CLINICAL REVIEW
The Dieulafoy’s Lesion An Update on Evaluation, Diagnosis, and Management David C. Nguyen, MD* and Christian S. Jackson, MD, FACGw
Abstract: Dieulafoy’s lesion (DL) is a persistently wide caliber artery that is observed more frequently at the fifth decade of life in the male population with multiple comorbidities. There are a variety of endoscopic therapies that have been used to treat DL; however, there are no clear guidelines on the best treatment modality. This article systematically reviews the diagnosis, the most commonly reported therapies of DL, and offers a suggested algorithm based upon efficacy of treatment such as initial hemostasis, rebleeding rates, and mortality. Key Words: Dieulafoy’s lesion, upper and lower gastrointestinal bleeding, hemoclips, band ligation, heater probe, bipolar electrocoagulation, local epinephrine injection, argon plasma coagulation, N-butyl-2-cyanoacrylate
(J Clin Gastroenterol 2015;49:541–549)
D
ieulafoy’s lesion (DL) is an uncommon, but potentially life-threatening condition, which can result in sudden, massive gastrointestinal (GI) bleeding. This lesion was described as early as 1884 by Gallard who reported 2 autopsy cases from massive upper GI bleed secondary to “miliary aneurysms of the stomach.” In 1897, Georges Dieulafoy thought that he observed a precursor lesion that bled before it had a chance to develop into a gastric ulcer; thus, calling it “exulceratio simplex.”1,2 Since these initial observations, DL has been diagnosed throughout the GI tract including extragastric locations such as the esophagus, small bowel, and colon.3–7 DL has been referred to as a caliber persistent artery, cirsoid aneurysm, and submucosal arterial malformation.1,3–5,8–11 As endoscopic technology, operator skill and clinician awareness have improved, mortality associated with DL has decreased. However, it still remains a diagnostic and therapeutic challenge. We performed a systematic review of the most current understanding of the pathogenesis, possible risk factors, prognosis, diagnostic modalities of DL. In addition, we evaluated and compiled the initial hemostasis and rebleeding rates for current endoscopic management modalities of DL.
From the *VA Loma Linda Health Care System; and wLoma Linda University and VA Loma Linda Health Care System, Loma Linda, CA. The authors declare that they have nothing to disclose. Reprints: David C. Nguyen, MD, VA Loma Linda Health Care System, 11201 Benton Street, Loma Linda, CA 92357 (e-mail: davidngn@ gmail.com) and Christian S. Jackson, MD, FACG, Loma Linda University and VA Loma Linda Health Care System, 11201 Benton Street, Loma Linda, CA 92357 (e-mail: [email protected]). Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
J Clin Gastroenterol
Volume 49, Number 7, August 2015
MATERIALS AND METHODS Using PubMed we searched for papers by using the following terms: Dieulafoy’s lesion, Dieulafoy lesion, diagnosis, treatment and the reference lists of relevant articles from January 1, 1978 to January 12, 2015. Papers that we included met endoscopic criteria for DL or biopsyproven diagnosis; described location, treatment, initial hemostasis rates, rebleed rates, mortality, and follow-up. The reasons for exclusion are non-English papers, pediatric DL, and lack of sufficient information pertaining to DL.
PATHOLOGY The predominant characteristic of DL is a persistently, large caliber artery, 1 to 3 mm in size, that runs a tortuous path through the submucosa with variable length, protruding through a mucosal defect of 2 to 5 mm.1,2,12 Juler et al2 showed that the surrounding mucosa around DL was histologically normal, lacking findings of ulceration. This artery does not undergo embedding within the wall of the stomach.1,2,10,12,13 The artery has a thick subintimal fibrosis, but no findings of aneurysm, atherosclerosis, or vasculitis.1,2,12 These histologic findings are consistent throughout the GI tract and extraintestinal locations.7,14–18 Miko´ and Thoma´zy12 determined that the average DL measured 1.08 mm in diameter, approximately 10 times the size of a normal artery at a similar mucosa level in the stomach. Submucosal arteries in the lesser curvature arise directly from the left gastric artery as opposed to arising from a plexus of submucosal arteries.1,2 However, there is no similar anatomic explanation elsewhere in the GI tract.
