An immunological signature to predict outcome in patients with triple-negative breast cancer with residual disease after neoadjuvant chemotherapy.

BACKGROUND: When triple-negative breast cancer (TNBC) patients have residual disease after neoadjuvant chemotherapy (NACT), they have a high risk of metastatic relapse. With immune infiltrate in TNBC being prognostic and predictive of response to treatment, our aim was to develop an immunologic transcriptomic signature using post-NACT samples to predict relapse. MATERIALS AND METHODS: We identified 115 samples of residual tumors from post-NACT TNBC patients. We profiled the expression of 770 genes related to cancer microenvironment using the NanoString PanCancer IO360 panel to develop a prognostic transcriptomic signature, and we describe the immune microenvironments of the residual tumors. RESULTS: Thirty-eight (33%) patients experienced metastatic relapse. Hierarchical clustering separated patients into five clusters with distinct prognosis based on pathways linked to immune activation, epithelial-to-mesenchymal transition and cell cycle. The immune microenvironment of the residual disease was significantly different between patients who experienced relapse compared to those who did not, the latter having significantly more effector antitumoral immune cells, with significant differences in lymphoid subpopulations. We selected eight genes linked to immunity (BLK, GZMM, CXCR6, LILRA1, SPIB, CCL4, CXCR4, SLAMF7) to develop a transcriptomic signature which could predict relapse in our cohort. This signature was validated in two external cohorts (KMplot and METABRIC). CONCLUSIONS: Lack of immune activation after NACT is associated with a high risk of distant relapse. We propose a prognostic signature based on immune infiltrate that could lead to targeted therapeutic strategies to improve patient prognosis.

The risk of postoperative complications and functional impairment after multimodality treatment for limb and trunk wall soft-tissue sarcoma: Long term results from a monocentric series.

BACKGROUND AND OBJECTIVES: Conservative surgery for soft-tissue sarcoma (STS) within multimodality treatment attempts to reconcile two contradictory requirements: assuring a good oncological outcome through a wide resection and preserving the function. The aim of our study is to verify whether our conservative approach to STS met these objectives. METHODS: A retrospective database analysis was performed in adults with primary limb or trunk wall STS operated in a single center from 1989 to 2012. Predictive factors for postoperative complications and functional impairment were tested in a multivariate analysis. RESULTS: 728 patients were operated (resection R0: 68%). Neoadjuvant chemotherapy (NAC) was given to 28%, postoperative radiotherapy to 70% of patients. Median follow-up was 103 months. At five years, overall survival was 80% and local recurrences 11%. Major postoperative complications occurred in 8% and functional impairment in 13% of the patients. Independent predictive factors for postoperative complications were American Society of Anesthesiologist classes 2 and 3 (OR: 2.3, CI: 1.2-4.5 and 4.0 CI: 1.7-9.3), tumor size >80 mm (OR: 2.5, CI: 1.3-4.9), tumor site (trunk wall/lower limb, OR: 4.1, CI: 1.3-13.6) and multifocal/multicompartmental spread (OR: 2, CI: 1.1-3.6). Independent predictive factors for function impairment were postoperative complications (OR: 5.3, CI: 2.8-10.1), NAC (OR: 3.6, CI: 2.2-5.8), and bone or neurovascular involvement (OR 3.3, CI 2.0-5.3), whereas Early Rehabilitation after Surgery (ERAS) improved outcome (OR: 0.5, CI: 0.3-0.9). CONCLUSION: Postoperative complications induced functional impairment. They may be reduced by acting on comorbidity factors and careful tumor evaluation prior to surgery. Furthermore, ERAS measures improved function.

Predictive factors of depressive symptoms of elderly patients with cancer receiving first-line chemotherapy.

