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.

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.

Analytical Method Development and Dermal Absorption of 4-Amino-3-Nitrophenol (4A3NP), a Hair Dye Ingredient under the Oxidative or Non-Oxidative Condition.

The chemical 4-amino-3-nitrophenol (4A3NP) is classified as an amino nitrophenol and is primarily utilized as an ingredient in hair dye colorants. In Korea and Europe, it is exclusively used in non-oxidative or oxidative hair dye formulations, with maximum allowable concentrations of 1% and 1.5%, respectively. Despite this widespread use, risk assessment of 4A3NP has not been completed due to the lack of proper dermal absorption data. Therefore, in this study, both the analytical method validation and in vitro dermal absorption study of 4A3NP were conducted following the guidelines provided by the Korea Ministry of Food and Drug Safety (MFDS). Before proceeding with the dermal absorption study, analytical methods were developed for the quantitation of 4A3NP through multiple reaction monitoring (MRM) via liquid chromatography-mass spectrometry (LC-MS) in various matrices, including swab wash (WASH), stratum corneum (SC), skin (SKIN, comprising the dermis and epidermis), and receptor fluid (RF). These developed methods demonstrated excellent linearity (R2 = 0.9962-0.9993), accuracy (93.5-111.73%), and precision (1.7-14.46%) in accordance with the validation guidelines.The dermal absorption of 4A3NP was determined using Franz diffusion cells with mini-pig skin as the barrier. Under both non-oxidative and oxidative (6% hydrogen peroxide (H2O2): water, 1:1) hair dye conditions, 1% and 1.5% concentrations of 4A3NP were applied to the skin at a rate of 10 µL/cm2, respectively. The total dermal absorption rates of 4A3NP under non-oxidative (1%) and oxidative (1.5%) conditions were determined to be 5.62 ± 2.19% (5.62 ± 2.19 µg/cm2) and 2.83 ± 1.48% (4.24 ± 2.21 µg/cm2), respectively.

Comparison of the different versions of NCCN guidelines for predicting margin-negative resection of pancreatic cancer in patients undergoing upfront surgery.

OBJECTIVES: The purpose of this study was to compare the different versions of the National Comprehensive Cancer Network (NCCN) guidelines for defining resectability of pancreatic ductal adenocarcinoma (PDAC) in predicting margin-negative (R0) resection, and to assess inter-reader agreement. METHODS: This retrospective study included 283 patients (mean age, 65.1 years ± 9.4 [SD]; 155 men) who underwent upfront pancreatectomy for PDAC between 2017 and 2019. Two radiologists independently determined the resectability on preoperative CT according to the 2017, 2019, and 2020 NCCN guidelines. The sensitivity and specificity for R0 resection were analyzed using a multivariable logistic regression analysis with generalized estimating equations. Inter-reader agreement was assessed using kappa statistics. RESULTS: R0 resection was accomplished in 239 patients (84.5%). The sensitivity and specificity averaged across two readers were, respectively, 76.6% and 29.5% for the 2020 guidelines, 74.1% and 32.9% for the 2019 guidelines, and 72.6% and 34.1% for the 2017 guidelines. Compared with the 2020 guidelines, both 2019 and 2017 guidelines showed significantly lower sensitivity for R0 resection (p ≤ .009). Specificity was significantly higher with the 2017 guidelines (p = .043) than with the 2020 guidelines. Inter-reader agreements for determining the resectability of PDCA were strong (k ≥ 0.83) with all guidelines, being highest with the 2020 guidelines (k = 0.91). CONCLUSION: The 2020 NCCN guidelines showed significantly higher sensitivity for prediction of R0 resection than the 2017 and 2019 guidelines.

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.

Long-term outcomes of fully covered self-expandable metal stents for refractory biliary strictures after living donor liver transplantation: a retrospective study at a tertiary center.