PATHOGENESIS The mechanism of DL’s rupture is unclear. One theory suggests that the path of a DL runs in close proximity to the overlying mucosa; thus, DL’s pulsations may disrupt this epithelium, leading to localized ischemia, erosion of the mucosa, and rupture of the artery.3,12 Another theory proposes that the long-term gastric mechanical forces may bring about the formation of intravascular thrombi, leading to disruption of the vessel wall.2 Stercoral effects of bowel contents may play the initiating factor to the development of mucosal erosion in the lower GI tract.19 Risk factors that have been proposed to bring about the rupture of DL, but have not been connected to DL are comorbidities such as cardiovascular disease or diabetes mellitus, the use of nonsteroidal anti-inflammatory drugs (NSAIDS), aspirin (ASA), warfarin, clopidogrel, steroids, and alcohol.1,20–31 Norton et al20 noted that 51% of their patients took either aspirin or NSAIDs, but the mucosa around the DL was normal. The use of these medications may either play a minor role in the development of bleeding www.jcge.com |
Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
541
J Clin Gastroenterol
Nguyen and Jackson
in DL or more likely a byproduct of patients’ vascular disease.21 To date there has not been large population studies looking at predilection of DL with regard to race, ethnicity or socioeconomic status. Furthermore, no evidence suggests a connection between H. pylori infection and DL.
INCIDENCE The incidence ranges from 0.1% to 5.8% of all nonvariceal upper GI bleeds and for all GI bleeds the incidence is between 0.09% and 1.55%.21,23,28,31–37 Dulic-Lakovic et al’s38 retrospective study noted that small bowel DL accounted for approximately 3.5% of obscure GI bleeds. Schmulewitz and Baillie36 noted that colonic DL accounted for only 0.09% of all colonoscopies performed for lower GI bleeding. The incidence of DL may be difficult to determine due to the challenges of diagnosis.5,22,26,30,36,39–42 Table 1 summarizes the patient profile of the cases reviewed. Of note, DL can occur in pediatric age patients to patients as old as 90 years of age.128,129 Table 2 lists the most commonly reported diseases found in patients with DL. The percent of patients with at least 1 comorbidity can range from as low as 6% to as high as 90%.20,31 The number of patients with 2 or more comorbidities can be found as high as 83%.21 Cardiovascular disease, hypertension, and chronic kidney disease have been hypothesized to explain the weakened arterial vessel at the point of rupture, but some studies have suggested that these comorbidities may be more a product of age.36
CLINICAL MANIFESTATION Patients diagnosed with DL typically are men over 50 years of age with multiple comorbidities and present with an acute painless, massive GI bleeding. Table 3 describes symptoms and signs attributed to DL. The presentation of DL can range from iron deficiency anemia to life-threatening hemorrhagic shock.28,46 Hemodynamic shock can present as high as 87%.28,31,33,51,53,54
LOCATION The majority of DL will predominantly occur in the stomach (about 71% to 74%) with the duodenum as the second most common site (14% to 15%).4,5 It has been noted that 61% to 65% of DLs are found within 6 cm of the gastroesophageal junction.5,23 Within the duodenum, about half were located at the bulb.4,5 Colorectal DL makes up 5% of the established cases.4,5 Esophageal, jejunal, and ileal DL have been rarely reported.
