Cryoablation Without Excision for Low-Risk Early-Stage Breast Cancer: 3-Year Interim Analysis of Ipsilateral Breast Tumor Recurrence in the ICE3 Trial.

BACKGROUND: The ICE3 trial is designed to evaluate the safety and efficacy of breast cryoablation, enabling women older than 60 years with low-risk early-stage breast cancers to benefit from a nonsurgical treatment and to avoid the associated surgical risks. METHODS: The ICE3 trial is a prospective, multi-center, single-arm, non-randomized trial including women age 60 years or older with unifocal, ultrasound-visible invasive ductal carcinoma size 1.5 cm or smaller and classified as low to intermediate grade, hormone receptor (HR)-positive, and human epidermal growth factor receptor 2 (HER2)-negative. Ipsilateral breast tumor recurrence (IBTR) at 5 years was the primary outcome. A 3-year interim analysis of IBTR was performed, and the IBTR probability was estimated using the Kaplan-Meier method. RESULTS: Full eligibility for the study was met by 194 patients, who received successful cryoablation per protocol. The mean age was 75 years (range, 55-94 years). The mean tumor length was 8.1 mm (range, 8-14.9 mm), and the mean tumor width was 7.4 mm (range, 2.8-14 mm). During a mean follow-up period of 34.83 months, the IBTR rate was 2.06% (4/194 patients). Device-related adverse events were reported as mild in 18.4% and moderate in 2.4% of the patients. No severe device-related adverse events were reported. More than 95% of the patients and 98% of the physicians reported satisfaction with the cosmetic results at the clinical follow-up evaluation. CONCLUSIONS: Breast cryoablation presents a promising alternative to surgery while offering the benefits of a minimally invasive procedure with minimal risks. Further study within a clinical trial or registry is needed to confirm cryoablation as a viable alternative to surgical excision for appropriately selected low-risk patients.

Tmem2 restricts atrioventricular canal differentiation by regulating degradation of hyaluronic acid.

BACKGROUND: Atrioventricular valve development relies upon the precisely defined dimensions of the atrioventricular canal (AVC). Current models suggest that Wnt signaling plays an important role atop a pathway that promotes AVC development. The factors that confine AVC differentiation to the appropriate location, however, are less well understood. RESULTS: Transmembrane protein 2 (Tmem2) is a key player in restricting AVC differentiation: in zebrafish, tmem2 mutants display an expansion of AVC characteristics, but the molecular mechanism of Tmem2 function in this context remains unclear. Through structure-function analysis, we demonstrate that the extracellular portion of Tmem2 is crucial for its role in restricting AVC boundaries. Importantly, the Tmem2 ectodomain contains regions implicated in the depolymerization of hyaluronic acid (HA). We find that tmem2 mutant hearts exhibit excess HA deposition alongside broadened distribution of Wnt signaling. Moreover, addition of ectopic hyaluronidase can restore the restriction of AVC differentiation in tmem2 mutants. Finally, we show that alteration of a residue important for HA depolymerization impairs the efficacy of Tmem2 function during AVC development. CONCLUSIONS: Taken together, our data support a model in which HA degradation, regulated by Tmem2, limits the distribution of Wnt signaling and thereby confines the differentiation of the AVC.

Tmem2 regulates cell-matrix interactions that are essential for muscle fiber attachment.

Skeletal muscle morphogenesis depends upon interactions between developing muscle fibers and the extracellular matrix (ECM) that anchors fibers to the myotendinous junction (MTJ). The pathways that organize the ECM and regulate its engagement by cell-matrix adhesion complexes (CMACs) are therefore essential for muscle integrity. Here, we demonstrate the impact of transmembrane protein 2 (tmem2) on cell-matrix interactions during muscle morphogenesis in zebrafish. Maternal-zygotic tmem2 mutants (MZtmem2) exhibit muscle fiber detachment, in association with impaired laminin organization and ineffective fibronectin degradation at the MTJ. Similarly, disorganized laminin and fibronectin surround MZtmem2 cardiomyocytes, which could account for their hindered movement during cardiac morphogenesis. In addition to ECM defects, MZtmem2 mutants display hypoglycosylation of α-dystroglycan within the CMAC, which could contribute to the observed fiber detachment. Expression of the Tmem2 ectodomain can rescue aspects of the MZtmem2 phenotype, consistent with a possible extracellular function of Tmem2. Together, our results suggest that Tmem2 regulates cell-matrix interactions by affecting both ECM organization and CMAC activity. These findings evoke possible connections between the functions of Tmem2 and the etiologies of congenital muscular dystrophies, particularly dystroglycanopathies.