BACKGROUND: Depression is the most common psychiatric disorder in geriatrics and oncology. For elderly cancer patients, it has a significant impact on quality of life, morbidity, and mortality. Nevertheless, depression is under-diagnosed and under-treated. Cancer management is key in improving the quality of care in this population. We aim to identify sociodemographic, clinical, and treatment-related factors of depression in elderly patients during chemotherapy, thus allowing early detection of patients in need of specific treatment. Further, we investigate whether chemotherapy efficacy and safety are associated with depression. PATIENTS AND METHODS: A prospective multicenter cohort composed of incident cases of cancer diagnosed in patients 70 years and older, receiving first-line chemotherapy. Depressive symptoms were measured by the Geriatric Depression Scale at baseline and after four chemotherapy cycles. Associations between depressive symptoms during chemotherapy and patients' clinical and treatment characteristics were identified by logistic regression. RESULTS: Among 344 patients measured for depression before chemotherapy, 260 had a second assessment at the fourth treatment cycle. At baseline, 45.4% were depressed, and 44.6% were depressed after the fourth cycle. Independent factors of depression were depressive symptoms at baseline (odds ratio (OR) = 6.7, p < 0.001), malnutrition (OR = 5.1, p = 0.014), and risk of malnutrition (OR = 1.6, p = 0.014). After controlling for missing data, effective chemotherapy was associated with a lower risk of depression (OR = 0.4, p = 0.018). CONCLUSION: We highlight the role of depressive symptoms and nutritional status at baseline, on the occurrence of depressive symptoms during chemotherapy. These factors should be taken into account in any pre-treatment consultation and appropriate nutritional and psychiatric preventative measures established. Copyright © 2016 John Wiley & Sons, Ltd.

Soft tissue masses with myxoid stroma: Can conventional magnetic resonance imaging differentiate benign from malignant tumors?

OBJECTIVES: To retrospectively evaluate the diagnostic performance of morphological signs observed on conventional magnetic resonance (MR) imaging to differentiate benign from malignant peripheral solid tumors of soft tissue with myxoid stroma. METHODS: MR images from 95 consecutive histopathologically proven tumors (26 benign and 69 malignant) of soft tissues with myxoid components were evaluated in our tertiary referral center. Two radiologists, blind to pathology results, independently reviewed conventional MR sequences including at least a) one T2-weighted sequence with or without fat suppression; b) one T1-weighted sequence without fat suppression; and c) one T1-weighted sequence with gadolinium-complex contrast enhancement and fat suppression. Multiple criteria were defined to analyze morphology, margins, architecture and tumor periphery and evaluated for each lesion. Intra- and inter-observer reproducibility and Odds ratios were calculated for each criterion. RESULTS: The most relevant and reproducible criteria to significantly predict malignancy were: (1) ill-defined tumor margins, (2) a hemorrhagic component, (3) intra-tumoral fat, (4) fibrosis and (5) the "tail sign". A lesion is classified as malignant if any of these 5 criteria is present, and benign if none of them are observed. Therefore, this combination provides a sensitivity of 92.9% and a specificity of 93.3%. CONCLUSION: Conventional MR imaging provides reproducible criteria that can be combined to differentiate between benign and malignant solid tumors of soft tissue with myxoid stroma.

The introduction of early patient rehabilitation in surgery of soft tissue sarcoma and its impact on post-operative outcome.

