A Retrospective Cohort Study of Gastrosplenic Fistula Secondary to Malignant Etiology: Single-Centre Experience of 5 Cases

Abstract

Gastrosplenic fistula is an uncommon manifestation of malignancy of the stomach and spleen. The aim of this study is to present our 10-year experience on gastrosplenic fistula secondary to malignant etiology. Endoscopy, imaging, and histopathology records of all the patients with gastric and splenic malignant pathologies were reviewed retrospectively. The protocol was approved by the ethical review board of the institute. Descriptive statistics were used to summarize the data. A total of 5 cases were found to have gastrosplenic fistula. Of these 5 cases, 2 were due to large B cell lymphoma of the spleen, 1 was secondary to Hodgkin’s lymphoma of the stomach, 1 case was due to diffuse large B cell non-Hodgkin’s lymphoma of the stomach, and 1 patient was secondary to gastric adenocarcinoma. Gastrosplenic fistula is an exceptionally rare complication of gastrointestinal malignancy. Lymphoma of the spleen is the commonest cause while gastric adenocarcinoma causing gastrosplenic fistula is extremely rare. Most cases occur spontaneously.

Introduction

Gastrosplenic fistula is an uncommon manifestation of malignancy of the stomach and spleen. Though gastrosplenic fistula can occur because of benign disease, malignant pathologies of the stomach and spleen are more commonly associated with this rare disease [1]. Splenic lymphoma is the most common cause of gastrosplenic fistula [2, 3]; 25 cases have been reported in the literature to date. Only 7 cases of gastrosplenic fistula due to gastric lymphoma have been reported. The stomach is the most common site of extra-nodal gastrointestinal lymphomas; however, primary gastric lymphoma is still a relatively rare entity, accounting for less than 15% of all primary gastric neoplasms [2, 3].

Due to the extra-mucosal location of these tumors, presentation with features of frank upper gastrointestinal haemorrhage like hematemesis and malena is rare but may occur consequential to tumor ulceration, erosion of a major vessel, or formation of a gastrosplenic fistula [3, 4].

The aim of this study is to present our 10-year experience on gastrosplenic fistula.

Materials and Methods

Endoscopy, imaging, and histopathology records of all the patients with gastric and splenic malignant pathologies who were managed in surgical unit 4 in our institute between January 2008 and December 2017 were reviewed retrospectively. Patients who were found to have gastrosplenic fistula at presentation and also those who developed gastrosplenic fistula before, during, or after initiation of any form of therapy were included in this study.

Records of these patients were then reviewed in detail. The parameters such as age, gender, clinical features, associated comorbidities, investigations, treatment modalities including surgery, complications, prognosis, and follow-up were evaluated. The protocol was approved by the ethical review board of the institute.

Statistical Analysis

Descriptive statistics were used to summarize the data.

Results

Of 5 cases of gastrosplenic fistula, 2 were secondary to diffuse large B cell lymphoma of the spleen, 1 was due to diffuse large B cell non-Hodgkin’s lymphoma of the stomach, 1 was due to Hodgkin’s lymphoma of the stomach, and the fifth case was secondary to adenocarcinoma of the stomach (Table 1). There were 3 male and 2 female patients; the youngest patient was 40 years old while the oldest was 54 years of age. There were no associated comorbidities except for the history of pulmonary tuberculosis in one patient.

Table 1.

Clinical presentation, diagnostic evaluation, and management of five cases of gastrosplenic fistula. CECT, contrast-enhanced computed tomography; GI, gastrointestinal

