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Background: The TeloVac study indicated GV1001 did not improve the survival of advanced pancreatic ductal adenocarcinoma (PDAC). However, the cytokine examinations suggested that high serum eotaxin levels may predict responses to GV1001. This Phase III trial assessed the efficacy of GV1001 with gemcitabine/capecitabine for eotaxin-high patients with untreated advanced PDAC., Methods: Patients recruited from 16 hospitals received gemcitabine (1000 mg/m 2 , D 1, 8, and 15)/capecitabine (830 mg/m 2 BID for 21 days) per month either with (GV1001 group) or without (control group) GV1001 (0.56 mg; D 1, 3, and 5, once on week 2-4, 6, then monthly thereafter) at random in a 1:1 ratio. The primary endpoint was overall survival (OS) and secondary end points included time to progression (TTP), objective response rate, and safety., Results: Total 148 patients were randomly assigned to the GV1001 (n = 75) and control groups (n = 73). The GV1001 group showed improved median OS (11.3 vs. 7.5 months, P = 0.021) and TTP (7.3 vs. 4.5 months, P = 0.021) compared to the control group. Grade >3 adverse events were reported in 77.3% and 73.1% in the GV1001 and control groups (P = 0.562), respectively., Conclusions: GV1001 plus gemcitabine/capecitabine improved OS and TTP compared to gemcitabine/capecitabine alone in eotaxin-high patients with advanced PDAC., Clinical Trial Registration: NCT02854072., (© 2023. The Author(s).)

Background A preoperative CT-based deep learning (DL) prediction model was proposed to estimate disease-free survival in patients with resected lung adenocarcinoma. However, the black-box nature of DL hinders interpretation of its results. Purpose To provide histopathologic evidence underpinning the DL survival prediction model and to demonstrate the feasibility of the model in identifying patients with histopathologic risk factors through unsupervised clustering and a series of regression analyses. Materials and Methods For this retrospective study, data from patients who underwent curative resection for lung adenocarcinoma without neoadjuvant therapy from January 2016 to September 2020 were collected from a tertiary care center. Seven histopathologic risk factors for the resected adenocarcinoma were documented: the aggressive adenocarcinoma subtype (cribriform, morular, solid, or micropapillary-predominant subtype); mediastinal nodal metastasis (pN2); presence of lymphatic, venous, and perineural invasion; visceral pleural invasion (VPI); and EGFR mutation status. Unsupervised clustering using 80 DL model-driven CT features was performed, and associations between the patient clusters and the histopathologic features were analyzed. Multivariable regression analyses were performed to investigate the added value of the DL model output to the semantic CT features (clinical T category and radiologic nodule type [ie, solid or subsolid]) for histopathologic associations. Results A total of 1667 patients (median age, 64 years [IQR, 57-71 years]; 975 women) were evaluated. Unsupervised patient clusters 3 and 4 were associated with all histopathologic risk factors ( P < .01) except for EGFR mutation status ( P = .30 for cluster 3). After multivariable adjustment, model output was associated with the aggressive adenocarcinoma subtype (odds ratio [OR], 1.03; 95% CI: 1.002, 1.05; P = .03), venous invasion (OR, 1.03; 95% CI: 1.004, 1.06; P = .02), and VPI (OR, 1.08; 95% CI: 1.06, 1.10; P < .001), independently of the semantic CT features. Conclusion The deep learning model extracted CT imaging surrogates for the histopathologic profiles of lung adenocarcinoma. © RSNA, 2022 Online supplemental material is available for this article . See also the editorial by Yanagawa in this issue.

Background: Although endoscopic resection is safe and effective for gastric epithelial neoplasms, information is limited on its efficacy and safety in extremely elderly patients who have various comorbidities. Further, the relationship between comorbidities and complications of endoscopic resection is not well established. Therefore, we aimed to evaluate the efficacy and safety of endoscopic resection of gastric epithelial neoplasms in extremely elderly patients., Methods: From October 2008 to December 2017, 4475 consecutive patients underwent endoscopic resection of gastric epithelial neoplasms. Among them, 242 were 75 years or older. We assessed Charlson comorbidity index (CCI) scores, procedural outcomes, and procedure- and sedation-related complications related to endoscopic resection., Results: Mean patient age was 78.7 ± 3.2 years. Of the 242 patients, 124 (51.2%) had low-grade dysplasia and 112 (46.3%) had adenocarcinoma. The most common comorbidity was hypertension (55.4%), followed by diabetes (23.1%). The mean CCI score was 1.67 ± 1.43. Sixty patients (24.8%) had a CCI score ≥ 3. During the procedure, 10 (4.1%) patients had desaturation that recovered by flumazenil use with mask (n = 2) or Ambu bag (n = 3) ventilation. During subsequent admission, atelectasis or pneumonia occurred in 45 (18.6%) patients, post-procedural bleeding in 12 (5.0%), and perforation in 3 (1.2%). Respiratory complications were more common in patients with a CCI score ≥ 3 (20/60, 33.3%) than in those with a CCI score < 3 (25/182, 13.7%, P = 0.002)., Conclusions: CCI score is related to respiratory complications of endoscopic resection in extremely elderly patients. Endoscopic resection must be performed cautiously, particularly in elderly patients with a high CCI score, to prevent respiratory complications.

Background: We evaluated the association between genetic variants in the Notch pathway and survival outcomes of patients with surgically resected NSCLC., Methods: Sixty-four single nucleotide polymorphisms (SNPs) in the Notch pathway genes were evaluated in the discovery study (n = 354) and two sequential validation studies (n = 772 and n = 746, respectively). The association of genotype with overall survival (OS) and disease-free survival (DFS) was evaluated., Results: Of the 64 SNPs analyzed in the discovery study, 9 were significantly associated with OS or DFS. Among them, the association remained significant only for Deltex-1 (DTX1) rs1732786A>G in the first validation study. The second validation study confirmed again the association between DTX1 rs1732786A>G and survival outcomes. In the combined analysis, rs1732786A>G was significantly associated with better OS and DFS (adjusted HR ·aHR· for OS, 0.75; 95% CI 0.64-0.87; P = 0.0002; aHR for DFS, 0.79; 95% CI 0.71-0.89; P = 0.0001). In vitro luciferase assay showed that the rs1732786G allele was associated with higher promoter activity compared to rs1732786A allele. Consistently, relative mRNA expression level of DTX1 showed significant positive correlation with rs1732786 A-to-G change (P trend  = 0.02) in tumor tissues., Conclusions: These results suggest that DTX1 rs1732786 is a potential prognostic factor that may have clinical utility in the management of early stage NSCLC.

