Laurence Choudat

Deficient mismatch repair phenotype is a prognostic factor for colorectal cancer in elderly patients

OBJECTIVE About 15% of colorectal adenocarcinomas have a deficient DNA mismatch repair phenotype. The frequency of deficient DNA mismatch repair tumours increases with age due to the hypermethylation of hMLH1 promoter. The study aimed to determine the prognostic value of deficient DNA mismatch repair phenotype in elderly patients. DESIGN Mismatch repair phenotype was retrospectively determined by molecular analysis in consecutive resected colorectal adenocarcinoma specimens from patients over 75 years of age from 4 Oncology centres. RESULTS 231 patients (median age: 81, range: 75-100) were enrolled from 2005 to 2008. Mean prevalence of deficient DNA mismatch repair phenotype was 22.5%, and 36% for patients over 85 years. Deficient DNA mismatch repair status was significantly associated with older age, female sex, proximal colon primary and high grade tumour. For stage II tumours no deficient DNA mismatch repair tumours had a recurrence at end of follow-up compared to 17% for tumours with proficient phenotype. The proficient phenotype status was significantly associated with worse age-adjusted overall survival [HR 2.60; 95% CI 1.05-6.44; p=0.039]. For stage III tumours a trend for less recurrence was observed for deficient DNA mismatch repair phenotype (16%) compared to proficient phenotype (36%). CONCLUSION deficient DNA mismatch repair phenotype is a prognostic factor in stage II colorectal tumour in elderly patients. Our results suggest that mismatch repair phenotype should be taken in consideration for adjuvant chemotherapy decision in elderly patients.

The Learning Curve of Transrectal Ultrasound-guided Prostate Biopsies: Implications for Training Programs

OBJECTIVE To assess the quality of specimens obtained from prostate biopsies performed by urology residents and evaluate the number of procedures required to perform high-quality transrectal ultrasound (TRUS)-guided prostate biopsies. MATERIALS AND METHODS Between 2006 and 2009, 770 patients underwent TRUS-guided prostate biopsies in our academic center. During the 6 semesters of this period, 24 residents (4 per semester) performed 1 session of 5.6±1.5 procedures each month for a total of 33.6±9 procedures during the study. The first session was performed with a senior urologist. Prostate cancer detection rate and standards of quality (average length of prostatic core biopsy specimens and absence of prostatic tissue) were retrospectively studied between the beginning and the end of each semester. RESULTS A total of 12,760 biopsy cores were performed for 770 procedures. Mean patient age (64.5±6.1 years), and median prostate-specific antigen (8.7±3.7 ng/mL) were comparable between the study periods. The average length of biopsy cores significantly improved (+10%) from the first (12±2.7 mm) to the last month (13.2±2.1 mm) with a plateau after 12 procedures. Overall, cancer detection rate was 47% and was stable during the semester (41.3% the first month vs 44.1% the last month; P=.39). On univariate and multivariate analysis the mean length of biopsy specimens was associated with the number of procedures (P<.001) and the number of cores performed (P<.001). CONCLUSION Twelve procedures are necessary to perform high-quality TRUS-guided prostate biopsies without compromising prostate cancer detection. In current training programs, we strongly recommend that residents have direct supervision for a minimum of 12 cases before they are allowed to perform TRUS-guided biopsies with indirect supervision.

Liver Involvement in Patients With PiZZ‐Emphysema, Candidates for Lung Transplantation

Information about the prevalence and nature of liver disorders in adults with alpha1‐antitrypsin deficiency is scarce. At our center, systematic liver biopsy screening is part of the evaluation before lung transplantation (LT) in the emphysema patients with the PiZZ phenotype. Our aim was to report our experience with this prospective screening. Clinical, liver function, and imaging parameters as well as liver histology data were analyzed for 23 consecutive adult patients with PiZZ severe emphysema referred to our center for consideration of LT from 2006 to 2014. Overall 20 (87%) featured chronic liver disease characterized by a chronic inflammation and/or a significant portal fibrosis on histology. Two of the 23 patients (8.7%) had septal fibrosis according to the Metavir and Ishak scores and met our definition of severe chronic liver disease. They were both clinically asymptomatic with normal liver function tests. On abdominal ultrasonography, the liver appeared normal in one patient and with abnormal contours in the other. Our data indicate that in adults with PiZZ‐related emphysema being evaluated for LT, most patients had some histologic involvement. The prevalence of severe liver dysfunction is <10%.

