Inflammation-related markers and prognosis of alpha-fetoprotein producing gastric cancer

BACKGROUND Inflammation-related markers including neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR),monocyte-to-lymphocyte ratio(MLR),systemic immune-inflammation index(SII),systemic inflammation response index(SIRI)and prognostic nutritional index(PNI)could reflect tumor immune microenvironment and predict prognosis of cancers.However,it had not been explored in alpha-fetoprotein(AFP)producing gastric cancer(GC).AIM To determine the predictive value of inflammation-related peripheral blood markers including as NLR,PLR,MLR,SII,SIRI and PNI in the prognosis of AFPproducing GC(AFPGC).Besides,this study would also compare the differences in tumor immune microenvironment,clinical characteristics and prognosis between AFPGC and AFP-GC patients to improve the understanding of this disease.METHODS 573 patients enrolled were retrospectively studied.They were divided into AFP+group(AFP≥20 ng/mL)and AFP-group(AFP<20 ng/mL),comparing the levels of NLR/PLR/MLR/SII/SIRI/PNI and prognosis.In AFP+group,the impact of NLR/PLR/MLR/SII/SIRI/PNI and their dynamic changes on prognosis were further explored.RESULTS Compared with AFP-patients,AFP+patients had higher NLR/PLR/MLR/SII/-SIRI and lower PNI levels and poorer overall survival(OS).In the AFP+group,mortality was significantly lower in the lower NLR/PLR/MLR/SII/SIRI group and higher PNI group.Moreover,the dynamic increase(NLR/PLR/MLR/SII/-SIRI)or decrease(PNI)was associated with the rise of mortality within 1 year of follow-up.CONCLUSION Compared with AFP-patients,the level of inflammation-related peripheral blood markers significantly increased in AFP+patients,which was correlated with OS of AFP+patients.Also,the gradual increase of SII and SIRI was associated with the risk of death within one year in AFP+patients.AFPGC should be considered as a separate type and distinguished from AFP-GC because of the difference in tumor immune microenvironment.It requires basic experiments and large clinical samples in the future.

An isolate alpha-fetoprotein producing gastric cancer liver metastasis emerged in a patient previously affected by radiation induced liver disease

We report a case of an isolated hepatic neoplasia which originated in a site of the liver previously affected by radiation induced liver disease (RILD) in a patient resected for gastric cancer and referred to us for high serum alpha-fetoprotein (AFP) levels. This case challenged us in distiguishing, even histologically, between primary liver cancer and AFP producing gastric cancer metastasis. Only a panel of immunohis-tochemical markers allowed the definitive diagnosis of liver metastasis of endodermal stem cell-derived and AFP producing gastric cancer. We discuss the criteria for a differential diagnosis, as well as the possible link between RILD and emergence of liver neoplasia.

miR-122-5p as a novel biomarker for alpha-fetoproteinproducing gastric cancer

AIM To investigate the clinical utility of alpha-fetoprotein(AFP)-producing gastric cancer(AFPGC)-specific microRNA(mi RNA)for monitoring and prognostic prediction of patients.METHODS We performed a comprehensive miRNA array-based approach to compare miRNA expression levels between AFP-positive and AFP-negative cells in three patients with primary AFPGC.We next examined the expression levels of the selected miRNAs in five AFPGC and ten non-AFPGC tissue samples by quantitative reverse transcription-polymerase chain reaction to validate their utility.We also investigated the expression levels of the selected miRNA not only in tissue but also in plasma samples.Moreover,we investigated the relationship between plasma AFP levels and plasma selected miRNA expression levels,and also investigated the correlation of the selected miRNA expression levels and malignant potential.RESULTS Among the five miRNAs selected from the miRNA array results,the expression levels of miR-122-5p were significantly higher in the AFPGC patients than in the non-AFPGC patients(P<0.05).In tissue samples,mi R-122-5p expression level tended to be lower in the non-AFPGC tissue than the normal gastric mucosa.Conversely,in the AFPGC tissue,miR-122-5p expression level was significantly higher in the AFPGC tissue than both the normal gastric mucosa and the nonAFPGC tissue samples(P<0.05).Plasma mi R-122-5p expression levels were also significantly higher in the AFPGC patients than the health volunteers and the nonAFPGC patients(P<0.05)and were strongly correlated with plasma AFP levels(r=0.7975,P<0.0001).Moreover,the correlation of miR-122-5p expression in tissue samples with malignant potential was stronger than that of plasma AFP level in the AFPGC patients.In contrast,no correlation was found between mi R-122-5p expression levels and liver metastasis in the non-AFPGC patients.CONCLUSION miR-122-5p might be a useful biomarker for early detection and disease monitoring in AFPGC.

