Atlas of Ex Vivo Prostate Tissue and Cancer Images Using Confocal Laser Endomicroscopy: A Project for Intraoperative Positive Surgical Margin Detection During Radical Prostatectomy.

BACKGROUND: Confocal laser endomicroscopy (CLE) is an optical device that aims to image histological architecture and may be used to reduce positive surgical margins. The ability of CLE to describe prostatic and periprostatic tissues, and prostate cancer (PCa) is still an object of investigation. OBJECTIVE: To create an atlas of ex vivo CLE images of prostatic and periprostatic tissues, and PCa in order to recognise different prostatic structures. DESIGN, SETTING, AND PARTICIPANTS: From November 2017 to February 2018, 15 patients underwent radical prostatectomy for biopsy-proven PCa. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Based on preoperative data and macroscopic examination, tumour location was assessed and confirmed on frozen sections. Prior to ex vivo CLE analysis, prostates were stained with fluorescein 10%. We used a GastroFlex probe to collect images of periprostatic tissue (adipose tissue, fibrous and connective tissues, vessels, nerve sheets, seminal vesicles, and urethra). Normal prostatic glands and tumour tissue according to the Gleason grade were analysed. Each PCa Gleason score was represented. RESULTS AND LIMITATIONS: A total of 139 video clips and 237 pictures of prostatic and periprostatic tissues were collected. Among them, we selected 16 highly representative images. Adipose tissue, fibrous tissue, and connective tissue were supposable in all 15 specimens. PCa glands captured fluorescein in their cytoplasm, normal prostatic glands did not capture fluorescein, and glandular structures were easily recognisable. The principal limitation of this study is its ex vivo nature of the study. CONCLUSIONS: Each CLE image was correlated with the corresponding haematoxylin/eosin/saffron definitive pathology image, allowing building of an atlas as a necessary tool to assess the diagnostic performance of CLE during radical prostatectomy in achieving negative surgical margins. PATIENT SUMMARY: In this study, we aim to provide an atlas of images illustrating prostatic, periprostatic, and PCa tissues obtained using Cellvizio confocal laser endomicroscopy as a tool for further interpretation of intraoperative surgical margins during radical prostatectomy.

Clinical and histological evolution after de novo donor-specific anti-human leukocyte antigen antibodies: a single centre retrospective study.

BACKGROUND: Donor-specific anti-human leukocyte antigen (HLA) antibodies (DSA) can be preformed or de novo (dn). Strategies to manage preformed DSA are well described, but data on the management and outcomes of dnDSA are lacking. METHODS: We performed a retrospective analysis of data from a single centre of the management and outcomes of 22 patients in whom a dnDSA was identified with contemporary and follow up biopsies. RESULTS: Evolution from baseline to follow up revealed a statistically significant loss of kidney function (estimated glomerular filtration rate: 45.9 ± 16.7 versus 37.4 ± 13.8 ml/min/1.73 m2; p = 0.005) and increase in the proportion of patients with transplant glomerulopathy (percentage with cg lesion ≥1: 27.2% vs. 45.4%; p = 0.04). Nine patients were not treated at the time of dnDSA identification, and 13 patients received various drug combinations (e.g., corticosteroids, plasmapheresis, thymoglobulins and/or rituximab). No significant pathological changes were observed for the various treatment combinations. CONCLUSION: Our retrospective analysis of a small sample suggests that dnDSA should be considered a risk factor for the loss of kidney function independent of the baseline biopsy, and multidisciplinary evaluations of the transplant patient are a necessary requirement. Further confirmation in a multicentre prospective trial is required.

Jejunal Occlusion Caused by Heterotopic Gastric and Duodenal Mucosa: A Late Complication of a Complex Intestinal Malformation.

