Michael Müntener

The Role of 11C-Choline and 18F-Fluorocholine Positron Emission Tomography (PET) and PET/CT in Prostate Cancer: A Systematic Review and Meta-analysis

CONTEXT The role of positron emission tomography (PET) and PET/computed tomography (PET/CT) in prostate cancer (PCa) imaging is still debated, although guidelines for their use have emerged over the last few years. OBJECTIVE To systematically review and conduct a meta-analysis of the available evidence of PET and PET/CT using 11C-choline and 18F-fluorocholine as tracers in imaging PCa patients in staging and restaging settings. EVIDENCE ACQUISITION PubMed, Embase, and Web of Science (by citation of reference) were searched. Reference lists of review articles and included articles were checked to complement electronic searches. EVIDENCE SYNTHESIS In staging patients with proven but untreated PCa, the results of the meta-analysis on a per-patient basis (10 studies, n = 637) showed pooled sensitivity, specificity, and diagnostic odds ratio (DOR) of 84% (95% confidence interval [CI], 68-93%), 79% (95% CI, 53-93%), and 20.4 (95% CI, 9.9-42.0), respectively. The positive and negative likelihood ratios were 4.02 (95% CI, 1.73-9.31) and 0.20 (95% CI, 0.11-0.37), respectively. On a per-lesion basis (11 studies, n = 5117), these values were 66% (95% CI, 56-75%), 92% (95% CI, 78-97%), and 22.7 (95% CI, 8.9-58.0), respectively, for pooled sensitivity, specificity, and DOR; and 8.29 (95% CI, 3.05-22.54) and 0.36 (95% CI, 0.29-0.46), respectively, for positive and negative likelihood ratios. In restaging patients with biochemical failure after local treatment with curative intent, the meta-analysis results on a per-patient basis (12 studies, n = 1055) showed pooled sensitivity, specificity, and DOR of 85% (95% CI, 79-89%), 88% (95% CI, 73-95%), and 41.4 (95% CI, 19.7-86.8), respectively; the positive and negative likelihood ratios were 7.06 (95% CI, 3.06-16.27) and 0.17 (95% CI, 0.13-0.22), respectively. CONCLUSIONS PET and PET/CT imaging with 11C-choline and 18F-fluorocholine in restaging of patients with biochemical failure after local treatment for PCa might help guide further treatment decisions. In staging of patients with proven but untreated, high-risk PCa, there is limited but promising evidence warranting further studies. However, the current evidence shows crucial limitations in terms of its applicability in common clinical scenarios.

FOXA1 Promotes Tumor Progression in Prostate Cancer and Represents a Novel Hallmark of Castration-Resistant Prostate Cancer

Forkhead box protein A1 (FOXA1) modulates the transactivation of steroid hormone receptors and thus may influence tumor growth and hormone responsiveness in prostate cancer. We therefore investigated the correlation of FOXA1 expression with clinical parameters, prostate-specific antigen (PSA) relapse-free survival, and hormone receptor expression in a large cohort of prostate cancer patients at different disease stages. FOXA1 expression did not differ significantly between benign glands from the peripheral zone and primary peripheral zone prostate carcinomas. However, FOXA1 was overexpressed in metastases and particularly in castration-resistant cases, but was expressed at lower levels in both normal and neoplastic transitional zone tissues. FOXA1 levels correlated with higher pT stages and Gleason scores, as well as with androgen (AR) and estrogen receptor expression. Moreover, FOXA1 overexpression was associated with faster biochemical disease progression, which was pronounced in patients with low AR levels. Finally, siRNA-based knockdown of FOXA1 induced decreased cell proliferation and migration. Moreover, in vitro tumorigenicity was inducible by ARs only in the presence of FOXA1, substantiating a functional cooperation between FOXA1 and AR. In conclusion, FOXA1 expression is associated with tumor progression, dedifferentiation of prostate cancer cells, and poorer prognosis, as well as with cellular proliferation and migration and with AR signaling. These findings suggest FOXA1 overexpression as a novel mechanism inducing castration resistance in prostate cancer.

