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LBA490 Background: Biliary tract cancers (BTCs) are a heterogeneous group of malignancies with a dismal prognosis. Gemcitabine-based regimens are the standard of care in advanced disease, but median overall survival (OS) is roughly 12 months. The addition of albumin-bound paclitaxel to gemcitabine and cisplatin (GAP) demonstrated promising efficacy in a 60 patient, single-arm phase II study (Shroff et al, JAMA Oncol 2019), with observed median OS of 19.2 months. Methods: SWOG 1815 is a randomized, open-label, phase III trial comparing GAP to gemcitabine/cisplatin (GC). The study included newly diagnosed advanced BTC patients (pts), randomized 2:1 to GAP vs. GC. GAP included gemcitabine at 800 mg/m2, cisplatin at 25 mg/m2 and albumin-bound paclitaxel at 100 mg/m2 on days 1 and 8 of a 21-day cycle. GC included standard dosing of gemcitabine at 1000 mg/m2 and cisplatin at 25 mg/m2 on days 1 and 8 of a 21-day cycle. Pts were treated until progression. The primary endpoint was overall survival (OS) with a target hazard ratio of 0.7 with 90% power and a 1-sided alpha of 0.025; randomization was stratified by disease site (intrahepatic cholangiocarcinoma [CCA] vs gallbladder adenocarcinoma [GBC] vs extrahepatic CCA), disease stage (locally advanced vs metastatic), and Zubrod PS 0 vs 1. Results: Of 441 eligible pts randomized, 55% were female. 67% of patients had intrahepatic CCA, 16% had GBC and 17% had extrahepatic CCA. Most pts had metastases (73%). Median OS with GAP vs. GC was 14 vs. 12.7 mo respectively (HR 0.93, 95% CI 0.74-1.19, p=0.58), ORR (confirmed and unconfirmed) 34% vs 25% (p=0.11) and median PFS 8.2 vs 6.4 mo (HR 0.92, 95% CI 0.72-1.16, p=0.47), respectively. Grade 3 and 4 treatment related adverse events (TRAEs) in ≥10% of pts for GAP and GC were anemia, neutropenia, and thrombocytopenia. GAP had more ≥ grade 3 hematologic AEs compared to the GC arm (60% vs. 45%, p=0.003). Discontinuation due to toxicity was at 24% vs 19% (p=0.26) with GAP vs GC. In exploratory subset analyses, GAP vs GC improved OS in pts with locally advanced disease (medians 19.2 vs 13.7 mo; HR 0.67, 95% CI 0.42-1.06, p=0.09) and in GBC pts (medians 17.0 vs 9.3 mo; HR 0.74, 95% CI 0.41-1.35, p=0.33). ORR for GAP vs GC in GBC was 50% vs 24% (p=0.09) and for locally advanced disease 28 vs 21% p=0.74. Conclusions: SWOG 1815 did not result in a statistically significant improvement in median OS with GAP vs. GC. The GAP regimen had higher rates of TRAEs without a statistically significant difference in discontinuation rates. Pts with locally advanced disease and GBC may benefit from the use of GAP. Further analyses are ongoing to understand potential benefit of GAP in subsets of BTC pts. Funding: NIH/National Cancer Institute grants CA180888, CA180819, CA180820, CA180821, and CA180868; and in part by Celgene Corporation, Summit, NJ (subsidiary of Bristol Myer Squibb). Clinical trial information: NCT#03768414 .

Purpose:Recent studies demonstrate the success of Kasai portoenterostomy for biliary atresia (BA) is linearly related to infant age at time of Kasai. We sought to review the feasibility and safety of laparoscopic needle micropuncture cholangiogram with concurrent core liver biopsy (if needed) for expedited exclusion of BA in patients with direct conjugated hyperbilirubinemia.Methods:Expedited laparoscopic cholangiogram and liver biopsy were instituted at our facility for infants with direct hyperbilirubinemia for whom clinical exam and laboratory workup failed to diagnose. A retrospective chart review was performed in infants <1 year with hyperbilirubinemia from 2016 to 2021. Demographics, preoperative evaluation, procedure details, and complications were reviewed.Results:Two hundred ninety‐seven infants with unspecified jaundice were identified, of which, 86 (29%) required liver biopsy. Forty‐seven percutaneous liver biopsies were obtained including 8 (17%) in whom BA could not be excluded. Laparoscopic cholangiogram was attempted in 47 infants following basic workup; BA was diagnosed in 22 infants (47%) of which 3 were <18 days old. Biliary patency was demonstrated laparoscopically in 22 of 25 (88%); 3 (12%) required conversion to open cholangiogram. Infants with percutaneous liver biopsy had an average delay of 3 days (range: 2–36) to cholangiogram. Preoperative studies and liver biopsy alone did not reliably exclude the diagnosis of BA.Conclusion:Laparoscopic cholangiogram with liver biopsy is a safe procedure resulting in the confirmation or exclusion of BA in infants. Forty‐seven percent of infants who underwent laparoscopic cholangiogram were found to have BA; those who were surgical candidates underwent Kasai during the same operation.

