Background
Postoperative complication rates after laparoscopic pancreaticoduodenectomy (LPD) remain high despite improvements in perioperative management. Measurements on computed tomography imaging ...of intra-abdominal tissue have not been thoroughly investigated as predictors of mortality and morbidity following LPD. The aim of this study was to assess whether the ratio of abdominal depth and body mass index (AD/BMI ratio) could predict postoperative complications following LPD.
Methods
We retrospectively analyzed 231 patients who underwent LPD and had a computed tomography scan between 2014 and 2018. Demographic, radiologic, and pathologic data were correlated to the occurrence of postoperative complications. Propensity score matching was performed to minimize selection biases associated with the comparison of retrospective data between the high and low AD/BMI ratio groups. Univariate and multivariate analyses were also performed to assess the risk factors for postoperative complications.
Results
Of the 102 patients identified for propensity score matching analysis, 29 patients (28.4%) experienced postoperative complications. Patients with a high AD/BMI ratio had a higher prevalence of overall complications (45.1% vs. 11.8%,
P
< 0.001), postoperative pancreatic fistula (17.6% vs. 2.00%,
P
= 0.008), delayed gastric emptying (33.3%
vs
. 3.90%,
P
< 0.001), and intra-abdominal abscess (17.6% vs. 0,
P
= 0.002). In the multivariate analysis, an AD/BMI ratio greater than 2.7 (m
3
/kg·10
3
; OR = 6.16, 95% confidence interval 1.04–36.4,
P
= 0.045) was the only independent predictive factor of postoperative complications.
Conclusions
The preoperative AD/BMI ratio is a predictor of postoperative complications following LPD.
Abstract
Background
Pancreatic cancer is one of the most lethal human cancers.
N
6
-methyladenosine (m
6
A), a common eukaryotic mRNA modification, plays critical roles in both physiological and ...pathological processes. However, its role in pancreatic cancer remains elusive.
Methods
LC/MS was used to profile m
6
A levels in pancreatic cancer and normal tissues. Bioinformatics analysis, real-time PCR, immunohistochemistry, and western blotting were used to identify the role of m
6
A regulators in pancreatic cancer. The biological effects of methyltransferase-like 14 (METTL14), an mRNA methylase, were investigated using in vitro and in vivo models. MeRIP-Seq and RNA-Seq were used to assess the downstream targets of METTL14.
Results
We found that the m
6
A levels were elevated in approximately 70% of the pancreatic cancer samples. Furthermore, we demonstrated that METTL14 is the major enzyme that modulates m
6
A methylation (frequency and site of methylation). METTL14 overexpression markedly promoted pancreatic cancer cell proliferation and migration both in vitro and in vivo
,
via direct targeting of the downstream
PERP
mRNA (p53 effector related to PMP-22) in an m
6
A-dependent manner. Methylation of the target adenosine lead to increased
PERP
mRNA turnover, thus decreasing PERP (mRNA and protein) levels in pancreatic cancer cells.
Conclusions
Our data suggest that the upregulation of METTL14 leads to the decrease of PERP levels via m
6
A modification, promoting the growth and metastasis of pancreatic cancer; therefore METTL14 is a potential therapeutic target for its treatment.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Gemcitabine is the first-line treatment for patients with pancreatic cancer (PC), yet most patients develop resistance to gemcitabine. Recent studies showed that circular RNAs (circRNAs) have ...important regulatory roles in PC progression and chemoresistance. In this study, the ability of circRNA circ_0092367 to enhance gemcitabine efficacy was tested and the underlying molecular mechanism of circ_0092367 was investigated. The expression levels of circ_0092367, miR-1206, and ESRP1 were measured using qRT-PCR experiments. The effects of circ_0092367, miR-1206, and ESRP1 on PC cell lines exposed to gemcitabine were examined by CCK-8 assays. We performed luciferase assays to determine the relationship between circ_0092367 and miR-1206 and between miR-1206 and ESRP1. We demonstrated that circ_0092367 was significantly downregulated in PC tissues and cell lines, and a high expression of circ_0092367 was associated with improved survival in patients with PC. Gain- and loss-of-function assays revealed that circ_0092367 inhibited epithelial-mesenchymal transition (EMT) phenotypes and sensitized PC cells to gemcitabine treatment in vitro and in vivo. Cytoplasmic circ_0092367 could directly repress the levels of miR-1206 and thus upregulate the expression of ESRP1, thereby inhibiting EMT and enhancing the sensitivity of PC cells to gemcitabine treatment. Our findings show that circ_0092367 plays a crucial role in sensitizing PC cells to gemcitabine by modulating the miR-1206/ESRP1 axis, highlighting its potential as a valuable therapeutic target in PC patients.
