PET imaging urothelial bladder cancer: A novel approach.

443 Background: Urothelial bladder cancer (UBC) inflicts >80,000 new patients annually. Since treatment is stage-dependent, accurate staging is crucial. Conventional imaging and biopsy are often unreliable. A large number of PET tracers, developed to improve imaging, have limitations e.g. urinary excretion compromising their ability to assess the bladder lumen and invasive tumors. This study is to validate a hypothesis that high density VPAC receptors expression on UBC cell surface, can be targeted to PET image UBC, to determine loco-regional disease and metastatic lesions. Methods: Cu-64-TP3805 (4±10% mCi), with its high affinity (3.1 x 10−9M) for VPAC, was given IV to 19 UBC patients (44-80 yrs), scheduled for radical cystectomy. Those eligible for neoadjuvant chemotherapy were treated as such. Urine and blood samples were collected on the day of scan. Whole body PET/CT images acquired 60 to 90 min later and read by two physicians. Surgery was performed 1 to 4 weeks later. Imaging results were correlated with histology. Results: There were no adverse events. Urinary excretion of Cu-64-TP3805 was negligible. Blood clearance was biphasic (t ½ a = 22.3 ±2.7 min ~ 85% and t ½ β = 118.2 ± 4.9 min ~ 15%). VPAC PET bladder images were true positive (TP) in 11, true negative (TN) in 4, false positive (FP) in 1 and false negative (FN) in 3 patients with 79% sensitivity (95% CI 49%-95%), 80% specificity (95% CI 28%-100%), 92% PPV (95% CI 62%-100%), and 57% NPV (95% CI 18%-90%). Prostate images were TP in 8, TN in 6, and FP in 5 patients, with 100% sensitivity (95% CI 63%-100%), 55% specificity (95% CI 23%-83%), 62% PPV (95% CI 32%-86%), and 100% NPV (95% CI 54%-100%). The 5 FP images revealed HGPIN on re-analysis. For lymph nodes, images were TP in 1, TN in 14 and FN in 4 patients, with 25% sensitivity (95% CI 1%-81%), 100% specificity (95% CI 78%-100%), 100% PPV (95% CI 3%-100%), and 83% NPV (95% CI 59%-96%). In one patient, several lesions were seen in the spine and iliac crest. Biopsy was positive for metastasis. In smokers (N=12) there was diffused or focal tracer uptake in the lungs. In 7 non-smokers, 3 with CT depicted abnormality had tracer lung uptake and 4 did not. Conclusions: These first in human pilot study data depict Cu-64-TP3805 VPAC targeting to image UBC as worthy of further investigation.

The Acquired Von Willebrand Syndrome in Patients with Monoclonal IgA Proteins Is Rare but May be Clinically Severe

During the last 10 years our laboratory diagnosed and typed 5585 different patients with inherited von Willebrand disease (VWS) and acquired von Willebrand syndrome (aVWS). Out of these 21% (1217) suffered from aVWS. With 252 patients lymphoproliferative disorders were number three in frequency (21%) after cardiovascular (43%) and myeloproliferative (27%) disorders. Out of the patients with lymphoproliferative disorders patients with a monoclonal IgA protein comprised only 3.6% (9 patients). Much more abundant were monoclonal IgG´s (71%) and IgM´s (26%). According to our data only one patient was classified as MGUS and the others suffered from myeloma. The most impressive property was the heterogeneity of their laboratory and clinical data with the exception that all patients suffered from severe bleeding complications whenever their hemostatic system was challenged by accidents or invasive procedures (even iliac crest biopsy). The VWF:Ag ranged from 0.06 – 5.60 IU/ml and only one patient had a VWF:Ag <0.5 IU/dl. The functional test (VWF:CB) ranged from 0.06 and 5.48 IU/ml again with only one patient <0.5 IU/dl. The ratio VWF:CB / VWF:Ag was below 0.8 in three patients. Thus more than 50% of the patients would remain undetected if the VWF multimers were not included in the diagnostic panel. Two patients displayed the whole set of multimers, while the others showed a mild (5) or severe (2) absence of the large multimers. The hallmark of the multimic pattern from patients with an IgA monoclonal protein was the presence of a lot of smeary material within the electrophoretic lanes diplayed in all patients. In summary aVWS in the course of lymphoproliferative disorders and monoclonal IgA proteins is clinically severe, although probably not life threatening. It remains undetected with standard VWF tests and might be therefore not as rare as detected in our large patient panel. Disclosures No relevant conflicts of interest to declare.

