Association of cephalosporin resistance in intraoperative biliary cultures with surgical site infections in patients undergoing pancreaticoduodenectomy. A retrospective cohort study.

BACKGROUND: The aim of this study was to assess the incidence of bacterobilia at the time of a pancreaticoduodenectomy (PD) and the association of resistant bacteria in bile to surgical site infections (SSI). METHODS: This was a retrospective cohort study including patients undergoing PD in a single center between May 2016 and October 2020. Data of preoperative biliary drainage (PBD), intraoperative biliary cultures (IBC) and postoperative complications were analysed to assess the risk factors for resistant bacteria in IBC and SSIs. RESULTS: Of 361 patients included, 254 (70%) had undergone PBD. Second-generation cephalosporin resistant bacteria were found in IBC of 183 (64%) of all the patients. PBD was the only risk factor for second-generation cephalosporin resistance. The risk for second-generation cephalosporin resistance was more than 20-fold in patients with PBD [n = 170/254 (67%) (OR 22.58 (95% CI, 9.61-53.01), p < 0.001)] compared to patients who did not have PBD (n = 13/107 (12%)). Also, if the time between PBD and surgery was 2 months or more the second-generation cephalosporin resistance in IBC increased the risk for SSIs (OR 4.14 (95% CI, 1.18-14.51), p = 0.027). CONCLUSION: The second-generation cephalosporin resistance in IBC is common in patients who have undergone PBD. Broad-spectrum antibiotics in prophylaxis may be beneficial for these patients.

The first arriving virus shapes within-host viral diversity during natural epidemics.

Viral diversity has been discovered across scales from host individuals to populations. However, the drivers of viral community assembly are still largely unknown. Within-host viral communities are formed through co-infections, where the interval between the arrival times of viruses may vary. Priority effects describe the timing and order in which species arrive in an environment, and how early colonizers impact subsequent community assembly. To study the effect of the first-arriving virus on subsequent infection patterns of five focal viruses, we set up a field experiment using naïve Plantago lanceolata plants as sentinels during a seasonal virus epidemic. Using joint species distribution modelling, we find both positive and negative effects of early season viral infection on late season viral colonization patterns. The direction of the effect depends on both the host genotype and which virus colonized the host early in the season. It is well established that co-occurring viruses may change the virulence and transmission of viral infections. However, our results show that priority effects may also play an important, previously unquantified role in viral community assembly. The assessment of these temporal dynamics within a community ecological framework will improve our ability to understand and predict viral diversity in natural systems.

Strain Diversity and Spatial Distribution Are Linked to Epidemic Dynamics in Host Populations.

AbstractThe inherently variable nature of epidemics renders predictions of when and where infection is expected to occur challenging. Differences in pathogen strain composition, diversity, fitness, and spatial distribution are generally ignored in epidemiological modeling and are rarely studied in natural populations, yet they may be important drivers of epidemic trajectories. To examine how these factors are linked to epidemics in natural host populations, we collected epidemiological and genetic data from 15 populations of the powdery mildew fungus, Podosphaera plantaginis, on Plantago lanceolata in the Åland Islands, Finland. In each population, we tracked spatiotemporal disease progression throughout one epidemic season and coupled our survey of infection with intensive field sampling of the pathogen. We found that strain composition varied greatly among populations in the landscape. Within populations, strain composition was driven by the sequence of strain activity: early-active strains reached higher abundances, leading to consistent strain compositions over time. Co-occurring strains also varied in their contribution to the growth of the local epidemic, and these fitness inequalities were linked to epidemic dynamics: a higher proportion of hosts became infected in populations containing strains that were more similar in fitness. Epidemic trajectories in the populations were also linked to strain diversity and spatial dynamics: higher infection rates occurred in populations containing higher strain diversity, while spatially clustered epidemics experienced lower infection rates. Together, our results suggest that spatial and/or temporal variation in the strain composition, diversity, and fitness of pathogen populations are important factors generating variation in epidemiological trajectories among infected host populations.

