胃癌腹膜转移的临床病理特性及预后分析

目的 探讨胃癌腹膜转移(P2)的临床病理特性及不同术式对预后的影响。方法 对91例P2患者的临床病理资料及不同术式术后生存情况进行回顾性分析。结果 单因素分析发现,肿瘤大小、肿瘤部位、分化程度、Borrmann分型、脏器侵犯、淋巴结转移、浸润深度、肝转移与P2相关(P＜0.05)。Logistic回归分析显示,浸润深度和脏器侵犯是P2独立的影响因素(P＜0.05)。非根治切除术组和姑息手术组在年龄、腹水及脏器侵犯上差别有统计学意义(P＜0.05)。姑息手术组中造瘘术、胃肠吻合术与剖腹探查术间的生存时间差别无统计学意义(P＞0.05)。非根治切除术组的中位生存时间为13.4月,姑息手术组的中位生存时间为4.2月,差别有统计学意义(P＜0.01),Cox分析显示手术方式和肿瘤大小是影响P2患者预后的独立危险因素。结论 胃癌患者的临床病理特征与腹膜转移的发生密切相关,非根治切除术可改善胃癌腹膜转移(P2)患者的预后。     

胃癌外周神经侵犯与ＥＧＦＲ及预后的相关性研究

目的　检测外周神经侵犯（ＰＮＩ）在人胃癌中的发生情况,探讨其与表皮生长因子受体（ＥＧＦＲ）的相关性以及对胃癌预后的影响。方法　检测６６９例胃癌组织石蜡切片中神经侵犯的发生情况及ＥＧＦＲ的表达情况,分析神经侵犯与胃癌临床病理参数的关系及其在胃癌患者预后中的价值。结果　ＰＮＩ的发生与浸润深度、癌栓、淋巴结转移、ＴＮＭ分期及ＥＧＦＲ表达均相关。单因素生存分析显示,ＰＮＩ阳性组的５年生存率为２６.４％,低于阴性组的４３.３％（Ｐ＜０.０５）。结论　胃癌患者发生ＰＮＩ与预后有关,并提示预后不良,ＥＧＦＲ可能是参与胃癌发生ＰＮＩ的因素之一。     

Two rare cases of node-positive differentiated gastric cancer despite their infiltration to sm1, their small size, and lack of lymphatic invasion into the submucosal layer

Early gastric cancer without lymph node metastasis has been reported after the analysis of many cases, and a consensus has been reached about this condition. We report two cases of node-positive differentiated sm1 gastric cancer without lymphatic invasion into the submucosal layer. Case 1 was a 73-year-old man who underwent EMR for 0-IIc early gastric cancer (EGC) on the gastric angle, with a histological diagnosis of tub1. Pathological examination revealed a 0-IIc lesion that was 12 mm in size and sm1 in invasion depth without lymphatic-vascular invasion. However, the infiltration in the submucosal layer was relatively wide. The patient subsequently underwent distal gastrectomy with D2 lymph node dissection. Pathological examination revealed level 2 lymph node metastasis. Case 2 was a 62-year-old woman who underwent ER for a 0-I+IIc-type EGC on the greater curvature of the antrum, with a histological diagnosis of tub1. Pathological examination revealed a 0-I+IIc-type lesion that was 15 mm in size and sm1 in depth. Lymphatic invasions in the muscularis mucosa were found, but none were seen in the submucosal layer. Two years later, follow-up computed tomography (CT) showed a lymph node swelling in the infrapyloric region. Distal gastrectomy with D2 dissection was then performed, and pathological examination revealed level 1 lymph node metastasis. Although the lesions in both patients satisfied the criteria of Gotoda et al. for minimal risk of nodal involvement, lymph node metastasis was observed in these patients. Curative surgery with lymph node dissection is thus required in patients with wide infiltration of the submucosal layer or lymphatic invasion in the muscularis mucosa.     

