Depth Of Primary Tumor Invasion Research Articles

FDG PET/CT and Endoscopic Ultrasound for Preoperative T-Staging of Esophageal Squamous Cell Carcinoma.

This study aimed to compare the diagnostic performances of endoscopic ultrasound (EUS) and FDG PET/CT in the preoperative T-staging of esophageal squamous cell carcinoma (ESCC) and determine whether their innovative coordination achieves better prediction. In total, 100 patients diagnosed with ESCC, 57 without (CRT[-]sub) and 43 with (CRT[+]sub) neoadjuvant chemoradiotherapy, undergoing EUS and FDG PET/CT, followed by surgical resection of the tumor, were included in this analysis. EUS classified T-stages based on the depth of primary tumor invasion, and FDG PET/CT used thresholded maximal standardized uptake value (SUVmax) classifications. By employing pathology results as the reference standard, we assessed the accuracy of EUS and FDG PET/CT, evaluated their concordance using the κ statistic, and conducted a comparative analysis between the two modalities through McNemar's chi-square test. FDG PET/CT had higher overall accuracy than EUS (for CRT[-]sub: 71.9%, κ = 0.56 vs. 56.1%, κ = 0.31, p = 0.06; for CRT[+]sub: 65.1%, κ = 0.50 vs. 18.6%, κ = 0.05, p < 0.01) in predicting pT- and ypT-stage. Our proposed method of incorporating both FDG PET/CT and EUS information could achieve higher accuracies in differentiating between early and locally advanced disease in the CRT[-]sub group (82.5%) and determining residual viable tumor in the CRT[+]sub group (83.7%) than FDG PET/CT or EUS alone. FDG PET/CT had a better diagnostic ability than EUS to predict the (y)pT-stage of ESCC. Our complementary method, which combines the advantages of both imaging modalities, can deliver higher accuracy for clinical applications of ESCC.

Vascular Endothelial Growth Factor and Soluble Forms of Its Receptors 1 and 2 in Gastric Cancer.

Comparative evaluation of blood content of VEGF, sVEGFR1, and sVEGFR2 in 104 primary gastric cancer patients and 65 healthy persons was performed and associations of these markers with the principal clinical and morphological characteristics of gastric cancer were analyzed. The median levels of VEGF and sVEGFR1 in gastric cancer patients significantly surpassed the control: by 1.5 (p<0.001) and 1.2 times (p<0.01), respectively. On the contrary, sVEGFR2 level in patients was below the control (p<0.001). The best sensitivity-specificity ratio (64 and 65%, respectively) was observed for VEGF at 347 pg/ml cut-off value, which is insufficient for the use of this parameter as a clinically valuable serological marker for gastric cancer. No significant associations of these markers with the disease stage, depth of primary tumor invasion, its histological type, grade, or localization were found. The serum level of VEGF in patients with metastases to more than 7 regional lymph nodes (N3) was significantly higher than in patients without lymph node metastases (N0). Blood content of sVEGFR1 in patients with distant metastases (М+) was lower than in patients without distant metastases (М0). Thus, VEGF and its receptors circulating in the peripheral blood do not play significant diagnostic role in gastric cancer, but could be useful in monitoring and prognosis of the efficiency of antiangiogenic therapy.

Determinants of Survival for Patients with Neoadjuvant-Treated Node-Negative Gastric Cancer.

This study sought to determine prognostic markers for disease recurrence and survival in a cohort of neoadjuvant-treated, node-negative gastric cancer patients (ypT0-4N0M0). Clinicopathologic data from patients treated with neoadjuvant therapy followed by curative-intent gastrectomy at the University of Texas MD Anderson Cancer Center from 1995 to 2017 were evaluated. Patients with AJCC TNM stage ypT0-4N0M0 were considered for analysis. The inclusion criteria were met by 212 patients with a mean age of 58.3 years. Of these patients, 60 % were male, 53 % were Caucasian, 87 % received chemoradiation, and 13 % received chemotherapy. The findings showed a median overall survival (OS) rate of 11.3 years, a 5-year survival rate of 72 %, and a 10-year survival rate of 57 %. During a median follow-up period of 5.5 years, 38.2 % of the patients died. In the multivariable analysis, ypT4-stage and nodal yield fewer than 16 were significantly associated with reduced OS. Cancer classified as ypT4 had more aggressive biologic traits, including lymphovascular and perineural invasion, and was treated more aggressively with total gastrectomy and additional organ resection despite frequent positive margins. Depth of invasion remained significantly associated with worse outcome after the analysis controlled for nodal yield and possible stage migration. Compared with ypT0-3 tumors, ypT4 cancers were associated with significantly more recurrences (13 % vs. 45 %; p < 0.05), and the primary modes of failure for ypT4 lesions were local recurrence and peritoneal metastases (88 % of recurrences). Depth of primary tumor invasion and nodal yield were significantly associated with OS among the patients with ypT0-4N0M0 gastric cancer. Serosal invasion (ypT4) was associated with a high rate of peritoneal recurrence, and trials of intraperitoneal therapy targeting these patients should be considered.

