[Optical coherence tomography of bladder resection specimen]. / Tomographie par densité optique des pièces de résection des tumeurs de vessie.

INTRODUCTION: The diagnosis of bladder urothelial tumors is based on bladder resection and histological analysis of the specimen. The time to obtain the results of the histological analysis increases the treatment delay. Furthermore, the lack of muscle on the specimen forces the surgeon to practice on other procedure. Full field optical coherence tomography (FFOCT) is a recent imaging technique to analyze tissue. The aim of our study was to evaluate the feasibility and diagnostic accuracy of FFOCT to detect muscle and tumor in bladder resection specimen. PATIENTS AND METHODS: We analyzed with the FFOCT technique bladder resection specimen of 24 consecutives patients. Three readers did the blind analyze of the images, looking for the presence of muscle and tumor on each specimen. Their results were compared with histological analysis to calculate diagnostic accuracy for each reader. RESULTS: Mean sensibilities for the detection of muscle and tumor were respectively 75% and 81%. Mean specificities for the detection of muscle and tumor were respectively 78.3% and 55.3%. CONCLUSIONS: Our results suggest that the FFOCT is feasible to analyze bladder resection specimen. Sensibilities and specificities calculated are encouraging for the detection of muscle and tumor. The accuracy of this detection and early-staging tool should be validated by larger studies. LEVEL OF EVIDENCE: 3.

Self-assembling peptide matrix for the prevention of esophageal stricture after endoscopic resection: a randomized controlled trial in a porcine model.

Esophageal stricture formation after extensive endoscopic resection remains a major limitation of endoscopic therapy for early esophageal neoplasia. This study assessed a recently developed self-assembling peptide (SAP) matrix as a wound dressing after endoscopic resection for the prevention of esophageal stricture. Ten pigs were randomly assigned to the SAP or the control group after undergoing a 5-cm-long circumferential endoscopic submucosal dissection of the lower esophagus. Esophageal diameter on endoscopy and esophagogram, weight variation, and histological measurements of fibrosis, granulation tissue, and neoepithelium were assessed in each animal. The rate of esophageal stricture at day 14 was 40% in the SAP-treated group versus 100% in the control group (P = 0.2). Median interquartile range (IQR) esophageal diameter at day 14 was 8 mm (2.5-9) in the SAP-treated group versus 4 mm (3-4) in the control group (P = 0.13). The median (IQR) stricture indexes on esophagograms at day 14 were 0.32 (0.14-0.48) and 0.26 (0.14-0.33) in the SAP-treated and control groups, respectively (P = 0.42). Median (IQR) weight variation during the study was +0.2 (-7.4; +1.8) and -3.8 (-5.4; +0.6) in the SAP-treated and control groups, respectively (P = 0.9). Fibrosis, granulation tissue, and neoepithelium were not significantly different between the groups. The application of SAP matrix on esophageal wounds after a circumferential endoscopic submucosal dissection delayed the onset of esophageal stricture in a porcine model.

[Pathological findings of visible and non-visible tumors on multiparametric magnetic resonance imaging (MRI) prior to radical prostatectomy]. / Caractéristiques anatomopathologiques des tumeurs apparentes et non apparentes en IRM multiparamétrique de la prostate avant prostatectomie totale.

INTRODUCTION: As urologists are questioned about the overtreatment of localized prostate cancer, multiparametric MRI can diagnose significant prostate cancer thanks to targeted biopsies. However, some tumors cannot be detected by MRI. What are the pathological characteristics of those tumors? MATERIALS AND METHODS: We have selected 144 consecutive patients treated with radical prostatectomy for clinically localized prostate cancer diagnosed on systematic and targeted biopsies (Koelis®) according to multiparametric MRI findings. On MRI, each suspicious area was graded according to the PI-RADS score v1.0. On radical prostatectomy specimen, tumor foci with a Gleason score greater than 3+3 and/or a tumor volume greater than 0,5cm3 were considered significant. The grade-four tumoral volume was calculated by multiplying the tumoral volume by grade 4 tumoral percentage. RESULTS: Two hundred and seventy seven tumors were identified. A hundred and thirty nine were non-visible on MRI. They had a significantly lower volume (0.15cm3 versus 1.45cm3, P<0.0001) and a Gleason score significantly lower (P<0.0001) than apparent tumors. 17.3% of non-apparent tumors were significant. Moreover, the grade-four tumoral volume of significant non-apparent tumors was significantly lower than that of significant apparent tumors (0.11cm3 versus 0.66cm3, P<0.0001). CONCLUSION: Non-apparent prostate tumors on multiparametric MRI have a Gleason score, a tumor volume - and consequently - a grade 4 tumor volume significantly lower than apparent tumors. LEVEL OF PROOF: 4.

