Real-world prostate-specific antigen reduction and survival outcomes of metastatic hormone-sensitive prostate cancer patients treated with apalutamide: An observational, retrospective, and multicentre study.

Background: Metastatic hormone-sensitive prostate cancer (mHSPC) treatment has changed drastically during the last years with the emergence of androgen receptor-targeted agents (ARTAs). ARTA combined with androgen deprivation therapy has demonstrated better oncological and survival outcomes in these patients. However, the optimal choice among different ARTAs remains uncertain due to their analogous efficacy. Objectives: The objective of this study was to describe prostate-specific antigen (PSA) response and oncological outcomes of patients with mHSPC treated with apalutamide. Material and methods: Medical records from three different hospitals in Spain were used to conduct this study. Patients diagnosed with mHSPC and under apalutamide treatment were included between March 2021 and January 2023. Data regarding PSA response, overall survival (OS), and radiographic progression-free survival (rPFS) were collected and stratified by metastasis volume, timing, and stating. Results: 193 patients were included; 34.2% of patients were de novo mHSPC, and the majority was classified as m1b. The 18-month OS and rPFS were 92.5% and 88.9%, respectively. Patients with PSA levels ≤0.2 ng/ml showcased an 18-month OS rate of 98.7%, contrasting with 65.3% for those with PSA >0.2 ng/ml. Similar trends emerged for rPFS (97.4% and 53.7%, respectively). When differentiating between low-volume and high-volume metastasis, the OS rate stood at 98.4% and 80.7%, respectively, while the rPFS rates were 93% and 81.6%, respectively. No significant differences were found between groups stratified by metastasis timing. Conclusion: This real-world study on patients with mHSPC treated with apalutamide plus androgen deprivation therapy revealed robust oncological outcomes, aligning with the emerging evidence. The study's hallmark finding highlights the significance of rapid and deep PSA response as a predictor of improved oncological and survival outcomes.

Manual Therapy Intervention in Men With Chronic Pelvic Pain Syndrome or Chronic Prostatitis: An Exploratory Prospective Case-Series.

Purpose Chronic pelvic pain syndrome (CPPS) is permanent pelvic pain of unknown etiology. Current theories suggest a multifactorial origin for CPPS, including urinary pathologies, psychosocial factors, prostate inflammation, infection, central sensitization of the nervous system, and muscular contractures or fibrosis. As there are no defined treatment protocols for CPPS, a multimodal approach is recommended. The objective of this study was to evaluate the impact of a manual therapy treatment protocol on pain, urinary symptoms, and overall quality of life. Materials and Methods Twenty-three men aged 47.36 ± 10.11 years were recruited consecutively by urologists practicing at two hospitals. All men presented prostatic tenderness with no other positive clinical history, urine cultures, or echography studies. Patients underwent six manual therapy sessions (three during the first week and three every two weeks after that) performed by a single osteopath or physiotherapist. The intervention protocol addressed the treatment of muscle structures, fascial mechanics, vascularization, innervation, emotional factors, and the need for information. The questionnaires used to evaluate outcomes included the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI), the International Prostate Symptoms Score (IPSS), and a Visual Analog Scale (VAS) for pain, and the Hospital Anxiety and Depression Scale (HADS). Data were evaluated using Chi-squared or paired difference tests by an external researcher. Results The mean NIH-CPSI scores recorded for our study cohort decreased by 7.69 points (30.92%; p<0.0005; 95% CI 4.02-10.52). IPSS measurements decreased by 3.20 points (22.18%; p=0.009; 95% CI 1.00-6.09), although the item addressing quality of life decreased by 1.67 points only (31.99%; p<0.0005; 95% CI 0.94-2.33). The VAS score also decreased by 2.20 points (38.6%; p<0.0005; 95% CI 1.45-2.73). Changes in HADS scores were not statistically significant. Conclusions Based on patient responses, this case series revealed that manual therapy improved urinary symptoms, pain, and quality of life.

