Subclassification of Stage IV Gastric Cancer (IVa,IVb, and IVc) and Prognostic Significance of Substages

Background  

Although the prognosis of stage IV gastric cancer is poor, some patients with stage IV gastric cancer had a long-term survival after gastrectomy. The objective of this study was to subclassify stage IV gastric cancer according to survival differences, evaluate the prognosis by substage, and identify the factors associated with patient survival in each substage.     

Detection and Prediction of Micrometastasis in the Lymph Nodes of Patients With pN0 Gastric Cancer

Background:The clinicopathologic significance of micrometastasis (MM) and tumor cell microinvolvement (TCM) in regional lymph nodes as identified by immunohistochemical staining for cytokeratin expression was evaluated in patients with node-negative gastric cancer.Methods:MM was defined as tumor cells with stromal reaction, and TCM was defined as individual tumor cells without stromal reaction. We investigated 1761 lymph nodes obtained from 67 gastric cancer patients whose diagnosis showed no lymph node metastasis by routine histological examination. The depth of tumor invasion was T1 (submucosa) in 33 patients and T2 (muscularis propria and subserosa) in 34 patients. The lymph nodes were examined immunohistochemically for the presence of tumor cells using anti-cytokeratin AE1/AE3 monoclonal antibody. Both the biopsy tumor specimens obtained prior to surgery and the resected primary tumors were immunostained with E-cadherin (E-cad) monoclonal antibody.Results:Thirty (1.5%) of the 1761 lymph nodes showed MM and/or TCM. MM with or without TCM was found in 10 patients, and TCM alone was found in 4 patients; 6 (18.2%) of the 33 patients with T1 tumor and 8 (23.5%) of the 34 patients with T2 tumor had occult lymph node metastasis. The 5-year survival rate was worse among those with MM with or without TCM, than among those without MM. Nearly all of the patients with MM and/or TCM had reduced or negative E-cad expression in the primary tumor.Conclusions:We demonstrated that the incidence of MM and/or TCM in the lymph nodes of patients with gastric cancer is quite high, and that such metastasis is associated with the prognosis of patients with pN0. Examination of E-cad expression in biopsy tumor specimens may be useful for predicting MM and/or TCM.     

Complications after Extended (D2) and Superextended (D3) Lymphadenectomy for Gastric Cancer: Analysis of Potential Risk Factors

BACKGROUND: Very few studies from Western centers have compared D2 and D3 dissection in the surgical treatment of gastric cancer. The aim of the prospective observational study reported here was to analyze the postoperative outcome and potential risk factors for complications following D2 and D3 lymphadenectomy. METHODS: A total of 330 consecutive patients, of which 251 submitted to D2 lymphadenectomy and 79 were treated by D3 lymphadenectomy, were enrolled in the study. Twenty potential risk factors for morbidity and mortality were studied by means of univariate and multivariate analysis. RESULTS: Overall morbidity and mortality rates were 34% (111 patients) and 4% (14 patients), respectively. Abdominal abscess, anastomotic leakage, pleuropulmonary diseases and pancreatitis were the most commonly observed complications. No differences in morbidity, surgical morbidity, mortality rates and mean hospital stay between D2 and D3 lymphadenectomy were found. Multivariate analysis revealed that American Society of Anesthesiologists' (ASA) class II/III versus class I, perioperative blood transfusions, and low albumin serum levels were independent predictors of postoperative complications. Age, surgical radicality (R1/R2 vs. R0) and low albumin serum levels independently predicted mortality. Mortality rate was .5% in the 203 patients aged 75 years or younger who underwent curative surgery. Most of deaths were observed in patients older than 75 years with low albumin serum levels or treated by non-curative surgery. CONCLUSIONS: D2 lymphadenectomy represents a feasible procedure associated to acceptable morbidity and mortality rates. In specialized centers, D3 lymphadenectomy may be performed without increasing the risk of postoperative complications and associated deaths in carefully selected patients. These techniques should be avoided in subgroups of patients with a high risk of postoperative mortality.     

