Imaging of Tumor Hypoxia With 18F-EF5 PET/MRI in Cervical Cancer.

PURPOSE OF THE REPORT: The aim of this study was to evaluate the distribution of hypoxia using 18F-EF5 as a hypoxia tracer in cervical cancer patients with PET/MRI. We investigated the association between this 18F-EF5-PET tracer and the immunohistochemical expression of endogenous hypoxia markers: HIF1α, CAIX, and GLUT1. PATIENTS AND METHODS: Nine patients with biopsy-proven primary squamous cell cervix carcinoma (FIGO 2018 radiological stages IB1-IIIC2r) were imaged with dual tracers 18F-EF5 and 18F-FDG using PET/MRI (Int J Gynaecol Obstet. 2019;145:129-135). 18F-EF5 images were analyzed by calculating the tumor-to-muscle ratio to determine the hypoxic tissue (T/M ratio >1.5) and further hypoxic subvolume (HSV) and percentage hypoxic area. These 18F-EF5 hypoxic parameters were correlated with the size and localization of tumors in 18F-FDG PET/MRI and the results of hypoxia immunohistochemistry. RESULTS: All primary tumors were clearly 18F-FDG and 18F-EF5 PET positive and heterogeneously hypoxic with multiple 18F-EF5-avid areas in locally advanced cancer and single areas in clinically stage I tumors. The location of hypoxia was detected mainly in the periphery of tumor. Hypoxia parameters 18F-EF5 max T/M ratio and HSV in primary tumors correlated independently with the advanced stage (P = 0.036 and P = 0.040, respectively), and HSV correlated with the tumor size (P = 0.027). The location of hypoxia in 18F-EF5 imaging was confirmed with a higher hypoxic marker expression HIF1α and CAIX in tumor fresh biopsies. CONCLUSIONS: The 18F-EF5 imaging has promising potential in detecting areas of tumor hypoxia in cervical cancer.

Diagnostic efficiency of whole-body 18F-FDG PET/MRI, MRI alone, and SUV and ADC values in staging of primary uterine cervical cancer.

BACKGROUND: The use of PET/MRI for gynecological cancers is emerging. The purpose of this study was to assess the additional diagnostic value of PET over MRI alone in local and whole-body staging of cervical cancer, and to evaluate the benefit of standardized uptake value (SUV) and apparent diffusion coefficient (ADC) in staging. METHODS: Patients with histopathologically-proven cervical cancer and whole-body 18F-FDG PET/MRI obtained before definitive treatment were retrospectively registered. Local tumor spread, nodal involvement, and distant metastases were evaluated using PET/MRI or MRI dataset alone. Histopathology or clinical consensus with follow-up imaging were used as reference standard. Tumor SUVmax and ADC were measured and SUVmax/ADC ratio calculated. Area under the curve (AUC) was determined to predict diagnostic performance and Mann-Whitney U test was applied for group comparisons. RESULTS: In total, 33 patients who underwent surgery (n = 23) or first-line chemoradiation (n = 10) were included. PET/MRI resulted in higher AUC compared with MRI alone in detecting parametrial (0.89 versus 0.73), vaginal (0.85 versus 0.74), and deep cervical stromal invasion (0.96 versus 0.74), respectively. PET/MRI had higher diagnostic confidence than MRI in identifying patients with radical cone biopsy and no residual at hysterectomy (sensitivity 89% versus 44%). PET/MRI and MRI showed equal AUC for pelvic nodal staging (both 0.73), whereas AUC for distant metastases was higher using PET/MRI (0.80 versus 0.67). Tumor SUVmax/ADC ratio, but not SUVmax or ADC alone, was significantly higher in the presence of metastatic pelvic lymph nodes (P < 0.05). CONCLUSIONS: PET/MRI shows higher accuracy than MRI alone for determining local tumor spread and distant metastasis emphasizing the added value of PET over MRI alone in staging of cervical cancer. Tumor SUVmax/ADC ratio may predict pelvic nodal involvement.

The value of combined positron emission tomography/magnetic resonance imaging to diagnose inflammatory bowel disease: a prospective study.

