Serum leptin and ghrelin levels in patients in the early stages of acute biliary pancreatitis and different degrees of severity.

UNLABELLED: Acute pancreatitis (AP) is a potentially fatal disease. In animal experiments leptin and ghrelin were shown to modulate the course of AP. The aim of the study was to estimate the relationship between the severity of acute biliary pancreatitis (ABP) and serum levels of leptin and ghrelin in nonobese patients in the first seven days of the hospitalization. MATERIAL AND METHODS: The study included nine patients with mild ABP (MABP), eleven patients with severe ABP (SABP) and twenty healthy controls, appropriately matched age, sex and weight. Serum concentrations of leptin and ghrelin were measured in patients on the first, third, fifth, and seventh days of hospitalization using leptin and ghrelin RadioImmunoAssay (RIA) kits. RESULTS: At admission and throughout the study the mean serum leptin concentration in SABP patients was higher than in the controls but without statistical significance. Serum ghrelin concentrations on admission were significantly lower in patients with ABP than in the controls. We observed steadily increasing serum ghrelin levels in both groups of the patients during the course of ABP. CONCLUSIONS: The results of our study do not support the role of leptin as a marker of the severity of ABP. On the other hand, rising serum ghrelin levels during the course of ABP may be a marker of recovery and an indicator of the healing process.

Plasma pentraxin 3 concentrations in patients with acute pancreatitis.

BACKGROUND: Pentraxin 3 (PTX3) belongs to the acute phase proteins; its concentration increases significantly in the early stages of inflammation. In nearly 20% of patients with acute pancreatitis (AP) escalated inflammation leads to the development of severe forms of the disease. The aim of this study was to evaluate the pattern of changes in PTX3 concentration in patients with AP at the early stage of the disease (first 5 days from admission) and to assess the relationship between PTX3 and other inflammatory markers. METHODS: The study included 40 patients with AP (16 women and 24 men)--12 with severe and 28 with mild form of AP. Concentrations of PTX3, serum amyloid A (SAA), C-reactive protein (CRP), hepatocyte growth factor (HGF), procalcitonin (PCT), polymorphonuclear elastase (PMN-elastase), interleukin 6 (IL-6), interleukin 18 (IL-18), and soluble receptor for TNFalpha (sTNFR75) were measured in samples collected on the 1st, 3rd, and 5th day of the hospital stay. Plasma PTX3 was measured also in the control group, consisting of 37 age and sex-matched healthy subjects. RESULTS: The highest concentrations of PTX3 were noted on the first day after admission. The concentrations were higher in patients with the severe compared to those with the mild form of AP (median 17.2 vs. 4.0 ng/mL on day 1, p = 0.03; 6.1 vs. 2.2 on day 5, p = 0.044). On each of the study days significant correlations were found between PTX3 and SAA, IL-6, and PMN-elastase (p < 0.05). CONCLUSIONS: The pattern of changes in PTX3 concentration in the early phase of AP is similar to that of IL-6, and its peak levels are achieved earlier compared to CRP. Our findings suggest that PTX3 may be useful in early evaluation and prediction of the severity of AP.

[Analysis of selected inflammatory markers for early prediction of severe clinical course of acute pancreatitis]. / Znaczenie wybranych markerów zapalnych dla wczesnego przewidywania ciezkosci przebiegu ostrego zapalenia trzustki.

Despite new diagnostic methods, including novel laboratory parameters and imaging techniques, and growing knowledge on pathogenesis of acute pancreatitis, early assessment of severity remains the main factor influencing prognosis in the disease. The aim of the study was the evaluation of diagnostic accuracy of interleukins (IL): 6 and 18 and acute phase proteins: C-reactive protein (CRP) and serum amyloid A (SAA), together with Glasgow prognostic score during first 48 hours after diagnosing acute pancreatitis in a group of 40 patients treated in the I-st Department of General and Gastrointestinal Surgery University Hospital in Cracow. All the studied inflammatory markers were significantly higher in patients with moderate and severe acute pancreatitis versus patients with mild form of the disease on the first 48 hours of the disease. Expanding Glasgow score with IL-6, IL-18, SAA or CRP determinations resulted in better accuracy for diagnosing severe clinical course of acute pancreatitis.

