Assessment of Mendelian and risk-factor genes in Alzheimer disease: A prospective nationwide clinical utility study and recommendations for genetic screening.

PURPOSE: To assess the likely pathogenic/pathogenic (LP/P) variants rates in Mendelian dementia genes and the moderate-to-strong risk factors rates in patients with Alzheimer disease (AD). METHODS: We included 700 patients in a prospective study and performed exome sequencing. A panel of 28 Mendelian and 6 risk-factor genes was interpreted and returned to patients. We built a framework for risk variant interpretation and risk gradation and assessed the detection rates among early-onset AD (EOAD, age of onset (AOO) ≤65 years, n = 608) depending on AOO and pedigree structure and late-onset AD (66 < AOO < 75, n = 92). RESULTS: Twenty-one patients carried a LP/P variant in a Mendelian gene (all with EOAD, 3.4%), 20 of 21 affected APP, PSEN1, or PSEN2. LP/P variant detection rates in EOAD ranged from 1.7% to 11.6% based on AOO and pedigree structure. Risk factors were found in 69.5% of the remaining 679 patients, including 83 (12.2%) being heterozygotes for rare risk variants, in decreasing order of frequency, in TREM2, ABCA7, ATP8B4, SORL1, and ABCA1, including 5 heterozygotes for multiple rare risk variants, suggesting non-monogenic inheritance, even in some autosomal-dominant-like pedigrees. CONCLUSION: We suggest that genetic screening should be proposed to all EOAD patients and should no longer be prioritized based on pedigree structure.

Anatomic patterns of anastomotic leaks after Ivor Lewis esophagectomy for cancer: Impact on management and outcomes.

BACKGROUND: Anastomotic leakage presentation after Ivor Lewis esophagectomy may vary on imaging. Such variations may influence anastomotic leakage management and outcomes. METHODS: All consecutive patients who underwent Ivor Lewis esophagectomy for cancer between 2012 and 2019 in 2 referral centers were included. Anatomical patterns of anastomotic leakage were defined on imaging as follows: eso-mediastinal anastomotic leakage was a leak contained in the posterior mediastinum, eso-pleural anastomotic leakage was a leak involving the pleural cavity, and eso-bronchial anastomotic leakage was a leak communicating with the tracheobronchial tract. According to the Esophageal Complications Consensus Group definition, management and 90-day mortality were evaluated according to these patterns. RESULTS: Among 731 patients, 111 (15%) developed anastomotic leakage consisting of eso-mediastinal anastomotic leakage (n = 87, 79%), eso-pleural anastomotic leakage (n = 16, 14%) and eso-bronchial anastomotic leakage (n = 8, 7%). There was no difference among these groups regarding preoperative characteristics or time to anastomotic leakage diagnosis. There was a significant difference in initial management according to anastomotic leakage anatomic patterns (P = .001). More than half of patients who experienced eso-mediastinal anastomotic leakage (n = 46, 53%) were initially treated conservatively without requiring intervention (Esophageal Complications Consensus Group type I), whereas most patients with eso-pleural anastomotic leakage (n = 14, 87.5%) and all with eso-bronchial anastomotic leakage (n = 8, 100%) initially required interventional or surgical treatment (Esophageal Complications Consensus Group type II-III). Anastomotic leakage anatomic patterns had a statistically significant impact on 90-day mortality, intensive care unit stay, and total hospital stay (P < .001). CONCLUSION: Anastomotic leakage anatomic patterns after Ivor Lewis esophagectomy influence outcomes. Further studies are warranted to validate it in a prospective setting. Anastomotic leakage anatomic patterns may help in guiding anastomotic leakage management.

In-orbit demonstration of a re-trainable machine learning payload for processing optical imagery.

