Irina Rinta-Kiikka

A prospective diagnostic accuracy study of 18F-fluorodeoxyglucose positron emission tomography/computed tomography, multidetector row computed tomography, and magnetic resonance imaging in primary diagnosis and staging of pancreatic cancer.

Objective:To prospectively compare the accuracy of combined positron emission tomography/computed tomography using 18F-fluorodeoxyglucose (FDG-PET/CT), multidetector row computed tomography (MDCT), and magnetic resonance imaging (MRI) in the evaluation of patients with suspected pancreatic malignancy. Summary Background Data:FDG-PET/CT imaging is increasingly used for staging of pancreatic cancer. Preliminary data suggest a significant influence of FDG-PET/CT on treatment planning, although its role is still evolving. Methods:Thirty-eight consecutive patients with suspicion of pancreatic malignancy were enrolled. Patients underwent a protocol including FDG-PET/CT, MDCT, and MRI combined with magnetic resonance cholangiopancreatography, all of which were blindly evaluated. The findings were confirmed macroscopically at operation and/or by histopathologic analysis (n = 29) or follow-up (n = 9). Results of TNM classification of different imaging methods were compared with clinical TNM classification. Results:Pancreatic adenocarcinoma was diagnosed in 17 patients, neuroendocrine tumor in 3, mass-forming pancreatitis in 4, cystic lesion in 6, and fibrosis in 2. Six patients had a finding of a normal pancreas. The diagnostic accuracy of FDG-PET/CT for pancreatic malignancy was 89%, compared with 76% and 79% for MDCT and MRI, respectively. In the differential diagnosis of suspected malignant biliary stricture at endoscopic retrograde cholangiopancreaticography (n = 21), FDG-PET/CT had a positive predictive value of 92%. In 17 patients with advanced pancreatic adenocarcinoma, FDG-PET/CT had a sensitivity of 30% for N- and 88% for M-staging. Both MDCT and MRI had sensitivities of 30% for N- and 38% for M-staging. Furthermore, the clinical management of 10 patients (26%) was altered after FDG-PET/CT. Conclusion:FDG-PET/CT was more sensitive than conventional imaging in the diagnosis of both primary pancreatic adenocarcinoma and associated distant metastases. In contrast, the sensitivity of FDG-PET/CT was poor in detecting local lymph node metastasis, which would have been important for an assessment of resectability. We recommend the use of FDG-PET/CT in the evaluation of diagnostically challenging cases, especially in patients with biliary strictures without evidence of malignancy in conventional imaging.

Antibiotic Therapy vs Appendectomy for Treatment of Uncomplicated Acute Appendicitis: The APPAC Randomized Clinical Trial

IMPORTANCE An increasing amount of evidence supports the use of antibiotics instead of surgery for treating patients with uncomplicated acute appendicitis. OBJECTIVE To compare antibiotic therapy with appendectomy in the treatment of uncomplicated acute appendicitis confirmed by computed tomography (CT). DESIGN, SETTING, AND PARTICIPANTS The Appendicitis Acuta (APPAC) multicenter, open-label, noninferiority randomized clinical trial was conducted from November 2009 until June 2012 in Finland. The trial enrolled 530 patients aged 18 to 60 years with uncomplicated acute appendicitis confirmed by a CT scan. Patients were randomly assigned to early appendectomy or antibiotic treatment with a 1-year follow-up period. INTERVENTIONS Patients randomized to antibiotic therapy received intravenous ertapenem (1 g/d) for 3 days followed by 7 days of oral levofloxacin (500 mg once daily) and metronidazole (500 mg 3 times per day). Patients randomized to the surgical treatment group were assigned to undergo standard open appendectomy. MAIN OUTCOMES AND MEASURES The primary end point for the surgical intervention was the successful completion of an appendectomy. The primary end point for antibiotic-treated patients was discharge from the hospital without the need for surgery and no recurrent appendicitis during a 1-year follow-up period. RESULTS There were 273 patients in the surgical group and 257 in the antibiotic group. Of 273 patients in the surgical group, all but 1 underwent successful appendectomy, resulting in a success rate of 99.6% (95% CI, 98.0% to 100.0%). In the antibiotic group, 70 patients (27.3%; 95% CI, 22.0% to 33.2%) underwent appendectomy within 1 year of initial presentation for appendicitis. Of the 256 patients available for follow-up in the antibiotic group, 186 (72.7%; 95% CI, 66.8% to 78.0%) did not require surgery. The intention-to-treat analysis yielded a difference in treatment efficacy between groups of -27.0% (95% CI, -31.6% to ∞) (P = .89). Given the prespecified noninferiority margin of 24%, we were unable to demonstrate noninferiority of antibiotic treatment relative to surgery. Of the 70 patients randomized to antibiotic treatment who subsequently underwent appendectomy, 58 (82.9%; 95% CI, 72.0% to 90.8%) had uncomplicated appendicitis, 7 (10.0%; 95% CI, 4.1% to 19.5%) had complicated acute appendicitis, and 5 (7.1%; 95% CI, 2.4% to 15.9%) did not have appendicitis but received appendectomy for suspected recurrence. There were no intra-abdominal abscesses or other major complications associated with delayed appendectomy in patients randomized to antibiotic treatment. CONCLUSIONS AND RELEVANCE Among patients with CT-proven, uncomplicated appendicitis, antibiotic treatment did not meet the prespecified criterion for noninferiority compared with appendectomy. Most patients randomized to antibiotic treatment for uncomplicated appendicitis did not require appendectomy during the 1-year follow-up period, and those who required appendectomy did not experience significant complications. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01022567.

