Impact of metal and plastic stents on endoscopic ultrasound-guided aspiration cytology and core histology of head of pancreas masses.

BACKGROUND: Stents are frequently placed in patients with biliary obstruction due to a mass in the head of the pancreas. The impact of plastic or self-expandable metal stents (SEMSs) on endoscopic ultrasound (EUS)-guided tissue sampling is unclear. This study aimed to assess, using strict pathological criteria, whether stents impair fine-needle aspiration (FNA) or fine-needle biopsy (FNB). METHODS: All patients with a solid mass in the head of the pancreas who underwent EUS-guided tissue sampling between 2010 and 2016 at our unit were included. Factors with possible impact on diagnostic performance were analyzed using logistic regression. Analysis was performed using both strict (malignant only) and less strict (suspicious for malignancy) cutoffs. RESULTS: Of 631 individuals undergoing 698 procedures, 535 (84.8 %) had a final diagnosis of malignancy, 141 had SEMS, 149 had plastic stents, and 341 had no stent. Using strict criteria, SEMS were associated with an increased occurrence of incorrect diagnosis of EUS tissue sampling, with an odds ratio (OR) of 1.96 (95 % confidence interval [CI] 1.24 - 3.10). Increasing tumor size (OR 0.72, 95 %CI 0.59 - 0.87), increasing number of passes (OR 0.84, 95 %CI 0.72 - 0.99), and fork-tip biopsy needle (OR 0.52, 95 %CI 0.31 - 0.86) were independently associated with a decrease in incorrect diagnosis. Repeat tissue sampling was more common with SEMSs (10.2 %) than with plastic stents (2.9 %) or no stents (4.5 %) (P < 0.02). CONCLUSION: SEMS use had a negative impact on tissue diagnosis in pancreatic head masses, whereas use of a fork-tip biopsy needle and increasing number of passes were independently associated with improved accuracy.

Diagnosis and management of pancreatic cancer in adults: A summary of guidelines from the UK National Institute for Health and Care Excellence.

To enable standardisation of care of pancreatic cancer patients and facilitate improvement in outcome, the United Kingdom's National Institute for Health and Care Excellence (NICE) developed a clinical guideline for the diagnosis and management of pancreatic cancer in adults. Systematic literature searches, systematic review and meta-analyses were undertaken. Recommendations were drafted on the basis of the group's interpretation of the best available evidence of clinical and cost effectiveness. There was patient involvement and public consultation. Recommendations were made on: diagnosis; staging; monitoring of inherited high risk; psychological support; pain; nutrition management; and the specific management of people with resectable-, borderline-resectable- and unresectable-pancreatic cancer. The guideline committee also made recommendations for future research into neoadjuvant therapy, cachexia interventions, minimally invasive pancreatectomy, pain management and psychological support needs. These NICE guidelines aim to promote best current practice and support and stimulate research and innovation in pancreatic cancer.

Sulfatase-2: a prognostic biomarker and candidate therapeutic target in patients with pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is the fifth most common cause of cancer death in the UK. Its poor prognosis is attributed to late detection and limited therapeutic options. Expression of SULF2, an endosulfatase that modulates heparan sulfate proteoglycan 6-O-sulfation and is reportedly tumourigenic in different types of cancer, was investigated. METHODS: SULF2 expression was determined immunohistochemically in archival surgical resection tissue sections from 93 patients with a confirmed histological diagnosis of PDAC between 2002 and 2008 followed for a median of 9 years. Relationships with clinico-pathological parameters and patient survival were explored. RESULTS: The majority of PDACs showed positive SULF2 staining in tumour cells and intratumoural or tumour-adjacent stroma. Greater than 25% SULF2-positive tumour cells was present in 60% of cancers and correlated with tumour stage (P=0.002) and perineural invasion (P=0.024). SULF2 intensity was scored moderate or strong in 81% of cancers and positively correlated with vascular invasion (P=0.015). High SULF2 expression, defined as >50% SULF2-positive tumour cells and strong SULF2 staining, was associated with shorter time to radiological progression (P=0.018, HR 1.98, CI 1.13-3.47). Similarly, by multivariate analysis, high SULF2 expression was independently associated with poorer survival (P=0.004, HR 2.10, CI 1.26-3.54), with a median survival of 11 months vs 21 months for lower PDAC SULF2. CONCLUSIONS: Elevated SULF2 in PDAC was associated with advanced tumour stage, vascular invasion, shorter interval to radiological progression and shorter overall survival. SULF2 may have roles as a prognostic biomarker and as a therapeutic target for patients with PDAC.

