Research progress on microRNAs as molecular markers in pancreatic cancer: a narrative review.

Background and Objective: The incidence and mortality of pancreatic cancer (PC) have increased in recent years. The current status of PC diagnosis and treatment remains grim in clinical practice because the commonly used early screening tools are not sufficient. Improving the early detection of PC and strengthening standardized comprehensive treatment remain the focus of PC research. Many studies have shown that micro RNAs (miRNAs) play an important role in the occurrence, development, and treatment of PC. It is expected that miRNAs will become new molecular markers of PC. Methods: We extracted and compiled useful information from the PubMed database that met our criteria for analyzing PC diagnosis, treatment, and prognosis. Key Content and Findings: In this narrative review, we summarize the mechanism of some miRNAs in the occurrence and development of PC and review them as potential markers for the diagnosis, treatment, and prognosis of PC. The function of miRNAs in PC has great potential in studying the pathogenesis of PC. The discovery of many important oncogenic miRNAs and their downstream targets will bring new ideas and research paths for the diagnosis and targeted therapy of PC. Conclusions: MiRNAs are expected to provide novel ideas and research directions for the diagnosis and targeted treatment of PC. However, more patient data and clinical trials are needed before miRNAs can become novel molecular markers for PC.

Application of artificial intelligence to pancreatic adenocarcinoma.

Background and Objectives: Pancreatic cancer (PC) is one of the deadliest cancers worldwide although substantial advancement has been made in its comprehensive treatment. The development of artificial intelligence (AI) technology has allowed its clinical applications to expand remarkably in recent years. Diverse methods and algorithms are employed by AI to extrapolate new data from clinical records to aid in the treatment of PC. In this review, we will summarize AI's use in several aspects of PC diagnosis and therapy, as well as its limits and potential future research avenues. Methods: We examine the most recent research on the use of AI in PC. The articles are categorized and examined according to the medical task of their algorithm. Two search engines, PubMed and Google Scholar, were used to screen the articles. Results: Overall, 66 papers published in 2001 and after were selected. Of the four medical tasks (risk assessment, diagnosis, treatment, and prognosis prediction), diagnosis was the most frequently researched, and retrospective single-center studies were the most prevalent. We found that the different medical tasks and algorithms included in the reviewed studies caused the performance of their models to vary greatly. Deep learning algorithms, on the other hand, produced excellent results in all of the subdivisions studied. Conclusions: AI is a promising tool for helping PC patients and may contribute to improved patient outcomes. The integration of humans and AI in clinical medicine is still in its infancy and requires the in-depth cooperation of multidisciplinary personnel.

MiR-520a-5p/PPP5C regulation pattern is identified as the key to gemcitabine resistance in pancreatic cancer.

Objective: To explore the effects of the expression level of miR-520-5p/PPP5C in pancreatic cancer cells and exosomes on cell viability, angiogenesis, autophagy, which involved in the mechanism of gemcitabine resistance in pancreatic cancer. Methods: APSC-1 cell line was treated with gemcitabine, after which its exosomes were extracted for NTA assay. Subsequently, the drug resistance of APSC-1 cells was assayed using CCK8, as well as the activity of HUVEC cells treated with exosomes from each group of APSC-1 cells after drug resistance treatment as well as overexpression treatment. Five groups of HUVEC cells treated with exosomes were subjected to in vitro tubule formation assay. levels of PPP5C in each group of ASPC-1 cells and their exosomes, levels of overexpressed PPP5C, and related exosomal proteins were examined by WB. mRNA expression levels of PPP5C and levels of miR-520a were examined by qPCR The relationship between miR-520a-5p and PPP5C was investigated. After that, the autophagy of PPP5C was detected. Finally, it was analyzed by TCGA database for survival prognosis analysis. Results: APSC-1 cells had an IC50 value of 227.1 µM for gemcitabine, elevated PPP5C expression, drug resistance, and enhanced HUVEC cell activity; exosomes CD9, CD63, and CD81 were significantly expressed in all groups; meanwhile, enhanced PPP5C expression not only promoted in vitro tubule formation but also increased autophagy levels; meanwhile, its relationship with miR-520-5p and There was a targeted inhibitory relationship between its level and miR-520-5p and PPP5C, and its elevated level also led to a decrease in the survival level of patients over 3-5 years. Conclusion: PPP5C has a prognostic role in pancreatic cancer by promoting the value-added and invasion of pancreatic cancer cells, and a targeted inhibitory relationship between miR-520-5p and PPP5C was found.

