Electron Phase Shift at the Zero-Bias Anomaly of Quantum Point Contacts.

The Kondo effect is the many-body screening of a local spin by a cloud of electrons at very low temperature. It has been proposed as an explanation of the zero-bias anomaly in quantum point contacts where interactions drive a spontaneous charge localization. However, the Kondo origin of this anomaly remains under debate, and additional experimental evidence is necessary. Here we report on the first phase-sensitive measurement of the zero-bias anomaly in quantum point contacts using a scanning gate microscope to create an electronic interferometer. We observe an abrupt shift of the interference fringes by half a period in the bias range of the zero-bias anomaly, a behavior which cannot be reproduced by single-particle models. We instead relate it to the phase shift experienced by electrons scattering off a Kondo system. Our experiment therefore provides new evidence of this many-body effect in quantum point contacts.

A single hole spin with enhanced coherence in natural silicon.

Semiconductor spin qubits based on spin-orbit states are responsive to electric field excitations, allowing for practical, fast and potentially scalable qubit control. Spin electric susceptibility, however, renders these qubits generally vulnerable to electrical noise, which limits their coherence time. Here we report on a spin-orbit qubit consisting of a single hole electrostatically confined in a natural silicon metal-oxide-semiconductor device. By varying the magnetic field orientation, we reveal the existence of operation sweet spots where the impact of charge noise is minimized while preserving an efficient electric-dipole spin control. We correspondingly observe an extension of the Hahn-echo coherence time up to 88 µs, exceeding by an order of magnitude existing values reported for hole spin qubits, and approaching the state-of-the-art for electron spin qubits with synthetic spin-orbit coupling in isotopically purified silicon. Our finding enhances the prospects of silicon-based hole spin qubits for scalable quantum information processing.

Upstream modes and antidots poison graphene quantum Hall effect.

The quantum Hall effect is the seminal example of topological protection, as charge carriers are transmitted through one-dimensional edge channels where backscattering is prohibited. Graphene has made its marks as an exceptional platform to reveal new facets of this remarkable property. However, in conventional Hall bar geometries, topological protection of graphene edge channels is found regrettably less robust than in high mobility semi-conductors. Here, we explore graphene quantum Hall regime at the local scale, using a scanning gate microscope. We reveal the detrimental influence of antidots along the graphene edges, mediating backscattering towards upstream edge channels, hence triggering topological breakdown. Combined with simulations, our experimental results provide further insights into graphene quantum Hall channels vulnerability. In turn, this may ease future developments towards precise manipulation of topologically protected edge channels hosted in various types of two-dimensional crystals.

Results of a prospective dose-intensive regimen in 27 patients with small cell carcinoma of the ovary of the hypercalcemic type.

BACKGROUND: The evaluation of first-line intensive combination therapy in small cell carcinoma of the ovary (SCCO). PATIENTS AND METHODS: Debulking surgery; four to six cycles of chemotherapy with cisplatin (P) 80 mg/m(2) day 1, adriamycin (A) 40 mg/m(2) day 1, vepeside (V) 75 mg/m(2)/day days 1-3, cyclophosphamide (EP) 300 mg/m(2)/day days 1-3, every 3 weeks and granulocyte colony-stimulating factor with, in case of a complete remission, high-dose chemotherapy with carboplatin, vepeside, cyclophosphamide and stem-cell support. RESULTS: Twenty-seven patients (median age 25 years); International Federation of Gynecology and Obstetrics stage: five I, four IIC, 17 IIIC-IV and one unknown. Twenty patients underwent complete surgery. Eight patients progressed under chemotherapy. Among 18 patients in complete response (CR), 10 received high-dose chemotherapy (CT) (three stem-cell collection failures, two protocol violations, two disease progression and one refusal). The main grade 3-4 toxic effects were hematologic. There were eight relapses among the 18 CR, four of which were pelvic alone. Among the 27 patients, 13 died and 10 patients are in CR1, three in CR2. The median follow-up is 37 months (8-166) and the median duration of the 18 CR is 30 months (5-111). Overall survival at 1 and 3 years is 58% [confidence interval (CI) 40% to 75%] and 49% (CI 30% to 67%). CONCLUSIONS: Initial dose-intensive therapy achieves interesting overall survival in SCCO.

Toxic encephalopathy and noise-induced hearing loss.

