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Cordista V, Patel S, Lawson R, Lee G, Verheyen M, Westbrook A, Shelton N, Sapkota P, Zabala Valencia I, Gaddam C, Thomas J. Towards a Customizable, SLA 3D-Printed Biliary Stent: Optimizing a Commercially Available Resin and Predicting Stent Behavior with Accurate In Silico Testing. Polymers (Basel) 2024; 16:1978. [PMID: 39065295 PMCID: PMC11280906 DOI: 10.3390/polym16141978] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2024] [Revised: 06/22/2024] [Accepted: 07/02/2024] [Indexed: 07/28/2024] Open
Abstract
Inflammation of the bile ducts and surrounding tissues can impede bile flow from the liver into the intestines. If this occurs, a plastic or self-expanding metal (SEM) stent is placed to restore bile drainage. United States (US) Food and Drug Administration (FDA)-approved plastic biliary stents are less expensive than SEMs but have limited patency and can occlude bile flow if placed spanning a duct juncture. Recently, we investigated the effects of variations to post-processing and autoclaving on a commercially available stereolithography (SLA) resin in an effort to produce a suitable material for use in a biliary stent, an FDA Class II medical device. We tested six variations from the manufacturer's recommended post-processing and found that tripling the isopropanol (IPA) wash time to 60 min and reducing the time and temperature of the UV cure to 10 min at 40 °C, followed by a 30 min gravity autoclave cycle, yielded a polymer that was flexible and non-cytotoxic. In turn, we designed and fabricated customizable, SLA 3D-printed polymeric biliary stents that permit bile flow at a duct juncture and can be deployed via catheter. Next, we generated an in silico stent 3-point bend test to predict displacements and peak stresses in the stent designs. We confirmed our simulation accuracy with experimental data from 3-point bend tests on SLA 3D-printed stents. Unfortunately, our 3-point bend test simulation indicates that, when bent to the degree needed for placement via catheter (~30°), the peak stress the stents are predicted to experience would exceed the yield stress of the polymer. Thus, the risk of permanent deformation or damage during placement via catheter to a stent printed and post-processed as we have described would be significant. Moving forward, we will test alternative resins and post-processing parameters that have increased elasticity but would still be compatible with use in a Class II medical device.
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Affiliation(s)
- Victoria Cordista
- School of Engineering, Mercer University, Macon, GA 31207, USA; (V.C.); (S.P.); (R.L.); (G.L.); (M.V.); (A.W.); (N.S.); (P.S.); (I.Z.V.); (C.G.)
- McKelvey School of Engineering, Washington University, St. Louis, MO 63114, USA
| | - Sagar Patel
- School of Engineering, Mercer University, Macon, GA 31207, USA; (V.C.); (S.P.); (R.L.); (G.L.); (M.V.); (A.W.); (N.S.); (P.S.); (I.Z.V.); (C.G.)
- Medical College of Georgia, Augusta University, Augusta, GA 30912, USA
| | - Rebecca Lawson
- School of Engineering, Mercer University, Macon, GA 31207, USA; (V.C.); (S.P.); (R.L.); (G.L.); (M.V.); (A.W.); (N.S.); (P.S.); (I.Z.V.); (C.G.)
| | - Gunhee Lee
- School of Engineering, Mercer University, Macon, GA 31207, USA; (V.C.); (S.P.); (R.L.); (G.L.); (M.V.); (A.W.); (N.S.); (P.S.); (I.Z.V.); (C.G.)
| | - Morgan Verheyen
- School of Engineering, Mercer University, Macon, GA 31207, USA; (V.C.); (S.P.); (R.L.); (G.L.); (M.V.); (A.W.); (N.S.); (P.S.); (I.Z.V.); (C.G.)
| | - Ainsley Westbrook
- School of Engineering, Mercer University, Macon, GA 31207, USA; (V.C.); (S.P.); (R.L.); (G.L.); (M.V.); (A.W.); (N.S.); (P.S.); (I.Z.V.); (C.G.)
| | - Nathan Shelton
- School of Engineering, Mercer University, Macon, GA 31207, USA; (V.C.); (S.P.); (R.L.); (G.L.); (M.V.); (A.W.); (N.S.); (P.S.); (I.Z.V.); (C.G.)
| | - Prakriti Sapkota
- School of Engineering, Mercer University, Macon, GA 31207, USA; (V.C.); (S.P.); (R.L.); (G.L.); (M.V.); (A.W.); (N.S.); (P.S.); (I.Z.V.); (C.G.)
| | - Isabella Zabala Valencia
- School of Engineering, Mercer University, Macon, GA 31207, USA; (V.C.); (S.P.); (R.L.); (G.L.); (M.V.); (A.W.); (N.S.); (P.S.); (I.Z.V.); (C.G.)
| | - Cynthia Gaddam
- School of Engineering, Mercer University, Macon, GA 31207, USA; (V.C.); (S.P.); (R.L.); (G.L.); (M.V.); (A.W.); (N.S.); (P.S.); (I.Z.V.); (C.G.)
| | - Joanna Thomas
- School of Engineering, Mercer University, Macon, GA 31207, USA; (V.C.); (S.P.); (R.L.); (G.L.); (M.V.); (A.W.); (N.S.); (P.S.); (I.Z.V.); (C.G.)
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Ledenko M, Toskich B, Mehner C, Ceylan H, Patel T. Therapeutic biliary stents: applications and opportunities. Expert Rev Med Devices 2024; 21:399-409. [PMID: 38716580 DOI: 10.1080/17434440.2024.2341960] [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: 01/05/2024] [Accepted: 04/08/2024] [Indexed: 05/31/2024]
Abstract
INTRODUCTION Biliary stents are used to optimize ductal patency and enable bile flow in the management of obstruction or injury related to biliary tract tumors, strictures, stones, or leaks. Although direct therapeutic applications of biliary stents are less well developed, stents can be used to deliver drugs, radioisotopes, and photodynamic therapy. AREAS COVERED This report provides an in-depth overview of the clinical indications, and therapeutic utility of biliary stents. Unique considerations for the design of biliary stents are described. The properties and functionalities of materials used for stents such as metal alloys, plastic polymers, or biodegradable materials are described, and opportunities for design of future stents are outlined. Current and potential applications of stents for therapeutic applications for biliary tract diseases are described. EXPERT OPINION Therapeutic biliary stents could be used to minimize inflammation, prevent stricture formation, reduce infections, or provide localized anti-cancer therapy for biliary tract cancers. Stents could be transformed into therapeutic platforms using advanced materials, 3D printing, nanotechnology, and artificial intelligence. Whilst clinical study and validation will be required for adoption, future advances in stent design and materials are expected to expand the use of therapeutic biliary stents for the treatment of biliary tract disorders.
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Affiliation(s)
- Matthew Ledenko
- Department of Transplantation, Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL, USA
| | - Beau Toskich
- Department of Radiology, Mayo Clinic, Jacksonville, FL, USA
| | - Christine Mehner
- Department of Physiology and Biomedical Engineering, Mayo Clinic, Jacksonville, FL, USA
| | - Hakan Ceylan
- Department of Physiology and Biomedical Engineering, Mayo Clinic, Jacksonville, FL, USA
| | - Tushar Patel
- Department of Transplantation, Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL, USA
- Department of Physiology and Biomedical Engineering, Mayo Clinic, Jacksonville, FL, USA
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Yang K, Sun W, Cui L, Zou Y, Wen C, Zeng R. Advances in functional coatings on biliary stents. Regen Biomater 2024; 11:rbae001. [PMID: 38343880 PMCID: PMC10858350 DOI: 10.1093/rb/rbae001] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2023] [Revised: 12/07/2023] [Accepted: 12/19/2023] [Indexed: 01/03/2025] Open
Abstract
Biliary stenting is an important interventional method for the prevention and treatment of biliary tract diseases. However, complications, such as postoperative biliary infection and restenosis, frequently occur due to the extensive scope of the biliary system and the complex composition of bile. The combination of coating technology and biliary stents is expected to bring new approaches to the solution of these problems. The cutting-edge advance on functional coatings on biliary stents is reviewed from seven perspectives: anticorrosion, -bacterial, -tumor, stone-dissolving, X-ray visibility, antistent migration and functional composite coatings. The development trend is also discussed. Overall, the performance of the numerous functional coatings for various purposes is generally up to expectations, but the balance between the medications' effectiveness and their safety needs to be further adjusted. Many contemporary investigations have advanced to the level of animal experiments, offering crucial fundamental assurance for broader human studies. The combination of biliary stents and functional coatings is an innovative idea with great potential for future development.
