Ampullary adenocarcinoma (AMPAC) is a rare and heterogeneous malignancy with markedly variable clinical outcomes, underscoring the urgent need for molecularly informed classification and personalized therapeutic strategies. Current AMPAC classification relies primarily on morphological and immunohistochemical criteria, which lack prognostic accuracy and fail to capture the underlying molecular and tumor microenvironment heterogeneity. In this study, we integrated bulk RNA sequencing, single-cell RNA sequencing (scRNA-seq), and clinicopathological data to elucidate the molecular architecture of AMPAC and introduced a transcriptomic-based molecular classification (AMS). The AMS categorized patients into two molecular subtypes: mesenchymal AMPAC (AMS-M) and classical AMPAC (AMS-C). The AMS-M demonstrated increased epithelial-mesenchymal transition (EMT) and stromal activation, correlating with basal-like subtypes associated with unfavorable prognosis. In contrast, AMS-C tumors exhibited metabolic and differentiation programs with relatively preserved immune infiltration. Importantly, we identified MUC16 as a pivotal biomarker specifically overexpressed in AMS-M tumors. MUC16 knockout markedly reversed EMT, attenuated invasive and migratory capacities, and restored chemosensitivity in both cell lines and their xenograft models. Collectively, our findings establish AMS as a prognostically and therapeutically informative molecular classification framework for AMPAC, unveil the critical role of the tumor microenvironment in AMPAC heterogeneity, and provide a translational foundation for precision oncology in this rare tumor.

Multifocal sporadic non-functional pancreatic neuroendocrine tumors (NF-PanNETs) are rare, and their molecular underpinnings remain poorly understood. This study performed whole-exome sequencing on 35 synchronous primary tumors from 9 patients to characterize somatic alterations, copy-number variations, and clonal evolution. We found that multifocality was an independent risk factor for early recurrence. Significant intertumoral genomic heterogeneity was observed, with high discordance in both SNVs and CNVs between lesions. Enrichment of ATRX/MEN1 mutations in multifocal cases suggested a potential link to multifocality. Clonal evolution analysis revealed two distinct patterns: independent tumorigenesis (often associated with germline mutations) and intra-pancreatic metastatic spread. MEN1 mutations were further associated with increased M2 macrophage infiltration. These findings highlight the substantial molecular heterogeneity in multifocal NF-PanNETs and underscore the need for comprehensive lesion profiling and tailored therapeutic strategies based on genomic evolution patterns.

Celiac axis stenosis (CAS) has been historically underappreciated in risk stratification for clinically relevant postoperative pancreatic fistula (CRPOPF). In this study, we aimed to investigate the role of CAS as an independent and clinically meaningful extrapancreatic predictor and assess its incremental value in established predictive models. Overall, 1214 consecutive pancreaticoduodenectomies were conducted between January 2021 and December 2023. Patients with available preoperative abdominal contrast-enhanced computed tomography images were identified for this outcome-based retrospective cohort study. The CAS rate was assessed retrospectively using sagittal reconstruction of arterial phases and classified into no (< 30

BACKGROUND:Severe delayed post-pancreatectomy hemorrhage (SDPPH) is a fatal complication classified into pseudoaneurysm rupture and non-pseudoaneurysm hemorrhage. This study analyzed their clinical characteristics and outcomes. METHODS:A retrospective multicenter cohort study was conducted on consecutive patients who underwent pancreatic resection between January 2014 and December 2023. All SDPPH cases included in the study were confirmed by digital subtraction angiography. RESULTS:Pseudoaneurysm rupture accounted for 47.3% (44/93) of SDPPH. Overall mortality was 29.0% (27/93), without significant difference between the pseudoaneurysm and non-pseudoaneurysm groups (p > 0.05). The hemorrhage sites differed significantly between groups, with the common hepatic artery and its branches (excluding gastroduodenal artery) being most frequent in the pseudoaneurysm group (15/44, 34.1%), versus other sites (including anastomosis, splenic artery, portal vein, superior mesenteric vein, and left gastric artery) in the non-pseudoaneurysm group (22/49, 44.9%). Intensive care unit stay was shorter in the pseudoaneurysm group (1.8 ± 3.9 days) than in the non-pseudoaneurysm group (5.3 ± 10.6 days; p = 0.040). The clinical hemostasis success was significantly higher in the pseudoaneurysm group (81.8%, 36/44) than in the non-pseudoaneurysm group (32.7%, 16/49; p < 0.001). CONCLUSION:Pseudoaneurysm rupture was associated with a better SDPPH prognosis than non-pseudoaneurysm hemorrhage. Heightened vigilance is warranted for rebleeding in non-pseudoaneurysm cases.

