Gastric cancer (GC) is the third leading cause of cancer-related death worldwide with a five-year survival rate of around 25%, and 4% when diagnosed at a metastatic stage. Cancer stem cells (CSC) have recently been characterized as being responsible for resistance to radio/chemotherapies and metastasis formation, opening up perspectives for new targeted therapies. Those CSCs express biomarkers such as cluster of differentiation 44 (CD44) and display high aldehyde dehydrogenase activity that converts vitamin A-derived retinal into retinoic acids. All-trans retinoic acid (ATRA), which has pro-differentiating properties, has revolutionized the prognosis of acute promyelotic leukemia by increasing its remission rate from 15% to 85%. Recent studies have started to show that ATRA also has an anti-tumoral role on solid cancers such as GC. The purpose of this review is therefore to summarize the work that evaluated the effects of ATRA in GC and to evaluate whether its anti-cancerous action involves gastric CSCs targeting. It has been demonstrated that ATRA can block the cell cycle, enhance apoptosis, and decrease gastric CSCs properties in GC cell lines, tumorspheres, and patient-derived xenograft mice models. Therefore, retinoids and new synthetic retinoids seem to be a promising step forward in targeted therapy of gastric CSC in combination with existing chemotherapies. Future studies should probably focus on these points.

Gastric cancer is the third leading cause of cancer mortality worldwide. Cancer stem cells (CSC) are at the origin of tumor initiation, chemoresistance, and the formation of metastases. However, there is a lack of mouse models enabling the study of the metastatic process in gastric adenocarcinoma (GC). The aims of this study were to develop original mouse models of patient-derived primary GC orthotopic xenografts (PDOX) allowing the development of distant metastases as preclinical models to study the anti-metastatic efficiency of drugs such as the phosphatidylinositol 3-kinase (PI3K) inhibitor Buparlisib (BKM120). Luciferase-encoding cells generated from primary GC were injected into the stomach wall of immunocompromised mice; gastric tumor and metastases development were followed by bioluminescence imaging. The anti-CSC properties of BKM120 were evaluated on the GC cells’ phenotype (CD44 expression) and tumorigenic properties in vitro and in vivo on BKM120-treated mice. After eight weeks, PDOX mice formed tumors in the stomach as well as distant metastases, that were enriched in CSC, in the liver, the lung, and the peritoneal cavity. BKM120 treatment significantly inhibited the CSC properties in vitro and reduced the number of distant metastases in mice. These new preclinical models offer the opportunity to study the anti-metastatic efficiency of new CSC-based therapeutic strategies.

Background Multiple endocrine neoplasia type 1 (MEN1)‐associated primary hyperparathyroidism (pHPT) is classically associated with an asymmetric and asynchronous parathyroid involvement. Subtotal parathyroidectomy (STP), which is currently the recommended surgical treatment, carries a high risk of permanent hypoparathyroidism. The results of less than subtotal parathyroidectomy (LSTP) are conflicting, and its place in this setting is still a matter of debate. The aim of this study was to identify the place of LSTP in the surgical management of patients with MEN‐associated pHPT. Methods A systematic literature review was conducted in accordance with PRISMA and MOOSE guidelines, for studies comparing STP and LSTP for MEN1‐associated pHPT. The results of the two techniques, regarding permanent hypoparathyroidism, persistent hyperparathyroidism and recurrent hyperparathyroidism were computed using pairwise random‐effect meta‐analysis. Results Twenty‐five studies comparing STP and LSTP qualified for inclusion in the quantitative synthesis. In total, 947 patients with MEN1‐associated pHPT were allocated to STP (n = 569) or LSTP (n = 378). LSTP reduces the risk of permanent hypoparathyroidism [odds ratio (OR) 0.29, confidence interval (CI) 95% 0.17–0.49)], but exposes to higher rates of persistent hyperparathyroidism [OR 4.60, 95% CI 2.66–7.97]. Rates of recurrent hyperparathyroidism were not significantly different between the two groups [OR 1.26, CI 95% 0.83–1.91]. Conclusions LSTP should not be abandoned and should be considered as a suitable surgical option for selected patients with MEN1‐associated pHPT. The increased risk of persistent hyperparathyroidism could improve with the emergence of more efficient preoperative localization imaging techniques and a more adequate patients selection.

Background Cancer stem cells (CSCs) are at the origin of tumour initiation and progression in gastric adenocarcinoma (GC). However, markers of metastasis-initiating cells remain unidentified in GC. In this study, we characterized CD44 variants expressed in GC and evaluated the tumorigenic and metastatic properties of CD44v3+ cells and their clinical significance in GC patients. Methods Using GC cell lines and patient-derived xenografts, we evaluated CD44+ and CD44v3+ GC cells molecular signature and their tumorigenic, chemoresistance, invasive and metastatic properties, and expression in patients-derived tissues. Results CD44v3+ cells, which represented a subpopulation of CD44+ cells, were detected in advanced preneoplastic lesions and presented CSCs chemoresistance and tumorigenic properties in vitro and in vivo. Molecular and functional analyses revealed two subpopulations of gastric CSCs: CD44v3+ CSCs with an epithelial-mesenchymal transition (EMT)-like signature, and CD44+/v3– CSCs with an epithelial-like signature; both were tumorigenic but CD44v3+ cells showed higher invasive and metastatic properties in vivo. CD44v3+ cells detected in the primary tumours of GC patients were associated with a worse prognosis. Conclusion CD44v3 is a marker of a subpopulation of CSCs with metastatic properties in GC. The identification of metastasis-initiating cells in GC represents a major advance for further development of anti-metastatic therapeutic strategies.

Background Dyspnoea in patients with a para-oesophageal hernia (PEH) occurs in 7% to 32% of cases and is very disabling, especially in elderly patients, and its origin is not well defined. The present study aims to assess the impact of PEH repair on dyspnoea and respiratory function. Methods From January 2019 to May 2021, all consecutive patients scheduled for PEH repair presenting with a modified Medical Research Council (mMRC) score ≥ 2 for dyspnoea were included. Before and 2 months after surgery, dyspnoea was assessed by both the dyspnoea visual analogue scale (DVAS) and the mMRC scale, as well as pulmonary function tests (PFTs) by plethysmography. Results All 43 patients that were included had pre- and postoperative dyspnoea assessments and PFTs. Median age was 70 years (range 63–73.5 years), 37 (86%) participants were women, median percentage of the intrathoracic stomach was 59.9% (range 44.2–83.0%), and median length of hospital stay was 3 days (range 3–4 days). After surgery, the DVAS decreased statistically significant (5.6 [4.7–6.7] vs. 3.0 [2.3–4.4], p < 0.001), and 37 (86%) patients had a clinically significant decrease in mMRC score. Absolute forced expiratory volume in one second (FEV1), total lung capacity, and forced vital capacity also statistically significantly increased after surgery by an average of 11.2% (SD 17.9), 5.0% (SD 13.9), and 10.7% (SD 14.6), respectively. Furthermore, from the subgroup analysis, it was identified that patients with a lower preoperative FEV1 were more likely to have improvement in it after surgery. No correlation was found between improvement in dyspnoea and FEV1. There was no correlation between the percentage of intrathoracic stomach and dyspnoea or improvement in PFT parameters. Conclusion PEH repair improves dyspnoea and FEV1 in a statistically significant manner in a population of patients presenting with dyspnoea. Patients with a low preoperative FEV1 are more likely to have improvement in it after surgery.

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