Negative Node Metastasis Research Articles

Significance of CD133 Expression in Invasive Ductal Carcinoma of the Breast

Background and Aim: Cancer stem cells (CSCs) are thought to be responsible for tumor initiation, progression, and resistance to chemotherapy and radiotherapy. CD133 is a trans-membrane glycoprotein which is considered as a putative CSCs marker. Emerging evidence suggests that CD133 may be a critical factor in tumor development, progression and metastasis. The aim of this study was to evaluate the expression of CD133 in mammary infiltrating ductal carcinoma (IDC), and to correlate its expression with some known clinicopathological parameters. Methods: Fifty patients with mammary IDC who underwent modified radical mastectomy were included in this study. From each specimen, two tissue sections were obtained; one was stained by hematoxylin and eosin (H&E) stain to determine the histologic subtype, grade and indicators of local aggressiveness. The second tissue section was immunohistochemically stained by anti-human CD133 antibody. Results: The study revealed statistically significant associations between CD133 expression and poorly differentiated, advanced stage tumors with poor Nottingham Prognostic Index (NPI), triple negative phenotype, lymphovascular invasion (LVI) and lymph node metastasis (LNM). Conclusion: The current study revealed that CD133 is strongly associated with poor prognostic indices; it is positively correlated to poorly-differentiated tumors with high histologic grade and advanced stage

Characterization of E-cadherin expression in normal mucosa, dysplasia and adenocarcinoma of gastric cardia and its influence on prognosis.

BACKGROUNDGastric cardia adenocarcinoma (GCA), which has been classified as type II adenocarcinoma of the esophagogastric junction in western countries, is of similar geographic distribution with esophageal squamous cell carcinoma in China, and even referred as "sister cancer" by Chinese oncologists. The molecular mechanism for GCA is largely unknown. Recent studies have shown that decreased expression of E-cadherin is associated with the invasion and metastasis of multiple cancers. However, the E-cadherin expression has not been well characterized in gastric cardia carcinogenesis and its effect on GCA prognosis.AIMTo characterize E-cadherin expression in normal gastric cardia mucosa, dysplasia and GCA tissues, and its influence on prognosis for GCA.METHODSA total of 4561 patients with GCA were enrolled from our previously established GCA and esophageal cancer databases. The enrollment criteria included radical surgery for GCA, but without any radio- or chemo-therapy before operation. The GCA tissue from 4561 patients and matched adjacent normal epithelial tissue (n = 208) and dysplasia lesions (n = 156) were collected, and processed as tissue microarray for immunohistochemistry. The clinicopathological characteristics were retrieved from the medical records in hospital and follow-up was carried out through letter, telephone or home interview. E-cadherin protein expression was determined by two step immunohistochemistry. Kaplan–Meier and Cox regression analyses were used to correlate E-cadherin protein expression with survival of GCA patients.RESULTSOf the 4561 GCA patients, there were 3607 males with a mean age of 61.6 ± 8.8 and 954 females with a mean age of 61.9 ± 8.6 years, respectively. With the lesions progressed from normal gastric cardia mucosa to dysplasia and GCA, the positive immunostaining rates for E-cadherin decreased significantly from 100% to 93.0% and 84.1%, respectively (R2 = 0.9948). Furthermore, E-cadherin positive immunostaining rate was significantly higher in patients at early stage (0 and I) than in those at late stage (II and III) (92.7% vs 83.7%, P = 0.001). E-cadherin positive expression rate was significantly associated with degree of differentiation (P = 0.001) and invasion depth (P < 0.001). Multivariate analysis showed that the GCA patients with positive E-cadherin immunostaining had better survival than those with negative (P = 0.026). It was noteworthy that E-cadherin positive expression rate was similar in patients with positive and negative lymph node metastasis. However, in patients with negative lymph node metastasis, those with positive expression of E-cadherin had better survival than those with negative expression (P = 0.036). Similarly, in patients with late stage GCA, those with positive expression of E-cadherin had better survival than those with negative expression (P = 0.011). CONCLUSIONE-cadherin expression may be involved in gastric cardia carcinogenesis and low expression of E-cadherin may be a promising early biomarker and overall survival predictor for GCA.

