Monte Carlo dose calculations of shielding disks with different material combinations in intraoperative electron radiation therapy (IOERT).

PURPOSE: Shielding disks play an important role in intraoperative electron radiation therapy, and different designs are currently used in clinical practice. This paper investigates the dosimetric impact of the shielding disk used during intraoperative electron radiation therapy (IOERT). MATERIALS AND METHODS: This paper focuses on the study of four shielding disks types that have been used in our clinic: Aluminum (Al)/Lead (Pb), PMMA/Copper(Cu)/PMMA, Aluminum (Al)/Copper (Cu) and Aluminum (Al)/Steel with their specific thicknesses. The theoretical study was conducted with the EGSnrc Monte Carlo (MC) code. On the other hand, the measurements were carried out with gafchromic films for the four shielding disks for the same setup inside the water phantom. Finally, a comparison of the simulated and measured PDD curves was performed for the four material combinations. RESULTS: MC simulation and gafchromic measurements illustrated that dose values under the four shielding disks types were close to 0, whereas the backscattering enhancement of the disks were 103% with Al/Pb shielding disk, 102% with Al/Steel shielding disk, 102% with Al/Cu shielding disk, 95% with PMMA/Cu/PMMA shielding disk. The PDDs values of the gafchromic films in front of the disks were: 107%, 105%, 104%, and 94% for the Al/Pb, Al/Steel, Al/Cu, and PMMA/Cu/PMMA disks respectively. CONCLUSIONS: The dose values above and under the shielding disks were acceptable for the four studied shielding types. Demonstrated it is possible to use any of them clinically, while the best shielding disk was the Al/Pb since it has minimum thickness and a small backscatter enhancement.

[Not Available]. / Utilisation de la radiothérapie intra-opératoire dans le traitement conservateur d'un cas de cancer du sein invasif chez un home.

Male breast cancer is a rare disease, accounting for less than 1% of all breast cancer cases. It is often diagnosed late, at a more advanced stage than its female counterpart. Therefore, it is more commonly treated with mastectomy. In early stages, a conservative treatment associating lumpectomy, sentinel lymph node (SLN) biopsy and whole-breast external beam radiotherapy (EBRT) is possible and has been described. Recently, intra-operative radiation therapy (IORT) has been assessed as an alternative to EBRT in selected female breast cancer cases. Its use has never been described in male patients. In this article, we present the case of a 56 years old man treated with lumpectomy with the excision of the nipple-areola complex, SLN biopsy, and IORT with electron beams (IOERT), for early breast cancer disease. This case demonstrates that the IORT technique is feasible on men with early breast cancer (pT1N0).

Early invasive cancer and partial intraoperative electron radiation therapy of the breast: experience of the jules bordet institute.

Objectives. The aim of this prospective phase II study is to evaluate the treatment of early-stage breast cancer (T1 N0) with intraoperative electron radiation therapy (IOERT) in terms of local control, early complications, and cosmesis. Patients and Methods. From February 2010 to February 2012, 200 patients underwent partial IOERT of the breast. Inclusion criteria were unifocal invasive ductal carcinoma, age ≥40 years, histological tumour size ≤20 mm, and no lymph node involvement. A 21 Gy dose was prescribed over the 90% isodose line in the tumour bed. Median follow-up is 23.3 months (7-37). Results. Acute toxicity was not frequent (Grade 1: 4.5%, Grade 2: 1%). The cosmetic result was considered to be very good or good in 92.5%. One ipsi lateral out-quadrant recurrence at 18 months was observed. The crude and actuarial local recurrence rates after median follow-up were 0.5% and 0.9%, respectively. Conclusion. The preoperative diagnostic work-up must be comprehensive and the selection process must be rigorous for this therapeutic approach reserved for small ductal unifocal cancers. After a 23.3-month median follow-up time, the clinical results of IOERT for selected patients are encouraging for the locoregional recurrence and the toxicity rates. The satisfaction of our patients in terms of quality of life was extremely high.

Correlation of Hsp110 expression with caspase-3 and -9 during apoptosis induced by in vivo embryonic exposition to retinoic acid or irradiation in early mouse craniofacial development.

