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.

This study sought to clarify the utility of T2-weighted imaging (T2WI)-based radiomics to predict the recurrence of acute pancreatitis (AP) in subjects with metabolic syndrome (MetS).

Data from 196 patients with both AP and MetS from our hospital were retrospectively analyzed. These patients were separated into two groups according to their clinical follow-up outcomes, including those with first-onset AP (n = 114) and those with recurrent AP (RAP) (n = 82). The 196 cases were randomly divided into a training set (n = 137) and a test set (n = 59) at a 7:3 ratio. The clinical characteristics of these patients were systematically compiled for further analysis. For each case, the pancreatic parenchyma was manually delineated slice by slice using 3D Slicer software, and the appropriate radiomics characteristics were retrieved. The K-best approach, the least absolute shrinkage and selection operator (LASSO) algorithm, and variance thresholding were all used in the feature selection process. The establishment of clinical, radiomics, and combined models for forecasting AP recurrence in patients with MetS was then done using a random forest classifier. Model performance was measured using the area under the receiver operating characteristic curve (AUC), and model comparison was done using the DeLong test. The clinical utility of these models was evaluated using decision curve analysis (DCA), and the optimal model was determined via a calibration curve.

In the training set, the clinical, radiomics, and combined models yielded respective AUCs of 0.651, 0.825, and 0.883, with corresponding test sets of AUCs of 0.606, 0.776, and 0.878. Both the radiomics and combined models exhibited superior predictive effectiveness compared to the clinical model in both the training (p = 0.001, p < 0.001) and test sets (p = 0.04, p < 0.001). The combined model outperformed the radiomics model (training set: p = 0.025, test set: p = 0.019). The DCA demonstrated that the radiomics and combined models had greater clinical efficacy than the clinical model. The calibration curve for the combined model demonstrated good agreement between the predicted probability of AP recurrence and the observed outcomes.

These findings highlight the superior predictive power of a T2WI-based radiomics model for predicting AP recurrence in patients with MetS, potentially supporting early interventions that can mitigate or alleviate RAP.

Acute pancreatitis, recurrent acute pancreatitis, and chronic pancreatitis are recognized as a continuum of pancreatic diseases. Recurrence increases the risk of progression to chronic pancreatitis. The aim of this study was to search for clinical features that may promote the progression of chronic pancreatitis in patients with recurrent acute pancreatitis.

We retrospectively reviewed patients with recurrent acute pancreatitis from Medical Information Mart for Intensive Care-IV database. They were divided into a training cohort and a validation cohort. A nomogram was constructed based on clinical features during the second hospitalization. The discrimination and calibration of the nomogram were evaluated using the concordance index, area under the time-dependent receiver operating characteristic curve, and calibration plots.

A total of 432 recurrent acute pancreatitis patients were evaluated, of which 93 (21.53%) were diagnosed with chronic pancreatitis later. Age, biliary pancreatitis, admission interval, alcohol dependence, lipase, and platelet were selected. The concordance index was 0.717 (95% confidence interval: 0.691-0.743) for the training cohort and 0.718 (95% confidence interval: 0.662-0.774) for the validation cohort. The area under the time-dependent receiver operating characteristic curve was >0.7 over 1000 days.

A nomogram was developed and validated to evaluate the transition from recurrent acute pancreatitis to chronic pancreatitis.

Recurrent acute pancreatitis (RAP) is a complex syndrome that presents variably, with many cases remaining idiopathic after thorough diagnostics. For evaluating structural etiologies, endoscopic ultrasound and MR cholangiopancreatography are preferred over endoscopic retrograde cholangiopancreatography (ERCP) given their more favorable risk profile and sensitivity. The diagnostic work-up remains paramount since treatment should focus on addressing underlying causes such as early cholecystectomy for gallstone pancreatitis. As more etiologic factors are uncovered, such as genetic susceptibility, causality becomes more nuanced. Earlier enthusiasm for endoscopic sphincterotomy as a treatment for idiopathic RAP has been tempered by less favorable studies in recent years.

Cellular and gene therapy (CGT) products have emerged as a popular approach in regenerative medicine, showing promise in treating various pancreatic and liver diseases in numerous clinical trials. Before these therapies can be tested in human clinical trials, it is essential to evaluate their safety and efficacy in relevant animal models. Such preclinical testing is often required to obtain regulatory approval for investigational new drugs. However, there is a lack of detailed guidance on selecting appropriate animal models for CGT therapies targeting specific pancreatic and liver conditions, such as pancreatitis and chronic liver diseases. In this review, the gastrointestinal committee for the International Society for Cell and Gene Therapy provides a summary of current recommendations for animal species and disease model selection, as outlined by the US Food and Drug Administration, with references to EU EMA and Japan PMDA. We discuss a range of small and large animal models, as well as humanized models, that are suitable for preclinical testing of CGT products aimed at treating pancreatic and liver diseases. For each model, we cover the associated pathophysiology, commonly used metrics for assessing disease status, the pros and limitations of the models, and the relevance of these models to human conditions. We also summarize the use and application of humanized mouse and other animal models in evaluating the safety and efficacy of CGT products. This review aims to provide comprehensive guidance for selecting appropriate animal species and models to help bridge the gap between the preclinical research and clinical trials using CGT therapies for specific pancreatic and liver diseases.

Percutaneous cholecystostomy (PC) can be used as a bridging therapy for moderately severe acute biliary pancreatitis (MSABP). Currently, there are only a limited number of reports of MSABP using PCs.

To assess the short-term outcomes of early PC in MSABP and factors associated with recurrence and death in MSABP.

