Increasing Incidence and Mortality of Primary Intrahepatic Cholangiocarcinoma in the United States

Patel, Tushar

doi:10.1053/jhep.2001.25087

Cited by 944 publications

(664 citation statements)

References 22 publications

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“…The incidence of intrahepatic cholangiocarcinoma is even lower as it accounts for less than 10% of all cholangiocarcinomas, 1 although some recent studies have showed its increasing incidence in the West. 2,3 Complete surgical resection is the only treatment that offers the possibility of long-term survival in patients with intrahepatic cholangiocarcinoma. However, the number of candidates who can undergo curative surgery is limited, because a significant proportion of patients present with advanced disease.…”

mentioning

confidence: 99%

The expression of phospho-AKT1 and phospho-MTOR is associated with a favorable prognosis independent of PTEN expression in intrahepatic cholangiocarcinomas

Lee

Choi

et al. 2012

Modern Pathology

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AKT1 signaling pathway is important for the regulation of protein synthesis and cell survival with implications in carcinogenesis. In this study, we explored the prognostic significance of AKT1 pathway in intrahepatic cholangiocarcinomas. We investigated the status of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), phosphorylated (p) AKT1 (p-AKT1), p-mammalian target of rapamycin (p-MTOR), p-p70 ribosomal protein S6 kinase (p-RPS6KB2) and p-eukaryotic initiation factor 4E-binding protein-1 (p-EIF4EBP1) in 101 intrahepatic cholangiocarcinomas by immunohistochemistry. Western blot analysis was performed to verify the expression levels of p-AKT1 and p-MTOR. The relationship of protein expression with clinicopathological data and the correlations of protein expression levels were explored. The overexpression of p-AKT1, p-MTOR, and PTEN was associated with a better survival in patients with intrahepatic cholangiocarcinoma (P ¼ 0.0137, 0.0194, and 0.0337, respectively). In a multivariate analysis, PTEN was an independent prognostic factor, and p-AKT1 showed tendency (P ¼ 0.032 and 0.051, respectively). The overexpression of p-MTOR was correlated with well-to-moderately differentiated tumors (Po0.001) and tumors without metastasis (P ¼ 0.046). Expression levels of the AKT1 signaling pathway proteins in this study showed positive correlations with each other, except for PTEN. Aberrant expressions of p-AKT1 and p-MTOR in intrahepatic cholangiocarcinoma were associated with a favorable prognosis, possibly in a PTEN-independent manner. Our results indicate that dysregulation of the AKT1 pathway may have an important role in the development of intrahepatic cholangiocarcinoma, but not necessarily in the progression of the disease.

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confidence: 99%

The expression of phospho-AKT1 and phospho-MTOR is associated with a favorable prognosis independent of PTEN expression in intrahepatic cholangiocarcinomas

Lee

Choi

et al. 2012

Modern Pathology

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“…The incidence of ICC has been increasing worldwide over the last several years 3, 4, 5, 6. Surgery is the only hope of achieving a cure in ICC.…”

Section: Intrahepatic Cholangiocarcinomamentioning

confidence: 99%

“…However, surgical results of hepatectomy for liver metastasis have not been fully justified. Kurosaki et al38 reported 13 patients with bile duct cancer7 and ampullary cancer6 who underwent hepatectomy for hepatic recurrence after initial pancreaticoduodenectomy. In their series, four of the 13 cases survived more than 5 years.…”

Section: Extrahepatic Bile Duct Cancermentioning

confidence: 99%

Clinical implication of surgical resection for recurrent biliary tract cancer: Does it work or not?

Miyazaki

Shimizu

Yoshitomi

et al. 2017

Annals of Gastroent Surgery

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Although recent advances in imaging diagnosis, surgical techniques, and perioperative management can result in increased resectability and improved surgical outcomes, most resected patients still develop cancer recurrence. If patients develop cancer recurrence, their prognosis is very ominous. However, there have been some recent reports to show promising outcomes by aggressive surgical strategy in selected patients who developed cancer recurrence. Because there are various surgical procedures being selected at initial surgery in patients with biliary tract cancers, recurrent patterns after resection are very variable in each patient. However, surgical procedures might usually be very complicated and difficult if re‐surgical resection is considered in patients with recurrent biliary tract cancer, Therefore, surgical re‐resection could bring about high surgical morbidity and mortality rates in most previously reported series. Although re‐surgical resection might offer a chance of favorable outcome in selected patients with biliary tract cancers, these aggressive surgical approaches should be carried out in strictly selected patients by expert surgeons at high‐volume centers.

