High EPHB2 mutation rate in gastric but not endometrial tumors with microsatellite instability.

The EPH/EFN family of receptor tyrosine kinases regulates cell adhesion and migration and has an important role in controlling cell positioning in the normal intestinal epithelium. Inactivation of EPHB2 has recently been shown to accelerate tumorigenesis in the colon and rectum, and we have previously demonstrated frequent frameshift mutations (41%) in an A9 coding microsatellite repeat in exon 17 of EPHB2 in colorectal tumors with microsatellite instability (MSI). In this study, we extended these analyses to extracolonic MSI cancers, and found frameshift EPHB2 mutations in 39% (25/64) of gastric tumors and 14% (8/56) of endometrial tumors. Regression analysis of these EPHB2 mutation data on the basis of our previously proposed statistical model identified EPHB2 as a selective target of frameshift mutations in MSI gastric cancers but not in MSI endometrial carcinomas. These results suggest a functional role for EPHB2 in gastric tumor progression, and emphasize the differences between the tumorigenic processes in MSI gastrointestinal and endometrial cancer.

Fetal tricuspid regurgitation at the 11 + 0 to 13 + 6-week scan: association with chromosomal defects and reproducibility of the method.

OBJECTIVE: To determine the reproducibility of diagnosing tricuspid regurgitation (TR) at 11 + 0 to 13 + 6 weeks' gestation, to examine further the relationship between TR and the presence of chromosomal defects and to calculate the likelihood ratios for trisomy 21 and trisomy 18 in fetuses with TR. METHODS: Pulsed wave Doppler of flow across the tricuspid valve was carried out by 12 obstetricians, trained in fetal echocardiography, to ascertain the presence or absence of TR in 1557 fetuses at 11 + 0 to 13 + 6 weeks. The assessment was carried out immediately before chorionic villus sampling for fetal karyotyping. In 128 cases, assessment of tricuspid flow was also performed by experienced fetal cardiologists to examine the reproducibility of the method. RESULTS: Tricuspid flow was successfully assessed in 1538 (98.8%) cases and TR was present in 58 (4.4%) of the 1323 chromosomally normal fetuses, 77 (67.5%) of the 114 cases with trisomy 21, and 14 (33.3%) of the 42 cases with trisomy 18. The kappa coefficient of agreement between obstetricians and cardiologists was 0.872 (P < 0.0001). Logistic regression analysis demonstrated that, in chromosomally normal fetuses, significant prediction of the likelihood of TR was provided by delta nuchal translucency (NT). The likelihood ratio for trisomy 21 and trisomy 18 for TR, derived by dividing the likelihood (%) of TR in trisomy 21 by the likelihood (%) in normal fetuses, decreased with delta NT. CONCLUSION: At 11 + 0 to 13 + 6 weeks, TR is a common finding in fetuses with trisomies 21 and 18. Assessment of the tricuspid flow can be performed by sonographers trained in fetal echocardiography.

Screening for trisomy 21 by fetal tricuspid regurgitation, nuchal translucency and maternal serum free beta-hCG and PAPP-A at 11 + 0 to 13 + 6 weeks.

