PLA2 (group IIA phospholipase A2) as a prognostic determinant in stage II colorectal carcinoma.

BACKGROUND: Approximately 30% of all colorectal cancer (CRC) patients are diagnosed with stage II disease. Adjuvant therapy is not widely recommended. However, it is well established that a subgroup of patients with stage II are at high risk for recurrence within their lifetime and should be considered for adjuvant chemotherapy. The present work was designed to assess the value of group IIA phospholipase A2 (PLA2) as a predictor of disease outcome in stage II CRC patients with long-term follow-up. PATIENTS AND METHODS: The present study comprises a series of 116 patients who underwent bowel resection for stage II CRC during 1981-1990 at Turku University Hospital. Archival paraffin-embedded CRC tissue samples were used to prepare tissue microarray blocks for immunohistochemical staining with PLA2. RESULTS: Fifty-five percent of all tumors were positive for PLA2. There was no significant correlation between PLA2 expression and age, sex, depth of invasion and lymph node status. In Kaplan-Meier survival analysis, there was a significant (P = 0.010) difference in disease-free survival (DFS) between patients with negative tumors (longer DFS) and those with positive tumors. The same was true with disease-specific survival (DSS), patients with PLA2-negative tumors living significantly longer (P = 0.025). In multivariate (Cox) survival analysis, however, PLA2 was not an independent predictor of DFS or DSS. In subgroup analysis, the right-sided tumors with negative PLA2 staining had remarkably better prognosis (P = 0.010) than PLA2-positive left-sided tumors. CONCLUSIONS: Quantification of PLA2 expression seems to provide valuable prognostic information in stage II CRC, particularly in selecting the patients at high risk for recurrent disease who might benefit from adjuvant therapy.

Induced expression of syndecan in healing wounds.

We have studied the expression of an integral cell surface proteoglycan, syndecan, during the healing of cutaneous wounds, using immunohistochemical and in situ hybridization methods. In normal mouse skin, both syndecan antigen and mRNA were found to be expressed exclusively by epidermal and hair follicle cells. After incision and subsequent suturing, remarkably increased amounts of syndecan on the cell surfaces of migrating and proliferating epidermal cells and on hair follicle cells adjacent to wound margins were noted. This increased syndecan expression was shown to be a consequence of greater amounts of syndecan mRNA. Induction was observed already 1 d after wounding, was most significant at the time of intense cell proliferation, and was still observable 14 d after incision. The migrating cells of the leading edge of the epithelium also showed enhanced syndecan expression, although clearly less than that seen in the proliferating epithelium. The merging epithelial cells at the site of incision showed little or no syndecan expression; increased syndecan expression, however, was detected during later epithelial stratification. When wounds were left unsutured, in situ hybridization experiments also revealed scattered syndecan-positive signals in the granulation tissue near the migrating epidermal sheet. By immunohistochemical analysis, positive staining in granulation tissue was observed around vascular endothelial cells in a subpopulation of growing capillaries. Induction of syndecan in granulation tissue both at the protein and mRNA levels was temporally and spatially highly restricted. Granulation tissue, which formed in viscose cellulose sponge cylinders placed under the skin of rats, was also found to produce 3.4 and 2.6 kb mRNA species of syndecan similar to that observed in the normal murine mammary epithelial cell line, NMuMG. These results suggest that syndecan may have a unique and important role as a cell adhesion and a growth factor-binding molecule not only during embryogenesis but also during tissue regeneration in mature tissues.

DNA image cytometry predicts disease outcome in stage II colorectal carcinoma.