Purpose: To evaluate the value of a vessel removal algorithm in segmentation of subsolid nodules by comparing the software solid component measurement on CT, before and after vessel removal, with the measurement of the invasive component on pathology in lung adenocarcinomas manifesting as subsolid nodules., Materials and Methods: Between January 2014 and June 2015, 73 subsolid nodules with an invasive component of ≤10 mm on pathology were selected for analyses. For each nodule, semi-automated segmentation was performed by 2 radiologists and 3-dimensional (D) longest, axial longest and effective diameters of solid component were obtained from software, before and after using a vessel removal tool. These measurements were compared with the invasive component diameter on pathology using the paired t-test and Pearson's correlation test., Results: Sixty-eight successfully segmented subsolid nodules were included. The mean maximal diameter of the invasive component on pathology was 4.6 mm (range, 0-10 mm). The correlation between software and pathology measurements was significant (p < 0.01) and the correlation after vessel removal (r = 0.49-0.54) was better than before vessel removal (r = 0.27-0.41). The mean measurement difference between solid component on CT and invasive tumor on pathology was significantly larger before vessel removal than after vessel removal in all measurements. The smallest mean measurement difference was obtained with 3D longest diameter of solid component after vessel removal in both readers (-0.26 mm to 0.10 mm), with no significant difference from pathology (p = 0.53-0.83)., Conclusion: By adding a vessel removal algorithm in software segmentation of subsolid nodules, the prediction of invasive component in lung adenocarcinomas can be improved., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objectives: To retrospectively evaluate the feasibility of CT assessment-based direct surgical resection of part-solid nodules (PSNs) with solid components > 5 mm without preoperative percutaneous transthoracic needle biopsies (PTNBs)., Methods: From January 2009-December 2014, 85 PSNs with solid components > 5 mm on CT were included. Preoperative PTNBs were performed for 41 PSNs (biopsy group) and CT assessment-based direct resections were performed for 44 PSNs (direct surgery group). Diagnostic accuracy and complication rates of the groups were compared., Results: Pathological results of 83 PSNs excluding two indeterminate nodules included 76 adenocarcinomas (91.6%), two adenocarcinomas in situ (2.4%) and five benign lesions (6.0%). In the biopsy group, the overall sensitivity, specificity and accuracy for the diagnosis of adenocarcinoma were 78.9% (30/38), 100% (1/1) and 79.5% (31/39), respectively. Pneumothorax and haemoptysis occurred in 11 procedures (26.8%). In the direct surgery group, the respective values for the diagnosis of adenocarcinoma were 100% (38/38), 0% (0/6) and 86.4% (38/44), respectively. Seven pneumothoraces (15.9%); no haemoptysis occurred during localization procedures. There were no significant differences in diagnostic accuracy (P = 0.559) between the two groups., Conclusions: CT assessment-based direct resection can be reasonable for PSNs with solid part > 5 mm., Key Points: • 91.6% of PSNs with solid component > 5 mm were adenocarcinomas. • PTNBs for PSNs with solid component > 5 mm had 79.5% accuracy. • CT-based resection for PSNs with solid component > 5 mm had 86.4% accuracy. • CT-based resection without biopsy can be a reasonable option in routine practice.

Purpose: To determine if the radiomic features on CT can predict progression-free survival (PFS) in epidermal growth factor receptor (EGFR) mutant adenocarcinoma patients treated with first-line EGFR tyrosine kinase inhibitors (TKIs) and to identify the incremental value of radiomic features over conventional clinical factors in PFS prediction., Methods: In this institutional review board-approved retrospective study, pretreatment contrast-enhanced CT and first follow-up CT after initiation of TKIs were analyzed in 48 patients (M:F = 23:25; median age: 61 years). Radiomic features at baseline, at 1st first follow-up, and the percentage change between the two were determined. A Cox regression model was used to predict PFS with nonredundant radiomic features and clinical factors, respectively. The incremental value of radiomic features over the clinical factors in PFS prediction was also assessed by way of a concordance index., Results: Roundness (HR: 3.91; 95% CI: 1.72, 8.90; P = 0.001) and grey-level nonuniformity (HR: 3.60; 95% CI: 1.80, 7.18; P<0.001) were independent predictors of PFS. For clinical factors, patient age (HR: 2.11; 95% CI: 1.01, 4.39; P = 0.046), baseline tumor diameter (HR: 1.03; 95% CI: 1.01, 1.05; P = 0.002), and treatment response (HR: 0.46; 95% CI: 0.24, 0.87; P = 0.017) were independent predictors. The addition of radiomic features to clinical factors significantly improved predictive performance (concordance index; combined model = 0.77, clinical-only model = 0.69, P<0.001)., Conclusions: Radiomic features enable PFS estimation in EGFR mutant adenocarcinoma patients treated with first-line EGFR TKIs. Radiomic features combined with clinical factors provide significant improvement in prognostic performance compared with using only clinical factors.

Objective: The objective of our study was to determine whether visceral pleural invasion (VPI) of T1-sized peripheral pulmonary adenocarcinomas manifesting as subsolid nodules (SSNs) abutting the pleural surface or associated with pleural tags can be predicted., Materials and Methods: Our study population consisted of 188 T1-sized peripheral pulmonary adenocarcinomas that appeared as SSNs (24 pure ground-glass nodules [GGNs] and 164 part-solid nodules) and underwent surgical resection between January 2007 and December 2013. Logistic regression analysis was performed to identify significant factors in predicting VPI., Results: VPI occurred in 36 of 188 adenocarcinomas (19.1%). There were no cases of VPI in patients with pure GGNs. In part-solid nodules, there were significant differences regarding the presence of pleural contact, presence of pleural thickening, presence of solid portion abutting the pleura, nodule size, solid portion size, solid proportion, interface length, and length of the solid portion contacting the pleura (p < 0.05). Multivariate analysis revealed pleural contact (p < 0.001), pleural thickening (p = 0.003), solid proportion greater than 50% (p = 0.002), and nodule size greater than 20 mm (p = 0.015) as significant independent predictive features for VPI with adjusted odds ratios of 8.300, 3.966, 4.636, and 2.993, respectively., Conclusion: In part-solid nodules, the CT features of pleural contact, pleural thickening, solid proportion greater than 50%, and nodule size greater than 20 mm were shown to be significant indicators of VPI by T1-sized peripheral adenocarcinomas.

Objectives: To compare interobserver agreements among multiple readers and accuracy for the assessment of solid components in subsolid nodules between the lung and mediastinal window settings., Methods: Seventy-seven surgically resected nodules with solid components smaller than 8 mm were included in this study. In both lung and mediastinal windows, five readers independently assessed the presence and size of solid component. Bootstrapping was used to compare the interobserver agreement between the two window settings. Imaging-pathology correlation was performed to evaluate the accuracy., Results: There were no significant differences in the interobserver agreements between the two windows for both identification (lung windows, k = 0.51; mediastinal windows, k = 0.57) and measurements (lung windows, ICC = 0.70; mediastinal windows, ICC = 0.69) of solid components. The incidence of false negative results for the presence of invasive components and the median absolute difference between the solid component size and the invasive component size were significantly higher on mediastinal windows than on lung windows (P < 0.001 and P < 0.001, respectively)., Conclusions: The lung window setting had a comparable reproducibility but a higher accuracy than the mediastinal window setting for nodule classifications and solid component measurements in subsolid nodules., Key Points: • Reproducibility was similar between the two windows in nodule classifications. • Reproducibility was similar between the two windows in solid component measurements. • Accuracy for solid component assessment was higher on lung windows.

Objective: To investigate whether "follow-up and surgical resection after interval growth" can negatively influence recurrence or mortality in patients with persistent part-solid nodules (PSNs) with solid components ≤5 mm., Methods: One hundred twenty five surgically resected persistent PSNs with solid components ≤5 mm in 125 individuals were evaluated. Of the 125 PSNs, 54 and 71 PSNs were categorized into interval growth and immediate surgery groups, respectively. Cox regression analysis was performed to evaluate the association of "follow-up until interval growth" with recurrence and survival, adjusted for initial clinical and CT features., Results: In the interval growth group, 30 patients showed increased nodule size, 10 increased solid parts, and the remaining 14 both patterns. Five patients showed clinical stage shifts (stage T1a, initially, to T1b after interval growth). Post-operative disease recurrence occurred in six individuals (interval growth group, n = 2/54; immediate surgery group, n = 4/71), and four individuals died (interval growth group, n = 1/54; immediate surgery group, n = 3/71). There were no significant differences between these two groups in terms of recurrence-free survival (p = 0.451) and overall survival (p = 0.185)., Conclusion: "Follow-up and surgical resection after interval growth" did not negatively influence the prognosis of patients with persistent PSNs with solid components ≤5 mm., Key Points: • Incidences of post-operative recurrence or death in patients with PSN are low. • "Follow-up until interval growth" of PSNs does not negatively influence disease recurrence. • There was no survival disadvantage related with "follow-up until interval growth" in PSNs.