BACKGROUND AND AIMS: Endoscopic multiple plastic stents are an established first-line treatment for anastomotic biliary stricture (ABS) management after liver transplantation (LT). Fully covered self-expandable metallic stents (FCSEMSs) have recently been used with favorable outcomes, but long-term treatment outcomes remain an issue for ABS. We evaluated the long-term outcomes of FCSEMS for the management of refractory ABS after LT. METHODS: We reviewed the prospectively collected and maintained endoscopic retrograde cholangiography database at Asan Medical Center to retrieve consecutive post-LT ABS cases that underwent an endoscopic FCSEMS placement between August 2009 and August 2019 after MPS placement failure. RESULTS: A total of 34 patients were enrolled in this study. Technical success had been achieved in all subjects (100%). The median stent placement duration was 3.1 months (IQR 2.7-6.1). Stricture resolution was achieved in 26 patients (clinical success 76.5%, 95% confidence interval 62-91). Early adverse events developed in 3 patients (8.8%), including distal stent migration. Late adverse events occurred in 9 patients (26.5%), including cholangitis (n = 7, 20.6%) and asymptomatic distal stent migration (n = 2, 5.9%). The median follow-up period was 57.9 months (IQR 51.9-64.3). Stricture recurrence occurred in 3 of 26 patients who achieved clinical success (11.5%). CONCLUSIONS: FCSEMS placement appears to be an effective and advisable intervention for refractory ABS as it can provide persistent stricture improvement over the long-term.

Evaluation of the Ejection Pressure for Tracking Internal Cracks during Compaction in Bilayer Tablet Formulations Using Experimental and Finite Element Methods.

This study aimed to evaluate the ejection pressure and the correlation of the findings with the occurrence of internal cracks within bilayer tablets (BLTs) consisting of metformin HCl (MF) and evogliptin tartrate (EG). Then, the mechanism of tablet failure was provided by the finite element method (FEM). The ejection pressure and the difference in diameter depending on MAIN-P were evaluated to understand the correlation between ejection pressure and change in the BLT internal structure. The ejection pressure and the difference in diameter increased as the MAIN-P increased, then steeply decreased from 350 MPa to 375 MPa of MAIN-P, despite there being no pattern in compaction breaking force and porosity. The mechanical integrity at the BLT interface was weakened by internal cracks, reducing ejection pressure. The stress distribution analysis during the compression revealed that crack formation caused by entrapped air located at the center of the BLT interface may not propagate due to concentrated stress, which promotes a tight bond at the edge of the BLT. Furthermore, complete delamination can occur in the ejection process due to localized and intensive shear stresses at the BLT interface. These findings indicate that the mechanisms of internal cracking and delamination were successfully confirmed by FEM simulation. Moreover, measuring ejection pressure before BLT manufacturing can prevent invisible tablet cracks without damaging the tablets.

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.

Impact of the Supra-papilla Method on Patency in Distal Malignant Biliary Obstruction: A Multicenter Randomized Controlled Trial.

BACKGROUND: /aims: Placement of a self-expandable metal stent (SEMS) across the duodenal major papilla carries a risk of duodenobiliary reflux (DBR). The supra-papilla method of stenting may reduce DBR and improve stent patency compared to the trans-papilla method. This study aimed to compare the clinical outcomes between the supra-papilla and trans-papilla methods for distal malignant biliary obstruction (DMBO). METHODS: Between January 2021 and January 2023, consecutive patients with DMBO from six centers in Korea were randomly assigned to either the supra-papilla or trans-papilla method arm in a 1:1 ratio. The primary outcome was the duration of stent patency, and secondary outcomes included the cause of stent dysfunction, adverse events, and overall survival rate. RESULTS: A total of 84 patients were equally assigned to each group. The most common cause of DMBO was pancreatic cancer (n=50, 59.5%), followed by bile duct (n=20, 23.8%), gallbladder (n=11, 13.1%), and other cancers (n=3, 3.6%). Stent patency was significantly longer in the supra-papilla group (median [95% confidence interval], 369 [289-497] vs. 154 [78-361] days; P < 0.01). Development of DBR was significantly lower in the supra-papilla group (9.4% vs 40.8%, P < 0.01). Adverse events and overall survival rate were not significantly different between the two groups. CONCLUSIONS: The placement of SEMS using the supra-papilla method resulted in a significantly longer duration of stent patency. It is advisable to place the SEMS using the supra-papilla method in DMBO. Further studies with a larger number of patients are required to validate the benefits of the supra-papilla method.

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.

The Effect of Compression Pressure on the First Layer Surface Roughness and Delamination of Metformin and Evogliptin Bilayer and Trilayer Tablets.