OBJECTIVE: To examine whether in pregnancies with fetal trisomy 21 the level of maternal serum free beta-human chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A) at 11 + 0 to 13 + 6 weeks' gestation is independent of the presence or absence of tricuspid regurgitation and to estimate the performance of a screening test that combines tricuspid regurgitation with fetal nuchal translucency (NT) thickness and serum free beta-hCG and PAPP-A. METHODS: The study population comprised 77 trisomy 21 and 232 chromosomally normal fetuses from singleton pregnancies at 11 + 0 to 13 + 6 weeks of gestation. In all cases the fetal karyotype was determined by chorionic villus sampling (CVS), which was carried out at the request of the parents after first-trimester screening for trisomy 21 by fetal NT and maternal serum free beta-hCG and PAPP-A. Immediately before chorionic villus sampling, fetal echocardiography was performed and the presence or absence of tricuspid regurgitation was determined by pulsed wave Doppler ultrasonography. The distribution of fetal NT, maternal serum free beta-hCG and PAPP-A in trisomy 21 fetuses with absent and present tricuspid regurgitation was examined. We examined two screening strategies: first, integrated first-trimester screening in all patients and second, first-stage screening of all patients using fetal NT and maternal serum free beta-hCG and PAPP-A followed by second-stage assessment of tricuspid regurgitation only in those with an intermediate risk of 1 in 101 to 1 in 1000 after the first stage. RESULTS: Tricuspid regurgitation was observed in 57 (74.0%) of the trisomy 21 fetuses and in 16 (6.9%) of the chromosomally normal fetuses. There were no significant differences in median maternal age, median gestational age, free beta-hCG multiples of the median (MoM) and PAPP-A MoM in trisomy 21 fetuses with and without tricuspid regurgitation. The modeled detection rates of trisomy 21 for fixed false positive rates of 1%, 2% and 5% in screening by maternal age, fetal NT thickness and maternal serum free beta-hCG and PAPP-A and assessment of tricuspid flow in all cases were 87%, 90% and 95%. In the two-stage approach, the estimated detection rate was 91% and the false positive rate was 2.6%. CONCLUSIONS: There is no relationship between tricuspid regurgitation and the levels of maternal serum free beta-hCG and PAPP-A in cases with trisomy 21. An integrated sonographic and biochemical test at 11 + 0 to 13 + 6 weeks can potentially identify about 90% of trisomy 21 fetuses for a false-positive rate of 2-3%.

Lung and heart volumes by three-dimensional ultrasound in normal fetuses at 12-32 weeks' gestation.

OBJECTIVE: To establish reference intervals for the fetal right, left and total lung volumes and heart volume between 12 and 32 weeks of gestation. METHODS: Fetal lung and heart volumes were measured using three-dimensional (3D) ultrasound in 650 normal singleton pregnancies at 12-32 weeks. The VOCAL (Virtual Organ Computer-aided AnaLysis) technique was used to obtain a sequence of six sections of each lung and the heart around a fixed axis, each after a 30 degrees rotation from the previous one. The rotation axis for the lungs extended from the apex to the upper limit of the diaphragm dome, and the rotation axis for the heart extended from its apex to its connection to the great vessels. The contour of each of these organs was drawn manually in the six different rotation planes to obtain the 3D volume measurement. In 60 cases the fetal lungs and heart volumes were measured by the same sonographer twice and also by a second sonographer once in order to compare the measurements and calculate intra- and interobserver agreement. RESULTS: The total lung volume and heart volume increased with gestation, from respective mean values of 1.6 and 0.6 mL at 12 weeks to 10.9 and 4.3 mL at 20 weeks and 49.3 and 26.6 mL at 32 weeks. The right to left lung volume ratio did not change significantly with gestation (median, 0.7), whereas the heart to total lung volume ratio increased with gestation from about 0.3 at 12 weeks to 0.5 at 32 weeks. In the Bland-Altman plot, the difference between paired measurements by two sonographers was, in 95% of the cases, less than 0.05, 0.5 and 1.9 mL for each lung at 12-13, 19-22 and 29-32 weeks, respectively, and the corresponding values for the heart volumes were 0.04, 0.4 and 2.3 mL. CONCLUSIONS: In normal fetuses the lung and heart volumes increase between 12 and 32 weeks of gestation. The extent to which in pathological pregnancies possible deviations in these measurements from normal prove to be useful in the prediction of outcome remains to be determined.

Melanoma vulvar / Vulvar melanoma

El cáncer de vulva es el 5% del total de cánceres ginecológicos y corresponde al 1% de afección maligna femenina. La entidad histológica más frecuente es el cáncer de células escamosas (90-95%). El melanoma representa la segunda enfermedad maligna en frecuencia (8-10%). Se trata de un tumor raro con cierta predisposición por el área vulvar. El melanoma se origina frecuentemente como lesión sobreelevada y pigmentada, localizada en labios menores o clítoris. El pronóstico depende del tamaño y grado de invasión tumoral. La biopsia temprana de cualquier lesión sospechosa es mandatoria. Este trabajo presenta un caso de melanoma vulvar y se expone nuestra experiencia en su manejo clínico, se realiza una revisión actualizada de la bibliografía en relación con su historia natural, distribución por edad, factores epidemiológicos, patología, sistemas de microestadificación para predecir pronóstico, tratamiento y supervivencia

