Effect of postoperative intermittent boluses of subcostal quadratus lumborum block on pulmonary function recovery and analgesia after gastrectomy: a randomized controlled clinical trial.

BACKGROUND: Following the gastrectomy, the reduction in pulmonary function is partly attributed to postoperative pain. Subcostal quadratus lumborum block (QLB) has recently emerged as a promising component in multimodal analgesia. We aimed to assess the impact of intermittent boluses of subcostal QLB on pulmonary function recovery and analgesic efficacy after gastrectomy. METHODS: Sixty patients scheduled for gastrectomy were randomly assigned to either control group (multimodal analgesia) or intervention group (intermittent boluses of subcostal QLB plus multimodal analgesia). Two primary outcomes included the preservation of forced expiratory volume in the first second (FEV1) and the pain scores (0-10 cm visual analog score) on coughing 24 h postoperatively. We assessed the pulmonary function parameters, pain score, morphine consumption and number of rescue analgesia at a 24-h interval up to 72 h (Day1, Day2, Day3 respectively) as secondary outcomes. RESULTS: 59 patients were analyzed in a modified intention-to-treat set. The preservation of FEV1 (median difference: 4.0%, 97.5% CI: -5.7 to 14.9, P = 0.332) and pain scores on coughing (mean difference: 0.0 cm, 97.5% CI: -1.1 to 1.2, P = 0.924) did not differ significantly between two groups. In the intervention group, the recovery of forced vital capacity (FVC) was faster 72 h after surgery (interaction effect of group*(Day3-Day0): estimated effect (ß) =0.30 L, standard error (SE) =0.13, P = 0.025), pain scores at rest were lower in the first 3 days (interaction effect of group*(Day1-Day0): ß = - 0.8 cm, SE = 0.4, P = 0.035; interaction effect of group*(Day2-Day0): ß = - 1.0 cm, SE = 0.4, P = 0.014; and interaction effect of group*(Day3-Day0): ß = - 1.0 cm, SE = 0.4, P values = 0.009 respectively), intravenous morphine consumption was lower during 0-24 h (median difference: -3 mg, 95% CI -6 to -1, P = 0.014) and in total 72 h (median difference: -5 mg, 95% CI -10 to -1, P = 0.019), and the numbers of rescue analgesia was fewer during 24-48 h (median difference: 0, 95% CI 0 to 0, P = 0.043). Other outcomes didn't show statistical differences. CONCLUSION: Postoperative intermittent boluses of subcostal QLB did not confer advantages in terms of the preservation of FEV1 or pain scores on coughing 24 h after gastrectomy. However, notable effects were observed in analgesia at rest and FVC recovery.

How to Omit the Potential Pitfalls in Distal Radial Access: Lessons From Cadaveric and CTA Analysis.

OBJECTIVES: To verify the anatomical basis, ideal puncture sites, and potential pitfalls of the distal radial artery (dRA) in the anatomical snuffbox region for distal radial access (dTRA). MATERIALS AND METHODS: Overall, 26 formalin-fixed upper limbs and computed tomography angiography (CTA) of the upper limbs of 168 consecutive patients were studied. Cadaveric dissection and dRA 3D reconstruction were used to evaluate the dRA route for dTRA. The puncture sites, dRA diameter, and angle of the dRA and tendons of the extensor pollicis brevis were also measured in the patients and cadavers. RESULTS: The cadaver dissection provided more insights than did the dRA 3D reconstruction. However, preoperative evaluation had better diagnostic accuracy (p=0.024). Puncture sites 1 and 3 had a high success rate (63.2% possible success rate, 191/302). The DISFAVOR theory was put forward, in which 8 types of potential pitfalls that may interrupt puncture procedure or lead to a surgical failure were observed, including occlusion, stenosis, tortuosity, arteriovenous fistula, angioma, different radial artery (RA) ramifications, radial veins, and cephalic veins. The mean diameter of dRA based on cadaver dissection and CTA was 2.53 (SD=0.73) and 2.63 (SD=0.69) mm, respectively. Furthermore, the minimum distance from the outer layer of dRA to the skin was 5.71 (SD=2.0) mm based on CTA. The angle between the dRA and tendons of extensor pollicis brevis (TEPB) based on cadaver dissection and CTA was 58.0° (SD=21.5°) and 51.8° (SD=16.6°), respectively. CONCLUSIONS: Puncture sites 1 and 3 were more suitable for the dTRA, and we put forward the DISFAVOR theory to summarize the 8 types of potential pitfalls during the use of dTRA.

