Whole-body SPECT/CT for bone scintigraphy: diagnostic value and effect on patient management in oncological patients.

PURPOSE: This study was designed to assess the additional value of SPECT/CT of the trunk used in conjunction with conventional nuclear imaging and its effects on patient management in a large patient series. METHODS: In 353 patients, whole-body scintigraphy (WBS), SPECT, and SPECT/CT were prospectively performed for staging and restaging. SPECT/CT of the trunk was performed in all patients. In the 308 evaluable patients (211 with breast cancer, 97 with prostate cancer), clinical follow-up was used as the gold standard. Bone metastases were confirmed in 72 patients and excluded in 236. Multistep analyses per lesion and per patient were performed. Clinical relevance was expressed in terms of downstaging and upstaging rates on a per-patient basis. RESULTS: In the total patient group, sensitivities, specificities, and negative and positive predictive values on a per-patient basis were 93 %, 78 %, 95 % and 59 % for WBS, 94 %, 71 %, 97 % and 53 % for SPECT, and 97 %, 94 %, 97 % and 88 % for SPECT/CT, respectively. In all subgroups, specificity and positive predictive value were significantly (p<0.01) better with SPECT/CT. Downstaging of metastatic disease in the total, breast cancer and prostate cancer groups using SPECT/CT was possible in 32.1 %, 33.8 % and 29.5 % of patients, respectively. Upstaging in previously negative patients by additional SPECT/CT was observed in three breast cancer patients (2.1 %). Further diagnostic imaging procedures for unclear scintigraphic findings were necessary in only 2.5 % of patients. SPECT/CT improved diagnostic accuracy for defining the extent of multifocal metastatic disease in 34.6 % of these patients. CONCLUSIONS: SPECT/CT significantly improved the specificity and positive predictive value of bone scintigraphy in cancer patients. In breast cancer patients, we found a slight increase in sensitivity. SPECT/CT had a significant effect on clinical management because of correct downstaging and upstaging, better definition of the extent of metastases, and a reduction in further diagnostic procedures.

[Delayed effects of oncological therapy]. / Spätfolgen onkologischer Therapie.

Due to therapy-associated improvements in survival rates, delayed effects of cancer are a rapidly increasing but as yet only poorly recognized problem. These delayed sequelae, which by definition occur years after the primary disease, include secondary tumors and many non-oncological internal medical problems. Little attention has so far been paid to the cardiovascular, gastrointestinal, renal and endocrinal delayed side effects and must be specifically addressed due to the often slowly progressing symptoms.

[Medical technology and medical education]. / Medizintechnik in der ärztlichen Aus-, Weiter- und Fortbildung.

The education of medical professionals is divided into medical studies, postgraduate training leading to the qualification as a specialist, and continuing professional development. During education, all scientific knowledge and practical skills are to be acquired, which enable the physician to practice responsibly in a specialized medical area. In the present article, relevant curricula are analyzed regarding the consideration of medical device-related topics, as the clinical application of medical technology has reached a central position in modern patient care. Due to the enormous scientific and technical progress, this area has become as important as pharmacotherapy. Our evaluation shows that medical device-related topics are currently underrepresented in the course of medical education and training and should be given greater consideration in all areas of medical education. Possible solutions are presented.

[Evaluation of PET-CT : product safety, clinical usefulness, reimbursement in Germany and the USA]. / Bewertung der PET-CT : Produktsicherheit, klinischer Nutzen, Erstattung im deutschen und US-amerikanischen Gesundheitssystem.

Since 1994, PET - and later PET-CT - have gained significant clinical importance. Since 2002, PET-CT systems (PET + multislice CT) are available. The combination of high sensitivity PET images fused with high resolution CT images has gained widespread clinical acceptance for diagnosis, staging and re-staging as well as prediction of response to chemotherapy in oncology. Besides oncology, there are clear indications in diseases of the heart and the brain. The development of new systems in mainly based on multislice CT (64 slice). Radiopharmacology is advancing quickly, especially in the fields of oncology and neurological disorders. However, the limited reimbursement in Germany hampers this development.

A retrospective comparison of autologous and unrelated donor hematopoietic cell transplantation in myelodysplastic syndrome and secondary acute myeloid leukemia: a report on behalf of the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT).

