Convergence of Genetic, Nutritional and Inflammatory Factors in Gastrointestinal Cancers

Gastrointestinal cancers account for 20% of all cancer incidences worldwide. Colorectal cancer is the second most common cause of all cancer-related mortality and is increasing in Western societies. Infection and inflammation contribute to 15–20% of all malignancies, and are predisposing risk factors for gastrointestinal cancers. Helicobacter pylori infection is commonly associated with gastric cancers, and chronic inflammation increases the risk of colorectal cancer by 1% per year. Micronutrient status and common genetic variations in human populations modify risk for gastrointestinal cancer. Chronic inflammation promotes carcinogenesis by inducing gene mutations, inhibiting apoptosis, and stimulating an-giogenesis and cell proliferation. Inflammation also induces epigenetic alterations that are associated with cancer development. Two key genes in the inflammatory process, cyclooxygenase-2 (COX-2) and nuclear factor-kappa B (NF-kB), provide a mechanistic link between inflammation and cancer and are targets for chemoprevention. Dietary components, and human genetic variation that affects nutrient utilization, can directly modify inflammatory processes and/or suppress genomic alterations that are the molecular antecedents of cancers. The present report focuses on the convergence of genetic, nutritional, and inflammatory factors in the initiation and progression of gastrointestinal cancers, and the emerging dietary strategies for cancer prevention.     

Central tumour necrosis factor-α mediates the early gastrointestinal motor disturbances induced by lipopolysaccharide in sheep

Cytokines are involved in fever and other symptoms of the acute phase response induced by endotoxins. The aim of this work was to study the involvement of central tumour necrosis factor-alpha (TNF-alpha) in the changes induced by lipopolysaccharide (LPS) on gastrointestinal (GI) motility in sheep. Body temperature and myoelectric activity of the antrum, duodenum and jejunum was recorded continuously. Intravenous (i.v.) administration of LPS (0.1 micro g kg-1)-induced hyperthermia, decreased gastrointestinal myoelectric activity and increased the frequency of the migrating motor complex (MMC). These effects started 40-50 min after LPS and lasted for 6-7 h. TNF-alpha (50 and 100 ng kg-1) mimicked these effects when injected intracerebroventricularly (i.c.v.) but not i.v. Pretreatment with soluble recombinant TNF receptor (TNFR:Fc, 10 micro g kg-1, i.c.v.) abolished the TNF-induced actions and reduced those evoked by LPS. Furthermore, the effects induced by either LPS or TNF were suppressed by prior i.c.v. injection of indomethacin (100 micro g kg-1). In contrast, the i.v. injections of TNFR:Fc or indomethacin were ineffective. Our data suggest that LPS disturbs GI motility in sheep through a central pathway that involves TNF-alpha and prostaglandins sequentially.     

Tumour cell u-PA as a cause of fibrinolytic bleeding in metastatic disease

Tumour cells may express urokinase type plasminogen activator (u-PA). This may influence the invasive properties of the cells but has seldom been implicated in production of a systemic bleeding state. Two patients are described in whom severe bleeding occurred in association with disseminated malignancies. Thrombin generation was little disturbed and platelet numbers were insufficient to account for the bleeding. Florid plasmin generation was evident in the circulation and the fibrinolytic inhibitor tranexamic acid controlled the bleeding well. Free active u-PA was demonstrated in the circulation and u-PA antigen on the malignant cells which invaded the marrow of one of the patients. Tumour cell u-PA may occasionally be responsible for a bleeding state.     

Splanchnic ischaemia and its role in multiple organ failure

Multiple organ failure remains the leading cause of death in the intensive care unit. Increasing numbers of investigators have focused their attention on the role of gastrointestinal tract in the pathogenesis of this syndrome. Their data indicate that inadequate gut perfusion leads to a measurable imbalance between oxygen delivery and the needs of the tissues, i.e., ischaemia. Gut ischaemia of sufficient duration impairs gastrointestinal tract barrier function, facilitating the passage of enteric bacterial endotoxin into the circulation. It has been hypothesized that production of tumor necrosis factor α, and other biologic mediators by endotoxin–stimulated macrophages, triggers a generalized and uncontrolled inflammatory response that ultimately leads to multiple organ failure.
Preliminary evidence suggests that survival can be improved significantly if gut ischaemia is promptly identifed and aggressively treated by administration of fluids and inotropic drugs, using gastric intramucosal pH as the therapeutic endpoint. Future studies are needed to determine whether additional treatment modalities can improve outcome once the inflammatory response has fully developed.     

