Total laparoscopic partial hepatectomy versus open partial hepatectomy for primary left-sided hepatolithiasis: study protocol for a randomized controlled trial.

BACKGROUND: The advantages of laparoscopic left-sided hepatectomy (LLH) for treating hepatolithiasis in terms of the time to postoperative length of hospital stay (LOS), morbidity, long-term abdominal wall hernias, hospital costs, residual stone rate, and recurrence of calculus have not been confirmed by a randomized controlled trial. The aim of this trial is to compare the safety and effectiveness of LLH with open left-sided hepatectomy (OLH) for the treatment of hepatolithiasis. METHODS: Patients with hepatolithiasis eligible for left-sided hepatectomy will be recruited. The experimental design will produce two randomized arms (laparoscopic and open hepatectomy) at a 1:1 ratio and a prospective registry. All patients will undergo surgery in the setting of an enhanced recovery after surgery (ERAS) programme. The prospective registry will be based on patients who cannot be randomized because of the explicit treatment preference of the patient or surgeon or because of ineligibility (not meeting the inclusion and exclusion criteria) for randomization in this trial. The primary outcome is the LOS. The secondary outcomes are percentage readmission, morbidity, mortality, hospital costs, long-term incidence of incisional hernias, residual stone rate, and recurrence of calculus. It will be assumed that, in patients undergoing LLH, the length of hospital stay will be reduced by 1 day. A sample size of 86 patients in each randomization arm has been calculated as sufficient to detect a 1-day reduction in LOS [90% power and α = 0.05 (two-tailed)]. The trial is a randomized controlled trial that will provide evidence for the merits of laparoscopic surgery in patients undergoing liver resection within an ERAS programme. CONCLUSIONS: Although the outcomes of LLH have been proven to be comparable to those of OLH in retrospective studies, the use of LLH remains restricted, partly due to the lack of short- and long-term informative RCTs pertaining to patients with hepatolithiasis in ERAS programmes. To evaluate the surgical and long-term outcomes of LLH, we will perform a prospective RCT to compare LLH with OLH for hepatolithiasis within an ERAS programme. TRIAL REGISTRATION: ClinicalTrials.gov NCT03958825. Registered on 21 May 2019.

Single-cell sequencing reveals heterogeneity between pancreatic adenosquamous carcinoma and pancreatic ductal adenocarcinoma with prognostic value.

Pancreatic adenosquamous carcinoma (ASPC) is a rare subtype of pancreatic cancer with lethal malignancy, and few studies have focused on the heterogeneity of ASPC. Here, we performed a single-cell sequencing procedure on pancreatic tumor tissue from an ASPC patient and a patient with high-grade intraductal papillary mucinous neoplasm (IPMN). Through the combined analysis of single-cell sequencing data from five pancreatic ductal adenocarcinoma (PDAC) patients, one IPMN patient, and one ASPC patient in a public database, we identified 11 main types of cells, including macrophages, B cells, cancer stem cells, ductal cells, fibroblasts, endo/stellate cells, neutrophils, acinar cells, T cells, natural killer (NK) cells, dendritic cells, and mast cells. Then, the different characteristics and differentiation paths of the immune microenvironment among IPMN, ASPC, and PDAC in macrophages, T cells, and cancer-associated fibroblasts (CAFs) were identified through multiple bioinformatics analyses. Two novel special cancer-associated fibroblasts were identified as nCAFs and imCAFs. Then, cancer cells in duct cells were identified using the infercnv software. Two ASPC-specific subgroups of cancer cells with squamous cell features were identified. Finally, the identified specific CAFs and cancer cells were mapped to TCGA-PAAD cohort through the cibersoftx software. All of these identified subgroups were calculated to have a significant prognostic value in pancreatic cancer patients. These findings will promote the clinical application of single-cell sequencing data of pancreatic cancer and deepen our understanding of ASPC.

The clinical impact of endoscopic ultrasound-guided fine-needle aspiration on the patients with low-risk pancreatic cystic lesions.

