Serum Creatinine and Amylase in Drain to Predict Pancreatic Fistula Risk after Pancreatoduodenectomy.

INTRODUCTION: The identification of patients with low risk of clinically relevant postoperative pancreatic fistula (CR-POPF) and postoperative hemorrhage (PPH) can guide drain removal after pancreatoduodenectomy (PD). However, drain fluid amylase (DFA) ≤5,000 U/L on postoperative day (POD) 1 does not robustly predict the absence of CR-POPF. METHODS: Consecutive patients undergoing PD at Sun Yat-sen University Cancer Center between July 2018 and October 2021 were analyzed. Recursive partitioning analysis was used to classify patients into groups with different risks of CR-POPF and PPH. RESULTS: Among 288 consecutive patients included, 99 patients (34.38%) developed CR-POPF (86 grade B and 13 grade C). Patients with CR-POPF had increased levels of preoperative creatinine (CRE) and POD1 CRE. The combination of POD1 CRE (>104 µmol/L or not) and POD1 DFA (>5,000 U/L or not) stratified patients into subgroups with the maximum difference in CR-POPF risk. The CR-POPF rates were 17.82% (36/202) in group A (POD1 CRE ≤104 µmol/L and POD1 DFA ≤5,000 U/L), 53.33% (8/15) in group B (POD1 CRE >104 µmol/L and POD1 DFA ≤5,000 U/L), and 77.46% (55/71) in group C (POD1 DFA >5,000 U/L). The PPH rates were 1.98% (4/202), 20.00% (3/15), and 19.72% (14/71) in groups A, B, and C, respectively. CONCLUSION: Patients with POD1 DFA ≤5,000 U/L and POD1 CRE >104 µmol/L have a high risk of CR-POPF and may not benefit from early drain removal. Patients with POD1 DFA ≤5,000 U/L and POD1 CRE ≤104 µmol/L have low risk of CR-POPF and PPH.

Enhanced simultaneous partial nitrification and denitrification performance of aerobic granular sludge via tapered aeration in sequencing batch reactor for treating low strength and low COD/TN ratio municipal wastewater.

The aerobic granular sludge simultaneous partial nitrification, denitrification and phosphorus removal (AGS-SPNDPR) process was carried out via tapered aeration in sequencing batch reactor (SBR) for treating low strength and low COD/TN ratio municipal wastewater. The results showed that aerobic granular sludge was successfully cultivated with good sedimentation performance when treating the municipal wastewater. Meanwhile, the median granule size increased to 270 (R1) and 257 (R2) µm on day 80. The excellent removal performance of COD (92%) and NH4+-N (95%) were achieved under different aeration modes, while the higher TN removal efficiency (76%) was achieved by tapered aeration. The accumulation of NO2--N in R2 indicated that the tapered aeration was beneficial to achieve simultaneously partial nitrification and denitrification. Meanwhile, the high-efficiency phosphorus (95%) removal was realized via additional carbon source, and SPNDPR process was formed under tapered aeration. The bacterial community analysis indicated denitrifying glycogen-accumulating organisms (DGAOs) Candidatus_Competibacter and ammonia-oxidizing bacteria (AOB) Nitrosomonas were more effectively enriched via tapered aeration, while phosphorus-accumulating organisms (PAOs) Candidatus_Accumulibacter were effectively enriched under additional organic carbon. AOB, denitrifying bacteria and PAOs were simultaneously enriched by tapered aeration and additional carbon source, which was beneficial to nutrients removal. This study might be conducive to the application of AGS-SPNDPR system for treating low strength and low COD/TN ratio municipal wastewater under tapered aeration.

LINC00460 promotes pancreatic cancer progression by sponging miR-491-5p.

