Esophageal stent migration leading to distal small bowel perforation.

Covered oesophageal stents are often used to treat dysphagia in patients with inoperable oesophageal cancer. Stent migration is a well-known but usually benign complication. We report the case of a patient whose esophageal stent migrated into the distal ileum with perforation hereof. A laparoscopic stent extraction and intestinal repair was necessary to treat the perforation.

Estimation of skin phototypes with optical parameters: an experimental study using newly developed fibre optic detection device.

In an experimental study (October 2010 Mannheim Germany) with 99 Caucasian volunteers, the skin colour (L*, a*, b*) and the reflectance spectra of human skin were compared to the Fitzpatrick's sun-reactive skin photo types (SPT). For this purpose, the skin colour and the reflectance spectra of human skin were determined using non-invasive method with a newly developed fibre optic detection device. The device, based on reflectance spectroscopy, was designed and optimized using a commercial optical analysis Software. By means of the measured spectra of scattered light, the colour values and the absorption spectra of the skin were calculated. Neither any of the L*, a*, b* colour values nor any of the parameters of the absorbance spectra can be used alone to assess the skin type properly. Therefore, an ordinal logistic regression analysis was performed, using the statistical computing software r, to correlate the skin types with the measured optical parameters. It turned out that the detection device combined with the extended statistical analysis gives a better estimate of skin type in respect of the measured optical parameters than a procedure with only L*, a*, b* colour values. Even with the extended methodology, the procedure gives only a rough estimation of the skin type.

Autoimmune lymphoproliferative syndrome (ALPS). Case report and family history.

Autoimmune lymphoproliferative syndrome (ALPS) is a rare disease caused by defective lymphocyte apoptosis and is characterized by non-malignant lymphoproliferation, hepatosplenomegaly, autoimmune manifestations and increased risk of both Hodgkin's and non-Hodgkin's lymphoma. Most forms of the disease are due to germ line mutations of the FAS gene and manifest during the first years of life with fluctuating lymphadenopathies, hemolysis, immune thrombocytopenia. During the second decade of life disease manifestations improve spontaneously but autoimmune problems still occur and there is an increased risk of lymphoproliferative malignancy. We describe a typical case of ALPS in a now 44 year old man, followed since the age of 2 for disease manifestations that were unclear at the beginning.

Analysis of the HLA population data (AHPD) submitted to the 15th International Histocompatibility/Immunogenetics Workshop by using the Gene[rate] computer tools accommodating ambiguous data (AHPD project report).

During the 15th International Histocompatibility and Immunogenetics Workshop (IHIWS), 14 human leukocyte antigen (HLA) laboratories participated in the Analysis of HLA Population Data (AHPD) project where 18 new population samples were analyzed statistically and compared with data available from previous workshops. To that aim, an original methodology was developed and used (i) to estimate frequencies by taking into account ambiguous genotypic data, (ii) to test for Hardy-Weinberg equilibrium (HWE) by using a nested likelihood ratio test involving a parameter accounting for HWE deviations, (iii) to test for selective neutrality by using a resampling algorithm, and (iv) to provide explicit graphical representations including allele frequencies and basic statistics for each series of data. A total of 66 data series (1-7 loci per population) were analyzed with this standard approach. Frequency estimates were compliant with HWE in all but one population of mixed stem cell donors. Neutrality testing confirmed the observation of heterozygote excess at all HLA loci, although a significant deviation was established in only a few cases. Population comparisons showed that HLA genetic patterns were mostly shaped by geographic and/or linguistic differentiations in Africa and Europe, but not in America where both genetic drift in isolated populations and gene flow in admixed populations led to a more complex genetic structure. Overall, a fruitful collaboration between HLA typing laboratories and population geneticists allowed finding useful solutions to the problem of estimating gene frequencies and testing basic population diversity statistics on highly complex HLA data (high numbers of alleles and ambiguities), with promising applications in either anthropological, epidemiological, or transplantation studies.

[Antiphospholipid antibody syndrome]. / Le syndrome des anticorps antiphospholipides.

