Superiority of Step-up Approach vs Open Necrosectomy in Long-term Follow-up of Patients With Necrotizing Pancreatitis.

BACKGROUND & AIMS: In a 2010 randomized trial (the PANTER trial), a surgical step-up approach for infected necrotizing pancreatitis was found to reduce the composite endpoint of death or major complications compared with open necrosectomy; 35% of patients were successfully treated with simple catheter drainage only. There is concern, however, that minimally invasive treatment increases the need for reinterventions for residual peripancreatic necrotic collections and other complications during the long term. We therefore performed a long-term follow-up study. METHODS: We reevaluated all the 73 patients (of the 88 patients randomly assigned to groups) who were still alive after the index admission, at a mean 86 months (±11 months) of follow-up. We collected data on all clinical and health care resource utilization endpoints through this follow-up period. The primary endpoint was death or major complications (the same as for the PANTER trial). We also measured exocrine insufficiency, quality of life (using the Short Form-36 and EuroQol 5 dimensions forms), and Izbicki pain scores. RESULTS: From index admission to long-term follow-up, 19 patients (44%) died or had major complications in the step-up group compared with 33 patients (73%) in the open-necrosectomy group (P = .005). Significantly lower proportions of patients in the step-up group had incisional hernias (23% vs 53%; P = .004), pancreatic exocrine insufficiency (29% vs 56%; P = .03), or endocrine insufficiency (40% vs 64%; P = .05). There were no significant differences between groups in proportions of patients requiring additional drainage procedures (11% vs 13%; P = .99) or pancreatic surgery (11% vs 5%; P = .43), or in recurrent acute pancreatitis, chronic pancreatitis, Izbicki pain scores, or medical costs. Quality of life increased during follow-up without a significant difference between groups. CONCLUSIONS: In an analysis of long-term outcomes of trial participants, we found the step-up approach for necrotizing pancreatitis to be superior to open necrosectomy, without increased risk of reinterventions.

Impact of characteristics of organ failure and infected necrosis on mortality in necrotising pancreatitis.

OBJECTIVE: In patients with pancreatitis, early persisting organ failure is believed to be the most important cause of mortality. This study investigates the relation between the timing (onset and duration) of organ failure and mortality and its association with infected pancreatic necrosis in patients with necrotising pancreatitis. DESIGN: We performed a post hoc analysis of a prospective database of 639 patients with necrotising pancreatitis from 21 hospitals. We evaluated the onset, duration and type of organ failure (ie, respiratory, cardiovascular and renal failure) and its association with mortality and infected pancreatic necrosis. RESULTS: In total, 240 of 639 (38%) patients with necrotising pancreatitis developed organ failure. Persistent organ failure (ie, any type or combination) started in the first week in 51% of patients with 42% mortality, in 13% during the second week with 46% mortality and in 36% after the second week with 29% mortality. Mortality in patients with persistent multiple organ failure lasting <1 week, 1-2 weeks, 2-3 weeks or longer than 3 weeks was 43%, 38%, 46% and 52%, respectively (p=0.68). Mortality was higher in patients with organ failure alone than in patients with organ failure and infected pancreatic necrosis (44% vs 29%, p=0.04). However, when excluding patients with very early mortality (within 10 days of admission), patients with organ failure with or without infected pancreatic necrosis had similar mortality rates (28% vs 34%, p=0.33). CONCLUSION: In patients with necrotising pancreatitis, early persistent organ failure is not associated with increased mortality when compared with persistent organ failure which develops further on during the disease course. Furthermore, no association was found between the duration of organ failure and mortality.

The Value of Decision Analytical Modeling in Surgical Research: An Example of Laparoscopic Versus Open Distal Pancreatectomy.

OBJECTIVE: To illustrate how decision modeling may identify relevant uncertainty and can preclude or identify areas of future research in surgery. SUMMARY BACKGROUND DATA: To optimize use of research resources, a tool is needed that assists in identifying relevant uncertainties and the added value of reducing these uncertainties. METHODS: The clinical pathway for laparoscopic distal pancreatectomy (LDP) versus open (ODP) for nonmalignant lesions was modeled in a decision tree. Cost-effectiveness based on complications, hospital stay, costs, quality of life, and survival was analyzed. The effect of existing uncertainty on the cost-effectiveness was addressed, as well as the expected value of eliminating uncertainties. RESULTS: Based on 29 nonrandomized studies (3.701 patients) the model shows that LDP is more cost-effective compared with ODP. Scenarios in which LDP does not outperform ODP for cost-effectiveness seem unrealistic, e.g., a 30-day mortality rate of 1.79 times higher after LDP as compared with ODP, conversion in 62.2%, surgically repair of incisional hernias in 21% after LDP, or an average 2.3 days longer hospital stay after LDP than after ODP. Taking all uncertainty into account, LDP remained more cost-effective. Minimizing these uncertainties did not change the outcome. CONCLUSIONS: The results show how decision analytical modeling can help to identify relevant uncertainty and guide decisions for future research in surgery. Based on the current available evidence, a randomized clinical trial on complications, hospital stay, costs, quality of life, and survival is highly unlikely to change the conclusion that LDP is more cost-effective than ODP.

