Comparison of clinical/histological outcomes according to puncture sites in endoscopic ultrasound-guided fine needle biopsy for large pancreatic masses: Multicenter randomized prospective pilot study.

OBJECTIVES: There are no recommendations regarding the optimal puncture site in endoscopic ultrasound-guided fine needle biopsy (EUS-FNB). This multicenter randomized prospective study compared the diagnostic accuracy and histological findings according to the sampling site for pancreatic masses larger than 3 cm. METHODS: Consecutive patients with pancreatic masses larger than 3 cm indicated for EUS-FNB were included in the study. Patients were randomly assigned to two groups for the initial puncture site (central vs. peripheral sampling of the masses). A minimum of four passes were performed, alternating between the center and the periphery. The primary outcome was diagnostic accuracy. RESULTS: A total of 100 patients were equally divided into the central group and the peripheral group. The final diagnosis revealed malignancy in 95 patients (pancreatic cancer [n = 89], neuroendocrine tumor [n = 4], lymphoma [n = 1], metastatic carcinoma [n = 1]), and benign conditions in five patients (chronic pancreatitis [n = 4], autoimmune pancreatitis [n = 1]). There was no significant difference in diagnostic accuracy between the puncture sites. However, combining samples from both areas resulted in higher diagnostic accuracy (97.0%) compared to either area alone, with corresponding values of 88.0% for the center (P = 0.02) and 85.0% for the periphery (P = 0.006). CONCLUSIONS: Both central sampling and peripheral sampling showed equivalent diagnostic accuracy in detecting malignancy. However, combining samples from both areas generated superior diagnostic yield compared to using either sampling site alone. For pancreatic masses larger than 3 cm, it is advisable to consider sampling from various areas of the masses to maximize the diagnostic yield.

Liposomal irinotecan, oxaliplatin, and S-1 as first-line therapy for patients with locally advanced or metastatic pancreatic adenocarcinoma (NASOX): A multicenter phase I/IIa study.

INTRODUCTION: This multicenter phase I/IIa study aimed to determine the recommended phase II dose (RP2D) and evaluate the safety and preliminary efficacy of liposomal irinotecan (nal-IRI), oxaliplatin, and S-1 (NASOX) as first-line treatment for advanced pancreatic adenocarcinoma. METHODS: Patients with locally advanced or metastatic pancreatic adenocarcinoma without prior systemic treatment for advanced disease, aged ≥ 19 years, with measurable disease, and Eastern Cooperative Oncology Group performance status of 0-1 were eligible. The primary endpoints were to determine the dose-limiting toxicity (DLT) in the phase I cohort and overall response rate (ORR) in the phase IIa cohort. The intention-to-treat (ITT) analysis included patients who received the RP2D. RESULTS: In phase I, seven patients were screened, and six were assessed for DLT. None experienced DLT during the first cycle. The RP2D was determined as nal-IRI 50 mg/m2 and oxaliplatin 60 mg/m2 on day 1, S-1 40 mg/m2 twice daily on days 1-7 every 14 days. For the ITT (N = 41; 7, and 34 from phases I and IIa, respectively), the most common grade 3-4 treatment-emergent adverse events were neutropenia (31.7 %), enterocolitis (9.8 %), anorexia (7.3 %), and diarrhea (2.4 %). The ORR was 58.5 % (1 complete, and 23 partial responses). Two underwent conversion surgery; both achieved R0 resection. With median follow-up of 17.5 months, median progression-free survival was 6.5 months (95 % confidence interval [CI], 5.0-8.1) and median overall survival was 11.4 months (95 % CI, 9.8-15.5). CONCLUSION: NASOX exhibited a manageable safety profile and encouraging efficacy outcomes consistent with NALIRIFOX, showing potential to replace infusional 5-fluorouracil with oral S-1 in the triplet regimen.

Clinical Outcomes of Secondary Duodenal Self-Expandable Metallic Stenting for Duodenal Stent Dysfunction in Patients with Malignant Duodenal Obstruction: A Retrospective Multicenter Study.

