Robotic-assisted vs. open ureteral reimplantation: a multicentre comparison.

PURPOSE: Open ureteral reimplantation is considered the standard surgical approach to treat distal ureteral strictures or injuries. These procedures are increasingly performed in a minimally invasive and robotic-assisted manner. Notably, no series comparing perioperative outcomes and safety of the open vs. robotic approach are available so far. METHODS: In this retrospective multi-center study, we compared data from 51 robotic ureteral reimplantations (RUR) with 79 open ureteral reimplantations (OUR). Both cohorts were comparatively assessed using different baseline characteristics and perioperative outcomes. Moreover, a multivariate logistic regression for independent predictors was performed. RESULTS: Surgery time, length of hospital stay and dwell time of bladder catheter were shorter in the robotic cohort, whereas estimated blood loss, postoperative blood transfusion rate and postoperative complications were lower than in the open cohort. In the multivariate linear regression analysis, robotic approach was an independent predictor for a shorter operation time (coefficient - 0.254, 95% confidence interval [CI] - 0.342 to - 0.166; p < 0.001), a lower estimated blood loss (coefficient - 0.390, 95% CI - 0.549 to - 0.231, p < 0.001) and a shorter length of hospital stay (coefficient - 0.455, 95% CI - 0.552 to - 0.358, p < 0.001). Moreover, robotic surgery was an independent predictor for a shorter dwell time of bladder catheter (coefficient - 0.210, 95% CI - 0.278 to - 0.142, p < 0.001). CONCLUSION: RUR represents a safe alternative to OUR, with a shorter operative time, decreased blood loss and length of hospital stay. Prospective research are needed to further define the extent of the advantages of the robotic approach over open surgery.

Current role of intraoperative cell salvage techniques in the management of renal tumors with level III and IV inferior vena cava thrombus extension.

Background: En bloc removal of the kidney with tumor thrombus excision in a multidisciplinary team remains the standard treatment for renal cell carcinoma (RCC) with tumor thrombus extension. In order to minimize the hemodynamic impact of the surgical blood loss, intraoperative cell salvage (IOCS) techniques can decrease the need for allogeneic blood and prevent blood transfusion related complications. Objective: In this article, we evaluated the safety of IOCS during radical nephrectomy with inferior vena cava thrombectomy under cardiopulmonary bypass with or without deep hypothermic circulatory arrest. Design and method: In this retrospective comparative multicenter analysis, clinical characteristics of 27 consecutive patients who underwent surgery with or without IOCS between 2012 and 2022 in three referral care units were collected into a database. The need for an allogenic blood transfusion (ABT) was also recorded, defined as any transfusion that occurred either intraoperatively or during the hospital stay. Results: The need for ABT in the cell saver arm was significantly smaller due to the reinfusion of rescued blood (p < 0.015). In multivariate analysis, no cell saver usage was an independent predictor for complications ⩾3 Clavien 3a [odds ratio (OR) 18.71, 95% CI 1.056-331.703, p = 0.046]. No usage of IOCS was an independent predictor for a lower risk of death (OR 0.277, 95% CI 0.062-0.825, p = 0.024). During follow-up, patients who received salvaged blood did not experience an increased risk for developing local recurrence or distant metastases. Conclusion: Transfusion of autologous blood is safe and can be using during nephrectomy and thrombectomy for advanced RCC.

Role of intraoperative cell salvage techniques in the management of renal tumors with advanced caval extension En bloc removal of the kidney with tumor thrombus excision in a multidisciplinary team remains the standard treatment for RCC with tumor thrombus extension. Intraoperative cell salvage techniques (IOCS) can decrease the need for allogeneic blood and prevent blood transfusion related complications. In this article we demonstrated that transfusion of autologous blood is safe and can be using during nephrectomy and thrombectomy for advanced renal cell carcinoma.

Triple therapy in metastatic hormone-sensitive prostate cancer.

