Percutaneous endobiliary radiofrequency ablation with stent placement in type IV hilar cholangiocarcinoma: A prospective comparison with stent placement alone.

OBJECTIVES: This study aimed to compare the safety and effectiveness of percutaneous endobiliary radiofrequency ablation with stent placement (RFA group) versus stent placement alone (stent group) in patients with type IV hilar cholangiocarcinoma. METHODS: This prospective nonrandomized study was conducted between October 2021 and April 2023. The study included 56 participants (33 men and 23 women, median age 73 years) who underwent percutaneous endobiliary RFA with stent placement (n = 25) or stent placement alone (n = 31) for type IV hilar cholangiocarcinoma. The primary end point was stent patency, while the secondary end points were procedure-related adverse events (AE) and overall survival. RESULTS: The percutaneous endobiliary RFA and/or stent placement were successfully completed in all patients in both groups. The median stent patency rate was higher in the RFA group than the stent group (188 days vs. 155 days, p = 0.048). There were no differences in AEs (grade 1 [5 in RFA group vs. 5 in stent group, p = 0.74] and grade 2 AEs [2 vs. 4, p = 0.68]) and patients' survival (median 222 days vs. 214 days, p = 0.49) between the two groups. CONCLUSIONS: In patients with type IV hilar cholangiocarcinoma, percutaneous endobiliary RFA with stent placement may improve stent patency without increasing the risk of AEs compared to stent placement alone.

The predictive value of PD-L1 expression in response to anti-PD-1/PD-L1 therapy for biliary tract cancer: a systematic review and meta-analysis.

Background: Recently, anti-programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) immunotherapy offers promising results for advanced biliary tract cancer (BTC). However, patients show highly heterogeneous responses to treatment, and predictive biomarkers are lacking. We performed a systematic review and meta-analysis to assess the potential of PD-L1 expression as a biomarker for treatment response and survival in patients with BTC undergoing anti-PD-1/PD-L1 therapy. Methods: We conducted a comprehensive systematic literature search through June 2023, utilizing the PubMed, EMBASE, and Cochrane Library databases. The outcomes of interest included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) according to PD-L1 expression. Subgroup analyses and meta-regression were performed to identify possible sources of heterogeneity. Results: A total of 30 studies was included in the final analysis. Pooled analysis showed no significant differences in ORR (odds ratio [OR], 1.56; 95% confidence intervals [CIs], 0.94-2.56) and DCR (OR, 1.84; 95% CIs, 0.88-3.82) between PD-L1 (+) and PD-L1 (-) patients. In contrast, survival analysis showed improved PFS (hazard ratio [HR], 0.54, 95% CIs, 0.41-0.71) and OS (HR, 0.58; 95% CI, 0.47-0.72) among PD-L1 (+) patients compared to PD-L1 (-) patients. Sensitivity analysis excluding retrospective studies showed no significant differences with the primary results. Furthermore, meta-regression demonstrated that drug target (PD-1 vs. PD-L1), presence of additional intervention (monotherapy vs. combination therapy), and PD-L1 cut-off level (1% vs. ≥5%) significantly affected the predictive value of PD-L1 expression. Conclusion: PD-L1 expression might be a helpful biomarker for predicting PFS and OS in patients with BTC undergoing anti-PD-1/PD-L1 therapy. The predictive value of PD-L1 expression can be significantly influenced by diagnostic or treatment variables. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42023434114.

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.

Analysis of Recent Improvement of Survival Outcomes in Patients with Pancreatic Cancer Who Underwent Upfront Surgery.

