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.

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.

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.

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.

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.

Systemic inflammation contributes to impairment of quality of life in chronic pancreatitis.

Chronic pancreatitis (CP) is a fibrotic disorder of the pancreas leading to clinical sequelae like pain and an excess of comorbidity including cardiovascular disease and cancers. The aim of this study was to determine the relationship between systemic inflammation and quality of life in patients with CP. Patients were prospectively recruited and underwent a quality of life assessment (EORTC QLQ-C30 and PAN 28). The serum inflammatory profile was assessed using an MSD 30-plex array. The relationship between clinical variables, inflammatory cytokines and quality of life was determined by a GLM-MANOVA and the individual impact of significant variables evaluated by a second ANOVA. In total, 211 patients with a median age of 53 years were recruited across 5 European centres. Gender, age, nicotine and alcohol abuse were clinical variables associated with altered quality of life. Systemic inflammation with high levels of pro-inflammatory cytokines (Eotaxin, IL-1ß, IL-7, IL-8, IL-12/IL-23p40, IL-12p70, IL-13, IL-16, IP-10, MCP-1, MCP-4, MDC, MIP-1a, TARC, TNFß) was associated with diminished quality of life in general and specific domains including pain, physical and cognitive functioning. As conclusion, CP is associated with a systemic inflammatory response that has a negative impact on quality of life and accelerates aging.

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.

Nutritional support and therapy in pancreatic surgery: A position paper of the International Study Group on Pancreatic Surgery (ISGPS).

BACKGROUND: The optimal nutritional therapy in the field of pancreatic surgery is still debated. METHODS: An international panel of recognized pancreatic surgeons and pancreatologists decided that the topic of nutritional support was of importance in pancreatic surgery. Thus, they reviewed the best contemporary literature and worked to develop a position paper to provide evidence supporting the integration of appropriate nutritional support into the overall management of patients undergoing pancreatic resection. Strength of recommendation and quality of evidence were based on the approach of the grading of recommendations assessment, development and evaluation Working Group. RESULTS: The measurement of nutritional status should be part of routine preoperative assessment because malnutrition is a recognized risk factor for surgery-related complications. In addition to patient's weight loss and body mass index, measurement of sarcopenia and sarcopenic obesity should be considered in the preoperative evaluation because they are strong predictors of poor short-term and long-term outcomes. The available data do not show any definitive nutritional advantages for one specific type of gastrointestinal reconstruction technique after pancreatoduodenectomy over the others. Postoperative early resumption of oral intake is safe and should be encouraged within enhanced recovery protocols, but in the case of severe postoperative complications or poor tolerance of oral food after the operation, supplementary artificial nutrition should be started at once. At present, there is not enough evidence to show the benefit of avoiding oral intake in clinically stable patients who are complicated by a clinically irrelevant postoperative pancreatic fistula (a so-called biochemical leak), while special caution should be given to feeding patients with clinically relevant postoperative pancreatic fistula orally. When an artificial nutritional support is needed, enteral nutrition is preferred whenever possible over parenteral nutrition. After the operation, regardless of the type of pancreatic resection or technique of reconstruction, patients should be monitored carefully to assess for the presence of endocrine and exocrine pancreatic insufficiency. Although fecal elastase-1 is the most readily available clinical test for detection of pancreatic exocrine insufficiency, its sensitivity and specificity are low. Pancreatic enzyme replacement therapy should be initiated routinely after pancreatoduodenectomy and in patients with locally advanced disease and continued for at least 6 months after surgery, because untreated pancreatic exocrine insufficiency may result in severe nutritional derangement. CONCLUSION: The importance of this position paper is the consensus reached on the topic. Concentrating on nutritional support and therapy is of utmost value in pancreatic surgery for both short- and long-term outcomes.

PET-PANC: multicentre prospective diagnostic accuracy and health economic analysis study of the impact of combined modality 18fluorine-2-fluoro-2-deoxy-d-glucose positron emission tomography with computed tomography scanning in the diagnosis and management of pancreatic cancer.

