EUS-guided FNA and biopsy for cytohistologic diagnosis of gallbladder cancer: a multicenter retrospective study.

BACKGROUND AND AIMS: EUS-guided FNA and biopsy (EUS-FNAB) is a standard diagnostic procedure for pancreatic masses but not gallbladder (GB) cancer (GBC). The aim of this study was to investigate the efficacy and safety of EUS-FNAB for patients with suspected GBC. METHODS: Data were analyzed from patients who underwent EUS-FNAB for suspected GBC in 3 hospitals between 2010 and 2023. The diagnostic performance and safety of EUS-FNAB according to characteristic factors were calculated and compared. 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%; for patients without GB samples, these values were 90.7% and 91.1%. The sensitivity and accuracy were higher with fine-needle biopsy 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 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 lymph nodes 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.

Diagnostic performance of endoscopic ultrasound elastography for differential diagnosis of solid pancreatic lesions: A propensity score-matched analysis.

BACKGROUND: Endoscopic ultrasound-elastography (EUS-EG) is a non-invasive complementary diagnostic method for differential diagnosis of solid pancreatic lesions (SPL). However, the optimal strain ratio (SR) value and diagnostic performance of EUS-EG have not yet been determined in pancreatic neuroendocrine neoplasm (PNEN), mass-forming pancreatitis (MFP), and pancreatic ductal adenocarcinoma (PDAC). We aimed to determine the optimal SR value in EUS-EG for differential diagnosis of SPLs. METHODS: Patients who underwent EUS-EG for SPL evaluation between July 2016 and June 2019 were retrospectively investigated. Patients were divided into three groups based on the final diagnosis (PNEN, MFP, or PDAC). Patient demographics, characteristics of SPL, and EUS-EG were compared. RESULTS: The mean (± standard deviation) SR value for each group were 11.85 ± 7.56 (PNEN, n = 10), 11.45 ± 5.97 (MFP, n = 37), and 22.50 ± 13.19 (PDAC, n = 87). Multinomial logistic regression analysis revealed that an increase of SR value was significantly associated with PDAC (PNEN versus PDAC, p = 0.0216; MFP versus PDAC, p = 0.0006). The optimal cut-off value for differential diagnosis was confirmed as 17.14 after propensity score matching. CONCLUSIONS: We provided the optimal cut-off SR values for differential diagnosis between MFP and PDAC. EUS-EG can be used as a supplementary diagnostic method in the diagnosis of SPLs. (Clinical trial registration number: https://cris.nih.go.kr/cris: KCT0002082).

Machine-Learning Model for the Prediction of Hypoxaemia during Endoscopic Retrograde Cholangiopancreatography under Monitored Anaesthesia Care.

PURPOSE: Hypoxaemia is a significant adverse event during endoscopic retrograde cholangiopancreatography (ERCP) under monitored anaesthesia care (MAC); however, no model has been developed to predict hypoxaemia. We aimed to develop and compare logistic regression (LR) and machine learning (ML) models to predict hypoxaemia during ERCP under MAC. MATERIALS AND METHODS: We collected patient data from our institutional ERCP database. The study population was randomly divided into training and test sets (7:3). Models were fit to training data and evaluated on unseen test data. The training set was further split into k-fold (k=5) for tuning hyperparameters, such as feature selection and early stopping. Models were trained over k loops; the i-th fold was set aside as a validation set in the i-th loop. Model performance was measured using area under the curve (AUC). RESULTS: We identified 6114 cases of ERCP under MAC, with a total hypoxaemia rate of 5.9%. The LR model was established by combining eight variables and had a test AUC of 0.693. The ML and LR models were evaluated on 30 independent data splits. The average test AUC for LR was 0.7230, which improved to 0.7336 by adding eight more variables with an l1 regularisation-based selection technique and ensembling the LRs and gradient boosting algorithm (GBM). The high-risk group was discriminated using the GBM ensemble model, with a sensitivity and specificity of 63.6% and 72.2%, respectively. CONCLUSION: We established GBM ensemble model and LR model for risk prediction, which demonstrated good potential for preventing hypoxaemia during ERCP under MAC.

Covered versus uncovered double bare self-expandable metal stent for palliation of unresectable extrahepatic malignant biliary obstruction: a randomized controlled multicenter trial.

