Interobserver variability in clinical target volume delineation in tangential breast irradiation: a comparison between radiation oncologists and radiation therapists.

AIMS: The delineation of target volumes has been radiation oncologist led. If radiation therapists were to undertake this task, work processes may be more efficient and the skills set of radiation therapy staff broadened. This study was undertaken to quantify interobserver variability of breast target volumes between radiation oncologists and radiation therapists. MATERIALS AND METHODS: The planning computed tomography datasets of 30 patients undergoing tangential breast radiotherapy were utilised. Four radiation oncologists and four radiation therapists independently contoured the clinical target volume (CTV) of the breast on planning computed tomography using a written protocol. The mean CTV volumes and the mean distance between centres of volume (COV) were determined for both groups to determine intergroup variation. Each of the radiation oncologists' readings in turn has been used as the gold standard and compared with that of the radiation therapists. The concordance index for each patient's CTV was determined relative to the gold standard for each group. A paired t-test was used for statistical comparison between the groups. An intraclass correlation coefficient was calculated to measure the agreement between the radiation oncologist and radiation therapist groups. RESULTS: The mean concordance index was 0.81 for radiation oncologists and 0.84 for radiation therapists. The intraclass correlation coefficient for the mean volume was 0.995 (95% confidence interval 0.981-0.998) between radiation oncologist- and radiation therapist-contoured volumes. The intraclass correlation for the mean difference between radiation oncologists' and radiation therapists' COV was 0.999 (95% confidence interval 0.999-1.000). CONCLUSIONS: Interobserver variability between radiation oncologists and radiation therapists was found to be low. Radiation therapists could potentially assume the role of CTV voluming for breast radiotherapy provided a standardised contouring protocol is in place.

Amyloidosis of the breast mimicking recurrence in a previously treated early breast cancer.

Amyloid involvement of the breast is infrequently reported and may have clinical and radiological features suspicious for a primary breast malignancy. We describe a case of amyloid of the breast in which asymptomatic mammographic findings were suspicious for locally recurrent disease in a patient with previously treated breast cancer.

Regional radiotherapy may improve outcomes in patients with early stage breast cancer undergoing breast conservation therapy.

BACKGROUND: Breast conservation therapy (BCT) is recommended as standard management of early breast cancer. The aim of this study was to retrospectively evaluate the results of BCT to identify prognostic factors predictive of treatment outcomes. PATIENTS AND METHODS: Four hundred and ninety-eight eligible women with unilateral stage I-II breast cancer who had undergone BCT were analyzed. RESULTS: The cumulative incidence of local recurrence (LR) was 1.9% and 3.7% at 3- and 5-years respectively. The 5-year disease-free, cancer-specific, and overall survival (DFS, CSS, OS) were 80.0%, 87.3% and 85.4% respectively. Significant independent predictors for LR included young age and absence of chemotherapy. Regional nodal radiotherapy was significantly associated with improved DFS and OS. CONCLUSION: Our results confirmed the efficacy of BCT in the treatment of early breast cancer and indicated that inclusion of regional nodal areas within the radiotherapy field might be beneficial in the BCT setting, particularly for patients with adverse risk features.

DELETION MAPPING OF CRITICAL REGION FOR HYPOSPADIAS, PENOSCROTAL TRANSPOSITION AND IMPERFORATE ANUS ON HUMAN CHROMOSOME 13.

