Correlation between late gadolinium enhancement sequences in MRI and pathologic response after neoadjuvant chemotherapy in breast cancer / Correlación entre secuencias de realce tardío de gadolinio en RM y respuesta patológica tras quimioterapia neoadyuvante en cáncer de mama

Objectives: To study the correlation between radiologic response observed by late enhancement sequences in MRI and pathologic response after neoadjuvant chemotherapy in patients with breast cancer. Material and methods: Retrospective observational study of 132 patients with 136 tumors (4 with bilateral disease), treated consecutively with neoadjuvant chemotherapy at our institution between 2011 and 2017. In all cases, we performed 3 breast MRI's, using late enhancement gadolinium sequences: the first prior to neoadjuvant chemotherapy, the second half way through treatment, and the third at the completion of therapy. Following treatment, contrast medium uptake in tumor bed was evaluated based on the Response Evaluation Criteria for Solid Tumors (RECIST). All patients underwent conservative or radical surgery. We compared the radiologic response estimated by MRI, with the pathologic response observed in the surgical specimen, according to Miller and Payne grading system. We calculated the sensitivity, specificity, and predictive values of the test, and used the Spearman correlation coefficient to stablish correlations between the parameters analyzed. Results: Complete pathologic response (pCR) was observed in 58.1% (79/136). The percentage of global radio-pathologic correlation was 88.97%. MRI showed a sensitivity of 78.9%, a specificity of 79.7%, a positive-predictive value (PPV) of 73.8% and a negative-predictive value (NPV) of 84%. In patients with partial response, the Spearman correlation was positive (rho = 1, P < .001). According to surrogate subtypes of breast cancer, we observed moderate correlation for luminal tumors (rho = 0.63, P < .001) and poor correlation for non-luminal types (rho = 0,4, P < .01). (AU)

Objetivos: Estudiar la correlación entre la respuesta radiológica observada mediante secuencias de realce tardío en resonancia magnética y la respuesta patológica después de quimioterapia neoadyuvante en pacientes con cáncer de mama. Material y métodos: Estudio observacional retrospectivo de 132 pacientes con 136 tumores (cuatro con enfermedad bilateral), tratados consecutivamente con quimioterapia neoadyuvante en nuestra Institución entre 2011 y 2017. En todos los casos se realizaron tres resonancias magnéticas de mama, utilizando secuencias de realce tardío de gadolinio: la primera antes de la quimioterapia neoadyuvante, la segunda a mitad del tratamiento y la tercera al finalizar la terapia. Después del tratamiento, la captación media de contraste en el lecho tumoral se evaluó en función de los Criterios de Evaluación de la Respuesta para Tumores Sólidos (RECIST). Todas las pacientes se sometieron a cirugía conservadora o radical. Comparamos la respuesta radiológica estimada por resonancia magnética, con la respuesta patológica observada en la pieza quirúrgica, valorada según clasificación de Miller y Payne. Se calcularon sensibilidad, especificidad, valores predictivos y correlacion de Spearman para establecer correlaciones entre los parametros analizados. Resultados: Se observó respuesta patológica completa (pCR) en el 58,1% (79/136). El porcentaje de correlación radiopatológica global fue del 88,97%. La RM mostró una sensibilidad del 78,9%, una especificidad del 79,7%, un valor predictivo positivo (VPP) del 73,8% y un valor predictivo negativo (VAN) del 84%. En pacientes con respuesta parcial, la correlación de Spearman fue positiva (rho = 1, p < 0,001). De acuerdo con los tipos subrogados de cáncer de mama, observamos una correlación moderada para los tumores luminales (rho = 0,63, p < 0,001) y una correlación deficiente para los tipos no luminales (rho = 0,4, p < 0,01). (AU)

Biopsia selectiva de ganglio centinela tras quimioterapia neoadyuvante en pacientes con axila negativa al inicio / Sentinel lymph node biopsy after neoadjuvant chemotherapy in patients with negative axillary involvement at initial diagnosis