BACKGROUND: A growing body of studies have suggested that LINC00460 is instrumental in tumorigenesis and tumour progression. Nonetheless, the biological function and mechanisms of LINC00460 in pancreatic ductal adenocarcinoma (PDAC) remain vague. METHODS: Analysis based on public databases and a quantitative reverse transcription-polymerase chain reaction were performed to screen for differentially expressed lncRNAs in PDAC and to detect LINC00460 expression in PDAC cell lines and clinical samples. The survival of patients in the up-regulated and down-regulated LINC00460 expression groups was compared by using the Kaplan-Meier method. In addition, the potential biological functions of LINC00460 in PDAC were explored by cell counting kit-8, colony formation, flow cytometry and transwell assays. Furthermore, bioinformatics analysis, luciferase reporter assays and rescue experiments were applied to demonstrate the mechanism by which LINC00460 could directly bind to and inhibit miR-491-5p. RESULTS: LINC00460 is up-regulated in PDAC and correlates with adverse survival outcomes. The results of functional tests verified that LINC00460 knockdown inhibited both cell proliferation and cell migration. Additionally, knockdown led to G0/G1 cell cycle blockage and enhanced cell apoptosis. Mechanistic investigations revealed that LINC00460 directly binds to and attenuates the tumour suppressor miR-491-5p, thus accelerating PDAC progression. CONCLUSIONS: This research showed that LINC00460 is overexpressed in PDAC and correlates with adverse clinical outcomes. Additionally, LINC00460 promotes the aggressiveness of PDAC by targeting miR-491-5p. Thus, LINC00460 may serve as diagnostic biomarker of PDAC and a new target for PDAC therapy.

Induced CD10 expression during monocyte-to-macrophage differentiation identifies a unique subset of macrophages in pancreatic ductal adenocarcinoma.

OBJECTIVE: Tumor associated macrophages (TAMs) promoted pancreatic ductal adenocarcinoma (PDAC) initiation and progression. In this study we aimed to evaluate CD10 expression by monocytes/macrophages and its clinical significance in PDAC. METHODS: Human CD14+ peripheral blood monocytes were isolated and cultured for 6-7 days to differentiate into macrophages in vitro. Monocytic THP-1 cells were cultured and treated with 100 ng/ml phorbol 12-myristate 13-acetate (PMA) for 72 h to induce macrophage differentiation. Reverse transcription-quantitative PCR, immunohistochemistry, immunofluorescence, multiplex immunohistochemical staining and flow cytometry were performed to detect CD10 expression. In addition, the correlations between CD10 expression and immune cells infiltration were investigated through TIMER or GEPIA. Finally, Kaplan-Meier plotter and GEPIA databases were adopted to evaluate the influence of CD10 on clinical prognosis. RESULTS: Our results indicated that CD10 was expressed by a subset of human monocytes and many more cells expressed CD10 after differentiation into macrophages in vitro (13.19% vs. 41.39%; P < 0.0001). As for PDAC tissues, CD10 was correlated with immune cells infiltration and was expressed by a subset of TAMs. For THP-1 cells, PMA could induce CD10 expression through the MAPK pathway. The Kaplan-Meier plotter results suggested that CD10 expression had an impact on the prognosis of PDAC. CONCLUSIONS: In this study we demonstrated that CD10 was expressed by human primary monocytes, human monocyte-derived macrophages and TAMs, and was correlated with poor prognosis in PDAC, suggesting CD10 to be a potential therapeutic target in PDAC.

Exploration of the Exact Prognostic Significance of Lymphatic Metastasis in Jejunoileal Neuroendocrine Tumors.

BACKGROUND: How to evaluate the prognostic significance of lymphatic metastasis in patients with small bowel (jejunoileal) neuroendocrine tumors (SBNETs) is still not conclusive. METHODS: Data for patients with SBNETs, but without distant metastasis, were retrieved from the Surveillance, Epidemiology, and End Results database. Recursive partitioning analysis (RPA) was used for classification development by combining examined lymph nodes (ELNs) and lymph node ratio (LNR). RESULTS: Overall, 1925 patient records were retrieved. Patients with N0 and N1 disease (based on the definition of the European Neuroendocrine Tumor Society [ENETS] staging classification) did not have different OS (p = 0.7867), nor did patients with N0, N1 (< 12 positive nodes), and N2 (≥ 12 positive nodes) disease based on the definition of American Joint Committee on Cancer (AJCC) 8th edition staging classification (p = 0.5276). However, Cox regression analysis indicated that both ELNs (hazard ratio [HR] 0.968, 95% confidence interval [CI] 0.949-0.987; p = 0.0013) and LNR (HR 2.288, 95% CI 1.122-3.682; p = 0.0006) were prognostic factors. Using RPA, we combined ELNs and LNR, and patients were reclassified into three groups (group 1: ELNs ≥ 12, any LNR; group 2: ELNs < 12, LNR < 0.35; group 3: ELNs < 12, LNR ≥ 0.35). Survival analysis and multivariate Cox regression showed that groups 1, 2, and 3 had progressively worse survival. Furthermore, we found that ELNs ≥ 12 could remarkably improve patient survival (p < 0.001). CONCLUSIONS: The current definition of lymphatic metastasis could not help predict patient survival. Our newly proposed classification of lymphatic metastasis is better than the ENETS and AJCC 8th edition staging classifications in evaluating the prognostic significance of lymphatic metastasis in SBNETs. Systematic resection of lymph nodes (≥ 12) could help improve patient survival.

