Daniel Åkerberg

Treatment of acute pancreatitis: focus on medical care.

Acute pancreatitis has an incidence of about 300 per 1 million individuals per year, of which 10–15% of patients develop the severe form of the disease. Novel management options, which have the potential to improve outcome, include initial proper fluid resuscitation, which maintains microcirculation and thereby potentially decreases ischaemia and reperfusion injury. The traditional treatment concept in acute pancreatitis, fasting and parenteral nutrition, has been challenged and early initiation of enteral feeding in severe pancreatitis and oral intake in mild acute pancreatitis is both feasible and provides some benefits. There are at present no data supporting immunonutritional supplements and probiotics should be avoided in patients with acute pancreatitis. There is also no evidence of any benefits provided by prophylactic antibacterials in patients with predicted severe acute pancreatitis. A variety of specific medical interventions have been investigated (e.g. intense blood glucose monitoring by insulin) but none has become clinically useful. Lessons can probably be learned from critical care in general, but studies are needed to verify these interventions in acute pancreatitis.

Toxicity and Dose Response of Intra-Abdominally Administered Poly-L-alpha-Lysine and Poly-L-Glutamate for Postoperative Adhesion Protection.

Background/Aims: Two differently charged polypeptides, poly-L-lysine (PL) and poly-L-glutamate (PG), have previously been shown to reduce postoperative intra-abdominal adhesions. This study aims to investigate the possible toxic effects and to establish a lowest effective antiadhesive dose. Methods: 152 mice were investigated with a well-known adhesion model and given different concentrations of the two differently charged polypeptides as well as only the cationic PL. Results: For the first time, a probable toxic level of PL given intraperitoneally (40 mg/kg) and the lowest significant concentration of PL and PG for antiadhesive purposes (1.6 mg/kg) could be established. Conclusion: The gap between the possible toxicity level of PL and the lowest efficient antiadhesive dose is probably too narrow, and the shape and charge of PL warrant continuous research for another polycation in the concept of differently charged polypeptides used as antiadhesive agents.

Effects of Polylysine and Polyglutamate on Inflammation and the Normal Process of Peritoneal Healing After Surgery

Introduction: Intraperitoneal adhesions are common after abdominal surgery and may lead to serious clinical complications. Previous studies have investigated the possible effects of the polypeptides poly-L-lysine (αPL) and poly-L-glutamate (PG) forming a polymer complex that prohibits local peritoneal adhesions after surgery. The aim of this study was to examine whether the normal process of peritoneal healing was affected by PL/PG polymer matrix. Material and methods: Male rats (Sprague Dawley) (n=84) underwent abdominal wall surgery and suturing. Rats were randomized in groups according to evaluation time (2, 4, 6, 8, 24 hours and 7 days) with corresponding control groups. Controls received saline (0.9%) and the experimental groups received PL/PG on the surgery site. tPA, PAI-1, IL-6 and active TGFb1 were analyzed at given time points postoperatively in peritoneal lavage. Adhesions were evaluated after seven days. Significant differences were considered to be p<0.05. Results: At a few individual time points small differences were seen between the groups (control and experiment) comparing levels of tPA, PAI-1, IL-6 and active TGFb1. When comparing levels of substances from all time points no statistical differences were seen between the groups as a total. Adhesions were significantly decreased on day 7, p=0.002. Conclusion: Despite significant reduction in adhesions PL/PG administered intraperitoneally as an anti-adhesion agent locally on surgically traumatized area does not seem to affect the normal process of peritoneal healing.

Re-evaluation of classical prognostic factors in resectable ductal adenocarcinoma of the pancreas

Pancreatic ductal adenocarcinoma carries a poor prognosis with annual deaths almost matching the reported incidence rates. Surgical resection offers the only potential cure. Yet, even among patients that undergo tumor resection, recurrence rates are high and long-term survival is scarce. Various tumor-related factors have been identified as predictors of survival after potentially curative resection. These factors include tumor size, lymph node disease, tumor grade, vascular invasion, perineural invasion and surgical resection margin. This article will re-evaluate the importance of these factors based on recent publications on the topic, with potential implications for treatment and outcome in patients with pancreatic cancer.

Prevention of pleural adhesions by bioactive polypeptides - a pilot study.

