Effect of RAS and BRAF mutations on peritoneal metastasis risk and cytoreductive surgery/hyperthermic intraperitoneal chemotherapy efficacy in colorectal cancer: A systematic review and meta-analysis.

BACKGROUND: Colorectal cancer (CRC) patients with peritoneal metastasis (CRC-PM) have a worse prognosis than those with liver and lung metastases. Cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) is an effective locoregional treatment for CRC-PM. To date, the prognostic analysis of CRS/HIPEC mostly focuses on clinical and pathological characteristics; however, genetic characteristics, such as RAS/BRAF mutation status, are not sufficient. This study aimed to systematically assess the correlation between RAS/BRAF status and PM risk, as well as the prognostic efficacy of CRS/HIPEC for CRC. METHOD: This study was written in accordance with the 2020 guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols. We searched PubMed, EMBASE, and the Cochrane library with the following keywords: "Peritoneal Neoplasms," "raf Kinases" and "ras Proteins". The fixed-effects model and inverse variance method were used for analysis. Odds ratios (OR) and 95 % confidence intervals (CI) were used to reflect the risk of PM associated with RAS/BRAF mutations. Hazard ratios (HR) and 95 % CI were used to evaluate the effects of RAS/BRAF mutations on the prognosis of CRS/HIPEC. RESULT: Eighteen articles included 5567 patients. In the risk analysis of PM, patients with BRAF mutation were more likely to have PM than those with wild-type BRAF (OR = 2.28, 95 % CI = 1.73-3.01, P < 0.001, I2 = 0 %). In contrast, there was no significant difference in the effect of RAS mutation and wild-type on PM of CRC (OR = 1.28, 95 % CI = 0.99-1.66, P = .06, I2 = 0 %). In a prognostic analysis of CRS/HIPEC, RAS mutation predicted poor overall survival (HR = 1.68, 95 % CI = 1.39-2.02, P < 0.001, I2 = 1 %) and disease-free survival (HR = 1.61, 95 % CI = 1.34-1.94, P < 0.001, I2 = 42 %). The results for BRAF mutation was consistent with the prognostic impact of RAS mutation's overall survival (HR = 2.57, 95 % CI = 1.93-3.44, P < 0.001, I2 = 0 %) and disease-free survival (HR = 1.90, 95 % CI = 1.40-2.56, P < 0.001, I2 = 82 %). CONCLUSION: BRAF mutation, rather than RAS mutation, was a high-risk factor for CRC-PM. And both BRAF and RAS mutations negatively affected the prognosis of CRS/HIPEC in CRC-PM patients. Our results could provide suggestions for the selection of comprehensive treatment for CRC-PM with RAS/BRAF mutations.

Prognostic value of circulating tumor cells associated with white blood cells in solid cancer: a systematic review and meta-analysis of 1471 patients with solid tumors.

BACKGROUND: The clinical relevance of circulating tumor cell-white blood cell (CTC-WBC) clusters in cancer prognosis is a subject of ongoing debate. This study aims to unravel their contentious predictive value for patient outcomes. METHODS: We conducted a comprehensive literature search of PubMed, Embase, and Cochrane Library up to December 2022. Eligible studies that reported survival outcomes and examined the presence of CTC-WBC clusters in solid tumor patients were included. Hazard ratios (HR) were pooled to assess the association between CTC-WBC clusters and overall survival (OS), as well as progression-free survival (PFS)/disease-free survival (DFS)/metastasis-free survival (MFS)/recurrence-free survival (RFS). Subgroup analyses were performed based on sampling time, treatment method, detection method, detection system, and cancer type. RESULTS: A total of 1471 patients from 10 studies were included in this meta-analysis. The presence of CTC-WBCs was assessed as a prognostic factor for overall survival and PFS/DFS/MFS/RFS. The pooled analysis demonstrated that the presence of CTC-WBC clusters was significantly associated with worse OS (HR = 2.44, 95% CI: 1.74-3.40, P < 0.001) and PFS/DFS/MFS/RFS (HR = 1.83, 95% CI: 1.49-2.24, P < 0.001). Subgroup analyses based on sampling time, treatment method, detection method, detection system, cancer type, and study type consistently supported these findings. Further analyses indicated that CTC-WBC clusters were associated with larger tumor size (OR = 2.65, 95% CI: 1.58-4.44, P < 0.001) and higher alpha-fetoprotein levels (OR = 2.52, 95% CI: 1.50-4.22, P < 0.001) in hepatocellular carcinoma. However, no significant association was found between CTC-WBC clusters and TNM stage, depth of tumor invasion, or lymph node metastasis in the overall analysis. CONCLUSIONS: CTC-WBC clusters are negative predictors for OS and PFS/DFS/MFS/RFS in patients with solid tumors. Monitoring CTC-WBC levels may provide valuable information for predicting disease progression and guiding treatment decisions.

Individualized Choice of Simultaneous Cholecystectomy in Patients with Gastric Cancer: A Systematic Review and Meta-analysis.