Topical hemostatic powder promotes reepithelialization and reduces scar formation after extensive esophageal mucosal resection.

The development of techniques for endoscopic resection has provided new strategies for radical conservative treatment of superficial esophageal neoplasms, even those that are circumferential, such as Barrett's neoplasia. However, it is necessary to prevent the formation of scar tissue that can be responsible for esophageal strictures following circumferential resection. Preliminary data have suggested the possible efficacy of a hemostatic powder in the promotion of wound healing. The study aims to assess the effectiveness of Hemospray (Cook Medical) in a swine model of post-endoscopic esophageal stricture. Our prospective controlled study included 21 pigs. A 6-cm circumferential submucosal dissection of the esophagus (CESD) was performed in each pig. Group 1 (n = 11) only underwent CESD and Group 2 (n = 10) had repeated Hemospray applications after CESD. Clinical, endoscopic, and radiological monitoring were performed, blood levels of four inflammatory or pro-fibrotic cytokines were assessed, and histological analysis was performed. Median esophageal diameter was greater in the group treated with Hemospray (2 mm [1-3] vs. 3 mm [2-4], P = 0.01), and the rate of symptomatic esophageal stricture was 100% and 60% in Groups 1 and 2, respectively (P = 0.09). The thicknesses of esophageal fibrosis and inflammatory cell infiltrate were significantly lower in Group 2 than in Group 1 (P = 0.002 and 0.0003, respectively). The length of the neoepithelium was greater in Group 2 than in Group 1 (P = 0.0004). Transforming growth factor-ß levels were significantly lower in Group 2 than in Group 1 (P = 0.01). The application of Hemospray after esophageal CESD reduces scar tissue formation and promotes reepithelialization, and therefore is a promising therapeutic approach in the prevention of post-endoscopic esophageal stricture.

[Full field optical coherence tomography of prostate biopsies: a step towards pre-histological diagnosis?]. / Tomographie par cohérence optique plein champ des biopsies de la prostate: un pas vers le diagnostic pré-histologique?

OBJECTIVES: To evaluate the value of full field optical coherence tomography (FFOCT) for cancer detection on prostate biopsies PATIENTS AND METHODS: Eight consecutive patients who underwent prostate biopsies for an elevated PSA or suspicious DRE findings were included in the study. For each patient, one to three biopsy cores were imaged with FFOCT immediately after sampling. Images obtained were analyzed by a pathologist blinded to the pathological results, and classified into three categories: non-cancerous tissue, suspicion of malignancy and prostate carcinoma. A pathological correlation analysis was further performed. RESULTS: Sixteen biopsy cores were analyzed. The median FFOCT procedure time was of 4 (3-5) minutes. No artifact was noted in subsequent pathological analysis. Six cores were involved with cancer and eight cores showed no evidence of cancer. On two cores, diagnosis was uncertain, and immuno-histochemical analysis confirmed cancer involvement in one of them. The agreement rate between standard histological analysis and FFOCT evaluation was of 81% (13/16). The three cases of disagreement were due to one false positive and two false negatives of FFOCT analysis. CONCLUSIONS: FFOCT of prostate biopsy cores seemed to be feasible and to allow concordant results with those of pathological analysis in the majority of the cases.

Value of multiparametric MRI in the work-up of prostate cancer.

