Gallstone ileus without bilioenteric fistula years after bypass surgery for Crohn's disease. Case report and clues to etiology of a neglected cause of obstruction.

INTRODUCTION: Gallstone ileus is a very rare cause of bowel obstruction. Patients suffering from Crohn's disease are at increased risk of developing gallstone disease, especially when terminal ileum is involved. Gallstone ileus can occur, but etiology remains controversial. We report on a case of such a rare condition, illustrating etiology and treatments. PRESENTATION OF CASE: A patient with long-standing Crohn's disease, who had undergone ileotransverse bypass for ileocaecal involvement 40 years before, presented with cramp-like abdominal pain. Imaging was consistent with a gallstone ileus with no evidence of bilioenteric fistulae. DISCUSSION: At surgery, we found gallstones stuck at the site of ileotransverse anastomosis. No bilioenteric fistulae were found. Due to disease progression, many enteric fistulae were found, requiring a massive bowel resection. The diverted segment may have been responsible of gallstone formation, and etiology is discussed. Recovery after surgery was uneventful, but the patient required continued nutritional support.
CONCLUSION: Physicians dealing with Crohn's disease patients with bypassed segments should keep in mind, the increased risk of gallstone formation, in order to not overlook gallstone ileus. Early suspect and diagnosis may allow for less aggressive approaches. A diverted segment should always be removed, and long-term follow-up encouraged.

Introduction

Gallstone ileus (GI) is a rare condition that can be due to either a fistula between the gallbladder and the digestive tract or the migration through the papilla Vateri of small stones, which can increase in volume into the intestine.

Crohn’s disease (CD) is a known risk factor for cholelithiasis, because of the alteration of the enterohepatic circulation of bile salts, with subsequent intestinal inflammation due to their reduced reabsorption. A correlation between CD and GI is uncommon. Few cases are reported in the literature, but etiology remains unexplored [1], [2]. We herein describe the case of a CD patient presenting with GI without bilioenteric fistula, and propose a detailed etiological pathway underlying such a rare but challenging complication.

Presentation of case

A 74-year-old man with long-standing CD, also suffering from diabetes mellitus, was referred to our Hospital for constipation, lower abdominal pain, fever with shivering, and weariness lasting since 15 days. He was taking oral antiplatelet agents for a stroke occurred two years before. Medical, family, and psychosocial history were unremarkable. The patient was operated on elsewhere 40 years before for ileocaecal CD, receiving an ileotransverse colon bypass with side-to-side anastomosis.

The patient was frustrated, and distressed. A psychiatric consultation was offered, and found no significant disturbances needing treatment, although a low mood was observed. At physical examination, he was dehydrated, he had blood pressure of 100/60 mmHg, pulse rate of 90 bpm, and was breathing normally. The abdomen was moderately distended. Inspection showed swelling of the lower abdominal quadrants, covered by erythematous and thin skin. Palpation was moderately painful. The bowel-sounds were low. The rectal examination revealed empty ampulla recti.

Laboratory tests were as follows: WBC: 25.4 × 103/uL with neutrophilia, RBC: 3.48 × 106/uL, Hb: 12.3 g/dl, creatinine: 1.5 mg/dl, glycemia: 225 mg/dl. The liver function was poor and serum bilirubin levels were normal. A plain abdominal X-ray showed air-fluid levels and some calcium concretions with sharp outlines at the level of mesogastrium/hypogastrium (Fig. 1). A CT scan was carried out, and five oval-shaped concretions were found along the gut, four at the site of the anastomosis (ranging between 2.5 and 5 cm), and another one at the level of right colon (1.5 cm). Fig. 2 depicts a 3D reconstruction of the CT scan, performed to better classify and locate the formations. An ultrasound scan was advocated for better evaluation of the gallbladder and bile ducts, and to exclude fistulae. The gallbladder was contracted, with thickened walls and sclerotic margins, and contained a gallstone of 1 cm in diameter. The bile ducts were not dilated. All these findings raised suspicion of a GI without bilioenteric fistulae.

Fig. 1

Plain X-ray.

A plain chest and abdomen X-ray, showing air-fluid levels and calcium formations (arrow) at the level of mesogastrium/hypogastrium.

Fig. 2

3D-CT reconstruction.

A 3D reconstruction of CT scan, showing the gallstones stuck at the level of the anastomosis, and another little stone in the right inguinal fossa, inside the right colon (arrow).

The patient underwent emergency laparotomy (Fig. 3). Free serous fluid was found in the peritoneum. The loops of the small intestine appeared affected with an inflammatory process, and were adherent to the abdominal wall, covered with purulent material. Several enteroenteric fistulas have developed between the bypassed right colon and small bowel loops, making it difficult to dissect these free. A massive bowel resection of the small bowel and right colon was hence needed. The transverse colon was closed and a terminal jejunostomy was fashioned, avoiding an anastomosis due to poor health status and prolonged surgery with blood loss. Four calcified concretions were removed through the disconnected ileotransverse anastomosis, where the largest was impacted. The other concretion was found in the resected right colon, and presumably passed the anastomosis before impaction of the largest stone. Cholecystectomy was deemed necessary. Pathology confirmed the diagnosis of CD and the nature of the 5 calcified gallstones (calcium bilirubinate).