Background and aims: Endoscopic ultrasound (EUS) is playing a more and more important role in the management of pancreatic cystic lesion (PCLs). The aim of our study was to evaluate the clinical impact of EUS and EUS guided fine needle aspiration (FNA) on patients with low-risk PCLs. Materials and methods: Low-risk PCL patients who underwent EUS-FNA in 2 edoscopic centers were retrospectively collected and analyzed. The clinical impact of EUS-FNA on these patients was analyzed and the predictors for significance EUS-FNA (defined by diagnosis and treatment method change, new high-risk feature identified after imaging scans) were analyzed by logistic regression analyses. Results: From July 2004 to February 2017, 186 patients with low-risk PCLs were included. The study cohort had a mean age of 52.4 ± 15.9 years (range: 19-86 years) with 89 (47.8%) male patients included. The clinical significance of EUS-FNAs was observed in 74 patients (39.8%). The presumed diagnoses of PCLs by imaging were changed in 51 (51/74, 68.9%) patients. Nineteen (19/74, 25.7%) new high-risk features were identified by EUS-FNA, and four patients (4/74, 5.4%) underwent surgery due to suspicious or malignant cytology. Based on multivariate analysis, large cyst size [odds ratio (OR): 1.12, 95% confidence interval (CI): 1.02-1.19, P = 0.033], young age (OR: 0.94, 95% CI: 0.91-0.99, P = 0.041) and BMI over 25 (OR: 3.15, 95% CI: 1.29-7.86, P = 0.013) were independent predictors of clinical significance for EUS-FNA. The optimal age and cyst size to predict significance EUS-FNA was 46.0 years and 2.3cm. Conclusions: On the basis of a 2-center retrospective study, EUS-FNA was clinically significant in about 40% of low-risk PCLs, especially in young, large cyst size, and overweight patients.

NOL12 as an Oncogenic Biomarker Promotes Hepatocellular Carcinoma Growth and Metastasis.

Hepatocellular carcinoma (HCC) is a common malignancy with a poor prognosis worldwide. However, the pathogenesis of HCC remains poorly understood. In this study, we found that NOL12 was significantly overexpressed in independent HCC datasets from TCGA database. We confirmed that the expression level of NOL12 was upregulated in human HCC tissues and cell lines by RT-qPCR. High expression of NOL12 is associated with worse reduced overall survival (OS), high pathological grade, node metastasis, and advanced clinical stage in patients with HCC. Moreover, knockdown of NOL12 dramatically inhibits the proliferation and metastasis of HCC cells in vitro and in vivo. CIBERSORTx analysis revealed that twelve types of tumor-infiltrating immune cells (TICs) are correlated with NOL12 expression. The risk signature based on 8 NOL12-related genes is an independent prognostic factor for patients with HCC. The OS rate of patients in the low-risk score group was better than that in the high-risk score group. In addition, the total tumor mutation burden (TMB) in the high-risk score group increased significantly, and the risk scores could be used as an alternative indicator of immune checkpoint inhibitor (ICI) response. In conclusion, our findings indicated that NOL12 might be involved in the progression of HCC and can be used as a potential therapeutic target. Moreover, the NOL12-related risk signature may have predictive relevance with regard to ICI therapy.

Impact of parenchyma-preserving surgical methods on treating patients with solid pseudopapillary neoplasms: A retrospective study with a large sample size.

BACKGROUND: Solid pseudopapillary neoplasm (SPN) of the pancreas is a rare neoplasm that mainly affects young women. AIM: To evaluate the impact of parenchyma-preserving surgical methods (PPMs, including enucleation and central pancreatectomy) in the treatment of SPN patients. METHODS: From 2013 to 2019, patients who underwent pancreatectomy for SPNs were retrospectively reviewed. The baseline characteristics, intraoperative index, pathological outcomes, short-term complications and long-term follow-up data were compared between the PPM group and the conventional method (CM) group. RESULTS: In total, 166 patients were included in this study. Of them, 33 patients (19.9%) underwent PPM. Most of the tumors (104/166, 62.7%) were found accidentally. Comparing the parameters between groups, the hospital stay d (12.35 vs 13.5 d, P = 0.49), total expense (44213 vs 54084 yuan, P = 0.21), operation duration (135 vs 120 min, P = 0.71), and intraoperative bleeding volume (200 vs 100 mL, P = 0.49) did not differ between groups. Regarding pathological outcomes, tumor size (45 vs 32 mm, P = 0.07), Ki67 index (P = 0.53), peripheral tissue invasion (11.3% vs 9.1%, P = 0.43) and positive margin status (7.5% vs 6%, P = 0.28) also did not differ between groups. Moreover, PPM did not increase the risk of severe postoperative pancreatic fistula (3.8% vs 3.0%, P = 0.85) or tumor recurrence (3.0% vs 6.0%, P = 0.39). However, the number of patients who had exocrine insufficiency during follow-up was significantly lower in the PPM group (21.8% vs 3%, P = 0.024). CM was identified as an independent risk factor for pancreatic exocrine insufficiency (odds ratio = 8.195, 95% confident interval: 1.067-62.93). CONCLUSION: PPM for SPN appears to be feasible and safe for preserving the exocrine function of the pancreas.

