Impact of cancer chemotherapy before ovarian cortex cryopreservation on ovarian tissue transplantation.

STUDY QUESTION: How efficacious is transplantation of ovarian cortex previously exposed to chemotherapy? SUMMARY ANSWER: Prior exposure to chemotherapy did not disrupt the function of cryopreserved ovarian tissue after transplantation. WHAT IS KNOWN ALREADY: Ovarian tissue cryopreservation (OTC) followed by ovarian tissue transplantation (OTT) is an efficacious technique for restoration of female fertility. At least 130 children have been born following this procedure. To date, little is known about the efficacy of OTT in patients exposed to cancer chemotherapy prior to OTC. STUDY DESIGN, SIZE, DURATION: This study evaluates the recovery of ovarian function and fertility in 31 consecutive patients who had received OTT, between 2005 and 2015. PARTICIPANTS/MATERIALS, SETTING, METHODS: Thirty one patients, wanting children, were transplanted with autologous ovarian cortex, among which 22 patients (71%) had been exposed to chemotherapy before OTC. Recovery of ovarian function was considered total once menstruation occurred. Ovarian function recovery (OFR), ovarian graft survival, and incidence of pregnancy were related to previous chemotherapy exposure, type of chemotherapy and graft characteristics (number of grafted fragments and follicular density). MAIN RESULTS AND ROLE OF CHANCE: The amount of ovarian tissue collected was the only parameter to show any significant change between patients with versus without previous chemotherapy. At 1 year after OTT, the cumulative incidence of OFR was 83% (93% in patients exposed to chemotherapy and 67% in others (P = 0.14)). A low follicular density (<0.3 foll/mm2) in the transplant and a low number of grafted fragments (<16) were significantly associated with a delayed OFR. Graft survival at 2 years after OTT was 77%. It was significantly lower in patients exposed to bifunctional alkylating agents before ovarian cryopreservation and in patients with a low follicular density. The proportion of women who succeeded in having at least one live birth was 23% in the total population, 0% (0/9) in the group 'no previous chemotherapy', and 32% (7/22) in the group 'previous chemotherapy'. The cumulative incidence of pregnancy (Kaplan-Meier) at 3 years after OTT was 36% overall and 49% in case of previous chemotherapy, with no difference related to previous chemotherapy exposure. In total there were 13 pregnancies and 8 births in 7 patients. LIMITATIONS, REASONS FOR CAUTION: The pathology in the two groups of patients was not comparable. In the group of patients who had chemotherapy before OTC, there were 95% of hematological malignancies. In the group of patients who did not have chemotherapy before OTC only 1 out of 9 patients had a malignant hematological disease while 44% had some pathology affecting the ovaries. Few women are available for study and only large changes are likely to have statistical significance. WIDER IMPLICATIONS OF THE FINDINGS: These results suggest that prior cancer chemotherapy should no longer be considered a limitation to cryopreservation of ovarian tissue and current recommendations in this regard should be revised. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the Agence de la Biomédecine (France's biomedical office). There are no competing interests to report. TRIAL REGISTRATION NUMBER: NCT02184806.

New Insights on Diagnostic Reproducibility of Biphasic Mesotheliomas: A Multi-Institutional Evaluation by the International Mesothelioma Panel From the MESOPATH Reference Center.