Endoscopic or surgical step-up approach for infected necrotising pancreatitis: a multicentre randomised trial.

BACKGROUND: Infected necrotising pancreatitis is a potentially lethal disease and an indication for invasive intervention. The surgical step-up approach is the standard treatment. A promising alternative is the endoscopic step-up approach. We compared both approaches to see whether the endoscopic step-up approach was superior to the surgical step-up approach in terms of clinical and economic outcomes. METHODS: In this multicentre, randomised, superiority trial, we recruited adult patients with infected necrotising pancreatitis and an indication for invasive intervention from 19 hospitals in the Netherlands. Patients were randomly assigned to either the endoscopic or the surgical step-up approach. The endoscopic approach consisted of endoscopic ultrasound-guided transluminal drainage followed, if necessary, by endoscopic necrosectomy. The surgical approach consisted of percutaneous catheter drainage followed, if necessary, by video-assisted retroperitoneal debridement. The primary endpoint was a composite of major complications or death during 6-month follow-up. Analyses were by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN09186711. FINDINGS: Between Sept 20, 2011, and Jan 29, 2015, we screened 418 patients with pancreatic or extrapancreatic necrosis, of which 98 patients were enrolled and randomly assigned to the endoscopic step-up approach (n=51) or the surgical step-up approach (n=47). The primary endpoint occurred in 22 (43%) of 51 patients in the endoscopy group and in 21 (45%) of 47 patients in the surgery group (risk ratio [RR] 0·97, 95% CI 0·62-1·51; p=0·88). Mortality did not differ between groups (nine [18%] patients in the endoscopy group vs six [13%] patients in the surgery group; RR 1·38, 95% CI 0·53-3·59, p=0·50), nor did any of the major complications included in the primary endpoint. INTERPRETATION: In patients with infected necrotising pancreatitis, the endoscopic step-up approach was not superior to the surgical step-up approach in reducing major complications or death. The rate of pancreatic fistulas and length of hospital stay were lower in the endoscopy group. The outcome of this trial will probably result in a shift to the endoscopic step-up approach as treatment preference. FUNDING: The Dutch Digestive Disease Foundation, Fonds NutsOhra, and the Netherlands Organization for Health Research and Development.

Predicting a 'difficult cholecystectomy' after mild gallstone pancreatitis.

BACKGROUND: Cholecystectomy after gallstone pancreatitis may be technically demanding. The aim of this study was to investigate risk factors for a difficult cholecystectomy after mild pancreatitis. METHODS: This was a prospective study within a randomized controlled trial on the timing of cholecystectomy after mild gallstone pancreatitis. Difficulty of cholecystectomy was scored on a 0 to 10 visual analogue scale (VAS) by the senior attending surgeon. The primary outcome 'difficult cholecystectomy' was defined by presence of one or more of the following features: a VAS score ≥ 8, duration of surgery > 75 minutes, conversion or subtotal cholecystectomy. RESULTS: 249 patients were included in the primary analysis. A difficult cholecystectomy occurred in 82 patients (33%). In the 'same-admission cholecystectomy' group 29 of 112 cholecystectomies were difficult (26%) versus 49 of 127 patients (39%) who underwent surgery after 2 weeks (p = 0.037). After multivariable analysis, male sex (OR 1.80, 95% confidence interval [CI] 1.04-3.13; p = 0.037), prior sphincterotomy (OR 1.79, 95% CI 1.01-3.16; p = 0.046), and delaying cholecystectomy for at least two weeks (OR 1.81, 95% CI 1.04-3.16; p = 0.036) were independent predictors of a difficult cholecystectomy. CONCLUSION: Surgeons should anticipate a difficult cholecystectomy after mild gallstone pancreatitis in case of male sex, prior sphincterotomy and delayed cholecystectomy.

Minimally invasive and endoscopic versus open necrosectomy for necrotising pancreatitis: a pooled analysis of individual data for 1980 patients.