Chronic pancreatitis: Do serum biomarkers provide an association with an inflammageing phenotype?

BACKGROUND: Chronic pancreatitis is an inflammatory disorder of the pancreas that is associated with accelerated mortality for patients suffering from this disease. The association between chronic inflammation and accelerated biological ageing has been well described and is often referred to as "inflammageing". In this review we seek to determine how systemic inflammation in chronic pancreatitis may contribute to an accelerated ageing phenotype. METHODS: A systematic literature search with a predefined search protocol was performed on Medline, Embase and Cochrane libraries according to the PRISMA guidelines. RESULTS: The initial search identified 499 studies. After title, abstract and full text screen of the search results, 20 were included for further evaluation. In the 20 remaining articles 41 inflammatory mediators were identified - mainly involved in chronic inflammation, fibrosis and particularly cardinal features of inflammageing such as sarcopenia and osteoporosis. CONCLUSION: Chronic pancreatitis is associated with elevated levels of inflammatory mediators many of which are associated with an accelerated ageing phenotype and may explain some of the clinical sequelae of this disease.

Endoscopic drainage of walled-off pancreatic necrosis using a novel self-expanding metal stent.

BACKGROUND AND STUDY AIMS: This report describes the use of a novel, fully covered, self-expanding metal stent (FCSEMS) for endoscopic ultrasound (EUS)-guided drainage of walled-off pancreatic necrosis (WON). PATIENTS AND METHODS: Patients with WON, as defined by the revised Atlanta Criteria, were included in this open-lable, two-center, observational study. The WON was punctured using a cystotome, and the FCSEMS was inserted under fluoroscopic guidance. Necrosectomy procedures were performed as necessary. RESULTS: A total of 19 patients were included. The median maximum collection size was 15 cm with a median of 50 % necrosis. A total of 14/19 patients underwent necrosectomy, requiring a median of 4 procedures. Resolution or reduction in the size of collection by at least 80 % was achieved in all patients. Percutaneous or surgical drainage was required in three patients. Five stents migrated or dislodged. One patient had abdominal pain post-procedure. Five patients died during follow-up (three from multi-organ failure, and two unrelated to pancreatitis). CONCLUSIONS: Use of this stent is feasible and safe for drainage of WON. However, stent displacement rates were high, and improvements to the stent design are required before it can be advocated for routine use in WON.

Endoscopic ultrasound in patients with normal liver blood tests and unexplained dilatation of common bile duct and or pancreatic duct.

OBJECTIVE: To determine the yield of endoscopic ultrasound (EUS) in the investigation of patients with normal liver function tests (LFTs) and unexplained dilatation of common bile duct (CBD) and/or pancreatic duct (PD), following CT and/or magnetic resonance cholangiopancreatography. MATERIALS AND METHODS: Consecutive patients undergoing linear EUS between January 2007 and August 2011 for the indication of dilated CBD and/or PD, normal LFT, and nondiagnostic cross-sectional imaging formed the study group. The study was performed as a retrospective analysis of prospectively collected data. RESULTS: During the study period, 83 patients (CBD and PD dilatation n = 38, PD dilatation n = 5, CBD dilatation n = 40) met the inclusion criteria and underwent EUS. Five (13.1%) of the CBD and PD groups had a new finding, which in one (2.6%) case was causal. In this group, men were significantly more likely to have a new finding (p = 0.012). Eight (20%) of the CBD group had a new finding, which in seven (17.5%) cases was causal. In the CBD group, cholecystectomy was significantly (p = 0.005) more common in those without a finding. Three (60%) of the PD group had a finding on EUS, all of which were causal, including a case of pancreatic malignancy. CONCLUSION: There is a significant yield from EUS in individuals with isolated PD dilatation and isolated CBD dilatation. Previous cholecystectomy is significantly associated with a negative EUS in the group with isolated CBD dilatation. The yield in those with CBD and PD dilatation was low and a finding was more likely in males.

