Nutritional status and endocrine response to hemorrhage

Hyperglycemia-inducing hyperosmolality has recently been proven beneficial in the maintenance of blood volume and extracellular fluid volume during early hemorrhagic hypotension. Fed animals benefitted from better plasma refill compared with starved ones when subjected to equal blood loss. Using lightly sedated fed and 24-30 h starved rats, hormones with relevance to glucose homeostasis were studied during 90 min of hemorrhagic hypotension of 70 mmHg (1 mmHg = 133.32 Pa). Marked differences in the overall hormonal developments were found between the two groups. In fed rats, insulin and glucagon responses were initially attenuated, while somatostatin increased to an early peak level at 30 min, returning to basal at 90 min. In starved rats, somatostatin increased gradually during the 90 min. Adrenaline release was massive in both groups. Corticosterone showed no increase from basal levels in the fed group during hemorrhage, while starved rats increased their basal level fourfold already at 30 min. These data are presented as evidence that changing nutritional status alters hormonal response to hypovolemic stress.     

Antiphospholipid antibodies and acute-phase response in non-metastatic colorectal cancer patients.

AIM: To investigate the plasma levels and prevalence of the most common antiphospholipid antibodies, as well as their relationships with several plasma markers of inflammation, in order to characterize some aspects of cancer thrombophilia. MATERIALS AND METHODS: Eighty-three cancer patients with non-metastatic colorectal solid tumors and 94 control subjects were tested for the presence of IgG/IgM/IgA anti-cardiolipin and anti-Beta2-glycoprotein I antibodies and of several acute-phase reactants, i.e., fibrinogen, factor VIII:C and C4b-binding protein. RESULTS: In cancer patients the plasma levels of the acute-phase reactants and the IgA/IgG anti-cardiolipin and IgA anti-Beta2- glycoprotein I antibodies were significantly higher; the acute-phase reactants were significantly correlated with anti-cardiolipin antibodies; the prevalence of antiphospholipid antibodies was not significantly higher. CONCLUSIONS: In patients with non-metastatic colorectal cancer the acute-phase response is associated with antiphospholipid generation. This could represent a further pathogenetic mechanism for the short-term post-surgery thrombotic complications of patients with colorectal cancer.     

Local and peripheral cytokine response and CagA status of Helicobacter pylori-positive patients with duodenal ulcer

The mucosal production of TNF-alpha, IL-6, IL-8, IL-10 and nitrotyrosine was investigated in H. pylori-positive patients with duodenal ulcer (DU). The concentrations of these cytokines in gastric antrum mucosal specimens from patients infected with H. pylori (n = 40) were determined by ELISA and compared with data on mucosal specimens from H. pylori-negative patients (n = 12). Nitrotyrosine was determined by ECL Western blotting. It was additionally investigated whether the tissue levels of the cytokines correlated with the peripheral cytokine levels, and the CagA status of the patients. The local TNF-a, IL-6 and IL-8 concentrations in the antral biopsy samples were significantly higher (p < 0.001) in the patients infected with H. pylori than in the samples from the H. pylori-negative subjects. There was a negative correlation between the TNF-alpha and IL-10 concentrations. Further more, in 23 of the 40 biopsy specimens, considerable nitrotyrosine production was detected by ECL Western blotting. There was no significant difference in peripheral TNF-a and IL-6 production between the DU patients and healthy blood donors (n = 100; 58% of whom were also H. pylori-positive). Only the in vitro IL-8-producing capacity was higher in the peripheral blood of the DU group after ex vivo induction with H. pylori. CagA positivity was demonstrated in 39 (97.5%) of the 40 patients with DU, and in 41 (70.7%) of the 58 H. pylori-positive, healthy blood donors. This study suggests that besides the bacterial virulence factor, the host response, with an increased mucosal production of inflammatory cytokines and reactive oxygen and nitrogen species could be relevant to the gastric pathophysiology in H. pylori-induced DU. There is no generalized cytokine overproduction in these DU patients, but the moderate increase in in vitro IL-8 production might be of pathophysiological importance.     

