Improved nationwide survival of sarcoma patients with a network of reference centers.

BACKGROUND: We investigated the impact of the implementation of a network of reference centers for sarcomas (NETSARC) on the care and survival of sarcoma patients in France since 2010. PATIENTS AND METHODS: NETSARC (netsarc.org) is a network of 26 reference sarcoma centers with specialized multidisciplinary tumor boards (MDTBs), funded by the French National Cancer Institute (INCa) since 2010. Its aims are to improve the quality of diagnosis and care of sarcoma patients. Patients' characteristics, treatments, and outcomes are collected in a nationwide database. The objective of this analysis was to compare the survival of patients in three periods: 2010-2012 (non-exhaustive), 2013-2015, and 2016-2020. RESULTS: A total of 43 975 patients with sarcomas, gastrointestinal stromal tumors (GISTs), or connective tissue tumors of intermediate malignancy were included in the NETSARC+ database since 2010 (n = 9266 before 2013, n = 12 274 between 2013 and 2015, n = 22 435 in 2016-2020). Median age was 56 years, 50.5% were women, and 13.2% had metastasis at diagnosis. Overall survival was significantly superior in the period 2016-2020 versus 2013-2015 versus 2010-2012 for the entire population, for patients >18 years of age, and for both metastatic and non-metastatic patients in univariate and multivariate analyses (P < 0.0001). Over the three periods, we observed a significantly improved compliance to clinical practice guidelines (CPGs) nationwide: the proportion of patients biopsied before surgery increased from 62.9% to 72.6%; the percentage of patients presented to NETSARC MDTBs before first surgery increased from 31.7% to 44.4% (P < 0.0001). The proportion of patients with R0 resection on first surgery increased (from 36.1% to 46.6%), while R2 resection rate decreased (from 10.9% to 7.9%), with a better compliance and improvement in NETSARC centers. CONCLUSIONS: The implementation of the national reference network for sarcoma was associated with an improvement of overall survival and compliance to guidelines nationwide in sarcoma patients. Referral to expert networks for sarcoma patients should be encouraged, though a better compliance to CPGs can still be achieved.

Evaluation of two modalities of perioperative treatment in the management of extremity and truncal soft tissue sarcomas: neoadjuvant concurrent chemoradiotherapy and sequential treatment.

PURPOSE: Patients with locally advanced grade 2-3 extremity/truncal soft tissue sarcomas (STS) are at high risk of recurrence. The objective of this study was to assess the efficacy and feasibility of neoadjuvant concurrent chemoradiotherapy (cCRT) in selected grade 2-3 patients with limb or trunk wall STS, and to compare this schedule to a sequential approach combining neoadjuvant chemotherapy and adjuvant radiotherapy. METHODS: We retrospectively included patients who underwent neoadjuvant cCRT at two comprehensive cancer centers from 1992-2016. We then compared these results to those of patients treated with preoperative chemotherapy and postoperative radiotherapy from a third comprehensive cancer center with a propensity score matched analysis. RESULTS: A total of 53 patients were treated by neoadjuvant cCRT; 58 patients could be matched with 29 patients in each treatment group after propensity score matching. Disease-free survival and overall survival at 5 years were 54.9 and 63.5%, respectively with neoadjuvant cCRT, with no significant difference when compared to the sequential treatment group. R0 resection rate was higher (90.9 vs 44.8%, p < 0.01) in the cCRT group than in the sequential treatment group during a shorter therapeutic sequence (118 vs 210.5 days, p < 0.01), with no impact on the surgical procedure or postoperative complications. CONCLUSION: cCRT is feasible with acceptable immediate and late toxicities. It could facilitate surgery by increasing the R0 resection rate and improve patient compliance by shortening the therapeutic sequence.

Validation of the Complexity INdex in SARComas prognostic signature on formalin-fixed, paraffin-embedded, soft-tissue sarcomas.

