The prognostic value of minimally involved melanoma sentinel lymph nodes

Introduction: la biopsie du ganglion sentinelle (GS) est une procédure reconnue et fiable pour établir le stade ganglionnaire du mélanome cutané. Le GS est le facteur pronostique le plus puissant pour la survie des patients atteints d'un mélanome à risque intermédiaire, cliniquement localisé. Celui-ci est métastatique dans environ 15-30% des cas. Lorsque le GS est positif, un curage de l'aire ganglionnaire concernée est généralement entrepris. Néanmoins, seuls 20-25% de ces patients présentent des ganglions non-sentinelles (GNS) métastatiques. Ces données suggèrent que le curage, et les risques opératoires qui y sont associés, n'est peut-être pas nécessaire chez le trois-quarts de ces patients. Un autre aspect est que l'impact sur la survie des curages basé sur le résultat du GS n'est pas clairement démontré. La nécessité de ce curage d'emblé est actuellement en cours d'évaluation par un protocole international (Multicenter Selective Lymphadenectomy Trial II : MSLT II). Plusieurs auteurs ont essayé de classifier la charge tumorale du GS afin d'évaluer s'il était possible d'épargner le curage à certains patients et de mieux affiner ce facteur pronostic sans succès. En 2009, le Groupe Mélanome de l'EORTC (European Organisation for Research and Treatment of Cancer) a recommandé un protocole d'évaluation anatomopathologique du GS-positif en trois items: (1) la localisation micro-anatomique des métastases à l'intérieur du ganglion selon Dewar (A = sous-capsulaire, B = combinée sous-capsulaire and parenchymateuse, C = parenchymateuse, D = multifocale, and'E = extensive) ; (2) la mesure de la taille tumorale dans le ganglion selon les critères de Rotterdam pour le diamètre maximal. Le diamètre de la plus grande métastase est exprimé en nombre absolu et (3) la taille tumorale stratifiée par catégories : <0.1mm, 0.1-1.0mm et >1.0 mm. Le but de cette étude rétrospective d'une cohorte de patients, était d'investiguer les résultats des GS-positifs et d'analyser les facteurs pronostiques de la survie à la lumière des recommandations de l'EORTC. Ainsi que de comparer les sous-groupes du GS-positif avec une invasion minimale (taille tumorale <0.1mm et/ou atteinte sous-capsulaire) avec le GS-négatif. Les facteurs pouvant prédire la présence de GNS- positif ont également été analysés. Matériel et méthode : une étude des dossiers a été réalisée pour les 499 patients consécutifs entre 1997 et 2008 qui ont eu une biopsie du GS dans notre institution. Le dégrée d'envahissement du GS-positif a été entièrement revue par l'équipe référente de l'Institut de Pathologie (Dresse E. Saiji et Dresse H. Bouzourène) selon les recommandations de l'EORTC. Des analyses univariées et multivariées des potentiels facteuis pronostics ont été réalisées. Des analyses de survie ont également été effectuées avec des courbes d'estimation de Kaplan-Meier combinées à une régression de Cox. Le protocole a été accepté par la Commission d'Ethique. Résultats: un GS-positif a été trouvé chez 123 (25%) patients panni les 499 qui ont bénéficié d'une biopsie. Avec un suivi médian de 52 mois, la survie à 5 ans sans récidive (SSR), spécifique à la maladie (SS) et globale (SG) étaient de 88%, 94%, et 90% respectivement pour les patients avec GS-négatif. Concernant les GS avec invasion minimale, 21 patients étaient dans le sous-groupe <0.1 mm selon les critères de Rotterdam et 52 patients dans le sous-groupe sous-capsulaire selon Dewar. La survie dans ces deux sous-groupes était de 80% et 57% pour la SSR, 87% et 70% pour la SS, 87% et 68% pour la SG, respectivement. L'analyse multivariée des GS-positifs a montré que les facteuis suivants influençaient significativement la survie (SSR, SS et SG): l'épaisseur selon Breslow de la tumeur primaire (p=0.002, 0.006, 0.004), la taille tumorale du GS-positif >0.1 mm (p= 0.01, 0.04, 0.03), le genre masculin (p=0.06, 0.005, 0.002) et l'ulcération de la tumeur primaire (p=0.05, 0.03, 0.007). L'analyse des sous-groupes avec invasion minimale n'a pas permis d'établir de facteur pour prédire la négativité des GNSs. Conclusion: La classification du GS-positif par la taille tumorale selon les critères de Rotterdam est un facteur pronostique simple et utile pour évaluer la survie des patients atteints de mélanome. Nous avons observé une tendance (non statistiquement significative) d'une survie diminuée pour le sous-groupe des patients avec GS-positif et une taille de la métastase <0.1 mm comparée à celle des patients avec GS-négatif. Ceci nous incite à conclure que ce sous-groupe de patients ne devrait pas être assimilé et traité comme ceux qui ont un GS-négatif. D'autre part nos résultats montrent que la localisation micro-anatomique selon Dewar n'est pas un outil pronostique utile pour évaluer la survie, ni pour prédire le status des GNSs.