Background:Pancreatic cancer is one of the most lethal malignancies, with limited therapeutic options. In this exploratory trial, we aimed to evaluate the efficacy and safety of nanoparticle polymeric micellar paclitaxel (pm-Pac) combined with gemcitabine as first-line treatment for metastatic pancreatic cancer (mPC). Methods:Twenty-one patients with histologically or cytologically confirmed mPC were enrolled in this study. The primary endpoint was progression-free survival (PFS). Meanwhile, the secondary endpoints included the objective response rate (ORR), overall survival, disease control rate (DCR), duration of response (DOR), and safety of combination therapy. Results:The median PFS was 7.4 months (95% confidence interval [CI]: 5.4-9.4 months). The ORR and DCR were 52.4% (95% CI: 29.1%-75.7%) and 95.2% (95% CI: 85.3%-100%), respectively. Amongst patients who achieved partial response, the median DOR was 4.8 months (95% CI: 1.5-8.1 months). No treatment-related deaths were reported. Grade 3-4 adverse events (AEs) occurred in 81.0% of patients, with increased γ-glutamyltransferase levels (38.1%), neutropenia (33.3%), and leukocytopenia (28.6%) being the most frequent AEs. Low SERPINB3 and SERPINB4 expression was correlated with prolonged PFS, accompanied by the significant downregulation of gene sets involved in DNA replication, nonsense-mediated mRNA decay, and protein translation in long-PFS tumours. Tumour immune microenvironment analysis revealed that patients with short PFS had increased levels of common lymphoid progenitors and decreased populations of mature B and T lymphocytes. Conclusions:The combination of pm-Pac and gemcitabine as first-line therapy for mPC exhibited favourable tolerability and clinical efficacy. However, larger randomized-controlled trials are needed to validate these preliminary findings. Trial Registration:www.chictr.org.cn, ChiCTR2300078861.

BACKGROUND:Pancreatic cancer involving the portal vein and/or superior mesenteric vein (PV/SMV) requires pancreatectomy with venous resection (PVR). This study evaluated the long-term outcomes and related factors in patients undergoing upfront PVR. MATERIALS AND METHODS:A retrospective, single-center cohort study included patients who underwent upfront PVR over a period of five years. Survival outcomes and prognostic factors were assessed using Kaplan-Meier survival curves and multivariable regression analyses. RESULTS:Of 404 patients who underwent upfront PVR, the 30-day mortality rate was 1.2%, and the 90-day mortality rate was 3.7%. The median overall survival (OS) was 19.8 months (95% CI: 17.5-22.9), with 1-, 2-, and 3-year OS rates of 71.4%, 40.8%, and 23.2%, respectively. Multivariate analysis revealed that older age (>65 years), elevated preoperative CA19-9 levels (>200 UI/mL), poor tumor differentiation, and lack of adjuvant chemotherapy as predictors of decreased OS. Notably, radiological or pathological evidence of venous invasion was an independent predictor of poor survival while postoperative adjuvant treatment significantly improved OS in these individuals. CONCLUSIONS AND RELEVANCE:Venous invasion is an independent prognostic factor for poor survival in pancreatic cancer patients undergoing upfront PVR, and adjuvant chemotherapy contributes to an extend postoperative survival.

Objectives:The aims of the study were to elucidate the clinicopathological characteristics, imaging features, and surgical outcomes of patients with serous cystic neoplasms (SCNs) and to compare the features between microcystic (MiC) and macrocystic (MaC) SCNs.Materials and Methods:In this single-center retrospective study, information of patients with SCN between 2016 and 2022 at our institution was collected and analyzed.Results:A total of 105 patients with SCNs were identified, including 58 (55.2%) with MiC type and 47 (44.8%) with MaC type. Patient age and American Society of Anesthesiologists grade in the MiC group were significantly higher than those in the MaC group. The overall preoperative diagnostic accuracy was 7.6%, with no patients in the MaC group correctly diagnosed before surgery. In imaging examinations, almost all (97.1%) exhibited a lobulated pattern. Internal septation, honeycomb pattern, central scar, and calcification were common, with a significantly higher incidence in the MiC group. No in-hospital deaths occurred, and the incidence of major complications were comparable in both groups.Conclusions:Although many patients presented with typical imaging features, accurate diagnosis of SCN remained difficult. Except for older age and higher American Society of Anesthesiologists grade in the MiC group, there were no significant differences in the clinicopathological characteristics between MiC and MaC SCN patients.

