Is there a role for adjuvant therapy in radiation-induced angiosarcoma of the breast? A case report and review of the literature.

BACKGROUND: Angiosarcoma (AS) of the breast is very rare, accounting for 1% of all soft tissue breast tumors. AS may present as primary tumors of the breast or as secondary lesions usually associated with previous radiotherapy. Commonly, secondary AS affects older women (median age 67-71 years) with a clinical history of breast cancer. The preferred site of onset of RIAS is the edge of radiation fields, where radiation doses and tumor necrosis may be heterogeneous, resulting in a DNA damage and instability. Radical surgery is the treatment of choice, but no clear consensus exists on surgical management of breast AS. CASE REPORT: We describe an atypical case of relapsed RIAS after radical mastectomy, treated with new surgery and, considering the higher risk of recurrence, subsequent adjuvant chemotherapy with weekly paclitaxel. CONCLUSIONS: The frequency of radiation-induced angiosarcomas (RIAS) after breast-conserving surgery and radiotherapy has been increased to 0.14-0.5% among long survivors. Nevertheless, even if RIAS continues to be prognostically an extremely unfavorable cancer due to a high rate of recurrence, distant spread, and median overall survival (OS) of about 60 months, the benefits of loco-regional breast radiotherapy are clearly higher than the risk in developing angiosarcoma.

A Phospholipid Profile at 4 Months Predicts the Onset of Celiac Disease in at-Risk Infants.

Celiac disease (CeD) is a multifactorial disease influenced by both genetic and environmental risk factors. CeD genetic components are mainly due to HLA class II genes, which account for approximately 40% of the disease heritability. The environmental factor is linked to gliadin ingestion. Despite genetic and epigenetic studies, the pathological molecular mechanism remains unclarified. The strong genetic component does not explain more than half of the hereditability; we identified several epigenetic features that contribute to the understanding of the missing hereditability. The lipid profile of infants has been proposed as a potential biomarker of CeD metabolism that can be measured before they exhibit developmental disorders and clinical symptoms. We suggest that the state of the host is a main factor for the abnormal immune response to gluten. Long before any exposure to the offending agent or any production of specific antibodies, several molecular mechanisms are differentially expressed in infants who will develop CeD compared to their peers matched for the same genetic profile. The present study explored the serum phospholipid profile of a group of infants at risk for celiac disease, followed up to 8 years to monitor the onset of CeD. We compared 30 patients who developed the disease with 20 age- and sex-matched peers with similar genetic profiles who did not develop the disease within 8 years. Serum phospholipids were analysed at 4 months, before exposure to gluten, and at 12 months of age, when none showed any marker of disease. In the 30 CeD patients, we also analysed the serum at the time of diagnosis (>24 months). The serum phospholipid profile was fairly constant across 4 and 12 months of age and, in CeD, up to 24-36 months. The phospholipid signature was dramatically different in infants who developed CeD when compared to that of control NY-CeD (Not Yet developing Celiac Disease) peers. We identified a specific serum phospholipid signature that predicts the onset of celiac disease in HLA at-risk infants years before the appearance of antibodies specific for CeD in the serum and before any clinical symptoms, even before gluten introduction into the diet at 4 months. Specifically, lysophosphatidylcholine, phosphatidylcholine, alkylacyl-phosphatidylcholine, phosphoethanolamines, phosphatidylserines, phosphatidylglycerol and phosphatidylinositol were found to be differentially represented in CeD versus NY-CeD. A set constituted by a limited number of alkylacyl-phosphatidylcholine and lyso-phosphatidylcholine, together with the duration of breast-feeding, allows the discrimination of infants who develop celiac disease before 8 years of age from those at a similar genetic risk who do not develop the disease. In addition to recent discovery, our paper unveiled a specifc phopholipid profile, able to discriminate infants who eventually develop celiac disease years before antibodies or clinical symptoms ensue.

On the validity of habitat as a predictor of genetic structure in aquatic systems: a comparative study using California water beetles.