BACKGROUND: Approximately 30% of all colorectal cancer (CRC) patients are diagnosed with stage II disease. Adjuvant therapy is not widely recommended. However, it is well established that a subgroup of patients with stage II are at high risk for recurrence within their lifetime and should be considered for adjuvant chemotherapy. The present work was designed to study the prognostic value of nuclear DNA content in stage II CRC of patients with long-term followup. PATIENTS AND METHODS: Isolated nuclei from 50 microm-thick paraffin sections of tissue samples from 253 patients with stage II CRC, who had undergone bowel resection at Turku University Central Hospital were cytocentrifuged on slides, stained with Feulgen staining, and DNA was measured using a computer-assisted image analysis cytometry system. Different approaches were applied in analysis of DNA histograms. RESULTS: DNA content did not show any relation with age (p < 0.96), sex (p < 0.35), tumor invasion (p < 0.77), or grade (p < 0.31). Aneuploid DNA content was significantly more frequent in the cancer of the left colon and rectum than the right colon (p = 0.02). S-phase fraction analysis revealed that a higher proportion (62%) of the older patients (>65 years) had high proliferation rates than did the younger patients (p < 0.05). Patients with narrow range histograms had a better disease-free survival (DFS) (narrow range: 70%, wide range: 60% at 10 years). Tumors with >9c nuclei were associated with significantly better DFS and disease-specific survival (DSS) as compared with the patients who did not have >9c nuclei in their tumor samples (p < 0.003 and p < 0.0001, respectively). Multivariate survival (Cox) model showed that only classification of the basic pattern of the histogram [odds ratio OR) = 29.14; 95% confidence interval (CI) 2.350-361.57] (p = 0.009) and recurrence (OR = 165.35; 95% CI 48.42-564.7) (p = 0.0001) proved to be independent predictors of clinical outcome. CONCLUSION: Our results seem to suggest it truly is possible, by using DNA cytometry, to find groups with different prognosis among stage II cases. Those with a high recurrence rate should be considered for adjuvant chemotherapy.

Hypoxia Marker GLUT-1 (Glucose Transporter 1) is an Independent Prognostic Factor for Survival in Bladder Cancer Patients Treated with Radical Cystectomy.

BACKGROUND: Tumour hypoxia, which is frequent in many cancer types, is associated with treatment resistance and poor prognosis. The role of hypoxia in surgically treated bladder cancer (BC) is not well described. We studied the role of hypoxia in two independent series of urothelial bladder cancers treated with radical cystectomy. METHODS: 279 patients from the University Hospital Network (UHN), Toronto, Canada, and Turku University, Finland were studied. Hypoxia biomarkers (HIF1-α, CAIX, GLUT-1) and proliferation marker Ki-67 were analyzed with immunohistochemistry using defined tissue microarrays. Kaplan-Meier methods and Cox proportional hazards regression models were used to investigate prognostic role of the factors. RESULTS: In univariate analyses, strong GLUT-1 positivity and a high Ki-67 index were associated with poor survival. In multivariate model containing clinical prognostic variables, GLUT-1 was an independent prognostic factor associated with worse disease-specific survival (HR 2.9, 95% CI 0.7-12.6, Wald p = 0.15 in the Toronto cohort and HR 3.2, 95% CI 1.3-7.5, Wald p = 0.0085 in the Turku cohort). CONCLUSION: GLUT-1 is frequently upregulated and is an independent prognostic factor in surgically treated bladder cancer. Further studies are needed to evaluate the potential role of hypoxia-based and targeted therapies in hypoxic bladder tumours.

Upregulation of tumor suppressor protein neurofibromin in normal human wound healing and in vitro evidence for platelet derived growth factor (PDGF) and transforming growth factor-beta1 (TGF-beta1) elicited increase in neurofibromin mRNA steady-state levels in dermal fibroblasts.

