Irathérapie génique anticancéreuse utilisant le NIS : une approche très prometteuse

The symporter Na/iodine (NIS) is a recently discovered membrane protein, recognized to be at the origin of accumulation of iodine in the thyroid, salivary glands, stomach and mammary glands during lactation. If its intrinsic property served as the basis for nuclear imaging and radiotherapy metabolic of differentiated thyroid cancers and their metastases, the cloning of its gene provides a powerful strategy for cytoreductive gene therapy, based on the targeted transfer of this last one in all types of cancer cells. Its expression gives the ability to these cells to accumulate iodine. The aim is to benefit from the advantages of radioiodine therapy (efficiency, reduced side effects) and to optimize the management of thyroid cancer. This approach offers an attractive therapeutic alternative for non-thyroidal cancers, especially in the context of a multimodal approach. Techniques and equipments necessary for the first clinical trials are already existing in the departments of nuclear medicine. The perspectives of clinical application, however, require a better knowledge of the regulation of expression and functionality of NIS. After a review of the biology of NIS, our work aims to recount the results of different tests that have demonstrated the benefits of this approach, its limitations and prospects for its improvement.     

Valeur pronostique du curage ganglionnaire prophylactique dans le cancer différencié de la thyroïde

Objective

Although the efficacy of total thyroidectomy as the first step in differentiated thyroid cancer (DTC) management is well proven, it is always a matter of controversy whether prophylactic lymph node dissection improves prognosis and survival in DTC patients without suspicion of lymph node metastases either clinically or radiologically. The aim of this work is to study relapse rates in patients according to the initial presentation and type of surgery performed, in order to analyze the prognostic impact of lymph node dissection.

Patients and methods

One hundred and thirty patients with DTC were classified according to clinical presentation and type of surgery performed. They were monitored for six years to watch for recurrence.

Results

In patients with no clinical evident lymph nodes, the relapse rate was lower among patients who underwent total thyroidectomy in one step with prophylactic lymph node dissection.

Conclusion

Based on the results of other studies, and on our department experience of thyroid cancer management and monitoring, we strongly advocate careful and systematic exploration of the central lymph node compartments with exploration of the lateral side of the lesion if in doubt.     

Mise en place d’une équipe d’experts en physique médicale au Luxembourg : organisation, résultats qualité et radioprotection en médecine nucléaire (2002–2011)

Implementations of the statutory UE requirements concerning ionizing radiation in the medical domain (96/29/Euratom, 13th May 1996; 97/43/Euratom, 30th June 1997) have changed quality control in medical imaging departments. In Luxembourg, the Ministry of Health and the “Union of Luxembourg Hospitals” have thus created a “Medical Physics Cell” (five Medical Physics experts). It is in charge of implementing a standardized program of Quality Assurance (QA) and radiation protection relative to patients as well as staffs, on a coordinated national basis, in all five in-hospital nuclear medicine departments of the country. The program distributes QA controls between three levels, various periodicities and degrees of expertise. It sensitizes staff and medical doctors by trainings and facilitates ISO accreditation. From 2002 to 2011, in all five in-hospital departments of nuclear medicine of a small country, image quality, radiation protection and reference values of each medical equipment were defined and implemented in a standard way. In 2011, the medical physics cell, the driving force leading to the institutionalization of the discipline within the nuclear medicine departments, is considered as a partner rather than as a control body by the teams in charge of the nuclear medicine departments.     

Radioactivité résiduelle avant vidange des cuves de décroissance de déchets liquides : bilan annuel d’un service de médecine nucléaire hospitalier au Luxembourg

Residual radioactivity within decay tanks in an in-hospital clinical nuclear medicine unit reflects the specific typology of the concerned unit. To learn how to improve management of emptying the tanks, measures of residual radioactivity over the year 2009 have been compared to prevailing legal norms in Luxembourg. Legal norms have in no case been outpassed. A minimal residual radioactivity, below legal thresholds, has been often found (84%). It concerned ¹³¹I, ^99mTc and ¹¹¹In. This is why management of radioactive decay tanks may be continued unchanged.     

