Impact of retention index on the neoadjuvant chemotherapy effect and the prognosis in oesophageal cancer.

OBJECTIVE: The relationship between retention index calculated from dual-time point 18F-fluorodeoxyglucose positron emission tomography-computed tomography and oesophageal cancer prognosis remains unknown. This study aimed to determine usefulness of retention index as a predictor of long-term prognosis of oesophageal cancer and neoadjuvant chemotherapy efficacy. METHODS: A total of 151 patients with oesophageal cancer who underwent esophagectomy were evaluated retrospectively in this study. We acquired positron emission tomography scans 60 and 120 min (SUVmax1 and SUVmax2, respectively) after the intravenous administration of 3.7 Mbq/kg 18F-fluorodeoxyglucose. The patients were divided into two groups: high-retention index (retention index ≥29%, 107 patients) and low-retention index (retention index <29%, 44 patients). Retention index was calculated as follows: retention index (%) = [(SUVmax2 - SUVmax1)/SUVmax1] × 100. RESULTS: The overall survival and relapse-free survival rates in the high-retention index group were significantly lower than those in the low-retention index group (P < 0.001). Our multivariate analysis identified that the high-retention index group contained independent risk factors for overall survival (hazard ratio: 2.44, P = 0.009) and relapse-free survival (hazard ratio: 2.61, P = 0.002). The high-retention index group exhibited a lower partial response rate to neoadjuvant chemotherapy evaluated by computed tomography (P < 0.001) and a lower pathological therapeutic effect in the resected specimen (P = 0.019) than the low-retention index group. CONCLUSIONS: The retention index was associated with neoadjuvant chemotherapy responses and long-term prognosis for oesophageal cancer.

Impact of sleep-related hypoventilation in patients with pleuroparenchymal fibroelastosis.

BACKGROUND: Pleuroparenchymal fibroelastosis (PPFE) is a rare fibrosing lung disease with a predilection for the upper lobe and its progression causes hypoventilation, resulting in hypercapnia. Even though the association between sleep-related hypoventilation (SRH) and chronic obstructive pulmonary disease was well documented, its impact in patients with PPFE was not evaluated. The aim of this study is to clarify the impact of SRH on prognosis in PPFE. METHODS: A retrospective review of the medical records of 52 patients with PPFE who underwent transcutaneous carbon dioxide monitoring during sleep was done. Patients were stratified into SRH (n = 28) and non-SRH (n = 24) groups based on American Academy of Sleep Medicine criteria. The impact of SRH on the prognosis of PPFE, as well as the clinical factors and comorbidities of PPFE associated with SRH, were evaluated. RESULTS: Forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), total lung capacity (TLC), and carbon monoxide diffusing capacity (DLco) in the SRH group were significantly lower than the non-SRH group (P < .01). Chronic pulmonary aspergillosis (CPA) was found at a higher rate in the SRH group (P = .02). The median survival time for SRH patients was 330 days, whereas roughly 80% of non-SRH patients were alive during the 3-year observation period (P < .01). Body mass index was a significant prognostic factor in PPFE patients with SRH (HR .78; 95% CI; .64-.94; P < .01). Home oxygen therapy (HOT) during the day and noninvasive positive pressure ventilation (NPPV) at night while sleeping tended to improve prognosis in the SRH group, as indicated by HR of .25 (P = .07). CONCLUSIONS: SRH may be a poor prognostic factor for PPFE. Additionally, SRH may modify susceptibility to Aspergillosis in patients with PPFE. HOT plus NPPV may improve the disease outcomes in patients with SRH.

Preoperative CA19­9 level and dual time point FDG­PET/CT as strong biological indicators of borderline resectability in pancreatic cancer: A retrospective study.

