Survival landscape of different tumor regression grades and pathologic complete response in rectal cancer after neoadjuvant therapy based on reconstructed individual patient data.

BACKGROUND: Neoadjuvant therapy can lead to different tumor regression grades (TRG) in rectal cancer after neoadjuvant therapy. The purposes of this study are to investigate the relationships among TRG, pathologic complete response (pCR) and long-term survival, on the basis of reconstructed individual patient data (IPD). METHODS: The PubMed, Embase, Ovid and Cochrane CENTRAL databases were searched. The primary endpoint was to evaluate the survival landscape of different TRGs after neoadjuvant therapy and the secondary endpoint was to evaluate the associations between pCR and survival. IPD were reconstructed with Kaplan-Meier curves. RESULTS: The 10-year overall survival (OS) and 5-year disease-free survival (DFS) were clearly higher in the pCR group than in the non-pCR (npCR) group (80.5% vs. 48.3, 90.1% vs. 69.8%). Furthermore, the OS and DFS increased with improvement in tumor regression after neoadjuvant therapy. According to the IPD, the pCR group had longer OS (HR = 0.240, 95% CI = 0.177-0.325, p < 0.001) and DFS (HR = 0.274, 95% CI = 0.205-0.367, p < 0.001) than the npCR group. Better tumor regression was associated with better survival outcomes (p < 0.005). Direct calculation of published HR values yielded similar results. CONCLUSIONS: Our results indicate a positive relationship between better tumor regressions and improved survival benefits among the npCR group and patients with rectal cancer achieving pCR had much longer OS and DFS than patients achieving npCR, presenting a survival landscape of different TRGs and pCR in rectal cancer after neoadjuvant therapy.

Impact of timing of adjuvant chemotherapy on survival in stage III colon cancer: a population-based study.

BACKGROUND: There is no consensus regarding the optimal time to initiate adjuvant chemotherapy after surgery for stage III colon cancer, and the relevant postoperative complications that cause delays in adjuvant chemotherapy are unknown. METHODS: Eligible patients aged ≥66 years who were diagnosed with stage III colon cancer from 1992 to 2008 were identified using the linked Surveillance, Epidemiology, and End Results-Medicare database. Kaplan-Meier analysis and a Cox proportional hazards model were utilized to evaluate the impact of the timing of adjuvant chemotherapy on overall survival (OS). RESULTS: A total of 18,491 patients were included. Delayed adjuvant chemotherapy was associated with worse OS (9-12 weeks: hazard ratio [HR] = 1.222, 95% confidence interval [CI] = 1.063-1.405; 13-16 weeks: HR = 1.252, 95% CI = 1.041-1.505; ≥ 17 weeks: HR = 1.969, 95% CI = 1.663-2.331). The efficacies of adjuvant chemotherapy within 5-8 weeks and ≤4 weeks were similar (HR = 1.045, 95% CI = 0.921-1.185). Compared with the non-chemotherapy group, chemotherapy initiated at ≥21 weeks did not significantly improve OS (HR = 0.882, 95% CI = 0.763-1.018). Patients with postoperative complications, particularly cardiac arrest, ostomy infection, shock, and septicemia, had a significantly higher risk of a 4- to 11-week delay in adjuvant chemotherapy (p < 0.05). CONCLUSIONS: Adjuvant chemotherapy initiated within 8 weeks was acceptable for patients with stage III colon cancer. Delayed adjuvant chemotherapy after 8 weeks was significantly associated with worse OS. However, adjuvant chemotherapy might still be useful even with a delay of approximately 5 months. Moreover, postoperative complications were significantly associated with delayed adjuvant chemotherapy.

Which is better for gastric cancer patients, perioperative or adjuvant chemotherapy: a meta-analysis.

