Metastases In Normal-sized Nodes Research Articles

Detecting metastases in normal-sized pelvic lymph nodes in patients with bladder cancer: comparison of computed tomography and magnetic resonance imaging

Objective To estimate the diagnostic performance of computer tomography (CT) and magnetic resonance imaging (MRI) for detecting metastasis in pelvic lymph nodes with normal size in patients with bladder cancer. Methods Imaging of CT and MRI and clinical data of 118 patients who underwent radical cystectomy and pelvic lymphadenectomy were reviewed. The diagnostic efficacy of CT and MRI were analyzed when taking lymph nodes short axis diameter ≥0.3 cm and ≥1.0 cm respectively as diagnostic criterion of metastasis with correlation of pathological results. Results 22.7% (27/118) of patients were confirmed lymph nodes malignancies among 118 patients based on pathology. Totally 1 705 lymph nodes were detected in surgery and 119 of them were observed malignancy according to pathological presentation. The malignant nodes were mainly distributed in the perivesical (35.4%, 41/119), internal iliac (12.6%, 15/119), external iliac (30.3%, 36/119), obturator region (21.0%, 25/119) and presarcal region (1.7%, 2/119). Imaging of CT and MRI showed that when taking nodes with ≥0.3 cm in maximum short-axis diameter (MSAD) as positive, the sensitivity (Se), specificity (Sp), and positive predictive values (PPV) were 16.0%, 99.2%, 54.2% and 56.5%, 99.2%, 86.7% respectively. While taking MSAD≥1.0 cm as malignant, the Se, Sp and PPV of CT and MRI were 6.2%, 99.9%, 83.3% and 13%, 100%, 100% respectively. When taking MSAD ≥0.3 cm as positive, the Se and PPV between CT and MR were statistically different(P<0.001 and P=0.036, respectively). When taking MSAD ≥1.0 cm as positive, there was no statistically difference (P=0.275 and 1.000, respectively). Conclusions The incidence of normal-sized lymph node metastasis was higher in patients with bladder cancer. At this phase the MRI evaluation was superior to that of CT. When the MSAD ≥1.0 cm, there was no significant difference between CT and MRI. Key words: Bladder cancer; Lymph node metastasis; Computed tomography(CT); Magnetic resonance imaging(MRI); Diagnosis

Potential impact of 18F-FDG PET/CT on patients selection for neoadjuvant chemotherapy before radical cystectomy

BackgroundThe detection of lymph node metastases in bladder cancer has a major impact on treatment decisions and patients prognosis. Due to limited value of conventional imaging, the place of molecular and functional imaging needs to be precised, particularly in the neoadjuvant setting. MethodsFrom June 2011 to June 2013, 102 patients with clinically localized BCa were simultaneously staged with 18F-FDG PET/CT before RC. This study assessed the diagnostic accuracy of 18F-FDG PET/CT for the detection of metastases in normal-sized lymph nodes using extended pelvic lymph node dissection and histopathology as the reference standard. ResultsA total of 1211 LNs were examined histopathologically. Sixty-seven (5.5%) metastatic nodes were found in 26/102 patients (25.5%). Lymph node density was 22%. On patient-based analysis, sensitivity, specificity, predictive positive value (PPV), negative positive value (NPV) and accuracy for 18F-FDG PET/CT were calculated as 50%, 96.2%, 80%, 86.2% and 85.3% respectively. On a field-based analysis, sensitivity, specificity, PPV, NPV and accuracy for 18F-FDG PET/CT were calculated as 50.0%, 99.0%, 71.9%, 97.4%, and 96.5% respectively. The majority of missed metastases were micrometastasis <5 mm in long axis diameter. Conclusions18F-FDG PET/CT improves diagnostic efficacy for lymph node staging in patients staged N0 with conventional cross-sectional imaging. 18F-FDG PET/CT could be used as a surrogate marker for detection of metastases in non-enlarged pelvic lymph nodes and enhances management strategy guiding patients selection for neoadjuvant chemotherapy.

