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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.

Objectives: SuPAR (soluble urokinase-type plasminogen activator receptor) is a biomarker reflecting the inflammatory state of the human body. Earlier studies suggest that urinary suPAR/creatinine ratio levels are elevated in chronic pancreatitis (CP), and that plasma suPAR (P-suPAR) level is elevated in pancreatic cancer (PC). Our aim was to study the levels of P-suPAR in CP in a long-term prospective follow-up setting to explore the possibility of distinguishing between PC and CP., Materials and Methods: Two patient groups were compared. The first group included 83 patients who were prospectively followed up after their first acute alcohol-induced pancreatitis (AAP) for median 7.0 (range 0.3-9.8) years. Twelve patients in this group developed CP during follow-up, and two patients were further excluded from the CP cohort. The second group consisted of 25 patients operated on for suspicion of pancreatic malignancy and final pathological diagnosis of PC. P-suPAR levels were measured and compared within and between these groups., Results: P-suPAR levels remained low during follow-up despite the development of CP. P-suPAR was significantly higher in PC patients [median 3.7 (IQR 3.1-4.4) ng/mL] than in CP patients [2.6 (1.8-3.6) ng/mL]; p  = .014. A cutoff value of 2.8 ng/mL resulted from a ROC curve with area under curve (AUC) of 0.79 (95% CI 0.61-0.97), p  = .009 in differentiation between PC and CP with a sensitivity and a specificity of 88% and 70% respectively., Conclusion: P-suPAR is higher in patients with PC than in patients with CP, and it could thus be used in differentiating between PC and CP.

Background: Soluble urokinase plasminogen activator receptor (suPAR) is a biomarker associated with inflammatory and certain malignancies. Earlier we have shown that plasma suPAR (P-suPAR) predicts severity of acute alcohol-induced pancreatitis (AAP) on admission. Our aim was to investigate whether P-suPAR levels predict AAP recurrences or mortality during long-term follow-up after first AAP., Methods: Eighty-three patients (median age 47.5, range 25-71 years) suffering their first AAP during 2001-2005 were recruited and followed prospectively for 9 years with a median follow-up time of 7.0 (range 0.3-9.8) years. P-suPAR was measured by enzyme-linked immunosorbent assay (ELISA) from the samples taken at follow-up visits. Survival was registered in November 2014., Results: P-suPAR level on admission or after recovery of the first AAP did not predict the recurrence of AAP. However, higher P-suPAR measured after recovery of first AAP (3.6 vs. 2.9 ng/mL) predicted mortality during follow-up period (hazard ratio 1.48, p = .008). Cut-off value for P-suPAR indicating a higher risk for 10-year mortality resulted a value of ≥3.4 ng/mL. When adjusted for other covariates, P-suPAR above cut-off level retained its statistical significance as an independent factor., Conclusions: P-suPAR level on admission or after recovery of the first AAP does not predict the recurrence of AAP during long-term follow-up. However, P-suPAR ≥3.4 mg/mL measured after recovery from first AAP is associated with an increased risk of 10-year mortality as an independent factor. This can be used to detect patients with highest risk after AAP, in order to focus the preventive healthcare actions., (Copyright © 2018. Published by Elsevier B.V.)