Cognitive cloud computing in space (3CS) describes a new frontier of space innovation powered by Artificial Intelligence, enabling an explosion of new applications in observing our planet and enabling deep space exploration. In this framework, machine learning (ML) payloads-isolated software capable of extracting high level information from onboard sensors-are key to accomplish this vision. In this work we demonstrate, in a satellite deployed in orbit, a ML payload called 'WorldFloods' that is able to send compressed flood maps from sensed images. In particular, we perform a set of experiments to: (1) compare different segmentation models on different processing variables critical for onboard deployment, (2) show that we can produce, onboard, vectorised polygons delineating the detected flood water from a full Sentinel-2 tile, (3) retrain the model with few images of the onboard sensor downlinked to Earth and (4) demonstrate that this new model can be uplinked to the satellite and run on new images acquired by its camera. Overall our work demonstrates that ML-based models deployed in orbit can be updated if new information is available, paving the way for agile integration of onboard and onground processing and "on the fly" continuous learning.

Impact of the Covid-19 pandemic context on the microbiological epidemiology and management of flexor sheath phlegmons.

INTRODUCTION: The COVID-19 pandemic in France has recently modified the patients' lifestyles, as well as methods of medical and surgical management. This could explain subsequent changes to the microbiological spectrum, the severity, as well as the scalability of phlegmons of the flexor tendon sheath. The objective of this study was to construct an epidemiological and bacteriological inventory of these hand infections, and to compare the clinical and microbiological data, before and after the COVID-19 pandemic. HYPOTHESIS: The hypothesis of this work was that the phlegmons of the flexor tendon sheath presented specific microbiological characteristics in the tropical environment of our University Hospital Center, and that these characteristics could have changed with the recent introduction of hydro-alcoholic solution (HAS) associated to the COVID-19 pandemic. MATERIAL AND METHODS: The preoperative epidemiological data of our patients were collected between January 2016 and December 2020. The stage of severity, according to the classification of Michon, the use of hydro-alcoholic solution, as well as the early clinical evolution were collected. The cohort was then divided into two groups in order to compare the microbiological profiles, the management and the clinical evolution of patients in the pre-COVID period with those in the post-COVID period. RESULTS: A total of 199 patients were included, 154 patients in the pre-COVID period and 26 in the post-COVID period. We found a majority of MSSA (58.3%, N=105) and negative samples comprised 18.9% (N=34). No statistically significant difference was found between the two groups regarding the bacteriological results. The clinical course was judged to be favorable in 93.5% of cases in the pre-COVID group compared to 80.8% in the post-COVID group (p=0.046). The use of HAS (p<0.0001), as well as the initial stage of severity according to Michon, were significantly higher in group 2 (p=0.04). DISCUSSION: The COVID-19 pandemic has not shown any change in the microbiological spectrum, despite the now daily use of HAS in everyday life. The postoperative clinical evolution was significantly less favorable after the onset of COVID and could be explained by an increase in cases with a more advanced initial stage of severity. LEVEL OF EVIDENCE: IV, Observational epidemiological study.

Could 18-FDG PET-CT Radiomic Features Predict the Locoregional Progression-Free Survival in Inoperable or Unresectable Oesophageal Cancer?

Background: We evaluated the value of pre-treatment positron-emission tomography−computed tomography (PET-CT)-based radiomic features in predicting the locoregional progression-free survival (LR-PFS) of patients with inoperable or unresectable oesophageal cancer. Material and Methods: Forty-six patients were included and 230 radiomic parameters were extracted. After a principal component analysis (PCA), we identified the more robust radiomic parameters, and we used them to develop a heatmap. Finally, we correlated these radiomic features with LR-PFS. Results: The median follow-up time was 17 months. The two-year LR-PFS and PFS rates were 35.9% (95% CI: 18.9−53.3) and 21.6% (95%CI: 10.0−36.2), respectively. After the correlation analysis, we identified 55 radiomic parameters that were included in the heatmap. According to the results of the hierarchical clustering, we identified two groups of patients presenting statistically different median LR-PFSs (22.8 months vs. 9.9 months; HR = 2.64; 95% CI 0.97−7.15; p = 0.0573). We also identified two radiomic features ("F_rlm_rl_entr_per" and "F_rlm_2_5D_rl_entr") significantly associated with LR-PFS. Patients expressing a "F_rlm_2_5D_rl_entr" of <3.3 had a better median LR- PFS (29.4 months vs. 8.2 months; p = 0.0343). Patients presenting a "F_rlm_rl_entr_per" of <4.7 had a better median LR-PFS (50.4 months vs. 9.9 months; p = 0.0132). Conclusion: We identified two radiomic signatures associated with a lower risk of locoregional relapse after CRT.

