Evaluation of Serum Amyloid A as a Biomarker for Gastric Cancer

Background Serum amyloid A (SAA) is a useful biomarker for gastric cancer in an animal model. We investigated the potential of SAA as a biomarker for gastric cancer in humans. Methods Serum levels of SAA from 96 gastric cancer patients were measured before and after curative gastrectomy; 32 patients with gastric ulcers and 52 healthy subjects were the control groups. The immunohistochemical study was performed to evaluate the protein expression over gastric cancer tissue slides. Results The mean SAA concentration was higher in gastric cancer patients (88.54 ± 50.44 mg/l) than in healthy subjects (3.36 ± 2.29 mg/l) and gastric ulcer patients (10.48 ± 8.97 mg/l) (P < .05). The SAA concentration was associated with tumor stage (P = .0244) and location (P = .0016) but not with Lauren’s histological type (P = .839). In the multivariate analysis, SAA level was correlated with tumor location (P < .0001) and lymph node status (P < .05). During follow-up, the mean SAA concentration increased significantly in 24 patients with tumor recurrence (P < .05) but did not change in 77 patients without recurrence. In the survival analysis, patients with SAA levels > 97 mg/l had a nearly fourfold increase in risk of death. Immunoreactivity was most prominent in blood vessel regions but not within cancer cells. Conclusions These data not only demonstrated SAA was useful in predicting survival of patients with gastric cancer, but they also showed that SAA was a valuable tool for postoperative follow-up.     

Serum Neopterin as a Prognostic Indicator in Patients with Gastric Carcinoma

ABSTRACT?

Purpose: To evaluate the possible association between serum neopterin level and clinical and laboratory findings and their prognostic value of patients with gastric carcinoma. Methods: Serum samples were collected from patients (n = 38) and normal volunteers (n = 39) and stored at –80°C until analyzed. Neopterin, C-reactive protein (CRP), and IL-6 concentration were measured by ELISA. The clinicopathological parameters were determined by reviewing both medical charts and pathological records. Results: Mean neopterin levels were 15.26 ± 11.46 nmol/L in patients with gastric carcinoma and 9.87 ± 2.90 nmol/L in the control group. Serum neopterin concentrations were significantly higher in patients with gastric carcinoma than in the control group. The number of patients with elevated neopterin level was significantly correlated with stage, gastric wall involvement, the number of metastatic lymph nodes, and the level of serum CRP. The mean neopterin concentrations were significantly elevated in patients older than 60 years, in the presence of venous invasion and increased metastatic lymph node number, and in patients with elevated CRP levels. Neopterin level was also correlated with overall survival as an independent prognostic indoicator. Conclusions: Serum neopterin levels were elevated in patients with advanced gastric cancer and correlated with prognostic parameters and overall survival. Moreover, neopterin measured at the time of diagnosis can be used to predict the survival of gastric carcinoma.     

抑癌基因Runt相关转录因子3在胃癌中的表达及其与临床病理学因素的关系

目的探讨胃癌组织中Runt相关转录因子3（Runx3）基因的表达情况及其与胃癌临床病理学因素的关系。方法采用逆转录聚合酶链反应（RT—PCR）和蛋白印迹（Western blot）法分别检测52例胃癌组织和配对的正常胃黏膜组织中Runx3 mRNA以及蛋白的表达水平，并分析Runx3表达与胃癌临床病理学因素的关系。结果59．6％（31／52）的胃癌组织出现Runx3 mRNA表达缺失，48．1％（25／52）出现Runx3蛋白表达缺失，其缺失率均明显高于对应的正常胃黏膜组织（P〈0．05）。Runx3的表达缺失与肿瘤大小、组织分化程度、浸润深度、淋巴结转移及TNM分期有关（P〈0．05，P〈0．01）。Runx3 mRNA表达与蛋白表达呈正相关（r=0．840，P〈0．01）。结论Runx3基因与胃癌的发生、发展密切相关，有望成为胃癌诊断和治疗的新靶点。     

The Significance of Perineural Invasion as a Prognostic Factor in Patients with Gastric Carcinoma

