Networking for ovarian rare tumors: a significant breakthrough improving disease management.

BACKGROUND: Rare ovarian tumors represent >20% of all ovarian cancers. Given the rarity of these tumors, natural history, prognostic factors are not clearly identified. The extreme variability of patients (age, histological subtypes, stage) induces multiple and complex therapeutic strategies. METHODS: Since 2011, a national network with a dedicated system for referral, up to 22 regional and three national reference centers (RC) has been supported by the French National Cancer Institute (INCa). The network aims to prospectively monitor the management of rare ovarian tumors and provide an equal access to medical expertise and innovative treatments to all French patients through a dedicated website, www.ovaire-rare.org. RESULTS: Over a 5-year activity, 4612 patients have been included. Patients' inclusions increased from 553 in 2011 to 1202 in 2015. Expert pathology review and patients' files discussion in dedicated multidisciplinary tumor boards increased from 166 cases in 2011 (25%) to 538 (45%) in 2015. Pathology review consistently modified the medical strategy in 5-9% every year. The rate of patients' files discussed in RC similarly increased from 294 (53%) to 789 (66%). An increasing number (357 in 5 years) of gynecologic (non-ovarian) rare tumors were also registered by physicians seeking for pathological or medical advice from expert tumor boards. CONCLUSION: Such a nation-wide organization for rare gynecological tumors has invaluable benefits, not only for patients, but also for epidemiological, clinical and biological research.

Decline in territory size and fecundity as a response to carrying capacity in an endangered songbird.

Density-dependent processes are fundamental mechanisms for the regulation of populations. Ecological theories differ in their predictions on whether increasing population density leads to individual adjustments of survival and reproductive output or to dominance and monopolization of resources. Here, we use a natural experiment to examine which factors limit population growth in the only remaining population of the endangered pale-headed brush finch (Atlapetes pallidiceps). For three distinct phases (a phase of population suppression, 2001-2002; expansion due to conservation management, 2003-2008; and equilibrium phase, 2009-2014), we estimated demographic parameters with an integrated population model using population size, the proportion of successfully breeding pairs and their productivity, territory size, and mark-recapture data of adult birds. A low proportion of successful breeders due to brood parasitism (0.42, 95% credible interval 0.26-0.59) limited population growth before 2003; subsequent culling of the brood parasite resulted in a two-fold increase of the proportion of successful breeders during the 'expansion phase'. When the population approached the carrying capacity of its habitat, territory size declined by more than 50% and fecundity declined from 1.9 (1.54-2.27) to 1.3 (1.12-1.53) chicks per breeding pair, but the proportion of successful breeders remained constant (expansion phase: 0.85; 0.76-0.93; equilibrium phase: 0.86; 0.79-0.92). This study demonstrates that limiting resources can lead to individual adjustments instead of despotic behavior, and the individual reduction of reproductive output at high population densities is consistent with the slow life-history of many tropical species.

Update on gene fusions and the emerging clinicopathological landscape of peritoneal and pleural mesotheliomas and other neoplasms.

BACKGROUND: Mesothelioma is a rare and aggressive malignant neoplasm arising from mesothelial cells, which occasionally manifests recurrent fusions. EWSR1/FUS-CREB, YY1, MAP3K8, NR4A3, and ALK-rearranged proliferations have been reported in limited series with no clear histological or clinical correlations, limiting clinicians' ability to assess prognosis and integrate these new entities into therapeutic decisions. The aim of this study was to better characterize these rearranged proliferations histologically, molecularly, and clinically. METHODS: Clinical, pathological, and comprehensive transcriptome and mutation data were collected for each case. RESULTS: A total of 41 tumors were included, encompassing 7 ALK, 10 MAP3K8, 4 NR4A3, 8 ESWR1/FUS::ATF1, 8 EWSR1::YY1, and 4 SUFU-fused cases. We found a female predominance, except for cases harboring NR4A3 and SUFU; and most patients were around 60 years of age, but those harboring ALK or EWSR1/FUS::ATF1 gene fusions were younger. Each group exhibited distinct histological, immunohistochemical, molecular features, and oncological courses. Specifically, MAP3K8 and ALK presented PAX8+ papillary proliferations, ESWR1/FUS::ATF1 and EWSR1::YY1 displayed angiomatoid fibrous histiocytoma-like patterns, while SUFU showcased 'tissue culture'-like spindle cell proliferation. Poor prognosis factors were the pleural site, male sex, Ki67 ≥10%, and ESWR1/FUS::ATF1 or SUFU gene fusions. CONCLUSIONS: This study significantly broadens the spectrum of mesothelial tumors associated with fusions, offering insight into novel epithelioid (mesothelial) proliferations with distinctive histological appearances, molecular profiles, and prognoses to guide adapted treatments for patients.

