Israel Medical Association Journal

Background: Cancer is a leading cause of mortality worldwide. The most effective way to combat cancer is by prevention and early detection.

Objectives: To evaluate the outcome of screening an asymptomatic population for the presence of benign and neoplastic lesions.

Methods: Routine screening tests for prevention and/or early detection of 11 common cancers were conducted in 300 consecutive asymptomatic, apparently healthy adults, aged 25–77 years. Other tests were performed as indicated.

Results: Malignant and benign lesions were found in 3.3% and 5% of the screenees, respectively, compared to 1.7% in the general population. The most common lesions were in the gastrointestinal tract followed by skin, urogenital tract and breast. Advanced age and a family history of a malignancy were associated with increased risk for cancer with an odds ratio of 9 and 3.5, respectively (95% confidence interval 1.1–71 and 0.9–13, respectively). Moreover, high serum C-reactive protein levels and polymorphisms in the APC and CD24 genes indicated high cancer risk. When two of the polymorphisms existed in an individual, the risk for a malignant lesion was extremely high (23.1%; OR[1] 14, 95% CI[2] 2.5–78).

Conclusions: Screening asymptomatic subjects identifies a significant number of neoplastic lesions at an early stage. Incorporating data on genetic polymorphisms in the APC and CD24 genes can further identify individuals who are at increased risk for cancer. Cancer can be prevented and/or diagnosed at an early stage using the screening facilities of a multidisciplinary outpatient clinic.

Background: Sporadic abdominal desmoid tumors are rare and data on these tumors as a distinct disease entity are lacking. Previous abdominal surgery, trauma, pregnancy and estrogen intake are considered risk factors. Although desmoidsare benign, invasion and a high recurrence rate are common.

Objectives: To evaluate outcomes of surgery for this rare disease.

Methods: Since 1995, 16 patients with pathologically confirmed desmoid tumor were operated on in our center. All familial adenomatous polyposis patients were excluded. A retrospective analysis of data was performed.

Results: Of the 16 patients 12 (75%) were females. Mean age was 40.5 years (range 24-70). Thirteen patients were symptomatic and 3 were incidentally diagnosed. All patients presented with an isolated mass; 7 (50%) originated in the abdominal wall, 6 (37.5%) were retroperitoneal and 3 were (18.8%) mesenteric. All tumors except one were completely excised. Morbidity was low with no mortality. One patient was reoperated due to involved margins. None of the patients had recurrence within a median follow-up of 64 months (range 5-143).

Conclusions: The perception of sporadic abdominal desmoids as tumors with a high recurrence rate (20-70%) is probably incorrect. Adequate surgery with wide margins leads to a very low recurrence rate; cure is a legitimate goal.
 

Mesenchymal stem cells, or mesenchymal stromal cells, have emerged as a major new cell technology with a diverse spectrum of potential clinical applications. MSCs[1] were originally conceived as stem/progenitor cells to rebuild diseased or damaged tissues. Over the last 14 years, since the first report of MSC infusions in patients, the cells have been shown to suppress graft vs. host disease, stimulate linear growth in a genetic disorder of bone, and foster engraftment of haplo-identical hematopoietic stem cells. In all cases, few, if any, MSCs were identified at the site of clinical activity. This experience suggests a remarkable clinical potential, but a different general mechanism of action. Systemically infused MSCs seem to exert a therapeutic effect effect through the release of cytokines that act on local, or perhaps distant, target tissues. Rather than serving as stem cells to repair tissues, they serve as cellular factories that secrete mediators to stimulate the repair of tissues or other beneficial effects. Since both the tissue source of MSCs and the ex vivo expansion system may significantly impact the cytokine expression profile, these parameters may be critically important determinants of clinical activity. Furthermore, cell processing protocols may be developed to optimize the cell product for a specific clinical indication. For example, MSC-like cells isolated from placenta and expanded in a three-dimensional bioreactor have recently been shown to increase blood flow in critical limb ischemia. Future efforts to understand the cytokine expression profile will undoubtedly expand the range of MSC clinical applications.

Background: Dyslipidemia remains underdiagnosed and undertreated in patients with coronary artery disease. The Computer-based Clinical Decision Support System provides an opportunity to close these gaps.

Objectives: To study the impact of computerized intervention on secondary prevention of CAD[1].

Methods: The CDSS[2] was programmed to automatically detect patients with CAD and to evaluate the availability of an updated lipoprotein profile and treatment with lipid-lowering drugs. The program produced automatic computer-generated monitoring and treatment recommendations. Adjusted primary clinics were randomly assigned to intervention (n=56) or standard care arms (n=56). Reminders were mailed to the primary medical teams in the intervention arm every 4 months updating them with current lipid levels and recommendations for further treatment. Compliance and lipid levels were monitored. The study group comprised all patients with CAD who were alive at least 3 months after hospitalization.

