Presentation of Wernicke encephalopathy in patient secondary to one anastomosis gastric bypass. Case report and literature review.

Wernicke encephalopathy, which is caused by a thiamine deficiency, occurs in 0.8-2% of the population. Only 16% present the typical triad of this disease: nystagmus, confusion and ataxia. We present the case of a postoperative patient with a one anastomosis gastric bypass with reoperation undergoing a Roux-en-Y gastric bypass that begins with confusion and nystagmus on her third postoperative day. The diagnosis of Wernicke encephalopathy is made by imaging, and vitamin B1 is administered with total improvement of nystagmus and altered state of consciousness (lethargy, bradypsychia, bradylalia).

La encefalopatía de Wernicke se produce por una deficiencia de tiamina se presenta en un 0.8-2% de la población. Solo el 16% de los casos presentan la tríada típica de esta enfermedad: nistagmo, confusión y ataxia. Presentamos el caso de una paciente operada de bypass gástrico de una anastomosis con reintervención convirtiendo a bypass gástrico en Y de Roux que en su tercer día de posoperatorio comienza con confusión y nistagmo. Se realiza por imagen el diagnóstico de encefalopatía de Wernicke se administra vitamina B1 con mejoría total del nistagmo y alteración del estado de consciencia (letargia, bradipsiquia, bradilalia).

Case report: Buschke-Lowenstein tumor, a giant anal condyloma acuminata.

24-year-old man with positive HIV, with a giant exofitic anal condyloma, with a clinical presentation of a painfull suppurative anal condyloma with a pathology report of an in situ squamous cell carcinoma. The purpose of the investigation is a case report and the procedure was observational. The finding was a Buschke-Lowenstein tumor.

Varón de 24 años, con infección por el virus de la inmunodeficiencia humana, que presenta una tumoración exofítica, dolorosa y supurativa, con reporte positivo de virus de papiloma humano y reporte histopatológico de carcinoma espinocelular sin evidencia de diseminación (in situ). El propósito de la investigación es un reporte de caso y el procedimientos fue observacional. El hallazgo fue un tumor de Buschke-Lowenstein.

An Unexpected Cause of Abdominal Discomfort: Non-pancreatic Mesenteric Pseudocyst.

Mesenteric cysts (MCs), rare entities of embryologic origin, predominantly affect the small bowel's mesentery. The clinical manifestations of MCs often lack specificity, which complicates diagnosis. Given their rarity, detailed reporting of MC cases is essential to enhance understanding and improve treatment strategies. We present a case of a 45-year-old male who presented to the emergency department with a one-month history of abdominal pain in the umbilical region, postprandial fullness, progressive decrease in food intake, 12 kg weight loss, and increased abdominal girth. Computed tomography (CT) imaging revealed a well-defined mass in the jejunoileal area. During the exploratory laparotomy, we identified and excised a fibrotic mass on the mesentery of the ileal jejunum, which was not adherent to the intestines. We discharged the patient with no complications following an uneventful four-day observational period. Histopathological examination, including immunohistochemical staining, confirmed the lesion as a non-pancreatic mesenteric pseudocyst. On the follow-up visit, the patient reported no complications. This case report underscores the solitary, multilocular nature of the jejunoileal MC, distinct for its serosanguineous fluid content. In conclusion, this case highlights the diagnostic challenge of MCs and illustrates the potential for successful management with a timely and multidisciplinary approach.

Small Cell Neuroendocrine Carcinoma of the Lung Discovered by Acute Appendicitis Metastasis: An Experience at Our Hospital.

