Marco J. Bruno

Preoperative biliary drainage for cancer of the head of the pancreas

BACKGROUND The benefits of preoperative biliary drainage, which was introduced to improve the postoperative outcome in patients with obstructive jaundice caused by a tumor of the pancreatic head, are unclear. METHODS In this multicenter, randomized trial, we compared preoperative biliary drainage with surgery alone for patients with cancer of the pancreatic head. Patients with obstructive jaundice and a bilirubin level of 40 to 250 micromol per liter (2.3 to 14.6 mg per deciliter) were randomly assigned to undergo either preoperative biliary drainage for 4 to 6 weeks, followed by surgery, or surgery alone within 1 week after diagnosis. Preoperative biliary drainage was attempted primarily with the placement of an endoprosthesis by means of endoscopic retrograde cholangiopancreatography. The primary outcome was the rate of serious complications within 120 days after randomization. RESULTS We enrolled 202 patients; 96 were assigned to undergo early surgery and 106 to undergo preoperative biliary drainage; 6 patients were excluded from the analysis. The rates of serious complications were 39% (37 patients) in the early-surgery group and 74% (75 patients) in the biliary-drainage group (relative risk in the early-surgery group, 0.54; 95% confidence interval [CI], 0.41 to 0.71; P<0.001). Preoperative biliary drainage was successful in 96 patients (94%) after one or more attempts, with complications in 47 patients (46%). Surgery-related complications occurred in 35 patients (37%) in the early-surgery group and in 48 patients (47%) in the biliary-drainage group (relative risk, 0.79; 95% CI, 0.57 to 1.11; P=0.14). Mortality and the length of hospital stay did not differ significantly between the two groups. CONCLUSIONS Routine preoperative biliary drainage in patients undergoing surgery for cancer of the pancreatic head increases the rate of complications. (Current Controlled Trials number, ISRCTN31939699.)

Epidemiology, aetiology and outcome of acute and chronic pancreatitis: An update

Over the past decades several epidemiological studies have been published reporting on incidence trends, hospital admissions, etiological factors and outcome of both acute and chronic pancreatitis. Over time, the incidence of acute pancreatitis has increased in the Western countries. Also, the number of hospital admissions for both acute and chronic pancreatitis have increased. These upward time trends possibly reflect a change in the prevalence of main etiological factors (e.g. gallstones and alcohol consumption) and cofactors such as obesity and genetic susceptibility. Acute and chronic pancreatitis are associated with significant morbidity and mortality and a substantial use of health care resources. Although the case-fatality rate of acute pancreatitis decreased over time, the overall population mortality did not change for both acute and chronic pancreatitis. This chapter will focus on recent developments in the epidemiology, aetiology, natural course and outcome of both acute and chronic pancreatitis.

Palliation of patients with esophagogastric neoplasms by insertion of a covered expandable modified Gianturco-Z endoprosthesis: experiences in 153 patients☆☆☆

BACKGROUND We aimed to evaluate the short- and long-term outcomes of treatment by insertion of a covered expandable modified Gianturco-Z endoprosthesis (Song stent) in patients with esophagogastric malignancies. METHODS Consecutive patients with esophagogastric malignancies in whom a Song stent was inserted were included. Data were retrieved retrospectively. Dysphagia before and after stent placement was scored on a 5-point scale. Early (less than 30 days) and late complications (more than 30 days) were scored. RESULTS Analysis included 164 stents in 153 patients. Indications for stent placement were dysphagia and/or fistulas/perforations. The dysphagia score improved from a mean of 3.7 to 2.2 after stent placement (p < 0.0001). Fistulas/perforations sealed in 87% of cases. Early complications after stent placement occurred in 29.9% of cases. These included stent migration (4.3%), stent obstruction (6. 1%), aspiration pneumonia (4.9%), bleeding (4.3%), perforation (1. 8%), and pain (15.9%). Late complications occurred in 27.8% of cases. These included stent migration (2.6%), stent obstruction (9.6%), aspiration pneumonia (2.6%), bleeding (7.0%), perforation (0.9%), and pain (12.2%). The 30-day mortality was 26%. Death related to stent placement occurred in 3.3%. CONCLUSION Insertion of a Song expandable endoprosthesis in patients with esophagogastric malignancies significantly improves dysphagia, is successful in sealing fistulas/perforations, and is associated with acceptable morbidity and mortality rates.

