Kinetic studies of C1 and C2 Criegee intermediates with SO2 using laser flash photolysis coupled with photoionization mass spectrometry and time resolved UV absorption spectroscopy.

Recent, direct studies have shown that several reactions of stabilized Criegee intermediates (SCI) are significantly faster than indicated by earlier indirect measurements. The reaction of SCI with SO2 may contribute to atmospheric sulfate production, but there are uncertainties in the mechanism of the reaction of the C1 Criegee intermediate, CH2OO, with SO2. The reactions of C1, CH2OO, and C2, CH3CHOO, Criegee intermediates with SO2 have been studied by generating stabilized Criegee intermediates by laser flash photolysis (LFP) of RI2/O2 (R = CH2 or CH3CH) mixtures with the reactions being followed by photoionization mass spectrometry (PIMS). PIMS has been used to determine the rate coefficient for the reaction of CH3CHI with O2, k = (8.6 ± 2.2) × 10-12 cm3 molecule-1 s-1 at 295 K and 2 Torr (He). The yield of the C2 Criegee intermediate under these conditions is 0.86 ± 0.11. All errors in the abstract are a combination of statistical at the 1σ level and an estimated systematic contribution. For the CH2OO + SO2 reaction, additional LFP experiments were performed monitoring CH2OO by time-resolved broadband UV absorption spectroscopy (TRUVAS). The following rate coefficients have been determined at room temperature ((295 ± 2) K):CH2OO + SO2: k = (3.74 ± 0.43) × 10-11 cm3 molecule-1 s-1 (LFP/PIMS),k = (3.87 ± 0.45) × 10-11 cm3 molecule-1 s-1 (LFP/TRUVAS)CH3CHOO + SO2: k = (1.7 ± 0.3) × 10-11 cm3 molecule-1 s-1 (LFP/PIMS)LFP/PIMS also allows for the direction observation of CH3CHO production from the reaction of CH3CHOO with SO2, suggesting that SO3 is the co-product. For the reaction of CH2OO with SO2 there is no evidence of any variation in reaction mechanism with [SO2] as had been suggested in an earlier publication (Chhantyal-Pun et al., Phys. Chem. Chem. Phys., 2015, 17, 3617). A mean value of k = (3.76 ± 0.14) × 10-11 cm3 molecule-1 s-1 for the CH2OO + SO2 reaction is recommended from this and previous studies. The atmospheric implications of the results are briefly discussed.

Meeting report: consensus recommendations for a research agenda in exercise in solid organ transplantation.

With improved survival rates in solid organ transplantation there has been an increased focus on long-term outcomes following transplant, including physical function, health-related quality-of-life and cardiovascular mortality. Exercise training has the potential to affect these outcomes, however, research on the optimal timing, type, dose of exercise, mode of delivery and relevant outcomes is limited. This article provides a summary of a 2-day meeting held in April 2013 (Toronto, Canada) in which a multi-disciplinary group of clinicians, researchers, administrators and patient representatives engaged in knowledge exchange and discussion of key issues in exercise in solid organ transplant (SOT). The outcomes from the meeting were the development of top research priorities and a research agenda for exercise in SOT, which included the need for larger scale, multi-center intervention studies, development of standardized outcomes for physical function and surrogate measures for clinical trials, examining novel modes of exercise delivery and novel outcomes from exercise training studies such as immunity, infection, cognition and economic outcomes. The development and dissemination of "expert consensus guidelines," synthesizing both the best available evidence and expert opinion was prioritized as a key step toward improving program delivery.

Laparotomy for blunt abdominal trauma in a civilian trauma service.

