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Supplementary Figure Legend from Autophagy Is Activated in Colorectal Cancer Cells and Contributes to the Tolerance to Nutrient Deprivation

Supplementary Figure 1 from Autophagy Is Activated in Colorectal Cancer Cells and Contributes to the Tolerance to Nutrient Deprivation

Several types of cancer cells, including colorectal cancer–derived cell lines, show austerity, the resistance to nutrient starvation, but exactly how cancer cells obtain energy sources under conditions in which their external nutrient supply is extremely limited remains to be clarified. Because autophagy is a catabolic process by which cells supply amino acids from self-digested organelles, cancer cells are likely to use autophagy to obtain amino acids as alternative energy sources. Amino acid deprivation-induced autophagy was assessed in DLD-1 and other colorectal cancer–derived cell lines. The autophagosome-incorporated LC3-II protein level increased after treatment with a combination of autolysosome inhibitors, which interferes with the consumption of autophagosomes. Autophagosome formation was also morphologically confirmed using ectopically expressed green fluorescent protein-LC3 fusion proteins in DLD-1 and SW480 cells. These data suggest that autophagosomes were actively produced and promptly consumed in colorectal cancer cells under nutrient starvation. Autolysosome inhibitors and 3-methyl adenine, which suppresses autophagosome formation, remarkably enhanced apoptosis under amino acid–deprived and glucose-deprived condition. Similar results were obtained in the cells with decreased ATG7 level by the RNA interference. These data suggest that autophagy is pivotal for the survival of colorectal cancer cells that have acquired austerity. Furthermore, autophagosome formation was seen only in the tumor cells but not in the adjacent noncancerous epithelial cells of colorectal cancer specimens. Taken together, autophagy is activated in colorectal cancers in vitro and in vivo, and autophagy may contribute to the survival of the cancer cells in their microenvironment. [Cancer Res 2007;67(20):9677–84]

A 66-year-old man was diagnosed with inoperable advanced gastric cancer with liver and peritoneal metastases. The patient underwent SOX therapy as primary chemotherapy; subsequently, liver and peritoneal metastases disappeared. However, lung metastasis was detected later, and weekly paclitaxel(PTX)combined with ramucirumab(RAM)chemotherapy was initiated; subsequently, lung metastasis and advanced gastric cancer disappeared. During remission, lung metastasis was detected again. Although weekly PTX combined with RAM chemotherapy was reinitiated, a progressive disease status was achieved. As tertiary chemotherapy, nivolumab therapy(240 mg/body, every 2 weeks)was initiated for 20 courses over 11 months. This therapy was significantly effective, which aid the patient to achieve a complete response. The patient survived and is healthy for 5 years due to chemotherapy administration alone.

A 74-year-old man presented to our hospital because of anorexia. Upper gastrointestinal endoscopy revealed type 3 gastric cancer. Further examination disclosed metastasis to the perigastric lymph nodes and to the liver, and a diagnosis of non- resectable advanced gastric cancer(cT4N2H1P0M0)in cStage Ⅳ was made. A total of 4 courses of S-1 plus oxaliplatin therapy(80 mg/body/day and 100 mg/m2/cycle, respectively, for 2 weeks followed by a 1-week rest)were administered as the primary chemotherapy. Then, another metastasis to the abdominal lymph nodes and increased liver metastasis were found; thus, the patient's condition was rated as progressive disease(PD). Secondary chemotherapy comprising 10 courses of weekly nab-paclitaxel(nab-PTX)plus ramucirumab(RAM)therapy(100 mg/m2 on days 1, 8, and 15 and 8 mg/kg on days 1 and 15, respectively, every 4 weeks)were administered. Although temporary reductions in the perigastric lymph node metastasis and liver metastasis as compared with the baseline were observed, another metastasis to the abdominal lymph nodes occurred subsequently, resulting in PD. As tertiary chemotherapy, nivolumab therapy(240 mg/body, every 3 weeks) was repeated up to a total of 30 courses over 13 months. This therapy was markedly effective, achieving a near complete response. The patient is currently being followed up as an outpatient.

A male patient in his 80s, diagnosed with rectal cancer, underwent transverse colon resection(pT3, pN0, cM0, and pStage Ⅱa, RAS wild-type, BRAF-mutant). However, 19 months later, intraperitoneal metastasis was detected and the patient received 8 courses of mFOLFOX6 plus bevacizumab. Following the observation of an allergic reaction that was attributable to oxaliplatin, the regimen was changed to a total of 7 courses of sLV5FU2 plus bevacizumab. Subsequently, a marked decrease was observed in intraperitoneal metastasis. The patient completed sLV5FU2 plus bevacizumab chemotherapy. At 1 year after the marked decrease, the metastatic recurrence was not exacerbated.

