[show abstract][hide abstract] ABSTRACT: Although leiomyomas of the stomach or small intestine are relatively common, those of the colon or rectum are rare. Several cases of endoscopic resection of colorectal leiomyomas have been described. However, conventional polypectomy of leiomyomas can result in perforation. To reduce the risk of perforation, submucosal injection can be performed before removal. We report a case of chronic sideropenic anaemia in a patient affected by leiomyoma of the sigmoid colon in which after complete endoscopic enucleation of the lesion we obtained the stable resolution of anaemia.
[show abstract][hide abstract] ABSTRACT: We have previously shown that serum/glucocorticoid regulated kinase 1 (SGK1) is down-regulated in colorectal cancers (CRC) with respect to normal tissue. As hyper-methylation of promoter regions is a well-known mechanism of gene silencing in cancer, we tested whether the SGK1 promoter region was methylated in colonic tumour samples.
We investigated the methylation profile of the two CpG islands present in the promoter region of SGK1 in a panel of 5 colorectal cancer cell lines by sequencing clones of bisulphite-treated DNA samples. We further confirmed our findings in a panel of 10 normal and 10 tumour colonic tissue samples of human origin. We observed CpG methylation only in the smaller and more distal CpG island in the promoter region of SGK1 in both normal and tumour samples of colonic origin. We further identified a single nucleotide polymorphism (SNP, rs1743963) which affects methylation of the corresponding CpG.
Our results show that even though partial methylation of the promoter region of SGK1 is present, this does not account for the different expression levels seen between normal and tumour tissue.
PLoS ONE 01/2010; 5(11):e13840. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: Colorectal cancers are believed to arise predominantly from adenomas. Although these precancerous lesions have been subjected to extensive clinical, pathologic, and molecular analyses, little is currently known about the global gene expression changes accompanying their formation. To characterize the molecular processes underlying the transformation of normal colonic epithelium, we compared the transcriptomes of 32 prospectively collected adenomas with those of normal mucosa from the same individuals. Important differences emerged not only between the expression profiles of normal and adenomatous tissues but also between those of small and large adenomas. A key feature of the transformation process was the remodeling of the Wnt pathway reflected in patent overexpression and underexpression of 78 known components of this signaling cascade. The expression of 19 Wnt targets was closely correlated with clear up-regulation of KIAA1199, whose function is currently unknown. In normal mucosa, KIAA1199 expression was confined to cells in the lower portion of intestinal crypts, where Wnt signaling is physiologically active, but it was markedly increased in all adenomas, where it was expressed in most of the epithelial cells, and in colon cancer cell lines, it was markedly reduced by inactivation of the beta-catenin/T-cell factor(s) transcription complex, the pivotal mediator of Wnt signaling. Our transcriptomic profiles of normal colonic mucosa and colorectal adenomas shed new light on the early stages of colorectal tumorigenesis and identified KIAA1199 as a novel target of the Wnt signaling pathway and a putative marker of colorectal adenomatous transformation.
Molecular Cancer Research 01/2008; 5(12):1263-75. · 4.35 Impact Factor
[show abstract][hide abstract] ABSTRACT: In colorectal cancer, activating mutations in the Wnt pathway transform epithelial cells through the inappropriate expression of a TCF4 target gene program, which is physiologically expressed in intestinal crypts.
We have now performed an exhaustive array-based analysis of this target gene program in colorectal cancer cell lines carrying an inducible block of the Wnt cascade. Independently, differential gene-expression profiles of human adenomas and adenocarcinomas vs normal colonic epithelium were obtained.
Expression analyses of approximately 80 genes common between these data sets were performed in a murine adenoma model. The combined data sets describe a core target gene program, the intestinal Wnt/TCF signature gene set, which is responsible for the transformation of human intestinal epithelial cells.
The genes were invariably expressed in adenomas, yet could be subdivided into 3 modules, based on expression in distinct crypt compartments. A module of 17 genes was specifically expressed at the position of the crypt stem cell.
