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A 73-year-old male patient was referred to us with a long Barrett's esophagus (BE). He had a history of pulmonary embolism under anticoagulant therapy. Esophagogastroduodenoscopy showed a C8M9 BE with no macroscopic lesions. Random biopsies from the BE revealed multifocal high-grade dysplasia. The case was discussed in a multidisciplinary team conference and the decision for full resection of BE with endoscopic submucosal dissection (ESD) was made. Considering the large ESD resection and the high risk of stricture, we developed a novel preventive technique: the "steroid lifting method" for submucosal injection during ESD. Complete circumferential ESD with en bloc resection was performed using the "steroid lifting method", without adverse events. Oral liquids were initiated on day 1 and the patient was discharged on day 4. Oral prednisolone (30 mg per day) was started and tapered for a total of 6 weeks. The pathological examination confirmed multifocal high-grade dysplasia, with radical and curative resection. The patient had neither stricture, dysphagia nor recurrence of Barrett's mucosa at the 2, 6, 12, and 24-month follow-up. International guidelines recommend oral prednisolone and triamcinolone injection to prevent stricture formation in large ESD of esophageal squamous cell carcinoma. However, there is no solid data on BE ESD. The risk factors for stricture formation and the optimal preventive management after large BE ESD is not known. The "steroid lifting method" might be an option in this context. Large prospective studies addressing stricture formation and preventive measures on BE ESD are necessary.
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BACKGROUND: The duration of an endoscopic retrograde cholangiopancreatography (ERCP) is influenced by a multitude of factors. The aim of this study was to describe the factors influencing ERCP time and to create a tool for preintervention estimation of ERCP time. METHODS: Data from 74 248 ERCPs performed from 2010 to 2019 were extracted from the Swedish National Quality Registry (GallRiks) to identify variables predictive for ERCP time using linear regression analyses and root mean squared error (RMSE) as a loss function. Ten variables were combined to create an estimation tool for ERCP duration. The tool was externally validated using 9472 ERCPs from 2020 to 2021. RESULTS: Mean (SD) ERCP time was 36.8 (25.3) minutes. Indications with the strongest influence on ERCP time were primary sclerosing cholangitis and chronic pancreatitis. Hilar and intrahepatic biliary strictures and interventions on the pancreatic duct were the anatomic features that most strongly affected ERCP time. The procedure steps with most influence were intraductal endoscopy, lithotripsy, dilation, and papillectomy. Based on these results, we built and validated the SW: edish E: stimation of E: RCP T: ime (SWEET) tool, which is based on a 10-factor scoring system (e.g. 5 minutes for bile duct cannulation and 15 minutes for pancreatic duct cannulation) and predicted ERCP time with an average difference between actual and predicted duration of 17.5 minutes during external validation. CONCLUSIONS: Based on new insights into the factors affecting ERCP time, we created the SWEET tool, the first specific tool for preintervention estimation of ERCP time, which is easy-to-apply in everyday clinical practice, to guide efficient ERCP scheduling.
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Screening of the general population for cancer is a matter of primary prevention reducing the burden of disease. Whilst this is successful for several cancers including breast, colon and prostate, the situation to screen and hence prevent pancreatic cancer is different. The organ is not as accessible to simple physical exam or biological samples (fecal or blood test). Neither exists a blood test such as PSA that is cost-effective. Reviewing the evidence from screening risk groups for pancreatic cancer, one must conclude that there is no rational at present to screen the general population, for a lack of appropriate tests.
