DNA hypomethylation patterns and their impact on the tumor microenvironment in colorectal cancer.

BACKGROUND: Recent research underscores the pivotal role of immune checkpoints as biomarkers in colorectal cancer (CRC) therapy, highlighting the dynamics of resistance and response to immune checkpoint inhibitors. The impact of epigenetic alterations in CRC, particularly in relation to immune therapy resistance, is not fully understood. METHODS: We integrated a comprehensive dataset encompassing TCGA-COAD, TCGA-READ, and multiple GEO series (GSE14333, GSE37892, GSE41258), along with key epigenetic datasets (TCGA-COAD, TCGA-READ, GSE77718). Hierarchical clustering, based on Euclidean distance and Ward's method, was applied to 330 primary tumor samples to identify distinct clusters. The immune microenvironment was assessed using MCPcounter. Machine learning algorithms were employed to predict DNA methylation patterns and their functional enrichment, in addition to transcriptome expression analysis. Genomic mutation profiles and treatment response assessments were also conducted. RESULTS: Our analysis delineated a specific tumor cluster with CpG Island (CGI) methylation, termed the Demethylated Phenotype (DMP). DMP was associated with metabolic pathways such as oxidative phosphorylation, implicating increased ATP production efficiency in mitochondria, which contributes to tumor aggressiveness. Furthermore, DMP showed activation of the Myc target pathway, known for tumor immune suppression, and exhibited downregulation in key immune-related pathways, suggesting a tumor microenvironment characterized by diminished immunity and increased fibroblast infiltration. Six potential therapeutic agents-lapatinib, RDEA119, WH.4.023, MG.132, PD.0325901, and AZ628-were identified as effective for the DMP subtype. CONCLUSION: This study unveils a novel epigenetic phenotype in CRC linked to resistance against immune checkpoint inhibitors, presenting a significant step toward personalized medicine by suggesting epigenetic classifications as a means to identify ideal candidates for immunotherapy in CRC. Our findings also highlight potential therapeutic agents for the DMP subtype, offering new avenues for tailored CRC treatment strategies.

Robotic Versus Laparoscopic Liver Resection in Various Settings: An International Multicenter Propensity Score Matched Study of 10.075 Patients.

OBJECTIVE: To compare the perioperative outcomes of robotic liver surgery (RLS) and laparoscopic liver surgery (LLS) in various settings. BACKGROUND: Clear advantages of RLS over LLS have rarely been demonstrated, and the associated costs of robotic surgery are generally higher than those of laparoscopic surgery. Therefore, the exact role of the robotic approach in minimally invasive liver surgery remains to be defined. METHODS: In this international retrospective cohort study, the outcomes of patients who underwent RLS and LLS for all indications between 2009 and 2021 in 34 hepatobiliary referral centers were compared. Subgroup analyses were performed to compare both approaches across several types of procedures: (1) minor resections in the anterolateral (2, 3, 4b, 5, and 6) or (2) posterosuperior segments (1, 4a, 7, 8), and (3) major resections (≥3 contiguous segments). Propensity score matching was used to mitigate the influence of selection bias. The primary outcome was textbook outcome in liver surgery (TOLS), previously defined as the absence of intraoperative incidents ≥grade 2, postoperative bile leak ≥grade B, severe morbidity, readmission, and 90-day or in-hospital mortality with the presence of an R0 resection margin in case of malignancy. The absence of a prolonged length of stay was added to define TOLS+. RESULTS: Among the 10.075 included patients, 1.507 underwent RLS and 8.568 LLS. After propensity score matching, both groups constituted 1.505 patients. RLS was associated with higher rates of TOLS (78.3% vs 71.8%, P < 0.001) and TOLS+ (55% vs 50.4%, P = 0.026), less Pringle usage (39.1% vs 47.1%, P < 0.001), blood loss (100 vs 200 milliliters, P < 0.001), transfusions (4.9% vs 7.9%, P = 0.003), conversions (2.7% vs 8.8%, P < 0.001), overall morbidity (19.3% vs 25.7%, P < 0.001), and microscopically irradical resection margins (10.1% vs. 13.8%, P = 0.015), and shorter operative times (190 vs 210 minutes, P = 0.015). In the subgroups, RLS tended to have higher TOLS rates, compared with LLS, for minor resections in the posterosuperior segments (n = 431 per group, 75.9% vs 71.2%, P = 0.184) and major resections (n = 321 per group, 72.9% vs 67.5%, P = 0.086), although these differences did not reach statistical significance. CONCLUSIONS: While both produce excellent outcomes, RLS might facilitate slightly higher TOLS rates than LLS.

