Safety of first-line systemic therapy in patients with metastatic colorectal cancer: a network meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate the safety of first-line systemic therapy for metastatic colorectal cancer through network meta-analysis. METHODS: The literature from PubMed, Embase, Web of Science, and Cochrane Library databases was searched from the inception of the databases to August 15, 2023, and strict inclusion and exclusion criteria were applied to screen studies. The Cochrane Bias Risk Assessment Tool (RoB 2.0) was used to evaluate the quality of the included literature. Network meta-analysis was conducted using Stata 15.0 and R4.3.1 software to compare the incidence of adverse events (AEs) among different treatment regimens. RESULTS: A total of 53 randomized controlled trials, involving 17,351 patients with metastatic colorectal cancer (mCRC), were ultimately included, encompassing 29 different therapeutic approaches. According to SUCRA rankings, the CAPOX regimen is most likely to rank first in terms of safety, while the FOLFOXIRI + panitumumab regimen is most likely to rank last. In terms of specific AEs, the CAPOX regimen, whether used alone or in combination with targeted drugs (bevacizumab and cetuximab), is associated with a reduced risk of neutropenia and febrile neutropenia, as well as an increased risk of thrombocytopenia and diarrhea. The FOLFOX regimen, with or without bevacizumab, is linked to an increased risk of neutropenia and peripheral sensory neuropathy. The FOLFIRI/CAPIRI + bevacizumab regimen is associated with a reduced risk of peripheral sensory neuropathy. S-1 and S-1 + oxaliplatin are well-tolerated in terms of gastrointestinal reactions. The FOLFOXIRI regimen, whether used alone or in combination with targeted drugs, is associated with various AEs. CONCLUSION: In summary, the CAPOX regimen may be the safest option among the first-line systemic treatment regimens for mCRC patients, while the FOLFOXIRI + panitumumab regimen may be associated with a higher incidence of grade 3 or higher AEs.

Surgical, oncological, and functional outcomes of local and radical resection after neoadjuvant chemotherapy or chemoradiotherapy for early- and mid-stage rectal cancer: a systematic review and meta-analysis.

BACKGROUND: Radical resection is typically the standard treatment for early- and mid-stage rectal cancer as local resection may result in a high rate of recurrence and risk of distant metastasis. A growing number of studies have shown that local excision after neoadjuvant chemotherapy or chemoradiotherapy can significantly reduce recurrence rates and is a feasible strategy to preserve the rectum as an alternative to conventional radical resection. OBJECTIVE: This study aims to compare the efficacy of local resection after neoadjuvant chemotherapy or chemoradiotherapy with radical surgery for early- and mid-stage rectal cancer and to report the evidence-based clinical advantages of both techniques. METHODS: Clinical trials comparing oncologic and perioperative outcomes of local and radical resection after neoadjuvant chemotherapy or chemoradiotherapy in patients with early- to mid-stage rectal cancer were searched in PubMed, Embase, Web Of Science, and Cochrane databases, and a total of 5 randomized controlled trials and 11 cohort study trials were included. RESULTS: In terms of oncology and perioperative outcomes, there were no statistically significant differences between the radical resection group and the local resection group in terms of OS [HR = 0.99, 95%CI (0.85, 1.15), p = 0.858], DFS [HR = 1.01, 95%CI (0.64, 1.58), p = 0.967], distant metastasis rate [RR = 0.76, 95%CI (0.36,1.59), p = 0.464], and local recurrence rate [RR = 1.30, 95%CI (0.69, 2.47), p = 0.420]. However, there were significant differences in the outcomes of complications [RR = 0.49, 95% CI (0.33, 0.72), p < 0.001], length of hospital stays [WMD = - 5.13, 95%CI (- 6.22, - 4.05), p < 0.001], enterostomy [RR = 0.13, 95%CI (0.05, 0.37), p < 0.001], operative time [- 94.31, 95%CI (- 117.26, - 71.35), p < 0.001], and emotional functioning score [WMD = 2.34, 95% CI (0.94, 3.74), p < 0.001]. CONCLUSION: Local resection after neoadjuvant chemotherapy or chemoradiotherapy may be an effective alternative to radical surgery in patients with early and middle rectal cancer.