Background/Aims: : Recently, patients with pancreatic cancer (PC) who underwent resection have exhibited improved survival outcomes, but comprehensive analysis is limited. We analyzed the trends of contributing factors. Methods: : Data of patients with resected PC were retrospectively collected from the Korean Health Insurance Review and Assessment Service (HIRA) database and separately at our institution. Cox regression analysis was conducted with the data from our institution a survival prediction score was calculated using the ß coefficients. Results: : Comparison between the periods 2013-2015 (n=3,255) and 2016-2018 (n=3,698) revealed a difference in the median overall survival (25.9 months vs not reached, p<0.001) when analyzed with the HIRA database which was similar to our single-center data (2013-2015 [n=119] vs 2016-2018 [n=148], 20.9 months vs 32.2 months, p=0.003). Multivariable analyses revealed six factors significantly associated with better OS, and the scores were as follows: age >70 years, 1; elevated carbohydrate antigen 19-9 at diagnosis, 1; R1 resection, 1; stage N1 and N2, 1 and 3, respectively; no adjuvant treatment, 2; FOLFIRINOX or gemcitabine plus nab-paclitaxel after recurrence, 4; and other chemotherapy or supportive care only after recurrence, 5. The rate of R0 resection (69.7% vs 80.4%), use of adjuvant treatment (63.0% vs 74.3%), and utilization of FOLFIRINOX or gemcitabine plus nab-paclitaxel (25.2% vs 47.3%) as palliative chemotherapeutic regimen, all increased between the two time periods, resulting in decreased total survival prediction score (mean: 7.32 vs 6.18, p=0.004). Conclusions: : Strict selection of surgical candidates, more use of adjuvant treatment, and adoption of the latest combination regimens for palliative chemotherapy after recurrence were identified as factors of recent improvement.

Real-world dose reduction of standard and modified FOLFIRINOX in metastatic pancreatic cancer: a systematic review, evidence-mapping, and meta-analysis.

Background: FOLFIRINOX, used in metastatic pancreatic cancer (MPC), is highly efficacious but also toxic. Various dose modifications for FOLFIRINOX have been introduced to reduce toxicity. However, these studies lack a unified pattern for 'planned' dose modification, and the 'actually administered' dose varied more. Objective: To map a 10-year trend for 'planned' and 'actual' doses of FOLFIRINOX and investigate the clinical outcomes according to dose modification. Data sources and methods: A comprehensive systematic literature search was conducted from January 2011 to September 2021. All studies for FOLFIRINOX as first-line treatment in MPC were considered. Selected studies were firstly classified according to prospective versus retrospective research, secondly standard versus modified FOLFIRINOX, and thirdly 'planned' versus 'actual' dose. For evidence-mapping for the trend of dose modification, we developed a web-based interactive bubble-plot program (www.RDI-map.com). Objective response rate (ORR) and hematologic toxicity were set as endpoints for the comparison of clinical outcomes according to dose modification. Results: A total of 37 studies were identified for evidence-mapping (11 prospective and 26 retrospective studies). There were 12 different types of 'planned' dose modification in FOLFIRINOX ranging 75-100% oxaliplatin, 75-100% irinotecan, 0-100% 5-fluorouracil (5-FU) bolus, and 75-133% 5-FU continuous injection. The 'actual' dose further decreased to 54-96%, 61-88%, 0-92%, and 63-98%, respectively. For the standard versus modified FOLFIRINOX, the ORR was 28.2% (95% CI: 22.5-33.9%) and 33.8% (95% CI: 30.3-37.3%), respectively (p = 0.100), and the incidence of febrile neutropenia was 11.6% (95% CI: 0-16.0%) and 5.5% (95% CI: 0-8.9%), respectively (p = 0.030). Conclusions: RDI-map.com enables multifactorial evidence-mapping for practical FOLFIRINOX dose reduction. The pattern of dose modification was not consistent across studies, and there was a significant gap between the 'planned' and 'actual' doses. Modified FOLFIRINOX showed similar efficacy to the standard regimen with reduced incidence of febrile neutropenia.

Comparison between three types of needles for endoscopic ultrasound-guided tissue acquisition of pancreatic solid masses: a multicenter observational study.

