ORiginal Article : Silencing of CXCR4 Inhibits Tumor Cell Proliferation and Neural Invasion in Human Hilar Cholangiocarcinoma

( Xin Yu Tan ),( Shi Chang ),( Wei Liu ),( Hui Huan Tang ) The Editorial Office of Gut and Liver 2014 Gut and Liver Vol.8 No.2

Background/Aims: To evaluate the expression of CXC motif chemokine receptor 4 (CXCR4) in the tissues of patients with hilar cholangiocarcinoma (hilar-CCA) and to investigate the cell proliferation and frequency of neural invasion (NI) influenced by RNAi-mediated CXCR4 silencing. Methods: An immunohistochemical technique was used to detect the expression of CXCR4 in 41 clinical tissues, including hilar-CCA, cholangitis, and normal bile duct tissues. The effects of small interference RNA (siRNA)-mediated CXCR4 silencing were detected in the hilar-CCA cell line QBC939. Cell proliferation was determined by MTT. Expression of CXCR4 was monitored by quantitative real time polymerase chain reaction and Western blot analysis. The NI ability of hilar-CCA cells was evaluated using a perineural cell and hilar-CCA cell coculture migration assay. Results: The expression of CXCR4 was significantly induced in clinical hilar-CCA tissue. There was a positive correlation between the expression of CXCR4 and lymph node metastasis/NI in hilar-CCA patients (p<0.05). Silencing of CXCR4 in tumor cell lines by siRNA led to significantly decreased NI (p<0.05) and slightly decreased cell proliferation. Conclusions: CXCR4 is likely correlated with clinical recurrence of hilar-CCA. CXCR4 is involved in the invasion and proliferation of human hilar-CCA cell line QBC939, indicating that CXCR4 could be a promising therapeutic target for hilar-CCA. (Gut Liver 2014;8:196-204)

간문부 담관암에서 광역학 치료의 장기 성적 및 생존율 향상에 미치는 인자

안지호,천영국,조영덕,최현종,문종호,이태훈,박상흠,심찬섭 대한소화기내시경학회 2011 Clinical Endoscopy Vol.42 No.1

Background/Aims: Photodynamic therapy (PDT) has a promising effect on nonresectable cholangiocarcinoma (CC) but its long term data is not yet available. This study examined the long term outcome and factors associated with increased survival after performing PDT for hilar cholangiocarcinoma. Methods: A list of 393 patients with a diagnosis of hilar CC was retrieved from the database of Soonchunhyang University Hospital (Seoul, Korea) and these patients were seen from January 1, 2001, to April 1, 2010. We retrospectively reviewed the records of 74 patients who underwent PDT in addition to biliary stenting with/without chemoradiation. Results: The median overall survival from the date of diagnosis to death or to the last follow-up was 11.7 months (range: 2.2∼78.4). After performing PDT, a complete remission was observed in 1.3% (1/74) of the patients who had a superficial depth of tumor without lymph node involvement. On multivariate analysis using the Cox regression model, increasing the time to treatment after the diagnosis was a statistically significant predictor of shorter survival after PDT [Odds ratio: 3.25, 95% confidence interval (CI): 1.90∼4.71, p=0.034]. Conclusions: Although PDT does not prevent progression of CC, it appears to control the cholestasis. The early treatment of PDT after the diagnosis showed a survival benefit for patients with advanced hilar CC. Background/Aims: Photodynamic therapy (PDT) has a promising effect on nonresectable cholangiocarcinoma (CC) but its long term data is not yet available. This study examined the long term outcome and factors associated with increased survival after performing PDT for hilar cholangiocarcinoma. Methods: A list of 393 patients with a diagnosis of hilar CC was retrieved from the database of Soonchunhyang University Hospital (Seoul, Korea) and these patients were seen from January 1, 2001, to April 1, 2010. We retrospectively reviewed the records of 74 patients who underwent PDT in addition to biliary stenting with/without chemoradiation. Results: The median overall survival from the date of diagnosis to death or to the last follow-up was 11.7 months (range: 2.2∼78.4). After performing PDT, a complete remission was observed in 1.3% (1/74) of the patients who had a superficial depth of tumor without lymph node involvement. On multivariate analysis using the Cox regression model, increasing the time to treatment after the diagnosis was a statistically significant predictor of shorter survival after PDT [Odds ratio: 3.25, 95% confidence interval (CI): 1.90∼4.71, p=0.034]. Conclusions: Although PDT does not prevent progression of CC, it appears to control the cholestasis. The early treatment of PDT after the diagnosis showed a survival benefit for patients with advanced hilar CC