Background: Prediction of metastatic outcome in sarcomas is challenging for clinical management since they are aggressive and carry a high metastatic risk. A 67-gene expression signature, the Complexity INdex in SARComas (CINSARC), has been identified as a better prognostic factor than the reference pathological grade. Since it cannot be applied easily in standard laboratory practice, we assessed its prognostic value using nanoString on formalin-fixed, paraffin-embedded (FFPE) blocks to evaluate its potential in clinical routine practice and guided therapeutic management. Methods: A code set consisting of 67 probes derived from the 67 genes of the CINSARC signature was built and named NanoCind®. To compare the performance of RNA-seq and nanoString (NanoCind®), we used expressions of various sarcomas (n = 124, frozen samples) using both techniques and compared predictive values based on CINSARC risk groups and clinical annotations. We also used nanoString on FFPE blocks (n = 67) and matching frozen and FFPE samples (n = 45) to compare their level of agreement. Metastasis-free survival and agreement values in classification groups were evaluated. Results: CINSARC strongly predicted metastatic outcome using nanoString on frozen samples (HR = 2.9, 95% CI: 1.23-6.82) with similar risk-group classifications (86%). While more than 50% of FFPE blocks were not analyzable by RNA-seq owing to poor RNA quality, all samples were analyzable with nanoString. When similar (risk-group) classifications were measured with frozen tumors (RNA-seq) compared with FFPE blocks (84% agreement), the CINSARC signature was still a predictive factor of metastatic outcome with nanoString on FFPE samples (HR = 4.43, 95% CI: 1.25-15.72). Conclusion: CINSARC is a material-independent prognostic signature for metastatic outcome in sarcomas and outperforms histological grade. Unlike RNA-seq, nanoString is not influenced by the poor quality of RNA extracted from FFPE blocks. The CINSARC signature can potentially be used in combination with nanoString (NanoCind®) in routine clinical practice on FFPE blocks to predict metastatic outcome.

Eastern Canadian Colorectal Cancer Consensus Conference 2013: emerging therapies in the treatment of pancreatic, rectal, and colorectal cancers.

The annual Eastern Canadian Colorectal Cancer Consensus Conference held in Montreal, Quebec, 17-19 October 2013, marked the 10-year anniversary of this meeting that is attended by leaders in medical, radiation, and surgical oncology. The goal of the attendees is to improve the care of patients affected by gastrointestinal malignancies. Topics discussed during the conference included pancreatic cancer, rectal cancer, and metastatic colorectal cancer.

Soluble urokinase plasminogen activator receptor predicts mortality in patients with systemic inflammatory response syndrome.

OBJECTIVE: The soluble urokinase plasminogen activator receptor (suPAR) reflects inflammation. However, the prognostic value of suPAR measurements, particularly at the very early onset of systemic inflammatory response syndrome (SIRS), is less well defined. METHODS: The prognostic potential of suPAR levels in patients with SIRS was evaluated. From November 2010 until April 2013, 902 adult patients presenting with SIRS were investigated. Blood samples for laboratory testing of inflammation markers were collected simultaneously with initial blood cultures. suPAR testing was performed using suPARnostic(©) assay. RESULTS: Analyses of receiver operating characteristics curves revealed areas under the curve (AUCs) of 0.818 for predicting overall mortality within 48 h (36/902 patients died), 0.739 for 30-day mortality (117/902 died) and 0.706 for predicting 90-day mortality (151/902 died). AUCs for procalcitonin (0.777, 0.671 and 0.638), interleukin-6 (0.709, 0.593 and 0.569) and C-reactive protein (0.66, 0.594 and 0.586) as well as renal function and age were markedly lower. Using multivariable regression analyses, suPAR levels (P < 0.001) remained significant predictors of 48-h mortality, whereas suPAR levels (P < 0.001) and bacteraemia (P = 0.002 and P = 0.001, respectively) remained significant predictors of 30- and 90-day mortality. Using Kaplan-Meier survival plots, patients with suPAR <9.15 ng mL(-1) at SIRS onset had a clear benefit. CONCLUSION: suPAR plasma level determined at early SIRS is predictive for mortality.

Clinical presentation of Puumala virus infections in southern Austria in the peak year 2012.

