miRNA and mRNA Expression Profiles Associated with Lymph Node Metastasis and Prognosis in Penile Carcinoma.

Penile cancer (PeC) is a rare disease, and no prognostic biomarkers have been adopted in clinical practice yet. The objective of the present study was to identify differentially expressed miRNAs (DEmiRs) and genes (DEGs) as potential biomarkers for lymph node metastasis and other prognostic factors in PeC. Tumor samples were prospectively obtained from 24 patients with squamous cell carcinoma of the penis. miRNA microarray analysis was performed comparing tumors from patients with inguinal lymph node metastatic and localized disease, and the results were validated by qRT-PCR. Eighty-three gene expression levels were also compared between groups through qRT-PCR. Moreover, DEmiRs and DEGs expression levels were correlated with clinicopathological variables, cancer-specific (CSS), and overall survival (OS). TAC software, TM4 MeV 4.9 software, SPSS v.25.0, and R software v.4.0.2 were used for statistical analyses. We identified 21 DEmiRs in microarray analysis, and seven were selected for validation. miR-744-5p and miR-421 were overexpressed in tissue samples of metastatic patients, and high expression of miR-421 was also associated with lower OS. We found seven DEGs (CCND1, EGFR, ENTPD5, HOXA10, IGF1R, MYC, and SNAI2) related to metastatic disease. A significant association was found between increased MMP1 expression and tumor size, grade, pathological T stage, and perineural invasion. Other genes were also associated with clinicopathological variables, CSS and OS. Finally, we found changes in mRNA-miRNA regulation that contribute to understanding the mechanisms involved in tumor progression. Therefore, we identified miRNA and mRNA expression profiles as potential biomarkers associated with lymph node metastasis and prognosis in PeC, in addition to disruption in mRNA-miRNA regulation during disease progression.

MicroRNA-23b and microRNA-27b plus flutamide treatment enhances apoptosis rate and decreases CCNG1 expression in a castration-resistant prostate cancer cell line.

The acquisition of a castration-resistant prostate cancer phenotype by prostate cancer cells is the alteration that has the worst prognosis for patients. The aim of this study was to evaluate the role of the microRNAs-23b/-27b as well as the possible CCNG1 target gene in tissue samples from patients with localized prostate cancer that progressed to castration-resistant prostate cancer and in a castration-resistant prostate cancer cell line (PC-3). The microRNAs and target gene expression levels of the surgical specimens were analyzed by quantitative real-time polymerase chain reaction. The prostate cancer cell line, PC-3, was transfected with pre-miR-23b, pre-miR-27b, and their respective controls using Lipofectamine RNAiMAX and exposed or not to flutamide. After transfections, expression levels of both the microRNAs and the gene, CCNG1, were analyzed by quantitative real-time polymerase chain reaction. The apoptosis and cell cycle assays were performed on the mini MUSE cytometer. MicroRNAs-23b/-27b were underexpressed in surgical specimens of prostate cancer; however, their target gene, CCNG1, was overexpressed in 69% of the cases. After transfection with the microRNAs-23b/-27b and flutamide, we observed a reduction in gene expression compared with cells that were treated only with microRNAs or only with flutamide. In the apoptosis assay, we demonstrated cell sensitization following transfection with microRNAs-23b/-27b and potentiation when co-administered with flutamide. The number of cells in apoptosis was almost three times higher with the simultaneous treatments (miR + flutamide) compared with the control (p < 0.05). In the cell cycle assay, only flutamide treatment showed better results; a higher number of cells were found in the G0-G1 phase, and a lower percentage of cells completed the final phase of the cycle (p < 0.05). We conclude that microRNAs-23b/-27b are downexpressed in prostate cancer, and their target gene, CCNG1, is overexpressed. We postulated that microRNAs-23b/-27b sensitize the PC-3 cell line and that after the addition of flutamide in the apoptosis assay, we would observe synergism in the treatments between miR and flutamide. In the cell cycle assay, the use of flutamide was sufficient to decrease the number of cells in mitosis. Therefore, we postulate that microRNAs, along with other drugs, may become very useful therapeutic tools in the treatment of castration-resistant prostate cancer.

