The potential impact of PCV-13, PCV-15 and PCV-20 vaccines in Colombia.

PURPOSE: To provide information about which pneumococcal vaccine could have greater coverage in Colombia. METHODS: This is a retrospective analysis of patients diagnosed with invasive pneumococcal disease (IPD) between 2015 and 2019 in Bogotá, Colombia. We compared the theoretical serotype coverage of the available anti-pneumococcal vaccines (i.e., PCV-10, PCV-10 SII, PCV-13, PCV-15, PCV-20, PCV-21, PCV24, PPSV-23) and the non-vaccine-covered serotypes stratified by age. RESULTS: 690 IPD cases were included. In children ≤5 y/o, of the approved vaccines PCV-20 showed the most theoretical protection (71.3 % [149/209]), while in adults aged 18-64 y/o was PCV-20 (61.8 % [164/265]), and in those ≥65 y/o was PPSV-23 (58.1 % [100/172]) followed by PCV-20 (55.2 % [95/172]). The non-covered serotypes represented one-third of the cohort (33.9 % [234/690]), being 6C (20.5 % [48/234]), 15A (12.8 % [30/234]), and 23A (11.5 % [27/234]) the most prevalent. CONCLUSION: Introducing PCV-20 for children and PCV-20 along with a PPSV-23 booster in adults may reduce IPD frequency in all ages in Colombia. The inclusion of non-covered serotypes is required for future vaccines.

Prevalence, incidence, and severity associated with viral respiratory tract infections in Colombian adults before the COVID-19 pandemic.

BACKGROUND: Acute respiratory illness (ARI) remains the leading cause of global morbidity. Its primary etiology is viral; nevertheless, viral pathogen identification is limited. Clinical information about Latin America's viral etiology, outcomes, and severity is unknown. This study aims to identify the clinical burden of respiratory viral infections, severity, and adult outcomes. METHODS: This multicentric, population-based study was conducted through the Health Institute of Bogotá, Colombia, including adult patients diagnosed with ARI between 2013 and 2019. Data collection followed ARI public health surveillance program. Incidence, etiological pathogens, and mortality were calculated. RESULTS: A total of 2304 patients were included in the study. ARI was most frequently reported in 2018 (23.3% [538/2304]). Incidence varies between years, maintaining a range between 3.5 and 8.4. The most frequent clinical diagnosis was pneumonia in 59.1%. Etiological viral detection was obtained in 21.5% of patients [495/2304], principally by Influenza A. Mortality was 21.8%, and ICU admission was 7.3%. The type of event did not predict the causative pathogen, disease severity, or mortality. CONCLUSIONS: ARI is a leading cause of morbidity and mortality in Colombia. ARI incidence varies per year and is caused mainly by Influenza A. The classification used in the surveillance program does not correlate with viral etiology, disease severity, and mortality.

Invasive pneumococcal disease burden in hospitalized adults in Bogota, Colombia.

BACKGROUND: The incidence of invasive pneumococcal disease (IPD) varies depending on a number of factors, including vaccine uptake, in both children and adults, the geographic location, and local serotype prevalence. There are limited data about the burden of Streptococcus pneumoniae (Spn), serotype distribution, and clinical characteristics of adults hospitalized due to IPD in Colombia. The objectives of this study included assessment of Spn serotype distribution, clinical characteristics, mortality, ICU admission, and the need for mechanical ventilation. METHODS: This was an observational, retrospective, a citywide study conducted between 2012 and 2019 in Bogotá, Colombia. We analyzed reported positive cases of IPD from 55 hospitals in a governmental pneumococcal surveillance program. Pneumococcal strains were isolated in each hospital and typified in a centralized laboratory. This is a descriptive study stratified by age and subtypes of IPD obtained through the analysis of medical records. RESULTS: A total of 310 patients with IPD were included, of whom 45.5% were female. The leading cause of IPD was pneumonia (60%, 186/310), followed by meningitis. The most frequent serotypes isolated were 19A (13.87%, 43/310) and 3 (11.94%, 37/310). The overall hospital mortality rate was 30.3% (94/310). Moreover, 52.6% (163/310 patients) were admitted to the ICU, 45.5% (141/310) required invasive mechanical ventilation and 5.1% (16/310) non-invasive mechanical ventilation. CONCLUSION: Pneumococcal pneumonia is the most prevalent cause of IPD, with serotypes 19A and 3 being the leading cause of IPD in Colombian adults. Mortality due to IPD in adults continues to be very high.