DIAGNOSIS With the shift from surgical and pathologic confirmation of DL to endoscopic diagnoses, Dy et al34 suggested endoscopic criteria to diagnose DL (Fig. 1). The
Volume 49, Number 7, August 2015
TABLE 2. Most Commonly Reported Comorbidities (n = 832)20–24,26,27,33,37,55–58,65
Diseases
Percentage
Cardiovascular disease (coronary artery disease, chronic heart failure, valvular heart disease) Hypertension Chronic kidney disease Diabetes mellitus
33 24.7 11.8 8.2
term “Dieulafoy-like lesion” signifies a lack of histologic evidence.34,110,115 The sensitivity of these criteria to diagnose DL has not been established. Early endoscopy may quickly identify this lesion while it is actively bleeding.5,20,27,37,54,128 Table 4 shows the bleeding characteristics of DL. DL is usually diagnosed on the first endoscopic attempt (Table 4), but in the remaining 20% require a second attempt to diagnose DL. Therapeutic endoscopes with increased suctioning capabilities or shifting the patient’s position during endoscopy to move the intragastric blood can aid diagnosis.34,58 In addition, one can consider using erythromycin or metoclopramide 20 to 120 minutes before upper endoscopy in patients who are highly likely to have fresh blood or clots in the stomach as this will decrease the need to repeat upper endoscopy.130,131 Angiography has been used in cases where endoscopy has failed to identify the cause of bleeding or if the patient is too unstable for endoscopy. It can also serve as a therapeutic option.5 Radiographically, DL will appear as a nontapering, tortuous artery with possible extravasation of blood.5,132 Endoscopic ultrasound (EUS) has been used to confirm the diagnosis of DL. Pulsed and color Doppler ultrasound has aided in the treatment of recurrent bleeds by confirming ablation of DL after injection therapy, band ligation, and hemoclip by documenting the absence of blood flow.25,80,109–111,113,114 In case reports, video capsule endoscopy (VCE) has identified DL in the small bowel, but when the patient is hemodynamically unstable VCE is a less viable of an option than deep enteroscopy.38,94,97,133 As such, VCE’s role in the diagnosis of DL is more appropriate in the setting of an obscure-overt GI bleeding. The advantage of using VCE over deep enteroscopy is that it is noninvasive and can determine the initial route of deep enteroscopy. There are 3 main limitations to VCE, inability to insufflate air, inability to clear the visual field, and lack of therapeutic capabilities.127,134 In practice, deep enteroscopy is the preferred technique of choice to treat hemodynamically unstable patients suspected of small bowel DL.38,97 Dulic-Lakovic et al38 demonstrated that an average of 1.5 attempts were needed to diagnose DL. The optimal route of deep enteroscopy (antegrade or retrograde) is dependent upon the clinician’s suspicion of the location of the bleeding source (proximal or distal) based on a complete VCE examination and
TABLE 1. Patient Characteristics7,13–127 Average age (y) (n = 1068) Sex (n = 1343) Comorbidities (at least 1 chronic condition) (n = 861) Medications (n = 842)
58.3 69% men, 31% women 62.7% 34.4% taking NSAIDs or antiplatelet, 5.3% warfarin
NSAID indicates nonsteroidal anti-inflammatory drugs.
TABLE 3. Symptoms (n = 689)7,14–17,19–26,28–34,37,39–41,43,45,46,48,50,51,53–56, 58–60,63,64,66–112,114,115,118–120,123–125,127
Melena Hematemesis and melena Hematemesis Hematochezia
36% 28% 24% 9%
542 | www.jcge.com Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved. Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
J Clin Gastroenterol
Volume 49, Number 7, August 2015
(1) active arterial spurting or micropulsatile streaming of blood from a minute ( 100 or orthostatic signs. wActive bleeding is defined as spurting/streaming hemorrhage or oozing of blood found during endoscopy.
