Prospective Within-Patient Assessment of the Impact of an Unlabeled Octreotide Pre-dose on the Biodistribution and Tumor Uptake of 68Ga DOTATOC as Assessed by Dynamic Whole-body PET in Patients with Neuroendocrine Tumors: Implications for Diagnosis and Therapy.

PURPOSE: Gastroenteropancreatic neuroendocrine tumors (GEP NETs) are often associated with high expression of somatostatin receptors (SSTRs) which allows for PET/CT imaging with radiolabeled somatostatin analogs such as 68Ga-DOTATOC. The interplay between 68Ga-DOTATOC and the synthetic somatostatin analogs commonly used to manage patient symptoms may lead to competition between the labelled and unlabeled peptides for receptor binding sites and current product labelling recommends patients be taken off somatostatin analogs before imaging. In this study, we prospectively investigated in human patients the effect of a pre-dose of octreotide, a short-acting somatostatin analog, on the distribution of 68Ga-DOTATOC in GEP NETs and normal organs. PROCEDURE: Research participants with GEP NETs were studied on two occasions using dynamic whole-body 68Ga-DOTATOC PET/CT. The two imaging studies were performed within 21 days of each other, using an identical acquisition protocol except for the administration of 50 µg of short-acting octreotide (pre-dose) immediately before the second PET/CT. Paired t-tests were used to compare tracer uptake with and without octreotide, for tumor and various normal organs. RESULTS: Seven participants with a mean age of 53 ± 10 years were studied. Octreotide pre-dosing decreased radiotracer uptake in the normal liver and spleen by 25 % (p = 0.04) and 47 % (p = 0.05) respectively but did not significantly change uptake in tumor (p = 0.53), red marrow (p = 0.12), kidneys (p =0.57), or pituitary gland (p = 0.27). CONCLUSIONS: Our data indicate SSTR imaging can be improved with a pre-dose of unlabeled octreotide given just prior to injection of the radiotracer. These data suggest there may be no need to discontinue somatostatin analog therapy prior to PET/CT with 68Ga-DOTATOC, allowing for a simpler, less disruptive patient protocol. This approach warrants further study in a variety of settings.

Isolated perforated jejunal diverticulitis: a case report.

Jejunal diverticulosis is a rare phenomenon often identified either incidentally on imaging or intra-operatively. Complications of jejunal diverticulosis are associated with high rates of mortality. For this reason, it remains important that this pathology is considered amongst differentials for an acute abdomen. A 78-year old gentleman presented with a short history of generalized lower abdominal pain. Computer tomography scan revealed a large inflammatory abscess relating to a perforated jejunal diverticulum. The patient was taken to theatre where he underwent small bowel resection with primary anastomosis. Early cross sectional imaging is vital to allow early diagnosis and prompt management of this pathology. Small bowel resection with primary anastomosis was associated with an excellent clinical outcome.

The Na/K-ATPase α1 and c-Src form signaling complex under native condition: A crosslinking approach.

The protein-protein interactions amongst the Na/K-ATPase α1 subunit, c-Src, and caveolin-1 (cav-1) are essential for the Na/K-ATPase signaling functions. However, there are arguments concerning the interaction model. The present study aims to clarify the interactions amongst the endogenous native proteins in live cells under native resting condition. Under native condition, Blue Native-PAGE and Blue Native-PAGE/SDS-PAGE 2D analyses demonstrated co-existence of the α1 subunit and c-Src in same protein complex, as well as a direct interaction between the α1 subunit and c-Src. By comparison of cleavable and non-cleavable cysteine-cysteine crosslinked samples, capillary immunoblotting analysis demonstrated that depletion of Src kinase family members (c-Src, Yes, and Fyn) or cav-1 clearly reduced the interactions of the α1 subunit with proteins, but depletion of cav-1 did not affect the interaction of c-Src with the α1 subunit. The data indicated that there are direct interactions between the α1 subunit and c-Src as well as between the α1 subunit and cav-1, but argued about the interaction between c-Src and cav-1 under the condition. Furthermore, the data also indicated the existence of different protein complexes containing the α1 subunit and c-Src, which might have different signaling functions.

Metabolic Syndrome and Salt-Sensitive Hypertension in Polygenic Obese TALLYHO/JngJ Mice: Role of Na/K-ATPase Signaling.

