3616 Background: MSI due to mismatch repair defects accounts for 15-20% of all CC, has high prognostic and predictive value and is broadly utilized in treatment decisions. Artificial intelligence (AI) integrated, label-free quantum cascade laser (QCL) based infrared (IR) imaging resolves spatial and molecular alterations such as MSI in unstained cancer tissue sections. We aimed to evaluate the method for microsatellite instability/stability (MSI/MSS) classification in samples from the prospective multicenter AIO CPP registry trial. Methods: Paraffin-embedded unstained cancer tissue slides from patients (pts.) participating in CPP were measured (avg. 30 min/slide) and analyzed. The cohort was split into training (train), test (test), and validation (vali) sets. Cancer regions were first preselected based on a self-developed convolutional neural network (CNN) CompSegNet (Schuhmacher, medrxiv 2021). A VGG-16 CNN then classified MSI/MSS in these regions. Endpoints were area under receiver operating characteristic (AUROC) and area under precision recall curve (AUPRC). Results: 547 pts. (train n=331, test n=69, vali n=147) were analyzed. The baseline characteristics for the sub-cohorts are illustrated in the table. Mutation (MT) status: RAS MT: train 30% / test 30% / vali 37%; BRAF MT: train 27% / test 23% / vali 14%. The preselection of cancer regions reached a validation AUROC of 1.0. The subsequent MSI/MSS classifier reached a validation AUROC of 0.9 and AUPRC of 0.74 (sensitivity 85%, specificity 84%). Conclusions: Our multicenter approach using AI integrated label-free IR imaging provides an automated, fast, and reliable classification for MSI/MSS with an AUROC of 0.9 (sensitivity 85%, specificity 84%) almost comparable to the present gold standard immunohistochemistry. The method described here requires less samples for training when compared to other AI approaches which could facilitate the development of prognostic/predictive classifiers in the setting of randomized controlled trials. This novel technique may support further understanding of the increasingly important MSI CC cohort and support treatment decisions e.g. in specific subgroups such as targetable fusions. We expect our approach to be a broadly applicable diagnostic tool in the future.[Table: see text]
When asbestos fibers are inhaled, asbestos bodies can form in the lungs with the involvement of macrophages. It can take decades from the last exposure to the onset of an asbestos-related disease.
Purpose: Microsatellite instability (MSI) due to mismatch repair (MMR) defects accounts for 15-20% of colon cancers (CC). MSI testing is currently standard of care in CC with immunohistochemistry of the four MMR-proteins representing the gold standard. Instead, label-free quantum cascade laser (QCL) based infrared (IR) imaging combined with artificial intelligence (AI) may classify MSI/microsatellite stability (MSS) in unstained tissue sections user-independently and tissue preserving. Methods: Paraffin-embedded unstained tissue sections of early CC from patients participating in the multicentre AIO ColoPredict Plus (CPP) 2.0 registry were analysed after dividing into three groups (training, test, validation). IR images of tissue sections using QCL-IR microscopes were classified by AI (convolutional neural networks, CNN) using a two-step approach. The first CNN (modified U-Net) detected areas of cancer while the second CNN (VGG-Net) classified MSI/MSS. Endpoints were area under receiver operating characteristic (AUROC) and area under precision recall characteristic (AUPRC). Results: The cancer detection in the first step was based on 629 patients (train n=273, test n=138, validation n=218). Resulting classification AUROC was 1.0 for the validation dataset. The second step classifying MSI/MSS was performed on 547 patients (train n=331, test n=69, validation n=147) reaching AUROC and AUPRC of 0.9 and 0.74, respectively, for the validation cohort. Conclusion: Our novel label-free digital pathology approach accurately and rapidly classifies MSI vs. MSS. The tissue sections analysed were not processed leaving the sample unmodified for subsequent analyses. Our approach demonstrates an AI-based decision support tool potentially driving improved patient stratification and precision oncology in the future.