Patients who received conservative treatment or PC for acute biliary pancreatitis (ABP) in Liaoning Provincial People's Hospital from January 2017 to July 2022 were collected. A total of 54 patients with MSABP who received early-stage PC and 29 patients who received conservative treatment. The short-term efficacy of PC was evaluated. Depending on whether there is a recurrence, compare the characteristics of the pre-PC and explore the factors of recurrence. Pre-PC features were compared and predictors were discussed, depending on the outcome.

After 3 days of PC treatment, patients experienced a reduction in inflammatory markers compared to the conservative group. After PC, patients were divided into non-recurrence (n = 37) and recurrence (n = 10) groups, and the results showed that age was an independent correlation affecting ABP recurrence [odds ratio (OR) = 0.937, 95% confidence interval (CI): 0.878-0.999; P = 0.047 < 0.05]. Patient outcomes were divided into non-lethal (n = 47) and lethal (n = 7) groups, and Charlson Comorbidity Index (CCI) was a risk factor for mortality (OR = 2.397, 95%CI: 1.139-5.047; P = 0.021 < 0.05). CCI was highly accurate in predicting death in MSABP (area under the curve = 0.86 > 0.7). When the Youden index maximum was 0.565, the cut-off value was 5.5, the sensitivity was 71.4%, and the specificity was 85.1%.

PC is an important method in the early years (< 72 hours) of MSABP. Age is a protective factor against recurrence of ABP. High pre-PC CCI is significantly associated with mortality.

This case report aims to enhance understanding of pancreatobiliary maljunction (PBM) and promote more proactive treatment.

The patient, a 24-year-old Chinese female, was admitted to the hospital on April 7, 2020, due to "recurrent abdominal pain for over 2 years, with a recent episode accompanied by nausea and vomiting for 1 day." She had a previous history of gallstones.

The initial diagnosis upon admission was biliary acute pancreatitis. During the emergency endoscopic retrograde cholangiopancreatography (ERCP) procedure, anatomical abnormalities were discovered. Intraoperative endoscopic ultrasonography led to a diagnosis of complex PBM (JSPBM, type D) + choledochal cyst (Todani, Ic) + incomplete pancreatic divisum + early chronic pancreatitis. These diagnoses were confirmed by postoperative magnetic resonance cholangiopancreatography.

After multiple conservative treatments such as ERCP with accessory pancreatic duct stent placement, the patient underwent surgical treatment in April 2021, which included "laparoscopic left hemihepatectomy + choledochal cyst excision + cholecystectomy + hepatic portal cholangioplasty."

The patient has not experienced any abdominal pain since the surgery and is currently under regular follow-up.

Endoscopic ultrasound is effective for the diagnoses of complex PBM and incomplete pancreatic divisum. ERCP with pancreatic duct stent placement and surgical procedure is reliable for relieving the patient's symptoms.

Recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP) lack effective therapies. There is no consensus or guidance on which endpoints or outcome measures should be used in clinical trials. This study aimed to develop a core outcome set aligned with both patient and provider priorities for RAP and CP. Utilizing the Outcomes Measures in Rheumatology (OMERACT) framework, a multi-stakeholder approach was adopted to identify and prioritize outcome domains.

A two-round Delphi poll was conducted among four stakeholder groups: adult patients, parents and pediatric patients, adult health care providers and pediatric health care providers. Steering committee consensus further refined the core outcome domains, categorizing them as mandatory, important but optional, or research agenda domains, with full consensus achieved.

Pain severity, ability to participate in social roles and activities, pancreatitis related hospitalization/ER visits and acute pancreatitis flare-ups were recommended as mandatory outcome domains for future clinical trials in RAP/CP.

Using the OMERACT framework, we developed a core outcome set for RAP and CP. Future research will focus on identifying validated measures for each domain, facilitating standardized assessments across clinical trials.

The acute and chronic pancreatitis (CP) can lead to severe complications like walled-off necrosis, large symptomatic pseudocyst or multiorgan failure. The treatment of these complications is multivariate and can differ from conservative, symptomatic treatment or minimal-invasive, endoscopic transgastral stenting to transgastral necrosectomy.

This study aims to analyse the clinical course for patients that develop local complications of severe pancreatitis.

This is a retrospective observational single-centre study on 46 patients with severe pancreatitis.

In this retrospective single-centre study, 46 out of 474 inpatients from January 2014 to December 2020, who were treated because of an acute or CP, developed acute pancreatitis complications and could be included. We analysed and compared the clinical course of different treatments (lumen apposing metal stents, transgastral double pigtail stent, endoscopic retrograde cholangiopancreatography, operation, conservative treatment) and different complications (walled-off necrosis (WON), pancreatic pseudocyst (PPC)).

Forty-six patients developed an acute complication due to severe pancreatitis. Twenty-seven patients developed a WON, while 19 patients suffered from PPC. 48% of the whole cohort had an alcoholic aetiology of pancreatitis. 78% were treated with antibiotics, 48% suffered from infected pancreatitis and 22% needed intensive care treatment. WON patients more often had a longer hospitalization of more than 21 days. PPC patients were correlated with an alcoholic aetiology, whereas WON patients were inversely correlated with an alcoholic aetiology. Increased lactate dehydrogenase, lipase, and C-reactive protein levels as well as leucocyte count could be associated with a higher probability to exhibit a WON instead of another local complication. The mortality rate was low with 7% in our study.

WON and PPC differ in certain patients and laboratory characteristics such as aetiology, elevated laboratory values, antibiotic treatment or the duration of hospitalization. Invasive treatment is not required in all severe pancreatitis cases.

