Peptide and pseudo-peptide.

In recent years, the introduction of theranostic twins for specific diagnosis and treatment in patients with neuroendocrine tumors became a nuclear medicine success story. 64Cu/18F labeled prostate specific membrane antigen (PSMA) for molecular imaging with PET-CT and peptide radioligand therapy with 177Lu labeled PSMA inhibitors will favorably become the next theranostic twins in nuclear medicine history. 68Ga/ 64Cu/18F PSMA PET/CT detects metastatic prostate cancer with high diagnostic sensitivity and specificity. In addition, it can be used to select patients for radioligand therapy and evaluate therapy response. 64Cu-labeled radiopharmaceuticals such as 64Cu-PSMA, and 64Cu-somatostatin analogs are promising imaging tools in the assessment of primary disease and also in the detection of disease recurrence and to evaluate therapy response. The long half-life of 64Cu allows the distribution of the tracer to PET centers as a satellite concept, who otherwise has no access to 68Ga generators.

Surgery with Radical Intent: Is There an Indication for G3 Neuroendocrine Neoplasms?

BACKGROUND: While platinum-based chemotherapy represents the standard treatment for advanced grade 3 (G3) neuroendocrine neoplasms (NENs) according to the European Neuroendocrine Tumor Society guidelines, the role of radical-intended surgery in these patients, as well as the use of adjuvant chemotherapy, are still controversial. The aim of the present work is to describe, in a retrospective series of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) G3, the overall survival (OS) rate and risk factors for death after radical surgery. Secondary aims are the description of median recurrence-free survival (RFS) and of the role of adjuvant chemotherapy. PATIENTS AND METHODS: Multicenter analysis of a series of stage I-III GEP-NEN G3 patients receiving radical surgery (R0/R1) with/without adjuvant chemotherapy was performed. RESULTS: Sixty patients from eight neuroendocrine tumor (NET) referral centers, with median follow-up of 23 months (5-187 months) were evaluated. While 28.6% of cases had NET G3, 71.4% had neuroendocrine carcinoma G3 (NEC G3). The 2-year OS rate after radical surgery was 64.5%, with a statistically significant difference in terms of Ki67 threshold (cut-off 55%, P = 0.03) and tumor differentiation (NEC G3 vs. NET G3, P = 0.03). Median RFS after radical surgery was 14 months, and 2-year RFS rate was 44.9%. Use of adjuvant chemotherapy provided no benefit in terms of either OS or RFS in this series. CONCLUSIONS: Surgery with radical intent might represent a valid option for GEP-NEN G3 patients with locoregional disease, especially with Ki67 value ≤ 55%.

Downgrading of a G3 Neuroendocrine Tumor to a G2 Tumor: Can First-Line Cytotoxic Chemotherapy Change the Tumor Biology?

The antiproliferative treatment options for neuroendocrine tumors (NET)/neuroendocrine carcinomas of the gastrointestinal tract critically depend on the proliferation rate, evaluated by immunohistochemical staining for Ki-67. According to their grading, tumors are treated with somatostatin analogs, mTOR inhibitors, or cytotoxic substances. This case illustrates downgrading of a primarily highly proliferative NET achieved by a variation of cytotoxic chemotherapy regimens, followed by a combination therapy using everolimus together with lanreotide. The latter medication might lead to a good clinical response as far as tumor growth is concerned.

The value of FDG-PET in the diagnosis of thromboangiitis obliterans--a case series.

Thromboangiitis obliterans (TAO) is an inflammatory vascular disease affecting dominantly the vessels of the extremities and is etiologically strongly associated with tobacco consumption. Different imaging techniques are generally used to exclude potential differential diagnoses. We investigated the value of (18) F-flourodeoxyglucose positron emission tomography ([(18) F]FDG-PET) in the diagnosis of TAO. All consecutive patients with diagnosed TAO between Nov 2001 and Nov 2003 at our institution who underwent [(18) F]FDG-PET in the diagnostic workup were analyzed retrospectively. Whole-body scans were conducted after a fasting period of at least 6 h and blood glucose levels lower than 180 mg/dl. The primary endpoint was defined as significantly increased vascular FDG uptake. Tracer uptake was visually determined and, in accordance with strength, divided into grades 0 to 3. In total, ten patients were statistically evaluated. The median patient age at the date of the first [(18) F]FDG-PET was 41.5 years. Repetitive FDG-PET imaging was performed in seven out of ten patients (70 %). The endpoint was objectified in one of the initial examinations (10 %) and in another one out of seven follow-up scans (14.3 %). One positive [(18) F]FDG-PET was observed in the pelvic vessels and the other in the infrapopliteal arteries. Therefore, increased tracer uptake could be observed in two examinations on two different patients (both with grade 3 tracer uptake) out of 17 conducted [(18) F]FDG-PETs in total. The [(18) F]FDG-PET was not a suitable investigative procedure for the diagnosis of TAO in the present patient cohort.

