Frédéric Marchal

Complete Cytoreductive Surgery Plus Intraperitoneal Chemohyperthermia With Oxaliplatin for Peritoneal Carcinomatosis of Colorectal Origin

PURPOSE To compare the long-term survival of patients with isolated and resectable peritoneal carcinomatosis (PC) in comparable groups of patients treated with systemic chemotherapy containing oxaliplatin or irinotecan or by cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC). PATIENTS AND METHODS All patients with gross PC from colorectal adenocarcinoma who had undergone cytoreductive surgery plus HIPEC from 1998 to 2003 were evaluated. The standard group was constituted by selecting patients with colorectal PC treated with palliative chemotherapy during the same period, but who had not benefited from HIPEC because the technique was unavailable in the center at that time. RESULTS Forty-eight patients were retrospectively included in the standard group and were compared with 48 patients who had undergone HIPEC and were evaluated prospectively. All characteristics were comparable except age and tumor differentiation. There was no difference in systemic chemotherapy, with a mean of 2.3 lines per patient. Median follow-up was 95.7 months in the standard group versus 63 months in the HIPEC group. Two-year and 5-year overall survival rates were 81% and 51% for the HIPEC group, respectively, and 65% and 13% for the standard group, respectively. Median survival was 23.9 months in the standard group versus 62.7 months in the HIPEC group (P < .05, log-rank test). CONCLUSION Patients with isolated, resectable PC achieve a median survival of 24 months with modern chemotherapies, but only surgical cytoreduction plus HIPEC is able to prolong median survival to roughly 63 months, with a 5-year survival rate of 51%.

Cadmium-Free CuInS2/ZnS Quantum Dots for Sentinel Lymph Node Imaging with Reduced Toxicity

Semiconductor quantum dots (QDs) could significantly impact the performance of biomedical near-infrared (NIR) imaging by providing fluorescent probes that are brighter and more photostable than conventional organic dyes. However, the toxicity of the components of NIR emitting II-VI and IV-VI QDs that have been made so far (Cd, Hg, Te, Pb, etc.) has remained a major obstacle to the clinical use of QDs. Here, we present the synthesis of CuInS(2)/ZnS core/shell QDs emitting in the NIR ( approximately 800 nm) with good quantum yield and stability even after transfer into water. We demonstrate the potential of these QDs by imaging two regional lymph nodes (LNs) in vivo in mice. We then compare the inflammatory response of the axillary LN induced by different doses of CuInS(2)/ZnS and CdTeSe/CdZnS QDs and show a clear difference in acute local toxicity, the onset of inflammation only occurring at a 10 times more concentrated dose for CuInS(2)/ZnS QDs than for their Cd-containing counterparts.

Comparison of models to predict nonsentinel lymph node status in breast cancer patients with metastatic sentinel lymph nodes: a prospective multicenter study.

PURPOSE Several models have been developed to predict nonsentinel lymph node (non-SN) status in patients with breast cancer with sentinel lymph node (SN) metastasis. The purpose of our investigation was to compare available models in a prospective, multicenter study. PATIENTS AND METHODS In a cohort of 561 positive-SN patients who underwent axillary lymph node dissection, we evaluated the areas under the receiver operating characteristic curves (AUCs), calibration, rates of false negatives (FN), and number of patients in the group at low risk for non-SN calculated from nine models. We also evaluated these parameters in the subgroup of patients with micrometastasis or isolated tumor cells (ITC) in the SN. RESULTS At least one non-SN was metastatic in 147 patients (26.2%). Only two of nine models had an AUC greater than 0.75. Three models were well calibrated. Two models yielded an FN rate less than 5%. Three models were able to assign more than a third of patients in the low-risk group. Overall, the Memorial Sloan-Kettering Cancer Center nomogram and Tenon score outperform other methods for all patients, including the subgroup of patients with only SN micrometastases or ITC. CONCLUSION Our study suggests that all models do not perform equally, especially for the subgroup of patients with only micrometastasis or ITC in the SN. We point out available evaluation methods to assess their performance and provide guidance for clinical practice.

Peritoneal carcinomatosis treated with cytoreductive surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for advanced ovarian carcinoma: a French multicentre retrospective cohort study of 566 patients.

