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Current Opinion in Otolaryngology &... Feb 2024The purpose of this review is to summarize current evidence regarding the use of induction chemotherapy for a variety of histopathologies of sinonasal malignancy (SNMs)... (Review)
Review
PURPOSE OF REVIEW
The purpose of this review is to summarize current evidence regarding the use of induction chemotherapy for a variety of histopathologies of sinonasal malignancy (SNMs) and to review the potential adverse effects of cytotoxic agents.
RECENT FINDINGS
Historically, patients with locally advanced SNMs have had relatively poor prognoses and high morbidity from treatment. The available retrospective data suggests that induction chemotherapy may improve outcomes for patients with sinonasal undifferentiated carcinoma (SNUC), neuroendocrine carcinoma, squamous cell carcinoma (SSCC), and esthesioneuroblastoma. For SNUC and SSCC, response or nonresponse to induction chemotherapy may prognosticate outcomes and for SNUC specifically, drive selection of definitive therapy. In chemosensitive pathologies, induction chemotherapy appears to improve organ preservation.
SUMMARY
Induction chemotherapy may improve functional and oncologic outcomes for patients with SNMs. Because of the rarity of these pathologies, the available data is primarily retrospective. Future randomized, prospective studies should be performed to further optimize and elucidate the role of induction chemotherapy for SNMs.
Topics: Humans; Retrospective Studies; Prospective Studies; Maxillary Sinus Neoplasms; Carcinoma, Neuroendocrine; Carcinoma, Squamous Cell
PubMed: 38116847
DOI: 10.1097/MOO.0000000000000951 -
Histopathology Jan 2024Currently, lung cancer is treated by the highest number of therapeutic options and the benefits are based on multiple large-scale sequencing studies, translational... (Review)
Review
Currently, lung cancer is treated by the highest number of therapeutic options and the benefits are based on multiple large-scale sequencing studies, translational research and new drug development, which has promoted our understanding of the molecular pathology of lung cancer. According to the driver alterations, different characteristics have been revealed, such as differences in ethnic prevalence, median age and alteration patterns. Consequently, beyond traditional chemoradiotherapy, molecular-targeted therapy and treatment with immune check-point inhibitors (ICI) also became available major therapeutic options. Interestingly, clinical results suggest that the recently established therapies target distinct lung cancer proportions, particularly between the EGFR/ALK and PD-1/PD-L1-positive subsets, e.g. the kinase inhibitors target driver mutation-positive tumours, whereas driver mutation-negative tumours respond to ICI treatment. These therapeutic efficacy-related differences might be explained by the molecular pathogenesis of lung cancer. Addictive driver mutations promote tumour formation with powerful transformation performance, resulting in a low tumour mutation burden, reduced immune surveillance, and subsequent poor response to ICIs. In contrast, regular tobacco smoke exposure repeatedly injures the proximal airway epithelium, leading to accumulated genetic alterations. In the latter pathway, overgrowth due to alteration and immunological exclusion against neoantigens is initially balanced. However, tumours could be generated from certain clones that outcompete immunological exclusion and outgrow the others. Consequently, this cancer type responds to immune check-point treatment. These pathogenic differences are explained well by the two-compartment model, focusing upon the anatomical and functional composition of distinct cellular components between the terminal respiratory unit and the air-conducting system.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Pathology, Molecular; Lung Neoplasms; Carcinoma; Mutation; B7-H1 Antigen
PubMed: 37936491
DOI: 10.1111/his.15080 -
Circulation Aug 2023The number of heart transplants performed annually in the United States and worldwide continues to increase, but there has been little change in graft longevity and... (Review)
Review
The number of heart transplants performed annually in the United States and worldwide continues to increase, but there has been little change in graft longevity and patient survival over the past 2 decades. The reference standard for diagnosis of acute cellular and antibody-mediated rejection includes histologic and immunofluorescence evaluation of endomyocardial biopsy samples, despite invasiveness and high interrater variability for grading histologic rejection. Circulating biomarkers and molecular diagnostics have shown substantial predictive value in rejection monitoring, and emerging data support their use in diagnosing other posttransplant complications. The use of genomic (cell-free DNA), transcriptomic (mRNA and microRNA profiling), and proteomic (protein expression quantitation) methodologies in diagnosis of these posttransplant outcomes has been evaluated with varying levels of evidence. In parallel, growing knowledge about the genetically mediated immune response leading to rejection (immunogenetics) has enhanced understanding of antibody-mediated rejection, associated graft dysfunction, and death. Antibodies to donor human leukocyte antigens and the technology available to evaluate these antibodies continues to evolve. This review aims to provide an overview of biomarker and immunologic tests used to diagnose posttransplant complications. This includes a discussion of pediatric heart transplantation and the disparate rates of rejection and death experienced by Black patients receiving a heart transplant. This review describes diagnostic modalities that are available and used after transplant and the landscape of future investigations needed to enhance patient outcomes after heart transplantation.