Objective: To evaluate the performance of software in segmenting ground-glass and solid components of subsolid nodules in pulmonary adenocarcinomas., Method: Seventy-three pulmonary adenocarcinomas manifesting as subsolid nodules were included. Two radiologists measured the maximal axial diameter of the ground-glass components on lung windows and that of the solid components on lung and mediastinal windows. Nodules were segmented using software by applying five (-850 HU to -650 HU) and nine (-130 HU to -500 HU) attenuation thresholds. We compared the manual and software measurements of ground-glass and solid components with pathology measurements of tumour and invasive components., Results: Segmentation of ground-glass components at a threshold of -750 HU yielded mean differences of +0.06 mm (p = 0.83, 95 % limits of agreement, 4.51 to 4.67) and -2.32 mm (p < 0.001, -8.27 to 3.63) when compared with pathology and manual measurements, respectively. For solid components, mean differences between the software (at -350 HU) and pathology measurements and between the manual (lung and mediastinal windows) and pathology measurements were -0.12 mm (p = 0.74, -5.73 to 5.55]), 0.15 mm (p = 0.73, -6.92 to 7.22), and -1.14 mm (p < 0.001, -7.93 to 5.64), respectively., Conclusion: Software segmentation of ground-glass and solid components in subsolid nodules showed no significant difference with pathology., Key Points: • Software can effectively segment ground-glass and solid components in subsolid nodules. • Software measurements show no significant difference with pathology measurements. • Manual measurements are more accurate on lung windows than on mediastinal windows.

Objectives: To evaluate the differences in semi-automatic measurements of CT attenuation and volume of part-solid nodules (PSNs) between unenhanced and enhanced CT scans., Materials and Methods: CT scans including unenhanced and enhanced phases (slice thickness 0.625 and 1.25mm, respectively) for 53 adenocarcinomas presenting as PSNs in 50 patients were retrospectively evaluated. For each nodule, semi-automatic segmentation provided the diameter, mean attenuation, mass, and volume of a whole nodule and its solid component. Interscan variability and statistical significance of the differences in those measures according to the adenocarcinoma category were evaluated by one reader., Results: All parameters except for the mean attenuation of the solid components, were significantly increased on enhanced CT (p<0.05). For the whole nodule, the mean relative differences were as follows: the longest diameter, 1.4% (limits of agreement, -6.2-9.1); volume, 2.4% (-26.7-31.4); mass, 7.0% (-11.3-25.2); mean attenuation, 2.7% (-5.6-11). For the nodule's solid component, those differences were as follow: the longest diameter, 6.9% (-34.4-48.2); volume, 17.9% (-77.8-113.7); mass, 18.8% (-77.8-115.4). The differences of measures between the unenhanced and enhanced CT were not significantly different between two groups of adenocarcinoma in situ/minimally invasive adenocarcinomas and invasive adenocarcinomas (p>0.05)., Conclusions: As most volumetric and attenuation measurements changed significantly after contrast enhancement, care should be taken in comparing unenhanced and enhanced CT in the evaluation of PSNs., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objective: To investigate the natural course of persistent pulmonary subsolid nodules (SSNs) with solid portions ≤5 mm and the clinico-radiological features that influence interval growth over follow-ups., Methods: From 2005 to 2013, the natural courses of 213 persistent SSNs in 213 patients were evaluated. To identify significant predictors of interval growth, Kaplan-Meier analysis and Cox proportional hazard regression analysis were performed., Results: Among the 213 nodules, 136 were pure ground-glass nodules (GGNs; growth, 18; stable, 118) and 77 were part-solid GGNs with solid portions ≤5 mm (growth, 24; stable, 53). For all SSNs, lung cancer history (p = 0.001), part-solid GGNs (p < 0.001), and nodule diameter (p < 0.001) were significant predictors for interval growth. On subgroup analysis, nodule diameter was an independent predictor for the interval growth of both pure GGNs (p < 0.001), and part-solid GGNs (p = 0.037). For part-solid GGNs, lung cancer history (p = 0.002) was another significant predictor of the interval growth. Interval growth of pure GGNs ≥10 mm and part-solid GGNs ≥8 mm were significantly more frequent than in pure GGNs <10 mm (p < 0.001) and part-solid GGNs <8 mm (p = 0.003), respectively., Conclusion: The natural course of SSNs with solid portions ≤5 mm differed significantly according to their nodule type and nodule diameters, with which their management can be subdivided., Key Points: • Pure GGNs ≥10 mm have significantly more frequent interval growth than those <10 mm. • Part-solid GGNs ≥8 mm have significantly more frequent interval growth than those <8 mm. • Management of SSNs with solid portions ≤5 mm can be subdivided by diameter.

Mesonephric adenocarcinoma is a rare tumor type that is usually found in areas where the Wolffian duct was present during the fetal period. We report a case of mesonephric adenocarcinoma of the uterine corpus in a 66-year-old woman who presented with vaginal bleeding. Pelvic magnetic resonance imaging revealed a 2.7-cm-sized irregular thickening and enhancement of the uterine body. The diagnosis following endometrial curettage biopsy was endometrioid adenocarcinoma, and the patient underwent a total hysterectomy with bilateral salpingo-oophorectomy. The tumor was composed of small tubular and ductal components, and a retiform appearance was also observed in the deeper areas. The tumor cells were immunopositive for cytokeratin, vimentin, CD10 with a luminal staining pattern, PAX2, and PAX8, and immunonegative for estrogen receptor and progesterone receptor, which was consistent with tumor of mesonephric origin. Mesonephric neoplasms reveal relatively low-grade nuclear feature, characteristic immunoprofiles (immunonegative for ER and PR, and immunopositive for CD10, PAX2, PAX8, and GATA3), and unique tumor location (myometrium), whereas Müllerian neoplasms such as endometrial adenocarcinoma show various morphology, immunopositivity for ER and PR, and primarily endometrial location. As described above, an integration of the clinical features, morphologic characteristics, and immunohistochemical profiles is needed to make a diagnosis., (© The Author(s) 2015.)

The purpose of the present study was to compare the frequency of microscopic invasions, disease-free-survival (DFS), and the frequency and pattern of disease recurrence between stage I pulmonary adenocarcinomas appearing as solid nodules and those appearing as part-solid ground-glass nodules (GGNs) after matching their solid parts' size (D(solid)) and patients' age. Among 501 patients who underwent curative surgery for stage I pulmonary adenocarcinomas between 2003 and 2011, 172 patients (86 with solid nodules [M: F = 36: 50; mean age, 62.8 years] and 86 with part-solid GGNs [M:F = 30:56; mean age, 63.0 years]) matched for D(solid) and patients' age were included. DFS, frequency of microscopic invasions, recurrence, and recurrence pattern were compared between the two groups. No significant difference was observed in the frequency of microscopic invasions between the two groups (visceral pleural invasion, 30.23% vs. 29.07%, P = 0.867; lymphatic invasion, 5.81% vs. 3.49%, P = 0.720; vascular invasion, 1.16% vs. 0%, P = 1.000; solid nodules vs. part-slid GGNs, respectively) and DFS (estimated 5-year DFS, 83.6% vs. 81.9%, P = 0.744; solid nodules vs. part-slid GGNs, respectively). As for recurrence and recurrence pattern, there were no significant differences between the solid nodule group (14/86), and part-solid GGN group (12/86) (P = 0.670). Lung parenchymal nodules were the most frequent pattern of disease recurrence in both groups, followed by pleural seeding. In conclusion, after matching D(solid) and patients' age, there was no significant difference in the frequency of microscopic invasions, DFS, and the frequency and pattern of recurrence between stage I pulmonary adenocarcinomas appearing as solid nodules and part-solid GGNs.