In 2012, an extraordinary rise in Puumala infections causing nephropathia epidemica (NE) was observed in southern Austria. We investigated differences in epidemiology, clinical presentation, laboratory results, treatment parameters, and outcome between patients in 2012 and previous years (2007-2011). All patients diagnosed with Puumala virus infections between 2007 and 2012 using a point of care Puumala IgM test at the microbiology laboratory, Department of Internal Medicine, Medical University of Graz, were included. In 2012, 42 and in 2007-2011 a total of 40 patients were diagnosed with NE. In 2007-2011, patients presented more frequently with arthromyalgias (25% vs 7%, p = 0.027), while lower back pain was reported more often in 2012 (21% vs 5%, p = 0.029). Other symptoms occurred at the same rate. In 2012, patients were diagnosed significantly faster (time from first contact with a physician to diagnosis 1.3 ± 0.2 vs 2.7 ± 0.4 days, p = 0.01). Significantly fewer patients required haemodialysis in 2012 (2.4% vs 20%, p = 0.01). There were no significant differences in laboratory parameters between the two groups. In the peak year 2012, patients were diagnosed faster and fewer patients required haemodialysis possibly because of the earlier diagnosis and earlier onset of therapy.

Comparison of clinical presentation and laboratory values at admission between PCR-confirmed influenza A H1N1 infection and influenza-like disease, South-East Austria.

PURPOSE: Reliable and rapid diagnosis of influenza A H1N1 is essential to initiate the appropriate antiviral therapy and preventive measures. As PCR assays are time-consuming and rapid antigen tests have a limited sensitivity, official influenza case definitions are used in many clinical settings. These, however, are based exclusively on clinical criteria and have only a moderate potential to differentiate between influenza and other febrile diseases. Only limited data on the differences in clinical and laboratory parameters between influenza and non-influenza febrile diseases are available to date. METHODS: This was a retrospective case-negative control series that was conducted in Styria, southeast Austria. We analyzed the differences in clinical presentation and laboratory admission parameters between patients with PCR-confirmed H1N1 influenza infection (n = 199) and those with influenza-like disease and negative influenza PCR results (ILD group; n = 252). RESULTS: In the multivariable analysis lower C-reactive protein (CRP) level, lower white blood cell (WBC) count, fever, wheezing, cough, and the absence of nausea or sudden onset remained significant predictors of H1N1 influenza in adult patients (n = 263). Lower CRP level, lower WBC count, and cough remained significant predictors in pediatric patients (<16 years; n = 188). CONCLUSION: Lower CRP level, lower WBC count, and cough were significant predictors of H1N1 in both the adult and pediatric patient group. These data may help to develop an improved case definition for suspected H1N1 infection which combines clinical findings and easily available laboratory parameters.

Procalcitonin fails to predict bacteremia in SIRS patients: a cohort study.

BACKGROUND: Procalcitonin (PCT) has previously been proposed as useful marker to rule out bloodstream-infection (BSI). The objective of this study was to evaluate the sensitivity of different PCT cut-offs for prediction of BSI in patients with community (CA)- and hospital-acquired (HA)-BSI. METHODS: A total of 898 patients fulfilling systemic-inflammatory-response-syndrome (SIRS) criteria were enrolled in this prospective cohort study at the Medical University of Graz, Austria. Of those 666 patients had positive blood cultures (282 CA-BSI, 384 HA-BSI, enrolled between January 2011 and December 2012) and 232 negative blood cultures (enrolled between January 2011 and July 2011 at the emergency department). Blood samples for determination of laboratory infection markers (e.g. PCT) were collected simultaneously with blood cultures. RESULTS: Procalcitonin was significantly (p < 0.001) higher in SIRS patients with bacteremia/fungemia than in those without. Receiver operating characteristic curve analysis revealed an area under the curve (AUC) value of 0.675 for PCT (95% CI 0.636-0.714) for differentiating patients with BSI from those without. AUC for IL-6 was 0.558 (95% CI 0.515-0.600). However, even at the lowest cut-off evaluated (i.e. 0.1 ng/ml) PCT failed to predict BSI in 7% (n = 46) of patients. In the group of patients with SIRS and negative blood culture 79% (n = 185) had PCT levels > 0.1. CONCLUSION: Procalcitonin was significantly higher in patients with BSI than in those without and superior to IL-6 and CRP. The clinical importance of this is questionable, because a suitable PCT threshold for excluding BSI was not established. An approach where blood cultures are guided by PCT only can therefore not be recommended.

