Survival after 131I-labeled lipiodol therapy for hepatocellular carcinoma. A single-center study based on a long-term follow-up.

UNLABELLED: This study investigated the efficacy of 131iodine-labeled lipiodol (131I-lipiodol) as a palliative therapy, evaluated overall survival (OS) across Barcelona Clinic Liver Cancer (BCLC) stages, and determined the main prognostic factors influencing OS in patients with hepatocellular carcinoma (HCC). PATIENTS, METHODS: We retrospectively analyzed 57 (44 men; mean age, 65.7 years; mean activity per session, 1.6 GBq; mean cumulative activity in patients with >1 sessions, 3.9 GBq) HCC patients who underwent 131I-lipiodol therapy. A majority of patients exhibited Child-Pugh class B (53.6%) disease and a good Eastern Cooperative Oncology Group performance status (0-1; 72%). Multinodular disease was observed in 87.7% patients, bilobar disease in 73%, and portal vein occlusion (PVO) in 54%. Furthermore, 21.1% patients were staged as BCLC B and 59.6 % as BCLC C. All patients were followed until death. RESULTS: The median OS was 6.4 months, which varied significantly with disease stage (median OS for BCLC A, B, C, and D was 29.4, 12.0, 4.6, and 2.7 months, respectively; p = 0.009); Child-Pugh score and class; presence of ascites, PVO, or extrahepatic disease; largest lesion size; favourable treatment response; international normalized ratio, baseline albumin and alpha-fetoprotein levels. Patients with a Child-Pugh A liver disease had a longer OS. CONCLUSION: Currently, different treatment modalities for HCC include radioembolization, transarterial chemoembolization, and systemic therapy with sorafenib; however, 131I-lipiodol therapy remains a feasible alternative for patients without a favourable response to other therapies, particularly for patients with Child-Pugh A liver cirrhosis.

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.

[Scintigraphically "hot" thyroid nodules mainly go hand in hand with a normal TSH]. / Szintigraphisch mehranreichernde Schilddrüsenknoten gehen überwiegend mit normwertigem TSH einher.

AIM: In recent years, various professional societies published guidelines for diagnostic evaluation of thyroid nodules, in which the indication for scintigraphy is restricted to patients with subnormal TSH values. It is seen controversial whether such recommendations should be transferred to Germany, partly because of lower iodine intake in this country and the consequent higher percentage of autonomous thyroid nodules, which are not accompanied by a measurable dysfunction. Since reliable data to this topic are scarce, we analyzed multicentrically the spectrum of scintigraphically "hot" and "warm" nodules under the current epidemiological conditions. PATIENTS, METHODS: In 10 German nuclear medicine out-patient institutions we evaluated the diagnostic data from a total of 514 patients, in whom unequivocally hyperfunctional nodules (focal increased uptake in comparison to perinodular tissue with a sonographically nodular correlative ≥1 cm) could be detected by (99m)Tc-pertechnetate scintigraphy. To minimize selection bias, the surveys were not carried out in hospitals.The recorded parameters included the thyroid hormone levels, the global (99m)Tc-uptake (TcTU), the size of each nodule and the total autonomous nodular volume (V(aut)). RESULTS: Only 20% of the patients with "hot" nodules had subnormal TSH levels (<0.1 to 0.33 mU / l), the remaining patients had TSH levels from 0.34 to 3.5 mU /l (in one third of the patients TSH levels even exceeded 1.0 mU/l). Moreover, we found no relevant correlation between TSH and TcTU or V(aut). CONCLUSIONS: In Germany, in at far the largest proportion of patients with autonomous thyroid nodules objectified by means of scintigraphy, TSH levels are within the normal range. Since such nodules with maximum safety can be classified as benign, a corresponding scintigraphic finding has a high priority for the patient. These current data support that it is not reasonable to restrict scintigraphy to patients with subnormal TSH values in this country.

Renal impairment after liver transplantation - a pilot trial of calcineurin inhibitor-free vs. calcineurin inhibitor sparing immunosuppression in patients with mildly impaired renal function after liver transplantation.

