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Background: The aim of this study was to evaluate the prognostic impact of quantitative estrogen receptor (ER) expression at relapse for ER-positive breast cancer with ER-positive recurrence., Patients and Methods: A total of 81 patients with ER-positive primary breast cancer and ER-positive paired recurrence were included. ER expression was evaluated as the percentage of tumor cells staining for ER under immunohistochemistry. Samples were defined as ER-high (ER>50%) or ER-low (ER≥10% and ≤50%)., Results: Quantitative ER expression on relapse biopsy was an independent prognostic factor for overall survival in multivariate analysis, both as a continuous (hazard ratio=0.8; 95% confidence interval=0.7-0.92, p=0.001) and as a categorical (ER-high vs. ER-low; hazard ratio=0.26; 95% confidence interval=0.11-0.59, p=0.001) variable. Patients whose status changed from ER-high (primary BC) to ER-low (relapse) had the poorest outcome, with a 10-year overall survival rate of 14%., Conclusion: Even in the case of maintenance of ER-positivity on primary and relapse of breast cancer, recurrence biopsy provides prognostic information., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Purpose: This is a randomized, double-blind, placebo-controlled study aimed to evaluate the clinical and biologic effects of letrozole plus lapatinib or placebo as neoadjuvant therapy in hormone receptor (HR) -positive/human epidermal growth factor receptor 2 (HER2) -negative operable breast cancer., Methods: Ninety-two postmenopausal women with stage II to IIIA primary breast cancer were randomly assigned to preoperative therapy consisting of 6 months of letrozole 2.5 mg orally daily plus lapatinib 1,500 mg orally daily or placebo. Surgery was performed within 2 weeks from the last study medication. Clinical response was assessed by ultrasonography. Pre- and post-treatment samples were evaluated for selected biomarkers. Fresh-frozen tissue samples were collected for genomic analyses., Results: Numerically similar clinical response rates (partial + complete response) were observed (70% for letrozole-lapatinib and 63% for letrozole-placebo). Toxicities were generally mild and manageable. A significant decrease in Ki-67 and pAKT expression from baseline to surgery was observed in both arms. Overall, 34 patients (37%) had a mutation in PIK3CA exon 9 or 20. In the letrozole-lapatinib arm, the probability of achieving a clinical response was significantly higher in the presence of PIK3CA mutation (objective response rate, 93% v 63% in PIK3CA wild type; P = .040)., Conclusion: The combination of letrozole-lapatinib in early breast cancer was feasible, with expected and manageable toxicities. In unselected estrogen receptor-positive/HER2-negative patients, letrozole-lapatinib and letrozole-placebo resulted in a similar overall clinical response rate and similar effect on Ki-67 and pAKT. Our secondary end point findings of a significant correlation between PIK3CA mutation and response to letrozole-lapatinib in HR-positive/HER2-negative early breast cancer must now be independently confirmed.

Background: Emerging literature data are showing that a change in human epidermal growth factor receptor (HER2) status adversely affects breast cancer patient's prognosis. The aim of this study was to evaluate the prognostic impact of HER2 loss in patients with HER2-positive disease treated with neoadjuvant therapy with or without anti-HER2 agents., Methods: One hundred and seven consecutive HER2-positive patients were identified from a prospectively maintained database. The first cohort includes 40 patients treated with chemotherapy (CT) alone. The second cohort includes 67 patients treated with neoadjuvant CT plus anti-HER2 agents (trastuzumab and/or lapatinib). HER2 expression was evaluated by immunihistochemistry or fluorescence in situ hybridization on pretreatment core biopsy and on surgical specimen after therapy., Results: The rates of pathologic complete response (pCR) and breast-conserving surgery were higher in the CT + anti-HER2 cohort. A loss of HER2 expression was observed in 40% of the patients with residual disease after CT alone versus 14.7% of the patients after CT + anti-HER2 agents (P = 0.019). Patients not achieving a pCR have a significant increase in the risk of relapse when compared with those achieving a pCR (hazard ratio [HR] 9.55, P = 0.028). Patients with HER2 loss tended to have a higher risk of relapse as comparing to patients with maintained HER2 positivity (HR 2.41, P = 0.063)., Conclusion: The pCR is confirmed as a powerful predictor of long-term outcome. The rate of HER2 loss is higher in patients receiving neoadjuvant CT without anti-HER2 agents. HER2 status on residual disease after preoperative therapy can be helpful in selecting patients at different risk of relapse, to be included in prospective trial exploring further adjuvant therapy.

This clinical report describes durable control of disease in a postmenopausal patient receiving hemodialysis and letrozole plus lapatinib since the diagnosis of HER2-positive, estrogen receptor-positive liver metastasis from breast cancer after anastrozole plus trastuzumab failure.

Background: Tumor phenotype may change during breast cancer progression. This study evaluates the prognostic impact of receptor discordance between paired primaries and recurrences., Patients and Methods: One hundred and thirty-nine patients underwent histological sampling of suspected breast cancer recurrence. All the pathology assessments [ER, PgR and human epidermal growth factor receptor 2 (HER2)] on both primaries and confirmed recurrences were performed at the same laboratory., Results: A breast cancer recurrence was confirmed in 119 cases. Rates of discordance were 13.4%, 39% and 11.8% for ER, PgR and HER2, respectively. Ninety-two patients maintained the same tumor phenotype [i.e. the same hormone receptors (HR) and HER2 status], whereas 27 (22.7%) changed during progression. The loss of HR positivity and the loss of HER2 positivity resulted in a worse post-recurrence survival (P=0.01 and P=0.008, respectively) and overall survival (OS; P=0.06 and P=0.0002, respectively), compared with the corresponding concordant-positive cases. Tumor phenotype discordance was associated with worse post-recurrence and OS (P=0.006 and P=0.002, respectively); those cases who turned into triple-negative experienced the poorest outcome, respect to the concordant group (P=0.001, OS)., Conclusions: We demonstrated for the first time an impact on OS of phenotype discordance between primary breast cancer and relapse. Among discordant cases, receptor loss resulted in the main determinant of poorer outcome.

The quality of astrophysical images produced by means of the Generalised Least Square (GLS) approach may be degraded by the presence of artificial structures, obviously not present in the sky. This problem affects in different degrees all images produced by the instruments onboard the European Space Agency (ESA) Herschel satellite. In this paper we analyse these artifacts and introduce a method to remove them. The method is based on a post-processing of GLS image that estimates and removes the artifacts subtracting them from the original image. We find that the only drawback of this method is a slight increase of the background noise which, however, can be mitigated by detecting the artifacts and by performing the subtraction only where they are detected. The efficiency of the approach is demonstrated and quantified using simulated and real data.

