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INTRODUCTION: Chronic Pancreatitis Prognosis Score (COPPS) was developed to discriminate disease severity and predict risk for future hospitalizations. In this cohort study, we evaluated if COPPS predicts the likelihood of hospitalization(s) in an American cohort. METHODS: The CPDPC consortium provided data and serum from subjects with chronic pancreatitis (N=279). COPPS was calculated with baseline data and stratified by severity (low, moderate, high). Primary endpoints included number and duration of hospitalizations during 12-month follow-up. RESULTS: The mean±SD COPPS was 8.4±1.6. COPPS correlated with all primary outcomes: hospitalizations for any reason (number: r=0.15, p=0.01; duration: r=0.16, p=0.01) and pancreas-related hospitalizations (number: r=0.15, p=0.02; duration: r=0.13, p=0.04). The severity distribution was 13.3% low, 66.0% moderate, and 20.8% high. 37.6% of subjects had ≥1 hospitalization(s) for any reason; 32.2% had ≥1 pancreas-related hospitalization(s). All primary outcomes were significantly different between severity groups: hospitalizations for any reason (number, p=0.004; duration, p=0.007) and pancreas-related hospitalizations (number, p=0.02; duration, p=0.04). The prevalence of continued drinking at follow-up (p=0.04) was higher in the low and moderate groups. The prevalence of anxiety at enrollment (p=0.02) and follow-up (p<0.05) was higher in the moderate and high groups. DISCUSSION: Statistically, COPPS significantly correlated with hospitalization outcomes, but the correlations were weaker than in previous studies, which may be related to the outpatient nature of the PROCEED cohort and lower prevalence of high severity disease. Studies in other prospective cohorts are needed to understand the full utility of COPPS as a potential tool for clinical risk assessment and intervention.
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Acute pancreatitis (AP), defined as acute inflammation of the pancreas, is one of the most common diseases of the gastrointestinal tract leading to hospital admission in the United States. It is important for clinicians to appreciate that AP is heterogenous, progressing differently among patients and is often unpredictable. While most patients experience symptoms lasting a few days, almost one-fifth of patients will go on to experience complications, including pancreatic necrosis and/or organ failure, at times requiring prolonged hospitalization, intensive care, and radiologic, surgical, and/or endoscopic intervention. Early management is essential to identify and treat patients with AP to prevent complications. Patients with biliary pancreatitis typically will require surgery to prevent recurrent disease and may need early endoscopic retrograde cholangiopancreatography if the disease is complicated by cholangitis. Nutrition plays an important role in treating patients with AP. The safety of early refeeding and importance in preventing complications from AP are addressed. This guideline will provide an evidence-based practical approach to the management of patients with AP.
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Pancreatite , Humanos , Pancreatite/terapia , Pancreatite/etiologia , Pancreatite/diagnóstico , Doença Aguda , Colangiopancreatografia Retrógrada Endoscópica , Estados UnidosRESUMO
BACKGROUND AND AIMS: Although pancreatic endotherapy (PET) is commonly used for treating adverse events of chronic pancreatitis, data on the frequency and factors associated with the use of PET are limited. Our aim was to define the use of and factors predictive for receiving PET in a well-characterized chronic pancreatitis cohort. METHODS: This is a cross-sectional analysis of data from PROCEED, a multicenter U.S. cohort study of chronic pancreatitis. PET modalities primarily consisted of ERCP. A treatment course was defined as the number of sessions performed for a specific indication. A repeat course was defined as PET >1 year after completion of the last course. Multivariable logistic regression identified predictive factors for receiving PET, and proportional rates model assessed risk factors for repeat PET. RESULTS: Of 681 subjects, 238 (34.9%) received PET. Factors associated with receiving PET included female sex (odds ratio [OR], 1.26; 95% confidence interval [CI], 1.03-1.53), lower education (OR, 1.30; 95% CI, 1.04-1.62), income ≤$50,000 per year (OR, 1.35; 95% CI, 1.07-1.71), and prior acute pancreatitis (OR, 1.74; 95% CI, 1.31-2.32). Of 238 subjects, 103 (43.3%) underwent repeat PET at a median duration of 2 years, with 23.1% receiving 2 courses, 9.7% receiving 3 courses, and 10.4% receiving ≥4 courses. CONCLUSIONS: Nearly half of patients with chronic pancreatitis who undergo PET received 1 or more repeat courses within 2 to 3 years. In addition to a prior history of acute pancreatitis, demographic and socioeconomic factors were associated with receiving PET.
