Are parental condition transfer effects more widespread than is currently appreciated?

It has long been recognized that the environment experienced by parents can influence the traits of offspring (i.e. 'parental effects'). Much research has explored whether mothers respond to predictable shifts in environmental signals by modifying offspring phenotypes to best match future conditions. Many organisms experience conditions that theory predicts should favor the evolution of such 'anticipatory parental effects', but such predictions have received limited empirical support. 'Condition transfer effects' are an alternative to anticipatory effects that occur when the environment experienced by parents during development influences offspring fitness. Condition transfer effects occur when parents that experience high-quality conditions produce offspring that exhibit higher fitness irrespective of the environmental conditions in the offspring generation. Condition transfer effects are not driven by external signals but are instead a byproduct of past environmental quality. They are also likely adaptive but have received far less attention than anticipatory effects. Here, we review the generality of condition transfer effects and show that they are much more widespread than is currently appreciated. Condition transfer effects are observed across taxa and are commonly associated with experimental manipulations of resource conditions experienced by parents. Our Review calls for increased research into condition transfer effects when considering the role of parental effects in ecology and evolution.

Comparing brute force to transition path sampling for gas hydrate nucleation with a flat interface: comments on time reversal symmetry.

Fluid to solid nucleation is often investigated with the rare event method transition path sampling (TPS). I claim that the inherent irreversibility of solid nucleation, even at stationary conditions, calls into question TPS's applicability for determining solid nucleation mechanisms, especially for pre-critical behavior. Even when applied to a phenomenon which displays time reversal asymmetry like solid nucleation, TPS is a good means of exploring phase space and giving trends in post-critical structure, and its ability to facilitate nucleation rate and free energy calculations remains outstanding. Forward-only splitting and ratcheting methods such as forward flux sampling are more attractive for understanding nucleation mechanisms as they do not require time reversal symmetry, but at low driving forces may suffer from the same limitations as brute force: they may never make it to the first ratchet. Here I briefly summarize the TPS method and gas hydrate nucleation simulation literature, focusing on topics within both to facilitate a comparison of brute force hydrate nucleation to transition path sampling of hydrate nucleation. Perhaps anecdotally, the brute force technique results in more crystalline trajectories despite having higher driving forces than TPS. I maintain this difference is because of the inherent irreversibility of hydrate nucleation, meaning its pre-critical behavior cannot accurately be determined by the melting trajectories that comprise approximately half of the configurations in TPS's path ensemble.

Experimental test of the influence of light availability on the evolution of eye size and behaviour in Daphnia.

There exists extensive variation in eye size. Much work has provided a connection between light availability and differences in eye size across taxa. Experimental tests of the role of the light environment on the evolution of eye size are lacking. Here, we performed a selection experiment that examined the influence of light availability on shifts in eye size and the connection between eye size and phototactic (anti-predator) behaviour in Daphnia. We set-up replicate experimental populations of Daphnia, repeatedly evaluated phenotypic shifts in eye size during the ~50-day experiment, and performed a common garden experiment at the end of the experiment to test for evolutionary shifts in eye size and behaviour. Our phenotypic analyses showed that eye size rapidly diverged between the light treatments; relative eye size was consistently larger in the low versus high light treatments. Selection on eye size was also modified by variation in density as increases in Daphnia density favoured a larger eye. However, we did not observe differences in eye size between the light treatments following two generations of common garden rearing at the end of the experiment. We instead observed strong shifts in anti-predator behaviour. Daphnia from the low light treatment exhibited decreased phototactic responses to light. Our results show that decreased light relaxes selection on anti-predator behaviour. Such trends provide new insights into selection on eye size and behaviour.

SHock-INduced Endotheliopathy (SHINE): A mechanistic justification for viscoelastography-guided resuscitation of traumatic and non-traumatic shock.

