Advanced urothelial cancer: a radiology update.

The recent genomic characterization of urothelial carcinoma by the Cancer Genome Atlas Project, made possible by the introduction of high throughput, reduced cost, and sequence analysis, has shed new insights on the biology of advanced disease. In addition, studies on imaging of advanced urothelial carcinoma have widened the knowledge on disease presentation and on pattern of metastatic spread and their correlation with the underlying biology of urothelial carcinoma. The wide range of treatments for advanced urothelial cancer, including combined chemotherapy regimens and immune checkpoint inhibitors, each result in treatment class-specific patterns of response and adverse events. Results of studies point to the need for a reliable biomarker, perhaps with imaging, that predicts prognosis and treatment response to systemic treatment, and can be used to select the most effective treatment while minimizing toxicity. This review of advanced urothelial cancer introduces the latest advances in genetic profiling, the current role of imaging, the radiographic appearance of treatment response and their toxicities, and details potential future areas of imaging research.

Association of Streptococcus bovis endocarditis and advanced colorectal neoplasia: a case-control study.

OBJECTIVE: To study the association between Streptococcus bovis (S. bovis) endocarditis and advanced colorectal neoplasia. METHODS: This was a case-control study of patients with S. bovis endocarditis undergoing colonoscopic evaluation. Patients were matched 1:20 with controls by gender and age (±2 years) from a large screening colonoscopy database. The baseline, colonoscopic and clinicopathological characteristics of patients with S. bovis endocarditis were analyzed. RESULTS: From 1996 to 2010, 18 adult patients with S. bovis bacteremia were identified, of whom 10 with infective endocarditis (IE) underwent colonoscopic evaluation. Endocarditis involved a native or prosthetic valve in six and four of those patients, respectively. All 10 patients recovered without recurrence of IE (mean follow-up duration 49.6 months). None had a concurrent or preceding history of colon disease and only one had subclinical chronic liver disease. Advanced neoplasia, defined as the presence of polyps ≥1 cm (n = 6), villous histology (n = 3), high-grade focal dysplasia (n = 1) or cancer (n = 1), was found under colonoscopy in 6 of the 10 cases (60.0%) compared with 13/200 (6.5%) matched controls (OR 21.6, 95% CI 5.4-86.1, P < 0.0001). CONCLUSIONS: S. bovis endocarditis is strongly associated with the presence of advanced colorectal neoplasia. In the absence of any contraindication, colonoscopic examination is strongly recommended in patients with endocarditis. The exact pathophysiological mechanisms underlying this association and the predilection for S. bovis bacteremia in patients with advanced colonic neoplasia remain unclear.

CYP2C19 genetic polymorphism, rabeprazole and esomeprazole have no effect on the antiplatelet action of clopidogrel.

The aim of this study is to investigate the effect of CYP2C19 polymorphism and cotherapy with rabeprazole or esomeprazole on the antiplatelet effect of clopidogrel. Patients receiving clopidogrel 75 mg ± rabeprazole or esomeprazole underwent genotyping for CYP2C19*2 and CYP2C19*3, and vasodilator-stimulated phosphoprotein testing to measure platelet reactivity index (PRI). Two hundred thirty-nine consecutive patients were enrolled as follows: 92 clopidogrel (C group), 94 clopidogrel + rabeprazole (CR), and 53 clopidogrel + esomeprazole (CE). Forty-five patients had loss of function (LOF) polymorphism (43 heterozygous; 2 homozygous mutant for CYP2C19*2). The mean PRI was 20.7% ± 21.9% in the C group, 19.1% ± 20.9% in the CR group, and 24.5% ± 22.9% in the CE group (P = NS). High on-treatment platelet reactivity (HPR), defined as PRI >50%, was observed in 12 (13.0%), 13 (13.8%), and 10 (18.9%) patients on C, CR, and CE, respectively (P = NS). HPR was similar in rapid metabolizers between groups. On multivariate logistic regression, neither CYP2C19 LOF alleles nor proton pump inhibitor cotherapy were associated with HPR. The use of proton pump inhibitors was indicated in 30.6% of recipients. As a conclusion, CYP2C19*2 LOF allele and the use of esomeprazole or rabeprazole have no effect on the action of clopidogrel.

