Invasive Tumor Size Research Articles

Abstract P5-22-15: Hormone receptor status is a predictive factor for axillary lymph node recurrence after sentinel lymph node biopsy

Abstract Background Axillary staging is important for predicting prognosis, and for local control in early breast cancer. Sentinel lymph node biopsy (SLNB) is a widely accepted method to avoid unnecessary axillary lymph node dissection (ALND). Since the ACOSOG Z0011 trial was published, we have refrained from ALND for selected patients with positive SLNB results. However, some cases have shown regional lymph node recurrences after SLNB without axillary dissection. The purpose of this study is to identify risk factors for recurrences, to ensure a safe axillary surgery. Methods A retrospective review of 1011 patientswho underwent SLNB without ALND between June 2004 and March 2017 was performed. Since October 2012, we have not performed ALND in patients (a) with 1 or 2 positive sentinel lymph nodes (SLNs), (b) with positive SLNs that are unmatted or not gross extra nodal extension, (C) in whom clinical tumor size is <5 cm, and (d) who receive adjuvant endocrine therapy or chemotherapy and radiotherapy. Cases of mastectomy, lumpectomy with a positive margin and additional resection or boost radiotherapy, and bilateral cancer were included. SLNs were identified using technetium sulfur colloid and indigo carmine blue dye, and were bisected in parallel to the long axis of the nodes. The sections were stained with hematoxylin and eosin. Adjuvant systemic and/or radiation treatment was delivered as per the National Comprehensive Cancer Network and the Japanese Breast Cancer Society clinical practice guidelines and was based on the patients' pathological and clinical traits. Results Of the 1011 patients, 969 had negative and 42 had positive SLNs. The median age of patients was 59 years (range 21-88). The median invasive breast tumor size was 15 mm (range 0.05-85), with 1.9% tumors being pathological T3 lesions; 127 patients (12.3%) developed lymphatic vessel invasion. SLNs identification rate was 99.4%. The median number of SLNs removed per patient was 2 (range 1-7). After follow-up of a median 78.5 months, 10 patients (1.0%) had an axillary recurrence and all of them had negative SLN metastasis. The median time to axillary recurrence was 26 months (range 9-94). The hormone receptor (HR) status was significantly related to axillary recurrence (p=0.008). While triple negativity had a tendency to relate (p=0.06), human epidermal growth factor receptor 2 (HER2) status did not correlate with axillary recurrence (p=0.13). Tumor subtypes and axillary recurrence SLNB without ALND (n=1011)Axillary recurrenceP valueHR positive72650.009HR negative1615 HER2 positive12130.13HER2 negative7667 Triple Negative10030.06Not Triple Negative7877 DCIS1240 DCIS: Ductal carcinoma in situ Conclusions As reported previously, the axillary recurrence rate after SLNB was low. Our results show that HR negativity was a significant factor for axillary recurrence. Although the ACOSOG Z0011 trial criteria focused on ALNB positive cases, they do not mention the tumor subtypes. Our findings show that HR negative patients without ALND have to follow up carefully. Citation Format: Sekine C, Nakano S, Mibu A, Otsuka M, Oinuma T. Hormone receptor status is a predictive factor for axillary lymph node recurrence after sentinel lymph node biopsy [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-22-15.

Expression and clinical correlation of NGAL and VEGF in endometrial carcinoma.

To determine the expression of neutrophil gelatinase-associated lipocalin (NGAL) and vascular endothelial growth factor (VEGF) in endometrial carcinoma. The clinical features (FIGO staging, pathological type, differentiation level, myometrial invasion depth and tumor size) and immunostaining analysis of endometrial carcinoma (30 cases), atypical hyperplasia (30 cases) and proliferative endometrial tissues (30 cases) were analyzed. Immunohistochemistry and reverse transcription PCR (RT-PCR) were performed to detect the expression of NGAL and VEGF. The positive tissue immunostaining and mRNA expression of NGAL and VEGF in endometrial carcinoma were significantly higher than in either atypical hyperplasia or proliferative endometrial tissues (p<0.05). The relative expression level of NGAL and VEGF was positively correlated with worse FIGO staging, higher differentiation level and a greater myometrial invasion depth (p<0.05); but not with patient age, pathological type or tumor size (p>0.05). The abnormal high expression of NGAL and VEGF observed in the endometrial carcinoma may be an important biomarker for early tumor diagnosis or as a novel target for therapeutic intervention.