Assessment of Systemic Inflammation and Nutritional Indicators in Predicting Recurrence-Free Survival After Surgical Resection of Gastrointestinal Stromal Tumors.

BACKGROUND: Recent studies have shown that the systemic inflammation and nutritional indicators are prognostic for a variety of malignancies. However, only limited data have so far demonstrated their usefulness in gastrointestinal mesenchymal tumors (GIST). METHODS: We retrospectively analyzed the data of GIST patients who underwent radical surgery in Beijing hospital from October 2004 to July 2018. The area under the receiver operating characteristic curve (AUC) was used to compare several commonly used inflammatory and nutritional indicators. The indicators with largest AUC were further analysis. Optimal cut-off values of those indicators in predicting recurrence-free survival (RFS) were determined. Kaplan-Meier curve and the time-dependent receiver operating characteristic (ROC) curve were used to assess the prognostic values. We then used univariate and multivariate Cox regression analyses to identify prognostic factors that were associated with RFS. RESULTS: In total, 160 patients who underwent surgery for GIST were included in the study. The median survival time was 34.5 months, with 1-, 3-, and 5-year RFS rates of 96.1%, 84.7%, and 80.8%, respectively. The inflammatory and nutritional indicators with largest AUC were Systemic immunoinflammatory Index (SII) and Geriatric Nutrition Risk Index (GNRI), reached 0.650 and 0.713, respectively. The optimal cutoff of GNRI and SII were 98.3, and 820.0, respectively. Univariate analysis showed that GNRI, SII, KI67, surgery method, tumor location, tumor size, and mitotic index were all significant prognostic indicators of RFS. After multivariate Cox analysis, independent prognostic factors for RFS in GIST included tumor location, mitotic index, tumor size, and GNRI (HR=2.802,95% CI: 1.045 to 7.515, p = 0.041). Besides, SII also tended to be associated with RFS (HR = 2.970, 95% CI: 0.946 to 9.326, p = 0.062). CONCLUSIONS: High GNRI is an independent prognostic factor for RFS in GIST, while SII can be considered as a prognostic factor. GNRI and SII can be used as tools to evaluate the prognosis of patients before surgery, helping doctors to better treat high-risk patients.

Preoperative C-Reactive Protein/Albumin Ratio is a Prognostic Indicator for Survival in Surgically Treated Gastrointestinal Stromal Tumors: A Retrospective Cohort Study.

BACKGROUND: Systemic inflammation and malnutrition may promote tumor progression. C-reactive protein/albumin ratio (CAR) is linked to the poor long-term survival of several malignant tumors. PURPOSE: To explore the predictive value of CAR in gastrointestinal stromal tumors (GISTs). METHODS: A retrospective study was conducted on 325 patients with primary GIST surgically treated with curative intent from 2009 to 2018. The cut-off point of CAR was set using X-tile software. Kaplan-Meier method and multivariate Cox regression model were used to study the prognostic value of CAR. The time-dependent receiver operating characteristic curve (tROC) was drawn, and the prognostic accuracy of CAR, Glasgow prognostic score (GPS), and National Institute of Health (NIH) risk classification was compared by the area under the curve (AUC). RESULTS: The best cut-off point of CAR was 0.55. Increased CAR was associated with the location of the lower digestive tract, larger tumor size, higher mitotic index, higher NIH risk classification, lower ALB, higher CRP, and higher GPS (all p<0.05). Multivariable analysis revealed that CAR (hazard ratio [HR] 2.598, 95% confidence interval [CI] 1.385-4.874; p=0.003) was an independent predictor of overall survival. Additionally, the AUC of CAR was lower than that of NIH risk classification at 2 years (0.601 vs. 0.775, p=0.002) and 5 years (0.629 vs 0.735, p=0.069). However, the AUC of NIH risk classification significantly increased (2-year OS 0.801, p=0.251; 5-year OS 0.777, p=0.011) when combined with CAR. CONCLUSION: CAR is a new independent predictor of poor survival in patients with GIST. CAR combined with NIH risk classification can effectively improve the performance of prognosis prediction.

