Bilateral Peritoneal Flaps Reduce Incidence and Complications of Lymphoceles after Robotic Radical Prostatectomy with Pelvic Lymph Node Dissection-Results of the Prospective Randomized Multicenter Trial ProLy

Purpose: The purpose of this study was to investigate the effect of a surgically constructed bilateral peritoneal flap (PIF) as an adjunct to robot-assisted radical prostatectomy (RARP) and pelvic lymph node dissection (PLND) on the incidence of lymphoceles. Materials and Methods: A total of 530 men with localized prostate cancer underwent a RARP with bilateral extended standardized PLND in a prospective randomized controlled trial. In group A, a PIF was created by suturing the margins of the bladder peritoneum to the ipsilateral endopelvic fascia at 2 points on each side. In group B, no PIF was created. The patients were followed 30 and 90 days after the surgery to assess the incidence, extent and treatment of lymphoceles. Results: Lymphoceles occurred in 22% of group A patients and 33% of group B patients (p=0.008). Symptomatic lymphoceles were observed in 3.3% of group A patients and 8.1% of group B patients (p=0.027). Lymphoceles requiring intervention occurred significantly less frequently in group A patients (1.3%) than in group B patients (6.8%, p=0.002). The median lymphocele size was 4.3 cm in group A and 5.0 cm in group B (p=0.055). No statistically significant differences were observed in minor or major complications unrelated to lymphocele, blood loss, or surgical time between groups A and B. Conclusions: Bilateral PIFs in conjunction with RARP and PLND significantly reduce the total incidence of lymphoceles, the frequency of symptomatic lymphoceles and the rate of associated secondary interventions

High BMI and Surgical Time Are Significant Predictors of Lymphocele after Robot-Assisted Radical Prostatectomy

Lymphoceles (LC) occur in up to 60% after robot-assisted radical prostatectomy (RARP) and pelvic lymphadenectomy (PLND). In 2–10%, they are symptomatic and may cause complications and require treatment. Data on risk factors for the formation of lymphoceles after RARP and PNLD remain sparse in the urologic literature and are inconclusive to date. The underlying data of this secondary analysis were obtained from the prospective multi-center RCT ProLy. We performed a multivariate analysis to focus on the potential risk factors that may influence lymphocele formation. Patients with LC had a statistically significant higher BMI (27.8 vs. 26.3 kg/m2 , p < 0.001; BMI ≥ 30 kg/m2 : 31 vs. 17%, p = 0.002) and their surgical time was longer (180 vs. 160 min, p = 0.001) In multivariate analysis, the study group (control vs. peritoneal flap, p = 0.003), BMI (metric, p = 0.028), and surgical time (continuous, p = 0.007) were independent predictors. Patients with symptomatic lymphocele presented with higher BMI (29 vs. 26.6 kg/m2 , p = 0.007; BMI ≥ 30 kg/m2 : 39 vs. 20%, p = 0.023) and experienced higher intraoperative blood loss (200 vs. 150 mL, p = 0.032). In multivariate analysis, BMI ≥ 30 kg/m2 vs. < 30 kg/m2 was an independent predictor for the formation of a symptomatic lymphocele (p = 0.02). High BMI and prolonged surgical time are general risk factors for the development of LC. Patients with a BMI ≥ 30 kg/m2 had a higher risk for symptomatic lymphoceles

High BMI and Surgical Time Are Significant Predictors of Lymphocele after Robot-Assisted Radical Prostatectomy

Lymphoceles (LC) occur in up to 60% after robot-assisted radical prostatectomy (RARP) and pelvic lymphadenectomy (PLND). In 2–10%, they are symptomatic and may cause complications and require treatment. Data on risk factors for the formation of lymphoceles after RARP and PNLD remain sparse in the urologic literature and are inconclusive to date. The underlying data of this secondary analysis were obtained from the prospective multi-center RCT ProLy. We performed a multivariate analysis to focus on the potential risk factors that may influence lymphocele formation. Patients with LC had a statistically significant higher BMI (27.8 vs. 26.3 kg/m2, p 2: 31 vs. 17%, p = 0.002) and their surgical time was longer (180 vs. 160 min, p = 0.001) In multivariate analysis, the study group (control vs. peritoneal flap, p = 0.003), BMI (metric, p = 0.028), and surgical time (continuous, p = 0.007) were independent predictors. Patients with symptomatic lymphocele presented with higher BMI (29 vs. 26.6 kg/m2, p = 0.007; BMI ≥ 30 kg/m2: 39 vs. 20%, p = 0.023) and experienced higher intraoperative blood loss (200 vs. 150 mL, p = 0.032). In multivariate analysis, BMI ≥ 30 kg/m2 vs. 2 was an independent predictor for the formation of a symptomatic lymphocele (p = 0.02). High BMI and prolonged surgical time are general risk factors for the development of LC. Patients with a BMI ≥ 30 kg/m2 had a higher risk for symptomatic lymphoceles