International consensus guidelines on robotic pancreatic surgery in 2023.

Background: With the rapid development of robotic surgery, especially for the abdominal surgery, robotic pancreatic surgery (RPS) has been applied increasingly around the world. However, evidence-based guidelines regarding its application, safety, and efficacy are still lacking. To harvest robust evidence and comprehensive clinical practice, this study aims to develop international guidelines on the use of RPS. Methods: World Health Organization (WHO) Handbook for Guideline Development, GRADE Grid method, Delphi vote, and the AGREE-II instrument were used to establish the Guideline Steering Group, Guideline Development Group, and Guideline Secretary Group, formulate 19 clinical questions, develop the recommendations, and draft the guidelines. Three online meetings were held on 04/12/2020, 30/11/2021, and 25/01/2022 to vote on the recommendations and get advice and suggestions from all involved experts. All the experts focusing on minimally invasive surgery from America, Europe and Oceania made great contributions to this consensus guideline. Results: After a systematic literature review 176 studies were included, 19 questions were addressed and 14 recommendations were developed through the expert assessment and comprehensive judgment of the quality and credibility of the evidence. Conclusions: The international RPS guidelines can guide current practice for surgeons, patients, medical societies, hospital administrators, and related social communities. Further randomized trials are required to determine the added value of RPS as compared to open and laparoscopic surgery.

The clinical implication of minimally invasive versus open pancreatoduodenectomy for non-pancreatic periampullary cancer: a systematic review and individual patient data meta-analysis.

BACKGROUND: Most studies on minimally invasive pancreatoduodenectomy (MIPD) combine patients with pancreatic and periampullary cancers even though there is substantial heterogeneity between these tumors. Therefore, this study aimed to evaluate the role of MIPD compared to open pancreatoduodenectomy (OPD) in patients with non-pancreatic periampullary cancer (NPPC). METHODS: A systematic review of Pubmed, Embase, and Cochrane databases was performed by two independent reviewers to identify studies comparing MIPD and OPD for NPPC (ampullary, distal cholangio, and duodenal adenocarcinoma) (01/2015-12/2021). Individual patient data were required from all identified studies. Primary outcomes were (90-day) mortality, and major morbidity (Clavien-Dindo 3a-5). Secondary outcomes were postoperative pancreatic fistula (POPF), delayed gastric emptying (DGE), postpancreatectomy hemorrhage (PPH), blood-loss, length of hospital stay (LOS), and overall survival (OS). RESULTS: Overall, 16 studies with 1949 patients were included, combining 928 patients with ampullary, 526 with distal cholangio, and 461 with duodenal cancer. In total, 902 (46.3%) patients underwent MIPD, and 1047 (53.7%) patients underwent OPD. The rates of 90-day mortality, major morbidity, POPF, DGE, PPH, blood-loss, and length of hospital stay did not differ between MIPD and OPD. Operation time was 67 min longer in the MIPD group (P = 0.009). A decrease in DFS for ampullary (HR 2.27, P = 0.019) and distal cholangio (HR 1.84, P = 0.025) cancer, as well as a decrease in OS for distal cholangio (HR 1.71, P = 0.045) and duodenal cancer (HR 4.59, P < 0.001) was found in the MIPD group. CONCLUSIONS: This individual patient data meta-analysis of MIPD versus OPD in patients with NPPC suggests that MIPD is not inferior in terms of short-term morbidity and mortality. Several major limitations in long-term data highlight a research gap that should be studied in prospective maintained international registries or randomized studies for ampullary, distal cholangio, and duodenum cancer separately. PROTOCOL REGISTRATION: PROSPERO (CRD42021277495) on the 25th of October 2021.

Minimally invasive surgery versus open surgery for total pancreatectomy: a bibliometric review and meta-analysis.

