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Background: The debate surrounding the influence of the open Latarjet procedure on postoperative scapular motions persists, and there is no evidence regarding its effects on periscapular muscle activation. This study aimed to assess the short-term influence of the open Latarjet procedure on scapular kinematics and periscapular muscle activity during arm raising and lowering based on comparisons between patients and healthy athletes., Methods: 22 healthy male athletes and 22 male athletes scheduled for glenohumeral stabilization surgery by the open Latarjet procedure were included. Scapular kinematics, periscapular muscle activities, and shoulder-related quality of life were recorded before surgery and 3 months postoperatively for the Latarjet group. For the healthy group, same assessments were performed 3 months apart. Bilateral differences in both scapular kinematics and periscapular muscle activation ratios and the Western Ontario Shoulder Instability (WOSI) index were defined as dependent variables., Results: Scapular kinematics of the operated shoulder, namely scapular upward/downward rotation, internal/external rotation, and anterior/posterior tilt recorded between 20° and 120° of humerothoracic elevation, showed no alterations 3 months after surgery (P > .05) and did not differ from those observed in healthy athletes (P > .05). Similarly, all periscapular muscle activations were not different within time and between groups (P > .05). The WOSI index of the operated shoulder was significantly improved postoperatively (871.9 ± 443.7 vs. 1346.3 ± 552.3) but remained higher than the WOSI indices of the nonoperated shoulder or those of the healthy group (52.7 ± 75.6)., Conclusions: This study emphasizes the short-term effects of the open Latarjet procedure, demonstrating an improvement in the shoulder-related quality of life 3 months after surgery. Notably, during this period, both kinematics and periscapular muscle activity remained consistent and similar to the patterns observed for healthy athletes., (Copyright © 2024 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Purpose: Genomic profiling is a major component for first-line treatment decisions in patients with non-small cell lung cancer (NSCLC) and the timeliness of biomarker testing is essential to improve time to treatment initiation (TTI) or avoid inappropriate treatment., Patients and Methods: The phase III LIBELULE trial (NCT03721120) included patients with radiological suspicion of advanced lung cancer. They were randomized (1:1), the control arm receiving diagnostic procedures according to each center's practice and the liquid biopsy arm with additional testing performed at the first visit using the InVisionFirst®-Lung assay. Treatment initiation and type were defined according to ESMO guidelines. Primary endpoint was the time from randomization to initiation of appropriate treatment based on informative genomic and pathological results in the intention-to-treat population., Results: 319 patients were enrolled (LB: 161; control: 158). Median age was 68 years, 28.8% were non-smokers, 18.1% had PS≥2 and 56.7% had adenocarcinoma. In LB arm, 81% of patients had circulating tumor DNA findings. The mean TTI was not significantly reduced (LB: 29.0 days (d); control 34d (p=0.26)). Sensitivity analyses showed a shorter TTI in patients from the LB arm who received systemic treatment (LB: 29.1d; control: 38.8d, p=0.01), in patients with advanced non-squamous NSCLC (LB: 29.5d; control: 40.3d, p=0.01), and in patients with first-line targetable alterations (LB: 21d; control 37.4d) (p=0.004). Time to contributory genomic results was significantly reduced (LB: 17.9d; control 25.6d, p<0.001)., Conclusion: Early liquid biopsy testing did not significantly shorten the TTI in unselected patients referred for suspected advanced lung cancer. Nevertheless, it could reduce the TTI in patients eligible for systemic treatment, particularly for those with actionable alterations., (Copyright © 2024. Published by Elsevier Inc.)

Background: Although it is considered a sensitive indicator of shoulder disabilities, the scapulohumeral rhythm has not been investigated after anterior glenohumeral stabilization with open Latarjet procedure. This study aimed to assess the short-term influence of glenohumeral stabilization on scapulohumeral rhythm in patients who underwent open Latarjet procedure compared to asymptomatic individuals., Methods: A group of male patients who underwent anterior glenohumeral stabilization by open Latarjet procedure and a healthy group were enrolled in this study. An electromagnetic device was used to record scapulothoracic and glenohumeral joint kinematics during dynamic arm elevation and depression in the scapular plane before and three months after surgery. Then, the three-dimensional dynamic scapulohumeral rhythm was computed bilaterally. SPM ANOVAs were used for statistical analysis., Findings: Twenty-two participants per group were included. The scapulohumeral rhythm of the two groups increased from 1.88 [mean] ± 0.79 [standard deviation] to 2.83 ± 1.52 during the ascending phase, while a decrease followed by a slight increase in the scapulohumeral rhythm were observed during the descending phase. The scapulohumeral rhythm did not significantly differ between the operated and non-operated sides or before and after surgery. When pooling the sides for each group, no significant differences were observed between the groups., Interpretation: The scapulohumeral rhythm in patients who underwent the Latarjet procedure is not modified three months after surgery and is similar to the scapulohumeral rhythm of asymptomatic individuals. These findings suggest that in addition to restoring glenohumeral stability, the open Latarjet procedure preserves shoulder joint coordination three months postoperatively., Competing Interests: Declaration of competing interest Y Blache, M Degot and I Rogowski declare no conflict of interest. L Neyton is a paid consultant for Wright Medical and Arthrex, and received Royalties from Wright Medical., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Patients with gastro-oesophageal adenocarcinoma with tumour-positive lymph nodes (ypN+) or positive surgical margins (R1) following neoadjuvant chemotherapy and resection are at high risk of recurrence. Adjuvant nivolumab is effective in oesophageal/oesophagogastric junction cancer and residual pathological disease following chemoradiation and surgery. Immune checkpoint inhibition has shown efficacy in advanced gastro-oesophageal cancer. We hypothesised that nivolumab/ipilimumab would be more effective than adjuvant chemotherapy in high-risk (ypN+ and/or R1) patients with gastro-oesophageal adenocarcinoma following neoadjuvant chemotherapy and resection., Patients and Methods: VESTIGE was an academic international, multicentre, open-label, randomised phase II trial evaluating the efficacy of adjuvant nivolumab/ipilimumab versus chemotherapy in gastro-oesophageal adenocarcinoma at high risk of recurrence. Patients were randomised 1 : 1 to receive standard adjuvant chemotherapy (same regimen as neoadjuvant) or nivolumab 3 mg/kg intravenously (i.v.) every 2 weeks plus ipilimumab 1 mg/kg i.v. every 6 weeks for 1 year. Key inclusion criteria included ypN+ and/or R1 status after neoadjuvant chemotherapy plus surgery. The primary endpoint was disease-free survival in the intent-to-treat population. Secondary endpoints included overall survival, locoregional and distant failure rates, and safety according to National Cancer Institute Common Terminology Criteria for Adverse Events v5.0., Results: The independent Data Monitoring Committee reviewed data from 189 of the planned 240 patients in June 2022 and recommended stopping recruitment due to futility. At the time of final analysis, median follow-up was 25.3 months for 195 patients (98 nivolumab/ipilimumab and 97 chemotherapy). Median disease-free survival for the nivolumab/ipilimumab group was 11.4 months [95% confidence interval (CI) 8.4-16.8 months] versus 20.8 months (95% CI 15.0-29.9 months) for the chemotherapy group, hazard ratio 1.55 (95% CI 1.07-2.25, one-sided P = 0.99). The 12-month disease-free survival rates were 47.1% and 64.0%, respectively. There were no toxicity concerns or excess early discontinuations., Conclusion: Nivolumab/ipilimumab did not improve disease-free survival compared with chemotherapy in patients with ypN+ and/or R1 gastro-oesophageal adenocarcinoma following neoadjuvant chemotherapy and surgery., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Digestive endoscopy is a highly dynamic medical discipline, with the recent adoption of new endoscopic procedures. However, comprehensive guidelines on the role of antibiotic prophylaxis in these new procedures have been lacking for many years. The Guidelines Commission of the French Society of Digestive Endoscopy (SFED) convened in 2023 to establish guidelines on antibiotic prophylaxis in digestive endoscopy for all digestive endoscopic procedures, based on literature data up to September 1, 2023. This article summarizes these new guidelines and describes the literature review that fed into them., Competing Interests: Conflict of Interest Competing interests in relation to the guidelines: None declared. Other competing interests: David Karsenti, MD: Consultant for Olympus, Covidien and Norgine; support for attending meetings from Alfasigma, Cook and Fujifilm. Rodica Gincul, MD: Consultant for Olympus; honoraria for lectures from Olympus; support for attending meetings from Celtrion, AbbVie. Arthur Belle, MD: Consultant for Boston Scientific; support for attending meeting from Mayoli. Geoffroy Vanbiervliet, MD-PhD: Consultant for Bostin Scientific and Ambu; honoraria for lectures, presentations and speeches from Pentax, Fujifilm, Tillots, and Norgine. Olivier Gronier, MD: Support for attending meetings from Dr Falk., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

