A Short Fully Covered Self-Expandable Metal Stent for Management of Benign Biliary Stricture Not Caused by Living-Donor Liver Transplantation.

Background: This study evaluated the effectiveness of short fully covered self-expanding metal stents (FCSEMS) with an anti-migration design in treating benign biliary strictures (BBS) not related to living donor liver transplantation (LDLT). Methods: A retrospective analysis was conducted on 75 patients who underwent FCSEMS insertion for BBS management. Stents were initially kept for 3 months and exchanged every 3 months until stricture resolution. Adverse events and stricture recurrence after FCSEMS removal were assessed during follow-up. Results: The study outcomes were technical success, stenosis resolution, and treatment failure. Technical success was 100%, with stricture resolution in 99% of patients. The mean onset time of BBS post-surgery was 4.4 years, with an average stent indwelling period of 5.5 months. Stricture recurrence occurred in 20% of patients, mostly approximately 18.8 months after stent removal. Early cholangitis and stent migration were noted in 3% and 4% of patients, respectively. Conclusions: This study concludes that short FCSEMS demonstrate high efficacy in the treatment of non-LDLT-related BBS, with a low incidence of interventions and complications. Although this is a single-center, retrospective study with a limited sample size, the findings provide preliminary evidence supporting the use of short FCSEMS as a primary treatment modality for BBS. To substantiate these findings, further research involving multicenter studies is recommended to provide additional validation and a broader perspective.

Tumour-associated myeloid cells expressing IL-10R2/IL-22R1 as a potential biomarker for diagnosis and recurrence of pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a poor survival rate, largely due to the lack of early diagnosis. Although myeloid cells are crucial in the tumour microenvironment, whether their specific subset can be a biomarker of PDAC progression is unclear. METHODS: We analysed IL-22 receptor expression in PDAC and peripheral blood. Additionally, we analysed gene expression profiles of IL-10R2+/IL-22R1+ myeloid cells and the presence of these cells using single-cell RNA sequencing and murine orthotropic PDAC models, respectively, followed by examining the immunosuppressive function of IL-10R2+/IL-22R1+ myeloid cells. Finally, the correlation between IL-10R2 expression and PDAC progression was evaluated. RESULTS: IL-10R2+/IL-22R1+ myeloid cells were present in PDAC and peripheral blood. Blood IL-10R2+ myeloid cells displayed a gene expression signature associated with tumour-educated circulating monocytes. IL-10R2+/IL-22R1+ myeloid cells from human myeloid cell culture inhibited T cell proliferation. By mouse models for PDAC, we found a positive correlation between pancreatic tumour growth and increased blood IL-10R2+/IL-22R1+ myeloid cells. IL-10R2+/IL-22R1+ myeloid cells from an early phase of the PDAC model suppressed T cell proliferation and cytotoxicity. IL-10R2+ myeloid cells indicated tumour recurrence 130 days sooner than CA19-9 in post-pancreatectomy patients. CONCLUSIONS: IL-10R2+/IL-22R1+ myeloid cells in the peripheral blood might be an early marker of PDAC prognosis.

Endoscopic Ultrasound-guided Fine Needle Aspiration and Biopsy for Cytohistological Diagnosis of Gallbladder Cancer: a multicenter retrospective study.

BACKGROUND AND AIMS: Endoscopic ultrasonography-guided fine-needle aspiration and biopsy (EUS-FNAB) is a standard diagnostic procedure for pancreatic masses but not gallbladder (GB) cancer. We aimed to investigate the efficacy and safety of EUS-FNAB for patients with suspected GB cancer (GBC). METHODS: We analyzed data from patients who underwent EUS-FNAB for suspected GBC in three hospitals between 2010 and 2023. We calculated and compared the diagnostic performance and safety of EUS-FNAB according to characteristic factors. RESULTS: Of 170 patients, 163 had GBC. EUS-FNAB samples were obtained from the GB in 125 patients and sites other than the GB in 45 patients. The overall sensitivity, specificity, and accuracy were 83.4%, 100%, and 84.1%, respectively. The sensitivity and accuracy for patients with GB samples were 80.8% and 81.6%, respectively, whereas those for patients without GB samples were 90.7% and 91.1%, respectively. The sensitivity and accuracy were higher with FNB needles than with FNA needles, and with ≤22-gauge needles than with 25-gauge needles. However, no significant differences were observed between the GB and lymph node (LN) samples. GB lesions <40 mm in size, wall-thickening type, fundal location, absence of extensive liver invasion, and distant metastasis were more frequent in patients without GB samples than in patients with GB samples. Four mild bleeding events were the only reported adverse events. CONCLUSIONS: EUS-FNAB was safe and showed high diagnostic performance for patients with suspected GBC, regardless of the target site. When appropriate GB targeting is difficult, targeting the LNs would be a good strategy with comparable outcomes.