BACKGROUND AND AIMS: In a recent randomized controlled trial, a double bare metal stent (DBS) showed better stent patency than single-layer metal stents. However, clear evidence comparing the efficacy of uncovered (UCDBS) and partially covered (PCDBS) DBSs for distal malignant biliary obstruction (MBO) is lacking. Therefore, we compared the clinical outcomes including stent patency of UCDBSs versus PCDBSs. METHODS: A multicenter, randomized study was performed in patients with distal MBO. The primary endpoint was stent patency. Secondary endpoints were the proportion of patients with patent stents at 6 months, risk factors for stent dysfunction, overall survival, technical and clinical success rates of stent placement, and other adverse events (AEs). RESULTS: Among 258 included patients, 130 were randomly assigned to the PCDBS group and 128 to the UCDBS group. The mean duration of stent patency of the PCDBS (421.2 days; 95% confidence interval [CI], 346.7-495.7) was longer than that of the UCDBS (377.4 days; 95% CI, 299.7-455.0), although total stent dysfunction and stent dysfunction within 6 months were not different between groups. Multivariate analysis indicated that chemotherapy after stent placement was a significant factor for overall survival (hazard ratio, .570; 95% CI, .408-.796) and had a marginal impact on stent patency (hazard ratio, 1.569; 95% CI, .923-2.667). There were no remarkable differences in AEs, including pancreatitis, cholecystitis, and stent migration, between the 2 groups. CONCLUSIONS: The use of PCDBSs compared with UCDBSs in patients with distal MBO has unclear benefits regarding stent patency and overall survival, although PCDBSs have a lower rate of tumor ingrowth. (Clinical trial registration number: NCT02937246.).

Evaluation of the 8th Edition AJCC Staging System for the Clinical Staging of Pancreatic Cancer.

The 8th edition of the American Joint Committee on Cancer (AJCC) staging system for pancreatic cancer (PC) has been validated for pathological staging; however, its significance for clinical staging remains uncertain. We validated the prognostic performance and suitability of the current staging system for the clinical staging of PC. We identified 1043 patients from our PC registry who were staged by imaging according to the 8th edition staging system and conducted analysis, including overall survival (OS) comparison. Gradual prognostic stratification according to stage hierarchy yielded significant OS differences between stage groups, except between stage I and II (p = 0.193). A substage comparison revealed no survival differences between IB (T2N0) and IIA (T3N0), which were divided by the T3 criterion only (p = 0.278). A higher N stage had significantly shorter OS than a lower N stage (all pairwise p < 0.05). However, among the 150 patients who received upfront surgery, the pathological stage was more advanced than the clinical stage in 86 (57.3%), mostly due to a false-negative cN0 (70.9%). Our results suggest that the new definition of T3 and the number-based N criteria in the 8th edition AJCC staging system may be not adequate for clinical staging. Establishing separate criteria more suitable for clinical staging should be considered.

Efficacy and safety of temperature-controlled intraductal radiofrequency ablation in advanced malignant hilar biliary obstruction: A pilot multicenter randomized comparative trial.

PURPOSE: We aimed to evaluate the efficacy and safety of temperature-controlled intraductal radiofrequency ablation (ID-RFA) for advanced malignant hilar biliary obstruction (MHBO). METHODS: Patients were randomly assigned to RFA group (ID-RFA and bilateral plastic stent [PS]) or non-RFA group (bilateral PS) at a 1:1 ratio. Exchange to self-expanding metal stent (SEMS) was performed after 3 months or when premature PS occlusion occurred. Total event-free stent patency, overall survival (OS), and adverse events (AEs) were analyzed. RESULTS: A total of 30 patients from three hospitals were enrolled. Stent patency and OS did not differ between the two groups (178 days vs 122 days, P = .154; 230 days vs 144 days, P = .643; respectively). In patients with each stricture length ≥11 mm on both sides, stent patency was longer in the RFA group than in the non-RFA group (175 days vs 121 days, P = .028). More patients received elective exchange to SEMS without PS occlusion in the RFA group than in the non-RFA group (69.2% vs 23.1%, P = .018). AE rates did not differ between the two groups. CONCLUSIONS: Temperature-controlled ID-RFA for advanced MHBO was safe and feasible. It could prevent premature PS occlusion within 3 months.

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.