We first studied expression of neurofibromin by immunohistochemistry in scars obtained from operations involving areas of healing wounds. The results demonstrated increased immunoreactivity for neurofibromin in the fibroblastic cell population of the lesions when compared with fibroblasts of apparently healthy perilesional skin, or those of intact control skin. Furthermore, dermal fibroblasts of 19 and 34 wk-old fetuses displayed a clearly detectable immunosignal for neurofibromin. In vitro studies were designed to investigate the potential effects of selected growth factors--known to be operative in wound healing--on neurofibromin mRNA steady-state levels in cultured fibroblasts. Northern transfer analyses revealed that different isoforms of platelet derived growth factor (PDGF) exerted selective effects on the neurofibromin mRNA levels: PDGF isoform AB elevated neurofibromin mRNA levels in a concentration-dependent manner when concentrations of 0.1, 1, 10, and 30 ng per ml were used. The maximal upregulatory effect of PDGF BB was reached at a concentration of 1 ng per ml. In contrast, PDGF AA did not alter the steady-state levels of neurofibromin mRNA. As estimated by RNase protection assay, transforming growth factor-beta1 (TGF-beta1) upregulated neurofibromin gene expression when concentrations of 0.5 and 5 ng per ml were used. Reverse transcription followed by polymerase chain reaction did not detect apparent alterations in the ratio of type I/type II neurofibromin isoforms in PDGF- or TGF-beta1-treated cultures. Taken together, our results suggest that expression of tumor suppressor protein neurofibromin is upregulated in response to skin injury, and that this upregulation can be mediated through PDGF and TGF-beta.

New function for NF1 tumor suppressor.

The expression and subcellular localization of neurofibromatosis type 1 tumor suppressor was studied in keratinocytes induced to differentiate by increased Ca2+ concentration of the culture medium. Differentiating keratinocytes became intensely immunoreactive for neurofibromatosis type 1 protein, which was apparently associated with cellular fibrils. Double immunolabeling with antibodies to cytokeratin 14 and neurofibromatosis type 1 protein suggested an association of intermediate type cytoskeleton and neurofibromatosis type 1 protein. The presence of neurofibromatosis type 1 protein in cell preparations treated with cytoskeletal buffer indicated a high affinity interaction between intermediate filaments and neurofibromatosis type 1 protein. Further studies utilizing double immunolabelings revealed that the intense neurofibromatosis type 1 tumor suppressor signal on intermediate filaments was temporally limited to the period in keratinocyte differentiation in which the formation of desmosomes takes place. Keratinocytes were also cultured from nine patients with type 1 neurofibromatosis and were studied with respect to cell morphology, and association of neurofibromatosis type 1 protein with intermediate cytoskeleton. The results showed that keratinocytes cultured from patients with neurofibromatosis type 1 displayed a highly variable cell size and morphology compared to controls. The latter findings represent predicted alterations in a situation where cytoskeletal organization is disturbed. Furthermore, differentiating neurofibromatosis type 1 keratinocytes were characterized by a reduced number of cytokeratin bundles that were decorated neurofibromatosis type 1 protein. The results of this study suggest that neurofibromatosis type 1 tumor suppressor exerts its effects in part by controlling organization of cytoskeleton during the formation of cellular contacts.

Inhibin gene expression in a large cell calcifying Sertoli cell tumour and serum inhibin and activin levels.

Inhibin is a potential tumour suppressor gene product in the gonads. While inhibin gene products may have a role in tumourigenesis, serum inhibin levels can be used as a marker for ovarian tumours derived from granulosa cells. Tumours derived from Sertoli cells, testicular counterparts of granulosa cells, are rare. To assess whether inhibin could be used as a human Sertoli cell tumour marker, serum inhibin and activin levels and inhibin subunit mRNA expression in the testis were studied. Northern blot and in situ hybridization revealed abundant expression of inhibin alpha, beta A, and beta B subunit mRNAs in large cell calcifying Sertoli cell tumours found in a 12-year old boy with Carney complex. The tumours were multifocal and bilateral. Serum inhibin levels were clearly elevated at the time of the diagnosis, decreased by 50% after one of the testes was removed, and were low or undetectable after the second orchidectomy six weeks later. Activin was undetectable before the orchidectomies, while a low concentration of activin-A was measured after them. Follicle stimulating hormone (FSH) concentration increased from normal pubertal value to castration level as expected. Normal seminiferous tubules also showed inhibin subunit alpha and beta B mRNA expression, whereas inhibin beta A mRNA was expressed in normal Leydig cells. These data suggest that serum inhibin reflects Sertoli cell activity and can be used as a human tumour marker.

