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Introduction/Background* The management of ovarian cancer has rapidly become more complex in recent years due to surgical and medical advances. The aim of this study was to assess French current practice in management of patients with advanced epithelial ovarian cancer. Methodology An anonymous survey was sent to the SFOG, GINECO-ARCAGY and FRANCOGYN members. The survey consisted of 58 items divided in five sections dealing with diagnostic staging, pathological and genetic data, surgical practice patterns, adjuvant/neoadjuvant treatment, and follow-up strategies. Result(s)* Overall, 107 answers were available. Most of participants were obstetrician-gynecologists (37.4%), surgical oncologists (34.6%), and medical oncologists (17.8%). Most of participants came from University Hospitals (40.2%) and Comprehensive Cancer Center (37.4%). For 76.8% of respondents, less than 50% of patients are eligible for primary debulking surgery. In case of neoadjuvant chemotherapy, surgical resecability is assessed after 3 cycles for 92.7% of respondents. LION study’s criteria were always applied during primary surgery for 69,5% of respondents. Hyperthermic Intraperitoneal Chemotherapy (HIPEC) is used as a first-line treatment for 41.4% of respondents (26.8% within clinical trial and 14.6% outside) and during interval surgery for 37.8% of respondents. According to the completeness of cytoreduction surgery and the BRCA mutation status, association of Paclitaxel-Carboplatin (every 3 weeks) is the most used combination as adjuvant chemotherapy for 69.7 to 84.8% of respondents and bevacizumab 15mg/kg is used in case of no residual disease for 52.9 to 61.7 of respondents. In case of BRCA1-2 mutations, Olaparib is given by 75.8% to 84.8% of respondents. The delay to obtain BRCA germline mutation results is less than 1 month for 26.5% of respondents and less than 3 months for 76.5% of respondents. An Homologous Recombination Repair Deficiency is searched for 73.5% of respondents and mainly by Myriad test (91.3%). Conclusion* In our study, the rate of HIPEC was high because 2 clinical trials are currently ongoing in France on HIPEC as 1st line treatment. Our results provide an interesting picture of current management in France in relation to International Guidelines. They provide a basis for further research and raise the question of updating guidelines for ovarian cancer management.

Introduction/Background* The aim of this study was to investigate the current surgical and non-surgical therapeutic management of advanced epithelial ovarian cancer (AEOC) cases worldwide, using the data from an internationally launched survey. Methodology After the validation of a 58-item survey regarding diagnostic and pathological data, as well as surgical and chemotherapeutic strategies of AEOC in France, in the period between April and May 2021, the survey was launched among the members of the following gynecological cancer societies and study groups: IJGC Fellows, SENTICOL 3 study group, ARCAGY-GINECO, AGO, SFOG, SFOG Campus and FRANCOGYN. Result(s)* A total of 203 physicians completed the survey and majority of them, 171 (84.7%) were from Europe. Gynecological oncologists represented 49.2% of the respondents, surgical oncologists 25.1% and medical oncologists 13.7%. Most of the participants work in centers, managing more than 20 AEOC per year (91.5%). According to 66.7% of respondents, less than 50% of patients were eligible for primary debulking surgery (PDS). If neoadjuvant chemotherapy (NACT) was used, resectability was assessed after 3 cycles of NACT before interval debulking surgery (IDS) was performed. The most used peritoneal carcinomatosis index was Sugarbaker (69.8%), whereas Fagotti, modified Fagotti and Makar scores were used in 35.4%, 20.1% and 4.9%, respectively. After the initial staging, the decision between PDS and NADS-IDS was based on the number of the surgical procedures which had to be performed (82.9%), carcinosis index (61.6%), patient’s age (51.2%), global visual assessment (36.0%) and surgeon’s personal estimation (11.0%). During IDS, LION study’s criteria were always applied according to only 23.1% of the respondents. Hyperthermic intraperitoneal chemotherapy (HIPEC) was used as a first-line treatment from 16.0% of respondents within clinical trials and 14.1% out of clinical trials. Regardless of the surgical strategy (PDS or NACT-IDS) and the completeness of cytoreduction surgery, Olaparib was prescribed by 74.3% to 81.4% of the respondents and Niraparib by 8.6% to 12.9%. Bevacizumab was prescribed by 42.9% to 68.6% in case of no BRCA mutation. Conclusion* According to our study, the current management of ovarian cancer is in line with the ESGO guidelines. More participants are necessary for a more precise presentation.

In France, we are lacking an identified pathway for training in gynaecological cancer surgery. The four competent French learned societies, the SFOG, the CNGOF, the SFCO and the SCGP, supported by the CNU of ObstetricsGynaecology- and UNICANCER, agreed to materialize this course and attest it by a certification awarded by a national jury.The national committee of certification in gynaecological oncology made up of 10 members, representing the 6 concerned organizations, set itself 5 objectives: the definition of the eligibility criteria for training centres; the determination of a check-list to be filled by the candidate; the determination of a targeted curriculum for the training in gynecological oncological surgery; the determination of the assets necessary for the certification of a candidate already in practice; and the practical organization of the certification.Criteria for approval of centres for training included 150 gynaecological cancer cases per year, among which 100 excisional surgeries, including 20 advanced-stage ovarian cancers. For certification of candidate who followed the curriculum established by the committee or by validation of prior experience for an actual practitioner, a candidate must validate a logbook and fill out a checklist including 4 parts: theoretical and practical training; research and publications; teaching and subscription to a continuing education program. The accomplished elements of the logbook and the checklist will be evaluated by a score. The first certification session is planned for the end of 2021.The optimisation of the surgical management of patients treated for gynaecological cancer is achieved through the identification of a training course and the certification, by a national jury, of the skills of surgeons who have completed it.

BackgroundThe 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).MethodsAll 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.ResultsSome 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.ConclusionOverall and disease-free survival following treatment with CCRS and HIPEC is similar in patients with pseudomyxoma peritonei of appendicular or extra-appendicular origin.

