Long-term oncological and surgical outcomes after Video Endoscopic Inguinal Lymphadenectomy (VEIL) in patients with penile cancer.

OBJECTIVE: To report outcomes from the largest multicenter series of penile cancer patients undergoing video endoscopic inguinal lymphadenectomy (VEIL). MATERIALS AND METHODS: Retrospective multicenter analysis. Authors of 21 centers from the Penile Cancer Collaborative Coalition-Latin America (PeC-LA) were included. All centers performed the procedure following the same previously described standardized technique. Inclusion criteria included penile cancer patients with no palpable lymph nodes and intermediate/high-risk disease and those with non-fixed palpable lymph nodes less than 4 cm in diameter. Categorical variables are shown as percentages and frequencies whereas continuous variables as mean and range. RESULTS: From 2006 to 2020, 210 VEIL procedures were performed in 105 patients. Mean age was 58 (45-68) years old. Mean operative time was 90 minutes (60-120). Mean lymph node yield was 10 nodes (6-16). Complication rate was 15.7%, including severe complications in 1.9% of procedures. Lymphatic and skin complications were noted in 8.6 and 4.8% of patients, respectively. Histopathological analysis revealed lymph node involvement in 26.7% of patients with non-palpable nodes. Inguinal recurrence was observed in 2.8% of patients. 10y- overall survival was 74.2% and 10-y cancer specific survival was 84.8%. CSS for pN0, pN1, pN2 and pN3 were 100%, 82.4%, 72.7% and 9.1%, respectively. CONCLUSION: VEIL seems to offer appropriate long term oncological control with minimal morbidity. In the absence of non-invasive stratification measures such as dynamic sentinel node biopsy, VEIL emerged as the alternative for the management of non-bulky lymph nodes in penile cancer.

Independent external validation of nomogram to predict extracapsular extension in patients with prostate cancer.

INTRODUCTION: The objective of this study was to perform an independent external validation of the Giganti-Coppola nomogram (GCN), which uses clinical and radiological parameters to predict prostate extracapsular extension (ECE) on the final pathology of patients undergoing radical prostatectomy (RP). MATERIAL AND METHODS: Seventy-two patients diagnosed with prostate cancer (PCa), who were RP candidates from two institutions, were prospectively included. All patients underwent preoperative multi-parametric magnetic resonance imaging (mpMRI) at 1.5 T, without the use of an endorectal coil, with multiplanar images in T1WI, T2WI, DWI, and DCE. The AUC and a calibration graph were used to validate the nomogram, using the regression coefficients of the Giganti-Coppola study. RESULTS: The original nomogram had an AUC of 0.90 (p = 0.001), with a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 100%, 5.1%, 47.1%, 100%, and 48%, respectively. The calibration graph showed an overestimation of the nomogram for ECE. CONCLUSION: The GCN has an adequate ability in predicting ECE; however, in our sample, it showed limited accuracy and overestimated likelihood of ECE in the final pathology of patients with PCa submitted to RP. KEY POINTS: • Knowledge of preoperative local staging of prostate cancer is essential for surgical treatment. Extracapsular extension increases the chance of positive surgical margins. • Imaging modalities such as mpMRI alone does not have suitable accuracy in local staging. • Giganti-Coppola's nomogram achieved an adequate ability in predicting ECE.

Robotic partial nephrectomy shortens warm ischemia time, reducing suturing time kinetics even for an experienced laparoscopic surgeon: a comparative analysis.

OBJECTIVES: Laparoscopic and robotic partial nephrectomy (LPN and RPN) are strongly related to influence of tumor complexity and learning curve. We analyzed a consecutive experience between RPN and LPN to discern if warm ischemia time (WIT) is in fact improved while accounting for these two confounding variables and if so by which particular aspect of WIT. METHODS: This is a retrospective analysis of consecutive procedures performed by a single surgeon between 2002-2008 (LPN) and 2008-2012 (RPN). Specifically, individual steps, including tumor excision, suturing of intrarenal defect, and parenchyma, were recorded at the time of surgery. Multivariate and univariate analyzes were used to evaluate influence of learning curve, tumor complexity, and time kinetics of individual steps during WIT, to determine their influence in WIT. Additionally, we considered the effect of RPN on the learning curve. RESULTS: A total of 146 LPNs and 137 RPNs were included. Considering renal function, WIT, suturing time, renorrhaphy time were found statistically significant differences in favor of RPN (p < 0.05). In the univariate analysis, surgical procedure, learning curve, clinical tumor size, and RENAL nephrometry score were statistically significant predictors for WIT (p < 0.05). RPN decreased the WIT on average by approximately 7 min compared to LPN even when adjusting for learning curve, tumor complexity, and both together (p < 0.001). CONCLUSIONS: We found RPN was associated with a shorter WIT when controlling for influence of the learning curve and tumor complexity. The time required for tumor excision was not shortened but the time required for suturing steps was significantly shortened.

