Laparoscopy is non-inferior to open surgery for rectal cancer: A systematic review and meta-analysis.

BACKGROUND: Laparoscopic surgery has been endorsed by clinical guidelines for colon cancer, but not for rectal cancer on account of unapproved oncologic equivalence with open surgery. AIMS: We started this largest-to-date meta-analysis to comprehensively evaluate the safety and efficacy of laparoscopy in the treatment of rectal cancer compared with open surgery. MATERIALS & METHODS: Both randomized and nonrandomized controlled trials comparing laparoscopic proctectomy and open surgery between January 1990 and March 2020 were searched in PubMed, Cochrane Library and Embase Databases (PROSPERO registration number CRD42020211718). The data of intraoperative, pathological, postoperative and survival outcomes were compared between two groups. RESULTS: Twenty RCTs and 93 NRCTs including 216,615 patients fulfilled the inclusion criteria, with 48,888 patients received laparoscopic surgery and 167,727 patients underwent open surgery. Compared with open surgery, laparoscopic surgery group showed faster recovery, less complications and decreased mortality within 30 days. The positive rate of circumferential margin (RR = 0.79, 95% CI: 0.72 to 0.85, p < 0.0001) and distal margin (RR = 0.75, 95% CI: 0.66 to 0.85 p < 0.0001) was significantly reduced in the laparoscopic surgery group, but the completeness of total mesorectal excision showed no significant difference. The 3-year and 5-year local recurrence, disease-free survival and overall survival were all improved in the laparoscopic surgery group, while the distal recurrence did not differ significantly between the two approaches. CONCLUSION: Laparoscopy is non-inferior to open surgery for rectal cancer with respect to oncological outcomes and long-term survival. Moreover, laparoscopic surgery provides short-term advantages, including faster recovery and less complications.

Prognostic value of YKL-40 in colorectal carcinoma patients: A meta-analysis.

BACKGROUND: In recent years, the predictive role of YKL-40 for long-term survival in colorectal cancer patients has been gradually investigated. However, whether it is a reliable and valuable prognostic indicator for patients with colorectal carcinoma has not been verified. AIM: To identify the prognostic value of serum/plasma concentration of YKL-40 or expression status of YKL-40 in tumor cells in colorectal carcinoma patients. METHODS: Several electronic databases including the PubMed, EMBASE, Web of Science, CNKI, VIP and WanFang were searched for relevant studies. The hazard ratios (HR) and 95% confidence intervals (CI) were combined and the primary and secondary outcomes were overall survival (OS) and progression-free survival (PFS), respectively. All statistical analysis were conducted by STATA 15.0 software. RESULTS: A total of nine studies involving 2545 patients were included. The pooled results indicated that YKL-40 was significantly associated with poor OS (HR = 1.80, 95%CI: 1.32-2.45, P < 0.001) and PFS (HR = 1.62, 95%CI: 1.22-2.16, P = 0.001). Subgroup analysis stratified by the treatment, tumor type and source of YKL-40 showed similar results. CONCLUSION: Elevated serum/plasma concentration of YKL-40 or positive expression in tumor cells was related with worse prognosis of colorectal carcinoma patients. YKL-40 might serve as a novel and reliable indicator for the evaluation of prognosis in colorectal cancer.

Intrathecally administered pizotifen alleviates neuropathic and inflammatory pain in mice by enhancing GABAergic inhibition.

Chronic pain, such as chronic neuropathic pain and chronic inflammatory pain, is often difficult to manage and bring great trouble to patients. 5-HT plays a key role in the process of pain transmission both in centrally and peripherally. Tricyclic antidepressants (TCA) such as amitriptyline are classical 5-HT reuptake inhibitors, are recommended as the first-line treatment for chronic pain. Pizotifen, a 5-HT2 receptor antagonist, is currently used in the prevention of vascular headaches. However, the antinociceptive effect of pizotifen on non-headache pain especially chronic pain in the spinal level is still unknown. Here we find that intrathecal pizotifen attenuates neuropathic and inflammatory pain mainly due to elevated GABAergic synaptic inhibition. Neuropathic pain is induced by segmental spinal nerve ligation (SNL), and inflammatory pain is induced by intraplantar injection of complete Freund's adjuvant (CFA). Both in SNL and CFA mice, spinally administered pizotifen reduced mechanical and thermal hyperalgesia dose-dependently. Since the levels of GAD65/67 were increased, and the frequency of mIPSCs in the spinal dorsal horn was increased, together with the antinociceptive effect being reversed by both GABAAR and GAD blockade, this antinociceptive effect might be generated from strengthened GABAergic inhibition. Furthermore, high dose of pizotifen (5 µg) weakly affected motor performance and did not influence the locomotor activity in normal animals. In summary, our findings suggest that pizotifen strengthens the inhibitory synaptic transmission and exerts antinociceptive effect on both neuropathic pain and inflammatory pain in the spinal cord, and may serve as a promising remedy for chronic pain.

