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Background: Several different scoring systems have been developed to predict post-pancreatectomy complications. Currently used inflammatory markers are of only limited value in predicting complications after pancreatic surgery. Plasma soluble urokinase plasminogen activator receptor (P-suPAR) is a prognostic biomarker associated with different inflammatory conditions. The aim of this study was to investigate P-suPAR levels before and after pancreatic surgery., Methods: One hundred and seventy-six patients evaluated for pancreatic surgery due to suspected malignant or premalignant lesion were recruited for this study at Tampere University Hospital between 2016 and 2021. P-suPAR was analyzed before the planned operation and on postoperative days (PODs) one and three., Results: One hundred and thirty-three patients [median age 67 (range 33-84) years, 50 % male] underwent a pancreatic surgery procedure. Compared to preoperative values [median 3.7 (IQR 3.1-4.7) ng/mL], P-suPAR was significantly lower on PODs 1 [3.2 (2.5-3.9) ng/mL; p < 0.001] and 3 [3.2 (2.7-4.1) ng/mL; p < 0.001]. P-suPAR on POD 1 was significantly lower in patients with postoperative pancreatic fistula (POPF) [2.6 (2.1-3.4) ng/mL] than in patients with no POPF [3.2 (2.6-3.8) ng/mL; p = 0.007]. Similar decreases in P-suPAR values were seen in patients with postoperative acute pancreatitis (POAP) and surgical site infection (SSI)., Conclusions: After pancreatic surgery, P-suPAR level on POD 1 is significantly lower in patients with POPF, POAP or SSI. P-suPAR is decreased after pancreatic resection in all patients. This type of postoperative P-suPAR profile has not previously been described, and may reflect the compensatory anti-inflammatory reaction following the initial systemic inflammatory reaction caused by surgical trauma., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Only 3-5% of heavy alcohol users develop acute alcohol pancreatitis (AAP). This suggests that additional triggers are required to initiate the inflammatory process. Genetic susceptibility contributes to the development of AAP, and SPINK1 mutation is a documented risk factor. We investigated the prevalence of the SPINK1(N34S) mutation in patients with AAP compared to heavy alcohol users who had never suffered an episode of pancreatitis. Blood samples for the mutational analysis from patients with first episode ( n = 60) and recurrent AAP ( n = 43) and from heavy alcohol users without a history of AAP ( n = 98) as well as from a control population ( n = 1914) were obtained. SPINK1 mutation was found in 8.7% of the patients with AAP. The prevalence was significantly lower in healthy controls (3.4%, OR 2.72; 1.32-5.64) and very low in alcoholics without pancreatitis (1.0%, OR 9.29; 1.15-74.74). In a comparison adjusted for potential cofounders between AAP patients and alcoholics, SPINK1 was found to be an independent marker for AAP. The prevalence of the SPINK1 mutation is overrepresented in AAP patients and very low in alcoholics without pancreatitis. This finding may play a role in understanding the variable susceptibility to AAP found in heavy alcohol users.

Endoscopic retrograde cholangiopancreatography (ERCP) is the primary method for treating cholestasis and biliary tract gallstones. Although noninvasive imaging has replaced ERCP in diagnostics, ERCP remains the mainstay in collecting diagnostic specimens from the biliary tract. ERCP carries a risk of post-ERCP pancreatitis, which can vary from mild to life-threatening. Difficult cannulation is the most important risk factor for pancreatitis. Careful patient selection and adequate endoscopy training are the foundation of safe ERCP practice. Current evidence supports the routine use of prophylactic rectal NSAID in all patients to prevent post-ERCP pancreatitis.