Factors Influencing the Diagnostic Performance of Repeat Endoscopic Ultrasound-Guided Fine-Needle Aspiration/Biopsy after the First Inconclusive Diagnosis of Pancreatic Solid Lesions.

Background/Aims: Endoscopic ultrasound-guided fine-needle aspiration/biopsy (EUS-FNA/B) is essential in diagnosing solid pancreatic lesions (SPLs), but without rapid on-site evaluation (ROSE), a repeat EUS-FNA/B is crucial for clarifying an inconclusive diagnosis. We aimed to evaluate factors associated with improved diagnostic performance of repeat EUS-FNA/B for initially inconclusive SPL diagnoses without ROSE. Methods: Of 5,894 patients subjected to EUS-FNA/B, 237 (4.0%) with an initially inconclusive diagnosis of SPLs were retrospectively enrolled from five tertiary medical centers between January 2016 and June 2021. Diagnostic performance and procedural factors of EUS-FNA/B were analyzed. Results: The diagnostic accuracies of first and repeat EUS-FNA/B were 96.2% and 67.6%, respectively. Of 237 patients with an inconclusive diagnosis from initial EUS-FNA/B, 150 were pathologically diagnosed after repeat EUS-FNA/B. In multivariate analysis of repeat EUS-FNA/B, tumor location (body/tail vs head: odds ratio [OR], 3.74; 95% confidence interval [CI], 1.48 to 9.46), number of needle passes (≥4 vs ≤3: OR, 4.80; 95% CI, 1.44 to 15.99), needle type (FNB vs FNA: OR, 3.26; 95% CI, 1.44 to 7.36), needle size (22 gauge vs 19/20 gauge: OR, 2.35; 95% CI, 1.19 to 4.62), and suction method (suction vs others: OR, 5.19; 95% CI, 1.30 to 20.75) were associated with a significantly improved diagnostic performance. Conclusions: Repeat EUS-FNA/B is essential for patients with an inconclusive EUS-FNA/B without ROSE. To improve the diagnostic performance of repeated EUS-FNA/B, it is recommended that 22-gauge FNB needles, ≥4 needle passes, and suction methods are used.

Prediction of Prognosis in Pancreatic Cancer According to Methionyl-tRNA Synthetase 1 Expression as Determined by Immunohistochemical Staining.

The serum level of CA 19-9 is a prognostic marker for pancreatic ductal adenocarcinoma (PDAC). We evaluated the ability of the expression level of methionyl-tRNA synthetase 1 (MARS1)-which facilitates cancer growth by modulating protein synthesis and the cell cycle-to predict the prognosis of PDAC. Immunohistochemical (IHC) staining was performed on pancreatic specimens obtained from patients with PDAC who were undergoing surgery. High MARS1 expression was defined as equal to, or greater than, that in normal acinar cells. Low MARS1 expression was defined as weaker than in normal acinar cells, and stronger than in the pancreatic duct epithelium. Univariate and multivariate analyses were performed on other factors related to prognosis. Among 137 PDAC patients, no significant differences in baseline characteristics were found between those with high (n = 82) and low (n = 55) MARS1 expression. The median overall survival time of patients with high MARS1 expression was shorter than that of those with low expression (15.2 versus 17.2 months, log-rank test p = 0.044). The median disease-free survival (DFS) was not significantly different between the two groups. However, the DFS was shorter in patients with high than in those with low MARS1 expression (8.9 versus 11.2 months, log-rank test p = 0.067). In a multivariate analysis, lymph node metastasis and high MARS1 expression were associated with a poor prognosis of PDAC. Elevated MARS1 expression detected by IHC staining is associated with a poor prognosis of PDAC, suggesting that MARS1 has potential as a prognostic marker.