Fig. 3

Intra-operative findings.

The small bowel loops proximal to the site of gallstone impaction (ileotransverse anastomosis) are grossly distended.Purulent fluid is found and removed at the site of excluded bowel segment (terminal ileum and right colon).The surgeon checks that the gallstone does not pass the ileotransverse anastomosis.After disconnection of the anastomosis of the ileotransverse bypass, the impacted gallstone and other three stones are extracted. Another stone was found the right colon.

The patient recovery was uneventful, and he was discharged on postoperative day ten with parenteral nutrition support. The improved health status gradually lead to a better quality of life perception as assessed by psychiatrists.

Discussion

GI is an unusual finding and accounts for 1–4% of cases of laparotomy for bowel obstruction [1], [2]. It is more frequent in elderly, female patients. GI occurs in approximately 25% of cases in the small intestine. The most common sites of impaction are represented by the terminal ileum, the ileocaecal valve, and more rarely the jejunum, duodenum, stomach, and in 4% of patients, the colon [2]. Clinically, it can present with the triad of Rigler [2], [3], [4], [5]: pneumobilia, dilated small bowel with paucity of air in the large bowel, and opacity in the right iliac fossa.

A fistula between the gallbladder and the digestive tract is the most common cause of GI, but the gallstones may be found in the intestine without evidence of fistula [1] CD, and inflammatory bowel diseases (IBD) in general, are risk factors for gallstones due to the dysfunction of the enterohepatic circulation of bile salts. Pathogenesis of IBD relies on complex autoimmune mechanisms along with genetic and environmental factors, which are not completely understood yet [6], [7], [8], [9]. The immune system of CD patients is extremely active [8], [9], and may play a role in determining the higher incidence of gallstones through both intestinal endoluminal mediators and systemic factors. Long disease duration and bacterial overgrowth may play an important role. Parente et al. [3] confirmed the correlation between CD and gallstones in 415CD patients, and suggested that several CD-specific risk factors were more strongly associated with gallstone disease than age, sex and BMI. Specifically, disease duration >15 years, >3 clinical recurrences, >3 high-dose steroid treatments, ileal resection >30 cm, ≥2 total parenteral nutrition treatments, >3 hospitalizations and >40 days of stay in the hospital increased the risk of gallstones [3].

A hypothesis concerning etiology of gallstones in CD patients with disease involving the terminal ileum is suggested by the frequent high glycine/taurine conjugation ratio, a constant finding when the enterohepatic circulation is interrupted by ileal disorders or surgery [10]. This is believed to be due to unavailability of taurine compared with increased demands for synthesis of conjugated bile salts. The overgrowth of the gut microflora also plays a role. The so-called “stagnant loop syndrome”, first described by Tabaqchali et al. in 1968 [11], suggests that in patient with blind loops there is excessive bacterial deconjugation of bile salts [12], and therefore, presumably increased demand for reconjugation. However, experimental models in rats, though confirming such observation after ileal resection, documented a rapid adaptation to the new function [13].

The case of our patient seems to fit in with hypothesis of reduced absorption of taurine due to ileal disease, combined with excessive bile salt deconjugation due to the bacterial overgrowth (stagnant loop syndrome) in the diverted ileocolonic segment (Fig. 4).

Fig. 4

A pictorial sketch of the suggested pathogenesis of gallstone ileus in our patient.

The ileotransverse anastomosis, allowing bypassing the strictured terminal ileum. Though stool transit is restored, active disease is not removed, and inflammation persists. If the diseased segment is not excised, it is responsible of disease progression and risk of malignancies.The excluded bowel segment is still reached by the fecal stream. Stagnant feces are responsible of bacterial overgrowth with increased de-conjugation of bile salts. In addition, disease affecting the terminal ileum leads to reduced levels of taurine because of reduced bile salts absorption. This is reflected in increased glycine/taurine ratio and gallstone formation. Large stones tend to settle in the gallbladder, whereas small stones can migrate in the bile duct, and in the duodenum. G: glycine; T: taurine.As long as gallstone formation continues, the gallbladder can angulate and fistulae can develop between the gallbladder or Hartmann's pouch and the cystic duct, or between the gallbladder and the intestine. Large stones can migrate in the bowel and cause gallstone ileus. In the case of our patient, no fistulae were identified between the gallbladder and the adjacent structures, suggesting that stones migrated into the gut, and subsequently enlarged. One stone became stuck into the anastomosis (“G” in the drawing), causing obstruction with dilation of proximal small bowel loops.