Background: Endoscopic retrograde cholangiopancreatography (ERCP) is a frequent procedure in elderly patients., Aims: We aimed to determine the safety and efficacy of acute ERCP in older patients., Methods: A prospectively managed, hospital-based registry containing all ERCP procedures and complications at a tertiary referral center was used to form the study population, which consisted of consecutive elderly (≥65 years) patients undergoing acute ERCP during the 5-year study period. Indications, details, outcome, and complications of the procedure were analyzed in relation to patient age, gender, and co-morbidities., Results: A total of 480 elderly patients (median age 78; range 65-97; 48 % men) underwent 531 ERCPs during the study period. The most common indications were bile duct stones (56.1 %) and biliary obstruction caused by malignancy (33.7 %). Successful stone extraction was achieved in 72.8 %, and with an additional, planned ERCP in 96.6 % of the patients. Post-ERCP complications developed in 3.4 % of the patients. These included pancreatitis in 1.7 %, hemorrhage in 0.6 %, and duodenal perforation in 0.2 % of the patients. One of these (0.2 %) was considered severe as this patient required invasive treatments and prolonged hospital stay. The risk of complications was associated with chronic obstructive pulmonary disease and difficult cannulation. Procedure-related mortality was zero, but overall 30-day mortality was 10 %, being 24 % in the patients with malignancy., Conclusions: ERCP can be safely and efficaciously performed on elderly patients. The high mortality should be taken into consideration when selecting therapeutic options.

Background: Alcohol abuse constitutes a risk factor for acute pancreatitis and liver cirrhosis, and cirrhosis in turn may delay the recovery from pancreatitis. We evaluated the occurrence and significance of liver fibrosis or cirrhosis in patients with acute pancreatitis by applying transient elastography (TE)., Methods: TE was carried out in 78 patients with acute pancreatitis. Comparisons were made to the severity and recurrence of pancreatitis, to biological markers for fibrosis (APRI test), alcohol intake (AST/ALT ratio, AUDIT), and prothrombin time (TT-SPA). A cut-off value of ≥7.5 kilopascals (kPa) was set for increased liver stiffness, and ≥10 kPa for significant fibrosis., Results: The aetiology of pancreatitis was alcohol intake in 62 patients, gallstones in 11, idiopathic in 3, tumour in 1 and medication in 1. TE was successful in 64 out of 78 patients. The median TE value was 6.5 kPa (range 2.5-61.1); 22 (35%) had values ≥7.5 kPa and 7 (11%) ≥10 kPa. Values ≥7.5 were associated with older age, higher APRI ratio, and lower TT-SPA. It did not predict the length of hospitalization or the recurrence of pancreatitis. Increased AST/ALT ratio was associated with high TE values, whereas AUDIT values were not. Values ≥10 kPa seemed to indicate manifest cirrhosis, hepatitis or subsequent development of diabetes., Conclusions: TE values ≥7.5 kPa did not predict the length of hospital stay or recurrence of pancreatitis but there were some findings of impaired liver function. Values ≥10 kPa may indicate subsequent development of diabetes and a more severe course of acute pancreatitis., (Copyright © 2014 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Objectives: Soft pancreas is considered as a factor for pancreatitis after pancreaticoduodenectomy, which in turn constitutes a high risk for local complications. The aim was to analyze the proportion of different cell types in the cut edge of pancreas (CEP) in relation to postoperative pancreatitis and other complications after pancreaticoduodenectomy., Methods: Data from postoperative follow-up was collected on 40 patients who had undergone pancreaticoduodenectomy. Positive urine trypsinogen-2, an early detector of pancreatitis, was checked on days 1 to 6 after operation. Drain amylase was measured on postoperative day 3. Anastomotic leakages, delayed gastric emptying, and other complications were registered. The areas of different cell types were calculated from the entire hematoxylin-eosin-stained section of CEP., Results: High frequency of acinar cells in the CEP significantly increased positive urine trypsinogen-2 days, drain amylase values, and delayed gastric emptying. In a subgroup of patients with more than 40% acini in the CEP, there were significantly more postoperative complications. Increased fibrosis correlated with a small number of positive urine trypsinogen-2 days and postoperative complications., Conclusions: A large number of acinar cells in the CEP increases, whereas extensive fibrosis in the CEP decreases, the risk for postoperative complications after pancreaticoduodenectomy. These results emphasize the importance of acini in the development of postoperative complications.

