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Zhang D, Shen T, Gao F, Sun Y, Dai Z, Luo H, Sun Y, Yang Z, Gu J. Endoscopic treatment of unresectable perihilar cholangiocarcinoma: beyond biliary drainage. Therap Adv Gastroenterol 2025; 18:17562848251328595. [PMID: 40292090 PMCID: PMC12033555 DOI: 10.1177/17562848251328595] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2024] [Accepted: 02/27/2025] [Indexed: 04/30/2025] Open
Abstract
Perihilar cholangiocarcinoma (PHCC) is an aggressive biliary malignancy originating from the epithelial cells of the bile duct, typically located in the extrahepatic biliary tree, proximal to the cystic duct. PHCC often presents with a rapid onset of jaundice. While radical surgical resection remains the only curative treatment, only a minority of patients are eligible due to early metastasis and challenges associated with preoperative evaluations. Comprehensive treatments, including chemotherapy, radiotherapy, targeted therapy, and immunotherapy, are crucial for managing PHCC. However, in advanced stages, complications such as cholestatic liver injury, malnutrition, and biliary infections pose significant obstacles to these treatments. Therefore, biliary drainage (BD) is essential in the management of PHCC. In addition to external drainage methods like percutaneous transhepatic biliary drainage (PTBD), endoscopic biliary drainage (EBD), particularly endoscopic retrograde cholangiopancreatography (ERCP), offer an effective option for internal drainage, which is more physiologically compatible and better tolerated. Furthermore, the integration of various endoscopic techniques has expanded the management of PHCC beyond mere drainage. Techniques such as radiofrequency ablation (RFA), photodynamic therapy (PDT), and endoscopic ultrasound (EUS) based methods present new therapeutic avenues, albeit with variable results. This review aims to summarize current advancements and ongoing debates in the field of endoscopic treatment for unresectable PHCC.
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Affiliation(s)
- Di Zhang
- Department of Endoscope, General Hospital of Northern Theater Command, Shenyang, Liaoning, China
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China
| | - Tianci Shen
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China
| | - Feng Gao
- Department of Endoscope, General Hospital of Northern Theater Command, Shenyang, Liaoning, China
| | - Yong Sun
- Department of Endoscope, General Hospital of Northern Theater Command, Shenyang, Liaoning, China
| | - Zihao Dai
- Department of Endoscope, General Hospital of Northern Theater Command, Shenyang, Liaoning, China
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China
| | - Haifeng Luo
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China
| | - Yanan Sun
- Department of Endoscope, General Hospital of Northern Theater Command, Shenyang, Liaoning, China
| | - Zhuo Yang
- Department of Endoscope, General Hospital of Northern Theater Command, No. 83, Wenhua Road, Shenhe District, Shenyang, Liaoning 110016, China
| | - Jiangning Gu
- Department of Endoscope, General Hospital of Northern Theater Command, No. 83, Wenhua Road, Shenhe District, Shenyang, Liaoning 110016, China
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Chen H, Li H, Li H, Zhang Z. Umbrella review of adjuvant photodynamic therapy for cholangiocarcinoma palliative treatment. Photodiagnosis Photodyn Ther 2025; 51:104472. [PMID: 39761808 DOI: 10.1016/j.pdpdt.2025.104472] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2024] [Revised: 12/31/2024] [Accepted: 01/03/2025] [Indexed: 01/24/2025]
Abstract
BACKGROUND Cholangiocarcinoma is a rare and often fatal malignancy. Numerous studies have demonstrated promising outcomes and survival rates associated with adjuvant photodynamic therapy (PDT) in the palliative treatment of cholangiocarcinoma. OBJECTIVE To systematically evaluate the existing meta-analyses on PDT for cholangiocarcinoma, assessing evidence quality and strength while performing updated meta-analyses to refine survival outcomes. METHODS PubMed, EMBASE, Cochrane Library, and Web of Science were systematically searched up to September 18, 2024, to identify meta-analyses and clinical studies on PDT in patients with cholangiocarcinoma. The random-effects model was employed to re-synthesize existing meta-analyses, with a comprehensive evaluation of methodological quality. Updated meta-analyses of survival data were conducted, including subgroup analyses stratified by cholangiocarcinoma type and intervention modality. RESULTS A total of 5 meta-analyses and 21 clinical studies were included. The findings indicated that combining PDT with stenting or chemotherapy can significantly improve overall survival in patients with cholangiocarcinoma and reduce mortality rate, without increasing the risk of adverse events (AEs) such as cholangitis or abscess formation. For extrahepatic cholangiocarcinoma, adding PDT to stenting demonstrated a notable improvement in the 2-year survival rate. Meanwhile, for hilar cholangiocarcinoma, the addition of chemotherapy to PDT showed a more pronounced enhancement in the 1-year survival rate. CONCLUSION Current evidence indicates that PDT combined with stenting or chemotherapy in the palliative treatment of cholangiocarcinoma decreases overall mortality and enhances OS without increasing the incidence of AEs. Adding PDT to stenting or chemotherapy may be more beneficial for long-term efficacy.
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Affiliation(s)
- Hanhan Chen
- Department of Breast and Thyroid Surgery, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
| | - Honglin Li
- Traditional Chinese Medicine, Shandong Provincial Hospital affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Huijie Li
- Department of Oncology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
| | - Zhen Zhang
- Department of Radiation Oncology, The Third Affiliated Hospital of Shandong First Medical University (Affiliated Hospital of Shandong Academy of Medical Sciences), Jinan, Shandong, China.
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Dong S, Jiang A, Liu Q, An S. Photodynamic Therapy or Palliative Resection Versus Biliary Stenting for Advanced Cholangiocarcinoma: A Network Meta-Analysis. Photobiomodul Photomed Laser Surg 2024; 42:737-746. [PMID: 39588663 DOI: 10.1089/photob.2024.0080] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2024] Open
Abstract
Background: We assessed the efficacy of evaluating palliative resection (R1/R2 resection), photodynamic therapy (PDT), and biliary stenting (stent) alone in the treatment of advanced cholangiocarcinoma using a reticulated meta-analysis. Methods: A systematical retrieval in PubMed, Web of Science, and the Cochrane Library was performed for relative literature on the effects of PDT, palliative resection, and simple biliary stenting in the treatment of advanced cholangiocarcinoma. A literature search updated to January 30, 2024, was performed. Newcastle-Ottawa Scale and Risk Of Bias In Non-randomised Studies-of Interventions (ROBINS-I) tools were used to assess the methodological quality of the included studies, and Addis-1.16 0.6 software for reticulated meta-analysis. Results: The results showed that PDT and palliative resection were superior to biliary stenting alone in improving 1-, 2-, and 3-year survivals, and the incidence of cholangitis. The relative effectiveness of PDT, palliative resection, and biliary stent placement alone in improving survival was as follows: PDT, palliative resection, and biliary stent placement alone. Conclusion: There is no significant difference between PDT and palliative resection in improving patient survival time, and PDT does not increase the incidence of cholangitis.
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Affiliation(s)
| | - An Jiang
- Department of hepatobiliary pancreas and liver transplantation, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Qifan Liu
- Xi'an Jiaotong University, Xi'an, China
| | - Shiqi An
- Xi'an Jiaotong University, Xi'an, China
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Kim M, Parekh D, Kahaleh M. Ablation Therapy of the Biliary Tree: Status and Comprehensive Review. J Clin Gastroenterol 2024; 58:317-323. [PMID: 38252680 DOI: 10.1097/mcg.0000000000001965] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2023] [Accepted: 12/13/2023] [Indexed: 01/24/2024]
Abstract
Malignant biliary obstruction is typically referred to endoscopists for palliation. A curative resection is indeed rarely an option in this condition. Photodynamic therapy and radiofrequency ablation are 2 modalities that can be offered in those patients. Many studies have demonstrated improved stent patency and survival after ablation. Photodynamic therapy is unfortunately very expensive and is associated with photosensitivity; however, it transmits to the entire biliary tree. Radiofrequency ablation is more affordable and easier to apply but requires contact with the tumor to be efficient. This review explores both modalities in terms of their safety and efficacy for bile duct cancer palliation.
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Affiliation(s)
- Marina Kim
- University of Massachusetts, Worcester, MA
| | - Darshan Parekh
- Thane Institute of Gastroenterology, Thane, Maharashtra, India
| | - Michel Kahaleh
- Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ
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Li Y, Li Y, Song Y, Liu S. Advances in research and application of photodynamic therapy in cholangiocarcinoma (Review). Oncol Rep 2024; 51:53. [PMID: 38334150 DOI: 10.3892/or.2024.8712] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2023] [Accepted: 01/18/2024] [Indexed: 02/10/2024] Open
Abstract
Cholangiocarcinoma (CCA) is a disease characterized by insidious clinical manifestations and challenging to diagnose. Patients are usually diagnosed at an advanced stage and miss the opportunity for radical surgery. Therefore, effective palliative therapy is the main treatment approach for unresectable CCA. Current common palliative treatments include biliary drainage, chemotherapy, radiotherapy, targeted therapy and immunotherapy. However, these treatments only offer limited improvement in quality of life and survival. Photodynamic therapy (PDT) is a novel local treatment method that is considered a safe tumor ablation method for numerous cancers. It has shown good efficacy in various studies of CCA and is expected to become an important treatment for CCA. In the present study, the mechanisms of PDT in the treatment of CCA were systematically explored and the progress in the research of photosensitizers was discussed. The current study focused on the various PDT protocols and their therapeutic effects in CCA, with the objective of providing a new horizon for future research and clinical applications of PDT in the treatment of CCA.