This study aimed to compare the benefits and identify the best second-line treatment regimen for gemcitabine-refractory unresectable pancreatic cancers. This retrospective analysis included 144 patients with unresectable pancreatic cancer who underwent a gemcitabine-based regimen as the first-line treatment. 57, 37, and 50 patients received oxaliplatin-, irinotecan-based, and modified FOLFIRINOX (mFFX) regimens, respectively. The primary endpoint of this study was progression-free survival (PFS) and the secondary endpoints were overall survival (OS), response rate, and treatment-related toxicity. There were no significant differences in median PFS (mPFS) (4.6 months vs. 2.9 months, P = 0.627, HR = 1.128, 95

BACKGROUND:Radical antegrade modular pancreatosplenectomy (RAMPS) is a modified procedure with better margin resection and more lymph node harvest compared to standard distal pancreatectomy (SDP) in the treatment of pancreatic ductal adenocarcinoma (PDAC). The role of RAMPS regarding long-term survival has not been clearly defined owing to a lack of randomized controlled trials. The aim of this study was to compare long-term survival after RAMPS and SDP for patients with PDAC. METHODS:This single-center retrospective cohort study was conducted from November 2013 to December 2022. Consecutive patients with PDAC who underwent RAMPS and SDP were reviewed. Patients with the following characteristics were excluded: distant metastasis, tumor recurrence, and second primary malignancy. Propensity score matching (PSM) was used to balance differences in baseline patient characteristics between RAMPS and SDP groups. The primary outcome was the association between surgery type and overall survival (OS) assessed using Cox proportional hazards regression models. RESULTS:A total of 581 patients with PDAC (336 [57.8%] men, mean [SD] age, 64.8 [9.3] years) were analyzed. RAMPS (197 [33.9%]) was correlated with the higher frequencies of borderline resectable pancreatic cancer (68 [34.5%]), arterial resection (37 [18.8%]), T4 stage tumor (80 [40.6%]), nodal metastasis (117 [59.4%]), negative posterior margin (153 [77.7%]), and a greater number of lymph nodes harvested (median [IQR], 16 [11-21]). After balancing preoperative CA19-9 levels, adjuvant chemotherapy, histological grade, T stage, and nodal stage, 174 pairs of patients were identified in the PSM cohort. The median OS was 29.6 (interquartile range, 15.7-61.4) months and 27.0 (interquartile range, 14.7-51.5) months in RAMPS and SDP, respectively. RAMPS was not associated with a survival benefit relative to SDP (hazard ratio, 0.87; 95% CI, 0.64-1.19; and p = 0.38). No significant difference in OS was observed between patients with a negative anterior margin (adjusted hazard ratio, 0.72; 95% CI, 0.45-1.15, and p = 0.17) and without nodal metastasis (adjusted hazard ratio, 0.93; 95% CI, 0.54-1.61; and p = 0.79). CONCLUSION:RAMPS can obtain better oncological outcomes but is not associated with improved long-term survival compared with SDP. Regarding a negative anterior margin or without nodal involvement, RAMPS may be an optimal operation to strive for R0 resection.

