肠道菌群、癌症防治与益生菌(二)

(接上期P36)二益生菌及益生素益生菌指可以有效促进人类健康的特定细菌菌株,大多属天然肠道菌群,主要是乳杆菌属和双歧杆菌属。由于益生菌可缓解肠道炎症,降低腹泻发生率,具有降低罹患结肠癌风险、改善免疫系统的作用,因此食品级益生菌逐渐进入人们视野。     

单味龙血竭对急性放射性肠损伤的防护作用

目的:回顾性分析中药龙血竭预防急性放射性肠损伤的临床疗效。方法:2007年-2013年我院盆腔肿瘤术后放疗患者296例。预防组（157例）给予龙血竭胶囊口服（6～8粒/次,3次/d,与放疗同步）;对照组（139例）给予思密达口服（1包/次,3次/d,与放疗同步）。观察两组急性放射性肠损伤发生的时间、程度,并观察服用龙血竭后的不良反应发生情况。结果:预防组和对照组急性放射性肠损伤发生时间分别为放疗开始第12~30天（平均25天）和第2~35天（平均13天）,预防组发生时间明显晚于对照组。预防组和对照组急性放射性肠损伤总发生率、Ⅱ-Ⅳ级急性放射性肠损伤发生率分别为14.65%、32.37%和5.10%、15.83%,统计学分析均具有显著性差异（χ2=13.09,χ2=9.32,P＜0.01）。两组均未出现严重急性放射性肠损伤（Ⅳ级）。结论:龙血竭防治急性放射性肠损伤发生时间晚、发生率低、程度轻,临床预防效果满意。     

肠道菌群对放射性肠损伤防护作用的基础与临床研究进展

人类肠道中定殖着各种菌群,放射线作用下菌群分布会发生变化,同时菌群本身对肠道组织的放射敏感性也有一定调节作用,而人为对肠道菌群进行干预能有效改善放疗后的急性肠道损伤^[1-4]。笔者为探讨肠道菌群对放射性肠损伤的防护作用,用“radiation、enteritis、gut flora”为检索词检索了PubMed文库1990年以来文献,主要围绕肠道菌群在放射性肠损伤中的作用及分子机制进行选择,包含了临床试验和动物实验。现就肠道菌群与肠道放射性损伤及放射敏感性之间关系和相关机制进行总结。     

放射性肠炎

肠遭损伤常为腹部或盆腔的放射治疗结局之一而出现,而慢性放射性肠炎又是使发病率和死亡率增加的一个重要原因,本文重点就放射性肠炎治疗和预防的进展作一综述。症状及发病情况1.急性放射性肠炎在盆腔和/或腹部的放射治疗过程中,急性放射性肠炎在临床上常表现为伴有腹部痉挛(或无痉挛)的腹泻,它的发生几乎是无法避免的,这些症状常在盆腔常规放疗中的第3周出现。恶心和呕吐亦常发生,特别是在全腹部照射时。急性放射性肠炎一般在放疗后6周得到明显改善,但约20％的病人由于症状严重,     

125I组织间放疗与肠道组织损伤及防护

125I粒子组织问放疗易引起肠道组织损伤,其发生机制可能与肠道组织的更新速度快,处于M期、G2期及S后期的细胞多相关.肠道组织接受放疗的耐受剂量约为160 Gy,若吸收剂量大于其耐受剂量时即可发生肠道组织的放射性损伤.在125I组织间放疗的临床应用中,粒子植入前通过治疗计划系统制定科学、严密的计划,操作过程中应用超声、CT、MRI及其他影象学技术进行准确的定位,在粒源和肠道组织间设置适当的屏障保护,可以减少肠道组织的放射性损伤.     