BACKGROUND: Pancreatic cancer diagnosis and staging can be difficult in 10-20% of patients. Positron emission tomography (PET)/computed tomography (CT) adds precise anatomical localisation to functional data. The use of PET/CT may add further value to the diagnosis and staging of pancreatic cancer. OBJECTIVE: To determine the incremental diagnostic accuracy and impact of PET/CT in addition to standard diagnostic work-up in patients with suspected pancreatic cancer. DESIGN: A multicentre prospective diagnostic accuracy and clinical value study of PET/CT in suspected pancreatic malignancy. PARTICIPANTS: Patients with suspected pancreatic malignancy. INTERVENTIONS: All patients to undergo PET/CT following standard diagnostic work-up. MAIN OUTCOME MEASURES: The primary outcome was the incremental diagnostic value of PET/CT in addition to standard diagnostic work-up with multidetector computed tomography (MDCT). Secondary outcomes were (1) changes in patients' diagnosis, staging and management as a result of PET/CT; (2) changes in the costs and effectiveness of patient management as a result of PET/CT; (3) the incremental diagnostic value of PET/CT in chronic pancreatitis; (4) the identification of groups of patients who would benefit most from PET/CT; and (5) the incremental diagnostic value of PET/CT in other pancreatic tumours. RESULTS: Between 2011 and 2013, 589 patients with suspected pancreatic cancer underwent MDCT and PET/CT, with 550 patients having complete data and in-range PET/CT. Sensitivity and specificity for the diagnosis of pancreatic cancer were 88.5% and 70.6%, respectively, for MDCT and 92.7% and 75.8%, respectively, for PET/CT. The maximum standardised uptake value (SUVmax.) for a pancreatic cancer diagnosis was 7.5. PET/CT demonstrated a significant improvement in relative sensitivity (p = 0.01) and specificity (p = 0.023) compared with MDCT. Incremental likelihood ratios demonstrated that PET/CT significantly improved diagnostic accuracy in all scenarios (p < 0.0002). PET/CT correctly changed the staging of pancreatic cancer in 56 patients (p = 0.001). PET/CT influenced management in 250 (45%) patients. PET/CT stopped resection in 58 (20%) patients who were due to have surgery. The benefit of PET/CT was limited in patients with chronic pancreatitis or other pancreatic tumours. PET/CT was associated with a gain in quality-adjusted life-years of 0.0157 (95% confidence interval -0.0101 to 0.0430). In the base-case model PET/CT was seen to dominate MDCT alone and is thus highly likely to be cost-effective for the UK NHS. PET/CT was seen to be most cost-effective for the subgroup of patients with suspected pancreatic cancer who were thought to be resectable. CONCLUSION: PET/CT provided a significant incremental diagnostic benefit in the diagnosis of pancreatic cancer and significantly influenced the staging and management of patients. PET/CT had limited utility in chronic pancreatitis and other pancreatic tumours. PET/CT is likely to be cost-effective at current reimbursement rates for PET/CT to the UK NHS. This was not a randomised controlled trial and therefore we do not have any information from patients who would have undergone MDCT only for comparison. In addition, there were issues in estimating costs for PET/CT. Future work should evaluate the role of PET/CT in intraductal papillary mucinous neoplasm and prognosis and response to therapy in patients with pancreatic cancer. STUDY REGISTRATION: Current Controlled Trials ISRCTN73852054 and UKCRN 8166. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

A comparison of outcomes between a lumen-apposing metal stent with electrocautery-enhanced delivery system and a bi-flanged metal stent for drainage of walled-off pancreatic necrosis.

