• Journal of Digestive Cancer Research
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• v.2 no.2
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• pp.78-81
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• 2014

Intraductal papillary neoplasm of the bile duct (IPN-B) is a rare disease characterized by multicentric proliferation of adenomatous epithelium within the bile ducts. It has better prognosis because of slow disease progression and high probability of early diagnosis, but also has potential for malignant transformation. Therefore early treatment such as surgical resection has been recommended. There are few reports about nature course of IPN-B without treatment. We report a case of papillary adenoma of intrahepatic duct that transformed into intrahepatic cholangiocarcinoma with 8 years of follow up.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.2
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• pp.725-729
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• 2012

Background: The management of hepatolithiasis combined with intrahepatic cholangicarcinoma (IHHCC) remains a challenge due to poor prognosis. The aim of this study was to summarize our diagnosis and cure experience of IHHCC over the recent 10 years. Methods: From January 1996 to January 2006, 66 patients with IHHCC were reviewed retrospectively. Results: Of the 66 patients, 52 underwent surgical resection (radical resection in 38 and palliative in 14) and 8 patients abdominal exploration, while the other 6 cases received endoscopic retrograde biliary internal drainage and stent implantation. In this series, correct diagnosis of advanced stage was made during operation in 8 cases (8/60, 13.3%) and all of them (underwent unnecessary abdominal exploration, among them the positive rate of CA19-9 was 100%, and the positive rate of CEA was 87.6% (7/8), incidence rate of ascites was 100% and short-term significant weight loss was 100%, with median overall survival of only 4 months. Conclusion: Radical resection is mandatory for IHHCC patient to achieve long-term survival, the CT and MR imaging features of IHHCC being concentric enhancement. Patients with IHHCC have significant higher CA199 and significant higher CEA and short-term significant weight loss and ascites should be considered with advanced stage of IHHCC and unnecessary non-therapeutic laparotomies should be avoided.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.10
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• pp.4735-4739
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• 2016

Background: Intrahepatic cholangiocarcinoma (IHCCA) is an aggressive tumor for which surgical resection is a mainstay of treatment. However, recurrence after resection is common associated with a poor prognosis. Studies regarding recurrence of mass-forming IHCCA are rare; therefore, we investigated the pattern with our dataset. Methods: We retrospectively reviewed the medical and pathological records of 50 mass-forming IHCCA patients who underwent hepatic resection between January 2004 and December 2009 in order to determine the patterns of recurrence and prognosis. All demographic and operative parameters were analyzed for their effects on recurrence-free survival. Results: The median recurrence-free survival time was 188 days (95%CI: 149-299). The respective 1-, 2-, and 3-year recurrence-free survival rates were 16.2% (95%CI: 6.6-29.4), 5.4% (95%CI: 1.0-15.8) and 2.7% (95%CI: 0.2-12.0). There was an equal distribution of recurrence at solitary and multiple sites. Univariate analysis revealed no factors related to recurrence-free survival.Conclusion: The overall survival and recurrence-free survival after surgery for mass-forming IHCCA were found to be very poor. Almost all recurrences were detected within 2 years after surgery. Adjuvant chemotherapy after surgery may add benefit in the affected patients.

• BMB Reports
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• v.56 no.11
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• pp.600-605
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• 2023

