Plasma Soluble Urokinase Plasminogen Activator Receptor (P-suPAR) in Pancreatic Diseases

Anu Aronen

Research output: Book/ReportDoctoral thesisCollection of Articles

Abstract

The pancreas is a complex organ with variety of functions and disease entities that may cause diverse challenges to medical professionals. Acute pancreatitis (AP) is a common disease, and although most patients recover completely, recurrent episodes may lead to chronic disease. Chronic pancreatitis (CP) is associated with impaired quality of life in addition to increased morbidity and health care costs. It would be extremely useful to identify the patient group at the highest risk for recurrences and development of CP.

Pancreatic cancer (PC) was the fourth most common cause of death from cancer in men and women in Europe in 2020. It is often asymptomatic in the early phases, and despite advanced diagnostics in addition to oncological and surgical treatment, survival remains poor. Diagnosing a pancreatic mass may be challenging. Malignant diseases should not be misdiagnosed, and at the same time, pancreatic surgery is associated with high mortality rate, thus false positive cases should be avoided. Postoperative complications may accumulate and lead to severe organ failure and even death.

Soluble urokinase plasminogen activator receptor (suPAR) is a soluble form of urokinase receptor and is measurable from venous blood. It is expressed by both benign and malignant cells and its concentration is associated with the level of immune activity in the human body. SuPAR levels have been shown to be elevated in various inflammatory and malignant diseases. Elevated levels are also associated with poorer prognosis. Plasma suPAR (P-suPAR) has been shown to predict various postoperative complications but has not been studied in relation to complications specific to pancreatic surgery.

This study explored the use of P-suPAR in the prediction and diagnostics of different pancreatic diseases. The aim was to predict 1) recurrent acute pancreatitis (RAP) after first acute alcohol-induced pancreatitis (AAP), 2) the development of CP after first AAP, 3) long-term mortality after first AAP, 4) postoperative complications after pancreatic resection, and 5) to investigate if P-suPAR could be used in diagnostics of PC.

In Study I patients with first AAP were prospectively followed up for a median seven years. Possible RAPs, development of CP, ten-year survival and P-suPAR from blood samples collected during control visits were registered. It was established that P-suPAR could not predict recurrence of AAP or development of CP. We found that elevated P-suPAR after recovery from first AAP was associated with higher ten- year mortality as an independent factor according to multivariate analysis.

Study II explored P-suPAR levels in those patients from Study I who developed CP during long-term follow-up. It was found that P-suPAR levels were not significantly elevated compared to those of follow-up patients with no CP. Evidence has been presented that suPAR levels are elevated in PC. We hypothesized that P- suPAR could be used to differentiate between CP and PC. It was found that P- suPAR is significantly higher in patients with PC than in patients with CP and this could possibly be used in differentiating between PC and CP.

Study III went further to consider if P-suPAR could be used to distinguish malignant pancreatic mass from non-malignant mass. The study population consisted of patients evaluated for pancreatic surgery for malignant-suspicious pancreatic mass. P-suPAR was shown to be significantly elevated in patients with malignant mass compared to patients with premalignant or benign mass. However, P-suPAR could not differentiate between premalignant and benign lesions.

Study IV explored if P-suPAR could predict complications after pancreatic surgery. P-suPAR was measured preoperatively and on postoperative days (PODs) 1 and 3. P-suPAR decreased postoperatively regardless of the outcome. No such postoperative P-suPAR profile has previously been reported. In addition, P-suPAR on POD 1 was significantly decreased in patients with postoperative pancreatic fistula, postoperative acute pancreatitis and surgical site infection, possibly reflecting a unique pattern of inflammation related to pancreas.

In conclusion, the aim of this thesis was to investigate P-suPAR levels in different pancreatic conditions in terms of prevention, diagnostics, and prognosis. P-suPAR after first AAP may help to focus preventive interventions on patients with the highest ten-year mortality risk. P-suPAR cannot be used in the prediction of RAPs or in the development of CP. When imaging shows a pancreatic mass, P-suPAR may be helpful as an additional tool in differentiating between a malignant lesion and a non-malignant one. As suPAR is a marker for an inflammatory state in the human body, postoperatively decreasing levels afford an interesting insight into systemic responses that may be specific to pancreatic surgery.
Original languageEnglish
Place of PublicationTampere
ISBN (Electronic)978-952-03-3036-1
Publication statusPublished - 2023
Publication typeG5 Doctoral dissertation (articles)

Publication series

NameTampere University Dissertations - Tampereen yliopiston väitöskirjat
Volume853
ISSN (Print)2489-9860
ISSN (Electronic)2490-0028

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