Efficacy and Safety of Preoperative Radiotherapy Versus Chemoradiotherapy in Advanced Rectal Cancer: A Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: This meta-analysis was conducted to evaluate the safety and efficacy of preoperative radiotherapy (RT) combined with surgery and preoperative chemoradiotherapy (CRT) combined with surgery for locally advanced rectal cancer. METHODS: PubMed, EMBASE and Cochrane Library were searched to collect published randomized controlled trials of preoperative radiotherapy or preoperative CRT combined with surgery for the treatment of locally advanced rectal cancer. Studies were screened according to inclusion and exclusion criteria, and quality was evaluated; RevMan 5.3 software was used for meta-analysis. RESULTS: In total, 7 related studies involving 3100 patients with locally advanced rectal cancer were evaluated. The pathological complete response rate, negative lymph node rate, R0 resection rate, and incidence of grade III/IV adverse reactions were lower in the RT group than in the CRT group. In the absence of postoperative chemotherapy, the 5-year local recurrence rate of RT was higher than that of CRT, but there was no significant difference between the groups among those who underwent postoperative chemotherapy. Moreover, there was no significant difference between the groups with regard to the 5-year survival rate, anal-preserving rate, or incidence of anastomotic leakage. CONCLUSION: Preoperative CRT is better than preoperative RT for the treatment of advanced rectal cancer, though the adverse reaction rate is higher.

Does a long interval between neoadjuvant chemoradiotherapy and surgery benefit the clinical outcomes of locally advanced rectal cancer? A systematic review and meta analyses.

PURPOSE: The study aims to systematically evaluate the clinical efficacy after 8 weeks (long interval, LI) between neoadjuvant chemoradiotherapy and surgery for locally advanced rectal cancer. METHODS: The PubMed database, EMBASE database, and the Cochrane Library (deadline: September 25, 2021) were searched to select clinical studies that compared two intervals between neoadjuvant chemoradiotherapy and surgery for locally advanced rectal cancer: after 8 weeks (long interval, LI) and within 8 weeks (short interval, SI). The included studies were screened and evaluated according to the inclusion and exclusion criteria, and meta-analysis was performed by RevMan 5.3 software. RESULTS: Eighteen studies were included, with 9070 cases in the LI group and 14,207 cases in the SI group. The analysis results showed that the pathologic complete response (PCR) rate in the LI group was higher than that in the SI group (P < 0.00001). There was no significant difference in the R0 resection rate (P = 0.85), anal preservation rate (P = 0.89), morbidity rate (P = 0.60), anastomotic leakage rate (P = 0.06), operation time (P = 0.58), local recurrence rate (P = 0.56), distant metastasis rate (P = 0.32), or overall survival (OS) rate (P = 0.17) between the two groups. CONCLUSION: A longer interval between neoadjuvant chemoradiotherapy and surgery can improve the PCR rate; however, it has no significant impact on the clinical efficacy or long-term prognosis. Due to some limitations in the number and quality of the studies, these findings still need to be further verified by multicenter, large-sample high-quality RCTs in the future.

Meta-analysis of mesh-plug repair and Lichtenstein repair in the treatment of primary inguinal hernia.

The present study systematically evaluated the clinical effects of mesh-plug and Lichtenstein herniorrhaphy in the treatment of primary inguinal hernia. PubMed, Embase, and the Cochrane Library (cut-off: May 25, 2020) databases were searched to select randomized controlled trials (RCTs) on mesh-plug and Lichtenstein herniorrhaphy for the treatment of primary inguinal hernia. Articles that met the inclusion criteria were screened and evaluated for quality. RevMan 5.3 software was used to perform a meta-analysis of operation time, discomfort in the inguinal region, haematoma, seroma, infection, time to return to normal activities, incidence of postoperative chronic pain, and recurrence rate. Eleven RCTs with 1457 patients in the mesh-plug group and 1472 in the Lichtenstein group were included. Meta-analysis showed that the mesh-plug herniorrhaphy group had a shorter operation time than the Lichtenstein herniorrhaphy group [P < 0.0001] but a longer time to return to normal activities after surgery [MD = 1.48, 95% CI (0.58, 2.38), P = 0.001]. There were no significant differences in postoperative discomfort in the inguinal region [P = 0.90], seroma [P = 0.10], haematoma [P = 0.27], infection [P = 0.40], incidence of postoperative chronic pain [P = 0.90], or recurrence rate [P = 0.77] between groups. Mesh-plug herniorrhaphy requires a shorter operation time than Lichtenstein herniorrhaphy, and there is no significant difference in postoperative complications or recurrence rate between the two methods. Clinical trial registration: INPLASY202070088. Meta-analysis of mesh -plug repair and Lichtenstein repair in the treatment of primary inguinal hernia.

Adenoid cystic carcinoma of the vagina: A case report.

