Small bowel ulcers and bleeding: An overlooked yet critical clinical challenge

Abstract

Gastrointestinal (GI) bleeding originating from the small bowel represents a diagnostic and therapeutic challenge, often demanding advanced imaging techniques for accurate identification. Maity et al present a case of a benign ulcerated jejunal GI stromal tumor (GIST) manifesting as overt bleeding, underscoring the importance of considering small bowel neoplasms in obscure GI hemorrhage. Furthermore, recent studies highlight that small intestinal GISTs exhibit more aggressive clinical features compared to gastric GISTs, correlating with worse relapse-free survival and higher rates of GI bleeding. This editorial discusses the implications of these findings and the necessity for comprehensive diagnostic workup in small bowel bleeding.

Key Words: Gastrointestinal hemorrhage; Small intestine neoplasms; Intestinal ulcer; Gastrointestinal stromal tumor; Obscure gastrointestinal bleeding

Core Tip: Small bowel bleeding remains a challenging clinical entity due to its obscure presentation and broad differential diagnosis. This editorial highlights a rare but significant cause—ulcerated jejunal gastrointestinal stromal tumor (GIST)—emphasizing the aggressive behavior of small intestinal GISTs compared to gastric ones. It reinforces the need for a structured diagnostic approach, incorporating capsule endoscopy and enteroscopy, and alerts clinicians to consider both common and rare etiologies, including infectious and genetic causes, when managing small bowel ulcers and bleeding.

INTRODUCTION

Gastrointestinal (GI) bleeding remains a major diagnostic and therapeutic challenge, particularly when its source lies within the small bowel—the so-called "dark continent" of the GI tract[1]. Although small bowel bleeding accounts for a minority of all GI hemorrhages, it is the leading cause of obscure GI bleeding, necessitating multiple hospitalizations, blood transfusions, and extensive diagnostic workups.

The case report by Maity et al[2], describing a jejunal GIST as the etiology of overt GI bleeding, exemplifies the diagnostic difficulties encountered in this context. Advanced techniques such as double-balloon enteroscopy (DBE) and computed tomography (CT) imaging played a pivotal role in identifying and managing the lesion.

The differential diagnosis of small bowel ulceration and bleeding is broad and requires a structured approach integrating clinical, endoscopic, histologic, and radiologic findings[1,3]. While GI stromal tumors (GISTs) are a recognized neoplastic cause of small bowel hemorrhage, more common etiologies include vascular lesions (e.g., angioectasias), nonsteroidal anti-inflammatory drug (NSAID)-induced enteropathy, and inflammatory bowel diseases such as Crohn’s disease. According to Keuchel et al[3], NSAID-related ulcers tend to be small, superficial, and multifocal, with associated mucosal breaks and petechiae, and often occur in older patients with bleeding rather than pain. In contrast, Crohn’s disease is typically associated with deeper, irregular ulcers, transmural inflammation, and accompanying systemic symptoms.

Beyond more common etiologies, several rare but clinically significant causes of small bowel ulceration and bleeding must be considered, especially in immunocompromised patients or those from endemic regions. Intestinal tuberculosis, for instance, can mimic Crohn’s disease both endoscopically and histologically, often presenting with annular ulcers and involvement of the ileocecal valve. Viral infections, such as cytomegalovirus (CMV) and Epstein-Barr virus (EBV), may lead to ulcerative enteritis in immunosuppressed individuals, with CMV typically causing punched-out ulcers and EBV associated with chronic active enteritis and lymphoproliferative disorders[4]. Additionally, chronic nonspecific multiple ulcers of the small intestine and cryptogenic multifocal ulcerous stenosing enteritis are rare genetic enteropathies characterized by superficial mucosal ulcerations and multiple short strictures, often leading to chronic anemia and hypoalbuminemia. These conditions may be mistaken for inflammatory bowel disease, emphasizing the need for genetic testing and long-term follow-up to establish an accurate diagnosis. In addition, to considering neoplastic causes of small bowel bleeding, such as GISTs, a structured diagnostic approach is paramount. According to a practical guide by Havlichek et al[4], video capsule endoscopy (VCE) and multiphasic CT enterography are now standard tools in the evaluation of presumed small bowel bleeding after negative EGD and colonoscopy. VCE offers detection rates between 53% and 73%, while CT enterography is particularly useful in identifying structural lesions such as masses. The selection between these modalities should consider patient-specific risk factors (e.g., capsule retention in Crohn’s disease) and renal function due to contrast exposure. Moreover, DBE not only aids in lesion detection but allows for therapeutic interventions and localization via tattooing. This structured, stepwise approach enhances diagnostic yield and guides appropriate treatment strategies A recent retrospective study by Yang et al[5] compared clinical features and short-term outcomes between gastric and small intestinal GISTs, offering relevant insights. Small intestinal GISTs were associated with significantly higher rates of GI bleeding (P = 0.022), more advanced National Institutes of Health risk category (P = 0.031), and prolonged postoperative hospitalization (P = 0.001) compared to gastric GISTs. Notably, the location of the tumor and the presence of GI bleeding were independent predictors of poorer relapse-free survival.