A quantum measurement can be described by a set of matrices, one for each possible outcome, which represents the positive operator-valued measure (POVM) of the sensor. Efficient protocols of POVM extraction for arbitrary sensors are required. We present the first experimental POVM reconstruction that takes explicit advantage of a quantum resource, i.e., nonclassical correlations with an ancillary state. A POVM of a photon-number-resolving detector is reconstructed by using strong quantum correlations of twin beams generated by parametric down-conversion. Our reconstruction method is more statistically robust than POVM reconstruction methods that use classical input states.

Aims: Eligibility for anti-human epidermal growth factor receptor 2 (HER2) treatments in breast cancer requires a correct HER2 status assessment. Testing guidelines recommend fluorescence in-situ hybridisation (FISH) for samples scored as 2+ by immunohistochemistry. This study investigates the correlation between pathological features and FISH amplification in HER2 2+ breast cancer cases., Methods: 480 HER2 2+ breast cancer samples were included. The association between tumour grade, hormone receptor status, proliferation index (Ki67) and FISH amplification, using both US Food and Drug Administration (ratio ≥2) and American Society of Clinical Oncologists/College of American Pathologists cut-offs (ratio >2.2) was evaluated., Results: 90.2% of the samples were hormone receptor positive. The median Ki67 value was 23.5%; 311 (64.8%) samples showed a Ki67 value of 15% or greater. Tumour grade was evaluable in 421 cases (87.7%), 268 (55.8%) being grade 3. FISH amplification rates were 27.5% (ratio ≥2.0) and 20.8% (ratio >2.2). Grade 3 tumours were more frequently amplified than grades 1-2 tumours: 34% versus 18% (ratio ≥2.0, p<0.001) and 27% versus 9% (ratio >2.2, p<0.001). Samples with Ki67 of 15% or greater showed higher amplification rates than low Ki67 samples: 31% versus 21% (ratio ≥2.0, p=0.022) and 25% versus 12% (ratio >2.2, p=0.003). The OR for FISH amplification was significant in the case of grade 3 and high Ki67 with both cut-offs., Conclusions: In this study, high tumour grade and high Ki67 significantly predicted FISH amplification in 480 HER2 2+ breast cancer samples.

Purpose: This is a noncomparative, randomized, phase II trial of preoperative taxane-anthracycline in combination with trastuzumab, lapatinib, or combined trastuzumab plus lapatinib in patients with human epidermal growth factor receptor 2 (HER2) -positive, stage II to IIIA operable breast cancer. The primary aim was to estimate the percentage of pathologic complete response (pCR; no invasive tumor in breast and axillary nodes)., Patients and Methods: In the three arms, chemotherapy consisted of weekly paclitaxel (80 mg/m(2)) for 12 weeks followed by fluorouracil, epirubicin, and cyclophosphamide for four courses every 3 weeks. The patients randomly assigned to arm A received a 4-mg loading dose of trastuzumab followed by 2 mg weekly; in arm B patients received lapatinib 1,500 mg orally (PO) daily; and in arm C, patients received trastuzumab and lapatinib 1,000 mg PO daily., Results: A total of 121 patients were randomly assigned. Diarrhea and dermatologic and hepatic toxicities were observed more frequently in patients receiving lapatinib. No episodes of congestive heart failure were observed. The rates of breast-conserving surgery were 66.7%, 57.9%, and 68.9% in arms A, B and C, respectively. The pCR rates were 25% (90% CI, 13.1% to 36.9%) in arm A, 26.3% (90% CI, 14.5% to 38.1%) in arm B, and 46.7% (90% CI, 34.4% to 58.9%) in arm C (exploratory P = .019)., Conclusion: The primary end point of the study was met, with a relative increase of 80% in the pCR rate achieved with chemotherapy plus trastuzumab and lapatinib compared with chemotherapy plus either trastuzumab or lapatinib. These data add further evidence supporting the superiority of a dual-HER2 inhibition for the treatment of HER2-positive breast cancer.

Lung is one of the main sites of metastatic tumors, but collision neoplasms consisting of a primary lung cancer and metastatic breast carcinoma have never been so far reported. We describe here 2 cases of primary non-small cell lung cancers (squamous cell and adenocarcinoma, respectively) colliding with metastatic breast carcinomas (ductal and lobular carcinomas, respectively). Clinico-pathologic features characterizing this challenging diagnosis and the important therapeutic implications are discussed., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Background: This study was designed to evaluate the accuracy of breast magnetic resonance imaging (MRI) and ultrasonography (US) in predicting the extent of breast residual disease after preoperative chemotherapy., Methods: Patients with stage II-III invasive breast tumors who received preoperative chemotherapy and were imaged with post-treatment MRI were included. Histopathological verification was available for all patients. The longest diameter of residual tumor measured with MRI and US has been compared with the infiltrating residual tumor size at pathologic evaluation., Results: A total of 108 patients were enrolled: 59 were imaged with both MRI and US (MRI group), and 49 were imaged with US only (non-MRI group). The non-MRI group was enrolled as an external control to avoid possible bias in the selection of patients. In the MRI group, the means of the deltas between MRI residual tumor size and pathologic size and between US and pathologic size were 0.16 cm and -0.06 cm respectively (P = not significant). Overall, a discrepancy limited in the interval from -0.5 cm to +0.5 cm compared with the pathologic size was observed in 54% and 51% of the patients with MRI and US, respectively (P = not significant). The linear correlation between the radiological measurement and pathologic tumor size was r = 0.53 for MRI and r = 0.66 for breast US. In the non-MRI group, the mean of the deltas between US residual tumor size and pathologic size was 0.06 cm, and the linear correlation was r = 0.79., Conclusions: In this series of patients, MRI and US do not show significant differences in predicting the breast residual infiltrating tumor after preoperative chemotherapy.

We present a heralded single-photon source with a much lower level of unwanted background photons in the output channel by using the herald photon to control a shutter in the heralded channel. The shutter is implemented using a simple field programable gate array controlled optical switch.

