Chronic pancreatitis is a progressive fibroinflammatory disease primarily caused by a complex interplay of environmental and genetic risk factors. It might result in pancreatic exocrine and endocrine insufficiency, chronic pain, reduced quality of life, and increased mortality. The diagnosis is based on the presence of typical symptoms and multiple morphological manifestations of the pancreas, including pancreatic duct stones and strictures, parenchymal calcifications, and pseudocysts. Management of chronic pancreatitis consists of prevention and treatment of complications, requiring a multidisciplinary approach focusing on lifestyle modifications, exocrine insufficiency, nutritional status, bone health, endocrine insufficiency, pain management, and psychological care. To optimise clinical outcomes, screening for complications and evaluation of treatment efficacy are indicated in all patients with chronic pancreatitis.

Diabetes in patients with chronic pancreatitis is a heterogeneous condition with some patients presenting with pre-existing diabetes and others developing diabetes after pancreatitis onset. We aimed to characterise beta and alpha cell function in these patients and examine differences between those with and without pre-existing diabetes.

We included 26 patients with chronic pancreatitis and insulin-treated diabetes, divided into two subgroups: 13 with pre-pancreatitis diabetes (having type 2 diabetes before their chronic pancreatitis diagnosis) and 13 with post-pancreatitis diabetes. Patients underwent comprehensive clinical characterisation, including an arginine stimulation test to measure fasting and stimulated levels of C-peptide and glucagon. Additionally, they were monitored with continuous glucose monitoring over 20 days.

Patients with chronic pancreatitis and diabetes exhibited reduced fasting and stimulated C-peptide and glucagon responses to arginine, though responses varied considerably among individuals. Post-pancreatitis diabetes patients had lower glucagon responses than those with pre-pancreatitis diabetes (mean difference -19.3 pmol/L, 95% confidence interval (CI) -35.6 to -3.0). However, C-peptide levels were similar between the groups. Pre-pancreatitis diabetes patients spent more time in level 2 hyperglycaemia compared to post-pancreatitis patients (12.9% vs. 6.7%, p = 0.02). In contrast, post-pancreatitis diabetes patients had more time in both level 1 and level 2 hypoglycaemia (p = 0.03 and p = 0.05, respectively). A low glucagon response was correlated with time spent in hypoglycaemia (Rho = -0.54, p < 0.01).

Diabetes in chronic pancreatitis is a heterogeneous entity. The presence of type 2 diabetes prior to chronic pancreatitis is associated with a reduced risk of alpha cell dysfunction and hypoglycaemia.

This study analyzes temporal trends of pancreatitis from 1990 to 2021 across 21 regions and 204 countries based on the Global Burden of Disease (GBD) database to inform prevention and treatment strategies.

Incidence, death, prevalence, and DALYs estimates for pancreatitis were derived from the GBD 2021, categorized by age, sex, and geographical location for the period 1990-2021. Mortality estimates were generated using the cause of death ensemble model.

The global age-standardized incidence and deaths of pancreatitis increased 1.59-fold and 1.79-fold from 1990 to 2021, respectively. The percentage change in global age-standardized incidence and death rate were -12.8% (-14.7% to -10.7%) and -14.1% (-24.5% to -1.1%). DALYs increased from 2.58 million in 1990 to 4.10 million in 2021. The incidence rates in 2021 ranged from 16.63 per 100 000 in Tropical Latin America, the lowest globally, to 99.35 per 100 000 in Eastern Europe, the highest. Greenland reported the highest country-specific incidence at 115.21 per 100 000, whereas Mozambique had the lowest at 0.81 per 100 000. The incidence and death rates were higher in males, with ratios of 1.27:1 and 1.94:1, respectively. The main contributors to pancreatitis was alcohol use.

Pancreatitis continues to exhibit a heavy burden on a global scale, particularly in Eastern Europe. Therefore, efficient prevention and control strategies targeting alcohol consumption are imperative in order to alleviate the substantial burden.

After an aetiological (first-line) workup, the cause of acute pancreatitis remains unidentified in a significant proportion of cases, a condition known as idiopathic acute pancreatitis (IAP).

Retrospective cohort study involving patients with presumed IAP referred for second-line aetiological workup. The completion of first-line aetiological evaluations was assessed upon referral, and the diagnostic outcomes of second-line investigations were evaluated. Over a one-year follow-up period, we documented acute pancreatitis recurrence and patient mortality. Recurrence risk was analysed using an age-adjusted Cox regression model, stratified by treatable versus non-treatable aetiologies.

We identified 161 patients with presumed IAP, among whom 81 (50%) had recurrent acute pancreatitis. In total, 115 patients (71%) had a complete first-line aetiological workup. The overall diagnostic yield of the second-line aetiological workup was 25% (95% confidence interval [CI] 18-32%). Among second-line tests, the highest diagnostic yield was found for endoscopic ultrasound (34%, 95% CI 20-50%) and genetic testing (37%, 95% CI 22-53%). The most frequent aetiologies identified were biliary pancreatitis (16 patients [10%]) and pancreatitis with a genetic mutation (15 patients [9%]). Neoplasia was identified in two patients. A treatable aetiology was associated with a numerically reduced pancreatitis recurrence risk (Hazard Ratio 0.50, 95% CI 0.07-3.85, p = 0.51). No patient died during the follow-up period.

A second-line aetiological workup can identify the aetiology in 25% of patients with presumed IAP. The most frequent aetiologies are biliary pancreatitis and pancreatitis with a genetic mutation.

Effective chronic pancreatitis (CP) treatment requires accurate severity evaluation, but no histopathology grading system exists. This study aimed to develop and validate a novel CP pathological grade (Histopathology-derived CPpG) using quantified pathological and radiological characteristics through deep learning.

Patients with pathologically/clinically confirmed CP or recurrent acute pancreatitis were retrospectively enrolled (2011-2023). Whole-slide CP images were automatically segmented and quantified via DeeplabV3+, followed by latent class analysis to develop Histopathology-derived CPpG. A deep learning radiomics score (DLRS) was created to predict Histopathology-derived CPpG using preoperative CT scans of patients with pathologically confirmed CP. CT-predicted CPpG was then validated in an independent group of patients with clinically confirmed CP and recurrent acute pancreatitis.

