Radiation response assessment of organoids derived from patients with pancreatic cancer.

Background: The effectiveness of radiotherapy for pancreatic cancer is debated. Patient-derived organoids (PDOs) already mimicked clinical radiation response in other cancer types, which could be valuable in pancreatic cancer as well. This study aimed to investigate whether PDOs can be used to model RT response in pancreatic cancer and to explore the presence of a dose-response correlation. Methods: PDOs derived from two pancreatic cancer patients (HUB-08-B2-022A and HUB-08-B2-026B) were irradiated with doses ranging from 0 to 40 Gray. Viability assessments were conducted after seven and 10 days by measuring ATP-levels. Results were normalized, defining the viability at 0 Gray as 100 % and an absolute viability of 0 as 0 %. The relative area under the curve (rAUC) was calculated (0 = total sensitivity, 1 = total resistance). Results: With a readout time of seven days, both HUB-08-B2-022A and HUB-08-B2-026B exhibited viability above 50 % at the highest dose of 12 Gy (rAUC of 0.79 and 0.69, respectively). With a readout time of 10 days, both PDOs showed a dose-response relation although HUB-08-B2-022A was more sensitive than HUB-08-B2-026B (rAUC of 0.37 and 0.51, respectively). Increasing the radiation dose to 40 Gy did not further affect viability, but the dose-response relation remained present (rAUC of 0.13 and 0.26, respectively). In the final experiment with a readout time of 10 days and a maximum dose of 14 Gy, the dose-response correlation was paramount in both PDOs (rAUC 0.28 and 0.45, respectively), with HUB-08-B2-022A being most sensitive. Conclusions: In this setup, both pancreatic cancer PDOs showed an irradiation dose-response correlation. These preliminary findings suggest that pancreatic cancer PDOs are suitable for assessing radiation response in vitro. Further experiments are needed to eventually simulate treatment responses to personalized treatment strategies.

Bringing online adaptive radiotherapy to a standard C-arm linac.

Current online adaptive radiotherapy (oART) workflows require dedicated equipment. Our aim was to develop and implement an oART workflow for a C-arm linac which can be performed using standard clinically available tools. A workflow was successfully developed and implemented. Three patients receiving palliative radiotherapy for bladder cancer were treated, with 33 of 35 total fractions being delivered with the cone-beam computed tomography (CBCT)-guided oART workflow. Average oART fraction duration was 24 min from start of CBCT acquisition to end of beam on. This work shows how oART could be performed without dedicated equipment, broadening oART availability for application at existing treatment machines.

MR-OCTAVIUS 4D with 1500 MR and 1600 MR arrays is suitable for plan QA in a 1.5 T MRI-linac.

To ensure the accuracy of radiation delivery to patients in a 1.5 T MRI-linac, the implementation of quality assurance (QA) devices compatible with MR technology is essential. The OCTAVIUS 4D MR, made by PTW (Freiburg, Germany) is designed to ensure consistent and ideal alignment of its detectors with the direction of each beam segment. This study focuses on investigating the fundamental characteristics of the detector response for the OCTAVIUS Detector (OD) 1500 MR and OCTAVIUS 1600 MR when used in the MR-compatible OCTAVIUS 4D. Characteristics examined included short-term reproducibility, dose linearity, field size dependency, monitor unit (MU) rate dependency, dose-per-pulse dependency, and angular dependency. The evaluation of OD 1500 MR also involved measuring 25 clinical treatment plans across diverse target sizes and anatomical sites, including the liver/pancreas, rectum, prostate, lungs, and lymph nodes. One plan was measured with the standard setup and with a 5 cm left offset. The OD 1600 MR was not available for these measurements. The capability of the OD 1500 MR to identify potential errors was assessed by introducing a MU and positional shift within the software. The results demonstrated no significant differences in short-term reproducibility (<0.2%), dose linearity (<1%), field size dependency (<0.7%for field sizes larger than 5 cm × 5 cm), MU rate dependency (<0.8%), dose-per-pulse dependency (<0.4%) and angular dependency (standard deviation<0.5%). All tests of clinical plans were successfully completed. The OD 1500 MR demonstrated compatibility with the standard 95% pass rate when employing a global 3%/3 mm gamma criterion, and a 90% pass rate using a global 2%/2 mm gamma criterion. The detector demonstrated the capacity to measure treatment plans with a 5 cm left offset. With the standard parameters, the gamma test was sensitive to position errors but required an addition tests of mean/median dose or point dose in order to detect small dose difference.

