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Summary Introduction Anastomotic fistula is the most fearsome complication following colorectal surgery. Numerous studies have demonstrated the interest of postoperative CRP assay as an early diagnostic marker. Must the critical threshold for biological inflammatory markers remain the same, whether resection be colic or rectal? Patients and method This is a study based on a cohort constituted between 2011 and 2014, including 497 patients with planned colorectal resection. C-reactive protein and pro-calcitonin were measured daily from day before surgery to D4. All postoperative intra-abdominal complications were considered as an anastomotic fistula. Detection thresholds were calculated from the area under the ROC curve. Results An intra-abdominal septic complication occurred in 16.9% of the patients having undergone rectal resection vs. 9.9% of those having had colectomy (P = 0.03). In the absence of complications there was no significant difference between the two groups in terms of postoperative inflammatory response as determined by either CRP or PCT assay. Following rectal resection, optimal area under the curve (AUC = 0.87) corresponds to CRP on D4 for a threshold of 100 mg/L: sensitivity 83.3%, NPV 95.3%. For colons with the same CRP at 100 mg/L (AUC = 0.71): sensitivity 63.6%, NPV 93.9%. Conclusion Notwithstanding riskier surgery, the detection threshold for an anastomotic fistula following rectal surgery remains the same: CRP > 100 mg/L at D4.

BACKGROUND: Adjuvant chemotherapy (AC) is recommended since 2004 for patients with a completely resected non-small cell lung cancer (NSCLC). Indeed, several randomized clinical trials have demonstrated an improved survival for patients treated with adjuvant cisplatin-based regimen than surgery alone. In these large clinical trials, patients were well selected and fit to receive AC. As the benefit of AC was estimated at 5.4% of 5-year overall survival (OS), it seems important to evaluate AC use in a less selected population. In particular, elderly patients were underrepresented in large randomized clinical trials. Furthermore, other confounding factors might limit AC efficacy in real-life practice such as the delay of chemotherapy initiation following lung surgery or the number of AC cycles received. Therefore, the aim of this systematic review is to summarize the state of the literature on AC use in current clinical practice. METHODS: A systematic assessment of literature articles and reviews on AC use in real-life practice was performed by searching in several relevant database including Medline, Google Scholar and Cochrane Library following PICOS (i.e., Population, Intervention, Comparison, Outcomes, Study design) eligibility criteria and PRISMA guidelines. Among the 1,957 results obtained with the request formulated on these research database, 56 relevant articles on AC use in non-trial setting were selected and included in the results section. RESULTS: This systematic literature review highlights the lack of literature on AC use in real-life practice as most of these studies were retrospective. Interestingly, a delayed AC—mostly due to postoperative complications—was better than surgery alone. Furthermore, AC was less purposed to elderly patients, despite retrospective studies outlined that this therapeutic option could be benefit in this specific population as for younger patients. In real-life practice, AC was also often incomplete due to adverse events, but dose reduction or omission was not always associated with an inferior survival. In non-trial setting, number of AC cycles delivered, dose reduction or omission is quite similar to randomized clinical trials. DISCUSSION: Nowadays, AC is part of the therapeutic strategy used in completely resected NSCLC. In a population of less selected patients, this systematic literature review shows that AC can be used safely and efficiently, especially in elderly patients. As well, delayed AC seems effective. Finally, the place of immunotherapy and targeted therapies have to be precised in the future as well as biomarkers to better select patients that would response to chemotherapy.

The prognostic impact of tumour grading, cytological and architectural patterns and stromal features in diffuse pleural malignant epithelioid mesothelioma (MEM) has been partly studied but not correlated to molecular features. We performed a retrospective study on 92 MEM in our department in order to assess the prognostic role of architectural and stromal patterns, especially tumour to stroma ratio. Secondly, based on The Cancer Genome Atlas (TCGA) database, we analysed the differentially expressed genes in prognostic groups of interest. Our results showed that tumour grading, tumour to stroma ratio and predominant pattern were related to overall survival, p≤0.001, p=0.01 and p=0.001, respectively. In univariate analysis, for high grade tumours hazard ratio (HR) was 4.75 (2.47-9.16), for stroma poor tumours HR=0.016, for predominant tubular or tubulopapillary pattern HR=0.044. In multivariate analysis, high grade tumours were related to overall survival [HR=3.09 (1.50-6.35), p=0.002] and predominant tubular or tubulopapillary pattern [HR=0.56 (0.32-0.99), p=0.045]. In TCGA analysis, after grading of diagnostic slides, we showed that KRTDAP and CXRCR1 expression was higher in low grade tumours, unlike PDZD7 and GPR176 expression which was higher in high grade tumours. FAM81B had a higher expression in stroma poor tumours. We did not find any differentially expressed genes in the architectural patterns group. Our work suggests that tumour grading is an important parameter in MEM with an underlying genomic basis. The role of tumour to stroma ratio needs to be investigated and might also have a genomic basis.

Diffuse Idiopathic Pulmonary NeuroEndocrine Cell Hyperplasia (DIPNECH) is a rare disease often associated with carcinoid tumors. We aimed at evaluating the impact of DIPNECH on characteristics and prognosis of patients who underwent radical treatment of pulmonary carcinoid tumors.We reviewed all patients operated on for curative-intent resection of carcinoid tumor in our department from 2001 to 2020. Cases exhibiting both pathological and radiological features of DIPNECH, as assessed by respective thoracic expert physicians, were analyzed separately.172 cases of resected carcinoid tumors were identified, including 25 (14.5 %) harboring pathological criteria of DIPNECH and radiologic features like mosaic attenuation (92.0 %), multiple nodules5 mm (76.0 %), and mucoid impactions (32 %). In DIPNECH patients, major pulmonary resections were usually performed (92.0 %) and resected tumors were mostly classified as pT1 (92 %). Mean Ki67 staining was 3.7 ± 5.2 %. The early postoperative period was mostly uneventful (96.0 %) and 5-year survival was 92.9 ± 6.9 %. Compared to non-DIPNECH cases, we found that patients were older (mean 65.6 ± 9.3 versus 54.1 ± 17.9, p = 0.002), more frequently female (84.0 % versus 56.5 %, p = 0.009), and exhibiting diabetes mellitus (45.8 % versus 18.5 %, p 0.001) or hypertension (45.8 % versus 24.1 %, p = 0.039). The rate of atypical carcinoid tumors was significantly higher in DIPNECH patients (40.0 % versus 19.9 %, p = 0.027), as well as rate of mediastinal lymph-nodes involvement (pN2+) (36.0 % versus 4.1 %, p 0.001). At multivariate analysis, only DIPNECH pattern and atypical histology were independent factors of pN2 invasion which was the only predictor of poorer prognosis on Log-Rank test.Carcinoid tumors with proven DIPNECH are associated with negative pathological features and may deserve a dedicated perioperative management.

Summary Objective This pragmatic, multicenter, open-label, randomized controlled trial (RCT) aimed to compare the effectiveness, safety, and cost–utility of a custom-made knee brace versus usual care over 1 year in medial knee osteoarthritis (OA). Design 120 patients with medial knee OA (VAS pain at rest >40/100), classified as Kellgren–Lawrence grade II-IV, were randomized into two groups: ODRA plus usual care (ODRA group) and usual care alone (UCA group). The primary effectiveness outcome was the change in VAS pain between M0 and M12. Secondary outcomes included changes over 1 year in KOOS (function) and OAKHQOL (quality of life) scores. Drug consumption, compliance, safety of the knee brace, and cost–utility over 1 year were also assessed. Results The ODRA group was associated with a higher improvement in: VAS pain (adjusted mean difference of −11.8; 95% CI: −21.1 to −2.5); all KOOS subscales (pain: +8.8; 95% CI: 1.4–16.2); other symptoms (+10.4; 95% CI: 2.7–18); function in activities of daily living (+9.2; 95% CI: 1.1–17.2); function in sports and leisure (+12.3; 95% CI: 4.3–20.3); quality of life (+9.9; 95% CI: 0.9–15.9), OAKHQOL subscales (pain: +14.8; 95% CI: 5.0–24.6); and physical activities (+8.2; 95% CI: 0.6–15.8), and with a significant decrease in analgesics consumption at M12 compared with the UCA group. Despite localized side-effects, observance was good at M12 (median: 5.3 h/day). The ODRA group had a more than 85% chance of being cost-effective for a willingness-to-pay threshold of €45 000 per QALY. Conclusions The ERGONOMIE RCT demonstrated significant clinical benefits of an unloader custom-made knee brace in terms of improvements in pain, function, and some aspects of quality of life over 1 year in medial knee OA, as well as its potential cost–utility from a societal perspective.

