Prostaglandin E(2) correlates with histamine production in human colorectal cancer.
Explore the source record for details and available documents.
Aged↗
Biomedical subjects
F Cianchi
Publications and source records attributed to F Cianchi.
Histamine and histidine decarboxylase up-regulation in colorectal cancer: correlation with tumor stage.
Explore the source record for details and available documents.
Colorectal Neoplasms↗
Multimodal rehabilitation for faecal incontinence: experience of an Italian centre devoted to faecal disorder rehabilitation.
BACKGROUND: Sphincter exercises and biofeedback therapy have been used to treat faecal incontinence but results have been unpredictable and standards of treatment have not yet been established. The aim of this study was to retrospectively evaluate the effects of a new multimodal rehabilitation model on faecal incontinence. METHODS: All of the rehabilitative procedures are guided by manometric data. Primary study outcome criteria were the determination of changes or deterioration in incontinence, failure to achieve full continence and/or presence of faecal urgency. The clinical outcome was designed according to the Jorge-Wexner incontinence score. RESULTS: Between 1997 and 2001, one hundred forty-nine incontinent patients (85 F and 64 M; age range, 41-73 years; mean age, 60.6 years) underwent multimodal rehabilitation at our outpatient unit. The overall mean incontinence score had significantly improved after treatment ( p<0.001), and 58 patients (38.9%) were symptom free. No patient reported any deterioration in incontinence. Faecal urgency persisted in 23 patients (15.4%). CONCLUSION: In conclusion, multimodal rehabilitation, using manometric study, can modify the incontinence score.
Adult↗
Microsatellite instability in a population of sporadic colorectal cancers: correlation between genetic and pathological profiles.
BACKGROUND: Tumours with high-frequency microsatellite instability exhibit unique genotype and phenotype features, whereas the difference between low-frequency microsatellite instability and apparently stable tumours is far from being clear. AIMS: To identify distinctive genetic and pathological characteristics of low-frequency microsatellite instability tumours. METHODS: Microsatellite instability status of 57 sporadic colorectal cancers and its correlation with genetic, pathological and clinical features was analysed. RESULTS: High frequency microsatellite instability and low-frequency microsatellite instability and apparently stable cancers were different in terms of tumour localisation (p=0.015), frequency of APC mutations (p=0.012), occurrence of Crohn's-like/lymphoid reaction (p=0.0353) and morphological evidence of origin from an adenoma (p=0.0338). Specifically, in low-frequency microsatellite instability cancers, APC mutations were very frequent (76.9%, 10/13) and a Crohn's-like/lymphoid reaction was common (38.5%, 5/13). High-frequency microsatellite instability tumours were preferentially located in the right colon and exhibited a higher frequency of loss of heterozygosity at the FHIT locus compared with low-frequency microsatellite instability and apparently stable cases (p=0.0243). Dukes' stage (p=0.0021), tumour localisation (p=0.0410) and pattern of cancer growth (p=0.0374), were the only factors affecting patient survival. However, a borderline improvement was noted in overall survival in high-frequency microsatellite instability and low-frequency microsatellite instability cancer patients (p=0.062). CONCLUSIONS: These results indicate that low-frequency microsatellite instability tumours have different genetics and histological features and suggest that they are a distinct group of colorectal cancers.
Adult↗
Mutations of the APC gene in human sporadic colorectal cancers.
BACKGROUND: Mutations of the APC gene are reported to occur frequently in sporadic colorectal adenomas and adenocarcinomas. We studied APC gene mutations in cases of human sporadic colorectal cancer in order to evaluate their correlation with pathologic characteristics and clinical prognosis. METHODS: Most of the mutations of the APC gene (95%) are nonsense or frame shift mutations, encoding for truncated APC proteins. For this reason, mutation detection of the APC gene was performed using the in vitro synthesized protein (IVSP) assay, analysing the region between nucleotide 2058 and nucleotide 5079 of the gene, containing the mutation cluster region. RESULTS: Out of 58 cases of colorectal cancer, 29 presented a mutated form of APC (mutation frequency 50%). We did not find a statistically significant correlation between APC gene mutation and age, sex, localization of the primary tumour, grading, Crohn-like lymphoid reaction or presence of residual adenoma. Tumours with low invasivity (Dukes' stages A and B) were less frequently mutated (12/27, 44.5%) than tumours of Dukes' stage C (15 out of 21, 71.4%), which developed macroscopically secondary metastasis with variable latency after surgery. Highly invasive tumours with synchronous metastases (Dukes' stage D) had, instead, a low frequency of APC mutations (20%, 2/10) (P = 0.02, compared with Dukes' stages A, B and C). CONCLUSIONS: These data suggest that more aggressive Dukes' stage D tumours develop metastasis by means of an unknown mechanism, independent of APC mutation.