Background/Aims: Malignant duodenal obstruction has become more common with the development of palliative therapies.The outcomes of endoscopic ultrasound-guided gastrojejunostomy (EUS-GJ) are comparable to those of surgical gastrojejunostomy or duodenal stenting. However, EUS-GJ is technically challenging. Duodenal self-expandable metallic stent (SEMS) placement is popular; however, obstructions are common. Duodenal SEMS obstruction can be managed with the insertion of a second SEMS in a stent-in-stent manner. Therefore, we aimed to analyze the clinical outcomes of secondary duodenal SEMS placement in patients with malignant duodenal obstruction. Methods: We retrospectively analyzed the data of patients who underwent secondary duodenal stent insertion for duodenal stent dysfunction between January 2016 and December 2021. The primary outcome was stent patency. The secondary outcomes were clinical success, factors associated with dysfunction, patient survival, and adverse events. Results: A total of 109 patients were included. The mean age was 64.4±11.2 years, and 63 patients (57.8%) were male. Ninety-two patients (84.4%) had pancreaticobiliary cancer. Clinical success was achieved in 94 cases (86.2%). Twenty-three patients experienced stent dysfunction with 231 days of median stent patency (95% confidence interval [CI], 169 to not available). After a multivariable Cox hazard analysis of stent patency, the Eastern Cooperative Oncology Group performance status (hazard ratio [HR], 2.13; 95% CI, 1.20 to 3.81; p=0.010) and the first stent patency ≥6 months (HR, 0.33; 95% CI, 0.11 to 0.95; p=0.050) remained significant associated factors. Adverse events occurred in five patients (4.6%). Conclusions: Secondary duodenal stent insertion is a viable option for first duodenal stent obstruction. Further comparative studies involving surgery or EUS-GJ for obstructed duodenal stents are warranted.

Long-term Outcomes of Ampullary Adenoma According to Resected Margin Status after Endoscopic Papillectomy.

Background/Aims: : Endoscopic papillectomy (EP) is increasingly used as an alternative to surgery for managing benign ampullary neoplasms. However, post-EP resection margins are often positive or indeterminate, and there is no consensus on the management of ampullary adenomas with positive or indeterminate margins after EP. This study was designed to compare the long-term outcomes between resected margin-negative (RMN) and resected margin-positive/indeterminate (RMPI) groups and to identify factors associated with clinical outcomes. Methods: : This retrospective analysis included patients with ampullary adenoma without evidence of adenocarcinoma who underwent EP between 2004 and 2016. The RMN and RMPI groups were compared for recurrence rates and recurrence-free duration during a mean follow-up duration of 71.7±39.8 months. Factors related to clinical outcomes were identified using multivariate analysis. Results: : Of the 129 patients who underwent EP, 82 were in the RMN group and 47 were in the RMPI group. The RMPI group exhibited a higher recurrence rate compared to the RMN group (14.6% vs 34.0%, p=0.019). However, the recurrence-free duration was not significantly different between the groups (34.7±32.6 months vs 36.2±27.4 months, p=0.900). Endoscopic treatment successfully managed recurrence in both groups (75% vs 75%). Submucosal injection was a significant risk factor for residual lesions (hazard ratio, 4.11; p=0.009) and recurrence (hazard ratio, 2.57; p=0.021). Conclusions: : Although ampullary adenomas with positive or indeterminate margins after EP showed a higher rate of recurrence at long-term follow-up, endoscopic treatment was effective with favorable long-term outcomes. Submucosal injection prior to resection was associated with increased risk of recurrence and residual lesions.

Long-Term Outcomes of Endoscopic Ultrasound-Guided Ablation Vs Surgery for Pancreatic Cystic Tumors.

BACKGROUND & AIMS: Endoscopic ultrasound-guided pancreatic cyst ablation (EUS-PCA) is performed as an alternative to surgical resection in selected patients with pancreatic cystic tumors (PCTs). We aimed to directly compare the long-term outcomes between EUS-PCA and surgery for PCTs. METHODS: We reviewed a PCT database to identify patients with unilocular or oligolocular PCTs who underwent EUS-PCA or surgery between January 2004 and July 2019. We performed 1:1 propensity score matching based on potential confounding factors. The primary outcome was long-term morbidities. Secondary outcomes included early (≤14 days) and late (>14 days) major adverse events (MAEs), development of diabetes mellitus, readmission, length of hospital stay, and therapeutic efficacy. RESULTS: A total of 620 patients (EUS-PCA, n = 310; surgery, n = 310) were selected after propensity score matching. The EUS-PCA group showed a lower 10-year rate of cumulative long-term morbidities (1.6% vs 33.5%; P = .001) as well as lower rates of early MAE (1.0% vs 8.7%; P = .001), late MAE (0.3% vs 5.5%; P = .001), and readmission (1.0% vs 15.2%; P = .001). The EUS-PCA group had a shorter hospital stay (3.5 vs 10.3 d; P = .001) and a lower incidence of diabetes mellitus (2.2% vs 22.8%; P = .001), whereas the surgery group had a higher complete resolution rate (76.5% vs 100%; P = .001) and a lower relapse rate (4.6% vs 0.3%; P = .001). CONCLUSIONS: For select patients with PCTs, EUS-PCA showed superior results to surgery in terms of long-term safety profile and preservation of pancreatic function.

