Key points

Cameron lesions

Initially described by Philemon Truesdale in 1924 and then further expanded on in a case series published by Cameron in 1976, Cameron lesions are best described as linear erosions or ulcerations found at the distal end of a hiatus hernia sac in close proximity to the diaphragmatic pinch ( Fig. 1 ). The prevalence of these lesions has been estimated to be between 3% and 5% in the presence of any hiatal hernia and is directly related to the size of the hernia. In patients with large hiatal hernias (>5 cm), the prevalence has been reported to be greater than 12%. Interestingly, a recent study from 2013 found a prevalence of 0.2% in patients hospitalized for overt upper gastrointestinal (GI) bleeding and 3.8% in patients hospitalized for obscure causes of GI bleeding ( Table 1 ). The mechanism for the formation of Cameron lesions is not clearly defined. Many experts thought they occur in patients with hiatal hernias as a result of mechanical trauma and local ischemia caused by repetitive movement of the hernia sac against the diaphragm. Histologically, the changes to the normal mucosa are consistent with ischemia, and biopsy of these lesions can often be confused for ischemic gastritis. Alternatively, there have been some reports in the literature noting that Cameron lesions can result from acid reflux, ischemia, Helicobacter pylori infection, gastric stasis, or vascular stasis. It is likely that these lesions occur from multiple causes, including possible underlying genetic mutations, medical comorbidities, and medications.

Cameron lesions. ( A ) Retroflexed view during upper endoscopy showing a singular Cameron erosion with a black circle. ( B – D ) Cameron lesions as seen on capsule endoscopy denoted by the black arrows in 1C and 1D.

Cameron lesions are often a source for both overt and obscure GI bleeding. They can present as frank hematemesis, melena, or iron deficiency anemia. The hernia neck and sac should be meticulously evaluated during esophagogastroduodenoscopy (EGD) and specifically in retroflexed views as small Cameron lesions can often be difficult to visualize. In addition, it is important for the endoscopist to gauge whether a patient’s clinical presentation is typical for bleeding from Cameron lesions; if it is unclear, then the endoscopist should exclude other causes of GI bleeding.

Bleeding from these lesions is exacerbated by both acid exposure and nonsteroidal anti-inflammatory drug use. In a series of 95 patients with obscure GI bleeding without a clearly identified source on standard endoscopy, push enteroscopy was used to evaluate further. Of the 39 patients with an identifiable source on push enteroscopy, Cameron lesions were the second most commonly missed lesion (21%). In all cases of GI bleeding, especially when an obvious source is not found, Cameron lesions should remain on the differential diagnosis. It is particularly important for Cameron lesions to remain on the differential diagnosis because Cameron lesions can come and go (that is, occur transiently) and can often be missed at the index upper endoscopy.

Treatment of Cameron lesions should be individualized to their presentation. In patients with iron deficiency anemia, acid-suppressive therapy with proton-pump inhibitors following repletion and maintenance of iron stores is generally successful. Conversely, in overt GI bleeding due to Cameron lesions, endoscopic therapy with band ligation for source control has also been reported to be quite successful. Alternative methods of endoscopic hemostasis, such as injection of epinephrine, thermal-contact therapy, and clipping, may be difficult to perform because of its location and movement of the hiatal hernia sac with respiration. Moreover, thermal-contact therapy, such as heat probe or multipolar electrocoagulation, can result in deep ulcers or perforations because of the thin mucosal wall in this area and the lack of underlying fibrous support. It is important to note that when patients present with recurrent or life-threatening bleeding or with persistent and severe iron deficiency anemia from Cameron lesions, surgical intervention may be necessary to repair the invariably large hiatal hernia, thus correcting a major underlying pathogenic mechanism of disease by reducing mechanical trauma caused by repetitive movement of the hernia sac against the diaphragm.

