Black Pigment Stones Research Articles

Diagnosis of intrahepatic and common duct stones: Combined unenhanced and contrast-enhanced helical CT in 1090 patients

We determined the accuracy of combined unenhanced and contrast-enhanced helical computed tomography (CT) for diagnosis of bile duct stones. During a 12-month period, 1090 patients who underwent combined CT and endoscopic retrograde cholangiography (ERC) or percutaneous transhepatic cholangioscopy (PTC) were enrolled in this study. The results of prospective CT interpretation regarding the presence of bile duct stones were compared with results of endoscopic stone removal, PTC and with surgical results. In 70 patients, detectability of stones on CT was evaluated depending on stone types. Of 1090 study patients, 175 and 299 patients were confirmed to have intrahepatic and common duct stones, respectively. The sensitivity and specificity of combined CT were 73% and 98% for diagnosis of intrahepatic stones and 71% and 97% for common duct stones. Of 70 patients 24, 25, and 21 patients had cholesterol, black pigment, and brown pigment stones, respectively. Eleven of 24 cholesterol stones, 21 of 25 black pigment stones, and 15 of 21 brown pigment stones were detected on combined CT. Combined CT is of limited sensitivity for detection of bile duct stones, especially in Western countries where cholesterol stones predominate. It may be of greater value in populations with a higher incidence of pigment stones. Other complementary imaging modalities are needed for patients with negative CT findings who are highly suspected to have biliary stones.

Incidence of Juxtapapillary Duodenal Diverticula Is Higher in Brown Pigment Stone But Not in Black Pigment Or Cholesterol Stone

Background and Aims: Juxtapapillary duodenal diverticula (JDD) is acquired lesion found more often in older patients. Several studies have suggested association between JDD and bile duct stones. In this study, we wanted to know the incidence of JDD and its association with various bile duct stones together with the success and complication rates of endoscopic retrograde cholangiopancreatography (ERCP) in JDD patients. Materials and Methods: 527 consecutive patients(296 male, 231 female; mean age 63.4 years) having ERCP for various causes were enrolled from January 2004 to November 2005. The ERCP records were retrospectively analyzed. The patients were subdivided into two groups: non-JDD group (n = 398) and JDD group (n = 129). The ERCP procedure related factors and relation with the stones were analyzed. Stones were divided on the basis of their gross morphology and cross-sectional appearance into cholesterol, black pigment, brown pigment stones. Results: JDD was present in 129/527 patients (24.6%). Patients with JDD were more frequently encountered in elderly group and having cholangitis more frequently. The presence of JDD was more common in common bile duct stones {103/129 (79.8%), 193/398 (48.5%), respectively, p = 0.000}, but not in gallbladder stones {44/129 (34.1%), 110/398 (27.6%), respectively, p = 0.170}. Considering the types of bile duct stones, the presence of JDD correlated with brown pigment stones {60/129 (46.5%), 49/398 (12.3%), respectively, p = 0.000}, not black pigment {29/129 (22.5%), 82/398 (20.6%), respectively, p = 0.659} or cholesterol stones {7/129 (5.4%), 39/398 (9.8%), respectively, p = 0.123}. There were no significant differences between two groups in terms of successful cannulation (94.5% vs 96.9%) and stone extraction (92.6% vs 95.6%). The incidence of post ERCP pancreatits was similar in both groups (16.1% vs 18.9%), but bleeding after sphinterotomy was higher in JDD group {26/127 (20.4%), 42/383 (10.9%), respectively, p = 0.017}. Conclusions: JDD is associated with an increased incidence of common bile duct stones especially with brown pigment stones but not with cholesterol or black pigment stones. JDD did not cause technical difficulty at ERCP but appears to be a risk factor for bleedings of endoscopic sphicterotomy.

Molecular Pathogenesis of Hepatolithiasis - A Type of Low Phospholipid-Associated Cholelithiasis

Hepatolithiasis is prevalent in East Asia, including Japan, but occurs much less frequently in Western countries. Hepatolithiasis appears mostly as brown pigment stones (calcium bilirubinate stones). The disease is characterized by its intractable nature and frequent recurrence, requiring multiple endoscopic or operative interventions, in distinct contrast to gallbladder cholesterol or black pigment stones. In view of the lack of information on the pathogenesis, a multidisciplinary approach has been carried out through the Hepatolithiasis Research Group organized by the Ministry of Health, Labor and Welfare of Japan. In this review, the up-to-date data on the molecular pathogenesis of hepatolithiasis with special reference to a defect in phospholipid metabolism are introduced and discussed. Furthermore, a potential medical treatment targeting hepatic phospholipid transporters is proposed as a future therapeutic option for the disease.