Mechanistic studies of acute pancreatitis require animal models because clinical material is generally not available during the early phases of the disease. Here we describe a protocol to induce biliary pancreatitis by retrogradely infusing bile acids into the pancreatic duct of anesthetized mice. The resulting model replicates events believed to be responsible for the onset of clinical biliary (i.e., gallstone) pancreatitis and creates highly reproducible pancreatitis with a severity that depends on the concentration of infused bile acid. Pancreatitis reaches its maximal level of severity within 24 h of induction, and it resolves over the subsequent week. This protocol enables the investigator to use genetically modified strains of mice, and it requires only relatively simple and easily learned techniques of small animal surgery. With practice and gentle technique, the surgery (from induction of anesthesia to completion of the infusion) can be completed within 25 min per animal.

Background & Aims: The mechanisms by which reflux of bile acids into the pancreas induces pancreatitis are unknown. We reasoned that key events responsible for this phenomenon might be mediated by Gpbar1, a recently identified and widely expressed G-protein-coupled, cell surface bile acid receptor., Methods: Acute pancreatitis was induced in wild-type and Gpbar1(-/-) mice by either retrograde ductal infusion of taurolithocholic acid-3-sulfate (TLCS) or supramaximal secretagogue stimulation with caerulein. In vitro experiments were performed in which acini obtained from wild-type and Gpbar1(-/-) mice were exposed to either submicellar concentrations of TLCS (200-500 microM) or a supramaximally stimulating concentration of caerulein (10 nM)., Results: Gpbar1 is expressed at the apical pole of acinar cells and its genetic deletion is associated with reduced hyperamylasemia, edema, inflammation, and acinar cell injury in TLCS-induced, but not caerulein-induced, pancreatitis. In vitro, genetic deletion of Gpbar1 is associated with markedly reduced generation of pathological calcium transients, intracellular activation of digestive zymogens, and cell injury when these responses are induced by exposure to TLCS, but not when they are induced by exposure to caerulein., Conclusions: Gpbar1 may play a critical role in the evolution of bile-acid-induced pancreatitis by coupling exposure to bile acids with generation of pathological intracellular calcium transients, intra-acinar cell zymogen activation, and acinar cell injury. Acute biliary pancreatitis may be a "receptor-mediated" disease and interventions that interfere with Gpbar1 function might prove beneficial in the treatment and/or prevention of biliary acute pancreatitis.

Protease-activated receptor-2 (PAR2) is a 7-transmembrane G-protein-coupled tethered ligand receptor that is expressed by pancreatic acinar and ductal cells. It can be physiologically activated by trypsin. Previously reported studies (Namkung, W., Han, W., Luo, X., Muallem, S., Cho, K. H., Kim, K. H., and Lee, M. G. (2004) Gastroenterology 126, 1844-1859; Sharma, A., Tao, X., Gopal, A., Ligon, B., Andrade-Gordon, P., Steer, M. L., and Perides, G. (2005) Am. J. Physiol. 288, G388-G395) have shown that PAR2 activation exerts a protective effect on the experimental model of pancreatitis induced by supramaximal secretagogue (caerulein) stimulation. We now show that PAR2 exerts a worsening effect on a different model of experimental pancreatitis, i.e. one induced by retrograde pancreatic ductal infusion of bile salts. In vitro studies using freshly prepared pancreatic acini show that genetic deletion of PAR2 reduces bile salt-induced pathological calcium transients, acinar cell injury, and activation of c-Jun N-terminal kinase, whereas genetic deletion of PAR2 has the opposite or no effect on these pancreatitis-related events when they are elicited, in vitro, by caerulein stimulation. Studies employing a combination of trypsin inhibition and activation of PAR2 with the activating peptide SLIGRL show that all these differences indeed depend on the activation of PAR2. These studies are the first to report that a single perturbation can have model-specific and opposite effects on pancreatitis, and they underscore the importance of performing mechanistic pancreatitis studies using two dissimilar models of the disease to detect idiosyncratic, model-specific events. We suggest PAR2 activation exerts a worsening effect on the severity of clinical pancreatitis and that interventions interfering with PAR2 activation may be of benefit in the treatment of patients with severe pancreatitis.