Background and purpose
A new noninvasive biomarker is being sought to predict the prognosis of patients with pancreatic cancer. Red-cell volume distribution width (RDW), a descriptive parameter for ...erythrocyte variation, has been shown to have prognostic value for some tumor types. Our purpose was to assess the RDW value to predict the prognosis of patients with pancreatic cancer.
Methods
The subjects of this retrospective study were 792 patients who underwent radical surgery for pancreatic cancer, divided into high-RDW and low-RDW groups based on receiver operating characteristic (ROC) curve analysis (15.6%). The controlling nutritional status (CONUT) score was used to assess preoperative nutritional status. Statistical analysis was conducted to investigate the differences between the high and low RDW groups, and to explore the possibility of the RDW being used as prognostic predictor for patients with pancreatic cancer.
Results
The immune-nutritional status was worse in the high-RDW group than in the low-RDW group. The high-RDW group patients also had a poorer prognosis. Risk factor analysis showed that the RDW could be an independent risk factor for pancreatic cancer.
Conclusions
The RDW is associated with immune-nutritional status in pancreatic cancer patients and can be used as an independent prognostic factor for their postoperative survival.
Despite the worldwide application of various terminological and classification systems used for pancreatic cancer, such as UICC classification and JPS classification based on the TNM system, however, ...little information on their use in operative decision-making is available. A new classification system according to the relationship with the tumor and key vasculature around the pancreas is described, and the pancreatic carcinomas are divided into eight types to provide operative decisions for different types of pancreatic cancer. Furthermore, the relationship between the classification system and TNM system is discussed. The new classification is the first time to discuss the classification for the operative decisions for the pancreatic cancer and this formalized type of approach may provide the best chance of achieving R0 resection and providing improved safety results.
/Objective: As a new immune-nutritional marker, the controlled nutritional status (CONUT) score has been reported to predict the prognosis of cancer patients. We aimed to elucidate the prognostic ...value of preoperative CONUT score in pancreatic cancer patients undergoing radical surgery, and to construct a nomogram based on CONUT score to predict individual survival.
Preoperative CONUT scores were calculated prospectively in 382 patients with pancreatic cancer who underwent radical surgery. Evaluated the relationship between CONUT score and pancreatic cancer prognosis. Cox proportional hazard models were used to determine predictors of survival and a new nomogram was established to predict pancreatic cancer overall survival (OS).
The area under curve of CONUT score was higher than other immune-nutritional indexes. The OS of the high-CONUT group were significantly lower than that of low-CONUT group. Multivariate analysis showed that CONUT score, gender, AJCC stage, complications and reoperation were independent prognostic factors for OS. Nomogram based on these variables has better discriminant ability in predicting survival compared with other traditional staging systems.
Preoperative CONUT score is an effective independent predictor of OS in pancreatic cancer patients undergoing radical surgery. This new CONUT based nomogram provides accurate, individualized survival prediction for pancreatic cancer.
Dysfunction in long noncoding RNAs (lncRNAs) is reported to participate in the initiation and progression of human cancer; however, the biological functions and molecular mechanisms through which ...lncRNAs affect pancreatic cancer (PC) are largely unknown. Here, we report a novel lncRNA, LINC01111, that is clearly downregulated in PC tissues and plasma of PC patients and acts as a tumor suppressor. We found that the LINC01111 level was negatively correlated with the TNM stage but positively correlated with the survival of PC patients. The overexpression of LINC01111 significantly inhibited cell proliferation, the cell cycle, and cell invasion and migration in vitro, as well as tumorigenesis and metastasis in vivo. Conversely, the knockdown of LINC01111 enhanced cell proliferation, the cell cycle, and cell invasion and migration in vitro, as well as tumorigenesis and metastasis in vivo. Furthermore, we found that high expression levels of LINC01111 upregulated DUSP1 levels by sequestering miR-3924, resulting in the blockage of SAPK phosphorylation and the inactivation of the SAPK/JNK signaling pathway in PC cells and thus inhibiting PC aggressiveness. Overall, these data reveal that LINC01111 is a potential diagnostic biomarker for PC patients, and the newly identified LINC01111/miR-3924/DUSP1 axis can modulate PC initiation and development.