Predictive factors for prolonged hospital stay after retropubic radical prostatectomy in a high-volume teaching center.

OBJECTIVE: To evaluate the length hospital stay and predictors of prolonged hospitalization after RRP performed in a high-surgical volume teaching institution, and analyze the rate of unplanned visits to the office, emergency care, hospital readmissions and perioperative complications rates. MATERIALS AND METHODS: Retrospective analysis of prospectively collected data in a standardized database for patients with localized prostate cancer undergoing RRP in our institution between January/2010 - January/2012. A logistic regression model including preoperative variables was initially built in order to determine the factors that predict prolonged hospital stay before the surgical procedure; subsequently, a second model including both pre and intraoperative variables was analyzed. RESULTS: 1011 patients underwent RRP at our institution were evaluated. The median hospital stay was 2 days, and 217 (21.5%) patients had prolonged hospitalization. Predictors of prolonged hospital stay among the preoperative variables were ICC (OR. 1.40 p=0.003), age (OR 1.050 p<0.001), ASA score of 3 (OR. 3.260 p<0.001), prostate volume on USG-TR (OR, 1.005 p=0.038) and African-American race (OR 2.235 p=0.004); among intra and postoperative factors, operative time (OR 1.007 p=0.022) and the presence of any complications (OR 2.013 p=0.009) or major complications (OR 2.357 p=0.01) were also correlated independently with prolonged hospital stay. The complication rate was 14.5%. CONCLUSIONS: The independent predictors of prolonged hospitalization among preoperative variables were CCI, age, ASA score of 3, prostate volume on USG-TR and African-American race; amongst intra and postoperative factors, operative time, presence of any complications and major complications were correlated independently with prolonged hospital stay.

Determinism, chaos, self-organization and entropy.

We discuss two changes of paradigms that occurred in science along the XXth century: the end of the mechanist determinism, and the end of the apparent incompatibility between biology, where emergence of order is law, and physics, postulating a progressive loss of order in natural systems. We recognize today that three mechanisms play a major role in the building of order: the nonlinear nature of most evolution laws, along with distance to equilibrium, and with the new paradigm, that emerged in the last forty years, as we recognize that networks present collective order properties not found in the individual nodes. We also address the result presented by Blumenfeld (L.A. Blumenfeld, Problems of Biological Physics, Springer, Berlin, 1981) showing that entropy decreases resulting from building one of the most complex biological structures, the human being, are small and may be trivially compensated for compliance with thermodynamics. Life is made at the expense of very low thermodynamic cost, so thermodynamics does not pose major restrictions to the emergence of life. Besides, entropy does not capture our idea of order in biological systems. The above questions show that science is not free of confl icts and backlashes, often resulting from excessive extrapolations.

Successful equine in vitro embryo production by ICSI - effect of season, mares' age, breed, and phase of the estrous cycle on embryo production.

This retrospective study aimed at identifying factors that contribute to the success of equine in vitro embryo production by intracytoplasmic sperm injection (ICSI). A total of 7993 ovum pick-up (OPU) sessions were performed, totaling 2540 donor mares and semen from 396 stallions. Oocytes were aspirated at multiple sites in Brazil and were sent to the laboratory, within 6 h from OPU, in pre-maturation medium where they were in vitro matured (IVM) followed by ICSI and in vitro embryo culture for 7-8 days. The number of recovered oocytes, matured oocytes, cleaved embryos and blastocysts were used to explore the effect of age and breed of the donor mare, time of year in which the mare was aspirated and phase of the estrous cycle on the day of follicular aspiration. Mares between 6 and 15 years old were superior to other age groups in most parameters evaluated, including the average number of blastocysts per OPU. The impact of age was similar when evaluated within two breeds, American Quarter Horse (AQHA) and Warmblood mares. We observed that breed (AQHA, Warmblood, Crioulo, Lusitano and Mangalarga) had an important effect on most of the parameter evaluated, including number of oocytes recovered, blastocysts produced per OPU, and blastocyst rates. The overall impact of season was less pronounced than age and breed, with the only statistically significant difference being a higher rate of oocyte maturation during the summer season. Finally, most of the parameters evaluated were superior in follicular phase mares, with or without dominant follicle than luteal phase mares. In conclusion, this retrospective study revealed that breed, age, season and stage of estrous at the time of OPU are all important parameters for the success of equine embryo production by ICSI. This technology enables producing embryos all-year-round from mares of different breeds and ages from OPU-derived oocytes collected at multiple sites.