Introduction/Background Surgery is the cornerstone of ovarian Granulosa Cell Tumor (GCT). Complete resection with adequate staging is the gold standard in 1st line setting. The aim of this study is to assess the impact of an appropriate surgery according to the guidelines. Methodology This is a nationwide five-year retrospective study, including 463 patients (of the 639 included patients) with a definitive diagnosis of GCT between 2011 and 2016. Medical and surgical practices were analyzed for conformity. Conformity to guidelines was defined by a conservative (unilateral salpingo-oophorectomy) or radical surgery (hysteretomy and bilateral salpingo-oophorectomy) including surgical staging (omentectomy, peritoneal biopsy and peritoneal cytology) according to the FIGO classification. Results Median age at diagnosis was 49 years old (range 10–89). The median size of tumor was 94 mm (range 5–400). Radical surgery was performed in 240 patients (51,8%), while a fertility-sparing surgery was performed in 98 cases (21,2%). A complete surgical staging was performed in only 76 cases (16,4%). 289 (62.4%) patients received an evaluation of the endometrium (hysterectomy or endometrial curettage). Surgery was fully compliant with the guidelines in 65 patients (14%), partially compliant in 213 patients (46%), non-compliant in 137 patients (29,6%) and not assessable in 48 cases (10,4%) respectively. A statistically significant improvement in the surgical management was observed among patients treated after 2012 compared to those treated before 2012. This Improvement included: endometrial evaluation (p=0,026), tumour rupture rate during surgery (p=0,010) and the global compliance of the surgery (p Conclusion Staging surgery provides a better assessment and an appropriate treatment of this rare tumors. According to this study, the implementation of a national network and guidelines dedicated to rare gynaecologic tumors seems to significantly improve the surgical management of the patients with GCT. Disclosure Nothing to disclose.

The French national rare gynecological tumor network has been established to improve the quality of care through offering expertise in double reading histological diagnosis, reviewing cases and guiding management of these tumors through specialized multidisciplinary tumor boards and online clinical guidelines (www.ovaire-rare.com). The aim of this study is to evaluate the impact of the development and implementation of this network by assessing the conformity of medical practice with the guidelines concerning the granulosa cell tumors (GCTs).This is a French nationwide study, including 463 patients (out of the 639 identified patients) with a definitive diagnosis of GCT between 2011 and 2016. Surgical practices were analyzed for conformity with the current guidelines (www.ovaire-rare.org). Medical records, surgical and pathological reports were systematically analyzed. Total conformity was defined by a conservative (unilateral salpingo-oophorectomy) or radical surgery (hysterectomy and bilateral salpingo-oophorectomy) including surgical staging (omentectomy, peritoneal biopsies and peritoneal cytology) according to the FIGO stage. Partial conformity referred to a conservative or radical surgery without surgical staging and non-conformity was defined as a non-optimal surgery as recommended by the guidelines.Median age at diagnosis was 49 years old (range 10-89). The median size of tumor was 94 mm (range 5-400). Radical surgery was performed in 240 patients (52%); while a fertility-sparing surgery was performed in 98 cases (21%). A surgical staging was performed in 76 cases (16%) and an evaluation of the endometrium in 289 cases (62%). Surgery was fully compliant with the guidelines in 65 patients (14%), partially compliant in 213 patients (46%), non-compliant in 137 patients (30%) and not assessable in 48 cases (10%). A statistically significant difference for compliance was observed in restaging surgery (p 0,001), radical surgery (p = 0,017) and the period (before or after) of the implementation of the network (p 0,001). Survival analyses did not allow us to demonstrate a significant difference in overall survival nor in PFS although there was a trend in favor of optimal surgery compared to incomplete/non optimal surgery.Surgical management's conformity to the guidelines increases over time from 2011 to 2016. According to this study, the implementation of a national network dedicated to rare gynecologic tumors seems to significantly improve the surgical management of the patients with ovarian granulosa cell tumors.

International audience; Adjuvant chemotherapy by carboplatin and paclitaxel is recommended for all high-grade ovarian and tubal cancers (FIGO stages I-IIA) (grade A). After primary surgery is complete, 6 cycles of intravenous chemotherapy (grade A) are recommended, or a discussion with the patient about intraperitoneal chemotherapy, according to her risk-benefit ratio. After complete interval surgery for FIGO stage III, hyperthermic intraperitoneal chemotherapy (HIPEC) can be proposed, in accordance with the modalities of the OV-HIPEC trial (grade B). In cases of postoperative tumor residue or in FIGO stage IV tumors, chemotherapy associated with bevacizumab is recommended (grade A).

International audience; An MRI is recommended for an ovarian mass that is indeterminate on ultrasound. The ROMA score (combining CA125 and HE4) can also be calculated (grade A). In presumed early-stage ovarian or tubal cancers, the following procedures should be performed an omentectomy (at a minimum, infracolic), an appendectomy, multiple peritoneal biopsies, peritoneal cytology (grade C), and pelvic and para-aortic lymphadenectomies (grade B) for all histologic types, except the expansile mucinous subtypes, for which lymphadenectomies can be omitted (grade C). Minimally invasive surgery is recommended for early-stage ovarian cancer, when there is no risk of tumor rupture (grade B). For FIGO stages III or IV ovarian, tubal, and primary peritoneal cancers, a contrast-enhanced computed tomography (CT) scan of the thorax/abdomen/pelvis is recommended (grade B), as well as laparoscopic exploration to take multiple biopsies (grade A) and a carcinomatosis score (Fagotti score at a minimum) (grade C) to assess the possibility of complete surgery (i.e., leaving no macroscopic tumor residue). Complete surgery by a midline laparotomy is recommended for advanced ovarian, tubal, or primary peritoneal cancer (grade B). For advanced cancers, para-aortic and pelvic lymphadenectomies are recommended when metastatic adenopathy is clinically or radiologically suspected (grade B). When adenopathy is not suspected and when complete peritoneal surgery is performed as the initial surgery for advanced cancer, the lymphadenectomies can be omitted because they do not modify either the medical treatment or overall survival (grade B). Primary surgery (before other treatment) is recommended whenever it appears possible to leave no tumor residue (grade B).