Are serum inflammatory markers age dependent in acute appendicitis?

BACKGROUND: Preoperative measurement of body inflammatory agents reduces unnecessary appendectomies by up to 30 percent. A decline in the formation of blood leukocytes and C-reactive protein with aging may hinder the correct diagnosis of appendicitis. STUDY DESIGN: White cell count and C-reactive protein were determined before appendectomy in 600 patients aged 0 to 5 years, 6 to 19 years, 20 to 39 years, 40 to 59 years, 60 to 79 years, and older than 80 years. Their records were analyzed. The sensitivity, specificity, diagnostic accuracy, and receiver-operating characteristic curves for C-reactive protein and white cell count to predict appendicitis were calculated separately for each age group. RESULTS: The rates of negative explorations and perforations were highest at both extremes of age. In uncomplicated appendicitis, the diagnostic potential of white cell count was better than C-reactive protein in all age groups except infants. The C-reactive protein was elevated similarly throughout human life, but only in those with perforated appendicitis. The receiver-operating characteristic curves confirmed that the performance of white cell count was better than C-reactive protein in the correct diagnosis in every age group except infants and octogenarians. CONCLUSIONS: The leukocyte response declines in 0- to 5-year-old children with appendicitis, but the C-reactive protein response is well preserved in all other age groups.

Expression of cyclooxygenase-1 and -2 in urinary bladder carcinomas in vivo and in vitro and prostaglandin E2 synthesis in cultured bladder cancer cells.

Cyclooxygenases (Coxs) are the rate-limiting enzymes catalysing the formation of prostaglandins, which are involved in various of physiological processes. Increased Cox-2 expression has been observed in several malignancies, but the exact role of Cox-2 in carcinogenesis remains unsolved. We studied the expression of both Cox-1 and Cox-2 by immunohistochemistry in 29 transitional cell carcinomas of the urinary bladder. Diffuse cytoplasmic immunosignal for Cox-2 was detected in all cancer specimens. The expression was moderate in 55% and strong in 31% of the carcinomas. The normal urothelium in the samples stained also for Cox-2, but the intensity of the immunosignal was weak in most specimens. Cox-1 was expressed in the stroma of bladder wall, whereas in the tumour cells, Cox-1 immunosignal was either absent or weak. No correlation was detected between Cox-1 or Cox-2 expression and tumour differentiation or stage of invasion. We also evaluated the mRNA expression of Cox-1 and Cox-2 and synthesis of prostaglandin E2 (PGE2) in three bladder carcinoma cell lines (RT4, 5637, and T24). All cell lines expressed high levels of Cox-2 mRNA, whereas Cox-1 mRNA expression was detected only in T24 cells. There was great variation in the basal levels of PGE2 synthesis in these cell lines. Indomethacin inhibited the synthesis of PGE2 in all three cell lines, although the level of Cox-2 mRNA tended to increase by indomethacin. These results indicate that Cox-2 is widely expressed in human bladder carcinomas and that the role of Cox-2 inhibition in bladder cancer should be further studied.

Differential effects of hexoses and sucrose, and platelet-derived growth factor isoforms on cyclooxygenase-1 and -2 mRNA expression in keloid, hypertrophic scar and granulation tissue fibroblasts.