Clinical significance of primary tumor score determined by tumor depth and size in patients with resectable gastric cancer.

Although postoperative management of gastric cancer is determined by pathological stage based on the tumor-node-metastasis classification, predicting disease recurrence and prognosis in patients undergoing gastrectomy is clinically difficult. We investigated the depth of tumor invasion and tumor size in resected specimens from patients with gastric cancer and assessed the clinical utility of primary tumor score (PTS) calculated by tumor depth and size as a prognostic marker. We classified 247 patients with gastric cancer into three groups based on cut-off values for deeper tumor invasion (pT2–T4) and larger tumor size (≥ 45 mm) as a PTS of 2 (both abnormalities), 1 (one abnormality), or 0 (neither abnormality). PTS correlated significantly with lymph node metastasis, lymphovascular invasion, and stage (P < 0.0001 each). Survival differences among groups based on PTS were significant (P < 0.0001). Multivariate analysis identified PTS alone as an independent prognostic factor (P = 0.0363). PTS derived from primary tumor information alone is a potentially useful marker for predicting tumor progression and prognosis in postoperative patients with gastric cancer.

Erinacine Facilitates the Opening of the Mitochondrial Permeability Transition Pore Through the Inhibition of the PI3K/ Akt/GSK-3β Signaling Pathway in Human Hepatocellular Carcinoma

Background/Aims: Erinacine, which is extracted from the medicinal mushroom Hericium erinaceus, is known to play anticancer roles in human cancers. The following study aims to investigate the role of erinacine in the opening of the mitochondrial permeability transition pore (MPTP) in hepatocellular carcinoma (HCC) through the PI3K/Akt/GSK-3β signaling pathway and highlights the applicability of erinacine in HCC treatments. Methods: HCC and paracancerous tissues were obtained from 85 HCC patients who’ve undergone surgical resection. Immunohistochemistry was adopted to detect positive expression of PI3K, Akt, and GSK-3β. Treatment of HepG-2 with LY294002 (an inhibitor of the PI3K/Akt/GSK-3β signaling pathway) and different concentration of erinacine was performed to determine the involvement of LY294002 in erinacine action. The expressions of PI3K, Akt, GSK-3β, CyclinD1, Vimentin, β-catenin, Bcl-2, E-cadherin, Bax, and caspase-9 were determined by RT-qPCR and Western blot analysis. Cell viability, colony formation rate, migration, invasion, cycle, and apoptosis were detected by MTT, colony formation, wound healing assay, Transwell assay, and flow cytometry, respectively. The size and weight of xenograft tumors were observed in nude mice. Mitochondrial membrane potential in HepG-2 was determined using laser scanning confocal microscopy following JC-1 staining. Mitochondrial Ca2+ indicator Rhod-2, AM was used to detect the changes of mitochondrial Ca2+, while western blot analysis was employed to detect the presence levels of cytochrome C (cyt-C). Results: The results revealed that PI3K, Akt, and GSK-3β were up-regulated in HCC tissues. Erinacine or LY294002 led to a decrease in mitochondrial membrane potential, increase in intracellular mitochondrial Ca2+, and the release of cyt-C in mitochondria. In addition, Erinacine was found to decrease the mitochondrial membrane potential, expression of PI3K, Akt, GSK-3β, CyclinD1, Vimentin, β-catenin, and Bcl-2, cell proliferation, colony formation ability, migration, invasion, and xenograft tumor size, while E-cadherin, Bax, and caspase-9 expression, and cell apoptosis were elevated in a dose-dependent manner. Erinacine also stimulated the effects of LY294002 on the HCC. Following the addition of 500 μM Erinacine and MPTP opening inhibitor CsA, we found that the mitochondrial membrane potential level increased, while mitochondrial Ca2+ and Cyt-C decreased from the mitochondria. Conclusion: The results from the study demonstrated that erinacine induced MPTP opening, facilitates the release of cyt-C, and inhibited cell proliferation, migration, and invasion, while it promotes apoptosis by inactivating the PI3K/Akt/GSK-3β signaling pathway, preventing the progression of HCC.