International audience; An MRI is recommended for an ovarian mass that is indeterminate on ultrasound. The ROMA score (combining CA125 and HE4) can also be calculated (Grade A). In presumed early-stage ovarian or tubal cancers, the following procedures should be performed an omentectomy (at a minimum, infracolic), an appendectomy, multiple peritoneal biopsies, peritoneal cytology (grade C), and pelvic and para-aortic lymphadenectomies (Grade B) for all histologic types, except the expansile mucinous subtypes, for which lymphadenectomies can be omitted (grade C). Minimally invasive surgery is recommended for early-stage ovarian cancer, when there is no risk of tumor rupture (grade B). Adjuvant chemotherapy by carboplatin and paclitaxel is recommended for all high-grade ovarian and tubal cancers (FIGO stages I-IIA) (grade A). For FIGO stage III or IV ovarian, tubal, and primary peritoneal cancers, a contrast-enhanced computed tomography (CT) scan of the thorax/abdomen/pelvis is recommended (Grade B), as well as laparoscopic exploration to take multiple biopsies (grade A) and a carcinomatosis score (Fagotti score at a minimum) (grade C) to assess the possibility of complete surgery (i.e., leaving no macroscopic tumor residue). Complete surgery by a midline laparotomy is recommended for advanced ovarian, tubal, or primary peritoneal cancers (grade B). For advanced cancers, para-aortic and pelvic lymphadenectomies are recommended when metastatic adenopathy is clinically or radiologically suspected (grade B). When adenopathy is not suspected and when complete peritoneal surgery is performed as the initial surgery for advanced cancer, the lymphadenectomies can be omitted because they do not modify either the medical treatment or overall survival (grade B). Primary surgery (before other treatment) is recommended whenever it appears possible to leave no tumor residue (grade B). After primary surgery is complete, 6 cycles of intravenous chemotherapy (grade A) are recommended, or a discussion with the patient about intraperitoneal chemotherapy, according to her risk-benefit ratio. After complete interval surgery for FIGO stage III disease, hyperthermic intraperitoneal chemotherapy (HIPEC) can be proposed, in accordance with the modalities of the OV-HIPEC trial (grade B). In cases of postoperative tumor residue or in FIGO stage IV tumors, chemotherapy associated with bevacizumab is recommended (grade A).

Faced to an undetermined ovarian mass on ultrasound, an MRI is recommended and the ROMA score (combining CA125 and HE4) can be proposed (grade A). In case of suspected early stage ovarian or fallopian tube cancer, omentectomy (at least infracolonic), appendectomy, multiple peritoneal biopsies, peritoneal cytology (grade C) and pelvic and para-aortic lymphadenectomy are recommended (grade B) for all histological types, except for the expansive mucinous subtype where lymphadenectomy may be omitted (grade C). Minimally invasive surgery is recommended for early stage ovarian cancer, if there is no risk of tumor rupture (grade B). Adjuvant chemotherapy with carboplatin and paclitaxel is recommended for all high-grade ovarian or Fallopian tube cancers, stage FIGO I-IIA (grade A). In case of ovarian, Fallopian tube or primitive peritoneal cancer of FIGO III-IV stages, thoraco-abdomino-pelvic CT scan with injection (grade B) is recommended. Laparoscopic exploration for multiple biopsies (grade A) and to evaluate carcinomatosis score (at least using the Fagotti score) (grade C) are recommended to estimate the possibility of a complete surgery (i.e. no macroscopic residue). Complete medial laparotomy surgery is recommended for advanced cancers (grade B). It is recommended in advanced cancers to perform para-aortic and pelvic lymphadenectomy in case of clinical or radiological suspicion of metastatic lymph node (grade B). In the absence of clinical or radiological lymphadenopathy and in case of complete peritoneal surgery during an initial surgery for advanced cancer, it is possible not to perform a lymphadenectomy because it does not modify the medical treatment and the overall survival (grade B). Primary surgery is recommended when no tumor residue is possible (grade B). After a complete first surgery, it is recommended to deliver 6 cycles of intravenous (grade A) or to propose intraperitoneal (grade B) chemotherapy, to be discussed with patient, according to the benefit/risk ratio. After a complete interval surgery for a FIGO III stage, the hyperthermic intra peritoneal chemotherapy (HIPEC) can be proposed in the same conditions of the OV-HIPEC trial (grade B). In case of tumor residue after surgery or FIGO stage IV, chemotherapy associated with bevacizumab is recommended (grade A).

National audience; Adjuvant chemotherapy with carboplatin and paclitaxel is recommended for all high-grade ovarian or Fallopian tube cancers, stage FIGO I-IIA (grade A). After a complete first surgery, it is recommended to deliver 6 cycles of intravenous (grade A) or to propose intraperitoneal (grade B) chemotherapy, to be discussed with patient, according to the benefit/risk ratio. After a complete interval surgery for a FIGO III stage, the hyperthermic intra peritoneal chemotherapy (HIPEC) can be proposed in the same conditions of the OV-HIPEC trial (grade B). In case of tumor residue after surgery or FIGO stage IV, chemotherapy associated with bevacizumab is recommended (grade A). For BRCA mutated patient, Olaparib is recommended (grade B).

National audience; Faced to an undetermined ovarian mass on ultrasound, an MRI is recommended and the ROMA score (combining CA125 and HE4) can be proposed (grade A). In case of suspected early stage ovarian or fallopian tube cancer, omentectomy (at least infracolonic), appendectomy, multiple peritoneal biopsies, peritoneal cytology (grade C) and pelvic and para-aortic lymphadenectomy are recommended (grade B) for all histological types, except for the expansive mucinous subtype where lymphadenectomy may be omitted (grade C). Minimally invasive surgery is recommended for early stage ovarian cancer, if there is no risk of tumor rupture (grade B). Laparoscopic exploration for multiple biopsies (grade A) and to evaluate carcinomatosis score (at least using the Fagotti score) (grade C) are recommended to estimate the possibility of a complete surgery (i.e. no macroscopic residue). Complete medial laparotomy surgery is recommended for advanced cancers (grade B). It is recommended in advanced cancers to perform para-aortic and pelvic lymphadenectomy in case of clinical or radiological suspicion of metastatic lymph node (grade B). In the absence of clinical or radiological lymphadenopathy and in case of complete peritoneal surgery during an initial surgery for advanced cancer, it is possible not to perform a lymphadenectomy because it does not modify the medical treatment and the overall survival (grade B). Primary surgery is recommended when no tumor residue is possible (grade B).

