Consolidation par Y-epratuzumab en fractionné dans le lymphome B diffus à grandes cellules : résultats préliminaires d’une étude de phase II

Purpose

A multicenter, non-randomized, on-going phase II study, promoted by the GOELAMS aims to evaluate the efficacy and safety of fractionated administration of ⁹⁰Y-epratuzumab (two injections 7 days apart) in consolidation therapy for patients older than 60 years with diffuse large B-cell lymphoma and large tumor mass who presented a complete response (CR), unconfirmed CR (uCR) or partial response (PR) after induction therapy with six courses of R-CHOP14. We report the preliminary results on 41 of the 75 enrolled patients.

Patients and method

Toxicity was evaluated according to NCI-CTC version 3. The CR and uCR rate and the rate of conversion of PR to CR/uCR 6 weeks after injections of ⁹⁰Y-epratuzumab were evaluated using IWRC criteria.

Results

Thirty-three patients received two injections of ⁹⁰Y-epratuzumab. The toxicity of ⁹⁰Y-epratuzumab was mainly hematologic, characterized by neutropenia grade 3/4 in 81.8% of patients and thrombocytopenia grade 3/4 in 78.8% of patients, reversible. Two patients (6.1%) had grade 3/4 non-hematologic toxicity. Six weeks after injection of ⁹⁰Y-epratuzumab, 40.0% of patients improved their response and the rate of CR/RCu was 83.9%.

Conclusion

These preliminary results show significant toxicity, but mainly hematologic, expected in consolidation. The response rate is encouraging and needs to be confirmed by sufficient number of inclusions and follow-up.     

Le site de Longgupo dans son environnement géologique et géomorphologique

On a regional scale, Longgupo is found within a karstic landscape of fenglin-ouvala developed in the Triassic limestones of the Yangtze platform. After several seasons, it is now possible to define and propose a scenario for the formation of the site. During one of the intense karstification phases during the Cretaceous or early Tertiary, karstic conduits were created deep in the substratum. In concert with these deep flows and by karstic collapse, a cave was created. With the start of Himalayan uplift during the Oligocene and Miocene, the beginning of fluvial cutting was reflected by the partial erosion of the upper sandstone formations and the creation of the Miaoyu Valley. This action opened the cave, which would later be occupied by the hominid groups that interest us here. Probably at the end of the Tertiary, the cave, open at the bottom of the valley slope and facing upstream, began to be filled with alluvial deposits from the valley. The basal deposits (C III 10 of the current stratigraphic sequence, levels 20-13 of the first sequence) begin with black clays; at the Plio-Pleistocene transition, deposits become clearly alluvial, increasingly marked by reworking of surface and karstic clays and by systematically coarser contributions. During the deposition period of archaeological complexes III/III’ (previously levels 12-6), karstic collapse appears to have still been active. During the Lower Pleistocene sensu lato, the coarse nature of the deposits becomes accentuated. The material of complex II (previously levels 5-2) is a deposit that is clearly heterometric and coarse, composed at the end mainly of gravels, pebbles and more or less rounded blocks in a clayey matrix. At the conclusion of this new stage, the cave was entirely filled and, purely and simply, disappeared from the landscape. As the valley deepened during the Middle and Upper Pleistocene, the Longgupo slope underwent profound changes, the last of the limestone blocks disappeared from the slope limit and the archaeological site was protected by the coarse breccias that carpeted the slope. The main cause for the sedimentation processes at the site of Longgupo is the hydrosystem of the Miaoyu he, although injections of karstic type sensu stricto cannot be excluded. All of the arguments effectively support alluvial deposition: pebbles, an alternation of coarse and clayey beds, systematic and repeated granulometric decrease. But the stratigraphic disposition was disturbed by deformations due to gravity and karstic origins; the alluvial sediments, rendered plastic by the high proportion of clayey beds, were deformed by gravity (deformation of beds, faults, slopes) following the direction of the slope and by karstic collapse along the two limestone walls north and south of the sites (in sub-parallel faults to the south and by circular aspiration to the north). To this is added a calcitic consolidation of the upper levels that made it difficult to excavate complex C II. The stratigraphic disposition of the archaeological levels at Longgupo is now well understood. It has thus been possible to collect samples for absolute dating, to be published soon.     

Tchernobyl : le vrai, le probable et le faux

The Japanese earthquake and tsunami drew attention worldwide to nuclear power plant accidents and associated health risks. Since Chernobyl 25 years ago, several studies were published and we now have precise information concerning the long-term health of the population living near nuclear power plants and also in different European countries. The authors hope to bring some answers to the key questions from the public concerning radioactive units used and their significance, the evaluation of the number of radio-induced cancers within the different countries of Europe, other eventual health effects and the problem of possible congenital anomalies. Finally, French public perception on nuclear risk is examined and the feedback of the Japanese experience is evoked.     