BackgroundInfection of the pleural cavity invariably leads to hospitalisation, and a fatal outcome is not uncommon. Our aim was to study the epidemiology of pleural empyema on a nationwide basis in the whole population and in three subgroups of patients, namely post-lung resection, associated cancer and those with no surgery and no cancer.MethodsData from patients aged ≥18 years hospitalised with a diagnosis of pleural infection in France between January 2013 and December 2017 were retrieved from the medical-administrative national hospitalisation database and retrospectively analysed. Mortality, length of stay and costs were assessed.ResultsThere were 25 512 hospitalisations for pleural empyema. The annual rate was 7.15 cases per 100 000 habitants in 2013 and increased to 7.75 cases per 100 000 inhabitants in 2017. The mean age of patients was 62.4±15.6 years and 71.7% were men. Post-lung resection, associated cancer and no surgery–no cancer cases accounted for 9.8%, 30.1% and 60.1% of patients, respectively. These groups were significantly different in terms of clinical characteristics, mortality and risk factors for length of stay, costs and mortality. Mortality was 17.1% in the whole population, 29.5% in the associated cancer group, 17.7% in the post-lung resection group and 10.7% in the no surgery–no cancer group. In the whole population, age, presence of fistula, higher Charlson Comorbidity Index (>3), alcohol abuse, arterial hypertension, hyperlipidaemia, atheroma, atrial fibrillation, performance status >3 and three subgroups of pleural empyema independently predicted mortality.ConclusionsEmpyema is increasing in incidence. Factors associated with mortality are recent lung resection and associated diagnosis of cancer.

Objectives: The use of granulocyte colony-stimulating factors (G-CSF) during concurrent chemo-radiotherapy (cCTRT) for small cell lung cancer is not recommended by the American Society of Clinical Oncology due to safety concerns. This secondary analysis explored the safety and the role of prophylactic G-CSF (proG-CSF) in the delivery of cCTRT. Material and methods: Secondary analysis of 487 patients treated as per protocol on the phase 3 CONVERT trial which randomized patients between once-daily RT or twice-daily. Results: 180 of 487 eligible patients (37 %) received proG-CSF, 60 (33 %) as primary prophylaxis and 120 (67 %) as secondary prophylaxis following myelotoxic events. The regimen incidence of febrile neutropenia (FN) was 22 %. Its incidence in the proG-CSF group reduced significantly when proG-CSF was administered (22 % vs 10 %; OR 0.4; 95 %CI 0.2-0.7; p = 0.002). The rate of blood transfusion was higher in the proG-CSF group (51 % vs 31 %; OR 2.4; 95 %CI 1.6-3.5; p < 0.001). The incidence of severe thrombocytopenia was also higher is this group (28 % vs 15 %; OR 2.2; 95 %CI 1.4-3.5; p = 0.001). But this was significantly higher in those on secondary vs primary prophylaxis (34 % vs 15 %; OR 2.9; 95 %CI 1.3-7.4 p = 0.009) No differences observed in RT-related toxicity, treatment-related mortality or any survival outcomes. The optimal dose intensity (85 % or higher) of cisplatin was achieved in more patients within the proG-CSF group (75 % vs 67 %; OR 1.5; 95 %CI 0.9-2.3; p = 0.056). Conclusion: There was no evidence that G-CSF directly caused myelotoxicity, instead most patients started G-CSF due to higher myelotoxicity risk. G-CSF maintained the planned dose intensity and there was no detrimental effect on survival. G-CSF may be considered as a supportive measure in this setting.

BACKGROUND Social deprivation may have a deleterious influence on post-stroke outcomes, but available data in the literature are mixed. AIM The aim of this cohort study was to evaluate the impact of social deprivation on 1-year survival in patients with first-ever stroke. METHODS Social deprivation was assessed at individual level with the EPICES score, a validated multidimensional questionnaire, in 1312 patients with ischemic stroke and 228 patients with spontaneous intracerebral hemorrhage, who were prospectively enrolled in six French study centers. Baseline characteristics including stroke severity and pre-stroke functional status were collected. Multivariable Cox models were generated to evaluate the associations between social deprivation and survival at 12 months in ischemic stroke and intracerebral hemorrhage separately. RESULTS A total of 819 patients (53.2%) were socially deprived (EPICES score ≥ 30.17). In ischemic stroke, mortality at 12 months was higher in deprived than in non-deprived patients (16% vs. 11%, p = 0.006). In multivariable analyses, there was no association between deprivation and death occurring within the first 90 days following ischemic stroke (adjusted hazard ratio [aHR] 0.81, 95% CI 0.54-1.22, p = 0.32). In contrast, an excess in mortality was observed between 90 days and 12 months in deprived compared with non-deprived patients (aHR 1.97, 95% CI 1.14-3.42, p = 0.016). In patients with intracerebral hemorrhage, mortality at 12 months did not significantly differ according to deprivation status. CONCLUSIONS Social deprivation was associated with delayed mortality in ischemic stroke patients only and, although the exact underlying mechanisms are still to be identified, our findings suggest that deprived patients in particular may benefit from an optimization of post-stroke care.

Adapting therapies and providing personalized care for patients with resectable non-small cell lung cancer represent major challenges. This involves integrating several parameters into the patient's management, not only crude pathologic results, but also a better understanding of the mechanisms involved in tumor progression. Many studies have looked at the impact of host and tumor characteristics and their interactions through inflammatory processes or tumor immune environment. Beyond tumor stage, poor nutrition, sarcopenia and inflammatory state have been identified as independent factors that can directly impact postoperative outcome. The development of Enhanced Recovery After Surgery (ERAS), in which patient becomes the main player in their own management, seems to be an interesting answer since it seems to allow a reduction in postoperative complications, length of stay and indirectly reduction in costs. A broader and more complete vision including morphometric evaluation of the patient, physical performances, inflammatory state and nutritional state would provide additional discriminating information which can predict postoperative outcome and help in adapting therapies in a personalized way.

Pretreatment D-dimer levels have been reported to predict survival in several types of malignancies in human patients. The objective of this study was to evaluate the prognostic value of pretreatment D-dimer level in dogs with intermediate to high-grade non-Hodgkin lymphoma (NHL). In a prospective, randomized, double-blind study of F14512 versus etoposide phosphate, we assessed the prognostic value of pretreatment plasma D-dimer level in 48 client-owned dogs diagnosed with intermediate to high-grade NHL. The correlation between pretreatment plasma D-dimer level and various clinical features, progression-free survival (PFS), and overall survival (OS) was analyzed. The median value of pretreatment plasma D-dimer level was 0.4 μg/mL (range: 0.1-14.3 μg/mL). High pretreatment plasma D-dimer level (> 0.5 μg/mL) was detected in 44% (21/48) of dogs. High D-dimer levels were not correlated with naive versus relapsed lymphoma, clinical stage, substage, immunophenotype or treatment group. D-dimer levels > 0.5 μg/mL were significantly associated with inferior median PFS (54 vs. 104 days, P = 0.011) and OS (93 vs. 169 days, P = 0.003). In the multivariate analysis, high D-dimer levels remained an independent predictor for worse PFS (HR: 3.21, 95%-CI: 1.57 – 6.56, P = 0.001) and OS (HR: 3.87, 95%-CI: 1.88 – 7.98; P < 0.001). This study suggests that pretreatment plasma D-dimer level can serve as a predictor of prognosis in dogs with intermediate to high-grade NHL. Further studies are warranted to confirm these findings.

Gastropleural and gastrobronchial fistulas (GPF/GBFs) are serious but rare complications after bariatric surgery whose management is not consensual. The aim was to establish a cohort and evaluate different clinical presentations and therapeutic options. A multicenter and retrospective study analyzing GPF/GBFs after bariatric surgery in France between 2007 and 2018, via a questionnaire sent to digestive and thoracic surgery departments. The study included 24 patients from 9 surgical departments after initial bariatric surgery (21 sleeve gastrectomies; 3 gastric bypass) for morbid obesity (mean BMI = 42 ± 8 kg/m2). The GPF/GBFs occurred, on average, 124 days after bariatric surgery, complicating an initial post-operative gastric fistula (POGF) in 66% of cases. Endoscopic digestive treatment was performed in 79% of cases (n = 19) associated in 25% of cases (n = 6) with thoracic endoscopy. Surgical treatment was performed in 83% of cases (n = 20): thoracic surgery (n = 5), digestive surgery (n = 8), and combined surgery (n = 7). No patient died. Overall morbidity was 42%. The overall success rate of the initial and secondary strategies was 58.5% and 90%, respectively. The average healing time was approximately 7 months. Patients who had undergone thoracic surgery (n = 12) had more initial management failures (n = 9/12) than patients who had not (n = 3/12), p = 0.001. Complex and life-threatening fistulas that are revealed late require a multidisciplinary strategy. Thoracic surgery should be reserved once the abdominal leak heals; otherwise, it is associated with a higher risk of failure.

Severe pulmonary edema, secondary to left ventricular afterload increment, is a common problem occurring in patients receiving venoarterial extracorporeal membrane oxygenation. No consensus is currently available for its management, but several devices/procedures have been described, including an Impella device (Abiomed), balloon atrial septostomy, intraaortic balloon counterpulsation, or an additional venous cannula, as possible adjuncts. We report the feasibility and efficacy of the atrial flow regulator device (Occlutech) for left ventricular unloading in a 58-year-old patient receiving extracorporeal membrane oxygenation. However, the benefits of this device relative to simple balloon atrial septostomy need to be further investigated.

