ZFHX3 methylation in peripheral blood monocytes as a potential biomarker for pancreatic cancer detection.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is the digestive malignancy with poor prognosis, and there is still a lack of effective diagnostic biomarkers. OBJECTIVE: We aimed to explore the diagnostic efficiency of DNA methylation in peripheral blood monocytes (PBMCs) in PDAC. METHODS: 850K BeadChips were used to detect genome-wide methylation of PBMCs. For the selected sites, MethylTarget assays was used for further verification. The support vector machine was used to establish the combined panel. RESULTS: A total of 167 PDAC patients and 113 healthy controls were included in this study and were divided into three sets. In the discovery set, we found 4625 differentially methylated positions (DMPs) between cancer group and healthy controls. ZFHX3 (0.16 ± 0.04 vs. 0.18 ± 0.04, P = 0.001), cg01904886 (0.84 ± 0.05 vs. 0.81 ± 0.04, P = 0.02) and NUMBL (0.96 ± 0.005 vs. 0.957 ± 0.005, P = 0.04) were found to be significantly different in training set. The locus with more significant differences, namely ZFHX3, was used for further validation and to establish a combined diagnostic panel with CA19-9. In the validation set, the ROC curve indicated that the AUC value of ZFHX3 was 0.75. The AUC value of the combined model (AUC = 0.92) was higher than that of CA19-9 alone (AUC = 0.88). In patients with normal CA19-9 levels, the ZFHX3 methylation biomarker still maintained good diagnostic efficacy (AUC = 0.71). CONCLUSION: Our study preliminarily suggests that ZFHX3 methylation combined with CA19-9 can improve the detection rate of PDAC. Especially in patients with normal CA19-9, ZFHX3 methylation can maintain stable diagnostic efficacy. The diagnostic value of ZFHX3 methylation still needs to be prospectively validated.

Chromatin accessibility uncovers KRAS-driven FOSL2 promoting pancreatic ductal adenocarcinoma progression through up-regulation of CCL28.

BACKGROUND: The epigenetic mechanisms involved in the progression of pancreatic ductal adenocarcinoma (PDAC) remain largely unexplored. This study aimed to identify key transcription factors (TFs) through multiomics sequencing to investigate the molecular mechanisms of TFs that play critical roles in PDAC. METHODS: To characterise the epigenetic landscape of genetically engineered mouse models (GEMMs) of PDAC with or without KRAS and/or TP53 mutations, we employed ATAC-seq, H3K27ac ChIP-seq, and RNA-seq. The effect of Fos-like antigen 2 (FOSL2) on survival was assessed using the Kaplan-Meier method and multivariate Cox regression analysis for PDAC patients. To study the potential targets of FOSL2, we performed Cleavage Under Targets and Tagmentation (CUT&Tag). To explore the functions and underlying mechanisms of FOSL2 in PDAC progression, we employed several assays, including CCK8, transwell migration and invasion, RT-qPCR, Western blotting analysis, IHC, ChIP-qPCR, dual-luciferase reporter, and xenograft models. RESULTS: Our findings indicated that epigenetic changes played a role in immunosuppressed signalling during PDAC progression. Moreover, we identified FOSL2 as a critical regulator that was up-regulated in PDAC and associated with poor prognosis in patients. FOSL2 promoted cell proliferation, migration, and invasion. Importantly, our research revealed that FOSL2 acted as a downstream target of the KRAS/MAPK pathway and recruited regulatory T (Treg) cells by transcriptionally activating C-C motif chemokine ligand 28 (CCL28). This discovery highlighted the role of an immunosuppressed regulatory axis involving KRAS/MAPK-FOSL2-CCL28-Treg cells in the development of PDAC. CONCLUSION: Our study uncovered that KRAS-driven FOSL2 promoted PDAC progression by transcriptionally activating CCL28, revealing an immunosuppressive role for FOSL2 in PDAC.

Diagnostic role and prognostic value of tumor markers in high-grade gastro-enteropancreatic neuroendocrine neoplasms.