Lactate promotes the growth of patient-derived organoids from hepatopancreatobiliary cancers via ENO1/HIF1α pathway and does not affect their drug sensitivities.

The long culture duration of patient-derived organoids (PDOs) have severely limited their clinical applications. The aim of this study was to determine the effect of lactate supplementation on the growth, genetic profiles and drug sensitivities of PDOs from hepatopancreatobiliary tumors. LM3, Huh7, Panc02, and RBE cell lines were cultured as organoids in the presence or absence of lactate, and total protein was extracted to measure the expression of α-enolase (ENO1), hypoxia-inducible factor-1α (HIF1α), AKT, and PI3 kinase (PI3K). Thirteen hepatopancreatobiliary tumor specimens were collected during surgical resection and cultured as PDOs with or without L-lactate. Hematoxylin and eosin (H&E) staining and immunohistochemical staining were performed on the original tissues and PDOs to compare their pathological structures, and their genetic profiles were analyzed by whole-exome sequencing (WES). The sensitivity of the PDOs to gemcitabine, 5-fluorouracil, cisplatin, paclitaxel, ivosidenib, infigratinib, and lenvatinib were evaluated in terms of cell viability. Peripheral blood mononuclear cells (PBMCs) were isolated and co-cultured with PDOs to test the sensitivity of PDOs to tislelizumab. The addition of 20 mM lactate significantly promoted the growth of LM3 and Huh 7 organoids by 217% and 36%, respectively, compared to the control group, and the inhibition of lactate transporter decreased their growth. The HIF1α/ENO1/AKT/PI3K pathway was also activated by lactate. The inhibition of enolase also partly decreased the growth of organoids treated with lactate. Furthermore, 20 mM lactate increased the viability of 9 PDOs from 135% to 317% without affecting their pathological features. The genetic similarity, in terms of single nucleotide variations, insertions, and deletions, between original tissues and lactate-treated PDOs ranged from 83.2% to 94.1%, and that between the untreated and lactate-treated PDOs was at least 93.2%. Furthermore, the addition of lactate did not significantly change the dose-response curves of the PDOs to chemotherapeutic drugs, targeted drugs, and immune checkpoint inhibitor, especially for the drugs to which the cells were sensitive. Thus, lactate can be added to the culture medium of PDOs to promote their growth without altering their genetic profiles and drug sensitivities.

The Key Genes for Perineural Invasion in Pancreatic Ductal Adenocarcinoma Identified With Monte-Carlo Feature Selection Method.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is the most aggressive form of pancreatic cancer. Its 5-year survival rate is only 3-5%. Perineural invasion (PNI) is a process of cancer cells invading the surrounding nerves and perineural spaces. It is considered to be associated with the poor prognosis of PDAC. About 90% of pancreatic cancer patients have PNI. The high incidence of PNI in pancreatic cancer limits radical resection and promotes local recurrence, which negatively affects life quality and survival time of the patients with pancreatic cancer. OBJECTIVES: To investigate the mechanism of PNI in pancreatic cancer, we analyzed the gene expression profiles of tumors and adjacent tissues from 50 PDAC patients which included 28 patients with perineural invasion and 22 patients without perineural invasion. METHOD: Using Monte-Carlo feature selection and Incremental Feature Selection (IFS) method, we identified 26 key features within which 15 features were from tumor tissues and 11 features were from adjacent tissues. RESULTS: Our results suggested that not only the tumor tissue, but also the adjacent tissue, was informative for perineural invasion prediction. The SVM classifier based on these 26 key features can predict perineural invasion accurately, with a high accuracy of 0.94 evaluated with leave-one-out cross validation (LOOCV). CONCLUSION: The in-depth biological analysis of key feature genes, such as TNFRSF14, XPO1, and ATF3, shed light on the understanding of perineural invasion in pancreatic ductal adenocarcinoma.

The Serum MicroRNA Signatures for Pancreatic Cancer Detection and Operability Evaluation.

