P-suPAR may reflect the inflammatory response after pancreatic surgery.

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.

Osteoporosis and sarcopenia are common and insufficiently diagnosed among chronic pancreatitis patients.

PURPOSE: Chronic pancreatitis (CP) leads to diabetes and pancreatic exocrine insufficiency (PEI). PEI may lead to maldigestion and malnutrition, which may cause fat-soluble vitamin deficiency, sarcopenia and abnormal bone density. We aim to study the prevalence of osteoporosis, sarcopenia and vitamin deficiency among CP patients. METHODS: Long-term (4-5 years) follow-up was implemented on CP patients. We recorded CP duration, BMI, smoking, alcohol consumption and medication. We determined the serum values for A, D and E vitamins, albumin, creatinine, haemoglobin, calcium and magnesium. Bone density measurement was taken from the proximal femur and lumbar spine. CT/MRI scans were used to measure for psoas muscle area. RESULTS: A total of 33 patients (median age 62 [39-81] years, 61% male) were included. None of these patients had earlier diagnosis of osteopathy, and none of them had known vitamin deficiency or were sarcopenic. Nineteen patients (57%) had pancreatic exocrine insufficiency and of these seven patients (37%) had no pancreatic enzyme replacement therapy (PERT) and one (5%) had inadequate enzyme therapy. During the study, osteoporosis was diagnosed in 20% and possible sarcopenia in 48% of patients. PEI and inadequate PERT was associated with low E vitamin levels (75% vs. 0%, p = 0.012), higher risk of osteoporosis (43% vs. 5.6%, p = 0.013) and sarcopenia (80% vs. 36%, p = 0.044). CONCLUSION: This study demonstrates that chronic pancreatitis is associated with osteoporosis, sarcopenia and vitamin deficiency. If untreated, pancreatic exocrine insufficiency is associated with increased risk of these outcomes. This highlights the importance of identifying and treating PEI in CP patients.

Long-term (10-year) outcomes and prognostic factors in resected intraductal papillary mucinous neoplasm tumors in Finland: A nationwide retrospective study.

BACKGROUND: The degree of dysplasia is the most important prognostic factor for patients with resected intraductal papillary mucinous neoplasms. Intraductal papillary mucinous neoplasms are predominantly premalignant conditions; in most cases, surveillance is an adequate treatment. If worrisome features are present, surgery should be considered. However, there is limited data on the long-term prognosis of resected intraductal papillary mucinous neoplasms. We aimed to ascertain the nationwide survival of patients with resected intraductal papillary mucinous neoplasms and identify factors associated with survival. METHODS: This is a retrospective nationwide cohort study. All intraductal papillary mucinous neoplasms operated on in Finland between 2000 and 2008 were identified. Patient records were evaluated, and original radiologic data and histologic samples were re-evaluated. Survival data were collected after a 10-year follow-up period. RESULTS: Out of 2,024 pancreatic resections, 88 were performed for intraductal papillary mucinous neoplasm. The median age of the patients was 65 years. Histologic diagnoses were main duct intraductal papillary mucinous neoplasm 47/88 (53,4%), mixed-type intraductal papillary mucinous neoplasm 27/88 (30.7%), and branchduct intraductal papillary mucinous neoplasm 14/88 (15.9%). Of the tumors, 40/88 (45.5%) were low-grade dysplasia, 9/88 (10.2%) high-grade, and 39/88 (44.3%) were invasive cancer. The median survival was 121 (range 0-252) months. Ten-year survival was 72.5%, 66.7%, and 23.1% in the low-grade dysplasia, high-grade dysplasia, invasive cancer groups, respectively. Ten-year mortality for pancreatic cancer was 5%, 9.1%, and 71.8% in the low-grade dysplasia, high-grade dysplasia, invasive cancer groups, respectively. CONCLUSION: Overall, 44.3% of the patients had a malignant tumor, and three-quarters (74.5%) of the main duct intraductal papillary mucinous neoplasms were malignant or high-grade dysplasia at the time of surgery. Ten-year survival was significantly better in patients operated on at the stage of a premalignant tumor (low-grade dysplasia + high-grade dysplasia) than in patients operated on at the stage of a malignant tumor.

Plasma soluble urokinase-type plasminogen activator receptor (P-suPAR) in the diagnostics between malignant and non-malignant pancreatic lesions.