3626 Background: CRC still is one of the leading causes of cancer related death though prognosis has improved through guideline based management. The COVID-19 pandemic lead to re-allocation of resources subordinating all sections of care for CRC patients. We present data on changes of CRC care during the pandemic from 22 German AIO CC and our high volume Institute of Pathology (pathology). Methods: Data was collected retrospectively comparing the months (mo) of the first wave (fw) (4-6/2020) and second wave (sw) (11-12/2020) of the pandemic with corresponding periods (cp) in 2019 focusing on the number of precancerous (ICD-O/0+2) and malignant (ICD-O/3+6) colorectal lesions (CRL) diagnosed by our pathology, the number/stage of primary diagnoses (PD) and the number of surgeries (surg) at AIO CC. There, quality criteria of CRC care were also assessed (number of PD discussed within a multidisciplinary tumor board (tb), received social service (soc)/ psychological (psy) counseling or recruited into a clinical trial). Statistical analysis was performed using students t-test for paired data. Results: Numbers of CRL detected upon histology (row 1-3), number of cases, surg and quality criteria from AIO CC (row 4-9) are displayed in the table. We saw a dip in diagnosed CRL and number of surg (p=0.007) only during fw, whereas PD dipped significantly in both waves. A significant reduction in diagnosis of stage III CRC was detected for 2019 vs. 2020 (p=0.001), not for other stages. Quality criteria showed a significant reduction in clinical trial inclusion, a small dip in soc/psy counseling and persistently high tb presentation. Conclusions: We detected a significant decrease of premalignant lesions and primary cancers during the first year of the pandemic which may impact cancer mortality in the future. Certified German CC provided CRC care with significant reduction in clinical trial inclusion only, suggesting high stability of established certified cancer care infrastructure.[Table: see text]
Case Reports1 August 1949KAPOSI'S SARCOMA WITH SECONDARY INVOLVEMENT OF THE JEJUNUM, PERFORATION AND PERITONITISNATHAN MITCHELL, M.D., ISIDORE A. FEDER, M.D., F.A.C.P.NATHAN MITCHELL, M.D.Search for more papers by this author, ISIDORE A. FEDER, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-31-2-324 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptSince Kaposi's original description of multiple hemorrhagic sarcoma of the skin in 1872, more than 600 cases have been reported in the literature. In the great majority of these cases the skin has been primarily affected. A large number progress slowly for many years and at autopsy show no spread beyond the cutaneous site. However, the finding of sarcomatous deposits in the viscera is a common one. Almost every organ of the body has been implicated. In addition to the skin the most frequent sites of involvement are the penis, the gastrointestinal tract, the upper and lower respiratory tracts and...Bibliography1. STATS D: The visceral manifestations of Kaposi's sarcoma, Jr. Mt. Sinai Hosp., 1946, xii, 971-983. Google Scholar2. NESBITTMARKZIMMERMAN SPFHM: Disseminated idiopathic hemorrhagic sarcoma (Kaposi's disease); report of case with necropsy findings, Ann. Int. Med., 1945, xxii, 601-605. Google Scholar3. AEGERTERPEALE EEAR: Kaposi's sarcoma; a critical survey, Arch. Path., 1942, xxxiv, 413-422. Google Scholar4. TEDESCHIFOLSOMCARNICELLI CGHFTJ: Visceral Kaposi's disease, Arch. Path., 1947, xliii, 335-357. Google Scholar5. WILLIS RA: The spread of tumors in the human body, 1934, J. & A. Churchill, London. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Brooklyn, N. Y.*Received for publication July 23, 1947.From the Departments of Pathology and Medicine of the Beth El Hospital. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byEnfermedad de KaposiMalignant DiseaseIntestinal Kaposi's without AIDSMalabsorption Syndromes and Intestinal Protein LossKaposi's sarcoma and lymphoma of the gut in AIDSGastrointestinal and Hepatobiliary Neoplasms in AIDSKaposi’s SarcomaGastrointestinal Kaposi's sarcoma in patients with acquired immunodeficiency syndromeKaposi's sarcomaKaposi’s Sarcoma Presenting with Diarrhea and Protein-Losing EnteropathyStudies in Kaposi's sarcoma. Postmortem findings and disease patterns in womenKaposi's Sarcoma Presenting with Abdominal SymptomsKaposi's sarcoma 1 August 1949Volume 31, Issue 2Page: 324-329KeywordsAutopsyGastrointestinal tractHospital medicineJejunumKaposi sarcomaPenisPeritonitisRespiratory systemSarcoma ePublished: 1 December 2008 Issue Published: 1 August 1949 PDF downloadLoading ...
Abstract Background: Molecular tests predicting outcome of breast cancer patients may be useful for treatment decisions in addition to standard clinicopathologic features. Methods: Using human genome HG-U133A array and qRT-PCR datasets, we developed and validated a gene-expression signature predicting the likelihood of distant recurrence in postmenopausal, early-stage breast cancer patients with estrogen receptor-positive, HER2-negative tumors treated with adjuvant endocrine therapy. RNA levels assessed by qRT-PCR in formalin-fixed paraffin-embedded tumor specimens were used to calculate a risk score (T5) and to determine a risk group (low or high) for each patient. The prospectively defined T5 risk score was then validated independently in patients from two large randomized phase III trials. Distant recurrence-free survival and overall survival were analyzed with Cox models adjusted for clinicopathological factors. The primary endpoint was time to distant recurrence. Results: In a training set of 964 tumors, we identified a gene-expression signature consisting of three proliferation-related genes (BIRC5, UBE2C, DHCR7), five estrogen-regulated genes (RBBP8, IL6ST, AZGP1, MGP, STC2), and three reference genes (CALM2, OAZ1, RPL37A). For the validation, RNA analysis was possible in 1702 of 1725 (99%) tumors of both validation sets. Women were classified as having low risk (n=832; 49%) or high risk (n=870; 51%) by the T5 risk score. The T5 risk score provided prognostic information independent from clinicopathologic risk as estimated by Adjuvant!Online or Ki67 labeling index. Patients with a higher T5 risk score had a significantly shorter time to distant recurrence (adjusted hazard ratio, 1.24; 95% confidence interval [CI], 1.15 to 1.33; P<0.001) and overall survival (adjusted hazard ratio, 1.13; 95% CI, 1.06 to 1.19; P<0.001) compared to patients with a lower T5 risk score. The addition of the risk characterized by the T5 risk score to the clinicopathological risk resulted in 10-year distant recurrence-free survival rates of 95% in combined low risk patients and 82% in combined high risk patients (P<0.001). Conclusions: Using formalin-fixed paraffin-embedded tumor specimens, the multigene T5 risk score provides prognostic information independent of Adjuvant!Online or Ki67 labeling index. By combining the T5 risk score with clinicopathological risk, we were able to accurately identify breast cancer patients with low risk or high risk for distant recurrence. Using this new easy-to-use multigene tool in clinical practice will assist in optimizing adjuvant therapy by reducing both undertreatment and overtreatment and thus improves outcome and quality of life of patients with early-stage breast cancer. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-10-07.
