Adult-type rhabdomyosarcoma (RMS) has been classically defined as a pleomorphic sarcoma with desmin expression occurring in adult patients. To reevaluate this entity, we analyzed a series of 57 cases using immunohistochemistry for desmin, myogenin, alpha smooth muscle actin, h-caldesmon, pankeratin AE1/AE3, epithelial membrane antigen (EMA), S100 protein, CD34, MDM2, and CDK4. In this series, there were 36 men and 21 women aged from 22 to 87 years (median: 59). Tumors were mainly located in the lower limbs (27 cases), trunk wall (15 cases), and upper limbs (10 cases). Most tumors were deeply located (51/54) with a size from 1 to 30 cm (median: 8 cm). Cases were classified in 3 histologic categories: spindle cell RMS (25 cases), pleomorphic RMS (16 cases), and mixed type (16 cases). Forty-one tumors were grade 3 and 16 grade 2. Immunohistochemistry showed that every case was positive for desmin and myogenin. Alpha smooth muscle actin was positive in 21%, pankeratin AE1/AE3 in 20%, and CD34 in 13.2%. Treatment modalities and follow-up were available in 46 cases. Median follow-up was 60.9 months. Eight patients developed a local recurrence and 16 a distant metastasis with a 5-year overall survival rate of 52.6% and a 5-year metastasis-free survival of 62.9%. The only predictive factor for metastasis was histologic grade. In conclusion, adult-type RMS is a rare sarcoma occurring mainly in the extremities and trunk wall with 2 main histologic patterns, spindle cell, and pleomorphic patterns, which represent the end of the spectrum of a single entity.

ABSTRACT: Nuclear localization signals (NLSs) are stretches of residues within a protein that are important for the regulated nuclear import of the protein. Of the many import pathways that exist in yeast, the best characterized is termed the 'classical' NLS pathway. The classical NLS contains specific patterns of basic residues and computational methods have been designed to predict the location of these motifs on proteins. The consensus sequences, or patterns, for the other import pathways are less well-understood. In this paper, we present an analysis of characterized NLSs in yeast, and find, despite the large number of nuclear import pathways, that NLSs seem to show similar patterns of amino acid residues. We test current prediction methods and observe a low true positive rate. We therefore suggest an approach using hidden Markov models (HMMs) to predict novel NLSs in proteins. We show that our method is able to consistently find 37% of the NLSs with a low false positive rate and that our method retains its true positive rate outside of the yeast data set used for the training parameters. Our implementation of this model, NLStradamus, is made available at: http://www.moseslab.csb.utoronto.ca/NLStradamus/

BACKGROUND: Cardiopulmonary resuscitation guidelines imply the use of epinephrine/adrenaline during cardiopulmonary arrest. However, in cardiac arrest situations resulting from coronary artery spasm (CAS), the use of epinephrine/adrenaline could be deleterious. METHODS AND RESULTS: A 49-year-old patient underwent an emergency coronarography with an attempt to stent the coronary arteries. Radiologic imaging revealed a positive methylergonovine maleate (Methergine, Novartis Pharmaceuticals, East Hanover, NJ) test, with subocclusive CAS in several coronary vessels leading to electromechanical dissociation. Cardiopulmonary resuscitation was performed, and intracoronary boluses of isosorbide dinitrate were given to treat CAS. Epinephrine/adrenaline was not administered during resuscitation. Spontaneous circulation was obtained after cardioversion for ventricular fibrillation, and the patient progressively regained consciousness. CONCLUSION: Resuscitation guidelines do not specify the use of trinitrate derivatives in cardiac arrest situations caused by CAS. The pros and cons of the use of nitrates and epinephrine/adrenaline during cardiac arrest caused by CAS are analyzed in this case report.