PURPOSE OF REVIEW: Over the last years, there have been striking changes in the management of metastatic hormone-sensitive prostate cancer (mHSPC) based on survival advantage of combining either a new hormonal agent (NHA) or docetaxel (D) with androgen deprivation therapy (ADT). Some of these studies primarily assessing doublet treatment included men who underwent concomitant or sequential treatment with D. Most recently, prospective randomized evidence emerged on this triplet strategy too. We aimed to outline the current data and ongoing trials evaluating the usage of the triplet therapy in male individuals with mHSPC. RECENT FINDINGS: Phase III trials PEACE-1 and ARASENS showed that the upfront triplet treatment with ADT+D and either abiraterone acetate or darolutamide outperformed ADT+D in terms of survival, while severe toxicity was mainly driven by D. Importantly, prospective evidence comparing triplet vs. ADT+NHA is still lacking. SUMMARY: Men with de novo high-volume disease benefit most from the triplet, while in cases with metachronous and/or low-volume disease, survival advantage is still disputable. As efficacy of ADT+NHA does not appear to be substantially amplified by combination with D, those men with a more favorable underlying tumor biology might mostly benefit from this doublet, also taking quality-adjusted survival into account.

Focal therapy for primary tumor and metastases in de novo or recurrent oligometastatic prostate cancer: current standing and future perspectives.

PURPOSE: Focal therapy (FT) is gaining increasing acceptance in the management of localized prostate cancer particularly due to its favorable safety. Preliminary evidence suggests advantageous utilization of local treatment in the field of oligometastatic prostate cancer (OMPC). Since data on the utilization of FT in OMPC are scarce, we sought to summarize available evidence. METHODS: For this narrative comprehensive review, we employed PubMed®, Web of Science™, Embase®, Scopus®, and clinicaltrial.gov databases and Google web search engine to seek peer-reviewed articles, published abstracts from international congresses, and ongoing trials in the English language using the terms "prostate cancer", "oligometastatic", "hormone-sensitive", "focal therapy", "focal treatment", "cryotherapy", "ablation", "cancer" as well as "metastasis-directed therapy. We focused on relevant publications on FT utilized in OMPC targeting the primary or metastatic sites as well as completed and ongoing clinical trials. RESULTS: Growing evidence points to distinct differences in the biologic behavior and molecular signaling processes of OMPC as compared to polymetastatic disease (PMPC). No established biomarkers are available to accurately identify OMPC yet, while several candidates are currently under investigation. The evolution of molecular imaging is set to aid in selecting patients benefitting most from local management. Differences between OMPC and PMPC should be considered when designing the optimal therapeutic strategy. While efficacy data for FT in comparison to standard care in OMPC are scarce, longer progression-free survival and time to castration resistance have been demonstrated for bone metastatic prostate cancer with the primary tumor treated by cryosurgery followed by androgen deprivation therapy (ADT) compared to ADT alone. CONCLUSION: Ongoing research efforts are eagerly awaited to better characterize OMPC and establish customized strategies for patients with this condition.

Challenges in Diagnosis of Uretero-Arterial Fistulas after Complex Pelvic Oncological Procedures-Single Center Experience and Review of the Literature.

