A Simple and Cost Effective Turn off Fluorescence Sensor for Biliverdin and Bilirubin Based on L-Cysteine Modulated Copper Nanoclusters.

The present article reports the efficiency of L-cysteine modulated copper nanoclusters (L-cys-CuNCs) as a fluorescent probe for the selective determination of naturally occurring bile pigments biliverdin (BVD) and bilirubin (BLR). These pigments were found to quench the fluorescence of L-cys-CuNCs through static processes. Under optimized conditions, the proposed strategy permitted the quantification of BVD and BLR in the range 4.00 × 10-5 to 5.00 × 10-7M and 1.00×10-5 to 1.00×10-6 M respectively with limits of detection 2.33 × 10-7M and 2.29 × 10-7 M. The practical utility of the developed sensor have been investigated in spiked blood and urine samples.

Microstructural diversity of gallstones revealed by spectral microanalyses and their association with hepatic parameters.

BACKGROUND: Gallstones (GS) are formed as a result of impaired metabolic regulation and can be reflected in serum parameters. This study was focused on classifying GS based on spectral microanalysis and identifying the possible role of serum hepatic parameters on GS of different compositions. METHODS: The study included a total of 126 GS from 80 consecutive patients who underwent cholecystectomy for GS diseases in a single center. The composition and microstructure of GS were analyzed using Fourier-transform infrared (FTIR) spectroscopy, field emission scanning electron microscopy (FESEM), and energy dispersive X-ray spectroscopy (EDS). The serum hepatic parameters were studied in order to establish a possible etiologic relationship with GS composition. RESULTS: In the study group, the incidence of GS was higher in females 62 (77.5%) compared with males 18 (22.5%). The mean age was 42.81 ± 13.01 and 43.78 ± 14.4 years for female and male patients, respectively. Based on composition, the GS were assigned to four major groups: cholesterol, pigment, phosphate, and mixed stones. Mixed composition stones totally represented the majority 53 (66.3%), followed by pure cholesterol 23 (28.8%), pigment stones 2 (2.5%), and phosphate stones 2 (2.5%), respectively. Elemental composition revealed the presence of carbon (C), oxygen (O), calcium (Ca), and phosphorus (P) to be major elements along with traces of sodium (Na), magnesium (Mg), aluminum (Al), iron (Fe), copper (Cu), bromine (Br), manganese (Mn), and zinc (Zn). Among serum parameters, total bilirubin, direct bilirubin, indirect bilirubin, serum glutamic-oxaloacetic transaminase, and total protein were higher in patients with pigment GS than cholesterol GS. CONCLUSIONS: Characterization of GS indicates that different types of stones have different characteristics in terms of microstructure, elemental composition, and distribution. Serum hepatic function test profiles showed an association with the compositions of GS.

Altered Bile Transporter Expression and Cholesterol Metabolism in Children With Cholesterol and Pigment Gallstones.

OBJECTIVES: We elucidated pathophysiology of pediatric gallstone disease by assessing liver expression of bile transporters in relation to bile acids and surrogates of cholesterol absorption and synthesis in serum and gallstones. METHODS: RNA expression of canalicular bile transporters in liver biopsies from 32 pediatric gallstone patients and from 6 liver donors (controls) was measured by qRT-PCR (quantitative real-time reverse transcription polymerase chain reaction). Concentrations of cholesterol and precursors, plant sterols and bile acids in gallstones, and in serum of the patients and 82 healthy children were measured. Primary outcomes were the difference in RNA expressions and serum sterol profiles between patients and controls. RESULTS: Cholesterol stones (CS; n = 15) contained cholesterol >42% and pigment stones (PS; n = 17) <9% of weight. CS patients had markedly lower serum plant sterols (absorption) and higher cholesterol precursors (synthesis) than PS patients or healthy controls. CS contained several times more cholesterol precursors and less plant sterols relative to cholesterol than PS, which were enriched by primary bile acids (12-5.2-fold, P < 0.001). Liver RNA expression of ABCG5/G8 was similarly increased 2.5- to 1.8-fold (P < 0.002) in CS and PS patients, whereas PS patients had higher ABCB11 expression (P < 0.05). In PS bile acid concentration correlated with gallstone plant sterols (R = 0.83, P < 0.0001), and ABCG5 expression with ABCB11 expression (R = 0.27, P = 0.03). CONCLUSIONS: In CS, upregulation of ABCG5/G8 expression associates with low absorption and high gallstone content of cholesterol. In PS, activation of bile acid transport by ACBC11 interconnects with hepatic upregulation of ABCG5/G8 enriching PS with bile acids and plant sterols.

