Risk factors for lateral pelvic lymph node metastasis in patients with lower rectal cancer: a systematic review and meta-analysis.

Background and objective: Lateral pelvic lymph node (LPLN) metastasis is one of the prominent reasons for local recurrence (LR) in patients with rectal cancer (RC). The evaluation criteria of lateral lymph node dissection (LLND) for patients in eastern (mainly in Japan) and western countries have been controversial. The aim of this study was to analyse the risk factors for LPLN metastasis in order to guide surgical methods. Methods: We searched relevant databases (Embase (Ovid), Medline (Ovid), PubMed, Cochrane Library, and Web of Science) for articles published between 1 January 2000 and 05 October 2022 to evaluate the risk factors for LPLN metastasis in patients with RC in this meta-analysis. Results: A total of 24 articles with 5843 patients were included in this study. The overall results showed that female sex, age <60 years, pretherapeutic CEA level >5 ng/ml, clinical T4 stage (cT4), clinical M1 stage (cM1), distance of the tumour from the anal verge (AV) <50 mm, tumour centre located below the peritoneal reflection (Rb), short axis (SA) of LPLN ≥8 mm before nCRT, short axis (SA) of LPLN ≥5 mm after nCRT, border irregularity of LPLN, tumour size ≥50 mm, pathological T3-4 stage (pT3-4), pathological N2 stage (pN2), mesorectal lymph node metastasis (MLNM), lymphatic invasion (LI), venous invasion (VI), CRM (+) and poor differentiation were significant risk factors for LPLN metastasis (P <0.05). Conclusion: This study summarized almost all potential risk factors of LPLN metastasis and expected to provide effective treatment strategies for patients with LRC. According to the risk factors of lateral lymph node metastasis, we can adopt different comprehensive treatment strategies. High-risk patients can perform lateral lymph node dissection to effectively reduce local recurrence; In low-risk patients, we can avoid overtreatment, reduce complications and trauma caused by lateral lymph node dissection, and maximize patient survival and quality of life.

Comparison of the prognosis of four different surgical strategies for proximal gastric cancer: a network meta-analysis.

BACKGROUND: There is controversy regarding the long-term prognosis and short-term postoperative complications of different surgical strategies for proximal gastric cancer (PGC). METHODS: We searched for articles published in Embase (Ovid), Medline (Ovid), PubMed, Cochrane Library, and Web of Science between January 1, 1990, and February 1, 2021. We screened out the literature comparing different surgical strategies. We then evaluated the long-term and short-term outcome of different surgical strategies using a network meta-analysis, which summarizes the hazard ratio, odds ratio, mean difference, and 95% confidence interval. RESULTS: There were no significant differences between different surgical strategies for 5-year overall survival (OS), anastomotic leakage, or weight loss after 1 year. Compared with total gastrectomy with Roux-en-Y reconstruction (TG-RY) and proximal gastrectomy with double tract reconstruction (PG-DTR), the proximal gastrectomy with esophagogastrostomy (PG-EG) strategy significantly increased the incidence of reflux esophagitis; and the operation time and blood loss of the PG-EG strategy were significantly less than those of the other surgical strategies. The anastomotic stenosis rates of the PG-EG and proximal gastrectomy with jejunum interstitial (PG-JI) strategies were significantly higher than those of TG-RY and PG-DTR; the hemoglobin level after 1 year for the PG-DTR strategy was significantly higher than that of the TG-RY strategy. CONCLUSION: Our comprehensive literature research found that different surgical strategies had no significant difference in the long-term survival of PGC, but the incidence of reflux esophagitis and anastomotic stenosis after PG-DTR and TG-RY was significantly reduced.

Co-Delivery of Paclitaxel and shMCL-1 by Folic Acid-Modified Nonviral Vector to Overcome Cancer Chemotherapy Resistance.

Acquired chemoresistance presents a major clinical impediment, which is an urgent problem to be solved. Interestingly, myeloma cell leukemia-1 (MCL-1) and folate receptor expression levels are higher in chemotherapy-resistant patients than in pretreatment patients. In this study, a multifunctional folic acid (FA)-targeting core-shell structure is presented for simultaneous delivery of shMCL-1 and paclitaxel (PTX). The transfection efficiency of shMCL-1 with the FA-targeting delivery system is higher than with a nontargeting delivery system in Skov3 and A2780T cells. The FA-targeting system significantly inhibits cell growth, blocks cell cycles, and promotes apoptosis of cancer cells in vitro. The mechanisms involved in inhibiting growth are related to Bcl-2/Bax and cdc2/Cyclin B1 pathways. An analysis of RNA sequencing suggests that shMCL-1 reverses chemoresistance through regulating genes such as regulator of chromosome condensation 2 (RCC2). The synergetic effect of shMCL-1 and PTX effectively inhibits tumor growth in both PTX-resistant and normal cancer models by inducing tumor apoptosis, inhibiting proliferation, and limiting tumor angiogenesis. The study results indicate that a FA-targeting delivery system combining shMCL-1 with PTX can simultaneously target tumor sites and restore the sensitivity of chemotherapy-resistant cancer to PTX. These findings have important implications for patients with normal or PTX-resistant cancer.

Comparison of the prognosis of four different treatment strategies for acute left malignant colonic obstruction: a systematic review and network meta-analysis.