Cameron lesions

Initially described by Philemon Truesdale in 1924 and then further expanded on in a case series published by Cameron in 1976, Cameron lesions are best described as linear erosions or ulcerations found at the distal end of a hiatus hernia sac in close proximity to the diaphragmatic pinch ( Fig. 1 ). The prevalence of these lesions has been estimated to be between 3% and 5% in the presence of any hiatal hernia and is directly related to the size of the hernia. In patients with large hiatal hernias (>5 cm), the prevalence has been reported to be greater than 12%. Interestingly, a recent study from 2013 found a prevalence of 0.2% in patients hospitalized for overt upper gastrointestinal (GI) bleeding and 3.8% in patients hospitalized for obscure causes of GI bleeding ( Table 1 ). The mechanism for the formation of Cameron lesions is not clearly defined. Many experts thought they occur in patients with hiatal hernias as a result of mechanical trauma and local ischemia caused by repetitive movement of the hernia sac against the diaphragm. Histologically, the changes to the normal mucosa are consistent with ischemia, and biopsy of these lesions can often be confused for ischemic gastritis. Alternatively, there have been some reports in the literature noting that Cameron lesions can result from acid reflux, ischemia, Helicobacter pylori infection, gastric stasis, or vascular stasis. It is likely that these lesions occur from multiple causes, including possible underlying genetic mutations, medical comorbidities, and medications.

Cameron lesions. ( A ) Retroflexed view during upper endoscopy showing a singular Cameron erosion with a black circle. ( B – D ) Cameron lesions as seen on capsule endoscopy denoted by the black arrows in 1C and 1D.

Cameron lesions are often a source for both overt and obscure GI bleeding. They can present as frank hematemesis, melena, or iron deficiency anemia. The hernia neck and sac should be meticulously evaluated during esophagogastroduodenoscopy (EGD) and specifically in retroflexed views as small Cameron lesions can often be difficult to visualize. In addition, it is important for the endoscopist to gauge whether a patient’s clinical presentation is typical for bleeding from Cameron lesions; if it is unclear, then the endoscopist should exclude other causes of GI bleeding.

Bleeding from these lesions is exacerbated by both acid exposure and nonsteroidal anti-inflammatory drug use. In a series of 95 patients with obscure GI bleeding without a clearly identified source on standard endoscopy, push enteroscopy was used to evaluate further. Of the 39 patients with an identifiable source on push enteroscopy, Cameron lesions were the second most commonly missed lesion (21%). In all cases of GI bleeding, especially when an obvious source is not found, Cameron lesions should remain on the differential diagnosis. It is particularly important for Cameron lesions to remain on the differential diagnosis because Cameron lesions can come and go (that is, occur transiently) and can often be missed at the index upper endoscopy.

Treatment of Cameron lesions should be individualized to their presentation. In patients with iron deficiency anemia, acid-suppressive therapy with proton-pump inhibitors following repletion and maintenance of iron stores is generally successful. Conversely, in overt GI bleeding due to Cameron lesions, endoscopic therapy with band ligation for source control has also been reported to be quite successful. Alternative methods of endoscopic hemostasis, such as injection of epinephrine, thermal-contact therapy, and clipping, may be difficult to perform because of its location and movement of the hiatal hernia sac with respiration. Moreover, thermal-contact therapy, such as heat probe or multipolar electrocoagulation, can result in deep ulcers or perforations because of the thin mucosal wall in this area and the lack of underlying fibrous support. It is important to note that when patients present with recurrent or life-threatening bleeding or with persistent and severe iron deficiency anemia from Cameron lesions, surgical intervention may be necessary to repair the invariably large hiatal hernia, thus correcting a major underlying pathogenic mechanism of disease by reducing mechanical trauma caused by repetitive movement of the hernia sac against the diaphragm.