The role of interval nodes in sentinel lymph node mapping and dissection for melanoma patients.

In sentinel node (SN) biopsy, an interval SN is defined as a lymph node or group of lymph nodes located between the primary melanoma and an anatomically well-defined lymph node group directly draining the skin. As shown in previous reports, these interval SNs seem to be at the same metastatic risk as are SNs in the usual, classic areas. This study aimed to review the incidence, lymphatic anatomy, and metastatic risk of interval SNs. METHODS: SN biopsy was performed at a tertiary center by a single surgical team on a cohort of 402 consecutive patients with primary melanoma. The triple technique of localization was used-that is, lymphoscintigraphy, blue dye, and gamma-probe. Otolaryngologic melanoma and mucosal melanoma were excluded from this analysis. SNs were examined by serial sectioning and immunohistochemistry. All patients with metastatic SNs were recommended to undergo a radical selective lymph node dissection. RESULTS: The primary locations of the melanomas included the trunk (188), an upper limb (67), or a lower limb (147). Overall, 97 (24.1%) of the 402 SNs were metastatic. Interval SNs were observed in 18 patients, in all but 2 of whom classic SNs were also found. The location of the primary was truncal in 11 (61%) of the 18, upper limb in 5, and lower limb in 2. One patient with a dorsal melanoma had drainage exclusively in a cervicoscapular area that was shown on removal to contain not lymph node tissue but only a blue lymph channel without tumor cells. Apart from the interval SN, 13 patients had 1 classic SN area and 3 patients 2 classic SN areas. Of the 18 patients, 2 had at least 1 metastatic interval SN and 2 had a classic SN that was metastatic; overall, 4 (22.2%) of 18 patients were node-positive. CONCLUSION: We found that 2 of 18 interval SNs were metastatic: This study showed that preoperative lymphoscintigraphy must review all known lymphatic areas in order to exclude an interval SN.

Successful migration of three tracers without identification of sentinel nodes during intraoperative lymphatic mapping for non-small cell lung cancer.

Prospective comparative evaluation of patent V blue, fluorescein and (99m)TC-nanocolloids for intraoperative sentinel lymph node (SLN) mapping during surgery for non-small cell lung cancer (NSCLC). Ten patients with peripherally localised clinical stage I NSCLC underwent thoracotomy and peritumoral subpleural injection of 2 ml of patent V blue dye, 1 ml of 10% fluorescein and 1ml of (99m)Tc-nanocolloids (0.4 mCi). The migration and spatial distribution pattern of the tracers was assessed by direct visualisation (patent V blue), visualisation of fluorescence signalling by a lamp of Wood (fluorescein) and radioactivity counting with a hand held gamma-probe ((99m)Tc-nanocolloids). Lymph nodes at interlobar (ATS 11), hilar (ATS 10) and mediastinal (right ATS 2,4,7; left ATS 5,6,7) levels were systematically assessed every 10 min up to 60 min after injection, followed by lobectomy and formal lymph node dissection. Successful migration from the peritumoral area to the mediastinum was observed for all three tracers up to 60 min after injection. The interlobar lympho-fatty tissue (station ATS 11) revealed an early and preferential accumulation of all three tracers for all tumours assessed and irrespective of the tumour localisation. However, no preferential accumulation in one or two distinct lymph nodes was observed up to 60 min after injection for all three tracers assessed. Intraoperative SLN mapping revealed successful migration of the tracers from the site of peritumoral injection to the mediastinum, but in a diffuse pattern without preferential accumulation in sentinel lymph nodes.