Epidemiology, pathogenesis, and classification of biliary stones (common bile duct and intrahepatic)

Gallstones are common in Western countries and Japan. Most gallstones are found in the gallbladder, but they sometimes pass through the cystic duct into extrahepatic and/or intrahepatic bile ducts to become bile-duct stones, causing conditions known as choledocholithiasis and hepatolithiasis. Some 10-15% of gallstone patients concomitantly suffer from bile-duct stones. Bile-duct stones can also be formed in the absence of gallbladder stones, and such primary bile-duct stones are more common in East Asian countries than in the Western world. Thus pathogenesis of primary and secondary bile-duct stones is unlikely to be similar. Furthermore, the gallbladder stones are primarily cholesterol or black-pigment stones, whereas most bile-duct stones are brown-pigment stones (calcium bilirubin stones). Thus, epidemiology, pathogenesis and classification of biliary stones are very likely to differ according to stone location (intrahepatic and/or extrahepatic bile duct).

Dominant Strictures in Patients with Primary Sclerosing Cholangitis-Revisited

TO THE EDITOR: We read with interest Dr. Kozarek's Editorial about our paper on dominant strictures in primary sclerosing cholangitis (PSC) in the March issue of The American Journal of Gastroenterology (1,2). His interpretation is that from a therapeutic standpoint, our paper misses the point. Unfortunately it seems that Dr. Kozarek does not acknowledge the complicated pathophysiology of PSC. As discussed in the Introduction in our paper, intrahepatic cholangiographic changes have more important prognostic significance than extrahepatic cholangiographic changes in patients with PSC (3,4). Our group has demonstrated that high-grade intrahepatic cholangiographic changes but not extrahepatic changes predicted early jaundice and short survival (4). Similar results were reported from researchers from the Mayo Clinic in a study assessing the prognostic value of cholangiographic findings in patients with PSC (3). Consequently, there is no scientific basis for the assumption that improved plumbing (as Dr. Kozarek calls it) of larger, extrahepatic bile ducts improves prognosis in PSC. Importantly, no randomized studies exist demonstrating the benefits of endoscopic treatment in PSC. Thus, the statement concerning the personal experience of Dr. Kozarek that endotherapy can reduce attacks of recurrent cholangitis and abdominal pain in these patients is not in line with evidence-based medicine. Most experienced hepatologists certainly have experienced patients who have had attacks of fever, cholangitis, and jaundice who yet have spontaneously recovered and normalized bilirubin without any treatment. It is also important to remember that in the three published follow-up studies on small duct PSC, abdominal pain was as common in patients with small duct PSC (with normal cholangiography) as in those with large duct disease (5,6,7). Dr Kozarek's sole support for a long-term therapeutic effect of endotherapy is an uncontrolled nonrandomized study in which observed Mayo risk score was better than predicted (8). We also wonder what kind of data support the statement that endotherapy undertaken early enough may also prevent the loss of one liver lobe or another from progressive obstruction. Finally, Dr. Kozarek, presents a novel explanation for fluctuations in liver chemistries in patients with PSC, being due to black pigment stones. This theory has not to our knowledge been put forward in the literature on the etiopathogenesis of PSC. What scientific evidence exists for this statement?

Structural and analytical comparison of gallbladder stones collected from a single patient: studies of five cases.

