Search

Abstract Background The anesthetic management of parturients with ascending aortic aneurysm for cesarean section can be particularly challenging, primarily because of increased risk for aortic dissection or aneurysm rupture. Case presentation We present some aspects of the anesthetic management of two parturients with ascending aortic aneurysm for cesarean sections; amongst, the use of remifentanil with its effects on patient and newborn. We emphasize the importance of a cardio-obstetric team in the context of preoperative planning of such patients. Also, we reviewed some literature on the anesthetic management with its effect on peri-operative hemodynamic stability. Conclusion Maintaining hemodynamic stability is paramount in the prevention of the rupture or dissection of ascending aortic aneurysm during labor of parturient.

Abstract Background In case of locally advanced and/or non-metastatic unresectable esophageal cancer, definitive chemoradiotherapy (CRT) delivering 50 Gy in 25 daily fractions in combination with platinum-based regimen remains the standard of care resulting in a 2-year disease-free survival of 25% which deserves to be associated with new systemic strategies. In recent years, several immune checkpoint inhibitors (anti-PD1/anti-PD-L1, anti-Program-Death 1/anti-Program-Death ligand 1) have been approved for the treatment of various solid malignancies including metastatic esophageal cancer. As such, we hypothesized that the addition of an anti-PD-L1 to CRT would provide clinical benefit for patients with locally advanced oesophageal cancer. To assess the efficacy of the anti-PD-L1 durvalumab in combination with CRT and then as maintenance therapy we designed the randomized phase II ARION (Association of Radiochemotherapy with Immunotherapy in unresectable Oesophageal carciNoma- UCGI 33/PRODIGE 67). Methods ARION is a multicenter, open-label, randomized, comparative phase II trial. Patients are randomly assigned in a 1:1 ratio in each arm with a stratification according to tumor stage, histology and centre. Experimental arm relies on CRT with 50 Gy in 25 daily fractions in combination with FOLFOX regimen administrated during and after radiotherapy every two weeks for a total of 6 cycles and durvalumab starting with CRT for a total of 12 infusions. Standard arm is CRT alone. Use of Intensity Modulated radiotherapy is mandatory. The primary endpoint is to increase progression-free survival at 12 months from 50 to 68% (HR = 0.55) (power 90%; one-sided alpha-risk, 10%). Progression will be defined with central external review of imaging. Ancillary studies are planned PD-L1 Combined Positivity Score on carcinoma cells and stromal immune cells of diagnostic biopsy specimen will be correlated to disease free survival. The study of gut microbiota will aim to determine if baseline intestinal bacteria correlates with tumor response. Proteomic analysis on blood samples will compare long-term responder after CRT with durvalumab to non-responder to identify biomarkers. Conclusion Results of the present study will be of great importance to evaluate the impact of immunotherapy in combination with CRT and decipher immune response in this unmet need clinical situation. Trial registration ClinicalTrials.gov, NCT: 03777813.Trial registration date: 5th December 2018.

Abstract Background Rheumatic heart disease (RHD) remains the leading cause of cardiac-related deaths and disability in children and young adults worldwide. In The Gambia, the RHD burden is thought to be high although no data are available and no control programme is yet implemented. We conducted a pilot study to generate baseline data on the clinical and valvular characteristics of RHD patients at first presentation, adherence to penicillin prophylaxis and the evolution of lesions over time. Methods All patients registered with acute rheumatic fever (ARF) or RHD at two Gambian referral hospitals were invited for a clinical review that included echocardiography. In addition, patients were interviewed about potential risk factors, disease history, and treatment adherence. All clinical and echocardiography information at first presentation and during follow-up was retrieved from medical records. Results Among 255 registered RHD patients, 35 had died, 127 were examined, and 111 confirmed RHD patients were enrolled, 64% of them females. The case fatality rate in 2017 was estimated at 19.6%. At first presentation, median age was 13 years (IQR [9; 18]), 57% patients had late stage heart failure, and 84.1% a pathological heart murmur. Although 53.2% of them reported history of recurrent sore throat, only 32.2% of them had sought medical treatment. A history suggestive of ARF was reported by 48.7% patients out of whom only 15.8% were adequately treated. Two third of the patients (65.5%) to whom it was prescribed were fully adherent to penicillin prophylaxis. Progressive worsening and repeated hospitalisation was experienced by 46.8% of the patients. 17 patients had cardiac surgery, but they represented only 18.1% of the 94 patients estimated eligible for cardiac surgery. Conclusion This study highlights for the first time in The Gambia the devastating consequences of RHD on the health of adolescents and young adults. Our findings suggest a high burden of disease that remains largely undetected and without appropriate secondary prophylaxis. There is a need for the urgent implementation of an effective national RHD control programto decrease the unacceptably high mortality rate, improve case detection and management, and increase community awareness of this disease.

