Rainer Görges

FDG-PET/CT in re-staging of patients with lymphoma

The aim of this study was to evaluate the clinical significance of combined fluorine-18 fluorodeoxyglucose positron emission tomography and computed tomography (FDG-PET/CT) in patients with lymphoma, and to compare the FDG-PET/CT staging results with those of FDG-PET and CT alone. Twenty-seven patients were studied. Each patient had clinical follow-up for >12 months and entered complete follow-up evaluation. Patient-based evaluation showed a sensitivity of 78% for CT alone, 86% for FDG-PET alone, 93% for CT and FDG-PET read side by side, and 93% for combined FDG-PET/CT imaging. Region-based evaluation showed a sensitivity for regional lymph node involvement of 61%, 78%, 91% and 96% respectively. FDG-PET/CT imaging is superior to CT alone (P=0.02) and has additional benefit over FDG-PET alone due to exact anatomical localisation. We conclude that FDG-PET/CT imaging is accurate in re-staging lymphoma and offers advantages over separate FDG-PET and CT imaging.

Preoperative Diagnostic Value of [18F] Fluorodeoxyglucose Positron Emission Tomography in Patients With Radioiodine-Negative Recurrent Well-Differentiated Thyroid Carcinoma

ObjectiveTo assess the utility of 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) to detect recurrent disease in the follow-up of patients with well-differentiated thyroid cancer (WDTC) who have negative diagnostic 131I scans and abnormal thyroglobulin levels. Summary Background DataIn general, patients with WDTC have an excellent long-term prognosis when appropriate surgical treatment and follow-up are carried out. After total thyroid ablation, whole-body 131I scintigraphy and measurement of serum thyroglobulin are useful diagnostic tools to detect persistent or recurrent malignancy. In case of tumor dedifferentiation, decreased or lost iodine-accumulating ability may lead to false-negative 131I scanning results. The diagnostic and therapeutic delay is responsible for a poor prognosis in this subgroup of patients. Efforts have been made in the search for suitable imaging modalities capable of early detection of recurrent thyroid carcinoma. MethodsThe authors prospectively analyzed 24 patients with WDTC, negative results of whole-body 131I scintigraphy, and elevated serum thyroglobulin concentrations. Attenuation-corrected whole-body FDG-PET scans from the neck to the upper legs were performed. In addition, all patients underwent cervical ultrasonography. The results of the imaging studies were compared with histopathologic findings. If no resection of the suspicious lesion was carried out, computed tomography data were used as control criteria. ResultsOverall, FDG-PET disclosed 38 hot spots. The sensitivity of the method was 94.6%, but the specificity was lower (25.0%). The diagnostic accuracy was 87.8%. There were three false-positive results in two patients with benign cervical lymph nodes. In one patient with regional lymph node metastases in the neck, two false-negative results were obtained. Ultrasound classified both findings as malignant, however. Because of unexpected findings, FDG-PET suggested potential modification of the surgical management in nine patients. Distant metastases could be disclosed using FDG-PET in only three patients. ConclusionsFDG-PET is a useful diagnostic tool in the follow-up of thyroidectomized patients with WDTC, negative 131I scanning results, and abnormal serum thyroglobulin concentrations. The method detects metastatic disease in 94.6% of cases. PET results changed surgical tactics in a significant number of patients. Accurate staging of locoregional cancer recurrence in the neck may be consummately obtained by concomitant analysis of PET and ultrasound results.

The value of fluorine-18 fluorodeoxyglucose PET in patients with medullary thyroid cancer

