Maarten S. van Leeuwen

A Step-up Approach or Open Necrosectomy for Necrotizing Pancreatitis

BACKGROUND Necrotizing pancreatitis with infected necrotic tissue is associated with a high rate of complications and death. Standard treatment is open necrosectomy. The outcome may be improved by a minimally invasive step-up approach. METHODS In this multicenter study, we randomly assigned 88 patients with necrotizing pancreatitis and suspected or confirmed infected necrotic tissue to undergo primary open necrosectomy or a step-up approach to treatment. The step-up approach consisted of percutaneous drainage followed, if necessary, by minimally invasive retroperitoneal necrosectomy. The primary end point was a composite of major complications (new-onset multiple-organ failure or multiple systemic complications, perforation of a visceral organ or enterocutaneous fistula, or bleeding) or death. RESULTS The primary end point occurred in 31 of 45 patients (69%) assigned to open necrosectomy and in 17 of 43 patients (40%) assigned to the step-up approach (risk ratio with the step-up approach, 0.57; 95% confidence interval, 0.38 to 0.87; P=0.006). Of the patients assigned to the step-up approach, 35% were treated with percutaneous drainage only. New-onset multiple-organ failure occurred less often in patients assigned to the step-up approach than in those assigned to open necrosectomy (12% vs. 40%, P=0.002). The rate of death did not differ significantly between groups (19% vs. 16%, P=0.70). Patients assigned to the step-up approach had a lower rate of incisional hernias (7% vs. 24%, P=0.03) and new-onset diabetes (16% vs. 38%, P=0.02). CONCLUSIONS A minimally invasive step-up approach, as compared with open necrosectomy, reduced the rate of the composite end point of major complications or death among patients with necrotizing pancreatitis and infected necrotic tissue. (Current Controlled Trials number, ISRCTN13975868.)

Perfusion-CT Assessment of Infarct Core and Penumbra: Receiver Operating Characteristic Curve Analysis in 130 Patients Suspected of Acute Hemispheric Stroke

Background and Purpose— Different definitions have been proposed to define the ischemic penumbra from perfusion-CT (PCT) data, based on parameters and thresholds tested only in small pilot studies. The purpose of this study was to perform a systematic evaluation of all PCT parameters (cerebral blood flow, volume [CBV], mean transit time [MTT], time-to-peak) in a large series of acute stroke patients, to determine which (combination of) parameters most accurately predicts infarct and penumbra. Methods— One hundred and thirty patients with symptoms suggesting hemispheric stroke ≤12 hours from onset were enrolled in a prospective multicenter trial. They all underwent admission PCT and follow-up diffusion-weighted imaging/fluid-attenuated inversion recovery (DWI/FLAIR); 25 patients also underwent admission DWI/FLAIR. PCT maps were assessed for absolute and relative reduced CBV, reduced cerebral blood flow, increased MTT, and increased time-to-peak. Receiver-operating characteristic curve analysis was performed to determine the most accurate PCT parameter, and the optimal threshold for each parameter, using DWI/FLAIR as the gold standard. Results— The PCT parameter that most accurately describes the tissue at risk of infarction in case of persistent arterial occlusion is the relative MTT (area under the curve=0.962), with an optimal threshold of 145%. The PCT parameter that most accurately describes the infarct core on admission is the absolute CBV (area under the curve=0.927), with an optimal threshold at 2.0 ml×100 g−1. Conclusion— In a large series of 130 patients, the optimal approach to define the infarct and the penumbra is a combined approach using 2 PCT parameters: relative MTT and absolute CBV, with dedicated thresholds.

Reproducibility of In Vivo Carotid Intima-Media Thickness Measurements A Review

BACKGROUND The early phase of atherosclerosis can be studied by two-dimensional B-mode ultrasonography. Measurements of the combined thickness of the carotid intima and media arc currently used as intermediate outcome in clinical trials. Comparison of results between studies is difficult because of the different methods of image acquisition and analysis used. We review these methods and the reported reproducibility of intima-media thickness (IMT) measurements. SUMMARY OF REVIEW Articles were collected using the MEDLINE literature search system and the references in the selected articles. Literature concerning human in vivo IMT measurements published in the English language in the period 1991 through 1995 was reviewed. A description of the methods of measuring IMT to determine intraobserver and/or interobserver variability was a prerequisite for inclusion. Twenty-three studies were included. Best reproducibility was found when measuring the mean IMT in the common carotid artery in more than one direction. CONCLUSIONS We conclude that a consensus concerning the assessment of IMT is urgently needed. Variability of IMT measurements is lowest when determining the mean thickness in the common carotid artery in different directions.

