Surface temperatures are influenced by handling stress independently of corticosterone levels in wild king penguins (Aptenodytes patagonicus).

Assessing the physiological stress responses of wild animals opens a window for understanding how organisms cope with environmental challenges. Since stress response is associated with changes in body temperature, the use of body surface temperature through thermal imaging could help to measure acute and chronic stress responses non-invasively. We used thermal imaging, acute handling-stress protocol and an experimental manipulation of corticosterone (the main glucocorticoid hormone in birds) levels in breeding king penguins (Aptenodytes patagonicus), to assess: 1. The potential contribution of the Hypothalamo-Pituitary-Adrenal (HPA) axis in mediating chronic and acute stress-induced changes in adult surface temperature, 2. The influence of HPA axis manipulation on parental investment through thermal imaging of eggs and brooded chicks, and 3. The impact of parental treatment on offspring thermal's response to acute handling. Maximum eye temperature (Teye) increased and minimum beak temperature (Tbeak) decreased in response to handling stress in adults, but neither basal nor stress-induced surface temperatures were significantly affected by corticosterone implant. While egg temperature was not significantly influenced by parental treatment, we found a surprising pattern for chicks: chicks brooded by the (non-implanted) partner of corticosterone-implanted individuals exhibited higher surface temperature (both Teye and Tbeak) than those brooded by glucocorticoid-implanted or control parents. Chick's response to handling in terms of surface temperature was characterized by a drop in both Teye and Tbeak independently of parental treatment. We conclude that the HPA axis seems unlikely to play a major role in determining chronic or acute changes in surface temperature in king penguins. Changes in surface temperature may primarily be mediated by the Sympathetic-Adrenal-Medullary (SAM) axis in response to stressful situations. Our experiment did not reveal a direct impact of parental HPA axis manipulation on parental investment (egg or chick temperature), but a potential influence on the partner's brooding behaviour.

How to solve novel problems: the role of associative learning in problem-solving performance in wild great tits Parus major.

Although problem-solving tasks are frequently used to assess innovative ability, the extent to which problem-solving performance reflects variation in cognitive skills has been rarely formally investigated. Using wild breeding great tits facing a new non-food motivated problem-solving task, we investigated the role of associative learning in finding the solution, compared to multiple other non-cognitive factors. We first examined the role of accuracy (the proportion of contacts made with the opening part of a string-pulling task), neophobia, exploration, activity, age, sex, body condition and participation time on the ability to solve the task. To highlight the effect of associative learning, we then compared accuracy between solvers and non-solvers, before and after the first cue to the solution (i.e., the first time they pulled the string opening the door). We finally compared accuracy over consecutive entrances for solvers. Using 884 observations from 788 great tits tested from 2010 to 2015, we showed that, prior to initial successful entrance, solvers were more accurate and more explorative than non-solvers, and that females were more likely to solve the task than males. The accuracy of solvers, but not of non-solvers, increased significantly after they had the opportunity to associate string pulling with the movement of the door, giving them a first cue to the task solution. The accuracy of solvers also increased over successive entrances. Our results demonstrate that variations in problem-solving performance primarily reflect inherent individual differences in associative learning, and are also to a lesser extent shaped by sex and exploratory behaviour.

Shrinking Alpine chamois: higher spring temperatures over the last 27 years in Switzerland are linked to a 3 kg reduction in body mass of yearlings.

Although climate change is considered to be partly responsible for the size change observed in numerous species, the relevance of this hypothesis for ungulates remains debated. We used body mass measurements of 5635 yearlings (i.e. 1.5 years old) of Alpine chamois (Rupicapra rupicapra) harvested in September in the Swiss Alps (Ticino canton) from 1992 to 2018. In our study area, during this period, yearlings shrank by ca 3 kg while temperatures between May and July rose by 1.7°C. We identified that warmer temperatures during birth and the early suckling period (9 May to 2 July in the year of birth) had the strongest impact on yearling mass. Further analyses of year-detrended mass and temperature data indicate that this result was not simply due to changes in both variables over years, but that increases in temperature during this particularly sensitive time window for development and growth are responsible for the decrease in body mass of yearling chamois. Altogether, our results suggest that rising temperatures in the Alpine regions could significantly affect the ecology and evolution of this wild ungulate.