Lung Cancer: Morphological and Functional Approach to Screening, Staging and Treatment Planning

Lung cancer is a major problem in public health and constitutes the leading cause of cancer-related mortality in the world. Lung cancer screening with low-dose computed tomography is promising but needs to overcome many difficulties, such as the large number of incidentally discovered nodules, the radiation dose delivered to the patient during a whole screening program and its cost. The ultimate target point represented by the reduction of lung cancer-related mortality needs to be proved in large, well-designed, randomized, multicenter, prospective trials. Lung cancer staging by morphological tools seems to be limited owing to the presence of metastases in normal-sized lymph nodes. In this context, multidetector computed tomography cannot be used alone but is useful in conjunction with molecular imaging and MRI. Today, flurodeoxglucose PET-CT appears to be the most accurate method for lung cancer staging and may prevent unnecessary thoracotomies. For treatment planning, flurodeoxglucose PET-CT is playing an increasing role in radiotherapy planning at the target selection and definition steps.

Combined Ultrasmall Superparamagnetic Particles of Iron Oxide–Enhanced and Diffusion-Weighted Magnetic Resonance Imaging Reliably Detect Pelvic Lymph Node Metastases in Normal-Sized Nodes of Bladder and Prostate Cancer Patients

BackgroundLymph node staging of bladder or prostate cancer using conventional imaging is limited. Newer approaches such as ultrasmall superparamagnetic particles of iron oxide (USPIO) and diffusion-weighted magnetic resonance imaging (DW-MRI) have inconsistent diagnostic accuracy and are difficult to interpret. ObjectiveTo assess whether combined USPIO and DW-MRI (USPIO–DW-MRI) improves staging of normal-sized lymph nodes in bladder and/or prostate cancer patients. Design, setting, and participantsTwenty-one consecutive patients with bladder and/or prostate cancer were enrolled between May and October 2008. One patient was excluded secondary to bone metastases detected on DW-MRI with subsequent abstention from surgery. InterventionPatients preoperatively underwent 3-T MRI before and after administration of lymphotropic USPIO using conventional MRI sequences combined with DW-MRI. Surgery consisted of extended pelvic lymphadenectomy and resection of primary tumors. MeasurementsDiagnostic accuracies of the new combined USPIO–DW-MRI approach compared with the “classic” reading method evaluating USPIO images without and with DW-MRI versus histopathology were evaluated. Duration of the two reading methods was noted for each patient. Results and limitationsDiagnostic accuracy (90% per patient or per pelvic side) was comparable for the classic and the USPIO–DW-MRI reading method, while time of analysis with 80min (range 45–180min) for the classic and 13min (range 5–90min) for the USPIO–DW-MRI method was significantly shorter (p<0.0001). Interobserver agreement (three blinded readers) was high with a kappa value of 0.75 and 0.84, respectively. Histopathological analysis showed metastases in 26 of 802 analyzed lymph nodes (3.2%). Of these, 24 nodes (92%) were correctly diagnosed as positive on USPIO–DW-MRI. In two patients, one micrometastasis each (1.0×0.2mm; 0.7×0.4mm) was missed in all imaging studies. ConclusionsUSPIO–DW-MRI is a fast and accurate method for detecting pelvic lymph node metastases, even in normal-sized nodes of bladder or prostate cancer patients.

MRI with a lymph-node-specific contrast agent as an alternative to CT scan and lymph-node dissection in patients with prostate cancer: a prospective multicohort study