Subject(s)
Early Detection of Cancer , Pancreatic Neoplasms , Humans , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/prevention & control , Early Detection of Cancer/methods , Genetic Predisposition to Disease , Population Surveillance/methods , Mass Screening/methods , Male , FemaleABSTRACT
BACKGROUND AND AIMS: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a precursor of pancreatic cancer. While earlier research has shown a high prevalence of synchronous/metachronous extrapancreatic tumors in IPMN patients, these studies have often been small with retrospective data collection. The aim of the study was to examine absolute and relative risks of non-pancreatic gastrointestinal (GI) cancer precursors and mortality in histologically confirmed IPMN. METHODS: Through the nationwide ESPRESSO histopathology cohort, we retrieved data on IPMN between 1965 and 2016. Each index case was matched to ≤5 general population controls. Through Cox regression, we estimated hazard ratios (HRs) for future GI cancer precursors and death. RESULTS: A total of 117 patients with IPMN and 539 age- and sex-matched controls were included. Over a median of 2.1 years of follow up, we confirmed two (1.7%) incident GI cancer precursors in IPMN vs. four (0.7%) in controls, corresponding to an HR of 1.89 (95%CI = 0.34-10.55). By contrast, IPMN patients were at increased risk of death (HR 3.61 (95%CI = 1.79-7.27)). The most common cause of death in IPMN was pancreatic cancer (n = 14; 45.2% of all deaths). CONCLUSIONS: We found no association between IPMN and other GI cancer precursors. This argues against comprehensive routine surveillance for other GI cancer precursors in IPMN patients. Mortality was increased in IPMN with pancreatic cancer being the most common cause of death, indicating the need for lifelong follow up in all resected and non-resected patients with IPMN. However, results should be confirmed in larger cohorts.
Subject(s)
Gastrointestinal Neoplasms , Pancreatic Intraductal Neoplasms , Pancreatic Neoplasms , Humans , Female , Male , Aged , Middle Aged , Gastrointestinal Neoplasms/mortality , Gastrointestinal Neoplasms/pathology , Pancreatic Neoplasms/mortality , Pancreatic Neoplasms/pathology , Pancreatic Intraductal Neoplasms/mortality , Pancreatic Intraductal Neoplasms/pathology , Retrospective Studies , Case-Control Studies , Proportional Hazards Models , Aged, 80 and over , Adult , Adenocarcinoma, Mucinous/mortality , Adenocarcinoma, Mucinous/pathology , Risk Factors , Carcinoma, Pancreatic Ductal/mortality , Carcinoma, Pancreatic Ductal/pathologyABSTRACT
BACKGROUND & AIMS: Autoimmune pancreatitis (AIP) is an immune-mediated disease of the pancreas with distinct pathophysiology and manifestations. Our aims were to characterize type 1 AIP in a large pan-European cohort and study the effectiveness of current treatment regimens. METHODS: We retrospectively analyzed adults diagnosed since 2005 with type 1 or not-otherwise-specified AIP in 42 European university hospitals. Type 1 AIP was uniformly diagnosed using specific diagnostic criteria. Patients with type 2 AIP and those who had undergone pancreatic surgery were excluded. The primary end point was complete remission, defined as the absence of clinical symptoms and resolution of the index radiologic pancreatic abnormalities attributed to AIP. RESULTS: We included 735 individuals with AIP (69% male; median age, 57 years; 85% White). Steroid treatment was started in 634 patients, of whom 9 (1%) were lost to follow-up. The remaining 625 had a 79% (496/625) complete, 18% (111/625) partial, and 97% (607/625) cumulative remission rate, whereas 3% (18/625) did not achieve remission. No treatment was given in 95 patients, who had a 61% complete (58/95), 19% partial (18/95), and 80% cumulative (76/95) spontaneous remission rate. Higher (≥0.4 mg/kg/day) corticosteroid doses were no more effective than lower (<0.4 mg/kg/day) doses (odds ratio, 0.428; 95% confidence interval, 0.054-3.387) and neither was a starting dose duration >2 weeks (odds ratio, 0.908; 95% confidence interval, 0.818-1.009). Elevated IgG4 levels were independently associated with a decreased chance of complete remission (odds ratio, 0.639; 95% confidence interval, 0.427-0.955). Relapse occurred in 30% of patients. Relapses within 6 months of remission induction were independent of the steroid-tapering duration, induction treatment duration, and total cumulative dose. CONCLUSIONS: Patients with type 1 AIP and elevated IgG4 level may need closer monitoring. For remission induction, a starting dose of 0.4 mg/kg/day for 2 weeks followed by a short taper period seems effective. This study provides no evidence to support more aggressive regimens.
