Degree Of Tumor Invasion Research Articles

Prognostic implications of tumor-infiltrating lymphocytes within the tumor microenvironment in gastric cancer

Tumor-infiltrating lymphocytes (TILs) play a regulatory role in the tumor-associated immune response and are important in the prognosis and treatment response of several cancers. However, because of its heterogeneity, the prognostic value of TILs in gastric cancer (GC) is still controversial. Thus, this study aimed to investigate the association between the density of TILs and patients' outcomes in GC. Patients with gastric adenocarcinoma who underwent curative intent gastrectomy were retrospectively investigated. The groups for analysis were determined on the basis of TIL intensity and percentage of CD3+T-cell infiltration by immunohistochemical. Furthermore, Epstein-Barr virus (EBV), microsatellite instability (MSI), T-cell ratio of CD4 to CD8, and programmed death protein ligand 1 (PD-L1) status were evaluated. A total of 345 patients were enrolled: 124 patients with GCs (35.9%) were classified as the low-CD3+TIL group, and 221 patients with GCs (64.1%) were classified as the high-CD3+TIL group. Poorly differentiated histology (P=.014), EBV-positive status (P<.001), PD-L1-positive status (P=.001), and CD4<CD8 (P<.001) were associated with high-CD3+GC. There was no difference regarding MSI status, the degree of tumor invasion (pT), the presence of lymph node metastasis, and pTNM stage between low- and high-CD3+groups. In survival analysis, the high-CD3+group had better disease-free survival and overall survival rates than had the low-CD3+group (P=.055 and P=.041, respectively). In the multivariate analysis, total gastrectomy, lymph node metastasis, advanced pT stage, and low CD3+levels were independent factors related to worse survival. High CD3+TILs levels were significantly associated with improved survival and could serve as prognostic biomarkers in GC. In addition, CD3+T-cell infiltration was related to both EBV-positive and PD-L1-positive GC and may assist in the investigation of targets in immunotherapy.

Association of CCND1 Gene Polymorphism rs9344 with Grade and Invasion Degree of Colorectal Cancer at Prof. Dr. I.G.N.G. Ngoerah Central General Hospital

The majority of colorectal cancer (CRC) are sporadic CRC that can be caused by genetic variations such as Single Nucleotide Polymorphisms (SNPs). The CCND1 gene polymorphism rs9344 could involve at the beginning and the development of CRC. This study aimed to analyze the association between CCND1 gene polymorphism rs9344 with the grade and invasion degree of colorectal cancer in at Prof. Dr. I.G.N.G. Ngoerah Central General Hospital, Denpasar, Bali. This cross-sectional study was carried out at the Integrated Biomedical Laboratory Unit, Faculty of Medicine, Udayana University. Data analysis of 32 samples showed majority age was above 50 years old as many as 28 (87.5%), with men as 21 samples (65.6%). Histopathology description was adenocarcinoma in 32 samples (100%). Grading histopathology low grade was 31 samples (96.6%). The degree of tumor invasion was high as 25 samples (78.1%). From the aspect of pathological stage pNx as much as 27 (84.4%). The majority location of tumors was on the left side as 21 samples (65.6%). The polymorphisms of CCND1 rs9344 genotype sequentially AA as 20 samples (62.5%), AG as 9 samples (28.1%), while GG as 3 samples (9.4%). The statistical analysis found that CCND1 gene polymorphism rs9344 was not associated with colorectal cancer grade (p&gt;0.05), and not associated with invasion degrees of colorectal cancer (p&gt;0.05). Taken together, we conclude that no significant association between the CCND1 gene polymorphism rs9344 with grade and invasion degree of colorectal cancer at Prof. Dr. I.G.N.G. Ngoerah Central General Hospital, Denpasar, Bali.

The value of folate receptor-positive circulating tumor cells in the diagnosis of lung cancer and its correlation with clinical characteristics.

The aim of this research is to investigate the feasibility of folate receptor-positive circulating tumor cells (FR+CTCs) as a biomarker for the diagnosis of malignant pulmonary nodules and the correlation between clinicopathological factors and FR+CTC levels. Patients initially diagnosed with one or more pulmonary nodules from a computed tomography scan were prospectively included. Three milliliters of peripheral blood was collected from each participant for FR+CTC analysis prior to surgery. Clinical and pathological parameters and FR+CTC levels were compared between patients with lung cancer and benign diseases. Six hundred fifty-three patients had lung cancer and the other 124 had benign lung diseases based on pathological examinations of the resected specimens. The median FR+CTC value of the lung cancer group was 12.0(95% CI 9.6-16.2)FU/3mL and that of the benign group was 7.2(95% CI 5.78-11.2)FU/3mL. The difference was statistically significant (P < 0.0001). In a receiver operating characteristic analysis to distinguish the two groups, the area under curve of FR+CTC was 0.7457 (95% CI 0.6893-0.8021; P < 0.0001) using a cutoff of 8.65 FU/3mL. The sensitivity was 86.37%, and the specificity was 74.19%. Combined with conventional serum tumor biomarkers, the area under curve was 0.922 (0.499-0.963). The sensitivity was 92.20%, and the specificity was 83.05%. FR+CTC levels were related to tumor staging (P4< 0.001), the degree of tumor invasion both in single (P = 0.011) and multiple lesions (P = 0.022), pathological subtypes (P = 0.013), and maximum tumor diameter (P = 0.014). FR+CTC is an effective and reliable biomarker for the diagnosis of lung cancer. Further, FR+CTC level is correlated with tumor staging, degree of invasion, pathological subtypes, and tumor size.