WISP1 genetic variants as predictors of tumor development with urothelial cell carcinoma

ObjectivesUrothelial cell carcinoma (UCC) of the urinary bladder is a major malignancy of the genitourinary tract. Etiological factors, such as the environment, ethnicity, genetics, and diet, contribute to UCC carcinogenesis. WNT1-inducible signaling pathway protein 1 (WISP1), also known as CCN4, a cysteine-rich protein belonging to the Cyr61, CTGF, Nov (CCN) family of matricellular proteins, has many developmental functions and might be involved in carcinogenesis. This study investigated WISP1 single-nucleotide polymorphisms to evaluate UCC susceptibility and clinicopathological characteristics. Materials and methodsReal-time polymerase chain reaction was used to analyze 4 single-nucleotide polymorphisms of WISP1 in 369 patients with UCC and 738 controls without cancer. ResultsThe results showed that in 128 women with UCC who carried WISP1 rs2929973 (AG + GG) variants had a higher risk of developing an advanced muscle-invasive tumor stage (pT2–pT4, P = 0.007) and a large tumor (T1–T4, P = 0.030). Further analyses revealed that a correlation between the expressions of WISP1 and invasive tumor and large tumor size in urothelial carcinoma was observed in the TCGA (The Cancer Genome Atlas) dataset. ConclusionsOur results indicated that patients with UCC carrying rs2977530 genetic variants (AG + GG) have a higher risk of developing a more invasive tumor stage and a large tumor. WISP1 polymorphisms may serve as a marker or a therapeutic target in UCC.

P2.01-018 Risk Factors in Patients with Pathological N1 or N2 Non-Small Cell Lung Cancer

Pathological (p) N1 or N2 non-small cell lung cancer (NSCLC) patients may experience poor prognosis despite complete resection; therefore, adjuvant chemotherapy is recommended for them. In this study, we investigated the risk factors for pN1 or N2 NSCLC. From March 2005 to December 2015, we retrospectively reviewed 93 patients with completely resected pN1 or N2 NSCLC. Patients with synchronous or metachronous multiple lung cancer, malignancies from other organs, or who received neoadjuvant chemoradiotherapy were excluded. Clinicopathological factors analyzed included: age, sex, serum carcinoembryonic antigen levels, surgical procedures, histology, size of invasive tumor, pathological N status, pleural invasion, lymphatic invasion, vascular invasion, and histological grade. Univariate and multivariate analyzes of disease-free survival and overall survival were conducted. The study group comprised 93 patients (64 men, 29 women; age range: 38–86 years; mean: 68±9.9 years). The median follow-up period was 35.1 months. The preoperative serum carcinoembryonic antigen level was elevated in 36 patients. Complete resection was performed in all patients, comprising pneumonectomy in two patients (including sleeve pneumonectomy), bilobectomy in three, and lobectomy in 87 (including lobectomy with bronchoplasty or resection adjacent organs). Adenocarcinoma, squamous cell carcinoma, and other histology were observed in 59, 22, and 12 patients, respectively. The maximum diameter of invasive diameter was >30 mm in 39 patients and ≤30 mm in 54. There were 52 patients with pN1 and 41 with pN2. Forty-four were with pleural invasion, 52 with lymphatic invasion, and 48 with vascular invasion. Multivariate analysis showed histology to be an independent factor for recurrence, whereas older age (>70 years), pleural invasion, and adjuvant chemotherapy were independent factors for poor survival. There were 24 patients with no adjuvant chemotherapy, 10 could not receive it because of poor postoperative performance status, and 3 were ineligible because of older age. The 5-year overall survival in patients with adjuvant chemotherapy was 61.8%, compared with 23.8% for those without (p =0.002). Older age, pleural invasion, and adjuvant chemotherapy were found to be independent factors for poor survival in pN1 or N2 NSCLC. Adjuvant chemotherapy is a potential consideration for pN1 or N2 patients. Surgery to maintain performance status may be useful in relation to undergoing adjuvant chemotherapy.

