Plasma from patients undergoing major open surgery stimulates in vitro tumor growth: Lower insulin-like growth factor binding protein 3 levels may,in part,account for this change

BACKGROUND: Plasma from laparotomized mice has been shown to stimulate in vitro tumor growth when compared to results with preoperative plasma. This study assessed the effect of plasma from patients who underwent major open (OS) or laparoscopic surgery (LS) on in vitro tumor cell growth. METHODS: Eighty-four patients undergoing major abdominal surgery were studied (45 OS, 39 LS). Peripheral blood was collected preoperatively (PreOP) and on days 1 (POD1) and 3 (POD3) after operation. HT29 human colon cancer cells were plated with samples of the plasma. Proliferation was assessed by cell counts and the bromodeoxyuridine incorporation assay. Insulin-like growth factor binding protein 3 was detected in plasma by Western blot analysis. RESULTS: Increased mitogenic activity was noted in POD1 OS plasma when compared to PreOP OS plasma results (P <.005). This increase correlated with the length of incision (r = 0.58, P <.01). No differences were noted when the PreOP LS and POD1 LS results were compared or for any of the POD3 versus PreOP comparisons. CONCLUSIONS: Major OS is associated with alterations in plasma composition that promote HT29 tumor cell proliferation in vitro. As shown, this effect was due, at least in part, to surgery-related depletion of insulin-like growth factor binding protein 3 in peripheral blood.     

B cell response to tumor antigens is associated with depletion of B progenitors in murine colocarcinoma

BACKGROUND: B cells that produce antibodies to autologous tumor antigens have been found in patients with colon cancer; the significance of this phenomenon remains unknown. Normally, the elimination of autoreactive B cells occurs in the bone marrow during their maturation. We studied the production of antibodies to syngeneic tumor antigens and the maturation of bone marrow B cells in experimental colocarcinoma model. METHODS: BALB/c mice and syngeneic CT26 colon cancer cell line were used. Reactivity of serum antibodies was tested in Western blot analysis and flow cytometry against CT26 antigens. The number of bone marrow B lineage cells was evaluated with specific antibodies and flow cytometry analysis. RESULTS: A significant decrease in the number of B cell precursors occurred in tumor-bearing mice; it normalized 3 weeks after the removal of CT26 tumors. The number of mature B cells was normal. Serum antibodies from tumor-bearing mice recognized intracellular and not surface antigens of CT26 cells. CONCLUSION: Experimental colon cancer induces B cell response to intracellular, but not surface, tumor cell antigens and restricts the B cell repertoire by depleting their precursors.     

Safety and reliability of tattooing colorectal neoplasms prior to laparoscopic resection

Accurate tumor localization is critical to performing minimally invasive colorectal resection. This study reviews the safety and reliability of tattooing colorectal neoplasms prior to laparoscopic resection. Weretrospectively reviewed 50 consecutive patients with colorectal neoplasms who underwent endoscopic tattooing prior to laparoscopic resection. Data were obtained from medical charts, endoscopy records, and pathology reports. No complications related to endoscopy or tattooing were incurred. Five neoplasms (10%) were in the ascending colon, five (10%) were in the transverse colon, eight (16%) were in the descending colon, 23 (46%) were in the sigmoid colon, and nine (18%) were in the rectum. Tattoos were visualized intraoperatively and accurately localized the neoplasm in 44 patients (88%). Six patients (12%) did not have tattoos visualized laparoscopically and required intraoperative localization. On average, the pathology specimens in this series had a 15 cmproximal margin, a 12 cmdistal margin, and 15 lymph nodes. In the context of laparoscopic colorectal resection, preoperative endoscopic tattooing is a safe and reliable method of tumor localization in most cases. Localizing colon and proximal rectal lesions with tattoos may be preferable to other localization techniques including intraoperative endoscopy.     

Morphologic reappraisal of serrated colorectal polyps

The "hyperplastic polyp" is considered a benign lesion with no malignant potential, whereas "serrated adenoma" is a precursor of adenocarcinoma. The morphologic complexity of the serrated adenoma varies from being clearly adenomatous to being difficult to distinguish from hyperplastic polyp, which creates a need for more detailed morphologic analysis of all serrated polyps. We evaluated 24 morphologic variables in 289 serrated polyps from the colon and rectum. Cluster analysis and discriminant analysis were performed. A subset of polyps was immunostained for hMLH1 and hMSH2. Major differences were found between right-sided and left-sided polyps. A distinct group of serrated polyps with abnormal proliferation was identified throughout the colon and rectum. These polyps demonstrated decreased expression of hMHL1 and hMSH2 compared with polyps with normal proliferation. Left-sided serrated polyps with normal proliferation further clustered into three groups: vesicular cell-type, goblet cell-type, and mucin-poor-type. We recommend evaluation of the localization, size, and morphologic features when serrated polyps are included in colorectal carcinogenesis research. Polyps with abnormal proliferation are similar to the polyps in "hyperplastic polyposis" and, because of their decreased expression of hMLH1 and hMSH2, may be the subset of polyps associated with the development of colorectal carcinoma via the microsatellite instability pathway.     

Expression of bcl-6 and CD10 protein is associated with longer overall survival and time to treatment failure in follicular lymphoma

Follicular lymphomas (FLs) are a heterogeneous group of tumors, but prognostic factors are evaluated insufficiently in this common hematologic neoplasm. While bcl-6 and CD10 are expressed characteristically in FLs, their significance for biologic behavior of FL has not been studied previously. Samples from 73 patients with FL and clinical follow-up from 7 to 231 months were evaluated by immunohistochemical analysis. Patients with high levels of bcl-6 expression had favorable overall survival (OS) (P = .003), disease-specific survival (DSS) (P = .033), and time to treatment failure (P = .003) compared with patients with low levels of bcl-6 expression. Multivariate analysis showed that the results for OS, DSS, and time to treatment failure were independent of the international prognostic index. Patients with CD10+ FLs also had longer OS (P = .001), DSS (P = .007), and time to treatment failure (P = .004), and grade 1 FL was associated with better OS (P = .01) and a statistical trend for longer DSS (P = .05) and time to treatment failure (P = .05), but these results were not independent of bcl-6 expression or the international prognostic index in multivariate analysis.     