Effects of postmastectomy radiotherapy on survival in different age groups for patients with T3N0M0 breast cancer

BackgroundPostmastectomy radiotherapy (PMRT), as an important regional treatment, improves the survival rate of patients with T3N0M0 breast cancers. However, the therapeutic effect of PMRT on T3N0M0 patients in different age groups is unclear.MethodsUsing Surveillance, Epidemiology, and End Results database, we identified 4840 T3N0M0 patients between 2000 and 2015. The primary and secondary outcomes were overall survival (OS) and breast cancer-specific survival (BCSS). Survival outcomes were compared using Kaplan-Meier survival test, COX regression analysis, propensity score matching and forest plot, which present the relationship between age and PMRT.ResultsSurvival analysis demonstrated that for young patients (aged 18–45 and 46–55), there was no significant difference in OS between with and without PMRT. However, for patients older than 65 years, PMRT could significantly improve survival time (P < 0.001). Multivariate Cox analysis of OS showed older patients with PMRT had a lower hazard ratio (HR) than those without PMRT (aged 56–65: HR = 0.67, P = 0.014; aged >65: HR = 0.60, P < 0.001), and little benefit for young patients. The consistent results were also observed in 1:1 matched cohort. Subgroup analysis revealed the survival HRs of with versus without PMRT for patients older than 65 years were significant in most subgroups.ConclusionThe effect of PMRT in T3N0M0 patients is related to the age. PMRT is associated with improved survival in older patients with T3N0M0 breast cancer, especially those older than 65 years. While the benefit of PMRT is limited in T3N0M0 patients of young age. The observation suggests the importance of age for T3N0M0 patients when individualized treatment is made.     

HG-1/IL-2基因修饰瘤苗治疗晚期胃癌的初步临床研究(附8例报告)

目的 :评估同种异型 (HLA A2 +)IL 2基因工程化人胃癌细胞瘤苗 (HG 1/IL 2 )治疗晚期胃癌的毒副作用及临床安全性。方法 :应用基因工程技术 ,以逆转录病毒载体介导将人IL 2cDNA转导入人胃癌细胞株MKN 45 ,经10 0Gy60Co照射灭活后 ,制备成基因工程化胃癌细胞瘤苗 (HG 1/IL 2 )。 2 0 0 1年 4月～ 2 0 0 1年 7月 ,对 8例晚期胃癌病人施行HG 1/IL 2瘤苗治疗。以 5次接种为一疗程 ,接种时间分别在第 1、8、15、2 9和第 5 8天 ,每次于一侧腹股沟和对侧腋部皮下多点注射 1× 10 7个细胞。每次接种后严格观察毒副反应 ,并在治疗开始前一周和治疗结束后进行临床评估 ,同时进行凝血功能、血液生化学、肿瘤标记物及相关免疫指标检测。结果 :除 1例在第 3次接种后 ,因高热和全身性荨麻疹而终止试验外 ,余均顺利完成治疗。接种后低热和注射局部红肿、酸胀感是最常见的反应。治疗前后未观察到病人血液学、凝血功能、肝肾功能、血清标志物等指标的明显异常。部分病人治疗后血清转铁蛋白、IgG、IgA、IgM、IL 2等体液免疫指标和CD3 、CD4 、CD8等细胞免疫指标有一定程度升高。结论 :在密切观察的前提下 ,HG 1/IL 2基因工程化胃癌细胞瘤苗应用于晚期胃癌的辅助治疗是安全可行的     

The Global Histone Modification Pattern Correlates with Cancer Recurrence and Overall Survival in Gastric Adenocarcinoma

Background  Epigenetic alterations such as DNA methylation and histone modification play important roles in carcinogenesis. It has been recently suggested that global histone modification patterns are independent predictors of cancer recurrence. In this study, we used immunohistochemistry to evaluate the patterns of histone H3 and H4 acetylation and trimethylation in gastric adenocarcinomas. Methods  Double 2-mm core tissue microarrays were made from 261 paraffin-embedded gastric adenocarcinoma samples and examined by immunohistochemistry for histone H3 lysine 9 (H3K9) acetylation and trimethylation, histone H4 lysine 16 acetylation, and histone H4 lysine 20 trimethylation. Sections were graded according to the proportion of tumor cells showing nuclear staining. Results  Trimethylation of H3K9 positively correlated with tumor stage (P = 0.043); lymphovascular invasion (P = 0.029), cancer recurrence (P = 0.043), and higher level of H3K9 trimethylation correlated with a poor survival rate (P = 0.008). Multivariate survival analysis showed that H3K9 trimethylation status is an independent prognostic factor (P = 0.014). After categorizing cases according to the dominant modification pattern, we found that methylation dominance was associated with lymphovascular invasion (P = 0.001), cancer recurrence (P = 0.001), and poor survival rate (P = 0.028). Methylation dominance was also an independent prognostic factor (P = 0.026) in multivariate survival analysis. Conclusion  The pattern of histone modification as detected by immunohistochemistry may be useful as a predictor for the recurrence of cancer and may be an independent prognostic factor in gastric adenocarcinomas.     

