Psoas hitch procedure in 166 adult patients: The largest cohort study before the laparoscopic era.

Objectives: To present the short-term and long-term outcomes of the psoas hitch procedure in a large cohort with long-term follow-up. Patients and methods: A multicenter, retrospective cohort study was conducted. Patients were included if they had undergone an open psoas hitch procedure with ureteral reimplantation for different types of distal ureteral pathology between 1993 and 2017. Clinical failure was defined as radiologically-proven obstruction of the ureteroneocystostomy and/or post-operative complaints requiring additional surgery. Pre-operative demographic data and post-operative radiological imaging were collected. Complications were categorized as peri-operative, acute (<30 days), and long-term complications. Results: A total of 166 patients had undergone a psoas hitch procedure, with a median follow-up of 15 months (IQR 6-45). Indications for the procedure included intra-operative injury of the ureter during gynecological, urological or general surgery, transitional cell carcinoma of the distal ureter, fistulae, (radiation) fibrosis, and trauma. There was no significant difference in pre- and post-operative estimated glomerular filtration rate. Post-operative complications included urinary leakage, recurrent urinary tract symptoms, recurrent malignancy, and kidney failure. Postoperative imaging was available in 143 patients. Failure of the psoas hitch procedure was seen in 8% (11/143) of the patients. In 55% (6/11) of these patients, radiation fibrosis was the indication for the psoas hitch procedure. Conclusion: This study provides greater insight into the long-term complications of the open psoas hitch procedure in adults. The psoas hitch procedure can be considered a safe procedure for restoring the continuity of the ureter for different types of ureteral pathologies in adult patients. However, patients with a history of radiation therapy causing retroperitoneal fibrosis might be more prone to failure after the procedure.

E17K substitution in AKT1 in prostate cancer.

BACKGROUND: The phosphatidylinositol 3-kinase (PI3K)-AKT pathway is activated in many cancers. Mutational hotspots in AKT1 and in the regulatory and catalytic subunits of PI3K have been detected in multiple tumour types. In AKT1, the E17K substitution leads to a PI3K-independent activation of AKT1. METHODS: A mutational profiling of AKT1 and of the mutational hotspots in PIK3CA and PIK3R1 was carried out in samples from primary and recurrent prostate tumours. RESULTS: We show that, in prostate cancer, AKT1(E17K) had a prevalence of 1.4%. The mutation seemed to be associated with a favourable clinical course but it was not associated with a specific tumour growth pattern. Activating mutations in PIK3CA or PIK3R1 were not found in prostate cancer. CONCLUSION: The E17K substitution in AKT1 is rare in prostate cancer. It seems associated with a favourable clinical outcome but not with a specific histology of the tumour.

When to start cytotoxic therapy in asymptomatic patients with hormone refractory prostate cancer?

Until the publication of two pivotal trials, there were no treatment options available that did prolong the overall survival in men with hormone refractory prostate cancer (HRPC). Currently, docetaxel-based cytotoxic treatment is considered as a standard of care in all the patients with progressive metastatic HRPC. The use of this treatment regimen renders an equal survival benefit in all the subgroups of patients; however, there is a substantial difference in the overall survival between the subgroups. This review addresses the optimal timing of the cytotoxic treatment in asymptomatic patients with HRPC.

The PTEN gene in locally progressive prostate cancer is preferentially inactivated by bi-allelic gene deletion.

PTEN is frequently inactivated during the development of many cancers, including prostate cancer, and both bi-allelic and mono-allelic PTEN inactivation may contribute to tumorigenesis. PTEN mutations in clinical cancer specimens can easily be recorded but mono- or bi-allelic gene deletions are often difficult to assess. We performed a comprehensive study to detect PTEN inactivation in 40 locally progressive clinical prostate cancer specimens obtained by transurethral resection of the prostate, utilizing a variety of complementary technical approaches. The methods to detect PTEN deletion included allelotype analysis, dual-colour FISH and array-based CGH. We also applied a novel semi-quantitative approach, assessing the PTEN-WT (wild-type): PTEN-Psi (pseudogene) ratio (WPR). Structural analysis of PTEN was performed by single-strand conformational polymorphism (PCR-SSCP) and sequencing. PTEN protein expression was assessed by immunohistochemistry. Our data predict complete PTEN inactivation in 12 samples (30%), nine of these by bi-allelic deletion. Loss of one PTEN copy was also detected by several methodologies but the number could not be accurately assessed. Immunohistochemistry indicated the absence of PTEN protein in 15 samples, and heterogeneous expression of the protein in eight tumours. Taken together, these data show that bi-allelic deletion is a major mechanism of PTEN inactivation in locally progressive prostate cancer.

Prognostic factors in localised prostate cancer with emphasis on the application of molecular techniques.

Prostate cancer is the most prevalent malignancy in males in the Western world and the second leading cause of male cancer death. Prostate specific antigen (PSA) based screening and case finding leads to identification of early stage prostate cancer. It is often difficult to discriminate between patients that need curative treatment and those that can be managed conservatively. Prognostic factors are used to make this clinical decision. Based on the classification proposed by the American College of Pathologists and the World Health Organisation, selected prognostic factors in prostate cancer are described. Clinical applicable factors are stage, grade and serum PSA. Prognostic factors that are not routinely used (for various reasons) are ploidy, histological type and cancer volume in needle biopsies. All other factors (including circulating tumour cells, angiogenesis, growth factors, proliferation rate, apoptosis, nuclear morphometry, neuroendocrine differentiation, loss of chromosomal regions, tumour suppresser genes and adhesion molecules) are promising as prognostic factor although currently their use in clinical decisions is not recommended. The role of these factors in prostate cancer growth and their predictive value are discussed. The rapid developments in molecular techniques allow assessment of structure or function of thousands of genes in a prostate biopsy sample. We expect that molecular characterisation of tumour material will become a clinically important tool to predict prognosis in patients with localised prostate cancer.