OBJECTIVES: High-grade gastro-enteropancreatic neuroendocrine neoplasms (GEP-NENs) are a heterogeneous group of rare tumors of two different types: well differentiated neuroendocrine tumors grade 3 (NETs G3) and poorly differentiated neuroendocrine carcinomas (NECs). This study aimed to explore the value of eight common preoperative markers in differentiating NETs G3 from NECs and the prognosis prediction of high-grade GEP-NENs. METHODS: Seventy-two patients diagnosed with high-grade GEP-NENs who underwent surgery at our institution were recruited for this study. Demographic and clinicopathological characteristics, preoperative serum tumor markers, and survival data were collected and analyzed. Kaplan-Meier methods were used to analyze survival rates, and a Cox regression model was used to perform multivariate analyses. RESULTS: Serum carcinoembryonic antigen (CEA) was dramatically higher in NECs than in NETs G3 (P = 0.025). After follow-up, 57 of the 72 patients remained for survival analysis. Elevated serum carbohydrate antigen 19-9 (CA19-9), CEA, cancer antigen 125 and sialic acid (SA) levels indicated poorer survival of high-grade GEP-NEN patients. Only CA19-9 (HR: 6.901, 95% CI: 1.843 to 25.837, P = 0.004) was regarded as an independent risk factor for overall survival. Serum CA19-9 (HR: 4.689, 95% CI: 1.127 to 19.506, P = 0.034) was also regarded as an independent factor for overall survival in NECs. CONCLUSIONS: Serum CEA levels can be used to distinguish NETs G3 from NECs. Preoperative CA19-9, CEA, cancer antigen 125 and SA levels have predictive value in the prognosis of high-grade GEP-NENs. Preoperative CA19-9, neuron-specific enolase, and SA levels can predict the prognosis of NECs.

Zinc-Dependent Regulation of ZEB1 and YAP1 Coactivation Promotes Epithelial-Mesenchymal Transition Plasticity and Metastasis in Pancreatic Cancer.

BACKGROUND: Pancreatic cancer is characterized by extensive metastasis. Epithelial-mesenchymal transition (EMT) plasticity plays a critical role in tumor progression and metastasis by maintaining the transition between EMT and mesenchymal-epithelial transition states. Our aim is to understand the molecular events regulating metastasis and EMT plasticity in pancreatic cancer. METHODS: The interactions between a cancer-promoting zinc transporter ZIP4, a zinc-dependent EMT transcriptional factor ZEB1, a coactivator YAP1, and integrin α3 (ITGA3) were examined in human pancreatic cancer cells, clinical specimens, spontaneous mouse models (KPC and KPCZ) and orthotopic xenografts, and 3-dimensional spheroid and organoid models. Correlations between ZIP4, miR-373, and its downstream targets were assessed by RNA in situ hybridization and immunohistochemical staining. The transcriptional regulation of ZEB1, YAP1, and ITGA3 by ZIP4 was determined by chromatin immunoprecipitation, co-immunoprecipitation, and luciferase reporter assays. RESULTS: The Hippo pathway effector YAP1 is a potent transcriptional coactivator and forms a complex with ZEB1 to activate ITGA3 transcription through the YAP1/transcriptional enhanced associate domain (TEAD) binding sites in human pancreatic cancer cells and KPC-derived mouse cells. ZIP4 upregulated YAP1 expression via activation of miR-373 and inhibition of the YAP1 repressor large tumor suppressor 2 kinase (LATS2). Furthermore, upregulation of ZIP4 promoted EMT plasticity, cell adhesion, spheroid formation, and organogenesis both in human pancreatic cancer cells, 3-dimensional spheroid model, xenograft model, and spontaneous mouse models (KPC and KPCZ) through ZEB1/YAP1-ITGA3 signaling axis. CONCLUSION: We demonstrated that ZIP4 activates ZEB1 and YAP1 through distinct mechanisms. The ZIP4-miR-373-LATS2-ZEB1/YAP1-ITGA3 signaling axis has a significant impact on pancreatic cancer metastasis and EMT plasticity.

COL17A1 facilitates tumor growth and predicts poor prognosis in pancreatic cancer.

