Obstetrical and neonatal complications in hereditary haemorrhagic telangiectasia: A retrospective study.

OBJECTIVE: To retrospectively describe a large series of pregnancies in women with hereditary haemorrhagic telangiectasia followed in our reference centre, plus neonatal outcomes, to better understand the risks of complications and to improve their prevention. DESIGN: A retrospective descriptive study conducted through a phone questionnaire. SETTING: Reference centre for hereditary haemorrhagic telangiectasia in Lyon, France. POPULATION: Women meeting the following criteria: (1) alive and aged ≥18 years; (2) with a definite clinical and/or genetic diagnosis of hereditary haemorrhagic telangiectasia; and (3) with at least one full-term pregnancy. MAIN OUTCOME MEASURES: Maternal and perinatal outcomes of pregnancies in women with hereditary haemorrhagic telangiectasia. RESULTS: Five hundred and sixty-two pregnancies were reported in 207 women with hereditary haemorrhagic telangiectasia. A total of 271 complications (48.2%) were registered. Of these, 149 (55%) non-specific complications, 110 (40.6%) non-severe specific complications and 12 (4.4%) severe specific complications were registered. There were four cases of haemoptysis and two cases of transient ischaemic attack related to pulmonary arteriovenous malformations. Four patients had severe decompensated dyspnoea, related to pulmonary arteriovenous malformations in three cases and to pulmonary arteriovenous malformations associated with severe hepatic arteriovenous malformations in one case. Hepatobiliary necrosis occurred in one case. Epidural or spinal anaesthesia was performed in 139 of 452 deliveries (31%), without complications. There were 12 reports of congenital anomalies in 461 live births (3%). CONCLUSIONS: Most pregnancies in hereditary haemorrhagic telangiectasia women are uneventful; complications are rare but can be severe. Women thus need to be educated about screening and possible pregnancy-related risks before becoming pregnant.

A New Option for Pain Prevention Using a Therapeutic Virtual Reality Solution for Bone Marrow Biopsy (REVEH Trial): Open-Label, Randomized, Multicenter, Phase 3 Study.

BACKGROUND: Evidence regarding the analgesic effect of distraction through immersion in virtual reality (VR) for care-induced pain has been documented in several phase 2 trials, but comparison with standard treatments in large, randomized studies is needed. OBJECTIVE: In this open-label, multicenter, randomized, phase 3 trial, we evaluated the safety and efficacy of a novel VR therapy solution for distraction in the context of bone marrow biopsy. METHODS: Bliss is a VR software with 4 imaginary interactive environments in 3 dimensions with binaural sound (head-mounted display). Efficacy regarding pain intensity was evaluated using a visual analog scale (VAS; score from 0 to 10) immediately after the biopsy. Secondary end points were anxiety and tolerance. Modified intention-to-treat analysis was performed. RESULTS: Overall, 126 patients with previously documented untreated or suspected malignant hemopathy between September 6, 2018, and May 18, 2020, were randomly assigned in a 1:1 ratio to receive pain prevention with a mixture of nitrous oxide/oxygen (MEOPA; n=63) or VR (n=63) before and during the bone marrow biopsy. We excluded 8 patients from the final analysis (3 in the MEOPA group and 5 in the VR group). All patients received local anesthesia (lidocaine) before biopsy. Follow-up was limited to 1 month after the biopsy. Participants' median age was 65.5 (range 18-87) years, and 54.2% (64/118) of patients were male. The average pain intensity was 3.5 (SD 2.6, 95% CI -1.6 to 8.6) for the MEOPA group and 3.0 (SD 2.4, 95% CI -1.7 to 7.7) for the VR group, without any significant differences in age, sex, center, and hemopathy (P=.26). Concerning anxiety, 67.5% (79/117; fear of pain questionnaire) of the patients were afraid before the biopsy, and anxiety scores were moderate to very high in 26.3% (30/114; revised Spielberger State-Trait Anxiety Inventory questionnaire) of the patients before the biopsy and 9.0% (10/114) after the biopsy for all patients, without a significant difference between the 2 groups (P=.83). Immersion in VR was well tolerated by the majority (54/57, 95%) of patients in the VR group. CONCLUSIONS: The intensity of pain did not significantly differ between both arms. VR was well tolerated, and the satisfaction of patients, nurses, and physicians was very high. VR could be an alternative treatment in case of contraindication or intolerance to MEOPA. TRIAL REGISTRATION: ClinicalTrials.gov NCT03483194; https://clinicaltrials.gov/ct2/show/NCT03483194.

Digestive toxicities after palliative three-dimensional conformal radiation therapy (3D-CRT) for cervico-thoracic spinal metastases.

