Prevalence and management of urinary incontinece after pelvic organ prolapse surgery (sacrocolpopexy). A literature review.

INTRODUCTION: Stress urinary incontinence (SUI) is frequently associated with pelvic organ prolapse (POP) and may occur after its surgical treatment. AIM: To determine the incidence, risk factors and management of SUI during and after POP surgery through a review of the available literature. MATERIALS AND METHOD: Narrative literature review on the incidence and management of SUI after POP surgery after search of relevant manuscripts indexed in PubMed, EMBASE and Scielo published in Spanish and English between 2013 and 2023. RESULTS: Occult SUI is defined as visible urine leakage when prolapse is reduced in patients without SUI symptoms. De novo SUI develops after prolapse surgery without having previously existed. In continent patients, the number needed to treat (NNT) to prevent one case of de novo SUI is estimated to be 9 patients and about 17 to avoid repeat incontinence surgery. In patients with occult UI, the NNT to avoid repeat incontinence surgery is around 7. Patients with POP and concomitant SUI are the group most likely to benefit from combined surgery with a more favorable NNT (NNT 2). CONCLUSION: Quality studies on combined surgery for treatment SUI and POP repair are lacking. Continent patients with prolapse should be warned of the risk of de novo SUI, although concomitant incontinence treatment is not currently recommended. Incontinence surgery should be considered on an individual basis in patients with prolapse and SUI.

Peritoneal carcinomatosis after partial nephrectomy for renal cell carcinoma: Our experience and literature review.

OBJECTIVE: Peritoneal carcinomatosis associated with renal cell carcinoma is an infrequent entity, usually associated with large renal masses, and with a very rare presentation after surgery of localized renal tumors. Our objective is to review the literature and analyze the factors involved in the development of peritoneal carcinomatosis after laparoscopic partial nephrectomy in localized tumors. MATERIAL AND METHODS: We present our experience with two cases of peritoneal carcinomatosis after laparoscopic partial nephrectomy. We reviewed the literature and analyzed the factors associated with the development of peritoneal carcinomatosis after laparoscopic partial surgery in renal cell carcinoma. RESULTS: Between 2005-2018, 225 patients underwent laparoscopic partial nephrectomy for localized renal neoplasia in our service. Two patients developed peritoneal carcinomatosis during follow-up, at 1.5 and 7 years after surgery. Few cases of postoperative peritoneal carcinomatosis for renal neoplasia have been described in the literature, being more frequently associated with large renal masses, with multiple metastases at diagnosis, with a poor prognosis. The dissemination of tumor cells during surgery, direct tumor extension or metastasis by hematogenous route, are among the factors involved in the development of this condition. CONCLUSIONS: Peritoneal carcinomatosis after laparoscopic partial nephrectomy constitutes a very rare event. However, it should be taken into consideration, and, since it is the only factor we can influence, we must maximize precautions during the surgical act, following oncological principles.

Laparoscopic nephron sparing surgery and radical nephrectomy in cT1 renal tumors. Comparative analysis of complications and survival.

INTRODUCTION AND OBJECTIVES: Comparative analysis of postoperative complications and survival between laparoscopic partial nephrectomy (PN) and radical nephrectomy (RN) in cT1 renal cell carcinoma (RCC). MATERIAL AND METHOD: Retrospective study of patients with two kidneys and single renal tumor cT1 treated in our center between 2005 and 2018 by laparoscopic PN or RN. RESULTS: 372 patients met the inclusion criteria for the study. RN was performed in 156 (41.9%) patients and PN in 216 (58.1%). Clavien Dindo III-V complications were observed in 10 (4,6%) PN and 6 (3,9%) RN patients (p = 0.75). The comorbidity Charlson index (CCI) was identified as an independent predictor variable of complications (p = 0.02) and surgical approach did not affect multivariate analysis. Estimated overall survival (OS) was 81.2% and 56.8% at 5 and 10 years in the RN group and 90.2% and 75.7% in the PN group, respectively (p = 0.0001). Obesity (HR 2.77, p = 0.01), CCI ≥ 3 (HR 3.69, p = 0.001) and glomerular filtration rate (GFR) <60 mL/min/1.73 m2 at discharge (HR 1.87, p = 0.03) were identified as predictors of overall mortality. Nephrectomy approach showed no influence on OS. Estimated recurrence-free survival (RFS) was 86.1% at 5 and 10 years in the RN group and 93.5% and 83.6% in the PN group, respectively (p = 0.22). CONCLUSIONS: Laparoscopic PN is not inferior to RN in terms of oncologic and surgical safety in cT1 RCC. Nephrectomy approach did not influence patient OS, however, obesity, CCI ≥ 3 and GFR <60 mL/min/1.73 m2 at discharge did behave as predictors.

