Novel FLNB Variants in Seven Argentinian Cases with Spondylocarpotarsal Synostosis Syndrome.

Spondylocarpotarsal synostosis syndrome (SCT) is a very rare skeletal dysplasia characterized by vertebral, carpal, and tarsal fusion; growth retardation; and mild dysmorphic facial features. Variants in FLNB, MYH3, and RFLNA have been implicated in this dysplasia. We report the clinical and radiological follow-up of seven SCT pediatric cases associated with biallelic FLNB variants, from four Argentinian families. The seven cases share previously described facial characteristics: round facies, large eyes, and wide based nose; all of them had variable height deficit, in one case noted early in life. Other findings included clinodactyly, joint limitation without bone fusion, neurosensorial hearing loss, and ophthalmological compromise. All cases presented with spinal fusion with variable severity and location, carpal bones coalition, and also delay in carpal ossification. The heterozygous carrier parents had normal height values to -2.5 score standard deviation, without skeletal defects detected. Three different FLNB variants, one nonsense and two frameshift, were detected, all of which were predicted to result in a truncated protein or are degraded by nonsense mediated decay. All cases had at least one copy of the nonsense variant, c.1128C> G; p. (Tyr376*), suggesting the presence of a common ancestor.

Pubertal growth in height, sitting height and leg length in achondroplasia.

Background: Children with achondroplasia (ACH) appear to lack a pubertal growth spurt in height.Aim To explore the growth spurt in height and its segments sitting height and leg length, in a large sample of ACH cases using growth curve modelling.Subjects and methods: Height and sitting height were measured longitudinally in ACH children, and the data were analysed using the SITAR (SuperImposition by Translation and Rotation) growth model, which estimates a mean growth curve and random effects for individuals defining differences in size, pubertal timing and intensity.Results: Out of 402 ACH children, 85 boys and 75 girls aged 7-20 years had respectively 529 and 454 measurements of height and sitting height, with leg length calculated by difference. SITAR analysis identified peaks in mean height velocity at 13.3 and 11.3 years in boys and girls, with peak velocities of 4.3 and 4.4 cm/year. Mean peak velocity for sitting height was 3.0 cm/year, but leg length showed no peak. The SITAR models explained 92% to 99% of the cross-sectional variance.Conclusion: ACH children do experience a growth spurt in puberty, but only half that of control children. The spurt is due entirely to sitting height, with no leg length spurt.

Vaginal fertility-sparing surgery and laparoscopic sentinel lymph node detection in early cervical cancer. Retrospective study with 15 years of follow-up.

OBJECTIVE: The aim of this study was to evaluate the oncological outcomes of vaginal fertility-sparing surgery plus laparoscopic sentinel lymph node biopsy in patients with early cervical cancer over a 15-years period. PATIENTS AND METHODS: From March 2005 to April 2018, 38 patients diagnosed with early stage cervical cancer underwent vaginal fertility-sparing surgery at the Hospital Clínic, Barcelona, Spain. Patients with FIGO stage IA1 with lymphovascular space invasion and stage IA2 underwent simple trachelectomy and patients with stage IB1 underwent radical vaginal trachelectomy. All cases underwent laparoscopic sentinel lymph node biopsy. In the first 19 cases, laparoscopic bilateral pelvic lymphadenectomy was completed immediately after sentinel lymph node biopsy. Clinical and oncological follow-up data were collected. RESULTS: The median age at diagnosis was 33.5 years (range 22-44). Simple trachelectomy was performed in seven cases (18.4%) and vaginal radical trachelectomy in 31 (81.6%). Nineteen patients were exclusively treated with laparoscopic sentinel lymph node biopsy and 19 with sentinel lymph node biopsy plus laparoscopic bilateral pelvic lymphadenectomy. There were no significant differences between the two lymph node assessment groups regarding histology and tumour size. The median follow-up was 73 months (range 1-160 months). There were 4 recurrences (3 patients with IB1 and 1 with IA2). Two occurred in the sentinel lymph node biopsy group and 2 in the sentinel lymph node biopsy plus laparoscopic bilateral pelvic lymphadenectomy group. All the recurrences were diagnosed in patients with adenocarcinoma and in 3 patients without lymphovascular space invasion. CONCLUSION: Vaginal fertility-sparing surgery combined with laparoscopic sentinel lymph node biopsy seems to be a safe oncological procedure in selected patients with early stage cervical cancer. Further studies are needed to clarify the role of sentinel lymph node biopsy in fertility- sparing surgery in cervical cancer. Adenocarcinoma histology seems to be an important risk factor for recurrence.

