Search

Background: There has been an increase in the utilization of single-fraction stereotactic body radiation therapy (SBRT) to treat thoracic structures, but there have been few reports describing toxicity outcomes with this treatment., Methods: We evaluated 119 sites (114 patients) with no prior history of thoracic radiation were treated from 10/1/2003 to 10/27/2008 with single-fraction SBRT to thoracic structures. The median dose to the gross tumor volume was 2400 cGy (range 1800-2400 cGy), as was the median dose to the planning target volume (range 1600-2400 cGy). A detailed review of thoracic toxicities was performed to include pneumonitis or Grade 2 or higher esophageal and bronchial toxicity. In addition, we retrospectively contoured the esophagus and bronchus of 48 patients treated in 2004-2005, prior to the establishment of dose constraints to determine the range of doses that these structures received., Results: Of the contoured patients, the median dose to the hottest 1cc (D1cc) of the esophagus was 1250 cGy (range 158-2572 cGy). The median bronchial D1cc was 1101 cGy (range 260-2211 cGy). At a median follow-up of 11.6 months, there were seven Grade 2 or higher esophageal toxicities, including one Grade 3 and one Grade 4 toxicities. There were two bronchial toxicities, one Grade 2 and one Grade 3. There were no cases of pneumonitis., Conclusions: High-dose single-fraction SBRT is well tolerated to the thoracic region, with most patients tolerating high doses to central structures without significant toxicity.

Background and Purpose: In mammalian heart, connexin43 (Cx43) represents the predominant connexin in the working myocardium. As the beta-adrenoceptor is involved in many cardiac diseases, we wanted to clarify the pathway by which beta-adrenoceptor stimulation may control Cx43 expression., Experimental Approach: Cultured neonatal rat cardiomyocytes were stimulated with isoprenaline. Cx43 expression as well as activation of p38 mitogen-activated protein kinase (MAPK), p42/44 MAPK, JUN NH(2)-terminal kinase (JNK) and nuclear translocation of the transcription factors activator protein 1 (AP1) and CRE-binding protein (CREB) were investigated. Additionally, we assessed Cx43 expression and distribution in left ventricular biopsies from patients without any significant heart disease, and from patients with either congestive heart failure [dilated cardiomyopathy (DCM)] or hypertrophic cardiomyopathy (HCM)., Key Results: Isoprenaline exposure caused about twofold up-regulation of Cx43 protein with a pEC(50) of 7.92 +/- 0.11, which was inhibited by propranolol, SB203580 (4-(4-fluorophenyl)-2-(4-methylsulphinylphenyl)-5-(4-pyridyl)-1H-imidazole) (p38 inhibitor), PD98059 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one) (MAPK 1 kinase inhibitor) (Alexis Biochemicals, San Diego, CA, USA) or cyclosporin A. Similar findings were obtained for Cx43 mRNA. Furthermore, Cx43 up-regulation was accompanied by phosphorylation of p38, p42/44 and JNK, and by translocation of AP1 and CREB to the nucleus. Analysis of Cx43 protein and mRNA in ventricular biopsies revealed that in patients with DCM, Cx43 content was significantly lower, and in patients with HCM, Cx43 content was significantly higher, relative to patients without any cardiomyopathy. More importantly, Cx43 distribution also changed with more Cx43 being localized at the lateral border of the cardiomyocytes., Conclusion and Implication: Beta-adrenoceptor stimulation up-regulated cardiac Cx43 expression via a protein kinase A and MAPK-regulated pathway, possibly involving AP1 and CREB. Cardiomyopathy altered Cx43 expression and distribution.