Association between family history of prostate cancer and positive biopsies in a Brazilian screening program.

PURPOSE: To test the association between family history of prostate cancer (FH) and prostate cancer (PCa) risk in a large screening program in Brazil, as no conclusive study has yet investigated this. METHODS: Between 2004 and 2007, 17,569 men were screened in 231 small municipalities using mobile screening units. Positive FH was defined as any relative having PCa among screened men. Men were biopsied if they had digital rectal examination suggestive of PCa or PSA >4.0 ng/mL or PSA of 2.5-4 ng/mL with percent free PSA ≤ 15 %. We analyzed the association between FH and PCa using multivariable logistic regression in the first screening round of the program. RESULTS: Positive FH was present in 735 men (4.2 % of total), and they were younger, better educated and more likely to have had previous PCa screening (41.5 vs. 28.5 %; P < 0.001) compared to men with negative FH. FH status did not affect compliance rates in men recommended to undergo biopsy (P = 0.94). In first round, PCa was detected in 3.1 % of screened men (n = 552). In multivariable analysis, positive FH was associated with increased PCa risk (OR = 1.79; 95 % CI, 1.21-2.65; P = 0.003). However, Gleason scores (P = 0.78) or percent of positive cores (P = 0.32) among men with positive biopsies were similar, regardless of FH status. CONCLUSIONS: In Brazil, men with positive FH were at increased PCa risk, which could not be explained by differential biopsy rates. This finding suggests that FH is also a true PCa risk factor in Brazil, a country with highly diverse population in terms of race, ethnicity, culture and socioeconomic status.

Association between literacy, compliance with prostate cancer screening, and cancer aggressiveness: results from a Brazilian screening study.

PURPOSE: Little is known about the effects of literacy levels on prostate cancer screening. This study evaluates the association between literacy, compliance with screening, and biopsy findings in a large Brazilian screening study. MATERIALS AND METHODS: We analyzed 17,571 men screened for PCa with digital rectal examination (DRE) and total and free prostate-specific antigen (PSA) from January 2004 to December 2007. Of those, 17,558 men had information regarding literate status. Full urological evaluation in a specialized cancer center was recommended in the case of: a) suspicious DRE, b) PSA > 4.0 ng/mL, or c) PSA 2.5-3.9 ng/mL and free/total PSA (f/tPSA) ratio 15%. Transrectal ultrasound guided prostate biopsy (14 cores) was performed upon confirmation of these findings after the patient's consent. Patients' compliance with screening recommendations and biopsy results were evaluated according to literacy levels. RESULTS: an abnormal PSA, a suspicious DRE, or both were present in 73.2%, 19.7%, and 7.1% of those men who underwent biopsy, respectively. PCa was diagnosed in 652 men (3.7%). Previous PSAs or DREs were less common among illiterate men (p < 0.0001). Additionally, illiterate men were less prone to attend to further evaluations due to an abnormal PSA or DRE (p < 0.0001). PSA levels > 10 mg/mL (p = 0.03), clinical stage > T2a (p = 0.005), and biopsy Gleason > 7 (p = 0.02) were more common among illiterate men. CONCLUSIONS: In a screened population, literacy levels were associated with prior PCa evaluations and with compliance with screening protocols. Illiterate men were at higher risk of being diagnosed with more advanced and aggressive PCa.

Implications of Regionalizing Care in the Developing World: Impact of Distance to Referral Center on Compliance to Biopsy Recommendations in a Brazilian Prostate Cancer Screening Cohort.

Given growing specialization in medical care, optimal care may require regionalization, which may create access barriers. We tested this within a large prostate cancer (PC) screening program in Brazil. In 2004-2007, Barretos Cancer Hospital prospectively screened men for PC throughout rural Brazil. Men with abnormal screen were referred for follow-up and possible biopsy. We tested the link between distance from screening site to Barretos Cancer Hospital and risk of noncompliance with showing up for biopsy, PC on biopsy and, among those with PC, PC grade using crude and multivariable logistic regression analysis. Among 10,467 men undergoing initial screen, median distance was 257 km (IQR: 135-718 km). On crude and multivariable analyses, farther distance was significantly linked with biopsy noncompliance (OR/100 km: 0.83, P < 0.001). Among men who lived within 150 km of Barretos Cancer Hospital, distance was unrelated to compliance (OR/100 km: 1.09, P=0.87). There was no association between distance and PC risk or PC grade (all P > 0.25). In Brazil, where distances to referral centers can be large, greater distance was related to reduced biopsy compliance in a PC screening cohort. Among men who lived within 150 km, distance was unrelated to compliance. Care regionalization may reduce access when distances are large.

