Impact of surgical resection extension on outcome for primary well-differentiated thyroid cancer-a retrospective analysis.

BACKGROUND: The surgical resection extension in well-differentiated thyroid cancer is controversially discussed with the possibility of an overtreatment on the one hand against the risk of local disease recurrence. The aim of this study is to evaluate how the surgical resection extension with the adjunction of radioiodine therapy affects postoperative morbidity and the oncologic outcome of patients primarily treated for well-differentiated thyroid cancer. METHODS: All patients undergoing primary surgery for a well-differentiated, non-recurrent thyroid cancer from January 2005 to April 2013 at Tuebingen University Hospital were retrospectively analyzed. RESULTS: Papillary thyroid cancer (PTC) was present in 73 patients (including 27 papillary microcarinoma) and follicular thyroid cancer in 14 patients. Fifty-six of 87 patients (64%) underwent one-stage surgery, of which 26 patients (30%) received simultaneous lymph node dissection (LND). The remaining 31 patients (36%) underwent a two-stage completion surgery (29 patients with LND). Only in three patients a single lymph node metastasis was newly detected during two-stage completion surgery. Patients with LND at either one-stage and two-stage completion surgery had a significant higher rate of transient postoperative hypocalcemia. Postoperative adjuvant radioiodine therapy was performed in 68 of 87 patients (78%). After a median follow-up of 69 months [range 9-104], one local recurrence was documented in a patient suffering from PTC 23 months after surgery. CONCLUSION: No prophylactic two-stage lymphadenectomy should be performed in case of well-differentiated thyroid cancer to avoid unnecessary complication without any proven oncologic benefit.

Hypothyroidism during second-line treatment of multidrug-resistant tuberculosis: a prospective study.

SETTING: Hypothyroidism is an adverse effect of certain anti-tuberculosis drugs. DESIGN: This is a prospective study of the frequency and possible pathomechanisms associated with hypothyroidism due to second-line treatment of multidrug-resistant tuberculosis. Fifty human immunodeficiency virus negative patients and 20 controls were included. All participants underwent ultrasonography of the thyroid and measurement of thyroid stimulating hormone (TSH). TSH levels were checked every 3 months. If hypothyroidism was present, T3, T4 and thyroid peroxidase autoantibodies were measured, and imaging extended to scintigraphy and repeated ultrasonography. RESULTS: Before treatment, 7 patients (14%) and 1 control (5%) were hypothyreotic. During the first 6 months of treatment, TSH levels increased in 41 patients (82%), 39 (78%) had values above the normal range and 19 (38%) had overt hypothyroidism. As none of the patients had signs of autoimmune thyroiditis, interaction with anti-tuberculosis drugs was assumed to be the cause of hypothyroidism. Nine patients died during treatment, all of whom had developed hypothyroidism. In seven, the metabolic situation at their death was known, and they had become euthyreotic following levothyroxine substitution. CONCLUSION: TSH levels should be checked before initiating anti-tuberculosis treatment and after 3 and 6 months to start timely replacement of levothyroxine. Further studies are needed to elucidate the exact pathomechanism involved in hypothyroidism and whether hypothyroidism can be used as predictor of treatment failure.

11C-methionine PET/CT after inconclusive 99mTc-MIBI-SPECT/CT for localisation of parathyroid adenomas in primary hyperparathyroidism.

AIM: To investigate the efficacy of PET/CT with 11C-methionine for localizing parathyroid adenomas in patients with suspected primary hyperparathyroidism and inconclusive results of cervical ultrasonography and 99mTc-MIBI-SPECT/CT. PATIENTS, METHOD: Retrospective analysis of imaging data of 18 patients and correlation with clinical outcome, in particular intraoperative findings and histopathology of excised tissue. RESULTS: 12 of 18 patients received surgery. In 10 patients single parathyroid adenomas were found (diameter: 5-20 mm), 2 patients presented parathyroid hyperplasia (5 excised hyperplastic glands (diameter: 2-12 mm). PET/CT correctly localized all adenomas and 1 of 5 hyperplastic glands. The sensitivity per patient was 91.7% (11 of 12), the sensitivity per lesion 73.3% (11 of 15). All lesions missed by PET/CT had a size smaller than 9 mm and a volume of less than 0.2 ml. In 6 patients no surgery was performed. Five of them had a negative or atypical PET/CT. Further follow-up indicated familial hypocalciuric hypercalcemia in 3 of them (thus, PET/CT true negative), in the remaining 2 patients no validation is available. One patient with 2 highly suggestive lesions rejected surgery so far. CONCLUSION: PET/CT with 11C-methionine is a very sensitive method for the detection of parathyroid adenomas, even if they are too small to be visualized by 99mTc-MIBI-SPECT/CT.