Hematopoietic cell transplantation (HCT) is an effective treatment for myelodysplasia (MDS) and secondary acute myeloid leukemia (sAML). In this study, outcome of 593 patients with MDS/sAML after autologous and allogeneic HCT from a matched unrelated donor (MUD) were compared. A total of 167 (28%) patients received HCT from MUD without prior chemotherapy (MUD-U). The rest received HCT in first complete remission (CR1) (Autologous (Auto-CR1), n=290 (49%), HCT from MUD (MUD-CR1), n=136 (23%)). Survival at 3 years was best in MUD-CR1 (50%) compared to Auto-CR1 (41%) and MUD-U (40%) (P=0.01). Similarly, disease-free survival was 44% for MUD-CR1 compared to Auto-CR1 (28%) and MUD-U (34%) (P=0.03). Treatment-related mortality was 17% in Auto-CR1 compared to MUD-CR1 (38%) and MUD-U (49%) (P<0.001). Relapse for Auto-CR1 was 62% compared to 24 and 30% for MUD-CR1 and MUD-U, respectively (P<0.001). Outcome was best for patients with low tumor burden transplanted 6-12 months after diagnosis. Factors influencing outcome at 3 years were mainly significant in the first 6 months. Only, relapse after autologous HCT remained constant over time. Outcomes after allogeneic HCT in patients of 20-40 and >40 years were similar. Autologous and Allogeneic HCT from MUD offer the possibility of long-term survival to patients with MDS/sAML.

Analysis of functional domain organization in DNA topoisomerase II from humans and Saccharomyces cerevisiae.

The functional domain structure of human DNA topoisomerase IIalpha and Saccharomyces cerevisiae DNA topoisomerase II was studied by investigating the abilities of insertion and deletion mutant enzymes to support mitotic growth and catalyze transitions in DNA topology in vitro. Alignment of the human topoisomerase IIalpha and S. cerevisiae topoisomerase II sequences defined 13 conserved regions separated by less conserved or differently spaced sequences. The spatial tolerance of the spacer regions was addressed by insertion of linkers. The importance of the conserved regions was assessed through deletion of individual domains. We found that the exact spacing between most of the conserved domains is noncritical, as insertions in the spacer regions were tolerated with no influence on complementation ability. All conserved domains, however, are essential for sustained mitotic growth of S. cerevisiae and for enzymatic activity in vitro. A series of topoisomerase II carboxy-terminal truncations were investigated with respect to the ability to support viability, cellular localization, and enzymatic properties. The analysis showed that the divergent carboxy-terminal region of human topoisomerase IIalpha is dispensable for catalytic activity but contains elements that specifically locate the protein to the nucleus.

Incidental diagnosis of a PSA-negative prostate cancer by 18FDG PET/CT in a patient with hypopharyngeal cancer.

Diagnosis of prostate cancer (PC) still remains critical as non-invasive screening with prostate specific-antigen (PSA) lacks to indicate malignancy of the prostate in some cases. Recent research has shown that clinically meaningful PC can develop in patients with a PSA value <4 ng/ml, frequently defined as upper limit of normal serum PSA levels. Furthermore, both morphological (computed tomography (CT), magnetic resonance imaging, transrectal ultrasound) and functional imaging with (18)fluorodeoxyglucose positron emission tomography (FDG-PET) are associated with several limitations for primary diagnosis of PC. We report a case of an incidentally diagnosed PSA-negative PC by (18)FDG PET/CT in a patient with a previous diagnosis of a hypopharyngeal cancer.

Impact of thyroid metabolism on the course of INR levels in a patient with systemic anticoagulation suffering from amiodarone-induced thyrotoxicosis.

We report the case of a 60 year old female patient on continuous systemic anticoagulation therapy with coumarin due to mechanical aortic valve replacement and a more than 3 years lasting amiodarone therapy due to severe ventricular extrasystoles suffering from amiodarone induced thyrotoxicosis (AIT). During the course of AIT, showing different thyroid metabolic conditions, INR levels revealed a course closely related to the thyroid conditions indicating a significant and clear-cut effect of both hyper- and hypothyroidism on systemic anticoagulation therapy with coumarin. This continuous interaction of different thyroid metabolic conditions and the anticoagulation state could be well documented in the presented case over a time period of approximately five months.

