腹腔镜切除与内镜联合治疗胃肠道肿瘤的效果观察

目的：分析腹腔镜联合内镜治疗胃肠道肿瘤的可行性和临床效果。方法：对我院收治的行腹腔镜切除与内镜联合治疗的75例胃肠道肿瘤患者的临床资料进行回顾性分析,其中腹腔镜与胃镜联合治疗34例,腹腔镜与肠镜联合治疗41例。总结分析治疗效果。结果：75例患者中有72例手术成功,3例患者因肿瘤位置不佳中转开腹,腹腔镜与胃镜联合平均手术时间（72.8±12.7）min,出血量5~30mL,术后无吻合口瘘、吻合口出血、腹腔感染等并发症,住院时间（7.5±0.5）d。结论：腹腔镜联合内镜治疗胃肠道肿瘤具有创伤小、手术安全的特点,是一种有效、安全的治疗手段,值得临床推广应用。     

50例胃肠道间质瘤的临床病理分析

目的：探讨胃肠道间质瘤（GIST）的组织形态学特征及对该类肿瘤的诊断及预后问题。方法：对发生于2001年4月至2010年4月间的50例GIST进行临床病理及免疫组化分析。结果：50例GIST免疫组化检查结果,肿瘤均不表达CK而表达为Vimentin;CD117阳性表达43例,CD34阳性表达38例;S100均有不同程度表达,SMA阳性表达22例,Desmin阳性表达15例;Ki-67均有表达,其阳性度从＋．＋＋不等。结论：本组肿瘤中所有病例均不同程度表达Ki-67和PCNA,高危险性的阳性表达强、低危险性的阳性表达弱。这说明GIST的预后除与肿瘤的大小、组织形态学的改变及肿瘤的发生部位有关外,还与Ki-67和PCNA在肿瘤中的表达程度有关。     

胃肠道间质瘤临床诊治-附46例临床分析

目的:探讨胃肠间质瘤(Gastrointestinal Stromal Tumor,GIST)的临床特点及诊断及治疗方法。方法:回顾性分析我院1997-2009年收治的46例有完整病历资料的GIST病例,以探讨GIST的主要发生部位、临床表现、诊断和治疗方法。结果:GIST主要发生在胃(60.87%)和小肠(26.09%);主要表现为消化道出血(71.74%),腹痛不适(19.57%),腹部包块(15.22%)等;诊断首选B超(阳性率45.65%)、CT(阳性率100%)和内窥镜检查(阳性率81.09%)。本组手术45例,根治性切除40例,姑息性切除3例,术中活检1例,局部切除1例,1例放弃治疗。所有病例均经病理证实。随访42例,复发死亡11例,带瘤生存8例,无瘤生存21例,3例术后口服格列卫(甲磺伊马替尼,ST1571)的病人已生存8月、14月、18月。结论:目前GIST的治疗仍以手术治疗为主,分子靶向制剂的应用显示了一定的治疗效果。     

Selecting Tyrosine Kinase Inhibitors for Gastrointestinal Stromal Tumor with Secondary KIT Activation-Loop Domain Mutations

Advanced gastrointestinal stromal tumors (GIST), a KIT oncogene-driven tumor, on imatinib mesylate (IM) treatment may develop secondary KIT mutations to confer IM-resistant phenotype. Second-line sunitinib malate (SU) therapy is largely ineffective for IM-resistant GISTs with secondary exon 17 (activation-loop domain) mutations. We established an in vitro cell-based platform consisting of a series of COS-1 cells expressing KIT cDNA constructs encoding common primary±secondary mutations observed in GISTs, to compare the activity of several commercially available tyrosine kinase inhibitors on inhibiting the phosphorylation of mutant KIT proteins at their clinically achievable plasma steady-state concentration (Css). The inhibitory efficacies on KIT exon 11/17 mutants were further validated by growth inhibition assay on GIST48 cells, and underlying molecular-structure mechanisms were investigated by molecular modeling. Our results showed that SU more effectively inhibited mutant KIT with secondary exon 13 or 14 mutations than those with secondary exon 17 mutations, as clinically indicated. On contrary, at individual Css, nilotinib and sorafenib more profoundly inhibited the phosphorylation of KIT with secondary exon 17 mutations and the growth of GIST48 cells than IM, SU, and dasatinib. Molecular modeling analysis showed fragment deletion of exon 11 and point mutation on exon 17 would lead to a shift of KIT conformational equilibrium toward active form, for which nilotinib and sorafenib bound more stably than IM and SU. In current preclinical study, nilotinib and sorafenib are more active in IM-resistant GISTs with secondary exon 17 mutation than SU that deserve further clinical investigation.     