S. no	Clinical presentation	Age/sex	Associated comorbidity	Imaging studies/endoscopy/biopsy	Management	Follow-up/prognosis
Case 1	Pain in the upper abdomen, non-bilious vomiting, weight loss—3 months duration, haemetemesis—2 episodes	45/M	No	CECT: irregular thickening of the greater curvature, curvilinear track extending from the wall of the stomach to a localized heterogeneous collection in the region of the superior pole of the spleen measuring 5.5 × 4.7 × 3.7 cm. Upper GI endoscopy: thickening of the gastric mucosa with loss of gastric folds extending from the cardia involving the fundus, lesser curvature, and greater curvature. Biopsy was non-specific	Total gastrectomy with splenectomy and perigastric D1 lymphadenectomy. HPE: diffuse large B cell non-Hodgkin’s lymphoma of the stomach. IHC: CD-20, CD-3, LCA positive. Postoperative chemotherapy (CHOP) was given	14 months, disease free
Case 2	Pain in the upper abdomen, weight loss, anorexia, low-grade fever—1 month, haemetemesis—2 episodes in 3 days	54/M	Pulmonary tuberculosis 5 years back	Thickening of the entire stomach wall, a small track running from the cardia of the stomach to the hilum of the spleen with a collection in the splenic hilum of size 3.5 × 4.2 × 2.2. Upper GI endoscopy: loss of gastric rugosity, no ulceration	Total gastrectomy with splenectomy. HPE: Hodgkin’s lymphoma of the stomach, received chemotherapy	18 months, disease free
Case 3	Pain of the abdomen, haemetemesis, fever—2 days, vomiting, anorexia and weight loss, malena—1 month	51/F	No	CECT: irregular thickening of the gastric wall with a maximum thickness of 25 mm at the greater curvature with a track extending from the greater curvature to the mid body of the spleen, enlarged perigastric lymph nodes. Upper GI endoscopy: thickening of the gastric mucosa involving body and antrum and scope was not negotiable beyond the body of the stomach	Total gastrectomy with splenectomy and perigastric D1 lymphadenectomy. HPE: gastric adenocarcinoma	Died on 8th postoperative day due to sepsis
Case 4	Anorexia, fever, weight loss, non-bilious vomiting, diffuse abdominal pain—2 months	40/F	No	CECT: superior pole splenic mass with thickening of the greater curvature of the stomach at the level of the cardia, with a curvilinear track extending from the posterior wall of the stomach to a heterogenous collection in the region of the superior pole of the spleen. The track had contrast with air foci suggestive of fistulous communication between the stomach and the spleen. Upper GI endoscopy: loss of gastric folds in cardia with no ulcer or obvious thickening	Splenectomy with gastric wedge resection of the greater curvature, chemotherapy (R-CHOP), HPE: diffuse large B cell lymphoma of the spleen	32 months, disease free
Case 5	Pain in the upper abdomen, vomiting, fever, anorexia, weight loss—3 months	40/M	No	CECT: splenic mass lesion at the mid pole of size 6.8 × 8.7 × 8.8 with a track extending from splenic mass lesion to the cardia of the stomach on the posterior wall, upper GI endoscopy: ulcerative lesion next to the cardia in the greater curvature on posterior wall	Splenectomy with gastric sleeve resection. Chemotherapy (R-CHOP), HPE: diffuse large B cell lymphoma of spleen	34 months disease free

All the 5 cases developed gastrosplenic fistula (GSF) spontaneously before any form of intervention. Pain in the upper abdomen was the most common symptom present in 4 patents while one patient presented with diffuse abdominal pain. Other common presenting symptoms were vomiting, weight loss, and anorexia present in 4, 4, and 3 patients, respectively. Of 3 patients who had haemetemesis, 1 patient had severe intractable bleed. One patient presented with malena. The mean duration of symptoms was 2 months (range 1–3 months). Pallor and hard upper abdominal lump was the most common clinical finding present in 5 and 4 patients respectively.

Contrast-enhanced computed tomography (CECT) was done in all the cases and supported the diagnosis. The consistent findings on CECT were thickening of the gastric wall and track extending from the spleen to the stomach wall with collection at the splenic end of the track. Upper gastrointestinal endoscopy was also done in all the cases and showed loss of gastric rugosity in 3 cases. There was no gastric ulceration in any of the case. All of the patients were HIV negative. Endoscopic ultrasound is not available in our institute, so, it was not done in any of the case.

