Introduction

Cholecystectomy is a common procedure in hepatobiliary surgery, with iatrogenic injury often leading to biliary fistula. Laparoscopic subtotal cholecystectomy (LSC) is employed when achieving a critical view of safety is challenging, but it comes with a high complication rate, including bile leaks. Laparoscopic common bile duct exploration (LCBDE) with laparoscopic cholecystectomy (LC) is utilized for cholecystolithiasis complicated with common bile duct (CBD) stones. Handling the CBD incision during LCBDE involves two approaches: indwelling T-tube drainage and primary suture.

Aims & Methods

Our research explores routine extra-drainage with tip-split drainage tubes (TSDT) for LCBDE+LC and LSC to reduce postoperative biliary fistulas. Early inspection of the cystohepatic triangle determines the feasibility of achieving a critical view of safety. If unattainable, LSC is considered, with attempts at standard laparoscopic cholecystectomy. TSDT drainage is decided based on the identification of bile flow from the cystic duct orifice. For cases without bile flow, TSDT drainage alone is used. If bile flow is identified, a purse-string suture of the cystic duct is performed, followed by TSDT placement. The LCBDE approach involves a longitudinal incision matching the stone's diameter. Choledochoscope exploration is completed with absorbable sutures or T-tube placement based on inflammation or the likelihood of residual stones. The TSDT is then placed.

Results

Our study, spanning 350 cases over five years, showed a high TSDT success rate, with no postoperative ERCP or PTCD interventions required. A learning curve of 1 to 2 cases was observed. Out of 350 patients, 30 underwent LSC and 320 LCBDE, resulting in 17 postoperative biliary fistula cases. Twelve were Grade A with no change in clinical management, and five were Grade B requiring minimal adjustments. All Grade A cases resolved within a week, while Grade B cases lasted over a week. Follow-up continued until bile leakage disappeared before catheter removal, with no progression to Grade C or relaparotomy requirements.

Conclusion

Our innovative TSDT technique effectively reduces postoperative bile leaks after LSC and LCBDE. Although not previously reported, TSDT appears superior to routine extra-drainage, being less technically demanding and less risky. General surgeons can likely adopt TSDT widely for improved hepatobiliary surgery outcomes.

Introduction

Pancreatic ductal adenocarcinoma (PDAC) remains a challenge in oncology with an overall survival rate remaining about 10%. Surgery and adjuvant chemotherapy stands as only curative treatment options. Only a minority of patients are diagnosed with resectable disease. While traditional diagnostic modalities show limitations in detecting and monitoring pancreatic cancer, liquid biopsies is a relatively new, non-invasive and promising diagnostic method for early detection, molecular profiling, and observation. Despite previous published or ongoing research projects and studies, liquid biopsies and specifically cell-free DNA (cfDNA) alterations role in management of pancreatic cancer remains unverified.

Aims & Methods

The aim of our study was to evaluate the diagnostic value of liquid biopsies and alterations in cfDNA levels in patients with pancreatic cancer. This study was approved by the Kaunas Regional Bioethics Committee (Approval ID: BE-2-31). Patients with newly diagnosed and histologically confirmed pancreatic cancer and patients with chronic pancreatitis, admitted to the Department of Surgery at Lithuanian University of Health Sciences Hospital, Kaunas Clinics, between September 2022 and December 2023, and healthy volunteers (control group) were included. Blood samples were obtained from the patients before any treatment procedures commenced. cfDNA was extracted from the collected blood using the QIAmp Circulating Nucleic Acid Kit (Qiagen). The concentration and quality of the extracted cfDNA were determined using the Qubit™ 1X dsDNA High Sensitivity (HS) and Broad Range (BR) Assay Kits (ThermoFisher Scientific, Inc., Waltham, MA, USA). Mann-Whitney U-test and Kruskal-Wallis H-test were used to determine the differences in quantitative traits between the comparison groups, with results being presented in median (min – max). The predictive capability (diagnostic performance) of cfDNA to distinguish PDAC and chronic pancreatitis/healthy controls was investigated by means of the area under the ROC (Receiver-Operating Characteristics) curve (AUC).

Results

Sixty-five patients were included (47 patients with PDAC, 10 patients with chronic pancreatitis and 8 healthy controls). Levels of cfDNA were statistically significantly higher in PDAC patients (46.5 (4 - 768) ng/ml) compared to patients with chronic pancreatitis (23.4 (8.56 - 138.4) ng/ml) (p = 0.032) and healthy controls (19.75 (17.6 - 22.8) ng/ml) (p < 0.001). The cfDNA cut-off value distinguishing PDAC from chronic pancreatitis and healthy controls were determined to be 23,65 ng/ml (AUC = 0.716) and 22.9 ng/ml (AUC = 0.915), respectively. There were no differences in cfDNA levels concerning tumor localization, size, differentiation, spread, or survival rates (all p > 0.05).