Adult body mass is heritable, positively genetically correlated and under selection of differing shapes between the sexes in a bird with little apparent sexual dimorphism.

In most animals, body mass varies with ecological conditions and is expected to reflect how much energy can be allocated to reproduction and survival. Because the sexes often differ in their resource acquisition and allocation strategies, variations in adult body mass and their consequences on fitness can differ between the sexes. Assessing the relative contributions of environmental and genetic effects (i.e. heritability)-and whether these effects and their fitness consequences are sex-specific-is essential to gain insights into the evolution of sexual dimorphism and sexual conflicts. We used 20+ years of data to study the sources of variation in adult body mass and associated fitness consequences in a bird with biparental care, the Alpine swift (Tachymarptis melba). Swifts appear monomorphic to human observers, though subtle dimorphisms are present. We first investigated the effects of weather conditions on adult body mass using a sliding window analysis approach. We report a positive effect of temperature and a negative effect of rainfall on adult body mass, as expected for an aerial insectivorous bird. We then quantified the additive genetic variance and heritability of body mass in both sexes and assessed the importance of genetic constraints on mass evolution by estimating the cross-sex genetic correlation. Heritability was different from zero in both sexes at ~0.30. The positive cross-sex genetic correlation and comparable additive genetic variance between the sexes suggest the possibility for evolutionary constraints when it comes to body mass. Finally, we assessed the sex-specific selection on adjusted body mass using multiple fitness components. We report directional positive and negative selection trending towards stabilizing and diversifying selection on females and males respectively in relation to the weighted proportion of surviving fledglings. Overall, these results suggest that while body mass may be able to respond to environmental conditions and evolve, genetic constraints would result in similar changes in both sexes or an overall absence of response to selection. It remains unclear whether the weak (1%) dimorphism in Alpine swift body mass we report is simply a result of the similar fitness peaks between the sexes or of genetic constraints.

Disentangling the "many-eyes", "dilution effect", "selfish herd", and "distracted prey" hypotheses in shaping alert and flight initiation distance in a colonial seabird.

Group living is thought to have important antipredator benefits for animals, owing to the mechanisms of shared vigilance ("many-eyes" hypothesis), risk dilution ("dilution effect" hypothesis), and relative safety in the center of the group ("selfish herd" hypothesis). However, it can also incur costs since social stimuli, such as conspecific aggression, may distract individuals from anti-predator behavior ("distracted prey" hypothesis). We simultaneously evaluated how these four different hypotheses shape anti-predator behaviors of breeding king penguins (Aptenodytes patagonicus), which aggregate into large colonies, experience frequent aggressive social interactions, and are regularly exposed to predation by giant petrels (Macronectes sp.) and brown skuas (Catharacta loonbergi) when breeding on land. We approached 200 incubating penguins at four different periods of the breeding season across a range of overall increasing colony densities. We measured the distance at which focal birds detected the approaching threat (alert distance: AD), whether birds decided to flee or not, and the distance of flight initiation (flight initiation distance: FID, viz. the bird attempting to walk away with its egg on its feet). We quantified relative local neighbor density, centrality within the colony (rank), and the number of aggressions the focal bird emitted towards neighbors during the approach. We found that birds engaged in aggressive conflicts with neighbors were less likely to flee, and that increasing relative local neighbor density at low and medium overall colony density resulted in a decrease in bird AD, both supporting the "distracted prey" hypothesis. However, at maximal overall colony density, increasing relative local neighbor density resulted in longer AD, supporting the "many-eyes" hypothesis. We found no support for the "dilution effect" and "selfish herd" hypotheses, and no effects of any hypothesis on FID.