Background Biliopancreatic diversion with duodenal switch (BPD-DS) is the most effective and durable metabolic and bariatric surgery to achieve a target weight loss. However, many surgeons are hesitant to adopt BPD-DS due to a lack of training, technical complexity, and long-term nutrition deficiencies. This meta-analysis aimed to investigate long-term nutrition outcomes after primary BPD-DS in the management of obesity. Methods Cochrane, Embase, PubMed, Scopus, and Web of Science were searched for articles from their inception to February 2023 by 2 independent reviewers using the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) system. The review was registered prospectively with PROSPERO (CRD42023391316). Results From 834 studies screened, 8 studies met the eligibility criteria, with a total of 3443 patients with obesity undergoing primary BPD-DS. At long-term follow-up (≥5 years), 25.4% of patients had vitamin A deficiency (95% CI: -.012, .520, I 2 = 94%), and 57.3% had vitamin D deficiency (95% CI: .059, 1.086, I 2 = 86%). Calcium deficiency was observed in 125 patients (22.2%, 95% CI: .061, .383, I 2 = 97%), and 69.7% had an abnormal parathyroid hormone level (95% CI: .548, .847, I 2 = 78%). Ferritin level was abnormal in 30 patients (29.0%, 95% CI: .099, .481, I 2 = 79%). Conclusions Despite displaying comparable nutrition-related outcomes to mid-term follow-up, our study demonstrated that BPD-DS could result in a high level of long-term nutrition deficiency after BPD-DS for selected patients. However, further randomized controlled studies with standardized supplementation regimens and improvement in compliance are necessary to evaluate and prevent long-term nutritional deficiencies after BPD-DS.

Abstract BACKGROUND The Response Assessment in Neuro-Oncology (RANO) criteria for high-grade gliomas (RANO-HGG) and low-grade gliomas (RANO-LGG) were developed to improve reliability of response assessment in glioma trials. Over time some limitations of these criteria were identified, and uncertainty emerged regarding integrating features of the modified RANO (mRANO) or the immunotherapy RANO (iRANO) criteria. MATERIAL AND METHODS Informed by data from a cohort of glioblastoma patients and other evaluations of RANO criteria that allowed evaluation of features of the different criteria, the RANO working group developed updates to the RANO criteria (RANO 2.0). RESULTS Based on the 2021 WHO classification of gliomas, we recommend a standard set of criteria for both high and low-grade gliomas, to be used for all trials regardless of the treatment modalities being evaluated. In the newly diagnosed setting, the post-radiotherapy MRI, rather than the post-surgical MRI, will be used as the baseline for future comparison. Since the incidence of pseudoprogression is high in the 12 weeks following radiotherapy, continuation of treatment and confirmation of progression during this period with a repeat MRI, or histopathologic evidence of unequivocal recurrent tumor, is required to define tumor progression. However, confirmation scans are not mandatory after this period nor for recurrent tumors. For treatments with a high likelihood of pseudoprogression, mandatory confirmation of progression with a repeat MRI is highly recommended. The primary measurement remains the maximum cross-sectional area of tumor (2-dimensional) but volumetric measurements are an option. For IDH-wildtype glioblastoma, the non-enhancing disease will no longer be evaluated. In IDH-mutated tumors with a significant non-enhancing component, clinical trials may require evaluating both the enhancing and non-enhancing tumor components for response assessment. CONCLUSION These criteria represent a work in progress that will hopefully improve the assessment of response in glioma trials. Future updates will incorporate novel developments, advanced imaging techniques, and endpoints as they become validated.

