ABSTRACT
Background: Selecting the appropriate preoperative neoadjuvant chemotherapy (NACT) regimen for patients with advanced gastric cancer (GC) is critical to effective treatment. The aim of this study was to develop nomograms based on pretherapeutic computed tomography (CT) features to predict response to NACT with S-1 and oxaliplatin (SOX) or that with docetaxel and SOX (DOS) in patients with advanced GC. Methods: This study enrolled 311 consecutive patients with confirmed advanced GC undergoing contrast-enhanced CT before and after the three cycles of NACT with DOS (n=152) or SOX (n=159), who were randomized into a training cohort (TC) (NACT with DOS: n=111; NACT with SOX: n=120) and validation cohort (VC) (NACT with DOS: n=41; NACT with SOX: n=39). The objective response rate (ORR) was used to evaluate the response to NACT. In the TC, ORR was compared between the DOS and SOX regimens, and independent predictors including CT features and tumor differentiation were determined by univariate and binary logistic regression analyses. Individual nomograms were constructed for the SOX and DOS regimens in the TC, and the predictive accuracy was validated in the VC. Results: After NACT, the percentage of ORR was higher in patients receiving DOS than in those receiving SOX in TC (P value <0.05). The independent predictors after DOS and SOX were pretherapeutic cT stage [odds ratio (OR) =7.364; OR =8.848], cN stage (OR =1.027; OR =1.345), degree of differentiation (OR =7.127; OR =7.835), and gross tumor volume (OR =8.960; OR =8.161) (all P values <0.05). The concordance indexes of the individual nomograms developed using these predictors were 0.940 and 0.932 after DOS or SOX in the TC, respectively, which was validated by calibration plots with a slope close to 45° in the TC and VC. Conclusions: Despite there being a superior response to DOS compared with SOX, nomograms for predicting response to both NACT regimens were similar, with each demonstrating good predictive performance.
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Aims: This study aimed to synthesize the evidence of the comparative effectiveness and safety of Ophiocordyceps sinensis (OS) preparations combined with renin-angiotensin system inhibitors (RASi) for diabetic kidney disease (DKD). Methods: Eight databases were searched from their inception to May 2023. Systematic reviews (SRs) of OS preparations combined with RASi for DKD were identified. Randomized controlled trials (RCTs) from the included SRs and additional searching were performed for data pooling. Cochrane risk-of-bias 2 (RoB 2) tool and AMSTAR 2 were used to evaluate the methodological quality of RCTs and SRs, respectively. A Bayesian network meta-analysis was performed to compare the add-on effect and safety of OS preparations for DKD. The certainty of evidence was graded using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Results: Fourteen SRs were included, whose methodological quality was assessed as high (1/14) or critically low (13/14). After combining additional searching, 157 RCTs were included, involving 13,143 participants. The quality of the RCTs showed some concerns (155/157) or high risk (2/157). Jinshuibao capsules and tablets, Bailing capsules and tablets, and Zhiling capsules were evaluated. Compared to RASi, adding either of the OS capsular preparations resulted in a decreased 24-h urinary total protein levels. OS preparations ranked differently in each outcome. Jinshuibao capsules plus RASi were beneficial in reducing urinary protein, serum creatinine, serum urea nitrogen, and blood glucose levels, with moderate-certainty evidence. No serious adverse events were observed after adding OS to RASi. Conclusion: Combining OS capsular preparations with RASi appeared to be associated with decreased urinary total protein levels in DKD patients. Further high-quality studies are needed to confirm. Systematic Review Registration: INPASY202350066.
