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HYPOTHESIS Because of some inconsistencies in the traditional model of human colorectal carcinogenesis, the cancer stem cell (CSC) model was recently proposed, in which tumor results from neoplastic transformation of stem cells, which become CSCs. Identification of CSCs by expression of surface antigens remains a critical issue because no biomarker has been shown to be completely reliable. CD133 and CD44 are commonly used as CSC markers, and correlation of their expression with colorectal cancer (CRC) clinicopathological features and outcomes may be useful. DESIGN Pilot study. SETTING University hospital. PATIENTS Thirty-six consecutive patients with CRC.CD133 and CD44 expression (alone or combined) was determined in nontumor cells and in tumor cells by flow cytometry, which identified viable cells only. MAIN OUTCOME MEASURES Correlation of CD133 and CD44 expression with each other, with other prognostic indicators, and with disease-free survival. RESULTS CD133 and CD44 expression was significantly higher in tumor cells than in nontumor cells, and expression of one did not necessarily correlate with expression of the other. CD133 or CD44 expression alone was variable, while combined CD133/CD44 expression identified a small subset of cells positive for CRC. CD133 or CD44 overexpression was not associated with CRC recurrence; only high frequencies of CD133+/CD44+ cells were a strong indicator of worse disease-free survival and an independent risk factor for CRC recurrence. CONCLUSION Evaluation of combined CD133/CD44 expression could be useful to identify putative colorectal CSCs and tumors with a poor prognosis.

The aim of this study was to assess early and late results of the Dufourmentel procedure in patients with primary and recurrent sacrococcygeal pilonidal disease.

HYPOTHESIS Bowel resection followed by chemotherapy is a better management strategy than immediate chemotherapy in asymptomatic patients with colorectal cancer and unresectable liver-only metastases at presentation. DESIGN Retrospective study. SETTING University hospital. PATIENTS Sixty-five consecutive symptom-free colorectal cancer patients with unresectable synchronous metastases confined to the liver undergoing bowel tumor resection plus systemic chemotherapy (42 patients [resection group]) or chemotherapy first (23 patients [chemotherapy group]). MAIN OUTCOME MEASURES Long-term survival and identification of prognostic indicators of outcome. RESULTS In the resection group, the mean and median overall survival times were shown to be significantly better than those in the chemotherapy group (P = .03). Performance status, basal serum levels of lactic dehydrogenase and alkaline phosphatase, percentage of liver involvement, potentially curative resection of the bowel tumor, and type of treatment (resection vs chemotherapy) were demonstrated to be the only variables significantly correlated with long-term survival. On multivariate analysis, performance status, extent of liver involvement, and type of treatment were shown to be the only covariates independently associated with survival rate. The rate of liver metastasis downstaging with subsequent curative hepatic resection was clearly associated with good performance status, limited liver involvement, and resection of the bowel tumor. CONCLUSIONS Achieving complete cure in asymptomatic colorectal cancer patients with unresectable synchronous liver-only metastases appears to be mostly the result of shrinkage and resection of hepatic metastases. In patients with good performance status and limited liver involvement, bowel tumor resection appears to be the best treatment option for this purpose.Arch Surg. 2008;143(4):352-358--

Background:Postdialytic rebound (PDR) of plasma solutes is a relevant drawback of intermittent hemodialysis, but its pathophysiological process remains undefined. We assessed the independent effects of efficiency and length of dialytic session on PDR of urea, phosphate, and potassium. Methods:Uremic patients were evaluated at the beginning and end of dialysis and after 180 minutes in 2 randomized crossover studies. In study 1, we compared the effect of standard versus higher efficiency acetate-free biofiltration (AFB) while maintaining the same duration of 4 hours. In study 2, we compared the effect of 3- versus 5-hour AFB sessions while maintaining similar efficiency. Results:In study 1, greater Kt/V (1.49 ± 0.20 versus 1.22 ± 0.15; P< 0.0001) was coupled with significant increases in both absolute removal and PDR of urea and phosphate (PDR of urea, +45% versus +29%; PDR of phosphate, +79% versus +52%), but not of potassium. Similarly, in study 2, shortening the AFB session while maintaining similar absolute removal and Kt/V (1.28 ± 0.09 versus 1.31 ± 0.09) significantly increased PDR of urea and phosphate (PDR of urea, +32% versus +19%; PDR of phosphate, +63% versus +36%), but not of potassium. In both studies, greater PDRs of urea and phosphate were associated with estimated greater removal of these solutes per hour. Conclusion:The rate of removal of phosphate and urea is a critical determinant of their PDR; conversely, potassium is not influenced by removal rate, likely because of its marked cell compartmentalization.