OBJECTIVE: The palliative treatment for cervico-thoracic spinal metastases is based on a three-dimensional conformal radiation therapy (3D-CRT). Digestive toxicities are common and cause a clinical impact frequently underestimated in patients. We performed a retrospective study of digestive side effects occurring after palliative 3D-CRT for cervico-thoracic spinal metastases. PATIENTS AND METHODS: All patients receiving palliative 3D-CRT at Jean Bernard Center from January 2013 to December 2014 for spinal metastases between the 5th cervical vertebra (C5) and the 12th thoracic vertebra (T12) were eligible. Three-dimensional conformal RT was delivered by a linear accelerator (CLINAC, Varian). Premedication to prevent digestive toxicities was not used. Adverse events ("esophagitis" and "nausea and/or vomiting") were evaluated according to the NCI-CTCae (version 4). RESULTS: From January 2013 to December 2014, 128 patients met the study criteria. The median age was 68.6 years [31.8; 88.6]. Most patients (84.4%) received 30 Gy in 10 fractions. The median overall time of treatment was 13 days [3-33]. Forty patients (31.3%) suffered from grade ≥ 2 of "esophagitis" (35 grade 2 (27.4%) and 5 grade 3 (3.9%)). Eight patients (6.3%) suffered from grade ≥ 2 of "nausea and/or vomiting" (6 grade 2 (4.7%), 1 grade 3 (0.8%), and 1 grade 4 (0.8%)). CONCLUSION: The high incidence of moderate to severe digestive toxicities after palliative 3D-CRT for cervico-thoracic spinal metastases led to consider static or dynamic intensity-modulated radiation therapy (IMRT) to reduce the dose to organ at risk (the esophagus and stomach). Dosimetric studies and implementation in the clinic should be the next steps.

Totally implantable venous access ports: a prospective long-term study of early and late complications in adult patients with cancer.

PURPOSE: Totally implantable venous access ports (TIVAP) have been widely used for many years in the management of patients suffering from cancer. The implantation and long-term use of TIVAPs are associated with mechanical, thrombotic, and infectious complications. This is the first exhaustive prospective study of all complications occurring in a whole population on long-term follow-up and therefore allows an objective assessment to be made of the safety of TIVAPs. METHODS: We carried out a prospective single-center observational study. All adult patients with cancer who had a TIVAP implanted between January 1 and December 31, 2006 were registered. Early and late complications were recorded until the removal of the device, the patient's death, or until December 31, 2013. Exhaustive data concerning patients and TIVAP was recorded at time of implantation. RESULTS: Four hundred and ninety-three TIVAPs were implanted in 483 adult cancer patients and were followed during a period from 1 to 94 months (median = 18 months) representing a global quantity of 367,359 catheter-days. Eighty-seven complications were recorded (0.237/1000 catheter-days), including 37 infections (0.101/1000 catheter-days), 17 thrombotic events (0.046/1000 catheter-days), and 9 extravasations. Out of the 87 events, 62 (71.3%) occurred during the first year after implantation. Events were therefore extremely rare after 1 year. Thromboembolic and infectious complications were rare and no risk factors for these were found. CONCLUSIONS: This study demonstrates excellent tolerability, with only occasional complications. Most of these occurred during the year following implantation. A TIVAP may also be left in place for an extremely long time.

Bevacizumab with or without erlotinib as maintenance therapy in patients with metastatic colorectal cancer (GERCOR DREAM; OPTIMOX3): a randomised, open-label, phase 3 trial.