Pancreatitis is a common, life-threatening inflammatory disease of the exocrine pancreas. Its pathogenesis remains obscure, and no specific or effective treatment is available. Gallstones and alcohol excess are major etiologies of pancreatitis; in a small portion of patients the disease is hereditary. Pancreatitis is believed to be initiated by injured acinar cells (the main exocrine pancreas cell type), leading to parenchymal necrosis and local and systemic inflammation. The primary function of these cells is to produce, store, and secrete a variety of enzymes that break down all categories of nutrients. Most digestive enzymes, including all proteases, are secreted by acinar cells as inactive proforms (zymogens) and in physiological conditions are only activated when reaching the intestine. The generation of trypsin from inactive trypsinogen in the intestine plays a critical role in physiological activation of other zymogens. It was proposed that pancreatitis results from proteolytic autodigestion of the gland, mediated by premature/inappropriate trypsinogen activation within acinar cells. The intra-acinar trypsinogen activation is observed in experimental models of acute and chronic pancreatitis, and in human disease. On the basis of these observations, it has been considered the central pathogenic mechanism of pancreatitis - a concept with a century-old history. This review summarizes the data on trypsinogen activation in experimental and genetic rodent models of pancreatitis, particularly the more recent genetically engineered mouse models that mimic mutations associated with hereditary pancreatitis; analyzes the mechanisms mediating trypsinogen activation and protecting the pancreas against its' damaging effects; discusses the gaps in our knowledge, potential therapeutic approaches, and directions for future research. We conclude that trypsin is not the culprit in the disease pathogenesis but, at most, a mediator of some pancreatitis responses. Therefore, the search for effective therapies should focus on approaches to prevent or normalize other intra-acinar pathologic processes, such as defective autophagy leading to parenchymal cell death and unrelenting inflammation.

The purpose of this review is to provide a practical guide for the clinical care of patients with acute pancreatitis (AP) from the management of the early phases of disease to the treatment of local complications. AP is one of the most frequent causes of gastroenterological admission in emergency departments. It is characterized by a dynamic and unpredictable course and in its most severe forms, is associated with organ dysfunction and/or local complications, requiring intensive care with significant morbidity and mortality. Initial therapy includes adequate fluid resuscitation, nutrition, analgesia, and when necessary critical care support. In recent years, the development of minimally invasive tailored treatments for local complications, such as endoscopic drainage, has improved patients' acceptance and outcomes. Despite this, the management of AP remains a challenge for clinicians. The present review was conducted by the authors, who formulated specific questions addressing the most critical and current aspects of the clinical course of AP with the aim of providing key messages.

Patients with chronic illnesses are susceptible to the financial burden of disease-related treatment costs. Financial toxicity is well researched in cancer and several chronic diseases. This review explores the financial challenges faced by patients with chronic pancreatitis and the impact of financial hardship on their well-being.

We performed a review of the published literature to summarize the body of existing research and to identify knowledge gaps related to the financial burden experienced by patients with chronic pancreatitis.

Research on financial burden, cost-coping behaviors, cost-related nonadherence to prescribed medications, and social vulnerabilities in people with chronic pancreatitis is sparse. No studies have assessed the suitability and validity of instruments measuring subjective financial toxicity in a patient population with chronic pancreatitis.

There is a critical need for further studies of financial toxicity in the patient population with chronic pancreatitis, considering that if the sources of financial burden can be identified, opportunities emerge to dampen or mitigate their impact on patients with chronic pancreatitis.

Acute pancreatitis (AP) is a leading cause of emergency hospitalization. We present the current diagnostic and therapeutic status of AP as revealed by analysis of a large multicenter dataset.

The medical records of patients diagnosed with AP between 2018 and 2019 in 12 tertiary medical centers in Korea were retrospectively reviewed.

In total, 676 patients were included, of whom 388 (57.4%) were male, and the mean age of all patients was 58.6 years. There were 355 (52.5%), 301 (44.5%), and 20 (3.0%) patients with mild, moderate, and severe AP, respectively, as assessed by the revised Atlanta classification. The most common etiologies of AP were biliary issues (41.6%) and alcohol consumption (24.6%), followed by hypertriglyceridemia (6.8%). The etiology was not identified in 111 (16.4%) patients at the time of initial admission. The overall mortality rate was 3.3%, increasing up to 45.0% among patients with severe AP. Notably, 70.0% (14/20) of patients with severe AP and 81.5% (154/189) of patients with systemic inflammatory response syndrome had received <4 L per day during the initial 24 hours of admission. Only 23.8% (67/281) of acute biliary pancreatitis patients underwent cholecystectomy during their initial admission. In total, 17.8% of patients experienced recurrent attacks during follow-up. However, none of the patients with acute biliary pancreatitis experienced recurrent attacks if they had undergone cholecystectomy during their initial admission.

This study provides insights into the current status of AP in Korea, including its etiology, severity, and management. Results reveal disparities between clinical guidelines and their practical implementation for AP treatment.

This narrative review addresses idiopathic acute pancreatitis (IAP) and its epidemiology, diagnosis, clinical course and treatment during the last decade. As there is no previously validated protocol for finding the aetiology of acute pancreatitis (AP), the primary aim of this study is to find, describe and unify evidence about the diagnostic work-up of AP to diagnose the true IAP. By finding the aetiology with the highest possible yield it may be possible to reduce recurrent AP (RAP) episodes and related morbidity and thereby decrease health care costs and possibly improve patients' quality of life.

This narrative review includes articles retrieved from PubMed search with publications from 2013-2023. Cross references were used when found relevant.