OBJECTIVE: To analyze the expression and role of three proteins (HSP110, caspase-3 and caspase-9) during craniofacial development. DESIGN: Seven pregnant C57Bl/6J mice received, by force-feeding at gestation day 9 (E9), 80 mg/kg of all-trans retinoic acid mixed to sesame oil. Seven pregnant NMRI mice received two grays irradiation at the same gestation day. Control mice of both strains (seven mice for each strain) were not submitted to any treatment. Embryos were obtained at various stages after exposition (3, 6, 12 and 24 h), fixed, dehydrated and embedded. Coronal sections (5 microm) were made. Slide staining occurred alternatively using anti-Hsp110, anti-caspase-3 and anti-caspase-9 immunohistochemistry. RESULTS: Expression of HSP110, caspase-3 and caspase-9 was found in cells of well-known locations of programmed cell death. After retinoic acid exposure, expressions were increased especially in neural crest cells of mandibular and hyoid arches. Quantification of positive cells shows that caspase-9 and Hsp110 were expressed before caspase-3. After irradiation, the expression of the three proteins quickly increased with a maximum 3 h after irradiation. For all three models of apoptosis (physiological, retinoic-induced and irradiation-induced) HSP110 positive cells were more numerous than caspase-3 positive cells. Caspase-3 positive cells were more numerous than caspase-9 positive cells especially in mesectodermal irradiation-induced apoptotic cells. CONCLUSION: The findings show a potential function of HSP110 in apoptosis during embryo development. Caspase-3-expressing cells are more numerous than cells expressing caspase-9, especially irradiation-induced apoptotic neural crest cells. This suggests that other caspases, still to be identified, may activate caspase-3 in this model.

[Neoadjuvant radiochemotherapy and surgery of locally advanced cervical carcinoma: review of 22 patients treated at the Bordet Institute]. / Traitement par radio-chimiothérapie néoadjuvante et chirurgie du cancer du col utérin localement avancé: revue de 22 patientes à l'Institut Bordet.

OBJECTIVES: Concomitant chemoradiation is the "new gold standard" for dealing with locally advanced cervical carcinoma, but what about surgery? We don't know yet to what extent surgery is necessary and how radical it must be when it is performed. In this study, we present the analysis of the results obtained in patients treated by concomitant chemoradiation followed by radical surgery. MATERIALS AND METHODS: Twenty-two patients, median age 49 years, with I(b) - III(a) cervical tumors were enrolled to be treated by concomitant chemoradiation followed by radical surgery. The chemoradiation protocol included external radiotherapy to the pelvis: 45 Gy; Cisplatin 40 mg/m(2) in continuous intravenous infusion once a week (5 weeks) followed by brachytherapy one week later. Surgery was performed 4 to 6 weeks later and consisted in radical hysterectomy with pelvic lymphadenectomy. RESULTS: 20/22 patients underwent surgery after chemoradiation because of a diagnosis of lung metastases in one and presence of a nonresectable metastasis for the other. A complete pathological response was demonstrated in 12/20 patients (60%), a microscopic residual tumor in 7 patients (35%), and residual disease <1cm in 1 patient (5%). CONCLUSION: This study showed a particularly high rate of pathologic responses (T(0)+T(mic): 95%) and of local control. We don't know yet if surgery is a real necessity or if it could be less extended after concomitant chemoradiation.

[Expression of caspase 3 and p53 during physiological apoptosis and apoptosis induced by three teratologic agents during early craniofacial development of the mouse embryo]. / L'expression de la caspase 3 et la protéine p53 au cours de l'apoptose physiologique et induite par 3 agents tératogènes au cours du developpement crânimofacial précoce de l'embryon de souris.

The neural crest-derived mesectoderm gives rise to physiologic apoptosis areas in early vertebrate embryos. Certain teratologic agents increase this phenomenon. The purpose of this work was to detect caspase 3 (which is associated with the apoptosis cascade) and p53 in cell death areas, both during physiological apoptosis and during apoptosis induced by three agents (retinoic acid, methyl-triazene, irradiation). Antibody revelation was performed using the aBC peroxidase kit. Quantifications were also performed on histological sections. We observed caspase 3 uptake on some apoptotic and preapoptotic cells in control embryos, and in the embryos exposed to the three teratogens. Immunoreactivity generally preceded the development of cytological features of apoptosis. However, p53 was expressed only in the embryos exposed to ionizing radiation and methyl-triazene (an alkylating agent), but not significantly in embryos exposed to retinoic acid. The present results throw some light on apoptosis mechanisms in several teratologic conditions.

