Patterns of Expression of H2S-Producing Enzyme in Human Renal Cell Carcinoma Specimens: Potential Avenue for Future Therapeutics.

BACKGROUND: Renal cell carcinoma (RCC) is the most common cancer of the kidney. The most common histotype is clear-cell (cc) RCC. Hydrogen sulfide (H2S) is an angiogenic and anti-apoptotic gasotransmitter that is elevated under pseudohypoxic conditions. H2S is endogenously produced by three enzymes: Cystathionine γ-lyase (CSE), cystathionine ß-synthase (CBS), and 3-mercaptopyruvate sulfurtransferase (MPST). Seeing as increased expression of these enzymes has been observed in other human cancer types, this study aimed to quantify H2S-producing enzyme expression in human RCC samples and evaluate whether it correlated with clinical outcomes. PATIENTS AND METHODS: Eighty-eight human kidney tissue specimens, with healthy and cancerous tissue components, were immunohistochemically stained for CSE, CBS, and MPST. The mean pixel intensity of positively stained areas was quantified. A retrospective analysis was conducted to obtain patient demographics, rates of metastasis/recurrence, and prognostic characteristics. Statistical correlations between enzyme expressions and subsequent patient outcomes were evaluated. RESULTS: There was significantly greater expression of CSE, CBS, and MPST in cc-RCC compared to paired healthy tissue (p<0.0001). The difference in expression of CSE in cancerous versus normal tissue was significantly greater than that for CBS and MPST (p<0.0001 and p<0.01, respectively). Enzyme expression patterns in cancerous versus normal tissue did not correlate with nuclear grade, stage, histological type or cancer recurrence/metastasis. CONCLUSION: To our knowledge, this is the first report of the differential increase in expression of CSE, CBS, and MPST in human RCC. Although these patterns do not appear to correlate with cancer recurrence, metastasis, size or nuclear grade, their differential increase suggests a potential therapeutic target.

The impact of a muscle pump activator on incisional wound healing compared to standard stockings and compression devices in kidney and kidney-pancreas transplant recipients: A randomized controlled trial.

INTRODUCTION: We aimed to evaluate the impact of thrombo-embolic-deterrent + intermittent pneumatic compression (TED + IPC) vs. muscle pump activator (MPA) on incisional wound healing in kidney and simultaneous pancreas- kidney (SPK) transplant recipients. METHODS: We conducted a single-centre, randomized controlled trial in which 104 patients (kidney n=94; SPK n=10) were randomly assigned to wear TED + IPC (n= 52) or MPA (n=52) for the first six days following surgery. Patient demographics, postoperative outcomes, and incisional wound images were taken using a HIPAA-compliant application on postoperative days (POD) 3, 5, and 30, and assessed using the validated Southampton Wound Care Score. RESULTS: There were no demographic differences between the groups. The MPA group had a significant improvement in wound healing on POD 3 (p=0.04) that persisted until POD 5 (p=0.0003). At POD 30, both groups were similar in wound healing outcomes (p=0.51). Bayesian inferential analysis revealed that the use of TED + IPC following transplantation had inferior outcomes compared to the use of MPA with sequential moderate evidence. The rate of complex wound infections was significantly greater in the TED + IPC group compared to the MPA group (29% vs. 12%, respectively; p=0.03). Patients were more satisfied with the use of a MPA device than TED + IPC. No major complications were encountered in either group. CONCLUSIONS: The use of a MPA device in the immediate postoperative period leads to a significant improvement in immediate and early wound healing, and decreased number of complex wound infections following kidney and SPK transplantation compared to standard TED + IPC therapy. Patients were more satisfied with the use of a MPA device than TED + IPC.