The rates of aetiologies of AP and the diagnostics performed behind these numbers vary widely between different studies, time periods and different geographical regions, as there is no unified algorithm in diagnostic work-up of IAP. In this study, we describe an up-to-date summary of epidemiology, diagnostic course and treatment of IAP, and propose an algorithm of IAP diagnostics in light of recent scientific studies and their outcomes and address possible treatments of IAP.

Although aetiology is key for AP management, there is still no validated protocol for aetiological diagnosis. IAP is relevant due to its recurrence rate and possible evolution to chronic pancreatitis. We still need more studies addressing this topic and evaluating new diagnostic protocols with advanced tests and treatment strategies in true IAP.

The purpose of this study was to investigate the risk of metabolic sequelae and all-cause mortality in a population-based cohort of chronic pancreatitis (CP) patients with and without prior acute pancreatitis (AP).

We used nationwide health registries to identify all Danish residents (18 years and older) with incident CP from 2000 to 2018. Information on AP/CP diagnoses, metabolic sequelae (post-pancreatitis diabetes mellitus [PPDM], exocrine pancreatic dysfunction, and osteoporosis), and all-cause mortality were obtained from Danish national health registries. CP cases were stratified based on the presence of AP before CP diagnosis. The risk of metabolic sequelae and all-cause mortality was expressed as hazard ratios (HRs) with 95% confidence intervals (CIs), calculated using multivariate Cox proportional hazards models.

A total of 9,655 patients with CP were included. Among patients with CP, 3,913 (40.5%) had a prior AP diagnosis. Compared with patients without a history of AP, patients with prior AP had a decreased risk of death (HR 0.79, 95% CI 0.74-0.84), which was largely confined to the initial period after CP diagnosis. Patients with prior AP had an increased risk of PPDM (HR 1.53, 95% CI 1.38-1.69), which persisted for up to a decade after CP diagnosis. No overall differences in risk were observed for exocrine pancreatic dysfunction (HR 0.97, 95% CI 0.87-1.07) and osteoporosis (HR 0.87, 95% CI 0.74-1.02).

This nationwide study revealed that most of the patients with CP have no prior episode(s) of AP, indicating that an attack of AP sensitizing the pancreas is not essential for CP development. CP patients with and without prior AP have different risk profiles of PPDM and all-cause mortality.

Acute pancreatitis (AP) is a common gastrointestinal disease with high morbidity and mortality rate. Unfortunately, neither the etiology nor the pathophysiology of AP are fully understood and causal treatment options are not available. Recently we demonstrated that heparanase (Hpa) is adversely involved in the pathogenesis of AP and inhibition of this enzyme ameliorates the manifestation of the disease. Moreover, a pioneer study demonstrated that Aspirin has partial inhibitory effect on Hpa. Another compound, which possesses a mild pancreato-protective effect against AP, is Trehalose, a common disaccharide. We hypothesized that combination of Aspirin, Trehalose, PG545 (Pixatimod) and SST0001 (Roneparstat), specific inhibitors of Hpa, may exert pancreato-protective effect better than each drug alone. Thus, the current study examines the pancreato-protective effects of Aspirin, Trehalose, PG545 and SST0001 in experimental model of AP induced by cerulein in wild-type (WT) and Hpa over-expressing (Hpa-Tg) mice. Cerulein-induced AP in WT mice was associated with significant rises in the serum levels of lipase (X4) and amylase (X3) with enhancement of pancreatic edema index, inflammatory response, and autophagy. Responses to cerulein were all more profound in Hpa-Tg mice versus WT mice, evident by X7 and X5 folds increase in lipase and amylase levels, respectively. Treatment with Aspirin or Trehalose alone and even more so in combination with PG545 or SST0001 were highly effective, restoring the serum level of lipase back to the basal level. Importantly, a novel newly synthesized compound termed Aspirlose effectively ameliorated the pathogenesis of AP as a single agent. Collectively, the results strongly indicate that targeting Hpa by using anti-Hpa drug combinations constitute a novel therapy for this common orphan disease.

Chronic pancreatitis (CP) in young individuals may lead to disease-related secondary sarcopenia (SSARC), characterized by muscle loss and systemic inflammation. In this study, CP was induced in young pigs, and serum levels of key hormones, muscle fiber diameters in various muscles, and the mRNA expression of genes related to oxidative stress and programmed cell death were assessed. A decrease in muscle fiber diameters was observed in SSARC pigs, particularly in the longissimus and diaphragm muscles. Hormonal analysis revealed alterations in dehydroepiandrosterone, testosterone, oxytocin, myostatin, and cortisol levels, indicating a distinct hormonal response in SSARC pigs compared to controls. Oxytocin levels in SSARC pigs were significantly lower and myostatin levels higher. Additionally, changes in the expression of catalase (CAT), caspase 8 (CASP8), B-cell lymphoma 2 (BCL2), and BCL2-associated X protein (BAX) mRNA suggested a downregulation of oxidative stress response and apoptosis regulation. A reduced BAX/BCL2 ratio in SSARC pigs implied potential caspase-independent cell death pathways. The findings highlight the complex interplay between hormonal changes and muscle degradation in SSARC, underscoring the need for further research into the apoptotic and inflammatory pathways involved in muscle changes due to chronic organ inflammation in young individuals.

Chronic pancreatitis (CP) is a progressive inflammatory disorder associated with marked morbidity and mortality and frequently requires hospitalization. This study aimed to investigate the time trends and geographical distribution of hospital admissions, the lethality rate of CP across Brazil, and the potential relationship with social indicators and associated risk factors.

