The role of probiotics in gastrointestinal disease.

Patients with intestinal failure often have diarrhea for a variety of reasons. Treatment of diarrhea has centered on the use of antidiarrheal medications and antibiotic therapy. Recently, there has been interest in the oral administration of probiotics for these patients with small bowel bacterial overgrowth, inflammatory bowel disease, and radiation enteritis. This paper reviews the studies that have used probiotics to treat patients with short bowel syndrome and gastrointestinal disorders. Additionally, some of the specific issues regarding probiotics are addressed.     

长春瑞滨联合顺铂治疗晚期乳腺癌的疗效及毒副反应观察

[目的]观察长春瑞滨（盖诺）联合顺铂化疗方案治疗晚期乳腺癌的近期临床疗效与毒副反应。[方法]运用盖诺＋顺铂联合化疗方案治疗晚期乳腺癌共40例，连续治疗2周期后评价疗效与毒副作用，疗效及毒性判断参照WHO标准。[结果]有效率为55．0％，其中CR（完全缓解）1例，PR（部分缓解）21例，SD（稳定）13例，PD（进展）5例。主要毒副反应为胃肠道反应和骨髓抑制。[结论]长春瑞滨联合顺铂化疗方案对晚期乳腺癌有较好的疗效。毒副反应可以耐受，可作为晚期乳腺癌患者的二线治疗方案，值得临床推广。     

Probiotics as functional food in the treatment of diarrhea

PURPOSE OF REVIEW: A disturbance in microbial balance of the gastrointestinal tract is often associated with diarrhea. Therefore, probiotics, as beneficial microorganisms for host health, have attracted clinical attention for their potential therapeutic application in the treatment of diarrhea. This review focuses on new research findings relevant to the effects of probiotics on diarrhea prevention and treatment and potential mechanisms of action for this alternative therapy for diarrhea. RECENT FINDINGS: Clinical trials suggest potential beneficial effects of probiotic therapy for preventing and treating antibiotic-associated diarrhea, acute diarrhea including rotavirus-induced diarrhea, traveler's diarrhea, and diarrhea-predominant irritable bowel syndrome. The most extensively studied probiotics for diarrhea are Lactobacillus, Bifidobacterium and Saccharomyces, with potential mechanisms of therapeutic action based on the protection of intestinal epithelial cell and barrier function, prevention of enterotoxin binding to intestinal epithelial cells, and regulation of intestinal microbial environment. SUMMARY: Growing evidence suggests that probiotics may serve as a functional food in the treatment of diarrhea. Remaining challenges include identifying mechanisms of action to provide the basis of more refined hypothesis-driven clinical trials. The correct combination and concentration of probiotics applied to the appropriate gastrointestinal disorders may improve the efficacy of this approach for diarrhea and other diseases.     

谷氨酰胺预防新辅助化疗导致肠道损伤的前瞻性、随机研究

目的 :观察口服谷氨酰胺对化疗导致肠道损伤的保护作用。　方法 :本研究为前瞻性随机研究。将接受新辅助化疗的 39例乳腺癌病人随机分为两组。对照组 (n =2 0 )化疗时不口服谷氨酰胺 ;实验组 (n =19)化疗同时口服谷氨酰胺 (30 g/d) ,两组病人均行CEF(环磷酰胺 ,表阿霉素 ,5 FU)方案化疗。化疗前和化疗后观察并记录化疗不良反应 ,测定血浆谷氨酰胺浓度和肠道通透性。　结果 :化疗后实验组血浆谷氨酰胺浓度明显高于对照组 ,为(4 15 .4 5± 6 8.0 1)mmol/Lvs (30 2 .83± 5 1.98)mmol/L(P <0 .0 5 ) ;而肠道通透性增加明显低于实验组 ,为 0 .0 4 93± 0 .0 0 94vs 0 .0 6 31± 0 .0 12 0 (P <0 .0 5 ) ,两组病人毒性、口腔炎、腹泻及化疗后肿瘤体积变化均无显著差异。　结论 :口服谷氨酰胺能够减轻化疗导致的乳腺癌病人肠道通透性增加 ,但对化疗引起的毒性、口腔炎和腹泻等不良反应无保护作用 ,口服谷氨酰胺也不影响肿瘤对新辅助化疗的反应。     

