Epidemiological, clinical, and prognostic analysis of oral squamous cell carcinoma diagnosed and treated in a single hospital in Galicia (Spain): a retrospective study with 5-year follow-up.

BACKGROUND: Oral cancer is a common neoplasm worldwide, mostly corresponding to squamous cell carcinoma (OSCC). Unfortunately, its overall prognosis remains poor, with no improvement in recent decades. In this study, we have analysed the epidemiological, clinical, and prognostic characteristics of OSCC on patients of a specific Spanish region (Galicia), in order to improve its prognosis and apply effective preventive and early diagnosis measures. MATERIAL AND METHODS: We retrospectively analysed 243 cases of OSCC, diagnosed and treated in a single hospital centre in Galicia between 2010 and 2015 (minimum of 5 years of evolution). Overall and specific survival were calculated (Kaplan-Meier) and associated variables were identified (log rank test and Cox regression). RESULTS: The mean age of the patients was 67 years, with the majority being male (69.5%), smokers (45.9%) and alcohol consumers (58.6%), who lived in non-urban areas (79.4%). Cases diagnosed at advanced stages entailed the 48.1% of the sample, and 38.7% of cases relapsed. The 5-year overall and disease-specific survival rates were 39.9% and 46.1%, respectively. Patients who consumed tobacco and alcohol had a worse prognosis. OSCC cases referred to hospital by specialist dentists had a better prognosis, as those who were previously diagnosed with an oral potentially malignant oral disorder (OPMD) or received dental care during OSCC treatment. CONCLUSIONS: In view of these findings, we conclude that OSCC in Galicia (Spain) still has a very poor overall prognosis, which is mainly related to the advanced age of the patients and the late diagnosis. Our study highlights the better survival of OSCC in relation to the referring health professional, the presence of a previous OPMD and the dental care after diagnosis. This demonstrates the importance of dentistry as a health profession involved in the early diagnosis and multidisciplinary management of this malignant neoplasm.

Is unicentric familial papillary thyroid microcarcinoma different from multicentric?

BACKGROUND: Familial papillary thyroid microcarcinoma (FPTMC) appears to be more aggressive than sporadic papillary thyroid microcarcinoma (SPTMC). However, there are authors who indicate that unicentric FPTMC has a similar prognosis to SPTMC. The objective is to analyze whether unicentric FPTMC has a better prognosis than multicentric FPTMC. DESIGN AND METHODS: Type of study: National multicenter longitudinal analytical observational study. STUDY POPULATION: Patients with FPTMC. STUDY GROUPS: Two groups were compared: Group A (unicentric FPTMC) vs. Group B (multicentric FPTMC). STUDY VARIABLES: It is analyzed whether between the groups there are: a) differentiating characteristics; and b) prognostic differences. STATISTICAL ANALYSIS: Cox regression analysis and survival analysis. RESULTS: Ninety-four patients were included, 44% (n = 41) with unicentric FPTMC and 56% (n = 53) with multicentric FPTMC. No differences were observed between the groups according to socio-familial, clinical or histological variables. In the group B a more aggressive treatment was performed, with higher frequency of total thyroidectomy (99 vs. 78%; p = 0.003), lymph node dissection (41 vs. 15%; p = 0.005) and therapy with radioactive iodine (96 vs. 73%; p = 0.002). Tumor stage was similar in both groups (p = 0.237), with a higher number of T3 cases in the group B (24 vs. 5%; p = 0.009). After a mean follow-up of 90 ± 68.95 months, the oncological results were similar, with a similar disease persistence rate (9 vs. 5%; p = 0.337), disease recurrence rate (21 vs. 8%; p = 0.159) and disease-free survival (p = 0.075). CONCLUSIONS: Unicentric FPTMC should not be considered as a SPTMC due to its prognosis is similar to multicentric FPTMC.

Biological behavior of familial papillary thyroid microcarcinoma: Spanish multicenter study.