Accuracy of intraoperative pathological examination of SLN in cervical cancer.

OBJECTIVE: Early cervical cancer patients with pelvic lymph node metastasis do not benefit from radical hysterectomy. Assessment of the SLN status is thus crucial before deciding to perform a radical hysterectomy as opposed to aortic dissection only followed by definitive radiation therapy. Accuracy of frozen section of SLN has been questioned and deserves further investigation. METHODS: Stage IA-IB1 cervical cancer patients who underwent SLN then full pelvic dissection at the Claudius Regaud Cancer Center in Toulouse, France, were included. RESULTS: At least one SLN was identified in all 94 patients. Bilateral detection rate was 80.8%. Ectopic drainage area was found in 19 patients (20.2%). Sentinel lymph node involvement was found in 11 patients (11.7%). Sensitivity and NPV of frozen section pathological examination for the detection of macrometastatic disease was 100%, sensitivity for the detection of macro and micrometastatic disease, excluding ITC, was 88.9%, and NPV was 98.8%. Micrometastasis and isolated tumor cells (ITC) undetected at frozen section examination were found in 1 patient (1.06%) and 2 lymph nodes (1.24%), and in 2 patients (2.13%) and 2 lymph nodes (1.24%), respectively. Final pathology sensitivity of SLN was 100% for both macro and micrometastatic disease, including ITC. CONCLUSION: In our institution, intraoperative frozen examination of SLN accurately predicts the status of pelvic lymph nodes and is effective for selecting intraoperatively the group of patients who benefit from radical hysterectomy. In addition, our results suggest that patients with small tumors and bilateral detection of SLN can be spared full pelvic lymphadenectomy.

Prognostic significance of low volume sentinel lymph node disease in early-stage cervical cancer.

OBJECTIVE: Evaluate prognostic significance of low volume disease detected in sentinel nodes (SN) of patients with early stages cervical cancer. Although pathologic ultrastaging of SN allows for identification of low volume disease, including micro-metastasis and isolated tumor cells (ITC), in up to 15% of cases, prognostic significance of these findings is unknown. METHODS: A total of 645 records from 8 centers were retrospectively reviewed. Enrolled in our study were patients with early-stage cervical cancer who had undergone surgical treatment including SN biopsy followed by pelvic lymphadenectomy and pathologic ultrastaging of SN. RESULTS: Macrometastasis, micrometastasis, and ITC were detected by SN ultrastaging in 14.7%, 10.1%, and 4.5% patients respectively. False negativity of SN ultrastaging reached 2.8%. The presence of ITC was not associated with significant risk, both for recurrence free survival and overall survival. Overall survival was significantly reduced in patients with macrometastasis and micrometastasis; hazard ratio for overall survival reached 6.85 (95% CI, 2.59-18.05) and 6.86 (95% CI, 2.09-22.61) respectively. Presence of micrometastasis was an independent prognostic factor for overall survival in a multivariable model. CONCLUSION: Presence of micrometastasis in SN in patients with early stage cervical cancer was associated with significant reduction of overall survival, which was equivalent to patients with macrometastasis. No prognostic significance was found for ITC. These data highlight the importance of SN biopsy and pathologic ultrastaging for the management of cervical cancer.

Celiac lymph node resection and porta hepatis disease resection in advanced or recurrent epithelial ovarian, fallopian tube, and primary peritoneal cancer.