Therapy of hepatocellular carcinoma with 131I-lipiodol: patient dosimetry.

AIM: Dosimetry in (131)I-lipiodol therapy for hepatocellular carcinoma (HCC) in the hitherto largest existing patient cohort. PATIENTS, METHODS: 38 courses of intra-arterial (131)I-lipiodol therapy with a total activity up to 6.7 GBq were performed in 18 patients with HCC. Liver and tumour volume were measured by computed tomography (CT) and (131)I-activity by scintigraphy on day 3, 6, 14, 28 and 42 after injection. Lipiodol deposition in tumour nodules as shown by CT rendered definite attachment to scintigraphic data possible. The radiation dose in tumour nodules, liver and lungs was calculated according to the MIRD concept and the tumour dose related to pre-therapeutic tumour volume, response and survival. RESULTS: Mean tumour dose was 23.6 +/- 3.6 Gy (14.2 +/- 2.1 mGy/MBq) with maximal 162 Gy (90.1 mGy/MBq) after one and 274 Gy after three courses. The dose to nontumourous liver was 1.9 +/- 0.2 Gy (1.2 +/- 0.1 mGy/MBq) and the mean dose ratio of tumour / nontumourous liver 11.1 +/- 1.7 (max. 82). The pulmonary dose was 25.9 +/- 1.8 mGy (16.3 +/- 1.2 microGy/MBq) and therefore much lower. There was a reciprocal relation between tumour dose and pretherapeutic tumour volume. Tumour dose had no effect on response or survival. CONCLUSION: High radiation doses are particularly in small tumour nodes achievable but not necessarily related to tumour response. The dose of non-tumourous liver and lungs is much lower.

Therapy of hepatocellular carcinoma with iodine-131-lipiodol. Results in a large German cohort.

AIM: To evaluate the efficacy and tolerance of iodine-131-lipiodol ((131)I-lipiodol) for hepatocellular carcinoma (HCC) in German long term patients and comparison with medically treated controls. PATIENTS, METHODS: 38 courses of intra-arterial (131)I-lipiodol therapy with a total activity up to 6.7 GBq were performed in 18 patients with HCC (6 with portal vein thrombosis). Liver and tumour volume and lipiodol deposition were measured by computed tomography and (131)I activity by scintigraphy. Therapeutic efficacy was determined by tumour volume change and matched-pairs analysis in comparison to medically (i.e. tamoxifen or medical support) treated patients. RESULTS: Tumour volume decreased in 20/32 index nodules (63%) after the first course. Repeated therapy frequently resulted in further tumour reduction. Overall response to treatment was partial in 11 nodules, minor response in 4 nodules, and disease was stable in 12 and progressive in 5. Significant response was associated with pretherapeutic nodule volume up to 150 ml (diameter of 6.6 cm). Survival rate after 3, 6, 9, 12, 24 and 36 months was 78, 61, 50, 39, 17, and 6%. Matched-pairs analysis of survival revealed (131)I-lipiodol to be superior to medical treatment. The most important side effect was a pancreatitis-like syndrome whereas overall tolerance was good. CONCLUSION: The long term results confirm that HCC therapy with (131)I-lipiodol is effective and probably superior to medical treatment. Tumour nodules of up to 6 cm diameter are well suited for this therapy even in the presence of portal vein thrombosis.

[Imaging, anatomic, and surgical considerations for rectal organs and function following radical resection of a rectal carcinoma]. / Unteres, kloakogenes Rektumviertel. Anatomie und chirurgische Bedeutung für Mastdarmvorfall, Inkontinenz, Rektozele und Radikaloperation beim Rektumkarzinom.