The study included 2054 patients with CP and recurrent acute pancreatitis, with 181 cases of pathologically confirmed CP. Histopathology-derived CPpG I had a higher proportion of acini, acinus-to-stroma ratio, acinus-to-islet ratio, islet-to-stroma ratio, and (acinus + islet)-to-stroma ratio, and a lower proportion of stroma and lymphocytes compared to CPpG II. The DLRS demonstrated high performance in the validation (AUC, 0.84; 95 % CI: 0.75-0.92) and test (AUC, 0.76; 95 % CI: 0.65-0.87) sets. In a large-scale clinical validation, CT-predicted grades were significantly associated with endocrine and exocrine function, as well as prognosis (P < .05).

This study developed a novel pathological classification, Histopathology-derived CPpG, which accurately reflects disease severity. Additionally, the non-invasive DLRS shows great potential for dynamically monitoring CP severity and evaluating pancreatic endocrine and exocrine function, as well as prognosis.

Chronic pancreatitis (CP) is a progressive inflammatory disease of the pancreas leading to permanent damage, resulting in both exocrine and endocrine insufficiency. Understanding the management of patients with CP and their outcomes is critical for improving patient care. CP is relatively rare in Italy and is characterised by various aetiologies and clinical progression requiring personalised treatment options. This registry (ITARECIPE) aims to prospectively collect and analyse data on patients with newly diagnosed CP to gain insights into its epidemiology, presentation, disease progression, and treatment outcomes.

This is a multicentre, observational, non-interventional incident cohort study supported by the Italian Association for the Study of the Pancreas and endorsed by relevant Italian gastroenterological societies. ITARECIPE is the first registry in Italy focusing on newly diagnosed CP patients, leading to a comprehensive understanding of disease onset and progression. The study plans to enrol ≥300 patients annually over a minimum of 5 years. Data are recorded in a pseudo-anonymous electronic Case Report Form (eCRF) at baseline and follow-up visits, covering patient demographics, comorbidities, chronic medications, CP aetiology, pancreatic function (exocrine and endocrine), pain, complications, imaging, laboratory tests and treatments. It will track epidemiology, clinical history and treatment outcomes, potentially improving adherence to best practices and informing health policy decisions. The ITARECIPE registry will contribute significantly to the understanding of CP by providing detailed epidemiological, clinical and examinations data into disease management, which could help the development of future clinical practice and guidelines.

The study was approved by the Ethics Committee (EC) of the promoter centre (San Raffaele Hospital, Milan, Italy; approval code 178/2022) and subsequently by the EC of each participating centre. All patients will be included after signing written informed consent and will be recorded in a pseudo-anonymous manner in a specific eCRF, in accordance with international principles and recommendations for observational studies. The ongoing results may be presented at national or international conferences and will be reported in peer-reviewed publications.

NCT05733130.

Acute pancreatitis (AP) recurrence rates range from 11 to 36 % yet accurately predicting recurrent acute pancreatitis (RAP) and its progression to chronic pancreatitis (CP) after an initial episode remains challenging. Thus, this study explored the risk factors contributing to RAP and its progression to CP.

This retrospective study included patients with AP from three tertiary medical centers between January 2010 and December 2017. The patients were followed up for up to 60 months. The primary endpoint was the incidence of RAP and CP; risk factors influencing these outcomes were also identified.

Overall, 501 patients were included, of which 164 (32.7 %) experienced RAP, and 71 (14.2 %) progressed to CP. The leading causes of AP were alcohol consumption (43.1 %), gallstones (41.5 %) and hypertriglyceridemia (4.4 %). Multivariate Cox regression analysis revealed that smoking (HR, 4.09; 95 % CI, 2.752-6.078, p < 0.001), and organ failure after 48 h of hospitalization (HR, 3.52; 95 % CI, 1.22-10.19, p < 0.02) were significant risk factors for RAP. Significant risk factors for progression to CP included age over 60 years (HR, 5.29; 95 % CI, 1.25-22.47, p = 0.024), smoking (HR, 2.50; 95 % CI, 1.04-6.01, p = 0.04), alcohol consumption (HR, 8.79; 95 % CI, 2.06-37.43, p = 0.003), computed tomography severity index (CTSI) (HR, 1.22; 95 % CI, 1.04-1.44, p = 0.015), and recurrence of AP (HR, 70.69; 95 % CI, 2.61-1914.86, p = 0.011). In alcohol-induced RAP patients, ≥3 recurrences (HR, 4.18; 95 % CI, 1.75-9.98, p = 0.001) was significant risk factor for progression to CP.

Alcohol consumption was the predominant cause of AP and RAP. The severity of the initial AP episode was the key determinant for RAP, and RAP was the most significant risk factor for the progression to CP. Therefore, smoking and alcohol cessation are important to prevent the development of recurrent AP and CP during long-term follow-up.

Mechanisms of pancreatic pain are insufficiently understood, and quantitative sensory testing (QST) may help to identify the underlying mechanisms. Accordingly, this study assessed comprehensive somatosensory profiles encompassing nociceptive and nonnociceptive parameters in 70 patients with distinct pancreatic diseases, namely acute (n = 23), chronic (n = 20), or autoimmune pancreatitis (n = 10) and pancreatic cancer (n = 17) and compared it with 30 healthy control subjects by standardized QST (protocol of the German research network on neuropathic pain). Patients with pancreatic diseases presented significant somatosensory deficits in all thermal and tactile detection and pain thresholds in the pancreatic viscerotome (Th10), when compared with a remote control area (dermatome C5) or reference data of matched healthy controls (P < 0.05-P < 0.0001). Unaltered vibration detection emphasizes the strictly regional character of losses. Loss of sensitivity paralleled the occurrence of paradoxical heat sensation (Th10 vs C5; P < 0.05), an indicator of thermal integration deficit. Punctate hyperalgesia or pain to light touch, the hallmark signs of spinal central sensitization were mostly absent and pain summation remained unchanged (P > 0.05). Stratification of patients revealed that somatosensory deficits were significantly more pronounced in acute compared with chronic pancreatitis (eg, cold and warm detection thresholds: -2.19 ± 1.42 vs -1.10 ± 1.23 and -1.30 ± 1.68 vs -0.11 ± 1.80 z-values; P < 0.05 each). Notably, blunt pressure hyperalgesia, the only somatosensory parameter exhibiting significant gain compared with the patients' remote C5 segment, was a frequent finding only in acute, but not in chronic pancreatitis. The somatosensory phenotype of patients with distinct pancreatic disorders was characterized by a wide array of sensory losses being most severe in acute pancreatitis.