Is one brachytherapy fraction of 7 Gy similar to more fractions after external beam irradiation in postoperative endometrial carcinoma?

PURPOSE: To determine whether brachytherapy with a single hypofractionated dose of 7 Gy provides the similar vaginal-cuff relapses and safety profile in terms of complications compared to schedules of 2 or 3 fractions of lower doses in patients treated previously with external beam irradiation in postoperative endometrial carcinoma. METHODS/MATERIAL: From June 2003 to December 2016, 325 patients were treated with 3 different schedules of high-dose-rate brachytherapy after external beam irradiation for postoperative endometrial carcinoma. The patients were divided into 3 groups: Group-1: 125 patients were treated with 3 fractions of 4-6 Gy per fraction (3 fractions/week) between 2003 and 2008; Group-2: 93 patients were treated with 2 consecutive daily fractions of 5-6 Gy between 2008 and 2011; Group-3: 107 patients received a single fraction of 7 Gy between 2011 and 2016. Bladder and rectum complications were assessed using RTOG scores and with the objective scores of LENT-SOMA for the vagina. STATISTICS: the chi-square test. RESULTS: The mean follow-up of Groups 1, 2 and 3 was 95, 67 and 51 months, respectively. Three patients in Group-1, 2 in Group-2, 1 in Group-3 developed vaginal-cuff relapse (p = 0.68). No differences were found in late toxicity among the three groups. CONCLUSIONS: One single dose of 7 Gy is safe and effective and may be the best treatment schedule with a similar incidence of vaginal-cuff relapses, complications and patient comfort with less hospital attendance.

Quiste folicular pigmentado perianal: variante múltiple inusual / Perianal pigmented follicular cyst: unusual multiple variant

Los quistes foliculares pigmentados son quistes epiteliales muy infrecuentes. Se describen como lesiones papulares pigmentadas, de carácter benigno, que generalmente se ubican en la cabeza o cuello. Surgen de manera única, siendo la variante múltiple aún menos frecuente. A continuación, se presenta el caso de un hombre joven, con antecedentes de VIH en terapia antiretroviral, quien consultó por la presencia de múltiples lesiones perianales, asintomáticas, de larga data, cuyo resultado histológico resultó compatible con: quistes pigmentados foliculares múltiples.

Pigmented follicular cysts are a very rare epithelial cysts. They are described as a benign papular lesion, that is usually located in the head or neck. They arise as unique, being the multiple variant even less frequent. We present the case of a young man with a history of HIV in antiretroviral therapy, who consulted for the presence of multiple, long-term asymptomatic perianal lesions whose histological result was: compatible with multiple follicular pigmented cysts.

Comparison of the analytical and clinical performance of five tests for the detection of human papillomavirus genital infection.