Olfactory Receptors as Biomarkers in Human Breast Carcinoma Tissues

Olfactory receptors (ORs) are known to be expressed in a variety of human tissues and act on different physiological processes, such as cell migration, proliferation, or secretion and have been found to function as biomarkers for carcinoma tissues of prostate, lung, and small intestine. In this study, we analyzed the OR expression profiles of several different carcinoma tissues, with a focus on breast cancer. The expression of OR2B6 was detectable in breast carcinoma tissues; here, transcripts of OR2B6 were detected in 73% of all breast carcinoma cell lines and in over 80% of all of the breast carcinoma tissues analyzed. Interestingly, there was no expression of OR2B6 observed in healthy tissues. Immunohistochemical staining of OR2B6 in breast carcinoma tissues revealed a distinct staining pattern of carcinoma cells. Furthermore, we detected a fusion transcript containing part of the coding exon of OR2B6 as a part of a splice variant of the histone HIST1H2BO transcript. In addition, in cancer tissues and cell lines derived from lung, pancreas, and brain, OR expression patterns were compared to that of corresponding healthy tissues. The number of ORs detected in lung carcinoma tissues was significantly reduced in comparison to the surrounding healthy tissues. In pancreatic carcinoma tissues, OR4C6 was considerably more highly expressed in comparison to the respective healthy tissues. We detected OR2B6 as a potential biomarker for breast carcinoma tissues

Optimised photodynamic diagnosis for transurethral resection of the bladder (TURB) in German clinical practice: results of the noninterventional study OPTIC III

White light cystoscopy (WLC) is the standard procedure for visualising non-muscle invasive bladder cancer (NMIBC). However, WLC can fail to detect all cancerous lesions, and outcomes with transurethral resection of the bladder differ between institutions, controlled trials, and possibly between trials and routine application. This noninterventional study assessed the benefit of hexaminolevulinate blue light cystoscopy (HALC; Hexvix(A (R)), Ipsen Pharma GmbH, Germany) plus WLC versus WLC alone in routine use. From May 2013 to April 2014, 403 patients with suspected NMIBC were screened from 30 German centres to perform an unprecedented detailed assessment of the additional detection of cancer lesions with HALC versus WLC alone. Among the histological results for 929 biopsy samples, 94.3 % were obtained from suspected cancerous lesions under either WLC or HALC: 59.5 % were carcinoma tissue and 40.5 % were non-cancerous tissue. Of all cancer lesions, 62.2 % were staged as Ta, 20.1 % as T1, 9.3 % as T2, 7.3 % as carcinoma in situ (CIS), and 1.2 % were unknown. Additional cancer lesions (+6.8 %) and CIS lesions (+25 %, p 1 additional positive lesion was detected with HALC, and 2.2 % of NMIBC patients would have been missed with WLC alone. No adverse events were observed. The results of this study demonstrate that HALC significantly improves the detection of NMIBC versus WLC alone in routine clinical practice in Germany. While this benefit is statistically significant across all types of NMIBC, it seems most relevant in CIS

Characterization of the Olfactory Receptor OR10H1 in Human Urinary Bladder Cancer

Olfactory receptors (ORs) are a large group of G-protein coupled receptors predominantly found in the olfactory epithelium. Many ORs are, however, ectopically expressed in other tissues and involved in several diseases including cancer. In this study, we describe that one OR, OR10H1, is predominantly expressed in the human urinary bladder with a notably higher expression at mRNA and protein level in bladder cancer tissues. Interestingly, also significantly higher amounts of OR10H1 transcripts were detectable in the urine of bladder cancer patients than in the urine of control persons. We identified the sandalwood-related compound Sandranol as a specific agonist of OR10H1. This deorphanization allowed the functional characterization of OR10H1 in BFTC905 bladder cancer cells. The effect of receptor activation was morphologically apparent in cell rounding, accompanied by changes in the cytoskeleton detected by β-actin, T-cadherin and β-Catenin staining. In addition, Sandranol treatment significantly diminished cell viability, cell proliferation and migration and induced a limited degree of apoptosis. Cell cycle analysis revealed an increased G1 fraction. In a concentration-dependent manner, Sandranol application elevated cAMP levels, which was reduced by inhibition of adenylyl cyclase, and elicited intracellular Ca2+ concentration increase. Furthermore, activation of OR10H1 enhanced secretion of ATP and serotonin. Our results suggest OR10H1 as a potential biomarker and therapeutic target for bladder cancer

