Purpose We studied whether immunohistochemical expression of p53 in Wilms tumors correlates with tumor aggressiveness. We also examined whether preoperative chemotherapy results in any alteration of ...p53 expression. Materials and Methods A total of 18 patients underwent preoperative chemotherapy and 30 underwent immediate surgery for Wilms tumor. All children were younger than 10 years and had histologically confirmed disease. Patients with a bilateral tumor or a syndrome related to Wilms tumor were excluded. All pathology slides were uniformly stained for p53 protein, and p53 staining density and intensity were scored. The p53 scoring was then compared to the clinical behavior of the Wilms tumor, ie unfavorable tumor staging, and survival and recurrence rates. Results In the direct surgery and the preoperatively treated groups p53 positivity correlated with unfavorable Wilms tumor staging (p = 0.007). In addition, a positive p53 correlation predicted poorer survival (p = 0.017). Interestingly patients who underwent preoperative chemotherapy had an increased intensity of p53 staining compared to the direct surgery group (p <0.001). Conclusions This study provides preliminary evidence that a higher score for immunohistochemical p53 expression correlates with unfavorable Wilms tumor staging and predicts poorer survival. This test could become a useful addition to the current histopathological analysis of Wilms tumor.
Abstract Purpose Accurate staging modalities to diagnose lymph node involvement in patients with prostate cancer (PCa) are lacking. We wanted to prospectively assess sensitivity, specificity, and ...positive predictive value (PPV) and negative predictive value of11 C-choline positron emission tomography (PET)-computed tomography (CT) and diffusion-weighted (DW) magnetic resonance imaging (MRI) for nodal staging in patients with PCa at high risk for lymph node involvement. Material and methods In total, 75 patients with a risk≥10% but<35% for lymph node (LN) metastases (Partin tables) who had N0 lesions based on the findings of contrast-enhanced CT scans were included. Patients underwent11 C-choline PET-CT and DW MRI before surgery, which consisted of a superextended lymph node dissection followed by radical prostatectomy. LNs were serially sectioned and histopathologically examined after pankeratin staining. These results were used as the gold standard to compare with the imaging results. Results Of 1,665 resected LNs (median = 21, range: 7–49), 106 affected LNs (median = 2, range: 1–10) were found in 37 of 75 patients (49%). On a region-based analysis, we found a low sensitivity of 8.2% and 9.5% and a PPV of 50.0% and 40.0% for11 C-choline PET-CT and DW MRI, respectively. The patient-based analysis showed a sensitivity of 18.9% and 36.1% for and a PPV of 63.6% and 86.7%11 C-choline PET-CT and DW MRI, respectively. Even when both imaging modalities were combined, sensitivity values remained too low to be clinically useful. Conclusions Because of the low sensitivity, there is no indication for routine clinical use of either11 C-choline PET-CT or DW MRI for LN staging in patients with PCa, in whom CT scan findings were normal.
Abstract Context The gained expertise in the surgical technique of partial nephrectomy (PN) with excellent oncologic outcome and reduced morbidity has contributed to more frequent use of PN in many ...centres of reference, and the recent evidence favouring PN over radical nephrectomy (RN) in the prevention of chronic kidney disease and possibly linking it to a better overall survival (OS) will constitute a strong argument for wider use of PN. Objective To objectively analyse the advantages of PN over RN and to evaluate the risk–benefit ratio of expanding the indications of PN T1b renal cortical tumours. Evidence acquisition Literature searches on English-language publications were performed using the National Library of Medicine database. The queries included the keywords partial nephrectomy and nephron sparing surgery. Eight hundred four references were scrutinised, and 175 publications were identified and reviewed. Sixty-nine articles were selected for this review. These references formed the basis for this analysis and were selected based on their relevance and the importance of their content. Evidence synthesis The use of PN has been steadily increasing, particularly in tertiary care centres. This trend is now strengthened by evidence supporting the role of PN in reducing the risk of chronic kidney disease in patients with renal masses ≤4 cm. A wider use of PN for larger tumours, granted technical feasibility, is supported by the preliminary evidence, suggesting an OS advantage favouring PN over RN. However, the potential for selection bias and residual confounding factors may contribute to the observed difference. In the carefully selected patients with tumours >4 cm, PN obtained equivalent oncologic outcome to that achieved after RN. Although higher morbidity rates were seen after PN, the complication type and severity were not prohibitive. Conclusions The available evidence supports elective PN as the standard surgical treatment for renal cortical tumours ≤4 cm. For larger tumours, PN has demonstrated feasibility and oncologic safety in the carefully selected patient population studied.
