• Journal of Yeungnam Medical Science
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• v.23 no.2
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• pp.152-161
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• 2006

Carcinoma of the gallbladder is an uncommon but highly malignant tumor with a poor five year survival rate. Early detection is very important for successful treatment because this tumor is very hard to cure in cases where it has advanced beyond the reach of surgical treatment. The purpose of this review was to evaluate risk factors for carcinoma of the gallbladder and determine the best management approach.. Solitary polys, more than one cm are considered to be predisposing factors for gallbladder carcinoma when they are found to be echopenic, sessile, and with a high cell density. Anomalous union of the pacreato-biliary duct(AUPBD) without a choledochal cyst is also considered to increase risk for gallbladder carcinoma. A polyps size of more than one cm and an AUPBD are indications for prophylactic cholecystectomy. The presence of gallstones is a well-established risk factor for the development of gallbladder carcinoma; risk appears to correlate with the stone size and the duration of chronic cholecystitis. Metaplastic changes of the gallbladder epithelium present with chronic cholecystitis and may indicate a premalignant lesion. Abnormal forms of cholecystitis such as xanthogranulomatous or a porcelain gallbladder also have malignant potential; cholecystoenteric fistula as well as bacterial infection of the gallbladder(typhoid, helicobacter species) also has malignant potential. In this review, the risk factors associated with carcinoma of the gallbladder are summarized with special attention to gallstones, polyps, AUPBD, and chronic inflammation.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.8
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• pp.3747-3752
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• 2014

Background: Gallbladder carcinoma (GBC) is the most common carcinoma of the biliary system. Among its research models, orthotopic xenograft models, important research tools, have been rarely reported in the literature however. Aim: To explore establishment of an orthotopic xenograft model and to evaluate the advantage and disadvantage as compared with other models. Materials and Methods: Subcutaneous xenograft and orthotopic xenograft models of gallbladder carcinoma in nude mice were established and compared with human gallbladder carcinomas. Results: For the orthotopic xenograft model and clinical gallbladder carcinomas, the lymph node metastatic rates were 69.2% and 53.3% (p>0.05); ascites generation rates, 38.5% and 11.7%(p<0.05); liver invasive rates, 100% and 61.7%(p<0.05); and lymphatic vessel densities (LVD), $10.4{\pm}3.02$ and $8.77{\pm}2.92$ (p>0.05), respectively. In the subcutaneous xenograft model, no evidence of ascites generation, lymph node metastasis and liver metastasis were found, and its LVD was lower ($4.56{\pm}1.53$, p<0.05). Conclusions: Compared with the subcutaneous xenograft model, the orthotopic xenograft model better simulates clinical gallbladder carcinoma in terms of metastasis and invasion, which may be attributed to the difference in microenvironment and LVD.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.1869-1874
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• 2016

Background: Errors in surgical pathology diagnosis can have serious consequences for the patient. Since the final product of a surgical pathology lab is the report, errors can be picked by reviewing reports of cases. Aim: To determine the frequency and types of error in surgical pathology reports of cases signed out in 2014 in a laboratory in Karachi, Pakistan. Materials and Methods: All surgical pathology reports in which changes were made in the original report after sign out and an amended report was issued were included. Errors included: (1) misinterpretations; (2) missing critical information; (3) erroneous critical information; (4) misidentification; and (5) typographic errors. Results: Errors were identified in 210 cases (0.37%). These comprised 199 formalin fixed specimens and 11 frozen sections. The latter represented 3.8% of a total of 2,170 frozen sections. Of the 11 frozen section errors, 10 were misinterpretations. Of the 199 permanent specimens, 99 (49.7%) were misinterpretations, 65 (32.7%) belonged to missing critical information category, 8 (4%) belonged to erroneous critical information category, 8(4%) were misidentifications, 16(8%) were typographic errors while 3 cases (1.5%) were other errors. Most misinterpretations occurred in the gastro intestinal, liver and pancreato biliary tract (23.2%) and breast (13.1%). Another 87 cases were reviewed on the clinicians' request. However diagnosis after review remained the same as the original diagnosis. In 49 out of these (56.3%), additional workup was performed at the time of the review. Conclusions: Our findings were similar to other published studies. We need to develop documented procedures for timely review of cases to detect errors.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.759-764
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• 2013