Clinical observations in cutan mastocytosis

Introduction: Mastocytosis is a clonal mast cell proliferative disease, devided into cutaneous and systemic forms. The characteristic symptoms are caused by neoplastic mast cell infiltrations in different organs and/or the release of mediators. Aim: The aim of the authors was to summarize their clinical observations in patients with mastocytosis. Method: 22 adult patients diagnosed consecutively with mastocytosis were enrolled in the study. Skin and bone marrow biopsies were taken to establish the diagnosis and perform c-KIT mutation (D816V) analysis. Results: One of the 22 patients had teleangiectasia macularis eruptiva perstans, while 20/22 patients had urticaria pigmentosa. All patients had cutaneous lesions. In 12 patients iliac crest biopsy was performed and 9 of them had bone marrow involvement, classified as indolent systemic mastocytosis. The c-kit mutation D816V was found in one subject both in skin and bone marrow samples. The patients were treated with antihistamine, PUVA, interferon-α or imatinib. Conclusions: The authors draw attention to this rare disease in order to help recognition of relevant signs and symptoms and establish an early diagnosis. Orv. Hetil., 2013, 154, 1469–1475.

Jamshidi needle Biopsy of the Sternal Bone Marrow.

Abstract 4548 The aspiration and biopsy of the bone marrow is one of the most valuable and important tests in hematology, oncology and medicine. It is a high yield, safe, fast and informative test performed frequently in medical practice with minimal complications. For reasons of ease and safety, bone marrow aspiration and biopsy are usually obtained from the posterior iliac crest. I reviewed my experience in obtaining 37 consecutive bone marrow biopsies from the sternum using a Jamshidi needle (gauge 11; external diameter 3.048 mm) in 36 consecutive patients (twice in one patient) over a 9 year period, in whom a posterior iliac crest study could not be done. Technique After performing the sternal bone marrow aspiration in the usual manner, a small skin incision is made over the sternum with a scalpel. The Jamshidi needle is introduced at approximately a 90 degree angle in the middle of the sternum at the level of the 3rd intercostal space. After a ”give” is felt, indicating that the needle has reached the bone marrow cavity, the tip of the needle is angled downwards at 45 degrees or less and with a clockwise - counterclockwise movement, the needle is advanced for 3 to 10 mm. After a slight change of angle aiming at “breaking” the distal attachment of the bone marrow piece, the needle is slowly withdrawn with the same rotatory movements. In no case did I feel that I had reached the inner table of the sternum. All patients were observed and examined 20 minutes and 24 hours after the procedure. Results There were 22 inpatient and 15 outpatient procedures. The reasons that precluded the performance of the preferred posterior iliac crest bone marrow biopsy were: immobility in 17 patients, obesity in 13, prior radiation in 3 and other in 4. The final diagnosis was a malignant disorder in 17 patients (leukemia, lymphoma, myelodysplasia, plasma cell dyscrasia or metastatic cancer). All but one were new diagnoses. In 20 cases the final diagnosis was a benign hematological disorder or a non diagnostic bone marrow examination. In 9 occasions (mostly obese patients and patients with prior radiation therapy) a previous attempt at performing a posterior iliac crest biopsy had failed. The only complications were the development of a tumor nodule in the needle tract in one patient with an aggressive, Burkitt's type lymphoma and a small superficial hematoma in a patient with a highly vascular metastatic breast cancer. The bone marrow core biopsy of the sternum, performed as described, in the hands of an experienced practitioner is a safe and helpful test in the evaluation of the bone marrow cytology, architecture and anatomy in selected patients in whom the performance of the preferred posterior iliac crest biopsy cannot be done. Disclosures: No relevant conflicts of interest to declare.