Biliary Tract Tumors Research Articles

Estimating Microvascular Invasion in Patients with Resectable Multinodular Hepatocellular Carcinoma by Using Preoperative Contrast-Enhanced MRI: Establishment and Validation of a Risk Score.

To determine the preoperative clinicoradiological factors to predict microvascular invasion (MVI) in patients with resectable multinodular hepatocellular carcinoma (mHCC), and further to establish and validate a stratified risk scoring system. Two hundred and seventy-three patients with pathologically confirmed mHCC (≥2 lesions) without major vascular invasion and biliary tract tumor thrombosis, who underwent preoperative contrast-enhanced MRI and hepatectomy, were consecutively enrolled (training/validation cohort=193/80). Preoperative clinicoradiological variables were collected and analyzed. The multivariable logistic regression was performed to determine the independent predictors of MVI and create a risk score system. The C-index, calibration curve and decision curve were used to evaluate the performance of the risk score. A risk score-based prognostic stratification system was performed in mHCC patients. The risk score system was further verified in the validation cohort. AFP > 400 ng/mL, presence of satellite nodule, mosaic architecture and increased total tumor diameter were independent predictors of MVI while fat in mass was an independent protective factor of MVI. The risk score yielded satisfactory C-index values (training/validation cohort: 0.777/0.758) and fitted well in calibration curves. Decision curve analysis further confirmed its clinical utility. Based on the risk score, mHCC patients were stratified into high-/low-MVI-risk subgroups with significantly different recurrence-free survival (both P < 0.001). The presented risk score incorporating clinicoradiological parameters could stratify mHCC patients into high-risk and low-risk subgroups and predict prognosis in patients with resectable mHCC.

Efficacy and safety of trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2-expressing solid tumors: DESTINY-PanTumor02 (DP-02) interim results.

LBA3000 Background: T-DXd is an antibody drug conjugate targeting HER2 and is approved in HER2-expressing breast (BC) and gastric (GC) cancers. HER2 expression is prevalent in other solid tumors. The efficacy of current treatments (Tx) in these populations, including studies with HER2-directed Tx, is modest, revealing a significant unmet medical need. Clinically meaningful activity of T-DXd was seen in HER2-expressing tumors in a phase 1 study (NCT02564900). Methods: DP-02 (NCT04482309) is an open-label phase 2 study of T-DXd 5.4 mg/kg q3w in pts with HER2-expressing (immunohistochemistry [IHC] 3+ or IHC 2+ by local or central testing) locally advanced or metastatic disease that progressed after ≥1 systemic Tx or that has no Tx options. Cohorts with biliary tract (BTC), bladder (URO), cervical (CC), endometrial (EC), ovarian (OC), pancreatic (PC), or other tumors (excluding BC, GC, colorectal cancer, and non-small cell lung cancer) were enrolled. Efficacy and safety were analyzed in all pts who received ≥1 dose of T-DXd. The primary endpoint was investigator-assessed confirmed objective response rate (ORR). Secondary endpoints included duration of response (DOR), disease control rate, progression-free and overall survival, and safety. Results: At data cutoff (16 Nov 2022; median follow-up, 9.7 mo), 267 pts had been treated (median, 2 prior lines of Tx [range, 0-13]); 75 pts were IHC 3+ and 125 were IHC 2+ by central testing. In all 267 pts, the ORR was 37.1% and median DOR (mDOR) was 11.8 mo; in pts with IHC 3+ expression, the ORR was 61.3% and mDOR was 22.1 mo. ORR per cohort is shown in all pts and those with centrally confirmed HER2 IHC 3+ or IHC 2+ expression. Grade (G) ≥3 adverse events (AEs) occurred in 58.4% of pts; 11.6% discontinued Tx due to AEs. Adjudicated drug-related interstitial lung disease/pneumonitis occurred in 18 pts (6.7% [G1, n=6; G2, n=11; G5, n=1]). Conclusions: This is the first tumor-agnostic global study of T-DXd in a broad range of HER2-expressing solid tumors. T-DXd showed encouraging ORR, particularly in pts with IHC 3+ expression, durable clinical benefit, and a manageable safety profile in this heavily pretreated population. These interim results show T-DXd to be a potential new Tx option for pts with HER2-expressing solid tumors. Clinical trial information: NCT04482309 . [Table: see text]

Genomic profiles of chromosome remodeling pathway and their correlation with TMB, MSI, PD-L1, and immune microenvironment in biliary tract tumors.