Topics: Heart Transplantation; Pathology, Molecular; Graft Rejection; Biomarkers; Humans; Cell-Free Nucleic Acids; Gene Expression Profiling; MicroRNAs; Child; Race Factors; Antibodies; HLA Antigens; Genomics
PubMed: 37603604
DOI: 10.1161/CIRCULATIONAHA.123.062847 -
Nature Communications Oct 2023Current diagnosis of glioma types requires combining both histological features and molecular characteristics, which is an expensive and time-consuming procedure....
Current diagnosis of glioma types requires combining both histological features and molecular characteristics, which is an expensive and time-consuming procedure. Determining the tumor types directly from whole-slide images (WSIs) is of great value for glioma diagnosis. This study presents an integrated diagnosis model for automatic classification of diffuse gliomas from annotation-free standard WSIs. Our model is developed on a training cohort (n = 1362) and a validation cohort (n = 340), and tested on an internal testing cohort (n = 289) and two external cohorts (n = 305 and 328, respectively). The model can learn imaging features containing both pathological morphology and underlying biological clues to achieve the integrated diagnosis. Our model achieves high performance with area under receiver operator curve all above 0.90 in classifying major tumor types, in identifying tumor grades within type, and especially in distinguishing tumor genotypes with shared histological features. This integrated diagnosis model has the potential to be used in clinical scenarios for automated and unbiased classification of adult-type diffuse gliomas.
Topics: Adult; Humans; Brain Neoplasms; Deep Learning; Neuropathology; Glioma
PubMed: 37821431
DOI: 10.1038/s41467-023-41195-9 -
Alzheimer's & Dementia : the Journal of... Aug 2023This study aimed to assess whether biomarkers related to amyloid, tau, and neurodegeneration can accurately predict Alzheimer's disease (AD) neuropathology at autopsy in...
INTRODUCTION
This study aimed to assess whether biomarkers related to amyloid, tau, and neurodegeneration can accurately predict Alzheimer's disease (AD) neuropathology at autopsy in early and late clinical stages.
METHODS
We included 100 participants who had ante mortem biomarker measurements and underwent post mortem neuropathological examination. Based on ante mortem clinical diagnosis, participants were divided into non-dementia and dementia, as early or late clinical stages.
RESULTS
Amyloid positron emission tomography (PET) and cerebrospinal fluid (CSF) amyloid beta (Aβ)42/phosphorylated tau (p-tau)181 showed excellent performance in differentiating autopsy-confirmed AD and predicting the risk of neuropathological changes in early and late clinical stages. However, CSF Aβ42 performed better in the early clinical stage, while CSF p-tau181, CSF t-tau, and plasma p-tau181 performed better in the late clinical stage.
DISCUSSION
Our findings provide important clinical information that, if using PET, CSF, and plasma biomarkers to detect AD pathology, researchers must consider their differential performances at different clinical stages of AD.
HIGHLIGHTS
Amyloid PET and CSF Aβ42/p-tau181 were the most promising candidate biomarkers for predicting AD pathology. CSF Aβ42 can serve as a candidate predictive biomarker in the early clinical stage of AD. CSF p-tau181, CSF t-tau, and plasma p-tau181 can serve as candidate predictive biomarkers in the late clinical stage of AD. Combining APOE ε4 genotypes can significantly improve the predictive accuracy of AD-related biomarkers for AD pathology.