Activation of type M2 macrophages has been implicated in the pathogenesis of chronic pancreatitis (CP). In a clinical pilot study, we investigated blood-based markers of macrophage activation at different stages of CP.

We performed a cross-sectional analysis of prospectively collected plasma samples from healthy controls and patients with suspected or definitive CP according to the M-ANNHEIM criteria. Plasma concentrations of soluble CD163 (sCD163), soluble CD206 (sCD206), and monocyte chemoattractant protein-1 (MCP-1) were analyzed using enzyme-linked immunosorbent assays. Group and pairwise comparisons of analytes were performed using regression models and area under the receiver operating curves (AUC-ROC).

In total, 73 subjects with CP (28 suspected CP and 45 definitive CP) and 40 controls were included. Compared to controls, the median plasma concentrations of sCD163 ( P  = 0.019) and sCD206 ( P  = 0.033) were elevated in patients with definitive CP. sCD206 was also elevated in patients with definitive CP ( P  = 0.042) compared to suspected CP. ROC analysis revealed the optimal sCD163 cutpoint to distinguish definitive CP from controls was 1.84 mg/mL (AUC-ROC 0.65; 95% confidence interval [CI], 0.54-0.77). The optimal sCD206 cutpoint to distinguish definitive CP from controls was 0.24 mg/mL (AUC-ROC 0.66; 95% CI, 0.54-0.78). MCP-1 concentrations showed no differences across subgroups.

Our study demonstrates that subjects with definitive CP, sampled during a clinically quiescent phase, exhibited increased levels of sCD163 and sCD206. This indicates the presence of activated M2 macrophages in patients with CP at advanced, but not early, clinical stages.

Acute on chronic pancreatitis (ACP) shares a similar clinical presentation with acute pancreatitis (AP) and is often diagnosed and treated in the same way. However, these two conditions may have distinct clinical risk profiles and prognoses. There is currently limited evidence available regarding the specific characteristics of ACP.

This retrospective cohort study included all adult patients admitted with a diagnosis of AP or ACP between 2017 and 2019 at two tertiary referral centers. The primary outcome was disease severity as defined by the Atlanta classification. Secondary outcomes included the presence of local and systemic complications, organ failure, ICU admission, and mortality. Differences in outcomes between ACP and AP were compared using multivariate logistic regression models, with results presented as odds ratios (ORs).

We included 1163 patients, 90% of whom had AP and 10% had ACP. ACP patients were predominantly male (81 vs. 46%; P  < 0.001), whereas AP patients were older (mean age 62.6 vs. 56.5 years, P  < 0.001). ACP patients had lower amylase and lipase levels ( P  < 0.001). Multivariate analysis showed no difference in the risk of moderate or severe pancreatitis (OR, 1.15; 95% CI, 0.66-1.98; P  = 0.615). ACP patients had a higher risk of local complications (predominantly pseudocysts) (OR, 1.71; 95% CI, 1.00-2.92; P  = 0.049) and a lower risk of organ failure ( P  = 0.019) and ICU admission ( P  = 0.005).

Our study confirms previous observations that ACP has a more favorable in-hospital prognosis than AP and extends these findings to a modern European setting.

With the exception of late-stage disease, making an accurate diagnosis of chronic pancreatitis remains a significant clinical challenge. Using established diagnostic criteria, a retrospective review from a VA cohort was performed to determine the level of confidence with which this diagnosis is applied. Evaluation for clinical factors associated with diagnostic confidence was performed.

Among 832 patient charts reviewed, 245 met inclusion criteria. Applying described diagnostic criteria, patients with a presumed diagnosis of chronic pancreatitis were evaluated for diagnostic confidence level at the time of diagnosis and again over time. Regression analysis was performed to determine clinical factors that were independently associated with a low-confidence diagnosis as well as change in diagnostic confidence over time.

57% of patients (n = 140) received a low-confidence diagnosis of chronic pancreatitis, with a more likely diagnosis identified in 67% of those cases, including underlying neoplasia (n = 12, 13%). Over 7.3 years of follow-up, 49% (n = 120) of patients maintained a low-confidence diagnosis. Alcohol use (OR 14.0; CI 1.3-111.1) and a history of acute pancreatitis (OR 12.8; CI 1.4-113.7) were associated with a change from low- to high-confidence diagnosis over time. PERT was prescribed frequently (60%, n = 148), despite low diagnostic confidence and infrequent objective testing for exocrine insufficiency (20%, n = 48).

Approximately, 50% of patients in a VA population clinically managed with a working diagnosis of chronic pancreatitis have low clinical confidence in that diagnosis. Increased diagnostic scrutiny and wider adoption of applicable diagnostic approaches are of the utmost importance.

Randomized trials have demonstrated the superiority of surgery over endoscopy in patients with symptomatic chronic pancreatitis. However, large international studies quantifying the impact of surgery on chronic pancreatitis are lacking. The aim of this study was to evaluate current practice across Europe regarding indications, surgical techniques, and outcomes of surgery for chronic pancreatitis.

A prospective multicentre study of consecutive patients undergoing surgery for symptomatic chronic pancreatitis from 22 centres in 13 countries from 1 June 2021 to 30 November 2022 was conducted. The outcome of interest in patients with pain as an indication was the Izbicki pain score at 6-month follow-up, with complete pain relief defined as an Izbicki pain score ≤10 and partial pain relief defined as an Izbicki pain score >10, but with a >50% decrease compared with the baseline score. Quality of life was assessed using Pancreatitis Quality of Life Instrument (PANQOLI) and 12-Item Short-Form (SF-12) surveys. Predictors of pain relief were analysed using multivariable analysis.

