The Impact of Positive Resection Margins on Survival and Recurrence Following Resection and Adjuvant Chemotherapy for Pancreatic Ductal Adenocarcinoma.

OBJECTIVE AND BACKGROUND: Local and distant disease recurrence are frequently observed following pancreatic cancer resection, but an improved understanding of resection margin assessment is required to aid tailored therapies. METHODS: Analyses were carried out to assess the association between clinical characteristics and margin involvement as well as the effects of individual margin involvement on site of recurrence and overall and recurrence-free survival using individual patient data from the European Study Group for Pancreatic Cancer (ESPAC)-3 randomized controlled trial. RESULTS: There were 1151 patients, of whom 505 (43.9%) had an R1 resection. The median and 95% confidence interval (CI) overall survival was 24.9 (22.9-27.2) months for 646 (56.1%) patients with resection margin negative (R0 >1 mm) tumors, 25.4 (21.6-30.4) months for 146 (12.7%) patients with R1<1 mm positive resection margins, and 18.7 (17.2-21.1) months for 359 (31.2%) patients with R1-direct positive margins (P < 0.001). In multivariable analysis, overall R1-direct tumor margins, poor tumor differentiation, positive lymph node status, WHO performance status ≥1, maximum tumor size, and R1-direct posterior resection margin were all independently significantly associated with reduced overall and recurrence-free survival. Competing risks analysis showed that overall R1-direct positive resection margin status, positive lymph node status, WHO performance status 1, and R1-direct positive superior mesenteric/medial margin resection status were all significantly associated with local recurrence. CONCLUSIONS: R1-direct resections were associated with significantly reduced overall and recurrence-free survival following pancreatic cancer resection. Resection margin involvement was also associated with an increased risk for local recurrence.

A systematic review and meta-analysis of metal versus plastic stents for drainage of pancreatic fluid collections: metal stents are advantageous.

BACKGROUND: The use of fully covered metal stents (FCSEMS) and specifically designed lumen apposing metal stents for transmural drainage of pancreatic fluid collections has become widespread. A systematic review published in 2015 did not support the routine use of metal stents for drainage of pancreatic fluid collections. However, recent studies have shown conflicting data; therefore a systematic review and meta-analysis was performed. METHOD: We conducted a database search for original comparative studies between plastic and metal stents. The random effects model was used to calculate pooled risk ratios (RR) with 95% confidence intervals (CI). Outcomes analysed were clinical success, adverse events and requirement of further intervention. RESULTS: The search identified 936 studies, 7 studies with 681 (340 metal, 341 plastic) patients met inclusion criteria and were included in the meta-analysis. Clinical success was achieved in 93.8% versus 86.2% in the metal and plastic groups, respectively, RR 1.08 [95% CI 1.02-1.14]; p = 0.009. Adverse events were reduced for metal stents when compared with plastic (10.2% vs. 25.0%), RR 0.42 [95% CI 0.22-0.81]; p = 0.010. Metal stent usage reduced bleeding (2.8% vs. 7.9%), RR 0.37; [95% CI 0.18-0.75]; p = 0.006. Further intervention was required in 12.4% of patients in the metal stent group versus 26.7% for plastic stents, RR 0.54; [95% CI 0.22-1.29]; p = 0.165. CONCLUSIONS: The use of metal stents for drainage of pancreatic fluid collections is associated with improved clinical success, fewer adverse events and reduced bleeding compared to plastic stents.

Minimally invasive and endoscopic versus open necrosectomy for necrotising pancreatitis: a pooled analysis of individual data for 1980 patients.

