Results of surgical treatment of hepatic hydatidosis: Current therapeutic modifications

Hepatic hydatidosis is an endemic disease that affects vast segments of the populations of various countries in the Mediterranean region, South America, the Pacific, and temperate zone nations that possess large numbers of sheep. Four hundred and ten patients bearing 561 hydatid cysts were treated at 2 major hospitals in Madrid, Spain in the period 1974–1989. In order to establish the modifications in diagnostic and therapeutic management introduced as a result of modernization of our clinical facilities and improved technological standards, they were divided into 2 groups: group A corresponded to the period 1974–1984, and group B, corresponded to the period 1985–1989. Since no effective parasiticide agent is available, hepatic hydatidosis must be treated surgically. Today's better knowledge and advancements in liver surgery have made it possible to extirpate the cyst completely with little risk and improved results; hepatic resection should only be considered in exceptional cases; aspiration, drainage procedures, or partial resections of the cyst yield inferior results. We have had no relapse of the hydatid disease in the liver or in any other abdominal site.

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Resumen La hidatidosis hepática es una enfermedad endémica que afecta a vastos segmentas de las poblaciones de diversos países de la región mediterránea, Sur América, el Pacífico, y las naciones de las zonas templadas que mantienen grandes rebanos de ovejas. Cuatrocientos diez pacientes con 561 quistes hidatídicos fueron tratados en 2 grandes hospitales de Madrid, España en el período 1974–1989. Con el propósito de establecer las modificaciones en el manejo diagnóstico y terapéutico ocurridas como resultado de la modernización de nuestras facilidades clínicas y de superiores estándares tecnológicos, dividimos la población total de estos pacientes en 2 grandes grupos: grupo A, correspondiente al período 1974–1984, y grupo B, correspondiente al período 1985–1989. Puesto que no existe un agente parasitocida efectivo, la hidatidosis hepática debe ser tratada quirúrgicamente. El mejor conocimiento actual y el avance en la cirugía hepática han hecho posible la extirpatión completa del quiste con bajo riesgo y mejores resultados; la resection hepática debe ser considerada sólo en casos excepcionales; la aspiración, los procedimientos de drenaje o las resecciones parciales del quiste se asocian con malos resultados. En nuestra experiencia no hemos tenido recurrencia de la enfermedad ni en el hígado ni en otros órganos.

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Résumé Le kyste hydatique du foie est une maladie endémique qui touche une partie importante de la population dans différents pays de la région méditerranéenne, en Amérique du Sud, dans le Pacifique, et dans les pays de la zone tempérée qui ont beaucoup de moutons. Quatre cent dix patients porteurs de 561 kystes hydatiques ont été traités dans les deux plus grands hôpitaux de Madrid en Espagne de 1974 à 1989. Pour mesurer les progrès dans le diagnostic et le traitement dus à la modernisation de notre équipement médical et à une meilleure technologie, les patients ont été divisés en 2 groupes chronologiques: groupe A de 1974 à 1984 et groupe B de 1985 à 1989. Comme il n'y a pas actuellement de médicament efficace contre ce parasite, on doit traiter par la chirurgie le kyste hydatique. Aujourd'hui, les connaissances plus étendues et les progrès dans la chirurgie du foie permettent d'enlever complètement le kyste avec peu de risques et avec de meilleurs résultats; la résection du foie ne doit être envisagée que dans de rares cas. Les procédés d'aspiration ou de drainage ou les résections partielles du kyste donne des résultats moins bons. Nous n'avons pas eu de récidive du kyste hydatique, ni au foie ni dans une autre localisation péritonéale.

     

Gigantic diverticulum of the colon. A complication of diverticulosis?]

We present a patient affected of diverticular disease of the colon, with diverticulosis and two giant diverticula of the sigma, both located at the mesenteric edge. We would like to stress the low incidence of reports about this entity in the medical literature, its uncommon location and the fact of a double lesion coinciding in a single patient. We discuss the most important nosocomial aspects and the different diagnoses. Finally, we support the idea of distinguishing three different entities that in the medical literature are usually unified as a single "giant diverticulum of the colon". We reaffirm ourselves on the importance of an early diagnosis and a correct indication for surgery.     