[Anomalous origin of the right pulmonary artery from the ascending aorta associated with aortopulmonary window]. / Origen anómalo de la rama derecha de la arteria pulmonar de la aorta ascendente asociado con ventana aortopulmonar.

Anomalous origin of one pulmonary artery from the aorta is rare. We report a case of a three-month-old infant with aortopulmonary window and anomalous origin of the right pulmonary artery from the ascending aorta. He underwent surgery with anastomosis of the right pulmonary artery, ligation of the aortopulmonary window and the patent duct. He was released under medical treatment and had no signs of pulmonary hypertension or heart failure.

Giant Phyllodes Tumor in an 82-Year-Old Female Initially Diagnosed a Fibroadenoma: A Case Report.

Phyllodes tumors are a rare fibroepithelial neoplasm of the breast occurring in approximately 2.1 in every 1 million women with no clear predilection for women of specific races. They are characterized by spindle-shaped stromal cells with increased stromal cellularity and increased mitotic activity. The histologic characteristics are similar to that of cellular fibroadenomas making them frequently difficult to differentiate on core biopsy. We present a case of an 82-year-old female with a right breast mass which was initially diagnosed as a fibroadenoma in 2009. She was lost to follow-up and presented in 2021 with complaint of a right breast mass for which diagnostic imaging was performed. A diagnostic mammogram demonstrated a macrolobulated mass measuring 14×12×12 cm which corresponded to the palpable abnormality. The patient subsequently underwent simple mastectomy demonstrating a 14 cm mass with a fibroepithelial structure consistent with a borderline phyllodes tumor. The patient received adjuvant radiotherapy to minimize the likelihood of local recurrence. We concluded that reliable preoperative diagnosis and further studies regarding guidelines for adequate tumor margins and indication for adjuvant radiotherapy are crucial for proper surgical planning and follow-up after excision.

[Transcatheter occlusion of the patent ductus arteriosus with detachable coils: immediate results and intermediate-term follow-up]. / Cierre transcatéter del conducto arterioso permeable con coils de liberación controlada: resultados inmediatos y seguimiento a mediano plazo.

OBJECTIVE: To determine the success rate and safety of percutaneous closure of patent ductus arteriosus (PDA) with a detachable coil. METHODS: Forty-one children with small- to moderate-size PDA (maximum diameter < or = 4 mm) underwent percutaneous coil occlusion. The results were assessed by angiography and echocardiography. The mean age was 2.0 +/- 1.3 years (range 0.6 to 5.6 years); mean weight was 10.0 +/- 3.4 kg (range 4.5 to 18.0 kg). The mean minimum diameter of the PDA was 1.7 +/- 0.6 mm (range, 0.5 to 4.0 mm). RESULTS: The occlusion device was inserted in 39 of 41 patients (95%). The mean coil/PDA ratio was 3.41 +/- 1.1. We observed angiographic cessation of blood flow through the PDA after coil insertion in 18 patients; 18 patients had residual shunt, 3 mild shunt and 2 moderate shunt. No complications were observed during the procedure. Thirty-five patients showed absence of blood flow through PDA 24 hours after coil occlusion by echocardiography. The other four patients with residual shunt showed flow cessation after 2 months in two patients and after 6 months in the other two. Failure of coil insertion in two patients was due to detachment of the pulmonary edge of the coil, which was subsequently removed in one, and due to coil migration in the other, both patients underwent surgical PDA closure. Mean follow-up at 29.5 +/- 16.5 months showed no residual blood flow through the occluded PDA, except for one patient. CONCLUSION: Our results, as many others, suggest that PDA coil occlusion is a safe, effective, and cheap procedure. PDA coil occlusion should be the elective method for PDA closure in patients older than 6 months of age with small- to moderate size PDA (< or = 4 mm). The procedure in newborn infants and patients with larger PDA must be made with a different type of occlusive device.