Impact of the suprapapillary method on patency in distal malignant biliary obstruction: a multicenter randomized controlled trial.

BACKGROUND AND AIMS: Placement of a self-expandable metal stent (SEMS) across the duodenal major papilla carries a risk of duodenobiliary reflux (DBR). The suprapapillary method of stent placement may reduce DBR and improve stent patency compared with the transpapillary method. This study compared the clinical outcomes between the suprapapillary and transpapillary methods for distal malignant biliary obstruction (DMBO). METHODS: Between January 2021 and January 2023, consecutive patients with DMBO from 6 centers in South Korea were randomly assigned to either the suprapapillary arm or transpapillary method arm in a 1:1 ratio. The primary outcome was the duration of stent patency, and secondary outcomes were the cause of stent dysfunction, adverse events, and overall survival rate. RESULTS: Eighty-four patients were equally assigned to each group. The most common cause of DMBO was pancreatic cancer (50, 59.5%), followed by bile duct (20, 23.8%), gallbladder (11, 13.1%), and other cancers (3, 3.6%). Stent patency was significantly longer in the suprapapillary group (median, 369 days [interquartile range, 289-497] vs 154 days [interquartile range, 78-361]; P < .01). Development of DBR was significantly lower in the suprapapillary group (9.4% vs 40.8%, P < .01). Adverse events and overall survival rate were not significantly different between the 2 groups. CONCLUSIONS: The placement of SEMSs using the suprapapillary method resulted in a significantly longer duration of stent patency. It is advisable to place the SEMS using the suprapapillary method in DMBO. Further studies with a larger number of patients are required to validate the benefits of the suprapapillary method. (Clinical trial registration number: KCT0005572.).

Consensus statements on endoscopic ultrasound-guided tissue acquisition. Guidelines from the Asian Endoscopic Ultrasound Group.

OBJECTIVES: This consensus was developed by the Asian EUS Group (AEG), who aimed to formulate a set of practice guidelines addressing various aspects of endoscopic ultrasound-guided tissue acquisition (EUS-TA). METHODS: The AEG initiated the development of consensus statements and formed an expert panel comprising surgeons, gastroenterologists, and pathologists. Three online consensus meetings were conducted to consolidate the statements and votes. The statements were presented and discussed in the first two consensus meetings and revised according to comments. Final voting was conducted at a third consensus meeting. The Grading of Recommendations, Assessment, Development, and Evaluation system was adopted to define the strength of the recommendations and quality of evidence. RESULTS: A total of 20 clinical questions and statements regarding EUS-TA were formulated. The committee recommended that fine-needle biopsy (FNB) needles be preferred over conventional fine-needle aspiration (FNA) needles for EUS-TA of subepithelial lesions. For solid pancreatic masses, rapid on-site evaluation is not routinely recommended when FNB needles are used. For dedicated FNB needles, fork-tip and Franseen-tip needles have essentially equivalent performance. CONCLUSION: This consensus provides guidance for EUS-TA, thereby enhancing the quality of EUS-TA.

Comparison of long-term outcomes of endoscopic ultrasound-guided hepaticogastrostomy and choledochoduodenostomy for distal malignant biliary obstruction: a multicenter retrospective study.