Фактор роста эндотелия сосудов и растворимые формы его рецепторов 1-го и 2-го типов при раке желудка

Comparative evaluation of blood content of VEGF, sVEGFR1, and sVEGFR2 in 104 primary gastric cancer patients and 65 healthy persons was performed and associations of these markers with the principal clinical and morphological characteristics of gastric cancer were analyzed. The median levels of VEGF and sVEGFR1 in gastric cancer patients significantly surpassed the control: by 1.5 (p<0.001) and 1.2 times (p<0.01), respectively. On the contrary, sVEGFR2 level in patients was below the control (p<0.001). The best sensitivity-specificity ratio (64 and 65%, respectively) was observed for VEGF at 347 pg/ml cut-off value, which is insufficient for the use of this parameter as a clinically valuable serological marker for gastric cancer. No significant associations of these markers with the disease stage, depth of primary tumor invasion, its histological type, grade, or localization were found. The serum level of VEGF in patients with metastases to more than 7 regional lymph nodes (N3) was significantly higher than in patients without lymph node metastases (N0). Blood content of sVEGFR1 in patients with distant metastases (М+) was lower than in patients without distant metastases (М0). Thus, VEGF and its receptors circulating in the peripheral blood do not play significant diagnostic role in gastric cancer, but could be useful in monitoring and prognosis of the efficiency of antiangiogenic therapy.

Validation and Evaluation of Diagnostic Efficiency of Genes Associated with Colorectal Cancer with Hyperglycemia

Objective To verify the expressions of genes associated with colorectal cancer with hyperglycemia and evaluate their diagnostic values.Methods Tumor tissues,distal normal intestinal mucosa,and peripheral blood samples were harvested from 109 colorectal cancer patients and peripheral blood samples from 30 diabetes patients and 30 healthy volunteers. The mRNA expressions of glucose regulated protein 78 (GRP78),NADPH oxidase-1 (NOX1),carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5),heat shock protein 60 (HSP60),and histone deacetylase 1(HDAC1) were detected by real-time quantitative polymerase chain reaction. The correlation between the gene expressions and clinicopathological parameters in colorectal cancer patients were analyzed using Pearson's correlation analysis. Diagnostic test accuracy evaluation was used to calculate the sensitivity,specificity,accuracy,predictability,Youden index,and likelihood ratio of serum gene expressions in colorectal cancer patients,and the receiver operating characteristic (ROC) curves were drawn. The area under the ROC curve was calculated to evaluate the diagnostic efficiency of the combined detection of multiple genes.Results The mRNA levels of GRP78 (P=0.001),NOX1 (P=0.022),CEACAM5 (P=0.000),HSP60 (P=0.044),and HDAC1 (P=0.047) were positively correlated with the fasting blood glucose level. The mRNA expressions of NOX1 (P=0.000,P=0.008) and HDAC1 (P=0.000,P=0.037) in tissues and serum were significantly higher in colorectal cancer patients than in patients with normal blood glucose levels. The NOX1 mRNA expression was positively correlated with the diameter of colorectal cancer (P=0.013),and the HDAC1 mRNA expression was significantly correlated with the tumor site (P=0.049),depth of primary tumor invasion (P=0.025),and TNM stage (P=0.042). The areas under the ROC curves of NOX1,CEACAM5,and HDAC1 were 0.931,0.852,and 0.860 respectively (all P=0.000). The specificity,accuracy,and negative predictive value of NOX1,HDAC1 mRNA expression in colorectal cancer patients with hyperglycemia were all above 90%. The diagnostic sensitivity and specificity of the combined detection of NOX1,CEACAM5,and HDAC1 were 98.82% and 99.93%,respectively.Conclusion Combined detection of genes associated with colorectal cancer accompanied by hyperglycemia can improve the diagnostic efficiency of early screening.