Objective: To evaluate the differentiating potentials of computed tomography texture analysis for invasive pulmonary adenocarcinomas (IPAs) from their preinvasive lesions or minimally invasive adenocarcinomas (MIAs) manifesting as persistent pure ground-glass nodules (PGGNs) larger than 5 mm., Materials and Methods: This institutional review board-approved retrospective study included 63 patients (23 men and 40 women) with 66 PGGNs larger than 5 mm on unenhanced computed tomography from 2005 to 2013. All PGGNs were pathologically confirmed and categorized into 2 groups [IPAs (n = 11) vs preinvasive lesions (n = 41)/MIAs (n = 14)]. Each PGGN was segmented manually, and their texture features were quantitatively extracted. To identify significant differentiating factors of IPAs from preinvasive lesions/MIAs, multivariate logistic regression and C-statistic analyses were performed., Results: Between IPAs and preinvasive lesions/MIAs, nodule size, volume, mass, entropy, effective diameter, and surface area were significantly different (P < 0.05), and homogeneity and gray level co-occurrence matrix inverse difference moment showed marginal significance (P < 0.10). Subsequent multivariate analysis revealed larger nodule mass [adjusted odds ratio (OR), 11.92], higher entropy (adjusted OR, 35.12), and lower homogeneity (adjusted OR, 0.278 × 10) as independent differentiating factors of IPAs. Subgroup analysis showed that larger nodule mass, higher entropy, and lower homogeneity were also significant differentiating variables of IPAs in nodules of diameter 10 mm or larger. A multiple logistic regression model using these features showed excellent [area under the curve (AUC), 0.962] and significantly higher differentiating performance compared to nodule size (AUC, 0.712) or mass (AUC, 0.788) alone., Conclusion: Computed tomography texture features such as higher entropy and lower homogeneity were significant differentiating factors of IPAs presenting as PGGNs larger than 5 mm and have potentials to enhance the differentiating performance.

Objectives: We aimed to retrospectively investigate CT findings of minimally invasive adenocarcinoma (MIA) and to determine the appropriate method for measurement of solid portions in MIAs at CT., Methods: From May 2012 to April 2014, 55 pulmonary nodules in 52 patients were pathologically confirmed as MIAs and were included in this study. CT findings of MIAs and measurements of solid portions at CT were evaluated by two independent radiologists., Results: Mean size of MIAs was 10.5 mm ± 4.8 (range, 4-28 mm). Fifty-two MIAs manifested as 28 pure ground glass nodules (GGNs) (53.8 % %), 22 part-solid GGNs (42.3 % %), and 2 two solid nodules (3.8 % %) at CT. Lobulated border, bubble lucency, and pleural retraction were frequently found in both observers (26.9-42.3 % %). Differences according to window settings between solid portion size and invasive component size were not significantly different in both observers (p > 0.05). As for interobserver agreement, 95 % CIs for solid portion size in the mediastinal window setting (-2.2 to 3.4; mean, 0.6) were slightly narrower than those in the lung window setting (-2.6 to 3.1; mean, 0.3)., Conclusions: Nearly all MIAs appear as pure and part-solid GGNs. Mediastinal and lung window settings can be applied for measurement of solid portions at CT without a significant difference., Key Points: • Nearly all MIAs appear as pure and part-solid GGNs. • MIAs show frequent interval growth at follow-up. • MIAs with solid portion ≥5 mm ranged from 7.7 % to 19.2 %. • Mediastinal and lung window settings can be applied for solid portion measurement.

Background: Endoscopic submucosal dissection (ESD) has been widely performed for the treatment of early gastric cancer (EGC). The aim of this study is to examine the effectiveness of ESD in submucosal invasive gastric cancers (SM-GC), with a special focus on patients who underwent non-curative resection., Methods: Data for 1,246 patients who underwent ESD for treatment of EGC at six medical centers in Daegu-Gyeongbuk, Korea, between February 2003 and May 2010 were collected. After retrospective analysis of ESD databases, 118 patients were enrolled and classified into three groups: (1) EGC with submucosal invasion less than 500 μm (SM1-GC) that met the expanded criteria (EC) (SM1 EC, n = 42); (2) SM1-GC that did not meet the EC (SM1 non-EC, n = 38); and (3) EGC with submucosal invasion greater than 500 μm (SM2-GC, n = 38)., Results: The en bloc and complete resection rates did not differ significantly among the three groups. However, the curative resection rate was significantly better in the SM1 EC group (69.0%) compared to that in SM1 non-EC and SM2-GC groups (0% in both cases). Out of a total of 118 patients, 89 (75.4%) underwent non-curative resection, and cancer recurrence was observed in 9 (9/89, 10.1%). We analyzed the survival rate in these non-curative patients and the overall survival and disease-free survival did not differ significantly between patients that were treated with additional surgical resection and those that were simply followed up after ESD., Conclusions: Non-curative resection in SM-GC does not always lead to cancer recurrence. Thus, if additional surgery cannot be performed because of the patient's unsuitable condition or refusal, a close follow-up with endoscopy can be considered as an alternative for carefully selected patients. Moreover, as the ESD technology continues to evolve, it might be possible to expand the criteria for curative ESD in patients with SM-GC.

Objective: To assess whether measuring the solid portion of adenocarcinomas appearing as part-solid ground-glass nodules (GGNs) can predict a patient's prognosis accurately and how the prognosis corresponds to that of solid nodules., Methods: 501 patients (solid nodule group, 304; part-solid GGN group, 197) underwent curative surgery for stage I adenocarcinomas. Maximal diameters of the whole lesion including ground-glass opacities (D whole ) and solid components only (D solid ) were measured on CT. Disease-free survival (DFS) and overall survival (OS) were calculated from the date of surgery., Results: D solid was a significant prognostic factor in the part-solid GGN group, while D whole was not. Part-solid GGNs with D solid ≤2 cm showed significantly better DFS (P = 0.016) and OS (P = 0.004) than solid nodules; however, those with D solid >2 cm did not show a significant difference. Hazard ratio (HR) for increase in D solid was significantly greater in part-solid GGNs than in solid nodules (P = 0.009). For OS, HR for increase in D solid was greater in part-solid GGNs than in solid nodule, which was marginally not significant (P = 0.060)., Conclusion: D solid was better than D whole for prognosis prediction of adenocarcinomas appearing as part-solid GGNs. In addition, the influence of D solid on prognosis in the part-solid GGN group was greater than in the solid nodule group., Key Points: • Dsolid is a better prognosis indicator than Dsolid in part-solid GGN adenocarcinomas • Part-solid GGN adenocarcinoma show better prognosis than solid adenocarcinomas when Dsolid ≤2 cm • Dsolid has greater prognostic influence in part-solid GGN adenocarcinomas than solid adenocarcinomas.

Purpose: To retrospectively investigate the value of computerized three-dimensional texture analysis for differentiation of preinvasive lesions from invasive pulmonary adenocarcinomas (IPAs) that manifest as part-solid ground-glass nodules (GGNs)., Materials and Methods: The institutional review board approved this retrospective study with a waiver of patients' informed consent. The study consisted of 86 patients with 86 pathologic analysis-confirmed part-solid GGNs (mean size, 16 mm ± 5.4 [standard deviation]) who had undergone computed tomographic (CT) imaging between January 2005 and October 2011. Each part-solid GGN was manually segmented and its computerized texture features were quantitatively extracted by using an in-house software program. Multivariate logistic regression analysis was performed to investigate the differentiating factors of preinvasive lesions from IPAs. Three-layered artificial neural networks (ANNs) with a back-propagation algorithm and receiver operating characteristic curve analysis were used to build a discriminating model with texture features and to evaluate its discriminating performance., Results: Pathologic analysis confirmed 58 IPAs (seven minimally invasive adenocarcinomas and 51 invasive adenocarcinomas) and 28 preinvasive lesions (four atypical adenomatous hyperplasias and 24 adenocarcinomas in situ). IPAs and preinvasive lesions exhibited significant differences in various histograms and volumetric parameters (P < .05). Multivariate analysis revealed that smaller mass (adjusted odds ratio, 0.092) and higher kurtosis (adjusted odds ratio, 3.319) are significant differentiators of preinvasive lesions from IPAs (P < .05). With mean attenuation, standard deviation of attenuation, mass, kurtosis, and entropy, the ANNs model showed excellent accuracy in differentiation of preinvasive lesions from IPAs (area under the curve, 0.981)., Conclusion: In part-solid GGNs, higher kurtosis and smaller mass are significant differentiators of preinvasive lesions from IPAs, and preinvasive lesions can be accurately differentiated from IPAs by using computerized texture analysis. Online supplemental material is available for this article., (© RSNA, 2014.)

