Case report - Selective internal radiation therapy (SIRT) in a patient with hyperinsulinemic hypoglycemia due to a metastatic insulinoma with late onset of endocrine activity.

Insulinomas are the most common functioning pancreatic neuroendocrine tumors (NET), which can lead to hyperinsulinemic hypoglycemia. In advanced metastatic stages of the disease, the prognosis is poor. Patients with hormonally active insulinomas primarily present with features of neuroglycopenia. Transformation from a nonfunctional to a functional NET is rare. Here, we present a case of a 59-year-old male adult with a metastatic insulinoma and late onset of endocrine activity. Besides medical treatment with Diazoxide and small frequent feedings, continuous intravenous glucose application was eventually required to avoid hypoglycemia. Furthermore, we show that selective internal radiation therapy (SIRT) can be an effective therapeutic approach for symptom reduction in advanced metastatic disease.

Analysis of Periprocedural X-ray Exposure in Transarterial Radioembolization with Glass or Resin Microspheres.

Background: Transarterial Radioembolization (TARE) is an effective treatment option for both primary and secondary liver malignancies. However, challenging anatomical conditions can lead to prolonged fluoroscopy times (FT), elevated doses of periprocedural X-radiation (DAP), and increased use of contrast agents (CAs). In this study, we examined the influence of our radiologists' experience and the choice of microspheres on X-ray exposure and CA doses in TARE. Material and Methods: Datasets comprising 161 TARE and 164 preprocedural evaluation angiographies (TARE-EVA) were analyzed. Our study focused on assessing DAP, FT, and CA concerning both microsphere types, the radiologist's experience, and whether the same radiologist performed both the TARE-EVA and the actual TARE. Results: In TARE, the use of resin microspheres resulted in significantly higher FT and CA compared to glass microspheres (14.3 ± 1.6 min vs. 10.6 ± 1.1 min and 43 ± 2.2 mL vs. 33.6 ± 2.1 mL, p < 0.05), with no notable differences in DAP (p = 0.13). Experienced radiologists demonstrated reduced FT/DAP, with a 19% decrease in DAP and 53% in FT during the evaluation angiography (p < 0.05) and a 49% reduction in DAP during the actual TARE (p < 0.05), with no statistical differences in FT. Performing TARE and TARE-EVA under the same radiologist led to a 43% reduction in DAP and a 25% decrease in FT (p < 0.05, respectively). Conclusions: To mitigate X-radiation exposure, it is advisable for radiologists to undergo thorough training, and, ideally, the same radiologist should conduct both the TARE and the TARE-EVA. While the use of glass spheres may decrease intraarterial CA, it does not significantly impact periprocedural X-ray exposure.

The Liver Maximum Capacity Test (LiMAx) Is Associated with Short-Term Survival in Patients with Early Stage HCC Undergoing Transarterial Treatment.

Transarterial chemoembolization (TACE) and transarterial radioembolization (TARE) are recommended to treat patients with early or intermediate hepatocellular carcinoma (HCC). The liver maximum capacity test (LiMAx) has been supposed to predict the risk of post-interventional liver failure. We investigated the correlation of LiMAx with short-term survival as primary endpoint and the occurrence of adverse events after therapy as secondary endpoint. Our study cohort prospectively included 69 patients receiving TACE (n = 57) or TARE (n = 12). LiMAx test and serological analyses were performed on the day before and 4 weeks after treatment. Hepatic and extrahepatic complications were monitored for 4 weeks. The LiMAx results were not associated with altered liver function and the occurrence of adverse events. The survival rates of patients with BCLC A with LiMAx ≤ 150 µg/kg/h were lower after 30 days (75.0 ± 15.3% vs. 100%, p = 0.011), 90 days (62.5 ± 17.7% vs. 95.8 ± 4.1%, p = 0.011) and 180 days (50.0 ± 17.7% vs. 95.8 ± 4.1%, p = 0.001) compared to those with higher LiMAx levels. The LiMAx test is not suitable to predict liver function abnormalities or the occurrence of complications 4 weeks after therapy but enables the identification of patients with early stage HCC and reduced short-term survival after treatment.

Anti VEGF-TKI Treatment and New Renal Adverse Events Not Reported in Phase III Trials.

