Blood Interleukin-18 (IL-18) and IL-18 Binding Protein (IL-18BP) Levels Following Midline Laparotomy: A Prospective Randomized Study of Patients With Benign Disease and Patients With Cancer.

BACKGROUND/AIM: The acute phase immune response (APR) in midline laparotomy (MLa) patients following surgery has been rarely studied, with no studies assessing the association of blood IL-18 (interleukin-18) and IL-18BP (IL-18 binding protein) values with the numeric rating scale (NRS) pain score following MLa. PATIENTS AND METHODS: Blood levels of seven cytokines (CYT) (IL-18, IL-18BP, IL-1ra, IL-6, IL-8, IL-10, IL-1ß) and high-sensitivity C-reactive protein (hs-CRP) were measured at three time points; before operation (PRE), immediately after operation (POP1), and 24 h after operation (POP2) in 56 patients with MLa. The satisfaction of the patients at 24 h following MLa (SFS24; 0=fully unsatisfied; 10=fully satisfied) was recorded on a 11-point numeric rating scale. RESULTS: In all patients, the IL-18 and IL-18BP blood levels decreased at POP1 and the drop between the preoperative and POP1 levels in the IL-18 and IL-18BP was highly significant (p<0.001). However, the median IL-18 and IL-18BP blood levels increased significantly at POP2 (p<0.001) with the linear mixed-effect model (LME) showing a statistically significant time effect (p<0.001). The hs-CRP blood levels increased significantly at POP2 with the LME model showing a statistically significant time effect. The preoperative and POP2 IL-18 values were clearly higher in patients with cancer versus benign disease (177/182 vs. 135/126, p=0.039/p=0.013, respectively). Interestingly, in all patients of the study, the median IL-18 versus IL-18BP blood levels correlated at POP1 (r=0.315, p=0.036). CONCLUSION: A noteworthy discovery of this study is the correlation of IL-18BP with SFS24 (r=0.361, p=0.05), proposing that APR and quality of life are associated in MLa patients.

Patient-reported Outcome Measure (PROM) Rand-36-item Health Survey for Gallstone Disease Patients Five Years Following Surgery: A Prospective Randomized Study.

BACKGROUND/AIM: There are no studies assessing the long-term quality of life (QoL) following three-dimensional laparoscopy cholecystectomy (3D-LC) in patients with cholelithiasis (Chole). PATIENTS AND METHODS: A cohort of 200 patients with Chole were randomized into 3D-LC or minilaparotomy cholecystectomy (MC) groups. RAND-36 survey was performed before randomization, four weeks and five years postoperatively. RESULTS: Similar postoperative five years RAND-36 scores were reported in the 3D-LC and MC groups. The MC and 3D-LC groups combined analysis, social functioning (SF, p=0.007), mental health (MH, p=0.001), role physical (RP, p<0.001) and bodily pain (BP, p<0.001) domains increased significantly. In comparison to the Finnish reference RAND-36 (FRR) scores, the scores at five years increased significantly in the MH domain, while four RAND-36 domains; Physical functioning (PF), general health (GH), RP, BP remained significantly lower in comparison to the FRR scores. CONCLUSION: A relatively similar long-term outcome in the 3D-LC and MC patients is shown. Interestingly, five RAND-36 domains increased during five years follow-up, while four RAND-36 domains remained lower than FRR scores, which may indicate onset of possible new symptoms following cholecystectomy in long-term follow-up.

Accuracy of Prediction Models in Diagnosis of Acute Diverticulitis.