An Antiphospholipid syndrome (APS) was diagnosed in a patient who had massive pulmonary embolisation from a right atrial thrombus. The (APS) is an autoimmune disease defined by the presence in the serum of at least one type of autoantibody known as antiphospholipid antibody (aPL) and the occurrence of at least one clinical feature from a list of potential disease manifestations, the most common of which are venous or arterial thrombosis, recurrent fetal loss and thrombocytopenia. The prevalence of APS in a series of patients from internal medicine is 2 percent. The mean age at diagnosis is 42 years. The pathogenesis of APS associated with clinical manifestations seems to result from a variety of effects of aPL on coagulation pathways,but the exact mechanism of action of aPL on these pathways is not completely understood. The APS can be primary or secondary to a disease. Thrombosis is the most frequent clinical manifestation of APS. It involves many organs, resulting on multiorgan failure: this is the catastrophic APS. The treatment is the same whether the APS is primary or secondary. It is mainly symptomatic and consists in the prevention of thrombosis at short and long-term by using aspirin and/or anticoagulants. Immunomodulating treatment can be offered but its efficiency at long-term is unproven. The mortality varies according to the etiology and the clinical manifestations. The mortality rate is 50 percent in catastrophic APS, despite treatment.

HbSC hemoglobinopathy suspected by chest x-ray and red blood cell morphology.

Thorax scan was performed for elucidation of a pulmonary problem in a Nigerian immigrant. The aspect of the vertebrae suggested sickle cell disease, of course without specification of the genotype. Routine hematological tests seemed compatible with an HbSC disease, showing typical laboratory features, namely a significant proportion of hyperchromic RBC, corresponding to secondary, non hereditary spherocytosis, presence of numerous target cells and occasional HbC crystals on Pappenheim stained blood films. The diagnosis of HbSC disease was confirmed by HPLC, iso-electric focusing and citrate agar electrophoresis of hemoglobin and by reverse phase HPLC of globin-chains. This case illustrates the importance of screening for hemoglobin anomalies as it is performed in a multiethnic country such as the Grand Duchy of Luxembourg

Donepezil for Alzheimer's disease in clinical practice--The DONALD Study. A multicenter 24-week clinical trial in Germany.

This multicenter open-label clinical trial was designed to investigate the safety and efficacy of donepezil, a selective acetylcholinesterase inhibitor, in the treatment of Alzheimer's disease (AD) in routine clinical practice in Germany. A total of 237 patients with mild-to-moderate AD were treated with donepezil for 24 weeks, 186 completed the study according to the protocol. In the completer group, mean MMSE score for efficacy showed an improvement from baseline of +1.6 points at week 12 (95% CI +1.1 to +2.1) and of +1.1 points at week 24 (95% CI +0.5 to +1.7). In more than 80% of the patients, global tolerability was rated to be very good or good. There were only insignificant effects on ECG parameters. This study confirms the results obtained in previous double-blind trials, which showed that donepezil is effective and well tolerated in patients with mild-to-moderately severe AD.

HER-2 and topo-isomerase IIalpha as predictive markers in a population of node-positive breast cancer patients randomly treated with adjuvant CMF or epirubicin plus cyclophosphamide.

BACKGROUND: The predictive role of HER-2 in node-positive breast cancer patients receiving CMF or an anthracycline-based adjuvant therapy remains unclear. In addition, topo-isomerase II alpha (topo IIalpha), as the cellular target of anthracyclines, might have value as a predictive marker. PATIENTS AND METHODS: Four hundred eighty-one archival primary tumor samples were collected among 777 patients entered into a multicenter phase III trial comparing classical CMF with epirubicin cyclophosphamide (HEC) as adjuvant therapy of node-positive breast cancer. HER-2 was evaluated by immunohistochemistry (IHC) using different antibodies (Abs). Topo IIalpha was evaluated by IHC using the Ab KiS 1. In each subgroup of patients identified by HER-2 and topo IIalpha, adjusted hazard ratios for event-free survival (EFS) and the corresponding 95% confidence intervals have been calculated for the different study comparisons. An interaction test has been performed to investigate the role of HER-2 and topo IIalpha as predictive markers. RESULTS: When HER-2 was evaluated by CB-11 and 4D5 mAbs, the EFS adjusted hazard ratios (HR) for the main study comparison HEC vs. CMF were: HER-2 positive: 0.33 (95% confidence interval (95% CI): 0.09 1.27, P = 0.08), HER-2 negative: 1.16 (95%, CI: 0.71-1.90, P = 0.56); the P-value for the interaction test was 0.10. When HER-2 was evaluated by TAB-250 + pAbl Abs, the adjusted HR for the same comparison were: HER-2 positive: 1.06 (95% CI: 0.45-2.52, P = 0.90), HER-2 negative: 0.99 (95% CI: 0.58-1.68, P = 0.97); the P-value for the interaction test was 0.84. With regard to topo IIalpha, the adjusted HR for the EFS comparison HEC vs. CMF were: topo IIalpha positive: 0.66 (95% CI: 0.32-1.36, P = 0.25), topo IIalpha negative: 1.26 (95% CI: 0.63-2.50, P = 0.51); the P-value for the interaction test was 0.13. CONCLUSIONS: This study suggests that in node-positive breast cancer patients randomly treated with CMF or an epirubicin-based regimen, the predictive value of HER-2 may vary according to the Abs used in the immunohistochemistry assay. In addition, the study supports the concept that topo IIalpha might be involved in the determination of tumor responsiveness to an anthracycline-based adjuvant therapy.