BACKGROUND: Enhanced recovery after surgery (ERAS) programs are implemented in multiple fields of surgery, but not yet in soft-tissue sarcoma (STS) surgery. We wondered whether its introduction into STS surgery might have impacted postoperative outcome. METHODS: Two hundred and fifty seven adult patients with primary limb or trunk wall STS received ERAS from 2008 to 2012 as a part of the intra-operative management. We evaluated, in retrospect, the intra-operative management, post-operative outcomes, functional and oncological results of these patients and compared them with 459 prior patients treated under a standard recovery after surgery (SRAS) program from 1989 to 2007. RESULTS: The most visible change from SRAS to ERAS in the perioperative management was decrease of wound drainage (72% vs. 15%, p < 0.001) and increase of wound bandaging (16% vs. 66%; p < 0.001), underlining the appliance of the ERAS protocol. Post-operatively, hospital stay dropped from nine (0-74) to three (0-22) days (p < 0.001) without affecting major morbidity (8% vs. 5%, NS) or readmission to the hospital (5% vs. 4%, NS). Functional outcome improved (p = 0.009) but whether this change was due to ERAS remains to be proved because complementary treatments changed over time. Tumour control remained unaffected, with an estimated risk of local recurrence at 5 years of 12% in both groups. CONCLUSION: Introducing a rapid recovery program was associated with a shorter hospitalization stay without compromising surgical or oncological outcomes. The program appears to be safe and reliable to use in patients undergoing STS surgery.

Retroperitoneal sarcomas: patterns of care at diagnosis, prognostic factors and focus on main histological subtypes: a multicenter analysis of the French Sarcoma Group.

BACKGROUND: Retroperitoneal sarcomas (RPS) are heterogeneous. No previous study has investigated the impact of specialized surgery, evaluated locoregional relapse (LRR), abdominal sarcomatosis and distant metastatic relapse as separate events, or considered histological subtypes separately. This study addresses these specific points in a homogeneous cohort of patients with completely resected primary RPS. PATIENTS AND METHODS: We conducted a retrospective analysis of adult patients diagnosed with a RPS between 1 January 1988 and 31 December 2008 and eventually referred to one of 12 centers of the French Sarcoma Group. All cases were centrally reviewed by an expert pathologist. RESULTS: Five hundred eighty-six patients were included. Median follow-up was 6.5 years [95% confidence interval (CI) 5.9-7.1]. Five hundred thirty-seven patients had localized disease and 389 patients (76%) had macroscopically complete resection of the tumor. In this latter group, the 5-year LRR-free survival rate was 46% [41-52] and the 5-year overall survival (OS) rate was 66% [61-71]. In multivariate analysis, gender, adjacent organ involvement, specialization of the surgeon, piecemeal resection and perioperative radiotherapy were independently associated with LRR. Specialization of the surgeon and piecemeal resection were independently associated with abdominal sarcomatosis whereas histology and adjacent organ involvement were independently associated with distant metastasis. Age, gender, grade, adjacent organ involvement and piecemeal resection were significantly associated with OS. Prognostic factors for LRR and OS were analyzed in well-differentiated and dedifferentiated liposarcomas and leiomyosarcomas. Grade 3 was an independent prognostic factor for OS of dedifferentiated liposarcomas. CONCLUSION: This study underlines the crucial role of pretherapeutic assessment and meticulous histological examination of RPS as well as the need to consider histological subtypes separately. Surgery in a specialized center and avoidance of piecemeal resection stand out as the two most important prognostic factors for RPS and highlight the importance of treating these patients in specialized centers.

Retroperitoneal sarcomas: patterns of care in advanced stages, prognostic factors and focus on main histological subtypes: a multicenter analysis of the French Sarcoma Group.

BACKGROUND: Retroperitoneal sarcomas (RPS) are heterogeneous. Advanced stages include unresectable locoregional (LR) disease, abdominal sarcomatosis and distant metastasis. There is no available report assessing palliative chemotherapy in advanced RPS. This study analyzes management and outcome in a large cohort of patients with advanced RPS, considering main histological subtypes separately. PATIENTS AND METHODS: We conducted a retrospective analysis of adult patients diagnosed with a RPS between 1 January 1988 and 31 December 2008 across 12 centers of the French Sarcoma Group. All cases were centrally reviewed by an expert pathologist. RESULTS: Five-hundred eighty-six patients were included, 299 patients received palliative chemotherapy, with a median of two lines (range 0-8). Fifty patients underwent palliative surgery. Two hundred fifty-five patients (85%) were assessable for response after first line of chemotherapy. Among them, 69 patients (27%) had progressive disease, 145 (57%) had stable disease, 37 (14.5%) had partial response and 4 (1.5%) complete response. Median time from first line of palliative chemotherapy to progression was 5.9 months [4.9-7.3] and median overall survival (OS), 15.8 months [13-18]. In multivariate analysis, prognosis factors independently associated with poor OS were male gender, performance status (PS) >1 and grade >1. There was no difference according to stage of disease. Palliative surgery did not appear to add any survival benefit. CONCLUSION: These results emphasize the scarcity of available options for RPS in the advanced setting and the urgent need to develop new strategies. Patients with good PS should be included in clinical trials and best supportive care should be considered in those with poor PS.

