The gut microbiome dysbiosis and regulation by fecal microbiota transplantation: umbrella review.

Background: Gut microbiome dysbiosis has been implicated in various gastrointestinal and extra-gastrointestinal diseases, but evidence on the efficacy and safety of fecal microbiota transplantation (FMT) for therapeutic indications remains unclear. Methods: The gutMDisorder database was used to summarize the associations between gut microbiome dysbiosis and diseases. We performed an umbrella review of published meta-analyses to determine the evidence synthesis on the efficacy and safety of FMT in treating various diseases. Our study was registered in PROSPERO (CRD42022301226). Results: Gut microbiome dysbiosis was associated with 117 gastrointestinal and extra-gastrointestinal. Colorectal cancer was associated with 92 dysbiosis. Dysbiosis involving Firmicutes (phylum) was associated with 34 diseases. We identified 62 published meta-analyses of FMT. FMT was found to be effective for 13 diseases, with a 95.56% cure rate (95% CI: 93.88-97.05%) for recurrent Chloridoids difficile infection (rCDI). Evidence was high quality for rCDI and moderate to high quality for ulcerative colitis and Crohn's disease but low to very low quality for other diseases. Conclusion: Gut microbiome dysbiosis may be implicated in numerous diseases. Substantial evidence suggests FMT improves clinical outcomes for certain indications, but evidence quality varies greatly depending on the specific indication, route of administration, frequency of instillation, fecal preparation, and donor type. This variability should inform clinical, policy, and implementation decisions regarding FMT.

The SUPER reporting guideline suggested for reporting of surgical technique.

Background: Existing reporting guidelines pay insufficient attention to the detail and comprehensiveness reporting of surgical technique. The Surgical techniqUe rePorting chEcklist and standaRds (SUPER) aims to address this gap by defining reporting standards for surgical technique. The SUPER guideline intends to apply to articles that encompass surgical technique in any study design, surgical discipline, and stage of surgical innovation. Methods: Following the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) Network approach, 16 surgeons, journal editors, and methodologists reviewed existing reporting guidelines relating to surgical technique, reviewed papers from 15 top journals, and brainstormed to draft initial items for the SUPER. The initial items were revised through a three-round Delphi survey from 21 multidisciplinary Delphi panel experts from 13 countries and regions. The final SUPER items were formed after an online consensus meeting to resolve disagreements and a three-round wording refinement by all 16 SUPER working group members and five SUPER consultants. Results: The SUPER reporting guideline includes 22 items that are considered essential for good and informative surgical technique reporting. The items are divided into six sections: background, rationale, and objectives (items 1 to 5); preoperative preparations and requirements (items 6 to 9); surgical technique details (items 10 to 15); postoperative considerations and tasks (items 16 to 19); summary and prospect (items 20 and 21); and other information (item 22). Conclusions: The SUPER reporting guideline has the potential to guide detailed, comprehensive, and transparent surgical technique reporting for surgeons. It may also assist journal editors, peer reviewers, systematic reviewers, and guideline developers in the evaluation of surgical technique papers and help practitioners to better understand and reproduce surgical technique. Trial Registration: https://www.equator-network.org/library/reporting-guidelines-under-development/reporting-guidelines-under-development-for-other-study-designs/#SUPER.

The SUPER reporting guideline suggested for reporting of surgical technique: explanation and elaboration.

Background: Surgical technique plays an essential role in achieving good health outcomes. However, the quality of surgical technique reporting remains heterogeneous. Reporting checklists could help authors to describe the surgical technique more transparently and effectively, as well as to assist reviewers and editors evaluate it more informatively, and promote readers to better understand the technique. We previously developed SUPER (surgical technique reporting checklist and standards) to assist authors in reporting their research that contains surgical technique more transparently. However, further explanation and elaboration of each item are needed for better understanding and reporting practice. Methods: We searched surgical literature in PubMed, Google Scholar and journal websites published up to January 2023 to find multidiscipline examples in various article types for each SUPER item. Results: We explain the 22 items of the SUPER and provide rationales item by item alongside. We provide 69 examples from 53 literature that present optimal reporting of the 22 items. Article types of examples include pure surgical technique, and case reports, observational studies and clinical trials that contain surgical technique. Examples are multidisciplinary, including general surgery, orthopaedical surgery, cardiac surgery, thoracic surgery, gastrointestinal surgery, neurological surgery, oncogenic surgery, and emergency surgery etc. Conclusions: Along with SUPER article, this explanation and elaboration file can promote deeper understanding on the SUPER items. We hope that the article could further guide surgeons and researchers in reporting, and assist editors and peer reviewers in reviewing manuscripts related to surgical technique.