INTRODUCTION: The 2015 WHO classification of tumors categorized malignant mesothelioma into epithelioid, biphasic (BMM), and sarcomatoid (SMM) for prognostic relevance and treatment decisions. The survival of BMM is suspected to correlate with the amount of the sarcomatoid component. The criteria for a sarcomatoid component and the interobserver variability between pathologists for identifying this component are not well described. In ambiguous cases, a "transitional" (TMM) subtype has been proposed but was not accepted as a specific subtype in the 2015 WHO classification. The aims of this study were to evaluate the interobserver agreement in the diagnosis of BMM, to determine the nature and the significance of TMM subtype, and to relate the percentage of sarcomatoid component with survival. The value of staining for BRCA-1-associated protein (BAP1) and CDKN2A(p16) fluorescence in situ hybridization (FISH) were also assessed with respect to each of the tumoral components. METHODS: The study was conducted by the International Mesothelioma Panel supported by the French National Cancer Institute, the network of rare cancer (EURACAN) and in collaboration with the International Association for the Study of Lung Cancer (IASLC). The patient cases include a random group of 42 surgical biopsy samples diagnosed as BMM with evaluation of SMM component by the French Panel of MESOPATH experts was selected from the total series of 971 BMM cases collected from 1998 to 2016. Fourteen international pathologists with expertise in mesothelioma reviewed digitally scanned slides (hematoxylin and eosin - stained and pan-cytokeratin) without knowledge of prior diagnosis or outcome. Cases with at least 7 of 14 pathologists recognizing TMM features were selected as a TMM group. Demographic, clinical, histopathologic, treatment, and follow-up data were retrieved from the MESOBANK database. BAP1 (clone C-4) loss and CDKN2A(p16) homozygous deletion (HD) were assessed by immunohistochemistry (IHC) and FISH, respectively. Kappa statistics were applied for interobserver agreement and multivariate analysis with Cox regression adjusted for age and gender was performed for survival analysis. RESULTS: The 14 panelists recorded a total of 544 diagnoses. The interobserver correlation was moderate (weighted Kappa = 0.45). Of the cases originally classified as BMM by MESOPATH, the reviewers agreed in 71% of cases (385 of 544 opinions), with cases classified as pure epithelioid in 17% (93 of 544), and pure sarcomatoid in 12% (66 of 544 opinions). Diagnosis of BMM was made on morphology or IHC alone in 23% of the cases and with additional assessment of IHC in 77% (402 of 544). The median overall survival (OS) of the 42 BMM cases was 8 months. The OS for BMM was significantly different from SMM and epithelioid malignant mesothelioma (p < 0.0001). In BMM, a sarcomatoid component of less than 80% correlated with a better survival (p = 0.02). There was a significant difference in survival between BMM with TMM showing a median survival at 6 months compared to 12 months for those without TMM (p < 0.0001). BAP1 loss was observed in 50% (21 of 42) of the total cases and in both components in 26%. We also compared the TMM group to that of more aggressive patterns of epithelioid subtypes of mesothelioma (solid and pleomorphic of our large MESOPATH cohort). The curve of transitional type was persistently close to the OS curve of the sarcomatoid component. The group of sarcomatoid, transitional, and pleomorphic mesothelioma were very close to each other. We then considered the contribution of BAP1 immunostaining and loss of CDKN2A(p16) by FISH. BAP1 loss was observed in 50% (21 of 41) of the total cases and in both component in 27% of the cases (11 of 41). There was no significant difference in BAP1 loss between the TMM and non-TMM groups. HD CDKN2A(p16) was detected in 74% of the total cases with no significant difference between the TMM and non-TMM groups. In multivariate analysis, TMM morphology was an indicator of poor prognosis with a hazard ratio = 3.2; 95% confidence interval: 1.6 - 8.0; and p = 0.003 even when compared to the presence of HD CDKN2A(p16) on sarcomatoid component (hazard ratio = 4.5; 95% confidence interval: 1.2 - 16.3, p = 0.02). CONCLUSIONS: The interobserver concordance among the international mesothelioma and French mesothelioma panel suggests clinical utility for an updated definition of biphasic mesothelioma that allows better stratification of patients into risk groups for treatment decisions, systemic anticancer therapy, or selection for surgery or palliation. We also have shown the usefulness of FISH detection of CDKN2A(p16) HD compared to BAP1 loss on the spindle cell component for the separation in ambiguous cases between benign florid stromal reaction from true sarcomatoid component of biphasic mesothelioma. Taken together our results further validate the concept of transitional pattern as a poor prognostic indicator.

Towards semantic-driven high-content image analysis: an operational instantiation for mitosis detection in digital histopathology.