Vulvar cancer accounts for 5% of all female genital cancers and 1% of all malignancies in women. The most common histological type affecting the vulva is squamous cell carcinoma, accounting for approximately 90%-95% of these lesions. Malignant melanoma is the second most common cancer occurring in the vulva, accounting for about 8%-10% of lesions. This uncommon tumor shows a certain predisposition for the vulvar area. Melanomas usually present as raised, pigmented lesions, occurring most commonly on the labia minora or clitoris. Prognosis depends on the size of the lesion and the depth of invasion. Early biopsy of all suspected lesions is mandatory. We present a case of vulvar melanoma and describe our experience in the clinical management of this entity. We also provide a review of the most recent literature on the natural history of this tumor, its distribution among age groups, epidemiological factors, pathology, the microstaging systems used to predict prognosis, treatment, and survival

Fetal head-to-trunk volume ratio in chromosomally abnormal fetuses at 11 + 0 to 13 + 6 weeks of gestation.

OBJECTIVE: To determine the pattern of early growth disturbance in chromosomally abnormal fetuses by comparing the volume of the fetal head to that of the trunk. METHODS: The fetal trunk and head volume was measured using three-dimensional (3D) ultrasound in 145 chromosomally abnormal fetuses at a median gestational age of 12 (range, 11 + 0 to 13 + 6) weeks. The head volume was measured separately and then subtracted from the total head and trunk volume to obtain the volume of the fetal trunk. The head-to-trunk ratios were then calculated and the Mann-Whitney U-test was used to determine the significance of differences from 500 chromosomally normal fetuses. RESULTS: The fetal head volume for crown-rump length (CRL) was significantly smaller than normal in trisomy 21, trisomy 13 and Turner syndrome (P < 0.001, P < 0.001 and P = 0.001, respectively), whereas no significant differences were found in trisomy 18 and triploidy (P = 0.139 and P = 0.070, respectively). The fetal trunk volume for CRL was significantly smaller in all chromosomal abnormalities (P < 0.001) except Turner syndrome (P = 0.134). The head-to-trunk ratio for CRL was significantly larger in trisomy 18, trisomy 13 and triploidy (P < 0.001), but normal in trisomy 21 (P = 0.221) and Turner syndrome (P = 0.768). CONCLUSIONS: In trisomy 21 and Turner syndrome, the growth deficit was symmetrical with the head and trunk being equally affected, whereas in triploidy and trisomies 18 and 13 there was asymmetrical growth restriction with the trunk being more severely compromised than the head.

Fetal trunk and head volume in chromosomally abnormal fetuses at 11+0 to 13+6 weeks of gestation.

OBJECTIVE: To examine the pattern of growth in chromosomally abnormal fetuses at 11+0 to 13+6 weeks of gestation and compare the trunk and head volume to crown-rump length (CRL) in defining the growth deficit in such fetuses. METHODS: The fetal trunk and head volume was measured using three-dimensional (3D) ultrasound in 140 chromosomally abnormal fetuses at 11+0 to 13+6 (median 12) weeks of gestation, and the values were compared to 500 chromosomally normal fetuses. In each chromosomally abnormal fetus, the observed fetal trunk and head volume was subtracted from the expected mean (delta value) of the chromosomally normal fetuses of the same gestational age, and this difference was expressed as a percentage of the appropriate normal mean. The Mann-Whitney U-test was used to determine the significance of differences between the chromosomally normal and abnormal groups. RESULTS: In trisomy 21 (n=72) and Turner syndrome (n=14) fetuses, compared to chromosomally normal fetuses, the CRL for gestation was similar (P=0.335 and P=0.317, respectively), but the fetal trunk and head volume was about 10-15% lower (P<0.001 and P=0.004, respectively). In trisomy 18 (n=29), trisomy 13 (n=14) and triploidy (n=11), the deficit in volume was about 45% (P<0.001), whereas the deficit in CRL was less than 15% (P<0.001). CONCLUSIONS: In the quantification of the degree of early growth impairment in chromosomally abnormal fetuses, measurement of the fetal trunk and head volume using 3D ultrasound may be better than measurement of CRL.