BACKGROUND: The combination of an anti-VEGF or an anti-EGFR-targeted monoclonal antibody with chemotherapy has shown clinical activity in patients with metastatic colorectal cancer. However, combining both anti-VEGF and anti-EGFR antibodies with chemotherapy in first-line treatment resulted in adverse outcomes. We assessed whether the combination of erlotinib, an EGFR tyrosine kinase inhibitor, with bevacizumab could increase the efficacy of maintenance therapy in patients with unresectable metastatic colorectal cancer. METHODS: This randomised, open-label, phase 3 study was undertaken in 49 centres in France, Austria, and Canada. Eligible patients were aged 18-80 years with histologically confirmed, unresectable metastatic colorectal cancer, WHO performance status 0-2, had received no previous therapy for metastatic disease, and had adequate organ function. Patients without disease progression after bevacizumab-based induction therapy were randomly assigned (1:1) by a minimisation technique to bevacizumab (7·5 mg/kg every 3 weeks) or bevacizumab plus erlotinib (150 mg once daily) as maintenance therapy until progression. All patients were stratified by centre, baseline performance status, age, and number of metastatic sites. The primary endpoint was progression-free survival on maintenance therapy analysed by intention to treat. We report the final analysis. This trial is registered with ClinicalTrials.gov, number NCT00265824. FINDINGS: Between Jan 1, 2007, and Oct 13, 2011, 700 eligible patients were enrolled; following induction treatment, patients without disease progression were randomly assigned to bevacizumab (n=228) or bevacizumab plus erlotinib (n=224). At the final analysis, median follow-up was 51·0 months (IQR 36·0-60·0) in the bevacizumab group and 48·3 months (31·5-61·0) in the bevacizumab plus erlotinib group. In the primary analysis (after 231 progression-free survival events), median progression-free survival from randomisation was 5·1 months (95% CI 4·1-5·9) in the bevacizumab plus erlotinib group compared with 6·0 months (4·6-7·9) in the bevacizumab group (stratified hazard ratio [HR] 0·79 [95% CI 0·60-1·06]; p=0·11; unstratified HR 0·76 [0·59-0·99]; p=0·043). In the final analysis, median progression-free survival from randomisation was 5·4 months (95% CI 4·3-6·2) in the bevacizumab plus erlotinib group compared with 4·9 months (4·1-5·7) in the bevacizumab group (stratified HR 0·81 [95% CI 0·66-1·01], p=0·059; unstratified HR 0·78 [0·68-0·96], p=0·019). At the final analysis, median overall survival from maintenance was 24·9 months (95% CI 21·4-28·9) in the bevacizumab plus erlotinib group and 22·1 months (19·6-26·7) in the bevacizumab group (stratified HR 0·79 [95% CI 0·63-0·99], p=0·036; unstratified HR 0·79 [0·64-0·98], p=0·035). The most frequent grade 3-4 adverse events were skin rash (47 [21%] of 220 patients in the bevacizumab plus erlotinib group vs none of 224 patients in the bevacizumab alone group), diarrhoea (21 [10%] vs two [<1%]), and asthenia (12 [5%] vs two [<1%]). INTERPRETATION: Maintenance bevacizumab plus erlotinib might be a new non-chemotherapy-based maintenance option for the first-line treatment of patients with unresectable metastatic colorectal cancer after bevacizumab-based induction therapy. FUNDING: GERCOR and F Hoffmann-La Roche.

Detection of lung cancer relapse using self-reported symptoms transmitted via an internet web-application: pilot study of the sentinel follow-up.

PURPOSE: We aimed to investigate whether patient self-evaluated symptoms transmitted via Internet can be used between planned visits to provide an early indication of disease relapse in lung cancer. METHODS: Between 2/2013 and 8/2013, 42 patients with lung cancer having access to Internet were prospectively recruited to weekly fill a form of 11 self-assessed symptoms called "sentinel follow-up". Data were sent to the oncologist in real-time between planned visits. An alert email was sent to oncologist when self-scored symptoms matched some predefined criteria. Follow-up visit and imaging were then organized after a phone call for confirming suspect symptoms. Weekly and monthly compliances, easiness with which patients used the web-application and the accuracy of the sentinel follow-up for relapse detection were assessed and compared to a routine visit and imaging follow-up. RESULTS: Median follow-up duration was 18 weeks (8-32). Weekly and monthly average compliances were 79 and 94 %, respectively. Sixty percents of patients declared to be less anxious during the few days before planned visit and imaging with the sentinel follow-up than without. Sensitivity, specificity, positive, and negative predictive values provided by the sentinel (planned imaging) follow-up were 100 %(84 %), 89 %(96 %), 81 %(91 %), and 100 %(93 %), respectively and well correlated with relapse (pχ (2) < 0.001). On average, relapses were detectable 5 weeks earlier with sentinel than planned visit. CONCLUSION: An individualized cancer follow-up that schedule visit and imaging according to the patient status based on weekly self-reported symptoms transmitted via Internet is feasible with high compliance. It may even provide earlier detection of lung cancer relapse and care.

Anaemia in Hospitalized Cancer Patients: A Retrospective Study of Two Cohorts before and after the Guideline Update.

INTRODUCTION: The incidence of anaemia and its consequences are often underestimated during cancer management. We propose to evaluate the situation before and after the recommendations were updated in order to assess their impact on the day-to-day practice. METHODS: In this single-centre retrospective study, eligible patients were treated for cancer and warranted overnight hospitalization over two periods (n = 206 in 2011, n = 143 in 2018). The diagnosis of anaemia was defined by a haemoglobin level below 12 and 13 g/dL for women and men, respectively. RESULTS: The prevalence of anaemia was 26% in 2011 and 16% in 2018 (p < 0.001). Biological assessment had changed between the two periods, with more tests of iron metabolism and measurements of inflammatory parameters. Patients hospitalized in 2018 had more advanced cancer and more severe anaemia (8.2 g/dL [±1.07] in 2011 vs. 7.9 g/dL [±1.18] in 2018). Rate of transfusion therapy did not change, but patients with mild and moderate anaemia were transfused less in 2018 (57% in 2011 vs. 44% in 2018). Intravenous iron and erythropoiesis-stimulating agent were used more frequently in 2018 (1 and 5 and 13 and 23% in 2011 and 2018, respectively), mainly for mild anaemia and life-threatening anaemia, respectively. Overall survival was poor in both cohorts at 24 months (15.4% in 2011 and 6.5% in 2018, p = 0.048). CONCLUSION: Practices have changed in the diagnosis of anaemia and prescriptions for erythropoiesis-stimulating agents and intravenous iron have increased. Efforts must continue to explore the causes of anaemia, optimize patients' quality of life, and reduce transfusions.