Clinicopathological features of alpha-fetoprotein producing early gastric cancer with enteroblastic differentiation

AIM To investigate clinicopathological features of early stage gastric cancer with enteroblastic differentiation(GCED).METHODS We retrospectively investigated data on 6 cases of early stage GCED and 186 cases of early stage conventional gastric cancer(CGC: well or moderately differentiated adenocarcinoma) who underwent endoscopic submucosal dissection or endoscopic mucosal resection from September 2011 to February 2015 in our hospital.GCED was defined as a tumor having a primitive intestine-like structure composed of cuboidal or columnar cells with clear cytoplasm and immunohistochemical positivity for either alpha-fetoprotein, Glypican 3 or SALL4. The following were compared between GCED and CGC: age, gender, location and size of tumor, macroscopic type, ulceration, depth of invasion, lymphatic and venous invasion, positive horizontal and vertical margin, curative resection rate.RESULTS Six cases(5 males, 1 female; mean age 75.7 years; 6 lesions) of early gastric cancer with a GCED component and 186 cases(139 males, 47 females; mean age 72.7 years; 209 lesions) of early stage CGC were investigated. Mean tumor diameters were similar but rates of submucosal invasion, lymphatic invasion, venous invasion, and non-curative resection were higher in GCED than CGC(66.6% vs 11.4%, 33.3% vs 2.3%, 66.6% vs 0.4%, 83.3% vs 11% respectively, P < 0.01). Deep submucosal invasion was not revealed endoscopically or by preoperative biopsy. Histologically, in GCED the superficial mucosal layer was covered with a CGC component. The GCED component tended to exist in the deeper part of the mucosa to the submucosa by lymphatic and/or venous invasion, without severe stromal reaction. In addition, Glypican 3 was the most sensitive marker for GCED(positivity, 83.3%), immunohistochemically.CONCLUSION Even in the early stage GCED has high malignant potential, and preoperative diagnosis is considered difficult. Endoscopists and pathologists should know the clinicopathological features of this highly malignant type of cancer.

Protein induced by vitamin K absence or antagonist Ⅱ-producing gastric cancer

Protein induced by vitamin K absence or antagonist Ⅱ(PIVKA-Ⅱ) is a putative specific marker of hepatocellular carcinoma(HCC),but it may also be produced by asmall number of gastric cancers.To date,16 cases of PIVKA-Ⅱ-producing gastric cancer have been reported,2 of which were reported by us and all of which were identified in Japan.There are no symptoms specific to PIVKA-Ⅱ-producing gastric cancer,and the representative clinical symptoms are general fatigue,appetite loss,and upper abdominal pain.Serum alpha-feto-protein(AFP)levels are also increased in almost allcases.Liver metastasis is observed in approximately 80% of cases and portal vein tumor thrombus is ob-served in approximately 20% of cases.Differential diagnosis between metastatic liver tumor and HCC is often difficult.Grossly,almost all cases appear as advanced gastric cancer.Histologically,a hepatoid pattern is observed in many cases,in addition to a moderately to poorly differentiated adenocarcinoma component.The production of PIVKA-Ⅱ and AFP is usually confirmed using immunohistochemical staining.Treatment and prognosis largely depends on the existence of liver meta-stasis,and the prognosis of patients with liver metas-tasis is very poor.PIVKA-Ⅱ may be produced during the hepatocellular metaplasia of the tumor cells.