Can single positive core prostate cancer at biopsy be considered a low-risk disease after radical prostatectomy?

PURPOSE: Single positive core in a prostate biopsy is usually associated with indolent prostate cancer (PCa) and is one of the active surveillance (AS) inclusion criteria. We investigated whether single positive core PCa at biopsy could define an archetype of low-risk disease. MATERIALS AND METHODS: A total of 1320 consecutive patients were enrolled. Among them, 249 patients with single positive core PCa were followed up, and the clinical and pathological parameters influencing prognosis were analyzed. RESULTS: Out of the 249 patients, 172 (69.0%) had pathological findings ≥ pT2c and 87 (34.9%) had an undergraded Gleason Score (GS) based on the biopsy. Positive surgical margins (PSMs), extraprostatic extension (EPE) and seminal vesicle invasion (SVI) were found in 20.8%, 10.0% and 6.0% of patients, respectively. In a comparative analysis, we found that the PSA level, prostate weight and number of cores at biopsy are essential to correctly predict an indolent PCa. A total of 125 patients (67.3%) with nonpalpable tumors became high-risk tumors (pT2c-T3). Analyzing only nonpalpable tumors with a GS of 6 at biopsy (156 patients), we noted that 106 (67.9% of cT1) progressed from cT1c to pT2c-pT3. CONCLUSIONS: Single core PCa have clinically significant disease in the Radical Prostatectomy specimens, with considerable rates of overgrading for the GS, pT2c-pT3, PSMs, EPE and SVI. The treatment plan must be evaluated individually for patients with single core PCa and must take into account other prognostic factors when determining whether a patient should be managed with AS.

Effect of inducing accessory corpus luteum formation with gonadotropin-releasing hormone or human chorionic gonadotropin on the day of embryo transfer on fertility of recipient dairy heifers and lactating cows.

The objective was to determine the effect of inducing an accessory corpus luteum (CL) using GnRH or human chorionic gonadotropin (hCG) on the day of in vitro-produced (IVP) embryo transfer (ET) on pregnancy per ET (P/ET) and calving/ET in dairy heifers and lactating cows. Dairy heifers (11-15 mo of age; n = 1,547) and lactating cows (n = 1,480) detected in estrus by tail chalk (d 0) were used as recipients. Before ET, the presence of a CL was evaluated by transrectal palpation from d 6 to 9 of the estrous cycle. Animals with a CL were randomly assigned to receive 1 of 3 treatments immediately before ET: control (no treatment; n = 1,009), GnRH (86 µg of GnRH; n = 1,085) and hCG (2,500 IU; n = 1,069). Embryos were implanted in the uterine horn ipsilateral to the ovary with a CL (fresh IVP embryos, n = 2,544; vitrified IVP embryos n = 545; slow-freezing IVP embryos, n = 74). Pregnancy diagnosis was performed on d 37 ± 3 of gestation by transrectal palpation. Pregnancy loss data and calving records were collected from the dairy farm management software. Treatment did not affect P/ET, calving/ET, or pregnancy loss either overall or within parity. When treatments inducing CL formation were combined (GnRH + hCG), heifers tended to have greater P/ET than controls (67.7 vs. 63.5%, respectively). Yet, calving/ET were similar. Response variables were also analyzed within embryo type and parity. For heifers receiving stage 6 (blastocyst) fresh IVP embryos, hCG had greater P/ET than controls (74.5 vs. 51.1%, respectively). In addition, GnRH tended to have greater P/ET than controls (67.8 vs. 51.2%, respectively). However, calving/ET in heifers receiving blastocyst fresh IVP embryos was similar among treatments. When only stage 7 (expanded blastocyst) fresh IVP embryos were considered, primiparous GnRH cows had greater P/ET (59.3 vs. 47.1%) and calving/ET (48.6 vs. 38.1%) than hCG. Moreover, hCG showed decreased calving/ET compared with controls in primiparous cows transferred with expanded blastocyst fresh IVP embryos. In summary, the effects of hCG or GnRH at ET on P/ET and calving/ET were inconsistent according to different embryo characteristics (e.g., embryo stage) and parity of recipients. Furthermore, treatment did not improve the overall fertility outcomes for recipient animals receiving IVP embryos.