OBJECTIVE: Minimally invasive surgical necrosectomy and endoscopic necrosectomy, compared with open necrosectomy, might improve outcomes in necrotising pancreatitis, especially in critically ill patients. Evidence from large comparative studies is lacking. DESIGN: We combined original and newly collected data from 15 published and unpublished patient cohorts (51 hospitals; 8 countries) on pancreatic necrosectomy for necrotising pancreatitis. Death rates were compared in patients undergoing open necrosectomy versus minimally invasive surgical or endoscopic necrosectomy. To adjust for confounding and to study effect modification by clinical severity, we performed two types of analyses: logistic multivariable regression and propensity score matching with stratification according to predicted risk of death at baseline (low: <5%; intermediate: ≥5% to <15%; high: ≥15% to <35%; and very high: ≥35%). RESULTS: Among 1980 patients with necrotising pancreatitis, 1167 underwent open necrosectomy and 813 underwent minimally invasive surgical (n=467) or endoscopic (n=346) necrosectomy. There was a lower risk of death for minimally invasive surgical necrosectomy (OR, 0.53; 95% CI 0.34 to 0.84; p=0.006) and endoscopic necrosectomy (OR, 0.20; 95% CI 0.06 to 0.63; p=0.006). After propensity score matching with risk stratification, minimally invasive surgical necrosectomy remained associated with a lower risk of death than open necrosectomy in the very high-risk group (42/111 vs 59/111; risk ratio, 0.70; 95% CI 0.52 to 0.95; p=0.02). Endoscopic necrosectomy was associated with a lower risk of death than open necrosectomy in the high-risk group (3/40 vs 12/40; risk ratio, 0.27; 95% CI 0.08 to 0.88; p=0.03) and in the very high-risk group (12/57 vs 28/57; risk ratio, 0.43; 95% CI 0.24 to 0.77; p=0.005). CONCLUSION: In high-risk patients with necrotising pancreatitis, minimally invasive surgical and endoscopic necrosectomy are associated with reduced death rates compared with open necrosectomy.

Impact of Timing and Method of Virus Inoculation on the Severity of Wheat Streak Mosaic Disease.

Wheat streak mosaic virus (WSMV), transmitted by the wheat curl mite Aceria tosichella, frequently causes significant yield loss in winter wheat throughout the Great Plains of the United States. A field study was conducted in the 2013-14 and 2014-15 growing seasons to compare the impact of timing of WSMV inoculation (early fall, late fall, or early spring) and method of inoculation (mite or mechanical) on susceptibility of winter wheat cultivars Mace (resistant) and Overland (susceptible). Relative chlorophyll content, WSMV incidence, and yield components were determined. The greatest WSMV infection occurred for Overland, with the early fall inoculations resulting in the highest WSMV infection rate (up to 97%) and the greatest yield reductions relative to the control (up to 94%). In contrast, inoculation of Mace resulted in low WSMV incidence (1 to 28.3%). The findings from this study indicate that both method of inoculation and wheat cultivar influenced severity of wheat streak mosaic; however, timing of inoculation also had a dramatic influence on disease. In addition, mite inoculation provided much more consistent infection rates and is considered a more realistic method of inoculation to measure disease impact on wheat cultivars.

Colicky pain and related complications after cholecystectomy for mild gallstone pancreatitis.

BACKGROUND: Same-admission cholecystectomy is advised after gallstone pancreatitis to prevent recurrent pancreatitis, colicky pain and other complications, but data on the incidence of symptoms and complications after cholecystectomy are lacking. METHODS: This was a prospective cohort study during the previously published randomized controlled PONCHO trial on timing of cholecystectomy after mild gallstone pancreatitis. Data on healthcare consumption and questionnaires focusing on colicky pain and biliary complications were obtained during 6 months after cholecystectomy. Main outcomes were (i) postoperative colicky pain as reported in questionnaires and (ii) medical treatment for postoperative symptoms and gallstone related complications. RESULTS: Among 262 patients who underwent cholecystectomy after mild gallstone pancreatitis, 28 of 191 patients (14.7%) reported postoperative colicky pain. The majority of these were reported within 2 months after surgery and were single events. Overall, 25 patients (9.5%) required medical treatment for symptoms or gallstone related complications. Acute readmission was required in seven patients (2.7%). No predictors for the development of postoperative colicky pain were identified. DISCUSSION: Some 15% of patients experienced colicky pain after cholecystectomy for mild gallstone pancreatitis, which were mostly single events and rarely required readmission. These data may be used to better inform patients undergoing cholecystectomy for mild gallstone pancreatitis.

Seventeen-year Outcome of a Randomized Clinical Trial Comparing Laparoscopic and Conventional Nissen Fundoplication: A Plea for Patient Counseling and Clarification.