Tumor resectability, which is increasingly determined based on preoperative chemotherapy, is critical in determining the best treatment for pancreatic cancers. The present study evaluated the usefulness of serum carbohydrate antigen 19-9 (CA19-9) and the preoperative 8F-fluorodeoxyglucose positron emission tomography/computed tomography standardized uptake value (SUV) percentage change (SUVmax%=[(SUVmax2-SUVmax1)/SUVmax1] ×100, where SUVmax1 and SUVmax2 represent the initial and delayed phases, respectively) as biological factors indicative of tumor resectability. The present study included patients with resectable pancreatic cancer who underwent complete surgical resection, for whom both CA19-9 and SUVmax% were documented using cut-off values of 500 U/ml and 24.25%, respectively. Patients were classified as follows: i) High CA19-9 and SUVmax%: both CA19-9 and SUVmax% were elevated; ii) high CA19-9 or SUVmax%: either CA19-9 or SUVmax% were elevated; or iii) low CA19-9 and SUVmax%: neither value met the cut-off. Relapse-free survival (RFS) and overall survival (OS) were calculated, for which univariate and multivariate analyses were performed. Of the 86 patients included, 39 were classified as high CA19-9 or SUVmax% and 12 as high CA19-9 and SUVmax%, with the former group having a significantly worse RFS (vs. low CA19-9 and SUVmax%; P<0.001; vs. high CA19-9 or SUVmax%; P=0.011) and OS (vs. low CA19-9 and SUVmax%, P=0.002; vs. high CA19-9 or SUVmax%, P<0.001). Therefore, high CA19-9 and SUVmax% was an independent predictor of worse RFS (P<0.001) and OS (P=0.003). In conclusion, CA19-9 and SUVmax% can be utilized as biological indicators of resectability.

18F-fluorodeoxyglucose positron emission tomography optimizes neoadjuvant chemotherapy for primary breast cancer to achieve pathological complete response.

BACKGROUND: To assess the usefulness of positron emission tomography combined with computed tomography using (18)F-fluorodeoxyglucose (FDG PET/CT) for optimizing chemotherapy during neoadjuvant chemotherapy for primary breast cancer. METHODS: One hundred and eight patients (110 tumors) with breast cancer (≥2 cm, stages II and III) received neoadjuvant chemotherapy consisting of an anthracycline-based regimen and taxane. The maximal value of the baseline standardized uptake value (SUV) and the change in SUV after four cycles of an anthracycline-based regimen relative to baseline SUV were assessed for predicting pathological complete response (pCR) after sequential taxane. RESULTS: Tumors with pCR had significantly higher baseline SUV (9.3 ± 3.7 SD) compared to those with non-pCR (7.2 ± 3.8 SD) (p = 0.02), but there was a considerable overlap between two groups. On PET scan after four cycles of chemotherapy, thirty-three patients (33.7%) with a 72.1% or greater reduction in SUV were considered as responders and the performance in predicting pCR had a sensitivity of 88.9% and specificity of 78.7%. CONCLUSION: The baseline SUV could not be a useful indicator for predicting pCR due to the wide range in sensitivity. On the other hand, a relative change in SUV after completion of an anthracycline-based regimen could be useful for predicting pCR.

Atorvastatin Reduces Circulating S100A12 Levels in Patients with Carotid Atherosclerotic Plaques - A Link with Plaque Inflammation.

AIMS: Inflammation is involved in various processes of atherosclerosis development. Serum C-reactive protein (CRP) levels, a predictor for cardiovascular risk, are reportedly reduced by statins. However, several studies have demonstrated that CRP is a bystander during atherogenesis. While S100A12 has been focused on as an inflammatory molecule, it remains unclear whether statins affect circulating S100A12 levels. Here, we investigated whether atorvastatin treatment affected S100A12 and which biomarkers were correlated with changes in arterial inflammation. METHODS: We performed a prospective, randomized open-labeled trial on whether atorvastatin affected arterial (carotid and thoracic aorta) inflammation using 18fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) and inflammatory markers. Thirty-one statin-naïve patients with carotid atherosclerotic plaques were randomized to either a group receiving dietary management (n=15) or one receiving atorvastatin (10mg/day, n=16) for 12weeks. 18F-FDG-PET/CT and flow-mediated vasodilation (FMD) were performed, the latter to evaluate endothelial function. RESULTS: Atorvastatin, but not the diet-only treatment, significantly reduced LDL-cholesterol (LDL-C, -43%), serum CRP (-37%) and S100A12 levels (-28%) and improved FMD (+38%). 18F-FDG-PET/CT demonstrated that atorvastatin, but not the diet-only treatment, significantly reduced accumulation of 18F-FDG in the carotid artery and thoracic aorta. A multivariate analysis revealed that reduction in CRP, S100A12, LDL-C, oxidized-LDL, and increase in FMD were significantly associated with reduced arterial inflammation in the thoracic aorta, but not in the carotid artery. CONCLUSIONS: Atorvastatin treatment reduced S100A12/CRP levels, and the changes in these circulating markers mirrored the improvement in arterial inflammation. Our observations suggest that S100A12 may be an emerging therapeutic target for atherosclerosis.