We observed the gross and fine structure of gallbladder stones collected from five adult patients (cases I-V) by optical photography, radiography, scanning electron microscopy, and backscattered electron microscopy, and then measured the components by energy-dispersive X-ray microanalysis and infrared spectroscopy. From the stones, calcium (Ca) phosphate, Ca bilirubinate, and Ca palmitate or fatty acid Ca were identified. The 3 cholesterol stones (case I) and the 2 brown pigment stones (case II) showed macroscopic homogeneity, respectively. In addition, their fine structure and components were also similar to each other. The black pigment stones (case III) showed macroscopic homogeneity, but they were divided into radiopaque (approximately 30 stones) and radiolucent types (approximately 60 stones). The former had Ca phosphate in the center surrounded with Ca bilirubinate, and the latter was dotted with minute deposits of Ca bilirubinate. The 6 cholesterol stones (case IV) were divided into two types in size. The 5 large stones, of macroscopic homogeneity, had a core region of Ca palmitate and clear concentric rings of Ca phosphate, whereas the smaller stone was almost filled with Ca phosphate deposits in the center. From the different distributions of Ca phosphate, the smaller stone may have been formed later than the 5 large stones. Case V contained 4 stones. The 3 large cholesterol stones, of more or less macroscopic homogeneity, had a core region and concentric rings of Ca phosphate, but 1 smaller stone was dotted with minute deposits mainly containing iron (Fe) and/or silicon elements (rare type). Therefore, the stones of cases III, IV, and V showed considerable heterogeneity, respectively. In many stones, the initial precipitation of Ca salts will have become the nidus, and the concentric rings and dotted deposits of Ca salts may have accelerated cholesterol stone growth. In addition, the dotted deposits of Ca bilirubinate in the black pigment stones and the dotted deposits containing Fe in the rare stone may have become also the nidi.

Gallstone composition: Are childern different?

During a 5-year period (1997-2002) 20 consecutive children (11 boys; median age, 8 years; range, 0.3-13.9 years) underwent cholecystectomy for cholelithiasis at a regional pediatric surgical center. Multiple stones were present in 16 patients (80%). All stones were collected prospectively. Composition studies were performed after grinding an aliquot of stone and examining a layer of crushed powder by Fourier transform infrared microspectroscopy. The relative proportions of each major stone component were assessed: cholesterol, protein and calcium salts of bilirubin, fatty acids, carbonate, and hydroxyapatite. Of the 20 children, 10 had black pigment stones, 2 had cholesterol stones, 1 had brown pigment stones, and 7 had calcium carbonate stones; the latter are exceptionally rare in adults. The composition of pediatric gallstones in this series differs from that found in adults. (J Pediatr 2003;142:435-40)

Hepatolithiasis--epidemiology and pathogenesis update.

Hepatolithiasis or intrahepatic calculi are prevalent in East Asia, including Japan, but occurs much less frequently in Western countries. Hepatolithiasis appears mostly as brown pigment stones (calcium bilirubinate stones) but contain more cholesterol in composition. The disease is characterized by its intractable nature and frequent recurrence, requiring multiple operative interventions, in distinct contrast to gallbladder cholesterol or black pigment stones. Moreover, the most unfavorable complication of the disease is an intrahepatic cholangiocarcinoma. In view of the lack of information on the pathogenesis, a multidisciplinary approach has been carried out through the Hepatolithiasis Research Group organized by the Ministry of Health and Welfare of Japan. In this review, the up-to-date data on the epidemiology and pathogenesis of hepatolithiasis are introduced and discussed. Furthermore, potential medical treatments targeting pathogenetic molecules, which may be important for the etiological process of gallstone formation, are introduced as future therapeutic options for the disease.

Gallbladder motility and cholesterol crystallization in bile from patients with pigment and cholesterol gallstones.

Little is known about gallbladder motility in patients with black pigment stones when compared to cholesterol gallstone patients, or about their relationship to biliary composition, crystallization and stone characteristics. Fasting and postprandial gallbladder volumes were studied by ultrasonography in 49 gallstone patients with pigment (n = 14) or cholesterol (n = 35) stones and 30 healthy controls. After cholecystectomy stone composition, gallbladder wall inflammation, cholesterol saturation index and appearance of platelike cholesterol crystals in bile were evaluated in gallstone patients. Fasting gallbladder volume was significantly (P < 0.05) increased in cholesterol stone patients (31.7 +/- 1.9 mL) but not in pigment stone patients (21.9 +/- 3.1 mL), compared to controls (21.0 +/- 1.5 mL). Postprandial emptying was delayed in patients (half-emptying time: 31 +/- 2 min, 35 +/- 3 min, 24 +/- 2 min in cholesterol stone patients, pigment stone patients and controls, respectively, P < 0.05) and incomplete (residual volume: 43.2 +/- 2.7%, 40.0 +/- 4.3%, 15.8 +/- 1.6% min in cholesterol stone patients, pigment stone patients and controls, respectively, P < 0.05). The inflammation of the gallbladder wall was mild or absent in all cases. Biliary cholesterol saturation index was 152.3 +/- 8.5% and 92.9 +/- 4.8% in patients with cholesterol and pigment stones, respectively (P < 0.01). Whereas cholesterol crystals never appeared during 21 days in biles from patients with pigment stones, crystal observation time in patients with cholesterol gallstone was 5 days (median) and was significantly shorter in patients with multiple (4 days) than in patients with solitary (12 days) cholesterol stones (P = 0.0019). Patients with black pigment stones who do not have excess cholesterol and do not grow cholesterol crystals in bile have decreased gallbladder emptying, although to a lesser extent than patients with cholesterol stones. Thus, gallbladder stasis is likely to put a subset of subjects at risk for the formation of pigment gallstones, and pathogenic mechanisms need to be further investigated.