Four cases underwent elective surgery while 1 patient underwent emergency resectional surgery. Total gastrectomy was done in 3 cases, while gastric sleeve resection and wedge resection was done in 1 case each. Splenectomy was done in all the 5 cases. All the patients received adjuvant chemotherapy—2 patients received CHOP regimen while the other 2 received R-CHOP regimen. One patient with GSF secondary to adenocarcinoma of the stomach died 6 weeks after surgery before initiation of chemotherapy. The other 4 patients with lymphoma with GSF recovered well and were on a regular following treatment.

Discussion

In 1962, Scoville et al. were the first to report GSF, describing two patients with GSF due to splenic lymphosarcoma [5]. They termed it “aerosplenomegalie” by virtue of the presence of air within an enlarged spleen on imaging studies, while the other case was diagnosed at autopsy [5]. GSF occurs because of close proximity of the spleen with the greater curvature of the fundic part of the stomach, and also the presence of gastrosplenic ligament [3, 6, 7].

GSF is a rare complication of neoplastic and acute or chronic inflammatory pathologies of the stomach and spleen [1–3]. Malignant pathologies of the spleen followed by the stomach are the most commonly implicated etiological factors [1, 2]. Lymphoma of the spleen is the most common malignant pathology associated with gastrosplenic fistula formation [1–3]. Out of 36 cases of malignant gastrosplenic fistula reported in the literature, 25 were secondary to splenic lymphoma, non-Hodgkin’s lymphoma being more common than Hodgkin’s lymphoma. In the literature, there are 7 reported cases of GSF due to gastric lymphoma and 1 due to gastric adenocarcinoma, while 1 patient developed GSF due to splenic metastases from colonic adenocarcinoma [8]. Of 5 of our cases, 2 were due to splenic lymphoma, 2 were due to gastric lymphoma, while 1 case was secondary to gastric adenocarcinoma.

A total of 10 cases of GSF due to benign causes, such as splenic abscess (3 cases), splenic tuberculosis (1 case), post-traumatic (1 case), Crohn’s disease of the stomach (1 case), and gastric ulcer perforation (4 cases), have been reported [9].

GSF formation may occur spontaneously or during or after full course of chemotherapy for lymphoma [8, 10, 11]. Of 36 reported cases, GSF developed spontaneously in 28 cases while its formation followed chemotherapy in 8 cases [9]. All of our cases developed gastrosplenic fistula spontaneously. Diffuse large B cell type gastrointestinal malignant lymphoma is more frequently associated with GSF formation because of its aggressive nature and causes widespread serosal infiltration and necrosis [12, 13]. The rate of perforation and subsequent GSF formation due to acute tumor lysis syndrome following adjuvant chemotherapy has been reported in up to 5% of lymphoma patients [14]. The spontaneous GSF formation is more commonly seen with lymphomas of the stomach as compared to adenocarcinoma because of the necrosis caused by largeness of the gastric lymphoma and the absence of desmoplastic reaction in lymphomas when compared with adenocarcinoma, and it occurs in advanced stages of the disease [11].

In addition to the features of primary malignant or inflammatory pathology, the common presenting clinical features of GSF are epigastric or left upper quadrant pain (up to 60% of patients), anorexia and weight loss (53% of patients) [15], and splenomegaly (up to 80% of patients) [16]. Pain in the upper abdomen, fever, anorexia, and weight loss were the most common symptoms in our patients. GSF leads to other complications such as haemetemesis which can be severe in nature. Of 36 reported cases of GSF due to malignant causes, haemetemesis has been reported in 3 cases while 2 patients had a history of malena and 1 patient had occult haemorrhage presenting as heme positivity in stool [9]. All the 3 patients with GSF presenting with haemetemesis were cases with primary splenic lymphomas [3, 4, 17]. Three of our cases presented with haemetemesis and it was of severe nature in 1 case. A high index of suspicion is warranted in patients with splenic or gastric lymphoma presenting with gastrointestinal haemorrhage.