OBJECTIVE: This study aimed to determine the role of COL17A1 in tumor progression and predict the prognosis of pancreatic cancer (PC). METHODS: RNA-seq data from The Cancer Genome Atlas and Genotype-Tissue Expression were analyzed using bioinformatics methods. "Limma" package was used to screen differentially expressed genes (DEGs). Prognostic-associated data were further analyzed using univariate Cox regression and verified using the GSE28375 and GSE62452 datasets. Protein-protein interaction (PPI) network analysis was integrated to screen for hub genes. In vitro quantitative real-time PCR (qPCR) and western blotting were used to detect gene expression. The functional attributes of PC cells were verified by wound healing assays, migration and invasion assays, Cell Counting Kit 8 (CCK8), and 5-ethynyl-2'-deoxyuridine (EdU) assay. RESULTS: On analyzing PC data, 4637 DEGs were identified. Of these, 2399 genes were upregulated and 2238 were downregulated. Through PPI network analysis, we identified that COL17A1 expression was highly correlated with poor prognosis of patients with PC. Functional attribute assays in the in vitro study showed that COL17A1 knockdown inhibited PC cell proliferation, migration, and invasion. CONCLUSIONS: According to our results, COL17A1 promotes PC cell proliferation, migration, and invasion mediated by the epithelial-mesenchymal transition (EMT) pathway. Thus, COL17A1 could be used as a prognostic marker in PC.

Phenotypic and Functional Transformation in Smooth Muscle Cells Derived from a Superficial Thrombophlebitis-affected Vein Wall.

BACKGROUND: Superficial thrombophlebitis (ST) is a frequent pathology, but its exact incidence remains to be determined. This study tested the hypothesis whether relationships exist among smooth muscle cells (SMCs) derived from ST, varicose great saphenous veins (VGSVs), and normal great saphenous veins (GSVs). METHODS: Forty-one samples of ST, VGSVs, and GSVs were collected. SMCs were isolated and cultured. Proliferation, migration, adhesion, and senescence in SMCs from the three vein walls were compared by various methods. Bax, Bcl-2, caspase-3, matrix metalloproteinase-2 (MMP-2), MMP-9, tissue inhibitor of metalloproteinase-1 (TIMP-1), and TIMP-2 messenger RNA (mRNA) and protein expressions were detected by fluorescence quantitative PCR and Western blot. RESULTS: An obvious decrease in cytoskeletal filaments was observed in thrombophlebitic vascular smooth muscle cells (TVSMCs). The quantity of proliferation, migration, adhesion, and senescence in TVSMCs was significantly higher than in varicose vascular smooth muscle cells and normal vascular smooth muscle cells (NVSMCs) (all P < 0.05). Bax and caspase-3 mRNA and protein expression were decreased, while Bcl-2 mRNA and protein expression were increased in the TVSMCs compared with the varicose vascular smooth muscle cells and the NVSMCs (all P < 0.05). MMP-2, MMP-9, TIMP-1, and TIMP-2 mRNA and protein expression were significantly increased in the TVSMCs compared with the VVGSVs and the NVSMCs (all P < 0.05). CONCLUSION: SMCs derived from ST are more dedifferentiated and demonstrate increased cell proliferation, migration, adhesion, and senescence, as well as obviously decreased cytoskeletal filaments. These results suggest that the phenotypic and functional differences could be related to the presence of atrophic and hypertrophic vein segments during the disease course among SMCs derived from ST, VGSVs, and GSVs.

ZIP4 Increases Expression of Transcription Factor ZEB1 to Promote Integrin α3ß1 Signaling and Inhibit Expression of the Gemcitabine Transporter ENT1 in Pancreatic Cancer Cells.

