Implementing Standard Diagnosis and Treatment for Locally Advanced Breast Cancer Through Global Research in Latin America: Results From a Multicountry Pragmatic Trial.

PURPOSE: Breast cancer mortality rates in Latin America (LA) are higher than those in the United States, possibly because of advanced disease presentation, health care disparities, or unfavorable molecular subtypes. The Latin American Cancer Research Network was established to address these challenges and to promote collaborative clinical research. The Molecular Profiling of Breast Cancer Study (MPBCS) aimed to evaluate the clinical characteristics and treatment outcomes of LA participants with locally advanced breast cancer (LABC). PATIENTS AND METHODS: The MPBCS enrolled 1,449 participants from Argentina, Brazil, Chile, Mexico, and Uruguay. Through harmonized procedures and quality assurance measures, this study evaluated clinicopathologic characteristics, neoadjuvant chemotherapy response, and survival outcomes according to residual cancer burden (RCB) and the type of surgery. RESULTS: Overall, 711 and 480 participants in the primary surgery and neoadjuvant arms, respectively, completed the 5-year follow-up period. Overall survival was independently associated with RCB (worse survival for RCBIII-adjusted hazard ratio, 8.19, P < .001, and RCBII [adjusted hazard ratio, 3.69, P < .008] compared with RCB0 [pathologic complete response or pCR]) and type of surgery (worse survival in mastectomy than in breast-conserving surgery [BCS], adjusted hazard ratio, 2.97, P = .001). The hormone receptor-negative-human epidermal growth factor receptor 2-positive group had the highest proportion of pCR (48.9%). The analysis of the ASCO Quality Oncology Practice Initiative breast module revealed high compliance with pathologic standards but lower adherence to treatment administration standards. Notably, compliance with trastuzumab administration varied widely among countries (33.3%-88.7%). CONCLUSION: In LABC, we demonstrated the survival benefit of BCS and the prognostic effect of the response to available neoadjuvant treatments despite an important variability in access to key treatments. The MPBCS represents a significant step forward in understanding the real-world implementation of oncologic procedures in LA.

The -174G>C and -596G>A Polymorphisms Are Not Associated with Circulating IL-6 Levels in Breast Cancer Patients from Jalisco, México.

Introduction: Interleukin-6 (IL-6) is a circulating proinflammatory cytokine that fulfills an important role in the survival and proliferation of cancer cells. Overexpression of IL-6, possibly due to the -174G>C and -596G>A polymorphisms in the IL6 gene, has been shown to be related to breast cancer (BC) and a more aggressive course of the disease. Aim: To determine the influence of the -174G>C and -596G>A polymorphisms of the IL6 gene on the circulating levels of IL-6 in BC patients from Jalisco, México. Methodology: Genotyping of the two polymorphisms was carried out on 208 BC patients and 219 healthy controls through polymerase chain reaction-restriction fragment length polymorphism analyses. In addition, the plasma IL-6 concentration levels were measured in the BC patients. Results: There was no significant association between BC and the IL-6 alleles and genotypes (-174G>C, p = 0.276; -596G>A, p = 0.762) under study. Similarly, there were no significant differences in the mean plasma IL-6 concentrations associated with the polymorphisms that were analyzed (-174G>C, p = 0.839; -596G>A, p = 0.848). Conclusions: No evidence was found that the analyzed polymorphisms are associated with the IL-6 expression or concentration in patients suffering from BC from Jalisco, Mexico.

Porcentaje de adiposidad y su relación con el índice de inmunorreactividad de los receptores hormonales en mujeres mexicanas con cáncer de mama / Adiposity percentage relationship with hormone receptors immunoreactive score in breast cancer Mexican women

INTRODUCTION: Adipose tissue is an important estrogen resource and they are involved in breast cancer development. OBJECTIVE: To establish the relationship between adiposity percentage and the estrogen and progesterone receptors immunoreactive score in Mexican women with breast cancer. METHODS: This is a transversal and analytical study. We identified breast cancer women with cancer histologic diagnosis. We calculated: adiposity percentage and immunoreactive score. We performed correlation analysis between adiposity percentage, body mass index, diabetes mellitus and arterial hypertension, with estrogen and progesterone receptors in breast cancer samples. We perform logistic regression and Odds Ratio estimations. RESULTS: We studied 43 patients with breast cancer and we observed association between adiposity percentage and estrogen and progesterone immnunoreactive score (rP 0.470; p 0.003 and rP 0.328; p 0.042, respectively). The most important risk factor in breast cancer positive to estrogen receptors was obesity (OR 19.1, IC95% 2.1 a 169.1, p 0.008), and previous obesity in breast cancer positive to progesterone receptors (OR 20.7, IC95% 2.3 a 185.9, p 0.007). DISCUSSION: Adiposity percentage is an important risk factor to develop breast cancer positive to hormone receptors related with the risk of breast cancer positive to hormonal receptors (AU)