Background: To the authors' knowledge, the indications for adjuvant treatment in acinic cell carcinoma (AciCC) of the parotid gland have not been elucidated to date. The aim of the current study was to determine patterns of failure and adverse prognostic features., Methods: Between March of 1989 and August of 2006, 35 patients underwent surgery at Memorial Sloan-Kettering Cancer Center for AciCC of the parotid gland and had their clinical and pathologic features retrospectively analyzed at the primary site. All cases were reviewed by 2 head and neck pathologists. Five-year estimates of survival outcomes were performed, followed by univariate analysis of potential prognostic features., Results: The T classifications were as follows: T1 in 46% of patients, T2 in 23% of patients, T3 in 18% of patients, and T4 in 9% of patients. Three patients had cervical lymph node involvement. All patients underwent surgery as their primary treatment. Approximately 63% of patients (n = 22) received radiation treatment. The median follow-up time for surviving patients was 59.9 months. Five-year estimates of disease-free survival (DFS), overall survival (OS), and local control were 85%, 90%, and 90%, respectively. Of the clinical variables tested, clinical extracapsular extension (ECE), facial nerve sacrifice, and lymph node involvement were found to be significantly associated with a detriment in DFS and OS (P < .05). Positive surgical margins, histologic ECE, >2 mitoses per 10 high-power fields (HPF), atypical mitosis, vascular invasion, perineural invasion, pleomorphism, and necrosis were associated with adverse DFS (P < .05). All of these variables except for vascular invasion (P = .377) and perineural invasion (P = .07) were associated with OS. If high-grade tumors were defined on the basis of high mitotic activity (>2 mitoses/10 HPF) and/or tumor necrosis, high-grade carcinomas had a significantly lower DFS and OS (P = .001)., Conclusions: AciCC had a low treatment failure rate, and a large number of patients could be considered candidates for surgery only. A histologic grading system was devised to help stratify patients for adjuvant treatment.

Purpose: To present our single-institution experience of intensity-modulated radiotherapy (IMRT) for oral cavity cancer., Methods and Materials: Between September 2000 and December 2006, 35 patients with histologically confirmed squamous cell carcinoma of the oral cavity underwent surgery followed by postoperative IMRT. The sites included were buccal mucosa in 8, oral tongue in 11, floor of the mouth in 9, gingiva in 4, hard palate in 2, and retromolar trigone in 1. Most patients had Stage III-IV disease (80%). Ten patients (29%) also received concurrent postoperative chemotherapy with IMRT. The median prescribed radiation dose was 60 Gy., Results: The median follow-up for surviving patients was 28.1 months (range, 11.9-85.1). Treatment failure occurred in 11 cases as follows: local in 4, regional in 2, and distant metastases in 5. Of the 5 patients with distant metastases, 2 presented with dermal metastases. The 2- and 3-year estimates of locoregional progression-free survival, distant metastasis-free survival, disease-free survival, and overall survival were 84% and 77%, 85% and 85%, 70% and 64%, and 74% and 74%, respectively. Acute Grade 2 or greater dermatitis, mucositis, and esophageal reactions were experienced by 54%, 66%, and 40% of the patients, respectively. Documented late complications included trismus (17%) and osteoradionecrosis (5%)., Conclusion: IMRT as an adjuvant treatment after surgical resection for oral cavity tumors is feasible and effective, with promising results and acceptable toxicity.

Purpose: To evaluate long-term outcomes and toxicity in patients with unresectable paranasal sinus carcinoma treated with radiotherapy, with or without chemotherapy., Methods and Materials: Between January 1990 and December 2006, 39 patients with unresectable Stage IVB paranasal sinus carcinoma were treated definitively with chemotherapy plus radiotherapy (n = 35, 90%) or with radiotherapy alone (n = 4, 10%). Patients were treated with three-dimensional conformal radiotherapy (n = 18, 46%), intensity-modulated radiotherapy (n = 12, 31%), or conventional radiotherapy (n = 9, 23%) to a median treatment dose of 70 Gy. Most patients received concurrent platinum-based chemotherapy (n = 32, 82%) and/or concomitant boost radiotherapy (n = 29, 74%)., Results: With a median follow-up of 90 months, the 5-year local progression-free survival, regional progression-free survival, distant metastasis-free survival, disease-free survival, and overall survival were 21%, 61%, 51%, 14%, and 15%, respectively. Patients primarily experienced local relapse (n = 25, 64%), mostly within the irradiated field (n = 22). Nine patients developed neck relapses; however none of the 4 patients receiving elective neck irradiation had a nodal relapse. In 13 patients acute Grade 3 mucositis developed. Severe late toxicities occurred in 2 patients with radionecrosis and 1 patient with unilateral blindness 7 years after intensity-modulated radiation therapy (77 Gy to the optic nerve). The only significant factor for improved local progression-free survival and overall survival was a biologically equivalent dose of radiation >/=65 Gy., Conclusions: Treatment outcomes for unresectable paranasal sinus carcinoma are poor, and combined-modality treatment is needed that is both more effective and associated with less morbidity. The addition of elective neck irradiation may improve regional control.

