6, 8 (3) Misclassification of Klatskin tumor as ICC has been shown to result in an overestimation of the incidence of ICC and an underestimation of ECC.10 (4) Most CC studies do not distinguish site (e.g., ductal, hilar, and peripheral) or histology. Specific risk factors for different types of CC are, therefore, likely to be missed, depending on the distribution of these types in a given study. (5) In studies where the distinction between ICC and ECC was used, some potential risk factors seem to have a differential effect on CC, depending on the site. The consistent use of a more refined classification would allow a better understanding of risk factors for CC. CC is a rare malignancy in Western countries, but is more common in

Asia. This difference is mostly attributed to the higher prevalence of established risk factors, such as parasitic infections, bile-duct cysts, and hepatolithiasis. However, most cases of CC are

Nutlin-3 mouse PCI-32765 mw not associated with established risk, except in areas endemic for liver flukes. The established risk factors for CC include parasitic infections, biliary-duct cysts, hepatolithiasis, and PSC. Less-established risk factors include IBD, HCV, HBV, cirrhosis, obesity, diabetes, alcohol, smoking, and genetic polymorphisms. There are not enough consistent data to support that IBD independent of PSC, obesity, smoking, or specific genetic polymorphisms confer an increased risk for CC. Available data suggest that diabetes and heavy alcohol drinking may confer an increased risk for CC. The data also suggest that in Western countries, HCV is consistently associated with ICC and not ECC. In Asian countries, it appears that HBV may be associated with ICC. Cirrhosis is the most consistently illustrated risk factor for ICC, but not ECC. The lack of an accurate, consistent CC classification system may have hindered the conduct and interpretation of risk factors in epidemiological studies. “
“Telaprevir administered for 12 weeks in combination with pegylated interferon

(Peg-IFN) and ribavirin (RBV) substantially enhances the rate of sustained virological response (SVR) in patients with chronic genotype 1 hepatitis C virus (HCV) infection.1, 2 Skin rashes and anemia are the two main side effects of telaprevir. In phase II/III clinical trials, telaprevir resulted in rash for 55% of patients who received at least one dose of telaprevir, MCE公司 6% of which had to discontinue treatment because of the severity of the skin condition.3 To date, the mechanism of skin toxicity of telaprevir is unknown. Most of the rash events with telaprevir were classified as grade 1 or 2, but few severe cutaneous adverse reactions (SCARs) have also been reported during phase II and III protocols.3 In case of grade 1 and 2 rash, telaprevir can be continued and the patient should be treated by topical steroids associated with emollients and antihistaminic drugs. A follow-up by a dermatologist is recommended for patients with a grade 2 rash.

Greg recalls that UCSF was an excellent

training venue where residents worked independently and were given significant leadership opportunities early in their careers. Greg successfully completed his residency in Internal Medicine, spent a year as Chief Resident, and then became the Assistant Chief of Medicine. He was recognized at this early stage in his career as being an excellent teacher and mentor for both the house staff and junior faculty, and soon became the Director of the Internal Medicine Residency Training Program. Greg Ulixertinib supplier recalls that during this period, Dr. Lloyd Hollingsworth “Holly” Smith, longtime Chair of Medicine at UCSF, served as a wonderful teacher and role model and provided valuable instruction to the new Program Director: “It’s hard to read the handwriting on the wall when your back is up against it,” Greg recalls Holly saying. Among other mentors, Greg recognizes Dr. Bruce Scharschmidt, Division Chief of GI at the time, as the one who introduced him to a laboratory world that embraced both clinical and research themes. He pursued a research fellowship in Gastroenterology, applying the previous knowledge and techniques gained from his early epilepsy research as a medical student to new and groundbreaking areas exploring hepatobiliary transport. Greg remembers fondly the young and dynamic lab and his colleagues at the time, including Steve Lidofsky

and Jack Lake, all headed by Dr. Bruce Scharschmidt. The http://www.selleckchem.com/products/DAPT-GSI-IX.html group shared “the bunkhouse,” a crammed office space with metal desks side-by-side, where faculty and fellows were treated non-discriminately and hours were

