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BackgroundRobotic-assisted minimally invasive surgery is associated with worse oncologic outcomes for some but not other types of cancers. We conducted a propensity score-matched analysis to compare oncologic outcomes of robotic-assisted laparoscopic (RPD) vs. open pancreatoduodenectomy (OPD) for pancreatic ductal adenocarcinoma (PDAC).MethodsTreatment-naïve PDAC patients undergoing either RPD or OPD at our hospital between January 2013 and December 2017 were included. Propensity score matching was conducted at a ratio of 1:2. The primary outcome was disease-free survival (DFS) and overall survival (OS).ResultsA total of 672 cases were identified. The propensity score-matched cohort included 105 patients receiving RPD and 210 patients receiving OPD. The 2 groups did not differ in the number of retrieved lymph nodes [11 (7–16) vs. 11 (6–17), P = 0.622] and R0 resection rate (88.6% vs. 89.0%, P = 0.899). There was no statistically significant difference in median DFS (14 [95% CI 11–22] vs. 12 [95% CI 10–14] months (HR 0.94; 95% CI 0.87–1.50; log-rank P = 0.345) and median OS (27 [95% CI 22–35] vs. 20 [95% CI 18–24] months (HR 0.77; 95% CI 0.57–1.04; log-rank P = 0.087) between the two groups. Multivariate COX analysis showed that RPD was not an independent predictor of DFS (HR 0.90; 95% CI 0.68–1.19, P = 0.456) or OS (HR 0.77; 95% CI 0.57–1.05, P = 0.094).ConclusionComparable DFS and OS were observed between patients receiving RPD and OPD. This preliminary finding requires further confirmation with prospective randomized controlled trials.

BackgroundThis study aimed to compare the short-term outcomes of open and robotic-assisted distal pancreatectomy (ODP and RDP) for benign and low-grade malignant tumors.MethodsThe patients who underwent RDP and ODP for benign or low-grade malignant pancreatic tumors at our center were included. After PSM at a 1:1 ratio, the perioperative variations in the two cohorts were compared.ResultsAfter 1:1 PSM, 219 cases of RDP and ODP were recorded. The RDP cohort showed advantages in the operative duration [120 (90–150) min vs 175 (130–210) min, P < 0.001], estimated blood loss [50 (30–175) ml vs 200 (100–300) ml, P < 0.001], spleen preservation rate (63.5% vs 26.5%, P < 0.001), infection rate (4.6% vs 12.3%, P = 0.006), and gastrointestinal function recovery [3 (2–4) vs. 3 (3–5), P = 0.019]. There were no significant differences in postoperative pancreatic fistula, postoperative hemorrhage, and delayed gastric emptying. Multivariate analysis showed that RDP (HR 0.24; 95% CI 0.16–0.36, P < 0.001), age (HR 1.02; 95% CI 1.00–1.03, P = 0.033), tumor size (HR 1.28; 95% CI 1.17–1.40, P < 0.001), pathological inflammatory neoplasm type (HR 5.12; 95% CI 2.22–11.81, P < 0.001), and estimated blood loss (HR 1.003; 95% CI 1.001–1.004, P < 0.001) were independent predictors of spleen preservation; RDP (HR 0.27; 95% CI 0.17–0.43, P < 0.001), age (HR 1.02; 95% CI 1.00–1.03, P = 0.022), elevated CA 19–9 level (HR 2.55; 95% CI 1.02–6.39, P = 0.046), tumor size (HR 1.44; 95% CI 1.29–1.61, P < 0.001), pathological inflammatory neoplasm type (HR 4.48; 95% CI 1.69–11.85, P = 0.003), and estimated blood loss (HR 1.003; 95% CI 1.001–1.004, P < 0.001) were independent predictors of spleen preservation with the Kimura technique.ConclusionRDP has advantages in the operative time, blood loss, spleen preservation, infection rate, and gastrointestinal function recovery over ODP in treating benign and low-grade malignant pancreatic tumors. The robotic-assisted approach was an independent predictor of spleen preservation and use of the Kimura technique.

