Tumor budding is an independent prognostic factor in stage III colon cancer patients: a post-hoc analysis of the IDEA-France phase III trial (PRODIGE-GERCOR).

BACKGROUND: Histological characteristics at the invasive front may reflect tumor aggressiveness; specifically, tumor budding (Bd) is an emerging prognostic biomarker in colon cancer (CC). We explored further the significance of Bd for risk stratification by evaluating survival of stage III CC patients included in the IDEA-France phase III trial. PATIENTS AND METHODS: This post-hoc study was conducted on tissue slides from 1048 stage III CC patients. Bd was scored by central review by the Bd criteria of the 2016 International Tumor Budding Consensus Conference (ITBCC 2016) and classified as Bd1 (0-4 buds/0.785 mm2), Bd2 (5-9 buds), and Bd3 (≥10 buds) categories. Disease-free survival (DFS) and overall survival (OS) were analyzed by the log-rank test. Clinicopathological features and Immunoscore® were correlated with Bd. RESULTS: Overall, Bd1, Bd2, and Bd3 were observed in 39%, 28%, and 33% of CC, respectively. Bd2 and Bd3 were associated with vascular (P = 0.002) and perineural invasions (P = 0.0009). The 3-year DFS and the 5-year OS rates for Bd (1 versus 2-3) were 79.4% versus 67.2% (P = 0.001) and 89.2% versus 80.8% (P = 0.001), respectively. This was confirmed after adjustment for relevant clinicopathological features for DFS [hazard ratio (HR) 1.41, 95% confidence interval (CI) 1.12-1.77, P = 0.003] and OS (HR 1.65, 95% CI 1.22-2.22, P = 0.001). When combined with pTN stage and Immunoscore® subgroups, Bd significantly improved disease prognostication. CONCLUSIONS: Bd demonstrated its independent prognostic value for DFS and OS. Given these findings, Bd as per the ITBCC 2016 should be mandatory in every pathology report in stage III CC patients. Bd and Immunoscore® could play a complementary role in personalized health care in this setting.

Prognostic and predictive value of the Immunoscore in stage III colon cancer patients treated with oxaliplatin in the prospective IDEA France PRODIGE-GERCOR cohort study.

BACKGROUND: The Immunoscore (IS), which prognostically classifies stage I-III colon cancer (CC) patients, was evaluated in the International Duration Evaluation of Adjuvant Therapy (IDEA) France cohort study investigating 3 versus 6 months of oxaliplatin-based adjuvant chemotherapy in stage III CC patients. PATIENTS AND METHODS: Densities of CD3+ and CD8+ T cells in the tumor and invasive margin were determined by immunohistochemistry, quantified by digital pathology, and converted to IS. Mismatch repair status was determined by immunohistochemistry or by pentaplex PCR. Prediction of disease-free survival (DFS) by IS was analyzed by a multivariable Cox regression model in each study arm. Harrell's C-statistics were used to investigate the IS performance. RESULTS: Samples of 1322 patients were available. IS Low, Intermediate (Int), and High were observed in 43.6%, 47.0%, and 9.4% of patients, respectively. IS Low identified patients at higher risk of relapse or death compared with Int + High [hazard ratio (HR) = 1.54; 95% confidence interval (CI) 1.24-1.93, P = 0.0001]. The 3-year DFS was 66.80% (95% CI 62.23-70.94) for IS Low and 77.14% (95% CI 73.50-80.35) for IS Int + High. In multivariable analysis, IS remained significantly independently associated with DFS (P = 0.003) when adjusted for sex, histological grade, T/N stage, and microsatellite instability. For mFOLFOX6-treated patients (91.6% of the cohort), a statistical significant interaction was observed for the predictive value of IS for treatment duration (3 versus 6 months) in terms of DFS (P = 0.057). IS Int + High significantly predicted benefit of 6 months of treatment (HR = 0.53; 95% CI 0.37-0.75; P = 0.0004), including clinically low- and high-risk stage III CC (all P < 0.001). Conversely, patients with IS Low (46.4%) did not significantly benefit from the 6-month mFOLFOX6 versus the 3-month mFOLFOX6. CONCLUSIONS: The prognostic value of IS for DFS was confirmed in patients with stage III CC treated with oxaliplatin-based chemotherapy. Its predictive value for DFS benefit of longer duration of mFOLFOX6 adjuvant treatment was found in IS Int + High. These results will be validated in an external independent cohort. CLINICALTRIALS. GOV REGISTRATION: NCT03422601; EudraCT Number: 2009-010384-16.