BACKGROUND & AIMS: Pancreatic tumors undergo rapid growth and progression, become resistant to chemotherapy, and recur after surgery. We studied the functions of the solute carrier family 39 member 4 (SLC39A4, also called ZIP4), which regulates concentrations of intracellular zinc and is increased in pancreatic cancer cells, in cell lines and mice. METHODS: We obtained 93 pancreatic cancer specimens (tumor and adjacent nontumor tissues) from patients who underwent surgery and gemcitabine chemotherapy and analyzed them by immunohistochemistry. ZIP4 and/or ITGA3 or ITGB1 were overexpressed or knocked down with short hairpin RNAs in AsPC-1 and MIA PaCa-2 pancreatic cancer cells lines, and in pancreatic cells from KPC and KPC-ZEB1-knockout mice, and pancreatic spheroids were established; cells and spheroids were analyzed by immunoblots, reverse transcription polymerase chain reaction, and liquid chromatography tandem mass spectrometry. We studied transcriptional regulation of ZEB1, ITGA3, ITGB1, JNK, and ENT1 by ZIP4 using chromatin precipitation and luciferase reporter assays. Nude mice were given injections of genetically manipulated AsPC-1 and MIA PaCa-2 cells, and growth of xenograft tumors and metastases was measured. RESULTS: In pancreatic cancer specimens from patients, increased levels of ZIP4 were associated with shorter survival times. MIA PaCa-2 cells that overexpressed ZIP4 had increased resistance to gemcitabine, 5-fluorouracil, and cisplatin, whereas AsPC-1 cells with ZIP4 knockdown had increased sensitivity to these drugs. In mice, xenograft tumors grown from AsPC-1 cells with ZIP4 knockdown were smaller and more sensitive to gemcitabine. ZIP4 overexpression significantly reduced accumulation of gemcitabine in pancreatic cancer cells, increased growth of xenograft tumors in mice, and increased expression of the integrin subunits ITGA3 and ITGB1; expression levels of ITGA3 and ITGB1 were reduced in cells with ZIP4 knockdown. Pancreatic cancer cells with ITGA3 or ITGB1 knockdown had reduced proliferation and formed smaller tumors in mice, despite overexpression of ZIP4; spheroids established from these cells had increased sensitivity to gemcitabine. We found ZIP4 to activate STAT3 to induce expression of ZEB1, which induced expression of ITGA3 and ITGB1 in KPC cells. Increased ITGA3 and ITGB1 expression and subsequent integrin α3ß1 signaling, via c-Jun-N-terminal kinase (JNK), inhibited expression of the gemcitabine transporter ENT1, which reduced gemcitabine uptake by pancreatic cancer cells. ZEB1-knockdown cells had increased sensitivity to gemcitabine. CONCLUSIONS: In studies of pancreatic cancer cell lines and mice, we found that ZIP4 increases expression of the transcription factor ZEB1, which activates expression of ITGA3 and ITGB1. The subsequent increase in integrin α3ß1 signaling, via JNK, inhibits expression of the gemcitabine transporter ENT1, so that cells take up smaller amounts of the drug. Activation of this pathway might help mediate resistance of pancreatic tumors to chemotherapeutic agents.

Cystic Pancreatic Neuroendocrine Tumors Represent a Distinct Clinical Entity with Less Aggressive Biological Behaviors.

BACKGROUND: Pancreatic neuroendocrine tumors (pNETs) uncommonly present as cystic lesions. There is a gap in knowledge of their clinicopathological characteristics and biological behaviors. Previous reported studies remained inconsistent and controversial. The purpose of this study is to investigate the clinicopathological features of cystic pNET and determine if it represents a distinct clinical entity by comparing its characteristics with those of solid pNETs. METHODS: Patients with pNETs who underwent surgical resections from January 2014 to April 2019 at Qilu Hospital of Shandong University were reviewed retrospectively. Demographics, clinical characteristics, surgical data, and oncological as well as histological characteristics of cystic pNETs and their solid counterparts were collected and analyzed. RESULTS: A total of 122 patients were included in this study, and 10.7% (13/122) patients were cystic. There is no significant difference between cystic pNETs and solid pNETs in age (43.6 ± 15.8 versus 50.9 ± 14.5 y, P = 0.093) and sex distribution (P = 0.085). Cystic pNETs are more likely to be asymptomatic (61.5% versus 23.9%, P = 0.008) and nonfunctional (92.3% versus 52.7%, P = 0.006) than solid pNETs. However, the tumor size (4.8 ± 4.5 versus 2.8 ± 1.9 cm, P = 0.124), proportion of multiple endocrine neoplasia type 1 (92.3% versus 98.2%, P = 0.289), and tumor location (P = 0.154) are similar in both groups. Compared with solid pNETs, cystic pNETs have a lower Ki-67 index and incidence of liver metastasis, but the difference is not significant. CONCLUSIONS: Cystic pNETs are more likely to be nonfunctional and indolent and seem to exhibit less aggressive biological behaviors than solid pNETs. Conservative approach should be considered for certain selected patients.

[Progress in diagnosis and treatment of chylous leakage following pancreatic resection].

