Pancreatobiliary Malignancies Research Articles

Cancer cell-induced neutrophil extracellular traps promote both hypercoagulability and cancer progression.

IntroductionNeutrophils can generate extracellular net-like structures by releasing their DNA–histone complexes and antimicrobial peptides, which is called neutrophil extracellular traps (NETs). Various stimuli can induce NET formation. In particular, neutrophils and NET formation are abundant in tumor tissue. This study investigated how cancer cells induce NET formation and whether this NET formation promotes plasma thrombin generation and cancer progression.MethodsInduction of NET formation by a pancreatic cancer cell line (AsPC-1) was assessed by measuring the histone–DNA complex level. The endogenous thrombin potential (ETP) was measured by thrombin generation assay. In vitro migration, invasion, and tubule formation assays were performed. The circulating levels of NET markers and hypercoagulability markers were assessed in 62 patients with pancreatobiliary malignancy and 30 healthy controls.ResultsAsPC-1 significantly induced NET formation in a dose-dependent manner. Conditioned medium (CM) from AsPC-1 also induced NETs. Interestingly, NET-formation was abolished by heat-inactivated CM, but not by lipid-extracted CM, suggesting an important role of protein components. A reactive oxygen species inhibitor did not inhibit cancer cell–induced NET formation, but prostaglandin E1 (PGE1, cyclic adenosine monophosphate inducer) and antithrombin did. NETs significantly increased ETP of normal plasma. Of note, NETs promoted cancer cell migration and invasion as well as angiogenesis, which were inhibited by histone-binding agents (heparin, polysialic acid), a DNA-degrading enzyme, and Toll-like receptor neutralizing antibodies. In patients with pancreatobiliary malignancy, elevated NET markers correlated well with hypercoagulability makers.ConclusionOur findings indicate that cancer cell–induced NET formation enhances both hypercoagulability and cancer progression and suggest that inhibitors of NET formation such as PGE1 and antithrombin can be potential therapeutics to reduce both hypercoagulability and cancer progression.

Analysis of microRNA expression in brush cytology specimens improves the diagnosis of pancreatobiliary cancer

Background/ObjectivesMalignant pancreatobiliary strictures are in many cases clinically indistinguishable and present a major problem to endoscopy specialists. Intraductal sampling procedures such as brush cytology are commonly used for diagnosis with a sensitivity that is low for a diagnostic test used in daily clinical practice. MicroRNA (miR) alterations detected in many cancers are disease-specific, which can be utilized in clinical applications. The aim of the present study was to analyze whether determination of miR expression levels in intraductal brush cytology specimens is a feasible approach to improve the diagnosis of pancreatobiliary cancer. MethodsBrush cytology specimens have been collected during endoscopic retrograde cholangio-pancreatography (ERCP) and analyzed by routine cytology and ancillary miR assays. Total RNA was extracted using the miRNeasy Mini Kit and the expression of miRs frequently dysregulated in pancreatobiliary cancer (miR-16, miR-21, miR-196a, miR-221) were analyzed by quantitative real-time PCR using RNU6B as internal control. ResultsRoutine cytology resulted in no false positive diagnoses, however, the combined sensitivity remained at 53.8%. Expression (ΔCt values) of miR-16 (p = 0.0039), miR-196a (p = 0.0003) and miR-221 (p = 0.0049) showed a clear statistical significance between malignant and benign pancreatobiliary specimens (n = 35). Malignancy could be detected combining routine cytology and the miR-196a single marker expression levels with a sensitivity of 84.6% (92.9% in biliary strictures) with no false positives. ConclusionsThe results offer the first direct demonstration that microRNAs are readily detectable in brush cytology specimens obtained during ERCP, and have the potential to help the cytological diagnosis of pancreatobiliary malignancy.

Endoscopic Palliation for Biliary and Pancreatic Malignancies: Recent Advances.

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.