Apport de l’imagerie hybride TEMP-TDM dans le suivi d’un cancer différencié de la thyroïde

In the management of patients with differentiated thyroid cancer (DTC), abnormalities detected on planar whole body scan and ¹³¹I-SPECT are difficult to interpret because of a lack of anatomical landmarks and limited specificity. Integrated ¹³¹I-SPECT-CT imaging has an additional value for characterization of equivocal tracer uptake seen on planar imaging as well as for precise localization. We illustrate through an observation the incremental diagnostic value of ¹³¹I-SPECT-CT images in the diagnosis of a cervical lymph node mimicking a physiological uptake on planar views. A 35-year-old Tunisian female was followed for papillary thyroid carcinoma, for which she underwent total thyroidectomy and iratherapy. Three years after a complete remission, the thyroglobulin (Tg) level on TSH stimulation increased. Diagnostic planar images with ¹³¹I did not disclose any obvious pathological foci. Furthermore, we noticed an increased ¹³¹I-uptake in the left sub-mandibulary area, which suggested a salivary physiological activity. SPECT-CT of the neck and chest were then performed with a Symbia T camera. Fused images demonstrate that this activity corresponds to a cervical lymph node closely adjacent to sub-mandibulary gland. Management of the patient was then changed. In selected patients with DTC, hybrid imaging should be used as a complementary to planar imaging in terms of diagnostic accuracy, because of superior focus localization and additional anatomic information derived from the CT component. Integrated SPECT-CT is then a useful tool, especially in cases of unclear diagnoses, precising anatomical localization of areas of increased ¹³¹I-uptake and distinguishing malignant lesions from normal physiological uptakes. This is particularly important in an oncologic center, as ours, where we don’t yet have a positron emission tomography (PET) camera is not yet available.     

Métastase rénale d’un carcinome vésiculaire de la thyroïde révélée par le balayage du corps entier à l’iode 131

Distant metastasis of differentiated thyroid carcinoma generally affect lung and/or bone tissue. Renal metastasis from thyroid carcinoma is extremely rare. We report a case of renal metastasis from a follicular thyroid carcinoma in a 55-year-old man, occuring 11 years after total thyroidectomy, fortuitously discovered on a whole body scan carried out after 131-iodine therapy for neck recurrence of disease. Salient features of our clinical case are the fortuitous mode of discovery the unilateral localization of metastases and especially the long time interval which separates its detection from that of the primitive tumour. This case report exemplifies the useful role of the whole body scan carried out after 131-iodine therapy better adapted to reveal often undetectable occult metastases with low dose, but also to ensure a regular and protracted follow-up of patients treated for differentiated thyroid carcinoma.     

Association hyperthyroïdie et cancer thyroïdien différencié (médullaire exclu). À propos de sept observations

The aim of this study was to draw attention to the fact that hyperthyroidism does not exclude the possibility of concurrent thyroid carcinoma. We analyzed the frequency and consequences of this association through seven cases of thyrotoxic patients with differentiated thyroid carcinoma followed by a review of literature.

Patients and methods

The nuclear medicine department of the CHU Ibn Sina has more than 3000 cases of differentiated thyroid carcinoma where 10 patients with association of hyperthyroidism could be retrieved. Our study focused on seven cases well documented and regularly followed. The main parameters collected were the following: age, sex, personal and family history of thyroid disease, clinical presentation, etiology of hyperthyroidism, preoperative paraclinical explorations, surgery performed, histopahological findings, complementary therapy and follow-up.

Results

Group included six females and one male, average age was 41.4 years. There were four cases of Graves’ disease, two cases of single toxic nodule and one case of functional multinodular goiter. All patients underwent total thyroidectomy. Final pathologic examination disclosed five papillary carcinomas and two follicular carcinomas. During 2 to 8 years follow-up, there was neither local recurrence nor metastasis.

Conclusion

The diagnosis of hyperthyroidism does not preclude concurrent thyroid carcinoma. Careful assessment of such patients is mandatory to exclude an associated thyroid malignancy particularly in the presence of a nodule in a hyperfunctioning thyroid.     

Étude de faisabilité du ganglion sentinelle dans le cancer de la prostate par cœlioscopie : premiers résultats

Objectives

The standard lymphadenectomy is currently a challenge in the management of prostate cancer. The aim of this prospective study was to evaluate the performance of the sentinel lymph node (SLN) by laparoscopy in patients with localized prostate cancer, candidates for local treatment.