Gastric adenosquamous carcinoma with an elevated serum level of alpha-fetoprotein:A case report

BACKGROUND Gastric adenosquamous carcinoma(ASC)is rare and characterized by coexisting of adenocarcinoma andsquamous carcinoma within the same tumor.We present a female patient with gastric ASC who had an elevated serum level of alpha-fetopro-tein(AFP),which decreased to normal levels after a laparoscopic distant radical gastrectomy in a short period.The clinicopathological features in AFP-producing gastric cancer(GC)are discussed,as well as potentially available prognostic predi-ctors.CASE SUMMARY A 50-year-old woman presented to our department with a chief complain of a 6-mo history of bloating.She had no basic diseases including heart diseases and respiratory diseases,and she also denied any prior history of dysphagia,hematemesis,melena,rectal bleeding,hematochezia,or unintentional weight loss.Based on her symptoms,an esophagogastroduodenoscopy was performed,showing an annular cavity lesion 3 cm from the pylorus with a diameter of 6 cm.A biopsy of the lesion showed gastric ASC,whereas the pylorus biopsy showed normal mucosa.The patient further received an enhanced computed tomography scan which demonstrated an invasive lesion close to the pylorus with a still clear margin of the tumor to peripheral organs such as the pancreas and liver.Scattered lymph nodes were visible around,whereas no sign of liver metastasis was discovered.Serum tumor markers including carcinoembryonic antigen(CEA),cancer antigen 199(CA199),CA724,CA125,and CA242 were all normal,while the level of serum AFP increased to 172 ng/mL.A laparoscopic distant radical gastrectomy was performed after exclusion of surgical contraindications.Postoperative pathology results showed that the tumor displayed an ulcerated ASC phenotype(90%of medium to highly-differentiated squamous cell carcinoma,10%of poorly differentiated adenocarcinoma.Surprisingly,the serum level of AFP decreased to normal level on post operation day 5.The tumor cells were positive for CK5/6,p63,and CEA,and negative for AFP and Epstein-Barr encoding region.CONCLUSION We presented a rare case of gastric ASC with elevated serum AFP level,which may be new subtype of AFP-producing GC.Follow-up detection of serum AFP might be a useful tool to predict patient prognosis.

Predictive and prognostic value of serum AFP level and its dynamic changes in advanced gastric cancer patients with elevated serum AFP

AIM To investigate predictive and prognostic value of serum alpha-fetoprotein(AFP) level and its dynamic changes in patients with advanced gastric cancer with elevated serum AFP(AFPAGC).METHODS One hundred and five patients with AFPAGC were enrolled in the study, and all of them underwent at least one cycle of systemic chemotherapy at our institute and had serum AFP ≥ 20 ng/m L at diagnosis or recurrence. Clinicopathologic features, serum AFP level at diagnosis and changes during treatment, first-line chemotherapy regimens, efficacy and toxicity, and survival information were collected. A Person's χ~2 or Fisher's exact test was used to measure the differences between variables. Survival prognostic factors were investigated using the Kaplan-Meier method and Cox regression.RESULTS Median serum AFP level was 161.7 ng/m L(range, 22.9-2557110 ng/m L). Objective response rates(ORR) was significantly lower in the AFP ≥ 160 ng/m L group than in the AFP < 160 ng/m L group(30.4% vs 68.3%, P < 0.001). ORR to doublet regimens was significantly lower in the AFP ≥ 160 ng/m L group, whereas ORR to triplet regimens was similar between the two groups. Liver metastasis rate was significantly higher in the AFP ≥ 160 ng/m L group than in the AFP < 160 ng/m L(69.8% vs 50.0%, P < 0.001). Overall survival(OS) in the two cohorts did not show any significant difference(P = 0.712). Dynamic changes of AFP were consistent with response to chemotherapy, and median OS of patients with a serum AFP decline ≥ 50% and those with a serum AFP decline < 50% was 17.5 m and 10.0 m, respectively(P = 0.003). Hepatic(P = 0.005), peritoneal(P < 0.001), non-regional lymph node metastasis(P < 0.001), and portal vein tumor thrombus(PVTT)(P = 0.042) were identified as independent prognostic factors for AFPAGC. CONCLUSION Real-time examination of AFP has great predictive and prognostic value for managing AFPAGC. For those with markedly elevated AFP, triplet regimens may be a better choice.