Abstract Objective In patients with a long life expectancy with high-risk (HR) prostate cancer (PCa), the chance to die from PCa is not negligible and may change significantly according to the time ...elapsed from surgery. The aim of this study was to evaluate long-term survival patterns in young patients treated with radical prostatectomy (RP) for HRPCa. Materials and methods Within a multiinstitutional cohort, 600 young patients (≤59 years) treated with RP between 1987 and 2012 for HRPCa (defined as at least one of the following adverse characteristics: prostate specific antigen>20, cT3 or higher, biopsy Gleason sum 8–10) were identified. Smoothed cumulative incidence plot was performed to assess cancer-specific mortality (CSM) and other cause mortality (OCM) rates at 10, 15, and 20 years after RP. The same analyses were performed to assess the 5-year probability of CSM and OCM in patients who survived 5, 10, and 15 years after RP. A multivariable competing risk regression model was fitted to identify predictors of CSM and OCM. Results The 10-, 15- and 20-year CSM and OCM rates were 11.6% and 5.5% vs. 15.5% and 13.5% vs. 18.4% and 19.3%, respectively. The 5-year probability of CSM and OCM rates among patients who survived at 5, 10, and 15 years after RP, were 6.4% and 2.7% vs. 4.6% and 9.6% vs. 4.2% and 8.2%, respectively. Year of surgery, pathological stage and Gleason score, surgical margin status and lymph node invasion were the major determinants of CSM (all P ≤0.03). Conversely, none of the covariates was significantly associated with OCM (all P ≥ 0.09). Conclusions Very long-term cancer control in young high-risk patients after RP is highly satisfactory. The probability of dying from PCa in young patients is the leading cause of death during the first 10 years of survivorship after RP. Thereafter, mortality not related to PCa became the main cause of death. Consequently, surgery should be consider among young patients with high-risk disease and strict PCa follow-up should enforce during the first 10 years of survivorship after RP.
Abstract Objectives This study compared the complications and the cancer control of elective nephron-sparing surgery (NSS) and radical nephrectomy (RN) in patients with a small (≤5 cm), solitary, ...low-stage N0 M0 tumour suspicious for renal cell carcinoma (RCC) and a normal contralateral kidney. Methods 541 patients were randomised in a prospective, multicentre, phase 3 trial to undergo NSS ( n = 268) or RN ( n = 273) together with a limited lymph node dissection. Results This publication reports only on the complications reported for both surgical methods. The rate of perioperative blood loss <0.5 l was slightly higher after RN (96.0% vs. 87.2%) and the rate of severe haemorrhage was slightly higher after NSS (3.1% vs. 1.2%). Ten patients (4.4%), all of whom were treated with NSS, developed urinary fistulas. Pleural damage (11.5% for NSS vs. 9.3% for RN) and spleen damage (0.4% for NSS and 0.4% for RN) were observed with similar rates in both groups. Postoperative computed tomography scanning abnormalities were seen in 5.8% of NSS and 2.0% of RN patients. Reoperation for complications was necessary in 4.4% of NSS and 2.4% of RN patients. Conclusions NSS for small, easily resectable, incidentally discovered RCC in the presence of a normal contralateral kidney can be performed safely with slightly higher complication rates than after RN. The oncologic results are eagerly awaited to confirm that NSS is an acceptable approach for small asymptomatic RCC.
Prostate cancer is the most prevalent cancer in men and predominantly affects older men (aged ≥70 years). The median age at diagnosis is 68 years; overall, two‐thirds of prostate cancer‐related ...deaths occur in men aged ≥75 years. With the exponential ageing of the population and the increasing life‐expectancy in developed countries, the burden of prostate cancer is expected to increase dramatically in the future. To date, no specific guidelines on the management of prostate cancer in older men have been published. The International Society of Geriatric Oncology (SIOG) conducted a systematic bibliographic search based on screening, diagnostic procedures and treatment options for localized and advanced prostate cancer, to develop a proposal for recommendations that should provide the highest standard of care for older men with prostate cancer. The consensus of the SIOG Prostate Cancer Task Force is that older men with prostate cancer should be managed according to their individual health status, which is mainly driven by the severity of associated comorbid conditions, and not according to chronological age. Existing international recommendations (European Association of Urology, National Comprehensive Cancer Network, and American Urological Association) are the backbone for localized and advanced prostate cancer treatment, but need to be adapted to patient health status. Based on a rapid and simple evaluation, patients can be classified into four different groups: 1, ‘Healthy’ patients (controlled comorbidity, fully independent in daily living activities, no malnutrition) should receive the same treatment as younger patients; 2, ‘Vulnerable’ patients (reversible impairment) should receive standard treatment after medical intervention; 3, ‘Frail’ patients (irreversible impairment) should receive adapted treatment; 4, Patients who are ‘too sick’ with ‘terminal illness’ should receive only symptomatic palliative treatment.