Probiotics and their potential health claims

Many studies have attempted to identify specific positive health effects of probiotics. One of the challenges in generalizing health effects of probiotics is that different strains exert disparate effects on human health. As a result, the efficacy of one strain or species cannot necessarily be inferred from another. The objective of this review is to examine the current scientific literature that could be used as the basis for potential health claims. More specifically, this paper will review existing evidence of different probiotic strains to prevent and treat diarrhea, treat irritable bowel syndrome (IBS), treat inflammatory bowel disease, and prevent colon cancer. The strongest evidence is related to the use of Lactobacillus rhamnosus GG in the prevention and treatment of rotavirus-associated diarrhea. Further examination of the literature also shows promise in the treatment of some forms of IBS with probiotics. Future studies that use consistent supplementation regimes will allow more definitive conclusions to be drawn on the effects of probiotics on IBS, inflammatory bowel disease, and colon cancer.     

Nutrition modulation of gastrointestinal toxicity related to cancer chemotherapy: from preclinical findings to clinical strategy

Chemotherapy‐induced gut toxicity is a major dose‐limiting toxicity for many anticancer drugs. Gastrointestinal (GI) complications compromise the efficacy of chemotherapy, promote overall malnutrition, aggravate cancer cachexia, and may contribute to worsened prognosis. The GI tract is an attractive target for nutrition modulation, owing to its direct exposure to the diet, participation in uptake and metabolism of nutrients, high rate of cell turnover, and plasticity to nutrition stimuli. Glutamine, ω‐3 polyunsaturated fatty acids, and probiotics/prebiotics are therapeutic factors that potentially modulate GI toxicity related to cancer treatments. Preclinical and clinical evidence are reviewed to critically define plausible benefits of these factors and their potential development into adjuncts to cancer chemotherapy. Mechanisms underlying the action of these nutrients are being unraveled in the laboratory. Optimal strategies to translate these findings into clinical care still remain to be elucidated. Key questions that remain to be answered include the following: which nutrient or combination of nutrients is selected for which patient and chemotherapy regimen? What mechanisms are responsible for modulation, and how are nutrient(s) administered in a clinically optimal manner? Research exploring interactions between different nutrients in GI protection is ongoing and demands further understanding. How nutrition preparations given to chemotherapy‐treated patients are formulated in terms of component selection and dose optimization should be carefully studied and justified.     

The hematopoietic growth factor GM-CSF in chemotherapy for advanced breast carcinoma

A non-randomized study was carried out in the Free University Hospital, Amsterdam, to investigate the (hematologic) toxicity and antitumor response of patients with advanced breast cancer treated with intensive chemotherapy in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF). Of 11 patients with an inoperable or metastasized breast cancer, 5 were treated with doxorubicin 75 mg/m2 + cyclophosphamide 750 mg/m2 intravenously every 3 weeks and 6 patients with 90 and 1000 mg/m2 respectively. When in a preceding cycle a significant hematologic toxicity was observed, this patient was treated in the subsequent cycle with the same dose of chemotherapy in combination with GM-CSF 250 micrograms/m2/day from day 2-12 as a continuous infusion. Bone marrow depression was diminished in the presence of GM-CSF. This was apparent from a milder decline of the number of neutrophilic granulocytes, reduction of the neutropenic period and a more rapid recovery of the neutrophil number. A transient eosinophilia and a mild monocytosis were also observed. GM-CSF did not improve erythrocyte and thrombocyte counts. The efficacy of GM-CSF was less pronounced in the group of patients with the highest dose of chemotherapy. GM-CSF was associated with malaise, fever and a small decrease of blood pressure, which in combination with a frequently occurring anemia and the side-effects of high dose chemotherapy, resulted in a substantial toxicity. In 9/11 patients an objective tumor regression was noted. GM-CSF stimulated the recovery of granulocytes after intensive chemotherapy. Treatment of a small group of patients with advanced breast cancer with intensive chemotherapy resulted in a high antitumor response.     

