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.

Echinacea purpurea-derived alkylamides exhibit potent anti-inflammatory effects and alleviate clinical symptoms of atopic eczema.

BACKGROUND: Atopic eczema (AE) is a chronic inflammatory and pruritic skin disease. There is still an unmet need for topical anti-inflammatory and anti-pruritic substances exhibiting an excellent safety profile. The endocannabinoid system is known to regulate various aspects of cutaneous barrier and immune functions, thus targeting it may be a valid approach for alleviating the symptoms of AE. OBJECTIVE: To assess the putative efficacy of Echinacea purpurea-derived alkylamides (Ec. extract) activating cannabinoid (CB)-2 receptors in exerting anti-inflammatory effects and alleviating symptoms of AE. METHODS: In vitro anti-inflammatory efficiency was investigated by monitoring the effects of Ec. extract on poly-(I:C)-induced pro-inflammatory cytokine expression (Q-PCR) and release (ELISA) of HaCaT keratinocytes. Irritancy and sensitization potential (assessed by Human Repeat Insult Patch Test; Clinical trial 1); clinical efficiency in alleviating symptoms of AE (Clinical trial 2) as well as effects on human skin structure and lipid content (Clinical trial 3 followed by transmission electron microscopy and HPTLC) were investigated in randomized double blind clinical trials. RESULTS: Ec. extract significantly reduced mRNA expression as well as release of poly-(I:C)-induced pro-inflammatory cytokines (IL-6 and IL-8) in keratinocytes. Thus, not surprisingly, the well-tolerated (Clinical trial 1) Ec. extract-based cream reduced local SCORAD statistically significantly, not only compared to baseline, but also compared to the comparator (Clinical trial 2). Of great importance, besides the in vitro anti-inflammatory effects, administration of the Ec. extract-based cream also resulted in significantly higher levels of overall epidermal lipids, ceramide EOS (ω-esterified fatty acid+sphingosine sphingoid base), and cholesterol at Day 15 compared to baseline as well as significantly greater numbers of intercellular lipid lamellae in the intercellular space (Clinical trial 3). CONCLUSION: The investigated Ec. extract shows great potential in alleviating cutaneous symptoms of AE, and by exerting remarkable anti-inflammatory actions and restoring the epidermal lipid barrier, it will be very likely a well-tolerated, powerful novel ingredient for the adjuvant therapy of AE.

Differential effectiveness of selected non-psychotropic phytocannabinoids on human sebocyte functions implicates their introduction in dry/seborrhoeic skin and acne treatment.

Acne is a common skin disease characterized by elevated sebum production and inflammation of the sebaceous glands. We have previously shown that a non-psychotropic phytocannabinoid ((-)-cannabidiol [CBD]) exerted complex anti-acne effects by normalizing 'pro-acne agents'-induced excessive sebaceous lipid production, reducing proliferation and alleviating inflammation in human SZ95 sebocytes. Therefore, in this study we aimed to explore the putative anti-acne effects of further non-psychotropic phytocannabinoids ((-)-cannabichromene [CBC], (-)-cannabidivarin [CBDV], (-)-cannabigerol [CBG], (-)-cannabigerovarin [CBGV] and (-)-Δ(9) -tetrahydrocannabivarin [THCV]). Viability and proliferation of human SZ95 sebocytes were investigated by MTT and CyQUANT assays; cell death and lipid synthesis were monitored by DilC1 (5)-SYTOX Green labelling and Nile Red staining, respectively. Inflammatory responses were investigated by monitoring expressions of selected cytokines upon lipopolysaccharide treatment (RT-qPCR, ELISA). Up to 10 µm, the phytocannabinoids only negligibly altered the viability of the sebocytes, whereas high doses (≥50 µm) induced apoptosis. Interestingly, basal sebaceous lipid synthesis was differentially modulated by the substances: CBC and THCV suppressed it, and CBDV had only minor effects, whereas CBG and CBGV increased it. Importantly, CBC, CBDV and THCV significantly reduced arachidonic acid (AA)-induced 'acne-like' lipogenesis. Moreover, THCV suppressed proliferation, and all phytocannabinoids exerted remarkable anti-inflammatory actions. Our data suggest that CBG and CBGV may have potential in the treatment of dry-skin syndrome, whereas CBC, CBDV and especially THCV show promise to become highly efficient, novel anti-acne agents. Moreover, based on their remarkable anti-inflammatory actions, phytocannabinoids could be efficient, yet safe novel tools in the management of cutaneous inflammations.