Background: Early discrimination between transient and persistent par-solid ground-glass nodules (PSNs) at CT is essential for patient management. The objective of our study was to retrospectively investigate the value of texture analysis in differentiating pulmonary transient and persistent PSNs in addition to clinical and CT features., Methods: This retrospective study was performed with IRB approval and a waiver of the requirement for patients' informed consent. From January 2007 to October 2009, we identified 77 individuals (39 men and 38 women; mean age, 55 years) with 86 PSNs on thin-section chest CT. Thirty-nine PSNs in 31 individuals were transient and 47 PSNs in 46 patients were persistent. The clinical, CT, and texture features of PSNs were evaluated. To investigate the additional value of texture analysis in differentiating transient from persistent PSNs, logistic regression analysis and C-statistics were performed., Results: Between transient and persistent PSNs, there were significant differences in age, gender, smoking history, and eosinophil count among the clinical features. As for thin-section CT features, there were significant differences in lesion size, solid portion size, and lesion multiplicity. In terms of texture features, there were significant differences in mean attenuation, skewness of whole PSN, attenuation ratio of whole PSN to inner solid portion, and 5-, 10-, 25-, 50-percentile CT numbers of whole PSN. Multivariate analysis revealed eosinophilia, lesion size, lesion multiplicity, mean attenuation of whole PSN, skewness of whole PSN, and 5-percentile CT number were significant independent predictors of transient PSNs. (P<0.05) C-statistics revealed that texture analysis incorporating clinical and CT features (AUC, 92.9%) showed significantly higher differentiating performance of transient from persistent PSNs compared with the clinical and CT features alone (AUC, 79.0%). (P =  0.004)., Conclusion: Texture analysis of PSNs in addition to clinical and CT features analysis has the potential to improve the differentiation of transient from persistent PSNs.

Introduction: We aimed to evaluate the correlation between the size of the solid component on thin-section computed tomography (CT) and invasive component on pathology in small lung adenocarcinomas manifesting as subsolid nodules., Methods: Fifty-nine subsolid nodules in 58 patients were evaluated. The maximum diameters of subsolid nodules and the solid component on CT were measured by two radiologists in three-dimensional (3D) and two-dimensional (2D) planes using in-house software. In addition, the maximum diameters of the tumor and invasive component were measured on pathology by two pathologists. CT measurements were compared with pathologic measurements., Results: There was a strong correlation between the size of the solid component on CT and invasive component on pathology, as well as the size of subsolid nodules and the tumor size (r = 0.82-0.87 for 3D measurement, 0.72-0.88 for 2D measurement; p < 0.0001). The size of subsolid nodules in 3D and 2D measurements was significantly larger than tumor size (p < 0.0001). In regard to measurement of the solid component, 3D measurements tended to be larger than the size of the invasive component whereas 2D measurement tended to be similar to the size of the invasive component. By applying a size criteria of solid component that was 3 mm or lesser in maximum diameter, preinvasive and minimally invasive adenocarcinoma was predicted with a specificity of 100% (28 of 28)., Conclusion: We found a significant correlation between the size of the solid component on thin-section CT and the invasive component on pathology.

Purpose: To retrospectively investigate the differentiating computed tomographic (CT) features between invasive pulmonary adenocarcinoma (IPA) and preinvasive lesions appearing as ground-glass nodules (GGNs) in 253 patients., Materials and Methods: This study was approved by the institutional review board. From January 2005 to October 2011, 272 GGNs were pathologically confirmed (179 IPAs and 93 preinvasive lesions) in 253 patients and were included in this study. There were 64 pure GGNs and 208 part-solid GGNs. Preinvasive lesions consisted of 21 atypical adenomatous hyperplasias and 72 adenocarcinomas in situ. To identify the differentiating CT features between IPAs and preinvasive lesions and to evaluate their differentiating accuracy, logistic regression analysis and receiver operating characteristic (ROC) curve analysis were performed, respectively., Results: In pure GGNs, preinvasive lesions were significantly smaller and more frequently nonlobulated than IPAs (P < .05). Multivariate analysis revealed that lesion size was the single significant differentiator of preinvasive lesions from IPAs (P = .029). The optimal cut-off size for preinvasive lesions was less than 10 mm (sensitivity, 53.33%; specificity, 100%). In part-solid GGNs, there were significant differences in lesion size, solid portion size, solid proportion, margin, border, and pleural retraction between IPAs and preinvasive lesions (P < .05). Multivariate analysis revealed that smaller lesion size, smaller solid proportion, nonlobulated border, and nonspiculated margin were significant differentiators of preinvasive lesions (P < .05), with excellent differentiating accuracy (area under ROC curve, 0.905)., Conclusion: In pure GGNs, a lesion size of less than 10 mm can be a very specific discriminator of preinvasive lesions from IPAs. In part-solid GGNs, preinvasive lesions can be accurately distinguished from IPAs by the smaller lesion size, smaller solid proportion, nonlobulated border, and nonspiculated margin.

Introduction: ALK rearrangement in lung cancer has been identified as a novel molecular target in lung adenocarcinoma. In this study, we evaluated metabolic and metastatic features of lung adenocarcinoma by using FDG PET/CT, with regard to specific genotypes of ALK and EGFR mutation., Methods: Patients with lung adenocarcinoma initially diagnosed and examined with FDG PET/CT and molecular genotyping with biopsy specimen, from September 2009 to September 2011, were selected retrospectively. ALK fluorescence in situ hybridization and EGFR mutations were tested. Maximum standardized uptake value (SUVmax) and metastatic characteristics on FDG PET/CT were analyzed with regard to ALK and EGFR status., Results: Of the 331 lung adenocarcinoma patients, 18 were ALK positive (ALK(+)), 156 were EGFR mutation positive (EGFR(+)), and 157 were wild type (WT) for both ALK and EGFR mutation. The ALK(+) tumor showed significantly higher SUVmax and more common metastasis to lymph nodes and distant organs than those of other genotypes in overall patients (P<0.01). In a subgroup analysis of advanced stage (stage IIIb and IV), ALK(+) lung cancer showed significantly higher SUVmax (P<0.05) than EGFR(+) tumors. In another subgroup analysis of size matched groups, ALK(+) tumors showed significant difference in SUVmax, lymph node and distant metastasis (P<0.01), particularly in the moderate-sized tumors (1.5-3cm)., Conclusion: ALK-rearranged lung adenocarcinoma represents higher glucose metabolism and more rapid metastasis to lymph nodes or distant sites compared with those with EGFR mutation and wild type, which suggests more aggressive features of ALK rearrangement., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

In 2011, the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society proposed a new classification for lung adenocarcinoma that included a number of changes to previous classifications. This classification now considers resection specimens, small biopsies, and cytology specimens. Two former histopathologic terms, bronchioloalveolar carcinoma and mixed subtype adenocarcinoma, are no longer to be used. For resection specimens, the new terms of adenocarcinoma in situ and minimally invasive adenocarcinoma are introduced for small adenocarcinomas showing pure lepidic growth and predominantly lepidic growth, with invasion ≤5 mm, respectively. Invasive adenocarcinomas are now classified by their predominant pattern as lepidic, acinar, papillary, and solid; a micropapillary pattern is newly added. This classification also provides guidance for small biopsies and cytology specimens. For adenocarcinomas that include both an invasive and a lepidic component, it is suggested that for T staging the size of the T-factor may be best measured on the basis of the size of the invasive component rather than on the total size of tumors including lepidic components, both on pathologic and computed tomography assessment. This suggestion awaits confirmation in clinical-radiologic trials. An implication for M staging is that comprehensive histologic subtyping along with other histologic and molecular features can be very helpful in determining whether multiple pulmonary nodules are separate primaries or intrapulmonary metastases. In this review article, we provide an illustrated overview of the proposed new classification for lung adenocarcinoma with an emphasis upon what the radiologist needs to know in order to successfully contribute to the multidisciplinary strategic management of patients with this common histologic subtype of lung cancer.

