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A case of a patient suffering from COVID-19 with suspected associated myositis is reported, in which the initially limited information about the history and disease course led to difficulties in establishing a reasonable diagnosis. Through inquiry, further data could be collected, so that the diagnosis of an infection-associated thrombotic microangiopathy in the context of a Morganella morganii myositis could be made. This patient study shows that even in times of the omnipresent pandemic and despite the context of a positive COVID-19 test result, differential diagnoses and the integrative clinicopathologic approach in interpreting muscle biopsy findings should not be neglected.

International audience

Introduction: Sarcomas challenge research and clinical routine standards because of the complex treatment intervention required and the treatment associated burden. Patients report severe limitations in quality of life and currently there is a lack of an interdisciplinary nationwide network for the [for full text, please go to the a.m. URL], 17. Deutscher Kongress für Versorgungsforschung (DKVF)

While they account for one-fifth of new cancer cases, rare cancers are difficult to study. A higher than average degree of uncertainty should be accommodated for clinical as well as for population-based decision making. Rules of rational decision making in conditions of uncertainty should be rigorously followed and would need widely informative clinical trials. In principle, any piece of new evidence would need to be exploited in rare cancers. Methodologies to explicitly weigh and combine all the available evidence should be refined, and the Bayesian logic can be instrumental to this end. Likewise, Bayesian-design trials may help optimize the low number of patients liable to be enrolled in clinical studies on rare cancers, as well as adaptive trials in general, with their inherent potential of flexibility when properly applied. While clinical studies are the mainstay to test hypotheses, the potential of electronic patient records should be exploited to generate new hypotheses, to create external controls for future studies (when internal controls are unpractical), to study effectiveness of new treatments in real conditions. Framework study protocols in specific rare cancers to stepwisely test sets of new agents, as from the early post-phase I development stage, should be encouraged. Also the compassionate and the off-label settings should be exploited to generate new evidence, and flexible regulatory innovations such as adaptive licensing could convey new agents early to rare cancer patients, while generating evidence. Though validation of surrogate end points is problematic in rare cancers, the use of an updated notion of tumor response may be of great value in the single patient to optimize the use of therapies, all the more the new ones. Disease-based communities, involving clinicians and patients, should be regularly consulted by regulatory bodies when setting their policies on drug approval and reimbursement in specific rare cancers ., While they account for one-fifth of new cancer cases, rare cancers are difficult to study. A higher than average degree of uncertainty should be accommodated for clinical as well as for population-based decision making. Rules of rational decision making in conditions of uncertainty should be rigorously followed and would need widely informative clinical trials. In principle, any piece of new evidence would need to be exploited in rare cancers. Methodologies to explicitly weigh and combine all the available evidence should be refined, and the Bayesian logic can be instrumental to this end. Likewise, Bayesian-design trials may help optimize the low number of patients liable to be enrolled in clinical studies on rare cancers, as well as adaptive trials in general, with their inherent potential of flexibility when properly applied. While clinical studies are the mainstay to test hypotheses, the potential of electronic patient records should be exploited to generate new hypotheses, to create external controls for future studies (when internal controls are unpractical), to study effectiveness of new treatments in real conditions. Framework study protocols in specific rare cancers to sequentially test sets of new agents, as from the early post-phase I development stage, should be encouraged. Also the compassionate and the off-label settings should be exploited to generate new evidence, and flexible regulatory innovations such as adaptive licensing could convey new agents early to rare cancer patients, while generating evidence. Though validation of surrogate end points is problematic in rare cancers, the use of an updated notion of tumor response may be of great value in the single patient to optimize the use of therapies, all the more the new ones. Disease-based communities, involving clinicians and patients, should be regularly consulted by regulatory bodies when setting their policies on drug approval and reimbursement in specific rare cancers.

Kaposi sarcoma (KS) is a virus-related malignancy which most frequently arises in skin, though visceral sites can also be involved. Infection with Kaposi sarcoma herpes virus (KSHV or HHV-8) is required for development of KS. Nowadays, most cases worldwide occur in persons who are immunosuppressed, usually because of HIV infection or as a result of therapy to combat rejection of a transplanted organ, but classic Kaposi sarcoma is predominantly a disease of the elderly without apparent immunosuppression. We analyzed 2667 KS incident cases diagnosed during 1995-2002 and registered by 75 population-based European cancer registries contributing to the RARECARE project. Total crude and age-standardized incidence rate was 0.3 per 100,000 per year with an estimated 1642 new cases per year in the EU27 countries. Age-standardized incidence rate was 0.8 per 100,000 in Southern Europe but below 0.3 per 100,000 in all other regions. The elevated rate in southern Europe was attributable to a combination of classic Kaposi sarcoma in some Mediterranean countries and the relatively high incidence of AIDS in several countries. Five-year relative survival for 2000-2002 by the period method was 75%. More than 10,000 persons were estimated to be alive in Europe at the beginning of 2008 with a past diagnosis of KS. The aetiological link with suppressed immunity means that many people alive following diagnosis of KS suffer comorbidity from a pre-existing condition. While KS is a rare cancer, it has a relatively good prognosis and so the number of people affected by it is quite large. Thus it provides a notable example of the importance of networking in diagnosis, therapy and research for rare cancers.

