Risk factors for lymphedema after breast surgery: A prospective cohort study in the era of sentinel lymph node biopsy.

INTRODUCTION: The Objective was to investigate the incidence of lymphedema after breast cancer treatment and to analyze the risk factors involved in a tertiary level hospital. METHODS: Prospective longitudinal observational study over 3 years post-breast surgery. 232 patients undergoing surgery for breast cancer at our institution between September 2013 and February 2018. Sentinel lymph node biopsy (SLNB) or axillary lymphadenectomy (ALND) were mandatory in this cohort. In total, 201 patients met the inclusion criteria and had a median follow-up of 31 months (range, 1-54 months). Lymphedema was diagnosed by circumferential measurements and truncated cone calculations. Patients and tumor characteristics, shoulder range of motion limitation and local and systemic therapies were analyzed as possible risk factors for lymphedema. RESULTS: Most cases of lymphedema appeared in the first 2 years. 13.9% of patients developed lymphedema: 31% after ALND and 4.6% after SLNB (p < 0.01), and 46.7% after mastectomy and 11.3% after breast-conserving surgery (p < 0.01). The lymphedema rate increased when axillary radiotherapy (RT) was added to radical surgery: 4.3% for SLNB alone, 6.7% for SLNB + RT, 17.6% for ALND alone, and 35.2% for ALND + RT (p < 0.01). In the multivariate analysis, the only risk factors associated with the development of lymphedema were ALND and mastectomy, which had hazard ratios (95% confidence intervals) of 7.28 (2.92-18.16) and 3.9 (1.60-9.49) respectively. CONCLUSIONS: The main risk factors for lymphedema were the more radical surgeries (ALND and mastectomy). The risk associated with these procedures appeared to be worsened by the addition of axillary radiotherapy. A follow-up protocol in patients with ALND lasting at least two years, in which special attention is paid to these risk factors, is necessary to guarantee a comprehensive control of lymphedema that provides early detection and treatment.

Long-term predictors of residual or recurrent cervical intraepithelial neoplasia 2-3 after treatment with a large loop excision of the transformation zone: a retrospective study.

OBJECTIVE: To assess the long-term risk factors predicting residual/recurrent cervical intraepithelial neoplasia (CIN 2-3) and time to recurrence after large loop excision of the transformation zone (LLETZ). DESIGN: Retrospective study. SETTING: Colposcopy clinic. POPULATION: 242 women with CIN 2-3 treated between 1996 and 2006 and followed up until June 2016. METHODS: Age, margins, and high-risk human papillomavirus (HR-HPV) were estimated using Cox proportional hazard and unconditional logistic regression models. The cumulative probability of treatment failure was estimated by Kaplan-Meier analysis. MAIN OUTCOME MEASURE: Histologically confirmed CIN 2-3, HR-HPV, margins, age. RESULTS: CIN 2-3 was associated with HR-HPV (HR = 30.5, 95% confidence interval [CI] = 3.80-246.20), age >35 years (HR = 5.53, 95% CI = 1.22-25.13), and margins (HR = 7.31, 95% CI = 1.60-33.44). HR-HPV showed a sensitivity of 88.8% and a specificity of 80%. Ecto+ /endocervical+ (16.7%), uncertain (19.4%) and ecto- /endocervical+ margins (9.1%) showed a higher risk of recurrence (odds ratio [OR] = 13.20, 95% CI = 1.02-170.96; OR = 15.84, 95% CI = 3.02-83.01; and OR = 6.60, 95% CI = 0.88-49.53, respectively). Women with involved margins and/or who were HR-HPV positive had more treatment failure than those who were HR-HPV negative or had clear margins (P-log-rank <0.001). CONCLUSIONS: HR-HPV and margins seem essential for stratifying post-LLETZ risk, and enable personalised management. Given that clear margins present a lower risk, a large excision may be indicated in older women to reduce the risk. TWEETABLE ABSTRACT: After LLETZ for CIN 2-3, recurrences appear more often in women with positive HR-HPV and involved margins and aged over 35.

