Active surveillance is a feasible and safe strategy in selected patients with papillary thyroid cancer and suspicious cervical lymph nodes detected after thyroidectomy.

Objective: After initial treatment, up to 30% of patients with papillary thyroid cancer (PTC) have incomplete response, mainly cervical lymph node (LN) disease. Previous studies have suggested that active surveillance (AS) is a possible option for these patients. Our aim was to report the results of AS in patients with PTC and cervical LN disease. Materials and methods: In this retrospective observational study, we included adult patients treated and followed for PTC, who presented with cervical LN disease and were managed with AS. Growth was defined as an increase ≥ 3mm in either diameter. Results: We included 32 patients: 27 (84.4%) women, age of 39 ± 14 years, all initially treated with total thyroidectomy, and 22 (69%) with therapeutic neck dissection. Cervical LN disease was diagnosed 1 year (0.3-12.6) after initial management, with a diameter of 9.0 mm (6.0-19.0). After a median AS of 4.3 years (0.6-14.1), 4 (12.5%) patients had LNgrowth: 2 (50%) of whom were surgically removed, 1 (25%) was effectively treated with radiotherapy, and 1 (25%) had a scheduled surgery. Tg increase was the only predictive factor of LN growth evaluated as both the delta Tg (p < 0.0366) and percentage of Tg change (p < 0.0140). None of the included patients died, had local complications due to LN growth or salvage therapy, or developed distant metastases during follow-up. Conclusion: In selected patients with PTC and suspicious cervical LNs diagnosed after initial treatment, AS is a feasible and safe strategy as it allows effective identification and treatment of the minority of patients who progress.

Rewiring Saccharomyces cerevisiae metabolism for optimised Taxol® precursors production.

Saccharomyces cerevisiae has been conveniently used to produce Taxol® anticancer drug early precursors. However, the harmful impact of oxidative stress by the first cytochrome P450-reductase enzymes (CYP725A4-POR) of Taxol® pathway has hampered sufficient progress in yeast. Here, we evolved an oxidative stress-resistant yeast strain with three-fold higher titre of their substrate, taxadiene. The performance of the evolved and parent strains were then evaluated in galactose-limited chemostats before and under the oxidative stress by an oxidising agent. The interaction of evolution and oxidative stress was comprehensively evaluated through transcriptomics and metabolite profiles integration in yeast enzyme-constrained genome scale model. Overall, the evolved strain showed improved respiration, reduced overflow metabolites production and oxidative stress re-induction tolerance. The cross-protection mechanism also potentially contributed to better heme, flavin and NADPH availability, essential for CYP725A4 and POR optimal activity in yeast. The results imply that the evolved strain is a robust cell factory for future efforts towards Taxol© production.

Molecular basis of progressive familial intrahepatic cholestasis 3. A proteomics study.

Progressive familial intrahepatic cholestasis type 3 (PFIC3) is a severe rare liver disease that affects between 1/50,000 and 1/100,000 children. In physiological conditions, bile is produced by the liver and stored in the gallbladder, and then it flows to the small intestine to play its role in fat digestion. To prevent tissue damage, bile acids (BAs) are kept in phospholipid micelles. Mutations in phosphatidyl choline transporter ABCB4 (MDR3) lead to intrahepatic accumulation of free BAs that result in liver damage. PFIC3 onset usually occurs at early ages, progresses rapidly, and the prognosis is poor. Currently, besides the palliative use of ursodeoxycholate, the only available treatment for this disease is liver transplantation, which is really challenging for short-aged patients. To gain insight into the pathogenesis of PFIC3 we have performed an integrated proteomics and phosphoproteomics study in human liver samples to then validate the emerging functional hypotheses in a PFIC3 murine model. We identified 6246 protein groups, 324 proteins among them showing differential expression between control and PFIC3. The phosphoproteomic analysis allowed the identification of 5090 phosphopeptides, from which 215 corresponding to 157 protein groups, were differentially phosphorylated in PFIC3, including MDR3. Regulation of essential cellular processes and structures, such as inflammation, metabolic reprogramming, cytoskeleton and extracellular matrix remodeling, and cell proliferation, were identified as the main drivers of the disease. Our results provide a strong molecular background that significantly contributes to a better understanding of PFIC3 and provides new concepts that might prove useful in the clinical management of patients.

