Gender differences in clinicopathological features and survival in surgically treated patients with renal cell carcinoma: an analysis of the multicenter CORONA database

Purpose

To investigate gender differences in clinicopathological features and to analyze the prognostic impact of gender in renal cell carcinoma (RCC) patients undergoing surgery.

Methods

A total of 6,234 patients (eleven centers; Europe and USA) treated by radical or partial nephrectomy were included in this retrospective study (median follow-up 59 months; IQR 30–106). Gender differences in clinicopathological parameters were assessed. Multivariable Cox regression models were applied to determine the influence of parameters on disease-specific survival (DSS) and overall survival (OS).

Results

A total of 3,751 patients of the study group were male patients (60.2 %), who were significantly younger at diagnosis and received more frequently NSS than women. Significantly, more often high-grade tumors and simultaneous metastasis were present in men. Whereas tumor size and pTN stages did not differ between genders, clear-cell and chromophobe RCC was diagnosed less frequently, but papillary RCC more often in men. Gender also independently influenced DSS (HR 0.75, p < 0.001) and OS (HR 0.80, p < 0.001) with a benefit for women. However, inclusion of gender in multivariable models did not significantly gain predictive accuracies (PA) for DSS (0.868–0.870, p = 0.628) and OS (0.775–0.777, p = 0.522). Furthermore, no significantly different DSS and OS rates were found in patients undergoing NSS.

Conclusions

This study demonstrates important gender differences in clinicopathological features and outcome of RCC patients with improved DSS and OS for women compared to men, even if solely patients with clear-cell RCC or M0-stage are taken into evaluation. However, inclusion of gender in multivariable models does not significantly gain PA of multivariable models.     

Outcomes of a bladder preservation technique in female patients undergoing pelvic exenteration surgery for advanced gynaecological tumours

Introduction and hypothesis

The purpose of the study was to report the feasibility of the bladder preservation technique (BPT) during pelvic exenteration for primary advanced gynaecological pelvic tumours (PRSGT) as an alternative for continent urinary diversion.

Methods

Sixteen consecutive female patients underwent BPT during PRSGT. Median age was 50.8 years (range 37–65). Tumours included cervical (5 patients), corpus/vaginal (9), and ovarian (2) carcinomas. In resectable tumours, the excision of the distal ureters and the posterior bladder wall with an inverted “V” incision into the trigone down to the vaginal wall was performed with bladder blood and nerve supply preservation. The remaining mobilized leaflets were fixed to the psoas muscle/sacral promontory. Average follow-up was 34 months (range 24–108). Follow-up parameters included postoperative continence grade (full [no pads], stress incontinence grade I [1–2 pads], and grade II [>2 pads]), urinary tract infections, micturation problems/residual urine, ureteric reflux as well as patients’ global satisfaction (PGS).

Results

All surgeries were done successfully. One patient developed a vesicovaginal fistula 4 weeks postoperatively and was managed conservatively. Fifteen patients (94 %) were able to empty their bladders postoperatively. Prolonged full continence was reported from 8 patients (50 %), incontinence grade I in 3 (18.8 %), and grade II in 5 (31.3 %). Two patients (incontinence grade II) developed cystoceles necessitating transvaginal bladder neck suspension with a fascia lata sling and were continent postoperatively. Another patient (6 %) underwent re-excision of a recurrent pelvic tumour necessitating intermittent self-catheterization. Postoperative hydronephrosis (grade I–II) was observed in 4 patients (25 %) and vesico-ureteral reflux (grade IV) in 4 (25 %) without the need for intervention. PGS and willingness to recommend their procedure to others were favourable.

Conclusions

In patients for whom complete bladder resection is not indicated for oncological reasons, BPT during PRSGT with ureteric reimplantation is feasible and safe and provides good functional results as well as patient global satisfaction. Lower tract surgeries could be safely carried out afterward. Long-term functional results support durable good PGS.     

The potential value of ultrasonography in the evaluation of carpal tunnel syndrome

The authors compared ultrasonography with electrophysiology for the diagnosis of carpal tunnel syndrome (CTS) on 110 clinically affected wrists. An increased cross sectional area in the proximal carpal tunnel larger than 0.11 cm(2) in combination with compression signs on longitudinal scans proved to be highly predictive for CTS (sensitivity, 89.1%; specificity, 98.0%). Ultrasound was comparable to electrophysiology in the diagnosis of CTS, and in 35% of cases changes in morphology suggested a specific therapeutic strategy.     

Cellular, Histomorphologic, and Clinical Characteristics of a New Octyl-2-Cyanoacrylate Skin Adhesive

Short-chained cyanoacrylates have been used for many years for topical skin closure. Toxic effects in cell culture of a new long-chained octyl-2-cyanoacrylate tissue adhesive are compared with those of short-chained ethyl-2- and butyl-2-cyanoacrylates. Two cellular tests were used: the agar overlay test and the MTT test. An in vitro test using copper plates coated with the three types of cyanoacrylates serves for evaluating the stability of polymerized skin adhesives. Bilateral neck skin incisions in Goettingen miniature pigs were glued on one side with Dermabond. On the other side, conventional sutures were applied. After the pigs were killed, the resulting skin samples were tested for the tensile strength of their wound stability. Samples of pig dermis were exemplarily and histomorphologically characterized. A clinical examination after submandibular lymph node dissection should examine the application in humans. Cell culture tests were used to show the toxic effects of the three cyanoacrylates. In a copper test, octyl-2-cyanoacrylate was more stabile than ethyl- and butyl-cyanoacrylates. Breaking strength was 30% lower 28 days after operation with the new product than with sutures. In electron microscopy, octyl-2-cyanoacrylate showed no disadvantages with regard to tissue regeneration and no histotoxicity. For plastic surgery, this new topical skin adhesive is a real alternative with attractive results, as compared with conventional suture.     