Mortality prediction model for patients with bladder urothelial tumor after radical cystectomy. / Modelo predictivo de mortalidad en pacientes con tumor urotelial de vejiga tras cistectomía radical.

OBJECTIVE: Based on preoperative clinical and postoperative pathological variables, we aim to build a prediction model of cancer specific mortality (CSM) at 1, 3, and 5 years for patients with bladder transitional cell carcinoma treated with RC. MATERIAL AND METHODS: Retrospective analysis of 517 patients with diagnosis of cell carcinoma treated by RC (1986-2009). Demographic, clinical, surgical and pathological variables were collected, as well as complications and evolution after RC. Comparative analysis included Chi square test and ANOVA technique. Survival analysis was performed using Kaplan-Meier method and log-rank test. Univariate and multivariate analyses were performed using logistic regression to identify the independent predictors of CSM. The individual probability of CSM was calculated at 1, 3 and 5 years according to the general equation (logistic function). Calibration was obtained by the Hosmer-Lemeshow method and discrimination with the elaboration of a ROC curve (area under the curve). RESULTS: BC was the cause of death in 225 patients (45%). One, three and five-year CSM were 17%, 39.2% and 46.3%, respectively. The pT and pN stages were identified as independent prognostic variables of CSM at 1, 3 and 5 years. Three prediction models were built. The predictive capacity was 70.8% (CI 95% 65-77%, p=.000) for the 1st year, 73.9% (CI95% 69.2-78.6%, p=.000) for the third and 73.2% (CI% 68.5-77.9%, p=.000) for the 5th. CONCLUSIONS: The prediction model allows the estimation of CSM risk at 1, 3 and 5 years, with a reliability of 70.8, 73.9 and 73.2%, respectively.

Recurrence risk groups after nephrectomy for renal cell carcinoma. / Clasificación en grupos de riesgo de recurrencia tras nefrectomía por cáncer renal.

INTRODUCTION: There is no consensus on the follow-up protocol after nephrectomy for renal cell carcinoma (RCC), and the identification of recurrence risk groups (RRG) is required. OBJECTIVE: Establish recurrence risk groups (RRG). MATERIAL AND METHOD: A retrospective analysis of 696 patients with renal cancer submitted to surgery between 1990-2010; 568 (81.6%) patients treated with radical nephrectomy and 128 (18.4%) treated with partial nephrectomy. Pathological variables were classified as: 1st-level variables (1LPV): pTpN stage and Fuhrman grade (FG); and 2nd level pathological variables (2LPV): sarcomatoid differentiation (SD), tumor necrosis (TN), microvascular invasion (MVI) and positive surgical margins (PSM). Univariate and multivariate analysis have been performed using Cox regression to determine 1LPV related to recurrence. Based on 1LPV, we classified patients into three RRG: Low (LRG)<25%; Intermediate (IRG) 26-50% and High (HRG)>50%. We performed univariate and multivariate analysis with the 2LPVs for each RRG. With these data, patients were reclassified as RRG+. ROC curves were used for comparison of RRG and RRG+. RESULTS: The median follow-up was 105 months (range 63 to 148). There were 177 (25.4%) patients with recurrence: 111 (15.9%) distant, 34 (4.9%) local and 32 (4.6%) distant and local. In the multivariable analysis, Fuhrman grade (HR=2,75; P=.0001) and pTpN stage (HR=2,19; P=.0001) behaved as independent predictive variables of recurrence. Patients were grouped as RRG (AUC=0,76; p=0,0001): - LRG (pT1pNx-0 G1-4; pT2pNx-0 G1-2): 456 (65,5%) patients. - IRG (pT2pNx-0 G3-4; pT3-4pNx-0 G1-2): 110 (15,8%) patients. - HRG (pT3-4pNx-0 G3-4; pT1-4pN+): 130 (18,6%) patients. After multivariate analysis with 2LPV, RRG were reclassified (RRG+) (AUC=.84, P=.0001): -LRG+(LRG without TN, SD and/or PSM(+)). -IRG+(IRG; LRG with TN) -HRG+(HRG; LRG with SD and/or PSM(+); IRG with TN and/or SD) CONCLUSIONS: The inclusion of 2LPV to the classification according to VP1N improves the discriminating capacity of RRG classification.

