Menghua Dai

Objectives: The objective of this study is to investigate the value of conventional ultrasound, contrast‐enhanced ultrasound (CEUS) and percutaneous ultrasound‐guided biopsy in the diagnosis of pancreatic metastases from clear cell renal cell carcinoma (ccRCC). Methods: A retrospective database search was conducted to identify all pancreatic lesions performed CEUS and final diagnosed as metastasis from ccRCC at our institution from September 2017 to June 2024. All enrolled patients were considered unsuitable for endoscopic ultrasound (EUS)‐guided tissue acquisition, had failed EUS‐guided biopsy, or required an alternative diagnostic approach. A total of 23 patients were enrolled in this study. Demographics, clinical features, ultrasound and CEUS findings, biopsy procedures, and results were collected and reviewed. Results: Of the enrolled patients, metachronous metastasis was 100%. The median interval time from tumor‐nephrectomy to the emergence of the pancreatic metastasis was 121.0 months (range: 46.0–276.0 months). Ultrasonography revealed rounded, well‐defined, homogeneous hypoechogenic lesions in all the patients. Color Doppler flow image findings displayed plenty of blood flow signals around and inside the pancreatic lesions in 87.0% of patients. 22 patients (95.7%) exhibited rapid hyper‐enhancement in the arterial phase of CEUS and 1 patient (4.3%) showed iso‐enhancement. In the venous phase, 15 cases showed sustained hyper‐enhancement and 8 cases showed iso‐enhancement. In the biopsy procedure, ultrasound‐guided core needle biopsy demonstrated higher diagnostic yield than fine needle aspiration (75.0% vs. 46.7%). The biopsy diagnosis was positive in 13 patients (65.0%) in general. Conclusions: Metastatic tumors of the pancreas can occur after a prolonged period from ccRCC diagnoses, thus long‐term follow‐up is necessary. The features of the lesion by conventional ultrasound and CEUS were specific, which are valuable for diagnosis. In patients who are unsuitable for EUS‐guided tissue acquisition or have experienced unsuccessful EUS‐guided sampling, CEUS combined with percutaneous ultrasound‐guided biopsy may serve as a valuable complementary second‐line diagnostic approach and facilitate accurate diagnosis.

Neoadjuvant therapy (NAT) has become the recommended treatment approach for patients with borderline resectable or locally advanced pancreatic cancer. Howe

Pancreatic ductal adenocarcinoma (PDAC) is characterized by a highly immunosuppressive and desmoplastic tumor microenvironment (TME) that limits the efficacy of immunotherapy. However, the evolution of this immunosuppressive TME and the underlying mechanisms remain incompletely understood. Here, we construct a dynamic single‐cell atlas spanning uninvolved adjacent pancreatic tissue (UNIN), intraductal papillary mucinous neoplasm (IPMN), and PDAC. We confirm the stepwise establishment of an immunosuppressive milieu, accompanied by the emergence of LRRC15 ⁺ fibroblasts as determinants. Functional assays further identify tumor‐derived LAMB3 as a regulator of LRRC15 ⁺ fibroblast differentiation. Mechanistically, LAMB3 promotes FOSL2‐dependent transcriptional activation of LRRC15 through the ITGB1/FAK/MAPK signaling axis, ultimately suppressing T cell cytotoxicity. Orthotopic models reveal that LAMB3 overexpression increases the LRRC15 positive area and impairs T cell cytotoxicity, whereas FAK inhibition partially reverses these effects. In parallel, LAMB3 knockdown reduces the LRRC15 positive area and improves the efficacy of PD‐1 blockade. Moreover, glycolytic reprogramming in PDAC ductal cells upregulates LAMB3 expression and correlates with increased LRRC15 ⁺ fibroblast enrichment. Clinically, co‐enrichment of LAMB3 ⁺ PDAC ductal cells and LRRC15 ⁺ fibroblasts is associated with inferior overall survival. Collectively, our findings define a dynamic ductal‐fibroblast‐immune multicellular axis underlying PDAC pathogenesis and provide insights into potential therapeutic strategies.

