Borderline resectable pancreatic cancer: a consensus statement by the International Study Group of Pancreatic Surgery (ISGPS).

BACKGROUND: This position statement was developed to expedite a consensus on definition and treatment for borderline resectable pancreatic ductal adenocarcinoma (BRPC) that would have worldwide acceptability. METHODS: An international panel of pancreatic surgeons from well-established, high-volume centers collaborated on a literature review and development of consensus on issues related to borderline resectable pancreatic cancer. RESULTS: The International Study Group of Pancreatic Surgery (ISGPS) supports the National Comprehensive Cancer Network criteria for the definition of BRPC. Current evidence supports operative exploration and resection in the case of involvement of the mesentericoportal venous axis; in addition, a new classification of extrahepatic mesentericoportal venous resections is proposed by the ISGPS. Suspicion of arterial involvement should lead to exploration to confirm the imaging-based findings. Formal arterial resections are not recommended; however, in exceptional circumstances, individual therapeutic approaches may be evaluated under experimental protocols. The ISGPS endorses the recommendations for specimen examination and the definition of an R1 resection (tumor within 1 mm from the margin) used by the British Royal College of Pathologists. Standard preoperative diagnostics for BRPC may include: (1) serum levels of CA19-9, because CA19-9 levels predict survival in large retrospective series; and also (2) the modified Glasgow Prognostic Score and the neutrophil/lymphocyte ratio because of the prognostic relevance of the systemic inflammatory response. Various regimens of neoadjuvant therapy are recommended only in the setting of prospective trials at high-volume centers. CONCLUSION: Current evidence justifies portomesenteric venous resection in patients with BRPC. Basic definitions were identified, that are currently lacking but that are needed to obtain further evidence and improvement for this important patient subgroup. A consensus for each topic is given.

Early surgery versus optimal current step-up practice for chronic pancreatitis (ESCAPE): design and rationale of a randomized trial.

BACKGROUND: In current practice, patients with chronic pancreatitis undergo surgical intervention in a late stage of the disease, when conservative treatment and endoscopic interventions have failed. Recent evidence suggests that surgical intervention early on in the disease benefits patients in terms of better pain control and preservation of pancreatic function. Therefore, we designed a randomized controlled trial to evaluate the benefits, risks and costs of early surgical intervention compared to the current stepwise practice for chronic pancreatitis. METHODS/DESIGN: The ESCAPE trial is a randomized controlled, parallel, superiority multicenter trial. Patients with chronic pancreatitis, a dilated pancreatic duct (≥5 mm) and moderate pain and/or frequent flare-ups will be registered and followed monthly as potential candidates for the trial. When a registered patient meets the randomization criteria (i.e. need for opioid analgesics) the patient will be randomized to either early surgical intervention (group A) or optimal current step-up practice (group B). An expert panel of chronic pancreatitis specialists will oversee the assessment of eligibility and ensure that allocation to either treatment arm is possible. Patients in group A will undergo pancreaticojejunostomy or a Frey-procedure in case of an enlarged pancreatic head (≥4 cm). Patients in group B will undergo a step-up practice of optimal medical treatment, if needed followed by endoscopic interventions, and if needed followed by surgery, according to predefined criteria. Primary outcome is pain assessed with the Izbicki pain score during a follow-up of 18 months. Secondary outcomes include complications, mortality, total direct and indirect costs, quality of life, pancreatic insufficiency, alternative pain scales, length of hospital admission, number of interventions and pancreatitis flare-ups. For the sample size calculation we defined a minimal clinically relevant difference in the primary endpoint as a difference of at least 15 points on the Izbicki pain score during follow-up. To detect this difference a total of 88 patients will be randomized (alpha 0.05, power 90%, drop-out 10%). DISCUSSION: The ESCAPE trial will investigate whether early surgery in chronic pancreatitis is beneficial in terms of pain relief, pancreatic function and quality of life, compared with current step-up practice. TRIAL REGISTRATION: ISRCTN: ISRCTN45877994.

Locally advanced pancreatic cancer treated with radiation and 5-fluorouracil: a first step to neoadjuvant treatment?

AIM OF THE STUDY: In two institutions, a retrospective analysis was performed on patients with histologically proven locally advanced pancreatic cancer without distant metastases. The aim of this analysis is to assess whether chemoradiotherapy provides survival benefit for patients with locally advanced pancreatic cancer. METHODS: Forty-five patients from the Erasmus Medical Centre (Erasmus MC), Rotterdam, received 5-fluorouracil (5-FU) and radiotherapy and, 38 patients from the Academic Medical Centre Amsterdam (AMC) were offered the best supportive care. Radiotherapy consisted of 50 Gy external upper abdomen radiation in two courses, concomitant with intravenous 5-FU 25 mg/kg/ 24 h continuously on the first 4 days of each treatment course. RESULTS: The treatment protocol was completed in 38 of 45 patients (84%) without complications. Radiological response was evaluated in 38 patients. Ten patients (26%) showed a partial response, stable disease was seen in 6 (16%) patients and progressive disease in 22 (58%) patients. A second-look operation was performed in 8 of 10 patients (72%) showing a radiological response, in 3 patients the tumour could be resected. Median overall survival time for the Erasmus MC group (n = 45) was 9.8 months compared to 7.6 months when the best supportive care was given (AMC group, p = 0.04). CONCLUSION: Although overall survival remains poor, treatment with 5-FU and radiotherapy might benefit some patients with locally advanced pancreatic cancer.