Prognostic value of sentinel node biopsy in 327 prospective melanoma patients from a single institution

Résumé Etude de la valeur pronostique de la biopsie du ganglion sentinelle dans une étude prospective monocentrique de 327 patients atteints de mélanome malin But II s'agit de confirmer la validité de la biopsie du ganglion sentinelle, d'en définir la morbidité, d'investiguer les facteurs prédictifs pour le statut du ganglion sentinelle ainsi que de déterminer les facteurs pronostiques pour la survie sans récidive et la survie spécifique liée à la maladie. Matériel et méthode D'octobre 1997 à décembre 2004, 327 patients consécutifs présentant un mélanome cutané primaire des membres, du tronc et de la tête, sans adénopathie clinique ni métastase à distance ont été inclus. La biopsie du ganglion sentinelle a été réalisée selon la triple technique (lymphoscintigraphie, colorant bleu vital et sonde de détection gamma). Les paramètres et la survie ont été évalués par différentes analyses de régression logistique multiple selon Cox et la survie évaluée selon Kaplan Meier. Résultats Vingt-trois pour cent des patients présentaient au moins un ganglion sentinelle métastatique, ce qui était associé de façon significative à l'épaisseur selon Breslow (p<0.001). Le taux de succès de la biopsie du ganglion sentinelle était de 99.1% et sa morbidité de 7.6%. Avec une durée médiane de suivi de 33 mois, la survie sans récidive à 5 ans était de 43% pour les patients avec un ganglion sentinelle positif et de 83.5% pour ceux avec un ganglion sentinelle négatif. La survie spécifique liée à la maladie à 5 ans était de 49% pour les patients avec un ganglion sentinelle positif et de 87.4% pour ceux avec un ganglion sentinelle négatif. Le taux de faux négatif de la biopsie du ganglion sentinelle était de 8.6%. L'analyse multivariée a démontré que la survie sans récidive était significativement péjorée par :l'épaisseur selon Breslow (RR=5.6, p<0.001), un ganglion sentinelle positif (RR=5.0, p<0.001), et le sexe masculin (RR=2.9, p=0.001). La survie spécifique liée à la maladie était significativement diminuée par : un ganglion sentinelle métastatique (RR=8.4, p<O.OOI), le sexe masculin (RR=6.1, p<0.001), l'épaisseur selon Breslow (RR=3.2, p=0.013), et la présence d'une ulcération (RR=2.6, p=0.015). Conclusion La biopsie du ganglion sentinelle est une procédure fiable avec une haute sensibilité (91.4%) et une faible morbidité (7.6%). L'épaisseur selon Breslow était le seul facteur prédictif significatif pour le statut du ganglion sentinelle. La survie sans récidive était péjorée selon un ordre décroissant par :l'épaisseur selon Breslow, un ganglion sentinelle métastatique, et le sexe masculin. De façon similaire la survie spécifique liée à la maladie était péjorée par : un ganglion sentinelle métastatique, le sexe masculin, l'épaisseur selon Breslow, et une ulcération. Ces données renforcent le statut du ganglion sentinelle en tant que puissant moyen pour évaluer le stade tumoral ainsi que le pronostic.

Medication incidents in primary care medicine: protocol of a study by the Swiss Federal Sentinel Reporting System.

