Pancreas最新文献

Objectives: This study assessed the anticancer potential of genetically modified exosomes engineered to express CD133-binding peptides on their surface and carry PD-L1 siRNA for the treatment of murine model of metastatic pancreatic cancer.

Methods: CD133-targeting exosomes (tEx) were generated by harvesting conditioned media from adipose-derived stem cells (ASCs) that had undergone transformation using pDisplay vectors encoding CD133-binding peptide sequences. Subsequently, siPD-L1-loaded CD133-targeting Exosomes, referred to as tEx(s), were created by incorporating PD-L1 siRNA into the tEx using Exofect kit.

Results: tEx(s) demonstrated superior targetability compared to other materials, including Ex, Ex(p), and tEx. This was substantiated by higher Total Radiant Efficiency (TRE) observed in metastatic liver and pancreatic tissues following intravenous administration of tEx(s) ( P < 0.05). Furthermore, the intravenous delivery of tEx(s) resulted in the most pronounced upregulation of pro-apoptotic markers (BIM and c-caspase 3) and the least downregulation of the anti-apoptotic markers (Mcl-1 and Bcl-xL) which has been demonstrated in various methods, including RT-PCR, Western blot analysis, and immunohistochemistry in the metastatic lesions in the livers ( P < 0.05).

Conclusions: PD-L1 siRNA-loaded CD133-targeting exosomes demonstrated remarkable anticancer efficacy, characterized by specific binding to CD133-positive pancreatic cancer cells and suppression of PD-L1 expression within these cells.

Background: Distinguishing serous cystadenoma, a benign pancreatic cyst, from potentially malignant mucinous pancreatic cystic lesions carries significant clinical and prognostic implications; and while endoscopic ultrasound-guided fine needle aspiration is the standard diagnostic tool, its low diagnostic yield often results in additional workup.

Objective: This study evaluates diagnostic yield of fine needle biopsy (FNB) on lesions suggestive of serous cystadenoma on endoscopic ultrasound.

Methods: Patients with microcystic EUS appearance were identified through retrospective chart review in two institutions. Prior cross sectional imaging diagnosis was also obtained. All microcystic lesions with classic "honeycomb" appearance for serous cystadenoma on EUS were targeted for FNB and their pathology evaluated. Patients were identified through database search from 2015 to 2022 and procedure information was obtained through a retrospective chart review from two large academic centers.

Results: Thirty-one patients with suspected serous cystadenoma who underwent EUS-FNB were included. EUS FNB was successful in obtaining diagnosis in 96.8% of patients. Serous cystadenoma was diagnosed via EUS FNB in 27 of 31 patients (87.1%). Of the remaining four patients, there was one invasive pancreatic ductal adenocarcinoma, one pancreatic neuroendocrine tumor, one intraductal papillary mucinous neoplasm, and one nondiagnostic sample.

Conclusion: EUS-FNB sampling for histopathology is a safe and accurate diagnostic tool for pancreatic serous cystadenoma. When microcytic lesions are found on endoscopic ultrasound, our study results suggest that fine needle biopsy for histopathology should be considered as the initial diagnostic evaluation tool given the demonstrated improved diagnostic yield for serous cystadenoma.

Background: Liver recurrence after resection is one of the most common types of recurrence and is a risk factor for poor prognosis. The aim of this study was to identify risk factors for initial liver recurrence.

Methods: Total of 109 patients with resectable pancreatic ductal adenocarcinoma who underwent resection between 2015 and 2022 were included. The influence of clinicopathologic variables on liver recurrence was analyzed to create a novel scoring system to predict liver recurrence.

Results: The liver recurrence rate was 24%, with 17% recurrence within one year. Patients with liver recurrence had an extremely poor prognosis within 1 year [MST 12.4 (95% CI 5.7-19.1)]. In multivariate analysis, R-PV, large tumor diameter ≥ 45 mm and venous invasion were independent risk factors for early liver recurrence. When each of these risk factors was scored as 1 point, the 1-year liver recurrence rates by score were 0 (0%), 1 (9%), 2 (30%), and 3 (84%).

Conclusion: The risk factors for postoperative early liver recurrence were R-PV, a tumor diameter ≥ 45 mm and pathological venous invasion. Surgery for pancreatic cancer with these factors may require special treatment, such as hepatic arterial injection.

Objectives: Acute pancreatitis (AP) can lead to severe complications and high mortality. Previous studies suggest that epidural analgesia (EA) may reduce AP severity and improve outcomes. This systematic review and meta-analysis aimed to evaluate the efficacy of EA on in-hospital outcomes in AP patients.

