Diagnostic performance of a computer-assisted diagnostic system: sensitivity of BONENAVI for bone scintigraphy in patients with disseminated skeletal metastasis is not so high.

PURPOSE: Bone scintigraphy (BS) of disseminated skeletal metastasis is sometimes misinterpreted as normal. The use of computer-assisted diagnosis (CAD) may resolve this problem. We investigated the performance of a CAD system, BONENAVI, in the diagnosis of disseminated skeletal metastasis. METHODS: Cases of disseminated skeletal metastasis were selected from a BS log. These patients' BSs were analyzed by BONENAVI to obtain an artificial neural network (ANN) and bone scan index (BSI). Clinical features (type of primary cancer, CT type, and BS type) were compared with the BONENAVI (ANN and BSI) results. The BS findings (diffuse increased axial skeleton uptake, inhomogeneity of uptake, proximal extremity contrast, and degree of renal uptake) and ANN or BSI were evaluated. Then, negative ANN patients were presented. RESULTS: Fifty-four patients were diagnosed as having disseminated skeletal metastasis. Regarding the primary cancers, 12 had prostate cancer, 16 gastric cancers, 16 breast cancers, and 10 miscellaneous cancers. Total sensitivity of ANN (≥ 0.5) was 76% (41/54). ANN values correlated with the BS type among clinical features. Diffuse increased axial skeleton uptake was mostly correlated with ANN of the BS findings. CONCLUSION: The BONENAVI CAD system was partially helpful in diagnosing disseminated skeletal metastasis, but the sensitivity of BONENAVI was not sufficient and underestimated the disseminated skeletal metastasis. Further improvement of this CAD system is necessary to improve the detectability of disseminated skeletal metastasis.

Anti-connective tissue growth factor (CTGF/CCN2) monoclonal antibody attenuates skin fibrosis in mice models of systemic sclerosis.

BACKGROUND: Systemic sclerosis (SSc) is characterized by fibrosis of the skin and internal organs. Although the involvement of connective tissue growth factor (CTGF/CCN2) has been well-documented in SSc fibrosis, the therapeutic potential of targeting CTGF in SSc has not been fully investigated. Our aim was to examine the therapeutic potential of CTGF blockade in a preclinical model of SSc using two approaches: smooth muscle cell fibroblast-specific deletion of CTGF (CTGF knockout (KO)) or a human anti-CTGF monoclonal antibody, FG-3019. METHODS: Angiotensin II (Ang II) was administered for 14 days by subcutaneous osmotic pump to CTGF KO or C57BL/6 J mice. FG-3019 was administered intraperitoneally three times per week for 2 weeks. Skin fibrosis was evaluated by histology and hydroxyproline assay. Immunohistochemistry staining was used for alpha smooth muscle actin (αSMA), platelet-derived growth factor receptor ß (PDGFRß), pSmad2, CD45, von Willebrand factor (vWF), and immunofluorescence staining was utilized for procollagen and Fsp1. RESULTS: Ang II-induced skin fibrosis was mitigated in both CTGF KO and FG-3019-treated mice. The blockade of CTGF reduced the number of cells expressing PDGFRß, procollagen, αSMA, pSmad2, CD45, and Fsp1 in the dermis. In addition, inhibition of CTGF attenuated vascular injury as measured by the presence of vWF-positive cells. CONCLUSIONS: Our data indicate that inhibition of CTGF signaling presents an attractive therapeutic approach in SSc.

Blockade of PDGF Receptors by Crenolanib Has Therapeutic Effect in Patient Fibroblasts and in Preclinical Models of Systemic Sclerosis.