Machine learning revealed molecular classification of colorectal cancer with negative lymph node metastasis

Purpose: Accurate preoperative staging directly affects the treatment decision of patients with rectal cancer. However, our understanding of the immune subclasses of CRC without lymph node metastasis is still incomplete. Materials and methods: Here, we first analyzed the subclasses of CRC without lymph node metastasis on the Cancer Genome Atlas (TCGA) and verified its stability in the GSE39582 dataset. Four immune subclasses (C1–C4) were identified and verified by non-negative matrix factorization (NMF) of gene expression profiles. Then, ICI scores of six genes were constructed to characterize subclasses. Results: There were significant differences in metabolic and progression-associated signatures, immune characteristics, and clinical characteristics among subclasses. C3 represented a good prognosis with high TMB. C4 showed unique immune characteristics. We believe that C3 is the initial stage of CRC. After the C1 and C2 stages, it progresses to the C4 stage, and finally, lymph node metastasis occurs. Conclusions: This work may help to provide a basis for immunotherapy decision-making in early CRC and may guide personalized methods of cancer immunotherapy.

Higher Lymph Node Metastasis Rate and Poorer Prognosis of Intestinal-Type Gastric Cancer Compared to Diffuse-Type Gastric Cancer in Early-Onset Early-Stage Gastric Cancer: A Retrospective Study

Background: The incidence of early-onset gastric cancer (GC) that was diagnosed at <50 years is increasing, but there is a knowledge gap on early-onset early-stage GC (EEGC) that was defined as early-onset GC limited to the mucosa or submucosa. Therefore, we comprehensively analysed the clinical features based on Lauren type.Methods: Logistic and Cox analyses were used to investigate risk factors for lymph node metastasis (LNM) and prognosis, respectively. Propensity score matching (PSM) was used to adjust confounding factors. Protein mass spectrometry analysis was used to explore the molecular mechanism of LNM.Result: Our study included 581 patients with EEGC from the Surveillance, Epidemiology, and End Results (SEER) database and 226 patients with EEGC from our own centre. We identified intestinal type, T1b stage, and tumour size (>3 cm) as risk factors for LNM using SEER and our own data. We also found that the prognosis of patients with intestinal-type EEGC was poorer than patients with diffuse-type EEGC, and T1b stage and positive LNM were hazard factors for survival. After analysing the expression of proteins between positive and negative LNM in the intestinal or diffuse type, we found no similar proteins between these groups. The differentially expressed genes (DEGs) in the intestinal type functioned as epithelial cell signalling in Helicobacter pylori. The DEGs in the diffuse type functioned in the tricarboxylic acid cycle (TCA cycle) and oxidative phosphorylation.Conclusion: For EEGC, our study was the first report to demonstrate that the intestinal type was a risk factor for LNM and survival compared to the diffuse type, and the oncogenic expression promoting the occurrence of LNM was different. These findings suggest that clinicians should pay more attention to intestinal-type EEGC than diffuse-type EEGC.

Metabolic Activity of Visceral Adipose Tissue Is Associated with Metastatic Status of Lymph Nodes in Endometrial Cancer: A 18F-FDG PET/CT Study.

Obesity contributes to increased cancer incidence and aggressiveness in patients with endometrial cancer. Inflamed metabolic activity of visceral adipose tissue (VAT) is regarded as a key underlying mechanism of adverse consequences of obesity. The aim of this study was to investigate the association between inflammatory metabolic activity of VAT evaluated by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and metastatic status of lymph nodes (LN) in patients with endometrial cancer. In total, 161 women with newly diagnosed endometrial cancer, who received preoperative 18F-FDG PET/CT, were enrolled. VAT inflammatory metabolic activity was defined as V/S ratio and measured from the maximum standardized uptake value (SUVmax) of VAT normalized to the SUVmax of subcutaneous adipose tissue (SAT). The positive LN metastasis group exhibited a significantly higher V/S ratio than the negative LN metastasis group. Systemic inflammatory surrogate markers including high sensitivity C-reactive protein, spleen SUVmax, and bone marrow SUVmax were also higher in the LN metastasis group than in the negative LN metastasis group, showing significant correlations with V/S ratio. In multivariate logistic regression analysis, V/S ratio was independently associated with LN metastasis. V/S ratio is independently associated with the LN metastasis status in patients with endometrial cancer. This finding could be useful as a potential surrogate marker of obesity-induced VAT inflammation associated with tumor aggressiveness.

The association between polymorphism of the long noncoding RNA, Plasmacytoma variant translocation 1, and the risk of gastric cancer.