Objective: Postoperative pleural adhesions lead to major problems in repeated thoracic surgery. To date, no antiadhesive product has been proven clinically effective. Previous studies of differently charged polypeptides, poly-L-lysine (PL) and poly-L-glutamate (PG) have shown promising results reducing postoperative abdominal adhesions in experimental settings. This pilot study examined the possible pleural adhesion prevention by using the PL+PG concept after pleural surgery and its possible effect on key parameters; plasmin activator inhibitor-1 (PAI-1) and tissue growth factor beta 1 (TGFb) in the fibrinolytic process. Methods: A total of 22 male rats were used in the study, one control group (n=10) and one experimental group (n=12). All animals underwent primary pleural surgery, the controls receiving saline in the pleural cavity and the experimental group the PL+PG solution administered by spray. The animals were evaluated on day 7. Macroscopic appearance of adhesions was evaluated by a scoring system. Histology slides of the adhesions and pleural biopsies for evaluation of PAI-1 and TGFb1 were taken on day 7. Results: A significant reduction of adhesions in the PL+PG group (p<0.05) was noted at day 7 both regarding the length and severity of adhesions. There were no significant differences in the concentration of PAI-1 and TGFb1 when comparing the two groups. Conclusions: PL+PG may be used to prevent pleural adhesions. The process of fibrinolysis, and fibrosis was though not affected after PLPG administration.

Prevention of Adhesions by PL/PG after Adhesiolysis

Background: Previous studies of differently charged polypeptides, Poly-L-lysine (PL) and Poly-L-Glutamate (PG) have shown promising results, reducing postoperative adhesions. This study aimed to investigate the possible anti adhesion effect of those combined polypeptides, after adhesiolys. The concentration of tPA, PAI-1 and active TGFb1 in biopsies from adhesions, unharmed peritoneum before and after adhesiolysis, was also investigated. Materials and methods: A total of 24 male rats were divided in three groups A (N=8), B (N=8) and C (N=8). All rats underwent primary adhesion creating surgery at day 0, and adhesiolysis at day 7. Adhesions were evaluated at day 7 and 14, where group B received PL/PG after surgery at day 0 and after adhesiolysis at day 7, and group C received PL/PG after adhesiolysis at day 7. Tissue plasminogen activator (tPA), Plasminogen activator inhibitor 1(PAI-1) and active transforming growth factor beta 1(TGF-β1) were collected from biopsies of adhesions and normal peritoneum at day 0, 7 and 14. Results: Significant reduction of adhesions p<0.05 was seen in group B at day 7 after primary surgery, and at day 14 after adhesiolysis. Significantly p<0.05 reduction of adhesions was seen at day 14 after adhesiolysis in group C. Some variations were seen in tPA, PAI-1 and active TGFb1. Conclusions: PL/PG may be used to prevent adhesion formation after adhesiolysis. The process of fibrinolysis and fibrosis was not affected, after PL/PG prophylaxis and adhesiolysis.

Factors influencing receipt of adjuvant chemotherapy after surgery for pancreatic cancer : a two-center retrospective cohort study

Abstract Objective: The addition of adjuvant chemotherapy after surgical resection has improved survival rates for patients with pancreatic ductal adenocarcinoma (PDAC). However, outside clinical trials, many operated patients still do not receive adjuvant chemotherapy due to clinical and tumor-related factors. The aim of this study was to investigate factors that may influence the receipt of adjuvant chemotherapy and the effect on long-term survival. Materials and methods: Patients undergoing macroscopically curative resection for PDAC at the University Hospitals in Lund and Linköping, Sweden, between 1 January 2007 and 31 December 2015, were retrospectively reviewed. Clinical and pathological data were compared between adjuvant and non-adjuvant chemotherapy groups and factors affecting chemotherapy receipt were analyzed by multiple logistic regression. Multivariable Cox regression analysis was performed to select predictive variables for survival. Results: A total of 233 patients were analyzed. Adjuvant chemotherapy was administered to 167 patients (71.7%). The likelihood of receiving adjuvant chemotherapy decreased with age, OR 0.91, 95% CI 0.86–0.95, p < .001. Moreover, patients with severe postoperative complications (Clavien–Dindo grade ≥ III) were less likely to receive adjuvant chemotherapy, OR 0.31, 95% CI 0.14–0.71, p = .005. The presence of lymph node metastases on histopathological reporting was associated with increased likelihood of initiating adjuvant chemotherapy, OR 2.19, 95% CI 1.09–4.40, p = .028. Adjuvant chemotherapy was an independent factor for prolonged survival on multivariable Cox regression analysis, HR 0.45 (95% CI 0.31–0.65), p < .001. Conclusions: Age, postoperative complications and the presence of lymph node metastases affect the likelihood of receiving adjuvant chemotherapy after PDAC surgery.