This study concerns a novel symbolic cognitive vision framework emerged from the Cognitive Microscopy (MICO(1)) initiative. MICO aims at supporting the evolution towards digital pathology, by studying cognitive clinical-compliant protocols involving routine virtual microscopy. We instantiate this paradigm in the case of mitotic count as a component of breast cancer grading in histopathology. The key concept of our approach is the role of the semantics as driver of the whole slide image analysis protocol. All the decisions being taken into a semantic and formal world, MICO represents a knowledge-driven platform for digital histopathology. Therefore, the core of this initiative is the knowledge representation and the reasoning. Pathologists' knowledge and strategies are used to efficiently guide image analysis algorithms. In this sense, hard-coded knowledge, semantic and usability gaps are to be reduced by a leading, active role of reasoning and of semantic approaches. Integrating ontologies and reasoning in confluence with modular imaging algorithms, allows the emergence of new clinical-compliant protocols for digital pathology. This represents a promising way to solve decision reproducibility and traceability issues in digital histopathology, while increasing the flexibility of the platform and pathologists' acceptance, the one always having the legal responsibility in the diagnosis process. The proposed protocols open the way to increasingly reliable cancer assessment (i.e. multiple slides per sample analysis), quantifiable and traceable second opinion for cancer grading, and modern capabilities for cancer research support in histopathology (i.e. content and context-based indexing and retrieval). Last, but not least, the generic approach introduced here is applicable for number of additional challenges, related to molecular imaging and, in general, to high-content image exploration.

[The French mesothelioma network from 1998 to 2013]. / Mésothéliome: les dispositifs en place en France « le réseau mésothéliome ¼ 1998-2013.

Mesothelioma is a rare disease less than 0.3% of cancers in France, very aggressive and resistant to the majority of conventional therapies. Asbestos exposure is nearly the only recognized cause of mesothelioma in men observed in 80% of case. In 1990, the projections based on mortality predicted a raise of incidence in mesothelioma for the next three decades. Nowadays, the diagnosis of this cancer is based on pathology, but the histological presentation frequently heterogeneous, is responsible for numerous pitfalls and major problems of early detection toward effective therapy. Facing such a diagnostic, epidemiological and medico-legal context, a national and international multidisciplinary network has been progressively set up in order to answer to epidemiological survey, translational or academic research questions. Moreover, in response to the action of the French Cancer Program (action 23.1) a network of pathologists was organized for expert pathological second opinion using a standardized procedure of certification for mesothelioma diagnosis. We describe the network organization and show the results during this last 15years period of time from 1998-2013. These results show the major impact on patient's management, and confirm the interest of this second opinion to provide accuracy of epidemiological data, quality of medico-legal acknowledgement and accuracy of clinical diagnostic for the benefit of patients. We also show the impact of these collaborative efforts for creating a high quality clinicobiological, epidemiological and therapeutic data collection for improvement of the knowledge of this dramatic disease.

[Ameloblastoma of the jaws. A retrospective analysis from 1994 to 2007]. / Améloblastomes des mâchoires. Analyse rétrospective de 1994 à 2007.

INTRODUCTION: Ameloblastomas and keratocysts are the most frequent epithelial odontogenic tumors of the jaws. They have a high recurrence rate. This retrospective study reviews the features of ameloblastomas operated on in our unit from 1994 to 2007. PATIENTS AND METHODS: The studied parameters were sex, ethnic origin, age at diagnosis, clinical signs, radiographic presentation, site distribution, histological type, treatment, and follow-up records. RESULTS: One hundred and sixteen patients were included (with 239 surgical samples). The mean age was 36 years, with a majority of Europeans, 60% of multilocular radiolucent lesions with root resorption, mandibular location (93%). Twenty-one percent of the patients presented with an impacted tooth, the third molar in 79% of cases. Fifty percent of the lesions were from 5 to 13cm in length, 10% longer than 13cm. The most common histological type was follicular ameloblastoma. Patients were treated by enucleation in 82% of cases and radical mandibular resection with reconstruction in 11% of cases. The follow-up was documented for 96% of the patients with a 44% recurrence rate. Seventy-four percent of patients with a double recurrence presented with a "follicular" ameloblastoma. DISCUSSION: We prefer a well-performed enucleation which preserves surrounding bone. The high rate of follicular type recurrence should more systematically lead to a combined treatment: periostectomy and tooth extraction. Our data was compared with previously published large series.

Coexpression of biological key modulators in primary colorectal carcinomas and related metastatic sites: implications for treatment with cetuximab.