BACKGROUND: The preferred chemotherapy method for gastric cancer continues to be matter of debate. We performed a meta-analysis to comparing prognosis and safety between perioperative chemotherapy and adjuvant chemotherapy to identify the better chemotherapy option for gastric cancer. METHODS: We searched the PubMed, EMBASE, Cochrane Library, and Ovid databases for eligible studies until February 2016. The main endpoints were prognostic value (hazard ratio [HR] for overall survival [OS] and 1-, 2-, 3-, and 5-year survival rate), response rate of chemotherapy, radical resection rate, post-operative complication rate, and adverse effects of chemotherapy. RESULTS: Five randomized controlled trials and six clinical controlled trials involving 1,240 patients were eligible for analysis. Compared with the adjuvant chemotherapy group, the perioperative chemotherapy group had significantly better prognosis (HR, 0.74; 95 % CI, 0.61 to 0.89; P < 0.01). The difference between the two groups remained significant in the studies that used combination chemotherapy as the neoadjuvant chemotherapy regimen (HR, 0.59; 95 % CI, 0.46 to 0.76; P < 0.01) but were not significant in the studies that used fluoropyrimidine monotherapy (HR, 0.93; 95 % CI, 0.56 to 1.55; P = 0.84). Furthermore, the two groups showed no significant differences in the post-operative complication rates (relative risk, 0.98; 95 % CI, 0.63 to 1.51; P = 0.91) or adverse effects of chemotherapy (P > 0.05 for all adverse effects). CONCLUSION: Perioperative chemotherapy showed improved survival compared to adjuvant chemotherapy for gastric cancer. In addition, combination chemotherapy resulted in better survival compared to monotherapy in the neoadjuvant chemotherapy regimens.

Meta-analysis of the laparoscopic versus open colorectal surgery within fast track surgery.

BACKGROUND: Laparoscopic methods and fast-track surgery (FTS) can enhance recovery and reduce postoperative hospital stay. However, whether laparoscopic surgery can provide short-term benefits within FTS is controversial. Thus, we conducted a meta-analysis of published studies to evaluate the effect of laparoscopic colorectal surgery within FTS. METHODS: We searched PubMed, EMBASE, Cochrane Library, and Ovid databases for eligible studies. Endpoints were duration of postoperative hospital stay, time to first bowel movement, total postoperative complication rate, readmission rate, mortality within 30 days after surgery, and conversation rate of laparoscopic surgery. RESULTS: Four randomized controlled trials and six clinical controlled trials (1510 patients) were eligible for analyses. Duration of postoperative hospital stay (weighted mean difference, -1.65 days; p < 0.001), time to first bowel movement (-1.13 days; p < 0.001), total postoperative complication rate (risk ratio [RR], 0.65; p < 0.001), readmission rate (0.46; p < 0.001), and mortality (0.45; p < 0.001) were significantly reduced in the laparoscopic surgery group. Overall conversion rate of laparoscopic surgery was 11.1%. Subgroup analyses based on each FT element demonstrated that studies without the element "prevention of hypothermia," "no bowel preparation," or "no routine use of drains" did not show significant differences between two groups with regard to duration of postoperative hospital stay or total prevalence of postoperative complications. CONCLUSION: Within FTS, laparoscopic methods can significantly shorten postoperative hospital stay, accelerate postoperative recovery, and enhance safety in colorectal surgery. The FT elements "prevention of hypothermia," "no bowel preparation," and "no routine use of drains" may play important parts in the combined effect of these two methods.

Aspirin and nonsteroidal anti-inflammatory drugs after but not before diagnosis are associated with improved breast cancer survival: a meta-analysis.

