Liver metastases 2 years after resection of a very-low-risk duodenal gastrointestinal stromal tumor: a case report.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are rare mesenchymal tumors, but are the most common mesenchymal tumors of the gastrointestinal tract. The risk classification of GISTs is based on the tumor size, mitotic index, tumor site, and presence of tumor rupture. Recurrence in the very-low-risk group is extremely rare. We herein report a case of liver metastases 2 years after resection of a very-low-risk duodenal GIST. CASE PRESENTATION: A 57-year-old woman presented to the hospital for evaluation of melena. Esophagogastroduodenoscopy showed bleeding from the exposed blood vessels at the top of a submucosal tumor approximately 20 mm in size located in the second (descending) part of the duodenum, and the bleeding was controlled with electrocoagulation. A GIST was suspected, and the patient underwent wedge resection of the duodenum. The resected specimen contained a 16- × 12-mm (< 20-mm) white submucosal tumor composed of spindle cells with a mitotic count of 4 per 50 high-power fields, and a histologically negative margin was achieved. Immunochemical analysis revealed positive tumor staining for c-kit protein and alpha-smooth muscle actin and negative staining for CD34, desmin, and S-100 protein. Therefore, the tumor was diagnosed as a very-low-risk duodenal GIST based on the Fletcher classification and modified Fletcher classification (Joensuu classification). The postoperative course was uneventful, and the patient was discharged on postoperative day 11. At the follow-up visit 2 years postoperatively, contrast-enhanced computed tomography revealed liver tumors in S8 and S6 measuring 26 × 24 and 10 × 10 mm, respectively. Both lesions showed peripheral dominant hyperenhancement with hypoenhancement inside, indicating tissue degeneration within the tumors. These imaging findings closely resembled those of the duodenal GIST. Hence, the patient was diagnosed with liver metastases of GIST 2 years postoperatively. She was subsequently started on treatment with 400 mg of imatinib. At the time of this writing (2 months after diagnosis), the patient was clinically well and asymptomatic and was continuing imatinib therapy. CONCLUSIONS: Recurrence of very-low-risk GISTs is extremely rare. Even a small GIST with low mitotic activity can never be considered completely benign, and long-term follow-up is necessary.

Prognostic value of postoperative decrease in serum albumin on surgically resected early-stage non-small cell lung carcinoma: A multicenter retrospective study.

BACKGROUND: Preoperative nutritional status is an important host-related prognostic factor for non-small cell lung carcinoma (NSCLC); however, the significance of postoperative changes in nutritional status remains unclear. This study aimed to elucidate the significance of postoperative decreases in serum albumin (ΔAlb) on the outcomes of early-stage NSCLC. METHODS: We analyzed 443 training cohort (TC) and 642 validation cohort (VC) patients with pStage IA NSCLC who underwent surgery and did not recur within 1 year. We measured preoperative serum albumin levels (preAlb) and postoperative levels 1 year after surgery (postAlb), and calculated ΔAlb as (preAlb - postAlb)/preAlb × 100%. A cutoff value of 11% for ΔAlb was defined on the basis of the receiver operating characteristic curve for the TC. RESULTS: Patients were divided into ΔAlb-Decreased and ΔAlb-Stable groups, including 100 (22.6%) and 343 (77.4%) in the TC, and 58 (9.0%) and 584 (90.1%) in the VC. ΔAlb-Decreased was associated with male sex (p = 0.0490), smoking (p = 0.0156), and non-adenocarcinoma (p<0.0001) in the TC, and pT1b (p = 0.0169) and non-adenocarcinoma (p = 0.0251) in the VC. Multivariable analysis identified ΔAlb as an independent prognostic factor for disease-free survival (DFS) and overall survival (OS) in both cohorts (VC: DFS, HR = 1.9, 95%CI: 1.10-3.15, p = 0.0197; OS, HR = 2.0, 95%CI: 1.13-3.45, p = 0.0173). Moreover, subgroup analysis demonstrated that the prognostic value of ΔAlb was consistent for age, sex, smoking history, surgical procedure, and histological type. CONCLUSION: We demonstrated a negative impact of postoperative decrease of the serum albumin on the prognosis of patients with early-stage NSCLC. Postoperative changes in nutritional status might be important in NSCLC outcomes.