Ovarian cancer is the leading cause of gynecologic cancer-related death in Europe and the USA. The optimal treatment strategy for this malignancy includes accurate presurgical and surgical staging, optimal debulking surgery, and first-line therapy with platinum-based chemotherapy. Unfortunately, the majority of patients diagnosed with advanced ovarian cancer will eventually relapse and die. However, an appropriate management can have a major impact on survival: salvage chemotherapy can prolong survival in the majority of cases and, in selected patients, surgical cytoreduction of recurrent disease can be beneficial. The optimal timing for starting second-line therapy should be based on symptomatic or radiologic recurrence. In fact, even though cancer antigen 125 (CA 125) elevation significantly anticipates a clinical relapse, a randomized trial failed to show a survival advantage for starting second-line therapy on the basis of CA 125 elevation. This is the most solid evidence coming from a randomized trial; however, we must take into account some limitations: in this study the role of secondary cytoreduction was not considered and, at the time of study conduction, more active salvage drugs/regimens were not yet available. In the near future, a better knowledge of ovarian cancer biology, more sensitive diagnostic techniques, more accurate and less invasive surgical procedures along with the availability of new agents will further improve prognosis. In this scenario, the anticipation of salvage therapy will probably play a different role.

Since the introduction of anti-Her2 agents, the prognosis of HER2 positive breast cancer patients significantly improved. In the adjuvant setting, the monoclonal antibody trastuzumab has been evaluated in six randomized trials including more than 10,000 patients. Different modes of administration (concurrent versus sequential), durations (one year, two years or 9 weeks) and different chemotherapy regimens have been evaluated. To date, one year of trastuzumab in combination or after chemotherapy is the standard adjuvant therapy for patients with HER2 overexpressing tumors. Cardiac safety is still a major clinical issue, in particular in the treatment of early breast cancer. Several large randomized trials exploring shorter, and potentially less toxic, regimens are ongoing across several European countries. In the neoadjuvant setting, the addition of trastuzumab to chemotherapy resulted in a significantly higher activity as compared to chemotherapy alone. Unfortunately, primary and secondary resistance to trastuzumab is observed both in early and advanced disease. Several mechanisms are described as possible determinants of trastuzumab failure, and several new antiHER2 strategies are in development. Lapatinib, the HER1-2 TK inhibitor is currently approved in advanced disease after trastuzumab failure. Lapatinib is under evaluation in a large adjuvant trial, and in several neoadjuvant studies. Other molecules such pertuzumab, which binds the HER2 dimerization domain, or the pan-erbB TK inhibitor neratinib are under evaluation in the (neo)-adjuvant setting., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Ovarian cancer is the second most common gynaecological malignancy, and represents the leading cause of gynecologic cancer-related death in Europe and United States. The majority of the cases are in fact diagnosed in advanced stage, with limited chance to be cured. Optimal management of advanced ovarian cancer includes histopathological diagnosis, accurate surgical staging, debulking surgery and platinum-based chemotherapy. The combination of carboplatin and paclitaxel is commonly recognised as the standard regimen because of tolerability and activity. Intraperitoneal chemotherapy provides superior efficacy results, but its use is still controversial because of poor tolerability and compliance. Unfortunately, despite its chemosensitivity, the majority of ovarian cancer patients, including those who achieve a complete response to first-line chemotherapy, will relapse and eventually die. Among the strategies to improve patient outcome, maintenance therapy has failed to show a consistent benefit across clinical trials. Salvage second-line therapy is generally based on rechallenge with platinum in patients with platinum sensitive disease. Patients with platinum resistant/refractory might benefit from liposomal doxorubicin or topotecan. Other active cytotoxics include docetaxel, gemcitabine, etoposide and vinorelbine as well as epothilone derivatives such as patupilone which is still in development. Among targeted agents, the antiangiogenic agent bevacizumab seems extremely promising and is actively investigated in combination with first-line chemotherapy. More recently, interesting results have been obtained with the inhibitors of poly-ADP-ribose polymerase (PARP) in patients with BRCA-mutated tumors., (Copyright (c) 2009 Elsevier Inc. All rights reserved.)

Introduction and Aims: The p53 protein is a mediator of the cellular response to DNA damage. The aim of this study was to evaluate the predictive and/or prognostic value of p53 expression in relation to the molecular subtypes of breast cancer in patients treated with preoperative chemotherapy., Patients and Methods: Patients with stage II-III breast cancer were included in the study. The expression of p53 was evaluated by immunohistochemistry on the diagnostic core biopsy specimen. Patients received 4-6 courses of preoperative chemotherapy. Pathological complete response (pCR) was defined as complete disappearance of invasive tumor in the breast and axillary lymph nodes., Results: 154 patients were included in the study and the molecular subtypes of their tumors were classified as follows: triple negative 18.2%, hormone receptor positive 60.4%, and HER2 positive 21.4%. p53 was expressed in 43.5% of the patients. A significant association between p53 expression and breast cancer molecular subtypes, tumor differentiation, and proliferation was observed. pCR was achieved in 8 patients (5.2%). p53 expression, molecular subtype, and nuclear grading were significant predictors of pCR (odds ratio for pCR in patients with p53-expressing tumors 10.03, p=0.0077). In univariate analysis, the expression of p53 as well as high proliferation and lymph node involvement after preoperative chemotherapy were predictors of a worse disease-free survival. Patients with p53 positivity also had a worse overall survival. In multivariate analysis, both p53 expression and nodal status after preoperative chemotherapy were significantly associated with disease-free and overall survival: the hazard ratios for relapse and death in patients with p53-expressing versus non-p53-expressing tumors were 2.29 (p=0.015) and 7.74 (p=0.002), respectively. The hazard ratios for relapse and death in node-positive versus node-negative patients were 3.63 (p=0.003) and 3.64 (p=0.041), respectively., Conclusions: In this series of patients, p53 expression was significantly associated with markers of aggressive tumor biology, and with a higher likelihood of attaining pCR. p53 expression was a negative prognostic parameter for disease free and overall survival in univariate and multivariate analysis.

We present an actively multiplexed photon-counting detection system at telecom wavelengths that overcomes the difficulties of photon-counting at high rates. We find that for gated detectors, the heretofore unconsidered deadtime associated with the detector gate is a critical parameter, that limits the overall scalability of the scheme to just a few detectors. We propose and implement a new scheme that overcomes this problem and restores full scalability that allows an order of magnitude improvement with systems with as few as 4 detectors. When using just two multiplexed detectors, our experimental results show a 5x improvement over a single detector and a greater than 2x improvement over multiplexed schemes that do not consider gate deadtime.

