Management of Dyspnea in Advanced Cancer: ASCO Guideline.

PURPOSE To provide guidance on the clinical management of dyspnea in adult patients with advanced cancer. METHODS ASCO convened an Expert Panel to review the evidence and formulate recommendations. An Agency for Healthcare Research and Quality (AHRQ) systematic review provided the evidence base for nonpharmacologic and pharmacologic interventions to alleviate dyspnea. The review included randomized controlled trials (RCTs) and observational studies with a concurrent comparison group published through early May 2020. The ASCO Expert Panel also wished to address dyspnea assessment, management of underlying conditions, and palliative care referrals, and for these questions, an additional systematic review identified RCTs, systematic reviews, and guidelines published through July 2020. RESULTS The AHRQ systematic review included 48 RCTs and two retrospective cohort studies. Lung cancer and mesothelioma were the most commonly addressed types of cancer. Nonpharmacologic interventions such as fans provided some relief from breathlessness. Support for pharmacologic interventions was limited. A meta-analysis of specialty breathlessness services reported improvements in distress because of dyspnea. RECOMMENDATIONS A hierarchical approach to dyspnea management is recommended, beginning with dyspnea assessment, ascertainment and management of potentially reversible causes, and referral to an interdisciplinary palliative care team. Nonpharmacologic interventions that may be offered to relieve dyspnea include airflow interventions (eg, a fan directed at the cheek), standard supplemental oxygen for patients with hypoxemia, and other psychoeducational, self-management, or complementary approaches. For patients who derive inadequate relief from nonpharmacologic interventions, systemic opioids should be offered. Other pharmacologic interventions, such as corticosteroids and benzodiazepines, are also discussed

Expression of HIWI in human esophageal squamous cell carcinoma is significantly associated with poorer prognosis

<p>Abstract</p> <p>Background</p> <p>HIWI, the human homologue of Piwi family, is present in CD34⁺hematopoietic stem cells and germ cells, but not in well-differentiated cell populations, indicating that HIWI may play an impotent role in determining or maintaining stemness of these cells. That HIWI expression has been detected in several type tumours may suggest its association with clinical outcome in cancer patients.</p> <p>Methods</p> <p>With the methods of real-time PCR, western blot, immunocytochemistry and immunohistochemistry, the expression of HIWI in three esophageal squamous cancer cell lines KYSE70, KYSE140 and KYSE450 has been characterized. Then, we investigated HIWI expression in a series of 153 esophageal squamous cell carcinomas using immunohistochemistry and explored its association with clinicopathological features.</p> <p>Results</p> <p>The expression of HIWI was observed in tumour cell nuclei or/and cytoplasm in 137 (89.5%) cases, 16 (10.5%) cases were negative in both nuclei and cytoplasm. 86 (56.2%) were strongly positive in cytoplasm, while 49 (32.0%) were strongly positive in nuclei. The expression level of HIWI in cytoplasm of esophageal cancer cells was significantly associated with histological grade (<it>P </it>= 0.011), T stage (<it>P </it>= 0.035), and clinic outcome (<it>P </it>< 0.001), while there was no correlation between the nuclear HIWI expression and clinicopathological features.</p> <p>Conclusion</p> <p>The expression of HIWI in the cytoplasm of esophageal cancer cells is significantly associated with higher histological grade, clinical stage and poorer clinical outcome, indicating its possible involvement in cancer development.</p

The transition experience of rural older persons with advanced cancer and their families: a grounded theory study

BACKGROUND: Transitions often occur suddenly and can be traumatic to both patients with advanced disease and their families. The purpose of this study was to explore the transition experience of older rural persons with advanced cancer and their families from the perspective of palliative home care patients, bereaved family caregivers, and health care professionals. The specific aims were to: (1) describe the experience of significant transitions experienced by older rural persons who were receiving palliative home care and their families and (2) develop a substantive theory of transitions in this population. METHODS: Using a grounded theory approach, 27 open-ended individual audio-taped interviews were conducted with six older rural persons with advanced cancer and 10 bereaved family caregivers. Four focus group interviews were conducted with 12 palliative care health care professionals. All interviews were transcribed verbatim, coded, and analyzed using Charmaz\u27s constructivist grounded theory approach. RESULTS: Within a rural context of isolation, lack of information and limited accessibility to services, and values of individuality and community connectedness, older rural palliative patients and their families experienced multiple complex transitions in environment, roles/relationships, activities of daily living, and physical and mental health. Transitions disrupted the lives of palliative patients and their caregivers, resulting in distress and uncertainty. Rural palliative patients and their families adapted to transitions through the processes of Navigating Unknown Waters . This tentative theory includes processes of coming to terms with their situation, connecting, and redefining normal. Timely communication, provision of information and support networks facilitated the processes. CONCLUSION: The emerging theory provides a foundation for future research. Significant transitions identified in this study may serve as a focus for improving delivery of palliative and end of life care in rural areas. Improved understanding of the transitions experienced by advanced cancer palliative care patients and their families, as well as the psychological processes involved in adapting to the transitions, will help health care providers address the unique needs of this vulnerable population

Alternative Splicing Regulation During C. elegans Development: Splicing Factors as Regulated Targets

Alternative splicing generates protein diversity and allows for post-transcriptional gene regulation. Estimates suggest that 10% of the genes in Caenorhabditis elegans undergo alternative splicing. We constructed a splicing-sensitive microarray to detect alternative splicing for 352 cassette exons and tested for changes in alternative splicing of these genes during development. We found that the microarray data predicted that 62/352 (∼18%) of the alternative splicing events studied show a strong change in the relative levels of the spliced isoforms (>4-fold) during development. Confirmation of the microarray data by RT-PCR was obtained for 70% of randomly selected genes tested. Among the genes with the most developmentally regulated alternatively splicing was the hnRNP F/H splicing factor homolog, W02D3.11 – now named hrpf-1. For the cassette exon of hrpf-1, the inclusion isoform comprises 65% of hrpf-1 steady state messages in embryos but only 0.1% in the first larval stage. This dramatic change in the alternative splicing of an alternative splicing factor suggests a complex cascade of splicing regulation during development. We analyzed splicing in embryos from a strain with a mutation in the splicing factor sym-2, another hnRNP F/H homolog. We found that approximately half of the genes with large alternative splicing changes between the embryo and L1 stages are regulated by sym-2 in embryos. An analysis of the role of nonsense-mediated decay in regulating steady-state alternative mRNA isoforms was performed. We found that 8% of the 352 events studied have alternative isoforms whose relative steady-state levels in embryos change more than 4-fold in a nonsense-mediated decay mutant, including hrpf-1. Strikingly, 53% of these alternative splicing events that are affected by NMD in our experiment are not obvious substrates for NMD based on the presence of premature termination codons. This suggests that the targeting of splicing factors by NMD may have downstream effects on alternative splicing regulation