Development and external validation of DISPAIR fistula risk score for clinically relevant postoperative pancreatic fistula risk after distal pancreatectomy.

BACKGROUND: Highly utilized risk scores for clinically relevant postoperative pancreatic fistula (CR-POPF) have guided clinical decision-making in pancreatoduodenectomy. However, none has been successfully developed for distal pancreatectomy. This study aimed to develop and validate a new fistula risk score for distal pancreatectomy. METHODS: Patients undergoing distal pancreatectomy at Helsinki University Hospital, Finland from 2013 to 2021, and at Karolinska University Hospital, Sweden, from 2010 to 2020, were included retrospectively. The outcome was CR-POPF, according to the 2016 International Study Group of Pancreatic Surgery definition. Preoperative clinical demographics and radiological parameters such as pancreatic thickness and duct diameter were measured. A logistic regression model was developed, internally validated with bootstrapping, and the performance assessed in an external validation cohort. RESULTS: Of 668 patients from Helsinki (266) and Stockholm (402), 173 (25.9 per cent) developed CR-POPF. The final model consisted of three variables assessed before surgery: transection site (neck versus body/tail), pancreatic thickness at transection site, and diabetes. The model had an area under the receiver operating characteristic curve (AUROC) of 0.904 (95 per cent c.i. 0.855 to 0.949) after internal validation, and 0.798 (0.748 to 0.848) after external validation. The calibration slope and intercept on external validation were 0.719 and 0.192 respectively. Four risk groups were defined in the validation cohort for clinical applicability: low (below 5 per cent), moderate (at least 5 but below 30 per cent), high (at least 30 but below 75 per cent), and extreme (75 per cent or more). The incidences in these groups were 8.7 per cent (11 of 126), 22.0 per cent (36 of 164), 63 per cent (57 of 91), and 81 per cent (17 of 21) respectively. CONCLUSION: The DISPAIR score after distal pancreatectomy may guide decision-making and allow a risk-adjusted outcome comparison for CR-POPF.

Long-term health-related quality of life in persons diagnosed with an insulinoma in Finland 1980-2010.

OBJECTIVE: Insulinomas are rare pancreatic neoplasms, which can usually be cured by surgery. As the diagnostic delay is often long and the prolonged hyperinsulinemia may have long-term effects on health and the quality of life, we studied the long-term health-related quality of life (HRQoL) in insulinoma patients. DESIGN, PATIENTS AND MEASUREMENTS: The HRQoL of adults diagnosed with an insulinoma in Finland in 1980-2010 was studied with the 15D instrument, and the results were compared to those of an age- and gender-matched sample of the general population. The minimum clinically important difference in the total 15D score has been defined as ±0.015. The clinical characteristics, details of insulinoma diagnosis and treatment, and the current health status of the subjects were examined to specify the possible determinants of long-term HRQoL. RESULTS: Thirty-eight insulinoma patients participated in the HRQoL survey (response rate 75%). All had undergone surgery with a curative aim, a median of 13 (min 7, max 34) years before the survey. The insulinoma patients had a clinically importantly and statistically significantly better mean 15D score compared with the controls (0.930 ± 0.072 vs 0.903 ± 0.039, P = .046) and were significantly better off regarding mobility, usual activities and eating. Among the insulinoma patients, younger age at the time of survey, higher level of education and smaller number of chronic diseases were associated with better overall HRQoL. CONCLUSIONS: In the long term, the overall HRQoL of insulinoma patients is slightly better than that of the general population.

Three-dimensional versus two-dimensional high-definition laparoscopy in transabdominal preperitoneal inguinal hernia repair: a prospective randomized controlled study.