The role of magnetic resonance imaging (MRI) in prostate cancer evaluation is controversial and likely underestimated. Technological advances over the past 5 years have demonstrated that multiparametric MRI, including diffusion-weighted imaging (DWI) and dynamic contrast-enhanced MRI, can evaluate the actual tumor burden of a newly diagnosed prostate cancer more accurately than sextant biopsy protocols. Tumor risk, defined by the D'Amico criteria, hence can be re-evaluated by multiparametric MRI. As a result, there is increasing evidence that MRI before repeat or even initial biopsy can accurately select patients who require immediate biopsies and those in whom biopsy could be deferred. Also, a relationship between apparent diffusion coefficient (ADC), calculated from DWI, and Gleason score was found. Thus, MRI before biopsy helps to detect high-grade tumors to target biopsies within areas of low ADC values. To achieve good targeting accuracy, transrectal ultrasound (TRUS)-MRI image registration is necessary. Three-dimensional deformable registration is sufficiently accurate to match TRUS and MRI volumes with a topographic precision of 1 mm. Real-time MRI-guided biopsy is another technique under evaluation. Both approaches will allow for increasing acceptance of focal therapies, should these techniques be validated in the future.

[pT3N0 prostate cancer treated with radical prostatectomy as sole treatment: Oncological results and predictive factors of recurrence]. / Cancer de la prostate de stade pT3N0 traité par prostatectomie radicale en monothérapie : résultats carcinologiques et facteurs prédictifs de récidive.

OBJECTIVES: To evaluate biological free survival in patients with locally advanced prostate cancer treated with radical prostatectomy (RP) as sole treatment, and to analyse predictive factors of recurrence. PATIENTS AND METHOD: We retrospectively studied patients treated between 1996 and 2006 for a pT3N0 prostate cancer with RP without any adjuvant treatment. The main endpoint was PSA relapse, defined as two successive elevations of PSA>0.2 ng/mL. An association between PSA free survival and PSA, Gleason score, pathological stage and surgical margins status was statistically assessed. RESULTS: A total of 147 patients were included. Median preoperative PSA was of 10 ng/mL. Pathological stage was pT3b in 30% of the cases and surgical margins showed cancer involvement in 63% of the cases. Gleason score was ≥3+4 in 74% of the cases. Postoperative PSA was undetectable in 121 (82%) patients. Median follow up following RP was of 5 years. The 5-year-PSA free survival was of 48%. Multivariate analysis showed that preoperative and postoperative PSA, as well as Gleason score were predictors of PSA relapse (P<0.05). In patients with undetectable postoperative PSA, 5-year-PSA free survival was of 56%. Seminal vesicle involvement and Gleason score ≥3+4 were the only independent predictors of PSA relapse. CONCLUSIONS: After RP for pT3N0 prostate cancer, the only predictive factors of recurrence were postoperative PSA and Gleason score. In case of undetectable postoperative PSA, surveillance seems acceptable if Gleason score is <3+4 and in the absence of seminal vesicle involvement.

[Prebiopsy multiparametric MRI of the prostate: the end of randomized biopsies?]. / IRM mutiparamétrique de la prostate avant biopsies : la fin des biopsies systématisées ?

OBJECTIVE: To evaluate the value of multiparametric MRI-targeted prostate biopsies in patients with suspected low-risk prostate cancer. PATIENTS AND METHOD: Patients with normal digital rectal examination and a PSA level between 4 and 10 ng/mL were prospectively included. A multiparametric MRI of the prostate was performed prospectively before the biopsies. 12-core randomized biopsies were performed, with additional targeted samples in each suspicious area identified on MRI. Detected cancers and their histological characteristics were compared between those two biopsy protocols. A micro focal cancer (MFC) was defined by the presence of less than 4mm of Gleason score 3+3 cancer on a single core. RESULTS: Seventy-one consecutive patients were included. The overall detection rate was of 53% (38/71). It was of 70% (26/37) in the presence of suspicious area on MRI versus 35% (12/34) in the absence of any suspicious area (P=0.004). MRI-targeted biopsies alone detected three cancers, none of which was a MFC. 12-core biopsies alone detected 14 cancers, including ten MFC (71%). In 21 patients, prostate cancer was detected by both the MRI-targeted and 12-core biopsies. The Gleason score in the MRI-targeted area was the highest Gleason score in 90% of the cases. It was high (>6) in 76% (16/21) of the patients. CONCLUSIONS: MRI-targeted biopsies detected less micro focal cancers than randomized 12-core biopsies. They did not seem however to decrease the detection of clinically significant cancers.