Prevalence of ankylosing spondylitis in Spain: EPISER2016 Study.

Objective: The aim of this study was to estimate the prevalence of ankylosing spondylitis (AS) in Spain.Method: This is a cross-sectional, population-based study of people aged 20 years or older in Spain. Randomly selected individuals were contacted by telephone and rheumatic disease screening was performed. If the first screening was positive, medical records were then reviewed and/or a telephone questionnaire was conducted by a rheumatologist, followed by an appointment if necessary. Cases had to fulfil the modified New York (mNY) criteria.Results: In total, 4916 individuals were included, of whom 355 had a positive screening result for AS. Of these, 11 were classified as AS. An additional individual who reported a prior diagnosis of rheumatoid arthritis had a diagnosis of AS confirmed on review of the medical records. Estimated prevalence was 0.26% (95% CI 0.14-0.49).Conclusion: EPISER2016 is the first population-based study to estimate the prevalence of AS in Spain, which has been estimated as being similar to that in other European countries.

Immunoscore and Immunoprofiling in cancer: an update from the melanoma and immunotherapy bridge 2015.

The fifth "Melanoma Bridge Meeting" took place in Naples, December 1-5th, 2015. The main topics discussed at this meeting were: Molecular and Immuno advances, Immunotherapies and Combination Therapies, Tumor Microenvironment and Biomarkers and Immunoscore. The natural history of cancer involves interactions between the tumor and the immune system of the host. The immune infiltration at the tumor site may be indicative of host response. Significant correlations were shown between the levels of immune cell infiltration in tumors and patient's clinical outcome. Moreover, incredible progress comes from the discovery of mutation-encoded tumor neoantigens. In fact, as tumors grow, they acquire mutations that are able to influence the response of patients to immune checkpoint inhibitors. It has been demonstrated that sensitivity to PD-1 and CTLA-4 blockade in patients with advanced NSCLC and melanoma was enhanced in tumors enriched for clonal neoantigens. The road ahead is still very long, but the knowledge of the mechanisms of immune escape, the study of tumor neo-antigens as well as of tumor microenvironment and the development of new immunotherapy strategies, will make cancer a more and more treatable disease.

Investigation of a leptospirosis outbreak in triathlon participants, Réunion Island, 2013.

We report herein the investigation of a leptospirosis outbreak occurring in triathlon competitors on Réunion Island, Indian Ocean. All participants were contacted by phone or email and answered a questionnaire. Detection and molecular characterization of pathogenic Leptospira was conducted in inpatients and in rodents trapped at the vicinity of the event. Of the 160 athletes competing, 101 (63·1%) agreed to participate in the study. Leptospirosis was biologically confirmed for 9/10 suspected cases either by real-time PCR or serological tests (MAT or ELISA). The total attack rate, children's attack rate, swimmers' attack rate, and the attack rate in adult swimmers were respectively estimated at 8·1% [95% confidence interval (CI) 4·3-14·7], 0%, 12·7% (95% CI 6·8-22·4) and 23·1% (95% CI 12·6-33·8). Leptospirosis cases reported significantly more wounds [risk ratio (RR) 4·5, 95% CI 1·6-13], wore complete neoprene suits less often (RR 4·3, 95% CI 1·3-14·5) and were most frequently unlicensed (RR 6·6, 95% CI 2·9-14·8). The epidemiological investigation supported that some measures such as the use of neoprene suits proved efficient in protecting swimmers against infection. PCR detection in rats revealed high Leptospira infection rates. Partial sequencing of the 16S gene and serology on both human and animal samples strongly suggests that rats were the main contaminators and were likely at the origin of the infection in humans.