Profiling of conditionally reprogrammed cell lines for in vitro chemotherapy response prediction of pancreatic cancer.

BACKGROUND: The establishment of patient-derived models for pancreatic ductal adenocarcinoma (PDAC) using conventional methods has been fraught with low success rate, mainly because of the small number of tumour cells and dense fibrotic stroma. Here, we sought to establish patient-derived model of PDAC and perform genetic analysis with responses to anticancer drug by using the conditionally reprogrammed cell (CRC) methodology. METHODS: We performed in vitro and in vivo tumourigenicity assays and analysed histological characteristics by immunostaining. We investigated genetic profiles including mutation patterns and copy number variations using targeted deep sequencing and copy-number analyses. We assessed the responses of cultured CRCs to the available clinical anticancer drugs based on patient responsiveness. FINDINGS: We established a total of 28 CRCs from patients. Of the 28 samples, 27 showed KRAS mutations in codon 12/13 or codon 61. We found that somatic mutations were shared in the primary-CRC pairs and shared mutations included key oncogenic mutations such as KRAS (9 pairs), TP53 (8 pairs), and SMAD4 (3 pairs). Overall, CRCs preserved the genetic characteristics of primary tumours with high concordance, with additional confirmation of low-AF NPM1 mutation in CRC (35 shared mutations out of 36 total, concordance rate=97.2%). CRCs of the responder group were more sensitive to anticancer agents than those of the non-responder group (P < 0.001). INTERPRETATION: These results show that a pancreatic cancer cell line model can be efficiently established using the CRC methodology, to better support a personalized therapeutic approach for pancreatic cancer patients. FUNDING: 2014R1A1A1006272, HI19C0642-060019, 2019R1A2C2008050, 2020R1A2C209958611, and 2020M3E5E204028211.

Comparison of contrast-enhanced versus conventional EUS-guided FNA/fine-needle biopsy in diagnosis of solid pancreatic lesions: a randomized controlled trial.

BACKGROUND AND AIMS: Contrast-enhanced harmonic EUS (CEH-EUS) is useful in the differential diagnosis of solid pancreatic lesions (SPLs). However, there is lack of verification about the usefulness of CEH-EUS-guided FNA/fine-needle biopsy (FNB) sampling. This study aimed to investigate the usefulness of CEH-EUS-guided FNA/FNB sampling without on-site cytopathology. METHODS: Patients with SPLs were prospectively enrolled and randomly assigned (1:1) to 2 parallel groups, the interventional group (CEH-EUS) or the control group (conventional EUS). The diagnostic sensitivity and optimal number of needle passes for pathologic diagnosis were investigated and compared between groups. RESULTS: Two hundred forty patients were enrolled from March 2016 to September 2019, with 120 patients assigned to each group. Pancreatic malignancies and neuroendocrine tumors were found in 202 (90.83%) and 9 (3.75%) patients, respectively. There was no statistically significant difference between the groups in terms of age, sex, lesion size (30.96 ± 12.09 mm in the CEH-EUS group vs 33.09 ± 16.39 mm in the conventional EUS group; P = .252), lesion location, adverse event rate, and disease distribution. The diagnostic sensitivity values in the CEH-EUS and conventional EUS groups were 85.8% and 88.3%, respectively (P = .564). All patients in the conventional EUS group and most in the CEH-EUS group received a pathologic diagnosis within 3 needle passes. CONCLUSIONS: Diagnostic sensitivity for SPLs was not different between the CEH-EUS and conventional EUS groups, and no independent factors were found that could improve diagnostic sensitivity. CEH-EUS-guided FNA/FNB sampling does not need to be used routinely and may be selectively considered for small, indeterminate lesions. (Clinical trial registration number: KCT 0001840.).

Efficacy and safety of palliative endobiliary radiofrequency ablation using a novel temperature-controlled catheter for malignant biliary stricture: a single-center prospective randomized phase II TRIAL.

