[Rectal metastasis of a resected urothelial bladder cancer]. / Metástasis rectal de carcinoma urotelial de vejiga resecado.

We present the case of a female patient with a history of high-grade urothelial carcinoma of the bladder with secondary lymph node and bone involvement, who presented with hematochezia, tenesmus and rectal pain one year after her oncological surgery. The abdomen and pelvis magnetic resonance image showed a 5 cm solid rectal lesion that stenosed the lumen and crossed the peritoneum, 6 cm away from the anal margin. The histology of this lesion reported an urothelial metastasis at the level of the lower rectum according to the patient's history. This case identifies an atypical evolution of urothelial carcinomas (UC), highlighting an unusual route of distant metastasis. UC can, on rare occasions, metastasize to the rectum, usually in advanced or recurrent cases of the disease. As the literature available on this topic is scarce, it is crucial to highlight the importance of maintaining high suspicion in patients with a history of urothelial carcinoma and urinary/rectal symptoms (rectal pain and urgency, suprapubic pain, urinary and fecal incontinence).

Se presenta el caso de una paciente con antecedentes de carcinoma urotelial de vejiga de alto grado con compromiso secundario ganglionar y óseo, la cual presentó cuadro de hematoquecia, tenesmo y dolor rectal un año después de su cirugía oncológica. La resonancia magnética de abdomen y pelvis, demostró una lesión sólida rectal de 5 cm de longitud que estenosaba la luz y atravesaba el peritoneo, a 6 cm del margen anal. La anatomía patológica de dicha lesión, informó una metástasis urotelial a nivel del recto inferior en concordancia con el antecedente de la paciente. Este caso identifica una evolución atípica de carcinomas uroteliales (CU), destacando una ruta inusual de metástasis a distancia. Los CU pueden, en raras ocasiones, hacer metástasis rectales, generalmente en casos avanzados o recurrentes de la enfermedad. Al ser escasa la bibliografía disponible sobre dicho tema, cabe destacar la importancia de mantener un alto índice de sospecha en pacientes con antecedentes de carcinoma urotelial y síntomas urinarios/rectales (dolor y tenesmo rectal, dolor suprapúbico, incontinencia urinaria y fecal).

Metástasis rectal de carcinoma urotelial de vejiga resecado / Rectal metastasis of a resected urothelial bladder cancer

Resumen Se presenta el caso de una paciente con antecedentes de carcinoma urotelial de vejiga de alto grado con compromiso secundario ganglionar y óseo, la cual presentó cuadro de hematoquecia, tenesmo y dolor rectal un año después de su cirugía oncológica. La resonancia magnética de abdomen y pelvis, demos tró una lesión sólida rectal de 5 cm de longitud que estenosaba la luz y atravesaba el peritoneo, a 6 cm del margen anal. La anatomía patológica de dicha lesión, informó una metástasis urotelial a nivel del recto inferior en concordancia con el antecedente de la paciente. Este caso identifica una evolución atípica de carcinomas uroteliales (CU), destacando una ruta inusual de metástasis a distancia. Los CU pueden, en raras ocasiones, hacer metástasis rectales, generalmente en casos avanzados o recurrentes de la enfermedad. Al ser escasa la bibliografía disponible sobre dicho tema, cabe destacar la importancia de mantener un alto índice de sospecha en pacientes con antecedentes de carcinoma urotelial y síntomas urinarios/rectales (dolor y tenesmo rectal, dolor suprapúbico, incontinencia urinaria y fecal).