Purpose: Few studies have investigated the prognostic significance of perineural invasion (PNI) in gastric cancer. Therefore, we examined the association between PNI and clinicopathological factors and the effect of PNI on overall survival in patients with gastric carcinoma. Methods: Paraffin sections of surgical specimens from 354 patients who underwent gastric resection were stained with hematoxylin and eosin. PNI was assessed histologically as positive when cancer cells were seen in the perineurium or neural fascicles. Survival analysis was done in 219 patients with T_2,3,4 tumors who underwent potentially curative resection. Data were collected prospectively. Results: PNI was positive in 211 of the 354 patients (59.6%). The ratio of undifferentiated tumors, tumors with vascular invasion, and lymph node metastasis was significantly higher in the PNI-positive patients than in the PNI-negative patients (P < 0.0001 for all three associations). As the depth of mural invasion increased, so did PNI positivity (P < 0.0001). The overall survival of the PNI-positive patients was significantly worse than that of the PNI-negative patients in the univariate analysis (P = 0.0009). However, PNI had no independent prognostic significance in the multivariate Cox proportional hazards model analysis. When the patients were separated into subgroups, PNI had prognostic value in patients with T₃ tumors (P = 0.036) and no lymph node metastasis (P = 0.005) in the univariate analysis, but no prognostic significance in the multivariate analysis. Conclusions: Although the incidence of PNI is high in gastric carcinoma and increases with the progression of disease, it does not provide any additional information to the classical prognostic parameters. Received: March 4, 2002 / Accepted: July 2, 2002 Reprint requests to: N. Duraker, Ata-2 Sitesi Manolya Cad., ?am Sokak B-5 9-A Da:10, ?engelk?y 81210, Istanbul, Turkey     

新型超声刀在胃癌根治术中的应用及技巧

目的探讨新型超声刀在胃癌根治术中使用的效果及技巧。方法回顾性分析四川大学华西医院2007年1月至2008年5月期间使用新型超声刀进行胃癌根治术的152例患者的临床资料。结果本组资料平均手术时间为（189．5&#177;24．2）min清扫淋巴结数量平均为（30．4&#177;11．6）个，与传统手术相比明显增加；缩短了手术时间，减少了手术出血，手术视野清晰。本组资料术后无吻合口漏、淋巴漏、术后出血及手术死亡。结论新型超声刀在胃癌根治术中使用是安全的，并有助于提高胃癌淋巴结清扫的彻底性。     

The Value of Peritoneal Cytology as a Preoperative Predictor in Patients With Gastric Carcinoma Undergoing a Curative Resection

Background Although positive peritoneal cytology is associated with poor prognosis, it has not been found to be independently predictive of outcome when evaluated in context of post-resection pathologic T and N stage. This study was undertaken to evaluate the predictive value of positive cytology in context of other prognostic factors available prior to surgery in patients undergoing R0 resection for gastric cancer, to assess its role in selecting patients for appropriate treatment prior to surgical resection.Methods Clinical variables for all patients undergoing R0 resection for gastric adenocarcinoma at Memorial Sloan-Kettering Cancer Center from 1993–2002 were reviewed from a prospective database. Patients underwent preoperative assessment of T and N stage with CT scan, laparoscopy, and endoscopic and/or laparoscopic ultrasound. Peritoneal cytology was obtained in all patients.Results Patients with gastric cancer (n = 371) underwent R0 resection and staging laparoscopy with peritoneal washings; 24 patients (6.5%) had positive peritoneal cytology. Positive cytology was associated with advanced T stage (P = 0.02) but not with nodal positivity (P = 0.11). Median survival of patients with positive cytology was 14.8 months vs. 98.5 months for patients with negative cytology (P < 0.001). Multivariate analysis identified preoperative T stage, preoperative N stage, site, and cytology as significant predictors of outcome. Positive cytology was the preoperative factor most predictive of death from gastric cancer (RR 2.7, P < 0.001).Conclusions Positive cytology is information potentially available preoperatively that identifies a patient population at very high risk for early recurrence and death after curative resection of gastric cancer.Published by Springer Science+Business Media, Inc. © 2005 The Society of Surgical Oncology, Inc.     

351例胃癌术后患者的预后因素分析

目的 探讨胃癌术后影响胃癌患者生存的因素.方法 将2004年1月至2009年12月期间在笔者所在医院行手术治疗并获随访的351例胃癌患者作为研究对象,对其临床病理资料及随访资料进行单因素和多因素分析.结果 单因素分析显示患者年龄以及肿瘤部位、T分期、N分期、TNM分期和分化程度与预后有关(P＜0.05);多因素分析显示肿瘤部位、T分期、N分期和术后化疗是影响胃癌术后生存率的独立因素(P＜0.05).结论 肿瘤部位、浸润深度、淋巴结转移率及术后辅助化疗是影响胃癌术后生存的重要因素.对于有淋巴结转移或处于TNMⅢ期的胃癌患者,术后化疗可以提高其生存率.     

