Variation in the Thoroughness of Pathologic Assessment and Response Rates of Locally Advanced Rectal Cancers After Chemoradiation.

BACKGROUND: Pathologic complete response (pCR) is associated with better prognosis and guides management for patients with advanced rectal cancer. Response rates vary between series for unclear reasons. We examine whether the thoroughness of pathologic assessment explains differences in pCR rates. METHODS: We retrospectively reviewed pathology reports from patients with stage II/III rectal cancer who underwent chemoradiation and resection in a prospective, multicenter trial. We utilized a novel measure for the thoroughness of pathologic assessment by dividing residual tumor size by the number of cassettes evaluated (tumor size to cassette ratio, TSCR), and evaluated whether TSCR is associated with pCR. We validated our findings using a separate cohort. RESULTS: From the trial cohort, 71 of 247 (29%) patients achieved pCR. The pCR rate ranged from 0 to 45% and mean TSCR ranged 0.29 to 0.87 across 12 institutions. Within each institution, a lower TSCR was associated with pCR, demonstrating a higher degree of thoroughness used for tumors that achieved pCR. Moreover, across all samples, low TSCR was independently associated with pCR on multivariable analysis. This finding was corroborated in a separate cohort of 201 tumors evaluated by five pathologists; each pathologist had a lower mean TSCR for pCR calls compared with non-pCR calls. However, the mean TSCR for an institution was not associated with its overall pCR rate. CONCLUSIONS: Pathologists assess rectal cancers that have responded significantly to neoadjuvant therapy more thoroughly. Thoroughness does not appear to explain differences in pCR rates between institutions. Our results suggest pCR is not a sampling artifact.

Patient-oriented education and medication management intervention for people with decompensated cirrhosis: study protocol for a randomized controlled trial.

BACKGROUND: People with decompensated cirrhosis require complex medical care and are often prescribed an intricate and frequently changing medication and lifestyle regimen. However, many patients mismanage their medications or have poor comprehension of their disease and self-management tasks. This can lead to harm, hospitalization, and death. METHODS/DESIGN: A patient-oriented education and medication management intervention has been developed for implementation at a tertiary hospital hepatology outpatient center in Queensland, Australia. Consenting patients with decompensated cirrhosis will be randomly allocated to education intervention or usual care treatment arms when they attend routine follow-up appointments. In the usual care arm, participants will be reviewed by their hepatologist according to the current model of care in the hepatology clinic. In the intervention arm, participants will be reviewed by a clinical pharmacist to receive the education and medication management intervention at baseline in addition to review by their hepatologist. Intervention participants will also receive three further educational contacts from the clinical pharmacist within the following 6-month period, in addition to routine hepatologist review that is scheduled within this time frame. All participants will be surveyed at baseline and follow-up (approximately 6 months post-enrollment). Validated questionnaire tools will be used to determine participant adherence, medication beliefs, illness perceptions, and quality of life. Patients' knowledge of dietary and lifestyle modifications, their current medications, and other clinical data will be obtained from the survey, patient interview, and medical records. Patient outcome data will be collected at 52 weeks. DISCUSSION: The intervention described within this protocol is ready to adapt and implement in hepatology ambulatory care centers globally. Investigation of potentially modifiable variables that may impact medication management, in addition to the effect of a clinical pharmacist-driven education and medication management intervention on modifying these variables, will provide valuable information for future management of these patients. TRIAL REGISTRATION: Australian and New Zealand Clinical Trial Registry identifier: ACTRN12616000780459 . Registered on 15 June 2016.

Evolutionary signatures of common human cis-regulatory haplotypes.

Variation in gene expression may give rise to a significant fraction of inter-individual phenotypic variation. Studies searching for the underlying genetic controls for such variation have been conducted in model organisms and humans in recent years. In our previous effort of assessing conserved underlying haplotype patterns across ethnic populations, we constructed common haplotypes using SNPs having conserved linkage disequilibrium (LD) across ethnic populations. These common haplotypes cluster into a simple evolutionary structure based on their frequencies, defining only up to three conserved clusters termed 'haplotype frameworks'. One intriguing preliminary finding was that a significant portion of reported variants strongly associated with cis-regulation tags these globally conserved haplotype frameworks. Here we expand the investigation by collecting genes showing stringently determined cis-association between genotypes and expression phenotypes from major studies. We conducted phylogenetic analysis of current major haplotypes along with the corresponding haplotypes derived from chimpanzee reference sequences. Our analysis reveals that, for the vast majority of such cis-regulatory genes, the tagging SNPs showing the strongest association also tag the haplotype lineages directly separated from ancestry, inferred from either chimpanzee reference sequences or the allele frequency-derived haplotype frameworks, suggesting that the differentially expressed phenotypes were evolved relatively early in human history. Such evolutionary signatures provide keys for a more effective identification of globally-conserved candidate regulatory haplotypes across human genes in future epidemiologic and pharmacogenetic studies.

The surgical treatment of cancer: a comparison of resource utilization following procedures performed with a curative and palliative intent.

BACKGROUND: Costs associated with the provision of medical care continue to escalate. Therefore, providers must evaluate the cost-effectiveness and benefit to individual healthcare practices. The authors evaluated the immediate and short-term resource utilization needs of patients undergoing surgical intervention with curative or palliative intent. METHODS: Three hundred two patients undergoing surgery with therapeutic intent were observed from the time of admission for intervention until the time of death or until 6 months from the time of the surgical procedure. Surgeons preoperatively identified each case as either curative or palliative in intent. Demographic information, as well as the nature of all interactions with the cancer center, was recorded. RESULTS: Surgeons identified 58 (19%) procedures as palliative and 244 (81%) as curative in intent. Demographic characteristics between the two groups were similar, although recurrent or metastatic disease was more often present in palliative rather than curative patients (P = 0.0078) and palliative intent patients were more likely to have received previous therapy. During the 6-month period, 4690 encounters occurred with the cancer center. The mean number of encounters per patient in each group was similar, although curative intent patients were more likely to have visits with therapeutic intent including chemotherapy administration (P = 0.01), radiation (P = 0.003), or repeat surgical procedures (P = 0.006). In contrast, palliative patients were more likely to be admitted for management of symptoms (P = 0.0001) and had fewer hospital-free days than did curative patients (P = 0.0069). CONCLUSIONS: The average number of encounters for patients undergoing treatment of disease was not significantly different, suggesting that patients undergoing surgery with palliative intent do not require a greater amount of resources than curative intent patients. The nature of the interactions, however, was different, suggesting that resource needs are different and may need to be anticipated in the assessment of how better quality outcomes can be achieved in the palliative surgery setting.