Outcomes of resection for colorectal cancer hepatic metastases stratified by evolving eras of treatment

<p>Abstract</p> <p>Background and purpose</p> <p>The outcomes and management of colorectal cancer (CRC) hepatic metastasis have undergone many evolutionary changes. In this study, we aimed to analyze the outcomes of patients with CRC hepatic metastasis in terms of the era of treatment.</p> <p>Methods</p> <p>We conducted a retrospective review of 279 patients who underwent liver resection (LR) for CRC hepatic metastases. The prognoses of patients treated pre-2003 (era 1) and post-2003 (era 2) were examined.</p> <p>Results</p> <p>Of the patients included in the study, 210 (75.3%) had CRC recurrence after LR. There was a significant difference in the ratio of CRC recurrence between the 2 eras (82.0% in era 1 <it>vs</it>. 69.5% in era 2; <it>p </it>= 0.008). Analysis of recurrence-free and overall survival rates also showed that the patient outcome was significantly better in the post-2003 era than in the pre-2003 era. Further analysis showed that a significantly higher percentage of patients in era 2 had received modern chemotherapeutic regimens including irinotecan and oxaliplatin, while patients in era 1 were mainly administered fluorouracil and leucovorin for adjuvant chemotherapy. Among patients with CRC recurrence, a significant ratio of those in era 2 underwent surgical resection for recurrent lesions, and these patients had a better survival curve than did patients without resection (34.1% <it>vs</it>. 2.2% for 5-year survival; <it>p </it>< 0.0001).</p> <p>Conclusion</p> <p>The incidence of CRC recurrence after LR for hepatic metastasis remains very high. However, the management and outcomes of patients with CRC hepatic metastasis have greatly improved with time, suggesting that the current use of aggressive multimodality treatments including surgical resection combined with modern chemotherapeutic regimens effectively prolongs the life expectancy of these patients.</p

Whether we design: A weather report

The following report summarises a conversation between staff and students about the weather and design at a School of Design PhD seminar at the Royal College of Art on 16th February and 9th March 2023. A Strange Weather, A Strange Word. Very often, the words climate and weather are used interchangeably. It would seem that both terms stem from the same root, but this is not the case. Climate comes from the late Latin clima and the Greek klima, meaning ‘slope’ or ‘lean’. Wither, or weather, instead, comes from the Germanic root linked to ‘wind’ (Cresswell, 2021). Regardless of their roots, the interdependence between climate and weather might be why the meaning of climate has significantly changed over the years. At first, climate meant a “zone of the earth between two lines of latitude”. Later, it was referred to as earth’s “atmospheric conditions” (ibid.). Today, the climate is conceptualised as “an integrated biogeophysical system highly vulnerable to human interference” (Dryzek, 2022). Strangely, as we begin to perceive weather as both vulnerable and extreme, weather and climate will likely mean something entirely different for future generations

Results of surgical treatment of lung metastases from colorectal cancers

The aim of this work was to determine the long term results and the prognostic factors after surgical resection of pulmonary metastases from colorectal cancer

The inflammasome of tumor cells modulates the biology of tumor-infiltrating T lymphocytes in colorectal cancer

International audienceIn colorectal cancer (CRC), little is known about mechanisms by which tumor cells can influence the biology of Tumor Infiltrating T lymphocytes (TILs) present in the tumor microenvironment. One of these mechanisms could be modulation of the inflammasome of tumor cells. The inflammasome is a molecular platform present in normal intestinal epithelial cells, whose effector protein, caspase-1, can rapidly mature IL-18 and generate a mucosal Th1 (IFNγ) response. However, the inflammasome status of tumor cells in CRC and its potential role in the biology of TILs are unknown yet. This prospective study aimed to determine in CRC patients (n = 50) : i) the status of the inflammasome (caspase-1 / IL-18 axis) in tumor cells according to their microsatellite status [unstable (MSI) or stable (MSS)], in relation with the density of Th1/Tc1 TILs (T-bet+) and with the levels of the prototype Th1 cytokine IFNγ, secreted in an ex vivo explant culture model of CRC we developed and ii) the impact of the inflammasome-dependent cytokines potentially secreted by tumor cells on the biology of isolated TILs. Our study delineates two major groups of patients. The first group (33% of cases, mostly MSS with a low immunoscore) featured no active caspase-1 in tumor cells, no or low levels of mature IL-18 and IFNγ and only few T-bet+ TILs in the tumor microenvironment. This profile could correspond to an immune escape mechanism facilitating tumor progression. The second group (66% of cases, both MSI and MSS with high immunoscore) featured active caspase-1 in tumor cells associated with mature IL-18 secretion, high density of T-bet+ TILs expressing IL-18Rα and IFNγ release in most cases. In addition, isolated IL-18Rα+ TILs cultured with recombinant IL-18 were able to secrete IFNγ, either left unstimulated or stimulated with anti-CD3. In these CRC, the inflammasome of tumor cells, maintained and active, can contribute to a Th1/Tc1 antitumor response elicited by TILs present in the microenvironment that can modulate tumor growth. Interestingly, in a few cases of this second group (MSI CRC), the numerous T-bet+ TILs were unable to generate a Th1 response. Noticeably, these TILs express numerous immune checkpoints including PD1 and TIGIT, potentially responsible for their exhaustion. This study is the first to delineate functional interactions between tumor cells and TILs in CRC, using ex vivo explant cultures. Altogether, our findings support the inflammasome of tumor cells as a potential new therapeutic target to strengthen the Th1/Tc1 immune response in CRC, in association with immune checkpoint blockers. This work is supported by the “Ligue contre le Cancer Grand Ouest”Citation Format: Linda Bilonda, Delphine Dansette, Cecile Deleine, Romain Oger, Nicolas Jouand, Juliette Podevin, Pierre Fourquier, Emilie Thibaudeau, Jerome Chetritt, Jean-François Mosnier, Celine Bossard, Nadine Gervois, Anne Jarry. The inflammasome of tumor cells modulates the biology of tumor-infiltrating T lymphocytes in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4061

