Lived experiences of persons with disabilities living with HIV in accessing HIV services in Africa: a qualitative systematic review.

PURPOSE: This qualitative review applies an intersectional lens to explore the lived experiences of persons with disabilities (PWDs) living with human immunodeficiency virus (HIV) in accessing HIV services. METHODS: Using thematic analysis, the intersections relating to HIV, disability, gender, stigma, and poverty were explored. RESULTS: Three themes were identified from the analysis: (1) intersection of gender, HIV, and disability - "For a man, it is easier because we women have a lot to take care of at the home and would not have enough time to go get services"; (2) intersection of stigma, HIV, and disability - "…Look at that one. He's disabled, at the same time HIV-positive. He doesn't even feel sorry for himself … to die quietly at home"; (3) intersection of poverty, HIV, and disability - "…maybe you don't even have money to buy food and if you're on medication you need to eat frequently". The findings highlighted how stigma, poverty, and gender collide in a hierarchy of identities to impede accessibility to HIV services. CONCLUSIONS: Researchers and programme implementers should note the intersecting issues of marginalisation that influence inequities in access to HIV services for PWDs living with HIV. National Strategic Plans should address these specific barriers to ensure accessibility for this marginalised population.Implications for rehabilitationGovernments within Africa should commit to including persons with disabilities (PWDs) living with human immunodeficiency virus (HIV) in National Strategic Plans (NSPs), which will support disability-inclusive HIV programming. The development process of NSPs should also include PWDs living with HIV.The inaccessibility of HIV services for PWDs living with HIV is multifaceted and intersectional. Interventions that consider the different social identities such as gender and socioeconomic status of PWDs living with HIV may be more impactful.Understanding the specific dimensions of access that impacted both the demand and supply side will facilitate efficient HIV programming for PWDs living with HIV.

Ear mite infection restructures otic microbial networks in conservation-reliant Santa Catalina Island foxes (Urocyon littoralis catalinae).

Ceruminous gland tumours are highly prevalent in the ear canals of Santa Catalina Island foxes (Urocyon littoralis catalinae). Previous work suggests that tumours may result from a combination of ectoparasites, disruption of the host-associated microbiome, and host immunopathology. More specifically, ear mite infection has been associated with broad-scale microbial dysbiosis marked by secondary bacterial infection with the opportunistic pathogen Staphylococcus pseudintermedius. Together, ear mites and S. pseudintermedius probably sustain chronic inflammation and promote conditions suitable for tumour development. In the present study, we expanded upon this framework by constructing otic microbial community networks for mite-infected and uninfected foxes sampled in 2017-2019. Across sampling years, we observed consistent signatures of microbial dysbiosis in mite-infected ear canals, including reduced microbial diversity and shifted abundance towards S. pseudintermedius. Network analysis further revealed that mite infection disrupts overall community structure. In mite-infected networks, interaction strengths between taxa were generally weaker, and numerous subnetworks disappeared altogether. We also found that two strains of S. pseudintermedius connected to the main network, suggesting that multistrain biofilm formation may be occurring. In contrast, S. pseudintermedius is peripheral in the uninfected network, with its only connections including a second strain of S. pseudintermedius and the possible competitor Acinetobacter rhizosphaerae. Finally, the lineup of potential keystone taxa shifted across disease states. Fusobacteria spp., a carcinogenesis-promoting microbe, assumed a keystone role in the mite-infected community. Considered together, these findings provide insights into how mite infection may destabilize the microbiome and ultimately contribute to tumour development in this island endemic species.

Genomic Assessment of Cancer Susceptibility in the Threatened Catalina Island Fox (Urocyon littoralis catalinae).