This report looks at the group of patients who required a laparotomy for blunt torso trauma at a busy metropolitan trauma service in South Africa. Methods. A prospective trauma registry is maintained by the surgical services of the Pietermaritzburg metropolitan complex. This registry is interrogated retrospectively. All patients who required admission for blunt torso trauma over the period September 2006 - September 2007 were included for review. Proformas documenting mechanism of injury, age, vital signs, blood gas, delay in presentation, length of hospital stay, intensive care unit stay and operative details were completed. Results. A total of 926 patients were treated for blunt trauma by the Pietermaritzburg metropolitan services during the period under consideration. A cohort of 65 (8%) required a laparotomy for blunt trauma during this period. There were 17 females in this group. The mechanisms of injury were motor vehicle accident (MVA) (27), pedestrian vehicle accident (PVA) (21), assault (5), fall from a height (3), bicycle accident (6), quad bike accident (1) and tractor-related accident (2). The following isolated injuries were discovered at laparotomy: liver (9), spleen (5), diaphragm (1), duodenum (2), small bowel (8), mesentery (8) bladder (10), gallbladder (1), stomach (2), colon/rectum (2) and retrohepatic vena cava (1). The following combined injuries were discovered: liver and diaphragm (2), spleen and pancreas (1), spleen and liver (2), spleen, aorta and diaphragm (1), spleen and bladder (1) and small bowel and bladder (2). Eighteen patients in the series (26%) required relaparotomy. In 10 patients temporary abdominal containment was needed. The mortality rate was 26% (18 patients). There were 6 deaths from massive bleeding, all within 6 hours of operation, and 3 deaths from renal failure; the remaining 9 patients died of multiple organ failure. There were 8 negative laparotomies (7%). In the negative laparotomy group false-positive computed tomography (CT) scan findings were a problem in 3 cases, in 1 case hypotension and a fractured pelvis on admission prompted laparotomy, and in the other cases clinical findings prompted laparotomy. All patients who underwent negative laparotomy survived. There were 10 pelvic fractures, 5 lower limb fractures, 2 spinal injuries, 4 femur fractures and 2 upper limb fractures. CT scans were done in 25 patients. In 20 patients the systolic blood pressure on presentation was <90 mmHg and in 41 the pulse rate was >110 beats/min. In 16 patients there was a base excess of <-4 on presentation. Conclusion. Laparotomy is needed in less than 10% of patients who sustain blunt abdominal trauma. Solid visceral injury requiring laparotomy presents with haemodynamic instability. Hollow visceral injury has a more insidious presentation and is associated with a delay in diagnosis. CT scan is the most widely used investigation in blunt abdominal trauma. It is both sensitive and specific for solid visceral injury, but its accuracy for the diagnosis of hollow visceral injury is less well defined. Clinical suspicion must be high, and hollow visceral injury needs to be actively excluded.

Evaluating the potential utility of three-dimensional printed models in preoperative planning and patient consent in gastrointestinal cancer surgery.

INTRODUCTION: The Future of Surgery report from the Royal College of Surgeons of England acknowledges the important role that three-dimensional imaging will play in support of personalised surgical interventions. One component of this is preoperative planning. We investigated surgeons' and patients' perceptions of this evolving technology. MATERIALS AND METHODS: Ethical approval was obtained. From a normal computed tomography scan, three-dimensional models of the stomach, pancreas and rectum were rendered and printed on an Ultimaker™ three-dimensional printer. Semi-structured interviews were performed with surgeons and patients to explore perceived model effectiveness and utility. Likert scales were used to grade responses (1 = strongly disagree; 10 = strongly agree) and qualitative responses recorded. RESULTS: A total of 26 surgeons (9 rectal, 9 oesophagogastric, 8 pancreatic) and 30 patients (median age 62 years, interquartile range, IQR, 68-72 years; 57% male) were recruited. Median surgeon scores were effectiveness for preoperative planning, 6 (IQR 3-7), authenticity, 5 (IQR 3-6), likability, 6 (IQR 4-7), promoting learning, 7 (IQR 5-8), utility, 6 (IQR 5-7) and helping patients, 7 (IQR 5-8). Median patient scores were usefulness to the surgeon, 8 (IQR 7-9), authenticity, 8 (IQR 6-8), likability, 8 (IQR 7-8), helping understanding of condition, 8 (IQR 8-9), helping understanding of surgery, 8 (IQR 7-9) and feeling uncomfortable, 1 (IQR 1-4). Median overall decisional conflict score (0 = no; 100 = high) was 22 (IQR 19-28) and decision effectiveness was 25 (IQR 19-30). DISCUSSION: Overall, patients and surgeons considered that three-dimensional printed models were effective and had potential utility in education and, to a lesser extent, preoperative planning. Patient decisional conflict and effectiveness scores were weighted towards certainty in decision making but had room for improvement, which three-dimensional models may help to facilitate.

Hyaluronan binding function of CD44 is transiently activated on T cells during an in vivo immune response.