e16181 Background: Immunotherapy combined with chemotherapy has become a promising first-line treatment for biliary tract tumor (BTC) patients. A previous clinical trial with a small sample size revealed that impaired functions of chromatin remodeling genes might be a potential predictive biomarker of combined immunotherapy for BTC. However, genomic profiles of chromosome remodeling pathway and their correlation with tumor mutation burden (TMB), microsatellite instability (MSI), programmed death ligand-1 (PD-L1) and immune microenvironment in Chinese BTC patients remain unknown. Methods: A total of 2031 BTC patients (cholangiocarcinoma [CCA], N=1476; gallbladder carcinoma [GBC], N=555) were included in this study, and their tumor tissue samples were subject to next generation sequencing using a 733-gene panel. Multiple immunofluorescence using for immune microenvironment related markers (including PD-1, PD-L1, CD8, CD68, CD163, CD3, CD4, CD20, CD56 and FoxP3) detection was conducted in 49 patients. Prognostic survival data were obtained from two clinical sequencing cohorts (CCA: ICGC-2017, N=417; GBC: MSK-2022, N=233) and were used to explore the association between chromatin remodeling genes mutation and prognosis. Results: In total, 57.9% (1175/2031) of BTC patients harbored alternations in genes involved in chromatin remodeling pathway and the top three alteration frequency somatic genes were ARID1A (19%), KMT2C (11%), ARID2/KMT2D/PBRM1 (8% each), respectively. The commonly alternation types were missense (48%), frameshift indel (25%) and nonsense (17%), respectively. The TMB level of altered group was significantly higher than wild group (median TMB, mutant-type vs. wild-type = 6.145 vs. 3.352 Muts/Mb, P&lt;0.0001), but no significant difference was found in the PD-L1 expression level between the two groups. A total of 43 patients were identified as MSI-high, all of whom harbored alternations in genes involved in chromatin remodeling pathway. Compared with the wild group, the infiltration level of CD20+ B cells in tumor parenchyma was significantly higher in the altered group. Furthermore, there was no difference in overall survival (OS) between altered group and wild group (median OS, 18.99 vs. 20.97 months; HR=1.164 [95%CI: 0.9048-1.498], P=0.2360) in two clinical sequencing cohorts without immunotherapy. Conclusions: The results revealed the molecular basis of chromosome remodeling genes as the predictive biomarker of combined immunotherapy for BTC and exclude its effect on prognosis.

A phase I/II dose escalation and expansion trial to evaluate safety and preliminary efficacy of BNT141 in patients with claudin-18.2-positive solid tumors.

TPS2670 Background: Claudin-18.2 (CLDN18.2), whose expression is normally restricted to short-lived gastric epithelial cells, is ectopically expressed in tumors with unmet needs such as gastric, gastroesophageal junction (GEJ), pancreatic, ovarian, and biliary tract tumors. CLDN18.2 has thus emerged as a promising target for therapeutic antibody development. BNT141 is a novel RNA-based therapeutic that comprises two pseudouridine-modified mRNAs encapsulated in lipid nanoparticles. Upon intravenous injection, BNT141 is preferentially taken up by the liver where RNAs are translated and released into the circulation as fully assembled anti-CLDN18.2 antibodies. The resulting antibody is sequence identical to IMAB362, a CLDN18.2-targeted antibody that provided clinical benefit as an add-on to chemotherapy in the Phase III SPOTLIGHT trial (Shitara et al. J Clin Oncol. 2023). RNA-encoded antibodies can be developed more rapidly compared with recombinant antibodies and have the potential for favorable PK/PD properties and improved tolerability. Methods: This is a Phase I/II, open-label, multisite, dose escalation and expansion trial to examine safety, efficacy, and PK/PD of BNT141 in patients with CLDN18.2+ tumors (NCT04683939). The trial comprises 3 parts: dose escalation with BNT141 as monotherapy, dose escalation with BNT141 in combination with nab-paclitaxel and gemcitabine, and dose expansion. For monotherapy dose escalation, patients with CLDN18.2+ gastric, GEJ, pancreatic, mucinous ovarian, and biliary tract cancers who have exhausted or are ineligible for the current standard of care are eligible. CLDN18.2 positivity is defined as intermediate/strong staining intensity in ≥50% of tumor cells evaluated using a validated immunohistochemistry assay. Doses of BNT141 are escalated in up to 8 planned dose levels (DLs) until the maximum tolerated dose (MTD) is reached. For combination dose escalation, patients with advanced CLDN18.2+ pancreatic adenocarcinoma or cholangiocarcinoma who are eligible for treatment with nab-paclitaxel/gemcitabine will be included. Combination therapy will start at the first safe DL where the target antibody concentration is reached during monotherapy. Combination dose escalation will continue in parallel with the monotherapy part and will define the recommended Phase II dose (RP2D). For both parts, up to 10 additional patients may be enrolled at the MTD level to collect further safety and PK/PD data. For dose expansion, 2 cohorts of patients with CLDN18.2+ pancreatic adenocarcinoma or cholangiocarcinoma will receive combination therapy (nab-paclitaxel/gemcitabine) together with BNT141 at the defined RP2D. The study was initiated in January 2022 and recruitment is ongoing in the USA and Canada. Sites in Spain, Portugal, Germany, Denmark, Netherlands and the UK will be opened in 2023. Clinical trial information: NCT04683939 .