Simultaneous pancreas-kidney transplantation: Early complications and long-term outcomes - a single-center experience.

INTRODUCTION: This study aimed to assess the prevalence and severity of complications after simultaneous pancreas-kidney transplantation (SPKT) and to evaluate its influence on both grafts' long-term results. METHODS: This was an observational, retrospective study including 39 consecutive SPKT cases from 2000-2018. Complications were classified into kidney-related and pancreas-related. The severity of complications was assessed using the modified Clavien-Dindo scale. Kaplan-Meier curve analysis and log-rank tests were used. Cox regression was performed for the multivariate analysis. RESULTS: All 39 recipients had long-term type I diabetes. Twenty-one (53.8%) patients suffered a Clavien-Dindo ≥IIIa complication. Most complications were pancreas-related, with 17 (43.6%) patients suffering from one. Kidney-related major complications were seen in 11 (28.2%) patients. Patient survival at one, five, and 15 years was 89.7%, 87.1%, and 83.9%, respectively; kidney survival was 87.1%, 81.4%, and 73.6%, respectively; and pancreas survival was 76.9%, 71.3%, and 72%, respectively. Pancreas graft survival was influenced by the presence of major postoperative complications; patients and kidney graft survival were not. CONCLUSIONS: Complications after SPKT influence pancreas graft survival. Despite the high rate of complications, our results suggest that patient and kidney graft survival may not be affected by complications.

CD8+ T lymphocytes are sensitive to NKG2A/HLA-E licensing interaction: role in the survival of cancer patients.

NK and CD8+ T cells are the main cytolytic effectors involved in innate and adaptive tumor immune surveillance, respectively. Although their educational pathways differ, similarities in their development and function suggest that CD8+ T lymphocytes could be sensitive to NK cell licensing signals, which might influence their antitumor response. To demonstrate this hypothesis, we retrospectively evaluated the impact that NK cell licensing interactions have on the expression of CD226 on CD8+ T lymphocytes and on the survival of patients with different hematopoietic and solid cancers (n = 1,023). Prospectively, we analyzed by multiparametric flow cytometry the anti-CD3/CD28-induced proliferation and immune-receptor expression of purified CD8+ T lymphocytes from healthy donors (n = 17) with different combinations of NK cell licensing ligands. Results show that methionine/threonine (M/T) dimorphism at position -21 of the HLA-B leader peptide, but not other HLA class-I dimorphisms involved in the education of NK cells (HLA-C1/C2 or HLA-Bw4), is associated with greater survival and expression of CD226 in cancer patients, which was proportional to the number of methionines present in their genotype. CD8+ T lymphocytes from healthy donors with -21 M showed higher proliferation rates and lower expression of TIGIT after in vitro stimulation. Therefore, CD8+ T lymphocytes, like NK cells, appear to be sensitive to the -21 M/T dimorphism of HLA-B leader peptide, which results in the modulation of CD226 in vivo and the proliferation and expression of TIGIT after in vitro stimulation, all of which could be related to their immune-surveillance capacity and the survival of cancer patients.

Immunological Risk Stratification of Bladder Cancer Based on Peripheral Blood Natural Killer Cell Biomarkers.