BACKGROUND: Soluble urokinase-type plasminogen activator receptor (suPAR) is a biomarker elevated in several inflammatory conditions and cancers. It has recently been shown to be elevated in pancreatic ductal adenocarcinoma (PDAC). Plasma suPAR (P-suPAR) predicts the severity of the disease in first acute alcohol-induced pancreatitis (AAP) and ten-year mortality after recovery from first AAP. According to our previous results, P-suPAR is not elevated in chronic pancreatitis (CP) and could possibly be used in distinguishing pancreatic cancer (PC) from CP. When imaging creates a suspicion of a pancreatic lesion, the distinction between malignant and non-malignant disease is crucial. Additional tools are needed, and we still lack a sufficiently sensitive and specific biomarker. Our aim was to further investigate whether preoperatively measured P-suPAR is beneficial in distinguishing between malignant and non-malignant pancreatic lesions. METHODS: One hundred and seventy-six patients evaluated in Tampere University Hospital for pancreatic surgery for suspected malignant pancreatic lesion were recruited for the study. The final study group consisted of 113 patients. P-suPAR and other covariates were measured before the planned operation. RESULTS: P-suPAR was significantly higher in patients with pancreatic cancer (PC) [median 4.1 (IQR 3.3-5.1) ng/mL] than in patients with non-malignant [3.3 (2.9-4.4) ng/mL; p = 0.012] histology. ROC curve analysis resulted in an AUC of 0.65 (95% CI 0.55-0.76); p = 0.007 and a cutoff value of 3.2 ng/mL. Crosstabulation yielded sensitivity of 82% and specificity of 43%. A combination of positive P-suPAR and elevated plasma carbohydrate antigen 19-9 (P-CA19-9) tests did not improve sensitivity but elevated specificity up to 86-88%. CONCLUSIONS: Preoperative P-suPAR is elevated in patients with PC compared to patients with a non-malignant pancreatic lesion. Combining P-suPAR with P-CA19-9 may improve diagnostic accuracy.

Pancreatic Secretory Trypsin Inhibitor (SPINK1) Gene Mutation in Patients with Acute Alcohol Pancreatitis (AAP) Compared to Healthy Controls and Heavy Alcohol Users without Pancreatitis.

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.

Smoking cessation intervention prior to orthopedic surgery: A study protocol to determine patient outcomes and feasibility.

The aim of the study is to analyze the effect of smoking and smoking cessation on the incidence of complications among orthopedic and hand surgery patients, and to determine the feasibility of smoking cessation intervention, as well as factors predicting success in smoking cessation. Orthopedic and hand surgery patients will be invited to participate in the study, which will recruit 550 participants (at least 20% daily smokers). A participant will be defined as a daily smoker if he/she reports daily smoking and/or laboratory tests show active smoking. Data will be collected using a self-reported questionnaire and from medical records. Smokers will receive information about the benefits of smoking cessation and will be encouraged to quit. Medication or nicotine replacement therapy will be prescribed. Laboratory tests will be taken two weeks before and two weeks after surgery. Follow-up phone calls will be made at 3, 6, and 12 months after surgery. The primary outcome is any complication, defined as a prolonged stay in hospital or any additional visit to or measure taken by a health service during the 12 months after surgery. Data on complications are mainly obtained from personal health records and from the information received at the follow-up; the rest of the data will be collected from the register of healthcare-associated infections. Secondary outcomes are the number and types of complications. The sample (n=550) was calculated to observe a 10% difference in complications between smokers and non-smokers (5% alpha level and 80% power), considering a 10% drop-out rate. Logistic regression and log-linear models will be used for data analyses.

The association between appendicitis severity and patient age with appendiceal neoplasm histology-a population-based study.