Small effective population sizes raise the probability of extinction by increasing the frequency of potentially deleterious alleles and reducing fitness. However, the extent to which cancers play a role in the fitness reduction of genetically depauperate wildlife populations is unknown. Santa Catalina island foxes (Urocyon littoralis catalinae) sampled in 2007-2008 have a high prevalence of ceruminous gland tumors, which was not detected in the population prior to a recent bottleneck caused by a canine distemper epidemic. The disease appears to be associated with inflammation from chronic ear mite (Otodectes) infections and secondary elevated levels of Staphyloccus pseudointermedius bacterial infections. However, no other environmental factors to date have been found to be associated with elevated cancer risk in this population. Here, we used whole genome sequencing of the case and control individuals from two islands to identify candidate loci associated with cancer based on genetic divergence, nucleotide diversity, allele frequency spectrum, and runs of homozygosity. We identified several candidate loci based on genomic signatures and putative gene functions, suggesting that cancer susceptibility in this population may be polygenic. Due to the efforts of a recovery program and weak fitness effects of late-onset disease, the population size has increased, which may allow selection to be more effective in removing these presumably slightly deleterious alleles. Long-term monitoring of the disease alleles, as well as overall genetic diversity, will provide crucial information for the long-term persistence of this threatened population.

Chromosome-specific KASP markers for detecting Amblyopyrum muticum segments in wheat introgression lines.

Many wild-relative species are being used in prebreeding programs to increase the genetic diversity of wheat (Triticum aestivum L.). Genotyping tools such as single nucleotide polymorphism (SNP)-based arrays and molecular markers have been widely used to characterize wheat-wild relative introgression lines. However, due to the polyploid nature of the recipient wheat genome, it is difficult to develop SNP-based Kompetitive allele-specific polymerase chain reaction (KASP) markers that are codominant to track the introgressions from the wild species. Previous attempts to develop KASP markers have involved both exome- and polymerase chain reaction (PCR)-amplicon-based sequencing of the wild species. But chromosome-specific KASP assays have been hindered by homoeologous SNPs within the wheat genome. This study involved whole genome sequencing of the diploid wheat wild relative Amblyopyrum muticum (Boiss.) Eig and development of a de novo SNP discovery pipeline that generated ∼38,000 SNPs in unique wheat genome sequences. New assays were designed to increase the density of Am. muticum polymorphic KASP markers. With a goal of one marker per 60 Mbp, 335 new KASP assays were validated as diagnostic for Am. muticum in a wheat background. Together with assays validated in previous studies, 498 well distributed chromosome-specific markers were used to recharacterize previously genotyped wheat-Am. muticum doubled haploid (DH) introgression lines. The chromosome-specific nature of the KASP markers allowed clarification of which wheat chromosomes were involved with recombination events or substituted with Am. muticum chromosomes and the higher density of markers allowed detection of new small introgressions in these DH lines.

A roadmap for gene functional characterisation in crops with large genomes: Lessons from polyploid wheat.

Understanding the function of genes within staple crops will accelerate crop improvement by allowing targeted breeding approaches. Despite their importance, a lack of genomic information and resources has hindered the functional characterisation of genes in major crops. The recent release of high-quality reference sequences for these crops underpins a suite of genetic and genomic resources that support basic research and breeding. For wheat, these include gene model annotations, expression atlases and gene networks that provide information about putative function. Sequenced mutant populations, improved transformation protocols and structured natural populations provide rapid methods to study gene function directly. We highlight a case study exemplifying how to integrate these resources. This review provides a helpful guide for plant scientists, especially those expanding into crop research, to capitalise on the discoveries made in Arabidopsis and other plants. This will accelerate the improvement of crops of vital importance for food and nutrition security.

Rapid identification of homozygosity and site of wild relative introgressions in wheat through chromosome-specific KASP genotyping assays.

For future food security, it is important that wheat, one of the most widely consumed crops in the world, can survive the threat of abiotic and biotic stresses. New genetic variation is currently being introduced into wheat through introgressions from its wild relatives. For trait discovery, it is necessary that each introgression is homozygous and hence stable. Breeding programmes rely on efficient genotyping platforms for marker-assisted selection (MAS). Recently, single nucleotide polymorphism (SNP)-based markers have been made available on high-throughput Axiom® SNP genotyping arrays. However, these arrays are inflexible in their design and sample numbers, making their use unsuitable for long-term MAS. SNPs can potentially be converted into Kompetitive allele-specific PCR (KASP™) assays that are comparatively cost-effective and efficient for low-density genotyping of introgression lines. However, due to the polyploid nature of wheat, KASP assays for homoeologous SNPs can have difficulty in distinguishing between heterozygous and homozygous hybrid lines in a backcross population. To identify co-dominant SNPs, that can differentiate between heterozygotes and homozygotes, we PCR-amplified and sequenced genomic DNA from potential single-copy regions of the wheat genome and compared them to orthologous copies from different wild relatives. A panel of 620 chromosome-specific KASP assays have been developed that allow rapid detection of wild relative segments and provide information on their homozygosity and site of introgression in the wheat genome. A set of 90 chromosome-nonspecific assays was also produced that can be used for genotyping introgression lines. These multipurpose KASP assays represent a powerful tool for wheat breeders worldwide.