BACKGROUND: Bladder cancer (BC) is highly immunogenic. Bacillus Calmette-Guérin (BCG) immunotherapy offers the best results in non-muscle-invasive BC (NMIBC). Natural killer cells (NKcs) play decisive roles in BCG-mediated immune response and in general cancer immune-surveillance. OBJECTIVE: To analyze killer-cell immunoglobulin-like receptors (KIRs), their human leukocyte antigen class-I (HLA-I) ligands, and the expression of DNAX Accessory Molecule-1 (DNAM-1/CD226) on peripheral blood (PB) NKcs, to identify useful predictive biomarkers in BC. DESIGN, SETTING, AND PARTICIPANTS: KIR/HLA-ligand genotypes were compared between 132 BC, 201 other solid cancers, 164 plasma cell disorders, and 615 healthy Caucasoid controls. CD226 expression was evaluated by flow cytometry. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: KIR/HLA-I interactions and CD226 expression on NKcs (CD226high or CD226low) were compared across study groups, cancer stages, treatments, and progression-free and overall survival of patients, using chi-square, analysis of variance/post hoc, Kaplan-Meier/log-rank, and regression analyses. RESULTS AND LIMITATIONS: Three immunological risk groups were identified: low risk (KIR2DL1-L2+L3-/C1C1- and KIR2DL1+L2+L3+/C1C1+), intermediate risk (rest), and high risk (KIR2DL5+/HLA-C*16+ and KIR2DL1+L2+L3-), which displayed different 10-yr progression-free rates (83.3%, 48.6%, and 0%, respectively; p<0.001) and survival rates (83.3%, 54.3%, and 6.2%, respectively; p<0.001) for muscle-invasive T2/T4, and 10-yr progression-free rates (100%, 81.6%, and 50%, respectively; p<0.05) for NMIBC-T1 treated with BCG. Immunological risk stratification had an independent prognostic value to just histological staging for survival (hazard ratio=2.93, p<0.00001, Harrell C-statistic=0.779). CD226 expression on PB NKcs improved immunological stratification in intermediate-risk T1-T4 BC patients, with survival rates of 94.1% and 66.7% for CD226high and CD226low (p<0.05), respectively. CONCLUSIONS: Immunological risk stratification will complement BC histopathology to improve risk stratification and guide the selection of personalized treatments. Understanding of the molecular mechanisms of NKc tumor immune surveillance will enable the development of future NKc-based therapies. PATIENT SUMMARY: This work describes a peripheral blood test that aids in our understanding of the immune defense mechanisms against bladder cancer, is useful for classifying patient risk, and will guide personalized treatments.

KIR+ CD8+ T Lymphocytes in Cancer Immunosurveillance and Patient Survival: Gene Expression Profiling.

Killer-cell immunoglobulin-like receptors (KIR) are expressed by natural killer (NK) and effector T cells. Although KIR+ T cells accumulate in oncologic patients, their role in cancer immune response remains elusive. This study explored the role of KIR+CD8+ T cells in cancer immunosurveillance by analyzing their frequency at diagnosis in the blood of 249 patients (80 melanomas, 80 bladder cancers, and 89 ovarian cancers), their relationship with overall survival (OS) of patients, and their gene expression profiles. KIR2DL1+ CD8+ T cells expanded in the presence of HLA-C2-ligands in patients who survived, but it did not in patients who died. In contrast, presence of HLA-C1-ligands was associated with dose-dependent expansions of KIR2DL2/S2+ CD8+ T cells and with shorter OS. KIR interactions with their specific ligands profoundly impacted CD8+ T cell expression profiles, involving multiple signaling pathways, effector functions, the secretome, and consequently, the cellular microenvironment, which could impact their cancer immunosurveillance capacities. KIR2DL1/S1+ CD8+ T cells showed a gene expression signature related to efficient tumor immunosurveillance, whereas KIR2DL2/L3/S2+CD8+ T cells showed transcriptomic profiles related to suppressive anti-tumor responses. These results could be the basis for the discovery of new therapeutic targets so that the outcome of patients with cancer can be improved.

Benign renal schwannoma: Case report and literature review.

Renal schwannoma is a very infrequent tumor. It is usually benign and it does not have any specific symptoms or imaging characteristics. Its final diagnosis is usually made after surgery. We present a 66 year-old-man that was referred to our center after the casual finding of a renal mass. With a suspected diagnosis of a renal cell carcinoma, a partial nephrectomy was performed. The histological study revealed the final diagnosis of a benign renal schwannoma.

Bacillus Calmette-Guérin in Immunosuppressed Patient with High-Grade Nonmuscle Invasive Bladder Carcinoma.