Though CD44 functions as a cell surface receptor for hyaluronan (HA) in some cell lines, most normal hematopoietic cells expressing CD44 do not bind HA. Certain CD44-specific monoclonal antibodies (mAbs) can rapidly induce CD44-mediated HA binding in normal murine T cells. This observation suggests that in vivo mechanisms may exist for activating the HA receptor function of CD44 on normal T cells. Here, it is shown that up to one third of splenic T cells are capable of CD44-mediated binding of fluorescein-conjugated HA (Fl-HA) during an in vivo allogeneic response. HA binding activity peaks at 7-8 d postinjection and declines rapidly. These rapid kinetics could be the result of transient activation of CD44 function and/or differentiation or expansion of short-lived population(s) that have constitutive HA-binding function. Both CD4 and CD8 T cells are included in the HA binding population which is strongly CD44 positive. After separation of HA-binding cells from nonbinding cells by cell sorting, it is shown that almost all cytotoxic effector cells are found in the HA-binding population. However, there is no evidence that CD44-mediated HA recognition is directly involved in the killing of target cells, since cytotoxicity could not be inhibited by CD44-specific mAbs that inhibit HA binding or by soluble HA. PCR amplification of cDNA reverse transcribed from RNA of sorted HA-binding cells indicated no evidence for CD44 isoforms other than the standard (hematopoietic) form. Though CD44 expression is known to be elevated upon T cell activation, and, as shown here, HA-binding function is induced in a portion of CD44-expressing T cells including cytotoxic effector cells, the role of CD44 and HA-recognition in immune responses is not known.

Endoscopic Botulinum toxin as a treatment for delayed gastric emptying following oesophagogastrectomy.

INTRODUCTION: The incidence of delayed gastric emptying (DGE) following oesophagogastrectomy with gastric conduit reconstruction is reported to be between 1.7% and 50%. This variation is due to differing practices of intraoperative pylorus drainage procedures, which increase the risk of postoperative biliary reflux and dumping syndrome, resulting in significant morbidity. The aim of our study was to establish rates of DGE in people undergoing oesophagogastrectomy without routine intraoperative drainage procedures, and to evaluate outcomes of postoperative endoscopically administered Botulinum toxin into the pylorus (EBP) for people with DGE resistant to systemic pharmacological treatment. METHODS: All patients undergoing oesophagogastrectomy between 1 January 2016 and 31 March 2018 at our unit were included. No intraoperative pyloric drainage procedures were performed, and DGE resistant to systemic pharmacotherapy was managed with EBP. RESULTS: Ninety-seven patients were included. Postoperatively, 29 patients (30%) were diagnosed with DGE resistant to pharmacotherapy. Of these, 16 (16.5%) were diagnosed within 30 days of surgery. The median pre-procedure nasogastric tube aspirate was 780ml; following EBP, this fell to 125ml (p<0.001). Median delay from surgery to EBP in this cohort was 13 days (IQR 7-16 days). Six patients required a second course of EBP, with 100% successful resolution of DGE before discharge. There were no procedural complications. CONCLUSIONS: This is the largest series of patients without routine intraoperative drainage procedures. Only 30% of patients developed DGE resistant to pharmacotherapy, which was managed safely with EBP in the postoperative period, thus minimising the risk of biliary reflux in people who would otherwise be at risk following prophylactic pylorus drainage procedures.

Variations in the pharmacological management of patients treated with carotid endarterectomy: a survey of European vascular surgeons.

OBJECTIVES: The peri-operative use of antiplatelet, anticoagulant and other drugs for patients undergoing carotid endarterectomy (CEA) is unclear and consensus is lacking. This study aimed to assess the current peri-operative practice of European vascular surgeons with respect to antiplatelet and other medications for patients undergoing CEA. DESIGN: Online questionnaire study. METHODS: Members of the Vascular Society of Great Britain & Ireland and European Society for Vascular Surgery were invited to complete an online survey in March 2008. Surgeons were asked about their preferences for the peri-operative administration of antiplatelet, statin and other medications for patients undergoing carotid endarterectomy. RESULTS: Partial or complete responses were received from 399/650 (61.4%) surgeons with a collective annual throughput of >11500 CEA procedures. For symptomatic and asymptomatic patients, 20/392 (5%) and 47/392 (12%) of surgeons would stop aspirin before surgery and 170/392 (43%) and 217/392 (55%) of surgeons would stop Clopidogrel prior to CEA. Of surgeons who would stop Clopidogrel, 84/170 (49%) and 124/217 (57%) would do so >7 days before surgery for symptomatic and asymptomatic patients respectively. 12/393 (3%) surgeons would prescribe one 75 mg dose of Clopidogrel on the evening before surgery. Intra-operative Dextran was used selectively by 40/395 (10%). Only 78/393 (20%) would delay surgery to commence a statin. Intra-operatively, 348/394 (88%) used intravenous heparin, which was reversed routinely by 47/348 (13%) and selectively by 60/348 (17%). CONCLUSIONS: There appears to be broad consensus between vascular surgeons in the pharmacological management of patients undergoing carotid endarterectomy, although some variations do exist. Further clinical studies may help clarify the optimum management strategy in this patient group.