Evaluation of laparoscopic approach in radical cystectomy from implementation to consolidation: Internal validation. / Evaluación del abordaje laparoscópico en la cistectomía radical desde la implantación hasta su consolidación: validación interna.

INTRODUCTION AND OBJECTIVES: The AEU Guidelines of 2017 consider laparoscopic and robot-assisted approaches as investigational procedures. The surgical learning curve is defined as the minimum number of cases that a surgeon has to perform in order to reproduce a technique considered as standard. The aim of this study is to analyze, within our department, the implementation of a laparoscopic radical cystectomy (LRC) program compared with a well consolidated and standardized open radical cystectomy (ORC) program. MATERIAL AND METHODS: Retrospective cohort analysis of two cystectomy groups: LRC (n=196) (20062016) vs. ORC (n=96) (2003-2005). Comparison of the evolution over time of the following parameters: operative time, blood transfusion rates, resection margins, postoperative complications, hospital stay and recurrence. Three time periods have been defined for LRC: implementation (2006-09) (LRC-I), development (2010-14) (LRC-D) and consolidation (2015-16) (LRC-C); comparing each of them with the control group (ORC). The chi-square test was used for the comparison of the qualitative variables and the Anova test for the numerical ones. RESULTS: When compared to ORC, LRC presented longer operative times in LRC-I and LRC-D periods. We observed a trend toward shorter operative time than ORC in the consolidation period (LRC-C). LRC also presented lower intraoperative transfusion rates in all periods and lower postoperative rates in CRL-D and CRL-C. Overall complications in LRC-D and LRC-C were lower in LRC, having fewer major complications (Clavien≥3) in the 3 periods. A decrease in mortality and hospital stay after the LRC-I phase was also observed. These results were consolidated during the two last periods of the study. We have not observed significant differences between ORC and LRC when comparing surgical margins and recurrence rates, neither in the total series, nor in the comparison between the different periods. These results endorse the oncologic safety of LRC from the beginning of the implementation process. CONCLUSIONS: When compared to ORC, LRC improves perioperative transfusion rates, complications and hospital stay from its implementation period, maintaining oncological safety. On the contrary, longer operative times during implementation and development were observed. However, in our series, we observed a trend toward shorter operative times than ORC approach in the consolidation period. We have validated the laparoscopic approach for radical cystectomy in our service.

Effect of adjuvant chemotherapy in locally advanced urothelial carcinoma of the bladder treated with cystectomy. / Efecto de la quimioterapia adyuvante en el carcinoma urotelial de vejiga localmente avanzado tratado con cistectomía.

INTRODUCTION: Currently, the role of adjuvant chemotherapy (ADJ) in muscle invasive bladder tumor remains controversial. OBJECTIVE: To evaluate the effect of ADJ on cancer specific survival of muscle invasive bladder tumor after radical cystectomy (RC). MATERIAL AND METHODS: Retrospective analysis of 292 patients diagnosed with urothelial bladder tumor pT3-4pN0 / + cM0 stage, treated with RC between 1986-2009. Total cohort was divided in two groups: 185 (63.4%) patients treated with ADJ and 107 (36.6%) without ADJ. Median follow-up was 40.5 months (IQR 55-80.5). Comparative analysis was performed with Chi-square test and Student's t test /ANOVA. Survival analysis was carried out with the Kaplan-Meier method and log-rank test. Multivariate analysis (Cox regression) was made to identify independent predictors of cancer-specific mortality (CSM). RESULTS: 42.8% of the series presented lymph node involvement after RC. At the end of follow-up, 22.9% were BC-free and 54.8% had died due to this cause. The median cancer specific survival was 30 months. No significant differences were observed in cancer specific survival regarding the treatment with ADJ in pT3pN0 (p=.25) or pT4pN0 (p=.29) patients, but it was significant in pT3-4pN+ (p=.001). Multivariate analysis showed pathological stage (p=.0001) and treatment with ADJ (p=.007) as independent prognostic factors for CSM. ADJ reduced the risk of CSM (HR:0.59,95% CI 0.40-0.87, p=.007). CONCLUSIONS: pT and pN stages were identified as independent predictors of CSM after RC. The administration of ADJ in our series behaved as a protective factor reducing the risk of CSM, although only pN+ patients were benefited in the stage analysis.