Conclusion

Liquid biopsies and cfDNA level alterations offer promising opportunities for distinguishing pancreatic cancer from benign inflammatory diseases, such as chronic pancreatitis. However, additional experiments and studies are necessary for more comprehensive validation and clinical use.

Disclosure

This study was partially funded by Lithuanian University of Health Sciences Scientific fund and Lithuanian Future Biomedicine foundation.

Introduction

Many patients (pts) with ulcerative colitis (UC) do not achieve long-term remission with conventional therapies but are hesitant to switch to advanced therapies. Ozanimod (OZA) is an oral advanced therapy approved for the treatment of moderately to severely active UC. Durability of up to 3 years of continuous OZA treatment has been reported in the True North (TN) open-label extension (OLE).

Aims & Methods

The objective of the current analysis of the TN OLE was to assess the long-term durability of OZA treatment in pts who were inadequately controlled on conventional therapies at TN baseline. Advanced therapy–naive pts who were OZA clinical responders at TN Week 52 were grouped by baseline endoscopic disease activity as moderate (Mayo endoscopy subscore [MES]=2) or severe (MES=3). OZA efficacy (clinical remission, clinical response, corticosteroid (CS)-free remission, and endoscopic improvement) was evaluated at OLE W46 and OLE W94. Symptomatic clinical response (decrease from baseline in the combined 6-point rectal bleeding subscore [RBS] + stool frequency subscore [SFS] of ≥1 point and ≥30% and a decrease of ≥1 point in RBS or absolute RBS ≤1 point) and symptomatic clinical remission (RBS=0 and SFS ≤1 point [and decrease of ≥1 point from baseline SFS]) were assessed from OLE W5 to W94. All endpoints were assessed using observed case (OC) and nonresponder imputation (NRI) analyses.

Results

Of the 82 advanced therapy–naive pts who entered the OLE in clinical response after 52 wk of OZA treatment during TN, 45 had moderate baseline endoscopic disease and 37 had severe baseline endoscopic disease. Baseline demographic and clinical characteristics were generally similar across groups. Based on OC analysis, symptomatic clinical response and remission were observed in 100.0% and 90.5% of moderate pts, respectively, at OLE W5 and in 100.0% and 91.2% of severe pts, respectively, at OLE W5. Rates of symptomatic clinical response and remission were maintained through OLE W94. Rates of clinical remission, clinical response, CS-free remission, and endoscopic improvement at OLE W46 were similar in moderate and severe pts and were maintained through OLE W94 in the OC analysis (Table). Overall, the data followed similar patterns in the NRI analyses across endpoints.

Conclusion

Advanced therapy–naive pts who experienced disease progression on conventional therapies had sustained efficacy on OZA for up to 3 years. Baseline endoscopic disease activity did not affect the long-term durability of OZA responders. OZA may be an appropriate advanced therapeutic option for sustaining long-term symptomatic and clinical benefit in pts with UC after loss of response to conventional treatments.

Disclosure

This study was funded by Bristol Myers Squibb, Princeton, NJ, USA.
LPB: served as a speaker, consultant, and advisory board member for AbbVie, Amgen, Biogaran, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Ferring, Forward Pharma, Genentech, H.A.C. Pharma, Hospira/Pfizer, InDex Pharmaceuticals, Janssen, Lycera, Merck, Mitsubishi, Norgine, Samsung Bioepis, Sandoz, Takeda, Theravance, Tillotts, and Vifor.
MDL: received research funding from Pfizer and Takeda; consulted for AbbVie, Bristol Myers Squibb, Calibr, Eli Lilly, Genentech, Janssen, Pfizer, Prometheus, Roche, Salix, Takeda, Target RWE, and Theravance.
BS: consulted for AbbVie, Arena, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Falk Pharma, Galapagos, Janssen, Pfizer, Prometheus, and Takeda; received speaker fees from AbbVie, CED Service GmbH, Falk Pharma, Ferring, Janssen, Novartis, Pfizer, and Takeda.
PI: received lecture fees from AbbVie, Bristol Myers Squibb, Celgene, Celltrion, Falk Pharma, Ferring, Galapagos, Gilead, Janssen, MSD, Pfizer, Sandoz, Sapphire Medical, Shire, Takeda, Tillotts, and Warner Chilcott; received financial support for research from Celltrion, MSD, Pfizer, and Takeda; received advisory fees from AbbVie, Arena, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Eli Lilly, Genentech, Gilead, Hospira, Janssen, MSD, Pfizer, Pharmacosmos, Prometheus Biosciences, Roche, Samsung Bioepis, Sandoz, Takeda, Topivert, VH2, Vifor, and Warner Chilcott.
FC: received research support from Takeda; consulted for Arena, Celgene, GlaxoSmithKline, and Takeda.
AJ, HW, and MTO: employees and/or shareholders of Bristol Myers Squibb.
DTR: received grant support from Takeda; consulted for AbbVie, AltruBio, Aslan, Athos, Bellatrix, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Chronicles, ClostraBio, Connect BioPharma, EcoR1, Eli Lilly, Genentech/Roche, Gilead Sciences, Iterative Health, Janssen, Kaleido Biosciences, Pfizer, Prometheus Biosciences, Reistone, Seres, Syneos, Takeda, Target RWE, and Trellus Health.
BA: received research funding from Takeda; consulted for AbbVie, Bristol Myers Squibb, Eli Lilly, Janssen, Medtronic, Pfizer, Samsung Bioepis, and Takeda; lectured for AbbVie, Bristol Myers Squibb, Eli Lilly, Janssen, Pfizer, and Takeda.

