A prospective randomized controlled multicenter trial comparing antibiotic therapy with appendectomy in the treatment of uncomplicated acute appendicitis (APPAC trial).

BACKGROUND: Although the standard treatment of acute appendicitis (AA) consists of an early appendectomy, there has recently been both an interest and an increase in the use of antibiotic therapy as the primary treatment for uncomplicated AA. However, the use of antibiotic therapy in the treatment of uncomplicated AA is still controversial. METHODS/DESIGN: The APPAC trial is a randomized prospective controlled, open label, non-inferiority multicenter trial designed to compare antibiotic therapy (ertapenem) with emergency appendectomy in the treatment of uncomplicated AA. The primary endpoint of the study is the success of the randomized treatment. In the antibiotic treatment arm successful treatment is defined as being discharged from the hospital without the need for surgical intervention and no recurrent appendicitis during a minimum follow-up of one-year (treatment efficacy). Treatment efficacy in the operative treatment arm is defined as successful appendectomy evaluated to be 100%. Secondary endpoints are post-intervention complications, overall morbidity and mortality, the length of hospital stay and sick leave, treatment costs and pain scores (VAS, visual analoque scale). A maximum of 610 adult patients (aged 18-60 years) with a CT scan confirmed uncomplicated AA will be enrolled from six hospitals and randomized by a closed envelope method in a 1:1 ratio either to undergo emergency appendectomy or to receive ertapenem (1 g per day) for three days continued by oral levofloxacin (500 mg per day) plus metronidazole (1.5 g per day) for seven days. Follow-up by a telephone interview will be at 1 week, 2 months and 1, 3, 5 and 10 years; the primary and secondary endpoints of the trial will be evaluated at each time point. DISCUSSION: The APPAC trial aims to provide level I evidence to support the hypothesis that approximately 75-85% of patients with uncomplicated AA can be treated with effective antibiotic therapy avoiding unnecessary appendectomies and the related operative morbidity, also resulting in major cost savings.

FDG PET/CT in staging of advanced epithelial ovarian cancer: frequency of supradiaphragmatic lymph node metastasis challenges the traditional pattern of disease spread.

OBJECTIVE: Epithelial ovarian cancer (EOC) spreads intra-abdominally and to the retroperitoneal lymph nodes. A greater number of distant metastases are revealed by (18)F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) compared to conventional imaging methods. We aimed to investigate the presence and anatomic distribution of supradiaphragmatic lymph node metastasis (LNM) detected with pretreatment FDG PET/CT. METHODS: Thirty women with advanced stage (IIC-IV) EOC were scanned with whole body contrast-enhanced FDG PET/CT prior to surgery/neoadjuvant chemotherapy. We performed PET/CT analysis qualitatively and quantitatively. Additionally, contrast-enhanced CT was analyzed blinded to PET/CT scan. Intra-abdominal dissemination was verified by surgery and histopathology. Metabolically active lymph nodes were biopsied when possible. The clinical characteristics of patients with and without supradiaphragmatic LNM were compared. RESULTS: In 20/30 patients (67%) FDG PET/CT detected supradiaphragmatic LNM in one or more locations, whereas conventional CT found LNM in 10 patients (33%). Fourteen patients had parasternal, 14 cardiophrenic, 8 other mediastinal, 6 axillar, and 1 subclavian LNM. Microscopy of all four biopsied lymph nodes (three axillar and one subclavian) confirmed metastatic dissemination. The patients with supradiaphragmatic LNM had significantly more ascites (p<0.01), higher CA 125 levels, and more frequent subdiaphragmal carcinomatosis (p<0.03) compared to patients without supradiaphragmatic LNM in preoperative FDG PET/CT. CONCLUSIONS: A significant number of patients with advanced EOC showed supradiaphragmatic LNM in pre-treatment PET/CT. Our findings suggest that the route of EOC cells from the peritoneal cavity to the lymphatic system permeates the diaphragm mainly to the cardiophrenic and continues to parasternal lymph nodes.

Improved detection of localized prostate cancer using co-registered MRI and 11C-acetate PET/CT.

OBJECTIVES: We aimed to study the ability of contrast enhanced MRI at 1.5 T and 11C-acetate PET/CT, both individually and using fused data, to detect localized prostate cancer. METHODS: Thirty-six men with untreated prostate cancer and negative for metastatic disease on pelvic CT and bone scan were prospectively enrolled. A pelvic 11C-acetate PET/CT scan was performed in all patients, and a contrast enhanced MRI scan in 33 patients (6 examinations using both endorectal coil and surface coils, and 27 examinations using surface coils only). After the imaging studies 10 patients underwent prostatectomy and 26 were treated by image guided external beam radiation treatment. Image fusion of co-registered PET and MRI data was performed based on anatomical landmarks visible on CT and MRI using an advanced in-house developed software package. PET/CT, MRI and fused PET/MRI data were evaluated visually and compared with biopsy findings on a lobar level, while a sextant approach was used for patients undergoing prostatectomy. RESULTS: When using biopsy samples as method of reference, the sensitivity, specificity and accuracy for visual detection of prostate cancer on a lobar level by contrast enhanced MRI was 85%, 37%, 73% and that of 11C-acetate PET/CT 88%, 41%, 74%, respectively. Fusion of PET with MRI data increased sensitivity, specificity and accuracy to 90%, 72% and 85%, respectively. CONCLUSIONS: Fusion of sequentially obtained PET/CT and MRI data for the localization of prostate cancer is feasible and superior to the performance of each individual modality alone.