Liver metastases in close contact to hepatic veins ablated under vascular exclusion.

BACKGROUND: Liver metastases (LM) in close contact to hepatic veins (HV) are a frequent cause of unresectability. Reconstruction of hepatic veins is technically difficult and outcomes are poor. Intra-operative radiofrequency ablation (IRFA) with vascular exclusion (VE) may be a useful approach. METHODS: Out of 358 patients operated for LM, 22 with LM close to a HV treated by IRFA under VE with at least one year of follow-up were included in this retrospective study. Technical success was evaluated at four months by CT scan of the ablated lesion. Complications; local, hepatic and extra-hepatic recurrence rates, and overall survival are reported. RESULTS: The median number of metastases was 4.5 [range: 1-12]. Seventeen patients had bilateral metastases. The median size of ablated lesions was 2 cm [range: 1-5.5]. Seven complications occurred (1 Grade 1, 2 Grade 3b and 4 Grade IVa), with no mortality. No recurrence of ablated lesions was detected at four months or during follow-up. Seventeen patients had new or extra-hepatic lesions. Median overall survival for colorectal patients was 40 months 95%CI[17.5-not reached]. CONCLUSIONS: IRFA plus VE for LM in close contact to a HV is a novel approach, appearing to be a safe and effective technique which can extend the applications of liver metastases surgery.

Docetaxel rechallenge after a first response in non-resistant metastatic breast cancer: significant activity with manageable toxicity.

Docetaxel is a major drug in metastatic breast cancer (MBC) treatment. At progression, rechallenge with docetaxel can be discussed, according to previous efficacy and tolerance, as long as it was stopped for reasons other than progression. Currently, no data are available outlining outcomes after this pragmatic approach in MBC. We retrospectively identified 72 patients with the following criteria: (i) objective response or stable disease with a previous line of treatment with docetaxel in the metastatic setting, (ii) discontinuation for a reason other than progression, (iii) rechallenge with docetaxel after a minimal docetaxel-free interval of 3 months. The main objectives were to evaluate overall response (ORR), time to progression (TTP), overall survival (OS) and toxicity at reintroduction of docetaxel. Median patient age was 57 years (range: 34-84). Docetaxel was reintroduced as a 2nd, 3rd, or ≥4th line of chemotherapy in the metastatic setting in 21, 46 and 33% of cases, respectively. Previous agents used included capecitabine, anthracycline, and vinorelbine in 54, 40 and 21% of cases, respectively. The median number of docetaxel cycles was 6 (range: 1-18). Among the 33 patients with disease assessed according to RECIST criteria, 14 (42.5%) had a partial response and 11 (33.5%) a stable disease>6 weeks. Among the 46 patients with an initial CA 15-3 increase, 34 (74%) had a ≥50% decrease of the value. Globally, 55 patients (76%) obtained a benefit from the treatment. The median TTP and OS were 5.7 months (95% CI: 5.0-6.3) and 10.2 months (95% CI: 8.6-11.8), respectively. Forty-six patients (64%) reported grade 1/2 toxicity, 23 patients (32%) experienced grade 3/4 toxicity, mostly neutropenia (17%) and fluid retention (10%). There was no difference in median TTP after subsequent docetaxel in subgroup analyses. This retrospective analysis supports the pragmatic strategy to retreat patients with MBC with docetaxel when this drug has shown previous activity and was stopped for other causes than progression.