A 76-year-old female patient was diagnosed with inoperable gastric cancer with distant lymph node metastasis(cT3N2M1 [LYM], cStage Ⅳ), for which she received S-1 chemotherapy(orally administered on days 1-14 ofa 28-day courses). The patient received a total of4 2 treatment courses. After an initial phase of stable disease due to chemotherapy, she eventually showed progressive disease. S-1 chemotherapy was discontinued. Because ofher social background, she decided against any further chemotherapy. After 1 year, she underwent metallic stent insertion through the gastric cancer, which enabled her to consume food. She is currently alive as of 5 years and 3 months from the date of first diagnosis.

A 63-year-old man diagnosed with a perforated gastric ulcer and generalized peritonitis underwent surgical intervention. However, computed tomography(CT), esophagogastroduodenoscopy(EGD), and positron emission tomography-CT(PETCT) revealed an inoperable gastric cancer with liver and peritoneal metastases(cT4NxH1P1M0, cStage Ⅳ, for which he received S-1 and oxaliplatin chemotherapy[SOX therapy]). The patient underwent 10 SOX therapy cycles. Following the initial chemotherapy course, the peritoneal and liver metastases disappeared on radiographic images. However, lung metastasis was detected, and the patient initiated weekly paclitaxel(PTX)and ramucirumab(RAM)chemotherapy. After 4 treatment cycles, lung metastasis and gastric cancer disappeared.

A patient in his 70s was diagnosed with sigmoid colon cancer[pT3pN1cM1(PUL1), pStage IV ]for which he underwent sigmoid colectomy and received S-1 adjuvant therapy for the lung metastases. The patient received a total of 10 courses of S- 1, administered orally on days 1-14 of a 21-day cycle. The lung metastases showed a complete response, and the patient completed the S-1 chemotherapy. No recurrence of lung metastases was detected up to 6 months later.

In lung tumors, the association between carcinoids and high-grade neuroendocrine tumors (HGNETs) is controversial. To understand the phenotypic similarities/differences between lung carcinoids and HGNETs, we comparatively investigated the expression of three kinds of developing neural transcription factors (DNTFs: BRN2, TTF1 and ASCL1) and multiple endocrine neoplasia type 1 (MEN1) as well as RB1 and P53 using 18 carcinoids and 16 HGNETs. The DNTFs were expressed in 10 of the 18 carcinoids and in all the HGNETs, while normal neuroendocrine cells, which are considered the major cell origin of lung carcinoids and small cell carcinomas, did not express DNTFs. Both the DNTF(-) and DNTF(+) carcinoids contained typical and atypical carcinoids. All the DNTF(-) carcinoids examined were formed in the bronchial wall. All the MEN1(-) carcinoids examined were classified into the DNTF(-) carcinoids, while all the HGNETs expressed MEN1. This finding suggests that DNTF(-) MEN1(-) carcinoids are unlikely to be precursors of HGNETs. Although the status of RB1 and P53 between carcinoids and HGNETs were apparently different, the DNTF(+) carcinoids of two male patients and one female patient revealed morphologies resembling HGNET cells and relatively high Ki67 indices. Further investigation of DNTF expression in carcinoids might provide important clues to understand the association between carcinoids and HGNETs.

Patients with mediastinal lymph node metastasis (N2) in squamous cell carcinoma (SqCC) of the lung have poor prognosis after surgical resection of the primary tumor. The aim of this study was to clarify predictive factors of the recurrence of pathological lung SqCC with N2 focusing on the biological characteristics of both cancer cells and cancer-associated fibroblasts (CAFs) in primary and metastatic lymph node tumors. We selected 64 patients with pathological primary lung N2 SqCC who underwent surgical complete resection and investigated the expressions of four epithelial–mesenchymal transition-related markers (caveolin, clusterin, E-cadherin, ZEB2), three cancer stem cell-related markers (ALDH-1, CD44 variant6, podoplanin) of cancer cells, and four markers of CAFs (caveolin, CD90, clusterin, podoplanin) in both primary and matched metastatic lymph node tumors in the N2 area. In the primary tumors, the expressions of all the examined molecules were not related to recurrence. However, in the metastatic lymph node tumors, high clusterin and ZEB2 expressions in the cancer cells and high podoplanin expression in the CAFs were significantly correlated with recurrence (P = 0.03, 0.04, and 0.007, respectively). In a multivariate analysis, only podoplanin expression in the CAFs in metastatic lymph node tumors was identified as a significantly independent predictive factor of recurrence (P = 0.03). Our study indicated that the immunophenotypes of both cancer cells and CAFs in metastatic lymph node tumors, but not primary tumors, provide useful information for predicting the recurrence of pathological N2 lung SqCC.

