The 2022 PSOGI International Consensus on HIPEC Regimens for Peritoneal Malignancies: Epithelial Ovarian Cancer.

BACKGROUND AND AIM: We report the results of an international consensus on hyperthermic intraperitoneal chemotherapy (HIPEC) regimens for epithelial ovarian cancer (EOC) performed with the following goals: To define the indications for HIPEC To identify the most suitable HIPEC regimens for each indication in EOC To identify areas of future research on HIPEC To provide recommendations for some aspects of perioperative care for HIPEC METHODS: The Delphi technique was used with two rounds of voting. There were three categories of questions: evidence-based recommendations [using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) system with the patient, intervention, comparator, and outcome (PICO) method], an opinion survey, and research recommendations. RESULTS: Seventy-three (67.5%) of 108 invited experts responded in round I, and 68 (62.9%) in round II. Consensus was achieved for 34/38 (94.7%) questions. However, a strong positive consensus that would lead to inclusion in routine care was reached for only 6/38 (15.7%) questions. HIPEC in addition to interval cytoreductive surgery (CRS) received a strong positive recommendation that merits inclusion in routine care. Single-agent cisplatin was the only drug recommended for routine care, and OVHIPEC-1 was the most preferred regimen. The panel recommended performing HIPEC for a minimum of 60 min with a recommended minimum intraabdominal temperature of 41°C. Nephroprotection with sodium thiosulfate should be used for cisplatin HIPEC. CONCLUSIONS: The results of this consensus should guide clinical decisions on indications of HIPEC and the choice and various parameters of HIPEC regimens and could fill current knowledge gaps. These outcomes should be the basis for designing future clinical trials on HIPEC in EOC.

"Chronic fatigue, quality of life and long-term side-effects of chemotherapy in patients treated for non-epithelial ovarian cancer: national case-control protocol study of the GINECO-Vivrovaire rare tumors INCa French network for rare malignant ovarian tumors".

BACKGROUND: Germ cell tumors and sex cord stromal tumors are rare cancers of the ovary. They mainly affect young women and are associated with a high survival rate. The standard treatment mainly involves conservative surgery combined with chemotherapy [bleomycin, etoposide and cisplatin (BEP)] depending on the stage and the prognostic factors, as for testicular cancers. As reported in testicular cancer survivors, chemotherapy may induce sequelae impacting quality of life, which has not yet been evaluated in survivors of germ cell tumors and sex cord stromal tumors. The GINECO-VIVROVAIRE-Rare tumor study is a two-step investigation aiming to assess i) chronic fatigue and quality of life and ii) long-term side-effects of chemotherapy with a focus on cardiovascular and pulmonary disorders. METHODS: Using self-reported questionnaires, chronic fatigue and quality of life are compared between 134 ovarian cancer survivors (cancer-free ≥2 years after treatment) treated with surgery and chemotherapy and 2 control groups (67 ovarian cancer survivors treated with surgery alone and 67 age-matched healthy women). Medical data are collected from patient records. In the second step evaluating the long-term side-effects of chemotherapy, a subgroup of 90 patients treated with chemotherapy and 45 controls undergo the following work-up: cardiovascular evaluation (clinical examination, non-invasive cardiovascular tests to explore heart disease, blood tests), pulmonary function testing, audiogram, metabolic and hormonal blood tests. Costs of sequelae will be also assessed. Patients are selected from the registry of the INCa French Network for Rare Malignant Ovarian Tumors, and healthy women by the 'Seintinelles' connected network (collaborative research platform). DISCUSSION: This study will provide important data on the potential long-term physical side-effects of chemotherapy in survivors of Germ Cell Tumors (GCT) and Sex Cord Stromal Tumors (SCST), especially cardiovascular and pulmonary disorders, and neurotoxicity. The identification of long-term side-effects can contribute to adjusting the treatment of ovarian GCT or SCST patients and to managing follow-up with adapted recommendations regarding practices and chemotherapy regimens, in order to reduce toxicity while maintaining efficacy. Based on the results, intervention strategies could be proposed to improve the management of these patients during their treatment and in the long term. TRIAL REGISTRATION: This trial was registered at clinicaltrials.gov : 03418844 , on 1 February 2018. This trial was registered on 25 October 2017 under the unique European identification number (ID-RCB): 2017-A03028-45. Recruitment Status: Recruiting. PROTOCOL VERSION: Version n° 4.2 dated from Feb 19, 2021. TRIAL SPONSOR: Centre François Baclesse, 3 avenue du Général Harris, F-14076 Caen cedex 05, France.