BACKGROUND: The 13q-deletion syndrome causes human congenital birth defects due to the loss of regions of one long arm of human chromosome 13. A distal critical region for severe genitourinary and anorectal birth defects in the region of 13q32.2-34 has been suggested; we sought to narrow this critical region. METHODS: From patients with karyotypes revealing haploinsufficiency for distal chromosome 13q and their parents, peripheral blood was obtained and lymphocytes were immortalized for DNA isolation. Genetic and molecular cytogenetic methods were used to map deletions. Patient and parental samples were genotyped with a panel of 20 microsatellite markers spanning 13q31.3 qter and deletions identified by loss of heterozygosity. Deletions were also mapped using a panel of 35 BAC clones from the same region as probes for fluorescence in-situ hybridization on patient lymphoblastoid metaphase preparations. The data were synthesized and a deletion map defining the critical region was generated. RESULTS: Eight patients with known deletions around 13q32qter and their parents were analyzed, and categorized into three groups: three patients with anorectal and genitourinary anomalies (hypospadias, penoscrotal transposition), four male patients without anorectal and genitourinary anomalies, and one XY patient with ambiguous genitalia without anorectal anomalies. We mapped the critical region for anorectal and genitourinary anomalies to a approximately 9.5-Mb interval of 13q33.3-q34 delineated by markers D13S280-D13S285; this spans approximately 8% of the chromosome and contains 20 annotated genes CONCLUSION: The critical region of chromosome 13q mediating genitourinary/anorectal anomalies has been mapped, and will be narrowed by additional patients and further mapping. Identification of the gene(s) mediating these syndromic genitourinary defects should further our knowledge of molecular mediators of non-syndromic hypospadias, penoscrotal transposition and anorectal malformations.

Mantle planning: report of the Australasian Radiation Oncology Lymphoma Group film survey and consensus guidelines.

The purpose of the present paper was to measure the variation in mantle planning in Australia and New Zealand. A chest X-ray (CXR) of a patient in the supine position with a neck node marked by wire was sent to every radiation oncologist in Australia and New Zealand. They were to mark on the CXR the lung blocks that they would use to treat this patient, assuming that the patient had stage IA Hodgkin's disease. These marks were compared with a small sample of radiologists who were asked to define the mediastinum on the same CXR. Radiation oncologists were also asked to complete a short questionnaire about other modifications to their treatment fields and their experience with this technique. One hundred and six films were sent out and 44 radiation oncologists replied. There was a maximum variation in the placement of their lung blocks of 6 cm. Half of the lung blocks were within a 2-cm range. One respondent said they would not use a mantle field to treat this patient. Mediastinal coverage was inadequate in at least 50% of cases. There was a very large variation in mantle field planning practices within Australia and New Zealand. For this reason Australasian Radiation Oncology Lymphoma Group has produced consensus guidelines for mantle block design. These are appended to the present paper.

Three-dimensional dose distribution of tangential breast irradiation: results of a multicentre phantom dosimetry study.

BACKGROUND AND PURPOSE: One aspect of good radiotherapeutic practice is to achieve dose homogeneity. Dose inhomogeneities occur with breast tangent irradiation, particularly in women with large breasts. MATERIALS AND METHODS: Ten Australian radiation oncology centres agreed to participate in this multicentre phantom dosimetry study. An Alderson radiation therapy anthropomorphic phantom with attachable breasts of two different cup sizes (B and DD) was used. The entire phantom was capable of having thermoluminescent dosimeters (TLD) material inserted at various locations. Nine TLD positions were distributed throughout the left breast phantom including the superior and inferior planes. The ten centres were asked to simulate, plan and treat (with a prescription of 100 cGy) the breast phantoms according to their standard practice. Point doses from resultant computer plans were calculated for each TLD position. Measured and calculated (planning computer) doses were compared. RESULTS: The dose planning predictability between departments did not appear to be significantly different for both the small and large breast phantoms. The median dose deviation (calculated dose minus measured dose) for all centres ranged from 2. 3 to 5.3 cGy on the central axis and from 2.1 to 7.5 cGy for the off-axis planes. The highest absolute dose was measured in the inferior plane of the large breast (128.7 cGy). The greatest dose inhomogeneity occurred in the small breast phantom volume (median range 93.2-105 cGy) compared with the large breast phantom volume (median range, 100.1-107.7 cGy). There was considerable variation in the use (or not) of wedges to obtain optimized dosimetry. No department used 3D compensators. CONCLUSION: The results highlight areas of potential improvement in the delivery of breast tangent radiotherapy. Despite reasonable dose predictability, the greatest dose deviation and highest measured doses occurred in the inferior aspects of both the small and large breast phantoms.