Safety and effectiveness of antireflux surgery in obese patients.

Introduction The incidence of gastro-oesophageal reflux disease and obesity has increased significantly in recent years. The number of antireflux procedures being carried out on people with a higher body mass index (BMI) has been rising. Evidence is conflicting for outcomes of antireflux surgery in obese patients in terms of its safety and efficacy. Given the contradictory reports, this meta-analysis was undertaken to establish the outcomes of antireflux surgery (ARS) in obese patients and its associated safety. Methods A systematic electronic search was conducted using the PubMed, MEDLINE®, Ovid®, Cochrane Library and Google Scholar™ databases to identify studies that analysed the effect of BMI on the outcomes of ARS. A meta-analysis was performed using the random effects model. The intraoperative and postoperative outcomes that were examined included operative time, conversion to an open procedure, mean length of hospital stay, recurrence of acid reflux requiring reoperation and wrap migration. Results A total of 3,772 patients were included in 13 studies. There was no significant difference in procedure conversion rate, recurrence of reflux requiring reoperation or wrap migration between obese and non-obese patients. However, both the mean operative time and mean length of stay were longer for obese patients. Conclusions ARS in obese patients with gastro-oesophageal reflux disease is safe and outcomes are comparable with those in patients with a BMI in the normal range. A high BMI should therefore not be a deterrent to considering ARS for appropriate patients.

Surgery in the treatment of acute pancreatitis--minimal access pancreatic necrosectomy.

Between 5% and 10% of patients with acute pancreatitis will develop infected pancreatic necrosis. Traditional open surgery for this condition carries a mortality rate of up to 50%, and therefore a number of less invasive techniques have been developed, including radiological drainage and a minimal access retroperitoneal approach. No randomised controlled trials have been published which compare these techniques. Indications for minimal access surgery are the same as for open surgery, i.e. infected pancreatic necrosis or failure to improve with extensive sterile necrosis. Access is obtained to the pancreatic necrosis via the left loin and necrosectomy performed using an operating nephroscope, and this often requires several procedures to remove all necrotic tissue. The cavity is continuously irrigated on the ward in between procedures. The results of this approach are encouraging, with less systemic upset to the patient, a lower incidence of post-operative organ failure when compared with open surgery, and a reduced requirement for ITU support. There is also a trend towards a lower mortality rate, although this does not reach statistical significance on the data published so far. Current evidence suggests that a minimal access approach to pancreatic necrosis is feasible, well tolerated and beneficial for the patient when compared with open surgery.

Assessing the quality of written information provision for surgical procedures: a case study in oesophagectomy.

OBJECTIVE: To examine the content and quality of written information provided by surgical centres for patients undergoing oesophagectomy for cancer. DESIGN: Cross-sectional study of the content of National Health Service (NHS) patient information leaflets (PILs) about oesophageal cancer surgery, using a modified framework approach. DATA SOURCES: Written information leaflets from 41 of 43 cancer centres undertaking surgery for oesophageal cancer in England and Wales (response rate 95.3%). ELIGIBILITY CRITERIA: All English language versions of PILs about oesophagectomy. RESULTS: 32 different PILs were identified, of which 2 were generic tools (Macmillan 'understanding cancer of the gullet' and EIDO 'oesophagectomy'). Although most PILs focused on describing in-hospital adverse events, information varied widely and was often misleading. Just 1 leaflet described survival benefits of surgery and 2 mentioned the possibility of disease recurrence. CONCLUSIONS: Written information provided for patients by NHS cancer centres undertaking oesophagectomy is inconsistent and incomplete. It is recommended that surgeons work together with patients to agree on standards of information provision of relevance to all stakeholders' needs.

Outcome reporting in bariatric surgery: an in-depth analysis to inform the development of a core outcome set, the BARIACT Study.