Prognostic significance of metastatic lymph node ratio in squamous cell carcinoma of the cervix.

PurposeMetastatic lymph node ratio (MLNR) was reported to be an important prognostic factor in several tumors. However, depth of primary tumor invasion is also important in cervical cancer prognostic analysis. In this study, the objective was to determine if MLNR can be used to define a high-risk category of patients with squamous cell carcinoma of the cervix (SCC). And we combined MLNR and depth of invasion to investigate whether prognosis of SCC can be predicted better.Patients and methodsWe performed a retrospective review of patients with SCC who underwent radical hysterectomy and pelvic lymphadenectomy at QiLu Hospital of Shandong University from January 2007 to December 2009. Prognostic factors for disease-free survival (DFS) and overall survival (OS) were identified by univariate and multivariate analyses.ResultsOne hundred and ninety-eight patients met the inclusion criteria and were included in the analysis. By cut-point survival analysis, MLNR cutoff was designed as 0.2. On multivariate analysis, an MLNR >0.2 was associated with a worse OS (hazard ratio [HR] =2.560, 95% CI 1.275–5.143, P=0.008) and DFS (HR =2.404, 95% CI 1.202–4.809, P=0.013). Depth of invasion cutoff was designed as invasion >1/2 cervix wall and was associated with a worse OS (HR =1.806, 95% CI 1.063–3.070, P=0.029) and DFS (HR =1.900, 95% CI 1.101–3.279, P=0.021). In addition, subgroup analysis revealed significant difference in OS and DFS rates between different MLNR categories within the same depth of invasion category (P<0.05), however, not between different depth of invasion categories within the same MLNR category (P>0.05).ConclusionMLNR may be used as the independent prognostic parameter in patients with SCC. Combined MLNR and depth of invasion can predict both OS and DFS better in SCC than one factor. Besides, MLNR appears to be a better prognostic value than depth of invasion for SCC.

Adenylyl Cyclase-Associated Protein 1 in the Development of Head and Neck Squamous Cell Carcinomas.

We compared the content of adenylyl cyclase-associated protein 1 (CAP1) in the blood and tissues of patients with head and neck squamous cell carcinomas (with and without regional metastases), patients with chronic inflammatory diseases aggravated by laryngeal and laryngopharyngeal dysplasia, and healthy individuals. The data suggest that serum CAP1 concentration correlated with the depth of primary tumor invasion and the presence of regional metastases. In cancer patients, the serum level of CAP1 was lower than in patients with laryngeal and laryngopharyngeal dysplasia, which can be of importance for differential and timely diagnostics of malignant tumors.

Single Nucleotide Polymorphism of the Enhancer of Zeste Homolog 2 Gene rs2072408 is Associated with Lymph Node Metastasis and Depth of Primary Tumor Invasion in Gastric Cancer.

The single nucleotide polymorphism (SNP) rs2072408 is located in an intron of the enhancer of zeste homolog 2 (EZH2) gene. Its role in gastric cancer (GC) has not been determined. In the present study, the genotype of (EZH2) rs2072408 and the relationship of genotype with lymph node metastasis (LNM) and the invasive depth of gastric wall (T stage) was determined in 330 patients with GC, and the association between the genotype and recurrence and survival was determined in 253 patients with GC. The TT genotype was identified to be significantly associated with LNM [P = 0.013; odds ratio (OR), 6.49 (95% confidence interval (CI), 1.47 - 28.59)] and T stage [T1 + T2 vs. T3 + T4, p = 0.017, OR, 3.02 (95% CI, 1.22 - 7.44)]. The overall rates of LNM and T3 + T4 stage in the present study were 70.6% and 60.6%, respectively, the rates increased 23.8% and 20.0% in patients with the TT genotype. These results suggest that the TT genotype of EZH2 (rs2072408) was associated with LNM and the depth of gastric wall invasion in patients with GC.