Ear mite infection is associated with altered microbial communities in genetically depauperate Santa Catalina Island foxes (Urocyon littoralis catalinae).

The host-associated microbiome is increasingly recognized as a critical player in health and immunity. Recent studies have shown that disruption of commensal microbial communities can contribute to disease pathogenesis and severity. Santa Catalina Island foxes (Urocyon littoralis catalinae) present a compelling system in which to examine microbial dynamics in wildlife due to their depauperate genomic structure and extremely high prevalence of ceruminous gland tumors. Although the precise cause is yet unknown, infection with ear mites (Otodectes cynotis) has been linked to chronic inflammation, which is associated with abnormal cell growth and tumor development. Given the paucity of genomic variation in these foxes, other dimensions of molecular diversity, such as commensal microbes, may be critical to host response and disease pathology. We characterized the host-associated microbiome across six body sites of Santa Catalina Island foxes, and performed differential abundance testing between healthy and mite-infected ear canals. We found that mite infection was significantly associated with reduced microbial diversity and evenness, with the opportunistic pathogen Staphylococcus pseudintermedius dominating the ear canal community. These results suggest that secondary bacterial infection may contribute to the sustained inflammation associated with tumor development. As the emergence of antibiotic resistant strains remains a concern of the medical, veterinary, and conservation communities, uncovering high relative abundance of S. pseudintermedius provides critical insight into the pathogenesis of this complex system. Through use of culture-independent sequencing techniques, this study contributes to the broader effort of applying a more inclusive understanding of molecular diversity to questions within wildlife disease ecology.

Development and characterisation of interspecific hybrid lines with genome-wide introgressions from Triticum timopheevii in a hexaploid wheat background.

BACKGROUND: Triticum timopheevii (2n = 4x = 28; AtAtGG), is an important source for new genetic variation for wheat improvement with genes for potential disease resistance and salt tolerance. By generating a range of interspecific hybrid lines, T. timopheevii can contribute to wheat's narrow gene-pool and be practically utilised in wheat breeding programmes. Previous studies that have generated such introgression lines between wheat and its wild relatives have been unable to use high-throughput methods to detect the presence of wild relative segments in such lines. RESULTS: A whole genome introgression approach, exploiting homoeologous recombination in the absence of the Ph1 locus, has resulted in the transfer of different chromosome segments from both the At and G genomes of T. timopheevii into wheat. These introgressions have been detected and characterised using single nucleotide polymorphism (SNP) markers present on a high-throughput Axiom® Genotyping Array. The analysis of these interspecific hybrid lines has resulted in the detection of 276 putative unique introgressions from T. timopheevii, thereby allowing the generation of a genetic map of T. timopheevii containing 1582 SNP markers, spread across 14 linkage groups representing each of the seven chromosomes of the At and G genomes of T. timopheevii. The genotyping of the hybrid lines was validated through fluorescence in situ hybridisation (FISH). Comparative analysis of the genetic map of T. timopheevii and the physical map of the hexaploid wheat genome showed that synteny between the two species is highly conserved at the macro-level and confirmed the presence of inter- and intra-genomic translocations within the At and G genomes of T. timopheevii that have been previously only detected through cytological techniques. CONCLUSIONS: In this work, we report a set of SNP markers present on a high-throughput genotyping array, able to detect the presence of T. timopheevii in a hexaploid wheat background making it a potentially valuable tool for marker assisted selection (MAS) in wheat pre-breeding programs. These valuable resources of high-density molecular markers and wheat-T. timopheevii hybrid lines will greatly enhance the work being undertaken for wheat improvement through wild relative introgressions.