Fibrinogen/Albumin Ratio Index Is an Independent Prognosis Predictor of Recurrence-Free Survival in Patients After Surgical Resection of Gastrointestinal Stromal Tumors.

Background: Nutritional status, systemic inflammation, and coagulation mechanism are closely related to tumor progression. Herein, we examined the role of fibrinogen-to-albumin ratio index (FARI) in the prognosis of gastrointestinal stromal tumors (GISTs) and developed a novel nomogram predicting recurrence-free survival (RFS). Methods: We retrospectively analyzed data from 357 GIST patients admitted at the gastrointestinal surgery of the Beijing Hospital from January 2008 to January 2018 and underwent curative resection. FARI was calculated as fibrinogen level (g/L) /albumin level (g/L). The cutoff point of FARI was set using the point with the largest Youden index on the receiver operating characteristic curve with the 5-years recurrence-free survival as an endpoint. We used the Kaplan-Meier approach and multivariable Cox regression model to study the impact of FARI on recurrence-free survival. Finally, we developed a nomogram based on tumor size, location, mitotic index, and FARI to predict RFS. The nomogram was assessed by calculating concordance probabilities and testing calibration of predicted RFS with observed RFS. Concordance probabilities were also compared with the National Institute of Health (NIH) risk classification system. Results: The ROC curve revealed that the best cutoff point of the FARI was set as 0.08. The patients were classified into the FARI-high (≥0.08) and FARI-low (<0.08) groups. FARI was significantly associated with age, size of the tumor, NIH risk category, and Mitotic Index (all P < 0.05). FARI was weakly associated with NLR and PLR. FARI and PNI had a weak negative association. Multivariate analysis showed that the NIH risk category and FARI were independent prognostic predictors for worse outcomes concerning RFS in GIST patients. In the high-risk subgroup, patients with low FARI also had a more prolonged RFS than patients with high FARI (P < 0.05). The nomogram had a concordance probability of 0.802 (SE 0.025). Nomogram predictions were well-calibrated. Concordance probabilities of the nomogram were better than NIH risk classification system [0.802 [0.025] vs. 0.737 [0.024], p < 0.01]. Conclusion: We established that preoperative FARI is a novel serum biomarker to predict the prognosis after surgical resection of GISTs. The nomogram incorporating FARI could be used to help the decision-making of clinical treatment.

GOLPH3 inhibition reverses oxaliplatin resistance of colon cancer cells via suppression of PI3K/AKT/mTOR pathway.

OBJECTIVE: To explore whether GOLPH3 regulated oxaliplatin (L-OHP) resistance of colon cancer cells via PI3K/AKT/mTOR pathway. METHODS: HCT116/L-OHP cells were divided into Blank, Control/GOLPH3 shRNA, BEZ235 (a PI3K/AKT/mTOR inhibitor), and GOLPH3 + BEZ235 groups followed by the detection with MTT, soft agar colony formation, flow cytometry and TUNEL assays. Mice bearing HCT116/L-OHP xenografts were randomized into Control, L-OHP, NC/GOLPH3 shRNA, L-OHP + NC/GOLPH3 shRNA groups. The expressions of Ki67, Caspase-3, and PI3K/AKT/mTOR pathway proteins were examined by immunohistochemistry. RESULTS: HCT116/L-OHP cells had increased GOLPH3 expression compared to HCT116 cells, which positively regulated PI3K/AKT/mTOR pathway in HCT116/L-OHP cells. BEZ235 declined IC50 of HCT116/L-OHP cells to L-OHP, decreased the expressions of ABCB1, ABCC1, ABCG2, ATP7A, ATP7B, MATE1, p-gp, MRP1 and BCRP, induced cell apoptosis, reduced cell proliferation, and arrested cells at G0/G1, which was reversed by GOLPH3 overexpression. L-OHP and GOLPH3 shRNA decreased tumor volume and reduced expression of Ki67 in tumor tissues with the increased Caspase-3. Meanwhile, the combined treatment had the better treatment effect. CONCLUSION: GOLPH3 inhibition reduced proliferation and promoted apoptosis of HCT116/L-OHP cells, and also reversed the L-OHP resistance of HCT116/L-OHP, which may be associated with the suppression of P13K/AKT/mTOR pathway.

