• Asian Pacific Journal of Cancer Prevention
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• v.17 no.8
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• pp.4155-4161
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• 2016

Biliary obstruction is a common clinical manifestation of various conditions, including extrahepatic cholangiocarcinoma. However, a screening test for diagnosis of extrahepatic cholangiocarcinoma in patients with biliary obstruction is not yet available. According to the rationale that the biliary system plays a major role in lipid metabolism, biliary obstruction may interfere with lipid profiles in the body. Therefore, plasma lipidomics may help indicate the presence or status of disease in biliary obstruction suspected extrahepatic cholangiocarcinoma. This study aimed to use plasma lipidomics for diagnosis of extrahepatic cholangiocarcinoma in patients with biliary obstruction. Plasma from healthy volunteers, patients with benign biliary obstruction extrahepatic cholangiocarcinoma, and other related cancers were used in this study. Plasma lipids were extracted and lipidomic analysis was performed using matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Lipid profiles from extrahepatic cholangiocarcinoma patients showed significant differences from both normal and benign biliary obstruction conditions, with no distinction between the latter two. Relative intensity of the selected lipid mass was able to successfully differentiate all extrahepatic cholangiocarcinoma samples from patient samples taken from healthy volunteers, patients with benign biliary obstruction, and patients with other related cancers. In conclusion, lipidomics is a non-invasive method with high sensitivity and specificity for identification of extrahepatic cholangiocarcinoma in patients with biliary obstruction.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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• pp.321-324
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• 2013

Background: Intra- and extrahepatic cholangiocarcinoma (CCA) is the most common cancer in Thailand, especially in the northeast region. Most extrahepatic CCA patients consult a doctor at a late stage. Surgery is still the best treatment. Objectives: The aim of this study was to evaluate survival rates and factors affecting survival in extrahepatic CCA patients following surgery at Srinagarind Hospital, Khon Kaen University, Thailand. Materials and Methods: A retrospective cohort study was conducted with 58 patients who were diagnosed and treated by surgical resection by the same surgeon at Srinagarind Hospital between 2005 and 2009. The patients were followed up until death or the end of the study (31 December, 2011). Survival rates were calculated by the Kaplan-Meier method, and the Cox proportional hazard model was used to identify independent prognostic factors. Results: The total follow-up time was 1,215 person-months, and the mortality rate was 50 per 100 person-years. The cumulative 1-, 3-, and 5-year survival rates were 62.1%, 21.7% and 10.8%, respectively. The median survival time after resection was 15 months. After adjusting for age, gender, lymph node metastasis and histological type, resection margin remained as a statistically significant prognostic factor for survival following surgery. A positive resection margin was associated with a 2.3-fold higher mortality rate than a negative margin. Conclusions: Resection margins are important prognostic factors affecting survival of extrahepatic CCA patients after surgery. A negative resection margin can reduce the mortality rate by 56%.

• Journal of the Korean Society of Radiology
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• v.82 no.4
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• pp.964-970
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• 2021

Extrahepatic duct duplication is an extremely rare congenital anomaly. Hilar cholangiocarcinoma with extrahepatic bile duct duplication was reported; however, intraductal papillary neoplasm of the bile duct (IPNB) with extrahepatic bile duct duplication has not been reported to the best of our knowledge. We report a rare case of IPNB with extrahepatic bile duct duplication of a 64-year-old female. The patient underwent extended right hepatectomy, and the results of a subsequence histopathological examination were consistent with an IPNB with extrahepatic bile duct duplication. We report this rare case with radiologic imaging findings and a brief review of the current literature.

• Molecules and Cells
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• v.40 no.5
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• pp.363-370
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• 2017

Extrahepatic cholangiocarcinoma (ECC), a malignant tumor of biliary origin, has a poor prognosis with limited treatment options. The KRAS oncogene is the most commonly mutated gene in ECC and one of the factors that predicts a poor prognosis and low survival rate. L1 cell adhesion molecule (L1CAM) is expressed in ECC cells and acts as an independent poor prognostic factor in predicting patient survival. In this study we investigate the functional significance of L1CAM in ECC cells with activating KRAS mutation. We selected an ECC cell line, EGI-1, with activating KRAS mutation, and then confirmed its expression of L1CAM by RT-PCR, western blot analysis, and flow cytometry. The suppression of L1CAM expression (using a specific lentivirus-delivered shRNA) significantly decreased the migratory and invasive properties of EGI-1 cells, without altering their proliferation or survival. Analyses of signaling effectors in L1CAM-depleted and control EGI-1 cells indicated that L1CAM suppression decreased the levels of both phosphorylated MKK4 and total MKK4, together with c-Jun N-terminal kinase (JNK) phosphorylation. Further, exposure to a JNK inhibitor (SP600125) decreased migration and invasion of EGI-1 cells. These results suggest that L1CAM promotes cellular migration and invasion via the induction of MKK4 expression, leading to JNK activation. Our study is the first to demonstrate a functional role for L1CAM in ECC carrying the activating KRAS mutation. Given that KRAS is the most commonly mutated oncogene in ECC, L1CAM may serve as an attractive therapeutic target for ECC cells with activating KRAS mutation.

