Proportional incidence of interval colorectal cancer in a large population-based faecal immunochemical test screening programme.

BACKGROUND: The European guidelines for quality assurance in colorectal cancer (CRC) screening recommend that interval cancer rate be expressed as a proportion of background incidence rate. AIM: To determine the crude and adjusted proportional incidence of interval CRC in an Italian regional two-yearly faecal immunochemical test (FIT) screening programme. METHODS: The programme (year of implementation, 2005) is targeted at over 1,000,000 people aged 50-69 years. The test is a one-sample OC-Sensor (Eiken Chemical Co., Tokyo, Japan). The study covered one-third of the regional area. Excerpts of 434,295 eligible negative FIT records dated 2005-2012 from 193,193 subjects were retrieved from the regional CRC screening data warehouse. By 31 December 2013, the cohort accumulated 198,302 man-years and 235,370 woman-years. Interval CRCs were identified by record-linkage with the local population-based cancer registry. Their number was divided by the expected number, estimated with age-period-cohort models, to obtain the proportional incidence. RESULTS: The proportional incidence of interval CRC for men and women was, respectively, 0.06 (95% confidence interval (CI), 0.04-0.09) and 0.17 (95% CI, 0.13-0.23) in the first interval year, and 0.21 (95% CI, 0.16-0.26) and 0.28 (95% CI, 0.22-0.36) in the second year. CONCLUSIONS: The results were acceptable and in line with previous studies.

Preparation for colonoscopy: Recommendations by an expert panel in Italy.

BACKGROUND: Despite several guidelines on bowel preparation being available, their applicability in Italy is poorly investigated. AIMS: (1) To create expert-based recommendations for the Italian setting based on available international guidelines on bowel preparation for colonoscopy; (2) to assess consensus across the Italian endoscopy community. METHODS: The study was conducted in 2 phases: (a) statements formulation, (b) assessment of consensus. For the first phase, 6 topics related to bowel preparation were identified: (1) efficacy/tolerability; (2) timing; (3) assessment of quality of bowel preparation; (4) factors associated with inadequate preparation; (5) patient education and (6) impact of organisational factors. For each topic, statements were produced and voted by a panel of experts. For consensus assessment, the invited participants were asked to rate the statements. The statement achieved a good level of agreement when at least 70% of voters agreed with it. RESULTS: 25 statements were agreed in the first phase. Agreement was not achieved by the endoscopy community for 7 statements, mainly concerning practical aspects (i.e. strategies for management of patients with inadequate preparation, organisational factors). CONCLUSION: A clinically relevant consensus was achieved on the main topics of bowel preparation, such as the choice of laxative and the time of administration, and it may help to homogenize the colonoscopy practice in Italy. Nevertheless, there are a few country-specific preparation-related issues that need to be addressed.

A model of an inflammatory bowel disease population-based registry: The Forlì experience (1993-2013).

BACKGROUND AND AIMS: The article presents a population-based registry designed to estimate incidence and prevalence of inflammatory bowel disease (IBD) in the area of Forlì (north-eastern Italy). METHODS: The registry included all patients with IBD ulcerative colitis (UC) and Crohn's disease (CD) in the Forlì area from 1993 to 2013. A data manager matched records from various sources. RESULTS: Seven hundred ninety-one patients were registered during the study period, 564 (71.3%) with UC and 227 (28.7%) with CD. The standardized annual incidence rate for UC was 12.8 per 100,000 females (95% CI 11.1-14.4) and 15.7 per 100,000 males (95% CI 13.9-17.5). That of CD was 7.0 per 100,000 for females (95% CI 5.7-8.3) and 5.4 per 100,000 males (95% CI 4.3-6.4). The prevalence of CD and UC on 1 January 2014 was 109.2 per 100,000 inhabitants (95% CI 94.3-124.2) and 266.4 per 100,000 inhabitants (95% CI 243.4-289.7), respectively. CONCLUSIONS: Although further studies are needed, the data suggest that incidence and prevalence of IBD in Italy are underestimated.

Inter-centre variability of the adenoma detection rate: a prospective, multicentre study.