Individual patient data meta-analysis of organ failure in acute pancreatitis: protocol of the PANCREA II study.

CONTEXT: Organ failure is a major determinant of mortality in patients with acute pancreatitis. These patients usually require admission to high dependency or intensive care units and consume considerable health care resources. Given a low incidence rate of organ failure and a lack of large non-interventional studies in the field of acute pancreatitis, the characteristics of organ failure that influence outcomes of patients with acute pancreatitis remain largely unknown. Therefore, the Pancreatitis Across Nations Clinical Research and Education Alliance (PANCREA) aims to conduct a meta-analysis of individual patient data from prospective non-interventional studies to determine the influence of timing, duration, sequence, and combination of different organ failures on mortality in patients with acute pancreatitis. METHODS: Pancreatologists currently active with acute pancreatitis clinical research will be invited to contribute. To be eligible for inclusion patients will have to meet the criteria of acute pancreatitis, develop at least one organ failure during the first week of hospitalization, and not be enrolled into an intervention study. Raw data will then be collated and checked. Individual patient data analysis based on a logistic regression model with adjustment for confounding variables will be done. For all analyses, corresponding 95% confidence intervals and P values will be reported. CONCLUSION: This collaborative individual patient data meta-analysis will answer important clinical questions regarding patients with acute pancreatitis that develop organ failure. Information derived from this study will be used to optimize routine clinical management and improve care strategies. It can also help validate outcome definitions, allow comparability of results and form a more accurate basis for patient allocation in further clinical studies.

Serum proinflammatory cytokine levels and white blood cell differential count in patients with different degrees of severity of acute alcoholic pancreatitis.

UNLABELLED: Several studies suggest that cytokines and neutrophils play an important role in the pathogenesis of acute pancreatitis (AP). The AIM OF THE STUDY was to assess the systemic release of proinflammatory cytokines and WBC (white blood cells) count with differential in patients with acute alcoholic pancreatitis (AAP) and to characterize the differences between patients with mild and severe forms of the disease. MATERIAL AND METHODS: Thirty-five patients with the mild form of acute alcoholic pancreatitis (MAAP) were compared to 11 patients with severe acute alcoholic pancreatitis (SAAP). Serum levels of IL-6, IL-8, IL-12p40 and WBC differential count were measured every second day during the first week after admission. RESULTS: During the course of the study, the average level of IL-6 was significantly (p<0.05) higher in patients with SAAP than in patients with the mild form of the disease (MAAP). Serum levels of IL-8 and IL-12p40 on admission were higher in patients with SAAP than in patients with MAAP but the difference was not statistically significant. Of all the types of WBCs, neutrophils were significantly (p<0.05) elevated the entire time in SAAP patients when compared to patients with MAAP on 5th and 7th day from admission to hospital. CONCLUSIONS: Patients with SAAP had significantly higher proinflammatory cytokine IL-6 levels and neutrophil counts than patients with MAAP. The results suggest that proliferation and overstimulation of this subset of leukocytes might contribute to the development of the systemic inflammatory response in patients with SAAP.

[Analysis of osteopontin in patients with acute pancreatitis]. / Badanie osteopontyny u chorych z ostrym zapaleniem trzustki.

The aim of this study was to analyze osteopontin (OPN) concentrations in patients with acute pancreatitis (AP) and its suitability for diagnosis and prediction of severity during the first 3 days from admission to hospital. The study group consisted of 40 patients admitted and hospitalized at I-st and II-nd Depatments of Surgery Jagiellonian University Collegium Medicum in Krakow. All laboratory tests necessary for diagnosis and monitoring of patients were performed in the Diagnostic Dept. of University Hospital, other immunochemistry parameters were assesed in the Diagnostic Dept. of Clinical Biochemistry Jagiellonian University using ELISA kits. The concentrations of OPN in severe acute pancreatitis were significantly higher than in patients with mild form of disease in the whole observation period. Simultaneously, we observed that increased in OPN concentrations in consecutive days of AP may be helpful in prediction of severity and compilations during AP.