Acute appendicitis is the most common cause of abdominal pain that requires surgery. Appendiceal cancer is rare, comprising nearly 4% of all gastrointestinal diagnoses. It is common to find neuroendocrine neoplasms due to metastasis in this site. Appendix tumors are usually asymptomatic; however, if they are advanced or have metastases, they can cause abdominal symptoms. Computed tomography (CT) is commonly used to diagnose acute appendicitis in these cases. CT usually shows an increased appendiceal diameter with thickening (>3 mm) of the appendiceal wall, an intraluminal fluid depth >2.6 mm, and periappendiceal inflammation. Histopathological findings confirm the diagnosis. Medical and surgical management depends on physical characteristics such as size, location, and degree of evolution. We present the case of a 77-year-old woman with a family history of well-controlled type 2 diabetes mellitus and hypertension. She was referred to our institution after four days of abdominal pain in the epigastrium and both flanks accompanied by fever. An abdominal CT showed left pleural effusion and appendicular thickening. Laboratory tests showed high blood glucose levels, leukocytosis at the expense of neutrophils, an increased platelet count, and decreased albumin and total proteins. The CT scan also showed a calcified granuloma in the anterior segment of the right upper lobe and an irregular image with partially defined hypodense borders in the liver in segment IVb. We report our experience with the diagnosis, management, and treatment decisions of this case. It is important to mention that the first diagnosis was acute appendicitis. This diagnosis motivated us to seek other symptoms and signs by direct questioning and imaging studies leading us to diagnose metastatic lung cancer.

Fecopneumothorax secondary to a late traumatic diaphragmatic injury

Traumatic diaphragmatic hernias were first described by Ambroise Paré in 1579, who reported the case of an artillery captain, that presented an intestinal perforation that had caused a diaphragmatic hernia (Bhatti and Dawani, 2015). The timely diagnosis of a traumatic diaphragmatic hernia can be a challenge, which requires extensive knowledge of the kinematics of trauma, as well as clinical and radiological evidence (Petrone et al., 2017). We present the case of a 60-year-old male who presented blunt abdominal trauma due to a traffic accident, causing an undetected diaphragmatic hernia in his initial evaluation; months after de incident goes to the emergency room (ER) with hemodynamic instability and septic shock. A diagnosis of complicated diaphragmatic hernia and fecopneumothorax is made, for which he undergoes surgery.

Spontaneous splenic rupture, an unusual presentation of tuberculosis.

INTRODUCTION: Spontaneous splenic rupture from tuberculosis (TB) is a very unusual presentation within the wide range of presentations of this infectious disease. CLINICAL CASE: A 40-year-old male with a diagnosis of human immunodeficiency virus, begins with fever and pain in the left hypochondrium. A computed tomography scan was performed, showing probable splenic abscesses; suddenly, it begins with hemodynamic deterioration, exacerbation of pain, a surgical exploration was performed, showing spontaneous splenic rupture. Microscopic study of the spleen shows the presence of Mycobacterium tuberculosis. CONCLUSIONS: This is yet another presentation of TB, which can become a surgical emergency.

INTRODUCCIÓN: La ruptura esplénica espontánea por tuberculosis es una presentación muy inusual dentro de la amplia gama de presentaciones de esta enfermedad infectocontagiosa. CASO CLÍNICO: Masculino de 40 años con diagnóstico de VIH, inicia con fiebre y dolor en hipocondrio izquierdo. Se realiza TAC evidenciando probables abscesos esplénicos; súbitamente comienza con deterioro hemodinámico, agudización del dolor, se realiza exploración quirúrgica evidenciando ruptura esplénica espontánea. Al estudio microscópico del bazo se observa presencia de Mycobacterium Tuberculosis. CONCLUSIONES: Esta es una presentación más de la TB, la cual puede convertirse en una urgencia quirúrgica.

Traumatic rupture of diaphragm with splenic herniation. An unusual cause of hemothorax.

The traumatic diaphragmatic hernia is considered a rare clinic condition and represents a diagnostic challenge. Its presentation is mainly a surgical emergency, leading to scarce time for complementary image studies. We present a case of a 21-year-old male who suffered a penetrating wound in the left hemitorax from whom is suspected to have a traumatic visceral herniation into the thoracic cavity by chest X-ray, confirming a splenic herniation with intrathoracic hemorrhage, as well as the proposal of a management algorithm for this defiant cases.