Peptide receptor radionuclide therapy of neuroendocrine tumors with (90)Y-DOTATOC: is treatment response predictable by pre-therapeutic uptake of (68)Ga-DOTATOC?

PURPOSE: PET with (68)Ga-DOTATOC allows for imaging and quantitative assessment of somatostatin receptor expression in neuroendocrine tumors (NET). The aim of this retrospective study was to analyze whether pre-therapeutic (68)Ga-DOTATOC PET/CT is able to predict response to Peptide Receptor Radionuclide Therapy (PRRT). PATIENTS AND METHODS: Forty patients with advanced stage NET were treated with a fixed dose of (90)Y-DOTATOC (5550 or 3700MBq). Prior to PRRT, each patient received (68)Ga-DOTATOC PET/CT. Treatment results were evaluated after 3months by CT, tumor marker levels and clinical course and correlated with (68)Ga-DOTATOC uptake (SUVmax) and the assumed uptake of (90)Y-DOTATOC in tumor manifestations (MBq/g). ROC analysis and pairwise comparison of area under the curve (AUC) were performed with pre-treatment uptake of (68)Ga-DOTATOC, assumed uptake of (90)Y-DOTATOC and treatment activity alone and in relation to body weight as continuous variables, and response/no response as classification variable. RESULTS: According to conventional criteria (tumor shrinkage, decrease of tumor markers, improved or stable clinical condition), 20 patients were classified as responders, 16 as non-responders and in four patients findings were equivocal. Using a SUV more than 17.9 as cut-off for favorable outcome, PET was able to predict treatment response of all responders and 15 out of 16 non-responders. All four patients with equivocal findings showed SUV less than or equal to 17.9 and soon experienced tumor progression. The assumed uptake of (90)Y-DOTATOC in tumor manifestations using a cut-off more than 1.26MBq/g as predictor of response was able to correctly classify 19 out of 20 responders, and 14 out of 16 non-responders. In all patients with equivocal findings, the assumed uptake of (90)Y-DOTATOC was below 1.26MBq/g. CONCLUSION: Pre-therapeutic (68)Ga-DOTATOC tumor uptake as well as assumed uptake of (90)Y-DOTATOC are strongly associated with the results of subsequent PRRT. The defined cut-off values should be confirmed by prospective studies and may then provide the rationale for individual dosing and selecting patients with high likelihood of favorable treatment outcome.

[Bone scintigraphy. German Guideline S1]. / Skelettszintigraphie. DGN-Handlungsempfehlung (S1-Leitlinie).

The purpose of this guideline is to provide comprehensive state-of-the-art information about indication and how to perform and analyze bone scintigraphy. Based upon pathophysiology and pharmacology current acquisition techniques including new methodologies are summarized followed by a detailed list of indications. In the main part all relevant practical aspects such as patient preparation, anamnestic information, appropriate choice and dosage of the radiopharmaceutical, and data acquisition including interventions are discussed. Data processing and analysis, interpretation, reporting and documentation are described in the next chapters. Quality control, typical pitfalls and a short outlook to future developments complete the guideline.

Modern imaging techniques during therapy in patients with multiple myeloma.

Imaging modalities used in the diagnosis of multiple myeloma have evolved and most of them are also suitable for either early or mid-term monitoring of response to novel antimyeloma therapy. This pictorial essay focuses on modern imaging techniques for diagnosis and follow-up of patients with multiple myeloma in order to highlight their individual strengths and limitations. Also, the impact of recently established modern pharmaceutical therapy, like anti-angiogenic medication, on the tumor is addressed.

[Procedure guideline for sentinel lymph node diagnosis]. / Verfahrensanweisung für die nuklearmedizinische Wächter-Lymphknoten-Diagnostik.

The authors present a procedure guideline for scintigraphic detection of sentinel lymph nodes in malignant melanoma and other skin tumours, in breast cancer, in head and neck cancer, and in prostate and penile carcinoma. Important goals of sentinel lymph node scintigraphy comprise reduction of the extent of surgery, lower postoperative morbidity and optimization of histopathological examination focussing on relevant lymph nodes. Sentinel lymph node scintigraphy itself does not diagnose tumorous lymph node involvement and is not indicated when lymph node metastases have been definitely diagnosed before sentinel lymph node scintigraphy. Procedures are compiled with the aim to reliably localise sentinel lymph nodes with a high detection rate typically in early tumour stages. Radiation exposure is low so that pregnancy is not a contraindication for sentinel lymph node scintigraphy. Even with high volumes of scintigraphic sentinel lymph node procedures surgeons, theatre staff and pathologists receive a radiation exposure <1 mSv/year so that they do not require occupational radiation surveillance.

