Extracellular volume measured by whole body CT scans predicts chronic cardiotoxicity in breast cancer patients treated with neoadjuvant therapies based on anthracyclines: A retrospective study.

INTRODUCTION: Neoadjuvant chemotherapies for breast cancer (BC) are effective but potentially cardiotoxic, and expose long survivors at risk of chemotherapy-related cardiac dysfunction (CTRCD). Unfortunately, early screening for CTRCD has actual diagnostic limits. Myocardial extracellular volume (mECV) is a radiological marker used in cardiac CT scans and cardiac magnetic resonance for diagnosis and follow-up of CTRCD. It can be measured in whole-body CT (WB-CT) scan, routinely performed in patients at high risk of relapse, to evaluate CTRCD occurrence during oncological follow-up. METHODS: 82 WB-CT scans were examined at baseline (T0) and during oncological follow-up at first year (T1) and fifth year (T5) after the end of neoadjuvant treatment. mECV was measured at 1 min (PP) and 5 min (DP) after contrast injection. 31 echocardiograms were retrieved in T1 to perform a linear correlation between mECV and left ventricular ejection fraction (LVEF). RESULTS: mECV values in T0 were similar between the two groups both in PP and in DP. Significant results were found for PP values in T1 (37.0 % vs 32 %, p = 0.0005) and in T5 (27.2 % vs 31.2 %, p = 0.025). A cut-off value of 35 % in PP proved significant in T1 (OR = 12.4, p = 0.004), while mECV was inversely correlated with LVEF both in PP (adj-S = -3.54, adj-p = 0.002) and in DP (adj-S = -2.51, adj-p = 0.0002), suggesting a synergistic action with the age at diagnosis (p < 0.0001, respectively). CONCLUSIONS: WB-CT scans performed during oncological reassessment in patients at high-risk of recurrence could be used for CTRCD screening in cardiovascular low-risk patients, especially in aging patients with mECV values above 35 %.

Intoxicación experimental con Nierembergia linariifolia var. linariifolia en cabras

Nierembergia linariifolia var. linariifolia ha sido sospechada históricamente como planta tóxica en algunas regiones del noroeste de Argentina. Se administró una dosis de 10 g de materia seca de planta molida/kg de peso, a tres cabras adultas mediante el empleo de sonda nasogástrica. Otros tres animales permanecieron como grupo control y recibieron heno de alfalfa. Las cabras que recibieron la planta, presentaron signos clínicos de cólico abdominal entre las 7 y 45 horas post-administración. Ninguno de los animales murió y todos se recuperaron totalmente a las 72 horas de iniciado el ensayo. Nierembergia linariifolia var. linariaefolia demostró tener efectos tóxicos a nivel gastrointestinal a la dosis administrada, aunque no se observaron daños más severos.

The species Nierembergia linariifolia var. linariifolia has been historically incriminated as toxic for animals in northwestern Argentina. A dose of 10 g of ground dry matter / kg of live weight was administered to three adult goats by the use of a nasogastric tube. Another three animals remained as "control group", and receiving alfalfa hay. The goats that received the plant presented clinical signs of abdominal colic between 7 and 45 hours post-administration. None of the animals died and all recovered fully within 72 hours of initiation of the test. Nierembergia linariifolia var. linariaefolia showed to have toxic effects at the gastrointestinal level at the dose administered, although no severe damage was observed.

Cultural adaptation and linguistic validation of the Family Decision Making Self Efficacy Scale (FDMSES).

