Impact of Tumor size in Predicting Outcome in Patients with Ampullary Cancer

Journal of Gastrointestinal Cancer · 2026-03-17

Assessment of nodal staging and risk factors for nodal involvement in gallbladder cancer

BJS Open · 2025-05-07 · 3 citations

BACKGROUND: Nodal assessment in gallbladder cancer remains challenging, particularly in incidental gallbladder cancer. This understages the number of patients with node-positive disease, resulting in prognostic inaccuracy and insufficient adjuvant treatment. This study aimed to identify risk factors for positive nodes in gallbladder cancer and to compare prognostic discrimination of available nodal staging parameters. METHODS: This international cohort study assessed gallbladder cancer resections undertaken between 1 January 2010 and 31 December 2020. Logistic regression was used to identify risk factors for node-positive status and develop a risk prediction score for positive nodes. Nodal staging models, including nodal site, number of positive nodes, and positive node ratio were compared for greatest prognostic discrimination in gallbladder cancer. RESULTS: A total of 3676 patients underwent gallbladder cancer resection across 133 centres in 41 countries. Tumour (T) stage (T2, P = 0.012; T3, P = 0.002; and T4, P < 0.001), lymphovascular and perineural infiltration (P < 0.001), and tumour differentiation (P < 0.001) carried the greatest risk of positive nodes. These three parameters comprised the OMEGA Node Positivity Prediction Score (OMEGA-NOPPS) with C-statistics of 0.81 (95% confidence interval 0.78 to 0.84) in the training data set and 0.79 (0.73 to 0.85) in the test data set for identification of node-positive status, highlighting a ≥ 20% increased risk of positive nodes in poorly differentiated tumours with lymphovascular and perineural infiltration despite T1 disease. CONCLUSION: Data from this large multicentre study confirmed that the number of positive nodes is the most discriminative prognostic model for nodal staging in gallbladder cancer. OMEGA-NOPPS provides three simple parameters to stratify nodal involvement according to risk. Incidental gallbladder cancer with lymphovascular and perineural infiltration and poorly differentiated tumours, including early T stages, should be considered for further treatment.

Laser-Based Undulator Design for Soft X-ray Free Electron Laser

2024-01-01

We present an optical undulator design of a soft X-ray compact free electron laser with a laser-based undulator feasible with commercially available laser systems. We simulate the Inverse Compton Scattering process and investigate engineering constraints.

Laser Systems and Diagnostics for the ASU Compact X-ray Source

2024 · 2 citations

• Computer Science
• Physics
• Optics

We present recent commissioning results from the ASU Compact x-ray source (CXLS)- an inverse Compton source producing sub-picosecond hard x-rays. We discuss the x-ray source performance, flux, diagnostics, and designs for a future ICS source.

Supplementary Figure S3 from Establishment of Patient-Derived Succinate Dehydrogenase–Deficient Gastrointestinal Stromal Tumor Models for Predicting Therapeutic Response

2023-03-31

&lt;p&gt;Fig. S3. Recapitulation of transcriptional characteristics of parental tumors and SDH-deficiency by patient-derived mSDH GIST models. A. Scatter Plot of the first two principal components and associated percentage of variance they explain for each SDH-deficient tumor and cell culture, as well as GIST882. B. The normalized gene set activity score (y-axis) for each investigated signature in Figure 3B and 3H, is displayed for each SDH-deficient tumor and cell culture, as well as GIST882. C. mSDH GIST spheroids express higher levels of 5-mC than 5-hmC when compared to GIST882 cells stained with an antibody to 5-mC (red) or to 5-hmC (green) followed by imaging with confocal fluorescence microscopy. Nuclei were stained with DAPI (blue). Scale bar, 50 �m.&lt;/p&gt;

Supplementary Legend from Location of Gastrointestinal Stromal Tumor (GIST) in the Stomach Predicts Tumor Mutation Profile and Drug Sensitivity

2023-03-31

&lt;p&gt;Supplementary Legend&lt;/p&gt;

Supplementary Data from Anti-KIT DNA Aptamer for Targeted Labeling of Gastrointestinal Stromal Tumor

2023-04-03

&lt;p&gt;Supplementary Figure 1&lt;/p&gt;

Surgical outcomes of gallbladder cancer: the OMEGA retrospective, multicentre, international cohort study

