Hepsin在胃癌中表达下调并提示预后不良

背景:Ⅱ型跨膜丝氨酸蛋白酶hepsin在前列腺癌、卵巢癌、乳腺癌等多种原发肿瘤中呈高表达,并与肿瘤进展和预后不良相关。目的:探讨hepsin在胃癌中的表达模式及其与胃癌临床病理特征和预后的关系。方法:纳入40对原发性胃癌组织和相应正常胃黏膜,以cDNA微阵列技术筛选两者间的差异表达基因,并以real-time PCR进行验证。以免疫组化方法检测其中20例胃癌组织以及另100例胃癌组织石蜡切片中的hepsin蛋白表达,分析其表达与胃癌临床病理特征和预后的关系。结果:cDNA微阵列分析显示胃癌组织中的hepsin基因表达较正常胃黏膜显著下调(ratio=0.240),real-time PCR结果与cDNA微阵列分析一致(P=0.002)。83例(69.2%)胃癌组织hepsin蛋白表达阴性,其余为弱阳性表达。Kaplan-Meier曲线显示hepsin蛋白表达阴性者总体生存率显著低于hepsin蛋白表达弱阳性者(P<0.0001)。单因素分析显示hepsin蛋白表达与胃癌浸润深度(P=0.043)和患者总体生存率(P=0.018)相关,多因素Cox回归分析显示hepsin蛋白表达为胃癌预后的保护因素(RR=0.599,P=0.000)。结论:Hepsin在胃癌组织中表达下调,并与胃癌进展和预后不良相关。     

Decreased Expression of Monocyte Chemoattractant Protein-1 Predicts Poor Prognosis Following Curative Resection of Colorectal Cancer

Purpose  The significance of monocyte chemoattractant protein-1 in colorectal cancer is not well understood. The aim of this study was to investigate the significance of monocyte chemoattractant protein-1 expression in colorectal cancer patients undergoing potentially curative surgery. Methods  We studied 101 colorectal cancer patients who underwent potentially curative surgery. The concentration of monocyte chemoattractant protein-1 in the tumor and normal mucosa were measured. The expression of monocyte chemoattractant protein-1 was also evaluated immunohistochemically. Results  The tissue concentration of monocyte chemoattractant protein-1 in the tumor was significantly higher than that in the normal mucosa. The decreased monocyte chemoattractant protein-1 cancer/normal ratio was associated with lymph node involvement and could predict poor prognosis. On univariate analysis, the decreased monocyte chemoattractant protein-1 ratio, carcinoembryonic antigen levels, and serosal invasion were the significant factors for poor prognosis. Multivariate analysis showed that monocyte chemoattractant protein-1 ratio was the only independent risk factor predictive of a poor prognosis. Immunohistochemically, monocyte chemoattractant protein-1 was expressed in the cytoplasm. Conclusion  The decreased monocyte chemoattractant protein-1 ratio was an independent factor predicting poor prognosis in patients undergoing potentially curative surgery. Monocyte chemoattractant protein-1 deficiency may present a new therapeutic approach for colorectal cancer.     

Co-Expression of LGR5 and CD133 Cancer Stem Cell Predicts a Poor Prognosis in Patients With Gastric Cancer

BackgroundThe LGR5 and CD133 have been identified as cancer stem cells (CSCs) marker and prognostic marker in several cancers including gastric cancer. The purpose of the present study was to determine the association between co-expression of CSCs marker LGR5 and CD133 in patients with gastric cancer and their clinicopathological outcomes; to analyze the efficacy of co-expression of both markers in evaluating the prognosis of gastric cancer.Methods: LGR5 and CD133 expression were investigated in a total of 400 patients by using immunohistochemistry. Results were analyzed in association with patient characteristics outcomes. Overall survival was performed using Kaplan-Meier Curve analysis.ResultsLGR5 and CD133 were found positive in 219/400 (54.75%) and 251/400 (62.75%) respectively in gastric cancer tissues. Co-expression of LGR5 and CD 133 were significantly associated with poor clinicopathological outcomes, including lymphatic invasion, vascular invasion, higher pathological T stage, and higher TNM staging (stage IV) (P < .05). The overall survival of patients who were positive for LGR5 and CD133 had shorter than that of LGR5 and CD133-negative gastric cancer, especially in patients who were positive for both markers.ConclusionOur finding indicates that co-expression of LGR5 and CD133 could be used as a marker indicating poor prognosis, which can provide information for selected effective treatment and carried out of intensive follow-up in gastric cancer patients.     