The comparison of Lobe-Specific or Systematic Mediastinal Lymph Node Dissection for Early-Stage Lung Adenocarcinoma With Consolidation Tumor Ratio Over 0.5

IntroductionSurgery is the most effective treatment for early-stage lung cancer. This study will propose a personalized plan for mediastinal lymph node dissection in early-stage lung adenocarcinoma to reduce the risk of surgery and improve the quality of life. MethodsThis study retrospectively analyzed the patients underwent lobectomy and lymph node dissection in the Department of Thoracic Surgery, Zhongshan Hospital, Fudan University. Clinical stage I lung adenocarcinoma patients with solid component ratio (CTR) between 0.5 and 1 were included. Patients were divided into systematic (S-MLND) and lobe-specific (L-MLND) mediastinal lymph node dissection groups. The days of hospitalization, the presence or absence of complications, the recurrence-free survival rate, and the overall survival rate were calculated to evaluate the postoperative quality and operation risk of the patients. Results210 patients (138 L-MLND and 72 S-MLND) were included. 2 lymph node metastases appeared in the S-MLND group while none in the L-MLND group (P = .049). No differences were shown in age, tumor site, size, solid component, degree of tumor invasion, and stage. The proportion of patients with severe postoperative cough and the length of hospital stay in the L-MLND group decreased. The 5-year OS of the entire cohort was 98.1%, 98.6% in L-MLND, compared with 97.2% in S-MLND; RFS was 94.8%, 95.7% in L-MLND, compared with 93.0% in S-MLND. ConclusionFor cIA lung adenocarcinoma, according to the Thin-slice CT within 1 month before the operation, if the main lesion was less than 3 cm and CTR over 0.5, L-MLND is as effective as S-MLND.

P-301 Pre-surgical carcinoembryonic antigen as a recurrence biomarker in stage III colon cancer treated with adjuvant chemotherapy in a Latin American center

Colorectal cancer represents the third most incident malignant neoplasm in the world and the second in terms of mortality. In Peru, colon cancer is positioned as the fifth malignant neoplasm in terms of incidence and the sixth, in terms of mortality(1). Surgery continues to be the curative therapy for this pathology, however, the risk of disease recurrence is still a subject of study, as well its association with risk factors, such as the degree of tumor invasion (T) and lymph node involvement (N)(2). Likewise, the role of other factors has been shown to have prognostic relevance in colon cancer patients(3,4). The main objective of this research was to determine if the preoperative carcinoembryonic antigen (CEA) level is a prognostic biomarker of recurrence and survival in patients with stage III colon cancer. A cross-sectional descriptive study was carried out, between the years 2013 and 2018, 1987 patients with colon cancer were analyzed, of which 162 patients were stage III and received adjuvant treatment with chemotherapy based on fluoropyrimidines and who complied with the inclusion criteria. The preoperative CEA level was studied (cutoff point 5); secondarily, the following clinicopathological characteristics were evaluated: age ( 45 years), albumin level ( 35 g/L), location of the primary colon (right colon vs. left colon), lymphovascular invasion (present, absent), perineural invasion (present, absent), histological grade (1, 2 or 3). The mean age was 63.7 years, 63 patients were women (38.9%), 99 patients were men (61.1%). Univariate analysis showed that the level of CEA > 5 is statistically significant (p=0.005) for recurrence. Likewise, the multivariate analysis maintained the finding of a CEA level > 5 (HR 2.71, 95%IC [1.25-5.85], p=0.011) as a prognostic factor for recurrence. Median follow-up for disease-free survival (DFS) was 31.36 months. Median DFS was not reached in either group. The DFS at 3 years in the group with CEA 5. The evaluation of the other clinicopathological characteristics were not significant. As well, it was possible to determine that the majority of recurrence cases, in the group of patients with CEA > 5, were in the first two years with a total of 18 of 21 events (85.71%). In patients with stage III colon cancer who have received adjuvant therapy, a CEA level greater than 5 has a negative impact on disease-free survival. Likewise, the greatest risk for presenting recurrence, in patients with elevated CEA, is seen in the first 2 years.