The distal quarter of the rectum is derived from the cloaca and can be viewed as a specialized "sensory organ". Only the proximal three quarters of the rectum stem phylogenetically from intestinal tissues. Therefore, only this upper portion has an associated mesorectum. A significant amount of data support the notion that profound differences exist between the enterogenic, upper segments and the cloacogenic, lower segment of the rectum: 1. differing supply with blood and lymph vessels, 2. embryologic and comparative anatomic findings, 3. the central support system provided by Denonvilliers' fascia, 4. specialized innervation, 5. malformations of the continence organ, 6. findings on magnetic resonance images and histologic macro sections, 7. findings on PET-CT images, 8. the muscular wall architecture of different portions of the rectum, 9. differences in basic function (storage vs continence), 10. location of most postoperative local recurrences of rectal carcinomas, even when complete mesorectal resection was performed, since hundred years.

[Technical limits of PET/CT with 18FDG in prostate cancer]. / Technische Grenzen des PET/CT mit 18FDG beim Adenokarzinom der Prostata.

There is increasing evidence that (18)FDG-PET is not useful for the imaging of primary prostate cancer. The aim of this examination was to prove whether or not these poor results are due to technical deficiencies of the examination method like older image reconstruction techniques, extensive (18)FDG-tracer activity in the bladder or improper contrast staining of the rectum. We examined three patients with primary prostate cancer using a modern combined PET/CT system, continuous irrigation of the bladder and an air-inflated rectal balloon catheter. PET/CT images show an exact depiction of both the prostate and all surrounding anatomic structures but no enhanced uptake of radiotracer in the tumour. Therefore, the mentioned poor results of (18)FDG-PET seem not to be due to technical deficiencies.

111In-Pentetreotide uptake in a follicular adenoma of the thyroid gland: a pitfall for 111In-Pentetreotide scintigraphy.

A patient with suspicion of a neuroendocrine tumor of the pancreas underwent a somatostatin receptor scintigraphy using 111In-Pentetreotide. 111In-pentetreotide scintigraphy showed discrete uptake of the radiotracer in the head of the pancreas and focal uptake in the right upper thyroid lobe. Tracer uptake in the 24h planar image was higher compared to the 4h image, and decreased after 48 hours. Normal thyroid tissue and thyroid disorders, such as cancers, Hashimoto's thyroiditis, and adenomas often show increased uptake of 111In-pentetreotide resulting in a possible false positive interpretation in patients with neuroendocrine tumor. Adding a 48h planar image might contribute to the differential diagnosis between benign or malignant lesions, as in the present case where the uptake decreased in an adenoma after 48 hours.

Immunological consolidation of ovarian carcinoma recurrences with monoclonal anti-idiotype antibody ACA125: immune responses and survival in palliative treatment. See The biology behind: K. A. Foon and M. Bhattacharya-Chatterjee, Are solid tumor anti-idiotype vaccines ready for prime time? Clin. Cancer Res., 7:1112-1115, 2001.

The aim of the present study was to assess whether the induction of specific immune responses by vaccination with the murine monoclonal anti-idiotypic antibody ACA125, which imitates the tumor-associated antigen CA125, has a positive influence on the survival of patients with recurrent ovarian carcinoma. Forty-two patients with platinum-pretreated recurrences were included in a clinical Phase I/II trial of consolidation in third-line therapy. Patients initially received four immunizations with 2 mg of alum-precipitated anti-idiotype ACA125 every 2 weeks and then monthly applications. No serious allergic reactions could be detected within a maximal control period of 56 months. Hyperimmune sera of 27 of 42 patients (64.2%) showed increased concentrations of human antimouse antibodies. Specific anti-anti-idiotypic antibodies as a marker for induced immunity were detected in 28 of 42 patients (66.7%). The survival of the whole ACA125-treated collective of patients after a mean of 12.6 antibody applications was 14.9 +/- 12.9 months. The survival of patients with a positive immune response was 19.9 +/- 13.1 months in contrast with 5.3 +/- 4.3 months in those patients without detectable anti-CA125 immunity (P < 0.0001). According to these results, vaccination with a suitable anti-idiotypic antibody offers an effective way to induce specific immunity against a primarily nonimmunogenic tumor antigen such as CA125 and is associated with a positive impact on the survival of patients with recurrent ovarian cancer with few side effects, which warrants a Phase III trial for ovarian cancer patients after primary therapy.

[PET-CT studies of the support system and continence function of pelvic organs. The pivotal importance of Denonvilliers' fascia for surgical procedures]. / PET-CT-Untersuchungen der Halterung und Kontinenz der Beckenorgane. Die Zentralstellung der Denonvilliers-Faszie -- Bedeutung für die chirurgische Therapie.