Osteolymphoma (primary bone lymphoma): an Australian review of 70 cases. Australasian Radiation Oncology Lymphoma Group (AROLG).

BACKGROUND: To examine prognostic factors, treatment outcomes and design future studies for Osteolymphoma (OL)--also known as primary bone lymphoma. METHODS: Between 1979 and 1993, 70 patients with OL were treated in nine Australian centres. The effect of patient-, tumour-, and treatment-related factors on local control, distant disease-free survival and overall survival were assessed by multivariate analysis. RESULTS: Most patients (94%) received radiotherapy (RT) (median dose 40 Gy) and 56% received chemotherapy. Multifocal disease was present in 20% of patients. The five year rates of overall survival and local control were 59% and 82%. Although there was a trend towards better results with the addition of chemotherapy, on multivariate analysis, there were no factors identified which appeared to impact upon overall and disease-free survival. Among the distant recurrences, there was a high proportion in bone (33%). Six patients suffered pathological fractures after treatment. CONCLUSION: High rates of local control were achieved by RT, but the overall survival remains relatively poor, worse than nodal lymphoma. The natural history of the disease suggests that OL may be a distinct entity, different to nodal lymphomas, so the results of clinical trials in nodal lymphoma may not be relevant to OL. Prospective studies could define the outcome of combined modality therapy and set a benchmark for testing further proposals, as well as improving our knowledge of the clinical features of OL.

Isolation of Geobacter species from diverse sedimentary environments.

In an attempt to better understand the microorganisms responsible for Fe(III) reduction in sedimentary environments, Fe(III)-reducing microorganisms were enriched for and isolated from freshwater aquatic sediments, a pristine deep aquifer, and a petroleum-contaminated shallow aquifer. Enrichments were initiated with acetate or toluene as the electron donor and Fe(III) as the electron acceptor. Isolations were made with acetate or benzoate. Five new strains which could obtain energy for growth by dissimilatory Fe(III) reduction were isolated. All five isolates are gram-negative strict anaerobes which grow with acetate as the electron donor and Fe(III) as the electron acceptor. Analysis of the 16S rRNA sequence of the isolated organisms demonstrated that they all belonged to the genus Geobacter in the delta subdivision of the Proteobacteria. Unlike the type strain, Geobacter metallireducens, three of the five isolates could use H2 as an electron donor for Fe(III) reduction. The deep subsurface isolate is the first Fe(III) reducer shown to completely oxidize lactate to carbon dioxide, while one of the freshwater sediment isolates is only the second Fe(III) reducer known that can oxidize toluene. The isolation of these organisms demonstrates that Geobacter species are widely distributed in a diversity of sedimentary environments in which Fe(III) reduction is an important process.

Microbial degradation of hydrochlorofluorocarbons (CHCl2F and CHCl2CF3) in soils and sediments.

The ability of microorganisms to degrade trace levels of the hydrochlorofluorocarbons HCFC-21 and HCFC-123 was investigated. Methanotroph-linked oxidation of HCFC-21 was observed in aerobic soils, and anaerobic degradation of HCFC-21 occurred in freshwater and salt marsh sediments. Microbial degradation of HCFC-123 was observed in anoxic freshwater and salt marsh sediments, and the recovery of 1,1,1-trifluoro-2-chloroethane indicated the involvement of reductive dechlorination. No degradation of HCFC-123 was observed in aerobic soils. In some experiments, HCFCs were degraded at low (parts per billion) concentrations, raising the possibility that bacteria in nature remove HCFCs from the atmosphere.

Phylogenetic analysis of dissimilatory Fe(III)-reducing bacteria.

