Dimitris J. Apostolopoulos

Increased Serum CA-15.3 Levels in Patients with Megaloblastic Anemia due to Vitamin B12 Deficiency

Objectives: To estimate the usefulness of serum tumor markers’ monitoring, as predictors of gastric cancer in patients with pernicious anemia. Patients and Methods: We investigated serum levels of carcinoembryonic antigen (CEA), α-fetal protein, cancer antigen (CA)-19.9, CA-125 and CA-15.3 in 50 patients with pernicious anemia and in 24 healthy controls, matched for age and sex. In 38 patients, the evaluation was repeated 1–6 months after the correction of cobalamin deficiency. Results: All patients and controls had normal serum CEA and α-FP, and the levels of these markers as well as those of CA-125 and CA-19.9 did not differ between the two groups. All 50 patients, but only 2 controls exhibited increased serum CA-15.3, and the difference between the two groups was very significant (129.4 ± 84.9 vs. 19.8 ± 7.3 IU/ml, p < 0.001), while no difference between males and females was found. A thorough clinical examination of all patients, and mammographic study in 18 females did not reveal any finding suspicious of breast cancer. CA-15.3 levels were positively correlated with serum lactate dehydrogenase, and negatively with B12 and hemoglobin, but they were substantially decreased after the correction of anemia, in all 38 patients tested, and in 33 of them they were restored to normal. After a median follow-up of 34 months, one patient developed a colon cancer, but none showed any sign suspicious of breast cancer. Conclusions: Serum CA-15.3 shows an aberrant increase in untreated patients with pernicious anemia, which is reversed after the correction of the anemia. The possible origin seems unrelated to mammary tissue, and may be released by the apoptosing bone marrow megaloblastic erythroblasts.

Atypical bilateral stress fractures of the femoral shaft diagnosed by bone scintigraphy in a woman with osteoporosis.

Recent case series have identified the presence of atypical insufficiency fractures at the diaphyseal femur of osteoporotic patients, which are possibly related to the long-term use of biphosphonates. We present images of a 72-year-old woman with a history of colon cancer and osteoporosis referred for bone scintigraphy because of bilateral thigh pain. No trauma or intense exercise was reported. Bone scan revealed bilateral femoral shaft stress fractures, which were confirmed by plain radiographs. In oncologic patients with osteoporosis referred for bone scintigraphy, atypical stress fractures should be included in the differential diagnosis of focal findings in the diaphyseal femur.

Treating Iodine Deficiency: Long-Term Effects of Iodine Repletion on Growth and Pubertal Development in School-Age Children

BACKGROUND Iodine deficiency (ID) is still a major universal health problem. Iodine deficiency disorders (IDDs) affect people of all ages, among whom the most vulnerable are children and adolescents. The aim of the present study was to assess the long-term effects on growth and pubertal development of correcting severe ID in areas of Azerbaijan between 1999 and 2000. METHODS Iodized oil was administered orally to 293,000 children, aged 6-16 years. Among those, 364 children were randomly selected and were examined 1 year before the administration of iodized oil (Group I-neg, iodine negative) and 295 children (Group I-Rx, iodine treated) were examined 4 years (Group I-R x 4, iodine treated 4 years later; n = 173) or 5 years (Group I-R x 5, iodine treated 5 years later; n = 122) after the last dose of iodide. RESULTS In Group I-neg the median urine iodine concentration (UIC) (mcg/L) was 36 (mean: 36.272 +/- 11.036) and increased significantly (p < 0.001) in Group I-R x 4: 188 (mean: 230.969 +/- 155.818) and in Group I-R x 5: 175 (mean: 201.176 +/- 130.369). The prevalence of goiter was 99% in Group I-neg and 2% in Group I-R x 4. Children in Group I-Rx had a greater standard deviation score (SDS) for height (-0.1364 +/- 1.279, n = 294) than children in Group I-neg (-0.5019 +/- 1.17, n = 363) (p < 0.001, t = -3.817), which was more significant for boys. SDS for weight was similar in both groups (Group I-neg: -0.17 +/- 0.78, n = 363; Group I-Rx: -0.115 +/- 0.917, n = 294). The rate of puberty development as judged by the development of breast and pubic hair was normalized in both sexes after the correction of ID. CONCLUSIONS Our results demonstrate that long-term correction of severe ID leads to sustained improvement of linear growth accompanied by a normalization of the time of onset of pubertal development for both sexes.

Tc-99m Depreotide SPECT/CT depicts myocardial involvement in a case of thrombotic thrombocytopenic purpura.