Association between diet and gallstones of cholesterol and pigment among patients with cholecystectomy: a case-control study in Korea.

BACKGROUND: The prevalence of cholesterol gallstones is high in Western populations, while pigment gallstones are common in Asian populations. Dietary factors are suggested to be associated with gallstone risk, but their relationship with gallstone type has not been evaluated. This study investigated the association between diet and risk of cholesterol gallstone or pigment gallstone in a Korean population whose dietary pattern and type of gallstone were changed during the last 30 years. METHODS: Patients with cholesterol (n = 40) and pigment (n = 59) gallstones were recruited after laparoscopic cholecystectomy and were compared with those of age- and sex-matched controls without gallstones (n = 99). Dietary intakes were assessed by trained dietitians using a semi-quantitative food frequency questionnaire. Multinomial logistic regression analysis was performed to calculate odds ratios and 95% confidence intervals to examine the associations between diet and risk for type of gallstones adjusted by potential confounders. RESULTS: Patients with cholesterol gallstone consumed more lipid, animal lipid, beef, pork, and fried food than those with pigment gallstones and control, while patients with pigment gallstone consumed more carbohydrate and noodles than patients with cholesterol gallstone and control. In multinomial logistic regression analysis using control as reference group, dietary pattern with high consumption of beef, pork, and fried food was associated with risk of cholesterol gallstones, while there was no association between the risk of pigment gallstone and dietary pattern. In addition, control consumed more alcohol than patients with cholesterol and pigment gallstones. CONCLUSIONS: The present study suggested consumption of fat from meat and fried foods increased the risk of cholesterol gallstone, and intake of carbohydrate from noodles increased the risk of pigment gallstone.

Gunn Rats as a Surrogate Model for Evaluation of Hepatocyte Transplantation-Based Therapies of Crigler-Najjar Syndrome Type 1.

Liver transplantation has been established as a curative therapy for acute and chronic liver failure, as well as liver-based inherited metabolic diseases. Because of the complexity of organ transplantation and the worldwide shortage of donor organs, hepatocyte transplantation is being developed as a bridging therapy until donor organs become available, or for amelioration of inherited liver-based diseases. The Gunn rat is a molecular and metabolic model of Crigler-Najjar syndrome type 1, which is characterized by lifelong unconjugated hyperbilirubinemia due to the lack of uridinediphosphoglucuronate glucuronosyltransferase-1 (UGT1A1)-mediated bilirubin glucuronidation. Gunn rats are convenient for evaluating the effect of hepatocyte transplantation or gene therapy, because the extent of UGT1A1 replacement can be assessed by serial determination of serum bilirubin levels, and excretion of bilirubin glucuronides in bile provide definitive evidence of the function of the transplanted hepatocytes or the effect of gene therapy. The core techniques involved in hepatocyte transplantation in Gunn rats are discussed in this chapter.

Pigmented well-differentiated hepatocellular neoplasm with beta-catenin mutation.

According to the most recent WHO classification of hepatocellular adenomas, a small percentage of inflammatory hepatocellular adenomas presents with mutation in the beta-catenin gene and are at higher risk of malignant transformation. It has been recognized that adenoma-like hepatocellular neoplasms with focal atypia, or in unusual clinical context present with similar cytogenetic and immunohistochemistry characteristics to well-differentiated hepatocellular carcinomas. We report a case of a well-differentiated hepatocellular neoplasm with Dubin-Johnson-like pigment displaying histological features overlapping with a beta-catenin mutated inflammatory adenoma and a well-differentiated hepatocellular carcinoma in a non-cirrhotic liver. The patient was a 48-year-old woman, who was asymptomatic, and had a clinical history of intra-uterine exposure to diethylstilbestrol, previous cancers and past oral contraceptive use. The recently proposed term "well-differentiated hepatocellular neoplasm of uncertain malignant potential" should be applied in such cases to highlight the different pathogenesis and risk of malignancy compared to the typical adenomas, and to suggest a careful and customized clinical management.