Patients and methods

Patients were injected transrectal ultrasound-guided with 0.3 mL/100MBq 99^mTc-Sulfur rhenium colloid in each prostatic lobe, the day before surgery. Lymphoscintigraphy was performed after 2 hours. The detection was realized intraoperatively with a laparoscopic probe (Gamma Sup Clerad^®) followed by extensive dissection. Counts of SLN were performed in vivo and confirmed ex vivo. The histological analysis was performed by HPS staining and followed by immunochemistry if SLN was free.

Results

Seventy patients with carcinoma of the prostate at intermediate or high risk of lymph node metastases (D’Amico), PSA median 9.5 ng/mL [6–130], were included in the study. The lymphoscintigraphic detection rate was 94.2% (66/70) and intraoperative of 97.0% (68/70). Fourteen patients had lymph node metastases, six only in SLN. The false negative rate was 2/14 (14.0%). The internal iliac region is the first metastatic site (40.9%). Limited or standard lymph node dissection would have ignored respectively 72.7% and 59.0% of lymph node metastases.

Conclusion

The laparoscopy is adapted to a broad identification of SLN and targeted dissection of these lymph nodes significantly limits the risk of surgical extended dissection while maintaining the accuracy of the information.     

Fixations extra-osseuses du Tc MDP dans le cas d’un cancer du sein métastatique à l’os

Aim

To report and discuss an unusual visceral uptake on bone scan in a case of breast cancer with bone metastases.

Patient and methods

A 40-year-old woman, with untreated bilateral breast cancer was referred to our department for a bone scan.

Results

The bone scan evidenced multiple metastases over the axial skeleton. Uncommonly, visceral uptake was noted associating diffuse bilateral lung uptake and intense myocardium, stomach and kidneys uptakes. Serum calcium level was high: 4.08 mmol/L (normal: 2.38–2.70 mmol/L).

Conclusion

The incidental observation of metastasic calcifications on bone scan is often related to severe hypercalcemia. Such pattern should alert the physician on the existence and the severity of calcium metabolism disturbances that had not been suggested before.     

Threats to and conservation of North African wetlands: the case of the Ramsar site of Beni-Belaid (NE Algeria)

Because of their biogeographical and geomorphological context, the northeastern Algeria wetlands present high species and community richness. The vegetation study of the Ramsar site of Beni-Belaid (Kabylia) showed the existence of four main communities, distributed along gradients of hydrology and disturbance. The obtained results reveal worrying threats on short term: overgrazing results in the lake invasion by the sand eroded from the coastal dune; agriculture induces illegal cutting, water pollution and excessive groundwater pumping; finally, hunting and fishing are illegally practiced into the Ramsar site. The awareness of public authorities is needed in order: (1) to completely protect the wetland with the aim of restoring a riparian forest belt; and (2) to initiate a campaign for increasing the local population awareness, and its involvement in conservation programs.     

Ethical models underpinning responses to threats to public health: a comparison of approaches to communicable disease control in Europe

Increases in international travel and migratory flows have enabled infectious diseases to emerge and spread more rapidly than ever before. Hence, it is increasingly easy for local infectious diseases to become global infectious diseases (GIDs). National governments must be able to react quickly and effectively to GIDs, whether naturally occurring or intentionally instigated by bioterrorism. According to the World Health Organisation, global partnerships are necessary to gather the most up-to-date information and to mobilize resources to tackle GIDs when necessary. Communicable disease control also depends upon national public health laws and policies. The containment of an infectious disease typically involves detection, notification, quarantine and isolation of actual or suspected cases; the protection and monitoring of those not infected; and possibly even treatment. Some measures are clearly contentious and raise conflicts between individual and societal interests. In Europe national policies against infectious diseases are very heterogeneous. Some countries have a more communitarian approach to public health ethics, in which the interests of individual and society are more closely intertwined and interdependent, while others take a more liberal approach and give priority to individual freedoms in communicable disease control. This paper provides an overview of the different policies around communicable disease control that exist across a select number of countries across Europe. It then proposes ethical arguments to be considered in the making of public health laws, mostly concerning their effectiveness for public health protection.     