Comment On: Probiotic Prophylaxis in Predicted Severe Acute Pancreatitis: A Randomized,Double‐Blind,Placebo‐Controlled Trial

BACKGROUND: Infectious complications and associated mortality are a major concern in acute pancreatitis. Enteral administration of probiotics could prevent infectious complications, but convincing evidence is scarce. Our aim was to assess the effects of probiotic prophylaxis in patients with predicted severe acute pancreatitis. METHODS: In this multicentre randomised, double‐blind, placebo‐controlled trial, 298 patients with predicted severe acute pancreatitis (Acute Physiology and Chronic health Evaluation [APACHE II] score > or =8, Imrie score > or =3, or C‐reactive protein >150 mg/L) were randomly assigned within 72 h of onset of symptoms to receive a multispecies probiotic preparation (n = 153) or placebo (n = 145), administered enterally twice daily for 28 days. The primary endpoint was the composite of infectious complications—ie, infected pancreatic necrosis, bacteraemia, pneumonia, urosepsis, or infected ascites—during admission and 90‐day follow‐up. Analyses were by intention to treat. This study is registered, number ISRCTN38327949. FINDINGS: One person in each group was excluded from analyses because of incorrect diagnoses of pancreatitis; thus, 152 individuals in the probiotics group and 144 in the placebo group were analysed. Groups were much the same at baseline in terms of patients' characteristics and disease severity. Infectious complications occurred in 46 (30%) patients in the probiotics group and 41 (28%) of those in the placebo group (relative risk 1.06, 95% CI 0.75‐1.51). 24 (16%) patients in the probiotics group died, compared with nine (6%) in the placebo group (relative risk 2.53, 95% CI 1.22‐5.25). Nine patients in the probiotics group developed bowel ischaemia (eight with fatal outcome), compared with none in the placebo group (p = 0.004). INTERPRETATION: In patients with predicted severe acute pancreatitis, probiotic prophylaxis with this combination of probiotic strains did not reduce the risk of infectious complications and was associated with an increased risk of mortality. Probiotic prophylaxis should therefore not be administered in this category of patients. (Lancet. 2008;371:651‐659) Besselink MG, van Santvoort HC, Buskens E, et al; Dutch Acute Pancreatitis Study Group     

Prebiotics and probiotics for gastrointestinal health

Accumulating research evidence suggests that probiotics and prebiotics, which both influence the endogenous flora, may have a role in human therapies, especially in the prevention of digestive diseases. This article summarises the current knowledge on their fate in the gastrointestinal tract (survival, adherence, colonization, or metabolism), mechanisms of action, potential adverse effects and proven effects. It presents and comments on the results of randomized controlled trials using various probiotics to treat lactose intolerance, antibiotic associated diarrhoea, gastroenteritis, intestinal infections and colonization by pathogenic bacteria, and inflammatory bowel disease. Finally, the results of randomized controlled trials that used prebiotics to treat constipation and hepatic encephalopathy are also discussed, as well as potential applications, especially colon cancer prevention.     

Emerging Roles of Probiotics in Prevention and Treatment of Breast Cancer: A Comprehensive Review of Their Therapeutic Potential

Breast cancer is the most common cancer among women. Need for novel preventive and curative approaches with more safety than the present one seems inevitable. This review is devoted to potentially favorable role of probiotics in prevention and treatment of breast cancer as well as their alleviating role regarding chemotherapy-induced side effects. Literature was searched for human, animal, and in vitro studies about the role of probiotics in breast cancer. In vitro studies showed that probiotic intervention induces cancer cells apoptosis and inhibits their proliferation. In animal models, treatment with probiotics inhibited tumor growth and reduced tumor size; also, the immunomodulatory, antiangiogenesis and antimetastatic activities of probiotics were illustrated. Human studies showed that intake of Lactobacillus casei shirota reduced the breast cancer incidence and consumption of fermented milk products and yogurt was inversely associated with breast cancer incidence; however, no study regarding the curative role of probiotics in breast cancer is available. Studies on the effect of probiotics on chemotherapy-induced side effects in breast cancer were contradictory but showed potential for more investigation. Probiotics seem to have a potential role in both prevention and treatment of breast cancer. However, more clinical studies are needed to elucidate their efficacy and safety.     