PURPOSE: The association between nonsteroidal anti-inflammatory drugs (NSAIDs) and breast cancer survival is still controversial. The aim of our meta-analysis was to assess the survival benefit of NSAIDs. METHODS: A literature search was conducted in PubMed and EMBASE (to September 2014). A meta-analysis was performed with hazard ratios (HRs) and 95% confidence intervals (CIs) as the effect measures. Subgroup analyses were based on time of NSAID use (before and after diagnosis), medication type (aspirin and other nonaspirin NSAIDs), and study design (cohort and case-control studies). RESULTS: There were 16 eligible studies. Use of NSAIDs after diagnosis was significantly inversely associated with relapse/metastasis (HR 0.69, 95% CI 0.59-0.80) and tended toward potentially protective effects on all-cause mortality, although significance was not reached (HR 0.79, 95% CI 0.61-1.02). In cohort studies, the association between post-diagnostic use of NSAIDs and breast cancer survival was stronger with reduced heterogeneity (breast-cancer-specific mortality: HR 0.65, 95% CI 0.48-0.89, I(2) = 65.3%; all-cause mortality: HR 0.73, 95% CI 0.57-0.92, I(2) = 83.2%; relapse/metastasis: HR 0.73, 95% CI 0.61-0.86, I(2) = 48.3%). Aspirin use after diagnosis was significantly associated with breast-cancer-specific mortality (HR 0.69, 95% CI 0.50-0.96) and relapse/metastasis (HR 0.75, 95% CI 0.56-1.00), and tended toward a protective effect on all-cause mortality, although significance was not reached (HR 0.79, 95% CI 0.60-1.03). Including cohort studies only, we obtained similar results and post-diagnostic use of aspirin was significantly associated with all-cause mortality (HR 0.72, 95% CI 0.56-0.93). CONCLUSIONS: NSAIDs and aspirin after but not before diagnosis were associated with improved breast cancer survival, including breast-cancer-specific mortality, all-cause mortality, and relapse/metastasis.

Laparoscopic resection with natural orifice specimen extraction versus conventional laparoscopy for colorectal disease: a meta-analysis.

PURPOSE: We wished to determine the effects of laparoscopic resection using natural orifice specimen extraction (NOSE) for patients with colorectal disease through a meta-analysis. METHODS: A study search was undertaken in PubMed, EMBASE, and Cochrane databases for eligible studies until December 2014. Duration of hospital stay, operation time, time to first flatus, pain score, cosmetic result, postoperative complications, and disease-free survival (DFS) were the main endpoints. The results were analyzed using RevMan v5.3. RESULTS: Nine clinical studies involving 837 patients were included for final analyses. Laparoscopic resection with NOSE had a shorter duration of hospital stay (weighted mean difference (WMD) = -0.62 days, 95 % confidence interval (CI) [-0.95, -0.28], p < 0.01) and time to first flatus (WMD = -0.59 days, 95 % CI [-0.78, -0.41], p < 0.01), less postoperative pain (WMD = -1.43, 95 % CI [-1.95, -0.90], p < 0.01), and postoperative complications (odds ratio (OR) = 0.51, 95 % CI [0.36, 0.74], p < 0.01) with better cosmetic result (WMD = 1.37, 95 % CI [0.59, 2.14], p < 0.01). However, the operation time was significantly longer in the NOSE group (WMD = 20.97 min, 95 % CI [4.33, 37.62], p = 0.01). No significant difference was observed in DFS (hazard ratio (HR) = 0.88, 95 % CI [0.49, 1.57], p = 0.67). CONCLUSION: Our meta-analysis supported the notion that laparoscopic resection with NOSE for colorectal disease can significantly reduce the duration of hospital stay, accelerate postoperative recovery with better cosmetic results, and in particular, result in less postoperative pain and fewer complications.

Regulatory Roles of Non-Coding RNAs in Colorectal Cancer.

Non-coding RNAs (ncRNAs) have recently gained attention because of their involvement in different biological processes. An increasing number of studies have demonstrated that mutations or abnormal expression of ncRNAs are closely associated with various diseases including cancer. The present review is a comprehensive examination of the aberrant regulation of ncRNAs in colorectal cancer (CRC) and a summary of the current findings on ncRNAs, including long ncRNAs, microRNAs, small interfering RNAs, small nucleolar RNAs, small nuclear RNAs, Piwi-interacting RNAs, and circular RNAs. These ncRNAs might become novel biomarkers and targets as well as potential therapeutic tools for the treatment of CRC in the near future and this review may provide important clues for further research on CRC and for the selection of effective therapeutic targets.

[Effect of 18-ß Glycyrrhetinic Acid on the Endoplasmic Reticulum of Nasal Epithelial Cells in Allergic Rhinitis Model Rats].

