Dramatic malignant progression of a pigmented villonodular synovitis of the knee after 27 years of multimodality treatment

Introduction: Pigmented villonodular synovitis (PVNS) is a rare benign tumour of the synovium, most commonly arising around the knee. Resection remains the treatment of choice. The diffuse variant of the disease is prone to local recurrence (30-50%). However distant dissemination is extremely rare. We report the case of a patient with massive loco-regional and late distant spread to the lungs of PVNS originating in the knee. Case report: A 69 yo women presented to our service 27 years ago with PVNS in her knee. Despite multible surgical resections, synoviorthesis and external beam radiotherapy, no local control was achieved. The disease spread in all thigh compartments. Due to the resistance to all convetional treatment modalities, isolated limb perfusion with TNFα and Melphalan was performed, without any effect on local control. After the disease was diagnosed in iliac lymph nodes, the patient was subjected to a systemic chemotherapy protocol with imitamib, which had to be abandoned, due to intolerance. Due to a giant lymphoedema of the entire limb, making up for a considerable part of the patient's body weight and in view of significant skin invasion, a hip disarticulation was performed. Finally, rapidly growing lung metastases appeared on CT scan, confirmed by core-needle biopsy. Palliative chemotherapy was initiated. Interestingly, histological analysis of the disease throughout the years remained consistent with classic benign PVNS. No sarcomatous dedifferentiation was observed, not even in the pulmonary lesions. Conclusion: PVNS is a benign tumour, with a high risk of local recurrence. Malignant behaviour, with loco-regional and distant metastases remains extremely rare. A histologically benign appearance does not exclude a clinically malignant behaviour with systemic spread.

Seismic reflectivity of the sediment-covered seafloor: Effects of velocity gradients and fine-scale layering

Knowledge of the reflectivity of the sediment-covered seabed is of significant importance to marine seismic data acquisition and interpretation as it governs the generation of reverberations in the water layer. In this context pertinent, but largely unresolved, questions concern the importance of the typically very prominent vertical seismic velocity gradients as well as the potential presence and magnitude of anisotropy in soft surficial seabed sediments. To address these issues, we explore the seismic properties of granulometric end-member-type clastic sedimentary seabed models consisting of sand, silt, and clay as well as scale-invariant stochastic layer sequences of these components characterized by realistic vertical gradients of the P- and S-wave velocities. Using effective media theory, we then assess the nature and magnitude of seismic anisotropy associated with these models. Our results indicate that anisotropy is rather benign for P-waves, and that the S-wave velocities in the axial directions differ only slightly. Because of the very high P- to S-wave velocity ratios in the vicinity of the seabed our models nevertheless suggest that S-wave triplications may occur at very small incidence angles. To numerically evaluate the P-wave reflection coefficient of our seabed models, we apply a frequency-slowness technique to the corresponding synthetic seismic wavefields. Comparison with analytical plane-wave reflection coefficients calculated for corresponding isotropic elastic half-space models shows that the differences tend to be most pronounced in the vicinity of the elastic equivalent of the critical angle as well as in the post-critical range. We also find that the presence of intrinsic anisotropy in the clay component of our layered models tends to dramatically reduce the overall magnitude of the P-wave reflection coefficient as well as its variation with incidence angle.

Propionibacterium avidum sacroiliitis and osteomyelitis.

The anaerobic Gram-positive bacterium Propionibacterium avidum is a common inhabitant of the skin with low pathogenicity. We report a case of P. avidum sacroilitis, psoas abscess and osteomyelitis in a 67-year-old male who had recently undergone surgical repair of an inguinal hernia. The organism was recovered from blood cultures, a bone biopsy specimen and specimens from the abscess. The spectrum of bone and joint infections caused by Propionibacterium is discussed. Infection by Propionibacterium spp. should be considered in patients with bone and joint infections.

