EUS also is helpful in differentiating DL from gastric varices. EUSguided treatment of the underlying vessel also is possible.56,58,59 Furthermore, Doppler EUS can confirm ablation of a DL after injection therapy or elastic band ligation by documenting absence of blood flow.59,60
TREATMENT Multiple modalities and treatment methods for DL had been described, mostly in small case series and nonrandomized studies because of the rarity of the disease.
Endoscopic treatment Hemostasis can be achieved by endoscopic treatment in more than 90% of patients.ILl2,49,61, 62 Endoscopic therapy can be divided into injection o r thermal probe monotherapy or combination therapy. Monotherapy. Injection monotherapy using epinephrine, 63 a sclerosant,13, 49 alcohol,20,61 cyanoacrylate g l u e , 64 and hypertonic glucose solution 16 has been reported. The initial hemostasis rate of injection therapy may be as high a s 95%.49,61, 63 However, the rate of recurrent bleeding after injection monotherapy is reported to be relatively high (up to 55%)1L 12 and gastric perforation has been documented after sclerotherapy.13,65 Between 1984 and 1991, Baettig et al. 11 treated 19 patients with actively bleeding DL with injection VOLUME 58, NO. 2, 2003
therapy using epinephrine or polidocanol. The endoscopic treatment was "successful" after one session in 15 cases; two patients required a second treatment session, and one required a third. One patient required an emergency operation because of uncontrolled bleeding. Thermal probe monotherapy (monopolar or bipolar electrocoagulation, heat probe coagulation) appears to be as effective as single injection monotherapy. In the largest case series, Norton et al.13 achieved hemostasis in 79% of their 90 patients. Heat probe therapy was applied in 71 of these cases, although it was not entirely clear that this was applied without prior injection therapy in all cases. 13 In a much smaller series, Lin et al.52 reported 100% success in 6 patients treated by heat probe coagulation alone. Parra-Blanco et al., 2~ however, had a slightly lower success rate; two of 6 patients initially treated with heat probe monotherapy had recurrent bleeding. In one, the bleeding was controlled by hemoclip application and, in the other, by ethanol injection followed by hemoclip placement. The Nd:YAG laser has also been used to treat DL.15,62,66 Skok 62 treated 5 patients with Nd:YAG laser photocoagulation, achieving hemostasis in 4. One patient required re-treatment with hemostasis achieved long term. All patients survived. Combination therapy. Combination therapy with injection followed by thermal probe coagulation does, however, seem to offer more secure hemostasis by comparison w i t h monotherapy. Stark et al. 63 treated 19 patients with sclerotherapy followed by heat probe coagulation, bipolar coagulation, and Nd:YAG laser photocoagulation, with a hemostasis rate of 95% (18/19). An extensive review of 40 patients treated over a 6-year period at a major tertiary referral center found that the overall rate of successful hemostasis was 90%. 23 Of the 28 patients treated by using combined epinephrine injection and heat probe therapy, two eventually required surgical intervention. Only one in 24 patients had recurrent bleeding from DL at a median follow up of 15 months. Kasapidis et al. 12 retrospectively compared the short- and long-term results of injection therapy (epinephrine or sclerotherapy with ethanolamine oleate) with thermal coagulation, either alone or in combination with epinephrine injection, in the treatment of DL. Eighteen patients with DL were identified among 1750 (1%) who presented with acute, nonvariceal upper GI hemorrhage over an 8year period. Of 9 patients treated with injection therapy, 5 had recurrent bleeding; in contrast, no patient had recurrent bleeding among a further 9 who were treated with heat probe therapy (one GASTROINTESTINAL ENDOSCOPY 2 3 9
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patient), or heat probe combined with epinephrine injection (8 patients). In 4 of the 5 patients with recurrent hemorrhage, the bleeding could be controlled with further endoscopic therapy, resulting in a permanent hemostasis rate of 94%. 12
Mechanical hemostasis methods Band ligation. Endoscopic elastic band ligation (EBL), as designed for treatment ofvarices, has been used to treat DL with notable success. Reported hemostasis rates range from 75% to 100%.21, 50,67-69 In a prospective study of therapeutic options for nonvariceal upper GI hemorrhage, Matsui et al. 50 treated 27 patients with DL. Hemostasis was achieved in 100% (13/13) of patients treated with EBL, as compared with 85.7% (12/14) of those treated with bipolar electrocoagulation.50 Nikolaidis et al.21 retrospectively reviewed the results of EBL in 23 patients with DL. Endoscopic elastic band ligation was used as a rescue therapy in 4 patients and as the initial treatment in 19. Hemostasis was achieved in 22 of the 23 patients (96%); one patient had a jejunal DL and recurrent bleeding that required surgery. Sixteen (70%) patients required one band; two were used in 6 patients. At a median follow-up of 18 months, there was no recurrent hemorrhage from a DL. 21 Endoscopic-elastic band ligation has been used successfully to treat not only gastric DL but also DL in the esophagus, 3s duodenum,67,70 jejunum, 71 and r e c t u m . 72 Endoscopic elastic band ligation also may have additional advantage in patients with severe coagulopathies.2L 73 One patient is described in whom bleeding recurred 6 days after initial therapy because of a banding-induced ulcer, but this did not require further intervention. 21 Hemoclip. Hachisu 74 in 1988 was the first to report successful treatment of a gastric DL by hemoclip application. In the first ever prospective study of therapies for DL, Chung et al. 48 randomized 24 patients to receive either hypertonic saline-epinephrine solution injection or a mechanical method consisting of either hemoclip placement or EBL. Endoscopic mechanical therapy generally was shown to be more effective than the injection method in terms of the rates of initial hemostasis (91.7% vs. 75%), recurrent bleeding (8.3% vs. 33.3%; p = 0.033), permanent hemostasis (100% vs. 83.3%), and the need for surgery (0% vs. 17%). There was a statistically nonsignificant difference in the number of therapeutic endoscopic sessions needed to achieve hemostasis (1.17 for the mechanical treatment vs. 1.67 for injection treatment group). Mechanical treatment was shown to have a particularly good success rate for proximal gastric lesions and those found to have a protruding vessel or active bleeding. 48 240