We have demonstrated that Na/K-ATPase acts as a receptor for reactive oxygen species (ROS), regulating renal Na+ handling and blood pressure. TALLYHO/JngJ (TH) mice are believed to mimic the state of obesity in humans with a polygenic background of type 2 diabetes. This present work is to investigate the role of Na/K-ATPase signaling in TH mice, focusing on susceptibility to hypertension due to chronic excess salt ingestion. Age-matched male TH and the control C57BL/6J (B6) mice were fed either normal diet or high salt diet (HS: 2, 4, and 8% NaCl) to construct the renal function curve. Na/K-ATPase signaling including c-Src and ERK1/2 phosphorylation, as well as protein carbonylation (a commonly used marker for enhanced ROS production), were assessed in the kidney cortex tissues by Western blot. Urinary and plasma Na+ levels were measured by flame photometry. When compared to B6 mice, TH mice developed salt-sensitive hypertension and responded to a high salt diet with a significant rise in systolic blood pressure indicative of a blunted pressure-natriuresis relationship. These findings were evidenced by a decrease in total and fractional Na+ excretion and a right-shifted renal function curve with a reduced slope. This salt-sensitive hypertension correlated with changes in the Na/K-ATPase signaling. Specifically, Na/K-ATPase signaling was not able to be stimulated by HS due to the activated baseline protein carbonylation, phosphorylation of c-Src and ERK1/2. These findings support the emerging view that Na/K-ATPase signaling contributes to metabolic disease and suggest that malfunction of the Na/K-ATPase signaling may promote the development of salt-sensitive hypertension in obesity. The increased basal level of renal Na/K-ATPase-dependent redox signaling may be responsible for the development of salt-sensitive hypertension in polygenic obese TH mice.

A Mouse 5/6th Nephrectomy Model That Induces Experimental Uremic Cardiomyopathy.

Chronic kidney disease (CKD) is a great risk factor for cardiovascular disease events and mortality, and progressively develops to the clinical phenotype called "uremic cardiomyopathy". We describe here an experimental CKD mouse model, named 5/6th partial nephrectomy (PNx) with pole ligation, which developed uremic cardiomyopathy at four weeks post-surgery. This PNx model was performed by a two-step surgery. In step-one surgery, both poles of the left kidney were ligated. In step-two surgery, which was performed 7 days after the step-one surgery, the right kidney was removed. For the sham surgery, the same surgery procedures were performed but without pole ligation of the left kidney or removal of the right kidney. The surgical procedures are easier and less time-consuming, compared to other methods. However, the remnant functional renal mass is not as easily controlled as the renal artery ligation. Four weeks after surgery, in comparison with the sham-operated mice, the PNx mice developed impaired renal function, anemia, cardiac hypertrophy, cardiac fibrosis, and decreased heart systolic and diastolic function.

Protein Carbonylation of an Amino Acid Residue of the Na/K-ATPase α1 Subunit Determines Na/K-ATPase Signaling and Sodium Transport in Renal Proximal Tubular Cells.

BACKGROUND: We have demonstrated that cardiotonic steroids, such as ouabain, signaling through the Na/K-ATPase, regulate sodium reabsorption in the renal proximal tubule. By direct carbonylation modification of the Pro222 residue in the actuator (A) domain of pig Na/K-ATPase α1 subunit, reactive oxygen species are required for ouabain-stimulated Na/K-ATPase/c-Src signaling and subsequent regulation of active transepithelial (22)Na(+) transport. In the present study we sought to determine the functional role of Pro222 carbonylation in Na/K-ATPase signaling and sodium handling. METHODS AND RESULTS: Stable pig α1 knockdown LLC-PK1-originated PY-17 cells were rescued by expressing wild-type rat α1 and rat α1 with a single mutation of Pro224 (corresponding to pig Pro222) to Ala. This mutation does not affect ouabain-induced inhibition of Na/K-ATPase activity, but abolishes the effects of ouabain on Na/K-ATPase/c-Src signaling, protein carbonylation, Na/K-ATPase endocytosis, and active transepithelial (22)Na(+) transport. CONCLUSIONS: Direct carbonylation modification of Pro224 in the rat α1 subunit determines ouabain-mediated Na/K-ATPase signal transduction and subsequent regulation of renal proximal tubule sodium transport.

