Radiotherapy respiratory motion management in hepatobiliary and pancreatic malignancies: a systematic review of patient factors influencing effectiveness of motion reduction with abdominal compression.

BACKGROUND: The effectiveness of abdominal compression for motion management in hepatobiliary-pancreatic (HPB) radiotherapy has not been systematically evaluated. METHODS & MATERIALS: A systematic review was carried out using PubMed/Medline, Cochrane Library, Web of Science, and CINAHL databases up to 1 July 2021. No date restrictions were applied. Additional searches were carried out using the University of Manchester digital library, Google Scholar and of retrieved papers' reference lists. Studies conducted evaluating respiratory motion utilising imaging with and without abdominal compression in the same patients available in English were included. Studies conducted in healthy volunteers or majority non-HPB sites, not providing descriptive motion statistics or patient characteristics before and after compression in the same patients or published without peer-review were excluded. A narrative synthesis was employed by tabulating retrieved studies and organising chronologically by abdominal compression device type to help identify patterns in the evidence. RESULTS: The inclusion criteria were met by 6 studies with a total of 152 patients. Designs were a mix of retrospective and prospective quantitative designs with chronological, non-randomised recruitment. Abdominal compression reduced craniocaudal respiratory motion in the majority of patients, although in four studies there were increases seen in at least one direction. The influence of patient comorbidities on effectiveness of compression, and/or comfort with compression was not evaluated in any study. CONCLUSION: Abdominal compression may not be appropriate for all patients, and benefit should be weighed with potential increase in motion or discomfort in patients with small initial motion (<5 mm). Patient factors including male sex, and high body mass index (BMI) were found to impact the effectiveness of compression, however with limited evidence. High-quality studies are warranted to fully assess the clinical impact of abdominal compression on treatment outcomes and toxicity prospective in comparison to other motion management strategies.

Radiopaque drug-eluting embolisation beads as fiducial markers for stereotactic liver radiotherapy.

OBJECTIVE: To determine the feasibility of using radiopaque (RO) beads as direct tumour surrogates for image-guided radiotherapy (IGRT) in patients with liver tumours after transarterial chemoembolisation (TACE). METHODS: A novel vandetanib-eluting RO bead was delivered via TACE as part of a first-in-human clinical trial in patients with either hepatocellular carcinoma or liver metastases from colorectal cancer. Following TACE, patients underwent simulated radiotherapy imaging with four-dimensional computed tomography (4D-CT) and cone-beam CT (CBCT) imaging. RO beads were contoured using automated thresholding, and feasibility of matching between the simulated radiotherapy planning dataset (AVE-IP image from 4D data) and CBCT scans assessed. Additional kV, MV, helical CT and CBCT images of RO beads were obtained using an in-house phantom. Stability of RO bead position was assessed by comparing 4D-CT imaging to CT scans taken 6-20 days following TACE. RESULTS: Eight patients were treated and 4D-CT and CBCT images acquired. RO beads were visible on 4D-CT and CBCT images in all cases and matching successfully performed. Differences in centre of mass of RO beads between CBCT and simulated radiotherapy planning scans (AVE-IP dataset) were 2.0 mm mediolaterally, 1.7 mm anteroposteriorally and 3.5 mm craniocaudally. RO beads in the phantom were visible on all imaging modalities assessed. RO bead position remained stable up to 29 days post TACE. CONCLUSION: RO beads are visible on IGRT imaging modalities, showing minimal artefact. They can be used for on-set matching with CBCT and remain stable over time. ADVANCES IN KNOWLEDGE: The role of RO beads as fiducial markers for stereotactic liver radiotherapy is feasible and warrants further exploration as a combination therapy approach.

A decision tool for radiographer-led abdominal image-guided stereotactic ablative body radiotherapy - Experience from a single institution.

A decision tool for radiographer-led image-guided radiotherapy (IGRT) using cone-beam CT (CBCT) for abdominal stereotactic radiotherapy was developed and successfully implemented in a single department. The confidence of 7 therapeutic radiographers when undertaking online CBCT review increased, and the pooled median online match time was reduced by 1 m 8 s. While this may be advantageous for abdominal SABR, further evaluation of this work in a larger cohort is required to validate these results.

Polymorphisms in bovine immune genes and their associations with somatic cell count and milk production in dairy cattle.

