Lindsay Brammen

Extraordinary Lymph Drainage in Cutaneous Malignant Melanoma and the Value of Hybrid Imaging: A Case Report

In melanoma patients, preoperative lymphoscintigraphy has become a gold standard. The role of single-photon emission computed tomography (SPECT) or its combination with computed tomography (SPECT-CT) as part of the standard sentinel scintigraphy protocol has yet to be determined. A 46-year-old female patient with melanoma of the trunk received preoperative lymphoscintigraphy and subsequent surgical excision. Planar imaging displayed two hot spots in the region of the primary lesion. No other lymphatic flow pathways could be appreciated. Two focal hot spots, one dorsal to the primary lesion near the left latissimus dorsi muscle and one just lateral to the primary lesion in the subcutaneous tissue, were appreciated with SPECT-CT imaging. The primary melanoma lesion, as well as the two additional lesions, which were detected by SPECT-CT, were excised and sent for histopathological examination. While the primary lesion was a superficial spreading melanoma, the lesions appreciated in SPECT-CT revealed four sentinel lymph nodes, each of which was negative for tumor cells. Melanomas, especially of the trunk, can demonstrate multiple lymphatic drain basins in a large percentage of patients. Given that without the detailed anatomical information provided by SPECT-CT it would be very difficult to locate the diverse lymphatic drain basins and their lymph nodes, we would suggest routinely implementing SPECT-CT in the standard planar sentinel imaging protocol.

Sentinel lymph node detection in vulvar cancer patients: a 20 years analysis.

Our study aimed to analyze postoperative treatment-related morbidity after sentinel lymph node biopsy (SLNB) compared to systematic inguinofemoral lymph node dissection (ILND) and the recurrence rate in patients with vulvar cancer. This single center study included 128 patients diagnosed with vulvar cancer that underwent ILND or SLNB between January 1991 - January 2011 with intraoperative SLN detection and removal. Treatment-related morbidity, as well as recurrence rate of SLNB patients were evaluated. Preoperative sentinel node scintigraphy was successful in 82/89 (92%) of the patients. A hundred and seventy six nodes were visualized and all positive SLN were detected within 60min. Patients who were treated with ILND underwent a longer operation (P<0.001), required longer inguinal drainage (P<0.001), and had a lengthier postoperative hospital stay (P=0.006). The presence of lymph cysts (P=0.02, 95% CI 3.4 (1-1-10.6) was significantly higher in ILND patients. No groin recurrence was appreciated in SLNB patients. In conclusion, patients who underwent SLNB were at a lower risk of postoperative morbidity. No groin recurrences were observed in patients who received SLNB.

A retrospective analysis of the accuracy of radioactively labeled autologous leukocytes in patients with infected prosthetic joints

BACKGROUND Labeled leukocyte scintigraphy (LS) is considered a valuable tool in preoperative diagnosis of prosthetic joint infections (PJI). The aim of this study was to determine the accuracy of LS combined with bone marrow scintigraphy (BMS), as well as inflammation markers CRP and WBC, in detecting infection in patients with prosthetic joints. MATERIAL AND METHODS This study included patients suspected of having PJI between January and September 2013 at the Vienna General Hospital who underwent imaging with 99mTc-HMPAO labeled autologous leukocytes and subsequent BMS. Diagnostic accuracy was assessed in terms of sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). RESULTS A total of 48 patients were included. The most common joint investigated was knee (25), followed by hip (9), shoulder (2), and elbow (1). Other parts of the body investigated included the femur (6), tibia (2), leg (2), and foot (1). The pathogens most frequently isolated included Staphylococcus epidermidis and Candida albicans. The sensitivity of LS was 60%, specificity 97%, PPV 86% and NPV 90%. Overall accuracy was calculated to be 90%. CONCLUSIONS This study was able to demonstrate that 99mTc-HMPAO labeled autologous leukocytes in patients presenting with symptoms of PJI is accurate. In contrast, however, inflammation markers CRP and WBC are not accurate pre-diagnostic markers for PJI.

Molecular imaging of atherosclerotic lesions by positron emission tomography - can it meet the expectations?

Early non-invasive imaging of atherosclerosis and in particular the detection of lesions at risk with high specificity could significantly affect cardiovascular morbidity and mortality. Conventional nuclear medicine approaches, in particular using autologous radiolabeled lipoproteins, can be related to histopathological findings; however, they fail to identify lesions at risk. Positron emission tomography (PET) tracers with much better physical properties have been examined, the most detailed information being available for F-18-deoxyglucose (FDG) and F-18-sodium fluoride (NaF). These two approaches are sensitive to different biochemical mechanisms, i.e. inflammation and microcalcification. Initial enthusiasm, in particular for F-18-FDG, has disappeared, although for F-18-NaF there is some hope, but this is not a breakthrough. No tracer is available so far that is able to identify a specific characteristic of a lesion prone to rupture. Other PET tracers in the pipeline have been examined, mainly in experimental models and only a few in patients, but they failed to contribute significantly to early lesion discovery and do not support great expectations. The key question is: Do we understand what we see? Moreover, methodological problems, a lack of standardization of imaging protocols and aspects of quantification provide a wide range for potential future improvements. While monitoring a therapeutic intervention seems to be possible for both F-18-FDG and F-18-NaF, highly specific early identification of lesions at risk by PET imaging is still far away. As of today, PET is not ready for routine clinical judgment of atherosclerotic lesions at risk to rupture. Even if all these problems can be solved, radiation exposure will still remain a concern, in particular for repeated studies.