In vitro sonographic evaluation of common bile duct stones and fragments with a high-frequency microprobe.

This study was conducted to evaluate the sonographic characteristics of common bile duct (CBD) stones and stone fragments scanned in vitro with a high-frequency (20-MHz) microprobe. We sonographically examined 4 whole CBD stones (1 cholesterol stone with radiant cross section, 1 cholesterol stone with lamellar cross section, 1 black pigment stone, and 1 brown pigment stone), 44 fragments of a cholesterol stone (diameter range, 1.1-3.0 mm; mean diameter, 2.0 mm), and 75 fragments of a black pigment stone (diameter range, 1.1-3.0 mm; mean diameter, 2.0 mm). The chemical composition of all stones was analyzed by infrared absorption spectroscopy. All stones and fragments were placed in a plastic box filled with physiologic saline solution for scanning with a 20-MHz microprobe and a 5-MHz probe. Echogenic foci and acoustic shadows revealed at each frequency were compared. At 5 MHz, the 4 CBD stones showed different sonographic characteristics. The cholesterol stone with radiant cross section showed an echogenic focus but no definite acoustic shadow, whereas the cholesterol stone with lamellar cross section showed an echogenic line, several echogenic spots, and a definite acoustic shadow. The black pigment stone showed an echogenic line with a vague acoustic shadow, and the brown pigment stone showed echogenicity of the whole stone and a definite acoustic shadow. At 20 MHz, the 4 stones showed an echogenic line with a definite acoustic shadow. All fragments appeared as echogenic foci at 20 and 5 MHz. Seventy-seven percent (34) and 5% (2) of 44 cholesterol stone fragments cast a definite acoustic shadow at 20 and 5 MHz, respectively. Sixty-nine percent (52) and 15% (11) of 75 black pigment stone fragments cast a definite acoustic shadow at 20 and 5 MHz, respectively. Among fragments 1.5 mm in diameter and smaller, only 45% (5 of 11) from a cholesterol stone and 30% (6 of 20) from a black pigment stone showed a definite acoustic shadow at 20 MHz. High-frequency (20-MHz) sonography demonstrates a definite acoustic shadow more frequently among CBD stones and fragments 1.6 mm in diameter or larger than does low-frequency (5-MHz) sonography, but it does not discriminate the chemical composition.

Epidemiological study on Korean gallstone disease: a nationwide cooperative study.

To clarify the epidemiological characteristics of gallstone disease in Korea and to evaluate the chronological changes in gallstone disease, the authors performed this first prospective nationwide cooperative study. The subjects were 1263 gallstone patients who were admitted at 19 hospitals in Korea from February to July 1997. Questionnaires were recorded on 1263 patients and gallstones were harvested from 1133 patients. The proportion of patients with gallbladder (GB), common bile duct (CBD), and intrahepatic duct (IHD) stones among total gallstone patients was 64.0%, 21.9%, and 14.1%, respectively. GB stones were categorized as cholesterol (58.1%), black pigment (25.2%), and brown pigment (12.1%) stones. CBD stones were classified as brown pigment (76.1%), cholesterol (18.4%), and black pigment (3.5%) stones. IHD stones were classified as brown pigment (61.4%) and mixed (35.6%) stones. Intrahepatic mixed stones had mean cholesterol and bilirubin contents of 63.4 +/- 20.8% and 23.1 +/- 9.9%, respectively. In contrast, IHD brown pigment stones had mean cholesterol and bilirubin contents of 35.1 +/- 20.5% and 39.6 +/- 17.4%, respectively. Our study showed that the type and composition of gallstones in Korea was somewhat different compared with those in the West. This study also demonstrated that there have been chronological changes in the type and composition of gallstones when compared with previous domestic data. Another nationwide cooperative study may be needed to elucidate and confirm the changing pattern of gallstone disease.

