The clinical meaning of lymphovascular invasion: preoperative predictors and postoperative implications in prostate cancer - a retrospective study.

Introduction: Lymphovascular invasion (LVI) is a pivotal histopathological parameter in prostate cancer (PCa), holding significant prognostic implications. Our study pursued a dual objective: firstly, to identify preoperative factors associated with LVI, aiming to unveil markers facilitating the recognition of patients prone to LVI during postoperative examination; and secondly, to assess postoperative outcomes correlated with LVI. Methods: We retrospectively analyzed 861 nonmetastatic PCa patients who underwent radical prostatectomy (RP), investigating preoperative factors and postoperative outcomes. Surgical specimens were processed following established guidelines. Statistical analyses utilized non-parametric tests to assess the association between LVI and both pre- and postoperative factors. Furthermore, logistic regression analyses were utilized to develop models aimed at identifying the most significant predictors of LVI and pN1 status, respectively. Results: Numerous preoperative factors exhibited significant correlations with LVI, offering valuable clinical insights. Logistic regression identified magnetic resonance imaging (MRI)-based clinical tumor stage (cT) 3-4, biopsy Gleason Grading Group (GGG) 3-5, preoperative prostate specific antigen (PSA) ≥20 and percentage of positive biopsy cores (PPBC) ≥50% as the strongest preoperative predictors of LVI. Additionally, the study uncovered an association between LVI and postoperative outcomes, including postoperative PSA (p value <0.001), extracapsular extension (ECE) (<0.001), positive surgical margins (PSM) (<0.001), perineural invasion (PNI) (<0.001), pathological tumor stage (pT) (<0.001), pathological lymph node status (pN) (<0.001), postoperative GGG (<0.001), and operative time (0.023). Notably, the study revealed a novel and substantial association between LVI and an increased number of positive lymph nodes in pN+ patients in the univariate analysis (<0.001). Furthermore, we have found an association between LVI and pN1 status in the logistic regression analysis (odds ratio [OR] = 23.905; p <0.001). Conclusion: Our findings underscore the pivotal role of LVI in influencing the prognosis of prostate cancer (PCa). The study acknowledges the challenges associated with preoperative LVI assessment and emphasizes the need for future research to unravel the factors associated with this histopathological finding. Significantly, our research stands out as the first, to the best of our knowledge, to reveal the association between LVI and the number of positive lymph nodes in pN+ patients.

Lymph Node Dissection in Testicular Cancer: The State of the Art and Future Perspectives.

PURPOSE OF REVIEW: This narrative review provides a comprehensive overview of the evolving role of retroperitoneal lymph node dissection (RPLND) in the management of testicular cancer (TC). It explores the significance of RPLND as both a diagnostic and therapeutic tool, highlighting its contribution to accurate staging, its impact on oncological outcomes, and its influence on subsequent treatment decisions. RECENT FINDINGS: RPLND serves as an essential diagnostic procedure, aiding in the precise assessment of lymph node involvement and guiding personalized treatment strategies. It has demonstrated therapeutic value, particularly in patients with specific risk factors and disease stages, contributing to improved oncological outcomes and survival rates. Recent studies have emphasized the importance of meticulous patient selection and nerve-sparing techniques to mitigate complications while optimizing outcomes. Additionally, modern imaging and surgical approaches have expanded the potential applications of RPLND. In the context of TC management, RPLND remains a valuable and evolving tool. Its dual role in staging and therapy underscores its relevance in contemporary urological practice. This review highlights the critical role of RPLND in enhancing patient care and shaping treatment strategies, emphasizing the need for further research to refine patient selection and surgical techniques.

Association of Lymphovascular Invasion with Lymph Node Metastases in Prostate Cancer-Lateralization Concept.