Outcome reporting in bariatric surgery needs a core outcome set (COS), an agreed minimum set of outcomes reported in all studies of a particular condition. The aim of this study was to summarize outcome reporting in bariatric surgery to inform the development of a COS. Outcomes reported in randomized controlled trials (RCTs) and large non-randomized studies identified by a systematic review were listed verbatim and categorized into domains, scrutinizing the frequency of outcome reporting and uniformity of definitions. Ninety studies (39 RCTs) identified 1,088 separate outcomes, grouped into nine domains with most (n = 920, 85%) reported only once. The largest outcome domain was 'surgical complications', and overall, 42% of outcomes corresponded to a theme of 'adverse events'. Only a quarter of outcomes were defined, and where provided definitions, which were often contradictory. Percentage of excess weight loss was the main study outcome in 49 studies, but nearly 40% of weight loss outcomes were heterogeneous, thus not comparable. Outcomes of diverse bariatric operations focus largely on adverse events. Reporting is inconsistent and ill-defined, limiting interpretation and comparison of published studies. Thus, we propose and are developing a COS for the surgical treatment of severe and complex obesity.

Molecular pathogenesis of pancreatic ductal adenocarcinoma and clinical implications.

Pancreatic ductal adenocarcinoma (PDAC) is a significant cause of cancer death worldwide. PDAC is also one of the best-studied cancers with regard to molecular pathogenesis. The chief risk factors associated with PDAC are smoking and pancreatitis, in addition genetic predisposition seems to play a major role. This genetic predisposition may in some cases be indirect, for example via the elevated risk of pancreatitis seen in patients with hereditary pancreatitis (HP). The elucidation of the molecular causes of PDAC has enabled the provision of secondary screening for PDAC in conditions such as HP. This review is concerned with the molecular pathogenesis of PDAC and the application of this basic scientific understanding into state-of-the-art clinical practice.

Screening for early pancreatic ductal adenocarcinoma in hereditary pancreatitis.

Patients with hereditary pancreatitis have a 40% lifetime risk of developing pancreatic ductal adenocarcinoma. Existing methods of diagnosing pancreatic cancer such as tumor markers, endoscopy, and radiological imaging lack the sensitivity and specificity for early diagnosis, particularly in a background of chronic pancreatitis. Molecular based strategies offer new avenues of screening for pancreatic ductal adenocarcinoma in these high-risk patients, which may allow the development of highly sensitive and specific diagnostic tests for the early detection of cancer.

Reading disability subtypes and the test of memory and learning.

For Study 1, 24 readers with dysphonetic dyslexia and 21 with dyseidetic dyslexia, classified by Boder criteria, were compared to 90 control group participants (45 matched for age and 45 for reading level) on the Composite Memory Index (CMI) score from the Test of Memory and Learning (TOMAL). CMI scores were significantly lower for children with dyslexia (p <.0001). Plotting average subtest score profiles for all reader groups revealed auditory sequential memory impairments for both types of readers with dyslexia, and multiple strengths for good readers. Dysphonetic and dyseidetic dyslexia profiles were nearly identical. For Study 2, average linkage cluster analysis was performed using principal components derived from subtests of the TOMAL. Homogeneous clusters of normal readers and children with reading disabilities emerged. Results indicated that qualitatively distinct subtypes of readers with dyslexia exist.

Technology in the assessment of learning disability.

Recent neuroradiologic and brain imaging technologies, along with methods for displaying electrophysiologic data, have promulgated active exploration in the assessment of learning disability with attempts to improve diagnostic precision and elucidate the neurobiological substrates of learning disorders. The following article reviews these techniques and explores the research that has been conducted in this area over the past two decades. Initial investigations attempted to elucidate irregularities or abnormalities of brain morphology in individuals with learning disability utilizing computerized tomography (CT). The current standard for structural imaging of the brain is magnetic resonance (MR) imaging, which has allowed for greater specificity in identifying brain abnormalities. More recently, functional magnetic resonance imaging (fMRI) has been postulated as holding some promise in distinguishing anatomic/function differences in LD. Electrophysiological (EEG) and metabolic imaging techniques offer methods by which human brain activity can be studied during cognitive processes. Computerized EEG studies including evoked potentials (EP) or event-related potentials (ERP), spectral EEG analysis, and topographic EEG brain mapping have also identified a number of brain irregularities in individuals with learning disabilities, though no consistent exemplars have emerged. Studies with positron emission tomography (PET) and single photon emission computerized tomography (SPECT) have also demonstrated a number of abnormalities and inconsistencies in individuals with learning disabilities, but, again, no systematic research has demonstrated specific diagnostic abnormalities. Though inroads and some consistent patterns have begun to emerge in the assessment of learning disability with the preceding technologies, a number of challenges persist with neuroimaging and neurophysiological and metabolic imaging techniques. To date, no diagnostic conclusions have been drawn utilizing these methods in the assessment of the neurobiologic basis to LD.