乳腺癌患者76例围手术期护理体会

目的 做好乳腺癌患者围手术期的护理工作,使乳腺癌患者顺利渡过手术治疗及放化疗,为控制肿瘤复发、延长生命得到保障.方法 选择笔者所在医院2007年1月～2009年1月收治的75例乳腺癌患者,采取一系列的围手术期的护理措施.结果 所有病例均采用手术治疗和全身化疗相结合的综合治疗方法.行乳腺癌根治切除术35例,占46.7%;行乳腺癌改良根治切除术,40例,占53.3%.结论 通过采取一系列的围手术期的护理措施,乳腺癌患者减轻了心理负担,增强了战胜疾病的信心,积极配合手术、化疗、放疗等,提高了治愈率.     

The application of probiotics in cancer

Lactic acid bacteria (LAB) are present in many foods such as yoghurt and are frequently used as probiotics to favour some biological functions in the host. Many investigators have evaluated the therapeutic effects of yoghurt and LAB commonly used in yoghurt production against diseases such as cancer, infection, and gastrointestinal disorders. The increase of immune cell activity in the prevention of cancer by LAB consumption has also been described. Another possible explanation for the preventive effect of probiotics on carcinogenesis is their effect on other bacteria in the intestine. Probiotics may suppress the growth of bacteria that convert procarcinogens into carcinogens, thereby reducing the amount of carcinogens in the intestine. The present review is focused on two types of cancer in which milk fermented by LAB may show a beneficial effect: colon cancer and breast cancer.     

Probiotics and medical nutrition therapy.

Probiotics have been defined by The Food Agricultural Organization/World Health Organization (FAO/WHO) as "live microorganisms which when administered in adequate amounts confer a health benefit to the host." They have been used for centuries in the form of dairy-based fermented products, but the potential use of probiotics as a form of medical nutrition therapy has not received formal recognition. A detailed literature review (from 1950 through February 2004) of English-language articles was undertaken to find articles showing a relationship between probiotic use and medical conditions. Medical conditions that have been reportedly treated or have the potential to be treated with probiotics include diarrhea, gastroenteritis, irritable bowel syndrome, and inflammatory bowel disease (Crohn's disease and ulcerative colitis), cancer, depressed immune function, inadequate lactase digestion, infant allergies, failure-to-thrive, hyperlipidemia, hepatic diseases, Helicobacter pylori infections, genitourinary tract infections, and others. The use of probiotics should be further investigated for possible benefits and side-effects in patients affected by these medical conditions.     

卡培他滨治疗晚期结直肠癌发生手足综合征与疗效的观察

目的探讨含卡培他滨联合方案一线治疗不可切除晚期结直肠癌所致手足综合征的发生率及与疗效的关系。方法回顾性分析我科39例使用含卡培他滨双药联合方案一线治疗晚期结直肠癌的临床资料．其中32例接受卡培他滨加奥沙利铂化疗,7例使用卡培他滨加伊立替康化疗。结果39例患者中发生1度、2度和3度手足综合征分别占35．9％、17．9％和7．7％,出现手足综合征的客观有效率为45．8％;未出现手足综合征病例的客观有效率为13．3％,P=0．024;疾病控制率分别为75％和40％,有改善疾病控制的趋势,P=O．065。结论手足综合征是卡培他滨治疗结直肠癌的主要剂量限制性毒性,出现HFS者提示有效率可能增大．但需要更多的临床研究进一步验证。     