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 Z 42; ADJ: n Z 16; PO: n Z 16; NoC: n Z 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 Z 0.049). Major complications occurred for 41%, 45%, 35% and 41% of patients from NA, ADJ, PO and NoC groups, respectively (P Z 0.299). In multivariate analysis, NA was independently associated with worse OS (hazard ratio, 2.30; 95% confidence interval, 1.07e4.94; P Z 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.

Introduction et but de l’etude La sarcopenie, forme de denutrition initialement decrite chez les sujets âges, consiste en une demuscularisation chez des patients plus jeunes atteints de cancer. De plus en plus decrite, cette sarcopenie est a l’origine de complications graves en cours de chimiotherapie ou dans le peri-operatoire que ce soit en terme de complications post operatoires [1] ou de survie sans recidive [2] . De plus, la perte de masse musculaire semble evolutive en cours de chimiotherapie neoadjuvante [3] . Le but de cette etude retrospective, observationnelle sur une periode de 18 mois, est de rechercher la presence d’une eventuelle sarcopenie chez des patientes operees pour chirurgie de debulking pour carcinome ovarien apres chimiotherapie neoadjuvante. Materiel et methodes Vingt deux patientes ont ete incluses entre janvier 2015 et mars 2017. Criteres d’inclusion : patientes entre 18 et 85 ans, chimiotherapie neoadjuvante identique sur l’institut Bergonie, operees par le meme chirurgien pour une chirurgie notee comme optimale, classees GN2 a la consultation d’anesthesie c’est-a-dire non denutries dans les 3 semaines precedent l’acte operatoire. La recherche de la sarcopenie est realisee sur des coupes TDM en L3 de moins de 1 mois en pre chirurgical et analysee avec le logiciel slide o matic pour le calcul de la masse musculaire. L’albuminemie pre operatoire est recherchee systematiquement. Resultats et analyse statistique n = 22 % imc median albuminemie gr/l Âge median Sarcopenique 14 63,6 23,31 35,5 ± 4,7 70 Non sarcopenique 8 36,3 22,6 37,5 ± 7,6 64,5 Conclusion Si les patientes sarcopeniques sont plus âgees que les patientes non sarcopeniques, la frequence de cette forme de denutrition reste cependant tres elevee et surtout meconnue en preoperatoire. Les criteres classiques (perte de poids, albuminemie) utilises pour quantifier la denutrition en pre operatoire sont pris a defaut dans notre etude.

Adjuvant chemotherapy with carboplatin and paclitaxel is recommended for all high-grade ovarian or Fallopian tube cancers, stage FIGO I-IIA (grade A). After a complete first surgery, it is recommended to deliver 6 cycles of intravenous (grade A) or to propose intraperitoneal (grade B) chemotherapy, to be discussed with patient, according to the benefit/risk ratio. After a complete interval surgery for a FIGO III stage, the hyperthermic intra peritoneal chemotherapy (HIPEC) can be proposed in the same conditions of the OV-HIPEC trial (grade B). In case of tumor residue after surgery or FIGO stage IV, chemotherapy associated with bevacizumab is recommended (grade A). For BRCA mutated patient, Olaparib is recommended (grade B).

Faced to an undetermined ovarian mass on ultrasound, an MRI is recommended and the ROMA score (combining CA125 and HE4) can be proposed (grade A). In case of suspected early stage ovarian or fallopian tube cancer, omentectomy (at least infracolonic), appendectomy, multiple peritoneal biopsies, peritoneal cytology (grade C) and pelvic and para-aortic lymphadenectomy are recommended (grade B) for all histological types, except for the expansive mucinous subtype where lymphadenectomy may be omitted (grade C). Minimally invasive surgery is recommended for early stage ovarian cancer, if there is no risk of tumor rupture (grade B). Laparoscopic exploration for multiple biopsies (grade A) and to evaluate carcinomatosis score (at least using the Fagotti score) (grade C) are recommended to estimate the possibility of a complete surgery (i.e. no macroscopic residue). Complete medial laparotomy surgery is recommended for advanced cancers (grade B). It is recommended in advanced cancers to perform para-aortic and pelvic lymphadenectomy in case of clinical or radiological suspicion of metastatic lymph node (grade B). In the absence of clinical or radiological lymphadenopathy and in case of complete peritoneal surgery during an initial surgery for advanced cancer, it is possible not to perform a lymphadenectomy because it does not modify the medical treatment and the overall survival (grade B). Primary surgery is recommended when no tumor residue is possible (grade B).

Background Peritoneal metastasis from biliary carcinoma (PMC) is associated with poor prognosis when treated with chemotherapy. Objective To evaluate the impact on survival of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), and compare with conventional palliative chemotherapy for patients with PMC. Material and methods A prospective multicenter international database was retrospectively searched to identify all patients with PMC treated with a potentially curative CRS/HIPEC (CRS/HIPEC group). The overall survival (OS) was compared to patients with PMC treated with palliative chemotherapy (systemic chemotherapy group). Survival was analyzed using Kaplan-Meier method and compared with Log-Rank test. Results Between 1995 and 2015, 34 patients were included in the surgical group, and compared to 21 in the systemic chemotherapy group. In the surgical group, median peritoneal cancer index was 9 (range 3–26), macroscopically complete resection was obtained for 25 patients (73%). There was more gallbladder localization in the surgical group compared to the chemotherapy group (35% vs. 18%, p = 0.001). Median OS was 21.4 and 9.3 months for surgical and chemotherapy group, respectively (p=0.007). Three-year overall survival was 30% and 10% for surgical and chemotherapy group, respectively. Conclusion Treatment with CRS and HIPEC for biliary carcinoma with peritoneal metastasis is feasible and may provide survival benefit when compared to palliative chemotherapy.

