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Biomedical subjects

Robert S Krouse

Publications and source records attributed to Robert S Krouse.

At least 19 recordsLinked to original sources
PubMed2006

Surgical palliation of bowel obstruction.

MBO is a common but difficult problem for surgeons caring for cancer patients. Nonsurgical interventions should be considered in all patients who have MBO, especially in those with limited expected survival time or for whom surgery will have little effect on disease control. Surgical options can be helpful in the setting of MBO, as long as reasonable goals and realistic out-comes are clear. There is no defined algorithm for all patients with MBO, and decision-making is based on reasonable estimates of survival and treatment-related success. Therefore, better prospective data need to be collected for this population of patients. In addition, a randomized prospective trial comparing treatments based on the clinical scenario could help practitioners who care for patients with this condition.

Humans↗
PubMed2006

The VA Ostomy Health-Related Quality of Life Study: objectives, methods, and patient sample.

OBJECTIVE: To present the design and methods of a multisite study of health-related quality of life (HR-QOL) in veterans living with ostomies. RESEARCH DESIGN AND METHODS: Veterans from Tucson, Indianapolis, and Los Angeles VA Medical Centers were surveyed using the validated City of Hope ostomy-specific tool (mCOH-QOL-Ostomy) and the SF-36V. Cases (ostomates) had a major gastrointestinal procedure that required an intestinal stoma, while controls had similar procedures for which an ostomy was not required. Ostomy subjects were recruited for four focus groups in each of two sites divided by ostomy type (colostomy versus ileostomy) and overall mCOH-QOL-Ostomy HR-QOL score (highest versus lowest quartile). The focus groups further evaluated barriers, concerns, and adaptation methods and skills. MAIN OUTCOME MEASURES: This report presents recruitment results, reliability of survey instruments, and demographic characteristics of the sample. RESULTS: The overall response (i.e., recruitment) rate across all sites was 48% and by site was 53%, 57%, and 37%, respectively (p < 0.001). Internal consistency reliability estimates indicated that both instruments remain reliable in this population (Cronbach's alpha for HR-QOL domains/scales: 0.71-0.96). Cases and controls were similar in demographic characteristics. Proportions of minority subjects matched projections from the site patient populations. Subjects with ostomies had significantly longer time since surgery than controls (p < 0.001). Focus groups were comprised of two to six subjects per group and demonstrated racial diversity at the Los Angeles site. CONCLUSIONS: The unique design of our study of VA patients with ostomies is an illustration of a successful mixed methods approach to HR-QOL research. We collected meaningful quantitative and qualitative data that will be used in the development of new approaches to care that will lead to improved functioning and well-being in persons living with ostomies. Subsequent reports will provide the results of this research project.

Aged↗
PubMed2005

MGMT promoter methylation and field defect in sporadic colorectal cancer.

BACKGROUND: Sporadic colorectal cancers often arise from a region of cells characterized by a "field defect" that has not been well defined molecularly. DNA methylation has been proposed as a candidate mediator of this field defect. The DNA repair gene O6-methylguanine-DNA methyltransferase (MGMT) is frequently methylated in colorectal cancer. We hypothesized that MGMT methylation could be one of the mediators of field cancerization in the colon mucosa. METHODS: We studied MGMT promoter methylation by three different bisulfite-based techniques in tumor, adjacent mucosa, and non-adjacent mucosa from 95 colorectal cancer patients and in colon mucosa from 33 subjects with no evidence of cancer. Statistical tests were two-sided. RESULTS: MGMT promoter methylation was present in 46% of the tumors. Patients whose cancer had MGMT promoter methylation also had substantial MGMT promoter methylation in apparently normal adjacent mucosa. This methylation was seen with a quantitative assay in 50% (22/44; 95% confidence interval [CI] = 34% to 65%) of normal samples with MGMT promoter methylation in the adjacent tumors, 6% (3/51; 95% CI = 1% to 16%) of samples without MGMT methylation in adjacent tumors, and 12% (4/33; 95% CI = 3% to 28%) of control samples (P < .001 for comparison between each of the latter two groups and the first group). MGMT methylation was detected with a more sensitive assay in 94%, 34%, and 27% of these samples, respectively (P < .001). In grossly normal colonic mucosa of colon cancer patients, methylation was detected 10 cm away from the tumor in 10 of 13 cases. Tumors with MGMT promoter methylation had a higher rate of G-to-A mutation in the KRAS oncogene than tumors without MGMT promoter methylation (10/42 versus 3/46, P = .03). Using a sensitive mutant allele-specific amplification assay for KRAS mutations, we also found KRAS mutations in 12% (3/25; 95% CI = 2.5% to 31%) of colorectal mucosas with detectable MGMT methylation and 3% (2/64; 95% CI = 0.4% to 11%) of colorectal mucosas without MGMT methylation (P = .13). CONCLUSION: Some colorectal cancers arise from a field defect defined by epigenetic inactivation of MGMT. Detection of this abnormality may ultimately be useful in risk assessment for colorectal cancer.

Biomarkers, Tumor↗
PubMed2004

Surgical management of malignant bowel obstruction.

MBO is a common but difficult problem for surgeons caring for cancer patients. Nonsurgical interventions should be considered in all patients with MBO, especially inpatients with limited survival or for whom surgery will have little effect on disease control. Although there is no algorithm for all patients with MBO, decision-making is based on reasonable expectations of survival and treatment-related success. Surgical options can be helpful in the setting of MBO as long as reasonable goals and realistic outcomes are clear.