BACKGROUND/AIM: The diagnostic score models (DMs) for patients with acute diverticulitis (AcDi) have been rarely evaluated. Therefore, we tried to develop diagnostic models (DMs) to enhance the diagnostic accuracy (DA) of AcDi. PATIENTS AND METHODS: In this AAP (acute abdominal pain) cohort, 30 AcDi patients were compared to 1,303 non-AcDi patients, with regard to their i) clinical symptoms (n=22), ii) signs and tests (n=14) as well as iii) laboratory analyses (n=3). The triage was performed at patient arrival to the emergency department (ED) (triage I) and at follow-up (triage II) before final decision. The triage included a suggested diagnosis of the AAP patient. Bivariate random effects meta-analysis was performed separately for 1) the pooled symptoms (n=22), 2) signs & tests (n=17) as well as 3) pooled DMs (I-V) with different cut-offs (with or without triage) to assess the diagnostic accuracy (DA) in detection of AcDi by HSROC (hierarchical summary receiver operating characteristic) curves. RESULTS: In the conventional receiver operating characteristic (ROC) analysis (for test optimization and finding optimal cut-off points), the area under curve (AUC) reached the following values for AcDi: i) DM without triage, AUC=0.843, ii) DM with triage I, AUC=0.866 and iii) DM with triage I and II, AUC=0.926. In the HSROC analysis, the AUC values for detection of AcDi were as follows; i) pooled clinical symptoms, AUC=0.540, ii) pooled clinical signs & tests, AUC=0.556 and iii) pooled DMs globally, AUC=0.853. In roccomp analysis for differences in AUC values: i) and iii) p<0.0001; between ii) and iii) p<0.0001. CONCLUSION: As confirmed by ROC and HSROC analysis, the new DMs with triage mode proved to be far superior in their DA for AcDi as compared to both symptoms and signs & tests. In the lack of earlier studies, these data report the first evidence that the DM including triage at an ED could improve the detection of AcDi.

A Possible Role of Interleukin-18 Binding Protein in Immune Regulation of Postoperative Pain: A Prospective Randomized Clinical Trial.

BACKGROUND/AIM: A possible role of interleukin-18 binding protein (IL-18BP) in immune regulation of pain and analgesics following surgery is rarely studied. The aim of this study was to investigate serum IL-18BP values in a cohort of laparoscopic cholecystectomy (LC) and minilaparotomy cholecystectomy (MC) patients and to establish their relationship with other cytokines and number of analgesic doses (NAD) of LC and MC patients postoperatively. PATIENTS AND METHODS: Blood levels of IL-18BP, six other interleukins (IL-18, IL-1ra, IL-6, IL-10, IL-1ß, and IL-8) and high-sensitivity C-reactive protein were measured before operation (PRE), immediately after operation (POP1), and six hours after operation (POP2) in 114 patients with cholelithiasis. RESULTS: Following surgery, the mean serum IL-18BP values correlated significantly to numeric rating scale (NRS) pain scores at 24 hours (r=0.194, p=0.009). In addition, the mean serum IL-18BP values correlated significantly to NAD (r=0.254, p<0.001). CONCLUSION: IL-18BP, a soluble antagonist of IL-18, correlates to NRS and NAD in LC and MC patients, which may support a possible role of IL-18BP in immune regulation of postoperative pain.

First RAND-36-Item Health Survey in Three-dimensional Laparoscopy Cholecystectomy: A Prospective Randomized Study.

BACKGROUND/AIM: National healthcare organizers require feedback from patients to improve medical treatment methods. Three-dimensional laparoscopy cholecystectomy (3D-LC) is a modern technique in surgery. However, there are no studies with patient feedback from validated questionnaires assessing the postoperative treatment results in 3D-LC. PATIENTS AND METHODS: Initially 200 patients with symptomatic cholelithiasis were randomized into 3D-LC or mini-laparotomy cholecystectomy (MC) groups. RAND-36-Item Health Survey was performed preoperatively and 4 weeks following surgery relating the survey scores between the 3D-LC and MC groups. RESULTS: Similar postoperative RAND-36 scores were reported for both groups preoperatively and at 4 weeks following surgery, and no significant differences in RAND-36 domains were shown. When the patients in both study groups were combined, Mental Health (p<0.001), Bodily Pain (p=0.01) and General Health (p=0.016) domain scores were significantly higher, indicating a significantly positive change in quality of life 4 weeks postoperatively, while those for the Role-Physical domain were significantly lower, indicating reduced physical activity during the 4 weeks following surgery. In comparison to the Finnish reference RAND-36 scores, scores at 4 weeks were significantly higher for the Mental Health domain (MC group, p<0.001 and 3D-LC group, p=0.001) whilst scores were significantly lower in four other domains: Physical Functioning, Social Functioning, Bodily Pain and Role-Physical. CONCLUSION: This study shows, for the first time using the RAND-36-Item Health Survey, relatively similar short-term outcomes in patients 4 weeks following cholecystectomy by 3D-LC and MC. Although scores for three RAND-36 domains were significantly higher postoperatively, indicating a significantly positive change in quality of life, a longer follow-up after cholecystectomy is needed for final conclusions to be drawn.