Nuclear loss and cytoplasmic expression of androgen receptor in penile carcinomas: role as a driver event and as a prognosis factor.

Androgen receptor (AR) is a member of the steroid and nuclear family receptor that acts as transcription factor. AR signaling plays pivotal role in the development and progression of prostate cancer. However, the role of AR in penile cancer (PeCa) is poorly explored. Our previous molecular studies unveiled frequent AR mRNA loss in PeCa, which was further predicted as a major driver alteration in this neoplasm. Herein, we assessed the AR protein expression in 59 usual PeCa tissues and 42 surrounding normal tissues (SNT) by immunohistochemistry using a tissue microarray. In a paired analysis, we found a total absence of nuclear AR expression in PeCa while 95.2% of SNT samples presented strong nuclear AR expression (P < 0.001). Interestingly, 17 of 42 PeCa presented weak or moderate cytoplasmic AR staining, contrasting with 5 of 42 SNT (P = 0.008). Increased levels of AR cytoplasmic expression were related with poor prognosis features including advanced clinical staging (P = 0.044), compromised surgical margins (P = 0.005), and pathological inguinal node status (P = 0.047). Furthermore, AR cytoplasmic expression was also related with shorter overall survival (P = 0.032). In conclusion, the frequent loss of nuclear AR protein levels suggests a potential function in PeCa development. Based on this result, the androgen deprivation therapy is not indicated for PeCa patients. In addition, the AR cytoplasmic expression found in a significant number of cases (40.5%) showed prognostic value and pathways activated by the non-genomic AR signaling may represent a promising therapeutic strategy.

Long-term oncological and surgical outcomes after Video Endoscopic Inguinal Lymphadenectomy (VEIL) in patients with penile cancer

ABSTRACT Objective: To report outcomes from the largest multicenter series of penile cancer patients undergoing video endoscopic inguinal lymphadenectomy (VEIL). Materials and Methods: Retrospective multicenter analysis. Authors of 21 centers from the Penile Cancer Collaborative Coalition-Latin America (PeC-LA) were included. All centers performed the procedure following the same previously described standardized technique. Inclusion criteria included penile cancer patients with no palpable lymph nodes and intermediate/high-risk disease and those with non-fixed palpable lymph nodes less than 4 cm in diameter. Categorical variables are shown as percentages and frequencies whereas continuous variables as mean and range. Results: From 2006 to 2020, 210 VEIL procedures were performed in 105 patients. Mean age was 58 (45-68) years old. Mean operative time was 90 minutes (60-120). Mean lymph node yield was 10 nodes (6-16). Complication rate was 15.7%, including severe complications in 1.9% of procedures. Lymphatic and skin complications were noted in 8.6 and 4.8% of patients, respectively. Histopathological analysis revealed lymph node involvement in 26.7% of patients with non-palpable nodes. Inguinal recurrence was observed in 2.8% of patients. 10y- overall survival was 74.2% and 10-y cancer specific survival was 84.8%. CSS for pN0, pN1, pN2 and pN3 were 100%, 82.4%, 72.7% and 9.1%, respectively. Conclusion: VEIL seems to offer appropriate long term oncological control with minimal morbidity. In the absence of non-invasive stratification measures such as dynamic sentinel node biopsy, VEIL emerged as the alternative for the management of non-bulky lymph nodes in penile cancer.

Advances in pheochromocytoma management in the era of laparoscopy.

PURPOSE: To understand the advances that were made in the management of pheochromocytoma since laparoscopy was initiated at our institution. MATERIALS AND METHODS: Data for all patients who underwent surgical procedure for adrenal diseases had been recorded prospectively since September 2000, when laparoscopy was routinely initiated at our institution; all patients with a diagnosis of pheochromocytoma up to December 2005 had their data assessed (group 1). Charts for all patients with a diagnosis of pheochromocytoma who underwent surgery at our institution from 1990 to 1995 (group 2) were reviewed, and the data were compared with data from patients in group 1. RESULTS: In group 1, 24 patients with pheochromocytoma underwent 26 procedures at our institution, including five patients with extra-adrenal tumor and one patient with bilateral tumor; 18 adrenalectomies (one bilateral) were performed, and two extra-adrenal tumors were removed using a laparoscopic approach. In group 2, ten open adrenalectomies were performed in 9 patients (1 bilateral). The patients who underwent laparoscopy for either adrenal or extra-adrenal tumor had shorter operative times and hospital stay and less bleeding. CONCLUSIONS: Pheochromocytoma is a complex disease with potentially severe complications. Laparoscopic adrenalectomy can be safely performed for removal of either adrenal or extra-adrenal tumors. Patients spend a shorter time in the critical care unit after the procedure.