Among freshwater organisms, water flow is frequently considered to be one of the most important environmental variables affecting life-history traits such as dispersal abilities and therefore genetic structure. Recent studies have suggested that habitat type alone as defined by water flow is predictive of genetic population differentiation, while others have advocated against broad generalizations in favour of more conservative, species-specific conclusions. If aquatic habitat type is predictive of population differentiation, then one would expect sympatric taxa that occupy the same aquatic habitat to converge on a similar genetic structure. We tested this prediction by examining the haplotype diversity, phylogeographical concordance, population connectivity and population isolation of three lotic water beetle species in southern California: Anacaena signaticollis, Eubrianax edwardsii and Stictotarsus striatellus. In addition to coarse habitat and geography, we also controlled for the potentially confounding factors of range size, method of dispersal and clade independence. Together, the species spanned extremes of genetic and phylogeographical structure in all measures examined, suggesting that a coarse dichotomy of aquatic habitat type is not predictive of genetic structure. While there is little question that water flow plays a major role in shaping the life-history traits of freshwater organisms, it is perilous to confer predictive properties to an artificially simplistic dichotomy or use it as a surrogate for other unmeasured variables.

[Solid pseudo papillary tumor of the pancreas: case report and literature review]. / Tumore solido pseudopapillare del pancreas. Caso clinico e revisione della letteratura.

Solid pseudopapillary neoplasm (SPT) of the pancreas is a rare exocrine tumor, for the first time described from Frantz et al. in 1959. Despite the increasing recognition of the tumor in this last year, its pathogenesis remain unclear. It occurs predominantly in young woman and behave in an indolent fashion, even when distant metastasis are present. The Authors report the case of a 24 years-old woman with an abdominal mass localized in retro-peritoneum, removed with body-tail of the pancreas and spleen, diagnosed as pancreatic SPT after histological examination.

Partial purification and MALDI-TOF MS analysis of UN1, a tumor antigen membrane glycoprotein.

UN1 is a membrane glycoprotein that is expressed in immature human thymocytes, a subpopulation of peripheral T lymphocytes, the HPB acute lymphoblastic leukemia (ALL) T-cell line and fetal thymus. We previously reported the isolation of a monoclonal antibody (UN1 mAb) recognizing the UN1 protein that was classified as "unclustered" at the 5th and 6th International Workshop and Conference on Human Leukocyte Differentiation Antigens. UN1 was highly expressed in breast cancer tissues and was undetected in non-proliferative lesions and in normal breast tissues, indicating a role for UN1 in the development of a tumorigenic phenotype of breast cancer cells. In this study, we report a partial purification of the UN1 protein from HPB-ALL T cells by anion-exchange chromatography followed by immunoprecipitation with the UN1 mAb and MALDI-TOF MS analysis. This analysis should assist in identifying the amino acid sequence of UN1.

Evaluation of hepatic metastases from colorectal carcinoma with MR-superparamagnetic iron oxide.

The purpose of this study was to compare the results obtained with superparamagnetic iron oxide-enhanced and unenhanced Magnetic Resonance at 1.5 T with that of spiral-computed tomography (CT) in order to select those patients suitable for liver resection; the intraoperative US (IOUS) comprised the gold standard. Thirty five candidates for liver resection with known colorectal neoplasm were studied; 26 patients underwent surgery, one patient underwent RF ablation and 8 of them were submitted to follow-up. MR examination was performed using a 1.5 T superconductive instrument, CT examination was performed on a Somatom-Plus (Siemens) scanner. Dimensions and number of the lesions were defined in all patients as well as the sensitivity of spiral CT and MR imaging, using either the plain technique or after Ferumoxides c.m.. In those patients submitted to surgery, results have been correlated to those of IOUS. From 26 patients, a total of 48 lesions were removed surgically. With CT, 34 lesions with 3 false positive cases were detected; 32 with plain MR imaging, while MR imaging with Ferumoxides detected 41 lesions. In the patients not submitted to surgery, MR iron-oxide imaging identified 15 lesions, while both plain MR imaging and CT showed 8 lesions. The smallest lesion was 6 mm. as shown by MR imaging with Ferumoxides. In the cases submitted to surgery, the CT sensitivity was 71%, plain MR imaging 66% and MR imaging with Ferumoxides 85%. In our experience, Ferumoxides-enhanced MR imaging of the liver shows increased sensitivity compared to plain and spiral-CT in the evaluation of hepatic metastases. We think that MR superparamagnetic iron oxide should be used in all patients selected for liver resection.

Primary cancer of the urinary bladder: CT evaluation of the T parameter with different techniques.