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Colangiopancreatografia Retrógrada Endoscópica , Pancreatite Crônica , Humanos , Pancreatite Crônica/terapia , Feminino , Masculino , Pessoa de Meia-Idade , Estados Unidos , Estudos Transversais , Adulto , Fatores Sexuais , Estudos de Coortes , Idoso , Modelos Logísticos , Escolaridade , Renda , Fatores de Risco , Retratamento/estatística & dados numéricos , Análise MultivariadaRESUMO
BACKGROUND: Chronic abdominal pain is the hallmark symptom of chronic pancreatitis (CP), with 50% to 80% of patients seeking medical attention for pain control. Although several management options are available, outcomes are often disappointing, and opioids remain a mainstay of therapy. Opioid-induced hyperalgesia is a phenomenon resulting in dose escalation, which may occur partly because of the effects of opioids on voltage-gated sodium channels associated with pain. Preclinical observations demonstrate that the combination of an opioid and the antiseizure drug lacosamide diminishes opioid-induced hyperalgesia and improves pain control. OBJECTIVE: In this phase 1 trial, we aim to determine the safety, tolerability, and dose-limiting toxicity of adding lacosamide to opioids for the treatment of painful CP and assess the feasibility of performance of a pilot study of adding lacosamide to opioid therapy in patients with CP. As an exploratory aim, we will assess the efficacy of adding lacosamide to opioid therapy in patients with painful CP. METHODS: Using the Bayesian optimal interval design, we will conduct a dose-escalation trial of adding lacosamide to opioid therapy in patients with painful CP enrolled in cohorts of size 3. The initial dose will be 50 mg taken orally twice a day, followed by incremental increases to a maximum dose of 400 mg/day, with lacosamide administered for 7 days at each dose level. Adverse events will be documented according to Common Terminology Criteria for Adverse Events (version 5.0). RESULTS: As of December 2023, we have currently enrolled 6 participants. The minimum number of participants to be enrolled is 12 with a maximum of 24. We expect to publish the results by March 2025. CONCLUSIONS: This trial will test the feasibility of the study design and provide reassurance regarding the tolerability and safety of opioids in treating painful CP. It is anticipated that lacosamide will prove to be safe and well tolerated, supporting a subsequent phase 2 trial assessing the efficacy of lacosamide+opioid therapy in patients with painful CP, and that lacosamide combined with opiates will lower the opioid dose necessary for pain relief and improve the safety profile of opioid use in treating painful CP. TRIAL REGISTRATION: Clinicaltrials.gov NCT05603702; https://clinicaltrials.gov/study/NCT05603702. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/50513.
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OBJECTIVE: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.
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Citocinas , Pancreatite Crônica , Humanos , Projetos Piloto , Doença Aguda , Estudos Transversais , Quimiocinas , Interleucina-6RESUMO
BACKGROUND: The management of acute necrotizing pancreatitis (ANP) has changed dramatically over the past 20 years including the use of less invasive techniques, the timing of interventions, nutritional management, and antimicrobial management. This study sought to create a core outcome set (COS) to help shape future research by establishing a minimal set of essential outcomes that will facilitate future comparisons and pooling of data while minimizing reporting bias. METHODS: A modified Delphi process was performed through involvement of ANP content experts. Each expert proposed a list of outcomes for consideration, and the panel anonymously scored the outcomes on a 9-point Likert scale. Core outcome consensus defined a priori as >70% of scores receiving 7 to 9 points and <15% of scores receiving 1 to 3 points. Feedback and aggregate data were shared between rounds with interclass correlation trends used to determine the end of the study. RESULTS: A total of 19 experts agreed to participate in the study with 16 (84%) participating through study completion. Forty-three outcomes were initially considered with 16 reaching consensuses after four rounds of the modified Delphi process. The final COS included outcomes related to mortality, organ failure, complications, interventions/management, and social factors. CONCLUSION: Through an iterative consensus process, content experts agreed on a COS for the management of ANP. This will help shape future research to generate data suitable for pooling and other statistical analyses that may guide clinical practice. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level V.