The original central fatigue hypothesis suggested that fatigue during prolonged exercise might be due to higher 5-HT activity. Therefore, we examined the effects of acute administration of a selective 5-HT reuptake inhibitor (SSRI) on performance and thermoregulation. Eleven healthy trained male cyclists completed four experimental trials (two in 18 degrees C, two in 30 degrees C) in a double-blind randomised crossover design. Subjects ingested either a placebo (PLA: lactose 2 x 10 mg) or citalopram (CITAL 2 x 10 mg) on the evening before and the morning of the trial. Subjects cycled for 60 min at 55% W(max), immediately followed by a time trial (TT) to measure performance. The significance level was set at P < 0.05. Acute SSRI did not significantly change performance on the TT (18 degrees C P = 0.518; 30 degrees C P = 0.112). During recovery at 30 degrees C, core temperature was significantly lower in the CITAL trial (P < 0.012). At 30 degrees C heart rate was significantly lower after exercise in CITAL (P = 0.013). CITAL significantly increased cortisol concentrations at rest (P = 0.016), after the TT (P = 0.006) and after 15-min recovery (P = 0.041) at 30 degrees C. 5-HT reuptake inhibition did not cause significant reductions in performance. Core temperature was significantly lower only after the time trial in heat after CITAL administration. The present work failed to prove whether or not 5-HT has an exclusive role in the onset of centrally mediated fatigue during prolonged exercise in both normal and high ambient temperature.

Background: Preoperative chemotherapy (PCT) allows for in vivo testing of treatment effects on tumor and its microenvironment. Aim of this analysis was to evaluate the effect of PCT on tumor biomarker expression and to evaluate the prognostic role of treatment-induced variation of these biomarkers (molecular response)., Methods: Two hundred and twenty-one stage II-III breast cancer patients were included. The following parameters were evaluated at baseline and on surgical specimens after PCT: estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2), Ki-67, p53, human epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor 2 (VEGFR2), and apoptosis., Results: A pathological complete response was observed in 8.8% of the patients. PCT induced a significant reduction in the expression of ER, PgR, Ki-67, and apoptosis. As by multivariable model, Ki-67 > or = 15% and nodal positivity after preoperative chemotherapy (PCT) were significant predictors of worse disease-free survival [hazard ratio (HR) 3.79, P < 0.0001 and HR 2.31, P = 0.037, respectively]. Ki-67 > or = 15% after PCT was also a significant predictor of overall survival (HR 3.75, P = 0.013). On the basis of these two parameters, patients were classified into three groups: (i) low risk (negative nodes and Ki-67 <15%), (ii) intermediate risk (nodal positivity or Ki-67 > or = 15%), and (iii) high risk (nodal positivity and Ki-67 > or = 15%). As compared with the low-risk group, the HRs for recurrence were 3.1 and 9.3 for the intermediate- and high-risk group, respectively (P = 0.0001); the HRs for death were 2.4 and 6.5 for the intermediate- and high-risk group, respectively (P = 0.042)., Conclusions: Ki-67 and nodal status have been used to generate a simple and easily reproducible prognostic model, able to discriminate patients with worse prognosis among the heterogeneous group of women with residual disease after PCT.

Imatinib mesylate is a tyrosine kinase inhibitor used as first line treatment in chronic myeloid leukemia and gastrointestinal stromal tumor patients. Although several in vitro and animal studies demonstrated that imatinib affects immune response, few immune alterations are described in humans. We retrospectively studied hematologic and immunological parameters in 72 chronic myeloid leukemia and 15 gastrointestinal stromal tumor patients treated with imatinib at standard dosage and in 20 chronic myeloid leukemia patients treated before the introduction of imatinib in clinical practice. Both chronic myeloid leukemia and gastrointestinal stromal tumor patients developed a significant reduction of gammaglobulin and immunoglobulin serum levels. No significant hypogammaglobulinemia was observed in chronic myeloid leukemia patients in the pre-imatinib era. These data demonstrate that imatinib treatment induces hypogammaglobulinemia that can reach a severe entity in 10% of cases, both in chronic myeloid leukemia and in gastrointestinal stromal tumor patients. Prospective studies are needed to evaluate immune humoral alterations and to define the real incidence of infectious events, including viral reactivations.

Introduction: The assessment of hormone receptors (HRs) and human epidermal growth factor receptor (HER)-2 is necessary to select patients who are candidates for hormonal and anti-HER-2 therapy. The evaluation of these parameters is generally carried out in primary tumors and it is not clear if reassessment in metastatic lesions might have an impact on patient management. The primary aim of this analysis was to compare HER-2 and HR status in primary tumors versus metastatic sites in breast cancer patients., Patients and Methods: Seventy-five patients with available samples from primary tumors and paired metastases were included. HER-2 status was evaluated by immunohistochemistry (IHC) and/or fluorescence in situ hybridization (FISH); HR status was assessed by IHC., Results: Nineteen percent of primary tumors were HER-2 positive; 77% were HR positive. Sites of biopsied or resected metastases were: locoregional soft tissues (n = 30), liver (n = 20), central nervous system (n = 5), bone (n = 5), pleura (n = 4), distant soft tissues (n = 3), abdomen (stomach, colon, peritoneum) (n = 3), bronchus (n = 3), and bone marrow (n = 2). For paired metastases, the HER-2 status was unchanged in 84% of cases; two patients changed from positive to negative, while 10 patients converted from negative to positive (agreement, 84%; kappa = 0.5681). A change in HR status was observed in 16 cases (21%): nine cases from positive to negative and seven cases from negative to positive (agreement, 78.7%; kappa = 0.4158)., Conclusions: Further studies are necessary to better define the level of discordance in HER-2 or HR status between primary tumors and paired metastases. However, a biopsy of metastatic disease can be recommended, if feasible with minimal invasiveness, because treatment options might change for a significant proportion of patients.