The evaluation of mural invasion (T) in primary urinary bladder carcinoma is important in the planning of an appropriate surgical or radiochemotherapeutic strategy. Previous investigators using computed tomography (CT) have evaluated the bladder filled with urine, urine opacified with iodinated contrast material, or air insufflation. The purpose of this trial was to establish which of these three techniques was the most accurate by comparing data obtained in postoperative staging (pT). Sixty-five patients with primary bladder cancer were enrolled, all of whom were studied by spiral CT with these three techniques. Patients were assigned to four stage groups: Ta-T1, T2-T3a, T3b, and T4. The results demonstrated total accuracies of 95% for the air-insufflated bladder, 90.5% for opacified urine, and 87% for noncontrast studies. In conclusion, the air-insufflated bladder is the more accurate technique in the evaluation of the T parameter in primary bladder cancer, especially in the first and third stage groups.

A partitioned likelihood analysis of swallowtail butterfly phylogeny (Lepidoptera:Papilionidae).

Although it is widely agreed that data from multiple sources are necessary to confidently resolve phylogenetic relationships, procedures for accommodating and incorporating heterogeneity in such data remain underdeveloped. We explored the use of partitioned, model-based analyses of heterogeneous molecular data in the context of a phylogenetic study of swallowtail butterflies (Lepidoptera: Papilionidae). Despite substantial basic and applied study, phylogenetic relationships among the major lineages of this prominent group remain contentious. We sequenced 3.3 kb of mitochondrial and nuclear DNA (2.3 kb of cytochrome oxidase I and II and 1.0 kb of elongation factor-1 alpha, respectively) from 22 swallowtails, including representatives of Baroniinae, Parnassiinae, and Papilioninae, and from several moth and butterfly outgroups. Using parsimony, we encountered considerable difficulty in resolving the deepest splits among these taxa. We therefore chose two outgroups with undisputed relationships to each other and to Papilionidae and undertook detailed likelihood analyses of alternative topologies. Following from previous studies that have demonstrated substantial heterogeneity in the evolutionary dynamics among process partitions of these genes, we estimated evolutionary parameters separately for gene-based and codon-based partitions. These values were then used as the basis for examining the likelihoods of possible resolutions and rootings under several partitioned and unpartitioned likelihood models. Partitioned models gave markedly better fits to the data than did unpartitioned models and supported different topologies. However, the most likely topology varied from model to model. The most likely ingroup topology under the best-fitting, six-partition GTR + gamma model favors a paraphyletic Parnassiinae. However, when examining the likelihoods of alternative rootings of this tree relative to rootings of the classical hypothesis, two rootings of the latter emerge as most likely. Of these two, the most likely rooting is within the Papilioninae, although a rooting between Baronia and the remaining Papilionidae is only nonsignificantly less likely.

Bladder cancer within a direct inguinal hernia: CT demonstration.

We present a case of a urothelial neoplasm arising within a direct bladder hernia in the inguinal canal. Bladder hernias are rarely found preoperatively and are exceptional sites of neoplasm. Spiral computed tomography with gaseous insufflation of the bladder demonstrated the bladder hernia and the extension of the neoplasm in the inguinal canal more accurately than other computed tomographic techniques with nonopacified and iodinated urine.

Overcoming resistance to chronomodulated 5-fluorouracil and folinic acid by the addition of chronomodulated oxaliplatin in advanced colorectal cancer patients.

The addition of oxaliplatin (L-OHP) to a 5-fluorouracil (5-FU)/ leucovorin (FA) regimen was retrospectively evaluated in 35 consecutive advanced colorectal cancer patients after progression of disease. L-OHP, 25 mg/m2/day, was infused from 10.00-22.00 with a peak flow at 16.00 while 5-FU, 700 mg/m2/day and FA, 150 mg/m2/day of the I-form or 300 mg/m2/day of the racemic form, from 22.00 to 10.00 with a nocturnal peak at 4.00, for 5 days every 3 weeks in 24 patients and for 4 days every 2 weeks in the other 11. Diarrhea and sensitive neuropathy were the most relevant types of toxicity (17% of patients). An objective response was achieved in 8/35 patients (23%) [95% CL 9-37], stabilization in 15 patients (43%) which included five minor responses, and progression in 12. There was no relevant difference in quality of life assessed with the EORTC QLQ C30+3 questionnaire before and after treatment. Median duration of response and median progression-free survival were 6 months; median overall survival was 11 months. This retrospective study showed that it is possible to reverse resistance to chronomodulated 5-FU by adding chronomodulated L-OHP to the previous regimen; comparison with different schedules of this combination should be performed in order to identify the best tolerated and active regimen as second-line treatment of advanced colorectal cancer.