Burden of invasive pneumococcal disease (IPD) over a 10-year period in Bogotá, Colombia.

BACKGROUND: Invasive pneumococcal disease (IPD) is the leading cause of infectious death worldwide. This study aimed to describe the epidemiology of IPD and the impact of pneumococcal conjugate vaccine-10 (PCV-10) over a 10-year period in Bogotá, Colombia. METHODS: This was a laboratory-based surveillance study of Streptococcus pneumoniae isolated from patients with IPD from 82 hospitals over 10 years in Bogotá, Colombia. Data were compared between two periods: 2007-2011 (before the introduction of PCV-10) and 2012-2017 (after the introduction of PCV-10). RESULTS: In total, 1670 patients with IPD were included in the study between 2007 and 2017. Between 2007 and 2011, the most common serotypes were 14, 1, 6B, 6A and 3. Between 2012 and 2017, the most common serotypes were 19A, 3, 14 and 1. A decrease in the incidence of IPD, particularly in children aged 0-4 years, was noted after the introduction of PCV-10. Importantly, this reduction in incidence was not observed in patients aged ≥50 years. CONCLUSIONS: The IPD burden in Bogotá remained stable between 2007 and 2017. The incidence of IPD decreased in children but not in older adults. The introduction of PCV-10 led to a change in the most prevalent serotypes to serotypes that are not included in PCV-10.

Major Adverse Cardiovascular Events During Invasive Pneumococcal Disease Are Serotype Dependent.

BACKGROUND: Up to 30% of patients admitted to hospitals with invasive pneumococcal disease (IPD) experience major adverse cardiovascular event (MACE) including new/worsening heart failure, new/worsening arrhythmia, and/or myocardial infarction. Streptococcus pneumoniae (Spn) is the most frequently isolated bacterial pathogen among community-acquired pneumonia (CAP) patients and the only etiological agent linked independently to MACE. Nevertheless, no clinical data exist identifying which serotypes of Spn are principally responsible for MACE. METHODS: This was an observational multicenter retrospective study conducted through the Public Health Secretary of Bogotá, Colombia. We included patients with a confirmed clinical diagnosis of IPD with record of pneumococcal serotyping and clinical information between 2012 and 2019. Spn were serotyped using the quellung method by the National Center of Microbiology. MACE were determined by a retrospective chart review. RESULTS: The prevalence of MACE was 23% (71/310) in IPD patients and 28% (53/181) in patients admitted for CAP. The most prevalent S. pneumoniae serotype identified in our study was the 19A, responsible for the 13% (42/310) of IPD in our cohort, of which 21% (9/42) presented MACE. Serotypes independently associated with MACE in IPD patients were serotype 3 (odds ratio [OR] 1, 48; 95% confidence interval [CI] [1.21-2.27]; P = .013) and serotype 9n (OR 1.29; 95% CI [1.08-2.24]; P = .020). Bacteremia occurred in 87% of patients with MACE. Moreover, serum concentrations of C-reactive protein were elevated in patients with MACE versus in non-MACE patients (mean [standard deviation], 138 [145] vs 73 [106], P = .01). CONCLUSIONS: MACE are common during IPD with serotype 3 and 9n independently of frequency.