Objective: Most mechanistic studies of pancreatitis in mice employ the secretagogue-induced model. The currently reported studies were designed to develop an alternative, and possibly more clinically relevant, mouse model of pancreatitis., Design: Na-taurocholate (10-50 microl, 1-5%) in saline, or saline alone, was retrogradely infused into the mouse pancreatic duct. The animals were killed 6-24 hours later and the severity of pancreatitis in the pancreatic head and tail was examined by quantitating hyperamylasemia, pancreatic edema, acinar cell necrosis, and pancreatic inflammation. In addition, intrapancreatic activation of trypsinogen, generation of IL-6, intrapulmonary sequestration of neutrophils, and alterations in lung compliance were evaluated. The effects of Na-taurocholate on in-vitro acinar cell calcium transients, viability, and trypsinogen activation were examined., Results: Little or no evidence of pancreatitis was observed in mice infused with saline alone or in the tail of pancreata removed from animals infused with Na-taurocholate. In the head of the pancreas, evidence of pancreatitis was observed 12-24 hours after infusion of 20-50 microl 2-5% Na-taurocholate and the earliest morphological changes involved terminal duct and acinar cells. Intrapancreatic trypsin activity was transiently elevated within 5 minutes of Na-taurocholate infusion and pancreatic IL-6 levels were elevated 24 hours later. Under in-vitro conditions, Na-taurocholate triggered pathological acinar cell calcium transients, cell death, and calcium-dependent trypsinogen activation., Conclusion: This clinically relevant model of acute biliary pancreatitis yields reproducible results and its severity can be easily manipulated. It is ideally suited for use in mechanistic studies employing genetically modified mouse strains.

Advances in our understanding of total pancreatectomy with islet autotransplantation (TPIAT) have been made. We aimed to define indications and outcomes of TPIAT. Expert physician-scientists from North America, Asia, and Europe reviewed the literature to address six questions selected by the writing group as high priority topics. A consensus was reached by voting on statements generated from the review. Consensus statements were voted upon with strong agreement reached that (Q1) TPIAT may improve quality of life, reduce pain and opioid use, and potentially reduce medical utilization; that (Q3) TPIAT offers glycemic benefit over TP alone; that (Q4) the main indication for TPIAT is disabling pain, in the absence of certain medical and psychological contraindications; and that (Q6) islet mass transplanted and other disease features may impact diabetes mellitus outcomes. Conditional agreement was reached that (Q2) the role of TPIAT for all forms of CP is not yet identified and that head-to-head comparative studies are lacking, and that (Q5) early surgery is likely to improve outcomes as compared to late surgery. Agreement on TPIAT indications and outcomes has been reached through this working group. Further studies are needed to answer the long-term outcomes and maximize efforts to optimize patient selection. [ABSTRACT FROM AUTHOR]

Objectives:Chronic pancreatitis (CP) is a multifaceted disease associated with several risk factors and a complex clinical presentation. We established the Scandinavian Baltic Pancreatic Club (SBPC) Database to characterise and study the natural history of CP in a Northern European cohort. Here, we describe the design of the database and characteristics of the study cohort. Methods:Nine centres from six different countries in the Scandinavian-Baltic region joined the database. Patients with definitive or probable CP (M-ANNHEIM diagnostic criteria) were included. Standardised case report forms were used to collect several assessment variables including disease aetiology, duration of CP, preceding acute pancreatitis, as well as symptoms, complications, and treatments. The clinical stage of CP was characterised according to M-ANNNHEIM. Yearly follow-up is planned for all patients. Results:The study cohort comprised of 910 patients (608 men: 302 women; median age 58 (IQR: 48–67) years with definite 848 (93%) or probable CP 62 (7%). Nicotine (70%) and alcohol (59%) were the most frequent aetiologies and seen in combination in 44% of patients. A history of recurrent acute pancreatitis was seen in 49% prior to the development of CP. Pain (69%) and exocrine pancreatic insufficiency (68%) were the most common complications followed by diabetes (43%). Most patients (30%) were classified as clinical stage II (symptomatic CP with exocrine or endocrine insufficiency). Less than 10% of the patients had undergone pancreatic surgery. Conclusion:The SBPC database provides a mean for future prospective, observational studies of CP in the Northern European continent. [ABSTRACT FROM AUTHOR]