PURPOSE: Recent studies have reported alarming appendiceal tumor rates associated with complicated acute appendicitis, especially in patients presenting with a periappendicular abscess. However, the data on histology of appendiceal tumors among acute appendicitis patients is limited, especially in patient cohorts differentiating between uncomplicated and complicated acute appendicitis. We have previously reported the association of increased appendiceal tumor prevalence with complicated acute appendicitis in this population-based study. The objective of this secondary analysis was to evaluate the association of both appendicitis severity and patient age with appendiceal tumor histology. METHODS: This nationwide population-based registry study (The Finnish Cancer Registry) was conducted from 2007 to 2013. All appendiceal tumors (n = 840) and available medical reports (n = 504) of these patients at eight study hospitals were previously evaluated, identifying altogether 250 patients with both acute appendicitis and appendiceal tumor. RESULTS: The severity of acute appendicitis was significantly associated with more malignant tumor histology. The risk of adenocarcinoma or pseudomyxoma was significantly higher among patients with periappendicular abscess (OR 15.05, CI 95% 6.98-32.49, p < 0.001) and patients presenting with perforated acute appendicitis (OR 4.09, CI 95% 1.69-9.90, p = 0.0018) compared to patients with uncomplicated acute appendicitis. Similarly, patient age over 40 years was significantly associated with the risk of adenocarcinoma and pseudomyxoma (OR 26.46, Cl 95% 7.95-88.09, p < 0.001). Patient sex was not associated with a more malignant appendiceal tumor histology (p = 0.67). CONCLUSION: More malignant appendiceal tumor histology of adenocarcinoma or pseudomyxoma was significantly associated with patient age over 40 years and complicated acute appendicitis, especially periappendicular abscess.

Long-term morbidity and mortality in patients diagnosed with an insulinoma.

OBJECTIVE: Insulinomas are rare functional pancreatic neuroendocrine tumours. As previous data on the long-term prognosis of insulinoma patients are scarce, we studied the morbidity and mortality in the Finnish insulinoma cohort. DESIGN: Retrospective cohort study. METHODS: Incidence of endocrine, cardiovascular, gastrointestinal and psychiatric disorders, and cancers was compared in all the patients diagnosed with an insulinoma in Finland during 1980-2010 (n = 79, including two patients with multiple endocrine neoplasia type 1 syndrome), vs 316 matched controls, using the Mantel-Haenszel method. Overall survival was analysed with Kaplan-Meier and Cox regression analyses. RESULTS: The median length of follow-up was 10.7 years for the patients and 12.2 years for the controls. The long-term incidence of atrial fibrillation (rate ratio (RR): 2.07 (95% CI: 1.02-4.22)), intestinal obstruction (18.65 (2.09-166.86)), and possibly breast (4.46 (1.29-15.39) and kidney cancers (RR not applicable) was increased among insulinoma patients vs controls, P < 0.05 for all comparisons. Endocrine disorders and pancreatic diseases were more frequent in the patients during the first year after insulinoma diagnosis, but not later on. The survival of patients with a non-metastatic insulinoma (n = 70) was similar to that of controls, but for patients with distant metastases (n = 9), the survival was significantly impaired (median 3.4 years). CONCLUSIONS: The long-term prognosis of patients with a non-metastatic insulinoma is similar to the general population, except for an increased incidence of atrial fibrillation, intestinal obstruction, and possibly breast and kidney cancers. These results need to be confirmed in future studies. Metastatic insulinomas entail a markedly decreased survival.

Perioperative acinar cell count method works well in the prediction of postoperative pancreatic fistula and other postoperative complications after pancreaticoduodenectomy.

BACKGROUND: Earlier we have shown that high frequency of acinar cells in the pancreatic transsection line predicts postoperative pancreatic fistula after pancreaticoduodenectomy (PD). Acinar cell count method (ACM) is fast to perform during operation. In this study our aim was to validate the accuracy of ACM to compare it with other published risk prediction methods. METHODS: 87 patients who underwent PD without any trial including perioperative medications were collected from a single hospital. Data on demographics, surgical details, postoperative complications clinically relevant pancreatic fistulae (CR-POPF) and clinically relevant Clavien-Dindo complications (CR-CDC) were registered. Thirteen previously published risk prediction methods were included in the comparison, such as pancreatic duct diameter, palpable texture of pancreas, Braga score (BC), Fistula Risk Score, Modified Fistula Risk Score, Alternative Fistula Risk Score and multiple radiological parameters. ROC-curves were calculated to compare sensitivity and specificity for identifying high risk patients for CR-POPF and CR-CDC. RESULTS: The three most accurate risk prediction methods for CR-POPF were ACM (sensitivity 88.9%, specificity 52.6%; p = 0.043), BC (87.5%, 56.6%; p = 0.039) and visceral fat area to subcutaneous fat area ratio (75.5%, 80.0%; p = 0.032). In predicting CR-CDC the three most accurate methods were ACM (73.9%, 56.2%; p = 0.033), BC (68.4%, 59.5%; p = 0.036) and TPAI (78.3%, 41.7%; p = 0.012). CONCLUSION: ACM was shown to be as good as the more complicated risk scoring methods in the prediction of CR-POPF. It was good also in predicting all clinically relevant complications. ACM is easy to use during operation and can be recommended as a routine risk prediction method.