Objective
To compare functional outcomes, i.e. urinary incontinence (UI), voiding symptoms and quality of life, after open (ORP) and robot‐assisted radical prostatectomy (RARP).
Patients and Methods
...Between September 2009 and July 2011, 180 consecutive patients underwent radical prostatectomy; of these, 116 underwent ORP and 64 underwent RARP. We prospectively assessed the functional outcomes of each group during the first year of follow‐up.
We measured UI on the 3 days before surgery (24‐h pad test) and daily after surgery until total continence, defined as 3 consecutive days of 0 g urine leak, was achieved. Additionally, all patients were assessed before surgery and at 1, 3, 6 and 12 months after surgery using the International Prostate Symptom Score (IPSS) and the King's Health Questionnaire (KHQ).
All patients received pelvic floor muscle training until continence was achieved.
Kaplan–Meier analyses and Cox regression with correction for covariates were used to compare time to continence. A Mann–Whitney U‐test was used to assess IPSS and KHQ.
Results
Patients in the RARP group had a significantly lower D'Amico risk group allocation and underwent more nerve‐sparing surgery. Other characteristics were similar. Patients in the RARP group regained continence sooner than those in the ORP group (P = 0.007). In the RARP group, the median time to continence (16 vs 46 days, P = 0.026) was significantly shorter and the median amount of first day UI (44 vs 186 g, P < 0.01) was significantly smaller than in the ORP group. After correction for all covariates, the difference remained significant (P = 0.036, hazard ratio HR 1.522 (1.027–2.255). In addition, younger men, men with positive surgical margins and men without preoperative incontinence achieved continence sooner.
A comparison of time to continence between groups with a sufficient number of patients (intermediate risk and/or bilateral nerve‐sparing) still showed a faster return of continence after RARP, but the effect decreased in size and was nonsignificant (HR>1.2, P > 0.05).
Only six patients (two in the RARP and four in the ORP group) still had UI after 1 year.
Patients in the RARP group had significantly better IPSS scores at 1 (P = 0.013) and 3 (P = 0.038) months, and scored better in almost all KHQ aspects.
Conclusion
In this prospective trial, patients treated with RARP tended to regain urinary continence sooner than patients treated with ORP, but in subgroup analyses statistical significance disappeared and effect size decreased dramatically, indicating that the results must be interpreted with caution.
MicroRNAs (miRNAs), non-coding RNAs regulating gene expression, are frequently aberrantly expressed in human cancers. Next-generation deep sequencing technology enables genome-wide expression ...profiling of known miRNAs and discovery of novel miRNAs at unprecedented quantitative and qualitative accuracy. Deep sequencing was performed on 11 fresh frozen clear cell renal cell carcinoma (ccRCC) and adjacent non-tumoral renal cortex (NRC) pairs, 11 additional frozen ccRCC tissues, and 2 ccRCC cell lines (n = 35). The 22 ccRCCs patients belonged to 3 prognostic sub-groups, i.e. those without disease recurrence, with recurrence and with metastatic disease at diagnosis. Thirty-two consecutive samples (16 ccRCC/NRC pairs) were used for stem-loop PCR validation. Novel miRNAs were predicted using 2 distinct bioinformatic pipelines. In total, 463 known miRNAs (expression frequency 1-150,000/million) were identified. We found that 100 miRNA were significantly differentially expressed between ccRCC and NRC. Differential expression of 5 miRNAs was confirmed by stem-loop PCR in the 32 ccRCC/NRC samples. With respect to RCC subgroups, 5 miRNAs discriminated between non-recurrent versus recurrent and metastatic disease, whereas 12 uniquely distinguished non-recurrent versus metastatic disease. Blocking overexpressed miR-210 or miR-27a in cell line SKCR-7 by transfecting specific antagomirs did not result in significant changes in proliferation or apoptosis. Twenty-three previously unknown miRNAs were predicted in silico. Quantitative genome-wide miRNA profiling accurately separated ccRCC from (benign) NRC. Individual differentially expressed miRNAs may potentially serve as diagnostic or prognostic markers or future therapeutic targets in ccRCC. The biological relevance of candidate novel miRNAs is unknown at present.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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