Is E-FAST possible and useful on the battlefield? A feasibility study during medical courses in hostile environment (MEDICHOS): preliminary results.

INTRODUCTION: The extent of the French forces' territory in the Sahel band generates long medical evacuations. In case of many victims, to respect the golden hour rule, first-line sorting is essential. Through simulation situations, the aim of our study was to assess whether the use of ultrasound was useful to military doctors. METHODS: In combat-like exercise conditions, we provided trainees with a pocket-size ultrasound. Every patient for whom the trainees chose to perform ultrasound in role 1 was included. An extended focused assessment with sonography for trauma (E-FAST) was performed with six basic sonographic views. We evaluated whether these reference views were obtained or not. Once obtained by the trainees, pathological views corresponding to the scenario were shown to assess whether the trainees modified their therapeutic management strategy and their priorities. RESULTS: 168 patients were treated by 15 different trainee doctors. Of these 168 patients, ultrasound (E-FAST or point-of-care ultrasound) was performed on 44 (26%) of them. In 51% (n=20/39) of the situations, the practitioners considered that the realisation of ultrasound had a significant impact in terms of therapeutic and evacuation priorities. More specifically, it changed therapeutic decisions in 67% of time (n=26/39) and evacuation priorities in 72% of time (n=28/39). CONCLUSION: This original work showed that ultrasound on the battlefield was possible and useful. To confirm these results, ultrasound needs to be democratised and assessed in a real operational environment.

Antibody targeting of claudin-1 as a potential colorectal cancer therapy.

BACKGROUND: Metastatic colorectal cancer (mCRC) is one of the major causes of cancer-related death. Despite the substantial progress in mCRC management, it remains important to identify new therapeutic options and biological markers for personalized medicine. Here, we investigated the expression of claudin-1 (CLDN1), a major tight junction transmembrane protein, in the different colorectal cancer (CRC) molecular subtypes and then assessed the anti-tumor effect of a new anti-CLDN1 monoclonal antibody (mAb). METHODS: Gene expression profiling and immunochemistry analysis of normal and tumor tissue samples from patients with stage IV CRC were used to determine CLDN1 gene expression. Then, the 6F6 mAb against CLDN1 extracellular part was generated. Its effect on CRC cell cycle, proliferation, survival and migration was assessed in vitro, using a 3D cell culture system, flow cytometry, clonogenic and migration assays. In vivo, 6 F6 mAb efficacy was evaluated in nude mice after subcutaneous xenografts or intrasplenic injection of CRC cells. RESULTS: Compared with normal mucosa where it was almost exclusively cytoplasmic, in CRC samples CLDN1 was overexpressed (p < 0.001) and mainly localized at the membrane. Moreover, it was differentially expressed in the various CRC molecular subtypes. The strongest expressions were found in the consensus molecular subtype CMS2 (p < 0.001), the transit-ampliflying (p < 0.001) and the C5 subtypes (p < 0.001). Lower CLDN1 expression predicted a better outcome in the molecular subtypes C3 and C5 (p = 0.012 and p = 0.004, respectively). CLDN1 targeting with the 6 F6 mAb led to reduction of survival, growth and migration of CLDN1-positive cells. In preclinical mouse models, the 6F6 mAb decreased tumor growth and liver metastasis formation. CONCLUSION: Our data indicate that CLDN1 targeting with an anti-CLDN1 mAb results in decreased growth and survival of CRC cells. This suggests that CLDN1 could be a new potential therapeutic target.

Scabietic vasculitis: Report of 2 cases.

BACKGROUND: The infectious causes of cutaneous vasculitis are well known and include streptococcal infections among others. Cases resulting from parasitic infection are less frequent. Scabies, which is currently on the increase, has only been reported in a few isolated cases. Herein, we report two noteworthy cases of profuse scabies complicated by cutaneous vasculitis. PATIENTS AND METHODS: Case 1: a 90-year-old woman, residing in a nursing home, was admitted to our dermatology department complaining of pruritus, present for one month, predominantly on the inside of the thighs and on the buttocks, associated with purpuric lesions on the lower limbs. A skin biopsy revealed leukocytoclastic vasculitis. A diagnosis of scabies was based on severe pruritus and hypereosinophilia and was confirmed by microscopic examination of the parasitology sample and the skin biopsy sample. Despite thorough investigation, no other cause of vasculitis could be found. Complete regression of the skin lesions was achieved with scabies treatment only, without any specific treatment for the vasculitis. Case 2: a 74-year-old man, living in a nursing home, was hospitalized for purpuric papules on the lower limbs, present for one month. Physical examination revealed linear patterns in the interdigital spaces associated with scabies evident on dermoscopic examination. The skin biopsy revealed signs of vasculitis. As in our first case, no aetiology of vasculitis was found and a favorable outcome was achieved by means of scabies treatment alone with no specific treatment for vasculitis. DISCUSSION: Both of our patients presented scabies and vasculitis. In view of the absence of other causes of vasculitis and of the complete regression of lesions due to vasculitis without recurrence achieved with the scabies treatment alone, a diagnosis was made of scabietic vasculitis, probably as a result of cutaneous hypersensitivity reaction to humeral mediators.