Helicobacter pylori Eradication Prevents Metachronous Gastric Neoplasms after Endoscopic Resection of Gastric Dysplasia

Purpose

There is insufficient data about the role of eradication of H. pylori after endoscopic resection (ER) for gastric dysplasia. The aim was to investigate the benefit of H. pylori eradication after ER in patients with gastric dysplasia to prevent metachronous gastric neoplasms.

Materials and Methods

We retrospectively reviewed 1872 patients who underwent ER of gastric dysplasia. We excluded patients with a follow-up period of <2 years or who had not undergone tests for active H. pylori infection. A total of 282 patients were enrolled. The patients were categorized into those without active H. pylori infection (H. pylori-negative group, n = 124), those who successfully underwent H. pylori eradication (eradicated group, n = 122), and those who failed or did not undergo H. pylori eradication (persistent group, n = 36).

Results

Metachronous recurrence was diagnosed in 36 patients, including 19 in the H. pylori-negative group, 10 in the eradicated group, and 7 in the persistent group. The cumulative incidence of metachronous recurrence was significantly lower in the H. pylori-eradicated group in comparison with either of the H. pylori-persistent (non-eradicated or failed) groups (p = 0.039). Similarly, the incidence of metachronous recurrence was significantly lower in the H. pylori-eradicated group compared with the H. pylori-negative group (p = 0.041).

Conclusion

Successful H. pylori eradication may reduce the development of metachronous gastric neoplasms after ER in patients with gastric dysplasia.     

内镜黏膜下剥离术和挖除术治疗上消化道肿瘤的疗效及安全性分析

目的:分析内镜黏膜下剥离术(ESD)和黏膜下挖除术(ESE)治疗上消化道肿瘤的疗效及安全性。方法:回顾性分析2017年1月至2019年4月我院消化内科接受ESD或ESE治疗的68例上消化道肿瘤住院患者的临床资料,收集患者基础疾病、手术时间、病变部位大小、整块切除率、并发症等资料,同时采用Logistic回归分析对术中穿孔进行危险因素分析。结果:64例患者完整切除瘤体(94.12%),肿瘤平均直径(16.98±8.29)mm。食管病灶病理类型以高级别上皮内瘤变为主,有15例(22.06%);胃部病灶分布以胃体、胃底和胃窦居多,分别有18例(26.47%)、16例(23.53%)和12例(17.65%),病理类型以间质瘤最多,占36.76%;11例患者发生并发症(16.18%),4例患者出现术后出血(5.88%),经过内镜下止血后好转,8例患术中穿孔(11.76%),均行内镜下尼龙绳联合钛夹行荷包缝合,其中1例患者术中穿孔合并术后迟发性出血;病灶最大直径(≥25 mm,P=0.036)和病灶部位(胃底,P=0.015)是导致ESD或ESE术中穿孔的独立危险因素。结论:ESD和ESE治疗上消化道肿瘤安全有效,但需注意病灶大小和胃底病变,因其是导致术中穿孔的独立危险因素。     

Cost-Effectiveness of Eradication of Helicobacter pylori in Gastric Cancer Survivors After Endoscopic Resection of Early Gastric Cancer