The effect of climate change on avian offspring production: A global meta-analysis.

Climate change affects timing of reproduction in many bird species, but few studies have investigated its influence on annual reproductive output. Here, we assess changes in the annual production of young by female breeders in 201 populations of 104 bird species (N = 745,962 clutches) covering all continents between 1970 and 2019. Overall, average offspring production has declined in recent decades, but considerable differences were found among species and populations. A total of 56.7% of populations showed a declining trend in offspring production (significant in 17.4%), whereas 43.3% exhibited an increase (significant in 10.4%). The results show that climatic changes affect offspring production through compounded effects on ecological and life history traits of species. Migratory and larger-bodied species experienced reduced offspring production with increasing temperatures during the chick-rearing period, whereas smaller-bodied, sedentary species tended to produce more offspring. Likewise, multi-brooded species showed increased breeding success with increasing temperatures, whereas rising temperatures were unrelated to reproductive success in single-brooded species. Our study suggests that rapid declines in size of bird populations reported by many studies from different parts of the world are driven only to a small degree by changes in the production of young.

Molecular investigation on infection by haemosporidians in three Western Palearctic species of swift (Apodidae) and their ectoparasitic louse flies.

Swifts (Apodidae) are an unusual group of birds that spend most of their lives in flight, landing only when breeding. Although this aerial lifestyle greatly reduces their likelihood of being bitten by vectors and infected by vector-born parasites, swifts can still be heavily infested during breeding by nest-based vectors such as louse flies (Hippoboscidae). Here, we investigated host, vector, and vector-borne parasite relationships in the three most widespread swift species in the Western Palearctic (WP): common swifts (Apus apus), pallid swifts (A. pallidus), and alpine swifts (Tachymarptis melba), their nest-based louse flies (Crataerina pallida and C. melbae) and avian haemosporidians (genera Haemoproteus, Plasmodium, and Leucocytozoon). Studies of haemosporidian infections in Apodidae remain limited, with clear evidence of infection found to date in just four Neotropical and one Australasian species. The possible role of louse flies in transmitting haemosporidian infections has never been tested in swifts. We assessed the occurrence of haemosporidian infection by PCR screenings of DNA from blood samples from 34 common swifts and 44 pallid swifts from Italy, and 45 alpine swifts from Switzerland. We also screened 20 ectoparasitic louse flies present on 20 birds and identified them by both morphological features and cytochrome oxidase subunit 1 (COI) barcodes. Our results provide no evidence of haemosporidian infection in the 123 swifts tested or in the two louse fly species we identified. Our findings are consistent with available knowledge showing no haemosporidian occurrence in WP swift species and that the most likely infection route for these highly aerial species (via louse fly ectoparasites during nesting) is unlikely.

Solving the conundrum of intra-specific variation in metabolic rate: A multidisciplinary conceptual and methodological toolkit: New technical developments are opening the door to an understanding of why metabolic rate varies among individual animals of a species: New technical developments are opening the door to an understanding of why metabolic rate varies among individual animals of a species.

Researchers from diverse disciplines, including organismal and cellular physiology, sports science, human nutrition, evolution and ecology, have sought to understand the causes and consequences of the surprising variation in metabolic rate found among and within individual animals of the same species. Research in this area has been hampered by differences in approach, terminology and methodology, and the context in which measurements are made. Recent advances provide important opportunities to identify and address the key questions in the field. By bringing together researchers from different areas of biology and biomedicine, we describe and evaluate these developments and the insights they could yield, highlighting the need for more standardisation across disciplines. We conclude with a list of important questions that can now be addressed by developing a common conceptual and methodological toolkit for studies on metabolic variation in animals.

Post-mortem changes of the vascular system-a thanatological study using multidetector computed tomography.

