Myeloid cells contribute to tumor lymphangiogenesis.

The formation of new blood vessels (angiogenesis) and lymphatic vessels (lymphangiogenesis) promotes tumor outgrowth and metastasis. Previously, it has been demonstrated that bone marrow-derived cells (BMDC) can contribute to tumor angiogenesis. However, the role of BMDC in lymphangiogenesis has largely remained elusive. Here, we demonstrate by bone marrow transplantation/reconstitution and genetic lineage-tracing experiments that BMDC integrate into tumor-associated lymphatic vessels in the Rip1Tag2 mouse model of insulinoma and in the TRAMP-C1 prostate cancer transplantation model, and that the integrated BMDC originate from the myelomonocytic lineage. Conversely, pharmacological depletion of tumor-associated macrophages reduces lymphangiogenesis. No cell fusion events are detected by genetic tracing experiments. Rather, the phenotypical conversion of myeloid cells into lymphatic endothelial cells and their integration into lymphatic structures is recapitulated in two in vitro tube formation assays and is dependent on fibroblast growth factor-mediated signaling. Together, the results reveal that myeloid cells can contribute to tumor-associated lymphatic vessels, thus extending the findings on the previously reported role of hematopoietic cells in lymphatic vessel formation.

Concepts of metastasis in flux: the stromal progression model.

The ability of tumor cells to leave a primary tumor, to disseminate through the body, and to ultimately seed new secondary tumors is universally agreed to be the basis for metastasis formation. An accurate description of the cellular and molecular mechanisms that underlie this multistep process would greatly facilitate the rational development of therapies that effectively allow metastatic disease to be controlled and treated. A number of disparate and sometimes conflicting hypotheses and models have been suggested to explain various aspects of the process, and no single concept explains the mechanism of metastasis in its entirety or encompasses all observations and experimental findings. The exciting progress made in metastasis research in recent years has refined existing ideas, as well as giving rise to new ones. In this review we survey some of the main theories that currently exist in the field, and show that significant convergence is emerging, allowing a synthesis of several models to give a more comprehensive overview of the process of metastasis. As a result we postulate a stromal progression model of metastasis. In this model, progressive modification of the tumor microenvironment is equally as important as genetic and epigenetic changes in tumor cells during primary tumor progression. Mutual regulatory interactions between stroma and tumor cells modify the stemness of the cells that drive tumor growth, in a manner that involves epithelial-mesenchymal and mesenchymal-epithelial-like transitions. Similar interactions need to be recapitulated at secondary sites for metastases to grow. Early disseminating tumor cells can progress at the secondary site in parallel to the primary tumor, both in terms of genetic changes, as well as progressive development of a metastatic stroma. Although this model brings together many ideas in the field, there remain nevertheless a number of major open questions, underscoring the need for further research to fully understand metastasis, and thereby identify new and effective ways of treating metastatic disease.

Value of sTREM-1, procalcitonin and CRP as laboratory parameters for postmortem diagnosis of sepsis.

OBJECTIVES: Triggering receptor expressed on myeloid cells-1 (TREM-1) was reported to be up-regulated in various inflammatory diseases as well as in bacterial sepsis. Increased cell-surface TREM-1 expression was also shown to result in marked plasma elevation of the soluble form of this molecule (sTREM-1) in patients with bacterial infections. In this study, we investigated sTREM-1, procalcitonin and C-reactive protein in postmortem serum in a series of sepsis-related fatalities and control individuals who underwent medico-legal investigations. sTREM-1 was also measured in pericardial fluid and urine. METHODS: Two study groups were prospectively formed, a sepsis-related fatalities group and a control group. The sepsis-related fatalities group consisted of sixteen forensic autopsy cases. Eight of these had a documented clinical diagnosis of sepsis in vivo. The control group consisted of sixteen forensic autopsy cases with various causes of death. RESULTS: Postmortem serum sTREM-1 concentrations were higher in the sepsis group with a mean value of 173.6 pg/ml in septic cases and 79.2 pg/ml in control individuals. The cutoff value of 90 pg/ml provided the best sensitivity and specificity. Pericardial fluid sTREM-1 values were higher in the septic group, with a mean value of 296.7 pg/ml in septic cases and 100.9 pg/ml in control individuals. The cutoff value of 135 pg/ml provided the best sensitivity and specificity. Mean urine sTREM-1 concentration was 102.9 pg/ml in septic cases and 89.3 pg/ml in control individuals. CONCLUSIONS: Postmortem serum sTREM-1, individually considered, did not provide better sensitivity and specificity than procalcitonin in detecting sepsis. However, simultaneous assessment of procalcitonin and sTREM-1 in postmortem serum can be of help in clarifying contradictory postmortem findings. sTREM-1 determination in pericardial fluid can be an alternative to postmortem serum in those situations in which biochemical analyses are required and blood collected during autopsy proves insufficient.