Irrespective of the reason for hypoperfusion, hypocoagulable and/or hyperfibrinolytic hemostatic aberrancies afflict up to one-quarter of critically ill patients in shock. Intensivists and traumatologists have embraced the concept of SHock-INduced Endotheliopathy (SHINE) as a foundational derangement in progressive shock wherein sympatho-adrenal activation may cause systemic endothelial injury. The pro-thrombotic endothelium lends to micro-thrombosis, enacting a cycle of worsening perfusion and increasing catecholamines, endothelial injury, de-endothelialization, and multiple organ failure. The hypocoagulable/hyperfibrinolytic hemostatic phenotype is thought to be driven by endothelial release of anti-thrombogenic mediators to the bloodstream and perivascular sympathetic nerve release of tissue plasminogen activator directly into the microvasculature. In the shock state, this hemostatic phenotype may be a counterbalancing, yet maladaptive, attempt to restore blood flow against a systemically pro-thrombotic endothelium and increased blood viscosity. We therefore review endothelial physiology with emphasis on glycocalyx function, unique biomarkers, and coagulofibrinolytic mediators, setting the stage for understanding the pathophysiology and hemostatic phenotypes of SHINE in various etiologies of shock. We propose that the hyperfibrinolytic phenotype is exemplified in progressive shock whether related to trauma-induced coagulopathy, sepsis-induced coagulopathy, or post-cardiac arrest syndrome-associated coagulopathy. Regardless of the initial insult, SHINE appears to be a catecholamine-driven entity which early in the disease course may manifest as hyper- or hypocoagulopathic and hyper- or hypofibrinolytic hemostatic imbalance. Moreover, these hemostatic derangements may rapidly evolve along the thrombohemorrhagic spectrum depending on the etiology, timing, and methods of resuscitation. Given the intricate hemochemical makeup and changes during these shock states, macroscopic whole blood tests of coagulative kinetics and clot strength serve as clinically useful and simple means for hemostasis phenotyping. We suggest that viscoelastic hemostatic assays such as thromboelastography (TEG) and rotational thromboelastometry (ROTEM) are currently the most applicable clinical tools for assaying global hemostatic function-including fibrinolysis-to enable dynamic resuscitation with blood products and hemostatic adjuncts for those patients with thrombotic and/or hemorrhagic complications in shock states.

Transplant experiments demonstrate that larger brains are favoured in high-competition environments in Trinidadian killifish.

The extent to which the evolution of a larger brain is adaptive remains controversial. Trinidadian killifish (Anablepsoides hartii) are found in sites that differ in predation intensity; fish that experience decreased predation and increased intraspecific competition exhibit larger brains. We evaluated the connection between brain size and fitness (survival and growth) when killifish are found in their native habitats and when fish are transplanted from sites with predators to high-competition sites that lack predators. Selection for a larger brain was absent within locally adapted populations. Conversely, there was a strong positive relationship between brain size and growth in transplanted but not resident fish in high-competition environments. We also observed significantly larger brain sizes in the transplanted fish that were recaptured at the end of the experiment versus those that were not. Our results provide experimental support that larger brains increase fitness and are favoured in high-competition environments.

Efficacy of endoscopic retrograde cholangiopancreatography in familial adenomatous polyposis patients after duodenectomy.

Objectives: Familial adenomatous polyposis (FAP) patients with Spigelman stage IV polyposis should be considered for prophylactic duodenectomy. Post-surgical pancreaticobiliary complications occur and may require management via endoscopic retrograde cholangiopancreatography (ERCP). We aimed to assess the success and adverse events of ERCP in FAP patients after pancreas-sparing duodenectomy (PSD) and pancreaticoduodenectomy (PD). Methods: A retrospective review of FAP patients who underwent ERCP after PSD or PD from 1992 to 2020 at a quaternary referral center was completed. The technical success of ERCP was defined as the ability to identify the anastomosis and cannulate the duct. Post-procedural adverse events were defined by bleeding, perforation, pancreatitis, or cholangitis. Clinical outcomes included the need for surgical intervention and recurrent pancreatitis after ERCP were assessed. Results: Of 84 FAP patients with duodenectomy, 12 patients with PSD and two patients with PD underwent 17 ERCPs for pancreatic indications and five for biliary indications. The technical success of ERCP in patients with PSD and a single neoampullary complex for pancreatic (n = 6) and biliary (n = 5) indications was 100% but for those with PD (n = 2) or PSD reconstruction with pancreatic divisum or separate anastomoses (n = 3), it was 0%. Surgical intervention was required in 50% of patients with technically failed ERCP after PSD (2/4) and PD (1/2). There were no adverse events. Conclusions: ERCP is expected to be therapeutically successful for biliary complications following PSD. Assessment and potential therapy for pancreatitis post-PSD are best in the setting of a single neo-ampullary complex rather than in PD or PSD with pancreatic divisum.