Abstract.The early detection of metastases from medullary thyroid cancer (MTC) is important because the only curative therapy consists in surgical removal of all tumour tissue. There is no single sensitive diagnostic imaging modality for the localization of all metastases in patients with MTC. Therefore, in many cases several imaging modalities (e.g. ultrasonography, magnetic resonance imaging, computerized tomography and scintigraphy using pentavalent technetium-99m dimercaptosuccinic acid, thallium-201 chloride, indium-111 pentetreotide, anti-CEA antibodies or metaiodobenzylguanidine) must be performed consecutively in patients with elevated calcitonin levels until the tumour is localized. In this prospective study, we investigated the value of fluorine-18 fluorodeoxyglucose positron emission tomography ([18F]FDG PET) in the follow-up of patients with MTC. [18F]FDG PET examinations of the neck and the chest were performed in 20 patients with elevated calcitonin levels or sonographic abnormalities in the neck. Positive [18F]FDG findings were validated by histology, computerized tomography or selective venous catheterization. [18F]FDG PET detected tumour in 13/17 patients (nine cases were validated by histology, four by computerized tomography). Five patients showed completely negative PET scans (of these cases, one was true-negative and four false-negative). One patient with [18F]FDG accumulation in pulmonary lesions from silicosis and one patient with a neck lesion that was not subjected to histological validation had to be excluded. Considering all validated localizations, [18F]FDG PET detected 12/14 tumour manifestations in the neck, 6/7 mediastinal metastases, 2/2 pulmonary metastases and 2/2 bone metastases. In two patients with elevated calcitonin levels, no diagnostic modality was able to localize a tumour. The sensitivity of [18F]FDG PET in the follow-up of MTC was 76% (95% confidence interval 53%–94%); this is encouraging. [18F]FDG PET promises to be a valuable diagnostic method, especially for the detection of lymph node metastases, surgical resection of which can result in complete remission.

Health-related quality of life, depression and anxiety in thyroid cancer patients

Objectives: We examined the relationships among physical complaints, health-related quality of life (HRQL), anxiety and depression in differentiated thyroid cancer (DTC) patients under short-term hypothyroidism. Methods: We conducted a cross-sectional study in 136 patients hypothyroid on thyroid hormone withdrawal (THW) hospitalized for radioiodine administration. Patients were assessed using Short Form SF-36 (SF-36), Hospital Anxiety and Depression Scale (HADS), Profile of Mood States (POMS), Beck Depression Inventory (BDI), and physical complaints. Results: Compared to the German general population, hypothyroid patients had significantly impaired HRQL. Surprisingly, the prevalence of anxiety (62.5%), but not depression (17.9%) was much higher in hypothyroid DTC patients than in the general population. In multivariate analysis, depression and age were independently associated with the physical health score (R2 = 0.21), but only psychological variables (depression, mood disturbance, and anxiety) were associated with the mental health score (R2 = 0.43), on the SF-36 HRQL instrument. Conclusions: HRQL is severely impaired in DTC patients under short-term hypothyroidism. As potential predictors of generic HRQL impairment, depression, anxiety, and mood disturbance could be used to preselect the patients most needing psychiatric care. The high frequency of anxiety should be considered in the aftercare of thyroid cancer patients.

Radionuclide-labeled somatostatin analogues for diagnostic and therapeutic purposes in nonmedullary thyroid cancer.

Despite the fact that several recent studies report an expression of somatostatin receptors in nonmedullary thyroid cancer (non-MTC), there is still no consensus concerning the diagnostic and therapeutic usefulness of radionuclide-labeled somatostatin analogues in non-MTC. We present the results of 50 scintigraphic studies with (111)In-Pentetreotide ((111)In-P) in 48 patients with metastasizing non-MTC (n = 9 papillary, n = 9 follicular, n = 29 Hurthle cell, n = 1 insular carcinoma). The findings were compared with histology and with other imaging modalities. (111)In-P provided unequivocally positive results in 37 of 50 (74%) of the patients (27% in the 11 patients with current thyroglobulin levels <10 ng/mL and 85% in the patients with thyroglobulin >10 ng/mL). Histopathology demonstrated that maximal uptake was observed in Hurthle cell carcinoma (95% positive examinations if thyroglobulin exceeds 10 ng/mL). We also describe for the first time dosimetric and clinical data from the courses of 90Y-DOTATOC therapy in three patients with progressive, somatostatin-receptor-positive non-MTC (up to 9.3 GBq per 4 cycles). Tumor progression could not be stopped in any of the patients treated with 90Y-DOTATOC. We conclude that (111)In-P is a promising tool for whole-body diagnosis in nonradioiodine-accumulating non-MTC, especially in Hürthle cell cancer, and if 2-[18F]fluorodeoxyglucose-positron emission tomography (FDG-PET) is not available. Although the number of patients treated with 90Y-DOTATOC is still limited, our applied treatment protocol appears to be ineffective in metastasizing non-MTC.

Relationship between cumulative radiation dose and salivary gland uptake associated with radioiodine therapy of thyroid cancer.