Association of somatostatin receptor 2 immunohistochemical expression with [111In]-DTPA octreotide scintigraphy and [68Ga]-DOTATOC PET/CT in neuroendocrine tumors.

In the absence of preoperative somatostatin receptor ( SST) scans, knowledge of immunohistochemical SST2 tumor expression may help predicting the success of somatostatin analogue-based follow-up studies and treatment of neuroendocrine tumors (NET). We studied the association between SST immunostaining and tracer uptake in [(111)In]-DTPA octreotide (DTPAOC) scintigraphy and [(68)Ga]-DOTA-D-Phe(1)-Tyr(3)-octreotide (DOTATOC) positron emission tomography (PET)/computed tomography (CT). Retrospective analy-sis of 36 NET patients was carried out. In 40 tumors, immunohistochemical SST2, SST3, and SST5 expressions were analyzed using a pathological scoring, applying monoclonal ( SST2) or polyclonal antibodies (SST3, SST5). In 14 lesions, [(111)In]-DTPAOC uptake was assessed by a semiquantitative score. In 26 tumors, [(68)Ga]-DOTATOC PET/CT was quantified using an uptake score and maximal standard uptake value (SUV(max)). Combined and separate qualitative analysis of SST scans revealed significant associations between increased tracer uptake and immunohistochemical SST2 detection (combined: rho=0.56, p=0.0002, [(111)In]-DTPAOC: rho=0.63, p=0.0152, and [(68)Ga]-DOTATOC: rho=0.52, p=0.0065, respectively). In contrast, SST3 and SST5 immunostaining was not associated with tracer uptake (all p>0.14). The semiquantitative immunohistochemical score for SST2 was associated with the [(68)Ga]-DOTATOC uptake score and SUV (max) values (rho=0.67, p=0.0002 and rho=0.63, p=0.0010, respectively), but not with the [(111)In]-DTPAOC uptake score (rho=0.24, p=0.4). In patients without preoperative SST scans, knowledge of immunohistochemical SST2 expression may help estimating the value of SST imaging in the clinical follow-up, in particular in those lesions with positive SST2 immunostaining. Negativity for SST2, however, does not rule out tracer uptake in some patients, with heterogeneous SST2 expression within the tumor as a potential explanation.

Lymph node gastrinoma in multiple endocrine neoplasia type 1 - a diagnostic challenge.

BACKGROUND: Gastrinomas are the most frequent hormonally-active neuroendocrine tu-mours in patients with multiple endocrine neoplasia type 1 (MEN1). CASE REPORT: We report on the diagnostic difficulties in a 62-year-old female patient with MEN1 and lymph node gastrinoma. At six and twelve months after resection of a lymph node gastrinoma, no signs of recurrence were observed. Basal and peak gastrin levels during secretin stimulation test were normalized. Extensive explorations, including gastrointesinal endoscopy, endoscopic ultrasonography, and Ga-68-DOTATOC-PET/CT, did not reveal a primary duodenal or pancreatic tumour. CONCLUSION: Localization of gastrinomas in patients with MEN1 is challenging due to their small size, frequent duodenal location, and multiplicity. Therefore, while some studies support the existence of primary lymph node gastrinoma in patients with sporadic disease, this diagnosis should not be made in MEN1 patients. In both cases, however, extensive follow-ups are required.

[18F]-FDG-PET in clinical stage I/II non-seminomatous germ cell tumours: results of the German multicentre trial.

PURPOSE: The aim of this study was to determine the predictive values of 2-[fluorine-18]fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) in primary staging in patients with newly diagnosed non-seminomatous germ cell tumour (NSGCT) clinical stage I/II. PATIENTS AND METHODS: The hypothesis was that FDG-PET would improve the negative predictive value (NPV) from 70% to 90%, thus requiring a total of 169 patients. All scans underwent visual analysis by a reference team of nuclear medicine physicians. Results were validated by histology following retroperitoneal lymph node dissection. RESULTS: Only 72 of the planned 169 patients were included, due to poor accrual. The prevalence of nodal involvement was 26%. Correct nodal staging by FDG-PET was achieved in 83% compared with correct computed tomography (CT) staging in 71%. CT had a sensitivity and specificity of 41% and 95%, respectively. Positive predictive value (PPV) and NPV were 87% and 67%, respectively. FDG-PET had a sensitivity and specificity of 66% and 98%, respectively. PPV was 95%. The primary end point was not reached, with an NPV of 78%. CONCLUSION: FDG-PET as a primary staging tool for NSGCT yielded only slightly better results than CT. Both methods had a high specificity while false-negative findings were more frequent with CT. FDG-PET is mostly useful as a diagnostic tool in case of questionable CT scan.