Cabozantinib and lenvatinib have been approved for the treatment of progressive medullary thyroid cancer and radioiodine-resistant thyroid cancer, respectively. Both phase III trials of cabozantinib and lenvatinib reported that renal adverse events (AEs) rarely occurred. The cabozantinib phase III study reported no AEs related to renal toxicity. In the lenvatinib phase III trial grade 3 (CTCAE), proteinuria (urinary protein ≥3.5 g/24 h) was found in 10.0% of the lenvatinib and 0.0% of the placebo patients. We report a 23-year-old patient with metastatic medullary thyroid cancer who was enrolled in the phase III trial, comparing cabozantinib to placebo and a 67-year-old patient with metastatic, papillary thyroid carcinoma who was undergoing treatment with lenvatinib during his enrollment in the phase III trial. The first patient had a normal kidney function initially, but developed end-stage chronic kidney disease unexpectedly on cabozantinib and additional zoledronate infusion. Whereas the second patient suffered from a dramatic aggravation of his known mild chronic renal insufficiency (KDOQI stage 2) due to long standing hypertension and atherosclerosis during the treatment with lenvatinib. These severe AEs due to anti-VEGF tyrosine kinase inhibitor treatment were unknown so far. In conclusion, these 2 cases argue for increased awareness for the possibility of renal failure as a consequence of anti-VEFG treatment. Predisposing conditions like known mild chronic renal insufficiency with only mild proteinuria and with atherosclerosis or precipitating co-medications like zoledronate infusion need to be accounted for to prevent these severe AEs.

Ectopic Cushing' syndrome caused by a neuroendocrine carcinoma of the mesentery.

BACKGROUND: ACTH overproduction within the pituitary gland or ectopically leads to hypercortisolism. Here, we report the first case of Cushing' syndrome caused by an ectopic ACTH-secreting neuroendocrine carcinoma of the mesentery. Moreover, diagnostic procedures and pitfalls associated with ectopic ACTH-secreting tumors are demonstrated and discussed. CASE PRESENTATION: A 41 year-old man presented with clinical features and biochemical tests suggestive of ectopic Cushing's syndrome. First, subtotal thyroidectomy was performed without remission of hypercortisolism, because an octreotide scan showed increased activity in the left thyroid gland and an ultrasound revealed nodules in both thyroid lobes one of which was autonomous. In addition, the patient had a 3 mm hypoenhancing lesion of the neurohypophysis and a 1 cm large adrenal tumor. Surgical removal of the pituitary lesion within the posterior lobe did not improve hypercortisolism and we continued to treat the patient with metyrapone to block cortisol production. At 18-months follow-up from initial presentation, we detected an ACTH-producing neuroendocrine carcinoma of the mesentery by using a combination of octreotide scan, computed tomography scan, and positron emission tomography. Intraoperatively, use of a gamma probe after administration of radiolabeled (111)In-pentetreotide helped identify the mesenteric neuroendocrine tumor. After removal of this carcinoma, the patient improved clinically. Laboratory testing confirmed remission of hypercortisolism. An octreotide scan 7 months after surgery showed normal results. CONCLUSION: This case underscores the diagnostic challenge in identifying an ectopic ACTH-producing tumor and the pluripotency of cells, in this case of mesenteric cells that can start producing and secreting ACTH. It thereby helps elucidate the pathogenesis of neuroendocrine tumors. This case also suggests that patients with ectopic Cushing's syndrome and an octreotide scan positive in atypical locations may benefit from explorative radioguided surgery using (111)In-pentetreotide and a gamma probe.

Serotonin and dopamine transporter imaging in patients with obsessive-compulsive disorder.

In obsessive-compulsive disorder (OCD), the success of pharmacological treatment with serotonin re-uptake inhibitors and atypical antipsychotic drugs suggests that both the central serotonergic and dopaminergic systems are involved in the pathophysiology of the disorder. We applied [123I]-2beta-carbomethoxy-3beta-(4-idiophenyl)tropane (beta-CIT) and a brain-dedicated high-resolution single photon emission computed tomography (SPECT) system to quantify dopamine transporter (DAT) and serotonin transporter (SERT) availability. By comparing 15 drug-naïve patients with OCD and 10 controls, we found a significantly reduced availability (corrected for age) of striatal DAT and of thalamic/hypothalamic, midbrain and brainstem SERT in OCD patients. Severity of OCD symptoms showed a significant negative correlation with thalamic/hypothalamic SERT availability, corrected for age and duration of symptoms. Our data provide evidence for imbalanced monoaminergic neurotransmitter modulation in OCD. Further studies with more selective DAT and SERT radiotracers are needed.

The Treatment of Well-Differentiated Thyroid Carcinoma.