In several laboratory animal studies, it has been documented that the hearing, vision, and brain can be injured due to exposure to organic solvents. This finding formed the background for a pilot study (n=16) aimed at identifying new ways of qualifying diagnostics, treatment, and rehabilitation of patients suffering from brain injury due to exposure to organic solvents, also referred to as toxic encephalopathy. Diagnosing toxic encephalopathy is complicated because the symptoms of this type of diffuse brain injury are non-specific. So, it was initially hypothesised that some of the difficulties involved in diagnosing toxic encephalopathy could be minimized by extending the diagnostic procedure. Apart from clinical interviewing and neuropsychological testing, the diagnosis should include the examination of hearing and vision. This will help in achieving new measures that could improve in diagnosing toxic encephalopathy with more certainty. On the basis of ranking, only one patient in the pilot study was considered to have a normal neuropsychological test profile, which was defined as a test profile without any marked deviations when compared with a normal population. A total of 10 patients were considered to have "discrete problems." These patients had a test profile showing either a few strikingly negative results or an array of results slightly below the expected level when compared with a normal population. A total of four patients were considered to suffer from "moderate problems" and one patient from "severe problems." The patients with "moderate problems" and "severe problems" showed consistent negative results and an unambiguous negative test profile. However, the overall results of all neuropsychological examinations performed revealed a dispersed picture. Quite remarkably, all the 13 patients who had their hearing examined showed a loss of hearing, 7 patients complained about tinnitus, and all patients had a history of exposure to both noise and organic solvents, which had not been observed at the initial examination, but seemed to have serious implications for their prognosis and future life.

Transport of Na+ by monensin across bimolecular lipid membranes.

Transmembrane 22Na fluxes across bimolecular lipid membranes are measured under two different experimental conditions: (a) the pH is the same in the two bulk aqueous solutions on either side of the membrane while the concentrations of Na+ are different; (b) the concentration of Na+ are identical but pH of the two solutions are different. In this latter case, the transport of Na+ occurs in the opposite direction to the difference of the proton concentration. In both cases, the electrical charge flux in negligible. A transport model is proposed to account for the experimental data.

Inhibition of fasL sustains phagocytic cells and delays myogenesis in regenerating muscle fibers.

Macrophage-muscle cell interactions are complex, and the majority is unknown. The persistence of inflammatory cells in skeletal muscle could be critical for myofiber viability. In the present paper, we show that FasL plays a role in the resolution of muscle inflammation. We analyzed inflamed muscles of normal mice treated from day 3 to day 8 with a FasL inhibitor (Fas-Ig) or with control Ig. Treated muscles were collected at 3, 5, and 10 days. The treatment with recombinant Fas-Ig protein induced a severe persistence of inflammatory cells at 5 days (115,000+/-27,838 vs. 41,661+/-6848, p<0.01) and 10 days from injury (145,500+/-40,850 vs. 5000+/-1000, p<0.001). Myofiber regeneration was highly impaired (37+/-14 vs. 252+/-28, p<0.01). Apoptosis of phagocytic cells was absent during Fas-Ig treatment (0.9+/-0.6 vs. 1300+/-150, p<0.0001), but apoptotic, mononucleated cells appeared at day 10, 2 days after the suspension of Fas-Ig administration. The time course of FasL expression during muscle inflammation, at mRNA and protein level, reveals a peak during myoblast proliferation. The peak of FasL expression coincides with the peak of apoptosis of phagocytic cells. In situ hybridization shows the co-expression of FasL and MyoD mRNA in mononucleated cells, i.e., myoblasts. Experiments on the myoblast cell culture confirmed the expression of FasL in myoblasts. The findings shown here indicate one of the pathways to control myoblast-macrophage interaction and might be relevant for the control of inflammatory cells in muscle tissue. Perhaps altering FasL expression with recombinant proteins could ameliorate inflammation in degenerative myopathies and up-regulate muscle regeneration.

Erdheim-Chester disease. Clinical and radiologic characteristics of 59 cases.