Adenocarcinoma↗
Impairment of gastric secretion modulation in duodenal ulcer and in long-term PPI treatment: quantitative morphologic findings and pathophysiologic implications.
Helicobacter pylori affects gastric secretion. This functional effect might have a morphometric counterpart. Therefore, the gastric cell secretory compartment was morphometrically assessed in different pathophysiologic conditions related to Helicobacter pylori infection. Nineteen Helicobacter pylori-positive nonduodenal ulcer subjects, 15 omeprazole chronically treated subjects, and 19 duodenal ulcer patients were studied against 19 controls. Somatostatin, gastrin, enterochromaffin-like, and parietal cell density was assessed in gastric biopsies. No differences in any cell type density were found between Helicobacter pylori-positive nonduodenal ulcer subjects and controls. On the contrary, differences were significant when comparing omeprazole and duodenal ulcer patients to controls (higher density of gastrin, enterochromaffin-like, and parietal cells, lower density of somatostatin cells). In duodenal ulcer a reversion to control values followed Helicobacter pylori eradication and ulcer healing. A direct linear correlation between enterochromaffin-like, gastrin, and parietal cell density was demonstrated. An almost complete map of mucosal cells involved in gastric secretion is provided by this study. The cell density pattern, identical to the omeprazole group, points to an impaired feedback control of secretion in duodenal ulcer. The reversion to control values after Helicobacter pylori eradication and ulcer healing demonstrates the pathogenetic role of Helicobacter pylori-host interaction in these changes.
Adult↗
H(+),K(+)-atpase (proton pump) is the target autoantigen of Th1-type cytotoxic T cells in autoimmune gastritis.
BACKGROUND & AIMS: The proton pump H(+),K(+)-adenosine triphosphatase (H(+),K(+)-ATPase) of parietal cells is the major humoral autoantigen in both human and experimental autoimmune gastritis (AIG) characterized by an inflammatory infiltrate in the gastric mucosa and loss of parietal cells. The aim of this study was to detect H(+),K(+)-ATPase-specific T cells in the gastric mucosa of patients with AIG and to define their functional properties. METHODS: In vivo-activated T cells from the infiltrates of the gastric mucosa of 5 patients with AIG were isolated and cloned. The ability of gastric T-cell clones to proliferate and to produce cytokines in response to H(+),K(+)-ATPase, as well as their expression of B-cell help, perforin-mediated cytotoxicity, and Fas-Fas ligand-mediated apoptosis in target cells, were assessed. RESULTS: A proportion (25%) of the CD4(+) clones from the gastric corpus of AIG patients proliferated in response to porcine H(+),K(+)-ATPase. Most of these clones (88%) showed a Th1 profile, whereas a few secreted both Th1 and Th2 cytokines. Virtually all of the H(+),K(+)-ATPase-specific clones produced tumor necrosis factor alpha and provided substantial help for B-cell immunoglobulin production, and most of them expressed perforin-mediated cytotoxicity against antigen-presenting cells and induced Fas-Fas ligand-mediated apoptosis in target cells. CONCLUSIONS: Activation of proton pump-specific Th1 cytotoxic/proapoptotic T cells in the gastric mucosa can represent an effector mechanism for the target cell destruction in AIG.
Adult↗
Up-regulation of cyclooxygenase 2 gene expression correlates with tumor angiogenesis in human colorectal cancer.