Fetal trunk and head volume measured by three-dimensional ultrasound at 11 + 0 to 13 + 6 weeks of gestation in chromosomally normal pregnancies.

OBJECTIVE: To establish the relationship between fetal trunk and head volume measured by three-dimensional (3D) ultrasound and gestational age at 11 + 0 to 13 + 6 weeks of gestation. METHODS: The fetal trunk and head volume were measured using 3D ultrasound in 417 chromosomally normal fetuses from singleton pregnancies at 11 + 0 to 13 + 6 (median, 12 + 0) weeks of gestation. Regression analysis was used to determine the significance of the association between fetal volume and gestational age. The Bland-Altman analysis was used to compare the measurement agreement and bias for a single examiner and between different examiners. RESULTS: The fetal trunk and head volume increased linearly with gestation from a mean of 5.8 mL at 11 + 0 weeks to 33.3 mL at 13 + 6 weeks and 1 SD was 4.4 mL. There was also a significant linear association between fetal volume and crown-rump length (CRL), from a mean of 5.1 mL at a CRL of 45 mm to 37.5 mL at a CRL of 84 mm and 1 SD was 2.7 mL. However, within this gestational range, a doubling in CRL, from a mean of 48 mm at 11 + 0 weeks to 79 mm at 13 + 6 weeks, was associated with a 5-6-fold increase in fetal volume. The mean difference in fetal volume between paired measurements by the same sonographer was -0.87 mL (95% limits of agreement, -2.31 to 4.05 mL) and the mean difference between paired measurements by two sonographers was -1.09 mL (-5.49 to 3.32 mL). CONCLUSIONS: 3D ultrasound can provide a reproducible measurement of the fetal trunk and head volume in early pregnancy. At between 11 + 0 and 13 + 6 weeks there is a 5-6-fold increase in fetal volume but only a doubling in CRL.

Placental volume measured by three-dimensional ultrasound at 11 to 13 + 6 weeks of gestation: relation to chromosomal defects.

OBJECTIVE: To determine the potential value of measuring the placental volume at 11 to 13 + 6 weeks of gestation in screening for chromosomal defects. METHODS: The placental volume was measured using three-dimensional ultrasound in 500 consecutive singleton pregnancies immediately before chorionic villus sampling for fetal karyotyping at 11 to 13 + 6 (median, 12) weeks of gestation. RESULTS: The fetal karyotype was normal in 417 pregnancies and abnormal in 83. In the chromosomally normal group the mean placental volume increased significantly with gestation from a mean of 51 mL (5th and 95th centiles: 31.2 and 82.4 mL) at 11 weeks to 91 mL (5th and 95th centiles: 55.7 and 147.2 mL) at 13 + 6 weeks. In the chromosomally abnormal group the mean placental volume for gestational age was not significantly different from normal in trisomy 21 and Turner syndrome, but it was smaller in trisomies 13 and 18. CONCLUSIONS: The measurement of the placental volume at 11 to 13 + 6 weeks of gestation is unlikely to be a useful predictor of the major chromosomal defects. In trisomies 13 and 18 the small placental volume may be due to early-onset fetal growth restriction, which could be the consequence of impaired placental function.

Gestational sac volume measured by three-dimensional ultrasound at 11 to 13 + 6 weeks of gestation: relation to chromosomal defects.

OBJECTIVE: To determine the potential value of measuring the gestational sac volume (GSV) at 11 to 13 + 6 weeks of gestation in screening for chromosomal defects. METHODS: The GSV was measured using three-dimensional (3D) ultrasound in 500 consecutive singleton pregnancies immediately before chorionic villus sampling (CVS) for fetal karyotyping at 11 to 13 + 6 (median 12) weeks of gestation. RESULTS: The fetal karyotype was normal in 417 pregnancies and abnormal in 83. In the chromosomally normal group, the mean GSV increased significantly with gestational age from a mean of 69 mL at 11 weeks to 144 mL at 13 + 6 weeks (the standard deviation was 27 mL). In the chromosomally abnormal group, the mean GSV for gestational age was not significantly different from normal in fetuses with trisomy 21, trisomy 18 and Turner syndrome, but it was smaller in those with triploidy and trisomy 13. However, the mean GSV for crown-rump length (CRL) was significantly larger in trisomy 18, smaller in triploidy and trisomy 13, and not different from normal in trisomy 21 and Turner syndrome. The mean CRL for gestational age was significantly smaller than normal in trisomy 18, triploidy and trisomy 13. CONCLUSIONS: The measurement of the GSV at 11 to 13 + 6 weeks of gestation is unlikely to provide useful prediction of the major chromosomal defects. In trisomy 13 and triploidy, the small GSV may be due to early onset fetal growth restriction and reduced amniotic fluid volume. In trisomy 18, the increase in GSV is probably due to the presence of associated fetal abnormalities that interfere with fetal swallowing.