Prognostic Impact of Minimal Pelvic Fluid in Locally Advanced Pancreatic Cancer: A Multicenter Retrospective Study.

BACKGROUND/AIMS: Minimal pelvic fluid (MPF) is occasionally encountered on computed tomography (CT) scans during the initial staging of newly diagnosed pancreatic cancer. However, its clinical relevance has scarcely been studied. This study intends to explore the incidence of minimal pelvic fluid and its relevance in terms of survival in locally advanced pancreatic cancer (LAPC) patients. MATERIALS AND METHODS: The medical records of patients with LAPC at 4 tertiary referral institutions were retrospectively reviewed from January 2005 to December 2015. Minimal pelvic fluid was defined as a fluid collection volume in the pelvic cavity of <100 mL as determined by abdominal CT. The association between the presence of MPF and patient survival was evaluated. RESULTS: A total of 59 patients (male:female, 33:26; median age, 68 years; range 46-82 years) with LAPC were enrolled. Of the 59 patients, 22.0% (n = 13) had MPF, and 78.0% (n = 46) had no pelvic fluid (NPF). Baseline clinical characteristics in the 2 groups, including extent of the tumor stage, extent of spread to the lymph nodes stage, and pattern of treatments, were not significantly different. However, median overall survival was significantly less in the MPF group [9.7 months, (95% CI, 5.9-13.5)] than in the NPF group as determined by the log-rank test [16.9 months, (95% CI, 9.3-24.5)] (P = .002), and univariate and multivariate analyses showed that the presence of MPF independently predicted a poor prognosis. CONCLUSION: The presence of MPF was found to be significantly associated with reduced survival and an independent poor prognostic biomarker in LAPC patients.

Improved predictability of pancreatic ductal adenocarcinoma diagnosis using a blood immune cell biomarker panel developed from bulk mRNA sequencing and single-cell RNA-sequencing.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) remains a devastating cancer due to its poor survival rate, early detection, and resectability. This study aimed to determine the peripheral blood mononuclear cell (PBMC) immune biomarkers in patients with PDAC and investigate the PDAC-specific peripheral blood biomarker panel and validate its clinical performance. METHODS: In this prospective, blinded, case-control study, a biomarker panel formula was generated using a development cohort-including healthy controls, patients at high risk of PDAC, and patients with benign pancreatic disease, PDAC, or other gastrointestinal malignancies-and its diagnostic performance was verified using a validation cohort, including patients with ≥ 1 lesion suspected as PDAC on computed tomography (CT). RESULTS: RNA-sequencing of PBMCs from patients with PDAC identified three novel immune cell markers, IL-7R, PLD4, and ID3, as specific markers for PDAC. Regarding the diagnostic performance of the regression formula for the three biomarker panels, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 84.0%, 78.8%, 47.2%, 95.6%, and 79.8%, respectively. Based on the formula scores for the biomarker panel, the false-negative rate (FNR) of the biomarkers was 8% (95% confidence interval [CI] 3.0-13.0), which was significantly lower than that based on CT in the validation cohort (29.2%, 95% CI 20.8-37.6). CONCLUSIONS: The regression formula constructed using three PBMC biomarkers is an inexpensive, rapid, and convenient method that shows clinically useful performance for the diagnosis of PDAC. It aids diagnoses and differential diagnoses of PDAC from pancreatic disease by lowering the FNR compared to CT. Clinical trial registration Clinical Research Information Service, KCT0004614 (08 January 2020).

Efficacy Analysis of Suprapapillary versus Transpapillary Self-Expandable Metal Stents According to the Level of Obstruction in Malignant Extrahepatic Biliary Obstruction.

