舒芬太尼联合右美托咪定对胃癌/结直肠癌根治患者术后镇痛及呼吸的影响

目的研究舒芬太尼联合右美托咪定对胃癌/结直肠癌根治术患者术后镇痛效应及呼吸抑制的影响。方法将2018年8月—2020年8月收治的80例择期拟行胃癌/结直肠癌根治术治疗患者纳入研究。以随机数字表法将其分作观察组及对照组,每组各40例。对照组镇痛药物选用舒芬太尼,观察组镇痛药物的选用是在对照组的基础增用右美托咪定。分析两组镇痛、镇静效果,平均动脉压(MAP)以及血氧饱和度(SpO_(2))情况,不良反应,术后24 h舒芬太尼用量、经静脉患者自控镇痛(patient controlled intravenous analgesia,PCIA)用药量、追加镇痛药次数以及镇痛泵按压次数等方面的差异。结果两组视觉模拟评分法(VAS)及Ramsay评分在入室时比较,差异无统计学意义(P>0.05)。而在术后12、24、36、48 h时对比,观察组VAS评分相较于对照组更低,而Ramsay评分相较于对照组更高,差异有统计学意义(P<0.05)。两组入室时的MAP及SpO_(2)对比,差异无统计学意义(P>0.05)。而在术后12、24、36、48 h时对比,观察组MAP相较于对照组更低,差异有统计学意义(P<0.05)。在恶心呕吐发生率方面对比,观察组低于对照组,差异有统计学意义(P<0.05)。两组均无呼吸抑制的状况发生。两组的寒战、皮肤瘙痒、心动过缓、头晕的发生率差异无统计学意义(P>0.05)。观察组术后24 h舒芬太尼用量、PCIA用药量、追加镇痛药次数以及镇痛泵按压次数均低于对照组(均P<0.05)。结论舒芬太尼联合右美托咪定对胃癌/结直肠癌根治术患者的术后镇痛效应较佳,且不会引起呼吸抑制,可减少镇痛药物的应用以及镇痛泵按压次数。

胃癌转移结肠癌的危险因素及其与组织学类型的相关性

目的通过回顾性分析胃癌患者的临床资料,对胃癌转移结肠癌的危险因素及其组织学类型相关性进行研究,为早期诊治胃癌转移结肠癌提供有力依据。方法选取2013年1月至2015年11月我院肿瘤科收治的132例胃癌患者为研究对象,依据是否有结肠癌转移分为观察组和对照组,两组均行胃癌根治术。通过一般资料和病历整理以及术后病理学组织研究,分析性别、年龄、胃癌病灶部位、病灶大小、病理组织学类型、浸润深度、淋巴结转移情况与胃癌转移结肠癌间的关系。结果通过临床观察和严格诊断,两组单因素分析结果显示,胃癌转移结肠癌与性别、年龄无关(P>0.05),与胃癌病灶部位、病灶大小、浸润深度、淋巴结转移情况密切相关(P<0.05),其中病灶部位在胃窦(51.28%)、胃底体贲门处(66.67%)、病灶大小≥5 cm者(64.10%)、浸润深度在浆膜内(T1-2)处(72.22%)、淋巴结转移数目>6个(64.10%)更易发结肠癌转移。胃癌术后病理组织学检查发现胃癌转移结肠癌危险因素与组织学类型(高分化腺癌、中分化腺癌、低分化腺癌、黏液腺癌、印戒细胞癌)密切相关(P<0.05),其中低分化腺癌39.74%、黏液腺癌20.51%、印戒细胞癌32.05%与高、中分化腺癌比更易发生转移(P<0.05)。结论胃癌转移结肠癌的危险因素有胃癌病灶部位、病灶大小、病理组织学类型、浸润深度、淋巴结转移,且病灶部位在胃窦、胃底体贲门处、病灶大小≥5 cm者、浸润深度在浆膜内(T1-2)处、淋巴结转移数目>6个、组织学类型为低分化腺癌、黏液腺癌、印戒细胞癌者更易发生结肠癌转移。