Septic Complications and Prognosis After Surgery for Rectal Cancer

PURPOSE: The influence of septic complications on long-term prognosis after surgery for rectal cancer is controversial. This study was performed to investigate whether an abdominal or perineal septic complication was associated with rectal cancer recurrence. METHODS: A total of 228 patients who had undergone curative resection for rectal cancer from 1973 to 1992 were reviewed. The patients were divided into groups of those who developed either an intra-abdominal abscess or a perineal infection after surgery (infection group) and those who did not (noninfection group). RESULTS: There was no clear difference in the overall incidence of tumor recurrence between the infection group (19/53, 36 percent) and the noninfection group (46/175, 26 percent; P = 0.25). However, the incidence of local recurrence was higher in the infection group (12/53, 23 percent) than in the noninfection group (16/175, 9 percent; P = 0.02). This increased risk was restricted to patients with a perineal infection (10/30, 33 percent; P = 0.003 vs. the noninfection group), whereas patients with an abdominal infection (3/24, 13 percent) did not differ from the noninfection group. CONCLUSION: Patients with a perineal infection after an abdominoperineal resection have an increased incidence of local recurrence. However, there was no association between abdominal sepsis and prognosis after surgery for rectal cancer.     

Reduced Red Blood Cell Count Predicts Poor Survival After Surgery in Patients With Primary Liver Cancer

Currently, the optimal therapy of primary liver cancer (PLC) remains to be hepatic resection. For better management of the patients, we evaluated the prognostic predicting value of red blood cell (RBC) count, a routine laboratory parameter, on the long-term survival of patients who underwent surgical treatment.Clinical and laboratory data of 758 patients, who underwent surgical hepatic resection, were retrospectively studied by χ² tests and logistic regression. All patients were enrolled at Henan Cancer Hospital, Zhengzhou, China, from February 2009 to July 2013, and none of them received any other treatments before surgery. Kaplan–Meier survival analysis and Cox proportional hazard models were used to examine the influence of RBC counts on patients’ survival.The Cox univariate and multivariate analyses showed that preoperative RBC count was an independent risk factor of poor prognosis after surgical treatment. The Kaplan–Meier curves showed that the overall survival (OS) of patients without reduced preoperative RBC counts was significantly better than those patients with reduced preoperative RBC counts (P < 0.001). Concordantly, compared with the patients with either reduced preoperative and/or postoperative RBC counts, patients without reduced RBC counts preferred to be low Child–Pugh grades (P = 0.0065), which implies a better hepatic function. In addition, low RBC count was found to be significantly associated with patients of female (P = 0.003), younger age (P =  < 0.001), and with higher AST/ALT ratio (P = 0.005).This study revealed that patients with preoperative RBC counts lower than normal had worse OS rates than those without reduced preoperative RBC counts, perhaps due to the significant correlation of reduced preoperative RBC count to patients’ worse Child–Pugh grade that reflect the loss of liver functions.     