Prognostic significance of metastatic lymph nodes ratio in patients with gastric adenocarcinoma after curative gastrectomy

Background We evaluated the impact of the number of metastatic lymph nodes and the metastatic lymph nodes ratio (the ratio between metastatic lymph nodes and total dissected lymph nodes, MLNR) in patients with gastric adenocarcinoma following curative gastrectomy and also analyzed the relationship between the number of removed lymph nodes and prognosis in node-negative gastric cancer. Methods From January 2005 to December 2010, 1 390 patients who were diagnosed with gastric adenocarcinoma and underwent curative gastrectomy were included. In particular, lymph node metastasis was not present in 515 patients. The number of metastatic lymph nodes and the metastatic lymph nodes ratio were selected for univariate and multivariate analyses to evaluate their influences on the disease outcome. The survival curve was presented according to the number of removed lymph nodes in node-negative gastric cancer using Kaplan-Meier plots. Results The overall 5-year survival rate was 54% in this group. Univariate analysis revealed that age category, macroscopic appearance, histological grade, tumor size, depth of primary tumor invasion, number of metastatic lymph nodes, metastatic lymph nodes ratio, tumor, nodes, metastasis-classification (TNM) stage and status of lymphovascular, and vessel invasion have significant impact on survival. The number of metastatic lymph nodes and the metastatic lymph nodes ratio both have significant impact on survival (P &lt;0.001). However, in multivariate analyses, only the metastatic lymph nodes ratio was identified to be an independent prognostic factor (P &lt;0.001). The number of removed lymph nodes in node-negative was a strong prognostic factor of survival, the more lymph nodes dissected, the better the survival. Conclusions The metastatic lymph nodes ratio has more significant prognostic value for survival in patients with gastric cancer following curative gastrectomy than the number of metastatic lymph nodes. The number of removed lymph nodes might be an important prognostic factor for gastric cancer without lymph node metastasis.

Factors influencing the risk of recurrence in patients with esophageal carcinoma treated with surgery: A single institution analysis consisting of 1002 cases

The aim of this study was to identify the risk of recurrence in patients with thoracic esophageal squamous cell carcinoma (TESCC) treated with curative surgery. The retrospective analysis included 1002 consecutive patients with TESCC who had been treated with curative surgery in Zhejiang Cancer Hospital, China, between 2003 and 2008. Univariate and multivariate analyses using the Kaplan-Meier method and Cox proportional hazards model, respectively, were performed to identify the independent risk factors for locoregional recurrence and all the recurrence events. The 2-and 5-year recurrence rates were 39.0 and 59.2%, respectively. More than 85% of recurrences occurred within 36 months. The variables associated with a higher rate of recurrence in the univariate analysis were gender (male), length of tumor (≥5 cm), depth of invasion (deeper), lymph node metastasis (greater), histological grade (higher) and vessel involvement (positive). By multivariate analyses, gender (HR, 1.7; 95% CI, 1.2-2.5; P=0.002), depth of invasion (HR, 1.4; 95% CI, 1.2-1.6; P<0.001) and lymph node involvement (HR, 1.4; 95% CI, 1.3-1.5; P<0.001) were independent predictive factors of recurrence. Post-operative radiotherapy or chemotherapy did not significantly prolong failure-free survival (FFS), particularly in patients with early-stage disease. Information regarding the depth of primary tumor invasion and the number of lymph nodes involved may help in evaluating the recurrence risk in patients with TESCC treated with curative surgery. Further studies are required to clarify the correlation between recurrence and the different multidisciplinary treatment approaches.

A Curative Resection Improves the Postoperative Survival Rate Even in Patients with Advanced Gallbladder Carcinoma

