腹腔热灌注化疗对不同病理类型和Borrmann分型进展期胃癌患者的预后分析

目的:回顾性分析行手术联合术后腹腔热灌注化疗(hyperthermic intraperitoneal chemotherapy,HIPEC)与同期单纯手术胃癌患者的临床病理资料,以期了解HIPEC对局部进展期胃癌患者预后的影响。方法:回顾性分析2009年1月~2014年1月在天津医科大学肿瘤医院行HIPEC的80例Ⅲb期胃癌患者与同期单纯手术90例Ⅲb期胃癌患者。根据术后是否使用腹腔热灌注化疗分为HIPEC组(研究组)和单纯手术组(对照组)。研究组:印戒细胞癌24例,非印戒细胞癌56例;BorrmannⅠ型12例,BorrmannⅡ型28例,BorrmannⅢ型23例,BorrmannⅣ型17例。对照组:印戒细胞癌26例,非印戒细胞癌64例;BorrmannⅠ型15例,BorrmannⅡ型30例,BorrmannⅢ型26例子,BorrmannⅣ型19例。两组患者术后4周均予以SOX方案化疗8个疗程。分析比较不同病理类型及Borrmann分型的胃癌患者术后生存情况,并对两组患者手术相关并发症进行对比。结果:研究组和对照组患者5年生存率分别为36.25%和28.89%(P<0.05);印戒细胞癌患者中,研究组和对照组患者5年生存率分别为25.00%和15.38%(P<0.05);非印戒细胞癌患者中,研究组和对照组患者5年生存率分别为41.07%和34.38%(P>0.05);BorrmannⅠ型胃癌患者中,研究组和对照组患者5年生存率分别为41.67%和40.00%(P>0.05);BorrmannⅡ型胃癌患者中,研究组和对照组患者5年生存率分别为35.71%和33.33%(P>0.05);BorrmannⅢ型胃癌患者中,研究组和对照组患者5年生存率分别为39.13%和26.92%(P<0.05);BorrmannⅣ型胃癌患者中,研究组和对照组患者5年生存率分别为29.41%和15.79%(P<0.05)。两组患者手术相关并发症的差异无统计学意义(P>0.05)。结论:手术联合HIPEC安全可行,有利于提高患有印戒细胞癌、BorrmannⅢ型及BorrmannⅣ型进展期胃癌患者术后的5年生存率,延长生存期。     

早期胃癌样5型进展期胃癌的形态及生物学特点

目的分析早期胃癌样5型进展期胃癌(5型胃癌)的临床及生物学特征。方法对手术确诊的398例胃癌中符合5型胃癌的17例患者,分析其内镜与大体标本形态学、组织病理学结果。结果17例5型胃癌占同期胃癌总数的4.3%,占进展期胃癌的5.3%,所有患者均行根治手术。形态学分类显示本组中Ⅱc型比例最高(8/17,47.0%),其次为Ⅱa Ⅱc型(7/17,41.2%)及Ⅱc Ⅲ型(2/17,11.8%),Ⅱa Ⅱc型在5型进展期胃癌中所占比例较早期胃癌中高(P<0.05)。该组中分化型癌8例,未分化型9例,与同期早期胃癌相比分化程度未见明显差异,女性患者分化程度较男性患者差(P<0.01)。5例患者(29.4%)伴淋巴结及周围脏器转移,转移发生率较同期早期胃癌为高。结论5型胃癌形态学及病理学特征均不同于传统意义的进展期癌与早期胃癌,内镜检查中仔细评估病灶蠕动及伸展性、超声内镜、钡餐及螺旋CT检查可能有助于鉴别5型进展期胃癌与早期胃癌,提高术前诊断准确性。     