Overall, 207 patients underwent surgery (24.6% underwent surgical drainage procedures, 29.5% underwent duodenum-preserving head resections, and 45.9% underwent formal pancreatic resections). Before surgery, 48.8% used opioids and 51.2% had undergone prior endoscopic treatment. Major morbidity occurred in 14.0% and the 90-day mortality rate was 1.4%. Among 113 patients operated on for pain, the median Izbicki pain score decreased from 61.3 to 19.0 at 6 months (P < 0.001). Pain relief was achieved in 72.6% (43 patients reported complete pain relief and 39 patients reported partial pain relief). PANQOLI and SF-12 Physical Component Summary scores improved significantly (P < 0.001). Longer symptom duration (OR 0.95 (95% c.i. 0.90 to 1.00), P = 0.045) and use of opioids before surgery (OR 3.16 (95% c.i. 1.04 to 9.64), P = 0.043) predicted less pain relief.

Surgery for chronic pancreatitis across Europe was performed with low morbidity. Patients reported good pain relief and improvements in quality-of-life scores. Multidisciplinary consultation is recommended for all patients with chronic pancreatitis before undergoing any intervention.

To investigate the epidemiology and burden of adult-onset chronic pancreatitis (CP) in South Australia.

Retrospective case-control study; data linkage.

All public adult hospitals in SA.

Administrative data linkage from South Australia-Northern Territory DataLink was used to ascertain an index cohort of all adults with an initial diagnosis of CP aged >19 years between June 2000 and June 2019. Age- and sex-matched controls were drawn from the general population of SA, adults with type 1 diabetes mellitus and adults with type 2 diabetes mellitus (defined by International Classification of Diseases 10th Revision coding).

Hospital visits, days in hospital, emergency department visits, intensive care unit admissions, incidence, prevalence.

A total of 2503 incident index cases with CP were identified. The crude prevalence and incidence were estimated as 195.1 per 100 000 and 10.4 per 100 000 per annum, respectively. Cases of CP averaged more hospital visits for any reason (median 11, IQR 5 to 21.75) than the general population (median 1, IQR 0 to 4) and had a higher healthcare burden than controls with type 1 diabetes or type 2 diabetes (all p<0.001). Indigenous individuals were over-represented in the cohort (n=358; 14.8% vs 1.5% of the general population) and had higher healthcare utilisation than other patients with CP (p<0.001).

CP is a significant burden on the SA healthcare system and was more prevalent and more burdensome in Indigenous adults. CP consumes a disproportionate level of public health services. Our findings support further research and preventive efforts, particularly in the Indigenous population.

This review provides a comprehensive update on the diagnostic approaches to chronic pancreatitis (CP), emphasizing recent advancements in imaging techniques, biomarker research, and multivariable scoring systems. Despite substantial progress in these areas, current diagnostic algorithms have limitations, particularly for early and non-calcific CP. Traditional criteria have focused on classic diagnostic signs, but "minimal change" CP is increasingly recognized through advanced imaging and function tests. This article aims to guide clinicians in applying current methods and available strategies for CP diagnosis and outline research efforts in the field.

Pain is the foremost complication of chronic pancreatitis (CP), affecting about 70% of patients. However, the pathophysiological understanding and management of CP-related pain are complex, likely as patients have diverse "pain phenotypes" responding differently to treatment. This study aims to develop a bedside test panel to identify distinct pain phenotypes, investigate the temporal evolution, and determine whether they can be used to predict treatment response.

The INPAIN study is an international, multicenter, observational, longitudinal cohort study consisted of 4 substudies. The studies will prospectively enroll 400 CP patients (50 without pain and 350 with pain) and 50 control subjects, conducting biannual observations for 4 years. The test panel is consisted of comprehensive subjective and objective assessment parameters. Statistical analysis strategies differ across the substudies. A model to predict treatment efficacy will be developed using various machine learning techniques, including an artificial intelligence approach, with internal cross-validation. Trajectories in pain parameters will be characterized by graphical analysis and mixed effect models.

The INPAIN study aims to comprehensively understand pain in CP through a test panel developed for routine clinical use. This tool has the potential to personalize treatments, improve clinical practice, enhance patient care, improve quality of life, and minimize treatment side effects.

Pancreatic atrophy is commonly observed in end-stage chronic pancreatitis (CP). Diagnostic standards for pancreatic atrophy not well established. The present cross-sectional observation study explored two-point pancreatic size measurements in a large CP cohort from the Scandinavian Baltic Pancreatic Club (SBPC) database to validate clinically relevant cutoffs for pancreatic atrophy and explore associations to etiological factors and disease outcomes.

Patients with CP according to M-ANNHEIM diagnostic criteria were included. We measured maximal axial dimension of the pancreatic head and body and recorded presence of calcifications and pancreatic duct changes on cross-sectional imaging. We calculated cutoffs for clinically relevant atrophy related to exocrine pancreatic dysfunction (EPD) defined as fecal elastase (FE) < 200. Associations between pancreatic atrophy and smoke, alcohol, sex, body size and disease outcomes were analysed using multivariate logistic regression.

We included 539 CP patients (356 male) from four centres in the SBPC study group. Small pancreatic size represented by sum of two-point maximal axial dimension less than 31 mm for females and 37.5 mm for males predicted EPD with good specificity (males: 0.89 (95 % CI, 0.81, 0.95), females: 0.96 (95 % CI, 0.85, 0.99)) but poor sensitivity (males: 0.38 (95 % CI, 0.31, 0.45), females 0.25 (95 % CI, 0.18, 0.35). Male sex, increasing age and long duration of CP were clearly associated with pancreatic atrophy. Corrected for other factors reducing exocrine capacity, pancreatic atrophy was still strongly associated to EPD.

We conclude that following the suggested cutoffs, pancreatic atrophy in CP is independently associated with EPD.

Acute on chronic pancreatitis(ACP) is a common cause of treatment in patients with chronic pancreatitis(CP). However, as far as we know, research on ACP has been few, and the quality may vary. This study intended to explore the risk factors related to acute exacerbation in patients with chronic pancreatitis.

313 patients with CP were analyzed based on clinical data from 2014 to 2023 and categorized into ACP and non-ACP groups. Their data, assessed across eleven parameters, were used to study risk variables associated with acute exacerbation in patients with chronic pancreatitis.

