The molecular alterations that occur in cells before cancer is manifest are largely uncharted. Lung carcinoma in situ (CIS) lesions are the pre-invasive precursor to squamous cell carcinoma. Although ...microscopically identical, their future is in equipoise, with half progressing to invasive cancer and half regressing or remaining static. The cellular basis of this clinical observation is unknown. Here, we profile the genomic, transcriptomic, and epigenomic landscape of CIS in a unique patient cohort with longitudinally monitored pre-invasive disease. Predictive modeling identifies which lesions will progress with remarkable accuracy. We identify progression-specific methylation changes on a background of widespread heterogeneity, alongside a strong chromosomal instability signature. We observed mutations and copy number changes characteristic of cancer and chart their emergence, offering a window into early carcinogenesis. We anticipate that this new understanding of cancer precursor biology will improve early detection, reduce overtreatment, and foster preventative therapies targeting early clonal events in lung cancer.
Limited studies on whole slide imaging (WSI) in surgical neuropathology reported a perceived limitation in the recognition of mitoses. This study analyzed and compared the inter- and intra-observer ...concordance for atypical meningioma, using glass slides and WSI. Two neuropathologists and two residents assessed the histopathological features of 35 meningiomas—originally diagnosed as atypical—in a representative glass slide and corresponding WSI. For each histological parameter and final diagnosis, we calculated the inter- and intra-observer concordance in the two viewing modes and the predictive accuracy on recurrence. The concordance rates for atypical meningioma on glass slides and on WSI were 54% and 60% among four observers and 63% and 74% between two neuropathologists. The inter-observer agreement was higher using WSI than with glass slides for all parameters, with the exception of high mitotic index. For all histological features, we found median intra-observer concordance of ≥ 79% and similar predictive accuracy for recurrence between the two viewing modes. The higher concordance for atypical meningioma using WSI than with glass slides and the similar predictive accuracy for recurrence in the two modalities suggest that atypical meningioma may be safely diagnosed using WSI.
the problem in early diagnosis of sporadic cancer is understanding the individual's risk to develop disease. In response to this need, global scientific research is focusing on developing predictive ...models based on non-invasive screening tests. A tentative solution to the problem may be a cancer screening blood-based test able to discover those cell requirements triggering subclinical and clinical onset latency, at the stage when the cell disorder, i.e. atypical epithelial hyperplasia, is still in a subclinical stage of proliferative dysregulation.
a well-established procedure to identify proliferating circulating tumor cells was deployed to measure the cell proliferation of circulating non-haematological cells which may suggest tumor pathology. Moreover, the data collected were processed by a supervised machine learning model to make the prediction.
the developed test combining circulating non-haematological cell proliferation data and artificial intelligence shows 98.8% of accuracy, 100% sensitivity, and 95% specificity.
this proof of concept study demonstrates that integration of innovative non invasive methods and predictive-models can be decisive in assessing the health status of an individual, and achieve cutting-edge results in cancer prevention and management.
Background: Digital pathology has progressed over the last two decades, with many clinical and nonclinical applications. Transplantation pathology is a highly specialized field in which the majority ...of practicing pathologists do not have sufficient expertise to handle critical needs. In this context, digital pathology has proven to be useful as it allows for timely access to expert second-opinion teleconsultation. The aim of this study was to review the experience of the application of digital pathology to the field of transplantation. Methods: Papers on this topic were retrieved using PubMed as a search engine. Inclusion criteria were the presence of transplantation setting and the use of any type of digital image with or without the use of image analysis tools; the search was restricted to English language papers published in the 25 years until December 31, 2018. Results: Literature regarding digital transplant pathology is mostly about the digital interpretation of posttransplant biopsies (75 vs. 19), with 15/75 (20%) articles focusing on agreement/reproducibility. Several papers concentrated on the correlation between biopsy features assessed by digital image analysis (DIA) and clinical outcome (45/75, 60%). Whole-slide imaging (WSI) only appeared in recent publications, starting from 2011 (13/75, 17.3%). Papers dealing with preimplantation biopsy are less numerous, the majority (13/19, 68.4%) of which focus on diagnostic agreement between digital microscopy and light microscopy (LM), with WSI technology being used in only a small quota of papers (4/19, 21.1%). Conclusions: Overall, published studies show good concordance between digital microscopy and LM modalities for diagnosis. DIA has the potential to increase diagnostic reproducibility and facilitate the identification and quantification of histological parameters. Thus, with advancing technology such as faster scanning times, better image resolution, and novel image algorithms, it is likely that WSI will eventually replace LM.