Clostridium haemolyticum Infection: A Cause of Hemolytic Anemia in a Patient with Bone Marrow Necrosis.

Clostridium haemolyticum is a sporulating Gram-positive anaerobic rod that is considered to be one of the most fastidious and oxygen-sensitive anaerobes. It is a well-known animal pathogen and the cause of bacillary hemoglobinuria primarily in cattle. To date, human infections caused by C. haemolyticum have been reported in three patients with malignant underlying diseases. We present herein the case of a 30-year-old obese woman with no significant past medical history who developed bacteremia caused by C. haemolyticum with massive intravascular hemolysis associated with bone marrow necrosis and acute renal failure. Because of subculture failure, the diagnosis was made on the basis of 16S rDNA sequencing and next-generation sequencing. The patient, who had been afebrile for 20 days after a 17-day-course of antibiotics, experienced a second bacteremic episode caused by C. haemolyticum. After having been successfully treated for 42 days with clindamycin and amoxicillin-clavulanic acid, the patient developed acute myeloid leukemia as a result of bone marrow regeneration. Although uncommon in humans, infections caused by C. haemolyticum are severe and should be considered in a febrile patient who has severe hemolytic anemia. This case also highlights the importance of using molecular techniques for the identification of this fastidious anaerobic organism.

Is subtalar arthroereisis a good procedure in adult-acquired flatfoot? A systematic review of the literature.

INTRODUCTION: The aim of the present systematic literature review was to determine results and complications in subtalar arthroereisis for stage-2 adult-acquired flatfoot. METHOD: A search of the PubMed, Medline, CINAHL, Cochrane and Embase databases used MeSH terms "arthroereisis" AND "flatfoot" OR "adult-acquired flatfoot" OR "pes planovalgus" OR "pes planus". Two of the authors analyzed 125 articles. After reading titles and Abstracts, 105 articles were read in full text and their references were analyzed. Finally, 12 articles were selected and divided into 2 groups: isolated and associated arthroereisis. RESULTS: Improvement in functional scores was greater in associated arthroereisis. Whether isolated or associated, arthroereisis achieved radiologic correction. However, the rate of complications was high, mainly concerning tarsal sinus pain. CONCLUSION: Subtalar arthroereisis for stage-2 adult-acquired flatfoot is rarely performed in isolation. When it is associated to other procedures, good radiologic and clinical results can be expected. LEVEL OF EVIDENCE: IV.

[Oesophagus polyps: Giant fibrovascular polyp of the oesophagus disappears!] / Polypes œsophagiens : le polype géant fibrovasculaire de l'œsophage n'existe plus !

The giant fibrovascular polyp of the esophagus is a rare, benign and typical entity described in 1957. This lesion is easily identifiable in its macroscopic and microscopic aspects. However, recent studies question the existence of the giant fibrovascular polyp of the esophagus. The demonstration of an amplification of the MDM2 gene poses the diagnosis of well-differentiated liposarcoma. We describe here a case of an esophagus polyp in a 67-year-old man. The diagnosis of giant fibrovascular polyp of the esophagus was initially retained. Secondly, the immunohistochemical and fluorescence in situ hybridization techniques showed amplification of the MDM2 gene and reclassified the lesion to a well-differentiated liposarcoma. The search for an undifferentiated contingent is essential to not ignore a dedifferentiated liposarcoma, which is a high-grade sarcoma with a poorer prognosis.

Is non-operative treatment still relevant for Garden Type I fractures in elderly patients? The femoral neck impaction angle as a new CT parameter for determining the indications of non-operative treatment.