Background Immunotherapy has emerged as a potent clinical approach for cancer treatment, but only subsets of cancer patients can benefit from it. Targeting lactate metabolism (LM) in tumor cells as a method to potentiate anti-tumor immune responses represents a promising therapeutic strategy. Methods Public single-cell RNA-Seq (scRNA-seq) cohorts collected from patients who received immunotherapy were systematically gathered and scrutinized to delineate the association between LM and the immunotherapy response. A novel LM-related signature (LM.SIG) was formulated through an extensive examination of 40 pan-cancer scRNA-seq cohorts. Then, multiple machine learning (ML) algorithms were employed to validate the capacity of LM.SIG for immunotherapy response prediction and survival prognostication based on 8 immunotherapy transcriptomic cohorts and 30 The Cancer Genome Atlas (TCGA) pan-cancer datasets. Moreover, potential targets for immunotherapy were identified based on 17 CRISPR datasets and validated via in vivo and in vitro experiments. Results The assessment of LM was confirmed to possess a substantial relationship with immunotherapy resistance in 2 immunotherapy scRNA-seq cohorts. Based on large-scale pan-cancer data, there exists a notably adverse correlation between LM.SIG and anti-tumor immunity as well as imbalance infiltration of immune cells, whereas a positive association was observed between LM.SIG and pro-tumorigenic signaling. Utilizing this signature, the ML model predicted immunotherapy response and prognosis with an AUC of 0.73/0.80 in validation sets and 0.70/0.87 in testing sets respectively. Notably, LM.SIG exhibited superior predictive performance across various cancers compared to published signatures. Subsequently, CRISPR screening identified LDHA as a pan-cancer biomarker for estimating immunotherapy response and survival probability which was further validated using immunohistochemistry (IHC) and spatial transcriptomics (ST) datasets. Furthermore, experiments demonstrated that LDHA deficiency in pancreatic cancer elevated the CD8 + T cell antitumor immunity and improved macrophage antitumoral polarization, which in turn enhanced the efficacy of immunotherapy. Conclusions We unveiled the tight correlation between LM and resistance to immunotherapy and further established the pan-cancer LM.SIG, holds the potential to emerge as a competitive instrument for the selection of patients suitable for immunotherapy.

Epithelial-to-mesenchymal transition (EMT) is tightly associated with the invasion and metastasis of pancreatic cancer with rapid progression and poor prognosis. Notably, gene alternative splicing (AS) event plays a critical role in regulating the progression of pancreatic cancer. Therefore, this study aims to identify the EMT-related AS event in pancreatic cancer. The EMT-related gene sets, transcriptomes, and matched clinical data were obtained from the MSigDB, The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), and Gene Expression Omnibus (GEO) databases. Key gene AS events associated with liver metastasis were identified by prognostic analysis, gene set variation analysis (GSVA), and correlation analysis in pancreatic cancer. The cell line and organoid model was constructed to evaluate these key gene AS events in regulating pancreatic cancer . Furthermore, we established an EMT-related gene set consisting of 13 genes by prognostic analysis, the role of which was validated in two other databases. Finally, the human pancreatic cancer tissue and organoid model was used to evaluate the correlation between the enrichment of this gene set and liver metastasis. Prognostic analysis and correlation analysis revealed that eight AS events were closely associated with the prognosis of pancreatic cancer. Furthermore, the expression of TMC7 and CHECK1 AS events was increased in the metastatic lesions of the human tissue and organoid model. Additionally, the knockdown of exon 17 of TMC7 significantly inhibited the proliferation, invasion, and migration of pancreatic cancer cells in 2D and 3D cell experiments. Finally, the expression of exon 17 of TMC17 exhibited a significant correlation with the poor prognosis in pancreatic ductal adenocarcinoma (PDAC). The AS events of TMC7 and CHECK1 were associated with liver metastasis in pancreatic cancer. Moreover, exon 17 of TMC7 could be a potential therapeutic target in pancreatic cancer.