Background:  Clinical effectiveness of Helicobacter pylori eradication in gastric cancer survivors after endoscopic resection of early gastric cancer (EGC) was recently established in a randomized controlled trial. We aimed to establish long-term cost-effectiveness in gastric cancer survivors after endoscopic resection of EGC.
Materials and Methods:  A Markov model was constructed to compare the costs and outcomes of the two intervention strategies: (1) eradicate H. pylori after complete resection of EGC by endoscopy (2) do not eradicate. Estimates for variables in the model were obtained by extensive review of published reports. Analyses were made from the Korean public healthcare provider's perspective.
Results:  Base-case analysis indicated H. pylori eradication costs less (US$ 29,780 vs. US$ 30,594) than no eradication, and save more lives (mean life expectancy from eradication: 13.60 years vs. 13.55 years). One-way and three-way sensitivity analyses showed the robustness of the cost-effectiveness results.
Conclusion:  In this selective population with very high risk of developing gastric cancer, H. pylori eradication should be considered for reimbursement with priority to prevent subsequent cancer and also reduce health care cost.     

Fractioned Dose Regimen of Sunitinib for Patients with Gastrointestinal Stromal Tumor: A Pharmacokinetic and Treatment Efficacy Study

AIM: Sunitinib has shown benefit in patients with imatinib (IM)–resistant gastrointestinal stromal tumor (GIST). However, its advantages are somewhat diminished because of associated toxicities. Herein, we clarify the efficacy and safety of fractioned dose regimen of sunitinib by a pharmacokinetic and efficacy study. MATERIALS AND METHODS: Between 2001 and March 2013, a total of 214 patients with metastatic GIST was treated at Chang Gung Memorial Hospital. Among them, 55 (11.6%) patients who received sunitinib were investigated. One group of patients was administered with standard dose of once-daily sunitinib (standard dose group) and the other group was administered with standard total daily dose of sunitinib in fractioned doses (fractioned dose group). RESULTS: Thirty-two male and 23 female patients with a median age of 55 years received sunitinib. The median duration of sunitinib administration was 9.2 months. The clinical benefit was 65.2%. The mean peak blood level of sunitinib in patients with fractioned doses was significantly lower than that in those with once-daily dose (83.4 vs 50.1 ng/ml, P = .01). The rates of adverse effects of hand-foot syndrome, mucositis, and yellow skin were significantly decreased by fractioned doses of sunitinib. However, the progression-free and overall survival did not differ between patients with different treatment regimens. CONCLUSION: The fractioned dose regimen of sunitinib appears to be a safe and effective treatment for patients with IM-resistant/intolerant GISTs. Significantly decreased toxicity of this regimen could be explained by significantly lower peak sunitinib blood level. However, the treatment efficacy is not reduced by this regimen.     

腔镜下甲状腺手术与传统开放性手术临床疗效对比

目的:比较腔镜下甲状腺手术与传统开放性甲状腺手术的临床治疗效果。方法:对2009年1月至2013年3月在我院行腔镜下甲状腺手术与传统开放手术治疗的200例患者进行分析比较,其中腔镜甲状腺手术组102例(腔镜组),传统开放手术组98例(传统组),比较两组的手术时间、术中出血量、术后引流量、拔管时间、住院时间、术后3及6个月美容效果评分(numerical score system,NSS)及并发症情况。结果:200例腔镜甲状腺手术成功完成,无中转开放手术;腔镜组平均手术时间、引流总量,拔管时间以及住院时间均明显高于传统组,差异具有统计学意义(P0.05);术中出血量则明显低于传统组(P0.05);术后腔镜组声音嘶哑、饮水呛咳及颈部感觉异常等并发症明显低于传统组(P0.05),而皮下积液和皮下气肿明显高于传统组(P0.05);腔镜组术后3个月及术后6个月NSS评分均明显高于传统组,差异有统计学意义(P0.05)。结论:腔镜下甲状腺手术临床疗效较传统开放性手术相比,具有手术出血较少,神经损伤率低以及美容效果优异等优势,但也存在一些并发症,需严格按照其适应证对患者进行选择,尊重患者自主选择权,增进医患和谐。     

Stromal Cells Induce Th17 during Helicobacter pylori Infection and in the Gastric Tumor Microenvironment

