October.indd

B.R. Gunna G.R. Yannam N. Kavita* S. Pathak* B.R. Alla
Department of Surgical Gastroenterology,*Department of Nuclear Medicine, Apollo Hospital, Jubilee Hills, Hyderabad, India 500033
Correspondence to: B.R. Gunna, Department of Surgical Gastroenterology, Surgery, Apollo Hospital, Jubilee Hills, Hyderabad, India 500033 Email: gunnabr@hd1.vsnl.net.in

Introduction

Materials and methods

Keywords: Biliary tract, fatty meal-cholescintigraphy
Surg J R Coll Surg Edinb Irel., 1 October 2003, 293-295

Background: The management of patients with symptoms consistent with biliary tract disease but without evidence of cholelithiasis is difficult. This study was undertaken to test the value of cholescintigraphy in predicting the success of cholecystectomy in patients with acalculous biliary tract disorders. Material and Methods: A prospective study was carried out on 73 patients presenting with recurrent upper quadrant pain without documented evidence of gallstones on ultrasound. Fatty meal-cholescintigraphy was performed on all patients and the gallbladder ejection fraction was calculated. Laparoscopic cholecystectomy was performed in patients with ejection fractions of <40%, followed by histopathological analysis and assessment of symptomatic improvement. Results: There were 43 men and 30 women with a mean age of 33.4 years. Forty-one patients had abnormal ejection fractions. All except one patient had a laparoscopic cholecystectomy. The pathological diagnosis of chronic cholecystitis was made in 33 patients and acute on chronic cholecystitis documented in four patients. Five patients had cholesterolosis and two of these had associated chronic cholecystitis. All except three patients had complete relief of symptoms post-operatively with a mean follow-up of 10 months. Conclusion: Modified cholescintigraphy is a useful test for predicting which patients with acalculous biliary tract disease benefit from a cholecystectomy

INTRODUCTION
The management of patients presenting with pain due to suspected biliary tract disease but without documented evidence of gallstones by routine ultrasonography (US) is problematic. This subset of patients may have chronic acalculous cholecystitis, the cystic duct syndrome, gallbladder dyskinesia, cholesterolosis and sphincter of Oddi dyskinesia.¹ They present with recurrent post-prandial upper quadrant pain and dyspepsia. A correct diagnosis is essential, otherwise, patients will be inadequately treated. Surgeons are often reluctant to perform a cholecystectomy without documented evidence of an abnormality in these patients. Increased evidence indicates that at least some of these patients have decreased gallbladder emptying. Quantitative cholescintigraphy is a useful test to detect abnormal gallbladder emptying.^2-8 Several studies have reported that these patients benefit from cholecystectomy.^2-8

We have conducted a prospective study to determine the reliability of fatty meal stimulated cholescintigraphy in patients with acalculous biliary tract disease to establish as to who might benefit from a cholecystectomy and analysed the histopathological findings.

MATERIALS AND METHODS
Between January 2000 and January 2002, 73 patients presented with recurrent right upper quadrant pain, and were evaluated for biliary tract disease in our department. All patients underwent pre-operative US and none had either gallstones or other structural abnormalities of the gallbladder. Upper gastrointestinal endoscopy was done in all patients and was normal. Abdominal computerised tomography (CT) was performed in 11 patients because of clinical uncertainty. The results of pre-operative liver function tests were normal in all patients. All patients received a course of a prokinetic agent (e.g. Mosapride) and omeprazole for a period of six weeks and none had symptomatic improvement. Informed consent was taken from all patients prior to enrolment into the study and the institute ethical committee approved the study.

After an overnight fast, each patient was given five mCi of 99mTc mebrofenin intravenously. Using a large field of view gamma camera and LEAP collimeter (Siemens, E.CAM, Germany), anterior dynamic hepatobiliary images were obtained for 45 minutes at the rate of 1min/frame. Static one minute images were obtained at 45 minutes (mins) and one hour post-injection on a 128x128 computer matrix. This was followed by fatty meal (four ounces of milk and ice cream, containing 300cal and 20gm fat) and post meal static images were obtained every 15 minutes for one hour.⁹

Gallbladder ejection fractions (GBEF’s) were determined from the data acquired at 45 mins pre- and post-meal. Ejection fractions were determined by drawing the region of interest (ROI) manually around the gallbladder and an adjacent background area on a pre meal 45 minutes and post meal 45 min images. A normal GBEF to fatty meal was defined as greater than 40%. An ejection fraction of =40% was considered abnormal. Histopathological diagnoses were obtained in all specimens removed. Patients were assessed during follow-up visits and/ or contacted over telephone to determine the persistence or resolution of their symptoms.

RESULTS
A total of 73 patients were investigated. There were 42 men and 30 women with a male: female ratio of 1.43: 1. The age ranged from 20 to 76 years with mean age of 33.4 years.