BACKGROUND: Three-dimensional (3D) laparoscopy improves technical efficacy in laboratory environment, but evidence for clinical benefit is lacking. The aim of this study was to determine whether the 3D laparoscopy is beneficial in transabdominal preperitoneal laparoscopic inguinal hernia repair (TAPP). METHOD: In this prospective, single-blinded, single-center, superior randomized trial, patients scheduled for TAPP were randomly allocated to either 3D or two-dimensional (2D) TAPP laparoscopic approaches. Patients were excluded if secondary operation was planned, the risk of conversion was high, or the surgeon had less than five previous 3D laparoscopic procedures. Patients were operated on by 13 residents and 3 attendings. The primary endpoint was operation time. The study was registered in ClinicalTrials.gov (NCT02367573). RESULTS: Total 278 patients were randomized between 5th February 2015 and 23rd October 2017. Median operation time was shorter in the 3D group (56.0 min vs. 68.0 min, p < 0.001). 10 (8%) patients in 3D group and 6 (5%) patients in 2D group had clinically significant complications (Clavien-Dindo 2 or higher) (p = 0.440). Rate of hernia recurrence was similar between groups at 1-year follow-up. In the subgroup analyses, operation time was shorter in 3D laparoscopy among attendings, residents, female surgeons, surgeons with perfect stereovision, surgeons with > 50 3D laparoscopic procedures, surgeons with any experience in TAPP, patients with body mass indices < 30, and bilateral inguinal hernia repairs. CONCLUSION: 3D laparoscopy is beneficial and shortens operation time but does not affect safety or long-term outcomes of TAPP.

Scaling up the effects of inbreeding depression from individuals to metapopulations.

Inbreeding is common in nature, and many laboratory studies have documented that inbreeding depression can reduce the fitness of individuals. Demonstrating the consequences of inbreeding depression on the growth and persistence of populations is more challenging because populations are often regulated by density- or frequency-dependent selection and influenced by demographic and environmental stochasticity. A few empirical studies have shown that inbreeding depression can increase extinction risk of local populations. The importance of inbreeding depression at the metapopulation level has been conjectured based on population-level studies but has not been evaluated. We quantified the impact of inbreeding depression affecting the fitness of individuals on metapopulation persistence in heterogeneous habitat networks of different sizes and habitat configuration in a context of natural butterfly metapopulations. We developed a spatial individual-based simulation model of metapopulations with explicit genetics. We used Approximate Bayesian Computation to fit the model to extensive demographic, genetic and life-history data available for the well-studied Glanville fritillary butterfly (Melitaea cinxia) metapopulations in the Åland islands in SW Finland. We compared 18 semi-independent habitat networks differing in size and fragmentation. The results show that inbreeding is more frequent in small habitat networks, and consequently, inbreeding depression elevates extinction risks in small metapopulations. Metapopulation persistence and neutral genetic diversity maintained in the metapopulations increase with the total habitat amount in and mean patch size of habitat networks. Dispersal and mating behaviour interact with landscape structure to determine how likely it is to encounter kin while looking for mates. Inbreeding depression can decrease the viability of small metapopulations even when they are strongly influenced by stochastic extinction-colonization dynamics and density-dependent selection. The findings from this study support that genetic factors, in addition to demographic factors, can contribute to extinctions of small local populations and also of metapopulations.

Three-dimensional versus two-dimensional high-definition laparoscopy in cholecystectomy: a prospective randomized controlled study.

BACKGROUND: While 3D laparoscopy increases surgical performance under laboratory conditions, it is unclear whether it improves outcomes in real clinical scenarios. The aim of this trial was to determine whether the 3D laparoscopy can enhance surgical efficacy in laparoscopic cholecystectomy (LCC). METHOD: This prospective randomized controlled study was conducted between February 2015 and April 2017 in a day case unit of an academic teaching hospital. Patients scheduled for elective LCC were assessed for eligibility. The exclusion criteria were: (1) planned secondary operation in addition to LCC, (2) predicted to be high-risk for conversion, and (3) surgeons with less than five previous 3D laparoscopic procedures. Patients were operated on by 12 residents and 3 attendings. The primary endpoint was operation time. All surgeons were tested for stereoaquity (Randot® stereotest). The study was registered in ClinicalTrials.gov (NCT02357589). RESULTS: A total of 210 patients were randomized; 105 to 3D laparoscopy and 104 to 2D laparoscopy. Median operation time as similar in the 3D and 2D laparoscopy groups (49 min vs. 48 min, p = 0.703). Operation times were similar in subgroup analyses for surgeon's sex (male vs. female), surgeon's status (resident vs. attending), surgeon's stereovision (stereopsis 10 vs. less than 10), surgeon's experience (performed 200 LCCs or below versus over 200 LCCs), or patient's BMI (≤ 25 vs. 25-30 vs. > 30). No differences in intra- or postoperative complications were noted between the 3D and 2D groups. CONCLUSION: 3D laparoscopy did not show any advantages over 2D laparoscopy in LCC.