Double Duct Sign and Elevated CA 19-9 - Clinical Correlation Is Always Needed

The “double duct sign” describes radiographic evidence of dilatation of both the common bile duct (CBD) and pancreatic duct. This sign tends to be an alarming finding, as it is highly associated with malignancy, particularly tumors of the pancreatic head. Similarly, CA 19-9 is a serologic marker used in diagnosing and monitoring malignant disease of the pancreas, gallbladder, and bile duct. While both the double duct sign and CA 19-9 are associated with malignancy, they are also less commonly associated with benign conditions. A 70 year-old-male with hypertension and coronary artery disease presented with 3 days of colicky right upper quadrant abdominal pain and confusion. He was found to be febrile, tachycardic, and tachypneic. His exam was notable for jaundice and a mildly distended, but soft abdomen with moderate tenderness in the right upper quadrant. His labs were significant for leukocytosis to 24.0 103 ml, aspartate aminotransferase 220 IU/L, alanine aminotransferase 346 IU/L, alkaline phosphatase 363 IU/L, total bilirubin 15.1 mg/dL, direct bilirubin 14.1 mg/dL, and lipase 119 U/L. His CT abdomen/pelvis revealed pancreatic inflammation, a dilated pancreatic duct (9 mm), CBD of 1.8 cm, and a 1.1 cm hyperdensity within the CBD. Findings were concerning for a pancreatic head mass. CA 19-9 was 17,788 U/mL. Endoscopic retrograde cholangiopancreatography (ERCP) was notable for a large stone obstructing the ampulla and biliary sphincterotomy and stone extraction was performed. He improved clinically and his CA 19-9 was 535 on the day of discharge. Eight weeks later, a repeat pancreatobiliary endoscopic ultrasound and ERCP showed a main pancreatic duct of 2.5 mm and CBD of 7 mm. There was no evidence of abnormality or mass in the pancreatic head, body, or tail. The double duct sign is highly associated with malignancy, with reported prevalence of malignancy in 58-100% of patients. CA 19-9 is a serologic marker used to aid in the diagnosis and monitoring of malignancy of the pancreas, gallbladder, and bile duct. Elevated levels of CA 19-9 have also been associated with benign conditions, notably acute cholangitis and choledocholithiasis, and there is one case report that describes a patient with double duct sign from choledocholithiasis. To our knowledge, this is the only report of a case of a patient with obstructive jaundice, elevated CA 19-9, and double duct sign that was not found to have an underlying pancreatobiliary malignancy.

Dysplasia in Gallbladder: What Should We Do?

IntroductionOn occasional cholecystectomies, pathologists encounter incidental dysplasia in the gallbladder mucosa in the sections submitted per protocol for histologic examination. If dysplasia is identified, additional sections are taken and/or the gallbladder is entirely submitted to rule out underlying adenocarcinoma. The aim of our study was to assess the incidence of subsequent identification of invasive adenocarcinoma on additional sections, after an incidentally detected dysplasia was noted on a routine cholecystectomy section. We also aimed to study the significance of the incidental detection of dysplasia and adenocarcinoma, as well as showing the association of gallbladder dysplasia to synchronous or metachronous dysplasia/neoplasia in the biliary tract. Material and MethodsOur study was approved by the Institutional Review Board. We retrospectively identified 41 consecutive cases of routine cholecystectomies from 1991 to 2017, which had no clinical suspicion of neoplasia, and did not have any identifiable mass lesion, but on histopathologic analysis, had neoplasia (adenocarcinoma in 4 cases, and dysplasia in 37 cases). The pathologies of all cases were reviewed, and the diagnosis and grade of dysplasia were confirmed. The clinical information was obtained from the electronic medical records. ResultsOf the 37 cases with dysplasia, 10 (27%) had high-grade dysplasia (HGD) and the remaining showed low-grade dysplasia (LGD). All 4 cases of adenocarcinoma had some gross abnormalities (such as porcelain gallbladder, or ruptured, thickened, and roughened walls, or a granular mucosa). In contrast, none of the 37 cases with dysplasia had any gross abnormality. In 24 (of 37) cases of dysplasia, additional sections were submitted (median 8; ranging from 2 to 29), and in 11 cases, the gallbladder was entirely submitted. None of these cases showed any additional pathologic finding on the extra sections. Interestingly, 7 cases with dysplasia (18.9%; 6 LGD and 1 HGD) were associated with a concomitant pancreatobiliary malignancy. For the remaining 30 cases, follow-up information was available in 16 cases (53.3%) with a mean follow-up of 76.5 months (ranging from 12 to 204 months). None of these showed any subsequent development of pancreatobiliary neoplasms. ConclusionIncidentally detected gallbladder dysplasia in a cholecystectomy specimen, without any gross abnormality, has almost no risk of a hidden invasive carcinoma. Although cholecystectomy is sufficient treatment for gallbladder dysplasia, in our study cohort, 18.9% of cases with incidental dysplasia in gallbladder had an associated pancreatobiliary carcinoma, which supports the hypothesis of multifocal neoplastic potential in the pancreatobiliary tree (also known as field effect). Although follow-up on 16 cases shows no subsequent development of any other pancreatobiliary neoplasm, this number is probably not enough to rule out a serial imaging follow-up of patients who have reported dysplasia in their gallbladder, to assess for subsequent development of neoplasia elsewhere in the pancreaticobiliary tree.