Introduction Peritoneal metastasis (PM) of hepatocellular carcinoma (HCC) without distant spread are rare. The related prognosis is poor without standard treatment available. The role of cytoreduction surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is poorly documented. Methods An international multicentric cohort was constituted by retrospective analysis of 21 patients undergoing CRS/HIPEC for PM of HCC between 1992 and 2016 from 10 reference centers of PSOGI. Data on clinical features, treatment strategies, and survival outcomes were analyzed. Results The median time interval from the diagnosis of PM to the procedure was 4.5 months. The median peritoneal cancer index was 14. Sixteen patients had complete cytoreduction (CCR0-1). Ten patients had grades 3 to 4 complications. The median duration of follow-up was 52.2 months. The median OS was 46.7 months. The projected 3y-OS and 5y-OS were 88.9 and 49.4% respectively. The median OS for patients with CCR0-1 resection was not reached whereas it was 5.9 months for those with CCR2-3 resection after CRS (p = 0.0005). The median RFS was 26.3 months and projected RFS at 3 years of 36.5 months Three prognostic factors were associated with improved RFS in the univariate analysis: preoperative chemotherapy (p = 0.0156), PCI >15 (p = 0.009), Number of chemotherapy agents used for HIPEC (p = 0.005). Conclusion CRS/HIPEC is a safe and effective approach in selected patients with PM of HCC. CRS/HIPEC gives the patient a chance for a good relapse free and overall survival and should be considered as an option.

Une patiente de 66 ans, ayant pour principal antecedent une hysterectomie en 2010 (dans un contexte de dysplasie cervicale recidivante) est prise en charge chirurgicalement en 2014 pour un carcinome epidermoide du fond vaginal, suivie d’une curietherapie du fond vaginal realisee a haut debit de dose. Elle rechute en juillet 2015 au niveau ganglionnaire ainsi que localement au niveau du fond vaginal. Cette recidive hypermetabolique en TEP FDG est traitee en septembre 2015 par pelvectomie totale avec anastomose colorectale protegee et enterocystoplastie avec radiochimiotherapie concomitante. Dans les suites, elle presente une infection urinaire avec dilatation pyelo-calicielle, necessitant la mise en place d’une sonde double J par voie antegrade changee tous les 6 mois. Une augmentation du SCC en juillet 2018 (5 ng/mL pour une norme Conclusion La mise en evidence d’un hypermetabolisme ganglionnaire au TEP-FDG en contexte infectieux, d’autant plus s’il est associe a une reaction osteomedullaire diffuse, doit faire suspecter un processus inflammatoire. La connaissance de l’ensemble des donnees cliniques lors de l’exploration metabolique TEP est primordiale pour limiter les faux-positifs.

3,4-Diaminopyridine is used to treat some symptoms met in Lambert-Eaton myasthenia syndrome. It was shown efficient to reduce a form of variable muscle weakness and fatigability typical of the disease and correlated to a block of acetylcholine release. In France, 3,4-diaminopyridine is nowadays given to patients under capsules form and the status of hospital preparation. Whatever the diluant used in the formulation, the stability period could not exceed 12 months. Preliminary studies were made on a salt form in order to test the influence of various stress factors and determine if there is interaction between them. From this study, the most influent stress condition, presence of hydrogen peroxide, was selected and a comparative study was performed to compare the stability of molecular and salt species. Solutions of each species were exposed to 5 or 15% of hydrogen peroxide and analyzed at 8, 24, 72 and 216 h of degradation by HPLC-UV. Fractions of detected impurities were purified and collected by semi-preparative HPLC-UV and analyzed by HPLC-UV-ESI-MS and IR spectroscopy in order to determine their structure hypotheses. Theses experiments demonstrate that the salt species were more stable under oxidative stress condition than molecular species. The two main degradation products were collected and identified as 4-amino, 3-nitropyridine and 3,4-diaminopyridine-N-oxide when the molecular form was degraded whereas only 4-amino, 3-nitropyridine was found in less quantity in the salt solutions. Nitrogen pyridine and pyridine amine could not easily be oxidized by hydrogen peroxide in salt comparatively to molecular species due to the lone pair of electron engaged in a bound with hydrogen in the first case and by resonance change of the pyridine in the second case. This modification of structure promoted different pathways of degradation for the salt form which are more dependent of energy. Owing to the better stability of the salt species, a new pharmaceutical form containing it was developed to assess its stability under ICH standard conditions allowing an industrial manufacture of this drug.

A simple detection system with a high-performance liquid chromatography (HPLC) with positive ionisation-tandem mass spectrometry (ESI-MS/MS) for determining diphemanil methylsulphate (DMS) levels in human plasma using 4-diphemanylmethylene,1-methylpiperidine as an internal standard (I.S.), is proposed. The acquisition was performed with the multiple reactional monitoring (MRM) mode, by monitoring the transitions: m/z 278 > 262 for DMS and m/z 263 > 247 for the I.S. The method involved a simple single-step deproteinisation with acetonitrile. The analyte was chromatographed on a Zorbax® C18 reversed-phase chromatographic column by isocratic elution with 10−3 M ammonium acetate and 10−3 M hexafluorobutyric acid, adjusted to pH 7.0 with ammoniac/acetonitrile (40/60, v/v). The results were linear over the studied range (0.5–50.0 ng mL−1) and the total analysis time for each run was 10 min. The mean extraction apparent recoveries expressed at the 95% intervals of confidence were 94–104% for DMS and 92–106% for the I.S. The intra- and inter-assay precisions were 4.6–8.4% and 2.9–10.6%, respectively. The limit of quantification was 0.15 ng mL−1. The devised assay was successfully applied to the residual concentrations monitoring in infant.

