[Bifocal lung cancer: the same histology?]. / Cancer bronchique bifocal: une même histologie?

Whereas synchronous lung cancer is rare, synchronous small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) are exceptional. The authors report the case of a 61-year-old man with synchronous unilateral adenocarcinoma and small cell lung cancer, raising the question as to the need for the histology of all of the lesions in the same lobe or same lung as well as the treatment. The medical history, biology, CT and (18)F-FDG TEP-CT did not support a diagnosis of synchronous lung cancer. The prognosis was poor and only surgery could improve the prognosis. This is a rare case and illustrates the difficulty in the diagnosis of multiple lung cancer and the difficulty in treating synchronous lung cancer with different histologies (SCLC and NSCLC).

Predicting the site of origin of tumors by a gene expression signature derived from normal tissues.

Multiple expression signatures for the prediction of the site of origin of metastatic cancer of unknown primary origin (CUP) have been developed. Owing to their limited coverage of tumor types and suboptimal prediction accuracy on distinct tumors, there is still room for alternative CUP gene expression signatures. Whereas in past studies, CUP classifiers were trained solely on data from tumor samples, we now use expression patterns from normal tissues for classifier training. This approach potentially avoids pitfalls related to the representation of genetically heterogeneous tumor subtypes during classifier training. Two expression data sets of normal human tissues have been reanalyzed to derive an expression signature for liver, prostate, kidney, ovarian and lung tissues. In reciprocal validation, classifiers trained on either data set achieved overall accuracies greater than 97%. Classifiers trained on combined expression data from both normal tissue data sets were able to predict the site of origin in a cohort of 652 primary tumors with approximately 90% accuracy. Prediction accuracies of primary cancer-based classifiers were in the same range, as determined by cross-validation on this cohort. For individual tumor types, normal tissue-based classifiers achieved sensitivities in the range of 64-99% and specificities in the range of 92-100%. Primary origins for 12 of 20 metastases were predicted correctly, with false predictions highlighting the need for accurate sample preparation to avoid contaminations by metastases-surrounding tissue. We conclude that gene expression patterns of normal tissues harbor phenotypic information that is retained in tumors and can be sufficient to recover the type of primary tumor from expression patterns alone.

[Pulmonary malignant melanoma: primary or metastatic?]. / Mélanome malin pulmonaire: primitif ou métastase ?

Primary pulmonary malignant melanoma is rare (0.01% of pulmonary cancers); only 25 cases are published in the literature. The diagnosis of primary pulmonary malignant melanoma is controversial, the pathogenesis is unknown and a pulmonary metastasis from a mucocutaneous melanoma is the main differential diagnosis. The diagnosis is based on the strict application of the Jensen criteria published in 1967. We report the case of an asymptomatic 82-year-old man presenting with a fortuitously discovered primary pulmonary malignant melanoma according to the Jensen criteria and treated by lobectomy (cT1N0M0). Surgery seems to be the gold standard treatment on account of the poor sensitivity of melanoma to chemotherapy and radiotherapy. Surgical resection and the absence of nodal involvement suggest a good prognosis even though the small number of cases does not produce useful statistical data. This observation raises the question of (18)FDG CT-PET in this situation, particularly of the whole body, by extrapolation from the recommendations in mucocutaneous melanoma. The lack of increased uptake on (18)FDG CT-PET could be a new paraclinical diagnostic criterion to add to the clinical criteria of Jensen. This report is the first, which shows the results of (18)FDG CT-PET (standard and whole-body) under this situation.

WITHDRAWN: Predicting the site of origin of tumors by a gene expression signature derived from normal tissues.

Multiple expression signatures for the prediction of the site of origin of metastatic cancers of unknown primary origin (CUP) have been developed. Owing to their limited coverage of tumor types and suboptimal prediction accuracy on distinct tumors there is still room for alternative CUP gene expression signatures. Whereas in past studies CUP classifiers were solely trained on data from tumor samples, we now use expression patterns from normal tissues for classifier training. This approach potentially avoids pitfalls related to the representation of genetically heterogeneous tumor subtypes during classifier training. Two expression data sets of normal human tissues have been reanalysed to derive an expression signature for liver, prostate, kidney, ovarian and lung tissues. In reciprocal validation classifiers trained on either data set achieved overall accuracies greater than 97%. Classifiers trained on combined expression data from both normal tissue data sets were able to predict the site of origin in a cohort of 652 primary tumors with approximately 90% accuracy. Prediction accuracies of primary cancer-based classifiers were in the same range as determined by cross-validation on this cohort. For individual tumor types, normal tissue-based best-centroid classifiers achieved sensitivities ranging from 71 to 99% and specificities ranging from 91 to 99%. Primary origins for 12 of 20 metastases were predicted correctly with false predictions highlighting the need for accurate sample preparation to avoid contaminations by metastases-surrounding tissue. We conclude that gene expression patterns of normal tissues harbor phenotypic information that is retained in tumors and can be sufficient to recover the type of a primary tumor from expression patterns alone.Oncogene advance online publication, 16 November 2009; doi:10.1038/onc.2009.398.

