Long-Term Follow-Up of Cadaveric Breast Augmentation: What Can We Learn?

Breast augmentation with cadaveric fat graft has long been available to patients in Eastern European countries, primarily in the Soviet Union and Eastern Germany. Most such procedures were performed from the 1970s to the 1990s. Although only a few case reports have been published, all of which involved complications that appeared several years after the procedure, it appears that, surprisingly, this nonvascularized and incompatible immunologic tissue is relatively well tolerated. We present the case of a 45-year-old Russian woman who underwent breast explantation, due to breast hardness and pain, 15 years after breast augmentation with cadaveric fat grafting. Through genetic studies, we confirmed that the host and the graft were HLA incompatible. Moreover, results of analyses excluded the possibility of an acute or chronic immunologic rejection by the host. We suppose that the early complications that often occur in such cases might result from a nonspecific, inflammatory reaction induced by acute tissue ischemia and necrosis, and the late local complications that occur years later may relate more to chronic inflammation, due to nonvascularized tissue, than to immunologic rejection. Therefore, we propose that different mechanisms may explain how this allogenic fat tissue could have been tolerated by the patient's immune system. We particularly underline the immunomodulatory effect of mesenchymal stem cells, which are abundant in adipose tissues. This characteristic of fat tissue should be investigated further to assess its potential in treating autoimmune diseases or reducing the likelihood of allograft rejections. Level of Evidence 5 Ris

Lymphangiogenesis and tumor metastasis

The lymphatic system transports interstitial fluid and macromolecules from tissues back to the blood circulation, and plays an important role in the immune response by directing the traffic of lymphocytes and antigen-presenting cells. The lymphatic system also constitutes one of the most important pathways of tumor dissemination. In many human cancers, increased expression of vascular endothelial growth factor-C (VEGF-C) is correlated with regional lymph node metastases. Experimental studies using transgenic mice overexpressing VEGF-C or xenotransplantation of VEGF-C-expressing tumor cells into immunodeficient mice have demonstrated a role for VEGF-C in tumor lymphangiogenesis and the subsequent formation of lymph node metastases. However, there is at present little evidence for lymphangiogenesis in human tumors and the relative importance of preexisting vs. newly formed lymphatics for metastasis in humans remains to be determined. Nonetheless, the striking correlation between the levels of VEGF-C in primary human tumors and lymph node metastases predicts its importance in cancer spread. Aside from promoting lymphangiogenesis, VEGF-C may also activate lymphatics to promote tumor cell chemotaxis, lymphatic intravasation and hence tumor cell disseminatio

Experimental noninferiority trial of synthetic small-caliber biodegradable versus stable vascular grafts

ObjectiveLong-term evolution of polycaprolactone vascular prostheses has been investigated recently. The goal of this study was to evidence a noninferiority of such grafts compared with expanded polytetrafluoroethylene (ePTFE) implants in an aortic replacement model in the rat.MethodsFourteen anesthetized Sprague-Dawley rats received an infrarenal aortic graft (biodegradable, n = 8; expanded polytetrafluoroethylene, n = 6) replacement (end to end; inner diameter, 2 mm). Biodegradable grafts (polycaprolactone) were produced by random micro-/nanofiber electrospinning. After a median survival of 16.5 months, in vivo ultrasonography and angiography as well as postexplantation microcomputed tomography, histomorphometry, immunohistochemistry, and scanning electron microscopy were performed.ResultsPatency was 100% for polycaprolactone and 67% for ePTFE. No aneurysmal dilatation or stenoses were found in either group. Compliance was significantly higher for polycaprolactone compared with ePTFE (8.2 ± 1.0%/100 mm Hg vs 5.7 ± 0.7%/100 mm Hg; P < .01), but markedly reduced compared with adjacent native aortas and the control group. Histologically, low cellular in-growth was found in ePTFE whereas polycaprolactone showed significantly greater homogenous cellularity, producing an autologous extracellular matrix (10.8% ± 4.0% vs 32.1% ± 9.2%, P < .0001). Morphometry showed 100% neo-endothelialization for both grafts with a totally confluent endothelial coverage for polycaprolactone grafts by scanning electron microscope. More intimal hyperplasia was found in ePTFE compared with polycaprolactone grafts. Calcification was higher in ePTFE than in polycaprolactone grafts (15.8% vs 7.0%, P = .04) and was absent in controls.ConclusionsOutcomes of synthetic biodegradable nanofiber polycaprolactone grafts are not inferior compared with the clinically used expanded polytetrafluoroethylene grafts after long-term implantation in the rat aorta. Moreover, these implants show better patency, compliance, endothelialization, and cell in-growth, and less intimal hyperplasia and calcification than their counterparts