Systemic sclerosis (SSc) is a multi-organ fibrotic disease with few treatment options. Activated fibroblasts are the key effector cells in SSc responsible for the excessive production of collagen and the development of fibrosis. Platelet-derived growth factor (PDGF), a potent mitogen for cells of mesenchymal origin, has been implicated in the activation of SSc fibroblasts. Our aim was to examine the therapeutic potential of crenolanib, an inhibitor of PDGF receptor signaling, in cultured fibroblasts and in angiotensin II-induced skin and heart fibrosis. Crenolanib effectively inhibited proliferation and migration of SSc and healthy control fibroblasts and attenuated basal and transforming growth factor-ß-induced expression of CCN2/CTGF and periostin. In contrast to healthy control fibroblasts, SSc fibroblasts proliferated in response to PDGFAA, whereas a combination of PDGFAA and CCN2 was required to elicit a similar response in healthy control fibroblasts. PDGF receptor α mRNA correlated with CCN2 and other fibrotic markers in the skin of SSc patients. In mice challenged with angiotensin II, PDGF receptor α-positive cells were increased in the skin and heart. These PDGF receptor α-positive cells co-localized with PDGF receptor ß, procollagen, and periostin. Treatment with crenolanib attenuated the skin and heart fibrosis. Our data indicate that inhibition of PDGF signaling presents an attractive therapeutic approach for SSc.

Evaluation of a computer-assisted diagnosis system, BONENAVI version 2, for bone scintigraphy in cancer patients in a routine clinical setting.

OBJECTIVE: To evaluate a computer-assisted diagnosis system, BONEVAVI version 2 for bone scintigraphy, this study examined the performance of the software in patients with and without skeletal metastasis. METHODS: Bone scans of various patients were analyzed by BONENAVI version 2. Patients with skeletal metastasis from prostate cancer, lung cancer, breast cancer, and other cancers were included in the study as true positive cases. Patients with normal bone scans, consecutive patients with several days of no skeletal metastasis (regardless of hot spots), and patients with abnormal bone scans but no skeletal metastasis were included as negative cases. Patient artificial neural network (ANN) values equal to or above 0.5 were regarded as positive, and those below 0.5 as negative. This study also analyzed cases according to primary cancer factors, osseous metastasis type, and bone tumor burden. RESULTS: The sensitivity of patient ANN values was 121/142 (85 %) for all cancers, 25/29 (86 %) for prostate cancer, 35/40 (88 %) for lung cancer, 37/45 (82 %) for breast cancer, and 24/28 (86 %) for other cancers. The specificity of ANN values was 40/49 (82 %) for normal bone scans, 99/122 (81 %) for consecutive patients with several days of no skeletal metastasis, and 44/81 (54 %) for patients with abnormal bone scans but no skeletal metastasis. Patients showing false negatives included: 10 patients with small lesions (6 of whom showed positive lesion ANN values), 4 patients with osteolytic lesions, 5 patients with intertrabecular osseous metastasis, and 1 patient with a metastatic lesion adjacent to the urinary bladder. The correlation between manually counted lesion numbers and Bone Scan Index was excellent for prostate cancer, and was good for lung cancer, breast cancer, and other cancers. CONCLUSION: BONENAVI version 2 is an effective computer-assisted diagnosis system for bone scanning, but the drawbacks of bone scanning remain unresolved.

Can dual-time-point 18F-FDG PET/CT differentiate malignant salivary gland tumors from benign tumors?

OBJECTIVE: The purpose of this study is to evaluate the usefulness of dual-time-point 18F-FDG PET/CT for discriminating between benign and malignant salivary gland tumors. MATERIALS AND METHODS: Dual-time-point FDG PET/CT images of 40 salivary gland tumors (20 benign and 20 malignant) were evaluated retrospectively. The maximum standardized uptake values (SUVmax) in the early and delayed phases and the retention index of each tumor were calculated and compared between benign and malignant tumors by the Mann-Whitney U test. Receiver operating characteristic (ROC) analysis was used to determine the diagnostic accuracy for malignant salivary gland tumors. The correlation between the delayed SUVmax and retention index was analyzed by calculation of the Spearman correlation coefficient. RESULTS: There were no significant differences in the mean early phase SUVmax or mean delayed phase SUVmax between benign and malignant tumors. The mean (±SD) retention index of the malignant tumors was significantly higher than that of the benign tumors (20.1%±10.2% vs 8.5%±12.3%; p=0.006). When the cutoff value of retention index (15.0%) was used, the sensitivity, specificity, and accuracy each was determined to be 75.0%. ROC analysis did not reveal a significant difference in the diagnostic accuracy between the delayed phase SUVmax and retention index (p=0.139). A significant correlation between the delayed phase SUVmax and retention index was observed for the benign salivary gland tumors (r=0.839; p<0.001). CONCLUSION: Dual-time-point FDG PET/CT is not useful for discriminating between benign and malignant salivary gland tumors, because benign tumors also show high FDG uptake, which increases in the delayed phase.