Method: Electronic databases (PubMed, Medline-Ovid, Scopus, CINAHL, Web of Science) were systematically searched until mid-May 2024 for RCTs comparing EA with other pain management strategies in AP patients. Variables were pooled using weighted mean difference (WMD) or risk ratio (RR) with 95% confidence intervals (CIs). Data analysis employed a random-effects model and the Mantel-Haenszel method. Study heterogeneity was assessed using the I2 statistic.

Results: Five RCTs with 260 participants were included. Meta-analysis showed no significant differences in in-hospital mortality (RR = 0.69, 95% CI [0.29, 1.65], p = 0.40), mechanical ventilation (RR = 0.82, 95% CI [0.61, 1.10], p = 0.19), sepsis events (RR = 0.88, 95% CI [0.42, 1.86], p = 0.74), hospital/ICU stay (WMD = 0.49 days, 95% CI [-1.13, 2.10], p = 0.55), and pain score (WMD = 1.49, 95% CI [-0.42, 3.40], p = 0.13). However, opioid requirements were significantly lower, as reported by one study with morphine milligram equivalent of 15 mg/day compared to 52 mg/day in the control group (p = 0.001). Heterogeneity was low to moderate for most outcomes but high for pain score (I2 = 92%). The overall certainty of evidence was very low due to the small number of studies, risk of bias, and limited sample size.

Conclusions: EA did not significantly improve in-hospital outcomes in AP patients. However, findings indicated reduced opioid consumption in the EA group, suggesting potential benefits in pain management. Further high-quality, large-scale randomized trials are needed to understand the potential benefits of EA in this population.

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.

Methods: From December 2017 to December 2020, we enrolled 40 pancreatic cancer patients. The patients underwent two 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 three 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 the physical, cognitive, and comprehensive fatigue scores.

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.

Objectives: Activation of type M2 macrophages has been implicated in the pathogenesis of chronic pancreatitis (CP). In a clinical pilot study, we investigated blood-based markers of macrophage activation at different stages of CP.

Methods: We performed a cross-sectional analysis of prospectively collected plasma samples from healthy controls and patients with suspected or definitive CP according to the M-ANNHEIM criteria. Plasma concentrations of soluble CD163 (sCD163), soluble CD206 (sCD206), and monocyte chemoattractant protein-1 (MCP-1) were analyzed using enzyme-linked immunosorbent assays. Group and pairwise comparisons of analytes were performed using regression models and area under the receiver operating curves (AUC-ROC).

Results: In total, 73 subjects with CP (28 suspected CP and 45 definitive CP) and 40 controls were included. Compared to controls, the median plasma concentrations of sCD163 (p = 0.019) and sCD206 (p = 0.033) were elevated in patients with definitive CP. sCD206 was also elevated in patients with definitive CP (p = 0.042). ROC analysis revealed that the optimal sCD163 cutpoint to distinguish definitive CP from controls was 1.84 mg/ml (AUC-ROC 0.65; 95 % confidence interval [CI], 0.54-0.77). The optimal sCD206 cutpoint to distinguish definitive CP from controls was 0.24 mg/ml (AUC-ROC 0.66; 95 % CI 0.54-0.78). The analytes did not significantly discriminate patients with suspected CP from controls. MCP-1 concentrations showed no differences across subgroups.

Conclusion: Our study demonstrates that subjects with definitive CP, sampled during a clinically quiescent phase, exhibited increased levels of sCD163 and sCD206. This indicates the presence of activated M2 macrophages in patients with CP at advanced, but not early, clinical stages.

Objectives: To evaluate patient preferences for decision-making role in the management of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas and to identify individual characteristics associated with those preferences.

Background: Management of IPMNs is rooted in uncertainty with current guidelines failing to incorporate patients' preferences and values.

Methods: A representative sample of participants aged 40-70 were recruited to evaluate a clinical vignette where they were given the option to undergo surveillance or surgical resection of their IPMN. Their preferred role in the decision-making process for the vignette was evaluated using the Control Preference Scale. The relationship between control preference and variables including cancer anxiety, health literacy, and education level was analyzed.

Results: Of the 520 participants in the study, most preferred an active role (65%), followed by shared (29%), and passive roles (6%) in the decision-making process. Lower health literacy was significantly associated with a more passive control preference (p = 0.003). Non-active preference was significantly associated with Latino race compared to White race (odds ratio = 0.52, p = 0.009) in multivariate analysis. We found no significant association between control preference and education level or cancer anxiety.

Conclusions: Most patients preferred an active role in IPMN treatment decisions. Lower health literacy and Latino race were associated with a preference for non-active decision roles. Clinicians should strive to align patient involvement in IPMN treatment decisions with their patient's preferred role.