Cluster Analysis of Gallstone FT-IR Spectra: Tests on Simulated Mixture Spectra and Comparison between Spectral and Morphological Classification of Human Gallstones

Sixty-four combination spectra of three major gallstone components [i.e., cholesterol, calcium bilirubinate, and calcium carbonate (aragonite)] were simulated in accordance with a “fractal” ternary diagram. Comparison between the original pattern of composition and factorial maps of pretreated spectra makes it possible to show the effects of different normalization procedures (Euclidean norm, spectrum maximum, and area under spectrum set to 1). Cluster analysis of these spectra, depending on different agglomerative links (single linkage, complete linkage, average linkage, and Ward's criterion), was carried out. All the resultant trees yield the same groups, but Ward's criterion best preserves the pattern of the data. More than 100 gallstones from France and Vietnam were classified by using cluster analysis of their FT-IR spectra with Ward's criterion. Seven homogeneous groups of spectra were extracted, which have been significantly correlated to the four morphological types of gallstones: pure cholesterol, mixed cholesterol, brown pigment, and black pigment stones. This analysis also reveals that the morphological groups are not homogeneous in composition, in particular for black pigment stones.

Formation of black pigment gallstone in a hamster model of experimental cirrhosis.

The relationship between liver cirrhosis and the pathogenesis of black pigment stones has not been clarified. We attempted to induce black pigment stone formation in the gallbladders of hamsters. Male golden hamsters were divided into a cirrhosis group and a control group. Liver cirrhosis was induced by administering drinking water containing thioacetamide. The control group was given tap water. Gallstones at 48 weeks after treatment were examined by stereoscopic microscopy and scanning electron microscopy. The copper content of the black pigment stones was analysed by atomic absorption spectrophotometry. Black pigment stones in the gallbladder were detected in 25% of the cirrhosis group. Their surface and cross-section appeared amorphous. Black pigment stones contained copper. We confirmed the formation of gallstones in an animal model of cirrhosis by thioacetamide. Our findings may contribute to the clarification of the relationship between the pathogenesis of black pigment stones and the pathophysiology of liver cirrhosis.

A spectroscopic study of pigment gallstones in China

Spectroscopic studies of various types of gallstones carried out in China are reviewed. Three basic classes of gallstones are surveyed: cholesterol stones, brown pigment stones, and black pigment stones. The emphasis of this review is on brown gallstones. The primary spectroscopic methods used in the studies surveyed are Fourier transform infrared absorption and Fourier transform Raman scattering. Chemical components studied in gallstones include cholesterol, bile pigments, glycoproteins, proteins, bilirubin metal complexes, and salts of calcium and other metals. Further studies are needed characterize the relationship of these components to more complex features of gallstones. © 1997 John Wiley & Sons, Inc. Biospectroscopy 3: 371–380, 1997

A spectroscopic study of pigment gallstones in China

Spectroscopic studies of various types of gallstones carried out in China are reviewed. Three basic classes of gallstones are surveyed: cholesterol stones, brown pigment stones, and black pigment stones. The emphasis of this review is on brown gallstones. The primary spectroscopic methods used in the studies surveyed are Fourier transform infrared absorption and Fourier transform Raman scattering. Chemical components studied in gallstones include cholesterol, bile pigments, glycoproteins, proteins, bilirubin metal complexes, and salts of calcium and other metals. Further studies are needed characterize the relationship of these components to more complex features of gallstones. © 1997 John Wiley & Sons, Inc. Biospectroscopy 3: 371–380, 1997

Gallstone formation and gallbladder bile composition after colectomy in dogs.