Genetic polymorphisms of plasmacytoma variant translocation 1 can affect various tumors including gastro-intestinal, sexual hormone sensitive cancers and lymphoma. Accumulated evidence have shown that plasmacytoma variant translocation 1 acts as an oncogene and tumor suppressor in various cancers. In fact, the rs13255292 and rs2608053 single nucleotide polymorphisms of plasmacytoma variant translocation 1are known to affect lymphoma; however, their effects on gastric cancer are primarily unknown. In this study, we evaluated the association between these plasmacytoma variant translocation 1 polymorphisms and the risk of gastric cancer.In the present study, 462 patients diagnosed with gastric cancer and 377 cancer-free controls were enrolled. The TaqMan genotyping assay was used to analyze the association between rs13255292 and rs2608053 single nucleotide polymorphisms and the risk of gastric cancer.The rs2608053 dominant model (CT + TT) was associated with a decreased risk of gastric cancer in T3 + T4 (odds ratio [OR] = 0.61, confidence interval (CI) = 0.41 – 0.92, P = .019), and stage III Gastric cancer subgroups (OR = 0.59, 95% CI = 0.38 – 0.91, P = .017) compared to the CC genotype. When stratified analysis by sex was carried out, the rs13255292 dominant model (CT + TT) had a significant association with an increased risk of gastric cancer in the female negative lymph node metastasis gastric cancer subgroup, compared to the CC genotype (OR = 1.96, 95% CI = 1.16 – 3.30, P = .012). The recessive model (TT) of rs13255292 was associated with an increased risk of gastric cancer in the male T3 + T4 gastric cancer subgroups compared to the CC + CT genotype (OR = 3.82, 95% CI = 1.02 – 14.33, P = .047). The dominant model (CT + TT) of rs2608053 was related to a decreased risk of gastric cancer in male T3 + T4 (OR = 0.57, 95% CI = 0.33 – 0.98, P = .042) and stage III gastric cancer subgroups (OR = 0.49, 95% CI = 0.27 – 0.89, P = .020) compared to the CC genotype.The rs13255292 and rs2608053 single nucleotide polymorphisms in plasmacytoma variant translocation 1 may contribute to susceptibility of gastric cancer. Further studies with more subjects and different ethnic groups are needed to validate our results.

Establishment of a multi-parameters MRI model for predicting small lymph nodes metastases (

PurposeTo evaluate the potential role of MR findings and DWI parameters in predicting small regional lymph nodes metastases (with short-axis diameter < 10 mm) in pancreatic ductal adenocarcinomas (PDACs).MethodsA total of 127 patients, 82 in training group and 45 in testing group, with histopathologically diagnosed PDACs who underwent pancreatectomy were retrospectively analyzed. PDACs were divided into two groups of positive and negative lymph node metastases (LNM) based on the pathological results. Pancreatic cancer characteristics, short axis of largest lymph node, and DWI parameters of PDACs were evaluated.ResultsUnivariate and multivariate analyses showed that extrapancreatic distance of tumor invasion, short-axis diameter of the largest lymph node, and mean diffusivity of tumor were independently associated with small LNM in patients with PDACs. The combining MRI diagnostic model yielded AUCs of 0.836 and 0.873, and accuracies of 81.7% and 80% in the training and testing groups. The AUC of the MRI model for predicting LNM was higher than that of subjective MRI diagnosis in the training group (rater 1, P = 0.01; rater 2, 0.008) and in a testing group (rater 1, P = 0.036; rater 2, 0.024). Comparing the subjective diagnosis, the error rate of the MRI model was decreased. The defined LNM-positive group by the MRI model showed significantly inferior overall survival compared to the negative group (P = 0.006).ConclusionsThe MRI model showed excellent performance for individualized and noninvasive prediction of small regional LNM in PDACs. It may be used to identify PDACs with small LNM and contribute to determining an appropriate treatment strategy for PDACs.

Nomogram to Predict the Occurrence and Prognosis of Distant Metastasis in T1N0 Colon Cancer: A SEER Data-Based Study.