INTRODUCTION: Nurses, following their ethical mandate, collaborate with other health and social professionals or people involved in caring activities. Caregivers in this context are becoming more and more significant for the family or the cared person, who for their stable presence and emotional proximity play a pivotal caring role. To maximize the contribution of caregivers, objective tools that emphasize their skill sets are necessary. The cross-cultural adaptation and validation of the Family Decision Making Self-Efficacy Scale is part of a larger project aimed at understanding the resilience of caregivers in the field of palliative care. Self-efficacy is one of the aspects of personality most closely associated with resilience. Self-efficacy is shown in a specific context, therefore, its study and evaluation of its level, require capabilities that enable individuals perceive themselves as effective in a particular circumstance. The Family Decision Making Self- Efficacy Scale assesses the behavior of caregivers of patients at the end of their life. METHODS: The Family Decision Making Self-Efficacy Scale was translated (forward and back translation) and was adapted to the Italian clinical cultural setting by a research team that included experts in palliative care, native translators with experience in nursing and experts in nursing. A consensus on the wording of each item in relation to semantic, idiomatic, experiential and conceptual equivalence was sought. The clarity of the wording and the pertinence of the items of the scenario with the conscious patient and with the unconscious patient were evaluated by a group of caregivers who tested the instrument. RESULTS: The Italian version of the instrument included 12 items for the scenario with the conscious patient and 12 for the scenario with the unconscious patient. The working group expressed consensus on the pretesting version of the instrument. The pre-testing version of the scale was tested on 60 caregivers, 47 taking care of conscious patients and 13 taking care of unconscious patients. In both cases the content of the items was judged relevant and understandable. CONCLUSIONS: The results for the cross-cultural validation were satisfactory and allowed the application of the instrument in the Italian context.

Somatostatin analogs therapy in gastroenteropancreatic neuroendocrine tumors: current aspects and new perspectives.

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare tumors that present many clinical features secreting peptides and neuroamines that cause distinct clinical syndromes such as carcinoid syndrome. However most of them are clinically silent until late presentation with mass effects. Surgical resection is the first line treatment for a patient with a GEP-NET while in metastatic disease multiple therapeutic approaches are possible. GEP-NETs are able to express somatostatin receptors (SSTRs) bounded by somatostatin (SST) or its synthetic analogs, although the subtypes and number of SSTRs expressed are very variable. In particular, SST analogs are used frequently to control hormone-related symptoms while their anti-neoplastic activity seems to result prevalently in tumor stabilization. Patients who fail to respond or cease to respond to standard SST analogs treatment seem to have a response to higher doses of these drugs. For this reason, the use of higher doses of SST analogs will probably improve the clinical management of these patients.

Medullary thyroid cancer: a promising model for targeted therapy.

In recent years, the clinical validation of molecular targeted therapies inhibiting the action of pathogenic tyrosine kinase (TK) has been one of the most exciting developments in cancer research. In this context, medullary thyroid carcinoma (MTC) represents a promising model. It is well known that in MTC, the RET receptor TK and its signal transduction pathways, lead to subsequent neoplastic transformation. Several strategies aimed at blocking the activation and signaling of RET have been preclinically tested. The most advanced results have been obtained by competitive inhibition of RET-TK activity by tyrosine kinases inhibitors (TKI). However, although the inhibition of the RET pathway is actually one of the most studied for therapeutic purposes, other signal transduction pathways have been recognized to contribute to the growth and functional activity of MTC and are considered attractive therapeutic targets. To date, surgery represents the only curative treatment of MTC. Despite promising initial results, studies on targeted agents are in early stages and several issues regarding preclinical evaluations and clinical trials of new targeted agents in MTC are still unresolved. Now, available mouse models bearing mutations of RET or other genes, which spontaneously develop MTC, promise to improve preclinical evaluation of activity of targeted compounds. Furthermore, the rarity of the disease and the number of patients available for enrollment may lessen the relevance of clinical trials. A major effort needs to be made by endocrinologists and oncologists to refer their patients for multi-institutional trials in order to optimize them, perform translational studies and expedite the availability of novel beneficial selective therapies.

[Preoperative nutritional status and surgical risk. Identification of promissory biochemical markers]. / Estado nutricional preoperatorio y riesgo quirúrgico. Identificación de marcadores bioquímicos promisorios.