To examine cytokine production in response to RSV infection, we assessed the levels of 29 cytokines released from RSV-infected human foetal lung fibroblasts. We also examined the relationships between the effects of fluticasone propionate and various signalling pathways in the cells. Twenty-four hours after infection (1MOI), RSV-infected cells released cytokines, for example proinflammatory cytokines (IL-1β, IL-6 and TNF-α), anti-inflammatory (IL-1ra), Th1 (IFN-γ, IFN-λ1a, IL-2 and IL-12), Th2 (IL-4, IL-5, IL-10 and IL-13), granulopoiesis-inducing (G-CSF and GM-CSF), eosinophil recruitment-inducing (eotaxin and RANTES) and neutrophil recruitment-inducing cytokines (IL-8, IP-10, MCP-1 and MIP-1α). Aberrant release of most was significantly suppressed by fluticasone propionate. Twelve hours after RSV infection, increased phosphorylation of Akt, p38 MAPK, ERK1/2 and IκB-α was noted. Fluticasone propionate suppressed the phosphorylation of Akt, p38 MAPK, and ERK1/2, but not IκB-α, in virus-infected cells. TLR-4 expression was unchanged in control and RSV-infected cells, and TLR-3 and RIG-I expression was not detected. The results indicate that RSV infection induces aberrant production and release of certain cytokines through these signalling pathways in human lung fibroblasts. Overproduction and imbalance of these cytokines may be associated with the pathophysiology of RSV-induced excessive and allergic inflammation.

Computed tomography-guided percutaneous transthoracic needle biopsy (CTNB) of the lung is a well-established diagnostic technique for the evaluation of thoracic lesions. At our institution, we have performed real-time CTNB using automated biopsy needles since 1998 and we introduced immediate cytology in 2004. We evaluate immediate cytology in CTNB to increase the diagnostic accuracy and to reduce the number of inadequate specimens. We retrospectively reviewed a consecutive series of 270 patients (group A: 98 patients before introduction, group B: 172 patients after introduction) who underwent CTNB between 2002 and 2009. We compared the diagnostic performance and the complication rates between two groups. There were no significant differences between groups A and B in patient and lesion characteristics. The rates of one time biopsy were significantly different: 56.1% (55/98) in group A and 69.2% (119/172) in group B. The rates of diagnostic accuracy in groups A and B were 79.6% (78/98) and 94.8% (163/172), respectively; the sensitivity were 74.0% (57/77) and 94.1% (127/135); the specificity were 100% (21/21) and 97.3% (36/37); the rates of major complications were 14.3% (14/98) and 2.9% (5/172). Group B had significantly higher diagnostic accuracy, sensitivity, and a lower complication rate in comparison with group A. CTNB with immediate cytology can improve diagnostic performance and decrease the complication rate. These improvements may help make CTNB less of a burden for patients. Diagn. Cytopathol. 2013;41:1063–1068. © 2012 Wiley Periodicals, Inc.

Two cases of rheumatoid nodules evaluated by fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and video-assisted thoracic surgery (VATS) biopsy are reported. The first case was that of a 44-year-old woman who presented with a cavitated nodule with intense standardized uptake values (SUVs) both in the early (max 3.4) and delayed (max 4.4) phases, suggesting malignancy. However, after VATS biopsy, she was diagnosed as having a rheumatoid nodule with vasculitis. The second case was that of a 74-year-old woman admitted with bilateral lung nodules, two of which showed intense early (max 2.2) and delayed (max 6.0) phase SUVs, and mild early (max 0.6) and delayed (max 0.9) phase SUVs. These two nodules were finally proven to be a lung cancer and rheumatoid nodule without vasculitis, respectively. These cases show that rheumatoid nodules with an enhanced inflammatory process, such as vasculitis, can appear false-positive for malignancy on FDG-PET/CT scan images.