BACKGROUND: Recent studies suggested substantial differences between primary tumors and metastases for EGFR expression in colorectal cancer (CRC). The aim of the study was to correlate the expression of a panel of molecular markers between primary CRC samples and metastases. METHODS: Expressions of EGFR, pEGFR, VEGF, pVEGF, PTEN, pAKT and p21 were analyzed in 28 primary tumors and 32 liver metastases by immunohistochemistry performed on formalin-fixed, paraffin-embedded sections from 46 CRC patients. The molecular profiles were evaluated by tissue micro-array. The correlation between tumor and metastasis biomarker expressions was tested. RESULTS: Among 60 CRC samples, 25% were EGFR positive, 38% were pEGFR positive, 38% were VEGF positive, 48% were pVEGF positive, 70% were pAKT positive and 51% were p21 positive. PTEN was deleted in 39% of cases and absence of p21 expression was found in 49% of cases. A significant correlation was observed between primary tumors and metastases for pAKT (p = 0.037) and pEGFR (p = 0.0002) status. In patients treated with cetuximab-based therapy (n = 18), p21 appeared as a significant predictive factor of response (p = 0.036). CONCLUSION: Biomarkers status may change between primary and metastatic sites in CRC, with potential implications for the identification of patients who are likely to respond to anti-EGFR treatment.

[CT imaging features of bronchiolitis]. / Aspect TDM des bronchiolites.

Bronchiolitis may be encountered in numerous clinical circumstances. Previous history of smoking, infections, toxic exposure, immunodeficiency, chronic inflammatory disorders or transplantation must be known. CT findings consist in centrilobular micronodules with sharp or ill borders of various density and/or a mosaic attenuation with expiratory air trapping. Tree-in-bud pattern suggest an inflammatory or infectious bronchiolitis. The associated presence of bronchiectasis and bronchiolectasis must be considered. Imaging-pathologic correlations will be presented for inflammatory bronchiolitis (infectious bronchiolitis, hypersensitivity pneumonitis, respiratory bronchiolitis, follicular bronchiolitis, diffuse panbronchiolitis) and fibrosing bronchiolitis (constrictive bronchiolitis, post-infectious bronchiolitis, toxic fume exposure, transplant-related bronchiolitis).

[Epithelioid hemangioendothelioma mimicking hypersensitivity pneumonitis]. / Hémangioendothéliome épithélioïde pulmonaire mimant une pneumopathie d'hypersensibilité

Epithelioid haemangioendothelioma is a rare vascular tumour of slow growth and unfavourable outcome. The diagnosis of the pulmonary localisation is difficult and can mimic by clinical and radiological features other diagnosis as hypersensitivity pneumonitis. We report the case of a 28-year-old man, farmer handling with palm tree pollens, admitted to the hospital for dry cough. Clinical and thoracic computed tomography findings revealed diffuse infiltrating pneumopathy; bronchoalveolar lavage results and professional exposure were suggestive for hypersensivity pneumonitis. Surgical lung biopsy with immunochemistry study concluded to pulmonary epithelioid haemangioendothelioma. Extra pulmonary localisation research was negative. No treatment was indicated. At three years, the patient is steel asymptomatic. Epithelioid haemangioendothelioma is a tumour of intermediate malignancy, of which pulmonary localisation has a nonspecific clinical presentation mimicking diffuse infiltrating pneumonitis. Diagnosis is essentially made by surgical lung biopsy with pathological and immunohistochemical study.

Prognostic value of MET, RON and histoprognostic factors for urothelial carcinoma in the upper urinary tract.

PURPOSE: RON (recepteur d'origine Nantais) (Santa Cruz Technology, Santa Cruz, California) and c-met (Dako, Glostrup, Denmark) are members of the c-met proto-oncogene family. c-met encodes a receptor tyrosine kinase and has a role in oncogenesis. RON has a role in cell transformation and epithelial tumorigenesis. Over expression of the 2 genes has been demonstrated in human bladder cancer. We explored whether over expression of the 2 proteins has a role in the tumorigenesis and defined histoprognostic factors of poor clinical outcomes in patients with these tumors. MATERIALS AND METHODS: We reviewed the records of 42 patients with upper urinary tract urothelial carcinoma. A total of 24 tumors were localized in the renal pelvis and 18 were in the ureter. Immunohistochemical staining for RON and c-met was performed using tissue microarrays. RESULTS: Patient age was 46 to 100 years (mean 70.6). Of the patients 23 (54%) died of disease. Over expression of c-met was associated with a higher risk of embolism (p = 0.0002), while over expression of RON was not significantly associated with emboli (p = 0.5). Univariate analysis showed that relapse was significantly associated with ureteral localization (p = 0.02), vascular invasion (p = 0.003), and high grade (p = 0.04) and high stage (0.02) urothelial carcinoma. The association with vascular invasion, and high grade and high stage urothelial carcinoma was also statistically significant (p <0.0001). Notably superficial tumors showed an important relapse rate (p = 0.003). CONCLUSIONS: Independent prognostic factors of relapse in upper urinary tract urothelial carcinoma are ureteral localization, vascular invasion, high grade and high stage. c-met seems to influence the development of vascular invasion via an unknown mechanism. Nevertheless, to our knowledge an association between c-met over expression and aggressive clinical behavior in upper urinary tract carcinomas has not been previously reported.