A Merkel cell carcinoma of the skin.

A 79-year old female caucasian patient presented in January 91 with a nodular lesion of the right cheek that had appeared rapidly. The histologic specimen was in favour of a primary neuroendocrine skin tumor, Merkel cell carcinoma-. In March 91, a relapsing nodule had grown up and adenopathies were found on the right parotid and sub-mandibular spaces. An aggressive polychemotherapy was performed for 6 cycles and a complete remission was obtained. In November 91 the sub-mandibular lymph node had reappeared. A complete staging was again performed. After 3 cycles of chemotherapy, a regional radiotherapy completed the treatment. With a follow-up of more than 8 years the patient stays in complete remission in April 2000.

SonoVue in transcranial Doppler investigations of the cerebral arteries.

BACKGROUND AND PURPOSE: The authors investigated the safety and diagnostic potential of a new ultrasound contrast agent (SonoVue) using transcranial color-coded duplex sonography (TCCS). METHODS: Forty patients were enrolled in a multicenter, open-label (on-site), blind (off-site), randomized, dose-ranging crossover study. SonoVue was administered as an intravenous bolus injection of 4 different dosages (0.3, 0.6, 1.2, and 2.4 mL). Efficacy was evaluated as (1) off-site assessment of global quality of the Doppler investigation (based on color or power Doppler images and spectral analysis) at baseline and following each dose of SonoVue according to a 4-point scale (from very poor to excellent imaging of blood flow) and (2) duration of clinically useful signal enhancement and color or power Doppler visualization of blood flow. Additional on-site efficacy assessments performed following each dose of SonoVue included confidence in diagnosis and global consequences of contrast enhancement on diagnosis. Safety evaluations included clinical laboratory tests, neurological examination, injection site tolerability, and incidence of adverse events and their relationship to the study agent. RESULTS: All doses of SonoVue significantly improved the global quality of Doppler examinations (P < .05). The median duration of clinically useful enhancement was dose related (P < .001) and ranged from 2 to 6 minutes at the highest dose. The administration of the contrast agent changed a nondiagnostic study to a diagnostic one in 66% of patients and increased the confidence in diagnosis in 74% of cases. No serious adverse events were recorded following SonoVue administration. The observed adverse reactions were all transient and mild in intensity. CONCLUSIONS: The results obtained from this multicenter study demonstrate that the administration of SonoVue to patients with ischemic cerebrovascular disease who undergo TCCS examination of cerebral vessels improves the visualization of intracranial arteries, providing a dose-dependent contrast enhancement and a clinically useful duration of signal enhancement related to the dose. During this multicenter study, SonoVue proved to be a safe and well-tolerated compound.

Phase III trial comparing two dose levels of epirubicin combined with cyclophosphamide with cyclophosphamide, methotrexate, and fluorouracil in node-positive breast cancer.