Compared with other postoperative complications following pancreatic resection, chylous leakage is rare in clinical, which could lead to serious morbidity, including malnutrition,immunosuppression and abdominal infection. The main risk factors for chylous leakage after pancreatic resection are the injury of cisterna chyli or lymphatic vessels caused by intraoperative lymph node dissection and early enteral nutrition. The clinical features of chylous leakage are not specific, and the diagnosis mainly depends on the composition analysis of the drainage fluid. The diagnostic criteria generally adopt the expert consensus of the international Study Group on Pancreatic Surgery,but it is only applicable to isolated chylous leakage and there is still no widely accepted diagnostic criteria in most complex cases. Abdominal fluid analysis and abdominal CT scan are the most applied diagnostic methods for chylous leakage after pancreatic resection,while lymphangiography can not only identify the site of leakage,but also has therapeutic value. For its treatment,the"step-up"treatment strategy is typically applied in most patients. Conservative treatments, including drainage,proper diet and applying octreotide, can benefit most patients. Surgical treatment is not commonly used,and its therapeutic value needs to be further verified. Optimizing perioperative management measures and personalized treatment strategies for different patients can effectively prevent postoperative chylous leakage and maximize the clinical benefits of patients who received pancreatic resection.

Obesity and pancreatic cancer: An update of epidemiological evidence and molecular mechanisms.

Despite advances in therapy and achievements in translational research, pancreatic cancer (PC) remains an invariably fatal malignancy. Risk factors that affect the incidence of PC include diabetes, smoking, obesity, chronic pancreatitis, and diet. The growing worldwide obesity epidemic is associated with an increased risk of the most common cancers, including PC. Chronic inflammation, hormonal effects, circulating adipokines, and adipocyte-mediated inflammatory and immunosuppressive microenvironment are involved in the association of obesity with PC. Herein, we systematically review the epidemiology of PC and the biological mechanisms that may account for this association. Included in this review is a discussion of adipokine-mediated inflammation, lipid metabolism, and the interactions of adipocytes with cancer cells. We consider the influence of bariatric surgery on the risk of PC risk as well as potential molecular targets of therapy. Our review leads us to conclude that targeting adipose tissue to achieve weight loss may represent a new therapeutic strategy for preventing and treating PC.

Cystic pancreatic neuroendocrine tumors: A distinctive subgroup with indolent biological behavior? A systematic review and meta-analysis.

BACKGROUND/OBJECTIVES: The clinicopathological features and biological behaviors of cystic pancreatic neuroendocrine tumors (pNETs) are unclear and controversial. Here we performed a systematic review and meta-analysis to investigate the unique characteristics of cystic pNETs, to determine whether they represent a distinct clinical entity. METHODS: We selected comparative studies published since January 2000 that explore the differences between clinicopathological features of cystic and solid pNETs. Demographic information, pathological characteristics, and survival information were analyzed. RESULT: The 12 selected studies comprised 355 and 1530 patients diagnosed with cystic and solid pNETs, respectively. Compared with solid pNETs, cystic pNETs were less likely to be functional (odds ratio, OR = 0.31, 95% confidence interval (CI) 0.19-0.50, p < 0.00001), more likely to affect males (OR = 1.56, 95% CI 1.22-2.00, p = 0.0005), and significantly associated with multiple endocrine neoplasia type 1 (OR = 2.71). Cystic pNETs were more likely to present with G1 and G2 rather than G3 (OR = 1.66). Cystic pNETs were associated with less frequent distant organs and lymph node metastasis, microvascular invasion, perineural invasion, and a low Ki-67 index and mitotic count. There were no significant differences between 5- and 10-year overall survival. However, the 5-year disease-free survival (DFS) and 10-year DFS rate of patients with cystic pNETs was significantly higher compared with those with solid pNETs (94.6% vs 83.5%, OR = 3.00; 92.7% vs 63.6%, OR = 5.92, respectively). CONCLUSIONS: Cystic pNETs represent a distinct subgroup of pNETs that present with an indolent biological behavior, and patients experience better DFS. Observation and surveillance should be considered in some selected cases.

Correlation between laparoscopic transection of an indirect inguinal hernial sac and postoperative seroma formation: a prospective randomized controlled study.

