Surgical Management of Benign and Borderline Phyllodes Tumors of the Breast.

Phyllodes tumors (PT) are uncommon fibroepithelial breast neoplasms and there is currently no clear consensual treatment for these tumors. The aim of our study was to evaluate the surgical management and outcome of benign and borderline PT. We retrospectively assessed 76 cases of benign or borderline PT managed at the Leon Berard comprehensive cancer center in Lyon, France between July 2003 and December 2013. The mean age at diagnosis was 37.9 years and the median follow-up was 58 months. Seventy-five patients (99%), with a mean tumor size of 27 mm, underwent a breast-conserving procedure. The tumor margins were considered positive (when the tumor was present at the inked surgical section) in seven of 76 cases (9%) and negative in 65 out of 76 cases (86%). We observed the presence of small negative surgical margins <10 mm in 89% and <1 mm in 71% of the patients. Although no re-excision was performed to increase these margins, we did not see any increase in the local recurrence rate (4%) when compared to recurrence rates reported in the literature. We thus suggest that systematic revision surgery for close or positive surgical margins for benign PT should not be systematically performed. However, as recurrences occur within 2 years of initial excision, we recommend a regular clinical and imaging follow-up especially during this period for which patient's compliance is essential.

TIF1γ interferes with TGFß1/SMAD4 signaling to promote poor outcome in operable breast cancer patients.

BACKGROUND: The Transforming growth factor ß (TGFß) signaling has a paradoxical role in cancer development and outcome. Besides, the prognostic significance of the TGFß1, SMAD4 in breast cancer patients is an area of many contradictions. The transcriptional intermediary factor 1γ (TIF1γ) is thought to interact with the TGFß/SMAD signaling through different mechanisms. Our study aims to define the prognostic significance of TGFß1, SMAD4 and TIF1γ expression in breast cancer patients and to detect possible interactions among those markers that might affect the outcome. METHODS: Immunohistochemistry was performed on tissue microarray (TMA) blocks prepared from samples of 248 operable breast cancer patients who presented at Centre Léon Bérard (CLB) between 1998 and 2001. The intensity and the percentage of stained tumor cells were integrated into a single score (0-6) and a cutoff was defined for high or low expression for each marker. Correlation was done between TGFß1, SMAD4 and TIF1γ expression with the clinico-pathologic parameters using Pearson's chi-square test. Kaplan-Meier method was used to estimate distant metastasis free survival (DMFS), disease free survival (DFS) and overall survival (OS) and the difference between the groups was evaluated with log-rank test. RESULTS: 223 cases were assessable for TIF1γ, 204 for TGFß1 and 173 for SMAD4. Median age at diagnosis was 55.8 years (range: 27 to 89 years). Tumors were larger than 20 mm in 49.2% and 45.2% had axillary lymph node (LN) metastasis (N1a to N3). 19.4% of the patients had SBR grade I tumors, 46.8% grade II tumors and 33.9% grade III tumors. ER was positive in 85.4%, PR in 75.5% and Her2-neu was over-expressed in 10% of the cases. Nuclear TIF1γ, cytoplasmic TGFß1, nuclear and cytoplasmic SMAD4 stainings were high in 35.9%, 30.4%, 27.7% and 52.6% respectively. TIF1γ expression was associated with younger age (p=0.006), higher SBR grade (p<0.001), more ER negativity (p=0.035), and tumors larger than 2 cm (p=0.081), while TGFß1 was not associated with any of the traditional prognostic factors. TGFß1 expression in tumor cells was a marker of poor prognosis regarding DMFS (HR=2.28; 95% CI: 1.4 to 3.8; p=0.002), DFS (HR=2.00; 95% CI: 1.25 to 3.5; p=0.005) and OS (HR=1.89; 95 % CI: 1.04 to 3.43; p=0.037). TIF1γ expression carried a tendency towards poorer DMFS (p=0.091), DFS (p=0.143) and OS (p=0.091). In the multivariate analysis TGFß1 remained an independent predictor of shorter DMFS, DFS and OS. Moreover, the prognostic significance of TGFß1 was more obvious in the TIF1γ high patient subgroup than in the patients with TIF1γ low expression. The subgroup expressing both markers had the worst DMFS (HR=3.2; 95% CI: 1.7 to 5.9; p<0.0001), DFS (HR=3.02; 95 % CI: 1.6 to 5.6; p<0.0001) and OS (HR=2.7; 95 % CI: 1.4 to 5.4; p=0.005). CONCLUSION: There is a crosstalk between the TIF1γ and the TGFß1/SMAD4 signaling that deteriorates the outcome of operable breast cancer patients and when combined together they can serve as an effective prognostic tool for those patients.