The International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society recently introduced a new classification of lung adenocarcinoma addressing the latest advances in oncology, molecular biology, pathology, radiology, and surgery of lung adenocarcinoma. In this classification, new uniform terminology and diagnostic criteria are described, including the introduction of adenocarcinoma in situ as a second preinvasive lesion, as well as the concept of minimally-invasive adenocarcinoma and new subtyping of invasive adenocarcinomas stratified according to predominant patterns. In addition, the previously widely-used term bronchioloalveolar carcinoma is no longer considered valid and has been recategorized. This classification also provides, for the first time, guidance for small biopsies and cytology specimens. This new classification has profound implications for radiology, as much investigation will be needed to correlate these newly introduced concepts (such as histologic subtypes) with radiologic features. Understanding the newly described concept of minimally-invasive adenocarcinoma will be essential in determining sublobar resection for adenocarcinomas. In this manuscript, we briefly review the new classification of lung adenocarcinoma and discuss its radiologic relevance to the reporting, biopsy, and future studies of adenocarcinoma.

Synchronous carcinomas of the esophagus and other organs are relatively uncommon. A 65-year old man with synchronous carcinomas of the esophagus and stomach underwent esophageal reconstruction using a gastric tube following endoscopic submucosal dissection.

Background: Little is known about the feasibility of endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR) for patients with chronic renal failure (CRF) or liver cirrhosis (LC). This study aimed to assess the safety, efficacy, and clinical outcomes of EMR or ESD in patients with CRF or LC compared to those in patients without., Methods: Between February 2003 and November 2009, a total of 1016 gastric neoplastic lesions in 928 patients were treated by using EMR or ESD. Among them, 18 patients had LC and 17 patients had CRF. Their medical records were reviewed retrospectively. En bloc resection rate, histological complete resection rate, operation time, and complications were compared between patients with CRF or LC and those without (control group)., Results: Baseline characteristics were not significantly different between the CRF, LC, and control groups except for a high rate of comorbidities in the CRF group and prolonged prothrombin time in the LC group. Operation time and therapeutic outcomes such as en bloc and complete resection rates did not differ significantly between the groups. Immediate bleeding tended to occur more frequently in the CRF+LC group than in controls (47.5 vs. 33.9%, p=0.077). There was no significant difference in the incidence of perforation between the CRF, LC, and control groups. The hospital stay was longer in the CRF+LC group than in the control group (6.4±3.53 vs. 4.9±3.15 days, p=0.012)., Conclusions: EMR and ESD for the treatment of early gastric neoplasia may be equally effective and tolerable in the CRF or the LC group compared to the control group, although patients with CRF or LC might need the longer admission period than the control group.

Objective: The purpose of this article is to review the clinical significance of ground-glass nodules (GGNs) in the management of lung adenocarcinoma., Conclusion: GGNs can serve as imaging biomarkers that represent the bronchioloalveolar carcinoma component in adenocarcinoma on histology and indicate a better prognosis in patients with lung adenocarcinoma. The evolution of GGNs reflects the multistep progression of adenocarcinoma. Despite the high probability of malignancy of GGNs, the possibility of overdiagnosis should be considered in the management of GGNs.

Objective: It was our aim to evaluate the usefulness of napsin A and thyroid transcription factor 1 (TTF-1) in the differential diagnosis of metastatic pulmonary and non-pulmonary adenocarcinomas (ACs) in pleural effusion., Study Design: A total of 84 pleural effusion fluid cell blocks were collected from metastatic ACs. There were 53 pulmonary ACs and 31 non-pulmonary ACs. Immunohistochemical staining was performed with antibodies against napsin A and TTF-1., Results: Napsin A was positive in 44/53 (83%) cases of pulmonary ACs, and TTF-1 was positive in 30/53 (57%) cases of pulmonary ACs. All non-pulmonary ACs were negative for napsin A and TTF-1. Napsin A showed a reactivity in >75% of the tumor cells in 36 of the 44 positive cases (82%), whereas TTF-1 showed a reactivity in >75% of the tumor cells only in 6 of the 30 positive cases (20%; p < 0.01). Poorly differentiated pulmonary ACs expressed napsin A (73%) more frequently than TTF-1 (53%), but this was not statistically significant (p = 0.45)., Conclusion: We conclude that napsin A is superior to TTF-1 with regard to distinguishing between metastatic pulmonary and non-pulmonary ACs in cell blocks prepared from malignant pleural effusions., (Copyright © 2011 S. Karger AG, Basel.)

It has been suggested that a high EGFR gene copy number may be an indicator of good response to EGFR tyrosine kinase inhibitor therapy and a marker of poor prognosis in NSCLC. However, imaging features related to EGFR gene copy number status in adenocarcinoma are still unknown. We therefore retrospectively analyzed CT, FDG-PET, and histopathologic slides of surgical resected lung adenocarcinoma in 132 patients. Tumor characteristics on preoperative chest-CT, such as, GGO proportions, tumor diameters, and cavitation; FDG-PET SUV(max); and histopathologically determined differentiation degrees and tumor subtypes were evaluated. EGFR gene copy number status was categorized as FISH-positive or -negative. FISH-positivity was found in 53 patients (40.2%) and was significantly more frequent in tumors with a SUV(max)>7.0 (P=0.007). Furthermore, FISH-negativity was found to be more frequent in tumors with a GGO>50% (P=0.023) and diameter <15.5mm (P=0.006) on CT, or a well-differentiated histopathology (P=0.002). Moreover, the frequency of FISH-positivity increased as SUV(max) increased (P=0.0008) and as the proportion of GGO decreased (P=0.01). SUV(max)>7.0 was an independent predictor of FISH-positive results (odds ratio, 3.941; 95% CI, 1.691-9.182; P=0.01). In conclusion, a high SUV(max) on FDG-PET was significantly related to FISH-positive results. A high proportion of GGO, small tumor diameter on CT, and a well-differentiated histopathology were more frequent in FISH-negative adenocarcinomas.

Objectives: To investigate the role of maspin and p53 expression in the progression of gastric cancer, and its value as a prognostic indicator., Materials and Methods: The expression of maspin and p53 in 152 cases of gastric cancer was detected by immunohistochemistry and compared with the clinicopathologic tumor parameters. The relationship between maspin and p53 expression was also analyzed in the gastric cancers., Results: The positive expression rates for maspin and p53 in the cancers were 71.7% (109 of 152 cases) and 56.6% (86 of 152 cases), respectively. Two patterns of immunostaining for maspin were seen in the maspin-positive gastric cancer cases: cytoplasm-only staining (67.0%, 73 of 109 cases) and staining of both cytoplasm and nucleus (33.0%, 36 of 109 cases). Maspin expression showed a negative association with histologic grade, depth of invasion, metastasis, and TNM stage (all P<0.05). p53 expression showed an association with node metastasis, and TNM stage (both P<0.05). Maspin expression was negatively correlated with p53 expression (P<0.001, r=-0.291). In univariate log-rank analysis, loss of maspin expression, histologic grade, distant metastasis, and TNM stage were associated with patient survival. Interestingly, patients with nuclear and cytoplasmic maspin expression survived longer than those with only cytoplasmic expression. However, in multivariate analysis TNM stage and regional node metastasis were the only independent prognostic factors., Conclusions: Maspin expression might be an important factor in tumor progression and patient prognosis, but is not an independent prognostic factor. Maspin expression is inversely correlated with mutant p53 expression in gastric cancer, which suggests that maspin expression is regulated by the p53 pathway.