Journal de Gynecologie Obstetrique et Biologie de la Reproduction - Vol. 35 - N° 7 - p. 711-719

In order to quantify a small amount of a drug, 3,4-diaminopyridine (3,4-DAP), in animal plasma samples, an analytical method was developed. It involved an extraction of 3,4-DAP and phenylephrine, used as internal standard (IS), from plasma with solid-phase extraction (SPE) on C18 cartridges. This analytical method is a hyphenated technique based on high-performance liquid chromatography with electrochemical detection (HPLC–EC) whose purpose is to obtain first a sensitive method and second a satisfying separation between 3,4-DAP and phenylephrine. The analytical method is accurate, specific, and linear between 10 and 500 μg of 3,4-DAP per litre. The recovery of 3,4-DAP is estimated at 70.8% with a 95% confidence interval of (66.0–75.6%). Intermediate precision was evaluated on three quality control samples; the intra-day precision was estimated at 13.5, 9.1, 7.8% and the inter-day precision at 17.9, 8.4, 9.3%. The limit of quantification of the method was evaluated at 10 μg l−1. First toxicokinetic parameters determined on dogs plasma samples after one 3,4-DAP oral administration of 1 mg kg−1 were: Cmax=395.7 μg l−1; Tmax=15 min; t1/2=113.6 min; Clearance/F=16.8 ml kg−1 min−1 and Vd/F=2.7 l kg−1.

NDP kinases are the non-specific enzymes which catalyse the synthesis of the NTPs through a transfer reaction using ATP as phosphoryl donor. In addition to their enzymatic activity, they display other not yet explained functions related to cell growth, differentiation and apoptosis, embryonic development, tumour progression and metastasis. In this study, the expression patterns of the three highly related NDP kinases A, B and C isoforms were investigated in the developing human trophoblast. Both NDP kinase A and B were found to be primarily present in the villous and extravillous cytotrophoblasts, while NDP kinase C was found almost exclusively in the syncytiotrophoblast layer. This suggests that NDP kinase A and B could be a marker for the mononuclear stage of differentiation of villous trophoblasts, while NDP kinase C could be a marker of the syncytiotrophoblast layer.

Cette étude tente d’évaluer les impacts des dragages réalisés dans le bassin de la Semois (Ardenne). Cette une étude interdisciplinaire se penche sur les aspects hydrauliques, environnementaux, géomorphologiques et sédimentologiques. L’étude géomorphologique et sédimentologique s’axe sur l’évolution de la dynamique fluviale via l’étude de carte et de photos anciennes. Une analyse du transport de la charge de fond de la rivière a aussi été menée afin de quantifier le taux de remblayage des différents dragages. L’aspect hydraulique se résume à l’application d’un modèle hydraulique (Bertrand, 1994) dans le but de cerner les effets des dragages sur le niveau d’eau. L’aspect environnemental consiste à évaluer les pertes d’habitabilité du fond du lit suite aux différents dragages grâce à l’usage du logiciel EVHA. Au final, les différents dragages ont eu peu d’effet en ce qui concerne la protection contre les inondations. Les temps de retour à la situation initiale ne dépassent pas 10 ans. Les pertes d’habitabilité pour la faune aquatique sont significativement importantes dans les sites dragués. This study aims to evaluate impacts of riverbed dredgings in the Semois catchment (Ardenne). This is an interdisciplinary study focused on the hydraulic, environmental, geomorphological and sedimentological aspects. The geomorphological and sedimentological study compare old maps and old photograph to highlight the general evolution of the river. Also, the bedload discharge has been calculated. A hydraulic model, (Bertrand, 1994) has been applied to evaluate the effect of dredging on the water level. The software EVHA has been used to evaluate the losses of fish’s habitat in the dredged sites. The dredging have low effect terms of flood protection and the time needed to recover the pre-works situation, and such works has reduced the environmental index in the dredged sites.

The triacylglycerol (TAG) composition study of cocoa butter (CB) and cocoa butter equivalents (CBEs) has been performed by gas chromatography (GC) and matrix-assisted laser desorption/ ionization time-of-flight mass spectrometry (MALDI-TOFMS). These two techniques provided comparable results. The advantage of the MALDI technique was the detection of each compound comprising the triacylglycerol classes (Cn). Moreover, comparison of the data obtained by these two techniques indicated that TAG relative percentages could be obtained quantitatively with the MALDI technique. These techniques have been applied for the composition determination of CB + CBE mixtures. Encouraging results showed that it is possible to quantify an admixture containing as little as 4% of CBE.

Diphemanil methylsulfate (DMS) is a synthetic antimuscarinic agent classically used in infants for vagal hypertonia-related symptoms. A normal-phase, isocratic liquid chromatographic method was developed for the quantitative determination of DMS in bulk drugs and in pharmaceutical forms. The method has been completely validated and robustness of this method has been studied. The limit of detection (LOD) for DMS impurities namely, impurity 1 and 2 were found to be 11 and 46 ng/ml. The limit of quantitation (LOQ) was found to be 49 and 139 ng/ml for impurity 1 and 2, respectively. The stability studies have been performed for 2 and 10 mg DMS tablets subjected at various temperatures: 25 degrees C (long term storage condition) and 40 degrees C (accelerated storage condition) for 18 and 6 months, respectively. At 25 degrees C, the samples were found to be stable for the study period. At 40 degrees C, 2 and 10 mg DMS tablets showed degradation up to 5 and 10% over a 6-month period.

Injectable solubilised arsenic trioxyde is tested as a new drug for acute promyelocytic leukaemia patients presenting a relapse after conventional chemotherapy. We used synchrotron radiation induced X-ray fluorescence spectroscopy to study this treatment and its elimination in hair. X-ray fluorescence spectra of hairs of patients having received the arsenic treatment have been recorded at coarse (5 mm steps) and fine (30 µm steps) resolution at the LURE (Orsay, France) and ESRF (Grenoble, France) synchrotron facilities, allowing us to follow the arsenic content in patient's hairs during and after therapy. Moreover, X-ray cartography of hairs cut in 30 µm slices (also recorded at the ESRF facility) provides the transversal distribution of As in hair.