Cyclooxygenase (COX) is the key enzyme in the formation of prostaglandins in inflammation. In the present study the effects of biomedically relevant hexose sugars (glucose, fructose, galactose, mannose) and sucrose disaccharide on the expression of COX-1 and COX-2 genes were evaluated in granulation tissue fibroblasts, hypertrophic scar fibroblasts and keloid fibroblasts. The effects of three isoforms (AA, AB and BB) of PDGF on COX gene expression in granulation tissue fibroblasts were also examined. All cell lines expressed COX-1 mRNA, whilst fibroblasts derived from abnormal scars did not express COX-2 mRNA. COX-1 mRNA expression was decreased by sugars in granulation tissue fibroblasts and increased in hypertrophic scar fibroblasts. No major changes were seen in keloid fibroblasts. On the other hand, COX-2 mRNA expression in granulation tissue fibroblasts was decreased dramatically in the presence of fructose, mannose and sucrose and moderately in the presence of galactose. All isoforms of PDGF increased COX-1 and COX-2 mRNA expression in granulation tissue fibroblasts, the most marked increases being elicited by PDGF-BB. All fibroblast cell lines studied expressed the COX-1 gene while the COX-2 gene was not expressed by abnormal scar-derived fibroblasts. Further, granulation tissue fibroblasts seemed to behave differently under the influence of sugars compared to hypertrophic scar fibroblasts whilst keloid fibroblasts seemed to be relatively unaffected by sugars. In addition, the PDGF-BB isoform is a potent inducer of COX-2 gene expression in wound fibroblasts. These findings may be relevant to the development of abnormal scars and indicate the need for further studies.

The effects of interleukin-1 and prostaglandin E2 on accumulation of collagen and steady-state levels of pro alpha 1(I) collagen messenger RNA in experimental granulation tissue in rats.

The effects of human interleukin 1 beta (IL-1 beta) and prostaglandin E2 (PGE2) on experimental granulation tissue in rats and on granulation tissue cells in culture were studied. IL-1 beta and PGE2 were injected into subcutaneously implanted sponges during the first 3 days after implantation. The rate of collagen synthesis in fibroblasts was measured as synthesis of protein-bound 3H-hydroxyproline. The steady-state levels of pro alpha 1(I) and pro alpha 1(III) collagen chain mRNAs were estimated by Northern transfer analyses. By 7 days postoperatively IL-1 beta had decreased the hydroxyproline content of granulation tissue. PGE2 decreased non-significantly the amounts of hydroxyproline, but the steady-state levels of pro alpha 1(I) and pro alpha 1(III) collagen chain mRNAs were slightly elevated. In IL-1 beta-treated fibroblast cultures collagen production decreased by 15% and following PGE2 treatment by 34% compared with the controls. The latter effect could be abolished by indomethacin. Indomethacin alone stimulated collagen production by 40%. In vivo IL-1 decreases the formation of normal granulation tissue. This effect may be partly due to stimulation of secretion of PGE2.

A fibroblast cell line cultured from a hypertrophic scar displays selective downregulation of collagen gene expression: barely detectable messenger RNA levels of the pro alpha 1(III) chain of type III collagen.

The present study was designed to investigate the expression of type I, III and VI collagens by a fibroblast cell line initiated from a hypertrophic scar. The same tissue has previously been demonstrated to display markedly elevated expression of type I and III collagen mRNAs in vivo. Unexpectedly, slot-blot and Northern hybridizations revealed a barely detectable steady-state level of pro alpha 1(III) collagen chain mRNA in cultured hypertrophic scar fibroblasts. The levels of pro alpha 1(I) and alpha 2(VI) collagen chain mRNAs were essentially the same in fibroblasts cultured from hypertrophic scar and in fibroblasts cultured from normal skin. However, Northern blot analyses indicated that the ratio of 5.8 kb to 4.8 kb species of pro alpha 1(I) collagen mRNA was slightly reduced in fibroblasts originating from the hypertrophic scar compared to that in normal fibroblasts. When normal fibroblasts were incubated in conditioned medium from hypertrophic scar cultures, the expression of pro alpha 1(III) collagen chain mRNA decreased to a markedly lower level. Our studies suggest that collagen synthesis by fibroblasts in hypertrophic scars is stimulated by humoral factors which are active only in vivo. Furthermore, the results suggest that fibroblasts cultured from hypertrophic scar display a selective downregulation of different collagen genes and that this downregulation is exerted through an autocrine mechanism.

Magnetization transfer imaging of lumbar disc degeneration. Correlation of relaxation parameters with biochemistry.