A Prospective Double-Blinded Comparison of Reflectance Confocal Microscopy with Conventional Histopathology for In Vivo Assessment in Oral Cancer.

PURPOSE: We investigated reflectance confocal microscopy (RCM) as a possible noninvasive approach for the diagnosis of cancer and real-time assessment of surgical margins. EXPERIMENTAL DESIGN: In a phase I study on 20 patients, we established the RCM imaging morphologic features that distinguish oral squamous cell carcinoma (OSCC) from normal tissue with a newly developed intraoral RCM probe. Our subsequent phase II prospective double-blinded study in 60 patients tested the diagnostic accuracy of RCM against histopathology. Five RCM videos from the tumor and five from normal surrounding mucosa were collected on each patient, followed by a 3-mm punch biopsy of the imaged area. An experienced RCM reader, who was blinded to biopsy location and histologic diagnosis, examined the videos from both regions and classified each as "tumor" or "not tumor" based on RCM features established in phase I. Hematoxylin and eosin slides from the biopsies were read by a pathologist who was blinded to RCM results. Using histology as the gold standard, we calculated the sensitivity and specificity of RCM. RESULTS: We report a high agreement between the blinded readers (95% for normal tissue and 81.7% for tumors), high specificity (98.3%) and negative predictive values (96.6%) for normal tissue identification, and high sensitivity (90%) and positive predictive values (88.2%) for tumor detection. CONCLUSIONS: RCM imaging is a promising technology for noninvasive in vivo diagnosis of OSCC and for real-time intraoperative evaluation of mucosal surgical margins. Its inherent constraint, however, stems from the diminished capability to evaluate structures located at more substantial depths within the tissue.

Lobectomy in patients with differentiated thyroid cancer: experience of a Chilean tertiary center.

PURPOSE: Thyroid lobectomy (TL) is an appropriate treatment for up to 4 cm intrathyroidal differentiated thyroid cancer (DTC). There is scarce data regarding TL outside first-world centers. Our aim is to report a cohort of patients with DTC treated with TL in Chile. METHODS: We included DTC patients treated with TL, followed for at least 6 months, characterized their clinicopathological features and classified their risk of recurrence and response to treatment. RESULTS: Eighty-two patients followed for a median of 2.3 years (0.5-7.0). Seventy-three (89%) patients had papillary, 8 (9.8%) follicular and 1 (1.2%) high-grade DTC. The risk of recurrence was low in 56 (68.3%) and intermediate in 26 (31.7%). Eight (9.8%) patients required early completion thyroidectomy and radioiodine. At last follow-up, 52 (70.3%) had excellent, 19 (25.7%) had indeterminate, and 1 (1.4%) had structural incomplete response. CONCLUSION: In a developing country, TL is an adequate option for appropriately selected DTC patients.

Latin American Consensus on the Treatment of Head and Neck Cancer.

Head and neck squamous cell carcinoma (HNSCC) is well known as a serious health problem worldwide, especially in low-income countries or those with limited resources, such as most countries in Latin America. International guidelines cannot always be applied to a population from a large region with specific conditions. This study established a Latin American guideline for care of patients with head and neck cancer and presented evidence of HNSCC management considering availability and oncologic benefit. A panel composed of 41 head and neck cancer experts systematically worked according to a modified Delphi process on (1) document compilation of evidence-based answers to different questions contextualized by resource availability and oncologic benefit regarding Latin America (region of limited resources and/or without access to all necessary health care system infrastructure), (2) revision of the answers and the classification of levels of evidence and degrees of recommendations of all recommendations, (3) validation of the consensus through two rounds of online surveys, and (4) manuscript composition. The consensus consists of 12 sections: Head and neck cancer staging, Histopathologic evaluation of head and neck cancer, Head and neck surgery-oral cavity, Clinical oncology-oral cavity, Head and neck surgery-oropharynx, Clinical oncology-oropharynx, Head and neck surgery-larynx, Head and neck surgery-larynx/hypopharynx, Clinical oncology-larynx/hypopharynx, Clinical oncology-recurrent and metastatic head and neck cancer, Head and neck surgery-reconstruction and rehabilitation, and Radiation therapy. The present consensus established 48 recommendations on HNSCC patient care considering the availability of resources and focusing on oncologic benefit. These recommendations could also be used to formulate strategies in other regions like Latin America countries.

