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BMJ Case Reports Jun 2024Extranodal involvement in diffuse large B-cell lymphoma (DLBCL) is defined as disease outside of the lymph nodes and occurs in up to one-third of patients, though...
Extranodal involvement in diffuse large B-cell lymphoma (DLBCL) is defined as disease outside of the lymph nodes and occurs in up to one-third of patients, though multiorgan extranodal involvement is rare. Here, we describe a case of a patient presenting with widely metastatic lesions, including involvement of the lung, parotid gland, breast, pancreas, femur and multiple soft tissue masses, with initial concern for primary breast malignancy. Breast pathology and imaging were consistent with triple-expressor, double-hit stage IV high-grade B-cell lymphoma with extensive extranodal involvement. Extranodal involvement is a poor prognostic factor associated with high rates of treatment failure, and novel therapies targeting CD19 are currently being studied for relapsed and refractory DLBCL. Extranodal disease is a complex entity that can involve virtually any organ system and should be considered for new presentations of malignancy.
Topics: Humans; Lymphoma, Large B-Cell, Diffuse; Female; Middle Aged; Breast Neoplasms; Lung Neoplasms; Parotid Neoplasms; Pancreatic Neoplasms; Antineoplastic Combined Chemotherapy Protocols; Fatal Outcome
PubMed: 38945554
DOI: 10.1136/bcr-2023-257416 -
Journal of Gastrointestinal and Liver... Jun 2024
Topics: Humans; Pancreatic Ducts; Cholangiopancreatography, Endoscopic Retrograde; Catheterization; Ampulla of Vater; Treatment Outcome; Male; Female
PubMed: 38944861
DOI: 10.15403/jgld-5386 -
Cancer Cytopathology Jun 2024The World Health Organization (WHO) classification system revised the Papanicolaou Society of Cytopathology (PSC) system for reporting pancreaticobiliary cytopathology....
BACKGROUND
The World Health Organization (WHO) classification system revised the Papanicolaou Society of Cytopathology (PSC) system for reporting pancreaticobiliary cytopathology. To better stratify intraductal and/or cystic neoplasms by cytologic grade, the neoplastic, other category was replaced by two new categories: pancreaticobiliary neoplasm, low-risk/grade (PaN-Low) and pancreaticobiliary neoplasm, high-risk/grade (PaN-High). Low-grade malignancies were placed in the malignant category, and benign neoplasms were placed in the benign/negative for malignancy category.
METHODS
An institutional pathology database search identified patients who underwent endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for pancreatic lesions from January 2015 to April 2022. The absolute risk of malignancy (ROM) was determined by histologic and/or clinical follow-up of at least 6 months, and overall survival rates were calculated across diagnostic categories, comparing the WHO and PSC systems.
RESULTS
In total, 1012 cases were reviewed and recategorized. The ROM for the WHO system was 8.3% for insufficient/inadequate/nondiagnostic, 3.2% for benign/negative for malignancy, 24.6% for atypical, 9.1% for PaN-Low, 46.7% for PaN-High, 75% for suspicious for malignancy, and 100% for malignant. Comparatively, the ROM for the PSC system was 7.4% for nondiagnostic, 3.0% for negative for malignancy, 23.1% for atypical, 0% for neoplastic, benign, 7.3% for neoplastic, other, 75% for suspicious for malignancy, and 100% for malignant. The WHO system demonstrated superior stratification for overall survival.
CONCLUSIONS
The WHO system significantly improves the stratification of ROM and overall survival across diagnostic categories by introducing the PaN-Low and PaN-High categories and reassigning low-grade malignancies to the malignant category. Analyzing EUS-FNA samples with the WHO system provides critical insights for guiding clinical management.
PubMed: 38944695
DOI: 10.1002/cncy.22880 -
Academic Radiology Jun 2024Pancreas segmentation accuracy at CT is critical for the identification of pancreatic pathologies and is essential for the development of imaging biomarkers. Our...