18F-fluorodeoxyglucose-positron emission tomography/computed tomography for the diagnosis of polymyalgia-like illnesses: a retrospective study.

BACKGROUND: Various inflammatory conditions may present with musculoskeletal symptoms similar to those of polymyalgia rheumatica (PMR). We investigated findings on 18F-fluorodexoxyglucose (FDG)-positron emission tomography/computed tomography (PET/CT) images that may differentiate PMR from polymyalgia-like illnesses. METHODS: We analyzed data from 25 patients with new-onset polymyalgia-like illnesses who fulfilled Bird's diagnostic criteria for PMR and had undergone FDG-PET/CT scan. To assess the uptake by major joints and synovial bursae, particularly at PMR-specific sites (shoulder, sternoclavicular, and hip joints, interspinous bursae, ischial tuberosities, and greater trochanters), we used visual scoring system to score FDG uptake: 0, no uptake (same as bone); 1, slight uptake; 2, moderate uptake (same as the liver); 3, greater uptake than the liver; and 4, uptake as strong as in the cerebellum. RESULTS: The final diagnoses were PMR in 17 patients and non-PMR in eight patients (three malignancies, two infections, one cholesterol crystal embolism, one ANCA-associated vasculitis, and one undefined diagnosis). Although the serum MMP-3 levels were significantly higher in patients with PMR, C-reactive protein and erythrocyte sedimentation rate mean values did not differ between the two groups. In PMR-specific sites, FDG accumulations were observed in all cases of PMR, with a high PET-positive score of 2.00 (range, 0-3), but it was low in non-PMR cases, with a PET-positive score of 1.00 (range, 0-3). CONCLUSIONS: The FDG accumulation patterns in polymyalgia-like illness differ from those in PMR, despite the similar clinical presentations of both conditions. An FDG-PET/CT scan is useful for differentiating PMR from other polymyalgia-like illnesses.

Carbon-11-methionine PET imaging of choroidal melanoma and the time course after carbon ion beam radiotherapy.

UNLABELLED: The aim of this study was to assess the feasibility of MET-PET as an evaluation method of the therapeutic effect of carbon ion beam radiotherapy. PATIENTS AND METHODS: Twenty-four choroidal melanoma patients who were treated with a carbon ion beam underwent at least three MET-PET scans before and after therapy. The uptake was visually and semiquantitatively evaluated on the basis of the tumor-to-brain ratio (TBR). RESULTS: The accumulation was significantly decreased at 6 months or more after therapy and disappeared in 50% of the patients at 12 months after therapy. The baseline TBR, 1, 6, 12 and 24 months after therapy averaged 1.88+/-0.65, 1.73+/-0.52, 1.08+/-0.42, 0.67+/-0.27 and 0.65+/-0.30, respectively. TBR was significantly decreased at 6 months or more after therapy. CONCLUSION: MET-PET may be an alternative method for evaluating the effect of radiotherapy.

Malignant pleural mesothelioma initially diagnosed on cervical lymph node biopsy.