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Consenso , Técnica Delphi , Pancreatite Necrosante Aguda , Pancreatite Necrosante Aguda/cirurgia , Pancreatite Necrosante Aguda/mortalidade , Humanos , Avaliação de Resultados em Cuidados de SaúdeRESUMO
INTRODUCTION: Chronic pancreatitis (CP) is a progressive fibroinflammatory disorder lacking therapies and biomarkers. Neutrophil gelatinase-associated lipocalin (NGAL) is a proinflammatory cytokine elevated during inflammation that binds fatty acids (FAs) such as linoleic acid. We hypothesized that systemic NGAL could serve as a biomarker for CP and, with FAs, provide insights into inflammatory and metabolic alterations. METHODS: NGAL was measured by immunoassay, and FA composition was measured by gas chromatography in plasma (n = 171) from a multicenter study, including controls (n = 50), acute and recurrent acute pancreatitis (AP/RAP) (n = 71), and CP (n = 50). Peripheral blood mononuclear cells (PBMCs) from controls (n = 16), AP/RAP (n = 17), and CP (n = 15) were measured by cytometry by time-of-flight. RESULTS: Plasma NGAL was elevated in subjects with CP compared with controls (area under the curve [AUC] = 0.777) or AP/RAP (AUC = 0.754) in univariate and multivariate analyses with sex, age, body mass index, and smoking (control AUC = 0.874; AP/RAP AUC = 0.819). NGAL was elevated in CP and diabetes compared with CP without diabetes ( P < 0.001). NGAL + PBMC populations distinguished CP from controls (AUC = 0.950) or AP/RAP (AUC = 0.941). Linoleic acid was lower, whereas dihomo-γ-linolenic and adrenic acids were elevated in CP ( P < 0.05). Linoleic acid was elevated in CP with diabetes compared with CP subjects without diabetes ( P = 0.0471). DISCUSSION: Elevated plasma NGAL and differences in NGAL + PBMCs indicate an immune response shift that may serve as biomarkers of CP. The potential interaction of FAs and NGAL levels provide insights into the metabolic pathophysiology and improve diagnostic classification of CP.
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Biomarcadores , Lipocalina-2 , Pancreatite Crônica , Humanos , Masculino , Feminino , Lipocalina-2/sangue , Pancreatite Crônica/sangue , Pancreatite Crônica/diagnóstico , Pessoa de Meia-Idade , Biomarcadores/sangue , Adulto , Estudos Transversais , Leucócitos Mononucleares/metabolismo , Idoso , Ácidos Graxos/sangue , Ácidos Graxos/metabolismo , Ácido Linoleico/sangue , Estudos de Casos e ControlesRESUMO
Importance: Intraductal papillary mucinous neoplasms (IPMNs) are pancreatic cysts that can give rise to pancreatic cancer (PC). Limited population data exist on their prevalence, natural history, or risk of malignant transformation (IPMN-PC). Objective: To fill knowledge gaps in epidemiology of IPMNs and associated PC risk by estimating population prevalence of IPMNs, associated PC risk, and proportion of IPMN-PC. Design, Setting, and Participants: : This retrospective cohort study was conducted in Olmsted County, Minnesota. Using the Rochester Epidemiology Project (REP), patients aged 50 years and older with abdominal computed tomography (CT) scans between 2000 and 2015 were randomly selected (CT cohort). All patients from the REP with PC between 2000 and 2019 were also selected (PC cohort). Data were analyzed from November 2021 through August 2023. Main outcomes and Measures: CIs for PC incidence estimates were calculated using exact methods with the Poisson distribution. Cox models were used to estimate