Jean-Marc Joseph

• MD, PD & MER
• Medical Doctor at Lausanne University Hospital

Background: Acute appendicitis is the most frequent surgical emergency in the paediatric population. Complicated appendicitis accounts for 30% of cases and is inextricably linked to postoperative infectious complications. A study at our institution showed that amoxicillin-clavulanate resistant Escherichia coli in complicated appendicitis was signi...

Reconstruction of large chest wall defects is challenging. Here we discuss the process of decision-making in planning chest wall reconstruction, considering the requirements of tumor removal, stabilization of the chest wall, and soft tissue coverage, illustrated by a case of a hemi-chest wall defect in a child. Ewing sarcoma measuring 10 × 9 × 13 c...

The embryonic transcription factors TWIST1/2 are frequently overexpressed in cancer, acting as multifunctional oncogenes. Here we investigate their role in neuroblastoma (NB), a heterogeneous childhood malignancy ranging from spontaneous regression to dismal outcomes despite multimodal therapy. We first reveal the association of TWIST1 expression w...

Human populations of Black African ancestry have a relatively high risk of aggressive cancer types, including keratinocyte-derived squamous cell carcinomas (SCCs). We show that primary keratinocytes (HKCs) from Black African (Black) versus White Caucasian (White) individuals have on average higher oncogenic and self-renewal potential, which are inv...

The embryonic transcription factors TWIST1/2 are frequently overexpressed in cancer, acting as multifunctional oncogenes. Here we investigate their role in neuroblastoma (NB), a heterogeneous childhood malignancy ranging from spontaneous regression to dismal outcomes despite multimodal therapy. We first reveal the association of TWIST1 expression w...

PURPOSE To evaluate the impact of surgeon-assessed extent of primary tumor resection on local progression and survival in patients in the International Society of Pediatric Oncology Europe Neuroblastoma Group High-Risk Neuroblastoma 1 trial. PATIENTS AND METHODS Patients recruited between 2002 and 2015 with stage 4 disease > 1 year or stage 4/4S w...

Children with sickle cell disease (SCD) require specific perioperative care, and clinical practice in this area remains poorly defined. We aimed to conduct a systematic, PRISMA‐based review of the literature, available clinical guidelines and practice recommendations. We also aimed to extract any valuable information for the “best of available‐evid...

Background Children with sickle cell disease (SCD) frequently require in‐ or outpatient surgical procedures for various indications, including complications secondary to SCD itself. To prevent adverse events associated with an increased morbidity/mortality, these vulnerable patients need specific perioperative care. However, clinical practice in th...

Background: Choice of antibiotics for complicated appendicitis should address local antibiotic resistance patterns. As our local data showed a less than 15% resistance of Escherichia coli to co-amoxicillin (amoxicillin + clavulanic acid), we opted for this antibiotic in 2013. Subsequently, the increasing prevalence of Pseudomonas aeruginosa challe...

Background The successful targeting of neuroblastoma (NB) by associating tumor-initiating cells (TICs) is a major challenge in the development of new therapeutic strategies. The subfamily of aldehyde dehydrogenases 1 (ALDH1) isoenzymes, which comprises ALDH1A1, ALDH1A2, and ALDH1A3, is involved in the synthesis of retinoic acid, and has been identi...

CSL is a key transcriptional repressor and mediator of Notch signaling. Despite wide interest in CSL, mechanisms responsible for its own regulation are little studied. CSL down-modulation in human dermal fibroblasts (HDFs) leads to conversion into cancer associated fibroblasts (CAF), promoting keratinocyte tumors. We show here that CSL transcript l...

Objectives: This study aimed to identify, through systematic literature review, the most reliable clinical, biological, and radiological signs of ovarian torsion in the pediatric population and to compare their diagnostic value. Methods: This is a systematic review of the literature, searching MEDLINE, EMBASE, and Cochrane Databases for articles...