Significance of Tumor Length as Prognostic Factor for Esophageal Cancer

Our study indicated the relationship between tumor length and clinicopathologic characteristics as well as long-term survival in esophageal cancer. A total of 116 patients who underwent curative surgery for thoracic esophageal cancer with standard lymphadenectomy in 2 fields between 2000 and 2010 were included in the study. The medical records of these patients were retrospectively reviewed. The patients with tumor length ≥3 cm had a highly significant difference in the involvement of adventitia and lymph node stations. The patients with tumor length ≤3 cm had significantly lower rates of involvement of the adventitia and lymph node stations. Tumor length could have a significant impact on both the overall survival and disease-free survival of patients with resected esophageal carcinomas and may provide additional prognostic value to the current tumor, node, and metastasis staging system before patients receive any cancer-specific treatment.     

Tumor Diameter as a Prognostic Factor in Patients with Gastric Cancer

Background  The aim of this study was to evaluate the prognostic value of tumor diameter in gastric cancer. Methods  The study group comprised a series of 1215 patients who underwent curative gastrectomy. The appropriate tumor diameter cutoff value was determined. Prognostic factors were evaluated by univariate and multivariate analyses. Results  The tumor diameter cutoff value was 100 mm. Multivariate analysis showed that tumor site, macroscopic appearance, tumor diameter, depth of invasion, and presence of lymph node metastasis independently affected prognosis in all patients. Multivariate analysis of patients with larger tumors identified depth of invasion as an independent prognostic factor. A comparison between patients with smaller and larger tumors showed marked differences in the survival of those with stage II, IIIA, and IIIB tumors. A comparison of clinicopathological factors between stage II and III patients revealed that tumors occupying the entire stomach, ill-defined, undifferentiated, and serosa-penetrating tumors, and peritoneal metastases were far more frequent in patients with larger tumors. Conclusions  Tumor diameter in gastric cancer is a reliable prognostic factor that might be a candidate for use in the staging system. To improve outcomes for patients with tumors ≥100 mm in diameter, it is necessary to establish therapeutic strategies for peritoneal metastasis, particularly in stage II and III tumors.     

Borrmann Type IV: An Independent Prognostic Factor for Survival in Gastric Cancer

Background  Borrmann type IV gastric cancer has a poorer prognosis than other gastric carcinomas. This study compared the clinicopathological features of Borrmann type IV gastric cancer with those of other types of cancer and examined the significance of a Borrmann type IV carcinoma as a prognostic factor after gastrectomy. Methods  The clinicopathological features, tumor–node–metastasis (TNM) stage, and survival rates of 4,191 advanced gastric cancer patients, who had undergone a gastrectomy at the Samsung Medical Center between 1995 and 2005, were reviewed. Results  Borrmann type IV gastric cancer was found to be associated with more advanced and unfavorable clinicopathological features at diagnosis than the other cancers. The 5-year survival rate of the patients with Borrmann type IV cancer was 27.6%. In contrast, the 5-year survival rate of patients with the other types of cancer was 61.2%. The 5-year survival rate for each stage of Borrmann type IV gastric cancer and the other type gastric cancer was 61.0% and 88.8% for stage Ib (P < 0.001), 49.8% and 76.1% for stage II (P < 0.001), 36.4% and 55.1% for stage IIIa (P < 0.001), 15.2% and 38.5% for stage IIIb (P = 0.001), and 10.2% and 20.1% for stage IV (P = 0.008), respectively. Multivariate analyses revealed a Borrmann type IV carcinoma, the surgical extent, curability, tumor stage, including T, N, and M status, and adjuvant therapy to be independent prognostic factors for survival. Conclusion  A Borrmann type IV carcinoma has unique clinicopathological features compared with other types of gastric carcinomas and is an important independent prognostic factor.     

术前血清白蛋白水平对胃癌根治术患者的预后评估价值

目的探讨术前血清白蛋白水平对胃癌根治术患者的预后评估价值。方法回顾分析天津医科大学附属肿瘤医院2001年1月至2003年12月间行胃癌根治术的146例患者的临床病理资料,其中术前血清白蛋白正常者115例（〉35g／L,正常组）,降低者31例（≤35g/L,降低组）。结果血清白蛋白正常组和降低组术后分别有50例（43．5％）和28例（90．3％）复发,差异有统计学意义（P〈0．01）。两组术后5年生存率分别为57．4％和9．7％,差异有统计学意义（P〈O．01）。经多因素预后分析显示,术前血清白蛋白水平是胃癌根治术患者的独立预后因素（P〈0．01）。进一步分层分析显示,无论有无淋巴结转移,两组患者5年生存率的差异均有统计学意义（P〈0．05）;对于胃下部癌,两组患者5年生存率的差异有统计学意义（P〈0．01）;但对于胃中上部癌。两组差异则无统计学意义（P〉0．05）。结论术前血清白蛋白降低的胃癌患者（尤其胃下部癌者）根治术后预后不佳．应予以积极的术后辅助治疗．     