ES 01.02 New Histological Classification

ES 01.02 New Histological Classification

PTis and pT1a Ipsilateral Breast Tumor Recurrence Is Associated with Good Prognosis after Salvage Surgery

Objectives: Patients with ipsilateral breast tumor recurrence (IBTR) after breast-conserving surgery have a poor prognosis. There is little information regarding the prognostic impact of the tumor size in patients with IBTR. Methods: A total of 143 patients who had histologically confirmed IBTR without distant metastases and who underwent salvage surgery between 1989 and 2013 in our hospital were included. Distant disease-free survival (DDFS) was calculated according to the invasive tumor size of IBTR. The median follow-up period was 4.6 years. Results: Patients with pT1b or more advanced IBTR have a high (≥20%) 5-year distant recurrence risk. There were significant differences in DDFS between patients with pTis or pT1a and those with pT1b or a more advanced stage (5-year DDFS: 94.4 vs. 70.1%, respectively, p value = 0.006). This significance remained after adjusting for other clinicopathological factors (p value = 0.04). Conclusion: Patients with pTis or pT1a IBTR have a good prognosis after salvage surgery for IBTR, and the omission of adjuvant chemotherapy could be considered. Further research and validation studies are needed.

Association of conventional ultrasound, elastography and clinicopathological factors with axillary lymph node status in invasive ductal breast carcinoma with sizes > 10 mm.

BackgroundTo evaluate whether conventional ultrasound, elastography [conventional strain elastography of elasticity imaging, acoustic radiation force impulse induced strain elastography of virtual touch tissue imaging, and a novel two-dimensional shear wave elastography of virtual touch tissue imaging quantification] and clinicopathological factors are associated with axillary lymph node metastasis in invasive ductal breast carcinoma with sizes > 10 mm.Materials and MethodsWe evaluated 150 breast lesions from 148 patients using the above methods and the clinicopathological factors. Univariate and multivariate logistic regression analysis were performed to determine the axillary lymph node metastasis risk factors. Diagnostic performance was evaluated using receiver operating characteristic curve analysis.ResultsSixty-three tumors (42%) were node-positive, 87 (58%) were node-negative. Aspect ratio, virtual touch tissue imaging grade, shear wave velocity, pathological invasive tumor size, and histological grade maintained independent significance in predicting nodal involvement. The mean tumor shear wave velocitys (4.60, 6.49, 7.16) increased in proportion to metastatic node number (0, 1–3, ≥ 4, respectively; P < 0.001). For all tumors in this study, the cut-off shear wave velocity was 6.16 m/s and was associated with 64.1% sensitivity, 78.0% specificity and an area under the ROC curve of 0.799 (95% confidence interval, 0.731–0.868).ConclusionsAspect ratio, virtual touch tissue imaging grade, shear wave velocity, pathological invasive tumor size and histological grade are independently associated with axillary lymph node metastasis in invasive ductal breast carcinoma with sizes > 10 mm.

Abstract 676: Nuclear expression of insulin receptor (InsR) adds prognostic information in primary breast cancer patients with high BMI