OBJECTIVES: Chronic kidney disease is frequent in patients after orthotopic liver transplantation (OLT) and has impact on survival. Patients receiving calcineurin inhibitors (CNI) are at increased risk to develop impaired renal function. Early CNI reduction and concomitant use of mycophenolat mofetil (MMF) has been shown to improve renal function. METHODS: The aim of this trial was to compare dose-reduced CNI/MMF versus CNI-free MMF/prednisone-based treatment in stable patients after OLT with respect to glomerular filtration rate (GFR). 21 patients (GFR 44.9 ' 9.9 mL/min/1.73m2 measured by 99m-Tc-DTPA-clearance, serum creatinine (SCr) 1.5 ' 0.42 mg/dL) were randomized either to exchange CNI for 10 mg prednisone (group 1; n = 8) or to receive CNI at 25% of the initial dose (group 2; n = 13) each in combination with 1000 mg MMF b.i.d. RESULTS: At month 12 mean SCr (-0.3 ' 0.4 mg/dL, p = 0.031) and GFR improved (8.6 ' 13.1 mL/min/ 1.73m superset2, p = 0.015) in group 2 but remained unchanged in group 1. Main side effects were gastroinstestinal symptoms (14.3%) and infections (4.8%). Two biopsy proven, steroid-responsive rejections occurred. In group 1 mean diastolic blood pressure (BP) increased by 11 ' 22 mmHg (p = 0.03). CONCLUSIONS: Reduced dose CNI in combination with MMF but not CNI-free-immunosuppression leads to improvement of GFR in patients with moderately elevated SCr levels after OLT. Addition of steroids resulted in increased diastolic blood pressure presumably counterbalancing the benefits of CNI withdrawal on renal function.

Beta-trace protein-based equations for calculation of GFR in renal transplant recipients.

Recently, we showed that serum beta-trace protein (BTP) is an alternative marker of glomerular filtration rate (GFR) in renal transplant recipients (RTR). We have now developed three BTP-based GFR formulae derived by multiple regression analyses from the patients who had participated in that study. Currently, we validated the diagnostic performance of these BTP-formulae in 102 consecutive RTR who underwent a technetium diethylenetriamine pentaacetic acid (DTPA) clearance for GFR measurement in comparison to the re-expressed Modification of Diet in Renal Disease (MDRD) equation and a recently proposed BTP-based equation (referred to as 'White equation'). The best-performing BTP formula was found to be: GFR = 89.85 x BTP(-0.5541)x urea(-0.3018). This equation estimated true GFR virtually without bias (+0.43 mL/min/1.73 m(2), not significant [NS]), while a small, but significant, overestimation was seen for the MDRD formula (+3.43 mL/min/1.73 m(2), p = 0.003). Precision and accuracies within 50% of true GFR (93.1% and 88.2%, respectively) tended to be higher for the BTP formula, but the differences did not reach significance. The White equation overestimated the true GFR by 9.43 mL/min/1.73 m(2)(p = 0.001), and was inferior with respect to precision and 50% accuracy (79.4%). BTP-based GFR calculations are reliable, and may serve as an alternative to the re-expressed MDRD equation.

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.

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.

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.

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.

Cystatin C-based calculation of glomerular filtration rate in kidney transplant recipients.

Cystatin C (Cys C) has been shown to be an alternative marker of renal function. However, estimation of the glomerular filtration rate (GFR) based on Cys C has received little attention. Recently, several Cys C-based equations were developed in different patient cohorts. To date, the benefit of a Cys C-based GFR calculation in patients after renal transplantation (RTx) remains to be elucidated. We compared the diagnostic accuracy of three Cys C-based formulae (Larsson, Hoek, Filler which used an immunonephelometric method) with the results of the Modification of Diet in Renal Disease (MDRD) formula. GFR was measured by means of technetium-diethylenetriamine pentaacetic acid ((99m)Tc-DTPA) clearance in 108 consecutive patients after RTx. Correlation coefficients of all calculated GFR estimates with the true GFR were high but did not differ significantly from one another (0.83-0.87). The MDRD and Filler equations overestimated GFR significantly, whereas the Larsson equation significantly underestimated GFR. Bias of the Hoek formula was negligible. Precision of the Hoek (8.9 ml/min/1.73 m(2)) and Larsson equations (9.6 ml/min/1.73 m(2)) were significantly better than MDRD equations (11.4 ml/min/1.73 m(2); P< or =0.035 each). Accuracy within 30% of real GFR was 67.0 and 65.1% for the MDRD and Filler formulae, and 77.1% for the Larsson and Hoek formulae, respectively. Accuracy within 50% of true GFR for the Hoek formula (97.2%) was better than for the MDRD equations (85.3%). Cys C-based formulae may provide a better diagnostic performance than creatinine-based equations in GFR calculation after RTx.