BACKGROUND: Mastitis, an inflammation of the mammary gland, is a major source of economic loss on dairy farms. The aim of this study was to quantify the associations between two previously identified polymorphisms in the bovine toll-like receptor 2 (TLR2) and chemokine receptor 1 (CXCR1) genes and mammary health indictor traits in (a) 246 lactating dairy cow contemporaries representing five breeds from one research farm and (b) 848 Holstein-Friesian bulls that represent a large proportion of the Irish dairy germplasm. To expand the study, a further 14 polymorphisms in immune genes were included for association studies in the bull population. RESULTS: TLR4-2021 associated (P < 0.05) with both milk protein and fat percentage in late lactation (P < 0.01) within the cow cohort. No association was observed between this polymorphism and either yield or composition of milk within the bull population. CXCR1-777 significantly associated (P < 0.05) with fat yield in the bull population and tended to associate (P < 0.1) with somatic cell score (SCS) in the cows genotyped. CD14-1908 A allele was found to associate with increased (P < 0.05) milk fat and protein yield and also tended to associate with increased (P < 0.1) milk yield. A SERPINA1 haplotype with superior genetic merit for milk protein yield and milk fat percentage (P < 0.05) was also identified. CONCLUSION: Of the sixteen polymorphisms in seven immune genes genotyped, just CXCR1-777 tended to associate with SCS, albeit only in the on-farm study. The lack of an association between the polymorphisms with SCS in the Holstein-Friesian data set would question the potential importance of these variants in selection for improved mastitis resistance in the Holstein-Friesian cow.

Administration of a live culture of Lactococcus lactis DPC 3147 into the bovine mammary gland stimulates the local host immune response, particularly IL-1beta and IL-8 gene expression.

Mastitis is one of the most costly diseases to the dairy farming industry. Conventional antibiotic therapy is often unsatisfactory for successful treatment of mastitis and alternative treatments are continually under investigation. We have previously demonstrated, in two separate field trials, that a probiotic culture, Lactococcus lactis DPC 3147, was comparable to antibiotic therapy to treat bovine mastitis. To understand the mode of action of this therapeutic, we looked at the detailed immune response of the host to delivery of this live strain directly into the mammary gland of six healthy dairy cows. All animals elicited signs of udder inflammation 7 h post infusion. At this time, clots were visible in the milk of all animals in the investigation. The most pronounced increase in immune gene expression was observed in Interleukin (IL)-1beta and IL-8, with highest expression corresponding to peaks in somatic cell count. Infusion with a live culture of a Lc. lactis leads to a rapid and considerable innate immune response.

Predominance of a bacteriocin-producing Lactobacillus salivarius component of a five-strain probiotic in the porcine ileum and effects on host immune phenotype.

Relative predominance of each of five probiotic strains was investigated in the ileum of weaned pigs, compared with that in feces, when administered in combination at c. 5 x 10(9) CFU day(-1) for 28 days. Probiotic was excreted at 10(6)-10(9) CFU g(-1) feces, while ileal survival ranged from 10(2) to 10(6) CFU g(-1) digesta. In contrast to the feces, where Lactobacillus murinus DPC6002 predominated, the bacteriocin-producing Lactobacillus salivarus DPC6005 dominated over coadministered strains both in the ileum digesta and in mucosa. Probiotic administration did not alter counts of culturable fecal Lactobacillus or Enterobacteriaceae but higher ileal Enterobacteriaceae were observed in the ileal digesta of probiotic-fed pigs (P<0.05). We observed decreased CD25 induction on T cells and monocytes (P<0.01) and decreased CTLA-4 induction (P<0.05) by the mitogen phytohemagglutinin on CD4 T cells from the probiotic group. Probiotic treatment also increased the proportion of CD4+ CD8+ T cells within the peripheral T-cell population and increased ileal IL-8 mRNA expression (P<0.05). In conclusion, superior ileal survival of L. salivarius compared with the other coadministered probiotics may be due to a competitive advantage conferred by its bacteriocin. The findings also suggest that the five-strain combination may function as a probiotic, at least in part, via immunomodulation.

Integron analysis and genetic mapping of antimicrobial resistance genes in Salmonella enterica serotype Typhimurium.