Results: Follow-up was available for 7448 patients with CAD (median 19.8 months, range 6–36 months). Overall, 51.7% of patients were adequately screened, and 55.7% of patients were compliant with treatment recommended to lower lipid level. A significant decrease in low density lipoprotein levels was observed in both arms, but was more pronounced in the intervention arm: 121.9 ± 34.2 vs. 124.3 ± 34.6 mg/dl (P < 0.02). A significantly lower rate of cardiac rehospitalizations was documented in patients who were adequately treated with lipid-lowering drugs, 37% vs. 40.9% (P < 0.001).

Conclusions: This initial assessment of our data represent a real-world snapshot where physicians and CAD patients often do not adhere to clinical guidelines, presenting a major obstacle to implementing effective secondary prevention. Our automatic computerized reminders system substantially facilitates adherence to guidelines and supports wide-range implementation.

Background: Myeloperoxidase levels were shown to reflect endothelial dysfunction, inflammation, atherosclerosis and oxidative stress.

Objectives: To examine the role of circulating myeloperoxidase, a leukocyte-derived enzyme, as a predictor of mortality in patients with congestive heart failure.

Methods: Baseline serum MPO[1] levels were measured in 285 consecutive CHF[2] patients and 35 healthy volunteers. N-terminal pro-brain natriuretic peptide and high sensitivity C-reactive protein concentrations were also measured. The primary outcome endpoint was overall mortality.

Results: MPO levels were significantly elevated in patients with CHF compared to healthy volunteers (P = 0.01). During a mean follow-up of 40.9 ± 11.3 months there were 106 deaths. On a univariate Cox regression analysis MPO levels were of marginal value (P = 0.07) whereas NT-proBNP[3] was of considerable value (P < 0.0001) in predicting all-cause mortality. By dividing our cohort according to NT-proBNP levels into high, intermediate and low risk groups a clear difference in mortality was shown. By further dividing the patient cohort according to MPO levels above or below the median (122.5 ng/ml), mortality prediction improved in the patients with intermediate NT-proBNP values.

[1] MPO = myeloperoxidase

[2] CHF = congestive heart failure

[3] NT-proBNP = N-terminal pro-brain natriuretic peptide

Background: A polymeric diet rich in transforming growth factor-beta 2 used as a single nutrient has been shown to induce remission in 79% of children with Crohn's disease.

Objectives: To summarize the experience of several pediatric gastroenterology units in Israel using a TGFβ2[1]-enriched polymeric diet (Modulen IBD) supplementation in children and adolescents with Crohn's disease.

Methods: In a retrospective study we reviewed the charts of 28 children with Crohn's disease (10 girls, 18 boys) who received, in addition to conventional treatment, Modulen IBD™ as a supplement to their regular nutrition. These children were compared with 18 children supplemented with standard polymeric formula (Ensure Plus®) and 18 children without formula supplementation. We recorded clinical manifestations, growth, and the Pediatric Crohn's Disease Activity Index before and after initiation of the polymeric diet.

Results: The Modulen-treated children showed a significant decrease in PCDAI[2] from 34.3 to 15.7 (P < 0.0001). A significant decrease in PCDAI was recorded also in the Ensure Plus group, from 35 to 22 (P = 0.02) but not in the non-supplemented group. Significant improvements in body mass index (P = 0.01) and erythrocyte sedimentation rate (P = 0.03) were recorded at follow-up (median 3.4 months) only in the Modulen IBD group.

Conclusions: In this cohort of children with Crohn's disease, supplementation of the diet with Modulen IBD as well as supplementation with Ensure Plus was associated with a decrease in PCDAI. The children supplemented with Modulen IBD also showed improvement in BMI[3], suggesting an additional advantage of nutritional therapy in children with this disease.

Background Voiding cystourethrogram is performed 3–6 weeks after urinary tract infection. This prolongs the interval of prophylactics, reducing the likelihood of performing the procedure.

Objectives To investigate the yield and potential risks/benefits of early compared to late-performance VCUG[1] after UTI[2].

Methods We conducted a prospective study of 84 previously healthy children < 5 years old admitted from October 2001 to November 2002 with first documented UTI. We then divided the 78 patients who had VCUG into two groups and compared them to a control group:  group A – 49 children in whom VCUG was performed within 10 days, group B – 29 children in whom VCUG was performed > 10 days after UTI, and a historical control group C – 82 children in whom VCUG was performed > 4 weeks following UTI.

Results VCUG was performed in 48/48 (100%), 6/35 patients (17.1%), 34/116 patients (29.3%) and vesicoureteral reflux was demonstrated in 38.8%, 37.9%, 39% in groups A, B, C respectively. No significant difference was found between these groups in terms of incidence of VUR[3] and severity and grading of reflux within each group. One case of UTI secondary to VCUG occurred in a patient in whom the procedure was performed 4 months after the diagnosis.

Conclusions Performing VCUG early does not influence detection rate, severity of the VUR, or risk of secondary infection; it shortens the period of prophylactic use and increases performance rate of VCUG, thereby minimizing the risk of failure to detect VUR. The traditional recommendation of performing VCUG 3–6 weeks after the diagnosis of UTI should be reevaluated.