Background: Endoscopic ultrasound-guided biliary drainage (EUS-BD), classified as choledochoduodenostomy (CDS) and hepaticogastrostomy (HGS), is a feasible and effective alternative for distal malignant biliary obstruction (MBO) in failed endoscopic retrograde cholangiopancreatography. However, the preferred technique for better outcomes has not yet been evaluated. Objectives: We compared the long-term outcomes between the techniques. Design: Retrospective comparative study. Methods: We reviewed consecutive patients who underwent EUS-CDS or EUS-HGS with transmural stent placement for distal MBO between 2009 and 2022. The primary outcome was the stent patency. The secondary outcomes were technical and clinical success, adverse events (AEs) of each technique, and independent risk factors for stent dysfunction. Results: In all, 115 patients were divided into EUS-CDS (n = 56) and EUS-HGS (n = 59) groups. Among them, technical success was achieved in 98.2% of EUS-CDS and 96.6% of EUS-HGS groups. Furthermore, clinical success was 96.4% in EUS-CDS and 88.1% in EUS-HGS groups, without significant difference (p = 0.200). The mean duration of stent patency for EUS-CDS was 770.3 days while that for EUS-HGS was 164.9 days (p = 0.010). In addition, the only independent risk factor for stent dysfunction was systematic treatment after EUS-BD [hazard ratio and 95% confidence interval 0.238 (0.066-0.863), p = 0.029]. The incidence of stent dysfunction of EUS-HGS was higher than EUS-CDS (35.1% versus 18.2%, 0.071), despite no significant differences even in late AEs. Conclusion: In distal MBO, EUS-CDS may be better than EUS-HGS with longer stent patency and fewer AEs. Furthermore, systematic treatment after EUS-BD is recommended for the improvement of stent patency.

Clinical outcomes of second-line therapy following disease progression on first-line modified FOLFIRINOX for borderline resectable and locally advanced pancreatic adenocarcinoma.

BACKGROUND: Modified FOLFIRINOX (mFOLFIRINOX) is one of the standard first-line therapies in borderline resectable pancreatic cancer (BRPC) and locally advanced unresectable pancreatic cancer (LAPC). However, there is no globally accepted second-line therapy following progression on mFOLFIRINOX. METHODS: Patients with BRPC and LAPC (n = 647) treated with first-line mFOLFIRINOX between January 2017 and December 2020 were included in this retrospective analysis. The details of the treatment outcomes and patterns of subsequent therapy after mFOLFIRINOX were reviewed. RESULTS: With a median follow-up duration of 44.2 months (95% confidence interval [CI], 42.3-47.6), 322 patients exhibited disease progression on mFOLFIRINOX-locoregional progression only in 177 patients (55.0%) and distant metastasis in 145 patients (45.0%). The locoregional progression group demonstrated significantly longer post-progression survival (PPS) than that of the distant metastasis group (10.1 vs. 7.3 months, p = 0.002). In the locoregional progression group, survival outcomes did not differ between second-line chemoradiation/radiotherapy and systemic chemotherapy (progression-free survival with second-line therapy [PFS-2], 3.2 vs. 4.3 months; p = 0.649; PPS, 10.7 vs. 10.2 months; p = 0.791). In patients who received second-line systemic chemotherapy following progression on mFOLFIRINOX (n = 211), gemcitabine plus nab-paclitaxel was associated with better disease control rates (69.2% vs. 42.3%, p = 0.005) and PFS-2 (3.8 vs. 1.7 months, p = 0.035) than gemcitabine monotherapy. CONCLUSIONS: The current study showed the real-world practice pattern of subsequent therapy and clinical outcomes following progression on first-line mFOLFIRINOX in BRPC and LAPC. Further investigation is necessary to establish the optimal therapy after failure of mFOLFIRINOX.

Endoscopic ultrasound-guided hepaticoduodenostomy versus percutaneous drainage for right intrahepatic duct dilatation in malignant hilar obstruction.

BACKGROUND AND AIM: Endoscopic ultrasound (EUS)-guided biliary drainage is being increasingly performed as an alternative to percutaneous transhepatic biliary drainage (PTBD) to treat malignant hilar obstruction (MHO) after failed endoscopic retrograde cholangiopancreatography (ERCP). However, no study has compared EUS-guided hepaticoduodenostomy (EUS-HDS) with PTBD for right intrahepatic duct (IHD) obstruction after failed ERCP in patients with unresectable MHO. METHODS: We retrospectively reviewed the data of consecutive patients with right IHD obstruction developed by unresectable MHO who underwent EUS-HDS or PTBD after a previous placement of a stent in the left and/or right IHD between March 2018 and October 2021. Technical success, clinical success, stent or tube-related adverse events, frequency of reintervention, and stent patency were evaluated. RESULTS: A total of 42 patients (18 EUS-HDS, 24 PTBD) were analyzed. Both groups did not show significant differences in technical success (EUS-HDS, 94% vs PTBD, 100%; P = 0.429), clinical success (83% vs 83%; P = 0.999), early adverse events (24% vs 46%; P = 0.144), and stent or tube-related late adverse events (29% vs 54%; P = 0.116). During follow-up, the EUS-HDS group had a longer median duration of patency (131 days vs 58.5 days; P = 0.041), and lower mean frequency of reinterventions per patient (0.35 vs 1.92; P = 0.030) than the PTBD group. CONCLUSIONS: EUS-HDS showed comparable efficacy and safety to PTBD for drainage of the right biliary system and produced longer duration of patency and lower frequency of reinterventions in patients with unresectable MHO.