[Erlotinib and nonsmall cell lung cancer with brain metastases: a case study with a complete and prolonged response over 17 months]. / Erlotinib et métastases cérébrales d'un cancer bronchique non à petites cellules : une réponse complète et prolongée de 17 mois.

The prognosis of stage IV nonsmall cell lung cancer, in particular with brain metastases, is extremely poor. The impact of targeted therapy, in particular erlotinib, on patient survival has still not been determined. The authors report the case of a patient diagnosed with nonsmall cell lung cancer with bone and brain metastases. The patient presented a complete cerebral response for 17 months with erlotinib prescribed as a third line therapy.

[Dyspnea in lung cancer]. / La dyspnée dans le cancer du poumon.

Dyspnea is a subjective symptom defined as an experience of uncomfortable and difficult breathing which strongly affects the quality of life. It is the most common symptom in lung cancer but its physiopathology remains unclear. Dyspnea is due to cancer itself, specific therapies or comorbidities. To evaluate intensity of dyspnea, analogue visual and verbal rating scales need to be preferred. Diagnosis of underlying cause, based on rational and non invasive strategy is needed to perform effective treatment if possible. Despite its frequency, few therapies are really effective, except nonpharmacologic measures: only morphine can be actually recommend, especially with naive patients. In palliative cases, if dyspnea is uncontrolled, benzodiazepine can be used and may represent ethic approach.

[Lymphadenopathy and absences]. / Lymphadenopathie und Absenzen.

A 6-year-old boy presented with deterioration of general well-being during several weeks, headache and swelling of lymph nodes in the neck. In addition, the parents reported brief episodes resembling typical absence seizures. Serological tests and the examination of cerebrospinal fluid revealed neuroborreliosis. At the same time, electroencephalography showed characteristic patterns of absence epilepsy. The boy's condition improved rapidly during a 2-week course of intravenous ceftriaxone and after initiation of antiepileptic therapy. To our knowledge, absence epilepsy has not previously been reported in association with neuroborreliosis. We consider the two conditions to be coincidental.

[A case of atypical pericarditis]. / Une péricardite atypique.

INTRODUCTION: An acute viral pericarditis may reveal a congenital pericardial abnormality. CASE HISTORY: We report the case of a young man of 29 years in whom the development of rapidly progressive dyspnoea and fever led to the echocardiographic diagnosis of a pericardial tumour. The thoracic CT scan showed a mass arising in the superior mediastinum with no evidence of spread. Surgical exploration allowed the excision of a soft mutilobular mass adherent only to the aorta. Histological examination revealed an intrapericardial bronchogenic cyst. CONCLUSION: After a review of bronchogenic cysts we point out the properties of this rare intra-pericardial localisation, one of which is the frequently observed secretion of CA 19-9.

[Positron emission tomography in the diagnosis and follow up of non-small cell lung cancer]. / 18F-FDG-TEP : sa place dans le diagnostic et la surveillance du cancer bronchique non à petites cellules.

In the space of a few years 18F-FDG PET scanning has acquired a place in the management of all stages of the clinical care of patients with lung cancer. Its contributions are being more and more precisely understood during the assessment of mediastinal and metastatic extension and it carries the hope of better therapeutic management and surveillance.

Differential expression of genes encoding tight junction proteins in colorectal cancer: frequent dysregulation of claudin-1, -8 and -12.

BACKGROUND AND AIMS: As integral membrane proteins, claudins form tight junctions together with occludin. Several claudins were shown to be up-regulated in various cancer types. We performed an expression analysis of genes encoding tight junction proteins to display differential gene expression on RNA and protein level and to identify and validate potential targets for colorectal cancer (CRC) therapy. PATIENTS AND METHODS: Amplified and biotinylated cRNA from 30 microdissected CRC specimen and corresponding normal tissues was hybridized to Affymetrix U133set GeneChips. Quantification of differential protein expression of claudin-1, -8 and -12 between normal and corresponding tumour tissues was performed by Western blot analyses. Paraffin-embedded CRC tissue samples, colon cancer cell lines and normal tissue microarray were analysed for protein expression of claudin-1 by immunohistochemistry (IHC). RESULTS: Claudin-1 (CLDN1) and -12 (CLDN12) are frequently overexpressed in CRC, whereas claudin-8 (CLDN8) shows down-regulation in tumour tissue on RNA level. Quantification of proteins confirmed the overexpression of claudin-1 in tumour tissues, whereas changes of claudin-8 and -12 were not significantly detectable on protein level. IHC confirmed the markedly elevated expression level of claudin-1 in the majority of CRC, showing membranous and intracellular vesicular staining. CONCLUSIONS: Differential expression of genes encoding claudins in CRC suggests that these tight junction proteins may be associated to and involved in tumorigenesis. CLDN1 is frequently up-regulated in large proportion of CRC and may represent potential target molecule for blocking studies in CRC.

