Pancreatic exocrine insufficiency following pancreatoduodenectomy: A prospective bi-center study.

BACKGROUND/OBJECTIVES: Pancreatic exocrine insufficiency (PEI) is a common complication following pancreatoduodenectomy (PD) leading to malnutrition. The course of PEI and related symptoms and vitamin deficiencies is unknown. This study aimed to assess the (long-term) incidence of PEI and vitamin deficiencies after PD. METHODS: A bi-centre prospective observational cohort study was performed, including patients who underwent PD for mainly pancreatic and periampullary (pre)malignancies (2014-2018). Two cohorts were formed to evaluate short and long-term results. Patients were followed for 18 months and clinical symptoms were evaluated by questionnaire. PEI was based on faecal elastase-1 (FE-1) levels and/or clinical symptoms. RESULTS: In total, 95 patients were included. After three months, all but three patients had developed PEI and 27/29 (93%) patients of whom stool samples were available showed abnormal FE-1 levels, which did not improve during follow-up. After six months, all patients had developed PEI. During follow-up, symptoms resolved in 35%-70% of patients. Vitamin D and K deficiencies were observed in 48%-79% of patients, depending on the moment of follow-up; 0%-50% of the patients with deficiencies received vitamin supplementation. DISCUSSION: This prospective study found a high incidence of PEI after PD with persisting symptoms in one-to two thirds of all patients. Limited attention was paid to vitamin deficiencies. Improved screening and treatment strategies for PEI and vitamins need to be designed.

Radiofrequency ablation and chemotherapy versus chemotherapy alone for locally advanced pancreatic cancer (PELICAN): study protocol for a randomized controlled trial.

BACKGROUND: Approximately 80% of patients with locally advanced pancreatic cancer (LAPC) are treated with chemotherapy, of whom approximately 10% undergo a resection. Cohort studies investigating local tumor ablation with radiofrequency ablation (RFA) have reported a promising overall survival of 26-34 months when given in a multimodal setting. However, randomized controlled trials (RCTs) investigating the effect of RFA in combination with chemotherapy in patients with LAPC are lacking. METHODS: The "Pancreatic Locally Advanced Unresectable Cancer Ablation" (PELICAN) trial is an international multicenter superiority RCT, initiated by the Dutch Pancreatic Cancer Group (DPCG). All patients with LAPC according to DPCG criteria, who start with FOLFIRINOX or (nab-paclitaxel/)gemcitabine, are screened for eligibility. Restaging is performed after completion of four cycles of FOLFIRINOX or two cycles of (nab-paclitaxel/)gemcitabine (i.e., 2 months of treatment), and the results are assessed within a nationwide online expert panel. Eligible patients with RECIST stable disease or objective response, in whom resection is not feasible, are randomized to RFA followed by chemotherapy or chemotherapy alone. In total, 228 patients will be included in 16 centers in The Netherlands and four other European centers. The primary endpoint is overall survival. Secondary endpoints include progression-free survival, RECIST response, CA 19.9 and CEA response, toxicity, quality of life, pain, costs, and immunomodulatory effects of RFA. DISCUSSION: The PELICAN RCT aims to assess whether the combination of chemotherapy and RFA improves the overall survival when compared to chemotherapy alone, in patients with LAPC with no progression of disease following 2 months of systemic treatment. TRIAL REGISTRATION: Dutch Trial Registry NL4997 . Registered on December 29, 2015. ClinicalTrials.gov NCT03690323 . Retrospectively registered on October 1, 2018.

FOLFIRINOX in Locally Advanced and Metastatic Pancreatic Cancer: A Single Centre Cohort Study.

Introduction: FOLFIRINOX is emerging as new standard of care for fit patients with locally advanced pancreatic cancer (LAPC) and metastatic pancreatic cancer (MPC). However, some of the physicians are reluctant to use FOLFIRINOX due to high toxicity rates reported in earlier studies. We reviewed our experience with FOLFIRINOX in LAPC and MPC, focussing on dose adjustments, toxicity and efficacy. Methods: We reviewed all patients with LAPC or MPC treated with FOLFIRINOX in our institution between April 2011 and December 2015. Unresectability (stage III and IV) was determined by the institution's multidisciplinary team for pancreatic cancer. Results: Fifty patients (18 LAPC and 32 MPC) were enrolled, with a median age of 55 years (IQR 49-66) and WHO performance status of 0/1. FOLFIRINOX was given as first-line treatment in 82% of patients. Dose modifications were applied in 90% of patients. The median number of completed cycles was 8 (IQR 5-9). Grade 3-4 toxicity occurred in 52% and grade 5 toxicity in 2%. The response rate was 25% (12% in LAPC, 32% in MPC). Median overall survival and progression-free survival were 14.8 and 10.3 months in LAPC, and 9.0 and 5.9 months in MPC, respectively. Overall 1- and 2-year survival was 65% and 10% in LAPC and 40% and 5% in MPC. Within the LAPC group, 6 patients (33%) underwent local ablative therapy and 1 patient (6%) a resection, leading to a median survival of 21.8 months. Conclusion: FOLFIRINOX treatment with nearly routine dose modification was associated with acceptable toxicity rates, relatively high response rates and an encouraging overall survival.

Systematic review of innovative ablative therapies for the treatment of locally advanced pancreatic cancer.

BACKGROUND: Locally advanced pancreatic cancer (LAPC) is associated with a very poor prognosis. Current palliative (radio)chemotherapy provides only a marginal survival benefit of 2-3 months. Several innovative local ablative therapies have been explored as new treatment options. This systematic review aims to provide an overview of the clinical outcomes of these ablative therapies. METHODS: A systematic search in PubMed, Embase and the Cochrane Library was performed to identify clinical studies, published before 1 June 2014, involving ablative therapies in LAPC. Outcomes of interest were safety, survival, quality of life and pain. RESULTS: After screening 1037 articles, 38 clinical studies involving 1164 patients with LAPC, treated with ablative therapies, were included. These studies concerned radiofrequency ablation (RFA) (7 studies), irreversible electroporation (IRE) (4), stereotactic body radiation therapy (SBRT) (16), high-intensity focused ultrasound (HIFU) (5), iodine-125 (2), iodine-125-cryosurgery (2), photodynamic therapy (1) and microwave ablation (1). All strategies appeared to be feasible and safe. Outcomes for postoperative, procedure-related morbidity and mortality were reported only for RFA (4-22 and 0-11 per cent respectively), IRE (9-15 and 0-4 per cent) and SBRT (0-25 and 0 per cent). Median survival of up to 25·6, 20·2, 24·0 and 12·6 months was reported for RFA, IRE, SBRT and HIFU respectively. Pain relief was demonstrated for RFA, IRE, SBRT and HIFU. Quality-of-life outcomes were reported only for SBRT, and showed promising results. CONCLUSION: Ablative therapies in patients with LAPC appear to be feasible and safe.