Ultrasound evaluation of diaphragm function in patients with cervical spinal cord injury: case report

Abstract Ultrasound evaluation of diaphragm function allows the detection of diaphragm dysfunction and the adaptation of ventilatory support in patients admitted to intensive care units. The studied patient had a C3 spinal cord injury. Ultrasound evaluation of diaphragm mobility showed that the patient suffered diaphragm dysfunction. A tracheotomy was indicated, and early ventilatory support was initiated. Ultrasound evaluation of diaphragm function in patients with cervical spinal cord injury is a useful and simple technique. It provides fast and reliable data for the diagnosis of respiratory insufficiency of neuromuscular origin.

Active surveillance is a feasible and safe strategy in selected patients with papillary thyroid cancer and suspicious cervical lymph nodes detected after thyroidectomy

ABSTRACT Objective: After initial treatment, up to 30% of patients with papillary thyroid cancer (PTC) have incomplete response, mainly cervical lymph node (LN) disease. Previous studies have suggested that active surveillance (AS) is a possible option for these patients. Our aim was to report the results of AS in patients with PTC and cervical LN disease. Materials and methods: In this retrospective observational study, we included adult patients treated and followed for PTC, who presented with cervical LN disease and were managed with AS. Growth was defined as an increase ≥ 3mm in either diameter. Results: We included 32 patients: 27 (84.4%) women, age of 39 ± 14 years, all initially treated with total thyroidectomy, and 22 (69%) with therapeutic neck dissection. Cervical LN disease was diagnosed 1 year (0.3-12.6) after initial management, with a diameter of 9.0 mm (6.0-19.0). After a median AS of 4.3 years (0.6-14.1), 4 (12.5%) patients had LN growth: 2 (50%) of whom were surgically removed, 1 (25%) was effectively treated with radiotherapy, and 1 (25%) had a scheduled surgery. Tg increase was the only predictive factor of LN growth evaluated as both the delta Tg (p < 0.0366) and percentage of Tg change (p < 0.0140). None of the included patients died, had local complications due to LN growth or salvage therapy, or developed distant metastases during follow-up. Conclusions: In selected patients with PTC and suspicious cervical LNs diagnosed after initial treatment, AS is a feasible and safe strategy as it allows effective identification and treatment of the minority of patients who progress.

Bloqueo de nervio mentoniano para braquiterapia de carcinoma de labio / Mental nerve block for brachytherapy of lip carcinoma

Introducción: El cáncer de labio es el tumor más frecuente de la cavidad oral que afecta, sobre todo, el labio inferior. La braquiterapia es un tratamiento único eficaz en estadios tempranos y como terapia adyuvante a la cirugía en estadios avanzados. Esta técnica es un proceso doloroso por lo que para su realización se han empleado sedaciones profundas, infiltraciones intramusculares de anestésico local y técnicas de anestesia regional, entre otras. Objetivo: Presentar una técnica anestésica diferente y poco descrita como alternativa para disminuir el dolor de la intervención. Presentación del caso: Paciente con carcinoma de labio programado para braquiterapia. Se realiza bloqueo del nervio mentoniano de manera bilateral para el tratamiento en labio inferior. Conclusiones: Este tipo de bloqueo, por su sencillez y eficacia, es una alternativa útil a la sedación profunda para la realización de braquiterapia en el labio inferior(AU)

Introduction: Lip cancer is the most frequent tumor of the oral cavity that affects, above all, the lower lip. Brachytherapy is a unique treatment which is effective in early stages and, as adjuvant therapy to surgery, it is also effective in advanced stages. This technique is a painful process, a reason why deep sedation, intramuscular infiltrations of local anesthetic, and regional anesthesia techniques, among others, have been used. Objective: To present a different and scarcely described anesthetic technique as an alternative to reduce the pain of this intervention. Case presentation: Patient with lip carcinoma scheduled for brachytherapy. Bilateral mental nerve block is performed in the lower lip. Conclusions: This type of block, due to its simplicity and effectiveness, is a useful alternative to deep sedation for brachytherapy in the lower lip(AU)

Warthin-like and classic papillary thyroid cancer have similar clinical presentation and prognosis