BACKGROUND: Suboptimal colonoscopy quality is related to a higher risk of interval cancer. Aim of our study was to explore the variability in detection rate of neoplasia among different endoscopic centres in an unselected population. METHODS: Consecutive patients referred for colonoscopy in 28 Italian centres were included. Detection rate for polyp, neoplasia and advanced neoplasia was assessed at both the individual and centre level. Inter-centre variability in detection rate of colorectal lesions was explored after adjusting for patient-related factors at multivariate analysis. RESULTS: 3150 patients were included. Median detection rates for polyp, neoplasia and advanced neoplasia were 35%, 26% and 13%. At multivariate analysis, patient-related factors associated with neoplasia detection were age, sex, alcohol and smoking history. After adjusting for these variables, a statistically significant difference in the observed/expected ratio among different centres was observed (Chi-squared test: p<0.01). Among non-patient-related factors, documentation of withdrawal time was associated with neoplasia detection. However, a statistically significant inter-centre variability also remained after adjusting for this variable. CONCLUSIONS: A wide variability was present in the detection rate of neoplasia and advanced neoplasia at the level of endoscopic centres in an unselected population. The adoption of a centre-related neoplasia detection rate could be suggested as a performance indicator.

Massively calcified intravascular cast after removal of a tunneled central vein catheter for hemodialysis.

Vascular calcifications usually affect the arteries, while central vein calcifications are rare. A 45-year-old hemodialysis patient underwent a chest CT scan before central vein catheterization required for arteriovenous access thrombosis, in July 2011. He was on hemodialysis since 1995 and from 2005 on warfarin treatment because of repeated thrombosis and dysfunction of arteriovenous fistula and central vein catheters (CVC). A previous tunneled CVC placed in the left external jugular vein was removed in December 2010. Eight months later a chest CT scan showed a 79-mm irregular, linear, tubular radiopaque density in the superior vena cava and left brachiocephalic vein. The possibility of a retained catheter fragment was considered, but the final diagnosis was: calcified "cast" adherent to the vessel wall. This is the first report of an intravenous calcified "cast" (originating from peri-catheter calcification) retained after removal of a tunneled dialysis CVC. This finding is significant because it mimics a retained catheter fragment possibly leading to misdiagnosis and exposing patients to additional risk for unnecessary retrieving interventions. Catheter removal or over the wire substitution in the presence of a calcified cast could also be considered a risky procedure. Retained calcified cast should be included among the long-term complications of hemodialysis CVCs. At the time of publication, the patient is alive without any complication related to the pathology reported.

Rescue endoscopy to identify site of gastric dysplasia or carcinoma found at random biopsies.

BACKGROUND: Incidental findings of high-grade dysplasia or gastric cancer at random biopsies with endoscopic diagnosis of chronic gastritis constitute a serious problem to clinical management of patients and sometimes requires blind gastrectomy. AIM: To evaluate diagnostic value of second-look endoscopy, called "rescue endoscopy", in order to identify focal lesions containing neoplastic changes. METHODS: Over a three-year period, 20 patients underwent rescue endoscopy using advanced endoscopy and mapping technique. All mucosal irregularities were identified and the locations of these areas were mapped onto a schematic diagram of gastric anatomy. Each area was biopsied and samples included in individually marked specimen containers, to evaluate the correlation between macroscopic and microscopic diagnosis. RESULTS: Rescue endoscopy identified a total of 68 focal lesions, 18 of which were focal areas of high-grade dysplasia (13 patients) or gastric cancer (5 patients). Two patients had no dysplastic change identified by our targeted biopsies. A second pathologist's opinion confirmed absence of dysplasia on random and targeted biopsies. All patients underwent a median follow-up of 15.2 months (2.6-43.5), and no residual or metachronous lesions were identified. CONCLUSIONS: In our experience, rescue endoscopy is highly effective in localizing undetermined areas of high-grade dysplasia or carcinoma.

Nutrient intake in Italian obese patients: relationships with insulin resistance and markers of non-alcoholic fatty liver disease.

OBJECTIVE: We investigated the prevalence of insulin resistance, elevated liver enzymes, and Non-Alcoholic Fatty Liver Disease Fibrosis Score (NFS) in obese and severely obese patients. Relations between inadequate nutrient intakes and the markers of metabolic and hepatic disorders were evaluated. METHODS: From January to September 2009, 63 consecutive obese patients (21 men and 42 women, 19-68 y old) were admitted to the study. According to the World Health Organization obesity classification, patients were categorized into three subgroups (classes I, II, and III). NFS scores lower than -1.455 were defined as NFS(-); higher scores were positive (NFS(+)). Insulin resistance (IR) was assessed by the homeostasis model assessment. Nutrient intakes and their potential role as risk factors for IR and liver damage were determined. RESULTS: Body mass index ranged from 30.9 to 73.7 kg/m(2) and most patients (54%) were in class III (body mass index ≥40 kg/m(2)). Homeostasis model assessment of IR (>2.5) was recorded in 63.5%. The prevalence of NFS(+) was significantly higher in class III than in classes II and I. Excessive nutrient and energy intake prevalence showed significant differences for protein, fat, and carbohydrate among the obesity classes. Animal protein (odds ratio 3.43, 95% confidence interval 1.15-10.20) and carbohydrate (odds ratio 3.83, 95% confidence interval 1.33-10.94) intakes were the risk factors for IR and NFS(+). CONCLUSION: Non-normal alanine aminotransferase and γ-glutamyltranspeptidase values were observed in less than one-third of patients, whereas NFS(+) and IR were significantly prevalent, suggesting a close relation between the progression of liver fibrosis and metabolic derangement. An excessive intake of animal protein is associated with an increased risk of IR. Carbohydrate intake, albeit at the highest limit of the recommended dietary allowance range, is associated with an increased risk of liver fibrosis.