Incidental pT2-T3 gallbladder cancer after a cholecystectomy: outcome of staging at 3 months prior to a radical resection.

INTRODUCTION: Patients with incidental pT2-T3 gallbladder cancer (IGC) after a cholecystectomy may benefit from a radical re-resection although their optimal treatment strategy is not well defined. In this Unit, such patients undergo delayed staging at 3 months after a cholecystectomy to assess the evidence of a residual tumour, extra hepatic spread and the biological behaviour of the tumour. The aim of this study was to evaluate the outcome of patients who had delayed staging at 3 months after a cholecystectomy. METHODS: From July 2003 to July 2011, 56 patients with T2-T3 gallbladder cancer were referred to this Unit of which 49 were diagnosed incidentally on histology after a cholecystectomy. All 49 patients underwent delayed pre-operative staging using multi-detector computed tomography (MDCT) followed selectively by laparoscopy at 3 months after a cholecystectomy. Data were collected from a prospectively held database. The peri-operative and long-term outcomes of patients were analysed. SPSS software was used for statistical analysis. RESULTS: There were 38 pT2 and 11 pT3 tumours. After delayed staging, 24/49 (49%) patients underwent a radical resection, 24/49 (49%) were found to be inoperable on pre-operative assessment and 1/49 (2%) patient underwent an exploratory laparotomy and were found to be unresectable. The overall median survival from referral was 20.7 months (54.8 months for the group who had a radical re-resection versus 9.7 months for the group who had unresectable disease, P < 0.001). These results compare favourably with the reported outcome of fast-track management for incidental pT2-T3 gallbladder cancer from other major series in the literature. CONCLUSION: Delayed staging in patients with incidental T2-T3 gallbladder cancer after a cholecystectomy is a useful strategy to select patients who will benefit from a resection and avoid unnecessary major surgery.

N-acetylcysteine administration does not improve patient outcome after liver resection.

BACKGROUND: Post-operative hepatic dysfunction is a major cause of concern when undertaking a liver resection. The generation of reactive oxygen species (ROS) as a result of hepatic ischaemia/reperfusion (I/R) injury can result in hepatocellular injury. Experimental evidence suggests that N-acetylcysteine may ameliorate ROS-mediated liver injury. METHODS: A cohort of 44 patients who had undergone a liver resection and receiving peri-operative N-acetylcysteine (NAC) were compared with a further cohort of 44 patients who did not. Liver function tests were compared on post-operative days 1, 3 and 5. Peri-operative outcome data were retrieved from a prospectively maintained database within our unit. RESULTS: Administration of NAC was associated with a prolonged prothrombin time on the third post-operative day (18.4 versus 16.4 s; P = 0.002). The incidence of grades B and C liver failure was lower in the NAC group although this difference did not reach statistical significance (6.9% versus 14%; P = 0.287). The overall complication rate was similar between groups (32% versus 25%; P = ns). There were two peri-operative deaths in the NAC group and one in the control group (P = NS). CONCLUSION: In spite of promising experimental evidence, this study was not able to demonstrate any advantage in the routine administration of peri-operative NAC in patients undergoing a liver resection.

Clinical characteristics and long-term outcomes following pancreatic injury - An international multicenter cohort study.