EClinicalMedicine · 2023 · 55 citations

• Medicine
• Internal medicine
• Gastroenterology

Background: Gallbladder cancer (GBC) is rare but aggressive. The extent of surgical intervention for different GBC stages is non-uniform, ranging from cholecystectomy alone to extended resections including major hepatectomy, resection of adjacent organs and routine extrahepatic bile duct resection (EBDR). Robust evidence here is lacking, however, and survival benefit poorly defined. This study assesses factors associated with recurrence-free survival (RFS), overall survival (OS) and morbidity and mortality following GBC surgery in high income countries (HIC) and low and middle income countries (LMIC). Methods: The multicentre, retrospective Operative Management of Gallbladder Cancer (OMEGA) cohort study included all patients who underwent GBC resection across 133 centres between 1st January 2010 and 31st December 2020. Regression analyses assessed factors associated with OS, RFS and morbidity. Findings: On multivariable analysis of all 3676 patients, wedge resection and segment IVb/V resection failed to improve RFS (HR 1.04 [0.84-1.29], p = 0.711 and HR 1.18 [0.95-1.46], p = 0.13 respectively) or OS (HR 0.96 [0.79-1.17], p = 0.67 and HR 1.48 [1.16-1.88], p = 0.49 respectively), while major hepatectomy was associated with worse RFS (HR 1.33 [1.02-1.74], p = 0.037) and OS (HR 1.26 [1.03-1.53], p = 0.022). Furthermore, EBDR (OR 2.86 [2.3-3.52], p < 0.0010), resection of additional organs (OR 2.22 [1.62-3.02], p < 0.0010) and major hepatectomy (OR 3.81 [2.55-5.73], p < 0.0010) were all associated with increased morbidity and mortality. Compared to LMIC, patients in HIC were associated with poorer RFS (HR 1.18 [1.02-1.37], p = 0.031) but not OS (HR 1.05 [0.91-1.22], p = 0.48). Adjuvant and neoadjuvant treatments were infrequently used. Interpretation: In this large, multicentre analysis of GBC surgical outcomes, liver resection was not conclusively associated with improved survival, and extended resections were associated with greater morbidity and mortality without oncological benefit. Aggressive upfront resections do not benefit higher stage GBC, and international collaborations are needed to develop evidence-based neoadjuvant and adjuvant treatment strategies to minimise surgical morbidity and prioritise prognostic benefit. Funding: Cambridge Hepatopancreatobiliary Department Research Fund.

Figures S1-S2 from Location of Gastrointestinal Stromal Tumor (GIST) in the Stomach Predicts Tumor Mutation Profile and Drug Sensitivity

2023-03-31

&lt;p&gt;KIT vs non-KIT mutations from NCDB, morphology and age distributions&lt;/p&gt;

Data from KIT&lt;sup&gt;low&lt;/sup&gt; Cells Mediate Imatinib Resistance in Gastrointestinal Stromal Tumor

2023-04-03

&lt;div&gt;Abstract&lt;p&gt;Gastrointestinal stromal tumor (GIST) is commonly driven by oncogenic &lt;i&gt;KIT&lt;/i&gt; mutations that are effectively targeted by imatinib (IM), a tyrosine kinase inhibitor (TKI). However, IM does not cure GIST, and adjuvant therapy only delays recurrence in high-risk tumors. We hypothesized that GIST contains cells with primary IM resistance that may represent a reservoir for disease persistence. Here, we report a subpopulation of CD34&lt;sup&gt;+&lt;/sup&gt;KIT&lt;sup&gt;low&lt;/sup&gt; human GIST cells that have intrinsic IM resistance. These cells possess cancer stem cell-like expression profiles and behavior, including self-renewal and differentiation into CD34&lt;sup&gt;+&lt;/sup&gt;KIT&lt;sup&gt;high&lt;/sup&gt; progeny that are sensitive to IM treatment. We also found that TKI treatment of GIST cell lines led to induction of stem cell–associated transcription factors (&lt;i&gt;OCT4&lt;/i&gt; and &lt;i&gt;NANOG&lt;/i&gt;) and concomitant enrichment of the CD34&lt;sup&gt;+&lt;/sup&gt;KIT&lt;sup&gt;low&lt;/sup&gt; cell population. Using a data-driven approach, we constructed a transcriptomic-oncogenic map (Onco-GPS) based on the gene expression of 134 GIST samples to define pathway activation during GIST tumorigenesis. Tumors with low KIT expression had overexpression of cancer stem cell gene signatures consistent with our &lt;i&gt;in vitro&lt;/i&gt; findings. Additionally, these tumors had activation of the Gas6/AXL pathway and NF-κB signaling gene signatures. We evaluated these targets &lt;i&gt;in vitro&lt;/i&gt; and found that primary IM-resistant GIST cells were effectively targeted with either single-agent bemcentinib (AXL inhibitor) or bardoxolone (NF-κB inhibitor), as well as with either agent in combination with IM. Collectively, these findings suggest that CD34&lt;sup&gt;+&lt;/sup&gt;KIT&lt;sup&gt;low&lt;/sup&gt; cells represent a distinct, but targetable, subpopulation in human GIST that may represent a novel mechanism of primary TKI resistance, as well as a target for overcoming disease persistence following TKI therapy.&lt;/p&gt;&lt;/div&gt;