It is debatable which needle has clear superiority of diagnostic performance in endoscopic ultrasound (EUS)-guided fine needle biopsy (FNB) of solid pancreatic masses. This study aimed to compare the performance of three needles and determine the variables that affect diagnostic accuracy. From March 2014 to May 2020, 746 patients with solid pancreatic masses who underwent EUS-FNB using three types of needles (Franseen needle, Menghini-tip needle, and Reverse-bevel needle) were retrospectively reviewed. Multivariate analysis using a logistic regression model was used to identify factors related to diagnostic accuracy. There were significant differences between the groups regarding the procurement rate of the histologic and optimal quality cores (Franseen vs. Menghini-tip vs. Reverse-bevel: 98.0% [192/196] vs. 85.8% [97/113] vs. 91.9% [331/360], P < 0.001 and 95.4% [187/196] vs. 65.5% [74/113] vs. 88.3% [318/360], P < 0.001, respectively). The sensitivity and accuracy using histologic samples were 95.03% and 95.92% for Franseen, 82.67% and 88.50% for Menghini-tip, and 82.61% and 85.56% for Reverse-bevel needles, respectively. In direct comparison between the needles using histologic samples, the Franseen needle showed significantly superior accuracy than the Menghini-tip (P = 0.018) and Reverse-bevel needles (P < 0.001). Multivariate analysis indicated that tumor size ≥ 2 cm (odds ratio [OR] 5.36, 95% confidence interval [CI] 3.40-8.47, P < 0.001) and fanning technique (OR 1.70, 95% CI 1.00-2.86, P = 0.047) were significantly associated with an accurate diagnosis. EUS-FNB using the Franseen needle enables the acquisition of a larger and more adequate histologic core tissue and achieves an accurate histological diagnosis when using the fanning technique.

Efficacy improvement in searching MEDLINE database using a novel PubMed visual analytic system: EEEvis.

PubMed is the most extensively used database and search engine in the biomedical and healthcare fields. However, users could experience several difficulties in acquiring their target papers facing massive numbers of search results, especially in their unfamiliar fields. Therefore, we developed a novel user interface for PubMed and conducted three steps of study: step A, a preliminary user survey with 76 medical experts regarding the current usability for the biomedical literature search task at PubMed; step B is implementing EEEvis, a novel interactive visual analytic system for the search task; step C, a randomized user study comparing PubMed and EEEvis. First, we conducted a Google survey of 76 medical experts regarding the unmet needs of PubMed and the user requirements for a novel search interface. According to the data of preliminary Google survey, we implemented a novel interactive visual analytic system for biomedical literature search. This EEEvis provides enhanced literature data analysis functions including (1) an overview of the bibliographic features including publication date, citation count, and impact factors, (2) an overview of the co-authorship network, and (3) interactive sorting, filtering, and highlighting. In the randomized user study of 24 medical experts, the search speed of EEEvis was not inferior to PubMed in the time to reach the first article (median difference 3 sec, 95% CI -2.1 to 8.5, P = 0.535) nor in the search completion time (median difference 8 sec, 95% CI -4.7 to 19.1, P = 0.771). However, 22 participants (91.7%) responded that they are willing to use EEEvis as their first choice for a biomedical literature search task, and 21 participants (87.5%) answered the bibliographic sorting and filtering functionalities of EEEvis as a major advantage. EEEvis could be a supplementary interface for PubMed that can enhance the user experience in the search for biomedical literature.

Impact of histopathological type on the prognosis of ampullary carcinoma: A systematic review and meta-analysis.

Histologically, ampullary carcinomas (ACs) can be classified into intestinal (INT-AC) and pancreatobiliary (PB-AC) subtypes. However, the prognostic implications of these subtypes remain unclear. This study aimed to evaluate the impact of the histopathologic phenotype of ACs on survival following pancreaticoduodenectomy. We searched PubMed, Embase, and Medline for studies published in English from 1994 to 2021. A meta-analysis was performed using Review Manager 5.3. The primary endpoint was overall survival (OS). We identified 3,890 articles; of these, 37 articles involving 3,455 participants (1,659 INT-ACs and 1,796 PB-ACs) were included. Patients in the PB-ACs group had significantly shorter OS than those in the INT-ACs group (hazard ratio [HR]: 1.79, 95% confidence interval [95% CI]: 1.51-2.13, p < 0.001, I2 = 61%). A similar tendency was observed in the immunohistochemistry staining group (HR: 1.76, 95% CI: 1.33-2.33, p < 0.001, I2 = 67%), which included 24 studies and 1,638 patients, and the non-immunohistochemistry group (HR: 1.84, 95% CI: 1.53-2.22, p = 0.04, I2 = 46%), which included 13 studies and 1,817 patients. Subgroup analysis revealed that patients with PB-AC had higher frequencies of advanced (III, IV) and pT3-4 stage AC, lymph node metastasis, poorly differentiated tumor, positive surgical margins, lymphovascular invasion, and perineural invasion, than those with INT-AC. Patients with PB-AC had a significantly shorter OS than those with INT-AC due to a higher aggressiveness. Because the histopathologic subtype is a major prognostic factor in patients with resected AC, routine histopathologic classification should be considered even in clinical settings without immunohistochemistry.

