Gastric carcinogenesis arises from complicated interactions among host, environmental and bacterial factors, which cause genetic and epigenetic dysregulation of oncogenic and tumor-suppressive genes. MicroRNAs (miRNAs), a class of small non-coding RNAs that post-transcriptionally regulate ~30% human genes, may serve as oncogenes or tumor-suppressors in malignancies, including gastric cancer (GC). Although miRNA dysregulation commonly exists in GC, exact roles miRNAs serve in the pathogenesis and promotion of this tumor remain undetermined. Recently, results of previous studies regarding mechanisms underlying miRNAs generally converged on pathways critical in cellular processes, including cell proliferation, apoptosis and invasion, among which phosphatase and tensin homolog (PTEN)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling is a fundamental one, with frequent oncogenic alterations in GC. Therefore, in the present review, the disorder and function of miRNAs and PTEN/PI3K/Akt signaling in GC are discussed. Additionally, how miRNAs transduce their effects by regulating this pathway, particularly in GC stem cells and the tumor microenvironment, and two novel hypotheses significant in carcinogenesis, tumor progression and recurrence, are discussed. Furthermore, the roles of miRNAs and the PTEN/PI3K/Akt pathway in target therapies against this lethal disease are outlined.
Ureteroplasty using onlay grafts or flaps emerged as an innovative procedure for the management of proximal and midureteral strictures. Autologous grafts or flaps used commonly in ureteroplasty include the oral mucosae, bladder mucosae, ileal mucosae, and appendiceal mucosae. Oral mucosa grafts, especially buccal mucosa grafts (BMGs), have gained wide acceptance as a graft choice for ureteroplasty. The reported length of BMG ureteroplasty ranged from 1.5 to 11 cm with success rates of 71.4%-100%. However, several studies have demonstrated that ureteroplasty using lingual mucosa grafts yields better recipient site outcomes and fewer donor site complications than that using BMGs. In addition, there is no essential difference in the efficacy and complication rates of BMG ureteroplasty using an anterior approach or a posterior approach. Intestinal graft or flap ureteroplasty was also reported. And the reported length of ileal or appendiceal flap ureteroplasty ranged from 1 to 8 cm with success rates of 75%-100%. Moreover, the bladder mucosa, renal pelvis wall, and penile/preputial skin have also been reported to be used for ureteroplasty and have achieved satisfactory outcomes, but each graft or flap has unique advantages and potential problems. Tissue engineering-based ureteroplasty through the implantation of patched scaffolds, such as the small intestine submucosa, with or without cell seeding, has induced successful ureteral regeneration structurally close to that of the native ureter and has resulted in good functional outcomes in animal models.
Long ureteral defects have remained a challenge to urologists for a long time. Bowel interposition, including ileal ureter, appendiceal interposition and reconfigured colon substitution, has gained wide acceptance, even though it is a complicated procedure and associated with some potential complications. Mucus obstruction and metabolic disorders are common complications of intestinal substitution. To circumvent these troubles, modified techniques, such as tapering the bowel graft, intestinal onlay flap and the Yang-Monti procedure, are used. In particular, Yang-Monti ileal ureter replacement is a highly effective option for ureteral reconstruction, and the incidence of complications would be significantly reduced in select patients. After being combined with the Boari flap or psoas hitch technique, the length of intestinal segment used can also be significantly reduced. Most recent long-term results suggest that ileal ureter replacement with antireflux anastomosis seems to be remarkably free of complications, and we highly praise the distal nipple valve technique. Appendiceal interposition is available for patients with normal appendix, and usually this procedure is limited to reconstructing the right ureter. Appendiceal onlay ureteroplasty has emerged as a feasible and effective option to manage patients with complex proximal and midureteral strictures of the right side. The colon is rarely used for ureteral reconstruction because of its large caliber and mucous surface area. However, a reconfigured colon segment is a good substitute to reconstruct long-segment ureteral defects, and longterm follow up confirmed minimal complications and improved renal function. This review provides a comprehensive perspective on complex ureteral reconstruction and replacement using intestinal segments, in particular, ileal ureter replacement.
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