First-line osimertinib for leptomeningeal metastasis from lung adenocarcinoma with EGFR mutation as the initial and solitary site of postoperative recurrence.

Leptomeningeal metastasis (LM) from lung cancer has poor prognosis, and effective therapy has not been established. We present the case of a 54-year-old man with LM from lung adenocarcinoma harboring EGFR L858R point mutation, who received osimertinib as first-line therapy. He had previously undergone left lower lobectomy and lymph node dissection for lung adenocarcinoma. Five years and 9 months after the operation, he developed symptoms of dizziness, lightheadedness, and headache. Magnetic resonance imaging showed high signal intensity in the cerebral sulcus and meninges, and cerebrospinal fluid (CSF) cytology indicated adenocarcinoma with EGFR L858R point mutation, which suggested LM. After CSF drainage and administration of corticosteroid and glycerol, the patient received osimertinib (80 mg/day) as first-line therapy. These symptoms including dizziness, lightheadedness, and headache were relieved and the MRI appearance was normal, and he survived for 19 months with no disease progression. Osimertinib is considered to be an effective therapeutic option for LM from lung adenocarcinoma harboring EGFR mutation.

Radiologic Features of Resected Lung Adenocarcinoma With Epithelial-Mesenchymal Transition.

BACKGROUND: Epithelial-mesenchymal transition plays a crucial role in cancer progression and is a significant prognosticator for postoperative survival in patients with lung cancer. Predicting epithelial-mesenchymal transition preoperatively using computed tomography may help to determine the optimal surgical strategy. METHODS: We performed an immunohistochemical analysis of E-cadherin and vimentin expressions using tumor specimens from resected primary lung adenocarcinoma and classified the results into 3 subgroups according to the expressions: epithelial, intermediate, and mesenchymal. The intermediate and mesenchymal groups were classified as the epithelial-mesenchymal transition conversion group. We analyzed the association between epithelial-mesenchymal transition and radiologic characteristics, especially computed tomographic features. RESULTS: The epithelial-mesenchymal transition conversion group comprised 162 patients (49.1%). Computed tomography revealed that tumors with epithelial-mesenchymal transition conversion showed a high consolidation/tumor ratio compared with those without conversion. Univariate analysis demonstrated that tumors with epithelial-mesenchymal transition were significantly associated with bronchial and/or vascular convergence (P < .001) and notching (P = .028). When the cutoff value for the consolidation/tumor ratio was set by the receiver operating characteristic curve, independent predictive factors for epithelial-mesenchymal transition by multivariate analysis were high ratio (>0.7946; P < .001) and the presence of convergence (P = .05). Tumors with a high consolidation/tumor ratio and convergence had a 4-fold higher odds ratio for epithelial-mesenchymal transition, and patients had significantly poorer survival. CONCLUSIONS: Convergence and a high consolidation/tumor ratio were independently associated with epithelial-mesenchymal transition conversion. These preoperative radiologic results will help to predict epithelial-mesenchymal transition conversion in lung adenocarcinoma.

Interleukin-38 promotes tumor growth through regulation of CD8+ tumor-infiltrating lymphocytes in lung cancer tumor microenvironment.

