Phenotypic characterisation of SMAD4 variant carriers.

BACKGROUND: Both hereditary haemorrhagic telangiectasia (HHT) and juvenile polyposis syndrome (JPS) are known to be caused by SMAD4 pathogenic variants, with overlapping symptoms for both disorders in some patients. Additional connective tissue disorders have also been reported. Here, we describe carriers of SMAD4 variants followed in an HHT reference centre to further delineate the phenotype. METHODS: Observational study based on data collected from the Clinical Investigation for the Rendu-Osler Cohort database. RESULTS: Thirty-three participants from 15 families, out of 1114 patients with HHT, had an SMAD4 variant (3%).Regarding HHT, 26 out of 33 participants (88%) had a definite clinical diagnosis based on Curaçao criteria. Complication frequencies were as follows: epistaxis (n=27/33, 82%), cutaneous telangiectases (n=19/33, 58%), pulmonary arteriovenous malformations (n=17/32, 53%), hepatic arteriovenous malformations (AVMs) (n=7/18, 39%), digestive angiodysplasia (n=13/22, 59%). No cerebral AVMs were diagnosed.Regarding juvenile polyposis, 25 out of 31 participants (81%) met the criteria defined by Jass et al for juvenile polyposis syndrome. Seven patients (21%) had a prophylactic gastrectomy due to an extensive gastric polyposis incompatible with endoscopic follow-up, and four patients (13%) developed a digestive cancer.Regarding connective tissue disorders, 20 (61%) had at least one symptom, and 4 (15%) participants who underwent echocardiography had an aortic dilation. CONCLUSION: We describe a large cohort of SMAD4 variant carriers in the context of HHT. Digestive complications are frequent, early and diffuse, justifying endoscopy every 2 years. The HHT phenotype, associating pulmonary and hepatic AVMs, warrants systematic screening. Connective tissue disorders broaden the phenotype associated with SMAD4 gene variants and justify systematic cardiac ultrasound and skeletal complications screening.

Ten (not so) simple rules for clinical trial data-sharing.

Clinical trial data-sharing is seen as an imperative for research integrity and is becoming increasingly encouraged or even required by funders, journals, and other stakeholders. However, early experiences with data-sharing have been disappointing because they are not always conducted properly. Health data is indeed sensitive and not always easy to share in a responsible way. We propose 10 rules for researchers wishing to share their data. These rules cover the majority of elements to be considered in order to start the commendable process of clinical trial data-sharing: Rule 1: Abide by local legal and regulatory data protection requirementsRule 2: Anticipate the possibility of clinical trial data-sharing before obtaining fundingRule 3: Declare your intent to share data in the registration stepRule 4: Involve research participantsRule 5: Determine the method of data accessRule 6: Remember there are several other elements to shareRule 7: Do not proceed aloneRule 8: Deploy optimal data management to ensure that the data shared is usefulRule 9: Minimize risksRule 10: Strive for excellence.

Efficacy and safety of intravenous bevacizumab on severe bleeding associated with hemorrhagic hereditary telangiectasia: A national, randomized multicenter trial.

BACKGROUND: Bevacizumab-a humanized monoclonal antibody-has been widely used to treat patients with hereditary hemorrhagic telangiectasia (HHT), but no randomized trial has yet been conducted. METHODS: This study is a double-blind multicenter randomized phase 2 trial with a 1:1 active-treatment-to-placebo ratio. We included patients over the age of 18 with a confirmed diagnosis and the need for at least four red blood cell (RBC) units transfused in the 3 months before study enrollment. Bevacizumab was administered at a dose of 5 mg/kg every 14 days with a total of six injections. The primary efficacy criterion was a decrease of at least 50% in the cumulative number of RBC units transfused in a 3-month period before and after treatment. RESULTS: A total of 24 patients (12 in each group) were included and randomized at 4 different centers. In intention-to-treat analysis, 63.6% of patients (7/11) in the bevacizumab group versus 33.3% of patients (4/12) in the placebo group decreased the number of blood transfusions by at least 50% (p = 0.22). Hemoglobin levels significantly improved at 6 months in the bevacizumab versus placebo group (p = 0.02). The pharmacokinetics study revealed that patients with high exposure to bevacizumab had a significant decrease in RBC transfusions (p = 0.03). Fifty-nine adverse events were observed, 34 in the placebo arm versus 25 in the bevacizumab arm. CONCLUSION: Though the present trial was underpowered, patients with HHT receiving bevacizumab required numerically fewer red blood cell transfusions than those receiving placebo, particularly those with high exposure.