EORTC-ROG expert opinion: radiotherapy volume and treatment guidelines for neoadjuvant radiation of adenocarcinomas of the gastroesophageal junction and the stomach.

PURPOSE: The Gastro-Intestinal Working Party of the EORTC Radiation Oncology Group (GIWP-ROG) developed guidelines for target volume definition in neoadjuvant radiation of adenocarcinomas of the gastroesophageal junction (GEJ) and the stomach. METHODS AND MATERIALS: Guidelines about the definition of the clinical target volume (CTV) are based on a systematic literature review of the location and frequency of local recurrences and lymph node involvement in adenocarcinomas of the GEJ and the stomach. Therefore, MEDLINE was searched up to August 2008. Guidelines concerning prescription, planning and treatment delivery are based on a consensus between the members of the GIWP-ROG. RESULTS: In order to support a curative resection of GEJ and gastric cancer, an individualized preoperative treatment volume based on tumour location has to include the primary tumour and the draining regional lymph nodes area. Therefore we recommend to use the 2nd English Edition of the Japanese Classification of Gastric Carcinoma of the Japanese Gastric Cancer Association which developed the concept of assigning tumours of the GEJ and the stomach to anatomically defined sub-sites corresponding respectively to a distinct lymphatic spread pattern. CONCLUSION: The GIWP-ROG defined guidelines for preoperative irradiation of adenocarcinomas of the GEJ and the stomach to reduce variability in the framework of future clinical trials.

Diagnostic de la maladie coronarienne stable par FFR non invasive, mythe ou réalité [Diagnosis of stable coronary artery disease with non-invasive FFR: myth or reality?].

Decision to revascularize a patient with stable coronary artery disease should be based on the detection of myocardial ischemia. If this decision can be straightforward with significant stenosis or in non-significant stenosis, the decision with intermediate stenosis is far more difficult and require invasive measures of functional impact of coronary stenosis on maximal blood (flow fractional flow reserve=FFR). A recent computer based method has been developed and is able to measure FFR with data acquired during a standard coronary CT-scan (FFRcT). Two recent clinical studies (DeFACTO and DISCOVER-FLOW) show that diagnostic performance of FFRcT was associated with improved diagnostic accuracy versus standard coronary CT-scan for the detection of myocardial ischemia although FFRcT need further development.

Hypertension pulmonaire: difficulté diagnostique et intérêt de l'échocardiographie [Pulmonary hypertension: difficult diagnosis and role of echocardiography]

Pulmonary hypertension (PH) is a complex disease leading, in its advance form, to a decreased quality of life and early mortality. In the early stage, non specific signs and symptoms are the rule. The diagnosis is often missed, leaving the patient alone to face the disease and its repercussion on his daily life. This article reviews the main PH causes and predisposing conditions. Signs and symptoms suggesting the diagnosis are reviewed as well as conditions recognised at high risk for the disease. The key role of echocardiography in establishing the diagnosis, assessing PH severity, cardiac repercussions and/or potential aetiologies, is addressed. Finally the importance of a multidisciplinary approach is recommended.

Histoplasma capsulatum var. duboisii infection in a patient with AIDS: rapid diagnosis using polymerase chain reaction-sequencing.

We describe an original case of disseminated infection with Histoplasma capsulatum (Hc) var. duboisii in an African patient with AIDS who migrated to Switzerland. The diagnosis of histoplasmosis was suggested using direct examination of tissues and confirmed in 24 h with a panfungal polymerase chain reaction assay. The variety duboisii of Hc was established using DNA sequencing of the polymorphic genomic region OLE. Molecular tools allow diagnosis of histoplasmosis in 24 h, which is drastically shorter than culture procedures.

Diagnosis and key of the main families and species of South American Coleoptera of forensic importance

The objective of this paper is to provide diagnosis and keys of the families and species, with illustrations of the main groups. A table of all related species recorded from South America is presented, including the substrate in which they were collected and their geographical distribution. The list comprises 221 species included in 15 families, of which 70% of the species are from Brazil. Scarabaeidae is the most diverse family with 121 species, followed by Staphylinidae with 68. Also we provide one database of Coleoptera species associated with carcasses in South America.