ABSTRACT
It is important to accurately determine the resectability of thoracic esophageal squamous cell carcinoma (ESCC) for treatment decision-making. Previous studies have revealed that the CT-derived gross tumor volume (GTV) is associated with the staging of ESCC. The present study aimed to explore whether the anatomical distribution-based GTV of non-distant metastatic thoracic ESCC measured using multidetector computed tomography (MDCT) could quantitatively determine the resectability. For this purpose, 473 consecutive patients with biopsy-confirmed non-distant metastatic thoracic ESCC who underwent contrast-enhanced CT were randomly divided into a training cohort (TC; 376 patients) and validation cohort (VC; 97 patients). GTV was retrospectively measured using MDCT. Univariate and multivariate analyses were performed to identify the determinants of the resectability of ESCC in the TC. Receiver operating characteristic (ROC) analysis was performed to clarify whether anatomical distribution-based GTV could help quantitatively determinate resectability. Unweighted Cohen's Kappa tests in VC were used to assess the performance of the previous models. Univariate analysis demonstrated that sex, anatomic distribution, cT stage, cN stage and GTV were related to the resectability of ESCC in the TC (all P<0.05). Multivariate analysis revealed that GTV [P<0.001; odds ratio (OR) 1.158] and anatomic distribution (P=0.027; OR, 1.924) were independent determinants of resectability. ROC analysis revealed that the GTV cut-offs for the determination of the resectability of the upper, middle and lower thoracic portions were 23.57, 22.89 and 22.58 cm3, respectively, with areas under the ROC curves of >0.9. Unweighted Cohen's Kappa tests revealed an excellent performance of the ROC models in the upper, middle and lower thoracic portions with Cohen k-values of 0.913, 0.879 and 0.871, respectively. On the whole, the present study demonstrated that GTV and the anatomic distribution of non-distant metastatic thoracic ESCC may be independent determinants of resectability, and anatomical distribution-based GTV can effectively be used to quantitatively determine resectability.
ABSTRACT
Purpose: To determine whether gross tumor volume (GTV) of adenocarcinoma of esophagogastric junction (AEG) corresponding to cT and cN stages measured on CT could help quantitatively determine resectability. Materials and methods: 343 consecutive patients with AEG, including 279 and 64 randomly enrolled in training cohort (TC) and validation cohort (VC), respectively, underwent preoperative contrast-enhanced CT. Univariate and multivariate analyses for TC were performed to determine factors associated with resectability. Receiver operating characteristic (ROC) analyses were to determine if GTV corresponding to cT and cN stages could help determine resectability. For VC, Cohen's Kappa tests were to assess performances of the ROC models. Results: cT stage, cN stage and GTV were independently associated with resectability of AEG with odds ratios of 4.715, 4.534 and 1.107, respectively. For differentiating resectable and unresectable AEG, ROC analyses showed that cutoff GTV of 32.77 cm3 in stage cT1-4N0-3 with an area under the ROC curve (AUC) of 0.901. Particularly, cutoffs of 27.67 and 32.77 cm3 in stages cT3 and cT4 obtained AUC values of 0.860 and 0.890, respectively; and cutoffs of 27.09, 33.32 and 37.39 cm3 in stages cN1, cN2 and cN3 obtained AUC values of 0.852, 0.821 and 0.902, respectively. In VC, Cohen's Kappa tests verified that the ROC models had good performance in distinguishing between resectable and unresectable AEG (all Cohen's K values > 0.72). Conclusions: GTV, cT and cN stages could be independent determinants of resectability of AEG. And GTV corresponding to cT and cN stages can help quantitatively determine resectability.
ABSTRACT
Purpose: To develop and validate a quantitative model based on gross tumor volume (GTV) of gastric adenocarcinoma (GA) corresponding to N-stage measured at multidetector computed tomography (CT) for preoperative determination of resectability. Materials and methods: 493 consecutive patients with confirmed GA undergoing contrast-enhanced CT two weeks before treatments were randomly enrolled into the training cohort (TC, n = 271), internal validation cohort (IVC, n = 107) and external validation cohort (EVC, n = 115). GTV was measured on CT by multiplying sums of all tumor areas by section thickness. In TC, univariate and multivariate analyses were performed to select factors associated with resectability. Receiver operating characteristic (ROC) analysis was to determine if N-stage based GTV could identify resectability. In IVC and EVC, unweighted Cohen's Kappa tests were to evaluate performances of the ROC models. Results: According to univariate analysis, age, cT stage, cN stage and GTV were related to resectability in TC (all P-values < 0.05), and multivariate analysis suggested that cN stage and GTV were independent risk factors with odds ratios of 1.594 (95% confidence interval [CI]: 1.105-2.301) and 1.055 (95%CI: 1.035-1.076), respectively. ROC analysis in TC revealed the cutoffs of 21.81, 21.70 and 36.93 cm3 to differentiate between resectable and unresectable cancers in stages cN0-3, cN2 and cN3 with areas under the curves of more than 0.8, respectively, which was validated in IVC and EVC with average Cohen k-values of more than 0.72. Conclusions: GTV and cN stage can be independent risk factors of unresectable GA, and N-stage based GTV can help determine resectability.
