Morbilidad relacionada con el momento de la linfadenectomía por afectación del ganglio centinela en el melanoma: Una puntualización a su evidencia / Morbidity Associated With the Timing of Lymphadenectomy for Sentinel Lymph Node Metastasis in Melanoma: A Clarification Concerning the Available Evidence

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Mitotic rate as an important prognostic factor in cutaneous malignant melanoma.

BACKGROUND: Recently, the quantification of mitoses in cutaneous melanoma has been discharged from the main prognostic variables of the TNM classification. OBJECTIVE: To investigate the prognostic value of the presence of mitoses in primary cutaneous melanoma and to establish the number of mitoses per mm2 that may have prognostic significance. METHODS: A retrospective observational study was performed on 141 patients treated for cutaneous melanoma, who were assessed by the same pathologist, and who had a minimum follow-up of 2 years. Clinical, epidemiological, histopathological and follow-up variables were gathered and compared with the number of mitoses to distinguish the significance of differences by means of univariate, multivariate, and survival analyses. RESULTS: The cut-off level related to a better sensitivity and specificity was 1.50 mitoses per mm2. The presence of two or more mitoses/mm2 showed a better relationship with prognostic variables and both the overall and disease-free survival than the presence of 1 or more mitoses/mm2. This happens especially in melanomas thicker than 0.8 mm and it could affect the staging in cases with Breslow between 1 and 2 mm. CONCLUSIONS: A mitotic rate of two or more mitoses per mm2 in cutaneous melanoma should be considered as a more accurate prognostic factor than one or more mitoses per mm2, particularly in tumors equal or greater than 0.8 mm in thickness.

Usefulness of lymphocyte-to-monocyte, neutrophil-to-monocyte and neutrophil-to-lymphocyte ratios as prognostic markers in breast cancer patients treated with neoadjuvant chemotherapy

Background. Nowadays, neoadjuvant chemotherapy (nCT) in breast cancer is more and more standardized, not only in advanced tumours but also in those for which there is an attempt to achieve breast-conserving surgery. In literature, we can find evidences of the relationship between several types of tumours and systemic inflammatory response. Our objective is to analyse the prognostic value of blood parameters (lymphocytes, neutrophils, monocytes, lymphocyte-to-monocyte ratio (LMR), neutrophil-to-monocyte ratio (NMR) and neutrophil-to-lymphocyte ratio (NLR) in breast cancer (BC) patients treated with nCT. Methods. A retrospective cohort of 150 breast cancer patients treated with nCT and subsequently with surgery was analysed. Data about the patients, histology, response to chemotherapy and peripheral blood values of lymphocytes, monocytes and neutrophils was collected, and used to calculate the LMR, NMR and NLR. Univariate and multivariate analyses were performed for the variables to see the relationship of the ratios to disease-free survival (DFS) and overall survival (OS). Results. Patients with high LMR (≥5.46) and low NLR (<3.33) were associated with a lower percentage of relapse (P = 0.048 and P = 0.015, respectively) and, above all, NLR was associated with a better survival (P = 0.024), being those factors that predict a good progress. Conclusion. High LMR and low NLR can be considered as favourable prognostic factors in BC patients treated with nCT (AU)

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Usefulness of lymphocyte-to-monocyte, neutrophil-to-monocyte and neutrophil-to-lymphocyte ratios as prognostic markers in breast cancer patients treated with neoadjuvant chemotherapy.

BACKGROUND: Nowadays, neoadjuvant chemotherapy (nCT) in breast cancer is more and more standardized, not only in advanced tumours but also in those for which there is an attempt to achieve breast-conserving surgery. In literature, we can find evidences of the relationship between several types of tumours and systemic inflammatory response. Our objective is to analyse the prognostic value of blood parameters (lymphocytes, neutrophils, monocytes, lymphocyte-to-monocyte ratio (LMR), neutrophil-to-monocyte ratio (NMR) and neutrophil-to-lymphocyte ratio (NLR) in breast cancer (BC) patients treated with nCT. METHODS: A retrospective cohort of 150 breast cancer patients treated with nCT and subsequently with surgery was analysed. Data about the patients, histology, response to chemotherapy and peripheral blood values of lymphocytes, monocytes and neutrophils was collected, and used to calculate the LMR, NMR and NLR. Univariate and multivariate analyses were performed for the variables to see the relationship of the ratios to disease-free survival (DFS) and overall survival (OS). RESULTS: Patients with high LMR (≥5.46) and low NLR (<3.33) were associated with a lower percentage of relapse (P = 0.048 and P = 0.015, respectively) and, above all, NLR was associated with a better survival (P = 0.024), being those factors that predict a good progress. CONCLUSION: High LMR and low NLR can be considered as favourable prognostic factors in BC patients treated with nCT.