ACE inhibitors and the risk of acute pancreatitis-a population-based case-control study.

PURPOSE: The aim of this study was to examine the association between angiotensin converting enzyme (ACE) inhibitor use and the risk of acute pancreatitis. METHODS: Information on all 4966 cases hospitalized in 2008-2010 for acute pancreatitis was retrieved from the Finnish national registers on hospital discharges and prescriptions. A total of 24 788 age and sex-matched population-based controls were randomly selected using density sampling. ACE inhibitor use between 1 January 2003 and the index date were determined by the date of hospitalization for acute pancreatitis among the cases. The incidence rate ratios of acute pancreatitis not diagnosed as biliary or alcohol-induced were modeled by conditional logistic regression and adjusted for comorbidities. RESULTS: A total of 1276 (26%) cases and 3946 (16%) controls had been exposed to ACE inhibitors. The use of ACE inhibitors was associated with an increased incidence rate of acute pancreatitis (odds ratio [OR] 1.76, 95% confidence interval [CI] 1.59-1.95). The increase was slightly higher among current new users (OR 1.86, 95%CI 1.65-2.09) and somewhat lower among current prevalent (OR 1.54, 95%CI 1.35-1.75) and former users (OR 1.51, 95%CI 1.31-1.74). CONCLUSIONS: Angiotensin converting enzyme inhibitor use seems to be associated with a moderately increased risk of acute pancreatitis. Copyright © 2017 John Wiley & Sons, Ltd.

Can Laparoscopic Cholecystectomy Prevent Recurrent Idiopathic Acute Pancreatitis?: A Prospective Randomized Multicenter Trial.

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.

Use of statins and the risk of acute pancreatitis: a population-based case-control study.

PURPOSE: The aim of this research was to examine the association between statin use and the risk of acute pancreatitis. METHODS: This register-based case-control study with incidence density sampling was based on 4376 patients hospitalized in 2008-2010 for acute pancreatitis and 19 859 randomly selected age and sex-matched controls from the adult population of Finland. The relationship between statin use from 1 January 2004 to the index date and the relative incidence rate of acute pancreatitis was modelled by conditional logistic regression. The rate ratios were adjusted for comorbidities. RESULTS: A total of 826 (19%) cases and 2589 (13%) controls had been exposed to statins. Statin use was associated with an increased incidence rate of acute pancreatitis (odds ratio (OR) 1.25, 95% confidence interval (CI) 1.13-1.39). This increase was seen especially during the first year of use both among current (OR 1.37, 95% CI 0.94-2.00 for at most 3 months of use and OR 1.32, 95% CI 1.07-1.63 for 4-12 months of use) and former users (OR 1.64, 95% CI 1.33-2.03). The overall association remained when restricting analyses to participants with current use only, or with no history of gallstone or alcohol-related diseases, or with no comorbidities or medicines other than statins. CONCLUSIONS: Statin use seems to be associated with an increased risk of acute pancreatitis. The association is more apparent during the first year of statin use and among former users.

Effect of statin use on outcome of symptomatic cholelithiasis: a case-control study.

