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Purpose: To determine the accuracy of final judgements of doctors at the emergency department (ED) and radiologists to differentiate between complicated and uncomplicated acute appendicitis, because these have different treatment options. Methods: This prospective, multicenter study included adult patients with imaging-confirmed acute appendicitis, operated with intention to appendectomy. Both doctors at ED and radiologists assessed appendicitis severity as a final judgement of "uncomplicated" or "complicated" appendicitis. Doctors at ED integrated clinical, laboratory, and imaging findings. Radiologists relied solely on imaging findings. Outcomes were accuracy of these judgements for diagnosis of complicated appendicitis compared to the reference standard by an adjudication committee. Results: After imaging, 1070 patients with confirmed acute appendicitis were included. Doctors at ED accurately labelled 656 of 701 (93.6%) patients with true uncomplicated appendicitis as uncomplicated, and 163 of 369 (44.2%) patients with true complicated appendicitis were labelled as complicated. Sensitivity, specificity, and positive and negative predictive values (PPV and NPV) for complicated appendicitis were 44.2%, 93.6%, and 78.4% and 76.1%, respectively. Comparable accuracy was found for the radiologist's assessment in 941 patients, with true positive rates of 92.2% (581 of 630 patients) for uncomplicated appendicitis and 46.6% (145 of 311 patients) for complicated appendicitis. Conclusion: More than half of all patients with true complicated appendicitis is incorrectly classified as uncomplicated appendicitis according to the judgements of doctors at ED, integrating clinical, laboratory, and imaging results, and of radiologists assessing diagnostic imaging. These judgements are thereby not sufficiently reliable in ruling out complicated appendicitis. [ABSTRACT FROM AUTHOR]

Neoadjuvant therapy (NAT) has become routine in patients with borderline resectable pancreatic cancer. Pathologists examine pancreatic cancer resection specimens to evaluate the effect of NAT. However, an automated scoring system to objectively quantify residual pancreatic cancer (RPC) is currently lacking. Herein, we developed and validated the first automated segmentation model using artificial intelligence techniques to objectively quantify RPC. Digitized histopathological tissue slides were included from resected pancreatic cancer specimens from 14 centers in 7 countries in Europe, North America, Australia, and Asia. Four different scanner types were used: Philips (56%), Hamamatsu (27%), 3DHistech (10%), and Leica (7%). Regions of interest were annotated and classified as cancer, non-neoplastic pancreatic ducts, and others. A U-Net model was trained to detect RPC. Validation consisted of by-scanner internal-external cross-validation. Overall, 528 unique hematoxylin and eosin (H & E) slides from 528 patients were included. In the individual Philips, Hamamatsu, 3DHistech, and Leica scanner cross-validations, mean F1 scores of 0.81 (95% CI, 0.77-0.84), 0.80 (0.78-0.83), 0.76 (0.65-0.78), and 0.71 (0.65-0.78) were achieved, respectively. In the meta-analysis of the cross-validations, the mean F1 score was 0.78 (0.71-0.84). A final model was trained on the entire data set. This ISGPP model is the first segmentation model using artificial intelligence techniques to objectively quantify RPC following NAT. The internally-externally cross-validated model in this study demonstrated robust performance in detecting RPC in specimens. The ISGPP model, now made publically available, enables automated RPC segmentation and forms the basis for objective NAT response evaluation in pancreatic cancer., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Around 15-30% of colorectal cancers (CRC) develop from sessile serrated lesions (SSLs). After many years of indolent growth, SSLs can develop dysplasia and rapidly progress to CRC through events that are only partially understood. We studied molecular events at the very early stages of progression of SSLs via the MLH1-proficient and deficient pathways to CRC. We collected a cohort of rare SSLs with a small focus (<10 mm) of dysplasia or cancer from the pathology archives of three hospitals. Whole-exome sequencing was performed on DNA from nonprogressed and progressed components of each SSL. Putative somatic driver mutations were identified in known cancer genes that were differentially mutated in the progressed component. All analyses were stratified by MLH1 proficiency. Forty-five lesions with a focus dysplasia or cancer were included, of which 22 (49%) were MLH1-deficient. Lesions had a median diameter of 10 mm (interquartile range [IQR] 8-15), while the progressed component had a median diameter of 3.5 mm (IQR 1.75-4.75). Tumor mutational burden (TMB) was high in MLH1-deficient lesions (23.9 mutations per MB) as compared to MLH1-proficient lesions (6.3 mutations per MB). We identified 34 recurrently mutated genes in MLH1-deficient lesions. Most prominently, ACVR2A and RNF43 were affected in 18/22 lesions, with mutations clustered in three hotspots. Most lesions with RNF43 mutations had concurrent mutations in ZNRF3. In MLH1-proficient lesions APC (10/23 lesions) and TP53 (6/23 lesions) were recurrently mutated. Our results show that the mutational burden is exceptionally high even in the earliest MLH1-deficient lesions. We demonstrate that hotspot mutations in ACVR2A and in the RNF43/ZNRF3 complex are extremely common in the early progression of SSLs along the MLH1-deficient serrated pathway, while APC and TP53 mutations are early events in the the MLH1-proficient pathway. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland., (© 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.)