Antioxidant status and proteolytic-antiproteolytic balance in colorectal cancer

Free radicals participate in the development of cancer. When the antioxidant defence system is not longer capable to destroy free radicals they may cause lipid and protein oxidation. Lipid peroxidation products also modify proteins. In such a situation the proteolytic-antiproteolytic balance existing in the blood may be changed. Therefore the aim of this study was to examine the correlation between antioxidant status and activity of proteolytic enzymes and their inhibitors in cases of colorectal cancer. This study included 55 patients with colorectal cancer. The blood was taken before surgery and plasma was collected. Total antioxidant status, the levels of lipid peroxidation products (malondialdehyde and 4-hydroxynonenal) and activity of cathepsin G, elastase and their inhibitors (alpha-1-antitrypsin and alpha-2-macroglobulin) were determined in plasma. It was shown that during the development of cancer total antioxidant status was signficantly decreased while lipid peroxidation products were increased. Activity of alpha-2-macroglobulin was decreased and activity of determined enzymes was not significantly changed. The observed changes indicate a shift in proteolytic-antiproteolytic balance which may enhance carcinogenesis.     

Nutritional status and immune functions in maintenance hemodialysis patients

Epidemiological studies suggest various kinds of immune dysregulation in hemodialysis (HD) patients. The aim of this study was to investigate the relationship between immune functions and nutritional status of HD patients. We studied 54 patients with ESRD on chronic HD, included 34 females and 20 males with mean age 46.6 +/- 16.3 (18-77) years. We measured the height and dry weight of all patients. The BMI was calculated by dividing weight (kg) by height squared (m(2)). In all patients serum urea, creatinine, albumin, iron, cholesterol, triglyceride, CRP, IgG, IgM, IgA, CD4, CD8, CD19, CD16-56 lymphocytes were measured. Kt/V values were calculated according to DOQI guideline. In this study, a positive correlation between albumin, cholesterol, and triglyceride levels as nutritional parameters and immune functions in terms of total and subtype lymphocyte counts was observed. Further prospective studies are needed to determine the clinical importance of this finding and the appropriate means of measurement and effects of nutrition on immune function in hemodialysis patients.     

维持性血液透析患者营养状况的探讨与治疗

由于血液透析技术的广泛开展,慢性肾脏病(chronic kidney disease;CKD)血液透析患者的生活质量得到了明显改善,而血液透析患者的营养不良却仍然是临床医生棘手的问题,并越来越引起人们的重视,它可直接影响血透病人的临床症状、体征、并发症以及存活率等一系列问题.维持性血液透析(Maintenance hemodialysis;MHD)病人发生营养不良时,一般均可出现免疫功能降低,贫血加重,容易感染,心、脑、肺等脏器功能减退,易发生各种严重并发症,导致病人的生活质量下降,长期生存率降低,死亡率增高.营养不良不但影响维持性血液透析患者的生存期和生活质量,同时亦是并发症和死亡率增加的一个重要原因之一,探讨其原因,维持性血液透析病人营养不良的发生,既有血液透析本身的原因,也有血液透析以外的原因,本文从不同角度探讨了MHD患者营养不良的原因、影响因素以及临床上在维持性血液透析(MHD)患者营养不良方面采取的治疗对策.     

The postoperative stress response and its reflection in cytokine network and leptin plasma levels

The objective of the present report was to clarify the postoperative stress response of some inflammatory markers, namely of proinflammatory cytokines and leptin levels during uncomplicated postoperative periods. The results were compared with the dynamics of these parameters during intraabdominal sepsis. We followed 20 patients after a planned resection of colorectal cancer in stage Ib-IV with uncomplicated healing and 13 obese men after laparoscopic non-adjustable gastric banding. These were compared to 12 patients with proven postoperative sepsis. The control group consisted of 18 healthy men. The observed parameters included serum levels of cytokines, tumor necrosis factor-alpha (TNFalpha), interleukin-1 beta (IL-1 beta), interleukin-1 receptor antagonist (IL-1 ra), IL-6, IL-8, soluble receptor of interleukin-2 (sIL-2R) and leptin. It was found that during the first 24 h after resection there was a significant increase in the serum concentration of IL-6 up to 1125+/-240 ng/l, which declined within the next 48-72 h. Serum concentration of TNFalpha was highest 18-24 h after resection (205+/-22 ng/l) and after banding (184+/-77 ng/l). IL-1 beta had a stable serum concentration without significant elevation. Serum concentration of IL-8 after resection rose to 520+/-200 ng/l after 36-48 h. Maximal cytokine levels after gastric banding were quantitatively lower (IL-6 414+/-240 ng/l, TNFalpha 184+/-77 ng/l) than after resection. We found significant elevation of plasma leptin concentration (32+/-10 ng/ml) 24 h after banding compared with preoperative values (18+/-5 ng/ml, p 0.05). Leptin levels 48 and 72 h after banding rapidly returned to the level before operation. During abdominal surgery leptin shows to be an acute phase reactant. Proinflammatory cytokines can be main regulatory factors of leptin during this period. Significant correlation between leptin and TNFalpha (similarly demonstrated by other authors in models of bacterial inflammation) indicates that TNFalpha can be the crucial regulator of leptin generation in the early postoperative period. On the basis of our results we recommend to observe IL-6 and IL-8 at 24-72 h after the surgery in patients with a high risk of early postoperative septic complications.     