BACKGROUND: The clinical utility of positron emission tomography/magnetic resonance imaging (PET/MRI) in comparison to standard work-up with patients with known or suspected inflammatory bowel disease (IBD) is unknown. PURPOSE: To evaluate the value of 18F-fluorodeoxyglucose (18F-FDG) PET/MRI in the diagnostics of IBD and further compare the data obtained using PET/MRI to histological findings. MATERIALS AND METHODS: Ten patients with relapse in IBD or with symptoms of suspected IBD were recruited either from a gastroenterology outpatient clinic or from a hospital ward. Intestinal inflammation was assessed with histology and 18F-FDG PET/MRI. Maximum standard uptake values (SUVmax) were calculated in six regions of the intestine (small bowel, ascending, transverse, descending and sigmoid colon, and rectum) and compared to histological analysis of inflammation activity. RESULTS: The study showed that both the inflammation activity (P = 0.008) and the region of the biopsy in the intestine (P = 0.015) had a significant effect on SUV. SUVs obtained from severe inflammation activity emerged significantly from the background (P = 0.006). In addition, the SUVs obtained from moderate inflammation raised from background, but the difference was not statistically significant (P = 0.083), while SUVs of mild inflammation were at the same level with SUVs of normal bowel wall (P = 0.988). CONCLUSION: 18F-FDG PET/MRI is a promising method of detecting especially severe inflammatory bowel lesions. More data are required to define its sensitivity and specificity.

A Mayer-Rokitansky-Kuster-Hauser patient with leiomyoma and dysplasia of neovagina: a case report.

BACKGROUND: Most patients with congenital uterus and vaginal aplasia (i.e., Mayer-Rokitansky-Kuster-Hauser [MRKH] syndrome) have rudimentary pelvic uterine structures that contain smooth muscle. Although leiomyomas and dysplasia of vaginal mucosa are relatively common in the general population, they are rare in MRKH patients. Data on the vulnerability of neovaginas to HPV-associated dysplasia are limited. CASE PRESENTATION: A rare case of an MRKH patient with two gynaecological conditions detected during long-term gynaecological follow-up is presented. At the age of 21, the patient was treated for HPV-associated neovaginal dysplasia. At the age of 47, a pelvic leiomyoma was detected with transvaginal ultrasound and confirmed with magnetic resonance imaging. CONCLUSION: A Pap smear or human papillomavirus testing is indicated in sexually active MRKH women. Uterine rudiments contain smooth muscle, which facilitates the development of oestrogen-dependent diseases, such as leiomyomas and adenomyosis. Although magnetic resonance imaging is recommended in cases of a pelvic mass, easily attainable and cost-efficient transvaginal ultrasound offers high diagnostic accuracy in patients with a surgically created neovagina and is suitable for the patients' follow-up. Guidelines for the gynaecological follow-up of MRKH patients are warranted.

The Accuracy of Low-dose Computed Tomography Protocol in Patients With Suspected Acute Appendicitis: The OPTICAP Study.

OBJECTIVE: To compare diagnostic accuracy of contrast enhanced low-dose computed tomography (CT) accomplished in the OPTICAP trial phantom phase to standard CT in patients with suspected acute appendicitis. BACKGROUND: Increasing use of CT as the gold standard in diagnosing acute appendicitis has raised concerns regarding radiation exposure. Unenhanced low-dose CT protocols have shown similar diagnostic accuracy with standard CT for diagnosing appendicitis. To our knowledge, there are no other trials in which the same patient with suspected acute appendicitis underwent both standard and low-dose CT allowing interpatient comparison. METHODS: OPTICAP is an interpatient protocol sequence randomized noninferiority single-center trial performed at Turku University Hospital between November, 2015 and August, 2016. Sixty patients with suspected acute appendicitis and body mass index <30 kg/m were enrolled to undergo both standard and low-dose contrast enhanced CT scans, which were categorized as normal, uncomplicated or complicated appendicitis by 2 radiologists in blinded manner. All patients with CT confirmed appendicitis underwent appendectomy to obtain histopathology. RESULTS: The low-dose protocol was not inferior to standard protocol in terms of diagnostic accuracy; 79% [95% confidence interval (CI) 66%-89%) accurate diagnosis in low-dose and 80% (95% CI 67%-90%) in standard CT by primary radiologist. Accuracy to categorize appendicitis severity was 79% for both protocols. The mean radiation dose of low-dose CT was significantly lower compared with standard CT (3.33 and 4.44 mSv, respectively). CONCLUSION: Diagnostic accuracy of contrast enhanced low-dose CT was not inferior to standard CT in diagnosing acute appendicitis or distinguishing between uncomplicated and complicated acute appendicitis in patients with a high likelihood of acute appendicitis. Low-dose CT enabled significant radiation dose reduction.