Concomitant chemoradiotherapy versus acceleration of radiotherapy with or without concomitant chemotherapy in locally advanced head and neck carcinoma (GORTEC 99-02): an open-label phase 3 randomised trial.

BACKGROUND: Concomitant chemoradiotherapy and accelerated radiotherapy independently improve outcomes for patients with locally advanced head and neck squamous-cell carcinoma (HNSCC). We aimed to assess the efficacy and safety of a combination of these approaches. METHODS: In our open-label phase 3 randomised trial, we enrolled patients with locally advanced, stage III and IV (non-metastatic) HNSCC and an Eastern Cooperative Oncology Group performance status of 0-2. We randomly allocated patients centrally with a computer program (with centre, T stage, N stage, and localisation as minimisation factors) in a 1:1:1 ratio to receive conventional chemoradiotherapy (70 Gy in 7 weeks plus three cycles of 4 days' concomitant carboplatin-fluorouracil), accelerated radiotherapy-chemotherapy (70 Gy in 6 weeks plus two cycles of 5 days' concomitant carboplatin-fluorouracil), or very accelerated radiotherapy alone (64·8 Gy [1·8 Gy twice daily] in 3·5 weeks). The primary endpoint, progression-free survival (PFS), was assessed in all enrolled patients. This trial is completed. The trial is registered with ClinicalTrials.gov, number NCT00828386. FINDINGS: Between Feb 29, 2000, and May 9, 2007, we randomly allocated 279 patients to receive conventional chemoradiotherapy, 280 to accelerated radiotherapy-chemotherapy, and 281 to very accelerated radiotherapy. Median follow-up was 5·2 years (IQR 4·9-6·2); rates of chemotherapy and radiotherapy compliance were good in all groups. Accelerated radiotherapy-chemotherapy offered no PFS benefit compared with conventional chemoradiotherapy (HR 1·02, 95% CI 0·84-1·23; p=0·88) or very accelerated radiotherapy (0·83, 0·69-1·01; p=0·060); conventional chemoradiotherapy improved PFS compared with very accelerated radiotherapy (0·82, 0·67-0·99; p=0·041). 3-year PFS was 37·6% (95% CI 32·1-43·4) after conventional chemoradiotherapy, 34·1% (28·7-39·8) after accelerated radiotherapy-chemotherapy, and 32·2% (27·0-37·9) after very accelerated radiotherapy. More patients in the very accelerated radiotherapy group had RTOG grade 3-4 acute mucosal toxicity (226 [84%] of 268 patients) compared with accelerated radiotherapy-chemotherapy (205 [76%] of 271 patients) or conventional chemoradiotherapy (180 [69%] of 262; p=0·0001). 158 (60%) of 265 patients in the conventional chemoradiotherapy group, 176 (64%) of 276 patients in the accelerated radiotherapy-chemotherapy group, and 190 (70%) of 272 patients in the very accelerated radiotherapy group were intubated with feeding tubes during treatment (p=0·045). INTERPRETATION: Chemotherapy has a substantial treatment effect given concomitantly with radiotherapy and acceleration of radiotherapy cannot compensate for the absence of chemotherapy. We noted the most favourable outcomes for conventional chemoradiotherapy, suggesting that acceleration of radiotherapy is probably not beneficial in concomitant chemoradiotherapy schedules. FUNDING: French Ministry of Health.

Hereditary haemorrhagic telangiectasia and pregnancy: a review of the literature.