Background/Aims: The use of a self-expandable metal stent (SEMS) is recommended for unresectable malignant biliary obstruction (MBO). Stent-related adverse events might differ according to the position of the stent through the ampulla of Vater (AOV). We retrospectively evaluated SEMS patency and adverse events according to the position of the SEMS. Methods: In total, 280 patients who underwent endoscopic SEMS placement due to malignant distal biliary obstruction were analyzed retrospectively. Suprapapillary and transpapillary SEMS insertions were performed on 51 patients and 229 patients, respectively. Results: Between the suprapapillary group (SPG) and transpapillary group (TPG), the stent patency period was not significantly different (median [95% confidence interval]: 107 days [82.3 to 131.7] vs 120 days [99.3 to 140.7], p=0.559). There was also no significant difference in the rate of adverse events. In subgroup analysis, the stent patency for an MBO located within 2 cm from the AOV was found to be significantly shorter than that for an MBO located more than 2 cm from the AOV in the SPG (64 days [0 to 160.4] vs 127 days [82.0 to 171.9], p<0.001) and TPG (87 days [52.5 to 121.5] vs 130 [97.0 to 162.9], p<0.001). Patients with an MBO located within 2 cm from the AOV in both groups had a higher percentage of duodenal invasion (SPG: 40.0% vs 4.9%, p=0.002; TPG: 28.6% vs 2.9%, p<0.001) than patients with an MBO located more than 2 cm from the AOV. Conclusions: The SPG and TPG showed similar results in terms of stent patency and rate of adverse events. However, patients with an MBO located within 2 cm from the AOV had a higher percentage of duodenal invasion with shorter stent patency than those with an MBO located more than 2 cm from the AOV, regardless of stent position.

Comparison of Interleukin-6, C-Reactive Protein, Procalcitonin, and the Computed Tomography Severity Index for Early Prediction of Severity of Acute Pancreatitis.

Background/Aims: Acute pancreatitis (AP) is a common gastrointestinal disease associated with hospitalization. With the increase in its incidence, AP has become a greater burden on healthcare resources. Early identification of patients with mild AP can facilitate the appropriate use of resources. We aimed to investigate the ability of inflammatory markers, including interleukin-6 (IL-6), procalcitonin, and C-reactive protein (CRP), as well as various scoring systems to differentiate mild AP from more severe diseases. Methods: We retrospectively investigated patients hospitalized with AP, for whom severity assessment and clinical course confirmation were possible. Inflammatory markers were measured at admission, and CRP levels were measured 24 hours after admission (CRP2). Predictive values were calculated using the area under the receiver operating characteristic curve (AUROC) and logistic regression model analysis. Results: Of 103 patients with AP, 42 (40.8%) were diagnosed with mild AP according to the revised Atlanta classification. Based on the AUROC, IL-6 (0.755, p<0.001), CRP2 (0.787, p<0.001), and computed tomography severity index (CTSI) (0.851, p<0.001) were useful predictors of mild AP. With standard cutoff values, the diagnostic sensitivity, specificity, and accuracy were 83.3%, 62.3%, and 70.9% for IL-6 (<50 pg/mL), and 78.6%, 63.9%, and 69.9% for CRP2 (<50 mg/L), respectively. The AUROC of IL-6 and CRP2 were significantly higher than those of other inflammatory markers and were not significantly different from that of CTSI. Conclusions: IL-6, CRP2, and CTSI are helpful for early differentiation of AP severity. Among inflammatory markers, IL-6 has the advantage of early prediction of mild pancreatitis at the time of admission.

Safety and Efficacy of Allogeneic Natural Killer Cells in Combination with Pembrolizumab in Patients with Chemotherapy-Refractory Biliary Tract Cancer: A Multicenter Open-Label Phase 1/2a Trial.