ObjectiveMiddle pancreatectomy (MP) is safe and feasible in patients with benign or low-grade malignant tumors located at the neck or proximal body of the pancreas. As a tissue-sparing operation, MP can preserve normal pancreatic function and reduce the risk of postoperative endocrine and exocrine insufficiency. However, the morbidity, especially the postoperative pancreatic fistula (POPF) rate, remains high. A robot-assisted surgical system may provide patients with less trauma; however, there are few reports on robot-assisted middle pancreatectomy (RMP). We describe the experience of RMP at our center to illustrate the learning curve (LC).MethodsFrom August 2010 to July 2017, 100 patients underwent RMP in the Pancreatic Disease Center of Shanghai Ruijin Hospital affiliated to Shanghai Jiaotong University School of Medicine. Patient characteristics, operative outcomes, and oncological outcomes were collected and analyzed. The CUSUM curve was analyzed according to operative time and estimated blood loss (EBL) and was used to describe the LC and identify the flexion points.ResultsAmong the 100 patients who underwent RMP in our hospital, the mean age was 47.5 ± 14.2 years, and 69 patients were female. From the CUSUM curve, we found two flexion points: cases 12 and 44. After 44 cases, the rate of improvement was much faster. We separated the patients into two groups based on the LC (cases 1–44 and cases 45–100). There were significant improvements in operative time (173.1 ± 44.7 min vs. 137.3 ± 30.1 min, p < 0.001) and EBL (103.4 ± 90.0 ml vs. 69.3 ± 53.9 ml, p = 0.021). The overall POPF rate was 32% (32/100), while the incidence rate of biochemical leakage was 14% (14/100). However, there was no significant difference in the risk of POPF or other complications between the two groups. The postoperative length of stay (LOS) was also not different. The 90-day mortality rate was 1%. From our long-term follow-up, pancreatic function was preserved in most patients, with only three cases of endocrine insufficiency and two cases of exocrine insufficiency.ConclusionRMP was helpful and a good choice for the selected patients. PF was the main complication and has not been improved until now. There were two flexion points in the LC at cases 12 and 44. More cases are needed to gain more experience. A larger sample size and prospective studies are needed to verify the advantage of RMP.

Background Patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) face a notable risk of suicide. However, comprehensive population‐based studies on suicide risk in PDAC patients have been lacking. This study seeks to explore the suicide risk in PDAC patients and identify the specific risk factors associated with suicide‐related mortality. Methods A cohort of 101,382 PDAC patients was extracted from the Surveillance, Epidemiology, and End Results database, spanning from January 1, 2000, to December 31, 2017. The study employed the standardized mortality ratio (SMR) to assess the relative risk of suicide in PDAC patients compared to the general US population. The Nelson–Aalen estimator and the Fine and Grey method were utilized to pinpoint the risk factors linked to suicide‐specific mortality. Results PDAC patients exhibited a 3.51‐fold higher risk of suicide compared to the general US population. This risk demonstrated an upward trend over the years. Notably, individuals aged 70–74 years faced a significantly elevated risk of suicide (SMR = 5.14, 95% CI: 3.10–8.03). Furthermore, there were distinct peaks in suicide risk at 1–4‐ and 25–28‐month post‐diagnoses (SMR = 15.04 and 2.72, respectively). Factors, such as gender, chemotherapy status, and marital status, emerged as significant independent predictors of suicide‐specific mortality in PDAC patients. Conclusions This study highlights a heightened suicide risk among PDAC patients in comparison to the general US population. It underscores the crucial need for continuous monitoring of the psychological well‐being of all PDAC patients. Additionally, considering the elevated risk, the application of antidepressant therapy could be beneficial for those identified as having a higher risk of suicide. Graphical : PDAC patients exhibited a 3.51‐fold higher risk of suicide compared to the general US population. This risk demonstrated an upward trend over the years. Notably, individuals aged 70–74 years faced a significantly elevated risk of suicide (SMR = 5.14, 95% CI: 3.10–8.03). Furthermore, there were distinct peaks in suicide risk at 1–4‐ and 25–28‐month post‐diagnoses (SMR = 15.04 and 2.72, respectively). Factors, such as gender, chemotherapy status, and marital status, emerged as significant independent predictors of suicide‐specific mortality in PDAC patients.

Background Primary tumor resection (PTR) as a treatment option for patients with stage IV pancreatic cancer (PC) is controversial. Patients and methods Stage IV PC patients, with treatment data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER), were screened. The main outcomes were overall survival (OS) and cancer‐specific survival (CSS). Results We enrolled 15,836 stage IV PC patients in this study. Propensity score‐matched analyses revealed improved OS and CSS of patients receiving chemotherapy plus PTR versus chemotherapy (median survival time [MSTOS]: 13 vs. 9 months, p = 0.024; MSTCSS: 14 vs. 10 months, p = 0.035), and chemoradiotherapy plus PTR versus chemoradiotherapy (MSTOS: 14 vs. 7 months, p = 0.044; MSTCSS: 14 vs. 7 months, p = 0.066). Multivariate adjusted analyses further confirmed these results. Stratified with different metastatic modalities, multivariate analyses suggested that PTR significantly improved the OS and CSS among patients with ≤1 metastatic organ, and that patients with brain metastasis might not benefit from chemotherapy treatment. Conclusion PTR improves the OS and CSS of stage IV PC patients on the basis of chemotherapy or chemoradiotherapy, provided that the metastases involve ≤1 organ. Chemotherapy, however, should be carefully considered in patients with metastases involving the brain. Primary site resection should be recommended for stage IV pancreatic cancer patients, provided that synchronous chemotherapy/chemoradiotherapy was administrated. Chemotherapy, however, may not bring survival benefits for those with brain metastases.

