Juozas Pundzius

Value of the different prognostic systems and biological markers for predicting severity and progression of acute pancreatitis

Abstract Objective. Several tools have been developed for severity stratification in acute pancreatitis (AP). They include single biochemical markers and complex scoring systems, all of which aim at an early detection of severe AP to optimize monitoring and treatment of these patients. The aim of this study was to reassess and compare the value of some known and newly-introduced prognostic markers in the clinical context. Material and Methods. We have conducted a prospective observational study. One hundred and eight patients with a diagnosis of AP and onset of the disease within last 72 h were included in this study. Clinical data and expression results of some serum biochemical markers were used for statistical analysis. The diagnostic performance of scores predicting severity and progression of AP, cut-off values, specificity, and sensitivity were established using receiver operating characteristic curve analysis. Results. Among single biochemical markers, C-reactive protein remains the most useful. Despite its delayed increase, it is accurate, cheap, and widely available. Interleukin-6 and macrophage migration inhibitory factor seem to be new promising parameters for use in clinical routine. Pancreas specific scores (Imrie-Glasgow, pancreatitis outcome prediction) and scores assessing organ dysfunction (acute physiology and chronic health evaluation II, multiple organ dysfunction score, and Marshall score) remain of value in determining the severity, complications, and possible outcome of AP. Conclusions. Indication, timing, and consequences of the methods applied need to be carefully considered and incorporated into clinical assessments. Currently, there is no single prognostic marker that would cover the whole range of problems associated with the treatment of AP. The prediction of severity and progression of AP can be achieved using a series of accurate methods. The decision to undertake interventional or surgical treatment is the most complex task requiring both clinical judgment and meticulous monitoring of the patient.

Is transcatheter arterial embolization a safer alternative than surgery when endoscopic therapy fails in bleeding duodenal ulcer

Abstract Objective. Emergency surgery after unsuccessful endoscopic therapy for bleeding duodenal ulcer has been reported to have a high mortality. Transcatheter arterial embolization (TAE) of the gastroduodenal artery is an alternative strategy when endoscopic therapy fails. This study is a retrospective analysis comparing these two treatment strategies. Material and methods. Patients who underwent TAE (n = 24) or open surgery (n = 50) after unsuccessful endoscopic therapy for bleeding duodenal ulcers at two university hospitals between 2000 and 2007 were compared. Mortality, morbidity, length of hospital stay, age, number of endoscopic interventions and acute physiology and chronic health evaluation (APACHE) II score were evaluated. Results. The groups were comparable concerning gender and length of hospital stay. The mean age (69.6 ± 16.1 versus 61.9 ± 14.1 years; P = 0.043), APACHE II score (17.0 ± 5.1 versus 12.8 ± 5.7; P = 0.004) and number of gastroscopies (P = 0.009) were significantly higher in the embolization group. Five patients (20.8%) died in the embolization group compared to 11 (22%) in the surgery group. However, mortality in high-risk patients (APACHE II score ≥ 16.5) was lower in the TAE group (23.1% versus 50.0%; P = 0.236). Method-related as well as other complications were not significantly different between the two groups. There was, however, a higher re-bleeding rate in the TAE group. Conclusions. TAE of the gastroduodenal artery appears to be a safe alternative when endoscopic therapy for bleeding duodenal ulcer fails, at least in high-risk patients. The role of TAE in low-risk patients with bleeding from duodenal ulcer needs to be defined by means of a prospective controlled trial.

Whole Blood DNA Aberrant Methylation in Pancreatic Adenocarcinoma Shows Association with the Course of the Disease: A Pilot Study

