Liver radiologic findings of chemotherapy-induced toxicity in liver colorectal metastases patients.

There are a number of chemotherapy-effects that should be assessed with liver imaging since they have an influence on surgical morbidity. Chemotherapy-related complications, steatosis, chemotherapy-associated steatohepatitis (CASH), and SOS might impair the hepatic parenchyma, thus reducing the functionality and influencing the outcome following resection. The main role of a radiologist is to provide an accurate diagnosis of the lesion. With constant advances in medicine, a radiologist's role should extend beyond just reporting the data of tumor, providing additional information that may greatly improve patient care. Radiologists should assess both chemotherapy effects on the hepatic metastasis itself, as well as chemo-induced focal and diffuse modifications of non-tumor hepatic parenchyma, since it is important to avoid impaired hepatic function after hepatic resection.

Validation of a proliferation-based expression signature as prognostic marker in early stage lung adenocarcinoma.

PURPOSE: New prognostic markers to guide treatment decisions in early stage non-small cell lung cancer are necessary to improve patient outcomes. In this report, we assess the utility of a predefined mRNA expression signature of cell-cycle progression genes (CCP score) to define 5-year risk of lung cancer-related death in patients with early stage lung adenocarcinoma. EXPERIMENTAL DESIGN: A CCP score was calculated from the mRNA expression levels of 31 proliferation genes in stage I and stage II tumor samples from two public microarray datasets [Director's Consortium (DC) and GSE31210]. The same gene set was tested by quantitative PCR in 381 formalin-fixed paraffin-embedded (FFPE) primary tumors. Association of the CCP score with outcome was assessed by Cox proportional hazards analysis. RESULTS: In univariate analysis, the CCP score was a strong predictor of cancer-specific survival in both the Director's Consortium cohort (P = 0.00014; HR = 2.08; 95% CI, 1.43-3.02) and GSE31210 (P = 0.0010; HR = 2.25; 95% CI, 1.42-3.56). In multivariate analysis, the CCP score remained the dominant prognostic marker in the presence of clinical variables (P = 0.0022; HR = 2.02; 95% CI, 1.29-3.17 in Director's Consortium, P = 0.0026; HR = 2.16; 95% CI, 1.32-3.53 in GSE31210). On a quantitative PCR platform, the CCP score maintained highly significant prognostic value in FFPE-derived mRNA from clinical samples in both univariate (P = 0.00033; HR = 2.10; 95% CI, 1.39-3.17) and multivariate analyses (P = 0.0071; HR = 1.92; 95% CI, 1.18-3.10). CONCLUSIONS: The CCP score is a significant predictor of lung cancer death in early stage lung adenocarcinoma treated with surgery and may be a valuable tool in selecting patients for adjuvant treatment.

Histologic patterns and molecular characteristics of lung adenocarcinoma associated with clinical outcome.

BACKGROUND: Lung adenocarcinoma is histologically heterogeneous and has 5 distinct histologic growth patterns: lepidic, acinar, papillary, micropapillary, and solid. To date, there is no consensus regarding the clinical utility of these patterns. METHODS: The authors performed a detailed semiquantitative assessment of histologic patterns of 240 lung adenocarcinomas and determined the association with patients' clinicopathologic features, including recurrence-free survival (RFS) and overall survival (OS) rates. In a subset of tumors, expression levels of 2 prognostic molecular markers were evaluated: thyroid transcription factor-1 (TTF-1) (n = 218) and a panel of 5 proteins (referred as the FILM signature index) (n = 185). RESULTS: Four mutually exclusive tumor histology pattern groups were identified: 1) any solid (38%), 2) any papillary but no solid (14%), 3) lepidic and acinar but no solid or papillary (30%), and 4) acinar only (18%). Patients in group 3 had a higher RFS rate than patients in group 1 (hazard ratio [HR], 0.4510; P = .0165) and group 2 (HR, 0.4253; P = .0425). Solid pattern tumors (group 1) were associated with a lower OS rate than nonsolid pattern tumors (all stages: HR; 1.665; P = .0144; stages I and II: HR, 2.157; P = .008). In the patients who had tumors with a nonsolid pattern, high TTF-1 expression was associated significantly with higher RFS (HR, 0.994; P = .0017) and OS (HR, 0.996; P = .0276) rates in all stages, and a high FILM signature index score was associated with lower RFS and OS rates in all stages (RFS: HR, 1.343; P = .0192; OS: HR, 1.371; P = .0156) and in stages I and II (RFS: HR, 1.419; P = .0095; OS: HR, 1.315; P = .0422). CONCLUSIONS: The presence of a solid histologic pattern was identified as a marker of unfavorable prognosis in patients with primary lung adenocarcinoma. High TTF-1 expression and low FILM signature index scores were associated with a better prognosis for patients who had tumors with a nonsolid pattern.