BACKGROUND Despite a high response rate to front-line therapy, prognosis of epithelial ovarian carcinoma (EOC) remains poor. Approaches that combine Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) have been developed recently. The purpose of this study was to assess early and long-term survival in patients treated with this strategy. PATIENTS AND METHODS A retrospective cohort multicentric study from French centres was performed. All consecutive patients with advanced and recurrent EOC treated with CRS and HIPEC were included. RESULTS The study included 566 patients from 13 centres who underwent 607 procedures between 1991 and 2010. There were 92 patients with advanced EOC (first-line treatment), and 474 patients with recurrent EOC. A complete cytoreductive surgery was performed in 74.9% of patients. Mortality and grades 3 to 4 morbidity rates were 0.8% and 31.3%, respectively. The median overall survivals were 35.4 months and 45.7 months for advanced and recurrent EOC, respectively. There was no significant difference in overall survival between patients with chemosensitive and with chemoresistant recurrence. Peritoneal Cancer Index (PCI) that evaluated disease extent was the strongest independent prognostic factor for overall and disease-free survival in all groups. CONCLUSION For advanced and recurrent EOC, curative therapeutic approach combining optimal CRS and HIPEC should be considered as it may achieve long-term survival in patients with a severe prognosis disease, even in patients with chemoresistant disease. PCI should be used for patients selection.

Design of new quantum dot materials for deep tissue infrared imaging

Near infrared fluorescence offers several advantages for tissue and in vivo imaging thanks to deeper photon penetration. In this article, we review a promising class of near infrared emitting probes based on semiconductor quantum dots (QDs), which have the potential to considerably improve in vivo fluorescence imaging thanks to their high brightness and stability. We discuss in particular the different criteria to optimize the design of near infrared QDs. We present the recent developments in the synthesis of novel QD materials and their different in vivo imaging applications, including lymph node localization, vasculature imaging, tumor localization, as well as cell tracking and QD-based multimodal probes.

Telerobotic-assisted laparoscopic hysterectomy for benign and oncologic pathologies: initial clinical experience with 30 patients

BackgroundTelerobotic-assisted laparoscopic attempts to provide technological solutions to the inherent limitations of traditional laparoscopic surgery. The aim of this study is to report the first experience of two teams concerning telerobotic-assisted laparoscopic hysterectomy for benign and malignant pathologies.MethodsThis study included 14 patients at the University Hospital Saint Pierre of Brussels (Belgium) and 16 patients at the Cancer Center of Nancy (France) from September 1999 to July 2003.ResultsThe indications for surgery were uterine malignant diseases in 12 cases (stade I) (41%), and benign pathologies of the uterus in 18 cases (59%). Five postoperative complications (17%) occurred, none related to the robotic system.ConclusionRobotic surgery can be safely performed in gynecologic and gynecologic–oncologic surgery with no increase in complication rates. A significant advance is represented by the surgeon’s ergonomic improvement.

Quantum dots in axillary lymph node mapping: Biodistribution study in healthy mice

BackgroundBreast cancer is the first cause of cancer death among women and its incidence doubled in the last two decades. Several approaches for the treatment of these cancers have been developed. The axillary lymph node dissection (ALND) leads to numerous morbidity complications and is now advantageously replaced by the dissection and the biopsy of the sentinel lymph node. Although this approach has strong advantages, it has its own limitations which are manipulation of radioactive products and possible anaphylactic reactions to the dye. As recently proposed, these limitations could in principle be by-passed if semiconductor nanoparticles (quantum dots or QDs) were used as fluorescent contrast agents for the in vivo imaging of SLN. QDs are fluorescent nanoparticles with unique optical properties like strong resistance to photobleaching, size dependent emission wavelength, large molar extinction coefficient, and good quantum yield.MethodsCdSe/ZnS core/shell QDs emitting around 655 nm were used in our studies. 20 μL of 1 μM (20 pmol) QDs solution were injected subcutaneously in the anterior paw of healthy nude mice and the axillary lymph node (ALN) was identified visually after injection of a blue dye. In vivo fluorescence spectroscopy was performed on ALN before the mice were sacrificed at 5, 15, 30, 60 min and 24 h after QDs injection. ALN and all other organs were removed, cryosectioned and observed in fluorescence microscopy. The organs were then chemically made soluble to extract QDs. Plasmatic, urinary and fecal fluorescence levels were measured.ResultsQDs were detected in ALN as soon as 5 min and up to 24 h after the injection. The maximum amount of QDs in the ALN was detected 60 min after the injection and corresponds to 2.42% of the injected dose. Most of the injected QDs remained at the injection site. No QDs were detected in other tissues, plasma, urine and feces.ConclusionEffective and rapid (few minutes) detection of sentinel lymph node using fluorescent imaging of quantum dots was demonstrated. This work was done using very low doses of injected QDs and the detection was done using a minimally invasive method.