Tumor suppressor SET9 guides the epigenetic plasticity of breast cancer cells and serves as an early-stage biomarker for predicting metastasis.

During the course of cancer progression, neoplastic cells undergo dynamic and reversible transitions between multiple phenotypic states, and this plasticity is enabled by underlying shifts in epigenetic regulation. Our results identified a negative feedback loop in which SET9 controls DNA methyltransferase-1 protein stability, which represses the transcriptional activity of the SET9 promoter in coordination with Snail. The modulation of SET9 expression in breast cancer cells revealed a connection with E2F1 and the silencing of SET9 was sufficient to complete an epigenetic program that favored epithelial-mesenchymal transition and the generation of cancer stem cells, indicating that SET9 plays a role in modulating breast cancer metastasis. SET9 expression levels were significantly higher in samples from patients with pathological complete remission than in samples from patients with disease recurrence, which indicates that SET9 acts as a tumor suppressor in breast cancer and that its expression may serve as a prognostic marker for malignancy.

Targeting the epigenetics of the DNA damage response in breast cancer.

Cancer is as much an epigenetic disease as it is a genetic disease, and epigenetic alterations in cancer often serve as potent surrogates for genetic mutations. Because the epigenetic factors involved in the DNA damage response are regulated by multiple elements, therapies to target specific components of the epigenetic machinery can be inefficient. In contrast, therapies aimed at inhibiting the methionine cycle can indirectly inhibit both DNA and protein methylation, and the wide variety of genes and pathways that are affected by these methylations make this global strategy very attractive. In the present study, we propose an adjuvant therapy that targets the epigenetics of the DNA damage response in breast cancer cells and that results in efficient apoptosis and a reduction in distant metastases in vivo. We observed that a combined therapy designed to uncouple adenosine metabolism using dipyridamole in the presence of a new synthetic antifolate, 3-O-(3,4,5-trimethoxybenzoyl)-(-)-catechin, simultaneously and efficiently blocked both the folic cycle and the methionine cycle in breast cancer cells and sensitized these cells to radiotherapy. The treatment impeded the recruitment of 53BP1 and BRCA1 to the chromatin regions flanking DNA double-strand breaks and thereby avoided the DNA damage responses in breast cancer cells that were exposed to ionizing radiation. In addition, this hypomethylating therapy was also efficient in reducing the self-renewal capability of breast cancer-initiating cells and induced reversion of mesenchymal phenotypes in breast cancer cells.

Superparamagnetic iron oxide as a tracer for sentinel node biopsy in breast cancer: A comparative non-inferiority study.

AIMS: The gold standard for detection of Sentinel Lymph Nodes (SLN) is a combined radioisotope and blue dye breast injection, using a gamma probe (GP). A new, non-radioactive method was developed, using a tracer (Sienna+(®)) of superparamagnetic iron oxide (SPIO) nanoparticles and a manual magnetometer (SentiMag(®)) (SM). The IMAGINE study was designed to show the non-inferiority of SM compared to GP, for the detection of SLN in breast cancer patients with SLN biopsy indication. METHODS: From November 2013 to June 2014, 181 patients were recruited, and 321 nodes were excised and assessed ex-vivo. Readings from both SM and GP devices were recorded during transcutaneous, intraoperative, and ex-vivo detection attempts. RESULTS: At the patient level, ex-vivo detection rates (primary variable) with SM and GP were 97.8% and 98.3% (concordance rate 99.4%). Transcutaneous and intraoperative detection rates were 95.5% vs 97.2%, and 97.2% vs 97.8% for SM and GP respectively (concordance rates > 97%). At the node level, intraoperative and ex-vivo detection rates were 92.5% vs 89.3% and 91.0% vs 86.3% for SM and GP respectively. In all cases the non-inferiority of SM compared to SM was shown by ruling out a predefined non-inferiority margin of 5%. CONCLUSIONS: Our study showed the non-inferiority of SM as compared to GP. Moreover, the ex-vivo and intraoperative detection rates at the node level were slightly higher with SM.