Cáncer invasivo de cérvix en España (1995). Encuesta de la Sociedad Española de Ginecología y Obstetricia / Invasive cervical cancer in Spain (1995). Survey of the Spanish Society of Obstetrics and Gynecology

Objetivos: Conocer la atención al cáncer de cérvix en España mediante una encuesta retrospectiva sobre casos de 1995 realizada por la Sección de Ginecología Oncológica y Patología Mamaria de la SEGO. Sujetos y métodos: Contestaron a la encuesta 45 hospitales que informaron de 633 casos. El número de casos por hospital osciló entre 1 y 40, siendo la mediana de 11. Pudieron procesarse 578 fichas. Resultados: La edad media de las pacientes fue de 51,2 años. El 49,3% de los casos se diagnosticó en estadio I; el 27,5% en estadio II; el 16,2% en estadio III, y el 4,6% en estadio IV. El tratamiento más empleado fue quirúrgico, mediante la intervención de Wertheim. La supervivencia a los 5 años fue del 56,4%. Conclusiones: Los factores pronósticos identificados en la evolución del cáncer de cérvix fueron el estado ganglionar, la invasión parametrial, la afección del espacio linfovascular y el tipo histológico

Objectives: To ascertain the diagnosis, treatment and outcomes of cervical carcinomas in Spain through a retrospective survey of cases diagnosed in 1995 carried out by the Oncological Gynecology and Breast Disease Section of the Spanish Society of Obstetrics and Gynecology (SEGO). Subjects and methods: Forty-five hospitals responded, providing information on 633 patients with cervical carcinoma diagnosed in 1995. The number of cases per hospital ranged between one and 40, with a median of 11. A total of 578 forms were included. Results: The mean age at diagnosis was 51.2 years. A total of 49.3% of carcinomas were in stage I, 27.5% were in stage II, 16.2% were in stage III, and 4.6% were in stage IV. The most commonly used treatment was surgery (Wertheim’s intervention). Gross 5-year survival was 56.4%. Conclusions: The prognostic factors identified were affected lymph nodes, parametrial and lymphovascular invasion, and histological subtypes

Assessment of the gap between the fetal nasal bones at 11 to 13 + 6 weeks of gestation by three-dimensional ultrasound.

OBJECTIVE: To detect the presence of a gap between the fetal nasal bones at 11 to 13 + 6 weeks of gestation and to verify if this gap could lead to the erroneous diagnosis of absent nasal bone. METHODS: Three-dimensional (3D) ultrasound was used to assess the fetal nose in 450 singleton pregnancies, immediately after two-dimensional (2D) evaluation of the nasal bones and screening for chromosomal defects by a combination of maternal age and the measurement of fetal nuchal translucency at 11 to 13 + 6 (median, 12) weeks of gestation. A 3D volume of the fetal face was acquired and then analyzed using the multiplanar mode. A sequence of transverse views was used to confirm the presence or absence of the nasal bones and when they were present any visible gap between them was measured. A perfectly mid-sagittal plane was then examined to determine if the nasal bone was visible or not. RESULTS: In 421/450 (93.6%) cases the nasal bone was present during 2D ultrasound. Using the multiplanar mode of 3D ultrasound, in 83/421 (19.7%) fetuses a gap between the nasal bones could be demonstrated and in 36/83 (43.4%) cases the nasal bone was found to be absent in the perfect mid-sagittal view. In 29/450 (6.4%) cases the nasal bones were absent during the 2D scan. In the 3D assessment there was absence of both bones in 25/29 (86.2%) cases and absence of one of the two bones in 4/29 (13.8%) cases. Chorionic villus sampling demonstrated that the fetal karyotype was normal in 404 and abnormal in 46 cases, including 31 cases of trisomy 21. There was absence of one or both nasal bones in three (0.7%) of the chromosomally normal fetuses, in 19 (61.3%) with trisomy 21 and in seven (46.7%) with other chromosomal defects. CONCLUSIONS: At 11 to 13 + 6 weeks of gestation there is a gap between the nasal bones in about 20% of fetuses, and in about 40% of these cases in the perfect mid-sagittal plane the nasal bone may erroneously be considered to be absent.