Correlation between MSI, TMB, and TGFBR2 gene mutation in solid tumors.

e14558 Background: TGFBR2 encodes a receptor kinase which signals to downstream effectors in the TGF-ß signaling pathway. Recent research has shown that truncation mutations of TGFBR2 in gastric cancer with high tumor mutational burden. However, the relationship remains unclear in other solid tumors. Methods: We retrospectively analyzed the TGFBR2 mutations of 19370 Chinese patients with pan-cancer during 2019-2022 (Simcere Diagnosis, Nanjing, China) Next-generation sequencing (NGS) assessed somatic mutations in tumor tissue. We figured out TGFBR2 mutation frequency, TMB and MSI in TGFBR2-mutant, TGFBR2 wild-type. Results: We have detected TGFBR2 mutants in 536 (2.8%) samples. The top 5 frequent cancers were colorectal cancer (132, 24.7%), lung cancer (118, 22%), gastric cancer (78, 14.5%), biliary tract tumors(52, 9.7%) liver cancer (33, 6.2%).TGFBR2 variants included missense/indel/insert (238, 44.4%), truncation (219, 40.9%), splicing site variant (23, 4.3%), and CNV (33, 6.2%).The inactive variants include missense, which occurs in the TGFBR2 serine/threonine kinase domain, truncation and splicing site variant. However, truncation was the most common type, recurring in a few hot spots (p.K153Sfs*35, p.K153Afs*3, p.R520* ). And we found that the TMB and MSI in the TGFBR2 mutation group was significantly higher than that in the TGFBR2 wild-type group [TMB-H (TMB ≥10 musts/Mb): TGFBR2-MUT vs TGFBR2-WT, 41.2% vs 9.5%, p &lt; 0.01; MSI-H: TGFBR2-MUT vsTGFBR2-WT, 27.4% vs1.7% p &lt; 0.01]. In the TGFBR2 mutation group, It was also observed that TMB and MSI in the TGFBR2 truncation or splicing site mutant (INACT) group was significantly higher than that in the other mutant types (VUS) group [TMB-H (TMB ≥10 musts/Mb): TGFBR2-INACT vs TGFBR2-VUS, 51.0% vs 27.9%, p &lt; 0.01; MSI-H: TGFBR2-INACT vs TGFBR2-VUS 39.4% vs 10.6% p &lt; 0.01]. And then, we separately analyzed the correlation between MSI, TMB and TGFBR2 gene mutation in the top 5 frequent cancers. Over 60% of patients with TGFBR2 mutations in colorectal cancers have high TMB and MSI values [TMB-H (TMB ≥10 musts/Mb): TGFBR2-MUT vs TGFBR2-WT, 71.3% vs 12.8%, p &lt; 0.01; MSI-H: TGFBR2-MUT vs TGFBR2-WT, 61.2% vs 3.0% p &lt; 0.01]. Conclusions: We analyzed the distribution of TGFBR2 mutants in Chinese patients with solid tumors. Our data showed that TGFBR2 mutant was significantly associated with TMB-H and MSI-H, and this may be a potential molecular marker of immunotherapy. And studies have shown that the combination of TGF-β inhibitors and immune checkpoint inhibitors can increase the killing effect of T cells on tumors. In short, detection of TGFBR2 mutation has certain clinical significance.