PurposeDistant metastasis (DM) is relatively rare in T1 colon cancer (CC) patients, especially in those with negative lymph node metastasis. The aim of this study was to explore the main clinical factors and build nomogram for predicting the occurrence and prognosis of DM in T1N0 colon cancer patients.MethodsPatients with T1N0 stage CC were collected from the Surveillance, Epidemiology, and End Result (SEER) database. All patients were divided into development and validation cohorts with the 3:1 ratio. Logistic regressions were performed to analyze the clinical risk factors for DM. Cox regression model was used to identify potential prognostic factors for patients with DM. The performance of nomogram was evaluated by concordance index (C-index), calibration curves, receiver operating characteristic (ROC) curves and decision curve analyses (DCAs). Based on cancer-specific survival (CSS), Kaplan–Meier curves were generated and analyzed using Log rank tests.ResultsA total of 6770 patients were enrolled in this study, including 428 patients (6.3%) with DM. Age, size, grade, CEA were independent risk factors associated with DM. Age, grade, CEA, surgery and chemotherapy were independent prognostic factors for CSS. Nomograms were applied and C-index, calibration curves, ROC curves and DCA curves proved good discrimination, calibration and clinical practicability of the nomogram in predicting the occurrence and prognosis of DM in T1N0 CC patients. In the DM nomogram, the AUCs for development and validation cohort were 0.901 (95% CI = 0.879–0.922) and 0.899 (95% CI=0.865–0.940), respectively. The calibration curves (development cohort: S: p = 0.712; validation cohort: S: p = 0.681) showed the relatively satisfactory prediction accuracy. Similarly, the AUCs of the nomogram at 1-, 2-, and 3-year were 0.763 (95% CI=0.744–0.782), 0.794 (95% CI=0.775–0.813), and 0.822 (95% CI=0.803–0.841) for the development cohort, and 0.785 (95% CI=0.754–0.816), 0.748 (95% CI=0.717–0.779) and 0.896 (95% CI=0.865–0.927) for the validation cohort in the CSS nomogram. The C-indices of the development and validation cohort were 0.718 (95% CI=0.639–0.737) and 0.712 (95% CI=0.681–0.743).ConclusionThe population-based nomogram could help clinicians predict the occurrence and prognosis of DM in T1N0 CC patients and provide a reference to perform appropriate metastatic screening plans and rational therapeutic options for the special population.

Prediction of lateral lymph node metastasis using OSNA method for mesorectal lymph nodes in low rectal cancer: A prospective study by the Kanagawa Yokohama Colorectal Cancer Study Group (KYCC1801).

Contrary to the Japanese guidelines recommendations regarding lateral lymph node dissection (LatLND) for rectal cancer, its omission is common in clinical practice without reliable omission criteria. Negative pathological mesorectal lymph node metastasis (MesLNM) is reportedly highly correlated with negative pathological lateral lymph node metastasis (p-LatLNM); however, this cannot be used as a criterion because pathological features are revealed postoperatively. Herein, we prospectively evaluated the negative predictive value (NPV) of MesLNM diagnosed via the one-step nucleic acid amplification (OSNA) method for p-LatLNM. This prospective study was conducted at a single academic study group in Japan. The key eligibility criterion was mid-to-low rectal cancer planned to be treated using mesorectal excision with LatLND. According to the study protocol, the OSNA method was considered useful if the point estimate of the NPV exceeded 95%. Preoperative case registration was conducted between 2018 and 2020; 34 patients were registered. Among these, 16 were negative for OSNA-MesLNM, and negative p-LatLNM was confirmed in all cases. The point estimate of the NPV was 100%, with the 95% confidence interval ranging from 79.4% to 100.0%. The OSNA method is useful in selecting patients in whom LatLND can be omitted in real-world clinical practice.

A Specific Predicting Model for Screening Skip Metastasis From Patients With Negative Central Lymph Nodes Metastasis in Papillary Thyroid Cancer.

Skip metastasis is a specific type of papillary thyroid cancer lymph node metastasis (LNM). The present study aimed to clarify the typical clinical characteristics of skip metastasis and optimize the prediction model, so as to provide a more individual treatment mode for skip metastasis. We retrospectively analyzed 1075 PTC patients with different lymph node metastasis statuses from two clinical centers. Comparisons have been made between patients with skip metastasis and other types of LNM. Univariate and multivariate analyses were performed to detect the risk factors for skip metastasis with negative LNM, and a nomogram for predicting skip metastasis was established. The rate of skip metastasis was 3.4% (37/1075). Compared with other types of LNM, significant differences showed in tumor size, upper portion location, thyroid capsular invasion, and ipsilateral nodular goiter with the central lymph node metastasis (CLNM) group, and in age and gender with the lateral lymph node metastasis (LLNM) group. Four variables were found to be significantly associated with skip metastasis and were used to construct the model: thyroid capsular invasion, multifocality, tumor size > 1 cm, and upper portion. The nomogram had good discrimination with a concordance index of 0.886 (95% confidence interval [CI], 0.823 to 0.948). In conclusion, the significant differences between skip metastasis and other types of LNM indicated that the lymph node drainage pathway of skip metastasis is different from either CLNM or LLNM. Furthermore, we established a nomogram for predicting risk of skip metastasis, which was able to effectively predict the potential risk of skip metastasis in patients without preoperative LNM clue.