La hernia diafragmática traumática es poco frecuente en la clínica y representa un reto diagnóstico, ya que su aparición es principalmente de emergencia y esto propicia poco tiempo para la realización de estudios de imagen complementarios. Presentamos el caso de un varón de 21 años que sufrió una herida penetrante en el hemitórax izquierdo con sospecha de herniación traumática diafragmática de vísceras abdominales al tórax por radiografía, y en el quirófano se confirmó una herniación esplénica con hemorragia intratorácica. Se propone un algoritmo de manejo en estos casos tan desafiantes.

Complications and treatment to liver wound by gunshot. A retrospective approach.

INTRODUCCIÓN: Un trauma penetrante puede dañar una variedad de órganos. Dado que el hígado es un órgano sólido inelástico, no tiene la tolerancia al estiramiento necesaria para hacer frente a una herida por proyectil de arma de fuego (GSW). MÉTODOS: Este fue un estudio retrospectivo, observacional y descriptivo de 53 registros clínicos de pacientes ingresados en el Departamento de Cirugía por trauma hepático (LT) por un GSW. RESULTADOS: Del total de historias clínicas analizadas, el 89% de los pacientes presentaron una lesión asociada con LT. La lesión orgánica asociada más frecuente fue la torácica, específicamente la lesión pulmonar, en el 58%. El predictor más importante de mortalidad fue una estancia en la unidad de cuidados intensivos (UCI), que aumentó el riesgo unas 21 veces. CONCLUSIÓN: Una estadía en la UCI, seguida de la presencia de fracturas, fue el predictor más importante de mortalidad. Se necesitan nuevas medidas de pronóstico para contrarrestar las variables que ha creado el aumento de GSW, además de disminuir el tiempo de espera desde el evento traumático hasta el tratamiento relevante. INTRODUCTION: A penetrating trauma can damage a variety of organs. Since the liver is an inelastic solid organ, it does not have the necessary stretch tolerance to cope with a gunshot wound (GSW). METHODS: This was a retrospective, observational, and descriptive study of 53 clinical records of patients admitted to the Department of Surgery for liver trauma (LT) by a GSW. RESULTS: Of the total clinical records analyzed, 89% of the patients presented a lesion associated with LT. The most common associated organic lesion was thoracic, specifically lung injury, in 58%. The most important predictor of mortality was a stay in the intensive care unit (ICU), which increased the risk about 21 times. CONCLUSION: A stay in the ICU, followed by the presence of fractures, was the most important predictor of mortality. New prognostic measures are needed to counteract the variables that the increase in GSWs has created, in addition to decreasing the waiting time from the traumatic event to relevant treatment.

Pseudoaneurisma de la arteria femoral profunda secundario a trauma penetrante: reporte de caso / Deep femoral artery pseudoaneurysm secondary to penetrating trauma: case report

Resumen Objetivo: El objetivo del trabajo es presentar una opción terapéutica adecuada para los pseudoaneurismas de la femoral profunda secundarios a trauma penetrante, así como realizar una revisión de la literatura sobre el manejo en estas patologías. Caso clínico: Paciente masculino de 21 años quien 5 meses previos a su valoración sufre una herida por arma punzocortante en el muslo izquierdo, desarrollando aumento de volumen el sitio de la lesión, dolor y limitación al movimiento. Se diagnostica un pseudoaneurisma de la arteria femoral profunda de 2,3 cm x 2,1 cm x 2,7 cm y un hematoma adyacente de 13,5 cm x 12,6 cm x 23 cm. Se realiza exclusión del pseudoaneurisma mediante cirugía endovascular con coils, posteriormente se evacúa el hematoma adyacente. Resultados: El paciente egresa al tercer día posoperatorio con mejoría de la sintomatología, antibioticoterapia y analgesia. Discusión y Conclusión: En el caso presentado la exclusión del pseudoaneurisma mediante coils facilitó el control de éste y la evacuación del hematoma adyacente, disminuyendo el riesgo de sangrado. Por lo que consideramos adecuada esta conducta terapéutica en pseudoaneurismas de la femoral profunda.