B chromosomes are associated with redistribution of genetic recombination towards lower recombination chromosomal regions in perennial ryegrass.

Supernumerary 'B' chromosomes are non-essential components of the genome present in a range of plant and animal species-including many grasses. Within diploid and polyploid ryegrass and fescue species, including the forage grass perennial ryegrass (Lolium perenne L.), the presence of B chromosomes has been reported as influencing both chromosome pairing and chiasma frequencies. In this study, the effects of the presence/absence of B chromosomes on genetic recombination has been investigated through generating DArT (Diversity Arrays Technology) marker genetic maps for six perennial ryegrass diploid populations, the pollen parents of which contained either two B or zero B chromosomes. Through genetic and cytological analyses of these progeny and their parents, we have identified that, while overall cytological estimates of chiasma frequencies were significantly lower in pollen mother cells with two B chromosomes as compared with zero B chromosomes, the recombination frequencies within some marker intervals were actually increased, particularly for marker intervals in lower recombination regions of chromosomes, namely pericentromeric regions. Thus, in perennial ryegrass, the presence of two B chromosomes redistributed patterns of meiotic recombination in pollen mother cells in ways which could increase the range of allelic variation available to plant breeders.

Knowledge Adequacy on Cervical Cancer Among African Refugee and Non-Refugee Women in Brisbane, Australia.

Cervical cancer is a significant public health issue, especially in the developing countries of sub-Saharan Africa. To examine knowledge adequacy on cervical cancer and screening test among African refugee and non-refugee women in Brisbane and further examine whether the level of knowledge vary between refugee and non-refugee women. A cross-sectional survey was conducted among 254 African-born women conveniently sampled from the Brisbane local government area. The outcome measures were knowledge on cervical cancer and Pap smear. In the multivariate logistic regression analysis non-refugees were more likely than refugees to have adequate knowledge about cervical cancer. Also, non-refugee women who were older and educated beyond secondary school, were more likely to have good knowledge about Pap smear test than refugee women. Overall, knowledge level about cervical cancer is limited among the participants and non-refugee women were more likely than refugee women to have good knowledge about cervical cancer and the screening test. These findings may inform the development of health education interventions for the targeted population to improve knowledge and awareness about cervical cancer and the screening guidelines in Australia.

Barriers and facilitators of cervical cancer screening practices among African immigrant women living in Brisbane, Australia.

PURPOSE: To describe barriers and facilitators of cervical screening practices among African immigrant women living in Brisbane, Australia. METHOD: Nineteen African immigrant women (10 refugee and 9 non-refugee) were recruited using convenience sampling. The interviews were conducted with a semi-structured and open-ended questionnaire guide. All the interviews were audio recorded and transcribed verbatim. The data was manually analysed using interpretative thematic analysis. Thematic categories were identified and organised into coherent broader areas. RESULTS: Lack of knowledge about cervical cancer and Pap smear, the absence of warning signs, embarrassment, fear, concern about the gender of the service provider, lack of privacy, cultural and religious beliefs, and healthcare system factors were identified as barriers to screening. The results did not show any major differences between refugee and non-refugee women. Recommendation of the test by health professionals, provision of standardised information on the test, and preferences for female service providers were identified as facilitators of cervical screening. CONCLUSION: There is a need to provide culturally appropriate approaches to cervical screening practices and to enhance cultural competence among health professionals to apply service delivery models that honour group cultures.

A survey of cervical screening among refugee and non-refugee African immigrant women in Brisbane, Australia.

