Lymphoepithelioma-like carcinoma of the skin: A light-microscopic and immunohistochemical study

Cutaneous carcinoma histopathologically resembling nasopharyngeal carcinoma has been termed lymphoepithelioma-like carcinoma of the skin. We present an additional example of this rare cutaneous neoplasm that was located on the left temple of an 83-year-old woman. Serology for Epstein-Barr virus was negative, and exploration of the nasopharyngeal region disclosed no abnormalities. Histopathologically, the neoplasm consisted of a relatively well-circumscribed, dermal-hypodermal nodule composed of irregular aggregates of epithelial cells with vesicular nuclei, some of them in mitosis, and scant cytoplasm. A dense lymphocytic infiltrate was present within the neoplastic aggregates, obscuring the epithelial component, and at scanning magnification, the lesion closely resembled cutaneous lymphoma or pseudolymphoma. There was local sebaceous differentiation. Immunohistochemistry showed positivity in the epithelial component for AE1/AE3 and AEB-903 cytokeratins and negativity for 8–18 cylokeratins. The inflammatory infiltrate was positive for leukocyte common antigen, UCHL-1, L-26, Leu-22, and OPD-4 in variable proportions. Scattered cells within this inflammatory infiltrate were also positive for S-100 protein, vimentin, HAM-56, and MAC-387. In situ hybridization investigations for the presence of Epstein-Barr virus genomic DNA yielded negative results. Lymphoepithelioma-like carcinoma of the skin is a distinct cutaneous neoplasm of unknown histogenesis, although some foci of adnexal differentiation have been found in some specimens. The possibility of cutaneous metastasis from occult nasopharyngeal carcinoma should be ruled out.
Requena L, Sánchez Yus E, Jiménez E, Roo E. Lymphoepithelioma-like carcinoma of the skin: A light-microscopic and immunohistochemical study.     

Estimating neuron dendritic length in 3D from total vertical projections and from vertical slices

The recently developed method of total vertical projections is illustrated to estimate the total dendritic length of a human Substantia Nigra neuron. Next, the length of the different orders of dendritic branches, and the mean segment length for each order - commonly regarded as important parameters in neuron physiology - are also estimated. Finally, it is shown how to estimate the mean dendritic length in a population of neurons from vertical slices of arbitrary and unknown thickness. Being unbiased and highly efficient, the proposed methods offer interesting alternatives to current procedures used for the metric analysis of neuron arborizations.     

Physical and spectroscopic methods for the evaluation of the interactions of antimitotic agents with tubulin.

The physico-chemical methods for the study of the binding of ligands to tubulin are examined in-depth, emphasizing the assumptions on which they are based and their limitations. The criteria of specificity and linkage to protein self-association are presented. It is shown that, of the direct equilibrium binding techniques, Hummel-Dreyer gel permeation chromatography and rapid ultracentrifugation are applicable only when binding is not linked to protein self-association. Disc filtration is valid only when the reverse unbinding reaction is very low. Binding linked to protein self-association can be measured by batch gel permeation or by dialysis equilibrium. The indirect techniques, such as fluorescence perturbation or difference absorption spectroscopy are discussed in terms of the assumptions on which they are based. They are shown to be used best only after characterization of the binding by direct techniques. Equilibrium binding parameters can also be deduced from careful kinetic experiments. Comparison of calorimetrically measured enthalpies of binding to van't Hoff enthalpies derived from equilibrium measurements indicates that the method of choice is calorimetric, while comparison with van't Hoff analysis can reveal the existence of reaction steps not detected by equilibrium measurements. Use of other indirect approaches, such as titration of an enzymic activity, can also lead to the detection of additional steps. The criteria are set up for the proper data analysis of ligand binding linked to protein self-association and the selection of the proper mode of linkage. It is shown how the thermodynamic contributions of various moieties of a ligand can be established by a rational structural modification of the ligand and the proper analysis of the binding measurements, in which all non-specific entropic contributions are taken into account. It is demonstrated also how a similar analysis of binding data can lead to conclusions about the reaction pathway from a comparison of equilibrium thermodynamic measurements on judiciously modified ligand molecules.     