FLT-PET CT Scan can avoid radical surgery in masquerading pancreatobiliary lesions

Background: The purpose of this study was to evaluate the efficacy of this marker (FLT-PET CT scan) and to compare it with FDG-PET scan in differentiating benign from malignant diseases in suspected bilio-pancreatic tumors. Methodology: It is a prospective observational study from July 2013 to April 2017. Suspected Pancreaticobiliary malignancies were included. FDG-PET/CT and FLT-PET/CT was done. Histopathology of the resected specimen or FNAC was considered the gold standard for diagnosis. Results: Fifty-six patients harboring 58 suspected lesions of pancreatobiliary malignancy were included in this study Two patients had synchronous lesions in gall bladder and pancreas. Majority of patients(75.8%,44/58) had gall bladder carcinoma. Thirty-five patients underwent laparotomy, thirty of them were resorted to radical surgery. Eighteen lesions(31%) were confirmed as benign(XGC+Chr. Cholecystitis=14, Ch.Pancreatitis+Pancreatic lipodystrophy=4) on histological examination. The result of FLT-PET were better than FDG-PET. The sensitivity, specificity, PPV and NPV & accuracy of FLT-PET was 92.5%, 100%, 100%, 84.2% and 94.6% respectively. The sensitivity, specificity, PPV and NPV & accuracy of FDG-PET was 97.5%, 31.2%, 78%, 83.3% and 78.5% respectively. Adding CA19-9 for detecting malignancy accuracy increases to 98.2%. On analyzing with ROC, at SUVmax = 2 on FLT-PET, the sensitivity and specificity for detecting malignancy in all pancreaticobiliary lesions was 92.5% and 100% respectively(AUC = 0.91). AUC for FDG-PET CT in pancreaticobiliary lesions was 0.624. Conclusion: FLT-PET is better than FDG-PET scan in differentiating benign pancreaticobiliary lesions. By employing FLT-PET CT as the diagnostic tool, it is predicted that 43.3% of radical surgery done for benign bilio-pancreatic lesions can be avoided.