[Prognostic factors associated with postoperative morbidity in children with isolated ventricular septal defect]. / Factores pronóstico de morbilidad posquirúrgica en pacientes pediátricos con comunicación interventricular aislada.

BACKGROUND: Isolated ventricular septal defect (VSD) is one of the most common congenital heart diseases worldwide. Prognostic factors associated with postoperative morbidity in patients with isolated VSD in the Hospital de Pediatría del Centro Médico Nacional Siglo XXI have not been identified. METHODS: A retrospective cohort study was conducted from January 1, 2009 to December 31, 2013. Descriptive statistics and comparisons between groups were performed using chi-square test, Mann Whitney U test and linear regression. Relative risks (RR) and 95 % confidence intervals (95% CI) were calculated. RESULTS: A total of 64 patients who underwent isolated VSD closure were included, 12.5 % (n = 8) had a history of pulmonary banding and 22 patients (34.3 %) had Down syndrome. The perimembranous and subaortic lesions occurred in 70 % of cases. Factors associated with an increased morbidity and a prolonged intensive care unit (ICU) stay were: lactate at the end of extracorporeal circulation (ECC) greater than 3 mmol/L (p = 0.02) and Down syndrome (p = 0.02), who had the highest incidence of postoperative complications (p = 0.02). CONCLUSIONS: A statistically significant association was found: the higher the preoperative functional class, the longer the hospital stay, the number of days at ICU and the hours of mechanical ventilation.

Introducción: la comunicación interventricular aislada (CIV) es una de las cardiopatías congénitas más frecuentes a nivel mundial. Se desconoce cuáles son los factores pronósticos asociados a la morbilidad postoperatoria de los pacientes con CIV aislada en el Hospital de Pediatría del Centro Médico Nacional Siglo XXI. Métodos: se realizó un estudio de cohorte retrospectivo del 1 de enero de 2009 al 31 de diciembre de 2013. Se utilizó estadística descriptiva y comparaciones entre los grupos mediante chi cuadrada, U de Mann Whitney y regresión lineal. Se calcularon riesgos relativos (RR) e intervalos de confianza al 95 % (IC 95%). Resultados: se incluyeron 64 pacientes a quienes se les realizó cierre de comunicación interventricular aislada. El 12.5 % (n = 8) tenían antecedente de cerclaje pulmonar y 22 (34.3 %) pacientes tenían síndrome de Down. Las CIV perimembranosas y la subaórtica se presentaron en 70 % de los casos. Los factores asociados a una mayor morbilidad y estancia prolongada en terapia intensiva fueron: lactato al final de la circulación extracorpórea (CEC) mayor a 3mmol/L (p = 0.02) y el síndrome de Down (p = 0.02) quienes presentaron una mayor frecuencia de complicaciones postoperatorias (p = 0.02). Conclusiones: se encontró una asociación estadísticamente significativa: cuanto mayor era la clase funcional preoperatoria, mayor era su estancia intrahospitalaria, con mayor número de días en terapia intensiva y mayor tiempo de ventilación mecánica asistida.

[Mortality-associated factors in pediatric patients with Blalock-Taussig shunt]. / Factores relacionados con mortalidad en pacientes pediátricos con derivación de Blalock-Taussig.