Genetic analysis of the LGI/Epitempin gene family in sporadic and familial lateral temporal lobe epilepsy.

Mutations in the LGI1/Epitempin gene cause autosomal dominant lateral temporal lobe epilepsy (ADLTE), a partial epilepsy characterized by the presence of auditory seizures. However, not all the pedigrees with a phenotype consistent with ADLTE show mutations in LGI1/Epitempin, or evidence for linkage to the 10q24 locus. Other authors as well as ourselves have found an internal repeat (EPTP, pfam# PF03736) that allowed the identification of three other genes sharing a sequence and structural similarity with LGI1/Epitempin. In this work, we present the sequencing of these genes in a set of ADLTE families without mutations in both LGI1/Epitempin and sporadic cases. No analyzed polymorphisms modified susceptibility in either the familial or sporadic forms of this partial epilepsy.

[Low grade pulmonary sarcoma preceding the discovery of a uterine primary]. / Sarcome pulmonaire de bas grade précédant la découverte d'un primitif utérin.

INTRODUCTION: Low grade pulmonary sarcomas are very rare tumours. We report the case of a low grade sarcoma of the lung occurring two years prior to the finding of a uterine primary. CASE REPORT: Complete surgical excision of a low grade pulmonary sarcoma was performed. The initial search for dissemination was negative. Two years later a follow-up scan discovered a uterine mass as well as a para-aortic shadow that proved to be the primary tumour (low grade uterine sarcoma) and a metastasis. CONCLUSION: This is the second case of a pulmonary metastasis discovered before a primary low grade uterine sarcoma. The first was found during the investigation of a pulmonary sarcoma. The main differential diagnosis to consider is metastatic leiomyosarcoma. In both cases their finding justifies the search for a uterine primary by immunohistochemical examination for oestrogen and progesterone receptors as well as pelvic ultrasound or even magnetic resonance imaging.

Inactivation of Bacillus subtilis spores and formation of bromate during ozonation.

Inactivation of B. subtilis spores with ozone was investigated to assess the effect of pH and temperature, to compare the kinetics to those for the inactivation of C. parvum oocysts, to investigate bromate formation under 2-log inactivation conditions, and to assess the need for bromate control strategies. The rate of B. subtilis inactivation with ozone was independent of pH, decreased with temperature (activation energy of 42,100 Jmol(-1)), and was consistent with the CT concept. B. subtilis was found to be a good indicator for C. parvum at 20-30 degrees C, but at lower temperatures B. subtilis was inactivated more readily than C. parvum. Bromate formation increased as both pH and temperature increased. For water with an initial bromide concentration of 33 microgl(-1), achieving 2-logs of inactivation, without exceeding the 100 microg l(-1) bromate standard, was most difficult at 30 degrees C for B. subtilis and at midrange temperatures (10-20 degrees C) for C. partum. pH depression and ammonia addition were found to reduce bromate formation without affecting B. subtilis inactivation, and may be necessary for waters containing more than 50 microgl(-1) bromide.

The DAPIN family: a novel domain links apoptotic and interferon response proteins.

We report the discovery of a protein domain, hereafter referred to as DAPIN, in diverse vertebrate and viral proteins that is associated with tumor biology, apoptosis and inflammation. Based on a secondary structure prediction, we suggest an all-alpha fold for DAPIN, which is also adopted by apoptotic protein domains of the CARD, death domain and death effector domain type.

The roots of evil: social conditions, culture, personality, and basic human needs.

Evil actions are defined as repeated or persistent, not commensurate with provocation and causing extreme harm, at times due to repetition. Evil develops or evolves. As individuals and groups harm others, they tend to develop characteristics that make further and more intense harmdoing probable. In this article, I explore instigating conditions (difficult life conditions in a society, group conflict); cultural characteristics; the nature of evolution, with its psychological and social processes in individuals and groups; and the passivity and complicity of bystanders that lead to genocide and other collective violence. I consider the question of whether bystanders can be regarded as evil, focusing on the genocide in Rwanda as an example. I examine the socialization and experience of children and youth that lead to aggression and the subsequent evolution of aggression toward greater violence and evil. I explore the way personal characteristics and a system of relationships can lead to sexual abuse by fathers. One organizing concept in understanding the generation of violence that causes extreme harm is the frustration of basic human needs and their subsequent destructive fulfillment.