Abstract Aim and introduction The aim of this study was to elucidate the prognostic importance of nuclear expression of the insulin receptor (nucInsR) in primary breast cancer. The InsR is important for the metabolism, for the insulin-like growth factor (IGF) signaling network and is implicated in breast cancer. Insulin and InsR are interlinked with obesity and body mass index (BMI), which are also associated with breast cancer. The InsR is present both in the membrane and cytoplasm and can additionally translocate to the nucleus. The role of nucInsR is not well understood and the prognostic importance is unclear. Methods The tumor-specific expression of nucInsR was evaluated by immunohistochemistry on invasive breast cancer tissue microarrays from 984 primary breast cancer patients included in a population-based cohort in Sweden. Patients were followed for up to 11 years, the median follow-up for patients still at risk was five years. nucInsR in relation to prognosis was analyzed using Cox regression, adjusted for age, invasive tumor size, axillary lymph node involvement, histological grade, estrogen receptor (ER) status, BMI, tumor storage time, and treatment. Results Status for nucInsR was available for 900 patients (91.5%). nucInsRpos staining was present in 214 patients (23.8%) and was associated with lower age (P=0.004), and lower waist-to-hip ratio (P=0.006), but not with BMI, ER or PR status. During follow-up, 107 patients had a first breast cancer event. nucInsR had no prognostic significant impact among all patients. However, there was a significant effect modification of BMI on nucInsR regarding event-free survival (Pinteraction=0.006). Patients with nucInsRpos-expressing tumors and higher BMI (≥25 kg/m2) had lower risk for any breast cancer event, adjusted HR (0.49; 95% CI 0.26-0.93), while patients with nucInsRpos-expressing tumors and normal BMI (&amp;lt;25 kg/m2) were associated with a non-significant higher risk of events, adjusted HR (1.72; 95% CI 0.93-3.17). Conclusions These results indicate that nucInsR status may add prognostic information in primary breast cancer depending on BMI. Citation Format: Sofie Björner, Ann H. Rosendahl, Maria Simonsson, Andrea Markkula, Karin Jirström, Signe Borgquist, Carsten Rose, Christian Ingvar, Helena Jernström. Nuclear expression of insulin receptor (InsR) adds prognostic information in primary breast cancer patients with high BMI [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 676. doi:10.1158/1538-7445.AM2017-676

Can Tumor Biology Predict Occult Multifocal Disease in Breast Cancer Patients?

The SHAVE trial is a prospective trial in which 235 women with stage 0 to 3 disease undergoing partial mastectomy were randomized intraoperatively to either have cavity shave`s (CSMs) taken at the time of initial surgery or not. In this study, 9 of the 76 patients (11.8%) with initially negative margins randomized to the "shave" group had occult cancers found in the CSM. Seven of these patients had sufficient primary tumor tissue available for further analysis. These patients were age and stage matched in a 1:2 ratio to other patients in the trial who had no further disease found in their CSM. A tissue microarray was created, stained for E-cadherin, MUC1, and beta-catenin, and evaluated by two independent pathologists (blinded to outcome). There were no significant differences between cases and controls in terms of median invasive tumor size, ductal carcinoma in situ size, volume of initial resection, and volume of CSM. Further, no differences were noted between cases and controls for median (staining intensity × per cent of cells staining) for each marker. Hence, although nearly 12 per cent of breast cancer patients with negative margins will have occult disease, this could not be predicted by primary tumor markers in this study.

Semiquantitative Assessment of Tumor Spread through Air Spaces (STAS) in Early-Stage Lung Adenocarcinomas

IntroductionTumor spread through air spaces (STAS) has recently been reported as a form of tumor invasion having an unfavorable prognosis, but the significance of a small amount of STAS is not known. The aim of this study was to perform a semiquantitative assessment of STAS. MethodsSmall (≤2 cm) stage I lung adenocarcinomas surgically resected at our institution between 2003 and 2009 were assessed semiquantitatively in the most prominent area as no STAS, low STAS (1–4 single cells or clusters of STAS), or high STAS (≥5 single cells or clusters of STAS) by using a 20× objective and a 10× ocular lens. A statistical analysis was performed to determine the impact of clinicopathologic parameters on STAS and to clarify the relationship between STAS and patient survival. ResultsSTAS was assessed as no STAS in 109 of 208 cases (52.4%), as low STAS in 38 cases (18.3%), and as high STAS in 61 cases (29.3%). There were statistically significant associations between higher STAS and solid predominant invasive adenocarcinoma (p < 0.001), pleural invasion (p < 0.001), lymphatic invasion (p < 0.001), vascular invasion (p < 0.001), and tumor size of 10 mm or more (p = 0.037). There was a significant association between increasing STAS and shorter recurrence-free survival (RFS) in univariate analysis (no STAS, 154.2 months; low STAS, 147.6 months; and high STAS, 115.6 months). In a multivariate Cox proportional hazards model, only STAS (p = 0.015) remained a significant predictor of RFS. ConclusionsWe found that one-third of resected small adenocarcinomas had high STAS. Higher STAS was predictive of worse RFS.