Improvement of Cerebral Hypoperfusion with Levothyroxine Therapy in Hashimoto's Encephalopathy Demonstrated by (99m)Tc-HMPAO-SPECT.

BACKGROUND: Hashimoto's encephalopathy (HE) is a rare immune-mediated encephalopathy associated with autoimmune Hashimoto's thyroiditis. OBJECTIVES AND METHODS: We report on a patient with HE and significant clinical improvement correlating with an increase in cerebral blood flow demonstrated by hexamethylpropyleneamine oxime (HMPAO) single-photon emission computed tomography (SPECT). HMPAO-SPECT was performed with 740 MBq of technetium-99m-HMPAO. To demonstrate the improvement in regional cerebral blood flow, individual regions of interest were drawn around visually diminished HMPAO uptake, the lesion to reference region ratio was calculated and transverse section images and semi-quantitative measurements were performed. RESULTS: We show a 5-year follow-up with significant clinical improvement, a 10-fold reduction in autoantibodies to thyroid peroxidase and an approximately 20% improvement in cerebral blood flow with HMPAO-SPECT. CONCLUSION: Adequate levothyroxine treatment achieving and maintaining euthyroidism should be considered as therapy to lower autoantibodies and improve clinical outcome in patients with Hashimoto's thyroiditis and encephalopathy.

Additional lesions detected in therapeutic scans with 177Lu-DOTATATE reflect higher affinity of 177Lu-DOTATATE for somatostatin receptors.

OBJECTIVE: Peptide receptor-targeted radionuclide therapy (PRRT) of somatostatin receptor (SR)-expressing neuroendocrine tumors (NETs) has become an established therapeutic option in patients with advanced NETs. The aim of this study was to compare the lesion detection rate of (99m)Tc-EDDA/HYNIC-TOC, a newly developed tracer for NET imaging, with (177)Lu-DOTATATE used for PRRT. METHODS: 8 patients (4 women, 4 men, age range 46-76 years) with histologically proven NETs, who showed high SR loads by (99m)Tc-EDDA/HYNIC-TOC scintigraphy, were treated with (177)Lu-DOTATATE. After treatment, all patients were subjected to whole-body scintigraphy with additional low-dose single-photon emission computed tomography (SPECT-CT) of the chest and abdomen. RESULTS: All patients demonstrated (177)Lu-DOTATATE accumulation in all lesions previously detected by (99m)Tc- EDDA/HYNIC-TOC scintigraphy. Three patients showed additional lesions in the liver and lungs. CONCLUSIONS: SPECT-CT after (177)Lu-DOTATATE therapy may be helpful in detecting additional lesions not seen using (99m)Tc-EDDA/HYNIC-TOC. This could reflect the broader affinity of (177)Lu-DOTATATE for SRs compared with (99m)Tc-EDDA/HYNIC-TOC.

Insights into epiploic appendagitis.

Epiploic appendagitis is a rare cause of abdominal pain. Diagnosis of epiploic appendagitis, although infrequent, is easily made with CT or ultrasonography in experienced hands. As reported in the literature, most patients with primary epiploic appendagitis are treated conservatively without surgery, with or without anti-inflammatory drugs. A small number of patients are treated with antibiotics and some patients require surgical intervention to ensure therapeutic success. Symptoms of primary epiploic appendagitis usually resolve with or without treatment within a few days. A correct diagnosis of epiploic appendagitis with imaging procedures enables conservative and successful outpatient management of the condition and avoids unnecessary surgical intervention and associated additional health-care costs. Gastroenterologists and all medical personnel should be aware of this rare disease, which mimics many other intra-abdominal acute and subacute conditions, such as diverticulitis, cholecystitis and appendicitis. This article reviews epiploic appendagitis and includes discussion of clinical findings, pathophysiology, diagnosis and therapeutic possibilities.