Background: We report on the effectiveness of a standardized perioperative care process for lowering surgical site infection (SSI) rates among children with stoma closure at a tertiary-care public pediatric teaching hospital in Mexico City., Methods: All consecutive children with stoma closure operated on between November 2003 and October 2005 were prospectively followed for 30 days postoperatively. We conducted a before-after study to evaluate standardized perioperative bowel- and abdominal-wall care process results on SSI rates., Results: Seventy-one patients were operated on, and all completed follow-up. SSI rates declined from 42.8% (12/28) before to 13.9% (6/43) after the standardization procedure (relative risk (RR) = 3.1; 95% confidence interval (CI) = 1.3-7.2; p = 0.006). SSI independently associated risk factors comprised peristomal skin inflammation >3 mm (odds ratio (OR) = 9.6; 95% CI = 1.8-49.6; p = 0.007) and intraoperative complications (OR = 13.3; 95% CI = 1.4-127.2; p = 0.02). Being operated on during the after-study period was shown to be a protective factor against SSI (OR = 0.2; 95% CI = 0.4-0.97; p = 0.04)., Conclusion: Standardization was able to reduce SSI rates threefold in children with stoma closure in a short period of time.

Sternechus subsignatus Boheman (Curculionidae: Sternechini) is one of the primary Curculionidae species that reduces soybean yield in Brazil. Initially, outbreaks were reported in southern Brazil in 1973; but, more recent, outbreaks were reported in Bahia (summer 1997-1998) and Maranhão (summer 2003-2004), two states in northeastern Brazil. A putative related species, S. pinguis (Fabricius), was first detected in Salta Province, Argentina. The objective of this study was to evaluate intraspecific molecular polymorphisms of geographically distinct Sternechus populations. Randomly amplified polymorphic DNA (RAPD) profiles and partial mitochondrial cytochrome B (CytB) gene sequences were used to determine whether individual soybean stalk weevils were one of two different species and to infer pest invasion pattern. Putative S. pinguis and S. subsignatus populations were collected in San Agustin (Cruz Alta, Tucumán Province, Argentina) and different sampling sites in the Brazilian states of Paraná, Bahia and Maranhão. Polymorphic bands were obtained by RAPD and analyzed by Dice coefficients. Populations from southern Brazil were more closely related genetically to an Argentinean group than the populations sampled in northeastern Brazil. The Londrina Co., Brazil population displayed the highest intra-population genetic similarity. Most of the soybean stalk weevils collected from San Agustin, Tucumán, Argentina were divergent from those collected in Brazil. Sequencing and parsimony analysis of CytB did not differentiate specimens collected in Argentina and Brazil. Thus, our data show that soybean stalk weevil outbreaks and population increases in northeastern Brazil involved local genotypes.

Phragmidium violaceum causes leaf rust on the European blackberry (Rubus fruticosus L. aggregate). Multiple strains of this pathogen have been introduced into southern Australia for the biological control of at least 15 taxa of European blackberry, a nonindigenous, invasive plant. In climates conducive to leaf rust, the intensity of disease varies within and among infestations of the genetically variable host. Genetic markers developed from the selective amplification of microsatellite polymorphic loci were used to assess the population genetic structure and reproductive biology of P. violaceum within and among four geographically isolated and diseased infestations of the European blackberry in Victoria, Australia. Despite the potential for long-distance aerial dispersal of urediniospores, there was significant genetic differentiation among all populations, which was not associated with geographic separation. An assessment of multilocus linkage disequilibrium revealed temporal and geographic variation in the occurrence of random mating among the four populations. The presence of sexual spore states and the results of genetic analyses indicated that recombination, and potentially random migration and genetic drift, played an important role in maintaining genotypic variation within populations. Recombination and genetic differentiation in P. violaceum, as well as the potential for metapopulation structure, suggest the need to release additional, genetically diverse strains of the biocontrol agent at numerous sites across the distribution of the Australian blackberry infestation for maximum establishment and persistence.