BACKGROUND & AIMS: Recent studies have shown that cyclooxygenase (COX)-2 and its products, prostaglandins (PGs), may be involved in colorectal carcinogenesis. The aim of this study was to determine whether COX-2 expression and PGE(2) production correlate with microvessel density, vascular endothelial growth factor (VEGF) expression, and tumor metastasis in human colorectal cancer. METHODS: Tumor samples and adjacent normal mucosa were obtained from 31 surgical specimens. Immunohistochemical expression of COX-2, VEGF, and CD31 was analyzed on paraffin-embedded tissue sections. COX-2 and COX-1 proteins were determined by Western blot analysis. COX-2 and VEGF messenger RNA expressions were evaluated using Northern blot analysis. PGE(2) production was determined by specific radioimmunoassay. RESULTS: The immunohistochemical expressions of both COX-2 and VEGF were significantly correlated with microvessel density (P = 0.02 and P = 0.002, respectively). A significant correlation was found between COX-2 and VEGF expression (P = 0.004). Western analysis confirmed the up-regulation of COX-2 protein expression. COX-2 and VEGF genes were overexpressed in tumor specimens as compared with normal mucosa. PGE(2) levels were significantly higher in metastatic tumors than in nonmetastatic ones (P = 0.03). CONCLUSIONS: COX-2 is related to tumor angiogenesis in colorectal cancer. It is likely that VEGF is one of the most important mediators of the COX-2 angiogenic pathway.
Adenocarcinoma↗
[Somatostatin receptors in non-endocrine tumours].
The study of the antiproliferative action of somatostatin (ss) is important not only to understand the regulation of neuroendocrine tumours that express receptors (sst), but also non-endocrine tumours which express these receptors. We previously demonstrated the presence of sst2 in a wide panel of cell lines from human neuroblastoma. Although hypotheses have been put forward that treatment with ss or its analogs may be beneficial in oncological patients, this does not appear to be the case in neuroblastoma; patients with high sst2 levels (who are therefore sensitive to ss treatment) have per se a relatively positive outcome. Therefore, adjuvant treatment with ss is not necessary. Viceversa, patients with a poor prognosis are essentially characterized by a low expression of sst2 (and therefore are insensitive to a therapy with ss). In these patients adjuvant treatment with ss might be indicated, but would have little chance of success. Although the majority of neuroendocrine tumours expresses sst2, pancreas and prostate cancer express sst1 but not sst2, and are therefore insensitive to octreotide treatment which binds preferentially to sst2. Tumours like colorectal carcinoma and breast cancer also express sst2 in their more favourable forms. However, the concentration of sst2 in colorectal cancer is similar, if not lower than that in the surrounding normal tissue. Therefore, the probability of successful adjuvant therapy with ss is relatively low. In breast cancer, it is possible that sensitivity to estrogens may have a positive influence on the expression of sst2. This might justify clinical trials with ss in breast cancer.
Adenocarcinoma↗
Reflux and pH: 'alkaline' components are not neutralized by gastric pH variations.
The ability of the 'alkaline' components of reflux to cause harm in vivo is still open to debate, although these components have been shown in vitro to be capable of damaging the mucosa. The precipitation of bile acids and lysolecithin that occurs at low pH values is the main reason for questioning in vivo mucosal damage. This study was undertaken to determine the composition of gastric aspirates at different original pH values and the degree of solubility of the alkaline components when pH modifications are artificially induced. The samples for chemical analysis were collected from indwelling nasogastric tubes after surgical procedures that did not involve the upper gastrointestinal tract. Bile acid and lysolecithin concentrations were assessed by means of dedicated methods. Thirty-five samples were available for bile acid evaluation and 27 for lysolecithin evaluation. Bile acid and lysolecithin assessments were repeated after pH adjustment at 2, 3.5, 5.5 and 7. For easier assessment of the results, three ranges of the original pH were selected (pH < 2, 2 < or = pH < 5, pH > or = 5). For each pH range, results were pooled together and compared with those in the other pH ranges. Bile acid concentrations were 113+/-48, 339+/-90 and 900+/-303 (mean +/- s.e.m. micromol/L), respectively, in the three groups selected on account of the different original pH values. Differences were significant (p < 0.001). Both taurine- and glycine-conjugated bile acids were represented even at pH < 2. No major differences were observed in bile acid concentration with the artificially induced pH variations. Lysolecithin concentrations were 5.99+/-3.27, 30.80+/-8.43 and 108.37+/-22.17 (mean +/- SEM microg/ml), respectively, in the three groups selected on account of the different original pH ranges. Differences were significant (p < 0.001). No significant differences in lysolecithin concentration were detected with the artificially induced pH variations. In conclusion, both bile acids and lysolecithin are naturally represented in the gastric environment even at very low pH values, although their concentrations decrease on lowering of the naturally occurring pH. Given the concentration variability of bile acids and lysolecithin, further studies are needed to assess the minimal concentration capable of mucosal damage in vivo.
