Salvatore Siracusano

Validation of the 2009 TNM Version in a Large Multi-Institutional Cohort of Patients Treated for Renal Cell Carcinoma: Are Further Improvements Needed?

BACKGROUND A new edition of the TNM was recently released that includes modifications for the staging system of kidney cancers. Specifically, T2 cancers were subclassified into T2a and T2b (< or =10 cm vs >10 cm), tumors with renal vein involvement or perinephric fat involvement were classified as T3a cancers, and those with adrenal involvement were classified as T4 cancers. OBJECTIVE Our aim was to validate the recently released edition of the TNM staging system for primary tumor classification in kidney cancer. DESIGN, SETTING, AND PARTICIPANTS Our multicenter retrospective study consisted of 5339 patients treated in 16 academic Italian centers. INTERVENTION Patients underwent either radical or partial nephrectomy. MEASUREMENTS Univariable and multivariable Cox regression models addressed cancer-specific survival (CSS) after surgery. RESULTS AND LIMITATIONS In the study, 1897 patients (35.5%) were classified as pT1a, 1453 (27%) as pT1b, 437 (8%) as pT2a, 153 (3%) as pT2b, 1059 (20%) as pT3a, 117 (2%) as pT3b, 26 (0.5%) as pT3c, and 197 (4%) as pT4. At a median follow-up of 42 mo, 786 (15%) had died of disease. In univariable analysis, patients with pT2b and pT3a tumors had similar CSS, as did patients with pT3c and pT4 tumors. Moreover, both pT3a and pT3b stages included patients with heterogeneous outcomes. In multivariable analysis, the novel classification of the primary tumor was a powerful independent predictor of CSS (p for trend <0.0001). However, the substratification of pT1 tumors did not retain an independent predictive role. The major limitations of the study are retrospective design, lack of central pathologic review, and the small number of patients included in some substages. CONCLUSIONS The recently released seventh edition of the primary tumor staging system for kidney tumors is a powerful predictor of CSS. However, some of the substages identified by the classification have overlapping prognoses, and other substages include patients with heterogeneous outcomes. The few modifications included in this edition may have not resolved the most critical issues in the previous version.

Simple Enucleation is Equivalent to Traditional Partial Nephrectomy for Renal Cell Carcinoma: Results of a Nonrandomized, Retrospective, Comparative Study

PURPOSE The excision of the renal tumor with a substantial margin of healthy parenchyma is considered the gold standard technique for partial nephrectomy. However, simple enucleation showed excellent results in some retrospective series. We compared the oncologic outcomes after standard partial nephrectomy and simple enucleation. MATERIALS AND METHODS We retrospectively analyzed 982 patients who underwent standard partial nephrectomy and 537 who had simple enucleation for localized renal cell carcinoma at 16 academic centers between 1997 and 2007. Local recurrence, cancer specific survival and progression-free survival were the main outcomes of this study. The Kaplan-Meier method was used to calculate survival functions and differences were assessed with the log rank statistic. Univariable and multivariable Cox regression models addressed progression-free survival and cancer specific survival. RESULTS Median followup of the patients undergoing traditional partial nephrectomy and simple enucleation was 51 ± 37.8 and 54.4 ± 36 months, respectively (p = 0.08). The 5 and 10-year progression-free survival estimates were 88.9 and 82% after standard partial nephrectomy, and 91.4% and 90.8% after simple enucleation (p = 0.09). The 5 and 10-year cancer specific survival estimates were 93.9% and 91.6% after standard partial nephrectomy, and 94.3% and 93.2% after simple enucleation (p = 0.94). On multivariable analysis the adopted nephron sparing surgery technique was not an independent predictor of progression-free survival (HR 0.8, p = 0.55) and cancer specific survival (HR 0.7, p = 0.53) when adjusted for the effect of the other covariates. CONCLUSIONS To our knowledge this is the first multicenter, comparative study showing oncologic equivalence of standard partial nephrectomy and simple enucleation.

Lymphatic and vascular embolizations are independent predictive variables of inguinal lymph node involvement in patients with squamous cell carcinoma of the penis.

The objective of the current study was to identify independent clinical and pathologic variables that were predictive of lymph node involvement in patients with squamous cell carcinoma of the penis in a multicenter series with the intent to select patients who were suitable to undergo immediate inguinal lymphadenectomy.

Elective partial nephrectomy is equivalent to radical nephrectomy in patients with clinical T1 renal cell carcinoma: results of a retrospective, comparative, multi‐institutional study

Study Type – Therapy (cohort)

Postpartum urinary symptoms: prevalence and risk factors

OBJECTIVES To assess the prevalence of urinary symptoms, the relationship between urinary symptoms and vaginal descent, and the association between urinary symptoms and obstetric factors. STUDY DESIGN Five hundred and thirty-seven women were interviewed and underwent a urogynaecological evaluation 3 months after vaginal delivery. Quantitative-type variables were subjected to Students t test. Simple logistic regression analyses were carried out on the symptoms studied as a function of risk factors. RESULTS 8.2% of primiparae showed stress urinary incontinence and multiparae in 20% (P=0.0001); urge incontinence was present in 5.5% of primiparae and in 13% of multiparae (P=0.004). Significant correlations were found among operative vaginal delivery, dysuria (P=0.048) and frequency (P=0.036). Urinary incontinence appeared associated with induced labour with prostaglandins (P=0.018) and with general maternal factors, such as parity (P=0.001) and elevated weight at the beginning of pregnancy (P=0.019). CONCLUSIONS It is likely that the pathogenesis of postpartum urinary incontinence includes not only the effects of pelvic floor trauma on urethrovesical mobility under stress, but also a deficiency in urethral resistance caused by drugs, such as prostaglandins.