We describe a method for planning total hip arthroplasty (THA) in patients with a displaced femoral neck fracture based on a simple CT scan protocol of the contralateral hip. This protocol was used on 22 consecutive patients during the inclusion period, followed by reconstruction and 2D templating to predict the implant size and positioning. The exact planned size was achieved in 21/22 (95%) cups, 14/22 (64%) femoral stems and 14/22 (64%) femoral heads. There were no intra- or postoperative fractures. After surgery in which this planning method had been applied, the differences in length and lateral offset were less than 5 mm on average relative to the opposite side (mean postoperative leg length difference of -2 mm (-8 to +3 mm) and lateralization of -4 mm (-14 to +3 mm)). While this technique exposes the patient to additional radiation, it does not require any specific devices or surgical approach and could be used in most hospitals. LEVEL OF EVIDENCE: IV., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Background: Evidence suggests that ctDNA may be a reliable biomarker to monitor metastatic colorectal cancer (CRC) evolution. Nevertheless, evidence on the potential of liquid biopsy in this setting is still low quality, mostly consisting of retrospective studies., Methods: COPERNIC is an international, multicenter clinical trial. The pilot study aims to confirm the predictive potential of early on-treatment ctDNA dynamics, and inform the design of a larger ctDNA-driven trial. Advanced CRC patients who are candidates for ≥3rd lines of systemic therapy undergo longitudinal blood sample collection during treatment (day 1, 15 and 29 for 2- or 4-weekly treatment regimens; day 1, 22 and 43 for 3-weekly treatment regimens) and at each imaging assessment. ctDNA analyses are carried out with the FoundationOne Liquid CDx and FoundationOneMonitor assays, and ctDNA changes during treatment are correlated with radiologic response (as assessed every 8-12 weeks by RECIST v1.1). The primary objective is to select the optimal timepoint and cut-off value for early ctDNA changes (at day 15/22) to predict progressive disease as best radiological response with a high positive predictive value. The cut-off value for ctDNA will be defined based on nonparametric ROC-curves with bootstrapping. Based on the expected rate of progressive disease and statistical assumptions, 109 patients are needed to be screened to have 87 assessable patients. COPERNIC is sponsored by the Institut Jules Bordet, and supported by Roche and Foundation Medicine. Recruitment is open in 13 centres across Belgium and France. The study is registered with clinicaltrials.gov (NCT05487248)., Competing Interests: Disclosure Giacomo Bregni: Support for travel/accomodation from Amgen. Marc Buyse: Stock ownership in International Drug Development Institute (IDDI), Louvain-la-Neuve, Belgium. Benoist Chibaudel: Consultancy, advisory roles, honoraria from Amgen, Bayer, Beigine, Biocartis, Lilly, Merck, MSD, Pfizer, Pierre Fabre, Roche, SeqOne, Sanofi, Servier, Takeda. Karen Geboes: Consultancy, advisory roles, honoraria from Amgen, BMS, Ipsen, MSD, Merck, Pierre Fabre, Servier. Research funding (institutional) from Merck, Ipsen, Servier. Support for travel/accomodation from Ipsen, Servier. Timon Vandamme: Consultancy, advisory roles, honoraria from AstraZeneca, Bayer, Bristol Myers Squibb, Eisai, Elmedix, Ipsen, Novartis, Roche, Sirtex. Research funding (institutional) from Ipsen and Novartis. Support for travel/accomodation from Ipsen and Servier. Alain Hendlisz: Consultancy, advisory roles, honoraria from Amgen, Bayer, Eli Lilly, Merck, Pierre Fabre, Servier, Sirtex. Research funding (institutional) from Amgen, Astra Zeneca, Ipsen, Leo Pharma, Merck, Roche, Sanofi, Teva Pharma. Support for travel/accomodation from Merck, Roche, Sirtex. Francesco Sclafani: Consultancy, advisory roles, honoraria from AMAL Therapeutics, Amgen, Bayer, BMS, Dragonfly Therapeutics, GSK, Merck, Nordic Pharma, Roche, Servier. Research funding (institutional) from Amgen, Astellas, Astra Zeneca, Bayer, BMS, Merck, MSD, Pierre-Fabre, Roche, Sanofi. Support for travel/accomodation from Amgen, Astra Zeneca, Bayer, Lilly, Merck, Roche, Servier. Leadership role: Secretary of the EORTC Gastrointestinal Tract Cancer Group., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Prior trials validated triplet chemotherapy (Tri-CT) with bevacizumab as first line treatment for metastatic colorectal cancer (mCRC) but real-world data are scarce and practices remain heterogeneous., Aims: To evaluate Tri-CT +/- bevacizumab efficacy and safety, and to identify factors influencing treatment decisions., Methods: The COLOTRIP retrospective study enrolled mCRC patients treated from 2014 to 2019 in 14 French centers., Results: Of 299 patients (81% PS 0-1, 58% RAS-mutated and 19% BRAF-mutated), 51% received Tri-CT and 49% Tri-CT + bevacizumab. Metastatic disease was classified as resectable (6.5%), potentially resectable (40%), and unresectable (54%). Bevacizumab use was associated with primary tumor location, mutational status and number of metastases. Median overall survival was 33.5 months in the Tri-CT group and 23.9 months in the Tri-CT + bevacizumab group, with median progression-free survival being 14.5 and 11.4 months. After adjusting for initial characteristics, no difference in survival was noted. Around 30% of patients experienced grade ≥3 adverse events., Conclusions: This study highlights several factors influencing Tri-CT use +/- bevacizumab decision and confirms the real-world good oncological outcomes and tolerability of these regimens in mCRC patients. Our results suggest that Tri-CT alone may by an appropriate option for specific subgroups of patients., Competing Interests: Conflict of interest Dr Philonenko has received honoraria as a speaker or in an advisory role for Servier, and travel grants from Mundi Farma and Pierre Fabre. Dr Artru has received honoraria in an advisory role for Roche, Merck-Serono, Amgen, and travel grants from Roche and Merck-Serono. Pr Lecomte has received personnel fees from Amgen, Merck Serono, Sanofi, Ipsen, Bayer, Astra Zeneca, BMS, Pierre Fabre and Servier. Pr Taieb has received honoraria as a speaker or in an advisory role from Astellas, Roche, Merck Serono, Amgen, Servier, Pierre Fabre, BMS, Astra Zeneca, Novartis, Takeda and MSD. Dr Coutzac has received honoraria as a speaker or in an advisory role from Amgen, Servier, Merck Serono, Bristol-Myers Squib, Merck Sharp and Dohme, Astra Zeneca, and Daiichi Sankyo. All other authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Achilles tendon (AT) disorders significantly impact patient life, necessitating accurate assessment tools. Current methods are often complex and time-consuming. This study aims to validate the Simple Ankle Value (SAV) for AT disorders., Methods: A multicenter study was conducted involving 101 participants, including a surgical, a conservative, and a control group. Participants completed the SAV, VISA-A, and EFAS scores. The study assessed correlations among scores, reliability, responsiveness to change, threshold and ceiling effect and discriminative ability of the SAV., Results: There was a significant strong correlation with the EFAS and a significant moderate to strong correlation with the VISA-A. The score showed excellent reliability (ρ = 0.95, 95 %CI: [0.913; 0.976], p < 0.001). Responsiveness to change was significant between preoperative and postoperative SAV (37.99 ± 25.73 vs 70.86 ± 21.26). The SAV discriminated between patient and controls with no threshold or ceiling effect., Conclusion: The SAV provides a valid, reliable, and responsive method for assessing AT disorders. It offers a simplified and effective alternative to more complex scores., Study Design: Cohort study (Diagnosis); Level of evidence, 2., (Copyright © 2024 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.)