Disruption of miRNA-mRNA Networks Defines Novel Molecular Signatures for Penile Carcinogenesis.

Penile cancer (PeC) carcinogenesis is not fully understood, and no biomarkers are reported in clinical practice. We aimed to investigate molecular signatures based on miRNA and mRNA and perform an integrative analysis to identify molecular drivers and pathways for PeC development. Affymetrix miRNA microarray was used to identify differentially expressed miRNAs (DEmiRs) comparing 11 tumoral tissues (TT) paired with non-neoplastic tissues (NNT) with further validation in an independent cohort (n = 13). We also investigated the mRNA expression of 83 genes in the total sample. Experimentally validated targets of DEmiRs, miRNA-mRNA networks, and enriched pathways were evaluated in silico. Eight out of 69 DEmiRs identified by microarray analysis were validated by qRT-PCR (miR-145-5p, miR-432-5p, miR-487b-3p, miR-30a-5p, miR-200a-5p, miR-224-5p, miR-31-3p and miR-31-5p). Furthermore, 37 differentially expressed genes (DEGs) were identified when comparing TT and NNT. We identified four downregulated DEmiRs (miR-30a-5p, miR-432-5p, miR-487b-3p, and miR-145-5p) and six upregulated DEGs (IL1A, MCM2, MMP1, MMP12, SFN and VEGFA) as potential biomarkers in PeC by their capacity of discriminating TT and NNT with accuracy. The integration analysis showed eight dysregulated miRNA-mRNA pairs in penile carcinogenesis. Taken together, our findings contribute to a better understanding of the regulatory roles of miRNAs and altered transcripts levels in penile carcinogenesis.

Extended Versus Limited Pelvic Lymph Node Dissection During Radical Prostatectomy for Intermediate- and High-risk Prostate Cancer: Early Oncological Outcomes from a Randomized Phase 3 Trial.