ABSTRACT Objective Warthin-like papillary thyroid cancer (WL-PTC) is an uncommon variant of PTC, usually associated with lymphocytic thyroiditis. Scarce evidence suggests that WL-PTC has similar clinical presentation to classic PTC (C-PTC), with no studies comparing risks of recurrence and response to treatment between both variants. Our objective was to describe the clinical presentation and prognosis of WL-PTC and compare it to C-PTC. Subjects and methods Retrospective analysis of a prospective cohort, including 370 (96%) patients with C-PTC and 17 (4%) with WL-PTC, consecutively treated with total thyroidectomy with or without RAI, followed for at least 6 months. We compared clinical presentation, risk of mortality and recurrence, as well as response to treatment between both variants. Results Of the total cohort: 317 (82%) female, 38 ± 13.5 years, median follow-up 4 years (0.5-28.5); most of them stage I and low/intermediate risk of recurrence. We found no differences regarding clinical-pathological data and risk of recurrence. WL-PTC was associated with a higher rate of anti-thyroglobulin antibodies (TgAb) (65% vs. 36%, p = 0.016) and lymphocytic thyroiditis (59% vs. 34%, p = 0.03). The rates of biochemical and structural incomplete responses were similar in both variants. WL-PTC had a lower rate of excellent response (23% vs. 54%, p = 0.01), which became non-significant when performing analysis by TgAb presence (50% vs. 67%, p = NS). Conclusions WL-CPT and C-CPT have similar clinical presentation and rate of recurrence. The lower rate of excellent response to treatment in WL-PTC is due to a higher frequency of TgAb. WL-PCT should not be considered an aggressive variant of PTC.

Manejo de nódulos tiroideos y cáncer de tiroides con lobectomía: experiencia de un equipo multidisciplinario / Management of thyroid nodules and thyroid cancer with lobectomy: experience of a multidisciplinary team

INTRODUCCIÓN: La extensión de la cirugía es motivo de controversia en el manejo de nódulos y cáncer diferenciado de tiroides (CDT). En nódulos benignos e indeterminados que requieran cirugía, la lobectomía es de elección, mientras que en CDT debe considerarse en tumores intratiroideos ≤ 4 cm. NUESTRO OBJETIVO objetivo fue reportar la primera cohorte chilena de nódulos tiroideos y CDT tratados con lobectomía por un equipo multidisciplinario. SUJETOS Y MÉTODOS: Se incluyeron pacientes sometidos a lobectomía por nódulos tiroideos y CDT que cumplieran: 1) tumor intratiroideo ≤4cm si punción aspirativa (PAF) Bethesda I, III, IV, V o VI; sin límite de tamaño si PAF Bethesda II, y 2) sin hallazgos sospechosos en la ecografía preoperatoria. En pacientes con CDT se describió presentación clínica, complicaciones y tipo de respuesta a tratamiento según ATA 2015 y MINSAL 2020. RESULTADOS: Se incluyeron 105 pacientes, edad 38±11 años, 84 (80%) mujeres, diámetro 2,2±1,5cm: 41 (39%) benignos y 64 (61%) CDT. De los CDT, 44 (69%) tenían cáncer papilar, 7 (11%) cáncer folicular y 13 (20%) NIFTP. Todos eran etapa I. Según MINSAL, 55 (85,9%) de riesgo muy bajo/bajo y 9 (14,1%) intermedio. Según ATA, 51 (80%) y 13 (20%) de riesgo bajo e intermedio, respectivamente. Se indicó totalización precoz y ablación con radioyodo en 6 (9,4%) pacientes: 4 por invasión venosa y 2 por CPT variedad sólida. De los 39 no totalizados seguidos ≥6 meses, no hubo casos de respuesta incompleta. Respecto a las complicaciones, ningún paciente tuvo hipocalcemia y 10 (9,5%) tuvieron disfonía transitoria. CONCLUSIONES: En pacientes con nódulos tiroideos o CDT seleccionados, la lobectomía es una alternativa adecuada. En CDT logra buen control de enfermedad sin necesidad de tratamiento adicional en cerca de 90% de los pacientes, con muy baja morbilidad asociada.