[Why radiation for the postmastectomy patient?]. / Pourquoi irradier une patiente mastectomisée?

We can identify a subgroup of patients with a high risk of loco-regional relapse after mastectomy. When those patients are irradiated, their absolute loco-regional relapse risk drops for more than 10% with a relative risk reduction of 66% (p < 0.0001). The severe complication rate is below 1%. With earlier radiotherapy techniques, there was an excess in long term cardiac mortality among irradiated patients. Even if the breast specific survival was improved with radiotherapy, the overall survival was not better. Three recent randomised trials have shown that postmastectomy radiotherapy adds 10% survival benefit to an adjuvant systemic treatment. The impact of radiotherapy on overall survival is more pronounced for less advanced tumors.

Effects of irradiation and methyl-triazene on craniofacial development in mouse embryos: a semiautomated morphometric analysis.

OBJECTIVE: The purpose of the present study was a 2D-semiautomated morphometric analysis of craniofacial growth in nuclear magnetic resonance imaged (NMRI) mouse embryos. METHODS: The NMRI mouse embryos were exposed in utero to either a single dose of 2 Gy X-irradiation on day 9 of gestation (113 embryos) or to 1.5 mg methyl-triazene administered orally to their pregnant mothers on gestational day 10.5 (124 embryos). An additional group of 108 embryos was used as controls. Digitized pictures of embryos from gestational days 14 to 17 were taken in lateral right view using a video system. Landmarks were located and digitized for computerized analysis of growth changes in relation to developmental stages of the face. RESULTS: The results revealed that the snout of control embryos lengthens during the developmental period considered. The snout of embryos previously submitted to methyl-triazene displayed micrognathia, and all treated fetuses exhibited macroscopic signs of microcephaly with a reduced mandible. The snouts of irradiated embryos appeared shortened at the 14-day stage and continued to shorten as development proceeded. A shortening of the midface was detected macroscopically in 83% of the cases. CONCLUSION: The results of this morphometric analysis enabled us to trace the developmental progression of the induced dysmorphosis and to assess the differences compared with normal development.

Effects of irradiation on facial development in mouse embryos.

The purpose of this study was to observe the effects of irradiation on the craniofacial development of NMRI mouse embryos. Two populations of pregnant mice were irradiated with a single dose of 2 Gray on day 8 of gestation for the first population (Po. 1) and on day 9 of gestation for the second population (Po. 2). On gestational days 9 to 17, embryos were submitted to histological and scanning electron microscope examinations. The two populations of embryos presented a high percentage of centro-facial hypoplasia (74.7% for Po. 1 and 75% for Po. 2) which was more pronounced in the latter one. Ocular anomalies were present in 16% of the first population. Cases of anencephaly, cleft palate and anomalies of the central nervous system were found in both populations.

[What is the role of radiotherapy in the treatment of breast cancer in 1995?]. / Quel est le rôle de la radiothérapie dans le traitement du cancer du sein en 1995?

In 1995, radiotherapy continues to remain one important component in the treatment of breast cancer both for the breast conserving approach and after a mastectomy in case of more locally advanced disease: it helps to improve the local control and so to safe more breast or to avoid a relapse in the mastectomy scar, a source of distress for the woman. Nevertheless, this modality requires a precise technique and integration with surgery and chemotherapy. Besides this curative approach, radiotherapy plays an important role in the treatment of brain or bone metastases where it is quite useful to improve the patient's quality of life.

The place for surgery in central recurrences of invasive cancer of cervix uteri.

Between 1988 and 1991, at the Jules Bordet Institute in Brussels, 11 patients were submitted to a surgical treatment due to an uterus cervix central recurrence. The majority were of the epidermoid type. The primary stage of the lesion at the moment of diagnosis varied from stage Ib to stage IIIb lesions. Six of the eleven patients were not submitted to an adequate initial treatment. These recurrences appeared between the 4th and the 264th month after the initial treatment. The treatments, which were determined according to the site of recurrence, consisted of: an anterior pelvic exenteration for four patients, a total exenteration for one patient, for two of them a total hysterectomy with bilateral salpingo-oophorectomy and partial cystectomy, a cervix amputation for another one and finally, for the last three ones, a laparotomy with debulking or derivation colostomy. The mortality during and after the operation was nil but there were several short term complications. After a minimal 19 months follow-up we could see that three patients survived, one was generalized and seven died. Due to the scarce number of patients and pathological disparity of them, the authors reviewed the literature concerning this problem, in order to determine some guidelines for similar cases. In spite of its consequences, surgery seems to be the only valid solution to propose to these patients, not only to give them a chance to survive but also to improve their life quality.