Multidisciplinary interobserver agreement in the diagnosis of idiopathic pulmonary fibrosis.

The purpose of the present study was to evaluate the accuracy of the diagnosis of idiopathic pulmonary fibrosis (IPF) by respiratory physicians in six European countries, and to calculate the interobserver agreement between high-resolution computed tomography reviewers and histology reviewers in IPF diagnosis. The diagnosis of usual interstitial pneumonia (UIP) was assessed by a local investigator, following the American Thoracic Society/European Respiratory Society consensus statement, and confirmed when a minimum of two out of three expert reviewers from each expert panel agreed with the diagnosis. The level of agreement between readers within each expert panel was calculated by weighted kappa. The diagnosis of UIP was confirmed by the expert panels in 87.2% of cases. A total of 179 thoracic high-resolution computed tomography scans were independently reviewed, and an interobserver agreement of 0.40 was found. Open or thoracoscopic lung biopsy was performed in 97 patients, 82 of whom could be reviewed by the expert committee. The weighted kappa between histology readers was 0.30. It is concluded that, although the level of agreement between the readers within each panel was only fair to moderate, the overall accuracy of a clinical diagnosis of idiopathic pulmonary fibrosis in expert centres is good (87.2%).

[Pulmonary arterial hypertension due to tumor emboli]. / Hypertension artérielle pulmonaire postembolique tumorale.

INTRODUCTION: Pulmonary arterial hypertension (PAH) is rare in the presence of malignancy and tumour embolisation is one of several possible pathological mechanisms. CASE REPORTS: We report our experience of 5 clinical cases and undertake a literature revue of the pathophysiological mechanisms and of the possible diagnostic and therapeutic approaches. CONCLUSIONS: Neoplastic PAH due to tumour micro-emboli is rare and the diagnosis difficult to establish. Cytological examination of pulmonary arterial blood could allow early institution of appropriate chemotherapy and lead to an improvement in the grave prognosis of this condition.

Aurora-A/STK-15 is a predictive factor for recurrent behaviour in non-invasive bladder carcinoma: a study of 128 cases of non-invasive neoplasms.

Aurora-A, a member of serine/threonine kinase, is implied in mitosis and centrosome maturation. Increasing levels of Aurora-A have been shown to be present in several malignancies and especially in bladder cancer. No immunohistochemical marker has shown to be able to predict the clinical outcome of patients with superficial bladder cancer, except MIB-1, as a predictive marker of relapse and progression. The aim was to investigate the expression of Aurora-A and MIB-1 in tissue micro arrays of superficial bladder cancer representative of pTa papillary urothelial neoplasm with different degrees of aggressiveness (low malignant potential [PUNLMP], non-invasive papillary urothelial carcinoma low grade [NILGC], non-invasive papillary urothelial carcinoma high grade [NIHGC] and carcinoma in situ). We analysed predictive values of both markers, their specificity and sensitivity in tumor recurrence. Aurora-A was a sensitive marker to predict tumor recurrence especially for pTa (PUNLMP, NILGC; PUNLMP p<0.001, NILGC p<0.001) with statistical significant correlation between immunohistochemical staining and clinical outcome. MIB-1 expression displayed statistical difference p=0.002 in the PUNLMP group and p=0.03 in the NILGC group. Aurora-A is a more sensitive marker than MIB-1 to predict relapse in pTa bladder neoplasias. The combination of both markers seems to have a very powerful predictive value of recurrence (p<0.001).

[Update on the pathomorphological assessment of vasculopathies in pulmonary arterial hypertension]. / Vaskulopathien bei pulmonal-arterieller Hypertonie Update zur pathomorphologischen Beurteilung.