Clinicopathological and computed tomographic features associated with occult lymph node metastasis in patients with peripheral solid non-small cell lung cancer

ObjectivesTo investigate the value of combining clinicopathological characteristics with computed tomographic (CT) features of tumours for predicting occult lymph node metastasis (OLNM) in peripheral solid non-small cell lung cancer (PS-NSCLC). MethodsThe study included 478 NSCLC clinically N0 (cN0) patients who underwent lobectomy and systemic lymph node dissection from January 2014 to August 2019. Patients were classified into OLNM and negative lymph node metastasis (NLNM) groups. The CT features of non-metastatic and metastatic lymph nodes with a largest short-diameter > 5 mm were compared in the OLNM group. Thereafter, the clinicopathological characteristics and CT morphological features of tumours were compared between both groups. Multivariable logistic regression analysis and receiver-operating characteristic curve were developed. ResultsCT images detected 103 metastatic and 705 non-metastatic lymph nodes, and no significant differences in CT features of lymph nodes were found in all 161 OLNM patients (P > 0.05). For both groups, sex, carcinoembryonic antigen and pathological type differed significantly (all P < 0.05), while tumour size, necrosis, calcification, vascular convergence, pleural involvement, and the shortest interval of tumour-pleura differed significantly on CT images (all P < 0.05). Multivariable logistic regression analysis showed that carcinoembryonic antigen > 5.00 ng/ml, adenocarcinoma, absence of vascular convergence, and pleural involvement of Type II (one linear or cord-like pleural tag or tumour abut to the pleura with a broad base observed on both lung and mediastinal window images) were independent predicting factors of OLNM. ConclusionsCT findings of lymph nodes can provide limited value and integrating clinicopathological characteristics with the CT morphological features of tumours is helpful in predicting OLNM in patients with PS-NSCLC.

Tumor-derived exosomes drive immunosuppressive macrophages in a pre-metastatic niche through glycolytic dominant metabolic reprogramming

One of the defining characteristics of a pre-metastatic niche, a fundamental requirement for primary tumor metastasis, is infiltration of immunosuppressive macrophages. How these macrophages acquire their phenotype remains largely unexplored. Here, we demonstrate that tumor-derived exosomes (TDEs) polarize macrophages toward an immunosuppressive phenotype characterized by increased PD-L1 expression through NF-kB-dependent, glycolytic-dominant metabolic reprogramming. TDE signaling through TLR2 and NF-κB leads to increased glucose uptake. TDEs also stimulate elevated NOS2, which inhibits mitochondrial oxidative phosphorylation resulting in increased conversion of pyruvate to lactate. Lactate feeds back on NF-κB, further increasing PD-L1. Analysis of metastasis-negative lymph nodes of non-small-cell lung cancer patients revealed that macrophage PD-L1 positively correlates with levels of GLUT-1 and vesicle release gene YKT6 from primary tumors. Collectively, our study provides a novel mechanism by which macrophages within a pre-metastatic niche acquire their immunosuppressive phenotype and identifies an important link among exosomes, metabolism, and metastasis.

Using Computed Tomography Lymphography for Mapping of Sentinel Lymph Nodes in Patients with Breast Cancer.

Objectives:In breast cancer surgery, the combined use of the dye method and radioisotope (RI) method is recommended for identifying sentinel lymph nodes. However, the RI method is difficult to license, expensive, and difficult to introduce. Thus, we introduced computed tomography lymphography (CTLG) and investigated the characteristics and usefulness of CTLG.Material and Methods:Among breast cancer patients who underwent surgery during a 6-year period from January 2013 to December 2018, CTLG was performed on 141 patients with clinically negative lymph node metastasis. These cases were then retrospectively investigated. The number and location of lymph vessel, true sentinel lymph nodes, and the positional relationships with surrounding muscles and blood vessels were confirmed from the constructed 3D images. The actual surgeries were then performed using a dye method with indigo carmine based on images obtained using CTLG.Results:CTLG was able to identify lymph vessels and true sentinel lymph nodes in 131 of the 141 cases (92.91%). There were 97 patients in whom the first true sentinel lymph node reached from the breast was one node, 30 with two nodes, and 4 with three nodes. Moreover, there were three cases in which sentinel lymph nodes were present at Level II. During surgery, sentinel lymph nodes were identified in 131 patients (92.91%) using dye.Conclusion:CTLG has a high identification rate in sentinel lymph nodes, and it is considered a convenient and useful examination method because a lot of information, such as the number and position of sentinel lymph nodes, can be obtained.