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Affiliation(s)
- Kaining Yang
- Department of Bioengineering, College of Chemical and Biological Engineering, Shandong University of Science and Technology, Qingdao 266590, China
| | - Wenxin Sun
- Department of Bioengineering, College of Chemical and Biological Engineering, Shandong University of Science and Technology, Qingdao 266590, China
| | - Lanyue Cui
- Corrosion Laboratory for Light Metals, College of Materials Science and Engineering, Shandong University of Science and Technology, Qingdao 266590, China
| | - Yuhong Zou
- Department of Bioengineering, College of Chemical and Biological Engineering, Shandong University of Science and Technology, Qingdao 266590, China
| | - Cuie Wen
- School of Engineering, RMIT University, Melbourne, VIC 3001, Australia
| | - Rongchang Zeng
- Corrosion Laboratory for Light Metals, College of Materials Science and Engineering, Shandong University of Science and Technology, Qingdao 266590, China
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Song G, Zhao HQ, Liu Q, Fan Z. A review on biodegradable biliary stents: materials and future trends. Bioact Mater 2022; 17:488-495. [PMID: 35415292 PMCID: PMC8968460 DOI: 10.1016/j.bioactmat.2022.01.017] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 12/28/2021] [Accepted: 01/10/2022] [Indexed: 12/12/2022] Open
Abstract
Biliary stricture is defined as the reduction and narrowing of the bile duct lumen, which can be caused by many factors such as cancer and inflammation. Biliary stent placement can effectively alleviate benign and malignant biliary strictures. However, the commonly used plastic or metallic biliary stents are far from ideal and do not satisfy all clinical requirements，although several types of biodegradable biliary stents have been developed and used clinically. In this review, we summarized current development status of biodegradable stents with the emphasis on the stent materials. We also presented the future development trends based on the published literature.
Summary of current development status of bioresorbable biliary stents with the emphasis on the stent materials. The future development trends based on the published literature. The advantages of bioresorbable biliary stents compared with metallic and plastic biliary stents.
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Madhusudhan KS, Jineesh V, Keshava SN. Indian College of Radiology and Imaging Evidence-Based Guidelines for Percutaneous Image-Guided Biliary Procedures. Indian J Radiol Imaging 2021; 31:421-440. [PMID: 34556927 PMCID: PMC8448229 DOI: 10.1055/s-0041-1734222] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/07/2022] Open
Abstract
Percutaneous biliary interventions are among the commonly performed nonvascular radiological interventions. Most common of these interventions is the percutaneous transhepatic biliary drainage for malignant biliary obstruction. Other biliary procedures performed include percutaneous cholecystostomy, biliary stenting, drainage for bile leaks, and various procedures like balloon dilatation, stenting, and large-bore catheter drainage for bilioenteric or post-transplant anastomotic strictures. Although these procedures are being performed for ages, no standard guidelines have been formulated. This article attempts at preparing guidelines for performing various percutaneous image-guided biliary procedures along with discussion on the published evidence in this field.
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Affiliation(s)
| | - Valakkada Jineesh
- Department of Radiology, Sree Chitra Tirunal Institute of Medical Sciences and Technology (Thiruvananthapuram), Kerala, India
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Tian L, Lu Z, Lei L, Yang N, Chen Z, Lu B, Jin Z, Shen Y, Guo S. Preparation, characterization and primary evaluation of trilayered biliary stent films for anti-cholangiocarcinoma and anti-biofilm formation. Int J Pharm 2021; 606:120869. [PMID: 34245845 DOI: 10.1016/j.ijpharm.2021.120869] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Revised: 06/29/2021] [Accepted: 07/05/2021] [Indexed: 11/29/2022]
Abstract
Excessive growth of tumor within biliary wall and formation of biofilm on inner surface of stent can cause restenosis or even obstruction after stent implantation. Therefore, it is important and valuable to develop a new biliary stent for anti-cholangiocarcinoma and anti-biofilm formation. Herein, we designed, prepared and primarily evaluated a new trilayered film for biliary stents consisting of one poly (lactic acid) (PLA) layer loaded with anti-tumor paclitaxel (PTX layer), one middle PLA isolation layer (isolation layer) and one PLA layer loaded with antimicrobial ofloxacin (OFLX layer). It is postulated that the PTX layer releases drug towards biliary wall with tumor, the OFLX layer releases drug towards lumen of bile duct and the isolation layer is used to separate from the PTX layer and the OFLX layer and facilitate drug release in unidirectional way. The prepared trilayered films were characterized in terms of morphology, microstructure, crystallinity and biodegradability. It was found that the films could effectively tune drug release by addition of different amounts of drug or PEG, release PTX and OFLX in opposite directions, effectively inhibit the proliferation of human cholangiocarcinoma RBE cells, the adherence of E. coli and S. aureus and the formation of biofilm in vitro. It is potential that the trilayered films can be used to fabricate a new biliary stent with a dual function of anti-cholangiocarcinoma and anti-biofilm formation.
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Affiliation(s)
- Liu Tian
- School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China
| | - Zhanjun Lu
- Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 85 Wujin Road, Shanghai 200080, China
| | - Lei Lei
- School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China
| | - Ning Yang
- School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China
| | - Zhaoyang Chen
- School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China
| | - Beike Lu
- School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China
| | - Zhu Jin
- School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China
| | - Yuanyuan Shen
- School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China.
| | - Shengrong Guo
- School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China.
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Mohan BP, Canakis A, Khan SR, Chandan S, Ponnada S, McDonough S, Adler DG. Drug Eluting Versus Covered Metal Stents in Malignant Biliary Strictures-Is There a Clinical Benefit?: A Systematic Review and Meta-Analysis. J Clin Gastroenterol 2021; 55:271-277. [PMID: 32554989 DOI: 10.1097/mcg.0000000000001377] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2019] [Accepted: 05/11/2020] [Indexed: 01/11/2023]
Abstract
GOALS/BACKGROUND Patients with malignant biliary obstruction (MBO) often require transpapillary stenting for symptomatic relief and biliary decompression. Plastic stents and uncovered metal stents are now replaced by covered self-expanding metal stents (SEMS). However, stent occlusion from tumor overgrowth and chronic inflammation continues to be an issue. Drug-eluting stents (DES), through an antitumor paclitaxel membrane, have been used to combat this problem. The aim of this study was to conduct a meta-analysis comparing DES to SEMS in MBO. STUDY Multiple databases were searched to identify studies that compared the clinical outcomes of SEMS and DES in patients with MBO. Random-effects model was used to calculate the pooled odds ratio and the pooled individual outcomes. Our primary goals were to assess the stent patency and overall survival in days. Secondary outcomes assessed the individual reported adverse events and/or complications. RESULTS Five studies including 348 patients (175 males and 173 females) were included. The pooled odds ratio of stent patency was 1.03 (95% confidence interval: 0.68-1.54, P=0.9) and overall survival was 1.16 (95% confidence interval: 0.63-2.11, P=0.6). The pooled rate of stent patency was 168.3 (95% 140.7-196.4) days for DES and 149.4 (117.6-181.2) days for SEMS. The pooled rate of overall survival was 267.2 (206.2-328.2) days for DES and 218.2 (148.5-287.8) days for SEMS. CONCLUSION On the basis of this meta-analysis, DES and SEMS seem to demonstrate comparable clinical outcomes in patients with malignant biliary strictures. Reported adverse events and/or complications were comparable as well.
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Affiliation(s)
- Babu P Mohan
- Department of Internal Medicine, Banner University Medical Center, University of Arizona, Tucson, AZ
| | - Andrew Canakis
- Department of Internal Medicine, Boston Medical Center, Boston University School of Medicine, Boston, MA
| | - Shahab R Khan
- Department of Gastroenterology, Rush University Medical Center, Chicago, IL
| | - Saurabh Chandan
- Department of Gastroenterology and Hepatology, University of Nebraska Medical Center, Omaha, NE
| | - Suresh Ponnada
- Department of Internal Medicine, Carilion Roanoke Memorial Hospital, Roanoke, VA
| | - 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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Xiao JB, Weng JY, Hu YY, Deng GL, Wan XJ. Feasibility and efficacy evaluation of metallic biliary stents eluting gemcitabine and cisplatin for extrahepatic cholangiocarcinoma. World J Gastroenterol 2020; 26:4589-4606. [PMID: 32884219 PMCID: PMC7445865 DOI: 10.3748/wjg.v26.i31.4589] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Revised: 06/30/2020] [Accepted: 07/30/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Effective endoscopic management is fundamental for the treatment of extrahepatic cholangiocarcinoma (ECC). However, current biliary stents that are widely used in clinical practice showed no antitumor effect. Drug-eluting stents (DESs) may achieve a combination of local chemotherapy and biliary drainage to prolong stent patency and improve prognosis.
AIM To develop novel DESs coated with gemcitabine (GEM) and cisplatin (CIS)-coloaded nanofilms that can maintain the continuous and long-term release of antitumor agents in the bile duct to inhibit tumor growth and reduce systemic toxicity.
METHODS Stents coated with different drug-eluting components were prepared by the mixed electrospinning method, with poly-L-lactide-caprolactone (PLCL) as the drug-loaded nanofiber membrane and GEM and/or CIS as the antitumor agents. Four different DESs were manufactured with four drug-loading ratios (5%, 10%, 15%, and 20%), including bare-loaded (PLCL-0), single-drug-loaded (PLCL-GEM and PLCL-CIS), and dual-drug-loaded (PLCL-GC) stents. The drug release property, antitumor activity, and biocompatibility were evaluated in vitro and in vivo to confirm the feasibility and efficacy of this novel DES for ECC.