Prognostic significance of preoperative plasma fibrinogen levels in primary gastrointestinal stromal tumours: a retrospective cohort study.

BACKGROUND: Improved prediction of prognosis for gastrointestinal stromal tumours (GISTs) has become increasingly important since the introduction of targeted therapy. Here, we aimed to evaluate the prognostic significance of preoperative plasma fibrinogen (Fib) levels in patients with primary GISTs and to analyse their correlations with clinicopathological characteristics. METHODS: A total of 201 previously untreated patients with primary GISTs who had undergone radical surgery at our institution between October 2004 and July 2018 were enrolled. The optimal cut-off value for Fib levels was calculated using time-dependent receiver-operating characteristic curve analysis. RFS, the primary endpoint, was calculated by the Kaplan-Meier method and compared by the log-rank test. Univariate and multivariate Cox regression models were calculated. RESULTS: High preoperative plasma Fib levels were detected as an independent adverse prognostic factor (p = 0.008, hazard ratio 3.136, 95% CI 1.356‒7.256). Furthermore, high preoperative plasma Fib levels also indicated a poor prognosis within the modified National Institutes of Health (mNIH) high-risk subgroup (p = 0.041). In addition, preoperative plasma Fib levels showed a positive correlation with several prognostic factors and even a linear relationship with tumour size (Spearman correlation coefficient [r] = 0.411, p < 0.001). CONCLUSIONS: Our results suggest that high preoperative plasma Fib levels may indicate a poor prognosis in patients with primary GISTs. As a cost-effective biomarker, preoperative assessment of plasma Fib levels may help to further risk stratify patients with mNIH high-risk GISTs and instruct the application of targeted therapy.

MicroRNA-423-5p inhibits colon cancer growth by promoting caspase-dependent apoptosis.

Plasma microRNA (miR)-423-5p is a potential biomarker for the detection of colon cancer. However, the expression and biological role of miR-423-5p in colon tumorigenesis remains unclear. In the current study, reverse transcription-quantitative polymerase chain reaction was used to determine miR-423-5p expression in malignant colon tissues and plasma from patients with colon cancer. Cell viability, colony formation and apoptosis assays, as well as western blotting, were performed to investigate the biological role and regulatory mechanisms of miR-423-5p in colon cancer. The results demonstrated that miR-423-5p expression was downregulated in tumor tissues and plasma from patients with colon cancer, as well as in colon cancer cell lines. Furthermore, overexpression of miR-423-5p promoted colon cancer cell apoptosis and resulted in the inhibition of cell proliferation and colony formation. Mechanistically, miR-423-5p induced the expression of caspases 3, 8 and 9, as well as p53 in colon cancer. The effect of z-VAD treatment indicated that the miR-423-5p-mediated colon cancer cell apoptosis is caspase-dependent. These results suggest that miR-423-5p is a tumor suppressor in colon cancer and a potential diagnostic target to enable the early detection of colon cancer.

Bioinformatic Analysis of GLI1 and Related Signaling Pathways in Chemosensitivity of Gastric Cancer.

BACKGROUND This study assessed the prognostic value of GLI1 in gastric cancer and analyzed the possible GLI1-related signaling network in chemosensitivity. MATERIAL AND METHODS Bioinformatic data mining was performed by using data in the TCGA-Stomach Cancer (TCGA-STAD) and the Kaplan-Meier plotter. GLI1 co-expressed genes in TCGA-STAD were subjected to KEGG pathway analysis. The genes enriched in the KEGG pathways were further subjected to Protein-Protein Interaction (PPI) analysis. RESULTS In TCGA-STAD, high GLI1 gene/exon expression was associated with significantly worse survival (p=0.016 and 0.0023 respectively). In the Kaplan-Meier plotter, high GLI1 expression was associated with unfavorable overall survival (OS) (HR: 1.68, 95%CI: 1.42-2, p<0.0001) and first progression-free survival (FPS) (HR: 1.72, 95%CI: 1.4-2.11, p<0.0001). In TCGA-STAD, 600 GLI1 co-expressed genes were identified (absolute Pearson's r ≥0.5). The most significant pathways were pathways in cancer (p=230.0E-12) and the Hedgehog signaling pathway (p=6.9E-9). PI3K-AKT pathway (p=17.0E-9) has the largest proportion of gene enrichment. Some GLI1 co-expressed genes in the PI3K-AKT pathway are central nodes in the PPI network and also play important roles in chemosensitivity of gastric cancer. Nevertheless, the mechanisms underlying their co-expression are still largely unexplored. CONCLUSIONS High GLI1 expression is associated with unfavorable OS and FPS in patients with gastric cancer. As a member of the Hedgehog signaling pathway, GLI1 co-expressed genes are also largely enriched in PI3K/AKT pathway in gastric cancer, which is closely related to chemoresistance. The underlying mechanisms are still largely unexplored and need further study.