Background:Although most patients with moderate chronic kidney disease (CKD) are managed exclusively in primary care (PC), no data on blood pressure (BP) control in this setting are available. We compared hypertension management in patients with CKD followed up in PC and nephrology tertiary care (TC). Methods:We studied hypertensive patients with estimated glomerular filtration rates (eGFRs) of 15 to 60 mL/min/1.73 m2(0.25 to 1.00 mL/s) exclusively followed up for at least 1 year in PC (n = 259) or TC (n = 186). Results:PC compared with TC patients were characterized by older age (73 ± 10 versus 65 ± 14 years; P< 0.0001), greater prevalences of previous cardiovascular events (59% versus 32%; P< 0.0001) and diabetes (36% versus 23%; P= 0.005), and slightly greater eGFRs (37 ± 10 versus 34 ± 11 mL/min/1.73 m2; P= 0.005). They showed higher BP levels (143 ± 15/82 ± 7 versus 136 ± 18/78 ± 11 mm Hg; P< 0.0001), with a lower prevalence of BP target (5.8% [95% confidence interval (CI), 2.9 to 8.6] versus 21.5% [95% CI, 15.6 to 27.4]; P< 0.0001). The risk for not achieving BP target in PC was 2.6 times greater, independently from age, sex, diabetes, and eGFR. Fewer antihypertensive drugs were prescribed in PC (1.9 ± 1.1 versus 2.5 ± 1.1; P< 0.0001). In both groups, inhibitors of the renin-angiotensin system were the most frequently prescribed drugs (84%), followed by diuretics (50%). However, family physicians almost exclusively prescribed hydrochlorothiazide, whereas nephrologists preferentially prescribed furosemide, administered at a higher dose than in PC (47 ± 41 versus 28 ± 21 mg/d; P= 0.004). Conclusion:Control of CKD-related hypertension is significantly worse in PC despite a greater cardiovascular risk. Barriers to optimal BP control likely are represented by a low number of drugs and inadequate diuretic therapy.

Background:It is not known whether physical exercise increases daily proteinuria in patients with proteinuric nephropathies, thus accelerating progression of the renal lesion. This study evaluates the acute effects of physical exercise on proteinuria in young adults with immunoglobulin A (IgA) nephropathy. Methods:Changes induced by intense physical exercise on quantitative and qualitative proteinuria were evaluated in basal conditions and after 10 days of ramipril therapy in 10 patients with IgA nephropathy, normal glomerular filtration rate (GFR), proteinuria between 0.8 and 1.49 g/24 h, and “glomerular” microhematuria before and after the end of a maximal treadmill Bruce test (B-test). The basal study also was performed in 10 age- and sex-matched healthy volunteers. Results:At rest, GFR averaged 141 ± 23 mL/min; it increased by 16.3% ± 3.3% (P< 0.005) and 7.1% ± 1.6% at 60 and 120 minutes after the B-test, respectively. At rest, GFR-corrected proteinuria averaged protein of 0.76 ± 0.21 mg/min/100 mL GFR; it increased to 1.55 ± 0.28 mg/min/100 mL GFR after 60 minutes (P< 0.001) and declined to 0.60 ± 0.11 mg/min/100 mL GFR at 120 minutes after the end of the B-test. The pattern of urinary proteins remained unchanged, as did microhematuria. Daily proteinuria was not different from the basal value on the day of the B-test. After ramipril therapy, patients showed a reduction in GFR, but no change in daily GFR-corrected proteinuria, pattern of urinary proteins, or hematuria. Conclusion:The increase in proteinuria after exercise in our patients is significant and is not prevented by ramipril therapy, but lasts less than 120 minutes. Therefore, it cannot modify daily proteinuria. Thus, these data do not support the need to reduce acute physical activity in patients with nonnephrotic renal diseases.