Subject(s)
Autoimmune Pancreatitis , Humans , Male , Middle Aged , Female , Retrospective Studies , Autoimmune Pancreatitis/drug therapy , Autoimmune Pancreatitis/diagnosis , Europe , Aged , Treatment Outcome , Adult , Steroids/therapeutic use , Steroids/administration & dosage , Aged, 80 and overABSTRACT
BACKGROUND AND AIMS: Chronic pancreatitis may cause intractable abdominal pain, with total pancreatectomy sometimes being the last resort. To mitigate the subsequent diabetes, total pancreatectomy can be followed by islet autotransplantation (TP-IAT). The primary aim of this study was to assess the outcomes in patients undergoing TP-IAT at Karolinska University Hospital with respect to safety, postoperative complications, and islet graft function. A secondary aim was to compare liver to skeletal muscle as autotransplantation sites. METHODS: Single-center observational cohort study on patients undergoing TP-IAT. Islets were transplanted either into the liver or skeletal muscle. Data on baseline characteristics and pretransplantory conditions were collected. Outcome measures included mortality and major postoperative complications as well as the glycemic measures: insulin use, fasting C-peptide, and HbA1c. RESULTS: Between 2004 and 2020, 24 patients underwent TP-IAT. Islets were transplanted into the liver in 9 patients and into skeletal muscle in 15 patients. There was no 90-day mortality, and major complications (Clavien-Dindo ⩾IIIa) occurred in 26.7%, all related to the procedure of total pancreatectomy. Fasting C-peptide could be detected postoperatively, with higher levels in patients receiving islet autotransplantation into the liver (p = 0.006). Insulin independence was not achieved, although insulin doses at last follow-up were significantly lower in patients receiving islet autotransplantation into the liver compared to skeletal muscle (p = 0.036). CONCLUSION: TP-IAT is safe and associated with tolerable risk, the component of islet autotransplantation being seemingly harmless. Although islet grafts maintain some endocrine function, insulin independence should not be expected. Regarding islet autotransplantation sites, the liver seems superior to skeletal muscle. CLINICAL TRIAL REGISTRATION: Not applicable.
Subject(s)
Islets of Langerhans Transplantation , Pancreatectomy , Pancreatitis, Chronic , Transplantation, Autologous , Humans , Pancreatectomy/methods , Islets of Langerhans Transplantation/methods , Male , Female , Middle Aged , Pancreatitis, Chronic/surgery , Adult , Postoperative Complications/epidemiology , Treatment Outcome , Muscle, Skeletal/transplantation , LiverABSTRACT
Video 1Resection of a gastric lesion using Topflight ESD.
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INTRODUCTION: Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated condition associated with fibroinflammatory lesions that can occur at almost any anatomical site. It often presents as a multiorgan disease that may mimic malignancy, infection, or other immune-mediated conditions. Autoimmune pancreatitis (AIP) type 1 is the most prominent manifestation of IgG4-RD in the digestive tract, with common extra-pancreatic inflammation. We present the first patient with AIP and involvement of the testicles and nasal cavity. PATIENT AND METHODS: A case of a patient with AIP type 1 and other organ involvement (bile ducts, testicles, nasal polyps, and lungs) is described. Additionally, a systematic review of AIP type 1 with testicular and nasal involvement was conducted. RESULTS: The systematic review found two cases of AIP type 1 with testicular involvement and 143 cases with AIP type 1 with nasal cavity involvement. None of them had both testicular and nasal involvement. CONCLUSIONS: This is the first case of AIP type 1 with other organ involvement, including testicular and nasal involvement, to be described. The number of patients with nasal and testicular involvement described in the literature is low. Creating awareness of this rare clinical condition is necessary, especially due to the very effective available treatment with corticosteroids and rituximab.