BACKGROUND: Interleukin (IL)-38 was discovered in 2001 and is a member of the IL-1 family of cytokines. IL-38 shows anti-inflammatory activity in several inflammatory diseases. In lung adenocarcinoma, we previously demonstrated that high IL-38 expression in tumor cells was associated with poor prognosis. However, the role of IL-38 in the tumor microenvironment has not been clarified. METHODS: IL-38-plasmid-transfected Lewis lung carcinoma cells (LLC-IL38) and empty vector-transfected LLC cells (LLC-vector) were established. Cell proliferation in vitro and tumor growth in vivo were examined, and immunohistochemical staining was used to assess tumor-infiltrating lymphocytes (TILs). A CD8+ lymphocyte depletion model was established to show the association between IL-38 and CD8+ lymphocytes. Moreover, we examined the association between IL-38 expression and CD8+ TILs in human samples, analyzing immunohistochemical staining in 226 patients with radically resected lung adenocarcinoma. RESULTS: Tumor growth of LLC-IL38 in vivo was significantly increased compared with that of LLC-vector, although cell proliferation of LLC-IL38 in vitro was lower than that of LLC-vector. CD8+ TILs were significantly decreased in LLC-IL38 tumor compared with LLC-vector tumor. The difference in tumor growth between LLC-IL38 and LLC-vector became insignificant after depletion of CD8+ lymphocytes. In immunohistochemical staining in tissues from patients with lung adenocarcinoma, multivariate analysis showed high IL-38 expression was an independent negative predicter of high density of CD8+ TILs. CONCLUSION: We demonstrated that high IL-38 expression in tumor cells was significantly associated with reduction of CD8+ TILs and tumor progression. These results suggest that IL-38 could be a therapeutic target for lung cancer.

Clinical significance of preoperative inflammatory markers in non-small cell lung cancer patients: A multicenter retrospective study.

Inflammatory biomarkers have been associated with clinical outcomes in non-small cell lung cancer (NSCLC). However, the best prognostic marker(s) has not been identified, and the association between inflammatory markers and clinical characteristics is poorly understood. We selected 1,237 patients with resected NSCLC from Kyushu University (2003-2015) and Kyushu Cancer Center (2009-2015) in Japan. Pearson product-moment correlation coefficient among inflammatory markers and area under curve (AUC) of receiver operating characteristic (ROC) curve analyses for overall survival (OS) were calculated. We analyzed the associations between inflammatory markers and clinical factors using Student's t-test. Univariate and multivariate analyses with Cox proportional hazards regression analyses were performed to evaluate the relationship between survival and clinical factors. The cut-off values for neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR), platelet-lymphocyte ratio, and derived NLR (dNLR) were determined by ROC curve analyses for OS. We found a strong positive correlation between NLR and dNLR (r = 0.9629). The AUC of LMR was the highest amongst the measured metrics, and the AUC of NLR was higher than dNLR. Levels of some inflammatory markers were associated with sex, smoking, squamous cell carcinoma, and pathological stage. LMR ≥ 5.11 and lactate dehydrogenase (LDH) concentration ≥ 222 (U/L) were independent predictors of both disease-free survival (DFS) and OS (LMR; P = 0.0009 and 0.0008, LDH; P = 0.0195 and 0.0187, respectively). Certain inflammatory markers, potentially linked to smoking, were associated with an advanced pathological stage in NSCLC. LMR and LDH were independent predictors of both DFS and OS.

Expression of PD-L1, PD-L2, and IDO1 on tumor cells and density of CD8-positive tumor-infiltrating lymphocytes in early-stage lung adenocarcinoma according to histological subtype.