Aim: The aim of this paper is to present a case of a deep femoral artery pseudoaneurysm secondary to a penetrating trauma in the left thigh, its management and a literature review. Clinical Case: 21-year-old male referred to the emergency department of our institution 5 months after he was injured with a knife on his left thigh, with severe local swelling, local pain, and difficulty to the mobilization of the left leg. A 2.3 cm x 2.1 cm x 2.7 cm deep femoral artery pseudoaneurysm was diagnosed with a 13.5 cm x 12.6 cm x 23 cm adjacent hematoma. Endovascular exclusion was made with coils and evacuation of the hematoma with open surgery. Results: The patient was discharged on the third day postop without pain and walking with antibiotics and follow-up to a month did not reveal any complications. Discusion and Conclusion: Exclusion with coils is an adequate management in deep femoral pseudoaneurysms that facilitates the evacuation of the hematoma lowering the risk of bleeding.

Pectus up: la nueva técnica de tracción para pectus excavatum. Primera cirugía en el noreste de México.

El pectus excavatum es la deformidad de la caja torácica frecuente, siendo el sexo masculino el mayormente afectado. Presentamos el caso de un varón de 16 años con pectus excavatum e índice de Haller de 4, a quien se somete a cirugía de pectus up con sistema de tracción esternal externa y fijación con tornillos. Se obtuvo una muy buena respuesta funcional y estética en su posoperatorio. La cirugía de pectus up como método poco invasivo da buenos resultados posoperatorios.The pectus excavatum is the most frequent deformity of the rib cage, with the male sex being the most affected. We present the case of a 16-year-old male with the presence of pectus excavatum with a Haller's index of 4 who undergoes pectus up surgery with an external sternal traction system and screw fixation. A very good functional and aesthetic response was obtained. The pectus up surgery as a less invasive technique has good postoperative results.

Quiste de duplicación gástrica: inusual presentación en adultos, tratado con éxito por laparoscopía.

Las duplicaciones gastrointestinales son malformaciones congénitas raras que pueden presentarse en diferentes partes del tracto gastrointestinal, de tamaño y sintomatología variable. Las duplicaciones gástricas representan el 3-5% de estas malformaciones. La presentación más frecuente es la quística, en la mayoría de los casos en la curvatura mayor. El diagnóstico es raro en la edad adulta y el tratamiento de elección es quirúrgico, el cual puede llevarse a cabo de forma convencional o por mínima invasión. Se presenta el caso de una mujer adulta con diagnóstico de quiste de duplicación gástrica en fondo gástrico adyacente a la unión gastroesofágica a quien se realizó resección total por laparoscopia.Gastrointestinal duplications are rare congenital malformations, they can appear in different parts of the gastrointestinal tract, of variable size and symptomatology. Gastric duplications represent 3-5% of these malformations, the most frequent presentation is statistical, located mostly in the greater curvature, the diagnosis is rare in adulthood, the treatment of choice is surgical, which can be carried out in a conventional or minimally invasive manner. We present the case of an adult woman diagnosed with a gastric duplication cyst in the gastric fundus adjacent to the gastroesophageal junction, who underwent total resection by laparoscopy.

