Clustering Molecular Subtypes in Breast Cancer, Immunohistochemical Parameters and Risk of Axillary Nodal Involvement.

(1) Background: To establish similarities in the risk of axillary lymph node metastasis between different groups of women with breast cancer according to immunohistochemical (IHC) parameters. (2) Methods: Data was collected retrospectively, from 2000 to 2013, of 1058 node-positive breast tumours. All patients were divided according to the St Gallen 2013 criteria and IHC features. The proportion of axillary involvement (pN > pN0; pN > pN1mi; pN > pN1) was calculated for each group. Similarities in axillary nodal dissemination were explored by cluster analysis and association between IHC and risk of axillary disease was studied with multivariate analysis. (3) Results: Among clinico-pathological surrogates of intrinsic subtypes, axillary involvement was more frequent in Luminal-B like HER2 negative (45.8%) and less frequent in Luminal-B HER2 positive (33.8%; p = 0.044). Axillary macroscopic involvement was more frequent in Luminal-B like HER2 negative (37.9%) and HER2 positive (37.8%) and less frequent in Luminal-B HER2 positive (25.5%) and Luminal-A like (25.6%; p = 0.002). Axillary involvement ≥pN2 was significantly less frequent in Luminal-A like (7.4%; p < 0.001). Luminal-A with Luminal-B HER2 positive, and triple-negative with Erb-B2 overexpressing tumours were clustered together regarding any axillary involvement, macroscopic disease or ≥pN2. Among the defined subgroups, axillary metastases were more frequent when Ki67 was higher. In a multivariate analysis, Ki67>14% were associated with a risk of axillary metastases (HR: 1.31; 95% CI, 1.51−6.80; p < 0.037). (4) Conclusions: there are two lymphatic drainage pathways of the breast according to the expression of hormone receptor-related genes. Positive-ER tumors are associated with lower axillary involvement and negative-ER tumors and Ki67 > 14% with higher nodal involvement.

Activity of docetaxel, carboplatin, and doxorubicin in patient-derived triple-negative breast cancer xenografts.

Triple-negative breast cancer (TNBC) is highly responsive to neoadjuvant polychemotherapy regimens including anthracyclines, taxanes, and, more recently, carboplatin. However, there is inadequate information on the individual contribution of each of these agents to the global activity of the combinations, and the use of combinations of up to four of these drugs is associated with relevant toxicity. Identifying single-drug activity in the clinical neoadjuvant setting is challenging. We developed patient-derived xenografts (PDXs) from several chemotherapy-naïve TNBC samples to assess the antitumor activity of single drugs and combinations of drugs. PDXs were established from chemotherapy-naïve TNBC samples. Nine TNBC PDX models (all of which corresponded to a basal-like phenotype according to the PAM50 classifier) were treated with carboplatin, docetaxel, and doxorubicin and the combination of docetaxel and carboplatin. Only one of nine PDX models showed sensitivity to doxorubicin, while eight of nine PDX models showed sensitivity to docetaxel and carboplatin as single agents. The 3 PDX models derived from patients with gBRCA-1 or gPALB2 mutations were very sensitive to carboplatin single agent. All 6 PDX models from patients without hereditary germ-line mutations showed increased sensitivity to the combination of docetaxel and carboplatin. In the present study, docetaxel and carboplatin single agents were active drugs against basal-like TNBC, while doxorubicin monotherapy showed low activity. The combination of docetaxel and carboplatin was more effective than the drugs used as single agents, except in the PDX from patients with gBRCA1/PALB2 mutations.