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OBJECTIVES: Intraoperative pancreatoscopy is a promising procedure that might guide surgical resection for suspected main duct (MD) and mixed type (MT) intraductal papillary mucinous neoplasms (IPMNs). The aim of the present study was to assess the diagnostic yield and clinical impact of intraoperative pancreatoscopy in patients operated on for MD and MT-IPMNs. METHODS: This is a retrospective cohort study. Patients undergoing surgery for suspected MD or MT-IPMN underwent intraoperative pancreatoscopy and frozen section analysis. In all patients who required extended resection due to pancreatoscopic findings, we compared the final histology with the results of the intraoperative frozen section analysis. RESULTS: In total, 46 patients, 48% females, mean age (range) 67 years (45-82 years) underwent intraoperative pancreatoscopy. No mortality or procedure related complications were observed. Pancreatoscopy changed the operative course in 30 patients (65%), leading to extended resections in 20 patients (43%) and to parenchyma sparing procedures in 10 patients (22%). Analyzing the group of patients who underwent extended resections, 7 (35%) displayed lesions that needed further surgical treatment (six high grade dysplasia and one with G1 pancreatic neuroendocrine tumor) and among those 7, just 1 (14%) would have been detected exclusively with histological frozen section analysis of the transection margin. The combination of both pancreatoscopy and frozen section analysis lead to 86% sensitivity and 92% specificity for the detection of pathological tissue in the remnant pancreas. CONCLUSION: Intraoperative pancreatoscopy is a safe and feasible procedure and might allow the detection of skip lesions during surgery for suspect MD-involving IPMNs.
Subject(s)
Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Female , Humans , Aged , Male , Pilot Projects , Retrospective Studies , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/surgery , Pancreatic Neoplasms/pathology , Pancreas/diagnostic imaging , Pancreas/surgery , Pancreas/pathology , Pancreatectomy/methods , Carcinoma, Pancreatic Ductal/pathologyABSTRACT
Sulfur is an essential element of life. Thiol-containing metabolites in all organisms are involved in the regulation of diverse biological processes. Especially, the microbiome produces bioactive metabolites or biological intermediates of this compound class. The analysis of thiol-containing metabolites is challenging due to the lack of specific tools, making these compounds difficult to investigate selectively. We have now developed a new methodology comprising bicyclobutane for chemoselective and irreversible capturing of this metabolite class. We utilized this new chemical biology tool immobilized onto magnetic beads for the investigation of human plasma, fecal samples, and bacterial cultures. Our mass spectrometric investigation detected a broad range of human, dietary and bacterial thiol-containing metabolites and we even captured the reactive sulfur species cysteine persulfide in both fecal and bacterial samples. The described comprehensive methodology represents a new mass spectrometric strategy for the discovery of bioactive thiol-containing metabolites in humans and the microbiome.