EPH-EPHRIN in human gastrointestinal cancers

Ever since its discovery two decades ago,the erythro- poietin-producing hepatoma (EPH)-EPHRIN system has been shown to play multifaceted roles in human gastroenterological cancer as well as neurodevelopment.Overexpression,amplif ication and point mutations have been found in many human cancers and many investigators have shown correlations between these up-regulationsand tumor angiogenesis.Thus,the genes in this family are considered to be potential targets of cancer therapy.On the other hand,the down-regulation of some members as a result of epigenetic changes has also been reported in some cancers.Furthermore,the correlation between altered expressions and clinical prognosis seems to be inconclusive.A huge amount of protein-protein interaction studies on the EPH-EPHRIN system have provided a basic scheme for signal transductions,especially bi-directional signaling involving EPH-ERPHRIN molecules at the cell membrane.This information also provides a manipulative strategy for harnessing the actions of these molecules.In this review,we summarize the known alterations of EPH-EPHRIN genes in human tumors of the esophagus,stomach,colorectum,liver and pancreas and present the perspective that the EPH-EPHRIN system could be a potential target of cancer therapy.

甲胎蛋白升高型胃癌的临床病理特征及预后分析

目的分析甲胎蛋白升高型胃癌(alpha-fetoprotein-producing gastric cancer,AFPGC)患者的临床病理特征和预后影响因素。方法回顾性分析2004年1月至2020年2月首都医科大学宣武医院收治的进行D2根治性手术治疗的531例胃癌患者的临床资料,选取所有AFPGC患者[甲胎蛋白(alpha fetoprotein,AFP)>30μg/L]为AFP升高胃癌组(22例),根据匹配原则另择同期首都医科大学宣武医院收治的22例AFP水平正常的胃癌患者为AFP正常胃癌组。比较分析两组患者的临床病理特征以及术后5年总生存率。分析影响AFPGC患者术后5年总生存率的独立危险因素。结果本研究中,AFPGC的比例为4.14%(22/531)。两组患者的肿瘤大小、肿瘤部位、肿瘤分化程度、肿瘤浸润深度、淋巴结转移、TNM分期比较差异均无显著性(P>0.05);AFP升高胃癌组患者的脉管浸润、同时性肝转移比例均显著高于AFP正常胃癌组(P<0.05)。Kaplan-Meier生存曲线显示,AFP升高胃癌组患者的术后5年总生存率显著低于AFP正常胃癌组(P<0.05)。单因素分析结果显示,AFPGC患者的术后5年总生存率与术前血清AFP水平、肿瘤分化程度、淋巴结转移、脉管浸润、同时性肝转移和TNM分期显著相关(P<0.05)。Cox多因素分析结果显示,术前血清AFP水平升高是影响AFPGC患者术后5年总生存率的独立危险因素(P<0.05)。结论AFPGC患者易发生脉管浸润和同时性肝转移,预后往往较差,且术前血清AFP水平升高是AFPGC患者预后不良的独立危险因素。

胃肝样腺癌:在摸索和争议中前进

胃肝样腺癌(hepatoid adenocarcinoma of stomach,HAS)是一种特殊类型的胃癌。其发病率不高,但由于HAS具有高度侵袭性的生物学行为,容易发生淋巴转移及肝转移,预后较差,受到临床广泛关注。随着HAS临床病理特征、预后以及分子生物学特征等的持续研究,关于HAS的认识正不断深入。然而,目前在HAS研究领域仍存在一些容易被忽视并亟需解决的问题。本文梳理既往关于HAS的病例报道及研究,在HAS的范畴、起源、诊断方法、分子生物学特征及预后等方面进行总结和探讨,以期为HAS的后续研究提供一定方向。