HPV-based screening provides greater protection against cervical cancer (CC) than cytology-based strategies. Currently, several molecular diagnostic assays for the detection of human papillomavirus (HPV) are available. In this study, we analyzed 5 different HPV testing and genotyping techniques (Hybrid Capture 2 [HC2; Qiagen, Hilden, Germany], AnyplexTMII HPV28 [Anyplex; Seegene, Seoul, Korea], Linear Array [Roche, Branchburg, NJ, USA], GP5+/6+ PCR-EIA-RH [Labo Bio-medical Products, Rijswijk, The Netherlands] and CLART2 [Genomica, Madrid, Spain]) in 295 women referred to the hospital Colposcopy Clinic from 2007 to 2008 due to positive HPV test results or an abnormal Pap test. DNA extraction for HPV genotyping was performed in cervical sample specimens after Pap test and HPV detection by HC2. The inclusion criteria were: (1) adequate cervical sampling with sufficient material for the Pap test and HPV detection and genotyping, and (2) colposcopically-directed biopsy and/or endocervical curettage. HC2 showed the highest sensitivity for high-grade squamous intraepithelial lesion and CC (HSIL+) detection (96.1%), but all the HPV genotyping tests showed a higher specificity. (Anyplex 86.8%; Linear Array 86.0%; GP5+/6+ 78.8%; CLART2 76.5%). The agreement between HC2 results and the other techniques was similar: 82.4%, kappa=0.650 for Anyplex; 83.4%, kappa=0.670 for Linear Array, 79.93%, kappa=0.609 for GP5+/6+ and 82.4%, kappa=0.654 for CLART2. HPV 16 and/or 18 infection was a risk factor for underlying HSIL+ in the univariate analysis. Anyplex showed the highest risk of underlying HSIL+ after positive HPV 16 and/or 18 tests (OR 31.1; 95% CI 12.1-80.0).

HPV testing in first-void urine provides sensitivity for CIN2+ detection comparable with a smear taken by a clinician or a brush-based self-sample: cross-sectional data from a triage population.

OBJECTIVE: To compare the sensitivity of high-risk human papillomavirus (hrHPV) and genotype detection in self-collected urine samples in the morning (U1), and later on (U2), brush-based self-samples (SS), and clinician-taken smears (CTS) for detecting cervical intraepithelial neoplasia grade 2+ (CIN2+) in a colposcopic referral population. DESIGN: Cross-sectional single-centre study. SETTING: A colposcopy clinic in Spain. POPULATION: A cohort of 113 women referred for colposcopy after an abnormal Pap smear. METHODS: Women undergoing colposcopy with biopsy for abnormal Pap smears were sent a device (Colli-Pee™, Novosanis, Wijnegem, Belgium) to collect U1 on the morning of colposcopy. U2, CTS, and SS (Evalyn brush™, Rovers Medical Devices B.V., Oss, the Netherlands) were also analysed. All samples were tested for HPV DNA using the analytically sensitive SPF10-DEIA-LiPA25 assay and the clinically validated GP5+/6+-EIA-LMNX. MAIN OUTCOME MEASURES: Histologically confirmed CIN2+ and hrHPV positivity for 14 high-risk HPV types. RESULTS: Samples from 91 patients were analysed. All CIN3 cases (n = 6) tested positive for hrHPV in CTS, SS, U1, and U2 with both HPV assays. Sensitivity for CIN2+ with the SPF10 system was 100, 100, 95, and 100%, respectively. With the GP5+/6+ assay, sensitivity was 95% in all sample types. The sensitivities and specificities for both tests on each of the sample types did not significantly differ. There was 10-14% discordance on hrHPV genotype. CONCLUSIONS: CIN2+ detection using HPV testing of U1 shows a sensitivity similar to that of CTS or brush-based SS, and is convenient. There was substantial to almost excellent agreement between all samples on genotype with both hrHPV assays. There was no advantage in testing U1 compared with U2 samples. TWEETABLE ABSTRACT: Similar CIN2+ sensitivity for HPV testing in first-void urine, physician-taken smear and brush-based self-sample.

Small lesion size measured by colposcopy may predict absence of cervical intraepithelial neoplasia in a large loop excision of the transformation zone specimen.