Serum HE4 Profile During Primary Chemotherapy of Epithelial Ovarian Cancer.

OBJECTIVE: Human epididymis protein 4 (HE4) is a promising novel serum biomarker for the detection of early-stage epithelial ovarian cancer (EOC) and for the differential diagnosis between benign and malignant ovarian tumors. The objective of the present study was to determine the value of HE4 for monitoring the response to primary therapy in patients with advanced disease. METHODS: Serum HE4 and cancer antigen (CA) 125 levels of 10 patients with advanced EOC and one patient with adenocarcinoma of unknown origin were measured preoperatively and during first-line chemotherapy. Seven patients were treated with primary surgery and six cycles of chemotherapy. Response to treatment was evaluated 4 weeks after the completion of chemotherapy using computed tomography. Four patients received neoadjuvant chemotherapy (NACT) before surgery. To evaluate the early response to chemotherapy, changes in serum biomarker levels were compared with metabolic changes of tumors during NACT as detected by positron emission tomography/computed tomography. RESULTS: The profile of HE4 during primary chemotherapy was in line with radiologic and clinical responses. In the neoadjuvant chemotherapy group, HE4 correlated better with the radiologic response than CA 125. CONCLUSION: Assessment of serum HE4 may improve the reliability of response evaluation during chemotherapy for serous epithelial ovarian cancer.

Functional imaging of localized prostate cancer aggressiveness using 11C-acetate PET/CT and 1H-MR spectroscopy.

UNLABELLED: We assessed the ability of (11)C-acetate PET/CT, MRI, and proton MR spectroscopy ((1)H-MRS) to image localized prostate cancer and detect its aggressiveness, using qualitative and quantitative approaches. METHODS: Twenty-one patients with untreated localized prostate cancer, diagnosed using transrectal ultrasound-guided biopsy, were prospectively enrolled. Cancer laterality was based on the percentage of cancer and the highest Gleason score determined from biopsies. In addition to PET/CT, 3-dimensional (1)H-MRS of the entire prostate volume using a quantitative approach was performed. The imaging and histologic findings of 8 patients undergoing subsequent prostatectomy were compared on a sextant level. For each lobe and sextant, standardized uptake values (SUVs) and (choline + creatine + polyamines)-to-citrate (CCP/C) ratios were obtained from (11)C-acetate PET/CT and (1)H-MRS, respectively. The visual and quantitative findings on PET/CT and MRI data were compared with cancer laterality and aggressiveness based on the Gleason score and with prostate-specific antigen (PSA) velocity and international risk group classification. RESULTS: The sensitivity, specificity, and accuracy, on a lobar level using visual analysis, of (11)C-acetate PET/CT were 80%, 29%, 71%, respectively, and 89%, 29%, 79%, respectively, using contrast-enhanced MRI. The sensitivity and accuracy of (11)C-acetate PET/CT decreased to 64% and 63% and specificity increased to 62% when sextant analysis was performed. The agreement between prostate cancer laterality based on biopsy findings and visual interpretation of (11)C-acetate PET/CT and contrast-enhanced MRI was similar at 71%. The mean SUV maximum and CCP/C maximum for the dominant tumor lesion were 5.5 and 1.48, respectively, and did not differ significantly from values in the nondominant lobe. The dominant-lesion SUVs or CCP/C values were not associated with histologically determined prostate cancer aggressiveness, nor did PSA velocity correlate with the SUV or CCP/C values from the entire gland. CONCLUSION: (11)C-acetate PET/CT, MRI, and (1)H-MRS enable detection of localized prostate cancer with comparable and limited accuracy but fail to provide information on cancer aggressiveness.

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 F-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.

Nonalcoholic fatty liver disease: rapid evaluation of liver fat content with in-phase and out-of-phase MR imaging.

PURPOSE: To evaluate in-phase and out-of-phase magnetic resonance (MR) imaging in the estimation of liver fat content (LFC) in patients with nonalcoholic fatty liver disease (NAFLD), with hydrogen ((1)H) MR spectroscopy as the reference standard. MATERIALS AND METHODS: Written informed consent was obtained from all subjects, and the local ethics committee approved this prospective study protocol. A total of 33 patients with type 2 diabetes mellitus who were at high risk for NAFLD (23 men, 10 women; overall mean age, 62.8 years +/- 8.3 [standard deviation]; age range, 48-77 years) underwent 1.5-T MR imaging with (1)H MR spectroscopy and in-phase and out-of-phase imaging of the liver. Three fat indexes were calculated from the signal intensity (SI) measured on the images. Two radiologists independently graded SI changes between in-phase and out-of-phase images by means of visual inspection. The Pearson correlation coefficient was used to study the relationship between the obtained parameters of SI change and LFC measured with (1)H MR spectroscopy. RESULTS: Fat indexes calculated from in-phase and out-of-phase images correlated linearly with LFC measured with (1)H MR spectroscopy (P < .001, r = 0.94-0.96) and were superior (P = .004) to visual estimates (P < .001, r = 0.88). The simple difference in SI between in-phase and out-of-phase images was used to calculate the fat index. An intercept of the regression line with the x-axis was observed at 5.1%, discriminating between normal and elevated LFC with high sensitivity (95%) and specificity (98%). CONCLUSION: In-phase and out-of-phase imaging can be used to rapidly estimate the LFC in patients with NAFLD. The cutoff value of 5.1% enables objective rapid and reliable discrimination of normal LFC from elevated LFC.