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BACKGROUND: Acute and chronic pancreatitis constitute a continuum of inflammatory disease of the pancreas with an increasing incidence in most high-income countries. A subset of patients with a history of pancreatitis suffer from recurrence of acute pancreatitis attacks, which accelerate disease progression towards end-stage chronic pancreatitis with loss of exocrine and endocrine function. There is currently no available prophylactic treatment for recurrent acute pancreatitis apart from removing risk factors, which is not always possible. Pain is the primary symptom of acute pancreatitis, which induces the endogenous release of opioids. This may further be potentiated by opioid administration for pain management. Increased exposure to opioids leads to potentially harmful effects on the gastrointestinal tract, including, e.g. increased sphincter tones and decreased fluid secretion, which may impair pancreatic ductal clearance and elevate the risk for new pancreatitis attacks and accelerate disease progression. Peripherally acting µ-opioid receptor antagonists (PAMORAs) have been developed to counteract the adverse effects of opioids on the gastrointestinal tract. We hypothesize that the PAMORA naldemedine will reduce the risk of new pancreatitis attacks in patients with recurrent acute pancreatitis and hence decelerate disease progression. METHODS: The study is a double-blind, randomized controlled trial with allocation of patients to either 0.2 mg naldemedine daily or matching placebo for 12 months. A total of 120 outpatients will be enrolled from five specialist centres in Denmark and Sweden. The main inclusion criteria is a history of recurrent acute pancreatitis (minimum of two confirmed pancreatitis attacks). The primary endpoint is time to acute pancreatitis recurrence after randomization. Secondary outcomes include changes in quality of life, gastrointestinal symptom scores, new-onset diabetes, exocrine pancreatic insufficiency, disease severity, health care utilization, adherence to treatment, and frequency of adverse events. Exploratory outcomes are included for mechanistic linkage and include the progression of chronic pancreatitis-related findings on magnetic resonance imaging (MRI) and changes in circulating blood markers of inflammation and fibrosis. DISCUSSION: This study investigates if naldemedine can change the natural course of pancreatitis in patients with recurrent acute pancreatitis and improve patient outcomes. TRIAL REGISTRATION: EudraCT no. 2021-000069-34. CLINICALTRIALS: gov NCT04966559. Registered on July 8, 2021.
Subject(s)
Narcotic Antagonists , Pancreatitis, Chronic , Humans , Narcotic Antagonists/adverse effects , Quality of Life , Acute Disease , Analgesics, Opioid/adverse effects , Pancreatitis, Chronic/drug therapy , Disease Progression , Treatment Outcome , Double-Blind Method , Randomized Controlled Trials as TopicABSTRACT
INTRODUCTION: The prevalence of non-alcoholic fatty pancreas disease (NAFPD) is estimated as 2-46% among patients without known pancreatic diseases. An association between NAFPD and non-alcoholic fatty liver disease (NAFLD) has been proposed, as well as an association between NAFPD and pancreatic exocrine insufficiency (PEI). PATIENTS AND METHODS: Patients with histologically confirmed NAFLD were included in the study. The control group consisted of individuals included in a surveillance screening program. Magnetic resonance imaging (MRI) of the pancreas was performed in all patients and fat measurement was made using 2-point Dixon imaging. Fecal elastase-1 (FE-1) was performed to evaluate pancreatic exocrine function. Additionally, a 13C-mixed triglyceride breath test (13 C-MTG-BT) was performed in patients with FE-1 < 200 µg/g. RESULTS: Imaging signs of NAFPD were present in 17 (71%) patients; 11 (85%) from the NAFLD group and 6 (55%) from the control group. FE-1 < 200 µg/g was found in six (25%) patients (four in the NAFLD group and two in the control group); however, none of them had clinical symptoms of PEI. Therefore, in five out of six patients with low FE-1, a 13C-MTG-BT was performed, showing normal results (>20.9%) in all tested patients. Furthermore, the serum nutritional panel was normal in all patients with low FE-1. A systematic review identified five studies relevant to the topic. CONCLUSION: NAFPD was found in 85% of patients with NAFLD and in 55% of control patients. We did not diagnose PEI in either group. A literature review showed PEI in 9-56% of patients with NAFPD.