Comparison of the clinical results of surgical resection for extrahepatic cholangiocarcinomas: Hilar cholangiocarcinoma and mid-to-distal cholangiocarcinoma

Pyung Jung,Eung-Ho Cho,Sang-Bum Kim,Ryoung-Go Kim 한국간담췌외과학회 2019 Annals of hepato-biliary-pancreatic surgery Vol.23 No.4

Backgrounds/Aims: Hilar cholangiocarcinomas (HLC) are known to have worse prognoses than mid-to-distal cholangiocarcinomas (CBDC). We analyzed the clinical results of surgical resections for extrahepatic cholangiocarcinomas to validate the differences in the prognoses of HLC and CBDC. Methods: Two hundred and eighty-one patients underwent curative surgical resections for extrahepatic cholangiocarcinomas at the Department of Surgery in the Korea Cancer Center Hospital. Among them, we analyzed the T2 and T3 patients and compared the clinical results between those with HLC (n=74) and those with CBDC (n=65). Results: The rate of R1 resections was significantly higher in the HLC patients compared to the CBDC patients (31.1% vs 12.3%, p=0.006). The overall survival rate of the T2/T3 patients was lower in the HLC group than in the CBDC group (24.5% vs 51.7, p=0.039). The recurrence-free survival rate was 23.3% in the HCL patients and 50.9% in the CBDC patients (p=0.06). In the subgroup analysis, the survival rates were not different in patients who had lymph node metastases or in patients who underwent R1 resections between the HLC and CBDC patients. Poor independent prognostic factors for the overall and recurrence-free survival rates in the T2/T3 extrahepatic cholangiocarcinoma patients were the presence of lymph node metastases and the hilar locations of tumor. Conclusions: HLC patients had poorer prognoses than CBDC patients. However, in patients with lymph node metastases, the prognosis was poor and was not different between the HLC and CBDC patients. Other adjuvant treatment methods are needed for extrahepatic cholangiocarcinoma patients with lymph node metastases to improve their prognoses.

Review : Endoscopic drainage in patients with inoperable hilar cholangiocarcinoma

( Ye Jin Park ),( Dae Hwan Kang ) 대한내과학회 2013 The Korean Journal of Internal Medicine Vol.28 No.1

Hilar cholangiocarcinoma has an extremely poor prognosis and is usually diagnosed at an advanced stage. Palliative management plays an important role in the treatment of patients with inoperable hilar cholangiocarcinoma. Surgical, percutaneous, and endoscopic biliary drainage are three modalities available to resolve obstructive jaundice. Plastic stents were widely used in the past; however, self-expanding metal stents (SEMS) have become popular recently due to their long patency and reduced risk of side branch obstruction, and SEMS are now the accepted treatment of choice for hilar cholangiocarcinoma. Bilateral drainage provides more normal and physiological biliary flow through the biliary ductal system than that of unilateral drainage. Unilateral drainage was preferred until recently because of its technical simplicity. But, with advancements in technology, bilateral drainage now achieves a high success rate and is the preferred treatment modality in many centers. However, the choice of unilateral or bilateral drainage is still controversial, and more studies are needed. This review focuses on the endoscopic method and discusses stent materials and types of procedures for patients with a hilar cholangiocarcinoma.