Patent abdominal subcutaneous veins caused by congenital absence of the inferior vena cava: a case report.

INTRODUCTION: Patent paraumbilical and abdominal subcutaneous veins are found frequently as collaterals in patients due to portal hypertension mainly in liver cirrhosis. CASE PRESENTATION: For evaluation of portal hypertension in a 72-year-old Caucasian man without liver cirrhosis, magnetic resonance imaging with gadolinium contrast-enhancement was performed and demonstrated a missing inferior vena cava. A blood return from the lower extremities was shown through enlarged collateral veins of the abdominal wall, vena azygos and hemiazygos continuation, and multiple liver veins emptying into the right cardiac atrium. We describe a rare case of abdominal subcutaneous wall veins as collaterals caused by a congenitally absent infrarenal inferior vena cava with preservation of a hypoplastic suprarenal segment. CONCLUSION: Knowledge of these congenital variations can be of clinical importance and it is imperative for the reporting radiologist to identify these anomalies as they can have a significant impact on the clinical management of the patient.

Agenesis of the dorsal pancreas.

During the last 100 years in medical literature, there are only 54 reports, including the report of Pasaoglu et al (World J Gastroenterol 2008; 14: 2915-2916), with clinical descriptions of agenesis of the dorsal pancreas in humans. Agenesis of the dorsal pancreas, a rare congenital pancreatic malformation, is associated with some other medical conditions such as hyperglycemia, abdominal pain, pancreatitis and a few other diseases. In approximately 50% of reported patients with this congenital malformation, hyperglycemia was demonstrated. Evaluation of hyperglycemia and diabetes mellitus in all patients with agenesis of the dorsal pancreas including description of fasting blood glucose, oral glucose tolerance test, glycated hemoglobin and medical treatment would be a future goal. Since autosomal dominant transmission has been suggested in single families, more family studies including imaging technologies with demonstration of the pancreatic duct system are needed for evaluation of this disease. With this letter to the editor, we aim to increase available information for the better understanding of this rare disease.

Agenesis of the dorsal pancreas and associated diseases.

BACKGROUND: Agenesis of the dorsal pancreas is a very rare congenital pancreatic malformation and is associated with some other diseases. METHODS: A PubMed search revealed 53 cases of agenesis of the dorsal pancreas. RESULTS: In 28 patients with this congenital malformation hyperglycemia was demonstrated, 27 had abdominal pain, 16 had pancreatitis, 14 had an enlarged or prominent pancreatic head visible on computed tomography, and in a few cases, polysplenia, which may occur with various congenital anomalies of visceral organs, was described. CONCLUSIONS: Difficulties involved in obtaining a firm diagnosis have led to a variety of terms being used to describe this congenital disease. Diagnosis of agenesis of the dorsal pancreas is inconclusive without demonstration of the absence of the dorsal pancreatic duct. Here we describe the embryological development of the pancreas, the so-far known cases of agenesis of the dorsal pancreas with associated medical problems, and the diagnostic measures to find the right conclusions.

99mTc-apcitide scintigraphy in patients with clinically suspected deep venous thrombosis and pulmonary embolism.

AIM: Detection of acute deep venous thrombosis (DVT) in patients presenting with clinical symptoms suggesting DVT and pulmonary embolism (PE) with (99m)Tc-apcitide, a synthetic polypeptide, binding to glycoprotein IIb/IIIa receptors expressed on activated platelets is the objective of the study. MATERIALS AND METHODS: Nineteen patients (11 males, eight females) received within 24h after admission to the hospital a mean of 841 MBq (range 667 to 1,080) (99m)Tc-apcitide i.v. followed by planar recordings 10, 60, and 120 min after injection. Images were compared to the results of compression ultrasonography and/or phlebography. Patients with clinically suspected PE underwent spiral computed tomography or lung perfusion scans. RESULTS: (99m)Tc-apcitide scintigraphy showed acute clot formation in 14 out of 16 patients where the other imaging modalities suggested DVT. Positive scintigraphic results were seen up to 17 days after the onset of clinical symptoms. In three out of three patients without any proof of DVT, (99m)Tc-apcitide scintigraphy was truly negative. Glycoprotein receptor imaging showed only one segmental PE in six patients with imaging-proven subsegmental (N = 3) or segmental PE (N = 3). CONCLUSION: (99m)Tc-apcitide scintigraphy may be an easy and promising tool for the detection of acute clot formation in patients with DVT up to 17 days after the onset of clinical symptoms with a sensitivity of 87% and a specificity of 100%. However, it failed to demonstrate PE in 83% of examined patients with proven PE.