Analyse des artefacts lithiques du site de Longgupo

Excavation has enabled recovery of 854 artifacts within 30 archaeological levels in the south sector and 11 in the north (chapter 3). These levels are quite probably contemporaneous, or even the same. The quantitative disparity in the number of strata between the two sectors is simply due to the fact that only the lower half of the northern zone was completely investigated. Similarly, the number of artifacts recovered by level varies according to the surface area excavated, although is some cases the density of material is significant despite the small area excavated, for example stratum C IV 5 which contains 174 lithic artifacts in 2 m². Before undertaking the technological analysis of the artifacts, given the preceding polemics provoked by the great age of this site and its implications for the spread of the first populations out of Africa, it was deemed important to carry out a plurifactorial analysis combining all of the data related to: the stratigraphy, taphonomic processes (post-depositional disturbance), analysis of natural processes that may have produced eoliths, experimentation and techno-functional analysis of the material. The stratigraphy shows clear interstratifications of fine and coarse fluviatile levels with often very clear particle size sorting of the coarse fraction. The archaeological material is typically found at the interface of these strata, either at the base of a clayey matrix, overlying a preceding coarse level, or in the superficial part of a sandy-clay deposit underlying coarse deposits. Post-depositional disturbance revealed during the new excavations in 2003–2006 cannot alone be the cause of eoliths. Excavation of a 6 m² zone in the modern river bed, located below the site, has demonstrated that the technological traits of eoliths recovered cannot in any way be confused with the technological traits of the artifacts recovered at the site itself. Similarly, viewed quantitatively, the 6 m² zone excavated in the river bed yielded around 20 eoliths while the 30 m² zone excavated at the site yielded 854 artifacts, one stratum alone yielding 184 artifacts in a 3 m² zone. During the experimental phase, adopting the same conditions of procuring raw material, from the same river bed, we very quickly realized the rarity of types of adequate volume that had been generally used at the site and the need to use certain operational processes to create such a form. In addition, the hardness and presence of several natural fracture planes in the Triassic limestone explain the choice of different operational processes and the very high number of knapping accidents, including those occurring during bipolar percussion. Although 90% of the raw material used was cobbles or broken blocks of local Triassic limestone, 10% of the tools were made on exogenous raw materials – siliceous or gravelly limestone, quartzitic sandstone, chert, volcanic rock – that are absent from the immediate environment of the site. These raw materials were brought to the site in the form of tools: worked cobbles, large retouched flakes, backed double-truncated flakes, a plaquette with a lateral bifacial edge, etc. The 854 artifacts have been classified into six object classes: worked cobbles with transversal edge (39%), worked cobbles with lateral edge (2%), unipolar flakes (27%), bipolar objects (half-blocks, half-cobbles including some flat “split” cobbles, “orange slices”, flakes and diverse fragments) (17%) and fragments resulting from knapping of blocks or cobbles (13%), hammerstone (2%). When the frequencies of these classes are calculated for each of the sectors, percentages are similar, indicating a high degree of homogeneity in the archaeological assemblages at the site. The situation is somewhat different when assemblages are compared within a single sector. Slight differences appear in the percentages of bipolar pieces and unipolar flakes. These differences seem to be random, like the frequency rate of knapping accidents in bipolar reduction, or economic, such as the choice of operational schemes to create worked cobbles based on the availability of suitable raw materials. The technological affinity between each of the archaeological assemblages tends to demonstrate great stability in technological knowledge through time. The class of worked cobbles is by far the most important and, apart from a few flakes produced intentionally, it appears to group all of the tools. To avoid placing these tools in a restrictive, semantically meaningless, class, we prefer the concept of matrix to the term worked cobble. A matrix is a structured arrangement of a series of technological traits, in a form as close as possible to that of the future tool. The matrix phase leads to the tool production phase, which may be unnecessary if the matrix phase includes fictionalization. In other words, the concept of matrix enables separating the phase of preparing a predetermined volume, such as a blade, Levallois