Multicenter study of first-trimester screening for trisomy 21 in 75 821 pregnancies: results and estimation of the potential impact of individual risk-orientated two-stage first-trimester screening.

OBJECTIVES: To evaluate the performance of first-trimester screening for trisomy 21 by a combination of maternal age, fetal nuchal translucency (NT) and maternal serum free beta-human chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A). In addition, the potential impact of a new individual risk-orientated two-stage approach to first-trimester screening was examined. METHODS: First-trimester combined screening for trisomy 21 was carried out in 75 821 singleton pregnancies with live fetuses at 11 + 0 to 13 + 6 gestational weeks. The detection and false-positive rates for different risk cut-offs were calculated. To examine the potential impact of an individual risk-orientated two-stage approach to first-trimester screening it was assumed that, after first-trimester combined screening, chorionic villus sampling (CVS) would be performed in all patients with a risk estimate of 1 in 100 or more and in none of those with a risk estimate of less than 1 in 1000. Those in the intermediate-risk category, with a risk estimate of between 1 in 101 and 1 in 1000, would have further assessment of risk by first-trimester ultrasound examination to determine presence/absence of the nasal bone, presence/absence of tricuspid regurgitation or normal/abnormal Doppler velocity waveform in the ductus venosus, and CVS would be performed if their adjusted risk became 1 in 100 or more. RESULTS: Fetal NT and maternal serum free beta-hCG and PAPP-A were successfully measured in all cases. The median maternal age was 31 (range, 13-49) years, the median gestation at screening was 12 (range, 11 + 0 to 13 + 6) weeks and the median fetal crown-rump length was 62 (range, 45-84) mm. Chromosomal abnormalities were identified in 544 pregnancies, including 325 cases of trisomy 21. The estimated risk for trisomy 21 was 1 in 300 or greater in 5.2% of normal pregnancies, in 92.6% of those with trisomy 21, in 88.5% of those with trisomy 18 or 13 and in 85.6% of those with other chromosomal defects. The detection rates for trisomy 21 were about 75% and 80% for respective false-positive rates of 1% and 2%. In the proposed individual risk-orientated two-stage screening for a risk cut-off of 1 in 100 the total false-positive rate would vary with the method used for the second stage of screening from 2.1% for absence of the nasal bone to 2.7% for increased impedance in the ductus venosus and 2.7% for tricuspid regurgitation and the respective detection rates would be 92.0%, 94.2% and 91.7%. CONCLUSIONS: First-trimester combined screening for trisomy 21 is associated with a detection rate of about 90% for a false-positive rate of 5%. Individual risk-orientated two-stage screening for trisomy 21 can potentially identify, in the first trimester of pregnancy, more than 90% of affected fetuses for a false-positive rate of 2-3%.

Miocardiopatía periparto como causa de insuficiencia cardíaca durante la gestación / Peripartum cardiomyopathy as a cause of heart failure during pregnancy

La miocardiopatía periparto es una rara forma de insuficiencia cardíaca que afecta a mujeres durante el embarazo tardío o puerperio, con consecuencias potencialmente letales. El cuadro clínico es el de una insuficiencia cardíaca congestiva, que a veces se puede pasar por alto debido a que puede tener síntomas similares a los de un embarazo normal, como la disnea. El tratamiento es similar al empleado en otros tipos de disfunción ventricular izquierda; sin embargo, a veces se requieren modificaciones del tratamiento estándar para seguridad de la madre y del feto o lactante. Salvo pocas excepciones, el parto vaginal con la abreviación del período expulsivo mediante fórceps es preferible en mujeres con enfermedad cardíaca, y un control hemodinámico exhaustivo de la paciente durante el puerperio inmediato es de extrema importancia. La mortalidad de este proceso se encuentra en torno al 30-40 por ciento, casi siempre durante los 3 primeros meses posparto, aunque alrededor del 50 por ciento de las pacientes tiene una marcada mejoría de la función ventricular (AU)