IDH-wild-type glioblastoma cell density and infiltration distribution influence on supramarginal resection and its impact on overall survival: a mathematical model.

Recent studies have proposed resection of the T2 FLAIR hyperintensity beyond the T1 contrast enhancement (supramarginal resection [SMR]) for IDH-wild-type glioblastoma (GBM) to further improve patients' overall survival (OS). GBMs have significant variability in tumor cell density, distribution, and infiltration. Advanced mathematical models based on patient-specific radiographic features have provided new insights into GBM growth kinetics on two important parameters of tumor aggressiveness: proliferation rate (ρ) and diffusion rate (D). The aim of this study was to investigate OS of patients with IDH-wild-type GBM who underwent SMR based on a mathematical model of cell distribution and infiltration profile (tumor invasiveness profile). Volumetric measurements were obtained from the selected regions of interest from pre- and postoperative MRI studies of included patients. The tumor invasiveness profile (proliferation/diffusion [ρ/D] ratio) was calculated using the following formula: ρ/D ratio = (4π/3)2/3 × (6.106/[VT21/1 - VT11/1])2, where VT2 and VT1 are the preoperative FLAIR and contrast-enhancing volumes, respectively. Patients were split into subgroups based on their tumor invasiveness profiles. In this analysis, tumors were classified as nodular, moderately diffuse, or highly diffuse. A total of 101 patients were included. Tumors were classified as nodular (n = 34), moderately diffuse (n = 34), and highly diffuse (n = 33). On multivariate analysis, increasing SMR had a significant positive correlation with OS for moderately and highly diffuse tumors (HR 0.99, 95% CI 0.98-0.99; p = 0.02; and HR 0.98, 95% CI 0.96-0.99; p = 0.04, respectively). On threshold analysis, OS benefit was seen with SMR from 10% to 29%, 10% to 59%, and 30% to 90%, for nodular, moderately diffuse, and highly diffuse, respectively. The impact of SMR on OS for patients with IDH-wild-type GBM is influenced by the degree of tumor invasiveness. The authors' results show that increasing SMR is associated with increased OS in patients with moderate and highly diffuse IDH-wild-type GBMs. When grouping SMR into 10% intervals, this benefit was seen for all tumor subgroups, although for nodular tumors, the maximum beneficial SMR percentage was considerably lower than in moderate and highly diffuse tumors.

157 Supramarginal Resection Impact on Overall Survival for IDH-Wildtype Glioblastoma According to Their Cell Density Distribution and Infiltration Profile: A Mathematical Model

INTRODUCTION: Supramarginal resection of the T2-FLAIR beyond the T1 contrast enhancement has been suggested to further improve overall survival in glioblastoma (GBM) patients, with a potentially enhanced role in IDH-wildtype. GBMs present with high variability in tumor cell density, distribution, and infiltration patterns evidenced in imaging and histological analysis. Preoperative estimation of GBM grow kinetics with advanced mathematical models can provide further insight for surgical planning. METHODS: Volumetric measurements from T1 contrast-enhancing (CE) and T2-FLAIR regions of interest from retrospective pre and postoperative MRIs of patients that underwent a gross total resection of the CE were obtained. Tumor invasiveness profile (proliferation/diffusion (ρ/D) ratio) was calculated using the following formula: where VFL and VT1 are the preoperative FLAIR and contrast-enhancing volumes, respectively. Patients were then split into nodular (ND), moderately diffuse (MD), and highly diffuse (HD) subgroups based on their tumor invasiveness profile. SMR extension and survival analyses were performed among groups. RESULTS: 101 patients met the criteria for this study. Tumors were classified as ND (n = 34), MD (n = 34), and HD (n = 33) tumors. On multivariate analysis, increasing SMR had a significant positive correlation with OS only in MD and HD tumors (HR 0.98; 95% CI, 0.98–0.99; p = 0.05, and HR 0.98; 95% CI, 0.97–0.99; p = 0.02), respectively. On threshold analysis, OS benefit was seen with SMR from 10% to 29%, 10%-59%, and 30%-90%, for ND, MD, and HD, respectively. CONCLUSION: SMR impact on overall survival in this cohort of IDH-wildtype is significantly influenced by the degree of tumor invasiveness. The results of this study showed increased overall survival with increasing SMR for moderate and highly invasive tumors. Further analysis with SMR grouped in 10% intervals demonstrated an increase in overall survival for all groups, with a lower SMR extension to benefit nodular tumors.

Interaction between peritumoral reactivity and histomorphological pattern of lymph node reactivity in oral squamous cell carcinoma: A host immune status indicator.