OBJECTIVE: To explore the effect of 18-ß glycyrrhetinic acid (GA) on the endoplasmic reticulum of nasal epithelial cells in allergic rhinitis (AR) model rats. METHODS: Totally 96 Wistar rats were randomly divided into the blank group, the AR model group, the loratadine group, the GA group, 24 in each group. AR models were established by peritoneally injecting ovalbumin (OVA). Morphological scoring was performed. GA at 21. 6 mg/kg was intragastrically administered to rats in the GA group. Nasal mucosal tissues were taken for electron microscopic examinations at the second, fourth, sixth, and tenth week after drug intervention. RESULTS: The overlapping score was 2.10 ± 0.45 in the blank group, 5.10 ± 0.56 in the loratadine group, 5.10 ± 0.56 in the AR model group, 5.20 ± 0.78 in the GA group, showing statistical difference when compared with the blank group (P < 0.01). Results under transmission electron microscope showed that the number of the endoplasmic reticulum increased in the AR model group, with obvious cystic dilatation, a lot of vacuole formation, and degranulation. A large number of free ribosomes could be seen in cytoplasm. With persistent allergen exposure, changes mentioned above was progressively aggravated in the endoplasmic reticulum of nasal mucosal epithelium in the AR model group. But the dilation of endoplasmic reticulum, vacuole formation, and degranulation were relieved in the GA group, and got close to those of the blank group. CONCLUSION: 18-ß GA could improve the expansion, vacuolization, and degranulation of the endoplasmic reticulum of nasal epithelial cells in AR model rats.

ILEI: a novel marker for epithelial-mesenchymal transition and poor prognosis in colorectal cancer.

AIMS: Accumulating evidence over the past decade has shown that abnormal activation of epithelial to mesenchymal transition (EMT) contributes to tumour progression and metastasis in colorectal cancer (CRC). In this study, we investigated the expression of interleukin-like EMT inducer (ILEI) and EMT-associated markers (E-cadherin, vimentin) in CRC tissues and determined the correlations between ILEI expression and clinicopathological characteristics, prognosis and EMT in CRC. METHODS AND RESULTS: In total, 194 patients diagnosed with CRC based on histopathological evaluation and those subjected to surgical resection at the First Hospital of China Medical University between 2003 and 2005 were examined. Immunohistochemical staining for ILEI, vimentin and E-cadherin was performed for each specimen. Cytoplasmic overexpression of ILEI usually accompanied down-regulation of E-cadherin and positive expression of vimentin. Conversely, ILEI was simultaneously down-regulated with overexpression of E-cadherin and negative expression of vimentin. ILEI overexpression was associated significantly with T-stage, N-stage, TNM stage and EMT phenotype (P = 0.024, <0.001, <0.001 and <0.001, respectively). Multivariate analysis revealed that ILEI expression was an independent prognostic factor for patient survival. CONCLUSIONS: Our findings indicate that cytoplasmic ILEI expression is a potential marker of EMT and tumour progression in CRC. ILEI is an independent predictive factor associated with poor prognosis in CRC.

Fast-track surgery versus traditional perioperative care in laparoscopic colorectal cancer surgery: a meta-analysis.

BACKGROUND: Both laparoscopic and fast-track surgery (FTS) have shown some advantages in colorectal surgery. However, the effectiveness of using both methods together is unclear. We performed this meta-analysis to compare the effects of FTS with those of traditional perioperative care in laparoscopic colorectal cancer surgery. METHODS: We searched the PubMed, EMBASE, Cochrane Library, and Ovid databases for eligible studies until April 2014. The main end points were the duration of the postoperative hospital stay, time to first flatus after surgery, time of first bowel movement, total postoperative complication rate, readmission rate, and mortality. RESULTS: Five randomized controlled trials and 5 clinical controlled trials with 1,317 patients were eligible for analysis. The duration of the postoperative hospital stay (weighted mean difference [WMD], -1.64 days; 95% confidence interval [CI], -2.25 to -1.03; p < 0.001), time to first flatus (WMD, -0.40 day; 95% CI, -0.77 to -0.04; p = 0.03), time of first bowel movement (WMD, -0.98 day; 95% CI, -1.45 to -0.52; p < 0.001), and total postoperative complication rate (risk ratio [RR], 0.67; 95% CI, 0.56-0.80; p < 0.001) were significantly reduced in the FTS group. No significant differences were noted in the readmission rate (RR, 0.64; 95% CI, 0.41-1.01; p = 0.06) or mortality (RR, 1.55; 95% CI, 0.42-5.71; p = 0.51). CONCLUSION: Among patients undergoing laparoscopic colorectal cancer surgery, FTS is associated with a significantly shorter postoperative hospital stay, more rapid postoperative recovery, and, notably, greater safety than is expected from traditional care.