Effects of formalin, methacarn, and fineFIX fixatives on RNA preservation.

Formalin-fixed tissues represent the most abundant clinical material for retrospective studies. However, formalin highly affects macromolecules, impairing their extraction and analysis. In this study, the suitability of some potential substitutes of formalin for RNA-based applications has been considered. Conventional formalin was compared with methacarn and the commercial FineFIX. Their impact on overall RNA preservation was investigated in a cell line-based model fixed during a time course treatment and in a series of fixed human tissues. RNA yield was detected by Nanodrop; ribosomal RNA (rRNA) integrity by electrophoresis and the Agilent Bioanalyzer; messenger RNA (mRNA) integrity by Northern blot and endpoint reverse transcription-polymerase chain reaction; and mRNA amount by real-time polymerase chain reaction. In the cell line model, formalin fixation showed time-dependent detrimental effects on overall RNA preservation. Methacarn and FineFIX were more conservative on both rRNA and mRNA preservation and their impact was time-independent. In tissues, high rRNA degradation levels were found in all fixed specimens, contrasting with the results found in the cells. Conversely, the effects of the fixatives on mRNA integrity reflected the observations shown in the cell line model. In methacarn-fixed samples mRNA amount was also preserved, whereas in formalin and FineFIX-fixed samples it was notably lower when compared with the fresh frozen control. Alcohol-based fixatives are a good solution for long-term fixation of both cytologic and tissue samples by virtue of their time-independent effects on mRNA preservation. In fixed tissue samples, however, the potential effects of preanalytical tissue-related factors should be considered when performing mRNA quantitative analysis.

Dissecting the expression of EEF1A1/2 genes in human prostate cancer cells: the potential of EEF1A2 as a hallmark for prostate transformation and progression

Background:In prostate adenocarcinoma, the dissection of the expression behaviour of the eukaryotic elongation factors (eEF1A1/2) has not yet fully elucidated.Methods:The EEF1A1/A2 expressions were investigated by real-time PCR, western blotting (cytoplasmic and cytoskeletal/nuclear-enriched fractions) and immunofluorescence in the androgen-responsive LNCaP and the non-responsive DU-145 and PC-3 cells, displaying a low, moderate and high aggressive phenotype, respectively. Targeted experiments were also conducted in the androgen-responsive 22Rv1, a cell line marking the progression towards androgen-refractory tumour. The non-tumourigenic prostate PZHPV-7 cell line was the control.Results:Compared with PZHPV-7, cancer cells showed no major variations in EEF1A1 mRNA; eEF1A1 protein increased only in cytoskeletal/nuclear fraction. On the contrary, a significant rise of EEF1A2 mRNA and protein were found, with the highest levels detected in LNCaP. Eukaryotic elongation factor 1A2 immunostaining confirmed the western blotting results. Pilot evaluation in archive prostate tissues showed the presence of EEF1A2 mRNA in near all neoplastic and perineoplastic but not in normal samples or in benign adenoma; in contrast, EEF1A1 mRNA was everywhere detectable.Conclusion:Eukaryotic elongation factor 1A2 switch-on, observed in cultured tumour prostate cells and in human prostate tumour samples, may represent a feature of prostate cancer; in contrast, a minor involvement is assigned to EEF1A1. These observations suggest to consider EEF1A2 as a marker for prostate cell transformation and/or possibly as a hallmark of cancer progression.

Prevalence of urinary incontinence in young and middle-aged women in an Italian urban area

OBJECTIVE To investigate by questionnaire the prevalence and characteristics of urinary incontinence (UI) in a female population aged between 18 and 49. STUDY DESIGN Of 44,095 females aged 18-49.9 living in our urban area a sample of 10,000 subjects was sent a questionnaire and 3557 replied. The age-based analysis was performed on 2900 of these. RESULTS The overall prevalence of UI was 20%. 11% had suffered from nocturnal enuresis before 18 years old, 47% of parous women noted a relationship between the beginning of UI and delivery. Among the incontinent women 83% lost urine with physical exertion, and 44% had urge incontinence, 18% used diapers, 20% had consulted a physician and half of these had been referred for medical, surgical or rehabilitative therapy, 50% reported past or present urinary infections, 8% complained also of faecal incontinence, 22% considered loss of urine embarrassing and humiliating but only 6% revealed frustration and 2% were obliged to stay at home for long periods of time. Of the incontinents 62% defined themselves anxious or nervous and 22% of these ascribed an increase of urinary leakage to anxiety or to nervousness, 9% reported use of antidepressant drugs, 85% had sexual intercourse and only 2% considered UI as an impediment to a satisfying sexual activity. CONCLUSIONS UI is a common problem in young women. Urge incontinence seems to be prevalent in <30 aged women while stress incontinence occurs more frequently after this age.

Time to recurrence is a significant predictor of cancer‐specific survival after recurrence in patients with recurrent renal cell carcinoma – results from a comprehensive multi‐centre database (CORONA/SATURN‐Project)

To assess the prognostic impact of time to recurrence (TTR) on cancer‐specific survival (CSS) after recurrence in patients with renal cell carcinoma (RCC) undergoing radical nephrectomy or nephron‐sparing surgery. To analyse differences in clinical and histopathological criteria between patients with early and late recurrence.

Decreased nocturnal urinary antidiuretic hormone excretion in enuresis is increased by imipramine

Objective To assess the role of integrated nocturnal antidiuretic hormone (ADH) secretion in children with enuresis, and possible modifications induced by treatment with imipramine.