We report a rare case of late complication of a complex intestinal malformation. At day 1 of life, a baby girl underwent resection of an atretic jejunal segment, associated with an enteric duplication harboring foci of gastric and duodenal heterotopia. After an asymptomatic period of 19 years, the patient presented with acute bowel obstruction. Recurrence of the jejunal occlusion at the previous anastomotic site was caused by mucosa hyperplasia in association with heterotopic gastric and duodenal tissue. A Wnt/ß-catenin pathway deregulation was hypothesized but not confirmed by CTNNB1 exon 3 mutation analysis. This case illustrates a rare association of 3 pathologies-namely, intestinal atresia, enteric duplication, and heterotopia, with a late-occurring acute complication.

Phosphocalcic Markers and Calcification Propensity for Assessment of Interstitial Fibrosis and Vascular Lesions in Kidney Allograft Recipients.

Renal interstitial fibrosis and arterial lesions predict loss of function in chronic kidney disease. Noninvasive estimation of interstitial fibrosis and vascular lesions is currently not available. The aim of the study was to determine whether phosphocalcic markers are associated with, and can predict, renal chronic histological changes. We included 129 kidney allograft recipients with an available transplant biopsy in a retrospective study. We analyzed the associations and predictive values of phosphocalcic markers and serum calcification propensity (T50) for chronic histological changes (interstitial fibrosis and vascular lesions). PTH, T50 and vitamin D levels were independently associated to interstitial fibrosis. PTH elevation was associated with increasing interstitial fibrosis severity (r = 0.29, p = 0.001), while T50 and vitamin D were protective (r = -0.20, p = 0.025 and r = -0.23, p = 0.009 respectively). On the contrary, fibroblast growth factor 23 (FGF23) and Klotho correlated only modestly with interstitial fibrosis (p = 0.045) whereas calcium and phosphate did not. PTH, vitamin D and T50 were predictors of extensive fibrosis (AUC: 0.73, 0.72 and 0.68 respectively), but did not add to renal function prediction. PTH, FGF23 and T50 were modestly predictive of low fibrosis (AUC: 0.63, 0.63 and 0.61) but did not add to renal function prediction. T50 decreased with increasing arterial lesions (r = -0.21, p = 0.038). The discriminative performance of T50 in predicting significant vascular lesions was modest (AUC 0.61). In summary, we demonstrated that PTH, vitamin D and T50 are associated to interstitial fibrosis and vascular lesions in kidney allograft recipients independently of renal function. Despite these associations, mineral metabolism indices do not show superiority or additive value to fibrosis prediction by eGFR and proteinuria in kidney allograft recipients, except for vascular lesions where T50 could be of relevance.

The Expression of the Zonula Adhaerens Protein PLEKHA7 Is Strongly Decreased in High Grade Ductal and Lobular Breast Carcinomas.

PLEKHA7 is a junctional protein, which participates in a complex that stabilizes E-cadherin at the zonula adhaerens. Since E-cadherin is involved in epithelial morphogenesis, signaling, and tumor progression, we explored PLEKHA7 expression in cancer. PLEKHA7 expression was assessed in invasive ductal and lobular carcinomas of the breast by immunohistochemistry, immunofluorescence and quantitative RT-PCR. PLEKHA7 was detected at epithelial junctions of normal mammary ducts and lobules, and of tubular and micropapillary structures within G1 and G2 ductal carcinomas. At these junctions, the localization of PLEKHA7 was along the circumferential belt (zonula adhaerens), and only partially overlapping with that of E-cadherin, p120ctn and ZO-1, as shown previously in rodent tissues. PLEKHA7 immunolabeling was strongly decreased in G3 ductal carcinomas and undetectable in lobular carcinomas. PLEKHA7 mRNA was detected in both ductal and lobular carcinomas, with no observed correlation between mRNA levels and tumor type or grade. In summary, PLEKHA7 is a junctional marker of epithelial cells within tubular structures both in normal breast tissue and ductal carcinomas, and since PLEKHA7 protein but not mRNA expression is strongly decreased or lost in high grade ductal carcinomas and in lobular carcinomas, loss of PLEKHA7 is a newly characterized feature of these carcinomas.