Pulmonary arterial hypertension (PAH) is a term which has recently been redefined and includes idiopathic pulmonary arterial hypertension, familial pulmonary arterial hypertension PAH related to specific pathological conditions (e.g. connective tissue diseases), as well as PAH caused by veno-occlusive disease or capillary hemangiomatosis. The clinical manifestation seems to be related to a peculiar pathological anatomy involving small, muscular pulmonary arteries, capillaries and veins. In addition to common hypertrophy of the tunica media, other vascular compartments may also be affected by intimal thickening or adventitial fibrosis. Moreover, complex lesions, such as so called plexiform lesions and arteritis can be present in certain forms of the disease. While the recent identification of responsible gene mutations in subgroups of patients have shed some light on disease evolution, therapeutic strategies must currently rely on vasodilative and antimitogenic drugs acting on the intimal and medial level of the affected pulmonary vessels. The clinical outcome of patients suffering from PAH remains poor, underlining our need for a better comprehension of disease pathophysiology, and thus for the characterization of specific histomorphological patterns.

Occult alveolar haemorrhage in pulmonary veno-occlusive disease.

Pulmonary veno-occlusive disease (PVOD) is a rare cause of pulmonary arterial hypertension that affects predominantly post-capillary pulmonary vessels. A major concern with PVOD is the poor response to available therapies and the risk of pulmonary oedema with continuous intravenous epoprostenol. The present authors hypothesised that alveolar haemorrhage may be a characteristic feature of pulmonary veno-occlusive disease, as compared with other forms of pulmonary arterial hypertension that predominantly involve pre-capillary pulmonary arteries. This paper reports a series of 19 patients with either PVOD (n = 8) or idiopathic pulmonary arterial hypertension (IPAH; n = 11) who underwent bronchoalveolar lavage. Cytological analyses were performed and differential counts were made on Perls-stained preparations. The Golde score was used to assess alveolar haemorrhage. As compared with IPAH, PVOD was characterised by a higher percentage of haemosiderin-laden macrophages (40+/-37 versus 3+/-6%), resulting in elevated Golde scores (81+/-88 versus 4+/-10). It was concluded that occult alveolar haemorrhage is a common feature of pulmonary veno-occlusive disease. Detecting occult alveolar haemorrhage may be of interest in the diagnostic approach of pulmonary veno-occlusive disease.

Segmental pulmonary veno-occlusive disease secondary to lung cancer.

This report describes two cases of segmental pulmonary vein occlusion secondary to lung malignancy in which lung biopsies showed histological features of veno-occlusive disease. These are the first cases to be reported in the literature in which such lung parenchymal histological changes are described in association with lung malignancy.

[Diffuse idiopathic interstitial pneumonias. International multidisciplinary consensus classification by the American Thoracic Society and the European Respiratory Society, principal clinico-pathological entities, and diagnosis]. / Pneumopathies interstitielles diffuses idiopathiques. Classification de Consensus International Multidisciplinaire de l'American Thoracic Society et de l'European Respiratory Society, principales entités anatomo-cliniques, et conduite du diagnostic.

INTRODUCTION: The classification of the idiopathic interstitial pneumonias includes seven clinico-pathologic entities. The diagnosis is based on a multidisciplinary approach, integrating the clinical evaluation, the high-resolution computerised tomography, and the pathological pattern. STATE OF THE ART: A definitive diagnosis of idiopathic pulmonary fibrosis relies on the association of a suggestive clinico-radiological profile and a pathological pattern of usual interstitial pneumonia. Nonspecific interstitial pneumonia is a recently described clinico-pathologic entity, with a better prognosis than that of idiopathic pulmonary fibrosis. Cryptogenic organising pneumonia has been included in the group of idiopathic interstitial pneumonias because of its idiopathic and multifocal characteristics, although it does not predominate in the lung interstitium. Desquamative interstitial pneumonia and respiratory bronchiolitis with interstitial lung disease are rare entities with predominance in young smoking adults. Lymphoid interstitial pneumonia, usually encountered in the context of Sjögren's syndrome, is very rare in its idiopathic form. Acute interstitial pneumonia is responsible for idiopathic acute respiratory distress syndrome. PERSPECTIVES: The current classification of idiopathic interstitial pneumonias better defines the diagnostic criterias of each clinico-pathologic entity, and is expected to facilitate clinical research. CONCLUSIONS: This classification has clinical implications, with prognostic and therapeutic significance.