Forensic pathologists have to deal with post-mortem changes of the human body. Those post-mortem phenomena are familiar and largely described in thanatology. However, knowledge about the influence of post-mortem phenomena on the vascular system is more limited, except for the apparition and development of cadaveric lividity. The introduction of multidetector computed tomography (MDCT) and magnetic resonance imaging (MRI) in the forensic field and the expansion of their usage in medico-legal routine, allow for exploring the inside of corpses differently and may play a part in the understanding of thanatological processes. This study aimed to describe post-mortem changes in the vascular system by investigating the presence of gas and collapsed vessels.We investigated post-mortem MDCT data of 118 human bodies. Cases with internal/external bleeding or corporal lesion allowing contamination with external air were excluded. Major vessels and heart cavities were systematically explored and a trained radiologist semi-quantitatively assessed the presence of gas.Collapsed veins were observed in 61.9% of cases (CI95% 52.5 to 70.6) and arteries in 33.1% (CI95% 24.7 to 42.3). Vessels most often affected were for arteries: common iliac (16.1%), abdominal aorta (15.3%), external iliac (13.6%), and for veins: infra-renal vena cava (45.8%), common iliac (22.0%), renal (16.9%), external iliac (16.1%), and supra-renal vena cava (13.6%). Cerebral arteries and veins, coronary arteries, and subclavian vein were unaffected. The presence of collapsed vessels was associated with a minor degree of cadaveric alteration. We observed that arteries and veins follow the same pattern of gas apparition for both the quantity and the location.In post-mortem radiology, collapsed vessels and intravascular gas are frequently visualized and as a result of all post-mortem changes, the assessment of the distribution of blood can be confusing. Therefore, knowledge of thanatological phenomena is crucial to prevent post-mortem radiological misapprehensions and possible false diagnoses.

Effects of the social environment on vertebrate fitness and health in nature: Moving beyond the stress axis.

Social interactions are a ubiquitous feature of the lives of vertebrate species. These may be cooperative or competitive, and shape the dynamics of social systems, with profound effects on individual behavior, physiology, fitness, and health. On one hand, a wealth of studies on humans, laboratory animal models, and captive species have focused on understanding the relationships between social interactions and individual health within the context of disease and pathology. On the other, ecological studies are attempting an understanding of how social interactions shape individual phenotypes in the wild, and the consequences this entails in terms of adaptation. Whereas numerous studies in wild vertebrates have focused on the relationships between social environments and the stress axis, much remains to be done in understanding how socially-related activation of the stress axis coordinates other key physiological functions related to health. Here, we review the state of our current knowledge on the effects that social interactions may have on other markers of vertebrate fitness and health. Building upon complementary findings from the biomedical and ecological fields, we identify 6 key physiological functions (cellular metabolism, oxidative stress, cellular senescence, immunity, brain function, and the regulation of biological rhythms) which are intimately related to the stress axis, and likely directly affected by social interactions. Our goal is a holistic understanding of how social environments affect vertebrate fitness and health in the wild. Whereas both social interactions and social environments are recognized as important sources of phenotypic variation, their consequences on vertebrate fitness, and the adaptive nature of social-stress-induced phenotypes, remain unclear. Social flexibility, or the ability of an animal to change its social behavior with resulting changes in social systems in response to fluctuating environments, has emerged as a critical underlying factor that may buffer the beneficial and detrimental effects of social environments on vertebrate fitness and health.

Variation in feather corticosterone levels in Alpine swift nestlings provides support for the hypo-responsive hypothesis.