Continued adjuvant FOLFIRINOX for BRPC or LAPC after neoadjuvant FOLFIRINOX.

PURPOSE: We aimed to assess the role of adjuvant FOLFIRINOX, in comparison with other adjuvant therapy, in patients who received neoadjuvant FOLFIRINOX and surgery for borderline resectable or locally advanced pancreatic cancer (BRPC or LAPC). METHODS: Our target population was patients with BRPC or LAPC, who received adjuvant therapy following neoadjuvant FOLFIRINOX and surgery between June 2013 and October 2020. Multivariable Cox proportional-hazard model was used to identify factors associated with overall survival (OS) and recurrence free survival (RFS). RESULTS: Among 244 patients with BRPC or LAPC who received neoadjuvant FOLFIRINOX, 79 patients underwent subsequent surgery. Among them, 58 who received adjuvant therapy [median age, 63 years; 33 females (56.9%)] were included. Thirty patients received adjuvant modified FOLFIRINOX (mFOLFIRINOX), while 28 received adjuvant therapy other than FOLFIRINOX. In multivariable analysis, mFOLFIRINOX and post-treatment carbohydrate antigen 19-9 (CA 19-9) were significantly associated with OS and RFS. According to mFOLFIRINOX vs. other adjuvant therapy, median OS was not reached at 37.5 months of follow-up vs. 29.7 months (P = .012); and median RFS was 30.5 vs. 11.0 months (P = .028). According to post-treatment CA 19-9 (< 37 vs. ≥ 37 U/mL), median OS was 46.0 vs. 25.5 months (P = .022); and median RFS was 25.9 vs. 7.6 months (P = .012). CONCLUSION: Continued adjuvant mFOLFIRINOX and post-treatment CA 19-9 level were associated with survival in patients with BRPC or LAPC who received neoadjuvant FOLFIRINOX and surgery. Continued adjuvant mFOLFIRINOX after neoadjuvant FOLFIRINOX could be considered for patients with good performance.

Increased incidence of indeterminate pancreatic cysts and changes of management pattern: Evidence from nationwide data.

BACKGROUND: Pancreatic cysts are common. However, most studies are based on data collected from individual centers. The present study aimed to evaluate the changes of management patterns for pancreatic cystic lesions (PCLs) by analyzing large epidemiologic data. METHODS: Between January 2007 and December 2018, information regarding pancreatic cystic lesions was acquired from the nationwide Health Insurance Review and Assessment Service database in Korea. RESULTS: The final number of patients with pancreatic cysts was 165 277 among the total claims for reimbursement of 855 983 associated with PCLs over 12 years. The total number of claims were increased from 19 453 in 2007 to 155 842 in 2018 and the prevalence increased from 0.04% to 0.23%. For 12 years, 2874 (1.7%) had pancreatic cancer and 8212 (5.0%) underwent surgery, and 36 had surgery for twice (total 8248 pancreatectomy). After ruling out claims from the first 3 years of washout period, the incidence increased from 9891 to 24 651 and the crude incidence rate of PCLs expanded from 19.96 per 100 000 to 47.77 per 100 000. Compared to specific neoplasm codes (D136 or D377), the use of pancreatic cyst code (K862) has been remarkably increased and the most common since 2010. The annual number of pancreatectomies increased from 518 to 861 between 2007 and 2012, and decreased to 596 until 2018. The percentage of pancreatic cancer in patients who received pancreatectomy increased from 5.6% in 2007 to 11.7% in 2018. CONCLUSIONS: The incidence of PCLs is rapidly increasing. Among PCLs, indeterminate cyst is increasing outstandingly. A trend of decreasing in the number of resections and increasing cancer rates among resected cysts may be attributed to the updated international guidelines.