We made a retrospective evaluation of clinical and radiologic features, treatment, and outcome of Erdheim-Chester disease, a rare non-Langerhans cell histiocytosis. We had 7 patients coming from 3 French teaching hospitals and reviewed 52 cases from the literature. These cases were considered to have Erdheim-Chester disease when they had either typical bone radiographs (symmetrical long bones osteosclerosis) and/or histologic criteria disclosing histiocytic infiltration without features for Langerhans cell histiocytosis (no S-100 protein, no intracytoplasmic Birbeck granules). Ages at diagnosis ranged from 7 to 84 years (mean +/- SD = 53 +/- 14 yr) with a male/female ratio of 33/26. Bone pain was the most frequent clinical sign (28/59), mostly located in the lower limbs. Exophthalmos and diabetes insipidus were found in respectively 16/59 and 17/59 patients. General symptoms (fever, weight loss) and "xanthomas" (mainly located on the eyelids) were present in 11/59 patients. Retroperitoneal involvement was found in 17/59 patients. Skeletal X-ray showed typical osteosclerosis of the diaphysis of the long bones in 45/59 patients. Bone radiographs showed osteolytic lesions of the flat bones (skull, ribs) in 8 patients. Histologic diagnosis was performed after a bone biopsy (28 patients), a retroorbital biopsy (9 patients), and/or a biopsy of the retroperitoneal infiltration or the kidney (11 patients). Six of our 7 patients but only 5 of 52 patients from the literature had the complete histologic criteria, disclosing no Birbeck granules or S-100 immunostaining. In other cases, histologic results usually described a xanthogranulomatous infiltration by foamy histiocytes nested in fibrosis. Treatment was corticotherapy (20/59), chemotherapy (8/59), radiotherapy (6/59), surgery (3/59) and immunotherapy (1 patient). Twenty-two patients died after a mean follow-up of 32 +/- 30 mo (range, 3-120 mo). In conclusion, Erdheim-Chester disease may be confused with Langerhans cell histiocytosis as it sometimes shares the same clinical (exophthalmos, diabetes insipidus) or radiologic (osteolytic lesions) findings. However, it also appears to have distinctive features. Patients are older and have a worse prognosis than those with Langerhans cell histiocytosis, and the diagnosis relies on the association of specific radiologic and histologic findings.

Management of breast cancer in the elderly.

The management of breast cancer in elderly women was analysed by a retrospective study of 150 women over 70 years old referred to our department between 1984 and 1988. 80 were T1-T2, 33 were T3 and 34 were T4. 107 were N0 and 43 were N1-N2. 16 women (11%) were in poor health, preventing conventional treatment. Treatment choice varied with age: 60% of the women aged 70-79 (group 1) and 23% of the oldest women (group 2) were treated conventionally. The use of surgery decreased with age and surgical procedures were conventional in only 85% of the group 1 women and in 56% of the group 2 women. Definitive radiation therapy was used more frequently in the oldest women, as was primary hormone therapy. Quality of follow-up also varied with age. Five-year survival rates were still high in both groups while relapses were frequent. Breast cancer was consequently a frequent cause of death. The increase in the proportion of elderly people with breast cancers over the next few years will require validated guidelines. Specific protocols and specific rules of management must be drawn up.

External irradiation prior to conservative surgery for breast cancer treatment.

From 1981 to 1987, 138 patients with breast cancer unsuitable for primary tumorectomy received initial external radiotherapy (45 Gy/25f/35d) in order to reduce the tumor volume so that secondary limited surgery could be performed. There were 81 T2 and 57 T3. Fifty-seven percent of the patients had a tumor larger than 4.5 cm. After completion of the radiotherapy, 22 patients (16%) showed no more evidence of a tumor either clinically or radiologically and received a boost of 25 Gy. In 52 cases (38%) the tumor regression allowed for secondary tumorectomy followed by a boost of 20 Gy. Sixty-four patients (46%) showed either little or no tumor regression: radical surgery was performed in 14 cases (10%) and high dose boost curietherapy (37 Gy) in the 50 (36%) remaining patients who refused mastectomy. Breast conservation in good condition was thus obtained in 74 patients (54%). Sufficient tumor regression to allow secondary tumorectomy was more often observed in T2 than in T3, in poorly differentiated tumors or mucinous type, and in tumor with well defined mammographic aspects. Actuarial 5-year local control and disease-free survival rates after limited surgery were, respectively, 90% and 73%. No particular complications were observed after secondary tumorectomy. This therapeutic approach is encouraging in patients with large T2 and T3 breast tumors, but a longer follow-up is required to assess definitive conclusions.

Pure acute monocytic leukemia. A study of 12 cases.