Clinicopathologic study of patients with Borrmann type iv gastric carcinoma

Between 1979 and 1993, 665 Japanese patients with advanced gastric cancer underwent surgery at our hospital. These patients were divided into two groups, consisting of 102 patients with Borrmann type IV carcinoma, and the remaining 563 patients with all other types of gastric carcinoma, which were then compared clinicopathologically. In the patients with Borrmann type IV carcinoma, 77.4% of the lesions demonstrated poorly differentiated adenocarcinoma, and 99 patients were classified as Stage III or IV. The resection rate was 87.2% (89/102) with only 39 curative operations despite the fact that 70 total gastrectomies were performed. The incidence of peritoneal dissemination (29.4%) and serosal invasion (97.0%) was significantly higher in these patients. Microscopic lymph node metastasis was positive in 86.5%. The 5-year survival rate was 23.4% in the patients with a curative operation and 5.0% in those with a noncurative operation (p < 0.01). Peritoneal dissemination was most frequently noted in the recurrence patterns. We conclude that early detection and a curative operation are both essential to improve the prognosis of patients with Borrmann type IV gastric cancer. The addition of a potent postoperative chemotherapy regimen is also recommended. © 1995 Wiley-Liss, Inc.     

Clinical impact of MMP and TIMP gene polymorphisms in gastric cancer

Gastric cancers express enhanced levels of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). Single-nucleotide polymorphisms (SNPs) in MMP and TIMP genes may be associated with disease susceptibility and might also affect their antigen expression. We studied the genotype distribution and allele frequencies of SNPs of MMP-2, -7, -8 and -9 and TIMP-1 and -2 in gastric cancer patients in relation to tumour progression, patient survival and tissue antigen expression. The genotype distribution and allele frequencies were similar in gastric cancer patients and controls, except for MMP-7(-181A>G). In addition, the genotype distribution of MMP-7(-181A>G) was associated with Helicobacter pylori status (chi(2) 7.8, P=0.005) and tumour-related survival of the patients. Single-nucleotide polymorphism TIMP-2(303C>T) correlated significantly with the WHO classification (chi(2) 5.9, P=0.03) and also strongly with tumour-related survival (log rank 11.74, P=0.0006). Single-nucleotide polymorphisms of MMP-2, -8, -9 and TIMP-1 were not associated with tumour-related survival. Only the gene promoter MMP-2(-1306C>T) polymorphism correlated significantly with the protein level within the tumours. First-order dendrogram cluster analysis combined with Cox analysis identified the MMP-7(-181A>G) and TIMP-2(303C>T) polymorphism combination to have a major impact on patients survival outcome. We conclude that MMP-related SNPs, especially MMP-7(-181A>G) and TIMP-2(303C>T), may be helpful in identifying gastric cancer patients with a poor clinical outcome.     

基于COX回归研究Borrmann Ⅳ型胃癌的预后因素

目的探讨影响Borrmann Ⅳ型胃癌预后的相关因素,寻找改善其预后的方法。 方法回顾性分析2000年1月至2010年12月中山大学肿瘤防治中心收治的有完整随访资料的Borrmann Ⅳ型胃癌220例。选择年龄（X₁）、性别（X₂）、腹水（X₃）、肿瘤波及范围（X₄）、肿瘤大小（X₅）、手术方式（X₆）、分化程度（X₇）、术后病理分期（pTNM）（X₈）、综合治疗（X₉）共9项临床病理参数作为观察指标。Kaplan-Meier法计算中位生存时间和生存率,影响生存率的单因素分析用Log-rank检验,Cox回归风险比例模型行多因素预后分析。 结果生存分析显示,全组患者的中位生存期288 d,1、3、5年生存率分别为47.1%、14.3%、9.1%。单因素分析表明,年龄、有无腹水、肿瘤波及范围、肿瘤大小、手术方式、pTNM分期均为Borrmann Ⅳ型胃癌预后的影响因素,COX回归多因素分析发现,手术方式、pTNM分期是影响Borrmann Ⅳ型胃癌预后的独立因素（P<0.05）。 结论提高Borrmann Ⅳ型胃癌的早期诊断水平及手术切除率有利于改善预后。     

Carcinoembryonic antigen (CEA) in stage IV gastric cancer as a risk factor for liver metastasis: A univariate and multivariate analysis

