Nicolai Leonhartsberger

Vascular damage as a risk factor for benign prostatic hyperplasia and erectile dysfunction.

Associate Editor

Postchemotherapy Laparoscopic Retroperitoneal Lymph Node Dissection for Low-volume, Stage II, Nonseminomatous Germ Cell Tumor: First 100 Patients

BACKGROUND Retroperitoneal lymph node dissection (RPLND) is indicated after chemotherapy in case of radiologic incomplete remission or teratomatous elements in orchiectomy specimens. Open RPLND is associated with considerable morbidity, but technical difficulty of postchemotherapy laparoscopic RPLND (L-RPLND) can be significant; therefore, literature concerning pc L-RPLND is sparse. OBJECTIVE To evaluate feasibility and long-term oncologic outcome of postchemotherapy L-RPLND for clinical stage II disease at a single institution. DESIGN, SETTING, AND PARTICIPANTS Records of patients with nonseminomatous germ cell tumor who underwent postchemotherapy L-RPLND between 1993 and 2010 were retrospectively reviewed. Unilateral template resection was used until a bilateral nerve-sparing approach was introduced in 2004. Follow-up investigations were performed at 3-mo intervals for the first 3 yr, every 6 mo for the next 2 yr, and annually thereafter. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS This was a descriptive analysis. RESULTS AND LIMITATIONS The study cohort comprised 100 patients with stage II retroperitoneal disease (stage IIC: n=16; IIB: n=68; IIA with persisting tumor marker: n=16). Mean diameter of retroperitoneal masses before and after chemotherapy was 3.5 cm and 1.4 cm, respectively. Unilateral and bilateral templates were resected in 71 and 29 patients, respectively. Surgery was successfully completed in all but one patient, whose procedure was converted to open surgery due to bleeding. Mean operation time for unilateral and bilateral resection was 241 and 343 min, respectively. Mean blood loss was 84 ml. Postoperative complications were a large lymphocele in one patient and chylous ascites in another. Mean postoperative hospital stay was 3.9 d. L-RPLND specimens showed teratoma in 38 patients and active tumor in 2 patients. During a mean follow-up of 74 mo, one patient recurred. No recurrence was observed inside the applied surgical field. No patient died of tumor progression. After bilateral nerve-sparing postchemotherapy L-RPLND, 95.2% of patients reported antegrade ejaculation. CONCLUSIONS Postchemotherapy L-RPLND performed by experienced hands is feasible and associated with low morbidity and high oncologic efficacy.

Increased incidence of Leydig cell tumours of the testis in the era of improved imaging techniques

Study Type – Diagnostic (exploratory cohort)

Stress-related and homeostatic cytokines regulate Vγ9Vδ2 T-cell surveillance of mevalonate metabolism

The potentially oncogenic mevalonate pathway provides building blocks for protein prenylation and induces cell proliferation and as such is an important therapeutic target. Among mevalonate metabolites, only isopentenyl pyrophosphate (IPP) has been considered to be an immunologically relevant antigen for primate-specific, innate-like Vγ9Vδ2 T cells with antitumor potential. We show here that Vγ9Vδ2 T cells pretreated with the stress-related, inflammasome-dependent cytokine interleukin 18 (IL-18) were potently activated not only by IPP but also by all downstream isoprenoid pyrophosphates that exhibit combined features of antigens and cell-extrinsic metabolic cues. Vγ9Vδ2 T cells induced this way effectively proliferated even under severe lymphopenic conditions and the antioxidant N-acetylcysteine significantly improved reconstitution of γδ T cells predominantly with a central memory phenotype. The homeostatic cytokine IL-15 induced the differentiation of effector cells in an antigen-independent fashion, which rapidly produced abundant interferon γ (IFNγ) upon antigen re-encounter. IL-15 induced effector γδ T cells displayed increased levels of the cytotoxic lymphocyte-associated proteins CD56, CD96, CD161 and perforin. In response to stimulation with isoprenoid pyrophosphates, these effector cells upregulated surface expression of CD107a and exhibited strong cytotoxicity against tumor cells in vitro. Our data clarify understanding of innate immunosurveillance mechanisms and will facilitate the controlled generation of robust Vγ9Vδ2 T cell subsets for effective cancer immunotherapy.