Transgenerational plasticity in the eye size of Daphnia.

It is well established that environmental signals can induce phenotypic responses that persist for multiple generations. The induction of such 'transgenerational plasticity' (TGP) depends upon the ability of organisms to accurately receive and process information from environmental signals. Thus, sensory systems are likely intertwined with TGP. Here we tested the link between an environmental stressor and transgenerational responses in a component of the sensory system (eye size) that is linked to enhanced vision and ecologically relevant behaviours. We reared 45 clones of Daphnia pulicaria in the presence and absence of a low-quality resource (cyanobacteria) and evaluated shifts in relative eye size in offspring. Our results revealed divergent shifts in relative eye size within- and across-generations. Parental Daphnia that were fed cyanobacteria produced a smaller eye than Daphnia fed high-quality algae. Such differences were then reversed in the offspring generation; Daphnia whose mothers were fed cyanobacteria produced larger eyes than Daphnia that were continually fed green algae. We discuss the extent to which this maternal effect on eye size is an adaptive response linked to improved foraging.

Coordinated evolution of brain size, structure, and eye size in Trinidadian killifish.

Brain size, brain architecture, and eye size vary extensively in vertebrates. However, the extent to which the evolution of these components is intricately connected remains unclear. Trinidadian killifish, Anablepsoides hartii, are found in sites that differ in the presence and absence of large predatory fish. Decreased rates of predation are associated with evolutionary shifts in brain size; males from sites without predators have evolved a relatively larger brain and eye size than males from sites with predators. Here, we evaluated the extent to which the evolution of brain size, brain structure, and eye size covary in male killifish. We utilized wild-caught and common garden-reared specimens to determine whether specific components of the brain have evolved in response to differences in predation and to determine if there is covariation between the evolution of brain size, brain structure, and eye size. We observed consistent shifts in brain architecture in second generation common garden reared, but not wild caught preserved fish. Male killifish from sites that lack predators exhibited a significantly larger telencephalon, optic tectum, cerebellum, and dorsal medulla when compared with fish from sites with predators. We also found positive connections between the evolution of brain structure and eye size but not between overall brain size and eye size. These results provide evidence for evolutionary covariation between the components of the brain and eye size. Such results suggest that selection, directly or indirectly, acts upon specific regions of the brain, rather than overall brain size, to enhance visual capabilities.

Ancestral genetic variation in phenotypic plasticity underlies rapid evolutionary changes in resurrected populations of waterfleas.

The role of phenotypic plasticity in adaptive evolution has been debated for decades. This is because the strength of natural selection is dependent on the direction and magnitude of phenotypic responses to environmental signals. Therefore, the connection between plasticity and adaptation will depend on the patterns of plasticity harbored by ancestral populations before a change in the environment. Yet few studies have directly assessed ancestral variation in plasticity and tracked phenotypic changes over time. Here we resurrected historic propagules of Daphnia spanning multiple species and lakes in Wisconsin following the invasion and proliferation of a novel predator (spiny waterflea, Bythotrephes longimanus). This approach revealed extensive genetic variation in predator-induced plasticity in ancestral populations of Daphnia It is unlikely that the standing patterns of plasticity shielded Daphnia from selection to permit long-term coexistence with a novel predator. Instead, this variation in plasticity provided the raw materials for Bythotrephes-mediated selection to drive rapid shifts in Daphnia behavior and life history. Surprisingly, there was little evidence for the evolution of trait plasticity as genetic variation in plasticity was maintained in the face of a novel predator. Such results provide insight into the link between plasticity and adaptation and highlight the importance of quantifying genetic variation in plasticity when evaluating the drivers of evolutionary change in the wild.

Endoscopic Surveillance of Duodenal Polyposis After Total Gastrectomy in Familial Adenomatous Polyposis.

The lifetime incidence of duodenal polyposis in familial adenomatous polyposis (FAP) approaches 100%, and duodenal cancer is the most common malignancy once colectomy is performed. The incidence of gastric cancer is increasing in patients with FAP, and when gastric polyps with high-grade dysplasia or cancer are present, a total gastrectomy with Roux-en-Y esophagojejunostomy is indicated. The altered anatomy after surgery and presence of adhesions from a previous colectomy make endoscopic surveillance of the duodenum with standard equipment difficult. This case report highlights an approach to duodenal polyposis surveillance in FAP after total gastrectomy with Roux-en-Y esophagojejunostomy.