BACKGROUND: Congenital heart disease with decreased pulmonary flow survival has increased due to systemic pulmonary fistulae (SPF); nevertheless, complications may occur. The purpose of this study was to identify mortality-related surgical and biochemical factors in pediatric patients with modified Blalock-Taussig shunt. METHODS: A cohort was formed with congenital heart disease newborns who survived Blalock-Taussig-type palliative systemic pulmonary fistulae surgery. At admission to the intensive care unit, surgical time, diameter polytetrafluoroethylene vascular graft, arterial blood gases and central venous saturation were recorded. The patients were followed until discharge or death. For statistical analysis, central tendency and dispersion measures, chi-square tests, odds-ratios, Cox regression model and hazard ratios (HR) were used, and for the most independent variable, Kaplan-Meier curves. RESULTS: Out of 33 newborns who underwent the surgical procedure, 9 died (23%). The most common heart diseases were pulmonary atresia with intact ventricular septum (8 patients, 25%) and hypoplastic right ventricle (8, 25%). The most independent mortality-associated variable was hyperlactatemia > 3 mmol/L (HR = 8 [1.9 - 32], p < 0.05). CONCLUSIONS: Lactate > 3 mmol/L was an independent predictor of mortality in patients who underwent Blalock-Taussig shunt.

INTRODUCCIÓN: la supervivencia de los pacientes con cardiopatía congénita con flujo pulmonar disminuido ha aumentado debido a las técnicas de anastomosis quirúrgica entre la circulación sistémica y la pulmonar, sin embargo, pueden presentarse complicaciones. El objetivo de este estudio fue determinar los factores quirúrgicos y bioquímicos relacionados con la muerte en pacientes pediátricos en quienes se realizó derivación de Blalock-Taussig modificada. MÉTODOS: se integró una cohorte de neonatos con cardiopatía congénita sometidos a derivación tipo Blalock-Taussig que sobrevivieron a la cirugía. Al ingreso a cuidados intensivos se documentó tiempo quirúrgico, diámetro del injerto vascular de politetrafluoroetileno, gasometría arterial y saturación venosa central de oxígeno. Se dio seguimiento hasta el egreso o defunción. Para el análisis estadístico se utilizaron medidas de tendencia central y dispersión, chi cuadrada, razón de momios, modelo de regresión de Cox, hazard ratio (HR) y curva de Kaplan-Meier, para la variable más independiente. RESULTADOS: de 33 neonatos sometidos a procedimiento quirúrgico, nueve murieron (23 %). Las cardiopatías más frecuentes fueron la atresia pulmonar con septo íntegro (ocho, 25 %) y ventrículo derecho hipoplásico (ocho, 25 %). La variable más independiente relacionada con mortalidad lo constituyó el nivel del lactato sérico > 3 mmol/L (HR = 8 [1.9-32], p < 0.05). CONCLUSIONES: el nivel del lactato sérico > 3 mmol/L fue un predictor independiente de mortalidad en los pacientes con derivación tipo Blalock-Taussig.

Endoscopy for the initial suspicion of vascular rings in tracheoesophageal compressions: correlation with surgical findings.

UNLABELLED: Vascular rings (VR) may produce extrinsic compression of trachea and/or esophagus. Diagnosis relies on nonspecific clinical data from resulting compression and image studies, mainly angiography, computed tomography, and cardiovascular MRI. Because of their low incidence, diagnosis is often missed. The role of bronchoscopy and esophagoscopy is controversial, but these procedures might establish for the first time the diagnostic suspicion of VR. This communication was aimed to determine to what extent endoscopic manifestations lead the clinician to suspect the presence of a VR and, moreover, to define their correlation with surgical findings. METHODS: Children with endoscopic diagnosis of VR submitted to surgery were retrospectively analyzed. RESULTS: Twenty patients fulfilled inclusion criteria. They were submitted to 19 bronchoscopies and 16 esophagoscopies, and in 60% cases they raised the first suspicion of VR. Diagnostic agreement of the type of VR between endoscopy and surgery was 85%. Bronchoscopy diagnosed 12 VR, and in 10 cases predicted the specific type of VR. Additional relevant findings were detected in nine patients (47.4%). Esophagoscopy diagnosed VR in 14 patients, predicted the specific type in 78.6% and detected all aberrant right subclavian artery cases. CONCLUSIONS: Initial suspicion of VR was raised by bronchoscopic and/or esophagoscopic findings in 60% cases. Endoscopy proved to be a valuable tool to anticipate the type of malformation and to disclose associated abnormalities.