RESULTS The in vitro drug release study showed the stable, continuous release of both GEM and CIS, which was sustained for over 30 d without an obvious initial burst, and a higher drug-loaded content induced a lower release rate. The drug-loading ratio of 10% was used for further experiments due to its ideal inhibitory efficiency and relatively low toxicity. All drug-loaded nanofilms effectively inhibited the growth of EGI-1 cells in vitro and the tumor xenografts of nude mice in vivo; in addition, the dual-loaded nanofilm (PLCL-GC) had a significantly better effect than the single-drug-loaded nanofilms (P < 0.05). No significant differences in the serological analysis (P > 0.05) or histopathological changes were observed between the single-loaded and drug-loaded nanofilms after stent placement in the normal porcine biliary tract.
CONCLUSION This novel PLCL-GEM and CIS-eluting stent maintains continuous, stable drug release locally and inhibits tumor growth effectively in vitro and in vivo. It can also be used safely in normal porcine bile ducts. We anticipate that it might be considered an alternative strategy for the palliative therapy of ECC patients.
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Affiliation(s)
- Jing-Bo Xiao
- Department of Gastroenterology and Shanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 201620, China
- Hospitalist and Internal Medicine Inpatient Department, Shanghai Jiahui International Hospital, Shanghai 200233, China
| | - Jun-Yong Weng
- Department of General Surgery, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 201620, China
| | - Yang-Yang Hu
- Department of Gastroenterology and Shanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 201620, China
| | - Gui-Long Deng
- Department of General Surgery, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 201620, China
| | - Xin-Jian Wan
- Department of Gastroenterology and Shanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 201620, China
- Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China
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Influence of Polymer Composition on the Controlled Release of Docetaxel: A Comparison of Non-Degradable Polymer Films for Oesophageal Drug-Eluting Stents. Pharmaceutics 2020; 12:pharmaceutics12050444. [PMID: 32403329 PMCID: PMC7284596 DOI: 10.3390/pharmaceutics12050444] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Revised: 05/08/2020] [Accepted: 05/08/2020] [Indexed: 12/13/2022] Open
Abstract
Following the huge clinical success of drug-eluting vascular stents, there is a significant interest in the development of drug-eluting stents for other applications, such as the treatment of gastrointestinal (GI) cancers. Central to this process is understanding how particular drugs are released from stent coatings, which to a large extent is controlled by drug-polymer interactions. Therefore, in this study we investigated the release of docetaxel (DTX) from a selection of non-degradable polymer films. DTX-polymer films were prepared at various loadings (1, 5 and 10% w/w) using three commercially available polymers including poly(dimethylsiloxane) (PSi), poly (ethylene-co-vinyl acetate) (PEVA) and Chronosil polyurethane (PU). The formulations were characterised using different techniques such as photoacoustic Fourier-transform infrared (PA-FTIR) spectrophotometry, X-ray diffraction (XRD) and differential scanning calorimetry (DSC). The effect of DTX on the mechanical properties of the films, in-vitro release, and degradation tests were also assessed. For all polymers and DTX loadings, the drug was found to disperse homogenously without crystallisation within the polymer matrix. While no specific interactions were observed between DTX and PSi or PEVA, hydrogen-bonding appeared to be present between DTX and PU, which resulted in a concentration-dependent decrease in the Young’s moduli of the films due to disruption of inter-polymeric molecular interactions. In addition, the DTX-PU interactions were found to modulate drug release, providing near-linear release over 30 days, which was accompanied by a significant reduction in degradation products. The results indicate that DTX-loaded PU films are excellent candidates for drug-eluting stents for the treatment of oesophageal cancer.
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Jang SI, Fang S, Baek YY, Lee DH, Na K, Lee SY, Lee DK. Local Delivery of Gemcitabine Inhibits Pancreatic and Cholangiocarcinoma Tumor Growth by Promoting Epidermal Growth Factor Receptor Degradation. Int J Mol Sci 2020; 21:ijms21051605. [PMID: 32111094 PMCID: PMC7084314 DOI: 10.3390/ijms21051605] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2019] [Revised: 02/22/2020] [Accepted: 02/24/2020] [Indexed: 12/14/2022] Open
Abstract
Gemcitabine is clinically used to treat certain types of cancers, including pancreatic and biliary cancer. We investigated the signal transduction pathways underlying the local antitumor effects of gemcitabine-eluting membranes (GEMs) implanted in pancreatic/biliary tumor-bearing nude mice. Here, we report that GEMs increased the E3 ubiquitin ligase c-CBL protein level, leading to degradation of epidermal growth factor receptor (EGFR) in SCK and PANC-1 cells. GEMs decreased the RAS and PI3K protein levels, leading to a reduction in the protein levels of active forms of downstream signaling molecules, including PDK, AKT, and GSK3β. GEM reduced proliferation of cancer cells by upregulating cell cycle arrest proteins, particularly p53 and p21, and downregulating cyclin D1 and cyclin B. Moreover, GEMs reduced the levels of proangiogenic factors, including VEGF, VEGFR2, CD31, and HIF-1α, and inhibited tumor cell migration and invasion by inducing the expression of E-cadherin and reducing that of N-cadherin, snail, and vimentin. We demonstrated that local delivery of gemcitabine using GEM implants inhibited tumor cell growth by promoting c-CBL-mediated degradation of EGFR and inhibiting the proliferation, angiogenesis, and epithelial–mesenchymal transition of pancreatic/biliary tumors. Use of gemcitabine-eluting stents can improve stent patency by inhibiting the ingrowth of malignant biliary obstructions.
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Affiliation(s)
- Sung Ill Jang
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Korea; (S.I.J.); (Y.-Y.B.); (S.Y.L.)
| | - Sungsoon Fang
- Severance Biomedical Science Institute, BK21 Plus Project for Medical Science, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Korea;
| | - Yi-Yong Baek
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Korea; (S.I.J.); (Y.-Y.B.); (S.Y.L.)
| | - Don Haeng Lee
- Department of Internal Medicine, Inha University Hospital, Inha University College of Medicine, Incheon 22212, Korea;
- Utah-Inha DDS & Advanced Therapeutics Research Center, Incheon 22212, Korea
| | - Kun Na
- Department of Biotechnology, The Catholic University of Korea, Bucheon-si 14662, Korea;
| | - Su Yeon Lee
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Korea; (S.I.J.); (Y.-Y.B.); (S.Y.L.)
| | - Dong Ki Lee
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Korea; (S.I.J.); (Y.-Y.B.); (S.Y.L.)
- Correspondence: ; Tel.: +82-2-2019-3214; Fax: +82-2-3463-3882
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Jang SI, Jeong S, Lee DH, Na K, Yang S, Lee DK. Safety Evaluation of Paclitaxel-Eluting Biliary Metal Stent with Sodium Caprate in Porcine Biliary Tract. Gut Liver 2020; 13:471-478. [PMID: 30970427 PMCID: PMC6622565 DOI: 10.5009/gnl18454] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2018] [Revised: 11/16/2018] [Accepted: 11/18/2018] [Indexed: 12/13/2022] Open
Abstract
Background/Aims Metallic stents designed to relieve malignant biliary obstruction are susceptible to occlusive tumor ingrowth or overgrowth. In a previous report, we described metallic stents covered with paclitaxel-incorporated membrane (MSCPM-I, II) to prevent occlusion from tumor ingrowth via antitumor effect. This new generation paclitaxeleluting biliary stent is further endowed with sodium caprate (MSCPM-III) for enhanced drug delivery. The purpose of this study is to examine the safety of its drug delivery system in the porcine biliary tract. Methods MSCPM-III (10% [wt/vol] paclitaxel) and covered metal stents (CMSs) were endoscopically inserted in porcine bile ducts in vivo. Histologic biliary changes, levels of paclitaxel released, and various serum analytes (albumin, alkaline phosphate, aspartate transaminase, alanine transaminase, total protein, total bilirubin, and direct bilirubin) were assessed. Results Based on the intensity of reactive inflammation and fibrosis, changes in porcine biliary epithelium secondary to implanted MSCPM-III were deemed acceptable (i.e., safe). Histologic features in the MSCPM-III and CMS groups did not differ significantly. In a related serum analysis, paclitaxel release from MSCPM-III stents was below the limit of detection for 28 days. Biochemical analyses were also similar for the two groups, and no evidence of hepatic or renal toxicity was found in animals receiving MSCPM-III stents. Conclusions In a prototypic porcine trial, this newly devised metal biliary stent incorporating both paclitaxel and sodium caprate appears to be safe in the porcine bile duct.