The invasive tumor front (ITF) of oral squamous cell carcinoma (OSCC) and the reactive changes in regional lymph nodes (RLNs) are believed to carry integral prognostic information about the tumor's invasive capacity and insight into host immune response, respectively. This study aims to evaluate the reactivity patterns of RLNs in relation to the tumor stage, grade and various histopathological parameters at the ITF of primary tumor, in an attempt to elucidate the nature of host-immune response to tumor. Pattern of invasion (POI) using Bryne's criteria, peritumoral inflammation, and status of connective tissue (CT) stroma of 50 OSCC cases, that underwent selective neck dissection were assessed at the ITF. Immunoreactivity patterns in corresponding 450 RLNs were assessed as proposed by Tsakraklides and Ioachim. Further, 97 metastatic lymph nodes (LNs) were evaluated for degree and pattern of tumor invasion. The datasets were subjected to the Chi-square analysis. There was statistically significant association (P = 0.001) of Type III and Type IV POI as well as mild peritumoral inflammation (P = 0.024) with the advanced stages of OSCC as compared to early stages. Significant association was observed between LN reactivity pattern and tumor stage (P = 0.05), with metastatic nodes exhibiting germinal center predominance (97.9%) and lymphocyte predominance (69.1%) largely observed in nonmetastatic nodes. Majority of metastatic nodes showed Grade 3 invasion (54.7%) in the form of large islands (57.7%), whereas two (2.1%) nodes were totally effaced by tumor metastasis. Statistical significance was observed between CT stroma at ITF and degree of tumor invasion in metastatic LN (P = 0.001). POI also showed significant correlation with peritumoral inflammation (P = 0.002), CT stroma (P = 0.02), and LN reactivity pattern (P = 0.03). This study supports the presence of a strong immunological host-tumor relationship.

Clinical value of tumor-associated autoantibodies in diagnosis of early non-small cell lung cancer

Objective: To investigate the auxiliary diagnostic value of seven tumor-associated autoantibodies (AABs) P53, PGP9.5, SOX2, GAGE7, GBU4-5, MAGEA1 and CAGE in early non-small cell lung cancer (NSCLC). Methods: The case-control study enrolled 195 patients with early NSCLC [71 males and 124 females, aged (55.70±11.78) years old], 114 patients with benign lung disease [44 males and 70 females, aged (52.85±12.31) years old] and 100 healthy subjects [39 males and 61 females, aged (53.62±9.97) years old] from the First Affiliate Hospital of Nanjing Medical University from June 2020 to December 2020. AABs were detected by enzyme-linked-immunosorbent serologic assay (ELISA), and carcinoembryonic antigen (CEA),cytokeratin 19-fragments (CYFRA21-1) and neuron specific enolase (NSE) were detected by electrochemiluminescence. The levels of AABs,CEA,CYFRA21-1 and NSE in the 3 groups were compared. Patients with benign lung diseases and healthy subjects were combined into the control group, and the positive rate of each indicator in the NSCLC group and the control group was compared. The diagnostic efficacy of single and combined tests for NSCLC were obtained using receiver operating characteristic (ROC) curves. Besides, the relationship between the levels of AABs, CEA, CYFRA21-1 and NSE and their clinicopathological features and preoperative imaging parameters in NSCLC patients was assessed. Results: The levels of SOX2 [0.70 (0.10, 2.40) U/mL] and GBU4-5 [1.30 (0.30, 8.90) U/mL] in NSCLC group were higher than those in benign disease group [SOX2: 0.50 (0.10, 1.60) U/mL, GBU4-5: 0.80 (0.10, 2.30) U/mL, Z values were 27.258 and 45.797; P values were all<0.05] and health control group [SOX2: 0.45 (0.10, 1.08) U/mL, GBU4-5: 0.75 (0.20, 1.78) U/mL, Z values were 32.551 and 40.456; P values were all<0.05], and there was no significant difference between benign disease group and health control group (Z values were 5.293 and 5.340, P values were all>0.05). The levels of CEA [1.75 (1.08, 2.72) U/mL] and CYFRA21-1 [1.81 (1.41, 2.36) U/mL] in NSCLC group were higher than those in healthy control group [CEA: 1.22 (0.68, 1.81) U/mL, CYFRA21-1: 1.43 (1.14, 1.74) U/mL, Z values were 64.100 and 37.597; P values were all<0.05], but there was no significant difference between NSCLC group and benign group [CEA: 1.74 (1.01, 2.51) U/mL, CYFRA21-1: 1.82 (1.45, 2.46) U/mL, Z values were 7.275 and 10.621; P values were all>0.05]. The positive rates of P53, SOX2, GAGE7, GBU4-5 and CEA in NSCLC group were higher than those in the control group [P53: 10.3% vs 0.9%, SOX2: 11.3% vs 2.3%, GAGE7: 11.3% vs 0.5%, GBU4-5: 30.1% vs 5.6%, CEA: 9.7% vs 0.9%, χ2 values were 17.420, 13.242, 22.485, 43.211, 16.255, respectively; P values were all<0.05]. The diagnostic efficiency of the combined detection of seven AABs was better than that of single detection. Seven AABs combined with CEA [area under curve (AUC): 0.732, sensitivity: 64.10%] and with CYFRA21-1 (AUC: 0.737, sensitivity: 58.97%) greatly improved the diagnostic efficiency and sensitivity of CEA (AUC: 0.583, sensitivity: 50.77%) and CYFRA21-1 (AUC: 0.552, sensitivity: 44.10%). The levels of SOX2 and CEA in NSCLC patients were correlated with the degree of tumor invasion (H values were 6.436 and 14.071; P values were all<0.05); the levels of GAGE7 and CEA were correlated with the nodule density (H values were 7.643 and 12.268; P values were all<0.05); and the levels of SOX2, GAGE7, CEA and CYFRA21-1 were all correlated with the nodule size (H values were 10.837, 11.528, 31.835, 20.338; P values were all<0.05). Conclusion: The detection of AABs combined with CEA and CYFRA21-1 is helpful for the early auxiliary diagnosis of NSCLC, and plays an important role in prevention and screening for early lung cancer.