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Affiliation(s)
- Yufeng Li
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan 410005, P.R. China
| | - Yuhang Li
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan 410005, P.R. China
| | - Yinghui Song
- Central Laboratory of Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, Hunan 410005, P.R. China
| | - Sulai Liu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan 410005, P.R. China
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Nabi Z, Żorniak M, Reddy DN. Multimodal treatment with endoscopic ablation and systemic therapy for cholangiocarcinoma. Best Pract Res Clin Gastroenterol 2024; 68:101893. [PMID: 38522890 DOI: 10.1016/j.bpg.2024.101893] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2023] [Revised: 02/03/2024] [Accepted: 02/15/2024] [Indexed: 03/26/2024]
Abstract
Cholangiocarcinoma (CCA) are primary malignancies of biliary system and usually unresectable at the time of diagnosis. As a consequence, majority of these cases are candidates for palliative care. With the advances in chemotherapeutic agents and multidisciplinary care, the survival rate has improved in cases with inoperable malignant biliary obstruction. As a consequence, there is a need to provide effective and durable palliative care in these patients. The main role of endoscopic palliation in the vast majority of CCA includes biliary stenting for obstructive jaundice. Recent advances in the endoscopic palliation and multimodal approach appear promising in imparting durable relief of symptoms. Use of radiofrequency ablation, photodynamic therapy and intraluminal brachytherapy has been shown to improve the survival rates as well as the patency of biliary stents. Infact, intraductal ablation may act synergistically with chemotherapy by modulating tumour signalling pathways and immune microenvironment.
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Affiliation(s)
- Zaheer Nabi
- Asian Institute of Gastroenterology, Hyderabad, India.
| | - Michał Żorniak
- Endoscopy Unit, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Poland.
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Kuwatani M, Sakamoto N. Promising Highly Targeted Therapies for Cholangiocarcinoma: A Review and Future Perspectives. Cancers (Basel) 2023; 15:3686. [PMID: 37509347 PMCID: PMC10378186 DOI: 10.3390/cancers15143686] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Revised: 07/16/2023] [Accepted: 07/17/2023] [Indexed: 07/30/2023] Open
Abstract
To overcome the poor prognosis of cholangiocarcinoma (CCA), highly targeted therapies, such as antibody-drug conjugates (ADCs), photodynamic therapy (PDT) with/without systemic chemotherapy, and experimental photoimmunotherapy (PIT), have been developed. Three preclinical trials have investigated the use of ADCs targeting specific antigens, namely HER2, MUC1, and glypican-1 (GPC1), for CCA. Trastuzumab emtansine demonstrated higher antiproliferative activity in CCA cells expressing higher levels of HER2. Similarly, "staphylococcal enterotoxin A-MUC1 antibody" and "anti-GPC1 antibody-monomethyl auristatin F" conjugates showed anticancer activity. PDT is effective in areas where appropriate photosensitizers and light coexist. Its mechanism involves photosensitizer excitation and subsequent reactive oxygen species production in cancer cells upon irradiation. Hematoporphyrin derivatives, temoporfin, phthalocyanine-4, talaporfin, and chlorine e6 derivatives have mainly been used clinically and preclinically in bile duct cancer. Currently, new forms of photosensitizers with nanotechnology and novel irradiation catheters are being developed. PIT is the most novel anti-cancer therapy developed in 2011 that selectively kills targeted cancer cells using a unique photosensitizer called "IR700" conjugated with an antibody specific for cancer cells. PIT is currently in the early stages of development for identifying appropriate CCA cell targets and irradiation devices. Future human and artificial intelligence collaboration has potential for overcoming challenges related to identifying universal CCA cell targets. This could pave the way for highly targeted therapies for CCA, such as ADC, PDT, and PIT.
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Affiliation(s)
- Masaki Kuwatani
- Department of Gastroenterology and Hepatology, Hokkaido University Hospital, North 14, West 5, Kita-ku, Sapporo 060-8648, Japan
| | - Naoya Sakamoto
- Department of Gastroenterology and Hepatology, Hokkaido University Hospital, North 14, West 5, Kita-ku, Sapporo 060-8648, Japan
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Canakis A, Kahaleh M. Endoscopic palliation of malignant biliary obstruction. World J Gastrointest Endosc 2022; 14:581-596. [PMID: 36303806 PMCID: PMC9593514 DOI: 10.4253/wjge.v14.i10.581] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2022] [Revised: 08/20/2022] [Accepted: 10/05/2022] [Indexed: 02/05/2023] Open
Abstract
Malignant biliary obstruction often presents with challenges requiring the endoscopist to assess the location of the lesion, the staging of the disease, the eventual resectability and patient preferences in term of biliary decompression. This review will focus on the different modalities available in order to offer the most appropriate palliation, such as conventional endoscopic retrograde cholangiopancreatography, endoscopic ultrasound guided biliary drainage as well as ablative therapies including photodynamic therapy or radiofrequency ablation.
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Affiliation(s)
- Andrew Canakis
- Department of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD 21201, United States
| | - Michel Kahaleh
- Department of Gastroenterology and Hepatology, Robert Wood Johnson Medical Center, New Brunswick, NJ 08901, United States
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Yang HY, Wang D, Lin X, Han C, Lv YW, Huang RQ, Zhang J, Li ZS, Liao Z, Hu LH. Global trends of ERCP research in the last 25 years: A bibliometrics study. Medicine (Baltimore) 2022; 101:e29454. [PMID: 35945763 PMCID: PMC9351858 DOI: 10.1097/md.0000000000029454] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
PURPOSE Endoscopic retrograde cholangiopancreatography (ERCP) has been used in clinical practice for over 50 years. This study aims to investigate the current state of research in the field of ERCP. METHODS Web of Science database was searched using the term "ERCP" for articles published between 1994 and 2018. The total number of articles from the top 20 countries with the most published articles was determined. The top 5 countries were compared in terms of output per capita, number of articles published in top journals, cumulative impact factor (IF), and average IF. All annual data were subjected to time-trend analysis. The frequently used terms in the titles and abstracts of all articles were retrieved to conduct co-occurrence analysis to determine the research focus of ERCP. RESULTS A total of 9960 articles on ERCP were published between 1994 and 2018, of which 8778 articles were from the top 20 producing countries. There was a significant positive correlation between the output and GDP of each country (R = 0.870, P = .001). The United States of America (USA), Japan, Germany, Italy, and China were the top 5 producing countries with 3190 (32.0%), 868 (8.7%), 658 (6.6%), 512 (5.1%) and 488 (4.9%) articles published, respectively. The USA, Japan, Italy, and China were trending upwards in the total outputs and outputs per capita, while Germany were trending downwards. For average IF, Germany had a downwards trend, while the other 4 countries remained stable. Overall, the USA had the highest output per capita (97.5/10 million) and the highest average IF (6.454). China had the lowest output per capita (3.5/10 million) and average IF (3.125). The ERCP procedures for sphincter of Oddi dysfunction, the combination of ERCP, and laparoscopic cholecystectomy have been the research focus of ERCP. CONCLUSIONS Except for Germany, research on ERCP will continue to increase in the top-producing countries. The outputs per capita and quality of articles from developed countries are higher than those from developing countries.
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Affiliation(s)
- Huai-Yu Yang
- Department of Gastroenterology, Changhai Hospital, The Second Military Medical University, Shanghai, China
| | - Dan Wang
- Department of Gastroenterology, Changhai Hospital, The Second Military Medical University, Shanghai, China
| | - Xi Lin
- Department of Gastroenterology, Changhai Hospital, The Second Military Medical University, Shanghai, China
| | - Chao Han
- Department of Gastroenterology, Changhai Hospital, The Second Military Medical University, Shanghai, China
| | - Yan-Wei Lv
- Department of Gastroenterology, Changhai Hospital, The Second Military Medical University, Shanghai, China
| | - Ren-Qian Huang
- Department of Gastroenterology, Changhai Hospital, The Second Military Medical University, Shanghai, China
| | - Jie Zhang
- Department of Gastroenterology, Changhai Hospital, The Second Military Medical University, Shanghai, China
| | - Zhao-Shen Li
- Department of Gastroenterology, Changhai Hospital, The Second Military Medical University, Shanghai, China
| | - Zhuan Liao
- Department of Gastroenterology, Changhai Hospital, The Second Military Medical University, Shanghai, China
- *Correspondence: Zhuan Liao or Liang-Hao Hu, Department of Gastroenterology, Changhai Hospital, The Second Military Medical University, 168 Changhai Road, Shanghai, China (e-mail: or )
| | - Liang-Hao Hu
- Department of Gastroenterology, Changhai Hospital, The Second Military Medical University, Shanghai, China
- *Correspondence: Zhuan Liao or Liang-Hao Hu, Department of Gastroenterology, Changhai Hospital, The Second Military Medical University, 168 Changhai Road, Shanghai, China (e-mail: or )
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Mohammad T, Kahaleh M. Comparing palliative treatment options for cholangiocarcinoma: photodynamic therapy vs. radiofrequency ablation. Clin Endosc 2022; 55:347-354. [PMID: 35578751 PMCID: PMC9178148 DOI: 10.5946/ce.2021.274] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2020] [Accepted: 01/06/2022] [Indexed: 11/24/2022] Open
Abstract
Referral to an endoscopist is often done once curative resection is no longer an option for cholangiocarcinoma management. In such cases, palliation has become the main objective of the treatment. Photodynamic therapy and radiofrequency ablation can be performed to achieve palliation, with both procedures associated with improved stent patency and survival. Despite the greatly increased cost and association with photosensitivity, photodynamic therapy allows transmission to the entire biliary tree. In contrast, radiofrequency ablation is cheaper and faster to apply, but requires intraductal contact. This paper reviews both modalities and compares their efficacy and safety for bile duct cancer palliation.