Predation drives the evolution of brain cell proliferation and brain allometry in male Trinidadian killifish, Rivulus hartii.

The external environment influences brain cell proliferation, and this might contribute to brain plasticity underlying adaptive behavioural changes. Additionally, internal genetic factors influence the brain cell proliferation rate. However, to date, researchers have not examined the importance of environmental versus genetic factors in causing natural variation in brain cell proliferation. Here, we examine brain cell proliferation and brain growth trajectories in free-living populations of Trinidadian killifish, Rivulus hartii, exposed to contrasting predation environments. Compared to populations without predators, populations in high predation (HP) environments exhibited higher rates of brain cell proliferation and a steeper brain growth trajectory (relative to body size). To test whether these differences in the wild persist in a common garden environment, we reared first-generation fish originating from both predation environments in uniform laboratory conditions. Just as in the wild, brain cell proliferation and brain growth in the common garden were greater in HP populations than in no predation populations. The differences in cell proliferation observed across the brain in both the field and common garden studies indicate that the differences are probably genetically based and are mediated by evolutionary shifts in overall brain growth and life-history traits.

The evolution of eye size in response to increased fish predation in Daphnia.

Variation in eye size is ubiquitous across taxa. Increased eye size is correlated with improved vision and increased fitness via shifts in behavior. Tests of the drivers of eye size evolution have focused on macroevolutionary studies evaluating the importance of light availability. Predator-induced mortality has recently been identified as a potential driver of eye size variation. Here, we tested the influence of increased predation by the fish predator, the alewife (Alosa pseudoharengus) on eye size evolution in waterfleas (Daphnia ambigua) from lakes in Connecticut. We quantified the relative eye size of Daphnia from lakes with and without alewife using wild-caught and third-generation laboratory reared specimens. This includes comparisons between lakes where alewife are present seasonally (anadromous) or permanently (landlocked). Wild-caught specimens did not differ in eye size across all lakes. However, third-generation lab reared Daphnia from lakes with alewife, irrespective of the form of alewife predation, exhibited significantly larger eyes than Daphnia from lakes without alewife. This genetically based increase in eye size may enhance the ability of Daphnia to detect predators. Alternatively, such shifts in eye size may be an indirect response to Daphnia aggregating at the bottom of lakes. To test these mechanisms, we collected Daphnia as a function of depth and found that eye size differed in Daphnia found at the surface versus the bottom of the water column between anadromous alewife and no alewife lakes. However, we found no evidence of Daphnia aggregating at the bottom of lakes. Such results indicate that the evolution of a larger eye may be explained by a connection between eyes and enhanced survival. We discuss the cause of the lack of concordance in eye size variation between our phenotypic and genetic specimens and the ultimate drivers of eye size.

Novel ecological and climatic conditions drive rapid adaptation in invasive Florida Burmese pythons.

Invasive species provide powerful in situ experimental systems for studying evolution in response to selective pressures in novel habitats. While research has shown that phenotypic evolution can occur rapidly in nature, few examples exist of genomewide adaptation on short "ecological" timescales. Burmese pythons (Python molurus bivittatus) have become a successful and impactful invasive species in Florida over the last 30 years despite major freeze events that caused high python mortality. We sampled Florida Burmese pythons before and after a major freeze event in 2010 and found evidence for directional selection in genomic regions enriched for genes associated with thermosensation, behaviour and physiology. Several of these genes are linked to regenerative organ growth, an adaptive response that modulates organ size and function with feeding and fasting in pythons. Independent histological and functional genomic data sets provide additional layers of support for a contemporary shift in invasive Burmese python physiology. In the Florida population, a shift towards maintaining an active digestive system may be driven by the fitness benefits of maintaining higher metabolic rates and body temperature during freeze events. Our results suggest that a synergistic interaction between ecological and climatic selection pressures has driven adaptation in Florida Burmese pythons, demonstrating the often-overlooked potential of rapid adaptation to influence the success of invasive species.

Rapid evolution mitigates the ecological consequences of an invasive species (Bythotrephes longimanus) in lakes in Wisconsin.