Abstract We present the case of a female patient with a history of high-grade urothelial carcinoma of the bladder with secondary lymph node and bone involvement, who presented with hematochezia, tenesmus and rectal pain one year after her oncological surgery. The abdomen and pelvis magnetic resonance image showed a 5 cm solid rectal lesion that stenosed the lumen and crossed the peritoneum, 6 cm away from the anal margin. The histology of this lesion reported an urothelial metastasis at the level of the lower rectum according to the patient's history. This case identifies an atypical evolution of urothelial carcinomas (UC), highlighting an unusual route of distant metastasis. UC can, on rare occasions, metastasize to the rectum, usually in advanced or recurrent cases of the disease. As the literature available on this topic is scarce, it is crucial to highlight the importance of maintaining high suspicion in patients with a history of urothelial carcinoma and urinary/rectal symptoms (rectal pain and urgency, suprapubic pain, urinary and fecal incontinence).

Angiotensin II type 1 receptor is involved in hypertension and vascular alterations caused by environmental toxicant hexachlorobenzene.

Environmental hexachlorobenzene (HCB) increases blood pressure (BP) in female rats, causing alterations in arterial structure and function. Here we study the role of Angiotensin II receptor type 1 (AT1) in HCB-induced hypertension through the use of AT1 antagonist losartan. HCB-treated male rats showed a 22.7% increase in BP which was prevented by losartan. Losartan blocked HCB-induced changes in arterial morphology (decreased aorta cell number and increased wall thickness). Losartan also prevented HCB-induced alterations in artery relaxation by acetylcholine and nitroprusside but not the reduction in the maximum contraction by phenylephrine. Losartan rescued arterial molecular alterations caused by HCB (i.e. an increase in TGF-ß1 and AT1 expression and a decrease in eNOS expression and nitrite levels) and reduced hydrogen sulfide plasma concentration. In conclusion: in this work we demonstrate that AT1 activity is involved in HCB effects on the vascular system leading to hypertension.

TGF-ß1 mediates cell proliferation and development of hepatocarcinogenesis by downregulating deiodinase 1 expression.

Hepatocellular carcinoma (HCC) is the most common primary liver tumor. Hexachlorobenzene (HCB) is an endocrine disruptor and a liver tumor promoter. Deregulation of thyroid hormone (TH) homeostasis may play a significant role in early neoplastic transformation. The aim of this study was to evaluate the relation between TH metabolism and the regulation of cell growth in an in vivo and in vitro model. We examined the role of transforming growth factor-ß1 (TGF-ß1) on TH deiodinase expression and hepatocyte proliferation. An initiation (DEN)/promotion (HCB) tumor model from rat liver and HepG2 cells were used. We evaluated PCNA, p21, p27, SMAD2/3, TGF-ß1, deiodinase 1 (D1), D3, protein expression levels; D1 and D3 mRNA expression; TH and TGF-ß1, D1, D3, and GST-P protein levels in focal/non-focal areas. In vivo, HCB decreased triiodothyronine (T3) and D1 mRNA levels and increased thyroxine (T4) and D3 mRNA levels in liver from DEN+HCB vs. DEN group. HCB increased protein levels from D3, TGF-ß1, and PCNA and decreased D1 in focal-areas. In vitro, HCB increased PCNA, pSMAD 2/3, and TGF-ß1 protein levels and mRNA expression and decreased p21 and p27 protein levels. Exogenous T3 treatment prevent HCB induced molecular alterations related to hepatocyte proliferation whereas T4 did not have any effect. These effects were prevented by using a TGF-ß1 receptor II inhibitor. Results suggest that alteration of TH homeostasis, through D1 function, play a key role in hepatocyte proliferation and that TGF-ß1-SMAD pathway is involved in this process confirming their role in early neoplastic transformation in HCC.