Correlation of primary tumor metabolic parameters with clinical, histopathological and molecular characteristics in breast cancer patients at pre-operative staging FDG-PET/CT study

BackgroundThe aim of this prospective study was to evaluate the correlation of primary tumor metabolic activity parameters; maximum standardized uptake value (SUVmax) and tumor SUVmax/liver average SUV ratio (TLR) with clinical, histopathological and molecular characteristics of initial staging breast cancer (BC) patients using 18F-fluorodeoxyglucose (FDG) positron emission tomography / computerized tomography (PET/CT) scan.ResultsForty female patients with newly diagnosed BC were enrolled in our study, age ranging from 31-78 years (mean 50.5 +/- SD11.7).All the primary tumors were detected with mean SUVmax 10.8(+/-SD 7.9). The mean /median SUVmax values of primary tumor was higher in premenopausal , stage III and IV, Estrogen Receptors negative( ER-), Progesterone Receptors negative(PR-), Human epidermal growth factor receptor 2 positive ( Her2neu+) patients, high nuclear grade (GIII), triple negative molecular subgroup (TN) and positive axillary lymph node (ALNs) metastasis,(P= 0.003, 0.017, 0.113, 0.089 0.01 ,0.002 , 0.007 and 0.016 respectively).The mean/median TLR values was higher in premenopausal ,Her2neu+, GIII, TN molecular subtype patients, stage III and IV and in patients with positive ALNs , ER- and PR - patients (P= 0.002, 0.0476 , 0.005 , 0.018 , 0.039 and 0.022, 0.095 and 0.129 respectively).SUVmax of the primary lesion and TLR were moderately negatively correlated with the age of the patients (P= 0.005 and 0.008 respectively), also they were moderately positively correlated with the size of the primary tumor (P= 0.019 and 0.036 respectively). TLR was predictive of nodal involvement AUC= 0.612 (95% CI: 0.431-792). The overall sensitivity and specificity of PET/CT for axillary staging was 100 % and 60 %, respectively (P= 0.006).ConclusionThe SUVmax of the primary tumor and TLR values had similar significant associations with different prognostic factors in BC but only TLR can predict nodal involvement.

Breast ductal carcinoma in situ with micro-invasion versus ductal carcinoma in situ: a comparative analysis of clinicopathological and mammographic findings

To determine the differences in clinicopathological and mammographic findings between ductal carcinoma in situ (DCIS) and ductal carcinoma in situ with micro-invasion (DCIS-MI) and explore clinicopathological and mammographic factors associated with DCIS-MI. All DCIS patients with or without micro-invasion who underwent preoperative mammography at The Affiliated Hospital of Qingdao University from January 2016 through June 2020 were identified retrospectively. The correlations of clinicopathological findings with DCIS-MI were evaluated using univariate and multivariate binary logistic regression analyses. Imaging findings were compared between the groups by using the Pearson chi-square test. A total of 445 DCIS lesions and 151 DCIS-MI lesions were included in the final analysis. Large extent (≥2.7 cm), high nuclear grade, comedo-type, negative progesterone receptor (PR), negative oestrogen receptor (ER), high Ki-67 and axillary lymph node metastasis were more frequently found in DCIS-MI than in DCIS (all p<0.05), and the first four of these were found to be independent predictors of DCIS-MI in the multivariate analysis (all p<0.05). Regarding imaging findings, compared to DCIS, DCIS-MI showed fewer occult lesions and more lesions with calcifications in mass, asymmetry, and architectural distortion (p=0.004). Grouped calcifications were usually associated with DCIS, while regional calcifications were commonly found in DCIS-MI (p<0.05). Large extent, high nuclear grade, comedo-type and negative PR were found to be independent predictors of DCIS-MI. Lesions with calcifications and regional calcifications were more likely associated with DCIS-MI on mammography.