Background: The high recurrence rate after hepatic resection in hepatocellular carcinoma (HCC) is a major obstacle to improving prognosis. The objective of the present study was to explore the function of genistein, a soy-derived isoflavone, in enhancing the inhibitory effect of cisplatin on HCC cell proliferation and on tumor recurrence and metastasis in nude mice after curative hepatectomy. Methods: Proliferation of human HCC cells (HCCLM3) was detected by 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) assay. Synergistic effects of genistein and cisplatin were evaluated with the median-effect formula. Nude mice bearing human HCC xenografts underwent tumour resection (hepatectomy) 10 days post implantation, then received intraperitoneal administration of genistein or cisplatin alone or the combination of the two drugs. 33 days after surgery, recurrent tumours and pulmonary metastasis were evaluated individually. MMP-2 level in recurrent tumours was detected by immunohistochemistry and real-time PCR; MMP-2 expression in HCCLM3 was detected by immunocytochemistry. Results: Genistein and cisplatin both suppressed the growth and proliferation of HCCLM3 cells. The two drugs exhibited synergistic effects even at relatively low concentrations. In vivo, mice in the combined genistein and cisplatin group had a smaller volume of liver recurrent tumors and fewer pulmonary metastatic foci compared with single drug treated groups. Cisplatin upregulated the expression of MMP-2 in both recurrent tumours and HCCLM3, while genistein abolished cisplatin-induced MMP-2 expression. Conclusions: Genistein reinforced the inhibitory effect of cisplatin on HCC cell proliferation and tumour recurrence and metastasis after curative hepatectomy in nude mice, possibly through mitigation of cisplatin-induced MMP-2 upregulation.

• Parasites, Hosts and Diseases
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• v.31 no.2
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• pp.83-90
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• 1993

We performed bromodeoxyuridine (BrdU) staining to observe the proliferation pattern of epithelial cells on the biliaJy mucosa in Clonorchis sinensis infection. Albino rats were infected with 100 metacercariae each and their livers were processed for histopathological observation after BrdU injection. Five to six sites in the liver of a rat were selected for paraffin section, and stained immunohistochemically to visualize BrdU incorporating cells. The flukes were mainly in the common bile duct and right or left hepatic bile ducts. The proportion of stained epithelial cells in the infected bile ducts where the worms were found on the section was 2.9-10.2% at 1 week after infection. 7.3-12.8% at 2 weeks, 7.3-13.4% at 5 weeks, and 8.4-14.8% at 15 weeks while in the non-infected ducts o to 2.7% cells were stained. The stained cells were mainly at the base of the mucosal layer. It is suggested that mucosal epithelial cells of the bile ducts infected with C. sinensis become hyperplastic mainly by direct and local stimulation of the worms.

• Korean Journal of Veterinary Pathology
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• v.6 no.1
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• pp.41-48
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• 2002

Oval cell is considered as facultative precursor cells for both hepatocytes and biliary cells, as well as origin of hepatocellar and cholangiocellular carcinoma (CCC) during carcinogenesis or toxic liver injury. To clarify the cellular origin or differentiation of cholagiocarcinogensis, the fate of carcinogen-induced oval cells was pathologically and phenotypically chased in Syrian golden hamster liver after Clonorchis sinensis (CS) infection which would give rise to a promoting effect. Two week treatment of hamsters with 0.005% diethylnitrosamine (DEN) followed by 2 week treatment of 1% 2-acetylaminofluorene (AAF) under choline deficient diet resulted in massive proliferation of BrdU labeleed and PCNA positive oval cells showing various distinct morphology, histochemical and immunohistochemical phenotypes for GGT, cytokeratin 19 and OV-6. Oval cells also frequently form ductular-like structures or phenotypically show hepatocyte-like characteristics. After CS infection, the oval cells showed sequential morphological changes to atypicl proliferating bile ductules and all hamsters thereafter developed well differentiated and anaplastic CCC at 16 week after CS infection. In electron microscopy, some bile ductules were constructed by intermediate oval cells and bile ductular cells surrounded by basement membrane. The results of this study strongly suggest that CCC developed in the present study were originated from hepatic stem-like oval cells, supporting the theory of stem cell origin of cancers. In addition, this hamster model would be valuable for the molecular mechanistic study during chemical-triggered cholangiocarcinogenesis.