Le gisement acheuléen de plein air de La Garde (Loire). Remarques sur une série lithique acheuléenne entre Rhône et Loire

The lithic assemblage of La Garde offers the opportunity to observe a Final Acheulean series located in the Loire department (south-east France). The site was probably a multi-activity place asking large tools and flakes, according to the strategies used by humans. Three main categories of large bifacial tools mainly made of flint can be described, with a triangular or oval shape and with a transversal cutting edge. These tools are more bifacial-tools than bifaces through the kind of shaping and the retouches on the cutting edges. The Levallois flaking is associated to various other types of knapping. The site, located along a small valley, suggests a human circulating between the Saône-Rhône corridor and the interior basins of the Massif Central Mountains. The Rhodanian corridor yielded little evidence of Acheulean settlements while in the Centre of France, they are numerous. La Garde proves that systematic prospecting in this area will permit in future to complete the map of the Acheulean occupations in south-east France.     

Apport de la fusion d’images tomoscintigraphiques avec la tomodensitométrie X ou l’imagerie par résonance magnétique en pathologie osseuse : expérience du service de médecine nucléaire de Sfax

The aim of our study was to assess the contribution of image fusion of SPECT combined with computed tomography (SPECT-CT) or magnetic resonance imaging (SPECT-MRI) in our daily practice of bone scintigraphy. Seventeen patients underwent a SPECT image fusion, SPECT-CT or MRI in addition to conventional bone scintigraphy. These acquisitions are made separately with images stored in DICOM format. The fusion was operated after a manual coregistration of the images. Results show that in 35.29% of cases, the image fusion allowed to pinpoint the exact location of increased uptake seen on the whole body scan and/or on static images. In 35.29% of cases, the fusion has confirmed a diagnosis doubtful in planar imaging. In five patients, representing 29.41% of cases, the fusion has corrected a diagnosis. In one patient (5.88% of cases), the fusion has eliminated a false positive related to increased uptake visualized on the whole body scan. In two patients (11.11% of cases), the fusion has eliminated false negative of bone scan in one case and of MRI in the other case. Finally, in nine patients (50% of cases), the fusion has influenced the therapeutic management.     

La frontière entre le Châtelperronien et l’Uluzzien : analyse comparative des typologies lithiques sur la base des dernières découvertes

The end of the Middle Paleolithic sees the appearance of “transitional” industries, which emerge at the same moment as anatomical modern humans enter Europe. All these transitional industries come from a Mousterian background and are closely connected to late Neanderthals. Among these industries we find two traditions characterized by backed blade pieces in Western Europe: the Châtelperronian and the Uluzzian. Two big conditions have been defined to allow a comparison between these industries: a chronological continuity and a geographic link. The recent data allows a new comparison.     

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.     

Segmentation d’images synchronisées à la respiration en TEP/TDM : étude sur fantôme

The aim of this study is to evaluate the accuracy of segmentation method by adaptive threshold in gated respiratory PET/CT and to deduce their indications and limits. Different acquisitions with phantom allow to study effect of movement, size and tumor activity compared to environment. The validity domain of these techniques, based on optimal threshold, is accurate if the tumor size is superior to 17 mm and the amplitude in a cycle is inferior or equal to 7.5 mm. For patient exams, an acquisition synchronized allows, even in the worst case, to freeze enough displacement in a cycle in which the relative amplitude is the lowest. Threshold adaptive method are validated for gated acquisitions for homogeneous tumors and not subjected to partial volume effect. If tumor size is inferior to three times the spatial resolution of the system, a more complex approach has to be employed.     

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.     

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.     

Étude préliminaire des industries archaïques de faciès Oldowayen du site de Hummal (El Kowm, Syrie centrale)

The spring site of Hummal is located in Central Syria, near the village of El Kowm between the Euphrates basin and the desert steppe stretching from Palmyra to Deir-ez-Zor. In 1966 the well was noted in a survey as Bir Onusi and a short preliminary study was carried out at the beginning of the 1980s. Since 1997, the Institute for Prehistory and Archaeological Science of the University of Basel has undertaken a complete interdisciplinary research program of this major site under the direction of J.M Le Tensorer, supported by the Swiss National Science Foundation and associated with the Directorate General of Antiquities and Museums of Syria under the direction of S. Muhesen. The site of Hummal is a prominent mound at an artesian spring built out of the sediments, which piled up during the whole Quaternary. Tectonic faults in the bed rock enabled the underlying water in a karstic system to flow out into a dolina, which trapped lacustrine, limnic and aeolian sediments since the Oldest Pleistocene. The impressive stratigraphy – 20 m high – comprises 23 geological units preserving a great number of archaeological levels. It covers an extremely long period of time ranging from the Oldest Palaeolithic (Oldowan) to Upper Palaeolithic (Aurignacian) over more than a million years. This impressive Old and Middle Palaeolithic sequence comprises several layers of Oldowan-like assemblage (23-16), an Acheuleo-Tayacian complex (14-13), five layers of Yabrudian (12-8) at least four levels of Hummalian (7, 6c, 6b, 6a) and a thick sediment complex with 8 Mousterian layers, each of them liable to be subdivided into several sublayers. The lithic industry in the lowest levels of the Hummal sequence, associated with abundant remains of large mammals, can be characterized by non-modified, quite fresh flakes, with, once in a while, traces of use but never bearing intentional retouches. Theses flakes are found with pebble-tools: choppers, chopping-tools, polyhedrons, bolas and core-like artifacts. This assemblage is typical in a broad sense of archaic Palaeolithic whose debitage corresponds to mode 1. From a techno-typological point of view, this industry tallies quite well with the so-called Oldowan stage. It shows remarkable similarities with the oldest assemblages at Ubeidiya but, so far, with no occurrence of bifacial knapping. If the layers 17 and 18 of Hummal relate to this period dating back to 1.6 to 1.2 million years, these levels would be the oldest ones ever found in central Syria. However, as we have no absolute dating at our disposal so far, we will remain careful in assigning a chronological time span for these layers. For this area, from a stratigraphic point of view, the Oldowan levels of Hummal occur before the Acheulean and certainly before the Acheulean sequence of El Meirah (region of El Kowm) which is itself related to the period before Matuyama-Brunhes paleomagnetic reverse. Dating of the lowest sequence of Hummal is underway. If we take into account stratigraphic and techno-typological observations, we assume that the Oldowan-like levels of the site should be older than one million years at least. The sequence of Hummal is one of the largest in the Near-East. Therefore, it can be regarded as a key-site for world prehistory.     