Methacholine chloride is a powerful cholinergic bronchoconstrictor agent used during bronchial airway hyper-responsiveness diagnosis. Methacholine is susceptible to hydrolysis in aqueous solutions in acetic acid and beta-methylcholine. In the present work, kinetics of hydrolysis with different solvents (water and phosphate-buffered saline (PBS) pH 7.4) at different temperatures have been studied using a newly developed high-performance liquid chromatography. At 4 degrees C, kinetic determination of hydrolysis in methacholine chloride solutions (50 mg/ml) shows no hydrolysis in either aqueous or phosphate-buffered solutions over a 40-day period. At 30 degrees C, concentration of unbuffered methacholine chloride solutions remained unchanged, but buffered methacholine chloride solutions have degradation up to 5.5% over a 40-day period. At 40 degrees C, concentration of unbuffered methacholine chloride has degradation up to 5% and buffered methacholine chloride solutions have degradation up to 10% over a 40-day period. Methacholine chloride solutions are susceptibly to be used in hospital pharmacy at different concentrations. We have studied pH and osmolality for methacholine solutions prepared with different diluents potentially used in hospital pharmacies, i.e. deionized water, 0.9% NaCl and PBS pH 7.4. We have demonstrated that methacholine solutions prepared with deionized water at 50 mg/ml and diluted with PBS pH 7.4 from 5 to 40 mg/ml are isoosmotic and potentially available for inhalation tests to measure non-specific bronchial hyper-responsiveness.

An off-line system is proposed consisting of ion-pair reversed-phase liquid chromatography, collections of fractions at the outflow of the column and furnace atomic absorption spectrometry. The so-called system allowed determination of both arsenic and selenium species mainly found in the environment and in mammals (arsenite, arsenate, monomethylarsonate, dimethylarsinate, selenite, selenate, selenocystamine, selenocystine, selenomethionine and selenoethionine). In order to study the retention behaviour of these compounds and to estimate the optimal conditions for the chromatographic separation, central composite designs were used to evaluate the influence of the eluent parameters such as pH, tetrabutylammonium phosphate (TBA) concentration and sodium hydrogenphosphate amounts. The retention factors of each species and the selectivity were established as response criteria. Response surfaces and isoresponse curves were drawn from the mathematical models and enabled one to determine the optimal conditions and to visualise the method robustness. The predicted optimal zone was situated at pH 5.5-6.5, 4.0 mM Na2HPO4 and 3.0-4.0 mM TBA. Regression models suggested linearity for the studied compounds in the range 25-200 microg selenium and arsenic per litre investigated.

Central composite designs (CCDs) were used in the study of the ion-pair chromatographic separation of arsenic and selenium species in tap water: monomethylarsonate, dimethylarsinate, selenomethionine and selenite. The ternary eluent consisted of tetrabutylammonium phosphate (TBA), sodium hydrogenphosphate (Na2HPO4) and 1% acetonitrile. CCD allowed the investigation of the influence of the eluent parameters, which varied from 0.5 to 4.2 mmol l−1 Na2HPO4, 0.5 to 4.2 mmol l−1 TBA and pH 4.9 to 8.2, on the capacity factors (k′) of arsenic and selenium compounds. Furthermore, another mathematical model that permitted the variation of the chromatographic selectivity of species, computed from their retention data to be followed, was investigated. This showed the ability to locate the optimum conditions within the experimental design, so that arsenic and selenium species could be simultaneously quantified with good efficiency and resolution. A comparison between the predicted and the experimental response values was made in order to assess the prediction quality of the model. Response surfaces and isoresponse curves obtained from the mathematical models allowed the determination of the optimum chromatographic conditions and the robustness of the method. The predicted optimum zone allowing satisfactory determination of both arsenic and selenium compounds was pH 5.5–6.5, 2.5 mmol l−1 Na2HPO4 and 3.0–4.0 mmol l−1 TBA.

Diamagnetic niobium and tantalum complexes of general formula [M(η5-C5Me5)(dithiolene)2] have been prepared (M = Nb, dithiolene = dddt2– (5,6-dihydro-1,4dithiine-2,3-dithiolate) (1); M = Ta, dithiolene = dddt2– (2); M = Nb, dithiolene = dddt2– and dmit2– (1,3-dithiole-2-thione-4,5-dithiolate) (3)). All these complexes exhibit temperature-dependent 1H NMR spectra which result from a fluxional behavior of the dithiolene ligands. Their redox properties have been investigated by cyclic voltammetry and reversible oxidation processes involving the dithiolene ligands have been evidenced for the complexes 1 and 2.Key words: niobium, tantalum, dithiolene, voltammetry cyclic, variable-temperature 1H NMR.

Hydride generation inductively coupled plasma–atomic emission spectrometry (HG ICP–AES) was used as a continuous detection system for the determination of arsenic in the eluate from a high-performance liquid chromatographic (HPLC) system. Four arsenic species [arsenite As(III), arsenate As(V), monomethylarsonate (MMA), and dimethylarsinate (DMA)] present in the urine samples of patients treated intravenously with arsenite, were analyzed separately by HPLC–HG-ICP–AES using a non-polar C18 column. This analytical method allowed the sensitive determination of the arsenic species in the submicrogram per liter range. Urine samples collected on different days after arsenite administration were found to contain arsenite predominantly – monomethylarsonate and dimethylarsinate were also detected.

Immunoaffinity chromatography can be applied to the treatment of biological samples. It consists of the separation, extraction, or purification of a molecule (para nitro analine in this paper) from a mixture by a selective interaction with an antibody. The latter is produced by living organisms after their contact with an antigen (modified protein in this case). The production of specific antibodies highly depends on the purity of antigen. This paper describes and compares two methods of antigen purification: dialysis and gel permeation chromatography. This chromatographic method allows one to obtain a pure antigen faster than dialysis but with a slightly larger dilution of the samples. It is not a drawback for the procedure of the antibodies production.