Furthermore, hemorrhagic GISTs require specific therapeutic considerations. As reviewed by Liu et al[6], surgery remains the mainstay of treatment, especially for tumors > 2 cm or when GI bleeding is present, aiming for complete resection with negative margins (R0). For high-risk tumors or those presenting with bleeding, adjuvant therapy with imatinib (400 mg/day) for at least 36 months is recommended to reduce recurrence risk. Preoperative imatinib may also be indicated in large or metastatic lesions to facilitate resection. Genetic analysis (e.g., KIT and PDGFRA mutations) is essential to guide therapy, as resistance patterns vary depending on the mutational status. Targeted therapies, including second-line agents like sunitinib or regorafenib, may be necessary in cases of imatinib failure[6].

These findings have important clinical correlations with the case presented by Maity et al[2]. The identification of a bleeding jejunal GIST aligns with the observed higher bleeding tendency and more aggressive behavior of small intestinal GISTs reported by Yang et al[5] It emphasizes that small bowel bleeding, particularly when obscure, should raise suspicion not only for benign causes but also for aggressive neoplastic processes. Additionally, the study highlighted the clinical importance of GI bleeding as a prognostic factor, reinforcing the need for early diagnosis and management. These results underscore the urgency of employing advanced diagnostic modalities, such as capsule endoscopy and DBE, in suspected small bowel bleeding to improve patient outcomes (Table 1).

Table 1 Causes of small bowel ulcers and bleeding.

Category	Specific cause	Mechanism of bleeding/ulceration
Neoplastic	Gastrointestinal stromal tumor	Tumoral infiltration and mucosal ulceration
Neoplastic	Lymphoma	Infiltration and tissue necrosis
Neoplastic	Adenocarcinoma	Mucosal invasion and ulceration
Inflammatory	Crohn’s disease	Transmural inflammation and ulceration
Inflammatory	Behçet’s disease	Vasculitis involving submucosal vessels
Inflammatory	Systemic lupus erythematosus	Immune complex-mediated vasculitis
Infectious	Intestinal tuberculosis	Granulomatous inflammation and ulceration
Infectious	Cytomegalovirus infection	Direct viral effect and ulceration
Infectious	Histoplasmosis	Granulomatous infection with ulceration
Vascular	Angiodysplasia	Rupture of abnormal vessels
Vascular	Arteriovenous malformations	Bleeding from vascular malformations
Drug-induced	Nonsteroidal anti-inflammatory drug-induced enteropathy	Direct mucosal injury
Drug-induced	Chemotherapy/radiotherapy injury	Post-therapy mucosal injury
Idiopathic	Isolated nonspecific ulcers	Unknown cause
Idiopathic	Idiopathic chronic ulcerative enteritis	Chronic ulcerative process
Ischemic	Mesenteric ischemia	Mucosal necrosis due to hypoperfusion
Ischemic	Thrombotic microangiopathy	Microvascular lesions and ischemia
Miscellaneous	Radiation enteritis	Radiation-induced vascular/mucosal damage
Miscellaneous	Eosinophilic enteritis	Eosinophilic infiltration causing injury

CONCLUSION

The case report of a bleeding jejunal GIST serves as a crucial reminder of the complexity underlying obscure GI bleeding and the importance of maintaining a wide differential diagnosis. The findings from Yang et al[5] further validate the aggressive nature of small intestinal GISTs and their association with worse outcomes. Awareness of these clinical patterns is critical for timely diagnosis and effective management. We commend the efforts of Maity et al[2] in contributing to the growing body of literature aimed at improving diagnostic accuracy and patient outcomes in small bowel bleeding.