PET/CT for Evaluation of Ovarian Cancer.

Ovarian cancer is the leading cause of death from gynecologic cancer in the developed countries. It is usually diagnosed in advanced stage since it is often symptomless or symptoms are nonspecific in early course of the disease. It has a high recurrence rate and poor prognosis in advanced disease. Ovarian cancer has distinct type of disease spread in abdomen and above diaphragm. Surgery is irreplaceable in staging but multimodality imaging approach is often needed during the diagnosis, treatment monitoring, and follow-up of patients with ovarian cancer, typically ultrasound, CT, MRI and PET/CT are the main modalities used. The current clinical role of PET/CT in evaluation of ovarian cancer during staging, treatment prognostication and response assessment, and in disease recurrence is discussed in this review compared to conventional imaging.

A randomised placebo-controlled double-blind multicentre trial comparing antibiotic therapy with placebo in the treatment of uncomplicated acute appendicitis: APPAC III trial study protocol.

INTRODUCTION: Recent studies show that antibiotic therapy is safe and feasible for CT-confirmed uncomplicated acute appendicitis. Spontaneous resolution of acute appendicitis has already been observed over a hundred years ago. In CT-confirmed uncomplicated acute diverticulitis (left-sided appendicitis), studies have shown no benefit from antibiotics compared with symptomatic treatment, but this shift from antibiotics to symptomatic treatment has not yet been widely implemented in clinical practice. Recently, symptomatic treatment of uncomplicated acute appendicitis has been demonstrated in a Korean open-label study. However, a double-blinded placebo-controlled study to illustrate the role of antibiotics and spontaneous resolution of uncomplicated acute appendicitis is still lacking. METHODS AND ANALYSIS: The APPAC III (APPendicitis ACuta III) trial is a multicentre, double-blind, placebo-controlled, superiority randomised study comparing antibiotic therapy with placebo in the treatment CT scan-confirmed uncomplicated acute appendicitis aiming to evaluate the role of antibiotics in the resolution of uncomplicated acute appendicitis. Adult patients (18-60 years) with CT scan-confirmed uncomplicated acute appendicitis (the absence of appendicolith, abscess, perforation and tumour) will be enrolled in five Finnish university hospitals.Primary endpoint is success of the randomised treatment, defined as resolution of acute appendicitis resulting in discharge from the hospital without surgical intervention within 10 days after initiating randomised treatment (treatment efficacy). Secondary endpoints include postintervention complications, recurrent symptoms after treatment up to 1 year, late recurrence of acute appendicitis after 1 year, duration of hospital stay, sick leave, treatment costs and quality of life. A decrease of 15 percentage points in success rate is considered clinically important difference. The superiority of antibiotic treatment compared with placebo will be analysed using Fisher's one-sided test and CI will be calculated for proportion difference. ETHICS AND DISSEMINATION: This protocol has been approved by the Ethics Committee of Turku University Hospital and the Finnish Medicines Agency (FIMEA). The findings will be disseminated in peer-reviewed academic journals. TRIAL REGISTRATION NUMBER: NCT03234296; Pre-results.

Five-Year Follow-up of Antibiotic Therapy for Uncomplicated Acute Appendicitis in the APPAC Randomized Clinical Trial.