MicroRNAs have been reported to play an important role in tumor development and progression by targeting oncogenes and tumor suppressors. miR-23a has been described as significantly upregulated in ...multiple cancers and involved in tumorigenesis. The aim of this study was to evaluate the potential roles of miR-23a in pancreatic ductal adenocarcinoma (PDAC). We found that miR-23a level was significantly increased in tissues of PDAC compared with that in the control by real-time PCR. FOXP2 expression was downregulated and inversely correlated with miR-23a. miR-23a directly targeted the 3'-untranslated region of FOXP2 mRNA and repressed its expression. Mechanistically, enhancement of miR-23a by transfection with mimics in Aspc-1 cells significantly promoted cell proliferation and invasion, while miR-23a inhibitors transfection in SW1990 cells induced an inhibitory effect. Moreover, restoration of FOXP2 impaired the pro-proliferation and proinvasion effects of miR-23a, indicating FOXP2 is a direct mediator of miR-23a functions. In conclusion, our findings suggest a novel miR-23a/FOXP2 link contributing to PDAC development and invasion. It may be a potential diagnostic and therapeutic target for PDAC.
Background
Pancreatic cancer (PC) is a digestive tract malignancy with poor prognosis. Long noncoding RNA (lncRNA) OPA interacting protein 5 antisense RNA 1 (OIP5-AS1) was regarded to be correlated ...with human malignancy, working as tumor suppressor or promoter on the basis of tumor types. However, the function of OIP5-AS1 in PC remained unclear.
Aims
The study focused on the function and regulatory mechanism of OIP5-AS1 in PC.
Methods
OIP5-AS1 expression was assessed by the quantitative reverse transcription PCR (RT-qPCR) in tumor tissues and PC cell lines. 5-ethynyl-2′-deoxyuridine (EdU) incorporation and cell counting kit-8 (CCK-8) assays were applied to detect cell proliferation ability. Through wound healing and transwell assays, cell migration and invasion capacities were estimated. Flow cytometry analysis was performed to examine apoptosis capability of PC cells.
Results
OIP5-AS1 downregulating inhibited cell proliferation, migration, and invasion capacities, while promoting cell apoptosis rates. As a competing endogenous RNA (ceRNA), OIP5-AS1 competed with Forkhead Box M1 (FOXM1) for the binding sites on microRNA-320b (miR-320b). OIP5-AS1 was able to upregulate FOXM1 expression via silencing miR-320b. Furthermore, FOXM1 served as an activator of Wnt/β-catenin pathway and mediated the effect of OIP5-AS1 on Wnt/β-catenin pathway.
Conclusion
OIP5-AS1 expedites the proliferative, migrated, and invasive capability of PC cells, while repressing cell apoptosis through regulating miRNA-320b/FOXM1 axis and FOXM1/Wnt/β-catenin pathway in PC. OIP5-AS1 regulation on FOXM1/Wnt/β-catenin pathway may offer novel efficient markers for PC treatments.
Background
Curative resection of hilar cholangiocarcinoma (HC) is typically carried out using open surgery. In the present study, we examined the safety (postoperative complication) and effectiveness ...(resection margin status and patient survival) of minimally invasive surgery (MIS) for HC.
Methods
This retrospective analysis included 158 patients receiving MIS for HC at 10 participating centers between December 2013 and November 2019. Patient demographics, surgical outcomes, and oncological outcomes were retrospectively analyzed.
Results
Clinical information obtained from 10 different clinical centers did not show any evident cohort-bias clustering. One hundred and twenty-six (79.7%) patients underwent LRHC, 12 (7.6%) patients underwent RARHC, conversion to an open procedure occurred in 20 (12.7%) patients. The operation time and estimated blood loss were 410.8 ± 128.9 min and 477.8 ± 706.3 mL, respectively. The surgical radicality of the 158 patients was R0, 129 (81.6%); R1, 20 (18.4%) and R2, 9 (5.7%). Grades I–II complications was occurred in 68 (43.0%) patients. Severe morbidity (grade III–V) occurred in 14 (8.7%) patients. The median overall survival in whole cohort was 25.4 months. The overall survival rate was 67.6% at year 1, 28.8% at year 3, and 19.2% at year 5. Comparing the first half of MISHC performed by each center with the following cases, the operation time and postoperative hospital stay does not decrease with the increasing cases. On literature review, MISHC is non-inferior to open surgery at least in perioperative period.
Conclusions
In this Chinese MIS for HC multicenter study, the largest to date, long-term overall survival rates after MIS appear comparable to those reported in current open series. Further randomized controlled trials are necessary to assess the global impact of MISHC.
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