Predictable allele frequency changes due to habitat fragmentation in the Glanville fritillary butterfly.

Describing the evolutionary dynamics of now extinct populations is challenging, as their genetic composition before extinction is generally unknown. The Glanville fritillary butterfly has a large extant metapopulation in the Åland Islands in Finland, but declined to extinction in the nearby fragmented southwestern (SW) Finnish archipelago in the 20th century. We genotyped museum samples for 222 SNPs across the genome, including SNPs from candidate genes and neutral regions. SW Finnish populations had significantly reduced genetic diversity before extinction, and their allele frequencies gradually diverged from those in contemporary Åland populations over 80 y. We identified 15 outlier loci among candidate SNPs, mostly related to flight, in which allele frequencies have changed more than the neutral expectation. At outlier loci, allele frequencies in SW Finland shifted in the same direction as newly established populations deviated from old local populations in contemporary Åland. Moreover, outlier allele frequencies in SW Finland resemble those in fragmented landscapes as opposed to continuous landscapes in the Baltic region. These results indicate selection for genotypes associated with good colonization capacity in the highly fragmented landscape before the extinction of the populations. Evolutionary response to habitat fragmentation may have enhanced the viability of the populations, but it did not save the species from regional extinction in the face of severe habitat loss and fragmentation. These results highlight a potentially common situation in changing environments: evolutionary changes are not strong enough to fully compensate for the direct adverse effects of environmental change and thereby rescue populations from extinction.

Effect of spatial connectivity on host resistance in a highly fragmented natural pathosystem.

Both theory and experimental evolution studies predict migration to influence the outcome of antagonistic coevolution between hosts and their parasites, with higher migration rates leading to increased diversity and evolutionary potential. Migration rates are expected to vary in spatially structured natural pathosystems, yet how spatial structure generates variation in coevolutionary trajectories across populations occupying the same landscape has not been tested. Here, we studied the effect of spatial connectivity on host evolutionary potential in a natural pathosystem characterized by a stable Plantago lanceolata host network and a highly dynamic Podosphaera plantaginis parasite metapopulation. We designed a large inoculation experiment to test resistance of five isolated and five well-connected host populations against sympatric and allopatric pathogen strains, over 4 years. Contrary to our expectations, we did not find consistently higher resistance against sympatric pathogen strains in the well-connected populations. Instead, host local adaptation varied considerably among populations and through time with greater fluctuations observed in the well-connected populations. Jointly, our results suggest that in populations where pathogens have successfully established, they have the upper hand in the coevolutionary arms race, but hosts may be better able to respond to pathogen-imposed selection in the well-connected than in the isolated populations. Hence, the ongoing and extensive fragmentation of natural habitats may increase vulnerability to diseases.

The multivariate Wright-Fisher process with mutation: Moment-based analysis and inference using a hierarchical Beta model.

We consider the diffusion approximation of the multivariate Wright-Fisher process with mutation. Analytically tractable formulas for the first-and second-order moments of the allele frequency distribution are derived, and the moments are subsequently used to better understand key population genetics parameters and modeling frameworks. In particular we investigate the behavior of the expected homozygosity (the probability that two randomly sampled genes are identical) in the transient and stationary phases, and how appropriate the Dirichlet distribution is for modeling the allele frequency distribution at different evolutionary time scales. We find that the Dirichlet distribution is adequate for the pure drift model (no mutations allowed), but the distribution is not sufficiently flexible for more general mutation models. We suggest a new hierarchical Beta distribution for the allele frequencies in the Wright-Fisher process with a mutation model on the nucleotide level that distinguishes between transitions and transversions.