Quantitative fluorescence determination of long-fragment DNA in stool as a marker for the early detection of colorectal cancer.

BACKGROUND: A variety of molecular markers have been evaluated for the development of a non-invasive approach to the diagnosis of colorectal cancer. We aimed to validate the diagnostic accuracy, using the same threshold as in the previous pilot study, of fluorescent long DNA test as a relatively simple and inexpensive tool for colorectal cancer detection. METHODS: A case-control study was conducted on 100 healthy subjects and 100 patients at first diagnosis of colorectal cancer. Human long-fragment DNA in stool was quantified by fluorescence primers and a standard curve and expressed in DNA nanograms. RESULTS: We validated the 25-ng value, which emerged as the most accurate cut-off in the pilot study, obtaining 79% (95% CI, 71-87%) sensitivity and 89% (95% CI, 83-95%) specificity. Specificity was very high for all cut-off values (15-40 ng) analyzed, ranging from 78 to 96%. Sensitivity was only slightly lower, reaching 84% at the lowest cut-off and maintaining a good level at the higher values. Diagnostic potential was independent of gender, age and tumor site. CONCLUSION: Fecal DNA analysis is a non-invasive and fairly simple test showing high diagnostic potential. These characteristics, together with the small amount of stool required, make it potentially suitable to be used alongside or as an alternative to current non-invasive screening approaches. Our next step will be to validate these results in a large-scale cohort study of a screening population, which is needed prior to implementation into clinical practice.

Stent migration as a late complication following carotid angioplasty and stenting.

BACKGROUND: A 69-year-old male patient with severe asymptomatic carotid artery stenosis was treated percutaneously with implant of two self-expandable stents in the right carotid overlapped to each other by 5 mm. The 15-month follow-up colour-Doppler ultrasound (CDU) revealed a severe stenosis in the target vessel and an image suggesting migration of the distal stent. INVESTIGATIONS: Physical examination, laboratory test, CDU, carotid angiography, quantitative carotid angiography (QCA), brain computed tomography (CT). DIAGNOSIS: Migration of the distal stent associated with severe stenosis on the unsupported arterial segment. MANAGEMENT: Carotid artery angiography, QCA, antithrombotic therapy, carotid artery angioplasty and stenting (CAS).

Receptor activator of nuclear factor kappa B ligand (RANKL) modulates the expression of genes involved in apoptosis and cell cycle in human osteoclasts.

It has been clearly established that receptor activator of nuclear factor kappa B ligand (RANKL) is a key cytokine involved in the differentiation of osteoclastic precursors of the monocytic/macrophagic lineage. However, relatively little information is available on the ability of RANKL to modulate the expression of genes controlling cell survival/apoptosis and proliferation in human osteoclastic cells in comparison to macrophages. For this purpose, CD14+ human peripheral blood mononuclear cells, which express the cognate high affinity receptor activator of nuclear factor kappa B (RANK), were differentiated along the macrophagic or osteoclastic lineage by adding macrophage-colony stimulating factor (M-CSF) or M-CSF plus RANKL in culture for 12 days. RANKL up-regulated the expression of the chemokine MIP1alpha, which potentiates osteoclastic differentiation and simultaneously activated both anti-apoptotic (Bcl-2) and pro-apoptotic (CIDEB, PYCARD, and BAK-1) genes. Moreover, RANKL markedly up-regulated cylin D2, while it significantly decreased the levels of cyclin A, cyclin-dependent kinase 2, and other cyclin-dependent kinases, in keeping with the notion that end-stage osteoclasts are nondividing cells. Finally, a long-term exposure of RANKL up-regulated the adaptor protein TRAF3 but not TRAF6.

Endovascular treatment of soft carotid plaques: a single-center carotid stent experience.

