Ureteric obstruction is frequently encountered in primary care urology and can lead to damage to the ipsilateral kidney. Relief of all types of obstruction generally leads to the normalization of any deterioration in renal function noted at diagnosis. However, some evidence from animal models suggests that obstruction can cause progressive deleterious effects on renal function and blood pressure control, especially in the presence of preexisting pathologies such as essential hypertension. The last 10 years have seen a proliferation of studies in rodents wherein complete unilateral ureteric obstruction has been used as a model of renal fibrosis. However, the relevance of the findings to human obstructive uropathy has, in many cases, not been the primary aim. In this review, we outline the major events linking damage to the renal parenchyma and cell death to the evolution of fibrosis following obstruction. Special focus is given to the role of apoptosis as a major cause of cell death during and post-complete ureteric obstruction. Several interventions that reduce tubular apoptosis are discussed in terms of their ability to prevent subsequent progression to end-organ damage and fibrosis.
Apoptosis and epithelial-mesenchymal transdifferentiation (EMT) occur in stressed tubular epithelial cells and contribute to renal fibrosis. Transforming growth factor (TGF)-beta(1) promotes these responses and we examined whether the processes were interdependent in vitro. Direct (caspase inhibition) and indirect [epidermal growth factor (EGF) receptor stimulation] strategies were used to block apoptosis during TGF-beta(1) stimulation, and the subsequent effect on EMT was assessed. HK-2 cells were exposed to TGF-beta(1) with or without preincubation with ZVAD-FMK (pan-caspase inhibitor) or concomitant treatment with EGF plus or minus preincubation with LY-294002 (PI3-kinase inhibitor). Cells were then assessed for apoptosis and proliferation by flow cytometry, crystal violet assay, and Western blotting. Markers of EMT were assessed by microscopy, immunofluorescence, real-time RT-PCR, Western blotting, PAI-1 reporter assay, and collagen gel contraction assay. TGF-beta(1) caused apoptosis and priming for staurosporine-induced apoptosis. This was blocked by ZVAD-FMK. However, ZVAD-FMK did not prevent EMT following TGF-beta(1) treatment. EGF inhibited apoptosis and facilitated TGF-beta(1) induction of EMT by increasing proliferation and accentuating E-cadherin loss. Additionally, EGF significantly enhanced TGF-beta(1)-induced collagen I gel contraction. EGF increased Akt phosphorylation during EMT, and the prosurvival effect of this was confirmed using LY-294002, which reduced EGF-induced Akt phosphorylation and reversed its antiapoptotic and proproliferatory effects. TGF-beta(1) induces EMT independently of its proapoptotic effects. TGF-beta(1) and EGF together lead to EMT. EGF increases proliferation and resistance to apoptosis during EMT in a PI3-K Akt-dependent manner. In vivo, EGF receptor activation may assist in the selective survival of a transdifferentiated, profibrotic cell type.
Compared to open surgery, robot-assisted hysterectomy offers benefits for reduced length of hospital stay and blood transfusions. The best evidence of improved outcomes is for simple total hysterectomy with node staging. Study quality was poor.
Objective Robot-assisted surgery is a recognised treatment for pelvic-organ prolapse. Many of the surgical subgroup outcomes for apical prolapse are reported together, leading to a paucity of homogenous data.Design Prospective observational cohort study (NCT01598467, clinicaltrials.gov) assessing outcomes for homogeneous subgroups of robot-assisted apical prolapse surgery.Setting Two European tertiary referral hospitals.Population Consecutive patients undergoing robot-assisted sacrocolpopexy (RASC) and supracervical hysterectomy with sacrocervicopexy (RSHS).Methods Anatomical cure (simplified Pelvic Organ Prolapse Quantification, sPOPQ, stage 1), subjective cure (symptoms of bulge), and quality of life (Pelvic Floor Impact Questionnaire, PFIQ-7).Main outcome measures Primary outcome: anatomical and subjective cure. Secondary outcomes: surgical safety and intraoperative variables.Results A total of 305 patients were included (RASC n = 188; RSHS n = 117). Twelve months follow-up was available for 144 (RASC 76.6%) and 109 (RSHS 93.2%) women. Anatomical success of the apical compartment occurred for 91% (RASC) and in 99% (RSHS) of the women. In all compartments, the success percentages were 67 and 65%, respectively. Most recurrences were in the anterior compartment [15.7% RASC (symptomatic 12.1%); 22.9% RSHS (symptomatic 4.8%)]. Symptoms of bulge improved from 97.4 to 17.4% (P < 0.0005). PFIQ-7 scores improved from 76.7 AE 62.3 to 13.5 AE 31.1 (P < 0.0005). The duration of surgery increased significantly for RSHS [183.1 AE 38.2 versus 145.3 AE 29.8 (P < 0.0005)]. Intraoperative complications and conversion rates were low (RASC, 5.3 and 4.3%; RSHS, 0.0 and 0.0%). Four severe postoperative complications occurred after RASC (2.1%) and one occurred after RSHS (1.6%).Conclusions This is the largest reported prospective cohort study on robot-assisted apical prolapse surgery. Both procedures are safe, with durable results.
Surgical technique varies widely despite the level of expertise and training. This study highlights the need for an evaluation of the effect of surgical technique on outcomes.
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