Pancreatic cancer is an extremely lethal digestive cancer with late diagnosis and poor prognosis. miR-934 has been reported to serve as an oncogene in multiple cancers, such as ovarian cancer and bladder cancer. However, its role in pancreatic cancer remains undiscovered. The expression data of miR-934 were obtained from the Gene Expression Omnibus database and from our own patient samples. The clinicopathological data and corresponding follow-up data were retrieved from The Cancer Genome Atlas database. CCK8 and colony formation assays were conducted to measure cell proliferation capacity in vitro. Wound healing and transwell assays were performed to detect the migration ability of pancreatic cancer cell. We found that miR-934 was significantly upregulated in pancreatic tumor samples and cell lines. The expression of miR-934 was related to pathological stages. Upregulated miR-934 was associated with poor prognosis in patients with pancreatic cancer. Mir-934 inhibition reduced, while overexpression promoted, cell proliferation and migration. Mechanically, we found  miR-934 could directly bind to 3'-UTR of PROX1 leading to mRNA derogation. Furthermore, increased cell proliferation and migration caused by miR-934 overexpression could be reversed by forced PROX1 expression. miR-934 is an oncogene in pancreatic cancer and could serve as a prognosis indicator for patients with pancreatic cancer, suggesting that miR-934 is a promising therapeutic target for pancreatic cancer.

Pre-mRNA processing factor 40 homolog A (PRPF40A) is an important protein involved in pre-mRNA splicing and is expressed in a variety of cell types. However, the function of PRPF40A in pancreatic cancer remains unclear. Therefore, our study is to investigate the role of PRPF40A in the pathogenesis of pancreatic cancer. We extracted expression data and clinical information of PRPF40A from different online databases, including the Cancer Genome Atlas (TCGA), Oncomine and the Gene Expression Omnibus (GEO). Subsequently, samples were collected from patients to validate gene expression using qPCR, Western blotting and immunohistochemical (IHC) analyses. Receiver operating characteristic (ROC) and Kaplan-Meier curve were used to evaluate the diagnostic and prognostic potential. Colony formation assays and CCK-8 assays were performed to measure the proliferative capacity of pancreatic cancer. Finally, gene ontology (GO) and pathway enrichment analyses of co-expressed genes of PRPF40A were conducted using the Database for Annotation, Visualization and Integrated Discovery (DAVID). We found that PRPF40A was upregulated based on data from both the online databases and our samples. PRPF40A possessed a significant diagnostic value, and its overexpression was associated with poor prognosis. PRPF40A knockdown inhibited cell proliferation in pancreatic cancer. GO and pathway analysis showed that the co-expressed genes were mainly involved in viral processing, mRNA splicing and the AMPK signaling pathway. The results suggest that PRPF40A is an oncogene and can serve as a diagnostic and prognostic biomarker for pancreatic cancer. However, the underlying mechanisms remain to be elucidated.

目的 探索高频不可逆电穿孔 (H-FIRE) 消融猪胰腺组织的效果。 方法 采用开腹手术，借助针式电极对12只猪释放电脉冲，按照场强数值小、中、大设置三组参数 (1 000 V/cm、1 500 V/cm、2 500 V/cm) 进行消融。通过比较各组术后恢复情况、消融面积、组织病理学表现等数据验证H-FIRE消融猪胰腺组织的安全性、有效性。计量资料两组间比较使用配对t检验。 结果 所有实验猪均存活，且获得明确的消融效果，各组组织病理学均提示，消融有效彻底，消融区与正常组织区分界明显，小场强组、中场强组、大场强组平均消融面积分别为 (30.96±3.73) mm2、 (51.93±25.26) mm2、 (108.90±55.23) mm2，大、中场强组消融面积均显著大于小场强组 (P值均<0.05) ，中场强组与大场强组消融面积差异无统计学意义 (P>0.05) 。 结论 在特定的消融参数下，对猪胰腺进行H-FIRE消融安全、有效。