Expanded indication for EUS-guided radiofrequency ablation: management of adrenal tumors.

BACKGROUND AND AIMS: EUS-guided radiofrequency ablation (EUS-RFA) has been performed as an alternative to surgery for the treatment of pancreatic tumors. The promising results obtained using this procedure suggest that the indication for EUS-RFA could be expanded to the management of extrapancreatic tumors. Here, we evaluate the feasibility, efficacy, and safety of EUS-RFA in the treatment of left adrenal tumors. METHODS: This single-center, prospective study was conducted at Asan Medical Center between January 2016 and November 2021. A total of 11 patients with left adrenal tumors were enrolled in the study. The technical success rate, treatment response, and adverse events were evaluated. RESULTS: EUS-RFA was performed successfully in all patients (technical success rate, 100%). The indications for the procedure were an increase in tumor size (n = 8), and adrenal tumor with adrenal hormone excess (n = 3). After a median of 2 EUS-RFA sessions (range, 1-2), 73% of patients had a complete response, and 27% had a partial response. During follow-up, 5 patients experienced self-limiting mild abdominal pain; no moderate or severe adverse events were reported. CONCLUSIONS: EUS-RFA showed high technical feasibility, clinical success, and an acceptable safety profile in the treatment of left adrenal tumors. In patients at high surgical risk, EUS-RFA can be considered as an alternative therapeutic modality to surgery for the treatment of left adrenal tumors.

Survival Benefit of Adjuvant Chemotherapy in Patients with Pancreatic Ductal Adenocarcinoma Who Underwent Surgery Following Neoadjuvant FOLFIRINOX.

PURPOSE: The benefit of adjuvant chemotherapy following curative-intent surgery in pancreatic ductal adenocarcinoma (PDAC) patients who had received neoadjuvant FOLFIRINOX is unclear. This study aimed to assess the survival benefit of adjuvant chemotherapy in this patient population. Materials and Methods: This retrospective study included 218 patients with localized non-metastatic PDAC who received neoadjuvant FOLFIRINOX and underwent curative-intent surgery (R0 or R1) between January 2017 and December 2020. The association of adjuvant chemotherapy with disease-free survival (DFS) and overall survival (OS) was evaluated in overall patients and in the propensity score matched (PSM) cohort. Subgroup analysis was conducted according to the pathology-proven lymph node status. RESULTS: Adjuvant chemotherapy was administered to 149 patients (68.3%). In the overall cohort, the adjuvant chemotherapy group had significantly improved DFS and OS compared to the observation group (DFS: median, 13.8 months [95% confidence interval (CI), 11.0 to 19.1] vs. 8.2 months [95% CI, 6.5 to 12.0]; p < 0.001; and OS: median, 38.0 months [95% CI, 32.2 to not assessable] vs. 25.7 months [95% CI, 18.3 to not assessable]; p=0.005). In the PSM cohort of 57 matched pairs of patients, DFS and OS were better in the adjuvant chemotherapy group than in the observation group (p < 0.001 and p=0.038, respectively). In the multivariate analysis, adjuvant chemotherapy was a significant favorable prognostic factor (vs. observation; DFS: hazard ratio [HR], 0.51 [95% CI, 0.36 to 0.71; p < 0.001]; OS: HR, 0.45 [95% CI, 0.29 to 0.71; p < 0.001]). CONCLUSION: Among PDAC patients who underwent surgery following neoadjuvant FOLFIRINOX, adjuvant chemotherapy may be associated with improved survival. Randomized studies should be conducted to validate this finding.

Long-term Outcomes of Endoscopic Intraductal Radiofrequency Ablation for Ampullary Adenoma with Intraductal Extension after Endoscopic Snare Papillectomy.