A novel adenosine signalling-based prognostic signature in gastric cancer and its association with cancer immune features and immunotherapy response.

Reliable prognostic signatures that can reflect the intrinsic characteristics of gastric cancer (GC) are still rare. Here, we developed an adenosine-based prognostic signature and explored its association with the tumour immune in GC patients, aiming at confirming the prognostic value of adenosine-related genes and guiding the GC risk stratification and immunotherapeutic response prediction. We collected adenosine pathway-related genes from STRING websites and manual searching. We enrolled the The Cancer Genome Atlas cohort and four gene expression omnibus cohorts of GC for generating and validating the adenosine pathway-based signature using the Cox regression method. Gene expression in the signature was verified using polymerase chain reaction. We also performed gene set enrichment analysis, immune infiltration assessment and immunotherapy response prediction based on this signature. Our study resulted in a six-gene adenosine signature (GNAS, CXCR4, PPP1R1B, ADCY6, NT5E and NOS3) for risk stratification of GC prognosis, with the highest area under the receiver operating characteristic curve up to 0.767 for predicting 10-year overall survival (OS). In the training cohort, patients with signature-defined high risk had significantly poorer OS than those with low risk (p < .001). Multivariate analysis identified the signature as an independent prognostic factor (hazard ratio 2.863, 95% confidence interval [1.871-4.381], p < .001). These findings were confirmed in four independent cohorts. Expression detection showed that all signature genes were upregulated in both GC tissues and cell lines. Further analysis revealed that the signature-defined high-risk patients were characterised by immunosuppressive states and associated with a poor immunotherapy response. In conclusion, the adenosine pathway-based signature represents a promising risk stratification tool for GC in guiding individualised prognostication and immunotherapy.

Effectiveness of intraoperative peritoneal lavage with saline in patient with intra-abdominal infections: a systematic review and meta-analysis.

BACKGROUND: Intraoperative peritoneal lavage (IOPL) with saline has been widely used in surgical practice. However, the effectiveness of IOPL with saline in patients with intra-abdominal infections (IAIs) remains controversial. This study aims to systematically review randomized controlled trials (RCTs) evaluating the effectiveness of IOPL in patients with IAIs. METHODS: The databases of PubMed, Embase, Web of Science, Cochrane library, CNKI, WanFang, and CBM databases were searched from inception to December 31, 2022. Random-effects models were used to calculate the risk ratio (RR), mean difference, and standardized mean difference. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to rate the quality of the evidence. RESULTS: Ten RCTs with 1318 participants were included, of which eight studies on appendicitis and two studies on peritonitis. Moderate-quality evidence showed that the use of IOPL with saline was not associated with a reduced risk of mortality (0% vs. 1.1%; RR, 0.31 [95% CI, 0.02-6.39]), intra-abdominal abscess (12.3% vs. 11.8%; RR, 1.02 [95% CI, 0.70-1.48]; I2 = 24%), incisional surgical site infections (3.3% vs. 3.8%; RR, 0.72 [95% CI, 0.18-2.86]; I2 = 50%), postoperative complication (11.0% vs. 13.2%; RR, 0.74 [95% CI, 0.39-1.41]; I2 = 64%), reoperation (2.9% vs. 1.7%; RR,1.71 [95% CI, 0.74-3.93]; I2 = 0%) and readmission (5.2% vs. 6.6%; RR, 0.95 [95% CI, 0.48-1.87]; I2 = 7%) in patients with appendicitis when compared to non-IOPL. Low-quality evidence showed that the use of IOPL with saline was not associated with a reduced risk of mortality (22.7% vs. 23.3%; RR, 0.97 [95% CI, 0.45-2.09], I2 = 0%) and intra-abdominal abscess (5.1% vs. 5.0%; RR, 1.05 [95% CI, 0.16-6.98], I2 = 0%) in patients with peritonitis when compared to non-IOPL. CONCLUSION: IOPL with saline use in patients with appendicitis was not associated with significantly decreased risk of mortality, intra-abdominal abscess, incisional surgical site infection, postoperative complication, reoperation, and readmission compared with non-IOPL. These findings do not support the routine use of IOPL with saline in patients with appendicitis. The benefits of IOPL for IAI caused by other types of abdominal infections need to be investigated.

