Waldemar Uhl

Acute Necrotizing Pancreatitis: Treatment Strategy According to the Status of Infection

ObjectiveTo determine benefits of conservative versus surgical treatment in patients with necrotizing pancreatitis. Summary Background DataInfection of pancreatic necrosis is the most important risk factor contributing to death in severe acute pancreatitis, and it is generally accepted that infected pancreatic necrosis should be managed surgically. In contrast, the management of sterile pancreatic necrosis accompanied by organ failure is controversial. Recent clinical experience has provided evidence that conservative management of sterile pancreatic necrosis including early antibiotic administration seems promising. MethodsA prospective single-center trial evaluated the role of nonsurgical management including early antibiotic treatment in patients with necrotizing pancreatitis. Pancreatic infection, if confirmed by fine-needle aspiration, was considered an indication for surgery, whereas patients without signs of pancreatic infection were treated without surgery. ResultsBetween January 1994 and June 1999, 204 consecutive patients with acute pancreatitis were recruited. Eighty-six (42%) had necrotizing disease, of whom 57 (66%) had sterile and 29 (34%) infected necrosis. Patients with infected necrosis had more organ failures and a greater extent of necrosis compared with those with sterile necrosis. When early antibiotic treatment was used in all patients with necrotizing pancreatitis (imipenem/cilastatin), the characteristics of pancreatic infection changed to predominantly gram-positive and fungal infections. Fine-needle aspiration showed a sensitivity of 96% for detecting pancreatic infection. The death rate was 1.8% (1/56) in patients with sterile necrosis managed without surgery versus 24% (7/29) in patients with infected necrosis (P <.01). Two patients whose infected necrosis could not be diagnosed in a timely fashion died while receiving nonsurgical treatment. Thus, an intent-to-treat analysis (nonsurgical vs. surgical treatment) revealed a death rate of 5% (3/58) with conservative management versus 21% (6/28) with surgery. ConclusionsThese results support nonsurgical management, including early antibiotic treatment, in patients with sterile pancreatic necrosis. Patients with infected necrosis still represent a high-risk group in severe acute pancreatitis, and for them surgical treatment seems preferable.

Gabexate mesilate in human acute pancreatitis

Abstract Background: A multicenter controlled study was performed to evaluate the effect of high doses of the low molecular weight protease inhibitor gabexate mesilate on mortality and complications associated with moderate and severe acute pancreatitis. Methods: Two hundred twenty-three patients from 29 hospitals were entered in the randomized, double-blind trial. Admission to the study was based on strict criteria excluding mild acute pancreatitis. The patients received placebo or 4 g gabexate mesilate per day intravenously for 7 days. All patients were followed up for 90 days after randomization. The analysis was based on 14 complications, including death. Results: There was no statistical difference in either mortality or complications associated with acute pancreatitis between the placeboand gabexate mesilate groups. Conclusions: The results show that gabexate mesilate was not effective in preventing complications and mortality in acute pancreatitis.

PMN-elastase in comparison with CRP, antiproteases, and LDH as indicators of necrosis in human acute pancreatitis.

We analyzed the role of polymorphonuclear granulocytes (PMN)-elastase in predicting the prognosis of patients with acute pancreatitis in comparison with C-reactive protein (CRP), lactate dehydrogenase (LDH), and the two antiproteases α1-antitrypsin (α1-AT) and α2-macroglobulin (α2-M). Fifty-two patients with acute pancreatitis were subdivided according to morphological criteria into 29 patients with edematous pancreatitis and 23 patients with necrotizing pancreatitis. Within 5 days after the onset of acute pancreatitis, the accuracy rates for detecting necrotizing pancreatitis were 86%, 84%, 82%, 72%, and 69%, using cutoff levels of 120 mg/L for CRP, 120 pg/L for PMN-elastase, 270 UIL for LDH, 1.5 g/L for α2-M, and 3.5 g/L for α1AT, respectively. The median peak value of PMN-elastase was reached on day 1 of acute pancreatitis in contrast to the median peak of CRP, which was at its highest between days 3 and 4. PMN-elastase represents a reliable indicator, comparable with CRP, for the staging of acute pancreatitis. The advantage of PMN-elastase over CRP appears to be its earlier increase and the greater dynamism of its serum course. Finally, the results suggest that CT scanning for the evaluation of the extent of intra- and extrapancreatic necrosis could be restricted to those patients with increased values of PMN-elastase and CRP.