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Affiliation(s)
- Tayyaba Mohammad
- Division of Gastroenterology and Hepatology, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA
| | - Michel Kahaleh
- Division of Gastroenterology and Hepatology, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA
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Mohan BP, Chandan S, Khan SR, Kassab LL, Ponnada S, Artifon ELA, Otoch JP, McDonough S, Adler DG. Photodynamic Therapy (PDT), Radiofrequency Ablation (RFA) With Biliary Stents in Palliative Treatment of Unresectable Extrahepatic Cholangiocarcinoma: A Systematic Review and Meta-analysis. J Clin Gastroenterol 2022; 56:e153-e160. [PMID: 33780214 DOI: 10.1097/mcg.0000000000001524] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Accepted: 01/29/2021] [Indexed: 12/27/2022]
Abstract
BACKGROUND AND AIM Extrahepatic unresectable cholangiocarcinoma carries a dismal prognosis. In addition to biliary drainage by stent placement; photodynamic therapy (PDT) and radiofrequency ablation (RFA) have been tried to prolong survival. In this meta-analysis, we appraise the current known data on the use of PDT, RFA in the palliative treatment of extrahepatic unresectable cholangiocarcinoma. METHODS We searched multiple databases from inception through July 2020 to identify studies that reported on PDT and RFA. Pooled rates of survival, stent patency, 30-, 90-day mortality, and adverse events were calculated. Study heterogeneity was assessed using I2% and 95% prediction interval. RESULTS A total of 55 studies (2146 patients) were included. A total of 1149 patients underwent treatment with PDT (33 studies), 545 with RFA (22 studies), and 452 patients with stent-only strategy. The pooled survival rate with PDT, RFA, and stent-only groups was 11.9 [95% confidence interval (CI): 10.7-13.1] months, 8.1 (95% CI: 6.4-9.9) months, and 6.7 (95% CI: 4.9-8.4) months, respectively. The pooled time of stent patency with PDT, RFA, and stent-only groups was 6.1 (95% CI: 4.2-8) months, 5.5 (95% CI: 4.2-6.7) months, and 4.7 (95% CI: 2.6-6.7) months, respectively. The pooled rate of 30-day mortality with PDT was 3.3% (95% CI: 1.6%-6.7%), with RFA was 7% (95% CI: 4.1%-11.7%) and with stent-only was 4.9% (95% CI: 1.7%-13.1%). The pooled rate of 90-day mortality with PDT was 10.4% (95% CI: 5.4%-19.2%) and with RFA was 16.3% (95% CI: 8.7%-28.6%). CONCLUSION PDT seemed to demonstrate better overall survival and 30-day mortality rates than RFA and/or stent-only palliation.
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Affiliation(s)
- Babu P Mohan
- Division of Gastroenterology and Hepatology, University of Utah School of Medicine, Salt Lake City, UT
| | - Saurabh Chandan
- Department of Gastroenterology and Hepatology, CHI-Creighton University Medical Center, Omaha, NE
| | - Shahab R Khan
- Section of Gastroenterology, Rush University Medical Center, Chicago, IL
| | - Lena L Kassab
- Department of Internal Medicine, Mayo Clinic, Rochester, MN
| | - Suresh Ponnada
- Department of Internal Medicine, Carilion Roanoke Memorial Hospital, Roanoke, VA
| | - Everson L A Artifon
- Gastrointestinal Endoscopy Unit, Hospital Das Clinicas, University of Sao Paulo, Sao Paulo, Brazil
| | - Jose P Otoch
- Gastrointestinal Endoscopy Unit, Hospital Das Clinicas, University of Sao Paulo, Sao Paulo, Brazil
| | - Stephanie McDonough
- Division of Gastroenterology and Hepatology, University of Utah School of Medicine, Salt Lake City, UT
| | - Douglas G Adler
- Division of Gastroenterology and Hepatology, University of Utah School of Medicine, Salt Lake City, UT
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Chen P, Yang T, Shi P, Shen J, Feng Q, Su J. Benefits and safety of photodynamic therapy in patients with hilar cholangiocarcinoma: A meta-analysis. Photodiagnosis Photodyn Ther 2022; 37:102712. [PMID: 34995788 DOI: 10.1016/j.pdpdt.2022.102712] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Revised: 12/16/2021] [Accepted: 01/03/2022] [Indexed: 12/25/2022]
Abstract
BACKGROUND Photodynamic therapy (PDT) is a therapy evaluated for the treatment of cancers resistant to standard oncological treatments. PDT might be beneficial for the palliation of hilar cholangiocarcinoma. AIM To evaluate the efficacy and safety of PDT for treating hilar cholangiocarcinoma. METHODS PubMed, Embase, the Cochrane Library, and Web of Science were searched for articles published up to May 2021. The patients were grouped as PDT+stent vs. stent alone. The outcomes were survival, quality of life, and adverse events (AEs). Data were summarized using hazard ratios (HRs), odds ratios (ORs), and 95% confidence intervals (CIs). RESULTS Six studies were included in this meta-analysis. There were 235 and 211 patients in the PDT+stent and stent groups, respectively. The 1-year survival rate of the PDT+stent group was 0.56, and that of the control group was 0.25. The 2-year survival rate of the PDT+stent group was 0.16, and that of the control group was 0.07. PDT significantly prolonged overall survival compared to the controls (P = 0.002). No differences were detected in the occurrence of cholangitis (P = 0.996) and all other AEs (early complications, stent malfunction, total AEs, acute pancreatitis, liver abscess, and biliary hemorrhage) between the two groups. CONCLUSION PDT in patients with hilar cholangiocarcinoma could improve survival without additional AEs. Large-scale randomized controlled trials are needed to confirm the findings.
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Affiliation(s)
- Pengcheng Chen
- Department of General Surgery, Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, Shanghai, China
| | - Ting Yang
- Department of General Surgery, Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, Shanghai, China
| | - Peidong Shi
- Department of General Surgery, Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, Shanghai, China
| | - Jiangbo Shen
- Department of General Surgery, Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, Shanghai, China
| | - Qingchun Feng
- Department of General Surgery, Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, Shanghai, China
| | - Jingen Su
- Department of General Surgery, Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, Shanghai, China.
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Zhao Y, Liu X, Liu X, Yu J, Bai X, Wu X, Guo X, Liu Z, Liu X. Combination of phototherapy with immune checkpoint blockade: Theory and practice in cancer. Front Immunol 2022; 13:955920. [PMID: 36119019 PMCID: PMC9478587 DOI: 10.3389/fimmu.2022.955920] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2022] [Accepted: 08/19/2022] [Indexed: 12/21/2022] Open
Abstract
Immune checkpoint blockade (ICB) therapy has evolved as a revolutionized therapeutic modality to eradicate tumor cells by releasing the brake of the antitumor immune response. However, only a subset of patients could benefit from ICB treatment currently. Phototherapy usually includes photothermal therapy (PTT) and photodynamic therapy (PDT). PTT exerts a local therapeutic effect by using photothermal agents to generate heat upon laser irradiation. PDT utilizes irradiated photosensitizers with a laser to produce reactive oxygen species to kill the target cells. Both PTT and PDT can induce immunogenic cell death in tumors to activate antigen-presenting cells and promote T cell infiltration. Therefore, combining ICB treatment with PTT/PDT can enhance the antitumor immune response and prevent tumor metastases and recurrence. In this review, we summarized the mechanism of phototherapy in cancer immunotherapy and discussed the recent advances in the development of phototherapy combined with ICB therapy to treat malignant tumors. Moreover, we also outlined the significant progress of phototherapy combined with targeted therapy or chemotherapy to improve ICB in preclinical and clinical studies. Finally, we analyzed the current challenges of this novel combination treatment regimen. We believe that the next-generation technology breakthrough in cancer treatment may come from this combinational win-win strategy of photoimmunotherapy.