Background Cancer patients are thought to have an increased risk of developing severe Coronavirus Disease 2019 (COVID-19) infection and of dying from the disease. In this work, predictive factors for COVID-19 severity and mortality in cancer patients were investigated. Patients and Methods In this large nationwide retro-prospective cohort study, we collected data on patients with solid tumours and COVID-19 diagnosed between March 1 and June 11, 2020. The primary endpoint was all-cause mortality and COVID-19 severity, defined as admission to an intensive care unit (ICU) and/or mechanical ventilation and/or death, was one of the secondary endpoints. Results From April 4 to June 11, 2020, 1289 patients were analysed. The most frequent cancers were digestive and thoracic. Altogether, 424 (33%) patients had a severe form of COVID-19 and 370 (29%) patients died. In multivariate analysis, independent factors associated with death were male sex (odds ratio 1.73, 95%CI: 1.18-2.52), ECOG PS ≥ 2 (OR 3.23, 95%CI: 2.27-4.61), updated Charlson comorbidity index (OR 1.08, 95%CI: 1.01-1.16) and admission to ICU (OR 3.62, 95%CI 2.14-6.11). The same factors, age along with corticosteroids before COVID-19 diagnosis, and thoracic primary tumour site were independently associated with COVID-19 severity. None of the anticancer treatments administered within the previous 3 months had any effect on mortality or COVID-19 severity, except cytotoxic chemotherapy in the subgroup of patients with detectable SARS-CoV-2 by RT-PCR, which was associated with a slight increase of the risk of death (OR 1.53; 95%CI: 1.00-2.34; p = 0.05). A total of 431 (39%) patients had their systemic anticancer treatment interrupted or stopped following diagnosis of COVID-19. Conclusions Mortality and COVID-19 severity in cancer patients are high and are associated with general characteristics of patients. We found no deleterious effects of recent anticancer treatments, except for cytotoxic chemotherapy in the RT-PCR-confirmed subgroup of patients. In almost 40% of patients, the systemic anticancer therapy was interrupted or stopped after COVID-19 diagnosis., Highlights • A total of 1289 patients with solid tumours and COVID-19 were analysed. • Mortality and COVID-19 severity were mainly driven by patient general characteristics. • Overall, we found no deleterious effects of recent anticancer treatments on mortality. . • Systemic anticancer treatment was interrupted or stopped in 39% of patients.

Background While its importance in daily living, the anaerobic metabolism is not taken into account in clinical practice. The lack of validated functional performance tests for patients with chronic disabilities may explain this defect. In this context, the Short and Fast Step Test (SFST) was recently developed and validated in healthy volunteers. Aim The purpose of this study was to investigate the safety, feasibility and reliability of the SFST, a functional test exploring anaerobic metabolism in coronary patients during cardiac rehabilitation. Design This study was a monocentric prospective study. Settings This study took place in the rehabilitation center of the University Hospital Center of Dijon, France. Population 44 coronary patients, addressed for a first cardiac rehabilitation, were included in this protocol. Methods All participants performed three SFST: T1 and T2 (including respiratory gas exchange) the first day of the program and T3 after 3 to 7 days. SFST consists of walking up and down a 17.5cm-high step as many times as possible in 1 minute. Safety was assessed by the percentage of patients who performed the SFST without reporting a fall, or muscular or cardiovascular events. Feasibility was evaluated by the percentage of patients who succeeded in doing the SFST. Reliability was assessed with the number of raised steps in same condition (T1-T3) and different conditions (T1-T2) using a 2-way intraclass correlation coefficient (ICC). Values were given with their 90% confidence interval [90%CI]. Results The safety was 95.2% [85.8;99.2] for T1, 88.1% [76.6;95.2] for T2 and 90.4% [79.5;96.7] for T3. 100% [93,1;100] of participants completed T1 and T2, 92.9% [82.6;98] T3. An ICC of 0.74 [0.60;0.84] was observed between T1 and T3 and of 0.87 [0.79;0.92] between T1 and T2. Conclusions This study demonstrates the good safety, feasibility and reliability of the SFST to assess anaerobic metabolism in coronary patients in a rehabilitation program. Clinical rehabilitation impact These results show that the SFST seems suitable for the evaluation of brief submaximal functional capacity in daily activities. It offers a real possibility to assess such capacity during the cardiac rehabilitation routine.

Background French Guiana has the highest incidence of ischemic and hemorrhagic stroke of all French territories. However, there is no further information on the epidemiology and management of stroke in French Guiana. Our goal was to describe the characteristics of patients in French Guiana in order to generate hypotheses regarding the determinants explaining the magnitude of this public health problem. Methods We used the data of the French multicentre INDIA prospective cohort study which included consecutive patients aged > 18 years with a first-ever stroke from June 2011 to October 2014. For the present study, only patients with ischemic or hemorrhagic stroke admitted in one of the 3 participating hospitals were analyzed. Results Among the 298 patients (mean age 62.2 ± 14.5 years, 63.7% man) included in French Guiana, 52% were born abroad. Most strokes were ischemic strokes (79%), 14% of which were thrombolyzed. Hypertension (70.2%), history of smoking (22%) and diabetes (25%) were the most common risk factors and 28.4% of patients had known but untreated hypertension. Overall 89 (38%) patients with ischemic stroke were admitted less than 4.5 h after the first symptoms. In-hospital mortality was greater for intracerebral hemorrhage (18.7%) than for ischemic stroke (4.2%). Overall, 84.5% had health insurance coverage and among these, 41.9% had CMU, the universal health insurance for the poor. Conclusions The present study is the first epidemiologic description of stroke in French Guiana. The comparisons of these results show that stroke patients in French Guiana are epidemiologically atypical because they are younger, and more likely to be males than patients in mainland France. Stroke risk factors and delay between stroke and hospital admission were comparable with what is observed in France, suggesting that efforts should focus on primary care and social inequalities of health to alleviate the main determinants of stroke in French Guiana.

A 75-year-old female patient, nonsmoker was addressed to our institution for a fracture of C5 vertebra with spinal cord compression by a tumor mass invading surrounding soft tissue. She had a previous history of breast ductal carcinoma and endometrioid carcinoma. Biopsy of the tumor mass showed a TTF-1-positive carcinoma. Molecular study showed a E545K mutation of PIK3CA. Lung imaging showed multiple nodules evocative of metastasis rather than a primitive tumor. Reviewing of slides of endometrioid carcinoma showed areas positive for TTF1, and the same E545K mutation was found in endometrial tumor. The final diagnosis was endometrioid metastatic carcinoma with aberrant TTF-1 expression. A subset of endometrial neoplasm expresses TTF-1, this situation might be confusing especially in case of metastatic disease.

Summary Background Testicular Germ Cell Tumors (TGCTs) represent the most frequent malignant tumour among young male adults. Orchiectomy alone cure 80% of stage I. Standard options after orchiectomy include radiotherapy (RT), chemotherapy (CT) by 1 cycle of carboplatin AUC 7 or active surveillance (SV) for seminomatous GCTs (SGCT) and retroperitoneal lymphadenectomy (RPLND), CT by 1 or 2 cycles of Bleomycine Etoposide Cisplatine (BEP) or active surveillance for nonseminomatous GCTs (NSGCT). Adjuvant treatments decrease the relapse rate after orchiectomy with substantial toxicities without any benefit on overall survival. Recent guidelines accorded utmost importance on SV rather than adjuvants strategies. The main objective of this study was to describe our current practice over the 10 past years in regard of these recommendations. Methods Data of 50 patients with stage I GCT treated in our institute were collected between 2006 and 2016. Demographic and anatomopathologic data were reported. Clinical practice in our center was analyzed during two periods [2006–2011] and [2012–2016] according to the European Association of Urology Guidelines in 2011. Results Patient's median age was 35.3 years. The analysis of clinical practice during the last 10 years showed that in SGCT, main treatment was RT than SV and CT. This option declined over the years (89% between 2006–2010 versus 53% between 2011–2016) whereas SV was more often employed (27% between 2011-2016 versus none between 2006–2010). Surveillance was used for 64% of NSGCT. Conclusions In our center, RT was less used over the years for the benefit of SV which is recommended by guidelines.