Dieulafoy lesion

This vascular lesion was originally referred to as exulceratio simplex in 1898 by the French surgeon Paul Georges Dieulafoy because he thought that it was the first stage of a gastric ulcer. It has also been inaccurately described as an atherosclerotic aneurysm, but this is a misnomer because the caliber of the artery’s walls is uniform throughout and there is no unusual degree of atherosclerosis. A Dieulafoy lesion is a vascular abnormality where persistently large-caliber arteries are present in the submucosa and occasionally the mucosa itself with a small overlying defect. Moreover, the length of the superficially located artery can be several centimeters.

Constant pressure or trauma to a singular area of mucosa ultimately leads to erosions and breakdown of tissue. Similar to the mechanism behind primary aortoenteric fistula (PAEF) formation, it is thought that persistent pressure from these large underlying arteries leads to erosion of tissue and creates a small defect with an exposed vascular wall. The most common location where a Dieulafoy lesion can be found is along the lesser curvature of the stomach, within 6 cm from the gastroesophageal junction in the gastric cardia. Other locations where these lesions have been described include the duodenum (14%), the colon (5%), surgical anastomoses (5%), the jejunum (1%), and the esophagus (1%).

The clinical presentation of this lesion is usually major coffee ground emesis, hematemesis, or melena, without any preceding symptoms. This presentation is followed by recurrent intermittent bleeding that can last for several days. Before the advent of endoscopy, these lesions carried an 80% rate of mortality; however, with current endoscopic and angiographic techniques, this rate has been reduced to 13% or less.

Diagnosis is made during endoscopy and requires a high index of clinical suspicion. In a patient with upper GI bleeding, finding a nonbleeding Dieulafoy lesion can be very challenging. The mucosal defect is often quite small (there is no ulcer) and can be hidden between gastric folds or the vessel itself may constrict and retract after a bleeding episode and thus be almost impossible to see. The lesion itself may also be covered in blood or underneath clot, which also contributes to its elusiveness to identification. The endoscopist should perform a meticulous endoscopic examination of the gastric cardia (where the classic Dieulafoy lesion should be located), and if nothing is seen, the authors suggest using water-jet irrigation to target wash as much of the gastric cardia as possible, particularly along the lesser curvature, with the intent of disrupting a fibrin plug and provoking active bleeding from an underlying Dieulafoy lesion (so-called technique of provocative endoscopy). Once bleeding is provoked, the diagnosis and exact location of a bleeding Dieulafoy lesion are certain and endoscopic therapy can immediately follow. Other methods that have been described to diagnose a Dieulafoy lesion include performing endoscopic ultrasound (EUS) of the stomach and mesenteric angiography.

Dual combination endoscopic therapy is usually recommended to treat a bleeding Dieulafoy lesion ( Fig. 2 ). Endoscopic hemostasis is usually achieved using thermal-contact or mechanical therapy in addition to injection of 1:10,000 diluted epinephrine. Thermal-contact therapy can be performed using heat probe or multipolar electrocoagulation, while mechanical therapy includes band ligation or endoclip placement. The latter 2 both have an equal efficacy, and trends have progressed toward favoring mechanical therapy in the management of these lesions.

Dieulafoy lesions. ( A – C ) Actively bleeding Dieulafoy lesions. ( D ) Dieulafoy lesions after dual combination endoscopic therapy with epinephrine injection and multiple endoscopic clip placement to achieve hemostasis.

( Courtesy of [ A, B ] Drs Sapna Thomas and Saleem Chowdhry, University Hospitals Case Medical Center, Cleveland, OH.)

In the authors’ practice, once bleeding from a Dieulafoy lesion is diagnosed, they often use a through-the-scope endoscopic Doppler ultrasound (DopUS) probe to determine the subsurface route and path of the persistently large-caliber artery (so-called technique of acoustic Doppler mapping) in order that the artery can be treated by endoscopic therapy along the length of its subsurface course. Anecdotally, the authors have found the acoustic Doppler mapping technique to be useful because it permits the endoscopist to treat the entire length of the superficially located artery, which in the authors’ opinion, may reduce the incidence of recurrent bleeding from this disorder. After endoscopic hemostasis is achieved, confirmation of blood flow cessation using a DopUS probe can be used to confirm successful eradication of the lesion. The Dieulafoy lesion should also be endoscopically tattooed to help locate the lesion for repeat endoscopic management if recurrent bleeding were to occur or for surgical wedge resection, if needed.

