Saila Kauhanen

A prospective diagnostic accuracy study of 18F-fluorodeoxyglucose positron emission tomography/computed tomography, multidetector row computed tomography, and magnetic resonance imaging in primary diagnosis and staging of pancreatic cancer.

Objective:To prospectively compare the accuracy of combined positron emission tomography/computed tomography using 18F-fluorodeoxyglucose (FDG-PET/CT), multidetector row computed tomography (MDCT), and magnetic resonance imaging (MRI) in the evaluation of patients with suspected pancreatic malignancy. Summary Background Data:FDG-PET/CT imaging is increasingly used for staging of pancreatic cancer. Preliminary data suggest a significant influence of FDG-PET/CT on treatment planning, although its role is still evolving. Methods:Thirty-eight consecutive patients with suspicion of pancreatic malignancy were enrolled. Patients underwent a protocol including FDG-PET/CT, MDCT, and MRI combined with magnetic resonance cholangiopancreatography, all of which were blindly evaluated. The findings were confirmed macroscopically at operation and/or by histopathologic analysis (n = 29) or follow-up (n = 9). Results of TNM classification of different imaging methods were compared with clinical TNM classification. Results:Pancreatic adenocarcinoma was diagnosed in 17 patients, neuroendocrine tumor in 3, mass-forming pancreatitis in 4, cystic lesion in 6, and fibrosis in 2. Six patients had a finding of a normal pancreas. The diagnostic accuracy of FDG-PET/CT for pancreatic malignancy was 89%, compared with 76% and 79% for MDCT and MRI, respectively. In the differential diagnosis of suspected malignant biliary stricture at endoscopic retrograde cholangiopancreaticography (n = 21), FDG-PET/CT had a positive predictive value of 92%. In 17 patients with advanced pancreatic adenocarcinoma, FDG-PET/CT had a sensitivity of 30% for N- and 88% for M-staging. Both MDCT and MRI had sensitivities of 30% for N- and 38% for M-staging. Furthermore, the clinical management of 10 patients (26%) was altered after FDG-PET/CT. Conclusion:FDG-PET/CT was more sensitive than conventional imaging in the diagnosis of both primary pancreatic adenocarcinoma and associated distant metastases. In contrast, the sensitivity of FDG-PET/CT was poor in detecting local lymph node metastasis, which would have been important for an assessment of resectability. We recommend the use of FDG-PET/CT in the evaluation of diagnostically challenging cases, especially in patients with biliary strictures without evidence of malignancy in conventional imaging.

Decreased Blood Flow with Increased Metabolic Activity: A Novel Sign of Pancreatic Tumor Aggressiveness

Purpose: To study blood flow (BF) and metabolism in normal pancreas and in different pancreatic lesions. We then determined the effect of these biomarkers on outcome in patients with pancreatic cancer. Experimental Design: Oxygen-15–labeled water and fluorodeoxyglucose positron emission tomography/computed tomography scans were used in 26 patients with a suspicion of pancreatic cancer to measure pancreatic BF and metabolism. In addition, the ratio of standardized uptake value to BF (SUV/BF) was calculated. Patients were divided into three groups: patients with a finding of normal pancreas (n = 7), benign lesions (n = 8), and malignant tumors (n = 11). Results: Patients with benign and malignant pancreatic tumors had decreased BF of the lesion by 48% and 60%, respectively, compared with patients with normal pancreatic tissue. SUVmax was 3-fold higher in malignant tumors compared with both benign lesions and normal pancreas (P < 0.05). In contrast, the SUVmax of patients with benign lesions and normal pancreas did not differ. The SUV/BF ratio was significantly higher in malignant lesions than in benign lesions or in patients with normal pancreas (P < 0.05). In patients with cancer, high SUV/BF ratio was a stronger predictor of poor survival compared with high metabolism or lower-than-normal pancreatic BF. Conclusions: BF in pancreatic cancer is significantly reduced compared with the normal pancreas, which may in part explain the poor success of both radiotherapy and chemotherapy. We suggest that the composite measurement of BF and metabolism in pancreatic cancer could serve as a novel tool in the planning of treatments targeting vasculature. (Clin Cancer Res 2009;15(17):5511–7)

The clinical value of [18F]-fluoro-dihydroxyphenylalanine positron emission tomography in primary diagnosis, staging and restaging of neuroendocrine tumors