PURPOSE: Familial papillary thyroid microcarcinoma (FPTMC) can present a more aggressive behavior than the sporadic microcarcinoma. However, few studies have analyzed this situation. The objective is to analyze the recurrence rate of FPTMC and the prognostic factors which determine that recurrence in Spain. METHODS: Spanish multicenter longitudinal analytical observational study was conducted. Patients with FPTMC received treatment with curative intent and presented cure criteria 6 months after treatment. Recurrence rate and disease-free survival (DFS) were analyzed. Two groups were analyzed: group A (no tumor recurrence) vs. group B (tumor recurrence). RESULTS: Ninety-four patients were analyzed. During a mean follow-up of 73.3 ± 59.3 months, 13 recurrences of FPTMC (13.83%) were detected and mean DFS was 207.9 ± 11.5 months. There were multifocality in 56%, bilateral thyroid involvement in 30%, and vascular invasion in 7.5%; that is to say, they are tumors with histological factors of poor prognosis in a high percentage of cases. The main risk factors for recurrence obtained in the multivariate analysis were the tumor size (OR: 2.574, 95% CI 1.210-5.473; p = 0.014) and the assessment of the risk of recurrence of the American Thyroid Association (ATA), both intermediate risk versus low risk (OR: 125, 95% CI 10.638-1000; p < 0.001) and high risk versus low risk (OR: 45.454, 95% CI 5.405-333.333; p < 0.001). CONCLUSION: FPTMC has a recurrence rate higher than sporadic cases. Poor prognosis is mainly associated with the tumor size and the risk of recurrence of the ATA.

Evaluating the impact of the learning curve on the perioperative outcomes of robot-assisted radical cystectomy with intracorporeal urinary diversion.

INTRODUCTION: Robot-assisted radical cystectomy (RARC) with intracorporeal urinary diversion (ICUD) is a technically difficult procedure. Our aim was to evaluate the potential impact of the learning curve (LC) on perioperative and pathological outcomes of RARC with ICUD. MATERIAL AND METHODS: Retrospective study of 62 consecutive patients who underwent RARC with ICUD for bladder cancer between 2015-2020. We compared 3 consecutive groups of 20 (G1), 20 (G2), and 22 (G3) patients to analyze the impact of the LC. G1 cases were performed by a senior surgeon experienced in robotic surgery, while G2-G3 were performed by 2 junior surgeons without experience under the mentorship of the senior surgeon. RESULTS: The 3 groups had similar clinical and pathological characteristics. A total of 15 patients (24%) received a neobladder and 47 (75%) an ileal conduit. The mean operative time decreased 60 min between G1-G3 (p = 0.001). No conversions to open approach or intraoperative complications were reported. There were no differences between groups regarding positive margin rates (p = 0.6) or the number of lymph nodes removed (p = 0.061). The postoperative complication rate was 77% and did not change during the LC (p = 0.49). Uretero-enteric stricture rate decreased from 25% in G1 to 9% in G3 (p = 0.217). CONCLUSIONS: The inclusion of junior surgeons to a RARC with ICUD program after the initial 20 cases does not have an impact on the perioperative and pathological outcomes of the procedure. The operative time and the uretero-enteric stricture rate could be reduced during the LC.

Evaluating the impact of the learning curve on the perioperative outcomes of robot-assisted radical cystectomy with intracorporeal urinary diversion. / Análisis del impacto de la curva de aprendizaje de la cistectomía radical asistida por robot con derivación urinaria intracorpórea sobre los resultados perioperatorios.

INTRODUCTION: Robot-assisted radical cystectomy (RARC) with intracorporeal urinary diversion (ICUD) is a technically difficult procedure. Our aim was to evaluate the potential impact of the learning curve (LC) on perioperative and pathological outcomes of RARC with ICUD. MATERIAL AND METHODS: Retrospective study of 62 consecutive patients who underwent RARC with ICUD for bladder cancer between 2015-2020. We compared 3 consecutive groups of 20 (G1), 20 (G2), and 22 (G3) patients to analyze the impact of the LC. G1 cases were performed by a senior surgeon experienced in robotic surgery, while G2-G3 were performed by 2 junior surgeons without experience under the mentorship of the senior surgeon. RESULTS: The 3 groups had similar clinical and pathological characteristics. A total of 15 patients (24%) received a neobladder and 47 (75%) an ileal conduit. The mean operative time decreased 60minutes between G1-G3 (P=0.001). No conversions to open approach or intraoperative complications were reported. There were no differences between groups regarding positive margin rates (P=0.6) or the number of lymph nodes removed (P=0.061). The postoperative complication rate was 77% and did not change during the LC (P=0.49). Uretero-enteric stricture rate decreased from 25% in G1 to 9% in G3 (P=0.217). CONCLUSIONS: The inclusion of júnior surgeons to a RARC with ICUD program after the initial 20 cases does not have an impact on the perioperative and pathological outcomes of the procedure. The operative time and the uretero-enteric stricture rate could be reduced during the LC.