AimTo estimate the individual absorbed dose to the parotid and submandibular salivary glands in radioiodine therapy and its dependence from the previous cumulative therapy. MethodsFifty-five patients with differentiated thyroid carcinoma after thyroidectomy received 1–21 GBq 131I using single activities of 1–6 GBq. The patients were stratified according to the cumulative activities into low-activity (1–2 GBq), middle-activity (3–7 GBq), and high-activity groups (9–21 GBq). The time–activity curves over the respective salivary glands were derived from multiple static calibrated images measured for each patient up to 48 h after ingestion of the radioiodine therapy capsule with a gamma camera. Manually drawn regions of interests were used to determine the background activities and the activities arising from the salivary glands. The gland volumes were determined by ultrasonography using appropriate volume models. ResultsThe median absorbed dose per administered activity of each single parotid and submandibular gland was about 0.15 Gy·GBq−1 (range, 0.1–0.3 Gy·GBq−1) and 0.48 Gy·GBq−1 (range, 0.2–1.2 Gy·GBq−1), respectively. The maximum uptake of both gland types was significantly lower for the high-activity than for the low-activity groups and correlated with the mean cumulative administered activity of the activity groups. ConclusionThe iodine uptake of salivary glands is significantly reduced, whereas the absorbed dose per administered 131I activity was not significantly decreased during the course of therapy. Comparing the well-known dose–effect relationships in external radiation therapy, the absorbed dose per administered 131I activity is too low to induce comparable radiation damage, suggesting an inhomogeneous distribution of 131I in human salivary glands.

The C allele of the GNB3 C825T polymorphism of the G protein β3-subunit is associated with an increased risk for the development of oncocytic thyroid tumours

Carriers of the C allele of the common C825T polymorphism in the GNB3 gene of the G protein have been associated with the development of follicular thyroid adenomas. Since the C allele of this polymorphism is related to a lower signalling capacity, it was speculated whether the C825T polymorphism may play a particular role in oncocytic thyroid tumours, which are recognized for their reduced ability to synthesize thyroid‐specific proteins and hormones, although they possess an intact thyroid‐stimulating hormone receptor–adenylyl cyclase system. Using pyrosequencing, both the genotype distribution and the allele frequency of the C825T polymorphism were investigated in a series of 104 patients with oncocytic thyroid tumours of follicular cell origin [58 adenomas, 41 follicular thyroid carcinomas (FTCs), and five papillary thyroid carcinomas (PTCs)]; the results were compared with those obtained from 321 age and gender‐matched healthy blood donors and a series of 327 non‐oncocytic thyroid tumours of follicular cell origin (119 adenomas, 80 FTCs, and 186 PTCs). Analysis of the genotype distribution (comparing oncocytic with non‐oncocytic tumours of the present series) revealed a significantly increased odds ratio (OR) for CC versus TT (OR = 4.22; p = 0.011) and CC versus CT (OR = 1.62; p = 0.049) carriers to develop an oncocytic thyroid tumour; ORs to develop an oncocytic thyroid tumour were also increased comparing the genotype distribution between the group of oncocytic tumours and healthy controls for CC versus TT (OR = 3.73; p = 0.017) and CC versus all T carriers (OR = 1.56; p = 0.034). Oncocytic thyroid tumours as a group showed a statistically significant increase of the C‐allele frequency when compared with all non‐oncocytic tumours (p = 0.0039) as well as healthy blood donors (p = 0.017). The results strongly suggest that the C allele of the GNB3 C825T polymorphism of the G protein β3‐subunit is associated with an increased risk for the development of oncocytic thyroid tumours. This polymorphism may thus be considered a (co)factor favouring the development of oncocytic thyroid tumours, although the biological mechanism(s) underlying this association remain obscure. Copyright

Different genotype distribution of the GNB3 C825T polymorphism of the G protein β3 subunit in adenomas and differentiated thyroid carcinomas of follicular cell origin

A C825T polymorphism has been demonstrated in the GNB3 gene that encodes the Gβ3 subunit of heterotrimeric G proteins. Due to enhanced G protein activation, the GNB3 825T allele is associated with an increased signal transduction activity. To elucidate a possible role in the development and course of thyroid tumours of follicular cell origin, C825T polymorphism genotypes and allele frequencies were investigated in a series of adenomas and differentiated carcinomas. Genotypes and the allele frequency of the Gβ3 polymorphism were investigated in samples from 361 patients (all white Caucasians) with differentiated thyroid tumours of follicular cell origin [80 adenomas and 95 follicular (FTCs) and 186 papillary carcinomas (PTCs)]. The results were compared with those of 1859 healthy controls. Both the genotype distribution (p = 0.029) and the allele frequency (p = 0.028) of the adenoma group were statistically significantly different from those of the control group. Thyroid adenomas also differed for both parameters significantly from FTCs (p = 0.042 and 0.033, respectively) and PTCs (0.0018 and 0.0081, respectively), whereas no statistical difference was noted between the FTC and PTC groups. Although the biological significance of these observations remains obscure, the results are suggestive of a putative role for the GNB3 polymorphism in thyroid tumour development and/or progression. Further research has to elucidate if, and to what extent, this common germ‐line variation influences the TSH‐triggered signalling pathways responsible for thyroid function and proliferation. Copyright