The objectives of this study were to evaluate the delamination of convex-shaped metformin HCl (MF) and evogliptin tartrate (EG) multi-layer tablets depending on the pre-compression and main compression pressures and simultaneously correlate these results with those of a surface roughness analysis. Free-flowing MF and EG (median diameters of 38.3 and 44.7 µm, respectively) granules prepared using the wet granulation method were pre-compressed and subsequently compressed into bilayer and trilayer tablets using a universal testing machine. The compaction force required to break the tablets increased linearly as the main compression pressure increased (30-150 MPa). Conversely, the interfacial strength and compaction breaking force decreased as the pre-compression pressure increased (10-110 MPa). A surface roughness analysis employing a profilometer revealed that the first layer (MF) roughness drastically decreased from 5.89 to 0.51 µm (Ra, arithmetic average of profile height deviations from the mean line) as the pre-compression pressure increased from 10 to 150 MPa in the bilayer tablet. Accordingly, the decrease in the roughness of the first layer reduced the inter-penetration at the interface, as observed via energy dispersive spectrometer (EDS)-equipped scanning electron microscopy, decreasing the interfacial bonding strength and causing delamination of the MF/EG multi-layer tablets. These findings indicate the significance of roughness control in the actual preparation of multi-layer tablets and the usefulness of profilometer- and EDS-based surface analyses for interpreting the delamination of multi-layer tablets.

EUS-guided radiofrequency ablation plus chemotherapy versus chemotherapy alone for pancreatic cancer (ERAP): An observational open-label pilot study.

Background: No study has compared EUS-guided radiofrequency ablation (EUS-RFA) plus systemic chemotherapy (CMT) with CMT alone for unresectable pancreatic ductal adenocarcinoma. Methods: This study compared the results of treatment in patients receiving EUS-RFA plus concomitant CMT (group A; n = 14) with those receiving CMT (group B; n = 14) as a pilot study. Results: From July 2017 to August 2018, 4 and 2 patients from groups A and B, respectively, withdrew from the study because of progression of the disease. In total, 10 and 12 patients from groups A and B, respectively, completed the study. All 30 EUS-RFA procedures were successful. Mean maximal tumor diameter before treatment of group A (n = 10) versus B (n = 12) was 62.2 ± 21.0 versus 50.5 ± 22.0 mm, respectively (P = not significant). After treatment, no statistically significant difference in mean maximal tumor diameter was found between both groups. However, in group B, mean maximal tumor diameter was significantly increased from 50.5 ± 22.0 to 56.3 ± 18.7 mm, respectively (P = 0.017). Tumor necrosis occurred in group A versus B at 10 of 10 (100%) versus 6 of 12 (50%) patients, respectively (P = 0.014). After treatment, group A patients could reduce the mean narcotic pain drug dosage at 26.5 mg of morphine equivalent per day (from 63.6 to 37.1 mg, P = 0.022), whereas group B patients could not reduce the dosage of pain-controlled medication. No statistically significant difference in 6-month mortality rate was found. In group A, 1 procedure-related nonsevere adverse event (n = 1 of 30 [3.3%]) occurred in 1 patient (n = 1 of 14 [7.1%]). Conclusions: In this study, the mean tumor diameter of group B was significantly increased after the treatment. Group A had a significantly higher rate of necrosis of tumor and required less narcotic.

Endoscopic Interventions in Pancreatic Cystic Neoplasms.

During the past two decades, there has been a significant evolution in endoscopic interventions in pancreatic cystic neoplasms (PCNs), ranging from diagnostic intervention (endoscopic ultrasound-guided through-the-needle biopsy [EUS-TTNB]) to therapeutic intervention (endoscopic ultrasound-guided pancreatic cystic ablation [EUS-PCA]). They have received attention as alternatives to conventional diagnostic and therapeutic modalities. EUS-TTNB can categorize PCN types accurately by providing histologic diagnoses that conventional diagnostic modalities cannot provide. As pancreatectomy entails high morbidities, EUS-PCA can be performed safely to treat PCNs in patients who refuse surgery or have high surgical risks.

Prediction of skin sensitization using machine learning.