INTRODUCTION: The extension of surgery is a matter of debate in the management of thyroid nodules and differentiated thyroid cancer (DTC). While lobectomy is the procedure of choice in benign and indeterminate nodules that require surgery, it is an option in intrathyroidal DTC up to 4 cm. OUR OBJECTIVE was to report the first Chilean cohort of patients with thyroid nodules and DTC treated with lobectomy by a multidisciplinary team. SUBJECTS AND METHODS: We included patients with thyroid nodules treated with lobectomy, who met the following inclusion criteria: 1) intrathyroidal tumor ≤ 4cm if fine-needle aspiration biopsy (FNA) was Bethesda I, III, IV, V o VI; without size limit if FNA was Bethesda II, and 2) non-suspicious findings in preoperative ultrasound. In patients with DTC we described clinical presentation, complications and response to treatment according to ATA 2015 and MINSAL 2020. RESULTS: We included 105 patients, 38±11 years old, 84 (80%) female, diameter 2.2±1.5cm: 41 (39%) benign and 64 (61%) DTC. Among DTC, 44 (69%) had papillary thyroid cancer, 7 (11%) follicular thyroid cancer and 13 (20%) NIFTP. All had stage I DTC. According to MINSAL, 55 (85.9%) were very low/low, and 9 (14.1%) intermediate risk. According to ATA, 51 (80%) and 13 (20%) were low and intermediate risk, respectively. Six (9.4%) patients required early completion thyroidectomy and radioiodine ablation: 4 due to angioinvasion and 2 due to solid variant PTC. None of the 39 non-completed patients followed for at least 6 months had incomplete response. Regarding complications, there were no cases of hypocalcemia and 10 (9.5%) patients had transient dysphonia. CONCLUSIONS: In properly selected patients with thyroid nodules or DTC, lobectomy is an appropriate treatment option. In DTC, lobectomy accomplishes adequate disease control without need of further treatment in nearly 90% of patients, with very low associated morbidity.

Aspectos epidemiológicos del virus de inmunodeficiencia humana en costa rica / Epidemiological Aspects of the human immunodeficiency virus in Costa Rica

Resumen El virus de la imnumodeficiencia humana realizo el salto interespecie hace ya más de 100 años de los monos hacia los humanos, produciendo dos tipos de virus capaces de infectar al ser humano, el virus de la inmunodeficiencia humana tipo 1 y el tipo 2. Estos se han diseminado desde África al resto del mundo por diversas vías, llegando a Costa Rica en los años 80. Y desde entonces se han producido con cada año que pasa más casos nuevos, siendo el número de personas infectadas cada vez mayor que en el año anterior estudiado, sin hasta el momento poder frenar la diseminación del virus a pesar de los métodos de prevención existentes.

Abstract The Human Immunodeficiency Virus take an interspecie jump more than 100 years ago from the monkeys to the humans, by transforming into two types of viruses capable to infect the human being, the human immunodeficiency virus Type1 and type 2. This type of virus have spread from Africa to the rest of the world by different ways, arriving to Costa Rica in the 80´s. Since the arrival of the virus, every year, there have been reported more new cases, than the last year studied, and the efforts in prevention to stop the spread of the disease show no results.

Diagnóstico ecográfico de la insuficiencia respiratoria postoperatoria aguda tras timectomía / Role of ecography in diagnostic of postoperative acute respiratory failure after timectomy / Diagnóstico ultrassonográfico da insuficiência respiratória aguda pós-operatória após timectomia

Resumen: La miastenia gravis es una enfermedad autoinmune que puede alterar las capacidades físicas de los pacientes. La timectomía es una de las opciones terapéuticas. Su postoperatorio puede ser complicado por la propia enfermedad o por lesiones intraoperatorias de estructuras nerviosas. Presentamos a una mujer de 66 años intervenida de timectomía por timoma que causa miastenia gravis. Durante la intervención se reseca el nervio frénico izquierdo. En el postoperatorio inmediato presenta insuficiencia respiratoria aguda, por lo que se realiza ecografía pulmonar anodina y ecografía diafragmática que muestra fracción de acortamiento de 10% en el lado derecho y ausencia de contractilidad en el lado izquierdo. La paciente precisó ventilación mecánica no invasiva durante seis días y traqueotomía para avanzar en el destete respiratorio, siendo dada de alta a planta finalmente en respiración espontánea con cánula fenestrada por traqueotomía. La ecografía diafragmática supone una técnica diagnóstica disponible a la cabecera del paciente, útil en situaciones urgentes gracias a su rápida realización y a que complementa la valoración clínica en el diagnóstico de la insuficiencia respiratoria aguda postquirúrgica.