OBJECTIVE: Minimally invasive surgical necrosectomy and endoscopic necrosectomy, compared with open necrosectomy, might improve outcomes in necrotising pancreatitis, especially in critically ill patients. Evidence from large comparative studies is lacking. DESIGN: We combined original and newly collected data from 15 published and unpublished patient cohorts (51 hospitals; 8 countries) on pancreatic necrosectomy for necrotising pancreatitis. Death rates were compared in patients undergoing open necrosectomy versus minimally invasive surgical or endoscopic necrosectomy. To adjust for confounding and to study effect modification by clinical severity, we performed two types of analyses: logistic multivariable regression and propensity score matching with stratification according to predicted risk of death at baseline (low: <5%; intermediate: ≥5% to <15%; high: ≥15% to <35%; and very high: ≥35%). RESULTS: Among 1980 patients with necrotising pancreatitis, 1167 underwent open necrosectomy and 813 underwent minimally invasive surgical (n=467) or endoscopic (n=346) necrosectomy. There was a lower risk of death for minimally invasive surgical necrosectomy (OR, 0.53; 95% CI 0.34 to 0.84; p=0.006) and endoscopic necrosectomy (OR, 0.20; 95% CI 0.06 to 0.63; p=0.006). After propensity score matching with risk stratification, minimally invasive surgical necrosectomy remained associated with a lower risk of death than open necrosectomy in the very high-risk group (42/111 vs 59/111; risk ratio, 0.70; 95% CI 0.52 to 0.95; p=0.02). Endoscopic necrosectomy was associated with a lower risk of death than open necrosectomy in the high-risk group (3/40 vs 12/40; risk ratio, 0.27; 95% CI 0.08 to 0.88; p=0.03) and in the very high-risk group (12/57 vs 28/57; risk ratio, 0.43; 95% CI 0.24 to 0.77; p=0.005). CONCLUSION: In high-risk patients with necrotising pancreatitis, minimally invasive surgical and endoscopic necrosectomy are associated with reduced death rates compared with open necrosectomy.

The diagnostic value of Rosemont and Japanese diagnostic criteria for 'indeterminate', 'suggestive', 'possible' and 'early' chronic pancreatitis.

BACKGROUND: Longitudinal data are lacking to support consensus criteria for diagnosing early chronic pancreatitis. METHODS: Retrospective single centre study of the initial evidence for chronic pancreatitis (CP), with reassessment after follow-up (January 2003-November 2016). RESULTS: 807 patients were previously diagnosed with chronic pancreatitis. This diagnosis was rejected in 118 patients: 52 had another pathology altogether, the remaining 66 patients formed the study population. 38 patients with 'normal' imaging were reclassified as chronic abdominal pain syndrome (CAPS), and 28 patients had minimal change features of CP on EUS (MCEUS) but never progressed. Strict application of the Japanese diagnostic criteria would diagnose only two patients with early CP and eleven as possible CP. Patients were more likely to have MCEUS if the EUS was performed within 12 months of an attack of acute pancreatitis. 40 patients with MCEUS were identified, including an additional 12 who progressed to definite CP after a median of 30 (18.75-36.5) months. Those continuing to consume excess alcohol and/or continued smoking were significantly more likely to progress. Those who progressed were more likely to develop pancreatic exocrine insufficiency, require pancreatic surgery and had higher mortality. CONCLUSION: There needs to be more stringent application of the systems used for diagnosing chronic pancreatitis with revision of the current terminology 'indeterminate', 'suggestive', 'possible', and 'early' chronic pancreatitis. All patients with MCEUS features of CP require ongoing clinical follow up of at least 30 months and all patients with these features should be strongly counselled regarding smoking cessation and abstinence from alcohol.

Outcomes From Minimal Access Retroperitoneal and Open Pancreatic Necrosectomy in 394 Patients With Necrotizing Pancreatitis.

OBJECTIVE: To examine the outcomes from minimal access retroperitoneal pancreatic necrosectomy (MARPN) and open pancreatic necrosectomy (OPN) for severe necrotizing pancreatitis in a single center. BACKGROUND: The optimal management of severe pancreatic necrosis is evolving with a few large center single series. METHODS: Between 1997 and 2013, patients with necrotizing pancreatitis at the Liverpool Pancreas Center were reviewed. Outcome measures were retrospectively analyzed by intention to treat. RESULTS: There were 394 patients who had either MARPN (274, 69.5%) or OPN (120, 30.5%). Complications occurred in 174 MARPN patients (63.5%) and 98 (81.7%) OPN patients (P < 0.001). OPN was associated with increased postoperative multiorgan failure [42 (35%) vs 56 (20.4%), P = 0.001] and median (inter-quartile range) Acute Physiology and Chronic Health Evaluation II score 9 (6-11.5) vs 8 (5-11), P < 0.001] with intensive care required less frequently in MARPN patients [40.9% (112) vs 75% (90), P < 0.001]. The mortality rate was 42 (15.3%) in MARPNs and 28 (23.3%) in OPNs (P = 0.064). Both the mortality and the overall complication rates decreased between 1997-2008 and 2008-2013 [49 (23.8%) vs 21 (11.2%) P = 0.001, respectively; and 151 (73.3%) vs 121 (64.4%), P = 0.080, respectively). Increased mortality was independently associated with age (P < 0.001), preoperative intensive care stay (P = 0.014), and multiple organ failure (P < 0.001); operation before 2008 (P < 0.001) and conversion to OPN (P = 0.035). MARPN independently reduced mortality odds risk (odds ratio = 0.27; 95% confidence interval = 0.12-0.57; P < 0.001). CONCLUSIONS: Increasing experience and advances in perioperative care have led to improvement in outcomes. The role of MARPN in reducing complications and deaths within a multimodality approach remains substantial and should be used initially if feasible.

