Weihua Fu

Clinicopathological and prognostic significance of cancer stem cell markers CD44 and CD133 in patients with gastric cancer: A comprehensive meta-analysis with 4729 patients involved.

Background:In recent years, CD44 and CD133 have been identified as 2 common used cancer stem cell (CSC) markers in gastric cancer. However, the clinicopathological and prognostic value of these markers in gastric cancer remains controversial; moreover, there is lack of comparison of these 2 markers’ roles in clinical applications. A systematic review and meta-analysis was conducted to elucidate these markers’ clinicopathological features and association with prognosis in patients with gastric cancer. Methods:Eligible studies were identified and odds ratios (ORs), hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated. Heterogeneity and sensitivity were analyzed as well. Publication bias was assessed using funnel plots and Egger tests. Results:The meta-analysis included 26 studies involving 4729 patients. High expression of CD44 was associated with Lauren type (intestinal type) (OR, 1.53 [95% CI, 1.02–2.30]; P = 0.038) and lymphatic vessel invasion (OR, 1.36 [95% CI, 1.06–1.76]; P = 0.021). CD133 overexpression was related to high TNM stage (III/IV) (OR, 3.18 [95% CI, 2.48–4.07]; P = 0.000), high depth of invasion (T3/T4) (OR, 2.97 [95% CI, 2.20–4.03]; P = 0.000), lymph node metastasis (OR, 2.82 [95% CI, 2.16–3.69]; P = 0.000), vascular invasion (OR, 6.71 [95% CI, 1.63–27.63]; P = 0.008), and distant metastasis (OR, 2.32 [95% CI, 1.64–3.29]; P = 0.000). In addition, survival analysis demonstrated a significant association between CD44, as well as CD133 and poor 5-year overall survival (HR, 1.87 [95% CI, 1.55–2.26]; P = 0.000; HR, 2.07 [95% CI, 1.76–2.44]; P = 0.000, respectively). Conclusion:These data suggest that upregulated expression of CD44 and CD133 correlates with several clinicopathological features and poor prognosis. Since the related features do not overlap, combined detection of CD44 and CD133 expression can be an especially effective tool for pathological diagnosis and prognostic prediction of gastric cancer patients in clinical applications.

Current status of lymph node micrometastasis in gastric cancer

Lymph node metastasis is one of the most important prognostic factors in patients with gastric cancer. An inadequate number of dissected lymph nodes is an independent risk factor affecting recurrence, even in patients who are node negative. Oddly, certain early-stage patients still experience recurrence or metastasis within a short time, even if they have undergone standard radical mastectomy. Many researchers have attributed these adverse events to lymph node micrometastasis (LNM), which is defined as a microscopic deposit of malignant cells of less than 2 mm in diameter. With the development of diagnostic tools such as immunohistochemistry and reverse transcription-polymerase chain reaction, the rate of detection of LNM has been constantly increasing. Although there is no clear consensus about risk factors for or the definitive clinical significance of LNM, the clinical impact of LNM is remarkable in gastric cancer. For minimally invasive treatment in particular, such as endoscopic submucosal dissection and laparoscopic surgery, accurate diagnosis of LNM is regarded as the potential key to maintaining the balance between curability and safety. This review provides an overview of the definition, detection and significance of LNM in gastric cancer. We also summarize several attention-drawing controversies regarding the treatment of patients who may have LNM.Lymph node metastasis is one of the most important prognostic factors in patients with gastric cancer. An inadequate number of dissected lymph nodes is an independent risk factor affecting recurrence, even in patients who are node negative. Oddly, certain early-stage patients still experience recurrence or metastasis within a short time, even if they have undergone standard radical mastectomy. Many researchers have attributed these adverse events to lymph node micrometastasis (LNM), which is defined as a microscopic deposit of malignant cells of less than 2 mm in diameter. With the development of diagnostic tools such as immunohistochemistry and reverse transcription-polymerase chain reaction, the rate of detection of LNM has been constantly increasing. Although there is no clear consensus about risk factors for or the definitive clinical significance of LNM, the clinical impact of LNM is remarkable in gastric cancer. For minimally invasive treatment in particular, such as endoscopic submucosal dissection and laparoscopic surgery, accurate diagnosis of LNM is regarded as the potential key to maintaining the balance between curability and safety. This review provides an overview of the definition, detection and significance of LNM in gastric cancer. We also summarize several attention-drawing controversies regarding the treatment of patients who may have LNM.