An isocratic high-performance liquid-chromatographic (HPLC) procedure with diode-array detection has been developed for the determination of benzoylecgonine, cocaine, and cocaethylene in urine, serum, and saliva. After solid-phase extraction with mixed-mode extraction cartridges the three solutes are separated, in less than 20 min, by HPLC on a Supelcosil ABZ+column with 17∶83 (v/v) acetonitrile-0.04 M phosphate buffer, pH 2.3, as mobile phase. Unambiguous identification of the compounds was achieved by means of their retention times and UV spectra. Satisfactory resolution was obtained between interfering compounds, benzoylecgonine, cocaine, and cocaethylene. This analytical procedure proved suitable for the determination of cocaine and its metabolites in drug addicts' urine and saliva, and rabbit serum.

Through the psycho-anthropological approach study of the experiences of women affected by pelvic gynaecological cancer who undergo surgical treatment, this paper explores how these women perceive their bodily aesthetic and the impact this has on their sexuality and their relationship with their partner. Gynaecological cancers impact women in several ways, including having an effect on the way that they feel their femininity and appearance are perceived by others. Indeed, gynaecological cancer affects a part of the body intimately associated with representations of desirability that are linked to sexuality. Surgical procedures can cause scarring which can result in having a visible, physical impact on the patient, whilst also affecting their sense of body image and sexual identity. Healing treatments are too often associated with the visible, aesthetic appearance and the physicality of body, and neglect to treat questions of subjectivity. As such, women are compelled to feel like they have an integral body image, and that they are obliged to have a perfect body and need to be physically attractive to their partner.

The FEE cyclic hexapeptide (cFEE) is an investigational new drug added to the insemination medium in order to improve the in vitro fertilization rate. The pharmacological activity of small peptides is highly dependent on the conservation of the amino acid sequence and of the structural conformation of the active site. To enhance the scientific knowledge required for the clinical use of cFEE, a comprehensive determination of its chemical stability in solution was realized in accelerated conditions. Degradation products have been detected and identified by liquid chromatography/Qtrap ® mass spectrometry. The main degradation products highlighted during the product shelf life were produced by hydrolysis and only certain sites were involved. In most cases, the cyclic conformation was lost and regarding the major degradation pathway, the sequence representing the active site was affected.

Dietary fiber intake is associated with several beneficial effects on carbohydrate metabolism. Some authors have speculated that this improvement may be due to short-chain fatty acids (SCFA) produced by the colonic fermentation of dietary fibers. To test this hypothesis, six healthy men aged 26 +/- 2 (SE) yr with a body mass index of 20.9 +/- 0.7 received on three occasions an 18-h ileal perfusion infused at a flow rate of 3.3 ml/min, containing either 90 mmol/l of SCFA (60% acetate, 25% propionate, and 15% butyrate) (A), SCFA during the first 12 h and then a saline solution (A/S), or a saline solution (S). Basal hepatic glucose production (BHGP), insulin sensitivity (3-step euglycemic-hyperinsulinic clamp), and erythrocyte insulin binding (EIB) were studied 12 h after the beginning of the ileal perfusion. There was no change in BHGP or insulin sensitivity. However, maximal EIB was significantly different: 7.1 +/- 0.1 (A), 6.8 +/- 0.1 (A/S), vs. 6.5 +/- 0.1% (S) (P = 0.03). We conclude that acute administration of SCFA does not significantly alter glucose metabolism in healthy subjects.

Inclusion of anticoagulant drugs within the cavity of methyl-β-cyclodextrin in aqueous solution was studied by ultraviolet absorption, fluorimetry and reversed-phase liquid chromatography. Formation constants were obtained for complex formation of methyl-β-cyclodextrin with warfarin and 8-chlorowarfarin.

Modern methods described here, have for ultimate goal to check the main components of a wine label: geographical origin, real composition and vintage. Detecting counterfeiting, ensuring traceability, guaranteeing the authenticity of products and other investigations more in the judiciary domain have given us the opportunity to apply proven methodologies generally used in other areas (environment, geology, food-products in general).

Intraperitoneal (IP) insulin infusion with programmable implantable pumps is associated with a reduction in hypoglycaemic events when compared to intensive diabetes management with subcutaneous insulin in patients with Type 1 diabetes mellitus. The mechanism may involve more physiological insulin kinetics, lower peripheral insulin levels or a specific hepatic action of portal insulin on hypoglycaemic counter regulation. To investigate the latter two hypotheses, we performed two hypoglycaemic clamps (controlled blood glucose decrement to 2.2 mmol l-1) in random order in 12 Type 1 diabetic patients. Insulin was infused either IP or IV for 150 min, at rates chosen to generate similar peripheral insulin levels (1 mU/kg-1 min-1 IV or 2 mU/kg-1 min-1 IP, n = 6) to evaluate direct hepatic action, or at similar rates (1 mU/kg-1 min-1 IV and IP, n = 6) to evaluate IP indirect effects via lower peripheral insulinaemia. Hepatic glucose production and glucose utilization were measured by [6.6 2H] glucose dilution technique. Glucose production was lower (1.7 +/- 0.4 vs 0.5 +/- 0.4 mg kg-1 min-1, p < 0.05), and utilization was similar at the end of the matched-insulinaemia IV and IP clamps, respectively. By contrast, glucose production was higher (1.7 +/- 0.5 IV vs 2.7 +/- 0.3 IP mg kg-1 min-1, p < 0.01) and glucose utilization lower (4.4 +/- 1.0 IV vs 3.3 +/- 0.2 IP mg kg-1 min-1, p < 0.05) with IP delivery at the end of the matched-dose clamps. Counterregulatory hormones and hypoglycaemic symptoms increased similarly in all clamps. In summary, IP insulin, when compared to IV insulin at similar delivery rates, but not at similar insulinaemia, is associated with a less negative glucose balance (glucose production-glucose utilization) during hypoglycaemia. Such a mechanism may play a role in the reduced hypoglycaemic risk seen with IP implantable pumps.

The interaction of rutin and methyl-β-cyclodextrin in aqueous solution was studied by UV, fluorescence spectroscopy and reversed-phase liquid chromatography. Free solution capillary electrophoresis was also used as a new means of determination. Measurements from different methods yielded the formation constant for the 1:1 complex.

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