BACKGROUND: Minimally invasive total pancreatectomy (MITP) is considered safe and feasible with limited evidence on this procedure. The aim of this study was to systematically analyze the current literature on MITP compared to open TP (OTP). METHOD: Randomized controlled trials and prospective non-randomized comparative studies were sought systematically in MEDLINE, Web of Science and CENTRAL from their inception until December 2021. Outcome measures included operative time, length of hospital stay (LOH), spleen-preservation rate, estimated blood loss (EBL), need for transfusion, venous resection rate, delayed gastric emptying (DGE), biliary leakage, postpancreatectomy hemorrhage (PPH), reoperation rate, overall 30-day morbidity (Clavien-Dindo > IIIa), 90-day mortality, 90-day readmission, examined lymph nodes (ELN). Pooled results are presented as odds ratios (OR) or mean difference (MD) with 95% confidence interval (CI). RESULTS: 7 observational studies with a total of 4212 patients were included. MITP had a decreased EBL and transfusion rate, lower 30-day morbidity and 90-day mortality with a longer LOH compared to OTP. There were no significant differences regarding operative time, spleen preservation rate, DGE, biliary leakage, venous resection rate, PPH, reoperation, 90-day readmission and ELN. DISCUSSION: Based on the available studies, MITP is safe and feasible compared to OTP in highly experienced hands from high-volume centers. Further high-quality studies are needed to verify the conclusion.

Corrigendum: Clinical impact of molecular subtyping of pancreatic cancer.

[This corrects the article DOI: 10.3389/fcell.2021.743908.].

Minimally invasive versus open pancreatoduodenectomy for pancreatic ductal adenocarcinoma: Individual patient data meta-analysis of randomized trials.

OBJECTIVE: Assessment of minimally invasive pancreatoduodenectomy (MIPD) in patients with pancreatic ductal adenocarcinoma (PDAC) is scarce and limited to non-randomized studies. This study aimed to compare oncological and surgical outcomes after MIPD compared to open pancreatoduodenectomy (OPD) for patients after resectable PDAC from published randomized controlled trials (RCTs). METHODS: A systematic review was performed to identify RCTs comparing MIPD and OPD including PDAC (Jan 2015-July 2021). Individual data of patients with PDAC were requested. Primary outcomes were R0 rate and lymph node yield. Secondary outcomes were blood-loss, operation time, major complications, hospital stay and 90-day mortality. RESULTS: Overall, 4 RCTs (all addressed laparoscopic MIPD) with 275 patients with PDAC were included. In total, 128 patients underwent laparoscopic MIPD and 147 patients underwent OPD. The R0 rate (risk difference(RD) -1%, P = 0.740) and lymph node yield (mean difference(MD) +1.55, P = 0.305) were comparable between laparoscopic MIPD and OPD. Laparoscopic MIPD was associated with less perioperative blood-loss (MD -91ml, P = 0.026), shorter length of hospital stay (MD -3.8 days, P = 0.044), while operation time was longer (MD +98.5 min, P = 0.003). Major complications (RD -11%, P = 0.302) and 90-day mortality (RD -2%, P = 0.328) were comparable between laparoscopic MIPD and OPD. CONCLUSIONS: This individual patient data meta-analysis of MIPD versus OPD in patients with resectable PDAC suggests that laparoscopic MIPD is non-inferior regarding radicality, lymph node yield, major complications and 90-day mortality and is associated with less blood loss, shorter hospital stay, and longer operation time. The impact on long-term survival and recurrence should be studied in RCTs including robotic MIPD.

Ensemble deep learning enhanced with self-attention for predicting immunotherapeutic responses to cancers.