Validation of the Tenon breast cancer score for predicting non-sentinel lymph node status in breast cancer patients with sentinel lymph node metastasis: a prospective multicenter study

Background Axillary lymph node dissection (ALND) is the standard treatment for patients with sentinel node (SN) metastasis, but most of these patients have negative non-sentinel nodes (non-SN). We have developed a scoring system (the Tenon score) to help identify a subgroup of patients who have a low risk of having non-SN metastases and who may thus forgo ALND. Here we validated the Tenon score in an independent cohort of SN-positive patients. Patients and methods We tested the accuracy of the Tenon score for predicting non-SN status in a prospective multicenter study of 226 SN-positive breast cancer patients. We calculated the false-negative rate, sensitivity, specificity, and positive (PPV) and negative predictive values (NPV). Receiver operating characteristics (ROC) curves were constructed and the areas under the curve (AUC) were calculated as a measure of discriminatory capacity. Results At least one non-SN was positive in 63 patients (27.9%). One hundred and twenty (53.1%) of the 226 patients had a Tenon score of 3.5 or less. Among these 120 patients, five had at least one positive non-SN. With a score cut-off of 3.5, the negative predictive value was 95.8% and the false-negative rate was 4.2%. Overall, the Tenon score accurately predicted non-SN status, with an AUC of 0.82 (95% confidence interval, 0.77–0.88). Conclusion In this multicenter study of an independent patient population, the Tenon score was accurate and reproducible for predicting non-SN status in breast cancer patients. The simplicity and reliability of the variables on which the Tenon score is based may be an advantage over other scoring systems.

Quality of Life in Patients with Oesophageal and Gastric Cancer: An Overview

An accurate assessment of health-related quality of life (QoL) in patients with oesophageal or gastric cancer (OGC) is essential to inform clinical decisions by providing insights into patients’ experiences of the impact of the disease and its treatments on physical, social and emotional health. Robust QoL questionnaires have been developed and validated in the past decade to measure the QoL of OGC patients. Baseline QoL variables are also prognostic for survival in patients with oesophageal cancer or metastatic gastric cancer. This article reviews the impact of surgery and reconstructive techniques, as well as of adjuvant and palliative treatments on the QoL of patients with OGC.

Hyperthermic intra-peritoneal chemotherapy using Oxaliplatin as consolidation therapy for advanced epithelial ovarian carcinoma. Results of a phase II prospective multicentre trial. CHIPOVAC study

INTRODUCTION The aim of the present study was to prospectively evaluate morbidity of intra-peritoneal hyperthermic chemotherapy (HIPEC) using Oxaliplatin as consolidation therapy for advanced epithelial ovarian carcinoma and, secondly, to study peritoneal recurrence. METHODS Between 2004 and 2007, 31 patients from 18 to 65 years with FIGO stage IIIC epithelial ovarian carcinoma were treated by surgery and a total of 6 cycles of platinum based chemotherapy. Those patients were eligible for consolidation therapy. We performed a second look laparotomy operation with intra-peritoneal hyperthermic chemotherapy. We used Oxaliplatin 460 mg/m(2) with 2 l/m(2) of dextrose in an open medial laparotomy for a total of 30 min at a temperature of 42-44 degrees C. RESULTS The grade 3 morbidity rate was 29% (95 CI: 14-45%). Nine patients experienced a total of 13 exploratory laparotomies for intra-abdominal bleeding after HIPEC. Two-year disease free and overall survival were 27% and 67% respectively. As a result of this high level of morbidity the trial was closed. CONCLUSION Using intra-peritoneal Oxaliplatin associated with hyperthermia as consolidation therapy for advanced ovarian cancer results in a high risk of grade 3 morbidities with only a small benefit on survival.