age, sex, and stage-adjusted hazard ratios for time-to-event end points. Results: The CT cohort included 2114 patients (1140 females [53.9%]; mean [SD] age, 68.6 [12.1] years). IPMNs were identified in 231 patients (10.9%; 95% CI, 9.7%-12.3%), most of which were branch duct (210 branch-duct [90.9%], 16 main-duct [6.9%], and 5 mixed [2.2%] IPMNs). There were 5 Fukuoka high-risk (F-HR) IPMNs (2.2%), 39 worrisome (F-W) IPMNs (16.9%), and 187 negative (F-N) IPMNs (81.0%). After a median (IQR) follow-up of 12.0 (8.1-15.3) years, 4 patients developed PC (2 patients in F-HR and 2 patients in F-N groups). The PC incidence rate per 100 person years for F-HR IPMNs was 34.06 incidents (95% CI, 4.12-123.02 incidents) and not significantly different for patients with F-N IPMNs compared with patients without IPMNs (0.16 patients; 95% CI, 0.02-0.57 patients vs 0.11 patients; 95% CI, 0.06-0.17 patients; P = .62). The PC cohort included 320 patients (155 females [48.4%]; mean [SD] age, 72.0 [12.3] years), and 9.8% (95% CI, 7.0%-13.7%) had IPMN-PC. Compared with 284 patients with non-IPMN PC, 31 patients with IPMN-PC were older (mean [SD] age, 76.9 [9.2] vs 71.3 [12.5] years; P = .02) and more likely to undergo surgical resection (14 patients [45.2%] vs 60 patients [21.1%]; P = .003) and more-frequently had nonmetastatic PC at diagnosis (20 patients [64.5%] vs 130 patients [46.8%]; P = .047). Patients with IPMN-PC had better survival (adjusted hazard ratio, 0.62; 95% CI, 0.40-0.94; P = .03) than patients with non-IPMN PC. Conclusions and Relevance: In this study, CTs identified IPMNs in approximately 10% of patients aged 50 years or older. PC risk in patients with F-N IPMNs was low and not different compared with patients without IPMNs; approximately 10% of patients with PC had IPMN-PC, and they had better survival compared with patients with non-IPMN PC.
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Neoplasias Císticas, Mucinosas e Serosas , Neoplasias Intraductais Pancreáticas , Neoplasias Pancreáticas , Feminino , Humanos , Pessoa de Meia-Idade , Idoso , Neoplasias Intraductais Pancreáticas/diagnóstico por imagem , Neoplasias Intraductais Pancreáticas/epidemiologia , Neoplasias Intraductais Pancreáticas/patologia , Estudos Retrospectivos , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/patologia , Neoplasias PancreáticasRESUMO
PURPOSE OF REVIEW: The purpose of the review is to critically evaluate the evidence from the literature to establish the current perspective on fluid resuscitation (FR) in acute pancreatitis (AP). We will review the rationale, type of fluid, rate of administration, total volume, duration, monitoring, ideal outcomes to be studied in clinical trials and recommendations for future studies. RECENT FINDINGS: FR remains the key component of supportive therapy in AP. The paradigm has shifted from administration of aggressive fluid resuscitation towards more moderate FR strategies. Lactated Ringer's remains the preferred fluid for resuscitation. There remain critical gaps in knowledge regarding the end point(s) to indicate adequate resuscitation, and accurate assessments of fluid sequestration and intravascular volume deficit in AP. SUMMARY: There is insufficient evidence to state that goal-directed therapy, using any of the parameters to guide fluid administration, reduces the risk of persistent organ failure, infected pancreatic necrosis, or mortality in AP, as well as the most appropriate method for the same.