OBJECTIVE: To analyze long-term outcome of a randomized clinical trial comparing laparoscopic Nissen fundoplication (LNF) and conventional Nissen fundoplication (CNF) for the treatment of gastroesophageal reflux disease (GERD). BACKGROUND: LNF has replaced CNF, based on positive short and mid-term outcome. Studies with a follow-up of over 15 years are scarce, but are desperately needed for patient counselling. METHODS: Between 1997 and 1999, 177 patients with proton pump inhibitor (PPI)-refractory GERD were randomized to CNF or LNF. Data regarding the presence of reflux symptoms, dysphagia, general health, PPI use, and need for surgical reintervention at 17 years are reported. RESULTS: A total of 111 patients (60 LNF, 51 CNF) were included. Seventeen years after LNF and CNF, 90% and 95% of the patients reported symptom relief, with no differences in GERD symptoms or dysphagia. Forty-three and 49% of the patients used PPIs (NS). Both groups demonstrated significant improvement in general health (77% vs 71%; NS) and quality of life (75.3 vs 74.7; NS). Surgical reinterventions were more frequent after CNF (18% vs 45%; P = 0.002), mainly due to incisional hernia corrections (3% vs 14%; P = 0.047). CONCLUSIONS: The effects of LNF and CNF on symptomatic outcome and general state of health remain for up to 17 years after surgery, with no differences between the 2 procedures. CNF carries a higher risk of surgical reintervention, mainly due to incisional hernia corrections. Patients should be informed that 17 years after Nissen fundoplication, 60% of the patients are off PPIs, and 16% require reoperation for recurrent GERD and/or dysphagia.

Early versus on-demand nasoenteric tube feeding in acute pancreatitis.

BACKGROUND: Early enteral feeding through a nasoenteric feeding tube is often used in patients with severe acute pancreatitis to prevent gut-derived infections, but evidence to support this strategy is limited. We conducted a multicenter, randomized trial comparing early nasoenteric tube feeding with an oral diet at 72 hours after presentation to the emergency department in patients with acute pancreatitis. METHODS: We enrolled patients with acute pancreatitis who were at high risk for complications on the basis of an Acute Physiology and Chronic Health Evaluation II score of 8 or higher (on a scale of 0 to 71, with higher scores indicating more severe disease), an Imrie or modified Glasgow score of 3 or higher (on a scale of 0 to 8, with higher scores indicating more severe disease), or a serum C-reactive protein level of more than 150 mg per liter. Patients were randomly assigned to nasoenteric tube feeding within 24 hours after randomization (early group) or to an oral diet initiated 72 hours after presentation (on-demand group), with tube feeding provided if the oral diet was not tolerated. The primary end point was a composite of major infection (infected pancreatic necrosis, bacteremia, or pneumonia) or death during 6 months of follow-up. RESULTS: A total of 208 patients were enrolled at 19 Dutch hospitals. The primary end point occurred in 30 of 101 patients (30%) in the early group and in 28 of 104 (27%) in the on-demand group (risk ratio, 1.07; 95% confidence interval, 0.79 to 1.44; P=0.76). There were no significant differences between the early group and the on-demand group in the rate of major infection (25% and 26%, respectively; P=0.87) or death (11% and 7%, respectively; P=0.33). In the on-demand group, 72 patients (69%) tolerated an oral diet and did not require tube feeding. CONCLUSIONS: This trial did not show the superiority of early nasoenteric tube feeding, as compared with an oral diet after 72 hours, in reducing the rate of infection or death in patients with acute pancreatitis at high risk for complications. (Funded by the Netherlands Organization for Health Research and Development and others; PYTHON Current Controlled Trials number, ISRCTN18170985.).

Journal impact factor and methodological quality of surgical randomized controlled trials: an empirical study.

PURPOSE: The journal impact factor (IF) is often used as a surrogate marker for methodological quality. The objective of this study is to evaluate the relation between the journal IF and methodological quality of surgical randomized controlled trials (RCTs). METHODS: Surgical RCTs published in PubMed in 1999 and 2009 were identified. According to IF, RCTs were divided into groups of low (<2), median (2-3) and high IF (>3), as well as into top-10 vs all other journals. Methodological quality characteristics and factors concerning funding, ethical approval and statistical significance of outcomes were extracted and compared between the IF groups. Additionally, a multivariate regression was performed. RESULTS: The median IF was 2.2 (IQR 2.37). The percentage of 'low-risk of bias' RCTs was 13% for top-10 journals vs 4% for other journals in 1999 (P < 0.02), and 30 vs 12% in 2009 (P < 0.02). Similar results were observed for high vs low IF groups. The presence of sample-size calculation, adequate generation of allocation and intention-to-treat analysis were independently associated with publication in higher IF journals; as were multicentre trials and multiple authors. CONCLUSION: Publication of RCTs in high IF journals is associated with moderate improvement in methodological quality compared to RCTs published in lower IF journals. RCTs with adequate sample-size calculation, generation of allocation or intention-to-treat analysis were associated with publication in a high IF journal. On the other hand, reporting a statistically significant outcome and being industry funded were not independently associated with publication in a higher IF journal.