OBJETIVO: valorar la tasa de detección de ganglio centinela tras quimioterapia neoadyuvante en pacientes con cáncer infiltrante de mama y axila clínicamente negativa previa al tratamiento y analizar su supervivencia global y supervivencia libre de enfermedad. MATERIAL Y MÉTODOS: estudio observacional retrospectivo. Se incluyeron las pacientes con cáncer de mama tratadas con quimioterapia neoadyuvante en el Hospital Universitario Quironsalud Madrid entre los años 2008-2014. A todas se les practicó cirugía conservadora o radical junto con biopsia selectiva de ganglio centinela posneoadyuvancia. Se recogió información correspondiente a características sociodemográficas, variables relacionadas con el tratamiento quirúrgico y médico, evolución, características del tumor, supervivencia global y supervivencia libre de enfermedad. RESULTADOS: se incluyeron en el estudio 112 pacientes (116 tumores, 4 de ellos bilaterales). De los 112 tumores unilaterales, 98 (84,5%) estaban en estadios iniciales. La mediana de tamaño tumoral fue 20 mm (15-30). La práctica totalidad (97,4%) eran carcinomas ductales infiltrantes. La quimioterapia se basó en antraciclinas y taxanos con adición de carboplatino en los casos triple negativo y de trastuzumab en Her-2/neu sobreexpresado. Se realizó cirugía conservadora en el 59,5%. La tasa de detección de ganglio centinela fue del 100% con un valor predictivo negativo del 99,1% (110/111), al encontrar una sola recidiva axilar en los 111 ganglios centinela negativos, y se obtuvo respuesta completa patológica en el 52,6%, mayoritariamente en los tumores Her-2 puros y triples negativos con diferencia estadísticamente significativa (p:0.018). La supervivencia global fue del 99,1% con mediana de seguimiento de 53 meses, observando eventos de recaída en 10 pacientes de las cuales solo 2 fueron axilares. CONCLUSIONES: en nuestra experiencia, la biopsia selectiva de ganglio centinela sistemática posneoadyuvancia en pacientes con axila negativa al inicio presenta una excelente tasa de detección, sin aumentar el número de recidivas axilares de forma significativa ni la supervivencia global de estas pacientes. Consideramos, por tanto, esta estrategia la mejor opción para la estadificación quirúrgica de estos tumores

OBJECTIVE: To assess sentinel lymph node biopsy rate after neoadjuvant chemotherapy in breast cancer patients with negative axillary nodes at diagnosis and to analize their disease free interval and overall survival. MATERIAL AND METHODS: Retrospective observational study including breast cancer patients with neoadjuvant chemotherapy at the Hospital Universitario Quironsalud Madrid between 2008-2014. Post chemotherapy, all patients underwent conservative or radical surgery along with a systematic sentinel lymph node biopsy. Patients data was collected and included sociodemographic characteristics, variables regarding surgical and medical treatment, follow-up, tumor characteristics, overall and disease-free survival. RESULTS: The study included 112 patients (116 tumors, 4 of them bilateral). Of the 112 unilateral tumors, 98 (84.5%) were early stages. The median tumor size was 20 mm (15-30) and the majority (97,4%) were invasive ductal carcinoma chemotherapy was based on anthracyclines and taxanes with addition of carboplatin in triple negative cases and trastuzumab in Her-2/neu positive tumors. Conservative procedures were performed in 59,5% of cases. Sentinel lymph node detection rate reached 100% with a negative predictive value of 99,1% (110/111) finding only one axillary recurrence among 111 SLNB. We achieved pathological complete response in 52,6% of tumors in the breast, and more specifically in pure Her2/neu positive and triple negative surrogates (p:0.018). Overall survival was 99,1% with median follow-up of 53 months and 10 patients had a relapse, with only two patients with axillary involvement. CONCLUSIONS: In our experience, sentinel lymph node biopsy performed systematically after neoadjuvant treatment in clinically node negative patients have an excellent detection rate without increasing the axillary recurrence rate nor decreasing overall survival in this group of patients. We consider this strategy the best option for the surgical staging of this tumors after chemotherapy

Diffusion-weighted magnetic resonance imaging evaluation of intra-abdominal sites of implants to predict likelihood of suboptimal cytoreductive surgery in patients with ovarian carcinoma.