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Pancreatite Necrosante Aguda , Humanos , Doença Aguda , Pancreatite Necrosante Aguda/terapia , Lactato de Ringer , Hidratação/métodosRESUMO
Pancreatic fungal infection (PFI) in patients with necrotizing pancreatitis can lead to significant morbidity and mortality. The incidence of PFI has increased during the past decade. Our study aimed to provide contemporary observations on the clinical characteristics and outcomes of PFI in comparison to pancreatic bacterial infection and necrotizing pancreatitis without infection. We conducted a retrospective study of patients with necrotizing pancreatitis (acute necrotic collection or walled-off necrosis), who underwent pancreatic intervention (necrosectomy and/or drainage) and had tissue/fluid culture between 2005 and 2021. We excluded patients with pancreatic procedures prior to hospitalization. Multivariable logistic and Cox regression models were fitted for in-hospital and 1-year survival outcomes. A total of 225 patients with necrotizing pancreatitis were included. Pancreatic fluid and/or tissue was obtained from endoscopic necrosectomy and/or drainage (76.0%), CT-guided percutaneous aspiration (20.9%), or surgical necrosectomy (3.1%). Nearly half of the patients had PFI with or without concomitant bacterial infection (48.0%), while the remaining patients had either bacterial infection alone (31.1%) or no infection (20.9%). In multivariable analysis to assess the risk of PFI or bacterial infection alone, only previous pancreatitis was associated with an increased odds of PFI vs. no infection (OR 4.07, 95% CI 1.13-14.69, p = .032). Multivariable regression analyses revealed no significant differences in in-hospital outcomes or one-year survival between the 3 groups. Pancreatic fungal infection occurred in nearly half of necrotizing pancreatitis. Contrary to many of the previous reports, there was no significant difference in important clinical outcomes between the PFI group and each of the other two groups.
We examined 225 patients with necrotizing pancreatitis who had tissue/fluid culture available and found that nearly half of the patients had pancreatic fungal infection. Interestingly, there was no difference in clinical outcomes between the fungal infection group and non-fungal infection groups.
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Infecções Bacterianas , Micoses , Pancreatite Necrosante Aguda , Animais , Estudos Retrospectivos , Pancreatite Necrosante Aguda/complicações , Pancreatite Necrosante Aguda/cirurgia , Pancreatite Necrosante Aguda/microbiologia , Pancreatite Necrosante Aguda/veterinária , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/veterinária , Micoses/complicações , Micoses/veterinária , Resultado do TratamentoRESUMO
PURPOSE: To determine the diagnostic performance of parenchymal MRI features differentiating CP from controls. METHODS: This prospective study performed abdominal MRI scans at seven institutions, using 1.5 T Siemens and GE scanners, in 50 control and 51 definite CP participants, from February 2019 to May 2021. MRI parameters included the T1-weighted signal intensity ratio of the pancreas (T1 score), arterial-to-venous enhancement ratio (AVR) during venous and delayed phases, pancreas volume, and diameter. We evaluated the diagnostic performance of these parameters individually and two semi-quantitative MRI scores derived using logistic regression: SQ-MRI Model A (T1 score, AVR venous, and tail diameter) and Model B (T1 score, AVR venous, and volume). RESULTS: When compared to controls, CP participants showed a significantly lower mean T1 score (1.11 vs. 1.29), AVR venous (0.86 vs. 1.45), AVR delayed (1.07 vs. 1.57), volume (54.97 vs. 80.00 ml), and diameter of the head (2.05 vs. 2.39 cm), body (2.25 vs. 2.58 cm), and tail (1.98 vs. 2.51 cm) (p < 0.05 for all). AUCs for these individual MR parameters ranged from 0.66 to 0.79, while AUCs for the SQ-MRI scores were 0.82 and 0.81 for Model A (T1 score, AVR venous, and tail diameter) and Model B (T1 score, AVR venous, and volume), respectively. After propensity-matching adjustments for covariates, AUCs for Models A and B of the SQ-MRI scores increased to 0.92 and 0.93, respectively. CONCLUSION: Semi-quantitative parameters of the pancreatic parenchyma, including T1 score, enhancement ratio, pancreas volume, diameter and multi-parametric models combining these parameters are helpful in diagnosis of CP. Longitudinal analyses including more extensive population are warranted to develop new diagnostic criteria for CP.