Reported herein is a case of malignant pleural mesothelioma, initially diagnosed on cervical lymph node biopsy. A 58-year-old man, without obvious evidence of asbestos exposure, exhibited repeated pleural effusion (cause unclear), which was resolved by diuretics. A neck mass was apparent and was identified pathologically as a lymph node metastasis of malignant mesothelioma. F-18 fluorodeoxyglucose positron emission tomography/CT established the diagnosis of malignant pleural mesothelioma. Two conclusions emerge from this report: (i) cervical lymph node metastasis of pleural mesothelioma, although rare, should be included in differential diagnosis; and (ii) positron emission tomography/CT is useful for establishing a diagnosis of mesothelioma.

11C-methionine-PET for evaluation of carbon ion radiotherapy in patients with pelvic recurrence of rectal cancer.

PURPOSE: Progress of the novel carbon ion radiotherapy (CIRT) in the treatment of cancers has created the need for a method to accurately evaluate the response. We investigated whether L-[11C]methyl-methionine (11C-methionine) uptake at pre- and post-CIRT could be an early response predictor in patients with pelvic recurrence of rectal cancer. PROCEDURES: 11C-Methionine-positron emission tomography (PET) was performed prospectively in 53 patients with pelvic recurrence of rectal cancer before CIRT, and 48 patients were performed 11C-methionine PET at 1 month after CIRT. 11C-Methionine tumor uptake was measured by the tumor to muscle ratio (T/M ratio). The T/M ratios were evaluated in relation to clinical outcomes such as local re-recurrence, distant metastasis, and survival. The response to CIRT was also judged by computed tomography (CT) and magnetic resonance imaging (MRI). 11C-Methionine PET judgment was compared with CT/MRI judgment regarding the relevance to clinical outcome. RESULTS: Baseline T/M ratio was 5.27+/-1.90 (mean+/-SD) in patients without developing local re-recurrence and 7.66+/-3.17 in patients with local re-recurrence (p=0.023, Mann-Whitney U test). Post-CIRT T/M ratios were 3.10+/-1.28 in patients without local re-recurrence and 6.15+/-2.98 in patients with local re-recurrence (p=0.006, Mann-Whitney U test). By Kaplan-Meier analysis with log-rank test, patients with a baseline T/M ratio of

Utility of 18F-fluoro-deoxyglucose emission tomography/computed tomography fusion imaging (18F-FDG PET/CT) in combination with ultrasonography for axillary staging in primary breast cancer.

BACKGROUND: Accurate evaluation of axillary lymph node (ALN) involvement is mandatory before treatment of primary breast cancer. The aim of this study is to compare preoperative diagnostic accuracy between positron emission tomography/computed tomography with 18F-fluorodeoxyglucose (18F-FDG PET/CT) and axillary ultrasonography (AUS) for detecting ALN metastasis in patients having operable breast cancer, and to assess the clinical management of axillary 18F-FDG PET/CT for therapeutic indication of sentinel node biopsy (SNB) and preoperative systemic chemotherapy (PSC). METHODS: One hundred eighty-three patients with primary operable breast cancer were recruited. All patients underwent 18F-FDG PET/CT and AUS followed by SNB and/or ALN dissection (ALND). Using 18F-FDG PET/CT, we studied both a visual assessment of 18F-FDG uptake and standardized uptake value (SUV) for axillary staging. RESULTS: In a visual assessment of 18F-FDG PET/CT, the diagnostic accuracy of ALN metastasis was 83% with 58% in sensitivity and 95% in specificity, and when cut-off point of SUV was set at 1.8, sensitivity, specificity, and accuracy were 36, 100, and 79%, respectively. On the other hand, the diagnostic accuracy of AUS was 85% with 54% in sensitivity and 99% in specificity. By the combination of 18F-FDG PET/CT and AUS to the axilla, the sensitivity, specificity, and accuracy were 64, 94, and 85%, respectively. If either 18F-FDG PET uptake or AUS was positive in allixa, the probability of axillary metastasis was high; 50% (6 of 12) in 18F-FDG PET uptake only, 80% (4 of 5) in AUS positive only, and 100% (28 of 28) in dual positive. By the combination of AUS and 18F-FDG PET/CT, candidates of SNB were more appropriately selected. The axillary 18F-FDG uptake was correlated with the maximum size and nuclear grade of metastatic foci (p = 0.006 and p = 0.03). CONCLUSION: The diagnostic accuracy of 18F-FDG PET/CT was shown to be nearly equal to ultrasound, and considering their limited sensitivities, the high radiation exposure by 18F-FDG PET/CT and also costs of the examination, it is likely that AUS will be more cost-effective in detecting massive axillary tumor burden. However, when we cannot judge the axillary staging using AUS alone, metabolic approach of 18F-FDG PET/CT for axillary staging would enable us a much more confident diagnosis.