PD-1/PD-L1 blockade has so far shown limited survival benefit for high-grade ovarian carcinomas. By using paired samples from the NeoPembrOv randomized phase II trial (NCT03275506), for which primary outcomes are published, and by combining RNA-seq and multiplexed immunofluorescence staining, we explore the impact of NeoAdjuvant ChemoTherapy (NACT) ± Pembrolizumab (P) on the tumor environment, and identify parameters that correlated with response to immunotherapy as a pre-planned exploratory analysis. Indeed, i) combination therapy results in a significant increase in intraepithelial CD8 + PD-1 + T cells, ii) combining endothelial and monocyte gene signatures with the CD8B/FOXP3 expression ratio is predictive of response to NACT + P with an area under the curve of 0.93 (95% CI 0.85-1.00) and iii) high CD8B/FOXP3 and high CD8B/ENTPD1 ratios are significantly associated with positive response to NACT + P, while KDR and VEGFR2 expression are associated with resistance. These results indicate that targeting regulatory T cells and endothelial cells, especially VEGFR2 + endothelial cells, could overcome immune resistance of ovarian cancers., (© 2024. The Author(s).)

This open-label, non-comparative, 2:1 randomized, phase II trial (NCT03275506) in women with stage IIIC/IV high-grade serous carcinoma (HGSC) for whom upfront complete resection was unachievable assessed whether adding pembrolizumab (200 mg every 3 weeks) to standard-of-care carboplatin plus paclitaxel yielded a complete resection rate (CRR) of at least 50%. Postoperatively patients continued assigned treatment for a maximum of 2 years. Postoperative bevacizumab was optional. The primary endpoint was independently assessed CRR at interval debulking surgery. Secondary endpoints were Completeness of Cytoreduction Index (CCI) and peritoneal cancer index (PCI) scores, objective and best response rates, progression-free survival, overall survival, safety, postoperative morbidity, and pathological complete response. The CRR in 61 pembrolizumab-treated patients was 74% (one-sided 95% CI = 63%), exceeding the prespecified ≥50% threshold and meeting the primary objective. The CRR without pembrolizumab was 70% (one-sided 95% CI = 54%). In the remaining patients CCI scores were ≥3 in 27% of the standard-of-care group and 18% of the investigational group and CC1 in 3% of the investigational group. PCI score decreased by a mean of 9.6 in the standard-of-care group and 10.2 in the investigational group. Objective response rates were 60% and 72%, respectively, and best overall response rates were 83% and 90%, respectively. Progression-free survival was similar with the two regimens (median 20.8 versus 19.4 months in the standard-of-care versus investigational arms, respectively) but overall survival favored pembrolizumab-containing therapy (median 35.3 versus 49.8 months, respectively). The most common grade ≥3 adverse events with pembrolizumab-containing therapy were anemia during neoadjuvant therapy and infection/fever postoperatively. Pembrolizumab was discontinued prematurely because of adverse events in 23% of pembrolizumab-treated patients. Combining pembrolizumab with neoadjuvant chemotherapy is feasible for HGSC considered not completely resectable; observed activity in some subgroups justifies further evaluation to improve understanding of the role of immunotherapy in HGSC., (© 2024. The Author(s).)

Introduction: The adoption of colorectal endoscopic submucosal dissection (ESD) is still limited in the West. A recent randomized trial showed that ESD is more effective and only slightly riskier than piecemeal endoscopic mucosal resection; reproducibility outside expert centers was questioned. We evaluated the results according to the annual case volume in a multicentric prospective cohort., Methods: Between September 2019 and September 2022, colorectal ESD was consecutively performed at 13 participating centers classified as low volume (LV), middle volume (MV), and high volume (HV). The main procedural outcomes were assessed. Multivariate and propensity score matching analyses were performed., Results: Three thousand seven hundred seventy ESDs were included. HV centers treated larger and more often colonic lesions than MV and LV centers. En bloc , R0, and curative resection rates were 95.2%, 87.4%, and 83.2%, respectively, and were higher at HV than at MV and LV centers. HV centers also achieved a faster dissection speed. Delayed bleeding and surgery for complications rates were 5.4% and 0.8%, respectively, without significant differences. The perforation rate (overall: 9%) was higher at MV than at LV and HV centers. Lesion characteristics, but not volume center, were independently associated with both R1 resection and perforation. However, after propensity score matching, R0 rates were significantly higher at HV than at LV centers, and perforation rates were significantly higher at MV than at HV centers., Discussion: Colorectal ESD can be successfully implemented in the West, even in nonexpert centers. However, difficult lesions must still be referred to experts., (Copyright © 2024 by The American College of Gastroenterology.)