BACKGROUND: Endobiliary radiofrequency ablation (EB-RFA) has emerged as a palliative treatment for malignant biliary strictures (MBSs); however, concerns about complications related to thermal injury remain. In this study, we evaluated the efficacy and safety of EB-RFA with a novel catheter for MBS. METHODS: Patients with inoperable cancer causing MBS were randomly assigned to either the radiofrequency ablation (RFA) group or the non-RFA group. The RFA group underwent EB-RFA at the stricture site with a temperature-controlled catheter (ELRA™; STARmed Co., Goyang, Korea) followed by deployment of a self-expanding metal stent (SEMS). For the non-RFA group, only SEMS placement was performed. The duration of stent patency, overall survival (OS), and 30-day complication rate were evaluated. This trial was registered at ClinicalTrials.gov (number NCT02646514). RESULTS: A total of 48 patients were enrolled (24 in each group). During a median follow-up period of 135.0 days (RFA group) and 119.5 days (non-RFA group), the 90-day stent patency rate, median duration of stent patency, and median OS were not different between the groups (58.3% vs. 45.8% [P = 0.386], 132.0 days vs. 116.0 days [P = 0.440], and 244.0 days vs. 180.0 days [P = 0.281], respectively). In the RFA group, procedure-related complications including thermal injury-related complications, such as bile duct perforation or hemobilia, were not reported. The early complication (< 7 days) rates were not different between the groups (4.2% vs. 12.5%, P = 0.609), and there were no late complications (7-30 days) in both groups. CONCLUSION: EB-RFA with a temperature-controlled catheter followed by SEMS placement for patients with inoperable MBS can be safe and feasible with acceptable biliary patency.

Peripheral natural killer cell activity is associated with poor clinical outcomes in pancreatic ductal adenocarcinoma.

BACKGROUND AND AIM: We aimed to measure the natural killer (NK) cell activity and pro-inflammatory cytokine levels in the peripheral blood of pancreatic cancer patients and investigate the correlation of NK cell activity and cytokines with cancer status and clinical outcomes. METHODS: We prospectively enrolled patients who were pathologically diagnosed with pancreatic ductal adenocarcinoma (PDAC) between 2016 and 2017 at a tertiary hospital in Seoul, South Korea. As a control group, healthy participants were enrolled by mobile application recruitment. RESULTS: A total of 203 patients were enrolled for this study (PDAC, n = 102; healthy participants, n = 101). The peripheral blood NK cell activity of PDAC patients was significantly lower than that of healthy participants (median level, 95 pg/mL vs 2000 pg/mL, P < 0.001), and decreased NK cell activity was correlated to poor clinical outcome in terms of response to chemotherapy, tumor progression, and survival. The pro-inflammatory cytokine interleukin-6 had a strong negative correlation with NK cell activity. CONCLUSIONS: In pancreatic cancer patients, NK cell activity decreased as cancer progressed, and decreased NK cell activity was associated with poor clinical outcomes.

Radiographic portal or superior mesenteric vein invasion is an independent prognostic factor in non-metastatic pancreatic ductal adenocarcinoma: A missing block of clinical T staging?

BACKGROUND: Venous invasion is not included in the pancreatic ductal adenocarcinoma (PDAC) staging, and its correlation with prognosis remains unclear. We evaluated the prognostic impact of radiographic portal/superior mesenteric vein (PV/SMV) invasion, and its possibility of complementing T staging. METHODS: We identified patients with non-metastatic PDAC using our institutional cohort, and divided them according to PV/SMV invasion at imaging, defined as >180-degree tumor-vessel interface or contour deformity. We conducted Cox proportional hazard regression, and compared survival in the original and 1:1 propensity score matched datasets. RESULTS: We identified 454 patients [PV/SMV(+): 172; PV/SMV(-): 282]. In the multivariate analysis, PV/SMV invasion, age (≥70 years), performance status, tumor size (2-4, >4 cm), lymph nodes >4, and arterial invasion was correlated with prognosis. The PV/SMV(+) group had a shorter overall survival (OS) than the PV/SMV(-) group in the original (14.4 vs. 20.9 months; P < 0.001) and matched datasets (14.3 vs. 17.2 months; P = 0.009). Among patients without arterial invasion (cT1-cT3), the PV/SMV(+) group had a shorter OS (15.9 vs. 21.2 months; P = 0.002). Moreover, their OS did not differ from that of patients with arterial invasion (cT4) (15.9 vs. 14.4 months; P = 0.907). Patients with vessel (artery/vein) invasion had a shorter OS than those without vessel invasion (14.5 vs. 21.2 months; P < 0.001). CONCLUSIONS: Radiographic PV/SMV invasion in non-metastatic PDAC was correlated with a poor prognosis. It could identify a group with shorter OS among patients without arterial invasion (cT1-cT3). It is suggested that inclusion of PV/SMV invasion in clinical T4 criteria should be considered.