The incidence and clinical significance of the micrometastases in the sentinel lymph nodes during surgical staging for early endometrial cancer.

INTRODUCTION: The status of regional node remains one of the most important factors to guide adjuvant therapy in endometrial cancer (EC). Pelvic recurrence occurs in up to 15% of early EC patients with negative pelvic lymph nodes (LNs). The prognostic significance of detecting micrometastases (µM) in LN is debated. This retrospective case-control study performed in the Oncological Gynecology Department in Lyon between December 1998 and June 2012 reports the incidence and the clinical significance of µM detected during ultrastaging of negative sentinel lymph node (SLN) in EC. PATIENTS AND METHODS: Ninety-three patients affected by type I and II EC were submitted to surgery with SLN. Dual-labeling method was used to detect SLN. All the SLNs were subjected to ultrastaging researching µM. The patients with a locoregional or distant relapse represented the case-series (CS). The patients without locoregional or distant recurrences were the case-controls (CC).They were matched (1:2 ratio) according to age, International Federation of Gynecology and Obstetrics stage, and histopathologic features. RESULTS: Ten patients presenting a relapse represented CS. In the remaining 83 patients without recurrence, 20 CC were individualized. The detection rate of SLN per hemipelvis was of 17 (85%) of 20 hemipelvis and of 33 (82.5%) of 40 hemipelvis for CS and CC, respectively. Two SLN of CS arm were positives at frozen section. One of the 8 patients of CS arm with negative SLNs was positive for µM by immunohistochemistry analysis. CONCLUSIONS: Lymph node status is one of the most important histopathologic features to determine the adjuvant treatment. The SLN technique could be proposed in selected patients affected by early EC. The µM in SLN could be researched and could help to modulate the following treatment. The multicenter study must be performed to clarify the optimal method of research of SLN in EC and the significance of µM in the LN.

Primary ovarian borderline tumor in the inguinal lymph node.

We report the case of a primary serous ovarian borderline tumour developed in an inguinal lymph node. No primary ovarian borderline tumour was observed within the ovaries after bilateral ovariectomy and complete pathological examination. We considered the diagnosis of ectopic ovarian tissue because the tumour was completely surrounded by normal ovarian tissue with positive FOXL2 staining. The whole ovarian tissue was itself entirely surrounded by lymphatic tissue. Two other hypotheses should be considered: primary retroperitoneal borderline tumour or retroperitoneal nodal involvement by an ovarian serous borderline tumour. Ectopic ovarian tissue can be observed in lymph node. We don't believe ectopic location of ovarian tissue increase the risk of neoplastic change.

Coagulation assessment by rotation thrombelastometry in normal pregnancy.

We analysed changes in coagulation during normal pregnancy with a novel point-of-care device based on thrombelastometry (ROTEM). We compared the results obtained with those of standard coagulation tests in 104 patients: 20 non-pregnant women (controls) and 84 women in the first (T1, n = 17), second (T2, n = 9) and third (T3, n = 58) trimesters of pregnancy. We measured the clotting time (CT), the maximum clot firmness (MCF), the early clot amplitude at 5 and 15 minutes (CA(5), CA(15)) and the clot lysis index (CLI(30)) with four tests containing specific reagents. (a) The INTEM test involving ellagic acid activated the intrinsic pathway and (b) the EXTEM test using tissue factor triggered the extrinsic pathway; (c) The FIBTEM test based on a platelet inhibitor (cytochalasin D) evaluated the contribution of fibrinogen to clot formation and (d) the APTEM test was similar to the EXTEM but was based on inhibition in vitro of fibrinolysis by aprotinin. CT and CLI(30) were not significantly modified during pregnancy whereas MCF, CA(5) and CA(15) (INTEM, EXTEM, FIBTEM) increased significantly between the second and third trimesters (e.g. median [interquartile range]: MCF-FIBTEM, 13 [11-16] mm vs. 19 [17-23] mm, respectively, in controls and T3, p < 0.001). EXTEM values were not significantly different from those measured with APTEM. There were significant correlations between the results obtained with ROTEM and those from standard coagulation tests. ROTEM analysis showed a marked increase in coagulability during normal pregnancy. ROTEM values may serve as the basis for future studies in pregnant women.

