Our results indicate a strong association between LVH and enhanced expression levels of FGF23, FGFR4 and calcineurin, activation of NFAT and reduced levels of soluble Klotho in the myocardium of patients with CKD. These alterations are not observed in kidney transplant patients.
Background: Post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) plays a crucial role in treatment of metastatic non-seminomatous germ cell cancer.Objective: To evaluate the functional outcome regarding the preservation of ejaculatory function comparing a bilateral vs. unilateral template resection in PC-RPLND patients. In addition, oncological safety and perioperative complications of the unilateral template resection was compared to the full bilateral one.Design/Setting/Participants: Between 2003 and 2018, 504 RPLNDs have been performed in 434 patients. The database of consecutive patients was queried to identify 171 patients with PC-RPLND after 1st line chemotherapy for a non-seminoma with or without bilateral template resection. Re-Do's, late relapse, salvage patients, and thoraco-abdominal approaches were excluded. Indication for a template resection was a unilateral residual mass mainly <5 cm as published (1).Outcome, Measurement, and Statistical Analysis: Descriptive statistics were used to report preoperative features, postoperative outcomes and patterns of recurrence, on the overall population and after stratification for the type of resection (bilateral vs. unilateral). Kaplan-Meier analyses were used to describe recurrence- and cancer-specific mortality-free survival rates at different time points.Results and Limitations: Overall, 90 and 81 patients underwent unilateral and bilateral radical resection, respectively. Median size of residual mass was 7 cm for bilateral and 4 cm for unilateral template resection. Clinical stage II and III were present in 31 and 69% of patients, respectively. Median follow-up was 14.5 months (IQR 3.3–37.6). The 1- and 2-year recurrence-free survival rates were 91 and 91%, and 77 and 72% for patients treated with unilateral template and bilateral resection, respectively (p = 0.0078). Median time to recurrence was 9.5 and 9 months in template and bilateral resection group, respectively.Adjunctive procedures were performed in 56 patients (33%) and were significantly more frequent in the bilateral resection group (43 vs. 23%, p = 0.006). The overall high-grade complication rate (Clavien-Dindo ≥ III) was 6, 3, and 9% in unilateral template and bilateral resection group, respectively (p = 0.6). The rate of preservation of antegrade ejaculation was significantly higher in the unilateral group.Conclusions: Antegrade ejaculation in patients undergoing unilateral template resection with a residual mass <5 cm can be preserved at a much higher rate. Moreover, this surgical procedure is oncologically safe in terms of mid-term recurrence and CSM-free survival rates. This data undermines the growing evidence of limited PC-RPLND being justifiable in strictly unilateral residual mass <5 cm. This data has to be confirmed with a longer follow-up regarding in-field and retroperitoneal recurrences.
507 Background: We thought to evaluate progression-free survival of stage II A/B seminoma patients (pts) undergoing primary retroperitoneal lymph node dissection (RPLND) without adjuvant treatment. Aim is to present interim data of a feasibility study and a phase II trial. Methods: Prior to the phase II study, 9 patients have been treated within a pilot feasibility study. After IRB approval, additional 12 patients from 3/2016 to 9/2018 within the prospective phase II trial were accrued. All patients received primary retroperitoneal lymph node dissection (open or daVinci assisted) for stage IIA/B seminoma without adjuvant treatment. The data was analyzed for peri- and postoperative outcome including recurrence free survival. The trial will have to accrue 30 pts and was designed to exclude a > 30% recurrence to standard treatment. Results: Since 5.2014 twenty-two patients with seminomateous germ cell tumor have been included in both studies, including one patient with an atypical inguinal recurrence and one patient with a 6 cm marker negative recurrence (clinical stage IIC). Primary RPLND was performed in 4 patients with initial CSIIA. 14 and 4 patients experiences a recurrence under surveillance and after carboplatin adjuvant treatment, respectively. Mean tumor size was 2.6 cm with a mean OR time of 134 min and a mean blood loss of 70 cc. One patient after DaVinci RPLND developed a ureteral stricture requiring ileal ureter substitute. The mean follow-up is 24 month (range 1-51 months), 17/22 patients (77%) are free of recurrence. 5/22 (23%) developed a recurrence (4x outside field and 1x inside field) with a mean time to recurrence of 4.5 months. All patients received salvage treatment (4x CTX and 1x radiotherapy) and are currently recurrence free. Conclusions: Primary RPLND in stage IIA/B seminoma patients is an experimental treatment approach in order to reduce long term toxicity and secondary malignancies. Interim results of this strategy justifies continuation of the study. This kind of surgery should only be performed within clinical trials in high volume referral centers. Clinical trial information: NCT 2015053664.
BackgroundDetection of circulating tumor cells (CTC) by techniques based on epithelial cell adhesion molecule (EpCAM) is suboptimal in urothelial carcinoma (UC). As HER2 is thought to be broadly expressed in UC, we explored its utility for CTC detection.MethodsHER2 and EpCAM expression was analyzed in 18 UC cell lines (UCCs) by qRT‐PCR, western blot and fluorescence‐activated cell scanning (FACS) and compared to the strongly HER2‐expressing breast cancer cell line SKBR3 and other controls. HER2 expression in UC patient tissues was measured by qRT PCR and correlated with data on survival and risk for metastasis. UCCs with high EpCAM and variable HER2 expression were used for spike‐in experiments in the CellSearch system. Twenty‐one blood samples from 13 metastatic UC patients were analyzed for HER2‐positive CTCs with CellSearch.ResultsHER2 mRNA and protein were broadly expressed in UCC, with some heterogeneity, but at least 10‐fold lower than in the HER‐2+ SKBR3 cells. Variations were unrelated to cellular phenotype or clinicopathological characteristics. EpCAM expression was essentially restricted to UCCs with epitheloid phenotypes. Heterogeneity of EpCAM and HER2 expression was observed also in spike‐in experiments. The 7 of 21 blood samples from 6 of 13 patients were enumerated as CTC positive via EpCAM, but only one sample stained weakly positive (1+) for HER2.ConclusionsDetection rate of CTCs by EpCAM in UC is poor, even in metastatic patients. Because of its widespread expression, particularly in patients with high risk of metastasis, detection of HER2 could improve identification of UC CTCs, which is why combined detection using antibodies for EpCAM and HER2 may be beneficial.
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