Introducción: El tejido adiposo es una importante fuente de estrógenos, los cuales se encuentran implicados en el desarrollo de cáncer de mama. Objetivo: Establecer la relación entre el porcentaje de adiposidad y el índice de inmunorreactividad de los receptores a estrógenos y a progesterona en mujeres mexicanas con cáncer de mama. Métodos: Estudio transversal analítico en pacientes con cáncer de mama confirmado con estudio histopatológico. Se estimó el % de adiposidad, y el índice de inmunorreactividad. Se realizó el análisis de correlación entre el porcentaje de adiposidad, el IMC, la presencia de DM2 e hipertensión arterial con la expresión de receptores a estrógeno y progesterona y regresión logística con cálculo de Odds Ratio. Resultados: Se estudiaron 43 pacientes con cáncer de mama y se observó asociación entre el porcentaje de adiposidad y el índice de inmunoreactividad para los RE y RP (rP 0,470; p 0,003 y rP 0,328; p 0,042 respectivamente). El factor de riesgo más importante en cáncer positivo a receptores estrogénicos fue la obesidad (OR 19,1, IC 95% 2,1 a 169,1, p 0,008) y obesidad previa en cáncer positivo a receptores a progesterona (OR 20,7, IC 95% 2,3 a 185,9, p 0,007). Conclusión: El porcentaje de adiposidad es un factor de riesgo importante para desarrollar cáncer de mama positivo a receptores hormonales (AU)

[Adiposity percentage relationship with hormone receptors immunoreactive score in breast cancer mexican women]. / Porcentaje de adiposidad y su relación con el índice de inmunorreactividad de los receptores hormonales en mujeres mexicanas con cáncer de mama.

INTRODUCTION: Adipose tissue is an important estrogen resource and they are involved in breast cancer development. OBJECTIVE: To establish the relationship between adiposity percentage and the estrogen and progesterone receptors immunoreactive score in Mexican women with breast cancer. METHODS: This is a transversal and analytical study. We identified breast cancer women with cancer histologic diagnosis. We calculated: adiposity percentage and immunoreactive score. We performed correlation analysis between adiposity percentage, body mass index, diabetes mellitus and arterial hypertension, with estrogen and progesterone receptors in breast cancer samples. We perform logistic regression and Odds Ratio estimations. RESULTS: We studied 43 patients with breast cancer and we observed association between adiposity percentage and estrogen and progesterone immnunoreactive score (rP 0.470; p 0.003 and rP 0.328; p 0.042, respectively). The most important risk factor in breast cancer positive to estrogen receptors was obesity (OR 19.1, IC95% 2.1 a 169.1, p 0.008), and previous obesity in breast cancer positive to progesterone receptors (OR 20.7, IC95% 2.3 a 185.9, p 0.007). DISCUSSION: Adiposity percentage is an important risk factor to develop breast cancer positive to hormone receptors related with the risk of breast cancer positive to hormonal receptors.

Introducción: El tejido adiposo es una importante fuente de estrógenos, los cuales se encuentran implicados en el desarrollo de cáncer de mama. Objetivo: Establecer la relación entre el porcentaje de adiposidad y el índice de inmunorreactividad de los receptores a estrógenos y a progesterona en mujeres mexicanas con cáncer de mama. Métodos: Estudio transversal analítico en pacientes con cáncer de mama confirmado con estudio histopatológico. Se estimó el % de adiposidad, y el índice de inmunorreactividad. Se realizó el análisis de correlación entre el porcentaje de adiposidad, el IMC, la presencia de DM2 e hipertensión arterial con la expresión de receptores a estrógeno y progesterona y regresión logística con cálculo de Odds Ratio. Resultados: Se estudiaron 43 pacientes con cáncer de mama y se observó asociación entre el porcentaje de adiposidad y el índice de inmunoreactividad para los RE y RP (rP 0,470; p 0,003 y rP 0,328; p 0,042 respectivamente). El factor de riesgo más importante en cáncer positivo a receptores estrogénicos fue la obesidad (OR 19,1, IC 95% 2,1 a 169,1, p 0,008) y obesidad previa en cáncer positivo a receptores a progesterona (OR 20,7, IC 95% 2,3 a 185,9, p 0,007). Conclusión: El porcentaje de adiposidad es un factor de riesgo importante para desarrollar cáncer de mama positivo a receptores hormonales.