Oncologic outcomes of watch-and-wait strategy or surgery for low to intermediate rectal cancer in clinical complete remission after adjuvant chemotherapy: a systematic review and meta-analysis.

BACKGROUND: A watch-and-wait (WW) strategy or surgery for low to intermediate rectal cancer that has reached clinical complete remission (cCR) after neoadjuvant chemotherapy (nCRT) or total neoadjuvant therapy (TNT) has been widely used in the clinic, but both treatment strategies are controversial. OBJECTIVE: The aim of this study was to compare the oncologic outcomes of a watch-and-wait strategy or a surgical approach to treat rectal cancer in complete remission and to report the evidence-based clinical advantages of the two treatment strategies. METHODS: Seven national and international databases were searched for clinical trials comparing the watch-and-wait strategy with surgical treatment for oncological outcomes in patients with rectal cancer in clinical complete remission. RESULTS: In terms of oncological outcomes, there was no significant difference between the watch-and-wait strategy and surgical treatment in terms of overall survival (OS) (HR = 0.92, 95% CI (0.52, 1.64), P = 0.777), and subgroup analysis showed no significant difference in 5-year disease-free survival (5-year DFS) between WW and both local excision (LE) and radical surgery (RS) (HR = 1.76, 95% CI (0.97, 3.19), P = 0.279; HR = 1.98, 95% CI (0.95, 4.13), P = 0.164), in distant metastasis rate (RR = 1.12, 95% CI (0.73, 1.72), P = 0.593), mortality rate (RR = 1.62, 95% CI (0.93, 2.84), P = 0.09), and organ preservation rate (RR = 1.05, 95% CI (0.94, 1.17), P = 0.394) which were not statistically significant and on the outcome indicators of local recurrence rate (RR = 2.09, 95% CI (1.44, 3.03), P < 0.001) and stoma rate (RR = 0.35, 95% CI (0.20, 0.61), P < 0.001). There were significant differences between the WW group and the surgical treatment group. CONCLUSION: There were no differences in OS, 5-year DFS, distant metastasis, and mortality between the WW strategy group and the surgical treatment group. The WW strategy did not increase the risk of local recurrence compared with local resection but may be at greater risk of local recurrence compared with radical surgery, and the WW group was significantly better than the surgical group in terms of stoma rate; the WW strategy was evidently superior in preserving organ integrity compared to radical excision. Consequently, for patients who exhibit a profound inclination towards organ preservation and the evasion of stoma formation in the scenario of clinically complete remission of rectal cancer, the WW strategy can be contemplated as a pragmatic alternative to surgical interventions. It is, however, paramount to emphasize that the deployment of such a strategy should be meticulously undertaken within the ambit of a multidisciplinary team's management and within specialized centers dedicated to rectal cancer management.

Local resection versus radical resection for early-stage rectal cancer: a systematic review and meta-analysis.

PURPOSE: The optimal surgical approach for early-stage rectal cancer remains controversial. Radical resection is considered to be the gold standard for rectal cancer treatment. More and more studies show that local resection can replace traditional radical resection in the treatment of early rectal cancer. This research aimed to compare the efficacy of local excision and radical surgery for early-stage rectal cancer and report the evidence-based clinical advantages of both techniques. METHODS: The clinical trials comparing oncological and perioperative local and radical resection outcomes for early-stage rectal cancer were searched from 7 national and international databases. RESULTS: Finally, 3 randomized controlled trials and 14 cohort studies were included. In terms of oncology and perioperative outcomes, there were no statistically significant differences between the radical resection group and the local resection group in terms of OS (HR = 1.05, 95% CI (0.98, 1.13), DFS [HR = 1.18, 95% CI (0.93, 1.48), p = 0.168), distant metastasis rate (RR = 1.04, 95% CI (0.49, 2.20), p = 0.928), and mortality rate (RR = 1.52, 95% CI (0.80, 2.91), p = 0.200). However, there were significant differences in the outcomes of complications (RR = 2.85, 95% CI (2.07, 3.92), p < 0.001), length of hospital stays (WMD = 5.41, 95% CI (3.94, 6.87), p < 0.001), stoma rate (RR = 7.69, 95% CI (2.39, 24.77), p = 0.001), local recurrence rate (RR = 0.48, 95% CI (0.27, 0.86), p = 0.013), operative time (WMD = 74.68, 95% CI (68.00, 81.36), p < 0.001), blood loss (WMD = 156.36, 95% CI (95.48, 217.21, p < 0.001), and adverse events (RR = 1.59, 95% CI (1.05, 2.41), p = 0.027). CONCLUSION: Local excision may be a viable alternative to radical resection for early-stage rectal cancer, but higher quality clinical studies are needed to confirm this.

