Paclitaxel-eluting balloon dilation of biliary anastomotic stricture after liver transplantation

AIM:To investigate the safety and effectiveness of endoscopic therapy with a paclitaxel-eluting balloon(PEB) for biliary anastomotic stricture(AS) after liver transplantation(LT).METHODS:This prospective pilot study enrolled 13 consecutive eligible patients treated for symptomatic AS after LT at the University Hospital of Münster between January 2011 and March 2014.The patients were treated by endoscopic therapy with a PEB and followed up every 8 wk by endoscopic retrograde cholangiopancreatography(ERCP).In cases of re-stenosis,further balloon dilation with a PEB was performed.Follow-up was continued until 24 mo after the last intervention.RESULTS:Initial technical feasibility,defined as successful balloon dilation with a PEB during the initial ERCP procedure,was achieved in 100% of cases.Long-term clinical success(LTCS),defined as no need for further endoscopic intervention for at least 24 mo,was achieved in 12 of the 13 patients(92.3%).The mean number of endoscopic interventions required to achieve LTCS was only 1.7 ± 1.1.Treatment failure,defined as the need for definitive alternative treatment,occurred in only one patient,who developed recurrent stenosis with increasing bile duct dilatation that required stent placement.CONCLUSION:Endoscopic therapy with a PEB is very effective for the treatment of AS after LT,and seems to significantly shorten the overall duration of endoscopic treatment by reducing the number of interventions needed to achieve LTCS.

Endoscopic ultrasound guided radiofrequency ablation,for pancreatic cystic neoplasms and neuroendocrine tumors

AIM: To outline the feasibility, safety, adverse events and early results of endoscopic ultrasound(EUS)-radiofrequency ablation(RFA) in pancreatic neoplasms using a novel probe. METHODS: This is a multi-center, pilot safety feasibility study. The intervention described was radiofrequency ablation(RF) which was applied with an innovative monopolar RF probe(1.2 mm Habib EUS-RFA catheter) placed through a 19 or 22 gauge fine needle aspiration(FNA) needle once FNA was performed in patients with a tumor in the head of the pancreas. The HabibTM EUSRFA is a 1 Fr wire(0.33 mm, 0.013") with a working length of 190 cm, which can be inserted through the biopsy channel of an echoendoscope. RF power is applied to the electrode at the end of the wire to coagulate tissue in the liver and pancreas.RESULTS: Eight patients [median age of 65(range 27-82) years; 7 female and 1 male] were recruited in a prospective multicenter trial. Six had a pancreatic cysticneoplasm(four a mucinous cyst, one had intraductal papillary mucinous neoplasm and one a microcystic adenoma) and two had a neuroendocrine tumors(NET) in the head of pancreas. The mean size of the cystic neoplasm and NET were 36.5 mm(SD ± 17.9 mm) and 27.5 mm(SD ± 17.7 mm) respectively. The EUSRFA was successfully completed in all cases. Among the 6 patients with a cystic neoplasm, post procedure imaging in 3-6 mo showed complete resolution of the cysts in 2 cases, whilst in three more there was a 48.4% reduction [mean pre RF 38.8 mm(SD ± 21.7 mm) vs mean post RF 20 mm(SD ± 17.1 mm)] in size. In regards to the NET patients, there was a change in vascularity and central necrosis after EUS-RFA. No major complications were observed within 48 h of the procedure. Two patients had mild abdominal pain that resolved within 3 d. CONCLUSION: EUS-RFA of pancreatic neoplasms with a novel monopolar RF probe was well tolerated in all cases. Our preliminary data suggest that the procedure is straightforward and safe. The response ranged from complete resolution to a 50% reduction in size.

Lipids in liver transplant recipients

Hyperlipidemia is very common after liver transplantation and can be observed in up to 71% of patients. The etiology of lipid disorders in these patients is multifactorial, with different lipid profiles observed depending on the immunosuppressive agents administered and the presence of additional risk factors, such as obesity, diabetes mellitus and nutrition. Due to recent improvements in survival of liver transplant recipients, the prevention of cardiovascular events has become more important, especially as approximately 64% of liver transplant recipients present with an increased risk of cardiovascular events. Management of dyslipidemia and of other modifiable cardiovascular risk factors, such as hypertension, diabetes and smoking, has therefore become essential in these patients. Treatment of hyperlipidemia after liver transplantation consists of life style modification, modifying the dose or type of immunosuppressive agents and use of lipid lowering agents. At the start of administration of lipid lowering medications, it is important to monitor drugdrug interactions, especially between lipid lowering agents and immunosuppressive drugs. Furthermore, as combinations of various lipid lowering drugs can lead to severe side effects, such as myopathies and rhabdomyolysis, these combinations should therefore be avoided. To our knowledge, there are no current guidelines targeting the management of lipid metabolism disorders in liver transplant recipients. This paper therefore recommends an approach of managing lipid abnormalities occurring after liver transplantation.