Background/Aims: There are limitations in treating ampullary adenomas with intraductal extension using conventional endoscopic modalities. Endoscopic intraductal radiofrequency ablation (ID-RFA) may be useful for treating intraductal (common bile duct [CBD] and/or pancreatic duct [PD]) extensions of ampullary adenomas, but long-term data are lacking. We thus evaluated the long-term outcomes of endoscopic ID-RFA for managing ampullary adenomas with intraductal extension. Methods: Prospectively collected endoscopic ID-RFA database at Asan Medical Center was reviewed to identify consecutive patients with ampullary adenoma who underwent ID-RFA for intraductal extension between January 2018 and August 2021. Technical success, short-term and long-term clinical success, and adverse events were evaluated. Results: A total of 29 patients (14 CBD, 1 PD, and 14 CBD and PD) were analyzed. All patients had undergone endoscopic snare papillectomy prior to ID-RFA. A median of one session of ID-RFA (range, 1 to 3) for residual or relapsed intraductal extension of ampullary adenoma were successfully performed (technical success=100%). Both biliary and pancreatic stenting were routinely performed after ID-RFA to prevent ductal stricture. After a median follow-up of 776 days (interquartile range, 470 to 984 days), the short-term and long-term clinical success rates were 93% and 76%, respectively. Seven patients experienced procedural adverse events and three patients developed ductal strictures. Conclusions: Endoscopic ID-RFA showed good long-term outcomes in treating residual or relapsed ampullary adenomas with intraductal extension. Repeated ID-RFA may be considered as an option for managing recurrence. Further studies are needed to standardize the procedure.

The usefulness of endobiliary radiofrequency ablation before metal stent placement in unresectable malignant hilar obstruction.

BACKGROUND AND AIM: EB-RFA with self-expandable metal stent (SEMS) may improve the stent patency and patient survival in malignant extrahepatic biliary obstruction. However, there are few studies on the role of EB-RFA for malignant hilar obstruction (MHO). This study aimed to assess the feasibility, efficacy, and safety of EB-RFA for MHO. METHODS: We retrospectively compared the stent patency and survival among 79 consecutive patients with MHO who underwent bilateral uncovered SEMS placement without and with EB-RFA between April 2016 and January 2020. RESULTS: Fifty-one patients (64.6%) underwent SEMS placement alone (stent alone group), whereas 28 (35.4%) underwent SEMS placement after EB-RFA (RFA-stent group). All procedures were successful (100%). During follow-up, stent occlusion occurred in 59 patients (74.7%), of which 40 (78.4%) and 19 (67.9%) were in the stent alone and RFA-stent groups, respectively. There was no difference in stent patency (192 ± 39.2 days vs 140 ± 53.7 days, P = 0.41) and survival (311 ± 24.7 days vs 311 ± 46.9 days, P = 0.73) between the stent alone and RFA-stent groups. Multivariate cox analysis showed a hazard ratio (HR) of 2.892 (1.579-5.294, P = 0.001) for stent occlusion in patients who did not receive chemotherapy. EB-RFA had no significant effect on stent occlusion (HR, 1.150, 0.644-2.053, P = 0.636). CONCLUSIONS: SEMS placement after EB-RFA in MHO was not associated with improvement in the stent patency or patient survival. Further prospective randomized studies are necessary to establish the effectiveness of EB-RFA with stents in MHO.

Real-world outcomes of adjuvant gemcitabine versus gemcitabine plus capecitabine for resected pancreatic ductal adenocarcinoma.

Background: Adjuvant chemotherapy is the standard treatment after curative-intent surgery for pancreatic ductal adenocarcinoma (PDAC). The phase-3 ESPAC-4 trial demonstrated significantly improved overall survival (OS) with Gemcitabine plus capecitabine (GemCap) over Gemcitabine (Gem) in Europe. We conducted a retrospective efficacy and safety evaluation of GemCap versus Gem in an Asian population. Methods: This retrospective analysis included 292 patients with PDAC who received adjuvant Gem or GemCap after curative resection between January 2017 and December 2020 at Asan Medical Center, Seoul, Korea. Results: Adjuvant Gem and GemCap were administered to 161 (55.1%) and 131 (44.8%) patients, respectively. The Gem group had significantly older patients (median 66 versus 63 years, p = 0.001); otherwise, the groups had similar baseline characteristics. With median follow-up durations of 39.4 [95% confidence interval (CI), 36.9-45.0] and 39.4 (95% CI, 34.7-41.6) months in the Gem and GemCap groups, the median OS was 36.8 (95% CI, 29.7-43.5) and 46.1 (95% CI, 31.5-not reached) months in the Gem and GemCap groups, respectively [unadjusted hazard ratio (HR) = 0.7; 95% CI, 0.5-1.0; p = 0.07). The median recurrence-free survival was 14.3 (95% CI, 12.9-17.7) and 17.0 (95% CI, 13.3-28.2) months, respectively (p = 0.5). Hand-foot skin reactions (any grade, 15.3% versus 0.6%; p < 0.001), neutropenia (78.6% versus 67.7%, p = 0.04) and thrombocytopenia (30.5% versus 20.5%, p = 0.04) were more common in the GemCap group. Multivariate analysis revealed adjuvant GemCap - compared with Gem - to be significantly associated with better OS (adjusted HR = 0.6; 95% CI, 0.4-0.9; p = 0.01). Otherwise, moderate or poor histological grade, lymph node positivity, positive resection margin, and elevated CA 19-9 (>median) were significantly associated with worse OS. Conclusions: Adjuvant GemCap showed the consistent clinical outcomes with the ESPAC-4 trial. As mFOLFIRINOX is the new standard treatment for medically fit patients with resected PDAC, further evaluation of optimal adjuvant chemotherapy in daily practice is warranted.