急性放射性粘膜炎的发生机理及防治的研究进展

放疗是头颈部肿瘤尤其是鼻咽癌的重要治疗手段之一,根治性放疗往往会引起放射性损伤。急性放射性粘膜炎是放疗中常见的严重毒副反应,发生率高,现就急性放射性粘膜炎的发生机理及防治在现代医学和传统医学方面的进展作一综述。     

放射性肠损伤的支持治疗进展

接受腹盆腔放疗的患者有一定程度放射性肠损伤的发生,损伤部位可以累及小肠、结肠和直肠,主要表现为腹痛、腹泻、便血、里急后重、梗阻等,大多数为轻度症状,可以自行缓解,少数严重者明显影响生存质量。现代精确放疗一定程度上减轻了不良反应,但是仍无法完全预防,且目前尚无特效的治疗用药,治疗上以对症治疗和支持治疗为主,如止痛、止泻、抗炎和黏膜保护剂灌肠等药物对症治疗;菌群移植也可在一定程度上缓解症状,同时需要营养支持和心理干预的支持等。本文对放射性肠损伤在目前国内外的支持治疗的最新研究进行总结,为临床应用提供参考,以期为今后的研究方案提供指导。      

宫颈癌盆腔放疗致急性放射性肠炎的临床观察

目的：总结宫颈癌盆腔放射治疗导致急性放射性肠炎的发生规律及防治方法。方法：回顾性分析行盆腔放疗的97例宫颈癌患者，分析腹痛、腹泻症状出现的时间及程度，评价急性放射性肠炎的分级，对比放疗前后血象和KPS的变化情况。结果：急性放射性肠炎多发生在放疗后1周至1个月内，Ⅰ度发生率为41％，Ⅱ度发生率15％，Ⅲ度发生率2％，总发生率为58％；放疗后患者WBC值平均下降23％，PLT值平均下降18％；46％的患者放疗后KPS下降。结论：宫颈癌盆腔放疗患者急性放射性肠炎发生率较高，应引起临床足够重视。     

腹、盆腔肿瘤放疗后急性放射性肠道损伤的剂量学因素分析

目的：探讨腹、盆腔肿瘤患者接受调强放射治疗（IMRT）后出现≥2级急性放射性肠道损伤与患者临床特征参数及小肠（small bowel,SB）剂量体积参数的相关性。方法：回顾分析63例接受 IMRT 的腹、盆腔肿瘤患者资料,应用 CTCAE 3．0评分标准对患者急性放射性肠道损伤进行评价分级,分析患者临床特征参数及小肠受照的剂量体积参数（Dmax、Dmin、Dmean、D2cc、D5cc及小肠接受的 V5～60的绝对体积）与急性放射性肠道损伤发生的相关性。结果：所有患者 IMRT 后在急性观察期内,发生≥2级急性放射性肠道损伤13例,发生率为20．63％（13／63）。单因素分析发现小肠 V20～60、D2cc、D5cc 与≥2级急性放射性肠道损伤的发生相关。多因素分析发现小肠的 V20、V55是≥2级急性放射性肠道损伤发生的独立影响因素（P ＝0．025和0．004）。V20＝183cm3、V55＝2cm3可看作小肠的放射耐受剂量,其对≥2级急性放射性肠道损伤预测的灵敏度均为0．846,特异度分别为0．800、0．960。结论：对于行 IMRT 治疗后的腹、盆腔肿瘤患者,小肠的 V20、V55是预测≥2级急性放射性肠道损伤有独特意义的影响因素。     

用影像引导提高乳腺癌调强放射治疗精度

目的 力求说明与IGRT有关的临床和技术问题,以及这些问题与乳腺癌病人的标准治疗方案的相关知识。方法 使用医科达SynergyTM的锥形束CT(CBCT)对32例乳腺癌患者进行治疗前扫描,通过IGRT技术对32例患者进行调强放疗。每次放疗前用CBCT校正射野偏差,其偏差由XVI上的CBCT图像与计划螺旋CT图像匹配在左右、头脚、前后方向上得出,根据误差调整治疗床位置后治疗,并评价急性放射性皮肤反应、急性放射性肺损伤及急性放射性心脏损伤。结果 32例乳腺癌患者治疗前CBCT扫描采集的图像与计划参考图像比较在左右、头脚、前后方向上平均误差分别为0.32cm、0.23cm、-0.44cm;调整治疗床后3个方向的平均误差分别为0.08cm、-0.06cm、-0.13cm。放疗后一个月急性皮肤反应为0级23例、1级9例,无急性放射性肺损伤及心脏损伤的病例出现。结论 目前调强放疗是满足乳腺癌临床要求的最佳计划,IGRT的辅助能够提高乳腺癌放疗精度。     