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Pâncreas , Pancreatite Crônica , Humanos , Estudos Prospectivos , Imageamento por Ressonância Magnética/métodosRESUMO
Debilitating abdominal pain is a common symptom affecting most patients with chronic pancreatitis (CP). There are multiple underlying mechanisms that contribute to CP-related pain, which makes successful treatment difficult. The identification of biomarkers for subtypes of pain could provide viable targets for nonopioid interventions and the development of mechanistic approaches to pain management in CP. Nineteen inflammation- and nociception-associated proteins were measured in serum collected from 358 subjects with definite CP enrolled in PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies, a prospective observational study of pancreatitis in US adult subjects. First, serum levels of putative biomarkers were compared between CP subjects with and without pain. Only platelet-derived growth factor B (PDGF-B) stood out, with levels significantly higher in the CP pain group as compared to subjects with no pain. Subjects with pain were then stratified into 4 pain subtypes (Neuropathic, Nociceptive, Mixed, and Unclassified). A comparison of putative biomarker concentration among 5 groups (no pain and 4 pain subtypes) identified unique proteins that were correlated with pain subtypes. Serum transforming growth factor beta 1 (TGFß1) level was significantly higher in the Nociceptive pain group compared to the No pain group, suggesting that TGFß1 may be a biomarker for nociceptive pain. The Neuropathic pain only group was too small to detect statistical differences. However, glycoprotein 130 (GP130), a coreceptor for interleukin 6, was significantly higher in the Mixed pain group compared to the groups lacking a neuropathic pain component. These data suggest that GP130 may be a biomarker for neuropathic pain in CP. PERSPECTIVE: Serum TGFß1 and GP130 may be biomarkers for nociceptive and neuropathic CP pain, respectively. Preclinical data suggest inhibiting TGFß1 or GP130 reduces CP pain in rodent models, indicating that additional translational and clinical studies may be warranted to develop a precision medicine approach to the management of pain in CP.
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Dor Crônica , Neuralgia , Dor Nociceptiva , Pancreatite Crônica , Adulto , Humanos , Biomarcadores , Receptor gp130 de Citocina , Neuralgia/diagnóstico , Neuralgia/etiologia , Neuralgia/tratamento farmacológico , Nociceptividade , Pancreatite Crônica/complicações , Pancreatite Crônica/diagnósticoRESUMO
BACKGROUND AND AIMS: Patients with infected or symptomatic walled-off necrosis (WON) have high morbidity and health care utilization. Despite the recent adoption of nonsurgical treatment approaches, WON management remains nonalgorithmic. We investigated the impact of a protocolized early necrosectomy approach compared with a nonprotocolized, clinician-driven approach on important clinical outcomes. METHODS: Records were reviewed for consecutive patients with WON who underwent a protocolized endoscopic drainage with a lumen-apposing metal stent (cases), and for patients with WON treated with a lumen-apposing metal stent at the same tertiary referral center who were not managed according to the protocol (control subjects). The protocol required repeat cross-sectional imaging within 14 days after lumen-apposing metal stent placement, with regularly scheduled endoscopic necrosectomy if WON diameter reduction was <50%. Control patients were treated according to their clinician's preference without an a priori strategy. Inverse probability of treatment weighting-adjusted analysis was used to evaluate the influence of being in the protocolized group on time to resolution. RESULTS: A total of 24 cases and 47 control subjects were included. There were no significant differences in baseline characteristics. Although numbers of endoscopies and necrosectomies were similar, cases had lower adverse event rates, shorter intensive care unit stay, and required nutritional support for fewer days. On matched multivariate Cox regression, cases had earlier WON resolution (hazard ratio, 5.73; 95% confidence interval, 2.62-12.5). This was confirmed in the inverse probability of treatment weighting-adjusted analysis (hazard ratio, 3.4; 95% confidence interval, 1.92-6.01). CONCLUSIONS: A protocolized strategy resulted in faster WON resolution compared with a discretionary approach without the need for additional therapeutic interventions, and with a better safety profile and decreased health care utilization.