Topics: Humans; Alzheimer Disease; Amyloid beta-Peptides; Autopsy; tau Proteins; Biomarkers
PubMed: 36840620
DOI: 10.1002/alz.12997 -
Pathologie (Heidelberg, Germany) Dec 2023Primary vitreoretinal lymphoma (PVRL) represents a subtype of intraocular lymphomas, which are a subgroup of malignant lymphomas of the eye. PVRL is considered... (Review)
Review
Primary vitreoretinal lymphoma (PVRL) represents a subtype of intraocular lymphomas, which are a subgroup of malignant lymphomas of the eye. PVRL is considered a special form of primary diffuse large cell lymphoma (DLBCL) of the CNS (central nervous system) (PCNSL) and arises primary or secondary to PCNSL. According to the cell of origin (COO) classification of DLBCL, PVRL largely belongs to the activated B‑cell (ABC) type of DLBCL. Based on a recently established genetic-biological classification of DLBCL, PCNSL and thus also PVRL belong to a group of DLBCL of the MYD88/CD79B-mutated (MCD) or cluster 5 subtype, which often shows extranodal manifestations and MYD88 and CD79A mutations as well as CDKN2A deletions.PVRL diagnostics is often complicated as it represents a classic masquerade syndrome. Due to the usually limited material with often large numbers of reactive lymphocytes and/or degenerative changes in the cells, the results of diagnostic tests are difficult to interpret. Classic diagnostic tests include cytology on vitreous aspirates, immunocytochemistry, and clonality analysis.New insights into the spectrum of genetic alterations of vitreoretinal lymphomas (VRL) confirm the close relationship to PCNSL and could significantly improve pathological diagnosis. Next-generation sequencing panel-based diagnostics allow VRL diagnosis confirmation with little DNA in almost 100% of patients in cases with insufficient cytological evidence or lack of clonality detection. PVRL, as well as secondary vitreoretinal lymphomas after PCNSL or extracerebral DLBCL, have high mutation frequencies in characteristically mutated genes in PCNSL or MCD/cluster 5 type DLBCL. Supporting diagnostics, mutation detection can also be performed on cell-free DNA from the vitreous supernatant.
Topics: Humans; Retinal Neoplasms; Myeloid Differentiation Factor 88; Pathology, Molecular; Vitreous Body; Eye Neoplasms; Lymphoma, Large B-Cell, Diffuse; Central Nervous System Neoplasms
PubMed: 37947807
DOI: 10.1007/s00292-023-01251-z -
Journal of Translational Medicine Nov 2023Idiopathic pulmonary fibrosis (IPF) is the most common idiopathic interstitial lung disease. Clinical models to accurately evaluate the prognosis of IPF are currently...
BACKGROUND
Idiopathic pulmonary fibrosis (IPF) is the most common idiopathic interstitial lung disease. Clinical models to accurately evaluate the prognosis of IPF are currently lacking. This study aimed to construct an easy-to-use and robust prediction model for transplant-free survival (TFS) of IPF based on clinical and radiological information.
METHODS
A multicenter prognostic study was conducted involving 166 IPF patients who were followed up for 3 years. The end point of follow-up was death or lung transplantation. Clinical information, lung function tests, and chest computed tomography (CT) scans were collected. Body composition quantification on CT was performed using 3D Slicer software. Risk factors in blood routine examination-radiology-pulmonary function (BRP) were identified by Cox regression and utilized to construct the "BRP Prognosis Model". The performance of the BRP model and the gender-age-physiology variables (GAP) model was compared using time-ROC curves, calibration curves, and decision curve analysis (DCA). Furthermore, histopathology fibrosis scores in clinical specimens were compared between the different risk stratifications identified by the BRP model. The correlations among body composition, lung function, serum inflammatory factors, and profibrotic factors were analyzed.
RESULTS
Neutrophil percentage > 68.3%, pericardial adipose tissue (PAT) > 94.91 cm, pectoralis muscle radiodensity (PMD) ≤ 36.24 HU, diffusing capacity of the lung for carbon monoxide/alveolar ventilation (DLCO/VA) ≤ 56.03%, and maximum vital capacity (VCmax) < 90.5% were identified as independent risk factors for poor TFS among patients with IPF. We constructed a BRP model, which showed superior accuracy, discrimination, and clinical practicability to the GAP model. Median TFS differed significantly among patients at different risk levels identified by the BRP model (low risk: TFS > 3 years; intermediate risk: TFS = 2-3 years; high risk: TFS ≈ 1 year). Patients with a high-risk stratification according to the BRP model had a higher fibrosis score on histopathology. Additionally, serum proinflammatory markers were positively correlated with visceral fat volume and infiltration.
CONCLUSIONS
In this study, the BRP prognostic model of IPF was successfully constructed and validated. Compared with the commonly used GAP model, the BRP model had better performance and generalization with easily obtainable indicators. The BRP model is suitable for clinical promotion.