Purpose: To evaluate the in vivo effect of adding gefitinib to preoperative chemotherapy on the EGFR-dependent p42/44 MAPK in operable breast cancer (BC) patients. Secondary aims: to evaluate EGFR, (p)-EGFR, Ki67, apoptotic index (TUNEL test) and VEGFR2 expression from baseline to surgery, percentage of pathologic complete response (pCR), and toxicity., Patients and Methods: 90 patients with stage II-IIIA BC have been randomized to receive epirubicin 90 mg/sqm and paclitaxel 175 mg/sqm on day 1 plus: gefitinib 250 mg daily from day 5 to 16 (Arm A, intermittent), gefitinib 250 mg daily from day 1 to 21 (Arm B, continuous), or placebo (Arm C). Treatment plan: 4 courses every 3 weeks, followed by surgery., Results: After preoperative therapy, 86/90 patients underwent surgery; 46 patients (51%) received breast conservative surgery. A pCR was observed in 4 patients. No significant differences in the expression of p42/44 MAPK, EGFR, (p)-EGFR, VEGFR2, proliferation index and apoptosis were observed comparing the combined Arms A + B vs C, and comparing Arm A vs B. Hematologic toxicities were not significantly different comparing Arms A + B vs Arm C, and comparing Arm A vs B. Significantly higher skin and mucosal toxicities were observed when comparing the two gefitinib Arms (A + B) vs Arm C (32% vs 9.6%, P = 0.018; 57% vs 29%, P = 0.009 respectively), while no significant differences were observed comparing Arm A vs B., Conclusion: Adding gefitinib to chemotherapy did not result in different effects on the EGFR-dependent pathway, proliferation, apoptosis and VEGFR2 expression as compared to placebo, while enhancing skin and mucosal toxicity. The two schedules of gefitinib (intermittent vs continuous) did not result in different biologic effects.

Many hormone receptor-positive tumors show primary or acquired resistance, possibly because of a crosstalk with other growth factor-related transduction pathways (mainly epidermal growth factor receptor family related). The LETLOB study is a European multicenter, placebo-controlled, randomized phase II trial in postmenopausal patients with hormone-sensitive, HER2-negative, stage II-IIIA (T > 2 cm, N0-1, M0) breast cancer, in which letrozole or the combination of letrozole plus lapatinib will be administered for 6 months before surgery. Clinical endpoints (primary [ultrasonographic objective response], secondary [rate of pathologic complete response and of conservative surgery, safety, and time to treatment failure], and biologic [inhibition of intermediate and final biomarkers of the proliferative and apoptosis pathways and gene profile correlation with response]) will be evaluated.

Purpose: To retrospectively evaluate the clinical, pathologic, and helical computed tomographic (CT) and magnetic resonance (MR) imaging findings of hepatocellular carcinoma (HCC) in patients with nonalcoholic fatty liver disease (NAFLD)., Materials and Methods: Institutional review board approval was obtained for this study; the need for patient informed consent was waived. Clinical, pathologic, and imaging findings were retrospectively evaluated in 22 men (mean age, 64.5 years) with HCC and NAFLD. Helical CT and MR images were reviewed for morphologic features such as tumor size, margins, necrosis, and degree of enhancement., Results: Obesity, diabetes, and hypertension were common findings and were observed in 12 (55%), 14 (64%), and 13 (59%) of the 22 patients, respectively. The serum alpha-fetoprotein level was elevated in eight patients (36%). All patients had pathologic evidence of NAFLD. HCC was well-differentiated in seven patients, moderately differentiated in 11, and poorly differentiated in four. Large tumors (mean diameter, 8.4 cm) were depicted at CT and/or MR imaging in all patients. Twenty-one patients had a solitary or dominant mass. At imaging, tumor margins were well defined in 17 patients, with a smooth surface in 17, and there was evidence of a tumor capsule in 15. Necrosis was depicted in 16 patients. There was no evidence of calcifications, central scar, fat, or abdominal lymphadenopathy. CT was performed in 20 patients. HCC was hypoattenuating on unenhanced CT scans in 14 patients, heterogeneously hyperattenuating in the arterial phase in 20, and hypoattenuating in the portal phase in 14. MR imaging was performed in 16 patients. HCC was hyperintense compared with liver parenchyma at T2-weighted MR imaging in all 16 patients, hypointense at T1-weighted imaging in 14, heterogeneously hyperintense at arterial phase T1-weighted imaging in 16, and hypointense at portal phase T1-weighted imaging in 14., Conclusion: HCC in patients with NAFLD is more likely to manifest as a large solitary or dominant mass characterized by smooth and possibly encapsulated margins, necrosis, and hypervascularity.

We demonstrate a method to reconstruct the joint photon statistics of two or more modes of radiation by using on/off photodetection performed at different quantum efficiencies. The two-mode case is discussed in detail, and experimental results are presented for the bipartite states obtained after a beam splitter fed by a single photon state or a thermal state.

Objective: It is important to recognize the imaging characteristics of peliosis hepatis because peliotic lesions may mimic several different types of focal hepatic lesions, Conclusion: We illustrate the spectrum of imaging findings of peliosis hepatis, including sonography, CT, MR, and angiography.

Background: Based on the relevant literature, the aim of this study was to analyze the psychosocial characteristics of patients with vasovagal syncope and to evaluate these factors as possible etiopathological components., Methods: The study sample consisted of 60 subjects divided as follows: the syncope group (n = 30) and the control group (n = 30, without prominent diseases). The two groups were matched with regard to age, sex, education and civil status. Each participant filled in the Twenty-Item Toronto Alexithymia Scale, acceptance of emotions scale, profile of mood state, attachment style questionnaire, and childhood traumatic events scale., Results: The syncope group showed a higher number of somatic diseases (p < 0.0002) and a higher drug use (p < 0.0001) than the control group. Moreover, the syncope group showed higher scores at the childhood traumatic events scale (p < 0.04) and more difficulties in emotion regulation (p < 0.02). The syncope group also showed higher scores at the need for approval scale (p < 0.0006) and lower scores at the confidence scale (p < 0.02) of the attachment style questionnaire, which reflect an insecure style of relationship with others., Conclusions: A high number of traumatic events in infancy and adolescence, difficulties in the expression of emotions and an insecure style of relationship seem to characterize subjects with vasovagal syncope. These data show that syncope could be at least partiality due to a relational and emotional imbalance that finds expression through the body in the presence of insufficient mental processing. Treatment of this syndrome should therefore take these aspects into consideration.