Assessment of saliva and oral candidiasis levels 12, 24 and 36 months after radiotherapy in patients with head and neck cancer.

INTRODUCTION: Hyposalivation is a serious complication during radiotherapy (RT) and it is one of the major risk factors for the presence of candidiasis. The aim of this study was to evaluate the salivary hypofunction during the different stages of RT, analysing its connection with the presence of candidiasis. MATERIAL AND METHODS: A retrospective study was performed in 83 patients who had been diagnosed with head and neck tumours and who were undergoing RT treatment. Their salivary function was clinically analysed throughout the course of the RT treatment (before, during and after treatment) by means of the whole saliva test (WST), both unstimulated (WST-I) and stimulated (WST-II), and its relationship with candidiasis was evaluated using culture-based methods. RESULTS: The WST-I before RT was 37.24±17.36mm and the WST-II was 60.70±30.98mm, with 47% of patients testing positive for candidiasis. The prevalence of candidiasis increased up to 55.8% during RT and it returned to similar pre-RT levels at the end of treatment (45.2%). A statistical significant relationship was found between low WST-I and candidiasis in the 1st (13.58 vs 20.78mm), 3rd (18.06 vs 24.36mm), 6th (16.83 vs 24.5) and 12th (16 vs 28.74mm) months after RT; and this relationship was also detected for WST-II in the 1st (24.73 vs 41.26mm) and 3rd (27.71 vs 39.91mm) months after RT. Female sex was identified as an independent associated risk factor for mild hyposalivation before RT (OR=6.50, CI: 95% 1.77-23.93, p=0.005) and glandular hypofunction (OR=3.01, CI: 95% 1.12-8.10, p=0.029). DISCUSSION: There is a clear relation between hyposalivation and the presence of candidiasis during and after RT. Larger studies must be performed in order to further elucidate this effect.

Current status of genetic urinary biomarkers for surveillance of non-muscle invasive bladder cancer: a systematic review.

BACKGROUND: Genetic biomarkers are a promising and growing field in the management of bladder cancer in all stages. The aim of this paper is to understand the role of genetic urinary biomarkers in the follow up of patients with non muscle invasive bladder cancer where there is increasing evidence that they can play a role in avoiding invasive techniques. METHODS: Following PRISMA criteria, we have performed a systematic review. The search yielded 164 unique articles, of which 21 articles were included involving a total of 7261 patients. Sixteen of the articles were DNA based biomarkers, analyzing different methylations, microsatellite aberrations and gene mutations. Five articles studied the role of RNA based biomarkers, based on measuring levels of different combinations of mRNA. QUADAS2 critical evaluation of each paper has been reported. RESULTS: There are not randomized control trials comparing any biomarker with the gold standard follow-up, and the level of evidence is 2B in almost all the studies. Negative predictive value varies between 55 and 98.5%, being superior in RNA based biomarkers. CONCLUSIONS: Although cystoscopy and cytology are the gold standard for non muscle invasive bladder cancer surveillance, genetic urinary biomarkers are a promising tool to avoid invasive explorations to the patients with a safe profile of similar sensitivity and negative predictive value. The accuracy that genetic biomarkers can offer should be taken into account to modify the paradigm of surveillance in non muscle invasive bladder cancer patients, especially in high-risk ones where many invasive explorations are recommended and biomarkers experiment better results.