ComProliM: A cell growth assay robust to initial cell number in co-culture system.

Cell growth is conventionally quantified using CCK-8 or MTT assays, but these methods display considerable sensitivity to initial cell quantities. Inherent sampling errors during cell counting and seeding make it impossible to achieve an absolute equivalence of initial cell numbers, potentially confounding the results of CCK-8 or MTT assays. In the present study, we introduce a novel cell proliferation assay, ComProliM, predicated on cell competition theory. Both numeral simulations and empirical testing demonstrate that ComProliM index (CPMI) reliably represents cell growth rate and is not influenced by variations in initial cell number. Intriguingly, two adherent cells of differing fluorescence states are co-cultured, suggesting that ComProliM can be successfully employed in co-culture system cell proliferation assays, including, for instance, the exploration of subclone interactions. We anticipate ComProliM will provide a viable alternative for quantifying adherent cell growth rates, particularly in cases where conventional methodologies deliver inconsistent or ambiguous results.

Sex differences in solid pseudopapillary neoplasm of the pancreas: A population-based study.

OBJECTIVE: Solid pseudopapillary neoplasm (SPN) of the pancreas is a rare tumor. This study aims to examine the clinicopathological features and surgical treatments of SPN and compare the clinical behavior and prognosis between men and women with SPN. METHODS: We collected the population data of patients with SPN diagnosed between 2004 and 2017 from the SEER database. The Kaplan-Meier method was used to analyze overall survival (OS) and disease-specific survival (DSS), and log-rank tests were used to evaluate the differences between subgroups. Univariate and multivariate Cox regression analyses were performed to screen out prognostic risk factors of SPN. RESULTS: A total of 378 patients with SPN were included, with 246 (65.1%) female patients. 1-, 3-, and 5-year overall survival rates were 98.9%, 95.7%, and 93.7%, respectively. Survival analysis revealed that regardless of stage, patients with SPN who underwent surgical interventions still had a significantly better prognosis than those without surgical interventions (P < .001). The patients with lymphatic dissection had a significantly better prognosis than those without lymphatic dissection (P < .001). Moreover, compared with female patients, male patients had significantly poorer OS and DSS (P < .001). Female SPN showed a bimodal age-frequency distribution with early-onset incidence at 28 years and late-onset peak incidence at 62 years, while male SPN presented a unimodal distribution with peak incidence at approximately age 64 years. In female patients, the tumor size in premenopausal females (<65 years old) was significantly larger than that in postmenopausal females (≥65 years old) (P < .001). Clinicopathological characteristic profiles were different not only between male SPN and premenopausal female SPN but also between premenopausal and postmenopausal female SPN. CONCLUSION: SPN presents indolent behavior and predominantly occurs in young women. Regardless of stage, surgical intervention is recommended. Moreover, our study is the first large enough study to demonstrate sex-related discrepancies in SPN. Thus, different treatment strategies should be designed for patients of different sexes at different ages and hormone therapy is a promising approach for SPN.

A Novel Prognostic Nomogram for Patients With Recurrence of Intrahepatic Cholangiocarcinoma After Initial Surgery.