Hepatobiliary scintigraphy revealed an abnormal GBEF in 39 patients, delayed visualisation (>60 mins) of the gallbladder in one patient and non-visualisation of the gallbladder in another patient. The test was normal in 32 patients and these patients were excluded from the subsequent study. None of the patients encountered any adverse effects during the procedure. Laparoscopic cholecystectomy was done in all except one patient who refused surgery. Histological abnormalities were noticed in all patients with features of acute on chronic cholecystitis (4), chronic cholecystitis (31), cholesterolosis (3), associated cholesterolosis and mild chronic inflammation (2).

Patients were followed-up for a minimum period of six months. Duration of follow-up ranged from 6 to 24 months (mean 10 months). Thirty-seven patients (92.5%) had symptomatic relief. Three patients had persistent symptoms; two of these patients had persistent biliary gastric reflux on a hepatobiliary scan.

{premeal GB counts- background counts}-{post meal GB counts- background counts} X 100

DISCUSSION
Chronic acalculous disorders of the biliary tract present with recurrent right upper quadrant post-prandial pain and dyspepsia. The pain is presumably due to gallbladder distension secondary to impaired gallbladder motor function. Several pre-operative diagnostic modalities have been used in these patients, which include cholecystokinin (CCK)- stimulated cholecystography, US, cholescintigraphy, duodenal bile analysis for crystals and cholecystokinin gallbladder pain provocation tests.^2-8, ^10-15 All these methods have inherent drawbacks. Dynamic cholescintigraphy is increasing in use and its value has been supported by several nonrandomised and one randomised trail.^2-7 In this test GBEF to cholecystokinin and its analogues is determined to detect impaired function of the gallbladder.¹²

In the present study, we have chosen fatty meal stimulated cholescintigraphy to test the motor function of the gallbladder. It has certain advantages over the ‘conventional’ CCK test in (a) being more physiological, (b) having a more prolonged, consistent and predictable effect, (c) releases cholecystokinin and other stimulatory gastrointestinal hormones such as gastrin and (d) side effects (bradycardia, hypotension, nausea and abdominal pain) observed with CCK, are not seen.¹⁶ However, it has certain disadvantages-endogenous release of cholecystokinin varies depending on the composition of the meal, gastric emptying time, the pressure of pancreatic and small bowel mucosal disease.

The sensitivity, specificity and positive predictive value of CCK cholescintigraphy in patients with impaired gallbladder motor function ranges from 82% to 100%, 87% to 100% and 90% to 100%, respectively.1 Our study (92.5% success rate) confirms the previous reports that an abnormal GBEF predicts the success of cholecystectomy in these patients. In three large non-randomised studies totalling 236 patients, who underwent cholecystectomy on the basis of a low ejection fraction, an improvement or resolution of symptoms was reported in 98.6% of patients.^2,6,7 In addition, its high negative predictive value (91%) should also alert the physician that in the absence of abnormal gallbladder motor function, symptoms are probably not the result of chronic acalculous disease and other pathology should be sought. When interpreted in an appropriate clinical setting, the test can be employed to confirm the gastroenterologist’s and/or surgeon’s clinical impression of symptomatic acalculous biliary tract disease.

Histologically, chronic acalculous cholecystitis is characterised by hypertrophy of the gallbladder wall with or without a concomitant mononuclear cell infiltrate, the presence of Aschoff-Rokitansky sinuses and foamy macrophages.¹ Cystic duct syndrome is presumed to be present if there is fibrosis of the cystic duct, producing at least a 60% luminal narrowing histologically, and/or kinking or adhesions of the cystic duct at surgery; but these findings are difficult to confirm during surgery.^1,17 Gallbladder dyskinesia is caused by an abnormal and/or non-homogenous distribution of CCK receptors within the gallbladder wall and histology will be normal1. In our study, 77.5% had chronic cholecystitis, 10% had acute on chronic inflammation and 12.5% had cholesterolosis. We have not encountered any case of cystic duct syndrome. Incidence of cholesterolosis and clinical outcome after cholecystectomy is poorly evaluated.^2,5-7 The reported incidence of this condition varies from 0 to 62%.2-7,18 Kmiot et al.(1994) reported a 95% improvement rate after cholecystectomy in patients with cholesterolosis.18 In our series, all patients with cholesterolosis had symptomatic improvement.

CONCLUSION
Fatty meal stimulated cholescintigraphy is an excellent predictor of chronic acalculous biliary tract disease and is a safe and cheaper alternative to conventional CCK test. This also predicts accurately which patients benefit from cholecystectomy. We recommend that it should be a mandatory investigation in the diagnostic algorithm of patients with right upper quadrant pain with a normal ultrasound scan and upper gastrointestinal endoscopy. Those patients with atypical symptoms and a normal hepatobiliary scan should undergo further diagnostic testing to identify a more likely source of their abdominal symptoms. Larger studies with long-term follow-up are required to confirm these observations.

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