Photodynamic therapy combined with systemic chemotherapy for unresectable extrahepatic cholangiocarcinoma: A systematic review and meta-analysis.

BACKGROUND: Extrahepatic cholangiocarcinoma (ECC) is a tumor with high invasiveness and poor outcome. The current treatments for unresected ECC are not ideal. Novel strategies are needed to improve the outcomes of patients with unresected ECC. Photodynamic therapy (PDT) plus chemotherapy is one of the promising interventions for ECC patients. We conducted this systematic review to determine the efficacy and safety of PDT plus chemotherapy in unresected ECC patients. METHODS: Databases of PubMed, Cochrane Library, Embase, and Web of science were searched from inception to July 2022. Studies that compared PDT plus chemotherapy to PDT alone or chemotherapy alone in patients with unresected ECC were included. Hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were pooled for overall survival (OS) and adverse events, respectively. RESULTS: Seven eligible studies were finally included. There are four studies on PDT plus chemotherapy vs. chemotherapy alone and three studies on PDT plus chemotherapy vs. PDT alone. The meta-analysis showed that PDT plus chemotherapy had a significantly better OS than chemotherapy or PDT alone (PDT+chemotherapy vs. chemotherapy alone, HR: 0.69, p = 0.02; PDT+chemotherapy vs. PDT alone, HR:0.36, p<0.01). The occurrence of cholangitis, abscess, and photosensitivity reaction in PDT plus chemotherapy were comparable to either chemotherapy alone or PDT alone (p>0.05). CONCLUSION: The combination of PDT and chemotherapy can improve patient survival for unresected ECC without increased adverse events. It may be a potential standard therapy in the future management of ECC.

Photodynamic therapy in combination with immune checkpoint inhibitors plus chemotherapy for first-line treatment in advanced or metastatic gastric or gastroesophageal junction cancer: A phase 2-3 clinical trial protocol.

Introduction: The immune checkpoint inhibitor (ICI) has been approved as the first-line therapy for metastatic gastric cancer in China. The treatment response of immune checkpoint inhibitor is highly dependent on the immune condition within the tumor microenvironment. Photodynamic therapy (PDT) has a long history in cancer treatment, and recent studies showed it had an immunomodulatory effect on the tumor. Here we will conduct a trial to assess whether or not a combination with Photodynamic therapy will improve the outcomes of immune checkpoint inhibitor-based treatment in patients with advanced or metastatic gastric cancer. Methods: This study is a single-center, open-label, randomized controlled, phase 2-3 trial. Patients (18-65 years old) with untreated gastric or gastroesophageal junction adenocarcinoma will be eligible for this trial. Sixty participants will be enrolled and randomly divided into the test group (n = 30) and control group (n = 30) to receive photodynamic therapy in combination with immune checkpoint inhibitor plus chemotherapy and immune checkpoint inhibitor plus chemotherapy, respectively. The primary is progression-free survival (PFS). The secondary outcomes include objective response rates (ORRs) and the occurrence of adverse events. In addition, we will also assess the changes in peripheral blood mononuclear cells (PBMCs) and tumor microenvironment after photodynamic therapy treatment in the test group. Evaluation of the tumor response will be performed every two cycles for a maximum of eight cycles. Discussion: Photodynamic therapy has an immunomodulatory effect on the tumor microenvironment; however, this has not been demonstrated for gastric cancer in a clinical trial. Based on our experience of photodynamic therapy treatment in digestive tract tumors, we plan to conduct a randomized controlled trial on this topic. This will be the first study to evaluate the synergistic effect of photodynamic therapy with immunochemotherapy for patients with advanced gastric cancer. Ethics and dissemination: It was approved by the Institutional Research Ethics Committee of Lanzhou University Second Hospital (No. 2022A-491). When this trial is completed, it will be shared at conferences and submitted for a potential publication in a peer-reviewed journal. Clinical Trial Registration: http://www.chictr.org.cn/, identifier ChiCTR2200064280.