Estudios de laboratorio como herramienta en la identificación de apendicitis aguda y su diferenciación con hiperplasia linfoide / Laboratory studies as a tool for the differential diagnosis between acute appendicitis and lymphoid hyperplasia

RESUMEN Antecedentes: La apendicitis aguda (AA) es una de las principales patologías quirúrgicas en México y el mundo. A pesar de ser una patología frecuente, el manejo quirúrgico presenta una tasa del 10-20% de apendicitis blancas (AB) o hiperplasia folicular linfoide (HPL) por histopatología. Objetivo: Comparar los hallazgos clínicos, de laboratorio y radiológicos de pacientes con sospecha de AA con su diagnóstico por histopatología. Material y métodos: El estudio es retrospectivo, observacional y transversal. Se analizaron los datos de los pacientes con diagnóstico clínico de apendicitis aguda, desde febrero de 2013 hasta diciembre de 2017, atendidos en un hospital de tercer nivel en Monterrey, México. Se compararon los hallazgos de los pacientes con diagnóstico de AA vs. HPL, AA no complicadas vs. AA complicadas y pacientes pediátricos vs. adultos. Se realizó un análisis descriptivo por medio de frecuencias y porcentajes, y mediana y rango intercuartil (RIC), dada la distribución no paramétrica de estas variables. Se compararon los hallazgos por laboratorio mediante la prueba de Mann-Whitney. Se consideró una p< 0,05 como estadísticamente significativa. Resultados: En nuestro medio, ambos sexos tienen la misma frecuencia de presentación de AA. El tiempo de evolución es significativo en la presentación frecuente de AA complicada. Existe asociación entre leucocitosis, neutrofilia total y porcentual y recuento plaquetario mayor en presencia de AA vs. HPL. Conclusión: Los estudios de laboratorio no muestran cambios significativos en pacientes pediátricos con AA. En adultos con AA no complicada vs. apendicitis complicada, el aumento en WBC, NEU y NEU% son estadísticamente significativos.

ABSTRACT Background: Acute appendicitis (AA) is one of the main surgical pathologies in our country and worldwide. Despite being a surgery that is frequently done, it is still reported a 10-20% of negative appendectomies (NA). Objective: The objective of the study is to compare clinical, laboratory and radiology results with the histopathology diagnosis. Material and methods: A retrospective study was done analyzing the data of patients with clinical diagnosis of AA from February 2013 to December 2017, in a tertiary hospital in Monterrey, Mexico. They were classified by their histopathological results into different groups: AA or NA; and the AA was subdivided into complicated AA and uncomplicated AA. Finally, these groups were also subdivided by ages, into pediatric and adult groups of each category. A descriptive analysis was made using frequencies, percentages, median and the interquartile range. Laboratory results were compared with the Mann-Whitney test. Considering a p-value of p < 0.05 as statistically significant. Results: In our group of patients both genders had AA in a similar frequency, the time between the appearance of symptoms and reaching for medical advice was an important factor for having complicated AA. There is a correlation between leukocytosis, neutrophil count and platelet count elevated in presence of AA against NA. Conclusion: Laboratory studies did not report significant changes in pediatric patients with AA. In adults with uncomplicated AA vs. complicated AA, white blood cell count, and neutrophil count are statistically significant.

Hernia diafragmática congénita recurrente asociada a malrotación intestinal / Recurrent congenital diaphragmatic hernia associated with intestinal malrotation

RESUMEN La recurrencia de las hernias diafragmáticas congénitas, luego de reparadas quirúrgicamente, es de baja frecuencia. Se presenta el caso de un paciente masculino de 22 años con hernia diafragmática congénita reparada inicialmente al segundo día de vida, el cual presenta disnea grado 1 y enfermedad por reflujo gastroesofágico. Se evidencia por medio de imagen una hernia diafragmática izquierda, el saco herniario con contenido de bazo, colon, cola de páncreas y glándula suprarrenal izquierda. Se aborda de manera abdominal mediante incisión subcostal izquierda, se reduce el saco herniario, se coloca malla tipo en el defecto diafragmático y se realiza procedimiento de Ladd por la presencia de malrotación intestinal.

ABSTRACT Recurrence of congenital diaphragmatic hernia, after surgical repair, is infrequent. Here, we report the case of a 22-year-old male patient with a history of congenital diaphragmatic disease initally treated with surgery on the second day of life who presented class I dyspnea and gastroesophageal reflux. A left diaphragmatic hernia with a hernia sac containing the spleen, colon, tail of pancreas and left adrenal gland. The patient underwent surgical repair via a left subcostal incision; the hernia sac was reduced, the diaphragmatic defect was repaired with a mesh and the Ladd procedure was performed due to the diagnosis of intestinal malrotation.