Effect of Temperature on Wheat Streak Mosaic Disease Development in Winter Wheat.

Temperature is one of the key factors that influence viral disease development in plants. In this study, temperature effect on Wheat streak mosaic virus (WSMV) replication and in planta movement was determined using a green fluorescent protein (GFP)-tagged virus in two winter wheat cultivars. Virus-inoculated plants were first incubated at 10, 15, 20, and 25°C for 21 days, followed by 27°C for 14 days; and, in a second experiment, virus-inoculated plants were initially incubated at 27°C for 3 days, followed by 10, 15, 20, and 25°C for 21 days. In the first experiment, WSMV-GFP in susceptible 'Tomahawk' wheat at 10°C was restricted at the point of inoculation whereas, at 15°C, the virus moved systemically, accompanied with mild symptoms, and, at 20 and 25°C, WSMV elicited severe WSMV symptoms. In resistant 'Mace' wheat (PI 651043), WSMV-GFP was restricted at the point of inoculation at 10 and 15°C but, at 20 and 25°C, the virus infected systemically with no visual symptoms. Some plants that were not systemically infected at low temperatures expressed WSMV-GFP in regrowth shoots when later held at 27°C. In the second experiment, Tomahawk plants (100%) expressed systemic WSMV-GFP after 21 days at all four temperature levels; however, systemic WSMV expression in Mace was delayed at the lower temperatures. These results indicate that temperature played an important role in WSMV replication, movement, and symptom development in resistant and susceptible wheat cultivars. This study also demonstrates that suboptimal temperatures impair WSMV movement but the virus rapidly begins to replicate and spread in planta under optimal temperatures.

Predicting Success of Catheter Drainage in Infected Necrotizing Pancreatitis.

INTRODUCTION: At least 30% of patients with infected necrotizing pancreatitis are successfully treated with catheter drainage alone. It is currently not possible to predict which patients also need necrosectomy. We evaluated predictive factors for successful catheter drainage. METHODS: This was a post hoc analysis of 130 prospectively included patients undergoing catheter drainage for (suspected) infected necrotizing pancreatitis. Using logistic regression, we evaluated the association between success of catheter drainage (ie, survival without necrosectomy) and 22 factors regarding demographics, disease severity (eg, Acute Physiology And Chronic Health Evaluation II score, organ failure), and morphologic characteristics on computed tomography (eg, percentage of necrosis). RESULTS: Catheter drainage was performed percutaneously in 113 patients and endoscopically in 17 patients. Infected necrosis was confirmed in 116 patients (89%). Catheter drainage was successful in 45 patients (35%). In multivariable regression, the following factors were associated with a reduced chance of success: male sex [odds ratio (OR) = 0.27; 95% confidence interval (CI): 0.09-0.55; P <0.01), multiple organ failure (OR = 0.15; 95% CI: 0.04-0.62; P < 0.01), percentage of pancreatic necrosis (<30%/30%-50%/>50%: OR = 0.54; 95% CI: 0.30-0.96; P = 0.03), and heterogeneous collection (OR = 0.21; 95% CI: 0.06-0.67; P < 0.01). A prediction model incorporating these factors demonstrated an area under the receiver operating characteristic curve of 0.76. A prognostic nomogram yielded success probability of catheter drainage from 2% to 91%. CONCLUSIONS: Male sex, multiple organ failure, increasing percentage of pancreatic necrosis and heterogeneity of the collection are negative predictors for success of catheter drainage in infected necrotizing pancreatitis. The constructed nomogram can guide prognostication in clinical practice and risk stratification in clinical studies.

Same-admission versus interval cholecystectomy for mild gallstone pancreatitis (PONCHO): a multicentre randomised controlled trial.