We report a case of thrombotic thrombocytopenic purpura (TTP) with cardiac involvement, imaged with Tc-99m depreotide. A 56-year-old man presented with fever, hematuria, and chest pain. Laboratory findings (angiopathic hemolytic anemia, thrombocytopenia, and uremia) were suggestive of TTP. Cardiac enzymes were elevated and diffuse left ventricular hypokinesis was demonstrated by echocardiography. Serum rheumatologic and virologic analysis were negative. A Tc-99m depreotide SPECT/CT study showed diffuse uptake in the myocardium, indicating inflammatory reaction to thrombotic/hemorrhagic myocardial damage. We suggest that Tc-99m depreotide imaging may reveal myocardial involvement in TTP; this could prompt further investigation for potential applications in myocarditis of other etiologies.

Bone scintigraphy depicts bilateral atypical femoral stress fractures with metachronous presentation, long before a complete fracture occurs

Atypical femoral fractures (AFF), although rare, are recognized more often during the last decade. They are located in the subtrochanteric region or the femoral shaft, may be bilateral, can evolve to complete fractures after bone overload or minimal trauma and have specific radiological features. The complete fractures have horizontal or slightly oblique configuration accompanied by a medial spike, are non-comminuted, and extend to both cortices. There is also generalized cortical thickening of femoral shaft. Newer evidence suggests that AFF are stress or insufficiency fractures, possibly associated with long-term use of bisphoshonates (BP). AFF can also occur in oncologic patients referred for bone scintigraphy and, in such a case, they should be differentiated from bone metastases. We present here a case with bilateral AFF with metachronous appearance in a female patient with a history of breast cancer and osteoporosis. The first AFF had been depicted on bone scintigraphy 3 years before a complete fracture occurred at this site, but the finding was overlooked. A second bone scan performed shortly after the fracture in order to exclude underlying bone metastases disclosed an additional unsuspected incomplete AFF in the contralateral femur, which was confirmed by radiography. In conclusion, oncologists should consider other causes of bone pain besides bone metastatic disease, and physicians interpreting whole body bone scans of oncologic patients should be aware of the entity of AFF, in order to avoid false positive results and provide early information about an impending complete AFF.

Technetium-99m depreotide imaging by single photon emission tomography/low resolution computed tomography in malignant lymphomas: comparison with gallium-67 citrate

ObjectivePrevious studies have demonstrated the feasibility of targeting lymphoma lesions with somatostatin receptor binding agents, mainly with In-111-pentetreotide. In the present work another somatostatin analog, Tc-99m depreotide, is investigated.MethodsOne-hundred and six patients, 47 with Hodgkin’s (HL) and 59 with various types of non-Hodgkin’s lymphoma (NHL), were imaged with both Tc-99m depreotide and Ga-67 citrate. Planar whole-body and single photon emission tomography/low resolution computerized tomography (SPECT/CT) images were obtained. A total of 142 examinations were undertaken at different phases of the disease. Depreotide and gallium findings were compared visually and semi-quantitatively, with reference to the results of conventional work-up and the patients’ follow-up data.ResultsIn most HL, intermediate- and low-grade B-cell, as well as in T-cell NHL, depreotide depicted more lesions than Ga-67 and/or exhibited higher tumor uptake. The opposite was true in aggressive B-cell NHL. However, there were notable exceptions in all lymphoma subtypes. During initial staging, 93.3% of affected lymph nodes above the diaphragm, 100% of inguinal nodes and all cases with splenic infiltration were detected by depreotide. On the basis of depreotide findings, 32% of patients with early-stage HL were upstaged. However, advanced HL and NHL cases were frequently downstaged, due to low sensitivity for abdominal lymph node (22.7%), liver (45.5%) and bone marrow involvement (36.4%). Post-therapy, depreotide detected 94.7% of cases with refractory disease or recurrence. Its overall specificity was moderate (57.1%). Rebound thymic hyperplasia, various inflammatory processes and sites of unspecific uptake were the commonest causes of false positive findings. The combination of depreotide and gallium enhanced sensitivity (100%), while various false positive results of either agent could be avoided.ConclusionExcept perhaps for early-stage HL, Tc-99m depreotide as a stand-alone imaging modality has limited value for the initial staging of lymphomas. Post-therapy, however, depreotide scintigraphy seems useful in the evaluation of certain anatomic areas, particularly in non-aggressive lymphoma types. The combination with Ga-67 potentially enhances sensitivity and specificity. If fluorodeoxyglucose positron emission tomography is not available or in case of certain indolent lymphoma types, Tc-99m depreotide may have a role as an adjunct to conventional imaging procedures.

Comparison between 180 degrees and 360 degrees acquisition arcs with and without correction by CT-based attenuation maps in normal hearts at rest.