Introduction à l’étude du site de Longgupo

The site of Longgupo, discovered in 1984, is located south of the crossing of the Three Gorges of the Yangtze, in the eastern part of Chongqing Province. Situated on the limestone slope of the Miaoyu Valley, three excavation campaigns have been carried out since 1985. The first two seasons took place from 1985–1988 and 1997–1998, directed by W.B. Huang and the last campaign from 2003–2006 by E. Boëda and Y.M. Hou. After the first two campaigns, the presence of several bones, with an estimated age of 1.9 My, notably including a mandible fragment attributed to a hominid² and the discovery of more than 20 lithic artifacts incited not only great interest in the scientific community, but controversy as well since these data contradicted diffusion models of the first hominids out of Africa. Paleoanthropological data often being privileged over other data, including lithic artifacts, the anthropic nature of the site was contested. Yet the few artifacts from the initial excavations irrefutably demonstrate their manufacture by humans, in particular those in exogenous stone. To definitively re-establish the authenticity of this site by applying the latest investigative methods, a new Franco-Chinese campaign was organized. The objective of the 2003–2006 field seasons focused on understanding and analysis of the archaeological data in their geomorphological and stratigraphic contexts.     

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.     

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.     

Perturbateurs endocriniens et maladies métaboliques

During the last decades, there has been a dramatic increase in the prevalence of metabolic diseases, diabetes and obesity, which may be primarily related to changes in diet, lifestyle and behaviour. However, because of the parallel increase in pollution, in the use of chemicals for a variety of purposes, in drug consumption and because of additional evidence showing the involvement of the endocrine system in the regulation of metabolism and body weight, scientists have suspected the implication of endocrine disruptors in the developments of these conditions and diseases. Experimental studies have shown a possible role of diethyl stilbestrol, bisphenol A and dioxins/PCBs in endocrine disruption and obesity and highlighted the importance of exposure during vulnerable states such as the perinatal period. Some epidemiological studies also supported the possible role of these pollutants in metabolic diseases and obesity. Obesity is known to alter the kinetics of persistant organic chemicals such as dioxins and PCBs. These pollutants are stored in the adipose tissue, which may protect other more sensitive organs. However, during drastic weight loss, these pollutants are released in blood and tend to delay the improvement in metabolic parameters that are usually observed following weight loss. In conclusion, certain pollutants appear to play a role in the development of metabolic diseases and obesity, although their relative contribution as compared to other risk factor is unknown. In addition, obesity and weight loss alter the kinetics of certains pollutants and their toxicity.     

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.     

Tumeur du scalp : mode révélateur rare de carcinome vésiculaire thyroïdien

Cutaneous metastases of thyroid follicular carcinoma are rare. A scalp metastasis revealing a thyroid cancer is exceptional. We report the case of a 70 year-old women who presented with a scalp tumor progressively increased. Morphological imaging disclosed an important cutaneous tumor in occipital region with osteolysis. Surgical resection of this tumor was performed and pathology identified a cutaneous metastasis of a thyroid follicular cancer. This case report illustrates a rare presenting sign of thyroid follicular cancer. Cutaneous metastases coexists with other metastases (bone or lung) and means and ominous prognostic factor for the evolution of thyroid follicular cancer.     

Perturbateurs endocriniens et troubles du comportement : non, nous n’avons pas encore tiré toutes les leçons de l’histoire du DES

Synthetic oestrogens such as diethylstilbestrol (DES) or 17-alpha-ethinylestradiol (EE) administered to pregnant women during numerous years were demonstrated as responsible of severe ravages for children. Regarding behavior disorders, works on mice or rat have shown the effects of these xeno-hormones used even at very weak dose, time of fetal exposition being crucial. Works are less numerous for humans but recent analysis of the spontaneous Hhorages cohort brings demonstrative data. Analogy between animal and man is discussed as well as the effects of bisphenol A and organophosphate pesticides.     

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.