[Pulmonary hypertension: CT findings in pulmonary veno-occlusive disease]. / Hypertension pulmonaire: aspect tomodensitométrique de la maladie veino-occlusive.

PURPOSE: To describe the CT findings of pulmonary veno-occlusive disease. MATERIALS AND METHODS: Pre-therapeutic CT of 15 patients suffering from pulmonary veno-occlusive disease were retrospectively reviewed. Pathologic evaluation of pulmonary veno-occlusive disease was obtained after post mortem examination or pulmonary transplantation. CT protocol always included intravenous helical CT and high resolution CT. RESULTS: The most frequent CT-findings in pulmonary veno-occlusive disease were the following: ground glass opacity with poorly defined nodular opacities (73%), septal lines (93%), and adenopathy (80%). Pericardial (60%) and pleural effusions (27%) were also noted. Other parenchymal findings were unusual. CONCLUSION: HRCT must be systematically included in the initial CT evaluation of pulmonary hypertension. Combination of poorly defined nodular opacities, septal lines, and adenopathy are indicative of pulmonary veno-occlusive disease.

Pulmonary veno-occlusive disease after neoadjuvant mitomycin chemotherapy and surgery for lung carcinoma.

Pulmonary veno-occlusive disease (PVOD), an uncommon cause of pulmonary hypertension (PH) has been reported following treatment of a variety of different malignancies with various chemotherapy. We report here the cases of two patients with non-small cell lung cancer (NSCLC) who developed fatal PH after combined treatment with surgery and a mitomycin containing perioperative chemotherapy (PCT). PVOD was documented at autopsy in one patient and was strongly suspected in the other patient who had an identical clinical presentation and in whom the work-up looking for another cause of PH was negative. Mitomycin was incriminated in both cases. Without questioning the potential interest of perioperative chemotherapy in resectable NSCLC, these observations illustrate the risks related to the combination of pneumotoxic chemotherapy and thoracic surgery.

Excessive alcohol consumption favours high risk polyp or colorectal cancer occurrence among patients with adenomas: a case control study.

BACKGROUND AND AIMS: Excessive alcohol consumption is a risk factor for developing colorectal adenomas. This study aimed to investigate the influence of excessive alcohol consumption on the occurrence of high risk polyps (adenoma > or = 10 mm, villous component, high grade dysplasia) or colorectal cancer among patients with at least one colonic adenoma. PATIENTS AND METHODS: Three groups of patients with at least one colorectal adenoma were included in a case control study: 401 heavy drinkers (group HD, mean daily alcohol intake 117 (SD 4) g/day for a mean duration of 22 (SD 0.6) years), aged 57 (0.5) years (78% men); 152 patients suffering from irritable bowel syndrome (IBS), aged 61 (0.9) years (57% male); and 108 patients with a family history (FH) of colorectal adenoma or cancer, aged 55 (1) years (64% male). Exclusion criteria were: anaemia, haematochezia, personal history of colorectal adenoma or cancer, and for groups HD and IBS a family history of colorectal adenoma and/or cancer. Relative risks were estimated by the odds ratio (OR) using a logistic regression model and were expressed with 95% confidence interval (CI). RESULTS: After age and sex adjustment, the likelihood of having an adenoma > or = 10 mm was higher in group HD than in the IBS group (OR 1.8, 95% CI (1.2-2.7)) and the likelihood of having high risk adenomas or cancer was higher in group HD compared with the IBS group (OR 1.6, 95% CI (1.2-2.1)) and the FH group although this was not significant (OR 1.6, 95% CI (0.97-2.6) (p=0.081); 90% CI (1.03-2.4)). After age and sex adjustment, the likelihood of having an adenoma with high grade dysplasia or cancer was higher in group HD than in the IBS group (OR 1.7, 95% CI (1.02-2.8)) or group FH, although this was not significant (OR 3.7, 95% CI (0.98-15) (p=0.076); 90% CI (1.10-12.47)). CONCLUSION: In patients with at least one colorectal adenoma, excessive alcohol consumption increases the likelihood of developing high risk adenomas or colorectal cancer.