A comparative study of different surgical techniques for the management of distal ureter during laparoscopic radical nephroureterectomy. / Estudio comparativo de diferentes técnicas quirúrgicas para el manejo del uréter distal durante la nefroureterectomía laparoscópica.

OBJECTIVES: To compare the oncological outcomes between two open surgical techniques and two endoscopic approaches for the management of the distal ureter during laparoscopic radical nephroureterectomy (LRNU). MATERIAL AND METHODS: Retrospective review of 152 patients submitted to LRNU for the management of upper urinary tract tumors between 2007-2014. We analyzed the potential impact of two different open surgical (extravesical vs intravesical) and two endoscopic (resection of ureteral orifice and fragment removal vs endoscopic bladder cuff) techniques on the development of bladder recurrence, distant/local recurrence and cancer-specific survival (CSS). RESULTS: A total of 152 patients with a mean age of 69.9 years (±10.1) underwent LRNU. We reported 62 pTa-T1 (41%), 35 pT2 (23%) and 55 pT3-4 (36%). Thirty-two were low grade (21.1%) and 120 high grade (78.9%). An endoscopic approach was performed in 89 cases (58.5%), 32 with resection (36%) and 57 with bladder cuff (64%), and open approach in 63 (41.5%), 42 intravesical (66.7%) and 21 extravesical (33.3%). Within a median follow-up of 32 months (3-120), 38 patients (25%) developed bladder recurrence, 42 distant/local recurrence (27.6%) and 34 died of tumor (22.4%). In the univariate analysis, the type of endoscopic technique was not related to bladder recurrence (P=.961), distant/local recurrence (P=.955) nor CSS (P=.802). The open extravesical approach was not related to bladder recurrence (P=.12) but increased distant/local recurrence (P=.045) and decreased CSS (P=.034) compared to intravesical approach. CONCLUSIONS: LRNU outcomes are not dependant on the type of endoscopic approach performed. The open extravesical approach is a more difficult technique and could worsen the oncological outcomes when compared to the intravesical.

Comparison of perioperative outcomes and complications of robot assisted radical cystectomy with extracorporeal vs intracorporeal urinary diversion. / Comparación de los resultados perioperatorios de la cistectomía radical asistida por robot con derivación urinaria extracorpórea vs. intracorpórea.

OBJECTIVES: To compare perioperative outcomes and complications of robot assisted radical cystectomy (RARC) with extracorporeal (ECUD) vs. intracorporeal urinary diversion (ICUD) for bladder cancer. MATERIAL AND METHODS: Retrospective revision of 43 patients who underwent RARC for bladder cancer between 2015-2018 with at least 3 months of follow-up. The analysis included the initial series of RARC performed by one surgeon with extensive experience in open radical cystectomy. RESULTS: Forty-three patients, 40 men (93%) and 3 women (7%), with a median age of 65 years (44-83) and mean follow-up of 27.7 months (±20.1) underwent RARC. A ECUD was performed in 22 cases (51%), of whom 10 were ileal conduits (45.5%) and 12 neobladders (54.5), and ICUD in 21 cases (49%), of whom 14 were ileal conduits (66.7%) and 7 neobladders (33.3%). Clinical and preoperative characteristics were similar in both groups. The median operative time was 360 minutes (240-540) and length of hospital stay was 12 days (7-73). Thirty-five patients (81%) had postoperative complications, of whom 10 (23%) were major. Operative time, peroperative complications, pathological stage, positive margins, and number of lymph nodes removed did not significantly differ among groups. Patients who underwent ECUD had a higher rate of uretero-ileal strictures than those with ICUD (45.5% vs. 14.3%, P=.026). Among the neobladders, the ECUD developed a higher rate of urethro-neobladder stricture than the ICUD (33% vs. 0%, P=.044). CONCLUSIONS: RARC with ICUD achieved peroperative outcomes and complication rates comparable than those with ECUD. The ICUD could reduce the risk of developing uretero-ileal and urethro-neobladder strictures.

Survival study of leukoplakia malignant transformation in a region of northern Spain.