Adolescence risk factors are predictive of coronary artery calcification at middle age: the Cardiovascular Risk in Young Finns Study

OBJECTIVES The purpose of this study was to examine the roles of adolescence risk factors in predicting coronary artery calcium (CAC). BACKGROUND Elevated coronary heart disease risk factor levels in adolescence may predict subsequent CAC independently of change in risk factor levels from adolescence to adulthood. METHODS CAC was assessed in 589 subjects 40 to 46 years of age from the Cardiovascular Risk in Young Finns Study. Risk factor levels were measured in 1980 (12 to 18 years) and in 2007. RESULTS The prevalence of any CAC was 19.2% (27.9% in men and 12.2% in women). Age, levels of systolic blood pressure (BP), total cholesterol, and low-density lipoprotein cholesterol (LDL-C) in adolescence, as well as systolic BP, total cholesterol, diastolic BP, and pack-years of smoking in adulthood were higher among subjects with CAC than those without CAC. Adolescence LDL-C and systolic BP levels predicted CAC in adulthood independently of 27-year changes in these risk factors. The multivariable odds ratios were 1.34 (95% confidence interval: 1.05 to 1.70; p=0.02) and 1.38 (95% confidence interval: 1.08 to 1.77; p=0.01), for 1-SD increase in adolescence LDL-C and systolic BP, respectively. Exposure to both of these risk factors in adolescence (defined as values at or above the age- and sex-specific 75th percentile) substantially increased the risk of CAC (multivariable odds ratio: 3.5 [95% confidence interval: 1.7 to 7.2; p=0.007]) between groups with no versus both risk factors. CONCLUSIONS Elevated adolescence LDL-C and systolic BP levels are independent predictors of adulthood CAC, indicating that adolescence risk factor levels play an important role in the pathogenesis of coronary heart disease.

Cardiac Magnetic Resonance Imaging in the Evaluation of the Late Effects of Anthracyclines Among Long-Term Survivors of Childhood Cancer

OBJECTIVES This study sought to examine the left ventricular (LV) and right ventricular (RV) function and signs of focal fibrosis among long-term survivors of childhood cancer with the use of cardiac magnetic resonance (CMR) imaging. BACKGROUND Increased myocardial fibrosis has been detected in the endomyocardial biopsies of survivors. CMR has established its role in the assessment of both cardiac function and structure, and focal fibrosis of the myocardium is detectable with late gadolinium enhancement (LGE). METHODS Sixty-two anthracycline-exposed long-term survivors of childhood cancer were studied at a mean age of 14.6 years. The LV and RV ejection fractions (EFs) and volumes were measured, and LGE was assessed using CMR. RESULTS An abnormal LV function (EF <45%) was detected in 18% (11 of 62) of the survivors, and an abnormal RV function was detected in 27% (17 of 62) of the survivors. Subnormal (45% ≤ EF <55%) LV function were demonstrated in 61% (38 of 62) and subnormal RV function in 53% (33 of 62) of the survivors, respectively. Both the LV and RV end-systolic and LV end-diastolic volumes were increased compared with reference values. None of the study patients showed LGE. CONCLUSIONS A considerable proportion of the long-term survivors of childhood cancer with anthracycline exposure demonstrate signs of cardiac dysfunction detectable by CMR, with the RV also being involved. Yet, myocardial fibrosis does not seem to be detectable at a median of 7.8 years after anthracycline therapy.