Regulation of p38 MAPK and glucocorticoid receptor activation by hydrocortisone in mono-and co-cultured pancreatic acinar and stellate cells.

BACKGROUND/OBJECTIVES: Acute pancreatitis develops as an inflammatory response to pancreatic tissue injury. Postoperative pancreatitis has recently been associated with increased occurrence of complications. Activation of the mitogen-activated protein kinase p38 (p38 MAPK) pathway occurs early in acute pancreatitis and its inhibition has been suggested to alleviate pancreatic inflammation. Glucocorticoids are potent anti-inflammatory steroids whose use in the management of acute pancreatitis remains controversial. Our aim was to examine the effect of crosstalk between pancreatic acinar cells (PACs) and stellate cells (PSCs) on p38 MAPK and glucocorticoid receptor (GR) activation and to assess the impact of hydrocortisone on these events. METHODS: The long-term co-culture setting for mouse PACs and PSCs developed in our laboratory was used. Parallel 4d mono- and co-cultures with or without 10 nM hydrocortisone were performed followed by immunocytochemical analysis of nuclear GR and phospho-p38 MAPK (pp38 MAPK). RESULTS: Hydrocortisone inhibited pp38 MAPK up-regulation evoked by co-culture in PACs and PSCs and increased nuclear translocation of GR in PAC monocultures and in co-cultured PACs and PSCs. In PSC monocultures and co-cultured PACs, ligand-independent expression of nuclear GR was observed. In the former no change in nuclear GR but a significant decrease in total GR as analyzed by Western blot was caused by hydrocortisone. CONCLUSIONS: Cellular microenvironment plays a significant role on p38 MAPK and GR activation in PACs and PSCs. Hydrocortisone is an effective means to inhibit p38 MAPK activation in PACs and PSCs. Both ligand-dependent and -independent regulatory roles for GR are suggested in the exocrine pancreas.

Surgery for chronic pancreatitis in Finland is rare but seems to produce good long-term results.

BACKGROUND: Abdominal pain in chronic pancreatitis (CP) may require invasive interventions. Surgical procedures are rare, and little is known about the long-term results. AIM: To study the nationwide frequency of pancreatic surgery for CP in Finland, and postoperative symptoms and quality of life (QoL). METHODS: All patients in Finland with a diagnosis of CP who had undergone pancreatic surgery during 2000-2008 were selected from a national register. Only patients with CP as an indication for pancreatic surgery were included. Medical records were studied and questionnaires QLQ-C30, PAN26 and AUDIT, and symptom questionnaires were sent out. RESULTS: During the 9-year period, pancreatic surgery for CP was performed on 30 patients [77% men, median age 45 (21-62) years]. Eighty-three percent underwent endoscopic procedures before surgery. Surgery was performed a median 2 (0-10) years after the original CP diagnosis, and 17% developed postoperative complications. Primary pain relief after surgery was reported in 70% of cases. Need for strong pain medication was lower after surgery. Eight of 21 (38%) returned the questionnaires and 88% reported that surgery had reduced their pain and 63% were almost or entirely pain-free at a median 14 (10-18) years after surgery. QoL results did not differ from those in our control Finnish CP group. CONCLUSION: Surgery for CP is rare in Finland and most patients had prior endoscopic procedures. Patients who returned the questionnaires reported less pain and good QoL during the 14-year follow-up.

Long-term health-related quality of life in persons diagnosed with an insulinoma in Finland 1980-2010.

