Targeting of 3D oral cancer spheroids by αVß6 integrin using near-infrared peptide-conjugated IRDye 680.

BACKGROUND: In the treatment of oral cavity cancer, margin status is one of the most critical prognostic factors. Positive margins are associated with higher local recurrence and lower survival rates. Therefore, the universal goal of oral surgical oncology is to achieve microscopically clear margins. Near-infrared fluorescence guided surgery (FGS) could improve surgical resection using fluorescent probes. αVß6 integrin has shown great potential for cancer targeting due to its overexpression in oral cancers. Red fluorescent contrast agent IRDye 680 coupled with anti-αVß6 peptide (IRDye-A20) represents an asset to improve FGS of oral cancer. This study investigates the potential of IRDye-A20 as a selective imaging agent in 3D three-dimensional tongue cancer cells. METHODS: αVß6 integrin expression was evaluated by RT-qPCR and Western Blotting in 2D HSC-3 human tongue cancer cells and MRC-5 human fibroblasts. Targeting ability of IRDye-A20 was studied in both cell lines by flow cytometry technique. 3D tumor spheroid models, homotypic (HSC-3) and stroma-enriched heterotypic (HSC-3/MRC-5) spheroids were produced by liquid overlay procedure and further characterized using (immuno)histological and fluorescence-based techniques. IRDye-A20 selectivity was evaluated in each type of spheroids and each cell population. RESULTS: αVß6 integrin was overexpressed in 2D HSC-3 cancer cells but not in MRC-5 fibroblasts and consistently, only HSC-3 were labelled with IRDye-A20. Round shaped spheroids with an average diameter of 400 µm were produced with a final ratio of 55%/45% between HSC-3 and MRC-5 cells, respectively. Immunofluorescence experiments demonstrated an uniform expression of αVß6 integrin in homotypic spheroid, while its expression was restricted to cancer cells only in heterotypic spheroid. In stroma-enriched 3D model, Cytokeratin 19 and E-cadherin were expressed only by cancer cells while vimentin and fibronectin were expressed by fibroblasts. Using flow cytometry, we demonstrated that IRDye-A20 labeled the whole homotypic spheroid, while in the heterotypic model all cancer cells were highly fluorescent, with a negligible fluorescence in fibroblasts. CONCLUSIONS: The present study demonstrated an efficient selective targeting of A20FMDV2-conjugated IRDye 680 in 3D tongue cancer cells stroma-enriched spheroids. Thus, IRDye-A20 could be a promising candidate for the future development of the fluorescence-guided surgery of oral cancers.

[Surgery or not on an atypical breast lesion? Taking anxiety into account in shared decision support from a prospective cohort of 300 patients]. / Opérer ou non une lésion atypique du sein ? Prise en compte de l'anxiété dans l'aide à la décision partagée à partir d'une cohorte prospective de 300 patientes.

INTRODUCTION: Organized and individual breast screening have been accompanied by an increase in the detection of "atypical breast lesions (ABL)". Recently, the NOMAT multicenter study proposed a predictive model of the risk of developing breast cancer after detection of an ABL in order to avoid surgical removal of "low-risk" lesions. It also aimed to provide information on psychological experience, in particularly anxiety, to assist in the shared medical decision process. METHODS: Three hundred women undergoing surgery for ABL were included between 2015 and 2018 at 18 French centers. Women completed questionnaires before and after surgery assessing their level of anxiety (STAI-State, STAI-Trait), their level of tolerance to uncertainty, their perceived risk of developing a breast cancer, and their satisfaction with the management care. RESULTS: One hundred nighty nine patients completed the STAI-Status before and after surgery. Overall, a decrease in anxiety level (35.4 vs 42.7, P<0.001) was observed. Anxious temperament and greater intolerance to uncertainty were significantly associated swith decreased anxiety (33%), whereas younger age was associated with increased anxiety (8%). CONCLUSION: Surgery for ABL seems to be associated with only a few cases with an increase in anxiety and seems to increase the perception of the risk of developing breast cancer. Taking into account the psychological dimension remains in all cases essential in the process of shared therapeutic decision.