口服益生菌对结直肠癌患者术后感染影响的Meta分析

目的 系统评价口服益生菌对结直肠癌患者术后感染的影响.方法 计算机检索PubMed、The Cochrane Library、EMbase、CNKI、WanFang Data和VIP数据库,搜集有关益生菌干预结直肠癌患者术后感染的随机对照试验(randomized controlled trials,RCTs),检索时...     

Energy storage and cytokine response in patients undergoing liver transplantation

Overproduction of pro-inflammatory cytokines during surgery has been known to exert tissue-damaging and lethal effects on the host. Hypermetabolism-associated malnutrition, a common feature of patients with end-stage liver diseases, is related to the presence of a systemic inflammatory response, as reflected by enhanced levels of proinflammatory cytokines. The present study was designed to evaluate energy status of 29 liver transplant recipients, and to assess the relation of energy storage to post-operative cytokine response. The glycogen contents of the graft, and the recipient's abdominal muscle and old liver were measured. The plasma concentrations of tumour necrosis factor alpha, interleukin 1beta, interleukin 6, lactate, pyruvate and total ketone bodies were determined during and after surgery. In undernourished patients, ketone bodies seemed to be the major fuel available to muscle. The concentration of ketone bodies decreased rapidly after the incision, and remained at a low level after reperfusion. These patients had higher plasma levels of lactate/pyruvate ratio and aromatic amino acids during the anhepatic phase, followed by an exaggerated response of cytokines. Depletion of energy storage of the recipients may be involved in the deterioration of peri-operative energy metabolism and the exaggerated post-operative cytokine response.     

益生菌减少结直肠癌术后患者感染的Meta分析

目的 对益生菌改善结直肠癌术后患者的感染与炎性反应的效果进行Meta分析,以得出新的结论。方法 利用PubMed、Embase、CNKI电子期刊数据库、万方数据库和维普数据库,检索益生菌改善结直肠癌术后患者感染和炎性反应的随机对照试验（RCT）文献进行系统评价,应用Review Manager 5.3分析软件进行Meta分析。结果 共检索出17篇相关文献,有10个随机对照研究符合要求,进行两组Meta分析。第一组有9项对照研究共864名受试者（426人为试验组,438人为对照组）纳入分析,Meta分析显示与对照组相比,使用益生菌进行术前肠道准备,可以降低患者术后的感染率（OR=0.34,95%CI：0.23～0.49）,差异有统计学意义（P＜0.01）。另一组有4项对照研究共317名受试者（160人为试验组,157人为对照组）纳入分析,Meta分析显示与对照组相比,使用益生菌进行术前肠道准备,可以减少术后患者的炎性反应（MD=-7.04,95%CI：-9.43～-4.66）,差异有统计学意义（P＜0.01）。结论 益生菌可以降低结直肠癌术后患者的感染与炎性反应。     

Nutritional and pharmacologic support in patients with pancreatic cancer

The aim of our study was to assess whether the influence of nutritional support, consisting of counseling, enteral liquids support and pharmacologic support, can slow down weight loss and whether the change in weight has the impact on the performance status in our patients. In our study 44 patients with pancreatic cancer were included--26 males (mean age 69 years +/- 2.4 years) and 18 females (mean age 63 +/- 3.2 years). Metastatic disease was found in 21 patients, 15 patients had liver metastasis. Locally advanced disease was found in 24 patients and metastatic and locally advanced disease in 17 patients. Surgery was performed in 34 patients. Forty four (100%) patients underwent nutritional counseling, 33 of them (75%) took supplemental enteral feeding and 44 (100%) took megestrol acetate 400 mg per a day. The patients were followed up during 8 weeks during 5 visits. At first visit we took initial nutritional status of patients. Appetite loss, weight gain and Karnofsky performance status were monitored at every visit. All patients were treated with gemcitabin for a 7 week period. Results: NTS score at initial visit in 44 patients (100%) was > or = 5. Using nutritional counseling, enteral food substitution and pharmacological support, weight gain was observed in 61.1% patients and appetite improved. Average KPS mostly improved after first month of therapy while after two months was again at the basal level. With nutritional counseling, supplemental feeding and pharmacologic support weight loss in our patients slowed down and appetite improved. Despite of that, Karnofsky Performance Status didn't change significantly, reflecting the impact of the disease itself and chemotherapy procedures to the patient's condition. We can conclude that nutritional and pharmacological support can temporarily stop weight loss and improve appetite, social life and quality of life in those groups of patients but have no implications on patients KPS and course of their disease.     