[Diffusion-weighted MR imaging of the prostate]. / IRM de diffusion de la prostate.

Functional imaging complements T2-weighted imaging in the evaluation of the prostate. The most frequently used techniques are diffusion-weighted imaging and perfusion imaging following the intravenous administration of contrast material. Perfusion imaging has high sensitivity and moderate specificity, even when using a quantitative technique, because contrast kinetics in some cases of peripheral zone prostatitis and benign transition zone hyperplasia may simulate cancer. Diffusion-weighted imaging is currently under evaluation but appears to be preferable to dynamic perfusion MR imaging because of its higher specificity and simpler acquisition. Functional imaging of the prostate is performed to detect cancers missed on biopsies or evaluate the volume of a newly diagnosed clinically localized cancer to assist in therapy selection. Future applications for image-guidance of targeted therapies to the tumor are currently investigational.

[Quantitative dynamic MRI and localisation of non-palpable prostate cancer]. / IRM dynamique quantitative et localisation du cancer de prostate non palpable.

PURPOSE: To determine whether quantitative dynamic contrast-enhanced MRI improves the performance of T2W-MRI for the localisation of non-palpable prostate cancer (PCa) and for the estimation of tumor volume. MATERIALS AND METHODS: Twenty-three patients (PSA: 8.91+/-6.2ng/m) with a non-palpable cancer underwent endorectal MRI with T2W and dynamic contrast enhanced (DCE) imaging before radical prostatectomy. Each level of evaluation (apex, mid-portion, base) was divided in eight areas (24 areas per prostate and 552 areas for the 23 patients). Localisation and volume of tumor foci greater than 0,2cc present on the radical prostatectmoy specimens were retrospectively correlated to their MR appearance on the 552 evaluated areas. The dynamic parameters included capillary permeability (K(trans)), maximum concentration of gadolinium after 60s of perfusion ([Gd]) and wash-out (K(ep)). Uni- and multivariate analysis were performed to determine which parameters were predictive of PCa. RESULTS: Mean values of K(trans), K(ep) and [Gd] were significantly higher in the 58 tumor foci greater than 0,2 cm(3) of the PZ and the TZ (all p<0.05). Logistic regression for each zone provides provided a value of the area under the ROC curve of 0.83 for the PZ and 0.81 for the TZ (0.7 and 0.75, respectively, for the T2W imaging), only significant for the PZ (p<0.002). Sensitivity and specificity were 79 and 77% for the PZ, 62.5 and 94% for the TZ. Above 0,2 cm(3), tumor volume on dynamic MR showed a mean difference of 51+/-100% (range: -145 to +248%). CONCLUSIONS: Quantitative dynamic MRI is more accurate than T2W imaging for tumor localisation of non-palpable cancer greater than 0,2 cm(3), but the difference is only significant for the PZ. Above this volume, correlation between tumor volume measured on dynamic MRI and that on the specimen is poor.

[Nontumoral epileptogenic lesions]. / Les lésions épileptogènes non tumorales.

Nontumoral epileptogenic lesions account for the major pathological group of surgical specimens obtained from patients with temporal or extratemporal drug-resistant epilepsy. Hippocampal sclerosis remains the predominant etiology, but cerebral cortical dysplasias actually make up the second major cause of nontumoral epilepsy and are increasingly recognized. The percentage of vascular lesions or glial/glio-mesodermal scars remains stable, but the minor or nonspecific lesion group is decreasing because of imaging investigation technique improvement.

[Late onset Rasmussen's syndrome: clinical and therapeutic characteristics]. / Le syndrome de Rasmussen à début tardif: caractéristiques cliniques et thérapeutiques.