Delayed diagnosis of acute ischemic stroke in children - a registry-based study in Switzerland.

QUESTIONS UNDER STUDY/PRINCIPLES: After arterial ischemic stroke (AIS) an early diagnosis helps preserve treatment options that are no longer available later. Paediatric AIS is difficult to diagnose and often the time to diagnosis exceeds the time window of 6 hours defined for thrombolysis in adults. We investigated the delay from the onset of symptoms to AIS diagnosis in children and potential contributing factors. METHODS: We included children with AIS below 16 years from the population-based Swiss Neuropaediatric Stroke Registry (2000-2006). We evaluated the time between initial medical evaluation for stroke signs/symptoms and diagnosis, risk factors, co-morbidities and imaging findings. RESULTS: A total of 91 children (61 boys), with a median age of 5.3 years (range: 0.2-16.2), were included. The time to diagnosis (by neuro-imaging) was <6 hours in 32 (35%), 6-12 hours in 23 (25%), 12-24 hours in 15 (16%) and >24 hours in 21 (23%) children. Of 74 children not hospitalised when the stroke occurred, 42% had adequate outpatient management. Delays in diagnosis were attributed to: parents/caregivers (n = 20), physicians of first referral (n = 5) and tertiary care hospitals (n = 8). A co-morbidity hindered timely diagnosis in eight children. No other factors were associated with delay to diagnosis. A total of 17 children were inpatients at AIS onset. CONCLUSIONS: One-third of children with AIS were diagnosed within six hours. Diagnostic delay was predominately caused by insufficient recognition of stroke symptoms. Increased public and expert awareness and immediate access to diagnostic imaging are essential. The ability of parents/caregivers and health professionals to recognise stroke symptoms in a child needs to be improved.

A new species of Solepyris Azevedo (Hymenoptera, Bethylidae) from Brazil, with amended diagnosis of the genus

Solepyris Azevedo is a rarely collected Neotropical genus. It is differentiated from other Sclerodermini genera by having the fore wing venation with a single large closed cell and currently is monotypic containing S. unicus Azevedo. A second species, Solepyris montuosus, sp. nov., from Brazil is described and illustrated. This new species is diagnosed by having radial vein of the fore wing long. An amended diagnosis of Solepyris unicus Azevedo is included. A key for the two species of Solepyris is provided.

Family physician involvement in cancer care follow-up: the experience of a cohort of patients with lung cancer.

PURPOSE There has been little research describing the involvement of family physicians in the follow up of patients with cancer especially during the primary treatment phase We undertook a prospective longitudinal study of patients with lung cancer to assess their family physician s involvement in their follow up at the different phases of cancer METHODS In 5 hospitals in the province of Quebec Canada patients with a recent diagnosis of lung cancer were surveyed every 3 to 6 months whether they had metastasis or not, for a maximum of 18 months to assess aspects of their family physician s involvement in cancer care RESULTS Of the 395 participating patients 92% had a regular family physician but only 60% had been referred to a specialist by him/her or a colleague for the diagnosis of their lung cancer A majority of patients identified the oncology team or oncologists as mainly responsible for their cancer care throughout their cancer journey except at the advanced phase where a majority attributed this role to their family physician At baseline only 16% of patients perceived a shared care pattern between their family physician and oncologists but this pro portion increased with cancer progression Most patients would have liked their family physician to be more involved in all aspects of cancer care CONCLUSIONS Although patients perceive that the oncology team is the main party responsible for the follow up of their lung cancer they also wish their family physicians to be involved Better communication and collaboration between family physicians and the oncology team are needed to facilitate shared care in cancer follow up

Will endoscopists soon replace pathologists in the diagnosis of (pre-)neoplastic and inflammatory mucosal lesions?

This short review addresses the question whether pathologists will continue to play a central role in the diagnosis of mucosal lesions of the gastrointestinal tract or whether their role will soon be assumed by clinical colleagues equipped with modern high-resolution endoscopes. In order to support the raison d'etre of the pathologist - at least for the time being and the near future - the author lists three arguments, related to (i) the differences in the orientation of the plane of view (histology: perpendicular to the mucosal surface vs. endoscopy: parallel to the mucosal surface), (ii) the advantages of staining and immunostaining tissue sections, and (iii) the possibility to perform deeper sections and to consul with colleagues in the case of difficult diagnoses.