Due to their immunosuppressed status, solid organ transplant recipients are a special group of patients with an incidence of bladder cancer greater than the rest of the population, especially in the first 6 years after transplantation. Also, treatment with Bacillus Calmette-Guérin, a reference therapy in nonmuscle invasive high-risk bladder cancer, may be less effective in this group of patients and could cause more adverse effects. However, the data published so far and the experience initiated in the Virgen de la Arrixaca Clinical University Hospital do not support these hypotheses.

Conservative management is a reasonable option in intraperitoneal bladder rupture.

OBJECTIVE: To demonstrate that conservative management of intraperitoneal bladder rupture is a safe option. METHOD: We report two cases of intraperitoneal bladder rupture, one spontaneous and another after urological manipulation. A 28-year-old man with acute abdomen after a heavy alcohol intake, and an 83-year-old woman with abdominal distention after a transurethral resection of the bladder. RESULT: Both cases were treated with intraperitoneal fluid evacuation and maintenance of urinary catheter without incidents. CONCLUSIONS: Conservative management with drainage of ascites in combination with a radiological studies and optimal antibiotic treatment can prevent more invasive maneuvers such as exploratory laparotomy or laparoscopy.

Must we still be worried about multiple arteries in kidney transplantation?

BACKGROUND: Multiple renal arteries in kidney grafts have been associated with an increased rate of vascular and urologic complications. Our objective is to compare the outcome of transplanted patients who receive a single pedicle kidney with those who receive a multiple arterial graft. OBJECTIVES: To find our the differences in the outcome and complications in patients undergoing kidney transplantation with one single artery or with multiple arteries. PATIENTS AND METHODS: We analyzed 147 kidney transplantations, (all performed in our hospital over a 3 year period). population divided into two groups: group A for those who presented with only one renal artery, or group B for those with more than one renal artery. Homogeneous vascular reconstructions and implantation rules were applied in all patients. We compared the rates of renal failure between the two groups, urinary and vascular complications, patient and graft survivals and the levels of creatinine clearance during the first year of post-transplantation. RESULTS: No significant differences were found between the two groups regarding to the values analyzed. CONCLUSIONS: As many other authors, we do believe that the presence of multiple renal arteries in kidney grafts should not be considered as a predictive factor of transplantation failure.

Hematuria secondary to congenital arteriovenous fistula treated with embolization.

OBJECTIVE: To report a rare case of hematuria caused by an arteriovenous fistula which may be a urological emergency. METHODS: We describe the medical history, physical examination, complementary tests performed and their results, as well as the treatment applied in an adolescent with hematuria. RESULTS: Congenital arteriovenous fistula was diagnosed and treated by percutaneous embolization with immediate stop of hematuria. CONCLUSION: Non-traumatic renal arteriovenous fistulae are rare, even more if they present with gross hematuria. We present a case of a life-threatening emergency caused by one of them the treatment of which was possible by embolization, avoiding surgery.

Retrocaval ureter in children. Case report and bibliographic review.

OBJECTIVE: Retrocaval ureter is a rare disease which is due to a abnormal development of the inferior cava vein. It usually presents with ureteral obstruction, and surgery is needed for symptomatic cases. METHOD: We present a case of retrocaval ureter and a revision of the literature. RESULTS: A 9 year-old boy who had consulted for macroscopic hematuria. The intravenous urography (IVU) suggested the diagnosis of retrocaval right ureter, which is confirmed by magnetic resonance imaging (MR). Make us resection of the retrocaval segment and relocation of the ureter anterior to the inferior vena cava. Follow-up IVU showed good resolution of hydronephrosis. CONCLUSIONS: Retrocaval ureter is a rare disease, with easy diagnostic and effective treatment. Other associated anomalies could be associated.

[Hand-assisted laparoscopic nephroureterectomy for the treatment of upper urinary tract transitional cancer]. / Nefroureterectomía laparoscópica mediante laparoscopia asistida por la mano para el tratamiento del carcinoma transicional del tracto urinario superior.