Background: Trauma to the pancreas is rare but associated with significant morbidity. Currently available management guidelines are based on low-quality evidence and data on long-term outcomes is lacking. This study aimed to evaluate clinical characteristics and patient-reported long-term outcomes for pancreatic injury. Methods: A retrospective cohort study evaluating treatment for pancreatic injury in 11 centers across 5 European nations over >10 years was performed. Data relating to pancreatic injury and treatment were collected from hospital records. Patients reported quality of life (QoL), changes to employment and new or ongoing therapy due to index injury. Results: In all, 165 patients were included. The majority were male (70.9%), median age was 27 years (range: 6-93) and mechanism of injury predominantly blunt (87.9%). A quarter of cases were treated conservatively; higher injury severity score (ISS) and American Association for the Surgery of Trauma (AAST) pancreatic injury scores increased the likelihood for surgical, endoscopic and/or radiologic intervention. Isolated, blunt pancreatic injury was associated with younger age and pancreatic duct involvement; this cohort appeared to benefit from non-operative management. In the long term (median follow-up 93; range 8-214 months), exocrine and endocrine pancreatic insufficiency were reported by 9.3% of respondents. Long-term analgesic use also affected 9.3% of respondents, with many reported quality of life problems (QoL) potentially attributable to side-effects of opiate therapy. Overall, impaired QoL correlated with higher ISS scores, surgical therapy and opioid analgesia on discharge. Conclusions: Pancreatic trauma is rare but can lead to substantial short- and long-term morbidity. Near complete recovery of QoL indicators and pancreatic function can occur despite significant injury, especially in isolated, blunt pancreatic injury managed conservatively and when early weaning off opiate analgesia is achieved.

Effect of adjuvant chemotherapy with fluorouracil plus folinic acid or gemcitabine vs observation on survival in patients with resected periampullary adenocarcinoma: the ESPAC-3 periampullary cancer randomized trial.

CONTEXT: Patients with periampullary adenocarcinomas undergo the same resectional surgery as that of patients with pancreatic ductal adenocarcinoma. Although adjuvant chemotherapy has been shown to have a survival benefit for pancreatic cancer, there have been no randomized trials for periampullary adenocarcinomas. OBJECTIVE: To determine whether adjuvant chemotherapy (fluorouracil or gemcitabine) provides improved overall survival following resection. DESIGN, SETTING, AND PATIENTS: The European Study Group for Pancreatic Cancer (ESPAC)-3 periampullary trial, an open-label, phase 3, randomized controlled trial (July 2000-May 2008) in 100 centers in Europe, Australia, Japan, and Canada. Of the 428 patients included in the primary analysis, 297 had ampullary, 96 had bile duct, and 35 had other cancers. INTERVENTIONS: One hundred forty-four patients were assigned to the observation group, 143 patients to receive 20 mg/m2 of folinic acid via intravenous bolus injection followed by 425 mg/m2 of fluorouracil via intravenous bolus injection administered 1 to 5 days every 28 days, and 141 patients to receive 1000 mg/m2 of intravenous infusion of gemcitabine once a week for 3 of every 4 weeks for 6 months. MAIN OUTCOME MEASURES: The primary outcome measure was overall survival with chemotherapy vs no chemotherapy; secondary measures were chemotherapy type, toxic effects, progression-free survival, and quality of life. RESULTS: Eighty-eight patients (61%) in the observation group, 83 (58%) in the fluorouracil plus folinic acid group, and 73 (52%) in the gemcitabine group died. In the observation group, the median survival was 35.2 months (95%% CI, 27.2-43.0 months) and was 43.1 (95%, CI, 34.0-56.0) in the 2 chemotherapy groups (hazard ratio, 0.86; (95% CI, 0.66-1.11; χ2 = 1.33; P = .25). After adjusting for independent prognostic variables of age, bile duct cancer, poor tumor differentiation, and positive lymph nodes and after conducting multiple regression analysis, the hazard ratio for chemotherapy compared with observation was 0.75 (95% CI, 0.57-0.98; Wald χ2 = 4.53, P = .03). CONCLUSIONS: Among patients with resected periampullary adenocarcinoma, adjuvant chemotherapy, compared with observation, was not associated with a significant survival benefit in the primary analysis; however, multivariable analysis adjusting for prognostic variables demonstrated a statistically significant survival benefit associated with adjuvant chemotherapy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00058201.