Expression of centromere protein F (CENP-F) associated with higher FDG uptake on PET/CT, detected by cDNA microarray, predicts high-risk patients with primary breast cancer.

BACKGROUND: Higher standardized uptake value (SUV) detected by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) correlates with proliferation of primary breast cancer. The purpose of this study is to identify specific molecules upregulated in primary breast cancers with a high SUV and to examine their clinical significance. METHODS: We compared mRNA expression profiles between 14 tumors with low SUVs and 24 tumors with high SUVs by cDNA microarray. We identified centromere protein F (CENP-F) and CDC6 were upregulated in tumors with high SUVs. RT-PCR and immunohistochemical analyses were performed to validate these data. Clinical implication of CENP-F and CDC6 was examined for 253 archival breast cancers by the tissue microarray. RESULTS: The relative ratios of CENP-F and CDC6 expression levels to beta-actin were confirmed to be significantly higher in high SUV tumors than in low SUV tumors (p = 0.027 and 0.025, respectively) by RT-PCR. In immunohistochemical analysis of 47 node-negative tumors, the CENP-F expression was significantly higher in the high SUV tumors (74%) than the low SUV tumors (45%) (p = 0.04), but membranous and cytoplasmic CDC6 expressions did not significantly differ between both groups (p = 0.9 each). By the tissue microarray, CENP-F (HR = 2.94) as well as tumor size (HR = 4.49), nodal positivity (HR = 4.1), and Ki67 (HR = 2.05) showed independent impact on the patients' prognosis. CONCLUSION: High CENP-F expression, correlated with high SUV, was the prognostic indicators of primary breast cancer. Tumoral SUV levels may serve as a pretherapeutic indicator of aggressiveness of breast cancer.

Clinicopathological and prognostic relevance of uptake level using 18F-fluorodeoxyglucose positron emission tomography/computed tomography fusion imaging (18F-FDG PET/CT) in primary breast cancer.

OBJECTIVE: Using integrated 18F-fluorodeoxyglucose positron emission tomography/computed tomography fusion imaging (18F-FDG PET/CT), the clinical significance of 18F-FDG uptake was evaluated in patients with primary breast cancer. METHODS: Clinicopathological correlation with the level of maximum standardized uptake values (SUV) 60 min obtained from preoperative 18F-FDG PET/CT were examined in 152 patients with primary breast cancer. The prognostic impact of the level of SUV was explored using simulated prognosis derived from computed program Adjuvant! in 136 (89%) patients with invasive ductal carcinoma (IDC). RESULTS: High SUV level was significantly correlated with tumor invasive size (< or = 2 cm) (P < 0.0001), higher score of nuclear grade (P < 0.0001), nuclear atypia (P < 0.0001) and mitosis counts (P < 0.0001), negative hormone receptor status (P = 0.001), high score of c-erbB-2 expression (P = 0.006), lymph node metastasis (P = 0.002), and IDC in comparison with invasive lobular carcinoma (P = 0.004). Multivariate analyses showed tumor invasive size, nuclear grade and estrogen receptor negativity were significantly correlated with SUV in primary breast cancer (P < 0.0001,< 0.0001, and < 0.012, respectively), and nuclear grade was significantly correlated with SUV in tumors of invasive size 2 cm or less (P < 0.0001). Tumors with high SUV (cutoff value 4.0) showed higher relapse and mortality rate compared to those with low SUV (P < 0.0001). CONCLUSIONS: High uptake of 18F-FDG would be predictive of poor prognosis in patients with primary breast cancer, and aggressive features of cancer cells in patients with early breast cancer. 18F-FDG PET/CT could be a useful tool to pre-therapeutically predict biological characteristics and baseline risk of breast cancer.