Background Signaling mediated by hepatocyte growth factor (HGF)/MET promotes multiple biological activities, including cell proliferation, motility, invasion, angiogenesis, and morphogenesis. Overexpression of HGF and MET and an increase of the MET gene copy number have recently been found in various cancers that had a poor outcome. Here we investigated the copy number of the MET gene and expression of MET and HGF in small pulmonary adenocarcinomas. Methods Tumor tissues were obtained from 106 pulmonary small adenocarcinomas 2cm or less in diameter. MET gene copy number, and the expression of MET and HGF, were analyzed using fluorescence in situ hybridization (FISH) and immunohistochemistry, respectively. Results MET FISH-positive signals were observed in 11 (10.4%) of 106 cases. One case (0.9%) showed gene amplification and 10 (9.4%) exhibited high polysomy. High immunoreactivity for MET and HGF in tumor cells was found in 30 (28.3%) and 19 cases (17.9%), respectively. HGF was also expressed in stromal cells in 32 cases (30.2%). No cases of non-invasive adenocarcinoma (adenocarcinoma in situ , localized bronchioloalveolar carcinoma) showed MET FISH-positive signals or high expression of HGF in the tumor cells. Expression of both MET and stromal HGF was stronger in invasive than in non-invasive adenocarcinoma. MET FISH-positive signals and high immunoreactivity for MET and HGF in tumor cells were associated with factors indicative of poor prognosis such as pleural invasion, vascular invasion, lymphatic permeation, lymph node metastasis, and nuclear grading. Univariate and multivariate analyses that included these factors showed that all statuses except for MET and HGF immunoreactivity were significantly associated with an increased risk of death. However, multivariate analysis revealed no independent factors related to poor prognosis. Conclusion Our results suggest that abnormality of the HGF/MET pathway occurs during the course of progression from non-invasive to invasive pulmonary adenocarcinoma. An increased MET gene copy number is indicative of a poor outcome in patients with small pulmonary adenocarcinomas.

Background Systemic chemotherapy remains the standard treatment for metastatic transitional cell carcinoma (TCC) of the urinary tract. For pulmonary metastases of several malignancies, surgical therapy for selected patients has become a treatment of choice to achieve cure. However, data on pulmonary metastasectomy for urinary TCC remain limited. Methods From 1990 to 2005, 2,288 patients who underwent pulmonary metastasectomy for all types of malignancy were registered in the Metastatic Lung Tumor Study Group of Japan. Of these, we extracted 32 patients with TCC who underwent pulmonary metastasectomy with a curative intent from the database. We investigated the surgical outcomes of the patients, focusing on long-term progression-free survival (PFS) and modified PFS as a parameter for achieving a cure. In modified PFS, when the disease-free status had continued for longer than two years after repeated resection at the last follow-up, the first recurrence was not considered as an event. Results The five-year overall survival and PFS rates were 50% and 26%, respectively. Including 3 patients who underwent a second pulmonary metastasectomy for recurrence, 9 patients survived without recurrence for more than 5 years, resulting in a modified five-year PFS rate of 40%. Multivariate analysis revealed that a pulmonary metastasis greater than 3 cm was a significantly poor prognostic factor. The modified five-year PFS rate for patients with a pulmonary metastasis smaller than 3 cm in diameter was 65%. Conclusions Pulmonary metastasectomy may have a curative role in the treatment of metastatic TCC in appropriately selected patients, especially those with a small solitary pulmonary metastasis.

Introduction: Understanding the mechanisms of drug resistance to epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) is essential to develop novel chemotherapies for non-small cell lung cancer (NSCLC). Therefore, we analyzed the expression and function of ATP-binding cassette (ABC) transporters in EGFR TKI-resistant NSCLC. Methods: In three newly established AG1478-resistant NSCLC cell lines, we evaluated the expression profile of ABC transporters and genotyping of ABCG2 by real-time polymerase chain reaction and elucidated their function by Hoechst dye efflux analyses. The growth-inhibitory effect of the topoisomerase I inhibitor Hoechst 33342, which is extruded by ABCG2, was also investigated in these cells using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay. Results: In AG1478-resistant cells, significantly less ABCG2 was expressed, and the ratios of the cells with a strong ability to extrude Hoechst dye were remarkably smaller than in the parent cells. Because of the ABCG2 downregulation and loss of function due to C421A/C421A homozygosity, PC-14AG50R was thus considered to be more sensitive to Hoechst 33342 than the parental cells. All AG1478-resistant cells were more sensitive to the combination of Hoechst 33342 and AG1478 than to single agent. Conclusions: Resistance to EGFR TKI in NSCLC is associated with the downregulation of ABCG2 expression. A topoisomerase I inhibitor alone or in combination with EGFR TKI might offer a promising strategy for treating NSCLC that is resistant to EGFR TKI.