Seizures with Onset in the Sensorimotor Face Area: Clinical Patterns and Results of Surgical Treatment in 20 Patients

Summary: It is not generally appreciated that intractable seizures involving the face area are amenable to surgical treatment. Twenty patients with onset of sensorimotor seizures in the face area of the pre- and postcentral gyri have been studied and surgically treated since 1948. Seizures started in the face, tongue, or throat, followed by diverse patterns depending on spread of seizure activity. Two patients had epilepsia partialis continua; 6 had either tonic or atonic drop attacks. All patients had pre- and postcentral face area resections, 12 in the dominant hemisphere. In addition, 3 had more extensive postcentral removal, 7 had temporal lobe, and 4 had small separate or contiguous frontal or parietal resection. Because the seizures were not sufficiently reduced by the first operation, 6 required reoperation; 4 of these patients had residual epileptiform activity on electrocorticogram (ECoG) after the first resection. Three patients had new neurologic signs that did not return to the preoperative level, but in 2 of them the deficit related mainly to higher resection in the central area. All but 2 of these 20 patients had at least moderate seizure reduction. Corticectomy can be performed for treatment of seizures arising in the lower central area and usually does not lead to significant permanent neurologic deficit.     

Stimulation of tumor growthin vitro andin vivo by suramin on the VX2 model

Suramin is an antitrypanosomal compound with confirmed efficacy against several human malignancies. It is generally assumed that its mechanism of action includes the interaction with different growth factors, unlike most of the anticancer drugs. Its anticancer activity has not been testedin vivo against squamous cell carcinoma. The purpose of this study was to assess the efficacy and toxicity of suraminin vivo andin vitro on the VX2 tumor model at therapeutic monitored plasma concentrations. We determined the pharmacokinetics of suramin in rabbits, and modelized its administration in order to obtain plasma concentrations between 150 and 300 μg/ml throughout the treatment course of 3 weeks. Under these conditions, antitumor effects of suramin were evaluatedin vivo by comparing liver tumor involvement in suramin-treated and control rabbits. Liver involvement was quantified by image analysis andin vitro effects were also determined at the same concentrations.In vivo, suramin promoted liver tumor growth significantly (p<0.05), compared to untreated controls.In vitro, suramin significantly stimulated tumor cell growth at concentrations above 200 μg/ml (p<0.01). Suramin may have stimulatory effects on tumor growth in squamous cell carcinoma at relevant plasma drug concentrations. Caution should be taken in further trials in patients with squamous cell carcinomas.     

Blood pressure on arising, morning blood pressure surge and blood pressure variability in white coat hypertensives and in matched normotensives and sustained hypertensives.

INTRODUCTION: It is still controversial whether subjects with white-coat hypertension (WCHT) exhibit higher cardiovascular risk compared to normotensive subjects (NT). In subjects with WCHT it is not known whether the abnormal blood pressure (BP) reaction in the office also occurs at other times of day, particularly on arising and immediately after waking, i.e. the times at which the majority of cardiovascular events are reported to occur. OBJECTIVE AND METHODS: To evaluate with 24h ambulatory BP measurement the values of morning BP surge, BP on arising and BP variability in subjects with WCHT in comparison with age-, gender- and weight-matched normotensives (BP) and untreated sustained hypertensives (BP). RESULTS: Groups of BP, WCHT and BP were matched for age, gender and body weight: BP: n=69, age 49 +/- 7 years, 54 % female, BMI 26 +/- 1, casual BP 126/79 +/- 5/4 mmHg, daytime BP 124/80 +/- 6/6 mmHg; WCHT: n=74, age 52 +/- 8 years, 57% female, BMI 26 +/- 2, casual BP 152/95 +/- 7/7 mmHg, daytime BP 126/80 +/- 5/6 mmHg; HT: n=79, age 53 +/- 7 years, 56% female, BMI 27 +/- 2, casual BP 154/97 +/- 9/8 mmHg, daytime BP 143/89 +/- 12/10 mmHg. Of the three groups, subjects with WCHT exhibited BP on arising (121/81 +/- 13/8 mmHg) similar to that of NTs (120/80 +/- 13/9 mmHg, NS), both significantly lower than that of HTs (137/92 +/- 17/10 mmHg, p < 0.01), suggesting the absence of an alerting BP reaction in WCHT at that time. By contrast, subjects with WCHT showed higher values of systolic morning BP surge vs. NTs (25 +/- 10 vs. 22 +/- 11 mmHg, p < 0.05), both lower than that observed in hypertensives (33 +/- 11 mmHg, p < 0.01 vs. NT and WCHT) and greater daytime variability (systolic BP standard variation), i.e. 12 2 vs. 10 +/- 2 mmHg, p < 0.05, both lower than that observed in hypertensives (14 +/- 3 mmHg, p < 0.01 vs. NT and WCHT). CONCLUSIONS: Although subjects with WCHT did not show any alerting blood pressure reaction on arising, morning BP surge and BP variability were greater in these subjects than in control normotensives, although lower than sustained hypertensives. Although this is still speculative, we cannot exclude the possibility that even a slight increase in morning BP surge might in the long term constitute an additional load on the circulation that could increase cardiovascular risk in subjects with WCHT compared to matched normotensives.     