Linfadenectomía axilar completa frente observación en pacientes con micrometástasis en el ganglio centinela por neoplasia de mama. Resultados preliminares del ensayo clínico multicéntrico AATM 048/13/2000 / Complete axillary lymph node dissection versus clinical follow-up in breast cancer patients with sentinel node micrometastases. Interim analysis of the Spanish multicenter clinical trial. AATM 048/13/2000

Objetivo: Conocer la supervivencia, control o recidiva dela enfermedad, y calidad de vida de las pacientes con micrometástasisen el ganglio centinela no sometidas a vaciamientoaxilar.Pacientes y método: Un ensayo clínico prospectivo aleatorizadoen dos brazos, uno con pacientes con micrometástasis enel ganglio centinela que serían sometidas a observación clínica yotro brazo similar pero con linfadenectomía en un segundotiempo quirúrgico. Las pacientes serían seguidas detalladamentedurante cinco años. La muestra constaría de 176 pacientes porbrazo (total 352) para conseguir solidez estadística.Resultados: Hasta el momento se han incluido 120 pacientes(cabe decir que el estudio se mantiene activo). Descontandolos abandonos (7 en el grupo control y 2 en el experimental)permanecen en el estudio 54 en la rama control y 57en la experimental. En el grupo control se encontraron 8 vaciadospositivos (7 de ellos presentaban únicamente un segundoganglio afectado), mientras que en el grupo experimentalapareció una recidiva axilar local (por palpación, siendo el únicoganglio afectado en la linfadenectomía). La paciente se encuentraen la actualidad libre de enfermedad.El estudio no ha terminado. El tiempo máximo de seguimientoes de 47 meses, insuficiente para concluir. Queda sinembargo, abierto, pues consideramos que la pregunta planteadasigue siendo todavía de actualidad

Objective: To asses the impact of SN technique on thewellbeing and performance status of breast cancer patients,specifically targeting the finding of axillary micrometastatic disease.Patients and method: To achieve such objective, a randomizedprospective clinical trial was devised with two arms. Inone arm, patients with SN micrometastases are the subject ofplain clinical follow-up (experimental arm). In the other arm, patientsare submited for second-sugery completion ALND (controlarm). All patients are intended for a five-year follow-up period,and the accrual goal is 176 patients per arm (352 overall).Results: The study is still in the accrual phase. Up untilnow, 120 patients have been entered. There have been 7withdrawals in the control group and 2 in the experimentalgroup. 54 patients are being followed in the control arm, and57 in the study arm. In the control arm, 8 completion ALNDturned out positive, in seven only with one additional (non-sentinel)lymph-node metastasis. In the study arm, one axillary recurrencehas been observed in a single lymph-node, one yearafter primary surgery. Two years after completion ALND, thepatient is free of disease. This is a still ongoing study. A maximum follow-up periodof 47 months is obviously not enough to draw solid conclusions.It will be open for further accrual as the proposed questionis still in need of a definite answer

Enfisema subcutáneo de miembro inferior como primera manifestación de una dehiscencia colónica / Subcutaneous emphysema of the lower limb as presenting manifestation of colon dehiscence

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[Selective sentinel node biopsy in melanoma using preoperative lymphoscintigraphy location and intraoperative detection gamma probe]. / Biopsia selectiva del ganglio centinela en el melanoma mediante localización con linfogammagrafía preoperatoria y sonda de detección gamma intraoperatoria.

BACKGROUND: The experience in detection of sentinel lymph node in melanoma using preoperative scintigraphy and intraoperative gamma probe is referred. PATIENTS AND METHODS: We studied 60 patients with stage I-II melanoma who underwent sentinel lymph node biopsy performed using 99m-Tc-labelled sulphur colloid as radioactive tracer. A preoperative scintigraphy was performed and intraoperative gamma probe was used to localize the sentinel node in all cases. Scintigraphy results, effectiveness of intraoperative detection (technical efficacy), pathological results, and follow-up have been studied. RESULTS: Preoperative detection was 98.3% and the mean basin detected was 1.17. There were multiple basins especially when melanomas were on the trunk. Technical efficacy was 98.4% and intraoperative detection was more difficult in parotid gland region. HMB-45 immunohistochemical staining was essential in pathological studies, in whom 10% were positives. Lymphadenectomy could be avoided in 90% of the patients. Recurrences were not detected during follow-up and metastases were found only in non biopsied cases. Sentinel node biopsy morbidity was significative lesser than that of lymphadenectomy. CONCLUSIONS: Preoperative scintigraphy and intraoperative gamma probe use to localize sentinel node in melanoma have a high efficacy. They can reveal multiple basins and they allow a more selective surgical approach and a minimal dissection.