The Potential Role of Probiotics in Cancer Prevention and Treatment

The human gut microbiota has a significant effect on many aspects of human physiology such as metabolism, nutrient absorption, and immune function. Imbalance of the microbiota has been implicated in many disorders including inflammatory bowel disease, obesity, asthma, psychiatric illnesses, and cancers. As a kind of functional foods, probiotics have been shown to play a protective role against cancer development in animal models. Clinical application of probiotics indicated that some probiotic strains could diminish the incidence of postoperative inflammation in cancer patients. Chemotherapy or radiotherapy-related diarrhea was relieved in patients who were administered oral probiotics. The present review summarizes the up-to-date studies on probiotic effects and the underlying mechanisms related to cancer. At present, it is commonly accepted that most commercial probiotic products are generally safe and can improve the health of the host. By modulating intestinal microbiota and immune response, some strains of probiotics can be used as an adjuvant for cancer prevention or/and treatment.     

Development and evaluation of a decision aid for patients considering first-line chemotherapy for metastatic breast cancer

Objective Treatment decisions in advanced breast cancer are complex, with enhanced quality of life and survival among important treatment goals. Patients with metastatic breast cancer face the decision of whether or not to have chemotherapy, and many wish to be involved in this decision. We report the development and evaluation of a decision aid (DA) designed to assist patients facing this treatment decision. Design and sample Women with metastatic breast cancer (n = 17) and medical oncologists in Australia and Canada (n = 7) were invited to evaluate the DA. Intervention A DA was developed for patients with hormone‐resistant metastatic breast cancer considering chemotherapy. The DA presented options of supportive care, with or without chemotherapy. Potential benefits and side effects of different chemotherapy regimens, and evidence‐based prognostic estimates were described, and a values clarification exercise included. Main outcome measures Patient questionnaires evaluating information and decision involvement preferences, attitudes toward the DA and oncologist feedback regarding attitudes toward the DA. Results Seventeen patients participated; fifteen desired as much information about their illness as possible; sixteen wished to be actively involved in the decision‐making process. The majority rated the DA as highly acceptable, clear and informative, and would recommend it to others facing this treatment decision. Conclusion This is the first DA for patients with advanced metastatic breast cancer considering chemotherapy. A randomized trial is underway to evaluate its role in clinical decision‐making.     

Impact of fatigue on quality of life among breast cancer patients receiving chemotherapy

ObjectivesFatigue is the most frequently reported symptom experienced by cancer patients and has a profound effect on their quality of life (QOL). The study aimed to determine the impact of fatigue on QOL among breast cancer patients receiving chemotherapy and to identify the risk factors associated with severe fatigue incidence.MethodsThis was an observational prospective study carried out at multiple centers. In total, 172 breast cancer patients were included. The Functional Assessment of Chronic Illness Therapy-Fatigue Questionnaire was used to measure QOL, while the Brief Fatigue Inventory (BFI) was used to assess the severity of fatigue.ResultsThe total average mean and standard deviation of QOL were 84.58±18.07 and 4.65±1.14 for BFI scores, respectively. A significant association between fatigue and QOL was found in linear and multiple regression analyses. The relationships between fatigue severity and cancer stage, chemotherapy dose delay, dose reduction, chemotherapy regimen, and ethnicity were determined using binary logistic regression analysis.ConclusionThe findings of this study are believed to be useful for helping oncologists effectively evaluate, monitor, and treat fatigue related to QOL changes.     

The SYNCAN project: goals, set-up, first results and settings of the human intervention study