Cierre transcatéter del conducto arterioso permeable con coils de liberación controlada: Resultados inmediatos y seguimiento a mediano plazo / Transcatheter occlusion of the patent ductus arteriosus with detachable coils: immediate results and intermediate-term follow-up

Objetivo: Determinar la frecuencia de éxito y seguridad del cierre percutáneo del conducto arterioso permeable (CAP) con coils de liberación controlada. Método: Cuarenta y un pacientes pediátricos con conducto arterioso permeable (CAP), de un tamaño pequeño a moderado (diámetro mínimo < 4 mm), fueron sometidos a cierre percutáneo con coils de liberación controlada. Los resultados se establecieron mediante estudios angiográficos y ecocardiográficos. La media de edad fue de 2.0 ±1.3 años (rango, 0.6-5.6 años); la media de peso fue de 10.0 ± 3.4 kg (rango, 4.5-18.0 kg). La media del diámetro mínimo del CAP fue de 1.69 ± 0.6 mm (rango, 0.5-4 mm). Resultados: En 39/41 pacientes se logró la implantación del dispositivo (95%). La relación media del coil/CAP fue de 3.41 ±1.1. Inmediatamente posterior a la oclusión con el coil, 18 conductos arteriosos no mostraron flujo residual por angiografía; 18 tenían un cortocircuito residual trivial, 3 leve y 2 leve. No se presentaron complicaciones significativas con el procedimiento. En las primeras 24 horas posteriores a la implantación del coil, el control ecocardiográfico mostró oclusión completa en 35 pacientes. En los 4 pacientes con flujo residual, el seguimiento ecocardiográfico demostró ausencia del cortocircuito 3 meses después en 2 pacientes y 6 meses después en un paciente. En uno, no se ha logrado la oclusión completa a un año. En dos pacientes (5%) se abandonó el procedimiento: en un paciente, por mostrar flujo residual moderado y movimiento del extremo pulmonar del coil, que debió de ser retirado con un catéter lazo y en otro, por migración del coil. Ambos pacientes fueron enviados a cirugía. En un seguimiento medio de 29.5 ± 16.5 meses (rango, 0 a 60 meses) de los 39 pacientes, no se observó flujo residual por ecocardiografía Doppler color, excepto en uno. Conclusión: Nuestros resultados, en concordancia con otros autores, sugieren que la oclusión del conducto arterioso permeable con coils de liberación controlada, es un método seguro, efectivo y de bajo costo. La oclusión con coil deberá ser el procedimiento de elección en pacientes mayores de 6 meses de edad con conductos arteriosos permeables de un tamaño pequeño a moderado (< 4 mm). En la extensión de este procedimiento a recién nacidos y a pacientes con conductos arteriosos más grandes, deberá considerarse otro tipo de dispositivo oclusor.

Objective: To determine the success rate and safety of percutaneous closure of patent ductus arteriosus (PDA) with a detachable coil. Methods: Forty-one children with small-to moderate-size PDA (maximum diameter < 4 mm) underwent percutaneous coil occlusion. The results were assessed by angiography and echocardiography The mean age was 2.0 ± 1.3 years (range 0.6 to 5.6 years); mean weight was 10.0 ± 3.4 kg (range 4.5 to 18.0 kg). The mean minimum diameter of the PDA was 1.7 ± 0.6 mm (range, 0.5 to 4.0 mm). Results: The occlusion device was inserted in 39 of 41 patients (95%). The mean coil/PDA ratio was 3.41 ±1.1. We observed angiographic cessation of blood flow through the PDA after coil insertion in 18 patients; 18 patients had residual shunt, 3 mild shunt and 2 moderate shunt. No complications were observed during the procedure. Thirty-five patients showed absence of blood flow through PDA 24 hours after coil occlusion by echocar-diography The other four patients with residual shunt showed flow cessation after 2 months in two patients and after 6 months in the other two. Failure of coil insertion in two patients was due to detachment of the pulmonary edge of the coil, which was subsequently removed in one, and due to coil migration in the other, both patients underwent surgical PDA closure. Mean follow-up at 29.5 ± 16.5 months showed no residual blood flow through the occluded PDA, except for one patient. Conclusion: Our results, as many others, suggest that PDA coil occlusion is a safe, effective, and cheap procedure. PDA coil occlusion should be the elective method for PDA closure in patients older than 6 months of age with small-to moderate size PDA(< 4 mm). The procedure in newborn infants and patients with larger PDA must be made with a different type of occlusive device.