Of the 313 eligible patients, 163(52.1%) were ACP. Age > 50 years old (P = 0.049, OR = 0.614, 95%CI: 0.378-0.998), recurrent acute pancreatitis(RAP) history (P = 0.000, OR = 3.284, 95%CI: 1.972-5.467) and steatorrhea (P = 0.013, OR = 0.189, 95%CI: 0.051-0.704) were related factors for ACP.

The history of RAP was an independent risk factor for ACP. Age and steatosis were protective of the prevalence of ACP.

Tailoring surgical treatment is mandatory to optimize outcomes in chronic pancreatitis. Total pancreatectomy (TP) offers pain relief in a subset of patients. TP with islet autotransplantation (IAT) has the potential to reduce the burden of postsurgical diabetes. We present the first Scandinavian prospective study assessing outcomes following total pancreatectomy and islet autotransplantation (TPIAT) in chronic pancreatitis. Our aim was to assess short- and long-term outcomes following implementation of a nationwide program of TPIAT at a tertiary reference center for pancreatic surgery in Norway.

A prospective, observational single-center study enrolling consecutive patients undergoing TPIAT for chronic pancreatitis at Oslo University Hospital. The selection of potential candidates for TPIAT was based on discussions at multidisciplinary team (MDT) meetings, focusing on tailored surgery in chronic pancreatitis. Patients were finally evaluated in a dedicated TPIAT team. The outcome measures included pain relief, quality of life (QoL) assessed by EORTC QLQ-C30, complications, and glycemic control.

Between August 2017 and November 2022, 15 patients underwent TPIAT. The follow-up rate was 87% with a median follow-up of 26 months (range = 14-65). Pain relief was achieved in 92%. EORTC QLQ-C30 analysis revealed clinically significant improvements in 28 of 30 domains, particularly in pain and role- and social-functioning. The Clavien-Dindo ≥IIIa complications occurred in one patient. There was no 90 days mortality. All patients maintained C-peptide positivity, although none of the patients reached insulin independence.

TPIAT was as a safe and effective treatment for a selected group of patients with chronic pancreatitis, providing substantial pain relief and enhanced QoL. Islet autotransplantation prevented complete insulin deficiency, reducing diabetes severity postpancreatectomy. Dedicated chronic pancreatitis MDT meetings were key factor in the success of the program.

Background: The role of diet on the risk of chronic pancreatitis (CP) is understudied. The health benefits of the Mediterranean diet (MedDiet) pattern have long been recognized, but its association with CP risk is unclear. We aimed to investigate the association between adherence to MedDiet and the incidence of CP in a large-scale cohort. Methods: 190 790 participants from the UK Biobank were involved, all free of CP and with typical diet recall data at recruitment. The diagnosis of CP was ascertained by the combination of hospital inpatient data, primary care data, and death registry data. Multivariable Cox regression models were used to evaluate the associations between MedDiet adherence, measured by the Mediterranean Diet Adherence Screener (MEDAS) continuous score, and the incidence of CP. The mediating role of inflammation (assessed by C-reactive protein) and metabolic status between MedDiet adherence and CP risk was also investigated. Results: During a mean of 10.8 years of follow-up, 214 participants developed CP. Individuals with the highest adherence to MedDiet, defined by continuous MEDAS scores, exhibited significantly lower risk of developing CP (hazard ratio [HR] = 0.57, 95% confidence interval [CI]: 0.40-0.82; p = 0.002) compared to those in the lowest tertiles. Metabolic status mediated 4.74% of the association between MedDiet adherence and CP risk, while the mediating role of C-reactive protein was not significant. Conclusion: Greater Mediterranean diet adherence is associated with reduced chronic pancreatitis risk.

Opioids used to manage severe pain in acute pancreatitis (AP) might exacerbate the disease through effects on gastrointestinal and immune functions. Methylnaltrexone, a peripherally acting µ-opioid receptor antagonist, may counteract these effects without changing analgesia.

This double-blind, randomized, placebo-controlled trial included adult patients with AP and systemic inflammatory response syndrome at 4 Danish centers. Patients were randomized to receive 5 days of continuous intravenous methylnaltrexone (0.15 mg/kg/d) or placebo added to the standard of care. The primary end point was the Pancreatitis Activity Scoring System score after 48 hours of treatment. Main secondary outcomes included pain scores, opioid use, disease severity, and mortality.

In total, 105 patients (54% men) were randomized to methylnaltrexone (n = 51) or placebo (n = 54). After 48 hours, the Pancreatitis Activity Scoring System score was 134.3 points in the methylnaltrexone group and 130.5 points in the placebo group (difference 3.8, 95% confidence interval [CI] -40.1 to 47.6; P = 0.87). At 48 hours, we found no differences between the groups in pain severity (0.0, 95% CI -0.8 to 0.9; P = 0.94), pain interference (-0.3, 95% CI -1.4 to 0.8; P = 0.55), and morphine equivalent doses (6.5 mg, 95% CI -2.1 to 15.2; P = 0.14). Methylnaltrexone also did not affect the risk of severe disease (8%, 95% CI -11 to 28; P = 0.38) and mortality (6%, 95% CI -1 to 12; P = 0.11). The medication was well tolerated.

Methylnaltrexone treatment did not achieve superiority over placebo for reducing the severity of AP.

Spinal cord stimulation (SCS) has emerged as a treatment option for patients with chronic pancreatitis (CP) who experience pain that does not respond to standard interventions. However, there is a lack of sham-controlled trials to support its efficacy.

This randomized, double-blinded, sham-controlled, cross-over trial enrolled 16 CP patients with insufficient pain relief from standard therapies. Patients underwent high-frequency (1000 Hz) paraesthesia-free SCS or sham for two 10-day stimulation periods, separated by a 3-day washout period. The primary outcome was daily pain intensity registered in a pain diary based on a numeric rating scale (NRS). Secondary outcomes included various questionnaires. Quantitative sensory testing was used to probe the pain system before and after interventions.