BACKGROUND: Seroma is the most common early minor complication of inguinal hernia repair. Seromas generally resolve spontaneously within a few weeks, but can sometimes cause other complications. The optimal ways to repair inguinal hernia and handle the hernial sac are still debatable. Large scale, prospective, randomized, controlled studies focusing on the correlation between transection of the hernial sac and seroma formation are scarce. METHODS: A total of 159 adult male patients with primary indirect inguinal hernia who underwent laparoscopic transabdominal preperitoneal repair were recruited. The patients were randomized to undergo either complete dissection or transection of the hernial sacs. Patients were followed up at postoperative 7 days, 1 and 3 months, looking specifically for seroma. Seroma was diagnosed via physical examination, and a prestructured form was used to evaluate patient recovery and define the type of seroma present at each follow-up visit. RESULTS: There were 83 patients in the completely dissected group and 76 in the transected group. The overall incidence of postoperative seroma was 12.6% (n = 20). The χ2 test demonstrated that significantly more patients developed seroma in the transected group than in the completely dissected group (18.4% vs. 7.2%, p = 0.034); there were also significant differences between the two groups in the incidences of seroma at postoperative 7 days (18.4% vs. 6.0%, p = 0.016) and 1 month (14.5% vs. 4.8%, p = 0.037). Seroma formation was correlated with age, body mass index, use of anticoagulants, hernia type, hernia size, sac size, and operative time. There were no significant differences between the two groups in the degree of postoperative pain and time taken for the resumption of outdoor activities. CONCLUSIONS: When using the laparoscopic transabdominal preperitoneal technique for indirect inguinal hernia repair, the risk of postoperative seroma formation is greater after transection compared with complete dissection of the hernial sac.

Early detection of pancreatic cancer: Where are we now and where are we going?

Pancreatic cancer (PC) is one of the most lethal malignancies. Recent studies indicate that patients with incidentally diagnosed PC have better prognosis than those with symptoms and that there is a sufficient window for early detection. However, effective early diagnosis remains difficult and depends mainly on imaging modalities and the development of screening methodologies with highly sensitive and specific biomarkers. This review summarizes recent advances in effective screening for early diagnosis of PC using imaging modalities and novel molecular biomarkers discovered from various "omics" studies including genomics, epigenomics, non-coding RNA, metabonomics, liquid biopsy (CTC, ctDNA and exosomes) and microbiomes, and their use in body fluids (feces, urine and saliva). Although many biomarkers for early detection of PC have been discovered through various methods, larger scale and rigorous validation is required before their application in the clinic. In addition, more effective and specific biomarkers of PC are urgently needed.

MicroRNA-195 Suppresses the Progression of Pancreatic Cancer by Targeting DCLK1.

BACKGROUND/AIMS: Doublecortin-like kinase 1 (DCLK1) is emerging as a tumor-specific stem cell marker in pancreatic cancer (PC). MicroRNA-195 (miR-195) plays an important role in many types of tumors. However, the roles of DCLK1 in cancer and miRNAs that directly regulate DCLK1 have not been elucidated. The goal of this study is to assess the effects of miR-195 on inhibiting DCLK1 and to clarify the regulating mechanism of miR-195-DCLK1 in PC cells. METHODS: The expression of DCLK1 protein and miR-195 in PC tissues and adjacent healthy pancreatic tissues was detected by Western blot and quantitative reverse transcription polymerase chain reaction (qRT-PCR), respectively and the correlation between overall survival of PC patients and expression of DCLK1 was measured by Kaplan-Meier analysis. Bioinformatics tools were used to identify the target gene of miR-195. Effects of miR-195 and DCLK1 on proliferation and cell cycle of PC cells were analyzed by MTT, colony formation assays and flow cytometry. Transwell and wound-healing experiments were employed to examine the cellular migration and invasion. A xenograft mouse model was also used to test the effects of miR-195 on tumor growth and metastasis in vivo. RESULTS: The expression level of DCLK1 and miR-195 shows an inverse correlation in PC tissues and cell lines. A higher DCLK1 level is associated with higher TNM (tumor, node, and metastasis) stage, higher rate of lymph node metastasis, and poor survival. Luciferase reporter assay shows that miR-195 directly targets DCLK1. Overexpression of miR-195 inhibits proliferation, migration and invasion of PC cells, whereas downregulation of miR-195 has an opposite role. These actions were similar to the effects of knockdown and overexpression of DCLK1, respectively. CONCLUSIONS: These data suggest that miR-195 has tumor suppressor roles in PC by targeting DCLK1. MiR-195-DCLK1 pathway may provide insight into PC progression and represent a novel, promising diagnostic and therapeutic target for PC.