Introduction: Despite the many benefits immunotherapy has brought to patients with different cancers, its clinical applications and improvements are still hindered by drug resistance. Fostering a reliable approach to identifying sufferers who are sensitive to certain immunotherapeutic agents is of great clinical relevance. Methods: We propose an ELISE (Ensemble Learning for Immunotherapeutic Response Evaluation) pipeline to generate a robust and highly accurate approach to predicting individual responses to immunotherapies. ELISE employed iterative univariable logistic regression to select genetic features of patients, using Monte Carlo Tree Search (MCTS) to tune hyperparameters. In each trial, ELISE selected multiple models for integration based on add or concatenate stacking strategies, including deep neural network, automatic feature interaction learning via self-attentive neural networks, deep factorization machine, compressed interaction network, and linear neural network, then adopted the best trial to generate a final approach. SHapley Additive exPlanations (SHAP) algorithm was applied to interpret ELISE, which was then validated in an independent test set. Result: Regarding prediction of responses to atezolizumab within esophageal adenocarcinoma (EAC) patients, ELISE demonstrated a superior accuracy (Area Under Curve [AUC] = 100.00%). AC005786.3 (Mean [|SHAP value|] = 0.0097) was distinguished as the most valuable contributor to ELISE output, followed by SNORD3D (0.0092), RN7SKP72 (0.0081), EREG (0.0069), IGHV4-80 (0.0063), and MIR4526 (0.0063). Mechanistically, immunoglobulin complex, immunoglobulin production, adaptive immune response, antigen binding and others, were downregulated in ELISE-neg EAC subtypes and resulted in unfavorable responses. More encouragingly, ELISE could be extended to accurately estimate the responsiveness of various immunotherapeutic agents against other cancers, including PD1/PD-L1 suppressor against metastatic urothelial cancer (AUC = 88.86%), and MAGE-A3 immunotherapy against metastatic melanoma (AUC = 100.00%). Discussion: This study presented deep insights into integrating ensemble deep learning with self-attention as a mechanism for predicting immunotherapy responses to human cancers, highlighting ELISE as a potential tool to generate reliable approaches to individualized treatment.

IL-7: A promising adjuvant ensuring effective T cell responses and memory in combination with cancer vaccines?

Cancer vaccines exhibit specificity, effectiveness, and safety as an alternative immunotherapeutic strategy to struggle against malignant diseases, especially with the rapid development of mRNA cancer vaccines in recent years. However, how to maintain long-term immune memory after vaccination, especially T cells memory, to fulfill lasting surveillance against cancers, is still a challenging issue for researchers all over the world. IL-7 is critical for the development, maintenance, and proliferation of T lymphocytes, highlighting its potential role as an adjuvant in the development of cancer vaccines. Here, we summarized the IL-7/IL-7 receptor signaling in the development of T lymphocytes, the biological function of IL-7 in the maintenance and survival of T lymphocytes, the performance of IL-7 in pre-clinical and clinical trials of cancer vaccines, and the rationale to apply IL-7 as an adjuvant in cancer vaccine-based therapeutic strategy.

Comparison of safety and effectiveness between laparoscopic and open pancreatoduodenectomy: A systematic review and meta-analysis.

BACKGROUND: Validity of the laparoscopic approach in pancreatic head lesion remains debatable. This study aims to compare the safety and effectiveness of laparoscopic pancreatoduodenectomy (LPD) and open pancreatoduodenectomy (OPD) and investigate the source of heterogeneity from surgeons' and patients' perspectives. METHOD: We searched PubMed, Cochrane, Embase, and Web of Science for studies published before February 1, 2021. Of 6578 articles, 81 were full-text reviewed. The primary outcome was mortality. Three independent reviewers screened and extracted the data and resolved disagreements by consensus. Studies were evaluated for quality using ROB2.0 and ROBINS-I. According to different study designs, sensitivity and meta-regression analyses were conducted to explore the heterogeneity source. This meta-analyses was also conducted to explore the learning curve's heterogeneity. This study was registered with PROSPERO, CRD42021234579. RESULTS: We analyzed 34 studies involving 46,729 patients (4705 LPD and 42,024 OPD). LPD was associated with lower (P = 0.025) in unmatched studies (P = 0.017). No differences in mortality existed in randomized controlled trials (P = 0.854) and matched studies (P = 0.726). Sensitivity analysis found no significant difference in mortality in elderly patients, patients with pancreatic cancer, and in high- and low-volume hospitals (all P > 0.05). In studies at the early period of LPD (<40 cases), higher mortality (P < 0.001) was found (all P < 0.05).LPD showed non-inferiority in length of stay, complications, and survival outcomes in all analyses. CONCLUSION: In high-volume centers with adequate surgical experience, LPD in selected patients appears to be a valid alternative to LPD with comparable mortality, LOS, complications, and survival outcomes.

Safety and efficacy of TRIANGLE operation applied in pancreatic surgery: a protocol of the systematic review and meta-analysis.

