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Hosseiniasl SM, Felgendreff P, Tharwat M, Amiot B, AbuRmilah A, Minshew AM, Bornschlegl AM, Jalan-Sakrikar N, Smart M, Dietz AB, Huebert RC, Nyberg SL. Biodegradable biliary stents coated with mesenchymal stromal cells in a porcine choledochojejunostomy model. Cytotherapy 2023; 25:483-489. [PMID: 36842850 PMCID: PMC10399303 DOI: 10.1016/j.jcyt.2023.01.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2022] [Revised: 01/25/2023] [Accepted: 01/27/2023] [Indexed: 02/27/2023]
Abstract
BACKGROUND AIMS Roux en y anastomosis is a preferred method of biliary reconstruction in liver transplantation that involves living donors or pediatric patients. However, biliary stricture is a frequent and serious complication, accounting for up to 40% of biliary complications in these patients. Previously, we demonstrated that extraluminal delivery of adipose-derived (AD) mesenchymal stromal cells (MSCs) decreased peri-biliary fibrosis and increased neo-angiogenesis in a porcine model of duct-to-duct biliary anastomosis. In this study, we used a porcine model of Roux en y anastomosis to evaluate the beneficial impact of a novel intraluminal MSC delivery system. METHODS Nine animals were divided into three groups: no stent (group 1), bare stent (group 2) and stent coated with AD-MSCs (group 3). All animals underwent cholecystectomy with roux en y choledochojejunostomy. Two animals per group were followed for 4 weeks and one animal per group was followed for 8 weeks. Cholangiograms and blood were sampled at baseline and the end of study. Biliary tissue was collected and examined by Masson trichrome staining and immunohistochemical staining for MSC markers (CD34 and CD44) and for neo-angiogenesis (CD31). RESULTS Two of three animals in group 1 developed an anastomotic site stricture. No strictures were observed in the animals of group 2 or group 3. CD34 and CD44 staining showed that AD-MSCs engrafted successfully at the anastomotic site by intraluminal delivery (group 3). Furthermore, biliary tissue from group 3 showed significantly less fibrosis and increased angiogenesis compared with the other groups. CONCLUSIONS Intraluminal delivery of AD-MSCs resulted in successful biliary engraftment of AD-MSCs as well as reduced peri-biliary fibrosis and increased neo-angiogenesis.
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Affiliation(s)
| | - Philipp Felgendreff
- Department of Surgery, Mayo Clinic, Rochester, Minnesota, USA; Department for General, Visceral and Vascular Surgery, University Hospital Jena, Jena, Germany
| | - Mohammad Tharwat
- General Surgery Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Bruce Amiot
- Department of Surgery, Mayo Clinic, Rochester, Minnesota, USA; William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, Minnesota, USA
| | - Anan AbuRmilah
- Department of Surgery, Mayo Clinic, Rochester, Minnesota, USA
| | - Anna M Minshew
- Department of Surgery, Mayo Clinic, Rochester, Minnesota, USA
| | - Alexander M Bornschlegl
- Department of Laboratory Medicine and Pathology, Mayo Clinic and Foundation, Rochester, Minnesota, USA
| | - Nidhi Jalan-Sakrikar
- Gastroenterology Research Unit, Mayo Clinic and Foundation, Rochester, Minnesota, USA
| | - Michele Smart
- Department of Laboratory Medicine and Pathology, Mayo Clinic and Foundation, Rochester, Minnesota, USA
| | - Allan B Dietz
- Department of Laboratory Medicine and Pathology, Mayo Clinic and Foundation, Rochester, Minnesota, USA
| | - Robert C Huebert
- William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, Minnesota, USA; Gastroenterology Research Unit, Mayo Clinic and Foundation, Rochester, Minnesota, USA; Division of Gastroenterology and Hepatology, Mayo Clinic and Foundation, Rochester, Minnesota, USA
| | - Scott L Nyberg
- Department of Surgery, Mayo Clinic, Rochester, Minnesota, USA; William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, Minnesota, USA.