e16382 Background: Pancreatic cancer remains one of the most lethal malignancies, characterized by limited therapeutic options. This Phase II clinical trial evaluated the efficacy and safety of nanoparticle polymeric micellar paclitaxel(pm-Pac) combined with gemcitabine as first-line treatment for metastatic pancreatic cancer(mPC). Methods: 21 patients with histologically or cytologically confirmed mPC were enrolled. Patients received pm-Pac intravenously at a dose of 230 mg/m² every 3 weeks and gemcitabine hydrochloride for injection at a dose of 1000 mg/m² on Days 1 and 8 of each 3-week cycle for eight cycles. The primary endpoint was progression-free survival(PFS), and the secondary endpoints included objective response rate (ORR), overall survival (OS), disease control rate (DCR), duration of response (DoR), and the safety of the combination therapy. Results: The median progression-free survival (mPFS) was 7.4 months (95% CI: 5.3-9.5). The ORR was 52.4% (95% CI: 29.1%-75.7%), and the DCR was 95.2% (95% CI: 85.3%-100%). Among patients who achieved a partial response, the median DoR was 5.0 months (95% CI: 3.0-6.9). The time to progression (TTP) was 7.4 months (95% CI: 5.3-9.5). There were no treatment-related deaths reported. Grade 3-4 adverse events (AEs) occurred in 81.0% of patients, with neutropenia (38.1%), neuropathy (14.3%), and anemia (9.5%) being the most frequent. Conclusions: In conclusion, the combination of pm-Pac and gemcitabine, as the first-line therapy for mPC, exhibited favorable tolerability and encouraging clinical efficacy. Larger randomized controlled trials are necessary to validate these preliminary findings. Clinical trial information: ChiCTR2300078861 .

PURPOSE:Pancreatic ductal adenocarcinoma (PDAC), known for its high fatality rate, is often diagnosed in its advanced stages where surgical options are not viable. This highlights the critical need for innovative and effective early detection techniques. This study focuses on the potential of cell-free DNA (cfDNA) fragmentomics integrating advanced machine learning to identify early-stage PDAC with high accuracy. METHODS:Our study included a broad cohort of 1,167 participants, from which plasma was collected and subjected to shallow whole-genome sequencing. After rigorous quality assessments, 166 individuals diagnosed with PDAC and 167 healthy participants were in the training cohort, whereas the validation cohort consisted of 112 patients with PDAC and 111 healthy individuals. A separate group of 67 individuals with nonmalignant pancreatic cysts was also included to validate the model's accuracy. Finally, two additional external validation cohorts and one additional independent early-stage data set were included to evaluate the robustness of model. Our analysis used fragmentomic profiling, integrating copy-number variations, fragment size, mutational signatures, and methylation patterns analyzed using machine learning. RESULTS:The model demonstrated remarkable accuracy in distinguishing patients with PDAC from controls, with an AUC of 0.992 in the training data set and 0.987 in the validation data set. At a cutoff of 0.52, the training set reached a sensitivity of 93.4% and a specificity of 95.2%. In the validation data set, the sensitivity was 97.3% with a specificity of 92.8%, while the external data set demonstrated a sensitivity of 90.91% and a specificity of 94.5%. CONCLUSION:This study underscores the effectiveness of using cfDNA fragmentomics and machine learning for early detection of PDAC. Our approach promises significant potential in reducing PDAC mortalities through early intervention and could serve as a breakthrough in oncologic diagnostics.

Backgrounds/Aims:Distal pancreatectomy with splenectomy (DPS) is a common surgical procedure for pancreatic body cancer. However, spleen-preserving distal pancreatectomy (SPDP) utilizing the Warshaw technique (WT) in malignancies is generally not favored due to concerns about inadequate resection. This study aims to assess the feasibility and oncologic outcomes of employing SPDP with WT in pancreatic body cancer. Methods:We conducted a retrospective analysis comparing 21 SPDP patients with 63 DPS patients matched by propensity score from January 2018 to November 2022. Clinical outcomes and follow-up data were analyzed using R. Results:Both groups exhibited similar demographic, intraoperative, and pathological characteristics, with the exception of a reduced number of total lymph nodes (p = 0.006) in the SPDP group. There were no significant differences in the rates of postoperative complications, recurrence, or metastasis. Local recurrence predominantly occurred in the central region as opposed to the spleen region. There were no cases of isolated recurrences in the splenic region. Median overall survival and recurrence-free survival times were 51.5 months for SPDP vs 30.5 months for DPS and 18.7 months vs 16.8 months, respectively (p > 0.05). The incidence of partial splenic infarction and left-side portal hypertension in the SPDP group was 28.6% (6/21) and 9.5% (2/21), respectively, without necessitating splenic abscess puncture, splenectomy, or causing bleeding from perigastric varices. Conclusions:SPDP did not negatively impact local recurrence or survival rates in selected pancreatic body cancer patients. Further studies are necessary for validation.