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Affiliation(s)
- Sung Ill Jang
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Seok Jeong
- Department of Internal Medicine, Inha University Hospital, Inha University College of Medicine, Seoul, Korea.,Utah-Inha DDS & Advanced Therapeutics Research Center, Incheon, Korea
| | - Don Haeng Lee
- Department of Internal Medicine, Inha University Hospital, Inha University College of Medicine, Seoul, Korea.,Utah-Inha DDS & Advanced Therapeutics Research Center, Incheon, Korea
| | - Kun Na
- Department of Biotechnology, The Catholic University of Korea, Bucheon, Korea
| | - Sugeun Yang
- World Class Smart Lab, Department of New Drug Development, Inha University College of Medicine, Incheon, Korea
| | - Dong Ki Lee
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
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12
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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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13
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Arafat M, Fouladian P, Blencowe A, Albrecht H, Song Y, Garg S. Drug-eluting non-vascular stents for localised drug targeting in obstructive gastrointestinal cancers. J Control Release 2019; 308:209-231. [DOI: 10.1016/j.jconrel.2019.07.001] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2019] [Revised: 07/02/2019] [Accepted: 07/03/2019] [Indexed: 02/08/2023]
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14
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Nabi Z, Reddy DN. Endoscopic Palliation for Biliary and Pancreatic Malignancies: Recent Advances. Clin Endosc 2019; 52:226-234. [PMID: 30665289 PMCID: PMC6547342 DOI: 10.5946/ce.2019.003] [Citation(s) in RCA: 14] [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: 11/22/2018] [Revised: 12/17/2018] [Accepted: 12/17/2018] [Indexed: 02/06/2023] Open
Abstract
Malignancies of the pancreatobiliary system are usually unresectable at the time of diagnosis. As a consequence, a majority of these cases are candidates for palliative care. With advances in chemotherapeutic agents and multidisciplinary care, the survival rate in pancreatobiliary malignancies has improved. Therefore, there is a need to provide an effective and long-lasting palliative care for these patients. Endoscopic palliation is preferred to surgery as the former is associated with equal efficacy and reduced morbidity. The main role of endoscopic palliation in the vast majority of pancreatobiliary malignancies includes biliary and enteral stenting for malignant obstructive jaundice and gastric outlet obstruction, respectively. Recent advances in endoscopic palliation appear promising in imparting long-lasting relief of symptoms. Use of radiofrequency ablation and photodynamic therapy in malignant biliary obstruction has been shown to improve the survival rates as well as the patency of biliary stents. The emergence of endoscopic ultrasound (EUS) as a therapeutic tool has enhanced the capability of minimally invasive palliation in pancreatobiliary cancers. EUS is a valuable alternative to endoscopic retrograde cholangiopancreatography for the palliation of obstructive jaundice. More recently, EUS is emerging as an effective primary modality for biliary and gastric bypass.
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Affiliation(s)
- Zaheer Nabi
- Asian Institute of Gastroenterology, Hyderabad, India
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15
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Salerno R, Mezzina N, Ardizzone S. Endoscopic retrograde cholangiopancreatography, lights and shadows: Handle with care. World J Gastrointest Endosc 2019; 11:219-230. [PMID: 30918587 PMCID: PMC6425281 DOI: 10.4253/wjge.v11.i3.219] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2019] [Revised: 02/21/2019] [Accepted: 03/11/2019] [Indexed: 02/06/2023] Open
Abstract
The role of endoscopic retrograde cholangiopancreatography (ERCP) has dramatically changed in the last years, mainly into that of a therapeutic procedure. The treatment of benign biliary disease, like “difficult” choledocolithiasis, with endoscopic papillary large balloon dilation combined with endoscopic sphinterotomy has proven an effective and safe technique. Moreover, safety in ERCP has improved as well, with the prevention of post-ERCP pancreatitis and patient-to-patient transmission of infections. The advent of self-expandable metal stenting has radically changed the management of biliopancreatic malignant strictures, while the role for therapy of benign strictures is still controversial. In addition, cholangioscopy (though the direct visualization of the biliopancreatic ductal system) has allowed for characterization of indeterminate biliary strictures and facilitated rescue therapy of large biliary stones deemed removable. Encouraging data from tissue ablation techniques, such as photodynamic therapy and radiofrequency ablation, need to be confirmed by large sample size clinical controlled trials. On the other hand, we have no drug-coated stents yet available to implant and evidence for the use of biodegradable stents is still weak. The competency and privileging of ERCP and endoscopic ultrasonography have been analyzed longer but the switch between the two procedures, at the same time, is becoming ordinary; as such, the endoscopist interested in this field should undergo parallel edification through training plans. Finally, the American Society for Gastrointestinal Endoscopy’s statement on non-anesthesiologist administration of propofol for gastrointestinal endoscopy is not actually endorsed by the European Society of Anaesthesiology, having many medical-legal implications in some European countries.
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Affiliation(s)
- Raffaele Salerno
- Gastroenterology and Digestive Endoscopy Unit, ASST Fatebenefratelli Sacco, Milan 20121, Italy
| | - Nicolò Mezzina
- Gastrointestinal Unit, ASST Fatebenefratelli Sacco-Department of Biochemical and Clinical Sciences "L. Sacco", University of Milan, Milano 20100, Italy
| | - Sandro Ardizzone
- Gastrointestinal Unit, ASST Fatebenefratelli Sacco - Department of Biochemical and Clinical Sciences "L. Sacco", University of Milan, Milano 20100, Italy
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16
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Jang HH, Park SB, Hong JS, Lee HL, Song YH, Kim J, Jung YH, Kim C, Kim DM, Lee SE, Jeong YI, Kang DH. Piperlongumine-Eluting Gastrointestinal Stent Using Reactive Oxygen Species-Sensitive Nanofiber Mats for Inhibition of Cholangiocarcinoma Cells. NANOSCALE RESEARCH LETTERS 2019; 14:58. [PMID: 30778693 PMCID: PMC6379506 DOI: 10.1186/s11671-019-2887-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/26/2018] [Accepted: 01/31/2019] [Indexed: 05/03/2023]
Abstract
BACKGROUND The aim of this study is to fabricate drug-eluting gastrointestinal (GI) stent using reactive oxygen species (ROS)-sensitive nanofiber mats for treatment of cholangiocarcinoma (CCA) cell. A ROS-producing agent, piperlongumine (PL)-incorporated nanofiber mats were investigated for drug-eluting stent (DES) application. METHODS Selenocystamine-conjugated methoxy poly(ethylene glycol) (MePEG) was conjugated with poly(L-lactide) (PLA) to produce block copolymer (LEse block copolymer). Various ratios of poly(ε-caprolactone) (PCL) and LEse block copolymer were dissolved in organic solvent with PL, and then nanofiber mats were fabricated by electro-spinning techniques. RESULTS The higher amount of LEse in the blend of PCL/LEse resulted in the formation of granules while PCL alone showed fine nanofiber structure. Nanofiber mats composed of PCL/LEse polymer blend showed ROS-sensitive drug release, i.e., PL release rate from nanofiber mats was accelerated in the presence of hydrogen peroxide (H2O2) while nanofiber mats of PCL alone have small changes in drug release rate, indicating that PL-incorporated nanofiber membranes have ROS responsiveness. PL itself and PL released from nanofiber mats showed almost similar anticancer activity against various CCA cells. Furthermore, PL released from nanofiber mats properly produced ROS generation and induced apoptosis of CCA cells as well as PL itself. In HuCC-T1 cell-bearing mice, PL-incorporated nanofiber mats showed improvement in anticancer activity. CONCLUSION PL-incorporated ROS-sensitive nanofiber mats were coated onto GI stent and showed improved anticancer activity with ROS responsiveness. We suggested PL-incorporated ROS-sensitive nanofiber mats as a promising candidate for local treatment of CCA cells.