Incidence of Lymph Node Metastasis in Surgically Staged FIGO IA G1/G2 Endometrial Cancer With a Tumor Size of More Than 2 cm.

The study aims to investigate effect of tumor size on lymphatic spread in patients with low-risk endometrial cancer (EC). This study included patients with EC who underwent staging surgery with systematic lymphadenectomy between 2002 and 2015 at the Hacettepe University Hospital. Patients with grade 1 or 2 endometrioid type tumor who had 50% or lower myometrial invasion were included. Patients who had no myometrial invasion or had uterine high-risk features (nonendometrioid histology, grade 3, and deep myometrial invasion) were excluded. The study group consisted of 191 patients, and the mean age of the patients was 57.8 years. Of these patients, 124 (64.9%) had tumor size of more than 2 cm and 67 (35.1%) had tumor size of 2 cm or less. Lymph node metastasis was detected in 12 (9.7%) of the 124 patients with tumor size of more than 2 cm. On the other hand, none of the 67 patients (0%) with tumor size of 2 cm or less was found to have lymphatic involvement. Of the factors analyzed for correlation with lymph node metastasis in patients with low-risk EC, the presence of lymphovascular space invasion (LVSI) and primary tumor size were found to be significant predictors of lymphatic spread in univariate analysis (P < 0.001 and P = 0.009, respectively). In multivariate analysis, tumor size (odds ratio, 6.86; 95% confidence interval, 1.007-infinite; P < 0.05) and LVSI (odds ratio, 14.261; 95% confidence interval, 3.4-59.6; P < 0.001) were 2 independent predictors associated with lymphatic involvement. Our trial supports that tumor size of more than 2 cm and LVSI are 2 independent factors for lymph node metastasis in patients with low-risk EC. Both factors can be used together to select patients with traditional low-risk histologic features who would absolutely benefit from lymph node dissection.

Abstract P3-14-06: A single-center report of 125 cases of incidental internal mammary lymph node biopsy in free abdominal flap breast reconstruction

Abstract P3-14-06: A single-center report of 125 cases of incidental internal mammary lymph node biopsy in free abdominal flap breast reconstruction

Comparison of Prognosis of Solid and Part-Solid Node-Negative Adenocarcinoma With the Same Invasive Component Size

Our study compared the prognosis of solid node-negative adenocarcinoma sized less than 20mm with that of part-solid node-negative adenocarcinoma with an invasive tumor size of less than 20 mm. From 2003 to 2012, 191 patients were selected with a diagnosis of solid or part-solid pathologic node-negative adenocarcinoma with an invasive component sized less than 20 mm. The enrolled patients were categorized into two groups: group 1 had solid adenocarcinoma consisting only of the invasive component, and group 2 had part-solid adenocarcinoma consisting of both an in situ and an invasive component. Recurrence-free survival and overall survival at 5 years were compared using Kaplan- Meier survival analysis and the log-rank test. The mean size of the invasive component was 15.9 mm in group 1 (n= 92) and 15.2 mm in group 2 (n=99; p= 0.06), and the mean total lesion size was 15.9mm in group 1 and 21.0 mm in group 2 (p < 0.001). The median follow-up duration was 54.2 months. The 5-year overall survival rates were 90.3% in group 1 and 93.8% in group 2 (p= 0.160), and the recurrence-free survival rates were 84.0% in group 1 and 93.7% in group 2 (p=0.037). Lymphovascular invasion and high maximum standardized uptake values were significantly more common in group1. Although the total size of the part-solid adenocarcinoma lesions was larger than that of the solidadenocarcinoma lesions, the prognosis of part-solid adenocarcinoma was better than that of solid adenocarcinoma in cases of node-negative adenocarcinoma with invasive components sized less than 20 mm.