Development and validation of an LC-MS/MS method for the simultaneous determination of bisphenol A and its chlorinated derivatives in adipose tissue.

Bisphenol A (BPA) and its chlorinated derivatives (Clx-BPA) are environmental pollutants exhibiting endocrine-disrupting (ED) properties suspected to be involved in the pathogenesis of hormone-dependent cancers, such as breast and prostate cancers. Due to their lipophilic properties, they may accumulate in adipose tissue which could therefore be a suitable matrix to assess long-term exposure to these compounds and relationships with the tumorigenesis of these cancers. An LC-MS/MS assay for the determination of BPA and Clx-BPA in adipose tissue samples was developed and fully validated according to current bioanalytical validation guidelines. Ionization was achieved using an electrospray source operating in the negative mode and quantification of target analytes was obtained in the multiple reaction monitoring mode. Both standard and quality control (QC) samples were prepared in blank adipose tissue samples. Linearity was demonstrated over the ranges 0.125 to 8.000 and 0.0125-0.8000 ng/mL for BPA and Clx-BPA, respectively. Accuracy and precision were demonstrated over the whole concentration range: intra and inter-day bias values were in the 85-114% range and imprecision of the method did not exceed 14%. Lower limits of quantification were validated using QCs at 0.1250 and 0.0125 ng/mL for BPA and Clx-BPA, respectively. Internal standard-corrected matrix effects were comparable in breast and prostate adipose tissues, demonstrating that this method could be used to reliably assay BPA and Clx-BPA in both tissues. The method was sensitive enough to determine BPA and Clx-BPA in breast adipose tissue obtained from women undergoing breast surgery, enabling identification of different patterns of exposure to these ED chemicals. The method enables the reliable quantification of BPA and Clx-BPA in adipose tissue and could be used to assess long-term exposure to these compounds and potential associations with hormone-dependent cancers.

Chlorinated and brominated bisphenol A derivatives: Synthesis, characterization and determination in water samples.

Bisphenol A (BPA) has been used in the plastics industry for several decades. During the treatment of drinking water with chlorine reagent, the formation of chlorinated derivatives of BPA (ClxBPA) but also bromoBPA and bromochloroBPA is to be expected. Some of these compounds are considered to have an estrogenic effect and could induce major risks for human health by targeting different organs and systems in the body. In this paper, we describe the synthesis of chloro- and bromobisphenol A (ClxBPA, BrxBPA, BrxClxBPA)and their analytical characterization. These derivatives could be used as analytical standards in LC-MS/MS or evaluated in in vitro biological tests for their potential as endocrine disruptors. In this study, we evaluated the presence of BPA, ClxBPA in a pilot study from water samples. Range values found for BPA, ClxBPA were respectively 2.8-4169.3 ng/L and 0.8-11.3 ng/L.

Clinical practice guidelines from the French College of Gynecologists and Obstetricians (CNGOF): benign breast tumors - short text.

Screening with breast ultrasound in combination with mammography is needed to investigate a clinical breast mass (Grade B), colored single-pore breast nipple discharge (Grade C), or mastitis (Grade C). The BI-RADS system is recommended for describing and classifying abnormal breast imaging findings. For a breast abscess, a percutaneous biopsy is recommended in the case of a mass or persistent symptoms (Grade C). For mastalgia, when breast imaging is normal, no MRI or breast biopsy is recommended (Grade C). Percutaneous biopsy is recommended for a BI-RADS category 4-5 mass (Grade B). For persistent erythematous nipple or atypical eczema lesions, a nipple biopsy is recommended (Grade C). For distortion and asymmetry, a vacuum core-needle biopsy is recommended due to the risk of underestimation by simple core-needle biopsy (Grade C). For BI-RADS category 4-5 microcalcifications without any ultrasound signal, a minimum 11-G vacuum core-needle biopsy is recommended (Grade B). In the absence of microcalcifications on radiography cores additional samples are recommended (Grade B). For atypical ductal hyperplasia, atypical lobular hyperplasia, lobular carcinoma in situ, flat epithelial atypia, radial scar and mucocele with atypia, surgical excision is commonly recommended (Grade C). Expectant management is feasible after multidisciplinary consensus. For these lesions, when excision margins are not clear, no new excision is recommended except for LCIS characterized as pleomorphic or with necrosis (Grade C). For grade 1 phyllodes tumor, surgical resection with clear margins is recommended. For grade 2 phyllodes tumor, 10mm margins are recommended (Grade C). For papillary breast lesions without atypia, complete disappearance of the radiological signal is recommended (Grade C). For papillary breast lesions with atypia, complete surgical excision is recommended (Grade C).