Encefalitis por anticuerpos contra el receptor de NMDA. Reporte de un caso y revisión de la literatura / Anti-NMDA receptor encephalitis. Case Report and Literature Review / Encefalite causada por anticorpos contra o receptor NMDA. Relatório de caso e revisão da literatura

Resumen: La encefalitis por anticuerpos contra el receptor de NMDA es un desorden grave, tratable y potencialmente reversible, caracterizado por la presencia de alteraciones en el comportamiento, convulsiones y trastornos del movimiento. La presencia de anticuerpos contra el receptor del glutamato (anti-NMDA) en plasma o líquido cefalorraquídeo es específico para el diagnóstico de la enferme -dad. El reconocimiento temprano de la enfermedad es vital para el pronóstico del paciente, dado que el manejo precoz facilita la recuperación y reducción de la morbimortalidad. El tratamiento consiste en la utilización de corticoides, inmunoglobulina intravenosa o plasmaféresis como primera línea de terapia; además de otros inmunomoduladores, como ciclofosfamida o rituximab, como segunda línea. La recuperación es lenta, pero presenta mejoría en la medida en que los títulos de anticuerpos disminuyen y llega a una recuperación completa hasta en 75 % de los pacientes.

Abstract: Anti-NMDA receptor encephalitis is a severe, treatable, and potentially reversible disorder characterized by the presence of behavioral disturbances, seizures, and movement disorders. The presence of antibodies against the glutamate receptor (anti-NMDA) in plasma or cerebrospinal fluid is specific to the diagnosis of the disease. Early recognition of the disease is vital for the patient's prognosis since early management facilitates recovery and reduction of morbidity and mortality. Treatment consists of corticosteroids, intravenous immunoglobulin, or plasmapheresis as the first line of therapy, in addition to other immunomodulators, such as cyclophosphamide or rituximab, as the second line. Recovery is slow but improves as antibody titers decrease. Complete recovery occurs in up to 75 % of patients.

Resumo: A encefalite causada por anticorpos contra o receptor NMDA é um distúrbio grave, tratável e potencialmente reversível, caracterizado pela presença de alterações comportamentais, convulsões e transtornos de movimento. A presença de anticorpos contra o receptor de glutamato (anti-NMDA) no plasma ou no líquido cefalorraquidiano é específica para o diagnóstico da doença. O reconhecimento precoce da doença é vital para o prognóstico do paciente, visto que o tratamento precoce facilita a recuperação e a redução da morbimortalidade. O tratamento consiste no uso de corticoides, imunoglobulina intravenosa ou plasmaférese como primeira linha de terapia. Além de outros imunomoduladores, como ciclofosfamida ou rituximabe, como segunda linha. A recuperação é lenta, mas apresenta melhora à medida que os títulos de anticorpos diminuem e a recuperação completa ocorre em até 75% dos pacientes.

Impacto de la modificación de la exposición a factores de riesgo en la incidencia de cáncer de cavidad oral en Colombia a 2050 / Impact of modification of risk factor prevalence on the incidence of oral cavity cancer in Colombia by the year 2050

Resumen Introducción: En Colombia, en el periodo 2007-2011, se estima que se diagnosticaron alrededor de 1.500 casos de cáncer de cavidad oral y que por esta causa fallecieron 500 personas, en su mayoría eran hombres. La etiología de esta enfermedad está relacionada con el virus del papiloma humano y, el consumo de alcohol y de cigarrillo. Este estudio buscó cuantificar el efecto en la incidencia del cáncer de cavidad oral del cambio hipotético en la prevalencia de factores de riesgo como consumo de alcohol y, de cigarrillo e infección por virus del papiloma humano en Colombia para el periodo 2015-2050. Métodos: Modelo de simulación macro basado en datos secundarios. Resultados: Según los escenarios simulados, al eliminar el consumo de cigarrillo, alcohol e infección por virus del papiloma humano en la población colombiana probablemente sería posible evitar del 27,6% al 82,1% de los casos nuevos de cáncer de cavidad oral en el país en el periodo 2015-2050. Conclusiones: Bajo los supuestos de un escenario basado en las expectativas de la OMS, las estimaciones del modelo elaborado prevé un posible aumento de los casos de cáncer de cavidad oral asociados al consumo de alcohol y un bajo impacto en la prevención con las medidas actuales, por lo que puede ser necesario que se pongan en marcha acciones para disminuir el consumo de alcohol, así como de cigarrillo. Aunque la dirección de los cambios está bien demostrada en los resultados, es importante tener en cuenta que un modelo de simulación depende de muchos supuestos y por ende tiene limitaciones.

