Hidekatsu Shibata

Is diffusion-weighted magnetic resonance imaging superior to positron emission tomography with fludeoxyglucose F 18 in imaging non–small cell lung cancer?

OBJECTIVE This retrospective analysis examined whether diffusion-weighted magnetic resonance imaging might be as useful as positron emission tomography with fludeoxyglucose F 18 for (1) discriminating between non-small cell lung cancer and benign pulmonary nodules and (2) predicting aggressiveness of non-small cell lung cancer. METHODS Diffusion-weighted magnetic resonance imaging and positron emission tomography were performed before surgery in 110 patients with 124 pulmonary nodules smaller than 3 cm, including 96 non-small cell lung cancers and 28 benign nodules. Diffusion of water molecules in magnetic resonance imaging was measured by minimum value of apparent diffusion coefficient. The criterion standard was the result of histologic diagnosis or follow-up examination. Sensitivity and specificity for differentiating between cancers and benign nodules were compared between diffusion-weighted imaging and positron emission tomography. Apparent diffusion coefficient in diffusion-weighted imaging and fludeoxyglucose F 18 uptake in positron emission tomography were examined with respect to pathologic tumor stage; lymphatic, vascular and pleural involvements; and histologic differentiation. RESULTS There were no significant differences between diffusion-weighted magnetic resonance imaging and positron emission tomography in sensitivity or specificity for non-small cell lung cancer. Whereas positron emission tomography showed significant differences in fludeoxyglucose F 18 uptake between pathologic stages IA versus IB or more advanced stages; between tumors with and without lymphatic, vascular, or pleural involvement; and between well-differentiated and moderately or poorly differentiated adenocarcinomas (P <.01-0.001), no significant differences in apparent diffusion coefficient values in were observed. CONCLUSION Diffusion-weighted magnetic resonance imaging is equivalent to positron emission tomography in distinguishing non-small cell lung cancer from benign pulmonary nodules but is not as useful for predicting aggressiveness of non-small cell lung cancer.

Quantification of the impact of segmentectomy on pulmonary function by perfusion single-photon-emission computed tomography and multidetector computed tomography

OBJECTIVE The impact of segmentectomy for preservation of pulmonary function was quantified by using a co-registered perfusion single-photon-emission computed tomography and multidetector computed tomography (SPECT/CT). METHODS Pulmonary function tests and perfusion SPECT/CT were conducted before and after segmentectomy in 56 patients. Actual values of forced expiratory volume in 1 second (FEV(1)) after segmentectomy were compared with the FEV(1) after virtual lobectomy, which was calculated by SPECT/CT. The preoperative and postoperative FEV(1) of each lobe that had undergone segmentectomy was measured by SPECT/CT. RESULTS The mean percent of FEV(1) preserved after segmentectomy was significantly higher than the value after virtual lobectomy (88% +/- 9% vs 77% +/- 7%; P < .001). Whereas the mean value of the preoperative FEV(1) of each lobe that was undergoing segmentectomy was 0.51+/-0.21 L, segmentectomy could preserve 41% +/- 24% of it. The FEV(1) of each lobe after the resection of more than three segments (n = 4) was preserved in 17% +/- 12% of the preoperative values, which was significantly less than 49% +/- 23% and 35% +/- 22% after the resection of one (n = 29) and two (n = 23) segments (P = .02 and .08, respectively). The FEV(1) of the left upper lobe after the upper division segmentectomy (n = 8) was preserved in 21% +/- 11% of the preoperative values, which was significantly less than 35% +/- 12% after the lingular segmentectomy (n = 7) (P = .03). CONCLUSION Segmentectomy can preserve the pulmonary function more significantly than lobectomy, except for the resection of more than three segments or the left upper division segmentectomy.

18F-fluorodeoxyglucose and 11C-acetate positron emission tomography are useful modalities for diagnosing the histologic type of thymoma

The objective of this study was to clarify the usefulness of positron emission tomography (PET) using18F‐fluorodeoxyglucose (FDG) and carbon 11‐labeled acetate (AC) for predicting the histologic types and tumor invasiveness of thymoma in a multicenter study.

Prediction of pulmonary function after lung lobectomy by subsegments counting, computed tomography, single photon emission computed tomography and computed tomography: a comparative study

OBJECTIVE The aim of the present study was to determine the optimal method of predicting postoperative pulmonary function (PPF) after lung lobectomy. METHODS The forced expiratory volume in 1s (FEV(1)) was measured in 37 patients before and after lobectomy, and the following three methods of predicting the PPF were evaluated: (1) the number of functioning subsegments to be resected were counted (subsegments counting [SC]); (2) the volume of the functioning lung was calculated using CT images (quantitative CT); and (3) perfusion scintigraphy was performed using co-registered single photon emission computed tomography and CT imaging (SPECT/CT). The FEV(1) values predicted using these three methods were then compared with the measured postoperative FEV(1), and the correlations and differences were analyzed. RESULTS While a paired t-test showed the SPECT/CT method to have the smallest difference between the measured and the predicted FEV(1) values (0.05 l, p=0.33), followed by the quantitative CT method (0.07 l, p=0.07), and finally the SC method (0.15 l, p<0.001), the difference between the two values was not significantly different between the quantitative CT and SPECT/CT method (p=0.22). CONCLUSIONS While the SC method is inferior to both the quantitative CT and the SPECT/CT methods for predicting the PPF after lobectomy, the latter two methods are almost equally accurate.