Which is the best postoperative chemotherapy regimen in patients with rectal cancer after neoadjuvant therapy?

BACKGROUND: There is no general agreement about whether patients who have already received neoadjuvant chemoradiotherapy need further postoperative chemotherapy based on 5-fluorouracil(5-FU) or 5-FU plus oxaliplatin. METHODS: Medicare beneficiaries from 1992 to 2008 with Union for International Cancer Control ypStages I to III primary carcinoma of the rectum who underwent 5-FU-based neoadjuvant chemoradiotherapy and surgery for curative intent were identified through the Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked database. A Cox proportional hazards model and propensity score-matched techniques were used to evaluate the effect of treatment on survival. RESULTS: For patients with resected rectal cancer who have already received 5-FU-based neoadjuvant chemoradiotherapy, postoperative 5-FU-based chemotherapy did not prolong cancer-specific survival (CSS) in ypStage I (P = 0.960) and ypStage II (P = 0.134); however, it significantly improved the CSS in ypStage III (hazard ratio = 1.547, 95% CI = 1.101-2.173, P = 0.012). No significant differences in survival between the 5-FU group and oxaliplatin group were observed. CONCLUSIONS: For patients with resected rectal cancer who have already received 5-FU-based neoadjuvant chemoradiotherapy, postoperative 5-FU-based chemotherapy prolongs the CSS of groups in ypStage III. Adding oxaliplatin to fluoropyrimidines in the postoperative chemotherapy did not improve the CSS for patients who received neoadjuvant chemoradiotherapy.

The Efficacy and Safety of Celecoxib in Addition to Standard Cancer Therapy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

The purpose of this meta-analysis was to evaluate the efficacy and safety of celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, in addition to standard anticancer therapy. Randomized controlled trials (RCTs) that evaluated the efficacy and safety of celecoxib-combined cancer therapy were systematically searched in PubMed and Embase databases. The endpoints were overall survival (OS), progression-free survival (PFS), disease-free survival (DFS), objective response rate (ORR), disease control rate (DCR), pathological complete response (pCR), and adverse events (AEs). The results of 30 RCTs containing 9655 patients showed limited benefits in celecoxib-combined cancer therapy. However, celecoxib-combined palliative therapy prolonged PFS in epidermal growth factor receptor (EGFR) wild-type patients (HR = 0.57, 95%CI = 0.35-0.94). Moreover, despite a slight increase in thrombocytopenia (RR = 1.35, 95%CI = 1.08-1.69), there was no increase in other toxicities. Celecoxib combined with adjuvant therapy indicated a better OS (HR = 0.850, 95%CI = 0.725-0.996). Furthermore, celecoxib plus neoadjuvant therapy improved the ORR in standard cancer therapy, especially neoadjuvant therapy (overall: RR = 1.13, 95%CI = 1.03-1.23; neoadjuvant therapy: RR = 1.25, 95%CI = 1.09-1.44), but not pCR. Our study indicated that adding celecoxib to palliative therapy prolongs the PFS of EGFR wild-type patients, with good safety profiles. Celecoxib combined with adjuvant therapy prolongs OS, and celecoxib plus neoadjuvant therapy improves the ORR. Thus, celecoxib-combined cancer therapy may be a promising therapy strategy.

Postoperative Adjuvant Treatment Strategy for Locally Advanced Rectal Cancer after Neoadjuvant Treatment.