BACKGROUND/RATIONALE: Patient safety is a major concern in healthcare systems worldwide. Although most safety research has been conducted in the inpatient setting, evidence indicates that medical errors and adverse events are a threat to patients in the primary care setting as well. Since information about the frequency and outcomes of safety incidents in primary care is required, the goals of this study are to describe the type, frequency, seasonal and regional distribution of medication incidents in primary care in Switzerland and to elucidate possible risk factors for medication incidents. Label="METHODS AND ANALYSIS" ="METHODS"/> <AbstractText STUDY DESIGN AND SETTING: We will conduct a prospective surveillance study to identify cases of medication incidents among primary care patients in Switzerland over the course of the year 2015. PARTICIPANTS: Patients undergoing drug treatment by 167 general practitioners or paediatricians reporting to the Swiss Federal Sentinel Reporting System. INCLUSION CRITERIA: Any erroneous event, as defined by the physician, related to the medication process and interfering with normal treatment course. EXCLUSION CRITERIA: Lack of treatment effect, adverse drug reactions or drug-drug or drug-disease interactions without detectable treatment error. PRIMARY OUTCOME: Medication incidents. RISK FACTORS: Age, gender, polymedication, morbidity, care dependency, hospitalisation. STATISTICAL ANALYSIS: Descriptive statistics to assess type, frequency, seasonal and regional distribution of medication incidents and logistic regression to assess their association with potential risk factors. Estimated sample size: 500 medication incidents. LIMITATIONS: We will take into account under-reporting and selective reporting among others as potential sources of bias or imprecision when interpreting the results. ETHICS AND DISSEMINATION: No formal request was necessary because of fully anonymised data. The results will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT0229537.

Emergent patterns of social organization in captive Cercocebus torquatus: Testing the GrooFiWorld agent-based model

We empirically applied the GrooFiWorld agent-based model (Puga-González et al. 2009) in a group of captive mangabeys (Cercocebus torquatus). We analysed several measurements related to aggression and affiliative patterns. The group adopted a combination of despotic and egalitarian behaviours resulting from the behavioural flexibility observed in the Cercopithecinae subfamily. Our study also demonstrates that the GrooFiWorld agent-based model can be extended to other members of the Cercopithecinae subfamily generating parsimonious hypotheses related to the social organization.

Agonistic strategies and spatial distribution in captive sooty mangabeys (Cercocebus atys lunulatus)

The aim of this article is to study the relationship between the dominance hierarchy and the spatial distribution of a group of captive sooty mangabeys (Cercocebus atys). The analysis of the spatial distribution of individuals in relation to their rank in the dominance hierarchy showed a clear linear hierarchy in which the dominant individual was located in central positions with regard to the rest of the group members. The large open enclosure where the group was living allowed them to adopt a high-risk agonistic strategy in which individuals attacked other individuals whose rank was significantly different from their own. The comparison of the results with a previous study of mangabeys showed that, although the dominance ranks of both groups were similar, the fact that they lived in facilities with different layouts caused different agonistic strategies to emerge and allowed the dominant individual to assume different spatial locations.

Clinically occult metastases in patients with cutaneous melanoma. Detection with sentinel lymph node biopsy and whole body positron emission tomography

Objective: The aim of this study was to investigate the use of sentinel lymph node biopsy (SLNB) and whole body positron emission tomography (PET), with emphasis on surgical treatment and prognosis, in the detection of clinically occult metastases in patients with clinically localized cutaneous melanoma. Patients and methods: The study population consisted of 1255 patients with clinical stage I–II cutaneous melanoma, operated at Turku University Hospital between 1983 and 2007. 334 patients underwent SLNB and they were compared to 921 retrospective patients. A subgroup of 30 symptom-free patients with high risk melanoma underwent prospectively whole body PET 6–24 months postoperatively. Results: Overall, the disease-specific survival rate was 84.4 % at five years. Sex, Breslow thickness, age and nodal status were independent prognostic factors for survival. SLNB revealed occult nodal metastases in 17 % of the patients. There was no significant difference in disease-specific overall survival between SLNB patients and controls, but the nodal disease-free time was significantly longer suggesting better local control after SLNB and subsequent completion lymph node dissection. The followup time was different between the study cohorts and initial surgery was performed during different time periods. SLNB detected micrometastases in seven of 155 patients (4.5 %) with thin T1 primary melanoma and in four of 25 patients (16 %) with head and neck melanoma. In six of 30 asymptomatic patients with high risk melanoma (20 %), whole body PET detected occult distant metastases. Conclusion: Both SLNB and whole body PET were reliable methods to detect clinically occult metastases in patients with cutaneous melanoma. This upstaging altered the treatment in each case.