El hepatocarcinoma (HCC) es un tumor hepático primario. El hexaclorobenceno (HCB) es un disruptor endocrino y un promotor de tumores hepáticos. La desregulación de la homeostasis de las hormonas tiroideas (HT) puede ser un proceso importante para la transformación neoplásica temprana. Nuestro objetivo fue evaluar la relación entre el metabolismo de las HT y la regulación de la proliferación celular. Se utilizó un modelo tumoral de iniciación (DEN)/promoción (HCB) de hígado de rata (in vivo) (DEN/HCB) y células HepG2 (in vitro). Evaluamos los niveles de PCNA, p21, p27, SMAD2/3, TGF-ß1, D1, D3, ARNm de D1 y D3, HT y los niveles de TGF-ß1, D1, D3 y GST-P en áreas focales/no focales. In vivo, HCB disminuyó los niveles de T3 y ARNm de la D1 y aumentó los niveles de T4 y ARNm de D3 del grupo DEN + HCB frente al grupo DEN. El HCB aumentó los niveles de D3, TGF-ß1 y PCNA y disminuyó el D1 en las áreas focales. In vitro, HCB aumentó los niveles de PCNA, pSMAD 2/3 y TGF-ß1 y la expresión de ARNm mientras que disminuyó los niveles de p21 y p27. El tratamiento con T3 exógeno previno las alteraciones moleculares relacionadas con la proliferación hepatocitaria. Estos efectos se evitaron utilizando un inhibidor del receptor II de TGF-ß1. Los resultados sugieren que la alteración de la homeostasis de HT, a través de la D1 y la vía TGF-ß1-SMAD, juega un papel clave en la proliferación celular y en las transformaciones neoplásicas tempranas en el HCC.

TGF-ß1 mediates cell proliferation and development of hepatocarcinogenesis by downregulating deiodinase 1 expression / La desregularización de la deiodinasa 1, mediada por TGF-b1, impulsa la proliferación celular y el desarrollo de hepatogénesis

Abstract Hepatocellular carcinoma (HCC) is the most common primary liver tumor. Hexachlorobenzene (HCB) is an endocrine disruptor and a liver tumor promoter. Deregulation of thyroid hormone (TH) homeostasis may play a significant role in early neoplastic transformation. The aim of this study was to evaluate the relation between TH metabolism and the regulation of cell growth in an in vivo and in vitro model. We examined the role of transforming growth factor-β1 (TGF-β1) on TH deiodinase expression and hepatocyte proliferation. An initiation (DEN)/promotion (HCB) tumor model from rat liver and HepG2 cells were used. We evaluated PCNA, p21, p27, SMAD2/3, TGF-β1, deiodinase 1 (D1), D3, protein expression levels; D1 and D3 mRNA expression; TH and TGF-β1, D1, D3, and GST-P protein levels in focal/non-focal areas. In vivo, HCB decreased triiodothyronine (T3) and D1 mRNA levels and increased thyroxine (T4) and D3 mRNA levels in liver from DEN+HCB vs. DEN group. HCB increased protein levels from D3, TGF-β1, and PCNA and decreased D1 in focal-areas. In vitro, HCB increased PCNA, pSMAD 2/3, and TGF-β1 protein levels and mRNA expression and decreased p21 and p27 protein levels. Exogenous T3 treatment prevent HCB induced molecular alterations related to hepatocyte proliferation whereas T4 did not have any effect. These effects were prevented by using a TGF-β1 receptor II inhibitor. Results suggest that alteration of TH homeostasis, through D1 function, play a key role in hepatocyte proliferation and that TGF-β1-SMAD pathway is involved in this process confirming their role in early neoplastic transformation in HCC.