RATIONALE AND OBJECTIVES
Pancreas segmentation accuracy at CT is critical for the identification of pancreatic pathologies and is essential for the development of imaging biomarkers. Our objective was to benchmark the performance of five high-performing pancreas segmentation models across multiple metrics stratified by scan and patient/pancreatic characteristics that may affect segmentation performance.
MATERIALS AND METHODS
In this retrospective study, PubMed and ArXiv searches were conducted to identify pancreas segmentation models which were then evaluated on a set of annotated imaging datasets. Results (Dice score, Hausdorff distance [HD], average surface distance [ASD]) were stratified by contrast status and quartiles of peri-pancreatic attenuation (5 mm region around pancreas). Multivariate regression was performed to identify imaging characteristics and biomarkers (n = 9) that were significantly associated with Dice score.
RESULTS
Five pancreas segmentation models were identified: Abdomen Atlas [AAUNet, AASwin, trained on 8448 scans], TotalSegmentator [TS, 1204 scans], nnUNetv1 [MSD-nnUNet, 282 scans], and a U-Net based model for predicting diabetes [DM-UNet, 427 scans]. These were evaluated on 352 CT scans (30 females, 25 males, 297 sex unknown; age 58 ± 7 years [ ± 1 SD], 327 age unknown) from 2000-2023. Overall, TS, AAUNet, and AASwin were the best performers, Dice= 80 ± 11%, 79 ± 16%, and 77 ± 18%, respectively (pairwise Sidak test not-significantly different). AASwin and MSD-nnUNet performed worse (for all metrics) on non-contrast scans (vs contrast, P < .001). The worst performer was DM-UNet (Dice=67 ± 16%). All algorithms except TS showed lower Dice scores with increasing peri-pancreatic attenuation (P < .01). Multivariate regression showed non-contrast scans, (P < .001; MSD-nnUNet), smaller pancreatic length (P = .005, MSD-nnUNet), and height (P = .003, DM-UNet) were associated with lower Dice scores.
CONCLUSION
The convolutional neural network-based models trained on a diverse set of scans performed best (TS, AAUnet, and AASwin). TS performed equivalently to AAUnet and AASwin with only 13% of the training set size (8488 vs 1204 scans). Though trained on the same dataset, a transformer network (AASwin) had poorer performance on non-contrast scans whereas its convolutional network counterpart (AAUNet) did not. This study highlights how aggregate assessment metrics of pancreatic segmentation algorithms seen in other literature are not enough to capture differential performance across common patient and scanning characteristics in clinical populations.
PubMed: 38944630
DOI: 10.1016/j.acra.2024.06.015 -
The Surgical Clinics of North America Aug 2024Pancreatic neuroendocrine tumors (PNETs) arise from neuroendocrine cells and are a rare class of heterogenous tumors with increasing incidence. The diagnosis, staging,... (Review)
Review
Pancreatic neuroendocrine tumors (PNETs) arise from neuroendocrine cells and are a rare class of heterogenous tumors with increasing incidence. The diagnosis, staging, treatment, and prognosis of PNETs depend heavily on identifying the histologic features and biological mechanisms. Here, the authors provide an overview of the diagnostic workup (biomarkers and imaging), grade, and staging of PNETs. The authors also explore associated genetic mutations and molecular pathways and describe updated guidelines on surgical and systemic treatment modalities.
Topics: Humans; Pancreatic Neoplasms; Neuroendocrine Tumors; Neoplasm Staging; Pancreatectomy; Prognosis
PubMed: 38944507
DOI: 10.1016/j.suc.2024.02.019 -
Journal of the American Chemical Society Jun 2024Ascorbic acid (AA) has been attracting great attention with its emerging potential in T cell-dependent antitumor immunity. However, premature blood clearance and...