Prognostic Value of FDG PET/CT-Derived Parameters in Pancreatic Adenocarcinoma at Initial PET/CT Staging.

OBJECTIVE: The purpose of this study is to evaluate the performance of PET-derived parameters as prognostic markers for overall survival (OS) and progression-free survival (PFS) outcome in patients with pancreatic adenocarcinoma. MATERIALS AND METHODS: We conducted a retrospective study of 106 patients (62 men and 44 women) with histologically proven pancreatic adenocarcinoma who underwent initial staging FDG PET/CT before treatment. Peak standardized uptake value (SUV), maximum SUV (SUVmax), metabolic tumor volume, and tumor glycolytic activity of the primary pancreatic tumor were measured. Two segmentation methods were performed to obtain the metabolic tumor volume and tumor glycolytic activity for all tumors: a gradient-based segmentation model (metabolic tumor volume and tumor glycolytic activity by gradient edge detection) and a fixed-threshold model with a threshold of 50% of the lesion's SUVmax and peak SUV. Univariate and multivariate Cox regression models were developed including clinical and imaging parameters for OS and PFS. RESULTS: Multivariate Cox regression analysis showed a statistically significant association between PFS and age, SUVmax, peak SUV, and tumor glycolytic activity by gradient edge detection. There was a statistically significant difference in PFS for patients with values above and below the median cutoff points for SUVmax (hazard ratio [HR], 1.12; p < 0.01), peak SUV (HR, 1.25; p < 0.02), and tumor glycolytic activity measured by gradient edge detection (HR, 1.00; p < 0.02) of the primary tumor. However, multivariate Cox regression analysis showed a statistically significant association only between tumor glycolytic activity by gradient edge detection and OS (p = 0.04), and there was a statistically significant difference in OS between patients with values above and below the median cutoff point for the tumor glycolytic activity by gradient edge detection of the primary tumor (HR, 1.42; p = 0.05). CONCLUSION: Age, SUVmax, peak SUV, and total lesion glycolysis (i.e., tumor glycolytic activity) of the primary tumor are associated with PFS, and tumor glycolytic activity is associated with OS in patients with pancreatic adenocarcinoma.

Evaluation of osseous metastasis in bone scintigraphy.

Bone scintigraphy (BS) is an imaging tool commonly used for screening patients with cancer, especially those with high prevalence of osseous metastases including the breast, prostate, lung, thyroid, and kidney, which account for 80% of osseous metastasis. BS has been shown to be of value in the initial and subsequent treatment strategy of various malignancies. The purpose of this article is to evaluate the technical and imaging aspects of BS and to examine the present research into improved detection of osseous metastasis.

Use of the trellis device in the management of deep vein thrombosis: a retrospective single-center experience.

OBJECTIVES: The Trellis thrombectomy system (Covidien) is one of the newer devices that incorporates isolated pharmacomechanical thrombectomy and thrombolysis (PMT) for treatment of deep venous thrombosis (DVT). We conducted a retrospective review of patients with upper- and lower-extremity DVT managed with the Trellis thrombectomy system at our center. METHODS: All patients with symptomatic DVT who presented to our center between April 2010 and April 2011 who underwent PMT by the Trellis device were included in this retrospective review. RESULTS: Twenty-eight patients (mean age, 46.4 ± 21.2 years) presented with symptoms with a mean duration of 1.3 ± 1.8 months. Eighty-six percent had 100% occlusion on admission, while 14.3% had 70%-90% stenosis. The mean lytic dose used was tPA 20.7 ± 12 mg. The mean Trellis treatment time was 25.1 ± 11.5 minutes. Grade 3 lysis was achieved in 23 of 28 patients (85.8%), while grade 2 lysis was achieved in 14.2%. Mean total hospital stay was 2.6 ± 2.7 days. Postprocedure symptom resolution was 100%, and there was no reocclusion in 78.6% of patients at 1 year. At 12 months, the patency rate (primary or secondary) was 80% as determined by Doppler ultrasound. CONCLUSIONS: In patients with DVT involving the ilio-femoral and the upper-extremity vessels, the use of the Trellis device was associated with a high technical success rate as well as a satisfactory 12-month patency rate. Moreover, this strategy was associated with reduced lytic dose, shorter treatment time and hospital stay, and no bleeding complications.