Bile Acids and Salts↗
Bcl-w expression in colorectal adenocarcinoma.
We have found that the anti-apoptotic Bcl-2 family protein, Bcl-w, was frequently expressed in colorectal adenocarcinomas, with 69/75 showing positive staining with anti-Bcl-w IgG. Adenomas demonstrated a much lower frequency of Bcl-w expression (only 1 of 17), as did adenocarcinomas from other epithelial tissues such as breast (0/8), stomach (1112) and cervix (0/12). Bcl-w status could be related to the histopathological classification of the tumours, with TNM stage III tumours showing significantly higher levels of expression than tumours of better prognostic grade (at P = 0.009). Those patients with node involvement also had tumours with significantly elevated levels of Bcl-w (at P = 0.02), compared to those which were node-negative. The results suggest that Bcl-w could play a general role in the progression from adenoma to adenocarcinoma in the colorectal epithelium. Currently, more data are being collected to allow us to assess the importance of Bcl-w for disease progression and patient survival.
Adenocarcinoma↗
Clinicopathologic features and FHIT gene expression in sporadic colorectal adenocarcinomas.
BACKGROUND: The putative tumour suppressor gene FHIT (fragile histidine triad) spans the common fragile site FRA3B, which is highly susceptible to breaks and deletions induced by genotoxic agents. Tumours associated with exposure to carcinogens, such as colorectal adenocarcinomas, should be particularly susceptible to alterations in the FHIT gene. We studied the frequency of FHIT alterations and their correlations with clinicopathologic features in sporadic colon carcinomas. METHODS: FHIT expression was investigated by reverse transcription polymerase chain reaction in 56 primary sporadic colorectal carcinomas. The same tumours and matched normal tissues were also investigated for loss of heterozygosity by using two markers located inside the FHIT gene. RESULTS: Twenty-nine of 56 tumours (51.8%) expressed aberrant FHIT transcripts. Four tumours had absence or nearly undetectable levels of the normal-sized FHIT transcript. Sequencing analysis of the altered transcripts showed FHIT mRNA lacking one or more exons, more frequent deletions of exons 4-5-6 or 4-5-6-7-8. At the genomic level 46.4% (13 of 28) of the cases showed alterations involving FHIT locus. We did not find any correlation between FHIT gene alterations and clinicopathologic characteristics of the tumours. CONCLUSIONS: Since the FHIT gene is frequently altered, its role in the molecular pathogenesis of sporadic colon carcinoma deserves further investigation.
Acid Anhydride Hydrolases↗
Analysis of the optical properties of bile.
Invasive bile determination is very useful in the diagnosis of many gastric pathologies. At the moment, this measurement is performed with Bilitec 2000, an optical fiber sensor, that is based on absorption by bilirubin. Nevertheless, erroneous evaluations are possible, due to the different configurations which the bilirubin molecule can adopt. The optical behavior of human samples of pure bile and bile+gastric juice has been examined using an optical fiber spectrophotometer and two suitably modified Bilitec 2000 units. A protocol has been established for the treatment of biological fluids, in order to make it possible to study the behavior of their optical properties as a function of pH and concentration without causing any alteration in the samples. The analysis of pH dependence evidenced the presence of different calibration curves at different pH values: the self-aggregation of the bilirubin molecules observed in pure bile samples was almost totally absent in the gastric samples. Measurements carried out on Bilitec 2000 showed that the most appropriate wavelength for bilirubin detection in the stomach should be 470 nm.
Bile↗
Correlation between DNA content and p53 deletion in colorectal cancer.