Abstract: Myasthenia gravis is an autoimmune disease that can alter the physical abilities of patients. Thymectomy is one of the therapeutic options. The postoperatory may be complicated by the disease itself or by intraoperative lesions of nerve structures. Case of 66-year-old woman with myasthenia gravis undergoing thymectomy. The left phrenic nerve was resected. In the immediate postoperative period, the patient presented acute respiratory failure. A lung ultrasound is performed, being anodyne. The diaphragmatic ultrasound proved a 10% of thickening fraction on the right side and absence of contractility on the left side. The patient required non-invasive mechanical ventilation for six days, tracheotomy was performed to succeed the respiratory weaning. The patient was transferred to ward in spontaneous ventilation. The diaphragmatic ultrasound is a useful and portable diagnostic technique, mainly in urgent situations due to the rapidity of its implementation. It complements the clinical assessment in the diagnosis of acute postoperative respiratory failure.

Resumo: A miastenia gravis é uma doença auto-imune que pode alterar as capacidades físicas dos pacientes. A timectomia é uma das opções de tratamento. O pós-operatório pode ser complicado pela própria doença ou por lesões intra-operatória de estruturas nervosas. Apresentamos uma mulher de 66 anos submetida a timectomia por timoma que causa miastenia gravis. Durante a cirurgia, o nervo frênico esquerdo é ressecado. No pós-operatório imediato, a paciente apresentou insuficiência respiratória aguda, de modo que foram realizadas uma ultrassonografia pulmonar anódino e ecografia diafragmática, mostrando uma fração de encurtamento de 10% no lado direito e ausência de contratilidade no lado esquerdo. A paciente requeriu de ventilação mecânica não invasiva por 6 dias e a realização de uma traqueotomia para avançar no desmame respiratório, sendo dada de alta da UTI respirando espontâneamente com uma cânula de traqueostomia fenestrada. O ultrassom diafragmático é uma técnica de diagnóstico disponível à beira do leito, útil em situações urgentes devido à rapidez do seu desempenho e que complementa a avaliação clínica no diagnóstico de insuficiência respiratória aguda pós-operatória.

The burden of cancer in Mexico, 1990-2013 / La carga del cáncer en México, 1990-2013

Abstract: Objective: To analyze mortality and incidence for 28 cancers by deprivation status, age and sex from 1990 to 2013. Materials and methods: The data and methodological approaches provided by the Global Burden of Disease (GBD 2013) were used. Results: Trends from 1990 to 2013 show important changes in cancer epidemiology in Mexico. While some cancers show a decreasing trend in incidence and mortality (lung, cervical) others emerge as relevant health priorities (prostate, breast, stomach, colorectal and liver cancer). Age standardized incidence and mortality rates for all cancers are higher in the northern states while the central states show a decreasing trend in the mortality rate. The analysis show that infection related cancers like cervical or liver cancer play a bigger role in more deprived states and that cancers with risk factors related to lifestyle like colorectal cancer are more common in less marginalized states. Conclusions: The burden of cancer in Mexico shows complex regional patterns by age, sex, types of cancer and deprivation status. Creation of a national cancer registry is crucial.

Resumen: Objetivo: Analizar la incidencia y la mortalidad de 28 tipos de cáncer por nivel de marginación, grupos de edad y sexo, de 1990 a 2013. Material y métodos: Los datos utilizados provienen del estudio de la Carga Global de Enfermedades (2013). Las entidades federativas se clasificaron de acuerdo con el índice de marginación del Consejo Nacional de Población. Resultados: Los datos muestran una tendencia decreciente para algunos cánceres (pulmón y cervical), mientras otros aparecen como prioritarios y relevantes (próstata, mama, estómago, colon e hígado). En el norte se observan incrementos regionales mayores en las tasas de incidencia y mortalidad estandarizadas por edad, mientras que en los estados del centro se observa una tendencia decreciente de la tasa de mortalidad. Conclusiones: La epidemiología del cáncer en México (en su mayoría basada en datos de mortalidad) presentan patrones regionales complejos por edad, sexo, tipo de cáncer e índice de marginación. Es vital la creación de un registro nacional para mejorar el seguimiento y evaluación de intervenciones preventivas y curativas.