flake or bifacial piece, from the tool production phase, consisting in creating the type of transformative edge intended, if necessary. The tool is thus an artifact of a specific form with an integrated edge and an operational scheme both specific to the function attributed to it and means of use associated with the form. Observed variability relates to: the size of the volume ranging from to 20, morphology, the form of the line formed by the edge which can in frontal view be curved, linear, sinuous or denticulated, and in transversal view curved, linear, sinuous or saw-toothed, and the length of the edge ranging from 1 to 10. Matrices with a simple bevel are distinguished from double bevels. In the framework of the technological analysis of production schemes to produce matrices with a simple bevel, a broad range of variability in production schemes can be observed, divided arbitrarily into two stages. The first stage consists in creating as closely as possibly the technological traits of the future matrix due to five general schemes. The first scheme (A) consists in selecting a cobble or block naturally possessing at least some of the technological traits needed. The missing traits are added by various preparations, including bipolar percussion 3 times out of 5. The second scheme (B) consists in knapping a flake from the block with some of the technological traits required for the matrix present on one of its surfaces. The third scheme (C) consists in the choice of a plaquette from which a bipolar shock creates the main traits of the matrix. The fourth scheme (D) consists in choosing a volume very similar to the intended matrix. The fifth and final scheme (E) consists in knapping a flake with technological traits very different from those intended. Depending on the distance between intention and realization, a second stage may be necessary. In general, this second stage perfects or creates the intended active edge, which is rarely obtained in the first stage. To produce a matrix with a double bevel, it is sometimes necessary to add an intermediate stage in order to prepare the second bevel. The first stage remains the same, with the use of the five operational schemes. By contrast, a clear difference exists in the percentages for the use of these schemes. For a matrix with a simple bevel, scheme A is dominant, followed by scheme D, while the situation is reversed for a matrix with a double bevel, where scheme D is dominant. Unipolar flakes, representing 27% of the assemblage, are produced in three different ways. The most important is flakes resulting from matrix production. The two others are flakes produced during different knapping schemes, some flakes in relation to the few cores present, other flakes in exogenous raw materials produced elsewhere and generally much larger. The other classes are dominated by bipolar products resulting essentially from knapping accidents. To summarize, these assemblages are characterized by: the search for tools differentiated by form and active edges; more than 90% of the tools made on two kinds of supports: a matrix with a simple bevel or a double bevel; matrices obtained using different operational schemes successively associating if necessary a knapping stage and a shaping stage. While the Triassic limestone is hard and thus imposes a strong constraint on knapping, the range of operational schemes appears to have been a “cultural” response diversified to this constraint and the presence of tools on exogenous raw materials. At the scale of China, comparison of this industry is impossible since it is the only site of this age and to contain so much material. The site of Majuangou, the only site of similar caliber, is younger by several hundred thousand years and is located several thousand kilometers to the north, making comparisons meaningless. We note only that most of the tool supports at Majuangou are knapped flakes. On an inter-continental scale, the comparison of sites of equal age is more promising. But lithic analyses are based on different methods, preventing comparison of similar data. However, if we make a simple summary of the data available, we can first say that in Africa, during these periods, different development technological stages were present and stages that are considered more evolved are manifestly less common using our approach. While these stages are more or less contemporaneous, which counters the idea of uniqueness, they would more surely be evidence of populations that were not in direct contact and had separate lines of development. In Asia, the Longgupo industry evidences a different technological option than that of contemporaneous populations in Africa. By contrast, when we take into account its developmental stage, we realize that this is an “evolved” stage in which the form of the support of the future tool is predominant. If we compare Africa and Asia in terms of stages, we are a priori at the same stage with different options being selected.     