A case report of reninoma: radiological and pathological features of the tumour and characterization of tumour-derived juxtaglomerular cells in culture.

Case report: A 20-year-old woman presented with malignant hypertension associated with hypokalemia, metabolic alkalosis and elevated plasma renin and aldosterone levels. Computed tomography angiography (CTA) evidenced a 22 mm tissular mass in the posterior cortex of the left kidney, and 18F-flurodeoxyglucose PET (18-FDG PET) imaging showed no hypermetabolism of the tumour. Following nephron-sparing surgery, blood pressure and potassium levels rapidly normalized, allowing interruption of all treatments within 2 weeks. Discussion: Reninoma is a rare juxtaglomerular cell tumour (JGCT) producing excessive amounts of renin resulting in severe hypertension. Pathological studies revealed that tumoural cells highly expressed renin and contained electron-dense structures, typical of renin-containing granules. Tumoural cells also exhibited the vascular cell surface marker CD34, but, in contrast with previous reports, did not express the tyrosine-protein kinase Kit (cKit or CD117). Dissociation of the tumour allowed to obtain confluent cultures of elongated smooth muscle actin (SMA)-positive cells producing high amounts of renin. However, after the first passage, subcultured human juxtaglomerular cells rapidly lost renin and CD34 expressions and their ability to produce renin. Conclusion: The present case of reninoma emphasizes the need for CTA in the etiologic work up of otherwise unexplained severe hypertension. 18-FDG PET imaging showed no hypermetabolism of the tumour, in accordance with its reported benignity. Pathological studies further emphasized that high expressions of renin and CD34 are typical hallmarks of reninoma. Although CD117 has been proposed to represent a reliable marker of JGCT, the present findings indicate that reninomas may not always express this marker.

P.04 - Modification par la mise en place d’une Réunion de concertation pluridisciplinaire de la prise en charge des patients âgés de 75 ans et plus opérés d’un adénocarcinome colique de stade II ou III

Introduction La prise en charge des cancers du colon des patients âges est caracterisee par une proportion importante d’abstention therapeutique. Nous avons recherche si la mise en place de la reunion de concertation pluridisciplinaire (RCP) a modifie les pratiques. Patients et Methodes Nous avons compare la prise en charge de tous les patients consecutifs âges de 75 ans et plus, opere d’un adenocarcinome colique entre 1995 et 2000 avant la mise en place de la RCP (periode 1) et entre 2001 et 2005 apres la mise en place de la RCP (periode 2). La selection des patients a ete realisee par la revue du fichier du service d’anatomopathologie confronte au bilan d’extension realise pour chaque patient opere. Resultats Quatre vingt seize patients de 75 ans et plus ont eu une resection d’un adenocarcinome colique pendant la periode 1 et 104 pendant la periode 2. Parmi ceux-ci, il y avait 40 cancers de stade II et 23 de stade III pendant la periode 1 (âge median : 80, extremes : 75 - 94), 44 de stade II et 29 de stade III pendant la periode 2 (âge median : 82 ans, extremes : 75 - 95). Pendant la periode 2 : 64 % des dossiers ont ete discute en RCP en peri-operatoire (54 % des dossiers de stade II et 79 % des dossiers de stade III). Le taux de presentation des dossiers en RCP a significativement augmente avec le temps (55 % de Janvier 2001 a Mai 2003 vs 79 % de Juin 2003 a Decembre 2005, p = 0,05). La proportion de chimiotherapie adjuvante apres resection d’un cancer de stade II pendant la periode 1 et la periode 2 etait de 5 % et 7 % et pour les stades III de 26 % et de 41 % respectivement (p = 0,3). Pendant la periode 2 la proportion de decision de chimiotherapie dans les stade III etait de 52 % en cas de soumission du dossier a la RCP et de 0 % en l’absence de discussion pluridisciplinaire. Pour les stade III, 40 % des patients de 75-79 ans ont ete traites par chimiotherapie adjuvante vs 15 % des patients âges de 80 ans et plus (p = 0,03). Une evolution de la prescription de chimiotherapie etait constate selon la periode : pendant la periode 1, 6/ 9 patients âges 75 a 79 ans et 0/14 patients âges de 80 ans et plus, ont recu une chimiotherapie adjuvante. Pendant la periode 2, 6/9 patients âges de 75 a 79 ans et 6/20 des patients âges de 80 ans et plus, ont recu une chimiotherapie adjuvante, mais aucun apres 85 ans. Conclusion L’instauration d’une RCP a permis de poser un plus grand nombre d’indication de chimiotherapie adjuvante. La proportion de patients âges discutee en RCP augmente avec le temps. Le grand âge reste neanmoins associe a une non-prescription de chimiotherapie adjuvante. Le benefice d’une chimiotherapie adjuvante chez des patients âges de plus de 80 ans reste a etablir. L’etablissement de criteres de selection des patients âges devant beneficier d’une chimiotherapie adjuvante est souhaitable.