Clinical features and outcomes of hypertriglyceridemia-induced acute pancreatitis: Propensity score matching analysis from a prospective acute pancreatitis registry.

BACKGROUND: Hypertriglyceridemia (HTG) is a well-known cause of acute pancreatitis (AP) and elevation of serum triglycerides (TG) to ≥1000 mg/dl is strongly indicative of HTG-induced AP (HTG-AP). HTG-AP is potentially associated with persistent organ failure and poor prognosis. Here, we compared differences in clinical features and outcomes between patients with HTG-AP and patients with AP due to other causes. METHODS: A prospective AP registry was constructed in Gil Medical Center between June 2014 and May 2018. In total, 499 patients with AP were included for whom serum TG data at admission were available. RESULTS: HTG-AP was present in 52 patients (10.4%); these patients were younger than patients with AP due to other causes (39.62 ± 10.12 vs. 51.62 ± 17.41, p < 0.001). After propensity score matching adjusted by age, the factors associated with severity were more common in the HTG-AP group; these factors included the presence of systemic inflammatory response syndrome, Ranson's score ≥3, acute physiology, age, chronic health evaluation (APACHE) II score ≥8 at admission, and C-reactive protein level >10 mg/dl after 24 h of hospitalization. There were no significant differences in complications or severity based on the revised Atlanta classification 2012. In addition, recurrence was more frequent in the HTG-AP group (25.0% vs. 6.4%, p < 0.001). CONCLUSION: HTG-AP occurred in younger patients and showed more frequent recurrences than AP with other causes. Although factors related to severe feature were more common in HTG-AP during early phase, overall severity and prognosis were not different between the two groups.

Single-center risk factor analysis for FOLFIRINOX associated febrile neutropenia in patients with pancreatic cancer.

PURPOSE: FOLFIRINOX is the standard therapy in patients with unresectable pancreatic cancer (PC). However, FOLFIRINOX frequently induces febrile neutropenia (FN) and neutropenia. The purpose of this study was to explore risk factors for FN and grade 4 neutropenia (NP G4) in patients receiving FOLFIRINOX for PC. METHODS: We collected data on 106 patients with PC treated with first-line FOLFIRINOX between 2015 and 2017 using the Pancreatic Cancer Cohort Registry of Severance Hospital in Seoul, Korea. RESULTS: Multivariate logistic regression analysis showed that female (OR, 3.24; P = 0.023), Eastern Cooperative Oncology Group performance status (OR, 3.70; P = 0.024), overweight (OR, 4.25; P = 0.022), and initial biliary stent insertion (OR, 4.22; P = 0.008) were significantly related to a high risk of FN. Time-dependent bias was reduced using Cox regression analysis, which revealed that female (OR, 2.29; P = 0.041), overweight (OR, 2.67; P = 0.022), and initial biliary stent insertion (OR, 2.59; P = 0.016) were statistically significant predictors. Regarding NP G4, female sex (OR, 2.90; P = 0.016) and overweight (OR, 4.07; P = 0.033) were identified as risk factors in multivariate analysis; however, in Cox regression analysis, tumor in the head of the pancreas (OR, 1.96; P = 0.027) and hemoglobin (g/dL < 12) (OR, 1.87; P = 0.049) were also identified as risk factors. CONCLUSION: Female sex, overweight, and initial biliary stent insertion were independent risk factors for the occurrence of FN in patients with unresectable PC treated with FOLFIRINOX.

FOLFIRINOX vs gemcitabine/nab-paclitaxel for treatment of metastatic pancreatic cancer: Single-center cohort study.