TP53 is not a prognostic marker-clinical consequences of a generally disregarded fact: How to bring a biomarker to clinical use

Technological progress within the last 15–20 years has significantly increased our knowledge about the molecular basis of cancer development, tumor progression, and treatment response. As a consequence, a vast number of biomarkers have been proposed, but only a small fraction of them have found their way into clinical use. The aim of this paper is to describe the specific demands a clinically relevant biomarker should meet and how biomarkers can be tested stepwise. We name this procedure the “triple‐R principle”: robustness, reproducibility, and relevance. The usefulness of this principle is illustrated with the marker TP53. Since it is mutated in a broad spectrum of cancer entities, TP53 can be considered a very promising marker. Thus, TP53 has been studied in detail but there is still no explicit consensus about its clinical value. By considering our own experience and reviewing the literature, we demonstrate that a major problem of current biomarker research is disregard of whether the biomarker is prognostic or predictive. As an example, it is demonstrated that TP53 is not a prognostic marker, but rather a purely predictive marker, and that disregard of this fact has made this otherwise strong biomarker appear as not being clinically useful so far.

The effect of elevated lipoprotein(a) on autologous platelets function: a retrospective analysis.

OBJECTIVE Platelet labeling is used to study platelets in vivo in terms of diagnosing intravascular thrombosis, as well as studying their role and biological activity in atherosclerosis. A low labeling efficiency (LE) can negatively impair testing results. Labeling efficiency depends on various factors, including low-density-lipoprotein (LDL)-cholesterol levels in the blood. Lipoprotein(a) (Lp(a)) is a lipoprotein subclass that when elevated, is frequently associated with the premature development of cardiovascular disease through activation of different signaling pathways and cell surface receptors. SUBJECTS AND METHODS We retrospectively studied 51 patients with isolated elevated Lp(a) (>50 mg/dL, ranging up to 440 mg/dL) compared to patients with normal lipid profiles who underwent autologous radioactive platelet labeling during the time period of January 2001-September 2013 at the Vienna General Hospital. Platelets were radiolabeled according to ISORBE consensus. RESULTS LE was decreased in patients with elevated Lp(a). Cross-incubation of hyper-Lp(a) patients with normal Lp(a) plasma and vice versa demonstrated that platelets themselves and not the plasmatic environment are accountable for the decline in LE. Furthermore, LE positively correlated with an increase in platelet incubation time, the highest LE being seen after 30 minutes. CONCLUSION This study determined that extremely elevated Lp(a) profiles, especially values greater than 150 mg/dL, may significantly impair platelets function such as labeling results. Platelets are responsible for the decrease in LE in hyper-Lp(a) patients. Non-HDL-Lp is the most informative parameter of impaired LE. We thus recommend to include Lp(a) in the list of parameters that need to be taken into consideration in studying autologous radiolabeled platelets.

Accuracy of radioactively labeled autologous leukocytes in patients with infected prosthetic joints.

Objective: A serious complication of joint replacement surgery is infection, which results in prolonged invalidity due to decrease in joint function and hospitalization, often resulting in removal and subsequent re-implantation after lengthy antibiotic therapy. Labeled leukocyte scintigraphy (LS) is considered a valuable tool in preoperative diagnosis of prosthetic joint infections. The aim of this study was to examine imaging of in vitro radioactively labeled autologous leukocytes and bone marrow scans in their accuracy and reliability in detecting infection in patients with prosthetic joints. Furthermore, inflammation markers CRP and WBC count were analyzed for their accuracy in detecting prosthetic joint infection. Methods: This single center study included all patients suspected of having prosthetic joint infections between January and September 2013 at the Vienna General Hospital. A total of 45 mL blood was drawn from a peripheral vein and leukocytes were radioactively labeled with Tc-99m-HMPAO according to protocol. The labeled leukocytes were then re-injected into a peripheral vein. A whole body scintigraphy and local images were recorded with a double-headed gamma camera four hours after re-injection. Additional local images were taken taken approximately 24 hours following re-injection. In the case of positive LS, bone marrow scintigraphy was conducted 48 hours after re-injection. Local images were recorded 30 minutes after injection of 370 MBq Tc-99m-nanocolloid. Results: This study included a total of 50 patients. All the patients underwent subsequent bacterial and histological testing via joint aspiration or operation of the joint. The most common joint investigated was knee (27), followed by hip (9), shoulder (2), and elbow (1). Other cases involved the complete femur (6), tibia (2), leg (2), and foot (1). Pathogens isolated from the joints included Staphylococcus epidermidis and Candida albicans. The sensitivity of LS was 63%, specificity 90%, PPV 56% and NPV 93%. Overall accuracy was calculated to be 86%. Pre-diagnostic testing with CRP and WBC was conducted in 43 patients. Mean CRP was 3,9 mg/dl. Thirty-one patients had a CRP-level higher and 12 patients lower than the cut-off. The sensitivity was 57%, specificity 28%, PPV 13%, NPV 77% and accuracy 33%. Lastly, only 3 patients had WBC counts higher than the cut-off. WBC count had a sensitivity of 0%, specificity 92%, PPV 0%, NPV 88% and overall accuracy 82%. Conclusion: While this study showed that CRP and WBC are not accurate pre-diagnostic markers for prosthetic joint infection, it was able to demonstrate that Tc-99m-HMPAO labeled autologous leukocytes in patients presenting with symptoms of prosthetic joint infection is accurate. LS is a feasible imaging method in patients with infection of prosthetic joints and may