Can the type of gallstones be predicted with known possible risk factors?: A comparison between mixed cholesterol and black pigment stones.

BACKGROUND: Pathogenesis of gallstones (GS) is multifactorial and multiple genetic and environmental factors have been identified in different populations for different types of GS with varying prevalence. However the role of the each aetiological factor on the formation of mixed cholesterol and black pigment GS has not being addressed adequately. Hence in this study we attempted to compare known possible risk factors for mixed cholesterol and black pigment GS among two groups of patients with two types of GS. METHODS: The study was done on a cohort of patients with symptomatic GS admitted to the Teaching Hospital Peradeniya, Sri Lanka over a period of 18 months. Clinical and epidemiological data and physical parameters of the patients were recorded and surgically removed GS were analyzed chemically and physically to identify the type of GS. In addition lipid profile was done in all the patients with normal serum bilirubin levels. RESULTS: A total of 86 patients were included in the study. Mixed cholesterol GS was significantly common among females than males (χ2 test, p = 0.029). Mixed cholesterol GS was commonly seen among patients belonging to Moor ethnicity (χ2 test, p = 0.009). Majority of patients with mixed cholesterol GS had body mass index above 25 kg/m2 (χ2 test, p = 0.018). Black pigment GS were significantly common among patients with type II diabetes mellitus (Fisher's exact test, p = 0.035). Further all the patients with chronic haemolytic anaemia and alcoholic cirrhosis had black pigment GS. Age, family history, Fasting Blood Glucose, dyslipidaemia, lipid profile, parity and use of oral contraceptive pills in females, smoking and alcohol intake in males did not differ significantly among patients in the two groups. CONCLUSION: Gender, ethnicity and body mass index can be used to predict the formation of mixed cholesterol GS and black pigment GS.

Common bile duct stones on multidetector computed tomography: attenuation patterns and detectability.

AIM: To investigate the attenuation patterns and detectability of common bile duct (CBD) stones by multidetector computed tomography (MDCT). METHODS: Between March 2010 and February 2012, 191 patients with suspicion of CBD stones undergoing both MDCT and endoscopic retrograde cholangiopancreatography (ERCP) were enrolled and reviewed retrospectively. The attenuation patterns of CBD stones on MDCT were classified as heavily calcified, radiopaque, less radiopaque, or undetectable. The association between the attenuation patterns of CBD stones on MDCT and stone type consisting of pure cholesterol, mixed cholesterol, brown pigment, and black pigment and the factors related to the detectability of CBD stones by MDCT were evaluated. RESULTS: MDCT showed CBD stones in 111 of 130 patients in whom the CBD stones were demonstrated by ERCP with 85.4% sensitivity. The attenuation patterns of CBD stones on MDCT were heavily calcified 34 (26%), radiopaque 31 (24%), less radiopaque 46 (35%), and undetectable 19 (15%). The radiopacity of CBD stones differed significantly according to stone type (P < 0.001). From the receiver operating characteristic curve, stone size was useful for the determination of CBD stone by MDCT (area under curve 0.779, P < 0.001) and appropriate cut-off stone size on MDCT was 5 mm. The factors related to detectability of CBD stones on MDCT were age, stone type, and stone size on multivariate analysis (P < 0.05). CONCLUSION: The radiopacity of CBD stones on MDCT differed according to stone type. Stone type and stone size were related to the detectability by MDCT, and appropriate cut-off stone size was 5 mm.

Metabolomic analyses of faeces reveals malabsorption in cirrhotic patients.