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Affiliation(s)
- Hyung Ha Jang
- School of Medicine, Pusan National University, Yangsan, Gyeongnam 50612 South Korea
| | - Su Bum Park
- Research Institute of Convergence of Biomedical Sciences, Pusan National University Yangsan Hospital, Yangsan, Gyeongnam 50612 South Korea
| | - Jeong Sup Hong
- Division of Animal Care, Yonam College, Cheonan, Chungnam 31005 South Korea
| | - Hye Lim Lee
- Research Institute of Convergence of Biomedical Sciences, Pusan National University Yangsan Hospital, Yangsan, Gyeongnam 50612 South Korea
| | - Yeon Hui Song
- Research Institute of Convergence of Biomedical Sciences, Pusan National University Yangsan Hospital, Yangsan, Gyeongnam 50612 South Korea
| | - Jungsoo Kim
- Research Institute of Convergence of Biomedical Sciences, Pusan National University Yangsan Hospital, Yangsan, Gyeongnam 50612 South Korea
| | - Yun Hye Jung
- Research Institute of Convergence of Biomedical Sciences, Pusan National University Yangsan Hospital, Yangsan, Gyeongnam 50612 South Korea
| | - Chan Kim
- Amotech Co. Ltd, Incheon, Gyeonggi-do South Korea
| | - Doo-Man Kim
- Department of Photonics Engineering, Chonnam National University, Gwangju, 61186 South Korea
| | - Sang Eun Lee
- Research Institute of Convergence of Biomedical Sciences, Pusan National University Yangsan Hospital, Yangsan, Gyeongnam 50612 South Korea
| | - Young-Il Jeong
- Research Institute of Convergence of Biomedical Sciences, Pusan National University Yangsan Hospital, Yangsan, Gyeongnam 50612 South Korea
| | - Dae Hwan Kang
- School of Medicine, Pusan National University, Yangsan, Gyeongnam 50612 South Korea
- Research Institute of Convergence of Biomedical Sciences, Pusan National University Yangsan Hospital, Yangsan, Gyeongnam 50612 South Korea
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17
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Efficacy and safety evaluation of paclitaxel-loaded metal stents in patients with malignant biliary obstructions. Eur J Surg Oncol 2018; 45:816-819. [PMID: 30389299 DOI: 10.1016/j.ejso.2018.10.533] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2018] [Revised: 10/19/2018] [Accepted: 10/22/2018] [Indexed: 01/14/2023] Open
Abstract
Paclitaxel-eluting covered metal stents (PECMSs) and metallic stents covered with a paclitaxel-incorporated membrane (MSCPMs) have been developed to increase stent patency by preventing tumor ingrowth. However, few studies have compared their efficacy and safety compared with conventional covered metal stents (CMSs). This study aimed to compare differences in efficacy and safety between PECMS/MSCPM and CMS by meta-analysis. A search of PubMed and Embase was conducted for randomized controlled trials of PECMS/MSCPM and CMS in patients with malignant biliary obstructions published between January 1966 and August 2017. A meta-analysis was performed to compare clinical outcomes and complications between stent types. A total of 221 patients from three studies were included. There were no significant differences between PECMS/MSCPM and CMS in stent patency duration (P = 0.128) or survival time (P = 0.363). Risk did not differ between PECMS/MSCPM and CMS for stent malfunction (hazard ratio [HR]: 1.13, 95% confidence interval [CI]: 0.63-2.02, P = 0.677 for all stent malfunction; HR: 1.39, 95% CI: 0.68-2.85, P = 0.362 for stent occlusion caused by tumor ingrowth; HR: 0.80, 95% CI: 0.34-1.91, P = 0.617 for stent occlusion caused by distal stent migration or sludge impaction), or complications (HR: 1.54, 95% CI: 0.70-3.39, P = 0.280 for all complications; HR: 0.42, 95% CI: 0.14-1.30, P = 0.131 for pancreatitis). The exception was cholangitis-like symptoms, the risk for which was higher in PECMS/MSCPM compared with CMS (HR: 3.93, 95% CI: 1.08-14.29, P = 0.038). Although PECMS/MSCPM may be associated with higher risk of cholangitis-like symptoms, the overall results were similar between PECMS/MSCPM and CMS. Further studies are warranted in larger populations of patients.
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18
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Jang SI, Lee SJ, Jeong S, Lee DH, Kim MH, Yoon HJ, Lee DK. Efficacy of a Multiplex Paclitaxel Emission Stent Using a Pluronic ® Mixture Membrane versus a Covered Metal Stent in Malignant Biliary Obstruction: A Prospective Randomized Comparative Study. Gut Liver 2018; 11:567-573. [PMID: 28335102 PMCID: PMC5491093 DOI: 10.5009/gnl16428] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2016] [Revised: 10/19/2016] [Accepted: 10/26/2016] [Indexed: 12/31/2022] Open
Abstract
Background/Aims A drug-eluting stent for unresectable malignant biliary obstruction was developed to increase stent patency by preventing tumor ingrowth. The safety and efficacy of a new generation of metallic stents covered with a paclitaxel-incorporated membrane using a Pluronic® mixture (MSCPM-II) were compared prospectively with those of covered metal stents (CMSs) in patients with malignant biliary obstructions. Methods This study was initially designed as a prospective randomized trial but was closed early because of a high incidence of early occlusion. Therefore, the data were analyzed using the intent-to-treat method. A total of 72 patients with unresectable distal malignant biliary obstructions were prospectively enrolled. Results The two groups did not differ significantly in basic characteristics and mean follow-up period (MSCPM-II 194 days vs CMS 277 days, p=0.063). Stent occlusion occurred in 14 patients (35%) who received MSCPM-II and in seven patients (21.9%) who received CMSs. Stent patency and survival time did not significantly differ between the two groups (p=0.355 and p=0.570). The complications were mild and resolved by conservative management in both groups. Conclusions There were no significant differences in stent patency or patient survival in MSCPM-II and CMS patients with malignant biliary obstructions.
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Affiliation(s)
- Sung Ill Jang
- Department of Internal Medicine, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea.,Department of Medicine, The Graduate School of Yonsei University, Yonsei University College of Medicine, Seoul, Korea
| | - Se Joon Lee
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Seok Jeong
- Department of Internal Medicine, Inha University Hospital, Inha University College of Medicine, Incheon, Korea
| | - Don Haeng Lee
- Department of Internal Medicine, Inha University Hospital, Inha University College of Medicine, Incheon, Korea.,Utah-Inha Drug Delivery System & Advanced Therapeutics Research Center, Incheon, Korea
| | - Myung-Hwan Kim
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hong Jin Yoon
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Dong Ki Lee
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
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19
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Krishnagopal A, Reddy A, Sen D. Stent-mediated gene and drug delivery for cardiovascular disease and cancer: A brief insight. J Gene Med 2018; 19. [PMID: 28370939 DOI: 10.1002/jgm.2954] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2017] [Revised: 03/23/2017] [Accepted: 03/28/2017] [Indexed: 12/17/2022] Open
Abstract
This review concisely recapitulates the different existing modes of stent-mediated gene/drug delivery, their considerable advancement in clinical trials and a rationale for other merging new technologies such as nanotechnology and microRNA-based therapeutics, in addition to addressing the limitations in each of these perpetual stent platforms. Over the past decade, stent-mediated gene/drug delivery has materialized as a hopeful alternative for cardiovascular disease and cancer in contrast to routine conventional treatment modalities. Regardless of the phenomenal recent developments achieved by coronary interventions and cancer therapies that employ gene and drug-eluting stents, practical hurdles still remain a challenge. The present review highlights the limitations that each of the existing stent-based gene/drug delivery system encompasses and therefore provides a vision for the future with respect to discovering an ideal stent therapeutic platform that would circumvent all the practical hurdles witnessed with the existing technology. Further study of the improvisation of next-generation drug-eluting stents has helped to overcome the issue of restenosis to some extent. However, current stent formulations fall short of the anticipated clinically meaningful outcomes and there is an explicit need for more randomized trials aiming to further evaluate stent platforms in favour of enhanced safety and clinical value. Gene-eluting stents may hold promise in contributing new ideas for stent-based prevention of in-stent restenosis through genetic interventions by capitalizing on a wide variety of molecular targets. Therefore, the central consideration directs us toward finding an ideal stent therapeutic platform that would tackle all of the gaps in the existing technology.
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Affiliation(s)
| | - Aakash Reddy
- Cellular and Molecular Therapeutics Laboratory, Centre for Biomaterials, Cellular and Molecular Theranostics (CBCMT), VIT University, Vellore, Tamil Nadu, India
| | - Dwaipayan Sen
- Cellular and Molecular Therapeutics Laboratory, Centre for Biomaterials, Cellular and Molecular Theranostics (CBCMT), VIT University, Vellore, Tamil Nadu, India
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20
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Deipolyi AR, Covey AM. Palliative Percutaneous Biliary Interventions in Malignant High Bile Duct Obstruction. Semin Intervent Radiol 2017; 34:361-368. [PMID: 29249860 DOI: 10.1055/s-0037-1608827] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The optimal palliative intervention for malignant biliary obstruction is internal drainage by placement of a metallic stent. For patients with hilar biliary obstruction or low bile duct obstruction in whom endoscopy is not feasible, a percutaneous transhepatic approach in interventional radiology is preferred. This article reviews the rationale for this approach, periprocedural management, and techniques to optimize stent patency.
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Affiliation(s)
- Amy R Deipolyi
- Department of Radiology, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical Center, New York, New York
| | - Anne M Covey
- Department of Radiology, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical Center, New York, New York
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21
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Kwak TW, Lee HL, Song YH, Kim C, Kim J, Seo SJ, Jeong YI, Kang DH. Vorinostat-eluting poly(DL-lactide-co-glycolide) nanofiber-coated stent for inhibition of cholangiocarcinoma cells. Int J Nanomedicine 2017; 12:7669-7680. [PMID: 29089762 PMCID: PMC5655133 DOI: 10.2147/ijn.s141920] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Purpose The aim of this study was to fabricate a vorinostat (Zolinza™)-eluting nanofiber membrane-coated gastrointestinal (GI) stent and to study its antitumor activity against cholangiocarcinoma (CCA) cells in vitro and in vivo. Methods Vorinostat and poly(DL-lactide-co-glycolide) dissolved in an organic solvent was sprayed onto a GI stent to make a nanofiber-coated stent using an electro-spinning machine. Intact vorinostat and vorinostat released from nanofibers was used to assess anticancer activity in vitro against various CCA cells. The antitumor activity of the vorinostat-eluting nanofiber membrane-coated stent was evaluated using HuCC-T1 bearing mice. Results A vorinostat-incorporated polymer nanofiber membrane was formed on the surface of the GI stent. Vorinostat was continuously released from the nanofiber membrane over 10 days, and its release rate was higher in cell culture media than in phosphate-buffered saline. Released vorinostat showed similar anticancer activity against various CCA cells in vitro compared to that of vorinostat. Like vorinostat, vorinostat released from nanofibers induced acetylation of histone H4 and inhibited histone deacetylases 1⋅3⋅4/5/7 expression in vitro and in vivo. Furthermore, vorinostat nanofibers showed a higher tumor growth inhibition rate in HuCC-T1 bearing mice than vorinostat injections. Conclusion Vorinostat-eluting nanofiber membranes showed significant antitumor activity against CCA cells in vitro and in vivo. We suggest the vorinostat nanofiber-coated stent may be a promising candidate for CCA treatment.