spent in “OFAT” (obligatory fooling around time) to test new and creative hypotheses and experimental ideas. Bruce remembers that Greg would easily transition from performing experiments at his patch clamp rig to leading the residents during clinical rounds. “Greg was always friendly and engaged, and he never appeared stressed” recalls Bruce, “In all my years, he was truly the best example of a triple threat: clinician, researcher, and educator.” The time in San Francisco was an exciting and busy one for both Greg and Linda, especially with the arrival of their two sons, Guy and Thomas. In 1989, Greg returned to Duke as an Associate Professor of Medicine and joined the GI Division, 上海皓元 which was headed by Dr. Ian Taylor at the time. He quickly went to work building his patch clamp rigs, designing electrophysiological experiments, and firmly establishing his research program. He was awarded his first National Institutes of Health (NIH) R01 award at this time, “Mechanisms of Hepatocyte Electrolyte Transport,” a grant he was to renew for more than two decades. This was followed in a few years with his second R01 award, “Regulation of Secretion by Bile Duct Epithelial Cells,” a grant he would also hold, through multiple renewals, for the next 20 years.

6%) of the 10 769 commune health stations which provide health services in Viet Nam found that liver cancer is the most common cause of cancer Selleckchem INCB024360 death in Viet Nam,6 accounting for 27.1% of cancer deaths (31.04% in men and 19.91% in women).

It is thought that over 90% of these liver cancer deaths reflected the high prevalence of HBV infection in Viet Nam.23 Alcohol and HCV infection are other likely contributors to this high rate of liver cancer. In one study of patients diagnosed with HCC, the majority (85%) had evidence of CHB; almost one in seven patients had evidence of HCV.24 For prevention of liver cancer in Viet Nam, the first long-term focus should be HBV vaccination, thus effecting primary prevention of all liver cancers that are related to this virus. In addition, it will be important to use the best available treatments to profoundly suppress HBV and HCV in the chronically infected to lessen HCC risk. It will also be important to address alcoholic liver disease well before it reaches the stage that can

lead to cancer. There are many challenges that exist in Viet Nam related to providing the type of total integrated approach to liver disease that could substantially decrease both morbidity and mortality. Although 70–75% of Viet Nam’s 84 million people dwell in rural and mountainous regions where medical care is substantially limited, almost all of the 10 769 communes have a health center which provides both primary health care and preventive health-care activities,25 a potentially valuable resource for addressing liver disease. Providing the health centers with simple accurate guides on proper screening and vaccination procedures PD-0332991 cell line for HBV, screening MCE for HCV, and treatment for those with CHB and CHC could guide them to proper care of liver disease patients. Because these commune health centers already have information flowing to and from the Ministry of Health, a national mandate to improve liver disease services could efficiently reach the local commune level. It will also

be important to enlist private health-care providers as in some areas there are more private providers than public ones.26 The non-profit health organizations that provide health care in Viet Nam are also valuable resources. All provinces and most communes (95.7%) have a Red Cross Society branch that provides free health checks for the poor and other vulnerable groups, including children, the elderly, and women,25 so enlisting their help in the campaign against liver disease might be invaluable. Re-use of contaminated needles, syringes, and inadequately sterilized medical equipment is another major challenge that must be addressed. Recent Vietnamese studies have identified as major risk factors for HBV infection a history of hospitalization and of acupuncture4 as well as a history of surgery.9 HCV prevalence is particularly high in patients on maintenance hemodialysis (54%) and those with hemophilia (29%).

6 years (range 19–78 years), 63% were male and 37% were HBeAg positive at baseline. Responses to treatment in both groups are shown in Table 1. Table 1: Responses to entecavir in patients with cirrhosis and without cirrhosis   No Cirrhosis (n = 70) Cirrhosis

(n = 30) p value BASELINE Age, years 45.7 ± 13.2 48.8 ± 14.6 Selleckchem Opaganib 0.3029 Gender, M : F 40:30 23:7 0.0740 Positive HBeAg, n (%) 25 (36) 12 (40) 0.8215 Viral load, log10 IU/ml 5.30 ± 2.08 5.49 ± 1.84 0.6976 ALT, U/L 119 149 0.7528 eGFR, mL/min/1.73 m∧2 95.98 94.88 0.8307 AT 12 MONTHS Viral load, mean log10 IU/ml 2.03 ± 0.71 2.03 ± 1.25 0.9791 2 log drop from baseline, n/total (%) 36/36 (100) 13/14 (93) 0.2800 Viral load <1.73 log10 IU/ml, n/total (%) 35/51 (69) 13/23 (59) 0.4305 ALT < 35 U/L, n (%) 20/38 (53) 8/24 (33) 0.1915 HBe-Ag seroconversion, n (%) 5/25 (20) 1/12 (8.3) 0.6409 eGFR, mL/min/1.73 m∧2 92.58 88.70 0.5653 Conclusions: Entecavir 0.5 mg daily is an effective treatment in