[Can we enhance the one-day part in breast conservative surgery?]. / Est-il possible d'augmenter la part ambulatoire en chirurgie conservatrice du sein ?

INTRODUCTION: French national guidelines lead us to increase the part of one-day breast cancer conservative surgery. Our objective was to check if we can enhance our outpatient part and to identify solutions to improve our practices. METHODS: From 01/01/2013 to 31/12/2014, we conducted a monocentric and retrospective register about all cases of breast conservative surgery (infiltrating or in situ carcinoma, atypical hyperplasia). The collected data were: patients' sociodemographic characteristics, modality of hospitalization, surgical characteristics, preoperative exams organization, complications and reasons for an absence of surgery planned in one-day modality. We compared the two groups (one-day and standard hospitalization). RESULTS: We reported 324 surgeries of which 50.3% planned in one-day mode. The outpatient part increased from 39.8% in 2013 to 60.8% in 2014. There was no difference for postoperative complications between the two groups. We found a higher rate of outpatient for sentinel node axillary dissection in 2014 (65% versus 37% in 2013). We reported a rate of axillary dissection in one-day mode of 20%, of which 15% were drained. The proportion of patients unplanned in one-day mode without contraindications was reduced from 81% in 2013 to 57% for 2014. DISCUSSION: Increasing our outpatient part in breast conservative surgery was possible. There are still efforts to do to reach the national goals of one-day conservative breast cancer surgery, especially for the organizational aspects that remains the main obstruction. The implementation of pathways specifically for outpatient in and out of the hospital could be an interesting solution.

Improving perinatal Group B streptococcus screening with process indicators.

RATIONALE: Group B streptococcus (GBS) neonatal infection can be prevented by screening pregnant women for GBS colonization from the 34th to the 38th week of gestation, as has been recommended in France since 2001. We assessed guideline adherence among midwives and obstetricians. METHODS: From 2006 to 2008, new and mandatory GBS data were added to the obstetric database. We merged the latter with a bacteriological database and a paediatric database and defined process indicators for pregnant women who delivered from the 37th week of gestation in the hospital of Poitiers and for neonates hospitalized for a GBS infection from 2006 to 2008. RESULTS: We abstracted 5997 pregnant women (1942 in 2006, 1975 in 2007 and 2080 in 2008) and 84 neonates (17 in 2006, 32 in 2007 and 35 in 2008). GBS pregnancy colonization prevalence was 15%, 13% and 18% respectively. Availability of GBS screening status was stable (96%, P = 0.15). The rate of GBS screening during pregnancy increased significantly (86% to 90%, P = 0.002). Percentage of correct-term screening increased significantly (89% to 96%, P < 0.001). Percentage of women who received intra-partum antibiotic prophylaxis decreased significantly (84% to 70%, P = 0.001). Percentage of women who received correct intra-partum antibiotic prophylaxis was stable (75%, P = 0.65). Percentage of neonates whose mother had been correctly screened but negative was 77%, 67% and 68% respectively (P = 0.61). CONCLUSION: Our mandatory database entailed guideline adherence over a short lapse of time and resulted in a significant increase of the screening rate at the correct term. However, circumstances where neonates are infected still remain. Screening test performance needs to be re-evaluated.

Diagnosis and management of adult female stress urinary incontinence: guidelines for clinical practice from the French College of Gynaecologists and Obstetricians.