Prognosis of mortality and evolution in pancreatoduodenal trauma in patients with wound by projectile of firearm.

BACKGROUND: The wounds caused by the firearm projectile are published to date in a public health problem in the world. As an example, we mentioned the injuries caused by firearms are the first cause of death in the age group between 1 to 19 years in the United States, as in Mexico. OBJECTIVE: Analysis of the prognostic factors of mortality and evaluation of the evolution in patients with TPD due to abdominal HPPAF. METHOD: Retrospective, observational, descriptive study. Helped by 49 clinical files of patients who were admitted to the department of surgery of the University Hospital José Eleuterio González, between 2011 to 2015 and whose diagnosis was due to pancreatic trauma (TP), duodenal trauma (TD) or pancreatoduodenal trauma (TPD) by wounds caused by the firearm projectile. RESULTS: During a collection period of 5 years, a total of 49 clinical records applicable to the study were obtained according to the inclusion criteria, of which 36 (73%) suffered only from TD, 37 (75%) from TP and 24 (49%) about TPD. Significant differences were obtained for mortality associated with TD and TPD, but not for TP. The most affected organ as a lesion associated with a TPD was the liver, followed by thoracic structures and the stomach. The most significant risk factor for mortality was a prolonged stay in the intensive care unit. CONCLUSIONS: Data obtained are consistent with those consulted, providing new reproducible statistics for future studies regarding the increasing violence in our country and around the world.

ANTECEDENTES: Las heridas por proyectil de arma de fuego constituyen un problema de salud pública en el mundo. Como ejemplo mencionamos que este tipo de lesiones son la primera causa de muerte en el grupo de edad de 1 a 19 años en los EE.UU., al igual que en México. OBJETIVO: Análisis de los factores pronósticos de mortalidad y evaluación de la evolución en pacientes con TPD por HPPAF abdominal. MÉTODO: Estudio retrospectivo, observacional y descriptivo, realizado con 49 expedientes clínicos de pacientes que fueron admitidos en el departamento de cirugía del Hospital Universitario José Eleuterio González entre los años 2011 y 2015, cuyo diagnostico fue herida por proyectil de arma de fuego con trauma pancreático (TP), duodenal (TD) o pancreatoduodenal (TPD). RESULTADOS: Durante un periodo de recolección de 5 años se obtuvieron 49 expedientes clínicos aplicables al estudio según los criterios de inclusión, de los cuales 36 pacientes (73%) sufrieron únicamente TD, 37 (75%) TP y 24 (49%) TPD. Se obtuvieron diferencias significativas para la mortalidad asociada a TD y TPD, pero no para TP. El órgano más afectado como lesión asociada a un TPD fue el hígado, seguido de las estructuras torácicas y el estómago. El factor de riesgo para mortalidad más significativo fue una estancia prolongada en la unidad de cuidados intensivos. CONCLUSIONES: Los datos conseguidos concuerdan con los consultados, otorgando nueva estadística reproducible para futuros estudios respecto a la violencia creciente en nuestro país y alrededor del mundo.

Duodenal injury in blunt abdominal trauma. Case report and literature review.

There are few reported cases of small bowel injury due to blunt abdominal trauma. We describe the clinical presentation and surgical management of these lesions. This is the clinical case of a polytraumatized male with a duodenal injury IIID3 according to AAST, who underwent resection of the intestinal segment with duodeno-duodenum anastomosis with favorable results. The infrequent presentation of injuries to the small intestine due to blunt trauma may lead the clinician to overlook the need for intentional interrogation about the kinematics of the trauma, while at the same time neglecting the taking of complementary diagnostic imaging studies, this because of a lack of clinical suspicion. It is important to analyze the patient's context, which will allow us to assess the need to delve into diagnostic studies in order to optimize their treatment.