Effects of CYP2C19 Genetic Polymorphisms on the Pharmacokinetic and Pharmacodynamic Properties of Clopidogrel and Its Active Metabolite in Healthy Chinese Subjects.

PURPOSE: Some studies in the white population have shown that carriers of at least 1 loss-of-function allele in the gene that encodes the cytochrome P-450 2C19 isozyme (CYP2C19) have lower levels of the clopidogrel active metabolite (CAM) and a reduced antiplatelet effect of clopidogrel. However, data are limited regarding the association between CYP2C19 genetic variants and exposure to CAM and on the pharmacodynamic properties of CAM in the Chinese population. Data from the white population cannot be extrapolated to the Chinese population because of the marked interethnic differences in CYP2C19 variants. This study was aimed to investigate the influence of CYP2C19 genetic polymorphisms on the pharmacokinetic properties of CAM and the antiplatelet effect of clopidogrel in healthy Chinese volunteers, and to provide evidence for the role of a CYP2C19 genotyping test in predicting the antiplatelet effect of clopidogrel in the Chinese population. METHODS: Twenty healthy subjects received a single 300-mg dose of clopidogrel and were assigned to 1 of 3 groups according to CYP2C19 genotype: CYP2C19 *1/*1 (normal metabolizers [NM]; n = 8), CYP2C19 *1/*2 or *3 (intermediate metabolizers [IM]; n = 10) and CYP2C19 *2/*2 or *3 and *3/*3 (poor metabolizers [PM]; n = 2). Blood samples were collected at baseline and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours after administration. The plasma concentrations of clopidogrel and CAM were analyzed by LC-MS/MS, and adenosine diphosphate-induced platelet aggregation was measured by light-transmittance aggregometry. FINDINGS: There were no significant differences in Cmax and AUC0-t of clopidogrel prodrug in the NM group compared with the IM and PM groups. The mean CAM Cmax value was significantly higher in the NM group than in IM and PM groups (45.39 [12.57] vs 29.15 [7.92] ng/mL [P = 0.003] and 19.55 [2.19] ng/mL [P = 0.004], respectively). The mean CAM AUC0-t value was significantly higher in the NM group than in the IM and PM groups (61.05 [21.63] vs 37.67 [11.01] ng · h/mL [P = 0.007] and 27.08 [2.72] ng · h/mL [P = 0.016]). The NM group exhibited a significantly higher percentage of inhibition of platelet aggregation than did the IM or PM group (P = 0.001). The correlations between the pharmacokinetic properties (Cmax, AUC0-t) of CAM and the pharmacodynamic data (maximal and inhibition of platelet aggregation) were significant (both, Pearson r > 0.5 and P < 0.01). IMPLICATION: In these healthy Chinese subjects, carriers of CYP2C19 loss-of-function allele(s) had significantly reduced exposure of CAM and decreased levels of inhibition of platelet aggregation with clopidogrel; these genotypes therefore might be a determinant for the formation of CAM and its antiplatelet effects. Study identifier: ChiCTR-OCH-14004382.

New views and possibilities of antidiabetic drugs in treating and/or preventing mild cognitive impairment and Alzheimer's Disease.

Mounting evidence suggests that diabetes mellitus (DM) is associated with mild cognitive impairment (MCI), vascular dementia and Alzheimer's disease (AD). Biological, clinical and epidemiological data support a close link between DM and AD. Increasingly, studies have found that several antidiabetic agents can promote neurogenesis, and clinically ameliorate cognitive and memory impairments in different clinical settings. Data has shown that these antidiabetic drugs positively affect mitochondrial and synaptic function, neuroinflammation, and brain metabolism. Evidence to date strongly suggests that these antidiabetic drugs could be developed as disease-modifying therapies for MCI and AD in patients with and without diabetes.

Antifreeze and cryoprotective activities of ice-binding collagen peptides from pig skin.

A novel "hyperactive" ice-binding peptide from porcine collagen was prepared by alkaline protease hydrolysis and a series of column chromatography separations, and then its antifreeze and cryoprotective properties were reported. Using differential scanning calorimetry (DSC), the thermal hysteresis (TH) of ice-binding collagen peptides was closely related to their concentration and crystal fraction. Collagen hydrolysates with maximal TH were obtained by hydrolysis at pH 8.0, DH 15.0%, and 5% alkaline protease at 55°C. After purification by column chromatography, the AP-3 ice-binding collagen peptide (GLLGPLGPRGLL) with 1162.8Da molecular weights exhibited the highest TH (5.28°C), which can be classified as "hyperactive". Recrystallisation and melt-resistance of ice cream were improved by AP-3 ice-binding collagen peptide at 0.2% (w/v) in a similar manner to natural antifreeze proteins. Moreover, the addition of AP-3 collagen peptides in ice cream greatly elevated the glass transition temperature (Tg) to -17.64°C.