Prognostic value of inflammatory markers NLR, PLR, and LMR in gastric cancer patients treated with immune checkpoint inhibitors: a meta-analysis and systematic review.

Background: Immune checkpoint inhibitors (ICIs) represent a groundbreaking approach to cancer therapy. Inflammatory markers such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) have emerged as potential indicators strongly associated with tumor prognosis, albeit their prognostic significance remains contentious. The predictive value of NLR, PLR, LMR in patients with gastric cancer (GC) treated with ICIs has not been fully explored; therefore, we conducted a meta-analysis to examine the potential of inflammatory markers NLR, PLR, and LMR as survival predictors in this population. Methods: A comprehensive search was conducted across PubMed, Embase, Web of Science, and Cochrane databases, with the search cut-off date set as March 2024. Hazard ratios (HR) and their corresponding 95% confidence intervals (CI) were calculated to assess the prognostic significance of NLR, PLR, and LMR for both progression-free survival (PFS) and overall survival (OS). Results: Fifteen cohort studies involving 1336 gastric cancer patients were finally included in this meta-analysis. The results of the meta-analysis showed that high levels of NLR were associated with poorer OS and PFS in GC patients receiving ICIs, with combined HRs of OS [HR=2.01, 95%CI (1.72,2.34), P<0.01], and PFS PFS[HR=1.59, 95%CI (1.37,1.86), P<0.01], respectively; high levels of PLR were associated with poorer OS and PFS, and the combined HR was OS [HR=1.57, 95%CI (1.25,1.96), P<0.01], PFS [HR=1.52,95%CI (1.20, 1.94), P<0.01], respectively; and there was an association between elevated LMR and prolonged OS and PFS, and the combined HR was OS [HR=0.62, 95%CI (0.47,0.81), P<0.01], and PFS [HR=0.69, 95%CI (0.50,0.95), P<0.01]. Conclusion: In gastric cancer (GC) patients treated with immune checkpoint inhibitors (ICIs), elevated neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were associated with poorer overall survival (OS) and progression-free survival (PFS), while high lymphocyte-to-monocyte ratio (LMR) was linked to improved OS and PFS. Subgroup analyses suggested that NLR might be particularly pertinent to the prognosis of GC patients. In conclusion, the inflammatory markers NLR, PLR, and LMR serve as effective biomarkers for prognostic assessment in GC patients, offering valuable insights for therapeutic decision-making in the realm of GC immunotherapy. Prospective studies of high quality are eagerly awaited to validate these findings in the future. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/#myprospero, identifier CRD42024524321.

Preventive effects of chemical drugs on recurrence of colorectal adenomas: systematic review and Bayesian network meta-analysis.

BACKGROUND: The onset of colorectal adenomas (CRAs) is significantly associated with colorectal cancer. The preventive effects of chemical drugs on the recurrence of CRAs have been evaluated in a large number of randomized controlled trials (RCTs). However, there are still uncertainties about the relative effectiveness of such chemical drugs. METHODS: We searched relevant RCTs published in six databases up to February 2023. The quality of the included studies was assessed by using the Cochrane risk of bias assessment tool and Review Manager 5.4. Pairwise comparison and network meta-analysis (NMA) were conducted using RStudio to compare the effects of chemical drugs on the recurrence of CRAs. RESULTS: Forty-five high-quality RCTs were included. A total of 35 590 (test group: 20 822; control group: 14 768) subjects with a history of CRAs have been enrolled and randomized to receive placebo treatment or one of 24 interventions. Based on surface under the cumulative ranking values and NMA results, difluoromethylornithine (DFMO) + Sulindac significantly reduced the recurrence of CRAs, followed by berberine and nonsteroidal antiinflammatory drugs. CONCLUSION: DFMO + Sulindac is more effective in reducing the recurrence of CRAs but has a high risk of adverse events. Considering drug safety, tolerance, and compliance, berberine has a brighter prospect of clinical development. However, further studies are needed to verify our findings.