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.

An International Registry of Peritoneal Carcinomatosis from Appendiceal Goblet Cell Carcinoma Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

PURPOSE: Peritoneal carcinomatosis from appendiceal goblet cell carcinoma (A-GCC) is a rare and aggressive form of appendiceal tumor. Cytoreductive surgery (CRS) and hyperthermic intra peritoneal chemotherapy (HIPEC) was reported as an interesting alternative regarding survival compared to surgery without HIPEC and/or systemic chemotherapy. Our aim was to evaluate the impact of CRS and HIPEC for patients presenting A-GCC through an international registry. METHODS: A prospective multicenter international database was retrospectively searched to identify all patients with A-GCC tumor and peritoneal metastases who underwent CRS and HIPEC through the Peritoneal Surface Oncology Group International (PSOGI). The post-operative complications, long-term results, and principal prognostic factors were analyzed. RESULTS: The analysis included 83 patients. After a median follow-up of 47 months, the median overall survival (OS) was 34.6 months. The 3- and 5-year OS was 48.5% and 35.7%, respectively. Patients who underwent complete macroscopic CRS had a significantly better survival than those treated with incomplete CRS. The 5-year OS was 44% and 0% for patients who underwent complete, and incomplete CRS, respectively (HR 9.65, p < 0.001). Lymph node involvement and preoperative chemotherapy were also predictive of a worse prognosis. There were 3 postoperative deaths, and 30% of the patients had major complications. CONCLUSION: CRS and HIPEC may increase long-term survival in selected patients with peritoneal metastases of A-GCC origin, especially when complete CRS is achieved. Ideally, randomized control trials or more retrospective data are needed to confirm CRS and HIPEC as the gold standard in this pathology.

EFFICACY AND SAFETY OF AFLIBERCEPT FOR THE TREATMENT OF IDIOPATHIC CHOROIDAL NEOVASCULARIZATION IN YOUNG PATIENTS: The INTUITION Study.

PURPOSE: To evaluate the mean change in visual acuity at 52 weeks in patients with idiopathic choroidal neovascularization treated with aflibercept. METHODS: We conducted a prospective noncomparative open-label Phase-II trial. The dosage regimen evaluated in this study was structured into two periods: (1) from inclusion to 20 weeks: a treat-and-extend period composed of three mandatory intravitreal injections, and complementary intravitreal injections performed if needed; (2) from 21 weeks to 52 weeks: a pro re nata period composed of intravitreal injections performed only if needed. RESULTS: A total of 19 patients were included, and 16 completed the 52-week study. At baseline, the mean best corrected visual acuity was 66.56 (±20.72) letters (≈20/50 Snellen equivalent), and the mean central retinal thickness was 376.74 µm (±93.77). At 52 weeks, the mean change in the best-corrected visual acuity was +19.50 (±19.36) letters [95% confidence interval = +9.18 to +29.82]. None of the patients included lost ≥15 letters at 24 weeks or 52 weeks. The mean change in central retinal thickness was -96.78 µm (±104.29) at 24 weeks and -86.22 µm (±112.27) at 52 weeks. The mean number of intravitreal injections was 5.4 (±3.0) at 52-weeks. No ocular serious adverse events related to the treatment were reported. CONCLUSION: The present analysis shows clinically significant functional and anatomical treatment effect of aflibercept in case of idiopathic choroidal neovascularization. The treat-and-extend regimen proposed after the first injection seems adequate to treat most neovessels.

Outcome of pretransplant melanoma after solid organ transplantation: an observational study.