PURPOSE: This study examined the expression of programmed cell death-ligand 1 (PD-L1), programmed cell death-ligand 2 (PD-L2), and indoleamine 2,3-dioxygenase-1 (IDO1) in tumor cells and cluster of differentiation 8 (CD8)-positive tumor-infiltrating lymphocytes (TILs) in early-stage lung adenocarcinoma according to histological subtypes. METHODS: We evaluated PD-L1, PD-L2, and IDO1 expression in tumor cells and CD8-positive TILs in surgically resected specimens from 196 stage 0 or I lung adenocarcinoma patients by immunohistochemical staining. We also examined the relationships between the expression of PD-L1, PD-L2, and IDO1 in tumor cells and the density of CD8-positive TILs and clinical factors. Patients were divided into three groups: A, adenocarcinoma in situ and minimally invasive adenocarcinoma (N = 32); B, lepidic predominant invasive adenocarcinoma (IAD; LPA; N = 66); and C, IAD except for LPA (N = 98). RESULTS: PD-L1 was expressed only in Group C, but not in Groups A or B. The positive ratio of PD-L2 was significantly higher in Group C (63.3%), and that of IDO1 was also significantly higher in Group C (65.3%). The density of CD8-positive TILs was significantly higher in Group C (45 ± 2.4). There was no significant difference between the positive ratios of PD-L2 and IDO1 and the density of CD8-positive TILs in Group A (50.0%, 21.9%, and 36 ± 4.1, respectively) or Group B (60.6%, 25.8%, and 44 ± 3.0, respectively). CONCLUSIONS: No cases in Groups A and B expressed PD-L1. The expression of immune-related factors, especially PD-L1 and IDO1, was significantly associated with Group C. This is the first report of the detailed examination of PD-L1, PD-L2, IDO1, and CD8 expression in lung adenocarcinoma subtypes with lepidic predominant components. Our results could help identify patients who would benefit from perioperative immunotherapy.

Serum markers associated with treatment response and survival in non-small cell lung cancer patients treated with anti-PD-1 therapy.

BACKGROUND: Several serum markers have been associated with treatment response and clinical outcome in non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors. MATERIALS AND METHODS: We performed univariate and multivariate analyses on 226 patients with advanced or recurrent NSCLC treated with anti-programmed cell death-1 (PD-1) therapy. The cut-off values for body mass index (BMI), albumin (Alb), and serum inflammatory markers were determined by receiver operating characteristic curve analyses. Tumor response was assessed by computed tomography according to the Response Evaluation Criteria in Solid Tumors, version 1.1. RESULTS: BMI ≥ 19.1 kg/m2 and derived neutrophil-lymphocyte ratio (dNLR) < 2.79 were independent predictors of overall response, and Alb ≥ 3.5 g/dL and dNLR < 2.79 were independent predictors of disease control. Analyses of survival revealed that Alb < 3.5 g/dL, dNLR ≥ 2.79, lymphocyte-monocyte ratio < 2.12, and red blood cell distribution width ≥ 15.9 % were independent predictors of both progression-free and overall survival. Moreover, these markers tended to have a strong impact on survival, especially among patients with programmed cell death-ligand 1 tumor proportion score ≥ 50 %. CONCLUSIONS: dNLR might be the most important factor for predicting the efficacy in NSCLC patients treated with anti-PD-1 therapy.

Rapidly Destructive Coxarthrosis as a Potential Side Effect of Crizotinib in a Patient with ROS1-Positive Lung Adenocarcinoma.

A 75-year-old woman was diagnosed with c-ros oncogene 1 (ROS1)-positive lung adenocarcinoma. She was treated with crizotinib 750 mg/day for 4.5 years, with partial tumor response. However, the patient subsequently presented with right hip pain and difficulty in walking. She underwent magnetic resonance imaging (MRI), which detected T2 prolongation in the right femoral bone head, synovial fluid retention, and bone joint fissure narrowing. The patient was diagnosed with rapidly destructive coxarthrosis (RDC) and received a total hip arthroplasty. This represents a rare case of RDC as a potential side effect of crizotinib in a patient with ROS1-positive lung adenocarcinoma. MRI should therefore be recommended in patients receiving crizotinib who experience continuing severe hip pain and difficulty in walking. Further investigations are warranted to elucidate the pathogenesis of RDC associated with crizotinib treatment.

Clinical impact of skeletal muscle area in patients with non-small cell lung cancer treated with anti-PD-1 inhibitors.