Pancreatic cancer (PC) has high morbidity and mortality. It is the fourth leading cause of cancer death. Its diagnosis and treatment are difficult. Liquid biopsy makes early diagnosis of pancreatic cancer possible. We analyzed the expression profiles of 2,555 serum miRNAs in 100 pancreatic cancer patients and 150 healthy controls. With advanced feature selection methods, we identified 13 pancreatic cancer signature miRNAs that can classify the pancreatic cancer patients and healthy controls. For pancreatic cancer treatment, operation is still the first choice. But many pancreatic cancer patients are already inoperable. Therefore, we compared the 79 inoperable and 21 operable patients and identified 432 miRNAs that can predict whether a pancreatic cancer patient was operable. The functional analysis of the 13 pancreatic cancer signatures and the 432 operability miRNAs revealed the molecular mechanisms of pancreatic cancer and shield light on the diagnosis and therapy of pancreatic cancer in clinical practice.

Laparoscopy Versus Open Reoperation for Incidental Gallbladder Carcinoma After Laparoscopic Cholecystectomy.

Background: Some reports assert that there is a risk that laparoscopy might worsen the prognosis of incidental gallbladder carcinoma (IGBC) after laparoscopic cholecystectomy (LC) compared with open reoperation. The purpose of this study was to evaluate whether the surgical approach influences outcomes in patients with IGBC after LC. Methods: We retrospectively reviewed the medical records of 106 patients diagnosed with IGBC who had undergone LC for benign gallbladder disease such as cholecystolithiasis at our hospital between April 2010 and February 2018. We included patients with incidentally diagnosed GBC after routine pathology: 45 patients (16 men and 29 women; age: 45-76 years [mean: 62.6 years]) who underwent laparoscopic surgery and 61 patients (24 men and 37 women; age: 51-82 years [mean: 62.6 years]) who underwent open surgery. We evaluated outcomes in each group regarding tumor stage and operative time, time of reoperation after first operation, blood loss volume, number of lymph nodes in pathological specimens, hospital stay, and complication and survival rates. Results: Reoperation time after first operation, number of lymph nodes in pathological specimens, and operative time showed no statistical significance between laparoscopy and open reoperation. During follow-up, 3-year survival between laparoscopy (48.89%) and open reoperation (42.62%) showed no statistical significance, but laparoscopy had better 1-year survival (95.56% versus 86.89%, laparoscopy versus open, respectively; not significant [NS] <0.01) and 5-year survival (44.44% versus 29.51%, laparoscopy versus open, respectively; NS <0.05). However, comparing laparoscopy versus open surgery, respectively, blood -loss volume (100 ± 25.4 mL versus 200 ± 45.6 mL; NS <0.01), hospital stay (3.5 ± 1.9 days versus 5.6 ± 2.7 days, NS <0.01), and complication rates (6.7% versus 13.1%; NS <0.01) were lower, indicating better recovery and better patient experience. Conclusions: Laparoscopic radical reoperation for IGBC after LC is a feasible, effective, and safe procedure and is associated with less bleeding, low morbidity, and shorter hospital stay.

MiR-139-5p/SLC7A11 inhibits the proliferation, invasion and metastasis of pancreatic carcinoma via PI3K/Akt signaling pathway.

OBJECTIVE: Pancreatic carcinoma (PANC) is one of the important aggressive cancers, with deficiency in effective therapeutics. The study aimed to investigate the effects and molecular mechanism of miR-139-5p/SLC7A11 on the proliferation and metastasis of PANC. METHODS: Bioinformatics was used to analyze the differentially expressed genes in the TCGA database. PANC cell lines with overexpressed miR-139-5p and Solute Carrier Family 7, Member 11 (SLC7A11) was established, and have been used to detect cell proliferation, invasion and metastasis of PANC Subsequently, bioinformatic analysis and dual luciferase reporter assay were performed to confirm that SLC7A11 was a target gene of miR-139-5p. Xenograft mice model was used to explore the functions of miR-139-5p in PANC tumorigenicity. RESULTS: MiR-139-5p could regulate and affect the protein expression of P13K and Akt associated with phosphatidylinositol signaling pathway by inhibiting SLC7A11. MiR-139-5p was found to be lowly expressed in PANC tissues, while SLC7A11 was highly expressed. Low expression of miR-139-5p and high expression of SLC7A11 were positively associated with poor clinical outcomes. PANC cell proliferation, invasion and metastasis could be inhibited by miR-139-5p overexpression and be promoted by SLC7A11 overexpression. MiR-139-5p overexpression could suppress PANC tumor growth and the expressions of SLC7A11, p-PI3K, p-Akt in tumor tissues. Therefore, the inhibitory of miR-139-5p to PANC cell proliferation, invasion and metastasis was partly due to its inhibiting effect on SLC7A11 expression. CONCLUSION: Our study proves that miR-139-5p/SLC7A11 has important functions on PANC, suggesting that miR-139-5p can be used as a biomarker for PANC patients.