胃肠道癌肿患者外周血CD4^＋CD25^＋FOXP3^＋调节性T细胞的表达及临床意义

目的：研究胃肠道癌肿患者外周血CD4^＋CD25^＋FOXP3^＋调节性T（Treg）细胞的表达，并探讨其临床意义。方法：通过免疫荧光术及流式细胞仪检测20例胃癌患者及20例结肠癌患者外周血CD4^＋CD25^＋FOXP3^＋Treg细胞、CD4^＋CD25^＋high Treg细胞、CD4^＋T细胞及CD4^＋ CTLA-4^＋T细胞。结果：胃癌组、结肠癌组与健康献血者比较外周血CD4^＋CD25^＋FOXP3^＋ Treg细胞、CD4^＋CD25^＋high Treg细胞及CD4^＋CTLA-4^＋T细胞显著增多，CD4^＋T细胞显著减少；胃癌、结肠癌患者之间其外周血中CD4^＋CD25^＋FOXP3^＋Treg细胞、CD4^＋CD25^＋high Treg细胞、CD4^＋T细胞及CD4^＋CTLA-4^＋T细胞无显著差异。结论：胃肠道癌肿患者外周血CD4^＋CD25^＋FOXP3^＋Treg细胞显著高于健康献血者，这可能与胃肠道癌肿患者的免疫抑制和肿瘤的进展相关。

Rac1小干扰RNA对胃肠道肿瘤细胞恶性生物学行为的影响

目的观察Rac1小干扰RNA(Rac1 siRNA)对胃肠道肿瘤细胞增殖、迁移、侵袭和凋亡的影响。方法Rac1 siRNA在lipofectamineTM2000介导下转染胃癌SGC803细胞和结直肠癌Lovo细胞,转染48h后,采用半定量RT-PCR和Western blot技术分别检测Rac1mRNA及蛋白的表达;Cell Counting Kit-8检测Rac1siRNA转染细胞的增殖变化;损伤刮擦实验和体外侵袭实验(Transwell小室)分别检测转染细胞株的迁移与侵袭能力;用流式细胞仪检测转染细胞株的凋亡。结果成功转染Rac1 siRNA的肿瘤细胞,RT-PCR及Western blot显示Rac1 mRNA和蛋白表达在相应的肿瘤细胞中都明显下降;Rac1 siRNA对肿瘤细胞的增殖、迁移和侵袭均有显著的抑制作用并能促进肿瘤细胞的凋亡。结论Rac1与胃肠道肿瘤细胞的恶性生物学行为密切相关。Rac1 siRNA能够部分逆转胃癌细胞SGC803和肠癌细胞Lovo的恶性生物学行为。

组蛋白去乙酰化酶及去甲基化酶抑制剂在胃肠道肿瘤的研究进展

组蛋白甲基化及乙酰化修饰的平衡失调与多种肿瘤的发生、发展、侵袭、转移密切相关,多种胃肠道肿瘤中发现组蛋白去乙酰化酶(HDAC)及组蛋白赖氨酸特异性去甲基酶1(LSD1)异常增高。相应的,一些组蛋白去乙酰化酶抑制剂(HDACi)和LSD1抑制剂已在胃肠道肿瘤的研究中取得进展,如异羟肟酸类HDACi在胃肠道抗肿瘤研究中取得良好疗效,但因其特异选择性低,易产生耐药性和严重副作用,在临床的进一步研究中受到限制;苯甲酰胺类HDACi在特异选择性有所提高,并且能够通过抑制肿瘤细胞分化、诱导免疫自噬、抑制细胞周期蛋白产生抑瘤作用,但其由于活性低而受到限制;环肽类HDACi特异性进一步增加,但只是出于研究的基础阶段。相应的,LSD1抑制剂,如苯环丙胺类、多肽类、小分子化合物抑制剂均在细胞层面有着良好的抑瘤作用,也在后期的整体实验均显示出耐药性和严重副作用。这提示着单一的HDACi和LSD1抑制剂的抑瘤效应均不佳,由于HDAC常和LSD1形成复合体发挥转录调节作用,因此,双靶点抑制剂可能是有效的,后期的双靶点抑制剂,比如Duan YC等人报道了TCP和SAHA的组合产生的环戊二烯衍生物,Anastas JN报道的Corin,的确呈现出更加显著的抑瘤成效,本文就HDAC、LSD1抑制剂及二者的双重抑制剂在胃肠道肿瘤的研究进展进行综述。