Carcinoma epidermoide de cérvix tratado con radioterapia radical: factores clásicos de pronóstico y resultados / Epidermoid carcinoma of the cervic treated with radical radiotherapy: classical prognostic factors and results

Objetivo: El estudio en una serie homogénea de pacientes, de la influencia de factores clásicos de pronóstico (edad, estadio clínico, tamaño tumoral, grado histológico, afectación ganglionar) en relación con la respuesta, control local y supervivencia, nos permitirá la identificación de factores que deberían ser controlados en el diseño de futuros estudios.Sujetos y métodos: Se han incluido entre diciembre de 1977 y abril de 1999 204 pacientes diagnosticadas de carcinoma epidermoide de cérvix y tratadas con RT radical. Cincuenta y cuatro pacientes (26 por ciento) eran estadio Ib, 112 (55 por ciento) estadio II y 38 (19 por ciento) estadio III. El tamaño medio tumoral fue 4,11 cm (1-9). La mayoría presentaban tumores grado II (43 por ciento) o III (45 por ciento). En 152 pacientes se evaluó la afectación ganglionar mediante TAC, que estuvo presente en 20 casos (13 por ciento). Resultados: El tamaño tumoral se relacionó directamente con el estadio (p < 0,015), y de forma inversa con la edad (p < 0,0001). Se observó diferencia significativa en la afectación ganglionar entre los estadios I vs II-III (p < 0,02). Ciento cincuenta y tres pacientes tuvieron respuesta completa (75 por ciento). El control local fue del 74, 67 y 65 por ciento a 1, 5 y 10 años, respectivamente. Tanto la respuesta como el control local se relacionaron estrechamente con el estadio y el tamaño tumoral en el análisis multivariante (AM). La supervivencia causa-específica fue del 85, 67 y 62 por ciento a 1, 5 y 10 años, respectivamente. La respuesta fue el principal factor predictivo de supervivencia en el AM seguida del estadio.Conclusiones: La extensión de la enfermedad (estadio clínico, tamaño tumoral) es el factor predictivo más relevante de respuesta completa, y ésta a su vez es el principal factor pronóstico de supervivencia por su impacto en la esfera local del proceso. Sin embargo, pacientes con idéntica extensión y volumen de la enfermedad muestran evoluciones diferentes, por lo que la importancia de otras características biológicas tumorales en la respuesta a RT y en la supervivencia será motivo de estudios posteriores (AU)

Low levels of cathepsin D are associated with a poor prognosis in endometrial cancer.

Total cytosolic cathepsin D (Cat D) levels were estimated by an immunoradiometric assay in a series of 156 consecutive patients with surgical stages I-III primary endometrial adenocarcinoma. Simultaneously, the tissue content of both oestrogen (ER) and progesterone (PR) receptors, and p185HER-2/neu, DNA content (ploidy), and the fraction of S-phase cells (S-phase) were also estimated. Tumoral Cat D content ranged from 0 to 243 pmol mg(-1) protein (median 44 pmol mg(-1) protein) and was not associated with any of the established clinicopathological and biological prognostic variables, with the exception of a weak positive correlation with the tumoral p185HER-2/neu levels. Univariable analysis performed on a subset of 97 patients, followed for a minimum of 2 years or until death, showed that patient age at diagnosis, high histological grade, advanced surgical stage, vascular invasion, positive peritoneal cytology, low levels of Cat D, negative ER and PR status, aneuploidy, and high S-phase were predictive of the presence of persistent or recurrent disease. However, multivariable analysis revealed that only histological grade, surgical stage, Cat D and PR were significantly associated with the patient's outcome. From these findings, we conclude that Cat D is an independent prognostic factor in endometrial adenocarcinoma, its low levels being associated with a worse clinical outcome.