API2对黏膜相关淋巴瘤凋亡及凋亡相关蛋白的影响

目的：了解黏膜相关淋巴瘤的凋亡水平及其所涉及到的信号传导通路。方法：收集33例胃肠黏膜相关淋巴样组织(MALT)淋巴瘤病例，通过TUNEL技术原位检测MALT淋巴瘤肿瘤细胞的凋亡水平，通过逆转录聚合酶链反应(RT-PCR)和免疫组织化学染色检测肿瘤的凋亡抑制蛋白2编码基因(API2)和Caspase3 mRNA及蛋白，对API2和Caspase3水平作半定量和定量分析。根据凋亡检测结果将全部病例分为两组，即凋亡细胞数每50个高倍视野小于或等于2的病例组和大于2的病例组，比较2组的API2和Caspase3 mRNA及蛋白。结果：半数以上的MALT淋巴瘤中存在凋亡抑制；凋亡抑制的MALT淋巴瘤病例中API2 mRNA及蛋白水平明显高于没有明显凋亡抑制的病例，但Caspase3 mRNA及蛋白水平在两组病例中表达没有明显的差异。结论：MALT淋巴瘤中存在明显的凋亡抑制，其发生与凋亡抑制因子API2的表达上调有关，但API2对凋亡的调节与Caspase3有关的信号传导通路无明显相关。     

膀胱冲洗液适宜温度的临床探讨

目的 :确定最适温度的膀胱冲洗液 ,最大限度的减少膀胱痉挛的次数和强度 ,减少出血 ,提高病人生活质量。方法 :采用六组不同温度冲洗液对术后病人行持续膀胱冲洗 ,记录膀胱痉挛次数 ,膀胱出血程度及体温变化的情况。结果 :随着冲洗液温度升高 ,膀胱痉挛平均次数减少 ,冲洗前后患者体温差逐渐变小 ,2 0℃～ 3 0℃温度组术后冲洗液红细胞计数平均数明显低于其它温度组。结论 :2 0℃～ 3 0℃是持续膀胱冲洗的最适温度     

下肢深静脉血栓形成83例的病因分析

目的：探索下肢深静脉血栓形成的发病原因。方法：回顾1994年1月至2003年1月10年来所收集病人资料83例。结果：48例(占58％)病人病因明确，35例(占42％)病因不明。结论：血液高凝状态、下肢静脉血流缓慢、静脉内膜损伤三个因素综合作用造成了下肢深静脉血栓形成的发生。术后早期下床活动、抗血小板聚集可预防下肢深静脉血栓形成的发生。     

高危出血患者应用吉派林抗凝血液透析疗效观察

目的：观察危重型肾功能衰竭合并高危出血患者选择抗凝药物进行血液透析治疗的效果。方法：应用吉派林(低分子肝素钠)作为抗凝剂进行血液透析。结果：129例病人进行血液透析386次，均没有出血发生。结论：吉派林在高危出血患者血液透析中使用方便，安全，效果良好。     

人工全髋置换术中拉钩对下肢深静脉血栓影响的研究

目的：通过对髂外动静脉及股动静脉与髋臼解剖学与临床的研究，探讨在全髋臼置换术中拉钩在髋放置位置对下肢深静脉血栓的影响。方法：通过解剖学研究56具成年骨盆标本中髂外动静脉及股动静脉来源及走行、与髋臼的关系进行测量分析；并通过临床观察22例（股骨颈骨折12例、股骨头缺血性坏死6例、类风湿性关节炎4例）在人工全髋置换术（THR）中拉钩放置安全区，经下肢静脉超声多普勒检查观察下肢深静脉血栓发病率。结果：在左侧3-5点间、右侧7-9点、左侧9点、右侧3点使用拉钩用力要适度，牵拉时间过长，会造成臀下血管、股动脉的牵拉过度或时间过长，易引起下肢深静脉血栓；通过临床22例THR拉钩放置安全区的观察，无一例下肢深静脉血栓，仅有2例轻度深静脉血流缓慢、但无明显的症状体征，经过口服活血通络中药后消失。结论：通过解剖学与临床观察研究，确定在THR中拉钩放置位置、深度是避免下肢深静脉血栓的重要因素。     

生长抑素治疗食管胃底静脉曲张破裂出血的临床研究

目的 探讨生长抑素治疗食管胃底静脉曲张破裂出血的临床效果。方法 应用奥曲肽治疗食管胃底静脉曲张破裂出血患者41例,并与垂体后叶素治疗的32例及三腔管治疗的25例进行对照。观察3组平均止血时间、24h止血率以及治疗前后门静脉主干直径、血流速度、血流量的变化。结果 奥曲肽治疗组、垂体后叶素治疗组、三腔管治疗组平均止血时间分别为194.27±28.88min、358.11±151.43min、134.71±32.12min,24h止血率分别为63.41％、37.50％、72％。奥曲肽治疗组止血率显著高于垂体后叶素治疗组(P<0.01)。奥曲肽治疗前后门静脉内径分别为10.86±0.41mm、13.84±0.35mm,二者有显著差异。奥曲肽治疗后其门静脉血流速度,血流量与治疗前相比较也有显著差异(P<0.01,P<0.05)。结论 奥曲肽能使门脉内径相对缩小、血流量减少和血流速度加快,从而使门脉压力降低达到止血的目的。