Evolutionary relationships among strictly anaerobic dissimilatory Fe(III)-reducing bacteria obtained from a diversity of sedimentary environments were examined by phylogenetic analysis of 16S rRNA gene sequences. Members of the genera Geobacter, Desulfuromonas, Pelobacter, and Desulfuromusa formed a monophyletic group within the delta subdivision of the class Proteobacteria. On the basis of their common ancestry and the shared ability to reduce Fe(III) and/or S0, we propose that this group be considered a single family, Geobacteraceae. Bootstrap analysis, characteristic nucleotides, and higher-order secondary structures support the division of Geobacteraceae into two subgroups, designated the Geobacter and Desulfuromonas clusters. The genus Desulfuromusa and Pelobacter acidigallici make up a distinct branch within the Desulfuromonas cluster. Several members of the family Geobacteraceae, none of which reduce sulfate, were found to contain the target sequences of probes that have been previously used to define the distribution of sulfate-reducing bacteria and sulfate-reducing bacterium-like microorganisms. The recent isolations of Fe(III)-reducing microorganisms distributed throughout the domain Bacteria suggest that development of 16S rRNA probes that would specifically target all Fe(III) reducers may not be feasible. However, all of the evidence suggests that if a 16S rRNA sequence falls within the family Geobacteraceae, then the organism has the capacity for Fe(III) reduction. The suggestion, based on geological evidence, that Fe(III) reduction was the first globally significant process for oxidizing organic matter back to carbon dioxide is consistent with the finding that acetate-oxidizing Fe(III) reducers are phylogenetically diverse.

Desulfuromonas palmitatis sp. nov., a marine dissimilatory Fe(III) reducer that can oxidize long-chain fatty acids.

Studies on the microorganisms living in hydrocarbon-contaminated sediments in San Diego Bay, California led to the isolation of a novel Fe(III)-reducing microorganism. This organism, designated strain SDBY1, was an obligately anaerobic, non-motile, non-flagellated, gram-negative rod. Strain SDBY1 conserves energy to support growth from the oxidation of acetate, lactate, succinate, fumarate, laurate, palmitate, or stearate. H2 was also oxidized with the reduction of Fe(III), but growth with H2 as the sole electron donor was not observed. In addition to various forms of soluble and insoluble Fe(III), strain SDBY1 also coupled growth to the reduction of fumarate, Mn(IV), or S0. Air-oxidized minus dithionite-reduced difference spectra exhibited peaks at 552.8, 523.6, and 422.8 nm, indicative of c-type cytochrome(s). Strain SDBY1 shares physiological characteristics with organisms in the genera Geobacter, Pelobacter, and Desulfuromonas. Detailed analysis of the 16S rRNA sequence indicated that strain SDBY1 should be placed in the genus Desulfuromonas. The new species name Desulfuromonas palmitatis is proposed. D. palmitatis is only the second marine organism found (after D. acetoxidans) to oxidize multicarbon organic compounds completely to carbon dioxide with Fe(III) as an electron acceptor and provides the first pure culture model for the oxidation of long-chain fatty acids coupled to Fe(III) reduction.

Fe(III) and S0 reduction by Pelobacter carbinolicus.

There is a close phylogenetic relationship between Pelobacter species and members of the genera Desulfuromonas and Geobacter, and yet there has been a perplexing lack of physiological similarities. Pelobacter species have been considered to have a fermentative metabolism. In contrast, Desulfuromonas and Geobacter species have a respiratory metabolism with Fe(III) serving as the common terminal electron acceptor in all species. However, the ability of Pelobacter species to reduce Fe(III) had not been previously evaluated. When a culture of Pelobacter carbinolicus that had grown by fermentation of 2,3-butanediol was inoculated into the same medium supplemented with Fe(III), the Fe(III) was reduced. There was less accumulation of ethanol and more production of acetate in the presence of Fe(III). P. carbinolicus grew with ethanol as the sole electron donor and Fe(III) as the sole electron acceptor. Ethanol was metabolized to acetate. Growth was also possible on Fe(III) with the oxidation of propanol to propionate or butanol to butyrate if acetate was provided as a carbon source. P. carbinolicus appears capable of conserving energy to support growth from Fe(III) respiration as it also grew with H2 or formate as the electron donor and Fe(III) as the electron acceptor. Once adapted to Fe(III) reduction, P. carbinolicus could also grow on ethanol or H2 with S0 as the electron acceptor. P. carbinolicus did not contain detectable concentrations of the c-type cytochromes that previous studies have suggested are involved in electron transport to Fe(III) in other organisms that conserve energy to support growth from Fe(III) reduction.(ABSTRACT TRUNCATED AT 250 WORDS)