Is prophylactic lateral lymph node dissection needed for lower rectal cancer? A single-center retrospective study

BackgroundThe effectiveness of prophylactic lateral lymph node dissection (LLND) in treating patients with lower rectal cancer remains controversial and has not been clearly established. Therefore, we aimed to retrospectively analyze the survival impact of prophylactic LLND in patients with lower rectal cancer.MethodsData of 301 patients with lower rectal cancer (tumor’s lower edge on the anal side of the peritoneal reflexion) with clinical T3 disease and negative preoperative lateral lymph node metastasis, who underwent radical resection (R0) at our hospital between April 2007 and March 2017, were included in this study. Patients who received preoperative chemotherapy or radiotherapy were excluded. The relapse-free survival (RFS) and overall survival (OS) rates were compared between the dissection (prophylactic LLND, n = 37) and non-dissection (no prophylactic LLND, n = 264) groups.ResultsSignificantly fewer men and younger patients were noted in the dissection group than in the non-dissection group. Post-surgery 3- and 5-year RFS rates were 69.6% and 66.8% in the dissection group and 75.1% and 72.5% in the non-dissection group, respectively (5-year post-surgery RFS, p = 0.58). In the dissection and non-dissection groups, the 5-year OS rates were 86.5% and 79.7%, respectively (p = 0.29), and the 5-year cancer-specific survival rates were 88.9% and 86.0%, respectively (p = 0.29), with no significant differences. Lateral lymph node recurrence was observed in one (2.7%) and 10 patients (3.8%) in the dissection and non-dissection groups, respectively, and there was no significant difference between the groups.ConclusionsIn this study, the effectiveness of prophylactic LLND was limited in patients with > T3 lower rectal cancer with no evidence of preoperative lymph node metastasis. Prophylactic LLND may not be necessary if there is no preoperative lymph node metastasis, even if the invasion depth is T3 or higher.

Valor clínico de los parámetros metabólicos de la PET en el carcinoma vulvar primario

PurposeWe aim to establish the prognostic value of metabolic parameters of the primary tumor in patients diagnosed with vulvar squamous cell carcinoma (VSCC) who underwent a pretreatment 18F FDG PET/CT scan. Materials and methodsThis retrospective study included 47 patients with a histopathologically confirmed diagnosis of VSCC, and who underwent a 18F FDG PET/CT scan prior to treatment. The disease stage and age at diagnosis, the maximum standardized uptake value (SUVmax), SUVmean, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) values of the primary tumor, based on a baseline PET scan, were recorded. The relationship between these factors, and progression-free survival (PFS) and overall survival (OS) was evaluated. ResultsThe mean age of the 47 study patients was 69.6±1.9 years. Among the patients, 18 were in early stage of the disease and 29 were in the advanced stage. The age, and SUVmax, SUVmean, MTV and TLG values were statistically significantly associated with OS and PFS. Furthermore, it was noted that OS and PFS were significantly longer in the early stage patients than in the advanced stage patients, in patients with a tumor size <4cm than those with a tumor size ≥4cm, and in patients with a negative lymph node metastasis than those with a positive lymph node metastasis. ConclusionOur findings suggest that PET parameters are prognostic factors for VSCC. To the best of our knowledge, this study is the first to investigate the prognostic value of the PET parameters of primary tumors in patients with VSCC, and as such, we believe it contributes to literature.

The Prognostic Significance of c-Met and p53 Immunohistochemical Expression in Gastric and Colorectal Carcinomas