Dramatic Increase in Incidence of Ulcerative Colitis and Crohn's Disease (1988-2011): A Population-Based Study of French Adolescents.

OBJECTIVES: Few data are available to describe the changes in incidence of pediatric-onset inflammatory bowel disease (IBD). The aim of this study was to describe changes in incidence and phenotypic presentation of pediatric-onset IBD in northern France during a 24-year period. METHODS: Pediatric-onset IBD (<17 years) was issued from a population-based IBD study in France between 1988 and 2011. Age groups and digestive location were defined according to the Paris classification. RESULTS: 1,350 incident cases were recorded (8.3% of all IBD) including 990 Crohn's disease (CD), 326 ulcerative colitis (UC) and 34 IBD unclassified (IBDU). Median age at diagnosis was similar in CD (14.4 years (Q1=11.8-Q3=16.0)) and UC (14.0 years (11.0-16.0)) and did not change over time. There were significantly more males with CD (females/males=0.82) than UC (females/males=1.25) (P=0.0042). Median time between onset of symptoms and IBD diagnosis was consistently 3 months (1-6). Mean incidence was 4.4/105 for IBD overall (3.2 for CD, 1.1 for UC and 0.1 for IBDU). From 1988-1990 to 2009-2011, a dramatic increase in incidences of both CD and UC were observed in adolescents (10-16 years): for CD from 4.2 to 9.5/105 (+126%; P<0.001) and for UC, from 1.6 to 4.1/105 (+156%; P<0.001). No modification in age or location at diagnosis was observed in either CD or UC. CONCLUSIONS: In this population-based study, CD and UC incidences increased dramatically in adolescents across a 24-year span, suggesting that one or more strong environmental factors may predispose this population to IBD.

[Granulocytic sarcoma, a diagnostic challenge: 3 pediatric cases]. / Le sarcome granulocytaire, un diagnostic à connaître : à propos de 3 observations pédiatriques.

Granulocytic sarcoma (GS) is a rare extramedullary tumor frequently associated with acute myeloblastic leukemia (AML). We report 3 cases of pediatric granulocytic sarcomas with various locations: skin, orbit, and bowel. Cases 1 and 2 were associated with AML; case 3 was isolated. In all 3 cases, the diagnosis was delayed or initially missed. Pathology and immunohistochemistry data identified the disease. GS is treated with chemotherapy, like AML. The prognosis of GS seems better than that of isolated AML.

Care protocol for persistent vegetative states (PVS) and minimally conscious state (MSC) in Lorraine: retrospective study over an 18-year period.

OBJECTIVES: Retrospective analysis of the efficiency of a protocol for care of chronic vegetative states (CVS) and minimally conscious state (MCS) in Lorraine. MATERIAL AND METHOD: Two indicators are used: protocol activity (number of patients hospitalized between 1988 and 2006, number of admissions per year, of requests per year, origin of requests, waiting time) and the epidemiological data (age, sex ratio, etiology, length of stay, geographic origin, number of deaths, number of hospital discharges). The number of CVS and MCS and patients having progressed towards arousal is specified as well as the technical procedures (orthopedic surgery, number of tracheotomies). RESULTS: Forty-seven patients (30 males and 17 females) were hospitalized in a 12-bed unit. The number of admissions per year was 2.4, and the annual number of requests varied between five and 15. Hospitalization times ranged from six to 18 months. The average length of hospitalization was 41 months. Eighty-eight percent of the cases were residents of Lorraine. The etiology was traumatic (53%), vascular (38% including 12% anoxia), miscellaneous (9%). Fifteen percent rate of return to arousal (average time period: 28.41 months, traumatic etiology) with hospital discharge in four cases. CONCLUSION: The protocol is managed as part of a local scheme and enables an appropriate response to a specific clinical profile by providing up-to-date multidiscipline follow-up care and a rapid solution should intercurrent events occur (signs of arousal, orthopedic deterioration, change of environment). Typical limitations are geographical remoteness and difficulties with family support care.

[Disseminated nocardiosis in a child with acute lymphoblastic leukemia]. / Nocardiose viscérale disséminée chez un enfant atteint de leucémie aiguë lymphoblastique.