BACKGROUND: Neoadjuvant (chemo) radiotherapy is used as a standard treatment for locally advanced rectal cancer (LARC), but there is no general consensus on either the efficacy of postoperative adjuvant chemotherapy in patients with LARC after neoadjuvant treatment and surgery, or whether the addition of oxaliplatin to adjuvant chemotherapy provides survival benefits. METHODS: We performed a meta-analysis of data from the PubMed and Embase databases. We included patients with LARC who received neoadjuvant (chemo) radiotherapy and curative surgery. Overall survival (OS), disease-free survival (DFS), toxicity, and compliance were analyzed in the oxaliplatin/fluorouracil- (OX/FU-) based group compared with the FU-based group, and in the chemotherapy group compared with the observation group. RESULTS: Twenty studies were included in the analysis. Our results indicated that adjuvant chemotherapy prolonged OS (hazard ratio [HR] = 0.78, 95%CI = 0.67-0.91) in patients with LARC treated with neoadjuvant (chemo) radiotherapy and surgery compared with those in the observation group. Subgroup analysis showed the same results in both the ypStage II and ypStage III groups. Compared with those in the observation group, patients in the chemotherapy group also showed an increase in DFS (HR = 0.75, 95%CI = 0.60-0.93). No significant increase was observed in OS (HR = 1.04, 95%CI = 0.87-1.24) or DFS (HR = 0.98, 95%CI = 0.76-1.27) when oxaliplatin was added to FU-based adjuvant chemotherapy, as compared with the FU-based treatment, and subgroup analysis also indicated no survival benefits in the clinical stage II, clinical stage III, ypStage II, and ypStage III groups. CONCLUSIONS: For patients with LARC who have already received neoadjuvant (chemo) radiotherapy and curative surgery, adjuvant chemotherapy improves OS over that in the observation group. Adding oxaliplatin to FU-based adjuvant chemotherapy does not confer survival benefits beyond those from FU-based adjuvant chemotherapy.

Continuous Wound Infiltration with Local Anesthetic Is an Effective and Safe Postoperative Analgesic Strategy: A Meta-Analysis.

INTRODUCTION: Postoperative pain management is an essential module for perioperative care, especially for enhanced recovery after surgery programs. Continuous wound infiltration (CWI) with local anesthetic may be a promising postoperative analgesic strategy. However, its analgesic efficacy and safety remain debatable. METHODS: Embase and PubMed databases were systematically searched for relevant randomized controlled trials (RCTs). RCTs assessing the analgesic efficacy and safety of CWI with local anesthetic for postoperative analgesia were selected. The outcomes contained pain scores during rest and mobilization, total opioid consumption, time to the first request of rescue analgesia, length of hospital stay, satisfaction with analgesia, time to return of bowel function, postoperative nausea and vomiting, total complication, wound infection, hypotension, and pruritus. The weighted mean difference and risk ratio were used to pool continuous and dichotomous variables, respectively. RESULTS: A total of 121 RCTs were included. CWI with local anesthetic reduced postoperative pain during rest and mobilization at different time points, increased satisfaction with analgesia, shortened recovery of bowel function, and reduced postoperative nausea and vomiting compared with the placebo group, especially for laparotomy surgery. There were no significant differences in these clinical outcomes compared to epidural and intravenous analgesia. CWI with local anesthetic reduced the total opioid consumption and hypotension risk and did not increase total complications, wound infection, or pruritus. CWI with local anesthetic had a better analgesic efficacy without increased side effects for sternotomy surgery. However, CWI with local anesthetic did not translate into favorable analgesic benefits in laparoscopic surgery. CONCLUSION: CWI with local anesthetic is an effective postoperative analgesic strategy with good safety profiles in laparotomy and sternotomy surgery, and thus CWI with local anesthetic may be a promising analgesic option enhancing recovery after surgery programs for these surgeries.

Continuous wound infiltration (CWI) with local anesthetic may be a promising postoperative analgesic strategy, but its effect remains debatable. We performed this meta-analysis based on 121 high-quality articles (RCTs) to evaluate the analgesic efficacy and safety of CWI with local anesthetic. We found that CWI with local anesthetic could reduce postoperative pain, increase satisfaction with analgesia, shorten recovery of bowel function, and reduce postoperative nausea and vomiting, especially for laparotomy surgery. However, CWI with local anesthetic did not show favorable analgesic benefits in laparoscopic surgery.

Efficacy of immune checkpoint inhibitors and age in cancer patients.