[show abstract][hide abstract] ABSTRACT: Perforation is one of the most serious complications of endoscopic sphincterotomy. In the last decade, the management has shifted towards a more selective approach. Three cases are reported here involving three different treatments. In one case, the patient was submitted to a surgical procedure, while a conservative strategy was preferred in the other two, consisting in a naso-biliary drain and endoscopic clip placement, respectively. In this way, the safety of surgical and nonsurgical management of ERCP-related duodenal perforations was tested.
[show abstract][hide abstract] ABSTRACT: The very rare case of a non-cirrhotic patient with multiple intrahepatic portosystemic and arteriosystemic vascular shunts, presenting with hyperammoniaemic type B encephalopathy and hypoalbuminaemia due to proteinuria, is reported. The correct diagnosis, suspected by abdominal ultrasound and colour-Doppler imaging, was confirmed by hepatic and superior mesenteric angiography. A comparison with the few similar cases existing in the literature is offered.
Digestive and Liver Disease 06/2006; 38(5):347-51. · 3.16 Impact Factor
[show abstract][hide abstract] ABSTRACT: Because hepatic cirrhosis is a major risk factor for hepatocellular carcinoma, recent guidelines by the European Association for the Study of the Liver (EASL) on clinical management of hepatocellular carcinoma recommend periodic ultrasound surveillance of cirrhotic patients with immediate workup for nodules >1 cm; an increase in the frequency of screening is considered sufficient for smaller lesions.
To determine the actual risk of hepatocellular carcinoma associated with the latter lesions and to assess the role of ultrasound guided-fine needle biopsy in their diagnosis.
Data were analysed for 294 new nodular lesions <20 mm, including 48 that were <10 mm, detected during a prospective multicentre study involving ultrasound surveillance of 4375 patients with hepatic cirrhosis. In the absence of alpha fetoprotein (AFP) levels diagnostic of hepatocellular carcinoma, ultrasound guided-fine needle biopsy was performed (n = 274). AFP and fine needle biopsy diagnoses of malignancies (hepatocellular carcinoma and lymphoma) were considered definitive. Non-malignant fine needle biopsy diagnoses (dysplastic or regenerative nodule) were verified by a second imaging study. Diagnoses of hepatocellular carcinoma based on this study were considered definitive; non-malignant imaging diagnoses were considered definitive after at least one year of clinical and ultrasound follow up.
Overall, 258/294 (87.6%) nodules proved to be hepatocellular carcinoma, including 33/48 (68.7%) of those < or =10 mm. Overall typing accuracy of ultrasound guided-fine needle biopsy was 89.4%, and 88.6% for lesions < or =10 mm.
In a screening population, well over half of very small nodules arising in cirrhotic livers may prove to be hepatocellular carcinoma, and approximately 90% of these malignancies can be reliably identified with ultrasound guided-fine needle biopsy.
[show abstract][hide abstract] ABSTRACT: Guided biopsy of hepatocellular carcinoma has been recently discussed again due to the progress of imaging techniques and the risk of malignant seeding after the procedure. Ultrasound is probably still the most accurate imaging modality for early detection of nodules arising on cirrhosis, even when compared with more advanced imaging techniques. It can be easily employed in the surveillance of high-risk cirrhotic patients. Ultrasound-guided biopsy has very high sensitivity and almost absolute specificity, which allows the appropriate treatment to start after a positive diagnosis. It also allows correct diagnosis of lymphomatous nodules, the incidence of which is increased in hepatitis C virus-related cirrhosis. The risk of seeding appears limited according to the currently available epidemiological data; this should be considered against the risk of false-positive diagnosis of malignancy based on imaging studies alone. Ultrasound-guided biopsy is a valuable tool also for the diagnosis of small nodules (less than 10 mm in diameter). The best accuracy in the sampling of hepatocellular carcinoma nodules is obtained by combining smear cytology and microhistology. This can be achieved by a single biopsy with a fine cutting needle that furnishes pathologic material suitable for both examinations, reducing risks and costs.