NGS-based targeted gene mutational profiles in Korean patients with pancreatic cancer.

According to molecular profiling studies, a considerable number of patients with pancreatic cancer harbor potentially actionable mutations. However, there are limited relevant data from the Korean population. We assessed the molecular profiles of patients with pancreatic cancer in Korea. This study collected molecular profiling data from patients with pancreatic cancer who visited Seoul National University Bundang Hospital between March 2018 and August 2020. Formalin-fixed, paraffin-embedded tumor specimens were sequenced using a targeted next-generation sequencing (NGS) platform. Cancer-associated mutations were analyzed, and potentially actionable mutations were identified. Potentially actionable mutations were classified into "highly actionable" and "modifies options" based on the Know Your Tumor registry study. In total, 87 patients with NGS tumor panel data were identified. Sixty-one patients (70.1%) had metastatic disease at the time of tissue acquisition. Tissues were obtained from the primary tumors and metastatic sites in 41 (47.1%) and 46 (52.9%) patients, respectively. At least one pathogenic mutation was reported in 86 patients (98.9%). The frequencies of four common mutations in our cohort were similar to those in The Cancer Genome Atlas data. Potentially actionable mutations were identified in 27 patients (31.0%). Of these, mutations categorized as highly actionable and modifies options were identified in 12 (13.8%) and 18 patients (20.7%), respectively. The most frequent highly actionable mutations were located in DNA damage response genes, such as BRCA1, BRCA2, or ATM (n = 6, 6.9%). Two patients with germline BRCA1 mutations received maintenance poly(adenosine diphosphate-ribose) polymerase inhibitor therapy. One patient has been receiving maintenance treatment for 18 months while remaining in radiologically complete remission. Mutational profiles using targeted NGS in Korean patients with pancreatic cancer were similar to those in Western patients. The present study supports the clinical potential and possible expanded clinical use of genetic profiling.

Syringaresinol Alleviates Oxaliplatin-Induced Neuropathic Pain Symptoms by Inhibiting the Inflammatory Responses of Spinal Microglia.

Oxaliplatin-induced peripheral neuropathy (OIPN) is a serious side effect that impairs the quality of life of patients treated with the chemotherapeutic agent, oxaliplatin. The underlying pathophysiology of OIPN remains unclear, and there are no effective therapeutics. This study aimed to investigate the causal relationship between spinal microglial activation and OIPN and explore the analgesic effects of syringaresinol, a phytochemical from the bark of Cinnamomum cassia, on OIPN symptoms. The causality between microglial activation and OIPN was investigated by assessing cold and mechanical allodynia in mice after intrathecal injection of the serum supernatant from a BV-2 microglial cell line treated with oxaliplatin. The microglial inflammatory response was measured based on inducible nitric oxide synthase (iNOS), phosphorylated extracellular signal-regulated kinase (p-ERK), and phosphorylated nuclear factor-kappa B (p-NF-κB) expression in the spinal dorsal horn. The effects of syringaresinol were tested using behavioral and immunohistochemical assays. We found that oxaliplatin treatment activated the microglia to increase inflammatory responses, leading to the induction of pain. Syringaresinol treatment significantly ameliorated oxaliplatin-induced pain and suppressed microglial expression of inflammatory signaling molecules. Thus, we concluded that the analgesic effects of syringaresinol on OIPN were achieved via the modulation of spinal microglial inflammatory responses.

Association between progression-free survival and metal stent patency in patients with advanced pancreatic cancer.