Visceral leishmaniasis and hemophagocytic syndrome

A 11 months old female infant from Portugal, free of family history, consults for apathy, weight loss, tachycardia, tachypnea, petechiae, pallor without icterus and hepatoslenomegaly. Seven months earlier, while being in Portugal, she presented a persistent bluish pimple on her buttock. Laboratory results showed anemia (35 g/l), leucopenia (3.3 G/l), thrombocytopenia (13 G/l), impaired coagulation (INR 1.4, PTT 41 sec.), hyponatremia (124 mmol/l), elevated CRP (139 mg/l), high ferritin (34.775 μg/l) and high triglycerides (5.22 mmol/l). After correction of vital parameters, a bone marrow aspiration and biopsy (BMB) revealed both the etiological diagnosis, namely a visceral leishmaniasis (VL) as well as one of its potential complications, the hemophagocytic syndrome (HS). Transfusions of whole blood, platelets and fresh frozen plasma were immediately started. Dexamethasone (10 mg/m2) and amphotericin B (3 mg/kg/day) have also been administrated. Visceral leishmaniasis is caused by a protozoan (Leishmania donovani) transmitted by the female sandfly. It is endemic in the Mediterranean basin (including France, Italy, Spain and Portugal), South America, sub-Saharan Africa as well as in India and Bangladesh. The parasite infects macrophages and, after several weeks of incubation, the disease occurs by affection of bloodlines (anemia, leucopenia, thrombocytopenia), hepatosplenomegaly, cachexia, gastrointestinal damage. The complications of the disease may lead to death. Liposomal amphotericin B is the currently recommended treatment. HS is caused by the proliferation and activation of macrophages in the marrow in response to a cytokine storm. It may be of primary cause. When it is secondary, it may be related to infections such as leishmaniasis. Patients present with fever and laboratory diagnostic criteria include cytopenia, hypertriglyceridemia, high ferritin and hemophagocytosis in the BMB. The treatment consists among other in the administration of high doses corticosteroids and, in secondary cases, in the treatment of the underlying cause. In conclusion, the clinical and biological features of VL may mimic haematological disorders as leukemia, but an enlargement of the liver and especially of the spleen should remind in this parasitic infection and its potential fatal complication, the HS.

Axillary Sentinel Lymph Node Biopsy for Breast Cancer and Melanoma Patients after Previous Axillary Surgery: A Systematic Review

Objective: Sentinel lymph node biopsy (SLNB) is a validated staging technique for breast carcinoma. Some women are exposed to have a second SLNB due to breast cancer recurrence or a second neoplasia (breast or other). Due to modi- fied anatomy, it has been claimed that previous axillary surgery represents a contra-indication to SLNB. Our objective was to analyse the literature to assess if a second SLNB is to be recommended or not. Methods: For the present study, we performed a review of all published data during the last 10 years on patients with previous axilla surgery and second SLNB. Results: Our analysis shows that second SLNB is feasible in 70%. Extra-axillary SNs rate (31%) was higher after radical lymph node dissection (ALND) (60% - 84%) than after SLNB alone (14% - 65%). Follow-up and com- plementary ALND following negative and positive second SLNB shows that it is a reliable procedure. Conclusion: The review of literature confirms that SLNB is feasible after previous axillary dissection. Triple technique for SN mapping is the best examination to highlight modified lymphatic anatomy and shows definitively where SLNB must be per- formed. Surgery may be more demanding as patients may have more frequently extra-axillary SN only, like internal mammary nodes. ALND can be avoided when second SLNB harvests negative SNs. These conclusions should however be taken with caution because of the heterogeneity of publications regarding SLNB and surgical technique.

