International consensus guidelines for surgery and the timing of intervention in chronic pancreatitis.

BACKGROUND/OBJECTIVES: Chronic pancreatitis (CP) is a complex inflammatory disease with pain as the predominant symptom. Pain relief can be achieved using invasive interventions such as endoscopy and surgery. This paper is part of the international consensus guidelines on CP and presents the consensus guideline for surgery and timing of intervention in CP. METHODS: An international working group with 15 experts on CP surgery from the major pancreas societies (IAP, APA, JPS, and EPC) evaluated 20 statements generated from evidence on 5 questions deemed to be the most clinically relevant in CP. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to evaluate the level of evidence available for each statement. To determine the level of agreement, the working group voted on the 20 statements for strength of agreement, using a nine-point Likert scale in order to calculate Cronbach's alpha reliability coefficient. RESULTS: Strong consensus was obtained for the following statements: Surgery in CP is indicated as treatment of intractable pain and local complications of adjacent organs, and in case of suspicion of malignant (cystic) lesion; Early surgery is favored over surgery in a more advanced stage of disease to achieve optimal long-term pain relief; In patients with an enlarged pancreatic head, a combined drainage and resection procedure, such as the Frey, Beger, and Berne procedure, may be the treatment of choice; Pancreaticoduodenectomy is the most suitable surgical option for patients with groove pancreatitis; The risk of pancreatic carcinoma in patients with CP is too low (2% in 10 year) to recommend active screening or prophylactic surgery; Patients with hereditary CP have such a high risk of pancreatic cancer that prophylactic resection can be considered (lifetime risk of 40-55%). Weak agreement for procedure choice in patients with dilated duct and normal size pancreatic head: both the extended lateral pancreaticojejunostomy and Frey procedure seems to provide equivalent pain control in patients. CONCLUSIONS: This international expert consensus guideline provides evidenced-based statements concerning key aspects in surgery and timing of intervention in CP. It is meant to guide clinical practitioners and surgeons in the treatment of patients with CP.

Identification of Cystic Lesions by Secondary Screening of Familial Pancreatic Cancer (FPC) Kindreds Is Not Associated with the Stratified Risk of Cancer.

OBJECTIVES: Intraductal papillary mucinous neoplasms (IPMNs) are associated with risk of pancreatic ductal adenocarcinoma (PDAC). It is unclear if an IPMN in individuals at high risk of PDAC should be considered as a positive screening result or as an incidental finding. Stratified familial pancreatic cancer (FPC) populations were used to determine if IPMN risk is linked to familial risk of PDAC. METHODS: This is a cohort study of 321 individuals from 258 kindreds suspected of being FPC and undergoing secondary screening for PDAC through the European Registry of Hereditary Pancreatitis and Familial Pancreatic Cancer (EUROPAC). Computerised tomography, endoscopic ultrasound of the pancreas and magnetic resonance imaging were used. The risk of being a carrier of a dominant mutation predisposing to pancreatic cancer was stratified into three even categories (low, medium and high) based on: Mendelian probability, the number of PDAC cases and the number of people at risk in a kindred. RESULTS: There was a median (interquartile range (IQR)) follow-up of 2 (0-5) years and a median (IQR) number of investigations per participant of 4 (2-6). One PDAC, two low-grade neuroendocrine tumours and 41 cystic lesions were identified, including 23 IPMN (22 branch-duct (BD)). The PDAC case occurred in the top 10% of risk, and the BD-IPMN cases were evenly distributed amongst risk categories: low (6/107), medium (10/107) and high (6/107) (P = 0.63). CONCLUSIONS: The risk of finding BD-IPMN was independent of genetic predisposition and so they should be managed according to guidelines for incidental finding of IPMN.

The Liverpool duodenum-and spleen-preserving near-total pancreatectomy can provide long-term pain relief in patients with end-stage chronic pancreatitis.