Gastric Cancer: Establishing Predictors of Biologic Behavior with Use of Population-Based Data

Background Tumor thickness and nodal status are important predictors of survival following curative resection for gastric cancer. Lymphovascular invasion (LVI) is a potential predictor of biological behavior. The relationship between LVI and tumor thickness (T status) has not been established in population-based studies.Methods Clinicopathological and survival data of 577 patients at nine centers, from between 1991 and 1997, was collected from patient records and a Provincial Cancer Registry. The primary endpoint of the study was death. A secondary analysis of a node-negative subgroup examined the significance of LVI with respect to T status.Results The population disease-specific survival was 28%. In a multivariate analysis, T, N, M, esophageal margin, tumor morphology, and residual tumor category were independent predictors of survival. LVI was documented in 58% of resected tumors. LVI correlated with advancing T and N status but was not significant in a multivariate population model. Subgroup analysis of node-negative gastric cancer found T status and LVI to be independent predictors of survival. LVI was associated with a 5-year survival of 8%, versus 43% among patients in whom it was absent (P < .001).Conclusions T status and N status were the most important independent predictors of survival in a population-based study of gastric cancer. LVI correlated with advancing N and T status. Multivariate analysis of node-negative patients showed LVI and T status are independent predictors of survival.     

p53 Accumulation Is a Prognostic Factor in Intestinal-Type Gastric Carcinoma but Not in the Diffuse Type

Background: The prognostic value of p53 nuclear accumulation in gastric cancer is still unclear, as shown by the discordant results still reported in the literature. In this study, we evaluated the correlation between p53 accumulation and long-term survival of patients resected for intestinal and diffuse-type gastric cancer.Methods: Eighty-three patients with carcinoma of the intestinal type and 53 patients with carcinoma of the diffuse type were included in the study. Immunohistochemical staining of the paraffin sections was performed by using monoclonal antibody DO1; cases were considered positive when nuclear immunostaining was observed in 10% or more of the tumor cells. Prognostic significance of different variables was investigated by univariate and multivariate analysis.Results: p53 positivity was found in 51.8% of intestinal-type and 50.9% of diffuse-type cases. No significant correlation between the rate of p53 overexpression and age, sex, tumor location, tumor size, depth of invasion, lymph node involvement, distant metastases, and surgical radicality was found in the two groups of patients. A statistically significant difference in survival rate was observed between p53-negative and p53-positive cases in the intestinal type (P < .05), confirmed by multivariate analysis (P < .005; relative risk = 3.09). On the contrary, no correlation with survival was found in diffuse-type cases according to p53 overexpression.Conclusions: These results suggest that the immunohistochemical detection of p53 accumulation is a useful indicator of poor prognosis in the intestinal but not in the diffuse type of gastric cancer, and are indicative of distinct molecular pathways and pattern of progression in the two histotypes.     

Correlation between Blood Flow Signal of Color Flow Imaging and Nottingham Prognostic Index in Patients with Breast Carcinoma

BACKGROUND: The purpose of this study was to investigate the relationship between blood supply detected by Doppler ultrasound and the Nottingham Prognostic Index (NPI) in breast cancer patients. PATIENTS AND METHODS: 137 patients with breast carcinoma, who had undergone color Doppler flow imaging (CDFI) and surgery, were involved in this retrospective study. CDFI was divided into 4 levels: absent (grade 0), minimal (grade 1), moderate (grade 2), and marked (grade 3). NPI was calculated as: NPI = 0.2 × tumor size (cm) + grade (I-III) + lymph node score (1-3). All patients were followed until the final observation (July 2010), or until the time of death. The survival state of the patients was divided into 3 categories: healthy survival, metastasis, and death. RESULTS: Blood signal grades were positively correlated with NPI (Spearman r = 0.55926, p < 0.0001) and survival state (χ(2) = 9.0248, p < 0.01). Patients with abundant blood flow signal (grade 2-3) had a significantly shorter overall survival than did those with limited blood flow signal (grade 0-1) (χ(2) = 5.0384, p = 0.0248). CONCLUSION: Flow signal measured by Doppler ultrasound may be useful as a prognostic indicator for patients with breast carcinoma.     

