Effectiveness of immune checkpoint inhibitors in the treatment of kidney cancer oral metastasis. A case report.

Oral cavity metastasis from renal cell carcinoma is rare with poor prognosis. Recently immune checkpoint inhibitors (ICIs) have shown promising outcomes in the treatment of advanced RCC. Herein, we report a case of palatal lesion mimicking vascular tumor in a 60-year-old woman with locally advanced kidney cancer (T3aN0M0). She underwent an excisional biopsy, and histopathological examinations revealed an oral metastasis from clear cell renal cell carcinoma (ccRCC). The patient was treated with a combination of two ICIs with nivolumab, a programmed death 1 (PD-1), and ipilimumab, a cytotoxic T-lymphocyte-associated antigen 4 (CTLA4). After 3 cycles of systemic immunotherapy, the palate was completely well healed and after 13 months of follow-up, there was no evidence of recurrence. Regarding treatments, radical surgery is often recommended due to a high local control in case of solitary lesions or oligo-metastases. However, this option therapy is associated with a poor quality of life. To the best of our knowledge, this is the first case to suggest the benefits of ICIs in the treatment of oral metastases from ccRCC. Combining ICIs with conservative surgery could be another treatment option for oral metastasis in patients with renal cell carcinoma.

[Systemic lupus erythematosus presenting as severe alveolar hypoventilation and the shrinking lung syndrome]. / Hypoventilation alvéolaire sévère révélant un shrinking lung syndrome lupique.

INTRODUCTION: The shrinking lung syndrome (SLS) is a rare complication of systemic lupus erythematosus. CASE REPORT: A 69-year-old man presented with exertional dyspnoea, muscle weakness, and weight loss of 15kg in 6months. Pulmonary function tests revealed a restrictive lung disorder, with a dramatic decrease in maximal inspiratory pressure (17% of theoretical value), and alveolar hypoventilation (pH 7.43; PaCO2 55mmHg). A thoracic CT-scan showed bilateral diaphragmatic elevation. The creatinine phophokinase level was increased at 280U/L. Progress was marked by a rapidly increasing respiratory acidosis (pH 7.24, PaCO2 109mmHg) requiring invasive ventilation. Auto-immune studies revealed positive anti-nuclear antibodies (1/800) and positive anti-native DNA antibody at 45U/L. Treatment with systemic corticosteroids led to an initial improvement but it was not possible to discontinue mechanical ventilation. The outcome was fatal. Autopsy did not reveal any other cause and a diagnosis of the SLS associated with lupus was confirmed. CONCLUSION: The interesting features of this case report consist of: 1) the presentation of the SLS as an alveolar hypoventilation with a fatal outcome, 2) the presentation of systemic lupus as SLS.

Harnessing Wharton's jelly stem cell differentiation into bone-like nodule on calcium phosphate substrate without osteoinductive factors.

An important aim of bone regenerative medicine is to design biomaterials with controlled chemical and topographical features to guide stem cell fate towards osteoblasts without addition of specific osteogenic factors. Herein, we find that sprayed bioactive and biocompatible calcium phosphate substrates (CaP) with controlled topography induce, in a well-orchestrated manner, Wharton's jelly stem cells (WJ-SCs) differentiation into osteoblastic lineage without any osteogenic supplements. The resulting WJ-SCs commitment exhibits features of native bone, through the formation of three-dimensional bone-like nodule with osteocyte-like cells embedded into a mineralized type I collagen. To our knowledge, these results present the first observation of a whole differentiation process from stem cell to osteocytes-like on a synthetic material. This suggests a great potential of sprayed CaP and WJ-SCs in bone tissue engineering. These unique features may facilitate the transition from bench to bedside and the development of successful engineered bone. STATEMENT OF SIGNIFICANCE: Designing materials to direct stem cell fate has a relevant impact on stem cell biology and provides insights facilitating their clinical application in regenerative medicine. Inspired by natural bone compositions, a friendly automated spray-assisted system was used to build calcium phosphate substrate (CaP). Sprayed biomimetic solutions using mild conditions led to the formation of CaP with controlled physical properties, good bioactivity and biocompatibility. Herein, we show that via optimization of physical properties, CaP substrate induce osteogenic differentiation of Wharton's jelly stem cells (WJ-SCs) without adding osteogenic supplement factors. These results suggest a great potential of sprayed CaP and WJ-SCs in bone tissue engineering and may facilitate the transition from bench to beside and the development of clinically successful engineered bone.

Review article: the histological assessment of disease activity in ulcerative colitis.

BACKGROUND: In patients with ulcerative colitis (UC), mucosal healing has emerged as a major therapeutic goal, and is usually assessed endoscopically. Histological healing does not correlate very well with endoscopic mucosal healing in UC and persistent histological inflammation might be a better predictor of future clinical relapse than the endoscopic appearance alone. AIM: To define how histological assessment of disease activity should be best done in UC. METHODS: Electronic (PubMed/Embase) and manual search. RESULTS: At least 18 histological indices to assess disease activity in UC have been described, though none are fully validated. However, histological assessment is increasingly used as a secondary endpoint in clinical trials in UC. After reviewing and discussing existing histological scoring systems for UC activity, we describe features of histological response and define three grades of activity: (i) histological healing - complete resolution of abnormalities; (ii) quiescent disease, - lack of mucosal neutrophils but chronic inflammation may remain; (iii) active disease - presence of neutrophils plus possible epithelial damage. It is recommended that two biopsies are taken from each colonic segment which should include always biopsy of the rectum and the most affected segments. There is to date no agreed preferable scoring system but the Geboes Index is the best validated (kappa for interobserver variation 0.59-0.70). CONCLUSION: Histological assessment of disease activity in UC is increasingly used, but needs to be carefully defined.