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Long-Term Results of Endoscopic Metal Stenting for Biliary Anastomotic Stricture after Liver Transplantation. J Clin Med 2023; 12:jcm12041453. [PMID: 36835988 PMCID: PMC9961020 DOI: 10.3390/jcm12041453] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2022] [Revised: 02/01/2023] [Accepted: 02/09/2023] [Indexed: 02/15/2023] Open
Abstract
(1) Background: Anastomotic biliary stricture (ABS) is a well-known complication of liver transplantation which can lead to secondary biliary cirrhosis and graft dysfunction. The goal of this study was to evaluate the long-term outcomes of endoscopic metal stenting of ABS in the setting of deceased donor liver transplantation (DDLT). (2) Methods: Consecutive DDLT patients with endoscopic metal stenting for ABS between 2010 and 2015 were screened. Data on diagnosis, treatment and follow-up (until June 2022) were collected. The primary outcome was endoscopic treatment failure defined as the need for surgical refection. (3) Results: Among the 465 patients who underwent LT, 41 developed ABS. It was diagnosed after a mean period of 7.4 months (+/-10.6) following LT. Endoscopic treatment was technically successful in 95.1% of cases. The mean duration of endoscopic treatment was 12.8 months (+/-9.1) and 53.7% of patients completed a 1-year treatment. After a mean follow-up of 6.9 years (+/-2.3), endoscopic treatment failed in nine patients (22%) who required surgical refection. Conclusions: Endoscopic management with metal stenting of ABS after DDLT was technically successful in most cases, and half of the patients had at least one year of indwelling stent. Endoscopic treatment long-term failure rate occurred in one fifth of the patients.
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Percutaneous transhepatic treatment for biliary stricture after duct-to-duct biliary anastomosis in living donor liver transplantation: a 9-year single-center experience. Eur Radiol 2022; 32:2414-2425. [DOI: 10.1007/s00330-021-08373-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Revised: 09/09/2021] [Accepted: 09/30/2021] [Indexed: 02/07/2023]
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Rao HB, Koshy AK, Priya K, Nair P, Sudhindran S, Venu RP. Endoscopic management of high-grade biliary strictures complicating living donor liver transplantation using soehendra stent retrievers. Scand J Gastroenterol 2021; 56:1103-1108. [PMID: 34242116 DOI: 10.1080/00365521.2021.1944300] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND Biliary strictures following living donor liver transplantation (LDLT) are usually managed by endoscopic retrograde cholangiography (ERC) with stricture dilation and stent placement. While current endoscopic techniques are successful in most cases, high-grade biliary strictures (HGBS) pose a challenge using currently employed techniques which have a low rate of technical success. AIMS In this study, we have explored the safety and efficacy of Soehendra stent retrievers (SSR) for the dilation of HGBS complicating LDLT. METHODS This was a prospective cohort study where all patients with anastomotic biliary strictures following LDLT from January 2016 till February 2018 were included. Patients with HGBS defined as the exclusive passage of 0.018-inch guidewire, were included in Group 1. In these patients, 5 Fr Soehendra stent retrievers were used to dilate HGBS over guidewire, using torsional movements. Technical success, safety and clinical response was compared with patients who required Per-cutaneous transhepatic cholangiography (PTC) with rendezvous procedure due to a failed ERC, before the commencement of the study (Group 2). RESULTS Ten patients with HGBS were included into Group 1. Technical success defined as successful placement of a biliary stent across the stricture was achieved in all the patients in group 1. Favorable response to endotherapy was higher in group 1(8/10 patients (80%)) as compared to group 2(6/14 patients (42.8%)). There were no post procedure complications in patients of group 1, while 3 patients developed cholangitis in group 2. CONCLUSIONS HGBS can be successfully treated with SSR for stricture dilation. It is safe with no significant complications and requires fewer procedures.
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Affiliation(s)
- Harshavardhan B Rao
- Department of Gastroenterology, Amrita Institute of Medical Sciences, Kochi, India
| | - Anoop K Koshy
- Department of Gastroenterology, Amrita Institute of Medical Sciences, Kochi, India
| | - Krishna Priya
- Department of Gastroenterology, Amrita Institute of Medical Sciences, Kochi, India
| | - Priya Nair
- Department of Gastroenterology, Amrita Institute of Medical Sciences, Kochi, India
| | - S Sudhindran
- Department of Gastrointestinal Surgery, Amrita Institute of Medical Sciences, Kochi, India
| | - Rama P Venu
- Department of Gastroenterology, Amrita Institute of Medical Sciences, Kochi, India
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Tao H, Wang P, Sun B, Zhou X, Xie J. One-step Percutaneous Transhepatic Cholangioscopy Combined With High-frequency Needle-knife Electrotomy in Biliary Strictures After Liver Transplantation. Surg Laparosc Endosc Percutan Tech 2021; 31:787-793. [PMID: 33935263 DOI: 10.1097/sle.0000000000000946] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2020] [Accepted: 02/08/2021] [Indexed: 11/26/2022]
Abstract
BACKGROUND Endoscopic management is the mainstay for biliary strictures after liver transplantation. However, this method is often failed in cases associated with hepatolithiasis or refractory strictures. The aim of this study is to investigate whether 1-step percutaneous transhepatic biliary cholangiography (PTC) combined with high-frequency needle-knife electrotomy can be an alternative method in biliary strictures after liver transplantation that could not be treated by endoscopic management. METHODS Clinical data of 14 patients suffering from biliary strictures after liver transplantation from June 2014 to January 2018 were retrospectively analyzed. One-step PTC combined with high-frequency needle-knife electrotomy was used to resolve the strictures. RESULTS One-step PTC was successfully performed in all 14 patients. In 10 of 12 (83.3%) patients with hepatolithiasis, the stones were removed completely. Stricture resolution was detected in 13 of 14 (92.9%) patients at first postoperative choledochoscopy. Three mild adverse events occurred (cholangitis, 2 patients; delayed hemobilia, 1 patient), but were resolved with conservative treatment. The follow-up after supporting catheter removal was 15.7±4.5 months. Only 1 patient (8.3%) had stone recurrence and no stenosis occurred during supporting-catheter-free follow-up. CONCLUSIONS One-step PTC combined with high-frequency needle-knife electrotomy seems to be a useful for treating biliary strictures after liver transplantation.