OBJECTIVE: To evaluate whether colposcopic measurement of the lesion size at diagnosis and/or human papillomavirus (HPV) genotyping can predict the absence of dysplasia in a large loop excision of the transformation zone (LLETZ) specimen in women treated for squamous intraepithelial lesions/cervical intraepithelial neoplasia (SIL/CIN). DESIGN: Prospective observational study. SETTING: Tertiary university hospital. POPULATION: A cohort of 116 women who underwent LLETZ because of biopsy-proven low-grade SIL/CIN that had persisted for 2 years, or because of a high-grade SIL/CIN diagnosed in the referral visit and squamocolumnar junction completely visible (types 1 or 2, according to the International Federation of Cervical Pathology and Colposcopy, IFCPC). METHODS: After LLETZ the women were classified by histology into the study group (absence of SIL/CIN in the surgical specimen, 28/116, 24.1%) and the control group (SIL/CIN in the LLETZ specimen, 88/116, 75.9%). MAIN OUTCOME MEASURES: The size of the lesion determined in the diagnostic colposcopy and the HPV genotype were evaluated in all women. RESULTS: The lesion size was significantly smaller in the study group (25.7 ± 37.8 versus 84.5 ± 81.7 mm2 ; P < 0.001). A lesion size of ≤12 mm2 and HPV types other than 16 or 18 were associated with an absence of SIL/CIN in the LLETZ specimen (P < 0.001 and P = 0.016, respectively). On multivariate analysis only a lesion size of ≤12 mm2 predicted the absence of SIL/CIN (odds ratio, OR 10.6; 95% confidence interval, 95% CI 3.6-30.6; P < 0.001). A lesion size of ≤12 mm2 had a specificity of 90.9% (95% CI 83.0-95.3%) and a negative predictive value of 86.0% (95% CI 77.5-91.6%) to predict the absence of SIL/CIN in the surgical specimen. CONCLUSIONS: Small lesion size in diagnostic colposcopy could predict the absence of SIL/CIN in the LLETZ specimen. Colposcopy measurement of lesion size prior to LLETZ may avoid unnecessary treatment. TWEETABLE ABSTRACT: Small lesion size in colposcopic evaluation might predict the absence of SIL/CIN in an LLETZ specimen.

Referencias argentinas de estatura sentada y longitud de miembros inferiores de 0 a 18 años / Argentine reference values for sitting height and lower limb length between 0 and 18 years of age

Para el seguimiento del crecimiento de niños con severa malformación de miembros inferiores o de columna, disponer de referencias de estatura sentada (ES) y de miembros inferiores (MI) según edad es una herramienta de gran utilidad. Objetivos: estimar los centilos de ES y MI para ambos sexos, entre 0 a 18 años de edad y evaluar la utilidad de estas referencias en niños con malformaciones localizadas en MI o columna. Material y Métodos: los centilos 3°,10°, 25°, 50°, 75°, 90° y 97° de ES y MI según Edad (SE/E y MI/E) fueron estimados en una población sana de 4803 y 4818 varones y mujeres respectivamente, por el método LMS que utiliza la transformación BOX-COX para normalizar la distribución de los datos a cada edad. Resultados: en los primeros años de edad, la mediana de ES en ambos sexos fue similar. Entre los 11 y 13 años, las niñas tuvieron una ES mayor a la de los varones, pero luego se invirtió y se mantuvo así hasta la adultez. En MI la mediana también fue similar en ambos sexos durante los primeros años, pero a partir de los 12 el incremento fue mayor en los varones. A los 12 años la diferencia fue 0,71 cm, finalizando con 9 cm a los 18 años. El uso de estas referencias en niños con malformaciones de columna ó MI mostró un crecimiento patológico de estatura total y del segmento corporal comprometido, con un tamaño y crecimiento normal del segmento no afectado. Conclusión: los centilos de segmentos corporales según la edad constituyen una herramienta útil para la supervisión del crecimiento de niños con severa malformación de columna o miembros inferiores (AU)