Robotic duodenum-preserving pancreatic head resection (R-DPPHR) is a technically feasible procedure for benign or borderline tumors of the pancreatic head. Among these, pancreatic cystic neoplasms (PCNs), particularly intraductal papillary mucinous neoplasms (IPMNs), are ideal candidates for this minimally invasive, organ-preserving approach. While numerous studies have demonstrated the short- and long-term advantages of DPPHR over conventional pancreaticoduodenectomy (PD), detailed video descriptions of the robotic-assisted procedure are scarce. This case report presents a step-by-step technical video of R-DPPHRt for a main duct-IPMN (MD-IPMN) in the pancreatic head. A 65-year-old male patient with upper abdominal discomfort was diagnosed with MD-IPMN, presenting as a 4.3 cm cystic-solid mass in the pancreatic head. R-DPPHRt was performed using the da Vinci Xi system, with an operation time of 350 minutes and an estimated blood loss of 150 mL. The patient had an uneventful postoperative course and was discharged on postoperative day 9. Pathology confirmed MD-IPMN with low-grade dysplasia. R-DPPHRt is an effective, function-preserving treatment for selected patients with pancreatic cystic neoplasms, particularly when performed by experienced surgeons in high-volume centers. While this single-case report limits generalizability, the article offers unique value by providing a clear procedural template.

Background: We aimed to determine the safety and effectiveness of minimally invasive (MI) vs. open (O) radical antegrade modular pancreatosplenectomy (RAMPS) in patients with distal pancreatic cancer. Advances in MI surgery have enhanced postoperative recovery, but the safety and oncological effectiveness of MI-RAMPS has not been validated. Materials and methods: A multicenter propensity score matching (PSM) study was conducted across eight centers in China from June 2020 to December 2023. Adults with resectable or borderline resectable distal pancreatic cancer who underwent MI-RAMPS or O-RAMPS were included. PSM was performed in a 1:1 ratio with a caliper width of 0.06. The primary outcome was the postoperative hospital stay (PHS). Secondary outcomes included R0 resection rates, postoperative complications, disease-free survival (DFS), and overall survival (OS). Results: Overall, 232 patients were included in the study (MI-RAMPS: 149, O-RAMPS: 83). Before matching, MI-RAMPS was associated with a lower rate of combined vascular resection (5.4% vs 14.5%, P = 0.018), fewer lymph nodes harvested (median 9 vs 13, P = 0.030), and a shorter PHS (median 9 vs 10 days, P = 0.013). After PSM, 69 patients were matched in each group. MI-RAMPS remained associated with a shorter PHS (median 9 vs 10 days, P = 0.005), with no significant differences in severe complication rates (2.9% vs 2.9%, P = 1.000), number of lymph nodes harvested (median 9 vs 12, P = 0.142), and R0 resection rate (95.7% vs 92.8%, P = 0.718). The MI-RAMPS group required a longer operative time (median 270 vs 240 min, P P = 0.316; median OS: 28.6 vs 34.3 months, P = 0.483). Conclusion: MI- RAMPS shortened PHS compared to O-RAMPS, with no difference in postoperative complications or oncologic outcomes, highlighting its feasibility for patients with distal pancreatic cancer.

Background: Lymph node metastasis (LNM) is a prognostic factor in pancreatic cancer. The association between the gut microbiota and LNM remains unexplored. This study aimed to characterize the gut microbiota and metabolomic profiles associated with LNM and to investigate their potential as predictive biomarkers. Methods: Fecal samples from pancreatic cancer patients undergoing surgery were analyzed using metagenomic sequencing and untargeted metabolomics. The patients were categorized into LNM and non-LNM (NLNM) groups. Differential microbiome taxa were analyzed using the DESeq2 package. Random forest predictive models were developed based on metagenomic and metabolomic data, with performance assessed using leave-one-out cross-validation (LOOCV). Results: A total of 26 patients with LNM and 29 patients without LNM were included. Principal coordinates analysis (PCoA) revealed significant differences in microbiota composition between the two groups (Anosim, p = 0.047). The absolute counts of Ruminococcus gnavus and Blautia wexlera were significantly decreased in LNM. Tryptophan-derived metabolites, indole-3-lactic acid (3-ILA) and indole-3-acrylic acid (3-IA), were downregulated in LNM. Functional pathway analysis showed downregulation of tryptophan metabolism in LNM, while cancer-related pathways were upregulated. Correlation analysis revealed a significant positive association between Ruminococcus gnavus and 3-ILA/3-IA levels. Moreover, Ruminococcus gnavus was positively correlated with CD8 ⁺ T cells. Predictive models based on the gut microbiota and metabolites distinguished LNM from NLNM, with AUC values of 0.854 and 0.940, respectively. Conclusion: The gut microbiota and metabolites exhibit significant alterations during lymph node metastasis in pancreatic cancer, especially Ruminococcus gnavus , Blautia wexlera , and tryptophan metabolites (3-ILA and 3-IA). Gut microbial and metabolite signatures may serve as potential non-invasive biomarkers for predicting LNM in pancreatic cancer. Further functional validation is required to determine whether and how the gut microbiota and metabolites may mediate lymph node metastasis.

