Use of molecular tumor characteristics to prioritize mismatch repair gene testing in early-onset colorectal cancer.

PURPOSE: The relationships between mismatch repair (MMR) protein expression, microsatellite instability (MSI), family history, and germline MMR gene mutation status have not been studied on a population basis. METHODS: We studied 131 unselected patients with colorectal cancer diagnosed younger than age 45 years. For the 105 available tumors, MLH1, MSH2, MSH6, and PMS2 protein expression using immunohistochemistry (IHC) and MSI were measured. Germline DNA was screened for hMLH1, hMSH2, hMSH6, and hPMS2 mutations for the following patients: all from families fulfilling the Amsterdam Criteria for hereditary nonpolyposis colorectal cancer (HNPCC); all with tumors that were high MSI, low MSI, or that lacked expression of any MMR protein; and a random sample of 23 with MS-stable tumors expressing all MMR proteins. RESULTS: Germline mutations were found in 18 patients (nine hMLH1, four hMSH2, four hMSH6, and one hPMS2); all tumors exhibited loss of MMR protein expression, all but one were high MSI or low MSI, and nine were from a family fulfilling Amsterdam Criteria. Sensitivities of IHC testing, MSI (high or low), and Amsterdam Criteria for MMR gene mutation were 100%, 94%, and 50%, respectively. Corresponding positive predictive values were 69%, 50%, and 75%. CONCLUSIONS: Tumor IHC analysis of four MMR proteins and MSI testing provide a highly sensitive strategy for identifying MMR gene mutation-carrying, early-onset colorectal cancer patients, half of whom would have been missed using Amsterdam Criteria alone. Tumor-based approaches for triaging early-onset colorectal cancer patients for MMR gene mutation testing, irrespective of family history, appear to be an efficient screening strategy for HNPCC.     

Elevation of cerebrospinal fluid soluble CD27 levels in patients with meningeal localization of lymphoid malignancies [published erratum appears in Blood 1996 Oct 1;88(7):2818]

Diagnosis of meningeal localization of lymphoid malignancies by means of cytologic examination of the cerebrospinal fluid (CSF) can be difficult. Thus far no reliable CSF tumor markers have been identified. CD27 is a transmembrane disulfide-linked 55-kD homodimer present on most peripheral blood T cells and on a subset of B cells. CD27 is also expressed on human malignant B cells and high levels of soluble CD27 can be present in the serum of patients with B-cell malignancies. The aim of this study is to determine prospectively the diagnostic value of CSF sCD27 as a tumor marker in patients with meningeal localization of lymphoid malignancies. CSF sCD27 levels were determined by sandwich enzyme-linked immunosorbent assay. The optimal cut-off value using receiver operator characteristics curves was found to be 10 U/mL. sCD27 levels were normal in all 50 control patients (lumbar disc protrusion) and in 39 of 40 samples obtained from patients with either solid tumors or acute myeloid leukemia. Of 104 CSF samples from 70 children with acute lymphoblastic leukemia (ALL) or non-Hodgkin's lymphoma (NHL) undergoing routine central nervous system (CNS) staging, sCD27 was false positive and false negative in only one sample each. In 70 samples from 45 patients suspected of meningeal localization of ALL or NHL, the sCD27 test had an excellent sensitivity (100%) and specificity (82%). In 7 patients with positive CSF studied longitudinally, sCD27 levels correlated very well with remission and relapse. sCD27 levels were not nonspecifically increased by the administration of cytostatic drugs. Finally, sCD27 was also elevated in the 4 patients studied with primary central nervous system lymphoma (PCNSL). CSF sCD27 is a promising tumor marker in patients with either meningeal localization of lymphoid malignancies or PCNSL, and can be useful in the differential diagnosis of CNS involvement by either lymphoid malignancies or solid tumors.     

Myometrial invasion by endometrial carcinoma: sonographic assessment

The depth of myometrial invasion by endometrial carcinoma was evaluated using real-time sonography (US) in 20 patients with histologically proved adenocarcinoma of the endometrium. In 14 of 20 (70%) cases, US-based estimation of the depth of myometrial invasion was within 10% of the actual measurement in the gross specimen. The US-based estimation of tumor invasion was low in seven patients, high in four patients, and agreed with pathologic findings (+/- 5%) in nine patients. In four patients with polypoid intraluminal extension of tumor, a deeply invasive tumor was suspected on US but was not found on pathologic examination. In 12 superficially invasive tumors, the continuity of the demarcating subendometrial halo was intact in nine and incomplete in three. In six patients with deeply invasive tumors, this zone was partially disrupted in four, totally disrupted in one, and intact in one. Errors of estimation of the depth of myometrial invasion on US most frequently occurred when a tumor had a significant intraluminal polypoid extension. Demonstration of a subendometrial halo usually indicated superficial invasion, whereas the absence of a halo was frequently associated with deep invasion.     

What's driving an epidemic? The spread of syphilis along an interstate highway in rural North Carolina.

OBJECTIVES: The purpose of this study was to determine whether county syphilis rates were increased along Interstate Highway 95 (I-95) in North Carolina during a recent epidemic. METHODS: Ecological data on syphilis cases demographic data, highway data, and drug activity data were used to conduct a cross-sectional and longitudinal study of North Carolina countries from 1985 to 1994. Crude and adjusted incidence rate ratios (IRRs) were determined by means of standard and longitudinal Poisson regression models adjusted for sociodemographic factors and drug use. RESULTS: Ten-year syphilis rates in I-95 counties greatly exceeded rates in non-I-95 counties (38 vs 16 cases per 100,000 persons) and remained higher after adjustment for race, age, sex, poverty, large cities, and drug activity (adjusted IRR = 2.05, 95% confidence interval [CI] = 1.84, 2.28). Syphilis rates were stable until 1989, when rates increased sharply in I-95 counties but remained stable in non-I-95 counties. Increased drug activity in I-95 counties preceded the rise in syphilis cases. CONCLUSIONS: A better understanding of the relationship between high-ways and the spread of sexually transmitted diseases may guide future prevention interventions.     