BACKGROUND: Oral leukoplakia is the most common potentially malignant disorder (PMD) of the oral cavity. The objectives of this study are to determine the clinicopathologic features in a group of patients with oral leukoplakia of Northern Spain (Galicia), determining the factors associated to clinical risk and analyzing the malignant transformation of these patients. MATERIAL AND METHODS: We included 85 patients. We recorded sex and age, habits like alcohol and tobacco, size, clinical appearance, site, number of lesions, and presence or absence of dysplasia. We assess the association between risk factors and transformation and developed a logistic regression analysis. Finally we used the Kaplan-Meier and log-rank test for the survival analysis. RESULTS: 7 patients (8.2%) had malignant transformation. The mean follow-up of the patients was 4.13 years versus 5.58 years of those who developed carcinoma. Only location and initial dysplasia have a statistically significant relationship with malignant transformation, but when applied the long rank test only the presence of dysplasia remains statistically significant(P<0,026). Oral Cancer Free Survival was 81.9% (0.150) at 11 years for the group without dysplasia. CONCLUSIONS: We found that the presence of dysplasia is the only risk factor that is statistically related to the development of a carcinoma.

Office stent placement under local anesthesia is a safe and efficient procedure for the management of multiple ureteral disorders. / La colocación de catéteres doble J con anestesia local en régimen ambulatorio es un procedimiento seguro y eficiente para el manejo de distintas patologías ureterales.

OBJECTIVE: To assess the outcomes of ureteral stent placement under local anesthesia for the management of multiple ureteral disorders. METHODS: Retrospective study of 45 consecutive ureteral stents placed under local anesthesia from January 2015 to July 2016. Inclusion criteria were hemodynamically stable patients with urinary obstruction, urinary fistula or for prophylactic ureteral localization during surgery. Five minutes before the procedure, 10ml of lidocaine gel and 50ml of lidocaine solution were instilled in the bladder. A 4.8Fr ureteral stent was placed using a 15.5Fr flexible cystoscope under fluoroscopic control. Characteristics of procedures and outcomes were analysed. RESULTS: A total of 45 procedures (33 placement, 12 replacements) were attempted in 37 patients, of which 40 (89%) were successful. There were 10 male (27%) and 27 female patients (73%) with a mean age of 58.6 years (±17.5). Main indications for stent placement were stones (37.8%), extrinsic ureteral compression (28.9%) and surgery ureteral localization (22.2%). The reasons for failing to complete a procedure were the inability to pass the guidewire/stent in 4 cases (8.8%) or to identify the ureteral orifice in 1 (2.2%). Postoperative complications occurred in 8 patients (17.8%) (7 Clavien I, 1 Clavien IIIa). No procedure was prematurely terminated due to pain. Statistical analysis did not find significant successful predictors. The outpatient setting provided a fourfold cost decrease. CONCLUSIONS: Ureteral stent placement can be safely and effectively performed under local anesthesia in the office cystoscopy room. This procedure could free operating room time, reduce costs and minimize side effects of general anesthesia.

The Patient's Comorbidity Burden Correlates with the Erectile Dysfunction Severity. / El peso de la comorbilidad del paciente se correlaciona con la gravedad de la disfunción eréctil.

OBJECTIVE: To explore the potential relationship between erectile dysfunction (ED), low testosterone levels, and the Charlson Comorbidity Index (CCI). MATERIAL AND METHODS: Cross-sectional study on patients referred to the andrology unit in 7 Spanish centers. The ED was diagnosed and graded using the International Index of Erectile Function (IIEF-5) score. Total testosterone, the prevalence of each comorbidity, and the CCI were compared between patients with different grades of ED. Besides, the correlation between total testosterone and the CCI score, the influence of each comorbidity, and the ED severity on the CCI was assessed in a multiple linear regression. RESULTS: The study included 430 men with a mean age of 61 years. The mean CCI was 3.5, and mean total testosterone 15.2 nmol/L; 389 (91%) subjects had some grade of ED: 97 (23%) mild, 149 (35%) mild-to-moderate, 86 (20%) moderate, and 57 (13%) severe. The increase in ED severity was significantly associated with a decrease in total testosterone (P=.002), and an increase in the CCI score (P<.001). Testosterone levels were significantly lower in patients with obesity, diabetes, hypercholesterolemia, and hypertriglyceridemia (P<.05). However, only the prevalence of diabetes and hypertension was significantly associated with the severity of ED. The multivariate analysis including variables related to all assessed comorbidities, total testosterone levels, and the DE severity significantly predicted the CCI score (P<.001, R2=.426). The severity of ED significantly contributed to this model (P=.011), but total testosterone did not (P=.204). CONCLUSIONS: The CCI is significantly associated with the ED severity, but it shows a weak correlation with the testosterone levels.