Introduction: Tibial correction is often performed during a valgus-producing osteotomy for genu varum. However, overcorrection and the creation of a joint line obliquity (JLO) have been associated with unfavorable functional outcomes after high tibial osteotomy (HTO). The aims of this study were to analyze: 1) the corrections obtained after HTO; 2) the rationale behind the indication per the European Society for Sports Traumatology Surgery and Arthroscopy (ESSKA) recommendations; and 3) the correlation between the postoperative corrections obtained and functional outcomes., Hypothesis: A significant number of patients who underwent an isolated HTO did not present an "ideal" theoretical indication based on the preoperative angles and correction targets to be performed., Materials and Methods: This multicenter study included 289 isolated HTOs. Demographic and morphometric data were anonymized and compiled in a database. Preoperative radiographic parameters were compared with the ESSKA consensus recommendations on osteotomies for genu varum. The consensus defined the "ideal" indication for performing an HTO as medial tibiofemoral compartment pain with significant tibial varus deformity (medial proximal tibial angle [MPTA]<85°), no significant femoral varus deformity (lateral distal femoral angle [LDFA]<90°), an expected postoperative obliquity of less than 5°, and a correction resulting in moderate tibial valgus (postoperative MPTA<94°). The incidence of patients with an "ideal" theoretical indication for isolated HTO and those with a theoretical indication not perfectly justified by the radiographic data and preoperative planning were recorded., Results: Under the ESSKA consensus criteria, 25.3% (n=73) of isolated HTOs, 15.6% (n=45) of isolated femoral osteotomies, 9.3% (n=27) of double-level osteotomies, and 49.9% (n=144) of cases where no osteotomy was performed due to the lack of significant extra-articular tibial and/or femoral deformity were deemed justified. The presence of a preoperative femoral deformity and the absence of an "ideal" indication for HTO did not affect the postoperative Tegner Activity Scale or the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores (p>0.05). A high preoperative hip-knee-ankle (HKA) angle and MPTA, which indicated less varus, were associated with a greater risk of there being no "ideal" theoretical indication for an HTO (coefficient of determination [R 2 ]=0.19 and R 2 =1, respectively; p<0.001)., Conclusion: This study showed that isolated HTOs in current practice were not justified in a significant number of patients, even though they could lead to tibial overcorrection and excessive JLO. This did not impact the functional results of this series, but it might complicate the performance of a secondary knee arthroplasty. Nevertheless, some young patients in this series underwent a salvage osteotomy outside the "ideal" indications of the European recommendations., Level of Evidence: IV; case series., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

The treatment of rotational instability has been an intriguing challenge since the era of modern anterior cruciate ligament (ACL) surgery. Lateral extra-articular procedures (LEAPs) have emerged as a solution to this problem, particularly in high-risk populations. Several studies have shown significant benefits of combining LEAPs with ACL reconstruction, including reduced graft failure rates, improved knee stability, improved rotational stability, and higher return-to-play rates. These findings have led to an in-depth evaluation of LEAPs as lateral extra-articular tenodesis and anterolateral ligament reconstruction and their potential role in improving outcomes after ACL reconstruction., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The results of the PRODIGE 42/GERICO 12 study showed that short course radiotherapy had a better tolerance profile than radiochemotherapy, with comparable oncological results. We have included Quality of Life analyses and oncogeriatric evaluations in this study., Patients and Methods: In all, 101 patients ≥75 years of age with resectable T3-T4 rectal adenocarcinoma less than 12 cm from the anal margin received short course radiotherapy (5X5 Gy in one week) or radiochemotherapy (50 Gy, 2 y/f and capecitabine 800 mg/m 2 , 5 days/week) with delayed surgery (7 weeks ± 1) in both groups. The Quality of Life analyses (EORTC QLQ C-30 et ELD14) were conducted upon inclusion, pre-operatively, at 3, 6 and 12 months post-op, together with the oncogeriatric evaluations, including an evaluation of the IADL and ADL scores, walking speed, GDS15, MMSE, MNA., Results: We did not highlight any statistical difference for the global EORTC QLQ-C30 score; several factors are statistically in favor of the short course radiotherapy group at 3 months post-op (cognitive functions, fatigue, appetite). In the case of the ELD14 score, the disease burden is perceived as more negative at 3, 6 and 12 months postop in the radiochemotherapy group. The IADL score deteriorated in 44.8 % of the radiochemotherapy group and 14.8 % of the radiotherapy group (p = 0.032); similarly, the GDS15 depression score was better preserved in the short course radiotherapy group (p = 0.05). An analysis of the other scores: ADL, walking speed, MNA, MMSE did not highlight any statistical difference., Conclusion: Short course radiotherapy achieves better results in terms of Quality of Life and preservation of autonomy in patients aged ≥75 treated for locally advanced rectal cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Pemigatinib is approved for patients with pretreated, locally advanced or metastatic CCA harboring FGFR2 rearrangements or fusions. We aim to assess the effectiveness and safety of pemigatinib in real-world setting., Material and Methods: A joint analysis of two multicentre observational retrospective cohort studies independently conducted in France and Italy was performed. All consecutive FGFR2-positive patients affected by CCA and treated with pemigatinib as second- or further line of systemic treatment in clinical practice, within or outside the European Expanded Access Program, were included., Results: Between July 2020 and September 2022, 72 patients were treated with pemigatinib in 14 Italian and 25 French Centres. Patients had a median age of 57 years, 76% were female, 81% had ECOG-PS 0-1, 99% had intrahepatic CCA, 74% had ≥ 2 metastatic sites, 67% had metastatic disease at diagnosis, while 38.8% received ≥ 2 previous lines of systemic treatment. At data cut-off analysis (April 2023), ORR and DCR were 45.8% and 84.7%, respectively. Median DoR was 7 months (IQR: 5.8-9.3). Over a median follow-up time of 19.5 months, median PFS and 1-year PFS rate were 8.7 months and 32.8%. Median OS and 1-year OS rate were 17.1 months and 60.6%. Fatigue (69.4%), ocular toxicity (68%), nail toxicities (61.1%), dermatologic toxicity (41.6%) hyperphosphataemia (55.6%), stomatitis (48.6%), and diarrhea (36.1%) were the most frequent, mainly G1-G2 AEs. Overall incidence of G3 AEs was 22.2%, while no patient experienced G4 AE. Dose reduction and temporary discontinuation were needed in 33.3% and 40.3% of cases, with 1 permanent discontinuation due to AEs., Conclusions: These results confirm the effectiveness and safety of pemigatinib in a real-world setting., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

This systematic review aims to provide normative values for internal and external glenohumeral rotation strength in rugby players. From the inception to March 2021, the search strategy was (strength OR torque) AND shoulder AND rugby using PubMed, Scopus, Web of Science, and SPORTDiscus databases, with no language restrictions. This systematic review includes 15 articles involving 573 rugby players and presenting internal or external glenohumeral rotation strength values. Two main methods are used to assess glenohumeral rotation strength in rugby players: isokinetic and isometric methods; in the isometric method, the upper arm is abducted at either 0° or 90°. Owing to differences in isokinetic procedures and a lack of studies assessing isometric strength when the upper arm is in a neutral position, normative internal or external glenohumeral rotation strength values are only provided for isometric contractions when the upper arm is abducted at 90° based on 311 shoulders of 163 male rugby union players, with 2.04 ± 0.15 N.kg -1 and 2.11 ± 0.13 N.kg -1 for internal and external glenohumeral rotation strength, respectively. These findings may help strength and conditioning coaches and physical therapists, provide objective evidence when deciding whether or not rugby union players should return to sport., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