OBJECTIVES: To analyse the diagnostic accuracy and to establish a predictive score based on diffusion-weighted magnetic resonance imaging (DWMRI) compared to exploratory laparotomy (EL) for predicting suboptimal cytoreductive surgery for different intra-abdominal sites of implants in patients with ovarian cancer. METHODS: Thirty-four patients with advanced ovarian carcinoma were studied. Preoperative DWMRI of the abdomen and pelvis was performed. DWMRI findings were compared with EL. Ten anatomical sites were selected for inclusion in the score. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy for suboptimal cytoreduction were calculated for both DWMRI and EL. Receiver operating characteristic (ROC) curve analysis was used to assess the ability to predict suboptimal cytoreduction. RESULTS: Using predictive score, ROC curves were generated with an area under the curve of 0.938 for DWMRI and 0.947 for EL (P < 0.0001). For DWMRI, a score ≥6 had the highest overall accuracy at 91.1 % and identified patients with unnecessary EL with a sensitivity of 75 %. For EL, a score ≥4 had the highest overall accuracy at 88.2 % and was able to identify patients with unnecessary EL with a sensitivity of 87.5 %. CONCLUSIONS: DWMRI is an emerging technique that may be useful to predict suboptimal cytoreduction in ovarian cancer. KEY POINTS: • DWMRI is increasingly used in ovarian cancer. • DWMRI is an accurate technique for depicting intra-abdominal sites of implants • DWMRI is useful for predicting optimal cytoreductive surgical outcome. • We report a high predictive value similar to exploratory laparotomy.

Aurora kinases as prognostic biomarkers in ovarian carcinoma.

We investigated the expression of Aurora kinases A and B by immunohistochemistry in 68 ovarian carcinomas to analyze their prognostic value. The amplification of AURKA gene by fluorescence in situ hybridization was also assessed. Overall, 58.8% and 85.3% of ovarian carcinomas showed expression of Aurora A and B, respectively. Amplification of AURKA was found in 27.6% of cases examined. Tumors with Aurora A expression showed a lower rate of recurrence than those tumors without Aurora A expression (65% versus 91.7%, P = .019). In the univariate analysis, patients with Aurora A and B expression showed an increased progression-free survival (P = .023 and .06, respectively, log-rank test) and overall survival (P = .03 and .02, respectively, log-rank test). The multivariate analysis adjusted to optimal surgery by Cox proportional hazards regression showed Aurora A expression as an independent prognostic factor for progression-free survival (P = .03) and overall survival (P = .02). In conclusion, Aurora A expression seems to have a prognostic value in ovarian carcinoma.

Hormonoterapia como primer tratamiento en pacientes no subsidiarias de cirugía en cáncer de mama / Hormonotherapy as the first therapeutic option in non-surgical breast cancer patients

Objetivos: Valorar la respuesta y la supervivencia utilizando tratamiento hormonoterápico en pacientes con cáncer de mama no subsidiarias de cirugía. Material y métodos: Estudio retrospectivo de 153 pacientes con carcinoma de mama no operable por enfermedad extensa, edad avanzada, comorbilidad grave o rechazo a la terapia convencional, tratadas con hormonoterapia. Valoramos el estadio inicial, la respuesta, la supervivencia global y hasta el primer evento así como causas de fallecimiento. Resultados: La edad media ± desviación estándar fue 79 ± 7 años y el seguimiento medio 42,6 meses (0-180 meses). Al diagnóstico, 22% presentaba T4; el 47%, afectación ganglionar clínica, y el 16%, enfermedad metastásica. El 87,7% recibió tamoxifeno y el resto, inhibidores de aromatasa o megestrol. El 22% tuvo otros tratamientos sucesivos. El 5,8% presentó respuesta completa; el 31,8%, parcial; el 34,4%, estabilización, y el 9,7%, progresión. El primer evento apareció a 35,7 ± 33 meses de seguimiento. La mortalidad global a 5 años fue del 68,6% y la mortalidad debida a cáncer de mama del 57,3%. Conclusiones: La hormonoterapia puede plantearse como primera opción en estas pacientes al ser eficaz con escasos efectos secundarios