Distilled Water Peritoneal Lavage After Colorectal Cancer Surgery

PURPOSE Tumor cells exfoliated into the peritoneal cavity during colorectal cancer surgery are viable and tumorigenic and may contribute to peritoneal recurrence. Although commonly used, the tumoricidal effectiveness of antiseptics in peritoneal lavage is doubted because of their chemical alteration by peritoneal secretions. In contrast, osmotic lysis by incubation in distilled water may offer an effective tumoricidal activity. Data defining the susceptibility of colorectal carcinoma cells to osmotic lysis are lacking and hence there is no consensus on optimal lavage methodology.METHODS We examined the cytocidal activity of water on colorectal cancer cell lines in culture and determined the effect of peritoneal secretions in vivo on the tumoricidal effectiveness of water.RESULTS Incubation of cells in distilled water resulted in cell lysis, with 100 percent lysis achieved after 14 minutes of incubation. In vivo, contamination of lavage water by peritoneal secretions produced a resultant solution with an osmolality of 50 mM. Sequential lavages reduced this contamination, enabling a final resultant solution with an osmolality of 10 mM, which produced 100 percent cell lysis after 32 minutes of incubation.CONCLUSIONS Current peritoneal lavage methodology is inadequate because complete cell lysis requires water incubation for longer time periods than is currently practiced. Solutions to this problem are discussed.     

Signet Ring Cell Histology Is Not an Independent Predictor of Poor Prognosis After Curative Resection for Gastric Cancer: A Propensity Analysis by the KLASS Group

Whether signet ring cell (SRC) histology carries a worse prognosis than other forms of gastric adenocarcinoma has been questioned. The present study investigated the differences in clinicopathologic features and survival between SRC and non-SRC adenocarcinoma. The prospectively collected data of 2643 patients who had undergone curative gastrectomy between 1998 and 2005 by 10 surgeons were reviewed. Additionally, we employed analysis of covariance, propensity-score risk adjustment, and propensity-based matching to account for possible selection bias. The baseline characteristics of prematched patients with SRC or non-SRC adenocarcinoma histology differed: SRC presented in younger patients and less often in men, was more likely found in the middle stomach, and was more likely to be Stage I. After applying the propensity-score strata and propensity-score matching, there was no difference in the baseline characteristics, and SRC was not an independent risk factor for mortality in the same stage. SRC is not an independent predictor of poor prognosis after curative resection for gastric cancer in Korea.     

Colorectal Cancer After Gastric Surgery: A Meta-Analysis

Background: Until now, the question of whether previous gastric surgery results in an increased risk of colorectal cancer has remained controversial. A meta-analysis was performed to resolve this issue. Methods: The numbers of colorectal tumors in the two populations with the and without gastric surgery were retrieved from all relevant articles found through a MEDLINE search. If available, the most detailed breakdown of the data by patient gender, type of peptic ulcer, type of surgery, time since gastric surgery, and by tumor location was chosen. The Mantel-Haenszel procedure was used to calculate a weighted odds ratio from the individual studies. The method of DerSimonian and Laird was used to calculate a weighted average of the difference between tumor rates in patients with and without gastric surgery. Results: The summary odds ratio was 1.09 with a 95% confidence interval of 0.96–1.24. The length of time after surgery, gender, tumor location, initial ulcer type, and different types of surgery were not associated with any significant influence. The summary rate difference was not significantly different from zero. The test for heterogeneity yielded a χ²= 26.87, df = 13, p = 0.013. After ignoring one obvious outlier study, the χ² test dropped to a nonsignificant level. A L'Abbé plot failed to show any prevailing influence of rate size on the overall heterogeneity among the various studies. Conclusions: Surgery for peptic ulcer does not result in an increased risk for colorectal tumors. This lack of influence was shown consistently by all tests of the present meta-analysis.     

The Profile of Serum microRNAs Predicts Prognosis for Resected Gastric Cancer Patients Receiving Platinum-Based Chemotherapy

Background and Aim

Adjuvant chemotherapy is an important component in the treatment of gastric cancer (GC) patients; however, some patients do not respond to the drugs. We aimed to develop a practical profile based on serum microRNAs (miRNAs) that can be used to predict patients likely to respond to treatment.

Methods

Microarrays were used to screen cisplatin-resistant SGC7901/DDP GC cells and the parental SGC7901 cell lines for miRNAs related to chemotherapy sensitivity. The correlation between the expression patterns of identified serum miRNAs and overall survival was confirmed in 68 GC patients. Furthermore, we also validated the signature of the serum miRNAs in an independent cohort of 50 GC patients.