Rasmussen's syndrome is a rare inflammatory brain disease characterized by severe intractable epilepsy, and unilateral progressive motor defect associated with controlateral hemispheric atrophy. The disorder usually affects children, although occasional reports of adult-onset Rasmussen's syndrome have been reported. We report her four patients in whom seizures began in adolescence or adulthood with clinical and radiological symptoms suggesting the diagnosis of Rasmussen's syndrome. We compared them with thirty-three cases described in the literature between 1987 and 2004. While adult-onset Rasmussen's syndrome may mimic the early-onset form, symptoms often progress more slowly and the neurological defect is more variable. Occipital lobe involvement appears to be more common than in the childhood form, and some atypical features may be noted such as bilateral hemispheric involvement or a picture of temporal lobe epilepsy or the présence of movement disorders at the beginning of the disease. Surgical hemispheric disconnection that appears the most effective treatment in children to improve seizure control is not indicated in adults for evident functional reasons. Based on recent pathogenic concepts, different medical treatments may be proposed. Large multicentric controlled studies are mandatory to define a clear medical therapeutic strategy in these cases of adult-onset.

Anti-colony-stimulating factor-1 antibody staining in primary breast adenocarcinomas correlates with marked inflammatory cell infiltrates and prognosis.

BACKGROUND: Clinical studies have shown that a marked lymphoplasmocytic reaction in breast tumors is associated with poor prognosis. Such findings raise the possibility that an inflammatory cell reaction might be a tumor-induced response that tends to promote tumor growth. PURPOSE: We assessed the expression of colony-stimulating factor-1 (CSF-1) as well as the prevalence of specific tumor-infiltrating lymphocytes and monocytes in breast tumors. METHODS: Tissue sections were obtained from archival paraffin blocks from 196 breast cancer patients. Seventy-eight percent of the women had been treated by mastectomy and 22% by lumpectomy. Median age of the patients was 54 years, and median follow-up was 7.3 years. Immunohistochemical and in situ hybridization techniques were used to characterize the specimens. RESULTS: Markedly high numbers of CD45RO-positive T- and L26-positive B-cell infiltrates were found in 13% and 17% of the tissue specimens, respectively. CSF-1 receptor-positive monocytes were detected in 48% and CD68-positive monocytes in 90% of the tumors. In turn, tumors with large fractions of CD68-positive monocytes also showed CSF-1 receptor-positive monocytes (P < .0001). CSF-1 was expressed significantly in 74% of the tumors and the CSF-1 receptor in more than 50% of the tumors. Tumors with high percentages of CSF-1 expressing cells also had marked monocyte infiltrates (P = .035). The presence of marked CD45RO-positive T-cell infiltrates and apparent nuclear staining of CSF-1 in tumor cells were associated with the more frequent occurrence of metastases (P = .02 and P = .04, respectively) and with poor survival (P = .02 and P = .03, respectively). CONCLUSIONS: Large numbers of CD45RO-positive (activated memory but noncytotoxic) T cells as well as a predominant nuclear staining pattern for CSF-1 are associated with a poor outcome in breast cancer patients. IMPLICATIONS: Nuclear retention of CSF-1 could reflect CSF-1 turnover and function in tumor cells, but new approaches are needed to establish the significance of these observations. Secreted CSF-1 appears to cause monocyte recruitment and activation, thereby modulating immune functions and potentially the expression of the CD45RO phenotype in T cells.

Functional endothelin ET B receptors are selectively expressed in human oligodendrogliomas.

Endothelin-1 (ET-1), a vasoactive and mitogenic peptide mainly produced by vascular endothelial cells, may be involved in the progression of several human tumors. Here, we present an immunohistochemical analysis of the expression pattern of ET-1 receptor subtypes (ET(A)-R and ET(B)-R) and a functional study of their potential role in human oligodendrogliomas and oligoastrocytomas. By comparison, we assessed the corresponding expression patterns of glioblastomas. Interestingly, a nuclear localization of ET-1 receptor subtypes (associated or not with a cytoplasmic labeling) was constantly observed in tumor cells from all three glioma types. Moreover, we noted a distinct receptor distribution in the different gliomas: a nuclear expression of ET(B)-R by tumor cells was found to be restricted to oligodendrogliomas and oligoastrocytomas, while a nuclear expression of ET(A)-R was only detected in tumor cells from some glioblastomas. Using primary cultures of oligodendroglial tumor cells, we confirmed the selective expression of nuclear ET(B)-R, together with a plasma membrane expression, and further demonstrated that this receptor was functionally coupled to intracellular signaling pathways known to be involved in cell survival and/or proliferation: extracellular signal-regulated kinase and focal adhesion kinase activation, actin cytoskeleton reorganization. In addition, impairment of ET(B)-R activation in these cells by in vitro treatment with an ET(B)-R-specific antagonist induced cell death. These data point to ET-1 as a possible survival factor for oligodendrogliomas via ET(B)-R activation and suggest that ET(B)-R-specific antagonists might constitute a potential therapeutic alternative for oligodendrogliomas.

