The role of BRAF V600E mutation in post-surgical 131I therapy in papillary thyroid carcinoma: a study based on SPECT-CT uptake analysis.

BACKGROUND: The BRAF V600E mutation (BRAF mut) in papillary thyroid cancer (PTC) has been associated with poor response to therapy with 131I in patients with metastases but the results in postsurgical treatment are controversial. Our main objective is to investigate the impact of the mutation on the biokinetics of the administered 131I therapy after surgery. METHODS: A prospective study was designed, from July 2015 to January 2018 which included patients with PTC receiving 131I therapy after surgical treatment. To study the biokinetics of the radioiodine in postoperative thyroid remnants, SPECT-CT images were acquired so as to obtain the following variables: percentage of remnant uptake at 2 and 7 days post-administration, effective half-life and time-integrated activity coefficient. All of them were compared depending on the mutational diagnosis and other clinical features and pathological variables. RESULTS: Sixty-one patients, and in total 103 thyroid remnants, were included. About 59% of patients were BRAF mutated. The mutation was associated with classic variant (88.5% vs. 11.5%; P=0.0001), desmoplastic reaction (85.7% vs. 14.3%; P=0.002), smaller tumor size (1.5 vs. 2.1 cm; P=0.024), nodal disease (3.3 vs. 1; P=0.001) and advanced stages (76.9% vs. 23%; P=0.014). The BRAFmut group had a lower percentage of 131I uptake at 2 days (0.17% vs. 0.47%; P=0.001) and at 7 days (0.02% vs. 0.1%; P=0.013); and a lower time-integrated activity coefficient (0.05h vs. 0.17 h; P=0.002). In univariate analysis, in addition to the mutation, the histological variant was significant but only for time-integrated activity coefficient (P=0.04). In multivariate analysis, only mutation determined the 2-day uptake (P<0.001) and the time-integrated activity coefficient (P<0.001). CONCLUSIONS: The BRAF V600E mutation is associated with lower 131I uptake in thyroid remnants. Furthermore, it is an independent factor that decreases the effect of post-surgical 131I therapy, and therefore, it could be used as a potential tool to optimize the treatment of PTC.

Sentinel lymph node biopsy in papillary thyroid cancer: Accuracy and application in clinical practice.

INTRODUCTION: The presence of lymph nodes metastasis in papillary thyroid cancer (PTC) modifies the type of surgical resection as well as the indication of the treatment with I131 in the postoperative period. This therapeutic approach is based on the results of the diagnostic tests, like the cervical ultrasonography. Currently other methods of diagnostic are tested as selective sentinel lymph node biopsy (SLNB). It can complement to the ultrasound results. The aim was to validate the SLNB for use in the diagnosis of lymph node metastasis by papillary thyroid cancer. METHODS: Observational prospective cohort study of 55 patients who underwent PTC without suspicion of lymph node involvement clinical or radiological, since February 2012 through February 2015, with a follow-up between 6 and 8 years. It was used 99Tc with intratumoral nanocoloid and a portable tube of the gamma camera for the detection of the sentinel node (SN). VARIABLES: age, gender, histological, analytical and preoperative and postoperative staging. The sensitivity, specificity and predictive values of technique was calculated. The validation was determined by calculating the detectability and the false negative results of the test. RESULTS: 53 of the 55 patients (96,36%) there was the SN detection. The FN were 4 patients (7,5%). Of the rest, after applying the SLNB, 24 (48,9%) were kept as N0, 14 (28,5%) became N1a and 11 (22,4%) were classified as N1b. The differences observed in the study were significant (P < ,05). The sensitivity was 86,21%, the specificity of 100%, the PPV was 100% and the NPV of 85.71%. The diagnostic accuracy of 92,45%. CONCLUSION: The SLNB is a valid technique for use in patients suffering from papillary thyroid cancer with a high diagnostic accuracy.

Sentinel lymph node biopsy in papillary thyroid cancer: Accuracy and application in clinical practice. / Ganglio centinela en la metástasis ganglionar por cáncer papilar de tiroides: validez diagnóstica y aplicación en la práctica clínica.