간문부 담관암의 경피적 담도 스텐트를 이용한 치료

김창원 부산대학교 병원 암연구소 2006 부산대병원학술지 Vol.- No.20

Purpose: Percutaneous internal drainage is a well-established palliative treatment for unresectable hilar cholangiocarcinoma. This study evaluated the clinical efficacy of bilateral drainage with percutaneous dual stent placement for the treatment of hilar cholangiocarcinoma. Subject and Methods: From 2001 to 2005, 53 patients with hilar cholangiocarcinoma were treated with the percutaneous placement of two self-expandable metallic endoprostheses in a T configuration or a Y configuration. The outcomes were examined retrospectively. Results: Forty six hilar cholangiocarcinomas were drained by aT-configured stent and 7 cases were drained by a Y-configured stent. Procedure related cholangitis occurred in 4 out of 53 patients (7%). The mean survival and stent patency times were 316 and 241 days, respectively. There were no statistically significant differences in the frequency of cholangitis, survival and stent patency between the groups of T and Y configured stents. Conclusions: Percutaneous internal drainage with T-configured or Y-configured dual stent placement can be used effectively in hilar cholangiocarcinomas.

Intraductal ultrasonography combined with percutaneous transhepatic cholangioscopy for the preoperative evaluation of longitudinal tumor extent in hilar cholangiocarcinoma

Kim, Hee Man,Park, Jeong Youp,Kim, Kyung Sik,Park, Mi-Suk,Kim, Myeong-Jin,Park, Young Nyun,Bang, Seungmin,Song, Si Young,Chung, Jae Bock,Park, Seung Woo Blackwell Publishing Asia 2010 Journal of gastroenterology and hepatology Vol.25 No.2

<P>Abstract</P><P>Background and Aim: </P><P>In hilar cholangiocarcinoma, an accurate assessment of preoperative resectability is important to optimize surgical resection. We investigated the accuracy of the combination of intraductal ultrasonography (IDUS) and percutaneous transhepatic cholangioscopy (PTCS) for evaluating longitudinal extent in hilar cholangiocarcinoma.</P><P>Methods: </P><P>Patients diagnosed with hilar cholangiocarcinoma underwent multidetector computed tomography (MDCT) and magnetic resonance cholangiography (MRC) for tumor staging and Bismuth type. Percutaneous transhepatic biliary drainage was performed at the left or right bile duct of the liver section that was anticipated to be preserved in the surgical treatment. After tract dilation, PTCS with cholangioscope-directed biopsy and IDUS were sequentially performed to evaluate Bismuth type. Surgical treatment was executed according to tumor staging and longitudinal tumor extent. Postoperative histological Bismuth types were compared to preoperative Bismuth types based on MDCT, MRC, PTCS with biopsy, and IDUS.</P><P>Results: </P><P>From June 2006 to November 2008, 25 patients with hilar cholangiocarcinoma were enrolled, with 20 of these patients evaluable. The accuracy of MDCT, MRC, PTCS with biopsy, and IDUS for the evaluation of Bismuth type was 80%, 84.2%, 90%, and 85.0%, respectively, in 20 patients, and 82.4%, 82.4%, 94.1%, and 88.2%, respectively, in 18 patients with Bismuth type IIIa, IIIb, or IV cancer. The accuracy of the combination of IDUS and PTCS with biopsy was 95% in 20 patients, and 100% in 18 with Bismuth type IIIa, IIIb, or IV cancer.</P><P>Conclusions: </P><P>The combination of IDUS and PTCS with biopsy was highly accurate for assessing Bismuth type and may help in the identification of an optimal surgical plan for the treatment of hilar cholangiocarcinoma, especially in Bismuth type IIIa, IIIb, or IV. </P>

HCC : PE-072 ; Hilar inflammatory pseudotumor mimicking hilar cholangiocarcinoma

( Min Jung Kim ),( Hee Seok Moon ),( Eaum Seok Lee ),( Seok Hyun Kim ),( Byung Seok Lee ),( Heon Young Lee ) 대한간학회 2012 춘·추계 학술대회 (KASL) Vol.2012 No.-