Accuracy of 18F-FDG PET/CT, Multidetector CT, and MR Imaging in the Diagnosis of Pancreatic Cysts: A Prospective Single-Center Study

Accurate diagnosis of the nature of pancreatic cysts is challenging but more important than ever, in part because of the increasing number of incidental cystic findings in the pancreas. Preliminary data suggest that 18F-FDG PET/CT may have a significant influence on clinical decision making, although its role is still evolving. Our aim was to prospectively compare the accuracy of combined 18F-FDG PET and contrast-enhanced CT (18F-FDG PET/CT), multidetector CT (MDCT), and MR imaging in differentiating malignant from benign pancreatic cysts. Methods: Thirty-one consecutive patients with pancreatic cysts were enrolled in the study. They underwent a protocol including 18F-FDG PET/CT, MDCT, and MR imaging combined with MR cholangiopancreatography, all of which were evaluated in a masked manner. The findings were confirmed macroscopically at surgery or histopathologic analysis (n = 22) or at follow-up (n = 9). Results: Of the 31 patients, 6 had malignant and 25 had benign lesions. The diagnostic accuracy was 94% for 18F-FDG PET/CT, compared with 77% and 87% for MDCT (P < 0.05) and MR imaging, respectively. 18F-FDG PET/CT had a negative predictive value of 100% and a positive predictive value of 75% for pancreatic cysts. The maximum standardized uptake value was significantly higher in malignant (7.4 ± 2.6) than in benign lesions (2.4 ± 0.8) (P < 0.05). When the maximum standardized uptake value was set at 3.6, the sensitivity and specificity were 100% and 88%, respectively. Furthermore, when compared with MDCT and MR imaging, respectively, 18F-FDG PET/CT altered the clinical management of 5 and 3 patients, respectively. Conclusion: 18F-FDG PET/CT is an accurate imaging modality for differentiating between benign and malignant pancreatic cysts. We recommend the use of 18F-FDG PET/CT in the evaluation of diagnostically challenging pancreatic cysts.

Spyglass single-operator peroral cholangioscopy seems promising in the evaluation of primary sclerosing cholangitis-related biliary strictures

Abstract Early diagnosis of dysplastic changes and exclusion of cholangiocarcinoma (CCA) in patients with primary sclerosing cholangitis (PSC) remain a major clinical challenge. Although SpyGlass single-operator cholangioscopy (SOC) appears effective in diagnostics of indeterminate biliary strictures, there are only few studies on its safety in PSC-related strictures. Objective. The aim of this study was to assess the clinical feasibility of SOC and directed biopsies, flow cytometry, and brush cytology in PSC patients. Materials and methods. Eleven consecutive patients (median age 45 years, 5 females) undergoing SOC for progression of PSC in a single tertiary center were included in a prospective observational study. Results. Brush sample and directed biopsies were successfully acquired from strictures in all cases. Samples were adequate for cytological and histological diagnosis in 9 (82%) and 10 patients (91%), respectively. There were two cases of pancreatitis. In one patient, flow cytometry showed aneuploidy, which resulted in closer follow-up. Conclusions. SpyGlass SOC and directed biopsies seem to offer a feasible and promising method in evaluation of PSC-related strictures. However, the long-term prognostic value it adds to cytology and flow cytometry remains to be assessed in future trials.

Childhood Psychosocial Factors and Coronary Artery Calcification in Adulthood: The Cardiovascular Risk in Young Finns Study.

IMPORTANCE There is increasing evidence supporting the importance of psychosocial factors in the pathophysiology of atherosclerotic disease. They have been shown to be associated with the population attributable risk for myocardial infarction. OBJECTIVE To determine if a score of favorable childhood psychosocial factors would be associated with decreased coronary artery calcification in adulthood. DESIGN, SETTING, AND PARTICIPANTS The analyses were performed in 2015 using data gathered in 1980 and 2008 within the longitudinal Cardiovascular Risk in Young Finns Study. The data source consisted of 311 individuals who had psychosocial factors measured at ages 12 years to 18 years and coronary artery calcification measured 28 years later in adulthood. The summary measure of psychosocial factors in childhood comprised measures of socioeconomic factors, emotional factors, parental health behaviors, stressful events, self-regulation of the child, and social adjustment of the child. MAIN OUTCOMES AND MEASURES Coronary artery calcification at ages 40 years to 46 years. RESULTS Of the 311 participants, 48.2% were men. Of the participants, 55 (17.7%) had some calcium observed in their coronary arteries. A 1-SD increase in a favorable summary score of childhood psychological factors was associated with an adulthood coronary artery calcification probability of 0.85 (95% CI, 0.76-0.95) (P = .006). This inverse relationship remained significant after adjustment for age, sex, and conventional childhood risk factors (0.85; 95% CI, 0.74-0.97; P = .02) or for age, sex, adulthood conventional cardiovascular risk factors, socioeconomic status, social support, and depressive symptoms (0.83; 95% CI, 0.71-0.97; P = .02). CONCLUSIONS AND RELEVANCE In this longitudinal study, we observed an independent association between childhood psychosocial well-being and reduced coronary artery calcification in adulthood. A positive childhood psychosocial environment may decrease cardiovascular risk in adulthood and may represent a potentially modifiable risk determinant.