Reporting guidelines for surgical technique could be improved: a scoping review and a call for action.

OBJECTIVES: To identify reporting guidelines related to surgical technique and propose recommendations for areas that require improvement. STUDY DESIGN AND SETTING: A protocol-guided scoping review was conducted. A literature search of MEDLINE, the EQUATOR Network Library, Google Scholar, and Networked Digital Library of Theses and Dissertations was conducted to identify surgical technique reporting guidelines published up to December 31, 2021. RESULTS: We finally included 55 surgical technique reporting guidelines, vascular surgery (n = 18, 32.7%) was the most common among the clinical specialties covered. The included guidelines generally showed a low degree of international and multidisciplinary cooperation. Few guidelines provided a detailed development process (n = 14, 25.5%), conducted a systematic literature review (n = 13, 23.6%), used the Delphi method (n = 4, 7.3%), or described post-publication strategy (n = 6, 10.9%). The vast majority guidelines focused on the reporting of intraoperative period (n = 50, 90.9%). However, of the guidelines requiring detailed descriptions of surgical technique methodology (n = 43, 78.2%), most failed to provide guidance on what constitutes an adequate description. CONCLUSION: Our study demonstrates significant deficiencies in the development methodology and practicality of reporting guidelines for surgical technique. A standardized reporting guideline that is developed rigorously and focuses on details of surgical technique may serve as a necessary impetus for change.

A meta-analysis of based radiomics for predicting lymph node metastasis in patients with biliary tract cancers.

Background: To assess the predictive value of radiomics for preoperative lymph node metastasis (LMN) in patients with biliary tract cancers (BTCs). Methods: PubMed, Embase, Web of Science, Cochrane Library databases, and four Chinese databases [VIP, CNKI, Wanfang, and China Biomedical Literature Database (CBM)] were searched to identify relevant studies published up to February 10, 2022. Two authors independently screened all publications for eligibility. We included studies that used histopathology as a gold standard and radiomics to evaluate the diagnostic efficacy of LNM in BTCs patients. The quality of the literature was evaluated using the Radiomics Quality Score (RQS) and the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). The diagnostic odds ratio (DOR), sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and area under the receiver operating characteristic curve (AUC) were calculated to assess the predictive validity of radiomics for lymph node status in patients with BTCs. Spearman correlation coefficients were calculated, and Meta-regression and subgroup analyses were performed to assess the causes of heterogeneity. Results: Seven studies were included, with 977 patients. The pooled sensitivity, specificity and AUC were 83% [95% confidence interval (CI): 77%, 88%], 78% (95% CI: 71, 84) and 0.88 (95% CI: 0.85, 0.90), respectively. The substantive heterogeneity was observed among the included studies (I 2 = 80%, 95%CI: 58,100). There was no threshold effect seen. Meta-regression showed that tumor site contributed to the heterogeneity of specificity analysis (P < 0.05). Imaging methods, number of patients, combined clinical factors, tumor site, model, population, and published year all played a role in the heterogeneity of the sensitivity analysis (P < 0.05). Subgroup analysis revealed that magnetic resonance imaging (MRI) based radiomics had a higher pooled sensitivity than contrast-computed tomography (CT), whereas the result for pooled specificity was the opposite. Conclusion: Our meta-analysis showed that radiomics provided a high level of prognostic value for preoperative LMN in BTCs patients.

Developing the surgical technique reporting checklist and standards: a study protocol.