Long-term results of endoscopic drainage of common bile duct strictures in chronic pancreatitis.

Objectives Endoscopic stent therapy is an established treatment modality for postoperative biliary strictures. At present, biliary stenting is also widely applied in chronic pancreatitis (CP), but results regarding long-term outcome are scarce. Methods All CP patients who underwent endoscopic biliary drainage of a benign stricture in our hospital between 1987 and 2000 were included in this retrospective study. Results Fifty-eight CP patients underwent biliary stenting (median age, 54 years; 44 male). The procedure-related mortality rate was 2% and the complication rate 4%. Median follow-up was 45 months (range, 0-182 months). Endoscopic treatment was successful in 22 patients (38%). Concomitant acute pancreatitis was the only factor identified as predictive of a successful outcome by multivariate analyses. Subanalysis of these 12 patients revealed a success rate of 92%, as opposed to 24% in cases without acute inflammation. In this latter group, continued stenting beyond a 1-year period almost never resulted in additional stricture resolvement. If stricture resolution was accomplished, however, no recurrences were observed. Conclusions For biliary strictures due to CP, without evidence of concomitant acute pancreatitis, the long-term success rate of endoscopic therapy is poor and only one out of four strictures is treated successfully. When a biliary stricture has not resolved after 1 year of endoscopic stenting, surgery should be considered.

Therapeutic delay and survival after surgery for cancer of the pancreatic head with or without preoperative biliary drainage.

Objective:To evaluate the relation between delay in surgery because of preoperative biliary drainage (PBD) and survival in patients scheduled for surgery for pancreatic head cancer. Background:Patients with obstructive jaundice due to pancreatic head cancer can undergo PBD. The associated delay of surgery can lead to more advanced cancer stages at surgical exploration, affecting resection rate and survival. Methods:We conducted a multicenter, randomized controlled clinical trial to compare PBD with early surgery (ES) for pancreatic head cancer for complications. We obtained Kaplan-Meier estimates of overall survival for patients with pathology-proven malignancy and compared survival functions of ES and PBD groups using log-rank test statistics. Multivariable Cox regression analyses were performed to evaluate the prognostic role of time to surgery for overall survival. Results:Mean times from randomization to surgery were 1.2 (0.9-1.5) and 5.1 (4.8-5.5) weeks in the ES and PBD groups, respectively (P < 0.001). In the ES group, 60 (67%) of 89 patients underwent resection, versus 53 (58%) of 91 patients in the PBD group (P = 0.20). Median survival after randomization was 12.2 (9.1-15.4) months in the ES group versus 12.7 (8.9-16.6) months in the PBD group (P = 0.91). A longer time to surgery was significantly associated with slightly lower mortality rate after surgery (hazard ratio = 0.90, 95% CI, 0.83-0.97), when taking into account resection, bilirubin, complications, pancreatic adenocarcinoma, tumor-positive lymph nodes, and microscopically residual disease. Conclusions:In patients with pancreatic head cancer, the delay in surgery associated with PBD does not impair or benefit survival rate.