Gastric cancer is associated with chronic inflammation and Helicobacter pylori infection. Th17 cells are CD4⁺ T cells associated with infections and inflammation; but their role and mechanism of induction during carcinogenesis is not understood. Gastric myofibroblasts/fibroblasts (GMF) are abundant class II MHC expressing cells that act as novel antigen presenting cells. Here we have demonstrated the accumulation of Th17 in H. pylori-infected human tissues and in the gastric tumor microenvironment. GMF isolated from human gastric cancer and H. pylori infected tissues co-cultured with CD4⁺ T cells induced substantially higher levels of Th17 than GMF from normal tissues in an IL-6, TGF-β, and IL-21 dependent manner. Th17 required interaction with class II MHC on GMF for activation and proliferation. These studies suggest that Th17 are induced during both H. pylori infection and gastric cancer in the inflammatory milieu of gastric stroma and may be an important link between inflammation and carcinogenesis.     

内镜下黏膜切除术治疗胃息肉的疗效及对血清ProGRP、PGI水平的影响

摘要 目的：探讨内镜下黏膜切除术治疗胃息肉的疗效及对血清胃泌素释放肽前体（ProGRP）、胃蛋白酶原I（PGI）水平的影响。方法：选取我院2019年8月到2022年8月收治的120例胃息肉患者作为研究对象，依照手术方式的不同进行分组，其中将选择常规内镜下电凝切除术治疗的60例患者分为对照组，选择内镜下黏膜切除术治疗的60例患者分为观察组。对比两组患者不良反应发生情况与治疗费用，手术前与手术后血清ProGRP、PGI表达水平以及炎症因子表达水平，对比两组患者整体切除率和并发症发生情况。结果：两组患者总治疗费用对比无差异（P＞0.05），观察组患者术后不良反应发生率较对照组低（P＜0.05）；两组患者手术前血清ProGRP、PGI水平对比无差异（P＞0.05），治疗后两组患者均降低，且观察组较对照组低（P＜0.05）；两组患者手术前PCT、CRP、IL-6、IL-2对比无明显差异（P＞0.05），手术后两组患者PCT、CRP、IL-6、IL-2均升高，且观察组低于对照组（P＜0.05）；两组患者胃息肉均被完整切除，整体切除率对比无差异；且观察组穿孔、迟发性出血以及感染等并发症发生率虽低于对照组，但比较无差异（P＞0.05）。结论：对胃息肉患者采取内镜下黏膜切除术与常规内镜下电凝切除术均能够完整的切除胃息肉，且治疗费用相当。而应用内镜下黏膜切除术能够降低患者ProGRP、PGI水平，降低机体炎症因子反应，且并发症发生率较低，值得临床应用推广。     

Small bowel Gastrointestinal Stromal Tumors can physiologically alter gut motility before causing mechanical obstruction

Background

Gastro Intestinal Stromal Tumors (GISTs) are rare stromal neoplasms that represent the most common mesenchymal tumor of the G.I. tract, accounting for 5% of all sarcomas [1, 2]. Originating from interstitial cells of Cajal, which are regulators of gut peristalsis, they are preferentially located in the stomach and the small intestine [3] and clinical presentation is variable, ranging from vague complaints to major G.I. bleeding. Surgical resection is the mainstay of treatment for patients with resectable GIST and 5-year survival ranges from 21% to 88% in different series depending on risk grading and completeness of surgical resection [4, 5]. Imatinib mesylate, a tyrosine kinase inhibitor, provides an encouraging option for treating high risk GISTs.

Case presentation

We report the case of a 62-year-old lady who had been diagnosed and being treated unsuccessfully for Irritable bowel syndrome for 11 years and eventually found to have an obstructing small bowel GIST.

Conclusion

The symptoms from GIST may mimic those of irritable bowel syndrome. A physiological alteration in gut peristalsis resulting from neoplastic transformation of the interstitial cells of Cajal, is a hypothesis that could explain this presentation. An alternative diagnosis should be considered when treating patients with irritable bowel syndrome who fail to respond for a prolonged period.