BACKGROUND: Recent decades have seen a rise in the incidence of well-differentiated (mainly papillary) thyroid carcinoma around the world. In Germany, the age-adjusted incidence of well-differentiated thyroid carcinoma in 2010 was 3.5 per 100 000 men and 8.7 per 100 000 women per year. METHODS: This review is based on randomized, controlled trials and multicenter trials on the treatment of well-differentiated thyroid carcinoma that were retrieved by a selective literature search, as well as on three updated guidelines issued in the past two years. RESULTS: The recommended extent of surgical resection depends on whether the tumor is classified as low-risk or high-risk, so that papillary microcarcinomas, which carry a highly favorable prognosis, will not be overtreated. More than 90% of localized, well-differentiated thyroid carcinomas can be cured with a combination of surgery and radioactive iodine therapy. Radioactive iodine therapy is also effective in the treatment of well-differentiated thyroid carcinomas with distant metastases, yielding a 10-year survival rate of 90%, as long as there is good iodine uptake and the tumor goes into remission after treatment; otherwise, the 10-year survival rate is only 10%. In the past two years, better treatment options have become available for radioactive-iodine-resistant thyroid carcinoma. Phase 3 studies of two different tyrosine kinase inhibitors have shown that either one can markedly prolong progression-free survival, but not overall survival. Their more common clinically significant side effects are hand-foot syndrome, hypertension, diarrhea, proteinuria, and weight loss. CONCLUSION: Slow tumor growth, good resectability, and susceptibility to radioactive iodine therapy lend a favorable prognosis to most cases of well-differentiated thyroid carcinoma. The treatment should be risk-adjusted and interdisciplinary, in accordance with the current treatment guidelines. Even metastatic thyroid carcinoma has a favorable prognosis as long as there is good iodine uptake. The newly available medical treatment options for radioactive-iodine-resistant disease need to be further studied.

Serial 18F-fluoro-2-deoxy-D-glucose positron emission tomography and magnetic resonance imaging of paraneoplastic limbic encephalitis.

OBJECTIVES: To review and expand the existing literature of magnetic resonance imaging (MRI) and positron emission tomography (PET) of paraneoplastic limbic encephalitis (PLE). METHODS: We performed serial MRI and 18F-fluoro-2-deoxy-D-glucose (FDG)-PET in a patient with anti-Ma2-positive PLE. In addition, we reviewed the relevant literature by conducting a search in the Medline database. RESULTS: We found a total of 7 published patient studies of possible or probable PLE containing both MRI and PET data. In 1 of these reports, the diagnosis of PLE can be regarded as proven. The results of the previous studies are controversial. Epileptic activity and inflammation are assumed to be underlying mechanisms of increased FDG uptake. In our study, we found a focal tracer accumulation in the left medial temporal lobe, which increased during the first 9 months of follow-up and corresponded with an increase of serum anti-Ma2 antibody titers. The MRI findings showed a hyperintense signal change in the left medial temporal lobe without contrast enhancement, which remained unchanged over time. CONCLUSIONS: The results of functional and structural imaging in PLE may differ substantially. Results of FDG-PET can demonstrate focal hypermetabolism over a long time, which may indicate therapeutic potential. A prospective study with more patients will be needed to clarify the relevance of PET as a possible outcome measure in PLE. Future studies should include scalp or semi-invasive electroencephalographic recordings during PET acquisition.

Investigating dopaminergic neurotransmission with 123I-FP-CIT SPECT: comparability of modern SPECT systems.

UNLABELLED: With (123)I-labeled N-omega-fluoropropyl-2-beta-carbomethoxy-3-beta-(4-iodophenyl)nortropane (FP-CIT) SPECT increasingly gaining access into routine patient care, the comparability of the results of different SPECT systems in the quantification of receptor binding is important for accurate clinical decision making and the translation of imaging results between institutions (e.g., as part of multicenter therapy trials). METHODS: In a series of studies using phantoms (containing target cylinders of 2- and 2.8-cm diameter) and (123)I-FP-CIT patient studies (n = 49), we compared target-to-background (T/BG) and (123)I-FP-CIT striatal uptake ratios recovered by a conventional triple-head SPECT system and a dedicated high-resolution brain SPECT system. All patient studies were acquired on both SPECT systems successively (<15-min interscan gap) using a single-injection protocol (group A [n = 20] was first scanned on the triple-head SPECT system, and group B [n = 29] was first scanned on the dedicated brain SPECT system). RESULTS: In phantom studies, the T/BG ratios recovered by both systems correlated strongly with the true T/BG ratios (R(2) > 0.96), with the linear regression slopes being 0.86-1.17 and 0.41-0.52 (less steep for smaller target size and lower T/BG ratios) for the dedicated brain SPECT and the triple-head SPECT system, respectively. Although both systems yielded markedly different results, they showed a high linear correlation with each other (R(2) > 0.95, no significant effect from target size). In (123)I-FP-CIT patient studies, a similar linear intersystem correlation was found (R(2) [A/B] = 0.79/0.80, 0.52/0.68, and 0.83/0.85 for the uptake ratios of the striatum, caudate, and putamen, respectively, to the occipital reference region). CONCLUSION: A linear transformation of striatal uptake ratios between different SPECT systems appears to be achievable for ligands such as (123)I-FP-CIT. An evaluation is needed of whether the present method can do this with sufficient accuracy for clinical purposes or whether methodologic adaptations are necessary. Proper study timing has to be ensured.