Knowledge of cytology results affects the performance of colposcopy: a crossover study

peer reviewedAbstract Objective – To determine whether knowledge of cytology affects the colposcopist’s diagnostic accuracy in the identification of cervical intraepithelial neoplasia grade 2 and worse (≥ CIN2). Method – In this cross-over study, healthcare professionals interpreted colposcopy images from 80 patient cases with known histological diagnoses. For each case, 2 images taken with a colposcope were provided (native and after acetic acid application). Inclusion criteria consisted of women with a transformation zone type 1 or 2, who had both a cytological and histological diagnosis. Cases were distributed across two online surveys, one including and one omitting the cytology. A wash-out period of six weeks between surveys was implemented. Colposcopists were asked to give their diagnosis for each case as < CIN2 or ≥ CIN2 on both assessments. Statistical analysis was conducted to compare the two interpretations. Results – Knowledge of cytology significantly improved the sensitivity when interpreting colposcopic images, from 51.1% [95%CI: 39.3 to 62.8] to 63.7% [95%CI: 52.1 to 73.9] and improved the specificity from 63.5% [95%CI: 52.3 to 73.5] to 76.6% [95%CI: 67.2 to 84.0]. Sensitivity was higher by 38.6% when a high-grade cytology (ASC-H, HSIL, AGC) was communicated compared to a low-grade cytology (inflammation, ASC-US, LSIL). Specificity was higher by 31% when a low-grade cytology was communicated compared to a high-grade. Conclusion – Our data suggests that knowledge of cytology increases sensitivity and specificity for diagnosis of ≥ CIN2 lesions at colposcopy. Association between cytology and histology may have contributed to the findings

Molecular apocrine tumours in EORTC 10994/BIG 1-00 phase III study: pathological response after neoadjuvant chemotherapy and clinical outcomes

Background: We explored, within the EORTC10994 study, the outcomes for patients with molecular apocrine (MA) breast cancer, and defined immunohistochemistry (IHC) as androgen-receptor (AR) positive, oestrogen (ER) and progesterone (PR) negative. We also assessed the concordance between IHC and gene expression arrays (GEA) in the identification of MA cancers. Methods: Centrally assessed biopsies for AR, ER, PR, HER2 and Ki67 by IHC were classified into six subtypes: MA, triple-negative (TN) basal-like, luminal A, luminal B HER2 negative, luminal B HER2 positive and “other”. The two main objectives were the pCR rates and survival outcomes in the overall MA subtype (and further divided by HER2 status) and the remaining five subtypes. Results: IHC subtyping was obtained in 846 eligible patients. Ninety-three (11%) tumours were classified as the MA subtype. Both IHC and GEA data were available for 64 patients. In this subset, IHC concordance was 88.3% in identifying MA tumours compared with GEA. Within the MA subtype, pCR was observed in 33.3% of the patients (95% CI: 29.4–43.9) and the 5-year recurrence-free interval was 59.2% (95% CI: 48.2–68.6). Patients with MA and TN basal-like tumours have lower survival outcomes. Conclusions: Irrespective of their HER2 status, the prognosis for MA tumours remains poor and adjuvant trials evaluating anti-androgens should be considered.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Schwannoma-like pleomorphic adenoma of the parotid

Pleomorphic adenoma is the most common benign salivary gland tumour. It can occur in any salivary gland, but is most frequently found in the parotid gland. Chondroid metaplasia is a frequent finding in pleomorphic adenoma. Other forms of metaplasia have been described, but are encountered less frequently. We report a rare case of unusual pleomorphic adenoma of the parotid gland with schwannoma-like feature

