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Liver metastasis of colon cancer is a very common clinical entity. Resective surgery can be used to improve the overall survival and disease-free. The problem is that major resections are associated with hepatic failure caused by an inadequate residual volume. Chemotherapy with diagrams as FOLFOX, FOLFIRI associated with antibodies such as bevacizumab, cetuximab or panitumumable added an important role in the conversion of unresectable to resectable tumors. Another widely used technique is portal vein ligation in a first surgical procedure, that generates left hepatic growth, to perform the resection in a second surgical procedure. The liver hypertrophy is achieved in a period of 2 months. The latest new technical procedure is the association of the ligation portal to the liver partition of the hepatic parenchyma without resection, which allows a segmental hypertrophy of the liver remnant between 7 to 10 days. This technique is called ALPPS. Radiofrecuency also has a role in the treatment of liver metastases. However,it is secondary.

La metástasis hepáticas del cáncer de colon es una entidad clínica muy frecuente. La cirugía resectiva permite mejorar la sobrevida global y libre de enfermedad. El problema es que grandes resecciones se asocian a insuficiencia hepática por un inadecuado volumen residual. La quimioterapia con esquemas como FOLFOX, FOLFIRI asociada a anticuerpos como bevacizumab, cetuximab o panitumumable agregan un rol importante en la conversión de tumores irresecables a resecables. Otra técnica utilizada es la ligadura portal en un primer tiempo, que genera crecimiento hepático izquierdo, para realizar la resección en un segundo tiempo quirúrgico. La hipertrofia hepática se logra en un período de 2 meses. La última novedad técnica es la asociación de la ligadura portal a la transección del parénquima hepático sin resección, lo que permite una hipertrofia segmentaria del hígado remanente entre 7 a 10 días. Esta técnica se denomina ALPPS. La radiofrecuencia también tiene un rol en el tratamiento de las metástasis hepáticas, aunque este es secundario.

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The occurrence of postoperative jaundice should encourage the surgeon to review the wide spectrum of possible causes of jaundice and perform detailed history, physical examination and laboratory tests to define the causes, and take the measures to treat the patient properly. We also emphasize the need to prevent the presence of residual stones in the bile duct and bile duct iatrogenic injuries. This paper describe the possible causes of postoperative jaundice and current recommendations for adequate treatment.

La aparición de ictericia en el postoperatorio debe alertar al cirujano y llevarlo a revisar el gran espectro de causas posibles del cuadro. Se debe realizar una anamnesis y examen físico detallado y complementarlo con exámenes de laboratorio e imágenes según el caso. Además, se insiste en la necesidad de prevenir la presencia de cálculos residuales en colédoco y lesiones iatrogénicas de vía biliar. Se revisan las causas posibles de ictericia postoperatoria y las recomendaciones actuales de manejo.

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The cytotoxic activity of amino (3a-e), aza-1-antraquinone (4a-e) lapachol derivatives against Ehrlich carcinoma and human K562 leukemia cells was investigated. Cell viability was determined using MTT assay, after 48 (Ehrlich) or 96 h (K562) of culture, and vincristine (for K562 leukemia) and quercetin (for Ehrlich carcinoma) were used as positive controls. The results showed dose-dependent growth-inhibiting activities and that the amino derivatives were active against the assayed cells, whereas the 4a-e derivatives were not. The allylamine derivative 3a was the most active against Ehrlich carcinoma, with IC50 = 16.94 ± 1.25 muM, and against K562 leukemia, with IC50 = 14.11 ± 1.39 muM. The analogous lawsone derivative, 5a, was also active against Ehrlich carcinoma (IC50 = 23.89 ± 2.3 muM), although the 5d and 5e derivatives showed lower activity. The interaction between 3a-d and calf thymus DNA was investigated by fluorimetric titration and the results showed a hyperchromic effect indicating binding to DNA as presented of ethidium bromide, used as positive control. The inhibitory action on DNA-topoisomerase II-a was also evaluated by a relaxation assay of supercoiled DNA plasmid, and the etoposide (200 muM) was used as positive control. Significant inhibitory activities were observed for 3a-d at 200 muM and a partial inhibitory action was observed for lapachol and methoxylapachol.

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RESUMO

The cytotoxic activity of amino (3a-e), aza-1-antraquinone (4a-e) lapachol derivatives against Ehrlich carcinoma and human K562 leukemia cells was investigated. Cell viability was determined using MTT assay, after 48 (Ehrlich) or 96 h (K562) of culture, and vincristine (for K562 leukemia) and quercetin (for Ehrlich carcinoma) were used as positive controls. The results showed dose-dependent growth-inhibiting activities and that the amino derivatives were active against the assayed cells, whereas the 4a-e derivatives were not. The allylamine derivative 3a was the most active against Ehrlich carcinoma, with IC50 = 16.94 +/- 1.25 microM, and against K562 leukemia, with IC50 = 14.11 +/- 1.39 microM. The analogous lawsone derivative, 5a, was also active against Ehrlich carcinoma (IC50 = 23.89 +/- 2.3 microM), although the 5d and 5e derivatives showed lower activity. The interaction between 3a-d and calf thymus DNA was investigated by fluorimetric titration and the results showed a hyperchromic effect indicating binding to DNA as presented of ethidium bromide, used as positive control. The inhibitory action on DNA-topoisomerase II-a was also evaluated by a relaxation assay of supercoiled DNA plasmid, and the etoposide (200 microM) was used as positive control. Significant inhibitory activities were observed for 3a-d at 200 microM and a partial inhibitory action was observed for lapachol and methoxylapachol.