Impact of prior biliary stenting on diagnostic performance of endoscopic ultrasound for mesenteric vascular staging in patients with head of pancreas and periampullary malignancy.

OBJECTIVE: The diagnostic performance of endoscopic ultrasound (EUS) for stratification of head of pancreas and periampullary tumours into resectable, borderline resectable and locally advanced tumours is unclear as is the effect of endobiliary stents. The primary aim of the study was to assess the diagnostic performance of EUS for resectability according to stent status. DESIGN: A retrospective study was performed. All patients presenting with a solid head of pancreas mass who underwent EUS and surgery with curative intent during an 8-year period were included. Factors with possible impact on diagnostic performance of EUS were analysed using logistic regression. RESULTS: Ninety patients met inclusion criteria and formed the study group. A total of 49 (54%) patients had an indwelling biliary stent at the time of EUS, of which 36 were plastic and 13 were self-expanding metal stents (SEMS). Twenty patients underwent venous resection and reconstruction (VRR). Staging was successfully performed in 100% unstented cases, 97% plastic stent and 54% SEMS, p<0.0001. In successfully staged patients, sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) for classification of resectability were 70%, 70%, 70%, 42% and 88%. For vascular involvement (VI), sensitivity, specificity, accuracy, PPV and NPV were 80%, 68%, 69%, 26% and 96%. Increasing tumour size OR 0.53 (95% CI, 0.30 to 0.95) was associated with a decrease in accuracy of VI classification. CONCLUSIONS: EUS has modest diagnostic performance for stratification of staging. Staging was less likely to be completed when a SEMS was in situ. Staging EUS should ideally be performed before endoscopic retrograde cholangiopancreatography and biliary drainage.

Pancreaticobronchial fistula: a complication of acute pancreatitis.

CONTEXT: Pancreaticobronchial fistula is a rare complication of severe pancreatitis. Various diagnostic methods have been described previously. CASE REPORT: The presentation, diagnostic methods, management and 5-year follow-up of a 40-year-old woman with severe gallstone induced pancreatitis complicated by a pancreaticobronchial fistula were reviewed. Diagnosis was made on the endotracheal intubation when amylase rich-fluid was drained via the tube and confirmed by CT scanning. Successful management was achieved by an open pancreatic necrosectomy, during which air bubbles were seen emerging from the pancreatic collection which supported the diagnosis of the fistula. Five-year follow-up did not reveal any complications. CONCLUSIONS: Pancreaticobronchial fistulas have the potential to cause severe respiratory complications and mortality. Awareness of this condition is important in the treatment of complicated cases of pancreatitis.

Surgical adjuncts to laparoscopic distal pancreatectomy.

Abstract Laparoscopic distal pancreatectomy (LDP) has emerged as an alternative approach to traditional open surgery for managing isolated pathology in the body and tail of the pancreas. Experience with this technique to date is limited with only small series reported in the literature. Common difficulties with this operation are related to dissection of the pancreas from the portal vein and management of the pancreatic stump. In this paper we describe our single centre experience to date and describe strategies we have developed which we believe facilitate safe and effective laparoscopic distal pancreatectomy.

The variable phenotype of the p.A16V mutation of cationic trypsinogen (PRSS1) in pancreatitis families.