BACKGROUND: In patients with mild gallstone pancreatitis, cholecystectomy during the same hospital admission might reduce the risk of recurrent gallstone-related complications, compared with the more commonly used strategy of interval cholecystectomy. However, evidence to support same-admission cholecystectomy is poor, and concerns exist about an increased risk of cholecystectomy-related complications with this approach. In this study, we aimed to compare same-admission and interval cholecystectomy, with the hypothesis that same-admission cholecystectomy would reduce the risk of recurrent gallstone-related complications without increasing the difficulty of surgery. METHODS: For this multicentre, parallel-group, assessor-masked, randomised controlled superiority trial, inpatients recovering from mild gallstone pancreatitis at 23 hospitals in the Netherlands (with hospital discharge foreseen within 48 h) were assessed for eligibility. Adult patients (aged ≥18 years) were eligible for randomisation if they had a serum C-reactive protein concentration less than 100 mg/L, no need for opioid analgesics, and could tolerate a normal oral diet. Patients with American Society of Anesthesiologists (ASA) class III physical status who were older than 75 years of age, all ASA class IV patients, those with chronic pancreatitis, and those with ongoing alcohol misuse were excluded. A central study coordinator randomly assigned eligible patients (1:1) by computer-based randomisation, with varying block sizes of two and four patients, to cholecystectomy within 3 days of randomisation (same-admission cholecystectomy) or to discharge and cholecystectomy 25-30 days after randomisation (interval cholecystectomy). Randomisation was stratified by centre and by whether or not endoscopic sphincterotomy had been done. Neither investigators nor participants were masked to group assignment. The primary endpoint was a composite of readmission for recurrent gallstone-related complications (pancreatitis, cholangitis, cholecystitis, choledocholithiasis needing endoscopic intervention, or gallstone colic) or mortality within 6 months after randomisation, analysed by intention to treat. The trial was designed to reduce the incidence of the primary endpoint from 8% in the interval group to 1% in the same-admission group. Safety endpoints included bile duct leakage and other complications necessitating re-intervention. This trial is registered with Current Controlled Trials, number ISRCTN72764151, and is complete. FINDINGS: Between Dec 22, 2010, and Aug 19, 2013, 266 inpatients from 23 hospitals in the Netherlands were randomly assigned to interval cholecystectomy (n=137) or same-admission cholecystectomy (n=129). One patient from each group was excluded from the final analyses, because of an incorrect diagnosis of pancreatitis in one patient (in the interval group) and discontinued follow-up in the other (in the same-admission group). The primary endpoint occurred in 23 (17%) of 136 patients in the interval group and in six (5%) of 128 patients in the same-admission group (risk ratio 0·28, 95% CI 0·12-0·66; p=0·002). Safety endpoints occurred in four patients: one case of bile duct leakage and one case of postoperative bleeding in each group. All of these were serious adverse events and were judged to be treatment related, but none led to death. INTERPRETATION: Compared with interval cholecystectomy, same-admission cholecystectomy reduced the rate of recurrent gallstone-related complications in patients with mild gallstone pancreatitis, with a very low risk of cholecystectomy-related complications. FUNDING: Dutch Digestive Disease Foundation.

Risk of Recurrent Pancreatitis and Progression to Chronic Pancreatitis After a First Episode of Acute Pancreatitis.

BACKGROUND & AIMS: Patients with a first episode of acute pancreatitis can develop recurrent or chronic pancreatitis (CP). However, little is known about the incidence or risk factors for these events. METHODS: We performed a cross-sectional study of 669 patients with a first episode of acute pancreatitis admitted to 15 Dutch hospitals from December 2003 through March 2007. We collected information on disease course, outpatient visits, and hospital readmissions, as well as results from imaging, laboratory, and histology studies. Standardized follow-up questionnaires were sent to all available patients to collect information on hospitalizations and interventions for pancreatic disease, abdominal pain, steatorrhea, diabetes mellitus, medications, and alcohol and tobacco use. Patients were followed up for a median time period of 57 months. Primary end points were recurrent pancreatitis and CP. Risk factors were evaluated using regression analysis. The cumulative risk was assessed using Kaplan-Meier analysis. RESULTS: Recurrent pancreatitis developed in 117 patients (17%), and CP occurred in 51 patients (7.6%). Recurrent pancreatitis developed in 12% of patients with biliary disease, 24% of patients with alcoholic etiology, and 25% of patients with disease of idiopathic or other etiologies; CP occurred in 3%, 16%, and 10% of these patients, respectively. Etiology, smoking, and necrotizing pancreatitis were independent risk factors for recurrent pancreatitis and CP. Acute Physiology and Chronic Health Evaluation II scores at admission also were associated independently with recurrent pancreatitis. The cumulative risk for recurrent pancreatitis over 5 years was highest among smokers at 40% (compared with 13% for nonsmokers). For alcohol abusers and current smokers, the cumulative risks for CP were similar-approximately 18%. In contrast, the cumulative risk of CP increased to 30% in patients who smoked and abused alcohol. CONCLUSIONS: Based on a retrospective analysis of patients admitted to Dutch hospitals, a first episode of acute pancreatitis leads to recurrent pancreatitis in 17% of patients, and almost 8% of patients progress to CP within 5 years. Progression was associated independently with alcoholic etiology, smoking, and a history of pancreatic necrosis. Smoking is the predominant risk factor for recurrent disease, whereas the combination of alcohol abuse and smoking produces the highest cumulative risk for chronic pancreatitis.

