[Blue toe syndrome as an initial manifestation of metastatic prostate cancer : A case report with literature review]. / Un syndrome des orteils bleus révélant un cancer de la prostate métastatique : une observation avec analyse de la littérature.

INTRODUCTION: Cutaneous and vascular manifestations of cancer are numerous. Among paraneoplastic acral vascular syndrome, we report a case of blue toe syndrome as the first manifestation of a prostate cancer following with analysis of this syndrome according literature. OBSERVATION: A 56-year-old man, with Raynaud's phenomenon of the upper limbs for 2 to 3 years, had 4 blue toes of the left foot evolving for 18 months, without ulceration, the pulses being present. Vascular and cardiac explorations (ultrasound, angio-MRI) were normal. There was no biological or immunological abnormality except an elevated PSA level. Prostate biopsies confirmed diagnosis and abdomino-pelvic CT scan proved the bone and lymph node metastasis. CONCLUSION: The revelation of a prostate cancer with bone metastases by a blue toe syndrome is a rare situation. In a patient with a blue toe syndrome with no obvious clinical or biological abnormality, especially atheromatous, investigations should include a search for cancer, which can be revealed by blue toes.

[Puffy hand syndrome: A little-known diagnosis]. / Le syndrome des grosses mains : un diagnostic méconnu.

INTRODUCTION: Puffy hand syndrome is a rare complication of intravenous drug addiction. Diagnosis is based on the patient's history and clinical examination. OBSERVATIONS: A woman and two men, aged 42, 39 and 36 years old, are described. All had a history of intravenous drug use of heroin and oral buprenorphine misuse. Puffy hand syndrome appeared during drug addiction (n = 2) or after its withdrawal (n = 1). It was associated with acrocyanosis (n = 1) or injection scars (n = 1). Upper limb ultrasonography showed sequelae of venous (n = 3) or arterial (n = 1) thrombosis. An upper limb lymphoscintigraphy in one patient showed decreased radionuclide uptake of axillary lymph node and subdermal reflux tracer in the forearm. Treatment was based on low-stretch bandages to reduce the volume and then elastic compression sleeve for long-term stabilization. CONCLUSION: Puffy hand syndrome seen in intravenous drug addicts is poorly understood. It is a chronic complication despite the cessation of drug use. This syndrome has to become more widely known because its management is mandatory, although symptomatic.

[Lower limb lymphedema: A rare manifestation of spondyloarthropathy]. / Lymphœdème des membres inférieurs : une manifestation rare des spondyloarthrites.

INTRODUCTION: Spondyloarthritis include articular (axial, peripheral or enthesitic) and extra-articular manifestations. We reported three cases of limb lymphedema associated with a spondyloarthritis. CASE REPORTS: We report on two men and one female aged of 75, 52 and 39 years, respectively. The rheumatic disease was an ankylosing spondylitis HLA B27 positive in two patients and a psoriatic arthritis in the remaining one. Lymphedema, always unilateral, confirmed by the Stemmer's sign, involved the whole lower limb (n=2) or only the foot and calf (n=1). Lymphedema occurred 3 months, 40 and 9 years after the onset of spondyloarthritis. Lower limb lymphoscintigraphy was abnormal in all cases: decrease (n=2) or absence (n=1) of inguinal lymph node uptake, and visualization of the popliteal lymph node related to deep lymphatic pathway (n=1). Treatment of the spondyloarthritis did not improve lymphedema. Both the low-stretch bandage and elastic compression treatment allowed its reduction and stabilization. CONCLUSION: Limb lymphedema is a rare extra-articular manifestation of spondyloarthritis. Its course appears to be independent of joint disease. Its management is specific and should be associated to that of the rheumatologic disorder.

[Lymphedema in patients treated with sirolimus: 15 cases]. / Lymphœdèmes associés à la prise de sirolimus : à propos de 15 patients.

BACKGROUND: Sirolimus is a mammalian target of rapamycin (mTOR) inhibitor used after organ transplantation and to treat vascular malformations. Among its adverse effects, limb lymphedema has been described. OBJECTIVE: The aim of this study was to analyze the clinical features, lymphoscintigraphy and lymphedema outcome in patients treated with sirolimus. PATIENTS AND METHODS: Monocentric retrospective study from January 2008 to September 2017 analyzing all consecutive patients having lymphedema occurring with sirolimus. RESULTS: Fifteen patients (7 men, 8 women), mean age at the first visit, 56 years (range: 38-76), had a kidney transplant (n=12), liver transplant (n=1), or lymphangioleiomyomatosis (n=2) treated with sirolimus at a mean daily dose of 1.8mg were included. Lymphedema involved one (n=4), or both (n=1) lower limbs, upper limb (n=9), lower limbs and upper limb (n=1). Lymphedema affected the whole limb (n=10), or the distal part (n=5). The median time between lymphedema onset and the beginning of sirolimus was 52 weeks (range: 8-232). Lymphoscintigraphy in 7 patients (lower limb: 3, superior: 4) showed no inguinal or axillary nodal fixation (n=6) or decreased uptake (n=1). Sirolimus was discontinued in 7 cases without lymphedema improvement with a median follow-up of 12 months and maintained in 8 cases. CONCLUSION: Sirolimus is associated with upper and/or lower limb lymphedema, without predominance of sex, and without disappearance after sirolimus discontinuation. Pathophysiological mechanisms remain unclear. Lymphedema management is based on low-stretch bandages and compression.