Results

From the screening microarrays, we focused on miR-15a, miR-15b and miR-93 as downregulated miRNAs in the SGC7901/DDP cells and miR-27a, miR-106a and miR-664 as upregulated miRNAs. Only serum miR-106, miR-15a, miR-93 and miR-664 were useful in predicting the prognosis of patients who received adjuvant chemotherapy. We identified a signature of four serum miRNAs (miR-106, miR-15a, miR-93 and miR-664) that, when combined, can be used as a risk score for overall survival. Patients with a higher risk score had worse prognosis (p < 0.05). For the independent cohort of patients, the signature of the four miRNAs predicted prognosis well.

Conclusion

Our data showed that the risk score derived from the four serum miRNAs was closely associated with the overall survival in GC patients who received adjuvant chemotherapy.

     

Impact of Blood Transfusions on Recurrence and Survival After Rectal Cancer Surgery

Purpose This study was designed to determine whether type or number of blood units transfused affected short-term and long-term outcome in patients undergoing surgery for rectal cancer. The number of perioperative blood units is associated with postoperative mortality and overall survival by some authors. In addition, allogenic perioperative blood transfusion has been postulated to produce host immunosuppression and has been reported to result in adverse outcome in patients with colorectal cancer. Autologous blood transfusion might improve results compared with allogenic transfusion. Methods Clinical outcome for 597 patients undergoing surgery for rectal cancer was analyzed according to their transfusion status. Results for type (autologous or allogenic) and number of blood units transfused were recorded. Results Blood transfusion was associated with increased postoperative mortality at 60 days. Patients who received > 3 units had a postoperative mortality of 6 percent compared with 1 percent for patients who received 1 to 3 units and 0 percent for patients who did not require transfusions. No difference was found between patients who received autologous or allogenic blood. Blood transfusions were also associated with impaired overall survival in a univariate analysis, but this finding was not confirmed in the multivariate analysis. The number or type of blood units transfused did not influence oncologic results. Local recurrence rates, distant metastases rates, and disease-free survival were not influenced by transfusion in our patients. Conclusions Increased numbers of blood units were associated with postoperative mortality. However, there is no reason, with respect to cancer recurrence or disease-free survival, to use a program of transfusion with autologous blood in patients undergoing surgery for rectal cancer. Reprints are not available.     

Serosal Invasion Strongly Associated With Recurrence After Curative Hepatic Resection of Hepatocellular Carcinoma: A Retrospective Study of 214 Consecutive Cases

The purpose of this study was to clarify the individual prognostic factors after curative and primary resection of hepatocellular carcinoma (HCC).Reliable prognostic factors and tumor staging for HCC have been required to predict an appropriate prognosis. However, in HCC, no staging system has received universal acceptance, and several tumor factors seem to relate to HCC prognosis, but they are not definitive. At present, few studies have mentioned the importance of serosal invasion as a prognostic factor.A retrospective search of our database identified 214 consecutive patients who underwent primary and curative hepatectomy for HCC at our department between January 1998 and December 2011. Risk factors for recurrence-free survival (RFS) and overall survival (OS) were analyzed with Cox proportional hazard model, Kaplan-Meier method, and log-rank tests.Multivariate analyses showed that serosal invasion (hazard ratio [HR], 2.75; P = 0.0005) and vascular invasion (HR, 1.71; P = 0.0331) were independently correlated with RFS. Serosal invasion was significantly correlated with HCC recurrence (P = 0.0230). The Kaplan–Meier method and log-rank tests revealed that the patients with serosal invasion showed significantly worse prognosis both in RFS (P < 0.0001) and OS (P = 0.0016).Serosal invasion should be regarded as a strong independent predictor for recurrence in curatively resected HCC cases.     