Additional techniques to control bleeding from a Dieulafoy lesion include endoscopic band ligation or use of a large over-the-scope clip. Angiography with embolization of bleeding source should be pursued in patients who are not candidates for endoscopy or when the site of bleeding is unidentified.

Nonneoplastic gastric polyps: inflammatory fibroid polyps

Inflammatory fibroid polyps (IFPs) are rare submucosal lesions of the GI tract that are semipedunculated protrusions covered by normal mucosa and represent an exceedingly rare cause of upper GI bleeding. In terms of all gastric polyps, which are found in 6% of all EGDs performed in the United States, IFPs represent 0.1% of them. The most common sites where IFPs occur are in the gastric antrum followed by the small bowel. Rarely, they can also occur in the gastric fundus, and very rarely in the esophagus. They were first described by Vanek in 1949, and the term “inflammatory fibroid polyps” was used by Helwig and Ranier in 1953.

Clinical manifestations of IFPs are uncommon because patients are mostly asymptomatic; however, when symptoms do occur, they depend on location of the lesion and include intestinal obstruction, intussusception, abdominal pain, early satiety, gastric outlet obstruction, nausea, vomiting, dysphagia, and rarely, GI tract hemorrhage.

In cases of upper GI bleeding secondary to IFPs located in the upper GI tract, the lesion is usually identifiable on upper endoscopy; however, its endoscopic appearance may be confused with GI stromal tumor, carcinoid tumor, or lymphoma, and definitive diagnosis requires pathologic evaluation. Most IFPs are less than 5 cm in size, but they have certainly been reported to be greater than 10 cm in size. On endoscopy, these lesions are firm and solitary and are often ulcerated. On EUS, IFPs are characterized by an indistinct margin and homogeneous internal echo-pattern and are located within the second or third layer with an intact forth layer. Histologically, IFPs consist of submucosal proliferations of spindle cells, circumferential deposition of fibroblasts around vessels, giving them an onion-skin appearance, and an inflammatory infiltrate primarily comprising of eosinophils. Classically, these lesions are not thought to carry malignant potential, but there have been published reports showing evidence of IFPs being rarely associated with gastric carcinoma.

Given their size, IFPs have been historically resected surgically based on their origin, and exploratory laparotomy is often pursued based on their location. The advancement of endoscopic techniques and increasing prevalence of expertise in endoscopic mucosal resection have allowed for the resections of these lesions endoscopically. Because of their rarity, limited data exist in regards to management, and therefore, each encountered case must be managed in accordance to clinical presentation and local expertise.

Nonneoplastic gastric polyps: gastric hyperplastic polyps

Gastric hyperplastic polyps (GHPs) are a commonly encountered type of gastric polyps. They are equally common in men and women and typically occur in the sixth and seventh decades of life. Although the exact mechanism of pathogenesis is not well defined, these polyps are thought to result from a reparative or regenerative response in the setting of an underlying chronic inflammatory process. Commonly associated causes include atrophic gastritis, H pylori infection, hypergastrinemia, and autoimmune gastritis, among many others. The malignant potential of GHPs is low; however, lesions greater than 1 cm in size and pedunculated morphology are thought to carry an increased risk.

Clinically, GHPs are generally asymptomatic and found incidentally on upper endoscopy performed for alternative indications. Occasionally, patients may present with symptoms including abdominal pain, gastric outlet obstruction, iron deficiency anemia from occult bleeding, and rarely, with overt upper GI bleeding, which occurs more commonly in the setting of anticoagulation, antiplatelet therapy, or other causes of coagulopathy. Although it is quite rare, the exact incidence of overt bleeding from GHP is not well defined ( Fig. 3 ).