The number of patients with a history of melanoma who are awaiting a solid organ transplantation (SOT) is increasing. Few recommendations exist on the timing to transplantation after melanoma diagnosis. The aim of this study was to assess the melanoma recurrence-free survival after pretransplant melanoma (PTM). We conducted a multicenter ambispective observational study. Organ transplant recipients (OTR) with a history of PTM and complete AJCC staging were included. Thirty-seven patients (predominantly men with a renal allograft) were included. Five melanomas were in situ, 21 stage IA, 4 stage IB, 5 stage II, and 2 stage IIIB. The median post-transplantation follow-up time was 4 years. Sixty-two percent of patients were followed up more than 2 years. Recurrence-free survival since melanoma reached 89.9%, but varied significantly according to AJCC staging (P = 0.0129). Three patients presented a recurrence. Despite the rather limited sample size and a wide range of follow-up, our findings concerning the recurrence-free survival appear reassuring for in situ and stage IA PTM; accordingly, we suggest that a waiting time to transplantation is not mandatory in patients with in situ or stage IA PTM, especially whenever SOT is urgently needed. Caution is, however, needed for patients with higher stage.

Safety and efficacy of a strategy of vitamin K antagonist reversal with prothrombin complex concentrates compared to vitamin K in patients with hip fracture.

Background: Increased preoperative delay in patients with hip fractures may be responsible for increased morbidity and mortality. We hypothesized that a strategy of reversal of vitamin K antagonist (VKA) by prothrombin complexes concentrates (PCCs), as compared to vitamin K, is safe and reduces preoperative delay and hospital length of stay (LOS). Methods: In this pilot study, we reviewed the records of patients admitted to a university-affiliated hospital for hip fracture between Jan. 1, 2012, and Dec. 31, 2016, who were taking VKA. Patients were stratified according to reversal strategy (vitamin K v. PCC). Adverse effects, time to surgery, LOS and mortality were collected from the electronic medical record and were compared between the 2 study groups and a control group not treated with VKA. Results: A total of 141 patients were included in the study: 65 in the vitamin K group, 26 in the PCC group and 50 in the control group. The median preoperative delay in the PCC group (20 h [interquartile range (IQR)] 13-25 h]) and the control group (20 h [IQR 15-33 h]) was lower than that in the vitamin K group (45 h [IQR 31-52 h]) (p < 0.001). Patients in the PCC group had a shorter median hospital LOS than those in the vitamin K group (6 d [IQR 4-9 d] v. 8 d [IQR 6-11 d], p < 0.05). No difference was observed in the proportion of patients who received a red blood cell transfusion, or had thrombotic or hemorrhagic complications. No difference in mortality at 12 months was observed between the groups. Conclusion: In patients with hip fracture, the use of PCCs as compared to vitamin K to reverse the effect of VKA significantly reduced preoperative delay and hospital LOS, and was not associated with an increase in the rates of thrombotic or hemorrhagic complications. Prospective studies involving a greater number of patients are required to confirm these promising results.