Abstract Background Intramedullary metastasis (IMM) is a rare disease with poor prognosis. The incidence of IMMs has increased, which has been linked to improved systemic treatment in many cancers. Surgery and/or radiotherapy are the most commonly used treatments; only small-sample retrospective studies and case reports on stereotactic body radiotherapy (SBRT) have reported acceptable results in terms of local control and clinical improvement, with no reported toxicity. Thus, we performed this monocentric retrospective study on five cases treated with SBRT for IMMs, which we supplemented with a systematic review of the literature. Methods We included all patients treated for IMM with SBRT. The target tumor volume, progression-free survival, prescription patterns in SBRT, survival without neurological deficit, neurological functional improvement after treatment, and overall survival were determined. Results: Five patients treated with a median dose of 30 Gy in a median number of fractions of 5 (prescribed at a median isodose of 86%) included. The median follow-up duration was 23 months. Two patients showed clinical improvement. Three patients remained stable. Radiologically, 25% of patients had complete response and 50% had stable disease. No significant treatment-related toxicity was observed. Conclusion: SBRT appears to be a safe, effective, and rapid treatment option for palliative patients.

Abstract Purpose Early stage Merkel cell carcinoma (MCC) is a rare and aggressive primary skin cancer. The standard of care for MCC is broad excision and adjuvant external beam radiation therapy (EBRT). However, for some patients, anesthesia is contraindicated, while others run the risk of serious aesthetic sequelae. In such cases, exclusive radiotherapy is an interesting alternative to surgery. Though limited data is available, this study evaluates exclusive radiotherapy for MCC, using data from the largest retrospective study to date. Methods All patients who were followed in our center between 1989 and 2019 for histologically proven early stage MCC were included in the study. They were treated either by surgery with a 2-cm clear margin followed by adjuvant radiotherapy (RT) or by exclusive RT. Survival rates with adjuvant and exclusive EBRT were analyzed using Cox model and Fine and Gray model depending on the type of survival. p value

Abstract Background Although South Africa (SA) is facing a high prevalence of HIV infection, there is no literature from this region on a link between Bell’s palsy and HIV. The aim of this study was to identify the occurrence of Bell’s palsy in relation to demographics, seasons and HIV status among black South Africans. Methods This retrospective cohort was conducted among adult black patients, without Bell’s palsy in 2003, presenting to the neurology outpatients department at Dr. George Mukhari Academic hospital, Pretoria, South Africa, between 2004 (study baseline) and 2012 (end test). Gender, age, HIV status, and seasons were potential predictors of Bell’s palsy using Cox regression model and Kaplan Meier curves. Results From the baseline of 1487 patients, 20.9% (n = 311) experienced Bell’s palsy onset by the end of the study. In univariate analysis, male gender (RR = 2.1 95% CI 1.7–2.5; P

Abstract Background The evaluation process of French medical students will evolve in the next few years in order to improve assessment validity. Script concordance testing (SCT) offers the possibility to assess medical knowledge alongside clinical reasoning under conditions of uncertainty. In this study, we aimed at comparing the SCT scores of a large cohort of undergraduate medical students, according to the experience level of the reference panel. Methods In 2019, the authors developed a 30-item SCT and sent it to experts with varying levels of experience. Data analysis included score comparisons with paired Wilcoxon rank sum tests and concordance analysis with Bland & Altman plots. Results A panel of 75 experts was divided into three groups: 31 residents, 21 non-experienced physicians (NEP) and 23 experienced physicians (EP). Among each group, random samples of N = 20, 15 and 10 were selected. A total of 985 students from nine different medical schools participated in the SCT examination. No matter the size of the panel (N = 20, 15 or 10), students’ SCT scores were lower with the NEP group when compared to the resident panel (median score 67.1 vs 69.1, p

Abstract Background In Moyamoya Angioplasty (MMA), increased apparent diffusion coefficient (ADC) in frontal white matter (WM) with a normal appearance has been associated with frontal hypoperfusion and executive dysfunction. Multiple burr-hole surgery enables the revascularization of large frontal areas. Goal: To assess the effect of multiple burr-hole surgery on the ADC and cognitive functions in adults with MMA. Methods ADC was measured in 26 brain hemispheres of 14 consecutive adults with MMA (9 women, mean age ± SD: 38.1 ± 10.7 years) prior to and 6 months after burr-hole surgery. ADC was obtained from regions of interest located in frontal and posterior (temporo-occipital) normal-appearing WM. Ten patients had neuropsychological assessment that focused on executive and attentional functions before and after surgery. Results Anterior and posterior ADC values did not differ before surgery (815.8 ± 60.1 vs. 812.1 ± 35.3 mm2/s, p = 0.88). After surgery, frontal ADC was lower than prior to surgery (789.9 ± 64.5 vs. 815.8 ± 60.1 mm2/s; p