Experimental evidence on the anticancer properties of dietary prebiotics such as chicory inulin and oligofructose and dietary probiotics has accumulated in recent years. Various experimental models ranging from chemoprevention studies, tumour implantation models to genetically modified mice models, etc. have systematically shown the protective effects of these food ingredients. In some studies it appeared that synbiotics (combination of pre- and probiotics) exerted synergistic activity against processes of carcinogenesis. The logical next step in research was to find out if these observations also would be valid for human volunteers. This was the principal goal of the EU-sponsored SYNCAN project (QLK1-1999-346) which involved the integration of an in vitro study to select the most suitable synbiotic preparation, the application of this synbiotic in an in vivo rat model of chemically induced colon cancer, and, as the heart of the project, the investigation of the synbiotic effects in a human intervention study. The in vitro tests consisted of fermentation studies where the interaction of pre- and probiotics was studied. Cell-free supernatants were generated from various synbiotic combinations fermented by faecal slurry, which were then used to optimise a series of bioassays. In the rat study the anticarcinogenic effect of prebiotics and synbiotics but not of probiotics was demonstrated. Using tissue samples generated in this model, attempts were made to gain a better insight into the mechanisms underlying cancer development. The human intervention study consisted of two groups of volunteers. One group was composed of people at high risk (polypectomised subjects) for colon cancer and the other of volunteers (colon cancer subjects) who had previously undergone 'curative resection' for colon cancer but were not currently receiving treatment. The present paper describes the experimental design of the SYNCAN study, and demonstrates a functional effect of the synbiotic preparation (probiotic survival during gastrointestinal transit and modification of the intestinal flora). Detailed experimental outcome of the human intervention study will be reported elsewhere.     

The Impact of Multispecies Probiotics on Calcium and Magnesium Status in Healthy Male Rats

Although probiotics have been discovered in numerous diseases in the last decade, there is little consensus on the relationship between probiotic properties and minerals balance and their distribution in the organism. This research aimed to evaluate the calcium (Ca) and magnesium (Mg) status in rats on a diet containing multispecies probiotics. Thirty male 10-week-old Wistar rats were selected and divided into three groups (n = 10 rats)—a group fed a standard diet (C), a group fed a low-dose of multispecies probiotics with 2.5 × 10⁹ CFU per day (LD), and a group fed high-dose of multispecies probiotics 1 × 10¹⁰ CFU per day (HD) for 6 weeks. The results revealed that HD intake significantly increased the Ca concentration in hair and Mg concentration in femur bones. A significant positive correlation was found between calcium and magnesium levels in hair. The Ca/Mg molar ratio was lower in testicles in the groups with probiotics. In conclusion, multispecies probiotics altered the Ca concentration in hair and Mg level in femur bone, and also changed the molar ratio of these elements in testicles in male rats.     

三阴性乳腺癌的活化T细胞免疫表型与免疫治疗疗效的临床研究

目的探讨复发转移三阴性乳腺癌与非三阴性乳腺癌活化T细胞免疫表型的差异及意义,并观察化疗联合胸腺肽α1与单独化疗相比对三阴性乳腺癌生存影响的差异。方法对60例复发转移的三阴性乳腺癌患者,测定活化T细胞免疫表型,与非三阴乳腺癌患者活化T细胞免疫表型比较。60例随机分为两组,A组给予化疗联合免疫增强剂治疗,胸腺肽α1 1．6mg,每周二次,共3个月;B组单独化疗,（两组化疗方案相似TX,TAorTE,NP,GP）,比较两组的ORR（有效率）,PFS（无疾病进展时间）,总生存期（0S）及生活质量KPS评分。结粟三阴性乳腺癌患者活化T细胞免疫表型结果明显低于非三阴性乳腺癌患者,有显著性统计学意义（P〈0．05）。三阴性乳腺癌给予免疫增强剂胸腺肽α1加化疗组与单独化疗组相比,两组的ORR（总有效率）：A组27例（63．0％）和B组21例（51．6％）,比较无明显统计学意义,而CR17例（29．7％）比10例（16．6％）,P〈0．001,有明显统计学意义。PFS（无疾病进展时间）两组12月比7月,A组优于对照组,P〈0．05,有明显的统计学意义。一年总生存期（0S）两组无明显统计差异。症状体征的生活质量改善,A组KPS提高,明显优于对照组（P〈0．01）。结论三阴性乳腺癌患者活化T细胞免疫表型明显低于非三阴性乳腺癌患者,免疫功能低下,预后差。免疫增强剂胸腺肽α1可提高三阴性乳腺癌患者ORR（总有效率）,CR率及PFS（无疾病进展时间）,并可提高患者生活质量,值得临床进一步推广应用。