INTRODUCTION: Prognostic value of complete macroscopic resection of primary disease has been reported and confirmed in several publications. Published data indicate that extensive upper abdominal disease involving the hepatic pedicle and celiac trunk is associated with an abortion of the surgical procedure or with suboptimal residual disease. METHODS: All patients who had disease at the porta hepatis or celiac lymph node resection as part of cytoreductive surgery were included. Medical and operative records with particular emphasis on extent and distribution of disease spread, number of peritonectomy procedures, visceral resections, and lymphadenectomy procedures were examined. RESULTS: A total of 28 patients who underwent some kind of celiac lymph node resection or resection of metastatic involvement of the porta hepatis were included. Median preoperative serum Ca-125 level was 78U/ml (range, 30-2950U/ml), and median ascites volume was 1900ml (range, 0-10,000ml). Of the 28 patients, 23 underwent supra-radical surgery for diffuse peritoneal carcinomatosis. Median operative time was 252minutes (range, 100-540minutes). Complete cytoreduction to CCO was achieved in all except one case, who was cytoreduced to millimetric residue. Fifteen patients had positive celiac nodes and nineteen patients had peritoneal disease in the porta hepatis region. DISCUSSION: Resection of enlarged nodes and metastatic disease to the porta hepatis is feasible with an acceptable morbidity. The decision to undergo an aggressive cytoreductive surgery is based on appropriate patient selection depending on the extension of surgical procedure, on medical comorbidities, and on the potential to tolerate an extensive procedure, rather than on specific anatomic locations.

Laparoscopic pelvic exenteration for gynaecological malignancy: is there any advantage?

INTRODUCTION: Pelvic exenteration (PE) remains one of the most mutilating surgical procedures with important postoperative morbidity. Laparoscopic approach has emerged in an attempt to reduce postoperative complications. The aim of the present study was to compare outcomes between laparoscopic pelvic exenteration combined with a vaginal or perineal approach, versus classical approach. METHODS: A cohort study was performed by identifying patients who underwent laparoscopic pelvic exenteration, and retrospectively comparing data with open cases from the same period of time, from 2000 to 2008. RESULTS: Fourteen patients underwent laparoscopic PE and 29 patients underwent an open exenterative procedure. All patients except one (97.6%) had received prior radiotherapy. Eighteen patients (41.9%) underwent total PE, 17 anterior PE (39.5%), and 8 posterior PE (18.6%). Urinary diversion (UD) technique consisted of 24 Miami pouch (68.6%), 9 Bricker diversion (25.7%), 1 Kock pouch (2.9%), and 1 ureterostomy (2.9%). Most frequent postoperative complications were related to the urinary diversion (45%) and bowel reconstruction (27.9%). Median estimated blood loss for the laparoscopy and laparotomy group was 400 ml (range 200-700 ml) and 875 ml (range 200-1600 ml), respectively. Transfusion rate was also significantly higher in the laparotomy group. Operative time, margin status, length of hospital stay, operative and postoperative morbidity, and disease and overall survival were not significantly different between both groups. CONCLUSIONS: Laparoscopic PE is feasible with curative intent to selected patients. Potential postoperative advantages of laparoscopic approach when compared to classical approach, oncological safety of the procedure, and QOL considerations need to be further investigated.

Incidence of micrometastases in histologically negative para-aortic lymph nodes in advanced cervical cancer patients.

OBJECTIVE: Aims of the study were to identify the incidence of micrometastases in negative para-aortic lymph nodes, and to assess the utility of ultrastaging in histologic evaluation of para-aortic lymph nodes. MATERIAL AND METHODS: Patients with advanced cervical cancer and negative para-aortic lymph nodes after routine histology examination were included. Paraffin-embedded tissue blocks were cut into 5-µm-thick slides at step serial sections at 200-µm intervals until there was no lymph node tissue left. 7 to 14 slides were obtained per lymph node and an immunohistochemistry staining with anti-cytokeratin antibody (EA1/EA3) was performed. RESULTS: 581 histologically negative aortic nodes of 24 patients with advanced cervical cancer were assessed for para-aortic micrometastases (PAM). The incidence of micrometastases by the total number of studied lymph nodes was 0.003%. PAM were identified in 2 patients (8.3%), and additional submicrometastases were also found in one of them (4.1%). A single metastatic cluster of less than 0.2 mm was found in an afferent lymphatic vessel of another patient, not considered as a submicrometastases. PAM incidence was too low to allow for evaluation of associated risk factors, and for analysis of prognostic significance. CONCLUSION: Although examination of PAM with ultrastaging and IHC is expensive and time-consuming, and difficult to be routinely applied to all negative lymph nodes retrieved in a para-aortic lymphadenectomy, this study adds to current evidence that removal of aortic nodes may benefit a subgroup of advanced cervical cancer patients with PAM and negative aortic lymph node at imaging techniques including PET-scan.