The current state of insect molecular systematics: a thriving Tower of Babel.

Insect molecular systematics has undergone remarkable recent growth. Advances in methods of data generation and analysis have led to the accumulation of large amounts of DNA sequence data from most major insect groups. In addition to reviewing theoretical and methodological advances, we have compiled information on the taxa and regions sequenced from all available phylogenetic studies of insects. It is evident that investigators have not usually coordinated their efforts. The genes and regions that have been sequenced differ substantially among studies and the whole of our efforts is thus little greater than the sum of its parts. The cytochrome oxidase I, 16S, 18S, and elongation factor-1 alpha genes have been widely used and are informative across a broad range of divergences in insects. We advocate their use as standards for insect phylogenetics. Insect molecular systematics has complemented and enhanced the value of morphological and ecological data, making substantial contributions to evolutionary biology in the process. A more coordinated approach focused on gathering homologous sequence data will greatly facilitate such efforts.

Effects of two types of activity on the performance of second-, third-, and fourth-grade students on a test of concentration.

The appropriateness of recess in the elementary program continues to be questioned although generally it is believed to be useful by elementary principals despite a dearth of supportive data. This study was a developmental study of the effects of physical activity on concentration. Comparison of passive and directed physical education activities on the concentration of second-, third-, and fourth-grade children was made. The Woodcock-Johnson Test of Concentration showed better performance by the fourth grades and within Grade 4 in favor of the physical activity group. A structured physical activity or a classroom activity immediately prior to a concentration task was not detrimental to children in Grades 2 and 3. Fourth-grade children performed significantly better on a test of concentration after engaging in a physical activity.

Ciliary motility at light microscopy: a screening technique for ciliary defects.

To verify whether or not ciliary motility can be reliably assessed by light microscopy alone, we examined the nasal brushings of 53 patients with suspected ciliary dyskinesia and 10 healthy controls. The results of light microscopy were compared with cilia ultrastructure assessed with electron microscopy. Ciliary motility was significantly related with cilia ultrastructure. However, eight cases of lung disease due to bronchiectasis of unknown origin had immotile cilia on light microscopy, but normal ciliary ultrastructure on electron microscopy. Instances of normal and abnormal ultrastructure were detected in one case with motile cilia. There was an 83% agreement between electron microscopy and light microscopy. Sensitivity and specificity of light microscopy were 92% and 80%, respectively. In conclusion, light microscopy evaluation of ciliary motility does not appear to be a reliable screening test for ciliary dyskinesia because it does not quantify ciliary beat activity, which is a criterion for deranged ciliary motion. A complete evaluation of ciliary ultrastructure together with in vivo, if applicable, or in vitro function test (namely, the analysis of ciliary beat frequencies and/or waveform) is required for a definite diagnosis of ciliary dyskinesia.

Papilio phylogeny based on mitochondrial cytochrome oxidase I and II genes.

Butterflies of the genus Papilio have served as the basis for numerous studies in insect physiology, genetics, and ecology. However, phylogenetic work on relationships among major lineages in the genus has been limited and inconclusive. We have sequenced 2.3 kb of DNA from the mitochondrial cytochrome oxidase I and II genes (COI and COII) for 23 Papilio taxa and two outgroups, Pachliopta neptunus and Eurytides marcellus, in order to assess the potential of these genes for use in Papilio phylogenetics and to examine patterns of gene evolution across a broad taxonomic range. Nucleotide and amino acid variation is distributed heterogeneously, both within and between genes. Structural features of the proteins are not always reliable predictors of variation. In a combined analysis, these sequences support a nearly fully resolved topology within subgenera and species groups, though higher level relationships among species groups require additional study. The most noteworthy findings are that neither Papilio alexanor nor P. xuthus belongs in the machaon group and that the subgenus Pterourus is paraphyletic with respect to the subgenus Pyrrhosticta. We leave relationships among members of the phorcas species group as a trichotomy. These two protein coding genes, particularly COI, show excellent performance in resolving relationships at the level of species and species groups among Papilionidae. We strongly endorse a similar approach for future studies aimed at these levels.