To evaluate the levels of satisfaction and opinions on the usefulness of the informed consent form currently in use in our Paediatric Surgery Department. Qualitative study carried out via interviews of senior paediatric surgeons, based on a questionnaire built up from reference criteria in the literature and public health law. Physicians with betw...

Neuroblastoma (NB) is one of the most deadly solid tumors of the young child, for which new efficient and targeted therapies are strongly needed. The CXCR4/CXCR7/CXCL12 chemokine axis has been involved in the progression and organ-specific dissemination of various cancers. In NB, CXCR4 expression was shown to be associated to highly aggressive undi...

s: AACR Special Conference: Pediatric Cancer at the Crossroads: Translating Discovery into Improved Outcomes; November 3-6, 2013; San Diego, CA Neuroblastoma (NB), a neural crest-derived embryonal tumor, is a heterogeneous childhood malignancy that often presents as an incurable disease. The anaplastic lymphoma receptor tyrosine kinase gene (ALK)...

The Wnt pathway is abnormally activated in the majority of colorectal cancers, and significant knowledge has been gained in understanding its role in tumor initiation. However, the mechanisms of metastatic outgrowth in colorectal cancer remain a major challenge. We report that autophagy-dependent metabolic adaptation and survival of metastatic colo...

Background The aim of our study was to assess the postoperative course of bilateral anterior sternothoracotomy (BAT) in children with sarcoma metastases, in a curative care perspective. Methods We reviewed the records of seven patients younger than 18 years old, who underwent surgical procedures for sarcoma metastasis to the lung between 2000 and...

The anaplastic lymphoma kinase (ALK) gene is overexpressed, mutated or amplified in most neuroblastoma (NB), a pediatric neural crest-derived embryonal tumor. The two most frequent mutations, ALK-F1174L and ALK-R1275Q, contribute to NB tumorigenesis in mouse models, and cooperate with MYCN in the oncogenic process. However, the precise role of acti...

Quality of care and its measurement represent a considerable challenge for pediatric smaller-scale comprehensive cancer centers (pSSCC) providing surgical oncology services. It remains unclear whether center size and/or yearly case-flow numbers influence the quality of care, and therefore impact outcomes for this population of patients. We performe...

Livre de référence consensuel, orienté vers une Médecine basée sur l’évidence et une démarche clinique raisonnée. Il s’appuie sur les recommandations soutenues par les scientifiques du domaine concerné. Chaque chapitre s’articule sur le même modèle: texte court, algorithme et références bibliographiques essentielles Une première partie concerne les...

Osteosarcoma metastasis causing intussusception is a very rare entity, with a pejorative prognosis. Based on a case, we performed a literature review in order to better assess this situation. We conclude that, in patients with a history of osteosarcoma lung metastasis, echographic and/or computed tomography scan evidence of a small bowel obstructio...

Neuroblastoma (NB) is a typical childhood and heterogeneous neoplasm for which efficient targeted therapies for high-risk tumors are not yet identified. The chemokine CXCL12, and its receptors CXCR4 and CXCR7 have been involved in tumor progression and dissemination. While CXCR4 expression is associated to undifferentiated tumors and poor prognosis...

CXCR7 mRNA expression levels upon differentiation of NB cells in vitro. (A) Semi-quantitative real-time PCR analyses of CXCR7 mRNA expression levels upon treatment of SH-SY5Y cells with 10 µM RA or BrdU for 3 days. (B) The SK-N-Be(2c) and the IGR-NB8 cell lines were treated with 10 µM RA. Untreated cells (unt.) or cells exposed to DMSO were used as...

Characteristics of NB cells after RA or BrdU treatment in vitro. (A) SK-N-Be(2c) cells were exposed to either 10 µM all-trans Retinoic Acid (RA) or 5-bromo-2-deoxyuridine (BrdU) for 3 and 30 days. Images illustrate immunofluoresence staining of β3-tubulin (red) and DAPI (blue). RA-treated NB cells elaborated enhanced neuritic processes and prolifer...