In patients with prostate cancer who are deemed to be at intermediate or high risk of having nodal metastases, invasive diagnostic pelvic lymph-node dissection (PLND) is the gold standard for the detection of nodal disease. However, a new lymph-node-specific MR-contrast agent ferumoxtran-10 can detect metastases in normal-sized nodes (ie, <8 mm in size) by use of MR lymphoangiography (MRL). In this prospective, multicentre cohort study, we aimed to compare the diagnostic accuracy of MRL with up-to-date multidetector CT (MDCT), and test the hypothesis that a negative MRL finding obviates the need for a PLND. We included consecutive patients with prostate cancer who had an intermediate or high risk (risk of >5% according to routinely used nomograms) of having lymph-node metastases. All patients were assessed by MDCT and MRL, and underwent PLND or fine-needle aspiration biopsy. Imaging results were correlated with histopathology. The primary outcomes were sensitivity, specificity, accuracy, NPV, and PPV of MRL and MDCT. This study is registered with ClinicalTrials.gov, number NCT00185029. The study was done in 11 hospitals in the Netherlands between April 8, 2003, and April 19, 2005. 375 consecutive patients were included. 61 of 375 (16%) patients had lymph-node metastases. Sensitivity was 34% (21 of 61; 95% CI 23-48) for MDCT and 82% (50 of 61; 70-90) for MRL (McNemar's test p<0.05). Specificity was 97% (303 of 314; 94-98) for MDCT and 93% (291 of 314; 89-95) for MRL. Positive predictive value (PPV) was 66% (21 of 32; 47-81) for MDCT and 69% (50 of 73; 56-79) for MRL. Negative predictive value (NPV) was 88% (303 of 343; 84-91) for MDCT and 96% (291 of 302; 93-98) for MRL (McNemar's test p<0.05). Of the 61 patients with lymph-node metastases, 50 were detected by MRL, of which 40 (80%) had metastases in normal-sized lymph nodes. The high sensitivity and NPV of MRL imply that in patients with a negative MRL, the chance of positive lymph nodes is less than 11/302 (4%). MRL had significantly higher sensitivity and NPV than MDCT for patients with prostate cancer who had intermediate or high risk of having lymph-node metastases. In such patients, after a negative MRL, the post-test probability of having lymph-node metastases is low enough to omit a PLND.

MR contrast agents in lymph node imaging

The detection of tumor metastases in lymph nodes is clinically important for tumor staging and therapy planning in cancer patients. However, differentiating between malignant and benign lymph nodes is still a problem because current imaging modalities rely only on the size and shape of the lymph nodes. Thus, small metastases in normal-sized lymph nodes can be missed, and it is difficult to differentiate enlarged nodes (benign hyperplasia versus malignant disease). Therefore, a specific lymphotropic contrast agent is needed to obtain a high contrast between functional and metastatic tissue. Contrast-enhanced MR lymphography is a noninvasive method for the analysis of the lymphatic system after interstitial (intracutaneous or subcutaneous) or intravenous application of contrast media. Interstitial MR lymphography using extracellular, liposomal, polymeric, lipophilic or particulate contrast agents results in high accumulation in regional lymph nodes. The systemic administration of a lymphotropic contrast medium is needed to address each individual lymph node. Ultrasmall superparamagnetic iron oxide particles are in late-stage clinical development for this indication, but they take 24 h to show sufficient contrast. Recently, a gadolinium-type contrast agent (Gadofluorine M) was described that detected lymph node metastases within 60 min of intravenous injection.

CT/MRI of nodal metastases in pelvic cancer

The accurate detection of lymph node metastases is one of the most important challenges in cancer imaging today, for the presence of nodal disease is a powerful adverse prognostic indicator. Pre-treatment detection of malignant nodes determines patient management, frequently distinguishing surgical candidates from those best suited to non-surgical therapy. However, the results of CT and MR imaging have been disappointing with poor sensitivities and specificities, low sensitivities being due to the inability to identify metastases in normal-sized nodes or those that are only minimally enlarged, and poor specificities resulting from nodal enlargement due to benign pathology. MR lymphography can demonstrate small nodal deposits, but the technique remains in the research arena, requires high-resolution thin sections to produce good image quality and is expensive. It is therefore likely to be used, at least for the foreseeable future, in highly selected patient groups. In order to give appropriate consideration to the likelihood of a prominent or enlarged lymph node harbouring a metastasis, it is incumbent on the radiologist to use all the relevant information available. This frequently requires discussion with clinicians or review of the patient’s case notes. In order to provide the best possible assessment of nodal status with CT and MR, the radiologist requires detailed knowledge of: (1) the primary tumour in terms of the patterns of spread and the incidence of nodal metastases at different stages of disease; (2) the characteristic CT/MR features of nodal involvement; (3) the pitfalls in diagnosis of nodal disease; (4) the accuracy of imaging and the impact of positive and negative results on patient management. The radiologist also needs information on the patient’s current therapy and previous treatment, as such knowledge may influence interpretation. For example, a patient who has previously been treated with pelvic radiotherapy is more likely to relapse in nodes outside the radiotherapy field, thus the development of nodal enlargement in the pelvis should be interpreted with caution. It is also important to know whether the patient has any coincidental disease that could be a cause of nodal enlargement.

Gadofluorine 8: initial experience with a new contrast medium for interstitial MR lymphography.