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Affiliation(s)
- Tae Won Kwak
- Medical Convergence Textile Center, Gyeongbuk, Republic of Korea
| | - Hye Lim Lee
- Biomedical Research Institute, Pusan National University Hospital, Pusan, Republic of Korea
| | - Yeon Hui Song
- Biomedical Research Institute, Pusan National University Hospital, Pusan, Republic of Korea
| | - Chan Kim
- Amogreentech Co. Ltd. Gyeonggi-do, Republic of Korea
| | - Jungsoo Kim
- Biomedical Research Institute, Pusan National University Hospital, Pusan, Republic of Korea
| | - Sol-Ji Seo
- Biomedical Research Institute, Pusan National University Hospital, Pusan, Republic of Korea
| | - Young-Il Jeong
- Biomedical Research Institute, Pusan National University Hospital, Pusan, Republic of Korea
| | - Dae Hwan Kang
- Biomedical Research Institute, Pusan National University Hospital, Pusan, Republic of Korea.,Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Gyeongnam, Republic of Korea
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22
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Kim JY, Ko GB, Lee TH, Park SH, Lee YN, Cho YS, Jung Y, Chung IK, Choi HJ, Cha SW, Moon JH, Cho YD, Kim SJ. Partially Covered Metal Stents May Not Prolong Stent Patency Compared to Uncovered Stents in Unresectable Malignant Distal Biliary Obstruction. Gut Liver 2017; 11:440-446. [PMID: 28208003 PMCID: PMC5417788 DOI: 10.5009/gnl16245] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2016] [Revised: 07/31/2016] [Accepted: 09/20/2016] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND/AIMS Controversy still exists regarding the benefits of covered self-expandable metal stents (SEMSs) compared to uncovered SEMSs. We aimed to compare the patency and stent-related adverse events of partially covered SEMSs (PC-SEMSs) and uncovered SEMSs in unresectable malignant distal biliary obstruction. METHODS A total of 134 patients who received a PC-SEMS or uncovered SEMS for palliation of unresectable malignant distal biliary obstruction were reviewed retrospectively. The main outcome measures were stent patency, stent-related adverse events, and overall survival. RESULTS The median stent patency was 118 days (range, 3 to 802 days) with PC-SEMSs and 105 days (range, 2 to 485 days) with uncovered SEMSs (p=0.718). The overall endoscopic revision rate due to stent dysfunction was 36.6% (26/71) with PC-SEMSs and 36.5% (23/63) with uncovered SEMSs (p=0.589). Tumor ingrowth was more frequent with uncovered SEMSs (4.2% vs 19.1%, p=0.013), but migration was more frequent with PC-SEMSs (11.2% vs 1.5%, p=0.04). The incidence of stent-related adverse events was 2.8% (2/71) with PC-SEMSs and 9.5% (6/63) with uncovered SEMSs (p=0.224). The median overall survival was 166 days with PC-SEMSs and 168 days with uncovered SEMSs (p=0.189). CONCLUSIONS Compared to uncovered SEMSs, PC-SEMSs did not prolong stent patency in unresectable malignant distal biliary obstruction. Stent migration was more frequent with PC-SEMSs. However, tumor ingrowth was less frequent with PC-SEMSs compared to uncovered SEMSs.
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Affiliation(s)
- Jae Yun Kim
- Division of Gastroenterology, Department of Internal Medicine, Soonchunhyang University College of Medicine, Cheonan,
Korea
| | - Gyu Bong Ko
- Division of Gastroenterology, Department of Internal Medicine, Soonchunhyang University College of Medicine, Cheonan,
Korea
| | - Tae Hoon Lee
- Division of Gastroenterology, Department of Internal Medicine, Soonchunhyang University College of Medicine, Cheonan,
Korea
- Correspondence to: Tae Hoon Lee, Division of Gastroenterology, Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicine, 31 Suncheonhyang 6-gil, Dongnam-gu, Cheonan 31151, Korea, Tel: +82-41-570-3662, Fax: +82-41-574-5762, E-mail:
| | - Sang-Heum Park
- Division of Gastroenterology, Department of Internal Medicine, Soonchunhyang University College of Medicine, Cheonan,
Korea
| | - Yun Nah Lee
- Division of Gastroenterology, Department of Internal Medicine, Soonchunhyang University College of Medicine, Bucheon,
Korea
| | - Young Sin Cho
- Division of Gastroenterology, Department of Internal Medicine, Soonchunhyang University College of Medicine, Cheonan,
Korea
| | - Yunho Jung
- Division of Gastroenterology, Department of Internal Medicine, Soonchunhyang University College of Medicine, Cheonan,
Korea
| | - Il-Kwun Chung
- Division of Gastroenterology, Department of Internal Medicine, Soonchunhyang University College of Medicine, Cheonan,
Korea
| | - Hyun Jong Choi
- Division of Gastroenterology, Department of Internal Medicine, Soonchunhyang University College of Medicine, Bucheon,
Korea
| | - Sang-Woo Cha
- Division of Gastroenterology, Department of Internal Medicine, Soonchunhyang University College of Medicine, Seoul,
Korea
| | - Jong Ho Moon
- Division of Gastroenterology, Department of Internal Medicine, Soonchunhyang University College of Medicine, Bucheon,
Korea
| | - Young Deok Cho
- Division of Gastroenterology, Department of Internal Medicine, Soonchunhyang University College of Medicine, Seoul,
Korea
| | - Sun-Joo Kim
- Division of Gastroenterology, Department of Internal Medicine, Soonchunhyang University College of Medicine, Cheonan,
Korea
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23
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Hai R, Kuban J. Percutaneous intervention for bilioenteric anastomotic strictures: Current strategies and future directions. GASTROINTESTINAL INTERVENTION 2017. [DOI: 10.18528/gii160034] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Affiliation(s)
- Rayhan Hai
- Department of Interventional Radiology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Joshua Kuban
- Department of Interventional Radiology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
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Palliation With Endoscopic Metal Stents May Be Preferable to Surgical Intervention for Patients With Obstructive Pancreatic Head Adenocarcinoma. Int Surg 2016; 100:1104-10. [PMID: 26414833 DOI: 10.9738/intsurg-d-14-00274.1] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
The aim of this study was to evaluate the efficacy of endoscopically placed metal stents in comparison with operative procedures, in patients with obstructive pancreatic head cancer. Endoscopic stenting techniques and materials for gastrointestinal malignancies are constantly improving. Despite this evolution, many still consider operative procedures to be the gold standard for palliation in patients with unresectable obstructive pancreatic head cancer. This is a retrospective study of 52 patients who were diagnosed with obstructive (biliary, duodenal, or both) adenocarcinoma of the pancreatic head. Twenty-nine patients (endoscopy group) underwent endoscopic stenting. Eleven patients (bypass group) underwent biliodigestive bypass. Twelve patients (Whipple group) underwent Whipple operation with curative intent; however, histopathology revealed R1 resection (palliative Whipple). T4 disease was identified in 13 (44.8%), 7 (63.6%), and 3 (25%) patients in the endoscopy, bypass, and Whipple groups, respectively. Metastatic disease was present only in the endoscopy group (n = 12; 41.3%). There was no intervention-related mortality. Median survival was 280 days [95% confidence interval (95% CI), 103, 456 days], 157 days (95% CI, 0, 411 days), and 647 days (95% CI, 300, 993 days) for the endoscopy, bypass, and Whipple groups, respectively (P = 0.111). In patients with obstructive pancreatic head cancer, endoscopic stenting may offer equally good palliation compared with surgical double bypass. The numerically (not statistically) better survival after palliative Whipple might be explained by the smaller tumor burden in this subgroup of patients and not by the superior efficacy of this operation.
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25
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Boulay BR, Birg A. Malignant biliary obstruction: From palliation to treatment. World J Gastrointest Oncol 2016; 8:498-508. [PMID: 27326319 PMCID: PMC4909451 DOI: 10.4251/wjgo.v8.i6.498] [Citation(s) in RCA: 61] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2015] [Revised: 11/04/2015] [Accepted: 04/22/2016] [Indexed: 02/05/2023] Open
Abstract
Malignant obstruction of the bile duct from cholangiocarcinoma, pancreatic adenocarcinoma, or other tumors is a common problem which may cause debilitating symptoms and increase the risk of subsequent surgery. The optimal treatment - including the decision whether to treat prior to resection - depends on the type of malignancy, as well as the stage of disease. Preoperative biliary drainage is generally discouraged due to the risk of infectious complications, though some situations may benefit. Patients who require neoadjuvant therapy will require decompression for the prolonged period until attempted surgical cure. For pancreatic cancer patients, self-expanding metallic stents are superior to plastic stents for achieving lasting decompression without stent occlusion. For cholangiocarcinoma patients, treatment with percutaneous methods or nasobiliary drainage may be superior to endoscopic stent placement, with less risk of infectious complications or failure. For patients of either malignancy who have advanced disease with palliative goals only, the choice of stent for endoscopic decompression depends on estimated survival, with plastic stents favored for survival of < 4 mo. New endoscopic techniques may actually extend stent patency and patient survival for these patients by achieving local control of the obstructing tumor. Both photodynamic therapy and radiofrequency ablation may play a role in extending survival of patients with malignant biliary obstruction.