PURPOSE: Total pancreatectomy may improve symptoms in patients with severe end-stage chronic pancreatitis. This might be achieved whilst preserving both the duodenum- and spleen-(DPSPTP). Mature clinical outcomes of this approach are presented. METHODS: Single-centre prospective cohort study performed between September 1996 and May 2016. Demographic, clinical details, pain scores and employment status were prospectively recorded during clinic attendance. RESULTS: Fifty-one patients (33 men, 18 women) with a median (interquartile range) age of 40.8 (35.3-49.4) years, a median weight of 69.8 (61.0-81.5) Kg and a median body mass index of 23.8 (21.5-27.8), underwent intended duodenum-and spleen-preserving near-total pancreatectomy for end-stage chronic pancreatitis. Aetiology was excess alcohol in 25, idiopathic (no mutation) in 15, idiopathic (SPINK-1/CFTR mutations) in two, hereditary (PRSS1 mutation) in seven and one each post-necrotising pancreatitis and obstructive pancreatic duct divisum in 1. The main indication for surgery was severe pain. Findings included parenchymal calcification in 79% and ductal calculi in 24%, a dilated main pancreatic duct in 57% and a dilated main bile duct in 17%, major vascular involvement in 27% and pancreato-peritoneal fistula in 2%. Postoperative complications occurred in 20 patients with two deaths. Median pain scores were 8 (7-8) preoperatively and 3 (0.25-5.75) at 5 years (p = 0.013). Opiate analgesic use was significantly reduced postoperatively (p = 0.048). Following surgery, 22 (63%) of 38 patients of working age re-entered employment compared with 12 (33%) working preoperatively (p = 0.016). CONCLUSION: Duodenum-and spleen-preserving near-total pancreatectomy provided long-term relief in adult patients with intractable chronic pancreatitis pain, with improved employment prospects.

Endoscopic excision of synchronous large bowel polyps in the presence of colorectal carcinoma: is the fear of malignant cell implantation justified? A systematic review of the literature.

AIM: A systematic review of the literature was performed to establish evidence to support the practice that in the presence of a colonoscopically diagnosed colorectal cancer immediate endoscopic excision of synchronous polyps should not be performed due to the risk of malignant cell implantation at the polypectomy site. METHOD: A systematic literature search was performed using Medline, Embase and the Cochrane Central Register of Controlled Trials to identify studies comparing the rate of implantation of colorectal cancer cells in normal and damaged colonic mucosa and reports of colorectal cancer cells seeding into sites of damaged mucosa after polypectomy. RESULTS: No randomized controlled trials were identified. Three studies involving mammalian models of colonic mucosal damage were included. Pooling relevant results revealed that out of 59 exposed mammals only one developed tumour cell implantation at a site of colonic mucosal damage. This equates to a mammalian in vivo experimental risk of malignant cell implantation of 1.6%. CONCLUSION: The topic of colorectal cancer seeding following endoscopic procedures has received little attention. This review suggests that in the presence of a proximal colonic carcinoma there is a negligible risk of malignant implantation if a more distal polyp is endoscopically excised.

Size of metastatic deposits affects prognosis in patients undergoing pulmonary metastectomy for colorectal cancer.

INTRODUCTION: Pulmonary metastectomy for colorectal cancer (CRC) is a well accepted procedure although data regarding indications and prognostic outcomes are inconsistent. This study aimed to analyse our experience with resection of pulmonary CRC metastases to evaluate clinically relevant prognostic factors affecting survival. METHODS: A retrospective analysis was undertaken of the records of all patients with pulmonary metastases from CRC who underwent a thoracotomy between 2004 and 2010 at a single surgical centre. RESULTS: Sixty-six patients with pulmonary metastases from the colon (n=34) and the rectum (n=32) were identified. The 30-day hospital mortality rate was 0%, with 63 patients undergoing a R0 resection and 3 having a R1 resection. The median survival was 45 months and the cumulative 3-year survival rate was 61%. Size of pulmonary metastasis and ASA (American Society of Anesthesiologists) grade were statistically significant prognostic factors (p=0.047 and p=0.009 respectively) with lesions over 20mm associated with a worse prognosis. Sex, age, site, disease free interval (cut-off 36 months), primary tumour stage, hepatic metastases, number of metastases (solitary vs multiple), type of operation (wedge vs lobe resection), hilar lymph node involvement and administration of adjuvant chemotherapy were not found to be statistically significant prognostic factors. CONCLUSIONS: Pulmonary metastectomy has a potential survival benefit for patients with metastatic CRC. Improved survival even in the presence of hepatic metastases or multiple pulmonary lesions justifies aggressive surgical management in carefully selected patients. In our cohort, size of metastatic deposit was a statistically significant poor prognostic factor.