BACKGROUND AND AIM: This study investigated the administration of combination therapy, allogeneic natural killer (NK) cells and pembrolizumab in the treatment of advanced biliary tract cancer to determine the safety and tolerability (phase 1) and the efficacy and safety (phase 2a). METHODS: Forty patients (phase 1, n = 6; phase 2a, n = 34) were enrolled between December 2019 and June 2021. The patients received highly activated allogeneic NK cells ("SMT-NK") on weeks 1 and 2 and pembrolizumab on week 1. This 3-week schedule (one cycle) was repeated until confirmed disease progression, intolerable adverse events (AEs), patient withdrawal, or finishing the maximum treatment schedule. The tumor response was evaluated after every three cycles. RESULTS: In phase 1, four patients (66.7%) experienced seven AEs, but no severe AE was observed. In phase 2a, 126 AEs occurred in 29 patients (85.3%). Severe AEs (≥grade 3) were reported in 16 patients (47.1%). The overall response rate (ORR) was 17.4% in the full analysis set and 50.0% in the per-protocol set. CONCLUSIONS: SMT-NKs plus pembrolizumab resulted in no severe AEs directly related to the drug combination. The combination therapy also exerted antitumor activity with improved efficacy compared to the recent monotherapy with pembrolizumab in patients with advanced biliary tract cancer.

Safety and Efficacy of a Large-Bore Biliary Metallic Stent for Malignant Biliary Obstruction.

Self-expandable metallic stents (SEMSs) are typically inserted in patients with unresectable malignant biliary obstruction. However, SEMSs are susceptible to occlusion. To overcome this issue, we developed a large-bore, dumbbell-shaped, fully covered SEMS (FCSEMS-L) and compared its efficacy and safety with those of a conventional FCSEMS (FCSEMS-C) in patients with malignant biliary obstruction. METHODS: Patients with unresectable distal malignant biliary obstruction were retrospectively enrolled between January 2011 and February 2021. All patients underwent endoscopic insertion of FCSEMSs. Recurrent biliary obstruction (RBO), patient survival time, complications, and prognosis were analyzed. RESULTS: RBO occurred in 31 patients (35.6%) who received an FCSEMS-L, and in 34 (45.9%) who received an FCSEMS-C. Stent occlusion occurred in 19 patients (21.8%) who received an FCSEMS-L, and in 22 (29.7%) who received an FCSEMS-C. Stent migration occurred in 12 patients (13.8%) with an FCSEMS-L and 12 (16.2%) with an FCSEMS-C. The median time to RBO (TRBO) was 301 days with an FCSEMS-L and 203 days with an FCSEMS-C. The median survival time was 479 days with an FCSEMS-L and 523 days with an FCSEMS-C. The TRBO and patient survival time did not significantly differ between the two groups. CONCLUSIONS: There were no significant differences in efficacy and complication rates between the fully covered large bore SEMSs and conventional fully covered SEMSs.

Efficacy of Chenodeoxycholic Acid and Ursodeoxycholic Acid Treatments for Refractory Functional Dyspepsia.

Refractory functional dyspepsia (RFD) is diagnosed when symptoms persist for at least 6 months despite at least two medical treatments. No consensus treatment guidelines exist. The implicated causes of functional biliary dyspepsia are a narrowed cystic duct, Sphincter of Oddi dysfunction, microlithiasis, and gallbladder dyskinesia. We investigated the treatment effects of litholytic agents. RFD patients were prospectively enrolled in six tertiary medical centers. All subjects took chenodeoxycholic and ursodeoxycholic acids (CNU) twice daily for 12 weeks. We monitored their medication adherence, laboratory results, and complications. The 7-point global symptom scale test scores were determined before and after treatment. Of the 52 patients who were prospectively screened, 37 were included in the final analysis. The mean age was 51.3 years: 14 were males, and 23 were females. Before treatment, the mean number and duration of symptoms were 2.4 and 48.2 months, and a mean of 3.3 FD-related drugs were taken. The mean CNU adherence was 95.3%. The mean global symptom scale score decreased from 5.6 pretreatment to 2.6 posttreatment. The symptom improvement rate was 94.6% (35 out of 37 patients). The only adverse event was mild diarrhea (10.8%) that was resolved after conservative management. Conclusions: CNU improved the symptoms of RFD patients who did not respond to conventional medications. Litholytic agents are good treatment options for patients with RFD and biliary dyspepsia secondary to biliary microlithiasis. Further prospective, large-scale mechanistic studies are warranted.