Peripheral vascular tumors and vascular malformations: imaging (magnetic resonance imaging and conventional angiography), pathologic correlation and treatment options.

Vascular anomalies are classified into vascular tumors (infantile hemangioma) and vascular malformations. Vascular malformations are divided into slow flow and high flow subtypes. Magnetic resonance imaging helps in classification and assessing extent and distribution. Conventional angiography also known as digital subtraction angiography is pivotal in assessment of fine vascular details and treatment planning. Imaging correlates well with histopathology. We review recent development in imaging techniques of various vascular anomalies most of which are affecting the peripheral system which potentially may broaden understanding of their diagnosis, classification and treatment.

Proton pump inhibitors have no measurable effect on calcium and bone metabolism in healthy young males: a prospective matched controlled study.

OBJECTIVES: Proton pump inhibitors (PPIs) are associated with an increased risk of bone fractures. This study sought to evaluate the effect of PPIs on biochemical markers of calcium and bone metabolism. METHODS: Prospective matched controlled study involving healthy adult males (age 18-50years) suffering from frequent heartburn. Patients received standard-dose PPI for 12weeks and were matched by age with healthy controls. Blood studies were taken at 0, 1 and 3months for biochemical markers of mineral and bone metabolism. Two-way (time and PPI treatment) repeated measures analysis of variance (RM-ANOVA) and multiple linear regression were used for analysis. RESULTS: A total of 58 participants (29 per group) completed the study. Mean age of participants was 33.2±7.5years. Baseline characteristics and biomarkers were similar for both groups except for higher BMI (28.6 vs. 25.6kg/m(2), p=0.008) and serum C-terminal cross linked telopeptides of type I collagen [CrossLaps, (300 vs. 228pg/ml, p=0.028)] in the PPI group. There was no difference in parathormone (PTH), ionized calcium, vitamin D, osteocalcin and CrossLaps between the PPI and control subjects (all non-significant; 2-way RM-ANOVA). Multiple linear regression modeling showed no effect of PPIs on any of the studied calcium or bone metabolism biomarkers. CONCLUSION: PPI intake for 12weeks has no measurable effect on calcium or bone metabolism in healthy young males.

Alcohol consumption is a risk factor for colonic diverticulosis.

BACKGROUND AND AIM: The exact factors predisposing to colonic diverticulosis other than age are unknown. METHODS: Cross-sectional study of asymptomatic subjects undergoing screening colonoscopy. A detailed dietary and social questionnaire was completed on all participants. A worldwide review of the literature was performed to further investigate any association between identified risk factors and diverticulosis. RESULTS: Seven hundred forty-six consecutive individuals were enrolled (mean age, 61.1±8.3 y; female: male=0.98). Overall, the prevalence of diverticulosis was 32.8% (95% CI, 29.5-36.2). Diverticula were left-sided, right-sided, or both in 71.5%, 5.8%, and 22.7% of affected subjects, respectively. On univariate analysis, age, sex, adenomatous polyps, advanced neoplasia (adenoma≥1 cm, villous histology, or cancer), aspirin, and alcohol use were significantly associated with diverticulosis. Diet, body mass index, physical activity, and bowel habits were not associated with the disease. On multivariate analysis, increasing age (P<0.001), advanced neoplasia (P=0.021), and alcohol consumption (P<0.001) were significantly associated with diverticulosis. The adjusted odds ratio for diverticulosis in alcohol users was 1.91 (1.36 to 2.69), with increasing prevalence with higher alcohol consumption (P-value for trend=0.001). When the prevalence of diverticulosis reported from 18 countries was analyzed against alcohol use, there was a strong correlation with national per-capita alcohol consumption rates (Pearson correlation coefficient r=0.68; P=0.002). CONCLUSIONS: Alcohol use is a significant risk factor for colonic diverticulosis and may offer a partial explanation for the existing East-West paradox in disease prevalence and phenotype. Further studies are needed to investigate this association and its putative pathophysiological mechanisms.