PURPOSE: To compare a full-dose epirubicin-cyclophosphamide (HEC) regimen with classical cyclophosphamide, methotrexate, and fluorouracil (CMF) therapy and with a moderate-dose epirubicin-cyclophosphamide regimen (EC) in the adjuvant therapy of node-positive breast cancer. PATIENTS AND METHODS: Node-positive breast cancer patients who were aged 70 years or younger were randomly allocated to one of the following treatments: CMF for six cycles (oral cyclophosphamide); EC for eight cycles (epirubicin 60 mg/m(2), cyclophosphamide 500 mg/m(2); day 1 every 3 weeks); and HEC for eight cycles (epirubicin 100 mg/m(2), cyclophosphamide 830 mg/m(2); day 1 every 3 weeks). RESULTS: Two hundred fifty-five, 267, and 255 eligible patients were treated with CMF, EC, and HEC, respectively. Patient characteristics were well balanced among the three arms. One and three cases of congestive heart failure were reported in the EC and HEC arms, respectively. Three cases of acute myeloid leukemia were reported in the HEC arm. After 4 years of median follow-up, no statistically significant differences were observed between HEC and CMF (event-free survival [EFS]: hazards ratio [HR] = 0.96, 95% confidence interval [CI], 0.70 to 1.31, P =.80; distant-EFS: HR = 0.97, 95% CI, 0.70 to 1.34, P =.87; overall survival [OS]: HR = 0.97, 95% CI, 0.65 to 1.44, P =.87). HEC is more effective than EC (EFS: HR = 0.73, 95% CI, 0.54 to 0.99, P =.04; distant-EFS: HR = 0.75, 95% CI, 0.55 to 1.02, P =.06; OS HR = 0.69, 95% CI, 0.47 to 1.00, P =.05). CONCLUSION: This three-arm study does not show an advantage in favor of an adequately dosed epirubicin-based regimen over classical CMF in the adjuvant therapy of node-positive pre- and postmenopausal women with breast cancer. Moreover, this study confirms that there is a dose-response curve for epirubicin in breast cancer adjuvant therapy.

Clinical benefit from erythropoietin.

Advances continue in erythropoietin biology, and additional data reviewed here have recently become available on complex feedback mechanisms describing the interrelations of hypoxia and its effects on anemia and tumor behavior (eg, apoptosis, angiogenesis). In addition to biology, other clinically relevant data in oncology are included and an attempt is made to identify patients who are most likely to benefit from treatment. The latter aspects will better define the profile of the target patient, probably prevent overtreatment, and improve cost-benefit ratios. Interesting data on radiotherapy results improved by increasing tissue hemoglobin have been published but will need further confirmation.

Complications and hospitalisation--duration after chemoembolisation for liver metastases.

In a retrospective study, all patients of the hemato-oncology department of the Centre Hospitalier who were treated from 1988 to 1997 by chemoembolisation for liver metastases were analysed for treatment-related hospitalisation duration, side effects and complications, in order to assess the treatment burden. Major side-effects were: pain in 17 of 29 patients, nausea in 8, vomiting in 7, persistent hickup in 3, fever in 12, a temporary confusional state in 4 patients. 1 patient experienced syncope, 2 patients developed homolateral pleral effusions, 1 patient suffered transient supraventricular arrhythmias. Major complications included 1 hemoperitoneum (under anticoagulant therapy), 1 hemorrhagic gastritis, 1 acute cholecystitis due to inflammatory tumoral choledochal obstruction and one iatrogenous acute pancreatic ischemic necrosis. Two patients died of post-embolic acute hepatic insufficiency, one 10 days, one 41 days after the last treatment session). In summary, chemo-embolisation of liver metastases is a complication-burdened treatment in a strictly palliative setting with inestimable efficacy. The treatment modalities have to be discussed with the patient beforehand and preferably in controlled study setting. Large randomised trials may indicate patients' subgroups for benefit.

[Spontaneous regression of pulmonary metastases in renal cancer]. / Régression spontanée de métastases pulmonaires d'un cancer rénal.

Spontaneous regression of lung-metastases in kidney cancer (a case report) A case is reported of a 56-year old woman with renal cell carcinoma operated and treated adjuvantly for a year with Interferon alpha. Ten months thereafter the patient had histologically proven a large pulmonary metastatic disease that regressed spontaneously. Duration of the spontaneous remission was 8 months.

Proton magnetic resonance spectroscopy of the primary motor cortex in patients with motor neuron disease: subgroup analysis and follow-up measurements.