Randomized controlled trial of intraoperative chemical splanchnicectomy for patients with resected pancreatobiliary malignancies

Introduction: This prospective double-blind placebo controlled trial studied the benefits of intraoperative celiac neurolysis for durable postoperative pain control, long-term quality of life and survival for patients with resected pancreatobiliary cancer. Method: Chemotherapy naïve patients undergoing resection for pancreatic adenocarcinoma or distal cholangiocarcinoma were randomized to receive either 50% ethanol (E) or saline (S) injection of the celiac plexus during pancreatoduodenectomy (PD). The primary study endpoint was postoperative pain severity over two years from randomization. Secondary endpoints included pain interference with daily life and overall survival. Results: Patient and disease characteristics between the two treatment groups are summarized in the table. Adverse events related to treatment did not differ between the two groups within 90 days of operation. Postoperative delayed gastric emptying was observed in 4 (14%) pts in the E group compared to 9% in the S group, p = 0.24. The mean pain severity at 12 mos for the E and S groups was 2.12 vs 2.42, p = 0.65, with no significant increases over respective baseline preoperative pain severity. Mean pain interference with daily life did not differ between the two treatments at any 3 month interval over two years. Actual survival for the entire study population at 2 yrs was 35%. Ethanol injection of the celiac plexus did not influence the timing or pattern of tumor recurrence, H.R.1.21, p = 0.57. Conclusions: Intraoperative chemical splanchnicectomy during PD for resectable pancreatobiliary cancer is safe but does not benefit patients with regards to long-term pain control, pain interference with daily life, or disease-free survival.Tabled 1TableE Group (N = 23)S Group (N = 28)P-valueMean age +/– SEM63.4y ± 1065.3y ± 9.70.63Preop pain – Low20 (87%)22 (79%)0.49Preop pain – Mod/High3 (13%)6 (21%)0.49Tumor site – Pancreas21 (91%)25 (89%)0.67T stage – pT320 (87%)24 (86%)0.61N stage – pN119 (83%)19 (68%)0.33R0 margin status18 (78%)24 (85%)0.71Perineural invasion18 (78%)25 (89%)0.24Histologic grade – G319 (83%)19 (68%)0.29 Open table in a new tab

An Alternative Technique in the Detection of Pancreatobiliary Malignancy: Computer-Assisted Wide Area Transepithelial Sampling

Gastroenterology Medicine & Research An Alternative Technique in the Detection of Pancreatobiliary Malignancy: Computer-Assisted Wide Area Transepithelial Sampling Samson Ferm*, Constantine Fisher, Frances Puello, Moshe Rubin, Syed Hussain, Sang Kim New York Presbyterian Queens, USA *Corresponding author: Samson Ferm, New York Presbyterian Queens, 56-45 Main St. Flushing New York, 11375, USA Submission: November 02, 2018; Published: February 21, 2018 DOI: 10.31031/GMR.2018.01.000511 ISSN 2637-7632Volume1 Issue3

Endoscopic Management of Pancreatobiliary Neoplasms

Endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) are the mainstays of interventional endoscopic practice. EUS occupies a central role in the diagnosis of pancreatobiliary neoplasms and offers a platform for a wide range of direct tumor therapies. Initial steps have demonstrated the feasibility of such applications in animal models and pilot studies. Larger clinical trials and incorporation of EUS-based therapies into cooperative cancer studies might demonstrate an impact in the clinical prognosis of patients with pancreatic cancer. ERCP plays an important role in elucidating indeterminate biliary strictures and in treating patients with malignant biliary obstruction who are symptomatic or have borderline-resectable or unresectable disease. ERCP-directed ablative therapies enable neoadjuvant and palliative intervention in patients with malignant biliary obstruction, in particular perihilar cholangiocarcinoma. Additional comparative, multicenter studies are needed to better understand the safety and efficacy of endobiliary brachytherapy, photodynamic therapy, and radiofrequency ablation in patients with pancreatobiliary malignancies.

Diabetes and the Pancreatobiliary Diseases.