Geobacter sulfurreducens sp. nov., a hydrogen- and acetate-oxidizing dissimilatory metal-reducing microorganism.

A dissimilatory metal- and sulfur-reducing microorganism was isolated from surface sediments of a hydrocarbon-contaminated ditch in Norman, Okla. The isolate, which was designated strain PCA, was an obligately anaerobic, nonfermentative nonmotile, gram-negative rod. PCA grew in a defined medium with acetate as an electron donor and ferric PPi, ferric oxyhydroxide, ferric citrate, elemental sulfur, Co(III)-EDTA, fumarate, or malate as the sole electron acceptor. PCA also coupled the oxidation of hydrogen to the reduction of Fe(III) but did not reduce Fe(III) with sulfur, glucose, lactate, fumarate, propionate, butyrate, isobutyrate, isovalerate, succinate, yeast extract, phenol, benzoate, ethanol, propanol, or butanol as an electron donor. PCA did not reduce oxygen, Mn(IV), U(VI), nitrate, sulfate, sulfite, or thiosulfate with acetate as the electron donor. Cell suspensions of PCA exhibited dithionite-reduced minus air-oxidized difference spectra which were characteristic of c-type cytochromes. Phylogenetic analysis of the 16S rRNA sequence placed PCA in the delta subgroup of the proteobacteria. Its closest known relative is Geobacter metallireducens. The ability to utilize either hydrogen or acetate as the sole electron donor for Fe(III) reduction makes strain PCA a unique addition to the relatively small group of respiratory metal-reducing microorganisms available in pure culture. A new species name, Geobacter sulfurreducens, is proposed.

Septic arthritis of the shoulder after mastectomy and radiotherapy for breast carcinoma.

We report five patients who developed septic arthritis of the shoulder after cancer of the ipsilateral breast had been treated by surgery and radiotherapy. Lymphoedema was present in all cases. The infections were not obvious, having subacute onsets, and delays in diagnosis led to destruction of the joint in all but one patient.

Anaerobic Oxidation of Toluene, Phenol, and p-Cresol by the Dissimilatory Iron-Reducing Organism, GS-15.

The dissimilatory Fe(III) reducer, GS-15, is the first microorganism known to couple the oxidation of aromatic compounds to the reduction of Fe(III) and the first example of a pure culture of any kind known to anaerobically oxidize an aromatic hydrocarbon, toluene. In this study, the metabolism of toluene, phenol, and p-cresol by GS-15 was investigated in more detail. GS-15 grew in an anaerobic medium with toluene as the sole electron donor and Fe(III) oxide as the electron acceptor. Growth coincided with Fe(III) reduction. [ring-C]toluene was oxidized to CO(2), and the stoichiometry of CO(2) production and Fe(III) reduction indicated that GS-15 completely oxidized toluene to carbon dioxide with Fe(III) as the electron acceptor. Magnetite was the primary iron end product during toluene oxidation. Phenol and p-cresol were also completely oxidized to carbon dioxide with Fe(III) as the sole electron acceptor, and GS-15 could obtain energy to support growth by oxidizing either of these compounds as the sole electron donor. p-Hydroxybenzoate was a transitory extracellular intermediate of phenol and p-cresol metabolism but not of toluene metabolism. GS-15 oxidized potential aromatic intermediates in the oxidation of toluene (benzylalcohol and benzaldehyde) and p-cresol (p-hydroxybenzylalcohol and p-hydroxybenzaldehyde). The metabolism described here provides a model for how aromatic hydrocarbons and phenols may be oxidized with the reduction of Fe(III) in contaminated aquifers and petroleum-containing sediments.