BACKGROUND AND STUDY AIMS: Bi-flanged metal stents (BFMS) have shown promise in the drainage of walled-off pancreatic necrosis (WON), but their placement requires multiple steps and the use of other devices. More recently, a novel device consisting of a combined lumen-apposing metal stent (LAMS) and electrocautery-enhanced delivery system has been introduced. The aim of this study was to compare the placement and outcomes of the two devices. PATIENTS AND METHODS: This was a retrospective review of consecutive patients undergoing endoscopic ultrasound-guided placement of BFMS or LAMS for drainage of symptomatic WON. Data from procedures between October 2012 and December 2016 were taken from a prospectively maintained database. We compared technical and clinical success, procedure time, costs, and composite end point of significant events (adverse events, stent migration, additional percutaneous drainage) between BFMS and LAMS. RESULTS: 72 consecutive patients underwent placement of BFMS (40 patients, 44 stents) or LAMS (32 patients, 33 stents). Technical success was 91 % for BFMS and 97 % for LAMS. Clinical success was 65 % vs. 78 %, respectively. Median in-room procedure time was significantly shorter in the LAMS group (45 minutes [range 30 - 80]) than in the BFMS group (62.5 minutes [range 35 - 135]; P  < 0.001) and fewer direct endoscopic necrosectomies (DEN) were performed (median 1 [0 - 2.0] vs. 2 [0 - 3.7], respectively; P  = 0.005). If only inpatients were considered (35 BFMS and 19 LAMS), there was no significant difference in DEN 2 (range 0 - 11) and 2 (range 0 - 8), respectively. The composite end point of 32 % vs. 24 % was not significantly different. Median procedural costs for all patients with successful stent placement for WON treatment was €4427 (range 1630 - 12 926) for BFMS vs. €3500 (range 2509 - 13 393) for LAMS ( P  = 0.10). CONCLUSION: LAMS was superior to BFMS in terms of procedure time, with comparable adverse events, success, and costs.

Describing Peripancreatic Collections According to the Revised Atlanta Classification of Acute Pancreatitis: An International Interobserver Agreement Study.

OBJECTIVES: Severe acute pancreatitis is associated with peripancreatic morphologic changes as seen on imaging. Uniform communication regarding these morphologic findings is crucial for accurate diagnosis and treatment. For the original 1992 Atlanta classification, interobserver agreement is poor. We hypothesized that for the revised Atlanta classification, interobserver agreement will be better. METHODS: An international, interobserver agreement study was performed among expert and nonexpert radiologists (n = 14), surgeons (n = 15), and gastroenterologists (n = 8). Representative computed tomographies of all stages of acute pancreatitis were selected from 55 patients and were assessed according to the revised Atlanta classification. The interobserver agreement was calculated among all reviewers and subgroups, that is, expert and nonexpert reviewers; interobserver agreement was defined as poor (≤0.20), fair (0.21-0.40), moderate (0.41-0.60), good (0.61-0.80), or very good (0.81-1.00). RESULTS: Interobserver agreement among all reviewers was good (0.75 [standard deviation, 0.21]) for describing the type of acute pancreatitis and good (0.62 [standard deviation, 0.19]) for the type of peripancreatic collection. Expert radiologists showed the best and nonexpert clinicians the lowest interobserver agreement. CONCLUSIONS: Interobserver agreement was good for the revised Atlanta classification, supporting the importance for widespread adaption of this revised classification for clinical and research communications.

Pancreatic anastomosis after pancreatoduodenectomy: A position statement by the International Study Group of Pancreatic Surgery (ISGPS).