The landscape of ATM alteration in Chinese solid tumor patients.

e15147 Background: The Ataxia-telangiectasia mutated (ATM) gene is an oncosuppressor, which plays an important role in the repair of DNA double-strand breaks (DSBs). The mutation profiles of ATM gene in Chinese solid tumor patients can help understand pathogenesis, prognosis, and identify targets for therapy. Methods: Using commercial NGS assays, we retrospectively analyzed genomic DNA alterations in normal-paired samples from 1351 patients with malignancies from January 2021 to October 2022, and alterations including single base substitution, short and long insertion/deletions, copy number variations, gene fusions and rearrangements. Results: ATM gene was altered in 6.8% (92 of 1351) of all solid tumors. The frequency of ATM variations was assessed in multiple cancer types, including non-small cell lung cancer 22% (35/159), endometrial carcinoma 15% (2/13), biliary tract tumor 12.1% (7/58), gastric cancer 10.7% (3/28), prostatic cancer 8.3% (1/12), breast cancer 6.7% (2/30), colorectal cancer 6.5% (11/168), thyroid cancer 6.2% (5/80), cervical carcinoma 5.7% (2/35), prostatic cancer 3.9% (2/51), liver cancer 3% (2/66). A total 102 genetic alterations were identified in 92 patients, including 70 missense mutations (69%), 14 nonsense (14%), 9 splicing (9%), 3 frameshift (3%), 2 deletion (2%), 2 copy number variation (2%). Among these patients, 2 had pathogenic germline ATM heterozygous mutations, including one lung adenocarcinoma and one pancreatic cancer. Furthermore, in our cohort, ATM mutation carriers also owned other actionable mutation, the most frequent one was TP53 (41%), followed by APC (29%), KRAS (23%), MLL3 (22%) and BRCA2 (20%). Conclusions: Our findings indicate that ATM alterations are widely mutated in Chinese multiple cancer types, with specific mutations differing largely among different tumor types. ATM alterations warrant further investigation as predictive biomarkers of response to PARP inhibitors or platinum-based therapy.

Impact on costs and outcomes of multi-gene panel testing for advanced solid malignancies: A cost consequence analysis using linked administrative data.

6650 Background: To date, economic analyses of tissue-based next generation sequencing genomic profiling (NGS) have required models with multiple assumptions, with little real-world evidence on overall survival (OS), clinical trial enrollment or end-of-life (EOL) quality of care. The OCTANE clinical trial (NCT02906943) is a prospective study evaluating the role of NGS for advanced solid tumors in Ontario, Canada. We performed a cost consequence analysis of OCTANE. Methods: We undertook a longitudinal, propensity score-matched retrospective cohort study using linked administrative data. OCTANE patients (pts) at Princess Margaret Cancer Centre from August 2016 until March 2019 undergoing NGS panel testing (555 or 163-gene panels) were matched with contemporary controls from across Ontario not enrolled in OCTANE. Patients were matched according to 19 variables including age, sex, place of residence, tumor site, symptom burden, income quintile, comorbidities and prior lines of systemic therapy. Primary outcomes were mean per capita health care costs (2019 Canadian dollars [CAD]) from the public payer’s perspective, OS, clinical trial enrollment and EOL quality metrics. Full 2-year follow-up data was available. Sensitivity analyses considered alternative matched cohort specifications. Results: There were 782 OCTANE pts with 782 matched controls. Variables were balanced after matching (standardized difference [std. diff.]&lt;0.10). Most common tumor sites were: Ovary (30.4%), endometrium (15.0%) breast (12.3%) and colon (8.6%). OCTANE pts had higher mean healthcare costs than controls ($79,702 vs. $59,550), mainly due to costs of oncology visits ($33,165 vs. $26,197), outpatient clinic visits ($8,696 vs. $5,114) and emergency visits ($1,723 vs. $1,373) (all p&lt;0.05). Publicly funded drug costs were less for OCTANE pts ($20,015 vs. $24,465). Overall, OCTANE enrollment was not associated with improved OS (restricted mean survival time (RMST) [standard error]: 1.50 (±0.03) vs. 1.44 (±0.03) years, log-rank p=0.153), but OCTANE was associated with longer OS in ovarian cancer (RMST: 1.69 (±0.05) vs. 1.45 (±0.06) years, p=0.011) and biliary tract tumors (RMST: 1.16 (±0.13) vs. 0.80 (±0.11) years, p=0.02). Importantly, OCTANE correlated with increased clinical trial enrollment (25.5% vs. 9.5%, p&lt;0.001) and better EOL quality due to fewer deaths in hospital (10.2% vs 16.4%, p=0.003). Results were robust in sensitivity analysis. Conclusions: There was an increase in healthcare costs associated with NGS testing for advanced cancers. The impact on OS was not significant in the overall population, but varied across tumor types. OCTANE was associated with greater trial enrollment, lower publicly funded drug costs and fewer in hospital deaths suggesting important considerations in determining the value of NGS for advanced cancers. Clinical trial information: NCT02906943 .