BACKGROUND: Hereditary haemorrhagic telangiectasia (HHT) is a dominantly inherited genetic vascular disorder that has prevalence of 1:5000 to 1:8000, and which is characterised by recurrent epistaxis, cutaneous telangiectasia, and arteriovenous malformations (AVMs) that affect many organs including the lungs, gastrointestinal tract, liver, and central nervous system. The aim here was to carry out a review of the literature on HHT complications during pregnancy in order to guide management decisions. MAIN BODY: A literature review was carried out to analyse all publications on complications that occurred during pregnancy in women with HHT. The PubMed/Medline and Scopus databases were searched. The complications observed in HHT women during pregnancy were then described. The authors identified 5 case series and 31 case reports that describe the evolution of 1577 pregnancies in 630 women with HHT. The overall maternal death rate described in the case series was estimated at 1.0% of pregnancies in the case series and 2 maternal deaths occurred in 31 pregnancy case reports. Severe maternal complications occurred in 2.7 to 6.8% of pregnancies in the case series. Severe complications occurred mostly in the second and third trimester in non-diagnosed and non-screened HHT patients. Severe complications were related to visceral involvement. The most frequent complications were related to pulmonary arteriovenous malformations (PAVMs) (haemothorax (n = 10), haemoptysis (n = 4), and severe hypoxaemia (n = 3)). Neurological complications were related to PAVMs in one case (right to left shunt) and to cerebral arteriovenous malformations (CAVM) and intracranial haemorrhage in 2 cases. Complications were related to hepatic arteriovenous malformations (HAVMs) in 8 cases (acutely decompensated heart failure due to hepatic involvement (n = 1), dyspnoea related to heart failure (n = 5), and hepatobiliary necrosis (n = 2)). CONCLUSION: Based on the literature review, most pregnancies in HHT women occur normally. However, these pregnancies should be considered high-risk, given the potential life-threatening events related to AVM rupture. Furthermore, there is currently no international consensus regarding the medical follow-up of pregnancy in women with HHT and the aim here was to carry out a review of the literature in order to guide screening and management decisions for this rare disease.

Prognostic Value of Tumor Deposits for Disease-Free Survival in Patients With Stage III Colon Cancer: A Post Hoc Analysis of the IDEA France Phase III Trial (PRODIGE-GERCOR).

PATIENTS AND METHODS: A post hoc analysis of all pathologic reports from patients with stage III CC included in the IDEA France phase III study (ClinicalTrials.gov identifier: NCT00958737) investigating the duration of adjuvant fluorouracil, leucovorin, and oxaliplatin or capecitabine and oxaliplatin therapy (3 v 6 months) was performed. The primary objective was to determine the prognostic impact of TD on disease-free survival (DFS). The effect of the addition of TD to LNM count on pN restaging was also evaluated. A multivariable analysis was performed to establish the association between TD and DFS. RESULTS: Of 1,942 patients, 184 (9.5%) had TDs. The pN1a/b and pN1c populations showed similar DFS. TD-positive patients had worse prognosis compared with TD-negative patients, with 3-year DFS rates of 65.6% (95% CI, 58.0% to 72.1%) and 74.7% (95% CI, 72.6% to 76.7%; P = .0079), respectively. On multivariable analysis, TDs were associated with a higher risk of recurrence or death (hazard ratio [HR], 1.36; P = .0201). Other adverse factors included pT4 and/or pN2 disease (HR, 2.21; P < .001), the 3 months of adjuvant treatment (HR, 1.29; P = .0029), tumor obstruction (HR, 1.28; P = .0233), and male sex (HR, 1.24; P = .0151). Patients restaged as having pN2 disease (n = 35, 2.3%) had similar DFS as patients initially classified as pN2. CONCLUSION: The presence of TDs is an independent prognostic factor for DFS in patients with stage III CC. The addition of TD to LNM may help to better define the duration of adjuvant therapy.

Efficacy and safety of panitumumab in a cohort of patients with metastatic colorectal cancer in France: PANI OUEST, a post-EMA-approval descriptive study with a geriatric oncology focus.

BACKGROUND/AIMS: The Bretagne-Pays de la Loire cancer observatory, an oncology network created by the French Ministry of Health, is specifically dedicated to assess the use of new targeted anticancer therapies in routine practice. In line with the French National Cancer III program, our cancer network set up a real-life cohort, which is independent of the pharmaceutical industry, for patients with colorectal cancer to monitor patient safety and quality of care and promote pharmacovigilance. MATERIALS AND METHODS: Panitumumab monotherapy was assessed in 243 patients with wild-type Kirsten rat sarcoma who were treated for metastatic colorectal cancer (mCRC) between July 2008 and December 2010 after prior chemotherapy using oxaliplatine and irinotecan. This was a post-European medicine agency marketing (EMA-M) study Results: This study shed light on the best practices, strategic adaptations, clinical results (treatment objective responses, 13%; progression free survival, 2.99 months [2.73-3.15]; and overall survival, 6.8 months [5.49-8.38]) as well as expected or unexpected (grade 3 or 4: 11.5%) secondary effects in the phase IV panitumumab treatment of mCRC. CONCLUSION: Our results are similar to those by Amado whose phase III study led to obtaining EMA-M for panitumumab and tend to confirm the antitumor activity of this antiepidermal growth factor receptor antibody in the treatment of mCRC. In addition, our results opened avenues to further assessment of panitumumab use as monotherapy as well as its benefit-risk ratio while taking into account the patients' general and clinical characteristics. In 2012, the French National Authority for Health appended these data to the panitumumab transparency committee report.