BACKGROUND: In mammals, a temporal disconnection between mRNA transcription and protein synthesis occurs during late steps of germ cell differentiation, in contrast to most somatic tissues where transcription and translation are closely linked. Indeed, during late stages of spermatogenesis, protein synthesis relies on the appropriate storage of translationally inactive mRNAs in transcriptionally silent spermatids. The factors and cellular compartments regulating mRNA storage and the timing of their translation are still poorly understood. The chromatoid body (CB), that shares components with the P. bodies found in somatic cells, has recently been proposed to be a site of mRNA processing. Here, we describe a new component of the CB, the RNA binding protein HuR, known in somatic cells to control the stability/translation of AU-rich containing mRNAs (ARE-mRNAs). METHODOLOGY/PRINCIPAL FINDINGS: Using a combination of cell imagery and sucrose gradient fractionation, we show that HuR localization is highly dynamic during spermatid differentiation. First, in early round spermatids, HuR colocalizes with the Mouse Vasa Homolog, MVH, a marker of the CB. As spermatids differentiate, HuR exits the CB and concomitantly associates with polysomes. Using computational analyses, we identified two testis ARE-containing mRNAs, Brd2 and GCNF that are bound by HuR and MVH. We show that these target ARE-mRNAs follow HuR trafficking, accumulating successively in the CB, where they are translationally silent, and in polysomes during spermatid differentiation. CONCLUSIONS/SIGNIFICANCE: Our results reveal a temporal regulation of HuR trafficking together with its target mRNAs from the CB to polysomes as spermatids differentiate. They strongly suggest that through the transport of ARE-mRNAs from the CB to polysomes, HuR controls the appropriate timing of ARE-mRNA translation. HuR might represent a major post-transcriptional regulator, by promoting mRNA storage and then translation, during male germ cell differentiation.

BACKGROUND: The management of desmoid tumours, previously based on strategies employed for sarcomas, should be reassessed, given the morbidity of interventions used in their treatment. METHODS: Long-term follow-up (median 123months) of a series of 106 treated patients with 69 primary and 37 recurrent desmoids, in order to study natural history and outcome. RESULTS: Desmoids typically evolved actively over a median period of 3years, and stabilised thereafter. Recurrences or progression most commonly occurred between 14 and 17months. Risk factors for recurrence were presentation (primary vs. recurrent), gender, tumour location and resection margins. However, survival was independent from these factors, with equivalent survival whether resection had been performed or not. Tumour control and functional outcome depended on location and presentation. Functional impairment was proportional to number of operations and whether patients had received radiotherapy. Recurrences were observed in 12/23 patients after radiotherapy. CONCLUSION: Desmoids are relatively indolent tumours needing different approaches than sarcomas. Direct surgery is advisable only in primary lower trunk wall/girdle locations. Wait-and-see and medical treatment is preferable in other types of presentations.

INTRODUCTION:: A 10-year experience with breast reconstruction in a university hospital was recently reviewed. The purpose of this study was to determine the subtypes of breast reconstructive procedures and to evaluate the frequency and change in technique over time of free TRAM (transverse rectus abdominis muscle) flap breast reconstruction performed at one institution. Trends in the development of the procedure over this period were also reviewed. MATERIALS & METHODS:: Between November 1994 and September 2004, a 10-year retrospective chart review was conducted. The indications for mastectomy and reconstruction were determined. The median age was 48 (range 31-66). The range of follow-up was 2 to 71 months, with a median of 19.5 months. The mean follow-up was 23.5 months. Outcome data were grouped into 2 consecutive 5-year periods (period 1: 1994-1998; period 2: 1999-2004) and evaluated for changes over time in techniques and outcome. Statistical analysis (Decision Analyst, Inc., STATS Statistics software, version 1.1, 1998) was performed using the difference between 2 proportions module to assess the probability of a significant difference in the data for period 1 and period 2 parameters. RESULTS:: Over a 10-year period, 117 patients underwent breast reconstruction. This consisted of 12 pedicle procedures (11.3%), including 1 bipedicle flap (0.9%) and 2 bilateral pedicle procedures (1.8%). There were 3 latissimus dorsi pedicle flaps (2.8%). Sixteen patients (15.1%) received tissue expander or implant reconstructions. Of the 117 patients, 79 underwent free flap breast reconstruction. Of the 79 free-flap patients, 22 (27.8%) had bilateral procedures, for a total of 101 free flaps performed in these 79 patients. Fifty-two patients underwent immediate reconstruction (65.8%) and 25 were delayed (31.6%) reconstructions using either deep inferior epigastric artery perforator (DIEP) flaps (4 = 3.9%) or free TRAM flaps (97 = 96.0%). A muscle-sparing technique was used in 43 of the 97 free TRAM flaps (44.3%). The preferred vascular inflow was the internal mammary artery, which was used in 66 out of 101 flaps (65.3%). The rate of anastomotic revision (arterial and venous) was 4.9%. The majority of cases used a 2.5-mm venous coupler (65.3%). In 2 of the free TRAM cases, there was insufficient volume to establish the patients preexisting volume. Therefore, at the patient's request, immediate implants were used to augment the reconstruction. The average hospital stay was 8.13 days, and the average intensive care stay was 4.59 days. When assessed for trends over time, we noted a reduction in our hospital length of stay and our ICU length of stay. CONCLUSION:: The experience with free tissue breast reconstruction reveals predominant use of the TRAM flap. This is justified by the reliability of this flap and the advances in achieving esthetic breast reconstruction. Additionally, we have begun performing DIEP free-flap reconstructions. Our clinical practice has evolved concurrent with standards of care, as noted by the increase in use of muscle-sparing techniques and the reduction in the use of dextran. We do not routinely use therapeutic anticoagulation in our cases. Our hospital length of stay and average intensive care length of stay have also decreased over time, consistent with a system-wide effort to increase the efficiency of healthcare delivery.

