Benefit of the addition of hormone therapy to neoadjuvant anthracycline-based chemotherapy for breast cancer: comparison of predicted and observed pCR.

INTRODUCTION: Neoadjuvant hormonal therapy is generally considered a valid option for hormone receptor positive breast cancer (BC) patients who are unfit for chemotherapy or surgery. AIMS: Whilst numerous studies analyzed efficacy of neoadjuvant chemotherapy (CT) or endocrine therapy (HT) alone in hormone receptor positive patients, there is a lack of research looking at the usefulness of a preoperative combinatorial approach of CT and HT in this patient subgroup. METHODS: Using a predictive model previously described in the literature, developed to analyze the probability of benefit from preoperative chemotherapy, we were able to compare pathological complete response (pCR) rates expected with the use of CT alone with the pCR rates reported in a population of 192 patients treated with the combination of tamoxifen plus anthracycline-based CT at Cremona Hospital between 2003 and 2006. RESULTS: Even with a relatively small patient population, this approach provided insightful information for the selection of hormone receptor positive BC patients most likely to benefit from the use of preoperative HT and CT in combination. Whilst no statistically significant benefit was obtained with the addition of tamoxifen to neoadjuvant chemotherapy in the entire population, or in any of the molecular stratification subgroups, the analysis of the calibration curve showed that a combinatorial approach may improve pCR in patients with luminal B tumors. More specific trials should be designed to confirm our initial results. CONCLUSION: To the best of our knowledge, this is the first report investigating the efficacy of the combination of CT and HT in the neoadjuvant treatment of hormone receptor positive BC.

Evidence for the use of robotically assisted surgery in gynecologic cancers.

PURPOSE OF REVIEW: Robotically assisted laparoscopy has been introduced in the armamentarium of gynaecologic oncology surgeons. A lot of studies compared robotic surgery and laparotomy when the real issue is to demonstrate the interest and added value of robotically assisted laparoscopy versus standard laparoscopy. In this review, we will describe the most meaningful indications and advantages of robotically assisted laparoscopy in gynaecologic oncology. RECENT FINDINGS: The learning curve for advanced procedures in robot-assisted laparoscopy is shorter and easier than with the standard laparoscopy, especially for beginners. In most of the series, operating time is longer with robot, but complication rates are often decreased, especially in obese patients with a conversion rate to laparotomy that is decreased compared with standard laparoscopy. Robot-assisted laparoscopy can be used for surgery of high-risk endometrial cancer, staging of early-ovarian cancer, and pelvic exenteration in case of recurrent malignancies. Furthermore, more recent robots allow performing sentinel node biopsy in endometrial or cervical cancer using fluorescence detection with indocyanine green. SUMMARY: The spreading of robotic surgery led to an enhancement of minimal invasive surgical approach in general, and to the development of new indications in gynaecologic oncology. The superiority of robot-assisted laparoscopy still has to be demonstrated with properly designed trials.

Contribution of lymphoscintigraphy to intraoperative sentinel lymph node detection in early cervical cancer: Analysis of the prospective multicenter SENTICOL cohort.

PURPOSE: To evaluate the contribution of preoperative lymphoscintigraphy to intraoperative lymphatic mapping (ILM) in early cervical cancer METHODS: We conducted an ancillary analysis of the multicenter prospective SENTICOL study in early cervical cancer. Radiocolloid was injected intracervically on the day before (long protocol) or morning of (short protocol) surgery, lymphoscintigraphy was performed, and the results of a centralized image review were communicated to the surgeons. ILM was performed on combined radioactivity/patent blue detection. Sentinel lymph nodes (SLNs) were electively sampled before routine bilateral pelvic lymphadenectomy by laparoscopy. RESULTS: Of 139 patients in the modified intention-to-diagnose analysis, 114 had centrally reviewed lymphoscintigrams, which showed 352 SLNs in 100 patients. Lymphoscintigraphy and ILM detection rates were 87.8% and 97.8%, respectively. Agreement between lymphoscintigraphy and ILM was low for the number of SLNs (κ=0.23; -0.04; 0.49) and bilateral SLNs (κ=0.36; 0.2; 0.52). No patient without SLNs by ILM had SLNs by lymphoscintigraphy. Lymphoscintigraphy identified substantial proportions of unusual drainage pathways. No patients with metastatic nodes had SLNs by lymphoscintigraphy but not by ILM in the relevant territory. In 1 of the 2 patients with false-negative SLN results, SLNs were bilateral by lymphoscintigraphy and unilateral by ILM. CONCLUSION: Although the detection rate was lower by lymphoscintigraphy than by ILM, the substantial proportions of SLNs in unusual territories provided valuable guidance for the surgical exploration. Awareness of the limited agreement between lymphoscintigraphic and surgical detection might help surgeons decrease the false-negative rate.