Risk of Malignancy in Serous Cystic Neoplasms of the Pancreas

Background: In contrast to mucinous cystic neoplasms of the pancreas, which are known to have considerable malignant potential, the serous variant is generally thought to be benign. There are, however, several reports of malignancy in serous cystic neoplasms of the pancreas. Aims: To assess the risk of malignancy of serous cystic tumors of the pancreas and to investigate specific clinical and histological features. Methods: Clinical and pathological characteristics of benign and malignant serous cystic neoplasms of the pancreas were investigated by a review of the literature and documented by a case of a serous cystadenocarcinoma and immunohistochemical analysis of a series of serous cystadenomas. Reviewing the literature prevalence, age and sex distribution of serous cystic neoplasms were analyzed. Results: The prevalence of cancer among serous cystic neoplasms reported since 1989 was 3%. Serous cystadenoma of the pancreas present at an earlier age (61 years) than serous cystadenocarcinoma (66 years; p = 0.056) and are symptomatic in the majority of patients.Pathological examination of the primary tumor was not able to distinguish cystadenoma from cystadenocarcinoma in 38% of cases. In 25% the diagnosis of cancer was established only after growth of metachronous metastases. In the present case, nuclear atypia, papillary structures, proliferation marker Ki-67 and p53 protein were increased in the primary tumor and/or metachronous metastasis. Conclusion: Serous cystic neoplasms of the pancreas do have malignant potential with a risk of malignancy of 3% and should be surgically treated if the operative risk is acceptable. Routine analysis of genetic and proliferation markers may improve diagnosis of malignancy in these tumors.

Partial Pancreatectomy in Adult Humans Does Not Provoke β-Cell Regeneration

OBJECTIVE—β-Cell regeneration has been proposed as a possible treatment for diabetes, but the capacity for new β-cell formation in humans is yet unclear. In young rats, partial pancreatectomy prompts new β-cell formation to restore β-cell mass. We addressed the following questions: In adult humans: 1) Does partial pancreatectomy provoke new β-cell formation and increased β-cell mass? 2) Is β-cell turnover increased after partial pancreatectomy? RESEARCH DESIGN AND METHODS—Protocol 1: human pancreatic tissue was collected from 13 patients who underwent two consecutive partial pancreas resections, and markers of cell turnover were determined in both tissue samples, respectively. Protocol 2: pancreas volumes were determined from abdominal computer tomography scans, performed in 17 patients on two separate occasions after partial pancreatectomy. RESULTS—Protocol 1: fasting glucose concentrations increased significantly after the 50% pancreatectomy (P = 0.01), but the fractional β-cell area of the pancreas remained unchanged (P = 0.11). β-Cell proliferation, the overall replication index (Ki67 staining), and the percentage of duct cells expressing insulin were similar before and after the partial pancreatectomy. The overall frequency of apoptosis (terminal deoxynucleotidyl transferase biotin-dUTP nick-end labeling) was slightly increased following the partial pancreatectomy (P = 0.02). Protocol 2: pancreatic volume was ∼50% reduced to 35.6 ± 2.6 ccm3 by the partial pancreatectomy. The total pancreatic volume was unchanged after an interval of 247 ± 160 days (35.4 ± 2.7 ccm3; P = 0.51). CONCLUSIONS—Unlike in rodents, a 50% pancreatectomy does not prompt β-cell regeneration in adult humans. This explains the high incidence of diabetes after pancreatic resections. Such differences in β-cell turnover between rodents and humans should be born in mind when evaluating new treatment options aiming to restore β-cell mass in patients with diabetes.

Perspectives of Evidence-Based Surgery

The assessment of the optimal treatment option based on best current knowledge is called evidence-based medicine (EBM). Considering the cost explosion in public health systems, EBM should also incorporate proper utilization of the restricted economical resources and should enforce quality assurance in medicine. It is imperative that surgeons realize that randomized controlled trials are applicable to the operative specialties in a large scale, and are necessary to provide evidence-based surgery. So far, only 3.4% of all publications in the leading surgical journals are randomized controlled trials. Furthermore, only 44.1% of the published surgical randomized controlled studies compared different surgical procedures, whereas 55.9% of the articles compared medical therapies in surgical patients. Evidence-based surgical therapy is essential for further development of a high- quality surgical standard, which will also provide quality assurance in future surgical care. This article presents the definition of EBM and discusses specific problems involved in the introduction of its principles into the surgical discipline.