Prognosis of poorly cohesive gastric cancer after complete cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy (CYTO-CHIP study).

BACKGROUND: The incidence of gastric poorly cohesive carcinoma (PCC) is increasing. The prognosis for patients with peritoneal metastases remains poor and the role of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is controversial. The aim was to clarify the impact of gastric PCC with peritoneal metastases treated by CRS with or without HIPEC. METHODS: All patients with peritoneal metastases from gastric cancer treated with CRS with or without HIPEC, in 19 French centres, between 1989 and 2014, were identified from institutional databases. Clinicopathological characteristics and outcomes were compared between PCC and non-PCC subtypes, and the possible benefit of HIPEC was assessed. RESULTS: In total, 277 patients were included (188 PCC, 89 non-PCC). HIPEC was performed in 180 of 277 patients (65 per cent), including 124 of 188 with PCC (66 per cent). Median overall survival (OS) was 14.7 (95 per cent c.i. 12.7 to 17.3) months in the PCC group versus 21.2 (14.7 to 36.4) months in the non-PCC group (P < 0.001). In multivariable analyses, PCC (hazard ratio (HR) 1.51, 95 per cent c.i. 1.01 to 2.25; P = 0.044) was associated with poorer OS, as were pN3, Peritoneal Cancer Index (PCI), and resection with a completeness of cytoreduction score of 1, whereas HIPEC was associated with improved OS (HR 0.52; P < 0.001). The benefit of CRS-HIPEC over CRS alone was consistent, irrespective of histology, with a median OS of 16.7 versus 11.3 months (HR 0.60, 0.39 to 0.92; P = 0.018) in the PCC group, and 34.5 versus 14.3 months (HR 0.43, 0.25 to 0.75; P = 0.003) in the non-PCC group. Non-PCC and HIPEC were independently associated with improved recurrence-free survival and fewer peritoneal recurrences. In patients who underwent HIPEC, PCI values of below 7 and less than 13 were predictive of OS in PCC and non-PCC populations respectively. CONCLUSION: In selected patients, CRS-HIPEC offers acceptable outcomes among those with gastric PCC and long survival for patients without PCC.

[Survivorship care plan (SCP) : The viewpoints of women with breast cancer and their general practitioners]. / Programme personnalisé d'après cancer (PPAC) : vision des patientes atteintes de cancer du sein et de leur médecin traitant.

BACKGROUND: The French National Cancer Institute recommends the use of survivorship care plans (SCP) for all cancer survivors. Developing useful SCP's requires understanding of what survivors and their providers need and how SCP's can be implemented in practice. We conducted a study to assess the delivery of SCP comprehensive binders for breast cancer women (BCW) and their general practitioners (GP) in a Cancer center from January 2019. METHODS: SCP binders, containing a full range of information on topics related to post-cancer care to survivor-specific information and referrals, were given to BCW during a post-treatment dedicated consultation. Then a letter, containing the treatment summary and 5-year follow-up schedule, was sent to their GPs. Comprehensive binder delivery assessment was carried out using item checkbox, and anonymous open-answered, self-reported questionnaires were sent by email to BCW and their GPs. RESULTS: The questionnaire response rates were 81.3% for BCW (n = 109/134) and 48.6% for their GPs (n = 52/107). Most BCW (85%) reported that SCP binders provided useful and comprehensive information. However, some of them (18%) felt abandoned and anonymous during the post-treatment follow-up. Most GPs found SCP letters from our anti-cancer center physicians to be useful for their patients, 38% of them had used this information to assure transition of care with other care providers. In addition, GPs were unanimous to express their feeling that this SCP could improve the long-term surveillance of BCW. There was a high concordance between BCW survivors' and PCP' answers, especially regarding SCPs as a communication bridge between GPs and BCW survivors. Response results concerning use of the binders: to talk about them: 59% for BCW vs. 51% for GPs, and to show them: 35% for BCW vs. 31% for GPs. CONCLUSION: The opinions of BCW survivors' and PCP' opinions about the use of SCP's by our Cancer Center seems to be favourable. It is essential to implement and develop SCP's as a key tool in long-term surveillance and support for cancer patient survivors and they are a useful instrument for care providers in communication and transition.