[Pancreatic cancer. Evidence based management guidelines of the Hungarian Pancreatic Study Group]. / Pancreasrák. A Magyar Hasnyálmirigy Munkacsoport bizonyítékon alapuló kezelési irányelvei.

Pancreatic cancer is a disease with a poor prognosis usually diagnosed at a late stage. Therefore, screening, diagnosis, treatment and palliation of pancreatic cancer patients require up-to-date and evidence based management guidelines. The Hungarian Pancreatic Study Group proposed to prepare an evidence based guideline based on the available scientific evidence and international guidelines. The preparatory and consultation board appointed by the Hungarian Pancreatic Study Group translated and complemented/modified the recent international guidelines. 37 clinical statements in 10 major topics were defined (Risk factors and genetics, Screening, Diagnosis, Staging, Surgical care, Pathology, Systemic treatment, Radiation therapy, Palliation and supportive care, Follow-up and recurrence). Evidence was graded according to the National Comprehensive Cancer Network (NCCN) grading system. The draft of the guideline was presented and discussed at the consensus meeting in September 12, 2014. Statements were accepted with either total (more than 95% of votes, n = 15) or strong agreement (more than 70% of votes, n = 22). The present guideline is the first evidence-based pancreatic cancer guideline in Hungary that provides a solid ground for teaching purposes, offers quick reference for daily patient care and guides financing options. The authors strongly believe that these guidelines will become a standard reference for pancreatic cancer treatment in Hungary.

Optimal duration and timing of adjuvant chemotherapy after definitive surgery for ductal adenocarcinoma of the pancreas: ongoing lessons from the ESPAC-3 study.

PURPOSE: Adjuvant chemotherapy improves patient survival rates after resection for pancreatic adenocarcinoma, but the optimal duration and time to initiate chemotherapy is unknown. PATIENTS AND METHODS: Patients with pancreatic ductal adenocarcinoma treated within the international, phase III, European Study Group for Pancreatic Cancer-3 (version 2) study were included if they had been randomly assigned to chemotherapy. Overall survival analysis was performed on an intention-to-treat basis, retaining patients in their randomized groups, and adjusting the overall treatment effect by known prognostic variables as well as the start time of chemotherapy. RESULTS: There were 985 patients, of whom 486 (49%) received gemcitabine and 499 (51%) received fluorouracil; 675 patients (68%) completed all six cycles of chemotherapy (full course) and 293 patients (30%) completed one to five cycles. Lymph node involvement, resection margins status, tumor differentiation, and completion of therapy were all shown by multivariable Cox regression to be independent survival factors. Overall survival favored patients who completed the full six courses of treatment versus those who did not (hazard ratio [HR], 0.516; 95% CI, 0.443 to 0.601; P < .001). Time to starting chemotherapy did not influence overall survival rates for the full study population (HR, 0.985; 95% CI, 0.956 to 1.015). Chemotherapy start time was an important survival factor only for the subgroup of patients who did not complete therapy, in favor of later treatment (P < .001). CONCLUSION: Completion of all six cycles of planned adjuvant chemotherapy rather than early initiation was an independent prognostic factor after resection for pancreatic adenocarcinoma. There seems to be no difference in outcome if chemotherapy is delayed up to 12 weeks, thus allowing adequate time for postoperative recovery.

Pancreatic cancer hENT1 expression and survival from gemcitabine in patients from the ESPAC-3 trial.