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Previous work has demonstrated that N-N'-diphenyl-R-benzamidine was highly effective against Leishmania amazonensis promastigotes/axenic amastigotes and Trypanosoma evansi trypomastigotes and the compound with a methoxy substituent, was the most effective derivative in the parasite-macrophage interaction. Comparative analysis of the nitric oxide (NO) released from the culture infection's supernatant showed the amidine to be less effective than pentamidine Isethionate as a reference drug. Additionally, in order to verify if the methoxylated derivative interferes with NO production by L. amazonensis, the effect of the amidine on the constitutive nitric oxide synthase (cNOS) purified from parasites, was examined, but demonstrated less activity in comparison with the reference drug. This data contributes to studies concerning the metabolic targets present in Leishmania parasites for leishmanicidal drugs.

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Diffuse pulmonary ossification is a rare entity that presents with the formation of mature bone in the pulmonary parenchyma and is associated with diffuse and chronic lung disease, heart disease, or other system disorders. Diffuse pulmonary ossification is usually a postmortem finding by the pathologist. In the case we report, the diagnosis was established by open lung biopsy. The patient was a 79-year-old man with dyspnea, dry cough, and weight loss. He had been a smoker. A chest x-ray revealed reticulonodular bilateral pulmonary infiltrates. Computed tomography revealed interstitial disease predominantly in the septum with multiple cavitations that tended to form honeycomb patterns. Pleural thickening, retraction of the parenchyma, and bilateral fibrosis were also visible. A clinical diagnosis of interstitial fibrosis was established and the patient s course was unfavorable. An open lung biopsy was performed. The lung tissue specimens revealed zones with collapsed alveoli and others with emphysema, some of which produced secretion and erythrocytic extravasation. Interstitial vascular congestion was apparent; bronchioles presented mononuclear and some polymorphonuclear inflammatory infiltrates. Noteworthy was the presence of predominantly interstitial, multicentric foci of osseous trabeculae --some of which included adipose bone marrow. Diffuse pulmonary ossification is usually an incidental finding in autopsies of patients with a history of diffuse chronic pulmonary disease, but it is an unusual diagnosis in living patients. Diffuse pulmonary ossification is of no prognostic significance in pulmonary fibrosis. It is a marker of the chronicity and/or severity of the fibrosis.

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The structural characteristics of mesoionic compounds, which contain distinct regions of positive and negative charges associated with a poly-heteroatomic system, enable them to cross cellular membranes and interact strongly with biomolecules. Potential biological applications have been described for mesoionic compounds. 1,3,4-Thiadiazolium mesoionic compound (MI-D), a new mesoionic compound, has been demonstrated to be extremely cytotoxic to B16-F10 murine melanoma cells when compared to fotemustine and dacarbazine, drugs of reference in melanoma treatment protocols, describing inhibition of tumours grown in vitro and in vivo. We now evaluate the effects of mesoionic compound MI-D on different human melanoma cell lines. The drug decreased the viability and proliferation of MEL-85, SK-MEL, A2058 and MEWO cell lines in vitro, showing a considerable cytotoxic activity on these human cells. Adhesion of MEL-85 cells was evaluated in the presence of the drug using different extracellular matrix (ECM) constituents. MI-D decreased MEL-85 adhesion to laminin, fibronectin and matrigel. The morphology and actin cytoskeleton organisation of MEL-85 cells were also modified on MI-D treatment. These results on human melanoma cell lines indicate that MI-D is a very encouraging drug against melanoma, a tumour that is extremely resistant to chemotherapy.

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Topoisomerase inhibitors are agents with anticancer activity. 7"-O-Methyl-agathisflavone (I) and amentoflavone (II) are biflavonoids and were isolated from the Brazilian plants Ouratea hexasperma and O. semiserrata, respectively. These biflavonoids and the acetyl derivative of II (IIa) are inhibitors of human DNA topoisomerases I at 200 microM, as demonstrated by the relaxation assay of supercoiled DNA, and only agathisflavone (I) at 200 microM also inhibited DNA topoisomerases II-alpha, as observed by decatenation and relaxation assays. The biflavonoids showed concentration-dependent growth inhibitory activities on Ehrlich carcinoma cells in 45-h culture, assayed by a tetrazolium method, with IC50 = 24 +/- 1.4 microM for I, 26 +/- 1.1 microM for II and 10 +/- 0.7 microM for IIa. These biflavonoids were assayed against human K562 leukemia cells in 45-h culture, but only I showed 42% growth inhibitory activity at 90 microM. Our results suggest that biflavonoids are targets for DNA topoisomerases and their cytotoxicity is dependent on tumor cell type.

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Topoisomerase inhibitors are agents with anticancer activity. 7"-O-Methyl-agathisflavone (I) and amentoflavone (II) are biflavonoids and were isolated from the Brazilian plants Ouratea hexasperma and O. semiserrata, respectively. These biflavonoids and the acetyl derivative of II (IIa) are inhibitors of human DNA topoisomerases I at 200 æM, as demonstrated by the relaxation assay of supercoiled DNA, and only agathisflavone (I) at 200 æM also inhibited DNA topoisomerases II-alpha, as observed by decatenation and relaxation assays. The biflavonoids showed concentration-dependent growth inhibitory activities on Ehrlich carcinoma cells in 45-h culture, assayed by a tetrazolium method, with IC50 = 24 ± 1.4 æM for I, 26 ± 1.1 æM for II and 10 ± 0.7 æM for IIa. These biflavonoids were assayed against human K562 leukemia cells in 45-h culture, but only I showed 42 percent growth inhibitory activity at 90 æM. Our results suggest that biflavonoids are targets for DNA topoisomerases and their cytotoxicity is dependent on tumor cell type

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