PURPOSE: The aim of this study was to elucidate the clinical impact of skeletal muscle area (SMA) in patients with non-small cell lung cancer (NSCLC) treated with anti-programmed cell death-1 (PD-1) inhibitors. METHODS: Univariate and multivariate analyses were performed on data of 103 patients with advanced or recurrent NSCLC treated with anti-PD-1 inhibitors. The SMA was measured at the level of the third lumbar vertebral (L3) on computed tomography images using OsiriX software (32-bit, version 5.8; OsiriX, Geneva, Switzerland). The L3 muscle index (cm2/m2) was defined as the SMA (cm2) at the L3 level divided by the height (m) squared. RESULTS: L3 muscle index Low was an independent predictor of both progression-free (P = 0.0399) and overall survival (P = 0.0155). Moreover, the disease control rate was significantly lower in the L3 muscle index Low group (49.0% [25/51]) than in the L3 muscle index High group (73.1% [38/52]; P = 0.0117). However, there was no significant difference between the response rates of the L3 muscle index Low group (21.6% [11/51]) and L3 muscle index High group (32.7% [17/52]; P = 0.2031). CONCLUSIONS: L3 muscle index Low is an independent predictor of worse outcomes in NSCLC patients treated with anti-PD-1 inhibitors.

Combined Evaluation of Tumor-Infiltrating CD8 + and FoxP3 + Lymphocytes Provides Accurate Prognosis in Stage IA Lung Adenocarcinoma.

BACKGROUND: Immunotherapy has become a standard treatment option for non-small cell lung cancer (NSCLC), with the tumor microenvironment attracting significant attention. CD8 + and forkhead box protein P3 + (FoxP3 +) tumor-infiltrating lymphocytes (TILs) influence the tumor microenvironment, but the clinical significance of CD8 + and FoxP3 + TILs in stage IA lung adenocarcinoma (LAD) is poorly understood. METHODS: We analyzed 203 patients with stage IA primary LAD who had undergone surgery at Kyushu University from January 2003 to December 2012. We evaluated CD8 + and FoxP3 + TILs by immunohistochemistry. We set the cutoff values at 50 cells/0.04 mm2 for CD8 + TILs and 20 cells/0.04 mm2 for FoxP3 + TILs, respectively. We divided the patients into four groups: CD8-Low/FoxP3-Low; CD8-High/FoxP3-Low; CD8-Low/FoxP3-High; and CD8-High/FoxP3-High. We compared clinical outcomes among them. Programmed cell death ligand-1 (PD-L1) expression by tumor cells was also evaluated as previously reported. RESULTS: Respectively, 104 (51.2%), 46 (22.7%), 22 (10.8%), and 31 (15.3%) patients were classified as CD8-Low/FoxP3-Low, CD8-High/FoxP3-Low, CD8-Low/FoxP3-High, and CD8-High/FoxP3-High. Both disease-free survival (DFS) and overall survival (OS) were significantly worse in the CD8-Low/FoxP3-High group than the other groups (5-year DFS: 66.3% vs. 90.5%; P = 0.0007, 5-year OS: 90.9% vs. 97.0%; P = 0.0077). In the multivariate analysis, CD8-Low/FoxP3-High and PD-L1 expression were independent prognostic factors of DFS, and lymphatic invasion, surgical procedure, and PD-L1 expression were independent prognostic factors of OS. CONCLUSIONS: CD8-Low/FoxP3-High was an independent prognostic factor of DFS (hazard ratio: 3.22; 95% confidence interval: 1.321-7.179; P = 0.0121) in stage IA LAD. Immunosuppressive conditions were associated with poor prognosis in stage IA LAD.

The Influence of Clinical T Factor on Predicting Pathologic N Factor in Resected Lung Cancer.

BACKGROUND: We investigated the utility of the clinical T factor of the 8th edition of the TNM classification, which newly defines the consolidation size of the tumor, as a valuable predictor of pathologic lymph node metastasis (pN+) and the prognosis. METHODS: We retrospectively reviewed 825 patients with surgically resected cN0 M0 non-small cell lung cancer of any T stage, focusing on the tumor's total size (7th edition) and consolidation size (8th edition) and examined pN+ and the prognosis. RESULTS: No pN+ cases in the 7th or 8th edition groups had a tumor size of less than 1 cm, and in those sized 1 to 3 cm, the frequency of pN+ in the 7th and 8th edition groups was 10.3% and 13.4%, respectively. The frequency of pN+ in tumors without ground glass opacity (GGO-) was 5.5-times higher than that of tumors with GGO (GGO+). The frequency of pN+ in the GGO+ 8th edition group was twice that in the GGO+ 7th edition group. The frequency of pN+ in the GGO- 7th edition group was 4-times higher than that of the GGO+ 7th edition group. A multivariate analysis revealed that total size exceeding 2 cm, consolidation size exceeding 2 cm, and GGO- were significant predictors of a pN+ status, indicating that a consolidation size of more than 2 cm was a stronger predictor than a total size of more than 2 cm. CONCLUSIONS: A consolidation size of more than 2 cm and GGO- were predictors of pN+, and the clinical T factor of the 8th Edition was a stronger predictor of the pN+ status than that of the 7th edition.