Interest of punch skin grafting for the treatment of painful ulcers.

UNLABELLED: Skin leg ulcers are chronic painful wounds. The treatment of these ulcers is crucial for patients because pain has a significant impact on their daily lives. The analgesic effect of punch skin grafting (PSG) for the treatment of painful ulcers is not well described. The objective of the study is to assess the level of pain in patients with an ulcerated wound and to see if there is an analgesic effect of PSG. PATIENT AND METHODS: A single-center, non-interventional study conducted in hospitalized patients with one or several ulcer(s) of any type and which has been painful for more than six weeks. Pain was assessed before, the day after a PSG and then on the way out of hospital by a questionnaire and a numeric pain rating scale. Permanent pain and pain peaks were identified. RESULTS: Forty-one patients were included (23 men and 18 women) with a mean age of 73±21 years, 36% (n=15) with arterial ulcers, 36% (n=15) with venous ulcers, 12% (n=5) with necrotic angiodermatitis, 12% (n=5) with mixed ulcers and 4% (n=2) with "other ulcers" (due to infection and use of hydroxycarbamide). On day 1 of PSG, patients showed an improvement in terms of permanent pain (77%, n=24/31) and pain peaks (90%, n=37/41) respectively and 90% (n=28/31) and 95% (n=39/41) on the last day at hospital. Reduction in the use of strong opioids was found in 13 patients (81%). CONCLUSION: Punch skin grafting is a simple and validated treatment, which can reduce or eliminate pain related to ulcers. It has an effect on permanent pain and pain peaks. Its efficiency is particularly demonstrated on venous ulcers and mixed ulcers but also initially painful ulcers such as necrotic angiodermatitis or arterial ulcers.

[Interest of punch skin grafting for the treatment of painful ulcers]. / Intérêt de la greffe cutanée en pastilles dans la prise en charge d'ulcères algiques.

INTRODUCTION: Skin leg ulcers are chronic painful wounds. The treatment of these ulcers is crucial for patients because pain has a significant impact on their daily lives. The analgesic effect of punch skin grafting (PSG) for the treatment of painful ulcers is not well described. The objective of the study is to assess the level of pain in patients with an ulcerated wound and to see if there is an analgesic effect of PSG. PATIENT AND METHODS: It was a single-center, non-interventional study conducted in hospitalized patients with one or several ulcer(s) of any type and which has been painful for more than six weeks. Pain was assessed before, the day after a PSG and then on the way out of hospital by a questionnaire and a numeric pain rating scale. Permanent pain and pain peaks were identified. RESULTS: Forty one patients were included (23 men and 18 women) with mean age of 73±21 years, 36% (n=15) with arterial ulcers, 36% (n=15) with venous ulcers, 12% (n=5) with necrotic angiodermatitis, 12% (n=5) with mixed ulcers and 4% (n=2) with "other ulcers" (due to infection and use of Hydroxycarbamide). On day 1 of PSG, patients showed an improvement in terms of permanent pain (77%, n=24/31) and pain peaks (90%, n=37/41) respectively and 90% (n=28/31) and 95% (n=39/41) on the last day at hospital. Reduction in the use of strong opioids was found in 13 patients (81%). CONCLUSION: Punch skin grafting is a simple and validated treatment, which can reduce or eliminate pain related to ulcers. It has an effect on permanent pain and pain peaks. Its efficacy is particularly demonstrated on venous ulcers and mixed ulcers but also initially painful ulcers such as necrotic angiodermatitis or arterial ulcers.

PO-13 - Production of a functional thrombopoietin by a human ovarian cancer cell line.

INTRODUCTION: Hemostatic abnormalities are frequently noticed in patients with malignant diseases. These complications include platelets disorders. The role of platelets in cancer extends beyond thrombocytosis and thrombosis, and also platelets promote cancer growth and metastatic dissemination. In the physiology, platelet production is regulated by thrombopoietin, which is mainly secreted by the liver. We, previously, reported that thrombopoietin could be secreted by the ovarian adenocarcinoma cell line, OVCAR-3. AIM: Our main purpose is to analyze the gene expression of thrombopoietin in ovarian cancer cells and to assess its functionality. MATERIALS AND METHODS: The thrombopoietin gene expression in ascitic cells from patients with ovarian carcinomatosis, as well as, in three cancer cell lines, including OVCAR-3 cells, performed using reverse transcription PCR, real-time PCR and gene sequencing, Normal human ovary and liver tissues are used as controls. The functionality of thrombopoietin on the basis of the viability of a thrombopoietin-dependent cell line (Ba/F3) using a co-culture method. RESULTS: Similarly to liver and ovary tissues, all cancer cells lines express the three TPO-1 (full length TPO), TPO-2 (12bp deletion) and TPO-3 (116pb deletion) variants. By flow cytometry, we show that thrombopoietin production by OVCAR-3 could be increased when cells are stimulated by activated protein C. Lastly, Our results confirm that activated protein C may act, in a paracrine fashion, to boost thrombopoietin production. CONCLUSIONS: We report, for the first time, that thrombopoietin secreted by ovarian cancer cells is functional. Hence, thrombopoietin produced by tumor cells may have a direct effect on thrombocytosis/thrombosis occurrence in patients with ovarian cancer.