In birds, feather corticosterone values (CORTf) are increasingly used as a retrospective and integrative proxy of an individual's physiological state during the period of feather growth. Relatively high CORTf values are usually interpreted as an indicator of exposure to energy-demanding or stressful conditions during feather growth. However, in nestlings this interpretation might not always hold true. The reasons are that, firstly nestlings (especially altricial ones) still develop their hypothalamo-pituitary-adrenal (HPA) reactivity during the growth of their feathers. Hence, at a young age, nestlings might be unable to mount a substantial adrenocortical stress response. Secondly, some species are able to down-regulate their metabolism during food scarcity and therewith probably also their CORT release. Consequently, CORTf values may not unambiguously reflect whether nestlings have suffered from energy-demanding or stress situations. Relatively high CORTf values might indicate either energy-demanding or stressful conditions ('stress responsive hypothesis'), or - conversely - favourable conditions during the period of feather growth ('hypo-responsive hypothesis'). In the altricial Alpine swift (Tachymarptis melba), we tested which factors help to distinguish between the two hypotheses by considering factors which affect CORT release (brood size, weather) and factors which are affected by high CORT levels (nestling size and condition). We measured CORTf in 205 nestlings over 7 years and collected data on brood size, body size, body condition and prevailing weather. Nestling CORTf values were positively correlated with body condition and negatively with adverse weather, supporting the hypo-responsive hypothesis. Results from the Alpine swift study, supplemented with a survey of the literature, show that relatively easily collected parameters on brood size, nestling size and condition, and environmental factors can help to distinguish between the two hypotheses. A meaningful interpretation of nestling CORTf should only be made in the context of species-specific traits.

Bigger is not always better: Viability selection on body mass varies across life stages in a hibernating mammal.

Body mass is often viewed as a proxy of past access to resources and of future survival and reproductive success. Links between body mass and survival or reproduction are, however, likely to differ between age classes and sexes. Remarkably, this is rarely taken into account in selection analyses. Selection on body mass is likely to be the primary target accounting for juvenile survival until reproduction but may weaken after recruitment. Males and females also often differ in how they use resources for reproduction and survival. Using a long-term study on body mass and annual survival in yellow-bellied marmots (Marmota flaviventer), we show that body mass was under stabilizing viability selection in the first years of life, before recruitment, which changed to positive directional selection as age increased and animals matured. We found no evidence that viability selection across age classes on body mass differed between sexes. By investigating the link between running speed and body mass, we show that the capacity to escape predators was not consistent across age classes and followed a quadratic relationship at young ages only. Overall, our results indicate that mature age classes exhibit traditional patterns of positive viability selection on body mass, as expected in a hibernating mammal, but that mass in the first years of life is subjected to stabilizing selection which may come from additional predation pressures that negate the benefits of the largest body masses. Our study highlights the importance to disentangle selection pressures on traits across critical age (or life) classes.

Long-term intake of the illegal diet pill DNP reduces lifespan in a captive bird model.

2,4-Dinitrophenol (DNP), a molecule uncoupling mitochondrial oxidative phosphorylation from oxygen consumption, is illegally used by humans as a diet pill, but is nonetheless investigated as a potential human medicine against 'metabesity'. Due to its proven acute toxicity and the scarceness of long-term studies on DNP administration in vertebrates, we determined the impact of a long-term DNP treatment (~4 mg.kg-1.day-1, i.e. within the range taken illegally by humans) on body mass, metabolism, ageing and lifespan in a captive bird model, the zebra finch. The chronic absorption of DNP over life (>4 years) led to a mild increase in energy expenditure (ca. +11% compared to control group), without significantly altering the normal slight increase in body mass with age. DNP did not significantly influence the alteration of physical performance, the rise in oxidative damage, or the progressive shortening of telomeres with age. However, DNP-treated individuals had a significantly shorter lifespan (ca. -21% in median lifespan compared to control group), thereby raising potential concerns about DNP use as a diet pill or medicine.

Image-guided percutaneous cryoablation of unresectable sacrococcygeal chordoma: Feasibility and outcome in a selected group of patients with long term follow-up.