Imaging strategies for detection of urgent conditions in patients with acute abdominal pain: diagnostic accuracy study

Objective To identify an optimal imaging strategy for the accurate detection of urgent conditions in patients with acute abdominal pain. Design Fully paired multicentre diagnostic accuracy study with prospective data collection. Setting Emergency departments of two university hospitals and four large teaching hospitals in the Netherlands. Participants 1021 patients with non-traumatic abdominal pain of >2 hours’ and <5 days’ duration. Exclusion criteria were discharge from the emergency department with no imaging considered warranted by the treating physician, pregnancy, and haemorrhagic shock. Intervention All patients had plain radiographs (upright chest and supine abdominal), ultrasonography, and computed tomography (CT) after clinical and laboratory examination. A panel of experienced physicians assigned a final diagnosis after six months and classified the condition as urgent or non-urgent. Main outcome measures Sensitivity and specificity for urgent conditions, percentage of missed cases and false positives, and exposure to radiation for single imaging strategies, conditional imaging strategies (CT after initial ultrasonography), and strategies driven by body mass index and age or by location of pain. Results 661 (65%) patients had a final diagnosis classified as urgent. The initial clinical diagnosis resulted in many false positive urgent diagnoses, which were significantly reduced after ultrasonography or CT. CT detected more urgent diagnoses than did ultrasonography: sensitivity was 89% (95% confidence interval 87% to 92%) for CT and 70% (67% to 74%) for ultrasonography (P<0.001). A conditional strategy with CT only after negative or inconclusive ultrasonography yielded the highest sensitivity, missing only 6% of urgent cases. With this strategy, only 49% (46% to 52%) of patients would have CT. Alternative strategies guided by body mass index, age, or location of the pain would all result in a loss of sensitivity. Conclusion Although CT is the most sensitive imaging investigation for detecting urgent conditions in patients with abdominal pain, using ultrasonography first and CT only in those with negative or inconclusive ultrasonography results in the best sensitivity and lowers exposure to radiation.

Waiting times for radiotherapy: consequences of volume increase for the TCP in oropharyngeal carcinoma

BACKGROUND AND PURPOSE Waiting lists for radiotherapy have become longer over the past years. Apart from the psychological distress for the patient we are concerned about tumour growth during this waiting time, which may worsen prognosis. The purpose of this pilot study was to investigate tumour growth in the waiting time and to obtain an indication of its clinical consequences for patients with oropharyngeal carcinoma. A tumour control probability (TCP) model was applied to evaluate consequences for outcome. METHODS AND MATERIALS Increase in tumour volume was measured for 13 patients with oropharyngeal carcinoma by outlining the tumour on the diagnostic as well as on the treatment planning CT scan. Waiting time was defined as time between histopathological diagnosis and start of radiotherapy. For each tumour we calculated the increase in tumour volume and the tumour doubling time. The potential increase in TCP was calculated for each tumour for the situation without treatment delay. RESULTS The mean increase in tumour volume was 70%. The mean waiting time was 56 days. Expected TCP with incorporation of delay was 47%, without delay it might have been 63-66%. CONCLUSION This study shows tumour progression during the time between the diagnostic CT scan and the treatment planning CT scan in oropharyngeal cancer. As a consequence of waiting time, which allows tumour volume increase, there may be an average control loss of 16-19 % for these tumours during the total waiting time before radiotherapy.