La captive

Soitinnus: Lauluääni (sopraano), ork.

Localization of metastasis within the sentinel lymph node biopsies: a predictor of additional axillary spread of breast cancer?

PURPOSE: To explore the relationship between morphological characteristics and histologic localization of metastasis within sentinel lymph nodes (SLN) and axillary spread in women with breast cancer. METHODS: We selected 119 patients with positive SLN submitted to complete axillary lymph node dissection from July 2002 to March 2007. We retrieved the age of patients and the primary tumor size. In the primary tumor, we evaluated histologic and nuclear grade, and peritumoral vascular invasion (PVI). In SLNs we evaluated the size of metastasis, their localization in the lymph node, number of foci, number of involved lymph nodes, and extranodal extension. RESULTS: Fifty-one (42.8%) patients had confirmed additional metastasis in non-sentinel lymph nodes (NLSN). High histologic grade, PVI, intraparenchymatous metastasis, extranodal neoplastic extension and size of metastasis were associated with positive NLSN. SLN metastasis affecting the capsule were associated to low risk incidence of additional metastasis. After multivariate analysis, PVI and metastasis size in the SLN remained as the most important risk factors for additional metastasis. CONCLUSIONS:The risk of additional involvement of NSLN is higher in patients with PVI and it increases progressively according the histologic localization in the lymph node, from capsule, where the afferent lymphatic channel arrives, to the opposite side of capsule promoting the extranodal extension. Size of metastasis greater than 6.0 mm presents higher risk of additional lymph node metastasis.

Myocardial stereology in captive Callithrix kuhlii (Callitrichidae, Primates): healthy animals versus animals affected by wasting marmoset syndrome (WMS)

This study comprised 12 hearts of Wied´s black-tufted-ear marmoset, Callithrix kuhlii (Coimbra-Filho 1985), 6 with Wasting Marmoset Syndrome (WMS) and 6 non-affected. Biometry was performed after death. After necropsy, the hearts were weighed, dissected, fixed in 10% formalin solution (pH 7.2), and processed for optical microscopy at 5µm sections stained with Haematoxylin-Eosin. Quantitative analysis was performed by stereological techniques. The statistical differences between the biometrical and stereological parameters were assessed by the Mann-Whitney test. The morphometric results showed that WMS causes a significant reduction in body and cardiac weights, and also in the volume density of vessels in those animals. Further studies are necessary to understand some of the results shown here.

Anti-Rickettsia spp. antibodies in free-ranging and captive capybaras from southern Brazil

Capybaras (Hydrochaeris hydrochaeris) are among the main hosts of Amblyomma spp. ticks, which is able to transmit Rickettsia species to human beings and animals. Since they are often infested with potential vector ticks, capybaras may be used as sentinels for rickettsiosis, such as the Brazilian Spotted Fever. The aim of the present study was to determine the prevalence of antibodies against Rickettsia spp. using the indirect immunofluorescence assay (IFA) in 21 free-ranging and 10 captive animals from the Zoological Park of the 'Bela Vista Biological Sanctuary' (BVBS), Itaipu Binational, Foz do Iguaçu, Southern Brazil. Antigens of six rickettsial species already identified in Brazil (Rickettsia rickettsii, R. parkeri, R. bellii, R. rhipicephali, R. amblyommii and R. felis) were used for IFA. Ticks from each capybara were collected for posterior taxonomic identification. A total of 19 (61.3%) samples reacted to at least one of tested species. Seropositivity was found in 14 (45.2%), 12 (38.7%), 5 (16.1%), 4 (12.9%), 3 (9.7%) and 3 (9.7%) animals for R. rickettsii, R. bellii, R. parkeri, R. amblyommii, R. felis and R. rhipicephali, respectively. Two captive capybaras presented suggestive titers of R. rickettsii infection and one sample showed homologous reaction to R. parkeri. Only one free-ranging capybara presented evidence R. bellii infection. Ticks collected on capybaras were identified as Amblyomma dubitatum e Amblyomma sp. Results evidenced the rickettsial circulation in the area, suggesting a potential role of capybaras on bacterial life cycle.