Patterns of Surveillance Practices After Curative Surgery for Colorectal Cancer in a French Population

PURPOSE Despite controversies, postoperative surveillance of colorectal cancer is generally recommended. This registry-based study was designed to assess the adherence of surveillance practices to French guidelines and identify three-year surveillance patterns and their demographic and clinical determinants. METHODS All patients (N = 409) diagnosed with first colorectal cancer in 1998 and alive without recurrence at least six months after curative surgery were identified from a population-based registry. Medical charts from multiple sources were reviewed to collect exhaustive information on follow-up procedures used during a three-year period. Multiple correspondence and cluster analyses were used to identify surveillance patterns. RESULTS The proportion of patients with a lower surveillance than that recommended was 35 percent for clinical examination, 65 percent for abdominal ultrasound, 52 percent for chest x-ray, and 20 percent for colonoscopy. Cluster analysis identified three patterns called minimal, moderate, and intensive surveillance patterns, which included 47, 24, and 29 percent of the patients respectively. The main independent predictors of both moderate and intensive surveillance patterns vs. minimal pattern were advanced tumor stage, chemotherapy, and radiation therapy. Younger age also was strongly associated with the intensive surveillance pattern, and the presence of symptoms with the moderate surveillance pattern. CONCLUSIONS Adherence of surveillance practices to French guidelines seems relatively poor. Surveillance patterns are mainly explained by patient age, tumor stage, and treatment modalities. Supported by a 2001 PHRC grant (Programme Hospitalier de Recherche Clinique) from the French Health Ministry. M. Boulin was supported by a grant from the Fondation pour la Recherche Médicale. Presented at the Association des Epidémiologistes de Langue Fran?aise Conference, Bordeaux, France, September 16 to 18, 2004.     

Tumor Budding at the Invasive Margin Can Predict Patients at High Risk of Recurrence After Curative Surgery for Stage II,T3 Colon Cancer

PURPOSE: The aim of this study was to identify indicators that can predict patients at high risk of tumor recurrence in Stage II, T3 colon cancer. METHODS: A total of 138 patients classified as Stage II, T3 underwent curative resection of colon cancer between 1981 and 1993. Clinical variables included age, gender, bowel obstruction, tumor location, and emergency presentation. For each colon tumor specimen, the following histopathological variables were assessed: maximum tumor diameter (<5 vs. 5 cm), depth, tumor grade (well and moderate vs. other), lymphatic and venous invasion (absent vs. present), perineural invasion, tumor necrosis, and tumor margin (expanding vs. infiltrating). We also categorized tumor budding, defined as a single cancer cell or small clusters of undifferentiated cancer cells in the invasive frontal lesion, into two categories: none or minimal (BD-1), and moderate or severe (BD-2). Univariate analysis for factors regarding recurrence and disease-specific survival were performed with the logistic regression model and the log-rank test. RESULTS: Among the factors analyzed, tumor budding was the only factor that was significantly associated with recurrence and survival. The numbers of patients with BD-1 and BD-2 tumors were 111 and 27, respectively. Forty-eight percent of BD-2 tumor patients developed recurrence, compared with 4.5 percent of BD-1 tumor patients (P < 0.0001). The cumulative disease-specific survival rates at five years for patients with BD-1 and BD-2 tumors were 98 and 74 percent, respectively (P < 0.0001). CONCLUSION: The presence of moderate or severe budding at the invasive margin in Stage II, T3 colon cancer indicated a high risk of tumor recurrence after curative surgery, providing useful information for the decision regarding postoperative adjuvant chemotherapy.     

Increased Expression of CSF-1 Associates With Poor Prognosis of Patients With Gastric Cancer Undergoing Gastrectomy