[show abstract][hide abstract] ABSTRACT: Hereditary nonpolyposis colorectal cancer (HNPCC) is frequently associated with constitutional mutations in a class of genes involved in DNA mismatch repair. We identified 32 kindreds, with germline mutations in one of three genes hMSH2, hMLH1 or hMSH6. In this study, we purposed to evaluate how many high-risk individuals in each family underwent genetic testing: moreover, we assessed how many mutation-positive unaffected individuals accepted colonoscopic surveillance and the main findings of the recommended follow-up. Families were identified through a population-based registry, or referred from other centres. Members of the families were invited for an education session with two members of the staff. When a kindred was consistent with HNPCC, neoplastic tissues were examined for microsatellite instability (MSI) and immunohistochemical expression of MSH2, MLH1 and MSH6 proteins. Moreover, constitutional mutations were searched by SSCP or direct sequencing of the whole genomic region. Of the 164 subjects assessed by genetic testing, 89 were gene carriers (66 affected - that is, with HNPCC-related cancer diagnosis - and 23 unaffected) and 75 tested negative. Among the 23 unaffected gene carriers, 18 (78.3%) underwent colonoscopy and four declined. On a total of 292 first degree at risk of cancer, 194 (66.4%) did not undergo genetic testing. The main reasons for this were: (a) difficulty to reach family members at risk, (b) lack of collaboration, (c) lack of interest in preventive medicine or 'fatalistic' attitude towards cancer occurrence. The number of colorectal lesions detected at endoscopy in gene carriers was significantly (P<0.01) higher than in controls (noncarriers). We conclude that a large fraction of high-risk individuals in mutation-positive HNPCC families does not undergo genetic testing, despite the benefits of molecular screening and endoscopic surveillance. This clearly indicates that there are still barriers to genetic testing in HNPCC, and that we are unable to provide adequate protection against cancer development in these families.
British Journal of Cancer 02/2004; 90(4):882-7. · 5.08 Impact Factor
[show abstract][hide abstract] ABSTRACT: Functional dyspepsia is a major problem in terms of prevalence and drug-therapy expenditures. In dyspeptic patients the symptoms are frequently caused by delayed gastric emptying. Conventional treatment is often inefficient. Mineral-water supplementation is prescribed for the treatment of this condition, but there is no concrete proof of its actual efficacy. The aim of this study was to evaluate the effect of supplementation with mineral waters with high mineral salt contents (Acqua Tettuccio, Acqua Regina, Montecatini Terme) on gastric emptying of solids and symptoms in patients with functional dyspepsia.
Eight patients with functional dyspepsia and two healthy (non-dyspeptic) controls were placed on high-mineral-content water supplementation (500 cc/day) for eight days. Before and after completion of the supplementation treatment, patient symptoms were scored and the 13C-octanoic-acid breath test was administered to assess gastric emptying.
After the treatment, the dyspeptic subjects presented clear decreases in parameters of gastric emptying (half time and lag time) as well as an improvement in symptom scores.
Health spa treatments based on consumption of waters with a high content of mineral salts seem to be capable of improving gastric emptying of solids in dyspeptics. Longer and longitudinal studies are needed to verify the persistence of this effect.
[show abstract][hide abstract] ABSTRACT: Current noninvasive tests to confirm the eradication of Helicobacter pylori must be performed 4 weeks or more after eradication therapy is completed.
To determine whether the stool antigen test, a relatively new noninvasive test for H. pylori, administered at various times after eradication therapy correctly identifies persons with persistent H. pylori infection.
Prospective blinded study.
Six clinical centers in the United States and Europe.