Importance: Short-term results support antibiotics as an alternative to surgery for treating uncomplicated acute appendicitis, but long-term outcomes are not known. Objective: To determine the late recurrence rate of appendicitis after antibiotic therapy for the treatment of uncomplicated acute appendicitis. Design, Setting, and Participants: Five-year observational follow-up of patients in the Appendicitis Acuta (APPAC) multicenter randomized clinical trial comparing appendectomy with antibiotic therapy, in which 530 patients aged 18 to 60 years with computed tomography-confirmed uncomplicated acute appendicitis were randomized to undergo an appendectomy (n = 273) or receive antibiotic therapy (n = 257). The initial trial was conducted from November 2009 to June 2012 in Finland; last follow-up was September 6, 2017. This current analysis focused on assessing the 5-year outcomes for the group of patients treated with antibiotics alone. Interventions: Open appendectomy vs antibiotic therapy with intravenous ertapenem for 3 days followed by 7 days of oral levofloxacin and metronidazole. Main Outcomes and Measures: In this analysis, prespecified secondary end points reported at 5-year follow-up included late (after 1 year) appendicitis recurrence after antibiotic treatment, complications, length of hospital stay, and sick leave. Results: Of the 530 patients (201 women; 329 men) enrolled in the trial, 273 patients (median age, 35 years [IQR, 27-46]) were randomized to undergo appendectomy, and 257 (median age, 33 years, [IQR, 26-47]) were randomized to receive antibiotic therapy. In addition to 70 patients who initially received antibiotics but underwent appendectomy within the first year (27.3% [95% CI, 22.0%-33.2%]; 70/256), 30 additional antibiotic-treated patients (16.1% [95% CI, 11.2%-22.2%]; 30/186) underwent appendectomy between 1 and 5 years. The cumulative incidence of appendicitis recurrence was 34.0% (95% CI, 28.2%-40.1%; 87/256) at 2 years, 35.2% (95% CI, 29.3%-41.4%; 90/256) at 3 years, 37.1% (95% CI, 31.2%-43.3%; 95/256) at 4 years, and 39.1% (95% CI, 33.1%-45.3%; 100/256) at 5 years. Of the 85 patients in the antibiotic group who subsequently underwent appendectomy for recurrent appendicitis, 76 had uncomplicated appendicitis, 2 had complicated appendicitis, and 7 did not have appendicitis. At 5 years, the overall complication rate (surgical site infections, incisional hernias, abdominal pain, and obstructive symptoms) was 24.4% (95% CI, 19.2%-30.3%) (n = 60/246) in the appendectomy group and 6.5% (95% CI, 3.8%-10.4%) (n = 16/246) in antibiotic group (P < .001), which calculates to 17.9 percentage points (95% CI, 11.7-24.1) higher after surgery. There was no difference between groups for length of hospital stay, but there was a significant difference in sick leave (11 days more for the appendectomy group). Conclusions and Relevance: Among patients who were initially treated with antibiotics for uncomplicated acute appendicitis, the likelihood of late recurrence within 5 years was 39.1%. This long-term follow-up supports the feasibility of antibiotic treatment alone as an alternative to surgery for uncomplicated acute appendicitis. Trial Registration: ClinicalTrials.gov Identifier: NCT01022567.

11C-acetate PET/MRI in bladder cancer staging and treatment response evaluation to neoadjuvant chemotherapy: a prospective multicenter study (ACEBIB trial).

BACKGROUND: To evaluate the accuracy of 11C-acetate Positron Emission Tomography/Magnetic Resonance Imaging (PET/MRI) in bladder cancer (BC) staging and monitoring response to neoadjuvant chemotherapy (NAC). METHODS: Eighteen patients were prospectively enrolled. Fifteen treatment naive patients underwent 11C-acetate PET/MRI before transurethral resection of bladder tumor (TUR-BT) for primary tumor evaluation. Five patients with muscle invasive BC were imaged after NAC and prior to radical cystectomy (RC) with extended pelvic lymph node dissection (ePLND) for NAC treatment response evaluation. Two patients were part of both cohorts. 11C-acetate PET/MRI findings were correlated with histopathology. Accuracy for lymph node detection was evaluated on patient and the ePLND template (10 regions) levels. RESULTS: The sensitivity, specificity and accuracy of 11C-acetate PET/MRI for the detection of muscle invasive BC was 1.00, 0.69 and 0.73 while the area under the receiver operating characteristic curve (95% confidence interval) was 0.85 (0.55-1.0), respectively. All five NAC patients underwent chemotherapy as planned and 11C-acetate PET/MRI correctly staged three patients, overstaged one and understaged one patient compared with RC and ePLND findings. A total of 175 lymph node were removed, median of 35 (range, 27-43) per patient in five patients who had RC and ePLND while 12 (7%) harboured metastases. Sensitivity, specificity, accuracy and AUC for N-staging were 0.20, 0.96, 0.80 and 0.58 on the ePLND template (10 regions) level. CONCLUSIONS: 11C-acetate PET/MRI is feasible for staging of BC although sensitivity for the detection of nodal metastases is low. Monitoring response to NAC shows promise and warrants evaluation in larger studies. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01918592 , registered August 8 2013.