El desarrollo de seroma poslinfadenectomía axilar por cáncer de mama y su relación con determinados parámetros del drenaje aspirativo / Development of axillary seroma after lymphadenectomy for breast cancer and its relationship with several parameters of suction drainage

Objetivos. La aparición de seromas axilares es la complicación más frecuente tras la linfadenectomía axilar. En este trabajo estudiamos algunos parámetros relacionados con el uso de drenajes quirúrgicos que podrían resultar predictivos del desarrollo de dichos seromas. Pacientes y método. Se han estudiado, de forma prospectiva, 100 pacientes intervenidas de manera consecutiva por cáncer de mama y en las que se realizó linfadenectomía axilar de los tres niveles como parte de su tratamiento. En todas se colocó en la intervención un drenaje axilar, y se registraron datos sobre el débito y duración de dicho drenaje en el postoperatorio. Estos parámetros se compararon según desarrollaran las pacientes seromas que precisasen punciones evacuadoras. Resultados. Sólo se encontraron diferencias significativas en el débito medio de los tres últimos días de drenaje, encontrándose una relación entre el desarrollo de seromas y más de 50 ml del citado débito. No encontramos diferencias en el resto de parámetros, incluyendo la técnica utilizada. Conclusiones. La retirada del drenaje axilar cuando el débito medio de los tres últimos días es menor de 50 ml, es una medida eficaz a la hora de tratar de evitar el desarrollo de seromas axilares postoperatorios tras linfadenectomías por cáncer de mama (AU)

Miositis osificante aguda / Acute myositis ossificans

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Evolution of the need for operation for peptic pyloric stenosis over a period of 24 years (1976-1999).

OBJECTIVE: To analyse the need for operation for pyloric stenosis caused by duodenal ulcer over a period of 24 years (1976-1999). DESIGN: Retrospective study. SETTING: University hospital, Spain. SUBJECTS: 156 patients operated on for peptic pyloric stenosis. MAIN OUTCOME MEASURES: The number of patients operated on yearly were grouped into 4-year periods for statistical comparison. RESULTS: The number of cases operated on each year steadily decreased between 1976 and 1999. In the 1988-1991 period there was a significant reduction (p <0.05), which continued over the next two 4-year periods, particularly the last (p <0.01). CONCLUSION: Although we cannot use this study to establish a direct relation between the decrease in the indication for operations for peptic pyloric stenosis and the use of H2 antagonists, proton pump inhibitors, or treatment to eradicate Helicobacter pylori, we did find a significance difference between the years before and after the introduction of these drugs.

Influencia del tipo de material (látex frente a silicona) y de los corticoides en la producción de fibrosis peritoneal por el tubo de kehr. estudio experimental en ratas / Influence of the type of material employed (latex versus silicone) and of corticosteroids on the production of peritoneal fibrosis due to the presence of a "T"-tube: experimental study in rats

Introducción. La producción de fístulas biliares tras la retirada del tubo de Kehr es un problema de la cirugía de la vía biliar que presenta una importancia aún mayor en el trasplante hepático. En su etiología se han barajado diversos factores, entre los que destacan la interferencia que puedan llegar a ocasionar, en el desarrollo del trayecto fibroso en torno al tubo, tanto el tipo de material utilizado (generalmente látex o silicona) como el tratamiento con corticoides que suele ser administrado a estos pacientes. Objetivos. Comparar el grado de adherencias peritoneales producidas por dos tipos de materiales de tubos en "T" (látex y silicona), y analizar la influencia que sobre aquéllas pueda tener la administración de corticoides. Material y métodos. Se han utilizado 50 ratas hembra distribuidas en cinco grupos (control, látex, silicona, látex más corticoides y silicona más corticoides) y se ha estudiado, mediante un sistema de puntuación, el grado de adherencias peritoneales producidas por un fragmento de tubo de Kehr colocado en el espacio subhepático de la cavidad peritoneal. Se calculó un índice de producción de adherencias, que se utilizó para comparar a los grupos entre sí. Resultados. El índice de producción de adherencias media ñ desviación estándar fue: grupo de látex: 6,7 ñ 1,4; grupo de silicona: 2,1 ñ 1,7; grupos de látex tratados con corticoides: 3,5 ñ 1,4, y grupo de silicona más corticoides: 1,2 ñ 1,3. Se encontraron diferencias al comparar los dos materiales (p < 0,001). La administración de corticoides redujo la producción de adherencias tanto en el grupo de látex (p < 0,001) como en el de silicona (p < 0,05). Conclusiones. Los tubos de silicona condicionan una menor formación de adherencias peritoneales postoperatorias que los de látex, y la administración de corticoides reduce dicha formación en ambos casos (AU)