FOXO3a and the MAPK p38 are activated by cetuximab to induce cell death and inhibit cell proliferation and their expression predicts cetuximab efficacy in colorectal cancer.

BACKGROUND: Cetuximab, a monoclonal antibody against EGFR used for the treatment of colorectal cancer (CRC), is ineffective in many patients. The aim of this study was to identify the signalling pathways activated by cetuximab in CRC cells and define new biomarker of response. METHODS: We used in vitro, in vivo models and clinical CRC samples to assess the role of p38 and FOXO3a in cetuximab mechanism of action. RESULTS: We show that cetuximab activates the MAPK p38. Specifically, p38 inhibition reduced cetuximab efficacy on cell growth and cell death. At the molecular level, cetuximab activates the transcription factor FOXO3a and promotes its nuclear translocation via p38-mediated phosphorylation, leading to the upregulation of its target genes p27 and BIM and the subsequent induction of apoptosis and inhibition of cell proliferation. Finally, we found that high FOXO3a and p38 expression levels are associated with better response rate and improved outcome in cetuximab-treated patients with CRC harbouring WT KRAS. CONCLUSIONS: We identify FOXO3a as a key mediator of cetuximab mechanism of action in CRC cells and define p38 as its activator in this context. Moreover, high FOXO3a and p38 expression could predict the response to cetuximab in patients with CRC harbouring WT KRAS.

[Differential diagnosis of basal cell carcinoma of the face: Dermatologist advice may avoid surgery]. / Diagnostics différentiels d'un carcinome basocellulaire de la face : l'avis du dermatologue pour éviter la chirurgie.

INTRODUCTION: Basal cell carcinoma (BCC) is the most common skin cancer in France. It is commonly diagnosed in front of a papule or nodule of the face. The surgeon should be able to question the diagnosis of BCC when nodular lesions are untypical, keeping in mind that some differential diagnoses require only medical treatment. OBSERVATIONS: The authors successively describe three non infectious entities mimicking BCC of the face, requiring purely medical treatment: facial granuloma described by Lever, cutaneous pseudolymphoma, sarcoidosis. DISCUSSION: In front of a non-typical skin nodule CBC, a dermatological expert advice may be quite helpful. The value of this collaboration is to guide or otherwise to suspend surgical excision.

[Pyoderma gangrenosum revealing colonic diverticulitis: Two cases]. / Pyoderma gangrenosum révélant une diverticulite colique: deux cas.

BACKGROUND: The association of pyoderma gangrenosum (PG) with colonic diverticulitis infection (DI) is relatively unknown. Herein, we describe two cases of PG with full recovery after colonic surgery. PATIENTS AND METHODS: Case 1: an 83-year-old man presented with lesions on his legs that had been present for several weeks, and a diagnosis of PG was confirmed histologically. Abdominopelvic computed tomography (CT) performed on account of biological inflammatory syndrome revealed DI complicated by abscesses. Following the failure of two different antibiotic regimens, sigmoidectomy was performed. Postoperatively, the skin lesions healed without local or systemic corticosteroids. Case 2: a 63-year-old woman presented PG resistant to local and systemic corticosteroids and dapsone for several months. A particularly severe flare was accompanied by abdominal pain and inflammatory syndrome. CT revealed perforated sigmoid DI. Sigmoidectomy was performed after failure of drug therapy. The patient's PG subsequently improved and had disappeared without recurrence at 24months. DISCUSSION: Both of these cases of PG revealed DI. The hypothesis is that DI constituted a source of colonic inflammation, sending out bacterial antigenic stimuli that resulted in PG through deposition of circulating immune complexes. Removal of this inflammatory source appears to have enabled healing of PG. CONCLUSION: DI must be added to the list of systemic diseases associated with PG. In the case of isolated PG, CT may be used to detect asymptomatic DI. Early diagnosis could prevent serious gastrointestinal complications.