Post-surgical complications in patients with bladder cancer treated with cystectomy: Differences between open and laparoscopic approach. / Complicaciones posquirúrgicas en los pacientes con cáncer de vejiga tratados con cistectomía: Diferencias entre el abordaje abierto y laparoscópico.

INTRODUCTION: Minimally invasive surgery regarding cystectomy has not had the same development as other urological surgeries. This could be due to the lack of published studies defining the advantages of this approach versus open surgery. OBJECTIVES: The main objective of this study is to establish the role of minimally invasive surgery, laparoscopic radical cystectomy, versus open surgery by analyzing their perioperative complications. MATERIAL AND METHOD: Retrospective cohort analysis of perioperative complications of 2homogeneous series of cystectomies: laparoscopic (n = 196) versus open (n = 197). Identification of independent predictors of perioperative complications by multivariate analysis. RESULTS: In the comparative analysis between laparoscopic cystectomies and open cystectomies we observed a lower rate of perioperative blood transfusion (P < 0.0001), a lower rate of global postoperative complications (P < 0.0001) and a lower rate of serious complications (Clavien > 3; P < 0.001) in the LRC group. There was also a lower mortality rate in the laparoscopic series compared to open ones (P < 0.0001). Surgical approach and surgical time (P < 0.001) were identified as independent predictors of complications. CONCLUSIONS: We have identified the laparoscopic approach as a complication shield for radical cystectomy. The open approach almost triples the risk of complications.

Influence of laparoscopic access in cancer-specific mortality of patients with pTa-2pN0R0 bladder cancer treated with radical cistectomy. / Influencia del acceso laparoscópico en la mortalidad cáncer-específica de los pacientes con cáncer de vejiga en un estadio pTa-2pN0R0 tratados con cistectomía radical.

INTRODUCTION AND OBJECTIVE: Minimally invasive surgery represents an attractive surgical approach in radical cystectomy. However, its effect on the oncological results is still controversial due to the lack of definite analyses. The objective of this study is to evaluate the effect of the laparoscopic approach on cancer-specific mortality. MATERIAL AND METHOD: A retrospective cohort study of two groups of patients in a pT0-2pN0R0 stage, undergoing open radical cystectomy (ORC) (n=191) and laparoscopic radical cystectomy (LRC) (n=74). Using Cox regression, an analysis has been carried out to identify the predictor variables in the first place, and consequently, the independent predictor variables related to survival. RESULTS: 90.9% were males with a median age of 65years and a median follow-up period of 65.5 (IQR27.75-122) months. Patients with laparoscopic access presented a significantly higher ASA index (P=.0001), a longer time between TUR and cystectomy (P=.04), a lower rate of intraoperative transfusion (P=.0001), a lower pT stage (P=.002) and a lower incidence of infection associated with surgical wounds (P=.04). When analyzing the different risk factors associated with cancer-specific mortality, we only found the ORC approach (versus LRC) as an independent predictor of cancer-specific mortality (P=.007). Open approach to cystectomy multiplied the risk of mortality by 3.27. CONCLUSIONS: In our series, the laparoscopic approach does not represent a risk factor compared to the open approach in pT0-2N0R0 patients.

Influence of the laparoscopic approach on cancer-specific mortality of patients with stage pt3-4 bladder cancer treated with cystectomy. / Influencia del acceso laparoscópico en la mortalidad cáncer específica de los pacientes con cáncer de vejiga en un estadio pT3-4 tratados con cistectomía.