Existen pocos casos notificados de lesión de intestino delgado por traumatismo contuso abdominal. Se describen la presentación clínica y el tratamiento quirúrgico de dichas lesiones, un caso clínico de un paciente masculino politraumatizado con lesión duodenal IIID3 según la AAST, objeto de resección de segmento intestinal con anastomosis duodenoduodenal terminoterminal con resultados favorables. La presentación infrecuente de lesiones de intestino delgado por traumatismo contuso puede llevar al clínico a soslayar la necesidad de un interrogatorio intencionado acerca de la cinemática del traumatismo y también de los estudios de imagen complementarios diagnósticos debido a la falta de sospecha clínica. Es importante analizar el contexto del paciente para valorar la necesidad de profundizar en estudios diagnósticos y optimizar el tratamiento.

Genetic alterations of triple negative breast cancer (TNBC) in women from Northeastern Mexico.

Triple negative breast cancer (TNBC) is a subtype of breast cancer of heterogeneous nature that is negative for estrogen receptor (ER), progesterone receptor (PR) and growth factor human epidermal 2 (HER2) following immunohistochemical analysis. TNBC is frequently characterized by relapse and reduced survival. To date, there is no targeted therapy for this type of cancer. Chemotherapy, radiotherapy, and surgery remain as the standard treatments options. The lack of a target therapy and the heterogeneity of TNBC highlight the need to seek new therapeutic options. In this study, fresh tissue samples of TNBC were analyzed with a panel of 48 driver genes (212 amplicons) that are likely to be therapeutic targets. We found intron variants, missense, stop gained and splicing variants in TP53, PIK3CA and FLT3 genes. Interestingly, all the analyzed samples had at least two variants in the TP53 gene, one being a drug response variant, rs1042522, found in 94% of our samples. We also found seven additional variants not previously reported in the TP53 gene, to the best of our knowledge, with probable deleterious characteristics of the tumor suppressor gene. We found four genetic variants in the PIK3CA gene, including two missense variants. The rs2491231 variant in the FLT3 gene was identified in 84% (16/19) of the samples, which not yet reported for TNBC, to the best of our knowledge. In conclusion, genetic variants in TP53 were found in all TNBC tumors, with rs1042522 being the most frequent (94% of TNBC biopsies), which had not been previously reported in TNBC. Also, we found two missense variants in the PIK3CA gene. These results justify the validation of these genetic variants in a large cohort, as well as the extensive study of their impact on the prognosis and therapy management of TBNC.

DNA vaccine encoding human papillomavirus antigens flanked by a signal peptide and a KDEL sequence induces a potent therapeutic antitumor effect.

Cellular immune responses play a critical role in the eradication of intracellular infections and malignant cells through the recognition and subsequent removal of the infection or malignant cells. Effective antigen presentation is crucial for stimulating the immune system against malignant cells. Calreticulin (CRT) has been used to improve antigen presentation. However, CRT overexpression has been previously associated with the development of pancreatic and breast cancer. The import and retention signals of CRT in the endoplasmic reticulum (ER) can be used to overcome CRT overexpression. The present study describes the potent antitumor effect of a DNA vaccine encoding human papillomavirus type 16 E6 and E7 antigens flanked by ER import and retention signals (SP-E6E7m-KDEL). The effect of this vaccine was compared with that of E6 and E7 antigens fused to human full-length CRT (hCRT-E6E7m). In the present study, the effectiveness of SP-E6E7m-KDEL for inducing an interferon-γ antigen-specific, response and its therapeutic effect against tumors was demonstrated, which was as effective as immunization against those antigens fused to CRT. This simplified strategy, using ER import and retention signal peptides to direct antigens to this organelle, provides an efficient alternative to traditional vaccines and, more importantly, a safe and potent system to induce a therapeutic antitumor response.