The impact of anti-EGFR therapy when added to first-line standard platinum-gemcitabine chemotherapy in advanced biliary tract cancers: A meta-analysis of randomized studies.

e16109 Background: Biliary tract cancers (BTCs) represent the second-most common primary liver cancers. They are a heterogeneous group of tumors that include Intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, gallbladder adenocarcinoma, and ampullary carcinoma. BTCs are usually diagnosed in an advanced stage and carry a poor prognosis. A better understanding of cancer biology has led to advances in targeted treatments in other cancers but remains an unmet need in BTCs. We conducted this meta-analysis to evaluate the efficacy of anti-EGFR therapy when added to the standard platinum-gemcitabine chemotherapy as first-line in patients with advanced BTCs. Methods: A review of the medical literature was conducted using online databases. Inclusion criteria consisted of English language, diagnosis of biliary tract tumors, randomized studies of first-line platinum-gemcitabine with and without anti-EGFR therapies, and studies that reported overall (OS) and progression free survival (PFS). A meta-analysis using the fixed effects and random effects models was conducted. Results: Four randomized studies with a total of 569 patients were included. Three studies were randomized phase 2 and one was randomized phase 3. Three studies used oxaliplatin and one used cisplatin in addition to gemcitabine as the standard combination. Panitumumab was used in two studies while cetuximab and erlotinib were used in one study each. The addition of anti-EGFR agent to first-line platinum-gemcitabine in advanced BTC resulted in a superior OS (HR = 0.72, 95%CI 0.61-0.85) and PFS (HR = 0.76, 95%CI 0.63-0.92). When the analysis was restricted to anti-EGFR monoclonal antibodies, their PFS benefit persisted (HR = 0.72, 95%CI 0.55-0.95), but their OS benefit failed to reach statistical significance (HR = 0.83, 95%CI 0.65-1.07). Conclusions: This is the first meta-analysis to show the addition of anti-EGFR agents to the standard first-line platinum-gemcitabine chemotherapy improves OS and PFS in advanced BTC.

Investigation of the accuracy of magnetic resonance cholangiography and multi-slice spiral computed tomography in the diagnosis of cholangiocarcinoma.

Cholangiocarcinoma (CCA) is a common malignant biliary tract tumor in clinical practice. The detection rate of multi-slice spiral computed tomography (MSCT) with a diameter of 10 mm is low, and it is easy to be misdiagnosed and missed. In addition, patients who are allergic to iodized contrast media are not eligible for MSCT screening. However, magnetic resonance cholangiopancreatography (MRCP) is non-invasive, does not require contrast injection, scans quickly, and is simple to perform. MRCP has good development rate and the ability to recognize human pancreas and biliary tract. MRCP is also non-invasive, does not require contrast injection, has fast scanning speed, and is easy to operate. In addition, MRCP has a good development rate and the ability to recognize human pancreas and biliary tract. Therefore, this study sought to analyze the accuracy of MRCP and MSCT in the diagnosis of CCA. In this paper, 186 patients with highly suspected CCA admitted to the Second Affiliated Hospital of Soochow University from March 2020 to May 2022 were selected for MSCT and MRCP examination. We compared the diagnostic accuracy, sensitivity and specificity of MSCT and MRCP with pathological diagnosis and the detection rate of lesions with different diameters between MSCT and MRCP. Finally, the imaging features of MSCT and MRCP of CCA were analyzed. The results showed that (I) the diagnostic accuracy (95.70%), sensitivity (95.12%), and specificity (96.15%) of MRCP were higher than those of MSCT (69.89%, 60.98%, and 76.92%, respectively; P<0.05); (II) MSCT and MRCP were basically consistent with the datum (Kappa value =0.527, Kappa value =0.767, respectively); (III) the detection rate of lesions <0.5 cm in diameter of MRCP (32.05%) was higher than that of MSCT (14.00%; P<0.05); and (IV) the detection rates of lesions 0.5-1.0 cm (38.46%) and >1.0 cm (29.49%) in diameter of MRCP were lower those of MSCT (50.00%, and 36.00%, respectively; P>0.05). MRCP can provide relevant imaging feature information, improve the accuracy, sensitivity and specificity of the diagnosis of bile duct carcinoma, and has a high detection rate for small diameter lesions, which has good reference, promotion and reference value.