The knee is a joint that is often injured in sport, with a large and increasing number of ligament tears and repairs; postoperative complications can lead to poor outcome, such as stiffness. Beyond the well-known and well-described intra- and extra-articular causes of postoperative stiffness, the present study introduces the concept of a central reflex motor inhibition mechanism called arthrogenic muscle inhibition (AMI). AMI occurs after trauma and can be defined as active knee extension deficit due to central impairment of Vastus Medialis Obliquus (VMO) contraction, often associated with spinal reflex hamstring contracture. This explains the post-traumatic flexion contracture that is so common after knee sprain. The clinical presentation of AMI is easy to detect in consultation, in 4 grades from simple VMO inhibition to fixed flexion contracture by posterior capsule retraction in chronic cases. After recent anterior cruciate ligament (ACL) tear, more than 55% of patients show AMI, reducible in 80% of cases by simple targeted exercises initiated in consultation. Practically, in patients who have sustained knee sprain, it is essential to screen for this reflex mechanism and assess reducibility, as AMI greatly aggravates the risk of postoperative stiffness. In case of hemarthrosis, we recommend joint aspiration, which provides immediate benefit in terms of pain and motor inhibition. In case of persistent AMI, classical electrostimulation and "cushion crush", as used by all physiotherapists, are ineffective. To reduce the risk of postoperative stiffness, no surgery should be considered until AMI has resolved. LEVEL OF EVIDENCE: expert opinion., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Background: Endoscopic resection of adenomas prevents colorectal cancer, but the optimal technique for larger lesions is controversial. Piecemeal endoscopic mucosal resection (EMR) has a low adverse event (AE) rate but a variable recurrence rate necessitating early follow-up. Endoscopic submucosal dissection (ESD) can reduce recurrence but may increase AEs., Objective: To compare ESD and EMR for large colonic adenomas., Design: Participant-masked, parallel-group, superiority, randomized controlled trial. (ClinicalTrials.gov: NCT03962868)., Setting: Multicenter study involving 6 French referral centers from November 2019 to February 2021., Participants: Patients with large (≥25 mm) benign colonic lesions referred for resection., Intervention: The patients were randomly assigned by computer 1:1 (stratification by lesion location and center) to ESD or EMR., Measurements: The primary end point was 6-month local recurrence (neoplastic tissue on endoscopic assessment and scar biopsy). The secondary end points were technical failure, en bloc R0 resection, and cumulative AEs., Results: In total, 360 patients were randomly assigned to ESD ( n  = 178) or EMR ( n  = 182). In the primary analysis set ( n  = 318 lesions in 318 patients), recurrence occurred after 1 of 161 ESDs (0.6%) and 8 of 157 EMRs (5.1%) (relative risk, 0.12 [95% CI, 0.01 to 0.96]). No recurrence occurred in R0-resected cases (90%) after ESD. The AEs occurred more often after ESD than EMR (35.6% vs. 24.5%, respectively; relative risk, 1.4 [CI, 1.0 to 2.0])., Limitation: Procedures were performed under general anesthesia during hospitalization in accordance with the French health system., Conclusion: Compared with EMR, ESD reduces the 6-month recurrence rate, obviating the need for systematic early follow-up colonoscopy at the cost of more AEs., Primary Funding Source: French Ministry of Health., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M23-1812.

Introduction: Although an autogenous graft has the highest rate of bone union to fill the void created in medial opening wedge high tibial osteotomy (MOWHTO), it also has some disadvantages, such as prolonged surgical time, donor site pain and morbidity. Two possible candidates for ideal grafts to replace autogenous grafts are allogeneic and synthetic graft, which are free from donor site pain and morbidity. However, previous reports comparing the clinical results of allogeneic to synthetic graft have been limited and controversial. The purpose of this study is to compare radiological findings and clinical outcomes of using synthetic versus allogenic graft to fill the void created in MOWHTO., Hypothesis: The present clinical study hypothesized that allogenic graft to fill the void would allow the higher rate of bone union and better clinical outcomes., Material and Methods: This study compared the clinical and radiological outcomes of 95 patients who received MOWHTO to fill the void with either synthetic or allogenic graft (44 in Syn group, 51 in Allo group). Preoperatively and postoperatively, all patients were clinically evaluated; Return to work, Tegner activity score, and the Western Ontario and Macmaster University scores were reported. Radiographically, osteoarthritis grade and pre- and postoperative parameters were reported, including Hip-knee-ankle angle, mechanical lateral distal femoral angle, medial proximal tibial angle, joint line convergence angle, proximal posterior tibial angle, and limb length discrepancy. Perioperative details and complications were also reported., Results: Mean follow-up (months) were 24.0±1.3 in Syn group and 26.8±1.2 in Allo group (p=0.13). The postoperative improvement of pain and global WOMAC scores in Allo group were significantly better than in Syn group (ΔPain of WOMAC: Syn group 27.8±4.4, Allo group 49.3±3.8, p value <0.001*) (ΔGlobal score of WOMAC: Syn group 16.7±3.2, Allo group 37.4±4.9, p value=0.002*). The risk of hinge fracture in Syn group was significantly higher than in Allo group (Hinge fracture by Takeuchi grade (0/1/2/3): Syn group 37/3/3/1, Allo group 43/8/0/0, p value=0.04*). The timing of full weight bearing in Allo group was significantly earlier than in Syn group (Weight Bearing (1=FWB, 2=PWB 3wk, 3=PWB 6wk): Syn group 2.7±0.1, Allo group 2.3±0.1, p value=0.01*)., Discussion: The use of allogenic graft to fill the void in MOWHTO does not show superiority in bone union compared to synthetic graft, however it improves pain, function, decreases the risk of hinge fracture and allows faster weight bearing than synthetic graft., Level of Proof: III; Case-control study., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