S130 Multimodal Circulating Tumor DNA (ctDNA) Blood-Based Colorectal Cancer (CRC) Screening Test Demonstrates Clinically Meaningful Sensitivity Across Multiple Clinical Parameters

Introduction: Blood-based CRC screening holds potential to improve screening compliance due to ease of use and high patient and provider acceptability. A blood-based screening test must detect CRC across multiple clinical parameters in order to prove clinically meaningful in a screen-relevant population. We aimed to describe the performance of a multimodal ctDNA blood-based CRC screening test in a cohort of patients (pts) with newly diagnosed CRC. Methods: A consecutive, unselected series of pts with newly diagnosed CRC were consented to a study permitting use of clinical data and biospecimens for research. Consented pts provided a blood sample (10mL collected in EDTA) prior to surgical resection. Isolated plasma (median 3mL) from a cohort of pts with Stage I – III CRC was analyzed with a 500kb next-generation sequencing based panel and bioinformatic platform incorporating cell-free DNA (cfDNA) methylation-based partitioning to identify cancer related genomic alterations and epigenomic modifications (methylation and modifications in chromatin state). The output is a “ctDNA detected” or “ctDNA not detected” result. Final results were correlated with clinical features. Results: ctDNA results were available for 699 pts; 43% female, median age 63 years (range 20 - 89), 90% of pts were age 45 - 84. Overall sensitivity was 96% (671 / 699). The assay demonstrated sensitivity in the 88 – 100% range across cancer stage and presentation, primary tumor location, histology and grade, degree of tumor invasion, and microsatellite instability status (Table). Sensitivity in 138 pts with Stage I / II well-differentiated (low grade) CRC was 93%. CRC presentation status was known in 83% of pts with Stage I / II CRC (N = 344). Sensitivity was 90% in the 44% (N = 152) of pts who were asymptomatic at presentation. Sensitivity was 96% in the 56% (N = 192) of pts with Stage I / II disease who presented symptomatically. Specificity in age-matched cancer-free controls was 94%. Conclusion: This multimodal ctDNA CRC screening test has clinically meaningful sensitivity across multiple clinical parameters, most notably in those with early-stage asymptomatic disease and early-stage low-grade tumors. The data suggest this test will have clinically meaningful performance in an average risk screening population presenting with varying cancer stages and tumor histologic features. A prospective registrational study to evaluate the test in an average risk, screen-relevant cohort is ongoing (NCT04136002).Table 1.: Sensitivity of blood-based CRC screening test.

Adoption of Computed Tomography Images under Iterative Reconstruction Algorithm in Diagnosis of Gastric Cancer

Objective. This work aimed to study the application of iterative reconstruction algorithm-based computed tomography (CT) imaging in the diagnosis of gastric cancer (GC). Methods. 40 cases of GC patients diagnosed by gastroscopy biopsy and pathology in hospital were retrospectively analyzed. Scanning images of the upper abdomen were obtained after plain scanning and double-phase enhanced scanning. Then, the image was reconstructed by the iterative reconstruction algorithm, and the CT value under the algorithm was analyzed statistically. Results. It was revealed that the detection rate of both spiral CT and iterative reconstruction algorithm-based CT was 100%. After the iterative reconstruction algorithm, the image quality, image information, and image mean square error (MSE) were notably improved. The degree of tumor invasion (T) staging accuracy was 82.6%, lymph node metastasis (N) staging accuracy was 73.2%, and tumor node metastasis (TNM) staging accuracy was 79.1%. The accuracy of the iterative reconstruction algorithm-based CT was 90% for T staging, 83% for N staging, and 85.5% for TNM staging. Conclusion. Iterative reconstruction algorithm can effectively improve the spatial resolution of CT images in GC diagnosis, with high accuracy. It can provide reliable and objective imaging data for the diagnosis of GC clinically, which was worthy of further application in clinical practice.