OBJECTIVE: To report our series of patients undergoing hand-assisted laparoscopic nephroureterectomy (HALNU) using the pluck-off procedure. MATERIALS AND METHODS: Twenty patient undergoing HALMU for upper urinary tract urothelial tumors from November 2002 to December 2007 were assessed. Demographic, clinical, surgical, and oncological data were assessed. RESULTS: Mean patient age was 69 years. Mean operating time and mean intraoperative bleeding were 176 min and 381 mL respectively. Twenty percent of patients required transfusion of blood products. Conversion to open surgery was not required in any patient. Major and minor complications occurred in 25% and 30% of patients respectively.Mean time to oral intake was 48 hours, and mean hospital stay was 5 days.Pathological study revealed transitional cell carcinoma in all cases: grade I in 5%, grade II in 60%, and grade III in 35% of patients. Clinical stage was pTa in 5%, pT1 in 20%, pT2 in 25%, pT3 in 40%, and pT4 in 10% of patients. A bladder recurrence rate of 30% and a 49% overall survival were seen after a mean follow-up of 33 months (5-73). Six-year cancer-specific survival was 67%. No patient developed either peritoneal or surgical bed recurrence. CONCLUSIONS: HALMU using the pluck-off procedure is a feasible, safe, and effective surgery. Both surgical and oncological results are similar to those of open surgery and pure laparoscopy.

[Hand-assisted laparoscopic radical nephrectomy vs. open nephrectomy in the treatment of clinically localized renal cell carcinoma. Comparative study]. / Nefrectomía radical laparoscópica asistida por la mano frente a nefrectomía abierta en el tratamiento del carcinoma de células renales clínicamente localizado. Estudio comparativo.

INTRODUCTION: The description of the first laparoscopic nephrectomy made a revolution in the managing of the benign and malignant renal diseases. Hand-assisted laparoscopy (HAL) was developed with the aim of offering advantages to both patients and surgeons. The aim of the present work is to compare, in our experience, the results offered in the radical nephrectomy by HAL and open surgery, by analysis of surgical time, estimated blood loss during surgery and hospital stay. METHODS: Eleven Hand-assisted laparoscopic (HAL) radical nephrectomies and eight open radical nephrectomies were carried out at our institution during the same period (June 2001 to December 2002). All patients underwent computed tomography and were found to have a clinically localised functioning renal mass in all cases. The size of this renal mass was 4-7 cm (average 5.5 cm) in the HAL group and 4.5-15 cm (average 7.8 cm) in the open group. Patient age, body mass index, and American Society of Anaesthesiologists' score showed no significant difference between groups. RESULTS: The average surgical time in the HAL group was 156.72 minutes, the average blood loss during surgery was of 83.6 ml and the average hospital stay was of 3.09 days. Conversion to open surgery was not necessary in any patient. Average surgical time in the open surgery group was 178.25 minutes, the estimated blood loss during surgery was of 337.75 ml (p < 0.05) and the hospital stay was of 5.37 days (p < 0.05). The comparison of the means by two-tailed student's t test revealed significant differences in estimated blood loss and hospital stay, favoring HAL, and no significant differences in surgical time. CONCLUSIONS: HAL nephrectomy is feasible in almost all nephrectomies and is a safe, reproducible, and minimally invasive technique to perform extirpable renal surgery. HAL offer clear advantages over traditional open surgery, including decreased blood loss and hospital stay.

[Fatal evolution of a renal angiosarcoma]. / Evolución fatal de angiosarcoma renal.

OBJECTIVES: Report a new case of renal angiosarcoma treated by surgery and adjuvant chemotherapy with bad results. METHODS: 72-year-old male undergoing right nephrectomy for renal tumor. Pathology reports renal angiosarcoma. RESULTS: Three months after surgery patient refers lumbar pain and hemoptysis and CT scan reveals the existence of multiple bone and lung metastasis; a regimen of systemic chemotherapy with Doxorrubicine+ Ifosfamide was started without response; he died two months later. CONCLUSIONS: Primary renal angiosarcoma is very rare, with less than 10 cases in the literature before 1998, and it is always associated with bad prognosis. Diagnosis is based on immunohistochemical studies (antibodies against CD31, CD34 and factor VIII related antigen) to define the endothelial differentiation of the tumor. There is no experience to define the best therapeutic strategy against this entity.