Abstract Background Successful delivery of cell-based therapeutics into patients is compromised by their short shelf-life upon release from production facilities due to the living nature of the active component that rapidly loses viability, and therefore its properties. In this context, the use of appropriate additives may contribute to the stabilisation of the cellular component within specifications for a longer time until administration. Results In the present study, we evaluated the effect of different formulations on the stability of viability, identity, and potency of clinical grade multipotent mesenchymal stromal cells in suspension, both electrolyte solution and protein content were found to impact on their shelf-life. Particularly cryopreservation of cells in a Plasmalyte 148 supplemented with 2% (w/v) AlbIX (a yeast-derived recombinant albumin) and 10% (v/v) dimethyl sulfoxide, and final formulation post-thawing in Plasmalyte 148 supplemented with 2% (w/v) AlbIX enabling prolonged stability from 24 h up to 72 h in optimal conditions. Further investigation on the mechanisms of action involved revealed a delay of apoptosis progression into late stage when AlbIX was present. Conclusions The use of optimal formulations for each cell type of interest is crucial to extend the shelf life of cell-based pharmaceuticals and contribute to solve logistical challenges. We demonstrated that the use of Plasmalyte 148 supplemented with 2% (w/v) AlbIX resulted in superior stability of multipotent mesenchymal stromal cells without affecting their identity and multipotency.

Abstract For years, sufficient progress has been made in treating heart failure following myocardial infarction; however, the social and economic burdens and the costs to world health systems remain high. Moreover, treatment advances have not resolved the underlying problem of functional heart tissue loss. In this field of research, for years we have actively explored innovative biotherapies for cardiac repair. Here, we present a general, critical overview of our experience in using mesenchymal stem cells, derived from cardiac adipose tissue and umbilical cord blood, in a variety of cell therapy and tissue engineering approaches. We also include the latest advances and future challenges, including good manufacturing practice and regulatory issues. Finally, we evaluate whether recent approaches hold potential for reliable translation to clinical trials.

Abstract Purpose Robotic Stereotactic Body Radiation Therapy with real-time tumor tracking has shown encouraging results for hepatic tumors with good efficacy and low toxicity. We studied the factors associated with local control of primary or secondary hepatic lesions post-SBRT. Methods and materials Since 2007, 153 stereotactic liver treatments were administered to 120 patients using the CyberKnife® System. Ninety-nine liver metastases (72 patients), 48 hepatocellular carcinomas (42 patients), and six cholangiocarcinomas were treated. On average, three to four sessions were delivered over 12 days. Twenty-seven to 45 Gy was prescribed to the 80% isodose line. Margins consisted of 5 to 10 mm for clinical target volume (CTV) and 3 mm for planning target volume (PTV). Results Median size was 33 mm (range, 5–112 mm). Median gross tumor volume (GTV) was 32.38 cm3 (range, 0.2–499.5 cm3). Median total dose was 45 Gy in three fractions. Median minimum dose was 27 Gy in three fractions. With a median follow-up of 15.0 months, local control rates at one and two years were 84% and 74.6%, respectively. The factors associated with better local control were lesion size Conclusions Dose, tumor diameter and volume are prognostic factors for local control when a stereotactic radiation therapy for hepatic lesions is considered. These results should be considered in order to obtain a maximum therapeutic efficacy.

Abstract Purpose The purpose of this study is to evaluate the feasibility, efficacy and toxicity of SBRT for treatment of unresectable hepatic or lung metastases regardless of their primary tumor site for patients who received prior systemic chemotherapy. Methods and materials Between July 2007 and June 2010, 90 patients were treated with the CyberKnife® SBRT system for hepatic or pulmonary metastatic lesions. Medical records were retrospectively reviewed. The endpoints of this study were local control, overall survival (OS), disease-free survival (DFS), local relapse free-survival (LRFS), and treatment toxicity. Results A total of 113 liver and 26 lung metastatic lesions in 52 men (58%) and 38 women (42%) were treated. Median follow-up was 17 months. Median age at treatment was 65 years (range, 23–84 years). Primary cancers were 63 GI, three lung, eight breast, four melanoma, three neuro-endocrine tumors, and three sarcomas. Median diameter of the lesions was 28 mm (range, 7–110 mm) for liver and 12.5 mm (range, 5–63.5 mm) for lung. Local control rates at 1 and 2 years were 84.5% and 66.1%, respectively. Two-year overall survival rate was 70% (95% CI: 55–81%). The 1 and 2-year disease-free survival rates were 27% (95% CI: 18–37%) and 10% (95% CI: 4–20%), respectively. Median duration of disease-free survival was 6.7 months (95% CI: 5.1–9.5 months). Observed toxicities included grade 1–3 acute toxicities. One grade 3 and no grade 4 toxicity were reported. Conclusion High-dose SBRT for metastatic lesions is both feasible and effective with high local control rates. Overall survival is comparable with other available techniques. Treatment is well tolerated with low toxicity rates. It could represent an interesting treatment option for oligometastatic patients not amenable to surgery, even when patients had been pre-treated with chemotherapy. Summary Stereotactic body radiotherapy (SBRT) has previously been successfully used in the treatment of metastatic lesions. It could be considered as a curative option for oligometastatic patients. This retrospective study involved 90 patients, designed to test potential effectiveness of SBRT in the treatment of oligometastases irrespective of primary. Results suggest SBRT could be an effective treatment extending patients’ life span. This treatment appears to be more effective when used prior to multiple systemic treatment regimens.