BACKGROUND: Colorectal and gastric carcinomas are the most common and deadly gastrointestinal (GIT) malignancies. AIM: This study aimed to evaluate the expression of c-Met and p53 in gastric and colorectal carcinomas (CRCs) as well as colorectal adenomas using immunohistochemistry. MATERIALS AND METHODS: c-Met and p53 immunohistochemical expression was conducted on 66 cases of gastric adenocarcinomas and total of 60 colonic cases (36 CRCs and 24 colorectal adenomas). RESULTS: In this study, c-Met was positively expressed in 54.5% of gastric carcinomas and 50% of CRCs. In addition, p53 was positively expressed in 56.1% of gastric carcinomas and 72.2% of CRCs. Moreover, higher expression of both c-Met (p = 0.001) and p53 expression (p &lt; 0.001) was reported in CRCs compared to colorectal adenomas. In the same context, c-Met and p53 expressions were positively correlated with intestinal type gastric adenocarcinoma (p &lt; 0.001 and p = 0.03, respectively). Moreover, c-Met was correlated with non-mucinous adenocarcinomas (p = 0.008) and lower grades (p &lt; 0.001) of gastric carcinomas. As regard survival analysis in gastric carcinomas, median overall survival (OS) was better in p53 positive patients (p = 0.05), patients with negative lymph node metastasis (p = 0.03), and patients with better response to neoadjuvant chemotherapy (p = 0.04). In contrast, c-Met did not exhibit significant correlation with OS (p &gt; 0.05). Both c-Met and p53 did not reveal significant correlation with tumor stage and site in both CRCs and gastric carcinomas (p &gt; 0.05). CONCLUSION: We concluded that c-Met and p53 are expressed in the most common GIT malignancies addressing them as potential biomarkers. In addition, c- Met and p53 may have a potential role in colorectal cancer development as they showed higher positivity in CRCs compared to adenomas.

Prognostic Value of Lymph Node Dissection for Intrahepatic Cholangiocarcinoma Patients With Clinically Negative Lymph Node Metastasis: A Multi-Center Study From China.

BackgroundThe clinical value of lymph-node dissection (LND) for intrahepatic carcinoma (ICC) patients with clinically negative lymph node metastasis (LNM) remains unclear; hence we conducted a multi-center study to explore it.MethodsPatients who were diagnosed ICC with clinically negative LNM and underwent hepatectomy with or without LND from December 2012 to December 2015 were retrospectively collected from 12 hepatobiliary centers in China. Overall survival (OS) was analyzed using the Kaplan–Meier method, and then subgroup analysis was conducted stratified by variables related to the prognosis.ResultsA total of 380 patients were eligible including 106 (27.9%) in the LND group and 274 (72.1%) in the non-LND group. Median OS in the LND group was slightly longer than that in the non-LND group (24.0 vs. 18.0 months, P = 0.30), but a significant difference was observed between the two groups (24.0 vs. 14.0 months, P = 0.02) after a well-designed 1:1 propensity score matching without increased severe complications. And, LND was identified to be one of the independent risk factors of OS (HR = 0.66, 95%CI = 0.46–0.95, P = 0.025). Subgroup analysis in the matched cohort showed that patients could benefit more from LND if they were male, age <60 years, had no HBV infection, with ECOG score <2, CEA ≤5 ug/L, blood loss ≤400 ml, transfusion, major hepatectomy, resection margin ≥1 cm, tumor size >5 cm, single tumor, mass-forming, no satellite, no MVI, and no perineural invasion (all P < 0.05). Furthermore, only patients with pathologically confirmed positive LNM were found to benefit from postoperative adjuvant therapy (P < 0.001).ConclusionWith the current data, we concluded that LND would benefit the selected ICC patients with clinically negative LNM and might guide the postoperative management.

Predicting pathological lymph node status in clinical stage IA peripheral lung adenocarcinoma.

Even with current diagnostic technology, it is difficult to accurately predict pathological lymph node status (PLNS). This study aimed to develop a prediction model of PLNS in peripheral adenocarcinoma with a dominant solid component, based on clinical and radiological factors on thin-section computed tomography, to identify patients to whom wedge resection or other local therapies could be applied. Of 811 patients enrolled in a prospective multi-institutional study (JCOG0201), 420 patients with clinical stage IA peripheral lung adenocarcinoma having a dominant solid component were included. Multivariable logistic regression was performed to develop a model based on clinical and centrally reviewed radiological factors. Leave-one-out cross-validation and external validation analyses were performed, using independent data from 221 patients. Sensitivity, specificity and concordance statistics were calculated to evaluate diagnostic performance. The formula for calculating the probability of pathological lymph node metastasis included the following variables: tumour diameter (including ground-glass opacity), consolidation-to-tumour ratio and density of solid component. The concordance statistic was 0.8041. When the cut-off value associated with the risk of incorrectly predicting negative pathological lymph node metastasis (pN-) was 4.9%, diagnostic sensitivity and specificity in predicting PLNS were 95.7% and 46.0%, respectively. The concordance statistic for the external validation set was 0.7972, and diagnostic sensitivity and specificity in predicting PLNS were 95.4% and 40.5%, respectively. The proposed model is clinically useful and successfully predicts pN- in patients with clinical stage IA peripheral lung adenocarcinoma with a dominant solid component.