Serum MicroRNA-150 Predicts Prognosis for Early-Stage Non-Small Cell Lung Cancer and Promotes Tumor Cell Proliferation by Targeting Tumor Suppressor Gene SRCIN1.

This integrative multistage study was aimed to identify circulating microRNAs (miRNAs) as prognostic biomarkers and investigate the treatment target for early-stage non-small cell lung cancer (NSCLC) patients. In stage I-II NSCLC patients, we screened and validated the miRNA ratio signatures predictive of prognosis in serum. In tumor, we found that the expression of miR-150 in identified miRNA signatures was also associated with survival. Increased miR-150 expression promoted NSCLC cell proliferation and migration and vice versa. Specific mRNA cleavage sites targeted by endogenous miR-150 in 3' untranslated region (UTR) of SRCIN1 was identified by utilizing our recently developed novel Stem-Loop-Array reverse-transcription polymerase chain reaction (SLA-RT-PCR) assay. The blocking action of miR-150 resulted in repressed NSCLC cell growth in vitro and knockdown of miR-150 caused substantial tumor volume reduction in vivo. Our findings suggest that miR-150 binding on specific recognition sites in 3' UTR of tumor suppressor gene SRCIN1 present a potential therapeutic target for NSCLC.

Cationic liquid crystalline nanoparticles for the delivery of synthetic RNAi-based therapeutics.

RNA interference (RNAi)-based therapeutics have been used to silence the expression of targeted pathological genes. Small interfering RNA (siRNAs) and microRNA (miRNAs) inhibitor have performed this function. However, short half-life, poor cellular uptake, and nonspecific distribution of small RNAs call for the development of novel delivery systems to facilitate the use of RNAi. We developed a novel cationic liquid crystalline nanoparticle (CLCN) to efficiently deliver synthetic siRNAs and miRNAs. CLCNs were prepared by using high-speed homogenization and assembled with synthetic siRNA or miRNA molecules in nuclease-free water to create CLCN/siRNA or miRNA complexes. The homogeneous and stable CLCNs and CLCN-siRNA complexes were about 100 nm in diameter, with positively charged surfaces. CLCNs are nontoxic and are taken up by human cells though endocytosis. Significant inhibition of gene expression was detected in transiently transfected lung cancer H1299 cells treated with CLCNs/anti-GFP complexes 24 hours after transfection. Biodistribution analysis showed that the CLCNs and CLCNs-RNAi complexes were successfully delivered to various organs and into the subcutaneous human lung cancer H1299 tumor xenografts in mice 24 hours after systemic administration. These results suggest that CLCNs are a unique and advanced delivery system capable of protecting RNAi from degradation and of efficiently delivering RNAi in vitro and in vivo.

Maternal exposure to nanoparticulate titanium dioxide during the prenatal period alters gene expression related to brain development in the mouse.