The study was set up to determine the clinical value of dihydroxyphenylalanine positron emission tomography-computed tomography ([(18)F]DOPA PET-CT) in patients with neuroendocrine tumors (NETs). Eighty-two patients with suspected/known NET were imaged with PET(-CT) using [(18)F]DOPA. Patients were divided into two groups: primary diagnosis/staging and restaging of disease. All patients without previous diagnosis of NET had biochemical proof of disease. The diagnostic accuracy of PET was assessed by comparing the histopathology and clinical follow-up. The overall accuracy of [(18)F]DOPA PET was 90%. In patients having PET for primary diagnosis/staging (n=32), the accuracy of PET was 88%, and for restaging 92% (n=61). The mean s.d. sizes of primary and metastatic lesions detected by PET were 26+/-11 and 16+/-9 mm respectively. In organ-region-specific analysis, the sensitivity and specificity were 100% in the primary diagnosis of pheochromocytoma (n=16) and metastases were found in all cases with recurrent disease (n=5). The accuracy for NET of gastrointestinal tract was 92% in restaging (n=24). For the NETs located in the head-neck-thoracic region (n=19), the overall accuracy of PET was 89% including 12 cases of recurrent medullary thyroid cancer with a sensitivity of 90%. In analysis of patients with biochemical proof of disease combined with negative conventional imaging methods, PET had positive and negative predictive value of 92% and 95% respectively. [(18)F]DOPA PET-CT provided important additional information in the diagnosis of pheochromocytoma and restaging of known NET. Both in primary diagnosis and in patients with formerly known NET and increasing tumor markers, [(18)F]DOPA PET-CT is a sensitive first-line imaging method.

Complicated intra-abdominal infections in Europe: a comprehensive review of the CIAO study

The CIAO Study (“C omplicated Intra-A bdominal infection O bservational” Study) is a multicenter investigation performed in 68 medical institutions throughout Europe over the course of a 6-month observational period (January-June 2012).Patients with either community-acquired or healthcare-associated complicated intra-abdominal infections (IAIs) were included in the study.2,152 patients with a mean age of 53.8 years (range: 4–98 years) were enrolled in the study. 46.3% of the patients were women and 53.7% were men. Intraperitoneal specimens were collected from 62.2% of the enrolled patients, and from these samples, a variety of microorganisms were collectively identified.The overall mortality rate was 7.5% (163/2.152).According to multivariate analysis of the compiled data, several criteria were found to be independent variables predictive of patient mortality, including patient age, the presence of an intestinal non-appendicular source of infection (colonic non-diverticular perforation, complicated diverticulitis, small bowel perforation), a delayed initial intervention (a delay exceeding 24 hours), sepsis and septic shock in the immediate post-operative period, and ICU admission.Given the sweeping geographical distribution of the participating medical centers, the CIAO Study gives an accurate description of the epidemiological, clinical, microbiological, and treatment profiles of complicated intra-abdominal infections (IAIs) throughout Europe.

Complementary Roles of 18F-DOPA PET/CT and 18F-FDG PET/CT in Medullary Thyroid Cancer

Serum calcitonin and carcinoembryonic antigen (CEA) are markers of recurrent or persistent disease in medullary thyroid cancer (MTC). However, conventional imaging often fails to localize metastatic disease. Our aim was to compare fluorine-labeled dihydroxyphenylalanine (18F-DOPA) and 18F-FDG PET/CT with multidetector CT (MDCT) and MRI in recurrent or persistent MTC. Methods: Nineteen MTC patients with increased calcitonin or CEA on follow-up (mean ± SD, 93 ± 91 mo; range, 4–300 mo) after primary therapy were prospectively imaged with 4 techniques: 18F-DOPA PET/CT, 18F-FDG PET/CT, MDCT, and MRI. Images were analyzed for pathologic lesions, which were surgically removed when possible. The correlation between the detection rate for each method and the calcitonin and CEA concentrations and histopathologic findings was investigated. Results: On the basis of histology and follow-up, one or more imaging methods accurately localized metastatic disease in 12 (63%) of 19 patients. The corresponding figures for 18F-DOPA PET/CT, 18F-FDG PET/CT, MDCT, and MRI were 11 (58%) of 19, 10 (53%) of 19, 9 (47%) of 19, and 10 (59%) of 17, respectively. Calcitonin and CEA correlated with 18F-DOPA PET/CT (P = 0.0007 and P = 0.0263, respectively) and 18F-FDG PET/CT findings (both P < 0.0001). In patients with an unstable calcitonin doubling time (n = 8), 18F-DOPA and 18F-FDG PET/CT were equally sensitive. In contrast, for patients with an unstable CEA doubling time (n = 4), 18F-FDG PET/CT was more accurate. Conclusion: For most MTC patients with occult disease, 18F-DOPA PET/CT accurately detects metastases. In patients with an unstable calcitonin level, 18F-DOPA PET/CT and 18F-FDG PET/CT are complementary. For patients with an unstable CEA doubling time, 18F-FDG PET/CT may be more feasible. MRI is sensitive but has the highest rate of false-positive results.