Sarcomas are a heterogeneous group of malignant neoplasms arising from mesenchymal cells which encompass dozens of histological types and can occur in virtually any anatomic site. They form one of the principal groups of rare cancers in Europe as defined in the RARECARE project. We analysed 45,568 incident cases diagnosed during 1995-2002 and registered by 76 population-based cancer registries. Total crude incidence was 5.6 per 100,000 per year with an estimated 27,908 new cases per year in the EU27 countries, of which 84% were soft tissue sarcomas and 14% were bone sarcomas. Gastrointestinal stromal tumours (GIST) were only widely recognised as an entity in the late 1990s and consequently were under-registered. Their true incidence is believed to be about 1.5 per 100,000. Age-standardised incidence of soft tissue sarcomas ranged from 3.3 per 100,000 in Eastern Europe to 4.7 per 100,000 in Northern Europe. About 280,000 persons were estimated to be alive at the beginning of 2003 with a past diagnosis of sarcoma, of which 83% were soft tissue sarcomas and 16% were bone sarcomas. Five-year relative survival for 2000-2002 by the period was 58% for soft tissue sarcomas and 62% for bone sarcomas. The diversity and rarity of sarcomas combined with the quite large number of people affected by them mean that they provide a classic example of the importance of networking in diagnosis, therapy and research for rare cancers.

International audience; PURPOSE: Epidemiologic information on rare cancers is scarce. The project Surveillance of Rare Cancers in Europe (RARECARE) provides estimates of the incidence, prevalence and survival of rare cancers in Europe based on a new and comprehensive list of these diseases. MATERIALS AND METHODS: RARECARE analysed population-based cancer registry (CR) data on European patients diagnosed from 1988 to 2002, with vital status information available up to 31st December 2003 (latest date for which most CRs had verified data). The mean population covered was about 162,000,000. Cancer incidence and survival rates for 1995-2002 and prevalence at 1st January 2003 were estimated. RESULTS: Based on the RARECARE definition (incidence

The prognosis of cancer disease is worsened upon shedding of tumor cells from the primary tumor, which escape to the blood stream and form metastases at distant sites within the body. Inhibition of cell shedding from the primary tumor could therefore be exploited to avoid metastasis and delay the progression of the cancer disease. In the present study, we investigated the effects of the polyphenols resveratrol, baicalein, epicatechin, epigallocatechin and polyphenon 60 on cell shedding from multicellular tumor spheroids of the murine mammacarcinoma cell line 4T1, cell invasion into embryonic stem cell-derived tissues, generation of reactive oxygen species (ROS) and expression of matrix metalloproteinase 9 (MMP-9). With increasing tumor spheroid growth MMP-9 expression was upregulated and cells detached from tumor spheroids and formed subspheroids that displayed pronounced ROS generation. Upon incubation with polyphenols tumor growth was arrested and cell shedding was totally abolished. Polyphenol treatment decreased ROS generation and downregulated MMP-9 expression. Furthermore, polyphenols significantly inhibited invasion of tumor cells into embryonic stem cell-derived, vascularized tissues. Our data suggest, that polyphenols inhibit cell shedding and invasion by their anti-oxidative capacity and downregulation of MMP-9 expression.

Cardiomyogenesis in differentiating mouse embryonic stem (ES) cells is promoted by cardiotrophin-1 (CT-1), a member of the IL-6 interleukin superfamily that acts through the tall gp130 cytokine receptor. We show that prooxidants (menadione, hydrogen peroxide) as well as chemical (CoCl2) and physiological (1% O2) hypoxia increased CT-1 as well as HIF-1{alpha} protein and mRNA expression in embryoid bodies, indicating that CT-1 expression is regulated by reactive oxygen species (ROS) and hypoxia. Treatment with either prooxidants or chemical hypoxia increased gp130 phosphorylation and protein expression of NADPH oxidase subunits p22-phox, p47-phox, p67-phox, as well as Nox1 and Nox4 mRNA. Consequently, inhibition of NADPH oxidase activity by diphenylen iodonium chloride (DPI) and apocynin abolished prooxidant- and chemical hypoxia-induced upregulation of CT-1. Prooxidants and chemical hypoxia activated ERK1,2, JNK and p38 as well as PI3-kinase. The proxidant- and CoCl2-mediated upregulation of CT-1 was significantly inhibited in the presence of the ERK1,2 antagonist UO126, the JNK antagonist SP600125, the p38 antagonist SKF86002, the PI3-kinase antagonist LY294002, the Jak-2 antagonist AG490 as well as in the presence of free radical scavengers. Moreover, developing embryoid bodies derived from HIF-1{alpha}-/- ES cells lack cardiomyogenesis, and prooxidants as well as chemical hypoxia failed to upregulate CT-1 expression. Our results demonstrate that CT-1 expression in ES cells is regulated by ROS and HIF-1{alpha} and imply a crucial role of CT-1 in the survival and proliferation of ES-cell-derived cardiac cells.