Laparoscopic approach of inguinal hernia associated with adult cryptorchidism: case series and literature review.

Cryptorchidism is defined as the extra-scrotal position of the testes. It is a common disorder in male children, but rarely in adult patients. The association of cryptorchidism with hernia is a common finding in childhood, but is not frequent in adults or the elderly. Herein, we report a series of three cases (28-, 24-, and 34-year-old men) of adult inguinal hernia combined with cryptorchidism successfully managed by laparoscopic surgery under the same operative view. Laparoscopic transabdominal preperitoneal repair and orchiectomy were performed in all patients. No complications occurred in the postoperative period, and the patients were discharged on the first or second postoperative day. Pathological examination of the specimens revealed atrophic testes without malignancy. No hernia recurrence was observed during follow-up. The laparoscopic approach in the combined pathology of inguinal hernia and cryptorchidism is feasible in adult patients and has multiple advantages in terms of diagnosis and management.

Investigating the prognostic impact of NY-ESO-1 expression and HLA subtypes in metastatic synovial sarcoma.

BACKGROUND: To better understand the importance of the New York esophageal squamous cell carcinoma 1 (NY-ESO-1) and human leukocyte antigen (HLA) subtypes in treatment decision-making, further investigation of their prevalence and prognostic impact among patients with metastatic synovial sarcoma (mSS) is needed. PATIENTS AND METHODS: This was a retrospective clinico-biological cohort study of adults with mSS. Patient data were collected from the French Sarcoma Group NetSARC database and supplemented by electronic medical records. Primary tumor samples were collected and analyzed for NY-ESO-1 expression by immunohistochemistry (IHC) and HLA-A∗02 status by RNA sequencing (RNA-seq). The primary cohort included patients with available primary tumor samples; the impact of a larger sample size was explored by including patients who had either a primary or metastatic sample (termed the exploratory cohort). P values are provided for descriptive purposes. RESULTS: In 92 patients with primary tumor samples, ∼25% (n = 23) were positive for NY-ESO-1 and HLA-A∗02 expression (dual positive). Among 106 patients with IHC data, 61% (n = 65) were NY-ESO-1 positive, and among 94 patients with RNA-seq data, 45% (n = 42) were HLA-A∗02 positive. The median overall survival (OS) for positive versus negative NY-ESO-1 status was 35.3 and 21.7 months, respectively (unadjusted P = 0.0428). We observed no difference in median OS for HLA-A∗02-positive versus -negative and dual-positive patients versus others (both unadjusted P > 0.05). Multivariate analyses of OS showed no prognostic impact for NY-ESO-1 among primary tumor samples and in the exploratory cohort. However, in the latter we observed an association between NY-ESO-1 expression and OS in the first-line (P = 0.0041) but not in the second-line setting. CONCLUSIONS: The primary tumor cohort showed no association between NY-ESO-1 expression and OS (including stratification by HLA-A∗02 subtype and treatment line) when adjusting for important prognostic factors, possibly due to small sample sizes.

Sclerosing Epithelioid Fibrosarcoma (SEF) versus Low Grade Fibromyxoid Sarcoma (LGFMS): Presentation and outcome in the nationwide NETSARC+ series of 330 patients over 13 years.