Hepatitis G virus infection in hemodialysis patients and its relationship with hepatitis C virus infection

Our aim was to study the characteristics of hepatitis G virus (HGV) infection in hemodialysis (HD) patients. We evaluated 108 patients from two different units (A: 67 patients; B: 41 patients). HGV RNA and HCV RNA were detected by PCR. Nineteen patients (17.6%) were HGV RNA positive (20.9% in unit A and 12.2% in unit B (NS)). HCV RNA was positive in 19 patients (17.6%) (28.4% in unit A and 0 in unit B (p < 0.01)). Eight patients were HGV RNA and HCV RNA positive (group I), 11 HGV RNA positive (group II), 11 HCV RNA positive (group III), and 78 negative for both viruses (group IV). Time on HD was 51.3 +/- 37.0 months for group I, 36.0 +/- 27.9 months for group II, 63.5 +/- 40.2 months for group III, and 26.4 +/- 27.1 months for group IV (p < 0.01 for I and III). Seven patients (87.5%) from group I, 9 (81.8%) from group II, 10 (90.9%) from group III, and 44 (56.4%) from group IV had a history of transfusion (p < 0.03 for I, II and III). Two patients (25%) from group I, none from group II, 5 (45.4%) from group III, and 6 (7.7%) from group IV had chronic ALAT elevation (p < 0.01 for I and III). We conclude that HGV infection was frequent in our HD patients, related to transfusions and independent of HCV prevalence, and that HGV infection itself was not a cause of ALAT elevation suggesting chronic hepatitis.     

Pharmacodynamic evaluation of the epidermal growth factor receptor inhibitor OSI-774 in human epidermis of cancer patients.

BACKGROUND: OSI-774 is an inhibitor of the epidermal growth factor receptor tyrosine kinase (EGFR-TK) currently in clinical development. In preclinical models, the antitumor activity of OSI-774 was directly related to its ability to inhibit the EGFR-TK. On the basis of these data, we hypothesized that inhibition of the EGFR-TK will be required for this agent to be effective in the clinic. This study evaluated the pharmacodynamic effects of OSI-774 in normal skin tissues collected from patients treated with the agent in a Phase I study. METHODS: Patients with advanced cancer who were treated in a Phase I study of OSI-774 underwent a biopsy of normal skin epidermis at baseline and after the last dose of drug in the first course of treatment. The expression and activation of the EGFR, downstream signaling extracytoplasmatic-regulated kinase (Erk), and cell cycle regulator p27 were determined in paraffin-embedded skin tissues using an immunohistochemical method (IHC). The IHC data were analyzed using both a semiquantitative scoring system and an automatic absorbance quantitative IHC method. The number of cells with nuclear staining of p27 per 500 cells was determined. Plasma samples were collected to quantitate OSI-774 plasma concentrations. RESULTS: A total of 56 skin specimens was collected from 28 patients treated with OSI-774 at doses ranging from 25 to 200 mg/day. There was a significant decrease in phospho-EGFR (Tyr 1173) expression as determined semiquantitatively with OSI-774 treatment [2.75 +/- 0.51 (mean +/- SD) pretreatment versus 2.36 +/- 0.76 after treatment, pair comparison P = 0.01]. The quantitative ratio [(phopho-EGFR/EGFR) x 100] of phospho-EGFR (Tyr1173) decreased from 64.16 +/- 36.58 pretreatment to 48.87 +/- 35.37 post-treatment (pair comparison, P = 0.02). No significant differences were observed in phospho-Erk (Thr202/Tyr204) expression. The mean number of cells with nuclear staining for p27 increased from 185 +/- 101 (mean +/- SD) pretreatment to 253 +/- 111 post-treatment (pair comparison P = 0.02). A total of 12 (42.8%), 7 (25%), and 14 (50%) patients had >25% variation in the ratio of phospho-EGFR (Tyr1173), phospho-Erk (Thr202/Tyr204), and p27 expression, respectively. Only changes in p27 expression were related to the administered dose of OSI-774. CONCLUSIONS: OSI-774 exerted pharmacodynamic effects in skin tissues of 30-50% of patients treated with the agent. Up-regulation of p27, which is a downstream effect of EGFR inhibition, was dose related. Although there was a significant decrement in phospho-EGFR (Tyr1173), it was not related to the administered dose of OSI-774. On the basis of these findings and the relatively simple and reliable method to measure p27 expression, this biomarker appears to be the most promising and is being evaluated in Phase II studies as a predictor of clinical outcome.     

Pharmacodynamic Evaluation of CCI-779, an Inhibitor of mTOR, in Cancer Patients.