INTRODUCTION: The presence of lymph nodes metastasis in papillary thyroid cancer modifies the type of surgical resection as well as the indication of the treatment with 131I in the postoperative period. This therapeutic approach is based on the results of the diagnostic tests, like the cervical ultrasonography. Currently other methods of diagnostic are tested as selective sentinel lymph node biopsy (SLNB). It can complement to the ultrasound results. The aim was to validate the SLNB for use in the diagnosis of lymph node metastasis by papillary thyroid cancer. METHODS: Observational prospective cohort study of 55 patients who underwent papillary thyroid cancer without suspicion of lymph node involvement clinical or radiological, since February 2012 through February 2015, with a follow-up between 6 and 8 years. It was used 99Tc with intratumoral nanocoloid and a portable tube of the gamma camera for the detection of the sentinel node. VARIABLES: age, gender, histological, analytical and preoperative and postoperative staging. The sensitivity, specificity and predictive values of technique was calculated. The validation was determined by calculating the detectability and the false negative results of the test. RESULTS: In 53 of the 55 patients (96.36%) there was the sentinel node detection. The false negative were 4 patients (7.5%). Of the rest, after applying the SLNB, 24 (48.9%) were kept as N0, 14 (28.5%) became N1a and 11 (22.4%) were classified as N1b. The differences observed in the study were significant (P<.05). The sensitivity was 86.21%, the specificity of 100%, the PPV was 100% and the NPV of 85.71%. The diagnostic accuracy was 92.45%. CONCLUSIONS: The SLNB is a valid technique for use in patients suffering from papillary thyroid cancer with a high diagnostic accuracy.

Mutación del gen BRAF V600E en el cáncer papilar de tiroides y su efecto en la terapia con yodo radiactivo (131I) posquirúrgica: ¿deberíamos modificar nuestra estrategia terapéutica? / BRAF V600E mutation in papillary thyroid cancer and its effect on postoperative radioiodine (131I) therapy: Should we modify our therapeutic strategy?

INTRODUCCIÓN: La mutación BRAF V600E en el cáncer papilar de tiroides (CPT) parece asociarse a una resistencia al 131I. Nuestro principal objetivo fue cuantificar la respuesta al 131I tras la cirugía tanto en pacientes que presentaban la mutación (BRAF+) como en los que no presentaban el gen mutado (BRAF-). MÉTODO: Estudio prospectivo de los CPT intervenidos y tratados con 131I desde septiembre de 2015 hasta enero de 2017. VARIABLES: edad, género, estadio tumoral, histológicas, tiroglobulina antes de 131I, a las 48h y a los 6 meses; dosis absorbida y % de actividad a los 2 y a los 7días y tiempo de eliminación. RESULTADOS: Cuarenta y un pacientes y 67 restos tiroideos. El 61% eran BRAF+. En los estadios III y IV, el 80% eran BRAF+. En el vaciamiento ganglionar terapéutico, el 100% eran BRAF+. El número de ganglios fue superior en BRAF+: 3,4 vs 1,2 (p = 0,01). La variante clásica fue predominante en BRAF+ (91,7% vs 8,3%; p = 0,03). El 85,7% vs 14,3% de los BRAF+ tuvieron reacción desmoplásica (p = 0,02). Los BRAF+ presentaban menor dosis absorbida respecto a la actividad administrada (5,4 vs 20Gy/MBq; p = 0,02); menor % de actividad respecto a la unidad de masa a los 2 (0,046 vs 0,103%/g; p = 0,02) y a los 7 días (0,006 vs 0,034%/g, p = 0,04). CONCLUSIONES: La mutación del gen BRAF V600E se relaciona con una mayor resistencia al tratamiento posquirúrgico con 131I desde el inicio de la enfermedad