Partial Splenectomy is Superior to Total Splenectomy for Selected Patients with Hemangiomas or Cysts.

BACKGROUND: The superiority of partial splenectomy (PS) as a treatment for benign tumors has not well been confirmed. This study aimed to identify the short- and long-term outcomes of PS, to compare laparoscopic and laparotomic PS, and to demonstrate whether the effects of PS are superior to that of total splenectomy (TS). METHODS: Patients with either a hemangioma or cyst who underwent PS or TS from 2009 to 2015 at Qilu Hospital of Shandong University were included. Clinical parameters were collected and analyzed. RESULTS: A total of 17 patients underwent PS were collected, including 2 men and 15 women with a mean age of 43.9 ± 11.3 years old. Patients who underwent laparoscopic PS (9 cases) had a longer operative time and shorter postoperative hospital stay than those who underwent laparotomy (8 cases). Compared with TS (22 cases), PS significantly decreased the incidence of thrombocytosis, shortened time until drainage removal, and shortened postoperative hospital stay. After an average follow-up of 34.8 months, patients who underwent TS showed a higher incidence of thrombocytosis and splenic vein thrombosis compared with patients underwent PS. CONCLUSIONS: PS is technically feasible and provides favorable short- and long-term outcomes for selected patients with either a hemangioma or cyst compared with TS. Laparoscopic PS shows lower morbidity and equal therapeutic efficacy compared with laparotomic PS and can be widely performed.

Vacuum suction fixation versus staple fixation in TAPP laparoscopic hernia repair: introduction of a new technique for mesh fixation.

BACKGROUND: Proper mesh fixation is critical for successful TAPP laparoscopic hernia repair. Conventional mesh fixation may cause chronic neuralgia, groin paresthesia or other complications. This study aimed at introducing a new vacuum suction technique for mesh fixation and evaluating its efficacy and safety compared with traditional staple fixation way. METHODS: Clinical data of 242 patients undergoing TAPP from July 2011 to March 2014 were retrospectively analyzed. Patients were divided into vacuum suction fixation group and staple fixation group. The operation time, hospital stay, complications, recurrence, visual analogue scale pain score and cost were evaluated. RESULTS: All surgeries were successful. The operation time of staple group was (42.34 ± 10.15) min for unilateral hernia and (64.08 ± 16.01) min for bilateral hernias. The postoperative hospital stay was (2.76 ± 0.84) days. One recurrence was observed (0.90%). For vacuum group, the operation time was (42.66 ± 7.76) min and (63.92 ± 10.49) min, and hospital stay was (2.60 ± 0.74) days. No recurrence was observed. There was no significant difference in recurrence, operation time, postoperative pain and hospital stay between two groups (P > 0.05). Average cost were (11,714 ± 726) RMB for vacuum group which was lower than staple group (14,837 ± 1568) RMB (P < 0.05). The top three complications of staple group were scrotal emphysema (10.81%), scrotal seroma (6.31%) and temporary nerve paresthesia (4.50%) while for vacuum group, they were scrotal seroma (3.82%), temporary nerve paresthesia (3.05%), scrotal emphysema (1.53%) and uroschesis (1.53%). The incidence of scrotal emphysema was lower in vacuum group (P < 0.05). No significant difference was observed in other complications (P > 0.05). CONCLUSION: Both techniques for mesh fixation are safe and effective. There is no significant difference in recurrence, operation time, postoperative pain or hospital stay. The vacuum suction fixation technique is more economical with lower incidence of scrotal emphysema.

Lymph node ratio is an independent prognostic factor for patients after resection of pancreatic cancer.