Invasion of TC-1 cells to skeletal muscle fibers protect them from peroxisomicine A1 (T-514) treatment in a murine model of cancer.

T-514 or Peroxisomicine A1 (PA1) is a toxin isolated from plants of genus Karwinskia. In vitro studies described selective toxicity of PA1 on malignant cell lines. A toxic effect of PA1 on TC-1 cells in vivo was reported. The objective was to evaluate the effect of PA1 over invasion of TC-1 cells to muscle fibers in vivo. TC-1 cells were implanted in 36 mice divided in two groups (n: 18): treated with PA1 or with vehicle, a control group was included. At 10 days, nine mice of each group were euthanized. TC-1 implant site was analyzed by light and electron microscopy, a morphometric study was also performed. Remaining mice were used to evaluate tumor growth and survival time. Results show tumor cells between muscle fibers, with diminution in diameter, change in the staining pattern, loss of continuity of external lamina, and sarcoplasm with tumor cells. Statistically difference was observed between treated group vs control group. PA1 decreased tumor growth and increased the survival time in treated mice. The degree of resistant activity, aggressiveness, and invasiveness of TC-1 cells described in present work; should be taken into account in studies that evaluate effectiveness of therapies using this cancer model.

Histopathological alterations in the striatum caused by Karwinskia humboldtiana (Buckthorn) fruit in an experimental model of peripheral neuropathy.

The accidental ingestion of Karwinskia humboldtiana (Kh) fruit in humans and animals causes chronic or acute intoxication. Acute poisoning induces respiratory failure that progresses rapidly to death. Studies in animals intoxicated with Kh describe lesions in cerebral cortex, cerebellum, spinal cord, hippocampus and caudate nucleus. Kh intoxication in Wistar rats models the sub-lethal clinical phase observed in humans. Considering these reports, the present study analyzed the histopathological alterations within the striatum following experimental Kh intoxication. Twenty Wistar rats were divided into three groups (n =5) and were intoxicated with Kh fruit. A control group (n =5) was included. Animals were euthanized at several time points (48, 58 and 170 days post-intoxication). The brain was collected, divided and processed for conventional histology or electron microscopy. Sections were stained with hematoxylin and eosin, cresyl violet, Klüver-Barrera, and toluidine blue. Immunolabeling was performed for glial cells in the striatum, and the samples were analyzed with light microscopy. Morphometric and statistical analyses were performed. In control group, neurons, axon bundles and neuropil had a normal appearance. At 48 days, hyperchromic neurons with apparent decreased size were observed interspersed among the normal neurons. At 58 days, we observed an increased number of hyperchromic neurons and disorganization of the myelin sheath and neuropil. At 170 days, these alterations persisted in the paralysis group. In treated groups, we observed signs of gliosis and increased axonal diameters. This study is the first report that describes the histopathological alterations within the striatum caused by chronic intoxication with Kh fruit in the Wistar rat.

CXCL10/XCL1 fusokine elicits in vitro and in vivo chemotaxis.

Fusokines are proteins formed by the fusion of two cytokines. They have greater bioavailability and therapeutic potential than individual cytokines or a combination of different cytokines. Interferon-gamma-inducible protein 10 (CXCL10) and lymphotactin (XCL1) are members of the chemotactic family of cytokines, which induce tumor regression by eliciting immune-system cell chemotaxis. We engineered a replication-deficient adenoviral system expressing CXCL10/XCL1 fusokine (Ad FIL) and assessed its chemotactic response in vitro and in vivo. The CXCL10/XCL1 fusokine elicited a greater chemotactic effect in IL-2 stimulated lymphocytes than individual or combined cytokines in vitro. CXCL10/XCL1 fusokine biological activity was demonstrated in vivo by intratumoral chemoattraction of CXCR3+ cells. Thus, this novel CXCL10/XCL1 fusokine may represent a potential tool for gene therapy treatment of cancer and other illnesses that require triggering immune-system cell recruitment.