OBJECTIVES: The authors attempted to find out if magnetization transfer (MT) imaging with magnetic resonance imaging (MRI) provides new information of disc degeneration. SUMMARY OF BACKGROUND DATA: Magnetization transfer technique improves soft-tissue contrast and characterization. It measures the cross-relaxation and chemical exchange processes between free and macromolecule-bound water protons in tissues. METHODS: The lumbar MRI and MT of four living subjects and six cadaveric spines were performed at 0.1 T. Disc water, protein, proteoglycan, and collagen contents of cadaveric samples were correlated to MT parameters. RESULTS: The rate of magnetization transfer between free-water protons and the macromolecule-bound protons was elevated in degenerated discs. A positive correlation was found between disc collagen and total protein concentration and the rate of transfer. The contrast of normal and degenerated discs on MT images was not altered much. CONCLUSIONS: More studies are needed to fully establish the importance of MT processes in the disc.

Disc degeneration in magnetic resonance imaging. A comparative biochemical, histologic, and radiologic study in cadaver spines.

Magnetic resonance imaging (MRI) findings of 89 autopsied intervertebral discs from 22 cadaveric lumbar spines were correlated with biochemical composition, conventional radiography, and histologic structure to study the nature of disc intensity changes seen in MRI. Discs with a low signal intensity on T2-weighted MRI were characterized by shortening of relaxation times, dehydration, and decreases in total proteoglycan content and chondroitin-keratan sulfate ratios in the nucleus pulposus. This corresponded well with previously published studies. In histologic structure, no obvious differences between MRI findings were found. In conclusion, a low signal intensity in a lumbar disc on T2-weighted MRI probably reflects a true biochemical disc degeneration, but its relation to structural degenerative changes is uncertain. Therefore, MRI seems to be a sensitive and a specific imaging modality for detecting pathologic biochemical disc changes in the spine of a young adult.

CD 99 and CD 106 (VCAM-1) in human testis.

AIM: The expression of the cytokines IL-2, IL-6, IL-10, IFN-g and TNF-a and the adhesion proteins CD99 and CD106 was studied in the human testis at the protein level. METHODS: The expression of the cytokines and the adhesion proteins was assessed using immunohistochemistry and immunoblotting. RESULTS: None of the cytokines studied was present in the human testis, but CD99 and CD106 (VCAM-1) strongly were expressed in all the testes investigated. CD99 was present in the interstitial tissue of the human testis as well as in the Sertoli cells. The identity of the CD99+ interstitial cells is unclear. CD106 (VCAM-1) was present in Leydig cells as well as the basal parts of the Sertoli cells in the seminiferous tubules. In immunoblotting, CD99 was demonstrated at molecular ratios of 46-57 (kD). This is a novel isoform of the molecule. CONCLUSION: The human testis produces both CD99 and CD106 and as CD106 mediates cell binding to lymphocytes, it is possible that the human Leydig cells adhere to lymphocytes like the rodent Leydig cells.

The epidemiology and treatment patterns of postoperative adhesion induced intestinal obstruction in Varsinais-Suomi Hospital District.