Introduction

Endoscopic papillectomy (EP) for duodenal ampullary tumors is primarily performed for lesions confined to the papilla, particularly adenomatous changes. However, early complications such as bleeding (0-21.6%), pancreatitis (0-23.1%), and perforation (0-8.3%) occur at relatively high rates. Post-EP bleeding, due to anatomical characteristics of the ampulla of Vater, can be challenging to manage and may worsen, making it critical to identify factors associated with this complication to reduce its frequency.

Aims & Methods

The study aimed to investigate the factors associated with post-endoscopic papillectomy bleeding in patients with ampullary tumors. This study included 39 patients (39 lesions), excluding residual and accessory ampullary lesions, who underwent EP at our institution between March 2011 and October 2024. We evaluated univariate analysis and SHAP values based on tree-based models for several factors related to post-EP bleeding. Hyperparameters of each model were optimized by optuna, and those models were trained with the Python package scikit-learn (version 1.3.0).

Results

The cohort included 1 adenocarcinoma, 32 adenomas, 1 neuroendocrine neoplasm, and 5 cases of ampullary inflammation, with a mean age of 66.7 years (23 males, 16 females). Patient factors included: The American Society of Anesthesiologists (ASA) Physical Status Classification I/II/III in 5/21/13 participants, median Charlson Comorbidity Index (CCI) of 1 (range 0-7), 15 cases with a history of alcohol consumption, median Brinkman Index of 100 (range 0-1680), median total bilirubin of 0.7 mg/dL (range 0.2-2.1), median serum amylase of 80 IU/L (range 36-296), median platelet count of 198,000/μL (range 113,000-494,000), median PT-INR of 0.98 (range 0.86-1.14), median APTT of 28.7 seconds (range 23.0-39.4), median CEA of 1.9 ng/mL (range 0.3-12.8), and median CA19-9 of 7.7 U/mL (range 0.8-76.4). Antithrombotic agents were used in 4 participants (1 on low-dose aspirin, 1 on clopidogrel, and 2 on direct oral anticoagulants), and periampullary diverticula were observed in 3 cases. Median tumor size was 10.3 mm (range 2.0-45.0). Procedural factors included a median total procedure time of 56 minutes (range 23-230), with 36 cases receiving endoscopic biliary stenting and 38 cases receiving endoscopic pancreatic duct stenting. The electrosurgical units ICC200/VIO300D/VIO3 were used in 9/19/11 cases, respectively. Protease inhibitors were used in 9 participants, NSAID suppositories (25mg/50mg) in 5/24 cases, and local hemostatic measures included epinephrine spray in 8 cases, thrombin spray in 8 cases, and hemostatic peptide solutions in 5 cases. Clipping for ulcer after resection was performed in 33 cases. Post-EP bleeding within 30 days occurred in 12 cases (30.8%), including 9 moderate and 3 severe cases. Univariate analysis revealed that a history of alcohol consumption was significantly associated with post-EP bleeding (Odds ratio [OR] 2.33, 1.14-4.79, P = 0.02). Feature importance was evaluated using the mean absolute SHAP values across all participants. In the Random Forest model, the top contributing features were CA19-9 (mean |SHAP| = 0.026), CCI (mean |SHAP| = 0.024), and a history of alcohol consumption (mean |SHAP| = 0.023). In contrast, the XGBoost model identified tumor size (mean |SHAP| = 0.315), a history of alcohol consumption (mean |SHAP| = 0.244), and platelet count (mean |SHAP| = 0.198) as the most important features.

Conclusion

In our cohort, a history of alcohol consumption is a robust factor associated with post-endoscopic papillectomy bleeding.