临床研究的体会

黎介寿院士从医数十年,见证了中国外科的成长,并在临床工作和研究中为医疗事业进步作出了众多重要的贡献。本文中,笔者结合自己的从医以来在"肠功能障碍"、"快速康复外科"、"小肠移植"等诸多方向上令人瞩目的研究经历,深刻的探讨了医疗研究中发现和解决问题的态度和方法,对广大医生的临床实践有着重要的指导意义。     

Combination of Adult Intussusception and Intestinal Malrotation: An Unusual Presentation

Intussusception is familiar to pediatric surgeons but is rarely encountered by general surgeons. Adult intussusception is uncommon, accounting for less than 5% of intestinal obstructions, half of which are associated neoplasms. Intestinal malrotation is usually an incidental finding with unrelated disease on image studies, laparotomy or even autopsy. The major complications of intestinal malrotation are intestinal obstruction secondary to midgut volvulus, internal hernia, or adhesion band. The association of the two entities, which is named Waugh’s syndrome in infants, has rarely been reported in the literature. The association in adults is even rarer. We report an adult case with an unusual combination of malrotation and intussusception at exploration.     

Phasic study of intestinal homeostasis disruption in experimental intestinal obstruction

AIM: To investigate the phasic alteration of intestinal homeostasis in an experimental model of intestinal obstruction.METHODS: A rabbit model of intestinal obstruction was established by transforming parts of an infusion set into an in vivo pulled-type locking clamp and creating a uniform controllable loop obstruction in the mesenteric non-avascular zone 8 cm from the distal end of the ileum. The phasic alteration of intestinal homeostasis was studied after intestinal obstruction. The changes in goblet cells, intraepithelial lymphocytes, lamina propria lymphocytes, and intestinal epithelium were quantified from periodic acid-Schiff-stained sections. Ornithine decarboxylase (ODC) activity and serum citrulline levels were measured by high-performance liquid chromatography. Claudin 1 mRNA expression was examined by real-time polymerase chain reaction analysis. Intestinal microorganisms, wet/dry weight ratios, pH values, and endotoxin levels were determined at multiple points after intestinal obstruction. Furthermore, the number and ratio of CD3⁺, CD4⁺ and CD8⁺ T cells were determined by flow cytometry, and secretory IgA levels were measured with an enzyme-linked immunosorbent assay.RESULTS: A suitable controllable rabbit model of intestinal obstruction was established. Intestinal obstruction induced goblet cell damage and reduced cell number. Further indicators of epithelial cell damage were observed as reduced serum citrulline levels and claudin 1 gene expression, and a transient increase in ODC activity. In addition, the wet/dry weight ratio and pH of the intestinal lumen were also dramatically altered. The ratio of Bacillus bifidus and enterobacteria was reversed following intestinal obstruction. The number and area of Peyer’s patches first increased then sharply decreased after the intestinal obstruction, along with an alteration in the ratio of CD4/CD8⁺ T cells, driven by an increase in CD3⁺ and CD8⁺ T cells and a decrease in CD4⁺ T cells. The number of lamina propria lymphocytes also gradually decreased with prolonged obstruction.CONCLUSION: Intestinal obstruction can induce disruption of intestinal homeostasis.     

Distribution of bleeding gastrointestinal angioectasias in a Western population

AIM: To define which segments of the gastrointestinal tract are most likely to yield angioectasias for ablative therapy.METHODS: A retrospective chart review was performed for patients treated in the Louisiana State University Health Sciences Center Gastroenterology clinics between the dates of July 1, 2007 and October 1, 2010. The selection of cases for review was initiated by use of our electronic medical record to identify all patients with a diagnosis of angioectasia, angiodysplasia, or arteriovenous malformation. Of these cases, chart reviews identified patients who had a complete evaluation of their gastrointestinal tract as defined by at least one upper endoscopy, colonoscopy and small bowel capsule endoscopy within the past three years. Patients without evidence of overt gastrointestinal bleeding or iron deficiency anemia associated with intestinal angioectasias were classified as asymptomatic and excluded from this analysis. Thirty-five patients with confirmed, bleeding intestinal angioectasias who had undergone complete endoscopic evaluation of the gastrointestinal tract were included in the final analysis.RESULTS: A total of 127 cases were reviewed. Sixty-six were excluded during subsequent screening due to lack of complete small bowel evaluation and/or lack of documentation of overt bleeding or iron deficiency anemia. The 61 remaining cases were carefully examined with independent review of endoscopic images as well as complete capsule endoscopy videos. This analysis excluded 26 additional cases due to insufficient records/images for review, incomplete capsule examination, poor capsule visualization or lack of confirmation of typical angioectasias by the principal investigator on independent review. Thirty-five cases met criteria for final analysis. All study patients were age 50 years or older and 13 patients (37.1%) had chronic kidney disease stage 3 or higher. Twenty of 35 patients were taking aspirin (81 mg or 325 mg), clopidogrel, and/or warfarin, with 8/20 on combination therapy. The number and location of angioectasis was documented for each case. Lesions were then classified into the following segments of the gastrointestinal tract: esophagus, stomach, duodenum, jejunum, ileum, right colon and left colon. The location of lesions within the small bowel observed by capsule endoscopy was generally defined by percentage of total small bowel transit time with times of 0%-9%, 10%-39%, and 40%-100% corresponding to the duodenum, jejunum and ileum, respectively. Independent review of complete capsule studies allowed for deviation from this guideline if capsule passage was delayed in one or more segments. In addition, the location and number of angioectasias observed in the small bowel was further modified or confirmed by subsequent device-assisted enteroscopy (DAE) performed in the 83% of cases. In our study population, angioectasias were most commonly found in the jejunum (80%) followed by the duodenum (51%), stomach (22.8%), and right colon (11.4%). Only two patients were found to have angioectasias in the ileum (5.7%). Twenty-one patients (60%) had angioectasias in more than one location.CONCLUSION: Patients being considered for endoscopic ablation of symptomatic angioectasias should undergo push enteroscopy or anterograde DAE and re-inspection of the right colon.     

