Integrating next-generation sequencing to endoscopic retrograde cholangiopancreatography (ERCP)-obtained biliary specimens improves the detection and management of patients with malignant bile duct strictures

Abstract

ObjectiveDespite improvements in imaging, serum CA19-9 and pathological evaluation, differentiating between benign and malignant bile duct strictures remains a diagnostic conundrum. Recent developments in next-generation sequencing (NGS) have opened new opportunities for early detection and management of cancers but, to date, have not been rigorously applied to biliary specimens.DesignWe prospectively evaluated a 28-gene NGS panel (BiliSeq) using endoscopic retrograde cholangiopancreatography-obtained biliary specimens from patients with bile duct strictures. The diagnostic performance of serum CA19-9, pathological evaluation and BiliSeq was assessed on 252 patients (57 trainings and 195 validations) with 346 biliary specimens.ResultsThe sensitivity and specificity of BiliSeq for malignant strictures was 73% and 100%, respectively. In comparison, an elevated serum CA19-9 and pathological evaluation had sensitivities of 76% and 48%, and specificities of 69% and 99%, respectively. The combination of BiliSeq and pathological evaluation increased the sensitivity to 83% and maintained a specificity of 99%. BiliSeq improved the sensitivity of pathological evaluation for malignancy from 35% to 77% for biliary brushings and from 52% to 83% for biliary biopsies. Among patients with primary sclerosing cholangitis (PSC), BiliSeq had an 83% sensitivity as compared with pathological evaluation with an 8% sensitivity. Therapeutically relevant genomic alterations were identified in 20 (8%) patients. Two patients with ERBB2-amplified cholangiocarcinoma received a trastuzumab-based regimen and had measurable clinicoradiographic response.ConclusionsThe combination of BiliSeq and pathological evaluation of biliary specimens increased the detection of malignant strictures, particularly in patients with PSC. Additionally, BiliSeq identified alterations that may stratify patients for specific anticancer therapies.

Recurrent Rearrangements in PRKACA and PRKACB in Intraductal Oncocytic Papillary Neoplasms of the Pancreas and Bile Duct

“…12 Similarly, endoscopic retrograde cholangiopancreatography (ERCP) was used to obtain bile duct brushings specimens from 2 patients with a biliary IOPN. 13 Among the 20 surgically resected pancreatic IOPNs, DNA-based targeted NGS was negative for genomic alterations in KRAS, GNAS, NRAS, HRAS, BRAF, RNF43, CTNNB1, VHL, PIK3CA, PTEN, TP53, and SMAD4. Similarly, 4 IOPNassociated PDACs and 5 corresponding preoperative EUS-FNAs obtained pancreatic cyst fluid specimens that also tested negative.…”

“…for targeted hotspots within the following genes: AKT1, ALK, ATM, BRAF, CDKN2A, CTNNB1, EGFR, ERBB2, ERBB4, FGFR1, FGFR2, FGFR3, GNA11, GNAQ, GNAS, HRAS, IDH1, IDH2, KIT, KRAS, MET, NRAS, PDGFRA, PIK3CA, PTEN, SMAD4, TP53, and VHL, as previously described. 13 Amplicons were barcoded, ligated with specific adapters, and purified. DNA library quantity and quality checks were performed using the 4200 TapeStation (Agilent Technologies, Santa Clara, CA).…”

Experience and future perspectives on the use of the Papanicolaou Society of Cytopathology Terminology System for reporting pancreaticobiliary cytology

“…In addition, as next‐generation sequencing (NGS) evolves, and becomes cheaper, more sensitive and readily available for cytological samples, routine incorporation in the workup of pancreaticobiliary lesions may clarify potentially “atypical” or “suspicious” cases. This is already happening with cysts and BDB samples . The wide use and acceptance of the PB system may also stimulate the integration between radiological, biochemical and pathological analysis, with a multi‐specialized view of pancreatic lesions, not always available in centers worldwide due to lack of clinical/radiological information listed on the pathological request form, particularly important for biliary cytology, for which a history of stones or stents may level the bar higher for a definite diagnosis of malignancy .…”

“…This is already happening with cysts and BDB samples. [32][33][34][35][36] The wide use and acceptance of the PB system may also stimulate the integration between radiological, biochemical and pathological analysis, with a multi-specialized view of pancreatic lesions, not always available in centers worldwide due to lack of clinical/radiological information listed on the pathological request form, particularly important for biliary cytology, for which a history of stones or stents may level the bar higher for a definite diagnosis of malignancy. 6 In this light, a new name for the second edition of the PB System highlighting the international utility of the system and with input from the many stakeholders of the system warrants consideration-hence, The International System for Reporting Pancreaticobiliary Cytology.…”

Endoskopische Diagnostik der unklaren Gallengangsstenose: Aktueller Stand und Ausblick

“…Diese Methoden können die Sensitivität der Histologie oder Zytologie potenziell erhöhen und stellen so eine gute und technisch einfache Ergänzung dar [47]. In einer 2019 publizierten Studie mit 252 Patienten erreichte die Kombination von NGS und Pathologie eine Sensitivität von 83 % bei einer Spezifität von 99 % [48]. Aufgrund der zunehmend breiteren und kostengünstigeren Anwendung von Panel-Sequenzierungen erscheint perspektivisch eine Implementierung in die Routinediagnostik möglich, umfangreiche prospektive Studien sind jedoch noch ausstehend.…”