Cardiomiopatia mitocôndrica hipertrófica associada à síndrome de Wolff-Parkinson-White / Mitochondrial hypertrophic cardiomyopathy associated with Wolff-Parkinson-White syndrome

Atualmente, diversas doenças cardíacas são reconhecidas como de origem genética. As mutações em genes, que codificam várias proteínas do sarcômero com desarranjo miofibrilar e dos miócitos, e a mutação associada à síndrome de Wolff-Parkinson-White, identificada no cromossomo 7q3 como resultado de uma mutação pontual no gene, que codifica uma subunidade reguladora de AMP - proteína quinase ativada, expressa em hipertrofia ventricular, pré-excitação ventricular ou ambas, são dois exemplos de cardiomiopatia hipertrófica familiar 1-3. Outras doenças cardíacas congênitas, nas quais a cardiomiopatia hipertrófica ou dilatada e distúrbios elétricos, podem estar presentes em cerca de 20 a 30 por cento de pacientes, incluem algumas doenças mitocondriais4-6. Apresentamos um caso de uma recém nascida com taquicardia persistente secundaria à síndrome de Wolf-Parkinson-White, na qual hipertrofia importante e outras anormalidades sistêmicas foram atribuídas à doença mitocondrial.

Comisurotomía percutánea transcateterismo en la estenosis mitral reumática / Percutaneous transcatheter commissurotomy in mitral rheumatic stenosis

La comisurotomía mitral percutánea transcateterismo fué realizada en una paciente del sexo femenino de 11 años de edad. El septum atrial fué atravesado mediante la técnica transeptal y a su través se avanzó un globo-para angioplastía de 8 mm de diámetro. La perforación septal fué luego ampliada para permitir el paso de un catéter de 25 mm para valvuloplastía a través del orificio mitral. El gradiente transmitral postdilatación disminuyó en forma importante de (23 mmHg a 2 mmHg). La reducción del gradiente se asoció a un incremento en el gasto cardíaco (3.4 a 5.3 1t/min). La intensidad del retumbo diatólico disminuyó en forma inmediata después de la dilatación. La comisurotomía transcateterismo no produjo ninguna evidencia de insuficiencia mitral residual. El seguimiento a 5 semanas mostró gradiente trasmitral de 2 mmHg y mejoría clínica definitiva

Septostomia auricular con navaja / Blade atrial septostomy (BAS)

Se describe la experiencia con el primer caso realizado con esta técnica en nuestro país en un pacientes de 3 meses de edad con el diagnóstico de transposición completa de las grandes arterias (TGA), septum interventricular intacto y comunicación interauricular (CIA) restrictiva. El paciente fué sometido a septostomía auricular con balón (SAB) a los 15 días de edad con mejoría transitoria. Por incremento en la cianosis, fué sometido a cateterismo cardíaco, encontrando saturación periférica de 30%, angiográficamente imagen de CIA restrictiva y gradiente transauricular de 2.1 mmHg (aurícula derecha AD: 1.8 y aurícula izquierda AI: 3.9). Se realizaron varios cortes en el septum interauricular con el catéter de septostomía con navaja (SAN) de Park con lo cual las presiones auriculares se elevaron y prácticamente se igualaron (AD: 4.3 y AL: 4.5), con mejoría angiográfica franca del cortocircuito a nivel auricular. La saturación periférica 5 meses después fué de 51.3%. Se describe la técnica, ventajas y complicaciones del procedimiento