胃腺癌患者转移部位对预后的影响

目的探讨远处转移部位与胃腺癌患者预后的关系。 方法利用美国SEER数据库中2010年1月至2014年12月间诊断为胃腺癌伴远处转移的病例,Kaplan Meier法绘制生存曲线,采用Cox比例风险回归模型分析影响总生存、肿瘤特异性生存的独立因素。 结果共6532例病例纳入本研究,其中骨转移784例、脑转移126例、肝转移2692例、肺转移958例和远处淋巴结转移2321例。单器官转移患者中,骨转移者较肝转移者的总生存、肿瘤特异性生存差;远处淋巴结转移者较骨转移、肝转移、肺转移、脑转移者的总生存、肿瘤特异性生存好。Cox多因素分析表明,在已发生远处转移的胃腺癌患者中,男性、高龄、未婚、低分化、未行原发灶手术或多器官转移者的总生存和肿瘤特异性生存均较差。 结论不同转移部位对胃癌患者预后的影响不尽相同。在单器官转移的胃腺癌患者中,骨转移患者较肝或远处淋巴结转移者的预后差。对于胃腺癌伴远处转移的患者,男性、高龄、未婚、低分化、未行原发灶手术或多器官转移是影响预后的独立危险因素。     

Prognostic significance of serum inflammation indices for different tumor infiltrative pattern types of gastric cancer

BACKGROUNDInflammatory indices are considered to be potential prognostic biomarkers for patients with gastric cancer (GC). However, there is no evidence defining the prognostic significance of inflammatory indices for GC with different tumor infiltrative pattern (INF) types.AIMTo evaluate the significance of inflammatory indices and INF types in predicting the prognosis of patients with GC.METHODSA total of 962 patients who underwent radical gastrectomy were retrospectively selected for this study. Patients were categorized into the expansive growth type (INFa), the intermediate type (INFb), and the infiltrative growth type (INFc) groups. The cutoff values of inflammatory indices were analyzed by receiver operating characteristic curves. The Kaplan–Meier method and log-rank test were used to analyze overall survival (OS). The chi-square test was used to analyze the association between inflammatory indices and clinical characteristics. The independent risk factors for prognosis in each group were analyzed by univariate and multivariate analyses based on logistic regression. Nomogram models were constructed by R studio.RESULTSThe INFc group had the worst OS (P < 0.001). The systemic immune-inflammation index (P = 0.039) and metastatic lymph node ratio (mLNR) (P = 0.003) were independent risk factors for prognosis in the INFa group. The platelet-lymphocyte ratio (PLR) (P = 0.018), age (P = 0.026), body mass index (P = 0.003), and postsurgical tumor node metastasis (pTNM) stage (P < 0.001) were independent risk factors for prognosis in the INFb group. The PLR (P = 0.021), pTNM stage (P = 0.028), age (P = 0.021), and mLNR (P = 0.002) were independent risk factors for prognosis in the INFc group. The area under the curve of the nomogram model for predicting 5-year survival in the INFa group, INFb group, and INFc group was 0.787, 0.823, and 0.781, respectively.CONCLUSIONThe outcome of different INF types GC patients could be assessed by nomograms based on different inflammatory indices and clinicopathologic features.     

Impact of HER-2 overexpression/amplification on the prognosis of gastric cancer patients undergoing resection: a single-center study of 1,036 patients

Background.

Opinions regarding the impact of human epidermal growth factor receptor (HER)-2 overexpression or HER-2 amplification on the prognosis of gastric cancer patients are mixed. The present study attempted to clarify this issue by investigating a large cohort of surgical patients.

Methods.

We investigated 1,036 gastric cancer patients undergoing curative-intent resection. Their surgical specimens were evaluated for HER-2 expression by immunohistochemistry (IHC), and those with HER-2 expression levels of 2+ were additionally subjected to fluorescence in situ hybridization (FISH). Data on demographic and clinicopathological features and relevant prognostic factors in these patients were analyzed.

Results.

HER-2 positivity was noted in 64 (6.1%) of 1,036 gastric cancer patients, including 46 patients whose HER-2 expression level was 3+ on IHC and 18 patients whose FISH results were positive. On univariate analysis, HER-2 positivity was more often associated with differentiated histology, intestinal type, and negative resection margins, whereas only differentiated histology was independently associated with HER-2 positivity in a logistic regression model. For stage I–IV gastric cancer, HER-2 was not a prognostic factor. In a subpopulation study, although HER-2 positivity emerged as a favorable prognostic factor for stage III–IV gastric cancer on univariate analysis, it failed to be an independent prognostic factor after multivariate adjustment.

Conclusions.