BACKGROUND: The study of faeces offers a unique opportunity to observe cooperation between the microbiome and the metabolism of mammalian hosts, an essential element in the study of the human metabolome. In the present study, a global metabolomics approach was used to identify metabolites differentially excreted in the faeces of cirrhotic patients compared to controls. METHODS: Seventeen cirrhotic patients and 24 healthy individuals were recruited. Faecal metabolites were detected through non-targeted reversed-phase ultra-performance liquid chromatography coupled to electrospray ionization quadrupole time-of-flight mass spectrometry. RESULTS: A total of 9215 peaks were detected. Using unequal variance t-tests, 2393 peaks were observed with P≤0.05, approximately 74.0% of which were due to decreased faecal metabolite concentrations in liver cirrhosis vs. healthy controls. Integrating multivariate data analyses, we identified six major groups of metabolites. Relative levels of identified metabolites were as follows: strong increase in lysophosphatidylcholines, aromatic amino acids, fatty acids, and acylcarnitines, and a dramatic decrease in bile acids and bile pigments. CONCLUSION: With severe hepatic injury in patients with liver cirrhosis, malabsorption occurs along with disorders of fatty acid metabolism, potentially due to changes in gut microflora.

[Effects of Jinhuang Yidan Granule on the bile compositions of primary bile duct pigment calculus patients].

OBJECTIVE: To study the effects of Jinhuang Yidan Granule (JYD) on the bile compositions of primary bile duct pigment calculus patients. METHODS: Sixty-six patients with primary bile duct pigment calculus were randomly assigned to the control group (who took no Chinese medicine) and the JYD group (who took JYD). The bile from T-tube during the operation, 3, 10, and 40 days after medication were examined. The contents of bile acids, bilirubin (conjugated bilirubin, mono-conjugated bilirubin), glucoprotein, calcium ion, beta-glucuronidase, superoxide radical anion, and other components were detected and compared. RESULTS: Three days after taking JYD, the total bile acids increased, the total bilirubin and beta-glucuronidase decreased, showing statistical significance when compared with the control group (P < 0.05). In the JYD group, the total bile acid increased, the total bilirubin, the conjugated bilirubin, the mono-conjugated bilirubin, glucoprotein, calcium ion, beta-glucuronidase, superoxide radical anions decreased 10 and 40 days after medication, showing statistical significance when compared with the control group (P < 0.05, P < 0.01). The level of the total bile acid increased, the levels of the total bilirubin, the conjugated bilirubin, the mono-conjugated bilirubin, glucoprotein, calcium ion, beta-glucuronidase, superoxide radical anions decreased after 40-day medication in the two groups, showing statistical significance when compared with the peri-operative indices of the same group (P < 0 05, P < 0.01). CONCLUSIONS: JYD could significantly improve the pathologic bile compositions of the bile duct calculus, improve the environment of the biliary tract, showing certain preventive and therapeutic effects on bile pigment calculus of the primary bile duct calculus. Better effects may be obtained by long-term taking.

A comparative study of serum lipid profile and gallstone disease.

The diseased gallbladder is one of the commonest specimens submitted to the surgical pathology laboratory in North India. Obesity is associated with a linear increase in gallstone formation. It has been observed that the plasma lipoprotein profile of patients with gallstones differs markedly from that of healthy subjects. Serum lipid profile was done by enzyme kit method. All the gallstones received were categorized morphologically and examined biochemically. The age range of 200 cases was 13 to 77 years with a mean of43.75 +/- 13.39 years. There were 171 females (85.5%) and 29 males (14.5%) with male to female ratio of 1: 5.8. The stones containing both cholesterol and bile pigments were the most common (129 cases, 84.87%); while pure cholesterol stones were seen in 23 cases (11.50%) and pigment stones were infrequent (1 case, 0.65%). On lipidogram of patients in the study group, mean serum total cholesterol was 155.50 +/- 43.03 mg/dL, mean serum triglycerides was 100.49 +/- 45.23 mg/dL, mean HDL cholesterol was 46.71 +/- 15.20 mg/dL, mean LDL cholesterol was 87.94 +/- 36.85 mg/dL and mean VLDL cholesterol was 20.84 +/- 11.97 mg/dL. Serum total cholesterol values were significantly higher in patients older than 39 years as compared to patients < or =39 years (161.44 +/- 42.32 mg/dL vs. 145.79 +/- 32.96 mg/dL, p < 0.05). But the observed mean values in both of these subgroups were within the normal range i.e. <200 mg/dL. No significant difference was observed in the mean serum triglyceride values between male and female patients. The findings of this study did not indicate any role of serum lipid profile in the formation of gallstones. However the higher mean values of serum total cholesterol and serum triglycerides in patients older than 39 years of age may be explained by increasing age.