The role of fungi in the precipitation of calcite : relationships between fungal filaments, nanofibres, and needle fibre calcite

RésuméLes champignons sont impliqués dans les cycles biogéochimiques de différentes manières. En particulier, ils sont reconnus en tant qu'acteurs clés dans la dégradation de la matière organique, comme fournisseurs d'éléments nutritifs via l'altération des minéraux mais aussi comme grands producteurs d'acide oxalique et de complexes oxalo-métalliques. Toutefois, peu de choses sont connues quant à leur contribution à la genèse d'autres types de minéraux, tel que le carbonate de calcium (CaCO3). Le CaCO3 est un minéral ubiquiste dans de nombreux écosystèmes et il joue un rôle essentiel dans les cycles biogéochimiques du carbone (C) et du calcium (Ca). Le CaCO3 peut être d'origine physico-chimique ou biogénique et de nombreux organismes sont connus pour contrôler ou induire sa biominéralisation. Les champignons ont souvent été soupçonnés d'être impliqué dans ce processus, cependant il existe très peu d'informations pour étayer cette hypothèse.Cette thèse a eu pour but l'étude de cet aspect négligé de l'impact des champignons dans les cycles biogéochimiques, par l'exploration de leur implication potentielle dans la formation d'un type particulier de CaCO3 secondaires observés dans les sols et dans les grottes des environnements calcaires. Dans les grottes, ces dépôts sont appelés moonmilk, alors que dans les sols on les appelle calcite en aiguilles. Cependant ces deux descriptions correspondent en fait au même assemblage microscopique de deux habitus particulier de la calcite: la calcite en aiguilles (au sens strict du terme cette fois-ci) et les nanofibres. Ces deux éléments sont des habitus aciculaires de la calcite, mais présentent des dimensions différentes. Leur origine, physico-chimique ou biologique, est l'objet de débats intenses depuis plusieurs années déjà.L'observation d'échantillons environnementaux avec des techniques de microscopie (microscopie électronique et micromorphologie), ainsi que de la microanalyse EDX, ont démontré plusieurs relations intéressantes entre la calcite en aiguilles, les nanofibres et des éléments organiques. Premièrement, il est montré que les nanofibres peuvent être organiques ou minérales. Deuxièmement, la calcite en aiguilles et les nanofibres présentent de fortes analogies avec des structures hyphales, ce qui permet de confirmer l'hypothèse de leur origine fongique. En outre, des expériences en laboratoire ont confirmé l'origine fongique des nanofibres, par des digestions enzymatiques d'hyphes fongiques. En effet, des structures à base de nanofibres, similaires à celles observées dans des échantillons naturels, ont pu être produites par cette approche. Finalement, des enrichissements en calcium ont été mesurés dans les parois des hyphes et dans des inclusions intrahyphales provenant d'échantillons naturels de rhizomorphes. Ces résultats suggèrent une implication de la séquestration de calcium dans la formation de la calcite en aiguilles et/ou des nanofibres.Plusieurs aspects restent à élucider, en particulier la compréhension des processus physiologiques impliqués dans la nucléation de calcite dans les hyphes fongiques. Cependant, les résultats obtenus dans cette thèse ont permis de confirmer l'implication des champignons dans la formation de la calcite en aiguilles et des nanofibres. Ces découvertes sont d'une grande importance dans les cycles biogéochimiques puisqu'ils apportent de nouveaux éléments dans le cycle couplé C-Ca. Classiquement, les champignons sont considérés comme étant impliqués principalement dans la minéralisation de la matière organique et dans l'altération minérale. Cette étude démontre que les champignons doivent aussi être pris en compte en tant qu'agents majeurs de la genèse de minéraux, en particulier de CaCO3. Ceci représente une toute nouvelle perspective en géomycologie quant à la participation des champignons au cycle biologique du C. En effet, la présence de ces précipitations de CaCO3 secondaires représente un court-circuit dans le cycle biologique du C puisque du C inorganique du sol se retrouve piégé dans de la calcite plutôt que d'être retourné dans l'atmosphère.AbstractFungi are known to be involved in biogeochemical cycles in numerous ways. In particular, they are recognized as key players in organic matter recycling, as nutrient suppliers via mineral weathering, as well as large producers of oxalic acid and metal-oxalate. However, little is known about their contribution to the genesis of other types of minerals such as calcium carbonate (CaCO3). Yet, CaC03 are ubiquitous minerals in many ecosystems and play an essential role in the biogeochemical cycles of both carbon (C) and calcium (Ca). CaC03 may be physicochemical or biogenic in origin and numerous organisms have been recognized to control or induce calcite biomineralization. While fungi have often been suspected to be involved in this process, only scarce information support this hypothesis.This Ph.D. thesis aims at investigating this disregarded aspect of fungal impact on biogeochemical cycles by exploring their possible implication in the formation of a particular type of secondary CaC03 deposit ubiquitously observed in soils and caves from calcareous environments. In caves, these deposits are known as moonmilk, whereas in soils, they are known as Needle Fibre Calcite (NFC - sensu lato). However, they both correspond to the same microscopic assemblage of two distinct and unusual habits of calcite: NFC {sensu stricto) and nanofibres. Both features are acicular habits of calcite displaying different dimensions. Whether these habits are physicochemical or biogenic in origin has been under discussion for a long time.Observations of natural samples using microscopic techniques (electron microscopy and micromorphology) and EDX microanalyses have demonstrated several interesting relationships between NFC, nanofibres, and organic features. First, it has shown that nanofibres can be either organic or minera! in nature. Second, both nanofibres and NFC display strong structural analogies with fungal hyphal features, supporting their fungal origin. Furthermore, laboratory experiments have confirmed the fungal origin of nanofibres through an enzymatic digestion of fungal hyphae. Indeed, structures made of nanofibres with similar features as those observed in natural samples have been produced. Finally, calcium enrichments have been measured in both cell walls and intrahyphal inclusions of hyphae from rhizomorphs sampled in the natural environment. These results point out an involvement of calcium sequestration in nanofibres and/or NFC genesis.Several aspects need further investigation, in particular the understanding of the physiological processes involved in hyphal calcite nucleation. However, the results obtained during this study have allowed the confirmation of the implication of fungi in the formation of both NFC and nanofibres. These findings are of great importance regarding global biogeochemical cycles as they bring new insights into the coupled C and Ca cycles. Conventionally, fungi are considered to be involved in organic matter mineralization and mineral weathering. In this study, we demonstrate that they must also be considered as major agents in mineral genesis, in particular CaC03. This is a completely new perspective in geomycology regarding the role of fungi in the short-term (or biological) C cycle. Indeed, the presence of these secondary CaC03 precipitations represents a bypass in the short- term carbon cycle, as soil inorganic C is not readily returned to the atmosphere.