Robot-assisted minimally invasive thoraco-laparoscopic esophagectomy versus open transthoracic esophagectomy for resectable esophageal cancer, a randomized controlled trial (ROBOT trial)

BackgroundFor esophageal cancer patients, radical esophagolymphadenectomy is the cornerstone of multimodality treatment with curative intent. Transthoracic esophagectomy is the preferred surgical approach worldwide allowing for en-bloc resection of the tumor with the surrounding lymph nodes. However, the percentage of cardiopulmonary complications associated with the transthoracic approach is high (50 to 70%).Recent studies have shown that robot-assisted minimally invasive thoraco-laparoscopic esophagectomy (RATE) is at least equivalent to the open transthoracic approach for esophageal cancer in terms of short-term oncological outcomes. RATE was accompanied with reduced blood loss, shorter ICU stay and improved lymph node retrieval compared with open esophagectomy, and the pulmonary complication rate, hospital stay and perioperative mortality were comparable. The objective is to evaluate the efficacy, risks, quality of life and cost-effectiveness of RATE as an alternative to open transthoracic esophagectomy for treatment of esophageal cancer.Methods/designThis is an investigator-initiated and investigator-driven monocenter randomized controlled parallel-group, superiority trial. All adult patients (age ≥18 and ≤80 years) with histologically proven, surgically resectable (cT1-4a, N0-3, M0) esophageal carcinoma of the intrathoracic esophagus and with European Clinical Oncology Group performance status 0, 1 or 2 will be assessed for eligibility and included after obtaining informed consent. Patients (n = 112) with resectable esophageal cancer are randomized in the outpatient department to either RATE (n = 56) or open three-stage transthoracic esophageal resection (n = 56). The primary outcome of this study is the percentage of overall complications (grade 2 and higher) as stated by the modified Clavien–Dindo classification of surgical complications.DiscussionThis is the first randomized controlled trial designed to compare RATE with open transthoracic esophagectomy as surgical treatment for resectable esophageal cancer. If our hypothesis is proven correct, RATE will result in a lower percentage of postoperative complications, lower blood loss, and shorter hospital stay, but with at least similar oncologic outcomes and better postoperative quality of life compared with open transthoracic esophagectomy. The study started in January 2012. Follow-up will be 5 years. Short-term results will be analyzed and published after discharge of the last randomized patient.Trial registrationDutch trial register: NTR3291 ClinicalTrial.gov: NCT01544790

Newly Diagnosed Lymphoma: Initial Results With Whole-Body T1-Weighted, STIR, and Diffusion-Weighted MRI Compared With 18F-FDG PET/CT

OBJECTIVE The purpose of this study was to compare whole-body MRI including diffusion-weighted imaging (DWI) with (18)F-FDG PET/CT in the staging of newly diagnosed lymphoma. SUBJECTS AND METHODS Twenty-two consecutively registered patients with newly diagnosed lymphoma prospectively underwent whole-body MRI (22 with T1-weighted, STIR, and DWI sequences and 21 with T1-weighted and STIR sequences but not DWI) and FDG PET/CT. Whole-body MRI-DWI was independently evaluated by two blinded observers. Interobserver agreement was assessed, and whole-body MRI-DWI was compared with FDG PET/CT. RESULTS The kappa values for interobserver agreement on whole-body MRI-DWI for all nodal regions together and for all extranodal regions together were 0.676 and 0.452. The kappa values for agreement between whole-body MRI-DWI and FDG PET/CT for all nodal regions together and for all extranodal regions together were 0.597 and 0.507. Ann Arbor stage according to whole-body MRI-DWI findings was concordant with that of FDG PET/CT findings in 77% (17/22) of patients. Understaging and overstaging relative to the findings with FDG PET/CT occurred in 0% (0/22) and 23% (5/22) of cases. In the care of 9% (2/22) of patients, overstaging with whole-body MRI-DWI relative to staging with FDG PET/CT would have had therapeutic consequences. CONCLUSION Our early results indicate that overall interobserver agreement on whole-body MRI-DWI findings is moderate to good. Overall agreement between whole-body MRI-DWI and FDG PET/CT is moderate. In the care of patients with newly diagnosed lymphoma, staging with whole-body MRI-DWI does not result in underestimation of stage relative to the results with FDG PET/CT. In a minority of patients, reliance on whole-body MRI-DWI leads to clinically important overstaging relative to the results with FDG PET/CT. FDG PET/CT remains the reference standard for lymphoma staging until larger-scale studies show that use of whole-body MRI-DWI results in correct staging in this minority of cases.