Objectives: To analyze the response to hormonotherapy and survival in non-surgical breast cancer patients. Material and methods: We performed a retrospective study of 153 patients with inoperable breast carcinoma due to advanced disease, advanced age, severe comorbidity or refusal to accept conventional therapy, who were treated with hormonotherapy. Initial tumoral stage, response, overall survival and causes of death were evaluated. Results: The mean age was 79 ± 7 years with a mean follow-up of 42.6 months (range: 0-180). At diagnosis, stage T4 tumors were found in 22%, clinical nodal involvement was found in 47% and metastasis in 16%. Tamoxifen was administered in 87.7% of the patients and aromatase inhibitors or megestrol in the remainder. Successive treatments were required in 22%. Complete response occurred in 5.8% and partial response in 31.8%. Of there maining patients, 34.4% remained stable and 9.7% showed disease progression. The first event occurred at 35.7 ± 33 months of follow-up. Overall mortality was 68.7% and breast cancer mortality was 57.3%. Conclusions: Because of its efficacy and scarce adverse effects, hormonotherapy may be an effective treatment in non-surgical patients with breast carcinoma

Angiogenesis-related gene expression profile with independent prognostic value in advanced ovarian carcinoma.

BACKGROUND: Ovarian carcinoma is the most important cause of gynecological cancer-related mortality in Western societies. Despite the improved median overall survival in patients receiving chemotherapy regimens such as paclitaxel and carboplatin combination, relapse still occurs in most advanced diseased patients. Increased angiogenesis is associated with rapid recurrence and decreased survival in ovarian cancer. This study was planned to identify an angiogenesis-related gene expression profile with prognostic value in advanced ovarian carcinoma patients. METHODOLOGY/PRINCIPAL FINDINGS: RNAs were collected from formalin-fixed paraffin-embedded samples of 61 patients with III/IV FIGO stage ovarian cancer who underwent surgical cytoreduction and received a carboplatin plus paclitaxel regimen. Expression levels of 82 angiogenesis related genes were measured by quantitative real-time polymerase chain reaction using TaqMan low-density arrays. A 34-gene-profile which was able to predict the overall survival of ovarian carcinoma patients was identified. After a leave-one-out cross validation, the profile distinguished two groups of patients with different outcomes. Median overall survival and progression-free survival for the high risk group was 28.3 and 15.0 months, respectively, and was not reached by patients in the low risk group at the end of follow-up. Moreover, the profile maintained an independent prognostic value in the multivariate analysis. The hazard ratio for death was 2.3 (95% CI, 1.5 to 3.2; p<0.001). CONCLUSIONS/SIGNIFICANCE: It is possible to generate a prognostic model for advanced ovarian carcinoma based on angiogenesis-related genes using formalin-fixed paraffin-embedded samples. The present results are consistent with the increasing weight of angiogenesis genes in the prognosis of ovarian carcinoma.

Mastitis granulomatosa lobulillar idiopática / Idiopathic granulomatous lobular mastitis

Presentamos un caso de mastitis granulomatosa lobulillar idiopática, entidad benigna infrecuente de la mama, que es importante tener en cuenta en el diagnóstico diferencial de los nódulos mamarios por su posible confusión con un proceso neoplásico maligno. El diagnóstico pasa por la escisión quirúrgica y el análisis anatomopatológico de la pieza de biopsia. La actitud terapéutica puede ser diversa

We present a case of idiopathic granulomatous lobular mastitis, which is a rare benign disease of the breast. This entity should be taken into account in patients with a breast lump, because it can mimic carcinoma of the breast. Tissue biopsy is the gold standard to confirm the diagnosis, while various options are available for treatment

Immediate breast reconstruction (IBR) with direct, anatomic, extra-projection prosthesis: 102 cases.