Subject(s)
Exocrine Pancreatic Insufficiency , Non-alcoholic Fatty Liver Disease , Pancreatic Diseases , Humans , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/diagnostic imaging , Pilot Projects , Pancreatic Diseases/diagnosis , Pancreatic Diseases/diagnostic imaging , Exocrine Pancreatic Insufficiency/diagnosis , Exocrine Pancreatic Insufficiency/etiology , Pancreas/pathologyABSTRACT
INTRODUCTION: Nutritional deficiencies, including fat-soluble vitamins and minerals have been detected in many autoimmune diseases, including those involving the digestive system, but have yet to be assessed in autoimmune pancreatitis (AIP). The aim of the present study was to determine the prevalence of micronutrient deficiencies in patients with AIP as well as to investigate their relationship with relapse. PATIENTS AND METHODS: We retrospectively analysed medical records of patients treated for AIP. Demographic and clinical data were collected. RESULTS: One hundred patients were included in the final analysis. The male-to-female ratio was 2.5:1; median age at diagnosis was 57 years (range 19-85). Median follow-up was 53 months, and during this time, 38% of patients suffered from at least one micronutrient deficiency. The most prevalent micronutrient deficiencies were vitamin D (16.1%) and zinc (25.5%). Relapse was observed in 37% of the AIP patients. Initial analysis showed that AIP relapse was associated with any micronutrient deficiency as well as zinc and vitamin D deficiency, but after stratifying for AIP type 1 and adjusting for PEI and elevated IgG4 levels, the association ceased to be statistically significant. CONCLUSION: Zinc and vitamin D deficiencies may be common in patients with AIP, indicating that these micronutrients might play a role in the natural course of AIP. Importantly, any micronutrient deficiency may be prevalent even in the light of treated PEI, which emphasizes the potential of micronutrients as an additional tool in the workup and follow-up of AIP patients.
Subject(s)
Autoimmune Diseases , Autoimmune Pancreatitis , Malnutrition , Vitamin D Deficiency , Humans , Male , Female , Young Adult , Adult , Middle Aged , Aged , Aged, 80 and over , Micronutrients , Retrospective Studies , Vitamins/therapeutic use , Autoimmune Diseases/epidemiology , Autoimmune Diseases/drug therapy , Zinc/therapeutic use , RecurrenceABSTRACT
BACKGROUND: Pre-emptive resection for intraductal papillary mucinous neoplasm (IPMN) aims to reduce the risk before invasive transformation has taken place. Pancreatic resections are highly associated with major morbidity and mortality. Long-term overall survival (OS) after resection for invasive IPMN (inv-IPMN) in early stages is favorable. Comparison of long-term OS for resected non-invasive IPMN and early staged inv-IPMN is poorly delineated. This study aims to compare outcomes for resected non-invasive IPMN and T1-staged inv-IPMN. METHODS: All patients ≥18 years of age resected for IPMN up to stage T1 at Karolinska University Hospital between 2008 and 2020 were included. Two-year OS were compared between groups by chi-squared test, and 5-year OS was estimated using Kaplan-Meier method. Covariates associated with death was assessed in multivariable Cox regression model. RESULTS: We included 284 patients, 264 (93%) non-invasive IPMN and 20 (7%) T1-staged inv-IPMN. Dysplasia of low grade (LGD) and high grade, i.e., tumor in situ (Tis) were present in 190 (67%) and 75 (26%) patients respectively. The 2-year OS for the entire cohort was 96%, and there were no differences between non-invasive and inv-IPMN (96% vs 92%, p = 0.203), nor between IPMN with LGD and Tis-T1b-staged IPMN (96% vs 95%, p = 0.734). CONCLUSION: Two thirds of the specimen from pre-emptive resections were of LGD and did not involve superior OS than in situ or early cancer. Due to high complication burden, efforts should be made to avoid resection when LGD is probable and rather identify more accurate predictors for surgery.