Stability of solutions of histamine acid phosphate after sterilization by heating in an autoclave.

Histamine acid phosphate (HAP) solutions are used in tests for asthma and also as positive controls in general allergenic testing. Previously these solutions have been sterilized, if at all, by filtration, thus limiting the shelf-life of the preparation and introducing some degree of uncertainty in their use. It is shown here that HAP solutions can be sterilized successfully by heating in an autoclave with little degradation and that subsequent storage of autoclaved solutions indicates a minimum shelf-life of 4 months.

Hydrogen and Formate Oxidation Coupled to Dissimilatory Reduction of Iron or Manganese by Alteromonas putrefaciens.

The ability of Alteromonas putrefaciens to obtain energy for growth by coupling the oxidation of various electron donors to dissimilatory Fe(III) or Mn(IV) reduction was investigated. A. putrefaciens grew with hydrogen, formate, lactate, or pyruvate as the sole electron donor and Fe(III) as the sole electron acceptor. Lactate and pyruvate were oxidized to acetate, which was not metabolized further. With Fe(III) as the electron acceptor, A. putrefaciens had a high affinity for hydrogen and formate and metabolized hydrogen at partial pressures that were 25-fold lower than those of hydrogen that can be metabolized by pure cultures of sulfate reducers or methanogens. The electron donors for Fe(III) reduction also supported Mn(IV) reduction. The electron donors for Fe(III) and Mn(IV) reduction and the inability of A. putrefaciens to completely oxidize multicarbon substrates to carbon dioxide distinguish A. putrefaciens from GS-15, the only other organism that is known to obtain energy for growth by coupling the oxidation of organic compounds to the reduction of Fe(III) or Mn(IV). The ability of A. putrefaciens to reduce large quantities of Fe(III) and to grow in a defined medium distinguishes it from a Pseudomonas sp., which is the only other known hydrogen-oxidizing, Fe(III)-reducing microorganism. Furthermore, A. putrefaciens is the first organism that is known to grow with hydrogen as the electron donor and Mn(IV) as the electron acceptor and is the first organism that is known to couple the oxidation of formate to the reduction of Fe(III) or Mn(IV). Thus, A. putrefaciens provides a much needed microbial model for key reactions in the oxidation of sediment organic matter coupled to Fe(III) and Mn(IV) reduction.

Intraarterial infusion chemotherapy in salvage of limbs involved with advanced neoplasms.

Partial or complete limb salvage has been achieved in seven patients by the use of basal intraarterial infusion chemotherapy. All had either refused amputation or had been considered unsuitable for it. Results in all cases showed marked tumour regression to a size where local measures were then successful in controlling the disease. Six of the patients are alive and well with no sign of recurrence at periods ranging from four months to six years.

Evaluation of Sauerkraut-Like Products From Direct-Acidification of Cabbage 1.

Direct acidification of cabbage using acetic, citric, glucono-delta-lactone, or lactic acid was evaluated as a means of producing sauerkraut-like products. Direct acidification with citric acid gave the most acceptable product for incorporation into sauerkraut-containing foods, but none of the acids gave freshly-prepared products with sauerkraut-like flavor and odor. Sensory evaluations with laboratory panels showed that citric acid-acidified cabbage and naturally fermented sauerkraut were comparable when cooked with frankfurters or incorporated into a three-bean salad. Crisp texture and absence of strong odors were attributes of directly acidified cabbage that would be desirable for some applications of these products.