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Affiliation(s)
- Yujie Zhao
- Laboratory of Integrative Medicine, Clinical Research Center for Breast, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Xu Liu
- Laboratory of Integrative Medicine, Clinical Research Center for Breast, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.,Department of Head, Neck and Mammary Gland Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Xinyu Liu
- Laboratory of Integrative Medicine, Clinical Research Center for Breast, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Jing Yu
- Laboratory of Integrative Medicine, Clinical Research Center for Breast, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Xin Bai
- Laboratory of Integrative Medicine, Clinical Research Center for Breast, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Xi Wu
- Laboratory of Integrative Medicine, Clinical Research Center for Breast, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Xinyu Guo
- Laboratory of Integrative Medicine, Clinical Research Center for Breast, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Zhihui Liu
- Laboratory of Integrative Medicine, Clinical Research Center for Breast, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Xiaowei Liu
- Laboratory of Integrative Medicine, Clinical Research Center for Breast, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
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John ES, Tarnasky PR, Kedia P. Ablative therapies of the biliary tree. Transl Gastroenterol Hepatol 2021; 6:63. [PMID: 34805585 DOI: 10.21037/tgh.2020.02.03] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2019] [Accepted: 01/23/2020] [Indexed: 01/04/2023] Open
Abstract
Cholangiocarcinoma, a malignancy of the epithelial cells in the intrahepatic or extrahepatic biliary tree, is often diagnosed at later stages. Median survival duration ranges from 3 to 9 months with a less than ten percent 5-year survival rate. Thus, often treatment strategies are aimed more towards palliation instead of cure. With the majority of patients presenting with unresectable disease at the time of diagnosis, surgical intervention is not feasible, making less invasive endoscopic therapies more suitable. Initially, biliary stents were utilized for biliary decompression to mitigate cholestatic symptoms and prevent cholangitis; however, this strategy did not prove to provide significant survival benefit. Therefore, efforts to treat the tumor burden itself in addition to maintaining biliary patency became a focus of innovation and research in the endoscopic field. This study has led to the advent of therapies such as photodynamic therapy, radiofrequency ablation, and intraluminal brachytherapy. These options combined with biliary stenting have shown to not only offer the benefit of biliary decompression, but also to potentially improve stent patency and survival. Further, there is an anti-tumor effect of each of these modalities, portending an additional benefit in this subset of patients. Despite numerous retrospective and prospective studies assessing these ablative therapies, there is still a paucity of appropriately powered randomized controlled trials, and further research has yet to be done in the field. This review details the current literature entailing endobiliary ablative strategies.
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Affiliation(s)
- Elizabeth S John
- Department of Gastroenterology, Methodist Dallas Medical Center, Dallas, TX, USA
| | - Paul R Tarnasky
- Department of Gastroenterology, Methodist Dallas Medical Center, Dallas, TX, USA
| | - Prashant Kedia
- Department of Gastroenterology, Methodist Dallas Medical Center, Dallas, TX, USA
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15
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Lu J, Ni C, Huang J, Liu Y, Tao Y, Hu P, Wang Y, Zheng S, Shi M. Biocompatible Mesoporous Silica-Polydopamine Nanocomplexes as MR/Fluorescence Imaging Agent for Light-Activated Photothermal-Photodynamic Cancer Therapy In Vivo. Front Bioeng Biotechnol 2021; 9:752982. [PMID: 34858959 PMCID: PMC8630682 DOI: 10.3389/fbioe.2021.752982] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Accepted: 10/13/2021] [Indexed: 11/13/2022] Open
Abstract
Conventional cancer phototherapy with single modality suffers from low therapeutic efficacy and undesired posttreatment damage for adjacent normal tissues. Therefore, the lower NIR laser irradiation power is vital to the reduction or preclusion of risk of scalds and burns in normal tissues. Herein, we rationally proposed a novel multifunctional nanocomplex, which enabled good magnetic resonance (MR) imaging contrast effect and promising photothermal conversion efficacy. The prepared core/shell nanocomplexes [MSN-Ce6@PDA (Mn)] were composed of chlorin e6-embedded mesoporous silica/nanoparticle composites as the cores, and then polydopamine and manganese ions were conjugated on the cores to form protective shells. The MSN-Ce6@PDA (Mn) nanocomplexes revealed superior properties in colloidal stability, photothermal conversion, reaction oxygen species generation, magnetic resonance imaging, etc. Under the guidance of MR and fluorescence imaging, these MSN-Ce6@PDA (Mn) nanocomplexes were found to be primarily accumulated in the MDA-MB-231 tumor area. Furthermore, the combined photodynamic and photothermal therapy exhibited strong inhibition to the growth of MDA-MB-231 tumor in vitro and in vivo. Besides, the MSN-Ce6@PDA (Mn) nanocomplexes also exhibited excellent biocompatibility and low damage to the healthy animals. Hence, the results demonstrated that the prepared MSN-Ce6@PDA (Mn) nanocomplex would be a promising potential for multimodal imaging-guided phototherapy.
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Affiliation(s)
- Jiahui Lu
- School of Medical Imaging, Xuzhou Medical University, Xuzhou, China
- School of Medical Imaging, Hangzhou Medical College, Hangzhou, China
| | - Chen Ni
- School of Medical Imaging, Xuzhou Medical University, Xuzhou, China
| | - Jie Huang
- School of Medical Imaging, Xuzhou Medical University, Xuzhou, China
| | - Yawen Liu
- School of Medical Imaging, Xuzhou Medical University, Xuzhou, China
| | - Yingkai Tao
- Department of Dermatology and Venereal Diseases, The First People’s Hospital of Changzhou, Changzhou, China
| | - Pengcheng Hu
- School of Medical Imaging, Xuzhou Medical University, Xuzhou, China
| | - Yong Wang
- School of Medical Imaging, Xuzhou Medical University, Xuzhou, China
| | - Shaohui Zheng
- School of Medical Imaging, Xuzhou Medical University, Xuzhou, China
- Institute of Medical Imaging and Digital Medicine, Xuzhou Medical University, Xuzhou, China
| | - Meilin Shi
- School of Medical Imaging, Xuzhou Medical University, Xuzhou, China
- Institute of Medical Imaging and Digital Medicine, Xuzhou Medical University, Xuzhou, China
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16
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Zhu BY, Chen DK, Yin HH, Xia FF, Han XQ. Irradiation stent insertion for distal biliary obstruction secondary to primary common biliary cancer. MINIM INVASIV THER 2021; 31:747-752. [PMID: 33719842 DOI: 10.1080/13645706.2021.1893751] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
PURPOSE To assess the effectiveness and safety of irradiation stent insertion for patients with distal biliary obstruction (DBO) secondary to primary common biliary cancer. MATERIAL AND METHODS Eighty-two consecutive patients with DBO secondary to primary common biliary cancer were treated via either normal (n = 45) or irradiation stenting (n = 37) between January 2013 and December 2019. The instant and long-term outcomes were compared. RESULTS Technical success rates of normal and irradiation stenting were both 100%. Clinical success rates of normal and irradiation stenting were 91.1 and 100%, respectively (p = .179). Stent reobstruction was observed in 13 and 7 patients in the normal and irradiation stenting groups, respectively (p = .295). The median stent patency was 162 and 225 days in the normal and irradiation stenting groups, respectively (p < .001). The median survival was 178 and 250 days in the normal and irradiation stenting groups, respectively (p < .001). Cholangitis was, respectively, observed in 8 and 12 patients in normal and irradiation stenting groups (p = .124). CONCLUSION Irradiation stenting is effective and safe for patients with DBO secondary to primary common biliary cancer and can prolong stent patency and survival.
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Affiliation(s)
- Bing-Yan Zhu
- Department of Radiology, Binzhou People's Hospital, Binzhou, China
| | - Dong-Kai Chen
- Department of Radiology, Binzhou People's Hospital, Binzhou, China
| | - Hong-Hua Yin
- Department of Obstetrics, Binzhou People's Hospital, Binzhou, China
| | - Feng-Fei Xia
- Department of Interventional Vascular Surgery, Binzhou People's Hospital, Binzhou, China
| | - Xin-Qiang Han
- Department of Interventional Vascular Surgery, Affiliated Hospital of Binzhou Medical College, Binzhou, China
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17
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Clinical development and potential of photothermal and photodynamic therapies for cancer. Nat Rev Clin Oncol 2020; 17:657-674. [DOI: 10.1038/s41571-020-0410-2] [Citation(s) in RCA: 723] [Impact Index Per Article: 144.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/17/2020] [Indexed: 02/07/2023]
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18
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Efficacy and safety of palliative endobiliary radiofrequency ablation using a novel temperature-controlled catheter for malignant biliary stricture: a single-center prospective randomized phase II TRIAL. Surg Endosc 2020; 35:63-73. [PMID: 32488654 DOI: 10.1007/s00464-020-07689-z] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2020] [Accepted: 05/27/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND Endobiliary radiofrequency ablation (EB-RFA) has emerged as a palliative treatment for malignant biliary strictures (MBSs); however, concerns about complications related to thermal injury remain. In this study, we evaluated the efficacy and safety of EB-RFA with a novel catheter for MBS. METHODS Patients with inoperable cancer causing MBS were randomly assigned to either the radiofrequency ablation (RFA) group or the non-RFA group. The RFA group underwent EB-RFA at the stricture site with a temperature-controlled catheter (ELRA™; STARmed Co., Goyang, Korea) followed by deployment of a self-expanding metal stent (SEMS). For the non-RFA group, only SEMS placement was performed. The duration of stent patency, overall survival (OS), and 30-day complication rate were evaluated. This trial was registered at ClinicalTrials.gov (number NCT02646514). RESULTS A total of 48 patients were enrolled (24 in each group). During a median follow-up period of 135.0 days (RFA group) and 119.5 days (non-RFA group), the 90-day stent patency rate, median duration of stent patency, and median OS were not different between the groups (58.3% vs. 45.8% [P = 0.386], 132.0 days vs. 116.0 days [P = 0.440], and 244.0 days vs. 180.0 days [P = 0.281], respectively). In the RFA group, procedure-related complications including thermal injury-related complications, such as bile duct perforation or hemobilia, were not reported. The early complication (< 7 days) rates were not different between the groups (4.2% vs. 12.5%, P = 0.609), and there were no late complications (7-30 days) in both groups. CONCLUSION EB-RFA with a temperature-controlled catheter followed by SEMS placement for patients with inoperable MBS can be safe and feasible with acceptable biliary patency.