Resumen El hepatocarcinoma (HCC) es un tumor hepático primario. El hexaclorobenceno (HCB) es un disruptor endocrino y un promotor de tumores hepáticos. La desregulación de la homeostasis de las hormonas tiroideas (HT) puede ser un proceso importante para la transformación neoplásica temprana. Nuestro objetivo fue evaluar la relación entre el metabolismo de las HT y la regulación de la prolifera ción celular. Se utilizó un modelo tumoral de iniciación (DEN)/promoción (HCB) de hígado de rata (in vivo) (DEN/ HCB) y células HepG2 (in vitro). Evaluamos los niveles de PCNA, p21, p27, SMAD2/3, TGF-β1, D1, D3, ARNm de D1 y D3, HT y los niveles de TGF-β1, D1, D3 y GST-P en áreas focales/no focales. In vivo, HCB disminuyó los niveles de T3 y ARNm de la D1 y aumentó los niveles de T4 y ARNm de D3 del grupo DEN + HCB frente al grupo DEN. El HCB aumentó los niveles de D3, TGF-β1 y PCNA y disminuyó el D1 en las áreas focales. In vitro, HCB aumentó los niveles de PCNA, pSMAD 2/3 y TGF-β1 y la expresión de ARNm mientras que disminuyó los niveles de p21 y p27. El tratamiento con T3 exógeno previno las alteraciones moleculares relacionadas con la proliferación hepatocitaria. Estos efectos se evitaron utilizando un inhibidor del receptor II de TGF-β1. Los resultados sugieren que la alteración de la homeostasis de HT, a través de la D1 y la vía TGF-β1-SMAD, juega un papel clave en la proliferación celular y en las transformaciones neoplásicas tempranas en el HCC.

[Lung cancer diagnosed by transesophageal ecoendoscopy and fine needle aspiration biopsy]. / Cáncer de pulmón diagnosticado mediante ecoendoscopía transesofágica y biopsia por punción con aguja fina.

Lung cancer is one of the leading causes of death worldwide. Pulmonary nodules located in the vicinity of the mediastinum, retrocardiac, near the aorta or pulmonary vessels, and in front of the spine, may be difficult to access through a percutaneous or bronchoscopic approach. Fine needle aspiration/biopsy guided by transesophageal echoendoscopy (EUS-FNA/FNB) is a minimally invasive method with low morbidity that could allow access to lesions in these places. We present the case of a patient with a solitary pulmonary nodule, in which the diagnosis of lung cancer was obtained by EUS-FNA/FNB.

El cáncer de pulmón es la principal causa de muerte por cáncer en todo el mundo. Los nódulos pulmonares ubicados en proximidad al mediastino, retrocardíacos, cercanos a grandes vasos o por delante de la columna vertebral pueden resultar de difícil acceso por vía percutánea o broncoscópica. La punción aspiración/biopsia con aguja fina guiada por ecoendoscopía transesofágica (EUS-FNA/FNB) es un método mini invasivo con baja morbilidad que permitiría acceder a estas localizaciones. Presentamos el caso de un paciente con nódulo pulmonar solitario, en el que se obtuvo el diagnóstico de cáncer de pulmón mediante EUS-FNA/FNB.

Cáncer de pulmón diagnosticado mediante ecoendoscopia transesofágica y biopsia por punción con aguja fina / Lung cancer diagnosed by transesophageal ecoendoscopy and fine needle aspiration biopsy

El cáncer de pulmón es la principal causa de muerte por cáncer en todo el mundo. Los nódulos pulmonares ubicados en proximidad al mediastino, retrocardíacos, cercanos a grandes vasos o por delante de la columna vertebral pueden resultar de difícil acceso por vía percutánea o broncoscópica. La punción aspiración/biopsia con aguja fina guiada por ecoendoscopía transesofágica (EUS-FNA/FNB) es un método mini invasivo con baja morbilidad que permitiría acceder a estas localizaciones. Presentamos el caso de un paciente con nódulo pulmonar solitario, en el que se obtuvo el diagnóstico de cáncer de pulmón mediante EUS-FNA/FNB.

Lung cancer is one of the leading causes of death worldwide. Pulmonary nodules located in the vicinity of the mediastinum, retrocardiac, near the aorta or pulmonary vessels, and in front of the spine, may be difficult to access through a percutaneous or bronchoscopic approach. Fine needle aspiration/biopsy guided by transesophageal echoendoscopy (EUS-FNA/FNB) is a minimally invasive method with low morbidity that could allow access to lesions in these places. We present the case of a patient with a solitary pulmonary nodule, in which the diagnosis of lung cancer was obtained by EUS-FNA/FNB.