Differential diagnosis of malignant and beign lymph nodes is still a problem in lymphographic imaging modalities. Plain magnetic resonance imaging (MRI) and computed tomography (CT) are inadequate for detecting metastases in normal-sized lymph nodes and for differentiating enlarged nodes. Therefore it is important to have a contrast agent that accumulates in healthy lymphatic tissue but does not accumulate in metastatic deposits. The lymphographic contrast agent Gadofluorine 8 (Schering AG, Berlin, Germany) is a lipophilic but water-soluble gadolinium complex. Lymphographic effects were investigated in guinea pigs, dogs, and tumor-bearing rabbits after interstitial (subcutaneous or intracutaneous) injection. MR imaging was performed using T1-weighted gradient-echo sequences until 120 min after administration. After interstitial injection Gadofluorine 8 accumulates in regional lymph nodes, resulting in a pronounced increase in signal intensity in the lymph nodes. Differentiation between normal and metastatic lymph nodes was achieved. Gadofluorine 8 is an innovative contrast agent that can distinguish between normal and tumorous lymph nodes in interstitial MR lymphography.

Staging of genitourinary cancers. The role of diagnostic imaging.

Computed tomography (CT) is currently the standard modality for staging of urologic cancer in most institutions. It is used for demonstrating nodal involvement, and for demonstrating invasion of the primary lesion into surrounding fat, muscle, or other tissues or organs. It is also useful for demonstrating hepatic metastases in renal and vesical carcinomas. The problem with computed tomography, however, is that it can only show whether the nodes are large or not; neither can it show the nodal architecture, nor can it detect metastases in normal-sized nodes. Intravesical sonography has been helpful for staging papillary bladder cancer. Transrectal sonography has been somewhat helpful for demonstrating seminal vesicle invasion in patients with prostatic carcinoma. Inferior vena cavography and renal venography can be helpful for demonstrating whether a renal, renal pelvic, or adrenal carcinoma has extended into either vein. Lymphography can show nodal architecture and metastases in normal-sized nodes, and can make possible needle biopsy of abnormal-appearing nodes even if they are normal sized. The examination cannot show very small or microscopic nodal metastases, and it can miss abnormal nodes totally if they have been completely replaced by metastases. It yields false positives when fatty or fibrous infiltration of the nodes has occurred. It is used primarily for staging patients with testis or prostatic carcinoma. Bone scans are essential for staging prostatic carcinoma. Magnetic resonance imaging (MRI) is helpful in some cases of renal cell carcinoma. Multiplanar imaging prevents overstaging. It is also accurate for showing whether the renal vein or inferior vena cava are involved. Enlarged lymph nodes are easily distinguished from vessels. For staging bladder carcinoma involving the fundus or base of the bladder, MRI is better than CT. Microscopic nodal metastases, such as are common in carcinoma of the prostate, currently are not detected by any imaging modality.

Computed tomography in early stages of testicular carcinoma. Size of normal retroperitoneal lymph nodes and lymph nodes in patients with metastases in stage II A. A SWENOTECA study: Swedish-Norwegian Testicular Cancer Project.

From the SWENOTECA Project, the CT findings in 156 patients treated by bilateral retroperitoneal lymphadenectomy were reviewed. Of these, 112 were in stage I (no metastases) and 44 in stage II A (metastases in normal-sized lymph nodes and in nodes with a maximum diameter in the transverse plane of less than or equal to 20 mm). The normal size of lymph nodes in young Scandinavian men was found to be less than 10 mm X 8 mm above the bifurcation, except in the area below the left renal vein to the left of the aortic midline where the normal size was found to be maximally 14 mm X 10 mm. The addition of a lymphangiographic contrast medium did not change the size of the lymph nodes significantly above the bifurcation, while changes of importance were noticed in the pelvic area. Normal size without contrast medium was found to be at the most 15 mm X 10 mm and after addition of contrast medium to the nodes 28 mm X 12 mm. The results of the CT findings in the stage II A group were not impressive but changed somewhat for the better using the new limits concerning size of retroperitoneal lymph nodes. The impact of using different limits is discussed and it is concluded that metastases in normal-sized or almost normal-sized lymph nodes will continue to be a diagnostic problem, at least when using CT.