Activating KIRs on Educated NK Cells Support Downregulation of CD226 and Inefficient Tumor Immunosurveillance.

Therapies using NK cells (NKc) expanded/activated ex vivo or stimulated in vivo with new immunostimulatory agents offer alternative opportunities for patients with recurrent/refractory tumors, but relevant biomarkers to guide the selection of patients are required for optimum results. Overall survival of 249 solid cancer patients was evaluated in relation to the genetics and/or the expression on peripheral blood NKcs of inhibitory and activating killer-cell immunoglobulin-like receptors (iKIR and aKIR, respectively), HLA class I ligands, CD226 (also known as DNAM-1), and NKG2A. Compared with patients with higher expression, patients with low expression of CD226 on total NKcs showed shorter mean overall survival (60.7 vs. 98.0 months, P < 0.001), which was further reduced in presence of telomeric aKIRs (KIR2DS1-DS5 and/or KIR3DS1, 31.6 vs. 96.8 months, P < 0.001). KIR2DL2/S2+, KIR3DL1+, KIR2DL1+, and KIR2DL3+ NKc subsets in the presence of their cognate ligands primarily contributed to shortening patients' overall survival by increasing the sensitivity to CD226 downmodulation in aKIR-rich telomeric genotypes. In patients with high tumor burden who died during the follow-up period, aKIR-rich telomeric genotypes were associated with: (i) specific downmodulation of CD226 on educated NKcs but not on CD8+ T cells or uneducated NKcs, (ii) lower expression of CD226 and higher expression of NKG2A on aKIR+ NKcs, and (iii) lower numbers of total CD56dim NKcs. The reduced expression of CD226 on NKcs with aKIR-rich genotypes may be a biomarker indicative of NKc hyporesponsiveness in patients that could benefit from new NKc immune-stimulatory therapies.

NK Cell Education in Tumor Immune Surveillance: DNAM-1/KIR Receptor Ratios as Predictive Biomarkers for Solid Tumor Outcome.

Natural killer cell (NKc)-based therapies offer promising outcomes in patients with tumors, but they could improve with appropriate selection of donors and optimization of methods to expand NKcs in vitro Education through licensing interactions of inhibitory killer cell immunoglobulin-like receptors (iKIR) and NKG2A with their cognate HLA class-I ligands optimizes NKc functional competence. This work has evaluated the role of licensing interactions in NKc differentiation and the survival of cancer patients. We have analyzed KIR and KIR-ligand genes, and the expression of activating (CD16 and DNAM-1/CD226) and inhibitory (NKG2A and iKIRs) receptors on peripheral blood NKcs in 621 healthy controls and 249 solid cancer patients (80 melanoma, 80 bladder, and 89 ovarian). Licensing interactions upregulated the expression of activating CD226, reduced that of iKIR receptors, and shifted the CD226/iKIR receptor ratio on NKc membranes to activating receptors. A high tumor burden decreased CD226 expression, reduced the ratio of CD226/iKIR, and negatively affected patient survival. The progression-free survival (38.1 vs. 67.0 months, P < 0.002) and overall survival (56.3 vs. 99.6 months, P < 0.00001) were significantly shorter in patients with lower expression of CD226 on NKcs. Hence, transformed cells can downmodulate these licensing-driven receptor rearrangements as a specific mechanism to escape NKc immune surveillance. Our results suggest the importance of the CD226/iKIR receptor ratio of NKcs induced by licensing interactions as critical determinants for solid cancer immune surveillance, and may provide predictive biomarkers for patient survival that may also improve the selection of donors for NKc immunotherapy.

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.

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.

[The unpublished book on urologic therapy by Dr. D. Victoriano Molina Garcia (1899-1986)]. / El inédito libro sobre terapéutica urológica del Dr. D. Victoriano Molina Garcia (1899-1986).

OBJECTIVES: To present the unpublished original book on Urological Therapeutics of Dr. Victoriano Molina, a great urologist from Valencia, and to outline his biographical sketch. METHODS: We read his treaty on therapeutics and his publications with detail. To elaborate his biography we obtained information from his descendants and the people who worked with him. RESULTS: When he was locked in the besieged Madrid during the Civil war he dedicated his time to write a the rapeutics manual for personal use, which when finished became an excellent treaty in which all the urological pathology was gathered with various clinical scenarios, establishing the medical treatment with precise indications, enriched with numerous magistral formulas and preparations from the time. Dr Molina trained with Dr de la Peña and worked in Hospital de la Princesa with Drs. Cifuentes, father and son, and he was included by Dr. Jimenez Diaz in the staff of the Medical Research Institute, center in which he completed his professional career. CONCLUSION: The treaty of Urological Therapeutics, written in 1938, represents an excellent unpublished urological text, without comparison in the bibliography due to its contents, a manual which could have became an adequate consultation manual in any urological office. The author, remembered by his goodness, his knowledge and his dedication to Urology, is discovered thanks to this work as one of the relevant personalities of the Spanish Urology.

[The Spanish participation in the Congresses of the International Society of Urology during the 20th century]. / Participación española en los Congresos de la Sociedad Internacional de Urología en el siglo XX.

OBJECTIVES: With the occasion of the Centenary of the Constitution in 1907 of the International Society of Urology, initially named Association, we point at the topics treated and analyze the presence of the Spanish urologists in the foundation act as well as their role and contributions in the meetings during the 20th century. METHODS: We obtained the data from the information in various periodic publications, from the memories of some participant urologists and from the meeting records. RESULTS: We obtained notes from the foundation meeting of the International Association and two congresses, and also from the 25 congresses of the Society. We mainly extract data from the records edited by the meeting secretary, about the assistance of Spanish urologists and their contribution with conferences or communications and also about the relevance they have had holding positions within the organization. CONCLUSIONS: From 1907 the presence of Spanish urologists both in the Association and the International Society of Urology has been a constant. During the first half of the century, a time when our Urology was in a period of consolidation, the people in charge of the main urology departments in big hospitals in our country where the ones that could transmit their experience, with a level and quality comparable with the rest of Europeans. During the second half, once the nations recovered from wars, the scientific activity continued with an increasing Spanish contribution, which extended all over the country with the creation of the net of Social Security hospitals. They had hierarchical urology departments that performed study and analysis of their case series and started clinical and experimental research, significantly increasing the number of Spanish communications, mainly in congresses celebrated in Spanish speaking or European cities. As a consequence of their participation, three of the 25 meetings organized during the 20th century have been held in Spain. The Spanish presence in the directing boards of the society was favoured by the presence of Dr. Salvador Gil Vernet to consecutive periods.

[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.

[Infiltrating bladder carcinoma and adrenal incidentaloma. Report of one case. Bibliographic review]. / Carcinoma vesical infiltrante e incidentaloma suprarrenal. A propósito de un caso. Revisión de la literatura.

OBJECTIVES: We report one case of left adrenal tumor discovered during the study of an infiltrating bladder carcinoma. We discuss the diagnostic and therapeutic implications of the clinical case. METHODS: Surgical procedure was undertaken with radical cystectomy and Bricker's type urinary diversion, plus adenomectomy by anterior approach. RESULTS: The pathologic report showed a myelolipoma. CONCLUSIONS: Most adrenal tumors are benign, mainly if they are small and non-functioning. The protocol of hormonal study should include potassium and catecholamines. Tumors greater than 6 cm and functioning masses are indications for surgery. For oncological patients, surgical approach of the lesion is indicated if there is not evidence of dissemination.

[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.