BACKGROUND: The indications of non-operative treatment of undisplaced femoral neck fractures are controversial. The objective of this study was to assess whether two computed tomography (CT) parameters, the femoral neck impaction angle (IA) and the femoral neck posterior tilt angle (PTA), were effective in predicting the risk of secondary displacement after non-operative treatment of Garden I femoral neck fractures in patients aged 65 years or over. HYPOTHESIS: The working hypotheses were that the IA in the coronal plane and PTA in the axial plane predicted secondary displacement after non-operative treatment of Garden I femoral neck fractures, could be reproducibly and reliably measured on CT scans, and could serve to identify Garden I fractures at risk for secondary displacement after non-operative treatment. METHODS: Forty-nine patients aged 65 years or over with Garden I fractures treated non-operatively were included in a prospective single-centre study. CT images were used to measure the IA as the position of the fracture line relative to the femoral head in the coronal plane and the PTA as the position of the femoral head centre relative to the femoral neck axis in the axial plane. RESULTS: After non-operative treatment, secondary displacement occurred in 22 (45%) patients. The PTA was not significantly different between the groups with vs. without secondary displacement (p=0.62). IA values≤135° were significantly associated with secondary displacement (odds ratio, 11.73; 95% confidence interval [95%CI], 3.04-45.28; p=0.004). An IA≤135° was 72.73% sensitive and 81.48% specific for predicting secondary displacement. IA measurement was reproducible, with intra-class and inter-class Cohen's kappa values of 0.94 (95%CI, 0.90-0.97) and 0.9011 (95%CI, 0.83-0.94), respectively. DISCUSSION: The IA measured on CT images may hold promise for identifying Garden I hip fractures at high risk for secondary displacement after non-operative treatment. IA measurement is reproducible and reliable and may help to determine the indications of non-operative treatment. LEVEL OF EVIDENCE: II, prospective cohort study.

Biceps Brachii Muscle Synergy and Target Reaching in a Virtual Environment.

A muscular synergy is a theory suggesting that the central nervous system uses few commands to activate a group of muscles to produce a given movement. Here, we investigate how a muscle synergy extracted from a single muscle can be at the origin of different signals which could facilitate the control of modern upper limb myoelectric prostheses with many degrees of freedom. Five pairs of surface electrodes were positioned across the biceps of 12 normal subjects and electromyographic (EMG) signals were collected while their upper limbs were in eight different static postures. Those signals were used to move, within a virtual cube, a small red sphere toward different targets. With three muscular synergies extracted from the five EMG signals, a classifier was trained to identify which synergy pattern was associated with a given static posture. Later, when a posture was recognized, the result was a displacement of a red sphere toward a corner of a virtual cube presented on a computer screen. The axes of the cube were assigned to the shoulder, elbow and wrist joint while each of its the corners was associated with a static posture. The goal for subjects was to reach, one at a time, the four targets positioned at different locations and heights in the virtual cube with different sequences of postures. The results of 12 normal subjects indicate that with the muscular synergies of the biceps brachii, it was possible, but not easy for an untrained person, to reach a target on each trial. Thus, as a proof of concept, we show that features of the biceps muscular synergy have the potential to facilitate the control of upper limb myoelectric prostheses. To our knowledge, this has never been shown before.

Static hand posture classification based on the biceps brachii muscle synergy features.

With modern upper limb myoelectric prostheses, many movements can be produced when many control signals are available. Some of them could originate from the multifunctional biceps brachii which appears to be composed of up to six individually innervated compartments. Given its compartmental nature, this muscle behaves as if composed of many individual muscles acting in synergy to achieve a given motor task. Through an appropriate synergy model, its EMG signals could thus be used to produce some of the many control signals required with modern upper limb myoelectric prostheses. Exploring that possibility, muscular synergy which is usually applied to a group of different muscles, was tested on the biceps brachii only. A non-negative matrix factorization method was applied on pre-recorded data consisting of 8 surface electromyographic signals collected across the biceps of 10 normal subjects who, in Seat or Stand posture, held their hand in 3 different postures. We found that muscular synergies can be extracted from the biceps brachii. With a learning process and a classifier, it was also possible, between a pair of static hand postures, to identify which one was used when a given record was made. The mean score of correctly detected hand posture was >80% for our subjects.

Mid-infrared nonlinear absorption in As2S3 chalcogenide glass.

We report mid-infrared (MIR) nonlinear absorption in As2S3 glasses which results from two-photon excitation of valence electron to the Urbach extension followed by strong linear absorption of excited states. The measured MIR nonlinear absorption can be 3 to 4 orders of magnitude stronger than the two-photon absorption in the near-infrared for similar laser intensities and does not result from contaminants, but it is intrinsic to As2S3 glasses. As2S3 fibers are widely used to generate supercontinuum by pumping them with high peak power laser pulses. For a 100 kilowatt peak power MIR soliton propagating in single mode As2S3 fiber, the nonlinear absorption can be of similar magnitude than the fiber background loss. Finally, for laser peak power around 1 MW, the MIR nonlinear absorption can be ~2 orders of magnitude larger than the fiber background loss in single mode As2S3 fiber.