INTRODUCTION: The BRAF V600E mutation in papillary thyroid cancer (PTC) has been associated with resistance to 131I. Our aim was to quantify the response to 131I after surgery in patients who had the mutation (BRAF+) and those who did not have the mutated gene (BRAF-). METHOD: A prospective cohort study was designed, from September 2015 to February 2016, which included patients with PTC receiving therapy after surgical treatment. Variables were described for age, gender, histology, tumor stage, thyroglobulin values before, 48 h after and 6months after 131I; absorbed dose and % activity on days 2 and 7 and elimination time. RESULTS: 41 patients giving in total 67 thyroid remnants were included. 61% were BRAF+. In stagesiii and IV, 80% were BRAF+. In lateral resection, 100% were BRAF+. The number of nodes was higher in BRAF+: 3.4 vs 1.2 (P = .01). The classic variant was predominant in BRAF+ (91.7% vs 8.3%, P = .03). 85.7% vs 14.3% of BRAF+ had desmoplastic reaction (P = .02). The BRAF+ had a lower absorbed dose than the administered activity (5.4Gy/MBq vs 20Gy/MBq, P = .02); lower% activity with respect to the unit of mass at 2 (0.046%/g vs 0.103%/g, P = .02) and at 7days (0.006%/gr vs 0.034%/gr, P = .04) CONCLUSIONS: The mutation of the BRAF V600E gene is related with greater resistance to postoperative treatment with 131I since the onset of the disease

BRAF V600E mutation in papillary thyroid cancer and its effect on postoperative radioiodine (131I) therapy: Should we modify our therapeutic strategy? / Mutación del gen BRAF V600E en el cáncer papilar de tiroides y su efecto en la terapia con yodo radiactivo (131I) posquirúrgica: ¿deberíamos modificar nuestra estrategia terapéutica?

INTRODUCTION: The BRAF V600E mutation in papillary thyroid cancer (PTC) has been associated with resistance to 131I. Our aim was to quantify the response to 131I after surgery in patients who had the mutation (BRAF+) and those who did not have the mutated gene (BRAF-). METHOD: A prospective cohort study was designed, from September 2015 to February 2016, which included patients with PTC receiving therapy after surgical treatment. Variables were described for age, gender, histology, tumor stage, thyroglobulin values before, 48h after and 6months after 131I; absorbed dose and % activity on days 2 and 7 and elimination time. RESULTS: 41 patients giving in total 67 thyroid remnants were included. 61% were BRAF+. In stagesiii and iv, 80% were BRAF+. In lateral resection, 100% were BRAF+. The number of nodes was higher in BRAF+: 3.4 vs 1.2 (P=.01). The classic variant was predominant in BRAF+ (91.7% vs 8.3%, P=.03). 85.7% vs 14.3% of BRAF+ had desmoplastic reaction (P=.02). The BRAF+ had a lower absorbed dose than the administered activity (5.4Gy/MBq vs 20Gy/MBq, P=.02); lower% activity with respect to the unit of mass at 2 (0.046%/g vs 0.103%/g, P=.02) and at 7days (0.006%/gr vs 0.034%/gr, P=.04) CONCLUSIONS: The mutation of the BRAF V600E gene is related with greater resistance to postoperative treatment with 131I since the onset of the disease.

Variante anatómica portal como hallazgo casual durante colecistectomía / Portal anatomic variant as an incidental finding during cholecystectomy

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Missed opportunities in early diagnosis of symptomatic colorectal cancer.

OBJECTIVE: delays in diagnosis of symptomatic colorectal cancer are a reality in our context. This study aims at identifying missed diagnostic opportunities, describing events, clinical clues and most common mistakes, and quantifying delays. MATERIAL AND METHODS: an observational descriptive study was performed in order to review all case histories. Two experts reviewed the case histories of all the patients from the 4th Catchment Area of Asturias diagnosed with colorectal cancer in 2009. All data were analysed using bivariate and multivariate logistic regression. RESULTS: full information on 119 patients out of 143 patients was collected. 34.45% had a clinical missed opportunity -confidence interval (CI) 95%: 30.92-39.68-. Outcomes show an average of 2.41 missed opportunities and 2.61 diagnostic clinical clues per patient. The number of patients with missed opportunities was significantly higher. The total amount of co-morbidities was higher in patients with missed opportunities (2.7). This was the main determinant. The main diagnostic key was iron-deficiency anaemia (46.3%). It produced the longest delay (300 days). Not having requested diagnostic tests was the most common mistake (43.3%). Having at least one missed opportunity entailed an average delay of 235.8 days between the first visit to the office and the referral to a consultant. CONCLUSIONS: in clinical practice, missed opportunities to start a diagnostic assessment in patients with presumptive diagnosis of colorectal cancer are common. The most significant clinical clue and the one generating the longest delay is iron-deficiency anaemia. The diagnostic delay is important and is caused mainly by not identifying symptoms.

