Ulderico Parente

Neoadjuvant therapy with sorafenib in advanced renal cell carcinoma with vena cava extension submitted to radical nephrectomy.

A 71-year-old man with advanced left renal cell carcinoma (lymph node involvement and vena cava thrombus) was submitted to 6 months of neoadjuvant treatment with sorafenib before open radical nephrectomy. After sorafenib treatment and before surgery a new CT scan confirmed the presence of a 9.0 cm in diameter solid mass in the left kidney but a reduction in thrombus extension, limited to the left renal vein. At histological examination after radical nephrectomy, over 90% of the renal mass was substituted by necrotic tissue.

Magnetic resonance spectroscopic imaging (1H-MRSI) and dynamic contrast-enhanced magnetic resonance (DCE-MRI): pattern changes from inflammation to prostate cancer.

PURPOSE To assess (1)H-magnetic resonance spectroscopic imaging ((1)H-MRSI) and dynamic contrast-enhanced magnetic resonance (DCE-MRI) features in histologically confirmed prostatic chronic inflammation, prostatic intraepithelial neoplasia (PIN), low grade prostate cancer (LGPCa), and high grade prostate cancer (HGPCa). MATERIALS AND METHODS Ninety-six men were selected, who showed at histology a diagnosis of chronic inflammation (Group B), high grade (HG) PIN (Group C), or prostate cancer (LGPCa = Group D and HGPCa = Group E). RESULTS ANOVA analysis shows that inflammation (Group B) displays no significantly (p >.05) different choline and citrate levels when compared to HGPIN and LGPCa. CONCLUSION our results suggest the potential for these MR imaging techniques in the description of inflammatory and proliferative lesions inside the prostate gland.

The emerging role of targeted therapy in renal cell carcinoma (RCC): is it time for a neoadjuvant or an adjuvant approach?

PURPOSE We address whether rational and significant clinical data exist on using angiogenic targeted therapies as neoadjuvant or adjuvant options to nephrectomy in non-metastatic RCC. METHODS We reviewed the recent international literature by carrying out a PUBMED search. RESULTS Neoadjuvant: a possible indication for a neoadjuvant targeted therapy approach is to facilitate surgery, reducing risks for patients and increasing the possibility of removing the mass and improving oncological results. Adjuvant: three major phase III clinical trials are currently ongoing. The ASSURE trial (1 year on oral sunitinib, sorafenib or placebo), the SORCE trial (3 years on placebo versus 1 year on sorafenib, followed by 2 years on placebo versus 3 years on sorafenib), and the S-TRAC trial (1 year on sunitinib or placebo) analyze patients who are at high risk of relapse. CONCLUSIONS Rationale and needs for the neoadjuvant or adjuvant use of targeted therapies in RCC are relevant. Significant phase III trials on the adjuvant use of targeted therapy in RCC are ongoing.

Determination of the time for maximal response to neoadjuvant hormone therapy for prostate cancer using magnetic resonance with spectroscopy (MRSI) and dynamic contrast enhancement (DCEMR)

PURPOSE To determine the time-dependent metabolic and angiogenic changes that occur in prostate cancer (CaP) during neoadjuvant hormone therapy (HT), using a combination of MRSI and DCEMR analysis. MATERIALS AND METHODS This is a prospective study on a population of non-metastatic CaP submitted to neoadjuvant HT prior to radiation therapy. All cases homogeneously received a 6-month period of neoadjuvant HT using leuprorelin acetate 7.5 mg every 28 days. In all cases, a MRSI/DCEMR study was performed at baseline (pretreatment) and at regular intervals (4, 12, 24 weeks) during HT. Serum PSA was measured at baseline and at the same intervals (4, 12, 24 weeks). All MRI examinations were performed on a commercially available 3 T scanner. RESULTS There was a significant ( P < 0.01) time-dependent loss of all prostate metabolites during HT. In regions of CaP no significant variation in the absolute value of metabolites was reported at 1-month interval and a higher variation was observed at 24-week compared with 12-week interval. A complete metabolic atrophy was a common feature (30%) at a 24-week interval of HT, but not at short (4-week 0%), and lower at an intermediate interval (12-week 10%). At DCEMR, onset time and time to peak parameters significantly (P < 0.05) increased at 12- and 24-week intervals. CONCLUSIONS To individualize neoadjuvant HT courses prior to definitive treatment, the combination of MRSI and DCEMR may represent a valid noninvasive method, and the addition to PSA data could be used to better assess the time-dependent efficacy of HT in our patients.

Human papilloma virus DNA detection, p53 and Ki67 expression in penile verrucous and squamous cell carcinomas in the same patient.