BACKGROUND: According to the World Health Organization Classification of Tumors, the prognostic value of morphometric cytologic atypia has not been assessed in pulmonary adenocarcinoma. METHODS: Primary tumors of 133 pulmonary adenocarcinomas ≤2 cm were analyzed using an image processor for analytical pathology. The results were evaluated using receiver operator characteristic curve analysis, and survival curves were drawn by the Kaplan-Meier method. Furthermore, the results were applied to routine histological diagnosis. Four pathologists evaluated the nuclear factors relative to the size of small lymphocytes as a standard. RESULTS: By using the nuclear area and nuclear major axis dimension, lung adenocarcinomas were divisible into 2 groups showing extremely favorable prognosis and fairly favorable prognosis, without considering histological features or classification. A nuclear area level of

症例はアスベスト曝露歴のない55歳の女性．人間ドックでCTを撮影したところ右肺尖部に腫瘤影を指摘され肺癌の疑いで当科を紹介された．術中針生検で採取した標本は虚脱した肺組織であったが，確定診断のため右S1区域切除を施行した．永久標本では肺組織の虚脱と間質への炎症細胞浸潤を認め，胸膜が肥厚し一部に硝子化を認めたため円形無気肺と診断した．文献的に上葉の円形無気肺は極めてまれであり，診断に苦慮した1例を経験したので報告した．

目的．本邦における2002年の肺癌治療成績を明らかにする．方法．肺癌登録合同委員会は，初診が2002年であった原発性肺癌を対象として登録を行い，2004年，2009年に追跡した．358施設から18,552例の登録がなされたが，生存期間の判明した14,695例を検討した．結果．男女比は2：1，平均年齢は67.1歳，分布は，組織型は腺癌が56.7%，扁平上皮癌が25.7%，小細胞癌が9.2%，臨床病期はIA期29.3%，IB期15.3%，IIA期1.4%，IIB期6.2%，IIIA期11.6%，IIIB期14.4%，IV期20.7%，手術あり症例は57.5%，手術なし症例は39.0%であった．5年生存率は，全組織型で44.3%，小細胞癌で14.7%，非小細胞癌で46.8%，手術あり症例，手術なし症例で，それぞれ66.0%，8.5%，男性，女性でそれぞれ37.7%，59.0%であった．臨床病期別では小細胞癌，非小細胞癌それぞれ，IA期（52.7%，79.4%），IB期（39.3%，56.9%），IIA期（31.7%，49.0%），IIB期（29.9%，42.3%），IIIA期（17.2%，30.9%），IIIB期（12.4%，16.7%），IV期（3.8%，5.8%）であった．結論．2002年の本邦における肺癌治療例は，腺癌が最も多く扁平上皮癌，小細胞癌が続いた．予後は5年の経過で，女性が男性より良く，非小細胞癌が小細胞癌より良く，手術あり症例が手術なし症例より良好であった．これらの差が生じている要因についてはさらなる検討を要する．

背景．小細胞肺癌に伴う傍腫瘍小脳変性症の報告は近年増加傾向にあるが，同様の症例に対して手術を施行した報告は少なく，手術後の腫瘍随伴症状の変化に対する報告はない．症例．56歳男性．2009年2月より徐々に浮動性めまい，歩行障害，嘔気，ろれつ障害が増悪し，当院神経内科を受診し，小脳失調と診断された．精査により右肺中葉の結節影を認め，気管支鏡検査で小細胞癌の診断であった．リンパ節転移及び遠隔転移は認めなかった．血清，及び脳脊髄液中抗Hu抗体陽性であり，傍腫瘍小脳変性症及び小細胞肺癌（cT1N0M0 stage IA）と診断した．右中葉切除及び2群リンパ節郭清を施行したが（pT1N2M0 stage IIIA），術後1ヶ月間は神経症状の改善を認めなかった．その後免疫グロブリン大量投与療法及び補助化学療法（CDDP+VP-16）を施行し，免疫グロブリン療法開始後から軽度の神経症状の改善を認めたが完全な改善には至らなかった．結論．傍腫瘍小脳変性症を合併した小細胞肺癌の治療例を経験した．完全切除を行ったが，神経症状の改善を速やかには認めなかった．術後，免疫グロブリン投与及び補助化学療法を追加し若干の改善を認めた．