Pancreatic tumors are usually diagnosed at an advanced stage in the progression of the disease, thus reducing the survival chances of the patients. Non-invasive early detection would greatly enhance therapy and survival rates. Toward this aim, we investigated in a pilot study the power of methylation changes in whole blood as predictive markers for the detection of pancreatic tumors. We investigated methylation levels at selected CpG sites in the CpG rich regions at the promoter regions of p16, RARbeta, TNFRSF10C, APC, ACIN1, DAPK1, 3OST2, BCL2 and CD44 in the blood of 30 pancreatic tumor patients and in the blood of 49 matching controls. In addition, we studied LINE-1 and Alu repeats using degenerate amplification approach as a surrogate marker for genome-wide methylation. The site-specific methylation measurements at selected CpG sites were done by the SIRPH method. Our results show that in the patient’s blood, tumor suppressor genes were slightly but significantly higher methylated at several CpG sites, while repeats were slightly less methylated compared to control blood. This was found to be significantly associated with higher risk for pancreatic ductal adenocarcinoma. Additionally, high methylation levels at TNFRSCF10C were associated with positive perineural spread of tumor cells, while higher methylation levels of TNFRSF10C and ACIN1 were significantly associated with shorter survival. This pilot study shows that methylation changes in blood could provide a promising method for early detection of pancreatic tumors. However, larger studies must be carried out to explore the clinical usefulness of a whole blood methylation based test for non-invasive early detection of pancreatic tumors.

Value of routine clinical tests in predicting the development of infected pancreatic necrosis in severe acute pancreatitis.

Objective. Fine-needle aspiration (FNA) is the procedure of choice for accurate diagnosis of infected necrosis. However, invasive procedures increase the risk of secondary pancreatic infection and the timing of FNA is still a matter for debate. Our objective was to assess the value of routine clinical tests to determine the minimal risk for infected necrosis, thereby optimizing timing and selection of patients for image-guided FNA. Material and methods. This prospective, non-randomized study comprised 90 patients with acute necrotizing pancreatitis. The data of 52 patients were used for discriminant function analysis to determine the differences between patients with infected necrosis and those with sterile necrosis. Cut-off points for variables were established using receiver operating characteristic (ROC) curve analysis and logistic regression was performed to determine the risk of infected necrosis. The clinical relevance of the defined diagnostic system was prospectively tested in a further 38 consecutive patients with acute necrotizing pancreatitis (ANP). Results. Discriminant function analysis showed that C-reactive protein (CRP) and white blood cell (WBC) values were significant discriminators between patients with sterile necrosis and those with infected necrosis. Cut-off values of 81 mg/l for CRP and 13×109/l for WBC were established. The predicted risk for infected necrosis is approx. 1.4% if both tests are below the defined cut-off values. Consequently, we found FNA unnecessary in this subset of patients, unless otherwise indicated, as this invasive procedure per se carries a certain risk of bacterial contamination. Conclusions. Routine clinical tests are helpful in diagnosing the development of infected necrosis. Based on the application of classification functions, the timing and selection of patients for image-guided FNA can be optimized.

Tumor‐related factors and patient's age influence survival after resection for ampullary adenocarcinoma

BACKGROUND/PURPOSE The majority of surgeons agree that ampullary adenocarcinoma should be removed by partial pancreatoduodenectomy. Favoring extended resection, based on the uncertainty of the preoperative diagnosis and the higher probability of clear resection margins, we aimed to disclose the results of this surgical procedure in terms of postoperative morbidity and mortality, and to identify prognosticators of long-term survival. METHODS We documented, prospectively, 25 consecutive patients with adenocarcinoma of the papilla of Vater in whom pylorus-preserving pancreatoduodenectomy was performed. Clinical data, pathology reports, International Union Against Cancer (UICC) tumor stage, postoperative morbidity, mortality, and long-term follow-up results were evaluated. The Kaplan-Meier method and log-rank test were applied for univariate analysis. The Cox proportional hazard model was used for multivariate analysis. RESULTS Postoperative mortality was 4%, overall morbidity was 32%, and pancreas-associated morbidity was 8%. Mean survival time was 53.8 months. Tumor size, N status, UICC stage, lymphatic invasion, blood vessel infiltration, R0 resection, and age of patient at the cutoff of 70 years were independent predictors of survival on univariate analysis. Multivariate analysis, however, disclosed no independent predictors of prognosis. CONCLUSIONS Pancreatoduodenectomy for ampullary carcinoma is reasonable in terms of postoperative morbidity and mortality. Tumor-related factors, R0 resection, and advanced age appeared as the main predictors of survival.