The role of 18F-fluorodeoxyglucose positron emission tomography in the management of patients with pancreatic adenocarcinoma.

Pancreatic cancer continues to have a grim prognosis with 5-year survival rates at less than 5 %. It is a particularly challenging health problem given these poor survival outcomes, aggressive tumor biology, and late onset of symptoms. Most patients present with advanced unresectable cancer however, margin-negative resection provides a rare chance for cure for patients with resectable disease. The standard imaging modality for the diagnosis and management of pancreatic cancer is contrast-enhanced multidetector computed tomography. Remarkable advances in CT technology have led to improvements in the ability to detect small tumors and intricate vasculature involvement by the tumor, yet CT is still restricted to providing a morphological portrait of the tumor. Diagnosis can be challenging due to similar appearance of certain benign and malignant disease. Distant metastatic disease can be silent on CT leading to improper staging, and thus management, of certain patients. Furthermore, radiation-induced fibrosis and necrosis complicate assessment of treatment response by CT alone. F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) is becoming a prevalent tool employed by physicians to improve accuracy in these clinical scenarios. Malignant transformation causes a high metabolic activity of cancer cells. 18F-FDG-PET captures this functional activity of malignancies by capturing areas with high glucose utilization rates. Imaging function rather than morphological appearance, 18F-FDG-PET has a unique role in the management of oncology patients with the ability to detect regions of tumor involvement that may be silent on conventional imaging. Literature on the sensitivity and specificity of 18F-FDG-PET fails to reach a consensus, and improvements resulting in hybridization of 18F-FDG-PET and CT imaging techniques are preliminary. Here we review the potential role of 18F-FDG-PET and PET/CT in improving accuracy in the initial evaluation and subsequent steps in the management of pancreatic cancer patients.

Contrast enhanced computed tomography characterization of fluorodeoxygluocose-avid regional and non-regional lymph nodes in patients with suspicion of metastatic bladder cancer.

OBJECTIVE: The objective of this study is to assess if size alone can predict the presence of metastatic disease within lymph nodes seen on contrast enhanced-computed tomography (CE-CT) in patients with suspicion of metastatic bladder cancer and also to evaluate the nodal distribution and morphological characteristics of fluorodeoxygluocose (FDG) avid lymph nodes on CE-CT. MATERIALS AND METHODS: A retrospective analysis from 2002 to 2009 was performed on patients with suspicion of recurrent disease undergoing restaging FDG-positron emission tomography (PET)/CT. Standardized uptake value (SUVmax) adjusted for lean body mass was recorded in abnormal lymph nodes in the abdominopelvic region. Distribution, size, shape, presence of necrosis and clustering of the FDG-avid lymph nodes was assessed on CE-CT obtained within 4 weeks of the PET/CT. The abnormal nodes were then compared with non-FDG avid lymph nodes on the contralateral side serving as control. RESULTS: A total of 103 lymph nodes were found to be FDG-avid in 14 patients on 17 PET/CT examinations. Overall, mean SULmax was 4.7 (range: 1.6-10.7), which is significantly higher than background of 1.5 (P < 0.05). Regional pelvic lymph nodes were FDG-avid in 93% of patients and metastatic extra-pelvic in 100% of patients. The overall average size of the FDG avid lymph nodes on CE-CT was 11 mm with a third of these measuring 3-8 mm. The average size of FDG-avid lymph nodes was 11 mm in the paraaortic region 13 mm in the common iliac 9 mm in the internal iliac and 13 mm in the external iliac regions. Nearly 88.4% of lymph nodes were round in shape, clustering was present in 68% and necrosis in 7% and average size of lymph nodes that served as controls was 6 mm with reniform morphology in 92% and absence of clustering and necrosis. CONCLUSION: Overlap in size exists between FDG-avid pathological and non-pathological lymph nodes seen on CE-CT in patients with metastatic bladder cancer. Other characteristic such as abnormal morphology and clustering are useful adjuncts in the evaluation of nodal metastatic disease.

Inducibility of atrial fibrillation after GP ablations and "autonomic blockade": evidence for the pathophysiological role of the nonadrenergic and noncholinergic neurotransmitters.