Clinical significance of diametrically polarized tumor-associated macrophages in gastric cancer has been elucidated in our previous study, whereas the role of cytokines that orchestrate tumor-associated macrophages polarization in gastric cancer remains elusive. The study aims to evaluate the prognostic value of colony-stimulating factor-1 expression in patients with gastric cancer.We examined the colony-stimulating factor-1 expression in tumor tissues by immunohistochemical staining in retrospectively enrolled 365 patients with gastric cancer undergoing gastrectomy at Zhongshan Hospital during 2008. Kaplan–Meier analysis and Cox regression models were used to evaluate the prognostic value of colony-stimulating factor-1 expression and its association with clinicopathological factors. A predictive nomogram by integrating colony-stimulating factor-1 expression with the TNM staging system was generated for overall survival evaluation of the patients.High colony-stimulating factor-1 expression predicted an unfavorable outcome in gastric cancer. The colony-stimulating factor-1 expression in tumor tissue could give a further discrimination for the prognosis of gastric cancer patients. Cox multivariate analysis identified the colony-stimulating factor-1 expression as an independent prognostic factor. The generated nomogram performed well in predicting the 3- and 5-year overall survival of gastric cancer patients.The colony-stimulating factor-1 is a potential independent adverse prognosticator for gastric cancer patients, which could be integrated with the tumor-associated macrophages staging system to improve the predictive accuracy for overall survival, especially in advanced tumors.     

POSSUM Predicts Decreased Overall Survival in Curative Resection for Colorectal Cancer

Purpose Poor condition at operation determined by the physiologic POSSUM score is related to postoperative mortality and morbidity of colorectal cancer surgery. This study was designed to analyze the relationship between condition of patients with colorectal cancer at operation and long-term overall survival. Methods A total of 542 patients survived a radical resection for Stages I, II, or III colorectal cancer. Physiologic POSSUM score at surgery, exclusive of age, was calculated for all patients. Mean physiologic POSSUM score was used as cutoff point to determine low-risk and high-risk group patients. A Cox proportional hazard analysis was performed to study the effect of low-risk and high-risk group on overall survival and to identify independent risk factors. Results Five-year overall survival was significantly higher in low-risk group patients than in high-risk group patients (low-risk group 66.6 percent vs. high-risk group 48.5 percent; P < 0.001). Differences in overall survival also were found when patients in Stages I, II, and III were analyzed separately. Risk factors for overall survival were advanced stage of disease, poor tumor differentiation, mucinous adenocarcinoma, older than age 70 years, and poor condition of the patient at time of operation. Conclusions Poor condition at operation, as determined by physiologic POSSUM score, is a risk indicator for long-term overall survival in colorectal cancer patients. Poster presentation at the meeting of the European Association of Coloproctology, Geneva, Switzerland, September 16 to 18, 2004. Reprints are not available.     

The Tumor-immune Index is Correlated With the Prognosis of Patients After Curative Resection for Nonsmall Cell Lung Cancer

We developed a novel tumor-immune index (TII) based on carcinoembryonic antigen levels, lymphocyte counts, and platelet counts, and explored its prognostic value in nonsmall cell lung cancer (NSCLC).The prognostic value of the TII was evaluated based on a retrospective study of 205 patients with early NSCLC, who underwent resection in the whole year of 2006, and validated in another group of 228 patients enrolled in the next year of 2007.The optimal cut-off point for the TII was 578 × 10⁻⁹, and this value was used to stratify patients with NSCLC into low TII (≤578 × 10⁻⁹) and high TII (>578 × 10⁻⁹) groups. Univariate and multivariate analyses revealed that high TII was an independent predictor for overall survival and recurrence-free survival in both the training and validation cohorts. The areas under the curve of the TII for survival and recurrence were significantly larger than those for tumor, node, metastasis (TNM) stage and carcinoembryonic antigen. In the subgroup analysis, the TII was also significantly correlated with overall survival (P = 0.001, P = 0.009, and P = 0.007 in the TNM I, II, and IIIa subgroups, respectively) and recurrence-free survival (P < 0.001, P = 0.006, and P = 0.014 in the TNM I, II, and IIIa subgroups, respectively). Similarly, for patients with N2-positive tumors, the overall survival and recurrence-free survival rates for patients in the high TII group were also significantly lower than the respective values for patients in the low TII group (P = 0.026 and P = 0.007, respectively).The TII can be used to distinguish patients with similar pathologies and stages into high and low-risk categories based on the probability of recurrence according to a convenient blood-based test.