Nocardiosis is a rare infectious disease in children. We report here a disseminated nocardiosis in a child with acute lymphoblastic leukemia. The patient presented prolonged febrile neutropenia and nodular pneumopathy. Based on the amplification of a 16S rDNA, a PCR assay detected Nocardia sp. in the patient's bronchoalveolar lavage (BAL) fluid. Culture of BAL samples yielded Nocardia nova colonies after 2 weeks of incubation. Hepatic, splenic, renal and cerebral localisations were detected on extension checkup. trimethoprime-sulfamethoxazole and amikacine were started given the results of PCR assay, with a good response. Improvement of the patient's general condition led to complete chemotherapy under ciprofloxacine and ceftriaxone treatment, without nocardiosis reactivation. Nocardiosis is a rare complication in children with acute lymphoblastic leukemia. trimethoprime-sulfamethoxazole prophylaxis is widely used to prevent Pneumocystis jiroveci infection in children with haematologic malignancies. As Nocardia species are usually sensible, trimethoprime-sulfamethoxazole could play a role in Nocardia prophylaxis in such population. In our patient, compliance with trimethoprime-sulfamethoxazole had been low. Nocardia species are relatively fastidious growth bacteria and are difficult to isolate with classical bacteriological techniques. Molecular methods are now available, with a good sensitivity and fast results allowing to start an appropriate antibiotherapy before culture results, as early treatment is a major prognosis factor in nocardiosis. Nocardia infection should be suspected in case of nodular pneumopathy in immunocompromised children. An extension checkup should be performed to detect secondary localisations.

Overexpression of the antiapoptotic gene Bfl-1 in B cells from patients with familial systemic lupus erythematosus.

Genetic determinants taking part in the development of systemic lupus erythematosus (SLE) are complex and not fully characterized. Dysregulated expression of genes involved in the control of apoptosis has been previously suggested. We report here a consanguineous family with SLE manifestations in three siblings associated in one of them with severe lymphoproliferative features. Laboratory studies showed no defect in CD95-mediated cell death. Screening expression of Bcl-2 family genes that regulate mitochondrial apoptosis pathway showed an overexpression of the antiapoptotic Bfl-1 gene. Real time RT-PCR analysis indicated that overexpression of Bfl-1 was restricted to B-cells, with normal expression in T-cells. Those results suggest that overexpression of Bfl-1 could result in impaired B-lymphocyte homeostasis and inappropriate immune response leading to autoimmune manifestations.

Effects of dietary fructose on liver steatosis in overfed mule ducks.

Overfeeding of some waterfowl species results in obesity, which is mainly characterized by a dramatic hepatic steatosis induced by strong accumulation of lipids synthesized from dietary glucose in the liver. In mammals, fructose is known to be able to raise plasma triacylglycerol concentrations significantly; consequently, this may induce obesity. The aim of this study was to assess the effect of partial replacement of dietary glucose provided by corn starch with fructose on metabolism and fatty liver production in the Mule ducks. On the basis of 9.5 kg maize (132,920 kJ) given twice a day for 14 days, a supplementation of 9,800 kJ was provided in form of glucose, sucrose or high fructose corn syrup (HFCS: 50 % glucose, 42 % fructose and 8 % other saccharides). Fatty liver weight in ducks fed with glucose supplementation was 499 +/- 21 g. Sucrose or HFCS supplementation brought about a significant increase in liver weight (+ 18.7 % and + 16.3 % vs. glucose supplementation respectively, p < 0.05). These results suggest that the dietary fructose favors the liver steatosis by increasing hepatic lipogenesis. Postprandial plasma insulin concentrations were similar in ducks fed diets with or without fructose, suggesting that the effect of fructose on liver steatosis is not mediated by insulin.

Pancreatic hormonal and metabolic responses in overfed ducks.