INTRODUCTION AND AIM: The main aim of the study was to establish the oncological safety of the laparoscopic approach to radical cystectomy for high-risk, non-organ-confined urothelial tumours. MATERIAL AND METHODS: A retrospective cohort study of 216 stage pT3-4 cystectomies operated between 2003 and 2016; using an open approach (ORC, n=108), and using a laparoscopic approach (LRC, n=108). RESULTS: Both groups have similar pathological features except, in G3 TUR, there were more lyphadenectomies and greater pN+, and more adjuvant chemotherapies using the LRC. The median follow-up of the series was 15 (IQR: 8-10.5) months. Sixty-eight point one percent of the series relapsed, with no differences between either group (p=.11). The estimated differences for cancer-specific survival was greater in the LRC group (p=.03), as was overall survival (p=.009). There were no differences between either group in estimated recurrence-free survival (p=.26). The type of surgical approach (p=.03), pTpN stage (p=.0001), and administration of adjuvant chemotherapy (p=.003) were related to cancer-specific mortality (CSM) in the univariate analysis. Only the pTpN stage (p=.0001), and not giving adjuvant chemotherapy (p=.003) behaved as independent predictive factors of CSM. CONCLUSION: The type of surgical approach to cystectomy (ORC vs. LRC) did not influence CSM. Lymph node involvement and not giving adjuvant chemotherapy were identified as predictive factors of CSM. Our study supports the oncological safety of the laparascopic approach for cystectomy in patients with locally advanced muscle-invasive bladder tumours.

The need for re-TUR of the bladder in non-muscle invasive bladder cancer: risk factors of tumor persistence in re-TUR specimens.

AIM: This study evaluated the need for re-TUR of the bladder in non-muscle invasive bladder cancer (NMIBC) with complete transurethral resection (TUR) and examined the risk factors for disease occurrence in re-TUR of the bladder. METHODS: A cohort of 211 patients diagnosed consecutively of NMIBC (July 2009 to October 2011) underwent re-TURB 4-6 weeks after the initial TURB. Association with tumor presence in re-TURB of the following parameters was analyzed: sex, primary/recurrent, number, size, stage, grade, association of carcinoma in situ, early instillation of Mitomycin C, and its classification according to the EORTC risk groups. RESULTS: Fifty-seven (27%) cases exhibited residual tumors in the re-TURB and understaging was observed in 3 (1.4%) patients. The EORTC classified 151 (71.6%) patients as high risk; 124 (58.7%) patients received postoperative instillations of Mitomycin C. 31.8% of high risk patients exhibited tumors in the re-TUR compared to 14% of the low/intermediate risk (P<0.05). A total of 19.4% of patients with early instillation of Mitomycin C had tumor in re-TURB compared to 38.4% of patients without it (P<0.05). Multivariate analysis showed that high-risk tumors behaved as an independent risk factor for the tumor presence in re-TURB (HR=12.65, P=0.008), but early postoperative instillation of Mitomycin C was a protective factor (HR=2.16, P=0.02). The limitations of the study are the absence of randomization and its unicentric character. CONCLUSION: Patients who were at a high risk of tumor recurrence and/or progression according to the EORTC classification exhibited a higher percentage of tumors in re-TURB. Therefore, these patients are optimal candidates for re-TURB.

Bladder cancer in Spain 2011: population based study.

PURPOSE: We estimate the annual incidence of bladder cancer in Spain and describe the clinical profile of patients with bladder cancer enrolled in a population based study. MATERIALS AND METHODS: Using the structure of the Spanish National Health System as a basis, in 2011 the AEU (Spanish Association of Urology) conducted this study with a representative sample from 26 public hospitals and a reference population of 10,146,534 inhabitants, comprising 21.5% of the Spanish population. RESULTS: A total of 4,285 episodes of bladder cancer were diagnosed, of which 2,476 (57.8%) were new cases and 1,809 (42.2%) were cases of recurrence, representing an estimated 11,539 new diagnoses annually in Spain. The incidence of bladder cancer in Spain, age adjusted to the standard European population, was 20.08 cases per 100,000 inhabitants (95% CI 13.9, 26.3). Of patients diagnosed with a first episode of bladder cancer 84.3% were male, generally older than 59 years (81.7%) with a mean ± SD age of 70.5 ± 11.4 years. Of these patients 87.5% presented with some type of clinical symptom, with macroscopic hematuria (90.8%) being the most commonly detected. The majority of primary tumors were nonmuscle invasive (76.7%) but included a high proportion of high grade tumors (43.7%). According to the ISUP (International Society of Urologic Pathology)/WHO (2004) classification 51.1% was papillary high grade carcinoma. Carcinoma in situ was found in 2.2% of primary and 5.8% of recurrent cases. CONCLUSIONS: The incidence of bladder cancer in Spain, age adjusted to the standard European population, confirms that Spain has one of the highest incidences in Europe. Most primary nonmuscle invasive bladder cancer corresponded to high risk patients but with a low detected incidence of carcinoma in situ.

Fluorescent cisplatin analogues and cytotoxic activity.

