CDX2 as a Prognostic Biomarker in Stage II and Stage III Colon Cancer.

Background The identification of high-risk stage II colon cancers is key to the selection of patients who require adjuvant treatment after surgery. Microarray-based multigene-expression signatures derived from stem cells and progenitor cells hold promise, but they are difficult to use in clinical practice. Methods We used a new bioinformatics approach to search for biomarkers of colon epithelial differentiation across gene-expression arrays and then ranked candidate genes according to the availability of clinical-grade diagnostic assays. With the use of subgroup analysis involving independent and retrospective cohorts of patients with stage II or stage III colon cancer, the top candidate gene was tested for its association with disease-free survival and a benefit from adjuvant chemotherapy. Results The transcription factor CDX2 ranked first in our screening test. A group of 87 of 2115 tumor samples (4.1%) lacked CDX2 expression. In the discovery data set, which included 466 patients, the rate of 5-year disease-free survival was lower among the 32 patients (6.9%) with CDX2-negative colon cancers than among the 434 (93.1%) with CDX2-positive colon cancers (hazard ratio for disease recurrence, 3.44; 95% confidence interval [CI], 1.60 to 7.38; P=0.002). In the validation data set, which included 314 patients, the rate of 5-year disease-free survival was lower among the 38 patients (12.1%) with CDX2 protein-negative colon cancers than among the 276 (87.9%) with CDX2 protein-positive colon cancers (hazard ratio, 2.42; 95% CI, 1.36 to 4.29; P=0.003). In both these groups, these findings were independent of the patient's age, sex, and tumor stage and grade. Among patients with stage II cancer, the difference in 5-year disease-free survival was significant both in the discovery data set (49% among 15 patients with CDX2-negative tumors vs. 87% among 191 patients with CDX2-positive tumors, P=0.003) and in the validation data set (51% among 15 patients with CDX2-negative tumors vs. 80% among 106 patients with CDX2-positive tumors, P=0.004). In a pooled database of all patient cohorts, the rate of 5-year disease-free survival was higher among 23 patients with stage II CDX2-negative tumors who were treated with adjuvant chemotherapy than among 25 who were not treated with adjuvant chemotherapy (91% vs. 56%, P=0.006). Conclusions Lack of CDX2 expression identified a subgroup of patients with high-risk stage II colon cancer who appeared to benefit from adjuvant chemotherapy. (Funded by the National Comprehensive Cancer Network, the National Institutes of Health, and others.).

Integrating Musculoskeletal Education and Patient Care at Medical Student-Run Free Clinics.

BACKGROUND: Student-run free clinics (SRFCs) have emerged as an important educational component of United States (U.S.) medical schools. Despite the prevalence of musculoskeletal (MSK) problems presenting to SRFCs, students and clinics are often unprepared to diagnose and to treat common MSK complaints. OBJECTIVE: We sought to determine the scope of diagnosis and treatment at a medical student-run free clinic specializing in musculoskeletal care using physical medicine and rehabilitation (PM&R) residents. Secondary goals included reviewing student satisfaction and determining the appropriateness of the clinic in medical education. DESIGN: Retrospective chart review, anonymous online survey. SETTING: Primary care, free student clinic affiliated with tertiary academic medical center. PARTICIPANTS: A total of 20 medical student volunteers, 6 PM&R residents, and 91 community patients. METHODS: We established a musculoskeletal clinic as a specialty referral clinic for the 2 primary care SRFCs with institutional support from a partner medical school. We then reviewed clinical operations retrospectively using electronic medical records and student satisfaction based on an online survey. MAIN OUTCOME MEASUREMENTS: We analyzed patient demographics and chief complaints, referrals provided, and medical services rendered. We also used a 5-point Likert scale to assess student satisfaction. RESULTS: A monthly musculoskeletal referral clinic was established with the oversight of PM&R attendings and residents. The clinic received 91 referrals and managed 61 unique patients over a 2.5-year study period. The most common presentations to the clinic involved knee pain (n = 17, 27.9%) and back pain (n = 16, 26.2%). Pro bono relationships with community and institutional partners enabled all patients to receive medical examinations, physical therapy visits, plain film radiographs, and insurance consultations free of charge. Student satisfaction with teaching and patient care was high, with 19 of 20 students reporting their experience as "good" or "excellent." CONCLUSIONS: SRFCs represent an underused opportunity to enhance MSK education among medical students by treating a variety of common MSK complaints in an underserved population. LEVEL OF EVIDENCE: Not applicable.