BACKGROUND: Pancreatic surgery is regarded as the only curative treatment for pancreatic cancer (PC). As the neoadjuvant therapy is applied widely nowadays, the proportion of patients with PC undergoing surgery also with locally advanced tumour findings has increased accordingly. Especially in these situations, a radical resection of all tumour tissues is challenging. A novel surgical strategy has been introduced recently to achieve this aim, namely the TRIANGLE operation which comprises the radical resection of all nerve and lymphatic tissue between coeliac artery, superior mesenteric artery and mesenteric-portal axis without including extended lymphadenectomy outside this area. Due to currently published studies, Triangle Operation is a safe and feasible procedure. However, this has not been systematically analysed to date. This systematic review and meta-analysis aim to evaluate surgical and postoperative outcomes of Triangle Operation in pancreatic surgery. METHODS AND ANALYSIS: Pubmed, Web of Science and Cochrane Central Register of Controlled Trials in the Cochrane Library will be searched from inception until 31 December 2022. This study will include all articles comparing Triangle Operation versus non-Triangle Operation in pancreatic surgery to assess outcomes. The primary endpoints will be R0 resection rate and 1-year overall survival. The secondary endpoints will be delayed gastric emptying, postoperative pancreatic fistula, post pancreatectomy haemorrhages and reoperation incidence, overall complications, mortality and 3-year overall survival. The study selection, study quality assessment, data extraction and critical appraisal will be carried out by two reviewers. Inter-reviewer disagreements will be evaluated by discussion with a third reviewer. Besides, a subgroup analysis will be conducted focused on robotic surgery, laparoscopic surgery and open surgery in detail. Additionally, the Grading of Recommendations, Assessment, Development and Evaluations framework will be performed to evaluate the strength of evidence. ETHICS AND DISSEMINATION: This systematic review and meta-analysis will not require ethical approval. Results will be published in a peer-reviewed scientific journal. PROSPERO REGISTRATION NUMBER: CRD42021234721.

Clinical Impact of Molecular Subtyping of Pancreatic Cancer.

Pancreatic ductal adenocarcinoma is a highly lethal malignancy, which has now become the seventh most common cause of cancer death in the world, with the highest mortality rates in Europe and North America. In the past 30 years, there has been some progress in 5-year survival (rates increasing from 2.5 to 10%), but this is still extremely poor compared to all other common cancer types. Targeted therapies for advanced pancreatic cancer based on actionable mutations have been disappointing, with only 3-5% showing even a short clinical benefit. There is, however, a molecular diversity beyond mutations in genes responsible for producing classical canonical signaling pathways. Pancreatic cancer is almost unique in promoting an excess production of other components of the stroma, resulting in a complex tumor microenvironment that contributes to tumor development, progression, and response to treatment. Various transcriptional subtypes have also been described. Most notably, there is a strong alignment between the Classical/Pancreatic progenitor and Quasi-mesenchymal/Basal-like/Squamous subtype signatures of Moffit, Collinson, Bailey, Puleo, and Chan-Seng-Yue, which have potential clinical impact. Sequencing of epithelial cell populations enriched by laser capture microscopy combined with single-cell RNA sequencing has revealed the potential genomic evolution of pancreatic cancer as being a consequence of a gene expression continuum from mixed Basal-like and Classical cell populations within the same tumor, linked to allelic imbalances in mutant KRAS, with metastatic tumors being more copy number-unstable compared to primary tumors. The Basal-like subtype appears more chemoresistant with reduced survival compared to the Classical subtype. Chemotherapy and/or chemoradiation will also enrich the Basal-like subtype. Squamous/Basal-like programs facilitate immune infiltration compared with the Classical-like programs. The immune infiltrates associated with Basal and Classical type cells are distinct, potentially opening the door to differential strategies. Single-cell and spatial transcriptomics will now allow single cell profiling of tumor and resident immune cell populations that may further advance subtyping. Multiple clinical trials have been launched based on transcriptomic response signatures and molecular subtyping including COMPASS, Precision Promise, ESPAC6/7, PREDICT-PACA, and PASS1. We review several approaches to explore the clinical relevance of molecular profiling to provide optimal bench-to-beside translation with clinical impact.

Surgical Treatment of Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) represents an aggressive tumor of the digestive system with still low five-year survival of less than 10%. Although there are improvements for multimodal therapy of PDAC, surgery still remains the effective way to treat the disease. Combined with adjuvant and/or neoadjuvant treatment, pancreatic surgery is able to enhance the five-year survival up to around 20%. However, pancreatic resection is always associated with a high risk of complications and regarded as one of the most complex fields in abdominal surgery. This review gives a summary on the surgical treatment for PDAC based on the current literature with a special focus on resection techniques.