BACKGROUND: The fact that deficient or even marginal nutritional levels may contribute to increase morbidity and mortality in the surgical patient is well accepted. The usefulness of vitamin and mineral markers has not been much explored. OBJECTIVE: To evaluate the usefulness of vitamin and mineral indicators as nutritional markers of surgical risk. METHODS: Biomarkers of vitamin A (plasma retinol), carotenes (plasma carotenes), vitamin C (plasma vitamin C), iron (hematocrit, hemoglobin, serum iron, transferrin saturation and erythrocyte protoporphyrin), calcium (calcium/creatinine in basal urine) and zinc (zinc/creatinine in basal urine), were performed 24 ours before surgery. Appearance of complications was evaluated in 100 adult patients from programmed surgical procedures of hernia (n = 41) or gallbladder lithiasis (n = 59), two of the most frequent interventions in general surgery services. RESULTS: Patients were grouped in those that presented postoperative complications (C; n = 26) and those who did not (NC; n=74). Two of the studied markers presented significant differences between both groups: plasma retinol and erythrocyte protoporphyrin. Plasma retinol of C was significantly lower than that obtained in NC: 33.2 +/- 13.5 microg/dl vs. 40.2 +/- 16.3 microg/dl; P = 0.0495 and an association between values below 30 microg/dl and postoperative complications was founded (53.8% in C vs. 30.1% in NC; P = 0.0360). Erythrocyte protoporphyrin of C was significantly higher to that obtained in NC: 52.0 +/- 34.0 microg/dl RBC vs. 36.8 +/- 17.5 microg/dl RBC; P = 0.0453 and the association between values higher than 70 microg/dl RBC and presence of complications were highly significant (25.0% vs. 4.2%; P = 0.0069). CONCLUSIONS: On the basis of the obtained results is concluded that plasma retinol and erythrocyte protoporphyrin would provide useful tools in evaluating surgical risk since they had been allowed to identify patients who were at risk of suffering postoperative complications.

Estado nutricional preoperatorio y riesgo quirúrgico. Identificación de marcadores bioquímicos promisorios / Preoperative nutritional status and surgical risk. Identification of promissory biochemical markers

Introducción: Existe una acumulación de evidencias de que niveles de nutrición deficientes o aún marginales pueden contribuir al aumento de morbilidad y mortalidad en el paciente quirúrgico. La utilidad de marcadores de vitaminas y minerales ha sido poco explorada. Objetivo: Evaluar la utilidad de indicadores de vitaminas y minerales como marcadores de riesgo quirúrgico. Métodos: Se estudió la asociación entre marcadores de vitamina A (retinol plasmático), carotenos (carotenos plasmáticos), vitamina C (vitamina C plasmática), hierro (hematocrito, hemoglobina, hierro sérico, saturación de transferrina y protoporfirina eritrocitaria), calcio (calcio/creatinina en orina basal) y zinc (zinc/creatinina en orina basal), realizados dentro de las 24 horas previas a la cirugía, y la aparición de complicaciones postoperatorias en 100 pacientes adultos sometidos a intervenciones por hernia (n = 41) o litiasis vesicular (n = 59), dos intervenciones muy frecuentes en los servicios de cirugía general. Resultados: Los pacientes se dividieron en aquellos que presentaron complicaciones postoperatorias (C; n = 26) y aquellos que evolucionaron sin complicaciones (NC; n = 74). Dos de los marcadores estudiados fueron los que presentaron las mayores diferencias entre ambos grupos: retinol plasmático y protoporfirina eritrocitaria. El retinol plasmático del grupo C fue significativamente menor al del grupo NC: 33,2 ± 13,5 μg/dl vs 40,2 ± 16,3 μg/dl; P = 0,0495 y se halló asociación significativa entre valores inferiores a 30 μg/dl y aparición de complicaciones (53,8% en C vs 30,1% en NC; P = 0,0360). La protoporfirina eritrocitaria del grupo C fue significativamente mayor a la del grupo NC: 52,0 ± 34,0 vs 36,8 ± 17,5 μg/dl g.r; P = 0,0453 y la asociación entre valores superiores a 70 μg/dl g.r. y presencia de complicaciones fue altamente significativa (25,0% vs 4,2%; P = 0,0069). Conclusiones: Dos indicadores de micronutrientes: retinol plasmático y protoporfirina eritrocitaria, resultaron marcadores promisorios de riesgo quirúrgico por haber permitido identificar pacientes en riesgo de sufrir complicaciones postoperatorias (AU)