ObjectiveTo investigate the effect of acquisition arc (180° or 360°) and attenuation correction (AC), in artifact occurrence and image uniformity of myocardial perfusion SPECT studies in normal hearts. MethodsTwenty male and 44 female patients with primary hyperparathyroidism and low probability of resting perfusion abnormalities were analysed. 99mTc-sestamibi myocardial perfusion studies were performed at rest with a hybrid SPECT/CT system. An anthropomorphic phantom was also imaged. ResultsWithout AC, a 360° orbit resulted in significantly lower artifact rates compared to the standard 180° in both gender groups. Differences persisted (P<0.001) even after adjusting reconstruction filter settings to compensate for disproportionate count statistics between the two arcs. However, gender-related variation was not considerably decreased and sub-diaphragmatic activity was augmented with a 360° arc. After AC with either arc, substantially lower defect scores and minimal gender-related differences were obtained compared to the standard technique. A 360° arc yielded lower defect rates and count variability than did the 180° arc (P<0.05). These differences were small and were eliminated after weighting for dissimilar count statistics. Sub-diaphragmatic signal was amplified, particularly with 360°; severe bowel–myocardial activity overlap complicated image interpretation in 14% of cases with 360° versus 8% with 180°. In certain aspects, phantom imaging findings diverged from patient studies. ConclusionWithout AC there is significant disparity between 180° and 360° concerning artifact occurrence. After CT-based AC differences between arcs in defect rate and image uniformity seem less critical. However, 180° is favoured by less intensification of intestinal activity.

The impact of transmission-emission misregistration on the interpretation of SPET/CT myocardial perfusion studies and the value of misregistration correction

OBJECTIVE Previous studies indicate that the quality of single photon emission tomography/computed tomography (SPET/CT) myocardial perfusion imaging (MPI) is degraded by even mild transmission-emission misregistrations. The purpose of the current study was to investigate the impact of SPET/CT misalignment on the interpretation of MPI and examine the value of a commercial software application for registration correction. SUBJECTS AND METHODS A total of 255 technetium-99m ((99m)Tc)-tetrofosmin stress/rest MPI examinations in 150 patients were reviewed for SPET/CT misalignment. After registration correction by the software, images were reassessed for interpretation differences from the misregistered study. The diagnostic benefit of reregistration was determined by taking into account the non-attenuation compensated image pattern, combined stress-rest evaluation, gated-SPET data and patients history. In a phantom experiment and in 3 representative clinical cases, SPET/CT misalignment was purposely created by the software by sequential slice shifts and its effect was evaluated quantitatively. RESULTS Misregistration ≥1 pixel in at least one direction was observed in 24% of studies. Interpretation of MPI changed after registration correction in 11% of cases with misalignment <1 pixel, in 18% with 1-2 and in 73% with ≥2 pixels. The diagnostic information seemed to improve after registration correction in 58% of studies irrespective of the degree of misregistration. Software-simulated misregistration had dissimilar effects in the phantom and the 3 selected clinical cases. CONCLUSIONS The impact of SPET/CT misregistration on MPI interpretation although influenced by the degree and direction of slice misplacement, it is also case-specific and hardly predictable. Registration restoration by the software seems worthwhile regardless of misregistration magnitude.

(99m)Tc sestamibi as a prognostic factor of response to first-line therapy and outcome in patients with malignant lymphoma.

Introduction Resistance to chemotherapy poses a major problem in cancer patients. Although of multifactorial origin, some of the implicated mechanisms also interfere with 99mTc-MIBI uptake and retention in cancer cells. The aim of the current study was to investigate the prognostic value of baseline 99mTc-MIBI imaging in lymphoma. Methods 99mTc-MIBI SPECT was performed in 16 patients with Hodgkin lymphoma and 31 with non-Hodgkin lymphoma (NHL) before chemotherapy initiation. Early (20 minutes), late (120 minutes) tumor-to-background (T/B) ratios, and 2-hour 99mTc-MIBI washout were calculated. Follow-up data were obtained for a period of 45.5 ± 23.5 months. Study end points were response to first-line chemotherapy, lymphoma-related death (LRD), and time to disease progression. Results Of the scintigraphic indices examined, the late T/B ratio correlated best with study end points. A cutoff value of 1.8 determined by receiver operating characteristic analysis discriminated poor from good response and LRD from survival with an accuracy of 87% and 81%, respectively. Kaplan-Meier survivor functions separated by this cutoff differed significantly for both time to disease progression and LRD (P = 0.0001 and P = 0.0015). In the Cox proportional hazards model, the late T/B ratio proved to have an independent and incremental value over clinical prognostic factors (age, lymphoma type, Ann Arbor stage, lactate dehydrogenase levels) and, in NHL patients, over the international prognostic index. Patients with high international prognostic index score could be further stratified into different prognostic categories. Conclusion The current study indicates that baseline 99mTc-MIBI SPECT can provide useful prognostic information in patients with lymphoma, particularly NHL, regarding therapy response and final outcome.