Feasibility and performance of lymphoscintigraphy in sentinel lymph node biopsy for early cervical cancer: results of the prospective multicenter SENTICOL study.

OBJECTIVE: To evaluate feasibility, SLN detection rate, and SLN location of lymphoscintigraphy in sentinel lymph node (SLN) biopsy for early cervical cancer. METHODS: Ancillary analysis of data from the multicenter prospective SENTICOL study (January 2005-June 2007) of patients with early cervical cancer (FIGO stage IA with emboli to IB1) was conducted. Preoperative lymphoscintigraphy was performed after intracervical administration of 60 or 120 MBq of (99m)Tc-labeled radiocolloid on the day before (long protocol) or morning of (short protocol) surgery. SLNs were identified intraoperatively using combined radioactivity/patent blue detection. SLNs were sampled electively and routine bilateral pelvic lymphadenectomy was performed by laparoscopy. A centralized review of lymphoscintigraphies was performed to assess feasibility, detection rates, and anatomic SLN location. RESULTS: Of 139 patients included in the SENTICOL study, 133 received radiocolloid injection, and 131 (98.5 %) underwent preoperative lymphoscintigraphy, with the long protocol in three-fourths of cases. The lymphoscintigraphic detection rate was 87.8 %, with a median of 2 (1-4) SLNs per patient. By multivariate analysis, factors independently associated with lymphoscintigraphic SLN detection were age [odds ratio (OR) 0.91, 95 % confidence interval (95 % CI) 0.87-0.96; P < 0.001], and protocol (long vs. short; OR 8.23, 95 % CI 1.87-36.25; P = 0.005). Bilateral SLN identification by lymphoscintigraphy occurred in 67 % of cases and was independently influenced by age (OR 0.95, 95 % CI 0.92-0.98, P < 0.001) and protocol (OR 5.42, 95 % CI 2.21-13.27; P < 0.001). Although 60.5 % of preoperative SLNs were in the external iliac territory, unusual drainage patterns included the common iliac (19.6 %), para-aortic (10.8 %), and parametrial (6 %) basins. CONCLUSIONS: Our study demonstrates the feasibility and good detection rate of preoperative lymphoscintigraphy, with better detection in younger patients and with the long protocol. The high proportion of SLN basins in unexpected territories is of interest to guide intraoperative detection. Further studies are needed to better evaluate preoperative detection and to assess the contribution of lymphoscintigraphy to intraoperative detection.

Expression of somatostatin type-2 and -4 receptor and correlation with histological type in breast cancer.

BACKGROUND: Somatostatin is produced by hypothalamic cells and also by tumors. We were interested to evaluate the somatostatin type 2 (SSTR2) and type 4 (SSTR4) receptor expression on a large sample cohort of breast cancer cases. MATERIALS AND METHODS: We used two different Tissue Micro Arrays (TMA) to evaluate SSTR2 and SSTR4 distribution. We evaluated the correlation between SSTR2 and SSTR4 expression and 18 tumor cells markers. We also assessed SSTR mRNA expression on an independent breast cancer population and correlated levels of SSTR2 and SSTR4 expression to molecular breast cancer subtypes. RESULTS: 268 tumors were analyzed. The tumor overexpression of estrogen receptor was significantly correlated to the expression of SSTR2 (p=0.05) and SSTR4 (p=0.04). On principal component analysis, SSTR2 subtype characterized the luminal tumor type. On an independent breast cancer population, expression of SSTR2 and SSTR4 are independent from Human Epidermal Growth Factor Receptor 2 (Her2) and correlated with luminal tumors. CONCLUSION: Expression of somatostatin receptors is a marker of luminal breast tumors.

Robot-assisted laparoscopy for infertility treatment: current views.

To determine the interest of using robotic laparoscopic surgery in the management of female infertility, we reviewed our own activity and searched the Medline database for publications on robotic technology in infertility surgery, with the use of the following search words: robotic laparoscopy, tubal anastomosis, myomectomy, deep infiltrating endometriosis, and adnexal surgery. Robot-assisted laparoscopic surgery has seen rapid progression over the past few years. It has been mostly used for myomectomy, proximal tubal reanastomosis, and deep endometriosis surgery. Despite its increased range of indications, no randomized control studies are available. The place of robotic surgery in the management of infertility remains undetermined.

Correlation of immunohistopathological expression of somatostatin receptor-2 in breast cancer and tumor detection with 68Ga-DOTATOC and 18F-FDG PET imaging in an animal model.