Early and late morbidity of local excision after chemoradiotherapy for rectal cancer.

BACKGROUND: Local excision (LE) after chemoradiotherapy is a new option in low rectal cancer, but morbidity has never been compared prospectively with total mesorectal excision (TME). Early and late morbidity were compared in patients treated either by LE or TME after neoadjuvant chemoradiotherapy for rectal cancer. METHOD: This was a post-hoc analysis from a randomized trial. Patients with clinical T2/T3 low rectal cancer with good response to the chemoradiotherapy and having either LE, LE with eventual completion TME, or TME were considered. Early (1 month) and late (2 years) morbidities were compared between the three groups. RESULTS: There were no deaths following surgery in any of the three groups. Early surgical morbidity (20 per cent LE versus 36 per cent TME versus 43 per cent completion TME, P = 0.025) and late surgical morbidity (4 per cent versus 33 per cent versus 57 per cent, P < 0.001) were significantly lower in the LE group than in the TME or the completion TME group. of LE, was associated with the lowest rate of early (10 versus 18 versus 21 per cent, P = 0.217) and late medical morbidities (0 versus 7 versus 7 per cent, P = 0.154), although this did not represent a significant difference between the groups. The severity of overall morbidity was significantly lower at 2 years after LE compared with TME or completion TME (4 versus 28 versus 43 per cent grade 3-5, P < 0.001). CONCLUSION: The rate of surgical complications after neoadjuvant chemoradiotherapy in the LE group was half that of TME group at 1 month and 10 times lower at 2 years. LE is a safe approach for organ preservation and should be considered as an alternative to watch-and-wait in complete clinical responders and to TME in subcomplete responders.

[Comparing outcomes of Immediate Breast reconstruction with and without use of radiotherapy]. / Comparaison des résultats de reconstruction mammaire immédiate par prothèse avec et sans radiothérapie.

BACKGROUND: Breast cancer and its treatment remains a public health problem. There is still a lack of epidemiological data concerning complications and aesthetic results bound to radiotherapy after an immediate breast reconstruction. The objective of this study was to compare outcomes of immediate breast reconstruction regardless to the use of radiotherapy (history of radiotherapy or adjuvant radiation therapy), in order to determine risk factor of complications and bad aesthetic results. METHODS: We conducted a retrospective study between January 2014 and December 2016 at the hospital "Gustave Roussy" in Paris, concerning breast cancer patients who needed immediate breast reconstruction after total mastectomy. The primary endpoint was to assess the failure rate of reconstruction and the aesthetic result, the secondary endpoint assessed the early and late rate of complications. We realized a multivariate analysis in order to identify risks factors that may predict complications. RESULTS: Three hundred and thirty three patients have been included: 157 in the "radiotherapy group" compared to 176 in the "no radiotherapy group". Preoperative characteristics were comparable. Average follow-up was between 1 and 3years without missing. Patients who benefited from radiotherapy had an equal risk failure of reconstruction. The subgroup analysis revealed non-significant differences: 12.7% failure rate reconstruction in the "radiotherapy group" vs. 12.5%. We could notify a better rate of "excellent results" in the "no radiotherapy group": 35% vs. 8.2%. Secondary outcomes were comparable. CONCLUSIONS: Radiotherapy related to immediate breast reconstruction didn't increase the failure rate of reconstruction or aesthetic results, comparatively to non-irradiated patients. It is therefore permissible to suggest an immediate breast reconstruction to any patients which would benefit from a total mastectomy followed by radiotherapy; in order to prevent them from a secondary breast reconstruction, who could be physically and psychologically more impactful.

Surgery in reference centers improves survival of sarcoma patients: a nationwide study.

