Salomao, Marcela

Abstract Background and Aims Several different types of non-conventional dysplasia have been recently described in inflammatory bowel disease [IBD]. Hypermucinous, goblet cell-deficient and crypt cell dysplasias have received most attention, but there is limited information regarding their clinicopathological features and clinical outcomes. Methods A total of 126 cases of hypermucinous [n = 55], goblet cell-deficient [n = 26] and crypt cell [n = 45] dysplasias from 97 IBD patients were collected from seven different institutions and analysed. Results The cohort included 62 [64%] men and 35 [36%] women with a mean age of 49 years [range: 20–78]. The majority of affected patients had longstanding IBD [mean duration: 18 years]. Nineteen [20%] patients had a concurrent history of primary sclerosing cholangitis. As a group, non-conventional dysplasia was predominantly found in patients with ulcerative colitis [UC] [n = 68; 70%] and occurred in the left colon [n = 80; 63%]; however, hypermucinous dysplasia [57%] was the least frequently associated with UC compared with goblet cell-deficient [74%] and crypt cell [89%] dysplasias [p = 0.016]. Fifty [52%] patients had a history of conventional dysplasia, detected in the same colonic segment as non-conventional dysplasia at a rate of 33%. Goblet cell-deficient dysplasia [74%] was more frequently associated with conventional dysplasia than hypermucinous [43%] and crypt cell [48%] dysplasias [p = 0.044]. While hypermucinous dysplasia often had a polypoid appearance [58%], crypt cell [96%] and goblet cell-deficient [65%] dysplasias were more likely to present as flat/invisible lesions [p < 0.001]. Most lesions were low-grade [87%] at diagnosis, but goblet cell-deficient dysplasia [31%] more often showed high-grade dysplasia [HGD] compared with hypermucinous [15%] and crypt cell [0%] dysplasias [p = 0.003]. Hypermucinous dysplasia usually demonstrated a tubulovillous/villous architecture [76%], whereas goblet cell-deficient dysplasia was predominantly tubular [92%]. A flat architecture was exclusively associated with crypt cell dysplasia [100%] [p < 0.001]. Immunohistochemical stain results for p53 were available for 33 lesions; 14 [42%] showed strong [3+] and patchy [10–50%] to diffuse [>50%] nuclear overexpression or null staining pattern, including four [33%] of 12 hypermucinous, two [29%] of seven goblet cell-deficient and eight [57%] of 14 crypt cell dysplastic lesions [p = 0.726]. Follow-up biopsies or resections were available for 92 low-grade lesions from 71 patients; 55 [60%] lesions, including 19 [49%] of 39 hypermucinous, 10 [59%] of 17 goblet cell-deficient and 26 [72%] of 36 crypt cell dysplastic lesions [p = 0.116], were associated with subsequent detection of HGD [n = 34; 37%] or adenocarcinoma [n = 21; 23%] at the site of previous biopsy or in the same colonic segment within a mean follow-up time of 12 months [range: <1–73]. Conclusions Hypermucinous, goblet cell-deficient and crypt cell dysplasias have distinct clinicopathological features but appear to have a similar high risk of association with advanced neoplasia [HGD or adenocarcinoma]. More than half of the lesions [66%] presented as flat/invisible dysplasia, suggesting that IBD patients may benefit from random biopsy sampling in addition to targeted biopsies. Although not uncommonly associated with conventional dysplasia, non-conventional dysplasia may be the only dysplastic subtype identified in IBD patients. Therefore, it is important to recognize these non-conventional subtypes and recommend complete removal and/or careful examination and follow-up.

Objectives Misplaced epithelium in adenomas can occasionally be difficult to distinguish from invasive adenocarcinoma. We evaluated interobserver variability in the assessment of left-sided colon polypectomies for pseudoinvasion versus invasive adenocarcinoma and further investigated relevant histological findings. Methods 28 consecutive left-sided colon polyps with the keywords “pseudoinvasion”, “epithelial misplacement”, “herniation”, “prolapse” or “invasive adenocarcinoma” were collected from 28 patients and reviewed by eight gastrointestinal pathologists. Participants assessed stromal hemosiderin, lamina propria/eosinophils surrounding glands, desmoplasia, high grade dysplasia/intramucosal adenocarcinoma and margin status and rendered a diagnosis of pseudoinvasion, invasive adenocarcinoma, or both. Results Agreement among pathologists was substantial for desmoplasia (κ=0.70), high grade dysplasia/intramucosal adenocarcinoma (κ=0.66), invasive adenocarcinoma (κ=0.63) and adenocarcinoma at the margin (κ=0.65). There was moderate agreement for hemosiderin in stroma (κ=0.53) and prolapse/pseudoinvasion (κ=0.50). Agreement was low for lamina propria/eosinophils around glands (κ=0.12). For invasive adenocarcinoma, seven or more pathologists agreed in 24 of 28 cases (86%), and there was perfect agreement in 19/28 cases (68%). For pseudoinvasion, seven or more pathologists agreed in 19 of 28 cases (68%), and there was perfect agreement in 16/28 cases (57%). Conclusion Moderate to substantial, though imperfect, agreement was achieved in the distinction of pseudoinvasion from invasive carcinoma.