Abstract: Introduction: It is estimated that in the period 2007-2011, around 1500 new cases of oral cavity were diagnosed in Colombia, and that around 500 people died of this cause, the majority men. The etiology of this disease is related to the human papilloma virus, alcohol and cigarette use. This study tries to quantify the effect on oral cancer incidence of a hypothetical change in the prevalence of these risk factors in the period 2015-2050. Methods: macrosimulation models based on secondary data. Results: According to the simulated scenarios, elimination of cigarette and alcohol use and elimination of infection by the human papillomavirus in the Colombian population, would probably prevent 27.6 % to 82.1 % of all new cases of oral cavity cancer expected to occur in the period 2015-2050. Conclusions: according to the projections produced by the World Health Organization and the models we specified, there will be a potential increase in the number of new patients diagnosed with oral cavity cancer associated with the use of alcohol and a low impact of the interventions currently in place. It will be necessary to implement measures to descrease alcohol consumption and sustain current efforts to reduce cigarette use. It is important to take into account the limitations of the simulation models.

Neuropatía vasculítica no sistémica: revisión de caso / Non-systemic vasculitic neuropathy: case review / Neuropatia vasculítica não sistêmica: revisão de caso

Resumen La neuropatía vasculítica no sistémica es una condición poco común, caracterizada por el compromiso aislado del sistema nervioso periférico a causa de la infiltración celular en el lecho vascular encargado de su irrigación. Es un término acuñado hace poco más de tres décadas y se considera una enfermedad poco descrita y subdiagnósticada. Se presenta el caso clínico de un paciente masculino de mediana edad que debuta con síntomas progresivos de predominio motor en miembros inferiores, quien es sometido a una serie de estudios que permiten concluir el diagnóstico. Es tratado con corticoides sistémicos, agentes citotóxicos y, por último, agentes biológicos con los que se estabilizaron los síntomas.

Summary Non-systemic vasculitic neuropathy is a rare condition characterized by the isolated involvement of the peripheral nervous system caused by cellular infiltration in the vascular bed responsible for its irrigation. It is a term which was coined a little over three decades ago and is considered a poorly described and underdiagnosed disease. Below, we present the clinical case of a middle-aged male patient who began experiencing progressive symptoms of motor predominance in the lower limbs, and who underwent a series of studies in order to conclude a diagnosis. The patient was treated with systemic corticosteroids, cytotoxic agents and, finally, biological agents which stabilized the symptoms.

Resumo A neuropatia vasculítica não sistêmica é uma condição pouco comum, caracterizada pelo compromisso isolado do sistema nervoso periférico a causa da infiltração celular no leito vascular encarregado de sua irrigação. É um termo cunhado há pouco mais de três décadas e se considera uma doença pouco descrita e subdiagnosticada. A seguir, se apresenta o caso clínico de um paciente masculino de meia idade que debuta com sintomas progressivos de predomínio motor em membros inferiores, que é submetido a uma série de estudos que permitem concluir o diagnóstico. É tratado com corticoides sistêmicos, agentes citotóxicos e, por último, agentes biológicos com o que se estabilizaram os sintomas.

Design, Synthesis and Evaluation of Branched RRWQWR-Based Peptides as Antibacterial Agents Against Clinically Relevant Gram-Positive and Gram-Negative Pathogens.