[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.

FDG-PET in immunocompetent patients with primary central nervous system lymphoma: correlation with MRI and clinical follow-up.

PURPOSE: The role of FDG-PET in primary central nervous system lymphoma (PCNSL) is unclear. It was the aim of this study to investigate the role of FDG-PET in detecting PCNSL and in predicting response to chemotherapy. METHODS: An FDG-PET scan of the brain was performed in 15 patients with histologically proven PCNSL (16 PET examinations, Siemens ECAT EXACT). PET was planned to investigate patients at the time of primary diagnosis, after chemotherapy and at the time of suspected relapse in seven, five and three cases, respectively. All except two patients simultaneously underwent MRI of the brain. FDG-PET results were correlated with histological results after stereotactic biopsy (primary diagnosis group) and with clinical data and MRI during follow-up. RESULTS: Six of the seven patients in the primary diagnosis group demonstrated a true positive finding (86%). In one of the true positive PET patients, there were two tumour lesions, one of which was only detectable on the FLAIR MRI sequence. In five patients, FDG-PET showed no sign of PCNSL during ongoing chemotherapy. These results were confirmed by the clinical follow-up (mean 26.6 months). MRI demonstrated minimal residual disease which had disappeared on further follow-up MRI in three of these five patients at the time of PET scanning. Recurrence of disease was confirmed concordantly by FDG-PET and MRI in three different patients. The standardised uptake value of all tumours was 10.2 (4.3-13.7). CONCLUSION: PCNSLs demonstrate high FDG uptake and can be diagnosed by FDG-PET with high sensitivity. It seems that FDG-PET is suitable for early therapeutic monitoring after chemotherapy.

Very early detection of response to imatinib mesylate therapy of gastrointestinal stromal tumours using 18fluoro-deoxyglucose-positron emission tomography.

AIM: To investigate whether 18F-FDG-PET allows early assessment of response to imatinib mesylate in GIST patients. PATIENTS AND METHODS: Five gastrointestinal stromal tumour (GIST) patients and one patient with a KIT-positive small cell cancer were studied. Treatment consisted of 400 mg imatinib mesylate daily. 18F-deoxyglucose-positron emission tomography (18F-FDG-PET) scans were done before and one week after starting imatinib mesylate therapy. RESULTS: Metabolic responses were detected after only one week of therapy in all GIST patients (four partial and one complete response). The mean decrease of the standardised uptake value was 60% (range 43 to 77%). In contrast, the tumour of the non-GIST patient was metabolically stable. Four of the 5 GIST patients achieved a partial response on CT after a mean duration of 23 weeks (range 6 to 48 weeks). CONCLUSION: 18F-FDG-PET is a valuable method for the detection of response to imatinib mesylate in patients with KIT-positive tumours as early as one week after starting therapy.

[Combined FDG PET/CT imaging for restaging of colorectal cancer patients: impact of image fusion on staging accuracy]. / PET-CT in der Nachsorge des kolorektalen Karzinoms: Einfluss der Bildfusion auf die Staginggenauigkeit.