Contexte: L'allongement du délai préopératoire chez les patients atteints d'une fracture de la hanche pourrait expliquer l'augmentation de la morbidité et de la mortalité. Selon notre hypothèse, une stratégie d'inversion des antagonistes de la vitamine K (AVK) au moyen de concentrés de complexes prothrombiques (CCP), plutôt que de vitamine K, est sécuritaire et réduit le délai préopératoire et la durée du séjour hospitalier. Méthodes: Pendant cette étude pilote, nous avons passé en revue les dossiers de patients sous AVK admis dans un centre universitaire pour fracture de la hanche entre le 1er janvier 2012 et le 31 décembre 2016. Les patients ont été stratifiés selon la stratégie d'inversion choisie (vitamine K c. CCP). Les effets indésirables, le délai préopératoire, la durée du séjour hospitalier et la mortalité ont été recueillis à partir des dossiers médicaux électroniques et ont été comparés entre les 2 groupes de l'étude et un groupe témoin non sous AVK. Résultats: En tout, 141 patients ont été inclus dans l'étude, 65 dans le groupe sous vitamine K, 26 dans le groupe sous CCP et 50 dans le groupe témoin. Le délai préopératoire médian pour le groupe sous CCP (20 h [éventail interquartile (ÉIQ)] 13­25 h]) et le groupe témoin (20 h [ÉIQ 15­33 h]) a été plus bref que pour le groupe sous vitamine K (45 h [ÉIQ 31­52 h]) (p < 0,001). Les patients du groupe sous CCP ont eu un séjour hospitalier médian plus bref que les patients du groupe sous vitamine K (6 j [ÉIQ 4­9 j] c. 8 j [ÉIQ 6­11 j]) (p < 0,05). Aucune différence n'a été observée quant à la proportion de patients ayant reçu une transfusion de culot globulaire ou ayant manifesté des complications thrombotiques ou hémorragiques. Aucune différence quant à la mortalité à 12 mois n'a été observée entre les groupes. Conclusion: Chez les patients atteints d'une fracture de la hanche, l'utilisation des CCP plutôt que de la vitamine K pour inverser l'effet des AVK a significativement abrégé le délai préopératoire et la durée du séjour hospitalier, et n'a pas été associée à une augmentation des taux de complications thrombotiques ou hémorragiques. Des études prospectives sur un plus grand nombre de patients sont nécessaires pour confirmer ces résultats prometteurs.

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) might increase the risk of anastomotic leakage compared to HIPEC: an experimental study.

BACKGROUND: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) and hyperthermic intraperitoneal chemotherapy (HIPEC) are technics proposed to treat patients with peritoneal carcinomatosis, in different settings. There is some concern about an over-risk of anastomotic leakage (AL) with PIPAC jeopardizing a combination with cytoreductive surgery. This study used a healthy swine model to compare the postoperative AL rate between PIPAC and HIPEC with digestive resection and to analyze macrocirculation and microcirculation parameters. METHODS: Segmental colonic resection with a handsewn anastomosis was performed on 16 healthy pigs; 8 pigs had a PIPAC procedure with 7.5 mg/m2 cisplatin (PIPAC group), and 8 pigs had a closed HIPEC procedure with 70 mg/m2 cisplatin and 42 °C as the target intraperitoneal temperature (HIPEC group). Pigs were kept alive for 8 days, then sacrificed and autopsied to look for AL, which was defined as local abscess or digestive fluid leakage when pressure was applied to the anastomosis. Food intake, weight, and core temperature were monitored postoperatively. Macrocirculation (heart rate, systolic blood pressure) and microcirculation parameters (percentage of perfused vessels, perfused vessels density, DeBacker score) were evaluated intraoperatively at five timepoints. Results were compared between pigs with AL and those without. RESULTS: The HIPEC group had no AL, but 3 of 8 pigs (37.5%) had AL in the PIPAC group (p = 0.20). Heart rate and core temperature showed perioperative increases in the HIPEC group. Intraoperatively, heart rate was higher in the HIPEC group at the two last timepoints (123 vs. 93 bpm, p = 0.031, and 110 vs. 85 bpm, p = 0.010, at timepoints 3 and 4, respectively). Other macrocirculatory and microcirculatory parameters showed no significant differences. CONCLUSION: In this healthy swine model, PIPAC might have increased AL incidence compared to HIPEC. This potential over-risk did not seem to be related to changes in the microcirculation. PIPAC should probably not be used with digestive resection and should be avoided in cases of perioperative serosal injury.

PIPAC versus HIPEC: cisplatin spatial distribution and diffusion in a swine model.

