Although many reports suggest the effectiveness of cholecystectomy for gallbladder dysfunction or dyskinesia (1–3), cholecystectomy as a treatment for gallbladder dysfunction or dyskinesia is not universally accepted. In USA, quantitive cholescintigraphy with cholecystokinin (CCK) is currently used to determine abnormal gallbladder ejection fraction. Several groups revealed that cholecystectomy alleviates the biliary-type pain of patients with a reduced gallbladder ejection fraction (2–5). However, CCK is not allowed for use in humans in Japan. Therefore, it is difficult to diagnose gallbladder dysfunction or dyskinesia. Here, we report a case of gallbladder dysfunction caused by gallbladder arteritis successfully treated by cholecystectomy. We also present evidence that cholescintigraphy with lipid meal loading is useful to diagnose gallbladder dyskinesia and determine cholecystectomy.

A 47-year-old Japanese woman was admitted to our hospital in December 2000, because of upper abdominal and back pain. The patient had been well until one year earlier, when she began to have mild back pain after eating. She had a history of livedo reticularis in 1993, but she had no relevant family history. Three months before admission, she was admitted to another hospital because of progressively worsening abdominal pain. Pancreatic or liver disease was suggested since she had a history of habitual alcohol consumption. However, blood chemical test, abdominal ultrasonogram and computed tomogram (CT), endoscopic retrograde cholangiopancreatography (ERCP) and upper gastric endoscopy examination did not detect any abnormalities other than superficial gastritis. Treatment with famotidine did not relieve pain. She was referred to our hospital for further evaluation of abdominal pain. One month before admission, nitroglycerine was given orally just after abdominal pain occurred, and the pain decreased, although an electrocardiogram showed normal findings.

On admission, perinuclear antineutrophil cytoplasmic antibody (MPO-ANCA) was weakly elevated at 29 EU (normal range: 0–20-EU) and ANA was weakly elevated at 20-fold (homogeneous pattern), however other autoantibodies were negative (Table 1). Although abdominal CT and ERCP examination was performed again at our hospital, no abnormalities were detected (Fig. 1). We considered the possibility of angina of the abdominal arteries based on her clinical episodes. Arteriography examination was performed. Thirty minutes after sugar-water intake, when abdominal pain occurred, enhancement of the superior and inferior mesenteric arteries and the celiac artery and their branches did not demonstrate any stenosis or spasms. After nitroglycerin was administered, abdominal pain was clearly decreased, however, dilations of the arteries were not detected. Next we suspected that the patient had biliary tract or pancreatic dysfunction, therefore cholescintigraphy was performed after obtaining informed consent. Yolk was used as the lipid source. At 20 minutes after injection of ^99mTc-pyridoxyl-5-methyl-tryptophan, just before lipid meal loading, a common bile duct was not detected. In general, a common bile duct and duodenum should be found in normal subjects at this point. At 10 minutes after lipid meal loading, the main bile duct could not be detected yet. At 5 minutes after nitroglycerine was administered, ^99mTc-pyridoxyl-5-methyl-tryptophan quickly flowed to the duodenum through the biliary tract from the gallbladder (Fig. 2), and the ratio of output from the scintigram was less than 1%. This finding strongly suggested dyskinesia of the gallbladder. Cholecystectomy during exploratory laparotomy completely relieved abdominal pain. Histological examination of the surgical specimen showed stenosis of the fine gall bladder artery and infiltration of lymphocytes into the arterial wall (Fig. 3). We therefore diagnosed arteritis and chronic cholecystitis causing dysfunction of the gallbladder.

Gallbladder dysfunction is usually suspected when laboratory analysis, ultrasonographic and abdominal CT examination have excluded the presence of gallstone and other structural abnormalities. Gallbladder dysfunction may be the manifestation of a variety of diseases such as chronic inflammation, cirrhosis, adhesions, diabetes, or other diseases (6). In the present case, abdominal artery disorder or dyskinesia of the gallbladder was suspected because of the nitroglycerine effect. Nitroglycerine dilates the hepato-biliary tract and relieves Oddi's muscles as well as dilating the arteries (7). In the present case, as the histological examination revealed stenosis of gallbladder artery caused by arteritis, nitroglycerine might dilate this stenosis. Arteritis may be one pathogenesis of dyskinesia (8) though it is difficult to definitively diagnose gallbladder arteritis without cholecystectomy. To our knowledge, no case report of gallbladder arteritis described gallbladder function in detail. From this pathogenetical point, this is a rare and interesting case demonstrating that the arterial stenosis due to gallbladder arteritis might have caused gallbladder dyskinesia. Moreover, there are few patients with gallbladder dysfunction who would agree to cholecystectomy. Therefore, correct diagnosis is not always achieved.

Recently, cholescintigraphy has been a useful technology to diagnose dyskinesia and to predict the effectiveness of cholecystectomy based on output ratio after loading CCK. A calculated gallbladder ejection fraction of <35% is considered abnormal and consistent with biliarly dyskinesia (2). Several reports have suggested that cholecystectomy alleviates symptoms in patients with a low gallbladder ejection fraction (2, 3). In Japan, the use of CCK in humans is not permitted. Therefore, the diagnosis of gallbladder dysfunction using the gallbladder ejection fraction is not clinically popular in Japan. However, like our case, lipid meal instead of CCK loading may be helpful for the diagnosis, because it is well known that lipid induces gallbladder contraction and CCK secretion (9, 10). Recently Krishnamurthy and Brown reported that the gallbladder output measured with fatty meal can serve as an alternative method to CCK loading, although the details of the meal and the measurement time sequences influences the fatty meal loading examination (11). As we calculated the gallbladder output of this patient to be lower than 1% according to the formula (2), we considered that cholecystectomy might relieve her abdominal pain.

In the English language literature, this is the first case report suggesting the usefulness of cholescintigraphy with lipid meal loading for gallbladder dysfunction. In patients presenting with abdominal pain without abnormal laboratory data or structural abnormalities, the finding of cholescintigraphy should suggest not only the possibility of gallbladder dysfunction but also promote consideration of cholecystectomy.