Background: The fact that deficient or even marginal nutritional levels may contribute to increase morbidity and mortality in the surgical patient is well accepted. The usefulness of vitamin and mineral markers has not been much explored. Objective: To evaluate the usefulness of vitamin and mineral indicators as nutritional markers of surgical risk. Methods: Biomarkers of vitamin A (plasma retinol), carotenes (plasma carotenes), vitamin C (plasma vitamin C), iron (hematocrit, hemoglobin, serum iron, transferrin saturation and erythrocyte protoporphyrin), calcium (calcium/creatinine in basal urine) and zinc (zinc/creatinine in basal urine), were performed 24 ours before surgery. Appearance of complications was evaluated in 100 adult patients from programmed surgical procedures of hernia (n = 41) or gallbladder lithiasis (n = 59), two of the most frequent interventions in general surgery services. Results: Patients were grouped in those that presented postoperative complications (C; n = 26) and those who did not (NC; n=74). Two of the studied markers presented significant differences between both groups: plasma retinol and erythrocyte protoporphyrin. Plasma retinol of C was significantly lower than that obtained in NC: 33.2 ± 13.5 μg/dl vs. 40.2 ± 16.3 μg/dl; P = 0.0495 and an association between values below 30 μg/dl and postoperative complications was founded (53.8% in C vs. 30.1% in NC; P = 0.0360). Erythrocyte protoporphyrin of C was significantly higher to that obtained in NC: 52.0 ± 34.0 μg/dl RBC vs. 36.8 ± 17.5 μg/dl RBC; P = 0.0453 and the association between values higher than 70 μg/dl RBC and presence of complications were highly significant (25.0% vs. 4.2%; P = 0.0069). Conclusions: On the basis of the obtained results is concluded that plasma retinol and erythrocyte protoporphyrin would provide useful tools in evaluating surgical risk since they had been allowed to identify patients who were at risk of suffering postoperative complications (AU)

Chemoprevention in gastrointestinal adenocarcinoma: for few but not for all?

Despite the general progress of the last two decades in oncogenesis mechanism comprehension, in screening and surveillance programs, in technological support to diagnosis and in treatment protocols, the long-term survival of gastrointestinal (GI) cancer patients is not substantially changed. Therefore chemoprevention strategies still appear as a possible alternative to screening and surveillance programs in reducing the incidence and the mortality for GI cancer, at an acceptable cost/effectiveness ratio. The present review is focused on three GI cancers: esophageal adenocarcinoma, gastric cancer and colorectal cancer and their respective precarcinogenic lesions. The authors examine, for each neoplasia, the available chemopreventive agents, their mechanism of action in preventing cancer, the potential targets in the cell growth process, the cost/effectiveness ratio and, whenever present in literature, a comparison with other cancer prevention strategies. The authors conclude that, at present, with the available agents, chemoprevention is not indicated for all patients at low or moderate risk for GI cancer, and should not be considered as a substitute for endoscopic surveillance. In high-risk patients only, both chemoprevention and surveillance could be used. In future more specific agents and combined therapies should be tested in specific group of patients identified by their genomic susceptibility to develop cancer and responsiveness to therapy.

Focus on Fotemustine.

Fotemustine is a cytotoxic alkylating agent, belonging to the group of nitrosourea family. Its mechanism of action is similar to that of other nitrosoureas, characterized by a mono-functional/bi-functional alkylating activity. Worth of consideration is the finding that the presence of high levels of the DNA repair enzyme O6-methylguanine-DNA-methyltransferase (MGMT) in cancer cells confers drug resistance. In different clinical trials Fotemustine showed a remarkable antitumor activity as single agent, and in association with other antineoplastic compounds or treatment modalities. Moreover, its toxicity is generally considered acceptable. The drug has been employed in the treatment of metastatic melanoma, and, on the basis of its pharmacokinetic properties, in brain tumors, either primitive or metastatic. Moreover, Fotemustine shows pharmacodynamic properties similar to those of mono-functional alkylating compounds (e.g. DNA methylating drugs, such as Temozolomide), that have been recently considered for the management of acute refractory leukaemia. Therefore, it is reasonable to assume that this agent could be a good candidate to play a potential role in haematological malignancies.

Therapy of breast cancer with molecular targeting agents.