Predictors of gallstone composition in 1025 symptomatic gallstones from Northern Germany.

BACKGROUND: Gallstones represent a prevalent and costly health problem. The changing epidemiology and the emerging non-surgical interventions for gallstone disease necessitate the definition of target populations for future therapies. This study aimed to define patterns of gallstone composition and identify demographic predictors of gallstone composition in a large sample of symptomatic gallstones from Northern Germany. METHODS: One thousand and seventy-four post-cholecystectomy gallstone specimens were obtained. Demographic and clinical information was provided by questionnaire (N = 1025 independent individuals with complete information). Two samples from each gallstone were analyzed using Fourier transformed infrared spectrometry. RESULTS: The most prevalent substance was cholesterol, which was detected in 95.0% of gallstone specimens. Bilirubin and bilirubinate were present in 30.0% and calcium was detected in 10.0% of the spectra. Ninety-two percent of measurements from the same stone yielded the same "main" substances, indicating a homogenous stone composition in most cases. Female sex and higher body mass index (BMI) were associated with the presence of cholesterol as a main substance in the gallstones (p < 0.001). CONCLUSION: The changing epidemiology of gallstone disease is reflected by a marked shift in stone composition: Only two percent of stones in this study were pigment stones as compared to 91% percent of stones containing cholesterol as a main substance. Obese individuals from Germany with a BMI > 30 kg/m2 have in 95% cholesterol-dominant gallstones and represent a potential target population for non-surgical interventions for the prevention or treatment of cholesterol stones.

Biliary sludge is formed by modification of hepatic bile by the gallbladder mucosa.

BACKGROUND & AIMS: We studied 22 patients with symptomatic microlithiasis to determine whether a contributory role of the gallbladder in the early stage of cholesterol gallstone formation exists. We compared the merits of different methods (ultrasonography and microscopy) and sources (hepatic or gallbladder) of bile samples for diagnosing microlithiasis. METHODS: Paired hepatic and gallbladder bile samples were studied with polarizing microscopy. Nucleation time, bile salts, phospholipid, cholesterol, cholesterol saturation index (CSI), bilirubin, total protein, albumin and mucin concentration were measured. All patients had abdominal ultrasound examination. RESULTS: With polarizing microscopy as the standard, ultrasonography was positive in 13 patients (59%) and negative in 9 (41%). All gallbladder bile samples were positive for microlithiasis by microscopy. Only one hepatic bile sample was positive (P < .0001). There was a disproportional enrichment of total protein, albumin, and mucin (P < .05) in the gallbladder bile and a conversion of bilirubin diglucuronide to monoglucuronide (P < .01). Gallbladder samples had lower CSI but a faster nucleation time (P < .001), which correlates inversely with CSI, total protein, and mucin concentration. CONCLUSION: Biochemical composition and physical chemical behavior of hepatic bile are modified during residence in the gallbladder, contributing to sludge formation. Gallbladder bile has a lower calculated CSI, higher deconjugation of bilirubin, protein and mucin concentration and crystals were present. Hepatic bile samples are inappropriate for microscopic detection of microlithiasis.

A controlled, randomized, double-blind trial of prophylaxis against jaundice among breastfed newborns.

