Karl H. Bohuslavizki

Value of FDG PET in patients with fever of unknown origin.

Fever of unknown origin (FUO) is a diagnostic challenge, because the cause of such fever may be manifold. Studies on the use of positron emission tomography (PET) using 18F-fluorodeoxyglucose (18F-FDG), for the diagnosis of inflammation in patients with osteomyelitis or HIV have been promising and suggest its use in patients with FUO. In this study, we used FDG PET in 16 patients with FUO in whom conventional diagnostics had not been conclusive. In 12 patients, (75%) non-physiological accumulations of FDG were found which led to the final diagnosis in 11 patients (69%). FDG PET was negative in four patients (25%). Two of these patients had rheumatic fever, while in the other two patients the origin of fever could not be detected within 3 months after PET by any other laboratory or imaging means. These findings point to the high sensitivity of FDG whole-body PET for the detection of morphologically assessable foci as an origin of FUO. Moreover, they suggest a high negative predictive value of FDG PET in the setting of FUO, since in no patient with a negative FDG PET could a morphological origin of the fever be determined. In conclusion, FDG whole-body PET appears to be a promising diagnostic tool in patients with FUO, in whom conventional diagnostics had been unsuccessful.

Comparison of fluorodeoxyglucose positron emission tomography and "conventional diagnostic procedures" for the detection of distant metastases in breast cancer patients.

The presence of distant metastases is the main prognostic factor in patients with breast cancer and has a significant influence in the choice of therapy. Therefore, chest X-ray, bone scintigraphy and ultrasound of the abdomen are performed to detect distant metastases at diagnosis and follow-up. Fluorodeoxyglucose positron emission tomography (FDG PET) has been shown to provide sensitive detection of primary tumour and metastases for many tumour entities, but little information is available about the diagnostic value for breast cancer patients. This study retrospectively compared FDG PET for detection of metastatic disease with chest X-ray, bone scintigraphy and ultrasound of the abdomen, referred to as ‘conventional diagnostic procedures’ (CDPs), in 50 breast cancer patients. Imaging procedures were analysed in a blinded fashion with the results classified as ‘no evidence of metastases’, ‘equivocal’ and ‘evidence of metastases’. Clinical follow-up and the results of other imaging modalities including computed tomography and magnetic resonance imaging were used to determine if metastases were present. FDG PET identified metastatic disease with a sensitivity and specificity of 86% and 90% as compared to 36% and 95% for CDPs, respectively. Regarding ‘equivocal’ and ‘evidence of metastases’ as positive, the sensitivity of CDPs increased to 57% with a corresponding specificity of 81%, whereas sensitivity and specificity of FDG PET remained unchanged. Regarding different localities of metastases the sensitivity of FDG PET was superior in the detection of pulmonary metastases and especially of lymph node metastases of the mediastinum in comparison to chest X-ray, whereas the sensitivity of FDG PET in the detection of bone and liver metastases was of the same magnitude as compared with bone scintigraphy and ultrasound of the abdomen.

Salivary gland protection by amifostine in high-dose radioiodine treatment: results of a double-blind placebo-controlled study.

PURPOSE Salivary gland impairment is a well-recognized side effect following high-dose radioiodine treatment (HD-RIT). Since differentiated thyroid cancer has a good prognosis, reduction of long-term side effects is important. Therefore, the effect of amifostine was studied in HD-RIT. PATIENTS AND METHODS Parenchymal function was assessed by quantitative salivary gland scintigraphy performed prospectively in 50 patients with differentiated thyroid cancer before and 3 months after HD-RIT with either 3 GBq iodine ((131)I) (n=21) or 6 GBq (131)I (n=29) in a double-blind, placebo-controlled study. Twenty-five patients were treated with 500 mg/m2 amifostine intravenously before HD-RIT and 25 patients served as controls, who received physiologic saline solution. Xerostomia was graded according to World Health Organization (WHO) criteria. RESULTS Before HD-RIT in 25 control patients, uptake of technetium-99m (99mTc)-pertechnetate was 0.45%+/-0.16% and 0.42%+/-0.16% in parotid and submandibular glands, respectively. Three months after HD-RIT, parenchymal function was significantly (P < .001) reduced by 40.2%+/-14.1% and 39.9%+/-15.3% in parotid and submandibular glands, respectively. Nine control patients developed grade I and two grade II xerostomia. In 25 amifostine-treated patients, uptake of 99mTc-pertechnetate was 0.46%+/-0.16% and 0.43%+/-0.17% in parotid and submandibular glands, respectively. Three months after HD-RIT, parenchymal function of salivary glands was not significantly altered (P=.691) and xerostomia did not occur in any of these patients. CONCLUSION Parenchymal damage in salivary glands caused by HD-RIT can significantly be reduced by amifostine, which may improve the quality of life of patients with differentiated thyroid cancer.