P1.03-084 Implications of 8th Edition TNM Proposal: Invasive vs. Total Size for T Descriptor in pT1a-2bN0M0 Lung Adenocarcinoma

The aim of this study was to conduct a clinicopathological comparative analysis of total tumor versus invasive tumor size in pT1a-2bN0M0 nonmucinous lung adenocarcinomas. Resected pT1a-2bN0M0 lung adenocarcinomas (1995-2012) based on 8th edition of TNM classification using total (N=1475) and invasive tumor size (N=1482) were included. Recurrence free probability [RFP] and lung cancer-specific survival [LCSS]) were compared between both pT-staging systems using Kaplan-Meier method. Use of invasive size for the T descriptor increased the number of pT1a tumors by 2 fold compared to use of total tumor size (316 vs. 161), with no difference in RFP and LCSS (RFP, 82% vs. 80%; LCSS, 94% vs. 93%). Use of invasive rather than total size also showed better stratification of lymphatic/vascular invasion and high-grade histological subtypes according to increasing pT stage. RFP and LCSS in invasive-size-based pT2b were lower than those in total-size-based pT2b (RFP, 44% vs. 60%; LCSS, 69% vs. 77%). In pT1a-2bN0M0 nonmucinous lung adenocarcinoma, the 8th edition TNM proposal to use invasive rather than total size for the pT descriptor gives better prognostic discrimination by capturing a larger number of patients with favorable prognosis (pT1a) and providing better stratification for pT2b.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Recurrence Pattern of Pathologic Stage I Lung Adenocarcinoma With Visceral Pleural Invasion

Visceral pleural invasion (VPI) is well known to be a poor prognostic factor in lung adenocarcinoma. There were few studies reporting postoperative recurrence pattern in lung adenocarcinoma with VPI. This study was to evaluate the clinical effect of VPI on recurrence pattern in pathologic stage I lung adenocarcinoma after curative resection. Among 574 patients with pathologic stage I lung adenocarcinoma after complete resection between 2003 and 2012, the clinicopathologic characteristics of 89 patients (16%) who had recurrence were retrospectively reviewed. The pathologic findings, postrecurrence survival, and patterns of recurrence were compared between patients with VPI and without VPI. Median follow-up duration was 53.6 months. The VPI was found in 43 patients (group I) and not found in 46 patients (group II). Both total tumor size and invasive size were larger in group I (3.2 versus 2.7 cm and 2.5 versus 2.1 cm; p < 0.05). The median duration of overall survival was 58 months in group I and 76 months in group II. As patterns of recurrence, pleural seeding was found in 25 patients, and the percentage of pleural seeding was significantly higher in group I than group II (44.2% versus 13.0%; p= 0.001). In group I, bilateral lung metastasis was significantly common (39.5% versus 13.0%; p= 0.004), and increasing percentage of pleural seeding was observed as the invasive tumor size grows. The presence of VPI was a significant predictable factor for pleural seeding and bilateral lung metastasis as patterns of recurrence after complete resection in pathologic stage I lung adenocarcinoma.

A SEER Database Analysis of the Survival Advantage of Transarterial Chemoembolization for Hepatocellular Carcinoma: An Underutilized Therapy

PurposeTo measure transarterial chemoembolization utilization and survival benefit among patients with hepatocellular carcinoma (HCC) in the Surveillance, Epidemiology, and End Results (SEER) patient population. Materials and MethodsA retrospective study identified 37,832 patients with HCC diagnosed between 1991 and 2011. Survival was estimated by Kaplan–Meier method and compared by log-rank test. Propensity-score matching was used to address an imbalance of covariates. ResultsMore than 75% of patients with HCC did not receive any HCC-directed treatment. Transarterial chemoembolization was the most common initial therapy (15.9%). Factors associated with the use of chemoembolization included younger age, more HCC risk factors, more comorbidities, higher socioeconomic status, intrahepatic tumor, unifocal tumor, vascular invasion, and smaller tumor size (all P < .001). Median survival was improved in patients treated with chemoembolization compared with those not treated with chemoembolization (20.1 vs 4.3 mo; P < .0001). Similar findings were demonstrated in propensity-scoring analysis (14.5 vs 4.2 mo; P < .0001) and immortal time bias sensitivity analysis (9.5 vs 3.6 mo; P < .0001). There was a significantly improved survival hazard ratio (HR) in patients treated with chemoembolization (HR, 0.42; 95% confidence interval, 0.39–0.45). ConclusionsPatients with HCC treated with transarterial chemoembolization experienced a significant survival advantage compared with those not treated with transarterial chemoembolization. More than 75% of SEER/Medicare patients diagnosed with HCC received no identifiable oncologic treatment. There is a significant public health need to increase awareness of efficacious HCC treatments such as transarterial chemoembolization.