Quality of life in patients with thyroid cancer compared with the general population.

BACKGROUND: Since patients with thyroid cancer have a very good prognosis overall, clinicians may often assume that their quality of life is comparable to the general population. We hypothesized that quality of life of thyroid cancer patients is lower compared with the general population while controlling the effect of age and gender. METHODS: At the beginning of their stay at an inpatient rehabilitation clinic, a cohort of n=121 patients with thyroid cancer were assessed using the quality of life core questionnaire of the European Organisation for Research and Treatment of Cancer (QLQ-C30). Data for comparison were derived from a representative German community sample with n=2037. RESULTS: The patients reported significantly more problems than the community sample participants independent of gender and age effects in all but two domains, namely constipation and diarrhea. The strongest effects of the group (patients vs. general population) were found in the following domains: insomnia (B=-43.7, p<0.001), fatigue (B=-38.0, p=<0.001), and role functioning (B=29.7, p=<0.001). Significant interactions between age and group occurred in the social functioning, role functioning, fatigue, nausea/vomiting, and financial difficulties domains. Quality of life was unrelated to the stage of the disease, except in the physical function and global health status domains. CONCLUSIONS: At the beginning of inpatient rehabilitation, patients with thyroid cancer often experience more problems than controls from community samples, independent of their age and gender. Clinicians should be aware of the fact that quality of life is not directly related to the severity of the cancer prognosis.

A patient with a large recurrent pheochromocytoma demonstrating the pitfalls of diagnosis.

BACKGROUND: A 59-year-old man presented for a follow-up, 6 years after surgery for a large pheochromocytoma. He had suffered from diabetes mellitus, hypertension and abdominal pain in the right flank region. Previous postoperative follow-up did not reveal tumor recurrence. INVESTIGATION: Measurement of plasma free metanephrine and normetanephrine by high-performance liquid chromatography and radioimmunoassay; 123I-metaiodobenzylguanidine (MIBG) scintigraphy; hybrid 123I-MIBG single-photon emission CT (SPECT)-CT; MRI; testing for plasma norepinephrine and epinephrine; intraoperative ultrasonography; histological staining for chromogranin A and synaptophysin; and postoperative 18F-dihydroxyphenylalanine (DOPA) PET scan. DIAGNOSIS: Recurrent pheochromocytoma. MANAGEMENT: Laparotomy with tumor resection. Reduction of antihypertensive medications. Further follow-up by MRI, hybrid 123I-MIBG SPECT-CT and testing for plasma catecholamines and free metanephrines.

Relative quantification of indium-111 pentetreotide and gallium-68 DOTATOC uptake in the thyroid gland and association with thyroid pathologies.

BACKGROUND: Recent data suggest that increased somatostatin receptor (SSTR) expression is detectable in several thyroid diseases. This raises the question as to the specificity and pathophysiologic relevance of these findings. Therefore, we systematically evaluated Indium-111 (In-111) pentetreotide scintigraphies and Gallium-68 (Ga-68) DOTA-Phe(1)-Tyr(3)-Octreotide (DOTATOC) positron emission tomography (PET) scans for thyroid radiotracer uptake. METHODS: Relative binding of In-111 pentetreotide in the thyroid was measured by region of interest (ROI) technique in 4-hour and 24-hour post-injection (p.i.) planar images of 73 patients undergoing In-111 pentetreotide scintigraphy. Ga-68 DOTATOC PET scans of 77 patients were analyzed by ROI technique applied to coronal slices of 1 cm (0.39 inch) thickness with highest uptake in the thyroid region. RESULTS: A basal indium In-111 and Ga-68 DOTATOC uptake was found in normal thyroid glands. Hot nodules, disseminated thyroid autonomy, and most cases of active Hashimoto's disease as well as goiters and nodular thyroids showed increased In-111 pentetreotide and/or Ga-68 DOTATOC uptake. Higher relative In-111 pentetreotide uptake in the 24-hour p.i. images as compared to the 4-hour p.i. images except for patients after thyroidectomy indicates specific receptor binding in the thyroid. CONCLUSIONS: The increased In-111 pentetreotide and Ga-68 DOTATOC uptake in active Hashimoto's disease is most likely related to the lymphocytic infiltration of the thyroid. However, the physiologic or pathophysiologic relevance of the increased In-111 pentetreotide and Ga-68 DOTATOC uptake in normal thyroid glands, hot and cold nodules, and goiters and nodular thyroids remain to be determined.