BACKGROUND: Patients undergoing gastrectomy for gastric cancer are more likely to develop gallstones than the general population. Prophylactic cholecystectomy remains controversial. METHODS: Studies from 2000-2022 were systematically searched in the PubMed, EMBASE, and Cochrane Library databases. The search included simultaneous cholecystectomy or risk factors for gallstone formation with gastrectomy alone. Major prognostic factors included complications and mortality, and risk factor analyses included age, sex, TNM stage, gastrectomy type, lymph node dissection, diabetes, and duodenal exclusion. Random effects regression models were used to analyze risk estimates and data were presented as odds ratios (ORs) with corresponding 95% confidence intervals (CIs). RESULTS: There were no significant differences in postoperative morbidity (OR 1.12, 95% CI 0.90-1.39; p = 0.33, I2 = 11%) and mortality (OR 1.23, 95% CI 0.62-2.43; p = 0.56, I2 = 0%) between gastrectomy alone and simultaneous cholecystectomy. Older age (OR 1.48, 95% CI 1.36-1.59; p < 0.001, I2 = 59%), male sex (OR 1.38, 95% CI 1.10-1.71; p = 0.004, I2 = 77%), total gastrectomy (OR 1.50, 95% CI 1.25-1.81; p < 0.001, I2 = 72%), diabetes mellitus (OR 1.38, 95% CI 1.17-1.63; p < 0.001, I2 = 8%), and duodenal exclusion (OR 1.77, 95% CI 1.47-2.15; p < 0.001, I2 = 30%) were risk factors for cholecystolithiasis. CONCLUSIONS: Simultaneous cholecystectomy did not increase the incidence of postoperative complications or mortality. Older age, male sex, total gastrectomy, duodenal exclusion, and diabetes were risk factors for gallstone development after gastrectomy.

The negative impact of opioids on cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis.

PURPOSE: As one of the most effective analgesics, opioids are essential for patients with cancer-related pain, even in the context of the opioid abuse crisis. The current meta-analysis aimed to identify whether concomitant exposure to opioids can affect the efficacy of ICIs and lead to a worse prognosis. METHODS: PubMed, Embase, and the Cochrane Library were searched based on the PRISMA checklist, through April 2022, for the following terms: ("opioids" OR "concomitant medication") AND ("Neoplasm" OR "Carcinoma" OR "Cancer" OR "Tumor") AND ("Immunotherapy" OR "Immune Checkpoint Inhibitor" OR "PD-L1 Inhibitor" OR "PD-1 Inhibitor" OR "CTLA-4 Inhibitor"). The outcomes considered were overall survival (OS) and progression-free survival (PFS) calculated using the random-effects or fixed-effects model. RESULTS: After screening 531 studies, a total of 7 articles involving 2690 patients were eligible for quantitative analysis. The use of opioids was negatively correlated with OS (HR 1.75, 95%CI 1.32-2.31, P < 0.001; I2 = 81%, P < 0.001) and significantly reduced the PFS (HR 1.61, 95%CI 1.41-1.83, P < 0.001; I2 = 0%, P = 0.63) of patients treated with ICIs. Similar results were obtained in each subgroup analysis. While NSAIDs could lead to poor OS (HR 1.25, 95% CI 1.03-1.51, P = 0.02; I2 = 0%, P = 0.60) but not PFS (HR 1.11, 95% CI = 0.89-1.39, P = 0.36) for ICIs patients. And sensitivity analyses confirmed the reliability of the results. CONCLUSION: Opioids significantly reduced OS and PFS in patients receiving ICI therapy. Thus, the use of different types of opioids should be considered with caution, and it is necessary to actively develop alternative treatments.

Efficacy and factors affecting the choice of enucleation and liver resection for giant hemangioma: a retrospective propensity score-matched study.

BACKGROUND: Liver resection (LR) and enucleation (EN) are the main surgical treatment for giant hepatic hemangioma (HH), but how to choose the type of surgery is still controversial. This study aimed to explore the efficacy and the factors affecting the choice of open procedure for HH. METHODS: The data for patients with pathologically confirmed HH who underwent open surgery from April 2014 to August 2020 were analyzed retrospectively. Univariate and multivariate analyses with logistic regression were performed to disclose the factors associated with the choice of EN or LR. Propensity score matching (PSM) analysis was used to compare the efficacy of the two procedures. RESULTS: A total of 163 and 110 patients were enrolled in the EN and LR groups. Following 1:1 matching by PSM analysis, 66 patients were selected from each group. Centrally located lesions (OR: 0.131, 95% CI 0.070-0.244), tumors size > 12.1 cm (OR: 0.226, 95% CI 0.116-0.439) and multiple tumors (OR: 1.860, 95% CI 1.003-3.449) were independent factors affecting the choice of EN. There was no significant difference in the median operation time (156 vs. 195 min, P = 0.156), median blood loss (200 vs. 220 ml, P = 0.423), blood transfusion rate (33.3% vs. 33.3%, P = 1.000), mean postoperative feeding (3.1 vs. 3.3 d, P = 0.460), mean postoperative hospital stay (9.5 vs. 9.0 d, P = 0.206), or the major complication rates between the two groups. CONCLUSIONS: Peripherally located lesions, tumors size ≤ 12.1 cm and multiple tumors were more inclined to receive EN. There was no significant difference in the efficacy of EN or LR.