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“…It is now well established that oxysterols are closely associated with the genesis of atherosclerosis [3][4][5] and most probably with various forms of cancer [6][7][8]. Cancer of the biliary system has recently shown an alarming upsurge in incidence and mortality in both the UK and US [9,10] in addition to continuing increases in countries with already high incidence, such as Japan [11]. Little is known of the etiology of cholangiocarcinoma and gallbladder cancer.…”

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confidence: 99%

The production of oxysterols in bile by activated human leukocytes

Haigh

Wong

Lee

2006

Biochemical and Biophysical Research Communications

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Oxysterols are naturally occurring intermediates in the conversion of cholesterol to bile acids, the major route for elimination of cholesterol. Additionally, they are important signaling agents, particularly in control of cholesterol synthesis; however, some species also are cytotoxic and carcinogenic. Oxysterols in plasma, contained in oxidized low-density lipoprotein, are strongly correlated with atherosclerosis. Oxysterols are found in infected human bile and the oxysterol content in gallstones correlates with bacterial DNA in the stones. Here we demonstrate that human leukocytes, activated by the presence of bacterial lipopolysaccharide, are able to oxidize cholesterol to a variety of oxysterols, including species known to be carcinogenic. The occurrence of oxidized forms of cholesterol (oxysterols) in living tissues has now been known for more than six decades [1] and these compounds have been associated with atherogenicity for forty years [2]. It is now well established that oxysterols are closely associated with the genesis of atherosclerosis [3][4][5] and most probably with various forms of cancer [6][7][8]. Cancer of the biliary system has recently shown an alarming upsurge in incidence and mortality in both the UK and US [9,10] in addition to continuing increases in countries with already high incidence, such as Japan [11]. Little is known of the etiology of cholangiocarcinoma and gallbladder cancer. However, we have shown that bacterial infection is involved in the pathogenesis of mixed cholesterol stones and brown pigment stones [12] and that the content of oxysterols is negatively correlated with the cholesterol content of gallstones [13]. We have demonstrated the presence of bacteria in gallstones [12] and of oxysterols in human gallstones and bile [13]. We also have shown that hepatic bile from patients with biliary infection contains significantly higher levels of oxysterols than does such bile from patients lacking infection of the biliary system [18]. We hypothesize that the oxidation of cholesterol in bile occurs as a result of the action of activated leukocytes on invading bacteria. Here we demonstrate that the incubation of activated human peripheral leukocytes with normal human bile, or with model bile, can result in the production of a wide range of oxysterols. Keywords Materials and methods Model bileModel bile was made by dissolving 108 mg of sodium taurocholate (Calbiochem, La Jolla, CA) in 10 ml of methanol and adding 38 mg of phosphatidylcholine (Type XVIE, Sigma, St. Louis, MO). Ten milligrams of three-times recrystallized cholesterol was added with suffcient chloroform to dissolve all components with gentle warming. The solvent was removed on a rotary evaporator at 40 °C, the flask filled with argon, sealed, and stored at -70 °C until used. At that time, 10 ml of DMEM (Gibco, Grand Island, NY) was added with warming to make a clear solution. LeukocytesOne hundred milliliters of blood, drawn from volunteers, was mixed with 100 ml Hanks" BSS (Mediatech, Fisher Scientific, Los...

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Increasing Incidence and Mortality of Primary Intrahepatic Cholangiocarcinoma in the United States

Cited by 944 publications

References 22 publications

The expression of phospho-AKT1 and phospho-MTOR is associated with a favorable prognosis independent of PTEN expression in intrahepatic cholangiocarcinomas

The expression of phospho-AKT1 and phospho-MTOR is associated with a favorable prognosis independent of PTEN expression in intrahepatic cholangiocarcinomas

Clinical implication of surgical resection for recurrent biliary tract cancer: Does it work or not?

The production of oxysterols in bile by activated human leukocytes

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