Neoadjuvant therapy with denosumab in a giant cell tumour. A case report

Introduction: Giant cell tumour (GCT) is a benign but locally aggressive primary osteolytic bone tumour, prone to local recurrence after surgery. Denosumab is a human antibody against RANKL, an over-expressed ligand present on normal multinucleated cells, responsible for bone destruction in GCT. We report the case of a patient with an advanced GCT of the distal radius. The lesion was treated with adjuvant denosumab , followed by curettage. Clinical case: A 28 years old patient presented with a classical honeycomb osteolytic lesion in the left distal radius. Core-needle biopsy confirmed the diagnosis of GCT. Due to the proximity to the radio-carpal joint and advanced scalloping of the metaphyseal cortical bone, joint-salvage surgery was not possible. We initiated a neo-adjuvant treatment with denosumab (XGEVA), 120mg/ week for 1 month, followed by monthly injections for 6 months. During this time, a substantial bone recorticalization, without progression of the size of the tumour was noted. No local or systemic side effects were observed. We performed intra-lesional (curettage) excision and bone grafting after 6 months. Histological analysis revealed islets (10%) of viable tumour cells within fibrous tissue. Post-op evolution was eventless. Discussion: While surgery remains the treatment of choice for GCT, joint-salvage may not always be possible in case of extensive epiphyseal involvement. The presence of osteoclast-like giant cells seems to make those lesions prone to the specific anti-RANKL treatment with denosumab. Denosumab appears to slow down tumour growth and promote recorticalization of eroded bone. It might allow less aggressive surgery in selected cases.