Radiological features of triple-negative breast cancers (73 cases).

OBJECTIVES: Triple-negative breast cancers generally occur in young women and they have the potential to be aggressive. It is important for this subtype of tumour to be detected early. We studied the appearance of 73 tumours on mammography, sonography and MRI in order to determine what specific features they showed on imaging. PATIENTS AND METHODS: From July 2009 to December 2010, we retrospectively reviewed mammogram and sonogram images of 73 triple-negative cancers. Colour Doppler had been used to depict vascularisation in 34 cases and elastography score calculated in 17 cases. Sixteen patients had undergone MRI. The radiological description of these different modalities draws on the BI-RADS lexicon and categorisation. RESULTS: On mammography, triple-negative cancers often presented as a round mass (59.3%) or an oval or lobulated mass (65%), with circumscribed (15%), microlobulated (12.5%), indistinct (55%) or occasionally spiculated margins (15%). On sonography, the vast majority of these cancers appeared as masses (92.8%) with occasional posterior acoustic attenuation (22.6%). MRI showed more suspicious images than the standard examinations, notably rim-enhancement (eight out of 12 masses). CONCLUSION: . Radiological images appear as lobulated masses more readily, while on sonography posterior enhancement is shown more often than attenuation, and MRI finds rim-enhancement.

[Hodgkin's disease and breast cancer: for which patients is there an association? A series from Institut Bergonié]. / Maladie de Hodgkin et cancer du sein: une association pour quelles patientes ? À propos d'une série de l'institut Bergonié

OBJECTIVE: Breast cancer is the most frequent secondary tumor for women treated for Hodgkin's disease. It is important to study the risk factors associated to be able to adapt the monitoring of these women. PATIENTS AND METHODS: This is a retrospective study from Institut Bergonié, a comprehensive French Cancer Center, concerning the women treated for Hodgkin's disease and having developed a breast cancer. RESULTS: Among 328 women treated for Hodgkin's disease between January 1968 and December 1994, 20 patients developed 25 breast cancers. The average age of the patients during the irradiation was 24 years and the average period of occurrence of the cancer was 19 years. An irradiation of the chest wall and an under-diaphragmatic irradiation in doses of 40Gy are risk factors for the occurrence of breast cancer. A young age, less than 30, in the treatment of Hodgkin's disease tend to be significant. DISCUSSION AND CONCLUSION: This population of women with a high risk of breast cancer thus has to benefit from an appropriate monitoring program, which is what we suggest setting up in the Institut Bergonié.

Sarcoma lung metastases treated with percutaneous radiofrequency ablation: results from 29 patients.

PURPOSE: We aimed to determine safety and efficacy of radiofrequency ablation (RFA) in the treatment of lung metastases arising from sarcoma. METHODS: Between 2002 and 2009, 29 patients (mean age 51 years) treated for metastatic sarcoma with a maximum of 5 lung metastases treatable with RFA were followed prospectively. The end points were local efficacy (assessed by computed tomography during the follow-up period), complications, and survival (overall and disease-free). RESULTS: A total of 47 metastases were treated with RFA. Median follow-up time was 50 months (range 28-72 months). Pneumothorax was the most frequent complication and occurred in 68.7% of the procedures. The 1- and 3-year survival rates were 92.2% (95% confidence interval [CI] 0.73-0.98) and 65.2% (95% CI 0.42-0.81), respectively. Disease-free survival was 7 months (95% CI 3.5-10). Five recurrences on RFA sites were noted during follow-up. CONCLUSIONS: RFA is safe and efficient in the treatment of lung metastasis originating from sarcomas. RFA may provide a low-morbidity alternative to surgery, being less invasive and preserving the patient's ability to undergo possible repeat operations.