The emphasis of this review article is to bring to the forefront the spectrum of pancreatobiliary disorders and their association with diabetes. We hope to systematically discuss the link between diabetes and disorders of the pancreas including acute and chronic pancreatitis, as well as pancreatic cancer. We also hope to review and highlight the literature with respect to other cancers of the biliary tree including gallbladder and cholangiocarcinoma. Lastly, we discuss diabetes and biliary dyskinesia. Newer cohort studies suggest the presence of diabetes to increase the severity and worsen outcomes in acute pancreatitis. Post pancreatitis diabetes is a novel disease entity being increasingly recognized. The use of pancreatic enzyme replacement therapy (PERT) in chronic pancreatitis may attenuate the risk of endocrine dysfunction. Pancreatic cancer may either be the consequence of diabetes or a presenting manifestation. The use of anti-diabetic medications may confer protection against development of pancreatic cancer. Gallbladder adenocarcinoma and cholangiocarcinoma risks are elevated in those with underlying diabetes. Diabetes can directly impact or deteriorate outcome of acute and chronic pancreatitis and well as pancreatobiliary malignancies. It could also occur as a result of loss of endocrine function after pancreatitis. Like many areas of the digestive tract, biliary motility could be impacted by diabetes.

Annexin A11 is targeted by IgG4 and IgG1 autoantibodies in IgG4-related disease

ObjectiveImmunoglobulin G4-related disease (IgG4-RD) is a multiorgan immune-mediated disease that predominantly affects the biliary tract (IgG4-associated cholangitis, IAC) and pancreas (autoimmune pancreatitis, AIP). We recently identified highly expanded IgG4+ B-cell...

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IgG4-related disease of the biliary tract and pancreas: clinical and experimental advances.

IgG4-related disease (IgG4-RD) is an immune-mediated disease of unknown cause. It predominantly affects the biliary tract [IgG4-associated cholangitis (IAC)] and pancreas [autoimmune pancreatitis (AIP)] of mostly elderly men. Accurate diagnostic tests are lacking. Patients benefit from predniso(lo)ne treatment. However, disease relapse is often seen. This review will address pathophysiological aspects and advances in diagnostic and therapeutic strategies. The role of IgG1 and IgG4 in the pathophysiology of IgG4-RD was studied in mice which showed more intense organ damage of pancreas and salivary glands when IgG1 rather than IgG4 of patients with IgG4-RD was injected. Coadministration of IgG1+IgG4 led to dampening of IgG1-mediated injury supporting the view that IgG4 exerts immune-dampening effects. IgG4+ B-cell receptor clones identified by next-generation sequencing and the IgG4/IgG RNA ratio in human blood assessed by quantitative PCR were able to accurately distinguish IAC/AIP from primary sclerosing cholangitis or pancreatobiliary malignancies. Long-term treatment with low-dose prednisolone was safe and reduced the number of flare-ups in patients with AIP. Early diagnosis by a novel accurate and easy-to-use qPCR test may prevent life-threatening complications, unnecessary interventions and fatal course because of misdiagnosis. Prednisolone treatment remains the standard of care in patients with IgG4-RD.

Diagnostic Accuracy of Serum Carbohydrate Antigen 19-9 in Determining Etiology of Obstructive Jaundice

Background: Serum carbohydrate antigen 19-9 (CA 19-9), a tumour marker for malignancies of the hepatobiliary tract and pancreas, frequently elevated in a number of non-malignant conditions that are associated with jaundice. The CA 19-9 tends to normalize following the restoration of biliary drainage. This study was designed to assess the clinical application of CA19-9 in diagnosing pancreatobiliary malignancies in patients with obstructive jaundice and in discriminating between benign and malignant causes.Methods: Sixty three patients presented with obstructive jaundice on the basis of clinical, biochemical and imaging methods with elevated CA 19-9 were included in this study. Serum CA 19-9 levels were measured on admission and two weeks following endoscopic biliary drainage performed through an ERCP procedure at the department of Gastrointestinal, hepatobiliary and pancreatic disorders (GHPD) of BIRDEM general hospital. Malignant and benign cases were differentiated by ultrasonogram, CT scan, MRCP and morphological findings during ERCP procedure. Diagnostic accuracy of CA19-9 in the detection of malignancy was estimated by the receiver operating characteristic (ROC) curve.Results: Age was 53.76±14.48 years (mean±SD) and sex was 32:31 (M:F). Median value of CA 19-9 in malignant cases was higher (1000 U/ml) than benign cases (93 U/ml) (p=0.001). After biliary drainage serum CA19-9 levels normalized in 15(50%) benign and 1(3%) malignant cases (p=0.001). The AUC of CA 19-9 was 0.825. Sensitivity, specificity, PPV and NPV at cut off value 90 U/ml were 100, 50, 68.8 and 100; at 100 U/ml were 100, 53.3, 70.2 and 100; at 200 U/ml were 90.9, 66.7, 75 and 87, at 500 U/ml were 63.6, 76.7,75 and 65.7 respectively. Diagnostic accuracy of CA 19-9 was observed more at cut off value 200 U/ml.Conclusions: Deranged CA19-9 is frequently observed in benign conditions with jaundice and shown to normalize following improvement of biliary drainage. Caution is necessary in the interpretation of an elevated serum CA 19-9 value as a marker for malignancy, especially in patients with benign cholestasis.Birdem Med J 2017; 7(2): 95-100