Aims After the first acute alcoholic pancreatitis (AAP), active repeated brief interventions (BIs) have been shown to protect against recurrent acute pancreatitis (RAP). However, in daily hospital practice the treatment of alcohol problems varies. Our aim was to study BIs performed in the clinic during AAP and whether this prevents from future RAP episodes. Methods Data on all patients discharged between 10/2010 and 10/2012 with acute pancreatitis as the primary diagnosis were obtained from the hospital database. Patients with the first attack of AAP were included in the study. Documented BIs during hospitalization for AAP and RAP and the development of RAP and chronic pancreatitis during median (range) follow-up of 4.2 (0.2–6.1) years were analyzed. Patients were also contacted with a mailed questionnaire. Results A total of 74 patients with first AAP during the study period were included. Of these, 32% developed RAP during follow-up. Of the patients, 72% received a documented BI during initial hospitalization, with no difference between patients who later did or did not develop RAP (71 vs. 72%; ns). Younger age (OR = 0.96, 95% CI = 0.92–1.00) and higher AUDIT points (P = 0.044; OR = 5.6; 95% CI = 1.02–30.9 for ≥20 AUDIT points) were associated with RAP. AUDIT test had 70% sensitivity and 71% specificity at a cut-off value of 20 points for predicting RAP. Conclusions Only 72% of the patients received a documented BI during the initial hospitalization for AAP. The in-hospital BI as such did not prevent the development of RAP. Young patients with AUDIT points ≥20 are especially at high risk for developing RAP and should be included in a more intense follow-up care program to maximize prevention. Short summary During hospitalization for acute alcoholic pancreatitis (AAP), one third of the patients did not receive brief interventions (BIs). The in-hospital BI by itself was not sufficient enough to prevent disease recurrence in follow-up of 4 years. Young age and higher AUDIT-points were significant risk factors for recurrent attacks of AAP. [ABSTRACT FROM AUTHOR]

Objective: The long-term morphological changes induced by a single episode of alcoholic pancreatitis are not known. Our aim was to study these morphological changes in secretin-stimulated magnetic resonance cholangiopancreatography (S-MRCP) after the first episode of alcohol-associated acute pancreatitis and to evaluate the risk factors and possible protective factors potentially associated with later chronic findings. We have previously reported 2-year follow-up results in pancreatic morphology. This study extends the follow-up to 9 years. Patients and Methods: In this prospective follow-up study, S-MRCP imaging was performed for 44 (41 M, 3 F; mean age, 46 (25-68) years) patients after their first episode of alcohol-associated pancreatitis. Pancreatic morphology was evaluated at 3 months and at 2, 7, and 9 years after hospitalization. Recurrent attacks of pancreatitis were studied and pancreatic function was monitored by laboratory tests. Patients' alcohol consumption was evaluated with questionnaires, laboratory markers, and self-estimated alcohol consumption via interview. Smoking and body mass index were annually recorded. Results: At 3 months, 32 % of the patients had normal findings in S-MRCP, 52 % had acute, and 16 % had chronic changes. At 7 years, S-MRCP was performed on 36 patients with normal findings in 53 %, the rest (47 %) having chronic findings. Pancreatic cyst was present in 36 %, parenchymal changes in 28 %, and atrophy in 28 % of the cases. There were no new changes in the pancreas in the attending patients between 7 and 9 years (18 patients). Of the patients with only acute findings at 3 months, 60 % resolved to normal in 7 years, but the rest (40 %) showed chronic changes later on. The initial attack was mild in 65 %, moderate in 25 %, and severe in 10 % of the patients. Patients with mild first attack had fewer chronic changes at 7 years compared to patients with moderate or moderate and severe together ( p = 0.03, p = 0.01). Of the patients in the seventh year of S-MRCP, 22 % had suffered a recurrent episode of acute pancreatitis (mean, 22 (2-60) months) and 11 % had a clinical diagnosis of chronic pancreatitis. At 7 years, 88 % of the patients with recurrences had chronic findings in S-MRCP versus 36 % with nonrecurrent pancreatitis ( p = 0.02). Six (17 %) patients abstained from alcohol throughout follow-up (mean, 8.7 (7-9.1) years), but even one of these developed pancreatic atrophy. Out of the non-abstinent patients who did not suffer recurrences, 4/22 (18 %) had developed new findings during at follow-up S-MRCP (NS). In univariate analysis, heavy smoking showed no correlation with increased chronic changes compared to nonsmoking. Conclusions: Morphological pancreatic changes increase with recurrent episodes of acute pancreatitis. Patients with mild first attack have fewer chronic changes in the pancreas in the long term. However, even a single episode of acute alcoholic pancreatitis may induce chronic morphological changes in long-term follow-up. [ABSTRACT FROM AUTHOR]