Assessing the accuracy of a new hand hygiene monitoring device (SmartRub®): from the laboratory to clinical practice

Background: We developed SmartRub® powered by iQati®, an electronic device composed of a wristband and an alcohol-based handrub pocket-sized dispenser that measures and provides feedback on the duration of hand friction and the volume poured during each hand hygiene action. We aimed to assess the accuracy of SmartRub®. Methods: The specificity, sensitivity, positive and negative predictive values (PPV and NPV) of SmartRub® were assessed in a 3-phased experiment: (1) laboratory-controlled conditions with volunteers; (2) pre-planned clinical path with volunteers and (3) real clinical conditions with healthcare workers. The accuracy of SmartRub® was evaluated by quantifying its ability to correctly capture true hand hygiene actions and to not record other actions performed while wearing the device. Results: In the laboratory, 7 volunteers performed 816 actions. Overall sensitivity was 94.1% (95% CI 91.4-96.2%) with a PPV of 99.0% (95% CI 97.3-99.6%) and specificity was 99.0% (95% CI 97.5-99.7%) with a NPV of 94.4% (95% CI 91.9-96.1%). During the pre-planned clinical path phase, 13 volunteers performed 98 planned paths and a total of 967 actions were performed. Overall sensitivity was 94.6% (95% CI 92.2-96.5%) with a PPV of 84.3% (95% CI 81.6-86.7%) and specificity was 82.4% (95% CI 78.7-85.7%) with a NPV of 93.9% (95% CI 91.3-95.7%). During the real clinical conditions phase, 17 healthcare workers were observed for a total of 15 h and 3 min while they performed 485 actions. Sensitivity was 96.8% (95% CI 93.8-98.6%) with a PPV of 98.3% (95% CI 95.6-99.3%) and specificity was 98.3% (95% CI 95.7-99.5%) with a NPV of 96.8% (95% CI 93.9-98.4%). Conclusions: Smartrub® is a highly reliable device for capturing hand hygiene actions under a range of conditions, from the laboratory to clinical care activities.</p

Intraepithelial CD94+ tumor-infiltrating lymphocytes in a context of HLA-E overexpression as a new immune checkpoint to predict prognosis in colorectal carcinomas.

International audienceBackground: A better understanding of the immune-modulating interactions between tumor cells and immune cells underlying the balance between immune control and immune resistance in colorectal cancer (CRC) is crucial for the design of immunotherapies. We have previously demonstrated that overexpression of the human MHC class Ib molecule - HLA-E/β2 microglobulin - by tumor cells in CRC was associated with an unfavorable prognosis, suggesting its involvement in immune escape. However, the specific receptor of HLA-E/β2m - CD94/NKG2A, inhibitory or CD94/NKG2C, activating - expressed by tumor-infiltrating lymphocytes (TIL), as well as the influence of the microsatellite status in HLA-E/β2m overexpression, remain unknown. Methods: We investigated in the primary tumor of 245 CRC patients 1) the association of HLA-E/β2m overexpression and the density of CD94+ intraepithelial TIL (IEL-TIL) with the microsatellite status, 2) the nature of CD94+ TIL and the receptor expressed - CD94/NKG2A or CD94/NKG2C - and 3) the prognostic influence of CD94+ IEL-TIL. Results: HLA-E/β2m was preferentially overexpressed in MSI compared with MSS CRC (44,6 % vs 18,4 % respectively, p = 0.0001), and significantly associated with a high density of CD94+ IEL-TIL in MSI (0,9% in HLA-E/β2m+ vs 0,2% in HLA-E/β2m– CRC, p = 0,001), and in MSS CRC (0,38% vs 0,15%, p < 0,0001). These CD94+ TIL mostly corresponded to CD8+ αβ T cells preferentially expressing the inhibitory NKG2A chain. Finally, a high density of CD94+ IEL-TIL was independently associated with a worse OS (p = 0.03). Conclusions: These results strongly suggest that HLA-E/β2m - CD94/NKG2A interactions, preferentially up-regulated in MSI CRC, represent a promising inhibitory immune checkpoint. From a clinical point of view, this inhibitory immune checkpoint could be blocked by the new anti-NKG2A monoclonal antibody