CT, MRI, and F-18 FDG PET for the detection of non-small-cell lung cancer (NSCLC): A protocol for a network meta-analysis of diagnostic test accuracy.

BACKGROUND: Non-small-cell lung cancer (NSCLC) is a rare cancer in lung carcinomas and has been widely known as a difficult curable disease among all the tumors. However, early detection of malignant potential in patients with NSCLC has still been a huge challenge all around the world. CT, MRI, and F-18 FDG PET are all considered as good tests for diagnosing malignant NSCLC efficiently, but no recommended suggestion presents that which test among the 3 is the prior one in diagnose. We perform this study through network meta-analysis method, and to rank these tests using a superiority index. METHODS AND ANALYSIS: PubMed, Embase.com, and the Cochrane Central Register of Controlled Trials (CENTRAL) will be searched from their inception to March 2018. We will include diagnostic tests which assessed the accuracy of CT, MRI, and F-18 FDG PET for diagnosing NSCLC. The risk of bias for each study will be independently assessed as low, moderate, or high using criteria adapted from Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). Network meta-analysis will be performed using STATA 12.0 and R 3.4.1 software. The competing diagnostic tests will be ranked by a superiority index. RESULTS: This study is ongoing, and will be submitted to a peer-reviewed journal for publication. CONCLUSION: This study will provide systematically suggestions to select different diagnostic measures for detecting the early NSCLC. ETHICS AND DISSEMINATION: Ethical approval and patient consent are not required since this study is a network meta-analysis based on published studies. The results of this network meta-analysis will be submitted to a peer-reviewed journal for publication. PROSPERO REGISTRATION NUMBER: PROSPEROCRD42018094542.

The clinicopathological factors associated with prognosis of patients with resectable perihilar cholangiocarcinoma: A systematic review and meta-analysis.

The refinement in surgical techniques combined with the preoperative management has improved the resectability rate of perihilar cholangiocarcinoma (pCCA). However, the prognosis of pCCA with curative resection is still dismal. This meta-analysis was performed to investigate the prognostic clinicopathological factors in resectable pCCA.PubMed, the Cochran Library, ScienceDirect, and Web of Science were searched systematically to identify reports focusing on studying the prognostic clinicopathological factors in resectable pCCA. The hazard ratios (HRs) and its 95% confidence interval (95%CI) from the identified studies using Cox proportional hazard regression model were extracted for overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) analysis.Three prospective and 35 retrospective cohort studies including 5681 resectable pCCA were included in the pooled analysis. Among more than 20 clinicopathological factors associated with negative survival of pCCA, only 6 were included in quantitative analysis which showed that lymph node involvement was associated with a reduced OS (HR = 2.04; 95%CI: 2.10-2.62), DSS (HR = 1.80; 95%CI: 1.39-2.34), DFS (HR = 4.38; 95%CI: 1.89-10.14), negative resection margin (HR = 2.04; 95%CI:1.73-2.41), operative transfusion (HR = 1.82; 95%CI: 1.06-3.11), and T3 or T4-stage (HR = 2.04; 95%CI: 2.04-2.53) were poor prognostic factors of OS, and poor or moderate differentiation was also an adverse prognostic factor of OS (HR = 2.71; 95%CI: 1.80-4.07) and DSS (HR = 1.74; 95%CI: 1.25-2.44). The overall median resectability rate (95CI%), R0 resection (95CI%), and 5-year OS (95CI%) in Eastern and Western countries were 74.9 (66.4-78.4) % and 41.3 (32.6-80.8) %, 70.7 (65.6-80.8) % and 75.9 (64.0-80.4) %, and 33.0 (29.7-39.7) % and 25.5 (20.0-31.6) %, respectively.Negative resection margin, lymph node involvement, poor or moderate differentiation grade was identified as the negative predictor factors of resectable pCCA. Operative transfusion and T3/T4 stage were also associated with a reduced survival of resectable pCCA.

Five common tumor biomarkers and CEA for diagnosing early gastric cancer: A protocol for a network meta-analysis of diagnostic test accuracy.