Objective: This study aims to evaluate the degree of inter- and intraobserver agreement when characterizing breast abnormalities using the Breast Imaging Reporting and Data System (BI-RADS)-ultrasound (US) lexicon, as defined by the American College of Radiology (ACR)., Materials and Methods: Two hundred ninety three female patients with 314 lesions underwent US-guided biopsies at one facility during a two-year period. Static sonographic images of each breast lesion were acquired and reviewed by four radiologists with expertise in breast imaging. Each radiologist independently evaluated all cases and described the mass according to BI-RADS-US. To assess intraobserver variability, one of the four radiologists reassessed all of the cases one month after the initial evaluation. Inter- and intraobserver variabilities were determined using Cohen's kappa (k) statistics., Results: The greatest degree of reliability for a descriptor was found for mass orientation (k = 0.61) and the least concordance of fair was found for the mass margin (k = 0.32) and echo pattern (k = 0.36). Others descriptive terms: shape, lesion boundary and posterior features (k = 0.42, k = 0.55 and k = 0.53, respectively) and the final assessment (k = 0.51) demonstrated only moderate levels of agreement. A substantial degree of intraobserver agreement was found when classifying all morphologic features: shape, orientation, margin, lesion boundary, echo pattern and posterior feature (k = 0.73, k = 0.68, k = 0.64, 0.68, k = 0.65 and k = 0.64, respectively) and rendering final assessments (k = 0.65)., Conclusion: Although BI-RADS-US was created to achieve a consensus among radiologists when describing breast abnormalities, our study shows substantial intraobserver agreement but only moderate interobserver agreement in the mass description and final assessment of breast abnormalities according to its use. A better agreement will ultimately require specialized education, as well as self-auditing practice tests.

Background: Recent studies have demonstrated that CDX-2 is expressed in the intestinal metaplasia of the stomach and intestinal-type gastric cancer. To address the role of CDX-2 in carcinogenesis of gastric carcinomas of intestinal type, the expression of CDX-2 in gastric carcinoma and precursor lesions were examined using immunohistochemistry., Methods: A total of 160 specimens diagnosed as gastric carcinomas or non-invasive neoplasia from 158 patients were analyzed for CDX-2 expression by immunochemical methods. Patients were classified into histopathologic subgroups according to the Padova international classification: 60 cases of low-grade non-invasive neoplasia, 55 cases of high grade, and 45 cases of invasive intestinal-type adenocarcinoma. The CDX-2 expression in non-neoplastic gastric mucosa including intestinal metaplasia was also evaluated in the areas included in the histologic sections., Results: The CDX-2 expression was localized in the epithelial cell nuclei in the area of intestinal metaplasia with or without dysplasia and carcinoma, consistent with its role as a transcriptional regulator. No CDX-2 reactivity was noted in the normal mucosa in all cases. The CDX-2 expression was detected in 73.3% of low-grade cases, 85.5% of high-grade cases and 91.1% of intestinal-type adenocarcinoma cases. In the gastric mucosa with intestinal metaplasia, 89.7% of the samples were positive. The CDX-2-expressing cells in intestinal metaplasia were more prevalent than in dysplasia and carcinoma. Expression of CDX-2 showed a statistically significant positive correlation with increasing grade of dysplasia and carcinoma., Conclusions: These findings suggest that CDX-2 expression in stomach cancer may be a marker of the progression of gastric carcinogenesis, and that its activation may represent an early event.

Objective: To evaluate the expression of tumor suppressor gene phosphatase and tensin homologue on chromosome 10 (PTEN) in ovarian epithelial tumors and its correlation with tumor growth and clinicopathologic features in ovarian adenocarcinomas., Study Design: Immunohistochemical staining with anti-PTEN antibody was performed in 54 adenocarcinomas and 23 borderline tumors of the ovary. The apoptotic cells were visualized by terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling, and proliferative cells were visualized by staining with Ki-67 antibody., Results: Reduced PTEN expression was significantly higher among the adenocarcinomas than the borderline tumors (p < 0.001). Reduced PTEN expression in adenocarcinomas did not correlate with International Federation of Obstetrics and Gynecology (FIGO) stage. The Ki-67 index (KI) and apoptotic index were significantly higher in adenocarcinomas as compared with borderline tumors (p < 0.001). Tumors with reduced PTEN expression in ovarian adenocarcinomas had a significantly higher KI than those with normal PTEN expression (p < 0.01). By univariate analysis, FIGO stage and histologic type correlated with survival. However, FIGO stage was the only independent prognostic factor by multivariate analysis., Conclusion: Our results suggest that alteration of the PTEN gene may be associated with malignant transformation of ovarian epithelial tumors. The PTEN gene seems to be a negative regulator of cell proliferation in ovarian adenocarcinomas.

Objective: The purpose of this study was to evaluate cyclooxygenase (COX)-2 expression in adenocarcinomas of the uterine cervix and its correlation with clinicopathologic features, angiogenesis, and tumor growth., Methods: Thirty-nine cases of FIGO clinical stage I and II adenocarcinoma of the uterine cervix were examined by immunohistochemical studies with anti-COX-2. Microvessels were immunohistochemically labeled with an antibody to CD34. Computerized image analysis was used to evaluate microvessel density (MVD). The apoptotic cells were visualized by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) and proliferative cells were visualized by staining with Ki-67 antibody., Results: Twenty-eight tumors (71.8%) were classified as COX-2 positive. COX-2 expression correlated with FIGO stage (P < 0.01). Tumors expressing COX-2 had a significantly higher MVD and Ki-67 index than those that did not express COX-2 (P < 0.05). However, COX-2 expression did not correlate with the apoptotic index. In univariate long-rank analysis, COX-2 expression, MVD, and FIGO stage were associated with shortened survival. However, FIGO stage and MVD were the only independent prognostic factors by multivariate analysis., Conclusions: Our results suggest that COX-2 expression in cervical adenocarcinomas may contribute to tumor progression by increasing angiogenesis and cell proliferation.

Background: Angiogenesis has been shown to be a critical aspect of tumor growth and progression. Vascular endothelial growth factor (VEGF) has potent angiogenic activity and has been identified in a wide variety of malignancies, including pancreatic carcinoma. The tumor-suppressor gene p53 has been thought to regulate VEGF in angiogenesis. The aim of the current study was conducted to investigate the association between p53 mutation and VEGF expression and the prognostic value of these factors in pancreatic carcinoma., Methods: Formalin-fixed, paraffin-embedded tissue specimens were obtained from 30 patients who underwent surgery for pancreatic carcinoma. We used an immunohistochemical technique to localize VEGF and p53 in pancreatic carcinoma tissues., Results: Positive expression of VEGF was detected in 17 out of 30 (56.7%) tumors. Positive expression of VEGF correlated with the depth of tumor invasion (p = 0.002). There was a trend towards an association between positive expression of VEGF and distant metastasis, although these associations were not statistically significant (p = 0.070). p53 mutations were identified in 18 out of 30 (60.0%) tumors. However, no significant correlation was found between p53 expression and various clinicopathological parameters. The correlation between p53 mutation and VEGF expression was statistically significant (p = 0.004)., Conclusion: VEGF, a key factor for the induction of tumor-associated angiogenesis, may be involved in tumor characteristics, including tumor invasion and metastasis. And p53 mutation may be implicated in the regulation of angiogenesis through a VEGF up-regulation.

Gastric cancer is common among the world, but genetic mechanisms of gastric carcinogenesis are not well understood. Gastric polypoid adenomas and flat dysplasias are regarded as precursor lesions. However, a detailed molecular study of these lesions has not been done to determine their role as precancerous lesions. We investigated mutations of the APC, beta-catenin, and K-ras genes, and microsatellite instability (MSI) status in 35 adenomas and 47 flat dysplasias without adenocarcinoma, 35 adenomas/dysplasias associated with adenocarcinomas, and 39 adenocarcinomas (20 diffuse type and 19 intestinal type). Somatic APC gene mutations were identified in 76% (59 of 78) of adenomas or flat dysplasias without associated adenocarcinoma, but in only 3% (1 of 30) of adenomas/dysplasias associated with adenocarcinoma, and in only 4% (3 of 69) of adenocarcinomas (P < 0.000001). No mutations of beta-catenin were found in adenocarcinomas, or adenomas/dysplasia without APC mutation. K-ras mutations were detected in 5% (4 of 82) of gastric adenomas/dysplasia without carcinoma, 3% (1 of 39) of adenocarcinomas without associated adenoma/dysplasia, and not in 32 adenocarcinomas with associated adenoma/dysplasia. High level of MSI (MSI-H) was more frequent in gastric adenoma/dysplasia associated with carcinoma (17%, 6 of 35) than in adenomas/dysplasia without carcinoma (3%, 2 of 75; P = 0.01). MSI-H was also more frequent in intestinal type adenocarcinoma (20%, 11 of 54) than in diffuse type (0%, 0 of 20; P = 0.03). APC gene mutations were present in six of nine (67%) of gastric adenomas/dysplasias with low level of MSI, but in none of the eight adenomas/dysplasia with MSI-H phenotype (P = 0.009). Our results indicate that somatic mutation of the APC gene plays an important role in the pathogenesis of gastric adenoma and dysplasia but has a limited role in neoplastic progression to adenocarcinoma. Gastric adenomas or dysplasias without APC mutations but with or without MSI may have a different biological behavior, and are precursors of intestinal-type of gastric adenocarcinomas.