Multidrug resistance of pathogenic bacteria has become a public health crisis that requires the urgent design of new antibacterial drugs such as antimicrobial peptides (AMPs). Seeking to obtain new, lactoferricin B (LfcinB)-based synthetic peptides as viable early-stage candidates for future development as AMPs against clinically relevant bacteria, we designed, synthesized and screened three new cationic peptides derived from bovine LfcinB. These peptides contain at least one RRWQWR motif and differ by the copy number (monomeric, dimeric or tetrameric) and structure (linear or branched) of this motif. They comprise a linear palindromic peptide (RWQWRWQWR), a dimeric peptide (RRWQWR)2KAhx and a tetrameric peptide (RRWQWR)4K2Ahx2C2. They were screened for antibacterial activity against Enterococcus faecalis (ATCC 29212 and ATCC 51575 strains), Pseudomonas aeruginosa (ATCC 10145 and ATCC 27853 strains) and clinical isolates of two Gram-positive bacteria (Enterococcus faecium and Staphylococcus aureus) and two Gram-negative bacteria (Klebsiella pneumoniae and Pseudomonas aeruginosa). All three peptides exhibited greater activity than did the reference peptide, LfcinB (17-31), which contains a single linear RRWQWR motif. Against the ATCC reference strains, the three new peptides exhibited minimum inhibitory concentration (MIC50) values of 3.1-198.0 µM and minimum bactericidal concentration (MBC) values of 25-200 µM, and against the clinical isolates, MIC50 values of 1.6-75.0 µM and MBC values of 12.5-100 µM. However, the tetrameric peptide was also found to be strongly hemolytic (49.1% at 100 µM). Scanning Electron Microscopy (SEM) demonstrated that in the dimeric and tetrameric peptides, the RRWQWR motif is exposed to the pathogen surface. Our results may inform the design of new, RRWQWR-based AMPs.

In-house standardization and validation of a multiplex RT-PCR assay for the detection of 13 respiratory viruses / Estandarización interna y validación de un ensayo RT-PRC múltiple para la detección de 13 virus respiratorios

Background. Multiplex real time PCR is increasingly used to diagnose respiratory viruses and has shown to be superior to traditional methods, such as culture and antigen detection. Objective. Standardization and validation of a multiplex real-time PCR assay for the detection of 13 respiratory viruses. Methods. The assay was validated using RNA control targets and comparing results to single-target PCR's. Results. Using RNA controls the multiplex format was found to be as sensitive and specific as the single-target PCRs, and no competition was observed between targets. The efficiencies for most of the reactions were approximately 90%, but a lower efficiency was found for Parainfluenza 2 with a rate of amplification in each cycle of 86.63%. On the other hand, a higher efficiency was observed in respiratory syncytial virus A and respiratory syncytial virus B ((93.07% each). Conclusion: This multiplex RT-PCR format shows an adequate efficiency, demonstrating an excellent sensitivity, specificity and repeatability for all the studied respiratory viruses.

Antecedentes. PRC múltiple en tiempo real es usada cada vez más para el diagnóstico de virus respiratorios y ha mostrado ser superior a metodos tradicionales, como cultivo y detección de antígeno. Objetivo. Estandarizar y validar una PRC múltiple en tiempo real para la detección de 13 virus respiratorios. Metodos. El ensayo fue realizado usando blanco de RNA control y comparando los resultados a blancos únicos de PCR. Resultados. Usando el RNA control, el formato de multiplex era tan sensible y específico como la PCR. Las eficiencias para la mayoría de las reacciones de aproximadamente el 90%, pero una eficiencia baja fue encontrada para influenza 2 con una tasa de amplificación en cada ciclo de 86.63%. Por otra parte, una mayor eficiencia fue observada en virus sincitial respitario A y B (93, 67% cada uno). Conclusión. Este formato RT-PCR múltiple muestra una adecuada eficiencia, demostrando un excelente especificidad y reproducibilidad para todos los virus respiratorios estudiados.

Long working hours and health in Europe: Gender and welfare state differences in a context of economic crisis.

This article examines the relationship between moderately long working hours and health status in Europe. A cross-sectional study based on data from the 2010 European Working Conditions Survey (13,518 men and 9381 women) was performed. Working moderately long hours was consistently associated with poor health status and poor psychological wellbeing in countries with traditional family models, in both sexes in Liberal countries and primarily among women in Continental and Southern European countries. A combination of economic vulnerability, increasing labour market deregulation and work overload related to the combination of job and domestic work could explain these findings.

Type-Specific Identification of Genital Human Papillomavirus Infection in Women with Cytological Abnormality.