[Relation between hypertension and clinical cases of benign prostatic hyperplasia]. / Estudio de la relación entre hipertensión y caso clínico de hiperplasia benigna de próstata.

OBJECTIVES: To confirm the relationship between hypertension and lower urinary tract symptoms (LUTS) in our environment, and to evaluate the association between hypertension and LUTS secondary to benign prostatic hypertrophy (BPH). METHODS: We prospectively studied during 3 months all male patients older than 50 years (163 patients) analysing previous medical history, IPSS, digital rectal examination, urine sediment, basic biochemical profile, PSA, uroflowmetry, and urinary tract ultrasound. Patients with neurological diseases, previous pelvic trauma, diabetes mellitus, suspicious digital rectal examination, abnormal PSA, or under treatment with alpha blockers, antidepressants, finasteride or antipsychotic drugs were excluded. RESULTS: From a total of 163 patients 113 were classified as suffering clinical BPH (LUTS, prostate greater than 30 gm, and uroflowmetry < 15 ml/sec), and 75 as hypertensive. Among 75 hypertensive patients 31 presented IPSS greater than 7 (41.3%) in comparison to 20 out of 88 non hypertensive patients (22.7%), being the difference statistically significant. CONCLUSIONS: Our study confirms what has been previously reported by other authors, that there is a statistically significant relationship between hypertension and LUTS secondary to BPH.

[Magnetic resonance urogram as alternative to i.v. urography. Report of 3 cases. Review of the literature]. / Urograma en resonancia magnética como alternativa a la urografia i.v. A propósito de tres casos. Revisión de la literatura.

OBJECTIVES: Intravenous urography (IVU) has been classically considered as an essential examination in the great majority of urologic diseases due to the great amount of information that supplies both functional and morphological, mainly for ureteral abnormalities where other exams do not reach enough definition. Nevertheless, there are cases in which it is not possible to perform an intravenous urography due to allergy to iodine contrasts or renal failure with impossibility of contrast excretion. METHODS: We report three cases which represent the example of the indications of MRI urography as an alternative to IVU in cases in which this latter cannot or should not be performed. RESULTS: MRI urography is completely accepted as a diagnostic technique for urologic diseases as an alternative to IVU. It has advantages, such as obtaining images in multiple planes, avoiding the use of ionizing radiation, that there is no evidence of it causing cell damage, that it does not require glomerular elimination of any substance so it can be used in patients with renal failure and allergy to iodine contrasts. CONCLUSIONS: The use of MRI urography results in an advantage for patients with renal failure, iodine contrasts allergy, or greater risk of contrast nephrotoxicity as it is the case of renal transplant patients.

[Controversies in the evaluation of asymptomatic microhematuria]. / Controversias en la evaluación de la microhematuria asintomática.

OBJECTIVE: Asymptomatic microhematuria continues to be a problem. It has a prevalence of 16% and numerous conditions can present this clinical manifestation. METHODS: A prospective study was carried out on all patients that consulted at the urological services during 2000 for asymptomatic hematuria. Patients presenting with irritative symptoms, urethral secretion, perineal or suprapubic pain, urinary tract infections, renal lithiasis or history of trauma were not included in the study. RESULTS: None of the patients presented tumors. Two patients presented renal lithiasis, 5 simple renal cysts, 8 hypercalciuria and 3 hyperuricosuria. None of the 11 patients with hypercalciuria or hyperuricosuria had a history of lithiasis. CONCLUSIONS: Although the size of the study is small, the incidence of tumors in patients with asymptomatic microhematuria appears to be far from the 12.5% incidence reported by some authors and might probably be closer to the 0.5% incidence reported by others. Furthermore, the significant pathology (renal lithiasis), which requires treatment, is also infrequent.