Invasive species have extensive negative consequences for biodiversity and ecosystem health. Novel species also drive contemporary evolution in many native populations, which could mitigate or amplify their impacts on ecosystems. The predatory zooplankton Bythotrephes longimanus invaded lakes in Wisconsin, USA, in 2009. This invasion caused precipitous declines in zooplankton prey (Daphnia pulicaria), with cascading impacts on ecosystem services (water clarity). Here, we tested the link between Bythotrephes invasion, evolution in Daphnia and post-invasion ecological dynamics using 15 years of long-term data in conjunction with comparative experiments. Invasion by Bythotrephes is associated with rapid increases in the body size of Daphnia Laboratory experiments revealed that such shifts have a genetic component; third-generation laboratory-reared Daphnia from 'invaded' lakes are significantly larger and exhibit greater reproductive effort than individuals from 'uninvaded' lakes. This trajectory of evolution should accelerate Daphnia population growth and enhance population persistence. We tested this prediction by comparing analyses of long-term data with laboratory-based simulations, and show that rapid evolution in Daphnia is associated with increased population growth in invaded lakes.

Contrasting gene expression programs correspond with predator-induced phenotypic plasticity within and across generations in Daphnia.

Research has shown that a change in environmental conditions can alter the expression of traits during development (i.e., "within-generation phenotypic plasticity") as well as induce heritable phenotypic responses that persist for multiple generations (i.e., "transgenerational plasticity", TGP). It has long been assumed that shifts in gene expression are tightly linked to observed trait responses at the phenotypic level. Yet, the manner in which organisms couple within- and TGP at the molecular level is unclear. Here we tested the influence of fish predator chemical cues on patterns of gene expression within- and across generations using a clone of Daphnia ambigua that is known to exhibit strong TGP but weak within-generation plasticity. Daphnia were reared in the presence of predator cues in generation 1, and shifts in gene expression were tracked across two additional asexual experimental generations that lacked exposure to predator cues. Initial exposure to predator cues in generation 1 was linked to ~50 responsive genes, but such shifts were 3-4× larger in later generations. Differentially expressed genes included those involved in reproduction, exoskeleton structure and digestion; major shifts in expression of genes encoding ribosomal proteins were also identified. Furthermore, shifts within the first-generation and transgenerational shifts in gene expression were largely distinct in terms of the genes that were differentially expressed. Such results argue that the gene expression programmes involved in within- vs. transgeneration plasticity are fundamentally different. Our study provides new key insights into the plasticity of gene expression and how it relates to phenotypic plasticity in nature.

The evolution of vertebrate eye size across an environmental gradient: phenotype does not predict genotype in a Trinidadian killifish.

Vertebrates exhibit substantial variation in eye size. Eye size correlates positively with visual capacity and behaviors that enhance fitness, such as predator avoidance. This foreshadows a connection between predation and eye size evolution. Yet, the conditions that favor evolutionary shifts in eye size, besides the well-known role for light availability, are unclear. We tested the influence of predation on the evolution of eye size in Trinidadian killifish, Rivulus hartii. Rivulus are located across a series of communities where they coexist with visually oriented piscivores ("high predation" sites), and no predators ("Rivulus-only" sites). Wild-caught Rivulus from high predation sites generally exhibited a smaller relative eye size than communities that lack predators. Yet, such differences were inconsistent across rivers. Second-generation common garden reared fish revealed repeatable decreases in eye size in Rivulus from high predation sites. We performed additional experiments that tested the importance of light and resources on eye size evolution. Sites that differ in light or resource availability did not differ in eye size. Our results argue that differences in predator-induced mortality underlie genetically-based shifts in vertebrate eye size. We discuss the drivers of eye size evolution in light of the nonparallel trends between the phenotypic and common garden results.

Increased juvenile predation is not associated with evolved differences in adult brain size in Trinidadian killifish (Rivulus hartii).

Vertebrates exhibit extensive variation in brain size. The long-standing assumption is that this variation is driven by ecologically mediated selection. Recent work has shown that an increase in predator-induced mortality is associated with evolved increases and decreases in brain size. Thus, the manner in which predators induce shifts in brain size remains unclear. Increased predation early in life is a key driver of many adult traits, including life-history and behavioral traits. Such results foreshadow a connection between age-specific mortality and selection on adult brain size. Trinidadian killifish, Rivulus hartii, are found in sites with and without guppies, Poecilia reticulata. The densities of Rivulus drop dramatically in sites with guppies because guppies prey upon juvenile Rivulus. Previous work has shown that guppy predation is associated with the evolution of adult life-history traits in Rivulus. In this study, we compared second-generation laboratory-born Rivulus from sites with and without guppies for differences in brain size and associated trade-offs between brain size and other components of fitness. Despite the large amount of existing research on the importance of early-life events on the evolution of adult traits, and the role of predation on both behavior and brain size, we did not find an association between the presence of guppies and evolutionary shifts in Rivulus brain size. Such results argue that increased rates of juvenile mortality may not alter selection on adult brain size.