Management and Outcome of 64 Patients with Pancreatic Serous Cystic Neoplasms.

BACKGROUND: The optimal management approach to pancreatic serous cystic neoplasms (SCNs) is still evolving. METHODS: Consecutive patients with SCN managed at the Liverpool Pancreas Cancer Centre between 2000 and 2013 were retrospectively reviewed. RESULTS: There were 64 patients consisting of 39 women (60.9%) and 25 men (39.1%). Forty-seven patients (73.4%) had surgical removal and 17 (26.6%) were observed. The possibility of a non-SCN malignancy was the predominant indication for resection in 27 (57.4%) patients. Postoperative morbidity occurred in 26 (55.3%) patients with 2 (4.3%) deaths. An increased risk of resection was associated with patient's age (p = 0.011), diagnosis before 2009 (p < 0.001), pain (p = 0.043), possibility of cancer (p = 0.009) and a solid SCN component on imaging (p = 0.002). Independent factors associated with resection were a diagnosis before 2009 (p = 0.005) and a solid SCN component (p < 0.001). Independent factors associated with shorter time to surgical resection were persistent pain (p = 0.003) and a solid SCN component (p = 0.007). CONCLUSION: There was a reduction in the proportion of resections with the application of an observe-only policy for asymptomatic patients with more definite features of SCN. Improved criteria are still required in the remainder of patients with uncertain features of SCN in deciding for intervention or surveillance.

Endoscopic ultrasound-guided choledoco-duodenostomy as an alternative to percutaneous trans-hepatic cholangiography.

BACKGROUND: Endoscopic ultrasonography (EUS)-guided choledochoduodenostomy (CDS) is an alternative to percutaneous transhepatic cholangiography (PTC) drainage in patients with an obstructed biliary system where conventional endoscopic retrograde biliary drainage (ERBD) has been unsuccessful. METHODS: Five EUS-CDS procedures were reviewed to assess whether successful decompression was achieved and maintained. RESULTS: There was technical success in each instance with no immediate complications. There was a significant fall in the median bilirubin of 164 mmol/l. The median follow-up was 44 days. In one patient the stent migrated with no adverse outcome. CONCLUSION: EUS-CDS is a viable alternative to PTC with fewer complications and comparable success rates. EUS-CDS may offer a future route for novel therapeutic advances.

Partial pancreatic resection for pancreatic malignancy is associated with sustained pancreatic exocrine failure and reduced quality of life: a prospective study.

OBJECTIVES: Pancreatic resection for cancer may produce pancreatic exocrine insufficiency (PEI), which is poorly understood. This study examined the coefficient of fat absorption (CFA), symptoms, quality of life (QoL) and the accuracy of faecal elastase-1 (FE-1) measurement to predict PEI. METHODS: Forty patients were analysed following resection for pancreatic malignancy. The primary endpoint was PEI diagnosis defined by CFA <93%; secondary endpoints were PEI diagnosis using FE-1 <200 µg/g, body mass index (BMI), and symptom and QoL analysis. Interventions were 3-day stool collection, EORTC QLQ-C30 (version 1) questionnaire and patient's diary, at 6 weeks and 3, 6 and 12 months after surgery. RESULTS: CFA <93% was present in 67% of patients at 6 weeks and in 55% at 12 months. PEI using FE-1 was present in 77 and 83% of patients, respectively. No significant changes between time-points were observed. Sensitivity, specificity, PPV, NPV and accuracy for FE-1 in detecting CFA <93% were 91, 35, 70, 71 and 70%, respectively. CFA and FE-1 levels were uncorrelated. Overall, QoL increased at 6 (p = 0.0212) and 12 (p < 0.0001) months after surgery, mainly driven by physical, role and social functioning, and by appetite. Importantly, however, BMI and symptoms were unaffected by PEI, which suggests a subclinical presentation; such patients had attributes indicating poorer QoL (notably insomnia, p = 0.0012). CONCLUSIONS: PEI was common and sustained following resection and not associated with significant symptoms. These patients had a tendency toward poorer QoL. FE-1 is a poor surrogate for diagnosing impaired fat absorption. Postoperative pancreatic enzyme replacement should be considered more routinely. and IAP.