[Cerebral cavernomas, epilepsy and seizures. Natural history and therapeutic strategy]. / Cavernomes intracrâniens, épilepsie et crises d'épilepsie. Histoire naturelle et modalités thérapeutiques.

PURPOSE: To review, from a retrospective series of 48 patients presenting with seizures associated with one or more supratentorial cavernoma(s), the natural history of the seizures and outcome according to medical and surgical treatment. METHODS: Patients were divided into two groups: group A included patients presenting with a single seizure or rare seizures (n=21), and group B patients having intractable epilepsy (n=27). All received antiepileptic drugs and 35 were operated on (12 in the group A and 23 in the group B). Stereo-EEG was performed in 8 patients in group B. Surgery included lesionectomy alone (n=16), resection of the cavernoma and perilesional tissue (n=7) or tailored corticectomy including the cavernoma (n=12). RESULTS: The natural history of seizures was different in the two groups: mean age at seizure onset was 25 years in group B and 33 years in group A (p<0.05), seizures were partial in all patients in group B and 8 patients in group A (p<0.05). Seizure frequency and periodicity also varied. Prolonged seizure-free periods were observed. The cavernoma was temporal in 17 patients in group B and 4 patients in group A (p<0.01). In group A, seizure outcome was favorable following surgery or with antiepileptic medication only (7 patients out of 12 operated were seizure-free, as were 5 out of 7 non-operated). In group B, seizure outcome was better after surgery than with medication only (17 patients out of 23 operated were in Engel's Class I, while 3 patients of 4 non-operated patients had persisting seizures despite antiepileptic polytherapy). CONCLUSION: Variations in seizure severity in patients harboring cavernomas suggest different therapeutic approaches. In case of unique or rare seizures, surgical resection of the cavernoma is appropriate, but benefits of surgery over antiepileptic medication in terms of seizure control remains unclear. Intractable epilepsy associated with cavernomas is better controlled after surgery rather than with medication only. In these patients, a detailed preoperative work-up is necessary and should be followed by wide resection associated or not with corticectomy, especially in the temporal lobe. Evaluation of outcome after surgery should consider the surgical strategy, antiepileptic medications and the patient's seizure history.

[Criteria of diagnosis and grading of oligodendrogliomas or oligo-astrocytomas according to the WHO and Sainte-Anne classifications]. / Oligodendrogliomes et oligo-astrocytomes critères diagnostiques et grading de malignité selon l'OMS et l'hôpital Sainte-Anne.

Two main classification systems are used in France for the histological typing and grading of oligodendrogliomas: the WHO and Sainte-Anne Hospital (SA) classifications. According to the WHO, the typing of diffuse gliomas is based on the predominant cell type, oligodendroglial versus astrocytic. In contrast, the SA classification is based on the distinction of two patterns of tumor growth, solid tumor tissue versus isolated tumor cells and also relies on imaging and clinical features. According to this approach, the SA classification includes in the category of oligodendrogliomas, the fibrillary or gemistocytic diffuse astrocytomas (WHO grade II) as well as a substantial proportion of astrocytomas WHO grade III, 2) the WHO uses multiple histological criteria for the grading of oligodendrogliomas (grade II versus grade III), including the degree of differentiation, cellular atypia, mitotic activity and necrosis. In contrast, the SA grading of these tumors (grade A versus B) only uses two criteria: the presence or absence of endothelial hyperplasia, and the presence or absence of contrast enhancement. This last criterion allows overcoming the problems related to the representativeness of surgical samples. Difficulties and discrepancies regarding the diagnosis of oligodendrogliomas are in part due to the lack of immunomarker for the identification of tumoral oligodendrocytes. The potential interest of new markers of oligodendroglial precursors for the diagnosis of these tumors will further be discussed.