Background Limited research has been conducted on the short-term outcomes comparing laparoscopic pancreaticoduodenectomy (LPD) and robotic pancreaticoduodenectomy (RPD), particularly in the post-learning curve stage. This study aims to investigate surgical efficacy and provide clinical practices for selecting suitable techniques between LPD and RPD. Methods A retrospective study was conducted on consecutive patients who underwent RPD and LPD between April 2016 and December 2023. Baseline characteristics, pathological information, and perioperative data were analyzed. Propensity score matching (PSM) analysis was performed to ensure the comparability of important factors between the groups. Results A total of 277 patients were enrolled in the study, of which 145 underwent RPD. Following PSM, 116 patients were included in each group and baseline characteristics were well matched. The RPD group demonstrated a lower conversion rate to laparotomy (5.2% vs. 18.1%, p = 0.002), reduced blood loss (350 vs. 500 ml, p = 0.031), and a higher rate of R0 resection (91.4% vs. 80.7%, p < 0.05) compared to the laparoscopic group. The incidence of B2-Grade postoperative pancreatic fistula (B2-POPF) was also lower in the RPD group compared to the LPD group (4.3% vs. 11.2%, p = 0.037). Among patients in the post-learning curve stage, perioperative outcomes were similar between the two groups. Conclusion RPD offered several advantages over LPD, including lower rates of conversion to open and blood loss, higher rates of R0 resection, and improved POPF outcomes. Other perioperative outcomes were comparable between the two groups. Both techniques appeared feasible and safe in experienced surgeons, though RPD was preferred in complex cases. Graphical Abstract

Significant gaps exist in understanding the gastrointestinal microbiota in patients with pancreatic cancer (PCA) versus benign or low-grade malignant pancreatic tumors (NPCA). This study aimed to analyze these microbiota characteristics and explore their potential use in distinguishing malignant pancreatic lesions. Between September 2020 and May 2024, fecal and oral samples were collected from 121 patients undergoing surgical resection or diagnostic biopsy of pancreatic lesions, including 75 patients with PCA and 46 patients with NPCA, and 16s rRNA sequencing was performed. Random forest models based using fecal and oral microbiota data were developed to diagnose PCA and NPCA, with performance assessed using the leave-one-out cross validation method. The Shannon index and PCoA analysis revealed significant differences in oral microbiota composition between PCA and NPCA (p < 0.001 and p = 0.001, respectively). Fecal microbiome richness differed significantly (p = 0.02), though composition similarity was noted (p = 0.238). LEfSe identified 16 and 23 genera with significant differences in fecal and oral microbiomes, respectively. Random forest classifiers based on fecal and oral microbiota achieved areas under the curves (AUCs) of 89.4% and 96.3%, respectively, for distinguishing PCA and NPCA. In the mucinous tumor cohort, oral and fecal microbiome classifiers outperformed CA19-9, yielding AUCs of 83.0% and 85.2%, respectively. Fecal and oral microbiota compositions were significantly different between PCA and NPCA patients. Random forest classifiers utilizing fecal and oral microbiota data effectively distinguish between benign or low-grade malignant and malignant pancreatic lesions.