BackgroundIn 1986, Japanese Association for Thoracic Surgery started a nationwide survey of the number of primary lung cancer undergoing resection and this survey was continued annually. Thereafter, investigations of lung cancer surgical results have been conducted three times. The postoperative overall 5-year survival rate was 47.8% in resected cases in 1989, 52.3% in 1994, and 62.0% in 1999, showing improvement over the decade (p < 0.01).ObjectiveTo clarify the factors influencing survival improvements retrospectively.Patients and MethodsThe subjects of the investigation are the patients who underwent resection for primary lung cancers in 1989, 1994, and 1999. Postoperatively, after 5 years, surveys of surgical results were sent to institutes where lung cancer resection had been performed. The subjects undergoing resection who provided 10 items (age, sex, pathologic T factor, pathologic N factor, pathologic M factor, date of resection, histology, curability, prognosis, and survival time) numbered 3004 in 1989, 6895 in 1994, and 12,235 in 1999. They were classified according to the Union International Contre le Cancer 1997 revised tumor, node, and metastasis classification. Differences in age, gender, histology, pathologic stage, curability, and operative death rates were analyzed for each survey year.ResultsAccording to the changes in proportions, the cases over 70 years of age, women, and pathologic stage I increased significantly (p < 0.001), whereas in cases with small cell lung cancer, incomplete resection and operative death decreased significantly over time (p < 0.001).ConclusionThe postoperative 5-year survival rate in Japan improved between 1989 and 1999. The main cause of this improvement was the increase in early stage lung cancer, especially cases with tumors 2 cm or less in size.

To determine the usefulness of positron emission tomography (PET) with (11)C-acetate (AC) for imaging lung adenocarcinoma and evaluating its tumor aggressiveness, AC- and (18)F-fluorodeoxyglucose (FDG)-PET were compared.One hundred and sixty-nine adenocarcinomas with clinical stage IA and 53 benign nodules were examined by both AC- and FDG-PET before surgery. The sensitivity and specificity for discriminating benign/adenocarcinoma were compared between AC- and FDG-PET. The AC and FDG uptakes were examined to determine the relationship with tumor aggressiveness, i.e., pathological tumor stage, lymphatic, vascular, or pleural involvement, and proliferative activity determined by Ki-67 staining score.While the sensitivity of AC-PET was significantly higher than FDG-PET for bronchioloalveolar carcinoma (BAC) and well-differentiated (W/D) adenocarcinoma (p0.001 and 0.006, respectively), there was no significant difference for moderately or poorly differentiated adenocarcinoma. The specificity was not different between them. While FDG uptakes were significantly higher in tumors with pathological advanced stages or those with lymphatic, vascular and/or pleural involvements than in tumors with pathological stage IA or those without these tumor involvements (p = 0.04 to p0.001), AC uptake did not show significant differences between the respective sub-groups except according to the tumor stage. While both AC and FDG uptakes showed a significant correlation with Ki-67 staining scores (p = 0.03 and p0.001, respectively), the correlation coefficient of former was lower than that of latter (p = 0.07).While AC-PET can image BAC and W/D adenocarcinoma with a higher sensitivity than FDG-PET, it cannot evaluate tumor aggressiveness of clinical stage IA lung adenocarcinoma as well as FDG-PET.

BACKGROUND: 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. METHODS: Forty thymomas were examined using both FDG-PET and AC-PET before surgery. The histologic types were type A in 1 thymoma, type AB in 12 thymomas, type B1 in 11 thymomas, type B2 in 7 thymomas, type B3 in 6 thymomas, and type C in 3 thymomas. Tumor invasiveness was assessed by pathologic tumor stage and was identified as stage I in 17 tumors, stage II in 17 tumors, stage III in 4 tumors, and stage IV in 2 tumors. FDG and AC uptake was measured as the maximum standard uptake value (SUV). RESULTS: The FDG-SUV in type C thymomas was significantly higher than that in the other types (A-B3; P = .001 – P = .048). The AC-SUV in type A/AB thymomas was significantly higher than that in the other tumor types (B1-C; P < .001 – P = .002). All 3 type C tumors had an FDG-SUV ≥6.3, and all 13 type A/AB tumors had an FDG-SUV