Urinary incontinence is a frequent affliction in women and may be disabling and costly {LE1}. When consulting for urinary incontinence, it is recommended that circumstances, frequency and severity of leaks be specified {Grade B}. The cough test is recommended prior to surgery {Grade C}. Urodynamic investigations are not needed before lower urinary tract rehabilitation {Grade B}. A complete urodynamic investigation is recommended prior to surgery for urinary incontinence {Grade C}. In cases of pure stress urinary incontinence, urodynamic investigations are not essential prior to surgery provided the clinical assessment is fully comprehensive (standardised questionnaire, cough test, bladder diary, post-void residual volume) with concordant results {PC}. It is recommended to start treatment for stress incontinence with pelvic floor muscle training {Grade C}. Bladder training is recommended at first intention in cases with overactive bladder syndrome {Grade C}. For overweight patients, loss of weight improves stress incontinence {LE1}. For surgery, sub-urethral tape (retropubic or transobturator route) is the first-line recommended technique {Grade B}. Sub-urethral tape surgery involves intraoperative risks, postoperative risks and a risk of failure which must be the subject of prior information {Grade A}. Elective caesarean section and systematic episiotomy are not recommended methods of prevention for urinary incontinence {Grade B}. Pelvic floor muscle training is the treatment of first intention for pre- and postnatal urinary incontinence {Grade A}. Prior to any treatment for an elderly woman, it is recommended to screen for urinary infection using a test strip, ask for a bladder diary and measure post-void residual volume {Grade C}. It is recommended to carry out a cough test and look for occult incontinence prior to surgery for pelvic organ prolapse {Grade C}. It is recommended to carry out urodynamic investigations prior to pelvic organ prolapse surgery when there are urinary symptoms or occult urinary incontinence {Grade C}.

Direct thrombin inhibitor prevents delayed graft function in a porcine model of renal transplantation.

BACKGROUND: Kidney transplantations from donors after cardiac arrest (DCA) are characterized by an increase in the occurrence of delayed graft function and primary nonfunction. In this study, Melagatran, a selective reversible direct thrombin inhibitor was used to limit renal injury in a DCA pig kidney transplantation model. METHODS: We used a porcine model of DCA to study the effects of treatment with Melagatran in the peri-conservation period. Thromboelastography was used to check Melagatran antithrombin effect on in vitro clot formation. Reverse-transcriptase polymerase chain reaction was used to analyze the peripheral immune cells activation status. Renal function and morphologic study were performed at days 1 and 7. Finally, we analyzed the mechanisms of Melagatran protection on kidney microvasculature primary endothelial cells. RESULTS: Prolongation of coagulation time (Ex-Tem) was observed 10 min after injection; however, Melagatran did not modulate increases of thrombin-antithrombin complexes following reperfusion. Melagatran significant treatment lowered the proinflammatory status of circulating immune cells. Animal's survival was increased in Melagatran-treated groups (9 of 10 in Melagatran groups vs. 4 of 10 in controls at day 7). Renal injury and inflammation were also significantly reduced in treated groups. We also demonstrated a direct protective effect of Melagatran against endothelial cell activation and inflammation in vitro. CONCLUSION: Direct thrombin inhibitor administration in the periconservation period improved graft outcome and reduced renal injury in a model of DCA.

Influence of warm ischemia time on peripheral-type benzodiazepine receptor: a new aspect of the role of mitochondria.

The peripheral benzodiazepine receptor (PBR) is located mainly in the outer mitochondrial membrane and many functions are associated directly or indirectly with the PBR. We have studied the influence of different durations of warm ischemia (WI) on renal function, tissue damage and PBR expression in a Large Whitepig model. After a midline incision, the renal pedicle was clamped for 10 (WI10), 30 (WI30), 45 (WI45), 60 (WI60) or 90 min (WI90), and blood and renal tissue samples were collected between 1 day and 2 weeks after reperfusion for assessment of renal function. Metabolite excretion associated with renal ischemia reperfusion injury such as trimethylamine-N-oxide (TMAO) was quantified in blood by magnetic resonance spectroscopy. PBR mRNA and protein expression were determined in renal tissue. TMAO levels rose progressively and significantly with increasing duration of WI. PBR mRNA expression was upregulated between 3 h and 1 day after reperfusion in WI30, WI45 and WI60. Its upregulation was noted 3 days after reperfusion in WI90. At day 14, PBR transcript expression was not different from basal level in any group. PBR protein followed the same pattern. These findings suggest a new role for PBR which could be a major target in the regeneration process during ischemia reperfusion.