Expression of CXCR7 and CXCL12 in NB clinical groups. CXCR7 and CXCL12 expression, as associated to neural, endothelial and stromal cell compartments, were measured in INSS neuroblastoma clinical groups. (DOC)

Akt pathway activation in NB cell lines. Immunobloting of phospho-Akt (pAkt) and total Akt (Akt) in NB transduced cells, stimulated with (A) 100 ng/ml CXCL12, or (B) 100 ng/ml CXCL11 at indicated time points. NB transduced cells were also treated with 10 ng/ml IGF-1 for 1 h, as positive control [69]. (TIF)

Neuroblastoma (NB) is a neural crest-derived childhood tumor characterized by a remarkable phenotypic diversity, ranging from spontaneous regression to fatal metastatic disease. Although the cancer stem cell (CSC) model provides a trail to characterize the cells responsible for tumor onset, the NB tumor-initiating cell (TIC) has not been identified...

Purpose Totally implanted vascular (TIVA) ports are used in children for repeated blood samples or intravenous treatments. We have recently published a prospective evaluation of surgical incidents and early complications associated with these devices. This work is the final part of the same study, assessing late complications over a follow-up of 2...

Cyclooxyganase-2 (COX-2), a rate-limiting enzyme in the prostaglandin synthesis pathway, is overexpressed in many cancers and contributes to cancer progression through tumor cell-autonomous and paracrine effects. Regular use of non-steroidal anti-inflammatory drugs or selective COX-2 inhibitors (COXIBs) reduces the risk of cancer development and pr...

Cancer stem cells (CSCs) display plasticity and self-renewal properties reminiscent of normal tissue stem cells, but the events responsible for their emergence remain obscure. We recently identified CSCs in Ewing sarcoma family tumors (ESFTs) and showed that they retain mesenchymal stem cell (MSC) plasticity. In the present study, we addressed the...

The development of chemoresistance represents a major obstacle in the successful treatment of cancers such as neuroblastoma (NB), a particularly aggressive childhood solid tumour. The mechanisms underlying the chemoresistant phenotype in NB were addressed by gene expression profiling of two doxorubicin (DoxR)-resistant vs sensitive parental cell li...

Primary rib involvement accounts for 16% of paediatric Ewing sarcoma (ES). Neo-adjuvant chemotherapy and surgical tumor resection may leave large thoracic wall defects requiring complex reconstruction in a growing individual. We report our experience in three children aged 3, 10, and 12 years, in whom single-stage resection and reconstruction were...

Cancer stem cells that display tumor-initiating properties have recently been identified in several distinct types of malignancies, holding promise for more effective therapeutic strategies. However, evidence of such cells in sarcomas, which include some of the most aggressive and therapy-resistant tumors, has not been shown to date. Here, we ident...

Totally implanted vascular access devices are frequently used in children for repeated blood samples or intravenous treatments. This prospective study aims at identifying the risk factors associated with infections, obstructions and surgical complications of these devices in pediatric patients. From January 2006 to January 2008, all children older...

We describe a new procedure of digestive reconstruction after pylorus-preserving pancreaticoduodenectomy in a 13-year-old girl presenting with a large solid and papillary epithelial neoplasm of the pancreatic head. A midgut transposition (like in a cure of midgut malrotation) was easily performed after tumor removal with minimal additional dissecti...

Central venous occlusion in children is a challenging problem that can occur after a central venous catheter insertion. Long-term catheter-related complications include sepsis and venous thrombosis with consequent loss of central access. We describe 2 cases of children younger than 1 year who were dependent on a central venous catheter for total pa...

Ewing's sarcoma family tumors (ESFT) express the EWS-FLI-1 fusion gene generated by the chromosomal translocation t(11;22)(q24;q12). Expression of the EWS-FLI-1 fusion protein in a permissive cellular environment is believed to play a key role in ESFT pathogenesis. However, EWS-FLI-1 induces growth arrest or apoptosis in differentiated primary cell...