A double metachronous ureter metastasis following curative resection of rectal cancer

A malignant ureteral obstruction is most often due to primary tumors of the ureter. However, it can occur secondary due to external tumor compression or metastatic infiltration. Distant metastases to the ureter are extremely rare. We present a case of a rare double distant metachronic metastasis to the right ureter as well as to the right renal pelvis in a 58-year-old female with a history of anterior resection for rectal cancer 2 years earlier. She presented with recurrent urinary tract infection and right hydronephrosis caused by an ureteral mass. The patient underwent a right nephroureterectomy via laparotomy. Two metastases of the rectal cancer in the ureteral mucosa were verified at histology. On account of the infiltration of the right ureteral orifice, a completion transurethral resection of the tumor was performed. A follow-up 3 and 6 months later showed no signs of tumor relapse and the patient was doing well. The differential diagnosis of malignant ureteral obstruction in patients with history of colorectal cancer should include the rare possibility of distant metastasis from the primary tumor

The activation of OR51E1 causes growth suppression of human prostate cancer cells

The development of prostate cancer (PCa) is regulated by the androgen-dependent activity of the androgen receptor (AR). Androgen-deprivation therapy (ADT) is therefore the gold standard treatment to suppress malignant progression of PCa. Nevertheless, due to the development of castration resistance, recurrence of disease after initial response to ADT is a major obstacle to successful treatment. As G-protein coupled receptors play a fundamental role in PCa physiology, they might represent promising alternative or combinatorial targets for advanced diseases. Here, we verified gene expression of the olfactory receptors (ORs) OR51E1 [prostate-specific G-protein coupled receptor 2 (PSGR2)] and OR51E2 (PSGR) in human PCa tissue by RNA-Seq analysis and RT-PCR and elucidated the subcellular localization of both receptor proteins in human prostate tissue. The OR51E1 agonist nonanoic acid (NA) leads to the phosphorylation of various protein kinases and growth suppression of the PCa cell line LNCaP. Furthermore, treatment with NA causes reduction of androgen-mediated AR target gene expression. Interestingly, NA induces cellular senescence, which coincides with reduced E2F1 mRNA levels. In contrast, treatment with the structurally related compound 1-nonanol or the OR2AG1 agonist amyl butyrate, neither of which activates OR51E1, did not lead to reduced cell growth or an induction of cellular senescence. However, decanoic acid, another OR51E1 agonist, also induces cellular senescence. Thus, our results suggest the involvement of OR51E1 in growth processes of PCa cells and its impact on AR-mediated signaling. These findings provide novel evidences to support the functional importance of ORs in PCa pathogenesis

Image_3_Characterization of the Olfactory Receptor OR10H1 in Human Urinary Bladder Cancer.JPEG

<p>Olfactory receptors (ORs) are a large group of G-protein coupled receptors predominantly found in the olfactory epithelium. Many ORs are, however, ectopically expressed in other tissues and involved in several diseases including cancer. In this study, we describe that one OR, OR10H1, is predominantly expressed in the human urinary bladder with a notably higher expression at mRNA and protein level in bladder cancer tissues. Interestingly, also significantly higher amounts of OR10H1 transcripts were detectable in the urine of bladder cancer patients than in the urine of control persons. We identified the sandalwood-related compound Sandranol as a specific agonist of OR10H1. This deorphanization allowed the functional characterization of OR10H1 in BFTC905 bladder cancer cells. The effect of receptor activation was morphologically apparent in cell rounding, accompanied by changes in the cytoskeleton detected by β-actin, T-cadherin and β-Catenin staining. In addition, Sandranol treatment significantly diminished cell viability, cell proliferation and migration and induced a limited degree of apoptosis. Cell cycle analysis revealed an increased G1 fraction. In a concentration-dependent manner, Sandranol application elevated cAMP levels, which was reduced by inhibition of adenylyl cyclase, and elicited intracellular Ca²⁺ concentration increase. Furthermore, activation of OR10H1 enhanced secretion of ATP and serotonin. Our results suggest OR10H1 as a potential biomarker and therapeutic target for bladder cancer.</p