Risk of Developing Pancreatic Cancer in Patients with Chronic Pancreatitis

Abstract

Background: Patients with chronic pancreatitis (CP) have an increased risk of developing pancreatic ductal adenocarcinoma (PDAC). We present data on PDAC in one of the most extensive European single-centre cohort studies of patients with CP. Methods: Retrospective analysis of prospectively collected data of patients with CP was performed. Aetiology of CP was determined according to the M-ANNHEIM classification system and only patients with definite CP > 18 years at data analysis were included. The final dataset included 581 patients with definite CP diagnosed between 2003 and 2018. Results: At CP diagnosis, there were 371 (63.9%) males and 210 (36.1%) females (median age 57 years, range 2–86). During 3423 person-years of observation, six pancreatic cancers were diagnosed (0.2% year). The mean time between diagnosis of CP and the occurrence of PDAC was 5.0 years (range 2.7–8.6). None of the cancer patients had a family history of PDAC. Diabetes mellitus (DM) was present in five of six (83.3%) patients with PDAC: in three patients before and in two after CP diagnosis. Clinical/laboratory signs of pancreatic exocrine insufficiency (PEI) were present in five of six (83.3%) patients with PDAC: in two at diagnosis of CP and in three after diagnosis. The mean survival time was 4 months after the diagnosis of PDAC (range 0.5–13). PDAC occurred significantly more often (p < 0.001) in two groups of patients without previous acute pancreatitis (AP): 2 of 20 patients (10%) with low body mass index (BMI) and PEI and in 3 of 10 (30%) patients with high BMI and DM at diagnosis of CP. Conclusions: Patients with CP have a high risk of developing PDAC, although risk is low in absolute terms. Our data suggest the possibility of defining subgroups of patients with a particularly elevated risk of PDAC. Such a possibility would open a path to personalised decision making on initiation of PDAC surveillance of patients with no previous episode of AP, (i) with low BMI and PEI, or (ii) elevated BMI and DM.

Pancreatic cancer: A review of epidemiology, trend, and risk factors

“…In recent decades, there is accumulating evidence that longstanding pre-existing chronic pancreatitis is a strong risk factor of developing pancreatic cancer[ 25 ]. Low body mass index and pancreatic exocrine insufficiency in patients with chronic pancreatitis define a high-risk population with latent PDAC[ 136 ]. In comparison with the general population, patients with chronic pancreatitis had a significantly increased risk of pancreatic cancer, especially those with an older age at onset and a > 60 pack-year smoking history[ 137 ].…”

Pancreas resident macrophage-induced fibrosis has divergent roles in pancreas inflammatory injury and PDAC

“…While still debated, multiple studies have shown that fibrosis can play a tumor supportive role, and some have even implicated macrophages in initiating or driving the fibrotic response (Chandler et al, 2019; DeNardo and Ruffell, 2019; Jiang et al, 2016; Zhang et al ., 2021). Fibrotic pathologies have also been linked to a higher risk of developing cancer, such as chronic pancreatitis being a significant risk factor for PDAC (Lowenfels et al, 1993; Vujasinovic et al, 2020). In addition to TRMs driving fibrosis, other studies have implicated TRMs in supporting tumor growth through distinct mechanisms.…”

Impact of surgery for chronic pancreatitis on the risk of pancreatic cancer: Untying the Gordian knot

“…The authors concluded that early onset and prolonged disease was a significant risk factor for CP-related PC. In another European study from Sweden, Vujasinovic et al [ 25 ] evaluated the risk of PC in a retrospective analysis of prospectively collected pancreatic clinical data. In contrast to other studies, they subclassified the CP patients into eight subgroups and calculated the PC risk.…”