H2AX promotes replication fork degradation and chemosensitivity in BRCA-deficient tumours

Histone H2AX plays a key role in DNA damage signalling in the surrounding regions of DNA double-strand breaks (DSBs). In response to DNA damage, H2AX becomes phosphorylated on serine residue 139 (known as γH2AX), resulting in the recruitment of the DNA repair effectors 53BP1 and BRCA1. Here, by studying resistance to poly(ADP-ribose) polymerase (PARP) inhibitors in BRCA1/2-deficient mammary tumours, we identify a function for γH2AX in orchestrating drug-induced replication fork degradation. Mechanistically, γH2AX-driven replication fork degradation is elicited by suppressing CtIP-mediated fork protection. As a result, H2AX loss restores replication fork stability and increases chemoresistance in BRCA1/2-deficient tumour cells without restoring homology-directed DNA repair, as highlighted by the lack of DNA damage-induced RAD51 foci. Furthermore, in the attempt to discover acquired genetic vulnerabilities, we find that ATM but not ATR inhibition overcomes PARP inhibitor (PARPi) resistance in H2AX-deficient tumours by interfering with CtIP-mediated fork protection. In summary, our results demonstrate a role for H2AX in replication fork biology in BRCA-deficient tumours and establish a function of H2AX separable from its classical role in DNA damage signalling and DSB repair

Third International Consensus Conference on lesions of uncertain malignant potential in the breast (B3 lesions)

The heterogeneous group of B3 lesions in the breast harbors lesions with different malignant potential and progression risk. As several studies about B3 lesions have been published since the last Consensus in 2018, the 3rd International Consensus Conference discussed the six most relevant B3 lesions (atypical ductal hyperplasia (ADH), flat epithelial atypia (FEA), classical lobular neoplasia (LN), radial scar (RS), papillary lesions (PL) without atypia, and phyllodes tumors (PT)) and made recommendations for diagnostic and therapeutic approaches. Following a presentation of current data of each B3 lesion, the international and interdisciplinary panel of 33 specialists and key opinion leaders voted on the recommendations for further management after core-needle biopsy (CNB) and vacuum-assisted biopsy (VAB). In case of B3 lesion diagnosis on CNB, OE was recommended in ADH and PT, whereas in the other B3 lesions, vacuum-assisted excision was considered an equivalent alternative to OE. In ADH, most panelists (76%) recommended an open excision (OE) after diagnosis on VAB, whereas observation after a complete VAB-removal on imaging was accepted by 34%. In LN, the majority of the panel (90%) preferred observation following complete VAB-removal. Results were similar in RS (82%), PL (100%), and FEA (100%). In benign PT, a slim majority (55%) also recommended an observation after a complete VAB-removal. VAB with subsequent active surveillance can replace an open surgical intervention for most B3 lesions (RS, FEA, PL, PT, and LN). Compared to previous recommendations, there is an increasing trend to a de-escalating strategy in classical LN. Due to the higher risk of upgrade into malignancy, OE remains the preferred approach after the diagnosis of ADH

Le rôle des récepteurs à VEGF dans la régulation de l'angiogenèse

L'angiogenèse, c'est-à-dire la formation de nouveaux capillaires sanguins à partir des vaisseaux pré-existants, est essentielle pendant l'embryogenèse. Elle joue un rôle important chez l'adulte normal et également dans diverses pathologies telles que la croissance tumorale et les malformations vasculaires. L'angiogenèse implique la migration et la différenciation de cellules endothéliales, de péricytes et de cellules musculaires lisses. J'ai étudié le rôle de VEGFR-1, -2 et -3 dans l'angiogenèse induite par VEGF-A, VEGF-C, et FGF-2. J'ai cherché à savoir si dans un modèle d'angiogenèse "in vitro", l'invasion induite par VEGF-A ou FGF-2 était modulée par la présence de cellules mésenchymateuses pluripotentes pouvant se différencier en cellules musculaires lisses. Finalement, j'ai décrit une famille présentant une malformation vasculaire appelée angiome en touffe, qui est transmise de manière autosomale dominante. J'ai caractérisé le type de vaisseaux présents dans cette lésion ainsi qu'exclut le lien avec deux gènes