I October 1998, a 44-year-old, heterosexual, married, Italian man, white race, referred to the Urology Clinic, “Sapienza” University of Rome, presented with a verrucous– surfaced nodule on the penis. He reported having noted the lesion for the first time 3 months before; the patient was not affected by other significant diseases. Physical examination showed a 2 cm, fungating, cauliflowerlike tumor with a large base located on the prepuce and coronal sulcus on the ventral side of the penis, without provoking pain. A local excision of the tumor was performed. The surgical specimen grossly measured 3.2 cm and appeared as an exophytic grey-white mass that involved the glans. Microscopically, it appeared as a differentiated papillary neoplasm with acanthosis and hypercheratosis, with variable length papillations and inconspicuous fibrovascular cores. The nuclei were round bland with slight atypias in the basal layer. Koilocytic changes were not evident. The tumor extended into the underlying stroma. The histologic diagnosis was verrucous carcinoma (Fig. 1A), stage I (pT1, N0, M0) according to TNM classification.1 We also established the proliferation index, as evaluated by Ki67 immunohistochemistry positivity, and the level of p53 reactivity.2 Immunohistochemical analysis of p53 and Ki67 demonstrated a low nuclear accumulation of mutated p53 and Ki67 proteins (20%). Physical examination and computed tomography were performed in each following year: no obvious masses were found in the inguinal or paraortic areas or in distant visceral organs, and no evidence of local recurrence was found. In October 2003, 5 years after the primary surgical treatment, the patient showed a 2 cm white ulcerated nodule within the scar of the primary operation. A second excision was performed and the specimens were taken for histologic and virological analysis. Grossly the nodule showed a 3 cm size superficially spreading with horizontal growth and superficial invasion. Microscopically the tumor presented moderate grade of differentiation, with predominant well differentiated keratinizing areas and some solid nonkeratinizing poorly differentiated areas. Small irregular nests or cords of atypical cells were present in lamina propria. The tumor was histologically diagnosed as squamous cell carcinoma (SCC) (Fig. 1B), stage II (pT2, NO, M0). Physical examination and computed tomography scan analysis were performed in the each following years, and no obvious masses were found in the inguinal or paraortic areas or in distant visceral organs. The p53 and Ki67 immunoreactivity showed high levels, 95% and 90%, respectively. A sample from the surgical specimens was taken for Human Papillomavirus (HPV) investigation. Total cellular DNA was purified from the sample and analysed for the presence of genomic DNA of any HPV type. Aliquots of the purified DNA were employed in PCR assays for checking the suitability of the sample (HLA gene) and amplifying a portion (450 bp) of HPV L1 gene with MY09-MY11 degenerated consensus primers3 (Fig. 1C). At the same time, samples were collected from the paraffin embedded block of the first tumor. DNA was extracted from small sections, using NucleoSpin Tissue kit (Machery Nagel), according to the manufacturer’s recommendations for paraffin-embedded tissue. Reduced DNA yield and fragmentation in fixed compared to fresh tissue were expected; MY09-MY11 primers did not allow detection of any HPV PCR products, so sample DNA was tested with the widely used general primers elongated at their 3 ends (GP5 /GP6 ).4 The shortness of the amplicon (150-bp fragment in L1) renders the amplification appropriate in DNA extracted from paraffin-embedded tissue, allowing the detection of a broad spectrum of mucosotropic HPV. Each PCR reaction was electrophoresed on agarose gel in parallel with positive (2 ng of plasmid containing the entire genome of different HPV genotypes) and negative (the complete reaction mix without DNA) controls (Fig. 1D), and PCR products of the proper length were purified and sequenced by automatic DNA sequencer (Applied Biosystem, mod.370A), according to Manufacturer’s specifications (Amplicycle Kit, Applied Biosystem). Sequence homology was determined by BLAST and Clustal W programs. In paraffin embedded sample of the first tumor, GP5 /GP6 primers amplified a fragment showing 99% identity to HPV18; whereas in the fresh biopsy from the second tumor, DNA of the probably high-risk (HR) HPV53 was found with MY09-MY11 primers. Moreover, in order to exclude the concomitant presence of other HPV, another PCR, amplifying E6/7 genes was performed on the HPV53 positive sample. In this PCR,5 a mixture of 4 couples of degenerated primers was employed to detect 36 different HPV genotypes amplifying fragments of various length (600–750 bp). The sequence analysis of the obtained amplicon confirmed the presence of HPV53 DNA (98% identity). From the *Departments of Urology, †Experimental Medicine, Section of Virology, “Sapienza” University of Rome, Rome, Italy; and ‡Section of Histopathology, “Sapienza” University of Rome, Rome, Italy. Supported by grant from Ministero dell’Università, Istruzione, Ricerca scientifica, MIUR-Italia. Correspondence: Anna Marta Degener, PhD, Department of Experimental Medicine, Section of Virology, “Sapienza” University, Viale di Porta Tiburtina, 28, 00185 Rome–ITALY. E-mail address: annamarta.degener@uniroma1.it. Received for publication August 12, 2008, and accepted February 4, 2009. DOI: 10.1097/OLQ.0b013e31819f6c2f Copyright