OBJECTIVE: Insulinomas are rare pancreatic neoplasms, which can usually be cured by surgery. As the diagnostic delay is often long and the prolonged hyperinsulinemia may have long-term effects on health and the quality of life, we studied the long-term health-related quality of life (HRQoL) in insulinoma patients. DESIGN, PATIENTS AND MEASUREMENTS: The HRQoL of adults diagnosed with an insulinoma in Finland in 1980-2010 was studied with the 15D instrument, and the results were compared to those of an age- and gender-matched sample of the general population. The minimum clinically important difference in the total 15D score has been defined as ±0.015. The clinical characteristics, details of insulinoma diagnosis and treatment, and the current health status of the subjects were examined to specify the possible determinants of long-term HRQoL. RESULTS: Thirty-eight insulinoma patients participated in the HRQoL survey (response rate 75%). All had undergone surgery with a curative aim, a median of 13 (min 7, max 34) years before the survey. The insulinoma patients had a clinically importantly and statistically significantly better mean 15D score compared with the controls (0.930 ± 0.072 vs 0.903 ± 0.039, P = .046) and were significantly better off regarding mobility, usual activities and eating. Among the insulinoma patients, younger age at the time of survey, higher level of education and smaller number of chronic diseases were associated with better overall HRQoL. CONCLUSIONS: In the long term, the overall HRQoL of insulinoma patients is slightly better than that of the general population.

Plasma suPAR may help to distinguish between chronic pancreatitis and pancreatic cancer.

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.

The European evidence-based guidelines on pancreatic cystic neoplasms (PCN) in clinical practice: The development of relative and absolute indications for surgery during prospective IPMN surveillance.

INTRODUCTION: The European evidence-based guidelines on PCN recommend surveillance for IPMN patients who are fit for surgery but who have no indication for immediate surgery. Our aim was to demonstrate the feasibility of the new guidelines in clinical practice. METHODS: This is a prospective cohort study of patients included in the IPMN register in Tampere University Hospital, Finland. IPMN was diagnosed from January 1, 2013 to December 31, 2018. Patients were analyzed for surveillance and indications for surgery according to the European guidelines on PCN. RESULTS: Out of 128 patients in register 23 was decided to operate upfront and 105 patients were included in the surveillance programme. Invasive carcinoma was found in 4/23 of operated patients. Median follow-up time was 26 months (6-69). Median size of the cyst at the beginning and end of the surveillance was 16 mm (4-58 mm). During surveillance 0/105 (0.0%) patients had or developed an absolute indication for surgery. Relative indication for surgery was present in 8/105 (7.6%) patients in the beginning surveillance and 9/105 (8.6%) patients developed at least one relative indication for surgery during surveillance. From the surveillance cohort 2/105 patients were operated. Surveillance was abandoned in 15/105 (14.1%) patients all due to poor general condition or other medical conditions. CONCLUSIONS: In clinical practice, surveillance of IPMN according to the European guidelines on PCN is feasible. Among our patients 16% were detected to have relative indications for surgery during the median 26 (range 3-135) months of surveillance. Nearly 15% became surgically unfit during surveillance period.

A population-based study of chronic pancreatitis in Finland: Effects on quality of life.

BACKGROUND/OBJECTIVES: In Finland the incidence of chronic pancreatitis (CP) is high compared to that in most European countries. Recent epidemiological data is lacking. Our aim was to investigate the current epidemiologic and behavioural data on CP patients in Finland. METHODS: CP patients according to M-ANNHEIM criteria in Tampere University Hospital (TAUH) during 2014-2015 were included. Aetiology, time from diagnosis, pancreatic function, treatment, complications, smoking, alcohol consumption (AUDIT) and quality of life (QoL) (QLQ C30, PAN26) were gathered. RESULTS: 235 CP patients (57 (26-88) years, 65% men) were included. Time since diagnosis was 5.5 (1-41) years. Aetiology was alcohol in 67%, and smoking contributed in 54%. Of these patients 78% continued smoking and 58% continued to consume alcohol even after CP diagnosis. CP related complications were common. Pseudocysts were more common in alcohol related CP than in non-alcohol related CP (60% vs. 38%, p < 0.05). Reported QoL and pain were worse in the CP patients than in controls. Alcohol consumption differed from that of the Finnish population; the CP patients were either total abstainers or heavy alcohol consumers. CONCLUSIONS: CP constitutes a great burden on the health care system and on the patients. The patients frequently develop complications and symptoms and their QoL is inferior to that of controls. The most important measure to halt the progression of CP would be to prevent acute phases and for patients to stop smoking, which does not happen in many CP patients. It would be beneficial to increase awareness among CP patients and medical professionals.