Issue addressed To compare the level of cervical screening uptake between refugee and non-refugee African immigrant women living in Brisbane, Australia, and examine factors associated with Pap smear testing. Methods Cross-sectional survey with a convenience sample of 254 women aged 21-62 years from 22 African countries (144 refugees, 110 non-refugees). Chi-square tests were used to compare the demographic and health-related characteristics between refugee and non-refugee women. Bivariate and multiple logistic regression analyses were used to assess the relationship between the outcome variable (Pap smear testing) and the independent variables. Results Two-thirds of women had used Pap smear services in Australia. Chi-square test analysis established that non-refugee women were significantly more likely to have used Pap smear services than refugee women (73.6% vs 61.8% respectively; P=0.047). Immigration status, however, was not a significant predictor of cervical screening uptake in the multiple regression analyses. The significant predictors for screening uptake in these analyses were work arrangement, parity, healthcare visit, knowledge about Pap smear and perceived susceptibility to cervical cancer. Conclusion Most women relied on opportunistic screening after receiving invitation letters to screen or after visiting health professionals for antenatal or postnatal care. So what? The findings suggest that organised cervical screening programs are not reaching most African immigrant women living in Brisbane. It is incumbent on the public health sector, including healthcare professionals and settlement agencies working with African communities, to develop health promotion strategies that meaningfully engage African immigrant women, including those from refugee backgrounds, to enhance their knowledge about cervical cancer and screening practices.

High-density SNP genotyping array for hexaploid wheat and its secondary and tertiary gene pool.

In wheat, a lack of genetic diversity between breeding lines has been recognized as a significant block to future yield increases. Species belonging to bread wheat's secondary and tertiary gene pools harbour a much greater level of genetic variability, and are an important source of genes to broaden its genetic base. Introgression of novel genes from progenitors and related species has been widely employed to improve the agronomic characteristics of hexaploid wheat, but this approach has been hampered by a lack of markers that can be used to track introduced chromosome segments. Here, we describe the identification of a large number of single nucleotide polymorphisms that can be used to genotype hexaploid wheat and to identify and track introgressions from a variety of sources. We have validated these markers using an ultra-high-density Axiom(®) genotyping array to characterize a range of diploid, tetraploid and hexaploid wheat accessions and wheat relatives. To facilitate the use of these, both the markers and the associated sequence and genotype information have been made available through an interactive web site.

A review of the evidence for occupational exposure risks to novel anticancer agents - A focus on monoclonal antibodies.

INTRODUCTION: Evidence of occupational exposure risks to novel anticancer agents is limited and yet to be formally evaluated from the Australian healthcare perspective. METHODS: From March to September 2013 medical databases, organizational policies, drug monographs, and the World Wide Web were searched for evidence relating to occupational exposure to monoclonal antibodies, fusion proteins, gene therapies, and other unclassified novel anticancer agents. RESULTS: Australian legislation, national and international guidelines, and drug company information excluded novel agents or provided inconsistent risk assessments and safe handling recommendations. Monoclonal antibody guidelines reported conflicting information and were often divergent with available evidence and pharmacologic rationale demonstrating minimal internalisation ability and occupational exposure risk. Despite similar physiochemical, pharmacologic, and internalisation properties to monoclonal antibodies, fusion proteins were included in only a minority of guidelines. Clinical directives for the safe handling of gene therapies and live vaccines were limited, where available focusing on prevention against exposure and cross-contamination. Although mechanistically different, novel small molecule agents (proteasome inhibitors), possess similar physiochemical and internalisation properties to traditional cytotoxic agents warranting cytotoxic classification and handling. CONCLUSION: Novel agents are rapidly emerging into clinical practice, and healthcare personnel have few resources to evaluate risk and provide safety recommendations. Novel agents possess differing physical, molecular and pharmacological profiles compared to traditional cytotoxic anticancer agents. Evaluation of occupational exposure risk should consider both toxicity and internalisation. Evidence-based guidance able to direct safe handling practices for novel anticancer agents across a variety of clinical settings is urgently required.

Ear Mite Removal in the Santa Catalina Island Fox (Urocyon littoralis catalinae): Controlling Risk Factors for Cancer Development.