For the follow-up of growth of children with severe lower-limb or spinal deformities, reference values for sitting height (SH) and lower-limb (LL) length according to age are extremely useful. Aims: To define percentiles of SH and LL for both sexes between 0 and 18 years of age and evaluate the usefulness of these references in children with LL or spinal deformities. Material and Methods: 3rd,10th, 25th, 50th, 75th, 90th, and 97th percentiles for SH and LL according to age (SE/age and LL/age) were estimated for a healthy population of 4803 and 4818 boys and girls, respectively, with the LMS method that uses the Box-Cox power exponential (BCPE) to normalize data distribution for age. Results: In the first years of life, mean SH was similar for both sexes. Between 11 and 13 years of age, girls had a greater SH than boys, but this relationship subsequently inverted and remained so until adulthood. The median length of LL was also similar in the first years of life, but after 12 years of age growth was increased in boys. At 12 years of age the difference was 0.71 cm, with a final difference of 9 cm at 18 years of age. The use of these reference values in children with spinal or LL deformities showed pathological growth of the whole body and the body segment involved with normal growth of the nonaffected segment. Conclusion: percentiles of the body segments according to age are a useful tool for the monitoring of growth of children with severe deformities of the spine or lower limbs (AU)

PrEFiNe Plan: Strategic plan for Fabry diseases in Nephrology. / Plan PrEFiNE: Plan estratégico para la enfermedad de Fabry en Nefrología.

BACKGROUND: Renal failure is one of the main causes of death in patients with Fabry disease (FD). Due to the low prevalence of FD, delayed diagnosis and misdiagnosis, often the correct diagnosis is made when organ damage is already present. Early recognition of the disease would allow the prevention of severe complications and the premature death of patients with FD. OBJECTIVE: We present here the PrEFiNE project, which includes a wide spectrum of activities with the aim of improve knowledge and diagnosis of FD. The project is sponsored by Shire Iberia (http://shireiberica.com/) METHODS: From January 2016 to the end of 2017 several activities will be carried out, starting with a survey to evaluate current FD knowledge among nephrologists; in addition some studies to assess prevalence of this disease will be performed. One study will include patients receiving dialysis, another study will cover kidney transplant patients, and a pilot study in chronic kidney disease in stage 3-5 predialysis. Also planned is a pharmacoeconomic study to focus on burden of FD. At the same time medical education activities will be conducted both on line and on site. Plan for dissemination will include medical publications and diffusion to media. PrEFiNE Project will finish with the publication of a compilation book on FD in Nephrology including all planned activities and proposing recommendations based on results and detected unmet needs. PrEfiNE Plan will be coordinated by severa scientific committees, one at national level and 10 other regionals comittees, tha will be responsible to ensure the maximum scientific quality of proposed activities. An advisory board will supervise the project. DISCUSSION: PrEfiNE project will evaluate an action plan focused on improving FD knowledge to make necessary recommendations for an early recognition of the disease. In addition will generate a plan to improve previously undetected needs.

Cancer antigens 19.9 and 125 as tumor markers in patients with mucinous ovarian tumors.

PURPOSE OF INVESTIGATION: To determine the accuracy of carcinoembryonic antigen (CEA), cancer antigen (CA) 15.3, CA 19.9, and CA 125 for diagnosis of mucinous ovarian cancer (MOC). MATERIALS AND METHODS: Samples were collected preoperatively from patients with mucinous ovarian tumor. The following variables were analysed: CEA, CA 15.3, CA 19.9, and CA 125. After surgery, histology and stage were determined according to FIGO-classification. Patients were classified into two groups according to the diagnosis of ovarian biopsy: NOT MOC and MOC. RESULTS: The authors studied 94 patients with ages between 15 and 80 years (median = 43). Eighty-two patients were NOT MOC (68 mucinous ovarian cystadenomas and 14 mucinous borderline ovarian tumors) and 12 were MOC. All MOC patients were in FIGO Stages I or II. No statistically significant differences were found between MOC and NOT MOC patients according to CEA and CA 15.3 (p > 0.05). All MOC patients had abnormal serum CA 19.9 and/or CA 125 levels. Using CA 19.9 and CA 125, we performed a linear regression formula CA 19.9+125 = 0.00102 x CA 19.9 + 0.00057 x CA 125. AUCs values were 0.862 (p = 0.0002), 0.829 (p = 0.0021), and 0.911 (p = 0.0001) for CA 19.9, CA 125, and CA 19.9 + 125, respectively. CA 19.9 + 125 exhibited 95.1% specificity and 66.7% sensitivity, increased by 16.7% sensitivity compared with using only CA 19.9 or CA 125. CONCLUSIONS: Preoperative CA 19.9 and CA 125 levels showed high diagnosis efficacy to predict whether a mucinous ovarian tumour is benign or malignant. Using both markers simultaneously increases the sensitivity for diagnosis of MOC.