[Expression of CCAAT/enhancer binding protein beta in human gastric carcinoma and its clinical significance].

OBJECTIVE: To explore the expression of CCAAT/enhancer binding protein beta (CEBPB) in gastric carcinoma tissues and its association with clinicopathological features and prognosis. METHODS: CEBPB protein expression level was detected by immunohistochemistry method in resected gastric carcinomas and adjacent gastric mucosa tissues (n=81), and its association with clinicopathological features and prognosis was analyzed. RESULTS: The immunohistochemical staining of CEBPB was predominantly in the nucleus with some cytoplasmic staining. As a result, 16% (13/81) of the gastric carcinomas were stained positively, whereas there was hardly positive expression in adjacent gastric mucosa tissues. There was a significant association between the expression of CEBPB and distant metastasis on univariate analysis (P<0.05). The median survival time in patients with positive CEBPB expression was significantly lower than those with negative CEBPB expression (19.4 months vs. 45.2 months, P=0.024). Multivariable analysis showed that CEBPB was independently associated with prognosis (HR=2.544, 95%CI:1.154-5.610, P=0.021). CONCLUSION: Up-regulation of CEBPB suggests poor prognosis in patients with gastric cancer.

PTK7 as a novel marker for favorable gastric cancer patient survival.

BACKGROUND AND OBJECTIVES: Protein tyrosine kinase 7 (PTK7) plays important functions in several cancer types but its expression in gastric cancer remains unknown. This study was designed to investigate PTK7 expression in gastric cancer. METHODS: PTK7 expression was assessed by immunohistochemistry in 201 gastric cancer patients. The relationship between PTK7 expression and clinicopathological features and patients prognosis were statistically analyzed. RESULTS: PTK7 expression was detected in 56.72% (114 of 201) of gastric cancer patients. The immunostaining was predominantly localized in the cytoplasm. The statistical analyses showed that PTK7 expression was more frequently detected in patients with well-differentiated tumors (P = 0.001). Furthermore, PTK7 expression was significantly related to the favorable overall survival (OS; P = 0.012) and disease-free survival (DFS; P = 0.009). Multivariate Cox regression analyses revealed that PTK7 expression was an independent prognostic factor for both favorable OS (P = 0.028) and DFS (P = 0.012). CONCLUSION: Our findings demonstrate that PTK7 can serve as a novel prognostic biomarker for gastric cancer patients.

[Clinical value of serum CEA, CA19-9, CA72-4 and CA242 in the diagnosis and prognosis of gastric cancer].

OBJECTIVE: To investigate the clinical value of tumor markers CEA, CA19-9, CA72-4 and CA242 in the diagnosis and prognosis of patients with gastric cancer. METHODS: One hundred and sixty gastric cancer patients who had received treatment from 2002 to 2007 at the Beijing Cancer Hospital were retrospectively analyzed. Blood samples were taken from patients upon admission to the hospital, and CEA, CA19-9, CA72-4, CA242 levels were detected. Statistical analysis was performed to identify the clinical value of these tumor markers in diagnosis and prognosis. RESULTS: On initial diagnosis, the positive rates of CEA, CA19-9, CA72-4 and CA242 were 37.7%, 26.7%, 37.6% and 21.3%, respectively, and the positive rate of combined detection was 62.9%. CEA was more frequently positive in patients with lymph node metastasis (P=0.029); CA72-4 was more frequently positive in patients with vascular involvement and advanced stage (P=0.039, P=0.011). Multivaraite analysis showed that CA72-4 was an independent prognostic factor (P=0.012). Patients with positive CA72-4 carried a 2.147-fold increased risk of death than those with negative CA72-4. Kaplan-Meier analysis showed that patients with positive CA19-9 or positive CA72-4 had worse survival than those with negative CA19-9 or CA72-4 (P=0.006, P=0.002). CONCLUSIONS: Tumor markers including CEA, CA19-9, CA72-4 and CA242 have clinical significance and prognostic value in patients with gastric cancer. Combined detection of four tumor markers can increase the positive rate. CA72-4 is an independent prognostic factor. CA19-9 and CA72-4 are associated with the prognosis of patients with gastric cancer.

Over-expression of Metastasis-associated in Colon Cancer-1 (MACC1) Associates with Better Prognosis of Gastric Cancer Patients.