Serum matrix Gla protein concentrations in patients with mild and severe acute pancreatitis.

BACKGROUND: Acute pancreatitis (AP) causes an increase in proinflammatory cytokine and acute phase protein levels. Our previous studies in AP showed the role of fetuin A as a negative acute phase protein. Matrix Gla protein (MGP), beside fetuin A, is one of the main inhibitors of extraosseous calcification. In the present preliminary study we evaluated the relationship between MGP, lipase, and inflammation in AP patients. METHODS: The study included 40 patients with AP of diverse severity (28 mild, 12 severe), assessed during the early phase of AP (day 1 - day 7 of hospitalization). The concentration of MGP, fetuin A, polymorphonuclear elastase (PMN-elastase), interleukin 6 (IL-6), interleukin 18 (IL-18), hepatocyte growth factor (HGF), high sensitivity tumor necrosis factor alpha (hs TNFalpha), soluble receptor of tumor necrosis factor II (sTNFRII), and neopterin were measured by ELISA kits; albumin, lipase and amylase were measured on a Modular P Chemistry Analyser (Roche Diagnostica, Germany); procalcitonin (PCT) was measured using the LUMItest PCT (Brahms, Germany), and serum amyloid A (SAA) and high sensitivity C-reactive protein (hs CRP) were measured using an immunonephelometric method on a Nephelometer BNII (Siemens Healthcare, Germany). RESULTS: MGP positively correlated with lipase activity (R = 0.64; p < 0.05) on day 1 after admission to hospital. Lower MGP levels were consistent with higher intensity of inflammation, as MGP significantly (p < 0.05) inversely correlated with IL-6 (R = -0.48 on day 3; R = -0.46 on day 5 and R = -0.52 on day 7 after admission), IL-18 (R = - 0.55; R = -0.60; R = -0.48 on day 1, day 3, and day 5, respectively), HGF (R = -0.58 on day 3), hs TNFalpha (R = -0.45 on day 1 and R = -0.64 on day 5), its soluble receptor sTNFRII (R = -0.63; R = -0.61; R = -0.59 on day 3, day 5, and day 7, respectively), hs CRP (R = -0.76 on day 1 and R = -0.83 on day 5), PCT (R = -0.62 on day 1 and R = -0.59 on day 7), SAA (R = -0.45 on day 5) as well as with neopterin (R = -0.52 on day 1 after admission). MGP levels dropped simultaneously with fetuin A (R = 0.50 on day 3; R = 0.60 on day 5 and R = 0.63 on day 7) and albumin concentrations (R = 0.51; R = 0.70; R = 0.94 on day 1, day 5, and day 7 day after admission, respectively). There was a relationship between lipase activity and MGP concentration on day 1 of hospitalization (R = 0.64; p < 0.05). CONCLUSIONS: Our preliminary results indicate that the MGP level correlated negatively with all of the proinflammatory cytokines and acute phase proteins studied in patients with AP, and positively with lipase, fetuin A, and albumin measurements. These findings may indicate the role of MGP in calcium and phosphate metabolism disturbances in the course of AP.