Aims: To determine the recurrence of pancreatitis and subsequent pancreatic function in patients who stop drinking after the first episode of alcohol-associated pancreatitis. Methods: Of a total of 118 patients suffering from their first alcohol-associated pancreatitis, 18 (all men, age median 47 (27-71) years) met the inclusion criterion for abstinence during follow-up. The criterion for abstinence was alcohol consumption <24 g per 2 months (self-estimated), which is in line with questionnaires eliciting alcohol consumption and dependency (Alcohol Use Disorders Identification Test < 8 and Short Alcohol Dependence Data < 9). Recurrent attacks of acute pancreatitis were studied. Smoking, body mass index and laboratory tests detecting heavy consumption of alcohol were recorded. Blood and faecal tests were studied to assess endocrine and exocrine pancreatic function. Results: During a mean follow-up time of 5.15 (1.83-9.13) years and a total of 92.7 patient-years, there were no recurrent attacks of acute pancreatitis among the 1 8 abstainers. Two patients had diabetes prior to and one was diagnosed immediately after the first episode of acute pancreatitis. One patient had impaired glucose metabolism at 2 years. Two patients had low insulin secretion in glucagon-C-peptide test, one at 4 years and the other at 5 years. Only one patient (6%) maintained low elastase-1 activity during the abstinence follow-up. Of the 100 non-abstainers, 34% had at least one recurrence during the follow-up. Conclusion: Regardless of the mediator mechanisms of acute alcoholic pancreatitis, abstinence after the first episode pmtects against recurrent attacks. Pancreatic dysfunction is also rare among abstinent patients. [ABSTRACT FROM AUTHOR]

Background & Aims: The mechanisms by which reflux of bile acids into the pancreas induces pancreatitis are unknown. We reasoned that key events responsible for this phenomenon might be mediated by Gpbar1, a recently identified and widely expressed G-protein−coupled, cell surface bile acid receptor. Methods: Acute pancreatitis was induced in wild-type and Gpbar1 −/− mice by either retrograde ductal infusion of taurolithocholic acid-3-sulfate (TLCS) or supramaximal secretagogue stimulation with caerulein. In vitro experiments were performed in which acini obtained from wild-type and Gpbar1 −/− mice were exposed to either submicellar concentrations of TLCS (200−500 μM) or a supramaximally stimulating concentration of caerulein (10 nM). Results: Gpbar1 is expressed at the apical pole of acinar cells and its genetic deletion is associated with reduced hyperamylasemia, edema, inflammation, and acinar cell injury in TLCS-induced, but not caerulein-induced, pancreatitis. In vitro, genetic deletion of Gpbar1 is associated with markedly reduced generation of pathological calcium transients, intracellular activation of digestive zymogens, and cell injury when these responses are induced by exposure to TLCS, but not when they are induced by exposure to caerulein. Conclusions: Gpbar1 may play a critical role in the evolution of bile-acid−induced pancreatitis by coupling exposure to bile acids with generation of pathological intracellular calcium transients, intra-acinar cell zymogen activation, and acinar cell injury. Acute biliary pancreatitis may be a “receptor-mediated” disease and interventions that interfere with Gpbar1 function might prove beneficial in the treatment and/or prevention of biliary acute pancreatitis. [Copyright &y& Elsevier]