The Predicting Role of the Neutrophil-to-Lymphocyte Ratio for the Tumor Grade and Prognosis in Pancreatic Neuroendocrine Tumors.

This study aims to investigate the prognostic role of the neutrophil-to-lymphocyte ratio (NLR) in pancreatic neuroendocrine tumors (PNETs) using meta-analysis. This study evaluates the correlation between the NLR and the prognosis in PNETs from nine eligible studies. In addition, a subgroup analysis based on the tumor grade, treatment, and evaluation criteria, was conducted. The estimated rate of a high NLR was 0.253 (95% confidence interval (CI) 0.198-0.317). The rate of high NLRs was significantly lower in patients with lower tumor grades (G1) than those with higher tumor grades (G2 or G3). In addition, the mean value of the NLR was significantly lower in lower tumor grades than in higher tumor grades. High NLRs were significantly correlated with worse overall and recurrence-free survivals (hazard ratio (HR) 2.180, 95% CI 1.499-3.169 and HR 2.462, 95% CI 1.677-3.615, respectively). In a subgroup analysis, the prognostic implications of the NLR were found in both higher and lower criteria of a high NLR. Taken together, our results show that the NLR could be useful for predicting the tumor grade and the prognosis in PNETs.

Stereotactic Body Radiation Therapy versus Concurrent Chemoradiotherapy for Locally Advanced Pancreatic Cancer: A Propensity Score-Matched Analysis.

In locally advanced pancreatic cancer (LAPC), stereotactic body radiation therapy (SBRT) has been applied as an alternative to concurrent chemoradiotherapy (CCRT); however, direct comparative evidence between these two modalities is scarce. The aim of this study was to compare the clinical outcomes of SBRT with CCRT for LAPC. We retrospectively reviewed the medical records of patients with LAPC who received SBRT (n = 95) or CCRT (n = 66) with a concurrent 5-FU-based regimen between January 2008 and July 2016. The clinical outcomes of freedom from local progression (FFLP), progression-free survival (PFS), overall survival (OS), and toxicities were analyzed before and after propensity score (PS) matching. After a median follow-up duration of 15.5 months (range, 2.3-64.5), the median OS, PFS, and FFLP of the unmatched patients were 17.3 months, 11 months, and 19.6 months, respectively. After PS matching, there were no significant differences between the SBRT and CCRT groups in terms of the 1-year rates of OS (66.7% vs. 80%, p = 0.455), PFS (40.0% vs. 54.2%, p = 0.123), and FFLP (77.2% and 87.1%, p = 0.691). Our results suggest SBRT could be a feasible alternative to CCRT in treating patients with LAPC.

Granulocytic epithelial lesion (GEL) in heterotopic pancreas.