European Reference Network for Rare Vascular Diseases (VASCERN) position statement on cerebral screening in adults and children with hereditary haemorrhagic telangiectasia (HHT).

Hereditary haemorrhagic telangiectasia (HHT) is a multisystemic vascular dysplasia inherited as an autosomal dominant trait. Approximately 10 % of patients have cerebral vascular malformations, a proportion being cerebral arteriovenous malformations (AVMs) and fistulae that may lead to potentially devastating consequences in case of rupture. On the other hand, detection and treatment related-risks are not negligible, and immediate. While successful treatment can be undertaken in individual cases, current data do not support the treatment of unruptured AVMs, which also present a low risk of bleeding in HHT patients. Screening for these AVMs is therefore controversial.Structured discussions, distinctions of different cerebrovascular abnormalities commonly grouped into an "AVM" bracket, and clear guidance by neurosurgical and neurointerventional radiology colleagues enabled the European Reference Network for Rare Vascular Disorders (VASCERN-HHT) to develop the following agreed Position Statement on cerebral screening:1) First, we emphasise that neurological symptoms suggestive of cerebral AVMs in HHT patients should be investigated as in general neurological and emergency care practice. Similarly, if an AVM is found accidentally, management approaches should rely on expert discussions on a case-by-case basis and individual risk-benefit evaluation of all therapeutic possibilities for a specific lesion.2) The current evidence base does not favour the treatment of unruptured cerebral AVMs, and therefore cannot be used to support widespread screening of asymptomatic HHT patients.3) Individual situations encompass a wide range of personal, cultural and clinical states. In order to enable informed patient choice, and avoid conflicting advice, particularly arising from non-neurovascular interpretations of the evidence base, we suggest that all HHT patients should have the opportunity to discuss knowingly brain screening issues with their healthcare provider.4) Any screening discussions in asymptomatic individuals should be preceded by informed pre-test review of the latest evidence regarding preventative and therapeutic efficacies of any interventions. The possibility of harm due to detection of, or intervention on, a vascular malformation that would not have necessarily caused any consequence in later life should be stated explicitly.We consider this nuanced Position Statement provides a helpful, evidence-based framework for informed discussions between healthcare providers and patients in an emotionally charged area.

Red, orange and green Caesarean sections: a new communication tool for on-call obstetricians.

OBJECTIVE: To evaluate the effect of a novel communication tool, related to the degree of urgency for Caesarean sections (CSs), on the decision-to-delivery interval for emergency CS. STUDY DESIGN: Red CS are very urgent cases corresponding to life-threatening maternal or foetal situations, orange CS are urgent cases and green CS are non-urgent intrapartum CS. We carried out this cohort study in a French maternity hospital. The study included all emergency Caesarean sections during two 6-month periods, before and after introduction of the code. We compared the decision-to-delivery interval of the two study periods. RESULTS: Our study included 174 emergency CS. The mean decision-to-delivery interval after introduction of the code was 31.7 min, significantly shorter (p=0.02) than the 39.6 min interval before introduction of the colour code. Except for the preparation time, each time interval decreased. This included transporting the patient into the operating theatre, and the incision-to-delivery time interval. CONCLUSION: This study suggests that the use of the three-colour code could significantly shorten the decision-to-delivery interval in emergency CS. Further prospective studies are needed to confirm this result.

Benefit of Risk Score-Guided Prophylaxis in Pregnant Women at Risk of Thrombotic Events: A Controlled Before-and-After Implementation Study.

BACKGROUND: Management of pregnant women at risk of venous thromboembolism (VTE) and placental vascular complications (PVCs) remains complex. Guidelines do not definitively specify optimal strategies. OBJECTIVE: Our objective was to evaluate the impact of employing risk score-driven prophylaxis strategies on VTE and PVC rates in at-risk pregnant women. MATERIALS AND METHODS: This study, conducted in 21 French maternity units, compared VTE and PVC rates before and after implementation of a risk scoring system to determine prophylactic strategies. RESULTS: A total of 2,085 pregnant women at risk of VTE or PVC were enrolled. Vascular events occurred in 190 (19.2%) patients before and 140 (13.0%) after implementation of risk score-driven prophylaxis (relative risk [RR] = 0.68 [0.55; 0.83]). The incidence of deep vein thrombosis during pregnancy was reduced (RR = 0.30 [0.14; 0.67]). PVC comprised mainly pre-eclampsia, occurring in 79 patients before and 42 patients after risk score implementation (RR = 0.52 [0.36; 0.75]). Post-partum haemorrhage occurred in 32 patients (3.2%) before and 48 patients (4.5%) after risk score implementation (RR = 1.38 [0.89; 2.13], p = 0.15). CONCLUSION: Use of a simple risk scoring system, developed by experts in VTE and PVC research to guide prophylaxis, reduced the risk of thrombotic events during pregnancy without any significant increase in bleeding risk.