Ascorbic acid (AA) has been attracting great attention with its emerging potential in T cell-dependent antitumor immunity. However, premature blood clearance and immunologically "cold" tumors severely compromise its immunotherapeutic outcomes. As such, the reversal of the immunosuppressive tumor microenvironment (TME) has been the premise for improving the effectiveness of AA-based immunotherapy, which hinges upon advanced AA delivery and amplified immune-activating strategies. Herein, a novel coli ( ) outer membrane vesicle (OMV)-red blood cell (RBC) hybrid membrane (ERm)-camouflaged immunomodulatory nanoturret is meticulously designed based on gating of an AA-immobilized metal-organic framework (MOF) onto bortezomib (BTZ)-loaded magnesium-doped mesoporous silica (MMS) nanovehicles, which can realize immune landscape remodeling by chemotherapy-assisted ascorbate-mediated immunotherapy (CAMIT). Once reaching the acidic TME, the acidity-sensitive MOF gatekeeper and MMS core within the nanoturret undergo stepwise degradation, allowing for tumor-selective sequential release of AA and BTZ. The released BTZ can evoke robust immunogenic cell death (ICD), synergistically promote dendritic cell (DC) maturation in combination with OMV, and ultimately increase T cell tumor infiltration together with Mg. The army of T cells is further activated by AA, exhibiting remarkable antitumor and antimetastasis performance. Moreover, the CD8-deficient mice model discloses the T cell-dependent immune mechanism of the AA-based CAMIT strategy. In addition to providing a multifunctional biomimetic hybrid nanovehicle, this study is also anticipated to establish a new immunomodulatory fortification strategy based on the multicomponent-driven nanoturret for highly efficient T cell-activation-enhanced synergistic AA immunotherapy.
PubMed: 38943624
DOI: 10.1021/jacs.4c04840 -
Environmental Pollution (Barking, Essex... Jun 2024Mercuric chloride (HgCl) is a widespread inorganic mercury with digestive toxicity. The pancreas is an important digestive organ in animals, and pancreatic fibrosis (PF)...
Mercuric chloride (HgCl) is a widespread inorganic mercury with digestive toxicity. The pancreas is an important digestive organ in animals, and pancreatic fibrosis (PF) is a major pathological feature of chronic pancreatitis, which can be caused by heavy metals. Selenium (Se) is an essential trace element for the animal organism, performing biological functions in the form of selenoproteins, as well as alleviating the toxicity of heavy metals. In this study, we explored the specific mechanisms underlying the protective effect of Se on HgCl-induced pancreatic injury in chickens. Morphological observation and serum biochemical analysis showed that Se attenuated HgCl-caused pancreatic tissue damage and elevated glucose concentration and α-amylase activity. Next, the expression of oxidative stress indicators such as MDA and GSH-Px as well as inflammation-related markers including IL-1β, IL-6, and TNF-α were detected. Results showed that Se had an inhibitory effect on HgCl-induced oxidative stress and inflammation. Furthermore, we found that Se alleviated HgCl-induced PF by detecting the expression of markers related to PF including TGF-β1, α-SMA, COL1A1, and FN1. Mechanistically, Se attenuated HgCl-induced PF via the MAPK signaling pathway. Importantly, several selenoproteins, especially those with antioxidant activity, were involved in the protective effect of Se on HgCl toxicity. In conclusion, our findings demonstrated that Se inhibited HgCl-induced oxidative stress and inflammation and alleviated chicken PF through the MAPK signaling pathway, in which some antioxidant selenoproteins were involved.
PubMed: 38942272
DOI: 10.1016/j.envpol.2024.124448 -
Stem Cell Reports Jun 2024Genetic differences between pluripotent stem cell lines cause variable activity of extracellular signaling pathways, limiting reproducibility of directed differentiation...