Robotic-Assisted Laparoscopic Extended Pelvic Lymph Node Dissection for Prostate Cancer: Surgical Technique and Experience with the First 99 Cases

BACKGROUND To date, there is still a paucity of data in the literature on robotic-assisted laparoscopic extended pelvic lymph node dissection (RALEPLND) in patients with prostate cancer. OBJECTIVE To assess the technical feasibility of RALEPLND and to present our surgical technique. DESIGN, SETTING, AND PARTICIPANTS From April 2006 to March 2008, we performed RALEPLND in 99 patients prior to robotic-assisted laparoscopic radical prostatectomy. Indications for RALEPLND were a prostate-specific antigen (PSA) > or = 10 ng/ml or a preoperative Gleason score > or = 7. The data were evaluated retrospectively. SURGICAL PROCEDURE The transperitoneal approach was used in all cases. In order to gain optimal access to the common iliac bifurcation, the five trocars were placed in a more cephalad position than in patients undergoing radical prostatectomy without RALEPLND. After identification of important landmarks, the lymphatics covering the external iliac vein, the obturator lymphatic packet, and the lymphatics overlying the internal iliac artery were removed on both sides. MEASUREMENTS The total lymph node yield, the frequency of lymph node metastases, and the complication rate. RESULTS AND LIMITATIONS The median patient age was 64 yr (range: 45-78). The median preoperative PSA level was 7.7 ng/ml (range: 1.5-84.6). The median number of lymph nodes harvested was 19 (range: 8-53). In 16 patients (16%), we found lymph node metastasis. Complications occurred in seven patients (7%). CONCLUSIONS RALEPLND is feasible, and its lymph node yield is well in the range of open series. The robotic-assisted laparoscopic approach in itself does not seem to limit a surgeons ability to perform a complete extended pelvic lymph node dissection.

Profiling Gastrin-Releasing Peptide Receptor in Prostate Tissues: Clinical Implications and Molecular Correlates

The gastrin‐releasing peptide receptor (GRPR) has emerged as an attractive target for both therapeutic and diagnostic appliances, but has only insufficiently been characterized in the human prostate so far. The aim of this study is to profile GRPR in a large cohort and correlate it with clinicopathologic and molecular parameters.

Intraoperative complications of laparoscopic adrenalectomy

A laparoscopic or retroperitoneoscopic access to the adrenal gland is the standard of care for adrenalectomy in most cases. Although in laparoscopic adrenalectomy the approach is minimally invasive, the procedure is challenging. This is reflected in the scope of possible complications. The surgeon must consider complications related to the anatomical topography of the adrenal gland, which typically encompasses the complications known from open surgery and complications related to the minimal invasive access. In this topic paper we will address the most frequently encountered complications of adrenalectomy: vascular injuries, injuries of the bowel, pleural tears, and injuries to the liver, spleen and pancreas. Fortunately, these complications occur rarely. However, many of these complications can have devastating consequences. Therefore, it’s the surgeon’s obligation to be aware of the possible complications he might encounter during laparoscopic adrenalectomy. This awareness is essential for their prevention and it helps the laparoscopic surgeon to identify complications intraoperatively.

Daily Pomegranate Intake Has No Impact on PSA Levels in Patients with Advanced Prostate Cancer - Results of a Phase IIb Randomized Controlled Trial.

Pomegranate has been shown to prolong PSA doubling time in early prostate cancer, but no data from a placebo controlled trial has been published yet. The objective of this study was to prospectively evaluate the impact of pomegranate juice in patients with prostate cancer. We conducted a phase IIb, double blinded, randomized placebo controlled trial in patients with histologically confirmed prostate cancer. Only patients with a PSA value ≥ 5ng/ml were included. The subjects consumed 500 ml of pomegranate juice or 500 ml of placebo beverage every day for a 4 week period. Thereafter, all patients received 250 ml of the pomegranate juice daily for another 4 weeks. PSA values were taken at baseline, day 14, 28 and on day 56. The primary endpoint was the detection of a significant difference in PSA serum levels between the groups after one month of treatment. Pain scores and adherence to intervention were recorded using patient diaries. 102 patients were enrolled. The majority of patients had castration resistant prostate cancer (68%). 98 received either pomegranate juice or placebo between October 2008 and May 2011. Adherence to protocol was good, with 94 patients (96%) completing the first period and 87 patients (89%) completing both periods. No grade 3 or higher toxicities occurred within the study. No differences were detected between the two groups with regard to PSA kinetics and pain scores. Consumption of pomegranate juice as an adjunct intervention in men with advanced prostate cancer does not result in significant PSA declines compared to placebo.