Purpose: To determine, by using multi-detector row helical computed tomography (CT), the added value of obtaining unenhanced and delayed phase scans in addition to biphasic (hepatic arterial and portal venous phases) scans in the detection of hepatocellular carcinoma (HCC) in patients with cirrhosis., Materials and Methods: Local ethical committee approval and patient consent were obtained. One hundred ninety-five patients (129 men, 66 women; mean age, 61 years; age range, 39-78 years) with 250 HCCs underwent multi-detector row helical CT of the liver. A quadruple-phase protocol that included unenhanced, hepatic arterial, portal venous, and delayed phases was performed. Analysis of images from hepatic arterial and portal venous phases combined, hepatic arterial and portal venous phases with the unenhanced phase, hepatic arterial and portal venous phases with the delayed phase, and all phases combined was performed separately by three independent radiologists. Relative sensitivity, positive predictive value, and area under the receiver operating characteristic curve (A(z)) were calculated for each reading session., Results: Mean sensitivity and positive predictive values, respectively, for HCC detection were 88.8% (666 of 750 readings) and 97.8% (666 of 681 readings) for the combined hepatic arterial and portal venous phases, 89.2% (669 of 750 readings) and 97.8% (669 of 684 readings) for hepatic arterial and portal venous phases with the unenhanced phase, 92.8% (696 of 750 readings) and 97.3% (696 of 715 readings) for hepatic arterial and portal venous phases with the delayed phase, and 92.8% (696 of 750 readings) and 97.3% (696 of 715 readings) for all four phases combined. The reading sessions in which delayed phase images were available for interpretation showed significantly (P < .05) superior sensitivity and A(z) values., Conclusion: Unenhanced phase images are not effective for HCC detection. Because of the significant increase in HCC detection, a delayed phase can be a useful adjunct to biphasic CT in patients at risk for developing HCC., ((c) RSNA, 2005.)

The case of a female patient with abdominal pain, fever and dyspnea appeared abruptly, is reported. Two days previously the patient underwent endoscopic colic polypectomy. Preliminary abdominal and chest X-ray showed colic and tenual air-fluid levels, a modest amount of pneumomediastinum and soft tissue emphysema of the neck. The cause of the latter finding was referable to five sites of origin: the lung parenchyma, mediastinal airways, the esophagus, the neck and the abdominal cavity. For symptom worsening thoracoabdominal CT was performed. It confirmed the pneumomediastinum and soft tissue emphysema of the neck and presence of intra and retroperitoneal free air as for perforation. Colonoscopy is a routine procedure in the diagnosis and therapy of colonopathies, but colic iatrogenic perforation is a dangerous complication not to be underestimated.

Background and Aims: We prospectively compared the performance of low-dose multidetector computed tomographic colonography (CTC) without cathartic preparation with that of colonoscopy for the detection of colorectal polyps., Methods: A total of 203 patients underwent low-dose CTC without cathartic preparation followed by colonoscopy. Before CTC, fecal tagging was achieved by adding diatrizoate meglumine and diatrizoate sodium to regular meals. No subtraction of tagged feces was performed. Colonoscopy was performed 3-7 days after CTC. Three readers interpreted the CTC examinations separately and independently using a primary 2-dimensional approach using multiplanar reconstructions and 3-dimensional images for further characterization. Colonoscopy with segmental unblinding was used as reference standard. The sensitivity of CTC was calculated both on a per-polyp and a per-patient basis. For the latter, specificity, positive predictive values, and negative predictive values were also calculated., Results: CTC had an average sensitivity of 95.5% (95% confidence interval [CI], 92.1%-99%) for the identification of colorectal polyps > or =8 mm. With regard to per-patient analysis, CTC yielded an average sensitivity of 89.9% (95% CI, 86%-93.7%), an average specificity of 92.2% (95% CI, 89.5%-94.9%), an average positive predictive value of 88% (95% CI, 83.3%-91.5%), and an average negative predictive value of 93.5% (95% CI, 90.9%-96%). Interobserver agreement was high on a per-polyp basis (kappa statistic range, .61-.74) and high to excellent on a per-patient basis (kappa statistic range, .79-.91)., Conclusions: Low-dose multidetector CTC without cathartic preparation compares favorably with colonoscopy for the detection of colorectal polyps.

Purpose: To compare the performance of lower-dose multi-detector row helical computed tomographic (CT) colonography with that of conventional colonoscopy in the detection of colorectal lesions., Materials and Methods: One hundred fifty-eight patients underwent multi-detector row helical CT colonography (beam collimation, 4 x 2.5 mm; table feed, 17.5 mm/sec; voltage, 140 kV; and effective dose, 10 mAs) followed by conventional colonoscopy. Conventional colonoscopy served as the reference standard. Two radiologists interpreted CT colonographic images to assess the presence of polyps or carcinomas. Sensitivity was calculated on both a per-polyp and a per-patient basis. In the latter, specificity and positive and negative predictive values were also calculated. Weighted CT dose index was calculated on the basis of measurements obtained in a standard body phantom. Effective dose was estimated by using commercially available software., Results: CT colonography correctly depicted all 22 carcinomas (sensitivity, 100%) and 52 of 74 polyps (sensitivity, 70.3%). Sensitivity for detection was 100% in all 13 polyps 10 mm or larger in diameter, 83.3% in 20 of 24 polyps 6-9 mm, and 51.3% in 19 of 37 lesions 5 mm or smaller. With regard to the per-patient analysis, CT colonography had a sensitivity of 96.0%, a specificity of 96.6%, a positive predictive value of 94.1%, and a negative predictive value of 97.7%. The total weighted CT dose index for combined prone and supine acquisitions was 2.74 mGy. The simulated effective doses for complete CT colonography were 1.8 mSv in men and 2.4 mSv in women., Conclusion: Lower-dose multi-detector row helical CT colonography ensures substantial dose reduction while maintaining excellent sensitivity for detection of colorectal carcinomas and polyps larger than 6 mm in diameter.

Our objective was to evaluate the feasibility of ultra-low-dose scanning for multislice CT colonography in the detection of colorectal lesions. Twenty-seven patients (14 men, 13 women) with clinical indication for conventional colonoscopy were recruited. Multislice spiral CT (Somatom Plus 4 Volume Zoom, Siemens, Germany) examinations were performed after standard oral colonoscopic preparation and colonic distension with room air. Images were acquired using 2.5-mm collimation, 3.0-mm slice thickness, standard reconstruction kernel, 140 kVp, and 10 mAs. Supine and prone acquisitions were obtained in all patients. Images were analyzed on a workstation by two gastrointestinal radiologists. Conventional colonoscopy was performed on the same day in all patients and represented the standard of reference. Total radiation exposure was also calculated. All colorectal cancers were correctly identified at CT colonography (9 of 9, sensitivity 100%). The CT colonography also detected 10 of 12 polyps (overall sensitivity 83.3%). Based on polyp diameter, the sensitivity for the detection of polyps 10 mm or larger was 100% (3 of 3); between 6 and 9 mm, 100% (3 of 3); and 5 mm or smaller, 66.6% (4 of 6). Total radiation exposure for prone and supine acquisitions combined was 1.7 mSv (for men) and 2.3 mSv (for women). Although preliminary, our experience suggests that ultra-low-dose scanning for multislice CT colonography is feasible. This technique provides a sensitivity comparable to that of previous experiences with CT colonography but with a 40-70% reduction of the radiation dose delivered to patients.