TRESK potassium channel in human T lymphoblasts.

TRESK (TWIK-related spinal cord K(+)) channel, encoded by KCNK18 gene, belongs to the double-pore domain K(+) channel family and in normal conditions is expressed predominantly in the central nervous system. In our previous patch-clamp study on Jurkat T lymphoblasts we have characterized highly selective K(+) channel with pharmacological profile identical to TRESK. In the present work, the presence of KCNK18 mRNA was confirmed in T lymphoblastic cell lines (Jurkat, JCaM, H9) but not in resting peripheral blood lymphocytes of healthy donors. Positive immunostaining for TRESK was demonstrated in lymphoblastic cell lines, in germinal centers of non-tumoral lymph nodes, and in clinical samples of T acute lymphoblastic leukemias/lymphomas. Besides detection in the plasma membrane, intracellular TRESK localization was also revealed. Possible involvement of TRESK channel in lymphocyte proliferation and tumorigenesis is discussed.

Plasma cell myeloma associated with Epstein-Barr virus infection in an 11-year-old girl.

Multiple myeloma is extremely rare in children and represents fewer than 1% of all patients with myeloma. We report a case of multiple myeloma in an 11-year-old girl, who presented with a well-differentiated immunoglobulin A/kappa plasmacytoma at the base of the skull at 9 years of age; at that time, the bone marrow biopsy was negative. Two years later, the patient experienced generalized bone pain with multiple lytic bone lesions that affected the skull, long bones, ribs, and clavicle. The bone marrow biopsy showed a well-differentiated (Marschalko-type) multiple myeloma that was positive for CD138 and immunoglobulin A, with kappa light chain restriction. Interestingly, the Epstein-Barr virus (EBV) was detected by in situ hybridization for EBV-encoded RNA (EBER) in the majority of the neoplastic cells from both biopsy specimens. The patient responded favorably to treatment with dexamethasone, thalidomide, and zoledronic acid and is scheduled for bone marrow transplantation.

[Chain of errors in laparoscopic appendectomy]. / Cadena de errores en apendicectomía laparoscópica.

BACKGROUND: The urachal cyst is a rare pathology in the adult patient and in general is asymptomatic. The goal of this presentation is to learn of the errors. CLINICAL CASE: A 22 year old female with clinical diagnosis of acute appendicitis was taken to surgical management. Laparoscopy confirmed the diagnosis. Laparoscopic appendectomy was performed uneventfully. Four weeks in the postoperative period the patient developed reddening and softening in the left surgical wound which was a trocar incision. The initial diagnosis was a granuloma which was removed surgically twice. A fistulogram and abdominal CT scan were negative. Finally, we decided to perform a laparatomy trought the same incision and we found an infected urachal cyst, which was excised. A retrospective analysis of the laparoscopic appendectomy shows the urachal cyst and the perforation by the trocars. CONCLUSION: an inadequate process in the laparoscopic vision, in the diagnosis and technical errors were the cause of this chain of errors and a major temporal damage to this patient. An optimal laparoscopy would have detected the urachal cyst and treated of the two pathologies simultaneously. An adequate trocar placement would not have perforated the urachal cyst and therefore there would have been no postoperative symptoms. Finally open appendectomy could have avoided this chain of errors.

[A clinical and therapeutic analysis in acute megakaryoblastic leukemia]. / Análisis clínico-terapéutico de leucemia aguda megacarioblástica.

OBJECTIVE: to show clinical and therapeutic findings in patients with diagnosis of acute megakaryoblastic leukemia (AML). METHODS: twenty four patients with diagnosis AML was carried out. Clinical, laboratory survey results and treatment response were studied. Nineteen patients had primary form and five secondary, attended during a period of eight years. The diagnosis was established by a highly clinical suspicious, with immunophenotype cytometry flow or/and bone biopsy with immunohistochemistry study which proves definitely AML. RESULTS: Fourteen were women, the median age was 43 years, 18 were treated with antineoplasic agents, ten obtained response, six complete and four partial. The response may improve with schemes with high dose of cytosine arabinoside. CONCLUSIONS: our results with the treatment showed that 27 % patients are alive under maintenance treatment long 18 months. The allogeneic bone marrow transplant seems to be one more option in long term.

Deflazacort induced stronger immunosuppression than expected.