CCI-779 is an ester of rapamycin and inhibitor of mammalian target of rapamycin (mTOR) currently in Phase II clinical development for the treatment of patients with cancer. CCI-779 interacts with mTOR and inhibits its kinase activity, resulting in inhibition of the mTOR-regulated translational controllers p70(s6) kinase and 4E-BP1. Ultimately, CCI-779 decreases the translation of mRNAs involved in the control of the cell cycle, resulting in cell cycle arrest. The objective of this study was to develop a method to determine the pharmacodynamic effects of CCI-779 suitable for use in clinical trials. Exposure of Raji lymphoblastoid cells to increasing concentrations of rapamycin resulted in a linear concentration-dependent inhibition of p70(s6) kinase activity, suggesting that p70(s6) kinase activity could be an appropriate marker for mTOR-interacting agents. In subsequent experiments, treatment of nude mice bearing the CCI-779 susceptible breast cancer cell line MDA-468 with a single dose of 10 mg/kg CCI-779 resulted in a >80% inhibition of p70(s6) kinase activity in peripheral blood mononuclear cells (PBMCs) 72 h after treatment. Importantly, the degree of p70(s6) kinase inhibition was identical in PBMCs and simultaneously collected tumor tissue, suggesting that the PBMCs are an adequate surrogate tissue for p70(s6) kinase activity in vivo. The intrasubject coefficient of variation of p70(s6) kinase activity measured in PBMCs collected from five healthy volunteers on days 1, 4, and 8 was 14%, indicating that p70(s6) kinase activity in PBMCs remains relatively stable over time. Finally, p70(s6) kinase activity was measured in PBMCs from nine patients with renal cell cancer treated with a single dose of 25, 75, or 250 mg of CCI-779 i.v. (three patients each). PBMCs were collected on days 2, 4, and 8 after CCI-779 treatment. In this small data set, eight of the nine patients had evidence of p70(s6) kinase activity inhibition after treatment that was independent of the administered dose. There was a significant linear association between time to disease progression and inhibition of p70(s6) kinase activity 24 h after treatment. In conclusion, these results indicate that the pharmacodynamic effects of CCI-779 can be determined using a p70(s6) kinase assay in PBMCs. This assay is currently being incorporated in Phase I and II studies with CCI-779 to determine its relationship with dose and plasma concentration of the agent and its value as a predictor of treatment efficacy.     

The metabolic syndrome among postmenopausal women in Ecuador.

BACKGROUND: The prevalence of the metabolic syndrome increases with age and after the onset of menopause, and may explain in part the apparent acceleration of cardiovascular disease in postmenopausal women. OBJECTIVE: To determine the prevalence of metabolic syndrome and related risk determinants among postmenopausal women in Ecuador. METHODS: Postmenopausal women >or=40 years of age, non-users of hormone therapy and with an intact uterus, were asked to participate in a metabolic syndrome screening and educational program at the Institute of Biomedicine of the Universidad Católica of Guayaquil, Ecuador. Sociodemographic data, waist circumference and blood pressure measurements were recorded, and a fasting blood sample obtained for serum glucose and lipid profile determinations. Woman were counseled and managed according to the results. Metabolic syndrome was defined in accordance with the criteria of the Third Adult Treatment Panel (ATP III). RESULTS: Three hundred and twenty-five postmenopausal women entered the program. Mean (+/-standard deviation) age was 55.9 +/- 8.1 years, 53.5% of them were aged >or=54 years (median). The prevalence of metabolic syndrome, according to ATP III criteria, was 41.5%. Using the same criteria, 38.8%, 16.6%, 56.9% and 54.2% of the women presented with hypertension, diabetes, hypertriglyceridemia and abdominal obesity, respectively. More than 40% of women determined to have hypertension or diabetes lacked knowing so. Logistic regression analysis determined that age increased the risk of presenting hypertension and diabetes (odds ratio (95% confidence interval): 2.0 (1.2-3.2) and 1.6 (0.9-3.0), respectively, p < 0.05), entities which in turn duplicated the risk of having high triglyceride levels. Sedentary women with <5 years since menopause onset were at higher risk of having abdominal obesity, which was directly related to diabetes and hypertension. CONCLUSIONS: In this postmenopausal Ecuadorian population the prevalence of the metabolic syndrome was high and its determinant factors related to age, time since menopause onset and sedentary habits. Because of the implications for cardiovascular risk, counseling programs directed toward high-risk populations should be encouraged.