BACKGROUND: FOLFIRINOX and gemcitabine plus nab-paclitaxel (Gem + nabPTX) were recently introduced for metastatic pancreatic cancer treatment. However, studies that compared these two regimens and studies in Asian populations are lacking. AIM: To compare the treatment outcomes of FOLFIRINOX and Gem + nabPTX regimen for metastatic pancreatic cancer treatment in Korean population. METHODS: Patients with metastatic or recurrent pancreatic cancer treated with FOLFIRINOX (n = 86) or Gem + nabPTX (n = 81) as the first-line since January 2015 were identified using the Severance Hospital Pancreatic Cancer Cohort Registry. Treatment efficacy, treatment-related adverse events and economic aspects were compared. RESULTS: Patients in the FOLFIRINOX group were significantly younger (54 vs 65 years; P < 0.001) and had better performance statuses at diagnosis. The median overall survival (10.7 vs 12.1 mo; P = 0.157), progression-free survival (8.0 vs 8.4 mo; P = 0.134), and objective response rates (33.7% vs 46.9%; P = 0.067) were not significantly different when compared with Gem + nabPTX group. Grade ≥ 3 neutropenia and gastrointestinal adverse events were more common in the FOLFIRINOX group. The drug costs of both regimens were similar. CONCLUSION: Treatment efficacy and economic burdens were comparable between the two regimens. But, the details of adverse event were different. Gem + nabPTX regimen might be considered preferentially in certain conditions.

Preoperative prediction of futile surgery in patients with radiologically resectable or borderline resectable pancreatic adenocarcinoma.

BACKGROUND AND AIM: The aim of this study is to identify the predictive factors for futile surgery in patients with radiologically resectable or borderline resectable pancreatic cancer and to develop a prediction model. METHODS: This retrospective study included patients who underwent pancreatic surgery for pancreatic cancer between 2006 and 2017. To identify independent risk factors for futile surgery, logistic regression and random forest analyses were performed in the training cohort, based on which a nomogram was established. The predictive accuracy and discriminative ability of the nomogram were validated in the validation cohort. RESULTS: Of 389 patients who underwent pancreatic surgery, the laparotomy was futile in 40 patients (10.3%). In the training cohort, the univariate and multivariate logistic regression analyses revealed that serum carbohydrate antigen 19-9 level of ≥ 150 U/mL (P = 0.003), the presence of suspicious lymph node (P = 0.013), and more extensive peripancreatic tumor infiltration (P < 0.001) were independent predictive factors for futile surgery. The bootstrap-corrected concordance index of the nomogram was high in the training cohort, 0.826 with a 95% confidence interval of 0.745-0.907. This model also showed a good discriminative performance in the validation cohort, with a concordance index of 0.831. CONCLUSIONS: We established and validated a novel nomogram that predicts the risk of futile surgery due to occult distant metastasis in patients with radiologically resectable or borderline resectable pancreatic cancer.

KML001, an arsenic compound, as salvage chemotherapy in refractory biliary tract cancers: A prospective study.

BACKGROUND: Sodium meta-arsenite (NaAsO2, KML001) is a potential oral anticancer agent acting on telomerase and telomere length. This prospective study evaluated its safety, tolerability, and effectiveness as salvage chemotherapy in patients with advanced biliary tract cancer (BTC) resistant to gemcitabine-based chemotherapy. METHODS: Forty-four patients (21 women and 23 men) with advanced BTC and failure history of gemcitabine-based chemotherapy, performance status (PS) 0-2, normal cardiac, hepatic, and renal function were enrolled. Daily dose of KML001 (7.5 mg. p.o.) was administered to eligible subjects for 24 weeks divided into six treatment cycles. Response was evaluated bimonthly using CT. RESULTS: After an average of 1.5 months of treatment (range: 0.5-10.0), 3 patients (6.8%) obtained progression-free status, 23 patients (52.3%) had disease progression, and 18 patients (40.9%) dropped out before evaluation. One patient (2.3%) completed six treatment cycles without progression. During the treatment, morphine dosage kept the same or decreased in 20 patients (47.6%). Nine patients (20.5%) experienced grade-3 adverse events (AEs), while no patient experienced grade-4 AEs. The most common AEs were liver enzyme elevation (11/44, 25%) and anemia (10/44, 22.7%). KML001 was discontinued in six patients (13.6%) due to AEs, including liver toxicity (n = 3), QTc prolongation (n = 2), and abdominal pain (n = 1). CONCLUSIONS: KML001 did not have enough anticancer effect on patients with advanced BTC resistant to gemcitabine. However, KML001 was safe and well-tolerable in terms of AEs and pain control when used as salvage therapy. Further studies are needed to establish arsenic agents as a reliable treatment option in patients with BTC.