BACKGROUND: Fludeoxyglucose positron emission topography ((18)F-FDG PET) is insufficiently sensitive at detecting small or low-grade breast tumors. The characterization of somatostatin receptors (SSTR) in tumors and the development of (68)Ga-DOTATOC PET for imaging could be of interest. The aim of this study was to validate an animal model expressing SSTR2 and to correlate the immunohistochemical (IHC) analysis with (18)F-FDG and (68)Ga-DOTATOC uptake in vivo. MATERIALS AND METHODS: Ten nude mice were xenografted with the ZR-75-1 breast tumor cell line. Imaging was performed with (68)Ga-DOTATOC and (18)F-FDG and correlated to IHC analysis of SSTR2. RESULTS: IHC analyses showed that the tumors expressed SSTR2. On PET imaging, the tumors were barely visible with (18)F-FDG, whereas with (68)Ga-DOTATOC, specific two-fold higher uptake was observed (p<0.005). CONCLUSION: Our results suggest that (68)Ga-DOTATOC PET could be used for detection of breast tumors not detected with (18)F-FDG. SSTR2 status should be assessed to allow for individual treatment.

Accuracy of diagnosis on CT scan of Surgicel® Fibrillar: results of a prospective blind reading study.

OBJECTIVE: Oxidized regenerated cellulose is a hemostatic agent used in surgery to control bleeding. Some case reports have suggested that it could lead to a mistaken diagnosis of abscess on postoperative CT scan. The objective of this study was to evaluate the diagnostic accuracy of CT scan for Surgicel® Fibrillar. STUDY DESIGN: We prospectively registered all patients who had Surgicel® Fibrillar left in the operative site during one year. Patients who had a CT scan for medical reasons (e.g. fever, pain, or occlusive syndrome) were evaluated and we compared the radiologists' conclusions with or without information about the use of Surgicel® (two different radiologists, one blinded to the use of Surgicel®). RESULTS: 18 patients who underwent pelvic laparotomy had Surgicel® Fibrillar left in the operative site. On first interpretation, the radiologist's conclusion was an abscess in 11% of cases, hematoma in 28%, collections with hydro-aeric levels in 33%, lymphocele in 6% and no conclusion in 11% of cases. For only 2 patients (11%) was the conclusion Surgicel® Fibrillar. After second interpretation by a radiologist aware of the presence of Surgicel® Fibrillar, Surgicel® Fibrillar was the main conclusion on 15 CT scans (83%). CONCLUSION: Oxidized regenerated cellulose is a differential diagnosis for abscess or collection. The radiologist should be informed about its presence to increase appropriate evaluation of CT scans and avoid inappropriate treatment.

Comparison of two nomograms to predict pathologic complete responses to neoadjuvant chemotherapy for breast cancer: evidence that HER2-positive tumors need specific predictors.

The aim of this study is to compare two published nomograms, the "Institut Gustave Roussy/M.D. Anderson Cancer Center" (IGR/MDACC) and the Colleoni nomograms, in predicting pathologic complete responses (pCR) to preoperative chemotherapy in an independent cohort and to assess the impact of HER2 status. Data from 200 patients with breast carcinoma treated with preoperative chemotherapy were collected. We calculated pCR rate predictions with the two nomograms and compared the predictions with the outcomes. Sixty percent of the patients with HER2-positive tumors received trastuzumab concomitantly with taxanes. Model performances were quantified with respect to discrimination and calibration. In the whole population, the area under the ROC curve (AUC) for the IGR/MDACC nomogram and the Colleoni nomogram were 0.74 and 0.75, respectively. Both of them underestimated the pCR rate (P = 0.026 and 0.0005). When patients treated with trastuzumab were excluded, the AUC were excellent: 0.78 for both nomograms with no significant difference between the predicted and the observed pCR (P = 0.14 and 0.15). When the specific population treated with trastuzumab preoperatively was analyzed, the AUC for the IGR/MDACC nomogram and the Colleoni nomogram were poor, 0.52 and 0.53, respectively. The IGR/MDACC and the Colleoni nomograms were accurate in predicting the probability of pCR after preoperative chemotherapy in the HER2-negative population but did not correctly predict pCR in the HER2-positive patients who received trastuzumab. This suggests that responses to preoperative chemotherapy, including trastuzumab, are biologically driven and that a specific nomogram or predictor for HER2-positive patients has to be developed.

[Somatostatin in breast cancer]. / La somatostatine dans le cancer du sein.

In man, somatostatin is a hormone mostly produced by hypothalamus. It plays different parts in hormonal regulation through many specific receptors in human body. It has also two interesting actions such as an anti-secretory activity, mostly on the gastrointestinal system and an antiproliferative action on tumor cells. Many synthetic somatostatin analogues, more stable than the natural one, have been developed and are already used in digestive surgery to treat postoperative digestive fistula. Also, the development of specific polyclonal antibodies allowed the identification of five specific somatostatin receptors and their localization in different cell species. The presence of the five receptors in breast cancer cells has than been demonstrated. The purpose of this literature review is to clarify the potential antitumor effect of somatastatin analogues in breast cancer; its use as a preventive agent on lymphorrhea after breast surgery and its employment in imaging for early breast cancer detection.