Study Design. Retrospective cohort study. Objective. Hounsfield units (HUs) are known to correlate with clinical outcomes, but no study has evaluated how they correlate with biomechanical computed tomography (BCT) and dual-energy x-ray absorptiometry (DXA) measurements. Summary of Background. Low bone mineral density (BMD) represents a major risk factor for fracture and poor outcomes following spine surgery. DXA can provide regional BMD measurements but has limitations. Opportunistic HUs provide targeted BMD estimates; however, they are not formally accepted for diagnosing osteoporosis in current guidelines. More recently, BCT analysis has emerged as a new modality endorsed by the International Society for Clinical Densitometry for assessing bone strength. Methods. Consecutive cases from 2017 to 2022 at a single institution were reviewed for patients who underwent BCT in the thoracolumbar spine. BCT-measured vertebral strength, trabecular BMD, and the corresponding American College of Radiology Classification were recorded. DXA studies within three months of the BCT were reviewed. Pearson Correlation Coefficients were calculated, and receiver-operating characteristic curves were constructed to assess the predictive capacity of HUs. Threshold analysis was performed to identify optimal HU values for identifying osteoporosis and low BMD. Results. Correlation analysis of 114 cases revealed a strong relationship between HUs and BCT vertebral strength (r=0.69; P<0.0001; R 2=0.47) and trabecular BMD (r=0.76; P<0.0001; R 2=0.58). However, DXA poorly correlated with opportunistic HUs and BCT measurements. HUs accurately predicted osteoporosis and low BMD (Osteoporosis: C=0.95, 95% CI 0.89–1.00; Low BMD: C=0.87, 95% CI 0.79–0.96). Threshold analysis revealed that 106 and 122 HUs represent optimal thresholds for detecting osteoporosis and low BMD. Conclusion. Opportunistic HUs strongly correlated with BCT-based measures, while neither correlated strongly with DXA-based BMD measures in the thoracolumbar spine. HUs are easy to perform at no additional cost and provide accurate BMD estimates at noninstrumented vertebral levels across all American College of Radiology-designated BMD categories.

AbstractBackgroundThe feasibility of oral dark contrast media is under exploration in abdominal computed tomography (CT) applications. One of the experimental contrast media in this class is dark borosilicate contrast media (DBCM), which has a CT attenuation lower than that of intra‐abdominal fat.PurposeTo evaluate the performances of DBCM using single‐ and multi‐energy CT imaging on a clinical photon‐counting‐detector CT (PCD‐CT).MethodsFive vials, three with iodinated contrast agent (5, 10, and 20 mg/mL; Omnipaque 350) and two with DBCM (6% and 12%; Nextrast, Inc.), and one solid‐water rod (neutral contrast agent) were inserted into two multi‐energy CT phantoms, and scanned on a clinical PCD‐CT system (NAEOTOM Alpha) at 90, 120, 140, Sn100, and Sn140 kV (Sn: tin filter) in multi‐energy mode. CARE keV IQ level was 180 (CTDIvol: 3.0 and 12.0 mGy for the small and large phantoms, respectively). Low‐energy threshold images were reconstructed with a quantitative kernel (Qr40, iterative reconstruction strength 2) and slice thickness/increment of 2.0/2.0 mm. Virtual monoenergetic images (VMIs) were reconstructed from 40 to 140 keV at 10 keV increments. On all images, average CT numbers for each vial/rod were measured using circular region‐of‐interests and averaged over eight slices. The contrast‐to‐noise ratio (CNR) of iodine (5 mg/mL) against DBCM was calculated and plotted against tube potential and VMI energy level, and compared to the CNR of iodine against water. Similar analyses were performed on iodine maps and VNC images derived from the multi‐energy scan at 120 kV.ResultsWith increasing kV or VMI keV, the negative HU of DBCM decreased only slightly, whereas the positive HU of iodine decreased across all contrast concentrations and phantom sizes. CT numbers for DBCM decreased from −178.5 ± 9.6 to −194.4 ± 6.3 HU (small phantom) and from −181.7 ± 15.7 to −192.1 ± 11.9 HU (large phantom) for DBCM‐12% from 90 to Sn140 kV; on VMIs, the CT numbers for DBCM decreased minimally from −147.1 ± 15.7 to −185.1 ± 9.2 HU (small phantom) and −158.8 ± 28.6 to −188.9 ± 14.7 HU (large phantom) from 40 to 70 keV, but remained stable from 80 to 140 keV. The highest iodine CNR against DBCM in low‐energy threshold images was seen at 90 or Sn140 kV for the small phantom, whereas all CNR values from low‐energy threshold images for the large phantom were comparable. The CNR values of iodine against DBCM computed on VMIs were highest at 40 or 70 keV depending on iodine and DBCM concentrations. The CNR values of iodine against DBCM were consistently higher than iodine to water (up to 460% higher dependent on energy level). Further, the CNR of iodine compared to DBCM is less affected by VMI energy level than the identical comparison between iodine and water: CNR values at 140 keV were reduced by 46.6% (small phantom) or 42.6% (large phantom) compared to 40 keV; CNR values for iodine compared to water were reduced by 86.3% and 83.8% for similar phantom sizes, respectively. Compared to 70 keV VMI, the iodine CNR against DBCM was 13%–79% lower on iodine maps and VNC.ConclusionsWhen evaluated at different tube potentials and VMI energy levels using a clinical PCD‐CT system, DBCM showed consistently higher CNR compared to iodine versus water (a neutral contrast).