18F-FDG-PET/CT based total metabolic tumor volume change during neoadjuvant chemotherapy predicts outcome in advanced epithelial ovarian cancer.

OBJECTIVE: To evaluate the predictive potential of total metabolic tumor volume (MTV) reduction during neoadjuvant chemotherapy (NACT) with 18F-FDG-PET/CT in an advanced FIGO stage III/IV epithelial ovarian cancer (EOC) patient cohort. METHODS: Twenty-nine primarily inoperable EOC patients underwent 18F-FDG-PET/CT before and after NACT. The pre- and post-NACT total MTV, in addition to the percentage MTV reduction during NACT, were compared with primary therapy outcome and progression-free survival (PFS). ROC-analysis determined an optimal threshold for MTV reduction identifying patients with progressive or stable disease (PD/SD) at the end of primary therapy. A multivariate analysis with residual tumor (0/>0), FIGO stage (III/IV) and MTV reduction compared to PFS was performed. The association between MTV reduction and overall survival (OS) was evaluated. RESULTS: The median pre- and post-NACT total MTV were 352 cm3 (range 150 to 1322 cm3) and 51 cm3 (range 0 to 417 cm3), respectively. The median MTV reduction during NACT was 89% (range 24% to 100%). Post-NACT MTV and MTV reduction associated with primary therapy outcome (MTV post-NACT p = 0.007, MTV reduction p = 0.001) and PFS (MTV post-NACT p = 0.005, MTV reduction p = 0.005). MTV reduction <85% identified the PD/SD patients (sensitivity 70%, specificity 78%, AUC 0.79). In a multivariate analysis, MTV reduction (p = 0.002) and FIGO stage (p = 0.003) were statistically significant variables associated with PFS. MTV reduction during NACT corresponded to OS (p = 0.05). CONCLUSION: 18F-FDG-PET/CT is helpful in NACT response evaluation. Patients with total MTV reduction <85% during NACT might be candidates for second-line chemotherapy and clinical trials, instead of interval debulking surgery.

LOW-DOSE CT PROTOCOL OPTIMIZATION FOR THE ASSESSMENT OF ACUTE APPENDICITIS: THE OPTICAP PHANTOM STUDY.

The aim was to evaluate effects of voltage, noise input (NI) and iterative reconstruction (IR) on radiation dose and image quality in order to establish a contrast enhanced low-dose protocol for assessment of acute appendicitis. An anthropomorphic abdominal phantom mimicking contrast enhanced abdomen was scanned with 80, 100 and 120 kV, standard and strong IR and 11 NIs (66 protocols). A total of 14 test tubes of increasing iodine dilutions and one tube with an appendicolith were evaluated within the phantom. The dose, HUs, noise, contrast-to-noise ratio (CNR) and figure of merit (FOM) were determined. Visual quality scores were assessed by two readers. A clinically used voltage-IR combination (120 kV, standard IR) was used as a reference. Overall, 100 kV with standard IR (p = 0.002) and 80 kV with both IRs (p < 0.001) showed higher CNR than the reference, but noise was most pronounced at 80 kV (p < 0.001). The highest FOM was found in the 100 kV protocols (p < 0.001). The reference and 100 kV with standard IR had highest image quality scores, where the 100 kV protocol enabled a distinct dose reduction. Lowering the voltage seems to be a more favorable tool than IR changes in optimizing the dose in contrast enhanced abdominal CT. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT01022567.