OBJECTIVES: To estimate the frequency of human papillomavirus (HPV) infection and the genotype distribution of HPV among women with a Pap smear showing atypical squamous cells of undetermined significance (ASC-US) attending the Program for the Detection and Control of Cervical Cancer in Bogotá, Colombia. STUDY DESIGN: Cervical samples from 200 women with an ASC-US Pap smear were analyzed for the presence of HPV DNA and genotype distribution using a commercial molecular technique (Linear Array®; Roche Molecular Systems, USA). RESULTS: HPV infection was found in 140 women (70%). High-risk HPV types were present in 46.4% of the samples; 16.4% showed a low-risk HPV type, and 37.1% showed both. Of the positive samples, 42.9% were infected with a single viral genotype, whereas 57.1% exhibited multiple HPV infections. The most common HPV genotypes were HPV 16, 53, and 52 with a prevalence of 26.4, 16.4, and 13.6%, respectively. CONCLUSION: The epidemiological characterization of HPV infections described in this study might guide actions for epidemiological surveillance to strengthen the program in Bogotá and to develop appropriate HPV vaccination programs.

Was access to health care easy for immigrants in Spain? The perspectives of health personnel in Catalonia and Andalusia.

Until April 2012, all Spanish citizens were entitled to health care and policies had been developed at national and regional level to remove potential barriers of access, however, evidence suggested problems of access for immigrants. In order to identify factors affecting immigrants' access to health care, we conducted a qualitative study based on individual interviews with healthcare managers (n=27) and professionals (n=65) in Catalonia and Andalusia, before the policy change that restricted access for some groups. A thematic analysis was carried out. Health professionals considered access to health care "easy" for immigrants and similar to access for autochthons in both regions. Clear barriers were identified to enter the health system (in obtaining the health card) and in using services, indicating a mismatch between the characteristics of services and those of immigrants. Results did not differ among regions, except for in Catalonia, where access to care was considered harder for users without a health card, due to the fees charged, and in general, because of the distance to primary health care in rural areas. In conclusion, despite the universal coverage granted by the Spanish healthcare system and developed health policies, a number of barriers in access emerged that would require implementing the existing policies. However, the measures taken in the context of the economic crisis are pointing in the opposite direction, towards maintaining or increasing barriers.

Viral Infection in Adults with Severe Acute Respiratory Infection in Colombia.

OBJECTIVES: To identify the viral aetiology in adult patients with severe acute respiratory infection (SARI) admitted to sentinel surveillance institutions in Bogotá in 2012. DESIGN: A cross-sectional study was conducted in which microarray molecular techniques for viral identification were used on nasopharyngeal samples of adult patients submitted to the surveillance system, and further descriptions of clinical features and relevant clinical outcomes, such as mortality, need for critical care, use of mechanical ventilation and hospital stay, were obtained. SETTING: Respiratory infections requiring hospital admission in surveillance centres in Bogotá, Colombia. PARTICIPANTS: Ninety-one adult patients with acute respiratory infection (55% were female). MEASUREMENTS: Viral identification, intensive care unit admission, hospital stay, and mortality. RESULTS: Viral identification was achieved for 63 patients (69.2%). Comorbidity was frequently identified and mainly involved chronic pulmonary disease or pregnancy. Influenza, Bocavirus and Adenovirus were identified in 30.8%, 28.6% and 18.7% of the cases, respectively. Admission to the intensive care unit occurred in 42.9% of the cases, while mechanical ventilation was required for 36.3%. The average hospital stay was 9.9 days, and mortality was 15.4%. Antibiotics were empirically used in 90.1% of patients. CONCLUSIONS: The prevalence of viral aetiology of SARI in this study was high, with adverse clinical outcomes, intensive care requirements and high mortality.

Immunomodulation by imiquimod in patients with high-risk primary melanoma.