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19
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Abstract
Endoscopic and percutaneous therapies have been shown to prolong life and reduce morbidity for patients with unresectable advanced stages of primary hepatobiliary malignancies. This article reviews pertinent studies published within the last 5 years that involve locoregional techniques to manage hepatocellular carcinoma, perihilar and distal cholangiocarcinoma. A major emphasis is placed on photodynamic therapy, radiofrequency ablation, irreversible electroporation, and microwave ablation. Technical advances, combinational therapies, and postintervention outcomes are discussed. Despite widespread application, high-quality evidence does not show superiority of any particular locoregional technique for treating advanced hepatobiliary cancers.
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20
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Tringali A. Endoscopic Management in Malignant Biliary Strictures: Tips and Tricks. ENDOTHERAPY IN BILIOPANCREATIC DISEASES: ERCP MEETS EUS 2020:431-461. [DOI: 10.1007/978-3-030-42569-2_40] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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21
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Buerlein RCD, Wang AY. Endoscopic Retrograde Cholangiopancreatography-Guided Ablation for Cholangiocarcinoma. Gastrointest Endosc Clin N Am 2019; 29:351-367. [PMID: 30846158 DOI: 10.1016/j.giec.2018.11.006] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Most patients with perihilar cholangiocarcinoma present with surgically unresectable disease owing to the insidious nature of this malignancy. Relief of malignant perihilar biliary obstruction is a key aspect of cholangiocarcinoma. Although palliative stenting using uncovered metal stents has been advocated in patients with unresectable malignant perihilar biliary strictures, several endoscopic retrograde cholangiopancreatography-guided ablative modalities have emerged. Palliative photodynamic therapy, radiofrequency ablation, and intraluminal brachytherapy have been associated with improved stent patency and survival, although the ideal treatment approach remains unclear. This article reviews the published evidence for using each of these endobiliary ablative modalities in this difficult-to-treat patient population.
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Affiliation(s)
- Ross C D Buerlein
- Division of Gastroenterology and Hepatology, University of Virginia, PO Box 800708, Charlottesville, VA 22908, USA
| | - Andrew Y Wang
- Division of Gastroenterology and Hepatology, University of Virginia, PO Box 800708, Charlottesville, VA 22908, USA.
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22
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Martin EK, Bhutiani N, Egger ME, Philips P, Scoggins CR, McMasters KM, Kelly LR, Vitale GC, Martin RCG. Safety and efficacy of irreversible electroporation in the treatment of obstructive jaundice in advanced hilar cholangiocarcinoma. HPB (Oxford) 2018; 20:1092-1097. [PMID: 30057125 DOI: 10.1016/j.hpb.2018.06.1806] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2018] [Revised: 06/20/2018] [Accepted: 06/23/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND Irreversible electroporation (IRE) has successfully been used for palliation of pancreatic and liver cancers due to its ability to ablate tumors without destroying nearby vital structures. To date, it has not been evaluated in patients with advanced hilar cholangiocarcinoma (AHC). This study presents a single-institution experience with IRE for management of obstructive jaundice in AHC. METHODS A single-institution database was queried for patients undergoing IRE for AHC after PTBD placement for relief of obstructive jaundice from 2010 to 2017 and compared to a control group treated with standard of care only (No IRE). RESULTS Twenty-six patients underwent IRE for AHC after PTBD replacement. Three patients experienced complications, with two experiencing severe (≥ grade 3) complications. After IRE, median time to PTBD removal was 122 days (range 0-305 days) and median catheter-free time before requiring PTBD replacement was 305 days (range 92-458 days). In comparison, the 137 control patients had an admission rate of 59% (N = 80 patients) for PTBD infection, occlusion, or catheter related problem. CONCLUSION IRE safely achieves biliary decompression via tumor electroporation and allows PTBD removal for an extended period of time. In appropriately selected patients with obstructive jaundice in the setting of AHC, IRE can be used to increase catheter-free days and optimize overall quality of life.
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Affiliation(s)
- Emily K Martin
- Department of Surgery, Division of Surgical Oncology, University of Louisville, Louisville, KY, USA
| | - Neal Bhutiani
- Department of Surgery, Division of Surgical Oncology, University of Louisville, Louisville, KY, USA
| | - Michael E Egger
- Department of Surgery, Division of Surgical Oncology, University of Louisville, Louisville, KY, USA
| | - Prejesh Philips
- Department of Surgery, Division of Surgical Oncology, University of Louisville, Louisville, KY, USA
| | - Charles R Scoggins
- Department of Surgery, Division of Surgical Oncology, University of Louisville, Louisville, KY, USA
| | - Kelly M McMasters
- Department of Surgery, Division of Surgical Oncology, University of Louisville, Louisville, KY, USA
| | | | - Gary C Vitale
- Department of Surgery, Division of Surgical Oncology, University of Louisville, Louisville, KY, USA
| | - Robert C G Martin
- Department of Surgery, Division of Surgical Oncology, University of Louisville, Louisville, KY, USA.
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Zhang X, Mo R, Zhao H, Luo X, Yang Y. WITHDRAWN: A comparative effectiveness meta-analysis of photodynamic therapy and stent drainage for unresectable cholangiocarcinoma. Photodiagnosis Photodyn Ther 2018:S1572-1000(18)30085-1. [PMID: 30056241 DOI: 10.1016/j.pdpdt.2018.06.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2018] [Revised: 05/13/2018] [Accepted: 06/22/2018] [Indexed: 02/07/2023]
Abstract
This article has been withdrawn at the request of the author(s) and Editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.
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Affiliation(s)
- Xingwei Zhang
- Institute of Digestive Diseases, Chinese PLA General Hospital, Chinese PLA Medical Academy, Beijing, 100853, China; Medical College of Nankai University, Tianjin, 300071, China
| | - Rui Mo
- Institute of Digestive Diseases, Chinese PLA General Hospital, Chinese PLA Medical Academy, Beijing, 100853, China; Medical College of Nankai University, Tianjin, 300071, China
| | - Huijun Zhao
- Institute of Digestive Diseases, Chinese PLA General Hospital, Chinese PLA Medical Academy, Beijing, 100853, China; Medical College of Nankai University, Tianjin, 300071, China
| | - Xi Luo
- Medical College of Nankai University, Tianjin, 300071, China
| | - Yunsheng Yang
- Institute of Digestive Diseases, Chinese PLA General Hospital, Chinese PLA Medical Academy, Beijing, 100853, China; Medical College of Nankai University, Tianjin, 300071, China.
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Schmidt J, Kuzyniak W, Berkholz J, Steinemann G, Ogbodu R, Hoffmann B, Nouailles G, Gürek AG, Nitzsche B, Höpfner M. Novel zinc‑ and silicon‑phthalocyanines as photosensitizers for photodynamic therapy of cholangiocarcinoma. Int J Mol Med 2018; 42:534-546. [PMID: 29693115 DOI: 10.3892/ijmm.2018.3620] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2017] [Accepted: 03/09/2018] [Indexed: 11/05/2022] Open
Abstract
Photodynamic therapy (PDT) has emerged as an effective and minimally invasive cancer treatment modality. In the present study, two novel phthalocyanines, tetra‑triethyleneoxysulfonyl substituted zinc phthalocyanine (ZnPc) and dihydroxy‑2,9(10),16(17),23(24)‑tetrakis(4,7,10‑trioxaundecan‑1‑sulfonyl) silicon phthalocyanine (Pc32), were investigated as photosensitizers (PS) for PDT of cholangiocarcinoma (CC). ZnPc showed a pronounced dose‑dependent and predominantly cytoplasmic accumulation in EGI‑1 and TFK‑1 CC cell lines. Pc32 also accumulated in the CC cells, but this was less pronounced. Without photoactivation, the PS did not exhibit any antiproliferative or cytotoxic effects. Upon photoactivation, ZnPc induced the formation of reactive oxygen species (ROS) and immediate phototoxicity, leading to a dose‑dependent decrease in cell proliferation, and an induction of mitochondria‑driven apoptosis and cell cycle arrest of EGI‑1 and TFK‑1 cells. Although photoactivated Pc32 also induced ROS formation in the two cell lines, the extent was less marked, compared with that induced by ZnPc‑PDT, and pronounced antipoliferative effects occurred only in the less differentiated EGI‑1 cells, whereas the more differentiated TFK‑1 cells did not show sustained growth inhibition upon Pc32‑PDT induction. In vivo examinations on the antiangiogenic potency of the novel PS were performed using chorioallantoic membrane (CAM) assays, which revealed reduced angiogenic sprouting with a concomitant increase in nonperfused regions and degeneration of the vascular network of the CAM following induction with ZnPc‑PDT only. The study demonstrated the pronounced antiproliferative and antiangiogenic potency of ZnPc as a novel PS for PDT, meriting further elucidation as a promising PS for the photodynamic treatment of CC.