Serum fetuin A concentrations in patients with acute pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is a mild and self-limiting disease in most patients, but necrotizing pancreatitis develops in up to 20 - 30% of the cases. Early recognition of severe AP has been considered as a key determinant of successful therapy. The aim of this study was to evaluate the clinical value of fetuin A as the new predictor of complications and fatal outcome during acute pancreatitis (AP). METHODS: The study included 40 patients with AP of diverse severity (28 mild, 12 severe), assessed during the early phase of AP (1st - 7th day of hospitalization). Fetuin A level was measured by ELISA kit (BioVendor). RESULTS: Median serum fetuin A concentrations had a tendency to decrease during examination from 0,371 g/L at admission to 0,288 g/L on the 7th day of hospitalization. In each of 7 days of observation, correlation between the increase in fetuin A and the absolute number of RBC was found (R = 0,34: 1st day R = 0,35: 3rd day, p < 0,05; R = 0,57: 5th day, p < 0,001; R = 0,65: 7th day, p < 0,01). Additionally, we observed the reverse relationship between the decrease in fetuin A and the increase in some inflammatory markers (IL-6: R = -0,61, p < 0,0001; SAA: R = -0,58, p < 0,001; HGF: R = -0,60, p < 0,01; PCT: R = -0,475, p < 0,01). The strongest positive correlation was noticed on the 5th day of hospitalization between decreased levels of fetuin A and albumin (R = 0,83; p < 0,0001). CONCLUSIONS: Fetuin A level monitoring is potentially a new marker for non-invasive and accurate prediction status for the hospitalization of patients with AP similar to other negative acute phase proteins like albumin.

[Role and indications of ERCP in treatment of acute biliary pancreatitis]. / Rola i miejsce EWCP w leczeniu ostrego zólciopochodnego zapalenia trzustki.

Results of endoscopic treatment of patients with biliary acute pancreatitis are presented. Initially this form of treatment was rather performed in the late period of the disease. After publication of the controlled randomized study by Neoptolemos and Carr-Locke'a, this method of the treatment was recommended in the early phase of the disease within the first 72 hours after hospital admission and only in patients with severe acute biliary pancreatitis. Recently, meta-analysis of controlled randomized studies restricted indications of this procedure only in patients with associated with acute cholangitis.

[Microcirculatory disturbance in the course of acute pancreatitis]. / Zaburzenia mikrokazenia w ostrym zapaleniu trzustki.

Although as many studies are sacrificed to acute pancreatitis (AP), the pathogenesis of the disease remains undiscovered. The microcirculatory disturbances during AP as a cause of necrotic changes in the parenchyma of the gland, described first time by Panum in 1886, have become again a very attractive theory. In the last decades, several studies were done to prove that microcirculatory impairment plays a crucial role in pathogenesis of severe AP. It had been proved that many mediators play important roles in this process including nitric oxide and endothelin balance. Vasoconstriction and vasodilatation named "vascular game" caused by cytokine accumulation and lower oxygenation of the tissue gives very interesting basis for theories about creating pancreatic necrosis. The severity of the course of AP also determinates damage of the microcirculation of the lungs, the liver and the bowels which leads to SIRS, MODS and MOF. The new experimental dates seems to be very promising and can became a basis for developing a new strategy of treatment in the most severe cases of AP. In this article we present up-to-date information about these theories and concepts.

[The role of nitric oxide (NO) in acute pancreatitis]. / Rola tlenku azotu w ostrym zapaleniu trzustki.

The hypothesis of the role of nitric oxide (NO) in acute pancreatitis (AP) is variable. According to some authors, increased level of nitric oxide has a positive influence on the course of AP. On the other hands, others show negative role of NO in this disease. NO plays many different roles in the organism. It regulates blood pressure, relaxes smooth muscle, plays a role in neurotransmition (for instance in specific and nonspecific immunological responses). NO regulates microcirculation within the pancreas and has an impact on the clinical courses of the mild as well as severe forms of the disease. It is also produced in the lungs alveoli and it is partly responsible for pulmonary complications of AP.

Blood serum levels of proinflammatory cytokines in patients with different degrees of biliary pancreatitis.