Background Vertebral involvement by a thoracic tumor has long been considered as a limit to surgical treatment, and despite advances, such an invasive operation remains controversial. The aim of this study was to characterize a single-center cohort and to evaluate the outcome, focusing on survival and complications. Methods We retrospectively reviewed the data of all patients operated on for tumors involving the thoracic spine in an 8-year period. En bloc resection was generally performed by a double team involving thoracic and orthopedic surgeons. Distant follow-up was recorded for oncologic and functional analysis. Results There were 31 patients operated on. An induction therapy was administered in 20 patients. Spinal resection (mostly including ≥2 vertebral levels) was combined with lobectomy in 48.3% of the patients, and osteosynthesis was required in 22 patients. We observed no in-hospital death and a major complications rate of 32.3%, including 5 patients with early neurologic complications. There were 61.3% primary lung carcinomas, 12.9% extrapulmonary primaries, 9.7% metastases, and 16.1% benign tumors. Mean follow-up was 32.1 months. The 5-year overall survival rate was 81.3% in the entire cohort and 75.0% in patients with a malignant tumor. Occurrence of an early postoperative major complication was the only factor significantly associated with shorter overall survival (p = 0.03). The 5-year disease-free survival rate was 37.0% in malignancies. Delayed complications occurred in 35.5% of patients, including persistent neurologic deficit in 12.9%, instrumentation migration in 19.4%, and local infection in 12.9%. Conclusions En bloc resection of spinal thoracic tumors offers long-term survival and few recurrences in highly selected patients but is associated with significant delayed mechanical or infectious complications.

Aim: We performed a clinical audit of the management of patients with EGFR mutations, 1 year after the introduction of EGFR tyrosine kinase inhibitor ( EGFR-TKI) in first-line treatment. Methods: Compliance was defined by tumor molecular profiling for stage IIIB and IV non-small-cell lung cancer and first-line treatment as recommended by the French guidelines. Results: Among the 169 EGFR-mutated patients, compliance was 76.4%. The most common noncompliance criterion was chemotherapy given in first-line treatment instead of EGFR-TKI. No dedicated multidisciplinary meeting and type of institutions were independent unfavorable predictors for compliance. Compliance to guidelines was significantly correlated with time-to-first subsequent treatment improvement (2.5 vs 9.1 months; p

The resistance mutation T790M is reported in 50–60% of patients pretreated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). Osimertinib has been approved in these patients, but data in octogenarians remain rare. The objective of this retrospective analysis was to evaluate in real life the efficacy of osimertinib in a population of octogenarian patients. This retrospective multicentric study included pretreated octogenarian patients with EGFR T790M-mutated advanced non-small cell lung cancer (NSCLC) in the setting of the French early access program for osimertinib. The primary endpoints were progression-free survival (PFS) and overall survival (OS) from osimertinib initiation. In total, 43 patients were included (mean age 84.6 years; women 90.7%: adenocarcinoma 100%; never smokers 90.5%; at osimertinib initiation: performance status ≥ 2, 42.4%; stage 4, 93.0%; brain metastases 16.3%). Patients received a median of two lines of treatment before osimertinib initiation, and all received first- or second-generation EGFR TKIs before osimertinib (first line in 79.1%). Osimertinib was used as a second-line treatment in 41.9% of cases and third line or more in 58.1%. Median PFS was 17.5 (95% confidence interval [CI] 12.2–19.0) months for the entire population: 20.6 (95% CI 18.8–not reached) months in patients with brain metastases and 16.7 (95% CI 10.4–18.9) months in patients without (p = 0.1). There was no significant difference for osimertinib treatment as second or third line or more (17.1 vs. 18.6 months, respectively). OS was 22.8 (95% CI 15.7–not reached) months from osimertinib initiation. The efficacy of osimertinib as second-line treatment or more in octogenarian pretreated patients with EGFR T790M-mutated advanced NSCLC in a real-life setting was similar to that in randomized controlled trials.

Concomitant radiochemotherapy (RTCT) is the standard treatment for unresectable stage III non-small cell lung cancer (NSCLC). However, in patients with a peripheral primary tumor, the irradiated volume may include a large portion of normal lung and RT-CT is not possible. This multicenter phase II trial in unresectable stage III NSCLC with peripheral primary tumor evaluated the feasibility of stereotactic body radiation therapy (SBRT) in peripheral tumor after concomitant radio-chemotherapy (RT-CT). Nineteen patients were included and analyzed (median age, 60.9 years, male, 78%, adenocarcinoma, 74%, median size of peripheral primary tumor, 19 mm). At 6 months, the disease control rate was 79% (15/19). SBRT toxicity was generally mild with one (5%) patient having grade 3 lung toxicity. Recruitment for this study was stopped prior to completion, firstly due to the approval of adjuvant durvalumab after RT-CT, which was not anticipated in the design, and secondly due to the small number of stage III NSCLC patients with a peripheral tumor that was accessible to SBRT. Nevertheless, the combination of RT-CT and SBRT appeared to be feasible and safe.

Diffuse pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare pre-invasive disease whose pathophysiology remains unclear. We aimed to assess long-term evolution in imaging of DIPNECH, in order to propose follow-up recommendations. Patients with histologically confirmed DIPNECH from four centers, evaluated between 2001 and 2020, were enrolled if they had at least two available chest computed tomography (CT) exams performed at least 24 months apart. CT exams were analyzed for the presence and the evolution of DIPNECH-related CT findings. Twenty-seven patients, mostly of female gender (n = 25/27, 93%) were included. Longitudinal follow-up over a median 63-month duration (IQR: 31–80 months) demonstrated an increase in the size of lung nodules in 19 patients (19/27, 70%) and the occurrence of metastatic spread in three patients (3/27, 11%). The metastatic spread was limited to mediastinal lymph nodes in one patient, whereas the other two patients had both lymph node and distant metastases. The mean time interval between baseline CT scan and metastatic spread was 70 months (14, 74 and 123 months). Therefore, long-term annual imaging follow-up of DIPNECH might be appropriate to encompass the heterogeneous longitudinal behavior of this disease.

Despite advances, malignant pleural mesothelioma (MPM) remains a challenging disease in terms of diagnosis, treatment, and overall management. Herein, we analyzed, in a large-scale single-center cohort, the characteristics and perioperative course of patients undergoing surgical diagnosis of MPM. We identified a total of 514 consecutive patients, 71.4% male and 28.6% female, with mean age 71.3 +/− 13.6 years. Most exhibited pleural, respiratory, or general symptoms and American Society of Anesthesiologists (ASA) score was ≥3 in 68.3% of cases. Thoracoscopy was the most frequent approach (92.0%) and short open thoracotomy was performed in the remaining patients. Pleurodesis was simultaneously performed in 74.3% of cases. Diagnostic failure led to redo surgery in 3.7% of patients. Non-epithelioid histology was found in 19.5% of MPMs and was significantly more frequent in right-sided MPM (p = 0.04), and in patients without history of cancer (p = 0.03), or pleural nodules at thoracoscopy (p = 0.01). Minor only or major complications occurred in respectively 7.8% and 3.6% of cases. They were more frequent in patients ≥ 70 years (p = 0.05) and Performance Status > 2 (p = 0.05). The mean hospital stay was 7.5 days. The 30-day and 90-day early mortality rates were 2.3% and 6.4%, respectively. Surgical diagnosis of MPM is a reliable procedure but is associated with significant morbidity and hospital-stay duration.

Although olfactory disorders (OD) are among the most significant symptoms of COVID-19, recovery time from COVID-19-related OD and their consequences on the quality of life remain poorly documented. We investigated the characteristics and behavioral consequences of COVID-19-related OD using a large-scale study involving 3111 French respondents (78% women) to an online questionnaire over a period of 9 months covering different epidemic waves (from 8 April 2020 to 13 January 2021). In the patients who subjectively recovered from COVID-19-related OD (N = 609), recovery occurred on average after 16 days and most of the time within 1 month (“normal” recovery range); 49 subjectively recovered in 1–2.5 months, and several cases took up to 6.5 months. Among the patients with ongoing OD (N = 2502), 974 were outside the “normal” recovery range (persistent OD) and reported OD for 1–10 months. Developing a persistent OD was more likely with increasing age and in women and was more often associated with parosmia and phantosmia. The deleterious impact of COVID-19-related OD on the quality of life was significantly aggravated by OD duration and was more pronounced in women. Because persistent OD is not infrequent after COVID-19, has deleterious consequences on the quality of life, and receives few solutions from the health practitioners, it would be beneficial to implement screening and treatment programs to minimize the long-term behavioral consequences of COVID-19-related OD.

Introduction Immune checkpoint inhibitors (ICIs) have become part of cancer treatments. Their main side effects are immune-related adverse events (irAEs). So far, there has been no recommendation regarding routine vaccinations during ICIs treatment. Clinicians are aware of the risk of irAEs increases in this specific situation. The aim of this review of literature is to summarize the main studies about vaccination and ICIs interactions. Methods A systematic assessment of literature articles was performed by searching in PubMed (MEDLINE), and major oncology meeting following PRISMA guidelines. Results This review highlights the lack of literature. Indeed, most of the studies published were about influenza vaccination. Vaccination for patients under ICIs causes a humoral response and seems to be associated with an increase rate of seroconversion. Interestingly vaccination may provoke irAEs in ICIs-treated patients. So far, inactivated vaccines have not been contraindicated during ICI treatment. Conclusion Larger prospective studies are needed in order to define a consensus on the use of vaccines under immunotherapy.