Sentinel lymph node biopsy in nonmelanoma skin cancer patients.

The management of lymph nodes in nonmelanoma skin cancer patients is currently still debated. Merkel cell carcinoma (MCC), squamous cell carcinoma (SCC), pigmented epithelioid melanocytoma (PEM), and other rare skin neoplasms have a well-known risk to spread to regional lymph nodes. The use of sentinel lymph node biopsy (SLNB) could be a promising procedure to assess this risk in clinically N0 patients. Metastatic SNs have been observed in 4.5-28% SCC (according to risk factors), in 9-42% MCC, and in 14-57% PEM. We observed overall 30.8% positive SNs in 13 consecutive patients operated for high-risk nonmelanoma skin cancer between 2002 and 2011 in our institution. These high rates support recommendation to implement SLNB for nonmelanoma skin cancer especially for SCC patients. Completion lymph node dissection following positive SNs is also a matter of discussion especially in PEM. It must be remembered that a definitive survival benefit of SLNB in melanoma patients has not been proven yet. However, because of its low morbidity when compared to empiric elective lymph node dissection or radiation therapy of lymphatic basins, SLNB has allowed sparing a lot of morbidity and could therefore be used in nonmelanoma skin cancer patients, even though a significant impact on survival has not been demonstrated.

Does this child have a foreign body aspiration?

Context: Foreign body aspiration (FbA) is a serious problem in children. Accurate clinical and radiographic diagnosis is important because missed or delayed diagnosis can result in respiratory difficulties ranging from life-treatening airway obstruction to chronic wheezing or recurrent pneumonia. Bronchoscopy also has risks and accurate clinical and radiographc diagnosis can support the decision of bronchoscopy. Objective: To rewiev the diagnostic accuracy of clinical presentation (CP) and pulmonary radiograph (PR) for the diagnosis of FbA. There is no previous rewievMethods: A search of Medline is conducted for articles containing data regarding CP and PR signes of FbA. Calculation of likelihood ratios (LR) and pre and post test probability using Bayes theorem were performed for all signs of CP and PR. Inclusion criteria: Articles containing prospective data regarding CP and PR of FbA. Exclusion criteria: Retrospectives studies. Articles containing incomplete data for calculation of LR. Results: Five prospectives studies are included with a total of 585 patients. Prevalence of FbA is 63% in children suspected of FbA. If CP is normal, probability of FbA is 25% and if PR is normal, probability is 14%. If CP is pathologic, probability of FbA is 69-76% with presence of cough (LR = 1.32) or dyspnea (LR = 1.84) or localized crackles (LR = 1.5). Probability is 81-88% if cyanosis (LR = 4.8) or decreased breaths sounds (LR = 4.3) or asymetric auscultation (LR = 2.9) or localized wheezing (LR = 2.5) are present. When CP is anormal and PR show mediatinal shift (LR = 100), pneumomediatin (LR = 100), radio opaque foreign body (LR = 100), lobar distention (LR = 4), atelectasis (LR = 2.5), inspiratory/expiratory abnormal (LR = 7), the probability of FbA is 96-100%. If CP is normal and PR is abnormal the probability is 40-100%. If CP is abnormal and PR is normal the probability is 55-75%. Conclusions: This rewiev of prospective studies demonstrates the importance of CP and PR and an algorithm can be proposed. When CP is abnormal with or without PR pathologic, the probability of FbA is high and bronchoscopy is indicated. When CP and PR are normal the probability of FbA is low and bronchoscopy is not necessary immediatly, observation should be proposed. This approach should be validated with prospective study.