BACKGROUND: NETSARC (netsarc.org) is a network of 26 sarcoma reference centers with specialized multidisciplinary tumor boards (MDTB) aiming to improve the outcome of sarcoma patients. Since 2010, presentation to an MDTB and expert pathological review are mandatory for sarcoma patients nationwide. In the present work, the impact of surgery in a reference center on the survival of sarcoma patients investigated using this national NETSARC registry. PATIENTS AND METHODS: Patients' characteristics and follow-up are prospectively collected and data monitored. Descriptive, uni- and multivariate analysis of prognostic factors were conducted in the entire series (N = 35 784) and in the subgroup of incident patient population (N = 29 497). RESULTS: Among the 35 784 patients, 155 different histological subtypes were reported. 4310 (11.6%) patients were metastatic at diagnosis. Previous cancer, previous radiotherapy, neurofibromatosis type 1 (NF1), and Li-Fraumeni syndrome were reported in 12.5%, 3.6%, 0.7%, and 0.1% of patients respectively. Among the 29 497 incident patients, 25 851 (87.6%) patients had surgical removal of the sarcoma, including 9949 (33.7%) operated in a NETSARC center. Location, grade, age, size, depth, histotypes, gender, NF1, and surgery outside a NETSARC center all correlated to overall survival (OS), local relapse free survival (LRFS), and event-free survival (EFS) in the incident patient population. NF1 history was one of the strongest adverse prognostic factors for LRFS, EFS, and OS. Presentation to an MDTB was associated with an improved LRFS and EFS, but was an adverse prognostic factor for OS if surgery was not carried out in a reference center. In multivariate analysis, surgery in a NETSARC center was positively correlated with LRFS, EFS, and OS [P < 0.001 for all, with a hazard ratio of 0.681 (95% CI 0.618-0.749) for OS]. CONCLUSION: This nationwide registry of sarcoma patients shows that surgical treatment in a reference center reduces the risk of relapse and death.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for pseudomyxoma peritonei of appendicular and extra-appendicular origin.

BACKGROUND: The prognostic value of the primary neoplasm responsible for pseudomyxoma peritonei (PMP) remains poorly studied. The aim of this study was to determine the prognosis for patients with extra-appendicular PMP (EA-PMP) treated optimally with complete cytoreductive surgery (CCRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: All patients treated for PMP with CCRS and HIPEC between 1994 and 2016 were selected retrospectively from a French multicentre database. Patients with EA-PMP had pathologically confirmed non-neoplastic appendices and were matched in a 1 : 4 ratio with patients treated for appendicular PMP (A-PMP), based on a propensity score. RESULTS: Some 726 patients were identified, of which 61 (EA-PMP group) were matched with 244 patients (A-PMP group). The origins of primary tumours in the EA-PMP group included the ovary (45 patients), colon (4), urachus (4), small bowel (1), pancreas (1) and unknown (6). The median peritoneal carcinomatosis index was comparable in EA-PMP and A-PMP groups (15·5 versus 18 respectively; P = 0·315). In-hospital mortality (3 versus 2·9 per cent; P = 1·000) and major morbidity 26 versus 25·0 per cent; P = 0·869) were also similar between the two groups. Median follow-up was 66·9 months. The 5-year overall survival rate was 87·8 (95 per cent c.i. 83·2 to 92·5) per cent in the A-PMP group and 87 (77 to 96) per cent in the EA-PMP group. The 5-year disease-free survival rate was 66·0 (58·7 to 73·4) per cent and 70 (53 to 83) per cent respectively. CONCLUSION: Overall and disease-free survival following treatment with CCRS and HIPEC is similar in patients with pseudomyxoma peritonei of appendicular or extra-appendicular origin.

Sialendoscopy for sialolithiasis in children: 4-8 years follow up.