Removable fully covered self-expandable metal stents in the treatment of common bile duct strictures due to chronic pancreatitis: A case series

The aim of this study was to test the removability of fully covered self-expandable metal stents (FCSEMS) in patients with a benign common bile duct (CBD) stricture. A FCSEMS was inserted in six patients with a CBD stricture due to chronic pancreatitis who were considered to be unfit for surgery, and stent removal was attempted after predefined intervals of 4 and 6 months. FCSEMS were successfully placed in all patients (100 % placement success) and stent extraction was accomplished in four patients (66 % removal rate), all of whom achieved stricture resolution (66 % resolution rate). In one patient a recurrent stenosis developed after 6 months (recurrence rate 25 %). Proximal stent migration occurred in two patients. In conclusion, FCSEMS removal was possible in the majority of patients and results regarding stricture dilation were promising. Nevertheless, before FCSEMS can become an acceptable treatment option for benign CBD strictures, innovative stent design modifications are necessary and removability must be ascertained.

Endoscopic ultrasound-guided fine-needle aspiration of pancreatic cystic lesions provides inadequate material for cytology and laboratory analysis: initial results from a prospective study

BACKGROUND AND STUDY AIMS Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is considered a valuable and safe technique for further investigation of pancreatic cystic lesions. In the framework of a prospective study on the accuracy of EUS-FNA we report our initial technical results regarding puncture access, sample adequacy, and complications PATIENTS AND METHODS Consecutive patients with indeterminate pancreatic cystic lesions underwent EUS and EUS-FNA. Pancreatic cyst fluid was collected for cytopathological analysis and measurement of amylase, carcinoembryonic antigen (CEA), and carbohydrate antigen 19.9 (CA 19.9) levels. Main outcome parameter for this analysis was the percentage of samples adequate for cytologic and laboratory analysis. RESULTS Of 143 patients (median age 63 years; median cyst size 2.8 cm) who underwent EUS, FNA was performed in 128 (90 %). The various reasons for not doing FNA included large distance between transducer and cystic lesion (n = 9), cyst not seen or too small (n = 2), and evident diagnosis not requiring FNA (n = 3). FNA was not possible in four patients (technical failures). Cyst fluid sent for cytology provided adequate cellular material in 44 cases only, accounting for an intention-to-diagnose yield of 31 % (44/143). Sufficient fluid for biochemical analysis was obtained in 68 cases (49 %). Complications occurred in three patients (2.4 %). CONCLUSIONS Although EUS-guided FNA was technically feasible in the majority of patients with pancreatic cystic lesions (87 %), it was possible to obtain a classifying cytopathologic diagnosis and a chemical analysis in only a third and a half of cases, respectively.

Practice and Yield of Early CT Scan in Acute Pancreatitis: A Dutch Observational Multicenter Study

Background: Early computed tomography (CT) (within 4 full days after symptom onset) may be performed to distinguish acute pancreatitis (AP) from other intra-abdominal conditions or to identify early pancreatic necrosis. We analyzed practice and yield of early CT in patients with an established clinical diagnosis of AP in a Dutch cohort (EARL study). Methods: Multicenter observational study. Etiology, disease course, CT timing, Balthazar CT score, and clinical management were evaluated. Results: First documented hospital admissions of 166 patients were analyzed. Etiology was biliary (42.8%), unknown (20.5%), alcoholic (18.1%), post-endoscopic retrograde cholangiopancreatography (11.4%), and miscellaneous (7.2%). In 89.2% (148/166), the disease course was mild. Out of 18 patients with severe AP, 11 eventually developed (peri)pancreatic necrosis. At least one CT (range 1–12) was performed in 47% (78/166) of all patients and in 62.8% (49/78) it was acquired within 4 full days after symptom onset. Practice, timing, and Balthazar CT score of early CTs were not significantly different between mild and severe AP. None of the early CTs showed necrosis and no alternative diagnoses were established. In 89.8% (44/49), clinical management was not altered after early CT. In 10.2% (5/49), prophylactic antibiotics were started, but in absence of necrosis. Conclusions: A CT scan was frequently acquired early in the course of AP, but its yield was low and had no implications with regard to clinical management. It seems prudent that clinicians should be more restrictive in the use of early CT, in particular in mild AP, to prevent unnecessary radiation exposure and to save costs.