Histone deacetylase inhibitors (HDACi) are a new class of promising anti-tumour agent inhibiting cell proliferation and survival in tumour cells with very low toxicity toward normal cells. Neuroblastoma (NB) is the second most common solid tumour in children still associated with poor outcome in higher stages and, thus NB strongly requires novel tr...

A 16-month-old boy presented with a story of stridor, solid dysphagia and a history of spectacular protrusion underneath his tongue which was mistaken by the parents for a snake's tongue! The radiological examinations showed a filling defect of the upper and middle third esophagus which compressed the cervical trachea. This was found to be an intra...

Neuroblastoma (NB) is a heterogeneous, and particularly malignant childhood neoplasm in its higher stages, with a propensity to form metastasis in selected organs, in particular liver and bone marrow, and for which there is still no efficient treatment available beyond surgery. Recent evidence indicates that the CXCR4/CXCL12 chemokine/receptor axis...

In vivo neuroblastoma (NB) xenograft model, resistant to the DNA-topoisomerase I inhibitor irinotecan (CPT-11), has been established to study resistance mechanisms acquired in a therapeutic setting. Common mechanisms of resistance were not involved in this resistance. Thus, we compared the gene expression profiles of sensitive, resistant, and rever...

Neuroblastoma is a heterogeneous neural crest-derived embryonic childhood neoplasm that is the second most common solid tumor found in children. Despite recent advances in combined therapy, the overall survival of patients with high-stage disease has not improved in the last decades. Treatment failure is in part attributed to multidrug resistance....

Neuroblastoma represents the most common and deadly solid tumour of childhood, which disparate biological and clinical behaviour can be explained by differential regulation of apoptosis. To understand mechanisms underlying death resistance in neuroblastoma cells, we developed small hairpin of RNA produced by lentiviral vectors as tools to selective...

Neuroblastoma (NB) is the second most common solid childhood tumour, an aggressive disease for which new therapeutic strategies are strongly needed. Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in most tumour cells, but not in normal tissues and therefore represents a valuable candidate in apoptosis...

Human neuroblastoma (NB) is the second most frequent solid tumor of childhood and represents a highly heterogeneous disease at clinical and biologic levels. Little progress has been made to improve the poor prognosis of patients with high-stage NB. Tumor progression and metastatic dissemination still represent major obstacles to the successful trea...

Neuroblastoma (NB) is a childhood neoplasm which heterogeneous behavior can be explained by differential regulation of apoptosis. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively induces rapid apoptosis in most tumor cells and thus represents a promising anticancer agent. We have reported silencing of caspase-8 expression...

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in most tumor cells, a process sometimes potentiated by chemotherapeutic drugs or cycloheximide (CHX). Childhood neuroblastoma (NB) is a clinically and biologically heterogeneous neoplasm whose behavior can be explained by differential regulation of apopto...

Human neuroblastoma (NB) is a highly heterogeneous childhood cancer secreting a high level of vascular endothelial growth factor (VEGF). Its vascularization has been clearly correlated with metastatic progression and poor outcome. Thus, molecules that target the vascular endothelium are regarded as new therapeutics of clinical interest. Angiostatin...

Retroviral-mediated gene therapy has been proposed as a primary or adjuvant treatment for advanced cancer, because retroviruses selectively infect dividing cells. Efficacy of retroviral-mediated gene transfer, however, is limited in vivo. Although packaging cell lines can produce viral vectors continuously, such allo- or xenogeneic cells are normal...

Bilateral fetal rhabdomyomatous nephroblastoma is a rare variant of Wilms' Tumor. The authors report the evolution over 48 months of a 10-month-old baby with bilateral nephroblastoma for which a left nephrectomy was initially performed. A right kidney tumor was enucleated preserving the kidney. The transformation of the primary tumor into a complet...

Isolated phlebitis of the gastrointestinal tract is rare and potentially life threatening. We report on a patient who developed peritonitis, requiring emergency laparotomy, total colectomy, and ileostomy because of colon necrosis. The specimen displayed multiple ulcerations and erosions. Histology showed a predominantly lymphocytic infiltrate of sm...

