• Radiation Oncology Journal
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• 제10권1호
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• pp.49-58
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• 1992

1986년 1월부터 1990년 9월까지 7예의 간외담도계 암 환자를 대상으로 외부 방사선치료와 온열치료를 병행하였다. 7예중 3예는 간외담도암으로 이중 2예는 원발성 담도암 이었고 1예는 위암에서 담도주위로 전이된 암이었다. 7예중 나머지 4예는 담낭암으로 이중 2예는 담낭 절제후 국소적으로 재발된 암이었고 나머지 2예는 원발성 담낭암 이었다. 그리고 7예는 모두 선암으로 확인 되었다. 조사된 방사선의 양은 3000 cGy/2주 조사한 1예를 제외하고 6예에서는 $4500\~5040\;cGY/6\~7$주 조사되었다. 온열치료는 모든 환자에서 방사선치료후 30분 이내에 시행되었으며 방사선치료 기간동안 주 1회 내지 2회씩 총 4회에서 12회까지 시행되었다. 치료효과의 판정은 T-관 T-관 담도촬영술. PTC, 그리고 CT등의 소견으로 하였으며 7예중 6예($86\%$)에서 부분관해를 보였으며 완전관해는 없었다. 7예중 6예는 4개월에서 11개월 애내 사망하였으며 나머지 1예는 현재 11개월째 생존하고 있으나 치료부위 밖에서 국소전이가 관찰되었다. 그리고 7예환자의 정중생존기간은 7개월이었다. 사망환자 6예의 사망원인으로는 원발성 담도암환자 1예에서 폐혈증, 전이성 담도암환자에서 원격 전이, 나머지 4예에서는 원발병소의 진행이 확인되었다. 관찰기간이 짧았으나 모든 환자에서 치료에 잘 적응하였으며 간, 십이지장, 위내의 합병증은 없었고 전이성 담도암 환자에서 일과성 카보닐산혈증이 관찰되었다.

• Asian Pacific Journal of Cancer Prevention
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• 제13권11호
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• pp.5381-5384
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• 2012

Background and Aim: Cholangiocarcinoma (CCA) is an uncommon malignancy of the bile duct, occurring in nearly 2 out of 100,000 people. It is a type of adenocarcinoma that originates in the mucous glands of the epithelium, or surface layers of the bile ducts. The aim of this study was to evaluate the clinical features, diagnostic results and factors associated with survival, morbidity and mortalityof cholangiocarcinoma cases in Iranian patients. Method: In this retrospective study the hospital medical records of 283 patients with a primary or final diagnosis of cholangiocarcinoma who had been admitted to gastroenterology ward of our hospital from 2004 to 2011 were retrospectively reviewed. Results: 283 patients (180 male, 63%, and 103 female, 38.6%) with a mean age of $59.7{\pm}14.4$ years were studied. The most frequent symptoms were painless jaundice (190, 66.9%), abdominal pain (77, 27%), pruritus 133 (46.8%) and weight loss (169, 59.5%). The most frequent associated risk factors and diseases were as follows: gallstones (72, 25.4%), diabetes (70, 24.6%), HBV infection (52 (18.3%), HCV infection 43 (15%), primary sclerosing cholangitis (16, 5.6%) and smoking (120, 42.3%). The most frequent type of cholangiocarcinoma in ERCP and MRCP was hilar. The mean survival time was $7.42{\pm}5.76$ months. Conclusion: The mean survival time in our study was lower than one year. Moreover the most frequent risk factors and associated diseases were smoking, gallstones and diabetes. Painless jaundice, abdominal pain and weight loss were the most clinical features related to cholangiocarcinoma. Additionally survival time did not correlate with risk factors, associated diseases and clinical presentations, but was linked to biliary metallic stenting and surgery.

• Asian Pacific Journal of Cancer Prevention
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• 제16권5호
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• pp.1737-1742
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• 2015

Background: Mitochondrial DNA (mtDNA) mutations have been shown to be associated with cancer. This study explored whether mtDNA mutations enhance cholangiocarcinoma (CCA) development in individuals. Materials and Methods: The whole mitochondrial genome sequences of 25 CCA patient tissues were determined and compared to those of white blood cells from the corresponding individuals and 12 healthy controls. The mitochondrial genome was amplified using primers from Mitoseq and compared with the Cambridge Reference Sequence. Results: A total of 161 mutations were identified in CCA tissues and the corresponding white blood cells, indicating germline origins. Sixty-five (40%) were new. Nine mutations, representing those most frequently observed in CCA were tested on the larger cohort of 60 CCA patients and 55 controls. Similar occurrence frequencies were observed in both groups. Conclusions: While the correspondence between the cancer and mitochondrial genome mutation was low, it is of interest to explore the functions of the missense mutations in a larger cohort, given the possibility of targeting mitochondria for cancer markers and therapy in the future.

• Asian Pacific Journal of Cancer Prevention
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• 제13권5호
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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.

• Journal of Digestive Cancer Research
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• 제5권1호
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• pp.50-54
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• 2017

Pancreatic neuroendocrine tumors are rare pancreatic neoplasms comprising 1-2% of all pancreatic tumors and typically present high attenuating mass on arterial and venous phase images, due to their rich capillary network. A 70-year-old South Korean female visited our hospital presenting with jaundice and dark urine color. She had received an operation for treatment of small bowel perforation seven years ago. On physical examination, icteric sclera was observed but otherwise unremarkable. Laboratory tests were abnormal liver function test and suspected obstructive jaundice. Computed tomography revealed 4 cm sized cystic mass lesion with homogeneous low attenuation in the head of pancreas and distal common bile duct was compressed by the mass. During review of past medical records, we found that the mass was observed and measured about 1.7 cm seven years ago. To resolve obstructive jaundice, pylorus preserving pancreaticoduodenectomy was performed and diagnosed with well differentiated pancreatic neuroendocrine carcinoma with intermediate grade.