BACKGROUND: There is controversy regarding the efficacy of different treatment strategies for acute left malignant colonic obstruction. This study investigated the 5-year overall survival (OS) and disease-free survival (DFS) of several treatment strategies for acute left malignant colonic obstruction. METHODS: We searched for articles published in PubMed, Embase (Ovid), MEDLINE (Ovid), Web of Science, and Cochrane Library between January 1, 2000, and July 1, 2020. We screened out the literature comparing different treatment strategies. Evaluate the primary and secondary outcomes of different treatment strategies. The network meta-analysis summarizes the hazard ratio, odds ratio, mean difference, and its 95% confidence interval. RESULTS: The network meta-analysis involved 48 articles, including 8 (randomized controlled trials) RCTs and 40 non-RCTs. Primary outcomes: the 5-year overall survival (OS) and disease-free survival (DFS) of the CS-BTS strategy and the DS-BTS strategy were significantly better than those of the ES strategy, and the 5-year OS of the DS-BTS strategy was significantly better than that of CS-BTS. The long-term survival of TCT-BTS was not significantly different from those of CS-BTS and ES. SECONDARY OUTCOMES: compared with emergency resection (ER) strategies, colonic stent-bridge to surgery (CS-BTS) and transanal colorectal tube-bridge to surgery (TCT-BTS) strategies can significantly increase the primary anastomosis rate, CS-BTS and decompressing stoma-bridge to surgery (DS-BTS) strategies can significantly reduce mortality, and CS-BTS strategies can significantly reduce the permanent stoma rate. The hospital stay of DS-BTS is significantly longer than that of other strategies. There was no significant difference in the anastomotic leakage levels of several treatment strategies. CONCLUSION: Comprehensive literature research, we find that CS-BTS and DS-BTS strategies can bring better 5-year OS and DFS than ER. DS-BTS strategies have a better 5-year OS than CS-BTS strategies. Without considering the hospital stays, DS-BTS strategy is the best choice.

Co-Delivery of Docetaxel and Curcumin via Nanomicelles for Enhancing Anti-Ovarian Cancer Treatment.

INTRODUCTIONS: Ovarian cancer is a stubborn malignancy of gynecological system with a high mortality rate. Docetaxel (DTX), the second-generation of anti-tumor drug Taxane, has shown superior efficacy over classic paclitaxel (PTX) in certain cancers. However, its clinical application is hindered by poor bioavailability. The natural spice extract curcumin (Cur) has been discovered to improve the bioavailability of DTX. Therefore, it is meaningful to develop a combined drug strategy of DTX and Cur with methoxy poly (ethylene glycol)-poly (L-lactic acid) (MPEG-PLA) copolymers in ovarian cancer therapy. METHODS: Injectable DTX-Cur/M nanomicelles were synthesized and characterized in the study. The molecular interactions between DTX, Cur and copolymer were simulated and the drug release behavior was investigated. The anti-tumor activity and anti-tumor mechanisms of DTX-Cur/M were evaluated and explored in both cells and mice model of xenograft human ovarian cancer. RESULTS: DTX-Cur/M nanomicelles with an average particle size of 37.63 nm were obtained. The drug release experiment showed sustained drug release from DTX-Cur/M nanomicelles. The MTT assay and apoptotic study indicated that DTX-Cur/M exhibited stronger inhibition and pro-apoptotic effects on A2780 cells compared with DTX or Cur alone. In vivo anti-tumor experiment results confirmed that the DTX-Cur/M played the most effective role in anti-ovarian cancer therapy by inhibiting tumor proliferation, suppressing tumor angiogenesis and promoting tumor apoptosis. CONCLUSION: We designed injectable DTX-Cur/M nanomicelles for co-delivery of DTX and Cur agents to the tumor site through systemic administration. The DTX-Cur/M nanomicelle would be a biodegradable, sustainable and powerful anti-tumor drug candidate with great potential in ovarian cancer treatment.

Synergetic therapy of glioma mediated by a dual delivery system loading α-mangostin and doxorubicin through cell cycle arrest and apoptotic pathways.

Two of the biggest hurdles in the deployment of chemotherapeutics against glioma is a poor drug concentration at the tumor site and serious side effects to normal tissues. Nanocarriers delivering different drugs are considered to be one of the most promising alternatives. In this study, a dual delivery system (methoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL)) loaded with α-mangostin (α-m) and doxorubicin (Dox) was decorated and constructed by self-assembly to determine its ability to treat glioma. Molecular dynamics simulations showed that MPEG-PCL could provide ideal interaction positions for both α-m and Dox, indicating that the two drugs could be loaded into MPEG-PCL. Based on the in vitro results, MPEG-PCL loaded with α-m and Dox (α-m-Dox/M) with a size of 25.68 nm and a potential of -1.51 mV was demonstrated to significantly inhibit the growth and promote apoptosis in Gl261, C6 and U87 cells, and the effects of the combination were better than each compound alone. The mechanisms involved in the suppression of glioma cell growth were blockage of the cell cycle in S phase by inhibition of CDK2/cyclin E1 and promotion of apoptosis through the Bcl-2/Bax pathway. The synergetic effects of α-m-Dox/M effectively inhibited tumor growth and prolonged survival time without toxicity in mouse glioma models by inducing glioma apoptosis, inhibiting glioma proliferation and limiting tumor angiogenesis. In conclusion, a codelivery system was synthesized to deliver α-m and Dox to the glioma, thereby suppressing the development of glioma by the mechanisms of cell cycle arrest and cellular apoptosis, which demonstrated the potential of this system to improve the chemotherapy response of glioma.