Is preoperative distinction between complicated and uncomplicated acute appendicitis feasible without imaging?

BACKGROUND: One of the main aims of appendicitis research is the differential diagnostics between complicated and uncomplicated acute appendicitis that enable provision of the optimal treatment for each patient. METHODS: Data in the present study were collected prospectively in our randomized antibiotic treatment for uncomplicated acute appendicitis trial (APPAC) comparing surgery and antibiotic treatment for uncomplicated acute appendicitis (NCT01022567). We evaluated 705 patients who had acute appendicitis on computed tomography. Patients with uncomplicated acute appendicitis (n = 368) were compared with all complicated acute appendicitis patients (n = 337), and subgroup analyses were performed between uncomplicated acute appendicitis and an appendicolith appendicitis (CA1; n = 256) and uncomplicated acute appendicitis and perforation and/or abscess (CA2; n = 78). Age, sex, body temperature (°C), duration of symptoms, white blood cell count (E9/L), and C-reactive protein (mg/L) were recorded on admission. Receiver operating characteristic curves were calculated for white blood cell count, C-reactive protein, and temperature. RESULTS: CA2 patients had significantly greater C-reactive protein levels (mean 122 and 47, respectively, P < .001) and longer duration of symptoms than uncomplicated acute appendicitis patients; 81% of CA2 patients and 38% of uncomplicated acute appendicitis patients had symptoms >24 hours before admission (P < .001). In receiver operating characteristic analysis, C-reactive protein and temperature had clinically significant results only in comparison with uncomplicated acute appendicitis and CA2 (area under the curve >0.7), but no optimum cutoff points could be identified. CONCLUSION: In clinical decision making, neither clinical findings nor laboratory markers are reliable enough to estimate the severity of the acute appendicitis accurately or to determine the presence of an appendicolith. The current results emphasize the role of computed tomography in the differential diagnosis of complicated and uncomplicated acute appendicitis.

Childhood predictors of adult fatty liver. The Cardiovascular Risk in Young Finns Study.

BACKGROUND & AIMS: Fatty liver is a potentially preventable cause of serious liver diseases. This longitudinal study aimed to identify childhood risk factors of fatty liver in adulthood in a population-based group of Finnish adults. METHODS: Study cohort included 2,042 individuals from the Cardiovascular Risk in Young Finns Study aged 3-18years at baseline in 1980. During the latest follow-up in 2011, the liver was scanned by ultrasound. In addition to physical and environmental factors related to fatty liver, we examined whether the genetic risk posed by a single nucleotide polymorphism in the patatin-like phospholipase domain-containing protein 3 gene (PNPLA3) (rs738409) strengthens prediction of adult fatty liver. RESULTS: Independent childhood predictors of adult fatty liver were small for gestational age, (odds ratio=1.71, 95% confidence interval=1.07-2.72), variant in PNPLA3 (1.63, 1.29-2.07 per one risk allele), variant in the transmembrane 6 superfamily 2 gene (TM6SF2) (1.57, 1.08-2.30), BMI (1.30, 1.07-1.59 per standard deviation) and insulin (1.25, 1.05-1.49 per standard deviation). Childhood blood pressure, physical activity, C-reactive protein, smoking, serum lipid levels or parental lifestyle factors did not predict fatty liver. Risk assessment based on childhood age, sex, BMI, insulin levels, birth weight, TM6SF2 and PNPLA3 was superior in predicting fatty liver compared with the approach using only age, sex, BMI and insulin levels (C statistics, 0.725 vs. 0.749; p=0.002). CONCLUSIONS: Childhood risk factors on the development of fatty liver were small for gestational age, high insulin and high BMI. Prediction of adult fatty liver was enhanced by taking into account genetic variants in PNPLA3 and TM6SF2 genes. LAY SUMMARY: The increase in pediatric obesity emphasizes the importance of identification of children and adolescents at high risk of fatty liver in adulthood. We used data from the longitudinal Cardiovascular Risk in Young Finns Study to examine the associations of childhood (3-18years) risk variables with fatty liver assessed in adulthood at the age of 34-49years. The findings suggest that a multifactorial approach with both lifestyle and genetic factors included would improve early identification of children with a high risk of adult fatty liver.