Bile detection of squamous cell carcinoma antigen (SCCA) in extrahepatic cholangiocarcinoma.

Cholangiocarcinoma (CCA) is a rare biliary tract tumor with poor prognosis that often is challenging to diagnose and the majority of patients present with advanced stage. Squamous cell carcinoma antigen 1 (SCCA1) overexpression has been found in different tumors associated with poor prognosis and chemoresistance. To assess the presence and possible prognostic role of SCCA1/2 isoforms in bile and serum of patients with CCA. Forty seven surgical patients (36 with CCA and 11 with benign diseases) were prospectively included in the study. Serum and bile specimens were collected at the time of surgery and free and IgM-complexed SCCA was quantified by ELISA (Xeptagen, srl). Free or IgM linked SCCA was rarely found in serum, while SCCA was detectable in bile samples of patients with CCA, especially in those with extrahepatic form (43% vs 17%, p=0.008), but not in controls. Despite similar tumor stage, these positive patients presented a trend toward a higher percentage of portal invasion (27% vs 15%) and of tumor recurrence than negative cases (62% vs 40%), although the difference was not statistically significant. These preliminary results indicate that bile testing for SCCA is a specific marker of extrahepatic CCA, with potential prognostic value.

A Two-Step Diagnostic Approach for NTRK Gene Fusion Detection in Biliary Tract and Pancreatic Adenocarcinomas.

It is of interest to determine the incidence and molecular characteristics of NTRK gene fusions in patients with bilio-pancreatic cancers, because of possible treatment with TRK inhibitors for advanced tumors. The aim of the present study was to apply the guidelines for NTRK testing algorithm to a series of patients with bilio-pancreatic cancers. Immunohistochemistry screening was applied on formalin-fixed paraffin-embedded archival blocks from surgical resections, biopsies, or cytological samples of biliary tract and pancreatic adenocarcinomas. The presence of at least a weak staining in rare tumor cells led to testing by 2 RNA-based NGS panels. For biliary tract tumors, 153 samples have been selected. A total of 140 samples were suitable to perform IHC, and 17 samples were IHC positive. RNA NGS testing of the 17 IHC-positive samples revealed a single NTRK3 gene fusion (ETV6(4)-NTRK3(14)) that was detected by both NGS panels. In this perihilar cholangiocarcinoma, IHC performed on a biopsy showed a weak focal cytoplasmic and nuclear staining. No other NTRK fusion was detected on the 16 other samples with both panels. Overall in the patients screened by IHC and confirmed by NGS, the percentage of NTRK fusions was 0.7%. For pancreatic cancers, 319 samples have been selected and 297 were suitable to perform IHC. Nineteen samples were IHC positive. No fusion was detected by NGS. NTRK gene fusions are rare in bilio-pancreatic cancers but testing is of high interest due to possible treatment with specific TRK inhibitors.

Risk factor analysis and construction of prediction models of gallbladder carcinoma in patients with gallstones.

Gallbladder carcinoma (GBC) is a biliary tract tumor with a high mortality rate. The objectives of this study were to explore the risk factors of GBC in patients with gallstones and to establish effective screening indicators. A total of 588 patients from medical centers in two different regions of China were included in this study and defined as the internal test samples and the external validation samples, respectively. We retrospectively reviewed the differences in clinicopathologic data of the internal test samples to find the independent risk factors that affect the occurrence of GBC. Then, we constructed three different combined predictive factors (CPFs) through the weighting method, integral system, and nomogram, respectively, and named them CPF-A, CPF-B, and CPF-C sequentially. Furthermore, we evaluated these indicators through calibration and DCA curves. The ROC curve was used to analyze their diagnostic efficiency. Finally, their diagnostic capabilities were validated in the external validation samples. In the internal test samples, the results showed that five factors, namely, age (RR = 3.077, 95% CI: 1.731-5.496), size of gallstones (RR = 13.732, 95% CI: 5.937-31.762), course of gallstones (RR = 2.438, 95% CI: 1.350-4.403), CEA (RR = 9.464, 95% CI: 3.394-26.392), and CA199 (RR = 9.605, 95% CI: 4.512-20.446), were independent risk factors for GBC in patients with gallstones. Then, we established three predictive indicators: CPF-A, CPF-B, and CPF-C. These models were further validated using bootstrapping with 1,000 repetitions. Calibration and decision curve analysis showed that the three models fit well. Meanwhile, multivariate analysis showed that CPF-B and CPF-C were independent risk factors for GBC in patients with gallstones. In addition, the validation results of the external validation samples are essentially consistent with the internal test samples. Age (≤58.5 vs. >58.5 years), size of gallstones (≤1.95 vs. >1.95cm), course of gallstones (≤10 vs. >10 years), CEA (≤5 vs. >5 ng/ml), and CA199 (≤37 vs. >37 U/ml) are independent risk factors for GBC in patients with gallstones. When positive indicators were ≥2 among the five independent risk factors or the score of the nomogram was >82.64, the risk of GBC was high in gallstone patients.