Intrahepatic cholangiocarcinoma (ICC) is a bile duct cancer and a rare malignant tumor with a poor prognosis owing to the lack of an early diagnosis and resistance to conventional chemotherapy. A combination of gemcitabine and cisplatin is the typically attempted first-line treatment approach. However, the underlying mechanism of resistance to chemotherapy is poorly understood. We addressed this by studying dynamics in the human ICC SCK cell line. Here, we report that the regulation of glucose and glutamine metabolism was a key factor in overcoming cisplatin resistance in SCK cells. RNA sequencing analysis revealed a high enrichment cell cycle-related gene set score in cisplatin-resistant SCK (SCK-R) cells compared to parental SCK (SCK WT) cells. Cell cycle progression correlates with increased nutrient requirement and cancer proliferation or metastasis. Commonly, cancer cells are dependent upon glucose and glutamine availability for survival and proliferation. Indeed, we observed the increased expression of GLUT (glucose transporter), ASCT2 (glutamine transporter), and cancer progression markers in SCK-R cells. Thus, we inhibited enhanced metabolic reprogramming in SCK-R cells through nutrient starvation. SCK-R cells were sensitized to cisplatin, especially under glucose starvation. Glutaminase-1 (GLS1), which is a mitochondrial enzyme involved in tumorigenesis and progression in cancer cells, was upregulated in SCK-R cells. Targeting GLS1 with the GLS1 inhibitor CB-839 (telaglenastat) effectively reduced the expression of cancer progression markers. Taken together, our study results suggest that a combination of GLUT inhibition, which mimics glucose starvation, and GLS1 inhibition could be a therapeutic strategy to increase the chemosensitivity of ICC.

• Annals of Hepato-Biliary-Pancreatic Surgery
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• v.27 no.2
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• pp.158-165
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• 2023

Backgrounds/Aims: Within two years of surgery, 70% of resected intrahepatic cholangiocarcinoma (iCCA) recur. Better biomarkers are needed to identify those at risk of "early recurrence" (ER). In this study, we defined ER and investigated whether preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic-inflammatory index were prognostic of both overall relapse and ER after curative hepatectomy for iCCA. Methods: A retrospective cohort of patients who underwent curative-intent hepatectomy for iCCA between 2005 and 2017 were created. The cut-off timepoint for the ER of iCCA was estimated using a piecewise linear regression model. Univariable analyses of recurrence were conducted for the overall, early, and late recurrence periods. For the early and late recurrence periods, multivariable Cox regression with time-varying regression coefficient analysis was used. Results: A total of 113 patients were included in this study. ER was defined as recurrence within 12 months of a curative resection. Among the included patients, 38.1% experienced ER. In the univariable model, a higher preoperative NLR (> 4.3) was significantly associated with an increased risk of recurrence overall and in the first 12 months after curative surgery. In the multivariable model, a higher NLR was associated with a higher recurrence rate overall and in the ER period (≤ 12 months), but not in the late recurrence period. Conclusions: Preoperative NLR was prognostic of both overall recurrence and ER after curative iCCA resection. NLR is easily obtained before and after surgery and should be integrated into ER prediction tools to guide preoperative treatments and intensify postoperative follow-up.

• Annals of Hepato-Biliary-Pancreatic Surgery
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• v.26 no.3
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• pp.235-243
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• 2022

Backgrounds/Aims: Historically, the incidence and prognosis of patients diagnosed with intrahepatic cholangiocarcinoma (ICC) have been inadequately understood. Survival analysis in ICC has yet to be investigated in a population-based study. Methods: We conducted a retrospective cohort study using the Surveillance, Epidemiology, and End Results Program (SEER) 18 Registry. Risk ratios were estimated via Poisson regression. Hazard ratios for 5-year survival were estimated using hierarchical Cox regression models. Results: Males show a higher rate of age-adjusted ICC incidence. Blacks carried a decreased risk of ICC diagnosis than Whites, while Asians revealed a higher risk of ICC diagnosis when compared with Whites. The observed survival rates at 12, 36, and 60 months were 36.3%, 12.8%, and 8.1%, respectively. Compared with Whites, Blacks showed an increased risk of death (p < 0.01). Lymph node resection during surgery was associated with a 64.1% reduced risk of mortality (p < 0.01). A higher T stage at diagnosis was associated with poor survival (p < 0.01). Surgery combined with chemoradiotherapy, radiotherapy, or chemotherapy was associated with a reduced risk of mortality compared with nonsurgical interventions (p < 0.01). Conclusions: ICC incidence has been increasing since 2000, especially in White males. The risk of ICC rises with age. Lymph node removal is associated with better survival. In recent years, survival had worsened, and surgical intervention improved survival compared with nonsurgical management.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.7
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• pp.3299-3304
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• 2014