Quantitative salivary gland scintigraphy in the diagnosis of parenchymal damage after treatment with radioiodine

SummaryThis study was undertaken to quantify salivary gland parenchymal damage after radioiodine treatment with a standard protective regimen of ascorbic acid. Altogether, 106 patients underwent quantitative salivary gland scintigraphy with 99Tcm-pertechnetate prior to and 3 months after radioiodine therapy. Parenchymal function was quantified by calculating 99Tcm-pertechnetate uptake 13 min post-injection. Patients received 131I doses ranging from 400 MBq to 24 GBq (cumulative). Among the patients who received large doses of 131I, severe parenchymal destruction could be visually analysed as well as quantitatively evaluated. In contrast, after low-dose radioiodine treatment, mild parenchymal impairment was demonstrated by quantitative evaluation only. In conclusion, standardized quantitative salivary gland scintigraphy is essential for the reliable detection of mild parenchymal malfunction. Despite the standard protection regimen using ascorbic acid as a sialogogue, radioiodine therapy induces loss of salivary gland parenchymal function even with low doses of 131I.

Salivary gland protection by amifostine in high-dose radioiodine therapy of differentiated thyroid cancer

BackgroundSalivary gland impairment following high-dose radioiodine treatment is a well-recognized side effect, in general caused by free radicals. Therefore, it seemed promising to evaluate the radioprotective effect of the radical scavenger amifostine in patients receiving high-dose radioiodine therapy.Patients and MethodQuantitative salivary gland scintigraphy using 100 to 120 MBq Tc-99m-pertechnetate was performed in 17 patients with differentiated thyroid cancer prior to and 3 months after radioiodine treatment with 6 GBq 1–131. Eight patients were treated with 500 mg/m2 amifostine prior to high-dose radioiodine treatment and compared retrospectiveley with 9 control patients. Xerostomia was graded according to WHO criteria.ResultsIn 9 control patients high-dose radioiodine treatment significantly (p < 0.01) reduced Tc-99m-pertechnetate uptake by 35.4 ±22.0% and 31.7 ±21.1% in parotid and submandibular glands, respectively. Of these 9 patients, 3 exhibited xerostomia Grade I (WHO). In contrast, in 8 amifostine-treated patients, there was no significant (p = 0.878) decrease in parenchymal function following high-dose radioiodine treatment, and xerostomia did not occur in any of them.ConclusionParenchymal damage in salivary glands induced by high-dose radioiodine treatment can be reduced significantly by amifostine. This may help to increase patients’ quality of life in differentiated thyroid cancer.ZusammenfassungHintergrundEine SchÄdigung der Speicheldrüsen mit konsekutiver Xerostomie ist eine bekannte, durch freie Radikale verursachte Nebenwirkung der hochdosierten Radiojodtherapie bei Patienten mit differenziertem Schilddrüsenkarzinom. Daher wurde der Effekt des RadikalfÄngers Amifostin nach hochdosierter Radiojodtherapie geprüft.Patienten und MethodeIm Rahmen eines Heilversuchs wurde eine limitierte Anzahl von Patienten untersucht. Vor und drei Monate nach Gabe von 6 GBq 1–131 wurde eine quantitative Speicheldrüsenszintigraphie mit 100 bis 120 MBq Tc-99m-Pertechnetat an 17 Patienten mit differenzierten Schilddrüsenkarzinomen durchgeführt. Acht Patienten erhielten vor Radiojodtherapie 500 mg/m2 Amifostin und wurden mit einer historischen Kontrollgruppe aus neun Patienten verglichen. Eine Xerostomie wurde nach WHO-Kriterien beurteilt.ErgebnisseDie Patienten der Kontrollgruppe wiesen sowohl für die Glandulae parotides als auch für die Glandulae submandibulares eine signifikante Verminderung der Tc-99m-Pertechnetat-Aufnahme um 35,4 ±22,0% bzw. 31,7 +21, 1% (Abbildungen 1 und 2, Tabellen 1 und 2) als Zeichen einer ParenchymschÄdigung auf. Bei drei dieser neun Patienten fand sich eine Xerostomie Grad I (WHO). Im Gegensatz dazu konnte bei den mit Amifostin behandelten Patienten keine signifikante Verminderung der Parenchymfunktion festgestellt werden (p = 0,878). Dementsprechend wies keiner dieser Patienten eine Xerostomie auf.SchluΒfolgerungBei Patienten mit differenziertem Schilddrüsenkarzinom kann die durch hochdosierte Radiojodtherapie regelhaft verursachte ParenchymschÄdigung der Speicheldrüsen signifikant vermindert werden. Dies könnte die LebensqualitÄt dieser Patienten wesentlich verbessern.