Surgical treatment of CD requires extensive expertise, with complex surgical and combined treatments [14], [15]. Intestinal bypass surgery, much used in the very early years of CD surgery, is almost abandoned nowadays. However, it can be advocated in frail patients with extensive ileocaecal disease, as a bridge to definitive surgery [16]. This should be carried out six months after bypass surgery, in order to remove the diseased bowel when the patient is in optimal general status [16]. Leaving behind, the bypassed segment untreated raises several, serious concerns. First, it is a source of continuing inflammation, and may be responsible of disease persistence rather than relapses. In the case of our patient, this was responsible of progression of CD with fistulae, or evolution toward a penetrating pattern from an inflammatory/stricturing CD. Second, in the mid-term, it can determine bacterial overgrowth in the excluded segment, which actually is still reached by the fecal stream. This was responsible of recurrent episodes of steatorrhoea and malaise in our patients, ultimately leading to increased formation of gallstones. The passage of stones in the small intestine resulted in GI due to their “nucleation”, accretion, and impaction in the stenotic ileocolonic anastomosis. This required emergency laparotomy with massive resection. Lastly, it increases the risk of malignancies in the long-term, especially in patients with long-standing CD. IBD are known risk factor for malignancies, via inflammation-driven pathways, different from those observed in sporadic cancerogenesis [17], [18], [19]. Thus, if the diseased segments are not removed, patients are exposed to unacceptably high risks of carcinoma. This should be posed into perspective in IBD patients, as disease can occur at any age [20], [21], [22].

The surgical treatment of GI consists of enterotomy, extraction of the gallstones, and search of a possible bilioenteric fistula. Treatment of bilioenteric fistula, if present, and/or cholecystectomy at the time of emergency laparotomy are debated [5]. The surgical approach is still variable depending on the characteristics of the patient and the underlying disease, and based on the judgment of the surgeon. When possible, the laparoscopic approach is feasible [4]. Our patient needed laparotomy due to the complexity of the disease. If the bacterial overgrowth hypothesis is verified, a role for probiotics and antibiotic combinations cannot be ruled out [23], [24].

Timely diagnosis allows for less extensive approach, and might reduce the risk of impaired quality of life and self-perception. This is relevant, as CD are at increased risk of psychiatric disturbances, more pronounced when disease is active or uncontrolled [25].

Conclusion

GI is rare, but in patients with inflammatory diseases predisposing to stricture of the bowel, it can be responsible of serious complications. If diagnosis is not timely, surgery is mandatory.

At our knowledge, this is the first case of GI in a CD patient with a diverted bowel segment, without bilioenteric fistulae, and offers etiological perspectives on such a rare condition. Our findings are new, but needs to be confirmed in larger samples of patients. Nonetheless, the rarity of such condition makes it difficult to obtain stronger evidences.

Physicians dealing with CD patients should keep in mind the increased risk of gallstones in their patients in order not overlook GI. Diagnosis at an early stage may allow elective and less aggressive surgical approaches. A diverted segment should always be removed, and patients should be encouraged to attend long-term follow-up after surgery.

Patient perspective

At the time of admission, the patient was frustrated and worried because of the unexplained reasons underlying his condition.

After treatment, the health status improved significantly but gradually. Fortunately, the patient did not develop psychiatric disturbances requiring treatment, but he felt that a more readily suspected diagnosis as well as more appropriate information and timely removal of the diverted segment would have avoided further nuisances.

The patient is currently in good health status and would have undergone the treatment again.

Conflicts of interest and source of funding

None.

Ethical approval

The IRB of the Second University of Naples gave consent to conduct the case report description (observational study) on 4 November 2014.

Author contribution

Gianluca Pellino: participated substantially in conception, design, and execution of the study and in the analysis and interpretation of data; also participated substantially in the drafting and editing of the manuscript.

Giuseppe Candilio: participated substantially in conception, design, and execution of the study and in the analysis and interpretation of data.

G Serena De Fatico: participated substantially in conception, design, and execution of the study and in the analysis and interpretation of data.

Rosa Marcellinaro: participated substantially in conception, design, and execution of the study and in the analysis and interpretation of data.

Giulio C Formicola: participated substantially in conception, design, and execution of the study and in the analysis and interpretation of data.

Antonio Volpicelli: participated substantially in conception, design, and execution of the study and in the analysis and interpretation of data.

Guido Sciaudone: participated substantially in conception, design, and execution of the study and in the analysis and interpretation of data.

Gabriele Riegler: participated substantially in conception, design, and execution of the study and in the analysisand interpretation of data.

Silvestro Canonico: participated substantially in conception, design, and execution of the study and in the analysis and interpretation of data.

Francesco Selvaggi: participated substantially in conception, design, and execution of the study and in the analysis and interpretation of data; also participated substantially in the drafting and editing of the manuscript.

Consent

Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.

Guarantor

Gianluca Pellino.