Prognostic and clinicopathological value of Gli-1 expression in gastric cancer: A meta-analysis

Glioma associated oncogene-1 (Gli-1) is considered as a strong positive activator of downstream target genes of hedgehog signal pathway in mammalians. However, its diagnostic and prognostic value in gastric cancer remains unclear and controversial. Therefore, a quantitative meta-analysis was conducted to determine the clinical value of Gli-1 in gastric cancer patients. Twelve eligible articles with 886 gastric cancer patients were included in this meta-analysis. The relationship between Gli-1 expression in gastric cancer patients and clinicopathological features and 5-year overall survival (OS) was evaluated using pooled odds ratios (ORs) and hazard ratio (HR) with 95% confidence intervals (CIs). The meta-analysis showed that the upregulated Gli-1 was associated with sample type (gastric cancer tissues) (OR 10.31, 95%CI 7.14-14.88; P = 0.000), differentiation type (OR 3.76, 95%CI 2.55-5.53; P = 0.000), depth of invasion (OR 8.17, 95%CI 3.60-18.55; P = 0.000), lymph node metastasis (OR 3.97, 95%CI 2.73-5.78; P = 0.000) and high TNM stage (OR 3.65, 95%CI 1.89-7.04; P = 0.000). Three studies including 316 patients were assessed for the correlation between Gli-1 and 5-year OS, which indicated that positive Gli-1 expression was associated with poor prognosis in gastric cancer patients (HR 2.14, 95%CI 1.35-3.40; P = 0.001). Little publication bias was identified by funnel plots and Eggers tests. The sensitivity analysis indicated that no study substantially influenced pooled OR/HR. Taken together, Gli-1 is a credible indicator for highly aggressive tumor with poor prognosis in gastric cancer patients.

CD44v6: A metastasis-associated biomarker in patients with gastric cancer?: A comprehensive meta-analysis with heterogeneity analysis.

Background:The diagnostic and prognostic value of CD44v6 in patients with gastric cancer remains unclear. Therefore, a quantitative meta-analysis was conducted to determine the clinical value of CD44v6 in patients with gastric cancer. Methods:Sixteen studies with 2177 patients were included. Pooled odds ratios (ORs) and hazard ratio (HR) with 95% confidence intervals (CIs) were calculated to estimate the impact of CD44v6 in patients with gastric cancer on clinicopathological features and 5-year overall survival (OS). Sensitivity analysis, subgroup analysis, and regression analysis were introduced to evaluate the heterogeneity across the studies. Publication bias was also explored among the studies. Results:The meta-analysis showed that the upregulated CD44v6 was associated with lymph node metastasis (OR 1.91, 95% CI 1.19–3.08; P = 0.007), distant metastasis (OR 3.41, 95% CI 2.01–5.78; P = 0.000), high TNM stage (OR 2.29, 95% CI 1.10–4.75; P = 0.026), lymphatic vessel invasion (OR 1.59, 95% CI 1.21–2.09; P = 0.001), and vascular invasion (OR 1.57, 95% CI 1.19–2.07; P = 0.001). When excluded 1 study based on sensitivity analysis, pooled HR indicated that CD44v6 positive expression was correlated poor 5-year OS (OR 1.76, 95% CI 1.30–2.39; P = 0.000), meanwhile, heterogeneity was eliminated. The heterogeneity of Lauren type mainly existed in the big sample size subgroup. Different region and publication year might contribute to the heterogeneity of differentiation type. While the heterogeneity of lymph node mainly existed in Asian and big sample size group. Publication bias was observed among 12 studies on lymph node metastasis (Ppublication bias = 0.041), and 5 studies on TNM stage (Ppublication bias = 0.026). Conclusion:Taken together, CD44v6 overexpression might be correlated to the characteristics of tumor metastasis in gastric cancer, consisting with many mechanism studies. Therefore, CD44v6 might present a metastasis-associated biomarker in patients with gastric cancer.

Estimation of physiologic ability and surgical stress (E-PASS) scoring system could provide preoperative advice on whether to undergo laparoscopic surgery for colorectal cancer patients with a high physiological risk.

Abstract Laparoscopic colorectal surgery had been widely used for colorectal cancer patient and showed a favorable outcome on the postoperative morbidity rate. We attempted to evaluate physiological status of patients by mean of Estimation of physiologic ability and surgical stress (E-PASS) system and to analyze the difference variation of postoperative morbidity rate of open and laparoscopic colorectal cancer surgery in patients with different physiological status. In total 550 colorectal cancer patients who underwent surgery treatment were included. E-PASS and some conventional scoring systems were reviewed to examine their mortality prediction ability. The preoperative risk score (PRS) in the E-PASS system was used to evaluate the physiological status of patients. The difference of postoperative morbidity rate between open and laparoscopic colorectal cancer surgeries was analyzed respectively in patients with different physiological status. E-PASS had better prediction ability than other conventional scoring systems in colorectal cancer surgeries. Postoperative morbidities were developed in 143 patients. The parameters in the E-PASS system had positive correlations with postoperative morbidity. The overall postoperative morbidity rate of laparoscopic surgeries was lower than open surgeries (19.61% and 28.46%), but the postoperative morbidity rate of laparoscopic surgeries increased more significantly than in open surgery as PRS increased. When PRS was more than 0.7, the postoperative morbidity rate of laparoscopic surgeries would exceed the postoperative morbidity rate of open surgeries. The E-PASS system was capable to evaluate the physiological and surgical risk of colorectal cancer surgery. PRS could assist preoperative decision-making on the surgical method. Colorectal cancer patients who were assessed with a low physiological risk by PRS would be safe to undergo laparoscopic surgery. On the contrary, surgeons should make decisions prudently on the operation method for patient with a high physiological risk.