Relationships between body fat measured by DXA and subcutaneous adipose tissue thickness measured by Lipometer in adults.

The aim of this study was to examine the relationships between body fat measured by DXA and subcutaneous adipose tissue layers (SAT-layers) measured by LIPOMETER in adult males (n=28) and females (n=53). Body height and mass were measured and BMI was calculated (kg/m2). Measurements of the thicknesses of SAT-layers by LIPOMETER were performed at 15 original body sites. Body composition was measured using DXA. Total body fat % measured by DXA was highly dependent on the SAT-layers in the upper back and inner thigh in males (87.1%, R(2)x100) and the lateral chest, biceps, and calf in females (78.5%, R(2)x100). There were gender differences in trunk fat mass and right hand and leg fat mass calculation using specific SAT-layers. In conclusion, our results indicate that there are close relationships between SAT-layers and body fat measured by DXA. However, there are big differences between genders.

Evaluation of conditions associated with glycated hemoglobin values below the reference range.

BACKGROUND: Evaluation of conditions associated with glycated hemoglobin (HbA1c) values below the reference range in HbA1c determinations. METHODS: Over a time period of 5 years, HbA1c results were determined with the ion-exchange high-performance liquid chromatography (HPLC) method HA-8140 Menarini. RESULTS: Of approximately 20 000 HbA1c results analyzed, 9 were below the reference range. The reason for HbA1c values below the reference range was found to be liver cirrhosis in 6 patients, anemia with hematological neoplasms in 2 patients, and elevated fetal hemoglobin > 1.5% in one patient. The silent hemoglobin (Hb) variant Hb Graz in 6 patients, Hb Sherwood Forest in 1 patient, homozygote HbS in one patient, and gross hypertriglyceridemia in one patient demonstrated no HbA1c result. CONCLUSIONS: In patients with liver cirrhosis, HbA1c measurements should be used with caution when evaluating long-term glucose control, and samples with suspected Hb variants should be analyzed by hemoglobin electrophoresis. Our study underscores the need for clinical laboratories and physicians to be aware of the limitations of their HbA1c assay methods as well as of the importance of visual inspection of ion-exchange chromatograms to detect HbA1c values below the reference range and abnormalities caused by the interference factors described here.

Three-dimensional gadolinium-enhanced magnetic resonance angiography used as a "one-stop shop'' imaging procedure for venous thromboembolism: a pilot study.

Pulmonary embolism and deep venous thrombosis are individual manifestations of a single entity, venous thromboembolic disease. This study aimed to assess the feasibility of 3-dimensional gadolinium-enhanced magnetic resonance angiography used as an "one-stop shop'' imaging procedure visualizing both the pulmonary arteries and the deep lower venous system within a single investigation. The inclusion criterion was a proven or excluded venous thromboembolism. Diagnosis was based on an imaging work-up for pulmonary embolism including either perfusion lung scan or contrast-enhanced spiral computed tomography, or both, and an imaging work-up for deep venous thrombosis including either venous color-coded duplex sonography or ascending phlebography, or both. A gadolinium-enhanced "one-stop shop'' magnetic resonance angiography was performed within 24 hours of completed diagnostic imaging work-up for pulmonary embolism and deep venous thrombosis in 20 patients. Results of pulmonary magnetic resonance angiography were concordant with perfusion lung scan and/or computed tomography in 90% of patients. Magnetic resonance angiography results of the deep lower venous system were concordant with venous duplex sonography and/or phlebography in 75% of patients and seemed to be more precise in 25% of patients. The "one-stop shop'' imaging procedure using gadolinium-enhanced magnetic resonance angiography was feasible and proved to offer a reliable and rapid diagnostic approach in thromboembolic disease, sparing patients' exposure to ionizing radiation and iodinated contrast media.