Use of stereotactic PET images in dosimetry planning of radiosurgery for brain tumors: clinical experience and proposed classification.

We developed a technique that allows the routine integration of PET in stereotactic neurosurgery, including radiosurgery. We report our clinical experience with the combined use of metabolic (i.e., PET) and anatomic (i.e., MRI and CT) images for the radiosurgical treatment of brain tumors. We propose a classification describing the relative role of the information provided by PET in this multimodality image-guided approach. METHODS: Between December 1999 and March 2003, 57 patients had stereotactic PET as part of their image acquisition for the planning of gamma knife radiosurgery. Together with stereotactic MRI and CT, stereotactic PET images were acquired on the same day using either (18)F-FDG or (11)C-methionine. PET images were imported in the planning software for the radiosurgery dosimetry, and the target volume was defined using the combined information of PET and MRI or CT. To analyze the specific contribution of the PET findings, we propose a classification that reflects the strategy used to define the target volume. RESULTS: The patients were offered radiosurgery with PET guidance when their tumor was ill-defined and we anticipated some limitation of target definition on MRI alone. This represents 10% of the radiosurgery procedures performed in our center during the same period of time. There were 40 primary brain lesions, 7 metastases, and 10 pituitary adenomas. Abnormal PET uptake was found in 62 of 72 targets (86%), and this information altered significantly the MRI-defined tumor in 43 targets (69%). CONCLUSION: The integration of PET in radiosurgery provides additional information that opens new perspectives for the optimization of the treatment of brain tumors.     

Colonization with methicillin-resistant Staphylococcus aureus after liver transplantation.

Methicillin-resistant Staphylococcus aureus (MRSA) is a frequent cause of infection after orthotopic liver transplantation (OLT). Colonization with MRSA is associated with a higher risk of infection. Previous studies have shown a high prevalence of MRSA colonization among OLT candidates. However, the risk of colonization with MRSA after OLT is still unclear. The objective of this study was to estimate the incidence and the factors associated with colonization with MRSA after OLT. This was a prospective cohort study including patients submitted to OLT between the years 2000 and 2002. Surveillance cultures of nasal swab specimens were performed within the 1st 72 hours of hospital admission and, subsequently, on weeks 2, 6, 13, and 26. Patients whose baseline cultures revealed nasal carriage of MRSA were excluded. A total of 60 patients were included in the study. The median follow-up was 72 days. A total of 9 patients (15%) became colonized. In multiple logistic regression analyses, the use of a urinary catheter for > or =5 days (P = .006), postoperative bleeding at the surgical site (P = .009), and preoperative use of fluoroquinolones (P = .08) were associated with a higher risk of colonization. Patients without any of these risk factors did not become colonized. In conclusion, nasal carriage of MRSA is frequently acquired after OLT. Periodic postoperative screening for MRSA carriage should be an integral component in programs designed to reduce nosocomial MRSA transmission in these patients. Further studies are needed to set up and validate a predictive model that could allow targeting postoperative screening to high-risk OLT recipients.     

Feasibility of cranio-spinal axis radiation with the Hi-Art tomotherapy system.

BACKGROUND AND PURPOSE: Helical tomotherapy can eliminate the need for junction lines. The goal of this study is to evaluate tomotherapy in the delivery of CSA radiation and measurement of plan quality using physical parameters in comparing conventional (CSA-RT) and helical tomotherapy (CSA-TOMO) plans. PATIENTS AND METHODS: CSA-TOMO and CSA-RT plans were created for dosimetric comparison. Integral dose values were calculated. The ratios D50% (dose received by 50% of the organ at risk's volume) and D10% (dose received by 10% of the organ at risk's volume) were calculated representing large volumes and small volumes of organs at risk receiving significant dose. RESULTS: When considering D50% and D10%, CSA-TOMO has a dosimetric advantage over CSA-RT for most organs at risk. The body integral dose was higher for the CSA-TOMO plan by approximately 6.5%. CONCLUSIONS: Tomotherapy is a feasible alternative for treatment of CSA. Analysis shows that tomotherapy improves dose ratios over conventional radiation for most organs at risk. The impact of a small increase in whole body integral dose is unknown. Long-term follow-up will be needed to answer this question as others have argued of the possibility of increased risk of secondary malignancies due to delivery of radiotherapy with IMRT.