Purpose: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel approach for delivering intraperitoneal chemotherapy and offers perspective in the treatment of peritoneal carcinomatosis. Concept is based on a 12 mmHg capnoperitoneum loaded with drug changed in microdoplets. It was postulated to guarantee a more homogeneous drug distribution and tissular uptake than hyperthermic intraperitoneal chemotherapy (HIPEC). The aim of this study was to compare cisplatin peritoneal distribution and pharmacokinetic between HIPEC and PIPAC procedures in a healthy swine model.Methods: Two groups of eight pigs underwent either HIPEC with cisplatin (70 mg/m2) at 43 °C for 60 min, or PIPAC with cisplatin (7.5 mg/m2) for 30 min. Postoperatively, peritoneal areas were biopsied allowing peritoneal cavity cartography. Tissular and plasmatic cisplatin concentrations were analyzed.Results: Cisplatin distribution was heterogeneous in both the groups with higher concentrations obtained closed to the delivery sites. Median total platinum peritoneal concentration by pig was higher in the HIPEC group than in the PIPAC group (18.0 µg/g versus 4.3 µg/g, p < .001) but the yield was 2.2 times better with PIPAC. Platinum concentrations were higher in the HIPEC group in all stations. At each time-point, cisplatin plasmatic concentrations were higher in the HIPEC group (p < .001) but beneath the toxicity threshold.Conclusions: With doses used in clinical practice, HIPEC guaranteed a higher cisplatin peritoneal uptake than PIPAC in this swine model. Spatial drug distribution was heterogeneous with both technics, with hotspots closed to the drug delivery sites. Nevertheless, considering the dose ratio, IP drug uptake yield was better with PIPAC.

Have ignorance and abuse of authorship criteria decreased over the past 15 years?

OBJECTIVE: A high prevalence of authorship problems can have a severe impact on the integrity of the research process. We evaluated the authorship practices of clinicians from the same university hospital in 2019 to compare them with our 2003 data and to find out if the practices had changed. METHODS: Practitioners were randomly selected from the hospital database (Hospices Civils de Lyon, France). The telephone interviews were conducted by a single researcher (HM) using a simplified interview guide compared with the one used in 2003. The doctors were informed that their answers would be aggregated without the possibility of identifying the respondents. During the interviews, the researcher ticked the boxes with the answers on a paper file. RESULTS: We interviewed 26 clinicians (mean age 49±8 years) from various medical specialties. They were unfamiliar with the ICMJE (International Committee of Medical Journal Editors) criteria for writing medical articles and felt that these criteria were not well met in general. With regard to ways of reducing the practice of honorary authors, the participants clearly felt that asking for a signature was hypocritical and of little use. The ghost authors were well known; this practice was considered as rather rare. The 'publish or perish' has always been cited as being responsible for bad practices (26/26: 100%). We compared these results with those observed in 2003 and no improvement has been observed in the past 15 years. CONCLUSION: For the second time in France, within a 15-year interval, we have shown that the ICMJE criteria were ignored and that honorary authorship was frequent.

Flow Diverters for Intracranial Aneurysms: The DIVERSION National Prospective Cohort Study.

Background and Purpose- Flow diverters are used for endovascular therapy of intracranial aneurysms. We did a nationwide prospective study to investigate the safety and effectiveness of flow diversion at 12 months. Methods- DIVERSION was a national prospective cohort study including all flow diverters placement between October 2012 and February 2014 in France. The primary end point was the event-free survival rate at 12 months, defined as the occurrence of morbidity (intracranial hemorrhage, ischemic stroke, noncerebral hemorrhage, or neurological deficit due to mass effect), retreatment, or death within 12 months post-treatment. A quality control was carried out on 100% of the collected data and of at least 10% of the included patients in each center, chosen at random. All reported serious events were adjudicated by an independent Data Safety and Monitoring Board. Satisfactory occlusion was defined as 3 or 4 on Kamran scale by an independent imaging core laboratory at 12 months. Results- We enrolled 398 patients harboring 477 intracranial aneurysms. At least 1 morbidity-mortality event was noted in 95 of 408 interventions representing an event-free survival rate of 75.7% (95% CI, 71.1-79.7). The rate of permanent-related serious events and mortality was 5.9% and 1.2% at 12 months, respectively. Multivariate analysis showed that high baseline blood pressure (hazard ratio, 2.54; 95% CI, 1.35-4.79; P=0.039), diabetes mellitus (hazard ratio, 3.70; 95% CI, 1.60-8.6; P=0.0022), and larger aneurysms (hazard ratio, 1.07; 95% CI, 1.04-1.11; P<0.0001) were associated with the occurrence of a neurological deficit. The satisfactory occlusion rate at 12 months was 79.9%, and the absence of high baseline blood pressure (odds ratio, 2.01; 95% CI, 1.12-3.71; P=0.0193) and postprocedural satisfactory occlusion (odds ratio, 2.75; 95% CI, 1.49-5.09; P=0.0012) were associated with a 12-month satisfactory occlusion. Conclusions- A satisfactory occlusion was achieved in almost 80% of cases after flow diverter treatment with a permanent-related serious event and mortality rates of 5.9% and 1.2% at 12 months, respectively.