BACKGROUND: Although surgical resection is the recommended treatment for the patients with gastric cancer, lots of patients show advanced or metastatic gastric cancer at the time of diagnosis. Detection of gastric cancer at early stages is a huge challenge because of lack of appropriate detection tests. Unfortunately, existing clinical guidelines focusing on early diagnosis of gastric cancer do not provide consistent and prudent evidence. Serum carcinoembryonic antigen was considered as a complementary test, although it is not good enough to diagnose early gastric cancer. There are no other tumor markers recommended for diagnosing early gastric cancer. This study aims to evaluate and compare the diagnostic accuracy of 5 common tumor biomarkers (CA19-9, CA125, PG, IncRNA, and DNA methylation) and CEA and their combinations for diagnosing gastric cancer through network meta-analysis method, and to rank these tests using a superiority index. METHODS: PubMed, EMBASE.com, and the Cochrane Central Register of Controlled Trials (CENTRAL) will be searched from their inception to March 2018. We will include diagnostic tests which assessed the accuracy of the above-mentioned tumor biomarkers and CEA for diagnosing gastric cancer. The risk of bias for each study will be independently assessed as low, moderate, or high using criteria adapted from Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). Network meta-analysis will be performed using STATA 12.0 and R 3.4.1 software. The competing diagnostic tests will be ranked by a superiority index. RESULTS: This study is ongoing and will be submitted to a peer-reviewed journal for publication. CONCLUSION: This study will provide systematically suggestions to select different tumor biomarkers for detecting the early gastric cancer.

F-18 FDG PET, CT, and MRI for detecting the malignant potential in patients with gastrointestinal stromal tumors: A protocol for a network meta-analysis of diagnostic test accuracy.

BACKGROUND: Gastrointestinal stromal tumor (GIST) is a rare cancer in gastrointestinal carcinomas and has been widely known as a curable disease among all the digestive tumors. However, early detection of malignant potential in patients with GIST has still been a huge challenge all around the world. CT, MRI, and F-18 FDG PET are all considered as good tests for diagnosing malignant GIST efficiently, but no recommended suggestions presents which test among the 3 is the prior one in detecting the malignant potential of GIST. We perform this study to assess the accuracy between CT, MRI, and F-18 FDG PET through network meta-analysis method, and to rank these tests. METHODS AND ANALYSIS: PubMed, EMBASE.com, CNKI, and CBM databases will be searched without search date and language restrictions. We will include diagnostic tests which assessed the accuracy of CT, MRI, and F-18 FDG PET in detecting the malignant potential of GIST. The risk of bias in each study will be independently assessed as low, moderate, or high using criteria adapted from Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). Meta-analysis will be performed using STATA 12.0 and R 3.4.1 software. The competing diagnostic tests will be ranked by a superiority index. RESULTS: This study is ongoing, and will be submitted to a peer-reviewed journal for publication. CONCLUSION: This study will provide a comprehensive evidence summary of CT, MRI, and F-18 FDG PET in detecting the malignant potential of GIST.

Different types of mesh fixation for laparoscopic repair of inguinal hernia: A protocol for systematic review and network meta-analysis with randomized controlled trials.

BACKGROUND: Laparoscopic inguinal hernia repair has become a valid option for repair of an inguinal hernia. Due to there are several types of mesh fixation for laparoscopic repair of inguinal hernia. The study aims to assess and compare the efficacy of different types of mesh fixation for laparoscopic repair of inguinal hernia using network meta-analysis. METHODS: We will systematically search PubMed, EMBASE the Cochrane library, and Chinese Biomedical Literature Database from their inception to March 2018. Randomized controlled trials (RCTs) that compared the effect of different types of mesh fixation for laparoscopic inguinal hernia repair will be included. The primary outcomes are chronic groin pain, incidence risk of hernia recurrence, and complications. Risk of bias assessment of the included RCTs will be conducted using to Cochrane risk of bias tool. A network meta-analysis will be performed using WinBUGS 1.4.3 software and the result figures will be generated using R x64 3.1.2 software and STATA V.12.0 software. Grading of Recommendations Assessment, Development and Evaluation (GRADE) will be used to assess the quality of evidence. RESULTS: The results of this study will be published in a peer-reviewed journal. CONCLUSION: Our study will generate evidence of laparoscopic repair of mesh fixation for adult patients with inguinal hernia and provide suggestions for clinical practice or guideline.