84 H. pylori --infected patients undergoing endoscopy for upper abdominal symptoms.
At baseline and on day 35 after the completion of triple eradication therapy, all patients underwent endoscopy with histologic examination, rapid urease test and culture, urea breath test, and a stool antigen test. The stool antigen test was also performed on days 3, 7, 15, 21, 28, and 35 after completion of therapy.
Compared with the gold-standard endoscopic tests on day 35 after antimicrobial therapy, the urea breath test had a sensitivity of 94% (95% CI, 71% to 100%) and a specificity of 100% (CI, 94% to 100%). The stool antigen test had a sensitivity of 94% (CI, 71% to 100%) and a specificity of 97% (CI, 89% to 100%). On day 7 after treatment, the stool antigen test was predictive of eradication (positive predictive value, 100% [CI, 69% to 100%]; negative predictive value, 91% [CI, 82% to 97%]).
A positive result on the stool antigen test 7 days after completion of therapy identifies patients in whom eradication of H. pylori was unsuccessful.
Annals of internal medicine 03/2002; 136(4):280-7. · 13.98 Impact Factor
[show abstract][hide abstract] ABSTRACT: About 15%-20% of colorectal cancers (CRCs) are familial. While a fraction of these arise in the context of hereditary syndromes, the causes underlying the majority of familial CRCs are not yet understood.
Family history of cancer, clinical characteristics, and microsatellite instability (MSI) in a series of 100 consecutive CRC patients were evaluated.
Eighteen patients had a positive family history of CRC in a first-degree relative. Of these, two had a clinical diagnosis of familial adenomatous polyposis (FAP), and three were diagnosed with hereditary non-polyposis colorectal cancer (HNPCC) following results of MSI analysis. A diagnosis of HNPCC was also established in a fourth patient with early onset CRC, who had a second-degree relative with CRC, and whose tumor was positive for MSI. The remaining 13 familial CRCs did not show MSI in tumor DNA. The mean age at tumor diagnosis in patients with familial microsatellite-stable (MSS) CRC was higher than in HNPCC and FAP patients and similar to that recorded in sporadic cases. The incidence of second primary malignancies was significantly higher in familial MSS CRC probands (n = 4) compared to patients who did not have a diagnosis of FAP or HNPCC and did not have first-degree relatives affected with CRC (n = 6, in a total of 81 probands with these characteristics).
These results define the existence of a subset of familial CRCs characterized by relatively late age at onset, high incidence of second primary tumors, and absence of MSI in tumor DNA.
Annals of Oncology 07/2001; 12(6):813-8. · 7.38 Impact Factor
[show abstract][hide abstract] ABSTRACT: One-week triple therapy is currently considered the golden standard against Helicobacter pylori. However, gastrointestinal side-effects are among the major pitfalls in such regimens. Probiotic supplementation might help to prevent or reduce such drug-related manifestations.
To determine whether adding the probiotic Lactobacillus GG to an anti-H. pylori regimen could help to prevent or minimize the gastrointestinal side-effects burden.
Sixty healthy asymptomatic subjects screened positive for H. pylori infection were randomized to 1 week rabeprazole (20 mg b.d.), clarithromycin (500 mg b.d.), tinidazole (500 b.d.) and the probiotic Lactobacillus GG for 14 days or to the same regimen with a placebo preparation. Patients completed validated questionnaires during the week of treatment and during the following 3 weeks, to determine the type and severity of side-effects and an overall judgement of tolerability.
Diarrhoea, nausea and taste disturbance were significantly reduced in the Lactobacillus GG supplemented group (relative risk=0.1, 95% CI: 0.1-0.9; relative risk=0.3, 95% CI: 0.1-0.9; relative risk=0.5, 95% CI: 0.2-0.9, respectively). An overall assessment of treatment tolerability showed a significant difference in favour of the Lactobacillus GG supplemented group (P=0.04).
Lactobacillus GG supplementation showed a positive impact on H. pylori therapy-related side-effects and on overall treatment tolerability.