The role of Jagged1 as a dynamic switch of cancer cell plasticity in PDAC assembloids.

Background: Pancreatic ductal adenocarcinoma (PDAC), which commonly relapses due to chemotherapy resistance, has a poor 5-year survival rate (< 10%). The ability of PDAC to dynamically switch between cancer-initiating cell (CIC) and non-CIC states, which is influenced by both internal and external events, has been suggested as a reason for the low drug efficacy. However, cancer cell plasticity using patient-derived PDAC organoids remains poorly understood. Methods: First, we successfully differentiated CICs, which were the main components of PDAC organoids, toward epithelial ductal carcinomas. We further established PDAC assembloids of organoid-derived differentiated ductal cancer cells with endothelial cells (ECs) and autologous immune cells. To investigate the mechanism for PDAC plasticity, we performed single-cell RNA sequencing analysis after culturing the assembloids for 7 days. Results: In the PDAC assembloids, the ECs and immune cells acted as tumor-supporting cells and induced plasticity in the differentiated ductal carcinomas. We also observed that the transcriptome dynamics during PDAC re-programming were related to the WNT/beta-catenin pathway and apoptotic process. Interestingly, we found that WNT5B in the ECs was highly expressed by trans interaction with a JAG1. Furthermore, JAG1 was highly expressed on PDAC during differentiation, and NOTCH1/NOTCH2 were expressed on the ECs at the same time. The WNT5B expression level correlated positively with those of JAG1, NOTCH1, and NOTCH2, and high JAG1 expression correlated with poor survival. Additionally, we experimentally demonstrated that neutralizing JAG1 inhibited cancer cell plasticity. Conclusions: Our results indicate that JAG1 on PDAC plays a critical role in cancer cell plasticity and maintenance of tumor heterogeneity.

Comparison of the Malignant Predictors in Intrahepatic and Extrahepatic Intraductal Papillary Neoplasm of the Bile Duct.

Background: Intraductal papillary neoplasm of the bile duct (IPNB) is a precancerous lesion of cholangiocarcinoma, for which surgical resection is the most effective treatment. We evaluated the predictors of malignancy in IPNB according to anatomical location and the prognosis without surgery. Methods: A total of 196 IPNB patients who underwent pathologic confirmation by surgical resection or endoscopic retrograde cholangiography or percutaneous transhepatic cholangioscopic biopsy were included. Clinicopathological findings of IPNB with invasive carcinoma or mucosal dysplasia were analyzed according to anatomical location. Results: Of the 116 patients with intrahepatic IPNB (I-IPNB) and 80 patients with extrahepatic IPNB (E-IPNB), 62 (53.4%) and 61 (76.3%) were diagnosed with invasive carcinoma, respectively. Multivariate analysis revealed that mural nodule > 12 mm (p = 0.043) in I-IPNB and enhancement of mural nodule (p = 0.044) in E-IPNB were predictive factors for malignancy. For pathologic discrepancy before and after surgery, IPNB has a 71.2% sensitivity and 82.3% specificity. In the non-surgical IPNB group, composed of nine I-IPNB and seven E-IPNB patients, 43.7% progressed to IPNB with invasive carcinoma within 876 days. Conclusions: E-IPNB has a higher rate of malignancy than I-IPNB. The predictive factor for malignancy is mural nodule > 12 mm in I-IPNB and mural nodule enhancement in E-IPNB.