BACKGROUND: Human equilibrative nucleoside transporter 1 (hENT1) levels in pancreatic adenocarcinoma may predict survival in patients who receive adjuvant gemcitabine after resection. METHODS: Microarrays from 434 patients randomized to chemotherapy in the ESPAC-3 trial (plus controls from ESPAC-1/3) were stained with the 10D7G2 anti-hENT1 antibody. Patients were classified as having high hENT1 expression if the mean H score for their cores was above the overall median H score (48). High and low hENT1-expressing groups were compared using Kaplan-Meier curves, log-rank tests, and Cox proportional hazards models. All statistical tests were two-sided. RESULTS: Three hundred eighty patients (87.6%) and 1808 cores were suitable and included in the final analysis. Median overall survival for gemcitabine-treated patients (n = 176) was 23.4 (95% confidence interval [CI] = 18.3 to 26.0) months vs 23.5 (95% CI = 19.8 to 27.3) months for 176 patients treated with 5-fluorouracil/folinic acid (χ(2) 1=0.24; P = .62). Median survival for patients treated with gemcitabine was 17.1 (95% CI = 14.3 to 23.8) months for those with low hENT1 expression vs 26.2 (95% CI = 21.2 to 31.4) months for those with high hENT1 expression (χ(2)1= 9.87; P = .002). For the 5-fluorouracil group, median survival was 25.6 (95% CI = 20.1 to 27.9) and 21.9 (95% CI = 16.0 to 28.3) months for those with low and high hENT1 expression, respectively (χ(2)1 = 0.83; P = .36). hENT1 levels were not predictive of survival for the 28 patients of the observation group (χ(2)1 = 0.37; P = .54). Multivariable analysis confirmed hENT1 expression as a predictive marker in gemcitabine-treated (Wald χ(2) = 9.16; P = .003) but not 5-fluorouracil-treated (Wald χ(2) = 1.22; P = .27) patients. CONCLUSIONS: Subject to prospective validation, gemcitabine should not be used for patients with low tumor hENT1 expression.

Effect of adjuvant chemotherapy with fluorouracil plus folinic acid or gemcitabine vs observation on survival in patients with resected periampullary adenocarcinoma: the ESPAC-3 periampullary cancer randomized trial.

CONTEXT: Patients with periampullary adenocarcinomas undergo the same resectional surgery as that of patients with pancreatic ductal adenocarcinoma. Although adjuvant chemotherapy has been shown to have a survival benefit for pancreatic cancer, there have been no randomized trials for periampullary adenocarcinomas. OBJECTIVE: To determine whether adjuvant chemotherapy (fluorouracil or gemcitabine) provides improved overall survival following resection. DESIGN, SETTING, AND PATIENTS: The European Study Group for Pancreatic Cancer (ESPAC)-3 periampullary trial, an open-label, phase 3, randomized controlled trial (July 2000-May 2008) in 100 centers in Europe, Australia, Japan, and Canada. Of the 428 patients included in the primary analysis, 297 had ampullary, 96 had bile duct, and 35 had other cancers. INTERVENTIONS: One hundred forty-four patients were assigned to the observation group, 143 patients to receive 20 mg/m2 of folinic acid via intravenous bolus injection followed by 425 mg/m2 of fluorouracil via intravenous bolus injection administered 1 to 5 days every 28 days, and 141 patients to receive 1000 mg/m2 of intravenous infusion of gemcitabine once a week for 3 of every 4 weeks for 6 months. MAIN OUTCOME MEASURES: The primary outcome measure was overall survival with chemotherapy vs no chemotherapy; secondary measures were chemotherapy type, toxic effects, progression-free survival, and quality of life. RESULTS: Eighty-eight patients (61%) in the observation group, 83 (58%) in the fluorouracil plus folinic acid group, and 73 (52%) in the gemcitabine group died. In the observation group, the median survival was 35.2 months (95%% CI, 27.2-43.0 months) and was 43.1 (95%, CI, 34.0-56.0) in the 2 chemotherapy groups (hazard ratio, 0.86; (95% CI, 0.66-1.11; χ2 = 1.33; P = .25). After adjusting for independent prognostic variables of age, bile duct cancer, poor tumor differentiation, and positive lymph nodes and after conducting multiple regression analysis, the hazard ratio for chemotherapy compared with observation was 0.75 (95% CI, 0.57-0.98; Wald χ2 = 4.53, P = .03). CONCLUSIONS: Among patients with resected periampullary adenocarcinoma, adjuvant chemotherapy, compared with observation, was not associated with a significant survival benefit in the primary analysis; however, multivariable analysis adjusting for prognostic variables demonstrated a statistically significant survival benefit associated with adjuvant chemotherapy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00058201.

Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine following pancreatic cancer resection: a randomized controlled trial.

CONTEXT: Adjuvant fluorouracil has been shown to be of benefit for patients with resected pancreatic cancer. Gemcitabine is known to be the most effective agent in advanced disease as well as an effective agent in patients with resected pancreatic cancer. OBJECTIVE: To determine whether fluorouracil or gemcitabine is superior in terms of overall survival as adjuvant treatment following resection of pancreatic cancer. DESIGN, SETTING, AND PATIENTS: The European Study Group for Pancreatic Cancer (ESPAC)-3 trial, an open-label, phase 3, randomized controlled trial conducted in 159 pancreatic cancer centers in Europe, Australasia, Japan, and Canada. Included in ESPAC-3 version 2 were 1088 patients with pancreatic ductal adenocarcinoma who had undergone cancer resection; patients were randomized between July 2000 and January 2007 and underwent at least 2 years of follow-up. INTERVENTIONS: Patients received either fluorouracil plus folinic acid (folinic acid, 20 mg/m(2), intravenous bolus injection, followed by fluorouracil, 425 mg/m(2) intravenous bolus injection given 1-5 days every 28 days) (n = 551) or gemcitabine (1000 mg/m(2) intravenous infusion once a week for 3 of every 4 weeks) (n = 537) for 6 months. MAIN OUTCOME MEASURES: Primary outcome measure was overall survival; secondary measures were toxicity, progression-free survival, and quality of life. RESULTS: Final analysis was carried out on an intention-to-treat basis after a median of 34.2 (interquartile range, 27.1-43.4) months' follow-up after 753 deaths (69%). Median survival was 23.0 (95% confidence interval [CI], 21.1-25.0) months for patients treated with fluorouracil plus folinic acid and 23.6 (95% CI, 21.4-26.4) months for those treated with gemcitabine (chi(1)(2) = 0.7; P = .39; hazard ratio, 0.94 [95% CI, 0.81-1.08]). Seventy-seven patients (14%) receiving fluorouracil plus folinic acid had 97 treatment-related serious adverse events, compared with 40 patients (7.5%) receiving gemcitabine, who had 52 events (P < .001). There were no significant differences in either progression-free survival or global quality-of-life scores between the treatment groups. CONCLUSION: Compared with the use of fluorouracil plus folinic acid, gemcitabine did not result in improved overall survival in patients with completely resected pancreatic cancer. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00058201.

Longitudinal quality of life data can provide insights on the impact of adjuvant treatment for pancreatic cancer-Subset analysis of the ESPAC-1 data.

The European Study Group for Pancreatic Cancer (ESPAC-1) study is the largest study of adjuvant treatment for pancreatic ductal adenocarcinoma to date and confirmed a survival advantage for adjuvant chemotherapy but not for chemoradiation. The importance of parallel evaluation of survival and quality of life (QoL) has been recognized as fundamental and the aim was to assess QoL and quality adjusted survival. A longitudinal QoL study on a subset of ESPAC-1 patients who prospectively completed the EORTC QLQ C-30 questionnaire during treatment and follow-up. An integrated quality-survival product method was used to adjust any treatment effect on survival by a function of measured QoL, calculated over a restricted 24-month-period (QALM-24). Three hundred and sixteen patients completed 1,201 questionnaires. There were no differences between treatment groups in dimension scores at baseline (randomization). For the chemotherapy group, the mean Quality Adjusted Life Months over 24 months (QALM-24) was 9.6 (95% CI: 8.7, 11.2) months compared with the mean QALM-24 of 8.6 (95% CI: 7.6, 10.5) months for the no chemotherapy group. For the chemoradiation group, the mean QALM-24 was 7.1 (95% CI: 6.0, 9.0) months compared with the mean QALM-24 of 8.1 (95% CI: 7.0, 10.0) months for the no chemoradiation group. The previously reported survival advantage supporting the use of adjuvant chemotherapy is maintained when adjusted using quality adjusted survival methodology. Chemotherapy provided on average an additional 1.0 quality-adjusted life months within a restricted 2-year time period from the time of resection.