The recent years have been characterised by a rapid development of whole slide imaging (WSI) especially in its applications to histology. The application of WSI technology to cytology is less common ...because of technological problems related to the three‐dimensional nature of cytology preparations (which requires capturing of z‐stack information, with an increase in file size and usability issues in viewing cytological preparations). The aim of this study is to provide a review of the literature on the use of digital cytology and provide an overview of cytological applications of WSI in current practice as well as identifying areas for future development.
Compared to digital histology, Whole Slide Imaging (WSI) in cytology requires a different methodological and technical approach. Increasing of scanning time, file size and screening time are just some of the issues arising from the multi z‐stack levels scanning necessary to focus all the cells dispersed in the 3D structure of a cytological preparation. Despite this cytological WSI is used in several fields for teaching, training, research, documentation and, in some cases, also for primary diagnosis.
Patients with isolated mediastinal lymphadenopathy (IML) are a common presentation to physicians, and mediastinoscopy is traditionally considered the "gold standard" investigation when a pathological ...diagnosis is required. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is established as an alternative to mediastinoscopy in patients with lung cancer.
To determine the efficacy and health care costs of EBUS-TBNA as an alternative initial investigation to mediastinoscopy in patients with isolated IML.
Prospective multicenter single-arm clinical trial of 77 consecutive patients with IML from 5 centers between April 2009 and March 2011. All patients underwent EBUS-TBNA. If EBUS-TBNA did not provide a diagnosis, then participants underwent mediastinoscopy.
EBUS-TBNA prevented 87% of mediastinoscopies (95% confidence interval CI, 77-94%; P < 0.001) but failed to provide a diagnosis in 10 patients (13%), all of whom underwent mediastinoscopy. The sensitivity and negative predictive value of EBUS-TBNA in patients with IML were 92% (95% CI, 83-95%) and 40% (95% CI, 12-74%), respectively. One patient developed a lower respiratory tract infection after EBUS-TBNA, requiring inpatient admission. The cost of the EBUS-TBNA procedure per patient was £1,382 ($2,190). The mean cost of the EBUS-TBNA strategy was £1,892 ($2,998) per patient, whereas a strategy of mediastinoscopy alone was significantly more costly at £3,228 ($5,115) per patient (P < 0.001). The EBUS-TBNA strategy is less costly than mediastinoscopy if the cost per EBUS-TBNA procedure is less than £2,718 ($4,307) per patient.
EBUS-TBNA is a safe, highly sensitive, and cost-saving initial investigation in patients with IML. Clinical trial registered with ClinicalTrials.gov (NCT00932854).