BACKGROUND: The role of extended pelvic lymph node dissection (EPLND) in the surgical management of prostate cancer (PCa) patients remains controversial, mainly because of a lack of randomized controlled trials (RCTs). OBJECTIVE: To determine whether EPLND has better oncological outcomes than limited PLND (LPLND. DESIGN, SETTING AND PARTICIPANTS: This was a prospective, single-center phase 3 trial in patients with intermediate- or high-risk clinically localized PCa. INTERVENTION: Randomization (1:1) to LPLND (obturator nodes) or EPLND (obturator, external iliac, internal iliac, common iliac, and presacral nodes) bilaterally. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was biochemical recurrence-free survival (BRFS). Secondary outcomes were metastasis-free survival (MFS), cancer-specific survival (CSS), and histopathological findings. The trial was designed to show a minimal 15% advantage in 5-yr BRFS by EPLND. RESULTS AND LIMITATIONS: In total, 300 patients were randomized from May 2012 to December 2016 (150 LPLND and 150 EPLND). The median BRFS was 61.4 mo in the LPLND group and not reached in the EPLND group (hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.63-1.32; p = 0.6). Median MFS was not reached in either group (HR 0.57, 95% CI 0.17-1.8; p = 0.3). CSS data were not available because no patient died from PCa before the cutoff date. In exploratory subgroup analysis, patients with preoperative biopsy International Society of Urological Pathology (ISUP) grade groups 3-5 who were allocated to EPLND had better BRFS (HR 0.33, 95% CI 0.14-0.74, interaction p = 0.007). The short follow-up and surgeon heterogeneity are limitations to this study. CONCLUSION: This RCT confirms that EPLND provides better pathological staging, while differences in early oncological outcomes were not demonstrated. Our subgroup analysis suggests a potential BCRFS benefit in patients diagnosed with ISUP grade groups 3-5; however, these findings should be considered hypothesis-generating and further RCTs with larger cohorts and longer follow up are necessary to better define the role of EPLND during RP. PATIENT SUMMARY: In this study, we investigated early outcomes in prostate cancer patients undergoing prostatectomy according to the anatomic extent of lymph node resection. We found that extended removal of lymph nodes did not reduce biochemical recurrence of prostate cancer in the expected range.

Early Effects of High-intensity Focused Ultrasound (HIFU) Treatment for Prostate Cancer on Fecal Continence and Anorectal Physiology.

OBJECTIVE: To evaluate high-intensity focused ultrasound (HIFU) effects on anorectal physiology and fecal continence or constipation, and on quality of life (QoL). METHODS: We prospectively evaluated 26 patients with localized prostate cancer who underwent HIFU. The Rome III criteria for functional constipation, the Cleveland Clinic Florida Fecal Incontinence Score, and the Fecal Incontinence QoL Score questionnaires were answered before and after treatment. Anorectal manometry was used to evaluate resting and squeezing pressures, sustained contraction, paradoxical puborectalis contraction, rectal sensation, and rectal capacity. RESULTS: Thirteen patients underwent hemiablation and 13 underwent whole-gland ablation. There was no difference between groups regarding the Rome III criteria for functional constipation results. The Cleveland Clinic Florida Fecal Incontinence Score results showed that 3 (11.5%) of patients had mild fecal incontinence before HIFU and 5 (19.2%) had it afterward (P = .625). No patients reported poor QoL due to fecal incontinence in the Fecal Incontinence QoL Score. Anorectal manometry demonstrated no decrease in resting pressure after treatment (P = .299), while squeezing pressure significantly increased from 151.87 to 167.91 mm Hg (P = .034). The number of patients with normal sustained contraction remained the same (20 [77%]). Paradoxical puborectalis contraction was seen in 12 (46%) of the patients before the procedure and in 13 (50%) after (P = .713). Improvement in sensory parameters was not significant: first sense changed from 73.46 to 49.71 mL (P = .542) and first urge from 98.27 to 82.88 mL (P = .106). Rectal capacity had a nonsignificant decrease from 166.15 to 141.15mL (P = .073). CONCLUSION: HIFU did not cause significant changes in anorectal physiology. Fecal incontinence or constipation after HIFU was not observed via validated questionnaires.

Treatment of Localized and Locally Advanced, High-Risk Prostate Cancer: A Report From the First Prostate Cancer Consensus Conference for Developing Countries.