Assessment of Dural Ectasia Using Computed Tomodensitometry as a Criterion in Marfan Syndrome.

OBJECTIVE: The aim of this study was to reevaluate dural ectasia criteria in Marfan syndrome patients fulfilling the revised Ghent criteria. METHODS: Lumbar computed tomography scans of 19 Marfan patients and 30 matched control subjects were retrospectively assessed. Dural sac ratio (DSR), nerve root sleeve diameter, pedicle width, and a scalloping or meningocele presence were each assessed by 2 readers blinded from the diagnosis. Mann-Whitney-Wilcoxon tests compared the patient and control groups. Receiver operating characteristic curve analysis and multivariate models determined the optimal cutoff value. RESULTS: A DSR value greater than 0.69 at L5 (DSR-L5) such as L4 scalloping of more than 2.65 mm (scall-L4) and 6 or more vertebrae showing a scalloping of more than 3 mm (6-scall) were found very specific but with limited sensitivity. Multivariate model combining DSR-L5 + scall-L4 showed good positive predictive value, whereas model combining DSR-L5 + 6-scall showed good negative predictive value. CONCLUSIONS: Assessment of DSR and vertebral scalloping allows valuable depiction of dural ectasia in Marfan syndrome patients.

Pregnancy Outcomes in French Hemodialysis Patients.

BACKGROUND: Pregnancy in hemodialysis (HD) women is a rare event and often associated with maternal and fetal complications. Scarcity of available data from large cohorts impedes fair medical counseling. METHODS: This is a descriptive, retrospective, multi-centric study. Pregnant women on HD during the period from 1985 to 2015 in France were included. The primary outcome was a living infant discharged from hospital, while secondary outcomes included gestational age and birth weight. RESULTS: We identified 100 pregnancies in 84 women on HD, from 41 centers. Chronic HD was initiated during pregnancy for 17.7% (14/79) of patients explaining a 19.8% prevalence of catheter (19/96) and a preserved residual diuresis for 50% of pregnancy (43/86). Seventy-six (89.4%) women performed daily dialysis during the third trimester (6 times per week). Our primary outcome was met for 78% of newborns with a mean gestational age of 33.2 ± 3.9 weeks and a mean birth weight of 1,719 ± 730 g. CONCLUSIONS: Our study is one of the largest series of -pregnancies in HD patients. Despite recent progresses, these pregnancies remain at high risk, reinforcing the need for an early nephrologist-obstetrician skilled team co-management.

Pulmonary arteriovenous malformations in hereditary haemorrhagic telangiectasia: Correlations between computed tomography findings and cerebral complications.

OBJECTIVES: Computed tomography (CT) is the modality of choice to characterise pulmonary arteriovenous malformations (PAVMs) in patients with hereditary haemorrhagic telangiectasia (HHT). Our objective was to determine if CT findings were associated with frequency of brain abscess and ischaemic stroke. METHODS: This retrospective study included patients with HHT-related PAVMs. CT results, i.e. PAVM presentation (unique, multiple, disseminated or diffuse), the number of PAVMs and the largest feeding artery size, were correlated to prevalence of ischaemic stroke and brain abscess. All CTs were reviewed in consensus by two radiologists. RESULTS: Of 170 patients, 73 patients had unique (42.9 %), 49 multiple (28.8 %), 36 disseminated (21.2 %) and 12 diffuse (7.1 %) PAVMs. Fifteen patients presented with brain abscess; 26 patients presented with ischaemic stroke. The number of PAVMs was significantly correlated with brain abscess (11.5 vs. 6.2, respectively; p=0.025). The mean diameter of the largest feeding artery was significantly correlated with ischaemic stroke frequency (4.9 vs. 3.2 mm, respectively; p=0.0098). CONCLUSIONS: The number of PAVMs correlated significantly with risk of brain abscess, and a larger feeding artery significantly with more ischaemic strokes. These findings can lead to a better recognition and management of the PAVMs at risk of cerebral complications. KEY POINTS: • Chest CT helps clinicians to facilitate appropriate PAVM management strategies. • Pulmonary arteriovenous malformation CT findings are correlated with risk of cerebral complications. • Risk of brain abscess is significantly correlated with number of PAVMs. • Risk of ischaemic stroke is significantly correlated with large feeding artery PAVMs. • Prevalence of observed of brain abscess and ischaemic stroke is 26 %.