Coronary heart disease risk factors, coronary artery calcification and epicardial fat volume in the Young Finns Study.

AIMS We investigated associations of pre-clinical coronary heart disease (CHD), adolescence and adulthood CHD risk factors, and epicardial fat volume (EFV), which is thought to influence CHD pathology. METHODS AND RESULTS EFV and coronary calcium scores were quantified using computed tomography imaging for 557 subjects from the Cardiovascular Risk in Young Finns Study in 2007. CHD risk marker levels were assessed repeatedly from 1980 to 2007. Carotid intima-media thickness (cIMT), carotid distensibility, and brachial flow-mediated dilatation were measured by vascular ultrasound in 2007. Increased EFV was cross-sectionally associated with male sex, increased waist circumference, body-mass index (BMI), cIMT, metabolic syndrome prevalence, levels of apolipoprotein B, total cholesterol, low-density lipoprotein cholesterol, triglycerides, C-reactive protein, blood pressure, insulin, and fasting glucose, as well as ever smoking, alcoholic intake, and lower high-density lipoprotein cholesterol (HDL-C), carotid distensibility and physical activity in adulthood. In BMI-adjusted analyses, only apolipoprotein B, ever smoking, alcohol intake and metabolic syndrome prevalence were independently associated with EFV. In adolescence, skinfold thickness, BMI, and insulin levels were higher and HDL-C lower with increasing EFV. Subjects in the lowest vs. highest quarter of EFV had consistently lower BMI across the early life-course. CONCLUSION Associations of CHD risk markers with EFV were attenuated after multivariable adjustment. We found no evidence of increased EFV being independently associated with pre-clinical atherosclerosis. EFV was most strongly associated with BMI and waist circumference. Subjects with higher EFV had consistently higher BMI from age 12 suggesting that life-long exposure to higher BMI influences the development of EFV.

Diagnostic workup of liver lesions: Too long time with too many examinations

Abstract Objective. Liver mass lesions are often detected incidentally. Subsequent imaging examinations and surveillance are not only expensive, but may also cause unnecessary concern to patients. The aim of this study was to evaluate retrospectively the possible delay in acquiring the diagnosis of liver mass lesions, and to estimate the number of imaging examinations performed during the diagnostic workup. Patients and methods. The study comprised 200 patients with liver mass lesion of unknown etiology. The time needed from referral to final diagnosis was assessed. All imaging examinations and biopsy findings (if available) during the diagnostic workup were recorded. Results. Out of the 200 lesions, 133 were malignant, 65 with hepatocellular cancer and 26 with cholangiocarcinoma. All except one were diagnosed within 8 weeks. Of the 67 benign lesions, there were 20 focal nodular hyperplasias and 20 hemangiomas. For the benign lesions, in 37% the diagnostic workup took >8 weeks. Repeated examinations were more common in benign lesions; but often redundant in both benign and malignant conditions in retrospect analysis. Conclusions. To confirm the diagnosis, benign lesions required more follow-up time and more repeated imaging examinations than malignant ones. A long surveillance for liver mass lesions in fear of malignancy seems not to be necessary, since virtually all malignant lesions were diagnosed within 8 weeks. Evaluating all lesions in a multidisciplinary team right from the beginning is advocated by a prospective study design.

Endoscopic biodegradable biliary stents in the treatment of benign biliary strictures: First report of clinical use in patients

The first clinical experience of endoscopically inserted polydioxanone biodegradable biliary stents (BDBS) in the treatment of benign biliary strictures is reported. Two patients with a benign common bile duct stricture were endoscopically treated with 8‐mm‐bore BDBS during endoscopic retrograde cholangiography. Both BDBS insertions were technically successful and without adverse events. At 6 months, the stricture resolution was excellent and BDBS degradation was predicted in repeated magnetic resonance imaging. The first experience with endoscopic BDBS seems promising in the treatment of benign biliary strictures. During 6 months of follow up, BDBS seemed sufficient for remodeling and resolution of strictures. Further studies are needed to confirm the effectiveness of biodegradable biliary stents in endoscopic management of benign biliary strictures.