Copyright
r
The Dieulafoy’s Lesion
to the rapid nature of its onset, which can result in damage to the endoscope.135 Thermal probe monotherapy includes monopolar, bipolar, or heater probe therapy. Heater probe and bipolar electrocoagulation are preferred over monopolar electrocoagulation because tissue destruction is
The Dieulafoy’s Lesion An Update on Evaluation, Diagnosis, and Management David C. Nguyen, MD* and Christian S. Jackson, MD, FACGw
Abstract: Dieulafoy’s lesion (DL) is a persistently wide caliber artery that is observed more frequently at the fifth decade of life in the male population with multiple comorbidities. There are a variety of endoscopic therapies that have been used to treat DL; however, there are no clear guidelines on the best treatment modality. This article systematically reviews the diagnosis, the most commonly reported therapies of DL, and offers a suggested algorithm based upon efficacy of treatment such as initial hemostasis, rebleeding rates, and mortality. Key Words: Dieulafoy’s lesion, upper and lower gastrointestinal bleeding, hemoclips, band ligation, heater probe, bipolar electrocoagulation, local epinephrine injection, argon plasma coagulation, N-butyl-2-cyanoacrylate
(J Clin Gastroenterol 2015;49:541–549)
D
ieulafoy’s lesion (DL) is an uncommon, but potentially life-threatening condition, which can result in sudden, massive gastrointestinal (GI) bleeding. This lesion was described as early as 1884 by Gallard who reported 2 autopsy cases from massive upper GI bleed secondary to “miliary aneurysms of the stomach.” In 1897, Georges Dieulafoy thought that he observed a precursor lesion that bled before it had a chance to develop into a gastric ulcer; thus, calling it “exulceratio simplex.”1,2 Since these initial observations, DL has been diagnosed throughout the GI tract including extragastric locations such as the esophagus, small bowel, and colon.3–7 DL has been referred to as a caliber persistent artery, cirsoid aneurysm, and submucosal arterial malformation.1,3–5,8–11 As endoscopic technology, operator skill and clinician awareness have improved, mortality associated with DL has decreased. However, it still remains a diagnostic and therapeutic challenge. We performed a systematic review of the most current understanding of the pathogenesis, possible risk factors, prognosis, diagnostic modalities of DL. In addition, we evaluated and compiled the initial hemostasis and rebleeding rates for current endoscopic management modalities of DL.
From the *VA Loma Linda Health Care System; and wLoma Linda University and VA Loma Linda Health Care System, Loma Linda, CA. The authors declare that they have nothing to disclose. Reprints: David C. Nguyen, MD, VA Loma Linda Health Care System, 11201 Benton Street, Loma Linda, CA 92357 (e-mail: davidngn@ gmail.com) and Christian S. Jackson, MD, FACG, Loma Linda University and VA Loma Linda Health Care System, 11201 Benton Street, Loma Linda, CA 92357 (e-mail: [email protected]). Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
J Clin Gastroenterol
Volume 49, Number 7, August 2015
MATERIALS AND METHODS Using PubMed we searched for papers by using the following terms: Dieulafoy’s lesion, Dieulafoy lesion, diagnosis, treatment and the reference lists of relevant articles from January 1, 1978 to January 12, 2015. Papers that we included met endoscopic criteria for DL or biopsyproven diagnosis; described location, treatment, initial hemostasis rates, rebleed rates, mortality, and follow-up. The reasons for exclusion are non-English papers, pediatric DL, and lack of sufficient information pertaining to DL.
PATHOLOGY The predominant characteristic of DL is a persistently, large caliber artery, 1 to 3 mm in size, that runs a tortuous path through the submucosa with variable length, protruding through a mucosal defect of 2 to 5 mm.1,2,12 Juler et al2 showed that the surrounding mucosa around DL was histologically normal, lacking findings of ulceration. This artery does not undergo embedding within the wall of the stomach.1,2,10,12,13 The artery has a thick subintimal fibrosis, but no findings of aneurysm, atherosclerosis, or vasculitis.1,2,12 These histologic findings are consistent throughout the GI tract and extraintestinal locations.7,14–18 Miko´ and Thoma´zy12 determined that the average DL measured 1.08 mm in diameter, approximately 10 times the size of a normal artery at a similar mucosa level in the stomach. Submucosal arteries in the lesser curvature arise directly from the left gastric artery as opposed to arising from a plexus of submucosal arteries.1,2 However, there is no similar anatomic explanation elsewhere in the GI tract.