BACKGROUND: The prognostic value of lymph node ratio (LNR) in pancreatic cancer remains controversial. In the current retrospective study, we assessed the value of LNR on predicting the survival of postoperative patients with pancreatic cancer. METHODS: Medical records of patients who underwent pancreatic resection for pancreatic cancer in the department of general surgery, Qilu Hospital, Shandong University were reviewed retrospectively. Demographic, clinicopathological, tumor-specific data, and histopathological reports were collected. Univariate and multivariate survival analyses were performed. RESULTS: A total of 83 patients with pancreatic cancer were collected. The mean number of examined LN was 8.2 ± 6.1 (0 to 26). Differential degree (low) (P = 0.019, hazard ratio (HR) = 2.276, 95% confidence interval (CI): 1.171 to 4.424) and LNR >0.2 (P = 0.018, HR = 2.685, 95% CI: 1.253 to 5.756) were independent adverse prognostic factors according to the multivariate survival analysis. CONCLUSIONS: Our study indicated that LNR >0.2 was an independent adverse prognostic factor for pancreatic cancer, which may provide important information for prognostic assessment.

[The effects of sleeve gastrectomy on renal function in type 2 diabetic rats].

OBJECTIVE: To examine the renal function changes and mechanisms on rats with diabetes through a sleeve gastrectomy operation. METHODS: Thirty-six rats were induced diabetes through injection of streptozotocin (STZ), and 30 of these diabetic rats that blood glucose levels at the midrange (blood sugar 17.88-23.65 mmol/L, mean: 20.32 mmol/L) were randomly assigned to the sleeve gastrectomy group, Sham-operation group and control group. The serum creatinine, lipid parameters were measured postoperatively. The 24 h urine volume obtained and urine albumin excretion rate (UAER) was calculated. Serum and urinary creatinine were examined and glomerular filtration rate (GFR) was counted. Kidney sections were stained with periodic acid-Schiff, and then the index of mesangial expansion was determined. The expression of synaptopodin for podocytes was also performed through the immunohistochemical procedure. A one-way ANOVA and t-test were performed to evaluate differences between groups and each other. RESULTS: Only one rat of SG group died after operation. The GFR ((8.44 ± 2.10) ml · g⁻¹ · d⁻¹), 24 h UAER ((36.04 ± 11.10) mg/d), plasma lipids level (total cholesterol (1.66 ± 0.23) mmol/L, triglycerides (1.25 ± 0.17) mmol/L), kidney weight ((1.61 ± 0.06) g), the index of mesangial expansion ((6.14 ± 1.50)%) and synaptopodin expression ((20.44 ± 2.99)%) were improved in the SG group compared with the sham-operation group ((15.05 ± 3.01) ml · g⁻¹ · d⁻¹, (57.01 ± 11.34) mg/d, (2.15 ± 0.29) mmol/L, (1.65 ± 0.23) mmol/L, (1.93 ± 0.07) g, (11.32 ± 2.09)%, (10.34 ± 1.43)%) and control group ((14.79 ± 2.38) ml · g⁻¹ · d⁻¹, (62.71 ± 16.46) mg/d, (2.23 ± 0.21) mmol/L, (1.59 ± 0.20) mmol/L, (1.91 ± 0.06) g, (10.82 ± 1.79)%, (11.13 ± 2.43)%) (t = 0.781-5.025, all P < 0.05). CONCLUSION: The sleeve gastrectomy procedure can improve the renal function in a diabetes rat model may be through protecting the podocytes function and preventing the mesangial expansion of glomeruli.

Immune reactions following intestinal transplantation: Mechanisms and prevention.

For patients with intestinal failure, small bowel transplantation remains one of the most effective treatments despite continuous advancements in parenteral nutrition techniques. Long-term use of parenteral nutrition can result in serious complications that lead to metabolic dysfunction and organ failure. However, the small intestine is a highly immunogenic organ with a large amount of mucosa-associated lymphoid tissue and histocompatibility antigens; therefore, the small intestine is highly susceptible to severe immune rejection. This article discusses the mechanisms underlying immune rejection after small bowel transplantation and presents various options for prevention and treatment. Our findings offer new insights into the development of small bowel transplantation.

Regulation of newly identified lysine lactylation in cancer.

Metabolic reprogramming is a typical hallmark of cancer. Enhanced glycolysis in tumor cells leads to the accumulation of lactate, which is traditionally considered metabolic waste. With the development of high-resolution liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS), the lactate-derived, lysine lactylation(Kla), has been identified. Kla can alter the spatial configuration of chromatin and regulate the expression of corresponding genes. Metabolic reprogramming and epigenetic remodeling have been extensively linked. Accumulating studies have subsequently expanded the framework on the key roles of this protein translational modification (PTM) in tumors and have provided a new concept of cancer-specific regulation by Kla.