patients with and without cirrhosis with 98% achieving 2 log10 reduction in viral load and 65% achieving viral load to below limit of quantification after 12 months. There were no significant differences in virological Tyrosine Kinase Inhibitor Library screening and biochemical responses to treatment in both groups. Although HBeAg seroconversion is slightly higher in the group without cirrhosis, the difference was not significant. There was no change in renal function after 12 months treatment with entecavir. ZY NG,1 J KONG,1 N KONTORINIS,1 L TARQUINIO,1 J FLEXMAN,2 W CHENG1 Depts of 1Gastroenterology & Hepatology and 2Microbiology, Royal Perth Hospital, Perth Western Australia Background and Aims: Virological suppression and HBeAg seroconversion are important objectives in the treatment of chronic hepatitis B (CHB) patients. HBeAg seroconversion may enable finite treatment with oral nucleos(t)ide analogues. Duration of therapy in these patients may be influenced by the time for HBeAg seroconversion. The aims of the study are (1) To assess

factors predicting virological suppression in CHB patients after treatment with entecavir for 12 months (2) To determine association 上海皓元医药股份有限公司 between virological suppression and HBeAg seroconversion. Methods: Retrospective study of all CHB patients treated with entecavir 0.5 mg at Royal Perth Hospital between 2007 and 2012. Subjects were identified using pharmacy database for entecavir scripts and data was obtained from electronic database. Data collected included demographics, stage of liver disease, HBeAg status, viral load, ALT and GGT at baseline and during treatment. Virological suppression was defined as suppressed hepatitis B viral load (VL) to < log101.73 IU/ml (lower limit of quantification). T-test was used to compare means and Fischer’s exact test was used to compare between groups with statistical significance determined at p < 0.05. Results: 100 CHB patients were included in the study. Mean age was 46.6 yrs (range 19–78 yrs) with mean length of treatment of 22.8 months.

AUC, area under the curve; CA 19-9, carbohydrate antigen 19-9; CC, cholangiocarcinoma; CEA, carcinoembryonic antigen; CE-MS, capillary electrophoresis mass spectrometry; ERCP, endoscopic retrograde cholangiopancreaticography; LC-MS, liquid chromatography-mass spectrometry; PSC, primary sclerosing cholangitis; PTC, percutaneous transhepatic cholangiographies; ROC, receiver operating TAM Receptor inhibitor characteristic; SDS-PAGE, sodium

dodecylsulfate polyacrylamide gel electrophoresis; SVM, support vector machine. Bile samples were collected at the gastrointestinal endoscopy unit of the Hannover Medical School, Germany. We performed 142 endoscopic procedures and bile aspiration was successful in 75% of cases. From 94 consecutive patients included in the study, bile samples were successfully collected during 107 interventions (102 ERCs, five percutaneous transhepatic cholangiographies [PTC]). Indications for cholangiographic interventions were: PSC, CC, and choledocholithiasis. Ten patients developed CC in addition to PSC. Clinical cholangitis selleck chemical was present preintervention in one patient with choledocholithiasis,

in three patients with PSC, and in two patients with CC. We defined cholangitis as the presence of fever, elevated C-reactive protein (CRP), and alkaline phosphatase (AP). Antibiotic treatment before intervention was initiated in 30 out of 107 endoscopic procedures (seven choledocholithiasis, eight PSC, 15 CC).

We performed microbiological bile analysis in 93/107 examinations and bile remained sterile in only 15% of cases (1/30 choledocholithiasis, 7/36 PSC, 8/41 CC). Coexistent 上海皓元医药股份有限公司 bacterial infection (bacteriobilia with fever, elevated CRP, AP, and gamma-GT) was present in six patients. Detailed patients characteristics and laboratory data are given in Table 1. The diagnosis of PSC was based on typical cholangiographic findings such as strictures or irregularity of intrahepatic or extrahepatic bile ducts after exclusion of secondary causes for sclerosing cholangitis. CC was proven histologically in 35 out of 38 patients. In three patients a definite histology could not be obtained, but clinical, laboratory, radiological, and ERCP findings were consistent with a diagnosis of CC. None of the patients with CC received chemotherapy before the cholangiographic intervention. The diagnosis of choledocholithiasis was based on ultrasound and/or endoscopic ultrasound and confirmed by ERC. The trial was approved by the local ethical committee of Hannover Medical School and written informed consent was obtained from all patients. Bile collection was performed as previously described.21 In brief, bile was aspirated by placing a 5F standard ERC catheter (without previous flushing) into the bile duct before contrast dye injection. Approximately 0.5 to 6 mL of bile (mean 2 mL) were collected and transferred into a sterile tube.