Subsequent nonmelanoma skin cancers and impact of immunosuppression in liver transplant recipients.

BACKGROUND: Nonmelanoma skin cancers (NMSCs) are the most frequent cancers in solid organ transplant recipients, with a high rate of subsequent tumors. OBJECTIVES: To describe subsequent NMSCs in a large cohort of liver transplant recipients (LTRs) with long follow-up and analyze the factors influencing it, including immunosuppressive regimen. METHODS: A total of 96 LTRs (76 male) with a personal post-transplant history of squamous cell carcinoma, basal cell carcinoma or Bowen's disease were included, with a median follow-up of 12.4 years (range, 1.5-27.8) after liver transplantation. RESULTS: The median follow-up after first NMSC was 6.4 years (range, 0.17-22.1). In all, 52 patients (53.1%) developed 141 subsequent NMSCs with a basal cell carcinoma-to-squamous cell carcinoma ratio of 1.8:1. The actuarial risk for development of a second NMSC was 13.7% at 1 year, 28.4% at 2 years, 49.4% at 5 years, 65.7% at 10 years, and 88.4% at 15 years. Multivariate analysis found that skin phototype I or II (vs III or IV) was a significant risk factor for development of a second NMSC (hazard ratio, 2.556; 95% confidence interval, 1.45-4.48; P = .001), whereas withdrawal of calcineurin inhibitors was significantly protective (hazard ratio, 0.358; 95% confidence interval, 0.142-0.902; P = .029). LIMITATIONS: Retrospective analysis. CONCLUSIONS: Subsequent NMSCs are very frequent in LTRs, and conversion from a calcineurin inhibitor-based immunosuppressive regimen to a mammalian target of rapamycin inhibitor/antimetabolite-based immunosuppressive regimen can reduce subsequent NMSCs.

Long-term survival in patients with epithelial ovarian cancer following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC).

OBJECTIVE: Despite a high response rate to first-line therapy, prognosis of epithelial ovarian carcinoma (EOC) remains poor. The objective of the present study was to evaluate the frequency of long-term survivors and to identify the prognostic factors associated with long-term survival in a French cohort of 566 patients. METHODS: Patients treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for EOC in 13 French centers between 1991 and 2010 were included. Long-term survivors were defined as patients who survived more than 5 years after HIPEC and CRS, irrespective of relapse. RESULTS: Seventy-eight long-term survivors were analyzed. The median follow-up was 74 months. Median age at the time of first HIPEC was 55.4 years (range [22.6-77.6]. Seven patients had advanced EOC and 71 patients had recurrent EOC (37 patients had platinum-resistant EOC and 32 had platinum-sensitive disease). More than half of the long-term survivors had high-grade serous ovarian cancer (HGSOC). In univariate analysis, age ≥50 years (p = .004), peritoneal cancer index (PCI) ≤ 8 (p = .049) and CA-125 < 100 (p = .02) were associated with long-term survival. There was a trend towards an association between higher CC-score and long-term survival (p = .057). CONCLUSION: Age ≥50 years, PCI ≤8 and CA125 < 100 were associated with long-term survival in univariate analysis. There was a trend towards the significance of CC-score. Platinum-status was not associated with long-term survival.