Performance status is the most powerful risk factor for early death among patients with advanced soft tissue sarcoma: the European Organisation for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group (STBSG) and French Sarcoma Group (FSG) study.

BACKGROUND: We investigated prognostic factors (PFs) for 90-day mortality in a large cohort of advanced/metastatic soft tissue sarcoma (STS) patients treated with first-line chemotherapy. METHODS: The PFs were identified by both logistic regression analysis and probability tree analysis in patients captured in the Soft Tissue and Bone Sarcoma Group (STBSG) database (3002 patients). Scores derived from the logistic regression analysis and algorithms derived from probability tree analysis were subsequently validated in an independent study cohort from the French Sarcoma Group (FSG) database (404 patients). RESULTS: The 90-day mortality rate was 8.6 and 4.5% in both cohorts. The logistic regression analysis retained performance status (PS; odds ratio (OR)=3.83 if PS=1, OR=12.00 if PS ≥2), presence of liver metastasis (OR=2.37) and rare site metastasis (OR=2.00) as PFs for early death. The CHAID analysis retained PS as a major discriminator followed by histological grade (only for patients with PS ≥2). In both models, PS was the most powerful PF for 90-day mortality. CONCLUSION: Performance status has to be taken into account in the design of further clinical trials and is one of the most important parameters to guide patient management. For those patients with poor PS, expected benefits from therapy should be weighed up carefully against the anticipated toxicities.

High frequency of beta-catenin heterozygous mutations in extra-abdominal fibromatosis: a potential molecular tool for disease management.

BACKGROUND: Fibromatosis comprises distinct clinical entities, including sporadic extra-abdominal fibromatosis, which have a high tendency for recurrence, even after adequate resection. There are no known molecular biomarkers of local recurrence. We searched for beta-catenin mutations in a European multicentre series of fibromatosis tumours to relate beta-catenin mutational status to disease outcome. METHODS: Direct sequencing of exon 3 beta-catenin gene was performed for 155 frozen fibromatosis tissues from all topographies. Correlation of outcome with mutation rate and type was performed on the extra-abdominal fibromatosis group (101 patients). RESULTS: Mutations of beta-catenin were detected in 83% of all cases. Among 101 extra-abdominal fibromatosis, similar mutation rates (87%) were observed, namely T41A (39.5%), S45P (9%), S45F (36.5%), and deletion (2%). None of the clinico-pathological parameters were found to be significantly associated with beta-catenin mutational status. With a median follow-up of 62 months, 51 patients relapsed. Five-year recurrence-free survival was significantly worse in beta-catenin-mutated tumours regardless of a specific genotype, compared with wild-type tumours (49 vs 75%, respectively, P=0.02). CONCLUSION: A high frequency (87%) of beta-catenin mutation hallmarks extra-abdominal fibromatosis from a large multicentric retrospective study. Moreover, wild-type beta-catenin seems to be an interesting prognostic marker that might be useful in the therapeutic management of extra-abdominal fibromatosis.

[Prognostic impact of tumour volume and lymph node involvement in intermediate stage T1b1 to T2b cancer of the uterine cervix]. / Impact pronostique du volume tumoral et du statut ganglionnaire dans les cancers du col de l'utérus de stades intermédiaires T1b1 à T2b.

OBJECTIVE: Determine the prognostic significance of tumour volume and pelvic lymph node status in intermediate stage T1b1 to T2b cancers of the uterine cervix. PATIENTS AND METHODS: Multivariate prognostic factor study in 219 patients (pts), median age 48 years, with stage T1b1 > 2 cm to T2b cervical cancers treated in 91% by primary radio- +/- chemotherapy. All had a pretherapeutic laparoscopic pelvic lymphadenectomy, and 166 pts. had their tumour volume assessed by MRI. Patient and tumour characteristics were considered for analysis. RESULTS: Significant prognostic variables in univariate analysis were the ASA anaesthetic score, stage T2b, tumour diameter, involvement of the uterine corpus, radiological (N1) and histological (N+) pelvic lymph node involvement and bilateral N+. Tumour volume was not significant. In multivariate analysis stage T2b (HR = 2.5; p = 0.003), N+ (HR = 3; p = 0.003) and bilateral N+ (HR = 6.1; p < 0.0001) were independent prognostic factors. Four prognostic groups according the existence of 0 to 3 prognostic factors showed their overall survivals declining from 97 to 27% (p < 0.0001). CONCLUSION: Stage T2b and pelvic lymph node involvement, but not tumour volume, are the major prognostic factors in intermediate stage cervical cancers. Pelvic lymph node involvement should be determined before treatment.

