Explore the vast range of titles available.

BackgroundThe 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).MethodsThe 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.ResultsAmong 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.ConclusionsThe 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.

AimLaparoscopic 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.MethodsFrom 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.ResultsAntecolic 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.ConclusionD-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.

Immunotherapy using anti‐PD‐1/PD‐L1 antibodies for several types of cancer has received considerable attention in recent decades. However, the molecular mechanism underlying PD‐L1 expression in pancreatic ductal adenocarcinoma (PDAC) cells has not been clearly elucidated. We investigated the clinical significance and regulatory mechanism of PD‐L1 expression in PDAC cells. Among the various cytokines tested, tumor necrosis factor (TNF)‐α upregulated PD‐L1 expression in PDAC cells through NF‐κB signaling. The induction of PD‐L1 expression was also caused by co‐culture with activated macrophages, and the upregulation was inhibited by neutralization with anti‐TNF‐α antibody after co‐culture with activated macrophages. PD‐L1 expression in PDAC cells was positively correlated with macrophage infiltration in tumor stroma of human PDAC tissues. In addition, survival analysis revealed that high PD‐L1 expression was significantly associated with poor prognosis in 235 PDAC patients and especially in patients harboring high CD8‐positive T‐cell infiltration. These findings indicate that tumor‐infiltrating macrophage‐derived TNF‐α could be a potential therapeutic target for PDAC. Survival analysis revealed that PD‐L1 expression was significantly associated with poor prognosis in PDAC patients and especially in patients harboring high CD8‐positive T‐cell infiltration. The induction of PD‐L1 expression was caused by co‐culture with activated macrophages, and the upregulation was inhibited by neutralization with anti‐TNF‐α antibody after co‐culture with activated macrophages.

BackgroundThe 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.MethodsFor 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.ResultsA 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).ConclusionsThe 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 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.

Chronic inflammation has a crucial role in cancer development and the progression of various tumors, including pancreatic ductal adenocarcinoma (PDAC). The arachidonate cascade is a major inflammatory pathway that produces several metabolites, such as prostaglandin E2. The enzyme 15‐hydroxyprostaglandin dehydrogenase (15‐PGDH) degrades prostaglandin and is frequently decreased in several types of cancer; however, the molecular mechanisms of 15‐PGDH suppression are unclear. The current study was carried out to elucidate the molecular mechanisms and clinical significance of 15‐PGDH suppression in PDAC. Here, we showed that interleukin‐1β (IL‐1β), a pro‐inflammatory cytokine, downregulates 15‐PGDH expression in PDAC cells, and that IL‐1β expression was inversely correlated with 15‐PGDH levels in frozen PDAC tissues. We also found that activated macrophages produced IL‐1β and reduced 15‐PGDH expression in PDAC cells. Furthermore, the number of CD163‐positive tumor‐associated macrophages was shown to be inversely correlated with 15‐PGDH levels in PDAC cells by immunohistochemical staining of 107 PDAC samples. Finally, we found that low 15‐PGDH expression was significantly associated with advanced tumors, presence of lymph node metastasis and nerve invasion, and poor prognosis in PDAC patients. Our results indicate that IL‐1β derived from TAMs suppresses 15‐PGDH expression in PDAC cells, resulting in poor prognosis of PDAC patients. IL‐1β derived from activated macrophages down‐regulates 15‐PGDH expression in PDAC cells. Down‐regulation of 15‐PGDH promotes PDAC cell growth and leads to poor prognosis in PDAC patients.

Patients' prognoses have been predicted by the preoperative inflammation-based score, but predicting a patient's risk for operative load remains challenging. This study investigates the usefulness of the postoperative C-reactive protein/albumin (CRP/Alb) ratio in patients with pancreatic ductal adenocarcinoma (PDAC). This study retrospectively assessed 142 patients who underwent pancreatic resection for PDAC between 2004 and 2014. The time at which perioperative CRP/Alb ratio most influences the prognosis was identified, and the correlations among the perioperative CRP/Alb ratio, clinicopathological factors, and patient outcomes were investigated. Among the perioperative CRP/Alb ratios, only a high CRP/Alb ratio at postoperative day 14 (POD14) was significantly associated with shorter overall survival (OS) and relapse-free survival (RFS). High CRP/Alb ratio at POD 14 was related to high BMI, large amount of intraoperative bleeding, and the presence of complications. Finally, high CRP/Alb at POD14 was an independent prognostic factor of poor OS and RFS. The CRP/Alb ratio at POD14 is a useful predictive marker of surgical invasion, biological reaction, and prognosis in PDAC patients.

BackgroundLess invasiveness is an important consideration for the treatment of hepatocellular carcinoma (HCC) especially in patients with severe cirrhosis.MethodsBetween 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.ResultsThe 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.ConclusionMultimodal 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.

PurposesThis study aimed to clarify the impact of postoperative nonalcoholic fatty liver disease (NAFLD) on the clinical course of patients with pancreatic ductal adenocarcinoma (PDAC).MethodsOne hundred and eight patients with pancreatic cancer undergoing pancreaticoduodenectomy (PD) with curative intent in between 2005 and 2016 were enrolled in this study. Post-PD NAFLD was assessed by computed tomography (CT), which was routinely performed at 3 months, 6 months, and 1 year after surgery. The clinical impact of post-PD NAFLD was examined from an oncological perspective.ResultsThere were 50 (46.2%) post-PD NAFLD patients. The NAFLD group showed significantly lower CT values at 3 months, 6 months, and 1 year after surgery than those without NAFLD. Patients with NAFLD showed significant body weight loss and a decrease in serum albumin level after surgery compared with those without NAFLD. Consequently, the 70% completion rate of adjuvant chemotherapy with gemcitabine, but not S1, was significantly lower in the NAFLD group than in the non-NAFLD group. The 5-year overall survival and disease-free survival rates were comparable between the two groups.ConclusionPost-PD NAFLD was associated with malnutrition in patients with PDAC, reducing their tolerance to gemcitabine-based adjuvant chemotherapy. Post-PD NAFLD needs to be emphasized and requires special nutritional intervention in patients with PDAC.

PurposesThe indication of endoscopic (laparoscopic and thoracoscopic) hepatic resection (HR) has been expanded in the past decade because of its low invasiveness. However, the indications of endoscopic HR and radiofrequency ablation (RFA) have not yet been determined.MethodsAmong the 906 patients hospitalized for the initial treatment of hepatocellular carcinoma (HCC) between 2000 and 2017, 77 underwent endoscopic partial HR (E-pHR), and 94 underwent endoscopic RFA (E-RFA). We compared the short- and long-term outcomes between the E-pHR and E-RFA groups.ResultsThe patients in the E-RFA group were characterized primarily by an impaired liver function. Among the patients with liver damage B or C, the overall survival (OS) in the E-pHR group was significantly worse than in the E-RFA group (3-year OS: 36% vs. 82%, p = 0.003).ConclusionE-RFA may be recommended for the initial treatment of HCC in patients with a severely impaired liver function. However, E-pHR should be avoided as the initial treatment of HCC in such patients.