Oportunidades perdidas en el diagnóstico temprano del cáncer colorrectal sintomático / Missed opportunities in early diagnosis of symptomatic colorectal cancer

Objetivo: los retrasos en el diagnóstico de cáncer colorrectal sintomático son una realidad en nuestro medio. Nos proponemos identificar los casos en los que hubo oportunidad perdida para el diagnóstico, describir las características de los episodios, las claves clínicas, los errores más comunes y cuantificar el retraso generado. Material y métodos: mediante un estudio observacional descriptivo, se procedió a la revisión de las historias clínicas por dos revisores de la totalidad de los pacientes diagnosticados de cáncer colorrectal en el 2009 del Área Sanitaria IV de Asturias. Se analizaron los datos a nivel bivariante y multivariante por regresión logística. Resultados: de 143 se obtuvo información completa de 119 pacientes. Un 34,45% presentó una oportunidad perdida clínica (IC 95%: 30,92-39,68). Hubo una media de 2,41 oportunidades perdidas y 2,61 claves diagnósticas por paciente. Los pacientes con oportunidades perdidas eran significativamente mayores; el número total de comorbilidades resultó ser mayor en los pacientes con oportunidad perdida (2,7) siendo este el factor determinante. La clave diagnóstica principal fue la anemia ferropénica (46,3%) y la que más retraso generó (300 días). El error más común fue la falta de petición de pruebas diagnósticas (43,3%). Tener al menos una oportunidad perdida supuso un retraso promedio de 235,8 días entre el primer encuentro médico-paciente y la derivación a un especialista. Conclusiones: las oportunidades perdidas para iniciar una evaluación diagnóstica en pacientes con sospecha de cáncer colorrectal son frecuentes en la práctica clínica. La clave clínica más relevante y que genera mayor retraso es la anemia ferropénica. El retraso diagnóstico es importante y es debido principalmente al no reconocimiento, o inacción, ante síntomas(AU)

Objective: delays in diagnosis of symptomatic colorectal cancer are a reality in our context. This study aims at identifying missed diagnostic opportunities, describing events, clinical clues and most common mistakes, and quantifying delays. Material and methods: an observational descriptive study was performed in order to review all case histories. Two experts reviewed the case histories of all the patients from the 4th Catchment Area of Asturias diagnosed with colorectal cancer in 2009. All data were analysed using bivariate and multivariate logistic regression. Results: full information on 119 patients out of 143 patients was collected. 34.45% had a clinical missed opportunity -confidence interval (CI) 95%: 30.92-39.68-. Outcomes show an average of 2.41 missed opportunities and 2.61 diagnostic clinical clues per patient. The number of patients with missed opportunities was significantly higher. The total amount of co-morbidities was higher in patients with missed opportunities (2.7). This was the main determinant. The main diagnostic key was iron-deficiency anaemia (46.3%). It produced the longest delay (300 days). Not having requested diagnostic tests was the most common mistake (43.3%). Having at least one missed opportunity entailed an average delay of 235.8 days between the first visit to the office and the referral to a consultant. Conclusions: in clinical practice, missed opportunities to start a diagnostic assessment in patients with presumptive diagnosis of colorectal cancer are common. The most significant clinical clue and the one generating the longest delay is iron-deficiency anaemia. The diagnostic delay is important and is caused mainly by not identifying symptoms(AU)