腹腔镜下残胃癌根治切除3例报告

目的 探讨腹腔镜残胃癌切除的可行性. 方法 全身麻醉,平卧两腿分开位,术者站患者左侧,五孔法操作.入腹后先分离胃肠道与腹壁的粘连.淋巴结清扫次序:No4、11、10、2、7、8a、9、1、3、15、14v.取上腹部5～7 cm小切口,移出残胃及吻合口两端部分空肠,直视下Roux-en-Y方式重建消化道. 结果 3例残胃癌成功在腹腔镜下完成根治性切除,手术时间分别为300、280、350 min,术中出血量分别为100、200、40 ml,清扫淋巴结数量分别为12、15、20枚.术后胃肠功能恢复时间4.5、5、5 d,进食时间5 d,下床活动时间5.5 d.无手术并发症.3例分别随访10、9、2个月,无复发. 结论 残胃癌不是腹腔镜手术禁忌证,在掌握腹腔镜D2根治技术的基础上可尝试开展.     

胃癌肿瘤干细胞在腹膜种植中的作用机理假说

目的 探讨肿瘤干细胞（CSC）在胃癌腹膜转移中可能的作用机理,并提出假说。方法 对CSC在胃癌腹膜种植转移中可能的作用机理进行综述,并提出系统性的理论假说。结果 肿瘤转移干细胞（MCSC）系具有转移特性的CSC亚群,但目前尚鲜有相关研究。MCSC转移是其趋向性迁移并定植到特定靶组织的多步骤“归巢”过程。胃癌腹膜转移是简化的“归巢”模式,可认为其关键环节是MCSC在腹膜的黏附、迁移和微环境的建立。捕获人胃癌腹膜转移灶的MCSC,并鉴定其干细胞性、高成瘤性及高侵袭性,是以MCSC为线索的胃癌腹膜转移机理研究的重要环节。结论 MCSC可能在胃癌腹膜种植的多环节过程中发生作用,但目前尚缺乏相关研究结果。     

The necessity of chemotherapy in T3N0M0 colon cancer without risk factors

Background

For patients with T3N0M0 colon cancer without known risk factors, the necessity of chemotherapy has no definite consensus.

Methods

From 1994 to 2004, we retrospectively analyzed 247 patients who had pathologically confirmed T3N0M0 colon cancer without risk factors.

Results

Among the 247 patients, 198 (80.2%) received chemotherapy and 49 (19.8%) underwent surgery alone. The 5-year survival rate was 92.8% for patients with T3N0M0 colon cancer without risk factors. Only chemotherapy increased survival (P = .032) by multivariate analysis. The 5-year survival rates were 85.4% in the surgery-only group and 94.2% in the group that received surgery with chemotherapy. There was no difference in the therapeutic efficacy of 5-fluorouracil, capecitabine, and uracil/tegafur (P = .424) for survival.

Conclusion

The results of this study showed that chemotherapy improved the survival of patients with T3N0M0 colon cancer without risk factors.     

Impact and Outcomes of Routine Microstaging of Sentinel Lymph Nodes in Breast Cancer: Significance of the pN0(i+) and pN1mi Categories

Background  In 2003, the American Joint Committee on Cancer (AJCC) initiated the 6th edition staging criteria, including pN0(i+) and pN1mi categories for breast cancer. However, the clinical significance of these categories is debated in the literature. Methods  A prospective registry was used to identify patients staged with sentinel lymph node (SLN) biopsy. SLN evaluation included routine serial sectioning and immunohistochemical stains. SLN biopsies performed before January 2003 were restaged according to the AJCC’s 6th edition criteria. Results  Of 954 SLN biopsies identified, on review, 491 N0i-, 86 N0i+, 73 N1mi, 146 N1a, 29 N2a, and 11 N3a patients were available for analysis with a median follow-up of 45.4 months. Significant prognostic and therapeutic differences existed between the groups. Differences in overall survival (OS) and recurrence-free survival (RFS) were only noted when the size of the metastases reached the N1a level. There were no statistically significant differences in OS or RFS between N0(i−) and N0(i+) or N1mi disease. Cases that were N0(i+) or N1mi were more likely to have other poor prognostic factors and to receive more aggressive therapy. Conclusion  SLN biopsy allows a more sensitive evaluation of lymph nodes for metastatic cells. This has led to the increased identification of very small axillary metastases. While the new microstaging categories are not yet clearly associated with a significantly decreased OS or DFS in this series, they are associated with other poor prognostic factors and more local/regional and systemic therapy. Further analysis of the microstaging categories is needed.     