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Parra-Blanco et al.20 used hemoclip placement to control hemorrhage from DL in 69% of their cases. Hemoclip therapy was successful in 94% (17 of 18 patients), the mean number of clips applied being 2.7. In addition, the hemoclip was used as salvage therapy in two patients in whom other treatments (ethanol injection and heat probe therapy) were unsuccessful. Hemoclip application also has been effective in controlling colonic DL hemorrhage. 75
Adjuvant therapy There are little data as to whether acid suppressive therapy is required after endoscopic therapy, but, in view of the relatively high frequency of concurrent GI pathology, this might seem logical. Proton pump inhibitors (both intravenous and orally administered), H2 receptor antagonists, and sucralfate have been given routinely in some centers.ll,12,21,50
Angiography Angiography can be used not only to localize a DL but to stop the bleeding by selective embolization of the feeding vessel, thereby, avoiding surgery.14, 55 In a review of 177 DL reported in publications to 1991, 11 patients underwent angiography for localization of the lesion and 4 had gel-foam embolization. 14 Three of the 4 patients had no further bleeding. However, results were disappointing in another series of 3 patients who had selective embolization of a DL; all patients required surgical intervention.23
Surgery Surgery has become the last resort for patients with uncontrolled bleeding from DL or an unidentified bleeding site. Despite the high success rate of endoscopic t r e a t m e n t , salvage surgery was still required in 3% to 16% of patients in published series.11-15,20,23,48, 62 Intraoperative enteroscopy may be needed to localize the bleeding site. Surgical oversewing of the vessel is associated with a higher risk of recurrent bleeding, and wedge resection of the involved gut segment may be a better surgical procedure in these patients with refractory bleeding.7,14 Wide gastrotomy is recommended to allow removal of clots and a clear view of the gastric mucosa. 76 If the bleeding point is not evident, wiping the mucosa with a dry gauze may precipitate hemorrhage and reveal the lesion. 77 Careful palpation of the stomach between finger and thumb, feeling for the thickened blood vessels and clot, can sometimes reveal the DL. 78 A vagotomy is not necessary.14, 77 "Blind" resection or subtotal gastrectomy is not recommended because the lesion may not be included in the resected part and massive VOLUME 58, NO. 2, 2003
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recurrent bleeding has occurred after surgery. 14 The reported mortality rate after surgery remains high, up to 33%. 14 RECURRENT BLEEDING Short-torm, recurrent bleeding is common, occurring in 6% to 28% of cases.14,15,20, 49,62 In series in which rates of recurrent bleeding at 72 hours could be compared, mechanical (EBL or hemoclip) or combined injection with coagulation appear bettor than injection monotherapy.12,50, 51 In a study of experience at one center, single-modality therapy had a higher rate of recurrent bleeding (up to 50%). 79 Repeated endoscopic treatment is recommended as hemostasis can be achieved in almost all patients. 14 Because the lesion is small and may not be found easily after the initial endoscopy, tattooing of the site is advocated to facilitate future endoscopic or surgical localization.12,80, 81 Long term, rates of recurrence and recurrent bleeding appear low once the DL is completely treated. In two studies, during a m e a n follow-up of 3 years after endoscopic treatment of DLs, there was no recurrence of bleeding.12, 2~ MORTALITY Before the era of endoscopic therapy, patients o i ~ n required surgery and the mortality rate was as high as 80%. 2 In the most recent series, mortality rates were significantly below 20%.11,13,14,20,23,47,49,62,66 Mortality after intervention was found to be associated with either advanced age or pre-existing systemic diseases and not directly from continued GI bleeding. CONCLUSION In conclusion, DL is an uncommon disorder, but the associated brisk hemorrhage leads to a relatively high morbidity. Prompt endoscopic examination and possibly multiple repeated endoscopies may be needed to make the diagnosis. Endoscopic treatment can achieve hemostasis in greater than 90% of cases. Multimodality therapy has been shown to be more effective than single modality in preventing recurrent bleeding, and mechanical therapies, including EBL and hemoclip application, have been demonstrated to be at least as effective in achieving hemostasis and preventing further bleeding. Surgical treatment remains the last resort. With the improvements in treatment armamentarium, the mortality related to DL has significantly decreased. REFERENCES 1. Mallory T. Cirsoid aneurysm of the left gastric artery. N Engl J Med 1946;235:524-7. 2. Goldman R. Submucosal arterial malformation (aneurysm) of VOLUME 58, NO. 2, 2003
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