Sclerosing Epithelioid Fibrosarcoma (SEF) and Low Grade Fibromyxoid Sarcoma (LGFMS) are ultrarare sarcomas sharing common translocations whose natural history are not well known. We report on the nationwide exhaustive series of 330 patients with SEF or LGFMS in NETSARC+ since 2010. PATIENTS AND METHODS: NETSARC (netsarc.org) is a network of 26 reference sarcoma centers with specialized multidisciplinary tumor boards (MDTB). Since 2010, (i) pathological review has been mandatory for sarcoma,and (ii) tumour/patients' characteristics have been collected in the NETSARC+ nationwide database. The characteristics of patients with SEF and LGFMS and their outcome are compared. RESULTS: 35/73 (48%) and 125/257(49%) of patients with SEF and LGFMS were female. More visceral, bone and trunk primary sites were observed in SEF (p < 0.001). 30% of SEF vs 4% of LGFMS patients had metastasis at diagnosis (p < 0.0001). Median size of the primary tumor was 51 mm (range 10-90) for LGFMS vs 80 (20-320) for SEF (p < 0.001). Median age for LGFMS patients was 12 years younger than that of SEF patients (43 [range 4-98] vs 55 [range 10-91], p < 0.001). Neoadjuvant treatment was more often given to SEF (16% vs 9%, p = 0.05). More patients with LGFMS were operated first in reference centers (51% vs 26%, p < 0.001). The R0 rate on the operative specimen was 41% in LGFMS vs 16% in SEF (p < 0.001). Median event-free survival (EFS) of patients with SEF and LGFMS were 32 vs 136 months (p < 0.0001). The median overall survival (OS) was not reached. Fifty-months OS was 93% vs 81% for LGFMS vs SEF (p = 0.05). Median OS was 77 months after first relapse, similar for SEF and LGFMS. In multivariate analysis, age, tumor size, metastasis at diagnosis were independent prognostic factors for OS in LGFMS. CONCLUSIONS: Although sharing close molecular alterations, SEF and LGFMS have a different natural history, clinical presentation and outcome, with a higher risk of metastatic relapse in SEF. Survival after relapse is longer than with other sarcomas, and similar for SEF and LGFMS.

Sorafenib in patients with progressive malignant solitary fibrous tumors: a subgroup analysis from a phase II study of the French Sarcoma Group (GSF/GETO).

Malignant solitary fibrous tumors are rare soft-tissue sarcomas. They are considered as low-grade malignancies, but may display metastatic potential in 20% of the cases. In case of metastatic or locally advanced, unresectable disease, standard treatments, like anthracycline-based regimens, are poorly effective. Previous studies suggested that antiangiogenic drugs, such as sorafenib, could be efficient to treat vascular sarcomas and solitary fibrous tumors. Five patients with progressive SFT were included in this phase 2 study, and treated with sorafenib at a dose of 800 mg daily. Two patients out of the five achieved a 9 months disease control with sorafenib, while their disease had progressed within the month preceding their inclusion. Consequently, our data suggest a potential efficacy of sorafenib in SFT, Further investigation is needed to confirm these data.

Which lumen is the source of catheter-related bloodstream infection in patients with multi-lumen central venous catheters?

PURPOSE: Paired blood cultures, drawn from the catheter and a peripheral vein, used for calculation of the differential time to positivity (DTP), have been proposed for the detection of catheter-related bloodstream infections (CRBSIs). The most relevant catheter lumen to be sampled in multi-lumen central venous catheters (CVCs) has not been recommended. METHODS: Forty-four febrile neutropaenic patients, following haematopoietic stem cell transplantation (HSCT) and with multi-lumen CVCs in place, were investigated using the DTP method of blood samples drawn from every lumen of the CVC and a peripheral vein. RESULTS: Twelve of 44 patients (27 %) had CRBSIs, as determined by the DTP method. In 10 of 12 (83 %) febrile neutropaenic patients, after HSCT, CRBSIs originated from the CVC lumen used for parenteral nutrition and blood products only. 17 % had CRBSI originating from the other CVC lumen (p = 0.039). CONCLUSION: In most patients, CRBSIs originated from the CVC lumen used for parenteral nutrition and blood products, indicating that this lumen is the main source of CRBSI. However, since 17 % of patients had CRBSIs originating from another lumen, each lumen of multi-lumen CVCs has to be considered as a potential source of CRBSI and should, ideally, be sampled in order to avoid failure in diagnostic procedures.

Successful management of nosocomial ventriculitis and meningitis caused by extensively drug-resistant Acinetobacter baumannii in Austria.

