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Background: Minimally invasive (MIS) cholecystectomies have become standard due to patient and hospital advantages; however, this approach is not always achievable. Acute and gangrenous cholecystitis increase the likelihood of conversion from MIS to open cholecystectomy. This study aims to examine patient and hospital factors underlying differential utilization of MIS vs open cholecystectomies indicated for acute cholecystitis., Methods: This is a retrospective, observational cohort study of patients with acute cholecystitis who underwent a cholecystectomy between 2016 and 2018 identified from the California Office of Statewide Health Planning and Development database. Univariate analysis and multivariable logistic regression models were used to analyze patient, geographic, and hospital variables as well as surgical approach., Results: Our total cohort included 53,503 patients of which 98.4% (n = 52,673) underwent an initial minimally invasive approach and with a conversion rate of 3.3% (n = 1,759). On multivariable analysis advancing age increased the likelihood of either primary open (age 40 to < 65 aOR 2.17; ≥ 65 aOR 3.00) or conversion to open cholecystectomy (age 40 to < 65 aOR 2.20; ≥ 65 aOR 3.15). Similarly, male sex had higher odds of either primary open (aOR 1.70) or conversion to open cholecystectomy (aOR 1.84). Hospital characteristics increasing the likelihood of either primary open or conversion to open cholecystectomy included teaching hospitals (aOR 1.37 and 1.28, respectively) and safety-net hospitals (aOR 1.46 and 1.33, respectively)., Conclusions: With respect to cholecystectomy, it is well-established that a minimally invasive surgical approach is associated with superior patient outcomes. Our study focused on the diagnosis of acute cholecystitis and identified increasing age as well as male sex as significant factors associated with open surgery. Teaching and safety-net hospital status were also associated with differential utilization of open, conversion-to-open, and MIS. These findings suggest the potential to create and apply strategies to further minimize open surgery in the setting of acute cholecystitis., Competing Interests: Declarations. Disclosures: Tess C Huy, MD, Rivfka Shenoy, MD, Mark Girgis, MD, James S Tomlinson, MD, PhD, and Marcia M Russell, MD have no conflicts of interest or financial ties to disclose., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Pancreatic neuroendocrine tumors (pNETs) are genomically diverse tumors. The management of newly diagnosed well-differentiated pNETs is limited by a lack of sensitivity of existing biomarkers for prognostication. Our goal was to investigate the potential utility of genetic markers as a predictor of progression-free survival (PFS) and recurrence-free survival (RFS)., Methods: Whole-exome sequencing of resected well-differentiated, low and intermediate-grade (G1 and G2) pNETs and normal adjacent tissue from patients who underwent resection from 2005 to 2015 was performed. Genetic alterations were classified using pan-genomic and oncogenic pathway classifications. Additional samples with genetic and clinicopathologic data available were obtained from the publicly available International Cancer Genome Consortium (ICGC) database and included in the analysis. The prognostic relevance of these genomic signatures on PFS and RFS was analyzed., Results: Thirty-one patients who underwent resection for pNET were identified. Genomic analysis of mutational, copy number, cytogenetic, and complex phenomena revealed similar patterns to prior studies of pNETs with relatively few somatic gene mutations but numerous instances of copy number changes. Analysis of genomic and clinicopathologic outcomes using the combined data from our study as well as the ICGC pNET cohort (n = 124 patients) revealed that the recurrent pattern of whole chromosome loss (RPCL) and metastatic disease were independently associated with disease progression. When evaluating patients with local disease at the time of resection, RPCL and alterations in the TGFβ oncogenic pathway were independently associated with the risk of recurrence., Conclusions: Well-differentiated pNETs are genomically diverse tumors. Pathway signatures may be prognostic for predicting disease progression and recurrence., (© 2024 The Author(s). Journal of Surgical Oncology published by Wiley Periodicals LLC.)