Inference on population histories by approximating infinite alleles diffusion.

Reconstruction of the past is an important task of evolutionary biology. It takes place at different points in a hierarchy of molecular variation, including genes, individuals, populations, and species. Statistical inference about population histories has recently received considerable attention, following the development of computational tools to provide tractable approaches to this very challenging problem. Here, we introduce a likelihood-based approach which generalizes a recently developed model for random fluctuations in allele frequencies based on an approximation to the neutral Wright-Fisher diffusion. Our new framework approximates the infinite alleles Wright-Fisher model and uses an implementation with an adaptive Markov chain Monte Carlo algorithm. The method is especially well suited to data sets harboring large population samples and relatively few loci for which other likelihood-based models are currently computationally intractable. Using our model, we reconstruct the global population history of a major human pathogen, Streptococcus pneumoniae. The results illustrate the potential to reach important biological insights to an evolutionary process by a population genetics approach, which can appropriately accommodate very large population samples.

Hierarchical and spatially explicit clustering of DNA sequences with BAPS software.

Phylogeographical analyses have become commonplace for a myriad of organisms with the advent of cheap DNA sequencing technologies. Bayesian model-based clustering is a powerful tool for detecting important patterns in such data and can be used to decipher even quite subtle signals of systematic differences in molecular variation. Here, we introduce two upgrades to the Bayesian Analysis of Population Structure (BAPS) software, which enable 1) spatially explicit modeling of variation in DNA sequences and 2) hierarchical clustering of DNA sequence data to reveal nested genetic population structures. We provide a direct interface to map the results from spatial clustering with Google Maps using the portal http://www.spatialepidemiology.net/ and illustrate this approach using sequence data from Borrelia burgdorferi. The usefulness of hierarchical clustering is demonstrated through an analysis of the metapopulation structure within a bacterial population experiencing a high level of local horizontal gene transfer. The tools that are introduced are freely available at http://www.helsinki.fi/bsg/software/BAPS/.

Two-phase importance sampling for inference about transmission trees.

There has been growing interest in the statistics community to develop methods for inferring transmission pathways of infectious pathogens from molecular sequence data. For many datasets, the computational challenge lies in the huge dimension of the missing data. Here, we introduce an importance sampling scheme in which the transmission trees and phylogenies of pathogens are both sampled from reasonable importance distributions, alleviating the inference. Using this approach, arbitrary models of transmission could be considered, contrary to many earlier proposed methods. We illustrate the scheme by analysing transmissions of Streptococcus pneumoniae from household to household within a refugee camp, using data in which only a fraction of hosts is observed, but which is still rich enough to unravel the within-household transmission dynamics and pairs of households between whom transmission is plausible. We observe that while probability of direct transmission is low even for the most prominent cases of transmission, still those pairs of households are geographically much closer to each other than expected under random proximity.

High immune cell infiltration predicts improved survival in cholangiocarcinoma.

Background: Antitumoral immune response has a crucial role in constraining cancer. However, previous studies on cholangiocarcinoma (CCA), a rare and aggressive cancer, have reported contradictory findings on the prognostic impact of tumor-infiltrating T-lymphocytes. We aimed to clarify the effect of tumor-infiltrating CD3+ and CD8+ lymphocytes and PD-1/PD-L1 expression on CCA prognosis. Methods: CD3+, CD8+, and PD-1+ lymphocyte densities, as well as PD-L1 expression rate were analyzed from stained tissue microarray samples from the tumor center and invasive margin of 47 cholangiocarcinomas. The association of CD3+ and CD8+ based Immune cell score (ICS) and its components with overall survival was evaluated, adjusting for age, sex, TNM stage, radicality of surgery, tumor location, and PD-L1 expression on immune cells. Results: Low ICS was a strong independent prognostic factor for worse overall survival (Hazard ratio 9.27, 95% confidence interval 2.72-31.64, P<0.001). Among the ICS components, high CD8+ lymphocyte infiltration at the tumor center had the most evident impact on patient outcome. PD-1 and PD-L1 expression on immune cells did not have a significant impact on overall survival alone; however, PD-L1 positivity seemed to impair survival for ICSlow subgroup. Conclusion: Identifying patient subgroups that could benefit from immunotherapy with PD-1/PD-L1 pathway blockade may help improve treatment strategies for this aggressive cancer. Our findings highlight the importance of evaluating the immune contexture in cholangiocarcinoma, as ICS serves as a strong independent prognostic and selective factor for patients who might benefit from immunotherapy.