Hybrid imaging by SPECT/CT for sentinel lymph node detection in patients with cancer of the uterine cervix.

INTRODUCTION: Conventional lymphoscintigraphy provides planar images with little spatial information on location of pelvic sentinel lymph nodes (SLN). SPECT has better spatial resolution and, in combination with anatomic accuracy provided by CT improves SLN preoperative localization. The aim of the study was to report on the results of hybrid imaging of SLN in early cervical cancer patients treated at Claudius Regaud Cancer Center. METHODS: Stages IA-IB1 cervical cancer patients undergoing preoperative SPECT/CT for SLN detection were analysed. RESULTS: Forty-one patients were included. A 100% SLN detection rate was achieved when a combined technique (radiotracer and blue dye) was used. At least one SLN was clearly visualized by SPECT/CT in 39 of 41 patients (95%) and full anatomic concordance with intraoperative anatomical location of SLN was found in 37 of the 39 patients with at least one SLN identified by SPECT/CT (95%). Location of removed SLN included the external and internal iliac area in 88% patients, the common iliac area in 10.5%, and the inframesenteric para-aortic area in 1.5%. No SLN was found in the infrarenal para-aortic region. Lymph node involvement was identified in 5 patients (12.1%). SLN correctly predicted lymph node involvement in all node-positive patients. However, SPECT/CT failed to identify 1 of the 5 metastatic SLN. DISCUSSION: SPECT/CT accurately detected preoperative SLN topography and enhanced diagnostic sensitivity of SLN imaging, improving surgical approach to patients with cervical cancer staging. Diagnostic quality of anatomic landmarks of CT images of SPECT/CT could be further improved by the use of contrast injected CT.

Breast-conserving surgery with or without radiotherapy vs mastectomy for ductal carcinoma in situ: French Survey experience.

From March 2003 to April 2004, 77 physicians throughout France prospectively recruited 1289 ductal carcinoma in situ (DCIS) patients and collected data on diagnosis, patient and tumour characteristics, and treatments. Median age was 56 years (range, 30-84). Ductal carcinoma in situ was diagnosed by mammography in 87.6% of patients. Mastectomy, conservative surgery alone (CS) and CS with radiotherapy (CS+RT) were performed in 30.5, 7.8 and 61.7% of patients, respectively. Thus, 89% of patients treated by CS received adjuvant RT. Sentinel node biopsy (SNB) and axillary dissection (AD) were performed in 21.3 and 10.4% of patients, respectively. Hormone therapy was administered to 13.4% of the patients (80% tamoxifen). Median tumour size was 14.5 mm (6, 11 and 35 mm for CS, CS+RT and mastectomy, respectively, P<0.0001). Nuclear grade was high in 21% of patients, intermediate in 38.5% and low in 40.5%. Excision was considered complete in 92% (CS) and 88.3% (CS+RT) of patients. Oestrogen receptors were positive in 69.8% of assessed cases (31%). Treatment modalities varied widely according to region: mastectomy rate, 20-37%; adjuvant RT, 84-96%; hormone treatment, 6-34%. Our survey on current DCIS management in France has highlighted correlations between pathological features (tumour size, margin and grade) and treatment options, with several similar variations to those observed in recent UK and US studies.

Paratubal endometrioid cystadenocarcinoma: case report and review.

BACKGROUND: Paratubal masses are common, but paratubal carcinoma is an extremely rare entity. CASE: We report a case of a 44-year-old nulliparous female who suffered from abdominal pain for three months. Abdominal and pelvic ultrasound revealed a 30 cm left adnexal mass originally. Laparotomy with bilateral salpingo-oophorectomy was performed. Final pathology indicated a heterogeneous tumor with benign, borderline, and endometrioid carcinoma areas. A repeat surgery was decided in order to complete hysterectomy, omentectomy, pelvic and paraaortic lymphadenectomy. Surgical staging did not reveal residual disease at pathological examination. After 36 months of follow-up, no recurrence has occurred. CONCLUSION: To our knowledge, no case of paratubal invasive endometrioid adenocarcinoma has previously been described. This case has been managed according to the recommendations of ovarian cancer, which seems to be an acceptable option.