Purpose: To analyze the recent experience of patients with adenoid cystic carcinoma treated with radiation therapy at Memorial Sloan-Kettering Cancer Center., Methods and Materials: From 1990 to 2004, a total of 59 patients with a diagnosis of primary adenoid cystic carcinoma of the head and neck received radiation therapy at our institution. The subsite distribution was oral cavity, 28% (n = 17); paranasal sinuses, 22% (n = 13); parotid, 14% (n = 8); submandibular, 14% (n = 8); oropharynx, 10% (n = 6); sublingual, 3% (n = 2); nasopharynx, 3% (n = 2); and other, 5% (n = 3). T Stage distribution was T1, 34% (n = 20); T2, 19% (n = 11); T3, 14% (n = 8); and T4, 34% (n = 20). Twenty-nine percent of patients (n = 17) were treated with intensity-modulated radiation therapy; 25% (n =15), with three-dimensional conformal therapy, and the remainder, with conventional techniques. Ninety percent (n = 53) of patients received treatment including the base of skull., Results: Median follow-up for surviving patients was 5.9 years. Five-year and 10-year rates of local control and distant metastases-free survival were 91%/81% and 81%/49%, respectively. Five-year and 10-year rates of disease-free and overall survival were 76%/40% and 87%/65%, respectively. On univariate analysis, stage T4 (p = 0.004) and gross/clinical nerve involvement (p = 0.002) were associated with decreased progression free survival, whereas stage T4 and lymph node involvement were associated with decreased overall survival (p = 0.046 and p < 0.001, respectively)., Conclusions: Radiation therapy in combination with surgery produces excellent rates of local control, although distant metastases account for a high proportion of failures. Routine treatment to the base of skull reduces the significance of histologic perineural invasion, but major nerve involvement remains an adverse prognostic factor.

Introduction: Primary central nervous system lymphoma is a very rare condition in pediatric patients., Case Report: We describe the case of a 10-year old girl who presented with acute bilateral vision impairment. At the time of presentation, the only positive finding was optic disk swelling, and the brain MRI scan was normal. Seventeen months later, she developed a large-cell non-Hodgkin lymphoma in the brain, with no evidence of neoplasia elsewhere. Immunodeficiencies and Epstein-Barr virus infection could not be demonstrated. The patient was successfully treated with a combination of cyclophosphamide, etoposide, vincristine, methotrexate, and cytarabine, plus intrathecal chemotherapy. Craniospinal irradiation was not used., Outcome: The patient's condition is still in remission 68 months after completing the treatment., Conclusion: This case is the only non-Hodgkin lymphoma with primary central nervous system location treated in our institution in the last 10 years and represents less than 0.5% of our non-Hodgkin lymphoma series. Due to its rare occurrence, not much is known about the clinical features and treatment outcome of primary central nervous system lymphoma in pediatric patients.

