Health and lifestyle behaviors in colorectal cancer survivors with and without Lynch syndrome.

Lynch syndrome (LS), a hereditary cancer syndrome, accounts for approximately 3% of colorectal cancers (CRC). Positive health behaviors and surveillance are preventive strategies, but research on whether recommended behavioral guidelines are followed by individuals with LS is limited. Additional health education and promotion could be beneficial to the improved survivorship of CRC survivors. Explore health and lifestyle behaviors in CRC survivors with and without LS. We conducted a case-control study of CRC survivors with and without LS using a mailed questionnaire. Recruitment was conducted via patient registries at The University of Texas MD Anderson Cancer Center (cases n = 33; controls n = 75) and through social media (cases n = 42). CRC survivors with and without LS in our study had substantially lower smoking prevalence (5.5% and 2.7%) compared to national prevalence (18.0%). However, they had higher levels of alcohol consumption (36.8% and 10.3% for male and female LS survivors, respectively, and 35.8% and 22.0% for male and female sporadic survivors, respectively) compared to national prevalence of 13.88% for males and 6.02% for females. Both groups of CRC survivors participate in negative health behaviors that impact survivorship. More research is needed to examine the relationship between personal engagement in preventive behaviors and patient-provider relationships to improve health behaviors and explore strategies for intervention. Additionally, better health education and lifestyle change recommendations would promote and reinforce positive health outcomes in the CRC population and especially in LS survivors.

Molecular characterization of HDAC8 deletions in individuals with atypical Cornelia de Lange syndrome.

Cornelia de Lange syndrome (CdLS) is a rare neurodevelopmental syndrome for which mutations in five causative genes that encode (SMC1A, SMC3, RAD21) or regulate (NIPBL, HDAC8) the cohesin complex, account for ~70% of cases. Herein we report on four female Subjects who were found to carry novel intragenic deletions in HDAC8. In one case, the deletion was found in mosaic state and it was determined to be present in ~38% of blood lymphocytes and in nearly all cells of a buccal sample. All deletions, for which parental blood samples were available, were shown to have arisen de novo. X-chromosome inactivation studies demonstrated marked skewing, suggesting strong selection against the mutated HDAC8 allele. Based on an investigation of the deletion breakpoints, we hypothesize that microhomology-mediated replicative mechanisms may be implicated in the formation of some of these rearrangements. This study broadens the mutational spectrum of HDAC8, provides the first description of a causative HDAC8 somatic mutation and increases the knowledge on possible mutational mechanisms underlying copy number variations in HDAC8. Moreover our findings highlight the clinical utility of considering copy number analysis in HDAC8 as well as the analysis on DNA from more than one tissue as an indispensable part of the routine molecular diagnosis of individuals with CdLS or CdLS-overlapping features.

Experiential Education Builds Student Self-Confidence in Delivering Medication Therapy Management.

To determine the impact of advanced pharmacy practice experiences (APPE) on student self-confidence related to medication therapy management (MTM), fourth-year pharmacy students were surveyed pre/post APPE to: identify exposure to MTM learning opportunities, assess knowledge of the MTM core components, and assess self-confidence performing MTM services. An anonymous electronic questionnaire administered pre/post APPE captured demographics, factors predicted to impact student self-confidence (Grade point average (GPA), work experience, exposure to MTM learning opportunities), MTM knowledge and self-confidence conducting MTM using a 5-point Likert scale (1 = Not at all Confident; 5 = Extremely Confident). Sixty-two students (26% response rate) responded to the pre-APPE questionnaire and n = 44 (18%) to the post-APPE. Over 90% demonstrated MTM knowledge and 68.2% completed MTM learning activities. APPE experiences significantly improved students' overall self-confidence (pre-APPE = 3.27 (0.85 SD), post-APPE = 4.02 (0.88), p < 0.001). Students engaging in MTM learning opportunities had higher self-confidence post-APPE (4.20 (0.71)) vs. those not reporting MTM learning opportunities (3.64 (1.08), p = 0.05). Post-APPE, fewer students reported MTM was patient-centric or anticipated engaging in MTM post-graduation. APPE learning opportunities increased student self-confidence to provide MTM services. However, the reduction in anticipated engagement in MTM post-graduation and reduction in sensing the patient-centric nature of MTM practice, may reveal a gap between practice expectations and reality.

Health-related quality of life in colorectal cancer survivors: are there differences between sporadic and hereditary patients?

PURPOSE: To compare health-related quality of life (HRQoL) in colorectal cancer (CRC) survivors with sporadic CRC to those with hereditary cancer, specifically Lynch syndrome (LS). METHODS: Participants completed a mailed self-administered questionnaire that assessed, among other things, demographics, clinical characteristics, and health-related quality of life. Using a case-case design, CRC survivors with LS or sporadic cancer were matched on age, sex, race/ethnicity, cancer stage, geography, and time since diagnosis. Participants were recruited from patient registries at The University of Texas MD Anderson Cancer Center (MD Anderson) (n = 33 LS; n = 75 sporadic) and through social media (n = 42 LS). The final sample included 71 LS and 74 sporadic CRC survivors. RESULTS: For LS patients, the mean FACT-C HRQoL score was 84.8 (11.9) [Median = 86.0; Interquartile Range-17] compared to sporadic patients mean score of 85.8 (16.7) [Median = 92.0; Interquartile Range-21], which indicates high quality of life for both groups. LS patients and sporadic CRC patients had similar HRQoL mean scores across 7 different HRQoL metrics, with no significant differences between groups. Exploratory regression analyses indicate some differences in known predictors of HRQoL by group despite no bivariate differences. CONCLUSIONS: HRQoL is an important component of survivorship in CRC patients. Given the clinical distinctions between LS and sporadic patients, we expected to find significant differences between these patients. However, the patients' experiences/quality of life does not appear to illustrate such a clear dissimilarity within CRC survivors. Given the limited data in this area, larger studies, ideally with data obtained from multiple sites, is needed to better investigate the alignment between clinical determination and patient experience as well as to explore the relationship between HRQOL, treatment regimens, and health outcomes.

Two novel RAD21 mutations in patients with mild Cornelia de Lange syndrome-like presentation and report of the first familial case.

Cornelia de Lange syndrome (CdLS) is a developmental disorder characterized by limb reduction defects, characteristic facial features and impaired cognitive development. Mutations in the NIPBL gene predominate; however, mutations in other cohesin complex genes have also been implicated, particularly in atypical and mild CdLS cases. Missense mutations and whole gene deletions in RAD21 have been identified in children with growth retardation, minor skeletal anomalies and facial features that overlap findings in individuals with CdLS. We report the first intragenic deletion and frameshift mutations identified in RAD21 in two patients presenting with atypical CdLS. One patient had an in-frame deletion of exon 13, while the second patient had a c.592_593dup frameshift mutation. The first patient presented with developmental delay, hypospadias, inguinal hernia and dysmorphic features while, the second patient presented with developmental delay, characteristic facial features, hirsutism, and hand and feet anomalies, with the first patient being milder than the second. The in-frame deletion mutation was found to be inherited from the mother who had a history of melanoma and other unspecified medical problems. This study expands the spectrum of RAD21 mutations and emphasizes the clinical utility of performing RAD21 mutation analysis in patients presenting with atypical forms of CdLS. Moreover, the variability of clinical presentation within families and low penetrance of mutations as well as the significance of performing molecular genetic testing in mildly affected patients are discussed.