Postpancreatectomy hemorrhage (PPH) is a severe complication in pancreatic surgery. This study focused on early PPH (E-PPH), aiming to identify its characteristics, evaluate the existing grading criteria by the International Study Group of Pancreatic Surgery (ISGPS), and explore effective treatment strategies. Patients undergoing pancreatic surgery between March 2020 and January 2024 in two institutions were screened from prospectively maintained databases. Patients with E-PPH were divided into intervention group and the conservative group. The sites of hemorrhage were determined and categorized. Clinical presentation and outcomes were compared among different grades and interventions. Among 4062 patients who underwent pancreatic surgery, 113 cases of E-PPH were identified, with an incidence of 2.8

Pancreatic cancer is a highly malignant tumor of the digestive system and has an extremely poor prognosis. Due to its insidious onset and rapid progression, major surrounding vessels are frequently invaded at the time of diagnosis. Consequently, resection and reconstruction of the portal vein and/or superior mesenteric vein are often required during pancreatectomy. Various methods of venous resection and reconstruction have been developed, each with its own advantages, limitations, and specific applicability. Compared with open surgery, laparoscopic pancreatectomy requires higher technical proficiency and more precise intraoperative decision-making. To promote the advancement of venous reconstruction techniques in laparoscopic pancreatectomy, in this article, we summarize and evaluate our team's practical experience and relevant literature, focusing on graft selection, technical difficulty, operative risk, and short- and long-term patency. Special emphasis was placed on the applicability of different approaches and materials. In addition, regarding postoperative reconstruction of venous patency, we introduced the "Cross-sectional Area Algorithm", a method simulating the evaluation mode of coronary artery patency, to accurately quantify postoperative venous patency. The evaluation method was first proposed by the team but has not yet been externally validated. By reviewing the current status of venous reconstruction strategies and the prognosis of laparoscopic pancreatic surgery, we aim to inform the development of standardized technical guidelines, enable individualized assessment of venous patency after surgery, and ultimately improve minimally invasive pancreatic surgery and the long-term prognosis of patients.

Background Concomitant venous resection during pancreatectomy for pancreatic space-occupying lesions with veinous involvement is increasingly performed to achieve oncological resection. This study aims to report a single-center experience in peritoneal patch graft for vascular reconstruction during laparoscopic pancreatectomy. Methods A retrospective analysis of all 6 patients who underwent laparoscopic pancreatectomy as well as the venous reconstruction with autologous peritoneum graft were compared with the control group, 8 patients who received Laparoscopic pancreaticoduodenectomy with venous resection and primary anastomosis. Postsurgical complications and outcomes were evaluated. We specifically assessed the reconstructed venous patency ratio by Cross-sectional Area Algorithm which was based on post-surgical CT-Venograms, thereafter the overall patency ratio was compared with the control group. Results All 6 patients underwent venous resection and reconstruction using peritoneum patches of appropriate size, which includes 5 cases of lateral patch repairing and 1 case of tubular repairing. There are no significant differences noticed in post-surgical complications and outcomes between the peritoneum graft group and the control group. However, most of the peritoneum graft cases showed stenosis or complete occlusion after surgery. Partial venous stenosis or complete occlusion did not cause abnormal liver function as newly formed venous collaterals were early detected and progressively robust. Conclusions Use of peritoneal patch as a venous substitute during the laparoscopic pancreatectomy contains satisfied operability and safety. However, the post-surgical reconstructed venous patency was an issue that need to be noticed. Overall, the peritoneum repairing technique is a considerable choice that assisted the oncological resection in certain situations.