Our aim was to examine whether the dysregulated sumoylation could regulate the ethanol-induced CYP2E1 expression in ALD and elucidate the molecular mechanism(s). Methods: Studies were done using in vivo binge ethanol-fed mice, primary mouse hepatocytes in matrigel. Gene and protein expression

were measured by real-time PCR and Western blot analyses, respectively. Promoter activity, Chromatin Immunoprecipitation (Chip) assay and in vitro protein sumoylation were analyzed using commercial kits. Results: We found Ubc9 mRNA level is increased in the livers of binge mice and ethanol-treated hepatocytes whereas CYP2E1 mRNA levels increased minimally. In contrast, protein levels of Ubc9 and CYP2E1 are both induced. Ubc9 knockdown reduced CYP2E1 mRNA level and CYP2E1 promoter activity. Cabozantinib cell line Chip assay showed that Ubc9 is required for NF-κB and C/EBPp, two positive regulators of CYP2E1 promoter activity known to be sumoylated, to interact with CYP2E1 promoter in hepatocytes. In addition, silencing Ubc9 prevented ethanol-mediated induction in CYP2E1 protein level when de novo mRNA synthesis is blocked by actinomycin D, suggesting that most of the increase in CYP2E1 protein level

was at the translational level and this required Ubc9. Finally, we found that CYP2E1 is sumoylated in vitro and in vivo in binge mice livers and increased following ethanol treatment. Conclusions: Ethanol-mediated 上海皓元医药股份有限公司 sumoylation selleck inhibitor increased CYP2E1 expression in livers of binge mice and primary hepatocytes. Sumoylation positively regulates CYP2E1 promoter activity but the primary role of sumoylation

is to stabilize CYP2E1 protein after ethanol treatment. To our knowledge, this is the first report of ethanol-mediated up-regulation of CYP2E1 via sumoylation induction, leading to increased CYP2E1 protein stability. Disclosures: The following people have nothing to disclose: Maria Lauda Tomasi, Minjung Ryoo, Diana Arsene Background. Vinyl chloride (VC) is a ubiquitous environmental contaminant and ranks 4th on the ATSDR Hazardous Substances Priority List. We have previously reported increased hepatocellular necrosis in a highly exposed occupational cohort and in vitro models. A major paradigm shift in environmental research is to assess the impact of underlying disorders that may modify risk. Arguably, the most ubiquitous underlying disorder in the developed world is obesity. The impact of obesity and obesity-induced liver damage (i.e., NAFLD) on hepatic injury caused by VC is not known. The purpose of the current study was therefore to investigate hepatic injury caused by chloroethanol (ClEtOH; VC metabolite) in an experimental model of high-fat diet (HFD) induced obesity. Methods. Mice were administered a bolus dose of chloroethanol (or vehicle) 10 wks after being fed an HFD (42% milk fat)-fed or low fat control diet (LFD; 13% milk fat).

Median times to partial success were similar between primary and rescue ITI cohorts in the G-ITI study, with about one-third of patients receiving ITI therapy for >3 years. In summary, data from the G-ITI study (41 cases of primary ITI, 19 cases of rescue

ITI) have demonstrated success rates (complete and partial) of 87% and 74% in primary and rescue ITI, respectively, with 85% of poor prognosis patients achieving success. G-ITI is the largest international multicentre ITI study using a single pdFVIII/VWF product. Response rates in children and adults undergoing primary or rescue ITI therapy, and in patients with risk factors for poor ITI response, are highly encouraging. A peak titre >200 BU mL−1 and a titre >50 BU mL−1 at the start of treatment were clearly negatively related to outcome, whereas age at start of ITI and Lumacaftor chemical structure time between diagnosis of inhibitor and start of ITI were not associated with outcome. S. K. AUSTIN E-mail: [email protected] International consensus guidelines state that