Introduction: Uretero-arterial fistula (UAF) represents a rare condition that manifests as massive or intermittent hematuria and requires collaboration between a urologist, vascular surgeon and interventional radiologist. In this article, we present our experience with UAF diagnosis, treatment pathways and the results of a nonsystematic review of the literature published in the last decade regarding modern diagnostic procedures. Material and method: We analyzed the clinical data of nine consecutive patients from our institution diagnosed with UAF in the interval of 2012-2022 who underwent open or endovascular surgical treatment. We reviewed patient characteristics, diagnoses and treatment pathways. The literature search resulted in 14 case series, published from 2012 to 2022, describing a total of 670 cases of UAF. Results: The mean age of patients in our cohort was 65.3 years (IQR: 51-79). UAFs were more common in women (77.7%). All patients presented a history of surgical intervention and ir-radiation for pelvic malignancy with permanent ureteric stenting. Overall, 88.8% of patients had urinary diversion, either via ileal conduit or cutaneous ureterostomy. The most common clinical manifestation of UAF was gross hematuria with or without clots accompanied by flank pain due to stent obstruction, while three patients presented with hypovolemic shock. Angiography represents the best option for diagnosis, followed by angioCT, with a sensitivity of 59.83% and 47.01%, respectively. There is no definitive imaging modality associated with high accuracy in detecting UAF and negative findings do not exclude the disease. In emergency cases with massive bleeding, surgical exploration remains the most appropriate management option for both diagnosis and treatment. Endovascular stent graft placement is preferred over open surgery in stable hemodynamic patients. Conclusions: Uretero-arterial fistulas represent a life-threatening complication and must be treated with great awareness. Angiography represents the best modality for diagnosis, followed by computed tomography. However, there is no definitive imaging modality and, in some cases, open approach remains the only option for diagnosis and treatment.

Molecular Mechanisms Related with Oligometastatic Prostate Cancer-Is It Just a Matter of Numbers?

During the last decade, the body of knowledge regarding the oligometastatic state has increased exponentially. Several molecular frameworks have been established, aiding our understanding of metastatic spread caused by genetically unstable cells that adapt to a tissue environment which is distant from the primary tumor. In the current narrative review, we provide an overview of the current treatment landscape of oligometastatic cancer, focusing on the current biomarkers used in the identification of true oligometastatic disease and highlighting the impact of molecular imaging on stage shift in different scenarios. Finally, we address current and future directions regarding the use of genetic and epigenetic targeting treatments in oligometastatic prostate cancer.

Multicentric comparative analysis of Retzius versus Retzius sparing robotic assisted simple prostatectomy in the management of large prostate glands.

AIM: Robot-assisted simple prostatectomy (RASP) is a minimally invasive alternative to open simple prostatectomy in the management of patients with large prostate glands suffering from moderate-to-severe lower urinary tract symptoms (LUTS). Our study aimed to evaluate two transvesical robotic approaches in order to compare functional outcomes and postoperative complications. MATERIALS AND METHODS: Clinical data from 111 consecutive patients from three tertiary robotic centers were retrospectively collected. Patients were divided into two groups depending on the surgical approach: 58 Retzius sparing and 53 Retzius approach RASP. We evaluated peri-operative outcomes (operating time, blood loss, transfusion rate, length of hospital stay), as well as intra-operative and early complications using a Clavien Dindo scale. Fisher's exact test, chi-square test and Mann-Whitney U test were applied for statistical analyses. A p-value <0.05 was considered statistically significant. RESULTS: Neither subgroup differed significantly in age (p = 0.104), Charlson comorbidity index (p = 0.088) or prostate volume (p = 0.507), total IPSS score (0.763) and Qmax (p = 0.651). Total complication rates were lower for the Retzius approach subgroup (19 vs 11.9%) without reaching statistical significance in multivariate analysis (HR = 1.21, 95% CI = 0.17 - 8.44, p = 0.84). No significant differences based on IPSS total score and Qmax could be observed between the two subgroups during follow-up. CONCLUSIONS: Both RASP approaches provide similar results in terms of functional outcomes and present a good safety profile in the management of large prostatic adenomas. Larger trials are needed in order to establish the indications for each robotic technique.

Neuroendocrine syndrome in bronchial carcinoid tumors.