Subject(s)
Carcinoma, Pancreatic Ductal , Pancreatic Intraductal Neoplasms , Pancreatic Neoplasms , Humans , Carcinoma, Pancreatic Ductal/pathology , Pancreatic Intraductal Neoplasms/surgery , Retrospective Studies , Pancreatic Neoplasms/pathology , Pancreatectomy/methodsABSTRACT
INTRODUCTION: Most patients with chronic pancreatitis (CP) develop pancreatic exocrine insufficiency (PEI) over the course of the disease. PEI may lead to hyperoxaluria and development of urinary oxalate stones. It has been postulated that the patients with CP may be at increased risk of kidney stone formation, but the data is scarce. We aimed to estimate incidence and risk factors for nephrolithiasis in a Swedish cohort of patients with CP. PATIENTS AND METHODS: We performed retrospective analysis of an electronical medical database of patients diagnosed with definite CP during 2003-2020. We excluded patients <18 years of age, those with missing relevant data in medical charts, patients with probable CP (according to the M-ANNHEIM classification system) and those in whom kidney stones were diagnosed before CP diagnosis. RESULTS: Some 632 patients with definite CP were followed over a median of 5.3 (IQR 2.4-6.9) years. There were 41 (6.5%) patients diagnosed with kidney stones, of whom 33 (80.5%) were symptomatic. Comparing to patients without kidney stones, patients with nephrolithiasis were older, with median age of 65 (IQR 51-72) years, and a male predominance (80% vs 63%). Cumulative incidence of kidney stones was 2.1%, 5.7%, 12.4% and 16.1% at 5, 10, 15, and 20 years after CP diagnosis, respectively. Multivariable cause-specific Cox regression analysis revealed PEI as independent risk factor for nephrolithiasis (adjusted HR 4.95, 95%CI 1.65-14.84; p = 0.004). Another risk factors were increase in BMI (aHR 1.16 95% CI 1.04-1.30; p = 0.001 per unit increment), and a male sex (4.51, 95% CI 1.01-20.3, p = 0.049). CONCLUSION: PEI and increase in BMI are risk factors for kidney stone development in patients with CP. Male CP patents are particularly at increased risk of nephrolithiasis. This should be taken into consideration in general clinical approach to raise awareness among patients and medical workers.
Subject(s)
Exocrine Pancreatic Insufficiency , Kidney Calculi , Pancreatitis, Chronic , Male , Humans , Middle Aged , Aged , Female , Retrospective Studies , Pancreatitis, Chronic/complications , Pancreatitis, Chronic/epidemiology , Exocrine Pancreatic Insufficiency/complications , Exocrine Pancreatic Insufficiency/epidemiology , Risk Factors , Kidney Calculi/complications , Kidney Calculi/epidemiologyABSTRACT
BACKGROUND: Post-pancreatitis diabetes mellitus (PPDM) is a common consequence of chronic pancreatitis (CP). We aimed to determine the incidence and predictors of PPDM after CP onset, as well as complications and antidiabetic therapy requirements, in a high-volume tertiary center. METHODS: We did a cohort study with retrospectively collected data from patients with definite CP seen at the Karolinska University Hospital between January 1999 and December 2020. Cause-specific Cox regression analysis was used to assess PPDM predictors. To estimate risk of complications and need for therapy the Fine-Gray subdistribution hazard model was employed, accounting for death as a competing risk. RESULTS: We identified 481 patients with CP. The cumulative incidence of PPDM was 5.1%, 13.2%, 27.5% and 38.9% at 5, 10, 15 and 20 years, respectively. Compared to CP patients without diabetes, patients with PPDM were predominantly male (55% vs. 75%), had more frequently alcoholic etiology (44% vs. 62%) and previous acute pancreatitis. The only independent predictor of PPDM was presence of pancreatic calcifications (aHR = 2.45, 95% CI 1.30-4.63). Patients with PPDM had higher rates of microangiopathy (aSHR = 1.59, 95% CI 1.02-2.52) and infection (aSHR = 4.53, 95% CI 2.60-9.09) compared to CP patients who had type 2 diabetes (T2DM). The rate of insulin use was three-fold higher, whereas metformin use rate was two-fold higher in the same comparison. CONCLUSIONS: Patients with PPDM have a higher frequency of clinically significant complications and were more commonly prescribed insulin and metformin, suggesting a more aggressive phenotype than that of T2DM. Greater PPDM awareness is needed to optimize disease management.