Soft tissue sarcomas of the trunk wall (STS-TW): a study of 343 patients from the French Sarcoma Group (FSG) database.

BACKGROUND: Soft tissue sarcomas of the trunk wall (STS-TW) are usually studied together with soft tissue sarcomas of other locations. We report a study on STS-TW forming part of the French Sarcoma Group database. PATIENTS AND METHODS: Three hundred and forty-three adults were included. We carried out univariate and multivariate analysis for overall survival (OS), metastasis-free survival (MFS) and local recurrence-free survival (LRFS). RESULTS: Tumor locations were as follows: thoracic wall, 82.5%; abdominal wall, 12.3% and pelvic wall, 5.2%. Median tumor size was 6.0 cm. The most frequent tumor types were unclassified sarcoma (27.7%) and myogenic sarcoma (19.2%). A total of 44.6% of cases were grade 3. In all, 21.9% of patients had a previous medical history of radiotherapy (PHR). Median follow-up was 7.6 years. The 5-year OS, MFS and LRFS rates were 60.4%, 68.9% and 58.4%, respectively. Multivariate analysis retained PHR and grade for predicting LRFS and PHR, size and grade as prognostic factors of MFS. Factors influencing OS were age, size, PHR, depth, grade and surgical margins. The predictive factors of incomplete response were PHR, size and T3. CONCLUSIONS: Our results suggest similar classical prognostic factors as compared with sarcomas of other locations. However, a separate analysis of STS-TW revealed a significant poor prognosis subgroup of patients with PHR.

Impact of immunohistochemical markers, CK5/6 and E-cadherin on diagnostic agreement in non-invasive proliferative breast lesions.

AIMS: To assess the impact of cytokeratin (CK) 5/6 and E-cadherin immunohistochemistry on diagnostic agreement of non-invasive proliferative breast lesions. METHODS AND RESULTS: Twenty pathologists classified 105 cases of non-invasive proliferative breast lesions into 10 diagnostic categories. One haematoxylin and eosin (H&E) slide of each case was analysed on a first round and one H&E slide with corresponding CK5/6 and E-cadherin immunohistochemistry was analysed on a second round. Interobserver reproducibility for category-specific and management-specific lesions was measured on each round. CK5/6 and E-cadherin had little impact on diagnostic agreement, which remained moderate between the first and second rounds (overall kappa coefficients of 0.47 and 0.53, respectively, P = NS). Levels of agreement slightly improved for lesions with specific CK5/6 and E-cadherin immunoprofiles (usual ductal hyperplasia, atypical ductal hyperplasia, atypical lobular hyperplasia, lobular carcinoma in situ, non-high-grade ductal carcinoma in situ), but the differences observed were not statistically significant. However, diagnostic agreement improved when lesions were grouped according to their management category (overall kappa coefficients of 0.58 and 0.66 in the first and second rounds, respectively). CONCLUSIONS: CK5/6 and E-cadherin immunohistochemistry has little impact on interobserver reproducibility for non-invasive breast lesions. Diagnostic agreement can, however, be improved by grouping lesions in management categories.

