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Item Artificial Intelligence in Pancreatic Intraductal Papillary Mucinous Neoplasm Imaging: A Systematic Review(medRxiv, 2025-01-09) Qadir, Muhammad Ibtsaam; Baril, Jackson A.; Yip-Schneider, Michele T.; Schonlau, Duane; Tran, Thi Thanh Thoa; Schmidt, C. Max; Kolbinger, Fiona R.; Surgery, School of MedicineBackground: Based on the Fukuoka and Kyoto international consensus guidelines, the current clinical management of intraductal papillary mucinous neoplasm (IPMN) largely depends on imaging features. While these criteria are highly sensitive in detecting high-risk IPMN, they lack specificity, resulting in surgical overtreatment. Artificial Intelligence (AI)-based medical image analysis has the potential to augment the clinical management of IPMNs by improving diagnostic accuracy. Methods: Based on a systematic review of the academic literature on AI in IPMN imaging, 1041 publications were identified of which 25 published studies were included in the analysis. The studies were stratified based on prediction target, underlying data type and imaging modality, patient cohort size, and stage of clinical translation and were subsequently analyzed to identify trends and gaps in the field. Results: Research on AI in IPMN imaging has been increasing in recent years. The majority of studies utilized CT imaging to train computational models. Most studies presented computational models developed on single-center datasets (n=11,44%) and included less than 250 patients (n=18,72%). Methodologically, convolutional neural network (CNN)-based algorithms were most commonly used. Thematically, most studies reported models augmenting differential diagnosis (n=9,36%) or risk stratification (n=10,40%) rather than IPMN detection (n=5,20%) or IPMN segmentation (n=2,8%). Conclusion: This systematic review provides a comprehensive overview of the research landscape of AI in IPMN imaging. Computational models have potential to enhance the accurate and precise stratification of patients with IPMN. Multicenter collaboration and datasets comprising various modalities are necessary to fully utilize this potential, alongside concerted efforts towards clinical translation.Item Diagnosis and Management of Pancreatic Cysts: A Comprehensive Review of the Literature(MDPI, 2023-02-02) Singh, Ritu R.; Gopakumar, Harishankar; Sharma, Neil R.; Medicine, School of MedicineThe prevalence of pancreatic cysts has been rising due to the widespread use of cross-sectional imaging (CT scan and MRI) of the abdomen. While most pancreatic cysts are benign and do not require treatment or surveillance, a significant minority are premalignant and rarely malignant. The risk stratification of these lesions is not straightforward, and individual risk assessment, cyst size, distribution, and alarming morphologic features (when present) can guide the next steps in management. Neoplastic pancreatic cysts are mucinous or non-mucinous. Endoscopic ultrasound with fine-needle aspiration is often required to classify pancreatic cysts into mucinous and non-mucinous cysts and to assess the malignant potential. Advances in endoscopic techniques (confocal laser endomicroscopy, microforceps biopsy) can provide a definitive diagnosis of pancreatic cysts in some cases; however, the use of these techniques involves a higher risk of adverse events.Item Multi-region Whole Exome Sequencing of Intraductal Papillary Mucinous Neoplasms Reveals Frequent Somatic KLF4 Mutations Predominantly in Low-Grade Regions(BMJ, 2021) Fujikura, Kohei; Hosoda, Waki; Felsenstein, Matthäus; Song, Qianqian; Reiter, Johannes G.; Zheng, Lily; Guthrie, Violeta Beleva; Rincon, Natalia; Molin, Marco Dal; Dudley, Jonathan; Cohen, Joshua D.; Wang, Pei; Fischer, Catherine G.; Braxton, Alicia M.; Noë, Michaël; Jongepier, Martine; Castillo, Carlos Fernández-del; Mino-Kenudson, Mari; Schmidt, C. Max; Yip-Schneider, Michele T.; Lawlor, Rita T.; Salvia, Roberto; Roberts, Nicholas J.; Thompson, Elizabeth D.; Karchin, Rachel; Lennon, Anne Marie; Jiao, Yuchen; Wood, Laura D.; Surgery, School of MedicineObjective: Intraductal papillary mucinous neoplasms (IPMNs) are non-invasive precursor lesions that can progress to invasive pancreatic cancer and are classified as low-grade or high-grade based on the morphology of the neoplastic epithelium. We aimed to compare genetic alterations in low-grade and high-grade regions of the same IPMN in order to identify molecular alterations underlying neoplastic progression. Design: We performed multiregion whole exome sequencing on tissue samples from 17 IPMNs with both low-grade and high-grade dysplasia (76 IPMN regions, including 49 from low-grade dysplasia and 27 from high-grade dysplasia). We reconstructed the phylogeny for each case, and we assessed mutations in a novel driver gene in an independent cohort of 63 IPMN cyst fluid samples. Results: Our multiregion whole exome sequencing identified KLF4, a previously unreported genetic driver of IPMN tumorigenesis, with hotspot mutations in one of two codons identified in >50% of the analyzed IPMNs. Mutations in KLF4 were significantly more prevalent in low-grade regions in our sequenced cases. Phylogenetic analyses of whole exome sequencing data demonstrated diverse patterns of IPMN initiation and progression. Hotspot mutations in KLF4 were also identified in an independent cohort of IPMN cyst fluid samples, again with a significantly higher prevalence in low-grade IPMNs. Conclusion: Hotspot mutations in KLF4 occur at high prevalence in IPMNs. Unique among pancreatic driver genes, KLF4 mutations are enriched in low-grade IPMNs. These data highlight distinct molecular features of low-grade and high-grade dysplasia and suggest diverse pathways to high-grade dysplasia via the IPMN pathway.Item Splenic-vasculature involvement is associated with poor prognosis in resected distal pancreatic cancer(Oxford University Press, 2020-11-24) Yin, Feng; Saad, Mohammed; Lin, Jingmei; Jackson, Christopher R.; Ren, Bing; Lawson, Cynthia; Karamchandani, Dipti M.; Bernabeu, Belen Quereda; Jiang, Wei; Dhir, Teena; Zheng, Richard; Schultz, Christopher W.; Zhang, Dongwei; Thomas, Courtney L.; Zhang, Xuchen; Lai, Jinping; Schild, Michael; Zhang, Xuefeng; Xie, Hao; Liu, Xiuli; Pathology and Laboratory Medicine, School of MedicineBackground: Distal pancreatic carcinoma is one of the most lethal cancers largely due to its high incidence of distant metastasis. This study aims to assess the prognostic value of splenic-vasculature involvement in resected distal pancreatic carcinoma. Methods: In this retrospective study, we collected the clinicopathologic information of 454 patients with pancreatic cancer and performed univariate and multivariate analyses to identify factors associated with progression-free survival (PFS) and overall survival (OS), with an emphasis on the prognostic value of splenic-artery and -vein involvement. Results: Univariate analysis revealed that larger tumor size, non-intraductal papillary mucinous neoplasm (non-IPMN)-associated adenocarcinoma, poor differentiation, stage pT3, nodal metastasis, lymphovascular invasion, perineural invasion, and pathologic and radiographic evidence of splenic-vein invasion were significantly associated with shorter PFS and OS (all P < 0.05). Multivariate analysis confirmed non-IPMN-associated adenocarcinoma, stage pT3, stage pN1-2, and post-operative adjuvant chemotherapy as independent risk factors for both PFS and OS, and larger tumor size and radiographic evidence of splenic-artery invasion as predictors of PFS only. Conclusion: Guidelines should be developed for a uniform approach with regard to the examination and reporting of the status of the splenic vasculature when dealing with distal-pancreatic-cancer specimens.