In young adults with a low body mass index ultrasonography is sufficient as a diagnostic tool for ureteric stones.

Study Type – Diagnostic (case series) Level of Evidence 4

Organ‐sparing surgery does not lead to greater antisperm antibody levels than orchidectomy

To assess a possible development of antisperm antibodies (ASA), present in a high percentage of infertile patients, after organ‐sparing surgery for small testicular tumours, to identify any additional immunogenic effect of this procedure compared with standard orchidectomy.

C-reactive protein is a strong predictor for anaemia in renal cell carcinoma: role of IL-6 in overall survival.

Study Type – Prognostic (case series)

Routine scrotal ultrasonography during the follow‐up of patients with testicular cancer leads to earlier detection of asynchronous tumours and a high rate of organ preservation

Study Type – Diagnosis (case series)
Level of Evidence 4

Antigen-independent immune responses after dendritic cell vaccination

The ability of cultured, antigen-loaded dendritic cells (DCs) to induce antigen-specific T cell immunity in vivo has previously been demonstrated and confirmed. Immune monitoring naturally focuses on immunity against vaccine antigens and may thus ignore other effects of DC vaccination. Here we therefore focused on antigen-independent responses induced by DC vaccination of renal cell carcinoma patients.In addition to the anticipated response against the vaccine antigen KLH, vaccination with CD83+ monocyte-derived DCs resulted in a strong increase in the ex vivo proliferative and cytokine responses of PBMCs stimulated with LPS or BCG. In addition, LPS strongly enhanced the KLH-induced proliferative and cytokine response of PBMCs. Moreover, proliferative and cytokine responses of PBMCs stimulated with the homeostatic cytokines IL-7 and IL-15 were also clearly enhanced after DC vaccination. In contrast to LPS induced proliferation, which is well known to depend on monocytes, IL-7 induced proliferation was substantially enhanced after monocyte depletion indicating that monocytes limit IL-7 induced lymphocyte expansion.Our data indicate that DC vaccination leads to an increase in the ex vivo responsiveness of patient PBMCs consistent with a DC vaccination induced enhancement of T cell memory. Our findings also suggest that incorporation of bacterial components and homeostatic cytokines into immunotherapy protocols may be useful in order to enhance the efficacy of DC vaccination and that monocytes may limit DC vaccination induced immunity.

Orthotopic bladder replacement in women: Focus on functional results of a retrospective, single-centre study

Abstract Objective. The aim of this study was to investigate the functional and oncological outcomes of orthotopic neobladders in women with urothelial cancer. Material and methods. From 1993 to 2007, 61 women underwent radical cystectomy and orthotopic ileal neobladder using the hemi-Kock pouch or Skinner T pouch. Sixteen of them were excluded owing to a lack of available follow-up data. Finally, 39 women with diagnosed TCC were included in this retrospective study. Demographic data, functional outcome including micturition characteristics such as voided volume, continence situation, use of clean intermittent catheterization (CIC), residual urine volume and recurrence rate were collected 3, 6 and >12 months after surgery. Results. Tumours were non-muscle-invasive in 13 patients (pT1; 32.8%) with isolated carcinoma in situ (after failure of bacillus Calmette–Guérin) in five patients (13.0%) and muscle-invasive in 19 patients (pT2–3; 49.0%), extensive superficial bladder cancer was shown in one patient (2.6%), and remaining dysplasia after transurethral resection of the bladder for T1 G2 in one patient (2.6%). Median follow-up was 37 (range 3–165) months. Day-time (71.4%) and night-time (67.8%) continence (0–1 pad/24 h) 3 months postoperatively increased to 83.8% on long-term follow-up. Clean intermittent self-catheterization was required by 20%. At a mean follow-up of 39.5 (8–86) months, two women experienced local recurrence (septum rectovaginale, pelvic floor), urethral recurrence was seen in 5.2% and distant metastasis (pulmonary, peritoneal carcinosis) also in 5.2%. Conclusions. Orthotopic bladder replacement is an efficient option in appropriately selected women undergoing radical cystectomy, with encouraging functional outcome and low urethral recurrence rates, similar to published literature in men.