Cisplatin is one of the chemotherapeutic agents used the most for testicular, ovarian and several other cancers. In order to overcome cisplatin resistance, other platinum (Pt) compounds have been developed and, in the last ten years, Pt-derivatives with reporting activity have also been synthesized. The first generation of reporting Pt-compounds was based on linking a fluorescent molecule (e.g. cyanine) to cisplatin, but more recent studies have focused on strategies to synthesize intrinsically fluorescent derivatives. Accordingly, bile acid Pt-compounds have shown fluorescence intensity that is stable at room temperature for a long time; this fluorescence is maintained after binding to oligonucleotides or DNA. Because of this, the binding mode of these compounds to DNA can be easily analyzed both by flow injection and fluorescence techniques, showing that although these compounds target the nuclei, they form adducts with the DNA that are different from those due to cisplatin. In line with this, these bile acid derivatives have shown increased cytotoxicity and ability to overcome resistance as compared to cisplatin in several cell lines. Moreover, in contrast to cisplatin, the activity of these compounds does not seem to be restricted to cycling cells but they also seem to kill resting cells. This review summarizes the information available on reporting Pt-compounds and focuses on these novel, intrinsically fluorescent bile acid Pt derivatives, their biochemical characteristics and biological activity.

[TVA and TOA. New adjustable mesh for the treatment of female stress incontinence. Preliminaries results]. / TVA y TOA. Nuevas mallas ajustables de tensión en el tratamiento de la incontinencia urinaria de esfuerzo. Resultados preliminares.

OBJECTIVES: Evaluation of a new mesh for incontinence (TVA/TOA) which enables the degree of tension applied during surgery to be readjusted at the post-operative stage. PATIENTS AND METHOD: 62 patients treated with the TVA mesh and monitored over a 14-month period (SD 7.8, range 6-38). In 33 patients (53%) some other pelvic prolapse was corrected. Evaluation was carried out by clinical report, examination of bladder full of 250 saline solution, flowmetry and urinary residue. 40 patients filled in 4 quality of life questionnaires (QoL; ICIQ-SF; PGI-S; PGI-I). RESULTS: 42 patients were found to be objectively continent in the post-operative evaluation. Of these, it was necessary to reduce tension in 7 cases (11%) due to urinary obstruction (flow < 10 ml/sec and/or residue). The tension of the mesh was tightened in 20 patients (32%) due to continue with a certain degree of incontinence. All patients were discharged as continent and with no residue. In the last revision, 58 patients (93%) proved to be objectively continent and 4 (6.5%) showed a notable improvement in their incontinence. The Q(MAX) is 19.8 ml/sec (SD 9.8). The mictional urgency had disappeared or improved in 32 of the patients who had this prior to operation (76%) and had appeared in 3 of the patients who didn't (15%). The clinical report showed a high level of consensus with the ICIQ-SF survey (Kappa = 0.89) regarding stress incontinence, diminishing clearly (Kappa= 0.13) when urge incontinence was taken into account. 34 (85%) patients scored over 95 out of 110 in the QoL. 30 (75%) scored less than 6 in ICIQ-SF. 32 (80%) showed a perception of normality and 4 (10%) slight illness in the PGI-S. In the PGI-I 29 (72.5%) were much better and 11 (27.5%) quite a lot better. A relation exists between urgency and dismissed quality of life. CONCLUSION: With the TVA (trans-vaginal adjustable) mesh it is possible to adjust the tension originally applied during surgery at the post-operative stage, so that any defects or excesses can be corrected.

New organotropic compounds. Synthesis, characterization and reactivity of Pt(II) and Au(III) complexes with bile acids: DNA interactions and 'in vitro' anticancer activity.

Based on the ability of bile acids to vectorialize the cytostatic activity of other agents, we have designed and synthesized a new series of platinum and gold complexes. These compounds were studied and characterized by elemental analysis, FT-IR, FAB(+)/MS, 1H, 13C and 195Pt NMR, UV-Vis spectroscopy and conductivity measurements in solution, among other techniques. Kinetic studies carried out in aqueous solution and in the presence of different NaCl concentrations: 4 mM (similar to cytoplasmic concentration), 150 mM (similar to plasmatic concentration). The effects on the electrophoretic mobility of the pUC18 plasmid, the DNA denaturation temperature, and ethidium bromide (EtBr) binding to DNA were studied. The complexes are able to inter-react with DNA to inhibit DNA synthesis and hence, to reduce cell proliferation. The complexes were evaluated for in vitro cytostatic activity against human colon adenocarcinoma, mouse hepatoma, human hepatoma, mouse leukemia, etc. The antitumor effect of some of the compounds prepared was similar to that of cisplatin. However, other compounds had lower cytostatic activity. This different behavior can be accounted for by the structure/activity relationship (SAR), although other factors, such as uptake and the different kinetic behavior in solution, may be responsible for these differences.