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Pancreatite Necrosante Aguda , Stents , Humanos , Estudos Retrospectivos , Stents/efeitos adversos , Endoscopia/métodos , Drenagem/métodos , Necrose/etiologia , Pancreatite Necrosante Aguda/cirurgia , Resultado do Tratamento , EndossonografiaRESUMO
BACKGROUND & AIMS: Pancreatitis is a disease continuum, starting with acute pancreatitis (AP) and progressing in some cases to recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP). Currently, there are no approved therapies or early diagnostic or prognostic biomarkers for pancreatitis. The current study examined whether patient serum immune profiling could identify noninvasive biomarkers and provide mechanistic insight into the disease continuum of pancreatitis. METHODS: Using Olink immunoassay, we assessed the protein levels of 92 immune markers in serum samples from participants enrolled in the Prospective Evaluation of Chronic Pancreatitis for Epidemiologic and Translational Studies (PROCEED) study of the Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC) consortium. Samples (N = 231) were obtained from individuals without pancreatic disease (n = 56) and from those with chronic abdominal pain (CAP) (n = 24), AP (n = 38), RAP (n = 56), and CP (n = 57). RESULTS: A total of 33 immune markers differentiated the combined pancreatitis groups from controls. Immune markers related to interleukin (IL) 17 signaling distinguished CP from AP and RAP. Similarly, the serum level of IL17A and C-C motif chemokine ligand 20 differentiated CP from CAP, suggesting the involvement of T helper 17 cells in CP pathogenesis. The receiver operator characteristic curve with 2 immune markers (IL17A and sulfotransferase 1A1) could differentiate CP from CAP (optimistic area under the curve = 0.78). The macrophage classical activation pathway elevated along the continuum of pancreatitis, suggesting an accumulation of proinflammatory signals over disease progression. Several immune markers were associated with smoking, alcohol, and diabetes status. CONCLUSIONS: Immune profiling of serum samples from a large pancreatitis cohort led to identifying distinct immune markers that could serve as potential biomarkers to differentiate the varying pancreatitis disease states. In addition, the finding of IL17 signaling in CP could provide insight into the immune mechanisms underlying disease progression.
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Diabetes Mellitus , Pancreatite Crônica , Humanos , Doença Aguda , Pancreatite Crônica/diagnóstico , Pancreatite Crônica/epidemiologia , Progressão da Doença , Dor Abdominal , BiomarcadoresAssuntos
Cisto Pancreático , Neoplasias Pancreáticas , Humanos , Estudos Prospectivos , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Cisto Pancreático/diagnóstico por imagem , Cisto Pancreático/genética , Sequenciamento de Nucleotídeos em Larga Escala , Biomarcadores Tumorais/genéticaRESUMO
OBJECTIVE: Diabetes that arises from chronic pancreatitis (CP) is associated with increased morbidity and mortality. Methods to predict which patients with CP are at greatest risk for diabetes are urgently needed. We aimed to examine independent risk factors for diabetes in a large cohort of patients with CP. RESEARCH DESIGN AND METHODS: This cross-sectional study comprised 645 individuals with CP enrolled in the PROCEED study, of whom 276 had diabetes. We conducted univariable and multivariable regression analyses of potential risk factors for diabetes. Model performance was assessed by area under the receiver operating characteristic curve (AUROC) analysis, and accuracy was evaluated by cross validation. Exploratory analyses were stratified according to the timing of development of diabetes relative to the diagnosis of pancreatitis. RESULTS: Independent correlates of diabetes in CP included risk factors for type 2 diabetes (older age, overweight/obese status, male sex, non-White race, tobacco use) as well as pancreatic disease-related factors (history of acute pancreatitis complications, nonalcoholic etiology of CP, exocrine pancreatic dysfunction, pancreatic calcification, pancreatic atrophy) (AUROC 0.745). Type 2 diabetes risk factors were predominant for diabetes occurring before pancreatitis, and pancreatic disease-related factors were predominant for diabetes occurring after pancreatitis. CONCLUSIONS: Multiple factors are associated with diabetes in CP, including canonical risk factors for type 2 diabetes and features associated with pancreatitis severity. This study lays the groundwork for the future development of models integrating clinical and nonclinical data to identify patients with CP at risk for diabetes and identifies modifiable risk factors (obesity, smoking) on which to focus for diabetes prevention.