Premedication With Carbidopa Masks Positive Finding of Insulinoma and β-Cell Hyperplasia in [18F]-Dihydroxy-Phenyl-Alanine Positron Emission Tomography

TO THE EDITOR: We read with interest the excellent and valuable article by Koopmans and colleagues concerning staging of carcinoid and islet cell tumors with [F]-dihydroxy-phenyl-alanine (FDOPA) and [C]-5-hydroxy-tryptophan (C-5-HTP) positron emission tomography/computed tomography (PET-CT). They reported that PET-CT using C-5-HTP as a tracer is a more sensitive method in the diagnosis of islet cell tumors compared with PET-CT using tracer F-DOPA (96% v 80%). However, we would like to raise concerns regarding that study’s use of carbidopa pretreatment before F-DOPA PET scanning in patients suspected of having islet cell tumor of the pancreas. We and others have recently shown that when studied without carbidopa pretreatment, F-DOPA PET is a highly sensitive method for localization of focal -cell hyperplasia in infants and insulinoma and -cell hyperplasia in adults. We are currently carrying out a prospective study to test the effect of carbidopa on pancreatic FDOPA uptake in patients with suspected islet cell tumor. So far, three consecutive patients have undergone F-DOPA PET-CT, both with and without premedication, and all have histological confirmation of the disease. Characteristics of the patients, the findings of different imaging methods, and histopathological data are shown in Table 1. In two out of three patients, insulinoma and -cell hyperplasia were observed in F-DOPA PET without carbidopa premedication but were fully masked when decarboxylation was prevented by carbidopa (Fig 1). In one study patient with insulinoma, both PET scans showed the lesions. The phenomenon behind this might be explained by the metabolites of F-DOPA. Oral premedication with carbidopa, an inhibitor of amino acid decarboxylase, improves the contrast in PET imaging by increasing the concentration and availability of F-DOPA and 3-Omethyl-6-[F]-fluoro-L-dopa and by reducing urinary radioactivity concentration. It has become a standard procedure in visualization of neuroendocrine tumors (NETs). A few studies have shown that the image quality improves markedly after pretreatment with carbidopa, as a result of equivalent metabolic pathways. In addition to the 6-fluorodopamine metabolite, F-DOPA is also the origin of many other metabolites such as 3-O-methyl-6[F]-fluoro-L-dopa, 6-fluoro-L-3,4-dihydroxyphenylacetic acid, and 6-fluorohomovanillic acid, as well as sulfated conjugates. When the amino acid decarboxylase pathway is blocked with carbidopa, the amount of metabolites changes. So far, the accumulation of these metabolites other than 6-fluorodopamine into various types of NETs is largely unknown. In conclusion, prevention of F-DOPA decarboxylation by means of carbidopa premedication totally prohibited accumulation of radioactivity into the disease focus in two out of three patients with histologically proven insulinoma and -cell hyperplasia. Our report is the first to demonstrate that imaging of islet cell tumors using PET and labeled amino acid precursors differs from imaging of other NETs. Therefore our recommendation is that until larger studies are available, carbidopa should not be given in F-DOPA PET imaging when islet cell tumor is suspected.