骨髓间充质干细胞治疗放射性肺损伤的研究进展

放射性肺损伤后期表现为肺纤维化,临床反应重,常导致放疗患者呼吸衰竭而死亡。目前尚无理想的治疗方法。骨髓间充质干细胞具有自我更新及多向分化潜能,可以归巢到受损的肺部,通过诱导分化进行组织修复,有可能使其成为治疗放射性肺损伤的有力手段。     

Prévention médicale et traitement des complications pulmonaires secondaires à la radiothérapie

Radiation-induced lung injuries mainly include the (acute or sub-acute) radiation pneumonitis, the lung fibrosis and the bronchiolitis obliterans organizing pneumonia (BOOP). The present review aims at describing the diagnostic process, the current physiopathological knowledge, and the available (non dosimetric) preventive and curative treatments. Radiation-induced lung injury is a diagnosis of exclusion, since clinical, radiological, or biological pathognomonic evidences do not exist. Investigations should necessarily include a thoracic high resolution CT-scan and lung function tests with a diffusing capacity of the lung for carbon monoxide. No treatment ever really showed efficacy to prevent acute radiation-induced lung injury, or to treat radiation-induced lung fibrosis. The most promising drugs in order to prevent radiation-induced lung injury are amifostine, angiotensin-converting-enzyme inhibitors and pentoxifylline. Inhibitors of collagen synthesis are currently tested at a pre-clinical stage to limit the radiation-induced lung fibrosis. Regarding available treatments of radiation-induced pneumonitis, corticoids can be considered the cornerstone. However, no standardized program or guidelines concerning the initial dose and the gradual tapering have been scientifically established. Alternative treatments can be prescribed, based on clinical cases reporting on the efficacy of immunosuppressive drugs. Such data highlight the major role of the lung dosimetric protection in order to efficiently prevent radiation-induced lung injury.     

Pharmacological modulation of radiation-induced oral mucosal complications

Radiation-induced mucositis is a common toxicity, especially in patients with head and neck cancers. Despite recent technological advances in radiation therapy, such as intensity-modulated radiotherapy, radiation-induced mucositis is still causing treatment disruptions, negatively affecting patients’ long and short term quality of life, and impacting medical resources use with economic consequences. The objective of this article was to review the latest updates in the management of radiation-induced mucositis, with a focus on pharmaceutical strategies for the prevention or treatment of mucositis. Although numerous studies analysing the prevention and management of oral radiation-induced mucositis have been conducted, there are still few reliable data to guide daily clinical practice. Furthermore, most of the tested drugs have shown no (anti-inflammatory cytokine, growth factors) or limited (palifermin) effect. Therapies for acute oral mucositis are predominantly focused on improving oral hygiene and providing symptoms control. Although low-level laser therapy proved efficient in preventing radiation-induced oral mucositis in patients with head and neck cancer, this intervention requires equipment and trained medical staff, and is therefore insufficiently developed in clinical routine. New effective pharmacological agents able to prevent or reverse radio-induced mucositis are required.     

Glucagon-like peptide-2 improves both acute and late experimental radiation enteritis in the rat