Aim: To evaluate the impact of age on the efficacy of immune checkpoint inhibitors (ICI) in cancer patients. Materials & methods: The primary outcomes included overall survival (OS) and progression-free survival (PFS). Subgroup, meta-regression analysis and within-trial interaction HR were conducted. Results: A total of 34 studies containing 20,511 cancer patients were included. ICI could improve the OS and PFS in patient aged <65 and ≥65 years. Patients aged <75 years treated with ICI also had favorable OS and PFS compared with the control groups. Conclusion: ICI has comparable efficacy in cancer patients aged <65 and ≥65 years. Cancer patients aged ≥75 years need more attention in the future clinical trials.

Antibiotic use and the efficacy of immune checkpoint inhibitors in cancer patients: a pooled analysis of 2740 cancer patients.

The gut microbiota plays a critical role in the anti-tumor immune response. There is increasing data showing that antibiotics (ATBs) change the composition of the gut microbiota and affect the efficacy of immune checkpoint inhibitors (ICIs). However, this is the first meta-analysis to evaluate the association between ATB use and ICI efficacy in cancer patients to provide a better understanding of the strength of this association. We performed a literature search for relevant studies that evaluated the relationship between ATB use and ICI efficacy using the PubMed, Embase, and conference databases. The primary outcomes consisted of overall survival (OS) and progression-free survival (PFS) measured by hazard ratios (HR) and corresponding 95% confidence intervals (CI). Subgroup and sensitivity analyses were also performed. A total of 19 eligible studies comprising 2,740 cancer patients treated with ICIs were included in the analysis. Our results indicated that ATB use was negatively associated with OS in cancer patients (HR = 2.37; 95% CI = 2.05-2.75; P < .001), without heterogeneity (I2 = 0.0%; P = .851). Moreover, ATB use significantly reduced PFS in patients treated with ICIs (HR = 1.84; 95% CI = 1.49-2.26; P < .001; I2 = 56.2%). Similar results were obtained in the subgroup analyses stratified by the time of ATB use and cancer type. Sensitivity analyses confirmed the stability of our results. Therefore, the findings of our meta-analysis indicated that ATB use is negatively associated with OS and PFS in cancer patients treated with ICI immunotherapy.

Long non-coding RNA AB007962 is downregulated in gastric cancer and associated with poor prognosis.

A number of previous studies have reported that numerous long non-coding RNAs (lncRNAs) are dysregulated in gastric cancer (GC) and are involved in a series of biological and pathological processes. Total RNA was extracted from the cancerous tissues and matched normal adjacent tissues (NATs) of 96 patients with GC. The expression level of AB007962, a novel lncRNA, was determined by reverse transcription-quantitative polymerase chain reaction. The association between AB007962 expression levels and clinicopathological features were analyzed. Kaplan-Meier curves were also constructed in order to evaluate prognosis. Finally, publicly accessible data from The Cancer Genome Atlas was used to further verify the expression levels and clinical significance of AB007962. In conclusion, it was determined that the expression level of AB007962 was significantly reduced, compared with matched NATs in GC tissues (P=0.003). Survival analysis indicated that patients with intestinal-type GC with a reduced expression of AB007962 had a reduced prognosis, compared with those with an increased expression. AB007962 may be involved in the progression of GC and act as a novel prognostic biomarker for patients with GC, particularly in intestinal-type GC.

Non-coding RNAs participate in the regulatory network of CLDN4 via ceRNA mediated miRNA evasion.

Thousands of genes have been well demonstrated to play important roles in cancer progression. As genes do not function in isolation, they can be grouped into "networks" based on their interactions. In this study, we discover a network regulating Claudin-4 in gastric cancer. We observe that Claudin-4 is up-regulated in gastric cancer and is associated with poor prognosis. Claudin-4 reinforce proliferation, invasion, and EMT in AGS, HGC-27, and SGC-7901 cells, which could be reversed by miR-596 and miR-3620-3p. In addition, lncRNA-KRTAP5-AS1 and lncRNA-TUBB2A could act as competing endogenous RNAs to affect the function of Claudin-4. Our results suggest that non-coding RNAs play important roles in the regulatory network of Claudin-4. As such, non-coding RNAs should be considered as potential biomarkers and therapeutic targets against gastric cancer.Non-coding RNAs can modify the expression of proteins in cancer networks. Here the authors reveal a regulatory network in gastric cancer whereby claudin-4 expression is reduced by specific miRNAs, which are in turn bound by specific lncRNAs acting as competing endogenous RNAs (ceRNAs), resulting in increased claudin-4 expression.