Docetaxel, Cisplatin, and 5-Fluorouracil as perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma.

Docetaxel, cisplatin, and 5-fluorouracil (DCF) significantly improved overall survival in metastatic gastroesophageal adenocarcinoma (GEA). The aim of this study was to assess efficacy of DCF regimen as perioperative chemotherapy compared with surgery alone in patients with resectable GEA. We identified 789 patients who underwent surgery alone and 62 patients who received at least one cycle of DCF regimen consisting of docetaxel (75 mg/m2 on day 1), cisplatin (75 mg/m2 on day 1), and 5-fluorouracil (750 mg/m2 /day on continuous perfusion on days 1 to 5), every 3 weeks. Overall survival was compared using Cox proportional hazards regression model with adjustments for confounding factors provided by two propensity score methods: inverse probability of treatment weighting (IPTW) and matched-pair analysis. In Cox multivariate analysis weighted by IPTW, DCF group was associated with favorable overall survival (OS) compared with the surgery group (HR = 0.59; 95% CI, 0.45-0.78; P = 0.0003). For the matched-pair analysis (comparing 41 patients for each group with the same baseline characteristics), median OS was 22 months and 57 months for the surgery group and DCF group, respectively (log-rank P = 0.0011). In Cox multivariate analysis, DCF group was associated with favorable OS compared with the surgery group (HR = 0.29; 95% IC, 0.14-0.64; P = 0.0019). In the matched-pair population, major complications (Dindo-Clavien grade 3-5) arose in six patients (14.63%) in the DCF group and seven patients (17.07%) in the surgery group (P = 1). Perioperative DCF chemotherapy is superior to surgery alone in terms of OS. A randomized phase III trial should compare DCF to standard perioperative regimens.

Steroids, lidocain and ioxaglic acid modify the viscosity of hyaluronic acid: in vitro study and clinical implications.

BACKGROUND: Viscosupplementaion by intra-articular injection of hyaluronic acid (HA) is a therapeutic modality for treating osteoarthritis of the knee, of the hip and less frequently of other joints. During viscosupplementation, it is usual to inject other drugs, without knowing whether this association may have a deleterious effect thereon. The rheological properties of a viscosupplement are highly dependent on the product [molecular weight × concentration] of HA. Therefore, any reduction of its viscoelastic properties is related either to a decrease of its concentration or/and of its molecular weight. The presence of other molecules can create favorable or unfavorable molecular interactions with HA. The objective of the study was to investigate the effect of products, that are commonly associated with HA (corticosteroids, lidocain, iodinated contrast media), on the rheological behavior of HA, then to try drawing practical conclusions. METHODS: The rheological behavior of both a linear and a cross-linked HA, was studied before and after mixing with different volumes (ratio 1:0.5-1:4) of the following compounds: phosphate buffered saline (PBS, as a control), cortivazol, triamcinolone hexacetonide, lidocain chlorhydrate and meglumine ioxaglate. The flow curve of the different samples was obtained using a measuring method based on a constant shear rate. RESULTS: Whatever the dilution and the added molecule were, viscosity of the cross-linked viscosupplement remained much higher than that of the linear one. Addition of PBS at a ratio 1:1 caused a dramatic decrease (up to 97.5 %) of HA viscosity. Cortivazol and lidocain had a similar effect than PBS on linear HA. Both were much deleterious on cross-linked HA viscosity. Among corticosteroids, triamcinolone decreased much less HA viscosity than cortivazol. The effect of meglumine ioxaglate was dose-dependent. Up to a ratio 1:1 viscosity of the linear HA remained above the dilution effect. On the cross-linked HA, the deleterious effect of the contrast agent was evident as soon as a ratio 1:1 and became very marked at 1:2. CONCLUSION: HA viscosity varies widely in presence of other molecules. These changes are due to both dilution and molecular interactions. This study suggests that addition of other molecules with HA can lead to a major decrease of its viscosity. However, provided to respect a maximum ratio of 1:1, the contrast medium and triamcinolone seem to have no major deleterious effect on the viscosity level, especially on crosslinked HA. The study also suggests a deleterious effect of lidocain on the cross-linked HA. These in vitro data suggest that drugs associations must be avoided when they are not essential. However, clinical trials are needed to determine whether these rheological changes may have a significant impact on the clinical outcome.