Data were retrospectively obtained from the Brazilian Public Health System Registry between January 2009 and December 2019. The prevalence and lethality rates of CP per 100,000 inhabitants in each municipality were estimated from hospitalizations to in-hospital deaths and classified by age, sex, and demographic features.

During the study period, 64,609 admissions were retrieved, and most of the patients were males (63.54%). Hospitalization decreased by nearly half (-54.68%) in both sexes. CP rates in males were higher in all age groups. The greatest reduction in admissions (- 64%) was also noted in patients ≥ 70y. CP In-hospital lethality remained stable (5-6%) and similar for males and females. Patients ≥ 70y showed the highest lethality. The greatest increase in CP lethality rates (+ 10%) was observed in municipalities integrated into metropolises, which was mainly driven by small-sized municipalities (+ 124%).

CP hospitalizations decrease in both urban and rural areas, particularly in the North, Northeast, and Central-West regions, and in those above 70 years of age, but are not correlated with lethality rates in the South. This suggests ongoing changes in the environmental and socioeconomic factors in Brazil.

Chronic pancreatitis (CP) is a progressive inflammatory disease with an increasing global prevalence. In recent years, a strong association between CP and metabolic bone diseases (MBDs), especially osteoporosis, has been identified, attracting significant attention in the research field. Epidemiological data suggest a rising trend in the incidence of MBDs among CP patients. Notably, recent studies have highlighted a profound interplay between CP and altered nutritional and immune profiles, offering insights into its linkage with MBDs. At the molecular level, CP introduces a series of biochemical disturbances that compromise bone homeostasis. One critical observation is the disrupted metabolism of vitamin D and vitamin K, both essential micronutrients for maintaining bone integrity, in CP patients. In this review, we provide physio-pathological perspectives on the development and mechanisms of CP-related MBDs. We also outline some of the latest therapeutic strategies for treating patients with CP-associated MBDs, including stem cell transplantation, monoclonal antibodies, and probiotic therapy. In summary, CP-associated MBDs represent a rising medical challenge, involving multiple tissues and organs, complex disease mechanisms, and diverse treatment approaches. More in-depth studies are required to understand the complex interplay between CP and MBDs to facilitate the development of more specific and effective therapeutic approaches.

Acute pancreatitis (AP) is one of the most common gastrointestinal tract diseases with significant morbidity and mortality. Current treatments remain unspecific and supportive due to the severity and clinical course of AP, which can fluctuate rapidly and unpredictably. Mitochondria, cellular power plant to produce energy, are involved in a variety of physiological or pathological activities in human body. There is a growing evidence indicating that mitochondria damage-associated molecular patterns (mtDAMPs) play an important role in pathogenesis and progression of AP. With the pro-inflammatory properties, released mtDAMPs may damage pancreatic cells by binding with receptors, activating downstream molecules and releasing inflammatory factors. This review focuses on the possible interaction between AP and mtDAMPs, which include cytochrome c (Cyt c), mitochondrial transcription factor A (TFAM), mitochondrial DNA (mtDNA), cardiolipin (CL), adenosine triphosphate (ATP) and succinate, with focus on experimental research and potential therapeutic targets in clinical practice. Preventing or diminishing the release of mtDAMPs or targeting the mtDAMPs receptors might have a role in AP progression.

HPSE2, the gene-encoding heparanase 2 (Hpa2), is mutated in urofacial syndrome (UFS), a rare autosomal recessive congenital disease attributed to peripheral neuropathy. Hpa2 lacks intrinsic heparan sulfate (HS)-degrading activity, the hallmark of heparanase (Hpa1), yet it exhibits a high affinity toward HS, thereby inhibiting Hpa1 enzymatic activity. Hpa2 regulates selected genes that promote normal differentiation, tissue homeostasis, and endoplasmic reticulum (ER) stress, resulting in antitumor, antiangiogenic, and anti-inflammatory effects. Importantly, stress conditions induce the expression of Hpa2, thus establishing a feedback loop, where Hpa2 enhances ER stress which, in turn, induces Hpa2 expression. In most cases, cancer patients who retain high levels of Hpa2 survive longer than patients bearing Hpa2-low tumors. Experimentally, overexpression of Hpa2 attenuates the growth of tumor xenografts, whereas Hpa2 gene silencing results in aggressive tumors. Studies applying conditional Hpa2 knockout (cHpa2-KO) mice revealed an essential involvement of Hpa2 contributed by the host in protecting against cancer and inflammation. This was best reflected by the distorted morphology of the Hpa2-null pancreas, including massive infiltration of immune cells, acinar to adipocyte trans-differentiation, and acinar to ductal metaplasia. Moreover, orthotopic inoculation of pancreatic ductal adenocarcinoma (PDAC) cells into the pancreas of Hpa2-null vs. wild-type mice yielded tumors that were by far more aggressive. Likewise, intravenous inoculation of cancer cells into cHpa2-KO mice resulted in a dramatically increased lung colonization reflecting the involvement of Hpa2 in restricting the formation of a premetastatic niche. Elucidating Hpa2 structure-activity-relationships is expected to support the development of Hpa2-based therapies against cancer and inflammation.

To investigate profiles of circulating immune signatures in healthy controls and chronic pancreatitis patients (CP) with and without a preceding history of acute pancreatitis (AP).

We performed a phase 1, cross-sectional analysis of prospectively collected serum samples from the PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translation StuDies (PROCEED) study. All samples were collected during a clinically quiescent phase. CP subjects were categorized into two subgroups based on preceding episode(s) of AP. Healthy controls were included for comparison. Blinded samples were analyzed using an 80-plex Luminex assay of cytokines, chemokines, and adhesion molecules. Group and pairwise comparisons of analytes were performed between the subgroups.