COL11A1 is overexpressed in gastric cancer tissues and regulates proliferation, migration and invasion of HGC-27 gastric cancer cells invitro.

The role of COL11A1 in carcinogenesis is increasingly recognized. However, the biological role and potential mechanisms of COL11A1 in gastric cancer have not been elucidated. In the present study, the COL11A1 mRNA expression in 57patients with gastric cancer was measured by reverse transcription quantitative PCR (RT-qPCR), and the biological effects of COL11A1 suppression were determined using MTS, monolayer colony formation, flow cytometry and Transwell assays. In addition, the potential molecular mechanisms of COL11A1 in gastric cancer were analyzed by western blotting and cDNA microarray analysis. Compared with matched adjacent non-tumor tissue, COL11A1 mRNA was significantly overexpressed in tumor tissue and was positively related to age, tumor invasion depth, tumor size and lymph node positivity. Moreover, invitro experiments demonstrated that COL11A1 suppression by short hairpin RNA (shRNA) significantly inhibited the proliferation, migration and invasion of HGC-27 cells and that COL11A1 suppression promoted cell apoptosis, induced G1-phase cell cycle arrest and led to a significant downregulation of cyclinD1 and upregulation of p21 and cleaved caspase-3. In addition, the cDNA microarray analysis of HGC-27 cells with and without COL11A1 suppression indicated that COL11A1 may regulate multiple genes responsible for cell growth and/or invasion, including downregulation of CDK6, TIAM1, ITGB8 and WNT5A and upregulation of RGS2 and NEFL following suppression of COL11A1 expression in HGC-27 cells, validated with RT-qPCR assays. Taken together, our findings demonstrate that COL11A1 might be an oncogene in GC and is a promising therapeutic target in cancer treatment.

Incidental internal mammary lymph node biopsy in 113 cases of breast cancer undergoingfree abdominal flap breast reconstruction and its influencing factors

Objective: The aim of the current study is to determine the clinical value of incidental internal mammary lymph node biopsy in free abdominal flap breast reconstruction using internal mammary vessels as recipient vessels and to investigate the risk factors of internal mammary lymph nodes metastasis. Methods: The clinical data of all patients who underwent free abdominal flap breast reconstruction using internal mammary vessels as recipient vessels from November 2006 to December 2015 in the Department of Breast Surgery, Fudan University Shanghai Cancer Center were reviewed in the study. The incidence of internal mammary lymph node biopsy and the rate of metastasis were analyzed. Statistical analysis was conducted to evaluate the risk factors of internal mammary lymph node metastasis. Results: A total of 113 patients met the inclusion criteria, 53 (46.9%) of whom had internal mammary lymph nodes harvested. Four of these were positive for metastatic disease, all in immediate breast reconstructions. The incidence of metastasis was 7.5% in patients who had successful internal mammary lymph node biopsies.The multi-variate Logistic regression analysis showed that invasive tumor size, tumor location and axillary lymph node metastasis were not risk factors for internal mammary lymph node metastasis (P>0.05). Conclusions: Internal mammary lymph nodes found incidentally during recipient vessel exposure may provide important information about internal mammary lymph node metastasis in free flap breast reconstruction. This approach for internal mammary lymph node biopsy reveals an appreciable success rate and is convenient in clinical practice. The size of invasive tumor and the axillary lymph node metastasis are probably associated with internal mammary lymph node positivity.