Background: The prognosis of patients with post-operative recurrent intrahepatic cholangiocarcinoma (ICC) is at great variance. We aimed to propose a novel efficient prognostic nomogram in facilitating the risk stratification for post-operative recurrent ICC patients. Methods: From 2000 to 2016, a total of 237 post-operative recurrent ICC patients were enrolled in this study, and randomly divided into training (n = 178) and validation cohorts (n = 59) at a ratio of 3:1. The performance of this nomogram was assessed by discrimination, calibration, and clinical usefulness, and the results were compared with four other currently used ICC staging systems. Results: On multivariate analysis of the training cohort, serum CA 19-9, albumin-bilirubin grade at recurrence, time from primary resection to recurrence, tumor number at recurrence, and treatment for recurrence were selected for the model. The concordance index (C-index) of our model was 0.791 [95% confidence interval (CI), 0.736-0.846], which was statistically higher than the values of the following systems: American Joint Committee on Cancer (AJCC) 8th edition (0.610), Liver Cancer Study Group of Japan (0.613), Nathan (0.582), and Okabayashi (0.600; P < 0.001 for all). The nomogram performed well in terms of calibration when compared with actual observation. The findings were supported by the validation cohort. Conclusions: Compared with four currently used staging systems for ICC, our nomogram showed more promising clinical utility in improving individualized predictions of survival for post-operative recurrent ICC patients.

SYPL1 Inhibits Apoptosis in Pancreatic Ductal Adenocarcinoma via Suppression of ROS-Induced ERK Activation.

Synaptophysin-like 1 (SYPL1) is a neuroendocrine-related protein. The role of SYPL1 in pancreatic ductal adenocarcinoma (PDAC) and the underlying molecular mechanism remain unclarified. Here, after analyzing five datasets (GSE15471, GSE16515, GSE28735, TCGA, and PACA-AU) and 78 PDAC patients from Sun Yat-sen University Cancer Center, we demonstrated that SYPL1 was upregulated in PDAC and that a high level of SYPL1 indicated poor prognosis. Bioinformatics analysis implied that SYPL1 was related to cell proliferation and cell death. To validate these findings, gain-of-function and loss-of-function experiments were carried out, and we found that SYPL1 promoted cell proliferation in vitro and in vivo and that it protected cells from apoptosis. Mechanistic studies revealed that sustained extracellular-regulated protein kinase (ERK) activation was responsible for the cell death resulting from knockdown of SYPL1. In addition, bioinformatics analysis showed that the expression of SYPL1 positively correlated with antioxidant activity. Reactive oxygen species (ROS) were upregulated in cells with SYPL1 knockdown and vice versa. Upregulated ROS led to ERK activation and cell death. These results suggest that SYPL1 plays a vital role in PDAC and promotes cancer cell survival by suppressing ROS-induced ERK activation.

Integrated sulfur- and iron-based autotrophic denitrification process and microbial profiling in an anoxic fluidized-bed membrane bioreactor.

The integrated sulfur- and Fe0-based autotrophic denitrification process in an anoxic fluidized-bed membrane bioreactor (AnFB-MBR) was developed for the nitrate-contaminated water treatment in order to control sulfate generation and avoid alkalinity supplement. The nitrate removal rate of the AnFB-MBR reached 1.22 g NO3--N L-1d-1 with NO3--N ranging 40-200 mg L-1 at hydraulic retention times of 1.0-5.0 h. The denitrification in the integrated system was simultaneously carried out by sulfur- and Fe0-oxidizing autotrophic denitrifiers. The effluent sulfate generation was decreased by 29.3-70.3% and 31.2-50.9% due to the functional role of Fe0-based denitrification in the integrated system. Alkalinity produced by Fe0-oxidizing autotrophic denitrification could compensate for the alkalinity consumption by sulfur-based autotrophic denitrification. The sulfur- and Fe0-oxidizing autotrophic denitrifying bacterial consortium was composed mainly of bacteria from Thiobacillus, Sulfurimonas, and Geothrix genera. The integrated modes leads to a harmonious co-existence of sulfur- and Fe0-oxidizing denitrifying microbes, which may make a difference to the functional performance of the bioreactor. Overall, the integrated sulfur- and Fe0-based autotrophic denitrification could overcome the shortcomings of excess sulfate generation and external alkalinity supplementation compared to the sole sulfur-based autotrophic denitrification, indicating further potential for the technology in practice.

Preoperative CEA levels are supplementary to CA19-9 levels in predicting prognosis in patients with resectable intrahepatic cholangiocarcinoma.