BACKGROUND: The diagnosis of type 2 autoimmune pancreatitis (AIP) is dependent on typical radiologic imaging and the presence of the granulocytic epithelial lesion (GEL), which is characterized by ductal neutrophilic infiltration with or without neutrophilic acinar infiltration. METHODS: We evaluated GEL and related clinicopathologic factors in 165 resected heterotopic pancreata (HPs) [57 gastric (35%), 56 duodenal (34%), 30 omental (18%), and 22 jejunal (13%)] and 29 matched orthotopic pancreata routinely examined during surgery. RESULTS: GEL was noted in 8% (13/165) of HPs, including ductal epithelial (6/13, 46%) and intraluminal (8/13, 62%) neutrophilic infiltrations. However, there was no GEL in orthotopic pancreata. Abdominal pain was observed in 6 (46%) patients with GEL-positive HPs. GEL was more commonly observed in HPs having symptoms (p = 0.029), a larger size (p = 0.028), and an infiltrative growth pattern (p = 0.006). In addition, periductal lymphoplasmacytic infiltration and fibrosis (both p < 0.001), interstitial fibrosis (p = 0.017), acinar neutrophilic infiltration (p = 0.032), venulitis (p = 0.050), acinar ductal metaplasia (ADM; p = 0.040), and pancreatic intraepithelial neoplasia/intraductal papillary mucinous neoplasms (PanIN/IPMN; p < 0.001) were more commonly seen in HPs with GEL than in those without GEL. Inflammatory bowel disease was present only in one patient with GEL-negative HP. CONCLUSIONS: GELs are detected in a subset of HPs without clinical evidence of AIP. Therefore, for the diagnosis of AIP, GEL should be carefully interpreted with the context of other histologic, clinical, and radiologic findings.

Clinical outcomes of EUS-guided radiofrequency ablation for unresectable pancreatic cancer: A prospective observational study.

BACKGROUND AND OBJECTIVES: EUS-guided radiofrequency ablation (EUS-RFA) has been increasingly used for the treatment of pancreatic neoplasms. The role of EUS-RFA in the management of pancreatic cancer has not yet been elucidated. This study aimed to evaluate the survival impact of EUS-RFA in unresectable pancreatic cancer. METHODS: Twenty-two patients (n = 14, locally advanced unresectable; n = 8, metastatic) with unresectable pancreatic cancer underwent EUS-RFA combined with subsequent chemotherapy between May 2016 and June 2019. Survival outcomes including overall survival (OS) and progression-free survival (PFS) were evaluated. RESULTS: EUS-RFA was successful in all patients. The median number of RFA sessions was 5 (interquartile range, [IQR], 3.25-5.75). After successful EUS-RFA, subsequent gemcitabine-based chemotherapy was performed. Early procedure-related adverse events occurred in 4 out of 107 sessions (3.74%), including peritonitis (n = 1) and abdominal pain (n = 3). During follow-up over a median of 21.23 months (IQR, 10.73-27.1), the median OS and PFS were 24.03 months (95% confidence interval [CI], 16-35.8) and 16.37 months (95% CI, 8.87-19), respectively. CONCLUSIONS: EUS-RFA is technically feasible and safe for the management of unresectable pancreatic cancer. EUS-RFA combined with systemic chemotherapy may be associated with favorable survival outcomes. Further larger-scale prospective comparative study is required to confirm these findings.

Clinical outcomes of EUS-guided transluminal drainage with a novel lumen-apposing metal stent for postoperative pancreatic fluid collection after pancreatic surgery.

BACKGROUND AND AIMS: EUS-guided transluminal drainage (EUS-TD) is increasingly used for the treatment of postoperative pancreatic fluid collections (POPFCs). A novel lumen-apposing metal stent (LAMS) was recently developed and used for the drainage of POPFCs. This study aimed to evaluate the efficacy and safety of a novel LAMS in patients with POPFCs. METHODS: Forty-seven patients with symptomatic POPFCs who underwent EUS-TD with a novel LAMS (Niti-S SPAXUS; Taewoong Medical Co, Ltd, Ilsan, South Korea) between April 2019 and July 2020 were included in this study. Clinical outcomes, including technical success, clinical success, and adverse events, were retrospectively evaluated. RESULTS: EUS-TD was technically successful in 41 of 47 patients (87.2%). Clinical success was achieved in 37 of 41 patients (90.2%). The mean procedure time was 13.7 ± 3.5 minutes. The mean POPFC size was 59 ± 18.9 mm. The mean time interval from surgery to EUS-TD was 24.2 ± 37.6 days. Five patients experienced 6 procedural adverse events (12.8%): 4 (8.5%) POPFC infections and 2 (4.3%) distal stent migrations. The 4 patients with POPFC infection underwent additional endoscopic interventions. Of the 2 patients with stent migration, 1 underwent laparoscopic exploration and surgical extraction of the stent and 1 (2.1%) experienced POPFC recurrence, which was managed with percutaneous drainage. CONCLUSIONS: EUS-TD for symptomatic POPFCs with a novel LAMS is technically feasible and effective, with an acceptable adverse event rate. Further larger-scale prospective studies are required to confirm the findings of this study.