AbstractBackground: It is unknown whether chronic erythropoietin (EPO) treatment is able to normalize hemoglobin (Hb) levels and ameliorate cardiac remodeling avoiding blood transfusions in uremic blood transfusion-dependent patients with β-thalassemia minor (β-thal). Methods: In 12 hemodialysis (HD) patients with β-thal, requiring blood transfusions despite EPO therapy, we planned to increase Hb levels up to the target levels (11–12 g/dl) within a one-year period by administering progressively higher doses of EPO (correction phase). We also planned to maintain the Hb target for an additional year (maintenance phase). Results: In the year before the study, patients required 3.3 ± 0.9 units of packed red blood cells. At baseline, the Hb level obtained with an EPO dose of 212 ± 73 U/kg/week i.v. was 8.2 ± 0.8 g/dl. The EPO dose was gradually increased within the first year up to 458 ± 78 U/kg/week at month 12 (correction phase) and then significantly tapered down during the maintenance phase (390 ± 54 U/kg/week at month 24). During the correction phase, the Hb levels markedly increased (11.1 ± 0.3 g/dl at month 12) and did not change in the maintenance phase. No blood transfusion was required throughout the 2 years of follow-up. Left ventricular (LV) mass index progressively decreased from the basal value of 144 ± 12 to 124 ± 11 g/m2 in the first year and normalized in all patients at month 24 (109 ± 12 g/m2, p &lt; 0.001); this occurred in the absence of any change of LV cavity volume index (&lt;90 ml/m2). Conclusions: In HD transfusion-dependent patients with β-thal, the administration of high EPO dose for 2 years permits the attainment and the maintenance of Hb targets without blood transfusions. This therapeutic approach permits a complete remission of concentric LV hypertrophy without any adverse effects on the vascular system.Copyright © 2004 S. Karger AG, Basel

Background:It is unknown whether chronic erythropoietin (EPO) treatment is able to normalize hemoglobin (Hb) levels and ameliorate cardiac remodeling avoiding blood transfusions in uremic blood transfusion-dependent patients with β-thalassemia minor (β-thal). Methods:In 12 hemodialysis (HD) patients with β-thal, requiring blood transfusions despite EPO therapy, we planned to increase Hb levels up to the target levels (11–12 g/dl) within a one-year period by administering progressively higher doses of EPO (correction phase). We also planned to maintain the Hb target for an additional year (maintenance phase). Results:In the year before the study, patients required 3.3 ± 0.9 units of packed red blood cells. At baseline, the Hb level obtained with an EPO dose of 212 ± 73 U/kg/week i.v. was 8.2 ± 0.8 g/dl. The EPO dose was gradually increased within the first year up to 458 ± 78 U/kg/week at month 12 (correction phase) and then significantly tapered down during the maintenance phase (390 ± 54 U/kg/week at month 24). During the correction phase, the Hb levels markedly increased (11.1 ± 0.3 g/dl at month 12) and did not change in the maintenance phase. No blood transfusion was required throughout the 2 years of follow-up. Left ventricular (LV) mass index progressively decreased from the basal value of 144 ± 12 to 124 ± 11 g/m2 in the first year and normalized in all patients at month 24 (109 ± 12 g/m2, p < 0.001); this occurred in the absence of any change of LV cavity volume index (<90 ml/m2). Conclusions:In HD transfusion-dependent patients with β-thal, the administration of high EPO dose for 2 years permits the attainment and the maintenance of Hb targets without blood transfusions. This therapeutic approach permits a complete remission of concentric LV hypertrophy without any adverse effects on the vascular system.