Sentinel lymph node biopsy validation for large tumors.

BACKGROUND: Sentinel lymph node biopsy (SLNB) remains under discussion for large size tumors. The aim of this work has been to study the false negative rate (FNR) of SLNB for large tumors and predictive factors of false negative (FN). MATERIALS AND METHODS: A study of a multicentric cohort, involved patients presenting N0 breast cancer with a SLNB eventually completed by complementary axillary lymph node dissection (cALND). The main criteria were the FNR and the predictive factors of FN. RESULTS: 12.415 patients were included: 748 with tumors ≥30 mm, 1101 with tumors >20 and < 30 mm and 10.566 with tumors ≤20 mm, with a cALND respectively for 501 patients (67%), 523 (62.1%) and 2775 (26.3%). The FNR were respectively: 3.05% (IC95%: 1.3-4.8) for tumors ≥30 mm*, 3.5% (1.8-5.2) for tumors >20 and < 30 mm*, 1.8% (1-2.4) for tumors ≤20 mm (p < 0.05) (*Not significant). At multivariate analysis, SN number harvested ≤2 (OR:2.0, p = 0.023) and tumor size >20 and < 30 mm (OR:2.07, p = 0.017) were significant predictive factors of FN, without significant value for tumor size ≥30 mm (OR:1.83, p = 0.073). CONCLUSION: The FNR of SLNB was not higher amongst large size tumors compared to tumors of a smaller size. These results support the validation of SNLB for tumors up to 50 mm.

[Metastatic screening before adjuvant chemotherapy in breast cancer]. / Intérêt du bilan d'extension dans le cancer du sein avant chimiothérapie adjuvante.

INTRODUCTION: Systematic metastasis staging in early breast cancer is no longer recommended. However, it is still performed before adjuvant chemotherapy. MATERIALS AND METHODS: We assessed metastasis screening of asymptomatic women with a local breast cancer without lymph node involvement when adjuvant chemotherapy was indicated. The screening result was classified in 3 groups: "non-metastatic", "metastatic" and "suspect". For suspect screening, we analyzed the checking period and the consequences on cares. RESULTS: Out of 1545 patients with possible indication of chemotherapy, 690 indications of chemotherapy were validated by multidisciplinary meeting. Six hundred and thirty-nine metastasis screening were done. Five hundred and fifty-five screenings (86.9 %) were "non-metastatic", 3 screenings (0.5 %) were "metastatic" and 81 screenings (12.7 %) were "suspect". Out of this 81 suspect screening, only 47 screening have been checked, using 61 further investigations. No breast cancer metastasis was finally identified. CONCLUSION: Low rate of metastasis suggest reassessing metastasis screening before adjuvant chemotherapy for patients without lymph node involvement.

Quality of life of surgical oncology residents and fellows across Europe.

BACKGROUND: Data are currently lacking regarding the quality of life of surgical oncology (SO) trainees. We sought to assess the training conditions and quality of life of SO residents and fellows across Europe. MATERIAL AND METHODS: Members of the European Society for Surgical Oncology were invited to complete a Web-based survey that included a questionnaire specifically designed for SO trainees. Demographics, timing, and incentive to choose for SO, quality of life, and symptoms of fatigue, sleepiness, depression, and burnout, as well as self-reported medical errors, were assessed using validated instruments. RESULTS: The survey was completed by 109 residents and 53 fellows (mean age 34.6 ± 8.2). The mean Linear Analog Scale Assessment score for quality of life was 34.8 ± 8.6 out of a possible 50. A low level of fatigue was declared by 60% of the trainees. However, 44% scored an abnormal Epworth Sleepiness score, which was mostly related to in-hospital work time and lack of educational programs. High positive screenings regarding depression (51%) and burnout (25%) were associated with resident status and lack of mentorship, respectively. Major medical errors during the last 3 months were self-reported by 20% of the trainees. CONCLUSIONS: In Europe, the perceived quality of life is overall acceptable among trainees in SO. However, the present study demonstrated a high level of sleepiness, depression, and burnout symptoms. Additional work is required to identify and overcome the underlying causes of these symptoms.