Background To assess the ability of procalcitonin (PCT) to distinguish between bacterial and nonbacterial causes of patients with severe acute exacerbation of COPD (AECOPD) admitted to the ICU, we conducted a retrospective analysis of two prospective studies including 375 patients with severe AECOPD with suspected lower respiratory tract infections. PCT levels were sequentially assessed at the time of inclusion, 6 h after and at day 1, using a sensitive immunoassay. The patients were classified according to the presence of a documented bacterial infection (including bacterial and viral coinfection) (BAC + group), or the absence of a documented bacterial infection (i.e., a documented viral infection alone or absence of a documented pathogen) (BAC- group). The accuracy of PCT levels in predicting bacterial infection (BAC + group) vs no bacterial infection (BAC- group) at different time points was evaluated by receiver operating characteristic (ROC) analysis. Results Regarding the entire cohort (n = 375), at any time, the PCT levels significantly differed between groups (Kruskal–Wallis test, p n = 94) than in patients without documented pathogens (n = 218) (p n = 63). For example, the median PCT-H0 levels were 0.64 ng/ml [0.22–0.87] in the bacterial group vs 0.24 ng/ml [0.15–0.37] in the viral group and 0.16 ng/mL [0.11–0.22] in the group without documented pathogens. With a c-index of 0.64 (95% CI; 0.58–0.71) at H0, 0.64 [95% CI 0.57–0.70] at H6 and 0.63 (95% CI; 0.56–0.69) at H24, PCT had a low accuracy for predicting bacterial infection (BAC + group). Conclusion Despite higher PCT levels in severe AECOPD caused by bacterial infection, PCT had a poor accuracy to distinguish between bacterial and nonbacterial infection. Procalcitonin might not be sufficient as a standalone marker for initiating antibiotic treatment in this setting.

Background: Peritoneal carcinomatosis often results in alterations in intestinal peristalsis and recurrent abdominal pain. Pain management in these patients is often unsatisfactory. This study aimed to investigate whether endothelin-1 (EDN1) was involved in pain mediation in peritoneal carcinomatosis, and thus whether the EDN1 pathway could be a new therapeutic target for peritoneal carcinomatosis-associated pain.Methods: EDN1 plasma levels and abdominal pain severity were assessed in patients with abdominal tumors, with or without peritoneal carcinomatosis, and in healthy donors. The effects of EDN1 on the visceromotor response to colorectal distension, and on colonic contractions were then examined in mice, and the mechanism of action of EDN1 was then investigated by measuring the impact of EDN1 exposure on calcium mobilization in cultured neurons. Inhibition studies were also performed to determine if the effects of EDN1 exposure could be reversed by EDN1-specific receptor antagonists.Results: A positive correlation between EDN1 plasma levels and abdominal pain was identified in patients with peritoneal carcinomatosis. EDN1 exposure increased visceral sensitivity and the amplitude of colonic contractions in mice and induced calcium mobilization by direct binding to its receptors on sensory neurons. The effects of EDN1 were inhibited by antagonists of the EDN1 receptors.Conclusions: This preliminary study, using data from patients with peritoneal carcinomatosis combined with data from experiments performed in mice, suggests that EDN1 may play a key role mediating pain in peritoneal carcinomatosis. Our findings suggest that antagonists of the EDN1 receptors might be beneficial in the management of pain in patients with peritoneal carcinomatosis.

Background The coronavirus disease 2019 (COVID-19) outbreak was officially declared in France on March 14, 2020. The objective of this study is to report the incidence and outcome of COVID-19 after surgical resection of non-small cell lung cancer in Paris Public Hospitals during the pandemic. Methods We retrospective analyzed a prospective database including all patients who underwent non-small cell lung cancer resection between March 14, 2020, and May 11, 2020, in the 5 thoracic surgery units of Paris Public Hospitals. The primary endpoint was the occurrence of SARS-CoV-2 infection during the first 30 days after surgery. Results Study group included 115 patients (male 57%, age 64.6 ± 10.7 years, adenocarcinoma 66%, cT1 62%, cN0 82%). During the first month after surgery, 6 patients (5%) were diagnosed with COVID-19. As compared with COVID-negative patients, COVID-positive patients were more likely to be operated on during the first month of the pandemic (100% vs 54%, P = .03) and to be on corticosteroids preoperatively (33% vs 4%, P = .03). Postoperative COVID-19 was associated with an increased rate of readmission (50% vs 5%, P = .004), but no difference in 30-day morbidity (for the study group: grade 2, 24%; grade 3, 7%; grade 4, 1%) or mortality (n = 1 COVID-negative patient, 0.9%). Immediate oncologic outcomes did not differ significantly between groups (R0 resection 99%, nodal upstaging 14%, adjuvant chemotherapy 29%). Conclusions During the COVID-19 pandemic, surgical treatment of non-small cell lung cancer was associated with a rate of postoperative COVID-19 of 5% with a significant impact on readmissions but not on other outcomes studied.

Lung adenocarcinoma is a heterogeneous tumor made of different architectural patterns. These tumors are classified into subtypes according to the predominant pattern in the primary tumor because the predominant pattern is related to overall survival. The prognostic role of these subtypes in stage IV disease is not well known, and most lung adenocarcinomas are diagnosed at the stage of metastatic disease. We aimed to evaluate the prognostic role of histopathological subtypes in lung adenocarcinoma metastases in a retrospective study of 253 patients with clinical, histopathological and molecular data. The presence of the solid subtype was related to overall survival (p = 0.045); the median overall survival was 6.8 months (95 % confidence interval (95 %CI) 4.4-9.1) when present and 11.1 months (95 %CI 8.6-21.3) when absent. Thyroid transcription factor 1 (TTF-1) immunohistochemistry was related to overall survival (p < 0.001); the median overall survival was 11.2 months (95 %CI 8.4-17.7) when positive and 4 months (95 %CI 2.3-5.7) when negative. On multivariate analysis, the presence of the solid subtype (p = 0.0036, hazard ratio (HR) 1.55, 95 %CI 1.03-2.34), TTF-1 positivity (p = 0.044, HR 0.64, 95 %CI 0.42-0.98), age

The use of oral cancer drugs (OAD) has increased over the last two decades. The objective of this study was to measure the impact of a nurse-led telephone follow-up in the therapeutic management of patients treated with an OAD regarding toxicity, medication adherence and quality of life. A randomized, multicenter, controlled trial was conducted. All consecutive over 18-year-old patients, treated in medical oncology, radiotherapy, or hematology departments, receiving OAD for any cancer were invited to participate to the study. A total of 183 patients treated for solid or hematological cancers with an OAD were randomly assigned to receive a nurse-led telephone follow-up or standard care for 24 weeks. Data were collected between 2015 and 2018. Nurse telephone follow-up did not improve the global score toxicity in the intervention group. However, telephone calls directed by trained nurses induced a significant decrease in number of patients with grade 3 adverse events throughout the follow-up [OR 0.45 (IC a 95%) (0.23, 0.9)](P = 0.03). There was no significant difference in quality of life and medication adherence between groups at any follow-up time point. In this first French real-life study, the advice provided by qualified nurses via phone calls improved the management of grade 3 toxicities but failed to demonstrate an improvement of all grades of toxicities. More prospective studies are needed to confirm the impact of telephone calls on the toxicities related to OAD. Clinical trial registration is NCT02459483. Protection committee SUD-ESTI registration is 2015-A00527-42 on 13 April 2015. National Agency for the Safety of Medicines and Health Products registration is 150619-B on the 27 may 2015.

Introduction: Obesity is a major risk factor for chronic disease and cancer development. Therapeutic management of obese patients with cancer is a real challenge for physician because of the alteration of antineoplastic pharmacokinetics parameters in this population. In routine clinical practices, chemotherapy doses in obese patients are arbitrarily capped or adjusted to an ideal weight to minimize excessive toxicities. Material and methods: The main goal of this review is to describe the current state of knowledge concerning the correlation between the adjustment of BSA (capping or ideal weight) and the rates of global toxicities and survival outcomes in obese patients under chemotherapy in different types of cancer. We searched in the Medline database (via PubMed) in order to identify all publications of literature reviews whose subject chemotherapy dosing in obese population. Results: Only a single study was pointing toward increased of global toxicities of full weight dosing. Furthermore, some studies suggests that the practice of limiting doses in overweight and obese patients may negatively influence the quality of care and outcomes in a constantly increasing population. Conclusion: This review highlights the lack of prospective studies focusing on chemotherapy methods of administration in obese patients. At this time, there is no prospective study comparing capping and full weight dose chemotherapy administration in obese patient population.