BACKGROUND: Lymphovascular invasion (LVI) is a vital but often overlooked prognostic factor in prostate cancer. As debates on lymphadenectomy's overtreatment emerge, understanding LVI laterality gains importance. This study pioneers the investigation into PCa, aiming to uncover patterns that could influence tailored surgical strategies in the future. METHODS: Data from 96 patients with both LVI and lymph node invasion (LNI) were retrospectively analyzed. All participants underwent radical prostatectomy (RP) with modified-extended pelvic lymph node dissection (mePLND). All specimens underwent histopathological examination. The assessment of LVI was conducted separately for the right and left lobes of the prostate. Associations within subgroups were assessed using U-Mann-Whitney and Kruskal-Wallis tests, as well as Kendall's tau-b coefficient, yielding p-values and odds ratios (ORs). RESULTS: Out of the 96 patients, 61 (63.5%) exhibited exclusive left-sided lymphovascular invasion (LVI), 24 (25.0%) had exclusive right-sided LVI, and 11 (11.5%) showed bilateral LVI. Regarding nodal involvement, 23 patients (24.0%) had LNI solely on the left, 25 (26.0%) exclusively on the right, and 48 (50.0%) on both sides. A significant correlation was observed between lateralized LVI and lateralized LNI (p < 0.001), particularly in patients with right-sided LVI only. LN-positive patients with left-sided LVI tended to have higher pT stages (p = 0.047) and increased odds ratios (OR) of bilateral LNI (OR = 2.795; 95% confidence interval [CI]: 1.231-6.348) compared to those with exclusive right-sided LVI (OR = 0.692; 95% CI: 0.525-0.913). CONCLUSIONS: Unilateral LVI correlates with ipsilateral LNI in PCa patients with positive LNs, notably in cases of exclusively right-sided LVI. Left-sided LVI associates with higher pT stages and a higher percentage of bilateral LNI cases.

Preoperative Factors for Lymphovascular Invasion in Prostate Cancer: A Systematic Review and Meta-Analysis.

Lymphovascular invasion (LVI) is one of the most important prognostic factors in prostate cancer (PCa) and is correlated with worse survival rates, biochemical recurrence (BCR), and lymph node metastasis (LNM). The ability to predict LVI preoperatively in PCa may be useful for proposing variations in the diagnosis and management strategies. We performed a systematic review and meta-analysis to identify preoperative clinicopathological factors that correlate with LVI in final histopathological specimens in PCa patients. Systematic literature searches of PubMed, Embase, and Web of Science were performed up to 31 January 2023. A total of thirty-nine studies including 389,918 patients were included, most of which were retrospective and single-center. PSA level, clinical T stage, and biopsy Gleason score were significantly correlated with LVI in PCa specimens. Meta-analyses revealed that these factors were the strongest predictors of LVI in PCa patients. Prostate volume, BMI, and age were not significant predictors of LVI. A multitude of preoperative factors correlate with LVI in final histopathology. Meta-analyses confirmed correlation of LVI in final histopathology with higher preoperative PSA, clinical T stage, and biopsy Gleason score. This study implies advancements in risk stratification and enhanced clinical decision-making, and it underscores the importance of future research dedicated to validation and exploration of contemporary risk factors in PCa.

Coexistence of Ehlers-Danlos Syndrome with Coronary-Pulmonary Arterial Fistula and Other Multiple Coronary Artery Anomalies.

This case report presents a 34-year-old male with Ehlers-Danlos syndrome, type 2 diabetes mellitus, aortic valve regurgitation, and aortic bulb aneurysm. Following spine surgery for thoracic-lumbar stabilization, the patient underwent assessment for aortic bulb aneurysm and aortic valve replacement surgeries. Five months post spinal surgery, a coronary computed tomography angiography was performed. The coronary computed tomography angiography revealed unique findings, including the absence of the left main coronary artery, right coronary artery dominance, ectopic origin of the left circumflex artery from the right sinus of the valsalva, a coronary-pulmonary arterial fistula originating from the right sinus of the valsalva, and an additional right pulmonary vein. The patient was qualified for surgical treatment for an aortic bulb aneurysm, was informed about the high surgical risk, and is awaiting surgery. This case underscores the rarity of Ehlers-Danlos syndrome coexisting with multiple coronary artery anomalies. The presence of a coronary-pulmonary arterial fistula further emphasizes the need for specialized patient monitoring when Ehlers-Danlos syndrome and coronary anomalies converge.

Lymph Node Dissection in Upper Tract Urothelial Carcinoma: Current Status and Future Perspectives.

PURPOSE OF REVIEW: This narrative review aims to evaluate the role of lymph node dissection (LND) in upper tract urothelial carcinoma (UTUC) and its implications for staging and management outcomes, as well as future perspectives. RECENT FINDINGS: Multiple studies have demonstrated the limitations of conventional imaging techniques in accurately localizing lymph node metastasis (LNM) in UTUC. While 18F-fluorodeoxyglucose positron emission tomography with computed tomography (18FDG-PET/CT) shows promise for preoperative LNM detection, its specificity is low. Alternative methods such as choline PET/CT and sentinel lymph node detection are under consideration but require further investigation. Additionally, various preoperative factors associated with LNM hold potential for predicting nodal involvement, thereby improving nodal staging and oncologic outcomes of LND. Several surgical approaches, including segmental ureterectomy and robot-assisted nephroureterectomy, provide a possibility for LND, while minimizing morbidity. LND remains the primary nodal staging tool for UTUC, but its therapeutic benefit is still uncertain. Advances in imaging techniques and preoperative risk assessment show promise in improving LNM detection. Further research and multi-center studies are needed to comprehensively assess the advantages and limitations of LND in UTUC, as well as the long-term outcomes of alternative staging and treatment strategies.