PATHOGENESIS The mechanism of DL’s rupture is unclear. One theory suggests that the path of a DL runs in close proximity to the overlying mucosa; thus, DL’s pulsations may disrupt this epithelium, leading to localized ischemia, erosion of the mucosa, and rupture of the artery.3,12 Another theory proposes that the long-term gastric mechanical forces may bring about the formation of intravascular thrombi, leading to disruption of the vessel wall.2 Stercoral effects of bowel contents may play the initiating factor to the development of mucosal erosion in the lower GI tract.19 Risk factors that have been proposed to bring about the rupture of DL, but have not been connected to DL are comorbidities such as cardiovascular disease or diabetes mellitus, the use of nonsteroidal anti-inflammatory drugs (NSAIDS), aspirin (ASA), warfarin, clopidogrel, steroids, and alcohol.1,20–31 Norton et al20 noted that 51% of their patients took either aspirin or NSAIDs, but the mucosa around the DL was normal. The use of these medications may either play a minor role in the development of bleeding www.jcge.com |
Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
541
J Clin Gastroenterol
Nguyen and Jackson
in DL or more likely a byproduct of patients’ vascular disease.21 To date there has not been large population studies looking at predilection of DL with regard to race, ethnicity or socioeconomic status. Furthermore, no evidence suggests a connection between H. pylori infection and DL.
INCIDENCE The incidence ranges from 0.1% to 5.8% of all nonvariceal upper GI bleeds and for all GI bleeds the incidence is between 0.09% and 1.55%.21,23,28,31–37 Dulic-Lakovic et al’s38 retrospective study noted that small bowel DL accounted for approximately 3.5% of obscure GI bleeds. Schmulewitz and Baillie36 noted that colonic DL accounted for only 0.09% of all colonoscopies performed for lower GI bleeding. The incidence of DL may be difficult to determine due to the challenges of diagnosis.5,22,26,30,36,39–42 Table 1 summarizes the patient profile of the cases reviewed. Of note, DL can occur in pediatric age patients to patients as old as 90 years of age.128,129 Table 2 lists the most commonly reported diseases found in patients with DL. The percent of patients with at least 1 comorbidity can range from as low as 6% to as high as 90%.20,31 The number of patients with 2 or more comorbidities can be found as high as 83%.21 Cardiovascular disease, hypertension, and chronic kidney disease have been hypothesized to explain the weakened arterial vessel at the point of rupture, but some studies have suggested that these comorbidities may be more a product of age.36
CLINICAL MANIFESTATION Patients diagnosed with DL typically are men over 50 years of age with multiple comorbidities and present with an acute painless, massive GI bleeding. Table 3 describes symptoms and signs attributed to DL. The presentation of DL can range from iron deficiency anemia to life-threatening hemorrhagic shock.28,46 Hemodynamic shock can present as high as 87%.28,31,33,51,53,54
LOCATION The majority of DL will predominantly occur in the stomach (about 71% to 74%) with the duodenum as the second most common site (14% to 15%).4,5 It has been noted that 61% to 65% of DLs are found within 6 cm of the gastroesophageal junction.5,23 Within the duodenum, about half were located at the bulb.4,5 Colorectal DL makes up 5% of the established cases.4,5 Esophageal, jejunal, and ileal DL have been rarely reported.