Sialolithiasis is rare in children, there are no guidelines for its treatment, and there are few, if any, long term follow-up studies. We report a retrospective review of medical records of children who were treated for sialolithiasis by sialendoscopy between 1 January 2007 and 31 December 2011, and who have been followed up for 4-8 years. Personal and clinical details, including age, sex, symptoms, whether the lithiasis was parotid or submandibular, the technique of sialendoscopy and complications, were recorded. Twenty-six children (30 sides) were successfully treated by sialendoscopy between 2007 and 2011 (mean (range) age 12 (3-17) years). Stones were removed from the parotid gland in four patients and the submandibular gland in 22. The main indication for sialendoscopy was swelling of the salivary gland during meals. Twenty-six procedures were done endoscopically. Twelve were treated with a wire basket alone, 10 by the combined approach, and laser was used in eight. Four patients developed complications, but without long-term effects. During follow-up of 4-8 years there were no recurrent swellings. We conclude that endoscopic treatment of stones in childhood is an efficient and conservative option for salivary glands, has few complications and no clinical recurrence at medium to long-term follow-up.

Prospective Assessment of First-Year Quality of Life After Pelvic Exenteration for Gynecologic Malignancy: A French Multicentric Study.

BACKGROUND: Pelvic exenteration remains one of the most mutilating procedures, with important postoperative morbidity, an altered body image, and long-term physical and psychosocial concerns. This study aimed to assess quality of life (QOL) during the first year after pelvic exenteration for gynecologic malignancy performed with curative intent. METHODS: A French multicentric prospective study was performed by including patients who underwent pelvic exenteration. Quality of life by measurement of functional and symptom scales was assessed using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 (version 3.0) and the EORTC QLQ-OV28 questionnaires before surgery, at baseline, and 1, 3, 6, and 12 months after the procedure. RESULTS: The study enrolled 97 patients. Quality of life including physical, personal, fatigue, and anorexia reported in the QLQ-C30 was significantly reduced 1 month postoperatively and improved at least to baseline level 1 year after the procedure. Body image also was significantly reduced 1 month postoperatively. Global health, emotional, dyspnea, and anorexia items were significantly improved 1 year after surgery compared with baseline values. Unlike younger patients, elderly patients did not regain physical and social activities after pelvic exenteration. CONCLUSIONS: Therapeutic decision on performing a pelvic exenteration can have a severe and permanent impact on all aspects of patients' QOL. Deterioration of QOL was most significant during the first 3 months after surgery. Elderly patients were the only group of patients with permanent decreased physical and social function. Preoperative evaluation and postoperative follow-up evaluation should include health-related QOL instruments, counseling by a multidisciplinary team to cover all aspects concerning stoma care, sexual function, and long-term concerns after surgery.

Phase III study of the European Organisation for Research and Treatment of Cancer satisfaction with cancer care core questionnaire (EORTC PATSAT-C33) and specific complementary outpatient module (EORTC OUT-PATSAT7).

Advances in cancer care delivery require revision and further development of questionnaires assessing patients' perceived quality of care. This study pre-tested the revised EORTC satisfaction with cancer care core questionnaire applicable in both the cancer inpatient and outpatient settings, and its new, outpatient-specific complementary module. The process of revision, development of the extended application, and pre-testing of these questionnaires was based on phases I to III of the "EORTC Quality of Life Group Module Development Guidelines." In phase III, patients in 11 countries in four European regions, South America and Asia completed provisional versions of the questionnaires. Fifty-seven relevant issues selected from literature reviews and input from experts were operationalized into provisional items, and subsequently translated into ten languages. Assessment of understanding, acceptability, redundancy and relevance by patients (n = 151) from oncology inpatient wards, and outpatient chemotherapy, radiotherapy and consultation settings, led to retention of, deletion of and merging of 40, 14 and 6 items respectively. Cronbach's alpha coefficients for hypothesized questionnaire scales were above 0.80. Our results provide preliminary support for the 33-item EORTC Satisfaction with cancer care core questionnaire and the 7-item complementary module specific for the outpatient care setting. A large scale phase IV cross-cultural psychometric study is now underway.

Which Foetal-Pelvic Variables Are Useful for Predicting Caesarean Section and Instrumental Assistance?