SARS-CoV-2 screening of asymptomatic women admitted for delivery must be performed with a combination of microbiological techniques: an observational study / El cribado de SARS-CoV-2 en mujeres asintomáticas admitidas en trabajo de parto se debe realizar con una combinación de técnicas microbiológicas: un estudio observacional

INTRODUCTION: The aim of this study is to assess the value of systematic screening in asymptomatic women admitted for spontaneous delivery with a combination of reverse transcription polymerase chain reaction (RT-PCR) and cycle threshold (Ct) and serum antibodies. MATERIAL AND METHODS: Since May 6 all women admitted for spontaneous delivery underwent RT-PCR in nasopharyngeal swabs and specific antibodies IgG of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in serum that were performed as part of routine clinical care in our institution. Ct of the PCR was recorded. We analyzed the first 100 women consecutively admitted for spontaneous delivery at our institution. RESULTS: Nine women were positive for SARS-CoV-2 in nasopharyngeal samples (9%) and 13 (13%) presented positive specific antibodies of the coronavirus. Overall, SARS-CoV-2 prior exposure was 15%. The Ct determination (RT-PCR test) of our 9 positive patients ranged from 36 to 41 cycles with a median of 40. Vaginal delivery occurred in 94% of the cases and only 6% underwent a cesarean section, always for obstetric reasons. No fetal transmission was observed and maternal and neonatal prognosis was excellent. CONCLUSIONS: During epidemic episodes in asymptomatic women in labor, universal testing with RT-PCR (considering Ct determination), and the detection of antibodies, permits a better interpretation of the results and avoid unnecessary isolation procedures

OBJETIVO: El objetivo de este estudio es evaluar, en mujeres asintomáticas que acuden a urgencias en trabajo de parto, el valor de la detección sistemática con una combinación de reacción en cadena de la polimerasa con transcriptasa inversa (RT-PCR) y umbral del ciclo (Ct) y anticuerpos séricos. MATERIAL Y MÉTODOS: Desde el 6 de mayo, todas las mujeres ingresadas para parto espontáneo se sometieron a RT-PCR en hisopos nasofaríngeos y anticuerpos específicos IgG del síndrome respiratorio agudo severo por coronavirus 2 (SARS-CoV-2) en suero que se realizaron como parte de la atención clínica de rutina en nuestra institución. Se registró el Ct de la PCR. Analizamos las primeras 100 mujeres admitidas consecutivamente para parto espontáneo en nuestra institución. RESULTADOS: Nueve mujeres fueron positivas para SARS-CoV-2 en muestras nasofaríngeas (9%) y 13 (13%) presentaron anticuerpos específicos positivos del coronavirus. En general, la exposición previa a SARS-CoV-2 fue del 15%. La determinación de Ct (prueba de RT-PCR) de nuestros 9 pacientes positivos varió de 36 a 41 ciclos con una mediana de 40. El parto vaginal se produjo en el 94% de los casos y solo el 6% se sometió a una cesárea, siempre por razones obstétricas. No se observó transmisión fetal y el pronóstico materno y neonatal fue excelente. CONCLUSIONES: Durante los episodios epidémicos en mujeres asintomáticas en trabajo de parto, las pruebas universales con RT-PCR (considerando la determinación de Ct) y la detección de anticuerpos, permiten una mejor interpretación de los resultados y evitan procedimientos de aislamiento innecesarios

Correlation between Anatomical Segments of the Pudendal Nerve and Clinical Findings of the Patient with Pudendal Neuralgia.

BACKGROUND: The objective was to describe clinical findings and outcomes of patients with pudendal neuralgia in relation with the anatomical segment affected. METHODS: Fifty-one consecutive patients with chronic perineal pain (CPP) located in the areas supplied by the pudendal nerve (PN), from January 2011 to June 2012, were analyzed. RESULTS: The distribution of pain at perineal, dorsal clitoris and inferior anal nerves was 92.2, 31.4 and 25.5% respectively. The duration of pain was longer when the dorsal clitoris nerve (DCN) was affected (p < 0,003). The pain in the pudendal canal was frequently associated with the radiation of pain to the inferior members (p < 0.043). CONCLUSION: CPP and radiation of pain to lower limbs suggest a disorder at the second segment of PN. A positive Tinel sign in the third segment indicates a nerve entrapment. In terminal branches, pain was more frequent at the perineal nerve and more persistent at the DCN.

Evaluation of Breast Cancer Patients with Genetic Risk in a University Hospital: Before and After the Implementation of a Heredofamilial Cancer Unit.