¿Conoce cuál es su riesgo de tener diabetes? / Do you know your risk of having diabetes?

La diabetes mellitus tipo 2 (DM2) es una enfermedad silenciosa que afecta hasta el 20% de nuestra población y de ella, hasta el 50% desconoce que la padece. Esta enfermedad se asocia a una alta prevalencia sobre factores de riesgo como el sobrepeso, la obesidad y la inactividad física. Con frecuencia, la DM2 se diagnostica en forma tardía y a veces genera diversas complicaciones asociadas que podrían evitarse

Etiología y perfil de resistencia antimicrobiana en infecciones del pie diabético / Etiology and antimicrobial resistance profile in diabetic foot infections

El pie diabético infectado (PDI) es aquel que presenta infección de piel y partes blandas u óseas por debajo del maléolo; constituye la complicación más frecuente de diabetes que causa hospitalización y amputación. En nuestro hospital los pacientes con pie diabético son asistidos en un consultorio multidisciplinario; el 40% presenta infección leve moderada o grave

A higher Charlson comorbidity index is related to more aggressive characteristics in de novo vesical tumours.

OBJECTIVE: To analyze the relationship between the age--adjusted Charlson Comorbidity Index (aCCI) and pathological outcomes of transurethral resection of de novo bladder tumours (BT). MATERIAL AND METHODS: Data from 208 patients who underwent a transurethral resection (TUR) of a de novo BT between 2007 and 2008 were collected. We recorded the following variables: age, sex, tobacco consumption, comorbidities assessed according to the ICCa (score and mortality rate), disease stage, tumour grade and risk of recurrence and progression. The relationship between the preoperative variables and the final pathological characteristics was analyzed. The multivariate study was conducted with the significant variables (P<.05) from the univariate analysis. RESULTS: The mean age of the patients was 69.5 ± 12 years, and 77% were men. The mean ICCa was 6.4 ± 2.5. The final pathology results showed a Tx, T0, Ta, T1 and T ≥ 2 in 5.3, 6.7, 31.7, 26.9, and 28.8% of the cases, respectively. 33.3% of the tumours were low-grade and 66.7% were high-grade. 14.3% of the tumours were associated with carcinoma in situ. Among those non musculo-invasive bladder tumour (non-MIBT), 34.7% had a low risk of recurrence and progression, 18.1% had an intermediate risk and 47.2% had a high risk. The patients with a ICCa ≥ 5 had an increased number of MIBT (RR: 2.29; 1.1-4.8; P=.032), high-grade tumours (RR: 3.1; CI: 1.6-6; P=.001) and tumours with a high risk of recurrence and progression (RR: 2.9; CI: 1.4-5.9; P<.001). CONCLUSION: The ICCa is related to the pathological characteristics of de novo BT. Patients with greater comorbidity can present more aggressive tumours. The ICCa could therefore be useful in clinical practice for identifying patients with worse prognosis.

Predictors, pathological characteristics and outcomes of bladder recurrences following nephroureterectomy.