遗传性非息肉病性结直肠癌家系中胃癌的特征和在家系遴选中价值

目的:探讨遗传性非息肉病性结直肠癌(HNPCC)家系中胃癌的临床特征和在HNPCC家系遴选中的价值。方法:回顾性随访了符合Amsterdam标准(Ⅱ)的6个HNPCC家系和2个胃癌聚集家系,将两组家系中的胃癌特征进行比较。结果:6个符合Amsterdam标准(Ⅱ)HNPCC家系中发现7例胃癌病人,年龄45～72岁。其中胃窦癌4例,胃体癌2例,贲门癌1例,生存时间6～18个月。2个不符合标准Ⅰ但符合标准Ⅱ的家系中,胃癌7例,其中贲门癌4例,胃窦癌2例,胃体癌1例;男性3例,女性4例,年龄45～77岁,生存时间9～37个月。两组病人的年龄、性别和生存时间差异无显著意义,但肿瘤部位差异有显著意义。结论:尽管在国内HNPCC家系中胃癌是主要的肠外肿瘤之一,由于难以与家族性胃癌鉴别,故胃癌不适合列入HNPCC家系的诊断标准。     

Adjustable Silicone Gastric Banding (ASGB): the Italian experience

Adjustable silicone gastric banding (ASGB) is a recently introduced gastric restrictive procedure. From April 1990 to April 1992, 85 patients underwent ASGB at our Department. Patients' characteristics were: 65 females, 20 males, mean age 39.6 years (range 17-60 years); body weight (BW) 127.9 ± 23 kg; % ideal body weight (%IBW) 205 ± 29; body mass index (BMI) 46 ± 7; morbidly obese 68, super-obese 17. Mean follow-up is 353 days. Twelve months after the operation BW was 95.2 ± 23 kg, % loss of excess BW 52.1 ± 22, and %IBW 152.2 ± 30 (45 patients). Mortality rate was zero and postoperative morbidity was insignificant. As late morbidity, we experienced two slippages of the band and six stoma-stenosis with pouch dilatation. Therefore, a surgical revision without removal of the band was performed in eight patients. The band was removed in one patient because of band erosion. In conclusion, ASGB is a safe and effective bariatric procedure. The weight loss is comparable to that produced by more extensive operations. Moreover, ASGB is fully reversible and adjustable to the patients' needs.     

Opa Interacting Protein 5 (OIP5) Is a Novel Cancer-testis Specific Gene in Gastric Cancer

Background Identification of novel cancer-specific antigens is important for the advancement of immunotherapy. Our aim was to identify cancer-specific genes in gastric cancer. Methods Using cDNA microarray analysis, we detected genes overexpressed specifically in gastric cancer cells. The expression levels of selected genes, including OIP5, was confirmed by real time RT-PCR analysis in tumor/normal paired bulk samples of 58 clinical cases. The expression levels of selected genes in normal tissues were also determined with a human total RNA master panel. We also compared the expression status of OIP5 with that of the other known cancer-testis specific genes. Results Twenty-two genes were determined to be upregulated in gastric cancer cells. Among these, three genes (CDC6, Exo1, and OIP5) were selected and confirmed to be upregulated in the tumor tissue compared to normal tissue. A human total RNA master panel demonstrated that OIP5, but not Exo1 or CDC6, showed high specificity in testis. Thus OIP5 may be considered a cancer-testis specific gene. In 58 clinical cases of gastric cancer examined, we found OIP5 gene expression in 27 cases (47%). Thirteen of these 27 cases showed no expression of the known cancer specific genes such as MAGE-1, MAGE-3 or NY-ESO-1. Conclusions Using a combination of LMD and microarray, we identified OIP5 as a cancer-testis specific gene. Further expression analysis in a set of clinical cases revealed that OIP5 may be a novel immunotherapy target for patients with gastric cancer. Grant sponsors: CREST, JST; Uehara Memorial Foundation; Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for Scientific Research, grant numbers 17015032, 17109013, 17591411, 17591413, and 16390381; Health and Labour Sciences Research Grants; Third Term Comprehensive Control Research for Cancer, 16271201.     