BACKGROUND: Clinically relevant postoperative pancreatic fistula (grades B and C of the ISGPS definition) remains the most troublesome complication after pancreatoduodenectomy. The approach to management of the pancreatic remnant via some form of pancreatico-enteric anastomosis determines the incidence and severity of clinically relevant postoperative pancreatic fistula. Despite numerous trials comparing diverse pancreatico-enteric anastomosis techniques and other adjunctive strategies (pancreatic duct stenting, somatostatin analogues, etc), currently, there is no clear consensus regarding the ideal method of pancreatico-enteric anastomosis. METHODS: An international panel of pancreatic surgeons working in well-known, high-volume centers reviewed the best contemporary literature concerning pancreatico-enteric anastomosis and worked to develop a position statement on pancreatic anastomosis after pancreatoduodenectomy. RESULTS: There is inherent risk assumed by creating a pancreatico-enteric anastomosis based on factors related to the gland (eg, parenchymal texture, disease pathology). None of the technical variations of pancreaticojejunal or pancreaticogastric anastomosis, such as duct-mucosa, invagination method, and binding technique, have been found to be consistently superior to another. Randomized trials and meta-analyses comparing pancreaticogastrostomy versus pancreaticojejunostomy yield conflicting results and are inherently prone to bias due to marked heterogeneity in the studies. The benefit of stenting the pancreatico-enteric anastomosis to decrease clinically relevant postoperative pancreatic fistula is not supported by high-level evidence. While controversial, somatostatin analogues appear to decrease perioperative complications but not mortality, although consistent data across the more than 20 studies addressing this topic are lacking. The Fistula Risk Score is useful for predicting postoperative pancreatic fistula as well as for comparing outcomes of pancreatico-enteric anastomosis across studies. CONCLUSION: Currently, no specific technique can eliminate development of clinically relevant postoperative pancreatic fistula. While consistent practice of any standardized technique may decrease the rate of clinically relevant postoperative pancreatic fistula, experienced surgeons can have lower postoperative pancreatic fistula rates performing a variety of techniques depending on the clinical situation. There is no clear evidence on the benefit of internal or external stenting after pancreatico-enteric anastomosis. The use of somatostatin analogues may be important in decreasing morbidity after pancreatoduodenectomy, but it remains controversial. Future studies should focus on novel approaches to decrease the rate of clinically relevant postoperative pancreatic fistula with appropriate risk adjustment.

Definition and classification of chyle leak after pancreatic operation: A consensus statement by the International Study Group on Pancreatic Surgery.

BACKGROUND: Recent literature suggests that chyle leak may complicate up to 10% of pancreatic resections. Treatment depends on its severity, which may include chylous ascites. No international consensus definition or grading system of chyle leak currently is available. METHODS: The International Study Group on Pancreatic Surgery, an international panel of pancreatic surgeons working in well-known, high-volume centers, reviewed the literature and worked together to establish a consensus on the definition and classification of chyle leak after pancreatic operation. RESULTS: Chyle leak was defined as output of milky-colored fluid from a drain, drain site, or wound on or after postoperative day 3, with a triglyceride content ≥110 mg/dL (≥1.2 mmol/L). Three different grades of severity were defined according to the management needed: grade A, no specific intervention other than oral dietary restrictions; grade B, prolongation of hospital stay, nasoenteral nutrition with dietary restriction, total parenteral nutrition, octreotide, maintenance of surgical drains, or placement of new percutaneous drains; and grade C, need for other more invasive in-hospital treatment, intensive care unit admission, or mortality. CONCLUSION: This classification and grading system for chyle leak after pancreatic resection allows for comparison of outcomes between series. As with the other the International Study Group on Pancreatic Surgery consensus statements, this classification should facilitate communication and evaluation of different approaches to the prevention and treatment of this complication.

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.

The role of exosomes in the pathogenesis of pancreatic ductal adenocarcinoma.

Exosomes are small membrane bound vesicles secreted by cancer cells that have a cytosol rich in proteins and nucleic acids which are capable of modulating the phenotype of neighbouring cells which take them up. In this review we explore the mechanisms through which exosomes are able to impact on the pathogenesis of pancreatic ductal cancer through the modulation of tumour formation and development and exploitation of the tumour microenvironment to modulate both the adaptive and innate immune response. In addition we highlight the potential utility of exosomes not only as biomarkers of disease but also as tools to be used in the therapeutic armamentarium against this disease.