When overfed at their maximum (intensive overfeeding) or at only 80% (moderate overfeeding) of food intake capacity, Mule ducks developed strong liver steatosis, whereas Pekin ducks showed very marked extrahepatic fattening. During overfeeding, evolution of plasma glucose and triacylglycerol concentrations suggested a very strong increase in the hepatic lipogenesis as well as genotype- and diet-independent lipoprotein secretion. In contrast, lipoprotein-lipase activity was dependent on alimentary status (the intensive overfeeding induces the highest activities), and Pekin ducks showed higher lipoprotein-lipase activity than Mule ducks, which could favor extrahepatic fattening to the detriment of hepatic steatosis. In Pekin ducks, plasma pancreatic hormone concentrations are related to diet levels and blood sugar. With similar food intake, Mule ducks (moderately overfed) showed global blood insulin lower than that of Pekin ducks (intensively overfed) despite similar blood sugar levels, suggesting a trend towards reduced pancreas response to glucose in Mule ducks. This may result from their lower lipoprotein-lipase activity as previously shown in these two ducks overfed at only 60% of their maximal food intake capacity (unpublished results). These results suggest that high plasma insulin concentrations may be necessary to induce an optimum lipoprotein-lipase activity in overfed ducks.

Parametric and resonant transition radiation in periodic stratified structures.

We consider the problem of electromagnetic emission when an electrically charged particle crosses a periodically stratified structure following an arbitrary linear trajectory. A theory generalizing a recently developed method [Phys. Rev. E 63, 016613 (2001)] is presented in the framework of the classical theory of electromagnetism in continuous media. It allows one to account for both the so-called parametric radiation and the resonant transition radiation. We implement our model to interpret the experiments performed by Kaplin et al. [Appl. Phys. Lett. 76, 3647 (2000)] in the x-ray domain with a stack of 300 W/B(4)C bilayers irradiated by 500 MeV electrons.

Temporary phantom limbs evoked by vestibular caloric stimulation in amputees.

OBJECTIVE: Relationships between the vestibular system and the body schema have been suggested but never demonstrated in amputees. We studied the effects of vestibular stimulation on body representation in amputees focusing on the phantom limb phenomenon. METHOD: Prospective study in 31 amputated subjects of one or several limbs before the age of 16 years. The amputees underwent a caloric vestibular stimulation test, ipsilateral (n = 31) and contralateral (n = 8) to the side of amputation. Amputees were asked to report their perceptions spontaneously and to answer open questions. Four types of perceptions were analyzed: normal phantom, deformed phantom, painful phantom, and no phantom, before, during, and after the vestibular stimulation test. Data were compared between the two groups for pre- and post-test perceptions (chi2 test). RESULTS: Vestibular caloric stimulation provoked temporary perception of a normal phantom limb in 16 of 17 amputees who previously did not experience phantoms. For 12 of 12 amputees who currently experienced deformed or painful phantom limbs, caloric stimulation led to temporary replacement of the abnormal phantom with a non-painful normal phantom. CONCLUSIONS: The phenomena observed: 1) throw light on assumed mechanisms controlling construction of static and dynamic engrams used to produce the body schema; 2) complete the neuromatrix theory proposed to explain the phantom limb phenomenon; and 3) suggest that the vestibular system triggers the procedure of reconstruction of the global body schema.

Classical theory of resonant transition radiation in multilayer structures.

A rigorous classical electromagnetic theory of the transition radiation in finite and infinite multilayer structures is presented. It makes the standard results of thin-film optics, such as the matrix formalism, accountable; it allows thus an exact treatment of the propagation of the waves induced by the electron. This method is applied to the particular case of the periodic structures to treat the resonant transition radiation (RTR). It is noted that the present theory gives, in the hard x-ray domain, results previously published. The reason for this approach is to make the numerical calculations rigorous and easy. The numerical results of our theory are compared to experimental RTR data obtained recently by Yamada et al. [Phys. Rev. A 59, 3673 (1999)] with a nickel-carbon multilayer structure.

A matricial theory of soft x-ray resonant transition radiation in periodic multilayer structures.

When a charged particle crosses an interface between two different materials, electromagnetic radiation called Transition Radiation is emitted. The spectrum of this radiation extends up to x-ray domain. The Resonant Transition Radiation (R.T.R.) can be observed with a periodic arrangement of interfaces. The R.T.R. in the soft x-ray range has been recently measured by K. Yamada and coll. with a Nickel-Carbon multilayer structure [1]. In this paper, a rigorous electromagnetic theory of the R.T.R in finite and infinite multilayer structures is developed using the matricial formalism and compared with the experimental quoted data [1].

[Illusions of body normality in amputees and paraplegic patients]. / L'illusion de normalité corporelle chez l'amputé et le paraplégique.