Epidermal Growth Factor Receptor Mutations in Multicentric Lung Adenocarcinomas and Atypical Adenomatous Hyperplasias

Background: The mechanisms of generation and progression of multicentric lung adenocarcinoma (AD), bronchioloalveolar carcinoma (BAC), and atypical adenomatous hyperplasia (AAH) in the peripheral lung is not well known. In this study, we analyzed epidermal growth factor receptor (EGFR) mutations in the cases of multicentric AD, BAC, and AAH to reveal the role of EGFR mutation in their generations and progressions. Method: Ninety-seven AAH, BAC, or AD lesions less than 3 cm in size in 26 patients were surgically resected. Of these, EGFR mutations of the nodules with the highest and the second highest grade of histologic malignancy were examined in each patient by using the peptide nucleic acid-locked nucleic acid polymerase chain reaction (PNA-LNA PCR) clamp method. Results: EGFR mutations could be examined in 48 nodules in the 26 patients. The EGFR mutations were found more frequently in lesions with higher histologic malignancy, ie, 9 of 10 ADs (90%), 16 of 28 BACs (57%), and one of 10 AAHs (10%). In 22 patients who could be examined of EGFR mutations for the two lesions in each patient, only two patients (9%) had the same mutation patterns between the two lesions, whereas 15 patients (68%) had the different statuses and the remaining five (23%) had no mutations. Conclusion: Our data demonstrated that EGFR mutations seem to contribute to the acquisition of malignant potential in the AAH-AD sequence and occur independently in each lesion and in the cases of multicentric AD, BAC, and AAH.

Required area of lymph node sampling during segmentectomy for clinical stage IA non-small cell lung cancer

OBJECTIVE To investigate the required area of lymph node sampling during segmentectomy, especially for segmental nodes at the nonresected segments, we examined the distribution of sentinel nodes in patients with non-small cell lung cancer who underwent segmentectomy. METHODS Ninety-four patients with clinical T1 N0 M0 non-small cell lung cancer were treated by using segmentectomy and dissection of lymph nodes with sentinel node identification using (99m)Tc-phytate. Anatomic locations of the segments were classified as either anterior or posterior, and correlations of anatomic location with the distribution of sentinel nodes at the segmental nodes were then examined. RESULTS Of the 94 patients, segmental nodes at both the resected and nonresected segments could be dissected in 42 patients. Segmental sentinel nodes were found at the resected segments in 27 (64%) of these 42 patients, a frequency that was significantly higher than that (12/42 [29%]) seen at the nonresected segments (P = .001). Seven (47%) of the 15 patients with tumors in the anteriorly located segments had segmental sentinel nodes at the nonresected segments, a frequency that was significantly higher than that (4/24 [17%]) seen in patients with tumors in the posteriorly located segments (P = .04). CONCLUSION The lymphatic flow from the anteriorly located segment can frequently go directly to the segmental lymph nodes of the posteriorly located segment, probably because the lobar bronchi locate at the posterior side in the thorax. Therefore segmental lymph nodes should be dissected at both the resected and nonresected segments during segmentectomy, especially for tumors in the anteriorly located segment.

Long interspersed nucleotide element 1 hypomethylation is associated with poor prognosis of lung adenocarcinoma.

BACKGROUND Genome-wide DNA hypomethylation is known to play important roles in genomic instability and carcinogenesis. Methylation in long interspersed nucleotide element 1 (LINE-1) is a good indicator of the global DNA methylation level within a cell. The aim of this study was to evaluate prognostic significance of LINE-1 hypomethylation in lung adenocarcinoma. METHODS A consecutive series of 211 lung adenocarcinoma patients who underwent curative resections without any preoperative chemotherapy or radiotherapy at Kumamoto University Hospital between April 2010 and December 2012 were included. The LINE-1 methylation levels were quantified in tumor and noncancerous tissue by Pyrosequencing assay. RESULTS Higher histologic grade and positive findings for vascular invasion were significantly associated with lower methylation levels. The disease-free survival in the hypomethylation group was significantly shorter than that of the non-hypomethylation group. The prognostic difference was more obvious in advanced cases (stage II, III) than in stage I cases. CONCLUSIONS The LINE-1 methylation level is associated with histologic grade and vascular invasion of lung adenocarcinoma. Additionally, LINE-1 hypomethylation is a useful biomarker to predict early recurrence of lung adenocarcinoma.