Preoperative Prognostic Nutritional Index Correlates with Severe Complications and Poor Survival in Patients with Colorectal Cancer Undergoing Curative Laparoscopic Surgery: A Retrospective Study in a Single Chinese Institution.

The prognostic nutritional index (PNI) has been correlated with long-term outcomes in cancer patients. However, the relationship between PNI, the postoperative complications, and long-term outcomes in patients with colorectal cancer (CRC) undergoing curative laparoscopic surgery has not been fully investigated. This retrospective study was conducted in the Beijing Hospital between January 2009 and January 2012. A total of 228 patients diagnosed with primary CRC undergoing curative laparoscopic surgery in the center were analyzed. The last follow-up date was December 2015. The associations of the PNI status with postoperative outcomes were examined using univariate and multivariate analyses. The optimal cutoff value of the preoperative PNI was set at 44.55 using the receiver operating characteristic curve. The patients were classified into PNI-high (≥44.55) and PNI-low groups (<44.55). The patients in the PNI-low group were more likely to have increased levels of tumor markers such as carcinoembryonic antigen and carbohydrate antigen 19-9, aggressive histological features, advanced tumor-nodes-metastasis (TNM) stages (all P < 0.05). Multivariate analyses revealed PNI<44.55 as an independent factor associated with the incidence of severe postoperative complications and overall survival. In conclusion, for patients with CRC undergoing curative laparoscopic surgery, PNI is a valuable biomarker in preoperative estimation as well as prognosis prediction.

[Predictive value of Glasgow prognostic score in patients with colorectal cancer undergoing laparoscopic radical resection].

OBJECTIVE: To investigate the predictive value of preoperative Glasgow prognostic score (GPS) for the postoperative complications and survival in patients with colorectal cancer (CRC) undergoing laparoscopic radical resection. METHODS: This retrospective study was conducted in the Beijing Hospital between January 2009 and January 2012. A total of 228 patients with primary CRC undergoing laparoscopic radical resection were analyzed. The GPS was constructed based on routine preoperative blood tests of C-reactive protein and serum albumin. The patients were classified into three groups according to GPS (GPS 0, 1, 2 groups). Survival curves were described by the Kaplan-Meier method and compared by the Log-rank test. The univariate and multivariate analyses were performed with the Cox proportional hazard model to identify the influence of GPS on prognosis in patients with CRC undergoing laparoscopic radical resection. RESULTS: Preoperative CRP level was increased in 48 cases (21.1%), and preoperative serum albumin level was decreased in 104 cases (45.6%) in the whole group. These 228 patients were classified into 99, 105 and 24 patients in GPS 0, 1, 2 group respectively. GPS was significantly associated with age, preoperative body mass index (BMI), carcinoembryonic antigen (CEA), CA19-9, tumor location, tumor differentiation and TNM stage (all P<0.05). Postoperative complication rates of GPS 0, 1, 2 group were 6.1%, 14.3% and 70.8% respectively (χ2=59.147, P=0.000). Serious postoperative complication rates were 3.0%, 6.7% and 58.3% respectively (χ2=65.807, P=0.000). Univariate and multivariate analyses revealed that GPS was an independent risk factor of postoperative complications(HR=21.611, 95%CI: 5.936-78.681, P=0.000) and severe complications (HR=35.833, 95%CI: 7.364-174.355, P = 0.000). The 5-year survival rate was 50% and the average total survival time was 58.2 (95% CI: 54.6-61.7) months in the whole group. The median overall survival time in GPS 0, 1, 2 group was 74.6(95%CI: 70.4-78.7) months, 49.8(95%CI: 45.2-54.4) months and 27.8 (95%CI: 21.8-33.8) months respectively(χ2=98.425, P=0.000). The median disease-free survival time was 73.9(95%CI: 69.2-78.7) months, 47.4 (95% CI: 41.6-53.1) months and 19.9 (95%CI: 14.8-25.0) months respectively (χ2=91.305, P=0.000). GPS was an independent risk factor of disease-free survival (HR=4.840, 95%CI: 2.413-9.709, P=0.000) and overall survival (HR=6.267, 95%CI: 3.073-12.784, P=0.000). CONCLUSIONS: GPS can be used as an effective predictor of the prognosis for patients with CRC undergoing laparoscopic radical surgery. Higher GPS suggests more postoperative complications and worse prognosis.