PURPOSE: To evaluate the diagnostic impact of positron emission tomography (PET) with fluorine-18-labeled deoxy-D-glucose (FDG) combined with non-contrast computed tomography (CT) as PET-CT modality in restaging colorectal cancer patients. MATERIAL AND METHODS: In this retrospective study, 29 consecutive patients with histologically proven colorectal cancer (17 female, 12 male, aged 51-76 years) underwent whole body scans in one session on a dual modality PET-CT system (Siemens Biograph) 90 min. after i.v. administration of 370 MBq 18F-FDG. The CT imaging was performed with 40 mAs, 130 kV, slice-thickness 5 mm and without i.v. contrast administration. PET and CT images were reconstructed with a slice-thickness of 5 mm in coronal, sagittal and transverse planes. During a first step of analysis, PET and CT images were scored blinded and independently by a group of two nuclear medicine physicians and a group of two radiologists, respectively. For this purpose, a five-point-scale was used. The second step of data-analysis consisted of a consensus reading by both groups. During the consensus reading, first a virtual (meaning mental) fusion of PET and CT images and afterwards the "real" fusion (meaning coregistered) PET-CT images were also scored with the same scale. The imaging results were compared with histopathology findings and the course of disease during further follow-up. RESULTS: The total number of malignant lesions detected with the combined PET/CT were 86. For FDG-PET alone it was n = 68, and for CT alone n = 65. Comparing PET-CT and PET, concordance was found in 81 of 104 lesions. Discrepancies predominantly occurred in the lung, where PET alone often showed true positive results in lymph nodes and soft tissue masses, where CT often was false negative. Comparing mental fusion and "real" co-registered images, concordance was found in 94 of 104 lesions. In 13 lesions or, respectively, in 7 of 29 patients, a relevant information was gathered using fused images. CONCLUSION: Combined PET/CT leads to greater accuracy in the interpretation of data and is a valuable tool for diagnosis and anatomic localization of metastases in colorectal cancer patients.

Tc-99m labelled anti CD 66 antigranulocyte antibody imaging for assessment of bone marrow reserve.

Patients with metastatic disease to the bone marrow are at risk of significant hematologic toxicity, if they undergo myelotoxic chemotherapy. Tc-99m labelled Anti CD 66 monoclonal antibody imaging is a useful, noninvasive approach to the assessment of bone marrow reserve under such circumstances.

[Unspecific abdominal complaints: diagnosis with szintigraphy]. / Unklare Abdominalbeschwerden. Spezifische Diagnosestellung mittels Szintigraphie.

This case report describes a 65-year old man with symptomatic abdominal and pelvic splenosis. 50 Years ago he has had splenectomy after a road traffic accident. Ultrasound and CT revealed a bulky mass in the iliac fossa and multifocal intraabdominal nodules suggesting peritoneal carcinomatosis. Scintigraphy with Tc-99m-labelled heat damaged red blood cells led to definitive diagnosis. RBC-scintigraphy is a specific, easy performable diagnostic tool. It is cost-effective and can avoid other diagnostic procedures or explorative surgery.

[Therapy with radioisotopes in oncology. Palliative and curative approaches]. / Therapie mit Radioisotopen in der Onkologie. Palliative und kurative Ansätze.

For more than 50 years now, nuclear medicine has offered therapeutic procedures in oncology. These comprise bone pain palliation in bone metastases of prostate and breast cancer. For more than 20 years now, metaiodobenzylguanidine (mIBG) has been used to treat neuroendocrine tumors. Ten years ago, somatostatin analogues such as Y-90 Dotatoc became available for the treatment of somatostatin receptor-positive tumors. The intracavitary injection of radiocolloids has been well known for 5 decades now and can be used in malignant effusions. Invasive procedures such as intra-arterial injection of I-131 lipiodol may be applied in multifocal, nonresectable hepatocellular carcinoma. Beyond that, intratumoral injection of radioisotopes may be used in cutaneous metastases. Radioimmunotherapy using labeled tumor antibodies is now also available, especially in patients with non-Hodgkin's lymphoma.

[PET/CT imaging in head and neck tumors]. / PET-CT-Bildgebung bei Kopf-Hals-Tumoren.

AIM: To evaluate the usefulness of combined PET/CT examinations for detection of malignant tumors and their metastases in head and neck oncology. METHODS: 51 patients received whole body scans on a dual modality PET/CT system. CT was performed without i.v. contrast. The results were compared concerning the diagnostic impact of native CT scan on FDG-PET images and the additional value of fused imaging. RESULTS: From 153 lesions were 97 classified as malignant on CT and 136 on FDG/PET images, as suspicious for malignancy in 33 on CT and 7 on FDG-PET and as benign in 23 on CT and 10 on FDG-PET. With combined PET/CT all primary and recurrent tumors could be found, the detection rate in patients with unknown primary tumors was 45%. Compared to PET or CT alone the sensitivity, specifity and accuracy could be significantly improved by means of combined PET/CT. CONCLUSION: Fused PET/CT imaging with [F18]-FDG and native CT-scanning enables accurate diagnosis in 93% of lesions and 90% of patients with head and neck oncology.