Increased postoperative peritoneal adhesion formation after the treatment of experimental peritonitis with chlorhexidine

Background and aimsChlorhexidine is known as a substance that produces adhesions. However, in an experimental model of peritoneal injury, lavage with chlorhexidine and saline solutions produced a similar number of adhesions. This study was designed to test the hypothesis that chlorhexidine gluconate 0.05% solution used for the treatment of peritonitis increases formation of postoperative peritoneal adhesions as compared to standard lavage with saline solution.Material and methodsForty Wistar rats were randomly allocated to gastric or faecal peritonitis groups. In each group rats were further randomly subdivided into saline or chlorhexidine peritoneal lavage groups. After 30 days the rats were killed and intraperitoneal adhesions were evaluated by adhesion score and grading.ResultsAdhesion scores were statistically significantly different between saline and chlorhexidine groups in both gastric and faecal peritonitis models. In the faecal peritonitis chlorhexidine group a 20% small bowel intussusception rate was observed, while there were no such complications in the other study groups. The conglomerate of organs formed by dense adhesions was present in 60% of cases when gastric peritonitis was lavaged by chlorhexidine and in only 10% when saline solution was used (P<0.05). Neither chlorhexidine nor saline solutions have caused such dense adhesions in faecal peritonitis.ConclusionPeritoneal lavage with chlorhexidine gluconate 0.05% solution in the treatment of experimental peritonitis results in increased adhesion formation.

Effects of prophylactic antibiotics in acute pancreatitis.

OBJECTIVES The use of prophylactic antibiotics in severe acute pancreatitis (SAP) is controversial. The aim of this study was to compare the effects of antibiotics administered as prophylaxis and as treatment on demand, respectively, in two prospective, non-randomized cohorts of patients. METHODS The study population consisted of 210 patients treated for SAP. In Group 1 (n= 103), patients received prophylactic antibiotics (ciprofloxacin, metronidazole). In Group 2 (n= 107), patients were treated on demand. Ultrasound-guided drainage and/or surgical debridement of infected necrosis were performed when the presence of infected pancreatic necrosis was demonstrated. The primary endpoints were infectious complication rate, need for and timing of surgical interventions, incidence of nosocomial infections and mortality rate. RESULTS Ultrasound-guided fine needle aspiration [in 18 (16.8%) vs. 13 (12.6%) patients; P= 0.714], ultrasound-guided drainage [in 15 (14.0%) vs. six (5.8%) patients; P= 0.065] and open surgical necrosectomy [in 10 (9.3%) vs. five (4.9%) patients; P= 0.206] were performed more frequently and earlier [at 16.6 ± 7.8 days vs. 17.2 ± 6.7 days (P= 0.723); at 19.5 ± 9.4 days vs. 24.5 ± 14.2 days (P= 0.498), and at 22.6 ± 13.5 days vs. 26.7 ± 18.1 days (P= 0.826), respectively] in Group 2 compared with Group 1. There were no significant differences between groups in mortality and duration of stay in the surgical ward or intensive care unit. CONCLUSIONS The results of this study support the suggestion that the use of prophylactic antibiotics does not affect mortality rate, but may decrease the need for interventional and surgical management, and lower the number of reoperations.