Source and clinical motivation of orders for contrast-enhanced sonography (CEUS) of the liver: A prospective single-center survey.

Contrast-enhanced sonography (CEUS) has become a routine part of diagnostic imaging of the liver. Its possibilities, limitations, and indications have been defined in adequately large clinical series and in guidelines and recommendations. We prospectively evaluated physicians' orders for hepatic CEUS received in the radiology department of a large oncology center in Naples, Italy from May 2009 to April 2010. Radiologists performing the CEUS examinations filled out a form that included patient demography, source and type of patient referral, and clinical indications for the examination. During the study period, 564 patients aged 17-86 years (mean, 58 years) were referred to our department for CEUS liver studies (total: 644; 491 outpatient studies, 153 inpatient studies). This included 4 examinations that were ordered by the patient's physician but not performed by our staff. The majority of the CEUS examinations (n = 583; 90.5%) were regularly scheduled procedures ordered by clinical specialists from our center (77.3%) or other centers (11.8%); by general practitioners (on their own initiative) (0.8%); or by other figures (0.6%). The remaining 61 examinations (9.5%) were unscheduled procedures done on the initiative of a radiologist following conventional sonography (US). Fewer than half (47.8%) of the examinations were requested as first-line assessments. The others were ordered to clarify inconclusive findings generated by conventional US (30%) or by a more sophisticated imaging study (CT, MRI, PET) (16.1%) or to resolve discrepancies between CT, MRI, and/or PET findings (6%). CEUS is a relatively noninvasive, low-cost imaging study that is simple to perform and requires no particular patient preparation. This may explain its increasing use to clarify doubts raised by conventional US and other more sophisticated imaging studies.

Effective drug delivery, in vitro and in vivo, by carbon-based nanovectors noncovalently loaded with unmodified Paclitaxel.

Many new drugs have low aqueous solubility and high therapeutic efficacy. Paclitaxel (PTX) is a classic example of this type of compound. Here we show that extremely small (<40 nm) hydrophilic carbon clusters (HCCs) that are PEGylated (PEG-HCCs) are effective drug delivery vehicles when simply mixed with paclitaxel. This formulation of PTX sequestered in PEG-HCCs (PTX/PEG-HCCs) is stable for at least 20 weeks. The PTX/PEG-HCCs formulation was as effective as PTX in a clinical formulation in reducing tumor volumes in an orthotopic murine model of oral squamous cell carcinoma. Preliminary toxicity and biodistribution studies suggest that the PEG-HCCs are not acutely toxic and, like many other nanomaterials, are primarily accumulated in the liver and spleen. This work demonstrates that carbon nanomaterials are effective drug delivery vehicles in vivo when noncovalently loaded with an unmodified drug.

Primary oncocytic adenocarcinomas of the lung: a clinicopathologic, immunohistochemical, and molecular biologic analysis of 16 cases.

Sixteen cases of primary oncocytic adenocarcinomas of the lung are reported. The patients were 11 women and 5 men between the ages of 47 and 81 years (median, 75 years) with symptoms of cough, chest pain, and shortness of breath. Surgical staging disclosed 14 patients (88%) with stage I disease, 1 (6%) with stage II, and 1 (6%) with stage III. Histologically, all the cases displayed prominent oncocytic features with conventional growth patterns, including acinar, papillary, and bronchioloalveolar. Immunohistochemically, the tumors displayed positive staining for keratin 7, thyroid transcription factor-1, and mitochondrial antibody. Molecular studies showed 3 (20%) of 15 tumors with EGFR mutations and 3 additional cases with KRAS mutations. Clinical follow-up of at least 24 months was obtained in all patients and showed that 5 patients had recurrences, 2 patients died of tumor, and 2 other patients died of unrelated conditions. These cases represent an unusual variant of pulmonary adenocarcinoma.