Autologous Blood Transfusion and Pringle Maneuver in Laparoscopic Segmental Hepatectomy for Benign Hepatic Neoplasms: A Retrospective Study.

Objectives: To investigate the effect of autologous blood transfusion (ABT) and Pringle maneuver (PM) on postoperative early liver function and short-term postoperative results following laparoscopic liver resection in patients with benign hepatic neoplasms. Materials and Methods: We retrospectively analyzed the clinical data for 125 consecutive patients who underwent laparoscopic segmental hepatectomy from January 2015 to May 2018 (68 in the ABT group versus 57 in the PM group). We compared patients' characteristics and intra- and postoperative short-term outcomes between the groups. Results: The 2 groups were well matched regarding patients' clinical characteristics, types of liver resection, operative time, and histopathological findings (P > .05). Median blood loss was significantly lower in the PM group versus the ABT group (200 mL versus 750 mL, respectively; P < .01), and overall complication rates were similar (n = 12 [17%] versus n = 9 [16%], respectively; P > .05). The ABT group had significantly lower mean levels of total bilirubin, indirect bilirubin, aspartate transaminase, and alanine aminotransferase on postoperative days 1 and 3 (P < .05). The ABT group had a shorter hospital stay compared with the PM group (5.8 days versus 7.7 days, respectively; P < .05) and lower hospitalization costs (55,400 ± 15,400 versus 667,000 ± 21,600 CN dollars, respectively; P < .05). Conclusions: Compared with Pringle's maneuver, laparoscopic hepatectomy with ABT promoted early recovery of liver function and reduced hospitalization costs in select patients with benign hepatic neoplasms.

Fast-track care with intraoperative blood salvage in laparoscopic splenectomy.

Fast-track surgery is claimed to reduce medical morbidity, eliminate the hospitalization needs, and shorten the convalescence period. Intraoperative bleeding as the main complication is also the primary cause of conversion from laparoscopic to open splenectomy. Intraoperative blood salvage can reduce transfusion requirements, decrease the conversion rate to open, and promote fast-tracking in laparoscopic splenectomy (LS). From November 2007 through December 2016 we collected medical data of 115 LS patients. There were three groups: 54 patients receiving routine care (we marks them as Group RT), 33 patients with fast-track care (Group FT), and 28 receiving fast-track care receiving intraoperative splenic blood salvage and autotransfusion (Group FT + ISBS). These medical data are comprised of included three phases (pre-, intra-, and postoperative). There were significant differences (P < 0.05) between RT, FT, and FT + ISBS groups. The hemoglobin level in Group FT + ISBS was significantly higher than in Group RT and Group FT. Comparing the duration of hospital stay of 3 groups, Group RT stayed for a significantly longer time than Group FT and Group FT + ISBS, Group FT + ISBSmuch shorter than Group FT. Comparing the hospitalization expense, GroupFT + ISBS significantly expended less than Group RT and Group FT. Our study shows that laparoscopic splenectomy with fast-track care is feasible, effective, and safe for patients who require splenectomy. Fast-tracking with intraoperative blood salvage improved the fast-track laparoscopic splenectomy procedure.

Laparoscopic Repair of Diaphragmatic Eventeration in Adults: Plication With Mesh Repair.