Nosocomial infections caused by the Gram-negative coccobacillus Acinetobacter baumannii have substantially increased over recent years. Because Acinetobacter is a genus with a tendency to quickly develop resistance to multiple antimicrobial agents, therapy is often complicated, requiring the return to previously used drugs. The authors report a case of meningitis due to extensively drug-resistant A baumannii in an Austrian patient who had undergone neurosurgery in northern Italy. The case illustrates the limits of therapeutic options in central nervous system infections caused by extensively drug-resistant pathogens.

Les infections d'origine nosocomiale causées par le coccobacille Acinetobacter baumannii Gram négatif ont considérablement augmenté ces dernières années. Puisque l'Acinetobacter est un genre qui a tendance à devenir rapidement résistant à de multiples agents antimicrobiens, le traitement est souvent compliqué et exige de revenir à des médicaments déjà utilisés. Les auteurs signalent un cas de méningite attribuable à un A baumannii d'une extrême résistance aux médicaments chez un patient autrichien qui a subi une neurochirurgie dans le nord de l'Italie. Le cas illustre les limites des options thérapeutiques aux infections du système nerveux central causées par des pathogènes d'une extrême résistance aux médicaments.

Eastern Canadian Colorectal Cancer Consensus Conference: standards of care for the treatment of patients with rectal, pancreatic, and gastrointestinal stromal tumours and pancreatic neuroendocrine tumours.

The annual Eastern Canadian Colorectal Cancer Consensus Conference was held in Halifax, Nova Scotia, October 20-22, 2011. Health care professionals involved in the care of patients with colorectal cancer participated in presentation and discussion sessions for the purposes of developing the recommendations presented here. This consensus statement addresses current issues in the management of rectal cancer, including pathology reporting, neoadjuvant systemic and radiation therapy, surgical techniques, and palliative care of rectal cancer patients. Other topics discussed include multidisciplinary cancer conferences, treatment of gastrointestinal stromal tumours and pancreatic neuroendocrine tumours, the use of folfirinox in pancreatic cancer, and treatment of stage ii colon cancer.

Comparative re-analysis evaluation of the Fukushima accident atmospheric radioactive emissions.

In this paper, two decision support systems have been used to re-analyze the Fukushima accident emissions: the European Realtime Online Decision Support System for Nuclear Emergency Management (RODOS, version JRodos 2019)-providing a set of modules for the dispersion of nuclides following atmospheric and aquatic releases, dosimetry modules for dose estimation to individuals and communities for all exposure pathways with application of countermeasures, and modules for time estimation of the radiological situation in inhabited and agricultural areas-and CBRNE Platform, developed by IFIN-HH within a research project on anticipative and prognostic evaluation of chemical, biological, radiological, nuclear and explosive events (CBRNE), which is a tool for effect diagnosis functions, response measures and consecutive recommendation for a large variety of scenarios. We have reproduced the event on both systems, using accident time weather data and updated source terms. Current and initial results were cross-compared and evaluated.

Epithelioid hemangio-endothelioma (EHE) in NETSARC: The nationwide series of 267 patients over 12 years.