Three Versus 6 Months of Oxaliplatin-Based Adjuvant Chemotherapy for Patients With Stage III Colon Cancer: Disease-Free Survival Results From a Randomized, Open-Label, International Duration Evaluation of Adjuvant (IDEA) France, Phase III Trial.

Purpose Reduction of adjuvant treatment duration may decrease toxicities without loss of efficacy in stage III colon cancer. This could offer clear advantages to patients and health care providers. Methods In International Duration Evaluation of Adjuvant Chemotherapy (IDEA) France, as part of the IDEA international collaboration, patient with colon cancer patients were randomly assigned to 3 and 6 months of modified FOLFOX6 (mFOLFOX6: infusional fluorouracil, leucovorin, and oxaliplatin) or capecitabine plus oxaliplatin (CAPOX) by physician choice. The primary end point was disease-free survival (DFS), and analyses were descriptive. Results A total of 2,010 eligible patients received either 3 or 6 months of chemotherapy (modified intention-to-treat population); 2,000 (99%) had stage III colon cancer (N1: 75%, N2: 25%); 1,809 (90%) received mFOLFOX6, and 201 (10%) received CAPOX. The median age was 64 years, and the median follow-up time was 4.3 years. Overall, 94% (3 months) and 78% (6 months) of patients completed treatment (fluoropyrimidines ± oxaliplatin). Maximal grade 2 and 3 neuropathy rates were 28% and 8% in the 3-month arm and 41% and 25% in the 6-month arm ( P < .001). Final rates of residual neuropathy greater than grade 1 were 3% in the 3-month arm and 7% in the 6-month arm ( P < .001). There were 578 DFS events: 314 and 264 in the 3- and 6-month arms, respectively. The 3-year DFS rates were 72% and 76% in the 3- and 6-month arms, respectively (hazard ratio [HR], 1.24; 95% CI, 1.05 to 1.46; P = .0112). In the 3 and 6-month arms, respectively, for patients who received mFOLFOX6, the 3-year DFS rates were 72% and 76% (HR, 1.27; 95% CI, 1.07 to 1.51); for the T4 and/or N2 population, they were 58% and 66% (HR, 1.44; 95% CI, 1.14 to 1.82); and for the T1-3N1 population, they were 81% and 83% (HR, 1.15; 95% CI, 0.89 to 1.49). Conclusion IDEA France, in which 90% of patients received mFOLFOX6, shows superiority of 6 months of adjuvant chemotherapy compared with 3 months, especially in the T4 and/or N2 subgroups. These results should be considered alongside the international IDEA collaboration data.

Preoperative treatment combining capecitabine with radiation therapy in rectal cancer: a GERCOR Phase II Study.

OBJECTIVE(S): To assess efficacy and tolerability of preoperative capecitabine chemoradiation in rectal cancer. METHODS: Patients received radiotherapy 45 Gy in 25 fractions over 5 weeks and capecitabine 825 mg/m(2) twice daily throughout radiotherapy. Surgery was performed 5-7 weeks after radiotherapy. The primary endpoint was pathological complete response, secondary endpoints were downstaging and tolerability. RESULTS: Fifty-one patients were enrolled in a phase II study, median age 62 years (range 35-78). Sixty-three percent of tumours involved the lower third of the rectum, 45% were fixed. The median delivered radiotherapy dose was 44.8 Gy (range 39.6-45.0 Gy) over 33-49 days. The treatment-related grade 3 adverse events were diarrhoea (12%), skin reactions (8%) and asthenia (8%), with no grade 4 toxicity. Fifty patients underwent surgery (29 conservative) and 1 patient refused. The pathological complete response rate was 20% and a further 10% of patients had minimal residual disease. Additional tumour downstaging was seen in 28% of patients and the sphincter preservation rate was 58%. CONCLUSIONS: Preoperative capecitabine chemoradiation is well tolerated and its efficacy supports further exploration, both as a single agent and as part of new therapeutic strategies.

Design of a new instrumented forceps: application to safe obstetrical forceps blade placement.