BACKGROUND: Diaphragmatic eventeration is a rare congenital anomaly consisting of defect of diaphragm muscular development, which can be diagnosed with chest radiography and clinical evaluation. Diaphragmatic plication is a well-established treatment for diaphragmatic eventeration, which can be done through the thoracic or abdominal route, and minimally invasive became the trend in recent years. METHODS: The study retrospectively analyzed 3 cases of diaphragmatic eventeration with the procedure of laparoscopic diaphragmatic plication with mesh repair from August 2016 to April 2017. A detailed review of medical records and the perioperative data including patient characteristics, operative details, and postoperative hospital stay was conducted. RESULTS: Laparoscopic diaphragmatic plication with mesh repair for diaphragmatic eventeration was successfully completed for 3 patients. The mean operation time was 125 minutes (range, 120 to 135 min), and the mean blood loss was 13.3 mL (range, 10 to 15 mL). The postoperative intercostal neuralgia was detailed evaluated and intervention as necessary. All patients were followed up at 1, 3, and 6 months after procedure, and the recoveries were uneventful. CONCLUSIONS: Laparoscopic diaphragmatic plication with mesh repair provides a new operative view, which may be a safe and feasible alternative in the surgical management of diaphragmatic eventeration.

Combined laparoscopic and open technique for repair of congenital abdominal hernia: A case report of prune belly syndrome.

BACKGROUND: Prune belly syndrome (PBS) is a rare congenital disorder among adults, and the way for repairing abdominal wall musculature has no unified standard. MATERIALS AND METHODS: We described combining laparoscopic and open technique in an adult male who presented with PBS. Physical examination and radiological imaging verified the case of PBS. The deficiency of abdominal wall musculature was repaired by combining laparoscopic and open technique using a double-deck complex patch. RESULTS: The patient successfully underwent abdominal wall repair by combining laparoscopic and open technique. Postoperative recovery was uneventful, and improvement in symptom was significant in follow-up after 3, 6, 12, and 24 months. CONCLUSIONS: Combining laparoscopic and open technique for repair of deficiency of abdominal wall musculature in PBS was an exploratory way to improve life quality.

Comparison of Laparoscopic Sleeve Gastrectomy and Laparoscopic Greater Curvature Plication Regarding Efficacy and Safety: a Meta-Analysis.

Laparoscopic sleeve gastrectomy (LSG) and laparoscopic greater curvature plication (LGCP) are two restrictive bariatric procedures. Eight studies (three randomized, controlled trials, four retrospective studies, and one prospective study) with 536 patients on LSG and LGCP were included by searching PUBMED, EMBASE, and the Cochrane Library. The software Review Manager 5.3 was used to evaluate operation time, adverse events, percent excess weight loss (%EWL), resolution of obesity-related comorbidities, and postoperative hospital stay. Despite the limitations, this meta-analysis suggests that LSG is superior to LGCP in terms of providing greater %EWL at the follow-up of 3, 6, and 12 months and 3 years. LSG gains shorter postoperative hospital stay than LGCP. No significant difference was found in operation time, adverse events, and the resolution of obesity-related comorbidities.

The Superior Inguinal Ligament Approach of Single Incision Laparoscopic Surgery for Total Extraperitoneal Inguinal Hernia Repair.

BACKGROUND: Total extraperitoneal (TEP) inguinal hernia repair gained popularity in the past two decades for its advantage, especially single incision laparoscopic surgery (SILS) for TEP inguinal hernia repair (SILS TEP), however, which is a technically demanding procedure. METHODS: The study retrospectively analyzed 6 cases of the superior of inguinal ligament approach of S-SILS TEP repair from August 2015 to July 2016. A detailed review of medical records and the perioperative data including patient characteristics, operative details, and postoperative hospital stay was conducted. RESULTS: S-SILS TEP repair for inguinal hernia was successfully completed for 6 patients, and the mean operation time was 59.2 minutes (range 55-70 minutes), and the mean blood loss was 7.5 mL (range 5-15 mL) and the postoperative recovery was uneventful about 3 days after operation with a single wound over inguinal ligament. CONCLUSIONS: S-SILS TEP repair provides a new operative view, which combines the advantage of laparoscopic and open surgery, especially in surgical technique and minimal invasiveness. Our experience suggests that the S-SILS TEP repair may be a safe and feasible alternative in inguinal hernias repair.