Background: Inflammatory pseudotumor (IPT) of the biliary tract is a benign disease, and is a rare clinical and pathological entity. These tumors were so named because of the difficulty in distinguishing them from malignant lesions preoperatively. Thus, the clinical manifestations and imaging appearance of the tumor are similar to those of a malignant neoplasm of the biliary tract, its diagnosis often depends on pathological examination after operation. We present a case of IPT located at the porta hepatis, and elucidate that IPT in the right hepatic duct is especially difficult to distinguish from hilar cholangiocarcinoma. Case: A 81-year-old woman was admitted to our hospital with right upper quadrant abdominal pain. Blood tests showed increased serum ALP (239IU/L) and GGT (393IU/L), but hepatic parenchymal enzymes were normal. The level of serum AFP, CEA and CA19-9 were within normal ranges. The MRI showed abrupt obstruction of confluent portion of right IHD at liver hilum with dilatation of perihilar IHD, suggesting hilar cholangiocarcinoma initially. The patient underwent Rt. hepatectomy with Roux-en-Y hepaticojejunostomy. Histologically, the tumor confirmed a diagnosis of IPT of the plasma cell type. Conclusions: IPT is a non-specific chronic inflammatory lesion, however its pathogenesis and etiology remains unknown. Patients with IPT of the hepatic hilar biliary duct present with fever, jaundice, and manifestations indistinguishable from those of cholangiocarcinoma. Thus, patients with symptoms such as abdominal pain and jaundice, cases in whom the tumor mass tends to increase, and those in whom making the diagnosis is difficult, should be recommended to undergo surgical resection.

HCC : PE-072 ; Hilar inflammatory pseudotumor mimicking hilar cholangiocarcinoma

( Min Jung Kim ),( Hee Seok Moon ),( Eaum Seok Lee ),( Seok Hyun Kim ),( Byung Seok Lee ),( Heon Young Lee ) 대한간학회 2012 춘·추계 학술대회 (KASL) Vol.2012 No.1

Background: Inflammatory pseudotumor (IPT) of the biliary tract is a benign disease, and is a rare clinical and pathological entity. These tumors were so named because of the difficulty in distinguishing them from malignant lesions preoperatively. Thus, the clinical manifestations and imaging appearance of the tumor are similar to those of a malignant neoplasm of the biliary tract, its diagnosis often depends on pathological examination after operation. We present a case of IPT located at the porta hepatis, and elucidate that IPT in the right hepatic duct is especially difficult to distinguish from hilar cholangiocarcinoma. Case: A 81-year-old woman was admitted to our hospital with right upper quadrant abdominal pain. Blood tests showed increased serum ALP (239IU/L) and GGT (393IU/L), but hepatic parenchymal enzymes were normal. The level of serum AFP, CEA and CA19-9 were within normal ranges. The MRI showed abrupt obstruction of confluent portion of right IHD at liver hilum with dilatation of perihilar IHD, suggesting hilar cholangiocarcinoma initially. The patient underwent Rt. hepatectomy with Roux-en-Y hepaticojejunostomy. Histologically, the tumor confirmed a diagnosis of IPT of the plasma cell type. Conclusions: IPT is a non-specific chronic inflammatory lesion, however its pathogenesis and etiology remains unknown. Patients with IPT of the hepatic hilar biliary duct present with fever, jaundice, and manifestations indistinguishable from those of cholangiocarcinoma. Thus, patients with symptoms such as abdominal pain and jaundice, cases in whom the tumor mass tends to increase, and those in whom making the diagnosis is difficult, should be recommended to undergo surgical resection.

