Language：English   Publisher：Surgery Today  

Purposes: In pancreaticoduodenectomy for pancreatic ductal adenocarcinoma (PDAC), Prophylactic right-half dissection of the superior mesenteric artery (SMA) nerve plexus has been attempted in pancreaticoduodenectomy for pancreatic ductal adenocarcinoma. In this study, we evaluated the significance of prophylactic right-half dissection of the SMA nerve plexus by extending the observation period to 5 years. Methods: From April 2014 to June 2018, 74 patients with PDAC in the pancreatic head were randomly assigned to either the dissection group, in which the right half of the nerve plexus of the SMA was dissected (n = 37) or the preservation group, in which the nerve plexus of the SMA was completely preserved (n = 37). The 5-year relapse-free survival (RFS), overall survival (OS), and incidence of diarrhea were prospectively compared between groups. Results: The median RFS (20 vs. 16 months, P = 0.503) and OS (37.0 vs. 30.0 months, P = 0.582) did not differ significantly between the dissection and preservation groups. There was no significant difference in locoregional recurrence (27.0% vs. 37.8%, P = 0.320) or distant metastasis (64.9% vs. 83.0%, P = 0.451). Postoperative diarrhea occurred in 64.9% and 62.2% of the cases in the dissection and preservation groups, respectively (P = 0.809). Conclusion: Prophylactic right half dissection of the SMA nerve plexus did not improve the RFS or OS.

DOI： 10.1007/s00595-025-03062-6

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Language：English   Publisher：British Journal of Surgery  

DOI： 10.1093/bjs/znaf049

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Language：English   Publisher：Pancreas  

Objectives: Gemcitabine and nab-paclitaxel combination therapy (GnP) is a standard treatment for unresectable or recurrent pancreatic cancer. However, fatigue and malaise are frequent adverse effects. Recently, Kampo medicine containing ginsenoside has been reported to relieve cancer-related fatigue. Therefore, in this randomized trial, we used red ginseng powder (Koujin, TJ-3020), which contains ginsenoside, to evaluate its effect on unresectable or recurrent pancreatic cancer treatment. Materials and Methods: From December 2017 to December 2020, we enrolled 40 pancreatic cancer patients. The patients underwent 2 cycles of GnP for unresectable cancer or postoperative recurrence. The patients were randomized into group A (red ginseng powder administration) or group B (no red ginseng). In group A, 0.67 g of red ginseng powder was taken orally 3 times a day before each meal for 56 days of the planned chemotherapy period. The Cancer Fatigue Scale evaluated physical, mental, cognitive, and comprehensive fatigue over time. Results: The patients' backgrounds, including age, sex, pancreatic cancer status, and relative dose intensity of the GnP chemotherapy, did not differ between groups A and B. Cases with abnormal CA19-9 were frequently assigned to group A. None of the Cancer Fatigue Scale fatigue scores differed significantly between the groups. Mental fatigue score was significantly higher in patients aged ≥70 years (odds ratio: 4.57; P = 0.033), and recurrent pancreatic cancer status tended to influence all fatigue scores. However, no other critical factor significantly affected each score. Conclusions: In this phase II randomized trial, oral administration of red ginseng powder at 2.0 g per day did not reduce pancreatic cancer patients' fatigue or malaise induced by GnP combination chemotherapy.

DOI： 10.1097/MPA.0000000000002446

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Language：English   Publisher：Anticancer Research  

Background/Aim: Multimodal treatment is now the primary strategy for managing pancreatic cancer. Blood‑based protein markers are sometimes useless for evaluating the real‑time disease condition to determine treatment strategies. This study focused on detecting novel exosomal lipid biomarkers, as exosomes contain several biological mediators. Materials and Methods: Lipidomic analysis was conducted by liquid chromatography‑mass spectrometry (LC‑MS) using serum exosome‑derived lipid samples from four pancreatic ductal adenocarcinoma (PDAC) patients and four healthy controls. Some candidates were ascertained using multiple time‑point blood samples from four additional PDAC patients. Furthermore, we validated them using an additional twelve multimodal‑treated PDAC patient cohort. Results: Nontarget LC‑MS analysis revealed that lysophosphatidylcholine (LPC) expression levels were significantly decreased in PDAC patients compared to healthy controls. Multiple time‑point blood samples demonstrated that LPC (16:0) and LPC (18:1) consistently showed lower levels in relapsed cases than in non‑relapsed cases over time. In the validation cohort, a low LPC level before initial treatment was associated with histological lymphatic invasion (p=0.04) and was linked to progressive‑free survival (PFS) (p=0.04). Conclusion: PDAC patients with initially low LPC levels in the blood exosomes demonstrated an unfavorable PFS. Exosomal lipid markers may serve as potential indicators for disease monitoring in pancreatic cancer patients undergoing multimodal treatment.

DOI： 10.21873/anticanres.17520

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Language：English   Publisher：Anticancer Research  

Background/Aim: The severe malignancy of pancreatic ductal adenocarcinoma (PDAC) is mainly due to frequent local invasiveness and distant metastasis. As for local invasiveness, we previously reported that cancer-specific molecular alterations detected on resected PDAC specimen surfaces, so-called molecular surgical margin (MSM) positiveness, were significantly associated with postoperative locoregional recurrence and distant metastasis. However, due to anatomical limitations, achieving adequate surgical margins during pancreatic cancer resection is often challenging. Therefore, predicting local invasiveness based on the primary tumor’s gene profile is crucial to avoid positive MSM. Materials and Methods: Genome-wide miRNA expression profiles were examined and compared between MSM-positive and negative cases. Candidate miRNAs were evaluated in another validation cohort, and their clinicopathological characteristics were examined. Mimic or inhibitor constructs of the candidate miRNA were transfected to PDAC cell lines to evaluate the miRNA function in the pancreatic cancer cell lines and detect the downstream targets. Results: Among some candidates with highly expressed miRNAs in MSM-positive cases by miRNA expression array, recurrence-free survival (RFS) was significantly shorter in the miR-210-3p high expression group (p=0.015). High miR-210-3p was significantly associated with large tumor diameter (p=0.001), anterior invasion positive (p=0.010), and positive lymph node metastasis (p<0.001). miR-210-3p inhibition in PDAC cell lines resulted in decreased proliferation and invasiveness. The iron-sulfur cluster assembly enzyme (ISCU) gene was identified as a target of miR-210-3p. ISCU reduction was significantly observed in PDAC primary tumors with high levels of miR-210-3p, leading to mitochondrial dysfunction in miR-210-3p-overexpressing PDAC cell lines, as demonstrated by glycolysis stress tests. Conclusion: Highly expressed hypoxia-inducible miR-210-3p in primary PDAC tissues induces locally invasive characteristics through mitochondrial dysfunction by suppressing ISCU expression, which may result in poor postoperative RFS outcomes.

DOI： 10.21873/anticanres.17297

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