Purpose Retrospective studies indicate that expression of excision repair cross complementing group 1 (ERCC1) protein is associated with platinum resistance and survival in non-small-cell lung cancer ...(NSCLC). We conducted the first randomized trial, to our knowledge, to evaluate ERCC1 prospectively and to assess the superiority of nonplatinum therapy over platinum doublet therapy for ERCC1-positive NSCLC as well as noninferiority for ERCC1-negative NSCLC. Patients and Methods This trial had a marker-by-treatment interaction phase III design, with ERCC1 (8F1 antibody) status as a randomization stratification factor. Chemonaïve patients with NSCLC (stage IIIB and IV) were eligible. Patients with squamous histology were randomly assigned to cisplatin and gemcitabine or paclitaxel and gemcitabine; nonsquamous patients received cisplatin and pemetrexed or paclitaxel and pemetrexed. Primary end point was overall survival (OS). We also evaluated an antibody specific for XPF (clone 3F2). The target hazard ratio (HR) for patients with ERCC1-positive NSCLC was ≤ 0.78. Results Of patients, 648 were recruited (177 squamous, 471 nonsquamous). ERCC1-positive rates were 54.5% and 76.7% in nonsquamous and squamous patients, respectively, and the corresponding XPF-positive rates were 70.5% and 68.5%. Accrual stopped early in 2012 for squamous patients because OS for nonplatinum therapy was inferior to platinum therapy (median OS, 7.6 months paclitaxel and gemcitabine v 10.7 months cisplatin and gemcitabine; HR, 1.46; P = .02). Accrual for nonsquamous patients halted in 2013. Median OS was 8.0 (paclitaxel and pemetrexed) versus 9.6 (cisplatin and pemetrexed) months for ERCC1-positive patients (HR, 1.11; 95% CI, 0.85 to 1.44), and 10.3 (paclitaxel and pemetrexed) versus 11.6 (cisplatin and pemetrexed) months for ERCC1-negative patients (HR, 0.99; 95% CI, 0.73 to 1.33; interaction P = .64). OS HR was 1.09 (95% CI, 0.83 to 1.44) for XPF-positive patients, and 1.39 (95% CI, 0.90 to 2.15) for XPF-negative patients (interaction P = .35). Neither ERCC1 nor XPF were prognostic: among nonsquamous patients, OS HRs for positive versus negative were ERCC1, 1.11 ( P = .32), and XPF, 1.08 ( P = .55). Conclusion Superior outcomes were observed for patients with squamous histology who received platinum therapy compared with nonplatinum chemotherapy; however, selecting chemotherapy by using commercially available ERCC1 or XPF antibodies did not confer any extra survival benefit.
To investigate the potential of optical coherence tomography (OCT) to distinguish between normal and pathologic thyroid tissue, 3D OCT images were acquired on ex vivo thyroid samples from adult ...subjects (n=22) diagnosed with a variety of pathologies. The follicular structure was analyzed in terms of count, size, density and sphericity. Results showed that OCT images highly agreed with the corresponding histopatology and the calculated parameters were representative of the follicular structure variation. The analysis of OCT volumes provides quantitative information that could make automatic classification possible. Thus, OCT can be beneficial for intraoperative surgical guidance or in the pathology assessment routine.
Background
To the authors' knowledge, the impact of the coronavirus disease 2019 (COVID‐19) pandemic on cytopathology practices worldwide has not been investigated formally. In the current study, ...data from 41 respondents from 23 countries were reported.
Methods
Data regarding the activity of each cytopathology laboratory during 4 weeks of COVID‐19 lockdown were collected and compared with those obtained during the corresponding period in 2019. The overall number and percentage of exfoliative and fine‐needle aspiration cytology samples from each anatomic site were recorded. Differences in the malignancy and suspicious rates between the 2 periods were analyzed using a meta‐analytical approach.
Results
Overall, the sample volume was lower compared with 2019 (104,319 samples vs 190,225 samples), with an average volume reduction of 45.3% (range, 0.1%‐98.0%). The percentage of samples from the cervicovaginal tract, thyroid, and anorectal region was significantly reduced (P < .05). Conversely, the percentage of samples from the urinary tract, serous cavities, breast, lymph nodes, respiratory tract, salivary glands, central nervous system, gastrointestinal tract, pancreas, liver, and biliary tract increased (P < .05). An overall increase of 5.56% (95% CI, 3.77%‐7.35%) in the malignancy rate in nongynecological samples during the COVID‐19 pandemic was observed. When the suspicious category was included, the overall increase was 6.95% (95% CI, 4.63%‐9.27%).
Conclusions
The COVID‐19 pandemic resulted in a drastic reduction in the total number of cytology specimens regardless of anatomic site or specimen type. The rate of malignancy increased, reflecting the prioritization of patients with cancer who were considered to be at high risk. Prospective monitoring of the effect of delays in access to health services during the lockdown period is warranted.
The coronavirus disease 2019 (COVID‐19) pandemic has resulted in a drastic reduction in the total number of cytology specimens obtained regardless of anatomic site or specimen type. The rate of malignancy has increased, reflecting the prioritization of patients with cancer who are considered to be at high risk. Prospective monitoring of the effect of delays on access to health services during the lockdown period is warranted.
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