• Journal of Digestive Cancer Reports
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• 제7권1호
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• pp.18-21
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• 2019

Serine protease inhibitor Kazal-type 1 (SPINK1) is a gene expressed from pancreatic acinar cell which its mutation is known to be associated with chronic pancreatitis (CP) and pancreatic cancer. We report a case of a 47-years-old female with nausea and weight loss with yellow discoloration of skin. Initial imaging and endoscopic study led us to an impression of chronic pancreatitis with pancreatic cancer with common bile-duct dilation. Biopsy result was confirmed with pancreatic adenocarcinoma and additional imaging revealed lymph node and bone metastasis. Our genetic analysis revealed 194+2T>C mutation of SPINK1. Biliary obstruction was successfully decompressed by stent insertion and underwent chemotherapy and radiotherapy. Although there is accumulating evidence of association between SPINK1 mutation and CP, the relationship between SPINK1 mutation and pancreatic cancer in CP patient is an emerging concept. Genetic analysis should be considered in patients with young age especially when diagnosed with both CP and pancreatic cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제17권1호
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• pp.201-205
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• 2016

Cholangiocarcinoma (CCA) is generally a rare primary liver tumor of the bile duct with extremely poor clinical outcomes due to late diagnosis. Osteopontin (OPN) is the most abundant expressed gene in intrahepatic CCA and its involvement in tumor aggressiveness suggests it could be a useful prognostic biomarker. However, the prognostic significance of OPN expression in CCA is still controversial. We therefore immunohistochemically studied OPN expression in 354 resected CCAs and correlated the results with patient clinicopathological parameters. OPN expression was separately scored according to the percentage of cancer cells or degree of stromal tissue staining and classified as low (score 0-1) and high (score 2-3). OPN expression in CCA cells was found in 177 out of 354 patients (56.5%), whereas stroma was positive in 185 out of 354 patients (52.3%). Univariate analysis with several of the aforementioned parameters revealed that stromal but not cancer cell OPN expression was significantly associated with tumor size, tumor direct invasion into normal liver parenchyma, regional lymph node metastasis and higher staging. The combination of cancer cell and stromal OPN expression demonstrated a positive trend for linkage with lymph node metastasis. Multivariate analysis identified gender, the presence of lymphatic permeation and lymph node metastasis, but not OPN expression, as independent prognostic factors. This study confirms the presence of stromal OPN expression in tumor aggressiveness but not survival in CCA patients.

• BMB Reports
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• 제56권11호
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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.

• Asian Pacific Journal of Cancer Prevention
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• 제16권18호
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• pp.8079-8083
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• 2016

Metformin is an oral anti-hyperglycemic agent, which is the most commonly prescribed medication in the treatment of type-2 diabetes mellitus. It is purportedly associated with a reduced risk for various cancers, mainly exerting anti-proliferation effects on various human cancer cell types, such as pancreas, prostate, breast, stomach and liver. This mini-review highlights the risk and benefit of metformin used for cholangiocarcinoma (CCA) prevention and therapy. The results indicated metformin might be a quite promising strategy CCA prevention and treatment, one mechanism being inhibition of CCA tumor growth by cell cycle arrest in both in vitro and in vivo. The AMPK/mTORC1 pathway in intrahepatic CCA cells is targeted by metformin. Furthermore, metformin inhibited CCA tumor growth via the regulation of Drosha-mediated expression of multiple carcinogenic miRNAs. The use of metformin seems to be safe in patients with cirrhosis, and provides a survival benefit. Once hepatic malignancies are already established, metformin does not offer any therapeutic potential. Clinical trials and epidemiological studies of the benefit of metformin use for CCA should be conducted. To date, whether metformin as a prospective chemotherapeutic for CCA is still questionable and waits further atttention.

• Asian Pacific Journal of Cancer Prevention
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• 제16권9호
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• pp.3849-3856
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• 2015

Background: Cholangiocarcinoma (CCA), or bile duct cancer, is incurable with a high mortality rate due to a lack of effective early diagnosis and treatment. Identifying cytoplasmic membrane proteins of invasive CCA that facilitate cancer progression would contribute toward the development of novel tumor markers and effective chemotherapy. Materials and Methods: An invasive CCA cell line (KKU-100) was stimulated using TNF-${\alpha}$ and then biotinylated and purified for mass spectrometry analysis. Novel proteins expressed were selected and their mRNAs expression levels were determined by real-time RT-PCR. In addition, the expression of ALCAM was selected for further observation by Western blot analysis, immunofluorescent imaging, and antibody neutralization assay. Results: After comparing the proteomics profile of TNF-${\alpha}$ induced invasive with non-treated control cells, over-expression of seven novel proteins was observed in the cytoplasmic membrane of TNF-${\alpha}$ stimulated CCA cells. Among these, ALCAM is a novel candidate which showed significant higher mRNA- and protein levels. Immunofluorescent assay also supported that ALCAM was expressed on the cell membrane of the cancer, with increasing intensity associated with TNF-${\alpha}$. Conclusions: This study indicated that ALCAM may be a novel protein candidate expressed on cytoplasmic membranes of invasive CCA cells that could be used as a biomarker for development of diagnosis, prognosis, and drug or antibody-based targeted therapies in the future.