Fatty acids of erythrocyte membrane in acute pancreatitis patients

AIM To evaluate changes in the fatty acid composition of erythrocyte membrane phospholipids during severe and mild acute pancreatitis (AP) of alcoholic and nonalcoholic etiology. METHODS All consecutive patients with a diagnosis of AP and onset of the disease within the last 72 h admitted to the Hospital of Lithuanian University of Health Sciences between June and December 2007 were included. According to the Acute Physiology and Chronic Health Evaluation (APACHE II) scale, the patients were subdivided into the mild (APACHE II score < 7, n = 22) and severe (APACHE II score ≥ 7, n = 17) AP groups. Healthy individuals (n = 26) were enrolled as controls. Blood samples were collected from patients on admission to the hospital. Fatty acids (FAs) were extracted from erythrocyte phospholipids and expressed as percentages of the total FAs present in the chromatogram. The concentrations of superoxide dismutase and glutathione peroxidase were measured in erythrocytes. RESULTS We found an increase in the percentages of saturated and monounsaturated FAs, a decrease in the percentages of total polyunsaturated FAs (PUFAs) and n-3 PUFAs in erythrocyte membrane phospholipids of AP patients compared with healthy controls. Palmitic (C16:0), palmitoleic (C16:1n7cis), arachidonic (C20:4n6), docosahexaenoic (DHA, C22:6n3), and docosapentaenoic (DPA, C22:5n3) acids were the major contributing factors. A decrease in the peroxidation and unsaturation indexes in AP patients as well as the severe and mild AP groups as compared with controls was observed. The concentrations of antioxidant enzymes in the mild AP group were lower than in the control group. In severe AP of nonalcoholic etiology, the percentages of arachidic (C20:0) and arachidonic (C20:4n6) acids were decreased as compared with the control group. The patients with mild AP of nonalcoholic etiology had the increased percentages of total saturated FAs and gama linoleic acid (C18:3n6) and the decreased percentages of elaidic (C18:1n9t), eicosapentaenoic acid (EPA, C20:5n3), DPA (C22:5n3), DHA (C22:6n3) as well as total and n-3 PUFAs in erythrocyte membrane phospholipids. CONCLUSION The composition of FAs in erythrocyte membranes is altered during AP. These changes are likely to be associated with alcohol consumption, inflammatory processes, and oxidative stress.

Emergent pancreaticoduodenectomy: a dual institution experience and review of the literature

BACKGROUND Emergent pancreaticoduodenectomy (EPD) is an uncommon surgical procedure performed to treat patients with acute pancreaticoduodenal trauma, bleeding, or perforation. This study presents the experience of two university hospitals with EPD. METHODS Clinical data on EPD in trauma and nontrauma patients from 2002-2012 were extracted from the hepatopancreatobiliary surgery databases at Thomas Jefferson University and Kaunas Medical University Hospitals. Data on indications, perioperative variables, morbidity, and mortality rates were evaluated. RESULTS Ten single-stage EPD patients were identified. Five underwent a classic Whipple resection, whereas five had pylorus preservation. Seven patients had traumatic indications for pancreaticoduodenectomy: three from gunshot wounds to the abdomen and four from blunt high-energy injuries (two sustained injuries by falling from height and two by direct assaults on the abdomen). Three cases of nontrauma patients had EPD surgery for massive gastrointestinal hemorrhage. The median age of the EPD cohort was 46 y (range, 19-67 y). All 10 patients were recovered and were discharged from the hospital with a median postoperative length of stay of 24 d (range, 8-69 d). There were no perioperative mortalities. CONCLUSIONS Despite a high morbidity rate and prolonged recovery, this dual institutional review suggests that EPD can serve as a lifesaving procedure in both the trauma and the urgent nontrauma settings.

Heme oxygenase-1 gene promoter polymorphism is associated with the development of necrotizing acute pancreatitis.

Objectives Acute pancreatitis is a severe and frequently life-threatening disease, which can lead to pancreatic necrosis, acute lung injury, systemic inflammatory response syndrome, and other complications. In this study, we hypothesized that the expression of heme oxygenase-1 determined by the number of guanidinium thiocyanate (GT) repeats can influence the occurrence of acute pancreatitis. Methods Patients with acute pancreatitis (n = 131) and age- and sex-matched healthy controls (n = 108) were studied. The polymerase chain reaction products were analyzed by ABI 3130 genetic analyzer and the exact size of the polymerase chain reaction products was determined by GeneMapper software. A short allele was defined as containing 27 GT repeats or fewer, whereas a long allele was more than 27 repeats. Results The subjects were categorized into 3 groups on the basis of the genotype results: 1 short and 1 long, 2 short, and 2 long alleles (L/L). Patients with necrotizing disease more frequently were carriers of LL genotype compared with those who had edematous acute pancreatitis. Furthermore, logistic regression analysis revealed that the presence of L/L allele type doubles the risk for developing pancreatic necrosis in patients with acute pancreatitis. Conclusions The polymorphism of the GT repeats in the heme oxygenase-1 promoter region may be a risk factor for developing severe and necrotizing acute pancreatitis.