Ear mites (Otodectes cynotis) and ear canal tumors are highly prevalent among federally endangered Island foxes (Urocyon littoralis catalinae) living on Santa Catalina Island off the coast of Southern California. Since studies began in the 1990s, nearly all foxes examined were found to be infected with ear mites, and ceruminous gland tumors (carcinomas and adenomas) were detected in approximately half of all foxes ≥ 4 years of age. We hypothesized that reduction of ear mite infection would reduce otitis externa and ceruminous gland hyperplasia, a risk factor for tumor development. In this study, we conducted a randomized field trial to assess the impact of acaricide treatment on ear mite prevalence and intensity of infection, otitis externa, ceruminous gland hyperplasia, and mite-specific IgG and IgE antibody levels. Treatment was highly effective at eliminating mites and reducing otitis externa and ceruminous gland hyperplasia, and mite-specific IgG antibody levels were significantly lower among uninfected foxes. Ceruminous gland hyperplasia increased in the chronically infected, untreated foxes during the six month study. Our results provide compelling evidence that acaricide treatment is an effective means of reducing ear mites, and that mite removal in turn reduces ear lesions and mite-specific IgG antibody levels in Santa Catalina Island foxes. This study has advanced our understanding of the underlying pathogenesis which results in ceruminous gland tumors, and has helped inform management decisions that impact species conservation.

Treatment of Refractory Hiccups with Amantadine.

Persistent or intractable hiccups are not uncommon at the end of life, occurring in approximately 4% to 9% of patients, and can cause considerable suffering, including difficulties in eating, drinking, and speaking, insomnia, pain, fatigue, and depression. In palliative practice, the etiology of hiccups is often either unknown or untreatable, and empirical pharmacologic treatment is the norm. Unfortunately, many of the agents reported as effective for hiccups can cause undesirable sedation. The authors describe a patient with end-stage vascular dementia and a 4-year history of idiopathic intractable hiccups who responded dramatically to amantadine, a nonsedating dopamine agonist. The role of dopamine in hiccups is somewhat ambiguous and likely not central to their cause or treatment. Amantadine may be a reasonable option for patients with distressing hiccups who cannot tolerate a sedating agent.

Pathology and Epidemiology of Ceruminous Gland Tumors among Endangered Santa Catalina Island Foxes (Urocyon littoralis catalinae) in the Channel Islands, USA.

In this study, we examined the prevalence, pathology, and epidemiology of tumors in free-ranging island foxes occurring on three islands in the California Channel Islands, USA. We found a remarkably high prevalence of ceruminous gland tumors in endangered foxes (Urocyon littoralis catalinae) occurring on Santa Catalina Island (SCA)--48.9% of the dead foxes examined from 2001-2008 had tumors in their ears, and tumors were found in 52.2% of randomly-selected mature (≥ 4 years) foxes captured in 2007-2008, representing one of the highest prevalences of tumors ever documented in a wildlife population. In contrast, no tumors were detected in foxes from San Nicolas Island or San Clemente Island, although ear mites (Otodectes cynotis), a predisposing factor for ceruminous gland tumors in dogs and cats, were highly prevalent on all three islands. On SCA, otitis externa secondary to ear mite infection was highly correlated with ceruminous gland hyperplasia (CGH), and tumors were significantly associated with the severity of CGH, ceruminous gland dysplasia, and age group (older foxes). We propose a conceptual model for the formation of ceruminous gland tumors in foxes on SCA that is based on persistent, ubiquitous infection with ear mites, and an innate, over exuberant inflammatory and hyperplastic response of SCA foxes to these mites. Foxes on SCA are now opportunistically treated with acaricides in an attempt to reduce mite infections and the morbidity and mortality associated with this highly prevalent tumor.

Phenotyping pipeline reveals major seedling root growth QTL in hexaploid wheat.

Seedling root traits of wheat (Triticum aestivum L.) have been shown to be important for efficient establishment and linked to mature plant traits such as height and yield. A root phenotyping pipeline, consisting of a germination paper-based screen combined with image segmentation and analysis software, was developed and used to characterize seedling traits in 94 doubled haploid progeny derived from a cross between the winter wheat cultivars Rialto and Savannah. Field experiments were conducted to measure mature plant height, grain yield, and nitrogen (N) uptake in three sites over 2 years. In total, 29 quantitative trait loci (QTLs) for seedling root traits were identified. Two QTLs for grain yield and N uptake co-localize with root QTLs on chromosomes 2B and 7D, respectively. Of the 29 root QTLs identified, 11 were found to co-localize on 6D, with four of these achieving highly significant logarithm of odds scores (>20). These results suggest the presence of a major-effect gene regulating seedling root vigour/growth on chromosome 6D.