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Affiliation(s)
- Jacob Schmidt
- Institute of Physiology, Charité‑Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‑Universität zu Berlin, and Berlin Institute of Health, D‑10117 Berlin, Germany
| | - Weronika Kuzyniak
- Institute of Physiology, Charité‑Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‑Universität zu Berlin, and Berlin Institute of Health, D‑10117 Berlin, Germany
| | - Janine Berkholz
- Institute of Physiology, Charité‑Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‑Universität zu Berlin, and Berlin Institute of Health, D‑10117 Berlin, Germany
| | - Gustav Steinemann
- Institute of Physiology, Charité‑Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‑Universität zu Berlin, and Berlin Institute of Health, D‑10117 Berlin, Germany
| | - Racheal Ogbodu
- Institute of Physiology, Charité‑Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‑Universität zu Berlin, and Berlin Institute of Health, D‑10117 Berlin, Germany
| | - Björn Hoffmann
- Institute of Physiology, Charité‑Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‑Universität zu Berlin, and Berlin Institute of Health, D‑10117 Berlin, Germany
| | - Geraldine Nouailles
- Department of Infectious Diseases and Pulmonary Medicine, Charité‑Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‑Universität zu Berlin, and Berlin Institute of Health, D‑10117 Berlin, Germany
| | - Ayşe Gül Gürek
- Department of Chemistry, Gebze Technical University, Gebze, Kocaeli 41400, Turkey
| | - Bianca Nitzsche
- Institute of Physiology, Charité‑Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‑Universität zu Berlin, and Berlin Institute of Health, D‑10117 Berlin, Germany
| | - Michael Höpfner
- Institute of Physiology, Charité‑Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt‑Universität zu Berlin, and Berlin Institute of Health, D‑10117 Berlin, Germany
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Abstract
Cholangiocarcinomas (CC) are rare tumors which usually present late and are often difficult to diagnose and treat. CCs are categorized as intrahepatic, hilar, or extrahepatic. Epidemiologic studies suggest that the incidence of intrahepatic CCs may be increasing worldwide. In this chapter, we review the risk factors, clinical presentation, and management of cholangiocarcinoma.
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Affiliation(s)
| | - Andrew Ross
- Virginia Mason Medical Center, Seattle, Washington
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27
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Moole H, Tathireddy H, Dharmapuri S, Moole V, Boddireddy R, Yedama P, Dharmapuri S, Uppu A, Bondalapati N, Duvvuri A. Success of photodynamic therapy in palliating patients with nonresectable cholangiocarcinoma: A systematic review and meta-analysis. World J Gastroenterol 2017; 23:1278-1288. [PMID: 28275308 PMCID: PMC5323453 DOI: 10.3748/wjg.v23.i7.1278] [Citation(s) in RCA: 83] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2016] [Revised: 09/09/2016] [Accepted: 10/10/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To perform a systematic review and meta-analysis on clinical outcomes of photodynamic therapy (PDT) in non-resectable cholangiocarcinoma. METHODS Included studies compared outcomes with photodynamic therapy and biliary stenting (PDT group) vs biliary stenting only (BS group) in palliation of non-resectable cholangiocarcinoma. Articles were searched in MEDLINE, PubMed, and EMBASE. Pooled proportions were calculated using fixed and random effects model. Heterogeneity among studies was assessed using the I2 statistic. RESULTS Ten studies (n = 402) that met inclusion criteria were included in this analysis. The P for χ2 heterogeneity for all the pooled accuracy estimates was > 0.10. Pooled odds ratio for successful biliary drainage (decrease in bilirubin level > 50% within 7days after stenting) in PDT vs BS group was 4.39 (95%CI: 2.35-8.19). Survival period in PDT and BS groups were 413.04 d (95%CI: 349.54-476.54) and 183.41 (95%CI: 136.81-230.02) respectively. The change in Karnofsky performance scores after intervention in PDT and BS groups were +6.99 (95%CI: 4.15-9.82) and -3.93 (95%CI: -8.63-0.77) respectively. Odds ratio for post-intervention cholangitis in PDT vs BS group was 0.57 (95%CI: 0.35-0.94). In PDT group, 10.51% (95%CI: 6.94-14.72) had photosensitivity reactions that were self-limiting. Subgroup analysis of prospective studies showed similar results, except the incidence of cholangitis was comparable in both groups. CONCLUSION In palliation of unresectable cholangiocarcinoma, PDT seems to be significantly superior to BS alone. PDT should be used as an adjunct to biliary stenting in these patients.
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Lee HH, Choi MG, Hasan T. Application of photodynamic therapy in gastrointestinal disorders: an outdated or re-emerging technique? Korean J Intern Med 2017; 32:1-10. [PMID: 28049283 PMCID: PMC5214731 DOI: 10.3904/kjim.2016.200] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2016] [Accepted: 12/19/2016] [Indexed: 01/03/2023] Open
Abstract
Photodynamic therapy (PDT) is a promising therapeutic modality that involves the administration of a photosensitizer followed by local illumination with a specific wavelength of light in the presence of oxygen. PDT is minimally invasive, has high selectivity for cancer, and has good patient compliance due to the simplicity of the procedure; therefore, PDT is widely used as a palliative and salvage treatment in patients with various gastrointestinal malignancies. When used as a salvage treatment for locoregional failures after definitive chemoradiotherapy for esophageal cancer, favorable results have been reported. PDT in conjunction with biliary stenting is a promising palliative treatment for unresectable cholangiocarcinoma, and can be used as an advanced diagnostic and therapeutic strategy in peritoneal dissemination of gastric cancer. Recent clinical reports of PDT for treating non-resectable pancreatic cancer also show promising results. To widen the application of PDT, the integration of PDT with molecular imaging and nanotechnology is being extensively studied. Based on these new developments, PDT is likely to re-emerge as a valuable technique in the treatment of diverse gastrointestinal diseases.
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Affiliation(s)
- Han Hee Lee
- Division of Gastroenterology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Myung-Gyu Choi
- Division of Gastroenterology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Correspondence to Myung-Gyu Choi, M.D. Division of Gastroenterology, Department of Internal Medicine, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Korea Tel: +82-2-2258-2083 Fax: +82-2-2258-2089 E-mail:
| | - Tayyaba Hasan
- Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
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Yang J, Shen H, Jin H, Lou Q, Zhang X. Treatment of unresectable extrahepatic cholangiocarcinoma using hematoporphyrin photodynamic therapy: A prospective study. Photodiagnosis Photodyn Ther 2016; 16:110-118. [PMID: 27720942 DOI: 10.1016/j.pdpdt.2016.10.001] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2016] [Revised: 09/25/2016] [Accepted: 10/04/2016] [Indexed: 02/06/2023]
Abstract
BACKGROUND The available evidence of Photodynamic therapy (PDT) combined with stent placement treatment for unresectable extrahepatic cholangiocarcinoma (EHCC) is still insufficient. It also remains unclear whether PDT influences systemic inflammatory response. AIM To explore the clinical efficacy and safety of the combination treatment and the systemic inflammatory response in patients with EHCC. METHODS Patients with unresectable EHCC underwent either the combined treatment using Hematoporphyrin PDT and stent placement (PDT+stent group, n=12) or stent-only (stent group, n=27). The primary end-point was overall survival. Tumor necrosis factor (TNF)-α and interleukin (IL)-6 levels were measured. Quality of life was assessed using the Karnofsky performance scale (KPS) every 3 months. RESULTS Average survival time (13.8 vs. 9.6 months), and 6-month (91.7% vs. 74.1%), and 1-year (58.3% vs. 3.7%) survival rates of PDT+stent group were significantly increased compared with the stent group. KPS scores in the PDT+stent group were significantly improved. TNF-α and IL-6 levels were significantly increased in the PDT+stent group. CONCLUSION Hematoporphyrin-PDT combined with stent placement is an effective and safe treatment for EHCC. The treatment might promote systemic inflammatory response.
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Affiliation(s)
- Jianfeng Yang
- Department of Gastroenterology, Hangzhou First People's Hospital, Nanjing Medical University, Hangzhou, Zhejiang Province, China
| | - Hongzhang Shen
- Department of Gastroenterology, Hangzhou First People's Hospital, Nanjing Medical University, Hangzhou, Zhejiang Province, China
| | - Hangbin Jin
- Department of Gastroenterology, Hangzhou First People's Hospital, Nanjing Medical University, Hangzhou, Zhejiang Province, China
| | - Qifeng Lou
- Department of Gastroenterology, Hangzhou First People's Hospital, Nanjing Medical University, Hangzhou, Zhejiang Province, China
| | - Xiaofeng Zhang
- Department of Gastroenterology, Hangzhou First People's Hospital, Nanjing Medical University, Hangzhou, Zhejiang Province, China.