Perimesencephalic Hemorrhage Exclusion of Vertebrobasilar Aneurysms With CT Angiography

BACKGROUND AND PURPOSE It is important to recognize a perimesencephalic pattern of hemorrhage in patients with subarachnoid hemorrhage (SAH), because in 95% of these patients the cause is nonaneurysmal and the prognosis is excellent. The purpose of this study was to investigate whether CT angiography can accurately exclude vertebrobasilar aneurysms in patients with perimesencephalic patterns of hemorrhage and therefore replace digital subtraction angiography (DSA) in this setting. METHODS In 40 patients with posterior fossa SAH as shown on unenhanced CT, 2 radiologists independently evaluated unenhanced CT for distinguishing between perimesencephalic and nonperimesencephalic pattern of hemorrhage and assessed CT angiography for detection of aneurysms. All patients subsequently underwent DSA or autopsy. RESULTS Observers agreed in 38 of 40 patients (95%) in differentiating perimesencephalic and nonperimesencephalic patterns of hemorrhage on unenhanced CT. On the CT angiograms, both observers detected a vertebrobasilar aneurysm in 16 patients and no aneurysm in 24 patients. These findings were confirmed by DSA or autopsy. No patients with a perimesencephalic pattern of hemorrhage were found to have an aneurysm on either CT angiography or DSA. CONCLUSIONS Good recognition of a perimesencephalic pattern of hemorrhage is possible on unenhanced CT, and CT angiography accurately excludes and detects vertebrobasilar aneurysms. DSA can be withheld in patients with a perimesencephalic pattern of hemorrhage and negative CT angiography.

Preoperative Imaging of Colorectal Liver Metastases After Neoadjuvant Chemotherapy: A Meta-Analysis

BackgroundChemotherapy treatment induces parenchymal changes that potentially affect imaging of CRLM. The purpose of this meta-analysis was to provide values of diagnostic performance of magnetic resonance imaging (MRI), computed tomography (CT), fluorodeoxyglucose positron emission tomography (FDG-PET), and FDG-PET/CT for preoperative detection of colorectal liver metastases (CRLM) in patients treated with neoadjuvant chemotherapy.MethodsA comprehensive search was performed for original articles published from inception to 2011 assessing diagnostic performance of MRI, CT, FDG-PET, or FDG-PET/CT for preoperative evaluation of CRLM following chemotherapy. Intraoperative findings and/or histology were used as reference standard. For each imaging modality we calculated pooled sensitivities for patients who received neoadjuvant chemotherapy as well as for chemonaive patients, defined as number of malignant lesions detected divided by number of malignant lesions as confirmed by the reference standard.ResultsA total of 11 papers, comprising 223 patients with 906 lesions, were included. Substantial variation in study design, patient characteristics, imaging features, and reference tests was observed. Pooled sensitivity estimates of MRI, CT, FDG-PET, and FDG-PET/CT were 85.7% (69.7–94.0%), 69.9% (65.6–73.9%), 54.5% (46.7–62.1%), and 51.7% (37.8–65.4%), respectively. In chemonaive patients, sensitivity rates were 80.5% (67.0–89.4%) for CT, 81.3% (64.1–91.4%) for FDG-PET, and 71.0% (64.3–76.9%) for FDG-PET/CT. Specificity could not be calculated because of non-reporting of “true negative lesions.”ConclusionIn the neoadjuvant setting, MRI appears to be the most appropriate imaging modality for preoperative assessment of patients with CRLM. CT is the second-best diagnostic modality and should be used in the absence of MRI. Diagnostic accuracy of FDG-PET and PET-CT is strongly affected by chemotherapy.

A rational approach to dose reduction in CT: individualized scan protocols

The aim of this study was to demonstrate that dose reduction and constant image quality can be achieved by adjusting X-ray dose to patient size. To establish the relation between patient size, image quality and dose we scanned 19 patients with reduced dose. Image noise was measured. Four radiologists scored image quality subjectively, whereby a higher score meant less image quality. A reference patient diameter was determined for which the dose was just sufficient. Then 22 patients were scanned with the X-ray dose adjusted to their size. Again, image noise was measured and subjective image quality was scored. The dose reduction compared with the standard protocol was calculated. In the first group the measured noise was correlated to the patient diameter (ρ=0.78). This correlation is lost in the second group (ρ=–0.13). The correlation between patient diameter and subjective image quality scores changes from ρ=0.60 (group 1) to ρ=–0.69 (group 2). Compared with the standard protocol, the dose was reduced (mean 28%, range 0–76%) in 19 of 22 patients (86%). Dose reduction and constant noise can be achieved when the X-ray dose is adjusted to the patient diameter. With constant image noise the subjective image quality increases with larger patients.