Leap Motion Gesture Control With Carestream Software in the Operating Room to Control Imaging: Installation Guide and Discussion.

Nowadays, routine cross-sectional imaging viewing during a surgical procedure requires physical contact with an interface (mouse or touch-sensitive screen). Such contact risks exposure to aseptic conditions and causes loss of time. Devices such as the recently introduced Leap Motion (Leap Motion Society, San Francisco, CA), which enables interaction with the computer without any physical contact, are of wide interest in the field of surgery, but configuration and ergonomics are key challenges for the practitioner, imaging software, and surgical environment. This article aims to suggest an easy configuration of Leap Motion on a PC for optimized use with Carestream Vue PACS v11.3.4 (Carestream Health, Inc, Rochester, NY) using a plug-in (to download at https://drive.google.com/open?id=0B_F4eBeBQc3yNENvTXlnY09qS00&authuser=0) and a video tutorial (https://www.youtube.com/watch?v=yVPTgxg-SIk). Videos of surgical procedure and discussion about innovative gesture control technology and its various configurations are provided in this article.

Reconstruction of the Lateral Ligaments of the Ankle Using a Periosteal Flap in Children and Teenagers: A Midterm Follow-up Survey.

BACKGROUND: The rate of chronic lateral ankle instability has increased in children and teenagers. However, studies concerning its management within this population are rare. Current repair techniques involve use of the peroneus brevis tendon. Herein, we have described and evaluated a method utilizing a regional periosteal flap for reconstructing the lateral ligaments of the ankle. METHODS: We conducted a single-center, retrospective study over a 4-year period. For functional assessment, we used the American Orthopedic Foot and Ankle Society (AOFAS) score as well as Gould's criteria. For radiologic assessment, we calculated the tibiotalar tilt and anterior translation of the talus. RESULTS: A total of 14 children were included in this study. The mean age of patients was 12.7 years old, and the mean follow-up was 3.1 years. The mean AOFAS score evolved from 61 points (before surgery) to 95 points after surgery (P<0.001). The Gould classification revealed 11 excellent, 2 good, 1 average, and no bad outcomes. Further, surgical intervention led to evolution of the tibiotalar tilt from 14 to 4 degrees (P<0.001), whereas the anterior translation of the talus went from 11 to 2 mm (P<0.001). The mean skeletal age was 12.5 years. No case of epiphysiodesis of the lateral malleolus or heterotopic bone was found. It appears that nonanatomic reconstruction involving the peroneus brevis can be avoided in young patients. Because of the frequent impossibility of ligament suturing within this population, we have developed a reconstruction technique involving the use of a regional periosteal flap. Notably, in the case of recurrence, the patients' peroneus brevis tendons remain intact for future procedures. CONCLUSIONS: Repair involving the periosteal flap yields good clinical and radiologic results. Our preliminary findings are encouraging and suggest that this technique should be evaluated in a larger patient population with long-term follow-up. LEVEL OF EVIDENCE IV: Retrospective study.

Multioctave infrared supercontinuum generation in large-core As2S3 fibers.

We report on infrared supercontinuum (SC) generation through laser filamentation and subsequent nonlinear propagation in a step-index As2S3 fiber. The 100 µm core and high-purity As2S3 fiber used exhibit zero-dispersion wavelength around 4.5 µm, a mid-infrared background loss of 0.2 dB/m, and a maximum loss of only 0.55 dB/m at the S-H absorption peak around 4.05 µm. When pumping with ultrashort laser pulses slightly above the S-H absorption band, broadband infrared supercontinua were generated with a 20 dB spectral flatness spanning from 1.5 up to 7 µm. The efficiency and spectral shape of the SC produced by ultrashort pulses in large-core As2S3 fiber are mainly determined by its dispersion, the S-H contaminant absorption, and the mid-infrared nonlinear absorption.