PURPOSE: To generate and present survey results on important issues relevant to treatment and follow-up of localized and locally advanced, high-risk prostate cancer (PCa) focusing on developing countries. METHODS: A panel of 99 PCa experts developed more than 300 survey questions of which 67 questions concern the main areas of interest of this article: treatment and follow-up of localized and locally advanced, high-risk PCa in developing countries. A larger panel of 99 international multidisciplinary cancer experts voted on these questions to create the recommendations for treatment and follow-up of localized and locally advanced, high-risk PCa in areas of limited resources discussed in this article. RESULTS: The panel voted publicly but anonymously on the predefined questions. Each question was deemed consensus if 75% or more of the full panel had selected a particular answer. These answers are based on panelist opinion and not on a literature review or meta-analysis. For questions that refer to an area of limited resources, the recommendations considered cost-effectiveness as well as the possible therapies with easier and greater access. Each question had five to seven relevant answers including two nonanswers. Results were tabulated in real time. CONCLUSION: The voting results and recommendations presented in this article can guide physicians managing localized and locally advanced, high-risk PCa in areas of limited resources. Individual clinical decision making should be supported by available data; however, as guidelines for treatment of localized and locally advanced, high-risk PCa in developing countries have not been defined, this article will serve as a point of reference when confronted with this disease.

Consensus on Prostate Cancer Treatment of Localized Disease With Very Low, Low, and Intermediate Risk: A Report From the First Prostate Cancer Consensus Conference for Developing Countries (PCCCDC).

PURPOSE: A group of international urology and medical oncology experts developed and completed a survey on prostate cancer (PCa) in developing countries. The results are reviewed and summarized, and recommendations on consensus statements for very low-, low-, and intermediate-risk PCa focused on developing countries were developed. METHODS: A panel of experts developed more than 300 survey questions of which 66 questions concern the principal areas of interest of this paper: very low, low, and intermediate risk of PCa in developing countries. A larger panel of 99 international multidisciplinary cancer experts voted on these questions to create the recommendations for treatment and follow-up for very low-, low-, and intermediate-risk PCa in areas of limited resources discussed in this manuscript. RESULTS: The panel voted publicly but anonymously on the predefined questions. Each question was deemed consensus if 75% or more of the full panel had selected a particular answer. These answers are based on panelist opinion not a literature review or meta-analysis. For questions that refer to an area of limited resources, the recommendations consider cost-effectiveness and the possible therapies with easier and greater access. Each question had five to seven relevant answers including two nonanswers. The results were tabulated in real time. CONCLUSION: The voting results and recommendations presented in this document can be used by physicians to support management for very low, low, and intermediate risk of PCa in areas of limited resources. Individual clinical decision making should be supported by available data; however, as guidelines for treatment for very low, low, and intermediate risk of PCa in developing countries have not been developed, this document will serve as a point of reference when confronted with this disease.

Single embryo and oocyte lipid fingerprinting by mass spectrometry.

Methods used for lipid analysis in embryos and oocytes usually involve selective lipid extraction from a pool of many samples followed by chemical manipulation, separation and characterization of individual components by chromatographic techniques. Herein we report direct analysis by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) of single and intact embryos or oocytes from various species. Biological samples were simply moisturized with the matrix solution and characteristic lipid (represented by phosphatidylcholines, sphingomyelins and triacylglycerols) profiles were obtained via MALDI-MS. As representative examples, human, bovine, sheep and fish oocytes, as well as bovine and insect embryos were analyzed. MALDI-MS is shown to be capable of providing characteristic lipid profiles of gametes and embryos and also to respond to modifications due to developmental stages and in vitro culture conditions of bovine embryos. Investigation in developmental biology of the biological roles of structural and reserve lipids in embryos and oocytes should therefore benefit from these rapid MALDI-MS profiles from single and intact species.

Oncologic Outcomes in Young Adults With Kidney Cancer Treated During the Targeted Therapy Era.