Resurgence of bedbugs in southern France: a local problem or the tip of the iceberg?

BACKGROUND: Bedbugs (Cimex lectularius) have been feeding on sleeping human beings since prehistory. In Europe, bed bugs were common and endemic until World War II when improved body and home hygiene, and widespread use of insecticides led to almost complete eradication. Current evidence indicates that bedbugs are making a comeback in Europe, USA, Canada and Australia. In our practice in Southern France, we observed several cases within a period of only 1 year. OBJECTIVES: Based on this experience, we conducted an epidemiological study to evaluate the status of bedbugs in France. METHODS: During summer 2009, we mailed a short questionnaire to all hospital professors in the CEDEF (Collège des Enseignants de Dermatologie de France) asking four questions: number of suspected diagnosis of bedbugs in the year 2009, and number of certain positive diagnosis, difficulties in treatment, use of a pest control professional for treatment, and finally personal opinion on actual incidence of bedbugs, compared with past years. RESULTS: Of the 84 questionnaires sent, there were only 26 responses despite two reminders. The responses were predominantly southern France, probably as a result of intensive immigration and increased travel and trade. Difficulties encountered during diagnosis and treatment are also mentioned. Utilizing the services of entomological experts and pest control professionals is essential. CONCLUSIONS: France has the same experience regarding the resurgence of bedbugs as several European countries, USA, Canada and Australia, especially the southern regions. This emerging health problem has to be known by dermatologists. A national programme has been launched in France to assess actual incidence and study C. lectularius- related diseases.

Emergence of murine typhus in La Réunion, France, 2012-2017.

OBJECTIVE: Murine typhus (MT) is an acute zoonosis caused by Rickettsia typhi, a flea-borne rickettsiosis. The first autochthonous case was reported in 2012. Once autochthonous transmission of Rickettsia typhi was proven, we performed a prospective study to describe and raise awareness of this often-misdiagnosed disease among physicians. PATIENTS AND METHODS: We performed a prospective observational study of MT cases in La Réunion from 2012 to 2017. MT cases were defined as clinically compatible illnesses with a specific positive serology and/or PCR. RESULTS: Sixty-one confirmed cases were collected. The main clinical features were prolonged fever (90%), asthenia (87%), and headaches (79%). The main biological abnormalities were elevated liver enzymes (84%) and thrombopenia (75%). Renal function was normal in 90% of cases; it was an important feature because leptospirosis is a frequent cause of acute renal failure. A seasonal factor was observed with 79% of cases reported in the warm season and most of them in the west and south of the island (i.e., the dry areas). CONCLUSION: MT is an emerging disease in La Réunion, and local conditions could lead to an endemic situation. Cases of acute undifferentiated fever with headaches should guide to the diagnosis of MT especially in the warm season and dry areas. Leptospirosis is an alternative diagnosis, which differs from MT by its epidemiological characteristics and by the associated frequent renal dysfunction.

[Vector control for armed forces: a historical requirement requiring continual adaptation]. / La lutte antivectorielle dans les armées: une nécessité historique, une adaptation indispensable.

From time immemorial vector-borne diseases have decimated the fighting capacity of armies and caused suspension or cancellation of military operations. For this reason vector control strategies have always been a major requirement in ensuring the operational readiness of armed forces. Using malaria as an example, this article provides an update on vector control methods used by the French army in terms of available tools and of their applications in function of the operational situation. In coming years vector control strategies must be modernized not only by assessing vector-borne disease threats in the field and improving resources available to troops but also by professionalizing this service by creating specialized units.

[Evaluation of the anopheline mosquito aggressivity and of malaria transmission risk: methods used in French Army]. / Evaluation de l'agressivité des anophèles et du risque de transmission du paludisme: méthodes utilisées dans les Armées françaises.