[(11)C]methionine positron emission tomography and survival in patients with bone and soft tissue sarcomas treated by carbon ion radiotherapy.

PURPOSE: The development of the novel carbon ion radiotherapy (CIRT) in the treatment of refractory cancers has resulted in the need for a way to accurately evaluate patient prognosis. We evaluated whether L-[methyl-(11)C]-methionine (MET) uptake and its change after CIRT were the early survival predictors in patients with unresectable bone and soft tissue sarcomas. EXPERIMENTAL DESIGN: MET positron emission tomography was prospectively performed in 62 patients with unresectable bone and soft tissue sarcomas before and within 1 month after CIRT. Tumor MET uptake was measured with the semiquantitative tumor:nontumor ratio (T/N ratio). The MET uptake in the tumor and relevant clinical parameters were entered into univariate and multivariate survival analysis. RESULTS: The overall median survival time was 20 months. Patients with a baseline T/N ratio of 6 (2-year survival rate: 69.4% versus 32.3%; P = 0.01). Patients with a post-CIRT ratio of 4.4 (2-year survival rate: 63.7% versus 41.3%; P = 0.01). A significant higher survival rate was observed in patients with post-therapeutic MET uptake change of >30% than patients in lower change group (2-year survival rate: 74.6% versus 41.6%; P = 0.049). The multivariate analysis showed that both baseline and post-CIRT T/N ratio were statistically significant independent predictors of patient survival. Tumors with larger T/N ratio had a significantly poorer prognosis. CONCLUSIONS: MET uptake as measured by either baseline or post-CIRT T/N ratio was an independent predictor of survival in patients with bone and soft tissue sarcomas treated by carbon ion radiotherapy, whereas post-therapeutic MET uptake change might have potential value for the same purpose.

[Diagnosis of esophageal cancer using positron emission tomography].

Fluorodeoxyglucose positron emission tomography (FDG-PET) is more accurate than computed tomography (CT) for evaluating lymph node metastases and for N staging, but less accurate than combined CT and endoscopic ultrasonography (EUS). Lymph nodes located adjacent to the primary lesion tend to be false negatives. We consider that combined FDG-PET and EUS is the most accurate for the detection of lymph node metastasis in esophageal cancer. FDG-PET is also more accurate than CT for detecting distant metastases and improves the detection of stage IV disease compared with the conventional staging modalities. For the diagnosis of recurrence except for perianastomotic recurrence, FDG-PET provides additional information and is more sensitive than conventional work-ups. FDGPET is a valuable tool for the noninvasive assessment of tumor response after neoadjuvant therapy. 11C-methionine (MET) is another tracer for PET that can be used to assess the metabolism of amino acids, since MET accumulates in esophageal malignant tumors. Choline-PET is more accurate than FDG-PET for the detection of mediastinal lymph node metastases.

Prognostic factors for brain metastases from non-small cell lung cancer with EGFR mutation: influence of stable extracranial disease and erlotinib therapy.