Isolated hepatic artery injury in blunt abdominal trauma presenting as upper gastrointestinal bleeding: treatment with transcatheter embolisation.

Liver injury in blunt abdominal trauma is common. However, not often does blunt trauma cause injury to the anatomical structures of the porta hepatis. Isolated injury of the hepatic artery has been rarely reported in the literature. Such injury may be lethal and requires immediate diagnosis and management. This report describes an unusual case of blunt abdominal trauma resulting in hepatic and gastroduodenal artery dissection, with pseudoaneurysm formation complicated by active upper gastrointestinal bleeding. The injury was managed by transcatheter embolisation. Awareness of this diagnosis should facilitate management of similar trauma cases.

Popliteal artery entrapment presenting as acute limb ischemia: treatment with intra-arterial thrombolysis. Case report and review of the literature.

Popliteal artery entrapment syndrome (PAES) is a relatively rare condition, which occurs predominantly in active young adults who lack atherogenic risk factors. It has been rarely reported in patients under the age of 18 years. The most common presentation in the early stages is intermittent claudication; however, in the later stages of undiagnosed PAES, acute ischemia can occur as a result of complete arterial occlusion or embolism. We present a 14-year-old boy, who presented with acute limb ischemia which was managed with a multidisciplinary approach.

A randomized trial of standard-dose versus half-dose rabeprazole, clarithromycin, and amoxicillin in the treatment of Helicobacter pylori infection.

OBJECTIVES: To evaluate the efficacy and safety of a standard-dose versus half-dose 10-day triple regimen for the eradication of Helicobacter pylori infection. METHODS: A total of 115 consecutive patients with documented infection were enrolled in this open-label trial. Group A (standard dose) received rabeprazole (20 mg), amoxicillin (1 g), and clarithromycin (500 mg), all twice daily for 10 days. Group B (half dose) received rabeprazole (10 mg), amoxicillin (500 mg), and clarithromycin (250 mg), all twice daily for 10 days. (14)C urea breath tests were performed a minimum of 4 weeks after treatment and a minimum of 2 weeks off any acid-suppressive therapy. Compliance and adverse effects were evaluated throughout the treatment period. RESULTS: A total of 115 patients were enrolled (59 women and 56 men; mean age 47.1±14.0 years). Eradication occurred in 45 of 58 patients [77.6%; 95% confidence interval (CI): 66.9-88.3%] in the standard-dose group versus 44 of 57 in the half-dose group (77.2%; 95% CI: 66.3-88.1%) on an intent-to-treat (ITT) analysis (P=1.00). Per protocol eradication rates were 45 of 57 (78.9%; 95% CI: 68.4-85.9%) and 44 of 54 (81.5%; 95% CI: 71.1-91.8%), respectively (P=0.81). The number of patients reporting any adverse effect was significantly higher in the standard-dose group (64.9 vs. 40.4%; P=0.014). The cost of treatment was significantly less in patients receiving the half-dose regimen (ITT analysis; P<0.05). The number needed to harm to suffer one additional failure in the half-dose over the standard-dose arm was 250 (ITT analysis). CONCLUSION: A half-dose 10-day regimen of rabeprazole, amoxicillin, and clarithromycin is equally effective but cheaper and better tolerated than its standard-dose regimen in the treatment of Helicobacter pylori. Eradication rates of both regimens are, however, suboptimal compared with accepted standards.

Severe hepatotoxicity associated with the combination of spiramycin plus metronidazole.