Optimizing preoperative imaging in primary hyperparathyroidism

BackgroundScintigraphy of the hyperfunctioning parathyroid glands using technetium 99m (99mTc)-methoxyisobutylisonitrile (99mTc-MIBI) is an established and highly sensitive preoperative localization tool whose importance has been further increased by advances in minimally invasive surgery .The goal of the present prospective study was to determine the benefit of optimized imaging in a consistent patient population.MethodsEighty-four patients with first presentations of primary hyperparathyroidism were investigated with 99mTc-MIBI scintigraphy, thyroid scintigraphy, and cervical ultrasonography. The evaluation algorithm consisted of (a) evaluation of the planar images alone, (b) additional evaluation of single-photon emission computed tomography (SPECT), (c) additional evaluation of thyroid gland scintigraphy, and (d) additional evaluation of ultrasound. All patients subsequently underwent parathyroidectomy. The intraoperative and the histologic findings were correlated with the results of the scintigraphic imaging.ResultsThe sensitivity of planar parathyroid scintigraphy was 74% and could be increased to 91% by the additional investigations. The difference was statistically significant (p<0.05). At the same time, a small increase in specificity from 96% to 99% was seen.ConclusionsPrior to minimally invasive treatment of hyperparathyroidism, we recommend combined localization studies consisting of sequential 99mTc-MIBI scintigraphy, additional SPECT plus thyroid gland scintigraphy, plus high-resolution cervical ultrasonography.

Pathologie des Schilddrüsenkarzinoms

ZusammenfassungSchilddrüsenkarzinome machen etwa 1% aller menschlichen Malignome aus und stellen somit einen eher seltenen Tumortyp dar. Sowohl die Abgrenzung der Karzinome von gutartigen Läsionen (Hyperplasien, Adenome) als auch die für die weitere Therapie notwendige exakte Klassifizierung der Schilddrüsenkarzinome stellen in der täglichen Routinepathologie mitunter eine diagnostische Herausforderung dar. Schilddrüsenkarzinome mit Follikelzellursprung werden nunmehr auch in der kürzlich erschienenen WHO-Klassifikation der Schilddrüsentumoren aufgrund ihres biologischen Verhaltens in papilläre, follikuläre, gering differenzierte und anaplastische Karzinome unterteilt. Während die differenzierten Karzinome (papilläre und follikuläre Karzinome) ganz überwiegend eine hervorragende Prognose aufweisen, zeigt das gering differenzierte Karzinom eine deutlich schlechtere und das anaplastische Karzinom in der Regel eine infauste Prognose. Das von den C-Zellen ausgehende medulläre Karzinom tritt in einer sporadischen und familiären Form auf. Das familiäre medulläre Karzinom wird autosomal-dominant vererbt und kann heute in fast allen Fällen durch entsprechende Mutationen des RET-Protoonkogens nachgewiesen werden.AbstractThyroid carcinoma accounts for approximately 1% of all human malignancies and is thus a rather rare tumour. Both its differential diagnosis from benign lesions (thyroid hyperplasia and adenoma) and exact classification may cause substantial difficulties in daily routine diagnostic pathology. Due to their different biological behaviour the recently published WHO classification of thyroid tumours subdivides thyroid carcinomas of follicular cell origin into well-differentiated carcinomas (papillary and follicular carcinoma), poorly differentiated carcinomas and anaplastic carcinomas. Whereas papillary and follicular carcinomas are usually associated with good prognosis, poorly differentiated carcinoma shows a significantly less favourable and anaplastic carcinoma even a devastating outcome. Thyroid medullary carcinoma, originating from calcitonin-producing C cells, occurs in a sporadic and familial form; the familial type is inherited in an autosomal dominant manner and shows specific germ line mutations of the RET proto-oncogene.