Background: There are few diagnostic tools that can be used to determine which patient with intrahepatic cholangiocarcinoma (ICC) can benefit from surgery actually, highlighting that the need for new preoperative stratification strategies. The aim of this study was to investigate the predictive values of preoperative biomarkers in survival analyses for patients with ICC after surgical resection. Methods: A total of 285 patients with ICC were retrospectively reviewed. Receiver operating charateristics (ROC) curves were used to evaluate the predictive effects of preoperative carbohydrate antigen 19-9 (CA19-9) with different cutoff values and carcinoembryonic antigen (CEA) in patients with ICC. Results: Preoperative CA19-9 with a cutoff value of 200 U/ml performed better in predicting overall survival (OS) and progression free survival (PFS) in ICC patients. Patients with preoperative CA19-9 value > 200 U/ml generally had a poor surgical response. However, surgical resection could also benefit patients whose CA19-9 levels decreased postoperatively or preoperative CEA levels were negative. Conclusions: With the cutoff value of 200U/ml, CA19-9 was a better preoperative biomarker for predicting survival for ICC patients after surgical resection. Combination of preoperative CA19-9 and CEA showed the strongest predictive power in survival analyses in these patients and should be recognized in daily clinical care.

A Refined Staging Model for Resectable Pancreatic Ductal Adenocarcinoma Incorporating Examined Lymph Nodes, Location of Tumor and Positive Lymph Nodes Ratio.

Background: Nodal status and tumor site are prognostic factors for resectable pancreatic ductal adenocarcinoma (PDAC). Parameters for nodal status are diverse, and the number of examined lymph nodes (eNs) needed for good prognosis are uncertain. We try to modify staging system of resectable PDAC with parameters mentioned above by recursive partitioning analysis. Methods: Patients from the Surveillance, Epidemiology, and End Results (SEER) database were divided into training cohort and internal validation cohort, randomly. PDAC patients from Sun Yat-sen University Cancer Center were regarded as external validation cohort. The training cohort was used to refine staging model by recursive partitioning analysis, while the internal validation cohort and the external validation cohort were applied to assess discriminatory capacity of staging model. For parameters included in the modified model, their effects were studied. Results: The number of eNs, tumor site and tumor size were risk factors for positive nodal status. Lymph nodes ratio (LNR), tumor site, eNs and T stages of 8th the American Joint Committee on Cancer (AJCC) were selected to develop a refined model, dividing patients into 5 groups of different outcomes, preceding 8th AJCC classification. Besides, we found that (1) for small PDAC (diameter < 1cm), lymph node metastasis was rarely found; (2) enough eNs were needed to ensure better prognosis of node-negative patients; (3) tumors in the head of pancreas were prone to lymph nodes metastasis; (4) for node-positive patients, LNR was a better nodal parameter compared to positive lymph nodes (pNs). Conclusion: Our improved staging system helps to illuminate the interactions among tumor site, size and eNs.

The Predictive Value of Staging Systems and Inflammation Scores for Patients with Combined Hepatocellular Cholangiocarcinoma After Surgical Resection: a Retrospective Study.

BACKGROUND: Combined hepatocellular cholangiocarcinoma (cHCC-CC) is a rare form of primary liver tumor. A specific staging system for predicting survival in patients with cHCC-CC is not available. The aim of the present study was to evaluate the ability of staging systems and inflammation-based scores to predict overall survival (OS) and progression-free survival (PFS) of patients with cHCC-CC after surgical resection. METHODS: The data from 99 patients with cHCC-CC after surgical resection from June 2000 and January 2017 were retrospectively collected. Patients were allocated into HCC (hepatocellular carcinoma)-dominant (IHD) group and ICC (intrahepatic cholangiocarcinoma)-dominant (IID) group based on radiological characteristics. Similarly, patients were also divided into HCC-dominant (PHD) group and ICC-dominant (PID) group based on pathological characteristics. Univariate and multivariate analyses were performed to identify variables associated with OS and PFS. The prognostic value of staging systems and inflammation-based scores were analyzed and compared using receiver operating characteristic (ROC) curves. RESULTS: The 1-, 2-, and 3-year OS rates were 82.6, 66.3, and 59.6%, respectively. The 1-, 2-, and 3-year PFS rates were 52.2, 38.1, and 31.5%, respectively. Independent prognostic factors identified by multivariate analyses included HCC-TNM staging system and tumor diameter both for OS and PFS analyses. HCC-TNM staging system displayed higher area under ROC curve (AUC) values than the other staging systems or inflammation-based scores. CONCLUSIONS: HCC-TNM staging system was able to adequately predict prognosis of patients with cHCC-CC after surgical resection, especially for patients with HCC-dominant characteristics in clinical practice.