OBJECTIVES: To determine the motor cortex degeneration in patients with amyotrophic lateral sclerosis (ALS) using proton magnetic resonance spectroscopy, and to prove that proton magnetic resonance spectroscopy is suited to monitor the course of disease with follow-up examinations. MATERIALS AND METHODS: We studied 33 patients with ALS whose conditions were diagnosed according to the El Escorial World Federation of Neurology criteria. Nine patients with ALS were followed up for up to 2 years. The control group included 20 healthy volunteers and 4 patients with multifocal motor neuropathy. Proton magnetic resonance spectroscopy determined levels of the brain metabolites N-acetylaspartate (NAA), choline, inositol-containing compounds, glutamate/glutamine, and phosphocreatine. RESULTS: Patients with ALS showed a significant reduction in the NAA-choline (P <.001) and NAA-phosphocreatine (P <.005) metabolite ratios and significantly elevated choline-phosphocreatine (P <.005) ratios compared with controls. Inositol-phosphocreatine ratios were also elevated in case patients, but the increase was less pronounced (P <.05). No differences in glutamate/glutamine-phosphocreatine ratios were detected between case patients and controls. An analysis of subgroups demonstrated less significant differences in NAA-choline metabolite ratios (P<.05), even in patients with pure lower motor neuron syndrome (suspected ALS). No changes in metabolite T1 and T2 relaxation times were observed. Patients with multifocal motor neuropathy showed normal metabolic ratios. Progressive alterations in affected metabolite ratios could be documented in the follow-up examinations. CONCLUSIONS: Spectroscopic changes in the motor cortices of patients with ALS correspond with a reduction in levels of NAA and an elevation in levels of choline and inositol compounds. Since NAA is exclusively expressed in neurons, the observed decrease of NAA reflects neuronal loss or dysfunction. Inositol and choline are associated with plasma membrane metabolism, so the release of these compounds may be related to membrane disorders.

Outcome after local intra-arterial fibrinolysis compared with the natural course of patients with a dense middle cerebral artery on early CT.

Our purpose was to relate the outcome after local intra-arterial fibrinolysis (LIF) to the natural course in middle cerebral artery (MCA) occlusion. We retrospectively studied 40 patients with a dense middle cerebral artery on early CT; 20 were treated with LIF within 6 h of onset of symptoms, 20 received "conventional" stroke therapy. The dense middle cerebral artery, which is regarded as a highly specific indicator of thromboembolic MCA occlusion, was chosen as inclusion criterion since patients with "conventional" stroke therapy were not exposed to cerebral angiography. Patients treated with LIF had a significantly better outcome using the Barthel index (P = 0.025): there was a 30% increase in the proportion of patients with minimal or no disability. Mortality, however, did not differ significantly (P = 0.7). Two fatal haemorrhages occurred in the LIF group, and one haemorrhagic transformation in the "conventional" group. Leptomeningeal collateralisation correlated significantly with outcome in the LIF group (P = 0.04). Although the relation between outcome and interval from onset of symptoms to LIF was not significant (P = 0.74), all patients treated within 3 h had an excellent outcome.

High-resolution emboli detection and differentiation by characteristic postembolic spectral patterns.

BACKGROUND AND PURPOSE: High-intensity transient signals (HITS) detected by transcranial Doppler ultrasonography correspond to microemboli in intracranial arteries. The purpose of this study was to develop new diagnostic criteria for the differentiation of these microembolic signals from artifact, based on a high-resolution analysis of Doppler power spectra in an in vitro model. METHODS: Two hundred seventy-six formed emboli, consisting of different biological and nonbiological materials and as air bubbles, were injected into a flow phantom with artificial blood vessels and perfused in a steady or a pulsatile way. Embolic passage was assessed with a modified 2.5-MHz pulsed Duplex machine and a commercial 2-MHz Doppler system. Embolic HITS were analyzed using internationally accepted criteria for the audiovisual characteristics of HITS. Doppler spectra changes associated with HITS were evaluated by means of a specially developed high-resolution analysis of Doppler raw data. RESULTS: Seventy-seven percent of all embolic events could be identified using conventional audiovisual criteria for embolic HITS. Analysis of Doppler spectra showed that all injected emboli generated high-amplitude signals with a minimum of at least 3 dB above background level. In addition, using high-resolution processing, specific changes in Doppler spectral patterns could be identified after all embolic HITS caused by solid particles. These postembolic spectral patterns were always characterized by a Doppler frequency shift decreasing in time and resembling the letter lambda (lambda). Duration and appearance of the postembolic spectral patterns were mainly influenced by the size and velocity of the embolus. Similar phenomena could not be found in case of embolism by either small air bubbles or in case of provoked artifact registration. Using a commercial Doppler system specific, we documented postembolic spectral patterns in 47% of injected emboli. CONCLUSIONS: In this study, highly specific changes in Doppler spectral patterns associated with microembolic HITS could be characterized, resulting in further criteria for the differentiation between microembolic signals and artifact in Doppler emboli detection. The sensitivity of the detection of these signals can be increased by high-resolution analysis of raw Doppler data.