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OBJECTIVE: To investigate relationship of tumor stage-based gross tumor volume (GTV) of esophageal squamous cell carcinoma (ESCC) measured on computed tomography (CT) with early recurrence (ER) after esophagectomy. MATERIALS AND METHODS: Two hundred and four consecutive patients with resectable ESCC including 159 patients enrolled in the training cohort (TC) and 45 patients in validation cohort (VC) underwent contrast-enhanced CT less than 2 weeks before esophagectomy. GTV was retrospectively measured by multiplying sums of all tumor areas by section thickness. For the TC, univariate and multivariate analyses were performed to determine factors associated with ER. Mann-Whitney U test was conducted to compare GTV in patients with and without ER. Receiver operating characteristic (ROC) analysis was performed to determine if tumor stage-based GTV could predict ER. For the VC, unweighted Cohen's Kappa tests were used to evaluate the performances of the previous ROC predictive models. RESULTS: ER occurred in 63 of 159 patients (39.6%) in the TC. According to the univariate analysis, histologic differentiation, cT stage, cN stage, and GTV were associated with ER after esophagectomy (all P-values < 0.05). Multivariate analysis revealed that cT stage and GTV were independent risk factors with hazard ratios of 3.382 [95% confidence interval (CI): 1.533-7.459] and 1.222 (95% CI: 1.125-1.327), respectively (all P-values < 0.05). Mann-Whitney U tests showed that GTV could help differentiate between ESCC with and without ER in stages cT1-4a, cT2, and cT3 (all P-values < 0.001), and the ROC analysis demonstrated the corresponding cutoffs of 13.31, 17.22, and 17.83 cm3 with areas under the curve of more than 0.8, respectively. In the VC, the Kappa tests validated that the ROC predictive models had good performances for differentiating between ESCC with and without ER in stages cT1-4a, cT2, and cT3 with Cohen k of 0.696 (95% CI, 0.498-0.894), 0.733 (95% CI, 0.386-1.080), and 0.862 (95% CI, 0.603-1.121), respectively. CONCLUSION: GTV and cT stage can be independent risk factors of ER in ESCC after esophagectomy, and tumor stage-based GTV measured on CT can help predict ER.
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UNLABELLED: To study the anti-tumor activity of centipede extract on cervical tumor of mice and its mechanism. METHODS: The tumor-bearing mice were treated with centipede extract from two solvents [ether (CE) and alcohol (CA)] at different comcentration. The mice' life span, tumor inhibition rate and immune function were estimated. RESULTS: No mice died in CE and CA treatment groups and the tumor inhibition rate was 52.85% and 33.65% respectively. Observed the tumor tissue slices with light microscope and found infiltration of tumor cells in striated muscle in the control group but centipede treatment groups had massive necrosis and apoptosis. Karyopyknosis and apoptotic tumor cells were observed in the treatment groups under transmission electron microscopy. Compared with control group, the expression of Bax increased, the expressions of Bcl-2 and Survivin decreased, but the content of VEGF, the indexes of thymus and spleen had no significant change in treatment groups. The number of CD3+ T lymphocytes had no significant change while the ratio of CD4+ and CD8+, the number of CD19+ B lymphocytes decreaed in the CE group. The numbers of CD3+ and CD4+ lymphocytes decreased in the CA group. The pathological examine indicated no obvious change in the tissue slices of mice's liver and kidney, manifested the concentrations of CE and CA between the article's had no visible side effect. CONNCLUSION: The two extracts (CE and CA) can suppress the growth of cervical tumor and its mechanism may be related to Bax and Caspase-3 medicated the mitochondrial signal transit pathway.