Evaluation of renal defect healing, hemostasis, and urinary fistula after laparoscopic partial nephrectomy with oxidized cellulose.

BACKGROUND AND PURPOSE: Laparoscopic partial nephrectomy (LPN) has been performed at several institutions using oxidized cellulose (OC) as a means of bleeding and urinary fistula (UF) prevention. However, a foreign-body reaction mimicking either abscess or tumor recurrence has been associated with the use of OC. We evaluated renal-defect healing after LPN with and without OC. MATERIALS AND METHODS: Sixteen female Landrace pigs underwent lower-pole excision; all the collecting systems were entered and then closed with absorbable running suture. In group 1, hemostatic U-shaped stitches were the only method of hemostasis. In group 2, a bolster of OC was added to the renal defect. The pigs were sacrificed at 1, 4, 7, or 21 days, and gross findings such as perirenal collection were observed. A catheter was advanced up to the kidney, and methylene blue was injected with collecting system pressure observation; burst pressure was defined as the appearance of extravasation. High risk for UF was defined as burst pressure <10 mm Hg. RESULTS: Neither hemorrhage nor urinoma was observed during sacrifice. One pig from group 2 had a burst pressure of 4 mm Hg At 7 days (high risk for UF). At 21 days in group 2, the tissue was grossly solid, apparently a granuloma. Suppuration tended to be greater in group 2. The foreign-body reaction was more intense in group 2 and was strongly present at 4, 7, and 21 days. CONCLUSIONS: The use of OC is associated with higher scores of suppuration and foreign-body reaction. After LPN with OC, postoperative day 7 might be a critical time for the development of urinary leakage.

Multidimensional integrative analysis uncovers driver candidates and biomarkers in penile carcinoma.

Molecular data generation and their combination in penile carcinomas (PeCa), a significant public health problem in poor and underdeveloped countries, remain virtually unexplored. An integrativemethodology combin ing genome-wide copy number alteration, DNA methylation, miRNA and mRNA expression analysis was performed in a set of 20 usual PeCa. The well-ranked 16 driver candidates harboring genomic alterations and regulated by a set of miRNAs, including hsa-miR-31, hsa-miR-34a and hsa-miR-130b, were significantly associated with over-represented pathways in cancer, such as immune-inflammatory system, apoptosis and cell cycle. Modules of co-expressed genes generated from expression matrix were associated with driver candidates and classified according to the over-representation of passengers, thus suggesting an alteration of the pathway dynamics during the carcinogenesis. This association resulted in 10 top driver candidates (AR, BIRC5, DNMT3B, ERBB4, FGFR1, PML, PPARG, RB1, TNFSF10 and STAT1) selected and confirmed as altered in an independent set of 33 PeCa samples. In addition to the potential driver genes herein described, shorter overall survival was associated with BIRC5 and DNMT3B overexpression (log-rank test, P = 0.026 and P = 0.002, respectively) highlighting its potential as novel prognostic marker for penile cancer.

Integrative miRNA and mRNA analysis in penile carcinomas reveals markers and pathways with potential clinical impact.

Penile carcinoma (PeCa) is an important public health issue in poor and developing countries, and has only recently been explored in terms of genetic and epigenetic studies. Integrative data analysis is a powerful method for the identification of molecular drivers involved in cancer development and progression. miRNA and mRNA expression profiles followed by integrative analysis were investigated in 23 PeCa and 12 non-neoplastic penile tissues (NPT). Expression levels of eight miRNAs and 10 mRNAs were evaluated in the same set of samples used for microarray and in a validation set of cases (PeCa = 36; NPT = 27). Eighty-one miRNAs and 2,697 mRNAs were identified as differentially expressed in PeCa. Integrative data analysis revealed 255 mRNAs potentially regulated by 68 miRNAs. Using RT-qPCR, eight miRNAs and nine transcripts were confirmed as altered in PeCa. We identified that MMP1, MMP12 and PPARG and hsa-miR-31-5p, hsa-miR-224-5p, and hsa-miR-223-3p were able to distinguish tumors from NPT with high sensitivity and specificity. Higher MMP1 expression was detected as a better predictor of lymph node metastasis than the clinical-pathological data. In addition, PPARG and EGFR were highlighted as potential pathways for targeted therapy in PeCa. The analysis based on HPV positivity (7 of 23 cases) revealed five miRNA and 13 mRNA differentially expressed. Although in a limited number of cases, HPV positive PeCa presented less aggressive phenotype in comparison with negative cases. Overall, an integrative analysis using mRNA and miRNA profiles revealed markers related with tumor development and progression. Furthermore, MMP1 expression level was a predictive marker for lymph node metastasis in patients with PeCa.