[Plaque-like leiomyomas on a chemical burn: First case report]. / Léiomyomes en plaque sur brûlure chimique : première observation.

BACKGROUND: Cutaneous leiomyomas are uncommon benign smooth muscle neoplasms of skin of unknown pathogenesis. We report a sporadic case of multiple cutaneous leiomyomas at the site of a chemical burn. OBSERVATION: A 47-year-old male presented with multiple grouped red nodules on the right calf painful to cold and to touch. The lesions were located on the site of a chemical wound that had occurred 5 years earlier. Histopathological examination revealed a proliferation of smooth muscle fibres, leading to diagnosis of leiomyoma. DISCUSSION: To our knowledge, the literature contains no previous reports of sporadic multiple cutaneous leiomyomas occurring at a chemical burn site. While a chance association cannot be ruled out, there is also the possibility of a physiopathological mechanism similar to that of vascular tumours following exposure to 4-hydrazinobenzoic acid. This compound, a hydrazine derivative of the fungus Agaricus bisporus, can cause smooth-muscle tumours in the aorta and large vessels with morphological characteristics similar to those seen in vascular leiomyomas.

[Fatal alveolar haemorrhage following a "bang" of cannabis]. / Hémorragie alvéolaire fatale après bang de cannabis.

The new methods of cannabis consumption (home made water pipe or "bang") may be responsible for fatal respiratory complications. We present a case, with fatal outcome, of a man of 19 years with no previous history other than an addiction to cannabis using "bang". He was admitted to intensive care with acute dyspnoea. A CT scan showed bilateral, diffuse alveolar shadowing. He was anaemic with an Hb of 9.3g/l. Bronchoalveolar lavage revealed massive alveolar haemorrhage. Investigations for infection and immunological disorder were negative and toxicology was negative except for cannabis. Antibiotic treatment was given and favourable progress allowed early discharge. Death occurred 15 days later due to alveolar haemorrhage following a further "bang" of cannabis. Autopsy showed toxic alveolar haemorrhage. The probable mechanism is pulmonary damage due to acid anhydrides released by the incomplete combustion of cannabis in contact with plastic. These acids have a double effect on the lungs: a direct toxicity with severe inflammation of the mucosa leading to alveolar haemorrhage and subsequently the acid anhydrides may lead to the syndrome of intra-alveolar haemorrhage and anaemia described in occupational lung diseases by Herbert in Oxford in 1979. It manifests itself by haemoptysis and intravascular haemolysis. We draw attention to the extremely serious potential consequences of new methods of using cannabis, particularly the use of "bang" in homemade plastic materials.

[Retrospective study conducted in northern Finistère about the role of breast MRI in normal breast screening, experience in 51 patients]. / Etude rétrospective dans le Nord-Finistère sur la place de l'IRM mammaire devant un bilan sénologique normal, à propos de 51 cas.

OBJECTIVES: To study the role and indications of breast MRI in normal breast screening. PATIENTS AND METHODS: Retrospective study of 51 patients (mean age of 51 years) conducted in northern Finistère. Each patient had a normal (BI-RADS 1 or 2) breast screening (mammography and echography). Four indications for MRI were chosen: screening of high-risk patients, high-density breasts, radio-clinical discordance, and breasts prostheses. Breast MRI were reviewed according to BI-RADS classification. Abnormalities categorized in BI-RADS 4 or 5 were confirmed histologically. RESULTS: Thirteen patients underwent histological analysis. Nine invasive carcinomas were identified (six invasive lobular carcinomas (ILC), two mixed carcinomas, one invasive ductal carcinoma). For these patients, the reason for performing MRI was a radio-clinical discordance. DISCUSSION AND CONCLUSION: The study demonstrates the breast MRI value for radio-clinical discordance and the key role of MRI in diagnostic challenge of ILC. In literature review, MRI has a role even if breast screening is normal: radio-clinical discordance, screening of patients with high-risk, breasts prostheses in certain cases. Breast density comes as an additional criteria to perform this exam.

[Contribution of the CT scanner to the diagnosis of liposarcoma]. / Apport du scanner au diagnostic des liposarcomes.

Analysis of the CT aspect and anatomopathologic correlation of 11 liposarcomas of the abdomen and chest enabled definition of CT criteria for diagnosis. Anatomo-radiologic correlation could be established both for well-defined and poorly-defined tumors. However, due to the uneasy localization and high recurrence rate of poorly defined tumors, the data provided by CT did not improve the prognostic rates.

An unusual cause of sigmoid tumour: primary Hodgkin's disease. Case report.