The aim of this study was to evaluate the results of our series of 90 operations for gallbladder carcinoma according to the Japanese Society of Biliary Surgery (JSBS) classification system and to clarify the appropriate surgical strategy for advanced gallbladder carcinoma based on the depth of primary tumor invasion and lymph node metastasis. Generally, only a surgical resection can achieve a prognostic improvement of the advanced gallbladder carcinoma. The survival of patients with this neoplasm depends strictly on the depth of histological primary tumor invasion and lymph node metastasis. A retrospective analysis was conducted on 90 patients from 1990 to 2004 who underwent a surgical resection of gallbladder carcinoma. The factors influencing survival were examined. Thirty-nine patients with palliative treatment (not resected cases), which was diagnosed as T3 or T4 by preoperative imagings, were also included in this study. The significance of the variables for survival was examined by the Kaplan–Meier method and the log-rank test followed by multivariate analyses using Cox’s proportional hazard model. Portal invasion, lymph node metastasis, the surgical margin (+ vs. −) and the final curability (fCurA, B vs. C) were all found to be independent prognostic factors in the multivariate analysis. In pT2 gallbladder carcinoma, a better survival was achieved in an aggressive surgical approach, in order of a S4a+S5 hepatic resection, an extended cholecystectomy and a cholecystectomy. In pT3 and pT4, although radical extended surgery did not provide the opportunity for good survival even after lobectomy of the liver, the survival of patients with curative surgery was statistically better than in those without curative surgery. In addition, the nodal involvement of pN1 to pN2 was better than that with pN3. A S4a+S5 hepatectomy, therefore, appears to be adequate for the treatment of pT2 gallbladder carcinoma. Even in patients with pT3 and pT4 gallbladder carcinoma, long-term survival can be expected by an operation with a tumor-free surgical margin. The role of radical surgery, however, is considered to be limited in patients with pN3 lymph node metastasis.

Building Upon the Standard of Care in Adjuvant Therapy of High-Risk Melanoma

Melanoma is the fifth most frequent cancer among males and the sixth most frequent cancer in females. It takes a toll in productive life years that is exceeded only by childhood cancers and testicular carcinoma. Melanoma incidence has increased consistently during the past two generations. However, the depth of primary tumor invasion—the cardinal prognostic factor of localized primary melanoma—has decreased. As a consequence, the case fatality rate has decreased from 50% to less than 10% during the past 50 years. Despite these advances, 8,000 deaths in the United States each year are attributable to melanoma. The death rate has increased 157% in the past decade among older men, a subset of the population who present with thicker lesions ( 4.0 mm) that may have evaded detection or may represent a biologically different process. Against this background, it is daunting that no therapy has ever shown a significant prolongation of survival in large, properly conducted, randomized clinical trials for metastatic disease. Only one, interferon alfa-2b (IFN -2b), has shown a significant benefit in terms of overall and relapse-free survival in multicenter randomized United States cooperative group and intergroup trials. These facts suggest that we have much to do in both patient and physician education and in development of better therapies for melanoma. Richtig et al report in this issue of the Journal of Clinical Oncology the closure of the European Cooperative Adjuvant Melanoma Treatment Study Group (ECAMTSG) placebocontrolled trial of isotretinoin and low-dose IFN compared with low-dose IFN in patients with resected stage IIA and IIB melanoma. Unfortunately, like many other recent trials of adjuvant therapy for melanoma, this trial was closed and reported early when an interim analysis demonstrated no significant likelihood of reaching the initial study goals (1.3%). With this negative experience, and a series of other negative trials recently reported in the literature or in abstracts, it is time to ask the question, How may progress be accelerated and the pitfalls of past trials avoided in future melanoma studies? The potential answers to this complex question may be found in our increasing understanding of the requirements of adjuvant clinical trial design and our scientific understanding of tumor progression, along with an analysis of current effective therapies. Only one adjuvant therapy has stood the test of time: the high-dose IFN -2b regimen tested initially in the Eastern Cooperative Oncology Group E1684 trial and reassessed in the United States intergroup E1690 and E1694 trials reported in the Journal of Clinical Oncology in 1996, 2000, and 2001. These trials have taught us many things, including the importance of prognostic factors for melanoma outcome and the necessity of concurrently randomized controlled trials for rigorous assessment of new interventions. They also point to the large time window between new trial initiation and the return of meaningful answers regarding disease-free and overall survival. The evolution of prognostic factors between trial cohorts, even when trial entry criteria have been relatively consistent in the United States cooperative groups, argues for standardization of major prognostic variables as far as is possible to optimize detection of differences related to experimental interventions. Trials conducted in the recent past have taught us that only robust trials that include sufficient numbers of patients to have the power to arrive at unequivocal conclusions are worthy of our patients’ involvement. The design of clinical trials depends on the anticipated rate of relapse and mortality for the population to be treated: the lower the risk of the group selected, the larger the number of patients needed to answer the trial question. Events among patients with resected stage IIIB to IV disease exceed those for stage IIIA and those, in turn, exceed those for stage IIB and IIA. The numbers required for trials designed to detect clinically relevant differences for survival and progression-free interval increase from 600 to 800 for stage IIIB to IV to numbers that may exceed 1,400 for stage IIIA and stage IIA/B disease. The ECAMSTG study JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 23 NUMBER 34 DECEMBER 1 2005