Ganglios axilares contralaterales: enfermedad sistémica versus metástasis de un cáncer de mama oculto. Descripción de dos casos clínicos: el seguimiento es la clave para el diagnóstico / No disponible

Las metástasis axilares contralaterales en el cáncer de mama constituyen un hecho poco frecuente, y pueden corresponder tanto a la manifestación de una enfermedad sistémica (estadío IV) como a una metástasis de un cáncer primario oculto ipsilateral (TxN1, estadío II). La incertidumbre que rodea esta presentación clínica, sobre todo en relación a la lateralidad del cáncer que ha originado la metástasis, complica frecuentemente la clasificación y el manejo de estas pacientes. Tan sólo unas diferencias significativas en los niveles de receptores de estrógenos, progestágenos o sobreexpresión de HER- 2/neu podrían sugerir el diagnóstico. Se presentan dos pacientes con metástasis axilares contralaterales (MAC) en el contexto de un cáncer de mama, en las cuales, en el momento de la presentación, no había evidencia de enfermedad sistémica. Sin embargo el diagnóstico de presunción y tratamiento inicial fueron diferentes: el primer caso se consideró metastásico por lo que se trató con radioterapia radical y el segundo caso se consideró como carcinoma de mama bilateral por lo que se realizó linfadenectomía axilar. La evolución de las pacientes se desarrolló de forma contraria a la esperada, ya que el primer caso se comportó como un carcinoma de mama bilateral, mientras que el segundo desarrolló metástasis hepáticas(AU)

Metastases to the contralateral axillary lymph nodes in breast cancer patients are uncommon. Involvement of the contralateral axilla is a manifestation of systemic disease (stage IV) or a regional metastasis from a new occult primary (TxN1, stage II) The uncertain laterality of the cancer responsible for these metastases complicates overall disease staging and is a management dilemma for clinicians. Only a significant difference in estrogen and progesterone receptor levels or HER- 2/neu overexpression could ascertain the diagnosis. Two women who developed contralateral axillary metastases (CAM), but did not have evidence of systemic disease were identified. Presumption diagnosis and treatment of the CAM were different in both cases: metastatic breast cancer and radical radiotherapy in the first patient and bilateral breast cancer with axillary lymph node dissection in the second patient. After follow up of both cases, different final diagnosis were made: primary contralateral breast cancer in the first case, and liver metastases in the second one(AU)

Carcinoma de células fusiformes tipo “fibromatosis-like”: una variante inusual de carcinoma metaplásico de mama asociado a carcinoma ductal / No disponible

El carcinoma de células fusiformes tipo fibromatosis-like esuna variante del carcinoma metaplásico, que ha sido reconocidorecientemente como una entidad distinta e independiente del restode los tumores metaplásicos, que recuerda a la fibromatosis yse caracteriza por ser un tumor de bajo grado, con mejor pronósticoy tendencia a la recidiva local. Presentamos un caso de unapaciente de 71 años con un carcinoma tipo fibromatosis-likeasociado a un carcinoma ductal de la mama. La histología revelóun tumor de células fusiformes simulando una fibromatosis, dondese puede identificar un componente epitelial en forma de carcinomaductal o intraductal en continuidad con el componente deaspecto fusiforme. Inmunohistoquímicamente presentó positividadfocal para marcadores epiteliales y mioepiteliales como citoqueratinasy expresión de marcadores mesenquimales como vimentina.El diagnóstico exacto puede presentar dificultad tantoradiológica como anatomopatológica y plantea el diagnóstico diferencialcon lesiones benignas como fibromatosis, fascitis nodularo malignas como sarcomas. El comportamiento y pronósticono ha sido del todo aclarado aunque se ha visto que es un tumorque se caracteriza por un alto riesgo de recidiva, bajo potencialpara metastatizar en ganglios linfáticos regionales pero con capacidadpara producir metástasis a distancia y por tanto, debería sertratado en consecuencia(AU)