The average daily pain score on the NRS at baseline was 5.2 ± 1.9. After SCS, the pain score was 4.2 ± 2.1 compared to 4.3 ± 2.1 in the sham group (mean difference -0.1, 95% CI [-1.4 to 1.1]; P = 0.81). Similarly, no differences were observed between groups for the maximal daily pain score, secondary outcomes or quantitative sensory testing parameters. During an open-label, non-sham-controlled and non-blinded extension of the study, the average daily NRS was 5.2 ± 1.7 at baseline, 3.2 ± 1.8 at 3 months, 2.9 ± 1.9 at 6 months and 3.4 ± 2.2 at 12 months of follow-up (P = 0.001).

In this first sham-controlled trial of SCS in painful CP, we did not find evidence of short-term pain relief with paraesthesia-free high-frequency (1000 Hz) stimulation. However, evaluation of the long-term effect by larger sham-controlled trials with long-term follow-up is warranted.

In this first sham-controlled trial to apply high-frequency (1000 Hz) spinal cord stimulation in patients with visceral pain due to chronic pancreatitis, we did not find evidence for clinically relevant pain relief. Taken together with potential procedure-related complications, adverse effects and costs associated with spinal cord stimulation, our findings question its use for management of visceral pain.

Alcohol and nicotine are the two most important risk factors of chronic pancreatitis, and they often occur together. It is still unclear how much they influence the severity of the disease and which of the two addictions should be treated with priority.

We performed a single-center, retrospective, cross-sectional study in a mixed medicosurgical cohort of 870 patients diagnosed with chronic pancreatitis (CP). We analyzed the impact of the drinking pattern and abstinence for alcohol and nicotine on the course of the disease. Patients with alcoholic CP were subdivided into 1) patients with "life-time drinking history" (LTDH), 2) "current drinkers" with current alcohol abuse without signs of LTDH, and 3) "former drinkers" who stopped or reduced alcohol intake dramatically.

Compared to patients with LTDH, "former drinkers" had a lower rate of exocrine insufficiency (29% vs. 59%) and pseudocysts (33% vs. 49%), were more often relapse-free (37% vs. 5%), and had less abdominal pain. There was no correlation detected between the quantity of alcohol consumption and the severity or progression of the disease. Regarding nicotine, 29 pack-years are the threshold for developing the early stage of CP. Under nicotine abstinence, only slightly more patients were relapse-free (37% vs. 22%). In contrast, the cumulative amount of nicotine consumed correlated with overall disease severity and the development of pseudocysts. The need for surgery was increased, with odds ratios of 1.8, for both alcohol and nicotine abuse.

Alcohol cessation in chronic pancreatitis reduces exocrine insufficiency, abdominal pain, and local complications. The effect of nicotine cessation is less pronounced in our cohort. However, nicotine abuse represents an important factor for the development of the disease.

Endoscopic ultrasound (EUS) is the most sensitive method for diagnosing chronic pancreatitis (CP) in its early stages, and Rosemont Classification (RC) is used for its evaluation. Data on the correlation between EUS features and pancreatic exocrine insufficiency (PEI) are limited. We investigated the correlation between the EUS findings and PEI.

This was a retrospective, monocentric cohort study involving patients prospectively enrolled from 2018 to 2022, with definite or probable CP according to the M-ANNHEIM criteria. All the patients underwent EUS and exocrine function investigations within 12 months of diagnosis. PEI was diagnosed using fecal elastase (FE) or when overt steatorrhea was reversed by pancreatic enzyme replacement therapy. Logistic regression analyses, rank correlation, ROC curve, and area under the curve (AUROC) were performed to evaluate the association between EUS features and PEI, and the accuracy of RC in predicting PEI.

Among 128 patients examined (63.3 % male; mean age, 47 years), 69.5 % were diagnosed with PEI. In multivariate logistic regression among all the RC criteria, only lithiasis in the main pancreatic duct (MPD) was associated with increased risk of PEI (OR 2.92, 95 % CI 1.29-6.61; p = 0.01). Rank analysis showed a weak inverse correlation between RC and FE (Spearman's rho = -0.02; p = 0.03). The accuracy of RC was moderate (AUROC 0.62, p = 0.014).

Among RC EUS features, lithiasis in the MPD is helpful for predicting the risk of PEI, while other findings are of limited utility in evaluating exocrine function.

Refractory pain is a major clinical problem in patients with pancreatic ductal adenocarcinoma (PDAC) and chronic pancreatitis (CP). New, effective therapies to reduce pain are urgently needed. Intravenous lidocaine is used in clinical practice in patients with PDAC and CP, but its efficacy has not been studied prospectively.

Multicenter prospective nonrandomized pilot study included patients with moderate or severe pain (Numeric Rating Scale ≥ 4) associated with PDAC or CP in 5 Dutch centers. An intravenous lidocaine bolus of 1.5 mg/kg was followed by continuous infusion at 1.5 mg/kg/hr. The dose was raised every 15 minutes until treatment response (up to a maximum 2 mg/kg/hr) and consecutively administered for 2 hours. Primary outcome was the mean difference in pain severity, preinfusion, and the first day after (Brief Pain Inventory [BPI] scale 1-10). A BPI decrease ≥1.3 points was considered clinically relevant.

Overall, 30 patients were included, 19 with PDAC (63%) and 11 with CP (37%). The mean difference in BPI at day 1 was 1.1 (SD ± 1.3) points for patients with PDAC and 0.5 (SD ± 1.7) for patients with CP. A clinically relevant decrease in BPI on day 1 was reported in 9 of 29 patients (31%), and this response lasted up to 1 month. No serious complications were reported, and only 3 minor complications (vertigo, nausea, and tingling of mouth). Treatment with lidocaine did not impact quality of life.

Intravenous lidocaine in patients with painful PDAC and CP did not show an overall clinically relevant reduction of pain. However, this pilot study shows that the treatment is feasible in this patient group and had a positive effect in a third of patients which lasted up to a month with only minor side effects. To prove or exclude the efficacy of intravenous lidocaine, the study should be performed in a study with a greater sample size and less heterogeneous patient group.

The European Pancreatic Club Lifetime Achievement Award is a distinction awarded for research on the pancreas and service to European Pancreatology. It comes with the obligation to submit a review article to our society's journal, Pancreatology. It was awarded to me 2023 and I take this opportunity to highlight my journey with the central organ AKA the pancreas, that is inseparatable from "Pancreas 2000" - an educational program for future pancreatologists, inaugurated by Karolinska Institutet.