The prevalence of HER-2 positivity, determined using standardized assays and scoring criteria in a large cohort of gastric cancer patients after resection, was 6.1%. HER-2 positivity was phenotypically associated with differentiated histology. HER-2 is not an independent prognostic factor for gastric cancer.     

Over-expression of metastasis-associated in colon cancer-1 (MACC1) associates with better prognosis of gastric cancer patients

Objective: The aim of this study was to detect metastasis-associated in colon cancer-1 (MACC1) expression in Chinese gastric cancer and analyze the relationship between MACC1 expression and postoperative survival. Methods: The expression of MACC1 and c-MET protein in a sample of 128 gastric cancer tissues was detected by immunohistochemistry. A retrospective cohort study on the prognosis was carried out and data were collected from medical records. Results: The positive rate of MACC1 protein expression in gastric cancer was 47.66%, higher than that in adjacent noncancerous mucosa (P<0.001). MACC1 protein expression was not related to the clinicopathological variables involved. Kaplan-Meier analysis revealed that the survival of MACC1 positive group tended to be better than that of MACC1 negative group, particularly in patients with stage III carcinoma (P=0.032). Cox regression analysis revealed that MACC1 protein over-expression in gastric cancer tended to be a protective factor with hazard ratio of 0.621 (P=0.057). Immunohistochemical analysis showed that the positive rate of c-MET protein expression was much higher in cases with positive MACC1 expression in gastric cancer (P=0.002), but P53 expression was not associated with MACC1 expression. Conclusion: MACC1 over-expression implies better survival and may be an independent prognostic factor for gastric cancer in Chinese patients.     

胃癌组织中微血管数量与肝转移的关系

目的 本试验拟通过对胃癌组织中微血管的数量、血管分布方式的检测,探讨其与肝转移的关系。方法 收集胃癌石蜡标本７５例,其中肝转移２９例,采用兔抗人第Ⅷ因子相关抗体,ＳＡＢＣ免疫组化方法,在２００倍镜下计数每个病例癌组织中的血管数,以均值作为区分高、低血管组的标准。按血管在癌组织中的分布方式分为：肿瘤内型和间质型。检测,胃癌组织中的微血管数量和分布方式,比较与肝转移的关系。结果 全组病例的微血管数范围     

Clinical significance of skip metastasis in patients with gastric cancer

Background Metastasis appearing to bypass or skip tiers of lymph nodes (LNs) has been referred to as skip metastasis. The clinical impact of skip metastasis in gastric cancer remains unclear. Methods In patients with gastric cancer, the clinicopathological features and postoperative prognoses of 21 patients with skip metastasis were evaluated and compared with findings in patients with group 1 (N1) or group 2 (N2) LN metastasis. Results Of the 21 patients with skip metastasis, 9 patients had metastasis in the LN along the common hepatic artery (No. 8a), 8 patients had metastasis in the LN along the left gastric artery (No. 7), 2 patients had metastasis in LNs No. 7 and No. 8a, 1 patient had metastasis in the LN at the splenic hilum (No. 10), and 1 patient had metastasis in LN No. 10 and the LN along the splenic artery (No. 11). The mean diameter of the tumors in the patients with skip metastasis was 5.7 ± 2.4 cm, which was significantly smaller than those in the N1 patients (7.9 ± 4.1 cm) and N2 patients (9.3 ± 4.6 cm). The incidence of serosal invasion, lymphatic vessel invasion, and peritoneal metastasis was lower in patients with skip metastasis compared with N2 patients. The 5-year survival rates were 70.2%, 62.0%, and 31.2% in patients with skip metastasis, patients with metastasis in group 1 LNs, and those with metastasis in group 2 LNs, respectively. The prognosis of patients with metastasis in group 2 LNs was significantly worse than that of patients with either skip metastasis (P = 0.0029) or metastasis in group 1 LNs (P < 0.0001). Conclusion Our data indicate that both the clinicopathological characteristics and the prognoses of patients with skip metastasis were similar to those of patients with N1 LN metastasis, but these features were not similar to those in patients with N2 LN metastasis. The sites of skip metastasis presented in the current study may be the key for applying the concept of the sentinel node in gastric cancer.     