OBJECTIVES: To analyze the predictors for bladder recurrence (BR) after nephroureterectomy (NU) for upper urinary tract tumors (UUTT), as well as its pathological characteristics, outcomes and impact on survival. MATERIAL AND METHODS: Retrospective study of 117 patients who underwent laparoscopic nephroureterectomy by UUTT between 2007-2012 at our center. The potential predictors for BR were analyzed using Cox regression; Kaplan-Meier curves were employed to study survival. RESULTS: The sample was composed of 85 men (73%) and 32 women (27%), with a mean age of 70 years. After a mean follow-up of 26 months, 23 patients presented BR (19.6%). In the multivariate analysis, sex (p=.003; HR [female], 3.8) and the location of the UUTT in the distal ureter (p=.002; HR, 4.8) were independent predictors for BR. The median time to BR was 8 months. Fifteen patients presented a nonmuscle-invasive BR (65.2%), and 8 presented a muscle-invasive BR (34.8%). All BRs, except for 2, appeared during the first 2 years. Five cases with nonmuscle-invasive BR presented a new BR. Six patients with muscle-invasive BR died before it could be determined whether cause of death was the BR or an UUTT relapse. The onset of BR showed no repercussion on the survival of patients with UUTT. CONCLUSIONS: Sex (female) and the location of the UUTT (distal ureter) are predictors for BR after NU. Patients with these characteristics might benefit from adjuvant intravesical treatment and closer monitoring. The onset for RV has no impact on the survival of patients with UUTT.

Renal transplantation in children with nephrotic syndrome in the first year of life.

OBJECTIVE: The aim of this work was to analyze the evolution of the 1st renal transplantation in children with nephrotic syndrome in the 1st year of life (NSFL). METHODS: In this retrospective study of 15 patients (8 women and 7 men) with NSFL receiving transplants from 1989 to 2013, 9 had NS of Finnish type, 4 diffuse mesangial sclerosis, 1 minimal changes, and 1 collapsing glomerulopathy. We analyzed the clinical and analytic situation at 4 time points: before dialysis, before transplantation, 3 months after transplantation, and long-term evolution. RESULTS: Mean follow-up was 72.8 months (range, 1 month to 16.9 years); mean age at diagnosis was 2.21 months (range, 0-8.2 months); mean age at onset of replacement therapy was 22.9 ± 16.4 months (range, 3.8-55.4 months); and mean time on dialysis was 14.9 months (range, 2-44 months). Age at transplantation was 3.1 years (range, 1.8 to 7.7 years), with 6 living-donor transplantations (LDTs) and 9 cadaveric (CDTs). Ten patients required nephrectomy before transplantation (9 bilateral) to control proteinuria after 3.1 ± 3.8 months on dialysis, 1 during transplantation, and 3 after transplantation (2 persistent proteinuria, 1 hypertension). Mean time on dialysis for LDTs was 5.4 ± 2.7 months versus 13.2 ± 6.9 months for CDTs (P < .005). Mean age of cadaveric donors was 6.2 ± 2.4 years and that of living donors 35.5 ± 7.9 years. As complications, there was 1 bleeding from venous anastomosis and 1 urinary leakage after surgery. After 6 ± 5.2 years of evolution, actuarial survival at both 1 and 7 years was 92.9%. One graft was lost owing to acute rejection 1 month after transplantation and 2 others owing to chronic rejection >9 years after transplantation. None had disease recurrence. CONCLUSIONS: Short-term complications did not differ from the rest of population if transplantation occurred with standard albumin levels, for which most required pre-transplantation nephrectomy because dialysis failed to reduce proteinuria.

BK virus infection in pediatric renal transplantation.

BACKGROUND: Polyomavirus BK (BKV) is a common complication after renal transplantation and an important cause of graft loss. The purpose of this study was to determine the incidence of BKV infection (viremia) in our population and to describe clinical features, global outcomes, and potential correlations with clinical or epidemiologic factors. METHODS: This retrospective single-center study included 84 pediatric recipients of kidney transplantation from January 2006 to September 2012. BKV infection screening consisted of periodic determination of decoy cells in urine samples, confirmed by means of quantitative polymerase chain reaction test in blood. RESULTS: Twenty-two patients (26%) developed BKV viremia. BKV replication appeared early after renal transplantation (median, 2 months). One-third of patients remained asymptomatic, and 27% presented elevated serum creatinine. Immunosuppression was reduced in 90% of patients, and 83% achieved clearance of viremia within 6 months. There was only 1 case of histologically confirmed BKV nephropathy, which evolved to graft loss despite leflunomide, intravenous immunoglobulins, and mycophenolate discontinuation. Risk of BKV viremia was associated with younger age at transplantation (5.9 y vs 10.9 years; P = .001) and cadaveric donor (relative risk, 3.2; P < .05). BKV infection did not affect short-term renal function and graft survival. CONCLUSIONS: BKV viremia is very common in the pediatric renal transplant population, especially in younger children and in those receiving a kidney from cadaveric donors. It develops in the 1st months after transplantation. Reduction of immunosuppression seems to be a good therapeutic option, with high rates of clearance of the infection, although the only patient with confirmed BKV nephropathy had poor outcome.