Indigenous to Europe, the blackberry rust fungus Phragmidium violaceum was introduced to Australia and subsequently appeared in New Zealand, with the most recent authorised introductions to Australia specifically for the biological control of European blackberry. Markers for 'selective amplification of microsatellite polymorphic loci' (SAMPL) were developed for studying the population genetics of P. violaceum. Modification of one of the two SAMPL primers with a HaeIII adapter (H) revealed significantly greater levels of genetic variation than primers used to generate AFLPs, the latter revealing little or no variation among 25 Australasian and 19 European isolates of P. violaceum. SAMPL was used to describe genetic variation among these 44 isolates of P. violaceum from 51 loci generated using primer pairs (GACA)4 +H-G and R1+H-G. The European isolates were more diverse than Australasian isolates, with 37 and 22 % polymorphic loci, respectively. Cluster analysis revealed geographic clades, with Australasian isolates forming one cluster separated from two clusters comprising the European isolates. However, low bootstrap support at these clades suggested that Australian isolates had not differentiated significantly from European isolates since the first record of P. violaceum in Australia in 1984. In general, the results support two hypotheses. First, that the population of P. violaceum in Australia was founded from a subset of individuals originating from Europe. Second, that P. violaceum in New Zealand originated from the Australian population of P. violaceum, probably by wind dispersal of urediniospores across the Tasman Sea. The application of SAMPL markers to the current biological control programme for European blackberry is discussed.

Data on spinal ependymomas are sparse, and prognostic factors remain controversial. The primary aim of this study is to review a historical cohort, with large patient numbers and long follow-up, and provide estimates of time to progression (TTP) and survival after progression. As a secondary aim, we assess the effects of potential prognostic variables. Thirty-seven patients with spinal cord ependymomas received postoperative radiation therapy from 1955 to 2001. The influences of radiation dose, extent of resection, Karnofsky performance score, tumor location, and multifocality were assessed in univariate analyses by using the Cox proportional hazards model. The median follow-up for patients who did not fail was 121 months (range, 8-312 months). Kaplan-Meier estimates of 5-, 10-, and 15-year percentage progression free are 75%+/-7.4%, 50%+/-9.1%, and 46%+/-9.3%, respectively. Median TTP, for those who recurred, is 68 months (range, 2-324 months), with 12 of 21 failures occurring after five years. Of the prognostic factors examined, only greater extent of resection significantly correlated with longer TTP (P=0.02). Local relapse rates for spinal ependymomas are higher than previously cited, with a large proportion of failures occurring more than five years after diagnosis. Extensive surgical resection correlates with longer time to recurrence, and we thus recommend maximal excision while avoiding surgical morbidity. The overall high rate of recurrence leads us to recommend radiation to doses of 45 to 54 Gy for all patients who do not have gross total resections, and long, close follow-up.

Bands of dsRNA were detected in five out of seven isolates of the entomopathogenic fungus Metarhizium flavoviride. The identity of these bands was proven by RNase and S1-nuclease treatments. The transference of dsRNA between isolates (from CG291 to CG442) was successfully carried out through forced heterokaryons. Isogenic strains, with or without dsRNA, were submitted to virulence tests against the grasshopper Rhammatocerus schistocercoides. In contrast to what has been found in some phytopathogenic fungi, these dsRNA fragments did not cause hypovirulence to M. flavoviride.

In this paper we examined the conidial attachment of Metarhizium anisopliae on the southern green stink bug, Nezara viridula, using the exuvia and nymphal stage of the host as a substrate for M. anisopliae conidiospores. Initial studies using fluorescein isothiocyanate (FITC)-labeled conidia examined the differential binding of conidia to various sites on the cuticle. Both the topography and the chemistry of the cuticle affected conidial adhesion. Conidia were trapped in areas containing large numbers of setae (e.g., antennal tips, apical portions of tibia and tarsi). Chemical treatments to remove the cuticle proteins did not affect conidial adhesion, but solvent extraction of cuticular lipids significantly reduced the adhesion of M. anisopliae spores. Germination of M. anisopliae conidia attached to N. viridula cuticle was much less than conidia attached to other insect cuticle substrates. After a 24-hr incubation, only 5-20% of the conidia produced detectable germ tubes. The aldehyde (E)-2-decenal, a primary component of the stink bug scent gland, was detected in cuticle extracts and found to be selectively fungistatic to certain entomopathogenic fungi, including M. anisopliae. The hydrocarbon fraction (nC13 and nC21 to nC31 hydrocarbon series) served as a binding substrate for M. anisopliae, but conidia did not degrade these hydrocarbons and did not use them as a carbon source.