The RNA-Binding Protein NELFE Promotes Gastric Cancer Growth and Metastasis Through E2F2.

Worldwide, the incidence rate of gastric cancer ranks fifth, and the mortality rate of gastric cancer ranks third among all malignant tumors. However, the pathogenesis of gastric cancer remains poorly understood. In this study, we demonstrated that the expression level of NELFE is higher in human gastric cancer tissues than in adjacent nontumor tissues. A high level of NELFE is associated with worse postoperative overall survival (OS) and relapse-free survival (RFS) rates in patients with gastric cancer. Moreover, the expression of NELFE is correlated with high tumor grade and lymph node metastasis in gastric cancer patients. Knockdown of NELFE dramatically inhibits the cell proliferation and metastasis of gastric cancer xenografts in vivo. Furthermore, we found that NELFE binding to the 3'UTR of E2F2 affects the mRNA stability of E2F2 to regulate the expression level of E2F2. In gastric cancer, E2F2 also acts as an oncogene to inhibit the proliferation and migration of gastric cancer cells by knocking down the expression level of E2F2. However, overexpressing E2F2 in cells with NELFE knockdown significantly reverses the inhibition of cell proliferation and migration induced by NELFE knockdown. Therefore, NELFE at least partially functions as an oncogene through E2F2. Moreover, CIBERSORTx analysis of the proportion of tumor-infiltrating immune cells (TICs) revealed that immune cells are correlated with NELFE and E2F2 expression, suggesting that NELFE and E2F2 might be responsible for the preservation of the immunodominant status for gastric cancer. In conclusion, NELFE acts as an oncogene in gastric cancer and can be used as a potential therapeutic target.

Dichloroacetate attenuates the stemness of colorectal cancer cells via trigerring ferroptosis through sequestering iron in lysosomes.

Colorectal cancer stem cell (CSC) has been regarded to be the root of colorectal cancer progression. However, there is still no effective therapeutic method targeting colorectal CSC in clinical application. Here, we investigated the effects of dichloroacetate (DCA) on colorectal cancer cell stemness. We showed that DCA could reduce colorectal cancer cell stemness in a dose-dependent manner, which is evident by the decreased expression of stemness markers, tumor cell sphere-formation and cell migration ability. In addition, it was found that DCA trigerred the ferroptosis of colorectal CSC, which is characterized as the upregulation of iron concentration, lipid peroxides, and glutathione level, and decreased cell viability. Mechanistic studies demonstrated that DCA could sequester iron in lysosome and thus trigger ferroptosis, which is necessary for DCA-mediated attenuation on colorectal cancer cell stemness. Taken together, this work suggests that DCA might be a colorectal CSC-killer.

One-layer versus two-layer duct-to-mucosa pancreaticojejunostomy after pancreaticoduodenectomy: study protocol for a randomized controlled trial.

BACKGROUND: Although various pancreaticojejunal duct-to-mucosa anastomosis methods have been developed to reduce the postoperative risks of pancreaticoduodenectomy, pancreatic fistula remains the most serious complication with a high incident rate. The aim of this study is to compare the safety and effectiveness of one-layer and two-layer duct-to-mucosa pancreaticojejunostomy in patients undergoing pancreaticoduodenectomy. METHODS/DESIGN: In this study, adult patients who sign consent forms will be recruited and scheduled for elective pancreaticoduodenectomy. One hundred and fourteen patients will be included and randomized before pancreaticojejunal reconstruction and after resection of the lesion from the pancreatic or periampullary region. The primary efficacy endpoint is the incident rate of postoperative pancreatic fistula. Statistical analysis will be based on the intention-to-treat population. Patients will be followed up for 3 months by monitoring for complications and other adverse events. DISCUSSION: This prospective, single-center, randomized, single-blinded, two-group parallel trial is designed to compare one-layer with two-layer duct-to-mucosa anastomosis for pancreaticojejunal anastomosis during elective pancreaticoduodenectomy. TRIAL REGISTRATION: Clinical Trials.gov: NCT02511951 . Registered on 29 July 2015.