Fibromatosis-like spindle cell carcinoma of the breast is avariant of metaplastic carcinoma that has recently been recognizedas a different entity because of its resemblance to fibromatosisand similar propensity for local recurrence. We presenta case of 71- year-old lady with a fibromatosis-like carcinomaassociated with ductal carcinoma of the breast. Finalhistology revealed a tumor with predominant spindle cells in acollagenous background, simulating a fibromatosis. Inmunohistochemistryshowed focal positivity of ephithelial and myoephitelialmarkers as citokeratins and expression of mesenchymalmarker as vimentin in the tumor. This tumor can posediagnostic difficulty radiologic as histopathology and the differentialdiagnosis includes both benign and malignant spindlecell breast lesions as a fibromatosis, nodule fascitis or sarcomas.The behaviour and prognosis have not been well clarifiedalthough there seems to have high risk of local recurrence, lowpotential to metastasize to regional lymph nodes and potentialfor distant metastasis and should be treated accordingly(AU)

Miofibroblastoma mixoide mamario / No disponible

El miofibroblastoma es un tumor muy poco frecuente,perteneciente a la familia de tumores benignos de células fusiformesdel estroma mamario. El miofibroblastoma mixoiderepresenta una rara variante histológica compuesta predominantementepor estroma mixoide, que puede plantearnosdificultades diagnósticas con otros tipos de lesiones mixoides.Presentamos un caso de un tumor en una mujer joven enque las características clínicas y de imagen sugerían un tumorbenigno y finalmente la histología y la inmunohistoquímicaconfirmaron el diagnóstico de miofibroblastoma mixoide mamario(AU)

Myofibroblastoma is an unusual tumor that belongs to thefamily of benign spindle cell tumor of the mamary stroma. Myxoidmyofibroblastoma is a rare histological variant composedpredominantly of a myxoid stroma, this can pose diagnosticproblems with other types of myxoid lesions.We report a case in a young woman which suggested by clinicaland radiological a benign tumor. Finally the histology andimmunohistochemistry confirmed the diagnostic of myxoidmyofibroblastoma of the breast(AU)

Duration of ruptured membranes and extended labor are risk factors for HIV transmission.

OBJECTIVES: To determine the effects of duration of ruptured membranes (DRM) and duration of labor in HIV transmission. METHODS: A retrospective cohort study of 366 HIV-infected pregnant women and their infants analyzed the effects of these two variables; the cut-off point for transmission increase was estimated using a ROC curve. A multivariate analysis was performed with the most important risk factors according to the literature: maternal age, lymphocyte count, use of invasive procedures during gestation, antiretroviral treatment during pregnancy and labor, mode of delivery, newborn weight, DRM, labor duration, and the interaction of these last two factors. RESULTS: The cut-off points were estimated at 6 h for DRM and at 5 h for labor duration. A lymphocyte count below 500 cells/ml, use of invasive procedures, use of antiretroviral treatment during pregnancy and interaction between DRM, and labor duration remained significant in perinatal HIV transmission (P<0.05). CONCLUSIONS: An increased DRM increased perinatal HIV transmission when it was associated with prolonged labor.

Intrapartum fetal invasive procedures and perinatal transmission of HIV.

OBJECTIVE: To study the effect of intrapartum use of fetal invasive procedures (scalp electrodes or scalp pH sampling) on perinatal transmission rate of HIV. STUDY DESIGN: We compared the perinatal transmission of 57 HIV pregnancies in which invasive procedures (IP) were performed with a control group of 214 pregnancies without IP. We controlled for potentially risk factors (maternal CD4 level, gestational age, antiretroviral therapy use, duration of rupture of membranes (ROM), length of labor and mode of delivery) by stratification and logistic regression. RESULTS: Transmission rate in the group with IP was 26.3% (15/57) versus 13.6% (29/214) in the control group, relative risk (RR) 1.9, 95% CI (1.1-3.4). By logistic regression we observed three significant factors involved in transmission of HIV: low maternal CD4 level (odds ratio (OR)=3.3, 95% CI=1.2-9.4), duration of ROM (OR=2.9, 95% CI=1.1-7.9) and IP use (OR=3.5, CI 95%=1.2-9.6). Interaction between duration of ROM and IP are also significant (OR=5.1, CI 95%=1.5-17.5). CONCLUSIONS: Intrapartum use of fetal scalp electrodes or fetal scalp pH sampling increases the perinatal transmission of HIV and should therefore be avoided in HIV patients.