Introduction: Survival for pancreatic ductal adenocarcinoma (PDAC) is relatively short even after complete resection. Pancreaticoduodenectomy (PD) carries a high risk for postoperative morbidity, and the effect on quality of life (QoL) is unclear. We aimed to study QoL in PDAC patients undergoing PD., Patients and Methods: Sixty patients with suspected PDAC and planned PD were asked to complete EORTC QoL questionnaires QLQ-C30 and QLQ-PAN26 preoperatively and at 3-6-12-18-24 months postoperatively., Results: 47 PDAC patients who underwent PD (66 (21-84) years, 53% men) were included. Follow-up was completed by 81% (6 months) and 45% (24 months) post-PD. Compared to preoperative level, QoL tended to improve or remained the same in 63% during the follow-up. At three months after PD patients had less hepatic symptoms (decreased by 100%; p < 0.001), pancreatic pain and sexuality symptoms tended to decrease by 33% and global and functional QoL tended to slightly improve. These parameters remained at the achieved level during the longer follow-up. A temporary rising tendency was seen in digestive symptoms at three months but this later reverted to the preoperative level. More altered bowel movements and sexuality symptoms tended to arise during the longer follow-up. A negative correlation was found between reported financial difficulties and length of survival., Conclusions: PD does not worsen the QoL in most of the patients with PDAC. The potentially beneficial effect on QoL is apparent already at three months after surgery. This information may be helpful for the clinician and patient, when deciding on the treatment for PDAC., (Copyright © 2017 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Objective: The objective of the present study was to describe how a specific patient flow analysis with from-to charts can be used in hospital design and layout planning., Background: As part of a large renewal project at a university hospital, a detailed patient flow analysis was applied to planning the musculoskeletal surgery unit (orthopedics and traumatology, hand surgery, and plastic surgery)., Method: First, the main activities of the unit were determined. Next, the routes of all patients treated over the course of 1 year were studied, and their physical movements in the current hospital were calculated. An ideal layout of the new hospital was then generated to minimize transfer distances by placing the main activities with close to each other, according to the patient flow analysis. The actual architectural design was based on the ideal layout plan. Finally, we compared the current transfer distances to the distances patients will move in the new hospital., Results: The methods enabled us to estimate an approximate 50% reduction in transfer distances for inpatients (from 3,100 km/year to 1,600 km/year) and 30% reduction for outpatients (from 2,100 km/year to 1,400 km/year)., Conclusions: Patient transfers are nonvalue-added activities. This study demonstrates that a detailed patient flow analysis with from-to charts can substantially shorten transfer distances, thereby minimizing extraneous patient and personnel movements. This reduction supports productivity improvement, cross-professional teamwork, and patient safety by placing all patient flow activities close to each other. Thus, this method is a valuable additional tool in hospital design.

Background and Aims: The incidence of gallstones and gallbladder sludge is higher in patients after total gastrectomy than in general population. Formation of gallstones after gastrectomy is multifactorial. Here, we investigate the changes in gallbladder and biliary tract functions by cholescintygraphy and monitored changes in cholecystokinin (CCK) release in long-term survivors after total gastrectomy for gastric carcinoma., Material and Methods: Patients had undergone total gastrectomy for gastric carcinoma at least five years ago. The final study population consisted of 25 patients., Results: Eight patients had undergone cholecystectomy before or at the time of gastrectomy. Gallstone formation was observed in seven of the remaining 17 patients during follow-up (41%). Maximum uptake of radioactivity and gallbladder maximum uptake was significantly delayed in the gastrectomy group than in the control group. There was no significant difference in CCK levels after the overnight fasting and at 60 minutes after stimulation among patients with or without stones in situ compared with healthy volunteers, but 30 minutes after the energy-rich drink patients had higher CCK levels than the control group., Conclusions: In gastrectomy patients, technetium isotope visualisation of the gallbladder and time for maximum activity was significantly delayed. This may indicate impaired gallbladder function. On the contrary, CCK release was not impaired.

Background: Data on the prevalence of pancreatic dysfunction after an episode of acute pancreatitis are conflicting. Our aim was to evaluate the natural course of endocrine and exocrine pancreatic function in the long-term follow-up after the first episode of acute alcoholic pancreatitis (AAP)., Methods: A total of 77 patients who survived their first episode of AAP between January 2001 and February 2005 were prospectively followed up for a maximum of 13 years. During the follow-up, patients were repeatedly interviewed and monitored for recurrences, new diabetes, and chronic pancreatitis. The pancreatic function was evaluated repeatedly during the follow-up., Results: Of the patients, 35% had ≥1 recurrent acute pancreatitis (RAP) episodes during the follow-up. New pancreatogenic diabetes developed in 19% of the previously nondiabetic patients, but only in patients with RAP (13/26 vs. 0/42; OR=39; 95% CI, 4.6-327.1). In addition, 55% of the patients developed new prediabetes or diabetes, and even this was more frequent in patients with RAP (86% vs. 42%; OR=8.2; 95% CI, 1.2-54.3). Exocrine dysfunction developed in 24% of the patients and was associated with abnormal findings in the endocrine function (P=0.003). Patients with RAP had a higher overall mortality compared with patients without RAP episodes during the follow-up (36% vs. 13%; HR=4.0; 95% CI, 1.4-11.0)., Conclusions: The risk for pancreatic endocrine dysfunction, pancreatogenic diabetes and mortality increases significantly if the patient has recurrent episodes of AAP. The risk of developing pancreatic dysfunction after AAP should be recognized and pancreatic function should be screened routinely during the years after the first episode of AAP.