Summary Background & aims Metastatic non-small cell lung cancer (NSCLC) is the first cause of cancer death worldwide. Increased resting energy expenditure (REE) is frequent among cancer patients and may contribute to cancer cachexia. The aim of this study was to examine the prognostic value of increased REE in metastatic NSCLC patients. Methods This observational study was conducted between June 2012 and November 2017 in the outpatient unit of the oncology department of Cochin hospital, Paris. Consecutive patients with newly diagnosed stage IV NSCLC underwent measurement of REE by indirect calorimetry before treatment initiation. Uni- and multivariate analysis of overall survival (OS, Cox models) included age, sex, smoking habit, histological subtype, performance status, body mass index, weight loss, albumin and CRP levels and the ratio of measured REE to the REE predicted by the Harris Benedict formula (mREE/pREE). Results 144 patients were enrolled: mean age 64 years, 63% male, 90% non-squamous carcinoma, including 17% with ALK/EGFR alteration. In univariate analysis, tobacco consumption (p = 0.007), histo-molecular subtype (p vs ≤ 120%: HR = 2.16, p and ≤120%, respectively. In multivariate analysis, histo-molecular subtype (non-squamous ALK/EGFR mutated vs squamous carcinoma: HR = 0.25, p = 0.006), weight loss (>vs ≤ 5%: HR = 1.98, p = 0.004), albumin (≥vs vs ≤120%: HR = 1.90, p = 0.004) were identified as independent prognostic factors. Conclusions Elevated resting energy expenditure emerges as an independent prognostic factor in metastatic NSCLC.

Sarcopenia is associated with poor outcome in cancer-patients. However, the methods to define sarcopenia are not entirely standardized. We compared several morphometric measurements of sarcopenia and their prognostic value in short-term-outcome prediction after pneumonectomy.Consecutive lung-cancer patients undergoing pneumonectomy from January 2007 to December 2015 and having a pre-operative computed tomography (CT) scan were retrospectively included. Sarcopenia was assessed by the following CT-based parameters measured at the level of the third lumbar vertebra: cross-sectional Total Psoas Area (TPA), cross-sectional Total Muscle Area (TMA), and Total Parietal Muscle Area (TPMA), defined as TMA without TPA. Measures were obtained for entire muscle surface, as well as by excluding fatty infiltration based on CT attenuation. Findings were stratified for gender, and a threshold of 33rd percentile was set to define sarcopenia. Acute Respiratory Failure (ARF), Acute Respiratory Distress Syndrome (ARDS), and 30-day mortality were assessed as parameters of short-term-outcome.Two hundred thirty-four patients with pneumonectomy (right, n = 107; left, n = 127) were analysed. Postoperative mortality rate was 9.0 % (21/234), 17.1 % of patients (40/234) experienced ARF requiring re-intubation, and 10.3 % (24/234) had ARDS. All parameters describing sarcopenia gave significant results; the best discriminating parameter was TMA after excluding fat (p 0.001). While right sided pneumonectomy and sarcopenia were independently associated to the three short-term outcome parameters, Charlson Comorbidity Index only independently predicted ARF.Sarcopenia defined as the sex-related 33rd percentile of fat-excluded TMA at the level of the third lumbar vertebra is the most discriminating parameter to assess short-term-outcome in patients undergoing pneumonectomy.

The widespread use of Nivolumab results in an increasing number of side effects and adverse events. Herein, we evaluated the impact of Nivolumab on crude and normalized pulmonary artery diameter (PAD).We analyzed clinical, morphometric, pathological and radiological data of lung cancer patients treated by Nivolumab in an 18-month period. Blinded radiological evaluation was performed, by three observers measuring axial PAD and Aorta diameter (AoD) in secondarily matched pre- and post-Nivolumab CT-scans. Correlation between ΔPAD and clinicopathological data was investigated.59 patients receiving Nivolumab for treatment of advanced lung carcinoma were identified. Pre-and post-Nivolumab comparison of CT-scan measures revealed that mean PAD was 26.3 ± 2.8 mm versus 28.0 ± 3.0 mm (p 0.001), and mean PAD/AoD ratio was 0.82 ± 0.09 versus 0.87 ± 0.11 (p 0.001), respectively. Median ΔPAD was 0.05 [0.01-0.122] was significantly higher in hypometabolic patients exhibiting low Rest Energy Expenditure (p = 0.03). Patients exhibiting ΔPAD 1% had significantly lower serum albumin level (p = 0.03), and higher nutritional risk (p = 0.02), compared to others. Unlike Nivolumab therapy, there was no increase of PAD after chemotherapy in the same cohort of patients with available scans (n = 45, 25.9 ± 2.9 mm pre-chemotherapy versus 25.7 ± 2.4 mm post-chemotherapy, p = 0.51). Anti-PD-1 treatment was associated with immune-related adverse events in 11 (18.6%) cases including 2 cases of life-threatening acute pulmonary hypertension, both exhibiting post-treatment PAD/AoD ratio 1.Nivolumab is associated to PAD enlargement, a potential marker of pulmonary hypertension, sometimes leading to lethal adverse events. Careful CT-scan and echocardiographic evaluation of PAD should be part of the therapeutic work-up of patients receiving Nivolumab, especially those suffering cancer-associated malnutrition.

Introduction Our objective was to develop and to evaluate a system to measure latency and threshold of pendular motion perception based on a swinging bed. Materials and methods This prospective study included 30 healthy adults (age: 32 ± 12 years). All subjects were tested twice with a 10 min. interval. A second trial was conducted 2 to 15 days after. A rehabilitation swinging bed was connected to an electronic device emitting a beep at the beginning of each oscillation phase with an adjustable time lag. Subjects were blindfolded and auditory cues other than the beep were minimized. The acceleration threshold was measured by letting the bed oscillate freely until a natural break and asking the patient when he did not perceive any motion. The perception latency was determined by asking the patient to indicate whether the beep and the peak of each oscillation were synchronous. The time lag between sound and peak of the head position was swept from -750 to +750 ms by 50 ms increments. Results The mean acceleration threshold was 9.2±4.60 cm/s2. The range width of the synchronous perception interval was estimated as 535±190 ms. The point of subjective synchronicity defined as the center of this interval was -195±106 ms (n = 30). The test-retest evaluation in the same trial showed an acceptable reproducibility for the acceleration threshold and good to excellent for all parameters related to sound-movement latency. Conclusion Swinging bed combined to sound stimulation can provide reproducible information on movement perception in a simple and non-invasive manner with highly reproducible results.

Hypothesizing that pulmonary artery diameter is a marker of subclinical pulmonary hypertension, we assessed its impact on postoperative outcome in patients requiring pneumonectomy. Morphometric, clinical, and laboratory data were retrospectively retrieved from files of 294 consecutive patients treated by pneumonectomy for malignancy (289 NSCLC). Pulmonary artery was measured at bifurcation level on CT scan and normalized by body surface area. Median normalized pulmonary artery diameter (cut-off for analyses) was 14 mm/m2. Postoperatively, 46 patients required re-do intubation and 30 had acute respiratory distress syndrome (ARDS). Multivariate analysis showed that Charlson Comorbidity Index &gt, 5 (p = 0.0009, OR 3.8 [1.76&ndash, 8.22]), right side of pneumonectomy (p = 0.013, OR 2.37 [1.20&ndash, 4.71]), and higher normalized pulmonary artery diameter (p = 0.029, OR 2.16 [1.08&ndash, 4.33]) were independent predictors of re-do intubation, while Charlson Comorbidity Index &gt, 5 (p = 0.018, OR 2.55 [1.17&ndash, 5.59]) and higher normalized pulmonary artery diameter (p = 0.028, OR = 2.52 [1.10&ndash, 5.77]) were independently associated with occurrence of ARDS. Post-operative mortality was 8.5%. Higher normalized pulmonary artery diameter, (p = 0.026, OR 3.39[1.15&ndash, 9.95]), right side of pneumonectomy (p = 0.0074, OR 4.11 [1.46&ndash, 11.56]), and Charlson Comorbidity Index &gt, 5 (p = 0.0011, OR 5.56 [1.99&ndash, 15.54]) were independent predictors of postoperative death. We conclude that pre-operative normalized pulmonary artery diameter predicts the risk of re-do intubation, ARDS and mortality in patients undergoing pneumonectomy for cancer.

Introduction Aneurysmal subarachnoid hemorrhage (SAH) is a devastating form of stroke, which often causes acute hydrocephalus requiring the insertion of an external ventricular drain (EVD). A major complication of aneurysmal SAH is delayed cerebral ischemia (DCI). As DCI is linked to the presence of blood within the subarachnoid space, it has been hypothesized that removing this blood may decrease the risk of DCI. This could be achieved by injecting a fibrinolytic agent through the EVD, a strategy called intraventricular fibrinolysis (IVF). Here, we propose to conduct a phase III trial to directly evaluate the impact of IVF after aneurysmal SAH. Materials and methods We will perform an open-label randomized controlled trial comparing the standard of care, i.e. EVD alone, to the experimental treatment, i.e. IVF. We plan to include 440 patients to be able to show a 10% increase in the rate of good functional outcomes in the EVD + IVF group compared to the EVD alone group (α = 0.05 and β = 0.8). To obtain such sample, a multicenter trial is required, and to date 17 research sites in France have agreed to participate. Perspective FIVHeMA would be the first phase III trial evaluating the relevance of IVF in aneurysmal SAH. If IVF is shown to be beneficial, then a new therapeutic tool will be available to improve the outcomes of aneurysmal SAH patients.