Racial and ethnic disparities persist in cancer survival rates across the United States, despite overall improvements. This comprehensive analysis examines trends in 5-year relative survival rates from 2002-2006 to 2015-2019 for major cancer types, elucidating differences among racial/ethnic groups to guide equitable healthcare strategies. Data from the SEER Program spanning 2000-2020 were analyzed, focusing on breast, colorectal, prostate, lung, pancreatic cancers, non-Hodgkin lymphoma, acute leukemia, and multiple myeloma. Age-standardized relative survival rates were calculated to assess racial (White, Black, American Indian/Alaska Native, Asian/Pacific Islander) and ethnic (Hispanic, Non-Hispanic) disparities, utilizing period analysis for recent estimates and excluding cases identified solely through autopsy or death certificates. While significant survival improvements were observed for most cancers, notable disparities persisted. Non-Hispanic Blacks exhibited the largest gain in breast cancer survival, with an increase of 5.2% points (from 77.6 to 82.8%); however, the survival rate remained lower than that of Non-Hispanic Whites (92.1%). Colorectal cancer survival declined overall (64.7-64.1%), marked by a 6.2% point drop for Non-Hispanic American Indian/Alaska Natives (66.3-60.1%). Prostate cancer survival declined across all races, with Non-Hispanic American Indian/Alaska Natives showing a decrease of 7.7% points (from 96.9 to 89.2%). Lung cancer, acute leukemia, and multiple myeloma showed notable increases across groups. Substantial racial/ethnic disparities in cancer survival underscore the notable need for tailored strategies ensuring equitable access to advanced treatments, particularly addressing significant trends in colorectal and pancreatic cancers among specific minority groups. Careful interpretation of statistical significance is warranted given the large dataset.

BACKGROUND:Marginal ulcer (MU) is one of the postoperative complications of pancreaticoduodenectomy (PD), which needs particular attention in postoperative treatments. METHODS:The data of 190 patients who underwent PD and follow-up gastroscopic review due to upper GI symptoms within two years were retrospectively analyzed. The incidence of MU and risk factors were analyzed based on personal history, surgical procedure, past medical history, postoperative complications, and other relevant indicators. RESULTS:The proportion of MU in patients who underwent endoscopic follow-up for upper gastrointestinal symptoms in the postoperative period in this cohort was 10.5% (20/190). Advanced age (69y vs. 59y, P ​= ​0.012), alcohol consumption (20% vs. 8.2%, P ​= ​0.03), and cigarette smoking (35% vs. 14.7%, P ​= ​0.022) were associated with an increased incidence of MU. Longer surgery time (276.5min vs. 240min, P ​= ​0.049), postoperative bleeding (10% vs. 1.8%, P ​= ​0.030), and failure to take antacid regularly postoperatively (75% vs. 97.1%, P ​= ​0.000) would increase the risk of MU; taking antacid regularly was an independent protective factor for postoperative anastomotic ulceration (OR: 0.091, CI: 0.022-0.383, P ​= ​0.001). CONCLUSION:Advanced age, alcohol consumption, smoking, longer operation time, or postoperative extraluminal hemorrhage are associated with MU. Regular use of antacids is an independent protective factor against the development of MU.

4173 Background: Pancreatic ductal adenocarcinoma (PDAC) is one for the most lethal types of cancer. Nearly 80% of the PDAC patients are diagnosed at advanced unresectable stages. Therefore, an accurate early diagnosis assay is urgently needed for reducing PDAC related mortalities. In this study, we aim to utilize cfDNA fragmentomics and machine learning techniques for sensitively detecting PDAC patients. Methods: Total647 cases were prospectively enrolled in this study. Plasma samples were collected from each participant for shallow WGS (~5X). After quality control process, 166 PDAC patients and 167 healthy controls were enrolled as a training cohort. Additional 112 PDAC patients and 111 healthy controls were included as an independent validation cohort. Additional 67 cases with pancreatic benign cystic tumors were also enrolled for model validation including IPMN (Intraductal papillary mucinous neoplasms), MCN (Mucinous cystic neoplasms) and SCN (Serous cystic neoplasms). Four fragmentomics profiles, including copy number variation, fragment size, mutation signatures, and FRAGmentomics-based Methylation Analysis (FRAGMA) were utilized by a machine learning algorithm for developing a predictive model. Results: The predictive model showed an exceptional performance to distinguish PDAC patients from healthy controls, yielding Area Under the Curve (AUC) of 0.993 in the training cohort (5-fold cross validation) and 0.990 in the validation cohort. In the training cohort, our model was capable of detecting PDAC patients at sensitivity of 95.8% and specificity of 95.2% while using 0.49 as cutoff. The validation cohort achieved 99.1% sensitivity at 91.0% specificity while applying the same cutoff. Conclusions: Our model was able to accurately detect PDAC at early stages, by incorporating fragmentomics features through machine learning. It can potentially be used for PDAC early screening, and therefore reducing PDAC related mortalities.