OBJECTIVE: The aim of this study was to detect metastasis-associated in colon cancer-1 (MACC1) expression in Chinese gastric cancer and analyze the relationship between MACC1 expression and postoperative survival. METHODS: The expression of MACC1 and c-MET protein in a sample of 128 gastric cancer tissues was detected by immunohistochemistry. A retrospective cohort study on the prognosis was carried out and data were collected from medical records. RESULTS: The positive rate of MACC1 protein expression in gastric cancer was 47.66%, higher than that in adjacent noncancerous mucosa (P<0.001). MACC1 protein expression was not related to the clinicopathological variables involved. Kaplan-Meier analysis revealed that the survival of MACC1 positive group tended to be better than that of MACC1 negative group, particularly in patients with stage III carcinoma (P=0.032). Cox regression analysis revealed that MACC1 protein over-expression in gastric cancer tended to be a protective factor with hazard ratio of 0.621 (P=0.057). Immunohistochemical analysis showed that the positive rate of c-MET protein expression was much higher in cases with positive MACC1 expression in gastric cancer (P=0.002), but P53 expression was not associated with MACC1 expression. CONCLUSION: MACC1 over-expression implies better survival and may be an independent prognostic factor for gastric cancer in Chinese patients.

S100A6 overexpression is associated with poor prognosis and is epigenetically up-regulated in gastric cancer.

S100A6 has been implicated in a variety of biological functions as well as tumorigenesis. In this study, we investigated the expression status of S100A6 in relation to the clinicopathological features and prognosis of patients with gastric cancer and further explored a possible association of its expression with epigenetic regulation. S100A6 expression was remarkably increased in 67.5% of gastric cancer tissues as compared with matched noncancerous tissues. Statistical analysis demonstrated a clear correlation between high S100A6 expression and various clinicopathological features, such as depth of wall invasion, positive lymph node involvement, liver metastasis, vascular invasion, and tumor-node metastasis stage (P < 0.05 in all cases), as well as revealed that S100A6 is an independent prognostic predictor (P = 0.026) significantly related to poor prognosis (P = 0.0004). Further exploration found an inverse relationship between S100A6 expression and the methylation status of the seventh and eighth CpG sites in the promoter/first exon and the second to fifth sites in the second exon/second intron. In addition, the level of histone H3 acetylation was found to be significantly higher in S100A6-expressing cancer cells. After 5-azacytidine or trichostatin A treatment, S100A6 expression was clearly increased in S100A6 low-expressing cells. In conclusion, our results suggested that S100A6 plays an important role in the progression of gastric cancer, affecting patient prognosis, and is up-regulated by epigenetic regulation.

A simple and sensitive HPLC-ESI-MS/MS method for the determination of andrographolide in human plasma.

A liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) method for the determination of andrographolide in human plasma was established. Dehydroandrographolide was used as the internal standard (I.S.). The plasma samples were deproteinized with methanol and separated on a Hanbon C(18) column with a mobile phase of methanol-water (70:30, v/v). HPLC-ESI-MS/MS was performed in the selected ion monitoring (SIM) mode using target ions at [M-H(2)O-H](-), m/z 331.1 for andrographolide and [M-H](-), m/z 331.1 for the I.S. Calibration curve was linear over the range of 1.0-150.0ng/mL. The chromatographic separation was achieved in less than 6.5min. The lower limits of quantification (LLOQ) was 1.0ng/mL. The intra and inter-run precisions were less than 6.95 and 7.22%, respectively. The method was successfully applied to determine the plasma concentrations of andrographolide in Chinese volunteers.

Optimizing high-performance liquid chromatography method with fluorescence detection for quantification of tamoxifen and two metabolites in human plasma: application to a clinical study.

We set an improved high-performance liquid chromatography method with fluorescence detection HPLC-FLU assay with more sensitivity and precision for the quantification of tamoxifen and two metabolites: 4-hydroxytamoxifen and N-desmethyltamoxifen. The compounds and internal standard, mexiletine, were separated with an Agilent Extend C18 column set at 65 degrees C and a mobile phase of methanol-1% triethylamine aqueous solution (pH 11; 82:18, v/v). The detection system utilized offline ultraviolet irradiation to convert the analytes to their respective photocyclisation products, followed by fluorescence detection (lambda ex=260 nm and lambda em=375 nm). The limits of quantification for tamoxifen, N-desmethyltamoxifen and 4-hydroxytamoxifen in plasma were improved to 0.5, 0.5 and 0.1 ng/ml, respectively. And the retention times for tamoxifen, N-desmethyltamoxifen and 4-hydroxytamoxifen were minimized to 11, 10 and 3.9 min, respectively. A single stage liquid-liquid extraction method for determination of these triphenylethylene drugs in plasma was developed, with high extraction efficiency and rapid sample treatment for target compounds. The method has been validated for use in a clinical bioavailability research of tamoxifen.