Xanthomatous Posttraumatic Fibro-Osseous Lesion of the Rib: A Rare and Underrecognized Entity. Case Report and Literature Review

Posttraumatic fibro-osseous lesion (PTFOL) is a rare lesion that typically affects the ribs and is probably a posttraumatic reactive process. Because PTFOL is often misdiagnosed as fibrous dysplasia, osteoid osteoma, benign fibrous histiocytoma or rib metastases, chest wall resection, leading to a significant morbidity, is the main treatment modality. We report the case of a 30-year-old male patient with no history of previous trauma presenting with chest pain. Computed tomography scan showed an eighth left rib well-defined ovoid and hypodense lesion with circumferential sclerotic margin and no cortical breakthrough. Posterolateral thoracotomy was performed and a histological diagnosis of xanthomatous posttraumatic fibro-osseous lesion of the rib was made. PTFOL is a benign lesion that should be recognized to avoid unnecessary surgical treatment and complications. We provide a summary of clinical, histopathological, and radiological aspects of PTFOL and discuss differential diagnoses.

Fusionsbiopsie der Prostata liefert zuverlässige Ergebnisse

Die transrektale Sonografie mit systematischer Biopsie gilt derzeit als Standard fur die Diagnose eines Prostatakarzinoms. Allerdings ist das Verfahren nicht immer prazise – hochgradige Erkrankungen konnen ubersehen und niedrig maligne Veranderungen ubertherapiert werden. Die Fusionsbiopsie konnte eine Alternative darstellen, aber dazu muss sie zuverlassig reproduzierbar sein. Das haben Mediziner aus den USA gepruft.

P.09 Les adénocarcinomes colorectaux présentent une fréquence très élevée d’instabilité des microsatellites après l’âge de 75 ans

Introduction Environ 15 % des adenocarcinomes colorectaux presentent une instabilite des microsatellites (IMS). Ces tumeurs ont un meilleur pronostic que celles sans IMS. La frequence des tumeurs avec IMS augmente avec l’âge par un mecanisme d’hypermethylation du promoteur du gene hMLH1. Cependant, la prevalence exacte de l’IMS et ses potentielles implications cliniques ne sont pas connues apres l’âge de 75 ans. Patients et Methodes Tous les patients consecutifs ayant une determination du statut IMS ont ete inclus dans deux centres entre 2005 et 2008. La determination du statut IMS a ete realisee par l’analyse de 5 marqueurs quasi-monomorphes (BAT26, BAT25, NR21, NR22, NR24). L’instabilite d’au moins 3 marqueurs etant requise pour porter le diagnostic d’IMS. La prevalence de l’IMS a ete comparee entre les patients de moins de 75 ans et de 75 ans et plus. Les patients presentant un syndrome HNPCC avec mutation identifiee ont ete exclus de l’etude. Resultats 754 patients ont ete inclus dont 272 (36 %) patients âges de 75 ans ou plus (âge median 82 ans, extremes 75 a 101 ans). Il y avait 425 hommes et 329 femmes. La proportion de femmes etait de 38 % avant 75 ans et de 53 % a partir de 75 ans (p 0,9). Parmi les 21 patients dont les tumeurs presentaient une IMS et pour lesquels des resultats d’immunomarquage hMLH1 et hMSH2 etaient disponibles, il y avait une extinction de l’expression d’hMLH1 et de hMSH2 chez 8/10 et 1/10 des patients de 75 ans et plus et chez 6/11 et 1/11 des patients de moins de 75 ans. Conclusion La prevalence de l’IMS dans les adenocarcinomes colorectaux est significativement plus elevee apres l’âge de 75 ans. Dans cette tranche d’âge, l’IMS est significativement plus frequente chez les femmes. Cette variation ne semble pas liee a une hypermethylation differente du promoteur de hMLH1. La valeur pronostique de l’IMS dans cette tranche d’âge est en cours d’evaluation.