Single-operator cholangioscopy for biliary complications in liver transplant recipients

AIM To evaluate cholangioscopy in addition to endoscopic retrograde cholangiopancreatography(ERCP) for management of biliary complications after liver transplantation(LT).METHODS Twenty-six LT recipients with duct-to-duct biliary reconstruction who underwent ERCP for suspected biliary complications between April and December2016 at the university hospital of Muenster were consecutively enrolled in this observational study. After evaluating bile ducts using fluoroscopy, cholangioscopy using a modern digital single-operator cholangioscopy s y s t e m(S py G la s s D S ?) wa s pe r fo r me d dur ing the same procedure with patients under conscious sedation. All patients received peri-interventional antibiotic prophylaxis and bile was collected during the intervention for microbial analysis and for antibiotic susceptibility testing.RESULTS Thirty-three biliary complications were found in a total of 22 patients, whereas four patients showed normal bile ducts. Anastomotic strictures were evident in 14(53.8%) patients, non-anastomotic strictures in seven(26.9%), biliary cast in three(11.5%), and stones in six(23.1%). A benefit of cholangioscopy was seen in 12(46.2%) patients. In four of them, cholangioscopy was crucial for selective guidewire placement prior to planned intervention. In six patients, biliary cast and/or stones failed to be diagnosed by ERCP and were only detectable through cholangioscopy. In one case, a bile duct ulcer due to fungal infection was diagnosed by cholangioscopy. In another case, signs of bile duct inflammation caused by acute cholangitis were evident. One patient developed post-interventional cholangitis. No further procedure-related complications occurred. Thirty-seven isolates were found in bile. Sixteen of these were gram-positive(43.2%), 12(32.4%) were gram-negative bacteria, and Candida species accounted for 24.3% of all isolated microorganisms. Interestingly, only 48.6% of specimens were sensitive to prophylactic antibiotics.CONCLUSION Single-operator cholangioscopy can provide important diagnostic information, helping endoscopists to plan and perform interventional procedures in LT-related biliary complications.

Role of anti-angiogenesis therapy in the management of hepatocellular carcinoma: The jury is still out

As the leading cause of disease-related deaths,cancer is a major public health threat worldwide.Surgical resection is still the first-line therapy for patients with early-stage cancers.However,postoperative relapse and metastasis remain the cause of 90%of deaths of patients with solid organ malignancies,including hepatocellular carcinoma(HCC).With the rapid development of molecular biology techniques in recent years,molecularly targeted therapies using monoclonal antibodies,small molecules,and vaccines have become a milestone in cancer therapeutic by significantly improv-ing the survival of cancer patients,and have opened a window of hope for patients with advanced cancer.Hypervascularization is a major characteristic of HCC.It has been reported that anti-angiogenic treatments,which inhibit blood vessel formation,are highly effective for treating HCC.However,the efficacy and safety of anti-angiogenesis therapies remain controversial.Sorafenib is an oral multikinase inhibitor with antiproliferative and anti-angiogenic effects and is the first molecular target drug approved for the treatment of advanced HCC.While sorafenib has shown promising therapeutic effects,substantial evidence of primary and acquired resistance to sorafenib has been reported.Numerous clinical trials have been conducted to evaluate a large number of molecularly targeted drugs for treating HCC,but most drugs exhibited less efficacy and/or higher toxicity compared to sorafenib.Therefore,understanding the mechanism(s)underlying sorafenib resistance of cancer cells is highlighted for efficiently treating HCC.This concise review aims to provide an overview of anti-angiogenesis therapy in the management of HCC and to discuss the common mechanisms of resistance to anti-angiogenesis therapies.

Risk of venous congestion in live donors of extended right liver graft

AIM: To investigate middle hepatic vein(MHV)management in adult living donor liver transplantation and safer remnant volumes(RV).METHODS: There were 59 grafts with and 12 grafts without MHV(including 4 with MHV-5/8 reconstructions).All donors underwent our five-step protocol evaluation containing a preoperative protocol liver biopsy Congestive vs non-congestive RV, remnantvolumebody-weight ratios(RVBWR) and postoperative outcomes were evaluated in 71 right graft living donors. Dominant vs non-dominant MHV anatomy in total liver volume(d-MHV/TLV vs nd-MHV/TLV) was constellated with large/small congestion volumes(CVindex).Small for size(SFS) and non-SFS remnant considerations were based on standard cut-off- RVBWR and RV/TLV. Non-congestive RVBWR was based on non-congestive RV.RESULTS: MHV and non-MHV remnants showed no significant differences in RV, RV/TLV, RVBWR, total bilirubin, or INR. SFS-remnants with RV/TLV < 30%and non-SFS-remnants with RV/TLV ≥ 30% showedno significant differences either. RV and RVBWR for non-MHV(n = 59) and MHV-containing(n = 12)remnants were 550 ± 95 ml and 0.79 ± 0.1 ml vs568 ± 97 ml and 0.79 ± 0.13, respectively(P = 0.423 and P = 0.919. Mean left RV/TLV was 35.8% ± 3.9%.Non-MHV(n = 59) and MHV-containing(n = 12)remnants(34.1% ± 3% vs 36% ± 4% respectively,P = 0.148. Eight SFS-remnants with RVBWR < 0.65 had a significantly smaller RV/TLV than 63 non-SFSremnants with RVBWR ≥ 0.65 [SFS: RV/TLV 32.4%(range: 28%-35.7%) vs non-SFS: RV/TLV 36.2%(range: 26.1%-45.5%), P < 0.009. Six SFS-remnants with RV/TLV < 30% had significantly smaller RVBWR than 65 non-SFS-remnants with RV/TLV ≥ 30%(0.65(range: 0.6-0.7) vs 0.8(range: 0.6-1.27), P < 0.01.Two(2.8%) donors developed reversible liver failure.RVBWR and RV/TLV were concordant in 25%-33%of SFS and in 92%-94% of non-SFS remnants. MHV management options including complete MHV vs MHV-4A selective retention were necessary in n = 12 vs n =2 remnants based on particularly risky congestive and non-congestive volume constellations.CONCLUSION: MHV procurement should consider individual remnant congestive- and non-congestive volume components and anatomy characteristics,RVBWR-RV/TLV constellation enables the identification of marginally small remnants.