OBJECTIVES: Neonatal jaundice is a greater problem for infants fed breast milk, compared with formula. This study tested the hypotheses that feeding breastfed newborns beta-glucuronidase inhibitors during the first week after birth would increase fecal bilirubin excretion and would reduce jaundice without affecting breastfeeding deleteriously. METHODS: Sixty-four breastfed newborns were randomized to 4 groups, ie, control or receiving 6 doses per day (5 mL per dose) of L-aspartic acid, enzymatically hydrolyzed casein (EHC), or whey/casein (W/C) for the first week. L-aspartic acid and EHC inhibit beta-glucuronidase. Transcutaneous bilirubin levels (primary outcome) were measured daily (Jaundice Meter [Minolta/Air Shields, Hatboro, PA] and Bilicheck [Respironics, Pittsburgh, PA]). All stools were collected, and fecal bile pigments, including bilirubin diglucuronide, bilirubin monoglucuronides, and bilirubin, were analyzed with high-performance liquid chromatography. Follow-up assessments included day 7 body weight, day 6/7 prebreastfeeding/postbreastfeeding weights, maternal ratings, and ages at formula introduction and breastfeeding cessation. RESULTS: The groups were comparable at entry. Overall, the L-aspartic acid, EHC, and W/C groups had significantly lower transcutaneous bilirubin levels than did the control group (75.8%, 69.6%, and 69.2%, respectively, of the control mean, 8.53 mg/dL, at the bilirubin peak on day 4). The L-aspartic acid, EHC, and W/C groups had significantly lower transcutaneous bilirubin levels on days 3 to 7. Fecal bile pigment excretion was greatest in the L-aspartic acid group, significantly greater than control values. There were no significant differences in dosages, follow-up measurements, and maternal ratings. CONCLUSIONS: Use of minimal aliquots of L-aspartic acid and EHC for beta-glucuronidase inhibition results in increased fecal bilirubin excretion and less jaundice, without disruption of the breastfeeding experience. Decreased jaundice in the W/C group, which lacked a beta-glucuronidase inhibitor, suggests a different mechanism.

Bilirubin pigments in the first meconium of newborn infants.

OBJECTIVE: To determine the pattern of excretion of total bilirubin IXa and IXb in the first meconium of newborn infants. METHODS: First two newborns of varying gestational age were selected every week through random sampling from the neonatal unit. Of the 41 newborn infants selected 8 expired before meconium passage, hence the results are from 33 newborns. Meconium was collected and stored at -20 degrees C, protected by aluminium foil. Samples were defrosted, vortex mixed with equal amount of dimethyl-sulfoxide, centrifuged, and analyzed by HPLC. RESULTS: Unconjugated Bilirubin-IXalpha and -IXbeta were identified and quantitative estimation of Bilirubin-IXa done. Bilirubin-IXb was greater than 50% of the total, in the first meconium of the newborn. Amount of bilirubin excreted in meconium was 29.2 - 90.8 mg [0.051 - 0.155 mmol] per sample of meconium passed. Amount was 9.7 mg/ Kg of body weight in term newborn and 12 mg/kg in preterm. CONCLUSION: The amount of bilirubin -IXb decreases and bilirubin-IXa increases with increasing gestational age. Newborns with birth asphyxia (BA) had significantly greater quantity of bilirubin in meconium, compared to infants without BA.

[Expression of MUC3, MUC5AC, MUC6 and epidermal growth factor receptor in gallbladder epithelium according to gallstone composition].

BACKGROUND/AIMS: Gallbladder (GB) mucin is one of the key factors in the gallstone formation. However, there is little information about the diversity of mucin secretion according to the stone composition. Epidermal growth factor receptor (EGFR) functions in proliferation including mucin secreting goblet cell hyperplasia. We compared the expressions of MUC3, MUC5AC, MUC6 and EGFR in the GB epithelium with cholesterol gallstones (GB-chol) group and pigment gallstones (GB-pig group). METHODS: GBs from elective laparoscopic cholecystectomy for the gallstone disease were studied. Stone composition was analyzed by the spectrophotometer. Immunohistochemical stain was performed using each monoclonal antibody. The percentage of stained proportion was scored by the NIH image program and the results were compared between both groups. RESULTS: Total 20 patients were enrolled (10 patients with cholesterol gallstones, 10 patients with pigment gallstones). The percentages of stained proportion for MUC3, MUC5AC, and MUC6 were 42 +/- 27%, 31 +/- 15%, and 17 +/- 9%, respectively in GB-chol group and 32 +/- 22%, 33 +/- 23%, and 15 +/- 10%, respectively in GB-pig group (p>0.05). The expression of EGFR was 50% (5/10) in the GB-chol group and 80% (8/10) in the GB-pig group respectively. CONCLUSIONS: There was no difference in the expressions of MUC3, MUC5AC, and MUC6 between the two groups. Further studies are needed to elucidate the role of EGFR in the gallstone formation.