Insulin-like growth factor II mRNA binding protein 3 (IMP3) is overexpressed in prostate cancer and correlates with higher Gleason scores

BackgroundThe oncofetal protein insulin-like growth factor II mRNA binding protein 3 (IMP3) is an important factor for cell-migration and adhesion in malignancies. Recent studies have shown a remarkable overexpression of IMP3 in different human malignant neoplasms and also revealed it as an important prognostic marker in some tumor entities. To our knowledge, IMP3 expression has not been investigated in prostate carcinomas so far.MethodsImmunohistochemical stainings for IMP3 were performed on tissue microarray (TMA) organized samples from 507 patients: 31 normal prostate tissues, 425 primary carcinomas and 51 prostate cancer metastases or castration-resistant prostate cancers (CRPC). IMP3 immunoreactivity was semiquantitatively scored and correlated with clinical-pathologic parameters including survival.ResultsIMP3 is significantly stronger expressed in prostate carcinomas compared to normal prostate tissues (p < 0.0001), but did not show significant correlation with the pT-stage, the proliferation index (MIB1), preoperative serum PSA level and the margin status. Only a weak and slightly significant correlation was found with the Gleason score and IMP3 expression failed to show prognostic significance in clinico-pathological correlation-analyses.ConclusionsAlthough IMP3 is overexpressed in a significant proportion of prostate cancer cases, which might be of importance for novel therapeutic approaches, it does not appear to possess any immediate diagnostic or prognostic value, limiting its potential as a tissue biomarker for prostate cancer. These results might be corroborated by the fact, that two independent tumor cohorts were separately reviewed.

Lithium Triborate Laser Vaporization of the Prostate Using the 120 W, High Performance System Laser: High Performance All the Way?

PURPOSE Technical modifications of the 120 W lithium-triborate laser have been implemented to increase power output, and prevent laser fiber degradation and loss of power output during laser vaporization of the prostate. However, visible alterations at the fiber tip and the subjective impression of decreasing ablative effectiveness during lithium-triborate laser vaporization indicate that delivering constantly high laser power remains a relevant problem. Thus, we evaluated the extent of laser fiber degradation and loss of power output during 120 W lithium-triborate laser vaporization of the prostate. MATERIALS AND METHODS We investigated 46 laser fibers during routine 120 W lithium-triborate laser vaporization in 35 patients with prostatic bladder outflow obstruction. Laser beam power was measured at baseline and after the application of each 25 kJ during laser vaporization. Fiber tips were microscopically examined after the procedure. RESULTS Mild to moderate degradation at the emission window occurred in all fibers, associated with a loss of power output. A steep decrease to a median power output of 57.3% of baseline was detected after applying the first 25 kJ. Median power output at the end of the defined 275 kJ lifespan of the fibers was 48.8%. CONCLUSIONS Despite technical refinements of the 120 W lithium-triborate laser fiber degradation and significantly decreased power output are still detectable during the procedure. Laser fibers are not fully appropriate for the high power delivery of the new system. There is still potential for further improvement in the laser performance.

Peri-operative morbidity and changes in symptom scores after transurethral prostatectomy in Switzerland: results of an independent assessment of outcome

To assess, in a prospective study, the contemporary outcome of transurethral resection of the prostate (TURP) in patients with benign prostatic hyperplasia (BPH) in Switzerland, by evaluating peri‐operative morbidity and changes in lower urinary tract symptoms (LUTS).

Multidrug resistance protein 4 (MRP4) expression in prostate cancer is associated with androgen signaling and decreases with tumor progression

Multidrug resistance protein 4 (MRP4) is a transmembrane transport protein found in many cell types and is involved in substrate-specific transport of endogenous and exogenous substrates. Recently, it has shown to be expressed in prostate cancer cell lines and to be among the most commonly upregulated transcripts in prostate cancer, although a comprehensive expression analysis is lacking so far. We aimed to investigate its expression by immunohistochemistry in a larger cohort of neoplastic and nonneoplastic prostate tissues (n = 441) and to correlate its expression with clinicopathological parameters including PSA-free survival times and molecular correlates of androgen signaling (androgen receptor (AR), prostate-specific antigen (PSA), and forkhead box A (FoxA)). MRP4 is widely expressed in benign and neoplastic prostate epithelia, but its expression gradually decreases during tumor progression towards castrate-resistant disease. Concordantly, it correlated with conventional prognosticators of disease progression and—within the group of androgen-dependent tumors—with AR and FoxA expression. Moreover, lower levels of MRP4 expression were associated with shorter PSA relapse-free survival times in the androgen-dependent group. In benign tissues, we found zone-dependent differences of MRP4 expression, with the highest levels in the peripheral and central zones. Although MRP4 is known to be regulated in prostate cancer, this study is the first to demonstrate a gradual downregulation of MRP4 protein during malignant tumor progression and a prognostic value of this loss of expression.