HPV-negative carcinoma of the uterine cervix: a distinct type of cervical cancer with poor prognosis.

OBJECTIVE: Using highly sensitive polymerase chain reaction (PCR) techniques, we reanalysed all cervical carcinomas (CCs) found to be human papillomavirus (HPV)-negative by Hybrid Capture 2 (HC2) to determine the prevalence of true HPV-negativity. We also evaluated the characteristics of the patients with tumours with confirmed HPV-negativity. DESIGN: Observational study. SETTING: Barcelona, Spain. POPULATION: A cohort of 136 women with CC (32 adenocarcinomas, 104 squamous cell carcinomas) who had pre-treatment HC2 testing. METHODS: All negative cases were reanalysed and genotyped for HPV using three PCR assays (SPF10, GP5+/6+ and E7-specific assay). MAIN OUTCOME MEASURES: Percentage of confirmed HPV-negative and HPV-positive tumours. Clinicopathological features and disease-free survival (DFS) and overall survival (OS) of both groups. RESULTS: Fourteen of 136 women (10.2%) were negative for HPV by HC2. After reanalysis by PCR-based techniques only 8/136 (5.8%) tumours were confirmed as HPV-negative, whereas in six cases different HPVs were identified [HPV-11, -16 (two tumours), -18, -45, and -68]. Confirmed HPV-negativity was more frequent in adenocarcinomas than in squamous cell carcinomas (5/32, 15.6% versus 3/104, 2.9%, respectively; P = 0.017). Patients with CCs with confirmed HPV-negativity had significantly worse DFS than women with HPV-positive tumours [51.9 months (95% CI 12.2-91.7 months) versus 109.9 months (95% CI 98.2-121.5 months); P = 0.010]. In the multivariate analysis HPV-negativity and International Federation of Gynecology and Obstetrics (FIGO) staging were associated with increased risk of progression and mortality. CONCLUSIONS: An HC2-negative result is an uncommon finding in women with CC, but in almost half of these cases HPVs are identified by more sensitive techniques. CCs with confirmed HPV-negativity are more frequently adenocarcinomas, and seem to be associated with worse DFS.

The increased detection of cervical intraepithelial neoplasia when using a second biopsy at colposcopy.

OBJECTIVE: It has been suggested that colposcopy can miss a significant percentage of high-grade cervical intraepithelial neoplasia (CIN2+). Improved disease ascertainment was evaluated by taking multiple lesion-directed biopsies. METHODS: In a cross-sectional multicenter study in the Netherlands and Spain, 610 women referred to colposcopy following abnormal cervical cytology results were included. Multiple directed biopsies were collected from lesions and ranked according to impression. A non-directed biopsy of normal-appearing tissue was added if fewer than four biopsies were collected. We evaluated the additional CIN2+ yield for one and two directed biopsies. Colposcopic images were reviewed for quality control. RESULTS: In women with at least two lesion-directed biopsies the yield for CIN2+ increased from 51.7% (95%CI; 45.7-57.7) for one directed biopsy to 60.4% (95%CI; 54.4-66.2, p<0.001) for two biopsies. The highest CIN2+ yield was observed in women who were HPV16-positive, had high-grade squamous intraepithelial lesion (HSIL) cytology, and high-grade colposcopy impression. The yield increased from 83.1% (95%CI; 71.5-90.5) with one directed biopsy to 93.2% (95%CI; 83.8-97.3) with two directed biopsies. Only 4.5% additional CIN2+ were detected in biopsies not targeting abnormal areas on the cervix. CONCLUSIONS: A second lesion-directed biopsy is associated with a significant increase in CIN2+ detection. Performing a second lesion-directed biopsy and using a low threshold for abnormality of any acetowhitening should become the standard clinical practice of colposcopy.