Soluble Intercellular Adhesion Molecule-1 as a Prognostic Marker for Stage II Colorectal Cancer Patients

Background Soluble intercellular adhesion molecule-1 (sICAM-1) represents a circulating form of ICAM-1 that is constitutively expressed or is inducible, which localizes to the cell surfaces of different cell lines and is related to the metastatic potential of cancer cells. The aim of the present study was to determine the relationships between the preoperative serum concentration of sICAM-1 and clinicopathological features, established tumor markers and prognosis, in colorectal cancer patients. Methods One hundred and thirty-eight patients with histologically proven colorectal cancer and 40 normal volunteers were included in this trial. Preoperative serum was collected, and sICAM-1 levels were assayed using a commercially available enzyme-linked immunosorbent assay kit. Results The mean sICAM-1 level in patients was significantly higher than that in controls, and increased with disease progression. The prognosis of patients with an elevated sICAM-1 level was significantly worse than that of patients with a normal sICAM-1 level. In a Cox multivariate analysis, the strongest prognostic factor in all patients was distant metastasis followed by sICAM-1 level, while in patients with stage II classification, the strongest prognostic factor was serum level of sICAM-1. The prognosis of stage II patients positive for sICAM-1 was comparable to that of stage III patients. Conclusions Preoperative sICAM-1 level is an independent prognostic marker for stage II colorectal cancer. Measuring serum sICAM-1 may provide valuable information, especially for stage II patients, when selecting appropriate candidates for adjuvant chemotherapy.     

Expression of Vascular Endothelial Growth Factor (VEGF) and Epidermal Growth Factor Receptor (EGFR) is an Independent Prognostic Indicator of Worse Outcome in Gastric Cancer Patients

BACKGROUND: Unlike other human tumors, gastric cancer remains a great therapeutic challenge since no standardized postoperative treatment exists. Knowledge of molecular pathways determining the behavior of individual gastric tumors seems to be crucial for therapeutic decisions, and evaluation of vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) expression might be critical for prognosis, assessment, and identification of patients that could be treated with tailored therapies. METHODS: VEGF and EGFR determination was performed in 88 gastric cancer samples as well as 25 normal gastric mucosa specimens from non-cancer patients using a commercially available immunohistochemistry kit. In all samples, the correlation of VEGF and EGFR expression was investigated with each other, and with other prognostic indicators in all samples, and, finally, with survival rates in 69 patients undergoing potentially curative surgery. RESULTS: Forty-eight per cent (42 cases) of gastric cancers expressed VEGF, and 44% (39 cases) stained for EGFR. In curatively treated patients, VEGF and EGFR expression was demonstrated to correlate with worse survival in both univariate and multivariate analyses. Molecular profiling was shown to more accurately estimate the risk of cancer-related death than TNM stage, and, of most interest, to allow sorting out high-risk patients within the same stage. CONCLUSIONS: These findings provide evidence that contemporary evaluation of VEGF and EGFR expression may be crucial to select gastric cancer patients with poor prognosis who may benefit of tailored treatments.     

Clinical Correlation of Endoscopic Ultrasonography with Pathologic Stage and Outcome in Patients Undergoing Curative Resection for Gastric Cancer

Background Endoscopic ultrasonography (EUS) is considered valuable for preoperative staging of gastric cancer and defining patient eligibility for enrollment in neoadjuvant protocols. The aim of this study was to correlate EUS staging with pathologic evaluation and outcome in patients undergoing curative R0 resection for gastric cancer. Methods All patients who underwent preoperative clinical assessment of T/N stage with EUS and subsequent R0 resection for gastric adenocarcinoma between 1993 and 2003 were identified from a prospective database. Patients who received neoadjuvant chemotherapy were excluded. Clinical staging results from preoperative EUS were compared with postoperative pathologic staging results and correlated with clinical outcome. Results Two hundred twenty-five patients with gastric cancer underwent EUS followed by R0 resection, without preoperative chemotherapy. The accuracy of the individual EUS T stage was 57% (127 of 223) and was 50% for N stage (110 of 218). Although EUS was less able to predict outcome according to individual T stage, patients with lesions ≤T2 on EUS had a significantly better outcome than patients with lesions ≥T3. Preoperative assessment of risk was not predicted by EUS N stage alone. Patients identified as high risk on EUS and those with a combination of serosal invasion and nodal disease had both the highest concordance with pathology and a significantly worse outcome (P = .02). Conclusions The concordance between EUS and pathologic results was lower than expected for individual T and N stages. Patients with lesions ≤T2 had a significantly better prognosis than patients with more advanced lesions. Individual EUS N stage has limited value in preoperative risk assessment. Combined assessment of serosal invasion and nodal positivity on EUS identifies 77% of patients at risk for death from gastric cancer after curative resection.