Objective: To investigate, during endotoxic shock, the effect of a treatment of norepinephrine (NE) administration on the distribution of blood flow and adenosine triphosphate (ATP) content in the intestinal wall. Design: Randomized controlled trial. Setting: Animal laboratory. Subjects: Domestic pigs. Intervention: A total of 18 pigs were anesthet...

Huntington's disease (HD) is an inherited disorder characterized by cognitive impairments, motor deficits, and progressive dementia. These symptoms result from progressive neurodegenerative changes mainly affecting the neostriatum. This pathology is fatal in 10 to 20 years and there is currently no treatment for HD. Early in the course of the disea...

Neurotrophic factors may be of therapeutic importance for the treatment of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD). The transplantation of polymer-encapsulated cells genetically engineered to continuously release neurotrophic factors at a relatively low dose is an extremely useful tool. Ce...

Neurotrophic factors hold promise for the treatment of neurodegenerative diseases. Intrathecal transplantation of polymer encapsulated cell lines genetically engineered to release neurotrophic factors provides a means to deliver them continuously behind the blood-brain barrier. Long-term delivery, however, may benefit from the use of conditionally...

Chromaffin cells from the adrenal gland secrete a mixture of compounds that have a strong analgesic effect, especially when administered intrathecally. Many studies in animal models have shown that discordant xenogeneic cell isolates, including chromaffin cells, can survive and have biologic effects when transplanted within a semipermeable membrane...

Neuronal growth factors hold promise for providing therapeutic benefits in various neurological disorders. As a means of ensuring adequate central nervous system delivery of growth factors and minimizing significant adverse side effects associated with systemic delivery methods, we have developed an ex vivo gene therapy approach for protein deliver...

The gene therapy approach presented in this protocol employs a polymer encapsulated, xenogenic, transfected cell line to release human ciliary neurotrophic factor (hCNTF) for the treatment of Amyotrophic Lateral Sclerosis (ALS). A tethered device, containing around 10(6) genetically modified cells surrounded by a semipermeable membrane, is implante...

BACKGROUND: Chromaffin cells from the adrenal gland secrete a mixture of compounds that have a strong analgesic effect, especially when administered intrathecally. Many studies in animal models have shown that discordant xenogeneic cell isolates, including chromaffin cells, can survive and have biologic effects when transplanted within a semipermea...

Keywords: Adrenal Medulla/cytology ; Animals ; Cattle ; Cell Transplantation/methods ; Humans ; Immune Tolerance ; Prostheses and Implants ; Transplantation Immunology ; Transplantation ; Heterologous Note: Department of Neurosurgery Centre Hospitalier Universitaire Vaudois University of Lausanne Medical School, Switzerland. Reference LEN-ARTICLE-1...

We report two recent observations of an angiographic artefact called "standing waves". It results in the same characteristic beaded pictures than fibromuscular dysplasia. It is induced by the angiography catheter and is related to the speed of injection. The possible occurrence of this artefact should be borne in mind whenever the films show dyspla...

Chromaffin cells have been shown to release a combination of pain-reducing neuroactive compounds including catecholamines and opioid peptides. The allogeneic transplantation of chromaffin cells in the subarachnoid space has been shown to alleviate pain in various rodent models and possibly in terminal cancer patients. Because of the shortage of hum...

A consecutive series of 50 patients who submitted to 53 hepatic resections with use of continuous normothermic liver ischemia is reported. Portal triad clamping has been used in 28 cases, with associated inferior vena caval clamping above and below the liver (hepatic vascular exclusion) in 25 patients. The size of the tumor required major hepatic r...

In 1987, two media campaigns were organized in Switzerland to promote donor cards. The purpose of this study was to test their impact on the medical community. Questionnaires were sent to qualified practitioners, doctors in training and intensive care nurses. It is concluded that the campaigns for organ donation must be repeated and that their qual...