[Insights of young French surgical oncologists: motives and training]. / Formation des jeunes chirurgiens inscrits en DESC de cancérologie option II--traitement chirurgical des tumeurs.

INTRODUCTION: In France, surgical oncology is not recognized as a unique specialty, but as a sub-specialization offered to surgeons in training. To date, their motives and training have not been studied. MATERIALS AND METHODS: We set a dedicated online survey suggested to 102 surgeons applying for the specific national degree in surgical oncology. RESULTS: The answer rate was 60%. Responders were constituted of a majority of male (61%), their median age was 31 years. They were mainly residents (33%) and fellows working in university (25%) or non-university (28%) hospitals. Most responders have chosen their organ specialization at the beginning, and their oncologic sub-specialization at the middle of their residency, after a meeting with a senior surgeon. Regarding practical education, 85% used surgical videos, 62% mechanical training devices, 60% animal surgery, and 38% cadaver dissection. Regarding career expectations, 67% would like to work in a cancer centre, 51% in a university hospital, and 26% in a private institution. To explain these choices, 51% referred to research and 65% to teaching interests. CONCLUSION: This study outlines the role of mentorship and the lack of practical teaching outside the operating room during the training in surgical oncology in France.

[Adjuvant treatments in breast cancer: interest of completion of axillary dissection in case of micrometastases or isolated tumor cells in sentinel lymph node]. / Traitements adjuvants dans le cancer du sein : impact du résultat du curage axillaire en cas de micrométastase ou de cellules tumorales isolées dans le ganglion sentinelle.

Prognostic signification of micrometastases ou isolated tumor cells (ITC) has not yet been clearly precised. Management of the axilla in case of micrometastases or ITC depends on the local pratices: no surgical completion or axillary lymph node dissection (ALND). Axillary lymph node status is the most important prognostic factor in patients with breast cancer; morbidity of ALND is now well known whereas its therapeutic benefit has not been demonstrated. This study is based on a retrospective database of 1375 patients who underwent sentinel node (SN) biopsy for breast cancer. In case of micrometastase or ITC in SN with completion axillary dissection, we examined if non-sentinel lymph node status has changed the indications of adjuvant treatments (chimiotherapy or radiotherapy). The results of our study show that non-sentinel lymph node status modify systemic therapy for a very few patients (less than 4% concerning chimiotherapy and less than 15% concerning radiotherapy).

New developments in treatment of ovarian carcinoma: focus on trabectedin.

Trabectedin is a new marine-derived compound that binds the DNA minor groove and interacts with proteins of the DNA repair machinery. Trabectedin has shown promising single-agent activity in pretreated patients with soft tissue sarcoma, and ovarian and breast cancer, and combination with various other chemotherapeutic drugs seems feasible. Toxicities are mainly hematologic and hepatic, with Grade 3-4 neutropenia and thrombocytopenia observed in approximately 50% and 20% of patients, respectively, and Grade 3-4 elevation of liver enzymes observed in 35%-50% of patients treated with trabectedin. The recently reported results of a large Phase III trial comparing pegylated liposomal doxorubicin (PLD) alone with a combination of PLD and trabectedin in patients with recurrent ovarian cancer showed improved progression-free survival with the combination of trabectedin and PLD, albeit at the price of increased toxicity. Current research focuses on the identification of predictive factors for patients treated with trabectedin, as well as the development of other combinations.

Síndrome de tako-tsubo probablemente asociado con la administración de sulprostona tras una cesárea / Tako-tsubo cardiomyopathy probably associated with administration of sulprostone following cesarean delivery

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