产甲胎蛋白型胃癌中甲胎蛋白表达的调控机制及其与肿瘤细胞恶性生物学行为的关系

目的探究产甲胎蛋白型胃癌(alpha-fetoprotein-producing gastric cancer,AFPGC)细胞中甲胎蛋白(alpha fetoprotein,AFP)表达的调控机制及其与肿瘤细胞恶性生物学行为的关系。方法使用人AFPGC细胞系FU97,采用亚克隆分选技术,建立18个亚克隆细胞株(M1~M18)。Western blot及荧光实时定量聚合酶链反应(real-time quantitative polymerase chain reaction,RT-qPCR)检测AFP表达,挑选出AFP表达最高和最低的2个亚克隆细胞株。通过划痕实验、上皮间质转化(epithelialmesenchymal transition,EMT)分子标志物检测、药物毒性实验及NSG小鼠皮下成瘤实验比较2个亚克隆细胞株的恶性生物学行为。应用RNA-seq检测FU97-AFP^(High)和FU97-AFP^(Low)细胞的差异表达基因,同时京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集分析关键信号通路改变,并使用Yes关联蛋白1(Yes-associated protein 1,YAP1)小分子抑制剂verteporfin干预实验进行验证。结果Western blot显示,FU97细胞不同亚克隆株AFP的表达水平差异大,亚克隆株M8和M12分别有最低和最高的AFP蛋白表达量。RT-qPCR显示,AFP高表达细胞株M12(FU97-AFP^(High))和AFP低表达细胞株M8(FU97-AFP^(Low))的AFP表达量分别为(38.70±3.37)和(3.33±0.04),差异具有统计学意义(P<0.01)。FU97-AFP^(High)细胞的迁移能力大于FU97-AFP^(Low)细胞(P<0.01),且高表达N-cadherin,低表达E-cadherin。细胞毒性实验表明,FU97-AFP^(High)细胞对5-氟尿嘧啶、多西他赛、顺铂和伊立替康的半抑制浓度(half maximal inhibitory concentration,IC50)分别为87.57、43.49、18.11和2.43μmol/L,均大于FU97-AFP^(Low)细胞,后者分别为77.19、38.14、16.76和0.94μmol/L。小鼠皮下成瘤实验显示,接种第40天时FU97-AFP^(High)细胞注射点形成皮下瘤,而FU97-AFP^(Low)注射点未见成瘤迹象。RNA-seq及富集分析显示,FU97-AFP^(High)细胞的磷酯酰肌醇3激酶(phosphatidylinositol 3 kinase,PI3K)-Akt、Hippo-YAP、Wnt和转化生长因子-β(transforming growth factor-beta,TGF-β)等信号通路存在上调。Verteporfin干预Hippo-YAP通路后FU97细胞的AFP转录水平(P<0.01)及蛋白表达量出现下调。结论AFPGC中细胞异质性显著,且AFP高表达与肿瘤细胞的恶性生物学行为有关。Hippo-YAP信号通路可能参与AFPGC中AFP的表达调控。

伴有肝样或肠母细胞分化胃腺癌的临床病理学观察

目的探讨伴有肝样或肠母细胞分化胃腺癌(GAHED)的临床病理学特征及诊断方法。方法收集7例GAHED,回顾性分析其临床特点、形态学表现及免疫表型,并进行相关文献复习。结果组织学上,所有肿瘤均由不同比例的管状、筛状、乳头状、实体和(或)小梁状生长模式构成,肿瘤细胞胞质透明或轻度嗜酸性,所有病例肿瘤细胞胞质可见嗜酸性小体。免疫组化方面,肿瘤细胞弥漫或局灶表达胚胎性或肝样分化标记物(SALL4、AFP、Glypican-3和Hepatocyte)中的一种或多种,其中Glypican-3是最敏感的标记物(阳性率100%)。5例p53呈突变型表达(阳性率71.4%)。7例患者均获得了临床随访资料,随访时间7~32个月,2例患者无瘤生存,2例伴瘤生存,3例死亡,其中2例伴有肝转移,1例伴有肝及其他脏器转移。结论GAHED不同于普通型胃腺癌,是一种罕见且高度侵袭性腺癌亚型,其组织学和免疫表型上都具有特征性的改变,临床和病理医生应熟知此特殊类型胃癌的临床和病理学特征,以便做出正确诊断和处理。

