Nagy Habib

Endoscopically applied radiofrequency ablation appears to be safe in the treatment of malignant biliary obstruction

BACKGROUNDnIn unresectable malignant bile duct obstruction in a patient with a life expectancy longer than 3 months, the use of self-expandable metal stents (SEMSs) is the standard technique to ensure continued biliary drainage. As many as 50% of patients with SEMSs will present with stent occlusion within 6 months. Changes to stent design and composition and concomitant therapy have failed to improve stent patency; therefore, alternative techniques to safely prolong stent patency are required.nnnOBJECTIVEnTo demonstrate the safety of endobiliary bipolar radiofrequency ablation (RFA) in patients with malignant biliary obstruction and to report the 90-day biliary patency of this novel procedure.nnnDESIGNnOpen-label pilot study.nnnSETTINGnSingle tertiary care unit.nnnPATIENTSnA total of 22 patients with unresectable malignant bile duct obstruction.nnnINTERVENTIONSnBipolar RFA within the bile duct.nnnMAIN OUTCOME MEASUREMENTSnImmediate and 30-day complications and 90-day stent patency.nnnRESULTSnA total of 22 patients (16 pancreatic, 6 cholangiocarcinoma) were recruited between January 2009 and April 2010. Deployment of an RFA catheter was successful in 21 patients. SEMS placement was achieved in all cases of successful RFA catheter deployment. One patient failed to demonstrate successful biliary decompression after SEMS placement and died within 90 days. All other patients maintained stent patency at 30 days. One patient had asymptomatic biochemical pancreatitis, 2 patients required percutaneous gallbladder drainage, and 1 patient developed rigors. At 90-day follow-up, 1 additional patient had died with a patent stent, and 3 patients had occluded biliary stents.nnnLIMITATIONSnCohort study.nnnCONCLUSIONSnEndobiliary RFA treatment appears to be safe. Randomized studies with prolonged follow-up are warranted.

Analysis of Endoscopic Radiofrequency Ablation of Biliary Malignant Strictures in Pancreatic Cancer Suggests Potential Survival Benefit

AbstractBackgroundPancreatic carcinoma is often inoperable, carries a poor prognosis, and is commonly complicated by malignant biliary obstruction. Phase I/II studies have demonstrated good safety and early stent patency using endoscopic biliary radiofrequency ablation (RFA) as an adjunct to self-expanding metal stent (SEMS) insertion for biliary decompression.AimTo analyze the clinical efficacy of endobiliary RFA.MethodsnRetrospective case–control analysis was carried out for 23 patients with surgically unresectable pancreatic carcinoma and malignant biliary obstruction undergoing endoscopic RFA and SEMS insertion and 46 controls (SEMS insertion alone) in a single tertiary care center. Controls were stringently matched for age, sex, metastases, ASA/comorbidities. Survival, morbidity, and stent patency rates were assessed.ResultsRFA and control groups were closely matched—ASA 2.35xa0±xa00.65 versus 2.54xa0±xa00.50, pxa0=xa00.086; metastases 9/23 (39.1xa0%) versus 18/46 (39.1xa0%), pxa0=xa00.800; chemotherapy 16/23 (69.6xa0%) versus 24/46 (52.2xa0%), pxa0=xa00.203. Median survival in RFA group was 226xa0days (IQR 140–526xa0days) versus 123.5xa0days (IQR 44–328xa0days) in controls (pxa0=xa00.010). RFA was independently predictive of survival at 90xa0days (OR 21.07, 95xa0% CI 1.45–306.64, pxa0=xa00.026) and 180xa0days (OR 4.48, 95xa0% CI 1.04–19.30, pxa0=xa00.044) in multivariate analysis. SEMS patency rates were equivalent in both groups. RFA was well tolerated with minimal side effects.ConclusionsEndoscopic RFA is a safe and efficacious adjunctive treatment in patients with advanced pancreatic malignancy and biliary obstruction and may confer early survival benefit. Randomized prospective clinical trials of this new modality are mandated.

Embolization of Hepatic Arterial Branches to Simplify Hepatic Blood Flow Before Yttrium 90 Radioembolization: A Useful Technique in the Presence of Challenging Anatomy