Invasive breast cancer is a heterogeneous disease sustained by intercorrelated and complex growth pathways. Classically, human breast carcinoma has been classified for therapeutic purposes in two distinct categories: one hormone-correlated, the other hormone-uncorrelated. However, the recent advancements of the technology applied to molecular biology by genomic and proteomic analyses have suggested that many more factors are involved in breast cancer growth and progression and that some clusters of these distinguish subgroups of patients at different prognosis. The knowledge of the diversities between tumor and normal tissue of origin is the key to identify novel targets for new selective therapeutic strategies. In fact, the principal goal of molecular-targeted therapy is the suppression of the transformed phenotype minimally affecting normal cells. This review focuses on the molecular targeting compounds directed against the known molecular pathways involved in breast cancer such as: type I growth factors (HER-2/neu; epidermal growth factor receptor [EGFR]), angiogenesis, cyclooxigenase-2 (COX-2) and farnesylation. Presently, trastuzumab is the first agent approved for therapy of HER-2/neu overexpressing tumors. Several other compounds directed against different targets have entered clinical evaluation and the preliminary results are here presented and commented. The major challenges on the clinical development of targeted therapy include the proper selection of patients, the identification of the optimal dosage and schedule of administration, the combinations with conventional treatments and the more appropriate therapeutic strategy.

A novel method for monitoring response to chemotherapy based on the detection of circulating cancer cells: a case report.

We describe a novel method for detecting micrometastasis in the blood stream of cancer patients based on RT-PCR amplification of tumor-associated carcinoembryonic antigen (CEA) mRNA. To increase sensitivity and specificity of RT-PCR, CEA transcript was selectively up-regulated in cancer cells by exposure of peripheral blood to non-toxic concentrations of staurosporine (ST). Thereafter, polyA(+) RNA was extracted from tumor cells captured by means of magnetic beads coated with a monoclonal antibody against a common human epithelial antigen. Finally, RNA was subjected to RT-PCR analysis of CEA transcript. Using this approach, we demonstrated an ST-mediated increase in CEA transcript in blood specimens collected from a patient with metastatic colon cancer before receiving treatment with 5-fluorouracil/leucovorin. After a few cycles of chemotherapy, CEA-positive tumor cells were no longer detected. Clinical follow-up of this patient indicated that treatment with chemotherapy induced a dramatic reduction in liver metastasis. Therefore, it can be hypothesized that lack of CEA transcript detection might be consistent with disappearance or at least marked reduction of circulating tumor cells.

[Nutritional status of surgical patients without apparent nutritional compromise]. / Estado nutricional de pacientes quirúrgicos sin aparente compromiso nutricional.

Nutritional status of 80 preoperative patients from programmed surgeries of hernias and lithiasis was studied by anthropometric and biochemical parameters. Nutritional deficiencies related to pathology were not expected in these patients. Results were as follows: 77% of the population showed overweight, being 15% obese. Prevalent protein intake, evaluated by the urea nitrogen/creatinine ratio, was adequate in 87.5% of the patients; however, patients presented 72% of albumin, 52% of prealbumin and 50% of RBP below reference values. Transferrin, ceruloplasmin, alpha 2-macroglobulin and haptoglobin were not decreased. Assessment of vitamin A, carotenes and vitamin C showed plasmatic levels below reference values in 16% of the patients for vitamin A, 5% for carotenes and 27% for vitamin C. Respect to calcium status, data of calcium/creatinine ratio show deficiency in 45% of the population. Respect to iron, the nutritional status was in general adequate, patients at risk being 5% by Htc, 11% by Hb, 5% by TS% and 12.5% by FEP, women showed over twice abnormal values than men. Although some isolated relations were observed, in this population sex, age and pathology were variable that did not affect in a relevant way the nutritional status. In spite of the individual analysis of each nutrient did not show important deficiencies, the analysis by patient showed that only a few of them (7%) presented an optimal biochemical profile with all the studied parameters within the reference values.

Unusual reaction to chlorambucil: a case report.

In this brief report we describe a case of cutaneous reaction during treatment of chronic lymphatic leukemia (CLL) with chlorambucil. The patient developed a confluent maculopapular erythema and large flaccid bullae of trunk, legs, feet and mucous membranes, with fever up to 38 degrees C. Toxic epidermal necrolisis (TEN) was supposed and the diagnosis was confirmed by a skin patch test followed by cutaneous biopsy. TEN by chlorambucil is a rare syndrome that may be considered in presence of cutaneous reaction to this drug.

Pancreatic duct occlusion in the management of acute necrotizing pancreatitis in a canine model.