BACKGROUND AND AIMS: The epidemiology and treatment patterns of postoperative adhesion induced intestinal obstruction have been poorly investigated in Finland. This study evaluated the epidemiology and treatment patterns of postoperative adhesion induced intestinal obstruction in a well defined geographical area (Hospital District). MATERIAL AND METHODS: All inpatient episodes between 1.1.1999 and 31.12.1999 due to postoperative adhesion induced intestinal obstruction in Varsinais-Suomi Hospital District were evaluated retrospectively using individual patient records. RESULTS: 123 hospitalizations due to postoperative adhesion-related intestinal obstruction were observed during the study period. The total number of preceding operations was 176 considering altogether 101 patients. The most prevalent single initial operations causing adhesion induced intestinal obstruction were colorectal, upper abdominal, and female reproductive system procedures. Of all treatment episodes 32% were operative and mortality was 2%. The median days of hospital stay (range) of all inpatient episodes, operative episodes, and conservative episodes were 6 (1-58), 11 (2-34) and 4 (1-58), respectively. Patient dependent factors associated with increased likelihood to operative treatment of obstruction were: female gender (40% in females vs 23% in males, P = 0.042) and previous gynaecological surgery (70% of the patients, P = 0.032). Intraoperative findings were obstruction in 70%, strangulation in 20%, necrosis in 8%, and perforation in 2% of operations. Bowel resection was needed in 38% of operations. Preceding gynaecological surgery increased the likelihood of bowel strangulation as an intraoperative finding. CONCLUSION: The epidemiology, treatment patterns and results of postoperative adhesion induced intestinal obstruction are of the average international level in the Varsinais-Suomi Hospital District. The treatment patterns among the different hospitals in the Hospital District are similar. Female gender is associated with increased risk for operative treatment of adhesive obstruction. Previous gynaecological surgery increases the likelihood of operative treatment and complicated obstruction.

The cleansing result of oral sodium phosphate is inversely correlated with time between the last administration and colonoscopy.

BACKGROUND: There is some evidence that the timing of sodium phosphate (NaP) ingestion affects the cleansing result. The objective of this study was to evaluate the correlation of cleansing result with the timing of ingestion of NaP. METHODS: 214 consecutive outpatients scheduled to undergo colonoscopy were enrolled in the study. All patients filled out a detailed questionnaire concerning the execution of bowel cleansing. Concomitant with colonoscopy, patient characteristics were recorded and after the procedure the cleansing result was scored. The correlation between cleansing score and time from the last dose of NaP to colonoscopy was evaluated. For further analysis, patients were divided into three groups regarding the time lag from NaP taking to colonoscopy (group 1, 6 h or less; group 2, 6-12 h; group 3, 12 h or more). RESULTS: 204 patients had complete colonoscopy and enough data to be analyzed for the study. The Pearson correlation coefficient for the time between the last dose of NaP and colonoscopy was -0.450 (p=0.0001) showing an inverse correlation. The mean cleansing score (+/-SEM) of group 1 was 4.00+/-0.12, for group 2 it was 3.56+/-0.12, and for group 3 it was 2.64+/-0.14. There were statistically significant differences between all groups. CONCLUSION: The cleansing result of NaP is inversely correlated with the time between last dose of NaP and colonoscopy. Colonoscopy should be preferably performed within 12 hours of taking the second dose of NaP.

Prognostic factors in prostate cancer.

Prognostic factors in organ confined prostate cancer will reflect survival after surgical radical prostatectomy. Gleason score, tumour volume, surgical margins and Ki-67 index have the most significant prognosticators. Also the origins from the transitional zone, p53 status in cancer tissue, stage, and aneuploidy have shown prognostic significance. Progression-associated features include Gleason score, stage, and capsular invasion, but PSA is also highly significant. Progression can also be predicted with biological markers (E-cadherin, microvessel density, and aneuploidy) with high level of significance. Other prognostic features of clinical or PSA-associated progression include age, IGF-1, p27, and Ki-67. In patients who were treated with radiotherapy the survival was potentially predictable with age, race and p53, but available research on other markers is limited. The most significant published survival-associated prognosticators of prostate cancer with extension outside prostate are microvessel density and total blood PSA. However, survival can potentially be predicted by other markers like androgen receptor, and Ki-67-positive cell fraction. In advanced prostate cancer nuclear morphometry and Gleason score are the most highly significant progression-associated prognosticators. In conclusion, Gleason score, capsular invasion, blood PSA, stage, and aneuploidy are the best markers of progression in organ confined disease. Other biological markers are less important. In advanced disease Gleason score and nuclear morphometry can be used as predictors of progression. Compound prognostic factors based on combinations of single prognosticators, or on gene expression profiles (tested by DNA arrays) are promising, but clinically relevant data is still lacking.