In total, 133 patients with CP (111 with AP and 22 without AP) and 50 healthy controls were included. Among the 80 analytes studied, CP patients with a history of AP had significantly higher serum levels of pro-inflammatory cytokines (interleukin (IL)-6, IL-8, IL-1 receptor antagonist, IL-15) and chemokines (Cutaneous T-Cell Attracting Chemokine (CTACK), Monokine induced Gamma Interferon (MIG), Macrophage-derived Chemokine (MDC), Monocyte Chemoattractant Protein-1 (MCP-1)) compared to CP without preceding AP and controls. In contrast, CP patients without AP had immune profiles characterized by low systemic inflammation and downregulation of anti-inflammatory mediators, including IL-10.

CP patients with a preceding history of AP have signs of systemic inflammatory activity even during a clinically quiescent phase. In contrast, CP patients without a history of AP have low systemic inflammatory activity. These findings suggest the presence of two immunologically diverse subtypes of CP.

To investigate scoring systems and biomarkers for determining the severity and prognosis of acute pancreatitis (AP). Between January and July 2023, 100 patients with AP diagnosed and treated in the emergency department were included. AP was divided into 2 groups according to severity: mild AP and moderately severe AP (MSAP-SAP), according to the revised Atlanta Classification in 2012. Demographic characteristics, severity, intensive care unit (ICU) admission, white blood cell count (WBC), hematocrit, red cell distribution width from whole blood taken at admission and 48 hours later, C-reactive protein (CRP) and biochemistry values, Bedside Index for Severity in Acute Pancreatitis (BISAP), Pancreatitis Activity Scoring System (PASS), and harmless AP score scores were recorded retrospectively. Our variables, which were found to be significant in multiple logistic regression results, were found to increase MSAP-SAP expectation by 4.36-, 7.85-, 6.63 and 5.80 times in the presence of CRP > 47.10, WBC > 13.10, PASS > 0, and necrotizing computed tomography findings, respectively. It was detected that the risk factor which was found significant as a single variable affecting the ICU admission increased the risk of ICU requirement by 28.88 when PASS > 0, by 3.96 when BISAP > 1, and it increased the Atlanta score by 9.93-fold. We found that WBC and CRP values at the time of hospital admission and WBC, CRP, and red cell distribution width values after 48 had the highest accuracy in determining AP disease severity. BISAP, which was found to be significant in determining MSAP-SAP expectations, lost its significance in multiple logistic regression results, and PASS was found to be effective. The PASS is an important score in the clinical evaluation of patients with AP and in determining the need for ICU hospitalization.

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.

Traditional Chinese Medicine (TCM) is a unique medical system of historic significance, holding substantial influence within China and beyond. In recent years, the efficacy of TCM in treating acute pancreatitis has been substantiated. Despite over two decades of development in this domain, a bibliometric analysis illustrating TCM's role in acute pancreatitis remains scarce.

This study aims to conduct a comprehensive analysis of findings in the field of acute pancreatitis and TCM using machine learning and text-analyzing methodologies. The intent is to provide scientific and intuitive support to researchers and clinicians.

We searched the Web of Science Core Collection database for publications and related literature from 2007 to mid-2023. Tools such as Excel, Citespace V, and Vosviewer were utilized for bibliometric analysis. That included assessing published and cited counts, co-authorship mapping, co-citation analysis, burst detection, and keyword analysis.

The study revealed a fluctuating growth trend in the number of publications and citations since 2007. As many as 147 institutions from 13 countries, with a total of 756 authors, have published 202 papers in 76 academic journals. Sichuan University in China and Tang Wenfu have been recognized as the most influential national institution and author. The most frequently published journal is "Pancreas", while the most cited is the "World Journal of Gastroenterology". Commonly used single herbs in this field include Baicalin, Emodin, Rhubarb, and Salvia miltiorrhizae. Frequently used herbal formulations include Da chengqi decoction, Chaiqin chengqi decoction, and Qing yi decoction. Current research hotspots primarily surround concepts like hmgb1, nf-kappab, nfr2, oxidative stress, exosomes, nlrp3, pyroptosis, etc. Potential future research themes could relate to pharmacology, reducing hmgb1, inflammatory response, cell activation, Qing Yi-decoction, etc. This review holds significant guiding importance for clinical and scientific research into TCM treatment for acute pancreatitis in the future.

Patients who have survive a burn injury might be at risk of opioid dependence after discharge. This study examined the use of opioids in patients who suffer burn injury and explored factors associated with persistent opioid use after hospital discharge.

This retrospective cohort study compared adults admitted with a burn injury from 2009 to 2019 with two matched comparison cohorts from the general population and adults with a diagnosis of acute pancreatitis. Pre-admission prescription opioid use was determined, and a multivariable negative binomial regression analysis used to explore post-discharge opioid use.

A total of 7147 burn patients were matched with 6810 pancreatitis patients and with 28 184 individuals from the general population. Pre-admission opioid use was higher in the burn and pancreatitis cohorts (29% and 40%, respectively) compared with the general population (17%). Opioid use increased in both burn and pancreatitis cohorts after discharge (41% and 53%, respectively), although patients with pancreatitis were at even higher risk of increased opioid use in an adjusted analysis (incidence rate ratio 1.43). Female sex, lower socioeconomic status, ICU admission, pre-injury opioid use, and a history of excess alcohol use were all associated with an increase in opioid prescriptions after discharge.