肠道菌群与1型糖尿病的关系

1型糖尿病发病机制与遗传因素、环境因素及自身免疫因素均有关,是在遗传因素基础上,由环境因素启动,以T淋巴细胞介导的胰岛β细胞进行性损伤为主要特征的自身免疫性疾病.肠道菌群作为环境因素与1型糖尿病发生有直接关系,可通过改变肠壁通透性和宿主免疫系统影响发病.肠道菌群、宿主免疫及1型糖尿病三者之间存在相互联系,研究肠道菌群可为1型糖尿病的预防和治疗提供线索.     

隐源性多灶性溃疡性狭窄性小肠炎

隐源性多灶性溃疡性狭窄性小肠炎(CMUSE)是一种以小肠多部位狭窄和多灶性浅溃疡为特点的小肠疾病,主要的临床表现为慢性或复发性肠梗阻。溃疡一般较浅,位于黏膜层和黏膜下层。纤维性狭窄部位较短(一般1~2 cm),相互间隔较紧凑(多为2~10 cm),无瘘管形成。外科手术治疗后复发率高,糖皮质激素可有效防止再次手术,多数患者成为激素依赖状态。     

Safety and efficacy of home parenteral nutrition for chronic intestinal failure: a 16-year experience at a single centre

BACKGROUND: Comparisons between safety and efficacy of home parenteral nutrition and of intestinal transplantation for treatment of chronic intestinal failure derived from observational studies. AIMS: To present the 16-year experience of home parenteral nutrition by the Chronic Intestinal Failure Centre of Bologna University. PATIENTS: A total of 40 adult patients were enrolled between 1986 and 2001. METHODS: Safety indices: survival and cause of death, catheter-related bloodstream infection, deep vein thrombosis, liver disease. Efficacy indices: nutritional and rehabilitation status, quality of life (SF36 instrument), re-hospitalisation rate. Statistics: Kaplan-Maier analysis and Cox model for survival probability and risk factors; logistic regression for catheter-related bloodstream infection risk factors. RESULTS: Survival rates at 1, 3 and 5 years were 97, 82 and 67% respectively. Survival was higher in patients < or = 40 years. One death was home parenteral nutrition-related. Incidence of catheter-related bloodstream infection: 0.30/year home parenteral nutrition, was lower in patients treated by a specialized nursing protocol. Incidence of deep vein thrombosis was 0.05/year home parenteral nutrition. Hepatosteatosis occurred in 55%. Body weight remained stable or increased in 80%. Rehabilitation was total or partial in 74%. Re-hospitalisation rate was 0.70/year home parenteral nutrition. Quality of life scored significantly lower than in healthy populations in six out of eight domains. CONCLUSIONS: Home parenteral nutrition is a safe and efficacious therapy for chronic intestinal failure. Survival compares favourably with survival after intestinal transplantation.     

老年人粪性结肠梗阻与穿孔诊治的体会

目的 分析老年人粪性结肠梗阻与穿孔的临床特征，以提高诊治水平。方法 对1994年1月至2003年12月收治的22例老年粪性结肠梗阻与6例粪性结肠穿孔患者资料进行回顾性分析。结果 粪性结肠梗阻22例，6例分别以肠梗阻、结肠占位病变行手术治疗，16例行保守治疗，均痊愈。粪性结肠穿孔6例，分别以结肠恶性肿瘤穿孔、肠绞窄行手术治疗，穿孔部位多见于直-乙状结肠交界处，2例因感染性休克、多器官功能衰竭死亡。结论 粪性结肠梗阻患者经保守治疗多能缓解症状。粪性结肠穿孔比较罕见，缺乏特异性临床表现，误诊率和病死率高，应积极行手术治疗，切除病变肠段、行Hartmann造瘘术为首选。     