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Affiliation(s)
- Haisu Tao
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan
| | - Ping Wang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Beiwang Sun
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Xinghua Zhou
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Jiafen Xie
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
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Mukund A, Choudhury A, Das S, Pamecha V, Sarin SK. Salvage PTBD in post living donor liver transplant patients with biliary complications-a single centre retrospective study. Br J Radiol 2020; 93:20191046. [PMID: 31971831 DOI: 10.1259/bjr.20191046] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
OBJECTIVE To study the outcome of salvage percutaneous transhepatic biliary drainage (PTBD) in complex and technically challenging post-liver transplant (LT) biliary complications and analyse the reason for failure of endoscopic retrograde cholangiopancreatography (ERCP). METHODS AND MATERIALS Hospital data were searched for all LT patients with biliary complications requiring salvage PTBD (upon failure of ERCP) from January 2010 to May 2017. Patients who underwent primary PTBD were excluded. Patients clinical and biochemical parameters were analysed for clinical, biochemical and imaging response, stent-free survival and the reason for ERCP failure. RESULTS Salvage PTBD was performed in 32 patients with post-LT biliary stricture/bile leak presenting with deranged liver function in 12 (37.5%), cholangitis in 12 (37.5%) and cholangitis with cholangitic abscess in remaining 8 (25%) patients. Of 32 patients, 20 (62.5%) already had plastic biliary stent placed by ERCP, while in remaining (n = 12, 37.5%) a wire could not be negotiated across stricture by ERCP. These patients were found to have long/tortuous stricture (n = 18, 56.3%) and multiple duct disconnection at anastomosis (n = 14, 43.7%). Immediate as well as sustained (persisting for a year or more) clinical and biochemical improvement was seen in 26 (81.3%) patients, while failure of resolution of sepsis and death occurred in remaining 6 (18.8%). CONCLUSION Salvage PTBD is an effective treatment in difficult-to-treat post-LT biliary strictures with deranged liver functions with or without cholangitis/cholangitic abscess. It can reduce graft loss with improved clinical outcome. Post-LT ductal anatomy at anastomosis is important to decide the appropriate approach (ERCP/PTBD). ADVANCES IN KNOWLEDGE (1). PTBD as a salvage procedure in difficult anatomy or upon failure of ERCP-based intervention is effective and a good alternative strategy. (2). Postoperative surgical anatomy (type & length of stricture, number of ductanastomosis, location and graft-recipient duct alignment) is the key factor indeciding the appropriate therapeutic procedure.
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Affiliation(s)
- Amar Mukund
- Department of Radiology, Institute of Liver and Biliary Sciences, D-1, Vasant Kunj, New Delhi, India
| | - Ashok Choudhury
- Department of Hepatology, Institute of Liver and Biliary Sciences, D-1, Vasant Kunj, New Delhi, India
| | - Swati Das
- Department of Radiology, Institute of Liver and Biliary Sciences, D-1, Vasant Kunj, New Delhi, India
| | - Viniyendra Pamecha
- Department of Hepatobiliary Pancreatic surgery and Liver Transplantation, Institute of Liver and Biliary Sciences, D-1, Vasant Kunj, New Delhi, India
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, D-1, Vasant Kunj, New Delhi, India
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Kim YM, Chung TR, Lee DK. High-Level Biliary Strictures After Living-Donor Liver Transplantation. ADVANCED ERCP FOR COMPLICATED AND REFRACTORY BILIARY AND PANCREATIC DISEASES 2020:1-16. [DOI: 10.1007/978-981-13-0608-2_1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Paradigm shift in the management of bile duct strictures complicating living donor liver transplantation. Indian J Gastroenterol 2019; 38:488-497. [PMID: 32065353 DOI: 10.1007/s12664-019-01000-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2019] [Accepted: 09/20/2019] [Indexed: 02/06/2023]
Abstract