Detection of RASSF1A promoter hypermethylation in serum from gastric and colorectal adenocarcinoma patients

AIM：To evaluate the diagnostic role of serum RASSF1A promoter hypermethylation in gastric and colorectal adenocarcinoma. METHODS：Methylation-specific polymerase chain reaction （MSPCR） was used to examine the promoter methylation status of the serum RASSF1A gene in 47 gastric adenocarcinoma patients, 45 colorectal adenocarcinoma patients, 60 patients with benign gastrointestinal disease （30 with benign gastric disease and 30 with benign colorectal disease）, and 30 healthy donor controls. Apaired study of RASSF1A promoter methylation status in primary tumor, adjacent normal tissue, and postopertive serum were conducted in 25 gastric and colorectal adenocarcinoma patients who later were underwent surgical therapy. RESULTS：The frequencies of detection of serum RASSF1A promoter hypermethylation in gastric （34.0%） and colorectal （28.9%） adenocarcinoma patients were significantly higher than those in patients with benign gastric （3.3%） or colorectal （6.7%） disease or in healthy donors （0%） （P 〈 0.01）. The methylation status of RASSF1A promoter in serum samples was consistent with that in paired primary tumors, and the MSPCR results for RASSF1A promoter methylation status in paired preoperative samples were consistent with those in postoperative serum samples. The serum RASSF1A promoter hypermethylation did not correlate with patient sex, age, tumor differentiation grade, surgical therapy, or serum carcinoembryonic antigen level. Although the serum RASSF1A promoter hypermethylation frequency tended to be higher in patients with distant metastases, there was no correlation between methylation status and metastasis. CONCLUSION：Aberrant CpG island methylation within the promoter region of RASSF1A is a promising biomarker for gastric and colorectal cancer.

Relationship between nm23H1 genetic instability and clinical pathological characteristics in Chinese digestive system cancer patients

AIM: To study the relationship between nm23H1 gene genetic instability and its clinical pathological characteristics in Chinese digestive system cancer patients. METHODS: Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) was used to analyze the microsatellite instability (MSI) and loss of heterozygosity (LOH). Immunohistochemistry was employed to detect the expression of nm23H1. RESULTS: The MSI was higher in TNM stageⅠ + Ⅱ than in stage Ⅲ + Ⅳ of gastric, colonic and gallbladder carcinomas. The LOH was higher in TNM stage Ⅲ + Ⅳ than in stageⅠ + Ⅱ of gastric, colonic and hepatocellular carcinomas. Lymphatic metastasis was also observed. The expression of nm23H1 protein was lower in TNM stage Ⅲ + Ⅳ than in stageⅠ + Ⅱ of these tumors and in patients with lymphatic metastasis.The nm23H1 protein expression was higher in the LOH negative group than in the LOH positive group.CONCLUSION: MSI and LOH may independently control the biological behaviors of digestive system cancers. MSI could serve as an early biological marker of digestive system cancers. Enhanced expression of nm23H1 protein could efficiently inhibit cancer metastasis and improve its prognosis. LOH mostly appears in late digestive system cancer.

Endoscopic submucosal dissection for gastrointestinal neoplasms

Endoscopic submucosal dissection (ESD) is an advanced technique of therapeutic endoscopy for superficial gastrointestinal neoplasms. Three steps characterize it:injecting fluid into the submucosa to elevate the lesion, cutting the surrounding mucosa of the lesion, and dissecting the submucosa beneath the lesion. The ESD technique has rapidly permeated in Japan for treatment of early gastric cancer, due to its excellent results of en- bloc resection compared to endoscopic mucosal resection (EMR). Although there is still room for improvement to lessen its technical difficulty, ESD has recently been applied to esophageal and colorectal neoplasms. Favorable short-term results have been reported, but the application of ESD should be well considered by three aspects:(1) the possibility of nodal metastases of the lesion, (2) technical difficulty such as location, ulceration and operator’s skill, and (3) organ characteristics.