Validation of IL-7R as an Immunological Biomarker for Human Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer for which no early diagnostic method is available. The immune surveillance hypothesis suggests that the immune system plays crucial roles in tumor development and progression. We validated a PDAC-specific biomarker derived from peripheral blood mononuclear cells (PBMCs) to facilitate early PDAC diagnosis. mRNA levels of interleukin-7R (IL-7R), reportedly a potential immunological marker for PDAC, were measured in PBMCs isolated prospectively from healthy controls (n = 100) and patients with PDAC (n = 135), pancreatic cysts (n = 82), chronic pancreatitis (n = 42), acute pancreatitis (n = 47), and other malignancies (n = 116). The IL-7R level was significantly higher in patients with PDAC than in healthy controls, patients with benign pancreatic disease, and patients with other malignancies. As diagnostic parameters, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for IL-7R were 58.5%, 92%, 90.8%, 62.2%, and 72.8%, respectively. The area under the receiver operating characteristic curve (AUROC) was 0.766. IL-7R levels did not differ between resectable and unresectable PDAC cases. The combined measurement of IL-7R and carbohydrate antigen 19-9 (CA19-9) significantly improved the diagnostic parameters and AUROC compared with the use of IL-7R or CA19-9 alone. IL-7R is significantly upregulated in PBMCs in patients with PDAC, and it may be a novel diagnostic marker for PDAC. The combined use of IL-7R and CA19-9 enhanced the diagnostic performance.

BRCA 1/2 Germline Mutation Predicts the Treatment Response of FOLFIRINOX with Pancreatic Ductal Adenocarcinoma in Korean Patients.

We evaluated the proportion of BRCA 1/2 germline mutations in Korean patients with sporadic pancreatic ductal adenocarcinoma (PDAC) and its effect on the chemotherapeutic response of FOLFIRINOX. This retrospective study included patients who were treated at two tertiary hospitals between 2012 and 2020, were pathologically confirmed to have PDAC, and had undergone targeted next-generation sequencing-based germline genetic testing. Sixty-six patients were included in the study (24 men; median age 57.5 years). In the germline test, BRCA 1/2 pathogenic mutations were found in nine patients (9/66, 13%, BRCA 1, n = 3; BRCA 2, n = 5; and BRCA 1/2, n = 1). There was no significant difference in the baseline characteristics according to BRCA mutation positivity. Among patients who underwent FOLFIRINOX chemotherapy, patients with a BRCA 1/2 mutation showed a higher overall response rate than those without a BRCA 1/2 mutation (71.4% vs. 13.9%, p = 0.004). Patients with a germline BRCA 1/2 mutation showed longer progression-free survival than those without a BRCA 1/2 mutation, without a significant time difference (18 months vs. 10 months, p = 0.297). Patients with a BRCA 1/2 mutation in the germline blood test had a higher response rate to FOLFIRINOX chemotherapy in PDAC. The high proportion of BRCA 1/2 germline mutations and response rate supports the need for germline testing in order to predict better treatment response.

[Recent Updates on Endoscopic Retrograde Cholangiography-guided Intraductal Radiofrequency Ablation for Malignant Biliary Stricture].

Malignant biliary strictures are caused by pancreatobiliary cancer and other metastatic malignancies. Most of them are unresectable at diagnosis with a dismal prognosis. Various new ablation methods have been introduced. Of them, ERCP-guided intraductal radiofrequency ablation (ID-RFA) appears to be the most promising minimally invasive endoscopic treatment by delivering a high-frequency alternating current to the target tissue, leading to coagulative necrosis. Thus far, many studies have provided evidence that ERCP-guided ID-RFA is a safe, feasible, and effective treatment modality for stent patency and overall survival. Compared to other ablation treatments, ERCP-guided ID-RFA has several advantages, including ease of delivery, controlled application of thermal energy, low cost, and fewer systemic side effects with an acceptable safety profile. Therefore, ERCP-guided ID-RFA can be considered an adjunctive treatment for the palliation of unresectable malignant biliary strictures. On the other hand, the decision of local ablation treatment should be individualized by multidisciplinary team support due to the lack of comparative studies.

Characterization of Circulating IL-7R Positive Cell Populations for Early Detection of Pancreatic Ductal Adenocarcinoma.