Study of an error-prone hypercycle formed from two kinetically distinguishable species.

Asymmetry within both the amplification factor values (Ak) and cross-catalytic hypercyclic constant (Kjk) and its influence on the stability of a two-membered error-prone hypercycle has been exhaustively studied from a deterministic point of view and the bifurcation diagram as a function of the quality factor (Q) has been obtained. In the more general case, several Q critical values appear, changing their relative position in the diagram depending on the Ak and Kjk values. The order of the Q critical values affects both the general properties of the system and the stability of the hypercyclic organization. The importance of this asymmetry in the selective and evolutionary properties of the hypercycle is also discussed.

A BASIC microcomputer program to calculate the secondary structure of proteins from their circular dichroism spectrum.

A BASIC program (CDPROT) has been developed to calculate the secondary structure of proteins from their far UV circular dichroism spectrum. This implementation can use different reference spectra, calculated either from model polypeptides or proteins of known tertiary structure. Apart from obtaining the alpha-helical, beta-structure, beta-turns or random percentages which would generate the spectrum of best fit with respect to the experimental measures, CDPROT represents on screen both theoretical and experimental spectra indicating the root-mean-square error. The provision of additional reference spectra by the user is also considered, and another program (STOREREF) performs the editing in an adequate format for CDPROT.

Influence of the hypercycle on the error threshold: a stochastic approach.

The role of fluctuations on the error threshold of the hypercycle has been studied by a stochastic approach on a very simplified model. For this model, the master equation was derived and its unique steady state calculated. This state implies the extinction of the system. But the actual time necessary to reach the steady state may be astronomically long whereas for times of experimental interest the system could be near some quasi-stationary states. In order to explore this possibility a Gillespie simulation of the stochastic process has been carried out. These quasi-stationary states correspond to the deterministic steady states of the system. The error threshold shifts towards higher values of the quality factor Q. Moreover, information about the fluctuations around the quasi-stationary states is obtained. The results are discussed in relation to the deterministic states.

Transition state of the glycolytic pathway under FDP saturating conditions: experimental studies and a theoretical model.

1. The transition state of the glycolytic pathway, under FDP saturating conditions, from no ADP to ADP-saturating levels, is studied in a metabolic model in vitro obtained from rat skeletal muscle. 2. When ADP is absent from the reaction mixture a steady state for NADH concentration is observed. After ADP addition, a new steady state is reached. The transition state from the first steady state to the second one shows a pulse of NADH. Both the profile and the size of this pulse depend on the enzyme concentration. 3. A kinetic model of the lower part of glycolysis (after PFK reaction) is proposed, and this is described by a set of first order coupled nonlinear differential equations. The results obtained through stability analysis and numerical integration of these equations agree with the experimental ones. 4. The possible role of the above mentioned transition state on the transmitter mechanism of glycolytic oscillations from PFK to the lower part of the glycolysis is discussed.

Studies on evolutionary and selective properties of hypercycles using a Monte Carlo method.

The most relevant properties of hypercycles were previously studied mainly from a theoretical point of view. We have developed a Monte Carlo method simulating hypercyclic organization to obtain information about the dynamics of this prebiotic organization. Nucleation, growth, and selective properties have been tested and the results obtained are in good agreement with those of the theoretical predictions. The influence of hypercyclic organization on the "error threshold" has also been studied. As a consequence of the emergence of a hypercycle, the value of this threshold decreases. The amount of this decrease depends on the population size. Moreover, for some interval of quality factor values, either the hypercycle organization or an error catastrophe can be produced, depending on the initial conditions. The influence of these phenomena on both the dynamic behavior and evolutionary advantages of the hypercycle, as well as their decisive roles on genome size, are discussed.