Identification of the anopheline mosquito species involved in local transmission as well as knowledge of its biology and behavior is necessary for malaria vector control. To allow such study, two methods are usually used to capture adult mosquitoes, i.e., night catches on human volunteers and light-trap collections with human bait. The purpose of this article is to describe these two methods including their advantages and disadvantages as well as a method of surveying breeding sites as implemented by French Army personnel.

[Contribution of remote sensing to malaria control]. / Apport de la télédétection à la lutte contre le paludisme.

Despite national and international efforts, malaria remains a major public health problem and the fight to control the disease is confronted by numerous hurdles. Study of space and time dynamics of malaria is necessary as a basis for making appropriate decision and prioritizing intervention including in areas where field data are rare and sanitary information systems are inadequate. Evaluation of malarial risk should also help anticipate the risk of epidemics as a basis for early warning systems. Since 1960-70 civilian satellites launched for earth observation have been providing information for the measuring or evaluating geo-climatic and anthropogenic factors related to malaria transmission and burden. Remotely sensed data gathered for several civilian or military studies have allowed setup of entomological, parasitological, and epidemiological risk models and maps for rural and urban areas. Mapping of human populations at risk has also benefited from remotely sensing. The results of the published studies show that remote sensing is a suitable tool for optimizing planning, efficacy and efficiency of malaria control.

[Bedbugs (Heteroptera, Cimicidae): biting again]. / Les punaises de lits (Heteroptera, Cimicidae): une actualité "envahissante".

Bedbugs have been man's faithful companions from his cave days to the present time. After World War II, improvements in household and personal cleanliness and above all widespread use of insecticidal treatment led to a decline in the prevalence of bedbugs so that they became almost unknown to populations in industrialized countries. However in recent years a resurgence of bedbugs has been reported in North America as well as in most European countries. The purpose of this study is to provide an update on the comeback of bedbugs in France and the world, to discuss their impact on public health, and to consider possible causes for the current resurgence.

[Update on Dermatobia hominis: South American furuncular myiasis]. / Le point sur Dermatobia hominis: myiase "furonculeuse" d'Amérique du Sud.

Furuncular myiasis is an infestation of the skin caused by Dermatobia hominis larvae known as "ver macaque" in French Guyana, "berne" in Brazil, "torsalo" in Colombia, or "human botfly" in English-language literature. It has identical features in man and domestic mammals. The primary lesion consists of a boil-like inflammatory papule with a central punctum exuding a serosanguinous discharge. The respiratory sinus of the D. hominis larvae may be visible through the punctum. Myiasis secondary to D. hominis accounts for 10% of imported tropical dermatosis observed in Paris. Diagnosis of furuncular myiasis should be considered in any patient with a history of travel or residence in an endemic area. Treatment depends mainly on mechanical removal that may be facilitated by injection of lidocaine into the lesion or prior application of a 1% solution of ivermectin.

[Ticks and human tick-borne diseases in Africa]. / Tiques et maladies transmises à l'homme en Afrique.

Ticks are obligate hematophagous arthropod parasites that feed on the blood of every class of vertebrates in almost every region of the world. Tick bites can transmit bacterial, viral and parasitic diseases to humans. In this review we describe ticks and human tick-borne diseases in Africa. The first part of this article presents elements linking the morphology and biology of these acarians as well as various aspects of their taxonomy and phylogeny. The next part of the article describes the main human tick borne diseases in Africa with particular focus on spotted fever group rickettsioses, relapsing fever borrelioses, and Crimean-Congo fever. Information is also provided on Q fever and other tick-borne diseases as ehrlichioses, anaplasmoses, Lyme disease, and babesiosis that can and do occur in Africa. Finally this article describes methods used for the collection and identification of ticks and for control and prevention of tick bites as well as essential points for early diagnosis and management of patients who have been bitten by ticks.

[Potential immunologic consequences of lymph node dissection in colorectal cancer]. / Implications immunologiques potentielles du curage ganglionnaire: Exemple du cancer colorectal.