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.

Prevalence and determinants of fatty liver in normal-weight and overweight young adults. The Cardiovascular Risk in Young Finns Study.

BACKGROUND AND AIMS: Fatty liver may have different determinants in normal-weight and in obese individuals. We measured factors associated with fatty liver in 863 normal-weight (BMI < 25) and 1135 overweight/obese (BMI ≥ 25) young and middle-aged adults (45% male, age 34-49 years) in the population-based Cardiovascular Risk in Young Finns Study. METHODS AND RESULTS: The prevalence of fatty liver detected with ultrasound was 29% in overweight/obese and 5% in normal-weight participants. In overweight/obese, the independent correlates were waist circumference (odds ratio for 1 standard deviation increase = 3.78), alanine transaminase (2.11), BMI (2.00), male sex (1.74), triglycerides (1.44), systolic blood pressure (1.31), fasting insulin (1.23), and physical activity (0.76). In normal weight, the independent correlates included alanine transaminase (3.05), smoking (2.56), systolic blood pressure (1.54), and alcohol intake (1.41). In normal-weight participants, the associations with fatty liver were stronger for alcohol intake and smoking, and weaker for triglycerides, than in overweight/obese participants (P for interaction < 0.05). CONCLUSION: Prevalence of fatty liver was 29% in overweight/obese and 5% in normal-weight adults. Differences in factors associated with fatty liver were seen between these two groups: alcohol intake and smoking were more strongly and triglycerides more weakly associated in normal-weight than in overweight/obese participants.

Serum HE4 and CA125 as predictors of response and outcome during neoadjuvant chemotherapy of advanced high-grade serous ovarian cancer.

Human epididymis protein 4 (HE4) is a novel tumour marker in epithelial ovarian cancer (EOC). Data on its profile and predictive potential for subsequent outcome after neoadjuvant chemotherapy (NACT) are still under investigation. The aim of this study was to compare CA125 and HE4 profiles with radiologic response after NACT and to evaluate their potential as predictors of clinical outcome in a primarily inoperable EOC patient cohort. Twenty-five EOC patients of high-grade subtype (HGSC) treated with NACT were enrolled in the study. Serum HE4 and CA125 samples were taken at the time of diagnosis and before interval debulking surgery (IDS). Pre-NACT and pre-IDS HE4 and CA125 and their percentage changes were compared with NACT response seen on CT and surgical outcome in IDS. We also evaluated the biomarkers' abilities to predict platinum-free interval (PFI), progression-free survival (PFS) and overall survival (OS). All 25 patients were considered inoperable in laparoscopy at the time of diagnosis. HE4 and CA125 changes during NACT did not correlate with the changes seen on CT. Surgical outcome in IDS was associated with pre-IDS biomarker values but not with those taken before diagnosis. In IDS, 87 % had <1-cm residual tumour. In patients with HE4 change >80 and <80 % during NACT, the median OS was 3.38 and 1.60 years (p = 0.01), respectively. Serum HE4 is a promising additional tool when evaluating advanced HGSC patient's response to NACT. It may be helpful when deciding whether to proceed to IDS or to second-line chemotherapy.

Iron overload in allogeneic hematopoietic cell transplantation outcome: a meta-analysis.

An elevated ferritin level before allogeneic hematopoietic cell transplantation (HCT) is an adverse prognostic factor for overall survival (OS) and nonrelapse mortality. Because ferritin is an imperfect surrogate of iron stores, the prognostic role of iron overload remains unclear. We conducted a patient-level meta-analysis of 4 studies that used magnetic resonance imaging to estimate pre-HCT liver iron content (LIC). An elevated LIC was not associated with a significant increase in mortality: the hazard ratio (HR) for mortality associated with LIC > 7 mg/g dry weight (primary endpoint) was 1.4 (P = .18). In contrast, ferritin >1000 ng/mL was a significant prognostic factor (HR for mortality, 1.7; P = .036). There was, however, no significant association between ferritin > 2500 and mortality. This meta-analysis suggests that iron overload, as assessed by LIC, is not a strong prognostic factor for OS in a general adult HCT population. Our data also suggest that ferritin is an inadequate surrogate for iron overload in HCT.