Phantom limbs in amputees, or body illusion in hemiplegics, have been the subject of wide ranging descriptions. The detected abnormalities involve morphological, postural and/or kinetic features. The aim of this prospective study carried out in 25 amputees and 10 adult paraplegics was to describe the typology of these perceptions. Data were collected from free and semi-directive investigations before and after caloric vestibular stimulation. Amputees and paraplegics perceived normal, deformed and painful body phantom segments, reffered perceptions and "normal limbs" which took on the request posture considering the general body position (illusion of body normality). This perception corresponds to an image of the body, such as it should be and not such as it is. In amputees, the limb follows the movements of the prothesis. These perceptions conform quite well reality so that the loss of the paralyzed limb is not perceived as a missing limb. This illusion of body normality should be distinguished from the normal phantom limb, characterized by a stronger perception of the lost limb compared with the other. In both amputees and paraplegics, vestibular stimulation can generate or modify phantoms limbs or body illusion and can abolish painful phantom limbs. The neuromatrix, which rebuilds body representations, could get its information from reorganized cortical areas (instantaneous body image), autobiographical engrams (painful phantoms limbs), or innate engrams (identity body schema) that, via congruence mechanisms, could be identified as a somatic reference, particularly for motor programming. This interpretation is compatible with current knowledge and suggests how amputees can easily use a prothesis.

[MRI and leg stump neuroma]. / IRM et névromes des moignons damputation des membres inférieurs.

OBJECTIVE: To describe RMI aspects of leg stump neuroma and to evaluate RMI scan interest for neuroma diagnosis and management. POPULATION AND METHOD: During a 2 years period, 224 amputated patients consulting for pain or prostetics problems were studied. In 10 cases, a characteristic pain leads to neurona diagnosis. This is described as a sensation of ascending or descending electric shock induced by the stimulation of an identified point with a reproducible topography. In all these cases, RMI scans were performed. In thirty two other cases, a RMI scan was performed to confirm a pathology (bursitis, bone abnormality) or in order to establish an etiologic diagnosis. Twelve neuromas were diagnosed. RESULTS: RMI scan showed a neuroma in the ten cases with a clinical suspicion and two asymptomatic neuromas were diagnosed out of the 32 patients without clinical suspicion. Medium delay between amputation and neuroma diagnosis is 11,6 year. In six cases, staking was modified and in six other cases, surgery was necessary. In aIl cases, clinical manifestations disappeared. Vanous RMI aspects ofneuromas are described and illustrated. Neuroma is observed on the extremity of a nerve that have a wavy aspect on its top. The neuroma is an oblong structure, with clear limits. There is an hyposignal with Ti sequence and variable signal with T2 and after gadolinium injection. DISCUSSION: RMI scan is a good way to diagnose amputee neuroma. It makes it possible to demonstrate the pathological character of the neuroma. It has to be performed when a neuroma is suspected. It enables to confirm the diagnosis and establish the exact topography and anatomic connection. Mechanical strains role as a factor of discovering the neuroma is discussed because of the concomitant evolution of associated lesions (bursitis, bone edema). Surgical repair takes place after correcting abnormal mechanical strains.

[Early surgery management of pelvic region pressure ulcers versus directed cicatrization in a population of spinal cord injured patients]. / Chirurgie précoce de l'escarre pelvienne versus cicatrisation dirigée dans une population de médullo-lésés.

OBJECTIVE: To estimate the benefit brought by an early surgery management of pelvis region pressure ulcers compared to medical processing in a population of subjects spinal cord disabled. MATERIAL AND METHOD: The studied population consist of 53 patients (62 pressure ulcers) divided into two groups: the group 1 includes 30 patients (34 pressure ulcers) presenting pressure ulcers stage III or IV (NPUAP scale) with early surgery management, included consecutively during a period of 2 years; the group 2 includes 23 patients (28 escarres) included in a retrospective way, with medical processing by the same team of care. The criteria of judgment are the delay of healing and the delay of delivery of the station sat in the armchair. RESULTS: In the group 1, the average delay of healing is of 42 days and the average delay of delivery for the armchair of 39 days. In the group 2 healing can be obtained only in 13 cases and in an average delay of 180 days. Differences are significant (p < 0.05). DISCUSSION - CONCLUSION: The originality of this study results in the comparison of two processing within two groups of patients having close demographic characteristics. It clearly shows the interest of the early surgery of the pelvic pressure ulcers comparing to medical processing and illustrates the requirement for a close cooperation between teams specialized in plastic surgery and teams specialized physical medicine.