PurposeIn the presence of variant hepatic arterial anatomy, obtaining whole-liver coverage with yttrium 90 (Y90) radioembolization may be challenging. The purpose of this study was to determine whether a technique whereby variant hepatic arterial branches are embolized and then Y90 is administered selectively into one remaining hepatic arterial branch results in whole-liver coverage and effective therapy. A retrospective comparison of treatment response was made between a group of patients who underwent this technique before Y90 administration and a group of patients who received standard Y90 administration as a single dose into the proper hepatic artery or in divided doses into the immediate hepatic artery branches. The rest of the workup and treatment were identical in both groups, including routine embolization of potential nonhepatic, nontarget vessels (e.g., the gastroduodenal artery).MethodsA total of 32 patients (mean age 56.9xa0years, range 39–77xa0years) treated with Y90 between June 2004 and March 2008 were analyzed. The primary malignancy was colorectal in 29, breast in 2, and cholangiocarcinoma in 1. Group 1 comprised 20 patients who had no alterations to their hepatic arterial supply. Group 2 comprised 12 cases who had undergone prior embolization of hepatic arterial branches before administration of Y90. The response to treatment was assessed by comparing standardized uptake value (SUV) on the pre- and postprocedure fludeoxyglucose positron emission tomographic studies of representative lesions within the right and left lobes of the liver.ResultsIn group 1, significant response (Pxa0<xa00.001) was seen among right lobe lesions but not among left lobe lesions (Pxa0=xa00.549). In group 2, there was a significant response among both right (Pxa0=xa00.028) and left (Pxa0=xa00.014) lobe lesions. No difference was found in the response of right lobe lesions (Pxa0=xa00.726) between groups 1 and 2; a significantly greater response was found in group 2 compared to group 1 (Pxa0=xa00.004) for left lobe lesions.ConclusionSelective Y90 radioembolization after manipulation of hepatic arterial blood supply leads to an even distribution within the entire liver. When variations in hepatic arterial anatomy exist, this technique allows effective whole-liver radioembolization therapy from a single selective arterial injection.

Reactive Lymphoid Hyperplasia of the Pancreas: A Clinical Conundrum

CONTEXTnLocalized reactive lymphoid hyperplasia is a rare condition characterized by the presence of lymphoid follicles.nnnCASE REPORTnWe describe a case of a 60-year-old woman who presented with right upper quadrant pain and was found to have a reactive nodular hyperplasia of the pancreas involving the uncinate process, body and tail of the gland. Due to the multifocal distribution of these hypoechoic vascular lesions, a total pancreatectomy was performed since malignancy could not be safely excluded.nnnCONCLUSIONnThere have been a handful of cases reporting reactive lymphoid hyperplasia affecting the pancreas; however, it is uncommon to perform such a radical pancreatic resection for this benign condition.

OC-075 Analysis of Long-Term outcomes after Endoscopic Radiofrequency Ablation for Bile Duct Strictures in Pancreatic Malignancy Suggests Potential Survival Benefit

Introduction Pancreatic carcinoma carries a poor prognosis with only 10–20% of patients amenable to attempts at curative surgery at presentation. Biliary obstruction is a common complication and many patients will require self-expanding metal stent (SEMS) insertion for definitive decompression. A recent pioneering phase I/II study in our tertiary referral centre demonstrated excellent safety and 90d stent patency with endobiliary radiofrequency ablation (RFA) as an adjunct to SEMS insertion. The longer-term impact of this novel endoscopic treatment modality on biliary drainage and patient survival in advanced pancreatic carcinoma is unknown. Objective To investigate the longer-term efficacy of endobiliary RFA in the management of malignant bile duct obstruction associated with inoperable pancreatic carcinoma. Methods Retrospective cohort analysis of 23 patients with unresectable pancreatic carcinoma undergoing RFA + SEMS insertion, and 46 matched controls undergoing SEMS insertion alone, for malignant biliary obstruction in a single tertiary referral centre. Patients were stringently matched for age, sex, metastases, ASA/co-morbidities, and intention to treat with palliative chemotherapy. Survival, maintenance of stent patency, and procedure-related complications were assessed. Results RFA and control groups were closely matched- age 68.9 +/- 9.0y vs. 69.8 +/- 9.9y, p = 0.791; ASA 2.35 +/- 0.65 vs. 2.54 +/- 0.50, p = 0.086; metastases at treatment 9/23 (39.1%) vs. 18/46 (39.1%), p = 0.800; chemotherapy 16/23 (69.6%) vs. 24/46 (52.2%), p = 0.203. Median survival was 227d after RFA vs. 123.5d in controls (HR 0.633 CI 0.378–1.060, p = 0.011). RFA was independently predictive of survival at 90d (OR 16.14, CI 1.35–193.18, p = 0.028) and 180d (OR 4.25, CI 1.00–18.01, p = 0.049). Overall SEMS patency rates were the same across both groups, though more patients were alive with a patent index SEMS after RFA within the first few months (73.9% vs. 41.3% at 4.5 m, p = 0.012). Complications of RFA were few (1 pancreatitis, 1 cholangitis), with a median post-procedure inpatient stay of 1d (1–8). Conclusion In the single largest case series to date, endobiliary RFA was found to be a safe and efficacious adjunctive treatment in the management of patients with advanced pancreatic malignancy and biliary obstruction, and demonstrated potential early survival benefit. These data suggest that endobiliary RFA could be an additional treatment option in advanced pancreatic carcinoma, and form the basis from which future prospective clinical trials of this novel treatment modality can be designed. Disclosure of Interest Y. Kallis: None Declared, N. Phillips: None Declared, A. Steel: None Declared, H. Kaltsidis: None Declared, J. Nicholls Shareholder of: EMcision Ltd UK, L. Jiao: None Declared, P. Vlavianos: None Declared, N. Habib Shareholder of: EMcision Ltd UK, D. Westaby: None Declared.