간문부 담관암의 임상적 고찰

한민수(M . S . Han),홍성화(S . H . Hong),이상목(S . M . Lee),장린(R . Chang),이정일(J . I . Lee),장영운(Y . W . Chang),김병호(B . H . Kim),김효종(H . J . Kim),동석호(S . H . Dong) 대한내과학회 1996 대한내과학회지 Vol.50 No.2

N/A Objectives: There is no difficulty in the diagnosis of hilar cholangiocarcinoma because of early occurrence of obstructive jaundice. Though prolonged survival can be expected with surgical resection, being advanced stage at the time of diagnosis, radical resection has been impossible in most cases. Recently the significant interest has been focused on this lesion and the aggressive surgical resection increased, but the results were various. Thus, the present study was performed to evaulate the clinical characteristics of hilar cholangiocarcinoma. Methods: We evaluated retrospectively 63 cases of hilar cholangiocarcinoma which were diagnosed at Kyung Hee University Hospital from January 1988 to July 1994. Results: 1) The mean age of the patients was 58±12.0 years and the ratio of male to female was 2.9: 1. 2) Jaundice was the most common symptom (85.7%) followed by abdominel pain(53.9%), weight loss (34.9%) and pruritus(30.1%). 3) Of 13 cases(20.6%) who underwent surgical resection, 7 cases(11.1%) had curative resection. PTBD was performed in 4i cases(73%), radiotherapy in 7 cases(11.1%), chemotherapy in 4 cases (6.3%) and metallic stent insertion in 7 cases (11.1%). 4) The mean survival time was 15.3±3.0 months in resection group(13 cases, 20.6%) and 4.8±0.5 months in non-resection group(50 cases, 79.4%). The survival time of resection group was longer than that of non-resection group(p<0.01). Conclusion: In conclusion, the prognosis of hilar cholangiocarcinoma is extremely poor and the prolonged survival can be expected with surgical resection. Thus, to determine the resectability, early diagnosis is important and accurate preoperative staging is necessary

Chronological analysis of surgical and oncological outcomes after the treatment of perihilar cholangiocarcinoma

Sung Ho Lee,Gi Hong Choi,Dai Hoon Han,Kyung Sik Kim,Jin Sub Choi,Seoung Yoon Rho 한국간담췌외과학회 2021 Annals of hepato-biliary-pancreatic surgery Vol.25 No.1

Backgrounds/Aims: Despite advances in surgical techniques and perioperative supportive care, radical resection of hilar cholangiocarcinoma is the only modality that can achieve long-term survival. We chronologically investigated surgical and oncological outcomes of hilar cholangiocarcinoma and analyzed the factors affecting overall survival. Methods: We retrospectively enrolled 165 patients with hilar cholangiocarcinoma who underwent liver resection with a curative intent. The patients were divided into groups based on the period when the surgery was performed: period I (2005-2011) and period II (2012-2018). The clinicopathological characteristics, perioperative outcomes, and survival outcomes were analyzed. Results: The patients’ age, serum CA19-9 levels, and serum bilirubin levels at diagnosis were significantly higher in the period I group. There were no differences in pathological characteristics such as tumor stage, histopathologic status, and resection status. However, perioperative outcomes, such as estimated blood loss (1528.8 vs. 1034.1 mL, p=0.020) and postoperative severe complication rate (51.3% vs. 26.4%, p=0.022), were significantly lower in the period II group. Regression analysis demonstrated that period I (hazard ratio [HR]=1.591; 95% confidence interval [CI]=1.049-2.414; p=0.029), preoperative serum bilirubin at diagnosis (HR=1.585; 95% CI=1.058-2.374; p=0.026), and tumor stage (III, IV) (HR=1.671; 95% CI: 1.133-2.464; p=0.010) were significantly associated with poor prognosis. The 5-year survival rate was better in the period II patients than in the period I patients (35.1% vs. 21.0%, p=0.0071). Conclusions: The surgical and oncological outcomes were better in period II. Preoperative serum bilirubin and advanced tumor stage were associated with poor prognosis in patients with hilar cholangiocarcinoma.