OBJECTIVE: To assess the variables useful to predict caesarean delivery (CD) and instrumental assistance, through the analysis of a large number of foetal-pelvic variables, using discriminant analysis. MATERIALS AND METHODS: One hundred and fourteen pregnant women were included in this single-centre prospective study. For each mother-foetus pair, 43 pelvic and 18 foetal variables were measured. Partial least squares-discriminant analysis was performed to identify foetal-pelvic variables that could statistically separate the 3 delivery modality groups: spontaneous vaginal delivery (SVD), CD, and instrument-assisted delivery (IAD). RESULTS: For the SVD versus CD model, voluminous foetuses and women with a narrow pelvic inlet had a greater risk for requiring CD. The most efficient variables for discrimination were the transverse diameter and foetal weight. The antero-posterior inlet and obstetric conjugate were considered in this model, with the former being a useful variable but not the latter. For the SVD versus IAD model, the most important variables were the foetal variables, particularly the bi-parietal diameter. Women with a reduced antero-posterior outlet diameter and a narrow pubic arch were more at risk of requiring an IAD. CONCLUSION: The antero-posterior inlet was an efficient variable unlike the obstetric conjugate. The obstetric conjugate diameter should no longer be considered a useful variable in estimating the arrest of labour. Antero-posterior inlet diameter was a sagittal variable that should be taken into account. The comparison of sub-pubic angle and bi-parietal and antero-posterior outlet diameters was useful in identifying a risk of requiring instrumental assistance.

[The emergence of obstetrical mechanism: From Lucy to Homo sapiens]. / L'émergence de la mécanique obstétricale : de Lucy à Homo sapiens.

The evolutionary history of modern birth mechanism is now a renewed interest in obstetrical papers. The purpose of this work is to review the literature in paleo-obstetrical field. Our analysis focuses on paleo-obstetrical hypothesis, from 1960 to the present day, based on the reconstruction of fossil pelvis. Indeed, these pelvic reconstructions usually provide an opportunity to make an obstetrical assumption in our ancestors. In this analysis, we show that modern birth mechanism takes place during the emergence of our genus 2 million years ago. References are made to human specificities related to obstetrical mechanism: exclusive bipedalism, increase of brain size at birth, metabolic cost of the pregnancy and deep trophoblastic implantation.

Treatment of salivary stones by intraductal pneumatic lithotripsy: A preliminary presentation of the StoneBreaker with sterile bag covering.

INTRODUCTION: Sialendoscopy has changed the management of obstructive sialadenitis. Nowadays, minimally invasive techniques evolve to preserve salivary gland function. Intraductal lithotripsy allows stones fragmentation and retrieval without opening the salivary duct. We report our experience with the StoneBreaker (SB), a new lithotripter with improvement using a sterile bag that permits reuse of the SB without passing to sterilization. TECHNICAL NOTE: The non-sterilized SB was used into a sterile camera sleeve in 5 patients, 3 submandibular lithiases and 2 parotid lithiases. Technique and outcomes were described with a review of the literature. An explanatory video of the procedure was performed. DISCUSSION: Complete fragmentation was achieved and all fragments were extracted without any ductal damage. Utilization of the sterile sleeve did not change the SB efficiency and the procedure duration. The use of a sterile bag allowed several consecutive procedures with a single non-sterilized handpiece. However, the gas cartridge change may be more delicate when more than 80 impacts are needed. Patients remained symptoms and stones free one month after surgery.

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.

Results of a multicenter phase I dose-finding trial of hyperthermic intraperitoneal cisplatin after neoadjuvant chemotherapy and complete cytoreductive surgery and followed by maintenance bevacizumab in initially unresectable ovarian cancer.