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26
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Indolfi L, Ligorio M, Ting DT, Xega K, Tzafriri AR, Bersani F, Aceto N, Thapar V, Fuchs BC, Deshpande V, Baker AB, Ferrone CR, Haber DA, Langer R, Clark JW, Edelman ER. A tunable delivery platform to provide local chemotherapy for pancreatic ductal adenocarcinoma. Biomaterials 2016; 93:71-82. [PMID: 27082874 DOI: 10.1016/j.biomaterials.2016.03.044] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2015] [Revised: 03/06/2016] [Accepted: 03/28/2016] [Indexed: 02/09/2023]
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the most devastating and painful cancers. It is often highly resistant to therapy owing to inherent chemoresistance and the desmoplastic response that creates a barrier of fibrous tissue preventing transport of chemotherapeutics into the tumor. The growth of the tumor in pancreatic cancer often leads to invasion of other organs and partial or complete biliary obstruction, inducing intense pain for patients and necessitating tumor resection or repeated stenting. Here, we have developed a delivery device to provide enhanced palliative therapy for pancreatic cancer patients by providing high concentrations of chemotherapeutic compounds locally at the tumor site. This treatment could reduce the need for repeated procedures in advanced PDAC patients to debulk the tumor mass or stent the obstructed bile duct. To facilitate clinical translation, we created the device out of currently approved materials and drugs. We engineered an implantable poly(lactic-co-glycolic)-based biodegradable device that is able to linearly release high doses of chemotherapeutic drugs for up to 60 days. We created five patient-derived PDAC cell lines and tested their sensitivity to approved chemotherapeutic compounds. These in vitro experiments showed that paclitaxel was the most effective single agent across all cell lines. We compared the efficacy of systemic and local paclitaxel therapy on the patient-derived cell lines in an orthotopic xenograft model in mice (PDX). In this model, we found up to a 12-fold increase in suppression of tumor growth by local therapy in comparison to systemic administration and reduce retention into off-target organs. Herein, we highlight the efficacy of a local therapeutic approach to overcome PDAC chemoresistance and reduce the need for repeated interventions and biliary obstruction by preventing local tumor growth. Our results underscore the urgent need for an implantable drug-eluting platform to deliver cytotoxic agents directly within the tumor mass as a novel therapeutic strategy for patients with pancreatic cancer.
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Affiliation(s)
- Laura Indolfi
- Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA; Departments of Surgery, Medicine, and Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
| | - Matteo Ligorio
- Departments of Surgery, Medicine, and Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Department of Health Sciences, University of Genoa, Genoa, Italy
| | - David T Ting
- Departments of Surgery, Medicine, and Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
| | - Kristina Xega
- Departments of Surgery, Medicine, and Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | | | - Francesca Bersani
- Departments of Surgery, Medicine, and Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Nicola Aceto
- Departments of Surgery, Medicine, and Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Vishal Thapar
- Departments of Surgery, Medicine, and Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Bryan C Fuchs
- Departments of Surgery, Medicine, and Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Vikram Deshpande
- Departments of Surgery, Medicine, and Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Aaron B Baker
- Department of Biomedical Engineering, University of Texas at Austin, Austin, TX, USA
| | - Cristina R Ferrone
- Departments of Surgery, Medicine, and Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Daniel A Haber
- Departments of Surgery, Medicine, and Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA
| | - Robert Langer
- Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA; The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA
| | - Jeffrey W Clark
- Departments of Surgery, Medicine, and Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Elazer R Edelman
- Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA; Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
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27
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Jeong S. Basic Knowledge about Metal Stent Development. Clin Endosc 2016; 49:108-12. [PMID: 27000423 PMCID: PMC4821512 DOI: 10.5946/ce.2016.029] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2016] [Revised: 02/03/2016] [Accepted: 02/03/2016] [Indexed: 12/29/2022] Open
Abstract
Biliary self-expandable metal stents (SEMS), a group of non-vascular stents, have been used in the palliative management of biliary obstruction around the world. However, there are still unmet needs in the clinical application of biliary SEMS. Comprehensive understanding of the SEMS is required to resolve the drawbacks and difficulties of metal stent development. The basic structure of SEMS, including the materials and knitting methods of metal wires, covering materials, and radiopaque markers, are discussed in this review. What we know about the physical and mechanical properties of the SEMS is very important. With an understanding of the basic knowledge of metal stents, hurdles such as stent occlusion, migration, and kinking can be overcome to develop more ideal SEMS.
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Affiliation(s)
- Seok Jeong
- Digestive Disease Center, Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, Korea
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Shatzel J, Kim J, Sampath K, Syed S, Saad J, Hussain ZH, Mody K, Pipas JM, Gordon S, Gardner T, Rothstein RI. Drug eluting biliary stents to decrease stent failure rates: A review of the literature. World J Gastrointest Endosc 2016; 8:77-85. [PMID: 26839648 PMCID: PMC4724033 DOI: 10.4253/wjge.v8.i2.77] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2015] [Revised: 08/11/2015] [Accepted: 10/28/2015] [Indexed: 02/05/2023] Open
Abstract
Biliary stenting is clinically effective in relieving both malignant and non-malignant obstructions. However, there are high failure rates associated with tumor ingrowth and epithelial overgrowth as well as internally from biofilm development and subsequent clogging. Within the last decade, the use of prophylactic drug eluting stents as a means to reduce stent failure has been investigated. In this review we provide an overview of the current research on drug eluting biliary stents. While there is limited human trial data regarding the clinical benefit of drug eluting biliary stents in preventing stent obstruction, recent research suggests promise regarding their safety and potential efficacy.
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Shaikh M, Choudhury NR, Knott R, Garg S. Engineering Stent Based Delivery System for Esophageal Cancer Using Docetaxel. Mol Pharm 2015; 12:2305-17. [PMID: 25936529 DOI: 10.1021/mp500851u] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Esophageal cancer patients are often diagnosed as "advanced" cases. These patients are subjected to palliative stenting using self-expanding metallic stents (SEMS) to maintain oral alimentation. Unfortunately, SEMS get reoccluded due to tumor growth, in and over the stent struts. To investigate potential solutions to this problem, docetaxel (DTX) delivery films were prepared using PurSil AL 20 (PUS), which can be used as a covering material for the SEMS. Drug-polymer miscibility and interactions were studied. Bilayer films were prepared by adhering the blank film to the DTX loaded film in order to maintain the unidirectional delivery to the esophagus. In vitro release and the local DTX delivery were studied using in vitro permeation experiments. It was found that DTX and PUS were physically and chemically compatible. The bilayer films exhibited sustained release (>30 days) and minimal DTX permeation through esophageal tissues in vitro. The rate-determining step for the DTX delivery was calculated. It was found that >0.9 fraction of rate control lies with the esophageal tissues, suggesting that DTX delivery can be sustained for longer periods compared to the in vitro release observed. Thus, the bilayer films can be developed as a localized sustained delivery system in combination with the stent.
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Affiliation(s)
- Mohsin Shaikh
- †Centre for Pharmaceutical Innovation and Development (CPID), School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia 5000, Australia
| | - Namita Roy Choudhury
- ‡Ian Wark Research Institute, University of South Australia, Mawson Lakes Campus, Mawson Lakes, South Australia 5095, Australia
| | - Robert Knott
- §ANSTO, Locked Bag 2001, Kirrawee, New South Wales 2232, Australia
| | - Sanjay Garg
- †Centre for Pharmaceutical Innovation and Development (CPID), School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia 5000, Australia
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30
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Abstract
Endoscopic stenting is increasingly being used in the management of gastrointestinal luminal obstruction, and has become the current treatment of choice for the palliation of blockage caused by malignant or benign growths. A variety of stents have been developed to enhance the efficacy of the procedure, and improvements are ongoing. In this article, we review the history of, and recent advances in, gastrointestinal stenting. We describe the rationale behind the design as well as the resulting outcome for each stent type.