Hematologic, serum biochemistry and urinary values for captive Crab-eating Fox (Cerdocyon thous) in São Paulo state, Brazil

The importance of studies with hematological, serum biochemistry and urinary values of Crab-eating Fox (Cerdocyon thous) is based on the need for health care and maintenance of those populations. This paper has the objective to investigate hematological, serum biochemistry and urinary physiological parameters of the Crab-eating fox, comparing gender and age differences. Blood samples were collected in 2003 from 52 animals of different Zoos in São Paulo state, Brazil; 7mL of blood was used to obtain a complete blood cell count (CBC) and the profile of the serum biochemistry. Moreover, 5mL of urine were collected for analysis. There was no difference in values for male and female animals, as for the CBC and serum biochemistry. Some hematological and serum biochemical parameters were influenced by age, showing significant differences. Urinalysis results were just demonstrated in a descriptive form. The studied values were, RBC 4.35±0.73 x 10(6) /µL, WBC 7.72±3.66 x 10³ /µL (predominance of segmented neutrophils), platelets 227.06±111.58 x 10³ /µL, urea 43.06±14.28mg/dL and creatinine 1.03±0.24mg/dL. Hematological, serum biochemistry and urinary values obtained in this study can be used as physiological values of the captive Crab-eating Fox. It is possible to conclude that wild species need their own reference values, differentiating animals in captivity from free-ranging animals.

Molecular detection of enteropathogenic Escherichia coli in asymptomatic captive psittacines

Psittaciformes are one of the most endangered groups of birds, and several Brazilian species are classified between vulnerable and critically endangered. It is thus necessary to identify agents that cause infections in captive wild animals and to assess the risks posed thereof and to design interventions to minimize the possibility of disease outbreaks, leading to the conservation of endangered species. The purpose of this study was to identify enteropathogenic Escherichia coli (EPEC) cloacal isolates from asymptomatic psittacines in captivity and evaluate the distribution of the EPEC pathotype. Cloacal swabs were obtained from 46 asymptomatic birds, and resulting isolates were tested by polymerase chain reaction (PCR) for the presence of the attaching and effacing gene (eae) and bundle-forming pilus structural gene (bfpA) of EPEC. Samples from several species were tested, and three samples were found to be positive for the eae and bfpA genes and characterized as typical EPEC. This is the first report of this pathotype in asymptomatic psittacines. Although certain E. coli strains are more pathogenic than others, various factors should be considered when determining the potential of E. coli isolates to cause disease in captive psittacines. Birds that are positive for the EPEC (typical) strain could be zoonotic sources of infection, and may have acquired these strains through contact with humans or domestic animals. These findings may also be valuable for the long-term management of endangered species ex situ as one EPEC sample was isolated from a Red-tailed Amazon (Amazona brasiliensis).

Isospora bocamontensis (Protozoa: Apicomplexa) in captive yellow cardinal Gubernatrix cristata (Passeriformes: Emberezidae)

The yellow cardinal (Gubernatrix cristata) is a passerine found in southern Brazil, especially along the border with Uruguay and Argentina. It is an endangered species and its population is decreasing. Among the parasites that affect passerines, the genus Isospora is the most easily found in both captive and free-living birds. This parasite commonly causes injury to the intestinal tissue and could occasionally affect other organs. In this work we examined the occurrence of coccidiosis in captive yellow cardinals and its association with factors such as sex, use of parasiticides, type of enclosure, contact with feces, type of food and cleaning frequency. We collected fecal samples of 45 yellow cardinals, healthy and kept in captivity, in late afternoon at the end of the reproductive period. The examination showed parasitic infection by Isospora bocamontensis in 44.5% of the birds. This infection is not influenced by the sex of birds, but is significantly affected by the type of enclosure, contact with the feces, use of parasiticides, type of food and cleaning frequency. The results indicate that to keep yellow cardinals captive, these factors must be observed.