Predator-driven brain size evolution in natural populations of Trinidadian killifish (Rivulus hartii).

Vertebrates exhibit extensive variation in relative brain size. It has long been assumed that this variation is the product of ecologically driven natural selection. Yet, despite more than 100 years of research, the ecological conditions that select for changes in brain size are unclear. Recent laboratory selection experiments showed that selection for larger brains is associated with increased survival in risky environments. Such results lead to the prediction that increased predation should favour increased brain size. Work on natural populations, however, foreshadows the opposite trajectory of evolution; increased predation favours increased boldness, slower learning, and may thereby select for a smaller brain. We tested the influence of predator-induced mortality on brain size evolution by quantifying brain size variation in a Trinidadian killifish, Rivulus hartii, from communities that differ in predation intensity. We observed strong genetic differences in male (but not female) brain size between fish communities; second generation laboratory-reared males from sites with predators exhibited smaller brains than Rivulus from sites in which they are the only fish present. Such trends oppose the results of recent laboratory selection experiments and are not explained by trade-offs with other components of fitness. Our results suggest that increased male brain size is favoured in less risky environments because of the fitness benefits associated with faster rates of learning and problem-solving behaviour.

Effects of ensembles on methane hydrate nucleation kinetics.

By performing molecular dynamics simulations to form a hydrate with a methane nano-bubble in liquid water at 250 K and 50 MPa, we report how different ensembles, such as the NPT, NVT, and NVE ensembles, affect the nucleation kinetics of the methane hydrate. The nucleation trajectories are monitored using the face-saturated incomplete cage analysis (FSICA) and the mutually coordinated guest (MCG) order parameter (OP). The nucleation rate and the critical nucleus are obtained using the mean first-passage time (MFPT) method based on the FS cages and the MCG-1 OPs, respectively. The fitting results of MFPT show that hydrate nucleation and growth are coupled together, consistent with the cage adsorption hypothesis which emphasizes that the cage adsorption of methane is a mechanism for both hydrate nucleation and growth. For the three different ensembles, the hydrate nucleation rate is quantitatively ordered as follows: NPT > NVT > NVE, while the sequence of hydrate crystallinity is exactly reversed. However, the largest size of the critical nucleus appears in the NVT ensemble, rather than in the NVE ensemble. These results are helpful for choosing a suitable ensemble when to study hydrate formation via computer simulations, and emphasize the importance of the order degree of the critical nucleus.

Absence of a Periampullary Mass on Cross-sectional Imaging Delays Diagnosis and Time to Pancreatoduodenectomy But Does Not Impair Outcome.

BACKGROUND: The aim of this study was to assess whether the lack of a radiological mass in patients with periampullary malignancies led to protracted diagnosis, delayed resection, and an inferior outcome. METHODS: The departmental database was interrogated to identify all patients undergoing pancreatoduodenectomy during the period 2000-2014. The absence of a mass on cross-sectional and endoscopic ultrasound was noted. The interval between imaging and surgery was evaluated and related to the absence of a mass. The relationship between mass/no mass and the pathological profile was also assessed. RESULTS: Among 490 patients who underwent pancreatoduodenectomy for periampullary malignancies, masses were detected in 299 patients. Patients with undetected mass on either endoscopic ultrasonography (EUS) or computed tomography (CT)/magnetic resonance imaging (MRI) had a longer median interval from initial imaging to resection than detected mass with no difference in survival (66 vs. 41 days, p = 0.001). The absence of a mass was more common in cholangiocarcinomas (p < 0.001). The absence of a mass on imaging was associated with smaller size on final histopathology (2.4 vs. 2.8 cm; p < 0.001). CONCLUSIONS: The absence of a mass with all modalities in patients with a periampullary malignancy leads to a delayed diagnosis without a significant effect on survival.