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Diabetes Mellitus Tipo 2 , Pancreatite Crônica , Humanos , Masculino , Diabetes Mellitus Tipo 2/complicações , Doença Aguda , Estudos Transversais , Modelos Estatísticos , Prognóstico , Pancreatite Crônica/complicações , Fatores de Risco , Obesidade/complicaçõesRESUMO
BACKGROUND/OBJECTIVES: Current treatments for chronic pancreatitis focus on symptom management and therapeutics targeting disease reversal are lacking. Given the role of the cyclooxygenase-2 (COX-2) enzyme in producing prostaglandin E2 (PGE2), a key component in the inflammatory pathway of chronic pancreatitis, this study evaluates the physiologic effect of oral indomethacin, a COX-2 inhibitor, on PGE2 levels in pancreatic fluid. METHODS: This pilot two-center randomized controlled trial seeks to examine 32 subjects with chronic pancreatitis who have no contraindications to indomethacin. Subjects will be randomized to either oral indomethacin 50 mg twice a day or placebo twice a day for a total of 28 days. Baseline (pre-treatment) assessment of pain and quality of life will be performed using the Brief Pain Inventory and the PROMIS-10 questionnaires, respectively. Biological specimens including blood, urine, and saliva will be collected at pre-treatment and post-treatment(day 28). Endoscopic pancreatic function testing with concomitant pancreatic fluid collection will also be performed pre- and post-treatment to assess the change in pancreatic fluid PGE2 levels. The relationship between pancreatic fluid PGE2 levels with blood and saliva PGE2 levels will be examined. CONCLUSIONS: This study will elucidate the effect of oral indomethacin on PGE2 levels in the pancreas to assess its role in the inflammatory pathway of chronic pancreatitis. Should indomethacin significantly reduce PGE2 levels, this may represent a potential disease-altering treatment for chronic pancreatitis.
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Indometacina , Pancreatite Crônica , Humanos , Indometacina/uso terapêutico , Qualidade de Vida , Pancreatite Crônica/diagnóstico , Anti-Inflamatórios não Esteroides/uso terapêutico , Pâncreas/metabolismo , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto , Ensaios Clínicos Fase I como Assunto , Ensaios Clínicos Fase II como AssuntoRESUMO
ABSTRACT: Pain is common in chronic pancreatitis (CP) and profoundly reduces quality of life (QoL). Multiple underlying mechanisms contribute to a heterogenous pain experience and reduce efficacy of pain management. This study was designed to characterize the distribution of mechanism-based pain phenotypes in painful CP. The data analyzed were collected as part of the PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies, an NCI/NIDDK-funded longitudinal study of the natural history of CP. The PROspective Evaluation of Chronic pancreatitis for EpidEmiologic and translational stuDies includes patient-reported outcome (PRO) measures of pain, medication use, global health, and QoL. Of subjects (N = 681) with CP, 80% experienced abdominal pain within the year before enrollment. Subjects who experienced pain in the week before enrollment (N = 391) completed PROMIS Neuropathic and Nociceptive Pain Quality instruments which were then used to classify them by pain type: 40% had nociceptive, 5% had neuropathic-like, and 32% had both types of pain. The prevalence of having both types of pain was higher among women and subjects with diabetes mellitus, whereas nociceptive-only pain was more prevalent among men and those with pancreatic duct stricture. Other factors, including pain medication use and healthcare utilization, did not differ between groups based on pain type. Subjects in the Both group had significantly worse health and QoL scores relative to those with nociceptive-only pain, suggesting that using psychosocial pain surveys may be useful for understanding pain subtypes in patients with CP. Additional research is needed to identify biochemical and biophysical signatures that may associate with and predict responses to mechanism-specific interventions.