Objectives: Systemic levels of soluble urokinase-type plasminogen activator receptor (suPAR) are increased in various inflammatory and infectious diseases. We investigated the activation and prognostic value of plasma suPAR (P-suPAR) in patients experiencing their first acute alcohol pancreatitis (AAP)., Methods: From prospectively collected data, we measured P-suPAR concentrations in 104 patients with AAP during hospitalization and again after discharge., Results: According to the revised Atlanta classification, pancreatitis was moderately severe in 29 (28%) and severe in 6 (6%) patients and these severities were combined for further analysis (non-mild AAP, n = 35; 34%). Median P-suPAR levels were significantly higher in patients with AAP during hospitalization than after discharge (4.8 vs 3.1 ng/mL; P < 0.001) and in non-mild compared to mild AAP (6.2 vs 4.2 ng/mL; P < 0.001). When the analysis was made 1 to 4 days after admission (n = 68), the area under the curve was 0.81 (95% confidence interval, 0.70-0.92). P-suPAR was found to be a better prognostic marker in AAP than C-reactive protein, hematocrit, or creatinine., Conclusions: P-suPAR concentrations are elevated in AAP and correlate with the severity of the disease. These results suggest that P-suPAR may have potential to serve as a novel prognostic marker for AAP severity on admission.

Objectives: The aim of this study was to study whether post-pancreaticoduodenectomy complications (PPDC) in high-risk patients can be reduced with hydrocortisone., Background: Soft pancreas is a well-known risk factor for PPDC. Previously, we have shown that patients with >40% acini in the pancreatic transection line are most prone to PPDC. Recent studies have demonstrated that surgical trauma leads to inflammation of the pancreatic remnant, which precedes PPDC., Methods: On the basis of power analysis, randomized controlled trial (RCT) (Clinicaltrials.gov NCT01460615), 155 patients (February 2011-May 2015) scheduled for pancreaticoduodenectomy were randomized to intravenous (i.v.) treatment with hydrocortisone 100 mg or placebo. All patients received the first dose at the induction of anesthesia. During the operation, the percentage of acini was calculated from pancreatic transection line frozen samples by a pathologist. As planned, only the high-risk patients with >40% acini (n = 62) continued in the study to receive in total 8 doses of randomization-based hydrocortisone/placebo every 8 hours. Primary endpoints were urine trypsinogen positive days and overall complications (Clavien-Dindo III-IV). Postoperative pancreatic fistulas (POPFs), postpancreatectomy hemorrhage (PPH), and delayed gastric emptying (DGE) were also graded., Results: Hydrocortisone treatment did not alter trypsinogen release (2 or more positive days 46% vs 50%), but it significantly reduced overall complications compared with placebo in the high-risk patients (18% vs 41%; P < 0.05; Clavien-Dindo III-IV). Also, clinically significant POPF (11% vs 27%), PPH (14% vs 24%), and DGE (29% vs 44%) tended to be lower in the hydrocortisone group. Ninety-day mortality was zero., Conclusions: This RCT shows that in high-risk patients, overall PPDC can be significantly reduced with hydrocortisone treatment. Inflammation may be an important mediator of PPDC.