[A letal case of gastro-intestinal basidiobolomycosis]. / Une forme gastro-intestinale de basidiobolomycose d'évolution fatale.

We report here the case of a 55-year-old man from Mali, who presented with abdominal pain. Radiological exploration revealed an ileo-colonic mass surrounding the appendix. A biopsy was taken and on histology, transmural granulomatous inflammation of numerous eosinophils, lymphocytes, plasmocytes and giant cells was seen. Tuberculosis was suspected clinically and an antibiotic treatment was initiated. Two months later, the patient died of septic complications. Basidiobolus ranarum was identified by PCR. Pathogens were retrospectively highlighted on biopsies. These elements were between 10 and 15 µm in diameter, occasionally pseudo-septated, and were surrounded by a thick eosinophilic cuff. The thick eosinophilic cuff was identified as the Splendore-Hoeppli phenomenon. Basidiobolomycosis is a well-known infection in the tropical areas. Basidiobolus sp., fungus of the order Entomophtorales are a known cause of chronic subcutaneous mycosis. Gastro-intestinal basidiobolomycosis is rare and presents considerable diagnostic difficulty. This infection needs to be diagnosed because surgical resection and prolonged antifungal treatment are curable in most cases.

Phase II multicentre study of efficacy and feasibility of dose-intensified preoperative weekly cisplatin, epirubicin, and paclitaxel (PET) in resectable gastroesophageal cancer.

BACKGROUND: Perioperative chemotherapy improves the overall survival of resectable gastroesophageal adenocarcinoma (GEA) patients. However, more than 40 % of the patients are not healthy enough to complete their post-operative chemotherapy, and the progression-free survival rate is lower than 35 % at 5 years. In order to optimise neoadjuvant chemotherapy regimen, a pilot study of weekly dose-intensified cisplatin, epirubicin, and paclitaxel (PET) was conducted. The primary objective was a complete resection (R0) rate. Then, a R0 rate ≤80 % was considered as uninteresting, with an expected R0 rate of 92 %. Secondary objectives were the feasibility, safety, histological response rate (Becker score), and survival (Trial registration: NCT01830270). METHODS: Patients with >T1N0M0 GEA were included. Treatment consisted of eight preoperative cycles of weekly PET regimen at 30/50/80 mg/m² of cisplatin, epirubicin, and paclitaxel, respectively. Primary prophylaxis by granulocyte colony-stimulating factor was administered. Surgery was performed 4-6 weeks following the last cycle of chemotherapy. Using Fleming two-step design with a unilateral alpha type one error of 5 % and a statistical power of 80 %, it would be required to include 68 patients. At planned interim analysis for futility, it was required to observe at least 25 of 29 patients with R0 resection to pursue inclusion. At the second step, it was required to observe at least 61 of 68 patients with R0 resection to conclude for promising activity of the dose-intensified chemotherapy. RESULTS: Between May 2011 and January 2013, 29 patients were enrolled. Median age was 62 years (range 39-83 years), and seven (24 %) patients presented signet-ring cell histology. Twenty-seven (93 %) patients underwent surgery. Pathological complete responses (Becker score 1a) were observed in four patients, and nearly complete responses (Becker score 1b) for additional three patients. A R0 rate was achieved for 24 of 29 (82.7 %; 95 % CI 64-94 %) patients. No Becker score 1a/1b response was observed among patients with signet-ring cell GEA. Twenty-one (72 %) patients completed all eight cycles, and 86 % received seven or more cycles. Sixteen (56 %) patients experienced grade 3-4 neutropenia, and five patients had febrile neutropenia. Among non-haematological toxicities, mucositis and fatigue were the most frequent ones. The median-delivered relative dose intensity (DI) was 80 % for cisplatin, 75 % for epirubicin, and 79 % for paclitaxel. However, only 45 % of the patients received at least 80 % of the planned median DI for all three drugs. CONCLUSIONS: Despite high R0 and pathological response rates, neoadjuvant PET chemotherapy did not meet the primary end-point and failed to show an acceptable relative DI. PET chemotherapy is not recommended in resectable GEA patients.