Background: Chemotherapy reportedly affects the patency of self-expandable metal stents (SEMSs) in patients with cancer. However, knowledge regarding the association between SEMS patency and progression-free survival (PFS) remains limited. This study aimed to assess PFS and SEMS patency in patients with advanced pancreatic cancer. Methods: Between January 2012 and June 2021, 74 patients with locally advanced or metastatic pancreatic cancer (MPC) were enrolled in the study. Patients received gemcitabine plus nab-paclitaxel (GnP) or fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFIRINOX) as initial chemotherapy and SEMS within 1 month before or after the initial chemotherapy. Longer PFS was defined as PFS ≥7 months. Results: This study enrolled 38 male patients (51.4%); the mean age was 66.2 [95% confidence interval (CI), 63.7-68.6] years. Of the patients, 46 (62.2%) had MPC and 58 (78.4%) received FOLFIRINOX as the initial chemotherapy. Of the patients, 61 (82.4%) underwent endoscopic SEMS insertion. The median stent patency and PFS were 6.9 [interquartile range (IQR), 4.5-12.9] and 6.4 (IQR, 4.2-12.5) months, respectively; the median overall survival (OS) was 10.5 (IQR, 6.7-16.5) months. Of the clinical parameters assessed using multivariate analysis, shorter PFS [PFS <7 months; hazard ratio (HR), 2.117; 95% CI, 1.020-4.393; P=0.044] and metastatic cancer (HR, 2.414; 95% CI, 1.159-5.018; P=0.019) were found to be associated with shorter SEMS patency. The median SEMS patency in patients with longer PFS and those with shorter PFS was 14.3 and 7.0 months (P=0.012), respectively, and that in patients with locally advanced cancer and those with metastatic cancer was 16.7 and 7.0 months (P=0.006), respectively. The coefficient of determination between stent patency and PFS was 0.624. Conclusions: SEMS patency may be associated with PFS in patients with advanced pancreatic cancer who receive GnP or FOLFIRINOX.

Multi-Phase, Contrast-Enhanced Computed Tomography-Based Radiomic Prognostic Marker of Non-Metastatic Pancreatic Ductal Adenocarcinoma.

Background/Aim: This study investigated the predictive ability of intra-tumor enhancement on computed tomography (CT) for the outcomes of patients with pancreatic ductal adenocarcinoma (PDA). Methods: Multi-phase, contrast-enhanced CT (including unenhanced, pancreatic parenchymal phase (PPP) and portal venous phase (PVP)) images of patients diagnosed with non-metastatic PDA were analyzed to investigate prognostic factors. Results: Two hundred ninety-eight patients with PDA (159 with resectable pancreatic cancer (RPC) and 139 with borderline resectable pancreatic cancer (BRPC)/locally advanced pancreatic cancer (LAPC)) were included. The attenuation values of PDA during the PPP (94.5 vs. 60.7 HU; p <0.001) and PVP (101.5 vs. 75.5 HU; p <0.001) were higher in patients with RPC than in those with BRPC/LAPC. Well-enhanced PDA during the PPP was associated with longer overall survival in the RPC group (27.9 vs. 15.4 months; p <0.001) and the BRPC/LAPC group (22.7 vs. 13.6 months; p = 0.024). Patients with BRPC/LAPC who underwent neoadjuvant treatment and had well-enhanced PDA during the PPP were more likely to undergo resection. Although tumor size was also an independent prognostic factor, it was not correlated with intra-tumoral enhancement during the PPP. Conclusions: Intra-tumoral contrast enhancement on CT is an independent prognostic factor in patients with non-metastatic PDA.

Downregulation of ASF1B inhibits tumor progression and enhances efficacy of cisplatin in pancreatic cancer.