Fra-1/AP-1 induces EMT in mammary epithelial cells by modulating Zeb1/2 and TGFß expression.

Epithelial-to-mesenchymal transition (EMT) is essential for embryonic morphogenesis and wound healing and critical for tumour cell invasion and dissemination. The AP-1 transcription factor Fra-1 has been implicated in tumorigenesis and in tumour-associated EMT in human breast cancer. We observed a significant inverse correlation between Fra-1 mRNA expression and distant-metastasis-free survival in a large cohort of breast cancer patients derived from multiple array data sets. This unique correlation among Fos genes prompted us to assess the evolutionary conservation between Fra-1 functions in EMT of human and mouse cells. Ectopic expression of Fra-1 in fully polarized, non-tumourigenic, mouse mammary epithelial EpH4 cells induced a mesenchymal phenotype, characterized by a loss of epithelial and gain of mesenchymal markers. Proliferation, motility and invasiveness were also increased in the resulting EpFra1 cells, and the cells were tumourigenic and efficiently colonized the lung upon transplantation. Molecular analyses revealed increased expression of Tgfß1 and the EMT-inducing transcription factors Zeb1, Zeb2 and Slug. Mechanistically, Fra-1 binds to the tgfb1 and zeb2 promoters and to an evolutionarily conserved region in the first intron of zeb1. Furthermore, increased activity of a zeb2 promoter reporter was detected in EpFra1 cells and shown to depend on AP-1-binding sites. Inhibiting TGFß signalling in EpFra1 cells moderately increased the expression of epithelial markers, whereas silencing of zeb1 or zeb2 restored the epithelial phenotype and decreased migration in vitro and tumorigenesis in vivo. Thus Fra-1 induces changes in the expression of genes encoding EMT-related transcription factors leading to the acquisition of mesenchymal, invasive and tumorigenic capacities by epithelial cells. This study defines a novel function of Fra-1/AP-1 in modulating tgfb1, zeb1 and zeb2 expression through direct binding to genomic regulatory regions, which establishes a basis for future in vivo genetic manipulations and preclinical studies using mouse models.

Quantitative determination of c-myc facilitates the assessment of prognosis of OSCC patients.

Myc genes are a family of proto-oncogenes whose proteins are implicated in the regulation of cell proliferation, differentiation and apoptosis, and in regulating the activity of genes involved in cell division. The aim of the present study was to establish a quantitative description of the expression of c-myc and evaluate its relationship with other clinical and prognostic factors, as well as to establish a multivariate survival prediction model. This is a retrospective study of 68 patients diagnosed with oral squamous cell carcinoma (OSCC). We constructed a tissue microarray for investigating the expression of c-myc by immunohistochemistry. Statistical analyses were carried out, and a multivariate model that predicts survival was established. The average expression of c-myc was 50.32 (SD, 26.05) with a range from 6.60 to 99.48; similar for initial and advanced tumor stages. Non-smoking patients had higher levels of c-myc, showing statistically significant differences (Kruskal-Wallis χ2=5.975; p=0.05). We found no statistically significant relationship between the quantitative expression of c-myc and any other clinical or pathological parameters. For each unit of increase of c-myc, the risk increased by 1.15 (p<0.001; HR, 1.150; 95% CI, 1062-1245). Further study of this protein, which may have a significant diagnostic, prognostic and therapeutic value is warranted. Its determination can be valuable when used together with other markers to assess the prognosis of OSCC patients.