Abstract Background Sinonasal neoplasms, whether benign and malignant, pose a significant challenge to clinicians and represent a model area for multidisciplinary collaboration in order to optimize patient care. The International Consensus Statement on Allergy and Rhinology: Sinonasal Tumors (ICSNT) aims to summarize the best available evidence and presents 48 thematic and histopathology‐based topics spanning the field. Methods In accordance with prior International Consensus Statement on Allergy and Rhinology documents, ICSNT assigned each topic as an Evidence‐Based Review with Recommendations, Evidence‐Based Review, and Literature Review based on the level of evidence. An international group of multidisciplinary author teams were assembled for the topic reviews using the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses format, and completed sections underwent a thorough and iterative consensus‐building process. The final document underwent rigorous synthesis and review prior to publication. Results The ICSNT document consists of four major sections: general principles, benign neoplasms and lesions, malignant neoplasms, and quality of life and surveillance. It covers 48 conceptual and/or histopathology‐based topics relevant to sinonasal neoplasms and masses. Topics with a high level of evidence provided specific recommendations, while other areas summarized the current state of evidence. A final section highlights research opportunities and future directions, contributing to advancing knowledge and community intervention. Conclusion As an embodiment of the multidisciplinary and collaborative model of care in sinonasal neoplasms and masses, ICSNT was designed as a comprehensive, international, and multidisciplinary collaborative endeavor. Its primary objective is to summarize the existing evidence in the field of sinonasal neoplasms and masses.

Current methods for biomarker discovery and target identification in immuno-oncology rely on static snapshots of tumor immunity. To thoroughly characterize the temporal nature of antitumor immune responses, we developed a 34-parameter spectral flow cytometry panel and performed high-throughput analyses in critical contexts. We leveraged two distinct preclinical models that recapitulate cancer immunoediting (NPK-C1) and immune checkpoint blockade (ICB) response (MC38), respectively, and profiled multiple relevant tissues at and around key inflection points of immune surveillance and escape and/or ICB response. Machine learning-driven data analysis revealed a pattern of KLRG1 expression that uniquely identified intratumoral effector CD4 T cell populations that constitutively associate with tumor burden across tumor models, and are lost in tumors undergoing regression in response to ICB. Similarly, a Helios-KLRG1+ subset of tumor-infiltrating regulatory T cells was associated with tumor progression from immune equilibrium to escape and was also lost in tumors responding to ICB. Validation studies confirmed KLRG1 signatures in human tumor-infiltrating CD4 T cells associate with disease progression in renal cancer. These findings nominate KLRG1+ CD4 T cell populations as subsets for further investigation in cancer immunity and demonstrate the utility of longitudinal spectral flow profiling as an engine of dynamic biomarker discovery.

SummaryBackgroundMedication use has been implicated in the development of microscopic colitis (MC). However, studies have demonstrated inconsistent findings and there exist variations in design.AimTo measure the association between medication use and MC.MethodsPatients who underwent a colonoscopy over a 10‐year period at two academic medical centres (Columbia University Medical Centre and Mayo Clinic) were identified. Cases were patients with biopsy‐proven MC and controls were patients who underwent colonoscopy for evaluation of diarrhoea with biopsies negative for MC. Cases were matched by age, gender and calendar period with up to two controls. Demographics, medication use, smoking history and coeliac disease status were collected. Conditional logistic regression was used with and without adjustment for smoking.ResultsA total of 344 patients with MC were matched to 668 controls. After adjusting for smoking, there was an inverse association between MC and use of proton pump inhibitors (PPIs) (OR 0.64; 95% CI 0.47‐0.87), H2 blockers (OR 0.46; 95% CI 0.24‐0.88) and oral diabetes medications (OR 0.47; 95% CI 0.27‐0.81). There was a positive association with nonsteroidal anti‐inflammatory drug (NSAID) use and MC (OR 1.63; 95% CI 1.12‐2.38).ConclusionsNSAID use was associated with MC, while use of PPIs, H2 blockers and oral diabetes medications were inversely related to MC. Our use of a control group with diarrhoea, as opposed to healthy controls, may have contributed to these inverse associations. Future studies of drug‐induced microscopic colitis should include control groups with diarrhoea, and not only healthy controls.