The phosphatidylcholine metabolism in the renal tissue during experimental acute and chronic pyelonephritis in the rabbit.

In 139 adult male rabbits unilateral pyelonephritis (PN) was induced. In a broad spectrum of enzymes and phospholipids also the content of phosphatidylcholine (PC) was determined. Only these latter values are reported here. PC showed markedly increased levels up to the 20-d-, and to the 31-d-series in the cortex. After 64 and 100 d of experimental PN the content of PC was less than the half of the normal values, and after 261 d of disease, it was only about 1/16 of the normal value (= 22.58 +/- 1.55 micrograms P/g wet weight). In the medulla the PC increased only till the 20-d-series, but showed a marked decrease in the 31-d-series already, which is in contrast to the corresponding cortical situation. Thereafter the medullary PC decreased successively, so that only about 5 per cent of the normal value were found in the contracted kidneys of the 261-d-series (n = 13.58 +/- 1.24 microgramsP/g wet weight). The increased PC-concentrations should be due mainly to the increased cell contents, the following reductions being due to the lower cell contents of this interstitium. Other factors (induced synthesis and/or reduced decomposition) may be responsible to a lesser degree of probability. The strongly decreased PC concentrations in the chronic and late-chronic series are caused by the low cell-contents, increasing vascular changes, the augmented connective tissue, and the general epithelial damage of the remaining nephrons.

Renal fumarase-activities during experimental and chronic human pyelonephritis.

In chronic experimental and human pyelonephritis (PN) renal enzyme and phosphatide analyses as well as quantitative histological examinations were performed simultaneously. The results reported in this study only refer to fumarase (FUM) activities. Glomerular FUM-activities initially increased steeply up to 31 days, thereafter the values decreased, but being still elevated till 212 days. Only in the 261-days series the FUM-activities were absolutely decreased. In the cortical tubules of the rabbit kidneys the enzyme activities also steeply increased until 64 days, in the 100-days-series they were already depressed. After 212 and 261 days the tubular FUM-activities were extremely depressed. In the medulla the FUM-activities similarly showed steeply increasing values till 31 days. Thereafter a decrease was stated in the 64-days-series persisting up to 100 days. Finally, the values were pathologically depressed in the 212- and 261-days-series. In the "spontaneously healed up" tissue the glomerular FUM was slightly increased, the cortico-tubular one was more increased whereas the medullar activities were decreased. The human samples of pyelonephritic nephrocirrhosis showed about half than the normal FUM-activities in the glomerula. In the cortical tubules they were still more depressed. Also in the medulla the values were decreased. The significance calculations (universally applied t-test) showed an overwhelming majority of values with significance (p less than 0.001). The measured enzyme activities well correlate with the results of quantitative histological examinations.

Citrate-synthase activities in the renal tissue during experimental and chronic human pyelonephritis.

In chronic experimental and human pyelonephritis (PN) renal enzyme and phosphatide analyses and quantitative histological examinations were performed. The results reported in this study only refer to citrate-synthase activities (= condensing enzyme = CE). 139 rabbits developed unilateral experimental pyelonephritis, in further 19 rabbits the experimental PN did not settle or "healed up spontaneously". 31 samples of human pyelonephritic nephrocirrhotic kidneys and 20 samples of healthy human kidneys were examined in the same manner. The glomerular CE-activities in the rabbit increased steeply in the 20- and 31-days-series, remained at a high level up to the 100-days-series, showed normal values in the 213-days-series, and permitted a marked decrease to be seen in the 261-days-series only. The corticotubular CE-activities increased steeply in the 20- and 31-day-series, still being above the normal values in the 64-days-series. Thereafter, only reduced and strongly reduced values were observed. In the pyelonephritic medulla of rabbits the CE-activities increased very steeply during the 20-days-series, were still above the level of the normal values up to the 100-days-series, dropping then to pathologically reduced data in the 212-days-series. Thus the CE-activities showed a similar type of behaviour to that of the corresponding glomeruli. Chronically pyelonephritic contracted renal tissue in human beings also showed major reductions in CE-activities in all three tissue fractions studies. The significance calculations (universally applied t-test) showed an overwhelming majority of significant values (p less than 0.001).