Genetic differences between pluripotent stem cell lines cause variable activity of extracellular signaling pathways, limiting reproducibility of directed differentiation protocols. Here we used human embryonic stem cells (hESCs) to interrogate how exogenous factors modulate endogenous signaling events during specification of foregut endoderm lineages. We find that transforming growth factor β1 (TGF-β1) activates a putative human OTX2/LHX1 gene regulatory network which promotes anterior fate by antagonizing endogenous Wnt signaling. In contrast to Porcupine inhibition, TGF-β1 effects cannot be reversed by exogenous Wnt ligands, suggesting that induction of SHISA proteins and intracellular accumulation of Fzd receptors render TGF-β1-treated cells refractory to Wnt signaling. Subsequently, TGF-β1-mediated inhibition of BMP and Wnt signaling suppresses liver fate and promotes pancreas fate. Furthermore, combined TGF-β1 treatment and Wnt inhibition during pancreatic specification reproducibly and robustly enhance INSULIN cell yield across hESC lines. This modification of widely used differentiation protocols will enhance pancreatic β cell yield for cell-based therapeutic applications.
PubMed: 38942030
DOI: 10.1016/j.stemcr.2024.05.010 -
Artificial Intelligence in Medicine Jun 2024Pancreatic cancer does not show specific symptoms, which makes the diagnosis of early stages difficult with established image-based screening methods and therefore has...
Pancreatic cancer does not show specific symptoms, which makes the diagnosis of early stages difficult with established image-based screening methods and therefore has the worst prognosis among all cancers. Although endoscopic ultrasonography (EUS) has a key role in diagnostic algorithms for pancreatic diseases, B-mode imaging of the pancreas can be affected by confounders such as chronic pancreatitis, which can make both pancreatic lesion segmentation and classification laborious and highly specialized. To address these challenges, this work proposes a semi-supervised multi-task network (SSM-Net) to leverage unlabeled and labeled EUS images for joint pancreatic lesion classification and segmentation. Specifically, we first devise a saliency-aware representation learning module (SRLM) on a large number of unlabeled images to train a feature extraction encoder network for labeled images by computing a contrastive loss with a semantic saliency map, which is obtained by our spectral residual module (SRM). Moreover, for labeled EUS images, we devise channel attention blocks (CABs) to refine the features extracted from the pre-trained encoder on unlabeled images for segmenting lesions, and then devise a merged global attention module (MGAM) and a feature similarity loss (FSL) for obtaining a lesion classification result. We collect a large-scale EUS-based pancreas image dataset (LS-EUSPI) consisting of 9,555 pathologically proven labeled EUS images (499 patients from four categories) and 15,500 unlabeled EUS images. Experimental results on the LS-EUSPI dataset and a public thyroid gland lesion dataset show that our SSM-Net clearly outperforms state-of-the-art methods.
PubMed: 38941908
DOI: 10.1016/j.artmed.2024.102919 -
Cancer Epidemiology Jun 2024Data on social inequalities in cancer mortality are sparse, especially in low- and middle-income countries. We aimed to analyze the socioeconomic inequalities in cancer...
INTRODUCTION
Data on social inequalities in cancer mortality are sparse, especially in low- and middle-income countries. We aimed to analyze the socioeconomic inequalities in cancer mortality in Costa Rica between 2010 and 2018.
METHODS
We linked 9-years of data from the National Electoral Rolls, National Birth Index and National Death Index to classify deaths due to cancer and socioeconomic characteristics of the district of residence, as measured by levels of urbanicity and wealth. We analyzed the fifteen most frequent cancer sites in Costa Rica among the 2.7 million inhabitants aged 20 years and older. We used a parametric survival model based on a Gompertz distribution.
RESULTS
Compared to urban areas, mixed and rural area residents had lower mortality from pancreas, lung, breast, prostate, kidney, and bladder cancers, and higher mortality from stomach cancer. Mortality from stomach, lung and cervical cancer was higher, and mortality from colorectal cancer, non-Hodgkin lymphoma and leukemia was lower in the most disadvantaged districts, compared to the wealthiest ones.
CONCLUSION
We observed marked disparities in cancer mortality in Costa Rica in particular from infection- and lifestyle- related cancers. There are important opportunities to reduce disparities in cancer mortality by targeting cancer prevention, early detection and opportune treatment, mainly in urban and disadvantaged districts.
PubMed: 38941875
DOI: 10.1016/j.canep.2024.102604