Objective The main objective was to compare estimated walking perimeter (WP) and actual WP during a free walking test (6-minute walk test [6MWT]) in patients with lumbar spinal stenosis (LSS). The second objective was to describe the correlation between measured gait parameters and functional parameters. Methods This was a single-center prospective study including 38 patients with symptomatic LSS (23 men, 15 women; mean age, 69.3 ± 7.9 years). The intervention was the 6MWT. For the main outcome measure, patients were first asked to verbally estimate their WP. Then, WP was evaluated using a 6MWT at a self-selected speed. In the absence of need to stop, and if a distance of 500 m was not reached, the test was extended to this distance. Specific functional scores (Oswestry Disability Index and Quebec Back Pain Disability Scale) were recorded, and a quality of life questionnaire was completed. Results WP was estimated to be less than 500 m in 21 of 38 patients, but only 7 patients actually stopped walking before reaching 500 m. The median estimate error in these patients was 200 m (interquartile range, 65–250). The shorter the estimated distance was, the greater the estimation error (r = −0.63, P = 0.002). The average walking speed was slow. Functional parameters (Oswestry Disability Index and Quebec Back Pain Disability Scale) were weakly and inversely correlated with real WP (r = −0.44 and r = −0.31, respectively) and moderately inversely correlated with measured walking speed (r = −0.51, P ≤ 0.001 for both). Conclusions Direct measurement of free walking speed should be considered as a valid functional assessment in current practice for patients with LSS instead of estimated WP. To assist therapeutic decision-making, the most relevant type of walking test (duration, distance, velocity) needs to be determined.

Purpose: It is usual for cancer patients to use complementary and alternative medicines (CAMs) and yet the literature evaluating their efficacy in cancer patients is very limited. The objective of the present study was to report on the nature, frequency of use, and patient-reported outcome of CAMs in a single-center study. Methods: All the consecutive patients treated between November 2017 and June 2018 at the Lucien Neuwirth Cancer Institute (France) were screened. Their reasons for using CAMs and their usage habits were collected. Patients evaluated their benefit. Results: Of the 209 patients screened, 200 patients were included. CAMs ranged from osteopathy, homeopathy, acupuncture, healing touch, magnetism, naturopathy, suction cups, Chinese medicine, reflexology, to hypnosis. CAMs were widely used (n = 166, 83%), the first being osteopathy (n = 99, 49.5%), the second homeopathy (n = 78, 39.0%), and finally acupuncture (n = 76, 38.0%). Whatever the CAM, high satisfaction rates were reported (median satisfaction: 61–81%). CAMs were mainly used to prevent/treat side effects of anticancer treatments (81.2% for healing touch), increase well-being (55.4% for naturopathy), improve the immune system (16.9% for homeopathy), and treat cancer (n = 3, 5.1% for homeopathy). Patients could easily consider using CAMs, as up to 50.8% would have accepted a consultation. Conclusions: The reasons for using CAMs differed among patients. They praised CAMs and kept asking for more information although there is limited evidence about their efficacy in the literature. Thus, prospective randomized controlled trials exploring the safety and efficacy of CAMs in cancer patients are needed.

Introduction Immune-checkpoint inhibitor (ICI) efficacy in patients with NSCLC harboring molecular alterations remains poorly elucidated. This study was undertaken to determine ICI efficacy against BRAF-, HER2-, MET-, and RET-NSCLC in a real-world setting. Methods In this retrospective, multicenter study in ICI-treated BRAF-, HER2-, MET- or RET-NSCLCs, we analyzed clinical characteristics and outcomes: ICI-treatment duration, progression-free survival (PFS), objective response rate, duration of response, and overall survival (OS). Results There were 107 patients with NSCLC (mean age, 65.5 y) included from 21 centers: 37% were never-smokers, 54% were men, and 93% had adenocarcinoma. Among them, 44 had BRAF mutation (V600: 26), 23 had HER2 mutation, 30 had MET mutation, and nine had RET translocation. Programmed cell death ligand 1 (PD-L1) status was known for 70 patients and was greater than or equal to 1% in 34 patients. Before ICI, patients had received a median of one treatment line. Median duration of response, PFS, and OS were 15.4 (95% confidence interval [CI]: 12.6–not reached [NR]) months, 4.7 (95% CI: 2.3–7.4) months, and 16.2 (95% CI: 12.0–24.0) months, respectively, for the entire cohort. The response rates for BRAF-V600, BRAF–non-V600, HER2, MET, and RET-altered NSCLC were 26%, 35%, 27%, 36%, and 38%, respectively. For patients who were PD-L1 negative and those who were PD-L1 positive, PFS was 3.0 (95% CI: 1.2–NR) and 4.3 (95% CI: 2.1–8.5) months, respectively, and OS was 11.7 (95% CI: 4.1–NR) and 35.8 (95% CI: 9.0–35.2) months, respectively. Toxicities were reported in 28 patients (26%), including 11 patients (10%) with a grade greater than or equal to three. Conclusions In this real-world setting, ICI efficacy against patients with BRAF-, HER2-, MET-, or RET-NSCLC seemed close to that observed in unselected patients with NSCLC. Large prospective studies on these subsets of patients are needed.

Objectives To estimate the 6-month prevalence of generalized anxiety disorder (GAD) in primary care patients aged 70 years and above and to describe their clinical profile, including types of worries. Methods/design Participants (N = 1193) came from the Etude sur la Sante des Aines (ESA) services study conducted in Quebec, Canada. An in-person structured interview was used to identify GAD and other anxiety/depressive disorders as well as to identify types of worries. Three groups were created (ie, patients with GAD, patients with another anxiety disorder, and patients without anxiety disorders) and compared on several sociodemographic and clinical characteristics using multinomial logistic regression analyses. Results The 6-month prevalence of GAD was 2.7%. Findings also indicated that the most common types of worries were about health, being a burden for loved ones, and losing autonomy. Compared with respondents without anxiety disorders, older patients with GAD were more likely to be women, be more educated, suffer from depression, use antidepressants, be unsatisfied with their lives, and use health services. In comparison with respondents with another anxiety disorder, those with GAD were 4.5 times more likely to suffer from minor depression. Conclusions GAD has a high prevalence in primary care patients aged 70 years and above. Clinicians working in primary care settings should screen for GAD, since it remains underdiagnosed. In addition, it may be associated with depression and life dissatisfaction. Screening tools for late-life GAD should include worry themes that are specific to aging.

For malignant pleural mesothelioma (MPM), histopathological subtype is one of the most important prognostic factors. Several immunohistochemical stains whose expressions have possible therapeutic implications have been identified in MPM such as BAP1, mesothelin and PD-L1. The aim of our work was to evaluate the clinical significance and prognostic implications of BAP1, mesothelin and PD-L1 expression in 117 patients with a diagnosis of MPM who were diagnosed in our institution between 2002 and 2017. We also correlated this immunohistochemical profile to a recently described nuclear grading and to histopathological subtype. Mesothelin expression, BAP1 loss and PD-L1 expression were associated with histopathological subtype (p 0.0001), BAP1 loss was more frequent in epithelioid subtype whereas PD-L1 expression was more frequent in non-epithelioid subtype. For epithelioid MPM, BAP1 expression was associated with overall survival (p = 0.034), with a longer survival when BAP1 expression is lost. Necrosis and nuclear grading are associated with overall survival (p = 0.0048 and0.0001, respectively), with longer survival when necrosis was absent and for grade I. For non-epithelioid MPM, overall survival was not related to clinical, histopathological or immunohistochemical expression of BAP1, mesothelin or PD-L1. In multivariate analysis, grade I for nuclear grading was an independent prognostic factor associated with overall survival (p 0.0001). In epithelioid and non-epithelioid MPM, we analysed overall survival in subgroups with combined mesothelin, BAP1 and PD-L1 expression. In epithelioid MPM, BAP1 retained/mesothelin negativity/PD-L1 1%, and BAP1 retained/mesothelin positivity/PD-L1 1% profiles, are associated with shorter overall survival. In non-epithelioid MPM, BAP1 loss/mesothelin negativity/PD-L1 1% is associated with shorter overall survival. Our work confirms that nuclear grading in epithelioid MPM is a strong and independent prognosis factor. Moreover, this study on several promising immunohistochemical stains whose expressions have possible therapeutic implications identifies subgroups with a poor prognosis.