Cultural-societal roots of violence. The examples of genocidal violence and of contemporary youth violence in the United States.

Widespread violence in a society must have its origins in cultural characteristics, current societal conditions, or both. In this article, the cultural, societal, and psychological origins of two very different forms of violence are examined. A conception of the origins of genocide and mass killing is briefly presented, with the Holocaust and the violence in the former Yugoslavia as supporting evidence. Difficult life conditions give rise to scapegoating, destructive ideologies, and the evolution of increasing violence against a designated enemy. Cultural characteristics that make this process more or less probable are described. This is followed by a presentation of the socialization experiences of children that generate youth violence. To explain the increase in youth violence, the presence of difficult life conditions in the United States is noted (due primarily to substantial social change). The effects of difficult life conditions, cultural characteristics, and social conditions such as poverty and discrimination against minority groups on family life and parenting are described. Similarities and differences in the origins of the two forms of violence are examined. The role of unfulfilled or frustrated basic human needs in generating violence is stressed, and conditions and actions required to reduce violence are proposed.

[Comparison of two ELISA systems for the detection of antibodies against IBR/IPV and against enzootic bovine leukemia virus]. / Vergleich zweier ELISA Systeme zum Nachweis von Antikörpern gegen IBR/IPV sowie gegen EBL.

Sensitivity and specificity of two ELISA systems for the detection of antibodies to Bovine Herpes-virus 1 (BHV1; IBR/IPV) were tested by using 214 sera of cattle with predetermined history of BHV1 infection and freedom from BHV1 infection, respectively. With these sera as "gold-standard", the sensitivity of ELISA1 (HerdCheck: Anti-IBR) appeared to exceed 98%, whereas for ELISA2 (Checkit: Trachitest) a sensitivity of between 94 and 99.3% was determined. The specificity of ELISA1 amounted to at least 96.9%, whereas for ELISA2 it ranged apparently from 81.5 to 98.5%. When applied in routine testings of serum samples, the two ELISA systems correlated extremely well. With each test, only 3 of 1431 samples gave contradictory results. In all these cases, alternative tests suggested that the contradictions represented false-positive reactions. A similar correlation was observed when milk samples in the place of sera were probed. The serum and milk samples were additionally tested using two corresponding ELISA systems (obtained from the same manufacturers) for the detection of antibodies to Bovine Leukemia virus (BLV). The sensitivity and specificity of these tests could not be determined because of lack of samples with known history of infection. The results of the tests, however, correlated very well. Only 6 of 1431 sera reacted in a contradictory way. These observations indicate that the kits tested in this study, both for the detection of antibodies to BHV1 and to BLV, meet high quality standards. Possibilities to improve the kits were still detected.

The modern use of thoracoplasty.

Thoracoplasty is a time-honored but, at present, rarely indicated procedure for reducing thoracic cavity volume. This study reviews a series of 30 patients treated with thoracoplasty over a 14-year period (1970 through 1983). Indications were to close a persistent pleural space in 28 patients and to tailor the thoracic cavity to accept diminished lung volume concomitant with a pulmonary resection in 2 patients. Persistent pleural space, often associated with a bronchopleural fistula (24 patients), occurred after operation in 19 patients: following pulmonary resection in 17 patients, resection of mesothelioma in 1 patient, and following decortication without resection in 1. In the remaining 9 patients with a persistent pleural space, problems developed from primary lung destruction due to tuberculosis (4 patients), postpneumonic empyema (1 patient), or as late infection of a residual pleural space many years after therapeutic pneumothorax and collapse therapy for tuberculosis (4 patients). The overall success rate of thoracoplasty in eliminating intrathoracic space problems was 73%. There were 3 deaths (10%) and 5 failures to heal, representing a 33% failure in the first half of the series (to 1976) and a 17% failure rate thereafter (1 death and 1 nonhealing patient). The primary underlying disease was tuberculosis in 23 patients, 8 of whom had concomitant aspergilloma and 1, atypical tuberculosis. The failures were analyzed and reviewed to clarify the principles for the successful use of thoracoplasty. It is concluded that thoracoplasty is a rarely required salvage-type procedure applicable to moderately debilitated patients in whom it is considered desirable to eliminate open drainage.(ABSTRACT TRUNCATED AT 250 WORDS)