Double immunostaining for maspin and p53 on cell blocks increases the diagnostic value of biliary brushing cytology.

Our objective is to elucidate the usefulness of maspin/p53 double immunostaining on biliary brushing cytology specimens. We first examined the expression of maspin in the biliary epithelium with variable degrees of dysplasia using surgically resected specimens (n = 56). Maspin appeared to be overexpressed in a stepwise manner from benign to malignant cholangiocytes: the reactive epithelium (20%), biliary intraepithelial neoplasia (~50%), and invasive cholangiocarcinomas (>90%). Next, an automated sequential double immunostaining protocol for maspin and p53 was applied to paraffin-embedded cell blocks of the biliary brushing cytology specimens obtained from 58 consecutive patients. Cell block preparation was successful in 44 cases (76%), which were morphologically diagnosed as adenocarcinoma (n = 16), atypical cells not diagnostic for malignancy (n = 10), and benign (n = 18). Double positive cells were observed in 14/16 (88%) morphologically malignant, 6/10 (60%) borderline, and 0/18 benign cases. All 20 positive cases were proven to have pancreatobiliary malignancies by subsequent imaging or pathological analyses. A similar staining protocol for S100P and p53 was also applied to the same cohort; however, the positive frequency was slightly lower than those of maspin and p53 (36% vs. 45%). In conclusion, Maspin/p53 double immunostaining on cell blocks contributes to the detection of malignant cells in biliary brushing cytology specimens.

Clinical Interpretation of Elevated CA 19-9 Levels in Obstructive Jaundice Following Benign and Malignant Pancreatobiliary Disease.

Elevated carbohydrate antigen (CA) 19-9 level may be unable to differentiate between benign and malignant pancreatobiliary disease with obstructive jaundice. The study aims to determine the clinical interpretation and the diagnostic value of CA 19-9 level in pancreatobiliary diseases with coexistent obstructive jaundice. We retrospectively reviewed the data of 981 patients who underwent biliary drainage due to obstructive jaundice following pancreatobiliary disease at Sanggye Paik Hospital for 5 years. 114 patients with serial follow-up data for CA 19-9 level were included in this study (80 patients with malignancy and 34 patients with benign diseases). We compared the levels of CA 19-9 levels and the biochemical value before and after biliary drainage. The rate of CA 19-9 elevation (>37 U/mL) was significantly different between the benign group and the malignant group (59% vs. 90%, p=0.001). Despite the decrease in serum bilirubin after biliary drainage, CA 19-9 levels remained elevated in 12% of patients in the benign group and in 63% of patients in the malignant group (p<0.001). Finally, 12% of patients in the benign group turned out to have malignant disease. A receiver operating characteristic analysis provided a cut-off value of 38 U/mL for differentiating benign disease from malignant disease after biliary drainage (area under curve, 0.787; 95% confidence interval, 0.703 to 0.871; sensitivity, 62%; specificity, 88%). This study suggested that we should consider the possibility of malignant causes if the CA 19-9 levels remain high or are more than 38 U/mL after resolution of biliary obstruction.