Individualized elective irradiation of the clinically node-negative neck in definitive radiotherapy for head and neck squamous cell carcinoma.

BackgroundOral cavity (OC), oropharyngeal (OP), hypopharyngeal (HP), and laryngeal (LA) squamous cell carcinoma (SCC) have a high incidence of regional lymph node metastasis (LNM). Elective irradiation for clinically node‐negative neck is routinely administered to treat lymph nodes harboring occult metastasis. However, the optimal elective irradiation schemes are still inconclusive. In this study, we aimed to establish individualized elective irradiation schemes for the ipsilateral and contralateral node‐negative neck of these four types of cancer.MethodsFrom July 2005 to December 2018, 793 patients with OC‐SCC, 464 with OP‐SCC, 413 with HP‐SCC, and 645 with LA‐SCC were recruited retrospectively. Based on the actual incidence of LNM and the tumor characteristics, risk factors for contralateral LNM, as well as node level coverage schemes for elective irradiation, were determined using logistic regression analysis. Additionally, we developed a publicly available online tool to facilitate the widespread clinical use of these schemes.ResultsFor the ipsilateral node‐negative neck, elective irradiation at levels I‐III for OC‐SCC and levels II‐IVa for OP‐, HP‐ and LA‐SCC are generally recommended. In addition, level VIIa should be included in patients with OP‐SCC. Multivariate analyses revealed that posterior hypopharyngeal wall and post‐cricoid region involvement were independently associated with level VIIa metastasis in HP‐SCC (all P < 0.05). For the contralateral node‐negative neck, multivariate analyses revealed that ipsilateral N2b2‐N3, tumors with body midline involvement, and degree of tumor invasion were the independent factors for contralateral LNM (all P < 0.05). In patients who require contralateral neck irradiation, levels I‐II are recommended for OC‐SCC, and additional level III is recommended for patients with ipsilateral N3 disease. Levels II‐III are recommended for OP‐, HP‐, and LA‐SCC, and additional level IVa is recommended for patients with advanced T or ipsilateral N classifications. Furthermore, additional level VIIa is recommended only for OP‐SCC with T4 and ipsilateral N3 disease.ConclusionBased on our findings, we suggest that individualized and computer‐aided elective irradiation schemes could reduce irradiation volumes in OC‐, OP‐ and HP‐SCC patients, as compared to current guidelines, and could thus positively impact the patients' quality of life after radiotherapy.

Advances in radiotherapy and comprehensive treatment of high-grade glioma: immunotherapy and tumor-treating fields.

High-grade gliomas (HGGs) are the most common primary malignant brain tumors. They have a high degree of malignancy and show invasive growth. The personal treatment plan for HGG is based on the patient's age, performance status, and degree of tumor invasion. The basic treatment plan for HGG involves tumor resection, radiotherapy (RT) with concomitant temozolomide (TMZ), and adjuvant TMZ chemotherapy. The basic radiation technology includes conventional RT, three-dimensional conformal RT, intensity-modulated RT, and stereotactic RT. As our understanding of tumor pathogenesis has deepened, so-called comprehensive treatment schemes have attracted attention. These combine RT with chemotherapy, molecular targeted therapy, immunotherapy, or tumor-treating fields. These emerging treatments are expected to improve the prospects of patients with HGG. In the present article, we review the recent advances in RT and comprehensive treatment for patients with newly diagnosed and recurrent HGG.

Application of U-shaped convolutional neural network in auto segmentation and reconstruction of 3D prostate model in laparoscopic prostatectomy navigation

To investigate the efficacy of intraoperative cognitive navigation on laparoscopic radical prostatectomy using 3D prostatic models created by U-shaped convolutional neural network (U-net) and reconstructed through Medical Image Interaction Tool Kit (MITK) platform. A total of 5 000 pieces of prostate cancer magnetic resonance (MR) imaging discovery sets with manual annotations were used to train a modified U-net, and a set of clinically demand-oriented, stable and efficient full convolutional neural network algorithm was constructed. The MR images were cropped and segmented automatically by using modified U-net, and the segmentation data were automatically reconstructed using MITK platform according to our own protocols. The modeling data were output as STL format, and the prostate models were simultaneously displayed on an android tablet during the operation to help achieving cognitive navigation. Based on original U-net architecture, we established a modified U-net from a 201-case MR imaging training set. The network performance was tested and compared with human segmentations and other segmentation networks by using one certain testing data set. Auto segmentation of multi-structures (such as prostate, prostate tumors, seminal vesicles, rectus, neurovascular bundles and dorsal venous complex) were successfully achieved. Secondary automatic 3D reconstruction had been carried out through MITK platform. During the surgery, 3D models of prostatic area were simultaneously displayed on an android tablet, and the cognitive navigation was successfully achieved. Intra-operation organ visualization demonstrated the structural relationships among the key structures in great detail and the degree of tumor invasion was visualized directly. The modified U-net was able to achieve automatic segmentations of important structures of prostate area. Secondary 3D model reconstruction and demonstration could provide intraoperative visualization of vital structures of prostate area, which could help achieve cognitive fusion navigation for surgeons. The application of these techniques could finally reduce positive surgical margin rates, and may improve the efficacy and oncological outcomes of laparoscopic prostatectomy.