OBJECTIVE: To find out whether tumour DNA content correlates with allelic loss of p53 and other pathological features in primary colorectal carcinomas. DESIGN: Ongoing prospective study. SETTING: University hospital, Italy. SUBJECTS: 128 patients who had undergone radical resections for colorectal carcinoma. INTERVENTIONS: Flow cytometric measurement of tumour DNA content and detection of allelic loss on the short arm of chromosome 17 by Southern blot (restriction fragment length polymorphism) analysis in fresh tumour specimens. MAIN OUTCOME MEASURES: Correlation between DNA ploidy and deletion of p53, as well as between these two genetic events and clinicopathological variables. RESULTS: Interpretable DNA histograms were obtained for 122 tumour specimens. Forty-three tumours (35%) were diploid and 79 (65%) aneuploid. The diploid tumours were significantly more common in the proximal colon (from the caecum to the splenic flexure) than in the distal colon (from the descending colon to the rectum) (p = 0.002). The allelic state on the short arm of chromosome 17 was evaluated in 80 heterozygous patients. Forty-four tumour specimens (55%) showed deletion of 17p. Allelic loss of p53 was significantly more common in the distal and rectal tumours than in the proximal ones (p < 0.0001). Aneuploidy was more common among those tumours which had shown deletion of p53 than in those that had not (p = 0.0008). CONCLUSIONS: DNA aneuploidy was significantly associated with the deletion of the p53 gene. This suggests that the functional loss of p53 may favour the growth and establishment of an aneuploid cell population within tumours. Tumours of the proximal and distal colon differ in their genetic nature.
Adenocarcinoma↗
Marked variation of thymidylate synthase and folylpolyglutamate synthetase gene expression in human colorectal tumors.
Patients with advanced colorectal cancer are currently being treated with 5-fluorouracil (5-FU)-based chemotherapy. A growing number of patients with resectable disease receive adjuvant therapy with 5-FU/levamisole (LEV) or 5-FU/folinic acid (LV). However, many patients still fail on these treatments, due to occurrence of natural or acquired tumor resistance. Among clinically relevant mechanisms of resistance to fluoropyrimidines, increased expression of thymidylate synthase (TS) has been emphasized. Another potentially relevant mechanism involves a decrease in folylpolyglutamate synthetase (FPGS) expression. To establish the value of these genes as prognostic factors and predictors of the outcome of 5-FU-based chemotherapy in colorectal cancer, we measured their expression in colorectal tumors from patients undergoing surgery and postoperative chemotherapy and compared it with that in normal colonic mucosa. This was done by a semi quantitative, nonradioisotopic polymerase chain reaction (PCR) method using beta-actin as an internal standard and expressed as a TS/beta-actin or a FPGS/beta-actin mRNA ratio. In tumor samples from 21 colorectal cancer patients, TS gene expression varied 118-fold. The median TS/beta-actin ratio was, in fact, 41.36 x 10(-3) (range 2.49 x 10(-3) to 294.54 x 10(-3)). Little variation in TS gene expression was observed in corresponding normal colic mucosa; the TS/beta-actin gene ratio was lower (median 26.16 x 10(-3); range 8.49 x 10(-3) to 69.49 x 10(-3)). Among tumor explants from 20 patients, FPGS expression varied over 161-fold. A similar marked variation was also observed in normal colonic mucosal samples (over 185-fold). Overall and disease-free survival data suggest an inverse association between the level of tumor TS and FPGS expression and clinical prognosis. The availability of this sensitive and accurate assay for gene expression should now make it possible to extend these laboratory/clinical correlations to larger populations.
Adult↗
Pelvic floor dyssynergia and bimodal rehabilitation: results of combined pelviperineal kinesitherapy and biofeedback training.