[The maximum adsorptive capacities of three activated carbons produced in the GDR for barbiturates, other hypnotics and tranquilizers from aqueous and low-percentage ethanolic solutions (author's transl)]. / Maximale Adsorptionskapazitäten aus wässrigen und niederprozentig-ethanolischen Lösungen für Barbiturate, andere Hypnotica und Tranquilizer an 3 DDR-Aktivkohlen.

A standardized stirred-batch experiment has been performed to determine the maximum adsorptive capacities of three activated carbons (R4, ASO and walnut coal) produced in the GDR for acetylsalicylic acid, methylsalicylate, phenobarbital, crotylbarbital, hexobarbital, pentobarbital, glutethimide, chlorophenethazine and methaqualone from aqueous and low-percentage ethanolic solutions. The activated carbon ASO and the walnut coal have always been found to be markedly superior to the activeated coal R 4. The maximum adsorptive capacities so far determined compare with data on activated carbons produced abroad, so that further developmental work seems worthwhile.20

Alanine-aminotransferase activities in the renal tissue during experimental and chronic human pyelonephritis.

In chronic experimental and human pyelonephritis (PN) simultaneously renal enzyme and phosphatide analyses and quantitative histological examinations were performed. The results reported in this study refer only to alanine-aminotransferase (AlAT) activities. 139 rabbits developed unilateral experimental pyelonephritis, in further 19 rabbits the experimental PN did not settle or "healed up spontaneously". 31 samples of human pyelonephritis nephrocirrhotic kidneys and 20 samples of healthy human kidneys were examined. Glomerular AlAT-activities increased initially up to the 31-days series, thereafter they decreased without any exception. In the cortical tubules of the rabbit kidneys the enzyme activities increased also up to the 31-days-series, later on they decreased extremely. The medullary AlAT-activities similarly showed increasing values till the 31-days-series, which were followed by sharply depressed data. In the "spontaneously healed up" tissue the glomerular AlAT was increased more than 100%, the cortico-tubular one nearly 100%, and the AlAT of the medulla paralleled the increased values of the 20-days series nearly. The human samples of pyelonephritic nephrocirrhosis showed in all 3 fractions (glomerula, cortical tubules and medulla) extremely depressed AlAT-activities. The significance calculations (universally applied t-test) showed an overhelming majority of the values with significance (p less than 0.001). The measured enzyme activities correlate well with the quantitative histological examinations.

[Value of antibiotic combination therapy in chronic pyelonephritis--study on a large number of patients over a period of 15 years]. / Der Vert der Antibiotikakombinationstherapie der chronischen Pyelonephritis--Untersuchungen an einem grösseren Krankengut in einem Zeitraum von 15 Jahren.

1. 448 patients with chronic pyelonephritis were treated over periods ranging from a minimum of 5 to a maximum of 15 years with our special form of intermittent long-term therapy with chemoprophylaxis in the intervals, the antibiotics - mostly in the form of combinations - and chemotherapeutics in the treatment-phases were always used only on the base of several antibiograms. During the last 11 years synergistic bactericidic combinations of antibiotics were used to an increasing degree. 2. A comparison of the efficacy of our form of therapy used now (since 1965/1966) with the results already published: 1966 (therapy span 1960-1965), 1970 (therapy span 1960-1969), and 1972 (therapy span 1960-1971) showed the following quotes of a transmission into a standstill (questionable healing) of the disease: 1966 (without periodic change of the urinary pH) 36,1% 1966 (with periodic change of the urinary pH) 69,4% 1970 (synergistic combinations of antibiotics) 68,3% 1972 (synergistic combinations of antibiotics) 78,7% 1976 (synergistic combinations of antibiotics) 82,1%. 3. On the basis of our results we consider the combinations of synergistic bactericidic antibiotics as a real enrichment of the therapy of chronic pyelonephritis.