OBJECTIVE: To characterise the phenotypes associated with the p.A16V mutation of PRSS1. DESIGN: Clinical and epidemiological data were collected for any family in which a p.A16V mutation was identified, either referred directly to the European Registry of Hereditary Pancreatitis and Familial Pancreatic Cancer or via a collaborator. DNA samples were tested for mutations in PRSS1, SPINK1, CFTR and CTRC. PATIENTS: Participants were recruited on the basis of either family history of pancreatitis (acute or chronic) or the results of genetic testing. Families were categorised as having hereditary pancreatitis (HP), idiopathic disease or pancreatitis in a single generation. HP was defined as >or=2 cases in >or=2 generations. Main outcome measures Onset of painful episodes of pancreatitis, death from pancreatic cancer, diagnosis of diabetes mellitus and exocrine pancreatic failure. RESULTS: Ten families with p.A16V mutations were identified (22 affected individuals): six HP families, three with idiopathic disease and one with only a single generation affected. The median age of onset, ignoring non-penetrants, was 10 years (95% CI 5 to 25). There were eight confirmed cases of exocrine failure, four of whom also had diabetes mellitus. There were three pancreatic cancer cases. Two of these were confirmed as p.A16V carriers, only one of whom was affected by pancreatitis. Those with p.A16V pancreatitis were compared to affected individuals with p.R122H, p.N29I and no PRSS1 mutation. No significant differences were proven using logrank or Mann-Whitney U tests. CONCLUSIONS: Penetrance of p.A16V is highly variable and family dependent, suggesting it contributes to multigenic inheritance of a predisposition to pancreatitis.

Novel multidisciplinary hub-and-spoke tertiary service for the management of severe acute pancreatitis.

OBJECTIVE: Severe acute pancreatitis (SAP) is associated with high mortality (15%-30%). Current guidelines recommend these patients are best managed in a multidisciplinary team setting. This study reports experience in the management of SAP within the UK's first reported hub-and-spoke pancreatitis network. DESIGN: All patients with SAP referred to the remote care pancreatitis network between 2015 and 2017 were prospectively entered onto a database by a dedicated pancreatitis specialist nurse. Baseline characteristics, aetiology, intensive care unit (ICU) stay, interventions, complications, mortality and follow-up were analysed. RESULTS: 285 patients admitted with SAP to secondary care hospitals during the study period were discussed with the dedicated pancreatitis specialist nurse and referred to the regional service. 83/285 patients (29%; 37 male) were transferred to the specialist centre mainly for drainage of infected pancreatic fluid collections (PFC) in 95% (n=79) of patients. Among the patients transferred; 29 (35%) patients developed multiorgan failure with an inpatient mortality of 14% (n=12/83). The median follow-up was 18.2 months (IQR=11.25-35.51). Multivariate analysis showed that transferred patients had statistically significant longer overall hospital stay (p<0.001) but less ICU stay (p<0.012). CONCLUSION: This hub-and-spoke model facilitates the management of the majority of patients with SAP in secondary care setting. 29% warranted transfer to our tertiary centre, predominantly for endoscopic drainage of PFCs. An evidence-based approach with a low threshold for transfer to tertiary care centre can result in lower mortality for SAP and fewer days in ICU.

hENT1 Predicts Benefit from Gemcitabine in Pancreatic Cancer but Only with Low CDA mRNA.

Gemcitabine or 5-fluorouracil (5-FU) based treatments can be selected for pancreatic cancer. Equilibrative nucleoside transporter 1 (hENT1) predicts adjuvant gemcitabine treatment benefit over 5-FU. Cytidine deaminase (CDA), inside or outside of the cancer cell, will deaminate gemcitabine, altering transporter affinity. ESPAC-3(v2) was a pancreatic cancer trial comparing adjuvant gemcitabine and 5-FU. Tissue microarray sections underwent in situ hybridization and immunohistochemistry. Analysis of both CDA and hENT1 was possible with 277 patients. The transcript did not correlate with protein levels for either marker. High hENT1 protein was prognostic with gemcitabine; median overall survival was 26.0 v 16.8 months (p = 0.006). Low CDA transcript was prognostic regardless of arm; 24.8 v 21.2 months with gemcitabine (p = 0.02) and 26.4 v 14.6 months with 5-FU (p = 0.02). Patients with low hENT1 protein did better with 5-FU, but only if the CDA transcript was low (median survival of 5-FU v gemcitabine; 29.3 v 18.3 months, compared with 14.2 v 14.6 with high CDA). CDA mRNA is an independent prognostic biomarker. When added to hENT1 protein status, it may also provide treatment-specific predictive information and, within the frame of a personalized treatment strategy, guide to either gemcitabine or 5FU for the individual patient.