PO-23 - Expression of heparanase in cancer as biomarker of malignancies: overexpression in an aggressive, poor survival gastric cancer "gastric signet ring cell carcinoma" compared with that of other gastric cancers.

INTRODUCTION: Gastric signet ring cell carcinoma (GSRC) is a distinct entity among of other gastric cancer. With unknown etiopathology, their incidence is increasing and it presents a low sensitivity to chemotherapy. AIM: Here, we studied the expression of the heparanase (HPA) in cancer tissues from GSRC patients and several cancer cell lines. HPA is an endo-ß-D-glucuronidase, capable of cleaving the lateral chains of heparan sulfate on cell surfaces and the extracellular matrix at acidic pH. Apart from its well-characterized enzyme activity, HPA also has independent enzymatic functions, such as up-regulation of vascular endothelial growth factor (VEGF) -A and VEGF-C and activation of intracellular signaling pathways involved in, survival, migration and proliferation of tumor cells. It can also induce an hypercoagulability by a non-enzymatic manner. MATERIALS AND METHODS: HPA was tested in several cancer cell lines from ovaries (OVCAR-3, SKOV-3), breast (MDAMB231, MCF7) colon (LS-174), lung (A549), uterus (HELA) and gastric (adenocarcinoma (AGS) and GSRC (KATO-III) using several techniques such as RT-PCR, Q-PCR, immunocytochemistry, flow cytometry and degradation of Fondaparinux at pH 5, evaluated by its anti Xa activity evaluated by Factor Xa amidolytic activity. The amount of HPA mRNA in the biopsy simples of gastric adenocarcinoma (n=10) and GSRC (n=11) in tumors and their environment were analyzed. RESULTS: HPA gene is expressed in all cancer cell lines, but its level varies depending on the tumor cell line. In biopsies of gastric cancer, the HPA gene is more expressed in the tumor regions (p=0.0002) and tumor environment (p=0.015) in GSRC than in gastric adenocarcinoma. B) The activity of HPA, evaluated by degradation of Fondaparinux at pH 5, 1) in the supernatants of 10(6) cancer cells: the residual activity of Fondaparinux after 2 hours incubation at 37°C with OVCAR-3 supernatant was of 70% of control value, and of 80% with KATO-III cell supernatants. 2) in patient's plasmas, this technique cannot be used because the site of degradation of fondaparinux by heparanase is masked by AT present in plasma. CONCLUSIONS: Heparanase was found in in many cancer cell lines and its level depends on origin of tumor cells and on its aggressivity. Taking into account the pro-metastatic functions, proangiogenic and procoagulant activity of HPA and its overexpression in gastric signet ring cell carcinoma of poor prognosis and its cell line, HPA can be considered as a biomarker of malignancy and as a therapeutic target in GSRC patients.

[Vascular myeloproliferative neoplasm with normal cell blood count: Exploration and medical management]. / Les syndromes myéloprolifératifs d'expression vasculaire à numération normale : comment les explorer ?

UNLABELLED: Negative BCR ABL myeloproliferative neoplasm (MPN) such as polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (MFP) are clonal hematological malignancies and may lead to a high risk of venous, arterial or microcirculatory thrombosis. Atypical sites of thrombosis can sometimes reveal the neoplasm disorder. Their diagnoses are a major issue because of the propensity to develop acute myeloid leukemia and/or myelofibrosis. The acquired JAK2V617F variant (Janus kinase 2; 9p24) is a prevalent MPN and also a sensitive marker for PV diagnosis (95% positive mutation), but not specific since found in approximately 50% of patients with ET and MFP. PATIENT AND METHODS: We present a diagnostic and a therapeutic approach based on one patient with microcirculatory ischemic manifestations in the toes, and who had strictly normal cell blood counts and was positive for JAK2V617F mutation: thrombotic risk factor evaluation; bone marrow biopsy; red cell adhesion assays. These experimental assays are promising for the development of new therapeutics in MPN; they assess red cell adherence to the vascular endothelium after the phosphorylation of Lu/BCAM subsequent to a positive JAK2V617F mutation. RESULTS: Compared with controls, our patient exhibited increased Lu/BCAM receptor phosphorylation and red blood cell adhesion. CONCLUSION: This development may lead to improved care for patients with thrombotic manifestations, normal blood cell counts, and a positive JAK2V617F mutation: multidisciplinary management, including regular hematological monitoring, could lead to the introduction of a cytoreductive treatment.