Influence of Etiology on the Course and Outcome of Acute Pancreatitis

It has been supposed that there are differences with regard to clinical course and outcome due to the underlying etiological factor in acute pancreatitis. Therefore, the objective of this study was to analyze the severity of the disease, serum enzymes, indicators of necrosis, systemic complications, and mortality in acute pancreatitis with regard to the etiology. One hundred ninety patients with acute pancreatitis (127 male, 63 female) were studied prospectively and subdivided into three etiological groups: (i) alcohol, (ii) gallstones, and (iii) other causes and idiopathic acute pancreatitis. Severity scores (Ranson and Bank) and findings by contrast-enhanced computed tomography were similar in all three groups. Analysis of serum enzymes [lipase, aspartate aminotransferase (ASAT)] and indicators of necrosis (C-reactive protein, alpha 1-antitrypsin, alpha 2-macroglobulin, and lactate dehydrogenase) showed only for ASAT within 24 h significantly higher levels in biliary acute pancreatitis in comparison with the other groups. There were no differences in the rate of infected pancreatic necrosis and mortality in alcohol-related acute pancreatitis (31 and 5.3%), biliary acute pancreatitis (38 and 10%) and acute pancreatitis due to other etiological factors (43 and 5.5%). In conclusion, this study clearly showed that once the pathogenetic mechanisms have initiated the disease, the course and outcome of acute pancreatitis are not influenced by the underlying etiological factor.

Pancreatic necrosis: an early finding in severe acute pancreatitis.

Despite the clinical importance of pancreatic necrosis in the course of acute pancreatitis, little is known about when it develops. Serum C-reactive protein (CRP) is a reliable parameter with a high detection rate for pancreatic necrosis. We analyzed 199 patients with acute pancreatitis. The development of pancreatic necrosis was ascertained by a daily measurement of serum CRP in 45 patients with contrast-enhanced computed tomographic proven necrotizing pancreatitis. In all 45 cases, the criteria for pancreatic necrosis were satisfied within the first 4 days of the onset of symptoms. This indicates that pancreatic necrosis is an early finding that develops within hours.

Stapler Hepatectomy is a Safe Dissection Technique: Analysis of 300 Patients

BackgroundIn many surgical procedures, stapling devices have been introduced for safety and to reduce the overall operative time. Their use for transection of hepatic parenchyma is not well established. Thus, the feasibility of stapler hepatectomy and a risk analysis of surgical morbidity based on intraoperative data have been prospectively assessed on a routine clinical basis.Materials and MethodsFrom October 1, 2001, to January 31, 2005, a total of 416 patients underwent liver resection in our department. During this period endo GIA vascular staplers were used for parenchymal transection in 300 cases of primary (22%) and metastatic (57%) liver cancer, benign diseases (adenoma, focal nodular hyperplasia [FNH], cysts) (14%), gallbladder carcinoma (2%), and other tumors (5%). There were 193 (64%) major resections (i.e., removal of three segments or more) and 107 minor hepatic resections. Additional extrahepatic resections were performed in 44 (15%) patients.ResultsMedian values for operative time and intraoperative hemorrhage were 210 minutes and 700 ml, respectively. Further, transfusion of RBC and FFP was needed in 17% and 11% of patients, respectively. A postoperative ICU stay for >2 days was required in 18% of patients. The median postoperative hospital stay was 10 days (IQR 8–14 days). The most frequent surgical complications were bile leak (8%), wound infection (3%), and pneumothorax (2%). In 7% of cases after stapler hepatectomy a relaparotomy was necessary. Treated medical complications were pleural effusion (7%), renal insufficiency (5%), and cardiac insufficiency (3%). Risk assessment revealed that both operative time and indication for resection had significant impact on surgical morbidity. Mortality (4%) and morbidity (33%) were comparable to other high-volume centers performing conventional liver resection techniques.ConclusionIn conclusion, stapler hepatectomy can be used in a routine clinical setting with a low incidence of surgical complications.

Useful markers for predicting severity and monitoring progression of acute pancreatitis.

Background: The main problem in staging acute pancreatitis is the lack of accurate predictors of disease severity and of markers for progression of acute pancreatitis. Methods: We reviewed the literature for all candidate markers of acute pancreatitis and graded their usefulness and practicability for prediction of severe pancreatitis and for monitoring disease progression. Results: Several markers can differentiate mild and severe cases of acute pancreatitis with a high positive predictive value. Trypsinogen activation peptide and procalcitonin show significant differences in patients with mild and severe disease already on admission. While most parameters peak early and decrease rapidly thereafter, C-reactive protein (CRP), phospholipase A2, procalcitonin and serum amyloid A are reliable predictors with persistently elevated levels in severe disease. CRP is still the reference parameter of all predictors indicating severe disease and pancreatic necrosis. So far, no single parameter has been developed which is suitable for early prediction of infected pancreatic necrosis. Conclusion: Of all markers available today, CRP is the ‘gold standard’ in predicting the severity of acute pancreatitis, but procalcitonin seems to be a promising tool to monitor the progression of the disease. CRP has already been established in clinical routine. For procalcitonin, a practicable assay is also available and could easily be adopted into clinical routine.