Today, medical simulators are increasingly gaining appeal in clinical settings. In obstetrics childbirth simulators provide a training and research tool for comparing various techniques that use obstetrical instruments or validating new methods. Especially in the case of difficult deliveries, the use of obstetrical instruments-such as forceps, spatulas, and vacuum extractors-has become essential. However, such instruments increase the risk of injury to both the mother and fetus. Only clinical experience acquired in the delivery room enables health professionals to reduce this risk. In this context, we have developed, in collaboration with researchers and physicians, a new type of instrumented forceps that offers new solutions for training obstetricians in the safe performance of forceps deliveries. This paper focuses on the design of this instrumented forceps, coupled with the BirthSIM simulator. This instrumented forceps allows to study its displacement inside the maternal pelvis. Methods for analyzing the operator repeatability and to compare forceps blade placements to a reference one are developed. The results highlight the need of teaching tools to adequately train novice obstetricians.

Characterization of hormonal profiles during the luteal phase in regularly menstruating women.

OBJECTIVE: To characterize the variability of hormonal profiles during the luteal phase in normal cycles. DESIGN: Observational study. SETTING: Not applicable. PATIENT(S): Ninety-nine women contributing 266 menstrual cycles. INTERVENTION(S): The women collected first morning urine samples that were analyzed for estrone-3-glucuronide, pregnanediol-3-alpha-glucuronide (PDG), FSH, and LH. The women had serum P tests (twice per cycle) and underwent ultrasonography to identify the day of ovulation. MAIN OUTCOME MEASURE(S): The luteal phase was divided into three parts: the early luteal phase with increasing PDG (luteinization), the midluteal phase with PDG ≥10 µg/mg Cr (progestation), and the late luteal phase (luteolysis) when PDG fell below 10 µg/mg Cr. RESULT(S): Long luteal phases begin with long luteinization processes. The early luteal phase is marked by low PDG and high LH levels. Long luteinization phases were correlated with low E1G and low PDG levels at day 3. The length of the early luteal phase is highly variable between cycles of the same woman. The duration and hormonal levels during the rest of the luteal phase were less correlated with other characteristics of the cycle. CONCLUSION(S): The study showed the presence of a prolonged pituitary activity during the luteinization process, which seems to be modulated by an interaction between P and LH. This supports a luteal phase model with three distinct processes: the first is a modulated luteinization process, whereas the second and the third are relatively less modulated processes of progestation and luteolysis.

Improving Survival in Patients Treated for a Lung Cancer Using Self-Evaluated Symptoms Reported Through a Web Application.

OBJECTIVES: We retrospectively compared survivals in patients with a lung cancer history and followed by the so-called sentinel Web-application that allows early detection of relapse and early palliative care initiation versus a conventional follow-up in our center. METHODS: The survival in 98 consecutive patients with lung cancer was assessed. The first part of them (the control arm) was retrospectively recruited between March 2011 and August 2012. The second half of them (the experimental arm) was prospectively recruited between August 2012 and December 2013 to weekly fill a form of 11 self-assessed symptoms, then processed by the "sentinel" Web-application. Data were sent to this sentinel application in real-time between planned visits. An email alert was sent to the oncologist when self-scored symptoms matched some predefined criteria. Follow-up visit and imaging were then organized after a phone call for confirming the suspect symptoms. In the control arm (49 patients), a common follow-up was applied (visit and imaging every 2 to 6 mo according to stage of tumor and kind of treatment). RESULTS: Median follow-up duration was 12.3 months in the experimental arm and 16.7 months in the control arm (P=0.27). Survival was significantly better in the sentinel arm than in the control arm (P=0.0014). Median survival was 16.7 months in the control arm and 22.4 months in the experimental arm. One-year survival was 86.6% in the experimental arm and 59.1% in the control arm. CONCLUSIONS: Survival may be improved by early detection of relapse and early palliative care initiation by using sentinel-like Web-application.

A new obstetric forceps for the training of junior doctors: a comparison of the spatial dispersion of forceps blade trajectories between junior and senior obstetricians.

OBJECTIVE: The purpose of this study was to create a new instrument for the training of doctors in the use of forceps and to compare the trajectories of forceps blades between junior and senior obstetricians. STUDY DESIGN: We equipped a simulator and forceps with spatial location sensors. The head of the fetus was in an occipitoanterior location, at a "+5" station. Forceps blade trajectories were analyzed subjectively with the 3-dimensional spatial graph and objectively based on 3 points of special interest. Each obstetrician performed 4 forceps blades placements. We compared the trajectories of junior and senior obstetricians. RESULTS: For senior operators, spatial dispersion was "excellent," "very good," or "good" in 92% of cases, whereas this was the case for only 38% of junior doctors (92% vs 38%; P < .001). CONCLUSION: A new instrument has been designed to demonstrate the trajectory of forceps blades during application in a simulator. The instrument captures the difference in experience between senior and junior clinicians.