[Primary management of endometrial carcinoma. Joint recommendations of the French society of gynecologic oncology (SFOG) and of the French college of obstetricians and gynecologists (CNGOF)]. / Prise en charge primaire des cancers de l'endomètre : recommandations SFOG-CNGOF.

OBJECTIVES: The management of endometrial carcinoma is constantly evolving. The SFOG and the CNGOF decided to jointly update the previous French recommendations (Institut national du cancer 2011) and to adapt to the French practice the 2015 recommendations elaborated at the time of joint European consensus conference with the participation of the three concerned European societies (ESGO, ESTRO, ESMO). MATERIAL AND METHODS: A strict methodology was used. A steering committee was put together. A systematic review of the literature since 2011 has been carried out. A first draft of the recommendations has been elaborated, with emphasis on high level of evidence. An external review by users representing all the concerned discipines and all kinds of practice was completed. Three hundred and four comments were sent by 54 reviewers. RESULTS: The management of endometrial carcinoma requires a precise preoperative workup. A provisional estimate of the final stage is provided. This estimation impact the level of surgical staging. Surgery should use a minimal invasive approach. The final pathology is the key of the decision concerning adjuvant therapy, which involves surveillance, radiation therapy, brachytherapy, or chemotherapy. CONCLUSION: The management algorithms allow a fast, state of the art based, answer to the clinical questions raised by the management of endometrial cancer. They must be used only in the setting of a multidisciplinary team at all stages of the management.

Immunohistochemical evaluation of two antibodies against PD-L1 and prognostic significance of PD-L1 expression in epithelioid peritoneal malignant mesothelioma: A RENAPE study.

BACKGROUND: Epithelioid peritoneal malignant mesothelioma (EPMM) is the most common subtype of this aggressive tumor. We compared two antibodies against PD-L1, a recent theranostic biomarker, and evaluated the prognostic value of PD-L1 expression by mesothelial and immune cells in EPMM. METHODS: Immunohistochemistry was performed on 45 EPMM. Clinical and pathological data were extracted from the RENAPE database. Using E1L3N and SP142 clones, inter-observer agreement, PD-L1 expression by mesothelial and immune cells and inter-antibody agreement were evaluated. The prognostic relevance of PD-L1 expression was evaluated in 39 EPMM by univariate and multivariate analysis of overall survival (OS) and progression-free survival (PFS). RESULTS: Inter-observer agreement on E1L3N immunostaining was moderate for mesothelial and immune cells, and fair for mesothelial and poor for immune cells using SP142. Using E1L3N, 31.1% of mesothelial and 15.6% of immune cells expressed PD-L1, and 22.2% of mesothelial and 26.7% of immune cells using SP142. Inter-antibody agreement was moderate. In most positive cases, 1-5% of tumor cells were positive. Using E1L3N, PD-L1 expression by lymphocytes was associated with better OS and PFS by both univariate and multivariate analysis. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy predicted better prognosis than other treatments. Solid subtype was an independent prognostic factor for worse OS. CONCLUSION: E1L3N appeared easier to use than SP142 to evaluate PD-L1 expression. A minority of EPMM expressed PD-L1, and only a few cells were positive. PD-L1 expression by immune cells evaluated with E1L3N was an independent prognostic factor in EPMM.

Diffuse malignant peritoneal mesothelioma: Evaluation of systemic chemotherapy with comprehensive treatment through the RENAPE Database: Multi-Institutional Retrospective Study.

PURPOSE: Diffuse malignant peritoneal mesothelioma (DMPM) is a severe disease with mainly locoregional evolution. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is the reported treatment with the longest survival. The aim of this study was to evaluate the impact of perioperative systemic chemotherapy strategies on survival and postoperative outcomes in patients with DMPM treated with curative intent with CRS-HIPEC, using a multi-institutional database: the French RENAPE network. PATIENTS AND METHODS: From 1991 to 2014, 126 DMPM patients underwent CRS-HIPEC at 20 tertiary centres. The population was divided into four groups according to perioperative treatment: only neoadjuvant chemotherapy (NA), only adjuvant chemotherapy (ADJ), perioperative chemotherapy (PO) and no chemotherapy before or after CRS-HIPEC (NoC). RESULTS: All groups (NA: n = 42; ADJ: n = 16; PO: n = 16; NoC: n = 48) were comparable regarding clinicopathological data and main DMPM prognostic factors. After a median follow-up of 61 months, the 5-year overall survival (OS) was 40%, 67%, 62% and 56% in NA, ADJ, PO and NoC groups, respectively (P = 0.049). Major complications occurred for 41%, 45%, 35% and 41% of patients from NA, ADJ, PO and NoC groups, respectively (P = 0.299). In multivariate analysis, NA was independently associated with worse OS (hazard ratio, 2.30; 95% confidence interval, 1.07-4.94; P = 0.033). CONCLUSION: This retrospective study suggests that adjuvant chemotherapy may delay recurrence and improve survival and that NA may impact negatively the survival for patients with DMPM who underwent CRS-HIPEC with curative intent. Upfront CRS and HIPEC should be considered when achievable, waiting for stronger level of scientific evidence.