Opioid use is high in those admitted with a burn injury or acute pancreatitis when compared with the general population, increasing further after hospital discharge. Female sex and socioeconomic deprivation are among factors that make increased opioid use more likely, although this phenomenon seems even more pronounced in those with acute pancreatitis compared with burn injuries.

Recurrent acute pancreatitis is beginning to be recognized as an intermediary stage in the continuous spectrum between acute and chronic pancreatitis. It is crucial to identify this disease stage and intervene with diagnostic and therapeutic modalities to prevent the painful and irreversible condition of chronic pancreatitis. We review the recent advances in diagnosing and managing this important 'call for action' condition.

This systematic review evaluates the efficacy of surgical interventions in improving the quality of life for patients with chronic pancreatitis (CP). A thorough literature search, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, identified 11 studies that focused on patient-reported outcomes after surgical treatments, including pancreatic resections, drainage procedures, and duodenum-preserving head resections. The findings indicate that organ-preserving procedures, notably the Frey and Beger operations, significantly enhance pain control and overall quality of life while reducing analgesic dependency. This review provides crucial insights into the long-term efficacy and comparative benefits of different surgical approaches, highlighting the need for personalized surgical strategies in CP management. It emphasizes the necessity for standardized outcome measures and further comparative research to refine CP treatment protocols.

Patients with chronic pancreatitis (CP) often have severe and intractable abdominal pain, leading to decreased quality of life (QOL), inability to work or attend school, and increased health care costs due to repeated emergency room visits and hospitalizations.

We evaluated the efficacy of total pancreatectomy and islet autotransplantation (TPIAT) in terms of pain control and QOL in CP patients treated at our center in Japan. To evaluate QOL, we used the Short-Form 36 Health Survey version 2 (SF-36v2® Standard, Japanese), European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), and Quality of Life Questionnaire-Pancreatic Modification (QLQ-PAN28).

Between August 2016 and June 2019, we performed this procedure in 5 patients. All patients were followed up for 12 months and all transplanted islets were still functioning at the 1-year follow-up. The major adverse events were abdominal wall hemorrhage, intestinal obstruction, intra-abdominal abscess, and abdominal pain requiring hospitalization; no case had sequelae. No major complications were due to islet transplantation. Pain scores improved postoperatively in all patients. Three QOL item dimensions role-physical (p = 0.03125), general health perception (p = 0.03125) and vitality (p = 0.03125) in the SF-36 were significantly improved 12 months after TPIAT. Mean values of many other QOL items improved, though not significantly.

The QOL improvement after TPIAT for CP suggests its effectiveness in the Japanese population.

Understanding the nature of inflammatory pancreatic diseases is essential for planning health care system requirements and interventions. The aim of this study was to quantify the trajectories of inflammatory pancreatic diseases and their association with pancreatic cancer in a population-based setting.

National health registries were used to identify all Danish residents (18 years or older) in the period from 2000 through 2018 with incident cases of acute pancreatitis (AP), recurrent acute pancreatitis (RAP), chronic pancreatitis (CP), and pancreatic cancer. We used a multistate model to examine transitions from a healthy state to intermediate states of acute pancreatic inflammation (AP and RAP) to chronic states (CP and pancreatic cancer) and, ultimately, death. Results were reported as transition incidence rates per 1000 person-years with 95% CIs.

There were 4,663,864 individuals included (mean age, 46 years; 51% were women). During a mean follow-up of 16.8 years, 31,396 individuals were diagnosed with incident AP, 5546 with RAP, 8898 with CP, and 18,182 with pancreatic cancer. The cumulative incidence of pancreatitis (acute and chronic) during the study period was 0.80% (95% CI, 0.79%-0.80%). The transition incidence rates to CP were 12.1 (95% CI, 8.1-18.1) from AP, 46.8 (95% CI, 31.6-69.3) from RAP, and 0.07 (95% CI, 0.04-0.13) from a healthy state. Similar patterns were observed for transitions to pancreatic cancer. Most patients diagnosed with CP (64.2%) and pancreatic cancer (96.4%) transitioned directly from a healthy state. Among patients with pancreatitis, 41.0% (95% CI, 40.5%-41.5%) died during follow-up.

The study findings revealed an increased risk of CP and pancreatic cancer in patients with a history of AP. However, most patients with CP and pancreatic cancer transitioned directly from a healthy state.

The rarity of lipodystrophies implies that they are not well-known, leading to delays in diagnosis/misdiagnosis. The aim of this study was to assess the natural course and comorbidities of generalised and partial lipodystrophy in Spain to contribute to their understanding. Thus, a total of 140 patients were evaluated (77.1% with partial lipodystrophy and 22.9% with generalised lipodystrophy). Clinical data were collected in a longitudinal setting with a median follow-up of 4.7 (0.5-17.6) years. Anthropometry and body composition studies were carried out and analytical parameters were also recorded. The estimated prevalence of all lipodystrophies in Spain, excluding Köbberling syndrome, was 2.78 cases/million. The onset of phenotype occurred during childhood in generalised lipodystrophy and during adolescence-adulthood in partial lipodystrophy, with the delay in diagnosis being considerable for both cohorts. There are specific clinical findings that should be highlighted as useful features to take into account when making the differential diagnosis of these disorders. Patients with generalised lipodystrophy were found to develop their first metabolic abnormalities sooner and a different lipid profile has also been observed. Mean time to death was 83.8 ± 2.5 years, being shorter among patients with generalised lipodystrophy. These results provide an initial point of comparison for ongoing prospective studies such as the ECLip Registry study.

To investigate the correlation between anthropometric indexes [cardiometabolic index (CMI), lipid accumulation products (LAP), waist triglyceride index (WTI), and body mass index (BMI)] and acute pancreatitis (AP) in a Chinese adult population.