Cord Blood-Derived Stem Cells Suppress Fibrosis and May Prevent Malignant Progression in Recessive Dystrophic Epidermolysis Bullosa.

Recessive dystrophic epidermolysis bullosa (RDEB) is a severe skin fragility disorder caused by mutations in the Col7a1 gene. Patients with RDEB suffer from recurrent erosions in skin and mucous membranes and have a high risk for developing cutaneous squamous cell carcinoma (cSCCs). TGFβ signaling has been associated with fibrosis and malignancy in RDEB. In this study, the activation of TGFβ signaling was demonstrated in col7a1-/- mice as early as a week after birth starting in the interdigital folds of the paws, accompanied by increased deposition of collagen fibrils and elevated dermal expression of matrix metalloproteinase (MMP)-9 and MMP-13. Furthermore, human cord blood-derived unrestricted somatic stem cells (USSCs) that we previously demonstrated to significantly improve wound healing and prolong the survival of col7a1-/- mice showed the ability to suppress TGFβ signaling and MMP-9 and MMP-13 expression meanwhile upregulating anti-fibrotic TGFβ3 and decorin. In parallel, we cocultured USSCs in a transwell with RDEB patient-derived fibroblasts, keratinocytes, and cSCC, respectively. The patient-derived cells were constitutively active for STAT, but not TGFβ signaling. Moreover, the levels of MMP-9 and MMP-13 were significantly elevated in the patient derived-keratinocytes and cSCCs. Although USSC coculture did not inhibit STAT signaling, it significantly suppressed the secretion of MMP-9 and MMP-13, and interferon (IFN)-γ from RDEB patient-derived cells. Since epithelial expression of these MMPs is a biomarker of malignant transformation and correlates with the degree of tumor invasion, these results suggest a potential role for USSCs in mitigating epithelial malignancy, in addition to their anti-inflammatory and anti-fibrotic functions. Stem Cells 2018;36:1839-12.

Relationship between expression of PIK3CA protein and the clinicopathology of esophageal squamous cancer

Objective To analyze the expression and clinical significance of PIK3CA protein in squamous cell carcinoma of the esophagus. Methods Forty-five samples of surgical resection of esophageal squamous cell carcinoma were collected as the observation group, and 45 normal tissues adjacent to the carcinoma were selected as the control group.The expression of PIK3CA protein in the tissues of esophageal squamous cell carcinoma and the corresponding para cancerous tissue was detected by immunohistochemistry (IHC). Results The results of IHC showed that the positive expression rate of PIK3CA protein in esophageal squamous cell carcinoma was 53.33%, which in adjacent normal tissues was 0.00%, the difference was statistically significant (χ2=32.727, P<0.01). The positive expression rate of PIK3CA protein was correlated with lymph node metastasis, differentiation and clinical stage of esophageal squamous cell carcinoma (χ2=5.180, 8.201, 13.566, P=0.023, 0.017, 0.001), and was not correlated with the degree of tumor invasion(χ2=0.952, P=0.329). Conclusion The expression of PIK3CA protein is abnormal in esophageal squamous cell carcinoma, and the expression of PIK3CA protein plays a role in the occurrence and development of esophageal squamous cell carcinoma. Key words: Esophageal neoplasms; Phosphatidylinositol 3-kinase; Pathology, clinical

Surgical Decision Making From Image-Based Biophysical Modeling of Glioblastoma: Not Ready for Primetime.