INTRODUCTION : Residual colorectal neoplasia (RCN) after previous endoscopic mucosal resection is a frequent challenge. Different management techniques are feasible including endoscopic full-thickness resection using the full-thickness resection device (FTRD) system and endoscopic submucosal dissection (ESD). We aimed to compare the efficacy and safety of these two techniques for the treatment of such lesions. METHODS : All consecutive patients with RCN treated either using the FTRD or by ESD were retrospectively included in this multicenter study. The primary outcome was the R0 resection rate, defined as an en bloc resection with histologically tumor-free lateral and deep margins. RESULTS : 275 patients (median age 70 years; 160 men) who underwent 177 ESD and 98 FTRD procedures for RCN were included. R0 resection was achieved in 83.3 % and 77.6 % for ESD and FTRD, respectively ( P  = 0.25). Lesions treated by ESD were however larger than those treated by FTRD ( P  < 0.001). The R0 rates for lesions of 20-30 mm were 83.9 % and 57.1 % in the ESD and FTRD groups, respectively, and for lesions of 30-40 mm were 93.6 % and 33.3 %, respectively. On multivariable analysis, ESD procedures were associated with statistically higher en bloc and R0 resection rates after adjustment for lesion size ( P  = 0.02 and P  < 0.001, respectively). The adverse event rate was higher in the ESD group (16.3 % vs. 5.1 %), mostly owing to intraoperative perforations. CONCLUSION:  ESD is effective in achieving R0 resection for RCN whatever the size and location of the lesions. When residual lesions are smaller than 20 mm, the FTRD is an effective alternative., Competing Interests: C. Yzet has received consultancy and lecture fees from Abbvie, Takeda, Jansen, Amgen, and Galapagos. Y. Le Baleur has provided training sessions for Ovesco Endoscopy AG. J. Jacques has provided ESD training sessions for Olympus, Fuji, Erbe, Pentax, and Lumendi and has received lecture fees from Abbvie, Janssen, and Norgine. M. Barret is on the boards of Norgine and Ambu, and has received research grants from Pentax. M. Shaefer has provided training sessions for Boston Scientific, and has received congress invitations from Olympus, Cook, Cousin Medical, Boston Scientific, Pentax, Abbvie, MSD, Amgen, and Norgine. S. Leblanc has received consulting and lecture fees from Norgine, Olympus, Alfasigma, and Ovesco. J. Rivory has provided training sessions in endoscopy and endoscopic resection for Olympus, and Cook Medical.E. Coron had a speaker's and consultancy agreement with Fujifilm. G. Vanbiervliet has provided consultancy for Boston Scientific, Cook Medical, Fujifilm Inc., and Ambu, and has provided expert lectures/medical training for Boston Scientific, Cook Medical, Mayloy Spindler, Pentax Inc., Fujifilm Inc., and Tillotts. M. Pioche has provided training sessions in endoscopy and endoscopic resection for Olympus, Cook Medical, Boston Scientific, and Pentax Medical, and in endoscopic characterization with Norgine and Provepharm; he received an invitation to UEGW from AlfaSigma; he holds a patent with his institution, Hospices civils de Lyon, for the IPEFIX device.J. Albouys, P. Mandengue, E. Abou Ali, J.-B. Chevaux, V. Lepillez, J. Privat, T. Degand, T. Wallenhorst, U. Chaput, A. Berger, K. Aziz, G. Rahmi, E. Kull, L. Caillo, S. Koch, and F. Subtil declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background: An increased posterior tibial slope (PTS) is a proven risk factor for both native anterior cruciate ligament (ACL) and ACL graft insufficiency. Anterior closing wedge high tibial osteotomy (ACW-HTO) for PTS correction is a validated procedure in revision ACL reconstruction (ACLR)., Purpose/hypothesis: The aim of this study was to evaluate the effect of combined ACW-HTO and at least a second revision ACLR procedure on knee stability, function, and sports performance in a large series of patients. The hypothesis was that patients would return to impact sports after ACW-HTO combined with a second or third revision ACLR procedure., Study Design: Case series; Level of evidence, 4., Methods: A total of 64 patients who underwent a second (or more) revision ACLR procedure and ACW-HTO between June 1, 2015, and June 1, 2019, and had a PTS >12° were included. The mean age was 29.60 ± 6.31 years, and the mean preoperative PTS was 13.79°± 1.50°. The cases were analyzed at a mean follow-up of 2.96 ± 0.83 years (range, 2-5 years). At the last follow-up, the rate of patients returning to impact sports (based on the University of California, Los Angeles [UCLA], activity scale), ACL graft status (per magnetic resonance imaging), International Knee Documentation Committee (IKDC) scores, Lysholm scores, and laxity measurements using a knee arthrometer were recorded., Results: The total number of patients participating in impact sports and high-impact sports was as follows: 43 and 30, respectively, before the injury; 0 and 0, respectively, preoperatively; and 31 and 12, respectively, postoperatively. At the last follow-up, the UCLA score was ≥8 in 48.44% of the patients, and only 16 patients returned to their preinjury level of activity. At a minimum of 2 years of follow-up, there was clinical improvement in the IKDC score from 37.98 ± 12.48 preoperatively to 69.06 ± 12.30 postoperatively ( P < .0001), in the Lysholm score from 51.94 ± 14.03 preoperatively to 74.45 ± 11.44 postoperatively ( P < .001), and in the UCLA score. However, this clinical improvement did not equate to preinjury values for all outcome scores ( P < .001). The preinjury IKDC and Lysholm scores were 76.98 ± 11.71 and 89.26 ± 8.91, respectively. The mean change in anterior knee laxity using a knee arthrometer at 134 and 250 N was -4.03 ± 0.18 mm and -3.63 ± 0.16, respectively. There were 3 cases of a rerupture with a severe pivot shift on the clinical examination. None of these patients underwent revision per the patient's preference. Increased knee recurvatum was observed in one-third of the patients, but all were asymptomatic., Conclusion: In the setting of chronic ACL-deficient knees, PTS reduction (ACW-HTO) with revision ACLR restored knee stability and improved function with an acceptable rate of specific complications. Increased knee recurvatum was observed in one-third of the patients, but all were asymptomatic. Also, approximately half of the patients were able to return to impact sports., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: M.O. has received consulting fees from Newclip Technics, Arthrex, and Stryker. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

Background: Multiligament knee injuries involving the medial side are common. When performing surgical reconstruction, use of the medial hamstrings (HS) as grafts remains controversial in this setting., Purpose: To determine the role of the medial HS in stabilizing the valgus knee for different types of medial-sided knee injury., Study Design: Controlled laboratory study., Methods: A biomechanical study on 10 cadaveric knees was performed. Valgus load (force moment of 10 N/m) was applied at 0°, 30°, and 60° of flexion, and the resultant rotation was recorded using an optoelectronic motion analysis system. Measurements were repeated for 4 different knee states: intact knee, superficial medial collateral ligament (sMCL) injury, deep medial collateral ligament (dMCL) injury, and posterior oblique ligament (POL) injury. For each state, 4 loading conditions (+ loaded; - unloaded) of the semitendinosus (ST) and gracilis (GRA) tendons were tested: ST+/GRA+, ST+/GRA-, ST-/GRA+, and ST-/GRA-., Results: At 0° of flexion, combined unloading of the ST and GRA (ST-/GRA-) increased valgus laxity on the intact knee compared with the ST+/GRA+ condition ( P < .05). For all medial-sided injury states (isolated sMCL; combined sMCL and dMCL; and combined sMCL, dMCL, and POL damage), ST-/GRA- increased valgus laxity at 0° and 30° of flexion versus ST+/GRA+ ( P < .05 for all). The absolute value of valgus laxity increased with the severity of medial-sided ligament injury. Isolated ST unloading increased valgus laxity for the intact knee and the MCL-injured knee (combined sMCL and dMCL) at 0° of flexion ( P < .05 vs ST+/GRA+). Isolated unloading of the GRA had no effect on valgus knee stability., Conclusion: The medial HS tendons contributed to the stabilization of the knee in valgus, and this was even more important when the medial side was severely affected (POL damage). This stabilizing effect was greater between 0° and 30°, in which the POL is the main valgus stabilizer., Clinical Relevance: When deciding on graft selection for multiligament knee injury reconstruction, the surgeon should be aware of the effect of harvesting the medial HS tendon on valgus laxity., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: A.K. has received consulting fees from Stryker and speaking fees from Implantcast. R.P. has received consulting fees from Lepine. B.S.-C. has received consulting fees and royalties from Arthrex. T.N. has received consulting fees from Lepine. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto. Ethical approval was not sought for the present study., (© The Author(s) 2023.)