Prednisone (PDN) impairs cognitive functioning and brain structures in humans and animals. Deflazacort (DFZ) is a synthetic glucocorticoid claimed to have lesser side effects than prednisone. The objective of this study was to assess whether chronic administration (90 days) of DFZ produces less neuronal degeneration and glial reactivity than PDN. Male Swiss-Wistar rats were studied. Controls received 0.1 ml distilled water orally. The PDN group received prednisone 5 mg per kg per day orally, and the DFZ group received deflazacort 6 mg per kg per day orally. This model had to be assembled in three different occasions due to excess mortality in the DFZ group. A fourth model was assembled using only the DFZ group and slides of water and PDN-exposed rats from a previous study were used as comparators. The index of degenerated neurons and the number and cytoplasmic transformation of astrocytes and microglia cells were evaluated in the prefrontal cortex, CA1, and CA3 hippocampus. The results show that the overall mortality was 49% in the DFZ group, 4.5% in the PDN group, and none of the controls died. Routine necropsy showed infection in multiple organs. The PDN group had two times higher neuronal degeneration in the prefrontal cortex, almost 11 times in CA1, and four times in CA3 hippocampus when compared with controls and DFZ group. Astrocytes reactivity was increased in the PDN- and DFZ-exposed rats compared with controls. The DFZ group showed an average of four times less microgial cells in the three studied regions when compared with controls and the PDN group. In conclusion, it seems that DFZ at the equivalent licensed dose produced a stronger immunosuppressive effect--systemic and in brain tissue--than PDN, but induced less neuronal damage. The immunosuppressant magnitude of DFZ should be further studied in clinical settings.

[Efficacy of two Helicobacter pylori eradication treatments in children with recurrent abdominal pain]. / Eficacia de dos esquemas de erradicación de Helicobacter pylori en niños con dolor abdominal recurrente.

OBJECTIVE: To compare clinical and bacteriologic efficacy of two therapeutic trials to eradicate Helicobacter pylori (H. pylori) in two series of pediatric patients with recurrent abdominal pain (RAP). MATERIALS AND METHODS: n = 36 children with RAP-associated H. pylori infection. Age 9.8 +/- 3.1 years, 19 boys and 17 girls. Clinical and bacteriologic efficacy of two therapeutic trials was compared: Group A (1996-1997), n = 9, amoxicillin, bismuth subsalicilate, and metronidazol, and group B (1991-1993), n = 27, omeprazol, amoxicillin, and clarithromycin. Initially and post-treatment, H. pylori evaluation was carried out with upper endoscopy and gastric biopsies. For statistics, we used Student t test, chi2, Fisher test, and Kruskal-Wallis analysis of variance (alpha = 0.05). RESULTS: We found that 33/36 cases had gastritis at endoscopy, two with duodenal ulcer; nodular gastritis was observed in more than one half of total cases. All cases fulfilled histologic criteria of gastritis according to Sydney Score. In group A eradication was achieved in 28.6%, while in group B eradication rose to 77.8% (p < 0.05). In group A, 8/9 and in group B 15/27 persisted with RAP (p = 0.113). CONCLUSIONS: High frequency of abnormal and histologic findings was observed in the series presented on children with RAP and H. pylori. Eradication efficacy in the omeprazol/amoxicillin/clarithromycin group was higher when compared with bismuth subsalicilate/amoxicillin/metronidazol trial. This efficacy is comparable to pediatric series treated with the same therapeutic trial.

Hemorragia masiva del aparato digestivo, secundaria a Malacoplaquia colónica ulcerada / Massive hemorrhage of the digestive tract secondary to ulcerated colonic malacoplakia

Reportamos un caso de malacoplaquia del colon que se presentó como hemorragia del tubo digestivo bajo masiva en una paciente femenina de 55 años de edad. Un colon por enema demostró lesiones polipoideas. La colonoscopía reveló nodulaciones pseudo-polipoideas color blanco amarillento, aparentando pequeñas pústulas que se extendían a todo el colon a partir de 2 cm del margen anal. La laparotomía reveló la presencia de masas lobuladas en la luz intestinal y lesiones amarillentas en forma de placas transmulares que infiltraban pared duodenal, así como gran cantidad de ganglios en todo el mesenterio. Realizamos protocolectomía. El estudio microscópico demostró infiltración masiva de histiocitos y numerosos cuerpos de Michaelis-Gutmann. Esta enfermedad se presenta casi exclusivamente en las vías urinarias y es extremadamente rara en el intestino. Enfatizamos en la importancia de un adecuado examen histológico que nos permita un diagnóstico correcto