[Early epithelial lesions in prophylactic annexectomies in patients at high risk of ovarian cancer: Report of a series of 93 cases]. / Lésions épithéliales précoces dans les annexectomies prophylactiques chez des patientes à haut risque de cancer de l'ovaire : à propos d'une série de 93 cas.

OBJECTIVE: Tubal lesions detected in specimen of risk reducing salpingo oophorectomy (RRSO) for mutation BRCA1/2 seems to play a role in ovarian carcinogenesis. The main objective of this study is to evaluate the prevalence of occult neoplasia, of Serous Tubal Intraepithelial Carcinoma (STIC), and signature P53 in a cohort of patients who underwent a risk reducing salpingo oophorectomy. METHODS: From January 2010 to January 2014 unicentric, retrospective study on a consecutive cases cohort of RRSO for patients with a high risk of ovarian neoplasia (mutation BRCA 1/2 or family history). Pathological specimen should be analysed according to the SEE-FIM protocol. RESULTS: Ninety-three RRSO were recorded. Among them, 44% of the patients had the germ line mutation BRCA1, 30.1% BRAC2 and 18.2% had no identified mutation. In all, 33.3% of the RRSO reveal a signature P53, in the fimbria for 93.9%, 7.9% of them were bilateral. 1,1‰ (n=1) of the patients presented a unilateral STIC. We obtained 4.3% of occult neplasia: 3 ovarian high-grade serous carcinomas and 1 tubal high-grade serous carcinoma. Only the tubal carcinoma coexists with STIC. CONCLUSION: 5,4% of the patients who underwent RRSO had a diagnostic of occult neoplasia. One percent of the patients had an isolated STIC. These results agree with recent data of the literature. Extensive examination of the Fallopian tube opens up a new way to understand ovarian carcinogenesis.

[Breast ductal carcinoma in situ with microinvasion: pathological review and clinical implications]. / Carcinome canalaire in situ avec micro-invasion : spécificités anatomopathologiques et implications cliniques.

PURPOSE: Recent improvements in the detection of breast cancer at an early stage have resulted in a rising incidence of breast ductal carcinoma in situ with microinvasion. So far, there is no consensus regarding its optimal management. We hereby report on our 10-year single institutional experience in breast ductal carcinoma in situ with microinvasion including pathological reviewing. PATIENTS AND METHODS: All consecutive patients treated for a ductal carcinoma in situ with microinvasion at the Institut Claudius-Regaud (Toulouse, France) over a 10-year period were included in this study. We reviewed all available histological materials. RESULTS: Sixty-three patients were eligible for this study. Two patients presented with a lymph node invasion at diagnosis. Each patient benefited from initial surgical management, which consisted either in mastectomy (n=25) or conservative resection (n=37). Axillary exploration was performed in 52 patients (82%). After a median follow-up of 61.3 months [46.9;69], the 5-year overall survival and disease free survival were 98.2 (95% CI=[88.2;99.7]) and 89.5% (95% CI=[76.3;95.6]) respectively. Two delayed invasive relapses occurred leading to one specific death. The pathological review highlighted a trend towards a loss of HR and HER2 expression (9%) in the microinvasive component in comparison with its surrounded in situ carcinoma. CONCLUSION: The risk of initial lymph node involvement and delayed invasive local relapse deserve an optimal locoregional management including lymph node evaluation. The non-negligible discrepancy's rate between in situ and microinvasive components justifies HR status and HER2 expression assessment on the microinvasive component.

[Ductal carcinoma in situ of the breast (DCIS). Histopathological features and treatment modalities: analysis of 1,289 cases]. / Carcinomes canalaires in situ (CCIS). Caractéristiques histopathologiques et traitement : analyse de 1 289 cas.