Early enteral nutrition in acute pancreatitis--benefits and limitations.

INTRODUCTION: The application of enteral feeding as part of the treatment of acute pancreatitis goes back more than a decade now. In this review, the authors outline the indications and limitations of enteral feeding in the treatment of acute pancreatitis using up-to-date evidence-based data. RESULTS AND DISCUSSION: Latest meta-analyses suggest that early enteral feeding reduces effectively the incidence of infective complications and shortens hospital stay. In addition, recently published randomized controlled trials indicate that it may reduce mortality as well. CONCLUSION: However, the role of immune-enhancing ingredients, such as glutamine or omega-3 fatty acids, combined with enteral nutrition is uncertain, and the published studies are too few to make any treatment recommendation. Supplementation of enteral feeding with probiotics is a potentially promising alternative, but further well-designed multi-centric trials are necessary to prove their role in the treatment of acute pancreatitis.

Synbiotic control of inflammation and infection in severe acute pancreatitis: a prospective, randomized, double blind study.

BACKGROUND/AIMS: Experimental and clinical studies demonstrated that probiotics containing lactobacilli significantly improve the outcome of acute pancreatitis. In a prospective, randomized, double-blinded study the role of "Synbiotic 2000", a new synbiotic composition with high colony forming unit (CFU) was evaluated in the treatment of severe acute pancreatitis. METHODOLOGY: Patients with severe acute pancreatitis were randomized into two groups. Nasojejunal feeding was commenced within 24 hours after admission in both groups and continued for at least seven days. The first group of patients received four different lactobacilli preparations with 1010 CFU, respectively, and prebiotics containing four bioactive fibers (inulin, beta-glucan, resistant starch and pectin) in addition. Patients in the second (control) group received only prebiotics. RESULTS: 62 patients with severe acute pancreatitis completed the study. Altogether 8 patients died. Lower incidence of multiorgan failure (MOF), septic complications and mortality were detected in the first group compared to the control, but the differences were not significant statistically. The total incidence of systemic inflammatory response syndrome (SIRS) and MOF were significantly different between the two groups (8 vs. 14; p < 0.05). Furthermore, the number patients recovering with complications were significantly less in the first group receiving modern synbiotic therapy compared to the control (p < 0.05). Finally, lower rate of late (over 48 hours) organ failure was detected in the first versus the control group (3.0% vs. 17.2%). CONCLUSIONS: The results suggest that early nasojejunal feeding with synbiotics may prevent organ dysfunctions in the late phase of severe acute pancreatitis. In addition, the data also indicate that the infection of pancreatic necrosis may be associated with early phase organ failure.

[Combination of early nasojejunal feeding with modern synbiotic therapy in the treatment of severe acute pancreatitis (prospective, randomized, double-blind study)]. / Jejunális táplálás és korszeru synbiotikum kombinációja súlyos acut pancreatitisben.

BACKGROUND: We showed previously that probiotics containing lactobacilli significantly improve the outcome of acute pancreatitis. "Synbiotic 2000", a new synbiotic composition with high colony forming unit (CFU) comprises four different types of pre- and probiotics. In this prospective, randomized, double-blind study we evaluated the role of "Synbiotic 2000" in the treatment of severe acute pancreatitis. METHODS: Patients with severe acute pancreatitis were randomized into two groups. Nasojejunal feeding was commenced within 24 hours after admission in both groups and continued for at least seven days. The first group of patients received four different lactobacilli preparations with 10(10) CFU, respectively, and prebiotics containing four bioactive fibres (inulin, beta-glucan, resistant starch and pectin) in addition. Patients in the second (control) group received only prebiotics. RESULTS: 62 patients with severe acute pancreatitis completed the study. Altogether 8 patients died. We detected lower incidence of multiorgan failure (MOF), septic complications and mortality in the first group compared to the control, but the differences were statistically not significant. The total incidence of systemic inflammatory response syndrome (SIRS) and MOF were significantly different between the two groups (8 vs. 14; p < 0.05). Furthermore, the number patients recovering with complications were significantly less in the first group receiving modern synbiotic therapy compared to the control (p < 0.05). Finally, we found lower rate of late (over 48 hours) organ failure in the first versus the control group (3.0% vs. 17.2%). CONCLUSION: Our results suggest that early nasojejunal feeding with synbiotic may prevent organ dysfunctions in the late phase of severe acute pancreatitis. In addition, our data also indicate that the infection of pancreatic necrosis may be associated with early phase organ failure.