BACKGROUND: Recent clinical reports that used cholinergic and adrenergic blockade (CAB) as an alternative to ganglionated plexi (GP) ablation to terminate atrial fibrillation (AF) showed mixed results. We investigated the role of other neurotransmitters in AF inducibility. METHODS: In 23 pentobarbital anesthetized dogs, a left and right thoracotomy allowed the attachment of electrode catheters to the left and right pulmonary veins and atrial appendages (AA). Programmed stimulation was used to determine the effective refractory periods (ERP) and AF inducibility, measured by the window of vulnerability (WOV). AF duration in response to acetylcholine (Ach; 100 mM) applied to the AA was measured before and after GP ablation + CAB and with vagus nerve stimulation (VNS). After GP ablation + CAB, Ach induced AF duration was determined in response to vasoactive intestinal peptide (VIP) and its specific antagonist ([Ac-Tyr1,D-phe2]-VIP). RESULTS: GP ablation + CAB significantly prolonged ERP, eliminated WOV, and suppressed the duration of Ach induced AF (P ≤ 0.01 for all). Also slowing of the heart rate by VNS was essentially blocked; however, with Ach 100 mM applied to the AA, VNS, and VIP applied to the AA markedly prolonged AF duration. This effect was blocked by the VIP antagonist. CONCLUSIONS: Neither GP ablation nor CAB can fully suppress AF inducibility arising from the atrial neural network. Our findings suggest that other neurotransmitters, such as VIP released during VNS, can promote sustained AF despite GP ablation and "autonomic blockade," which may further define the substrate for AF outside the pulmonary vein-atrial junctions.

Cardiac myxoma induced paraneoplastic syndromes: a review of the literature.

BACKGROUND: Atrial myxomas are the most common benign tumors of the heart and may present with a wide variety of symptoms. Although 45% of patients present with neurological symptoms, a diverse range of systemic symptoms also occur. METHODS: A systemic review of the literature related to the diagnosis, treatment, pathogenesis, and symptoms associated with atrial myxomas was performed. RESULTS: Here we summarize the current state of understanding about myxoma pathogenesis and treatments are described. We review the common and rare local and systemic effects of myxomas. Additionally, we review the paraneoplastic and metastatic potential of myxomas. CONCLUSIONS: A better understanding of the diverse disease presentations, paraneoplastic syndromes, and side effects of cytokine abnormalities stemming from myxomas will aid the physician in earlier detection and monitoring of disease recurrence.

FT-IR microspectroscopy of mouse colon tissues: insight into the chemistry of carcinogenesis and diagnostic potential.

We studied colon carcinogenesis using Fourier-transform infrared (FT-IR) microspectroscopy, an evolving method that allows the nondestructive assessment of the chemical composition of cells and tissues and of the in situ relationship between molecules, and assessed its diagnostic potential. Mid-FT-IR spectra were obtained from frozen colon tissue samples of normal (C57BL/6J) and Min (Apc(Min) mutant) mice, the latter recapitulating key features of human colon carcinogenesis. Classic spectroscopic analysis demonstrated marked differences in the Mid-FT-IR spectra between normal and dysplastic tissues, especially regarding peak positions and band intensity ratios in the regions 1800 to 985 cm(-1) and 3000 to 2700 cm(-1), reflecting changes in cellular nucleic acids, phosphates, and carbohydrates. Analysis of the spectra using the multivariate methods backpropagation neural networks, decision tree, adaboost with decision tree, and support vector machine, which interrogated the intrinsic dimensionality of IR spectra, revealed that their sensitivity was between 91.1% and 100% and their specificity between 94.1% and 100%, with the outcomes of the Support Vector Machine algorithm being identical to those of histologic analysis. FT-IR microspectroscopy holds great promise not only as a method of ascertaining changes in the chemistry of the neoplastic cells but also as a diagnostic tool, especially for early stages of carcinogenesis not detectable by other means.

Noise considerations for PET quantification using maximum and peak standardized uptake value.