Plastid-to-nucleus signalling

The function of the eukaryotic cell depends on the reciprocal interaction between its different compartments. Plastids emit signals that regulate nuclear gene expression to ensure the stoichiometric assembly of plastid protein complexes and to initiate macromolecular reorganisation in response to environmental cues. It is now clear that several different plastid processes produce signals that influence the expression of photosynthetic genes in the nucleus. The genome uncoupled (gun) mutants recently revealed one of the plastid signals, the chlorophyll intermediate Mg-protoporphyrinIX.     

Reward representations and reward-related learning in the human brain: insights from neuroimaging

This review outlines recent findings from human neuroimaging concerning the role of a highly interconnected network of brain areas including orbital and medial prefrontal cortex, amygdala, striatum and dopaminergic mid-brain in reward processing. Distinct reward-related functions can be attributed to different components of this network. Orbitofrontal cortex is involved in coding stimulus reward value and in concert with the amygdala and ventral striatum is implicated in representing predicted future reward. Such representations can be used to guide action selection for reward, a process that depends, at least in part, on orbital and medial prefrontal cortex as well as dorsal striatum.     

Selected problems with phenol toxicity

Some data on the toxicity of phenol are surveyed. Environmental and health hazards are discussed. Pending standards are given. These are 0.3-19 mg/m3 in the air and working places in different countries. Acceptable phenol concentration in the air is 10 mg/m3 in Poland. The same standard for public buildings is 0.012 mg/m3. Toxic effects of phenol were reported in case of occupational exposition to 5 mg/m3 of air. Data concerning urine levels of phenol in children living in the buildings of increased phenol levels in the air and health impact of this are discussed.     

Neural control of human motor development

It has been possible to expand considerably our understanding of human motor development by making a detailed analysis of various types of movement and muscular activation patterns during different stages of development. Alterations in development subsequent to the appearance of brain lesions have enabled valuable information to be collected about the underlying neural mechanisms, in addition to new information concerning the pathophysiology of cerebral palsy. Studies on the development of the corticospinal system indicate that plastic changes can take place after perinatal brain damage.     

Prise en charge des cancers de la prostate : points de vue du radiothérapeute

In 2011, the prostate cancer positions itself clearly like a problem of public health. The radiotherapy has shown these twenty last years significant improvements with the advent of the three-dimensional conformation radiotherapy as a standard in the treatment of the adenocarcinoma prostate cancer, and now with the contribution of the modulation of intensity which makes it possible to consider an increment of amount on estimated target volume without toxicity added to the organs at risks. Radio-hormonotherapy association for high-risk cancers also went to current practice. The nuclear medicine through new tracers and new indications probably will allow the experts dealing with these patients to better define the indications and to better distinguish the patients who will profit authentically from a therapeutic strategy more than of another, and even to associate them…     

Données stratigraphiques, archéologiques et insertion chronologique de la séquence de Longgupo

The site of Longgupo is located north of the subtropical zone and is part of the domain of eastern fauna. The large number of mammal species identified at this site enables clarification of the broad pattern of paleoenvironmental change for the three assemblages from the first stratigraphic sequence (Huang W.-B. excavations). The different species have been classified in four biogeographic groups: subtropical (moderate monsoon), tropical forest (hot and humid climate), montane (cold climate) and prairie (cold and dry climate). Variation in the representation rate of each of these groups enables general reconstruction of the paleoenvironments for the three assemblages identified at Longgupo: a lower assemblage in a hot and humid climate with cold and dry episodes, an intermediate assemblage in a rather cold and dry climate in the lower part, becoming progressively warmer and humid toward the top of the sequence with a monsoon influence more marked than the present day, and an upper assemblage in a rather cold and dry climate. This biochronology and general paleoenvironmental reconstruction are clearly important, but as mentioned above, the stratum by stratum correspondence between the old and new stratigraphic sequences has been quite difficult because the position of material recovered during the early excavations was not recorded.     

Traitement de l’hyperthyroïdie par l’iode 131 : à propos de 280 cas

We report through this work the experience of nuclear medicine department at Ibn-Sina hospital (Rabat), in the treatment of hyperthyroidism with iodine-131. We retrospectively studied a cohort of 280 patients with hyperthyroidism, from several regions of Morocco between January 2001 and January 2010. A clinical examination and a serum assessment of TSHus, FT4 and FT3 have been made at baseline and at 3, 6, 12 and 24 months after radioiodine therapy. The activity of iodine-131 administered ranged from 296 to 740 MBq and depended on the pathology being treated, age, thyroid volume, intensity of clinical and biological hyperthyroidism and socioeconomic situation. Radioiodine therapy has often been proposed as a treatment for second or third intention, 71 patients were initially treated with iodine-131, while 209 patients had received iodine-131 after failure of medical treatment and/or recurrence after surgical treatment. Graves’ disease was the most common etiology (60%), followed by toxic adenoma (20%), and multinodular toxic goiter (13%). The therapeutic efficacy of a single dose of radioiodine evaluated after a 6-months follow-up was 92% in Graves’ disease, 98% in toxic adenomas and 97% in toxic multinodular goiter. No acute complication was observed. Taking into account our socioeconomic context, radioiodine therapy remains the preferred treatment of hyperthyroidism in our country with good value vs. price and excellent tolerance.