Quantitative analysis of p185(HER-2/neu) protein in breast cancer and its association with other prognostic factors.

The total cellular p185(HER-2/neu) protein (p185) content was measured by ELISA in 346 invasive primary breast cancers, and the results were compared with those of estrogen (ER) and progesterone (PR) receptors, pS2 and Cathepsin D (Cat D) content. At a cut-off level of 260 fmol/mg protein, 53 of the 346 tumors (15%) were p185-positive. A significant positive correlation was observed between p185 levels and those of Cat D, and a weaker, though significant, positive correlation with ER, and pS2 levels, but not with those of PR. However, when only the 293 p185-negative tumors were considered, the correlation between p185 and ER improved substantially, and statistical significance was reached for PR. p185-positive tumors exhibited lower ER and PR content and higher Cat D content than p185-negative tumors. The pS2 content, in contrast, did not undergo significant variation. Tumors considered to be p185-positive were significantly more frequently positive for Cat D at the cut-off of 45 pmol/mg protein, and were more frequently negative for ER and/or PR, but only significant at the cut-off of 15 fmol/mg or higher for both steroid receptors. Finally, p185 status was not associated with menopausal status, tumor size, axillary-lymph-node invasiveness or distant metastases. These results suggest that 260 fmol/mg protein as the cut-off for p185 allows the identification of a tumoral sub-population with a more aggresive phenotype.

Gunshot wounds traversing the mediastinum: guidelines for evaluation and management.

When there is suspicion that a penetrating would to the chest has crossed the midline, it is incumbent upon the medical staff to actively exclude injuries to mediastinal structures such as the heart, aortic arch, bronchial tree, and esophagus, even though injury to such structures may not be immediately clinically apparent. The successful management of a patient with a gunshot wound apparently traversing the anterior mediastinum is presented; an esophagram identified an unsuspected through-and-through injury to the esophagus. The evaluation of this patient is discussed, and an algorithm for the evaluation and management of similar patients is proposed.

Endometrial stromal sarcoma expression of estrogen receptors, progesterone receptors and estrogen-induced srp27 (24K) suggests hormone responsiveness.

The endometrial stroma plays a decisive role in sustaining the gland epithelium along the menstrual cycle, and in preparing the microenvironment that allows embryo implantation. The stroma undergoes important changes during the menstrual cycle that affects both the cell number and differentiation. These changes are regulated by both estrogen and progesterone. Stromal sarcomas are extremely rare, occurring much less than any other uterine tumor. Their origin and biology are poorly understood. The purpose of this work was to try to learn more about the stromal physiology, and also to ascertain whether the stromal sarcoma has characteristics of hormone dependence. We studied the presence of estrogen receptors (ER), progesterone receptors (PR) and the stress-responsive protein of 27K (srp27, a protein first described as an estrogen-induced 24K protein in MCF-7 cells) in both normal stroma and stromal sarcoma. The ER and PR were measured by exchange assays. The srp 27 was studied both by Western-blot and by IHC by means of specific monoclonal antibodies. The stromal sarcomas studied showed a high concentration of both ER (96 to 116 fmol/mg prot.) and PR (565 to 995 fmol/mg prot.). These amounts of ER and PR were higher than the mean found in normal endometrium during the proliferative phase (43 and 637 fmol/mg prot., respectively), and much higher than that of the secretory phase (17 and 229 fmol/mg prot., respectively). The srp27 characterized by Western-blot in both the normal stroma and stromal sarcoma was found to be similar to the srp27 of breast cancer. The IHC results showed a very low expression of srp27 in the stroma during the proliferative phase that increases when the endometrium enters the secretory phase. The low-malignancy grade stromal sarcomas showed abundant expression of srp27, but the high-malignancy grade sarcomas showed no expression of srp27. The obtained results prove the stroma capability to express the srp27. A negative correlation between malignancy of stromal tumors and srp27 expression was found. The presence of ER and PR in some stromal sarcomas proves that they have characteristics of hormone responsiveness. These findings suggest that ER and PR assays should be routinely performed in stromal sarcomas as well as in endometrial adenocarcinomas, and also that antiestrogenic drugs might be considered for the treatment of ER and PR positive stromal sarcomas.