1971 COMPARATIVE EFFECT OF FINASTERIDE AND DUTASTERIDE ON CROMOGRANIN A LEVELS AS MARKER OF NEUROENDOCRINE DIFFERENTIATION IN PATIENTS WITH BENIGN PROSTATIC HYPERPLASIA

INTRODUCTION AND OBJECTIVES: To verify and to compare in benign prostatic hyperplasia (BPH) patients the effect of finasteride versus dutasteride therapy on chromogranin A (CgA) serum levels, as possible marker of neuroendocrine (NE) differentiation and activity into the prostate gland. METHODS: This is a prospective randomized study in which 60 consecutive men with clinical diagnosis of benign prostatic hyperplasia (BPH) were randomized to a 6-month period of finasteride 5 mg/day versus dutasteride 4 mg/day versus control (no therapy) strategy. Total prostate specific antigen (PSA), testosterone and CgA were analysed in all cases at randomization and therefore at 1, 3 and 6 month interval. RESULTS: In both Group A (finasteride) and Group B (dutasteride), but not in Group C (no therapy) a statistically significant increase (p 0.05) in serum CgA levels was found at 3-months and 6-month interval of therapy when compared with visit 0 .Comparing the three groups,either at 3-month or at 6-month interval, serum CgA was significantly (p 0.05) higher in Group A and Group B than in Group C. At each interval, no significant (p 0.05) difference between Group A and Group B was found. CONCLUSIONS: In our BPH population, 5 alpha reductase inhibitors, with no difference between finasteride and dutasteride, produce a significant increase in serum CgA levels probably related to NE activation into the prostate gland.

Anatomia chirurgica della prostata: cosa deve “vedere” l’imaging

L’evoluzione delle tecniche chirurgiche e l’affinamento delle metodiche di imaging hanno permesso, negli ultimi anni, di individuare nuovi aspetti anatomici di notevole importanza della prostata e delle strutture adiacenti. Tali scoperte hanno consentito nei pazienti sottoposti a intervento chirurgico per adenocarcinoma prostatico rilevanti miglioramenti per quanto concerne sia la sopravvivenza libera da malattia, sia la qualita della vita in termini di continenza urinaria e potenza sessuale. Tuttavia alcune strutture anatomiche non sono ancora state ben definite dal punto di vista topografico e funzionale. In questo capitolo sono analizzate le strutture che rivestono un ruolo principale nel trattamento chirurgico: prostata strutture di supporto fasci neurovascolari vascolarizzazione fasce pelviche sfintere uretrale drenaggio linfatico.

Benign Prostatic Hypertrophy: A Progressive Pathology. Hypothesis for a Preventive Therapy

The purpose of this review is to enhance prevention as a new key aspect in the treatment of BPH. The concept of BPH as a progressive disease helps to adopt new approaches to patient evaluation and treatment. The disease progression, with respect to the risk of bladder function complications and alterations, to the progression of symptoms, and to the deterioration of the quality of life, leads to new ways of treating patients through a preventive as well as a symptomatic approach, thanks also to the identification of some parameters associated with the risk of BPH progression, i. e. the prostate volume and the serum PSA. Furthermore, the concept of progression helps the clinician to identify different classes of BPH patients with different indications of medical treatment. The PLESS, ARIA and MTOPS multicentric studies point out the preventive potential of the therapy based on 5 alpha-reductase inhibitors (finasteride and dutasteride) or their combination with alpha-1 adrenergic blockers. Only a long term evaluation (4 years or more) can lead to the identification of statistically and clinically significant outcomes for the BPH preventive therapy.

Incidental Retrovesical “Proximal-Type” Epithelioid Sarcoma: Pitfall of Diagnosis

The article aims at presenting an uncommon case of retrovesically located “proximal-type” epithelioid sarcoma, incidentally found as a retrovesical mass during prostatectomy for benign prostatic hyperplasia. Clinical, pathological and immunohistochemical data are presented. More specifically, two transrectal ultrasounds (TRUS) revealed a prostate gland enhancement and no evidence of other pelvic masses. This case report underlines that the retrovesical location of this neoplasm may mislead from a correct clinical diagnosis.