[Membranous constriction of the colon caused by non-steroidal anti-inflammatory drugs--case report]. / Nem szteroid gyulladáscsökkentó gyógyszer indukálta membranosus vastagbélszúkület--esetismertetés.

A 79-year-old female patient with rheumatoid arthritis treated with NSAIDs on long-term developed iron-deficiency anaemia and subsequently subacute intestinal obstruction. Barium enema showed multiple diaphragm-like strictures. At colonoscopy the lumen of the ascending colon was divided into compartments by multiple thin circumferential mucosal membranes. Right hemicolectomy was carried out. The histology of the resected specimen confirmed diaphragm disease of the large bowel. Diagnosis is usually difficult, even at laparotomy, due to the poor external presence of the disease. Such lesions are rare (about 10 cases have been reported in the world literature) and are similar to those previously described in the small bowel. With the increasing world-wide use of NSAIDs, clinicians must be aware of this rare gastrointestinal complication, which may require emergency surgical intervention.

[Early jejunal nutrition with combined pre- and probiotics in acute pancreatitis--prospective, randomized, double-blind investigations]. / Korai jejunális táplálás pre- és probiotikummal történó kombinálása akut pancreatitisben--prospektív, randomizált, kettós-vak vizsgálatsorozat.

BACKGROUND: Development of infection of pancreatic tissue in patients with severe acute pancreatitis dramatically increases morbidity and mortality. Colonisation of the lower gastrointestinal tract and oropharynx, mostly with gram-negative but sometimes also gram-positive bacteria is known to precede the contamination of the pancreatic tissue by a few days. A few specific lactic acid bacteria such as Lactobacillus plantarum 299 were effective in preventing colonisation of the gut by potential pathogens, to reduce endotoxemia and to stimulate the gut-associated lymphatic system (GALT) and the immune system. METHODS: Patients with acute pancreatitis, arriving within 48 hours after onset of disease showing typical clinical picture and laboratory signs of pancreatitis (plasma amylase > 200 U/l, CRP > 150 mg/l and an Imrie-score = or > 3) were randomised into two groups During the first week the treatment group received a freeze-dried preparation containing 10(9) live Lactobacillus plantarum 299 together with an oat fibre substrate. The control group received a similar preparation, but the Lactobacillus plantarum 299 had been inactivated by heat. For seven days the treatment was repeated twice every day. The preparations were delivered to the hospital in sachets so the content was unknown to the investigators, staff and patients. RESULTS: Forty five patients completed the study before there was indication that one group differed from the other in a statistically significant way, at which time the study was discontinued and the code broken. At this time 22 patients had received treatment with live and 23 patients with heat-killed Lactobacillus plantarum 299. Infected necrosis and abscesses occurred in 1/22 (4.5%) in the treatment group vs. 7/23 (30%) (p = 0.023) in the control group. The length of stay was 13.7 days in the treatment group vs. 21.4 days in the control group (not statistically significant). CONCLUSIONS: Supplementing Lactobacillus plantarum 299 is an effective tool to prevent pancreatic sepsis, to reduce the number of operations and length of stay. The only patient who developed sepsis in the treatment group did so eight days after the treatment had been discontinued. One week treatment, as in the present study, is too short. It should be provided for at least 2 weeks, or more appropriately, as long as the patients are treated with antibiotics or have signs of GI colonisation.