As global awareness of animal welfare spreads, the development of alternative animal test models is increasingly necessary. The purpose of this study was to develop a practical machine-learning model for skin sensitization using three physicochemical properties of the chemicals: surface tension, melting point, and molecular weight. In this study, a total of 482 chemicals with local lymph node assay results were collected, and 297 datasets with 6 physico-chemical properties were used to develop Random Forest (RF) model for skin sensitization. The developed model was validated with 45 fragrance allergens announced by European Commission. The validation results showed that RF achieved better or similar classification performance with f1-scores of 54% for penal, 82% for ternary, and 96% for binary compared with Support Vector Machine (SVM) (penal, 41%; ternary, 81%; binary, 93%), QSARs (ChemTunes, 72% for ternary; OECD Toolbox, 89% for binary), and a linear model (Kim et al., 2020) (41% for penal), and we recommend the ternary classification based on Global Harmonized System providing more detailed and precise information. In the further study, the proposed model results were experimentally validated with the Direct Peptide Reactivity Assay (DPRA, OECD TG 442C approved model), and the results showed a similar tendency. We anticipate that this study will help to easily and quickly screen chemical sensitization hazards.

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 clinical outcomes of a fully covered self-expandable metal stent for refractory pancreatic strictures in symptomatic chronic pancreatitis: An 11-year follow-up study.

BACKGROUND AND AIMS: A fully covered self-expandable metal stent (FCSEMS) has recently been applied in the management of chronic pancreatitis patients with pancreatic strictures. However, related long-term effects remain unclear. This study aimed to evaluate the long-term outcomes of FCSEMS placement in chronic pancreatitis patients with refractory strictures. METHOD: We retrospectively reviewed our database for patients undergoing FCSEMS placement for refractory pancreatic strictures between September 2008 and December 2010. The main outcomes were technical, radiological, and clinical success, as well as recurrence and adverse events. RESULTS: A total of 35 patients were included. Technical success was achieved in all patients. The median FCSEMS indwelling time was 3.2 months (interquartile range [IQR], 3.0-4.9 months). Radiological success was achieved in all patients (complete, n = 2; partial, n = 33). Clinical success was achieved in 29 patients (82.9%; complete analgesic cessation, n = 19; analgesic reduction >50%, n = 11). During the median follow-up of 136 months, (IQR, 85.8-145.5 months), eight patients (22.9%) experienced recurrence. The median interval from stent removal to recurrence was 24.9 months (IQR, 11.3-30.3 months). Biliary obstruction, an early adverse event, occurred in two patients (5.7%); the late adverse event stent-induced de novo stricture was observed in 17 patients (48.6%). CONCLUSIONS: Our findings suggest that an FCSEMS is effective for relieving refractory strictures in chronic pancreatitis. However, FCSEMSs were associated with stent-induced de novo strictures in nearly half of the patients. Prospective studies are required to further evaluate the long-term efficacy and safety of FCSEMSs in chronic pancreatitis.

Comparison of the long-term outcomes between proximal and distal IgG4-related sclerosing cholangitis: A multicenter cohort study.

BACKGROUND AND AIMS: Immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) is considered a biliary manifestation of IgG4-related diseases. However, there has been a controversy on the clinical outcomes according to the location of the involved bile duct. We therefore compared the clinical outcomes and long-term prognosis of IgG4-SC with proximal bile duct involvement (proximal IgG4-SC) and IgG4-SC with distal bile duct involvement (distal IgG4-SC). METHODS: We reviewed the data of patients with IgG4-SC that were prospectively collected at 10 tertiary centers between March 2002 and October 2020. Clinical manifestations, outcomes, association with autoimmune pancreatitis (AIP), steroid-responsiveness, and relapse of IgG4-SC were evaluated. RESULTS: A total of 148 patients (proximal IgG4-SC, n = 59; distal IgG4-SC, n = 89) were analyzed. The median age was 65 years (IQR, 56.25-71), and 86% were male. The two groups were similar in terms of jaundice at initial presentation (51% vs 65%; P = 0.082) and presence of elevated serum IgG4 (66% vs 70%; P = 0.649). The two groups showed significant differences in terms of steroid-responsiveness (91% vs 100%; P = 0.008), association with AIP (75% vs 99%; P = 0.001), and occurrence of liver cirrhosis (9% vs 1%; P = 0.034). During a median follow-up of 64 months (IQR, 21.9-84.7), the cumulative relapse-free survival was significantly different between the two groups (67% vs 79% at 5 years; P = 0.035). CONCLUSIONS: Relapse of IgG4-SC frequently occurred during follow-up. Proximal IgG4-SC and distal IgG4-SC had different long-term outcomes in terms of steroid-responsiveness, occurrence of liver cirrhosis, and recurrence. It may be advantageous to determine the therapeutic and follow-up strategies according to the location of bile duct involvement.

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.