BACKGROUND: Chordoma is a rare malignant tumor of the axial skeleton. Percutaneous cryoablation (PCA) is a minimally invasive technique that allows freezing of tumors under imaging control. The purpose of our retrospective study was to investigate the outcome of PCA in a selected cohort of patients with sacrococcygeal chordoma, with a minimum of 5 years follow-up. MATERIALS AND METHODS: Four patients were treated in 10 sessions. The mean follow-up was 57.3 months. We evaluated the feasibility, the procedure-related complications, the impact on pain control and oncological outcomes. RESULTS: Freezing of 100% of the tumor volume was possible in 60%. Pain control was not reliably evaluable. Local recurrence occurred in 90% of the treated lesions; the mean time to progression was 8.1 months (range 1.5-16). At last follow-up, one patient had died of the disease, one of another cause and one was receiving the best supportive care. The only patient alive without the disease had received additional carbon-ion radiotherapy. The 5-year survival rate after index PCA was 50%. CONCLUSION: Complete freezing of the tumor was technically challenging, mainly due to the complex local anatomy. Recurrence occurred in 90% of the lesions treated. PCA should be considered with caution in the curative management of sacrococcygeal chordoma.

Fluctuating optimum and temporally variable selection on breeding date in birds and mammals.

Temporal variation in natural selection is predicted to strongly impact the evolution and demography of natural populations, with consequences for the rate of adaptation, evolution of plasticity, and extinction risk. Most of the theory underlying these predictions assumes a moving optimum phenotype, with predictions expressed in terms of the temporal variance and autocorrelation of this optimum. However, empirical studies seldom estimate patterns of fluctuations of an optimum phenotype, precluding further progress in connecting theory with observations. To bridge this gap, we assess the evidence for temporal variation in selection on breeding date by modeling a fitness function with a fluctuating optimum, across 39 populations of 21 wild animals, one of the largest compilations of long-term datasets with individual measurements of trait and fitness components. We find compelling evidence for fluctuations in the fitness function, causing temporal variation in the magnitude, but not the direction of selection. However, fluctuations of the optimum phenotype need not directly translate into variation in selection gradients, because their impact can be buffered by partial tracking of the optimum by the mean phenotype. Analyzing individuals that reproduce in consecutive years, we find that plastic changes track movements of the optimum phenotype across years, especially in bird species, reducing temporal variation in directional selection. This suggests that phenological plasticity has evolved to cope with fluctuations in the optimum, despite their currently modest contribution to variation in selection.

Born to be young? Prenatal thyroid hormones increase early-life telomere length in wild collared flycatchers.

The underlying mechanisms of the lifelong consequences of prenatal environmental condition on health and ageing remain little understood. Thyroid hormones (THs) are important regulators of embryogenesis, transferred from the mother to the embryo. Since prenatal THs can accelerate early-life development, we hypothesized that this might occur at the expense of resource allocation in somatic maintenance processes, leading to premature ageing. Therefore, we investigated the consequences of prenatal TH supplementation on potential hallmarks of ageing in a free-living avian model in which we previously demonstrated that experimentally elevated prenatal TH exposure accelerates early-life growth. Using cross-sectional sampling, we first report that mitochondrial DNA (mtDNA) copy number and telomere length significantly decrease from early-life to late adulthood, thus suggesting that these two molecular markers could be hallmarks of ageing in our wild bird model. Elevated prenatal THs had no effect on mtDNA copy number but counterintuitively increased telomere length both soon after birth and at the end of the growth period (equivalent to offsetting ca 4 years of post-growth telomere shortening). These findings suggest that prenatal THs might have a role in setting the 'biological' age at birth, but raise questions about the nature of the evolutionary costs of prenatal exposure to high TH levels.

Cryoablation of Extra-Abdominal Desmoid Tumors: A Single-Center Experience with Literature Review.