PREDICTORS OF ONE-YEAR VISUAL OUTCOMES AFTER ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR TREATMENT FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To determine predictors of best-corrected visual acuity (BCVA) outcomes 1 year after ranibizumab or bevacizumab treatment for neovascular age-related macular degeneration, within the French Study Group Avastin versus Lucentis for neovascular age-related macular degeneration (GEFAL). METHODS: Patients aged ≥50 years presenting subfoveal neovascular age-related macular degeneration were randomized to receive ranibizumab or bevacizumab (3 monthly intravitreal injections followed by an as-needed regimen). The main outcome measures were BCVA and its change from baseline at 1 year. Variables with a P value <0.20 in the univariate model and/or which were clinically relevant were included in the multivariate analysis. RESULTS: The following baseline factors were associated with a lower BCVA score at 1 year and with less improvement in BCVA (multivariate analysis): intraretinal fluid, thickness of central subfield macular ≤277 µm, predominantly classic choroidal neovascularization, and total area of choroidal neovascularization (all P ≤ 0.01). Pigment epithelium detachment and high baseline BCVA were associated with less improvement in BCVA (P = 0.03, P = 0.05, respectively). Patients who met retreatment criteria but did not receive the corresponding injection had significantly poorer outcomes (only tested in the univariate analysis). CONCLUSION: This study confirms the predictors of BCVA score at 1 year posttreatment; the presence of intraretinal fluid was associated with a poor prognosis.

Increasing incidence of melanoma after solid organ transplantation: a retrospective epidemiological study.

The risk of melanoma in organ transplant recipients (OTR) is increased compared with the general population. This retrospective study registered all cases of post-transplant melanoma in kidney, heart, lung, and liver transplant recipients followed in our specialized post-transplant Dermatology Clinic since 1991. The yearly prevalence of melanoma and skin carcinoma between 2000 and 2015 was computed and compared in this population. Based on another cohort of kidney transplant recipients grafted since 2005, adjusted age- and sex-standardized incidence ratio (SIR) was calculated using a renal transplantation registry. In our overall OTR cohort, between 1991 and 2000, five melanomas occurred in 1800 OTRs (0.28%), whereas between 1991 and 2015, 53 melanomas were diagnosed in 49 of 4510 OTR (1.09%), representing a 3.9-fold increase in prevalence after 2000. Remarkably, the prevalence of nonmelanoma skin cancers remained unchanged over this period. Two deaths related to melanoma were recorded with an overall follow-up of 62 months. In our cohort of 1102 renal transplant recipients, the SIR of melanoma was 4.52. Our data suggest that contrasting with nonmelanoma skin cancer, the risk of post-transplant melanoma has considerably increased over the last decade.

Splenectomy Increases Postoperative Complications Following Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Complete cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) is increasingly performed on patients with peritoneal carcinomatosis of various origins. Splenectomy often is required in these patients to achieve complete tumor removal. Although splenectomy has been associated with increased morbidity in many major abdominal surgeries, its effect in patients undergoing CRS + HIPEC is unknown. The purpose of this study was to evaluate the impact of splenectomy during CRS + HIPEC on postoperative outcomes. METHODS: We retrospectively identified 39 patients who underwent CRS + HIPEC with splenectomy during a 3-year study period from a prospective database. We compared them to case controls (CRS + HIPEC without splenectomy) that were matched for the complexity of the procedure. We evaluated the complication rate and outcomes of patients in each group. RESULTS: During the study period, splenectomy was performed in 32 % of patients undergoing CRS + HIPEC procedure. Patients in the splenectomy group experienced more grade 3-4 complications than patients in the control group (59 vs. 35.9 %, p = 0.041) as well as more pulmonary complications (41 vs. 7.7 %, p = 0.0006). Multivariate analysis identified splenectomy as the only predictor of overall major complications (odds ratio = 2.57, 95 % confidence interval = 1.03-6.40). Mortality was similar in both groups. CONCLUSIONS: Splenectomy increases major complication rate in patients undergoing CRS + HIPEC and efforts should be made to preserve the spleen during the surgery.