Intraoperative training on the techniques of sentinel node biopsy in breast cancer

Principles: Surgeon's experience is crucial for proper application of sentinel node biopsy (SNB) in patients with breast cancer. A 20-30 cases learning curve of sentinel node (SN) and axillary lymph node dissection (ALND) was widely practiced. In order to speed up this learning curve, surgeons may be trained intraoperative by an experienced surgeon. The purpose of this report is to evaluate the results of this procedure. Methods: Patients with one primary invasive breast cancer (cT1-T2[<3 cm]cN0) underwent SNB based on lymphoscintigraphy using technetium Tc 99m colloid, intraoperative gamma probe detection, with or without blue dye mapping. This was followed by completion ALND when SN was positive or not found. SNB was performed by one experienced surgeon (teacher) or by 10 junior surgeons trained by the experienced surgeon (trainees). Four groups were defined: (i) SNB with immediate ALND for the teacher's learning curve, (ii) SNB by the teacher, (iii) SNB by the trainees under the teacher's supervision, and (iv) SNB by the trainees alone. Results: Between May 1999 and December 2007, a total of 808 évaluable patients underwent SNB. The SN identification rate was 98% in the teacher's group, and 99% in the trainees' group (p = 0.196). SN were positive in respectively 28% and 29% of patients (p = 0.196). The distribution of isolated tumor cells, micrometastases and metastases was not statistically different between the teacher's and the trainees' groups (p = 0.163). Conclusion: These comparable results confirm the success with which the SNB was taught. This strategy avoided the 20-30 SNB followed by immediate ALND early required per surgeon.

Fine structure of the vaccinia virus gene encoding the precursor of the major core protein 4 a.

A 6008 base pair fragment of the vaccinia virus DNA containing the gene for the precursor of the major core protein 4 a, which has been designated P4 a, was sequenced. A long open reading frame (ORF) encoding a protein of molecular weight 102,157 started close to the position where the P4 a mRNA had been mapped. Analysis of the mRNA by S1 nuclease mapping and primer extension indicated that the 5' end defined by the former method is not the true 5' end. This suggests that the P4 a coding region is preceded by leader sequences that are not derived from the immediate vicinity of the gene, similar to what has been reported for another late vaccinia virus mRNA. The sequenced DNA contained several further ORFs on the same, or opposite DNA strand, providing further evidence for the close spacing of protein-coding sequences in the viral genome.

Lymphome surrénalien primaire bilatéral [Primary bilateral adrenal lymphoma]

When abdominal imaging reveals the existence of unsuspected adrenal masses, a diagnostic strategy is necessary. We report the case of a woman presenting with pulmonary embolism, in whom abdominal ultrasound revealed voluminous masses in both adrenals without clinical or biological signs of hormone hypersecretion, but with mild primary adrenal failure. From a CT scan-directed needle biopsy of the right adrenal mass and subsequent staging we were able to diagnose a primary bilateral adrenal lymphoma, diffuse large B-cell type (REAL/WHO). On CHOP chemotherapy both adrenal masses decreased dramatically and the patient is in remission 18 months later. Primary adrenal lymphoma is a rare condition, since 65 cases have been reported to date. Histological diagnosis is nevertheless important, in view of the excellent response to specific therapy observed in some cases.

An ultrastructural approach to analogies between fungal structures and needle fibre calcite

Needle fiber calcite (NFC) is an ubiquitous terrestrial secondary calcium carbonate mineral often associated with calcitic nanofibers. NFC's origin has been debated for a long time and a fungal origin is often proposed. Fungi are known to be involved in mineral weathering and production of metal oxalate, but little information exists regarding the genesis of other minerals, such as calcite. In this study, a comparison of similar ultrastructural characteristics of fungal hyphae and NFC has been performed to highlight analogies between both features. These analogies clearly demonstrate the probable close relationship between fungal filaments (hyphae and rhizomorphs) and NFC and its associated nanofibers.