EUS-FNA versus biliary brushings and assessment of simultaneous performance in jaundiced patients with suspected malignant obstruction.

CONTEXT: Individuals with suspected malignant biliary obstruction commonly undergo ERCP for drainage and tissue sampling via biliary brushings. EUS with EUS-FNA facilitates staging and potentially more accurate tissue sampling. OBJECTIVE: The aim is to compare the diagnostic performance of EUS-FNA and ERCP with biliary brushings (ERCP-BB) in the diagnosis of pancreatobiliary carcinoma and the utility of combining the two procedures under conscious sedation. DESIGN: Retrospective analysis of a prospectively maintained database. PATIENTS: Thirty-seven patients with suspected malignant obstructive jaundice underwent 39 paired procedures, either combined (n=22) or within a few days (n=17). RESULTS: Using strict cytological criteria the sensitivity of EUS-FNA in the diagnosis of malignancy was 52.9% (95% CI: 35.1-70.2%) versus 29.4% (95% CI: 15.1-47.5%) for ERCP-BB. Combining the two tests improved sensitivity to 64.7% (95% CI: 46.5-80.3%) which was significantly better than ERCP-BB alone (P=0.001) but not EUS-FNA alone (P=0.125). When both procedures were performed under the same conscious sedation, there was a significant difference (P=0.031) between the sensitivity of EUS-FNA (52.6%; 95% CI: 28.9-75.6%) and that of ERCP-BB (21.1%; 95% CI: 6.1-45.6%). When both procedures were performed together the mean±SD in-room time was 79±14 min (range: 45-105 min). Two of the patients (9.1%) had a complication. CONCLUSIONS: In patients undergoing EUS-FNA and ERCP-BB under the same sedation, EUS-FNA was significantly more sensitive in diagnosing malignancy. Combining the results of both tests improved diagnostic accuracy. Combining therapeutic ERCP and EUS-FNA under the same conscious sedation is feasible, with a complication rate similar to that of ERCP alone.

Therapeutic Strategies Toward Lactate Dehydrogenase Within the Tumor Microenvironment of Pancreatic Cancer.

OBJECTIVES: Pancreatic stellate cells (PSCs) play a key metabolic role within the tumor microenvironment (stroma) of pancreatic ductal adenocarcinoma (PDAC), being glycolytic and associated with protumorigenic acidification from excess lactate. This study investigates the clinical significance of glycolytic enzyme lactate dehydrogenase (LDH) and determines efficacy of the novel pan-LDH inhibitor Galloflavin. METHODS: An in vitro Transwell system was adopted for coculture of PSCs and 3 PDAC cell lines (MIA PaCa-2, PANC-1, and BxPC-3). Cells were treated with Galloflavin, and outcomes were analyzed regarding proliferation, apoptosis, lactate production, and glycolytic enzyme protein expression. Immunohistochemical staining for lactate dehydrogenase B (LDHB) was performed on 59 resected PDAC tumors annotated for clinical outcome. RESULTS: Galloflavin reduced PDAC proliferation in monoculture (P < 0.01); however, in co-culture with PSCs, an antiproliferative effect was only evident in PANC-1 (P = 0.001). An apoptotic effect was observed in MIA PaCa-2 and BxPC-3 in coculture (P < 0.05). A reduction in media lactate was observed in coculture (P < 0.01) with PSCs. Immunohistochemistry revealed stromal and tumoral LDHB expression had no impact on survival. CONCLUSIONS: Galloflavin has the potential to neutralize the acidic PDAC microenvironment and thereby reduce tumor invasiveness and metastasis. Patients with lower LDHB expression are more likely to be beneficial responders.