Antimicrobial resistance determinants may be transferred among bacteria via mobile genetic elements including plasmids, transposons, and the more recently explored integrons. Integrons are naturally occurring genetic elements found as part of the Tn21 transposon family or located on various broad host-range plasmids. The fundamental integron structure consists of a 5'-conserved segment (5'-CS) of 1.4-kbp and a 2-kbp 3'-CS. Between these conserved regions are DNA sequences of variable length and molecular complexity. These intervening sequences are known as gene cassettes, and several have now been characterized. Acquisition and dissemination of these genes located within the integron structure, results in an increase in antimicrobial resistance. Three classes of integron structure have been described. Class 1 integrons are of principal importance in clinical isolates. The 5'-CS of class 1 integrons includes an intI 1 gene of 1358 bp, which encodes a specific recombinase, a member of the DNA integrase family. This gene contains the att1 recombination site, required for specifically integrating gene cassettes. Classes 2 and 3 also contain integrase genes (intI 2 and intI 3), with the former showing 40% sequence identity to those of class 1, and the latter showing 61%. All three classes of integrons contain similar gene cassettes from the same families, which suggests the existence of a common pool of gene cassette with cross-specificity between the classes. When the 3'-CS region is examined in detail, it contains several open reading frames (ORFs). These include qacEDelta1, which confers resistance to quaternary ammonium compounds, often associated with antiseptics, along with a sul1 gene expressing resistance to sulphonamide antimicrobial agents. The sul1 gene encodes the enzyme hydopteroate synthase. Transcription of the sul1 gene begins at a promoter located in the 5'-CS. The latter is also responsible for the transcription of the inserted gene cassette(s). Two additional ORFs, ORF-5 and -6, are located toward the distal end of the 3'-CS. The gene product of ORF 5 appears to share some sequence similarity with puromycin acetyltransferase, and this feature suggests a possible role in antimicrobial resistance. A biological function has yet to be ascribed to ORF-6.

Comparison of phenotypic and genotypic characteristics of Salmonella bredeney associated with a poultry-related outbreak of gastroenteritis in Northern Ireland.

OBJECTIVES: To employ a combination of phenotypic and genotypic subspecies typing methods to aid in an epidemiological investigation of an outbreak of Salmonella bredeney involving ten persons. METHODS: Isolates were characterised by employing antibiogram typing, in addition to two genotyping techniques, including pulsed field gel electrophoresis (PFGE), random amplification of polymorphic DNA (RAPD) with two oligonucleotide primers. RESULTS: An outbreak of gastroenteritis associated with S. bredeney (serovar O:4 H:Lv 1,7) occurred in Belfast, Northern Ireland in November 1997. In total, ten cases were confirmed, of which eight had consumed chicken cooked at local butchers and retailed through one of two local bakeries. One of the remaining cases was secondarily infected within her home and the final case had eaten a product other than cooked chicken from one of the bakeries. Food preparation practices were inadequate in one of the bakeries in question and record keeping and possibly cooking procedures were inadequate in the butchers. S. bredeney was isolated from an uncooked chicken supplied to the butchers confirming that improperly cooked chicken was most likely the source of the outbreak. All outbreak clinical isolates were indistinguishable from each other and were similar to the isolate obtained from the uncooked poultry demonstrating that these DNA-based methods were valuable in the molecular characterization of S. bredeney. CONCLUSIONS: This report emphasises the importance and maintenance of an effective hazard analysis critical control point (HACCP) approach to the processing and retailing of foodstuffs containing chicken in order to help eliminate hazards to public health.

Salmonella enterica serotype Bredeney: antimicrobial susceptibility and molecular diversity of isolates from Ireland and Northern Ireland.

Salmonella enterica serotype Bredeney has emerged as the third most commonly identified serotype among human clinical isolates referred to the Irish National Salmonella Reference Laboratory in the years 1998 to 2000. A collection of 112 isolates of S. enterica serotype Bredeney collected during the period 1995 to 1999 from animal, food, and human sources from both Ireland and Northern Ireland were studied. Antimicrobial susceptibility testing, pulsed-field gel electrophoresis (PFGE), and DNA amplification fingerprinting (DAF) were performed on all isolates. Plasmid profiles were examined on a subset of 33 isolates. A high proportion (74%) of isolates were susceptible to all antimicrobial agents tested. Resistance to both sulfonamide and trimethoprim was observed in 21% of isolates, and resistance to multiple (five) antimicrobial agents was observed in a single isolate (0.9%). Eight different PFGE patterns were obtained, with 87% of isolates grouping as PFGE type A. PFGE type A was predominant in animals, food, and humans. There was good overall concordance between the groups identified by PFGE and DAF. Overall results indicate that most S. enterica serotype Bredeney isolates in Ireland and Northern Ireland from animal and human sources are clonally related.