PURPOSE: Acute and/or chronic radiation enteritis can develop after radiotherapy for pelvic cancers. Experimental and clinical observations have provided evidence of a role played by acute mucosal disruption in the appearance of late effects. The therapeutic potential of acute administration of glucagon-like peptide-2 (GLP-2) against acute and chronic intestinal injury was investigated in this study. METHODS AND MATERIALS: Intestinal segments were surgically exteriorized and exposed to 16.7 or 19 Gy X-rays. The rats were treated once daily with vehicle or a protease-resistant GLP-2 derivative for 14 days before irradiation, with or without 7 days of GLP-2 after treatment. Macroscopic and microscopic observations were made 2 and 15 weeks after radiation exposure. RESULTS: In the control animals, GLP-2 induced an increase in intestinal mucosal mass, along with an increase in villus height and crypt depth. GLP-2 administration before and after irradiation completely prevented the acute radiation-induced mucosal ulcerations observed after exposure to 16.7 Gy. GLP-2 treatment strikingly reduced the late radiation damage observed after 19 Gy irradiation. Microscopic observations revealed an improved organization of the intestinal wall and an efficient wound healing process, especially in the smooth muscle layers. CONCLUSION: GLP-2 has a clear therapeutic potential against both acute and chronic radiation enteritis. This therapeutic effect is mediated through an increased mucosal mass before tissue injury and the stimulation of still unknown mechanisms of tissue response to radiation damage. Although these preliminary results still need to be confirmed, GLP-2 might be a way to limit patient discomfort during radiotherapy and reduce the risk of consequential late effects.     

Probiotics and Health

Probiotics are described as live microbial food ingredients that are beneficial to health of the of host, especially ‍by improving intestinal microbial balance. The major consumption of probiotics is in dairy-based foods form, which ‍is containing intestinal species of Lactobacillus and Bifidobacterium. A number of potential benefits of probiotics ‍have been proposed, including: adherence to cells; exclusion or reduction of pathogenic adherence; production of ‍acids, hydrogen peroxide, and bacteriocins antagonistic to pathogen growth; safe, noninvasive, noncarcinogenic and ‍nonpathogenic characteristics; and congregation to form a normal balanced flora. The interrelation between probiotics ‍and health are reviewed in this article.     

Effects of probiotic Lactobacillus casei DN-114 001 in prevention of radiation-induced diarrhea: results from multicenter, randomized, placebo-controlled nutritional trial

PURPOSE: To determine whether a probiotic drink containing Lactobacillus casei DN-114 001 reduces the incidence of radiation-induced diarrhea in patients with gynecologic cancer. METHODS AND MATERIALS: Patients who were undergoing pelvic radiotherapy (45-50 Gy, conventional fractionation) for either cervical carcinoma (radiotherapy and weekly cisplatin) or endometrial adenocarcinoma (postoperative radiotherapy) were randomly assigned to a probiotic drink or placebo, in a double-blind fashion. The probiotic drink consisted of liquid yogurt containing L. casei DN-114 001 at 10(8) CFU/g. The patients recorded the daily the number of bowel movements and scored the stool consistency using the Bristol scale. Diarrhea was graded weekly according the Common Toxicity Criteria system. The primary endpoint was to reduce the incidence of diarrhea, defined by a Common Toxicity Criteria Grade of 2 or greater or the need for loperamide. RESULTS: A total of 85 patients were enrolled. Grade 2 or greater diarrhea and/or the use of loperamide was observed in 24 of 41 patients in the placebo group and 30 of 44 in the probiotic group (p = 0.568). No differences were found in the median time to the presentation of the primary endpoint. Probiotic intervention had a significant effect on stool consistency (p = 0.04). The median time for patients to present with Bristol scale stools of Type 6 or greater was 14 days for patients receiving the probiotic drink vs. 10 days for those receiving placebo. CONCLUSION: Nutritional intervention with the probiotic drink containing L. casei DN-114 001 does not reduce the incidence of radiation-induced diarrhea as defined by a Common Toxicity Criteria Grade 2 or greater. However, it had a significant effect on stool consistency as measured by the Bristol scale.     

人体微生态与放疗之间的相互关系

人体微生态,尤其肠道菌群是人体一个新的动态器官,菌群及其代谢物可直接作用于肠道或间接通过菌群-肠-器官轴作用全身组织器官而发挥着重要作用.人体微生态的主要生理作用包括:调节胃肠道运动和消化、肠道屏障,调节免疫稳态和炎症反应、物质代谢、细胞分化和周转,以及认知行为等.肿瘤放疗可引起人体菌群的明显改变,表现为菌群多样性和丰...     