Clinical effect of DAPK promoter methylation in gastric cancer: A systematic meta-analysis.

BACKGROUND: The loss of death-associated protein kinase (DAPK) gene expression through promoter methylation is involved in many tumors. However, the relationship between DAPK promoter methylation and clinicopathological features of gastric cancer (GC) remains to be done. Therefore, we performed a meta-analysis to assess the role of DAPK promoter methylation in GC. METHODS: Literature databases were searched to retrieve eligible studies. The pooled odds ratios (ORs) with its 95% confidence intervals (CIs) were calculated using the Stata 12.0 software. RESULTS: Final 22 available studies with 1606 GC patients and 1508 nonmalignant controls were analyzed. A significant correlation was found between DAPK promoter methylation and GC (OR = 3.23, 95% CI = 1.70-6.14, P < 0.001), but we did not find any significant association in Caucasian population, and in blood samples in subgroup analyses. DAPK promoter methylation was associated with tumor stage and lymph node status (OR = 0.69, 95% CI = 0.49-0.96, P = 0.03; OR = 1.50, 95% CI = 1.12-2.01, P = 0.007; respectively). However, we did not find that DAPK promoter methylation was associated with gender status and tumor histology. CONCLUSION: Our findings suggested that DAPK promoter methylation may play a key role in the carcinogenesis and progression of GC. In addition, methylated DAPK was a susceptible gene for Asian population. However, more studies with larger subjects should be done to further evaluate the effect of DAPK promoter methylation in GC patients, especially in blood and Caucasian population subgroup.

[Comparative analysis of postoperative complications on elderly colorectal cancer patients over 65 years with and without comorbid cardiovascular diseases].

OBJECTIVE: To investigate the risk of postoperative complications in elderly colorectal cancer patients over 65 years with comorbid cardiovascular diseases. METHODS: A total of 381 elderly colorectal cancer patients over 65 years were pathologically diagnosed as colorectal adenocarcinoma and underwent the first surgery in Beijing Hospital during January 2013 and December 2014. Patients were divided into comorbid cardiovascular disease group (258 cases) and non-cardiovascular disease group (123 cases) according to the existence of comorbid cardiovascular disease. The morbidity of postoperative complication was compared between two groups. RESULTS: There was no significant difference in the morbidity of postoperative complication between two groups [27.9%(72/258) vs. 29.3%(36/123), P>0.05]. According to the Clavien-Dindo classification of postoperative complications, the morbidities of complication at all levels between two groups were not significantly different(all P>0.05). But in terms of cardiovascular complications, the morbidity of comorbid cardiovascular disease group was significantly higher than that of non-cardiovascular disease group [7.4%(19/258) vs. 0.8%(1/123), χ2=6.678, P=0.010], while no significant differences in pulmonary and abdominal complications were found between two groups(all P>0.05). The morbidities of other complications (deep vein thrombosis, urinary tract infection and renal complications, etc.) of comorbid cardiovascular disease group were lower than those in non-cardiovascular disease group [2.7%(7/258) vs. 8.1%(10/123), χ2=5.733, P=0.017]. Different types of cardiovascular diseases, different levels of cardiac risk index and American Society of Anesthesiologists(ASA) rating were not significantly related to the patient's occurrence of postoperative complications(all P>0.05). CONCLUSIONS: Surgery treatment for elderly colorectal cancer patients over 65 years with comorbid cardiovascular diseases is safe. However, strict cardiovascular monitoring should be performed and necessary measures should be carried out in time.