Pancreatic cancer is an aggressive and lethal cancer with the highest mortality rate. Hence, the development of new targeting and innovative treatment strategies is needed. Recent studies reported that the histone chaperone anti-silencing function 1B (ASF1B) can be used as a diagnosis and prognosis cancer biomarker. However, functional studies of ASF1B in pancreatic cancer have not been performed. This study compared expression levels of ASF1B in pancreatic cancer specimens with those of normal tissues using publicly available online databases. We found that ASF1B was commonly overexpressed in pancreatic cancer specimens, which is associated with poor prognosis. ASF1B downregulation in pancreatic cancer cells reduced their colony formation, proliferation, migration, and invasion abilities, and inhibited MMP9 activity. Furthermore, ASF1B expression downregulation increased cell cycle S-phase arrest and DNA damage though activation of the checkpoint kinases Chk1 and Chk2 pathways. Additionally, increased caspase (caspases-3 and -9) activation and PARP cleavage led to enhanced caspase-dependent apoptosis and improved cisplatin sensitivity. Collectively, our results indicate that ASF1B may serve as a potential biomarker of pancreatic cancer and a novel therapeutic target.

Prediction model using clinical factors for radiation exposure during endoscopic retrograde cholangiopancreatography.

BACKGROUND AND AIM: Endoscopic retrograde cholangiopancreatography (ERCP) requires radiation. This study aimed to assess the clinical factors influencing radiation exposure and devise a scoring model for predicting high-dose radiation exposure. METHODS: Endoscopic retrograde cholangiopancreatography cases recorded between 2016 and 2019 in a single tertiary teaching hospital were retrospectively reviewed. A scoring model was created by bootstrap method in a derivation cohort (2016-2018) and was assessed in a validation cohort (2019). RESULTS: Out of 4223 ERCPs, 2983 and 1240 cases were included in the derivation and validation cohorts, respectively. In the derivation cohort, 746 cases (top 25%) comprised the high-dose exposure group, and 2237 cases (bottom 75%) comprised the low-dose exposure group. Nine clinical parameters associated with high-dose exposure were male, pancreatic sphincterotomy, balloon dilatation, biliary or pancreatic drainage, procedures with contrast dye, endoscopist, in-hospital ERCP, and spot image. Stone removal was included by bootstrap analysis. As presented in a nomogram, the weight score of each variable was as follows: male, 1; pancreatic sphincterotomy, 3; balloon dilatation, 7; stone removal, 3; biliary or pancreatic drainage, 5; procedures with contrast dye, 1; endoscopist B, 4; endoscopist C, 5; in-hospital procedure, 3; and spot image, 3. A total score ≥ 15 suggested a high-dose radiation exposure. The sensitivity and specificity of the model for high-dose exposure were 0.562 and 0.813, respectively. In the validation cohort, the model showed reasonable predictability. CONCLUSIONS: Various factors were associated with radiation exposure. The simple scoring system in this study could guide endoscopists in predicting the risk of high-dose radiation exposure.

Transhepatic stent placement for malignant portal vein obstruction: Long term efficacy and factors associated with stent failure.

PURPOSE: To evaluate the long-term efficacy of transhepatic stentplacement in patients with symptomatic malignant portal vein(PV) obstruction and to identify risk factors for stent failure. METHODS: From April 2011 to March 2021, transhepatic stent placement was attempted in 36 patients with symptomatic malignant PV obstruction: naïve (n = 20) or recurrent tumor after surgery (n = 16). Technical success, clinical outcomes, and complications were retrospectively evaluated. Thirteen relevant variables were analyzed to determine risk factors for stent failure. RESULTS: Stent was successfully placed in all but one patient (97.2%, 35/36). Thromboaspiration (n = 9) and jejunal variceal embolization (n = 4) were performed in same session. Symptoms related to portal hypertension were resolved in 30 of the 35 patients (85.7%). There was no procedure-related major complication. During the follow-up period (median 175 days),stentfailures occurred in 8 patients (22.9%): 7 stent thromboses within 90 days and one tumor ingrowth at 715 days after stent placement. The 1-, 6-, 12-month stent patency was 94.1%, 78.2%, and 62.6%, respectively. In multivariate analysis, the presence of PV thrombosisat the time of stent placement was associated with stent failure (HR 7.22; 95% CI 1.26-41.29, p = 0.03). CONCLUSION: Transhepatic stentplacement is a safe and effective treatment for malignant PV obstruction. However, stent failure was common (22.9%) and mostly due to early stent thrombosis. The stent failure was associated with PV thrombosis at the time of stent placement.