A case report of neuroendocrine tumor of extrahepatic biliary tract

A case report of neuroendocrine tumor of extrahepatic biliary tract

Treatment patterns and oncologic outcomes of carcinoma of the ampulla of vater in a reference hospital in a middle income country: A real-world–based study.

524 Background: Gallbladder and other biliary tract tumors account for 0.6 % of all cancers. There is scarce data of Ampullary cancers, but it is known as an extremely rare neoplasia accounting just for 0.2% of gastrointestinal cancers and 7% of periampullary tumors. Most frequent histology is adenocarcinoma being intestinal and pancreatobiliary subtypes conditioning prognosis and treatment. Current approaches include, but not limited to: neo/adyuvant, radiation and palliative therapy. Methods: We conducted a retrospective study in a referral specialized center in Mexico city. We included patients with histologically confirmed ampullary cancer treated between 2008 and 2022, stages I-IV. We evaluated the frequency of surgery, radiation therapy and chemotherapy. Also, we registered, first line, subsequent and maintenance therapy and as for radiation and chemoradiation. Chi square and student T test were used for between group comparisons. Overall survival was performed using the Kaplan Meier method. Results: We included 220 patients with a median age of 60.3 years (range 28-84), female 51.8%. The clinical stage distribution was I 10%, II 16.4%, III 41.3%, IV 32.3%. Performance status 0 (26.5%), 1 (44.5%), 2 (15.6%), 3 (10.4%), 4 (2.8%). Histologic Subtype Adenocarcinoma not otherwise specified 45.7%, Intestinal Adenocarcinoma 27.1%, Pancreatobiliary Adenocarcinoma 16.7%, Mix Intestinal-Pancreatobiliary 6.2%, Signet Ring Cell Adenocarcinoma 2.4%, Neuroendocrine 1.9%. Curative intend surgery in 169 patients was possible in 90%. Initial treatment received was Adjuvant 40.9%, Palliative 27.7%, Neoadjuvant 2.3% and Never Received any kind of treatment in 29.1%. Adjuvant Treatment was given to 94 patients. Among them Gemcitabine and Capecitabine was the election of treatment in 34% and 23.4 respectively. First line Treatment. Patients receiving first line treatment (110 patients) were candidates to Gemcitabine, XELOX, and Gemcitabine-Cisplatin in 30%, 13.6% and 12.7% according to physicians and 56% other line of treatment. Patients who progressed to first line received a second line in 19%. Most frequent second line of treatment was Capecitabine 61.9% and Gemcitabine 23.8%. Of the whole population Median Overall Survival was 30.68 months, Disease Free survival: 30.71 months and 8.0 months for progression free survival in first line. Conclusions: To our knowledge first real world based large volume study reporting treatment patterns and oncologic outcomes of a rare entity.

Adjuvant treatment for biliary tract tumors: lost in a maze?

1Department of Oncology – OncoHealth Institute, Fundación Jiménez Díaz University Hospital, Madrid Spain; Department of Medical Oncology, The Christie NHS Foundation, Manchester; Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom 2INSERM, Univ Rennes, Department of Medical Oncology, CLCC Eugène Marquis, COSS [(Chemistry Oncogenesis Stress Signaling)] – UMR_S 1242, F-35000 Rennes, France Correspondence Angela Lamarca, Department of Oncology – OncoHealth Institute, Fundación Jiménez Díaz University Hospital, Avda Reyes Catolicos 2, 28040, Madrid Spain. Email [email protected]

L-Fucose inhibits the progression of cholangiocarcinoma by causing microRNA-200b overexpression.