Shorter time to diagnosis and improved stage at presentation in Swiss patients with retinoblastoma treated from 1963 to 2004

Rapport de synthèse : Le rétinoblastome est la tumeur de l'oeil la plus fréquente chez l'enfant. Un diagnostic précoce est important pour sauver le globe oculaire et la survie du patient. Le but de notre étude est de déterminer l'évolution de l'intervalle diagnostique, c'est-à-dire le délai entre les premiers symptômes et la date du diagnostic officiel du rétinoblastome, sur une période de 40 ans en Suisse. Matériel et méthode : Il s'agit d'une étude rétrospective faite sur 139 patients suisses traités pour rétinoblastome durant trois différentes périodes : (1) 1963-1983 ; (2) 1984-1993 ; et (3) 1994-2004. On compare certaines caractéristiques : le sexe du patient, la latéralité de la maladie, les premiers symptômes, leurs observateurs, l'intervalle diagnostique, l'âge au diagnostic, le stade de la maladie, l'histoire familiale. Résultats : 37 patients (26.6%) ont été traités dans la première période ; 44 (31.7%) dans la période 2 et 58 (41.7%) dans la période 3. L'intervalle diagnostique diminue de façon significative de 6.97 mois dans la période 1 à 3.58 dans la période 2 à 2.25 dans la période 3 pour le total des malades. Ceci reste significatif pour les rétinoblastomes unilatéraux. De plus, dans ce même groupe, on observe une diminution significative des stades avancés de la maladie, groupe E selon Murphree (61.5% dans la période 1 ; 46.7% dans la période 2 et 22.2 % dans la période 3). Lorsque la maladie est bilatérale, les mêmes observations se font de façon un peu moins marquée. Il n'y a aucun patient diagnostiqué au stade E de la maladie en présence d'une anamnèse familiale positive. Leucocorie (48.2%) et strabisme (20.1 %) sont les symptômes les plus fréquents durant les 3 périodes. Les seuls facteurs qui influencent significativement le risque d'avoir un stade E de la maladie sont la durée de l'intervalle diagnostic et la période de diagnostic. Conclusion : On constate un progrès dans le diagnostic du rétinoblastome en Suisse, surtout lors de maladie unilatérale. De même, des améliorations sont notées dans la maladie bilatérale mais de façon non significative. Il est donc important de mieux enseigner aux médecins à reconnaître les symptômes oculaires de la maladie et à référer les patients plus tôt aux spécialistes. Abstract : OBECTIVES : Retinoblastoma is the most frequent intraocular malignancy in children. Early diagnosis is essential for globe salvage and patient survival. The aim of our study was to determine how time to diagnosis of retinoblastoma has evolved over a 40-year period in Switzerland. METHOD AND PATIENTS : A retrospective study of 139 Swiss patients with retinoblastoma was performed comparing 3 periods: (1) 1963-1983; (2) 1984-1993; and (3) 1994-2004. Factors taken into account were gender, laterality of retínoblastoma, age at first symptoms, type and first observer of symptoms, time to diagnosis, age at diagnosis, disease stage, and family history. RESULTS : Thirty-seven patients (26.6%) were treated in period 1, 44 (31.7%) in period 2, and S8 (41.7%) in period 3.Overall, the diagnostic interval decreased in a significant way from 6.97 months in period 1 to 3.58 in period 2 and to 2.25 in period 3. When looking separately at unilateral and bilateral disease, the decrease oí the diagnostic interval remained statistically significant in unilateral retinoblastoma; there was also a significant reduction in the number of patients with advanced group E disease (Murphree classification) (61.5% in period 1, 46.7% in period 2, 22.2% in period 3). In bilateral disease, the same observations were made to a lesser extent. However, there were no cases with group E disease in 10 patients with positive family history. Leukornria (48.2%) and strabismus (20.1 %) were the 2 most frequent symptoms throughout the 3 periods. The only factors that statistically influenced the chances of having a diagnosis of group E disease were the diagnostic interval and period of diagnosis. Conclusion : Progress has been made in the diagnosis of retinoblastoma in Switzerland, notably in unilateral disease. Improvement to a lesser extent has also been observed in bilateral cases but without statistical significance. Greater effort is needed to teach physians-in-training to recognize the importance of ocular symptoms and refer patients earlier.