Thiourea derivatives and their nickel(II) and platinum(II) complexes: antifungal activity.

We have synthesized two thiourea derivatives of methyl anthranilate (1, 2) and their complexes with nickel (3) and platinum(II) (4). We have also prepared the complexes of nickel(II) with two benzoylthiourea derivatives (5, 6). The obtained compounds were characterized by elemental analysis, spectroscopic methods (FT-IR, UV-vis, NMR), mass spectrometry and thermal analysis. Compound 1, C(20)H(23)N(3)O(2)S, crystallizes in monoclinic space group P21/n, with Z=4, and unit cell parameters, a=8.8042(4) A, b=7.6608(3) A, c=28.834(2) A, alpha=gamma=90 degrees, beta=90.94(1) degrees. Compound 2, C(20)H(21)N(3)O(3)S, crystallizes in monoclinic space group P21/c, with Z=4, and unit cell parameters, a=7.7345(4) A, b=8.6715(4) A, c=29.113(2) A, alpha=gamma=90 degrees, beta=90.67(1) degrees. Compound 5, C(24)H(30)N(4)NiO(2)S(2), crystallizes in monoclinic space group P21/n, with Z=4, and unit cell parameters, a=10.4317(8) A, b=18.517(2) A, c=13.299(1) A, alpha=gamma=90 degrees, beta=104.53(1) degrees. Compound 6, C(25)H(28)Cl(2)N(4)NiO(4)S(2), crystallizes with a molecule of CH(2)Cl(2) in triclinic space group P-1, with Z=2, and unit cell parameters, a=10.362(1) A, b=11.849(2) A, c=12.536(2) A, alpha=90.04(2) degrees, beta=84.73(1) degrees, gamma=113.43(2) degrees. Compounds 1 and 2 show antifungal activity against the major pathogens responsible for important plant diseases (Botrytis cinerea, Colletotrichum fragariae, Fusarium oxysporum and Phoma betae). The antifungal activity is practically the same for morpholine and ethyl derivatives.

Synthesis and characterization of sodium cis-dichlorochenodeoxycholylglycinato(O,N) platinum(II)--cytostatic activity.

With a view to using bile acids as shuttles for delivering platinum-related cytostatic drugs to liver tumors, a chenodeoxycholylglycinato(CDCG)-derivative of platinum(II) has been synthesized. The complex--named Bamet-M2--was chemically characterized by elemental analysis, FT-IR, NMR, FAB-MS, and UV spectroscopy. The results indicate the following composition: C26H42N2O5Cl2NaPt(II), the metal Pt(II) being bound to two Cl- and one bidentate CDCG moiety, i.e., Na[Pt CDCG(N,O) Cl2]. The compound is highly soluble (up to 20 mM) in water and (up to 35 mM) in ethanol, methanol and DMSO. Hydrolysis was investigated because this is assumed to be an important step in intracellular activation and interaction with DNA of this type of compounds. The reaction kinetics of this complex in aqueous solution show unusual behaviour; the substitution process with the displacement of two Cl- was almost instantaneous, and the resulting species were found to be very stable. Kinetic studies carried out in the presence of different NaCl concentrations (up to 500 mM) revealed similar fast and nonreversible aquations of Bamet-M2. This contrasts with the slow aquation of cisplatin in extracellular-line solutions (i.e., at high NaCl concentrations) as compared with fast hydrolysis in cells. This difference may partly account for the low cytostatic activity observed here for Bamet-M2 against several tumor cell-lines.

[Effectiveness of transrectal ultrasonography in local staging of prostatic cancer]. / Eficacia de la ecografía transrectal en el estadiaje local del cáncer de próstata.