Twelve cases of pure acute monocytic leukemia in adults were studied. They were selected on the basis of the morphology of the blast cells on Romanowsky-stained smears of blood and bone marrow, as well as positivity of the cells for the naphthol ASD acetate esterase reaction specifically inhibited by sodium fluoride. There was no sex predominance. Neoplastic involvement of the skin and/or gingiva was very frequent. The leukemic proliferation in blood and bone marrow consisted of monoblasts, promonocytes and monocytes. The peroxidase reaction was negative or only faintly positive. Serum and urinary lysozyme levels were increased. The blast cells retained their ability to stimulate, in vitro, colony formation by normal bone marrow cells used as targets. All of these characteristics permit specific identification of this type of acute leukemia. The prognosis is grim: only five of 12 patients achieved complete remission, and four of these five had relapses in less than 14 months; the median survival was five months.

The lack of efficacy of 4,6,6'-trimethylangelicin to induce immune suppression in an animal model for photopheresis: a comparison with 8-MOP.

Photopheresis is an extracorporeal form of photochemotherapy with 8-methoxypsoralen (8-MOP) and UVA (PUVA). Patients ingest 8-MOP and then a psoralen-rich buffy coat is obtained by centrifugation and mixed with saline. This mixture is recirculated through a UVA radiation field and then reinfused. Photopheresis appears to be effective for several T cell-mediated disorders, because the treatment results in a specific immune response against the pathogenic clone of T cells involved. With PUVA therapy, the whole body of the patient is exposed to UVA, after ingestion of 8-MOP. Upon UVA exposure 8-MOP binds to, amongst others, DNA and induces DNA monoadducts and interstrand cross-links. As a result of these photoadducts photocarcinogenicity is a risk in PUVA. In PUVA for psoriasis, it proved that angular furocoumarins, although almost incapable of inducing DNA cross-links (less carcinogenic), are still effective. In order to determine if monoadducts induced by photopheresis could also be effective we used, specifically, 4,6,4'-trimethylangelicin (TMA). In this report, we compare the photodegradation of both TMA and 8-MOP under conditions relevant to the in vivo situation, as well as the effect both compounds have on the viability of rat lymphocytes as measured with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. We show that TMA did not induce immunosuppression in vivo, even after extensive irradiation. In addition a dose dependency of 8-MOP/UVA versus the induced immune suppression was carried out. It was shown that there is a log dose/response correlation of r=0.9205.

Evaluation of the regional cerebral vasodilatory capacity before carotid endarterectomy by the acetazolamide test.

To estimate the regional perfusion pressure and possibly the stump pressure during carotid endarterectomy, cerebral blood flow (CBF) measurements including a vasodilatory test were performed preoperatively. CBF was measured by 133Xe inhalation and emission tomography. An intravenous dose of 1g acetazolamide (Diamox) was used as cerebral vasodilator. Thirty-six patients with a clinical history of previous strokes (9 cases) or transient ischaemic attacks (27 cases) were studied. Nine of the patients showed occlusion of the contralateral internal carotid artery (ICA). The percent flow increase induced by Diamox in the ipsilateral hemisphere correlated to the ICA pressure was measured before clamping (n = 32, r = 0.55, p less than 0.001). In 12 of the 36 patients, Diamox caused a significant change in the flow distribution indicating a restricted regional vasodilatory capacity and a reduced regional perfusion pressure. In addition, these 12 patients showed a low stump pressure (less than 50 mmHg). However, 8 additional patients had uniform CBF increases at the Diamox test, but showed low stump pressures. It is concluded, that preoperative tests of the cerebral vasodilational capacity can be used to identify most patients with a low ICA pressure, and a substantial fraction of patients that will develop a low stump pressure upon ICA clamping during operation. In these patients with abnormal Diamox tests surgical reconstruction is particularly indicated, but, at the same time the perioperative risks are presumably highest in this group.

Interobserver variation in the detection of pulmonary venous hypertension in chest radiographs.

A total of 171 sets of chest radiographs chosen randomly were reviewed independently by two residents in their second year of training, and two experienced radiologists. The degree of interobserver agreement in an overall assessment of pulmonary venous hypertension and in the assessment of five signs, indicative of pulmonary venous hypertension was determined by kappa statistics. The average level of agreement was moderate (0.51-0.56) for the overall assessment and the signs of perivascular clouding, perihilar haze and pleural effusion, and poorer (0.31-0.38) for flow shift and Kerley lines. In the overall assessment agreement between experienced radiologists was slightly better (0.63) than average. Multiple reader interpretation is recommended for the assessment of low-grade pulmonary venous hypertension.