Quality of Life and Patient Satisfaction at 7-Year Follow-up of Antibiotic Therapy vs Appendectomy for Uncomplicated Acute Appendicitis: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Long-term results support antibiotics for uncomplicated acute appendicitis as an alternative to appendectomy. To our knowledge, treatment-related long-term patient satisfaction and quality of life (QOL) are not known. Objective: To determine patient satisfaction and QOL after antibiotic therapy and appendectomy for treating uncomplicated acute appendicitis. Interventions: Open appendectomy vs antibiotics with intravenous ertapenem, 1 g once daily, for 3 days followed by 7 days of oral levofloxacin, 500 mg once daily, and metronidazole, 500 mg 3 times per day. Design, Setting, and Participants: This observational follow-up of the Appendicitis Acuta (APPAC) multicenter randomized clinical trial comparing appendectomy with antibiotics included 530 patients age 18 to 60 years with computed tomography-confirmed uncomplicated acute appendicitis who were randomized to undergo appendectomy (273 [52%]) or receive antibiotics (257 [49%]). The trial was conducted from November 2009 to June 2012; the last follow-up was May 9, 2018. The data were analyzed in February 2019. Main Outcomes and Measures: In this analysis, post hoc secondary end points of postintervention QOL (EQ-5D-5L) and patient satisfaction and treatment preference were evaluated. Results: Of the 530 patients enrolled in the trial (appendectomy group: 273 [174 men (64%)] with a median age of 35 years; (antibiotic group: 257 [155 men (60%)] with a median age of 33 years), 423 patients (80%) were available for phone interview at a median follow-up of 7 years; 206 patients (80%) took antibiotics and 217 (79%) underwent appendectomy. Of the 206 patients taking antibiotics, 81 (39%) had undergone appendectomy. The QOL between appendectomy and antibiotic group patients was similar (median health index value, 1.0 in both groups; 95% CI, 0.86-1.0; P = .96). Patients who underwent appendectomy were more satisfied in the treatment than patients taking antibiotics (68% very satisfied, 21% satisfied, 6% indifferent, 4% unsatisfied, and 1% very unsatisfied in the appendectomy group and 53% very satisfied, 21% satisfied, 13% indifferent, 7% unsatisfied, and 6% very unsatisfied in the antibiotic group; P < .001) and in a subgroup analysis this difference was based on the antibiotic group patients undergoing appendectomy. There was no difference in patient satisfaction after successful antibiotic treatment compared with appendectomy (cumulative odds ratio [COR], 7.8; 95% CI, 0.5-1.3; P < .36). Patients with appendectomy or with successful antibiotic therapy were more satisfied than antibiotic group patients who later underwent appendectomy (COR, 7.7; 95% CI, 4.6-12.9; P < .001; COR, 9.7; 95% CI, 5.4-15.3; P < .001, respectively). Of the 81 patients taking antibiotics who underwent appendectomy, 27 (33%) would again choose antibiotics as their primary treatment. Conclusions and Relevance: In this analysis, long-term QOL was similar after appendectomy and antibiotic therapy for the treatment of uncomplicated acute appendicitis. Patients taking antibiotics who later underwent appendectomy were less satisfied than patients with successful antibiotics or appendectomy. Trial Registration: Clinicaltrials.gov Identifier: NCT01022567.

Perioperative hydrocortisone treatment reduces postoperative pancreatic fistula rate after open distal pancreatectomy. A randomized placebo-controlled trial.

BACKGROUND: Postoperative pancreatic fistula (POPF) is the most common complication after distal pancreatectomy (DP). In a recent RCT on pancreaticoduodenectomy (PD), perioperative hydrocortisone (HC) treatment reduced Clavien-Dindo (C-D) III-V complications. The aim of this study was to investigate whether perioperative HC treatment reduces the overall complications and clinically significant POPF after distal pancreatectomy (DP). METHODS: Fourty consecutive patients undergoing DP were randomized to receive intravenous HC 100mg/placebo every eight hours until the second postoperative day. Thirty-one patients were completed with DP and received HC/placebo every 8 h for two days postoperatively. The primary endpoint was overall complications (C-D III-V) and the secondary endpoint was the development of clinically significant POPF. RESULTS: Pancreatic duct diameter, operative time and blood loss were similar in the groups. Ninety-day mortality was zero. With HC treatment the rates of C-D III-V complications tended to be lower compared to the placebo group (5.9% vs 21.4%, p = 0.034). The rate of grade B/C POPF was significantly reduced with HC treatment compared to the placebo group (5.9% vs. 42.9%, p = 0.028). CONCLUSION: Perioperative HC treatment may have a favourable effect on overall major complications after open DP. HC treatment reduces the incidence of clinically significant POPF after open DP.