BACKGROUND: The objective of this study was to determine the outcomes of young adults with kidney cancer treated during the targeted therapy era and evaluate the impact of young age on survival. MATERIALS AND METHODS: We reviewed the records from 445 patients younger than 55 years with kidney cancer at a single institution from 2006 to 2017. Overall survival (OS) and recurrence-free survival were estimated with the Kaplan-Meier method and log-rank test. Cox proportional hazards regression was used to determine the impact of clinical and pathologic variables on all-cause mortality. RESULTS: Overall, 104 (23%) patients 40 years or younger were compared with 341 (77%) patients who were 41 to 55 years old. Younger patients presented with more advanced stages of the disease, including metastasis at diagnosis, positive lymph nodes, venous tumor thrombus and had more non-clear cell tumors (54% vs. 30%; P < .001). Young adults had significantly worse OS at 2 and 5 years (67% vs. 82% and 53% vs. 69%, respectively). Younger patients with metastatic disease received targeted agents less often compared with the older group (64% vs. 75%). There was no difference in recurrence-free survival across patients with localized disease. Independent prognostic factors associated with increased mortality were metastasis at diagnosis, pT2 or greater, and age younger than 40 years (hazard ratio, 1.65; 95% confidence interval, 1.0-2.6; P = .03). CONCLUSION: Patients younger than 40 years with kidney tumors treated during the targeted therapy era have worse OS compared with older adults. Young age is an independent predictor of mortality.

Genetic polymorphisms of matrix metalloproteinases: susceptibility and prognostic implications for prostate cancer.

PURPOSE: Prostate cancer is the most common tumor in males in Brazil. Single nucleotide polymorphisms have been demonstrated to exist in the promoter regions of matrix metalloproteinase genes and they are associated with the development and progression of some cancers. We investigated the correlation between MMP1, 2, 7 and 9 polymorphisms with susceptibility to prostate cancer, and classic prognostic parameters of prostate cancer. MATERIALS AND METHODS: Genomic DNA was extracted using conventional protocols. The DNA sequence containing the polymorphic site was amplified by real-time polymerase chain reaction using TaqMan(R) fluorescent probes. RESULTS: For the MMP1 gene the polymorphic allele was more common in the control group than in the prostate cancer group (p <0.001). For the MMP9 gene the incidence of the polymorphic homozygote genotype was higher in the prostate cancer group (p <0.001). For higher stage tumors (pT3) a polymorphic allele in the MMP2 gene was more common (p = 0.026). When considering Gleason score, the polymorphic homozygote genotype of MMP9 was more common in Gleason 6 or less tumors (p = 0.003), while a polymorphic allele in the MMP2 gene was more common in Gleason 7 or greater tumors (p = 0.042). CONCLUSIONS: MMP1 and MMP2 may protect against prostate cancer development and MMP9 may be related to higher risk. In contrast, MMP9 polymorphism was associated with a lower Gleason score and MMP2 polymorphism was associated with nonorgan confined disease.

Robot-assisted extended pelvic lymph node dissection in prostate cancer. When and how?

OBJECTIVE: To review the literature evaluating the role of the extended pelvic lymph node dissectione PLND during robot assisted radical prostatectomy (RARP) in the management of PCa patients, as well as the preoperative clinic pathologic factors that predict lymph node metastases (LNM). The technique and current outcomes of robotic ePLND will be presented. METHODS: Medline®/Pubmed® were searched up to august 2018 to find comparative studies of different anatomic limits of pelvic lymph node dissection (PLND) during RARP, open or pure laparoscopic surgery that reported number of nodes retrieved, oncologic outcomes and complications. The search was complemented to identify studies that evaluated diagnostic images and factors that predict LNM. Overall, 44 articles were included for full text review. RESULTS: There is not an imaging technique with an acceptable performance to select patients for PLND, the decision to perform a PLND is based on clinical characteristics described on validated nomograms. Median lymph node yield at RARP range from 5 to 21 depending on the extent of PLND, positivity rate of LN as high as 37% depending on the risk stratification of patients. Robot-assisted can be carried out to any extent with lymph node yields and safety concerns comparable to the open approach. CONCLUSION: Extended pelvic lymph node dissection is recommended to be performed at the time of RARP in intermediate and high-risk patients and cannot be replaced by other modalities. A benefit in terms of oncologic outcomes remains to be established. The robot assisted approach offers shorter length of hospital stay, lower transfusion rates and comparable outcomes compared to other surgical approaches.