Impact of immunohistochemically identified lymphatic invasion on nodal metastasis in early gastric cancer

Background Among various clinical and pathological findings, lymphatic invasion (Ly) is the strongest risk factor for nodal metastasis in gastric cancer. However, the diagnosis of Ly is subjective and often inaccurate because of the difficulty of detecting lymphatic vessels with conventional hematoxylin and eosin (HE) staining. Methods The distribution of lymphatics in the normal gastric wall was immunohistochemically characterized using a new selective marker of lymphatic endothelium, D2-40, in surgical specimens resected for early gastric cancer (EGC). Then, Ly in the primary lesion was reevaluated, and the positive (PPV) and negative (NPV) predictive values for nodal metastasis were comparatively examined for Ly detected by HE staining (Ly-HE) and by immunohistochemical staining (Ly-IM) in 131 cases of EGC. Results D2-40-positive lymphatic vessels were observed in the deep proper mucosal layer, and the lymphatic vessel density (LVD) was extremely high in the muscularis mucosa (MM) layer. The number of Ly-IM-positive cases (15/131) was higher than the Ly-HE-positive cases (10/131). In 48 cases of intestinal-type cancer, Ly-IM had a PPV of 33.3% (2/6) and anNPV of 100% (42/42), which was more accurate than the corresponding figures for Ly-HE (25% and 98%, respectively). In contrast, the accuracy of Ly-IM was similar to that of Ly-HE in 83 cases of diffuse-type cancer. Conclusion Lymphatic vessels are most densely distributed in the MM layer in the gastric wall. Immunohistochemical identification of lymphatics is useful to increase the accuracy of diagnosing Ly in resected gastric EGCs. Ly-IM is superior to Ly-HE as a predictor of nodal metastasis, at least for intestinal-type EGC.     

食管癌术后复发转移的类型及预后分析

目的探讨食管癌术后复发转移的类型及影响生存的预后因素。方法对食管胸段鳞癌根治术后复发转移的１８５例进行回顾性分析。结果复发转移的中位生存时间为３０３天。复发转移类型：淋巴性转移１３７例,血行性转移１１例,混合型转移２９例,吻合口复发８例。本组半年及１,２,３,４年生存率分别为７０．０％、４７．１％、１９．８％、１２．２％和０％。多因素分析显示：肿瘤浸润深度、淋巴结转移、手术方式及不同治疗方案是影响生存率的预后因素。结论肿瘤浸润深度和淋巴结转移反映了肿瘤的生物学行为。提倡颈部吻合术,颈清扫术仅限于少数患者。放疗＋化疗可能延长复发转移患者的生存期,较有效的化疗方案有待进一步研究。     

High prevalence of peritoneal metastasis in gastric cancer presenting gastric outlet obstruction: A new candidate for consecutive diagnostic staging laparoscopy and laparoscopic gastrojejunostomy

IntroductionGastric cancer presenting gastric outlet obstruction (GC-GOO) is associated with two problems to be considered in its treatment: peritoneal metastasis and an inability to intake food. Because peritoneal metastasis is difficult to identify in standard examinations, laparoscopic gastrojejunostomy (LGJ), which consecutively follows diagnostic staging laparoscopy (DSL), may be a minimally invasive solution to these diagnostic and therapeutic problems. However, whether GC-GOO is a new candidate for DSL has been not evaluated.Materials and methodsGC-GOO patients who were surgically treated at our department between 2005 and 2014 were recruited. Patient backgrounds, preoperative and surgical findings for distant metastasis, and surgical curability were retrospectively evaluated. To predict peritoneal metastasis, the sensitivity, specificity, and positive and negative predictive values of preoperative factors were calculated. The survival outcomes were also evaluated according to surgical curability and non-curative factors.ResultsA total of 237 patients with GC-GOO were included in this study. Among them, 167 patients had no distant metastasis identified preoperatively. Seventy-one of 167 patients underwent curative surgery while 75 (44.9%) had peritoneal metastasis including positive lavage cytology. Ascites and large type 3 or type 4 tumors indicated high specificity (86.9% and 76.1%, respectively) and the involvement of gastric angle presented high sensitivity (90.7%) for peritoneal metastasis. The overall survival of patients with incurable surgery was worse than that of patients with curative surgery, regardless of their incurable factors.ConclusionGC-GOO is a new candidate for DSL. DSL followed by LGJ may be proposed, utilizing preoperative predictive factors for peritoneal metastasis.     