Mig-6 is required for appropriate lung development and to ensure normal adult lung homeostasis.

Mitogen-inducible gene 6 [Mig-6; Errfi1 (ErbB receptor feedback inhibitor 1); RALT (receptor-associated late transducer); gene 33] is a ubiquitously expressed adaptor protein containing CRIB, SH3 and 14-3-3 interacting domains and has been shown to negatively regulate EGF signaling. Ablation of Mig-6 results in a partial lethal phenotype in which surviving mice acquire degenerative joint diseases and tumors in multiple organs. We have determined that the early lethality in Mig-6(-/-) mice occurs in the perinatal period, with mice displaying abnormal lung development. Histological examination of Mig-6(-/-) lungs (E15.5-P3) revealed reduced septation, airway over-branching, alveolar type II cell hyperplasia, and disturbed vascular formation. In neonatal Mig-6(-/-) lungs, cell proliferation increased in the airway epithelium but apoptosis increased in the blood vessels. Adult Mig-6(-/-) mice developed features of chronic obstructive pulmonary disease (COPD); however, when Mig-6 was inducibly ablated in adult mice (Mig-6(d/d)), the lungs were normal. Knockdown of MIG-6 in H441 human bronchiolar epithelial cells increased phospho-EGFR and phospho-AKT levels as well as cell proliferation, whereas knockdown of MIG-6 in human lung microvascular endothelial (HMVEC-L) cells promoted their apoptosis. These results demonstrate that Mig-6 is required for prenatal and perinatal lung development, in part through the regulation of EGF signaling, as well as for maintaining proper pulmonary vascularization.

Additional role of colour Doppler ultrasound imaging in intracystic breast tumours.

PURPOSE: Cystic breast lesions with a nonsimple appearance, either complicated or complex, pose unique diagnostic difficulties, in part owing to their potentially malignant nature. Current ultrasound classification systems are based on morphostructural aspects only. The objective of this paper is to highlight the adjunctive role of Doppler techniques. MATERIALS AND METHODS: Over a 1-year period, we prospectively evaluated 45 women with atypical breast cysts of type IV, V or VI according to the Chang classification. Forty patients were symptomatic, whereas the cyst was discovered as an incidental finding in five cases. Our assessment included morphostructural, angioarchitectural and flowmetric aspects. RESULTS: Twenty-three nontumoural lesions were managed conservatively. All 19 type-IV cysts and all four type-V cysts according to the Chang classification showed absence of signal flow at colour Doppler imaging. Among the 22 tumoural lesions, there were eight papillomas, one atypical ductal hyperplasia and 13 carcinomas. The eight papillomas showed single (four cases) or multiple (four cases) mural projections. The atypical ductal hyperplasia showed a single parietal nodule. Among the 13 carcinomas, patterns included mural projections in 11 cases, eccentric cystic wall thickening in one and coarse intracystic septa in one. Cystic content appeared clear in six papillomas and in the case of atypical ductal hyperplasia, whereas it exhibited fine echoes in two papillomas. Among the carcinomas, cystic content showed coarse echoes in two cases and fine echoes in 11. Intralesional calcifications were seen in three carcinomas. Posterior enhancement was present in all carcinomas, whereas none showed posterior shadowing. In three carcinomas, some small solid satellite nodules were evident. Colour Doppler imaging showed lack of flow in four papillomas and subtle flow in the remaining four papillomas and in the atypical ductal hyperplasia. All 13 carcinomas showed diffuse vascularity, with multiple sparse vessels and multiple vascular poles. The resistive index, measurable in 4/8 papillomas, was 0.43 on average. Spectral analysis was measured in all carcinoma cases, yielding a mean resistive index of 0.71. CONCLUSIONS: Intracystic breast tumours exhibit distinctive morphostructural and colour Doppler features that allow effective differentiation from nontumoural cysts. Frequently, a presumptive differentiation between papillomas and carcinomas can be achieved. Absence of flow signals represents an additional criterion for complicated/complex cysts, allowing conservative management. Vascularity indicates the need for excision or biopsy of the solid projections, even in cases with negative cytology.

Localization of connexins in neurons and glia cells of the Helix aspersa suboesophageal brain ganglia by immunocytochemistry.