Anxiety is associated with reduced central serotonin transporter availability in unmedicated patients with unipolar major depression: a [11C]DASB PET study.

Serotonergic dysfunction may contribute to negative mood states in affective disorders. Some in vivo imaging studies showed reduced availability of serotonin transporters (5-HTT) in the brainstem and thalamus of patients with major depression. We tested the hypothesis that 5-HTT availability is reduced in unmedicated unipolar patients with major depression compared to healthy control subjects matched for gender, age, genotype and smoking status. Availability of 5-HTT was measured in vivo with positron emission tomography and [(11)C]-3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile (DASB) in the midbrain, thalamus and amygdala. DASB binding was correlated with the severity of depression (Beck's Depression Inventory), anxiety (Spielberger's State-Trait Anxiety Inventory) and personality traits (Temperament and Character Inventory). Patients with major depression displayed reduced 5-HTT availability in the thalamus (P=0.005). In patients, low serotonin transporter availability correlated with high anxiety (thalamus: r=-0.78, P=0.004; midbrain: r=-0.78, P=0.004; amygdala: r=-0.80, P=0.003). Correlations with severity of depression were weaker and did not survive correction for multiple testing. These results support the hypothesis that central serotonergic dysfunction is associated with negative mood states in affective disorders. In the thalamus, a low serotonin reuptake capacity may interfere with thalamic control of cortical excitability and contribute to anxiety rather than depression per se in major depression.

Comparison of 11C-choline-PET/CT and whole body-MRI for staging of prostate cancer.

UNLABELLED: Aim of this study was to compare the diagnostic accuracy of positron emission tomography and computed tomography with (11)C-Choline (Cho-PET/CT) and whole body magnetic resonance imaging (WB-MRI) for diagnostic work-up of prostate cancer. PATIENTS, METHODS: We evaluated retrospectively 42 patients with untreated prostate cancer (n = 17), or increasing levels of prostate-specific antigen (PSA) after curative therapy (n = 25) who had been investigated by both Cho-PET/CT and WB-MRI. MRI, CT, and PET images were separately analyzed by experienced radiologists or nuclear medicine experts, followed by consensus reading. Validation was established by histology, follow-up, or consensus reading. RESULTS: 88/103 detected lesions were considered as malignant: 44 bone metastases, 22 local tumor, 15 lymph node metastases, 3 lung, and 3 brain metastases. One further lesion was located in the adrenal gland, which was a second tumor. Overall sensitivity, specificity and accuracy for Cho-PET/CT were 96.6%, 76.5%, and 93.3%, resp., and for WB-MRI 78.4%, 94.1%, and 81.0%, resp. 3 vertebral metastases had initially been missed by Cho-PET/CT and were found retrospectively. MRI identified 2 bone metastases and 1 lymph node metastasis after being informed about the results of Cho-PET/CT. CONCLUSIONS: Cho-PET/CT and WB-MRI both presented high accuracy in the detection of bone and lymph node metastases. The strength of MRI is excellent image quality providing detailed anatomical information whereas the advantage of Cho-PET/CT is high image contrast of pathological foci.

Reduced availability of serotonin transporters in obsessive-compulsive disorder correlates with symptom severity - a [11C]DASB PET study.

Reduced availability of brainstem serotonin transporters (5-HTT) has been observed in vivo in obsessive-compulsive disorder (OCD). However, results vary and may be influenced by competition with endogenous serotonin. Using positron emission tomography (PET) and [11C]DASB, a specific 5-HTT ligand that showed no competition with serotonin for 5-HTT binding in vitro, we tested the hypothesis that 5-HTT availability is reduced in OCD patients and correlated with OCD severity. METHODS. 5-HTT availability in the thalamus and the midbrain was measured in nine drug-free OCD patients and compared with 19 healthy controls, matched for the individual combination of 5-HTT genotype, gender and smoking status. OCD severity was assessed with the Yale-Brown obsessive compulsive scale (Y-BOCS). RESULTS. 5-HTT availability was significantly reduced in the thalamus and midbrain of OCD patients. Age and 5-HTT in the thalamus explained 83% of OCD severity in patients that were drug-free for at least 1 year. CONCLUSION. This PET study confirms a central role of the serotonergic system, particularly the thalamus in the pathogenesis of obsessive compulsive disorder.