Contrast-enhanced computed tomography (CECT) scan is the imaging study of choice for diagnosis of GSF as it is superior to other imaging studies and endoscopy [12]. The features suggestive of GSF are the presence of air or air-fluid levels in the spleen on non-contrast CT [7], the presence of the tract from a cavitary lesion in the stomach to a cavity in the spleen on CECT [4, 12], and CT angiography showing involvement of vessels with a fistulous tract [4, 12]. It should be kept in mind that in the presence of involvement of vessels, the cavity or mass in the spleen could be a haematoma. Retrograde CT cystography is helpful in differentiating a lesion which appears as splenic abscess on CECT [18]. Upper gastrointestinal series and barium studies have also been quoted to demonstrate the fistula [19].

In the diagnosis of GSF, endoscopy is inferior to CT scan; however, it provides supportive evidence and helps in obtaining a biopsy as the lesion often ulcerates the stomach. Endoscopy is the initial investigation of choice in patients with upper GI bleed. The classical endoscopic findings suggestive of GSF are the ulcerated cavity on the greater curvature or in the fundus, gastric folds converging on the greater curvature, bright red central oozing, or it may rarely show direct communication with the spleen [7, 12, 20]. CECT before the endoscopic biopsy is valuable as it can show the presence of haematoma of involvement of vessels.

The role of surgical resection in splenic as well as gastric lymphoma is debatable [12]. The mainstay of management is chemotherapy, and the majority of patients with splenic and gastric lymphoma without complications are now being treated with chemotherapy and radiotherapy [12, 21]. In majority of the reported cases, who underwent any form of surgical resection following chemotherapy, residual malignancy was rarely demonstrable [10, 11, 13, 22].

Surgical treatment is helpful in providing definite tissue diagnosis and pathological staging. Surgical intervention is indicated for prevention and management of life-threatening complications like perforation and haemetemesis. To control haemetemesis, splenic artery embolization is preferred initially [4]; if it fails to control the bleeding, emergency surgical resection is indicated. Two cases have been reported in the literature where emergency total gastrectomy with splenectomy was done [4, 23], while splenic artery embolization followed by total gastrectomy and splenectomy was performed in one case [4]. Total gastrectomy with splenectomy with open approach was done in 3 of our cases, while splenectomy with gastric sleeve resection and splenectomy with gastric wedge resection were done in 1 case each. Emergency splenectomy with total gastrectomy was done in 1 case for haemetemesis, while all other cases underwent elective surgery. There is only one published report of successful excision of the fistulous tract along with gastrectomy using the laparoscopic approach [24]. All of our patients received chemotherapy after surgery and recovered well.

Conclusion

Gastrosplenic fistula is a rare complication of malignancies of the gastrointestinal tract; lymphomas arising from the spleen are the commonest cause. Gastric lymphoma is the other common malignancy that can result in GSF formation while gastric adenocarcinoma is an exceptionally rare cause of GSF. Most cases occur spontaneously but at times it can be secondary to tumor necrosis during the course or following chemotherapy. A high index of suspicion of GSF is necessary in patients with gastric or splenic lymphomas especially in the context of unrelenting upper GI bleed. CECT is superior to endoscopy in diagnosing GSF. An iconic depiction of the fistulous tract or contrast/fluid (pus) and air in the spleen is pathognomic. Endoscopy usually demonstrates an ulcer in the region of the gastric fundus near the greater curvature and also provides with a tissue biopsy and precise histopathological typing and staging prior to definitive management. Most cases are due to NHL, diffuse B cell, or histiocytic type. Standard chemotherapy is indicated for definitive management of lymphoma, and resectional surgical therapy is advocated to circumvent acataclysmal bleed. Surgical resection includes splenectomy along with segmental, partial, or total gastrectomy depending on the site and extent of involvement of the stomach. The development of gastrosplenic fistula in patients with adenocarcinoma of the stomach is a poor prognostic factor.

Declarations

Conflict of Interest

The authors declare no competing interests.