Introgression of chromosome segments from multiple alien species in wheat breeding lines with wheat streak mosaic virus resistance.

Pyramiding of alien-derived Wheat streak mosaic virus (WSMV) resistance and resistance enhancing genes in wheat is a cost-effective and environmentally safe strategy for disease control. PCR-based markers and cytogenetic analysis with genomic in situ hybridisation were applied to identify alien chromatin in four genetically diverse populations of wheat (Triticum aestivum) lines incorporating chromosome segments from Thinopyrum intermedium and Secale cereale (rye). Out of 20 experimental lines, 10 carried Th. intermedium chromatin as T4DL*4Ai#2S translocations, while, unexpectedly, 7 lines were positive for alien chromatin (Th. intermedium or rye) on chromosome 1B. The newly described rye 1RS chromatin, transmitted from early in the pedigree, was associated with enhanced WSMV resistance. Under field conditions, the 1RS chromatin alone showed some resistance, while together with the Th. intermedium 4Ai#2S offered superior resistance to that demonstrated by the known resistant cultivar Mace. Most alien wheat lines carry whole chromosome arms, and it is notable that these lines showed intra-arm recombination within the 1BS arm. The translocation breakpoints between 1BS and alien chromatin fell in three categories: (i) at or near to the centromere, (ii) intercalary between markers UL-Thin5 and Xgwm1130 and (iii) towards the telomere between Xgwm0911 and Xbarc194. Labelled genomic Th. intermedium DNA hybridised to the rye 1RS chromatin under high stringency conditions, indicating the presence of shared tandem repeats among the cereals. The novel small alien fragments may explain the difficulty in developing well-adapted lines carrying Wsm1 despite improved tolerance to the virus. The results will facilitate directed chromosome engineering producing agronomically desirable WSMV-resistant germplasm.

Incidence of Wheat streak mosaic virus, Triticum mosaic virus, and Wheat mosaic virus in Wheat Curl Mites Recovered from Maturing Winter Wheat Spikes.

Wheat curl mites (WCM; Aceria tosichella) transmit Wheat streak mosaic virus (WSMV), Triticum mosaic virus (TriMV), and Wheat mosaic virus (WMoV) to wheat (Triticum aestivum L.) in the Great Plains region of the United States. These viruses can be detected in single, double, or triple combinations in leaf samples. Information on incidence of viruses in WCM at the end of the growing season is scant. The availability of this information can enhance our knowledge of the epidemiology of WCM-transmitted viruses. This research was conducted to determine the frequency of occurrence of WSMV, TriMV, and WMoV in WCM populations on field-collected maturing wheat spikes and to determine differences in WCM densities in three geographical regions (southeast, west-central, and panhandle) in Nebraska. Maturing wheat spikes were collected from 83 fields across Nebraska in 2011 and 2012. The spikes were placed in proximity to wheat seedlings (three- to four-leaf stage) in WCM-proof cages in a growth chamber and on sticky tape. WCM that moved off the drying wheat spikes in cages infested the wheat seedlings. WCM that moved off wheat spikes placed on sticky tape were trapped on the tape and were counted under a dissecting microscope. At 28 days after infestation, the wheat plants were tested for the presence of WSMV, TriMV, or WMoV using enzyme-linked immunosorbent assay and multiplex polymerase chain reaction. WSMV was the most predominant virus detected in wheat seedlings infested with WCM from field-collected spikes. Double (TriMV+WSMV or WMoV+WSMV) or triple (TriMV+ WMoV +WSMV) virus detections were more frequent (47%) than single detections (5%) of TriMV or WSMV. Overall, 81% of the wheat seedlings infested with WCM tested positive for at least one virus. No significant association (P > 0.05) was found between regions for WCM trapped on tape. These results suggest that WCM present on mature wheat spikes harbor multiple wheat viruses and may explain high virus incidence when direct movement of WCM into emerging winter wheat occurs in the fall.

Differential Transmission of Two Isolates of Wheat streak mosaic virus by Five Wheat Curl Mite Populations.