“Factor VIII/VWF concentrates are currently recommended for second-line and salvage ITI in patients who have failed previous attempts at tolerization using monoclonal or recombinant FVIII products” [13, 15]. In addition to these consensus guidelines, there is a growing wealth of scientific and clinical data to support the international consensus guideline statement. It is well established that 20–30% of patients with severe haemophilia who receive on-demand or prophylactic FVIII treatment will develop inhibitors. These patients Selleck PS341 can be offered 上海皓元 ITI therapy

with the aim of becoming tolerized and returning to FVIII prophylaxis. In reality, however, some patients fail to tolerize and should be considered for tolerization with an alternative FVIII product, a strategy known as rescue ITI. With regard to rescue ITI, it is important to understand the definitions of success and failure. Current consensus defines ITI success as restoration of normal pharmacokinetic parameters, including an expected FVIII recovery >66%, an expected elimination half-life (t½) ≥6 h [11] or ≥7 h [11, 16, 17], or, a measurable FVIII trough level after 48 h with a 50 IU kg−1 dose [17]. Partial response can be classified as a stable and good clinical response to FVIII without an anamnestic rise in inhibitor titres but with abnormal pharmacokinetic parameters [11, 17]. Failure can be defined as the failure to achieve tolerization within 33 months or, more specifically, failure to achieve a 20% reduction in inhibitor titre over any 6-month period after the first 3 months [11, 16-18]. If the success of ITI is classified in this manner, patients demonstrating success are theoretically handling their FVIII normally.

293T cells were transfected Selleck Ulixertinib with either FLAG-SV1 or FLAG-KLF6. Coimmunoprecipitation using α-FLAG beads, followed by immunoblotting with a KLF6 polyclonal antibody that detects both KLF6 and SV1 protein, was performed. In the cells transfected with FLAG-SV1, endogenous KLF6 was recovered and, conversely, in

the cells transfected with FLAG-KLF6 SV1 was recovered, documenting physical interaction between SV1 and KLF6 (Fig. 6). To date, Ras-induced SV1 has been shown to decrease KLF6 promoter occupancy.16, 22 We confirmed the antagonistic function of SV1 to KLF6 by assessing the impact of SV1 on the transcriptional activity of KLF6 in cell culture using the p21 promoter, a well-validated direct transcriptional target of KLF6.5 In both 293T (Fig. 7A), and HUH7 cells DAPT ic50 (Fig. 7B), transfection of FLAG-SV1 alone did not affect p21 activity, whereas cotransfection of FLAG-SV1 with FLAG-KLF6 significantly reduced the increase in p21-luciferase activity induced by FLAG-KLF6 alone (P < 0.05). Similar to

transfected cells, p21 protein levels were decreased in primary hepatocytes from our AlbCre Klf6fl(+/+)- and SV1 AlbCre Klf6fl(+/+) mice in comparison with the Klf6fl(+/+) hepatocytes with endogenous Klf6 (Fig. 7C). Moreover, in primary hepatocytes from Klf6fl(+/+) mice transduced with either AdenoCre virus or pBabe- or pBabeSV1 lentivirus, respectively, Klf6 depletion was also associated with a decrease in p21 protein levels (Fig. 7D). These findings confirm p21 as a transcriptional target of KLF6 and establish a bona fide antagonistic function of SV1. Because SV1 is localized primarily in the cytoplasm26 and can interact with KLF6, we hypothesized that SV1 antagonizes KLF6 by accelerating its degradation in the cytoplasm. To test this hypothesis, increasing amounts of FLAG-SV1 MCE公司 cDNA were cotransfected with a constant amount of FLAG-KLF6. This led to an SV1-dependent decrease in KLF6 protein in both

293T (Fig. 8A), and HUH7 cells (Fig. 8C), without affecting KLF6 RNA levels (not shown), which was quantified in four 293T immunoblots (Fig. 8B, P < 0.05). To assess if decreased KLF6 protein was due to accelerated degradation of KLF6, 293T cells were cotransfected with either pCI-neo-GFP+FLAG-KLF6 or FLAG-SV1+FLAG-KLF6, and protein was collected 24 hours after transfection and at 0, 15, 30, and 60 minutes after adding cycloheximide (Fig. 8D,E). In the presence of SV1, KLF6 protein levels at baseline were significantly lower (Fig. 8E, P < 0.05) and KLF6 degradation was accelerated 60 minutes after adding cycloheximide (Fig. 8E, P < 0.005). The accelerated degradation was inhibited by adding the proteasomal inhibitor MG132 (Fig. 8D,F), indicating that SV1 accelerates the proteasomal degradation of KLF6.