(1) Background: Pancreatic cancer is a high devastating disease with the lowest survival rate among all common cancers due to difficulties in early diagnosis. The purpose of this study was to identify and characterize the distinct subset of blood cell population elevated in peripheral blood mononuclear cells (PBMC) of pancreatic cancer to evaluate the potential markers for diagnosis of pancreatic cancer; (2) Methods: We analyzed differential gene expression in PBMC from normal individuals and pancreatic cancer patients utilizing transcriptome analysis. Flow cytometry analysis was applied to identify the discrete subset of interleukin-7 receptor (IL-7R) expressing cells in these cells. The expression of IL-7R during tumorigenesis was determined in syngeneic mouse model of pancreatic cancer in vivo; (3) Results: PBMC from pancreatic cancer patients expressed elevated IL-7R mRNA compared to healthy control individuals. IL-7R expressing cells rapidly appeared from the early stages of the onset of tumor formation in syngeneic pancreatic cancer mouse model in vivo. The discrete subset of IL-7R positive cells mainly consist of naive T, central memory T, and effector memory T cells; (4) Conclusions: Taken together, our present findings suggest that pancreatic cancer patients expressed higher level of IL-7R expression in PBMC that rapidly emerged from the onset of early pancreatic tumor formation in vivo than normal individuals. Thus, it can be used as a novel biological marker for early events of pancreatic cancer development.

Comparison of the Clinical Features and Outcomes of Gallbladder Neuroendocrine Carcinoma with Those of Adenocarcinoma: A Propensity Score-Matched Analysis.

Neuroendocrine neoplasms (NENs) of the gallbladder (GB) are extremely rare. We aimed to compare the clinical features, disease progression, management, and prognosis of patients with GB-NENs with those of patients with GB-adenocarcinomas (ADCs). A total of 21 patients with GB-NENs and 206 patients with GB-ADCs, treated at three tertiary medical centers between January 2010 and December 2020, were enrolled. Of the 21 patients with GB-NENs, 20 were diagnosed with poorly differentiated small-cell neuroendocrine carcinomas (NECs), and 1 patient had large-cell NEC. All patients presented with advanced stages of cancer with extensive local extension and/or distant metastasis and non-specific symptoms. Tumor-node-metastasis stage IIIB and IV (A/B) tumors were found in 6 and 15 (1/14) patients, respectively. Nine patients with GB-NEC who underwent surgical resection had a significantly better progression-free survival (PFS) than those who did not undergo surgery. After a propensity score matching with a 1:1 ratio using the American Joint Committee on Cancer stage, age, sex, and operation status, 19 pairs of patients were included. Compared with stage-matched patients with GB-ADC, patients with GB-NEC had similar overall survival and PFS. However, as GB-NEC is rarely diagnosed early, further studies investigating methods for the early diagnosis and improvement in the survival of patients with GB-NEC are needed.

Diagnostic performance of endoscopic ultrasound-artificial intelligence using deep learning analysis of gallbladder polypoid lesions.

BACKGROUND AND AIM: Endoscopic ultrasound (EUS) is the most accurate diagnostic modality for polypoid lesions of the gallbladder (GB), but is limited by subjective interpretation. Deep learning-based artificial intelligence (AI) algorithms are under development. We evaluated the diagnostic performance of AI in differentiating polypoid lesions using EUS images. METHODS: The diagnostic performance of the EUS-AI system with ResNet50 architecture was evaluated via three processes: training, internal validation, and testing using an AI development cohort of 1039 EUS images (836 GB polyps and 203 gallstones). The diagnostic performance was verified using an external validation cohort of 83 patients and compared with the performance of EUS endoscopists. RESULTS: In the AI development cohort, we developed an EUS-AI algorithm and evaluated the diagnostic performance of the EUS-AI including sensitivity, specificity, positive predictive value, negative predictive value, and accuracy. For the differential diagnosis of neoplastic and non-neoplastic GB polyps, these values for EUS-AI were 57.9%, 96.5%, 77.8%, 91.6%, and 89.8%, respectively. In the external validation cohort, we compared diagnostic performances between EUS-AI and endoscopists. For the differential diagnosis of neoplastic and non-neoplastic GB polyps, the sensitivity and specificity were 33.3% and 96.1% for EUS-AI; they were 74.2% and 44.9%, respectively, for the endoscopists. Besides, the accuracy of the EUS-AI was between the accuracies of mid-level (66.7%) and expert EUS endoscopists (77.5%). CONCLUSIONS: This newly developed EUS-AI system showed favorable performance for the diagnosis of neoplastic GB polyps, with a performance comparable to that of EUS endoscopists.