Background: Pancreaticoduodenectomy (PD) is complex procedure with high morbidity in the elderly. This retrospective study aimed to compare post-operative outcomes in patients ≥75 years of age who underwent robot-assisted (RA)PD and open PD., Methods: We analyzed 2502 patients ≥75 years of age who underwent PD from 2015 to 2018 in the National Surgical Quality Improvement Program (NSQIP) database. RAPD and open PD patients were propensity score matched 1:5 to assess the 30-day outcomes of interest: postoperative complications, length of stay, discharge destination, and readmissions., Results: Of 725 matched patients, 110 underwent RAPD, 615 OPD, and 12 were converted to an open operation. Post-operative outcomes were largely similar between cohorts. RAPD was associated a shorter length of stay (median 8 days, interquartile range [IQR] 6 to 11) than OPD (median 8 days, IQR 7 to 13) (p = 0.003). However, RAPD was associated with more readmissions (28.1% vs. 17.7%; p = 0.02)., Conclusions: RAPD in patients ≥75 years of age appears to be safe and has a similar complication profile to open PD. Randomized or well-designed prospective matched studies are needed to confirm these findings., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Early cancer detection by cell-free DNA faces multiple challenges: low fraction of tumor cell-free DNA, molecular heterogeneity of cancer, and sample sizes that are not sufficient to reflect diverse patient populations. Here, we develop a cancer detection approach to address these challenges. It consists of an assay, cfMethyl-Seq, for cost-effective sequencing of the cell-free DNA methylome (with > 12-fold enrichment over whole genome bisulfite sequencing in CpG islands), and a computational method to extract methylation information and diagnose patients. Applying our approach to 408 colon, liver, lung, and stomach cancer patients and controls, at 97.9% specificity we achieve 80.7% and 74.5% sensitivity in detecting all-stage and early-stage cancer, and 89.1% and 85.0% accuracy for locating tissue-of-origin of all-stage and early-stage cancer, respectively. Our approach cost-effectively retains methylome profiles of cancer abnormalities, allowing us to learn new features and expand to other cancer types as training cohorts grow., (© 2022. The Author(s).)

Well-preserved molecular cargo in circulating extracellular vesicles (EVs) offers an ideal material for detecting oncogenic gene alterations in cancer patients, providing a noninvasive diagnostic solution for detection of disease status and monitoring treatment response. Therefore, technologies that conveniently isolate EVs with sufficient efficiency are desperately needed. Here, a lipid labeling and click chemistry-based EV capture platform ("Click Beads"), which is ideal for EV message ribonucleic acid (mRNA) assays due to its efficient, convenient, and rapid purification of EVs, enabling downstream molecular quantification using reverse transcription digital polymerase chain reaction (RT-dPCR) is described and demonstrated. Ewing sarcoma protein (EWS) gene rearrangements and kirsten rat sarcoma viral oncogene homolog (KRAS) gene mutation status are detected and quantified using EVs isolated by Click Beads and matched with those identified in biopsy specimens from Ewing sarcoma or pancreatic cancer patients. Moreover, the quantification of gene alterations can be used for monitoring treatment responses and disease progression., (© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Human cancers are often complicated with increased incidences of blood vessel occlusion, which are mostly insensitive to anticoagulation therapy. We searched for causal factors of cancer-associated embolism. A total of 2,017 blood samples was examined for visible abnormalities. Examined were peripheral blood samples from cancer patients who were about to undergo surgical treatment for genitourinary, breast, gastrointestinal or abdominal tumors. Samples from ambulatory patients being treated for recurrent or castration-resistant prostate cancers were included in the study. The lipid-rich nature was studied with lipophilic stains and lipid panel analysis, while surface membrane was assessed with specific staining and antibody detection. We identified a new entity, lipid droplet-like objects or circulating fatty objects (CFOs), visible in the blood samples of many cancer patients, with the potential of causing embolism. CFOs were defined as lipid-rich objects with a membrane, capable of gaining in volume through interaction with peripheral blood mononuclear cells in ex vivo culture. Blood samples from pancreatic cancer patients were found to have the highest CFO incidence and largest CFO numbers. Most noticeably, CFOs from many pancreatic cancer samples presented as large clusters entangled in insoluble fiber networks, suggestive of intravascular clotting. This study identifies CFO as an abnormal entity in cancer patient blood, and a contributory factor to intravascular embolism during cancer development and progression., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Nissen, Zhang, Shao, Chu, Huynh, Posadas, Tomlinson, Lewis and Pandol.)