伴有肠母细胞分化的胃腺癌的临床病理观察

目的 研究具有肠母细胞分化的胃腺癌(GAED)的临床、病理学特点及诊断方法。方法 回顾性分析8例GAED的临床特点、形态学表现及免疫表型,并复习相关文献。结果 8例患者,男性6例、女性2例;年龄61~81岁;1例无明显症状,7例表现为消化道症状或贫血症状;肿瘤最大径为1. 2~7. 5 cm,大体以溃疡型为主,多位于胃的中下段;进展期胃癌者7例,早期胃癌者1例;伴淋巴结转移者6例;伴脉管癌栓者7例;伴神经侵犯者3例;伴肝转移者3例。镜下形态表现为具有显著透明胞质的胚胎性肠上皮分化特点。免疫组化:肿瘤细胞既不同程度表达肠型分化标记物CDX2和Mucin 2,又表达某些胚胎性分化标记物SALL4、AFP和Glypican 3,5例CCND1强阳性表达,6例TP53呈突变型表达。患者均行部分胃切除术,术后随访5~29个月,1例失访,2例死亡,5例疾病无进展生存。结论 GAED和普通型胃腺癌不同,是一种具有高度侵袭性的肿瘤,并表达肠型分化和胚胎型分化的分子标记物,其诊断和鉴别诊断应结合其特殊的形态学和免疫表型。

甲胎蛋白阳性胃癌的分子机制与诊疗现状

甲胎蛋白阳性胃癌(alpha-fetoprotein-producing gastric cancer,AFPGC)是一种特殊类型胃癌,与普通胃癌相比具有独特的分子机制和临床病理特征,因其转移率高、预后差、易误诊等特点近年来引起临床医师关注。近年来,血管内皮生长因子(vascular endothelial growth factor,VEGF)、人表皮生长因子受体2(human epidermal growth factor receptor 2,HER2)、细胞间质上皮转换因子(cellular-mesenchymal epithelial transition factor,c-Met)、婆罗双树样基因4(spalt-like transcription factor4,SALL4)和微RNA(micro RNA,miRNA)等分子在AFPGC中的过表达一定程度上揭示了相关信号通路和致癌分子与此类胃癌的关系,化学治疗药物和阿帕替尼、曲妥珠单抗等分子靶向药物也显示出了对AFPGC的疗效。

AFP阳性胃癌的研究现状及展望

胃癌是世界范围内威胁人类健康的重要疾病之一。在中国,胃癌的发病率和死亡率均居于前列。由于胃癌具有较强的异质性,因此其临床诊疗和基础研究都具有一定的难度。国际通行的胃癌分型方法主要有两类,一类是Lauren分型(肠型、弥漫型及混合型),另一类是WHO分型(乳头状腺癌、管状腺癌、黏液腺癌、低黏附性癌及肝样腺癌等)。因为AFP阳性胃癌具有独特的临床病理学特征,所以研究AFP阳性胃癌对于临床诊断、治疗以及随访复查,甚至对于肝癌的鉴别诊断均具有一定的现实意义。

产甲胎蛋白胃癌治疗及预后相关基因的研究进展

产甲胎蛋白胃癌(AFPGC)是一种特殊类型的胃癌,被认为是具有高度侵袭性的肿瘤,其恶性程度高,且极易发生转移,以至于对其治疗效果不佳、预后差。目前,治疗的手段以及监测的指标对该病效果有限,而VEGF、HER2、AFP、GPC3、SALL4相关基因与肿瘤发生、发展有着密切关系,如能合理地指导AFPGC的治疗与预后,将大大改善患者生活质量,延长患者生存期。本文将对产甲胎蛋白胃癌治疗及预后相关基因的研究进展作一综述。