Endoscopic Duodenal–Jejunal Bypass Liner Rapidly Improves Type 2 Diabetes

Background

Bariatric procedures excluding the proximal small intestine improve glycemic control in type 2 diabetes within days. To gain insight into the mediators involved, we investigated factors regulating glucose homeostasis in patients with type 2 diabetes treated with the novel endoscopic duodenal–jejunal bypass liner (DJBL).

Methods

Seventeen obese patients (BMI 30–50 kg/m²) with type 2 diabetes received the DJBL for 24 weeks. Body weight and type 2 diabetes parameters, including HbA_1c and plasma levels of glucose, insulin, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and glucagon, were analyzed after a standard meal before, during, and 1 week after DJBL treatment.

Results

At 24 weeks after implantation, patients had lost 12.7?±?1.3 kg (p?<?0.01), while HbA_1c had improved from 8.4?±?0.2 to 7.0?±?0.2 % (p?<?0.01). Both fasting glucose levels and the postprandial glucose response were decreased at 1 week after implantation and remained decreased at 24 weeks (baseline vs. week 1 vs. week 24: 11.6?±?0.5 vs. 9.0?±?0.5 vs. 8.6?±?0.5 mmol/L and 1,999?±?85 vs. 1,536?±?51 vs. 1,538?±?72 mmol/L/min, both p?<?0.01). In parallel, the glucagon response decreased (23,762?±?4,732 vs. 15,989?±?3,193 vs. 13,1207?±?1,946 pg/mL/min, p?<?0.05) and the GLP-1 response increased (4,440?±?249 vs. 6,407?±?480 vs. 6,008?±?429 pmol/L/min, p?<?0.01). The GIP response was decreased at week 24 (baseline—115,272?±?10,971 vs. week 24—88,499?±?10,971 pg/mL/min, p?<?0.05). Insulin levels did not change significantly. Glycemic control was still improved 1 week after explantation.

Conclusions

The data indicate DJBL to be a promising treatment for obesity and type 2 diabetes, causing rapid improvement of glycemic control paralleled by changes in gut hormones.     

Smoking cessation factors among African Americans and whites. COMMIT Research Group.

OBJECTIVES. This study was undertaken to explore smoking patterns and attitudes that influence smoking cessation and relapse among African Americans. METHODS. Baseline data from eight Community Intervention Trial for Smoking Cessation (COMMIT) sites were analyzed. RESULTS. Compared with Whites, African Americans who smoke less than 25 cigarettes per day were 1.6 times more likely to smoke within 10 minutes of awakening (a behavioral indicator of nicotine dependence), adjusting for education, age, and gender (OR = 1.2 for heavier smokers). African Americans reported a stronger desire to quit smoking and reported serious quit attempts in the past year. African Americans favored tobacco restrictions (they were 1.8 times more likely than Whites to view smoking as a serious community problem, 1.7 times more likely to favor restrictions on cigarette vending machines, and 2.1 times more likely to prohibit smoking in their car). African Americans were lighter/moderate, menthol smokers. CONCLUSIONS. African Americans find smoking socially unacceptable and are strongly motivated to quit, but their "wake-up" smoking may indicate high nicotine dependence, making abstinence difficult even for lighter smokers.     

Use of C-Arm Fluoroscopy by Nurses for Placement of PICC Lines

The Minnesota Department of Health Ionizing Radiation Rules “prohibits the use of fluoroscopy by a person other than a licensed practitioner of the healing arts... when the licensed practitioner of the healing arts is not physically present in the room” (Minnesota Administrative Rules, 2007). Getting a licensed practitioner into the room caused delays in completing PICC line insertion procedures. To minimize these delays we considered multiple options; one of the options was to have PICC nurses licensed to operate the fluoroscopy machine. This article will explain the process the Vascular Access Department at the University of Minnesota Medical Center, Fairview went through to make this option a reality.Our team has demonstrated that with proper training, education, machine maintenance and completion of competencies, nurses can operate fluoroscopy independently and clear PICC lines for use with a high degree of safety, efficiency and accuracy.     

The natural history of HIV-1 infection: staging classifications of disease.

We evaluated and compared four staging classification systems for HIV infection in a population-based cohort: (1) a staging based on prodromal clinical criteria; (2) the Walter Reed Staging Classification (WRSC); (3) the immunologic staging system (ISS), and (4) a simple staging based on oral disease and CD4+ T-cell depletion. The staging systems were applied to 386 HIV-infected men in the San Francisco Men's Health Study cohort who did not have AIDS at the baseline examination. After 48-56 months of follow-up the cumulative incidence of AIDS and the cumulative mortality by stage was determined for each staging. Unlike the other systems, the WRSC could not classify a substantial proportion of HIV-infected men (51.9%). The WRSC and ISS include one or more stages which did not appear to be associated with a prognosis substantially different from that of adjacent stages. The simplified staging system based on CD4+ T-cell depletion and oral disease may be the most effective of the systems studied. A more complete understanding of the pathophysiology during the evolution of HIV infection will be required to define a more detailed staging of this disease.