FDG PET/CT of a benign ovarian Brenner tumor.

We present a case of an ovarian benign Brenner tumor identified in an 85-year-old woman. During an observation period of over 1 year, the tumor increased in size and showed newly appeared solid component. Magnetic resonance imaging was typical of a Brenner tumor; fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) findings revealed mild FDG uptake and calcification in the solid component. These findings of PET/CT are often found in ovarian mucinous carcinomas. Our case suggests that magnetic resonance imaging is superior to FDG PET/CT for the differential diagnosis of ovarian Brenner tumors from other malignant tumors.

Prevalence of esophageal cancer during the pretreatment of hypopharyngeal cancer patients: routinely performed esophagogastroduodenoscopy and FDG-PET/CT findings.

BACKGROUND: The prevalence of esophageal cancer accompanied by hypopharyngeal cancer (HPC) is high and increasing rapidly in Asia. The purpose of this prospective study was to evaluate the prevalence of esophageal cancer during the pretreatment of HPC patients who were routinely examined using esophagogastroduodenoscopy (EGD) and 18F-fluorodeoxyglucose/computed tomography (FDG-PET/CT) and to discuss the utility of these examinations. MATERIAL AND METHODS: Between September 2005 and September 2010, 33 patients with newly diagnosed HPC (all with squamous cell carcinoma) underwent EGD (after a conventional endoscopy, iodine staining was performed) and FDG-PET/CT examinations. We evaluated the prevalence of esophageal cancer among HPC patients according to the EGD findings and determined the sensitivity of FDG-PET/CT for the detection of esophageal primary tumors for each clinical T classification. RESULTS: In 17 of the 33 patients (51.5%), 29 biopsy-proven esophageal squamous cell carcinomas were diagnosed using EGD. In eight of the 17 (47.1%) patients, two or more esophageal cancer lesions were diagnosed. Twenty-four of the 29 (82.8%) lesions were superficial esophageal cancers, and the remaining five (17.2%) lesions were advanced esophageal cancers. In six of the 29 (20.7%) esophageal cancer lesions that were detected using FDG-PET/CT, only one of the 29 (3.4%) lesions was evaluated as being equivocal; the remaining 22 (75.9%) lesions were not detected. The distribution of the clinical T classifications detected using FDG-PET/CT was as follows: T1a, 0/21 (0%); T1b, 1/3 (33%); and T3, 5/5 (100%). CONCLUSIONS: The prevalence of esophageal cancer during the pretreatment of HPC patients was 51.5%; this prevalence was higher than that in previous reports. We believe that the increasing proportion of superficial lesions (82.8%) detected using iodine staining and EGD may have led to the relatively high prevalence. FDG-PET/CT detected only 20.7% of the esophageal cancers, although FDG-PET/CT is capable of detecting unexpected primary malignant tumors other than esophageal cancer.

Utility of F-18 FDG PET/CT in screening for paraneoplastic neurological syndromes.

PURPOSE: The aim of this study was to assess the utility of positron emission tomography/computed tomography (PET/CT) for the investigation of patients with suspected paraneoplastic neurologic syndrome (PNS). MATERIALS AND METHODS: We reviewed the whole-body fluorodeoxyglucose (FDG) PET/CT studies (ordered by the neurology department) performed at our hospital between December 2005 and November 2010; 27 cases (16 men, 11 women; mean age, 65 years) who were suspected of having PNS were selected. RESULTS: Of the 27 patients, 6 (22%) had an abnormal FDG uptake. Of these 6 patients, 5 (19%) were histologically confirmed as having a malignancy. Of the 27 patients, 7 were tested for the presence of well-characterized paraneoplastic antibodies (anti-Hu, anti-Ri, anti-Yo); 1 had anti-Hu, but the patient did not have an abnormal FDG uptake or malignancy. CONCLUSIONS: PET/CT may be a useful screening tool for patients with clinically suspected PNS who do not exhibit well-characterized paraneoplastic antibodies. Therefore, we recommended that PET/CT should be performed for patients with clinically suspicious PNS regardless of the presence of well-characterized paraneoplastic antibodies.