Risk factors and outcomes for patients with pancreatic cancer undergoing surgical exploration without resection due to metastatic disease:A national cohort study

Background:Unresectable disease is sometimes diagnosed during surgery in patients with pancreatic ductal adenocarcinoma(PDAC).This study aimed to identify preoperative risk factors for metastatic disease diagnosed at surgical exploration and to investigate and compare survival in resected and nonresected patients.Methods:Patients were identified from the Swedish National Pancreatic and Periampullary Cancer Registry 2010-2018.Predictors of metastatic disease were evaluated with a multivariable logistic regression model,and survival was evaluated with Kaplan-Meier estimates and log-rank tests.Results:In total,1938 patients with PDAC were scheduled for surgery.An unresectable situation was diagnosed intraoperatively in 399 patients(20.6%),including 234(12.1%)with metastasized disease.Independent risk factors for metastasis were involuntary weight loss(OR=1.72;95%CI:1.27-2.33)and elevated carbohydrate antigen 19-9(CA19-9)(35-599 U/m L,OR=1.79,95%CI:1.11-2.89;≥600 U/m L,OR=3.24,95%CI:2.04-5.17).Overall survival was lower among patients with metastasized disease than that among patients with a resectable tumor(P<0.001).Conclusions:Involuntary weight loss and an elevation of CA19-9 are preoperative risk factors for diagnosing metastasized disease during surgical exploration.

The Effects of Surgical Exploration on Survival of Unresectable Pancreatic Carcinoma:A Retrospective Case-Control Study

Background: Surgery may trigger the release of inflammatory factors, including cytokines, growth factors and angiogenic factors, which may stimulate tumor growth and progression. The present study was undertaken to evaluate the impact of surgical exploration on survival of patients with potentially resectable pancreatic cancer, who intraoperatively were found to have unresectable disease. Methods: Patients with pancreatic adenocarcinoma undergoing surgical exploration, without tumor resection, at our institution between 2009 and 2014, were selected and case-matched to patients who underwent primary palliative treatment. Results: A total of 116 patients were included. The surgical exploration group (n = 29) had significantly lower CRP levels at the time of diagnosis compared to the palliative controls (n = 87), 4 mg/L vs 12 mg/L;p = 0.004. The percentage of patients who received palliative chemotherapy was comparable between groups, but the time until start of chemotherapy was significantly longer in the surgical exploration group, 2 months vs 1 months;p Conclusion: In this case-control study, we could not detect any survival disadvantage due to surgical exploration in the setting of unresectable pancreatic cancer. Surgical exploration was associated with delayed start of palliative chemotherapy, but the percentage of patients who ultimately received chemotherapy was comparable to patients undergoing primary palliative treatment.

The influence on abdominal adhesions and inflammation in rabbits after exposure to differently charged polypeptides

Background: Abdominal adhesions develop on damaged peritoneal surfaces and constitute a significant health related problem. Previous animal studies have shown promising anti-adhesive effects when administering the polycation α-poly-L-lysine (αPL) and the polyanion poly-L-glutamate (PG) together. The objective of the study was to examine the effect of these differently charged polypeptides when administered by spraying and to evaluate any possible effect on fibrinolysis, fibrosis and inflammation. Methods: Rabbits were treated with PLPG after cecal abrasive surgery and analysis from peritoneal biopsies of active tPa/PAI-1 complex and from peritoneal fluid of IL-6 and active TGFb1 at day 0, 1, 4 and 10 were measured after surgery. Histological specimens were analyzed on day 10 regarding inflammation and fibrosis. Peritoneal adhesions were evaluated by adhesion score. All values were compared to the control group (NaCl). Results: PLPG-treated rabbits had a significant diminished adhesion score on day 10 as compared to the control group (p < 0.005). Significantly reduced collagen depositions on the peritoneum were seen in the PLPG group when evaluating the histological specimens (p < 0.05). No significant differences between the experimental and control groups were seen in peritoneal fluid when analyzing for active protein levels. Conclusion: This is the first study to investigate the effect on key parameters in adhesion formation as well as the preventive effect of the PLPG complex on abdominal adhesions in rabbits and also the first study where administration by spraying the polypeptides was used. PLPG was non-toxic in this setting and without significant differences in adhesion formation parameters and a significant reduction in adhesions was observed. This was verified both macroscopically and histologically.

Cationic polypeptides in a concept of oppositely charged polypeptides as prevention of postsurgical intraabdominal adhesions

Background: Two differently charged polypeptides, α-poly-L-lysine and poly-L-glutamate, have previously been shown to effectively reduce postoperative intraabdominal adhesions. Though α-poly-L-lysine showed toxicity in doses too close to the lowest therapeutic dose, the aim in the present study was to investigate the possible antiadhesive effect of another four cationic polypeptides. Materials/Methods: 125 mice were studied with a standardized and reproducible adhesion model and given epsilon poly-L-lysine, lactoferrin, lysozyme and polyarginine respectively in a combination with poly-L-glutamate. Epsilon poly-L-lysine was also tested in different concentrations and as single treatment. Results: All four cationic polypeptides above showed a significantly better anti-adhesive effect than the controls receiving saline (p<0.05). Epsilon poly-L-lysine had the best antiadhesive effect of the new substances tested in the experiment. Single treatment with the epsilon poly-L-lysine showed toxic side effects. Discussion: We have shown that epsilon poly-L-lysine, polyarginine, lysozyme and lactoferrin, in descending order, all can reduce postoperative intraabdominal adhesions in mice when combined with poly-L-glutamate. There were side effects of epsilon poly-L-lysine resembling those of α-poly-L-lysine, although less toxic. The antiadhesive effect of epsilon poly-L-lysine did not reach the level of α-poly-L-lysine. Further studies will concentrate on additional investigation, trying to modify the α-poly-L-lysine to lower its toxicity. The less toxic epsilon poly-L-lysine also needs further attention in our research of antiadhesive bioactive polypeptides.