We present a case of haemorrhagic enterocolitis in a patient with SARS-CoV-2 who recovered from respiratory failure after support with venovenous extracorporeal membrane oxygenation. We describe clinicopathological features consistent with the systemic coinfection/reactivation of cytomegalovirus (CMV) concurrent with COVID-19 infection and the protracted clinical course of resolution of gastrointestinal inflammation after the treatment of CMV infection. Stool PCR, abdominal CT perfusion scan and histological examination of ileal and colonic tissues excluded enterocolitis secondary to other causes of infection (common viral, bacterial and protozoal gastrointestinal pathogens), macrovascular and microvascular ischaemia and classic inflammatory bowel disease, respectively. We propose possible synergistic pathophysiologic mechanisms for enterocolitis complicating severe COVID-19 infection: (1) T lymphocyte depletion and immune response dysregulation, (2) use of immunomodulators in the management of severe COVID-19 infection and (3) high concentration of ACE-2 receptors for COVID-19 virus in the gastrointestinal tract.

AbstractVascular embolization is a life‐saving minimally invasive catheter‐based procedure performed to treat bleeding vessels. Through these catheters, numerous metallic coils are often pushed into the bleeding artery to stop the blood flow. While there are numerous drawbacks to coil embolization, physician expertise, availability of these coils, and their costs further limit their use. Here, a novel blood‐derived embolic material (BEM) with regenerative properties, that can achieve instant and durable intra‐arterial hemostasis regardless of coagulopathy, is developed. In a large animal model of vascular embolization, it is shown that the BEM can be prepared at the point‐of‐care within 26 min using fresh blood, it can be easily delivered using clinical catheters to embolize renal and iliac arteries, and it can achieve rapid hemostasis in acutely injured vessels. In swine arteries, the BEM increases cellular proliferation, angiogenesis, and connective tissue deposition, suggesting vessel healing and durable vessel occlusion. The BEM has significant advantages over embolic materials used today, making it a promising new tool for embolization.

AbstractTranscatheter embolization is a minimally invasive procedure that uses embolic agents to intentionally block diseased or injured blood vessels for therapeutic purposes. Embolic agents in clinical practice are limited by recanalization, risk of non‐target embolization, failure in coagulopathic patients, high cost, and toxicity. Here, a decellularized cardiac extracellular matrix (ECM)‐based nanocomposite hydrogel is developed to provide superior mechanical stability, catheter injectability, retrievability, antibacterial properties, and biological activity to prevent recanalization. The embolic efficacy of the shear‐thinning ECM‐based hydrogel is shown in a porcine survival model of embolization in the iliac artery and the renal artery. The ECM‐based hydrogel promotes arterial vessel wall remodeling and a fibroinflammatory response while undergoing significant biodegradation such that only 25% of the embolic material remains at 14 days. With its unprecedented proregenerative, antibacterial properties coupled with favorable mechanical properties, and its superior performance in anticoagulated blood, the ECM‐based hydrogel has the potential to be a next‐generation biofunctional embolic agent that can successfully treat a wide range of vascular diseases.

Abstract We report a case of an adult male patient with multifocal urinary bladder paragangliomas, which were negative on 68Ga-DOTATATE PET/CT scan, but positive on 123I-MIBG SPECT/CT scan. While the 68Ga-DOTA analog PET/CT exhibits superior performance in diagnosis and staging of pheochromocytoma and paraganglioma, our case demonstrates negative somatostatin receptor expression in this rare entity and indicates that 123I-MIBG SPECT/CT still plays a vital role in characterization of bladder paraganglioma.

Abstract INTRODUCTION The quantification of intratumoral heterogeneity – through radiomics-based approaches - can help resolve the regionally distinct genetic drug targets that may co-exist within a single Glioblastoma (GBM) tumor. While this offers potential diagnostic value under the paradigm of individualized oncology, clinical decision-making must also consider the degree of uncertainty associated with each model. In this study, we evaluate the performance of a novel machine-learning (ML) algorithm, called Gaussian Process (GP) modeling, that can quantify the impact of multiple sources of uncertainty in ML model development and prediction accuracy, including variabilities in the copy number measurement, radiomics features, training sample characteristics, and training sample size. METHOD We collected 95 image-localized biopsies from 25 primary GBM patients. We coregistered stereotactic locations with preoperative multi-parametric MRI features (conventional MRI, DSC perfusion, Diffusion Tensor Imaging) to generate spatially matched pairs of MRI and copy number variants (CNV) for for each biopsy. We developed a Gaussian Process (GP) model to predict CNV for Epidermal Growth Factor Receptor (EGFR) based on MRI radiomic features in each patient. We used leave-one-patient-out cross validation to quantify prediction accuracy and model uncertainty. Spatial prediction and uncertainty (p-value) maps were overlaid to help visualize regional genetic variation of EGFR and uncertainty of the radiomic predictions. RESULT: The initial GP radiomics model for EGFR amplification (CNV > 3.5) produced a sensitivity of 0.8 and specificity of 0.8. Samples/regions associated with high uncertainty (p-value >0.05) correlated with either 1) extrapolation of radiomic features from the training set-defined feature space or 2) insufficient training samples in the feature space. CONCLUSION We present a ML-based model that quantifies spatial genetic heterogeneity in GBM, while also estimating model uncertainties that result from multi-source data variabilities. This approach lays the groundwork for prospective clinical integration of modeling-based diagnostic approaches in the paradigm of individualized medicine.