Potential Molecular Targets of Statins in the Prevention of Hepatocarcinogenesis.

Hepatocellular carcinoma (HCC) represents 90% of liver tumors. Statins, may reduce the incidence of various tumors, including HCC. Antitumoral activities may be mediated by changes in transforming growth factor-beta (TGF-ß1) and thyroid hormones (TH) regulation. INTRODUCTION AND AIM: Hepatocellular carcinoma (HCC) represents 90% of liver tumors. Statins, may reduce the incidence of various tumors, including HCC. Antitumoral activities may be mediated by changes in transforming growth factor-beta (TGF-ß1) and thyroid hormones (TH) regulation. Aim. The aim of our study is to establish the statins mechanism of action and the potential key molecules involved in an in vivo and in vitro HCC model. MATERIALS AND METHODS: We used two models: in vivo (in rats) using diethylnitrosamine (DEN) and hexachlorobenzene (HCB) to develop HCC. We analyzed cell proliferation parameters (proliferating cel nuclear antigen, PCNA) and cholesterol metabolism (hydroxy-methylglutaryl-CoA reductase, HMGCoAR). In vitro (Hep-G2 cells) we evaluated the effects of different doses of Atorvastatin (AT) and Simvastatin (SM) on HCB induced proliferation and analyzed proliferative parameters, cholesterol metabolism, TGF-ß1 mRNA, c-Src and TH levels. RESULTS: In vivo, we observed that cell proliferation significantly increased as well as cholesterol serum levels in rats treated with HCB. In vitro, we observed the same results on PCNA as in vivo. The statins prevented the increase in HMG-CoAR mRNA levels induced by HCB, reaching levels similar to controls at maximum doses: AT (30 µM), and SM (20 µM). Increases in PCNA, TGF-ß1, and pc-Src, and decreases in deiodinase I mRNA levels induced by HCB were not observed when cells were pre-treated with AT and SM at maximum doses. CONCLUSION: Statins can prevent the proliferative HCB effects on Hep-G2 cells. TGF-ß1, c-Src and TH may be the statins molecular targets in hepatocarcinogenesis.

Environmental pollutant hexachlorobenzene induces hypertension in a rat model.

Hexachlorobenzene (HCB) is a dioxin-like environmental pollutant, widely distributed in the environment. New research links exposure to high levels of persistent organic environmental toxicants to cardiovascular disease, however little is known about the effect of HCB on vascular function and on blood pressure. The purpose of the present study was to evaluate biochemical and cardiovascular changes resulting from subchronic HCB exposure. Adult female Sprague-Dawley rats were treated with vehicle or HCB (5 or 500 mg/kg b.w) for 45 days. Systolic blood pressure (BP), recorded by tail cuff plethysmography, was significantly increased at 35, 40 and 45 days of 500 mg/kg HCB-treatment. HCB (500 mg/kg) increased arterial thickness, while both 5 and 500 mg/kg HCB decreased proliferating cell nuclear antigen (PCNA) protein levels and cellular nuclei in abdominal aortas indicating a hypertrophic process. Also, aortas from both groups of HCB-treated rats presented higher sensitivity to noradrenalin (NA) and a significant decrease in maximum contractile response. Arteries from 500 mg/kg HCB-treated rats showed a significant increase in the levels of transforming growth factor-ß1 (TGF-ß1) mRNA and angiotensin II type1 receptor (AT1), and a significant decrease in estrogen receptor alpha (ERα), endothelial nitric oxidide synthase (eNOS) protein expression and deiodinase II (DII) mRNA levels. In conclusion, we have demonstrated for the first time that subchronic HCB administration significantly increases BP and alters associated cardiovascular parameters in rats. In addition, HCB alters the expression of key vascular tissue molecules involved in BP regulation, such as TGF-ß1, AT1, ERα, eNOS and DII.