AIM Validation of new metrics to identify functionally significant obstruction (FSO), to better define biliary strictures complicating living donor liver transplantation (LDLT). METHODS All LDLT recipients who presented with cholestasis were studied. Novel metrics for FSO are as follows: (1) magnetic resonance cholangiopancreatography (MRCP) ductal ratio (MDR): The ratio between hepatic duct and recipient duct diameter on the MRCP taken at presentation; (2) endoscopic retrograde cholangiography (ERC) ductal ratio (EDR): The ratio between hepatic duct and recipient duct diameter on the first ERC done for suspected biliary strictures; (3) delayed contrast drainage (DCD): > 50% contrast retained above the anastomotic site, in more than three consecutive fluoroscopic images taken at least 15 min after contrast instillation. Association between these metrics and endotherapy response was analyzed along with patient demographics, intraoperative variables (cold ischemia time, blood transfusions, biliary anastomosis) and perioperative complications (hepatic artery thrombosis [HAT], bile leak). Favorable response to endotherapy was defined as symptomatic relief with ≥ 80% reduction in total bilirubin/alkaline phosphatase. RESULTS A total of 83 LDLT recipients presented with altered liver function tests. Favorable response was seen in 18/39 patients (46.2%). On univariate analysis, HAT, multiple biliary anastomoses, graft-to-recipient weight ratio (GRWR), MDR, EDR and DCD were significant (p value ≤ 0.05). On multivariate analysis, only MDR ≥ 1.15 was an independent predictor of favorable response to endotherapy (OR 48 [95% CI 7.096-324.71]). CONCLUSION A paradigm shift in the approach to management of biliary strictures complicating LDLT is proposed whereby a multidimensional definition of FSO can help in reliable patient selection for endotherapy and improve patient outcome as a whole.
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Creation of a Robotically Assisted Terminal Jejunogastrostomy Is Safe and Effective in Regaining Antegrade Enteral Bile Duct Access After Live Donor Liver Transplant With Roux Limb. Transplant Direct 2019; 5:e476. [PMID: 31576372 PMCID: PMC6708632 DOI: 10.1097/txd.0000000000000922] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2019] [Revised: 06/17/2019] [Accepted: 06/26/2019] [Indexed: 11/26/2022] Open
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Rao HB, Prakash A, Sudhindran S, Venu RP. Biliary strictures complicating living donor liver transplantation: Problems, novel insights and solutions. World J Gastroenterol 2018; 24:2061-2072. [PMID: 29785075 PMCID: PMC5960812 DOI: 10.3748/wjg.v24.i19.2061] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2018] [Revised: 04/28/2018] [Accepted: 05/11/2018] [Indexed: 02/06/2023] Open
Abstract
Biliary stricture complicating living donor liver transplantation (LDLT) is a relatively common complication, occurring in most transplant centres across the world. Cases of biliary strictures are more common in LDLT than in deceased donor liver transplantation. Endoscopic management is the mainstay for biliary strictures complicating LDLT and includes endoscopic retrograde cholangiography, sphincterotomy and stent placement (with or without balloon dilatation). The efficacy and safety profiles as well as outcomes of endoscopic management of biliary strictures complicating LDLT is an area that needs to be viewed in isolation, owing to its unique set of problems and attending complications; as such, it merits a tailored approach, which is yet to be well established. The diagnostic criteria applied to these strictures are not uniform and are over-reliant on imaging studies showing an anastomotic narrowing. It has to be kept in mind that in the setting of LDLT, a subjective anastomotic narrowing is present in most cases due to a mismatch in ductal diameters. However, whether this narrowing results in a functionally significant narrowing is a question that needs further study. In addition, wide variation in the endotherapy protocols practised in most centres makes it difficult to interpret the results and hampers our understanding of this topic. The outcome definition for endotherapy is also heterogenous and needs to be standardised to allow for comparison of data in this regard and establish a clinical practice guideline. There have been multiple studies in this area in the last 2 years, with novel findings that have provided solutions to some of these issues. This review endeavours to incorporate these new findings into the wider understanding of endotherapy for biliary strictures complicating LDLT, with specific emphasis on diagnosis of strictures in the LDLT setting, endotherapy protocols and outcome definitions. An attempt is made to present the best management options currently available as well as directions for future research in the area.
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Affiliation(s)
- Harshavardhan B Rao
- Department of Gastroenterology, Amrita Institute of Medical Sciences, Amrita University, Kochi 682041, India
| | - Arjun Prakash
- Department of Gastroenterology, Amrita Institute of Medical Sciences, Amrita University, Kochi 682041, India
| | - Surendran Sudhindran
- Department of Transplant and Vascular Surgery, Amrita Institute of Medical Sciences, Amrita University, Kochi 682041, India
| | - Rama P Venu
- Department of Gastroenterology, Amrita Institute of Medical Sciences, Amrita University, Kochi 682041, India
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