Estatura final de una población de prematuros con muy bajo peso al nacer / Final height in a population of preterm infants with very low birth weight

Los niños nacidos prematuros de muy bajo peso, tienen una mayor frecuencia de baja talla a la edad adulta. En la Argentina no contamos con reportes de estatura final de estos niños. Se evaluaron el peso y estatura de 46 jóvenes de la ciudad de Buenos Aires con antecedentes de prematurez y muy bajo peso al nacer egresados de 7 unidades neonatales de la ciudad de Buenos Aires y conurbano bonaerense, entre los años 1990 y 1995. Los 46 jóvenes (27 mujeres) tenían una edad promedio de 18.97 años (16.04 - 22.93). La estatura media de las mujeres fue de -0,71 sDS (0.20) y -0.75 sDS (0.22) en varones. Se detectó baja estatura en 2 mujeres (7.4%) y 1 varón (5.3%). La incidencia global de baja estatura es de 6.5% (AU)

Infants born prematurely with a very low birth weight more often have short stature in adulthood. In Argentina there are no reports on final height in these children. We evaluated weight and height of 46 adolescents and young adults from the city of Buenos Aires with a history of prematurity and very low birth weight who were discharged from seven Departments of Neonatology in the city of Buenos Aires and Greater Buenos Aires between 1990 y 1995. The 46 youth (27 females) had a mean age of 18.97 years (16.04 ­ 22.93). Mean height of the women was -0.71 SDS (0.20) and mean height of the men was -0.75 SDS (0.22). Low stature was observed in two women (7.4%) and one man (5.3%). Overall incidence of short stature was 6.5%. (AU)

The impact of human papillomavirus genotype on colposcopic appearance: a cross-sectional analysis.

OBJECTIVE: To study colposcopic performance in diagnosing high-grade cervical intraepithelial neoplasia or cervical cancer (CIN2+ and CIN3+) using colposcopic characteristics and high-risk human papillomavirus (hrHPV) genotyping. DESIGN: Cross-sectional multicentre study. SETTING: Two colposcopy clinics in The Netherlands and Spain. POPULATION: Six hundred and ten women aged 17 years and older referred for colposcopy because of abnormal cytology. METHODS: A cervical smear was obtained. Colposcopists identified the worst lesion, graded their impression and scored the colposcopic characteristics of the lesions. Up to four biopsies were collected, including one biopsy from visually normal tissue. MAIN OUTCOME MEASURES: CIN2+ and CIN3+, positive for HPV16 or other high-risk HPV types (non-16 hrHPV-positive). RESULTS: The mean age in HPV16-positive CIN2+ women was 35.1 years compared with 39.1 years in women with other hrHPV types (P = 0.002). Sensitivity for colposcopy to detect CIN2+ was 87.9% (95%CI 83.2-91.5), using colposcopic cut-off of 'any abnormality'. The remaining CIN2+ were found by a biopsy from visually normal tissue or endocervical curettage (ECC). Detection of CIN2+ by lesion-targeted biopsies was not different between HPV16-positive women [119/135; 88.1% (95%CI 81.2-92.9)] and non-16 hrHPV-positive women [100/115; 87.0% (95%CI 79.1-92.3); P = 0.776]. In multivariate analysis, 'acetowhitening' [odds ratio (OR) 1.91, 95%CI 1.56-3.17], 'time of appearance' (OR 1.95, 95%CI 1.21-3.15) and 'lesion >25% of visible cervix' (OR 2.25, 95%CI 1.44-3.51) were associated with CIN2+. CONCLUSIONS: In this population following European screening practice, HPV16-related CIN2+ lesions were detected at younger age and showed similar colposcopic impression as non-16 hrHPV high-grade lesions. There was no relationship between any of the colposcopic characteristics and HPV16 status.