Pulmonary carcinoid tumors represent bronchopulmonary neuroendocrine neoplasms which might synthetize serotonin, histamine, bombesin or other types of hormones responsible for the development of a broad spectrum of signs and symptoms, known as carcinoid syndrome. Data of 98 patients submitted to surgery for bronchial carcinoid tumors in the Thoracic Surgery Clinic of the 'Marius Nasta' Institute of Pneumophtisiology between 2014 and 2018 were retrospectively reviewed. All patients were submitted to paraclinical tests, imagistic studies (computed tomography or magnetic resonance imaging), bronchoscopy and biopsy in order to have a positive diagnostic of pulmonary carcinoid. The most common clinical symptoms at the time of presentation were: Persistent cough followed by dyspnea and recurrent pulmonary infections. The main neuroendocrine syndromes found were Cushing and Carcinoid Syndrome. All patients were submitted to surgery with curative intent consisting of wedge resection (in 4 cases, 4.08%), lobectomy (in 79 cases, 80.61%), bilobectomy (in 5 cases, 5.1%) and pneumonectomy respectively (in 10 cases, 10.2%). In all cases neuroendocrine specific symptoms disappeared once the carcinoid tumor was removed. In conclusion, bronchial carcinoid tumors have a positive outcome in most cases. Specific neuroendocrine markers as well as neuroendocrine syndrome disappears once the tumor is removed.

External validation of a postoperative nomogram for the prediction of disease-specific survival in patients with papillary renal cell carcinoma using a large multicenter database.

PURPOSE: Based on data retrieved from a comprehensive multicenter database, we externally validated a published postoperative nomogram for the prediction of disease-specific survival (DSS) in patients with papillary renal cell carcinoma (papRCC). METHODS: A multicenter database containing data of 2325 patients with surgically treated papRCC was used as validation cohort. After exclusion of patients with missing data and patients included in the development cohort, 1372 patients were included in the final analysis. DSS-probabilities according to the nomogram were calculated and compared to actual DSS-probabilities. Subsequently, calibration plots and decision curve analyses were applied. RESULTS: The median follow-up was 38 months (IQR 11.8-80.7). Median DSS was not reached. The c-index of the nomogram was 0.71 (95% CI 0.60-0.83). A sensitivity analysis including only patients operated after 1998 delivered a c-index of 0.84 (95% CI 0.77-0.92). Calibration plots showed slight underestimation of nomogram-predicted DSS in probability ranges below 90%: median nomogram-predicted 5-year DSS in the range below 90% was 55% (IQR 20-80), but the median actual 5-year DSS in the same group was 58% (95% CI 52-65). Decision-curve analysis showed a positive net-benefit for probability ranges between a DSS probability of 5% and 85%. CONCLUSIONS: The nomogram performance was satisfactory for almost all DSS probabilities; hence it can be recommended for application in clinical routine and for counseling of patients with papRCC.

Surgical management of urachal tumors: Can the umbilicus be sparred in localized disease?

Urachal adenocarcinoma represents the third most common histological type of non-urotelial bladder cancer. A very low incidence of this disease and the lack of prospective studies have led to a rich and heterogeneous treatment history. Currently, the standard of care for these patients is represented by partial cystectomy en bloc with resection of the urachal ligament and total omphalectomy. The aim of this article is to present our experience and results in the management of patients with urachal adenocarcinoma. Between 2005 and 2015, 16 patients have undergone surgical treatment for urachal adenocarcinoma in "Fundeni" Clinical Institute and Madrid University Hospital "Infanta Sofia." Partial cystectomy was performed in 11 (68.76%) patients, while radical cystectomy en bloc with omphalectomy was performed in 5 (31.25%) patients, which were not amendable to a limited resection. The Sheldon classification was used, as it provides appropriate disease staging and is the most commonly utilized. Postoperative pathological results showed that 7 (43.75%) patients had localized tumors, and more than one-third (37.5%) of the patients had locally advanced Sheldon III disease, while 3 patients had distant metastasis at the time of surgery. Lymph node involvement was present in 3 patients (18.75%). Mean follow-up time was 2.5 years, ranging from 4 months to 7.6 years. Three patients (18.75%) were lost to follow-up, without any documented signs of local or systemic recurrence and were cancer free at the time of the last evaluation. In cases with lymph node involvement, local recurrence or distant metastasis, patients underwent cisplatin- or 5-fluorouracil-based salvage chemotherapy. Surgical treatment represents the gold standard, while adjuvant chemotherapy has a limited impact on overall survival. The utility of navel resection is questionable due to the rarity of direct invasion or local recurrence.