Gastric cancer patients at high-risk of having synchronous cancer

AIM： To identify patients with a high-risk of having a synchronous cancer among gastric cancer patients. METHODS： We retrospectively analyzed the prospective gastric cancer database at the National Cancer Center, Korea from December 2000 to December 2004. The clinicopathological characteristics of patients with synchronous cancers and those of patients without synchronous cancers were compared. Multivariate analysis was performed to identify the risk factors for the presence of a synchronous cancer in gastric cancer patients. RESULTS： 111 of 3291 gastric cancer patients （3.4%） registered in the database had a synchronous cancer. Among these 111 patients, 109 had a single synchronous cancer and 2 patients had two synchronous cancers. The most common form of synchronous cancer was colorectal cancer （42 patients, 37.2%） followed by lung cancer （21 patients, 18.6%）. Multivariate analyses revealed that elderly patients with differentiated early gastric cancer have a higher probability of a synchronous cancer. CONCLUSION： Synchronous cancers in gastric cancer patients are not infrequent. The physicians should try to find synchronous cancers in gastric cancer patients, especially in the elderly with a differentiated early gastric

HER2 aberrations and heterogeneity in cancers of the digestive system: Implications for pathologists and gastroenterologists

Management of cancers of the digestive system has progressed rapidly into the molecular era. Despite the significant recent achievements in the diagnosis and treatment of these patients, the number of deaths for these tumors has currently plateaued. Many investigations have assessed the role of HER2 in tumors of the digestive system in both prognostic and therapeutic settings, with heterogeneous results. Novel testing and treatment guidelines are emerging, in particular in gastric and colorectal cancers. However, further advances are needed. In this review we provide a comprehensive overview of the current state-ofknowledge of HER2 alterations in the most common tumors of the digestive system and discuss the operational implications of HER2 testing.

Forgotten node:A case report

Sister Mary Joseph nodule or node refers to a palpable nodule bulging into the umbilicus and is usually a result of a malignant cancer in the pelvis or abdomen.Traditionally it has been considered a sign of ominous prognosis.Gastrointestinal malignancies,most commonly gastric,colon and pancreatic cancer account for about 52% of the underlying sources.Gynecological cancers,most commonly ovarian and uterine cancers account for about 28% of the sources.

Comparative study of CEA and CA19-9 in esophageal,gastric and colon cancers individually and in combination(ROC curve analysis)

Objective： To determine the clinical serum levels of carcinoembryonic antigen （CEA） and carbohydrate antigen 19-9 （CA19-9）, individually and in combination, for the diagnosis of 50 healthy subjects and 150 cases of esophageal, gastric, and colon cancers. Methods： The sensitivities of the two markers were compared individually and in combination, with specificity set at 100%. Receiver operating characteristic （ROC） curves were plotted. Results： Serum CEA levels were significantly higher in cancer patients than in the control group. The sensitivity of CEA was determined： in esophageal cancer, sensitivity=28%, negative predictive value （NPV）=61.72%, and AUC=0.742 （SE=0.05）, with a significance level of P〈0.0001; in gastric cancer, sensitivity=30%, NPV=58.82%, and AUC=0.734 （SE=0.0S）, with a significance level of P〈0.0001; in colon cancer, sensitivity=74%, NPV=79.36%, and AUC=0.856 （SE=0.04）, with a significance level of P〈0.0001. The sensitivity of CA19-9 was also evaluated： in esophageal cancer, sensitivity=18%, NPV=54.94%, and AUC=0.573 （SE=0.05）, with a significance level of P=0.2054. In gastric cancer, sensitivity=42%, NPV=63.29%, and AUC=0.679 （SE=0.05）, with a significance level of P〈0.0011. In colon cancer, sensitivity=26%, NPV=57.47%, and AUC=0.S80 （SE=0.05）, with a significance level ofP=0.1670. The following were the sensitivities of CEA/CA19-9 combined： in esophageal cancer, sensitivity=42%, NPV=63.29%, SE=0.078 （95% CI： 0.0159-0.322）; gastric cancer, sensitivity=S8%, NPV=70.42%, SE=0.072 （9$% CI： -0.0866-0.198）; and colon cancer, sensitivity=72%, NPV=78.12%, SE=0.070 （9S% CI： 0.137-0.415）. Conclusion： CEA exhibited the highest sensitivity for colon cancer, and CA19-9 exhibited the highest sensitivity for gastric cancer. Combined analysis indicated an increase in diagnostic sensitivity in esophageal and gastric cancer compared with that in colon cancer.