Background: Benign biliary strictures (BBS) are primarily treated endoscopically with covered self-expandable metal stents (CSEMS). Biodegradable biliary stents (BDBS) may be the future of endoscopic therapy of BBS. The aim was to assess the expression of proteins related to tissue healing in BBS compared with the intact bile duct (BD), and to study the protein expression after therapy with CSEMS or BDBS., Methods: Pigs with ischemic BBS were endoscopically treated either with BDBS or CSEMS. Samples were harvested from pigs with intact BD (n = 5), untreated BBS (n = 5), and after six months of therapy with BDBS (n = 4) or CSEMS (n = 5) with subsequent histologic analysis. Two-dimensional electrophoresis with protein identification was performed to evaluate protein expression patterns., Results: In BBS, the expression of galectin-2 and annexin-A4 decreased, compared to intact BD. Treatment with biodegradable stents normalized galectin-2 level; with CSEMS therapy it remained low. Transgelin expression of intact BD and BBS remained low after BDBS treatment but increased after CSEMS therapy. Histologic analysis did not show unwanted foreign body reaction or hyperplasia in the BD in either group., Conclusions: The expression of proteins related to tissue healing in BBS is different after treatment with biodegradable stents and CSEMS. Treatment with biodegradable stents may bring protein expression towards what is seen in intact BD. BDBS seem to have a good biocompatibility.

Background: Distinguishing between pancreatic cancer and chronic pancreatitis (CP) is often difficult. Certain (5-6%) CP cases are autoimmune in nature, and these patients respond to corticosteroid treatment, making surgery avoidable. Our aim was to evaluate the incidence of autoimmune pancreatitis (AIP) among patients operated on for a pancreatic mass with a final histology of CP., Patients and Methods: A total of 33 patients were operated on at the Tampere or Helsinki University Hospital for suspicion of cancer, but with final histopathological diagnosis of CP. The median age was 58 (31-81) years; 26 patients (79%) were male. There were 28 pancreaticoduodenectomes and five left pancreatic resections. Surgical specimens were re-evaluated by experienced pathologists, with representative samples chosen for immunohistochemistry Each sample was scored as positive or negative for immunoglobulin G4 (IgG4) independently by two pathologists. Honolulu consensus criteria served for AIP sub-typing., Results: Out of the 33 specimens, 10 (30%) were positive for IgG4. Histopathological re-evaluation of these revealed all to be type 1 AIP., Conclusion: The proportion of AIP, according to IgG4-positive immunohistochemistry and histological re-evaluation, was much higher than expected. This suggests that by focusing on diagnosis of AIP preoperatively, certain patients might be treated with corticosteroids and possibly avoid unnecessary surgery., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Objective: The aim of the present trial was to ascertain whether laparoscopic cholecystectomy (LCC) can prevent recurrent attacks of idiopathic acute pancreatitis (IAP)., Summary: Up to 50% to 75% of IAP may be due to microlithiasis, which is undetectable by conventional imaging methods., Methods: This randomized, prospective trial included 85 patients (39 in the LCC and 46 in the control group) in 8 hospitals in Finland. We included adult patients (over 18 years) with their first attack of IAP. The diagnosis of IAP was based on the exclusion of common etiological reasons for acute pancreatitis (AP), whereafter the patients were randomized into conservative watchful waiting (controls) or LCC group. The primary end point was the number of patients with recurrent AP during the follow-up. All recurrent attacks of AP after an initial IAP episode were registered., Results: During a median follow-up of 36 (5-58) months, the recurrence of IAP was significantly higher in the control group than in LCC group (14/46 vs. 4/39, P = 0.016), as was also the number of recurrences (23/46 vs. 8/39, P = 0.003). In the subgroup of patients with at least 24 months' follow-up, the recurrence was still higher among controls (14/37 vs. 4/35, P = 0.008). In patients with normal liver function, recurrence was also significantly higher in the control than in the LCC group (13/46 vs. 4/39, P = 0.026). During surgery, 23/39 (59%) of the gallbladders were found to contain biliary stones or sludge., Conclusions: LCC can effectively prevent the recurrence of IAP when all other possible etiologies of pancreatitis are carefully excluded. A total of 5 patients needed to be treated (NNT-value) to prevent 1 IAP.