EPITHELIOID HEMANGIOENDOTHELIOMA: A NATIONWIDE STUDY: Epithelioid hemangioendothelioma (EHE) is an ultrarare sarcoma whose natural history and treatment is not well defined. We report on the presentation and outcome of 267 patients with EHE in the NETSARC+ network since 2010 in France. PATIENTS AND METHODS: NETSARC (netsarc.org) is a network of 26 reference sarcoma centres with specialised multidisciplinary tumour boards (MDTB), funded by the French National Cancer Institute (NCI), Institut National du Cancer (INCA). Since 2010, presentation to an MDTB and second pathological review are mandatory for sarcoma patients. Patients' characteristics are collected in a nationwide database regularly monitored with stable incidence since 2013. The characteristics of patients with EHE at diagnosis are presented as well as progression-free survival (PFS), overall survival (OS), and outcome under treatment. RESULTS: Two hundred and sixty-seven patients with EHE were included in the NETSARC+ database since 2010. Median age in the series was 51 (range 10-90) years, 58% were women. Median tumour size was 37 mm (4-220). Forty-eight percent, 42%, and 10% were visceral, soft parts, or bone primaries. The most frequent sites were liver (28%), lung (13%). 40% were reported to have systemic (i.e. multifocal or metastatic disease) at diagnosis. With a median follow-up of 20 months, OS and PFS rates at 24 months were 82% and 67%, with 10-year projected OS and PFS of 62% and 21% respectively. Male and M+ patients at diagnosis had a significantly worse OS, but not PFS. Local treatment was associated with a favourable survival in localised but not in patients with advanced stage at diagnosis. For 23 patients receiving medical treatment, PFS and OS were 50.2% and 33.2% at 60 months were respectively. CONCLUSIONS: EHE is a frequently metastatic sarcoma at diagnosis with a unique natural history. This study shows in a nationwide series over 12 years that most patients progressed but are still alive at 10 years, both in localised and metastatic stages.

Forest fragmentation genetics in a formerly widespread island endemic tree: Vateriopsis seychellarum (Dipterocarpaceae).

Habitat fragmentation and changed land use have seriously reduced population size in many tropical forest tree species. Formerly widespread species with limited gene flow may be particularly vulnerable to the negative genetic effects of forest fragmentation and small population size. Vateriopsis seychellarum (Dipterocarpaceae) is a formerly widespread canopy tree of the Seychelles, but is now reduced to 132 adult individuals distributed in eleven sites. Using ten microsatellite loci, a genetic inventory of all adult trees and a sample of 317 progeny, we demonstrate that despite its restricted range, overall genetic diversity was relatively high (H(E) : 0.56). The juvenile cohort, however, had significantly lower allelic richness (adults R(S) : 3.91; juveniles R(S) : 2.83) and observed heterozygosity than adult trees (adults H(O) : 0.62; juveniles H(O) : 0.48). Rare alleles were fewer and kinship between individuals was stronger in juveniles. Significant fine-scale spatial genetic structure was observed in remnant adults, and parentage analysis indicated that more than 90% of sampled progeny disperse <25 m and pollen dispersed <50 m. The molecular data confirmed that two populations were derived entirely from self-fertilized offspring from a single surviving mother tree. These populations produce viable offspring. Despite this extreme genetic bottleneck, self-compatibility may provide V. seychellarum with some resistance to the genetic consequences of habitat fragmentation, at least in the short term. We discuss our findings in the context of other rare and threatened dipterocarp species which are vulnerable to miss-management of genetic resources and population fragmentation.

Back from the brink: potential for genetic rescue in a critically endangered tree.

Rare plant species are vulnerable to genetic erosion and inbreeding associated with small population size and isolation due to increasing habitat fragmentation. The degree to which these problems undermine population viability remains debated. We explore genetic and reproductive processes in the critically endangered long-lived tropical tree Medusagyne oppositifolia, an endemic to the Seychelles with a naturally patchy distribution. This species is failing to recruit in three of its four populations. We evaluate whether recruitment failure is linked to genetic problems associated with fragmentation, and if genetic rescue can mitigate such problems. Medusagyne oppositifolia comprises 90 extant trees in four populations, with only the largest (78 trees) having successful recruitment. Using 10 microsatellite loci, we demonstrated that genetic diversity is high (H(E) : 0.48-0.63; H(O) : 0.56-0.78) in three populations, with only the smallest population having relatively low diversity (H(E) : 0.26 and H(O) : 0.30). All populations have unique alleles, high genetic differentiation, and significant within population structure. Pollen and seed dispersal distances were mostly less than 100 m. Individuals in small populations were more related than individuals in the large population, thus inbreeding might explain recruitment failure in small populations. Indeed, inter-population pollination crosses from the large donor population to a small recipient population resulted in higher reproductive success relative to within-population crosses. Our study highlights the importance of maintaining gene flow between populations even in species that have naturally patchy distributions. We demonstrate the potential for genetic and ecological rescue to support conservation of plant species with limited gene flow.