The exercise-during-hemodialysis program: report on a pilot study.

Dialysis saves lives. However, dialysis alone cannot make those lives active and meaningful. Exercise, in particular, is critical in the rehabilitation of many individuals with chronic renal insufficiency The purpose of this pilot study was to: 1) examine changes in participants' physical capacity and quality of life with the intervention of a 12-week exercise program; 2) investigate whether erythropoietin (EPO) and antihypertensive medication dosages were reduced in the participants; 3) examine the feasibility of incorporating exercise into the London Health Sciences Centre (LHSC) hemodialysis program. A quasi-experimental one-group pre- and post-test design was utilized. Eight subjects completed the 12-week study. The exercise program involved a warm-up, stretching, strengthening, and cardiovascular training. The results demonstrated improvements in the participants'physical capacity, quality of life, and ability to perform activities of daily living (ADLs). There were no discernable trends in the participants' hemoglobin levels or EPO dosages. Although there were no statistically significant changes in participants' blood pressures, five out of the six participants who began the program on antihypertensive medications either had the dosages decreased or the drug(s) discontinued. Data from this small prospective study supports previous research that an exercise during dialysis program is safe and has the potential to result in positive patient outcomes.

The role of ultrasound in the management of patients with occult groin hernias.

INTRODUCTION: Groin ultrasound scanning is commonly used to examine patients with obscure groin pain or swelling. A recent study has shown ultrasound has a poor positive predictive value (PPV) in diagnosing groin hernias although earlier studies reported PPV values as high as 100%. Our aims were to calculate ultrasound's accuracy in diagnosing occult groin hernias in symptomatic patients and assess how management of these patients is affected by ultrasound result. METHODS: We retrospectively analysed 375 symptomatic adult patients, who between February 2008 and March 2010, had ultrasound to diagnose groin hernias when clinical examination was inconclusive. Patients were identified on a prospective radiology database and all groin ultrasounds were performed by either one consultant radiologist or one radiographer. RESULTS: Ultrasound was positive in 199 patients, of which 118 underwent surgery. Using operative findings as the gold standard, ultrasound's PPV for groin hernias was 70% (95% CI: 62-78%). Ultrasound was equivocal in 42 patients of which hernias were diagnosed in 7 of the 10 who had surgery. Ultrasound was negative in 151 patients of which none were later diagnosed with hernias during 3 years' median follow-up. CONCLUSION: Ultrasound is poor in diagnosing occult groin hernias with a PPV of 70% suggesting a 30% chance of negative groin exploration. The equivocal ultrasound group requires careful follow-up as a considerable number were later diagnosed with hernia. The absence of subsequent hernia diagnosis in the negative ultrasound group suggests it may be a useful rule-out test to exclude occult groin hernias in symptomatic patients.

Anticipation in familial pancreatic cancer.

BACKGROUND: Previous studies of anticipation in familial pancreatic cancer have been small and subject to ascertainment bias. Our aim was to determine evidence for anticipation in a large number of European families. PATIENTS AND METHODS: A total of 1223 individuals at risk from 106 families (264 affected individuals) were investigated. Generation G3 was defined as the latest generation that included any individual aged over 39 years; preceding generations were then defined as G2 and G1. RESULTS: With 80 affected child-parent pairs, the children died a median (interquartile range) of 10 (7, 14) years earlier. The median (interquartile range) age of death from pancreatic cancer was 70 (59, 77), 64 (57, 69), and 49 (44, 56) years for G1, G2, and G3, respectively. These indications of anticipation could be the result of bias. Truncation of Kaplan-Meier analysis to a 60 year period to correct for follow up time bias and a matched test statistic indicated significant anticipation (p=0.002 and p<0.001). To minimise bias further, an iterative analysis to predict cancer numbers was developed. No single risk category could be applied that accurately predicted cancer cases in every generation. Using three risk categories (low with no pancreatic cancer in earlier generations, high with a single earlier generation, and very high where two preceding generations were affected), incidence was estimated without significant error. Anticipation was independent of smoking. CONCLUSION: This study provides the first strong evidence for anticipation in familial pancreatic cancer and must be considered in genetic counselling and the commencement of secondary screening for pancreatic cancer.