Localized primary extranodal Hodgkin's disease is rare, especially in the digestive tract. A case is reported in which primary Hodgkin's disease presented as an ulcerated tumour of the sigmoid colon. The prognosis and management of such localized extranodal Hodgkin's lesions are discussed.

Primary pulmonary Hodgkin's disease and the dilemma of E stage.

Primary pulmonary Hodgkin's disease is rare. We report the case of a previously healthy 23-year-old woman who presented with isolated involvement of the right upper pulmonary lobe. Nodular sclerosing Hodgkin's disease was diagnosed after curative surgery. The clinical stage is felt to be IEBL+. The reasons for this staging, as opposed to a stage IV, are discussed. Adjuvant radiotherapy was given, delivering 39.6 grays in 22 courses of 1.8 grays. Three years after diagnosis, the patient is well and free of disease. A review of the literature indicates that the majority of primary pulmonary Hodgkin's disease present as a single mass amenable to curative surgery and radiation therapy. Chemotherapy can be reserved for the rare diffuse presentation.

[Occult gastric adenocarcinoma with pulmonary carcinomatous lymphangitis and microangiopathic hemolytic anemia in a young adult]. / Adénocarcinome gastrique occulte avec lymphangite carcinomateuse pulmonaire et anémie hémolytique microangiopathique chez un jeune adulte.

The case is reported of a 19-year-old patient with gastric carcinoma, in which clinical presentation (intermittent fever, myalgia, proximal muscle weakness and diffuse nodular-trabeculated infiltration of both lungs) was very unusual. The patient developed further complications (microangiopathic hemolytic anemia with disseminated intravascular coagulation) and died of subdural hematoma. Bone-marrow biopsy showed metastatic mucin-producing adenocarcinoma, but the gastric primary site of the tumor could only be demonstrated at autopsy.

[Cardiac myxoma. Ultrastructural and immunohistochemical study of two cases]. / Myxome cardiaque. Etude ultrastructurale et immunohistochimique de deux cas.

Two cases of cardiac myxoma studied by electron microscopy and by immunohistochemical methods are reported. In one case, the initial clinical manifestation was systemic embolization, and histological sections from the arterial deobstruction material set the diagnosis of an embolizing cardiac myxoma. In the second case, the investigations of a post-capillary pulmonary hypertension with echocardiography disclosed a left intraauricular tumor. Ultrastructural studies demonstrated mesenchymal tumor cells of various degrees of differentiation characterized by numerous cytoplasmic microfilaments and intermediate-sized filaments. The most differentiated cells were surrounded by a continuous basement membrane; there were intracellular junctions and microvilli. Furthermore these cells contained numerous micropinocytosis vesicles, several Weibel-Palade bodies and an abundant rough endoplasmic reticulum. Analysis of their cytoskeleton, using indirect immunofluorescnece techniques, showed that these cells were laden with actin and myosin microfilaments; the intermediate filaments were composed of vimentine. Staining with anti-desmin and anti-prekeratin sera remained negative. These results contribute to confirm that cardiac myxomas represent tumors originating from the primitive multipotential mesenchymal cells. An obvious tendency to differentiate into endothelial cells is noted in the two cases studied.

Primary aldosteronism with bilateral adrenal adenomas.

An unusual case of primary aldosteronism with bilateral single adenomas is reported. The two tumors were revealed by computerized axial tomography and subsequently confirmed by surgical exploration. Spironolactone therapy prior to the operation induced the formation of spironolactone bodies in only one of the two adenomas. As it has been postulated that these cytoplasmic inclusions may reflect the activity of the adenomatous cells, the presence of the bodies in a single adenoma would indicate a unilateral source of the hyperaldosteronism. Thus, the existence of spironolactone bodies could corroborate the data of functional localizing tests more closely than the morphological findings of computerized tomography.

[Lymph node lesions simulating a malignant lymphoma]. / Les lymphadénopathies simulant un lymphome malin.

Examples are reported of lymph node lesions simulating histologically and/or clinically malignant lymphomas. Two main categories of alterations have been distinguished: A. hyperplastic lymph node alterations associated with systemic disease and/or viral or drug-induced lymphadenitis; B. anatomo-clinical entities such as giant lymph node hyperplasia, massive lymphadenopathy with sinus histiocytosis, and angio-immunoblastic lymphadenopathy. It is suggested that in some situations such as angio-immunoblastic lymphadenopathy the borderline between reactive and enoplastic alterations is not clear cut. To evaluate such changes, close collaboration between the clinician, the hematologist and the patholigist is necessary.