Subject(s)
Diabetes Mellitus, Type 2 , Insulins , Metformin , Pancreatitis, Chronic , Male , Female , Humans , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/epidemiology , Cohort Studies , Retrospective Studies , Acute Disease , Pancreatitis, Chronic/complications , Pancreatitis, Chronic/diagnosis , Pancreatitis, Chronic/epidemiology , Metformin/therapeutic useABSTRACT
INTRODUCTION: Although abdominal pain is the most prevalent and disabling symptom in patients with chronic pancreatitis (CP), there are also patients who have painless CP. PATIENTS AND METHODS: We performed a retrospective analysis of patients with a diagnosis of CP. A total of 279 patients with definite CP with completed demographic and clinical data were included in the final analysis. RESULTS: There were 75 (26.9%) patients with painless CP. These patients had a significantly higher mean age at diagnosis, 61.7 years, than the 52.5 years of patients with pain (p < 0.001). Painless and painful CP had similar rates of diabetes mellitus (DM) (28.4% vs. 31.6%) and pancreatic exocrine insufficiency (PEI) (50.0% vs. 52.3%). Painless CP had lower rates of alcoholic etiology, 36.0%, than the 52.5% in painful CP (p < 0.05). Patients older than 55 at the time of CP diagnosis were associated with painless CP with an adjusted odds ratio (aOR) of 3.27 [95% confidence interval (CI): 1.62-6.60]. Alcoholic etiologies were not associated with painless CP, aOR of 0.51 (95% CI: 0.25-0.91). CONCLUSION: Patients with painless CP had a significantly higher mean age than patients with painful CP and increased aOR for those older than 55 at CP diagnosis. Painless and painful CP patients had similar rates of DM and PEI, confirming the necessity of routine follow up in all patients with CP.
Subject(s)
Exocrine Pancreatic Insufficiency , Pancreatitis, Chronic , Humans , Middle Aged , Retrospective Studies , Pancreatitis, Chronic/complications , Pancreatitis, Chronic/epidemiology , Abdominal Pain/epidemiology , Abdominal Pain/etiology , Exocrine Pancreatic Insufficiency/epidemiology , Exocrine Pancreatic Insufficiency/etiology , Odds RatioABSTRACT
INTRODUCTION: Primary sclerosing cholangitis (PSC) is a chronic, cholestatic liver disease that is characterized by an inflammatory and fibrotic process affecting bile ducts which eventually develops into liver cirrhosis and liver failure. The aim of this study was to investigate serum IgG subclass distribution in patients with PSC and its possible association with PSC outcomes. PATIENTS AND METHODS: We performed a retrospective analysis of 181 patients who had been diagnosed with PSC between January 1970 and December 2015 and followed at our outpatient clinic. Their demographic, immunological, and clinical characteristics were recorded and analyzed. RESULTS: This study included 181 patients with PSC (120 males, 61 females). There was no association between IgGs and the development of autoimmune hepatitis, cirrhosis, cholangiocarcinoma, liver transplantation, inflammatory bowel disease, and colectomy. Patients with elevated IgG4 had statistically significant higher rates of cholangitis (p = 0.02) and endoscopic retrograde cholangiopancreatography (ERCP) (p = 0.009). High IgG4 values were observed in nine patients who underwent ERCP. In these nine patients, on average, IgG4 was evaluated 5 years after ERCP (min 3 days, max 11 years). Subanalysis considering only IgG4 values evaluated before ERCP showed no significant difference but remains significant if we consider IgG4 values after ERCP. CONCLUSION: Elevated IgG4 in our study showed a possible association with higher rates of cholangitis and ERCP among patients with primary sclerosing cholangitis. It seems that IgGs may be a useful tool for the prediction of outcomes in patients with PSC. A prospective study is necessary, especially to study the trends of IgGs values during disease as well as the role of possible seroconversion.