The aim of the present study was to examine the distribution of cells expressing connexin 26 (Cx26) in the suboesophageal visceral, left and right parietal and left and right pleural ganglia of the snail Helix aspersa by immunocytochemistry. Altogether we have found approximately 452 immunoreactive neurons which represent the 4.7% of the total neurons counted. The stained large neurons (measured diameter 55-140 microm) occurred mostly on the peripheral surface of the ganglia while the small immunostained cells (5-25 microm diameter) were observed in groups near the neuropil. The number of large neurons giving positive Cx26-like immunostaining was small in comparison with that for medium (30-50 microm diameter) and small sized cells. The expression of Cx26 was also observed in the processes of glia cells localized among neurons somata and in the neuropil showing that the antiserum recognized epitopes in both protoplasmic and fibrous glia cells of Helix aspersa. The neuropils of all ganglia showed fibers densely immunostained. While we have observed a good specificity for Cx26-antiserum in neurons, a lack of reaction for Cx43 antiserum was observed in neurons and glia cells. The reaction for enolase antiserum in neurons was light and non-specific and a lack of reaction in glia cells and processes for GFAP antiserum was observed. Although the percentage of positive neurons for Cx26 antiserum was low is suggested that in normal physiological conditions or under stimulation the expression of connexin could be increased. The observed results can be considered of interest in the interpretation of Helix aspersa elemental two neuron networks synchronizing activity, observed under applied extremely low frequency magnetic fields.

Copper and zinc dismetabolism in the mouse brain upon chronic cuprizone treatment.

Recent reports describe successful treatment using copper chelation therapy in neurodegenerative animal models. However, the success claimed for chelation therapy in neurodegenerative diseases is still rather controversial. To acquire new information on copper metabolism/homeostasis, we utilized cuprizone, a very sensitive and selective copper-chelating agent with well-known neurotoxic properties, as a relevant chemical model in mice. Upon cuprizone treatment, mice developed a pronounced astrocytosis, with brain oedema and spongiosis characterised by vacuolisations of the neuropil predominantly in the white matter. In addition, cuprizone treatment severely altered copper and zinc homeostasis in the central nervous system (CNS) as well as in all other tissues examined, with increasing metal ion concentrations particularly in the CNS. Concomitant with this increase in the Cu and Zn concentration in the brain, metallothionein-I and -II were also highly immunoreactive in astrocyte, consistent with the astrocytosis and demyelination observed in our and other laboratories.

[Echographic evaluation of the thymus gland in childhood]. / Valutazione ecografica del timo nell'età pediatrica.

INTRODUCTION: The thymus is a linphoepithelial organ located mostly in the anterior mediastinum and, for a smaller part, in the neck. The gland is particularly developed in the fetus and in children, while it shrinks in young adults following an involution process. We investigated the US appearance of the thymus in normal pediatric subjects to gather information for use in pediatric patients with suspected thymus conditions, using a safe, irradiation-free, technique. MATERIAL AND METHODS: We performed a US examination of the anterior mediastinum and the neck in 30 children (14 males and 16 females) ranging in age 6 months to 11 years. We used a Sonora LOGIC 700 MD General Electrics unit with 7.5-13 MHz linear probes and acquired transverse and longitudinal scans on the chest wall and the neck, integrated with intercostal scans. RESULTS: The thymus had the same echogenicity as the liver parenchyma in 22 children (73.3%), lower echogenicity in 2 (6.6%, age range 6-12 months) and higher echogenicity with heterogeneous structure in 6 children (20%, age range 8-11 years). The gland was in central and symmetric localization in 20 children (66.6%) while it exhibited a slight deviation leftwards in 7 (23.3%) and rightwards in 3 children (10%). We considered as normal the following values: in the right lobe, 1.4 cm for the AP diameter and 2.5 cm for the longitudinal one; in the left lobe, 1.4 cm for the AP diameter and 2.9 cm for the longitudinal one. DISCUSSION AND CONCLUSION: Radiological studies of the thymus are really difficult to perform because the gland is extremely variable in size, extension and shape. The thymus has the same echogenicity as the liver parenchyma and lower echogenicity than the thyroid parenchyma. We believe that US is an effective technique for studying the thymus in all its involution stages and that provides similar information to CT and MRI. Also, US does not use radiations and needs no sedation, which improves safety for young patients.