Like all other organs in the chest or abdominal cavities, pelvic organs are not suspended by specialized ligaments such as those in the skeletomuscular system. In spite of this, the organs of the pelvis remain well suspended within their cavity even during evacuation. This support system for these organs consists of inconspicuous smooth muscle elements scattered throughout pelvic structural fat tissue and fascial structures, in particular Denonvilliers' fascia. We used PET-CT studies to identify spontaneous muscle activity in the pelvis, which is strongest at Denonvilliers' fascia. We were able to correlate continence function, filling, and evacuation of pelvic organs with this spontaneous muscle activity that leads to stiffening and relaxation of the muscular walls of these organs. During the course of different disease processes such as visceral prolapse, these pelvic support structures are prone to fail gradually. Surgical interventions should take the pelvic support system into account to avoid therapeutic errors.

Discovery of rhenium and masurium (technetium) by Ida Noddack-Tacke and Walter Noddack. Forgotten heroes of nuclear medicine.

The history of the early identification of elements and their designation to the Mendeleev Table of the Elements was an important chapter in German science in which Ida (1896-1978) and Walter (1893-1960) Noddack played an important role in the first identification of rhenium (element 75, 1925) and technetium (element 43, 1933). In 1934 Ida Noddack was also the first to predict fission of uranium into smaller atoms. Although the Noddacks did not for some time later receive the recognition for the first identification of technetium-99m, their efforts have appropriately more recently been recognized. The discoveries of these early pioneers are even more astounding in light of the limited technologies and resources which were available during this period. The Noddack discoveries of elements 43 and 75 are related to the subsequent use of rhenium-188 (beta/gamma emitter) and technetium-99m (gamma emitter) in nuclear medicine. In particular, the theranostic relationship between these two generator-derived radioisotopes has been demonstrated and offers new opportunities in the current era of personalized medicine.

Introduction of a metabolic joint asymmetry score derived from conventional bone scintigraphy. A new tool to differentiate psoriatic from rheumatoid arthritis.

AIM: Clinical differentiation of psoriatic arthritis (PsA) and rheumatoid arthritis (rA) based on the pattern of joint involvement can be difficult; the frequent form of PsA with polyarthritis of the peripheral joints may sometime resemble rA. We investigated a metabolic joint asymmetry score (MJAS), reflecting the overall asymmetric joint involvement on conventional bone scintigraphy, for differentiating PsA from rA in patients presenting with peripheral polyarthritis. PATIENTS, METHODS: 106 patients (n = 61, PsA; n = 45, rA) with peripheral polyarthritis (≥ 5 joints) as well as 26 control subjects with no history of chronic joint disorders were analyzed. The intensity of articular 99mTc-MDP uptake in 40 peripheral joint pairs was scored regarding the bilateral difference of each joint based on a scale of 0-2 (no significant, moderate, and marked asymmetry, respectively). The patient's MJAS was defined as the sum of uptake difference scores of all joint pairs. The association of MJAS with the underlying condition (Psoriasis criteria, Revised Criteria of the ACR) was examined. RESULTS: 5280 peripheral joint pairs were investigated. There was no significant difference in the total number of involved joints in PsA 15.0 ± 8.2 versus rA 17.5 ± 8.8 patients (p = 0.132), but significantly less involvement in the control group (6.7 ± 5.0, p < 0.001). MJAS was markedly higher in PsA (17.0 ± 9.6) than in rA (4.8 ± 3.9, p < 0.001), and correlated with the total number of involved joints in PsA (r = 0.516, p < 0.001), but not in rA (r = 0.078, p = 0.380). The MJAS disparity between PsA and rA persisted after exclusion of the DIP joints (14.4 ± 7.7 vs. 4.4 ± 3.3; p<0.001). CONCLUSIONS: The new reproducible semi-quantification method for the asymmetry of metabolic joint involvement permits differentiation of psoriatic from rheumatoid peripheral arthritis with MJAS being markedly higher in patients with PsA as compared to rA patients. The score may offer an effective complementary tool for characterizing patients with peripheral polyarthritis.