Serum carcinoembryonic antigen (CEA) levels were determined in 68 patients with Stage IV gastric cancers, the objective being to examine the clinicopathological relationship between the metastatic patterns of gastric cancer and the serum CEA level. Of the 68 patients, 31 were diagnosed as cases of liver metastases and 37 as cases of peritoneal dissemination. Serum CEA levels were elevated in 21 of 31 patients (67.8%) with liver metastases and in 7 of 37 patients (18.9%) with peritoneal dissemination (P < 0.01). A univariate analysis showed that liver metastasis correlated with a young age (P < 0.01), the lower portion of stomach (P < 0.05), Borrmann types 1 and 2 (P < 0.01), differentiated type (P < 0.01), and nonserosal involvement (P < 0.05) more than did peritoneal dissemination. A multivariate analysis showed that in addition to Borrmann type 1 and 2, elevated CEA levels (>2.5 ng/ml) is an independent risk factor involved in liver metastasis. Thus careful follow-up and postoperative adjuvant therapy are required for patients with elevated CEA levels, even with “curative” resection. © 1993 Wiley-Liss, Inc.     

Causation of Borrmann type 4 gastric cancer: heritable factors or environmental factors?

Background: The prognosis of Borrmann type 4 gastric cancer remains poor today. The relative contributions of genetic factors and nongenetic factors to type 4 gastric cancer are unclear. The study of family history and spousal history of cancer may play an important role in the assessment of causation of this severe gastric cancer. Methods: During the period 1995–1997, 1118 consecutive patients with histologically confirmed gastric cancer (probands), including 113 with type 4 carcinoma, were admitted to the National Cancer Center Hospital. The type of carcinoma, as well as the family history of cancer in first-degree relatives and spouses of the probands, was abstracted from medical records. Family history and spousal history of cancer were compared between type 4 and other types of gastric cancer. Results: While paternal history had no association with type 4 carcinoma compared with other types, maternal history was associated with a fourfold risk [95% confidence interval (CI), 1.6–9.3] of daughters' type 4 carcinoma, but not sons'. Among probands whose wives had a history of gastric cancer, the risks of type 4 gastric cancer were significantly increased, to as high as 13-fold (95% CI, 2.5–65.3). However, husbands' history had no relationship with wives' type 4 carcinoma. No relationship between type 4 carcinoma and family history or spousal history of other cancers was observed. Conclusion: The present study suggested that environmental factors may have a key effect in causing type 4 carcinoma. The findings may be valuable for identifying subjects at high risk of such malignant gastric cancer as Borrmann type 4. Received: June 3, 2002 / Accepted: September 19, 2002 Acknowledgments The authors thank Dr. S. Yamamoto for providing useful advice on design. This work was supported by a Grant-in-Aid for Cancer Research and for the Second-term Comprehensive 10-Year Strategy of Cancer Control from the Ministry of Health and Welfare, and a grant from the Ministry of Education, Culture, Sports, Science, and Technology of Japan. Dr. Y. Liu is an Awardee of a Research Resident Fellowship from the Foundation for Promotion of Cancer Research, Japan. Offprint requests to: Y. Liu     

K-ras mutation influences macroscopic features of gastric carcinoma

INTRODUCTION: Gastric carcinoma is classified morphologically as type 1 to 4. Type 1 is defined as a polypoid tumor; types 2 and 3 are defined as ulcerated tumors with polypoid growth or gastric wall infiltration, respectively, and type 4 tumors are defined as flat. This morphological classification is important because biological characteristics differ between the four morphological types, but little is known about genetic differences between them. MATERIALS AND METHODS: One hundred eight gastric tumors were classified macroscopically as type 1 to 4. Tumoral DNA was microdissected from paraffin-embedded tissue sections. PCR amplification of exon 1 of a K-ras containing codons 12 and 13 was performed. K-ras amplicons were dot-blotted onto nylon filters and hybridized with radiolabeled oligomer primers. RESULTS: A K-ras mutation was found in 20 of 108 gastric cancers. A significant relationship of K-ras mutation with polypoid cancer was found. The frequency of K-ras mutation was 6/14 (43%), 8/29 (28%), 2/11 (18%), and 4/54 (7%) in type 1 to 4 tumors, respectively. K-ras mutation was correlated with well-differentiated tumors. Of various types of K-ras mutations, 12 Asp often was seen in type 1 and 2 gastric cancers (well-demarcated, elevated tumors), while 12 Val and 12 Ser were often seen in type 3 and 4 cases (infiltrating carcinomas). CONCLUSION: K-ras mutations occur prominently in type 1 and type 2 gastric cancers.