Tiny cystine stones in the gallbladder of a patient with cholecystolithiasis complicating acute cholecystitis: a case report
© Qiao et al; licensee BioMed Central Ltd. 2012
Received: 31 January 2012
Accepted: 29 March 2012
Published: 29 March 2012
Cystine stones, the main component of which is cystine, are very common urinary calculi, but are rare in the gall bladder. In animals, there has been only one report of cystine gallstones in tree shrews, and to our knowledge, this is the first report of cystine gallstones in humans.
KeywordsCystine stones Urinary calculi Gallstones
Cholecystolithiasis, or gallbladder stone is a common and frequently encountered disease worldwide [1–4]. Gallbladder stones can be divided into four groups according to their location: intracavitary, cystic duct, intramural, and mucosal stones (small stones adhering to the mucosa) . Based on their main component, gallbladder stones are divided into cholesterol stones, bile pigment stones, mixed stones, and other types [6–9] (including calcium carbonate stones, calcium phosphate stones, fatty acid stones, and cystine stones); this classification is mainly based on the infrared spectrum of the stones. Compared with other types of stones, cystine stones are rare in the gallbladder, although they are common in the urinary system. We report a patient with cystine gallstones.
A 38-year-old woman with a 3-year history of cholecystolithiasis was examined at a local hospital and referred to our hospital for endoscopic gallstone removal without gallbladder excision. When she was hospitalized at our hospital, the acute right upper abdominal pain had persisted for two hours.
On physical examination, no signs of jaundice were seen in the skin or sclera. The patient's abdomen was soft, with no sign of lumps, with tenderness other than rebound tenderness in the gallbladder area. Murphy's sign was positive. Ultrasonography revealed several movable masses of 7 × 10 mm and 7 × 9 mm in size, which were strongly echogenic, with acoustic shadowing in the body of the gallbladder; an immovable strongly echogenic mass of 7 × 10 mm with acoustic shadowing in the neck of gallbladder and cystic duct; and poor sound penetration and a dense, low-light spot in the dark space of the bile. There was no thickening of the gallbladder wall. The gallbladder emptying index was 30%. No obvious abnormalities were seen in the liver, spleen or pancreas.
The patient was diagnosed as having cholecystolithiasis complicating acute cholecystitis and incomplete biliary-tract obstruction. The patient had been given anti-inflammatory treatment after the examination for 2 weeks and the symptoms of acute cholecystitis had disappeared before the operation was schedule, and the patient was strongly in favor of preserving the gallbladder.
Next, some of the small stones and a piece of a large stone were fixed onto the sample table and dried at 60°C overnight, then sputter-coated with gold (ETD-2000, Beijing Elaborate Technology Development Ltd., China) and observed under a scanning electron microscope (EVO LS10; Carl Zeiss, Cambridge, England). The samples were photographed and analyzed with an energy spectrometer (X-Max; Oxford Instruments plc, Oxford, UK). Under scanning electron microscopy, the small stones were found to be composed of hexagonal cystine crystals (30-270 μm), some with prominences on their edges. The energy spectrum indicated that the elemental composition was carbon, oxygen, nitrogen, and sulfur, along with gold from the coating. The large stones were composed of lamellar cholesterol crystals with a thickness of about 1 μm. The energy spectrum indicated that the elemental composition was carbon and oxygen, with gold from the coating (Figure 3C-S).
The spectrum of the small stones indicated that the main component was cystine, and the energy spectrum revealed that the main elements were carbon, oxygen, nitrogen, and sulfur, confirming that these stones were composed of cystine. The spectrum of the large stones indicated that the main component was cholesterol, and the energy spectrum confirmed this, showing that the main elements were carbon and oxygen.
There are no reports of cystine gallstones in any species, with the exception of one report describing sick tree shrews , and in that case, the pathogenesis was not clear. There have been no reports in humans. Urinary cystine stones are mainly induced by cystinuria, an inborn error of metabolism [12–15]. Supersaturation of cystine in the urine leads to the precipitation of cystine crystals, and subsequent formation of cystine stones. We found cystine crystals in our patient's bile sediment, which indicated that the pathogenesis of cystine stones in the gallbladder may be similar to that in the urinary system. However, the patient did not have urinary calculi. It is possible that the presence of stones in the cystic duct led to the incomplete obstruction of the biliary tract and a change in bile metabolism, resulting in the formation of cystine stones.
The mechanism of the formation of cholesterol gallstones involves three main components: supersaturation of cholesterol, gallbladder hypomotility, and kinetic factors [16–26]. Cholesterol is slightly soluble in aqueous media, but is made soluble in bile by forming mixed micelles with bile salts and lecithin. An increase in lecithin or a decrease in bile acid will lead to supersaturation of cholesterol, which produces crystals and precipitates around the core, with spiral growth from the center outwards, and a radial, layered, cord-like arrangement of cholesterol crystals, culminating in stone formation. Patients with incomplete gallbladder emptying were found to have increased total lipid concentrations and some proteins that promote stone formation . The main mechanism for the formation of cholesterol stones, which involves cholesterol supersaturation, gallbladder hypomotility, and kinetic factors, may also lead to the formation of other types of gallstones. Our patient had a normal blood lipid level and a gallbladder emptying index of 30%, indicating poor gallbladder function. These factors may be involved in the formation of both cholesterol and cystine stones.
In conclusion, we report a case of cystine gallstones, a rare type of gallstone, combined with cholesterol stones, in a patient with cholecystolithiasis complicating acute cholecystitis and incomplete obstruction of the biliary duct. The tiny cystine gallstones were adhered to the gallbladder wall and therefore difficult to locate. Surgeons should be aware of the possibility of such stones and ensure that they are removed to reduce the possibility of recurrence. The patient was followed up for 6 months with no abnormal occurrence or recurrence, indicating that the gallstone removal without gallbladder excision has been effective, but she will need to have a longer period of follow-up.
The pathogenesis of cystine stone formation in the gallbladder is not clear, and requires further research. However, this case report provides new insight into the pathogenesis of gallstones. The present research indicates that the composition and genesis of gallstones is more complicated than previously thought, and requires further research and exploration.
Written informed consent was obtained from the patient for publication of this Case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
Tie Qiao, bachelor's degree, Superintendent of the institution, surgeon; Rui-hong Ma, master's degree, researcher; Xiao-bing Luo, master's degree, researcher; Yu-yang Feng, bachelor's degree, surgeon; Xing-qiang Wang, bachelor's degree, surgeon; Pei-ming Zheng, master's degree, researcher; Zhen-liang Luo, doctor's degree, researcher.
Bile pigment stones
Calcium carbonate stones
Calcium phosphate stones
Fatty acid stones
Fourier transform infrared spectroscopy
Scanning electron microscope
X-ray energy spectrometer.
We are grateful to Xiao-feng Wang and Gang Wang in the General Surgery Department of our hospital for their kindly support in providing specimens. We thank other colleagues in the General Surgery Department and the operating room for their enthusiastic help, and the leaders of our hospital for their kind support. We thank the Edanz group China for providing editing assistance for our manuscript.
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