Receptor-binding cancer antigen expressed on SiSo cells can be detected in metastatic lymph nodes from gastrointestinal cancers

AIM： To investigate the expression of receptor-binding cancer antigen expressed on SiSo cells （RCAS1） in metastatic lymph nodes from gastrointestinal cancer. METHODS： Metastatic lymph nodes from gastrointestina cancer were detected for RCAS1 by immunohistochemica staining and mRNA in situ hybridization.RESULTS： A total of 102 metastatic lymph nodes from bile duct, gastric, colon, and pancreatic cancer were investigated for RCAS1 expression. The immunoreactivity of RCAS1 was identified in 100% of metastatic lymph nodes. Both local and distant metastatic lymph nodes showed RCAS1 expression. On the contrary, specimens of non-cancerous lymph nodes were negative for RCAS1. The result of mRNA in situ hybridization was also confirmed by the finding of immunohistochemical staining. RCAS1 mRNA was detected in all tumor cells that metastasized to lymph nodes. CONCLUSION： All metastatic lymph nodes express RCAS1 in tumor cells at both protein and mRNA levels, and RCAS1 should be used as a complementary factor for identification of metastatic lymph nodes from gastrointestinal cancers.

Role of computed tomographic colonoscopy of postoperative surveillance in patient with gastric cancer

AIM： TO examine the diagnostic yield of colorectal neoplasia at computed tomographic colonoscopy （CTC） as well as the feasibility of contrast enhanced CTC in patients with gastric cancer. METHODS： To examine the incidence of colon polyp we selected postoperative 188 gastric cancer patients, which we refer to as the ‘colon polyp survey group’. To examine the feasibility of CTC for early detection of colon cancer or advanced colon adenoma, we selected 47 gastric cancer patients （M：F 29：18, mean age 53.8 years）, which we call the ‘CT colonoscopy group’. All the 47 patients underwent successive CTC and colonoscopy on the same day. RESULTS： Totally 109 colon polyps were observed from 59 out of 188 gastric cancer patients, the inddence rate of colon polyps in gastric cancer patients being 31.4%. The sensitivity of CTC in detecting individuals with at least 1 lesion of any size was 57.1%, the specificity was 72.7%, the positive predictive value was 47.1%, and the negative predictive value was 71.9%. When the cutoff size was decreased to 6 mm, the sensitivity and specificity were 80.0% and 92.9%, respectively, with positive and negative predictive values of 57.1% and 97.5%, respectively. Only one patient was classified as false negative by virtual colonoscopy. CONCLUSION： The diagnostic yield of colorectal polyp was 31.4% in patients with gastric cancer, and contrast enhanced CTC is an acceptable tool for the detection of synchronous colorectal advanced adenoma and postoperative surveillance of gastric cancer patients.

Clinical analysis of 13 cases of synchronous gastric and colorectal cancer

Objective:To investigate the clinical characteristics and prognosis of patients with synchronous gastric and colorectal cancer.Methods:Clinical and pathological data of 3416 cases with gastric cancer and 3109 with colorectal cancer, from March 1985 to May 2005,were analyzed retrospectively.Results:Thirteen cases were confirmed as synchronous gastric and colorectal cancer and the incidences of the disease were 0.38%in gastric cancer cases and 0.42%in colorectal cancer.Of patients suffering from synchronous gastric and colorectal cancer,15.4%were diagnosed before the first operation and 33.3%were not diagnosed with the second cancer until it was radically dissected.The 3-year survival rate of the patients was 30.8%.Conclusion:The preoperative diagnosis rate of the synchronous gastric and colorectal cancer,the radical dis- section rate of the second cancer and the 3-year survival rate after surgical removal of the second cancer were rather low.The key for enhancing the radical dissection rate of the second cancer and the survival rate after surgery for the second cancer lies in the improvement of diagnosis rate before the first operation.