Background: The aim of the present study was to analyze whether Homer1 is a potential prognostic marker for intrahepatic cholangiocarcinoma (ICC). Materials and Methods: The expression of Homer1 in ICC tissue was detected with immunohistochemistry and levels of protein in ICC and paratumor tissues were evaluated by Western blotting. Survival analysis by the Kaplan-Meier method was performed to assess prognostic significance. Results: Homer1 expression was high in 67.4% (58/86) of ICC samples, and there was significant difference between ICC and adjacent noncancerous tissues (p<0.001); high expression was associated with poor histologic differentiation (p=0.019), TNM stage (p=0.014), lymph node metastasis (p=0.040), and lymphatic invasion (p=0.025). On Kaplan-Meier analysis, a comparison of survival curves of low versus high expressors of Homer1 revealed a highly significant difference in OS (p=0.001) and DFS (p=0.006), indicating that high expression of Homer1 was linked with a worse prognosis. Multivariate analyses showed that Homer1 expression was an independent risk factor predicting overall survival[Hazard ratio(HR), 7.52; 95% confidence interval (CI), 2.63-21.47; p=0.002] and disease-free survival (HR, 11.56; 95%CI, 5.17-25.96; p<0.001) in ICC. Conclusions: Homer1 promotes lymphatic invasion and associates with lymph node metastasis and poor prognosis of ICC. The current study shows that Homer1 may be an independent prognostic factor for ICC patients after curative resection, and it provides an important basis for screening/treating high-risk patients.

• Parasites, Hosts and Diseases
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• v.45 no.2 s.142
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• pp.77-85
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• 2007

Among several diagnostic tools for clonorchiasis (Clonorchis sinensis infection), radiologic examinations are commonly used in clinical practices. During the 2 past decades, many reports regarding imaging findings of clonorchiasis were introduced. The basic imaging finding of clonorchiasis is diffuse dilatation of the peripheral intra-hepatic bile ducts, without dilation of the large intrahepatic or extrahepatic bile ducts. By this finding, however, active clonorchiasis cannot be differentiated from cured infection. Some recent radiologic studies suggested specific findings of active clonorchiasis. Besides direct demonstration of worms, increased periductal echogenicity on sonography and periductal enhancement on dynamic contrast-enhanced CT or MR imaging possibly represent active clonorchiasis. Those images of the liver clonorchiasis are known to be correlated with worm burdens (EPG counts) in their frequency and also severity. The images of cholangiocarcinoma associated with clonorchiasis show both the tumor with obstruction images and diffuse dilatation of the peripheral intrahepatic bile ducts. Radiological images can be a good practical alternative diagnostic method of clonorchiasis.

• 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.13 no.5
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• pp.1995-1997
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• 2012

Background: Brain metastasis from cholangiocarcinoma (CCA) is a rare but fatal event. To the best of our knowledge, only few cases have been reported. Herein, we report the incident rate and a first case series of brain metastases from CCA. Methods: Between January 2006 and December 2010 5,164 patients were treated at Srinagarind hospital, Khon Kaen University; of those, 8 patients developed brain metastasis. Here we reviewed clinical data and survival times. Results: The incident rate of brain metastases from CCA was 0.15%. The median age of the patients was 60 years. Tumor subtypes were intrahepatic in 6 and hilar in 2 patients. All suffered from symptoms related to brain metastasis. Three patients were treated with whole-brain radiation therapy (WBRT), one of whom also underwent surgery. The median survival after the diagnosis of brain metastasis was 9.5 weeks (1-28 weeks). The longest survival observed in a patient in RPA class I with two brain lesions and received WBRT. Conclusion: This is a first case series of brain metastases from CCA with the incident rate of 0.15%. It is rare and associated with short survival time.