Objective. Diagnosis of chronic pancreatitis is usually based on symptoms, ductal or parenchymal changes in imaging studies and function tests, but seldom on histology. Because the diagnosis of mild chronic pancreatitis is especially difficult, better tools to distinguish between chronic pancreatitis and normal pancreas are needed. Nowadays, cutting needles as thin as the widely used puncture needles are available. Using resected specimens, our aim was to evaluate whether these ultra-thin needles can take samples for histology that would allow verification of the diagnosis of chronic pancreatitis, with reference to a pancreatic wedge biopsy as the "gold standard". Material and Methods. Fifty patients underwent pancreatic resection for various reasons. Two 20 G needle biopsies (outer diameter 0.8 mm, study biopsies) and a 5×5-mm wedge biopsy (reference biopsies) were taken from the same site of the specimen, avoiding possible neoplastic areas in the specimen. The samples were analyzed for the presence inflammation and fibrosis, both graded 0-3, as well as for any neoplastic changes without knowledge of the medical history, operative findings or final histology. Results. The reference biopsy showed normal tissue in 19 (38%) patients, chronic pancreatitis in 29 (58%) and only mild fibrosis (Grade 1) in 2 (4%) patients. In one patient the needle biopsy was insufficient for analysis. There was agreement between ultra-thin needle histology and the control specimen in 45/49 (92%) patients (correlation coefficient 0.9). Two biopsies of chronic pancreatitis and one mild fibrosis were misclassified as normal tissue, while one chronic pancreatitis biopsy was misclassified as an adenocarcinoma. The sensitivity of needle biopsy for chronic pancreatitis was 89%, specificity 100% and accuracy 94%. Conclusions. Ultra-thin needle histology correlates well with the pancreatic wedge biopsy. Thus, these encouraging results warrant further clinical studies of different grades and types of chronic pancreatitis. [ABSTRACT FROM AUTHOR]

The roles of monocytes/macrophages and their mechanisms of action in the regulation of pancreatitis are poorly understood. To address these issues, we have employed genetically altered mouse strains that either express the human diphtheria toxin receptor (DTR) coupled to the CD11b promoter or have global deletion of TNF-α. Targeted, conditional depletion of monocytes/macrophages was achieved by administration of diphtheria toxin (DT) to CD11b-DTR mice. We show that in the absence of DT administration, pancreatitis is associated with an increase in pancreatic content of Ly-6Chi monocytes/macrophages but that this response is prevented by prior administration of DT to CD11b-DTR mice. DT administration also reduces pancreatic edema and acinar cell injury/necrosis in two dissimilar experimental models of acute pancreatitis (a secretagogue-induced model and a model elicited by retrograde pancreatic duct infusion of sodium taurocholate). In the secretagogue-elicited model, the DT-induced decrease in pancreatitis severity is reversed by adoptive transfer of purified Ly-6Chi monocytes harvested from non-DT-treated CD11b-DTR mice or by the transfer of purified Ly-6Chi monocytes harvested from TNF-α+/+ donor mice, but it is not reversed by the transfer of Ly-6Chi nionocytes harvested from TNF-α-/- donors. Our studies indicate that the Ly-6Chi monocyte subset regulates the severity of pancreatitis by promoting pancreatic edema and acinar cell injury/necrosis and that this phenomenon is dependent upon the expression of TNF-α by those cells. They suggest that therapies targeting Ly-6Chi monocytes and/or TNF-α expression by Ly-6Chi monocytes might prove beneficial in the prevention or treatment of acute pancreatitis. [ABSTRACT FROM AUTHOR]