The Prognosis of T3N0 Colon Cancer Is Dependent on the Number of Lymph Nodes Examined

Background: T3N0 colon cancer is the target of many adjuvant studies. Very few studies have examined the relationship of the number of lymph nodes examined to the prognosis of this stage. We examined data from the National Cancer Data Base (NCDB) to determine whether the number of examined lymph nodes is prognostic for T3N0 colon cancer.Methods: A total of 35,787 prospectively collected cases of T3N0 colon cancer that were surgically treated and pathologically reported from 1985 to 1991 to the NCDB as T3N0M0 were analyzed.Results: The 5-year relative survival rate for T3N0M0 colon cancer varied from 64% if 1 or 2 lymph nodes were examined to 86% if >25 lymph nodes were examined. Three strata of lymph nodes (1–7, 8–12, and 13) distinguished significantly different observed 5-year survival rates.Conclusions: These results demonstrate that the prognosis of T3N0 colon cancer is dependent on the number of lymph nodes examined. A minimum of 13 lymph nodes should be examined to label a T3 colon cancer as node negative. These data suggest that adjuvant trials for T3N0 colon cancer should stratify according to the number of lymph nodes examined.Presented at the 54th Annual Meeting of the Society of Surgical Oncology, Washington, DC, March 17, 2001     

A Phase-II Clinical Trial of Laparoscopy-Assisted Distal Gastrectomy with D2 Lymph Node Dissection for Gastric Cancer Patients

Objectives This study was conducted to determine whether laparoscopy-assisted distal gastrectomy (LADG) with complete D2 lymph node dissection for gastric cancer is a safe and effective surgical option. Methods During an 8-month period, 64 patients, who were diagnosed preoperatively as having T1-2, N0-1 or M0 gastric cancer, were prospectively enrolled to undergo LADG with D2 lymph node dissection; two surgeons with experience of over 50 cases of laparoscopic gastrectomy performed the procedures. The compliance rate, defined as cases with no more than one missing lymph node station according to the Japanese Research Society of Gastric Cancer (JRSGC) lymph node grouping, for the open gastrectomy with D2 lymph node dissection was 66.0% in a pilot study and was used for calculations of sample size. Compliance rate and other surgical outcomes, including the number of retrieved lymph nodes from each lymph node station, morbidities, mortalities and conversion rate, were analyzed. Results The compliance rate was 67.2% and was similar to that of open distal gastrectomy reported in the pilot study. The mean number of retrieved lymph nodes was 50.1 (range 20–100). The most frequently missed lymph node station was no. 5 (31.2%) followed by no. 3 (25.0%). There were no missed lymph nodes at stations no. 6 and 9. The complication rate was 3.1% (2/66); there were two conversions (3.0%) and no mortalities. Conclusions The current study suggests that LADG with D2 lymph node dissection is oncologically feasible, and phase-III clinical trials will be needed.     

RhoA和Snail的表达与胃癌生物学行为的关系

目的检测RhoA和Snail在胃癌组织中的表达,以探讨它们与胃癌生物学行为的关系。方法采用免疫组织化学方法检测189例胃癌患者术后石蜡标本中RhoA和Snail蛋白的表达,分析它们的相关性以及与胃癌临床病理学特征和生存的关系。结果①RhoA和Snail在胃癌组织中的表达阳性率均分别明显高于其在癌旁组织（RhoA：P=0.008;Snail：P=0.000）和正常胃黏膜组织（RhoA：P=0.010;Snail：P=0.000）中的表达阳性率;RhoA在癌旁组织中的表达与其在正常胃黏膜组织中的表达差异无统计学意义（P=0.782）,而Snail在癌旁组织中的表达明显高于其在正常胃黏膜组织中的表达,差异有统计学意义（P=0.001）。②RhoA在胃癌组织中的阳性表达与胃癌的TNM分期和Lauren分型有关（P〈0.05）,而与胃癌的肿瘤直径、有无淋巴结转移及分化程度无关（P〉0.05）。Snail在胃癌组织中的阳性表达与胃癌肿瘤直径、有无淋巴结转移、分化程度、TNM分期及Lauren分型均有关（P〈0.05）。RhoA和Snail在胃癌组织中的阳性表达均与患者的性别和年龄无关（P〉0.05）。③胃癌组织中RhoA蛋白和Snail蛋白的表达呈显著正相关（rs=0.203,P=0.005）。④肿瘤TNM分期、RhoA及Snail表达和淋巴结转移均为胃癌术后患者的独立预后因素（P〈0.05）。结论 RhoA和Snail在胃癌组织中表达上调,它们可能共同参与了胃癌的发生、发展过程,且RhoA/Snail信号途径可能在胃癌的浸润和转移过程中发挥着重要作用。