The aim of this study was to explore prognostic factors for non-small cell lung cancer (NSCLC) patients with brain metastases (BM) on the basis of EGFR mutation status. Among 779 consecutive NSCLC patients who underwent EGFR mutation screening, all 197 patients with BM were divided according to the EGFR mutation status. The prognostic factors, including patient characteristics at the time of BM diagnosis, treatment history, and radiologic features, were analyzed. Of 197 patients with BM, 108 had wild-type EGFR and 89 had EGFR mutation. The patients with EGFR mutation presented longer overall survival after BM diagnosis (OS) than those with wild-type EGFR, regardless of whether BM was synchronous or metachronous. For the patients with EGFR mutation, favorable prognostic factors in multivariate analysis were age<65 (p=0.037), good performance status (PS) (p<0.0001), cranial radiotherapy (p=0.020), previous chemotherapy≤1 regimen (p=0.009), stable extracranial disease at BM diagnosis (p=0.022), and erlotinib therapy after BM diagnosis (p=0.0015). On the other hand, favorable prognostic factors for the patients with wild-type EGFR were only good PS (p=0.0037) and cranial radiotherapy (p=0.0005). Among patients treated with erlotinib after BM diagnosis, the patients with exon 19 deletion showed longer OS than those with exon 21 point mutation (p=0.019). The prognostic factors for NSCLC patients with BM were different according to the EGFR mutation status. Particularly in NSCLC patients with EGFR mutation and stable extracranial disease, regular cranial evaluation for detecting asymptomatic BM would lead to good prognosis. In addition, erlotinib therapy would be preferable in NSCLC patients with BM and EGFR mutation, especially those with exon 19 deletion.

A new in vivo model to analyze hepatic metastasis of the human colon cancer cell line HCT116 in NOD/Shi-scid/IL-2Rγ(null) (NOG) mice by (18)F-FDG PET/CT.

Clinically, (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG-PET/CT) is useful in the evaluation of various types of human cancers. While PET analysis has been established to evaluate subcutaneous lesions of human cancers in mice, its applications for internal lesions are still being developed. We are currently evaluating new PET approaches for the effective evaluation of in vivo metastatic lesions in the internal organs of small experimental animals. In this study, we analyzed in vivo hepatic metastases of human colonic cancer in immunodeficient mice (NOD/Shi-scid/IL-2Rγ(null), NOG) using PET imaging. This new PET approach has been proposed for the evaluation of in vivo metastatic lesions in internal organs. The human colon cancer line HCT116 (1.0x10(5) and 1.0x10(6) cells/mouse) was transplanted by intrasplenic injection. (18)F-FDG-PET/CT scans were performed 2 weeks after transplantation. After PET/CT scans, histopathological examinations were performed. PET/CT analysis disclosed multiple metastatic foci and increased standardized uptake values (SUV) of FDG in the livers of NOG mice (control, SUVmean 0.450±0.033, SUVmax 0.635±0.017; 1.0x10(5) cells, 0.853±0.087, 1.254±0.237; 1.0x10(6) cells, 1.211±0.108, 1.701±0.158). There were significant differences in FDG uptakes between the three groups (ANOVA, P=0.017 in SUVmean; P=0.044 in SUVmax, n=2). We clearly and quantitatively detected images of hepatic metastasis in the livers of NOG mice by (18)F-FDG-PET/CT in vivo. PET/CT analysis of internal organ lesions of human cancerous xenografts is a new reliable experimental system to simulate metastases. This model system is useful for analyzing metastatic mechanisms and for developing new novel drugs targeting hepatic metastases of cancer.

Prevalence of underlying lung disease in smokers with epidermal growth factor receptor-mutant lung cancer.

The prevalence of underlying lung diseases, such as emphysema and interstitial lung disease in smokers with epidermal growth factor receptor (EGFR)-mutant lung cancer remains unclear. This study aimed to clarify the correlation between the EGFR mutation status and the prevalence of underlying lung disease in smokers with lung cancer. A total of 88 consecutive smokers with non-small cell or non-squamous cell lung cancer who underwent surgical resection at our hospital from January 2007 through December 2010 were included in this study. The patients were divided into two groups on the basis of the EGFR mutation status: the mutation-positive group (n=19) and the wild-type group (n=69). The results of radiographic assessment via computed tomography (CT) and pulmonary function analysis were compared between the two groups. In the radiological evaluation, CT images at three levels were evaluated by two reviewers. Radiographic assessment revealed that the mutation-positive group tended to have milder emphysematous changes and a lower prevalence of interstitial changes compared with the wild-type group (P=0.13, 0.06). When the analysis was limited to the ipsilateral lung at the nearest CT level to the tumor, emphysematous changes were found to be less common in the mutation-positive group (P=0.02). The prevalence of the emphysematous and/or interstitial changes in the ipsilateral lung at the nearest CT level to the tumor was lower in the mutation-positive group compared to the wild-type group (P=0.005). In the pulmonary function test, the results were comparable between the two groups. In conclusion, according to our results, EGFR-mutant lung cancer was commonly observed in the areas where emphysematous and interstitial changes were absent. EGFR-mutant lung cancer may develop in radiographically normal areas of the lungs, even in smokers. It would be of importance to evaluate the EGFR mutation status in patients with no emphysematous or interstitial changes in the ipsilateral lung near the tumor, regardless of their smoking history. These results should be confirmed in a future prospective study.