Cholangiocarcinoma (CCA) is a malignant biliary tract tumor with an extremely poor prognosis. There is an urgent demand to explore novel therapeutic strategies. L-fucose has been confirmed to participate in anti-inflammation and antitumor activities. However, the effect of L-fucose on the progression of CCA has not been well investigated. This study aimed to determine whether L-fucose induced the inhibition of CCA and its possible mechanism. The anti-growth activity was determined using Cell Counting Kit-8 assay, colony formation assays, Annexin V-fluorescein isothiocyanate/propidium iodide (FITC/PI) assay, and cell cycle analysis. The anti-metastasis activity was determined by wound healing, transwell, and invasion assays. The anti-angiogenesis activity was determined by tube formation and transwell assays. MicroRNAs that may be involved in the L-fucose-induced CCA inhibition was analyzed using bioinformatics methods. The preclinical therapeutic efficacy was mainly estimated by ultrasound in xenograft nude mouse models. Differences were analyzed via Student's t test or one-way analysis of variance. L-Fucose induced apoptosis and G0/G1 cell cycle arrest, inhibited cell epithelial-mesenchymal transition of CCA cells, and additionally inhibited tube formation of human umbilical vein endothelial cells (HUVECs) in a dose-dependent manner, leading to a decrease in cell proliferation, metastasis, and angiogenesis. Mechanistically, L-fucose induced microRNA-200b (miR-200b) upregulation, and mitogen-activated protein kinase 7 (MAPK7) downregulation was found to be targeted by miR-200b, with decreased cell proliferation and metastasis. Additionally, phosphorylated signal transducer and activator of transcription 3 was found to be downregulated after L-fucose treatment. Finally, in vivo experiments in CCA xenograft models also confirmed the antitumor properties of L-fucose. L-Fucose inhibited the progression of CCA via the miR-200b/MAPK7 and signal transducer and activator of transcription 3 signaling pathways.

The Optimal Treatment Approaches and Prognostic Factors In Elderly Patients with Advanced Stage Biliary Tract Tumors

The Optimal Treatment Approaches and Prognostic Factors In Elderly Patients with Advanced Stage Biliary Tract Tumors

Retracted: Therapeutic Effect and Prognosis of Biliary Tract Tumor Transformation.

[This retracts the article DOI: 10.1155/2022/9489003.].

HPB P41 Pitfalls in establishing a preoperative diagnosis; correlating the radiological and histopathological findings of suspected intraductal papillary neoplasm of the bile duct (IPNB)

Abstract Background Intraductal papillary neoplasm of the bile duct (IPNB) represents a cohort of uncommon biliary tract tumours. It is commonly unrecognised or misdiagnosed in cross sectional imaging of the liver. This rare tumour is of significant clinical importance as it serves as a pre-cursor lesion for Cholangiocarcinoma. The diagnostic work up of a patient with a suspected IPNB remains predominantly based on imaging and as of yet no consensus has been achieved regarding the optimal diagnostic algorithm. The aim of this study was to compare the radiological and clinico-pathological features of patients with confirmed or suspected IPNB managed in a single tertiary center. Methods Retrospective review of a departmental database of consecutive patients with suspected IPNB was performed. Clinical information regarding patient demographics, disease presentation, radiological imaging characteristics and histo-pathological features was analysed. Results Eighteen patients with suspected IPNB were noted, of which histological confirmation was present in eight cases (62%). The most frequent presentation of IPNB was of an incidental finding (50%). The diagnosis of IPNB was made following MRI in 63% of cases. Invasive adenocarcinoma was present in five patients (63%). In the remaining three patients, low grade dysplasia was noted within their IPNB tumours. Conclusions IPNB is frequently associated with concurrent invasive malignancy. Observation alone is insufficient. Radiological assessment of these tumours remains as the fundamental investigation for diagnosis. However, without confirmatory histology perioperatively, the diagnosis cannot be assured therefore the decision for management must be based upon a patient-centered discussion and a careful evaluation of risk.

Research progress of bile biomarkers and their immunoregulatory role in biliary tract cancers.

Biliary tract cancers (BTCs), including cholangiocarcinoma and gallbladder carcinoma, originate from the biliary epithelium and have a poor prognosis. Surgery is the only choice for cure in the early stage of disease. However, most patients are diagnosed in the advanced stage and lose the chance for surgery. Early diagnosis could significantly improve the prognosis of patients. Bile has complex components and is in direct contact with biliary tract tumors. Bile components are closely related to the occurrence and development of biliary tract tumors and may be applied as biomarkers for BTCs. Meanwhile, arising evidence has confirmed the immunoregulatory role of bile components. In this review, we aim to summarize and discuss the relationship between bile components and biliary tract cancers and their ability as biomarkers for BTCs, highlighting the role of bile components in regulating immune response, and their promising application prospects.