Gender and Ethnic Variations of Biliary Dilatation in Individuals on Methadone Maintenance Treatment: A Retrospective Observational Study in Inner City Population

Introduction: Individuals with opioid dependency has been traditionally treated with Methadone in drug rehabilitation programs. Biliary dilatation can result from several pancreto-biliary diseases including choledoholithiasis and malignancies. However, non-pathological dilatation of biliary duct can result from chronic methadone use. We designed our study to evaluate gender and ethnic variations of biliary dilatation in individuals on Methadone Maintenance Treatment (MMT). Methods: We conducted cross sectional observational study of all patients admitted to out hospital who are currently enrolled in MMT program and receiving methadone. We excluded patients taking methadone for pain management and palliative purposes. We also excluded patients with choledocholithiasis, pancreato-biliary malignancies and had cholecystectomy in the past. We collected demographic, laboratory and ultrasound imaging details by accessing our electronic medical records. We divided the patients into two groups based on common bile duct dilatation of more than 6 mm. Data was analyzed using standard statistical methods and JMP 12 software. Results: There were a total of 176 patients who met inclusion criteria. There was no difference in ethnicity and age between the two groups (Table 1). We also did not notice any difference in mean methadone dosage between the two groups. However, we observed more females (50 % vs 36% p 0.04) in the group with biliary dilatation compared to group without biliary dilatation. We also observed that mean CBD diameter in females is more than their male counter parts (6.8 mm vs. 5.8 mm, p 0.03)Table 1Conclusion: Methadone has been known to be associated with non-pathological biliary dilatation. Our study concluded that female gender is more commonly associated with biliary dilatation in individuals on MMT. We also conclude that mean biliary diameter is higher in females compared to males. Even though common physiological pathway can lead to non-pathological dilatation of biliary tract in patients on MMT, females are more likely to have biliary dilatation. Further research at molecular level can track the physiological phenomenon leading to these changes.

Immunocytochemistry for Claudin-18 and Maspin in biliary brushing cytology increases the accuracy of diagnosing pancreatobiliary malignancies.

Biliary brush cytology is an important diagnostic tool in the evaluation of pancreatobiliary malignancies. However, it is difficult to distinguish between malignant and benign cells. The present study evaluated the utility of immunocytochemical expression of Claudin-18 and Maspin in brushing cytology specimens of pancreatobiliary lesions in the diagnosis of pancreatobiliary malignancies. The study retrospectively assessed biliary and pancreatic duct brushing cytology specimens of 43 patients whose pancreatobiliary lesions were histologically diagnosed at the University of Miyazaki Hospital. Scanty cellularity slides and cases with no histological confirmation were excluded. Alcohol-fixed and Papanicolaou-stained slides were immunostained with monoclonal antibodies to Claudin-18 and Maspin. Of the 43 patients, 35 (81.4%) were finally histologically diagnosed with invasive adenocarcinomas. The sensitivity of routine cytology for the detection of malignancy was 63%, and the specificity was 100%. The sensitivity of cytology in combination with immunocytochemical expression of Claudin-18 (89%) or Claudin-18 and/or Maspin (97%) was significantly higher than that of cytology alone (P < 0.01). Immunocytochemical staining for Claudin-18 and Maspin improved the diagnostic sensitivity for pancreatobiliary adenocarcinomas.