Biophysical modeling of glioma is gaining more interest for clinical practice. The most popular model describes aggressivity of tumor cells by two parameters: net proliferation rate (ρ) and propensity to migrate (D). The ratio ρ/D, which can be estimated from a single preoperative magnetic resonance imaging (MRI), characterizes tumor invasiveness profile (high ρ/D: nodular; low ρ/D: diffuse). A recent study reported, from a large series of glioblastoma multiforme (GBM) patients, that gross total resection (GTR) would improve survival only in patients with nodular tumors. To replicate these results, that is to verify that benefit of GTR would be only observed for nodular tumors. Between 2005 and 2012, we considered 234 GBM patients with pre- and postoperative MRI. Stereotactic biopsy (BST) was performed in 109 patients. Extent of resection was assessed on postoperative MRI and classified as GTR or partial resection (PR). Invasiveness ρ/D was estimated from the preoperative tumor volumes on T1-Gadolinium-enhanced and fluid-attenuated inversion recovery sequences. We demonstrate that patients with diffuse GBM (low ρ/D), as well as more nodular (mid and high ρ/D) GBM, presented significant survival benefit from GTR over PR/BST ( P < .001). Whatever the degree of tumor invasiveness, as estimated from MRI-driven biophysical modeling, GTR improves survival of GBM patients, compared to PR or BST. This conflicting result should motivate further studies.

Analysis of survival rates and prognostic factors among patients with oral squamous cell carcinoma

Aim: The aim of the study was to estimate global and accumulated survival rates as well as prognostic factors among patients with oral squamous cell carcinoma (OSCC). Subject and methods: Data from the previous 5 years were extracted from patient charts at a cancer reference center. The occurrence of death resulting from the malignant tumor in patients with a diagnosis of OSCC was the dependent variable. The independent variables were tumor site, degree of cell differentiation, clinical staging, data of histopathological determination of OSCC, socio-demographic characteristics, smoking habit and treatment modality. Kaplan-Meier survival curves were created. Differences were analyzed using the log-rank and Wilcoxon tests. The Cox regression model was employed to evaluate factors associated with survival, with the calculation of hazard ratios (HR) (α = 5%). Results: The global survival rate was 57%. The stage of the tumor exercised a direct influence on accumulated survival. In the first year of evaluation, the survival rate of patients in stages I and II was 92.6%. The Cox regression analysis revealed the following variables to be significantly associated with survival: T classification of the clinical staging (HR = 2.283; 95% CI: 1.115–4.673) and degree of tumor invasion (HR = 1.834; 95% CI: 1.041–3.232). Conclusion: Clinical stage and degree of tumor invasion are important prognostic factors for OSCC.

Endoscopic endonasal pituitary adenomas surgery: the surgical experience of 178 consecutive patients and learning curve of two neurosurgeons.

BackgroundWe aim to study surgical technique and analyze the related factors affecting tumor total removal and postoperative endocrinological remission for endoscopic endonasal pituitary adenomas surgery.MethodsWe retrospectively analyzed 178 endoscopic endonasal pituitary adenomas surgery from March 2011 to May 2014. Endonasal approach included the routine transnasal-sphenoidal approach, transnasal- maxillary sinus approach in four cases and transnasal-clivus approach in one case.ResultsAccording to postoperative imaging data and endocrine examination results, total removal was achieved in 129 patients (72.5%), and endocrinological remission was achieved in 38 patients with functional adenomas (44.1%). Statistical analysis of the clinical data showed that total removal rate was much closely related to tumor volume (P = 0.006), and tumor invasiveness (P < 0.001).ConclusionsIn this study, we found tumor sizes and invasion of cavernous sinus were related to total removal rate and endocrinological remission rate; the direction and degree of tumor invasion, and the surgeon’s experience were the key influence factors of the endocrinological remission rate for invasive functional pituitary adenomas.

Prognostic significance of nestin in primary malignant melanoma of the oral cavity.

Several studies have examined the correlation between nestin expression and the degree of tumor invasion in cutaneous melanoma. However, no information has been reported on nestin in primary mucosal melanoma of the head and neck. The present study examined the expression and prognostic significance of nestin in patients with primary mucosal melanoma of the oral cavity. Nestin expression was examined immunohistochemically in 39 patients (six oral melanoma in-situ cases and 33 invasive oral melanoma cases) and analyzed for association with disease progression. Age, sex, anatomic site, stage, level of invasion, regional lymph node metastasis, surgical margin involvement, and treatment modality were also analyzed. In the 33 invasive melanoma cases, invasion depth correlated significantly with prognosis in univariate and multivariate analyses. High-intensity nestin staining was observed in 14 of the 33 cases and a high proportion of nestin-positive cells was observed in 16 cases. In stage III oral melanoma cases, nestin expression was not significantly associated with disease progression. However, in stage IV cases, both the intensity and the proportion of nestin expression were significantly associated with disease progression (P=0.022 and 0.005, respectively). In all 33 invasive cases, multivariate analyses showed that both the intensity and the proportion of nestin were significantly associated with a poor prognosis (P=0.014 and 0.009; hazard ratio, 3.59 and 4.05; 95% confidence interval, 1.29-9.98 and 1.42-11.56, respectively). In conclusion, nestin can be a valuable prognostic indicator in the advanced-stage (stage IV) cases of oral mucosal melanoma.