• Journal of Digestive Cancer Research
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• v.2 no.1
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• pp.32-36
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• 2014

We report a patient with combined hepatocellular-cholangiocarcinoma confined in the common hepatic duct and scirrhous type of hepatocellular carcinoma in the caudate lobe of liver simultaneously. The patient was a 55-yearsold Korean man with hepatitis B virus (HBV) carrier who was referred from a local hospital due to detected liver mass on abdominal computed tomography (CT). He has presented jaundice and weight loss for the previous 3 weeks. Laboratory examination showed AST/ALT elevation and hyperbilirubinemia. HBsAg was positive. The tumor marker study showed elevated AFP and DCP, not CEA and CA 19-9. Abdominal CT disclosed an about 2.1×0.9 cm sized soft tissue density in hilum with both intrahepatic duct (IHD) dilatations and an about 3×2.1 cm sized arterial enhancing lesion at segment 8 of the liver. Patient received 15 cycles of Gemcitabine/Cisplantin chemotherapy from February 27, 2013 to December 31, 2013. Caudate lobectomy of liver, segmental resection of bile duct and Roux-en-Y hepaticojejunostomy was performed on February 10, 2014. The final pathologic report showed double primary liver cancer, combined hepatocellular-cholangiocarcinoma in common hepatic bile duct and scirrhous type of hepatocellular carcinoma in segment 1 of the liver. This is a very unusual case in which combined hepatocellular-cholangiocarcinoma confined in the large bile duct and two rare hepatic cancers coexisted.

• Parasites, Hosts and Diseases
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• v.57 no.5
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• pp.517-520
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• 2019

Echinococcosis is a disease caused by the Echinococcus species that parasitizes in humans. Alveolar echinococcosis (AE) which is caused by Echinococcus multilocularis is harmful to humans. AE mainly occurs in the liver and can be transferred to retroperitoneal lymph nodes, lung, brain, bone, spleen and other organs through lymphatic and blood vessels. Cholangiocarcinoma can occur in of the intrahepatic and extrahepatic bile ducts and is more common in the hilar. We reported a case of hilar bile duct alveolar echinococcosis which was originally misdiagnosed an cholangiocarcinoma.

• Korean Journal of Radiology
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• v.24 no.10
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• pp.983-995
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• 2023

Objective: To compare the diagnostic performance and interobserver agreement between contrast-enhanced computed tomography (CECT) and contrast-enhanced magnetic resonance imaging (CE-MRI) with magnetic resonance cholangiopancreatography (MRCP) for evaluating the resectability in patients with extrahepatic cholangiocarcinoma (eCCA). Materials and Methods: This retrospective study included treatment-naïve patients with pathologically confirmed eCCA, who underwent both CECT and CE-MRI with MRCP using extracellular contrast media between January 2015 and December 2020. Among the 214 patients (146 males; mean age ± standard deviation, 68 ± 9 years) included, 121 (56.5%) had perihilar cholangiocarcinoma. R0 resection was achieved in 108 of the 153 (70.6%) patients who underwent curative-intent surgery. Four fellowship-trained radiologists independently reviewed the findings of both CECT and CE-MRI with MRCP to assess the local tumor extent and distant metastasis for determining resectability. The pooled area under the receiver operating characteristic curve (AUC), sensitivity, and specificity of CECT and CE-MRI with MRCP were compared using clinical, surgical, and pathological findings as reference standards. The interobserver agreement of resectability was evaluated using Fleiss kappa (κ). Results: No significant differences were observed between CECT and CE-MRI with MRCP in the pooled AUC (0.753 vs. 0.767), sensitivity (84.7% [366/432] vs. 90.3% [390/432]), and specificity (52.6% [223/424] vs. 51.4% [218/424]) (P > 0.05 for all). The AUC for determining resectability was higher when CECT and CE-MRI with MRCP were reviewed together than when CECT was reviewed alone in patients with discrepancies between the imaging modalities or with indeterminate resectability (0.798 [0.754-0.841] vs. 0.753 [0.697-0.808], P = 0.014). The interobserver agreement for overall resectability was fair for both CECT (κ = 0.323) and CE-MRI with MRCP (κ = 0.320), without a significant difference (P = 0.884). Conclusion: CECT and CE-MRI with MRCP showed no significant differences in the diagnostic performance and interobserver agreement in determining the resectability in patients with eCCA.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.5
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• pp.2099-2102
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• 2015

