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.

The combination of two differently charged polypeptides, poly-L-lysine (PL) and poly-L-glutamate (PG), has shown excellent postsurgical antiadhesive properties. However, the high molecular, positively charged PL is toxic in high doses, proposed as lysis of red blood cells. This study aims to elucidate the in vivo toxicity and biodistribution of PL and complex bound PLPG comparing intravenous and intraperitoneal administration. Fifty-six Sprague-Dawley rats were used in a model with repeated blood samples within 30 min examining blood gases and blood smears. Similarly, FITC labelled PL were used to track bio distribution and clearance of PL, given as single dose and complex bound to PG after intravenous and intraperitoneal administration. Tissue for histology and immunohistochemistry was collected. Blood gases and blood smears as well as histology points to a toxic effect of high dose PL given intravenously but not after intraperitoneal administration. The toxic effect is exerted through endothelial disruption and subsequent bleeding in the lungs, provoking sanguineous lung edema. FITC-labelled PL experiments reveal a rapid clearance with differences between routes and complex binding. This study advocates a new theory of the toxic effects in vivo of high molecular PL. PLPG complex is safe to use as antiadhesive prevention based on this toxicity study given that PL is always intraperitoneally administered in combination with PG and that the dose is adequate.

Age, postoperative complications and the presence of lymph node metastases affect the likelihood of receiving adjuvant chemotherapy after PDAC surgery.

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.

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.

Background: Perioperative fluid overload has been reported to increase complications after a variety of operative procedures. This study was conducted to investigate the incidence of fluid retention after pancreatic resection and its association with postoperative complications. Methods: Data from 1174 patients undergoing pancreatoduodenectomy between 2010 and 2016 were collected from the Swedish National Pancreatic and Periampullary Cancer Registry. Early postoperative fluid retention was defined as a weight gain 2 kg on postoperative day 1. Outcome measures were overall complications, as well as procedure-specific complications. Results: The weight change on postoperative day 1 ranged from −1 kg to +9 kg. A total of 782 patients (66.6%) were considered to have early fluid retention. Patients with fluid retention had significantly higher rates of total complications (p = 0.002), surgical complications (p = 0.001), pancreatic anastomotic leakage (p = 0.018) and wound infection (p = 0.023). Multivariable logistic regression confirmed early fluid retention as an independent risk factor for total complications (OR 1.46; p = 0.003), surgical complications (OR 1.49; p = 0.002), pancreatic anastomotic leakage (OR 1.48; p = 0.027) and wound infection (OR 1.84; p = 0.023). Conclusions: Fluid retention is common after elective pancreatic resection, and its associated with an increased rate of postoperative complications.

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.

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