Drug-induced liver injury (DILI) is a leading cause of acute liver failure and is the most frequent reason for post-marketing drug withdrawal. The spectrum of liver injury is wide, ranging from mild and subclinical injury, noticeable only on routine biochemical testing, to fulminant liver failure and death. Antibiotics, as a group, are a leading cause of DILI. We herein describe 4 patients who developed moderate to severe hepatotoxicity after exposure to a commercially - available combination of two antibiotics - spiramycin and metronidazole - commonly used for the treatment and prevention of periodontal infections. No other aetiology for liver injury could be identified in all cases. Two patients recovered spontaneously, and two had a more severe course, one responding to corticosteroids and mycophenolate mofetil and the other requiring liver transplantation for subacute massive necrosis.

Investigational agents for the irritable bowel syndrome.

IMPORTANCE OF THE FIELD: Irritable bowel syndrome (IBS) is a common disorder with significant health and economic consequences. The etiology of IBS is complex and appears to be multifactorial. Traditional IBS therapies have been directed primarily at the relief of individual symptoms but have been largely disappointing. This has triggered the search for newer treatment strategies with improved patient outcomes. AREAS COVERED IN THIS REVIEW: Enhanced knowledge about the putative pathophysiology of IBS has allowed the identification of new mechanistic targets for treatment. Our aim is to review emerging and promising drugs in the treatment of IBS based on disease pathophysiology. Data were extracted using Medline and PubMed search engines until January 2010. Abstracts were identified through 'Web of Science' and abstract supplements of major gastrointestinal scientific meetings. Drugs were classified according to mechanism of action and those with efficacy in trials involving human subjects examined. WHAT THE READER WILL GAIN: Additional insight into the pathophysiology as well as current and prospective treatments of IBS. TAKE HOME MESSAGE: A multitude of putative drug targets have been identified and some novel treatments have progressed through to human clinical trials, but very few will be approved for the market in the near future. Moreover, and in keeping with the complex and multifactorial nature of this syndrome, it is unlikely that there will be one dominant and universally effective form of therapy for all IBS patients.

Duration of pain is correlated with elevation in liver function tests in patients with symptomatic choledocholithiasis.

BACKGROUND & AIMS: We assessed the temporal relationship between abdominal pain and elevation in liver function tests (LFTs) in patients with acute symptomatic choledocholithiasis. METHODS: Retrospective study of patients that presented within 12 hours of pain onset and were subsequently found to have choledocholithiasis. RESULTS: We identified 40 patients with complete medical records. Levels of aspartate and alanine aminotransferases (AST and ALT) correlated with duration of pain (Pearson correlation, r = 0.633 and 0.622 respectively, P < .001 for both); the correlation was not as strong for γ-glutamyl transpeptidase (GGT) (r = 0.326, P = .046) and was not significant for alkaline phosphatase or bilirubin. This temporal association was stronger in patients that had undergone cholecystectomy versus those with intact gallbladders (for ALT, r = 0.603 vs r = 0.311, respectively). Eighteen patients, evaluated within 6 hours of pain, had normal or minimal alterations in LFTs; transabdominal ultrasound was abnormal in 6 (sensitivity 33.3%). All had repeat LFTs within 24 hours (mean 10.3 ± 6.9 hours later) and large increases in ALT and aspartate aminotransferase levels (mean 10.5- and 6.8-fold respectively; P < .01 for both), intermediate increases in glutamyl transpeptidase levels, (mean 4-fold, P < .05), and no changes in alkaline phosphatase levels. This significant increase in LFTs was the only indication of biliary pathology before endoscopy in 11/18 patients. CONCLUSIONS: Increasing duration of pain is associated with increasing LFTs (particularly transaminases) in patients with acute symptomatic choledocholithiasis. Patients with normal LFTs and ultrasound upon presentation should have repeat LFTs if biliary pain is suspected. The absence of significant biochemical abnormalities within the first 24 hours makes the diagnosis of symptomatic choledocholithiasis unlikely.