MicroRNA-181a* targets nanog in a subpopulation of CD34+ cells isolated from peripheral blood

Background and Objectives: Hematopoietic stem cells (HSC) are the most widely studied and characterized adult stem cells, which play an essential role in sustaining the formation of blood and immune system. The ease of their manipulation, the lack of serious ethical issues, and, in the autologous setting, the absence of their immunogenicity, have made them an attractive tool for developing stem cell-based therapies. Exploiting the properties of HSC by microRNA (miRNA) profiling offers an attractive approach to identify new regulators of stem cell fate. Although numerous miRNA have been screened from hematopoietic stem cells (HSC), the targets corresponding to many of these miRNA have not yet been fully elucidated. Therefore the objective of this study is to generate a miRNA profile from a subpopulation of adherent CD34+ HSC isolated from G- colony-stimulating factor mobilized peripheral blood aiming to understand the role of selected miRNA in regulating HSC stemness. Methods: CD34+ cells from patients blood were isolated using a CD34+ isolation kit (Miltenyi Biotec) according to the manufacturers protocol. miRNA profiling of adherent and nonadherent CD34+ cells was done using TaqMan Array MicroRNA Cards. Nanog expression levels was tested using a dual-luciferase reporter construct for miR-181a* or its mutant variant and Nanog 3′ UTR mRNA. Results: In this study, we have identified eight clusters of miRNA that were differentially expressed in an adherent subpopulation of CD34+ stem cells. Further analysis of one of the clusters by bioinformatics revealed that a miRNA, miR-181a*, which is highly expressed in the adherent CD34+ cells, affects the expression levels of Nanog, a stem cell surrogate marker. We show specifically by reporter assay and mutational analysis that miR-181a* targets a seedless 3′ compensatory site in the 3′UTR of Nanog and affects gene expression. We demonstrate that inhibiting miR-181a* upregulates the Nanog expression level, in addition to an increase in alkaline phosphatase activity. Conclusions: In conclusion, our results highlight a new stem cell-related target for the miR-181 family and show that miR-181a* directly targets Nanog in a subpopulation of CD34+ stem cells suggesting a possible role of miR-181a* in regulation of adherent CD34+ HSC cells stemness.

P20 First report of the long-term efficacy of a novel endoscopic radiofrequency ablation technique for malignant biliary obstruction

Introduction Insertion of self-expanding metal stents (SEMS) is standard practice in patients with unresectable malignant biliary strictures. Stent occlusion is a significant clinical problem in patients surviving beyond 3u2005months. A pioneering phase I/II study in our tertiary referral centre demonstrated good safety and 30-day patency using a novel endoscopic radiofrequency ablation (RFA) technique as an adjunct to SEMS.1 The longer term impact of combined RFA+SEMS on biliary drainage and overall patient survival is unknown. Aim To investigate long-term safety and efficacy of endobiliary RFA in malignant bile duct obstruction. Method Retrospective cohort analysis of 24 patients undergoing RFA+SEMS (17 pancreatic carcinoma; 7 cholangiocarcinoma) and 44 matched controls undergoing SEMS insertion alone (34 pancreatic carcinoma, 10 cholangiocarcinoma) for malignant biliary obstruction in a single tertiary referral centre. Patients were matched for age, sex, disease, presence of metastases, ASA/co-morbidities, and intention to treat with palliative chemotherapy. Patients with a potential minimum of 6-month follow-up were included and survival, maintenance of stent patency and procedure-related complications were assessed. Results RFA treated and control cohorts were closely matched- mean age 71.8±9.8u2005yrs vs 68.8±10.3, metastases at treatment 9/24 (38%) vs 17/44 (39%), chemotherapy 16/24 (67%) vs 27/44 (61%). Kaplan–Meier analysis showed a median survival of 227u2005days in the RFA group vs 159 days in controls (p=0.067). Multivariate analysis showed RFA treatment to be the strongest predictor of survival at 90u2005days (OR 26.1, p=0.011). Survival benefits may extend beyond 90u2005days (OR 2.8, p=0.071 at 180u2005days; OR 2.8, p=0.102 at 360u2005days), but require further investigation. Within 6u2005months after treatment, more patients were alive with a patent first SEMS in the RFA cohort than in controls. Complications of RFA were few (1 pancreatitis, 2 cholecystitis) and comparable to those associated with standard ERCP alone. The procedure was well-tolerated with a median post-procedure inpatient stay of 1u2005day (1–24). Conclusion In the single largest case series studied to date, endobiliary RFA is a safe and efficacious treatment for malignant biliary obstruction, with potential early survival benefit. Large multi-centre prospective trials of this novel treatment modality are warranted.Abstract P20 Figure 1 Kaplan–Meier survival analysis.