Aggressive variants of prostate cancer - Are we ready to apply specific treatment right now?

Recently, adoption of novel drugs for systemic treatment of metastatic prostate cancer has led to a striking improvement of response rate and survival in both hormone-sensitive and castration-resistant disease. In most cases, prostate cancer essentially depends on androgen receptor signaling axis, even in castration-resistant setting, and hence may be targeted by second generation hormonal therapy. However, a subset of patients bears androgen-independent cancer biology with a short-term response to hormonal treatment, early and extensive visceral metastases, low PSA levels and poor outcomes. Identification and specific management of these rapidly fatal malignancies is of an unmet medical need since their classification and utilized therapeutic regimens vary significantly. Unfortunately, molecular pathways have not been sufficiently elucidated yet in order to provide an effective targeted treatment with a prolonged response. Lack of diagnostic and predictive biomarkers for these cancers makes successful counteractions against them even more sophisticated. In this comprehensive review, we aimed at summarizing the current body of literature reporting on causal molecular machinery as well as diagnostic and therapeutic concepts of aggressive prostate tumors and draw clinically relevant conclusions for the up-to-date sensible disease management.

Combining anticancer drugs with osteoprotective agents in prostate cancer-A contemporary update.

Recently, a plethora of life-prolonging cytotoxic, next-generation hormonal, immunotherapeutical as well as radionuclide therapies has emerged as a standard care for metastasized castration-resistant prostate cancer. Being strikingly effective in cancer control, these novel therapies might in fact exert a beneficial impact on skeletal events. Therefore, combining anticancer drugs with osteoprotective agents might lead to additional clinical advantage but must be weighed against simultaneously exposing patients to serious toxicities. In addition, further survival prolongation by changing treatment paradigm in both metastasized hormone-sensitive and nonmetastatic castration-resistant disease might potentially increase the risk for bone density reduction complications due to a growing efficacy of androgen ablation leading to prolonged exposure. To address both possible indications of combined treatment and to draw practical conclusions, we performed a comprehensive review of the currently available evidence.

Prognostic and discriminative power of the 7th TNM classification for patients with surgically treated papillary renal cell carcinoma: results of a multi-institutional validation study (CORONA subtype project).

OBJECTIVE: Studies on the prognostic reliability of the Union for International Cancer Control tumor, node, metastasis (TNM) staging system for renal cell carcinoma (RCC) predominantly focus on clear-cell RCC. Therefore, the aim of this study was to investigate whether the oncological prognosis of surgically treated papillary RCC (papRCC) patients is reliably given by the current TNM system, by analyzing the largest database reported to date. MATERIALS AND METHODS: Data on 2325 papRCC patients who underwent surgical treatment in 1984- 2015 were collated from 17 international centers (median follow-up 47 months). Tumor stage was adapted to the 7th edition of the TNM system. Multivariable, bootstrap-corrected Cox regression models were applied to assess the independent impact of the TNM system on cancer-specific mortality (CSM) and all-cause mortality (ACM). RESULTS: The median age at diagnosis was 63 years (interquartile range 54-70 years) and 77% of patients were male. Nephron-sparing surgery was performed in 42%, and 82% were with symptom free at diagnosis. In 6.7% (n = 156), organ metastasis (stage M1) was present at the time of surgery. On multivariable analysis, the TNM system and Fuhrman grade had an independent impact on both CSM and ACM, while patient age affected ACM only. The discriminative ability of the pT classification was significant for both endpoints: 5 year CSM rates were 5%, 17%, 36% and 56% for stages pT1, pT2, pT3 and pT4, respectively (each p < 0.001). The pT classification contributed significantly to the predictive accuracy of the CSM and ACM models by 6.3% and 2.5%, respectively (each p < 0.001). CONCLUSIONS: The 2010 TNM staging system can be reliably applied to papRCC patients and allows certain prognostic discrimination.