PTH-011 Novel Endoscopic Ultrasound-Guided Interventional Techniques for The Palliative Management of Malignant Biliary Tract Obstruction: A Single UK Centre Experience

Introduction Endoscopic retrograde cholangiopancreatography (ERCP) is used as the first-line modality for biliary drainage in patients with obstructive jaundice. However, anatomical or technical factors may preclude conventional trans-papillary biliary access in less than 10% of cases. Endoscopic ultrasound-guided biliary drainage (EUS-BD) has recently emerged as an alternative method to percutaneous transhepatic biliary drainage (PTBD) or surgical biliary bypass after unsuccessful ERCP in patients with inoperable pancreatobiliary malignancies. We present initial experience of EUS-BD in our unit. Methods A prospectively collected database, of consecutive patients undergoing EUS-BD in our unit, was analysed. Data was retrieved from electronic, clinical and endoscopy records. All EUS-BD procedures were undertaken in the endoscopy department, under conscious sedation, using Pentax echoendoscopes and Hitachi ultrasound workstations. In all cases, conventional diagnostic EUS procedure was performed followed by trans-luminal EUS-guided placement of metal stents. One of three endoscopists (KO/MN/MD) performed the procedures. The primary outcome measurements were technical success, clinical success and adverse events. Results 4 EUS-BD procedures were performed in 4 patients – ¾ were female (75%) with median age 70 years (range 51–79). The primary indication in all patients was malignant biliary obstruction, which was not amenable to either PTBD or surgery. One patient had symptomatic cystic duct obstruction with gallbladder empyema. 1 patient received a Hot AXIOS™ covered lumen apposing metal stent (cLAMS), 1 had a Wallflex™ biliary fully covered self-expanding metal stent (fcSEMS) and the others had NAGI™ covered self-expanding metal stents (cSEMS) inserted. Technical and clinical success was 100% across all procedures with symptomatic improvement noted in all patients. Serum bilirubin measurements decremented post EUS-BD by median 89% (range 85–98%). No procedure related complications were seen. During follow up, 3/4 patients have died (median 7 months (range 3–8) from date of EUS-BD) of end-stage disease (unrelated to the EUS-BD procedure). The 4th patient remains clinically stable on follow-up (2 months after EUS-BD) with no evidence of further biliary symptoms. Conclusion Our early experience of EUS-BD confirms that it is a safe and effective palliative procedure in patients with malignant biliary tract obstruction, in whom surgery and/or PTBD are less favourable. We recommend that EUS-BD is performed after multidisciplinary team discussion and by experienced therapeutic endosonographers. Disclosure of Interest None Declared

Prospective randomized controlled trial comparing laparoscopic versus open pancreaticoduodenectomy for malignant periampullary and pancreatic head lesions

Background: Current literature supports the use of laparoscopic pancreaticoduodenectomy (LPD) as an alternative to open pancreaticoduodenectomy (OPD) for pancreatobiliary malignancies. Studies done so far are case series and matched comparisons; a randomized trial analysing two has not been reported. Materials and method: Trial included 64 patients with resectable peri-ampullary or pancreatic head cancer, randomized by computer generated random numbers into either LPD or OPD group during September 2013 to August 2015. Sample size was 32 in each arm, assuming power of study 80% & type I error of 0.05. Primary outcome measure was hospital stay, secondary outcome measures were blood loss, operation time, pathological radicality and complication rate. Results: Mean operative time 260.2 min (±11.10) in OPD, 359.4 min (±13.84) in LPD (p = 0.0308). Mean blood loss 300.6 ml (±46.56) in OPD, 249.8 ml (±22.33) in LPD (p<0.001). Conversion rate of 3.1%. The median length of stay in OPD was 12 days (6–30), LPD of 8 days (5–52) (p = 0.0001). Pancreatic fistula 18.75% in OPD; 15.60% in LPD (p = 0.314), overall complications (Clavien Dindo) 31.25% in OPD; 25% in LPD (p = 0.755) and 3.1% mortality in each arm. Mean nodes retrieved in OPD 17.00 (±1.47), LPD 18.97 (±1.0) with 0.95 CI, p = 0.059. Conclusion: This study establishes safety of LPD in terms of short term outcomes, complications, mortality and oncological radicality to that of OPD, has benefits of shorter hospital stay, reduced blood loss and lesser wound complications. Comparisons in terms of disease free survival and long term survival remains to be seen (NCT02081131).