UNLABELLED: In tumor response monitoring studies with (18)F-FDG PET, maximum standardized uptake value (SUV(max)) is commonly applied as a quantitative metric. Although it has several advantages due to its simplicity of determination, concerns about the influence of image noise on single-pixel SUV(max) persist. In this study, we measured aspects of bias and reproducibility associated with SUV(max) and the closely related peak SUV (SUV(peak)) using real patient data to provide a realistic noise context. METHODS: List-mode 3-dimensional PET data were acquired for 15 min over a single bed position in twenty (18)F-FDG oncology patients. For each patient, data were sorted so as to form 2 sets of images: respiration-gated images such that each image had statistical quality comparable to a 3 min/bed position scan, and 5 statistically independent (ungated) images of different durations (1, 2, 3, 4, and 5 min). Tumor SUV(max) and SUV(peak) (12-mm-diameter spheric region of interest positioned so as to maximize the enclosed average) were analyzed in terms of reproducibility and bias. The component of reproducibility due to statistical noise (independent of physiologic and other variables) was measured using paired SUVs from 2 comparable respiration-gated images. Bias was measured as a function of scan duration. RESULTS: Replicate tumor SUV measurements had a within-patient SD of 5.6% ± 0.9% for SUV(max) and 2.5% ± 0.4% for SUV(peak). SUV(max) had average positive biases of 30%, 18%, 12%, 4%, and 5% for the 1-, 2-, 3-, 4-, and 5-min images, respectively. SUV(peak) was also biased but to a lesser extent: 11%, 8%, 5%, 1%, and 4% for the 1-, 2-, 3-, 4-, and 5-min images, respectively. CONCLUSION: The advantages of SUV(max) are best exploited when PET images have a high statistical quality. For images with noise properties typically associated with clinical whole-body studies, SUV(peak) provides a slightly more robust alternative for assessing the most metabolically active region of tumor.

A phase I trial of erlotinib and concurrent chemoradiotherapy for stage III and IV (M0) squamous cell carcinoma of the head and neck.

PURPOSE: Erlotinib, an orally active selective inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase, has synergistic activity with radiation and with cisplatin. The EGFR is overexpressed in the majority of head and neck cancers. The primary objective of this phase I study was to determine the maximum-tolerated dose (MTD) of erlotinib in combination with low-dose daily cisplatin and radiotherapy. We also sought evidence of biologic activity of erlotinib alone using serial 18-FDG positron emission tomography (PET) imaging. EXPERIMENTAL DESIGN: Oral erlotinib was taken daily starting with a 14-day run-in and continued until radiation therapy (RT) was completed. Low-dose daily cisplatin, 6 mg/m(2) i.v. was given concurrently with standard fractionation RT to a total dose of 66 to 70 Gy. Dose escalation followed a modified Fibonacci dose escalation design. RESULTS: Twenty-two patients were enrolled and 18 patients received therapy on protocol. MTD of the combination of erlotinib, cisplatin, and RT was not reached. The recommended phase II dose of erlotinib is 150 mg per day in combination with cisplatin and RT, the highest dose of erlotinib evaluated in this study. 18F-FDG PET showed evidence for metabolic response to single-agent erlotinib. Per PERCIST criteria, the overall metabolic response rate at day 14 was 38.8% (95% CI: 17.3-64.3). On completion of concurrent chemoradiotherapy, overall response rate derived from tumor measurements based on imaging studies was 83% for all dose levels combined. CONCLUSIONS: Erlotinib in combination with low-dose daily cisplatin and RT is well tolerated and shows evidence of clinical efficacy. The combination should be evaluated further.

Atrial myxoma and bone changes: a paraneoplastic syndrome?

Atrial myxomas are the most common benign tumors of the heart and are difficult to diagnose due to a wide variety of presenting symptoms. We present a patient with a five-year history of visual loss, vertigo, ataxia, tinnitus, and bone lesions that resolved after diagnosis and resection of an atrial myxoma. This case not only highlights an unusual presentation of atrial myxomas but also raises the question of whether atrial myxomas can produce paraneoplastic syndromes, including bone abnormalities.

The role of PET scanning in pancreatic cancer.

The strength of functional imaging lies in its ability to detect malignant disease irrespective of lesion morphology. In this setting, 18FDG-PET can complement management by providing a more accurate diagnosis. When combined as an adjunct to CT, 18FDG-PET can increase the sensitivity, specificity, and accuracy for detecting a pancreatic malignancy, especially in patients in whom CT alone fails to identify a discrete mass or in whom biopsy results are indeterminate. This capability is accentuated with small lesions of the pancreas. 18FDG-PET is significantly more sensitive in detecting metastatic disease than conventional CT imaging. Moreover, 18FDG-PET is able to differentiate tumor response to therapy in the postoperative setting, and could potentially serve to monitor recurrence patterns in the setting of neoadjuvant or adjuvant chemoradiotherapy. Finally, as 18FDG-PET/CT fusion modalities become more widespread and technical advances in image acquisition progress, 18FDG-PET will continue to have an increasing role in the diagnosis, staging, and surveillance of pancreatic cancer, integrating anatomic information with functional imaging.