21 Importantly, marked bile ductular reaction (Fig. 8) with atypia adjacent to HCC due to mass effect is not an uncommon finding and one should be cautious not click here to overinterpret these atypical ductules as the CC component of the combined HCC-CC. Unfortunately, immunohistochemistry is of little value in distinguishing malignant biliary epithelium from reacting ductules. In general, ductular reaction is often accompanied by inflammatory cell infiltrate, whereas the cholangiocarcinoma component is typically surrounded by a desmoplastic stroma

that lacks inflammatory cells. Despite intensive preoperative imaging studies, many combined HCC-CC may be misdiagnosed either as HCC or CC before surgery. Tissue sampling is always an issue and may preclude an accurate diagnosis in a core needle biopsy specimen. Accurate preoperative diagnosis Ipilimumab purchase is important because the decision on

the most appropriate treatment may depend on the predominant component of the tumor (HCC or CC); however most patients with combined HCC-CC are seldom diagnosed before surgery. This may largely be attributed to the specimen sampled and unless the interface area is biopsied, a confident diagnosis of combined HCC-CC may not be reached. Detection and treatment option may be optimized with advanced imaging studies, high index of suspicion, serum tumor markers (alpha-fetoprotein,

carbohydrate MCE公司 antigen 19-9), and histopathology with appropriate use of immunohistochemistry.36 Recent studies reported that the survival rate of patients with combined HCC-CC after liver resection was poorer than that of patients with HCC or CC37 and pathologically combined HCC-CC showed more significantly vascular invasion and lymph node metastasis than HCC, with a similarity to CC.22 These results are similar to those that were previously reported,38,39 suggesting that a more aggressive treatment modality, such as postoperative adjuvant therapy and multimodality treatment for recurrent disease, may have to be explored to improve the survival rate of these patients. There are very few outcome data on liver transplantation and the role of liver transplantation in combined HCC-CC needs to be defined.40 This is largely hindered by the lack of accurate preoperative diagnosis of combined HCC-CC. Further studies are also warranted to seek optimal therapeutic options in treating combined HCC-CC.41 In addition, in the recently published American Joint Committee on Cancer manual,42 combined HCC-CC is included in the section on Carcinoma of the Intrahepatic Bile Ducts.

21 Importantly, marked bile ductular reaction (Fig. 8) with atypia adjacent to HCC due to mass effect is not an uncommon finding and one should be cautious not RAD001 clinical trial to overinterpret these atypical ductules as the CC component of the combined HCC-CC. Unfortunately, immunohistochemistry is of little value in distinguishing malignant biliary epithelium from reacting ductules. In general, ductular reaction is often accompanied by inflammatory cell infiltrate, whereas the cholangiocarcinoma component is typically surrounded by a desmoplastic stroma

that lacks inflammatory cells. Despite intensive preoperative imaging studies, many combined HCC-CC may be misdiagnosed either as HCC or CC before surgery. Tissue sampling is always an issue and may preclude an accurate diagnosis in a core needle biopsy specimen. Accurate preoperative diagnosis FK506 is important because the decision on

the most appropriate treatment may depend on the predominant component of the tumor (HCC or CC); however most patients with combined HCC-CC are seldom diagnosed before surgery. This may largely be attributed to the specimen sampled and unless the interface area is biopsied, a confident diagnosis of combined HCC-CC may not be reached. Detection and treatment option may be optimized with advanced imaging studies, high index of suspicion, serum tumor markers (alpha-fetoprotein,

carbohydrate medchemexpress antigen 19-9), and histopathology with appropriate use of immunohistochemistry.36 Recent studies reported that the survival rate of patients with combined HCC-CC after liver resection was poorer than that of patients with HCC or CC37 and pathologically combined HCC-CC showed more significantly vascular invasion and lymph node metastasis than HCC, with a similarity to CC.22 These results are similar to those that were previously reported,38,39 suggesting that a more aggressive treatment modality, such as postoperative adjuvant therapy and multimodality treatment for recurrent disease, may have to be explored to improve the survival rate of these patients. There are very few outcome data on liver transplantation and the role of liver transplantation in combined HCC-CC needs to be defined.40 This is largely hindered by the lack of accurate preoperative diagnosis of combined HCC-CC. Further studies are also warranted to seek optimal therapeutic options in treating combined HCC-CC.41 In addition, in the recently published American Joint Committee on Cancer manual,42 combined HCC-CC is included in the section on Carcinoma of the Intrahepatic Bile Ducts.