Applicability of the methylated CpG sites of paired box 5 (PAX5) promoter for prediction the prognosis of gastric cancer

Paired box gene 5 (PAX5), a member of the paired box gene family, is involved in control of organ development and tissue differentiation. In previous study, PAX5 promoter methylation was found in gastric cancer (GC) cells and tissues. At present study, we found that the inconsistently methylated levels of PAX5 promoter were identified in the different GC tissues. The methylated CpG site count and the methylated statuses of four CpG sites (-236, -183, -162, and -152) were significantly associated with the survival of 460 GC patients, respectively. Ultimately, the methylated CpG -236 was the optimal prognostic predictor of patients identified by using the Cox regression with AIC value calculation. These findings indicated that the methylated CpG -236 of PAX5 promoter has the potential applicability for clinical evaluation the prognosis of GC.     

淋巴管癌栓和淋巴结转移对胃癌术后生存率的影响

目的：探讨淋巴管癌栓与胃癌临床病理特点的关系。方法：比较淋巴管栓和淋巴结转移对胃癌预后的影响。结果：１）浸润深度及生长方式影响淋巴管癌栓的发生;２）只有在元淋巴结转移的条件下,淋这癌栓才会影响胃癌患者的预后。结论：淋巴结转移对一影响明显高于淋巴管癌栓。     

癌结节在胃癌患者预后中的价值

目的 探讨癌结节在胃癌根治术后患者预后中的价值。方法 收集2015年4月至2016年1月137例胃癌根治术的患者资料,分析癌结节状态与胃癌临床病理特征的关系,并随访患者1年无病生存率。结果 137例胃癌患者的癌结节阳性率为24.8％（34／137）。单因素分析发现,T／N分期越晚、神经／脉管浸润胃癌患者的癌结节阳性率越高。癌结节组与无癌结节组的1年无病生存率分别为59％和85％。对于Ⅰ／Ⅱ期患者,癌结节组和无癌结节组的1年无病生存率分别为40％和91％。结论 胃癌根治术后患者的癌结节与分期、神经／脉管浸润呈正相关。癌结节阳性提示胃癌术后高复发风险,其预后价值在Ⅰ／Ⅱ期胃癌中更显著。     

Outcome in relation to numbers of nodes harvested in lymph node-positive gastric cancer

Aims

We conducted a retrospective case–control study to compare the prognostic differences of lymph node-positive gastric cancer patients between dissected lymph nodes (DLNs) < 15 group and DLNs ≥ 15 group.

Methods

A retrospective study of 323 lymph node-positive gastric patients who underwent potentially curative resection for gastric cancer was analyzed to identify the prognostic differences between DLNs < 15 group and DLNs ≥ 15 group. Of these patients, 49 patients with <15 DLNs were matched with 147 patients with ≥15 DLNs according to gender, age, location of primary tumor, and type of gastrectomy.

Results

Patients with n1 lymph node metastasis (according to JCGC), serosal involvement, ratio of positive lymph nodes less than 25%, or without adjuvant chemotherapy in ≥15 DLN group had comparatively longer median survival than patients with homologous clinicopathologic variables in <15 DLN group, respectively. Patients with n1 stage lymph node metastasis, serosal involvement, non-intestinal Lauren classification, or without adjuvant chemotherapy in <15 DLN group had higher recurrence rate than patients with homologous clinicopathologic variables in ≥15 DLN group, respectively. In addition, we demonstrated that patients with more than n1 stage lymph node metastasis in <15 DLN group had higher rate of peritoneal dissemination than those with more than n1 lymph node metastasis in ≥15 DLN group.

Conclusions

DNL ≥15 was an important factor to improve the prognosis of lymph node-positive gastric cancer patients after potential curative resection.     