Topics: Humans; Idiopathic Pulmonary Fibrosis; Lung; Prognosis; Vital Capacity; Biomarkers; Fibrosis; Retrospective Studies
PubMed: 37951977
DOI: 10.1186/s12967-023-04668-5 -
Turk Patoloji Dergisi 2024This review which aims to examine the recent and current status of pathology education in medical schools, and covers the publications related to undergraduate pathology... (Review)
Review
OBJECTIVE
This review which aims to examine the recent and current status of pathology education in medical schools, and covers the publications related to undergraduate pathology education published between 2010 January and June 2023.
MATERIAL AND METHOD
A search was performed through PubMed, Google Scholar, Semantic Scholar, and Ulakbim search engines for the Science Citation Index, Science Citation Index Expanded, Emerging Sources Citation Index, Directory of Open Access Journals, Scopus, PubMed as well as TR Dizin indexed articles. The findings are categorized into two periods as 2010 January - 2020 April (pre-COVID-19 pandemic) and May 2020 - 2023 June. A total of 24 reviews/editorials/letters to the editor and 63 research articles in the pre-pandemic period and 11 reviews/ editorials/ letters to the editor and 35 research articles between 2020 May and 2023 June are included in the analysis.
RESULTS
Currently, medical education generally depends on core education programs with defined learning objectives and outcomes. Moreover, problem-based, case-based, and team-based interactive learning are being used along with traditional didactic courses. Additionally, digital/ web-based/remote education methods have gained prominence after the COVID-19 pandemic. The virtual or augmented reality and 3D drawing applications are offered as a solution for the autopsy and macroscopy courses. A scarce number of publications are found on measuring and evaluating the effectiveness of learning.
CONCLUSION
Artificial intelligence in pathology education is a topic that looks likely to become important in the near future. National and international comprehensive standardization is a necessity. A joint effort and collective intelligence are needed to achieve the desired goals in undergraduate pathology education.
Topics: Humans; COVID-19; Education, Medical, Undergraduate; Pathology; Pandemics; SARS-CoV-2; Coronavirus Infections; Pneumonia, Viral; Curriculum; Betacoronavirus
PubMed: 38265100
DOI: 10.5146/tjpath.2023.13048 -
The Australian & New Zealand Journal of... Dec 2023In the most severe stage of endometriosis, Stage IV, intestinal involvement is common. The true prevalence of endometriotic disease of the appendix in this population is...
BACKGROUND
In the most severe stage of endometriosis, Stage IV, intestinal involvement is common. The true prevalence of endometriotic disease of the appendix in this population is not well described. A macroscopically normal looking appendix may harbour endometriosis.
AIMS
Our study aims to assess the role of routinely performing appendicectomy in Stage IV endometriosis surgery, and the histopathological prevalence of true appendiceal endometriosis in this population.
METHODS
This is a retrospective study of women undergoing surgery for Stage IV endometriosis between 2018 to 2022 in a tertiary public hospital in New South Wales, Australia. Patient demographics, age and post-operative complications were retrospectively retrieved from hospital medical records. Inclusion criteria were women with Stage IV endometriosis who underwent routine appendicectomy as part of their endometriosis surgery. Exclusion criteria were women who did not have Stage IV endometriosis, those who had cancer surgery or emergency surgery for endometriosis. The primary outcome of this study was to determine the incidence of appendiceal endometriosis. Secondary outcomes included post-operative complications and length of stay.
RESULTS
Sixty-seven patients were included. The mean age was 36 years. All patients also underwent bowel resection for colorectal endometriosis. There were 35.8% who had confirmed appendiceal endometriosis on histopathology. Post-operative complications included port site infections, colitis, urinary tract infection and ureteric injury. There were no complications related to appendicectomy. Mean length of stay was 4.4 days.
CONCLUSION
Laparoscopic appendicectomy can be safely performed at time of laparoscopic surgical excision of Stage IV endometriosis and should be routinely considered in a subset of Stage IV endometriosis patients with colorectal involvement undergoing surgery.
Topics: Humans; Female; Adult; Male; Appendix; Endometriosis; Retrospective Studies; Appendectomy; Laparoscopy; Postoperative Complications; Colorectal Neoplasms; Treatment Outcome
PubMed: 37427888
DOI: 10.1111/ajo.13730