Digestive System Surgical Procedures↗
PubMed2003

Association between Cyclooxygenase expression and colorectal adenoma characteristics.

The cyclooxygenase (COX) pathway is important in colorectal carcinogenesis with the majority of cancers overexpressing COX-2; however, the role of COX-2 in the development of colorectal adenomas is less well defined. Accordingly, we analyzed 108 colorectal adenomas for COX-1 and COX-2 transcription in archival formalin-fixed, paraffin-embedded tissue using by real-time PCR and normalized to beta-actin. Neither COX-1 nor COX-2 mRNA expression differed with regard to age or gender of the subject. COX-2 mRNA expression was significantly higher in distal adenomas (2.2 +/- 1.9) compared with proximal (0.7 +/- 0.5) adenomas (P < 0.0001) and in larger (>/=7 mm) compared with smaller (<7 mm) adenomas (2.3 +/- 2.2 and 1.7 +/- 1.3, respectively, P = 0.04). COX-2 expression did not differ significantly in tubular compared with tubulovillous adenomas, although there appeared to be a trend toward higher COX-2 expression in tubulovillous adenomas with increasing villous content. Additionally, there was not a significant difference in either COX-1 or COX-2 based on the degree of dysplasia Therefore, if COX-2 inhibitors work through a COX-2 mechanism, these agents may have differential effects on colorectal adenomas that are distal and larger.

Adenoma↗
PubMed2002

Immunogenicity of a p210(BCR-ABL) fusion domain candidate DNA vaccine targeted to dendritic cells by a recombinant adeno-associated virus vector in vitro.

Chronic myelogenous leukemia (CML) is characterized by a t(9;22) translocation, which results in the expression of chimeric BCR-ABL fusion oncoproteins that are necessary for oncogenesis, unique to the leukemic clones, and represent enticing targets for immunotherapy. As a strategy for the immunotherapy of CML, we constructed a recombinant adeno-associated virus vector encoding the p210(BCR-ABL) b3a2 variant fusion region with flanking sequences (CWRBA) and used it to express the BCR-ABL fusion region within primary human dendritic cells (DCs), the most potent antigen-presenting cells currently known. Peripheral blood mononuclear cells from healthy donors were primed and restimulated in vitro with autologous DCs transduced with purified CWRBA, CWRAP (negative control), or pulsed with a peptide corresponding to the fusion domain (positive control). No specific responses were generated using DCs transduced with CWRAP. In contrast, CWRBA-transduced DCs primed autologous T cells in an antigen-specific, MHC-restricted fashion to levels comparable with the positive control. CWRBA-transduced DCs elicited both cytotoxic CD4+/Th1 and CD8+ responses, although the former were more readily detected in this system. Cytotoxicity against a tumor cell line endogenously expressing the p210(BCR-ABL) b3a2 variant fusion region was also demonstrable. In addition, HLA-DRB5(*)0101+DRA (DR2a) was identified as a new restriction element capable of presenting the b3a2 BCR-ABL fusion region epitope. Thus, the construct developed herein may serve as a candidate vaccine for gene-based antigen-specific immunotherapy of CML and may serve as a paradigm for the use of DCs transduced with recombinant adeno-associated virus vectors encoding multiepitope immunogens for vaccine development.

Amino Acid Sequence↗
PubMed2002

Decision making in palliative surgery.

BACKGROUND: Palliative surgery for advanced cancer patients involves complex decision making. Surgeons with a cancer-focused practice were surveyed to determine the extent to which palliative surgery was currently practiced, to identify ethical dilemmas and barriers they faced in performing palliative surgery, and to evaluate their treatment choices in four different clinical scenarios. STUDY DESIGN: A 110-item survey was devised after extensive review of the palliative care and palliative surgery literature to evaluate current practices and attitudes regarding palliative surgery. Case vignettes were devised to evaluate dinical factors influencing surgeons' selection of treatment for symptomatic patients with advanced malignancy. RESULTS: Survey response rate was 24% (419 of 1,740). Respondents reported 74% of their surgery caseload as cancer related, and 21% of these as palliative. On a scale of 1 (uncommon problem) to 7 (common problem), surgeons reported that the most common ethical dilemmas in palliative surgery were providing patients with honest information without destroying hope (5.6 +/- 1.4) (mean +/- standard deviation), and preserving patient choice (5.0 +/- 1.7). Bound on error of the average frequency estimate for ethical dilemmas, based on response rate, was 0.08. On a scale of 1 (not a barrier) to 7 (a severe barrier), surgeons rated the most severe barriers to optimum use of palliative surgery as limitations of managed care (4.1 +/- 2.0) and referral to surgery by other specialists (3.9 +/- 1.8). Bound on error of the estimate for average severity of barriers, based on response rate, was 0.09. They rated the least severe barriers to palliative surgery as surgeon avoidance of dying patients (3.0 +/- 1.8) and surgery department reluctance to perform palliative surgery (2.6 +/- 1.6). Analysis of surgeons' treatment selection in case vignettes indicated that patient age, aggressiveness of tumor biology, local extent of disease, and severity of patient symptoms were all variables of influence for treatment selection in patients with advanced malignancies. CONCLUSIONS: Palliative surgery involves numerous ethical dilemmas, the most prominent being providing honest information to patients without destroying hope, and complex treatment decision making. We have identified variables of major influence to surgeons in the palliative treatment selection for patients with advanced, solid malignancies. Validation of these variables as meaningful will require future studies focusing on patient outcomes.

Adult↗