The present investigation consisted of a prospective group including 117,326 subjects who were enrolled in the Kailuan investigation. The individuals were categorized into quartiles based on their baseline levels of CMI, LAP, and WIT. BMI was categorized into three distinctive groups: normal weight group (BMI < 24 kg/m2), overweight group (BMI 24-28 kg /m2), and obesity group (BMI ≥ 28 kg/m2). The data were subjected to analysis in order to investigate the correlation between these anthropometric indexes and the incidence of AP. Cox regression models were employed to assess the relative risk of AP while accounting for known risk factors through appropriate adjustments.

Over the course of a median follow-up duration of 12.59 ± 0.98 years, we documented 401 incident AP cases. Incidence density and cumulative incidence rates of AP increased with the increase of CMI, LAP, and WTI. After multivariate adjustment, the fourth quartile of CMI, LAP, and WTI exhibited the greatest risk of AP [CMI: hazard ratio (HR) 1.93, 95% confidential interval (CI) (1.45-2.57); LAP: HR 2.00, 95% CI(1.49-2.68); WTI: HR 2.13,95% CI (1.59-2.83)]. In comparison to the normal weight group, the obesity group (BMI ≥ 28 kg/m2) had an elevated risk of AP (HR = 1.58, 95% CI: 1.21-2.05). Furthermore, the incremental effect of BMI combined with CMI on the prognostic value of AP was greater than that of BMI alone (the C statistics demonstrated a result of 0.607 versus 0.546; the integrated discrimination improvement revealed a result of 0.321%; net reclassification improvement was 1.975%).

We found that CMI, LAP, and WTI were positively and independently connected to the risk of AP. Additionally, CMI demonstrates a superior prognostic capacity than other indexes in anticipating AP.

We aimed to evaluate the incidence and risk of pancreatic cancer (PC) in pancreatitis. We identified patients with acute pancreatitis (AP) (n = 225,811, 50.0%) and chronic pancreatitis (CP) (n = 225,685, 50.0%) from Korean population-based data and matched them with age- and sex-matched controls (n = 4,514,960). We analyzed the incidence and adjusted hazard ratios (aHRs) of PC among patients followed for more than 2 years or 5 years, and assessed risk changes over time in single episode of AP (SAP), recurrent AP (RAP), CP with AP, and CP without AP groups. We also performed subgroup analysis for both sexes. The incidences (per 104 person-years) and risks (aHR) of PC were higher in the RAP (12.69, 5.00) or CP with AP (12.12, 5.74) groups compared to the SAP (2.31, 1.32) or CP without AP (2.28, 1.57) groups. The risks of PC decreased over time, however, the risk of PC remained elevated in the RAP and CP with AP groups for more than 8 years. Females with RAP, SAP, and CP with AP had higher risks of PC than males. The risk of PC is higher and persists for longer duration in patients with RAP and CP with AP compared to those with SAP or CP without AP.

Acute pancreatitis is a common and serious inflammatory condition currently lacking disease modifying therapy. The cholinergic anti-inflammatory pathway (CAP) is a potent protective anti-inflammatory response activated by vagus nerve-dependent α7 nicotinic acetylcholine receptor (α7nAChR) signaling using splenic CD4+ T cells as an intermediate. Activating the CAP ameliorates experimental acute pancreatitis. Galantamine is an acetylcholinesterase inhibitor (AChEI) which amplifies the CAP via modulation of central muscarinic ACh receptors (mAChRs). However, as mAChRs also activate pancreatitis, it is currently unknown whether galantamine would be beneficial in acute pancreatitis.

The effect of galantamine (1-6 mg/kg-body weight) on caerulein-induced acute pancreatitis was evaluated in mice. Two hours following 6 hourly doses of caerulein (50 µg/kg-body weight), organ and serum analyses were performed with accompanying pancreatic histology. Experiments utilizing vagotomy, gene knock out (KO) technology and the use of nAChR antagonists were also performed.

Galantamine attenuated pancreatic histologic injury which was mirrored by a reduction in serum amylase and pancreatic inflammatory cytokines and an increase the anti-inflammatory cytokine IL-10 in the serum. These beneficial effects were not altered by bilateral subdiaphragmatic vagotomy, KO of either choline acetyltransferase+ T cells or α7nAChR, or administration of the nAChR ganglionic blocker mecamylamine or the more selective α7nAChR antagonist methyllycaconitine.

Galantamine improves acute pancreatitis via a mechanism which does not involve previously established physiological and molecular components of the CAP. As galantamine is an approved drug in widespread clinical use with an excellent safety record, our findings are of interest for further evaluating the potential benefits of this drug in patients with acute pancreatitis.

Recurrent acute pancreatitis poses a significant challenge in clinical management. In this case, a young, obese woman with metabolic syndrome presented with her third episode of acute pancreatitis within a span of 4 months. Due to unavailability, plasmapheresis could not be performed, and the patient was managed solely with pharmacological therapy. Initial evaluation revealed abdominal pain, tenderness and elevated laboratory markers. CT scan findings indicated pancreatic and peripancreatic oedema. Further investigations highlighted the presence of hypertriglyceridaemia and hypocalcaemia. As the patient was using oral contraceptive pills (OCP), it was crucial to consider their potential role in causing hypertriglyceridaemia. Consequently, the patient was advised to discontinue OCP use. Despite the lack of plasmapheresis, intensive medical management, including medication and lifestyle modifications, showed positive results. This case underscores the importance of recognising the association between OCP, hypertriglyceridaemia and recurrent pancreatitis in patients with metabolic syndrome.