Clinical effects of chemical drugs, fecal microbiota transplantation, probiotics, dietary fiber, and acupuncture in the treatment of chronic functional constipation: a systematic review and network meta-analysis.

Currently, there are increasingly diverse treatment modalities for chronic functional constipation (CFC). This study aims to compare the relative efficacy and safety of chemical drugs, fecal microbiota transplantation (FMT), probiotics, dietary fiber, and acupuncture in the treatment of patients with CFC. We searched relevant randomized controlled trials (RCTs) published in five databases up to November 2023. Network meta-analysis (NMA) was carried out using R Studio 4.2.1. Cumulative ranking probability plots, assessed through the surface under the cumulative ranking (SUCRA), were employed to rank the included drugs for various outcome measures. We included a total of 45 RCT studies with 17 118 patients with CFC. From the SUCRA values and NMA results FMT showed the best utility in terms of clinical efficacy, Bristol stool form scale scores, patient assessment of constipation quality of life scores, and the treatment modality with the lowest ranked incidence of adverse effects was electroacupuncture. Subgroup analysis of the chemotherapy group showed that sodium A subgroup analysis of the chemical group showed that sodium picosulfate 10 mg had the highest clinical efficacy. FMT is more promising in the treatment of CFC and may be more effective in combination with the relatively safe treatment of acupuncture.

Therapeutic targets for endometriosis: Genome-wide Mendelian randomization and colocalization analyses.

BACKGROUND: Endometriosis (EM) greatly affects women's reproductive health, identifying new drug targets for EM is urgently needed. This study utilizes comprehensive genome-wide Mendelian randomization (MR) and colocalization analyses, using genomic data, to identify potential therapeutic approaches for EM. METHODS: Genome-wide cis-expression quantitative trait loci (cis-eQTL) data were obtained from GTEx V8, which included 838 participants across 49 tissues or cells, and the eQTLGen consortium, which included 31,684 participants. Genome-wide association analysis (GWAS) data for EM were sourced from the FinnGen study, which consisted of 8,288 cases and 68,969 controls, as well as the UK Biobank study, which included 1,496 cases and 359,698 controls. This study utilized MR analysis to assess the correlation between genes and the risk of EM. Subsequently, colocalization analysis was conducted to investigate potential shared causal variants between the identified genes and EM. RESULTS: After conducting MR and colocalization analyses, we identified a total of 13 genes that showed significant evidence of colocalization. These genes are considered promising therapeutic candidates for treating EM. Among them, inner membrane mitochondrial protein (IMMT), src kinase associated phosphoprotein 1 (SKAP1), lysine methyltransferase 5A (KMT5A), KLF transcription factor 12 (KLF12), GRB10 interacting GYF protein 1 (GIGYF1), Wnt family member 7A (WNT7A), Sad1 and UNC84 domain containing 1 (SUN1), and poly (ADP-ribose) polymerase family member 3 (PARP3) were found to have positive associations with the risk of EM. On the other hand, progestin and adipoQ receptor family member 8 (PAQR8), adaptor related protein complex 3 subunit mu 1 (AP3M1), surfeit 6 (SURF6), TUB bipartite transcription factor (TUB), and DNA polymerase delta interacting protein 2 (POLDIP2) were found to have inverse relationships with the risk of EM. CONCLUSIONS: Through genome-wide MR studies, a comprehensive set of genes associated with EM has been identified. Among them, IMMT, PAQR8, SKAP1, KMT5A, AP3M1, SURF6, KLF12, GIGYF1, TUB, WNT7A, SUN1, POLDIP2, and PARP3 show potential as therapeutic targets for EM treatment. Nonetheless, it is crucial to conduct further rigorous investigations to validate these prospects.