Imiquimod is a synthetic Toll-like receptor 7 (TLR7) agonist approved for the topical treatment of actinic keratoses, superficial basal cell carcinoma, and genital warts. Imiquimod leads to an 80-100% cure rate of lentigo maligna; however, studies of invasive melanoma are lacking. We conducted a pilot study to characterize the local, regional, and systemic immune responses induced by imiquimod in patients with high-risk melanoma. After treatment of the primary melanoma biopsy site with placebo or imiquimod cream, we measured immune responses in the treated skin, sentinel lymph nodes (SLNs), and peripheral blood. Treatment of primary melanomas with 5% imiquimod cream was associated with an increase in both CD4+ and CD8+ T cells in the skin, and CD4+ T cells in the SLN. Most of the CD8+ T cells in the skin were CD25 negative. We could not detect any increases in CD8+ T cells specifically recognizing HLA-A(*)0201-restricted melanoma epitopes in the peripheral blood. The findings from this small pilot study demonstrate that topical imiquimod treatment results in enhanced local and regional T-cell numbers in both the skin and SLN. Further research into TLR7 immunomodulating pathways as a basis for effective immunotherapy against melanoma in conjunction with surgery is warranted.

Axillary recurrence after sentinel lymph node biopsy for breast cancer.

Sentinel lymph node biopsy (SLNB) is routinely performed as an axillary staging procedure for breast cancer. Although the reported false-negative rate approaches 10 per cent, this does not always lead to axillary recurrence. We previously reported an axillary recurrence rate of 1 per cent at a median follow-up of 2 years. Our objective is to determine the rate of axillary recurrence with longer follow-up. A retrospective review of patients with invasive breast cancer and a negative SLNB treated between 2001 and 2005 was performed. Cases where neoadjuvant therapy was used or where isolated tumor cells (ITCs) were found were included, whereas those with fewer than 18 months of follow-up were excluded. One (0.7%) out of 139 patients had an axillary recurrence after a median follow-up of 52 months. No patient who underwent neoadjuvant chemotherapy or with ITCs had axillary recurrence. Twelve (8.6%) patients have died, with death attributed to breast cancer in three. Our study demonstrates that axillary recurrence after SLNB remains a rare event after a median follow-up of 52 months, despite including potentially higher risk scenarios such as where neoadjuvant chemotherapy is used and ITCs are found. Therefore, axillary lymph node dissection can safely be avoided in patients where SLNB is negative.

Focused microwave thermotherapy for preoperative treatment of invasive breast cancer: a review of clinical studies.

BACKGROUND: Preoperative focused microwave thermotherapy (FMT) is a promising method for targeted treatment of breast cancer cells. Results of four multi-institutional clinical studies of preoperative FMT for treating invasive carcinomas in the intact breast are reviewed. METHODS: Externally applied wide-field adaptive phased-array FMT has been investigated both as a preoperative heat-alone ablation treatment and as a combination treatment with preoperative anthracycline-based chemotherapy for breast tumors ranging in ultrasound-measured size from 0.8 to 7.8 cm. RESULTS: In phase I, eight of ten (80%) patients receiving a single low dose of FMT prior to receiving mastectomy had a partial tumor response quantified by either ultrasound measurements of tumor volume reduction or by pathologic cell kill. In phase II, the FMT thermal dose was increased to establish a threshold dose to induce 100% pathologic tumor cell kill for invasive carcinomas prior to breast-conserving surgery (BCS). In a randomized study for patients with early-stage invasive breast cancer, of those patients receiving preoperative FMT at ablative temperatures, 0 of 34 (0%) patients had positive tumor margins, whereas positive margins occurred in 4 of 41 (9.8%) of patients receiving BCS alone (P = 0.13). In a randomized study for patients with large tumors, based on ultrasound measurements the median tumor volume reduction was 88.4% (n = 14) for patients receiving FMT and neoadjuvant chemotherapy, compared with 58.8% (n = 10) reduction in the neoadjuvant chemotherapy-alone arm (P = 0.048). CONCLUSIONS: Wide-field adaptive phased-array FMT can be safely administered in a preoperative setting, and data from randomized studies suggest both a reduction in positive tumor margins as a heat-alone treatment for early-stage breast cancer and a reduction in tumor volume when used in combination with anthracycline-based chemotherapy for patients with large breast cancer tumors. Larger randomized studies are required to verify these conclusions.