Review article: enzyme supplementation in cystic fibrosis, chronic pancreatitis, pancreatic and periampullary cancer

Background: Over 11 000 UK patients each year develop pancreatic exocrine insufficiency - the major causes are not rare: cystic fibrosis (&gt;300 new cases/year), pancreatic cancer (&gt;7000 new cases/year) and chronic pancreatitis (&gt;4000 new cases/year). Affected patients present in diverse ways, and for chronic pancreatitis, diagnosis is frequently made rather late in the course of the disease. Aim: To raise awareness of key clinical issues specific to patients with pancreatic exocrine insufficiency through experience from UK clinicians, and to offer advice regarding appropriate treatment with pancreatic enzymes. Methods: Three case studies describe clinical issues relating to pancreatic enzyme supplementation that may lead to underuse in patients with cystic fibrosis, pancreatic and periampullary cancer or chronic pancreatitis. Results: The efficacy of the treatment of exocrine pancreatic insufficiency is dependent on adequate meal:time enzyme replacement therapy. Improvements in patients' weight and nutritional status are what is aimed for - an important reason for all doctors, nurses and dieticians to give this therapy close attention. Conclusions: Pancreatic exocrine insufficiency may result in malnutrition, but enzyme supplementation can greatly improve quality of life in these patients.</p

Evaluation of an inflammation-based prognostic score in patients with inoperable pancreatic cancer

Background/Aims: Patients with pancreatic cancer have one of the poorest survival rates and selection of patients for active treatment remains problematical. The present study assesses the value of an inflammation-based score (Glasgow Prognostic Score, GPS) in patients with inoperable pancreatic cancer. Methods: The GPS was constructed as follows: patients with both an elevated C-reactive protein (&#62;10 mg/l) and hypoalbuminaemia (&#60;35 g/l) were allocated a score of 2. Patients in whom only 1 or none of these biochemical abnormalities was present were allocated a score of 1 or 0, respectively. Results: One hundred and eighty-seven patients were studied and 49 (26%) underwent an operative palliative bypass procedure. At the end of follow-up, 181 (97%) patients died, 17% of patients were alive at 12 months. On univariate analysis, age (p &#60; 0.01), TNM stage (p &#60; 0.001) and the GPS (p &#60; 0.001) were significant predictors of survival. On multivariate survival analysis, stratified for bypass procedure, age (hazard ratio 1.53, 95%CI 1.12–2.10, p = 0.008), TNM stage (hazard ratio 1.70, 95%CI 1.33–2.18, p &#60; 0.001) and the GPS (hazard ratio 1.72, 95%CI 1.40–2.11, p &#60; 0.001) remained independent significant predictors of survival. Conclusion: At diagnosis, the presence of a systemic inflammatory response (as measured by the GPS) appears to be a useful indicator of poor outcome, independent of TNM stage, in patients with inoperable pancreatic cancer

Peripancreatic Fat Invasion Is an Independent Predictor of Poor Outcome Following Pancreaticoduodenectomy for Pancreatic Ductal Adenocarcinoma

Background Following pancreaticoduodenectomy for pancreatic ductal adenocarcinoma (PDAC), identification of peripancreatic fat tumor invasion promotes a tumor to stage T3. We sought to understand better the impact of histological peripancreatic fat invasion on prognosis and site of recurrence in a cohort of patients with PDAC. Methods We analyzed the patient demographics, outcome, and recurrence data that had been prospectively collected in 189 consecutive PDAC undergoing potentially curative pancreaticoduodenectomy between 1996 and 2009. Pathological features were reassessed for all patients. Survival outcome was compared using Kaplan-Meier/Cox proportional hazards analysis. The primary site of recurrence was defined as either locoregional or distant metastases. Results The median survival of this PDAC cohort was 18.9 months (95% confidence interval (CI) 15.7-22.2). Histological peripancreatic fat invasion was evident in 51 (27%) patients and was associated with lymph node metastases (p=0.004) and larger tumor size (p=0.015). The presence of peripancreatic fat invasion was associated with reduced overall survival following resection (12.4 months [95% CI 9.9-15.0]) when compared to those patients with no evidence of fat invasion (22.6 months [95% CI 18.5-26.7]; p &lt; 0.0001). By multivariate survival analysis, independent predictors of overall survival included tumor grade (p=0.002), lymph node involvement (p=0.025), resection margin status (p=0.003), venous invasion (p=0.045), and peripancreatic fat invasion (p=0.007). Invasion into the pancreatic fat was significantly associated with the primary site of recurrence being locoregional failure (p=0.002). Conclusions Peripancreatic fat invasion was identified as being an independent predictor of poor outcome following pancreaticoduodenectomy for PDAC. Additionally, the presence of peripancreatic fat invasion was associated with locoregional disease as the primary site of recurrence. This may have implications for the staging of PDAC and potentially require incorporation into future staging systems to improve outcome stratification