The identification of patients at risk for breast cancer by genetic testing has proven to reduce breast cancer mortality. In 2010, due to a lack of systematization in hereditary cancer assistance in our center, we implemented a multidisciplinary Heredofamilial Cancer Unit (HFCU). We analyze if the HFCU improved the rates of referrals and preventive management of breast cancer patients with genetic risk. We retrospectively compared family history records, referrals of high-risk patients to genetic counseling, and detection and management of patients with BRCA1/2 mutations in two cohorts of breast cancer patients diagnosed before (first period: 2007-2010) and after the creation of the HFCU (second period: 2010-2013). In the first period, 893 patients were included, and 902 were included in the second. Due to the inability to establish their genetic risk, 142 patients (15.9%) vs. 70 (7.8%) were excluded from analysis (p < 0.001). Among the evaluable patients, 194 (25.8%) vs. 223 (26.8%) fulfilled one or more risk criteria (p = 0.65). Family history documentation in patient's medical records (92.4 vs. 97.8%, p < 0.001) and referral rate (26.3 vs. 52%, p < 0.0001) significantly increased in the second period. Eight BRCA1/2 mutations were detected among patients referred in the first period and 17 among those referred to the HFCU. The rate of preventive surgeries in patients with BRCA mutations significantly increased in the second period (25 vs. 76.5%, p = 0.03). In conclusion, there was a clear improvement in family history records, referrals, and preventive surgeries in breast cancer patients with genetic risk after the implementation of the HFCU.

Maternal and perinatal outcomes in pregnancy-associated melanoma. Report of two cases and a systematic literature review.

OBJETIVES: Melanoma is one of the most frequent malignancies during gestation. However, oncological and perinatal management is still challenging. Our first objective is to describe the cases of pregnancy-associated melanoma (PAM) diagnosed in our centre between January-2004 and May-2015. Secondly, to perform a systematic review of the published articles analysing the maternal-perinatal outcomes of patients diagnosed with PAM. DESIGN, POPULATION AND METHODS: Obstetrical, oncological and perinatal variables were recorded in the case series. For the systematic review we include all published articles assessing the obstetric and neonatal outcomes in PAM cases in Pubmed, Web of Knowledge and Cochrane Library. The search was restricted to articles published in English, between January-2004 and May-2015. Study characteristics, oncological and maternal-perinatal variables were recorded in the systematic review. RESULTS: Two patients were found: the first case presents a newly diagnosed metastatic melanoma at 26-weeks of gestation with fatal maternal and neonatal outcome. The second case presents a patient with metastatic melanoma who got pregnant during her treatment. For the systematic review we found 25 articles, providing data from 489 patients. Maternal-perinatal outcomes, including termination of pregnancy rates, vary depending on the country, gestational age and tumour stage at diagnosis. PAM is usually detected at advanced stages, even with metastasis affecting the placenta and the foetus. CONCLUSIONS: When diagnosed at early stages, melanoma does not seem to alter the evolution of gestation, whereas patients with advanced stages of melanoma frequently deliver prematurely, by caesarean section, with lower neonatal weight, higher neonatal morbidity and mortality rates.

"The impact of debulking surgery in patients with node-positive epithelial ovarian cancer: Analysis of prognostic factors related to overall survival and progression-free survival after an extended long-term follow-up period".

OBJECTIVE: to estimate the prognostic factors associated with survival and progression free survival (PFS) in patients with node-positive epithelial ovarian cancer (EOC) after an extended long-term follow-up period. METHODS: Data was provided by the Tumor Registry of the Mayo Clinic, Scottsdale, Arizona on 116 node-positive EOC patients who underwent primary cytoreductive surgery observed over the period 1996-2014. RESULTS: At censoring date, 21 patients were alive (18%), 95 dead (82%), 18 without evidence of disease (NED) (15 alive, 3 dead) and 76 with evidence of disease (ED) (2 alive, 74 dead). Twenty-nine ED patients (38.2%) experienced a recurrence within 2 years, 53 patients (69.7%) before 5 years. No recurrences were recorded after 10 years. The median follow-up in alive patients was 169.8 months (1.20-207.9 months), 34.9 months (0.30-196.2 months) in dead patients, 128.4 months for NED patients (72.8-202.5 months) and 34.6 months (0.1-106.9 months) in ED patients. Multivariate analysis showed an increased risk of dead in patients with age ≥ 60 years (HR: 3.20; p < 0.002), stage IVA/B (compared with stage IIIA1/2, HR: 4.31; p < 0.001 and stage IIIB/C, HR: 5.31; p < 0.010) and incomplete surgery (compared with complete surgery, HR: 3.10; 95% CI, 1.41-6.77; p < 0.003) and a decreased PFS in stage IVA/B (compared with stages IIIB/C; p = 0.003 and stage IIIA; p = 0.000) and residual volume after surgery >0.6 cm (compared with residual disease <0.5 cm; p < 0.023). CONCLUSIONS: prognostic factors for an extended long-term PFS are similar as those for survival, because after 17-year follow-up period, the majority of alive patients are NED patients.