Impact of age on efficacy of postoperative oxaliplatin-based chemotherapy in patients with rectal cancer after neoadjuvant chemoradiotherapy.

BACKGROUND: Clinical practice guidelines focusing on age-related adjuvant chemotherapy for rectal cancer are currently limited. The present study aimed to explore the impact of age on the efficacy of adjuvant oxaliplatin-based chemotherapy in patients with rectal cancer after neoadjuvant chemoradiotherapy. METHODS: We performed a retrospective cohort analysis using data from the Surveillance, Epidemiology, and End Results-Medicare-linked database from 1992-2009. We enrolled patients with yp stages I-III rectal cancer who received neoadjuvant chemoradiotherapy and underwent curative resection. The age-related survival benefit of adding oxaliplatin to adjuvant 5-fluorouracil (5-FU) chemotherapy was evaluated using Kaplan-Meier survival analysis with propensity score-matching and Cox proportional hazards models. RESULTS: Comparing the oxaliplatin group with the 5-FU group, there were significant interactions between age and chemotherapy efficacy in terms of overall survival (OS) (p for interaction = 0.017) among patients with positive lymph nodes (ypN+). Adding oxaliplatin to 5-FU could prolong survival in patients aged < 73 years and ypN+ category, and but did not translate into survival benefits in patients aged ≥ 73 years and ypN+ category. No significant interactions were observed among ypN- patients, and oxaliplatin did not significantly improve OS, regardless of age. CONCLUSIONS: In patients with rectal cancer who have already received neoadjuvant chemoradiotherapy and undergone curative resection, adding oxaliplatin to 5-FU could prolong OS in patients aged < 73 years and ypN+ category. However, adding oxaliplatin did not translate into survival benefits in patients age ≥ 73 years and ypN+ category, or in ypN- patients.

A novel long noncoding RNA-LOWEG is low expressed in gastric cancer and acts as a tumor suppressor by inhibiting cell invasion.

PURPOSE: Long noncoding RNA (lncRNA) have been reported to be involved in the development of multiple cancers. The aim of this study was to report the identification of lncRNA-CTD-2108O9.1, which we have named lncRNA low expressed in gastric cancer (lncRNA-LOWEG), and investigate its role in cancer development. METHODS: Total RNA was extracted from the tissues of 94 patients with GC, one normal gastric epithelial cell line and four GC cell lines. Expression levels of lncRNA-LOWEG were determined by real-time PCR. Moreover, CCK-8 proliferation assay, transwell cell invasion assay and flow cytometry were performed to study the effects of lncRNA-LOWEG on SGC-7901 cell proliferation, cell invasion and cell cycle progression. Lastly, western blot and real-time PCR were used to verify the potential target genes of lncRNA-LOWEG. RESULTS: Significantly reduced expression of lncRNA-LOWEG was found in gastric cancer tissues and cell lines (SGC-7901, AGS, BGC-823 and HG-27) compared with patient-matched nontumorous adjacent tissues (P < 0.01) or the normal gastric cell line GES-1 (P < 0.05). Moreover, the transwell assay showed that the number of cells capable of passing through the Matrigel was significantly reduced after lncRNA-LOWEG transfection (P < 0.05). However, lncRNA-LOWEG overexpression did not significantly influence cell proliferation (P > 0.05) and cell cycle progression (P > 0.05). Lastly, western blot and real-time PCR analysis suggested that lncRNA-LOWEG is positively correlated with the expression of leukemia inhibitory factor receptor (LIFR) gene at the translational level. CONCLUSIONS: LncRNA-LOWEG is a tumor suppressor that inhibits GC cell invasion. And LIFR gene is up-regulated by lncRNA-LOWEG.