Hepatoid adenocarcinoma of the urinary bladder.

Hepatoid adenocarcinoma is rare in the urinary bladder with only three well-illustrated previously reported cases. Pathological diagnosis is based on a combination of histological features resembling hepatocellular carcinoma and the positive immunostaining for alpha-fetoprotein. We present the clinicopathological features of four additional cases. The patients were males 66, 85, 61 and 68 years old. Hematuria was the initial symptom in all four patients. Two cases were treated by cystoprostatectomy and the remaining two by transurethral resection of the bladder. On histology, the cases showed a mixture of cells growing in a solid fashion and sheets or anastomosing trabeculae of hepatoid cells merging focally with a secondary glandular pattern of adenocarcinoma. Intracytoplasmic hyaline globules in all and bile production in three of the cases also supported the impression of hepatocytic differentiation. Immunoreactivity for alpha-fetoprotein, low molecular weight cytokeratin, alpha-1-antitrypsin, albumin, epithelial membrane antigen and a striking canalicular pattern when stained against polyclonal carcinoembryonic antigen (CEA), all indicate hepatocellular differentiation. The hepatic nature of the cells was further assessed by detecting the recently incorporated marker hepatocyte paraffin 1, by means of immunohistochemistry and albumin gene mRNA non-isotopic in situ hybridization, both of which had positive signals in all four cases. Three patients died 12, 14 and 19 months after diagnosis. The fourth patient was alive with disease at 26 months of follow-up. In conclusion, hepatoid adenocarcinoma seems to be an aggressive malignant neoplasm that is rare in the bladder whose correct diagnosis may need appropriate immunohistochemical and in situ hybridization means in addition to a complete patient clinical and pathological evaluation. The exact histogenesis and classification of these tumors remains to be established.

Expression of MUC3, MUC5AC, MUC6 and Epidermal Growth Factor Receptor in Gallbladder Epithelium according to Gallstone Composition / 대한소화기학회지

BACKGROUND/AIMS: Gallbladder (GB) mucin is one of the key factors in the gallstone formation. However, there is little information about the diversity of mucin secretion according to the stone composition. Epidermal growth factor receptor (EGFR) functions in proliferation including mucin secreting goblet cell hyperplasia. We compared the expressions of MUC3, MUC5AC, MUC6 and EGFR in the GB epithelium with cholesterol gallstones (GB-chol) group and pigment gallstones (GB-pig group). METHODS: GBs from elective laparoscopic cholecystectomy for the gallstone disease were studied. Stone composition was analyzed by the spectrophotometer. Immunohistochemical stain was performed using each monoclonal antibody. The percentage of stained proportion was scored by the NIH image program and the results were compared between both groups. RESULTS: Total 20 patients were enrolled (10 patients with cholesterol gallstones, 10 patients with pigment gallstones). The percentages of stained proportion for MUC3, MUC5AC, and MUC6 were 42+/-27%, 31+/-15%, and 17+/-9%, respectively in GB-chol group and 32+/-22%, 33+/-23%, and 15+/-10%, respectively in GB-pig group (p>0.05). The expression of EGFR was 50% (5/10) in the GB-chol group and 80% (8/10) in the GB-pig group respectively. CONCLUSIONS: There was no difference in the expressions of MUC3, MUC5AC, and MUC6 between the two groups. Further studies are needed to elucidate the role of EGFR in the gallstore formation.