BACKGROUND: Statins can modify bile cholesterol and, thus, the formation of gallstones. We examined whether statin use also modifies the severity of symptomatic gallstone disease and its treatment. METHODS: A total of 1,140 consecutive patients with symptomatic gallstone disease were recruited during 2008-2010 at Kuopio university hospital, Finland. Case-control analysis matched the patients using (n = 272) or not using (n = 272) statins by age and sex. The baseline characteristics of the patients, need and type of surgical treatment, duration of operation, perioperative bleeding, postoperative complications and overall mortality rate were compared statistically between the study groups. RESULTS: Morbidity and subsequent polypharmacy occurred more frequently among the patients with statins compared to the patients without statins. There were no significant differences between the statin users and non-users regarding surgical treatment (open vs. laparoscopic cholecystectomy). The mean operation time for laparoscopic cholecystectomy was 10% shorter for the patients with statin use than for the patients without. In addition, there was a non-significant tendency for statin users to bleed less during laparoscopic operations than the non-users. There were no differences in other procedure-related parameters (e.g., operation urgency, conversions, choledochotomies, complications and mortality) in patients with or without statins. CONCLUSIONS: Compared to no treatment, statin treatment was associated with a shorter operation time for laparoscopy cholecystectomy. Other surgical outcome parameters were similar in patients with or without statins, although statin users had more polypharmacy and circulatory illnesses than non-users.

Statin use in patients with acute pancreatitis and symptomatic gallstone disease.

OBJECTIVE: The long-term use of statins may be associated with a decreased risk for gallstones and biliary-induced acute pancreatitis (AP). Our aim was to study the relationship of statin use and outcome of AP. METHODS: We investigated the records of 461 consecutive patients with AP and 1140 patients with symptomatic gallstones during 2008 to 2010. The use of lipid-lowering drugs, patient's characteristics, and outcome of patients were recorded. All known risk factors for AP and particularly statin use in idiopathic AP were analyzed. RESULTS: Statin use was comparable between the patients with AP (22%) and patients with cholelithiasis (24%). The frequencies of surgical treatment, duration of hospital stay, or mortality were not different between the statin users compared with the nonusers. Idiopathic AP was more often associated with the use of statins than alcohol- or gallstone-induced AP (44% vs 30% vs 13%, P < 0.002). The etiology of AP was alcohol in 56% of the patients, gallstones in 28% of the patients, and unknown (idiopathic) or miscellaneous in 16% of the patients. CONCLUSIONS: No beneficial effect of statins was observed in mortality or other outcome parameters of patients with AP. Statin use was more frequent in patients with idiopathic AP than in patients with biliary- or alcohol-induced AP.

Diagnostic score in acute appendicitis. Validation of a diagnostic score (Lintula score) for adults with suspected appendicitis.

PURPOSE: We have previously constructed and validated a diagnostic score to reduce the negative appendicectomy rate in children with suspected appendicitis. The purpose of this prospective study was to validate the diagnostic score (Lintula score) in adults with suspected appendicitis. METHODS: A total of 177 patients with suspected appendicitis were randomly assigned to either the appendicitis-score-group (n = 96) or the no-score-group (n = 81). The management decision was based on the use of the diagnostic scoring system in the appendicitis-score-group and on a sole clinical assessment in the no-score-group. The main diagnostic performance parameters were the diagnostic accuracy, specificity and sensitivity, the positive and negative predictive values, and the rate of negative appendicectomies. RESULTS: There was no difference between the appendicitis-score-group and the no-score-group in the diagnostic accuracy (92% vs. 91%; P = NS) and the negative appendicectomy rate (13% vs. 16%). Following repeated clinical examination, the diagnostic accuracy improved in both groups, 74% vs. 92% in the appendicitis-score-group (P = 0.01), and 84% vs. 91% in the no-score-group (P = 0.01). The application of the Lintula score yielded a higher positive predictive value (98% vs. 84%; P = 0.02) and specificity (98% vs. 84%; P = 0.028), but a lower negative predictive value (86% vs. 100%; P = 0.016) and sensitivity (87% vs. 100%; P = 0.022) than unaided clinical examination in the no-score-group. There were no differences in terms of the length of hospital stay, rate of complications and appendiceal histology between the two groups. CONCLUSION: The use of the acute appendicitis score developed for paediatric patients seems to provide some benefits compared to an unaided clinical diagnosis and may, thus, be a useful diagnostic tool for general surgeons.