Sentinel Lymph Node Techniques in Urologic Oncology: Current Knowledge and Application.

Lymph node (LN) metastases have a significant negative impact on the prognosis of urological malignancies. Unfortunately, current imaging modalities are insufficient when it comes to detecting micrometastases; thus, surgical LN removal is commonly used. However, there is still no established ideal lymph node dissection (LND) template, leading to unnecessary invasive staging and the possibility of missing LN metastases located outside the standard template. To address this issue, the sentinel lymph node (SLN) concept has been proposed. This technique involves identifying and removing the first group of draining LNs, which can accurately stage cancer. While successful in breast cancer and melanoma, the SLN technique in urologic oncology is still considered experimental due to high false-negative rates and lack of data in prostate, bladder, and kidney cancer. Nevertheless, the development of new tracers, imaging modalities, and surgical techniques may improve the potential of the SLN procedures in urological oncology. In this review, we aim to discuss the current knowledge and future contributions of the SLN procedure in the management of urological malignancies.

Management of Bladder Cancer Patients with Clinical Evidence of Lymph Node Invasion (cN+).

The purpose of this review is to present the current knowledge about the diagnostic and treatment options for bladder cancer (BCa) patients with clinically positive lymph nodes (cN+). This review shows compaction of CT and MRI performance in preoperative prediction of lymph node invasion (LNI) in BCa patients, along with other diagnostic methods. Most scientific societies do not distinguish cN+ patients in their guidelines; recommendations concern muscle-invasive bladder cancer (MIBC) and differ between associations. The curative treatment that provides the best long-term survival in cN+ patients is a multimodal approach, with a combination of neoadjuvant chemotherapy (NAC) and radical cystectomy (RC) with extended pelvic lymph node dissection (ePLND). The role of adjuvant chemotherapy (AC) remains uncertain; however, emerging evidence indicates comparable outcomes to NAC. Therefore, in cN+ patients who have not received NAC, AC should be implemented. The response to ChT is a crucial prognostic factor for cN+ patients. Recent studies demonstrated the growing importance of immunotherapy, especially in ChT-ineligible patients. Moreover, immunotherapy can be suitable as adjuvant therapy in selected cases. In cN+ patients, the extended template of PLND should be utilized, with the total resected node count being less important than the template. This review is intended to draw special attention to cN+ BCa patients, as the oncological outcomes are significantly worse for this group.

Diagnostic Value of Radio-Guided Sentinel Node Detection in Patients with Prostate Cancer Undergoing Radical Prostatectomy with Modified-Extended Lymphadenectomy.

Background. In many malignancies, sentinel lymph node dissection (SLND) is being used as a nodal staging tool. We prospectively evaluated the diagnostic value of radio-guided sentinel lymph node (SLN) detection in patients with prostate cancer (PCa). This study aimed to investigate the reliability of the radio-guided SLN detection technique for perioperative localization of LNs metastases as well as to map lymphatic drainage patterns of the prostate. Methods. Forty-three patients with intermediate- or high-risk cN0cM0 PCa at conventional imaging underwent radical prostatectomy with modified-extended pelvic lymph node dissection (mePLND). A day before the planned surgery, a Tc-99m nanocolloid was injected into the prostate under the control of transrectal ultrasonography (TRUS). Preoperative single-photon emission computed tomography (SPECT-CT) imaging and intraoperative gamma-probe were used to identify SLNs. All positive lesions were excised, followed by mePLND. The excised lymph nodes (LNs) were then submitted for histopathological examination, which was used as a reference for the calculation of diagnostic parameters of the SLN technique for SPECT-CT and the intraoperative gamma-probe. Results. In total, 119 SLNs were detected preoperatively (SPECT-CT) and 118 intraoperatively (gamma-probe). The study revealed that both SLN detection techniques showed a sensitivity of 90% and a specificity of 6.06%. The negative predictive value (NPV) was 66.67%. SLN technique would have correctly staged nine of 10 patients, which is the same result as in the case of limited LND. However, it allowed the removal of all metastatic nodes only in four of them. SLND would have comprised 69.7% of preoperatively detected LNs, and removed 13 out of 19 positive LNs (68.42%), respectively. Conclusions. Radio-guided SLND has a low diagnostic rate and is a poor staging tool. ePLND remains the gold standard in nodal metastases assessment in PCa. Our study indicates that lymphatic drainage of the prostate and actual metastasis routes may vary significantly.