Since its presentation by Mirizzi in 1931, the role of intraoperative cholangiography (ICHO) has been controversial and has become an argument even more disputed with the introduction of laparoscopic cholecystectomy (VLC) in 1988. The Authors reviewed their experience to determine the most appropriate use of ICHO during VLC on the basis of a retrospective analysis of cases of selective ICHO. From December 1991 to January 2001, 597 patients, 552 elective procedure and 45 emergency procedure, were reviewed. Of 552 patients 62 presented with at least one diagnostic criterion for symptomatic gallstone disease and were treated by means of ERCP completed with endoscopic sphincterectomy (ES) when a stone of the common bile duct was found, while the remaining 490 patients underwent VLC; a total of 10 ICHO were performed, two of which in the ERCP group and 8 in the VLC group. The 45 patients treated in emergency underwent VLC; in 43 cases ICHO was performed. Of all patients, there were 2 cases of common bile duct injuries (0.33%) and in both cases ICHO was not performed. A cholangiogram added 27 min to the average duration of surgery. On the basis of both the literature and Authors' experience, it can be stated that the routine use of ICHO is not useful to reduce bile duct injuries, while it significantly increases the cost of the surgical procedure due to the increase of average operative time. The use of ICHO seems to be effective to demonstrate clinically unsuspected choledocholitiasis, although, at present, the real clinical advantage deriving from the detection of these stones is not clear. The Authors conclude that further prospective, randomized studies are necessary to assess the precise role of ICHO with regard to VLC.

The aim of our study was to assess whether contrast-enhanced CT colonography is a feasible alternative to both conventional colonoscopy and liver ultrasonography in the follow-up program of colorectal cancer patients. Thirty-five patients, surgically treated for colorectal cancer, underwent a follow-up program that included physical examination, carcinoembryonic antigen serum assay, conventional colonoscopy, liver ultrasonography, and chest X-ray. For these patients, we added a yearly contrast-enhanced CT colonography. All CT examinations were performed with a high-resolution protocol using a multidetector spiral CT scanner (Siemens, Erlangen, Germany) prior to and after the administration of 130 ml of i.v. contrast material. Images were directly analyzed on a dedicated workstation by two radiologists to determine colonic evaluation, visualization of colonic anastomosis, presence of polyps, and extra-colonic findings. Colonic evaluation was judged as optimal in 91.7% of all colonic segments. All mechanical surgical anastomoses were visualized with CT colonography. There was no evidence of anastomotic recurrence. Seven polyps were detected in five different patients with CT colonography, with two false-positive and no false-negative examinations. Three liver metastases and two basal pulmonary nodules were also identified. Contrast-enhanced CT colonography is a feasible alternative to both conventional colonoscopy and liver ultrasonography in the follow-up of patients operated on for colorectal cancer.

Our objective was to optimize a scanning protocol for CT colonography using a multidetector scanner with an adaptive-array matrix in a phantom study. A colonic phantom with 27 simulated lesions was examined using a multidetector CT scanner (Somatom Plus 4 Volume Zoom, Siemens, Erlangen, Germany). Three scanning protocols were tested: (a) collimation 1.0 mm, slice thickness 1.0 mm; (b) collimation 2.5 mm, slice thickness 3.0 mm; and (c) collimation 2.5 mm, slice thickness 5.0 mm. Image analysis was performed by two radiologists blinded to the construction of the phantom and to imaging parameters. Sensitivity for lesion detection and image quality was assessed. Computed tomographic colonography detected 27 of 27 lesions with protocol 1 (sensitivity 100%); 26 of 27 lesions with protocol 2 (sensitivity 96.3%); and 23 of 27 lesions with protocol 3 (sensitivity 85.2%). Image quality was graded as optimal for protocol 1, good for protocol 2, and poor for protocol 3. When multidetector CT equipment with an adaptive-array matrix is used, protocols with 1.0- or 3.0-mm slice thickness have a sensitivity for the detection of lesions higher than that obtained with a 5.0-mm slice thickness. Image quality decreases progressively when the slice thickness is increased; therefore, in a clinical setting, we recommend the use of a high-resolution protocol (1.0-mm effective slice thickness) with the highest pitch value in order to reduce scanning time. Dose exposure for such a protocol if combined with 80 mAs is within the range limits recommended by the ICRP for abdominal CT scanning.

Laparoscopic cholecystectomy has become the treatment of choice for patients with symptomatic cholelithiasis. About 10-20% of patients with gallbladder stones may also present associated common bile duct stones. The management of the latter remains controversial because many different surgical strategies are available: laparoscopic treatment (laparoscopic common bile duct exploration), sequential endoscopic and laparoscopic treatment (endoscopic retrograde cholangiopancreatography/endoscopic sphincterotomy [ERCP/ES] prior to laparoscopic cholecystectomy), inverted sequential endoscopic-laparoscopic treatment (laparoscopic cholecystectomy followed by ERCP/ES), and combined endoscopic-laparoscopic treatment (laparoscopic cholecystectomy with intraoperative ERCP/ES). The aim of this study was to evaluate the efficacy and safety of sequential endoscopic-laparoscopic treatment in patients with cholecystocholedocholithiasis. We retrospectively analyzed the clinical, biochemical and radiological features of 552 patients operated on for cholelithiasis from 1991 to 2001. Common bile duct stones were suspected on the basis of increased serum levels of bilirubin, GOT, GPT, GGT, alkaline phosphatase; presence of jaundice; history of pancreatitis or cholangitis; dilated common bile duct (diameter > 8 mm) or common bile duct stones at hepatobiliary ultrasonography; presence of common bile duct stones at MR-cholangiography or at i.v. cholangiography. In patients with suspected common bile duct stones, preoperative ERCP was performed; if common bile duct stones were confirmed, ES was performed. When common bile duct stones were not suspected preoperatively, laparoscopic cholecystectomy was performed directly. Overall morbidity, mortality and conversion rates in the two groups were evaluated. Of 552 patients admitted for cholelithiasis, 62 (11.3%) underwent preoperative ERCP for suspected common bile duct stones. In 41 patients (66.1%) common bile duct stones were identified and ES with common bile duct stone extraction was performed in 40 patients (clearance: 97.5%). The overall morbidity was 16% (10 cases of post-ERCP acute pancreatitis); no mortality occurred. The conversion rate during subsequent laparoscopic cholecystectomy was 4.8%. In the group of patients with no suspicion of common bile duct stones, the conversion rate was 4.9%. Sequential treatment cannot be considered the best approach for patients with cholecystocholedocholithiasis because of its morbidity rate and the high rate of negative preoperative ERCP findings. Combined endoscopic-laparoscopic treatment seems to present more advantages, especially in term of morbidity, hospital stay and patient compliance and may, in future, be considered the treatment of choice for patients with cholecystocholedocholithiasis.