Dyschezia may be caused by pelvic floor dyssynergia, which takes place when a paradoxical contraction or a failure to relax the pelvic floor muscles occurs during attempts to defecate. The aim of our study was to set up a new bimodal rehabilitation programme for pelvic floor dyssynergia, which combined pelviperineal kinesitherapy and biofeedback, and to evaluate the results of this treatment. Thirty-five patients (age range: 28-64 years; mean age: 42.5 years) from the outpatient unit of the Clinica Chirurgica of the University of Florence, Italy, and an age-matched group of 10 healthy control subjects (age range: 31-59 years; mean age 45.7 years) with normal bowel habits and without any defecatory disorders, were studied. The 35 patients were symptomatic for dyschezia without slow colonic transit and had been diagnosed as being affected by pelvic floor dyssynergia. No evidence of any organic aetiology was present but all demonstrated both manometric and radiological evidence of inappropriate function of the pelvic floor. All of the patients underwent bimodal rehabilitation, using the combined training programme Clinical evaluation, computerized anorectal manometry and defecography were carried out 1 week before and 1 week after a completed course in bimodal rehabilitation. The control group underwent manometric and defecographic examination. Their results were compared with those of the 35 patients before and after training. After the programme, all 35 patients had a very significant increase in stool frequency (P < 0.001), while laxative and enema-induced bowel movements had become significantly less frequent (P < 0.001). After bimodal rehabilitation, computerized anorectal manometry showed some peculiar results. Resting anal canal pressure had increased but not significantly. Pre-programme values that indicated a shorter duration ("exhaustio") of maximal voluntary contraction than found in the controls had returned to normal values. The rectoanal inhibitory reflex (RAIR), with incomplete relaxation, which had been shorter than that of controls, became normal by the end of the rehabilitation. All RAIR parameters were significantly different especially when pre- and post-treatment values were compared (P < 0.001). No differences were found as regards rectal sensation parameters and rectal compliance between those before or after bimodal rehabilitation. Defecographic pretreatment X-ray films showed indentation of the puborectalis and poor anorectal angle (ARA) opening, at evacuation, with trapping barium of at 50%. After pelviperineal kinesitherapy and biofeedback training, the indentation had disappeared and the ARA had become significantly larger (P < 0.001) during evacuation. No differences were found after rehabilitation, when both were compared with those of controls. The pelvic floor descent was also significantly deeper (P < 0.001) than before the start of the programme. The bimodal rehabilitation technique can be considered a useful therapeutic option for functional dyschezia as shown by our clinical evaluations, manometric data and defecographic reports.
Adult↗
Diagnostic value of preoperative DNA measurement on FNA in benign and malignant thyroid neoplasm.
Explore the source record for details and available documents.
Adenocarcinoma, Follicular↗
Character of the invasive margin in colorectal cancer: does it improve prognostic information of Dukes staging?
PURPOSE: The clinical significance and prognostic value of the histopathologic parameters used in both the Dukes and Jass classifications were evaluated to select those with an independent effect on survival after radical surgery for colorectal cancer. METHODS: The depth of local spread (limited to the bowel wall or extended beyond it), the number of metastatic lymph nodes (none, 1-4, more than 4), the character of the invasive margin (pushing or infiltrating), and the presence or absence of conspicuous peritumoral lymphocytic infiltration were assessed in 235 patients who had undergone radical resection for colorectal cancer. The influence of these variables on survival was studied by univariate and multivariate analysis. RESULTS: No significant difference in survival was found between patients with conspicuous peritumoral infiltrate and those without it; moreover, multivariate analysis failed to show any independent prognostic value for either lymphocytic infiltration or depth of local invasion. However, the character of the invasive margin and the number of metastatic lymph nodes were identified as the only variables with any independent importance on survival. Based on these data, a new prognostic model may be proposed; it uses the character of the infiltrative margin as a discriminating factor among patients within the lymph node-negative (Dukes A and B stages) and lymph node-positive (Dukes C1 and C2 subsets) groups. A good prognosis for Dukes A, B, and C1 patients was associated with pushing tumors; C1 and C2 patients with infiltrating tumors had a poor prognosis. On the whole, the new prognostic model has allowed for the placement of 59.6 percent of our patients into groups that provide a confident prognosis. The clinical outcome of Dukes A and B patients with infiltrating tumors is still uncertain. CONCLUSIONS: The character of the invasive margin is an important prognostic factor in colorectal cancer. The association of this parameter with the traditional Dukes classification may provide additional useful prognostic information and aid in the selection of those patients who could most benefit from adjuvant therapy.
Adenocarcinoma↗