PURPOSE: To report a prospective evaluation of the 30-day clinical neurological outcome in patients percutaneously treated for severe symptomatic and asymptomatic soft echolucent carotid plaques under cerebral protection from a proximal flow blockade system. METHODS: From December 2001 to February 2005, 84 consecutive patients (63 men; mean age 70.7 +/- 7.1 years, range 58-81) with documented soft echolucent (gray scale median < 25) extracranial carotid lesions were enrolled in a study of percutaneous stenting under cerebral protection achieved by a proximal endovascular clamping device. Primary endpoint of the study was the all stroke and death rate at 30 days. Secondary endpoints were angiographic success and any complication between discharge and 30 days. All adverse events were analyzed by an independent neurological team. RESULTS: Total neurological events at 30-day follow-up included 3 transient ischemic attacks and 1 minor stroke (4.8% neurological event rate). The 30-day rates of stroke and neurological death/stroke were both 1.2%; the all death/stroke rate was 2.4%. Clamping intolerance was observed in 5.9% of cases, but there was no interruption in the procedure or clinical sequelae. In 66.7% of patients, visible debris was collected during the procedure. CONCLUSION: Protected CAS with proximal flow blockage can successfully be applied in selected patients for soft carotid plaques at high risk for intraprocedural embolic events.

Validation of a new non-invasive portable tonometer for determining arterial pressure wave and pulse wave velocity: the PulsePen device.

OBJECTIVE: To validate a new, small portable tonometer (PulsePen) that is able to assess carotid artery pressure and to measure pulse wave velocity (PWV) non-invasively. Its software provides absolute arterial pressure values, an assessment of arterial pulse wave contours, an estimation of reflection waves and measurements of PWV. DESIGN AND METHODS: Two validation studies were carried out. The aim of the first study was to compare arterial pressure values and pulse wave contours recorded in the carotid artery using the PulsePen versus intra-arterial simultaneous measurements in 10 patients undergoing cardiac catheterization. The pulse wave contour was assessed using Fourier analysis. The comparison between the two methods showed no difference in arterial pressure wave spectral moduli from harmonics 1 to 6. The second study compared PWV measurements taken with the PulsePen (one tonometer) and measurements performed with two Millar tonometers in 68 subjects (32 men, 36 women). PulsePen measurements were realized as two consecutive measurements in the carotid and femoral arteries, both synchronized by electrocardiogram. The pulse wave transit time was calculated as the difference between the time delay of the femoral pulse wave and the carotid pulse wave in relation to the R wave of the electrocardiogram. These measurements were compared with PWV obtained by simultaneous carotid and femoral measurements with the two Millar tonometers. No difference between the two methods was found, with a variation coefficient of 7.7%. The variation coefficients of the inter-observer and intra-observer reproducibility for the PulsePen were 7.9 and 7.2%, respectively. CONCLUSIONS: These results show that the PulsePen enables an easy and reliable evaluation of central arterial pressure and stiffness in clinical ambulatory practice, especially in high-risk patients in whom arterial stiffness has been shown to be a significant indicator of morbidity and mortality.

Impact of cerebral protection devices on early outcome of carotid stenting.

PURPOSE: To evaluate the impact of cerebral protection devices on the procedural safety and outcome of carotid stent procedures. METHODS: From June 1997 to July 2001, 275 consecutive patients (208 men; mean age 71 +/- 7.4 years) underwent percutaneous angioplasty and/or stenting of the extracranial carotid artery. In the first 125 (45.4%) patients, the procedures were performed without cerebral protection. After January 2000, protection devices were routinely used (150 [54.6%] patients), including the Angioguard filter, GuardWire occlusion system, TRAP Vascular Filtration System, EPI Filter Wire, NeuroShield, Parodi Anti-Embolism System, and Medicorp occlusive balloon. RESULTS: The percutaneous procedures were effective in 273 (99.3%) patients. No death or major stroke occurred in either group. In the unprotected group, 5 (4.0%) complications occurred: 3 (2.4%) minor strokes, 1 (0.8%) transient ischemic attack (TIA), and 1 (0.8%) subarachnoid hemorrhage. In the patients treated under cerebral protection, there were 2 (1.3%) complications: 1 (0.7%) minor stroke and 1 (0.7%) subarachnoid hemorrhage. There were 4 (3.2%) periprocedural embolic complications in the unprotected group versus 1 (0.7%) in the protected patients. CONCLUSIONS: Our data suggest that percutaneous dilation and stenting of the carotid arteries protected by cerebral protection devices is feasible and effective. In a consecutive series, the use of the cerebral protection systems reduced the acute neurological event rate related to embolic complications by 79%.