[Intraductal papillary mucinous neoplasm of the pancreas, IPMN]. / Haiman intraduktaalinen papillaarinen musinoosinen neoplasia eli IPMN--pitäisikö leikata vai seurata?

With the development and increasing use of imaging techniques, intraductal papillary mucinous neoplasm (IPMN) is being detected with increasing frequency. Two forms of the disease are distinguished, the rare main duct form and the common accessory pancreatic duct form. The former often progresses to malignancy, the latter only seldom. The mixed form of IPMN exhibits features of both forms. In main duct IPMN, mucin production obstructs the pancreatic duct causing its dilatation and often symptoms typical of chronic pancreatitis. Main duct IPMN is always an indication for surgery, whereas monitoring is often sufficient for side duct IPMN.

Atlantic salmon (Salmo salar) age at maturity is strongly affected by temperature, population and age-at-maturity genotype.

Age at maturity is a key life history trait involving a trade-off between survival risk and reproductive investment, and is an important factor for population structures. In ectotherms, a warming environment may have a dramatic influence on development and life history, but this influence may differ between populations. While an increasing number of studies have examined population-dependent reactions with temperature, few have investigated this in the context of maturation timing. Atlantic salmon, a species of high conservation relevance, is a good study species for this topic as it displays considerable variation in age at maturity, of which a large proportion has been associated with a genomic region including the strong candidate gene vgll3. Until now, the effect of this gene in the context of different environments and populations has not been studied. Using a large-scale common-garden experiment, we find strong effects of temperature, population-of-origin, and vgll3 genotype on maturation in 2-year-old male Atlantic salmon (Salmo salar). With a temperature difference of 1.8°C, maturation probability was 4.8 times higher in the warm treatment than the cold treatment. This temperature effect was population-specific and was higher in the southern (60.48°N) compared to the northern (65.01°N) population. The early maturation vgll3*E allele was associated with a significantly higher maturation probability, but there was no vgll3 interaction with temperature or population. Both body condition and body mass associated with maturation. The body mass association was only present in the warm treatment. Our findings demonstrate that (i) populations can vary in their response to temperature change in terms of age at maturity, (ii) high intrinsic growth could be associated with higher thermal sensitivity for life history variation and (iii) vgll3 effects on age at maturity might be similar between populations and different thermal environments.

Reconstructing population histories from single nucleotide polymorphism data.

Population genetics encompasses a strong theoretical and applied research tradition on the multiple demographic processes that shape genetic variation present within a species. When several distinct populations exist in the current generation, it is often natural to consider the pattern of their divergence from a single ancestral population in terms of a binary tree structure. Inference about such population histories based on molecular data has been an intensive research topic in the recent years. The most common approach uses coalescent theory to model genealogies of individuals sampled from the current populations. Such methods are able to compare several different evolutionary scenarios and to estimate demographic parameters. However, their major limitation is the enormous computational complexity associated with the indirect modeling of the demographies, which limits the application to small data sets. Here, we propose a novel Bayesian method for inferring population histories from unlinked single nucleotide polymorphisms, which is applicable also to data sets harboring large numbers of individuals from distinct populations. We use an approximation to the neutral Wright-Fisher diffusion to model random fluctuations in allele frequencies. The population histories are modeled as binary rooted trees that represent the historical order of divergence of the different populations. A combination of analytical, numerical, and Monte Carlo integration techniques are utilized for the inferences. A particularly important feature of our approach is that it provides intuitive measures of statistical uncertainty related with the estimates computed, which may be entirely lacking for the alternative methods in this context. The potential of our approach is illustrated by analyses of both simulated and real data sets.