OBJECT: To evaluate the value of rectal examination, transrectal ultrasound and their association in patients with prostate cancer undergoing radical prostatectomy. MATERIAL AND METHODS: Retrospective study on 56 patients who underwent radical prostatectomy between 1995-1995, mean age 63.2 +/- 10 years, to compare local clinical staging of extracapsular dissemination and seminal vesicle invasion performed by rectal examination and transrectal ultrasound with pathological findings in the prostatectomy specimens. The sensitivity, specificity, VPP, VPN, accuracy and percentage of under- and over-staged patients were assessed. RESULTS: Prevalence of locally advanced disease was 48%. Sensitivity to detect extracapsular dissemination was significantly higher with ultrasound (38%) than rectal examination (6%). Association of both techniques increased the sensitivity (50%) though not significantly; sensitivity to detect vesicle invasion was very low (14%). Accuracy of ultrasound to establish an overall definition of the local stage was 66%, but 59% patients with locally advanced disease were understaged and only 10% patients with localized disease were overstaged. CONCLUSIONS: Transrectal ultrasound showed low sensitivity to define the locally advanced disease mainly at the seminal vesicle level, with acceptable specificity. Overall evaluation of findings with RE and TRU increase discreetly the efficacy of prostate capsule staging.

[Yield of ultrasound-guided transrectal biopsy in the diagnosis of prostatic cancer in symptomatic patients]. / Rendimiento de la biopsia transrectal ecodirigida en el diagnóstico del cáncer de próstata en los pacientes sintomáticos.

OBJECTIVE: The aim of this retrospective study was to evaluate the utility of US-guided transrectal biopsy of the prostate in the diagnosis of prostatic cancer in symptomatic patients and its correlation with the digital rectal examination (DRE), PSA levels and ultrasound findings. METHODS: From 1994 to 1995, 427 patients with prostatic symptomatology underwent prostatic biopsy. The mean age was 69.1 +/- 8.3 years (range 44 - 89). The criteria for biopsy were abnormal DRE, PSA > 10 ng/ml, abnormal US findings and/or PSA density > 0.15. RESULTS: Prostate cancer was confirmed in 42% of the patients. The incidence of cancer when DRE was abnormal was 73%, 46% when PSA was > 10 ng/ml and 55% when the US findings were abnormal; 82% for abnormal DRE and PSA > 10 ng/ml, and 84% when the criterion of abnormal US was included. The incidence of cancer when DRE was normal was 16%, 18% when combined with PSA > 10 ng/ml and remained unchanged when combined with the US findings. In patients with normal DRE and PSA between 10 - 30 ng/ml, the incidence of cancer was 14% and 41% for those with PSA > 30 ng/ml. CONCLUSION: DRE was the best independent predictor of prostate cancer and the combination of abnormal DRE, PSA > 10 ng/ml and abnormal US findings gave the highest detection rate. The incidence of prostate cancer was very low in patients with normal DRE and PSA between 10 - 30 ng/ml, which may be due to the fact that the PSA levels are raised by the non neoplastic changes in the transitional zone in symptomatic patients.

[Correlation of prostatic specific antigen, tumor grade, and local stage with bone scintigraphy in the staging of patients with prostatic cancer]. / Correlación entre el antígeno específico prostático, el grado tumoral y el estadio local con la gammagrafía ósea en el estadadiaje de los pacientes con cáncer de próstata.

OBJECTIVE: To determine the capacity of PSA, tumor grade and local stage to predict the bone scintiscan findings in patients with newly diagnosed, untreated prostate cancer. METHODS: We analyzed the records of 189 patients with prostate cancer that had been seen at our institution from January, 1993 to September, 1995. PSA determination was performed prior to biopsy, local staging by DRE or transrectal US was done and they had a bone scintiscan before treatment. RESULTS: 21% of the patients had metastasis. Univariate analysis showed PSA (p < 0.001), tumor grade (p = 0.01) and local stage (p = 0.001) independently predicted the positive bone scintiscans. However, multivariate regression analysis showed tumor grade (rc = 0.05) or stage (rc = 0.07) did not increase the predictive value of PSA (rc = 0.22). The highest negative predictive value of PSA [95% (IC95 = 87.5%, 98.6%)] was obtained when 20 ng/ml was used as cutoff. Therefore 1.4% to 13.5% of the patients with bone metastasis could not have been diagnosed without scintigraphy. CONCLUSION: Bone scintigraphy should be performed routinely to determine the extent of the lesion in patients with prostatic cancer, particularly in those patients that are likely to undergo radical treatment.