Resume Introduction Le mesotheliome pleural malin (MPM) est une tumeur rare, tres agressive, dont l’incidence est croissante. L’amiante en est le principal agent causal. Etat des connaissances Les connaissances sur le MPM ont evolue. La thoracoscopie est l’examen cle du diagnostic. Elle permet de realiser des biopsies pleurales, d’evaluer l’etendue de la maladie et de soulager la dyspnee. Le diagnostic anatomopathologique est egalement mieux codifie avec l’immunohistochimie et la relecture des lames par le groupe Mesopath. Les traitements chirurgicaux a visee curatrice sont la pleurectomie-decortication et la pleuro-pneumonectomie elargie, en association avec chimio et/ou radiotherapie. Ces traitements lourds n’entrainent d’amelioration de survie que chez des patients tres selectionnes. Les autres patients sont pris en charge de facon palliative ou les enjeux sont les douleurs et la dyspnee. Perspectives Le traitement chirurgical radical n’est propose que dans des essais therapeutiques ou dans les traitements multimodaux. Sa place n’est pas etablie de facon formelle. De nouvelles therapies seules ou associees au traitement chirurgical sont a l’etude. Conclusions Dans l’attente d’avancees therapeutiques, la prise en charge chirurgicale du MPM se fait au sein d’equipes specialisees ou le benefice de survie et de qualite de vie est discute au cas par cas.

Background Supportive care in cancer (SCC) have been recommended to be integrated in the management of patients with lung cancer all along the course of the disease. We took advantage of a pilot program of early implementation of optimized SCC, to report the feasibility such program in patients with advanced lung cancer, and correlate patient characteristics and outcomes with the actual use of optimized SCC. Methods This study is a retrospective analysis of all consecutive patients with lung cancer treated at our center between 2012 and 2016. Optimized SCC included the intervention of a nurse for the home-hospital network coordination, as well as socio-aesthetics, psychomotricity, art-therapy, adapted physical activity, and also establishment of at-home hospitalization. Results 309 patients were included. Median overall survival was 11.2 months. Unplanned hospitalizations occurred for 276 (89%) patients. The median duration of hospital stay was 19 days. Unplanned hospitalizations more frequently occurred within the first 3 months after the diagnosis of advanced cancer, and in the last 3 months before death. A short – less than 3 months – delay between diagnosis and unplanned hospitalization was associated with poor outcome. 272 (88%) patients received optimized SCC, within a median delay of 8 weeks after diagnosis. Intervention of the nurse for in- and out-patient network coordination was done for 143 (46%) patients, and at-home hospitalization was organized for 78 (25%) patients. The outcome of patients who received optimized SCC was numerically, but not significantly better (median overall survival of 11.8 vs. 6.9 months, p = 0.270). Conclusion Our study provides landmark data to support an early integration of optimized SCC for patients with advanced lung cancer, that includes multimodal supportive care interventions along the course of the disease. This highlights the role of multidisciplinary teams to optimize the management of patients with advanced lung cancer.

Autism Spectrum Disorders (ASDs) are characterized by atypical sensory functioning in the visual, tactile, and auditory systems. Although less explored, olfactory changes have been reported in ASD patients. To explore these changes on a neural level, 18 adults with ASD and 18 healthy neurotypical controls were examined in a 2-phase study. Participants were first tested for odor threshold and odor identification. Then, (i) structural magnetic resonance (MR) images of the olfactory bulb were acquired, and (ii) a functional MR imaging olfaction study was conducted. ASD patients exhibited decreased function for odor thresholds and odor identification; this was accompanied by a relatively decreased activation in the piriform cortex. In conclusion, these findings suggest, that the known alterations in olfaction in ASD are rooted in the primary olfactory cortex.

Max-Adrien Garcia,1 Julie Kalecinski,1 Mathieu Oriol,1,2 Armand Bonne,1 Mohamed Lofti,1 Sophie Espenel,3 Fabien Tinquaut,1 Pierre Fournel,4 Olivier Collard,4 Cécile Vassal,4 Romain Rivoirard,4 Véronique Regnier,1,5 Franck Chauvin,1,2,5 Aurélie Bourmaud1,5 1Hygee Center, Lucien Neuwirth Cancer Institut, INSERM – CIC-EC, CIC 1408, Saint Priest en Jarez, France; 2Jean Monnet University, Saint Etienne, France; 3Radiotherapy Department, Lucien Neuwirth Cancer Institut, Saint Priest en Jarez, France; 4Medical Oncology Department, Lucien Neuwirth Cancer Institut, Saint Priest en Jarez, France; 5Quality Safety Performance in Health (HESPER) EA7425, Lyon 1 University, Lyon, France Introduction: The announcement of cancer coupled with initiation of its treatment impacts patients’ psychological and physical states as well as their lifestyles. The objective of this study was to identify and confirm the needs of patients starting off on anticancer chemotherapy treatment. Methods: This study was based on a qualitative–quantitative mixed method. In 2009, a qualitative study was conducted at the Lucien Neuwirth Cancer Institut for cancer patients undergoing intravenous chemotherapy for the first time. Exploratory and semi-directed interviews were carried out by a sociologist. In 2014, a questionnaire was hetero-administered to 100 patients starting off on chemotherapy. Results: Forty patients were interviewed in 2009. Ninety-seven patients answered the questionnaire in 2014. Food was a theme that was identified by a majority of patients in 2009 (13/40) and confirmed in 2014: 63% needed help in identifying favorable food and 67% in identifying those that had to be avoided. The other needs identified were those linked to better understanding of the treatment, of how it may affect the couple, its side effects, hygiene and beauty, and knowledge about other treatments. These needs were confirmed in 2014. New needs were elicited in 2014: activities and leisure (33%), psychological needs (32.6%), and family relations (29.9%). Conclusion: This study enabled us to identify, confirm, and enrich our knowledge of the needs of cancer patients starting off on intravenous chemotherapy. These results led to the modification of an existing patient education program for these patients, in order to fulfill their needs in an updated and tailored manner. Keywords: assessment of needs, patients’ needs, cancer, patient education, mixed qualitative–quantitative method, psychosocial needs

The need to accurately identify cancer outpatients at high risk of thrombotic complications is still unmet. In a prospective, multicenter cohort study (ONCOlogie et Chambres ImPlantables [ONCOCIP]), consecutive adult patients with a solid tumor and implanted port underwent 12-month follow-up. Our primary objective was to identify risk factors for (1) catheter-related thrombosis, defined as ipsilateral symptomatic upper-limb deep-vein thrombosis with or without pulmonary embolism, and (2) venous thromboembolism other than catheter-related, defined as any symptomatic superficial- or deep-vein thrombosis (other than catheter-related) or pulmonary embolism, and incidental pulmonary embolism. All events were objectively confirmed and centrally adjudicated. Rate assessments integrated competing risk of death. Overall, 3032 patients were included (median age: 63 years; women: 58%). The most frequent cancer locations were breast (33.7%), lung (18.5%), and colorectal (15.6%), cancer being metastatic in 43.2% of patients. Most patients (97.1%) received chemotherapy. By 12 months, 48 (1.6%) patients had been lost to follow-up and 656 (24.6%) had died; 3.8% (n = 111) of patients had experienced catheter-related thrombosis, and 9.6% (n = 276) venous thromboembolism other than catheter-related. By multivariate analysis, use of cephalic vein for catheter insertion predicted catheter-related thrombosis, whereas ongoing antiplatelet therapy was protective; risk factors for venous thromboembolism other than catheter-related were advanced age, previous venous thromboembolism, cancer site, and low hemoglobin level or increased leukocyte count before chemotherapy. In conclusion, this large prospective cohort study showed a high rate of venous thromboembolism in patients with a solid tumor and implanted port. Risk factors for catheter-related thrombosis differed from those for venous thromboembolism not catheter-related. This trial was registered at www.clinicaltrials.gov as #NCT02025894.

Septic shock is the primary cause of death in intensive care units, with about 20% of patients dying in the first 3 days. To design future trials focused on early mortality, we require knowledge of early indicators that can detect patients at high risk of early death from refractory septic shock.The aim of this study was to assess whether the cumulative dose of vasopressors (CDV), calculated as the cumulative dose of epinephrine + norepinephrine, is a predictor of early death (within 72 hours) attributable to refractory septic shock (EDASS). This substudy of the EPISS trial was based on 370 patients admitted to a French ICU for septic shock between 2009 and 2011. The area under the receiving operating characteristic (ROC) curve was calculated for the CDV at 6, 12, 24, 36, and 48 hours after vasopressor initiation, and a strategy to predict the risk of EDASS was built based on selected times and thresholds.Among the 370 patients included, 51 (14%) died within the first 72 hours with 40 (11%) EDASS. A strategy in two steps (CDV ≥ 800 μg/kg at 6 hours and/or CDV ≥ 2600 μg/kg at 24 hours) was able to predict EDASS with sensitivity of 45%, specificity 97%, positive predictive value 78% and negative predictive value 94%. Overall, our results confirm that early death directly attributable to septic shock could be effectively predicted by the CDV in the first hours of treatment. These results will help to select patients eligible for innovative therapies aimed at improving early mortality in septic shock.

Thoracic drainage surgery has undergone significant changes over the past ten years. The “dogma” of systematic drainage by means of two tubes was initially called into question, except in special circumstances, such as in case of a significant risk of postoperative bleeding and major air sealing (1).