Medical management in locally advanced and metastatic prostate cancer: Does changes in treatment policy have any specific effect on PSA levels?

OBJECTIVE: Androgen deprivation therapy (ADT) is commonly used as a first-line treatment for locally advanced and metastatic prostatic cancer (Pca). There is no consensus about which alternative treatment should be used after the failure of initial ADT. We aimed to investigate the effect of changes in treatment on PSA and testosterone levels. MATERIAL AND METHODS: A total of 120 patients with an established diagnosis of either locally advanced or metastatic Pca in two different centers. Depending on the type of medical and/or surgical management protocol planned at initial presentation, all cases were divided into three main groups as follows. Group 1 (n: 80) included the patients who underwent medical management during whole follow-up period in whom the initial management protocol was later on switched to another medical treatment with different agents, Group 2 (n: 20) included patients who were initially treated with a medical management protocol and switched to surgical castration during follow-up evaluation and lastly Group 3 (n: 20) included the patients undergoing treated surgical castration as initial treatment modality without any further medical management protocol. RESULTS: Evaluation of our data did clearly demonstrate a statistically significant difference between the initial and final PSA as well as testosterone levels in Group 1 cases. Mean PSA and testosterone levels increased significantly in these cases despite a change in hormonal therapy by using another agent for androgen deprivation. Cases in Group 2 and 3 cases did not show any statistically significant difference with respect to the mean PSA as well as testosterone values during the same follow-up period. CONCLUSIONS: Our data clearly indicated that in case of a biochemical progression, switching into another alternative medical treatment was not effective enough in limiting the rising PSA levels in a statistically significant manner when compared with the approaches of switching to surgical castration after initial medical treatment or continuing with regular and close follow-up after initial surgical castration alone.

Can we expand active surveillance criteria to include biopsy Gleason 3+4 prostate cancer? A multi-institutional study of 2,323 patients.

OBJECTIVE: To test the expandability of active surveillance (AS) to Gleason score 3+4 cancers by assessing the unfavorable disease risk in a large multi-institutional cohort. MATERIALS AND METHODS: We performed a retrospective analysis including 2,323 patients with localized Gleason score 3+4 prostate cancer who underwent a radical prostatectomy between 2005 and 2013 from 6 academic centers. We analyzed the rates of biopsy downgrading/upgrading and advanced stage in the overall cohort by employing standardized AS criteria (using biopsy Gleason score 3+4). RESULTS: The final pathologic Gleason score was 3+3 = 6 in 8%, 3+4 = 7 in 67%, 4+3 = 7 in 20%, and 8 to 10 in 5% cases. The overall rate of unfavorable disease (upgrading or advanced stage or both) was 46%. In multivariable analysis, prostate-specific antigen (PSA) level>10 ng/ml, PSA density (PSAD) >0.15 ng/ml/g, clinical stage >T1, and>2 positive cores were predictors of unfavorable disease. According to the AS criteria used, the risk of unfavorable disease ranged from 30% to 42%. In patients without any risk factor (PSA level≤ 10 ng/ml, PSAD ≤ 0.15 ng/ml/g, T1c, and ≤ 2 positive cores), the unfavorable disease rate was 19%. The main limitations of this study are the retrospective design and nonstandardization of pathologic assessment between centers. CONCLUSIONS: Approximately half of patients with biopsy Gleason score 3+4 cancer have unfavorable disease at final pathology. Nevertheless, expanding AS eligibility to these patients may be acceptable provided adherence to strict selection criteria leading to a<20% risk of unfavorable disease. Future tools for selection such as magnetic resonance imaging, early rebiopsy, and serum markers may be especially beneficial in this group of patients.