Peritoneal carcinomatosis: A malignant disease with an embryological origin?

INTRODUCTION: In 1931, Simpson et al. coined the term "peritoneal carcinomatosis" to describe the regional spread of ovarian tumors as localized or extended with involvement of the peritoneal serous membrane and neighboring anatomical structures. Research into the origin of peritoneal carcinomatosis is based on two phases in a woman's life: EMBRYO DEVELOPMENT: During week 3, the bilaminar disc becomes a trilaminar disc called the mesoderm. Inside the lateral plate mesoderm, the coelomic cavity is divided into 2 layers: the parietal (somatic) mesoderm, which gives rise to the parietal peritoneum and pleural surfaces; and the visceral (splanchnic) mesoderm, which gives rise to the visceral peritoneum, visceral surface of the pleura, gonadal stroma, and the muscular layer of the hollow viscera and its mesenteries. TUMOR SPREAD: Transcoelomic metastasis and metaplasia of pluripotent stem cells in the peritoneum was involved in the pathogenesis of ovarian cancer. This involvement takes the form of a synchronous malignant transformation at multiple foci and may cause intraperitoneal field cancerization. Pluripotent stem cells play a role both in the development of the embryonic peritoneum and in the spread of transcoelomic tumors. Consequently, knowledge of the origin of these cells (embryonic or current) could be extremely useful. The many markers that act during the embryonic period can affect descendants, that is, cells are already marked before specification and differentiation are activated. Thus, programmed activation could be attributed to genetic and epigenetic changes.

Single-Institution Multidisciplinary Management of Locoregional Oligo-Recurrent Pelvic Malignancies: Long-Term Outcome Analysis.

PURPOSE: The aim of this study was to analyze long-term outcomes and prognostic factors associated with survival in patients with locoregional oligo-recurrent (LROR) pelvic malignancies treated in a multimodal protocol. METHODS: Patients with an histologic diagnosis of LROR pelvic cancer (rectal 50 %, gynecological 50 %) with absence of distant metastases, undergoing surgery with radical intent and intraoperative radiotherapy (median dose 12.5 Gy) were considered eligible for participation in this study. Additionally, 48 % received external beam radiotherapy (EBRT) (median dose 50 Gy). RESULTS: From 1995 to 2012, a total of 143 patients from a single institution were analyzed. With a median follow-up time of 48 months (range 2-189), 5-year locoregional control (LRC), disease-free survival (DFS), and overall survival (OS) were 53, 44, and 46 %, respectively. On multivariate analysis, no EBRT treatment to the locoregional (p ≤ 0.001), R1 margin status (p = 0.03), time interval from primary tumor diagnosis to LROR <24 months (p = 0.05), and fragmentation in the resected specimen (p = 0.004) retained significance in relation to LRC. On multivariate analysis we found that only R1 margin status (p = 0.003), primary tumor diagnosis to LROR <24 months (p = 0.02), and high histological grade (p = 0.02) were significantly associated with OS. CONCLUSIONS: From this analysis emerges the fact that EBRT influences local control but, given the high risk of distant metastases, DFS remains modest. Margin status, tumor fragmentation, no EBRT to the LR, and time interval from primary tumor diagnosis to LROR are the dominant factors for subsequent locoregional recurrence (LRR). Accordingly, future prospective studies might be designed which adapt treatment according to the predicted risk of subsequent LRR.