Retinoids participate in multiple key processes in the human body e.g., vision, cell differentiation and embryonic development. There is growing evidence of the relationship between retinol, its active metabolite- all-trans retinoic acid (ATRA) - and several pancreatic disorders. Although low levels of ATRA in pancreatic ductal adenocarcinoma (PDAC) tissue have been reported, data on serum levels of ATRA in PDAC is still limited. The aim of our work was to determine serum concentrations of retinol and ATRA in patients with PDAC, type-2 diabetes mellitus (T2DM), chronic pancreatitis (CHP) and healthy controls.

High performance liquid chromatography with UV detection (HPLC) was used to measure serum levels of retinol and ATRA in 246 patients with different stages of PDAC, T2DM, CHP and healthy controls.

We found a significant decrease in the retinol concentration in PDAC (0.44+/-0.18 mg/L) compared to T2DM (0.65+/-0.19 mg/L, P<0.001), CHP (0.60+/-0.18 mg/L, P< 0.001) and healthy controls (0.61+/-0.15 mg/L, P<0.001), significant decrease of ATRA levels in PDAC (1.14+/-0.49 ug/L) compared to T2DM (1.37+/-0.56 ug/L, P<0.001) and healthy controls(1.43+/-0.55 ug/L, P<0.001). Differences between early stages (I+II) of PDAC and non-carcinoma groups were not significant. We describe correlations between retinol, prealbumin and transferrin, and correlation of ATRA and IGFBP-2.

Significant decrease in retinol and ATRA levels in PDAC compared to T2DM, healthy individuals and/or CHP supports existing evidence of the role of retinoids in PDAC. However, neither ATRA nor retinol are suitable for detection of early PDAC. Correlation of ATRA levels and IGFBP-2 provides new information about a possible IGF and retinol relationship.

Extracorporeal shock wave lithotripsy (ESWL) is used for the treatment of pancreatic duct stones (PDS) in patients with chronic pancreatitis (CP). We aimed to develop a CT based index to predict the required number of ESWL sessions for technical success.

We retrospectively evaluated patients with PDS secondary to CP who underwent ESWL. Technical success was defined as the complete fragmentation of stones to <3 mm. CT features including PDS size, number, location, and density in Hounsfield units (HU) were noted. We analyzed the relationship between PDS characteristics and the number of ESWL sessions required for technical success. A multiple linear regression model was used to combine size and density into the pancreatic duct stone (PDS) index that was translated into a web-based calculator.

There were 206 subjects (mean age 38.6 ± 13.7 years, 59.2% male) who underwent ESWL. PDS size showed a moderate correlation with the number of ESWL sessions (r = 0.42, p < 0.01). PDS in the head required a fewer number of sessions in comparison to those in the body (1.4 ± 0.6 vs. 1.6 ± 0.7, p = 0.01). There was a strong correlation between PDS density and the number of ESWL sessions (r = 0.617, p-value <0.01). The PDS index {0.3793 + [0.0009755 x PDS density (HU)] + [0.02549 x PDS size (mm)]} could accurately predict the required number of ESWL sessions with an AUC of 0.872 (p < 0.01).

The PDS index is a useful predictor of the number of ESWL sessions needed for technical success that can help in planning and patient counseling.

Surgical drainage for chronic pancreatitis patients with a normal-sized pancreatic head remains controversial. Both Frey and extended Partington procedures could be used, but the level of evidence is weak.

The object of this prospective cohort study was to assess the mid-term results concerning pain, quality of life, and pancreatic function of surgical drainage (Frey or extended Partington procedure) in patients with painful chronic pancreatitis and a normal-sized pancreatic head.

Fifty-nine patients (Frey procedure: 14 cases; extended Partington procedure: 45 cases) were enrolled in the study with a median length of follow-up of 16 months. The effective and complete pain relief rate was 85% and 58%, respectively. The Izbicki score decreased from 53.4 preoperatively to 8.8 postoperatively. The general 12-Item Short Form Health Survey (SF-12) score increased from 45.2 to 75.4. The pancreatic insufficiency did not change significantly postoperatively. At three months after surgery, the complete pain relief and Izbicki score were more favorable in the Frey group than in the extended Partington group.

Both Frey and extended Partington procedures resulted in excellent pain relief and quality of life improvement and did not worsen pancreatic function. The Frey procedure could yield a more favorable result in the early postoperative period.

Data on the incidence and clinical relevance of gallstones in patients with suspected acute alcoholic pancreatitis are lacking and are essential to minimize the risk of recurrent acute pancreatitis. The aim of this study was to assess the incidence of gallstones and the associated rate of recurrent acute pancreatitis in patients with presumed acute alcoholic pancreatitis.

Between 2008 and 2019, 23 hospitals prospectively enrolled patients with acute pancreatitis. Those diagnosed with their first episode of presumed acute alcoholic pancreatitis were included in this study. The term gallstones was used to describe the presence of cholelithiasis or biliary sludge found during imaging. The primary outcome was pancreatitis recurrence during 3 years of follow-up.

A total of 334 patients were eligible for inclusion, of whom 316 were included in the follow-up analysis. Gallstone evaluation, either during the index admission or during follow-up, was performed for 306 of 334 patients (91.6%). Gallstones were detected in 54 patients (17.6%), with a median time to detection of 6 (interquartile range 0-42) weeks. During follow-up, recurrent acute pancreatitis occurred in 121 of 316 patients (38.3%), with a significantly higher incidence rate for patients with gallstones compared with patients without gallstones (59% versus 34.2% respectively; P < 0.001), while more patients with gallstones had stopped drinking alcohol at the time of their first recurrence (41% versus 24% respectively; P = 0.020). Cholecystectomy was performed for 19 patients with gallstones (36%). The recurrence rate was lower for patients in the cholecystectomy group compared with patients who did receive inadequate treatment or no treatment (5/19 versus 19/34 respectively; P = 0.038).

Gallstones were found in almost one in every five patients diagnosed with acute alcoholic pancreatitis. Gallstones were associated with a higher rate of recurrent pancreatitis, while undergoing cholecystectomy was associated with a reduction in this rate.