Based on results reported by others in using prolamine (Ethibloc; Ethicon Gmb H) to treat patients with chronic pancreatitis, without any observed pancreatic complications, we decided to use pancreatic duct occlusion experimentally in dogs in which we induced acute pancreatitis by the injection of calcium chloride into the pancreatic duct. This injection proved to be 100% lethal in the 5 animals constituting the control group, none of which were treated after the injection. Acute pancreatitis was then induced in 57 animals, also by injection of calcium chloride. These dogs were then treated with one of three substances that share the same physical properties: prolamine; Tissucol (Immuno AG, Vienna), a biologic tissue adhesive; silicone (Xantopren, Bayer Dental D-5090 Leverkusen). Thirty-seven dogs were treated with prolamine, 10 dogs with Tissucol, and 10 with silicone. The mortality rate in the 57 treated animals was 12.2%, compared to the 100% rate in the untreated control group. The mechanical action achieved by blocking the pancreatic duct shows how the evolution of acute pancreatitis at different stages could be modified. This specific treatment limits the pathophysiologic process of acute pancreatitis in dogs. These findings provide us with a promising outlook for the treatment of this severe illness.

[Experimental acute necrotico-hemorrhagic pancreatitis in dogs. Treatment by intraductal block]. / Pancréatite aiguë nécrotico-hémorragique expérimentale chez le chien. Traitement par blocage intra-canalaire.

The aim of this experimental study was to demonstrate that the mortality of calcium chlorine induced acute pancreatitis in the dog was decreased by the intraductal injection of solid substances. Seventy-two dogs were used. In the control group (n = 5) the mortality was 100%. Three different drugs were used for the intraductal injection: Ethibloc (n = 37), Tissucol (n = 10) and silicones (n = 10). The mortality rate has been respectively of 13.5, 10 and 10%. In order to define at which level of the pancreatic duct the obstruction had a maximum efficiency, 10 dogs underwent a distal ligation of the pancreatic duct after induction of the pancreatitis. The mortality rate in this group was 100%. It can be therefore concluded that only the complete obstruction of the pancreatic duct decreases the mortality rate in this experimental model.

Primeras observaciones sobre la aplicacion de la prolamina en la pancreatitis aguda necrohemorragica en el hombre. / First observations about the use of prolamine in acute necrohemorrhagic pancreatitis in the man

Continuando una serie de estudios experimentales se presentan las 2 primeras observaciones en el ser humano, de pancreatitis aguda grave tratadas mediante bloqueo intraductal pancreatico con prolamina; existian lesiones hemorragicas severas. Se efectuo ademas colecistectomia, drenaje del coledoco, duodenotomia y papiloesfinterectomia. Ambas enfermas evolucionaron bien, aunque una de ellas con una fistula pancreatica y un absceso subhepatico que curaron espontaneamente. Se evalua la posibilidad de emplear esta droga indicando la intervencion precoz. Se sugiere la posibilidad de combinar el tratamiento quirurgico con el endoscopico para la aplicacion de la droga sin necesidad de hacerlo por via transduodenopapilar

Suturas manuales y mecanicas en cirugia colonica. Estudio experimental comparativo. / Manual and mechanic sutures in colon surgery. Experimental comparative study

Con el objeto de estudiar los resultados histopatologicos comparativos en cirugia colonica utilizando suturas manuales y mecanicas fueron operados 18 perros. Se evaluaron las caracteristicas macro y microscopicas de ambas suturas, hallandose diferencias significativas en los procesos de necrosis y neoformacion

Primeras observaciones sobre la aplicacion de la prolamina en la pancreatitis aguda necrohemorragica en el hombre. / First observations about the use of prolamine in acute necrohemorrhagic pancreatitis in the man

Continuando una serie de estudios experimentales se presentan las 2 primeras observaciones en el ser humano, de pancreatitis aguda grave tratadas mediante bloqueo intraductal pancreatico con prolamina; existian lesiones hemorragicas severas. Se efectuo ademas colecistectomia, drenaje del coledoco, duodenotomia y papiloesfinterectomia. Ambas enfermas evolucionaron bien, aunque una de ellas con una fistula pancreatica y un absceso subhepatico que curaron espontaneamente. Se evalua la posibilidad de emplear esta droga indicando la intervencion precoz. Se sugiere la posibilidad de combinar el tratamiento quirurgico con el endoscopico para la aplicacion de la droga sin necesidad de hacerlo por via transduodenopapilar