Long-term results of radiation synovectomy: a clinical follow-up study.

Radiation synovectomy by intra-articular injection of β-emitting radionuclides is a reliable and easy-to-perform therapy without harmful side effects for the treatment of inflammatory rheumatoid as well as degenerative joint diseases. The indication for radiation synovectomy is based on both clinical symptoms and on proven hyperperfusion, with active synovitis being seen on a pre-therapeutic three-phase bone scan. In this study, the clinical response after 6-18 months, evaluated by a standardized questionnaire, was compared with the reduction of synovitis seen on three-phase bone scintigraphy after treatment of 475 joints in 151 patients. The best clinical results were obtained in cases of true rheumatoid arthritis (73.4%), with less in other kinds of arthritis (48.8%) such as psoriatic or reactive arthritis. Because of the inflamed synovium being the main target tissue, clinical results in osteoarthritis with severe bone destruction are poorer (33.9%). However, synovitis can be markedly reduced (in approximately 70%), regardless of the underlying diagnosis, as shown by post-therapeutic three-phase bone scanning. Radiation synovectomy can be recommended in all kinds of arthritis. It should also be considered in cases of osteoarthritis as a last therapeutic option prior to joint replacement.

Somatostatin receptor scintigraphy in the differential diagnosis of meningioma.

The aim of this study was to evaluate somatostatin receptor scintigraphy (SRS) in patients with meningioma proven or suspected on magnetic resonance imaging (MRI). Prior to surgery, 47 patients were investigated up to 24 h following the injection of 200 MBq 111In-octreotide. Tracer uptake was compared with the histological presence of meningioma. Histology revealed 43 meningiomas, 3 neurinomas and 1 ependymoma. A true-positive SRS result was obtained in 36 patients, in 13 of whom a tumour volume of < 10 ml was noted. A false-negative SRS result was obtained in seven patients, all of whom had a tumour volume of < 10 ml. Whereas MRI alone was decisive in 38 of 47 patients, it could only provide a differential diagnosis in the remaining 9 patients. A positive SRS result confirmed meningioma in five of these patients, and a negative SRS result excluded meningioma in the other four. Therefore, cases of SRS-negative meningioma do exist. Nevertheless, significant clinical benefit can be obtained from functional imaging with 111In-octreotide in patients with an inconclusive MRI result, as large meningiomas can be excluded by scintigraphy alone, whereas meningiomas of any size may be confirmed in combination with specific MRI results.

Radiotherapy with iodine-131 in recurrent malignant struma ovarii

Malignant struma ovarii is a very rare disease and, therefore, there is neither common agreement on treatment regimens nor sufficient follow-up experience. We present a case of a 49-year-old woman with malignant struma ovarii of the follicular type, who received ablative radioiodine treatment after thyroidectomy and surgical removal of the primary tumour. During followup examinations an increasing thyroglobulin level was found, caused by a tumour relapse with suspected urinary bladder infiltration on CT and proven uptake of radioiodine on whole-body scanning with iodine-131. After administration of 6 GBq131I, complete tumour regression was achieved with no evidence of a new relapse during a 30-month follow-up period. Correspondingly, repeated thyroglobulin measurements were all negative. This case demonstrates the benefit of combined surgical and radioiodine treatment of malignant struma ovarii for both monitoring and therapy of relapse or metastases; thus, the same therapeutic regimen as is employed in primary differentiated thyroid carcinoma may be recommended.