Introduction: Sequential anti-programmed cell death protein 1 (PD-1) or anti-programmed death-ligand 1 (PD-L1) followed by small targeted therapy use is associated with increased prevalence of adverse events (AEs) in NSCLC. KRASG12C inhibitor sotorasib may trigger severe immune-mediated hepatotoxicity when used in sequence or in combination with anti-PD-(L)1. This study was designed to address whether sequential anti-PD-(L)1 and sotorasib therapy increases the risk of hepatotoxicity and other AEs., Methods: This is a multicenter, retrospective study of consecutive advanced KRAS G12C -mutant NSCLC treated with sotorasib outside clinical trials in 16 French medical centers. Patient records were reviewed to identify sotorasib-related AEs (National Cancer Institute Common Classification Criteria for Adverse Events-Version 5.0). Grade 3 and higher AE was considered as severe. Sequence group was defined as patients who received an anti-PD-(L)1 as last line of treatment before sotorasib initiation and control group as patients who did not receive an anti-PD-(L)1 as last line of treatment before sotorasib initiation., Results: We identified 102 patients who received sotorasib, including 48 (47%) in the sequence group and 54 (53%) in the control group. Patients in the control group received an anti-PD-(L)1 followed by at least one treatment regimen before sotorasib in 87% of the cases or did not receive an anti-PD-(L)1 at any time before sotorasib in 13% of the cases. Severe sotorasib-related AEs were significantly more frequent in the sequence group compared with those in the control group (50% versus 13%, p < 0.001). Severe sotorasib-related AEs occurred in 24 patients (24 of 48, 50%) in the sequence group, and among them 16 (67%) experienced a severe sotorasib-related hepatotoxicity. Severe sotorasib-related hepatotoxicity was threefold more frequent in the sequence group compared with that in the control group (33% versus 11%, p = 0.006). No fatal sotorasib-related hepatotoxicity was reported. Non-liver severe sotorasib-related AEs were significantly more frequent in the sequence group (27% versus 4%, p < 0.001). Severe sotorasib-related AEs typically occurred in patients who received last anti-PD-(L)1 infusion within 30 days before sotorasib initiation., Conclusions: Sequential anti-PD-(L)1 and sotorasib therapy are associated with a significantly increased risk of severe sotorasib-related hepatotoxicity and severe non-liver AEs. We suggest avoiding starting sotorasib within 30 days from the last anti-PD-(L)1 infusion., (Copyright © 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Endoscopic submucosal dissection (ESD) is challenging for appendicular lesions. We report the outcomes of ESD in this context., Methods: We collected data of ESD procedures for appendiceal neoplasia in a multicenter prospective registry. Main study endpoints were R0, en-bloc, and curative resection rates and adverse event rate., Results: One hundred twelve patients were included, 47 (42%) with previous appendectomy. Fifty-six (50%) were Toyonaga type 3 lesions (15 [13.4%] postappendectomy). En-bloc and R0 resection rates were 86.6% and 80.4%, respectively, with no significant difference associated with different grades of appendiceal invasion (P = .9 and P = .4, respectively) or previous appendectomy (P = .3 for both). The curative resection rate was 78.6%. Additional surgery was performed in 16 cases (14.3%), including 10 (62.5%) Toyonaga type 3 lesions (P = .04). This included the treatment of 5 cases (4.5%) of delayed perforation and 1 acute appendicitis., Conclusions: ESD for appendicular lesions is a potentially safer and effective alternative to surgery for a significant proportion of patients., (Copyright © 2023 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background: Small bowel adenocarcinoma is a rare cancer, and the role of adjuvant chemotherapy for localized disease is still debated., Methods: This retrospective multicenter study included all consecutive patients who underwent curative surgical resection for localized small bowel adenocarcinoma between 1996 and 2019 from 3 French cohort studies. Prognostic and predictive factors of adjuvant chemotherapy efficacy were analyzed for disease-free survival and overall survival. The inverse probability of treatment weighting method was applied in the Cox regression model using the propensity score derived from multivariable logistic regression., Results: A total of 354 patients were included: median age, 63.5 years; duodenum location, 53.5%; and tumor stage I, II, and III in 31 (8.7%), 144 (40.7%), and 179 (50.6%) patients, respectively. The adjuvant chemotherapy was administered in 0 (0%), 66 (48.5%), and 143 (80.3%) patients with stage I, II, and III, respectively (P < .0001). In the subgroup analysis by inverse probability of treatment weighting method, a statistically significant disease-free survival and overall survival benefit in favor of adjuvant chemotherapy was observed in high-risk stage II (T4 and/or <8 lymph nodes examined) and III (T4 and/or N2) but not for low-risk stage II (T3 and ≥8 lymph nodes examined) and III (T1-3/N1) tumors (Pinteraction < .05). Furthermore, tumor location in jejunum and ileum was also a statistically significant predictive factor of response to adjuvant chemotherapy in stage II and III tumors (Pinteraction < .05)., Conclusion: In localized small bowel adenocarcinoma, adjuvant chemotherapy seems to provide a statistically significant survival benefit for high-risk stage II and III tumors and for jejunum and ileum tumor locations., (© The Author(s) 2023. Published by Oxford University Press.)