提高对胃肝样腺癌和产甲胎蛋白胃癌的认识

胃癌中有两种大家认识较少的类型--胃肝样腺癌和产甲胎蛋白胃癌，这两种胃癌拥有独特的血清学、病理形态学、免疫组化和生物学行为特征。胃肝样腺癌是同时具有腺癌和肝细胞癌样分化特点的一种胃癌，大多数患者在血清和肿瘤组织中可检测出甲胎蛋白增高。产甲胎蛋白胃癌是指血清和肿瘤组织中甲胎蛋白呈阳性表达的胃癌，其肿瘤组织中相当一部分能观察到肝细胞癌样分化。

产甲胎蛋白胃癌和胃肝样腺癌

产甲胎蛋白胃癌（AFPGC）和胃肝样腺癌（HAS）是胃癌中较为特殊的2种类型，它们之间既有联系又有区别。临床上往往将AFPGC定义为血清AFP〉20ng／ml或者免疫组化AFP阳性的胃癌，HAS的诊断主要依靠病理形态学，即具有肝细胞癌分化形态特征的原发性胃癌。AFPGC和HAS的发病率均很低，尤其是HAS，为1％左右，均易发生肝转移和淋巴结转移，预后显著差于普通胃腺癌。随着高通量测序的开展，在胃癌分子分型逐渐明确的同时，人们对AFPGC和HAS的分子背景也有了一定的认识。目前，有效治疗仍是AFPGC和HAS的最大挑战，早期诊断和根治性手术切除可以很大程度地改善患者的预后，术后密切监测血清AFP水平和腹部影像学表现，有助于及早发现肝转移，而联合肝动脉介入化疗和射频消融等局部治疗可以改善患者的预后。靶向治疗在AFPGC和HAS治疗中有着广阔的前景。

“健脾益气生血法”对胃癌贫血患者细胞免疫功能的影响

[目的]观察"益气健脾生血法"代表方——归脾汤对胃癌贫血患者血红蛋白、红细胞计数、红细胞压积和外周血T细胞亚群变化的影响,并探究其临床意义。[方法]采用随机、对照、前瞻性临床研究方法,收集60例确诊为胃癌伴轻中度贫血的患者,分为试验组(基础营养支持联合归脾汤、力蜚能胶囊和叶酸片治疗)和对照组(基础营养支持联合力蜚能胶囊、叶酸片治疗)。28 d为1个疗程,治疗前后使用血液分析仪和流式细胞仪检测血红蛋白、红细胞计数、红细胞压积和外周血T细胞亚群水平变化,并进行2组间比较。[结果]与治疗前比较,2组胃癌贫血患者治疗后的血红蛋白、红细胞计数和红细胞压积均明显升高(P<0.05),且试验组升高水平较对照组更明显(P<0.05)。与治疗前比较,试验组治疗后的CD8 T细胞水平明显降低(P<0.05),CD3、CD4 T细胞水平、CD4/CD8比值、Th1、Tc1细胞水平以及Th1/Th2、Tc1/Tc2比值均明显升高(P<0.05),而对照组上述细胞水平变化均不大(P>0.05)。[结论]胃癌贫血患者细胞免疫功能低下,应用归脾汤辅助西医治疗可有效地纠正贫血,改善机体细胞免疫抑制状态,从而对胃癌综合治疗措施的实施产生积极作用。

甲胎蛋白阳性胃癌相关基因及治疗的研究进展

甲胎蛋白阳性胃癌（AFPGC）因拥有独特的基因学特征及临床特点,被认为是胃癌中的一种特殊类型。由于AFPGC淋巴结转移率及肝转移率均高于普通胃癌、预后差于普通胃癌的特点,引起学者们的广泛关注。VEGF、c-Met、GPC3、SALL4等被认为与肿瘤发生、发展和转移密切相关的基因,在AFPGC中均过表达。随着靶向药物的兴起,已有针对相关靶点的药物在相关领域取得了良好效果,值得关注的是,甲磺酸阿帕替尼片、苯甲磺酸索拉非尼片等靶向药物在治疗AFPGC患者中取得了令人满意的成果。现对AFPGC近年来相关基因及治疗的进展作一综述,为临床治疗AFPGC提供参考。