BACKGROUND: Nanotechnology is developing rapidly throughout the world and the production of novel man-made nanoparticles is increasing, it is therefore of concern that nanomaterials have the potential to affect human health. The purpose of this study was to investigate the effects of maternal exposure to nano-sized anatase titanium dioxide (TiO2) on gene expression in the brain during the developmental period using cDNA microarray analysis combined with Gene Ontology (GO) and Medical Subject Headings (MeSH) terms information. RESULTS: Analysis of gene expression using GO terms indicated that expression levels of genes associated with apoptosis were altered in the brain of newborn pups, and those associated with brain development were altered in early age. The genes associated with response to oxidative stress were changed in the brains of 2 and 3 weeks old mice. Changes of the expression of genes associated with neurotransmitters and psychiatric diseases were found using MeSH terms. CONCLUSION: Maternal exposure of mice to TiO2 nanoparticles may affect the expression of genes related to the development and function of the central nervous system.

Clinically predictive factors of pathologic upstaging in patients with peripherally located clinical stage IA non-small cell lung cancer.

OBJECTIVE: Post-surgical pathologic examination often reveals a more advanced state than clinically defined in non-small cell lung cancer (NSCLC), posing the need for careful consideration of a lesser resection. We investigated the predictive factors for the pathologic upstaging in clinical stage IA NSCLC. METHODS: The clinical features of 253 consecutive patients with peripherally located T1N0M0 NSCLC who underwent complete resection between 1991 and 2004 were investigated in relation to pathologic T- and N-factors. RESULTS: Of the 253 patients, 46 (18.2%) were upstaged after surgery, due to T-factor in 12 patients, N-factor in 32, M-factor in 2 and both T- and N-factors in 1. Among the clinical parameters, a higher level of serum CEA (p=0.0378) and larger tumor size (p=0.0276) were observed in the upstaged patients. Multivariable analysis revealed that tumor size and positive serum CEA were independently associated with pathologic upstaging. When tumor size was greater than 10mm, patients with positive serum CEA (>2.0 ng/ml) showed a significantly higher incidence of pathologic upstaging (29.2%) than the rest (15.5%, p=0.0461). CONCLUSION: Clinically defined peripheral stage IA NSCLC should be carefully indicated for a lesser resection when positive serum CEA and/or tumors greater than 10mm in size are observed.

Ectopic pleural thymoma presenting as a giant mass in the thoracic cavity.

We describe a rare case of a giant thymoma that developed in the right thoracic cavity, and seemed to originate from the visceral pleura. We believe that there have been few reports of thymoma developing from such an unusual origin.

Smoking status as a prognostic factor in patients with stage I pulmonary adenocarcinoma.

BACKGROUND: Cigarette smoking is a well-known risk factor for lung carcinogenesis; however, its effect on tumor progression is still unclear. We herein investigated the influence of cigarette smoking on postoperative prognosis in patients with non-small cell lung cancer (NSCLC). METHODS: The postoperative survival and pathologic stage of 999 patients with NSCLC who underwent a curative resection were retrospectively investigated in relation to the pack-year index (PYI). RESULTS: Adenocarcinoma patients with a PYI of less than 20 showed a more favorable prognosis than those with a PYI of 20 or more, whereas no difference was observed among the subgroups of squamous cell carcinoma patients. In adenocarcinoma, stage I disease was a significantly larger population in never-smokers than in smokers. A multivariate analysis revealed that the smoking habit (yes or no) and stage (IA or IB), but not gender or histologic subtype (bronchioloalveolar type or not), are independent prognostic factors in stage I adenocarcinoma with hazard ratios of 1.8 and 2.3, respectively. CONCLUSIONS: The smoking status is a significant prognostic factor for stage I pulmonary adenocarcinoma.

[Gastrointestinal stromal tumor of the omentum: report of a case].

A 69-year old man was found a mass becoming larger in abdominal computed tomography. The mass consisted of intermingling solid and cystic component was located below the liver. Abdominal angiography showed tumor staining supplied from right gastroepiploic artery. We considered the mass cystadenoma, lymphangioma, cystic mesothelioma, or gastrointestinal stromal tumor (GIST) preoperatively, and then surgical resection was performed. The tumor was found localized in the greater omentum. Pathological examination showed the tumor composed of proliferation of atypical sort spindle cells and tumor cells were immunohistochemically positive for C-KIT and CD34, identifying the tumor as a primary GIST of the greater omentum.