Exostosis múltiple: Revisión clínica y radiológica de 45 pacientes en seguimiento en las clínicas de displasias esqueléticas del Hospital Garrahan / Multiple exostoses. Clinical and radiological review of 45 patients followed-up at the unit of clinics of skeletal dysplasias at the Garrahan Hospital

La exostosis múltiple es una enfermedad poco frecuente, autosómica dominante, caracterizada por la presencia de múltiles proyecciones ósas rodeadas de cartílago, producto de un crecimiento anárquico del tejido óseo, ubicadas más frecuentemente en las metáfisis de los huesos largos. La prevalencia estimada de esta condición es 1 en 50000. Los genes supresores de tumores involucrados son EXT1-2 y 3. El objetivo de este estudio fue analizar las características clínicas y radiológicas de los pacientes con exostosis múltiple registrados en la base de datos del servicio de crecimiento y desarrollo desde enero de 1998 a enero de 2008. El número final de la población fue 45, 60% varones, mediana edad a la última consulta 10,6 (r: 3,48 – 17,08) años. Resultados: mediana de edad de la primer exostosis fue 1,88 (r: RN – 12,0) años. Las localizaciones fueron 52% miembros, 19% escápulas, 16% parrilla costal y 13% otras. No diferencias significativas por sexo ni forma de presentación familiar. El 100% de los niños mostró algún hueso largo afectado, 78,3% hueso plano y 30,8% columna. Los síntomas asociados fueron dolor (52%), alteración del eje de miembros superiores (50%) y de miembros inferiores (44,7%), alteración de la función de miembros superiores (38%) y de miembros inferiores (35%). Cinco pacientes presentaron retraso mental. La mayoría de los niños creció debajo del centilo 50. El 50% de los niños requirió alguna cirugía durante su seguimiento. El número de cirugías se asoció a alteración funcional. Un niño presentó asociación de exostosis múltiple con hipocondroplasia. No encontramos antecedentes de malignización. Conclusiones: Las complicaciones observadas en nuestra población fueron semejantes a las descriptas en la literatura siendo el dolor una de las más frecuentes. No encontramos asociación de las mismas con el sexo masculino.

Intraoperative post-conisation human papillomavirus testing for early detection of treatment failure in patients with cervical intraepithelial neoplasia: a pilot study.

OBJECTIVE: To evaluate the feasibility and utility of intraoperative post-conisation human papillomavirus (IOP-HPV) testing and cytology to detect treatment failure in patients with cervical intraepithelial neoplasia grades 2-3 (CIN2-3). DESIGN: Prospective observational pilot study. SETTING: Barcelona, Spain. POPULATION: A cohort of 132 women treated for CIN2-3 by loop electrosurgical conisation. METHODS: An endocervical sample was obtained intraoperatively with a cytobrush from the cervix remaining after the conisation. The material was kept in PreservCyt medium and processed for Hybrid Capture 2 and cytology. Patients were followed-up for 24 months. The performance of IOP-HPV testing and IOP cytology was compared with conventional indicators of recurrence (cone margin, endocervical curettage, and HPV testing and cytology at 6 months). MAIN OUTCOME MEASURE: Treatment failure (i.e. recurrent CIN2-3 during follow-up). RESULTS: Treatment failure was identified in 12 women (9.1%). IOP-HPV testing for sensitivity, specificity, and positive and negative predictive values for treatment failure were 91.7, 78.3, 62.2, and 96.0%, respectively, which are similar to the figures for conventional HPV testing at 6 months (91.7, 76.0, 64.0, and 95.1%, respectively), and are better than the values of other conventional predictive factors (cone margin, endocervical curettage, and cytology intraoperative at 6 months). IOP-HPV was strongly associated with treatment failure in the multivariate analysis (OR 15.40, 95% CI 1.58-150.42). CONCLUSION: IOP-HPV testing is feasible, and accurately predicts treatment failure in patients with CIN2-3. This new approach may allow an early identification of patients with treatment failure, thereby facilitating the scheduling of an attenuated follow-up for negative patients who are at very low risk of persistent disease.