Cryoablation (CA) has gained popularity in the treatment of benign and malignant musculoskeletal tumors. While extra-abdominal desmoid (EAD) tumors are not malignant, they remain challenging to treat because of their high local recurrence rate. We reviewed all EAD tumors treated with CA at our institution between November 2012 and March 2020. Fourteen procedures were performed on nine females and one male (mean age, 33 ± 18 years) as either first-line (n = 4) or salvage therapy (n = 6) with curative intent (n = 8) or tumor debulking (n = 2). Mean tumor size was 63.6 cm3 (range, 3.4-169 cm3). Contrast-enhanced MRI was performed before treatment and at 3-, 6-, and 12-month follow-up. Treatment outcome was based on the change in enhanced tumor volume (ET-V). For curatively treated patients, the mean ET-V change was -97 ± 7%, -44 ± 143%, and +103 ± 312% at 3, 6, and 12 months, respectively. For debulking patients, the mean ET-V change was -98 ± 4%, +149 ± 364%, and +192 ± 353% at 3, 6, and 12 months, respectively. During a mean follow-up of 53.7 months (range, 12-83 months), one grade III and one grade IV complication were noted. We found CA to be safe and well tolerated in patients with EAD.

Foster rather than biological parental telomere length predicts offspring survival and telomere length in king penguins.

Because telomere length and dynamics relate to individual growth, reproductive investment and survival, telomeres have emerged as possible markers of individual quality. Here, we tested the hypothesis that, in species with parental care, parental telomere length can be a marker of parental quality that predicts offspring phenotype and survival. In king penguins (Aptenodytes patagonicus), we experimentally swapped the single egg of 66 breeding pairs just after egg laying to disentangle the contribution of prelaying parental quality (e.g., genetics, investment in the egg) and/or postlaying parental quality (e.g., incubation, postnatal feeding rate) on offspring growth, telomere length and survival. Parental quality was estimated through the joint effects of biological and foster parent telomere length on offspring traits, both soon after hatching (day 10) and at the end of the prewinter growth period (day 105). We expected that offspring traits would be mostly related to the telomere lengths (i.e., quality) of biological parents at day 10 and to the telomere lengths of foster parents at day 105. Results show that chick survival up to 10 days was negatively related to biological fathers' telomere length, whereas survival up to 105 days was positively related to foster fathers' telomere lengths. Chick growth was not related to either biological or foster parents' telomere length. Chick telomere length was positively related to foster mothers' telomere length at both 10 and 105 days. Overall, our study shows that, in a species with biparental care, parents' telomere length is foremost a proxy of postlaying parental care quality, supporting the "telomere - parental quality hypothesis."

Tumor response and outcome after reverse treatment for patients with synchronous colorectal liver metastasis: a cohort study.

BACKGROUND: The reverse treatment of patients with synchronous colorectal liver metastases (CRLM) is a sequential approach with systemic chemotherapy first, followed by liver resection, and finally, primary tumor resection. The aim of this study was to assess the feasibility, the radiological and pathological tumor response to neoadjuvant therapy, recurrence rates and long-term survival after reverse treatment in a cohort study. METHODS: Data from patients with CRLM who underwent a reverse treatment from August 2008 to October 2016 were extracted from our prospective hepato-biliary database and retrospectively analyzed for response rates and survival outcomes. Radiological tumor response was assessed by RECIST (Response Evaluation Criteria In Solid Tumor) criteria and pathological response according to TRG (Tumor Regression Grade). Disease-free and overall survival were estimated with Kaplan-Meier survival curves. RESULTS: There were 44 patients with 19 rectal and 25 colonic tumors. The reverse treatment was fully completed until primary tumor resection in 41 patients (93%). Radiological assessment after chemotherapy showed 61% of complete/partial response. Pathological tumor response was major or partial in 52% of patients (TRG 1-3). Median disease-free survival after primary tumor resection was 10 months (95% CI 5-15 months). Disease-free survival at 3 and 5 years was 25% and 25%, respectively. Median overall survival was 50 months (95% CI 42-58 months). Overall survival at 3 and 5 years was 59% and 39%, respectively. CONCLUSION: The reverse treatment approach was feasible with a high rate of patients with complete treatment sequence and offers promising long-term survival for selected patients with advanced simultaneous colorectal liver metastases.