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Affiliation(s)
- Jin-Seok Park
- Digestive Disease Center, Department of Internal Medicine, Inha University School of Medicine, Incheon, Korea
| | - Seok Jeong
- Digestive Disease Center, Department of Internal Medicine, Inha University School of Medicine, Incheon, Korea. ; National Center of Efficacy Evaluation for the Development of Health Products Targeting Digestive Disorders (NCEED), Incheon, Korea
| | - Don Haeng Lee
- Digestive Disease Center, Department of Internal Medicine, Inha University School of Medicine, Incheon, Korea. ; National Center of Efficacy Evaluation for the Development of Health Products Targeting Digestive Disorders (NCEED), Incheon, Korea. ; Utah-Inha DDS & Advanced Therapeutics Research Center, Incheon, Korea
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31
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Bertani H, Frazzoni M, Mangiafico S, Caruso A, Manno M, Mirante VG, Pigò F, Barbera C, Manta R, Conigliaro R. Cholangiocarcinoma and malignant bile duct obstruction: A review of last decades advances in therapeutic endoscopy. World J Gastrointest Endosc 2015; 7:582-592. [PMID: 26078827 PMCID: PMC4461933 DOI: 10.4253/wjge.v7.i6.582] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2014] [Revised: 01/20/2015] [Accepted: 03/18/2015] [Indexed: 02/05/2023] Open
Abstract
In the last decades many advances have been achieved in endoscopy, in the diagnosis and therapy of cholangiocarcinoma, however blood test, magnetic resonance imaging, computed tomography scan may fail to detect neoplastic disease at early stage, thus the diagnosis of cholangiocarcinoma is achieved usually at unresectable stage. In the last decades the role of endoscopy has moved from a diagnostic role to an invaluable therapeutic tool for patients affected by malignant bile duct obstruction. One of the major issues for cholangiocarcinoma is bile ducts occlusion, leading to jaundice, cholangitis and hepatic failure. Currently, endoscopy has a key role in the work up of cholangiocarcinoma, both in patients amenable to surgical intervention as well as in those unfit for surgery or not amenable to immediate surgical curative resection owing to locally advanced or advanced disease, with palliative intention. Endoscopy allows successful biliary drainage and stenting in more than 90% of patients with malignant bile duct obstruction, and allows rapid reduction of jaundice decreasing the risk of biliary sepsis. When biliary drainage and stenting cannot be achieved with endoscopy alone, endoscopic ultrasound-guided biliary drainage represents an effective alternative method affording successful biliary drainage in more than 80% of cases. The purpose of this review is to focus on the currently available endoscopic management options in patients with cholangiocarcinoma.
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32
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Stents with specialized functions: drug-eluting stents and stents with antireflux devices. GASTROINTESTINAL INTERVENTION 2015. [DOI: 10.1016/j.gii.2015.03.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
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33
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Park JS, Jeong S, Lee DH. Recent Advances in Gastrointestinal Stent Development. Clin Endosc 2015; 48:209-15. [PMID: 26064820 PMCID: PMC4461664 DOI: 10.5946/ce.2015.48.3.209] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2015] [Accepted: 05/06/2015] [Indexed: 12/17/2022] Open
Abstract
Endoscopic stenting is increasingly being used in the management of gastrointestinal luminal obstruction, and has become the current treatment of choice for the palliation of blockage caused by malignant or benign growths. A variety of stents have been developed to enhance the efficacy of the procedure, and improvements are ongoing. In this article, we review the history of, and recent advances in, gastrointestinal stenting. We describe the rationale behind the design as well as the resulting outcome for each stent type.
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Affiliation(s)
- Jin-Seok Park
- Digestive Disease Center, Department of Internal Medicine, Inha University School of Medicine, Incheon, Korea
| | - Seok Jeong
- Digestive Disease Center, Department of Internal Medicine, Inha University School of Medicine, Incheon, Korea. ; National Center of Efficacy Evaluation for the Development of Health Products Targeting Digestive Disorders (NCEED), Incheon, Korea
| | - Don Haeng Lee
- Digestive Disease Center, Department of Internal Medicine, Inha University School of Medicine, Incheon, Korea. ; National Center of Efficacy Evaluation for the Development of Health Products Targeting Digestive Disorders (NCEED), Incheon, Korea. ; Utah-Inha DDS & Advanced Therapeutics Research Center, Incheon, Korea
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Molecular mechanism of local drug delivery with Paclitaxel-eluting membranes in biliary and pancreatic cancer: new application for an old drug. Gastroenterol Res Pract 2015; 2015:568981. [PMID: 25983747 PMCID: PMC4423024 DOI: 10.1155/2015/568981] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2014] [Revised: 10/06/2014] [Accepted: 10/07/2014] [Indexed: 12/31/2022] Open
Abstract
Implantation of self-expanding metal stents (SEMS) is palliation for patients suffering from inoperable malignant obstructions associated with biliary and pancreatic cancers. Chemotherapeutic agent-eluting stents have been developed because SEMS are susceptible to occlusion by tumor in-growth. We reported recently that paclitaxel-eluting SEMS provide enhanced local drug delivery in an animal model. However, little is known about the molecular mechanisms by which paclitaxel-eluting stents attenuate tumor growth. We investigated the signal transduction pathways underlying the antiproliferative effects of a paclitaxel-eluting membrane (PEM) implanted in pancreatic/cholangiocarcinoma tumor bearing nude mice. Molecular and cellular alterations were analyzed in the PEM-implanted pancreatic/cholangiocarcinoma xenograft tumors by Western blot, immunoprecipitation, and immunofluorescence. The quantities of paclitaxel released into the tumor and plasma were determined by liquid chromatography-tandem mass spectroscopy. Paclitaxel from the PEM and its diffusion into the tumor inhibited angiogenesis, which involved suppression of mammalian target of rapamycin (mTOR) through regulation of hypoxia inducible factor (HIF-1) and increased apoptosis. Moreover, implantation of the PEM inhibited tumor-stromal interaction-related expression of proteins such as CD44, SPARC, matrix metalloproteinase-2, and vimentin. Local delivery of paclitaxel from a PEM inhibited growth of pancreatic/cholangiocarcinoma tumors in nude mice by suppressing angiogenesis via the mTOR and inducing apoptosis signal pathway.
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Blero D, Huberty V, Devière J. Novel biliary self-expanding metal stents: indications and applications. Expert Rev Gastroenterol Hepatol 2015; 9:359-67. [PMID: 25231201 DOI: 10.1586/17474124.2015.960395] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Endoscopic insertion of a self-expanding metal stent (SEMS) through a malignant common bile duct stricture is the first line of palliation for malignant jaundice. Patency of these stents remains a major concern. SEMS dysfunction can result from tumor ingrowth, overgrowth and/or clogging. Initial SEMS modifications involved covering the central part of the stent in order to reduce ingrowth and ultimately increase patency. Fully covered stents became available shortly after reports of their use in human patients. The potential removability and radial strength of SEMS have led to evaluation of their use in new indications including benign biliary strictures, post sphincterotomy bleeding and perforation. Other aspects of development include the addition of features such as anti-reflux valves, drug elution and spontaneous biodegradability. These aspects and their clinical implications are reviewed and discussed.
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Affiliation(s)
- Daniel Blero
- CHU Charleroi et Vésale, ISPPC, Université Libre de Bruxelles, 1 boulevard Zoé Drion, 6000 Charleroi, Belgium
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Boulay BR, Parepally M. Managing malignant biliary obstruction in pancreas cancer: choosing the appropriate strategy. World J Gastroenterol 2014; 20:9345-53. [PMID: 25071329 PMCID: PMC4110566 DOI: 10.3748/wjg.v20.i28.9345] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2013] [Revised: 01/30/2014] [Accepted: 03/12/2014] [Indexed: 02/06/2023] Open
Abstract
Most patients with pancreatic cancer develop malignant biliary obstruction. Treatment of obstruction is generally indicated to relieve symptoms and improve morbidity and mortality. First-line therapy consists of endoscopic biliary stent placement. Recent data comparing plastic stents to self-expanding metallic stents (SEMS) has shown improved patency with SEMS. The decision of whether to treat obstruction and the means for doing so depends on the clinical scenario. For patients with resectable disease, preoperative biliary decompression is only indicated when surgery will be delayed or complications of jaundice exist. For patients with locally advanced disease, self-expanding metal stents are superior to plastic stents for long-term patency. For patients with advanced disease, the choice of metallic or plastic stent depends on life expectancy. When endoscopic stent placement fails, percutaneous or surgical treatments are appropriate. Endoscopic therapy or surgical approach can be used to treat concomitant duodenal and biliary obstruction.
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Non-vascular drug eluting stents as localized controlled drug delivery platform: Preclinical and clinical experience. J Control Release 2013; 172:105-117. [DOI: 10.1016/j.jconrel.2013.08.010] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2013] [Revised: 08/03/2013] [Accepted: 08/05/2013] [Indexed: 01/10/2023]
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Kwon CI, Ko KH, Hahm KB, Kang DH. Functional self-expandable metal stents in biliary obstruction. Clin Endosc 2013; 46:515-21. [PMID: 24143314 PMCID: PMC3797937 DOI: 10.5946/ce.2013.46.5.515] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2013] [Revised: 06/28/2013] [Accepted: 06/29/2013] [Indexed: 12/20/2022] Open
Abstract
Biliary stents are widely used not only for palliative treatment of malignant biliary obstruction but also for benign biliary diseases. Each plastic stent or self-expandable metal stent (SEMS) has its own advantages, and a proper stent should be selected carefully for individual condition. To compensate and overcome several drawbacks of SEMS, functional self-expandable metal stent (FSEMS) has been developed with much progress so far. This article looks into the outcomes and defects of each stent type for benign biliary stricture and describes newly introduced FSEMSs according to their functional categories.
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Affiliation(s)
- Chang-Il Kwon
- Digestive Disease Center, CHA Bundang Medical Center, CHA University, Seongnam, Korea
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