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Zheng X, Bo ZY, Wan W, Wu YC, Wang TT, Wu J, Gao DJ, Hu B. Endoscopic radiofrequency ablation may be preferable in the management of malignant biliary obstruction: A systematic review and meta-analysis. J Dig Dis 2016; 17:716-724. [PMID: 27768835 DOI: 10.1111/1751-2980.12429] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2016] [Revised: 09/30/2016] [Accepted: 10/20/2016] [Indexed: 02/07/2023]
Abstract
OBJECTIVE Endoscopic biliary radiofrequency ablation (RFA) has been increasingly used to treat unresectable malignant biliary obstruction (MBO). We aimed to perform this systematic review and meta-analysis to evaluate the efficacy and safety for the treatment of malignant biliary obstruction (MBO) and its impact on patient's survival. METHODS A comprehensive search of the Cochrane Library, PubMed and EMBASE databases was conducted. A meta-analysis was performed by extracting the data from the included studies with regard to technical effectiveness, overall survival, adverse events and mortality of endoscopic RFA. RESULTS A total of nine studies comprising 263 patients with MBO were included in the analysis. There was a significant increase in the diameter of stricture (3.446 mm, 95% confidence interval [CI] 3.356-3.536 mm) after the endoscopic biliary RFA. The overall survival time was 9.62 months, with pooled 30-day, 90-day and 2-year mortality rates of 2% (95% CI 0.5-5.9%), 21% (95% CI 5-37%), and 48% (95% CI 37-59%), respectively. The pooled rate of adverse events was 17% (95% CI 10-25%), and most complications were mild and managed conservatively. Severe adverse events occurred in three patients (two deaths due to hemobilia and one with partial liver infarction). CONCLUSIONS Endoscopic biliary RFA is effective and generally safe in the management of unresectable biliary malignancies, and may improve patients' overall survival. Prospective, randomized controlled studies are required to further support the results.
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Affiliation(s)
- Xiao Zheng
- Department of Endoscopy, Eastern Hepatobiliary Hospital, Second Military Medical University, Shanghai, China
| | - Zhi Yuan Bo
- Department of Endoscopy, Eastern Hepatobiliary Hospital, Second Military Medical University, Shanghai, China
| | - Wei Wan
- Department of Endoscopy, Eastern Hepatobiliary Hospital, Second Military Medical University, Shanghai, China
| | - Ye Chen Wu
- Department of Endoscopy, Eastern Hepatobiliary Hospital, Second Military Medical University, Shanghai, China
| | - Tian Tian Wang
- Department of Endoscopy, Eastern Hepatobiliary Hospital, Second Military Medical University, Shanghai, China
| | - Jun Wu
- Department of Endoscopy, Eastern Hepatobiliary Hospital, Second Military Medical University, Shanghai, China
| | - Dao Jian Gao
- Department of Endoscopy, Eastern Hepatobiliary Hospital, Second Military Medical University, Shanghai, China
| | - Bing Hu
- Department of Endoscopy, Eastern Hepatobiliary Hospital, Second Military Medical University, Shanghai, China
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Lee TY, Cheon YK, Shim CS. Photodynamic Therapy in Patients with Advanced Hilar Cholangiocarcinoma: Percutaneous Cholangioscopic Versus Peroral Transpapillary Approach. Photomed Laser Surg 2016; 34:150-6. [PMID: 26982507 DOI: 10.1089/pho.2015.3989] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
OBJECTIVE This study aimed to compare the clinical outcomes of patients with advanced hilar cholangiocarcinoma (CC) who underwent photodynamic therapy (PDT) with either percutaneous transhepatic cholangioscopy (PTCS) or endoscopic retrograde cholangiopancreatography (ERCP). BACKGROUND DATA PDT has been proposed as a promising therapy for treatment of unresectable hilar CC that is resistant to conventional standard treatment. However, few studies have compared the delivery methods of PDT in unresectable hilar CC patients. METHODS Thirty-seven adult patients with advanced hilar CC were included in this study. Twenty-four patients treated with PTCS-directed PDT and 13 patients treated with ERCP-directed PDT were analyzed retrospectively. RESULTS The PTCS- and ERCP-directed PDT groups were comparable with respect to age, gender, health status, pretreatment bilirubin levels, Bismuth type, and hilar CC stage. The length of hospital stay differed significantly (p < 0.001) between the two groups, with a median hospital stay of 37 days (range, 13-77 days) in the ERCP-directed PDT group versus 63 days (range, 23-125 days) in the PTCS-directed group. PTCS-directed PDT patients demonstrated an overall survival similar to that of ERCP-directed PDT patients, with a median survival of 11.6 versus 9.5 months, respectively (p = 0.96). Only lower pre-PDT bilirubin levels (p = 0.002) were a significant predictor of improved survival in all patients who underwent PDT, as determined by multivariate analysis. Median metal stent patency was similar between the groups [PTCS-directed PDT group (n = 8), 6.2 months; ERCP-directed PDT group (n = 7), 7.2 months; p = 0.642]. Survival after PTCS- or ERCP-directed PDT was not statistically different in patients with advanced hilar CC. CONCLUSIONS Lower pre-PDT bilirubin levels were associated with longer survival in all patients.
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Affiliation(s)
- Tae Yoon Lee
- Digestive Disease Center, Department of Internal Medicine, Konkuk University School of Medicine , Seoul, Korea
| | - Young Koog Cheon
- Digestive Disease Center, Department of Internal Medicine, Konkuk University School of Medicine , Seoul, Korea
| | - Chan Sup Shim
- Digestive Disease Center, Department of Internal Medicine, Konkuk University School of Medicine , Seoul, Korea
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Smith I, Kahaleh M. Biliary Tumor Ablation with Photodynamic Therapy and Radiofrequency Ablation. Gastrointest Endosc Clin N Am 2015; 25:793-804. [PMID: 26431605 DOI: 10.1016/j.giec.2015.06.013] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Within the past two decades, major progress has been made in biliary endoscopy both with stenting and with ablative therapy. A primary goal in patients with malignant biliary lesions who are not candidates for surgery is to provide localized and efficient necrosis of the lesions. This article summarizes the current literature on biliary tumor ablation with photodynamic therapy and radiofrequency ablation. Prognosis, treatment technique, potential complications, treatment efficacy, and controversies are discussed.
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Affiliation(s)
- Ioana Smith
- Division of Gastroenterology and Hepatology, University of Alabama at Birmingham, 1720 2nd Avenue South BDB 380, Birmingham, AL 35294, USA
| | - Michel Kahaleh
- Division of Gastroenterology and Hepatology, Weill Cornell Medical College, 1305 York Avenue 4th floor, New York, NY 10021, USA.
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Uppal DS, Wang AY. Advances in endoscopic retrograde cholangiopancreatography for the treatment of cholangiocarcinoma. World J Gastrointest Endosc 2015; 7:675-687. [PMID: 26140095 PMCID: PMC4482827 DOI: 10.4253/wjge.v7.i7.675] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2014] [Revised: 01/22/2015] [Accepted: 02/11/2015] [Indexed: 02/05/2023] Open
Abstract
Cholangiocarcinoma (CCA) is a malignancy of the bile ducts that carries high morbidity and mortality. Patients with CCA typically present with obstructive jaundice, and associated complications of CCA include cholangitis and biliary sepsis. Endoscopic retrograde cholangiopancreatography (ERCP) is a valuable treatment modality for patients with CCA, as it enables internal drainage of blocked bile ducts and hepatic segments by using plastic or metal stents. While there remains debate as to if bilateral (or multi-segmental) hepatic drainage is required and/or superior to unilateral drainage, the underlying tenant of draining any persistently opacified bile ducts is paramount to good ERCP practice and good clinical outcomes. Endoscopic therapy for malignant biliary strictures from CCA has advanced to include ablative therapies via ERCP-directed photodynamic therapy (PDT) or radiofrequency ablation (RFA). While ERCP techniques cannot cure CCA, advancements in the field of ERCP have enabled us to improve upon the quality of life of patients with inoperable and incurable disease. ERCP-directed PDT has been used in lieu of brachytherapy to provide neoadjuvant local tumor control in patients with CCA who are awaiting liver transplantation. Lastly, mounting evidence suggests that palliative ERCP-directed PDT, and probably ERCP-directed RFA as well, offer a survival advantage to patients with this difficult-to-treat malignancy.
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Madhusudhan KS, Gamanagatti S, Gupta AK. Imaging and interventions in hilar cholangiocarcinoma: A review. World J Radiol 2015; 7:28-44. [PMID: 25729485 PMCID: PMC4326732 DOI: 10.4329/wjr.v7.i2.28] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2014] [Revised: 11/14/2014] [Accepted: 12/16/2014] [Indexed: 02/06/2023] Open
Abstract
Hilar cholangiocarcinoma is a common malignant tumor of the biliary tree. It has poor prognosis with very low 5-year survival rates. Various imaging modalities are available for detection and staging of the hilar cholangiocarcinoma. Although ultrasonography is the initial investigation of choice, imaging with contrast enhanced computed tomography scan or magnetic resonance imaging is needed prior to management. Surgery is curative wherever possible. Radiological interventions play a role in operable patients in the form of biliary drainage and/or portal vein embolization. In inoperable cases, palliative interventions include biliary drainage, biliary stenting and intra-biliary palliative treatment techniques. Complete knowledge of application of various imaging modalities available and about the possible radiological interventions is important for a radiologist to play a critical role in appropriate management of such patients.We review the various imaging techniques and appearances of hilar cholangiocarcinoma and the possible radiological interventions.