• Journal of Pharmaceutical Investigation
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• v.28 no.2
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• pp.73-80
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• 1998

In order to elucidate the effect of N-demethylation on the in vivo metabolite kinetics, especially hepatic first-pass effect of trimebutine(TMB), the N-demethylation of TMB to N-monodesmethyl trimebutine(N-TMB) was studied in rats. TMB(10 mg/kg) and N-TMB(10 mg/kg) were injected into the femoral and the portal vein, respectively. And the pharmacokinetic parameters were obtained from the plasma concentration-time profiles of TMB and N-TMB determined by the simultaneous analysis using high-performance liquid chromatography. It was supposed that these drugs were almost metabolized in vivo because the urinary and biliary excreated amounts of TMB and N-TMB were lower than 0.1% of the administered dose. According to the hepatic biotransformation model and metabolic pathways of TMB proposed, it was found that the fraction of systemic clearance of TMB which formed N-TMB in liver$(G_{mi})$ was 0.826, that of TMB which furnishes the available N-TMB to the systemic circulation$(F_{mi})$ was 0.083, and the absolute hepatic bioavailability of N-TMB formed trom TMB$(F_{mi.p})$ was 0.1. These results showed that TMB was suspected of the sequential hepatic first-pass metabolism and N-demethylated by 82.6%. Therefore, the residue would be hydrolyzed by the esterase in the liver. That is, the ability of N-demethylation of TMB was 4.75-fold larger than that of hydrolysis by the esterase in rats.

• Journal of Veterinary Clinics
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• v.25 no.5
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• pp.363-369
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• 2008

The aim of this study was to establish an experiment animal model for easy diagnosis and monitoring effect of treatment of cholelithiasis by cholesterol and mixed gall stone. In 12 adult beagle dogs, five dogs there were in the control group and seven dogs in the experiment group with ligated cystic duct. General clinical signs were recorded, CBC and blood chemistry were examined. Control group and experiment group were evaluated every 2 weeks for a period of 20 weeks. The results were (1) Total blirubin, cholesterol, alanine aminotransferase (ALT), aspartate aminotransferase (AST) activity were significantly higher in the experiment group with ligated cystic duct than control group during 2-8 weeks. (2) Total alkaline phosphatase (TALP) activity was significantly higher when compare with control group during 2-8 weeks. Bone alkaline phosphatase(BALP) activity was increased slightly between 2 and 8 weeks but was decreased between 10 and 20 weeks. (3) Blood urea nitrogen (BUN) was decreased between 2 and 8 weeks. After 10 weeks, this was in normal range. (4) On complate blood count (CBC), $Ca^{2+}$ and P were not changed until 20 weeks. (5) On clinical signs in experimental group, they observed a depression, yellow color of mucus membrane and conjunctiva, xanthinuria and xanthochromic. The present study showed that the experimental animal model with ligated cystic duct was a useful model to study biliary tract disease.

• Archives of Pharmacal Research
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• v.28 no.2
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• pp.203-208
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• 2005

Scoparone is a major component of the shoot of Artemisia capillaris (Compositae), which has been used for the treatment of hepatitis and biliary tract infection in oriental countries. In the present study we observed that, scorparone exhibited no cytotoxic effect in unstimulated macrophages, but reduced the release of nitric oxide (NO) and prostaglandin $E_2\;(PGE_2)$ upon stimulation by IFN-${\gamma}$/LPS or LPS. The inhibitory effects were found to be in conjuction with the suppression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in IFN-${\gamma}$/LPS stimulated RAW 264.7 cells. Moreover, scoparone also attenuated the production of tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-$1{\beta}$ and IL-6 in LPS-stimulated RAW264.7 cells. These results suggest that scoparone decreases the production of the inflammatory mediators such as NO and $PGE_2$ in macrophages by inhibiting iNOS and COX-2 expression.

• Archives of Pharmacal Research
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• v.26 no.1
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• pp.83-88
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• 2003

KR-984055 is a new oral cephalosporin antibiotic with activity against both gram-positive and gram-negative bacteria. Lipophilic ester-type prodrugs of KR-984055, i.e., KR-999001 and KR-999002, have been synthesized in an attempt to increase the oral bioavailability of this broad-spectrum antibiotic agent. In this study we determined the oral bioavailability of KR-984055 and its prodrugs in the rat, and evaluated the pharmacokinetic model that best describes the plasma concentration behavior following single intravenous (IV) and oral single dose. In addition, concentrations in plasma as well as biliary and urinary recovery of KR-984055 were determined. Also, protein binding of KR-984055 in plasma was examined in vitro. The degree of protein binding of KR-984055 was in the range of 92.09~94.77%. KR-984055 exhibited poor oral bioavailability (7.02$\pm$1.58%). The observed oral bioavailabilities of KR-984055 from KR-999001 and KR-999002 were 38.77$\pm$2.81 % and 39.81$\pm$5.25%, respectively. These data were calculated from the levels of free KR-984055 in plasma. Oral KR-999001 and KR-999002 were not recovered from plasma, suggesting that it was readily cleaved to free KR-984055. KR-999001 and KR-999002 appear to be an efficient oral prod rug of KR-984055 that deserved further clinical evaluation in human.