DIAGNOSIS With the shift from surgical and pathologic confirmation of DL to endoscopic diagnoses, Dy et al34 suggested endoscopic criteria to diagnose DL (Fig. 1). The
Volume 49, Number 7, August 2015
TABLE 2. Most Commonly Reported Comorbidities (n = 832)20–24,26,27,33,37,55–58,65
Diseases
Percentage
Cardiovascular disease (coronary artery disease, chronic heart failure, valvular heart disease) Hypertension Chronic kidney disease Diabetes mellitus
33 24.7 11.8 8.2
term “Dieulafoy-like lesion” signifies a lack of histologic evidence.34,110,115 The sensitivity of these criteria to diagnose DL has not been established. Early endoscopy may quickly identify this lesion while it is actively bleeding.5,20,27,37,54,128 Table 4 shows the bleeding characteristics of DL. DL is usually diagnosed on the first endoscopic attempt (Table 4), but in the remaining 20% require a second attempt to diagnose DL. Therapeutic endoscopes with increased suctioning capabilities or shifting the patient’s position during endoscopy to move the intragastric blood can aid diagnosis.34,58 In addition, one can consider using erythromycin or metoclopramide 20 to 120 minutes before upper endoscopy in patients who are highly likely to have fresh blood or clots in the stomach as this will decrease the need to repeat upper endoscopy.130,131 Angiography has been used in cases where endoscopy has failed to identify the cause of bleeding or if the patient is too unstable for endoscopy. It can also serve as a therapeutic option.5 Radiographically, DL will appear as a nontapering, tortuous artery with possible extravasation of blood.5,132 Endoscopic ultrasound (EUS) has been used to confirm the diagnosis of DL. Pulsed and color Doppler ultrasound has aided in the treatment of recurrent bleeds by confirming ablation of DL after injection therapy, band ligation, and hemoclip by documenting the absence of blood flow.25,80,109–111,113,114 In case reports, video capsule endoscopy (VCE) has identified DL in the small bowel, but when the patient is hemodynamically unstable VCE is a less viable of an option than deep enteroscopy.38,94,97,133 As such, VCE’s role in the diagnosis of DL is more appropriate in the setting of an obscure-overt GI bleeding. The advantage of using VCE over deep enteroscopy is that it is noninvasive and can determine the initial route of deep enteroscopy. There are 3 main limitations to VCE, inability to insufflate air, inability to clear the visual field, and lack of therapeutic capabilities.127,134 In practice, deep enteroscopy is the preferred technique of choice to treat hemodynamically unstable patients suspected of small bowel DL.38,97 Dulic-Lakovic et al38 demonstrated that an average of 1.5 attempts were needed to diagnose DL. The optimal route of deep enteroscopy (antegrade or retrograde) is dependent upon the clinician’s suspicion of the location of the bleeding source (proximal or distal) based on a complete VCE examination and
TABLE 1. Patient Characteristics7,13–127 Average age (y) (n = 1068) Sex (n = 1343) Comorbidities (at least 1 chronic condition) (n = 861) Medications (n = 842)
58.3 69% men, 31% women 62.7% 34.4% taking NSAIDs or antiplatelet, 5.3% warfarin
NSAID indicates nonsteroidal anti-inflammatory drugs.
TABLE 3. Symptoms (n = 689)7,14–17,19–26,28–34,37,39–41,43,45,46,48,50,51,53–56, 58–60,63,64,66–112,114,115,118–120,123–125,127
Melena Hematemesis and melena Hematemesis Hematochezia
36% 28% 24% 9%
542 | www.jcge.com Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved. Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
J Clin Gastroenterol
Volume 49, Number 7, August 2015
(1) active arterial spurting or micropulsatile streaming of blood from a minute ( 100 or orthostatic signs. wActive bleeding is defined as spurting/streaming hemorrhage or oozing of blood found during endoscopy.
Copyright
r
The Dieulafoy’s Lesion
to the rapid nature of its onset, which can result in damage to the endoscope.135 Thermal probe monotherapy includes monopolar, bipolar, or heater probe therapy. Heater probe and bipolar electrocoagulation are preferred over monopolar electrocoagulation because tissue destruction is