( A ) GHP. ( B ) Endoloop ligation of GHP before snare cautery resection. ( C ) Resected GHP. ( D ) Endoclipping of base of polyp after polypectomy.

Endoscopically, these lesions are classically described as smooth, dome-shaped lesions and are usually 0.5 to 1.5 cm in diameter. Larger lesions also occur, frequently become lobulated and pedunculated, and develop surface epithelium erosions, which can result in chronic occult blood loss and iron deficiency anemia. Between 1% and 20% of GHPs have been reported to harbor focal areas of dysplasia, and because of their potential cancer risk, experts have recommended that GHPs larger than 0.5 cm should be completely resected. Endoscopic resection can be performed with snare cautery polypectomy with or without saline lifting or with the assistance of endoloop ligation. If the lesion is too large or resection is unable to be performed, biopsies of the lesions should be taken, and if dysplasia is present or the biopsy is inadequate to exclude dysplasia, then the patient should be referred for surgical wedge resection, which may be able to be done laparoscopically if the endoscopist has previously tattooed the lesion or lesions. According to American Society for Gastrointestinal Endoscopy guidelines, these lesions should undergo surveillance 1 year after initial resection and then at intervals of no more than every 3 to 5 years. If initial pathology is negative for dysplasia, then no further surveillance is necessary. Recent reports have advocated for the use of EUS to further characterize these lesions before resection, but given limited data, no published guidelines exist, and the necessity of EUS to further characterize these lesions should be determined by the endoscopist based on local expertise and specific clinical utility. Endoscopic mucosal resection has been used to resect these lesions to maintain its histologic integrity for pathologic evaluation, but this has not been directly compared with standard snare cautery polypectomy; it is unclear whether endoscopic mucosal resection provides any advantage in clinical management.

Gastric antral vascular ectasia

Gastric antral vascular ectasia (GAVE), initially described by Rider and colleagues in 1953 and then further defined by Jabbari and colleagues in 1984, is another uncommon cause of upper GI bleeding that can be easily confused with portal hypertensive gastropathy (PHG). In fact, it was not until 1995 that a clear distinction was made between GAVE and PHG in cirrhotic patients. Overall, it is an uncommon cause of GI bleeding and is thought to be responsible for approximately 4% of nonvariceal upper GI bleeding in patients with or without portal hypertension.

Classically, GAVE is described as having a “watermelon-striped” appearance in the antrum. However, 30% of patients with GAVE may also have cirrhosis, and it is in this particular group of patients that GAVE can frequently be misdiagnosed as PHG. As opposed to the usual watermelon-striped appearance, in patients with cirrhosis, GAVE can appear as multiple scattered erythematous punctuate lesions in the antrum and can have a very similar endoscopic appearance to PHG ( Fig. 4 ). This similarity is significant because it can lead to misdiagnosis and mismanagement, thereby resulting in continued bleeding and further unnecessary diagnostic procedures, which place the patient at increased risk for complications.

Atypical appearance of GAVE initially mistaken for PHG in a patient with cirrhosis.

It is also important for the endoscopist to be aware that, despite its name, GAVE can occur in locations other than the gastic antrum. For example, GAVE can also be seen within the gastric cardia as an erythematous ring, extending just distal to the gastroesophageal junction and described endoscopically as diminutive vascular ectasia with sparing of the stomach body. GAVE can also occur in the duodenum. Another presentation of GAVE can be in a nodular pattern, known as nodular antral gastropathy, where the mucosa is often raised with visible underlying ectatic vessels.

There are several steps that an endoscopist can take to help prevent confusion at the time of endoscopy and subsequently proceed with appropriate management. In patients undergoing endoscopic evaluation for bleeding or anemia and found to have lesions suspicious for PHG or GAVE, an endoscopic biopsy should be performed to help further delineate the cause. Endoscopists should also be aware that although endoscopic biopsy can be very useful in confirming a diagnosis of GAVE, a negative pathology result does not exclude that the patient has GAVE.