BACKGROUND: Docetaxel and mitoxantrone are considered first-line chemotherapeutic options in patients with hormone-refractory prostate cancer (HRPC), but their clinical effectiveness in a second-line setting is unknown. Therefore, the authors conducted a population-based retrospective study to establish activity and tolerability of second-line docetaxel or mitoxantrone in HRPC. METHODS: The study included 68 patients who had failed androgen ablation therapy and who received docetaxel and mitoxantrone in either sequence. Clinical efficacy in terms of median overall survival (OS), progression-free survival (PFS), posttreatment prostate-specific antigen (PSA) decline of >/= 50% and treatment-related toxicity were evaluated. RESULTS: Of 68 patients, 35 received docetaxel followed by mitoxantrone, and 33 received mitoxantrone followed by docetaxel. Both groups were comparable for recognized pretreatment prognostic factors. Patients who received docetaxel first-line had a trend toward longer median OS compared with patients treated with second-line docetaxel after mitoxantrone failure (22 mos, 95% confidence interval [CI], 17.2-26.8 mos vs. 15 mos, 95% CI, 10.4-19.6 mos). Median number of second-line chemotherapy cycles was 3 and median PFS survival was 2-3 months in both groups. Second-line docetaxel produced a higher PSA response compared with mitoxantrone (38% vs. 12%, P = 0.012), but this did not translate to a survival benefit. Both second-line docetaxel and mitoxantrone were associated with a high frequency of treatment-related adverse events that resulted in dose reduction, delay, or discontinuation (64% and 46% of patients, respectively). CONCLUSIONS: Study results favored docetaxel given up-front for patients with HRPC considered suitable for further chemotherapy. Second-line docetaxel or mitoxantrone had limited efficacy and tolerability. Patients who are candidates for second-line chemotherapy, should be enrolled into clinical trials. Cancer 2006.(c) 2006 American Cancer Society.

BACKGROUND AND PURPOSE: To evaluate intraoperative brachytherapy in the management of soft tissue sarcomas involving neurovascular structures, its impact on local control and complications. PATIENTS AND METHODS: Between 01/1989 and 12/2002, 98 patients received an intraoperative implant in conjunction with conservative surgery. Brachytherapy was part of the initial treatment (79 cases) or performed in recurrent disease (19 cases). We studied primary sarcomas involving neurovascular structures treated with conservative surgery and intraoperative brachytherapy (n=6) or intraoperative brachytherapy and external irradiation (n=73). Conservative surgery was performed as first treatment (51 cases), after chemotherapy (21 cases) and after primary external radiation (seven cases). Brachytherapy was performed according to Paris system rules. Patients were loaded with Iridium 192 (64 cases) or connected to a Microselectron PDR (15 cases). Mean dose given by brachytherapy was 20Gy. Mean dose given of external radiotherapy was 46Gy. RESULTS: With a median follow-up of 58 months, 5-year actuarial survival was 69% and local free disease at 5 years was 90%. Acute side-effects occurred in 22/79 requiring surgical repair in 10 patients. Late side-effects occurred in 35/79. No patient required amputation for complications. Prognostic factors were studied for the occurrence of acute and late side-effects and local control. CONCLUSIONS: Intraoperative brachytherapy is efficient with excellent local control rates in soft tissue sarcomas presenting with neurovascular involvement and offers an acceptable conservative option.

The association of cardiac tamponade and pulmonary embolism has not previously been described. We report the case of a patient, who presented with such an association, due to an underlying pulmonary carcinoma. When a major pericardial effusion is associated with pulmonary hypertension, some echocardiographic signs of tamponade may appear, such as a moderate right ventricular collapse, or the absence of a paradoxical septum. The presence of pulmonary hypertension in this context of tamponade may have paradoxically saved the life of this patient.