Involvement of rodent prefrontal cortex subregions in strategy switching.

The present study examined whether inactivation of the prelimbic-infralimbic areas or the dorsal anterior cingulate area impairs strategy switching in the cheeseboard task. After implantation of a cannula aimed at either the prelimbic-infralimbic or dorsal anterior cingulate areas, all rats were tested in a spatial and a visual-cued version of the task. Some of the rats received the spatial version first, followed by the visual-cued version. The procedure for the other rats was reversed. Infusions of 2% tetracaine into the prelimbic-infralimbic or dorsal anterior cingulate areas did not impair acquisition of the spatial or visual-cued versions. However, inactivation of the prelimbic-infralimbic areas, but not the dorsal anterior cingulate area, impaired learning when rats were switched from one version to the other. These findings suggest that the prelimbic-infralimbic areas are involved in switching to new behavior-guiding strategies.

[Detection by a computer program of drug interactions in chronic patients. Its practical usefulness in a health center]. / Detección de interacciones medicamentosas en pacientes crónicos mediante un programa informático. Utilidad práctica en un centro de salud.

OBJECTIVES: To evaluate a computer programme which was used to detect drug interactions (DI) from the Long Treatment Cards (LTC) and to analyse the factors possibly linked to these interactions. DESIGN: An observational, descriptive study. SETTING: Primary Health Care: an urban Health Centre. PATIENTS: The reference context was 1,640 chronic patients being cared for at a nursing clinic. We selected 141 cases at random by taking 10 LTCs from each list. (Alpha risk = 0.05; Confidence Interval = 0.05). RESULTS: The sample was mainly feminine (2:1), with an average age of 67. The most common diagnosis was Diabetes or AHT. 55% had accumulated 4 or more medicines per card, with multiple medication most common among men. The programme enabled 58 drug interactions, affecting 34% of the LTCs, to be identified. CONCLUSIONS: Special attention should be paid to the LTCs with 7 or more drugs prescribed because of their association with DI and NIV. The programme's efficacy would increase, both if the DIs were more accurately defined and if the programme could be computerised and applied massively to chronic treatments.

The clinical use of 99m-Tc-labeled WBC scintigraphy in critically ill surgical and trauma patients with occult sepsis.

OBJECTIVE: To evaluate the clinical use of radionuclide-labeled white blood cell scintigraphy in the detection of focal sepsis. DESIGN: Prospective clinical study. SETTING: A medical/surgical 12-bed intensive care unit (ICU) in a university hospital. PATIENTS: 26 trauma and surgical patients affected by sepsis of unknown origin were studied. MEASUREMENTS AND RESULTS: After the usual diagnostic approach, patients were submitted to a total body scan by using the patient's leukocytes labeled with technetium-99m (99m-Tc) HMPAO; three scintigraphy were performed within 20 h of tracer injection; the result of scan was completed with all clinical and instrumental data, including ultrasound (US) arnd computed tomography (CT), and the diagnostic efficacy was demonstrated for each patient on discharge from the ICU. The scan was able to detect 20 sites of infection; it was possible to rule out 11 suspected sites; only in two cases was the result considered to be false positive or false negative; in two cases the result was considered to be uncertain. These results show the high sensitivity (95%), specificity (91%) and accuracy (94%) of the method. CONCLUSIONS: In ICU patients with sepsis, nuclear medicine can provide additional data, as the injection of radionuclide-labeled white blood cells (WBCs) allows the imaging of sites of infection. Analysis of our results suggests that scintigraphy with 99m-Tc-labeled WBCs can be considered a useful tool in the detection of the source of infection.

Rhythmic variations of P100 component of pattern-reversal visual evoked potentials.

Pattern-reversal visual evoked potentials (EPs) were recorded in seven adult subjects to assess the existence of rhythmic variations in processing visual information at a primary stage. During a session of two hours, sixty EPs were recorded on the left and right cerebral hemispheres. The amplitude of N75-P100 component was measured. Remarkable variations were found with a periodicity from 15 to 60 min in six out of seven subjects. No hemispheric differences were found in the rhythmic variations. The results are in agreement with the behavioral data which show ultradian variations in visual performance depending on a general activation oscillator.