Objective: The purpose of this study was to evaluate vascular endothelial growth factor (VEGF) expression in adenocarcinomas of the uterine cervix and its correlation with clinicopathologic features, angiogenesis, and expression of p53 and c-erbB-2 proteins., Methods: Thirty-seven cases of FIGO clinical stage I and II adenocarcinoma of the uterine cervix were examined by immunohistochemical studies with anti-VEGF, anti-CD34, anti-p53, and anti-c-erbB-2 antibodies. Computerized image analysis was used to evaluate microvessel density (MVD)., Results: Thirty-one tumors (83.8%) were classified as VEGF positive. Six tumors (16.2%) showed p53 protein expression while 11 tumors (29.7%) expressed the c-erbB-2 protein. MVD ranged from 13.3 to 44.8, with a median value of 25.5 (26.9 +/- 7.5). Tumors expressing VEGF had a significantly higher MVD than those that did not express VEGF (P < 0.05). VEGF expression was significantly associated with c-erbB-2 protein expression (P < 0.05). The spatial distributions of both VEGF expression and c-erbB-2 expression were similar in tumor tissues. In univariate log-rank analysis, stage (P = 0.0250), lymphovascular space invasion (P = 0.0156), and MVD (P = 0.0360) were associated with shortened survival., Conclusion: VEGF expression plays a role in promoting angiogenesis in cervical adenocarcinomas and c-erbB-2 is likely to be involved in the up-regulation of VEGF expression.

Tumor angiogenesis has been shown to be important for growth and metastasis in human neoplasms. Angiogenesis is usually determined by immunohistochemical staining of tumor tissue using various antibodies specific for endothelial cells. CD34 has been the one most commonly used in studies of tumor angiogenesis. Nestin, a class VI intermediate filament protein, was reported to be a good angiogenic marker in animal models. The aim of the current study was to compare the predictive value of angiogenesis as determined by CD34 and nestin on the same group of patients with advanced gastric carcinomas and to evaluate the possibility of nestin being a newer, better angiogenesis marker. Immunohistochemical staining using antinestin polyclonal antibody and anti-CD34 monoclonal antibody was carried out on surgical specimens from 61 patients with advanced gastric adenocarcinomas. The sensitivity of each of the two antibodies was evaluated by microvessel density (MVD) measurement by counting vessels in three 200x fields of intense neovascularization ("hot spots") of invasive tumors using a digital image analyzer. Immunoreactivity for nestin and CD34 was seen in the endothelial cells, and no stain was noted in the negative controls. MVD determined by nestin [87.74 +/- 29.30 (mean +/- standard deviation)] staining was significantly greater than that obtained by CD34 (82.48 +/- 32.27), and the difference was statistically significant. There was no correlation between MVD and patient clinical outcome with either antibody. Interestingly, in patients with larger carcinomas, MVD determined by nestin correlated better with longer survival than CD34. The difference was statistically significant. These results indicate that nestin is the better marker to evaluate neovascularity in endothelial cells. Evaluation of MVD determined by immunohistochemistry has limited value in patients with gastric carcinomas.

Background/aims: E-Cadherin and its associated cytoplasmic proteins, catenins, are important mediators of epithelial cell-cell adhesion and intracellular signaling. Much evidence exists suggesting a tumor invasion suppressor role for E-cadherin and catenins and loss of expression, as well as mutations, has been described in a number of epithelial cancers. The aim of this study was to evaluate the expression of E-cadherin and catenins in pancreatic adenocarcinoma tissue, and to examine the relationship between these expression and various clinicopathological parameters., Methods: In this study, we conducted an immunohistochemical investigation of expression of E-cadherin, alpha- and beta-catenins in 30 tissue samples obtained from pancreatic ductal adenocarcinoma patients undergoing surgical treatment., Results: In the pancreatic mucosa of noncancerous areas, epithelial cells showed equally strong membranous expression of E-cadherin, alpha- and beta-catenin proteins at the cell-cell boundaries. Reduced expression of E-cadherin, alpha- and beta-catenins was demonstrated in 60.0, 40.0, and 56.7% of cancer tissues, respectively. Reduced expression of E-cadherin, alpha- and beta-catenins correlated with tumor dedifferentiation (p = 0.012, 0.013, and 0.033, respectively). Reduced expression of E-cadherin correlated with stage and lymph node involvement (p = 0.031, 0.009, respectively). alpha-Catenin and beta-catenin expression did not correlate with the patient's age and sex, with the tumor size, location, stage and depth of invasion, or lymph node involvement and distant metastasis., Conclusion: These results suggest that the E-cadherin and catenins may be a useful marker of differentiation and prognosis in pancreatic adenocarcinoma, although the mechanisms underlying changes in E-cadherin and catenin expression are not fully known.

Background/aims: Cyclooxygenase-2 (COX-2) expression appears to be increased in several different types of human cancers, suggesting that the presence of COX-2 is associated with carcinogenesis. Recently, increased expression of COX-2 has been frequently detected in gastric cancer, and this may have prognostic significance. In the present study, we aimed to analyze the expression of COX-2 in a much larger sample to determine whether COX-2 expression is related to the clinicopathological features and survival rates of patients with gastric cancer., Methods: We investigated 140 patients with gastric cancer who underwent surgery between January 1992 and December 1993 and examined the expression of COX-2 in human gastric cancer tissue by immunohistochemistry., Results: COX-2 expression was present in the cytoplasm of tumor cells but not in normal gastric epithelia. Positive expression of COX-2 was detected in 86 of 140 gastric cancers analyzed (61.4%). Positive expression of COX-2 correlated with the depth of tumor invasion (p = 0.015). However, there was no association between COX-2 expression and tumor stage or status of lymph node or distant metastasis. Furthermore, COX-2 expression was not associated with patient survival (p = 0.816). Positive expression of COX-2 occurred more frequently in intestinal than in diffuse or mixed types of cancer and correlated with tumor differentiation (p < 0.001, p = 0.001, respectively)., Conclusion: These results suggest that COX-2 may play an important role in the evolution of gastric carcinogenesis and be associated with well-differentiated and intestinal type pathways in gastric carcinogenesis. However, COX-2 expression seems to be less useful for establishing prognosis for gastric cancer., (Copyright 2002 S. Karger AG, Basel)

It is well known that patients with neurofibromatosis have an increased incidence of various neoplasms, most of these being tumors of neural-crest origin, including neurofibromas, leiomyomas, ganglioneuromas, paragangliomas, and carcinoids. However, the occurrence of small-bowel adenocarcinoma is rare. In this article, we report a patient with small-bowel adenocarcinoma, the seventh such reported case. We include a review of the literature and a brief discussion of the implications of this association. We suggest that the association between small-bowel adenocarcinomas and neurofibromatosis may not be fortuitous, and that small-bowel adenocarcinoma should be considered, in particular. in the differential diagnosis of gastrointestinal symptoms in patients with neurofibromatosis. Also, a definite histologic diagnosis must be made, with the employment of special staining techniques, because of the differing prognoses for various cell types.