谷氨酰胺预防和治疗射线诱导急性腹泻的疗效观察

目的 探讨静脉补充谷氨酰胺对子宫恶性肿瘤术后放疗引起的急性腹泻的预防和治疗作用。方法将63例子宫恶性肿瘤术后患者分为对照组和治疗组,仅治疗组于放疗第4周（第22天）静脉补充谷氨酰胺100ml,每天1次,共10次;分析两组急性腹泻的发生率、严重程度及止泻药物的使用频率和剂量。结果治疗组和对照组的急性腹泻发生率分别为87.1％和90.6％,组间差异无统计学意义（P＞0.05）。治疗组和对照组平均每天腹泻次书分别为2.6次和3.0次,差异无统计学意义（P＞0.05）;第5周治疗组平均每天腹泻次数少于对照组,差异有统计学意义（P＜0.05）。治疗组复方苯乙哌啶的使用率和平均使用剂量均少于对照组（P＜0.05）。结论 放疗期间静脉补充谷氨酰胺对射线诱导的急性腹泻具有一定的治疗作用,但能否预防急性腹泻尚需进一步研究。     

Bilateral phrenic nerve dysfunction: a late complication of mantle radiation

Neurologic complications from radiotherapy can be immediate or can occur many years after treatment. A known complication of radiotherapy to the supraclavicular and axillary lymph nodes is brachial plexus neuropathy. Although not a common injury, phrenic nerve dysfunction has been reported in association with radiation-induced brachial neuropathy. We describe a patient who developed asymmetric diaphragmatic weakness secondary to phrenic nerve paralysis 37 years after receiving mantle radiation for Hodgkin lymphoma. The patient did not have an associated brachial plexus neuropathy or a secondary malignancy involving the phrenic nerves. A radiation-induced injury was the most likely cause.     

The effect of oral sucralfate on the acute proctitis associated with prostate radiotherapy: a double-blind, randomized trial

PURPOSE: Acute rectal complications occur in the majority of patients receiving external-beam radiotherapy for carcinoma of the prostate. Sucralfate has been proposed to reduce radiation-induced mucosal injury by forming a protective barrier on ulcer bases, binding local growth factors, and stimulating angiogenesis. However, there is conflicting clinical evidence as to whether sucralfate, taken prophylactically during radiotherapy, can ameliorate the symptoms of acute radiation proctitis. METHODS AND MATERIALS: A double-blind randomized trial was conducted at four Radiation Oncology Departments in Sydney, Australia, between February 1995 and June 1997. A total of 338 patients with clinically localized prostate cancer receiving small volume radiotherapy, of whom 335 were evaluable, were randomized to receive either 3 g of oral sucralfate suspension or placebo twice a day during radiotherapy. Patients kept a daily record of their bowel symptoms and were graded according to the RTOG/EORTC acute toxicity criteria. RESULTS: One hundred sixty-four patients received sucralfate and 171 received placebo. Both groups were well balanced with regard to patient, tumor, treatment factors, and baseline symptoms, except that the placebo group had a significantly more liquid baseline stool consistency score (p = 0.004). Patients kept a daily diary of symptoms during radiotherapy. After adjusting for baseline values, there was no significant difference between the two groups with regard to stool frequency (p = 0.41), consistency (p = 0.20), flatus (p = 0.25), mucus (p = 0.54), and pain (p = 0.73). However, there was more bleeding in the sucralfate group, with 64% of patients noticing rectal bleeding, compared with 47% in the placebo group (p = 0.001). There was no significant difference between the two groups with respect to RTOG/EORTC acute toxicity (p = 0.88; sucralfate 13%, 44%, 43% and placebo 15%, 44%, 40% for grade 0, 1, and 2, respectively). CONCLUSION: This study suggests that oral sucralfate taken prophylactically during radiotherapy does not ameliorate the symptoms of acute radiation proctitis and may increase acute bleeding. The cause of the increased bleeding in the sucralfate group is unclear. As the pathogenesis of acute and late reactions are different, late follow-up, which includes sigmoidoscopic evaluation, is currently being performed on this cohort of patients.