BACKGROUND: Standardized and transparent reporting of surgical technique is the cornerstone of effective dissemination, implementation and improvement. However, current reporting of surgical techniques is inadequate. The existing guidelines potentially applied to guide surgical technique reporting are with a minimal highlight of the surgical technique, lack requirements explaining what extent and dimensions need to be described in detail, or are unlikely to extrapolate to a wide range of surgical techniques. This study aims to formulate a rigorous protocol to develop a surgical technique reporting checklist and standards (SUPER) that defines what a clear, comprehensive and detailed surgical technique report should be contained. METHODS: This protocol is designed following the classic guidance for developing reporting guidelines recommended by the EQUATOR network. RESULTS: The development team will consist of surgeons (~80%), methodologists, and journal editors. The draft checklist sources will include a scoping review of existing reporting guidelines related to surgical technique, surgical technique articles from 15 top journals published in the last year, and brainstorming by the multidisciplinary development team. The final SUPER checklist will be formed after three rounds of Delphi surveys, one round of face-to-face meeting, and a month-long pilot test. The SUPER checklist will be published as open-access and be used in combination with existing reporting guidelines related to surgical techniques (e.g., IDEAL). This protocol will steer the SUPER checklist's development, allowing us to further elaborate surgical technique reporting for all surgical specialties, and enabling a more favorable experience for surgeons, nurses, medical students, residents, editors, and reviewers. TRIAL REGISTRATION: This trial is registered at the EQUATOR network on December 18th, 2020. Available at: https://www.equator-network.org/library/reporting-guidelines-under-development/reporting-guidelines-under-development-for-other-study-designs/.

Evidence on reporting guidelines for surgical technique in clinical disciplines: a scoping review protocol.

BACKGROUND: The reporting of surgical techniques is of mixed quality, with most at a very minimal level. Reporting guidelines that could be applied to guide surgical technique reporting vary in methodology for development, discipline coverage, dimension coverage and detail requested. However, a scoping review that could indicate the gaps and efforts needed in surgical technique reporting guidelines is lacking and warranted. This study aims to design a methodological rigour protocol to guide the development of a scoping review of surgical technique reporting guidelines. METHODS: This protocol is designed following the 2020 manual proposed by the Joanna Briggs Institute. To further ensure the soundness of the protocol, we also included multidisciplinary professionals (including methodologists, clinicians, and journal editors) to refine the protocol. DISCUSSION: Seven key steps for developing the scoping review are identified and presented in detail, including (I) identifying the research questions; (II) inclusion criteria; (III) search strategy; (IV) source of evidence selection; (V) data extraction; (VI) analysis of the evidence; and (VII) presentation of the results. Guided by this protocol, the subsequent scoping review will inform us the overview of surgical technique reporting guidelines and precisely guide our direction and next steps in improving surgical technique reporting guidelines. TRIAL REGISTRATION: This protocol is not registered as the PROSPERO database only accepts registration of systematic review protocols while does not accept registration of scoping review protocols.

Effects of Antibiotic Use on Outcomes in Cancer Patients Treated Using Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis.

Antibiotic (ATB) use seems to negatively affect the outcomes of immune checkpoint inhibitors (ICIs). The aim of this review is to clarify whether ATB use influences the efficacy of ICI treatment in cancer patients. Databases of MEDLINE, Embase, and Cochrane Library were searched for reports published in English between January 2007 and December 2019. We included studies that compared the outcomes of ATB use and no-ATB use in cancer patients using ICIs. Two reviewers independently selected eligible studies and extracted the data. Meta-analysis was performed with pooling of unadjusted hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and with pooling of odds ratios (ORs) for objective response rate (ORR). Thirty-eight studies involving 8409 patients were finally included for qualitative or quantitative analyses. Cancer types included renal cell carcinoma, non-small cell lung cancer, urothelial carcinoma, melanoma, gastrointestinal cancer, and others. Meta-analyses revealed that ATB use was associated with poor OS [HR: 1.80, 95% confidence interval (CI): 1.44-2.26, P<0.001], PFS (HR: 1.55, 95% CI: 1.26-1.91, P<0.001) and ORR (OR: 0.63, 95% CI: 0.42-0.95, P=0.03). Subgroup analysis found that these relationships were not influenced by cancer type or ICI regimens, but were dependent on the timing of ATB use. Narrative results of multivariable analyses further confirmed the negative effects of ATB use on OS and PFS. In cancer patients using ICIs, pre-ATB use close to the start of ICI treatment (within 60 d) was detrimental to outcomes in terms of OS, PFS, and ORR.

Prognostic significance of tissue factor in patients with pancreatic cancer: a systematic review protocol.