Plasma level of soluble urokinase plasminogen activator receptor (suPAR) predicts long-term mortality after first acute alcohol-induced pancreatitis.

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.

Characteristics and long-term survival of resected pancreatic cystic neoplasms in Finland. The first nationwide retrospective cohort analysis.

BACKGROUND: Pancreatic cystic neoplasms (PCN) are being found increasingly in imaging studies. Even though the characteristics of PCN lesions have been studied extensively in single and multicentre settings, nationwide data is lacking. The aim of this study was to determine the nationwide epidemiologic characteristics and long-term survival of all resected PCNs. METHODS: For this retrospective cohort analysis, all PCNs operated on in Finland during the period 2000-2008 were identified. Data was collected from all patients: on demographics, comorbidities, symptoms, radiological findings, surgical procedures, complications, histopathological diagnoses and survival. Incomplete pathology reports and any uncertain diagnoses were re-assessed. Survival data was collected after a five-year follow-up period. RESULTS: The final database included 225 patients with operated PCN. After reviewing the incomplete pathology reports, in 44 cases the original diagnosis was changed, mostly from MCN to IPMN. The most common histopathological diagnoses were IPMN (94/225; 50/225 MD-IPMN, 30/225 MX-IPMN and 14/225 BD-IPMN), SCN (41/225) and MCN (40/225). Overall, 53/225 (23.6%) of the tumours were malignant. Malignancy was detected in MD-IPMN 29/50 (58%), MX-IPMN 10/30 (33.3%), MCN 12/40 (30%), BD-IPMN 2/14 (14.3%) patients. Median 5-year survival for all patients was 77%: 87% in patients without malignancy, 77% with HGD and 27% in patients with a malignant resected PCN. CONCLUSION: One fourth of the PCNs operated on nationwide were malignant, with a five-year survival of 27%, compared to overall survival of 87% in patients with non-malignant disease and 77% in those with HGD. Detecting - and operating on - a PCN before the malignant transfer remains a great challenge.

Wnt/ß-catenin signalling plays diverse functions during the process of fibrotic remodelling in the exocrine pancreas.

BACKGROUND/OBJECTIVES: Wnt/ß-catenin signalling plays vital roles in tissue homeostasis. Dysregulation of the pathway has been implicated in the pathogenesis of cancer and fibroses in numerous tissues, including the pancreas. We studied the effect of microenvironmental changes pertaining to fibrotic tissue remodelling on the expression of selected Wnt/ß-catenin pathway proteins in the human exocrine pancreas. The role of acinar/stellate cross-talk on the expression of the proteins was elucidated in a long-term mouse co-culture system. METHODS: Expression of ß-catenin, Wnt2, Wnt5a and SFRP4 was analysed immunohistochemically in normal and moderately or highly fibrotic human pancreata (n = 8). The effect of humoral interactions on the expression of the proteins was studied by immunocytochemical means in parallel mono- and co-cultures of mouse acinar and stellate cells (PSCs). RESULTS: In human pancreatic tissue, fibrotic microenvironment was associated with redistribution of the proteins in and between epithelial and stromal compartments, compared to acinar-rich tissue. In non-fibrotic and moderately fibrotic tissue the proteins appeared only in acinar cells whereas in highly fibrotic tissue stromal fibroblastoid/stellate cells and macrophages were their predominant locations. Subcellular changes in the expression of ß-catenin and Wnt5a were detected. Our in vitro data suggest potential involvement of acinar cell/PSC cross-talk in mediating the changes observed in tissue specimens. CONCLUSIONS: Wnt/ß-catenin pathway-associated proteins are abundantly expressed in the exocrine pancreas with prominent changes in their cellular and subcellular expression patterns along with increasing levels of fibrosis. Diverse functions for Wnt/ß-catenin signalling during the course of fibrotic remodelling in the exocrine pancreas are suggested.