Abstract Purpose Stereotactic body radiation therapy (SBRT) for early-stage lung cancer can be achieved with several methods: respiratory gating, body frame, or real-time target and motion tracking. Two target tracking methods are currently available with the CyberKnife® System: the first one, fiducial tracking, requires the use of radio-opaque markers implanted near or inside the tumor, while the other, Xsight® Lung Tracking System, (XLTS) is fiducial-free. With XLTS, targeting is synchronized directly with target motion, which occurs due to respiration. While the former method (fiducial tracking) is well documented, the clinical relevance of the latter (tracking without fiducials) has never been well described to this date. Patients and Methods A study was performed at our department for each patient treated for lung cancer with CyberKnife using XLTS. Selection criteria were: primary or recurring T1 or T2 stage non-small-cell lung cancer (NSCLC) with 15–60 mm tumor size. Initial staging included CT-Scan and FDG-PET. Results Fifty-one patients not amenable to surgery were treated with XLTS. Median follow-up was 15 months (range, 5–30 months). Median tumor size was 24 mm (range, 15–60 mm). Median total dose was 60 Gy (36–60 Gy) in three fractions. Actuarial overall survival was 85.5% (95% CI = 74.5–96%) at 1 year and 79.4% (95% CI = 64–94.8%) at 2 years. Actuarial local control rate was 92% (95% CI = 84–99%) at one1 year and 86% (95% CI = 75–97%) at 2 years. Conclusion Local control and overall survival rates were similar to previous reports that used fiducials for tumor tracking. Toxicity was lower than most studies since tumor tracking did not require fiducial implantion. This fiducial-free method for respiratory motion tracking is a valid option for the most fragile patients.

Abstract Background The first-line treatment of a pelvic recurrence in a previously irradiated area is surgery. Unfortunately, few patients are deemed operable, often due to the location of the recurrence, usually too close to the iliac vessels, or the associated surgical morbidity. The objective of this study is to test the viability of robotic image-guided radiotherapy as an alternative treatment in inoperable cases. Methods Sixteen patients previously treated with radiotherapy were reirradiated with CyberKnife® for lateral pelvic lesions. Recurrences of primary rectal cancer (4 patients), anal canal (6), uterine cervix cancer (4), endometrial cancer (1), and bladder carcinoma (1) were treated. The median dose of the previous treatment was 45 Gy (EqD2 range: 20 to 96 Gy). A total dose of 36 Gy in six fractions was delivered with the CyberKnife over three weeks. The responses were evaluated according to RECIST criteria. Results Median follow-up was 10.6 months (1.9 to 20.5 months). The actuarial local control rate was 51.4% at one year. Median disease-free survival was 8.3 months after CyberKnife treatment. The actuarial one-year survival rate was 46%. Acute tolerance was limited to digestive grade 1 and 2 toxicities. Conclusions Robotic stereotactic radiotherapy can offer a short and well-tolerated treatment for lateral pelvic recurrences in previously irradiated areas in patients otherwise not treatable. Efficacy and toxicity need to be evaluated over the long term, but initial results are encouraging.

Abstract Purpose To analyze the outcome after adjuvant radiation therapy with standard fractionation regimen in metastatic lymph nodes (LN) from cutaneous melanoma. Patients and methods 86 successive patients (57 men) were treated for locally advanced melanoma in our institution. 60 patients (69%) underwent LN dissection followed by radiation therapy (RT), while 26 patients (31%) had no radiotherapy. Results The median number of resected LN was 12 (1 to 36) with 2 metastases (1 to 28). Median survival after the first relapse was 31.8 months. Extracapsular extension was a significant prognostic factor for regional control (p = 0.019). Median total dose was 50 Gy (30 to 70 Gy). A standard fractionation regimen was used (2 Gy/fraction). Median number of fractions was 25 (10 to 44 fractions). Patients were treated with five fractions/week. Patients with extracapsular extension treated with surgery followed by RT (total dose ≥50 Gy) had a better regional control than patients treated by surgery followed by RT with a total dose Conclusion Adjuvant radiotherapy was able to increase regional control in targeted sub-population (LN with extracapsular extension).