BACKGROUND: Proinflammatory cytokines play a fundamental role in the local and systemic inflammatory responses in the initial stages of acute biliary pancreatitis (ABP) and in the development of severe forms of the disease. OBJECTIVES: The aim of the present study was to assess the systemic release of proinflammatory cytokines and to characterize differences between patients with mild ABP (MABP) and severe ABP (SABP). PATIENTS AND METHODS: In the current study, 54 patients with MABP were compared with 14 patients with SABP. Serum levels of tumour necrosis factor-alpha, interleukin (IL)-1beta, IL-6, IL-8 and IL-12p40 were measured every second day after admission for one week. RESULTS: The tumour necrosis factor-alpha level was similar in all days of analysis in patients with MABP but was lower compared with SABP patients. The level of IL-1beta was higher at admission in patients with MABP. The level of IL-6 peaked on admission day in both groups, but in patients with SABP, the obtained values were higher. The level of IL-8 on admission day was slightly higher in patients with MABP and systematically decreased when measured on the following days (the third, fifth and seventh days of the study). An increased level of IL-8 during the third, fifth and seventh days of the investigation was seen in SABP patients. The level of IL-12p40 was slightly higher in patients with MABP on the day of admission. CONCLUSIONS: The levels of some proinflammatory cytokines are higher in patients with SABP than in patients with MABP. The most consistent difference between the two groups was that the levels of IL-6 were significantly higher in patients with SABP throughout the study. Serum concentration of IL-6 may be helpful as a marker of severity and outcome of ABP.

Comparison of sensitivity and specificity of serum poly-C avid ribonuclease activity and C-reactive protein concentration in detection of mild and severe acute pancreatitis.

The aim of this study was to compare diagnostic performance of C-reactive protein (CRP) and poly-C avid ribonuclease (P-RNase) levels in the prediction of a severe clinical course of acute pancreatitis (AP). The study included 36 patients with mild and 20 with severe AP. CRP concentration was measured by an immunonephelometric method and P-RNase activity by the rate of polycytidylate hydrolysis at pH 7.8. At the time of admission, both P-RNase and CRP levels were significantly increased in all patients when compared to healthy subjects (29.2 vs. 18.7 U/l and 91.1 vs. 2.89 mg/l; p < 0.001). Up to days 3 and 4 a further increase in P-RNase was observed. On the other hand, the increase in CRP continued only through days 2 and 3 (p < 0.001). Severe acute pancreatitis (SAP) and mild acute pancreatitis (MAP) differed significantly with respect to P-RNase levels on all days studied; whereas CRP levels differed significantly on days 2-5 but did not differ at admission. Receiver operating characteristic (ROC) curve function analysis yielded the best sensitivity of SAP detection for P-RNase, equaling 72.2%, at the cut-off point value 65.3 U/l on day 3 after admission. The sensitivity of CRP for detection of SAP was 85.0% at 125.7 mg/l on the 2nd day after admission. Both parameters studied were significantly associated with the severity of the AP clinical course; however, on days 1 and 2 post-admission, P-RNase was more specific for detection of SAP than CRP (94.4% vs. 77.1% on the 1st day and 94.4% vs. 55.5% on the 2nd day). In conclusion, P-RNase has shown an excellent performance for early differentiation of acute necrotizing pancreatitis.

[Acute pancreatitis in pregnant women--case reports]. / Ostre zapalenie trzustki u kobiet ciezarnych--opis przypadków.

Two patients with acute pancreatitis were presented. In the first case the disease occurred in the 32 week of pregnancy and in the perinatal period in second case. Some changes in lipid metabolism and composition of the bile in pregnant women and their role in pathogenesis of acute pancreatitis are discussed.

[Minimally invasive techniques in the treatment of acute biliary pancreatitis]. / Ostre zólciowe zapalenie trzustki leczone technikami maloinwazyjnymi.

43 cases of consecutive bilary acute pancreatitis were treated by early endoscopic sphincterotomy and laparoscopic cholecystectomy within first 48 hours after admission. The basic cause of disturbance of bile outflow was microlithiasis. Course of the disease was monitored by level of proinflammatory interleukins in the blood serum of analysed patients. Marked decrease of their level after endoscopic sphincterotomy was observed. This decrease was progressed after laparoscopic cholecystectomy followed by continuos closed lavage of abdominal cavity. Our results indicated that minimally invasive techniques should be done in the early stage of mild and moderate cases of acute biliary pancreatitis.