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Zheng YG, Wang T, Li F, Cheng ZB. Use of stents in treatment of malignant biliary obstruction. Shijie Huaren Xiaohua Zazhi 2014; 22:5279-5284. [DOI: 10.11569/wcjd.v22.i34.5279] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Stents are now recognized as the first choice of palliative therapy for malignant biliary obstruction. Since stents can effectively relieve obstruction, reduce jaundice, and improve the quality of life, their usage in inoperable biliary tract cancer patients has broad prospects. This paper reviews the use of stents in the treatment of malignant biliary obstruction with regards to stent type, selection, placement and the combination of stenting with other means of treatment.
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Abstract
Cholangiocarcinomas are often locally advanced or have metastasized, and at the time of diagnosis individuals often have a poor prognosis. Endoscopic treatment options traditionally include biliary decompression via stenting to allow for systemic chemotherapy and radiotherapy, with self-expanding metal biliary stents being preferred. Recent developments in locoregional therapy delivered endoscopically, such as photodynamic therapy and radiofrequency abalation, have shown promising results in improving patient survival.
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Affiliation(s)
- Linda Ann Hou
- Division of Gastrointestinal and Liver Diseases, LAC+USC Medical Center, Keck School of Medicine of USC, 1983 Marengo Avenue, D & T Building, Room B4H100, Los Angeles, CA 90033, USA
| | - Jacques Van Dam
- Digestive Health Institute, The Keck Medical Center of USC, 1510 San Pablo Street, Suite 322R, CA, USA
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Mönkemüller K, Popa D, Wilcox CM. Endoscopic treatment options for cholangiocarcinomas. Expert Rev Anticancer Ther 2014; 14:407-418. [PMID: 24506765 DOI: 10.1586/14737140.2014.870480] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Cholangiocellular carcinoma (CCC) is a very aggressive tumor, which remains highly resistant to current chemoradiation therapies. Death is usually caused by the tumor burden. However, biliary obstruction, which leads to cholangitis and liver failure, is also a cause of death. Therefore, relief of biliary obstruction is one of the key palliative treatment options for patients with hilar or distal CCC. Radiologic or endoscopic insertions of stents (plastic or self-expanding metal) are definite biliary drainage options. Whereas stents alone can help achieve relief of bile duct obstruction, endoscopic ablative interventions with photodynamic therapy or radiofrequency ablation are also useful in destroying intraluminal tumor. Destroying the tumor leads to an increase in the luminal diameter of the obstructed bile duct, allowing for placement of more or larger diameter stents, and thus improving bile flow. Besides decreasing morbidity associated with obstruction, ablative therapies such as photodynamic therapy have also been associated with improved survival in a sub-group of patients with CCC and should therefore be incorporated into the treatment algorithm of any center treating patients with CCC.
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Affiliation(s)
- Klaus Mönkemüller
- Basil I. Hirschowitz Endoscopic Center of Excellence, Division of Gastroenterology and Hepatology, University of Alabama at Birmingham, AL 35249, USA
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Shah KN, Clary BM. Endoscopic and Percutaneous Approaches to the Treatment of Biliary Tract and Primary Liver Tumors. Surg Oncol Clin N Am 2014; 23:207-30. [DOI: 10.1016/j.soc.2013.10.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Yu H, Miao L. Biliary stenting for cholangiocarcinoma: An update. Shijie Huaren Xiaohua Zazhi 2014; 22:648-653. [DOI: 10.11569/wcjd.v22.i5.648] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Cholangiocarcinoma (bile duct cancer) is the most common malignant tumor of the biliary tree. This devastating malignancy presents late, and is notoriously difficult to diagnose, thus resulting a high mortality. The majority of cholangiocarcinoma patients present with an unresectable disease, and survive less than 12 mo following diagnosis. Biliary stent placement is an effective palliative therapy for malignant biliary obstruction, which can significantly improve the quality of life, and extend the survival time of patients. Different biliary stent placement methods would closely affect the prognosis of patients. The purpose of this article is to review the treatment efficacy, insertion paths and types of biliary stents. This paper also covers emerging biliary stents including drug stents, and biliary stent combination local therapy.
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Siddiqui A, Shahid H, Sarkar A, Cox K, Kowalski TE, Loren DE, Sharma A, Laing P, Birch M, Adler DG. Stage of hilar cholangiocarcinoma predicts recurrence of biliary obstruction in patients with metal stents. Clin Gastroenterol Hepatol 2013; 11:1169-73. [PMID: 23811239 DOI: 10.1016/j.cgh.2013.05.035] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2013] [Revised: 05/03/2013] [Accepted: 05/28/2013] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Most patients with hilar cholangiocarcinomas present with unresectable tumors, so only palliative biliary drainage with self-expanding metal stents (SEMS) is possible. Stents eventually cease to function because of tumor overgrowth and/or other causes, so it is important to identify factors that affect stent patency and failure. We examined the patency of endoscopically placed SEMS in patients with hilar cholangiocarcinoma and factors associated with patency. METHODS We performed a retrospective study of 120 consecutive patients (mean age, 67 ± 14.6 years; 74 male) who presented with obstructive jaundice from hilar cholangiocarcinoma and underwent bilateral SEMS from September 2006 through April 2012 at 2 US tertiary medical centers. We collected data on patient demographics and survival, success of stent placement and function, and immediate adverse events. The primary outcome was duration of stent patency (time from insertion to failure). RESULTS Thirty-eight patients had stage 1 hilar cholangiocarcinomas, 45 had stage 2, 12 had stage 3, and 25 had stage 4. The median length of the hilar stricture was 9 mm (range, 8-50 mm). The stent was successfully passaged across the stricture in all patients and was functional in 115; its median length was 8 mm (range, 8-10 mm), and diameter was 80 mm (range, 60-100 mm). Fourteen patients had immediate adverse events, including perforation (n = 2), bleeding (n = 2), pancreatitis (n = 9), and cholangitis (n = 1). Median survival was 17 weeks (range, 1-211 weeks), and 50 patients had stent occlusion. On Kaplan-Meier analysis, the median time from stent placement to occlusion was 17 weeks (range, 1-104 weeks). More patients with stage 3 or 4 tumors (64%) had SEMS occlusion than patients with stage 1 or 2 tumors (28%) in univariate analysis (P = .017). In multivariate analysis, only cancer stage was independently and significantly associated with patency (P = .006; hazard ratio, 2.77); age, sex, length of stricture, and SEMS diameter and length were not. CONCLUSIONS The cumulative patency of bilateral SEMS for hilar cholangiocarcinoma significantly decreases as tumor stage increases. Age, sex, length of stricture, and SEMS diameter and length are not associated with SEMS patency.
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Affiliation(s)
- Ali Siddiqui
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, USA
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Ursodeoxycholic acid-conjugated chitosan for photodynamic treatment of HuCC-T1 human cholangiocarcinoma cells. Int J Pharm 2013; 454:74-81. [PMID: 23834828 DOI: 10.1016/j.ijpharm.2013.06.035] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2013] [Revised: 05/27/2013] [Accepted: 06/13/2013] [Indexed: 02/07/2023]
Abstract
Chitosan was hydrophobically modified with ursodeoxycholic acid (UDCA) to fabricate nano-photosensitizer for photodynamic therapy (PDT) of HuCC-T1 cholangiocarcinoma cells. Synthesis of UDCA-conjugated chitosan (ChitoUDCA) was confirmed using (1)H NMR spectra. Chlorin E6 (Ce6) was used as a photosensitizer and incorporated into ChitoUDCA nanoparticles through formation of ion complexes. Morphology of Ce6-incorporated ChitoUDCA nanoparticles was observed using TEM and their shapes were spherical with sizes around 200-400 nm. The PDT potential of Ce6-incorporated ChitoUDCA nanoparticles were studied with HuCC-T1 human cholangiocarcinoma cells. The results showed that ChitoUDCA nanoparticles enhances of Ce6 uptake into tumor cells, phototoxicity, and ROS generation compared to Ce6 itself. Furthermore, Ce6-incorporated ChitoUDCA nanoparticles showed quenching in aqueous solution and sensing at tumor cells. We suggest that Ce6-incorporated ChitoUDCA nanoparticles are promising candidates for PDT of cholangiocarcinoma cells.
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Lee TY, Cheon YK, Shim CS. Current status of photodynamic therapy for bile duct cancer. Clin Endosc 2013; 46:38-44. [PMID: 23423177 PMCID: PMC3572349 DOI: 10.5946/ce.2013.46.1.38] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2012] [Revised: 12/14/2012] [Accepted: 12/14/2012] [Indexed: 12/11/2022] Open
Abstract
The most common form in bile duct cancers is a highly desmoplastic cancer with a growth pattern characterized by periductal extension and infiltration. The prognosis of bile duct cancers, especially hilar cholangiocarcinoma, is limited by tumor spread along the biliary tree leading to refractory obstructive cholestasis, cholangitis, and liver failure. Although biliary endoprosthesis improves occlusion rates and reduces the number of therapeutic interventions, median survival time is not ameliorated. Photodynamic therapy (PDT) is a local photochemical tumor treatment that consists of a photosensitizing agent in combination with laser irradiation of a distinct wavelength. Tumor ablation with PDT combined with biliary stenting reduces cholestasis and significantly improves median survival time in selected patients with bile duct cancers.
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Affiliation(s)
- Tae Yoon Lee
- Digestive Disease Center, Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
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