From March 2003 to April 2004, were prospectively collected in France 1,289 ductal carcinoma in situ (DCIS) with data on diagnosis, patient and tumour characteristics, and treatments. Median age was 56 years (range, 30-84). DCIS was diagnosed by mammography in 87.6% of patients. Mastectomy (M), conservative surgery alone (CS) and conservative surgery with radiotherapy (CS + RT) were performed in 30.5, 7.8 and 61.7% of patients, respectively. Sentinel node biopsy (SNB) and axillary dissection (AD) were performed in 21.3 and 10.4% of patients, respectively. Hormone therapy was administered to 13.4% of the patients. Nuclear grade was low in 21% of patients, intermediate in 38.5% and high in 40.5%. Excision was considered complete in 92% (CS) and 88.3% (CS + RT) of patients. Treatment modalities varied widely according to region: mastectomy rate, 20-37%; adjuvant RT, 84-96%; hormone treatment, 6-34%. Our survey on current DCIS management in France has highlighted correlations between pathological features (tumour size, margin, grade) and treatment options, with several similar variations to those observed in recent UK and US studies.

Factors predicting the sentinel node metastases in T1 breast cancer tumor: an analysis of 1416 cases.

AIM: To determine the factors associated with the metastatic involvement of sentinel lymph node (SLN) biopsy in patients with early breast cancer. STUDY DESIGN: This was a retrospective study of patients with T1 invasive breast cancer who underwent SLN biopsy at Claudius Regaud Institute between January 2001 and September 2008. RESULTS: 1416 patients were recruited into this study. SLN metastases were detected in 368 patients (26%). Younger age, tumor size and location, histological type, nuclear grade, and lymphovascular invasion appear to be significant risk factors of SNL involvement. In multivariate analysis, tumor size, tumor location, histological type and lymphovascular invasion are significant factors. When the tumor size is >20 mm, the OR is 6.6 compared to a T1a tumor (3.145-14.175, p<0.001, confidence interval 95%). When the tumor is found in the inner quadrant, the risk of SLN involvement is reduced compared to external locations with an OR of 0.53 (0.409-0.709, p<0.001, confidence interval 95%). Non-ductal/lobular compared to infiltrative ductal cancer have a lower risk of SLN involvement with an OR of 0.423 (0.193-0.927, p<0.03, confidence interval 95%). Lymphovascular invasion increase the risk of positive SLN with an OR of 2.8 (1.9-4.1, p<0.001, confidence interval 95%). CONCLUSION: It appears reasonable to avoid axillary lymph node dissection in older patients with T1a tumors of good histopathological type and in the absence of lymphovascular invasion.

Chromatographic alignment combined with chemometrics profile reconstruction approaches applied to LC-MS data.

This paper presents a full proteomics analysis LC-MS (Liquid Chromatography-Mass Spectrometry) chain combining bio, nano and information technologies in order to quantify targeted proteins in blood sample. The objective is to enable an early detection of pancreatic cancer. We focus on the data processing step which estimates the proteins' concentration. First, we pre-process the data in order to correct time shift between the experiments. We propose to use block matching algorithm. Second, quantification of protein is performed using chemometrics approaches and more precisely CLS, PLS, N-PLS and PARAFAC algorithms. Performances of the various methods have been compared on cytochrome c protein LC-MS analyses.

Selective inhibition of HER2 inhibits AKT signal transduction and prolongs disease-free survival in a micrometastasis model of ovarian carcinoma.

Although first-line chemotherapy induces complete clinical remission in many cases of epithelial ovarian cancer, relapse usually occurs 18-28 months from diagnosis owing to micrometastases. The present study aimed to evaluate the effect of trastuzumab on disease-free and overall survival in a specially designed murine model of ovarian cancer (OVCAR-3), which mimicked the natural history of human micrometastatic disease. Trastuzumab can cure the mice if started soon after induction chemotherapy. It can modestly inhibit the proliferation through mitogen-activated protein kinase signal transduction and clearly inhibit AKT phosphorylation, which is involved in survival pathway. As OVCAR-3 cell lines show no HER2 amplification or overexpression, these results warrant further studies to assess the efficacy of trastuzumab in the early stage of relapse in cancer models other than those overexpressing HER2.