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Aim: Laparoscopic and endoscopic cooperative surgery for early non-ampullary duodenum tumors (D-LECS) is now noted because of its safety and lower invasiveness. Here, we introduce two distinct approaches (antecolic and retrocolic) according to the tumor location during D-LECS., Methods: From October 2018 to March 2022, 24 patients (25 lesions) underwent D-LECS. Two (8%), two (8%), 16 (64%), and five (20%) lesions were located in the first portion, in the second portion to Vater's papilla, around the inferior duodenum flexure, and in the third portion of the duodenum, respectively. The median preoperative tumor diameter was 22.5 mm., Results: Antecolic and retrocolic approaches were employed in 16 (67%) and 8 (33%) cases, respectively. LECS procedures, such as two-layer suturing after full-thickness dissection and laparoscopic reinforcement by seromuscular suturing after endoscopic submucosal dissection (ESD), were performed in five and 19 cases, respectively. Median operative time and blood loss were 303 min and 5 g, respectively. Intraoperative duodenal perforations occurred in three of 19 cases during ESD; however, they were successfully laparoscopically repaired. Median times until start diet and postoperative hospital stay were 4.5 and 8 days, respectively. Histological examination of the tumors revealed nine adenomas, 12 adenocarcinomas, and four GISTs. Curative resection (R0) was achieved in 21 cases (87.5%). In a comparison of the surgical short outcomes between antecolic and retrocolic approaches, there was no significant difference., Conclusion: D-LECS can be a safe and minimally invasive treatment option for non-ampullary early duodenal tumors, and two distinct approaches according to the tumor location are feasible., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The prediction of prognostic outcomes can provide the most suitable strategy for patients with pancreatic ductal adenocarcinoma (PDAC). This study aimed to evaluate the clinical value of the preoperative tumor marker index (pre-TI) in predicting prognostic outcomes after resection for PDAC., Methods: For 183 patients who underwent pancreatic resection of PDAC, adjusted carbohydrate antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA), pancreatic cancer-associated antigen-2 (DUpan-2), and s-pancreas-1 antigen (SPan-1) were retrospectively evaluated, and the positive number of these markers was scored as the pre-TI., Results: A high pre-TI (≥ 2) was significantly associated with a larger tumor and lymph node metastases, and the patients with a high pre-TI had worse prognostic outcomes in terms of both relapse-free survival (RFS) (P < 0.0001, log-rank) and overall survival (OS) (P < 0.0001, Λlog-rank) than the patients with a low pre-TI. The pre-TI was one of the independent factors of a poor prognosis for RFS (hazard ratio [HR], 2.36; P < 0.0001) and OS (HR, 2.27; P < 0.0001). In addition, even for the patients with normal adjusted CA19-9 values (n = 74, 40.4%), those with the high pre-TI had a significantly poorer prognosis than those with a low pre-TI (RFS: P = 0.002, log-rank; OS: P = 0.031, log-rank)., Conclusions: The pre-TI could be a potent predictive marker of prognostic outcomes for patients with resections for PDAC. Patients with a high pre-TI may need additional strategies to improve their prognosis.

Background: The clinical significance of programmed death 1 and its ligand (PD-L1) as therapeutic targets has been reported previously. This study aimed to investigate the clinical impact of PD-L1 expression in cancer and stroma cells in cholangiocarcinoma (CCA)., Methods: The study enrolled 177 consecutive CCA patients who underwent curative resection between 2005 and 2014. Expression of PD-L1 in CCA and stroma cells was assayed by immunohistochemistry, and their relationships with patient clinicopathologic characteristics and prognoses were evaluated. Tumor-infiltrating immune cells (CD66b + neutrophils [TANs] and CD163 + M2 macrophages [TAMs]) also were assayed by immunohistochemistry, and their relationship with PD-L1 expression in cancer and stroma cells was evaluated., Results: Among the 177 analyzed CCA cases, PD-L1 expression was identified in cancer cells in 54 cases (30.5%) and in stroma cells in 77 cases (43.5%). The patients with positive PD-L1 expression in cancer and stroma cells had worse overall survival rates than those negative for PD-L1 (cancer cells: hazard ratio [HR] 2.08; P = 0.0004; stroma cells: HR 1.84; P = 0.003). Moreover, the patients with PD-L1-positive cancer cells had higher rates of PD-L1 expression in stroma cells (P < 0.0001) and higher numbers of TANs (P = 0.0003) and TAMs (P = 0.004) than those with low PD-L1 expression. In the multivariate analysis, PD-L1 expression in both cancer and stroma cells (HR 2.20; P = 0.002) was an independent predictor of poor overall survival., Conclusions: The study showed PD-L1 expressed in both CCA and stromal cells and demonstrated that its expression may affect numbers of TANs and TAMs and play a pivotal role in CCA outcomes.

Background: The role of senescence of cancer-associated fibroblasts (CAFs) in the development of cancer is controversial. In this study, we investigated whether cellular senescence of CAFs, represented by CAV1 expression, affects tumor progression in pancreatic cancers (PC)., Methods: Because CAV1 plays a major role in cellular senescence, we used CAV1 expression to monitor cellular senescence. A total of 157 consecutive patients with PC who underwent curative resection were enrolled in the study. Patients were divided into two groups according to CAV1 expression in CAFs by immunohistochemistry. We investigated the relationship between the CAV1 expression in CAFs and the patients' clinicopathological characteristics, including survival. We also established ten CAFs cell lines using PC clinical samples and chose one of them to knock down CAV1 expression. Finally, we cultured a PC cell line (MIAPaCa-2) in CAF-conditioned medium (CM)., Results: Regarding patients' clinicopathological characteristics, the serum levels of carbohydrate antigen 19-9 and the rate of advanced tumor stage (pT2, 3, and 4) were significantly higher in the high-CAV1 group. The high-CAV1 group had significantly worse outcomes in both overall and disease-free survival (p < 0.01). Additionally, in co-culture assays using CAFs-CM and MIAPaCa-2 cells, we found that knockdown of CAV1 in CAFs negatively affected the invasion of PC cells., Conclusions: In PC, CAV1 expression in CAFs is associated with patients' poor prognosis and the downregulation of CAV1 in CAFs reduces the invasiveness of PC cells. Therefore, CAV1 of CAFs might be a new target for the treatment of PC.

Background: Less invasiveness is an important consideration for the treatment of hepatocellular carcinoma (HCC) especially in patients with severe cirrhosis., Methods: Between April 2000 and September 2016, 100 patients with liver damage B underwent multimodal radiofrequency ablation (RFA; n = 62) or laparoscopic hepatic resection (Lap-HR; n = 38) for primary HCC as defined by the Milan criteria. We compared the operative outcomes and patients' survival between the two groups., Results: The RFA group showed worse liver functions as indicated by indocyanine green retention rate (32.9 vs. 22.4%; p < 0.0001) and serum albumin value (3.3 vs. 3.6 g/dl; p = 0.0029). As expected, RFA was less invasive, as indicated by the differences in operation time (166 vs. 288 min.; p < 0.0001) and blood loss (8 vs. 377 g; p < 0.0001). There was no significant difference in the morbidity rate between the two groups; however, the duration of hospital stay of the RFA group was significantly shorter (7 vs. 11 days; p = 0.0002). There were no significant between-group differences regarding overall or disease-free survival., Conclusion: Multimodal RFA for HCC in patients with severe cirrhosis is associated with less invasiveness and shorter hospital stays, with no compromise in the patients' survival. In patients with severe cirrhosis, it may be time to consider changing the standard treatment for primary HCC within the Milan criteria to multimodal RFA.