Objective: To explore the expression of $laminin{\gamma}2$ in extrahepatic cholangiocarcinoma (EHCC) tissues and its influence on tumor invasion and metastasis. Materials and Methods: Paraffin embedding samples of cancer, para-cancer, lymph node metastatic and hepatic metastatic tissues from 79 patients undergoing EHCC resection were collected. Expression of $laminin{\gamma}2$ was detected by immunohistochemistry and its relationship with clinical pathological characteristics and the prognosis of EHCC patients were analyzed. Results: $Laminin{\gamma}2$ showed negative staining in para-cancer tissues, but demonstrated a 51.9% (41/79) positive expression rate in extracellular matrix (ECM) or cytoplasm of EHCC tissues. In lymph node metastatic and distant metastatic nidi, expression of $laminin{\gamma}2$ was significantly higher than in the primary nidi (${\chi}^2=7.4173$, P=0.0065; ${\chi}^2=4.0077$, P=0.0453). The expression was in obvious association with lymph node metastasis (P<0.01), but had no relevance with age, gender, tumor location, tumor stage, differentiation and distant metastasis in ECM (P>0.05), whereas it was in marked connection with lymph node and distant metastasis (P<0.05 or P<0.01), but had no relationship with age, gender, tumor location, tumor stage and differentiation in cytoplasm (P>0.05). However, the median survival time and median recurrent period of patients with positive expression of $laminin{\gamma}2$ in both cytoplasm and ECM of tumor cells, only in ECM and only in cytoplasm, were evidently lower than with negative expression of $laminin{\gamma}2$ in RCM and cytoplasm (P<0.05 or P<0.01). Further Cox regression analysis showed that the positive expression of $laminin{\gamma}2$ and the tumor differentiation were independent risk factors influencing the prognosis of EHCC patients. Conclusions: Abnormal expression of $laminin{\gamma}2$ may be closely associated with invasion and metastasis of tumor cells, and thus a potential molecular marker for prognosis of EHCC patients.

• Journal of Yeungnam Medical Science
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• v.33 no.2
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• pp.77-84
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• 2016

Pancreatic cancer, the 4th leading cause of cancer-related death in the United States, has a very poor prognosis. Cholangiocarcinoma originates from either intrahepatic or extrahepatic bile duct, and its incidence is gradually increasing worldwide. Endoscopic retrograde cholangiopancreatography with brush cytology has a high false-negative rate for the diagnosis of biliary malignancy. Recently, endoscopic ultrasonography (EUS) has emerged as the potential modality to detect pancreatic cancer. EUS-guided fine needle aspiration for cytologic analysis made it possible to overcome the obstacle in differentiating between benign and malignant lesions in the pancreatobiliary lesion, and it has been well established as a safe and effective procedure. Herein, the clinical application of EUS in the diagnosis of pancreatobiliary cancer was reviewed.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.7
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• pp.3043-3050
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• 2015

The tumor microenvironment (TME) includes numerous non-neoplastic cells such as leukocytes and fibroblasts that surround the neoplasm and influence its growth. Tumor-associated macrophages (TAMs) and cancerassociated fibroblasts (CAFs) are documented as key players in facilitating cancer appearance and progression. Alteration of the macrophage (CD68, CD163) and fibroblast (${\alpha}-SMA$, FSP-1) cells in Opisthorchis viverrini (Ov) -induced cholangiocarcinoma (CCA) was here assessed using liver tissues from an established hamster model and from 43 human cases using immunohistochemistry. We further investigated whether M2-activated TAMs influence CCA cell migration ability by wound healing assay and Western blot analysis. Macrophages and fibroblasts change their phenotypes to M2-TAMs (CD68+, CD163+) and CAFs (${\alpha}-SMA+$, FSP-1+), respectively in the early stages of carcinogenesis. Interestingly, a high density of the M2-TAMs CCA in patients is significantly associated with the presence of extrahepatic metastases (p=0.021). Similarly, CD163+ CCA cells are correlated with metastases (p=0.002), and they may be representative of an epithelial-to-mesenchymal transition (EMT) with increased metastatic activity. We further showed that M2-TAM conditioned medium can induce CCA cell migration as well as increase N-cadherin expression (mesenchymal marker). The present work revealed that significant TME changes occur at an early stage of Ov-induced carcinogenesis and that M2-TAMs are key factors contributing to CCA metastasis, possibly via EMT processes.