Use of percutaneous radiofrequency ablation in pulmonary metastases from renal cell carcinoma.

BACKGROUND: Surgical resection of pulmonary metastases from renal cell carcinoma (RCC) has been demonstrated in recent studies to produce good long-term survival outcomes. Radiofrequency ablation (RFA) may offer an alternative treatment option for this group of patients, especially for those who are unable to have surgery. METHODS: Nine patients had a total of 23 pulmonary metastases treated with percutaneous RFA under fluoro-computed tomography (CT) guidance. Patients underwent routine overnight hospitalization and monitoring for other potential complications. CT scans were performed at 1 month after the procedure and at 3-monthly intervals. RESULTS: A total of 25 ablations were performed to 23 pulmonary metastases for our nine patients in 12 RFA sessions. No patient died within 30 days of the procedure. Five of the 12 procedures resulted in a pneumothorax (42%) and 3 required insertion of a Pleurocath. One patient had a bronchopulmonary fistula with an associated small pleural effusion and one patient had pneumonia. Of the 25 ablations, 14 lesions had decreased in size (56%), 1 was stable in size (4%), and 9 had increased in size (36%). One patient had deceased before adequate follow-up. Of the nine patients, two are alive and free of disease (mean survival time of 74 months), two are alive with disease (mean survival time of 16 months), and five have died of disease (mean survival time of 26.2 months). CONCLUSION: RFA offers a treatment alternative for local tumor control, particularly in selected patients with multiple, small lesions who are unsuitable for pulmonary resections.

Radioembolization with selective internal radiation microspheres for neuroendocrine liver metastases.

BACKGROUND: There are limited effective treatment options available and a poor 5-year survival for patients with inoperable neuroendocrine liver metastases (NETLMs). In this study, the authors prospectively assessed the safety and efficacy of treatment with yttrium 90 ((90)Y) radioactive microspheres for patients with unresectable NETLMs. METHODS: Radioactive (90)Y resin microspheres (selective internal radiation [SIR-Spheres]) were administered through a temporarily placed percutaneous hepatic artery catheter concomitantly with a 7-day systemic infusion of 5-fluorouracil to patients with progressive, unresectable NETLMs. Patients were monitored prospectively, and the response to treatment was measured by using cancer markers and tumor size on computed tomography imaging studies. RESULTS: Thirty-four patients (22 men) with a mean age 61 years (range, 32-79 years) who had unresectable NETLMs were treated between December 2003 and December 2005. The mean (+/-standard error) follow-up was 35.2 +/- 3.2 months. The site of the primary neuroendocrine tumor was the bronchus in 1 patient, the medullary thyroid in 2 patients, gastrointestinal in 15 patients, the pancreas in 8 patients, and of unknown origin in 8 patients. The tumors were classified as vipoma (1 tumor), somatostatinoma (1 tumor), glucagonoma (2 tumors), large cell (3 tumors), carcinoid (25 tumors), and of unknown origin (2 tumors). Complications after (90)Y radioembolization included abdominal pain, which was mild to severe; nausea and fever; and lethargy that lasted from 1 week to 1 month. Two patients developed biopsy-proven radiation gastritis, 1 patient developed a duodenal ulcer, and there was 1 early death from liver dysfunction and pneumonia. Subjective changes from recorded baseline hormone symptoms were reported every 3 months. Symptomatic responses were observed in 18 of 33 patients (55%) at 3 months and in 16 of 32 patients (50%) at 6 months. Radiologic liver responses were observed in 50% of patients and included 6 (18%) complete responses and 11 (32%) partial responses, and the mean overall survival was 29.4 +/- 3.4 months). In patients who had evaluable chromogranin A (CgA) marker levels, there was a fall in CgA marker levels after (90)Y radioembolization in 19 patients (26%) at 1 month, in 19 patients (41%) at 3 months, in 15 patients (43%) at 6 months, in 11 patients (42%) at 12 months, in 8 patients (38%) at 24 months, and in 3 patients (46%) at 30 months. CONCLUSIONS: In this open study of 34 patients, the results demonstrated that radioembolization with (90)Y resin microspheres can achieve relatively long-term responses in some patients with nonresectable NETLMs.