胃癌组织原钙黏蛋白10 mRNA表达水平与预后的相关性

背景与目的：编码原钙黏蛋白10(protocadherin-10,PCDH10)的PCDH10基因启动子甲基化与胃癌患者不良预后相关。但PCDH10表达水平与胃癌预后的关系不明确。该研究旨在分析PCDH10表达水平与胃癌预后及临床病理因素间的关系,寻找预测胃癌患者复发及死亡风险的指标。方法：采用实时荧光定量聚合酶链反应(real-time lfuorescent quantitative polymerase chain reaction,RTFQ-PCR)方法检测115对胃癌组织与相应癌旁组织PCDH10 mRNA的表达水平,分析PCDH10 mRNA的表达水平与预后及临床病理因素的关系。采用Logis-tic回归分析建立预测患者5年内复发或死亡风险的模型。结果：PCDH10 mRNA低表达组与非低表达组相比,无进展生存时间(progression-free survival,PFS)与总生存时间(overall survival,OS)显著延长(P值分别为0.046与0.033),淋巴结转移较少(P=0.001),TNM分期较早(P=0.001)。Cox单因素分析发现,Lauren分型、T分期、N分期、M分期及PCDH10 mRNA表达水平与PFS及OS显著相关。包含PCDH10作为参数的Logistic回归模型对胃癌患者术后5年内复发或死亡风险的预测效率与仅包含传统临床病理学参数的Logistic回归模型的预测效率相当。结论：PCDH10低表达胃癌患者淋巴结转移较少,TNM分期较早,预后较好,可以作为预测胃癌患者预后的辅助指标。基于PCDH10表达水平的Logistic回归模型可以在淋巴结转移情况不明时起到辅助判断患者预后的作用。     

Prognostic value of extracapsular invasion and fibrotic focus in single lymph node metastasis of gastric cancer

BACKGROUND: Histological findings of metastatic lymph nodes are important prognosticators in patients with gastric cancer. The aim of this study was to clarify the clinical significance of various pathological characteristics of the early phase of lymph node metastasis in patients with gastric cancer, by selecting patients with tumors that had single lymph node metastases, no serosal invasion, and no metastases to the peritoneum, liver, or distant organs. METHODS: Seventy-eight patients were eligible and were entered in this study. These patients were subdivided according to the following histological characteristics of the one metastatic lymph node: size of the metastasis (i.e., amount of tumor cells [AT]), proliferating pattern (PP), intranodal location (IL), and the presence or absence of extracapsular invasion (ECI) and/or fibrotic focus (FF). Associations between clinicopathological factors, survival, and the nodal findings were examined. RESULTS: There were no correlations between AT or PP and any clinicopathological factors. IL was significantly correlated with venous invasion and the pathological characteristics of the primary tumor. ECI and FF were observed significantly more frequently in pT2 than in pT1 cancer. Overall survival (OS) differed significantly according to depth of invasion, venous invasion, and the presence or absence of ECI or FF, although OS was not affected by AT, PP, or IL. The 10-year overall survival rates of patients with and without ECI were 50% and 80%, respectively, while these rates for patients with and without FF were 50% and 79%, respectively. Multivariate analysis revealed that ECI and FF were significant prognosticators of survival. CONCLUSION: These results strongly suggested that the presence of ECI or FF could affect the survival of patients with gastric cancer.     

Impact of pretreatment thrombocytosis on blood-borne metastasis and prognosis of gastric cancer

Background

Thrombocytosis has been associated with malignancies and poor prognostic implications in cancer patients. In the present study the prognostic significance of pretreatment platelet (PLT) level was assessed with regard to recurrence and survival in patients with primary gastric adenocarcinoma.

Methods

The authors reviewed the prospective data of 1593 gastric cancer patients who received curative gastrectomy with extended lymphadenectomy. The correlations of PLT level with recurrence and overall survival were evaluated by both univariate and multivariate analyses.

Results

Thrombocytosis (≥40 × 10⁴/μL), present in 6.4% of the patients prior to curative surgery, was more frequently associated with advanced T and N classification, larger tumor size, anemia, and leukocytosis (p < 0.05). In patients with pretreatment thrombocytosis compared to those without it, five-year survival rate was worse (56.9% vs. 65.5%; p = 0.043), and recurrence rate was higher mainly due to the frequent hematogenous spread (51.0% vs. 34.5%; p < 0.001). Furthermore, risk of blood-borne metastasis was almost three-fold higher in patients with pretreatment thrombocytosis (Odds ratio 2.83 [95% CI 1.67–4.77], p < 0.001).

Conclusions

Pretreatment thrombocytosis correlated significantly with poor prognosis and can be used as an independent predictor of recurrence by blood-borne metastasis in gastric cancer.