Lymph node dissection is an integral part of the surgical resection of colon cancers; it completes the wide regional resection of tumor and it allows prognostic evaluation through accurate staging. Studies have demonstrated an immune reaction to the tumoral site which attests to an ongoing dialog between the tumor and systemic defenses. The regional lymph nodes constitute an important first line of immune defense where initial host response is initiated or, inversely, they may participate in a local state of immunosuppression. This article reviews current knowledge on intra-tumoral and nodal immune status in colorectal cancers and attempts to evaluate the potential immunologic implications of lymph node dissection.

[Not Available]. / Implications immunologiques potentielles du curage ganglionnaire : Exemple du cancer colorectal.

F. Pagès, A. Berger, F. Zinzindohoué, A. Kirilovsky, J. Galon, W.-H. Fridman Lymph node dissection is an integral part of the surgical resection of colon cancers; it completes the wide regional resection of tumor and it allows prognostic evaluation through accurate staging. Studies have demonstrated an immune reaction to the tumoral site which attests to an ongoing dialog between the tumor and systemic defenses. The regional lymph nodes constitute an important first line of immune defense where initial host response is initiated or, inversely, they may participate in a local state of immunosuppression. This article reviews current knowledge on intra-tumoral and nodal immune status in colorectal cancers and attempts to evaluate the potential immunologic implications of lymph node dissection.

[Not Available]. / Implications immunologiques potentielles du curage ganglionnaire : Exemple du cancer colorectal.

F. Pagès, A. Berger, F. Zinzindohoué, A. Kirilovsky, J. Galon, W.-H. Fridman Lymph node dissection is an integral part of the surgical resection of colon cancers; it completes the wide regional resection of tumor and it allows prognostic evaluation through accurate staging. Studies have demonstrated an immune reaction to the tumoral site which attests to an ongoing dialog between the tumor and systemic defenses. The regional lymph nodes constitute an important first line of immune defense where initial host response is initiated or, inversely, they may participate in a local state of immunosuppression. This article reviews current knowledge on intra-tumoral and nodal immune status in colorectal cancers and attempts to evaluate the potential immunologic implications of lymph node dissection.

Morphogen gradients. A question of time or concentration?

Morphogens are secreted proteins that organize surrounding tissues into distinct territories and are thought to act as a function of a threshold of their concentration. Although it has been demonstrated that morphogens act directly on the cells and do not rely on secondary signalling relays, intracellular sequential induction mechanisms, which are dependent on a simple signalling instruction, have not been excluded. Here, we present an alternative model to account for the organizing properties of morphogens, and propose that initial exposure to signalling changes cell context, which in combination with continuing morphogen activity, results in the expression of novel targets.

First record of Aedes albopictus in Gabon.

Aedes albopictus were collected in the French military camp of Libreville, Estuaire Province, Gabon, from January to March 2007 by human landing catches during an entomological evaluation of malaria transmission. Inspection of potential larval habitats within and outside the camp showed that Ae. albopictus was found only in artificial containers (discarded tires and small water containers). Associated species of mosquito larvae were Ae. aegypti (L.) and Culex quinquefasciatus. At the same time, Ae. albopictus adults and larvae were also collected from discarded tires in Tcheungue near Port Gentil, Ogoue Maritime Province. Ae. albopictus seems to be established in this part of Gabon's littoral. Further studies are necessary to investigate the extension of Ae. albopictus establishment throughout the country.

[Triatominae: growing trend to domesticity]. / Les Triatominae: une domestication qui se généralise.

Triatominae are biting hematophageous insects that have been wild vectors of the parasite Trypanosoma curzi for thousands of years. The arrival of man with his cortege of domestic animals and impact on the natural environment led these insects to adapt to the human environment so well that many species are now domesticated. Insect extermination programs have allowed satisfactory control of parasite transmission but have also promoted replacement of the exterminated species by species that were once semi-domestic or wild.