PURPOSE: Hyperthermic intraperitoneal chemotherapy (HIPEC) may improve the outcome of patients with initially unresectable ovarian cancer who are eligible for complete cytoreductive surgery (CCRS) after neoadjuvant chemotherapy. The main objective of this multicenter phase-I study was to identify the recommended dose of cisplatin for HIPEC at CCRS after neoadjuvant carboplatin and paclitaxel (CP). METHODS: Patients were treated with 6cycles of CP followed by CCRS and HIPEC using cisplatin heated for one hour at 42°C+/-1°C. Four cisplatin dose-levels were evaluated: 50, 60, 70, 80mg/m(2). Dose-limiting toxicities (DLTs) were defined as a grade≥IIIb adverse event (Dindo classification). The Continual Reassessment Method was used for this dose-finding study, with a target percentage of DLT set at 20%. Twenty-two cycles (15mg/kg/cycle) of maintenance bevacizumab therapy were planned after surgery. RESULTS: Between June-2011 and September-2012, 30 patients were recruited. No DLT occurred at the first three dose-levels (4, 4 and 5 patients at 50, 60 and 70mg/m(2) respectively). At dose-level 4 (80mg/m(2), 17 patients), four DLTs occurred: renal failure (n=2), peritonitis (n=1) and hemorrhage (n=1). Eight weeks after surgery, creatinine clearance was reduced to <30mL/min in 3 patients, all treated at 80mg/m(2), and between 30 and 60mL/min in 6 patients (2, 1, 1 and 2 at the four dose-levels respectively). Twenty patients started maintenance bevacizumab, and 7 received the 22 courses initially planned. CONCLUSIONS: Based on the observed DLTs and prolonged impairment of renal function, we recommend a dose of 70mg/m(2) of cisplatin for HIPEC.

Classification of parotidectomies: a proposal of the European Salivary Gland Society.

The objective of this study is to provide a comprehensive classification system for parotidectomy operations. Data sources include Medline publications, author's experience, and consensus round table at the Third European Salivary Gland Society (ESGS) Meeting. The Medline database was searched with the term "parotidectomy" and "definition". The various definitions of parotidectomy procedures and parotid gland subdivisions extracted. Previous classification systems re-examined and a new classification proposed by a consensus. The ESGS proposes to subdivide the parotid parenchyma in five levels: I (lateral superior), II (lateral inferior), III (deep inferior), IV (deep superior), V (accessory). A new classification is proposed where the type of resection is divided into formal parotidectomy with facial nerve dissection and extracapsular dissection. Parotidectomies are further classified according to the levels removed, as well as the extra-parotid structures ablated. A new classification of parotidectomy procedures is proposed.

[Changing and follow-up of silicone gel-filled breast implants: Multicentric, retrospective study about 130 rupture cases]. / Surveillance et changement des implants mammaires en gel de silicone: étude rétrospective a propos de 130 cas de rupture d'implants.

SUBJECT: A recent report from "Agence Nationale de sécurité du medicament et des produits de santé" (ANSM) assesses the rupture of silicone gel breast implants without proposing rules for follow-up and replacement of implants. OBJECTIVE: To demonstrate that systematic follow-up surveillance of silicone breast implants could improve early diagnosis of ruptures; to propose a surveillance protocol based on the findings. MATERIALS AND METHODS: This is a multicentric, retrospective study which reports cases of ruptured silicone gel breast implants from January 2006 to June 2014. Using Case-notes from ANSM and quotations from CCAM certificates, 130cases were gathered from 6 centers. RESULTS: The average time between implantation and the diagnosis of ruptures was 9.24 years (± 6.19). Forty cases of ruptured implants (30.8%) originated from original reconstruction or symmetrisation in the context of a breast carcinoma; and 90 (69.2%) originated from augmentation mammaplasty. The average length in reconstructive group was 6.97 years (± 3.33). The difference in the lifetime of the implants between both groups was statistically significant (P = 0.0291). A clinical abnormality led to an imaging assessment in only 19.7% of cases; rupture was thus mainly discovered incidentally either during a systematic breast screening (59.8%), or during a preoperative examination for an aesthetic surgery (20.5%) (P = 0.0082). CONCLUSIONS: The results suggest that implant ruptures of silicone gel breast implants are under diagnosed. Clinical follow-up seems insufficient to diagnose implant ruptures. Ultra sound surveillance (± MRI) could be proposed 4 years, 7 years and 10 years after the initial surgery. It does not seem appropriate to propose a systematic change of implant without the incidence of a rupture.