RATIONALE: Squamous carcinoma is the most common malignancy of vagina. Adenoid cystic carcinoma (ACC) in the vagina is very rare. PATIENT CONCERNS: In the present study, we present a 45-year-old woman with a palpable swelling in the vagina. The patient reported body paresthesia, chest congestion, expiratory dyspnea, and itching in the thigh root. DIAGNOSIS: The ultrasound results revealed inhomogeneous echoes of the muscular layer in the middle and distal of the vagina, and probed a slightly richer blood flow signal. Then biopsy was performed. On microscopic examination, it was observed that tumor cells were arranged in a tubular or cribriform pattern, and exhibited a consistent size, small nuclei, and nuclear fission. The myoepithelium was lined around the glandular cavity, but the myoepithelium was tumorous. Immunohistochemistry was performed for further verification. Vimentin was positive in mesenchyme and CK-P was positive in epithelial cells. P63 and calponin were spotted, which were focal positive around the glandular cavity. Finally, the patient was diagnosed as ACC. INTERVENTIONS: At last, the patient chose chemoradiotherapy, not surgical excision. OUTCOMES: The patient is alive and well 13 months after the initial diagnosis. LESSONS: ACC in the vagina is extremely rare. To our knowledge, this report is the first case of ACC arising from the vagina in English-language literature. Extensive surgical section of the tumour and chemoradiotherapy are recommended for therapy. Because of rarity, the prognosis of ACC in vagina is not known.

CRIP1 promotes cell migration, invasion and epithelial-mesenchymal transition of cervical cancer by activating the Wnt/ß­catenin signaling pathway.

Cervical cancer (CC) is the third most common cancer and the fourth leading cause of malignancy-related mortality in women worldwide. In addition, epithelial-mesenchymal transition (EMT) has been generally studied in tumor metastasis researches in recent years. Cysteine-rich intestinal protein 1 (CRIP1) is differently expressed in human cancer cells. However, the role it plays in CC has not been revealed at present. Preliminary experiments have shown that CRIP1 had a higher expression in CC tissues, compared with adjacent noncancerous tissues. Real-time PCR and western blot were performed to analyze CRIP1 expression in CC cell lines. CRIP1 transient transfection vector and siRNA were constructed. Further analysis revealed the promotion effects of CRIP1 on the cell migration and invasion of CC in vitro (P < 0.01). In addition, western blot was performed to show that CRIP1 mediates EMT by means of EMT marker detection. The expression of CRIP1 and ߭catenin in CC tissues was analyzed by immunohistochemistry (IHC). Interestingly, CRIP1 and ߭catenin were both highly expressed in CC tissues (P < 0.01). Furthermore, CRIP1 increased the protein expression level of c-myc, cyclinD-1 and cytoplasmic ߭catenin, which are indicators for activating the Wnt/߭catenin signaling pathway. In conclusion, CRIP1 promotes cell migration and invasion, mediates EMT and activates the Wnt/߭catenin signaling pathway in CC.

Linking arsenite- and cadmium-generated oxidative stress to microsatellite instability in vitro and in vivo.

Mismatch repair (MMR) corrects replicative errors and minimizes DNA damage that occurs frequently in microsatellites. MMR deficiency is manifested as microsatellite instability (MSI), which contributes to hypermutability and cancer pathogenesis. Genomic instability, including MSI and chromosomal instability, appears to be responsible for the carcinogenesis of arsenic and cadmium, common contaminants in our environment. However, few studies have addressed arsenic- or cadmium-induced MSI, especially its potential link with arsenic- or cadmium-generated oxidative stress, due to the lack of quantifiable MSI assays and cost-effective animal models. Here, using a dual-fluorescent reporter, we demonstrate that sub-lethal doses of cadmium or arsenite, but not arsenate, increased the MSI frequency in human colorectal cancer cells. Arsenite- and cadmium-induced MSI occurred concomitantly with increased levels of reactive species and oxidative DNA damage, and with decreased levels of MMR proteins. However, N-acetyl-l-cysteine (NAC) suppressed arsenite- and cadmium-induced MSI and oxidative stress while restoring the levels of MMR proteins in the cells. Similarly, MSI was induced separately by arsenite and cadmium, and suppressed by NAC, in zebrafish in a fluorescinated PCR-based assay with newly-developed microsatellite markers and inter-segmental comparisons. Of five selected antioxidants examined, differential effects were exerted on the MSI induction and cytotoxicity of both arsenite and cadmium. Compared to MMR-proficient cells, MMR-deficient cells were more resistant to arsenic-mediated and cadmium-mediated cytotoxicity. Our findings demonstrate a novel linkage between arsenite-generated and cadmium-generated oxidative stress and MSI induction. Our findings also caution that antioxidants must be individually validated before being used for preventing arsenite- and cadmium-induced MSI that is associated with cancer development.

Afatinib circumvents multidrug resistance via dually inhibiting ATP binding cassette subfamily G member 2 in vitro and in vivo.

Multidrug resistance (MDR) to chemotherapeutic drugs is a formidable barrier to the success of cancer chemotherapy. Expressions of ATP-binding cassette (ABC) transporters contribute to clinical MDR phenotype. In this study, we found that afatinib, a small molecule tyrosine kinase inhibitor (TKI) targeting EGFR, HER-2 and HER-4, reversed the chemoresistance mediated by ABCG2 in vitro, but had no effect on that mediated by multidrug resistance protein ABCB1 and ABCC1. In addition, afatinib, in combination with topotecan, significantly inhibited the growth of ABCG2- overexpressing cell xenograft tumors in vivo. Mechanistic investigations exhibited that afatinib significantly inhibited ATPase activity of ABCG2 and downregulated expression level of ABCG2, which resulted in the suppression of efflux activity of ABCG2 in parallel to the increase of intracellular accumulation of ABCG2 substrate anticancer agents. Taken together, our findings may provide a new and useful combinational therapeutic strategy of afatinib with chemotherapeutical drug for the patients with ABCG2 overexpressing cancer cells.