Prognostic factors in patients with localized Ewing's sarcoma: the effect on survival of actual received drug dose intensity and of histologic response to induction therapy.

To bring to the fore the most important prognostic factors in Ewing's sarcoma (ES) with current protocols, we studied the classical prognostic factors, dose intensity (DI) of actual received drugs, age and histological response to induction therapy and their correlation in 39 patients with localized ES treated from 11/85 to 06/95 to identify eventual predictors of event-free survival (EFS). Inclusion criteria were age 35 yr or less, definitive local treatment by our team and chemotherapy including at least 4 drugs: vincristine (VCR), dactinomycin (DACT), doxorubicin (DOXO) cyclophosphamide (CPX). The endpoint was the absence of relapse. Parameters related to the status of patients were tested using the Chi square test or Fisher's exact test. The non parametric Kruskal-Wallis test was used for quantitative data. When necessary stratified analysis was done using the Mantel Cox test. With a median follow-up of 7 yr, overall survival (OS) and EFS were both 67% at 7 yr. According to univariate analysis, the significant predictors of survival were the DI of VCR and DACT, the histological response to preoperative chemotherapy (CT), the patient's age (< 18 yr DFS: 84%; > 18 yr DFS: 38%). The risk of metastases was almost tenfold higher in patients with low received DI of VCR (DFS 40% versus 95%) and of DACT (DFS 48% versus 94%). The prognostic value of primary tumor characteristics (tumoral volume or location) was erased by the comprehensive treatment. Following multivariate analysis, the actual received DI of VCR (p < 0.02) and DACT (p < 0.03) and the histological response to preoperative CT (p < 0.05) were retained as the only significant independent predictors of EFS. Taking into account the actual received DI of VCR and DACT, the prognostic value of age disappears. In conclusion, this study points out the main role of the drug DI in ES (particularly VCR and DACT) and of histological response to preoperative CT.

Cancer: the role of extracellular disease.

Invasive carcinoma originates from the epithelial cells lining the lumen of an organ. It is often preceded by metaplasia, dysplasia or carcinoma in situ. The purpose of this review is to suggest that this disease of the epithelium may be, in part, the result of underlying tissue-based disorganization. Human cancer is frequently associated with pre-existing tissue disease. For example, hepatocellular carcinoma usually occurs in patients with a macronodular cirrhotic liver. Most lung cancers arise among patients with chronic lung disease (bronchitis, emphysema, and chronic infection). Mechanical forces appear to play a major role in regulating normal and cancer cell growth. The loss of cell polarity by neoplastic cells, coupled to an otherwise normal growth rate is enough to explain the cancer star-shaped pattern. By changing the plane of cell division, tumor cells may escape physical constraints from surrounding cells and divide. Loss of cell polarity and the resulting cell proliferation appears to be a consequence of either tissue-based disorganization (chronic inflammation, fibrosis) or of direct carcinogenic insult. The multiple mutations frequently described in cancer may be, in part, secondary to physical stress and not primary events. Several animal and clinical trials have shown that tissue disruption (i.e. radiation-induced fibrosis or liver cirrhosis) can be successfully treated. It is possible that treatment targeted at tissue disruption would delay or reduce cancer incidence regardless of the precise biological mechanism of carcinogenesis.

[Chemotherapy of metastatic breast cancer]. / Chimiothérapie du cancer du sein métastatique.

The most powerful prognostic factor in the treatment of metastatic breast cancer continues to be the response to induction chemotherapy. The range of drugs which are widely used in the treatment of advanced disease, the anthracyclines, the taxanes and vinorelbine, have all shown interesting activity in terms of their ability to obtain both high response rates and long duration of response. The anthracyclines, doxorubicin (DX) and epiadriamycin (EPI) constitute the established reference agents in the treatment of metastatic disease, and combinations of these drugs with vinorelbine (VRB) and the taxanes, paclitaxel (PTX) and docetaxel (DCT), have produced major increases in objective response rates: PTX-DX (58%), DCT-EPI (69.4%), PTX-EPI (71.1%), VRB-DX (75%), VRB-EPI (77.1%). Suggestions for other combinations of chemotherapeutic agents which do not include anthracyclines available with well tolerated and effective drugs. The way forward after a response has been obtained remains an open question in which the limited efficacy of the available drugs and their cumulative toxicity needs to be balanced against the quality of life of patients during their disease. Defining the optimal strategy for the management of disease after induction treatment is a problem which needs to draw on the results of research, analysis of experience and insight into the needs of patients.