The purpose of the present study was to retrospectively analyze the clinicopathological characteristics and clarify the validity of surgical resection for patients with positive pleural lavage cytology (PLC). Between 1993 and 2006, 563 patients who underwent complete surgical resection for primary non-small cell lung cancer and who were examined with regard to PLC were retrospectively analyzed. Forty-two patients (7.2%) showed positive PLC. The 5-year survival rates were 65.0% and 33.5% for patients with negative and positive PLC, respectively. The 5-year survival rates for patients with positive PLC were 57.1%, 50.8%, 40.0%, and 0% for pathological stage I, II, IIIA, and IIIB, respectively. Multivariate analysis revealed that preoperative carcinoembryonic antigen (CEA) level, PLC, vascular invasion, lymphatic permeation, and pathological stage were independent prognostic factors. The 5-year survival rate for the patients with a high CEA level and positive PLC was 0%. Intrathoracic recurrence was observed more frequently in patients with positive PLC. PLC was an independent prognostic factor. While positive PLC alone may not be a contraindication for surgical resection, patients who are complicated with a high CEA level preoperatively should receive special attention since no long-term survivors were observed.

Objective Magnetic resonance imaging (MRI) with various technologic advancements has generally been used to elevate the accuracy of diagnosis for several malignant tumors. This study retrospectively evaluated the efficacy of newer MRI techniques for differentiating among the different types of invasiveness in lung adenocarcinoma by comparing the MRI findings with the pathologic findings. Materials and methods From May 2005 to April 2007, 46 patients with lung adenocarcinoma measuring 3 cm or less across the greatest dimension underwent a surgical operation including preoperative MRI study in this hospital. The MR imaging protocol included 3 pulse sequences: (1) respiratory-triggered T2-weighted short TI inversion recovery; (2) respiratory-triggered high b-value diffusion-weighted imaging (DWI); (3) gadolinium-enhanced dynamic MRI studies. Results Of all the tumors, 13 were bronchioloalveolar carcinoma (BAC), 24 were adenocarcinomas with mixed subtypes (advanced BAC), and 9 were other histologic subtypes (non-BAC). Both the moderate and strong signal intensity on DWI was significantly greater in the advanced BAC (79.2%) and the non-BAC (88.9%) than in the BAC (38.5%). In the dynamic study, a strong enhancement on the time-intensity curve was significantly greater in the advanced BAC (95.2%) and the non-BAC (87.5%) than in the BAC (25%). When the lesions demonstrated a strong enhancement in dynamic study or showed strong signal intensity on DWI, they were judged to be positive. Sensitivity, specificity, and accuracy were 97%, 76.9%, and 91.3%, respectively. Conclusions DWI could therefore be a useful diagnostic modality for differentiating the subtypes of lung adenocarcinomas, and the MRI finding may thus provide useful supplementary information before surgery comprising limited resections.

目的．末梢型の小型肺腺癌を対象として，MRI拡散強調画像の画像解析と切除標本の病理学的な所見とを対比しその有用性を検討した．対象と方法．2005年5月から2007年12月までに当センターで手術を施行した，病理学的な腫瘍長径が2 cm以下の小型肺腺癌38例を対象とした．対象症例を，Noguchi分類のType A+Bを非浸潤癌（n=12），Type Cを初期浸潤癌（n=21），Type D+Eを浸潤癌（n=5）と定義した．病巣部の信号強度（DWI）を脊髄部の信号強度（SC）で割ることでえられた比率（DWI/SC比）を算出した．CTとDWI/SC比の画像解析データをもとにROC（receiver operating characteristic）曲線を作成し比較検討した．結果．各浸潤度別のDWI/SC比（平均値）は非浸潤癌が0.444±0.283，初期浸潤癌が0.985±0.513，浸潤癌が0.790±0.344であった．非浸潤癌と初期浸潤癌（p=0.0021），非浸潤癌と浸潤癌（p=0.0468）との間で有意差を認めた．DWI/SC比は比較的にROC曲線が左肩上がりの傾向を示し，より安定的な結果となった．結論．肺野末梢型の小型肺腺癌に対する高b値拡散強調画像は病変の悪性度（浸潤度）を見極めるのに有用であり，そして近い将来縮小手術の適応など治療方針の決定に関わる付加的な情報を提供するものと思われる．