Interobserver variation in the histopathological scoring of Helicobacter pylori related gastritis.

AIM: To test the reproducibility between two histopathologists of features of Helicobacter pylori gastritis, using the updated Sydney classification. METHODS: 290 dyspeptic Dutch patients with biopsy proven H pylori infection were enrolled in the study. Gastric antral mucosal biopsy specimens were analysed before and after H pylori eradication treatment. The biopsies were scored semi-quantitatively by two histopathologists, according to the updated Sydney classification system. Variables analysed included the density of H pylori infection, the degree of chronic inflammation, inflammatory activity, atrophy, intestinal metaplasia, and surface epithelial damage. Before grading biopsy specimens, both pathologists reached a consensus on the scoring of gastritis through interactive sessions using a multiheaded microscope. Subsequently all biopsy specimens were graded. Interobserver variability was also analysed using weighted kappa scores. RESULTS: For interobserver agreement on scoring the various gastritis features a high degree of reproducibility was reached overall. Agreement on grading of atrophy was the lowest; however, moderate to good reproducibility was achieved, with weighted kappa values of 0.49 in the pretreatment biopsies and 0.52 in the post-treatment biopsies. Disagreement was most common in biopsy specimens with lesser degrees of atrophy. A high degree of agreement was obtained for intestinal metaplasia, with weighted kappa values of 0.72 in the pretreatment biopsies and 0.73 in the post-treatment biopsies. The best agreement was reached in the assessment of the density of H pylori both before and after H pylori eradication treatment, with excellent weighted kappa values of 0.76 and 0.95, respectively. The grade of reproducibility of inflammatory activity, superficial epithelial damage, and chronic inflammation was high, with weighted kappa values varying from 0.60 to 0.76 and 0.62 to 0.83 before and after eradication, respectively. CONCLUSIONS: Reproducibility of grading H pylori related gastritis is high using the updated Sydney system. Despite the novel criteria for scoring atrophy, there was imperfect agreement on this feature between two independent histopathologists.

Incidence and mortality of acute and chronic pancreatitis in the Netherlands: A nationwide record-linked cohort study for the years 1995-2005

AIM To analyze trends in incidence and mortality of acute pancreatitis (AP) and chronic pancreatitis (CP) in the Netherlands and for international standard populations. METHODS A nationwide cohort is identified through record linkage of hospital data for AP and CP, accumulated from three nationwide Dutch registries: the hospital discharge register, the population register, and the death certificate register. Sex- and age-group specific incidence rates of AP and CP are defined for the period 2000-2005 and mortality rates of AP and CP for the period 1995-2005. Additionally, incidence and mortality rates over time are reported for Dutch and international (European and World Health Organization) standard populations. RESULTS Incidence of AP per 100000 persons per year increased between 2000 and 2005 from 13.2 (95%CI: 12.6-13.8) to 14.7 (95%CI: 14.1-15.3). Incidence of AP for males increased from 13.8 (95%CI: 12.9-14.7) to 15.2 (95%CI: 14.3-16.1), for females from 12.7 (95%CI: 11.9-13.5) to 14.2 (95%CI: 13.4-15.1). Irregular patterns over time emerged for CP. Overall mean incidence per 100000 persons per year was 1.77, for males 2.16, and for females 1.4. Mortality for AP fluctuated during 1995-2005 between 6.9 and 11.7 per million persons per year and was almost similar for males and females. Concerning CP, mortality for males fluctuated between 1.1 (95%CI: 0.6-2.3) and 4.0 (95%CI: 2.8-5.8), for females between 0.7 (95%CI: 0.3-1.6) and 2.0 (95%CI: 1.2-3.2). Incidence and mortality of AP and CP increased markedly with age. Standardized rates were lowest for World Health Organization standard population. CONCLUSION Incidence of AP steadily increased while incidence of CP fluctuated. Mortality for both AP and CP remained fairly stable. Patient burden and health care costs probably will increase because of an ageing Dutch population.