Characterization of a perirectal artifact in 18F-FDG PET/CT.

UNLABELLED: Assessing tumor involvement in the rectal region can sometimes be complicated by what appears to be an artifact on (18)F-FDG PET/CT images. This artifact manifests as a high-intensity region on the PET image, extending posterior to the bladder in the area around the rectum. The aim of this study was to describe this artifact, which-as far as we are aware-has not been previously reported, and to investigate its cause. METHODS: One hundred (18)F-FDG PET/CT studies (ordered-subsets expectation maximization reconstruction, CT attenuation correction) of patients with no known malignancy in the pelvis were retrospectively reviewed. Localized regions of apparently high uptake posterior to the bladder were considered an artifact when there was a discrepancy between attenuation-corrected (asymmetric appearance) and non-attenuation-corrected images (symmetric appearance). In addition, an experiment was performed using a body phantom containing 2 cylindric inserts simulating the bladder and a region of low-attenuation rectal gas. Attenuation-corrected images were reconstructed with different amounts of spatial misregistration intentionally introduced between the CT and PET images. RESULTS: The artifact was observed in 15 of 100 patient studies and had a mean maximum standardized uptake value of 4.8 ± 2.7. When fused with sequentially acquired CT images, the artifact always appeared to be in the perirectal region near the bladder and an area of rectal gas. The phantom study indicated this artifact was consistent with an attenuation-correction problem caused by misregistration between CT and PET. Movement of gas within the rectum can cause an air pocket to be present during the PET acquisition at a location where CT indicated soft tissue. The resulting localized overcorrection for attenuation at the margin of the rectum and the extremely high activity concentration in the nearby bladder contributed to the artifact. CONCLUSION: Movement of gas within the rectum between acquisition of CT and PET images can lead to an artifact in attenuation-corrected PET images in the perirectal region. An awareness of this artifact and reference to non-attenuation-corrected images will aid in the interpretation of (18)F-FDG pelvis studies.

Tumor necrosis factor-alpha-induced changes in insulin-producing beta-cells.

The migration of macrophages and lymphocytes that produce cytokines such as tumor necrosis factor-alpha (TNF-alpha) causes beta-cell death, leading to type 1 diabetes. Similarly, in type 2 diabetes, the adipocyte-derived cytokines including TNF-alpha are elevated in the circulation, causing inflammation and insulin resistance. Thus, the studies described in this article using TNF-alpha are relevant to furthering our understanding of the pathogenesis of diabetes mellitus. We used RINr1046-38 (RIN) insulin-producing beta-cells, which constitutively express calbindin-D(28k), to characterize the effect of TNF-alpha on apoptosis, replication, insulin release, and gene and protein expression. Western blots of TNF-alpha-treated RIN cells revealed a decrease in calbindin-D(28k). By ELISA, TNF-alpha-treated beta-cells had 47% less calbindin-D(28k) than controls. In association with the decline in calbindin-D(28k), TNF-alpha treatment of RIN cells led to a 73% greater increase in changes in intracellular calcium concentration (Delta[Ca(2+)](i)) in TNF-alpha-treated cells as compared to that in control RIN cells upon treatment with 50 mM KCl; caused a greater increase in the [Ca(2+)](i) following the addition of 5.5 microM ionomycin; increased by more than threefold the apoptotic rate, expressed as the percentage of TUNEL-positive nuclei to total nuclei; decreased the rate of cell replication by 36%; and increased and decreased selectively the expression of specific genes as determined by microarray analysis. The subcellular localizations of Bcl-2, an antiapoptotic protein, and Bax, a proapoptotic protein, within RIN cells were altered with TNF-alpha treatment such that the two were colocalized with mitochondria in the perinuclear region. We conclude that the proapoptotic action of TNF-alpha on beta-cells is manifested via decreased expression of calbindin-D(28k) and is mediated at least in part by [Ca(2+)](i).