Prediction and consequences of postoperative pancreatitis after pancreaticoduodenectomy.

BACKGROUND: Recent studies have suggested postoperative acute pancreatitis (POAP) as a serious complication after pancreaticoduodenectomy (PD) and have speculated on its possible role in the pathogenesis of postoperative pancreatic fistula (POPF). This study aimed to assess the impact of POAP on post-PD outcomes and fistula risk score (FRS) performance in predicting POAP. METHODS: All PDs at Helsinki University Hospital between 2013 and 2020 were analysed. POAP was defined as a plasma amylase activity greater than the normal upper limit on postoperative day (POD) 1 and stratified as clinically relevant (CR)-POAP once C-reactive protein (CRP) reached or exceeded 180 mg/l, and non-CR-POAP once CRP was less than 180 mg/l on POD 2. The Comprehensive Complication Index (CCI) was used to assess total postoperative morbidity. Different FRSs were assessed using receiver operating characteristic curves. RESULTS: Of the 508 patients included, POAP occurred in 202 (39.8 per cent) patients, of whom 91 (17.9 per cent) had CR-POAP. The incidence of CR-POPF was 12.6 per cent (64 patients). Patients with non-CR-POAP had a similar morbidity to patients with no POAP (median CCI score 24.2 versus 22.6; P = 0.142), while CCI score was significantly higher (37.2) in patients with CR-POAP (P < 0.001). CR-POAP was associated with increased rates of CR-POPF, delayed gastric emptying, haemorrhage, and bile leak, while non-CR-POAP was associated only with CR-POPF. Ninety-day mortality was 1.6 per cent, 0.9 per cent, and 3.3 per cent in patients with no-POAP, non-CR-POAP, and CR-POAP, respectively. Updated alternative FRS showed the best performance in predicting CR-POAP (area under the curve 0.834). CONCLUSION: CR-POAP was associated with a higher CCI score, suggesting CR-POAP as a distinct entity from non-CR-POAP. FRSs can be used to assess the risk of CR-POAP.

Long-term morbidity and mortality in patients diagnosed with an insulinoma.

OBJECTIVE: Insulinomas are rare functional pancreatic neuroendocrine tumours. As previous data on the long-term prognosis of insulinoma patients are scarce, we studied the morbidity and mortality in the Finnish insulinoma cohort. DESIGN: Retrospective cohort study. METHODS: Incidence of endocrine, cardiovascular, gastrointestinal and psychiatric disorders, and cancers was compared in all the patients diagnosed with an insulinoma in Finland during 1980-2010 (n = 79, including two patients with multiple endocrine neoplasia type 1 syndrome), vs 316 matched controls, using the Mantel-Haenszel method. Overall survival was analysed with Kaplan-Meier and Cox regression analyses. RESULTS: The median length of follow-up was 10.7 years for the patients and 12.2 years for the controls. The long-term incidence of atrial fibrillation (rate ratio (RR): 2.07 (95% CI: 1.02-4.22)), intestinal obstruction (18.65 (2.09-166.86)), and possibly breast (4.46 (1.29-15.39) and kidney cancers (RR not applicable) was increased among insulinoma patients vs controls, P < 0.05 for all comparisons. Endocrine disorders and pancreatic diseases were more frequent in the patients during the first year after insulinoma diagnosis, but not later on. The survival of patients with a non-metastatic insulinoma (n = 70) was similar to that of controls, but for patients with distant metastases (n = 9), the survival was significantly impaired (median 3.4 years). CONCLUSIONS: The long-term prognosis of patients with a non-metastatic insulinoma is similar to the general population, except for an increased incidence of atrial fibrillation, intestinal obstruction, and possibly breast and kidney cancers. These results need to be confirmed in future studies. Metastatic insulinomas entail a markedly decreased survival.