INTRODUCTION: Pancreatic cancer is a highly aggressive digestive system tumour with poor prognosis. Venous thromboembolism (VTE) is a well-known complication of pancreatic cancer, and tissue factor (TF) contributes to the generation of a hypercoagulable state and thrombotic disease in pancreatic cancer. Several studies showed that an elevated TF level was related to the development of VTE and influenced the survival of patients with pancreatic cancer. Thus, we wish to conduct a systematic review of literature to clarify the prognostic significance of TF in pancreatic cancer. METHODS AND ANALYSIS: Studies comparing the circulating microparticle-associated TF (MP TF) level between patients who had pancreatic cancer with and without VTE will be included to evaluate the roles of TF in VTE development. Studies comparing the survival data between patients with high TF expression and low TF expression will also be included to explore the association of TF expression with patient survival. The outcomes are plasma MP TF level and survival endpoints (overall and progression-free survival), respectively. Primary studies of any type published in English will be included. Two reviewers will search Medline, EMBASE and Cochrane databases from inception to June 2020, retrieve relevant studies, and independently select the literatures and extract data from the included studies. The quality of each included study will be assessed by the Newcastle-Ottawa Scale score. The HR and 95% CI of each study will be pooled for survival outcome, and the standardised mean difference (SMD) with 95% CIs will be used for continuous outcomes. If meta-analysis is inappropriate, the result will only be reported qualitatively. Subgroup and sensitivity analyses will be considered to identify sources of heterogeneity. The Grades of Recommendation, Assessment, Development and Evaluation method will be applied to assess the level of evidence of this systematic review. ETHICS AND DISSEMINATION: There are no concerning ethical issues. The results will be published. PROSPERO REGISTRATION NUMBER: CRD42019133665.

Effectiveness of intraoperative peritoneal lavage (IOPL) with saline in patient with intra-abdominal infections: a systematic review and meta-analysis protocol.

INTRODUCTION: Intra-abdominal infections (IAIs) are common surgical emergencies and cause a significant worldwide burden per year. Since the concept of intraoperative peritoneal lavage (IOPL) was proposed in 1905, it has been widely used in the surgery practice. However, the effectiveness of IOPL in patients with IAIs has always been controversial. Our objective is to identify whether it is beneficial to flush the abdominal cavity with saline in IAIs surgery through a comprehensive systematic review and meta-analysis. METHODS AND ANALYSIS: This protocol is reported in line with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. Electronic databases (including the Cochrane library, MEDLINE, EMBASE, Web of Science, etc) and clinical trial registry platforms will be searched from inception to 8 September 2019. Randomised controlled trials, quasi-randomised clinical trials and cohort studies comparing IOPL and suction alone in IAIs will be included. The primary outcomes are mortality and abscess rate. Two independent reviewers will screen literature, collect data and assess risk of bias of included studies. Discussion or a third reviewer will be referred for any disagreements. The Grading of Recommendations Assessment, Development and Evaluation approach will be used to assess the quality of the evidence. We will perform meta-analysis using random-effects model. Subgroup analysis, sensitivity analysis and publication bias will be conducted if data are enough. ETHICS AND DISSEMINATION: Ethical approval is not required for this systematic review and meta-analysis protocol. Results of this study will be published in a peer-reviewed journal, presented at relevant conferences and disseminated to local and international policy makers. PROSPERO REGISTRATION NUMBER: CRD42019145109.

Advances in the techniques and methodologies of cancer gene therapy.

Cancer is the second leading cause of mortality worldwide after cardiovascular diseases, predominantly due to the lack of early symptoms and early diagnosis, and high relapse rate after radical surgery and conventional therapies. Therefore, novel approaches such as gene therapy have raised hope to significantly improve the survival rate of patients with cancers. This review aims to provide up-to-date information concerning gene therapy including improved vectors, suicide genes, cancer suppressor genes, anti-tumor angiogenesis, gene silencing, oncolytic virotherapy, and gene-editing technology. Although specific issues still exist before gene therapy can completely cure cancers, here we highlight the potential of gene therapy in cancer treatment and expect to see continuous breakthroughs in techniques and methodologies of gene therapy.