It is important to remember that GAVE is pathologically different from PHG and consists of vascular lesions that contain abnormally dilated and tortuous gastric mucosal capillaries (ectasia) with mural spindle cell proliferation (smooth muscle cells and myofibroblasts), fibrin thrombi, and fibrohyalinosis. Currently, the exact pathogenesis for GAVE remains unclear; however, the microvascular ectasias are thought to be an acquired abnormality as a result of multiple biophysical factors. Mechanical stress from antropyloric dysfunction or from antroduodenal prolapse can lead to traumatic injury to the antral mucosa from inefficient, forceful peristalsis and has been postulated to contribute to the development of vascular ectasias. In addition, elevated levels of several neuroendocrine hormones in cirrhotics: gastrin, vasoactive intestinal polypeptide, 5-hydroxytryptamine, prostaglandin E2, nitric oxide, and glucagon, have been implicated to play a role in the development of GAVE. It is thought that the accumulation of these vasoactive substances, which are incompletely metabolized by the cirrhotic liver, can also contribute to mucosal microvascular damage and ectasia. Hence, the mechanism for GAVE in cirrhotics is attributed to loss of liver function rather than portal hypertension and, interestingly enough, it has been reported to resolve after liver transplantation completely, whereas portal decompressive therapy seems to have no effect. Almost 60% of patients with GAVE have concurrent autoimmune disease, and it has been associated with several other chronic systemic (renal, cardiac, or hematologic) diseases.

Establishing a diagnosis of GAVE has important implications for patient care and its management. Initial management is the same as for any patient with GI bleeding and includes appropriate resuscitation and hemodynamic stabilization. Once this has been performed, the decision to treat lesions due to GAVE depends on the clinical scenario in which it has been discovered. Primary prophylactic treatment is not indicated if the patient is asymptomatic, if the patient does not have iron-deficiency anemia, and if GAVE was an incidental finding at endoscopy. In this scenario, it is reasonable to simply observe the patient clinically. On the other hand, if these lesions are found in the setting of iron-deficiency anemia or active bleeding, first-line treatment involves thermoablative procedures that include thermal-contact and thermal noncontact methods. Examples of thermal-contact treatments include use of heat probe, multipolar electrocoagulation, and radiofrequency ablation. Examples of thermal noncontact treatments include use of argon plasma coagulation (APC) and neodymium:yttrium-aluminum garnet (Nd:YAG) laser. Although there are currently no head-to-head randomized controlled trials available and both are equally effective, the 2 techniques do differ in their safety profile. Overall, there are fewer complications associated with APC attributed to its lack of direct contact with the mucosa, thereby leading to a more superficial burn and reduced risk of perforation; however, pyloric stenosis with gastric outlet obstruction as a result of multiple APC treatments has been described in the literature. Nd:YAG treatment has been associated with the development of gastric ulcers and hyperplastic gastric polyps, and one case of multifocal gastric cancer has also been reported 5 years after multiple therapy sessions.

Newer techniques currently being further evaluated for the endoscopic management GAVE include a mechanically ablative procedure, endoscopic band ligation, which has been shown to result in bleeding cessation, reduced requirement for blood transfusion, and requirement of fewer treatment sessions. A recent review of therapies for GAVE that was published in 2014 found that patients undergoing band ligation were more likely to be free from rebleeding (92%) versus those that are treated with APC (32%). Other newer approaches include the use of radiofrequency ablation, which in some small published studies has shown promising results in patients who fail primary APC therapy for GAVE. Although these results are promising, prospective randomized controlled trials are necessary to establish if one therapy is truly more successful than the other.

At the authors’ institution, they use APC as primary ablative therapy for symptomatic GAVE with radiofrequency ablation being reserved for treatment failures.