[Laparoscopic interiliacal lymphadenectomy in cancer of the uterine cervix: still the gold standard? A propos lymph node recurrences in 190 treated patients]. / Lymphadénectomie inter-iliaque per-coelioscopique dans le cancer du col de l'utérus: toujours le gold standard? A propos des rechutes ganglionnaires après lymphadénectomie chez 190 patientes traitées.

OBJECTIVE: To determine the reliability of pretherapeutic laparoscopic pelvic lymphadenectomy in cervical cancer as a function of lymph node recurrences according to initial lymph node status: 1) to establish the false negative rate by analyzing lymph node recurrence in patients N-, 2) to verify treatment adequacy in patients N+ by comparing the rate of node recurrence to initial node positivity. PATIENTS AND METHODS: Retrospective analysis of a prospectively registered patient database. One hundred and ninety patients treated by a combination of radiotherapy and surgery for cervical cancer stages 1b to 2b in 95% of cases had undergone, from March 1992 to June 2003, a previous laparoscopic pelvic lymphadenectomy. Median follow-up was 40 months (range: 3-126 months). RESULTS: Initial lymph node positivity (N+) was found in 79 patients (42%). Fourteen patients (7.4%) presented with lymph node recurrence, all of whom have died from disease. Lymph node recurrence was found in 4/111 patients N- (3.6%) and in 10/79 patients N+ (12.7%), of whom 8/10 occurred outside the radiation fields. CONCLUSION: With a very low false negative rate, accuracy of the laparoscopic pelvic lymphadenectomy in the determination of lymphatic spread in cervical cancer is confirmed. It can still be considered the gold standard despite recent developments (e.g. sentinel lymph node determination) to which they should be compared. Treatment adequacy in patients N+ is confirmed.

[Adjuvant radiation therapy for soft tissue sarcoma of the extremities: analysis of local control according to volume and dose]. / Radiothérapie adjuvante des sarcomes des tissus mous des membres: analyse du contrôle local en fonction des volumes irradiés et de la dose.

PURPOSE: To evaluate retrospectively the anatomical definition of target volumes in the treatment of soft tissue sarcomas of the limbs and to study the radiation dose in the local control and toxicity. METHODS AND PATIENTS: Seventy-seven patients were consecutively treated for primary soft tissue sarcoma of the extremity with limb sparing surgery and external beam radiotherapy (EBRT) in the same institution. The median follow up was 56 months (17-89 months). RESULTS: Fifty-two patients (67%) had clear microscopic surgical margin (R0 resection), 23 (30%) had histologically positive microscopic margin (R1 resection), 2 had a macroscopic residual disease (R2 resection). An anatomical definition of target volumes has been realised. The mean dose was 50 Gy in 25 or 28 fractions; 23 patients received a boost restricted to the tumor bed: 13 with EBRT, 10 with brachytherapy (BRT). Thirty-four patients had an adjuvant chemotherapy. The overall 5 year local relapse rate was 10%. Seven local relapses were described, five of the high-grade tumours, and five in patients with positive margin. In univariate analysis, quality of surgery shows a significant effect for local control. By using LENT-SOMA scale for late toxicity, a significant difference was found for neurological complications for patients receiving a boost. CONCLUSIONS: The results of the series validate the concept of anatomical definition of the initial target volume. A boost should be realised for positive margin tumors and may be for high-grade tumors. Neurological toxicity must be considered for the evaluation of the prescribed dose.

[Prevention of infectious complications after cesarean section by the use of cefotetan]. / Prévention par l'utilisation du céfotétan des complications infectieuses après césarienne.

A prospective, randomised study was carried out on 110 patients to find out the effect of giving Cefotetan prophylactically as against no treatment in the prevention of infections after cesarean sections. The cases were selected before or at the beginning of a trial of labour in 72 cases and after a failure of trial of labour in 38 cases. A single dose of 2 gr of Cefotetan was given during the operation, after the cord had been clamped. It caused a significant drop in infection and in particular the number of cases of endometritis and urinary tract infections, which were twice as common in the non-treated as compared with the treated group.