Folic acid reduces nuclear translocation of beta-catenin in rectal mucosal crypts of patients with colorectal adenomas

We have demonstrated that folic acid inhibits cell proliferation and epidermal growth factor receptor (EGFR) activation in colon cancer cell lines. We examined the effect of one year supplemental folic acid (5 mg/day) on the rectal mucosal expression of beta-catenin and pGSK3beta, known to be affected by EGF-R, in patients with colorectal adenomas. Folic acid treatment significantly reduced nuclear expression of beta-catenin (P < 0.05) and cellular expression of pGSK3beta (P < 0.01) when compared to placebo. Folic acid may exert its chemopreventive effect, at least in part, through inhibition of nuclear translocation of beta-catenin.     

Imaging-guided convection-enhanced delivery and gene therapy of glioblastoma

In a prospective phase I/II clinical study, we treated eight patients suffering from recurrent glioblastoma multiform with stereotactically guided intratumoral convection-enhanced delivery of an HSV-1-tk gene-bearing liposomal vector and systemic ganciclovir. Noninvasive identification of target tissue together with assessment of vector-distribution volume and the effects of gene therapy were achieved using magnetic resonance imaging and positron emission tomography. The treatment was tolerated well without major side effects. In two of eight patients, we observed a greater than 50% reduction of tumor volume and in six of eight patients focal treatment effects. Intracerebral infusion of contrast medium before vector application displayed substantial inhomogeneity of tissue staining indicating the need of test infusions to monitor the mechanical distribution of vectors. Visualization of therapeutic effects on tumor metabolism and documentation of gene expression using positron emission tomography indicated that molecular imaging technology appears to be essential for the further development of biological treatment strategies.     

Sexuelle Sucht?

The authors differentiates deviant (paraphilic) and non-deviant forms of a sexual addictive symptomatology. For the non-deviant forms, the diagnostic term paraphilia-related disorder is used. According to etiological factors, the authors discuss an interaction of a biological vulnerability, attachment and relationship problems, disorders of affect regulation as well as disinhibition of sexual excitation. Some individuals react to negative emotions, like depression or anxiety, with an increased sexual arousal. They may try to cope with negative emotions by being sexually active. However, the importance of the sexual stimulus itself should not be ignored. The authors describe specific psychotherapy, the attendance of self-help groups, and pharmacological treatment, especially with selective serotonin reuptake inhibitors.     

Microglia promote colonization of brain tissue by breast cancer cells in a Wnt‐dependent way

Although there is increasing evidence that blood‐derived macrophages support tumor progression, it is still unclear whether specialized resident macrophages, such as brain microglia, also play a prominent role in metastasis formation. Here, we show that microglia enhance invasion and colonization of brain tissue by breast cancer cells, serving both as active transporters and guiding rails. This is antagonized by inactivation of microglia as well as by the Wnt inhibitor Dickkopf‐2. Proinvasive microglia demonstrate altered morphology, but neither upregulation of M2‐like cytokines nor differential gene expression. Bacterial lipopolysacharide shifts tumor‐educated microglia into a classical M1 phenotype, reduces their proinvasive function, and unmasks inflammatory and Wnt signaling as the most strongly regulated pathways. Histological findings in human brain metastases underline the significance of these results. In conclusion, microglia are critical for the successful colonization of the brain by epithelial cancer cells, suggesting inhibition of proinvasive microglia as a promising antimetastatic strategy. © 2010 Wiley‐Liss, Inc.     

Protein kinase A regulates caspase-1 via Ets-1 in bone stromal cell-derived lesions: a link between cyclic AMP and pro-inflammatory pathways in osteoblast progenitors

Patients with genetic defects of the cyclic (c) adenosine-monophosphate (AMP)-signaling pathway and those with neonatal-onset multisystem inflammatory disease (NOMID) develop tumor-like lesions of the long bones. The molecular basis of this similarity is unknown. NOMID is caused by inappropriate caspase-1 activity, which in turn activates the inflammasome. The present study demonstrates that NOMID bone lesions are derived from the same osteoblast progenitor cells that form fibroblastoid tumors in mice and humans with defects that lead to increased cAMP-dependent protein kinase A (PKA) signaling. NOMID tumor cells showed high PKA activity, and an increase in their cAMP signaling led to PKA-specific activation of caspase-1. Increased PKA led to inflammation-independent activation of caspase-1 via over-expression of the proto-oncogene (and early osteoblast factor) Ets-1. In NOMID tumor cells, as in cells with defective PKA regulation, increased prostaglandin E2 (PGE2) led to increased cAMP levels and activation of Wnt signaling, like in other states of inappropriate PKA activity. Caspase-1 and PGE2 inhibition led to a decrease in cell proliferation of both NOMID and cells with abnormal PKA. These data reveal a previously unsuspected link between abnormal cAMP signaling and defective regulation of the inflammasome and suggest that caspase-1 and PGE2 inhibition may be therapeutic targets in bone lesions associated with defects of these two pathways.