A case of early stage lung cancer detected by repeated cancer screening with positron emission tomography.

There has been an increase in the detection rate of small early lung cancer due to recent improvements in imaging technology. However, conventional imaging modalities such as computed tomography (CT) alone are not capable of differentiating small pulmonary nodules. New modalities such as F-18 2'-deoxy-2fluoro-D-glucose (FDG) positron emission tomography combined with CT (PET/CT) have contributed to the evaluation of lung cancer staging, although the differential diagnosis of pulmonary nodules showing ground-glass opacity (GGO) with PET/CT is controversial. In Japan, cancer screening with whole body FDG-PET has been available for asymptomatic individuals, and it has been reported that a wide variety of cancer types are detectable by FDG-PET at potentially curable stages. We present the case of a 62-year-old male with early lung cancer, which was revealed by repeated health screening. A PET/CT scan revealed definite intense FDG uptake (SUVmax 1.2) in the pulmonary nodules of the right upper lobe, while no definite FDG uptake was observed in the lesion in the previous annual screening. Right upper lobectomy was performed, and the pathological diagnosis was well-differentiated adenocarcinoma. Five-year survival has been noted since the thoracotomy, and the patient is doing well without recurrence. This is a significant case of early lung cancer with GGO lesions, which revealed intense FDG uptake during an annual repeated health screening with FDG-PET/CT.

Clinical implications of 18F-fluorodeoxyglucose positron emission tomography/computed tomography at delayed phase for diagnosis and prognosis of malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) has a poor prognosis, and conventional imaging modalities do not reflect the prognosis of MPM. In this study, the clinical significance of 18F-fluorodeoxyglucose positron emission tomography/computed tomography fusion imaging (18F-FDG PET/CT) was evaluated for the differential diagnosis, staging and prognosis in MPM patients. Ninety patients who underwent 18F-FDG PET/CT scanning due to a clinical diagnosis or suspicion of MPM prior to therapy were reviewed. Of 90 patients, 31 were pathologically diagnosed as MPM. Maximum standardized uptake values (SUVmax) were semi-quantitatively obtained from PET/CT 60 min (early phase) and 120 min (delayed phase) after injection of 18F-FDG, and the clinicopathological correlations with the level of SUVmax obtained from PET/CT were examined. The survival curves of MPM patients were plotted according to the methods of Kaplan-Meier. The prognostic implications of the level of SUVmax were estimated by t-test. PET/CT scan showed intense abnormal FDG uptake (SUVmax>2.0) in the pleural lesions of all 31 MPM patients at delayed phase, while it showed abnormal FDG uptake in 30 (97%) patients at early phase. In all 31 MPM patients, the values of SUVmax at delayed phase were higher than those at the early phase. PET/CT also indicated metastasis in the lymph node in 7 patients (23%) and in the systemic lesions in 8 patients (26%) with MPM. Twenty-three MPM patients with high SUVmax, whose prognosis was apparent, showed significantly poorer prognosis in both early and delayed phase (respectively, p=0.03 and p=0.01, t-test). The results showed that 18F-FDG PET/CT at delayed phase is very useful for the diagnosis of pleural diseases, and SUVmax on PET/CT in the delayed phase is a more reliable prognostic factor than that in the early phase. High uptake of 18F-FDG PET/CT may be a predictive factor of prognosis in MPM patients.