肠道寄生虫感染与黏膜局部的抗感染免疫

肠道是许多病原体入侵的门户，宿主对入侵肠道的病原体可产生不同程度的抵抗力，表现为肠道黏膜的屏障作用和肠黏膜细胞、黏膜相关淋巴组织产生的一系列特异性和非特异性免疫反应等。寄生虫是单细胞或多细胞病原生物，其抗原成分相当复杂，因此，寄生虫抗原诱发的免疫应答大都是由多种免疫细胞和免疫因子参与的复杂过程。该文就肠道寄生虫与宿主肠黏膜细胞之间的相互作用和宿主肠道黏膜局部抗寄生虫感染的非特异性免疫和特异性免疫机制等进行综述。     

Jejuno-jejunal invagination due to intestinal melanoma

Cutaneous melanoma is one of the most studied neoplastic lesions in biology and clinical oncology. It has been well documented that this type of neoplasm presents a high metastatic rate, and is able to involve nearly every tissue. Non-cutaneous melanoma represents an unusual pattern of melanoma, and the small intestine is an uncommon anatomic localization. Herein we report an extremely rare clinical case of a young woman affected by a bleeding jejunal melanoma, whose early clinical presentation was an intestinal invagination.     

肠黏膜屏障损伤与保护分子机制研究进展

介绍肠黏膜屏障损伤因素的分子机制,如内毒素及氧自由基、炎症介质和细胞因子如白细胞介素（interleukin）、肿瘤坏死因子-α（TNF-α）、核转录因子kappa B、TOLL样受体（TLRs）和NOD受体通路、高迁移率族蛋白B1、烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶（NOX）等。对肠黏膜屏障的保护分子机制如肠上皮紧密连接蛋白、白介素家族、其它保护性调控因子等作出介绍。     

肠道平滑肌动力与炎症性肠病研究进展

肠道平滑肌动力改变与炎症性肠病(IBD)的发病关系得到医学界的重视,并逐渐成为IBD发病机制研究的热点.肠道运动的异常和神经递质的失衡在IBD的发生和进展过程中起了重要作用;白细胞介素能在一定程度上反映肠道运动功能变化.因此,恢复神经递质的失衡并重建肠道动力平衡的策略在IBD治疗过程中有良好的应用前景.     

Effects of intestinal mucosal blood flow and motility on intestinal mucosa

AIM:To investigate the role of intestinal mucosal blood flow(IMBF) and motility in the damage of intestinal mucosal barrier in rats with traumatic brain injury.METHODS:Sixty-four healthy male Wistar rats were divided randomly into two groups:traumatic brain injury(TBI) group(n = 32),rats with traumatic brain injury;and control group(n = 32),rats with sham-operation.Each group was divided into four subgroups(n = 8) as 6,12,24 and 48 h after operation.Intestinal motility was measured by the propulsion ratio o...     

食物过敏与肠道菌群的研究进展

食物过敏(food allergy,FA)是指机体针对摄入的食物蛋白产生的一种有害的免疫反应.2007年疾病预防与控制中心(CDC)数据显示,年龄在18岁以下儿童发生食物过敏者超过3百万(3.9%),5岁以下发病率更高.本文阐述了健康的肠道菌群对促使免疫系统成熟有非常重要的作用,食物过敏与非过敏婴儿间肠道菌群组成确实不同.儿童食物过敏与肠道黏膜屏障的破坏、黏膜屏障成分的发育不成熟、肠道菌群失调、肠道菌群紊乱密切相关.益生菌(probiotics)作为肠道微生态的平衡者和肠黏膜免疫系统调节者,对防治过敏性疾病的发生可能具有适度的作用,但需要更进一步的、更多的大样本随机对照临床研究.     

Intestinal glucose metabolism revisited

It is long known that the gut can contribute to the control of glucose homeostasis via its high glucose utilization capacity. Recently, a novel function in intestinal glucose metabolism (gluconeogenesis) was described. The intestine notably contributes to about 20–25% of total endogenous glucose production during fasting. More importantly, intestinal gluconeogenesis is capable of regulating energy homeostasis through a communication with the brain. The periportal neural system senses glucose (produced by intestinal gluconeogenesis) in the portal vein walls, which sends a signal to the brain to modulate hunger sensations and whole body glucose homeostasis. Relating to the mechanism of glucose sensing, the role of the glucose receptor SGLT3 has been strongly suggested. Moreover, dietary proteins mobilize intestinal gluconeogenesis as a mandatory link between their detection in the portal vein and their effect of satiety. In the same manner, dietary soluble fibers exert their anti-obesity and anti-diabetic effects via the induction of intestinal gluconeogenesis. FFAR3 is a key neural receptor involved in the specific sensing of propionate to activate a gut-brain reflex arc triggering the induction of the gut gluconeogenic function. Lastly, intestinal gluconeogenesis might also be involved in the rapid metabolic improvements induced by gastric bypass surgeries of obesity.