Purpose: Baseline circulating tumour DNA (ctDNA) is a potential prognostic marker in metastatic colorectal cancer (mCRC) patients. However, few studies have compared ctDNA with the usual prognostic factors, and no ctDNA cut-off has been proposed for daily use in clinical practice., Patients and Methods: Chemotherapy-naive patients with mCRC were prospectively included. Plasma samples were collected at diagnosis and analysed centrally by both NGS and methylation digital PCR. Baseline patient and disease characteristics, treatment regimens, and secondary surgeries were collected. The restricted cubic spline method was used to define the optimal cut-off of ctDNA mutated allelic frequency (MAF). Prognostic values were assessed on overall survival (OS) using Cox models., Results: From July 2015 to December 2016, 412 patients were included. ctDNA was undetectable in 83 patients (20%). ctDNA was an independent prognostic marker for OS considering the whole study population. The optimal cut-off for ctDNA MAF was 20% with median OS of 16.0 and 35.8 months for patients with MAF ≥20% and<20%, respectively (hazard ratio = 0.40; 95% confidence intervals: 0.31-0.51; P < 0.0001). The independent prognostic value of ctDNA MAF at 20% was confirmed in subgroups defined by RAS/BRAF status or resectability of metastases. Combining ctDNA MAF and carcinoembryonic antigen levels allowed us to define three different prognostic groups with median OS of 14.2, 21.1, and 46.4 months (P < 0.0001)., Conclusion: ctDNA with a MAF cut-off of 20% improves prognostication of chemotherapy-naïve mCRC patients and may be useful in the future for individualised therapeutic decisions and as a stratification factor in clinical trials., Trial Registration: Clinicaltrials.gov, NCT02502656., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: J.B. Bachet has received personal fees from Amgen, Bayer, Bristol Myers Squibb, Merck Serono, Merck Sharp & Dohme, Pierre Fabre, Sanofi, Servier, and non-financial support from Amgen, Merck Serono, and Roche, outside the submitted work. P. Laurent-Puig has received grants from AGEO during the conduct of the study; personal fees from Amgen, Biocartis, Merck Serono, Astrazeneca, Sanofi, Pierre Fabre, MSD, outside the submitted work. O. Bouché has received personal fees from Merck Serono, Amgen, Bayer, Apmomia Therapeutics, MSD, Servier and Pierre Fabre, outside the submitted work. V. Taly has received honoraria from Raindance Technologies during the conduct of the study, and honoraria from Boehringer Ingelheim, outside the submitted work. P. Artru has received personal fees from Merck Serono during the conduct of the study; personal fees from Roche, Sanofi, Celgene, Sanofi, outside the submitted work. D. Tougeron has received personal fees from Amgen, MSD, BMS, Merck Serono, Pierre Fabre, Servier, Sirtex, Ipsen, Roche, outside the submitted work. T. Lecomte has received personnel fees from Amgen, Merck Serono, Sanofi, Ipsen, Bayer, Pierre Fabre and Servier, outside the submitted work. F. Mary has received personal fees from Bayer, Amgen, Merck Serono and Ipsen, outside the submitted work. T. Aparicio has received personal fees from Bristol Myers Squibb, Pierre Fabre, Servier, Amgen, Merck Sharp & Dohme, Sirtex, outside the submitted work. L. Marthey has received personal fees from Roche, personal fees and non-financial support from Takeda, non-financial support from Amgen and Novartis, outside the submitted work. H. Blons has received personal fees from Astra-Zeneca, Merck Serono, Amgen, Boehringer Ingelheim and Pfizer, outside the submitted work. D. Vernerey has received personal fees from HalioDx, outside the submitted work. J. Taieb has received honoraria for speaker or advisory role from BMS, Roche, Merck Serono, Amgen, Servier, Pierre Fabre, Astra Zeneca and MSD, outside the submitted work. A. Meurisse, L. Mas, J.M. Gornet, R. Cohen, S. Louafi, A.Thirot-Bidault, I. Baumgaertner, R. Coriat declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Purpose: The purpose was to estimate the prevalence of popliteus tendon impingement following TKA, and to describe the characteristics and the differential diagnosis protocol for this rare condition. The hypothesis was that arthroscopic popliteal tenotomy in TKA patients with suspected popliteus tendon impingement would relieve pain and improve satisfaction., Methods: Of 741 TKAs performed over three years, eight (1.1%, all women) had suspected popliteus tendon impingement, of which seven had severe localised posterolateral knee pain and one global knee pain. Upon confirmation of popliteus tendon impingement, arthroscopic popliteal tenotomy was performed, and outcomes (Pain on visual analogue scale (pVAS; best, 0; worst, 10), Oxford Knee Score (OKS; best, 48; worst, 0) and satisfaction (best, 100%; worst, 0%) assessed at mean 18-month follow-up., Results: At four to 30 months after TKA, arthroscopic exploration revealed popliteus tendon impingement in all eight knees. Six reported complete pain relief (pVAS, 0) the day following arthroscopic popliteal tenotomy, whilst one reported some residual pain (pVAS, 2). The remaining patient with global pain reported no pain relief, and required revision TKA at 12 months. Excluding the revised TKA, OKS was between 19 and 43, and satisfaction was rated ≥ 80% in five of the remaining seven patients., Conclusions: Arthroscopic popliteal tenotomy relieved symptoms in TKA patients with persistent localised posterolateral pain and a positive popliteus test. These findings suggest that the popliteus test is reliable to diagnose popliteus tendon impingement following TKA, which could be treated by arthroscopic popliteal tenotomy., Level of Evidence: Level IV, Small case series., (© 2023. The Author(s) under exclusive licence to European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA).)

Purpose: Metastatic endocrine-resistant breast cancer (MBC) is a disease with poor prognosis and few treatment options. Low lymphocyte count is associated with limited overall survival. In a prospective cohort of lymphopenic patients with HER-2 negative MBC, we assessed the clinical and biological impact of pembrolizumab combined with metronomic cyclophosphamide., Experimental Design: This multicenter Phase II study evaluated the safety and clinical activity of pembrolizumab (intravenous (IV), 200mg, every 3 weeks) combined with metronomic cyclophosphamide (50mg/day, per os) in lymphopenic adult patients with HER2-negative MBC previously treated by at least one line of chemotherapy in this setting according to a Simon's minimax two-stage design. Blood and tumor samples were collected to assess the impact of the combined treatment on circulating immune cells and the tumor immune microenvironment through multiparametric flow cytometry and multiplex immunofluorescence analyses. Primary endpoint was the clinical benefit rate at 6 months of treatment (CBR-6M). Secondary endpoints were objective response rate (ORR), duration of response, progression free survival (PFS), and overall survival (OS)., Results: Two out of the twenty treated patients presented clinical benefit (one Tumor Mutational Burden (TMB)-high patient with complete response (CR) and one patient with objective response (OR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST V1.1) associated with a strong increase of cytokine-producing and proliferating CD4 + T cells and higher CD8 + T cells to macrophage ratios in the tumor. This impact on CD4 + and CD8 + T cell polyfunctionality was still observed more than one year for the patient with CR. A decreased in their absolute number of CD4 + and CD8 + memory T cells was observed in other patients., Conclusion: Pembrolizumab combined with metronomic cyclophosphamide was well tolerated, and displayed limited anti-tumoral activity in lymphopenic MBC. Correlative translational data of our trial advocates for additional studies with other chemotherapy combinations., Competing Interests: Benoîte Mery and Christine Ménétrier-Caux are co-first authors for this study. Bertrand Dubois and Olivier Trédan are co-last authors for this study. Dr Pierre-Etienne Heudel reports personal fees, non-financial support from PFIZER, GILEAD, NOVARTIS, SEAGEN, LILLY; personal fees from MSD, during the conduct of the study. Professor Isabelle Ray-Coquard reports grants, personal fees from MSD and BMS; personal fees from Astra ZENECA, GSK, CLOVIS, ROCHE, DAICHI, MERSANA, Immunogen, Pharmamar, during the conduct of the study. Dr Thomas Bachelot reports grants, personal fees, non-financial support from Novartis, AstraZeneca, Daiichi, Pfizer; grants, personal fees from SeaGen, outside the submitted work. Dr Paule Augereau reports personal fees, non-financial support from AstraZeneca, GSK, Seagen; personal fees from Novartis, outside the submitted work. Dr David Perol reports personal fees, travel funding from ROCHE, personal fees from TAKEDA, ASTRAZENECA, BAYER, BOEHRINGHER-INGELHEIM, BRISTOL-MYERS SQUIBB, DAIICHI-SANKYO, ELI-LILLY, IPSEN, NOVARTIS, MERCK SHARP AND DOHME, JANSSEN, PFIZER, outside the submitted work. Dr Olivier Trédan reports grants, personal fees from MSD, during the conduct of the study. The authors report no other conflicts of interest in this work., (© 2023 Mery et al.)