Chronic pancreatitis: comprehensive analysis of epidemiological trends, disease evolution and clinical outcomes

Quammie, Shauntelle

Chronic pancreatitis: comprehensive analysis of epidemiological trends, disease evolution and clinical outcomes

Publication Date

July 31, 2026

Creator

Quammie, Shauntelle

University of Nottingham

Abstract

BACKGROUND Chronic pancreatitis (CP) is a progressive fibro-inflammatory disease characterised by irreversible pancreatic damage, chronic abdominal pain and loss of exocrine and endocrine function. Despite its significant morbidity and mortality, CP remains challenging to diagnose, particularly in early disease, due to heterogeneous clinical presentations and limitations of individual diagnostic modalities. Consequently, the true burden and broader clinical impact of CP are likely underestimated. METHODS This thesis employed a multi-method approach to comprehensively evaluate CP. A stringent, pragmatic, multi-source case ascertainment strategy was developed and applied within a UK tertiary centre to accurately identify patients with CP in routine clinical practice, addressing recognised diagnostic heterogeneity. This enabled robust estimation of incidence and prevalence. A systematic review and meta-analysis examined the association between CP and extra-pancreatic cancers. These findings were complemented by longitudinal cohort studies evaluating site-specific cancer risk, temporal patterns of cancer development and associated risk factors. Additional analyses assessed non-cancer comorbidities, pancreatic surgery and mortality. Finally, the burden and clinical significance of multi-organ fibrosis were examined to explore systemic involvement in CP. RESULTS From a screening cohort of 24,271 individuals undergoing pancreas-related investigations or treatment, 1,003 patients met stringent diagnostic criteria for CP. Reliance on single diagnostic modalities would have substantially underestimated disease burden. The median age at diagnosis was 65 years (IQR 50 – 76), with a male predominance (65.4%). The incidence of CP diagnosis increased by a mean of 4.1% per year over the study period, ranging from 8.5 to 13.8 per 100,000 population, while point prevalence rose progressively to 53.6 per 100,000 by the end of follow-up. Systematic review and meta-analysis demonstrated a significantly increased risk of extra-pancreatic malignancies in patients with CP, extending beyond the established association with pancreatic cancer. Cohort analyses confirmed an expanding cancer spectrum, with increased frequencies of both pancreatic and extra-pancreatic cancers. Smoking and alcohol exposure were strongly associated with cancer risk, and cancers occurred after variable latency following CP diagnosis, highlighting prolonged vulnerability over the disease course. Non-cancer comorbidities were highly prevalent and accumulated with disease duration. Pancreatogenic diabetes developed in a substantial proportion of patients, alongside cardiovascular and metabolic comorbidities. A proportion of patients required pancreatic surgery for pain or complications. Mortality was high and exceeded that expected in the general population, driven by both malignant and non-malignant complications of CP. Evidence of fibrosis affecting organs beyond the pancreas was frequently identified. These findings support the concept of CP as a systemic fibro-inflammatory condition rather than an isolated pancreatic disorder. CONCLUSION This thesis demonstrates that CP is a diagnostically challenging, multisystem disease associated with increasing incidence, substantial cancer risk, high comorbidity burden and premature mortality. Stringent case ascertainment is essential to accurately identify affected patients. Holistic, long-term clinical management strategies are required to address the full spectrum of disease burden and improve outcomes

Item Type

ethesis

Thesis Type

PhD

Supervisors

Aravinthan, Aloysious

University of Nottingham

Aithal, Guruprasad P.

University of Nottingham

Crooks, Colin J.

University of Nottingham

Keywords