Boosting the Immune Response-Combining Local and Immune Therapy for Prostate Cancer Treatment.

Due to its slow progression and susceptibility to radical forms of treatment, low-grade PC is associated with high overall survival (OS). With the clinical progression of PC, the therapy is becoming more complex. The immunosuppressive tumor microenvironment (TME) makes PC a difficult target for most immunotherapeutics. Its general immune resistance is established by e.g., immune evasion through Treg cells, synthesis of immunosuppressive mediators, and the defective expression of surface neoantigens. The success of sipuleucel-T in clinical trials initiated several other clinical studies that specifically target the immune escape of tumors and eliminate the immunosuppressive properties of the TME. In the settings of PC treatment, this can be commonly achieved with radiation therapy (RT). In addition, focal therapies usually applied for localized PC, such as high-intensity focused ultrasound (HIFU) therapy, cryotherapy, photodynamic therapy (PDT), and irreversible electroporation (IRE) were shown to boost the anti-cancer response. Nevertheless, the present guidelines restrict their application to the context of a clinical trial or a prospective cohort study. This review explains how RT and focal therapies enhance the immune response. We also provide data supporting the combination of RT and focal treatments with immune therapies.

Patients with Positive Lymph Nodes after Radical Prostatectomy and Pelvic Lymphadenectomy-Do We Know the Proper Way of Management?

Lymph node invasion in prostate cancer is a significant prognostic factor indicating worse prognosis. While it significantly affects both survival rates and recurrence, proper management remains a controversial and unsolved issue. The thorough evaluation of risk factors associated with nodal involvement, such as lymph node density or extracapsular extension, is crucial to establish the potential expansion of the disease and to substratify patients clinically. There are multiple strategies that may be employed for patients with positive lymph nodes. Nowadays, therapeutic methods are generally based on observation, radiotherapy, and androgen deprivation therapy. However, the current guidelines are incoherent in terms of the most effective management approach. Future management strategies are expected to make use of novel diagnostic tools and therapies, such as photodynamic therapy or diagnostic imaging with prostate-specific membrane antigen. Nevertheless, this heterogeneous group of men remains a great therapeutic concern, and both the clarification of the guidelines and the optimal substratification of patients are required.

Using Milk Thistle (Silybum marianum) Extract to Improve the Welfare, Growth Performance and Meat Quality of Broiler Chicken.

Modern poultry production looks for feed and water additives that improve the welfare of chickens. The utilization of herbs as additives in feed or drinking water is becoming increasingly well known. The aim of this study was to determine the effect of milk thistle extract (Silybum marianum), administered in drinking water, on chickens' welfare, production results, selected physicochemical properties of the breast muscles, the activity of selected enzymes, and the antioxidant potential of blood serum and breast muscles. A total of 102 one-day-old male ROSS 308 chicks were allocated into three treatment groups. The material was an infusion of dried milk thistle seeds in two doses, administered in drinking water for chickens (group: C = 0; E1 = 0.24; E2 = 0.36 g/day/animal) under standard rearing conditions. As a result of adding the milk thistle to the drinking water, there was an improvement in the welfare of the chickens and in the production results, enzymatic capacity of selected enzymes, and antioxidant capacity in the blood serum and in pectoral muscle (p ≤ 0.05). The addition of a milk thistle seed infusion for chickens can be used in poultry production to improve the rearing performance antioxidant capacity and welfare of chickens.

Utility of Lymphadenectomy in Prostate Cancer: Where Do We Stand?

The purpose of this review is to summarize the current knowledge on lymph node dissection (LND) in prostate cancer (PCa) patients undergoing radical prostatectomy (RP). Despite a growing body of evidence, the utility and therapeutic and prognostic value of such an approach, as well as the optimal extent of LND, remain unsolved issues. Although LND is the most accurate staging procedure, the direct therapeutic effect is still not evident from the current literature, which limits the possibility of establishing clear recommendations. This indicates the need for further robust and adequately designed high-quality clinical trials.