Psychiatric comorbidity measured by screening instruments is common in patients with chronic pancreatitis (CP) but whether this accurately reflects clinical diagnosis of psychiatric comorbidity is unknown and the prevalence of psychotropic medication prescription in CP remains largely unexplored.

Adult patients (≥18 years) with definite CP were enrolled and completed the Hospital Anxiety and Depression Scale (HADS). Demographics, clinical characteristics and medications were retrieved from case report forms and the electronic health record (EHR). Clinical diagnosis of depression or anxiety was determined by presence of ICD-10 code or inclusion in the patient's EHR problem list or treatment plan. Comparisons were made between patients with and without clinical psychiatric comorbidity.

Total of 81 patients (48, 59.3% male; mean age 57.6 ± 14.3 years) were included. Clinical diagnoses of anxiety and depression were each noted in 47 (58%) patients, with overlap in 42 (51.9%). Compared to clinical diagnoses, the sensitivity and specificity of a positive screen for anxiety (HADS >7) were 76.6% and 91.2%; for depression 55.3% and 88.2%. Patients with anxiety and/or depression were more frequently female (51.9% v 20.7%), younger (53.6 v 64.9 years), and had alcohol etiology (51.9% v 27.6%) (all p < 0.01). In those with psychiatric comorbidity, 42 (80.8%) were prescribed psychotropic medication, most commonly gabapentinoid (24, 57.1%), selective serotonin reuptake inhibitor (n = 22, 52.4%) or benzodiazepine (n = 20, 47.6%).

Psychiatric comorbidities are common among CP patients and many receive psychotropic medications. Further studies are needed to evaluate the impact of these medications on CP symptoms.

Background and Objectives: The pancreas, ensconced within the abdominal cavity, requires a plethora of sophisticated imaging modalities for its comprehensive evaluation, with ultrasonography serving as a primary investigative technique. A myriad of pancreatic pathologies, encompassing pancreatic neoplasia and a spectrum of inflammatory diseases, are detectable through these imaging strategies. Nevertheless, the intricate anatomical confluence and the pancreas's deep-seated topography render the visualization and accurate diagnosis of its pathologies a formidable endeavor. The objective of our paper is to review the best diagnostic imagistic tools for the pancreas. Materials and Methods: we have gathered several articles using Prisma guidelines to determine the best imagistic methods. The imperative of pancreatic scanning transcends its diagnostic utility, proving to be a pivotal element in a multitude of clinical specialties, notably surgical oncology. Within this domain, multidetector computed tomography (MDCT) of the pancreas holds the distinction of being the paramount imaging modality, endorsed for its unrivaled capacity to delineate the staging and progression of pancreatic carcinoma. In synergy with MDCT, there has been a notable advent of avant-garde imaging techniques in recent years. These advanced methodologies, including ultrasonography, endoscopic ultrasonography, contrast-enhanced ultrasonography, and magnetic resonance imaging (MRI) conjoined with magnetic resonance cholangiopancreatography (MRCP), have broadened the horizon of tumor characterization, offering unparalleled depth and precision in oncological assessment. Other emerging diagnostic techniques, such as elastography, also hold a lot of potential and promise for the future of pancreatic imaging. Fine needle aspiration (FNA) is a quick, minimally invasive procedure to evaluate lumps using a thin needle to extract tissue for analysis. It is less invasive than surgical biopsies and usually performed as an outpatient with quick recovery. Its accuracy depends on sample quality, and the risks include minimal bleeding or discomfort. Results, guiding further treatment, are typically available within a week. Elastography is a non-invasive medical imaging technique that maps the elastic properties and stiffness of soft tissue. This method, often used in conjunction with ultrasound or MRI, helps differentiate between hard and soft areas in tissue, providing valuable diagnostic information. It is particularly useful for assessing liver fibrosis, thyroid nodules, breast lumps, and musculoskeletal conditions. The technique is painless and involves applying gentle pressure to the area being examined. The resulting images show tissue stiffness, indicating potential abnormalities. Elastography is advantageous for its ability to detect diseases in early stages and monitor treatment effectiveness. The procedure is quick, safe, and requires no special preparation, with results typically available immediately. Results: The assembled and gathered data shows the efficacy of various techniques in discerning the nature and extent of neoplastic lesions within the pancreas. Conclusions: The most common imaging modalities currently used in diagnosing pancreatic neoplasms are multidetector computed tomography (MDCT), endoscopic ultrasound (EUS), and magnetic resonance imaging (MRI), alongside new technologies, such as elastography.

More insight into the incidence of and factors associated with progression following a first episode of acute pancreatitis (AP) would offer opportunities for improvements in disease management and patient counseling.

A long-term post hoc analysis of a prospective cohort of patients with AP (2008-2015) was performed. Primary endpoints were recurrent acute pancreatitis (RAP), chronic pancreatitis (CP), and pancreatic cancer. Cumulative incidence calculations and risk analyses were performed.

Overall, 1184 patients with a median follow-up of 9 years (IQR: 7-11) were included. RAP and CP occurred in 301 patients (25%) and 72 patients (6%), with the highest incidences observed for alcoholic pancreatitis (40% and 22%). Pancreatic cancer was diagnosed in 14 patients (1%). Predictive factors for RAP were alcoholic and idiopathic pancreatitis (OR 2.70, 95% CI 1.51-4.82 and OR 2.06, 95% CI 1.40-3.02), and no pancreatic interventions (OR 1.82, 95% CI 1.10-3.01). Non-biliary etiology (alcohol: OR 5.24, 95% CI 1.94-14.16, idiopathic: OR 4.57, 95% CI 2.05-10.16, and other: OR 2.97, 95% CI 1.11-7.94), RAP (OR 4.93, 95% CI 2.84-8.58), prior pancreatic interventions (OR 3.10, 95% CI 1.20-8.02), smoking (OR 2.33, 95% CI 1.14-4.78), and male sex (OR 2.06, 95% CI 1.05-4.05) were independently associated with CP.

Disease progression was observed in a quarter of pancreatitis patients. We identified several risk factors that may be helpful to devise personalized strategies with the intention to reduce the impact of disease progression in patients with AP.