[Computed tomographic colonography]. / Paksusuolen tietokonetomografia eli TT-kolografia.

Computed tomographic colonography, i.e. CT colonography has already widely replaced double-contrast colonography as a method of examination of the colon. A prerequisite of successful examination is a well-emptied and distended colon. CT colonography detects cancer with a sensitivity of 96%, which corresponds to the results of colonoscopy. Furthermore, CT colography allows the simultaneous assessment of the extracolonic organs in the abdominal cavity. The risk of bowel perforation is smaller than in conventional colonoscopy, and for the patient the CT examination is more convenient than conventional endoscopy or double-contrast colonography.

A prospective comparison of integrated FDG-PET/contrast-enhanced CT and contrast-enhanced CT for pretreatment imaging of advanced epithelial ovarian cancer.

OBJECTIVE: The use of tumor debulking surgery in the management of epithelial ovarian cancer (EOC), which is often disseminated in the peritoneal cavity at the time of diagnosis, has a significant impact on prognosis. We compared (18)F-fluorodeoxyglucose (FDG) positron emission tomography/contrast-enhanced computed tomography (PET/CT) to contrast-enhanced CT for the detection of dissemination into the abdominal cavity preventing successful primary debulking surgery. METHODS: Forty-one women with EOC underwent preoperative whole-body low-dose FDG-PET/CT followed by diagnostic high dose contrast-enhanced CT scan, and the results were compared with systematically recorded surgical findings as a reference standard. Both site-based and patient-based analyses were conducted. RESULTS: FDG-PET/CT was superior to conventional CT for the detection of carcinomatosis in subdiaphragmatic peritoneal surfaces (p=0.020) and in the bowel mesentery (p=0.001). Patient-based analysis of upper abdominal areas requiring extensive surgical procedures showed no significant differences between the two imaging methods. The sensitivity of PET/CT and CT was poor in certain areas of the peritoneal cavity (64% vs. 27% in the small bowel mesentery and 65% vs. 55% in the right upper abdomen). Extra-abdominal disease spread was detected by PET/CT in 32 patients and by CT in 25 patients. CONCLUSIONS: PET/CT was not superior to CT for the detection of intra-abdominal disease spread. Patients with suspected EOC should be referred for upfront radical surgery regardless of the results of preoperative imaging studies. PET/CT is more effective for the detection of extra-abdominal disease than CT, but the clinical significance of this finding is unclear.

Prognostic impact of pretransplant iron overload measured with magnetic resonance imaging on severe infections in allogeneic stem cell transplantation.

OBJECTIVE: Infections and graft-versus-host disease (GVHD) are the main causes of transplant-related mortality (TRM) of patients undergoing allo-SCT. The role of iron overload (IO) has been debated in this context. Studies, performed with non-specific surrogate markers of iron, suggest that IO predicts poor outcome after allo-SCT. METHODS: In this prospective study, we quantified pretransplant IO with MRI-based hepatic iron concentration (HIC) measurement; the degree of IO was used to predict infections, GVHD, and mortality after allo-SCT. Logistic univariate, multivariate, and Cox's regression analyses were performed. RESULTS: Iron overload was present in 78% of the patients (HIC>36 µmol/g). The median HIC was 98 µmol/g (range 5-348). There were no cases of cardiac iron excess. IO was significantly associated with severe infections during the early post-transplant period (for every 10 µmol/g increase OR: 1.15, 95% CI 1.05-1.26, P = 0.003). The odds for severe infections increased 6.5- (>125 µmol/g OR: 6.5, P = 0.013) to 14-fold (>269 µmol/g OR: 14.1, P = 0.040) with increasing HIC. IO was found to be associated with reduced risk of acute and chronic GVHD. Although TRM was due to infection-related deaths, IO was not associated with TRM or OS. CONCLUSION: Pretransplant IO, measured with a direct MRI-based measurement, predicts severe infections in the early post-transplant period.