Lymphoscintigraphy in tumors of the head and neck using double tracer technique.

UNLABELLED Knowledge of possible lymphatic drainage may facilitate planning of surgery for patients with head and neck tumors. Therefore, the aim of this study was to present a method of lymphoscintigraphy with special attention to an accurate correlation of lymphatic drainage to anatomic regions. METHODS Lymphoscintigraphy was performed using a double tracer technique before surgery in a total of 75 patients with squamous cell carcinoma of the head and neck. All patients received 100 MBq 99mTc-colloid at three to four peritumoral sites. A perchlorate solution (2 mL) was given orally to block salivary glands and the thyroid gland. Patients received 50 MBq 99mTc-pertechnetate intravenously for body contouring 20 min postinjection. Planar images were obtained over 5 min each, at 30 min and 4 h postinjection from anterior, right lateral and left lateral views with a large-field-of-view gamma camera. Lymphatic drainage was assessed by visual inspection and assigned to six cervical compartments. RESULTS Neither the salivary glands nor the thyroid gland were seen in any of the patients. In 22 of 75 patients (29.3%), the injection site was the only focal tracer uptake seen. In contrast, lymphatic drainage was identified in the remaining 53 patients (70.7%), and lymph nodes could be assigned easily to the six cervical compartments. Of 75 patients, 36 (48%) exhibited ipsilateral lymphatic drainage. In addition, 17 patients (22.7%) with unilateral tumor showed bilateral (n = 12), contralateral (n = 2) or retropharyngeal (n = 3) lymphatic drainage. In 3 of these 17 patients, bilateral lymph node metastases were proven. A subgroup of 12 patients (16%) exhibited N2c nodal status, despite a unilateral localized primary tumor. In 3 of these 12 patients, surgery was extended as a result of scintigraphic findings from unilateral toward bilateral neck dissection, and histology confirmed nodal involvement in these patients. CONCLUSION Lymphoscintigraphy using the double tracer technique allows an accurate correlation of lymphatic drainage to the six cervical compartments. This may provide the basis for a re-evaluation of its impact in treatment planning of patients with head and neck tumors.

Radioprotection of salivary glands by S-2-(3-aminopropylamino)-ethylphosphorothioic (amifostine) obtained in a rabbit animal model

BACKGROUND Impairment of salivary gland function following high-dose radioiodine treatment (HDRIT) is a well-recognized side effect of the treatment. Because differentiated thyroid cancer has an excellent prognosis, reduction of long-term side-effects is mandatory. Therefore, the aim of this study was to investigate the radioprotective effect of amifostine in a rabbit animal model. METHODS Salivary gland scintigraphy was performed in a total of 16 New Zealand White rabbits. Uptake of 99-Tc-pertechnetate was calculated in percentage of injected activity as a quantitative measure of both salivary gland and thyroid function. Reproducibility of salivary gland scintigraphy was evaluated in one rabbit without any intervention. Fifteen rabbits were studied prior to and up to 6 months after high-dose radioiodine treatment applying 2 GBq 131I. Ten animals received 200 mg/kg amifostine prior to high-dose radioiodine therapy, and 5 served as controls. Salivary glands were examined histopathologically. RESULTS Variation coefficient of parenchymal function was less than 3.8% in salivary glands. Prior to HDRIT, thyroid uptake was 0.417+/-0.373% and 0.421+/-0.241% in control and amifostine-treated rabbits, respectively. Four weeks after HDRIT, complete ablation of the thyroid was achieved in both groups. Prior to HDRIT, uptake of 99mTc-pertechnetate in salivary glands of five control rabbits was not significantly different from ten amifostine-treated rabbits. In control rabbits 6 months after HDRIT, parenchymal function was reduced significantly (p < 0.0001) by 75.3+/-5.3% and 53.6+/-17.4% in parotid and submandibular glands, respectively. In contrast, in amifostine-treated rabbits, parenchymal function was reduced by 10.6+/-3.4% and 6.5+/-4.3% (p > 0.05) in parotid and submandibular glands, respectively. Histopathologically, marked lipomatosis was observed in control animals but was negligible in amifostine-treated animals. CONCLUSION Parenchymal damage in salivary glands induced by high-dose radioiodine treatment can be significantly reduced by amifostine in this rabbit animal model. This corresponds to data obtained in patients with differentiated thyroid cancer.