A high prevalence of gallstones has been described in patients following colectomy. The aim of this study was to examine whether lithogenicity is attributed to colectomy. In the present study, changes in gallbladder bile composition and the mechanism of gallstone formation after colectomy were examined in dogs. Ten mongrel dogs underwent restorative proctocolectomy. Seven dogs which received sham operations served as controls. Over a 12-week postoperative period, samples of gallbladder bile, formed gallstones and serum were collected and analyzed. In 7 of the 10 (70%) colectomized dogs, gallstones were found in the gallbladder, while the control dogs had no stones. Macroscopically the gallstones were similar to black pigment stones observed in humans. Chemical analysis and Fourier transform-infrared spectroscopy examination revealed that the stones were composed mainly of sodium bilirubinate and proteins, with minor amounts of calcium salts and cholesterol. Significant increases in biliary pH and concentrations of ionized calcium and unconjugated bilirubin were observed in the gallbladder bile of the colectomy group compared with that of the control group. The total bile acid and total bilirubin concentrations were significantly decreased in the colectomy group. Cholesterol crystal nucleation did not occur. The inhibitory effect of gallbladder bile on calcium carbonate precipitation in an in vitro assay system was preserved even after colectomy. In conclusion, proctocolectomy increases the concentration of unconjugated bilirubin in gallbladder bile and induces pigment gallstones which are composed mainly of sodium bilirubinate and proteins since calcium ions and cholesterol are stabilized in dogs.

Pathogenesis and Clinical Presentation of Bile Duct Calculi.

Clearer understanding of the pathogenesis of bile duct calculi and better recognition of the clinical presentation of various clinical disorders caused by biliary stones are essential for proper diagnosis and treatment. This article reviews the pathogenesis of secondary stones (cholesterol and black pigment stones) and primary stones (brown pigment stones), as well as the main features of biliary calculi (pain, obstruction, and sepsis), followed by discussion of the clinical presentations of bile duct stones with gallbladder in situ and after cholecystectomy, and description of the manifestations of primary bile duct stones, cholangitis, primary sclerosing cholangitis, oriental cholangitis, and gallstone pancreatitis.

Pathogenesis and Clinical Presentation of Bile Duct Calculi

Clearer understanding of the pathogenesis of bile duct calculi and better recognition of the clinical presentation of various clinical disorders caused by biliary stones are essential for proper diagnosis and treatment. This article reviews the pathogenesis of secondary stones (cholesterol and black pigment stones) and primary stones (brown pigment stones), as well as the main features of biliary calculi (pain, obstruction, and sepsis), followed by discussion of the clinical presentations of bile duct stones with gallbladder in situ and after cholecystectomy, and description of the manifestations of primary bile duct stones, cholangitis, primary sclerosing cholangitis, oriental cholangitis, and gallstone pancreatitis.

Parietal factors play a basic role in the pathogenesis of some types of black pigment gallstones

Parietal factors play a basic role in the pathogenesis of some types of black pigment gallstones

Black pigment gallstones with cholesterol gallstones in the same gallbladder. 13 cases in a surgical series of 1226 patients with gallbladder stones.

We studied 1312 consecutive patients who underwent surgery for gallstones in the biliary tract at one university hospital in Siena, Italy, with a systematic classification of gallstones found within the gallbladder. Of these patients, 1226 were found to have gallbladder stones; 94 of these had black pigment gallstones. Of these, 13 patients were found to have black pigment gallstones and cholesterol gallstones within their gallbladder. They all had multiple black pigment gallstones, usually very small (all < 6 mm diameter), in association with larger cholesterol stones in the gallbladder lumen. The cholesterol gallstones were single in seven cases, double in two cases, and multiple in four cases. All 13 of these patients with black pigment stones in association with cholesterol stones had histologic evidence of either adenomyomatosis or Rokitansky-Aschoff sinuses in the gallbladder wall. In nine of the 13 patients, the black pigment stones were located both in the gallbladder lumen and in close association with the gallbladder wall (in areas of adenomyomatosis or in Rokitanski-Aschoff sinuses). In the other four patients, the stones were found in close association with the gallbladder wall alone and not freely mobile within the gallbladder lumen. It is concluded that cholesterol stones and black pigment stones may be found in the same gallbladder. This association is infrequent with an incidence of 13 of 1226 (1.06%) in our series. There appears to be some relationship between the formation of the black pigment stones and the presence of adenomyomatosis or Rokitanski-Aschoff sinuses.(ABSTRACT TRUNCATED AT 250 WORDS)