舌癌Ｔ１・Ｔ２症例の再発因子 臨床病理学的検討

Significant factors related to primary recurrence of T1/T2 carcinoma of the tongue and neck lymph node metastasis were analyzed with the use of logistic analysis in 108 patients. All patients had undergone Cot laser resection between March 1980 and April 1997. The factors analyzed included: (1) primary site of the carcinoma, (2) differentiation of squamous cell carcinomas, (3) diameter of the primary tumor, (4) absence/presence of perineural invasion of the primary tumor, (5) absence/presence of intravascular invasion of the primary tumor, (6) absence/presence of in-tramuscular invasion of the primary tumor, (7) depth of primary tumor invasion. (8) surgical margin of the resected primary tumor, and (9) absence/presence of irradiation. Significant risk factors for primary recurrence were a surgical margin of less than 4 mm and tumor coverage of the posterior third of the mobile tongue. A significant risk factor in neck lymph node metastasis was depth of primary tumor invasion of more than 4 mm, no other significant factors for the primary recurrence or regional recurrence were observed. The results suggested that a deep surgical margin of more than 10 mm was nesessary, and that if the primary lesion occupied the posterior third of the mobile tongue, an extended surgical resection was nesessary. In addition, if the depth of the primary tumor invasion is more than 4 mm, preventive modified radical neck dissection is recommended.

Prognostic value of DNA index, S‐phase fraction and p53 protein accumulation after surgical resection of esophageal squamous‐cell carcinomas in Thailand

The prognostic value of cell nuclear DNA content, S-phase fraction and p53 protein accumulation in esophageal squamous-cell carcinomas was studied in a consecutive series of 80 patients from a high-incidence region of southern Thailand, who underwent esophagectomy between 1983 and 1993. Flow cytometry was used to determine tumor ploidy, DNA index and S-phase fraction, while p53 protein accumulation was evaluated immunohistochemically using the monoclonal anti-p53 antibody, CO7. Biomarkers were correlated with clinico-pathologic findings and survival by univariate and multivariate analysis. p53 protein was found in 40 tumors (50%), and was associated with significantly reduced overall survival. In patients with immunopositive tumors, depth of primary tumor invasion, lymph-node status. TNM stage and tumor grade were also significant prognostic factors. Additional predictors of reduced overall survival after esophagectomy, determined by flow cytometry, included S-phase fraction above 10%, aneuploidy (DNA index 1.2-1.8) and multiploidy (DNA index > 2.2). This study further implicates p53 in the pathogenesis of esophageal squamous-cell carcinoma. Prognostic factors such as p53 protein, S-phase fraction and DNA index may be useful in stratifying patients for adjuvant therapies in future clinical trials of esophageal cancer.

Endoscopic ultrasonography in the diagnosis, staging and follow-up of esophageal and gastric cancer.

The accumulating data show that endoscopic ultrasonography (EUS) is highly compatible with the UICC/AJCC staging classification for esophageal and gastric cancer, based on the TNM system expressing anatomical extent of disease. The great strength of EUS in staging these cancers is its ability to image the gut wall and adjacent structures in unique detail. EUS is more accurate than computed tomography in staging the depth of primary tumor invasion (T) and regional lymph node metastases (N). High frequency EUS is not useful in staging for distant metastases (M) due to limited depth of the field. EUS also has limitations in reliably distinguishing between neoplastic and inflammatory tissue. Thus, the major use of EUS is in staging rather than in diagnosis. However, initial reports indicate that EUS may be helpful in the detection of malignancy in Barrett's esophagus, in diagnosing post-operative recurrent cancer, and in evaluating the response to non-operative therapy. EUS appears to represent an important advance in the staging and follow-up of patients with esophageal and gastric cancer. Instruments and techniques will continue to evolve, but the next level of research should be designed to show that the improved staging provided by EUS has clinical utility and can affect patient outcome.