Prognostic factors in patients who have survived myocardial infarction

Patients who have survived myocardial infarction (MI), compared to the general population, have an increased risk of reinfarction, myocardial revascularization, and death. In this study we investigated the prognostic significance of the predictors of the risk for adverse coronary events in 118 patients, both male and female, with a confirmed diagnosis of MI in the last 3 years. The predictors of reinfarction, revascularization and death in patients who survived MI were: poor adherence to hypolipemics (hazard ratio [HR] 3.06, p=0.006), physical inactivity (HR 2.22, p=0.056), the number of variable risk factors (HR 1.29, p=0.025), and age (HR 1.06, p=0.007). After the inclusion of the invariable risk factors in the model of multivariant analysis, the following factors were singled out as significant predictors of the risk: gender (HR 3.86, p=0.0015), physical inactivity (HR 2.38, p=0.007), change in the level of triglycerides (HR 1.49, p=0.040), change in the number of variable risk factors (HR 1.41, p=0.0007), and age (HR 1.05, p=0.009). A 3-year follow-up of the patients who survived the first MI and who were enrolled in this study of secondary prevention demonstrated that physical inactivity, the number of variable risk factors and age significantly contributed to an increased risk of reinfarction, revascularization, and death.     

Developmental characteristics of children aged 1-6 years with food refusal.

OBJECTIVE: The aim of this study was to compare the sociodemographic and developmental characteristics of children with food refusal and children with no history of feeding problems. DESIGN: Cross-sectional case-control study. SAMPLE: 30 children aged 1-6 years who were seen in the outpatient clinics for food refusal formed the case group, and 30 healthy children matched for age, sex, and socioeconomic status formed the control group. METHODS: Anthropometric indices and early developmental characteristics of all the children in the study were evaluated and also their developmental levels were determined using the Ankara Developmental Screening Inventory. RESULTS: The mean age of children with food refusal was 42.4+/-17.6 months, and the male/female ratio was 12/18. Children with food refusal had shorter mean breastfeeding durations and lower mean birth weights, body mass index, percentage height for age, and percentage weight for height values than those of the controls. There were no significant differences between the 2 groups in developmental delays. CONCLUSIONS: These results suggest that food refusal may be related to lower birth weight and shorter breastfeeding duration. Further research with larger samples is needed to clarify these relationships and the effects of feeding problems on the growth and development of children.     

The role of lecithin cholesterol acyltransferase and organic substances from coal in the etiology of Balkan endemic nephropathy: a new hypothesis.

Balkan endemic nephropathy (BEN) occurs in Serbia, Bulgaria, Romania, Bosnia and Herzegovina, and Croatia. BEN has been characterized as a chronic, slowly progressive renal disease of unknown etiology. In this study, we examined the influence of soluble organic compounds in drinking water leached from Pliocene lignite from BEN-endemic areas on plasma lecithin-cholesterol acyltransferase (LCAT) activity. We found that changes for all samples were the most prominent for the dilution category containing 90% plasma and 10% of diluting media. Water samples from BEN villages from Serbia and Romania showed higher LCAT inhibiting activity (p=0.02) and (p=0.003), respectively, compared to deionised water and non-endemic water. A secondary LCAT deficiency could result from this inhibitory effect of the organic compounds found in endemic water supplies and provide an ethiopathogenic basis for the development of BEN in the susceptible population.     

Prothrombogenic factors and reduced antioxidative defense in children and adolescents with pre-metabolic and metabolic syndrome.

BACKGROUND: The aim of this study was to examine prothrombogenic factors and antioxidative defense in obese children and adolescents with pre-metabolic and metabolic syndrome, and to analyze insulin secretion and resistance, early glycoregulation disorders and lipid status. METHODS: Insulin sensitivity was determined using the homeostasis model assessment for insulin resistance (HOMA-IR), while insulin secretion was determined using the homeostasis model assessment beta (HOMA-beta). Prothrombogenic factors analyzed were plasma plasminogen activator inhibitor-1 (PAI-1) and fibrinogen. Superoxide dismutase and glutathione peroxidase were measured as markers of antioxidative defense. RESULTS: Patients with metabolic syndrome were characterized with increased body mass index (BMI), waist circumference, and HOMA-IR and HOMA-beta levels, and all had increased blood pressure and triglyceride levels, low high-density lipoprotein cholesterol levels, increased PAI-1 levels and reduced antioxidative defense levels. Patients with pre-metabolic syndrome had higher levels of basal and mean insulinemia during an oral glucose tolerance test, higher levels of HOMA-beta and lower levels of antioxidative defense compared to patients with metabolic syndrome. CONCLUSIONS: Negative correlations between antioxidative defense parameters and BMI, abdominal obesity, insulin secretion, systolic blood pressure and atherogenic lipid factors, as well as correlations between PAI-1 and insulin resistance and basal glycemia in the metabolic syndrome group contribute to accelerated atherosclerosis. Positive correlations between PAI-1 and waist circumference and BMI, and negative correlations between BMI and antioxidative defense in the pre-metabolic syndrome patients show that this early stage preceding the metabolic syndrome is also characterized by atherosclerotic complication risks and evident hyperinsulinism and insulin resistance.