Purpose: The purpose of our study was to evaluate the efficacy of multislice spiral CT colonography: 1) in the diagnosis and staging of colorectal carcinoma; 2) in the evaluation of the proximal colon in patients with stenosing neoplasms., Materials and Methods: There were 33 patients (21 males and 12 females) with known colorectal carcinoma diagnosed by conventional colonoscopy. All patients enrolled in the study underwent both conventional colonoscopy followed by CT colonography on the same day. CT examination was performed using a multislice spiral CT scanner (Somatom Plus 4 Volume Zoom; Siemens, Erlangen, Germany). Imaging parameters were: slice collimation, 1 mm; slice thickness, 1 mm; table speed, 8 mm/sec; reconstruction interval, 1 mm; mAs, 80; kVp, 120; acquisition time, 25-32 sec. Image analysis was performed using a software package with volume-rendering capabilities (Vitrea 2.6; Vital Images, Minneapolis, USA). Image analysis consisted in the evaluation of: 1) number, size, and location of the lesions; 2) primary tumor staging. For the purposes of tumor staging, we utilized the TNM staging system. For the evaluation of parameters T and N, histologic examination on resected surgical specimens and lymph nodes served as the standard of reference. The presence of hepatic metastases was confirmed by means of partial surgical resection in patients with single metastasis or by means of intraoperative ultrasonography in patients with multiple metastases., Results: Conventional colonoscopy detected 33 carcinomas and 4 polyps and was incomplete in 9 cases (27.2% of all examinations) due to stenosing lesions. CT colonography provided adequate visualization of the whole colon in all patients with identification of 35 carcinomas (33 primary and 2 synchronous) and 10 polyps. Therefore, CT colonography correctly detected all lesions seen at conventional colonoscopy and yielded the additional identification of 2 synchronous tumors and 6 polyps located in the colon proximal to the primary stenosing neoplasm. Primary tumor staging with CT colonography was correct in 32 of 33 patients (accuracy, 96.9%), Conclusions: Multislice spiral CT colonography detected all primary neoplasms, provided correct staging of 96.9% of tumors and visualized the whole colon even in patients with stenosing lesions. Considering the current limitations of the other procedures and the possibility of assessing both the colon and the extracolonic structures, multislice spiral CT colonography can be proposed as the initial diagnostic modality for pre-operative evaluation of patients with colorectal carcinoma.

Recent results from BOOMERANG-98 and MAXIMA-1, taken together with COBE DMR, provide consistent and high signal-to-noise measurements of the cosmic microwave background power spectrum at spherical harmonic multipole bands over 2

We describe a measurement of the angular power spectrum of anisotropies in the cosmic microwave background (CMB) at scales of 0&fdg;3 to 5 degrees from the North American test flight of the Boomerang experiment. Boomerang is a balloon-borne telescope with a bolometric receiver designed to map CMB anisotropies on a long-duration balloon flight. During a 6 hr test flight of a prototype system in 1997, we mapped more than 200 deg(2) at high Galactic latitudes in two bands centered at 90 and 150 GHz with a resolution of 26&arcmin; and 16&farcm;5 FWHM, respectively. Analysis of the maps gives a power spectrum with a peak at angular scales of 1 degrees with an amplitude 70 µK(CMB).

We use the angular power spectrum of the cosmic microwave background, measured during the North American test flight of the Boomerang experiment, to constrain the geometry of the universe. Within the class of cold dark matter models, we find that the overall fractional energy density of the universe Omega is constrained to be 0.85

Objective: A circadian rhythm of blood pressure has been demonstrated both in subjects who are physically active during the day and in those confined to bed. The study of the circadian rhythm of arterial flow and peripheral resistance, on the other hand, is limited to pioneer experiments. This paper is aimed at demonstrating that leg peripheral resistance has circadian fluctuations which are modulated by spinal neural traffic., Methods: Eleven normal (able-bodied) human subjects and 11 patients with spinal transection due to spinal cord injury (SCI) were studied. They were confined to bed for 24 h. Blood pressure and heart rate were monitored every 15 min with an automatic device and leg flow with an automatic strain-gauge plethysmograph synchronised to the pressurometer. Peripheral resistance was calculated at the same intervals., Results: In able-bodied subjects leg resistance was significantly higher during waking hours (when the sympathetic system is more activated) than during sleep, while in subjects with spinal cord injury no difference was detected between day-time and night-time., Conclusions: The circadian rhythm is controlled by adrenergic fibres transmitted via the spinal cord.

Fifty-six children with chronic asthma, 6 to 14 years of age, were studied to evaluate bronchoconstrictive airway responses after ingestion of varying doses of potassium bisulfite administered in one occasion in capsule and in another occasion in solution. With methacholine challenge before and after metabisulfite (MBS) provocation, the relationship of bronchoconstrictive responses and bronchial hyperreactivity was evaluated. Positive bronchoconstrictive responses were observed in only four children after the ingestion of a maximum dose of MBS in capsule and in two children after the ingestion of different doses of MBS solution. A high reactivity to methacholine challenge was present in all the reactive children. After MBS challenge, no additional changes in bronchial reactivity were observed either in the reactors or nonreactors.

We present a case of a girl with Poland's Syndrome (absence of pectoral muscle and syndactyly) associated with Moebius Syndrome. More abnormalities, especially visceral, may be associated with it and therefore the clinician must know and identify them as soon as possible. We underline the importance of a precocious correction of the hand's abnormalities in order to avoid changes in the corporal pattern otherwise not correctible later. A retard in surgical treatment will produce a failure like in our patient.

The authors report about their first study of the detrusor activity modifications induced by electrical stimulation of the posterior tibial nerve in six patients with neurogenic bladder. The results suggest that this new application inhibit detrusor activity.