[Efficacy and toxicity of intrapleural mitoxantrone: apropos of 18 cases of pleural metastases of breast cancer]. / Efficacité et toxicité de la mitoxantrone par voie intrapleurale: à propos de 18 cas da métastases pleurales de cancer du sein.

Mitoxantrone, an anthracenedione, has been shown to be as effective as doxorubicin, but with less local or systemic toxicity, when used for the treatment of advanced breast cancer. As the high molecular weight and hydrophilic property of this drug let us predict a slow intracavity resorption, we tested its use in the treatment of malignant effusions refractory to systemic chemotherapy. 18 women, 43 to 83 years old, with cytologically demonstrated metastatic pleural effusions, and with prominent clinical symptoms, were included in the study. All these patients were refractory to hormonotherapy and combination chemotherapy (previous regimens included anthracyclines in 17 patients but none had received systemic mitoxantrone). No previous local treatment had been attempted. During the study period, no other treatment has been given. Mitoxantrone (6 mg/m2) has been administrated after effusion aspiration. A complete response was seen in 8 patients, a partial response in 5, and no change in the 5 others but one had received only one injection on account of a transitory shock immediately after. No others side effects were reported (fever, local pain, alopecia, vomiting). No patient had evidence of myelosuppression. These results suggest that intracavity injection of mitoxantrone is feasible and generally safe in most patients. Some efficiency has been seen in previously heavily treated patients refractory to systemic chemotherapy. Local administration of mitoxantrone deserves further investigation.

[Acute leukemia and breast cancer : apropos of 12 cases observed in the Department of Oncology at the Henri Mondor Hospital]. / Leucémie aiguë et cancer du sein : à propose de 12 cas observés dans le département de cancérologie de l'Hôpital Henri Mondor.

The authors report 12 cases of acute leukemia observed after breast cancer. 4 patients received only adjuvant radiotherapy, whereas the other eight received both chemotherapy and radiotherapy. Acute leukemia appeared with a mean time of 5.5 years after the detection of breast cancer and was preceded in 7 cases by isolated pancytopenia during 4 months. Acute leukemias were always non lymphoblastic and myelofibrosis was very frequent. A complete remission was obtained at three patients out of the seven treated. The mean survival time was 5.6 months. The existence of acute leukemia after chemo-and/or radiotherapy poses several problems. The detection of patients with a high risk of leukemia by different methods such as cytogenetic, studies of dysmyelopoietic symptoms, is actually often too late occurring during preleukemia states of bad prognosis. We also need to know the exact incidence of secondary leukemia after treatment of breast carcinoma and the real benefit of such treatment.

[Pre and postoperative chemotherapy of osteosarcoma with an adriamycin-cisplatin combination. Risks of a neoadjuvant chemotherapy which is not sufficiently effective]. / Chimiothérapie de l'ostéosarcome par l'association adriamycine-cisplatinum pré et postopératoire. Risques de la chimiothérapie néoadjuvante lorsqu'elle n'est pas suffisamment efficace.

The authors evaluated a new protocol of neoadjuvant chemotherapy for osteosarcoma, easier to manage and different from T10. The good results obtained with the postoperative ADR-CDDP association led us to undertake a pilot study between 1982 and 1984, using ADR-CDDP as preoperative chemotherapy. The records of sixteen patients were available for follow-up. The average age of the patients was 19.9 years. Patients received two or three preoperative courses, and a total of six identical courses. Tolerance was good. Pain usually disappeared but this was often misleading because associated with radiological and/or clinical tumor progression, low histological necrosis or poor outcome. The continuous disease-free survival actuarial rate was less than 57 and 40% at 18 months and two years respectively. The actuarial survival rate was 87% at one year and 65% at two years respectively. Disappointing results of this preoperative protocol, compared to results with the SO4 78 or T10 protocols for example, led to publish these data early in order to underline their potential dangers. As a result, we stopped our study. The charter of pilot studies justifies this publication. As well, these data point out the necessity of very close follow-up of neoadjuvant chemotherapy by sophisticated medical imaging. Neoadjuvant chemotherapy, if ineffective, must be stopped early, and should lead to surgery, followed by adequate postoperative chemotherapy.