Difference of Sentinel Lymph Node Identification Between Tin Colloid and Phytate in Patients With Non–Small Cell Lung Cancer

BACKGROUND The advantages and disadvantages of technetium Tc 99m tin colloid and technetium Tc 99m phytate as tracers for sentinel node (SN) identification in patients with clinical stage I non-small cell lung cancer were examined retrospectively. METHODS Sentinel node identification was conducted using tin colloid and phytate, respectively, in 73 and 74 patients with clinical stage I non-small cell lung cancer. We compared these two tracers in terms of identification rates, numbers of SNs, characteristics of patients whose SNs could not be identified, and the pathologic results of SNs. RESULTS The tin colloid tracer identified SNs in 54 of the 73 patients (74%), which was significantly lower than the 89% (66 of 74 patients) in the phytate group (p = 0.02). The number of SNs per patient was 1.7 +/- 0.8 in the tin colloid group, which was significantly less than the 2.4 +/- 1.5 in the phytate group (p = 0.002). Although patients in the tin colloid group whose SNs could not be identified had a significantly lower forced expiratory volume in 1 second to forced vital capacity ratio than those whose SNs could be identified (p = 0.04), the phytate group did not show such a difference. Eleven of 120 patients whose SNs could be identified had pathologic N1 or N2 disease, but neither group showed any false-negative results for SN identification. CONCLUSIONS Both tin colloid and phytate are reliable tracers for identifying SNs in non-small cell lung cancer. The advantage of phytate is that SNs can be detected more frequently than with tin colloid, even in patients with a low forced expiratory volume in 1 second to forced vital capacity ratio. However, tin colloid requires fewer nodes than phytate to identify SNs.

Evaluation of Semiquantitative Assessments of Fluorodeoxyglucose Uptake on Positron Emission Tomography Scans for the Diagnosis of Pulmonary Malignancies 1 to 3 cm in Size

BACKGROUND To determine the optimal method of evaluating fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) for the diagnosis of pulmonary malignancies, the sensitivity and specificity of visual assessment and the several semiquantitative analyses were compared. METHODS Positron emission tomography data were analyzed for 130 pulmonary nodules from 1 to 3 cm in size (101 malignant and 29 benign nodules). The FDG uptake was measured by maximum standard uptake value (SUVmax), the contrast ratio (CR) of the SUV to the cerebellum (CR brain), and the CR of the SUV to the contralateral lung (CR lung). The CR lung was calculated from the SUV of the tumor (T) and that of the contralateral normal lung (N) and then was measured by two formulas, namely, T-N/T+N and T/N. RESULTS The sensitivities of both CR lung T-N/T+N and CR lung T/N were significantly higher than those of visual assessment, SUVmax, and CR brain (p = 0.01 to p < 0.001). No significant difference in sensitivity was observed between the CR lung T-N/T+N and CR lung T/N. Both CR lung T-N/T+N and CR lung T+N successfully imaged well-differentiated lung adenocarcinoma more frequently than the visual assessment, SUVmax, and CR brain (p = 0.002 to p < 0.001), whereas there were no significant differences of sensitivity among those five methods for the diagnosis of other histologic types of pulmonary malignancies. CONCLUSIONS The FDG uptake evaluated by the CR lung is superior to that evaluated using the visual assessment, SUVmax, and CR brain for the diagnosis of pulmonary malignancies, especially for well-differentiated lung adenocarcinoma. The simplified formula of CR lung with T/N can be used in place of that with T-N/T+N.

11C-Acetate can be Used in Place of 18F-Fluorodeoxyglucose for Positron Emission Tomography Imaging of Non-small Cell Lung Cancer with Higher Sensitivity for Well-Differentiated Adenocarcinoma

Objectives: Although positron emission tomography (PET) using 18F-fluorodeoxy-glucose (FDG) frequently gives false-negative results for slow-growing tumors, 11C-acetate (AC)-PET has been reported to be able to detect them. To determine the usefulness of AC-PET for imaging non-small cell lung cancers (NSCLCs), the sensitivity and specificity were compared between the AC-PET and FDG-PET with a multicenter study. Materials and Methods: A total of 284 pulmonary lesions (227 NSCLCs and 57 benign lesions) were examined using both AC-PET and FDG-PET before surgery at seven Japanese institutes. The AC- or FDG-uptake in each lesion were quantitatively measured using the contrast ratio of the standard uptake value between the lesions and the contralateral lung. Results: The sensitivity of AC-PET for diagnosing NSCLC was 0.71, which was significantly higher than the value of 0.57 obtained by FDG-PET (p < 0.001). No significant difference in the specificity was seen between AC- and FDG-PET. For the 146 well-differentiated adenocarcinomas, the sensitivity of AC-PET was 0.62, which was significantly higher than the value of 0.37 obtained by FDG-PET (p < 0.001). Of the 51 moderately- or poorly-differentiated adenocarcinomas and 30 nonadenocarcinomas, there was no significant difference of sensitivity between AC- and FDG-PET. Conclusions: AC-PET could be used in place of FDG-PET for imaging NSCLC, with higher sensitivity for well-differentiated adenocarcinoma compared with FDG-PET.