Accuracy of 18F-FDG PET/CT, Multidetector CT, and MR Imaging in the Diagnosis of Pancreatic Cysts: A Prospective Single-Center Study

Accurate diagnosis of the nature of pancreatic cysts is challenging but more important than ever, in part because of the increasing number of incidental cystic findings in the pancreas. Preliminary data suggest that 18F-FDG PET/CT may have a significant influence on clinical decision making, although its role is still evolving. Our aim was to prospectively compare the accuracy of combined 18F-FDG PET and contrast-enhanced CT (18F-FDG PET/CT), multidetector CT (MDCT), and MR imaging in differentiating malignant from benign pancreatic cysts. Methods: Thirty-one consecutive patients with pancreatic cysts were enrolled in the study. They underwent a protocol including 18F-FDG PET/CT, MDCT, and MR imaging combined with MR cholangiopancreatography, all of which were evaluated in a masked manner. The findings were confirmed macroscopically at surgery or histopathologic analysis (n = 22) or at follow-up (n = 9). Results: Of the 31 patients, 6 had malignant and 25 had benign lesions. The diagnostic accuracy was 94% for 18F-FDG PET/CT, compared with 77% and 87% for MDCT (P < 0.05) and MR imaging, respectively. 18F-FDG PET/CT had a negative predictive value of 100% and a positive predictive value of 75% for pancreatic cysts. The maximum standardized uptake value was significantly higher in malignant (7.4 ± 2.6) than in benign lesions (2.4 ± 0.8) (P < 0.05). When the maximum standardized uptake value was set at 3.6, the sensitivity and specificity were 100% and 88%, respectively. Furthermore, when compared with MDCT and MR imaging, respectively, 18F-FDG PET/CT altered the clinical management of 5 and 3 patients, respectively. Conclusion: 18F-FDG PET/CT is an accurate imaging modality for differentiating between benign and malignant pancreatic cysts. We recommend the use of 18F-FDG PET/CT in the evaluation of diagnostically challenging pancreatic cysts.

Complicated intra-abdominal infections in Europe: preliminary data from the first three months of the CIAO Study

The CIAO Study is a multicenter observational study currently underway in 66 European medical institutions over the course of a six-month study period (January-June 2012).This preliminary report overviews the findings of the first half of the study, which includes all data from the first three months of the six-month study period.Patients with either community-acquired or healthcare-associated complicated intra-abdominal infections (IAIs) were included in the study.912 patients with a mean age of 54.4 years (range 4–98) were enrolled in the study during the first three-month period. 47.7% of the patients were women and 52.3% were men. Among these patients, 83.3% were affected by community-acquired IAIs while the remaining 16.7% presented with healthcare-associated infections. Intraperitoneal specimens were collected from 64.2% of the enrolled patients, and from these samples, 825 microorganisms were collectively identified.The overall mortality rate was 6.4% (58/912). According to univariate statistical analysis of the data, critical clinical condition of the patient upon hospital admission (defined by severe sepsis and septic shock) as well as healthcare-associated infections, non-appendicular origin, generalized peritonitis, and serious comorbidities such as malignancy and severe cardiovascular disease were all significant risk factors for patient mortality.White Blood Cell counts (WBCs) greater than 12,000 or less than 4,000 and core body temperatures exceeding 38°C or less than 36°C by the third post-operative day were statistically significant indicators of patient mortality.

18F-Fluorodihydroxyphenylalanine in the Diagnosis of Neuroendocrine Tumors

(18)F-fluorodihydroxyphenylalanine (FDOPA) is a powerful tool for the diagnosis and detection of neuroendocrine tumors when planning and monitoring surgical and oncologic therapies. Pheochromocytomas, paragangliomas, and medullary thyroid cancers especially are amenable to FDOPA imaging because of the high specific uptake of this amino acid analogue and excellent tumor-to-background contrast on PET/computed tomography.

Effects of meal and incretins in the regulation of splanchnic blood flow

Objective Meal ingestion is followed by a redistribution of blood flow (BF) within the splanchnic region contributing to nutrient absorption, insulin secretion and glucose disposal, but factors regulating this phenomenon in humans are poorly known. The aim of the present study was to evaluate the organ-specific changes in BF during a mixed-meal and incretin infusions. Design A non-randomized intervention study of 10 healthy adults to study splanchnic BF regulation was performed. Methods Effects of glucose-dependent insulinotrophic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) infusions and mixed-meal were tested in 10 healthy, glucose tolerant subjects using PET-MRI multimodal imaging technology. Intestinal and pancreatic BF and blood volume (BV) were measured with 15O-water and 15O-carbon monoxide, respectively. Results Ingestion of a mixed-meal led to an increase in pancreatic and jejunal BF, whereas duodenal BF was unchanged. Infusion of GIP and GLP-1 reduced BF in the pancreas. However, GIP infusion doubled blood flow in the jejunum with no effect of GLP-1. Conclusion Together, our data suggest that meal ingestion leads to increases in pancreatic BF accompanied by a GIP-mediated increase in jejunal but not duodenal blood flow.