ARTICULO SOLO EN INGLES.OBJETIVO: Revisar la literatura que evalúa  el papel de la linfadenectomía pélvica extendida  (LPe) durante la prostatectomía radical asistida por robot  (PRAR) en el manejo de pacientes con cáncer de próstata,  así como los factores clínico-patológicos preoperatorios  que predicen las metástasis ganglionares. Presentamos la técnica de LPe y sus resultados actuales.MÉTODOS: Se realizó una búsqueda bibliográfica en Medline®/Pubmed® hasta agosto 2018 para encontrar estudios comparativos de los diferentes límites anatómicos de la linfadenectomía pélvica duranteprostatectomía radical asistida por robot, abierta olaparoscópica que comunicaran número de ganglios,resultados oncológicos y complicaciones. La búsquedafue complementada para identificar estudios que evaluaran imágenes diagnósticas y factores predictivos demetástasis ganglionares. Finalmente, se incluyeron 44artículos. RESULTADOS: No hay una técnica de imagen que tengauna resolución aceptable para seleccionar pacientespara linfadenectomía. La decisión de practicar linfadenectomíase basa en las características clínicas descritasen nomogramas validados. La mediana del númerode ganglios obtenidos oscila entre 5 y 21 dependiendode la extensión de la linfadenectomía, y la tasa de gangliospositivos es tan alta como el 37% dependiendo dela estratificación del riesgo de los pacientes. La cirugíaasistida por robot puede realizarse con cualquier extensióncon un número de ganglios obtenidos y aspectosde seguridad comparables con el abordaje abierto. CONCLUSION: Se recomienda realizar la linfadenectomíapélvica extendida en el momento de la PRAR enpacientes de riesgo intermedio y alto y no puede reemplazarsepor otras modalidades. Sigue por establecerseun beneficio en términos de resultados oncológicos. Elabordaje asistido por robot ofrece estancias hospitalariasmás cortas, menores tasas de transfusión y resultadoscomparables en comparación con otros abordajesquirúrgicos.

Cdx2, cytokeratin 20, thyroid transcription factor 1, and prostate-specific antigen expression in unusual subtypes of prostate cancer.

There are some unusual histologic variants of prostate carcinoma, including mucinous, signet-ring cells, and ductal carcinomas that can metastasize in a problematic way and simulate lung, colorectal, or bladder primaries. Currently, antibodies that are organ-specific have been used in the routine surgical pathology practice. Our aim is to study the profile of expression of Cdx2, thyroid transcription factor 1 (TTF1), and cytokeratin 20 (CK20) in prostate cancer with unusual histologic finding. Twenty-nine prostate adenocarcinomas with unusual histologic findings were submitted to immunohistochemistry with prostate-specific antigen (PSA), CK20, Cdx2, and TTF1 antibodies. There were 7 mucinous, 5 ductal, 2 signet-ring cells, and 15 usual acinar adenocarcinomas with focal mucinous differentiation. To compare the results with usual acinar adenocarcinomas, we studied 10 primary and their respective lymph node metastases in a tissue microarray, 2 unusual metastatic adenocarcinomas, and 6 usual acinar high-grade carcinomas. For tumors with special histologic finding, Cdx2 was expressed by 9 (31.0%) mucinous, signet-cell, or with focal mucinous differentiation. Thyroid transcription factor 1 was moderately positive in mucinous differentiation areas of 2 (6.9%) adenocarcinomas. Cytokeratin 20 was expressed by 9 (31.0%) tumors, among them, 3 ductal adenocarcinomas. Prostate-specific antigen was positive in 28 (96.6%) cases and negative in 1 ductal adenocarcinoma. There was only 1 worrisome ductal adenocarcinoma that was strongly CK20 positive and PSA negative. Almost one third of mucinous prostate carcinomas express Cdx2. Cytokeratin 20 can be positive also in one third of prostate carcinomas, especially the ductal type. Pathologist should be alert when evaluating immunohistochemical profiles of unusual histologic findings of prostate cancer, mostly in distant sites.