Wheat streak mosaic virus (WSMV), type member of the genus Tritimovirus in the family Potyviridae, is an economically important virus causing annual average yield losses of approximately 2 to 3% in winter wheat across the Great Plains. The wheat curl mite (WCM), Aceria tosichella, transmits WSMV along with two other viruses found throughout the Great Plains of the United States. Two common genotypes of WSMV (Sidney 81 and Type) in the United States share 97.6% nucleotide sequence identity but their transmission relationships with the WCM are unknown. The objective of this study was to determine transmission of these two isolates of WSMV by five WCM populations ('Nebraska', 'Montana', 'South Dakota', 'Type 1', and 'Type 2'). Nonviruliferous mites from each population were reared on wheat source plants mechanically inoculated with either Sidney 81 or Type WSMV isolates. For each source plant, individual mites were transferred to 10 separate test plants and virus transmission was determined by a double-antibody sandwich enzyme-linked immunosorbent assay. Source plants were replicated nine times for each treatment (90 individual mite transfers). Results indicate that three mite populations transmitted Sidney 81 at higher rates compared with Type. Two mite populations (Nebraska and Type 2) transmitted Sidney 81 and Type at higher rates compared with the other three populations. Results from this study demonstrate that interactions between virus isolates and mite populations influence the epidemiology of WSMV.

Diagnostic strategy and timing of intervention in infected necrotizing pancreatitis: an international expert survey and case vignette study.

BACKGROUND: The optimal diagnostic strategy and timing of intervention in infected necrotizing pancreatitis is subject to debate. We performed a survey on these topics amongst a group of international expert pancreatologists. METHODS: An online survey including case vignettes was sent to 118 international pancreatologists. We evaluated the use and timing of fine needle aspiration (FNA), antibiotics, catheter drainage and (minimally invasive) necrosectomy. RESULTS: The response rate was 74% (N = 87). None of the respondents use FNA routinely, 85% selectively and 15% never. Most respondents (87%) use a step-up approach in patients with infected necrosis. Walled-off necrosis (WON) is considered a prerequisite for endoscopic drainage and percutaneous drainage by 66% and 12%, respectively. After diagnosing infected necrosis, 55% routinely postpone invasive interventions, whereas 45% proceed immediately to intervention. Lack of consensus about timing of intervention was apparent on day 14 with proven infected necrosis (58% intervention vs. 42% non-invasive) as well as on day 20 with only clinically suspected infected necrosis (59% intervention vs. 41% non-invasive). DISCUSSION: The step-up approach is the preferred treatment strategy in infected necrotizing pancreatitis amongst expert pancreatologists. There is no uniformity regarding the use of FNA and timing of intervention in the first 2-3 weeks of infected necrotizing pancreatitis.

Admission Hematocrit and Rise in Blood Urea Nitrogen at 24 h Outperform other Laboratory Markers in Predicting Persistent Organ Failure and Pancreatic Necrosis in Acute Pancreatitis: A Post Hoc Analysis of Three Large Prospective Databases.

OBJECTIVES: Predicting severe acute pancreatitis (AP) remains a challenge. The present study compares admission blood urea nitrogen (BUN), hematocrit, and creatinine, as well as changes in their levels over 24 h, aiming to determine the most accurate laboratory test for predicting persistent organ failure and pancreatic necrosis. METHODS: Clinical data of 1,612 AP patients, enrolled prospectively in three independent cohorts (University of Pittsburgh, Brigham and Women's Hospital, Dutch Pancreatitis Study Group), were abstracted. The predictive accuracy of the studied laboratories was measured using area under the receiver-operating characteristic curve (AUC) analysis. A pooled analysis was conducted to determine their impact on the risk for persistent organ failure and pancreatic necrosis. Finally, a classification tree was developed on the basis of the most accurate laboratory parameters. RESULTS: Admission hematocrit ≥44% and rise in BUN at 24 h were the most accurate in predicting persistent organ failure (AUC: 0.67 and 0.71, respectively) and pancreatic necrosis (0.66 and 0.67, respectively), outperforming the other laboratory parameters and the acute physiology and chronic health evaluation-II score. In a pooled analysis, admission hematocrit ≥44% and rise in BUN at 24 h were associated with an odds ratio of 3.54 and 5.84 for persistent organ failure, and 3.11 and 4.07, respectively, for pancreatic necrosis. In addition, the classification tree illustrated that when both admission hematocrit was ≥44% and BUN levels increased at 24 h, the rates of persistent organ failure and pancreatic necrosis reached 53.6% and 60.3%, respectively. CONCLUSIONS: Admission hematocrit ≥44% and rise in BUN at 24 h may be the optimal predictive tools in clinical practice among existing laboratory parameters and scoring systems.