Efficacy and safety of standardized Ginkgo biloba extract as adjuvant therapy for intracerebral hemorrhage in China: A systematic review and meta-analysis.

Objective: The aim of this study was to systematically review the clinical efficacy and safety of standardized Ginkgo biloba extract (GBE) in the adjuvant treatment of intracerebral hemorrhage (ICH). Methods: Relevant RCTs on GBE as adjuvant therapy for ICH were searched in seven Chinese and English databases. Data extraction of the included literature was performed after duplicate checking and screening, and Stata 15.1 software was applied for data analysis. Results: With a total of 19 RCTs, the meta-analysis results showed that: Compared with conventional treatment alone, GBE combined with conventional treatment had a higher effective rate; NIHSS score and CSS score were lower; The residual hematoma was less. The volume of cerebral edema was smaller. ADL score was higher. MoCA score was higher. The serum levels of hs-CRP, TNF-α and IL-6 were lower; No significant difference was observed in the incidence of adverse reactions between conventional treatment alone and GBE combined with conventional treatment. Conclusion: This study suggests that GBE as adjuvant therapy for ICH has better efficacy and is relatively safe compared with conventional treatment alone. However, due to the quality and quantity of included studies, further validation by more methodologically rigorous and multi-center studies with larger sample sizes is needed.

Efficacy and Safety of Wuling Powder in the Treatment of Patients with Diabetic Nephropathy: A Systematic Review and Meta-Analysis.

Background: Wuling powder is a classical formula of traditional Chinese medicine (TCM), which is extensively applied to treat diabetic nephropathy (DN). However, there are no related reports on systematically evaluating the efficacy of Wuling powder in the treatment of DN. Targeted at this, this study was developed. Materials and Methods: This study systematically searched related articles from nine databases, including PubMed, Cochrane Library, Embase, Web of Science, China Knowledge Infrastructure (CNKI), China Biomedical CD-ROM (Sino Med), Wanfang database, Vipers database (VIP), and the China Clinical Trials Registry website. The randomized controlled trials (RCTs) involving Wuling Power to treat DN were included, which were published from the established data of the above databases to March 2022. In addition, the language of the studies was not restricted. Studies were meta-analyzed using the RevMan 5.4 software given in the Cochrane Collaboration Network. The treatment efficacy was measured using the weighted mean differences (WMD) and 95% confidence intervals (CI). Results: 24 studies were included for the final analysis. 24 h urine volume (WMD = 357.95; 95% CI [322.83, 393.06], p < 0.00001), 24 h urine protein quantification(24 h UPQ) (WMD = -1.30; 95% CI [-1.82, -0.78], p < 0.00001), serum creatinine (Scr) (WMD = -10.17; 95% CI [-11.13, -9.21], p < 0.00001), blood urea nitrogen (BUN) (WMD = -1.62; 95% CI [-2.30, -0.93], p < 0.00001), urinary albumin excretion rate (UAER) (WMD = -24.73; 95% CI [-35.46, -13.99], p < 0.00001), fasting blood glucose (FBG) (WMD = -0.63.95% CI [-0.97, -0.30], p = 0.002), glycated hemoglobin (WMD = -0.11; 95% CI [-0.30, 0.08], p=0.26), total cholesterol (TC) (WMD = -0.63; 95% CI [-1.23, -0.04], p=0.04), triglycerides (TG) (WMD = -0.46. 95% CI [-0.70, -0.23], p=0.0001), high-density lipoprotein cholesterol (HDL-C) (WMD = -0.32; 95% CI [0.03, 0.62], p=0.03), low-density lipoprotein cholesterol (LDL-C) (WMD = -0.57; 95% CI [-0.77, -0.37], p < 0.00001), and total effective rate (TER) (response ratio (RR) = 1.40; 95% CI [1.32, 1.48]; p < 0.00001) were concluded. The Wuling powder in the treatment of DN was statistically significant in all the above outcome indicators, and the efficacy of the treatment group was better than that of the control group. Conclusion: The results of this study provided evidence for the clinical application of Wuling powder to treat the DN, but it had to be further validated in higher-quality clinical studies.