Tumor resectability and response on CT following neoadjuvant therapy for pancreatic cancer: inter-observer agreement study.

OBJECTIVES: First, to measure inter-observer agreement regarding tumor resectability and response, and second, to measure diagnostic performance in predicting negative resection margin, on re-staging CTs of patients who received neoadjuvant therapy for pancreatic cancer. METHODS: This retrospective study included patients who received neoadjuvant therapy for borderline resectable pancreatic cancer from 2017 to 2020. Six readers independently evaluated initial staging and re-staging CT images. They categorized the resectability on re-staging CT based on the NCCN guideline, and evaluated tumor response to neoadjuvant therapy according to our proposed criteria on a 5-grade scale. For inter-observer agreement, Gwet's agreement coefficients were used. A crossed random effect model was used to pool the sensitivity and specificity of six readers in predicting negative resection margin. RESULTS: Seventy-seven patients with the median age of 66 (59-70) were included. The pooled agreement for tumor resectability was 0.64 (95% CI, 0.56-0.71) for differentiating the three categories, and 0.84 (0.77-0.91) for differentiating resectable or borderline resectable cancer vs. unresectable cancer. Agreement for tumor response grade was 0.89 (0.85-0.92). The pooled sensitivity and specificity for predicting negative resection margin were 48% (43-52%) and 61% (57-64%), respectively, when only "resectable" on re-staging CT was considered as index test positive. When either "resectable"' or "borderline resectable" was considered as positive, the pooled sensitivity and specificity were 91% (89-94%) and 5% (4-6%), respectively. CONCLUSION: CT can be used reliably with a high inter-observer agreement in selecting candidates for surgery after neoadjuvant therapy of pancreatic cancer. KEY POINTS: • On CT following neoadjuvant therapy of pancreatic cancer, six readers showed high agreement in differentiating resectable or borderline resectable vs. unresectable cancer (Gwet's coefficient, 0.84). • Inter-observer agreement was also high for our proposed tumor response grade (Gwet's coefficient, 0.89). • Specificity was very low (5%) while sensitivity was high (91%) when either resectable or borderline resectable cancer on re-staging CT was considered as predictive of negative resection margin status.

Real-World Outcomes of Gemcitabine, Cisplatin, and Nab-Paclitaxel Chemotherapy Regimen for Advanced Biliary Tract Cancer: A Propensity Score-Matched Analysis.

Background/Aims: Advanced biliary tract cancer (BTC) is associated with poor survival. A recent phase II study of triplet combination chemotherapy, including gemcitabine, cisplatin, and nanoparticle albumin-bound (nab)-paclitaxel, has shown promising results. This study aimed to compare the efficacy of triplet and standard doublet chemotherapy in a real-world setting. Methods: Patients with advanced BTC treated with triplet and doublet chemotherapy regimens were recruited. The propensity-score nearest neighbor matching method with a ratio of one-to-one was used to create a matched cohort for comparison. Progression-free survival (PFS), overall survival (OS), and safety profiles were examined in both groups. Results: A total of 68 patients (n=34 per group) were included in the matched cohort, and their baseline characteristics were well balanced. Survival outcomes in the triplet chemotherapy group were not better than those in the doublet chemotherapy group, with a median PFS of 7.5 months (95% confidence interval [CI], 4.1 to 10.9) versus 7.2 months (95% CI, 5.6 to 8.9) (hazard ratio [HR], 0.93; 95% CI, 0.53 to 1.62; p=0.793) and a median OS of 13.7 months (95% CI, 8.8 to 18.7) versus 12.2 months (95% CI, 8.4 to 16.0) (HR 0.73; 95% CI, 0.38 to 1.41; p=0.354), respectively. In addition, the treatment-related severe adverse events, such as neutropenia, were more common in the triplet chemotherapy group. Conclusions: Gemcitabine, cisplatin, and nab-paclitaxel did not improve the PFS or OS compared to that achieved by standard chemotherapy in patients with advanced BTC. The benefits of triplet chemotherapy in advanced BTC require examination in large randomized controlled trials.