There are different methods described until now for immediate breast reconstruction. Despite the use of autologous flaps considered by many authors, implants are considered as an option by others. A prospective study of 102 clinical cases was designed, including a 1-year follow-up in which glands were reconstructed by immediate breast reconstruction (IBR) with direct, extra projection, anatomic prostheses located in a submuscular pocket after a skin-sparing mastectomy. The prosthesis coverage was made by the muscle in its upper two thirds and by using the skin from the mastectomy in its lower third. The cosmetic results obtained were evaluated according to the volume, form, and symmetry achieved using a linear numeric analogical score. This evaluation had an averaged value of 2.79 +/- 0.8 in our scale from poor (0) to excellent result (4). The overall rate of complications was 15.7% of the cases, with seroma being the most frequent. In conclusion, this preliminary study demonstrates that immediate breast reconstruction with a direct, extra projection, anatomic prosthesis is a good alternative. Nevertheless, more long-term studies with a higher number of patients and using an SF-36 for patient satisfaction are needed to confirm these results.

Rotura espontánea de útero bicorne en gestación asociada a acretismo placentario / Spontaneous uterine rupture in a bicornuate uterus associated with placenta accreta

La rotura espontánea en útero bicorne gestante es un accidente poco frecuente y difícil de diagnosticar. La prevalencia de malformaciones uterinas congénitas entre las mujeres fértiles está documentada entre 1-2 por ciento de la población; de éstas, el útero bicorne varía entre un 25 a 37 por ciento. Generalmente la rotura de la pared uterina sucede en el segundo trimestre, presentándose como intenso dolor abdominal a consecuencia de la hemorragia intraperitoneal. Presentamos caso clínico de una paciente gestante de 19 semanas con útero bicorne en el que se produjo una rotura uterina asociada a acretismo placentario. La placenta acreta y el útero bicorne son 2 entidades muy poco frecuentes pero que pueden asociarse. Como tratamiento se realizó una hemihisterectomía izquierda con una evolución satisfactoria.

The sudden rupture in bicornuate pregnant uterus is an uncommon and difficult-to-diagnose occurrence. The prevalence of congenital uterine malformations amongst fertile women is documented for 1-2 percent of the population; of these, bicornuate uterus varies from 25 to 37 percent. The rupture of the uterine wall happens generally in the second trimester, accompanied by an intense abdominal pain as a result of the intraperitoneal hemorrhage. We report a case of a 19 weeks pregnancy with an uterine rupture in a bicornuate uterus associated with a placental accretism. Both placental accretism and bicornuate uterus are uncommon but can be related. A left-side hemihysterectomy was applied leading to a satisfactory evolution.

Expression of cadherins and catenins correlates with distinct histologic types of ovarian carcinomas.

Alterations in the cadherin-catenin expression and activation of the Wnt signaling have been related to the pathology of ovarian carcinomas. Here, we evaluated the immunoreactivity of cadherins (E-, P-, and N-cadherin and cadherin-11) and catenins (alpha-, beta-, and gamma-catenin and p120) in 86 ovarian tumors. We found significant differences in the expression of all cadherins and catenins among the distinct histologic tumor types. Clear cell tumors were rarely N-cadherin- and P-cadherin-positive and showed reduced membranous expression in all the catenins; Serous carcinomas were frequently N-cadherin- and P-cadherin-positive, mucinous tumors strongly expressed E-cadherin and the catenins in the membrane, and endometrioid tumors characteristically expressed nucleocytoplasmic beta-catenin in most of the cases. We next studied whether allelic losses in the chromosomal regions containing various cadherin genes (16q22) or APC gene (5q21) occurred in ovarian tumors and observed a high frequency of loss of heterozygosity in 16q22 (78%) and 5q21 (33%) regions, but there were no differences among the tumor types analyzed. Finally, we also assessed the molecular alterations responsible for beta-catenin nuclear accumulation in endometrioid tumors by screening for mutations in AXIN1, AXIN2, APC, and KRAS genes. Mutations in KRAS were observed in 2 of 19 tumors, but no mutations were detected in AXIN1, AXIN2, or APC genes. Only beta-catenin gene mutations were associated with nuclear beta-catenin staining in these tumors. In conclusion, different cadherin-catenin expression patterns are associated with distinct histologic types. Oncogenic Wnt signaling plays a role only in endometrioid tumors, where beta-catenin mutations seem to be the main cause of its aberrant expression.