Cryptosporidiosis in patients with colorectal cancer

Parasitological examination of feces was carried out for 55 patients with diagnosed colorectal cancer before chemotherapy. Except for Cryptosporidium sp., no other intestinal parasites were found in the specimens; moreover, only the patients with watery diarrhea were Cryptosporidium sp.-positive by enzyme immunoassay. Prevalence of infection in the group of patients with diarrhea (23 persons) was 43.5%, whereas it was 18% for the entire group of patients under study. Coproantigens of this parasite were detected primarily in the patients with tumors located on the left side (in the sigmoid and descending colon).     

The role of molecular markers in predicting response to therapy in patients with colorectal cancer

Advances in systemic therapy for colorectal cancer have dramatically improved prognosis. While disease stage has traditionally been the main determinant of disease course, several molecular characteristics of tumor specimens have recently been shown to have prognostic significance. Although to date no molecular characteristics have emerged as consistent predictors of response to therapy, retrospective studies have investigated the role of a variety of biomarkers, including microsatellite instability, loss of heterozygosity of 18q, type II transforming growth factor beta receptor, thymidylate synthase, epidermal growth factor receptor, and Kirsten-ras (KRAS). This paper reviews the current literature, ongoing prospective studies evaluating the role of these markers, and novel techniques such as gene profiling, which may help to uncover the more complex molecular interactions that will predict response to chemotherapy in patients with colorectal cancer.     

Efficacy of postoperative adjuvant transfusion of cytokine-induced killer cells combined with chemotherapy in patients with colorectal cancer

Purpose

To assess the activity and safety of postoperative adjuvant immunotherapy with transfusion of cytokine-induced killer (CIK) cells combined with chemotherapy in patients with colorectal cancer.

Methods

We retrospectively studied 96 consecutive patients with colorectal cancer who were treated with resection between January 2010 and December 2012 as well as adjuvant chemotherapy. Twenty-one of these patients accepted at least 1 cycle of CIK cell transfusion for immunotherapy (CIK group). Disease free survival (DFS), immune cells and treatment related side effects were assessed. The patients were followed up until May 2013.

Results

By the end of follow-up, 10 patients (10.42 %) had died. Eighteen patients (18.75 %) had withdrawn. All the patients in the CIK group are still alive, and only 1 patient had withdrawn. Patients in the CIK group had significantly longer DFS than those in the control group [HR = 0.28, 95 % CI (0.09, 0.91), p = 0.034]. The 2-year DFS rates of patients in the CIK group and the control group were 59.65 ± 24.80 % and 29.35 ± 6.39 %, respectively. The CD4⁺/CD8⁺ ratios were significantly lower during the period of chemotherapy than those before chemotherapy (p = 0.0038), while the ratios were significantly higher during the period of CIK cell transfusion than those before CIK therapy (p = 0.0484). There were no immediate adverse reactions to the CIK cell transfusions.

Conclusion

Adjuvant transfusion of CIK cells prolongs DFS in patients with colorectal cancer.     

Endotoxin tolerance: regulation of cytokine production and cellular changes in response to endotoxin application in cancer patients.

Endotoxin (lipopolysaccharide, LPS) has the property of inducing tolerance to its own biological effects. This phenomenon has been extensively studied in animal models but only few studies exist on the regulation in humans. Here we describe experiments designed to determine the cytokine regulation and cellular changes in humans during induction of LPS tolerance after repeated LPS injections. Intravenous administration of purified LPS Salmonella abortus equi to cancer patients induces high amounts of circulating tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-8 (IL-8), granulocyte colony-stimulating factor (G-CSF), and macrophage colony-stimulating factor (M-CSF). Repeated injections of LPS at daily intervals resulted in a marked downregulation of the cytokine response and in the case of TNF-alpha, IL-8, G-CSF, and M-CSF the cytokine response was reduced to baseline levels. In contrast, significant increases in serum IL-6 were detected up to day 5 of repeated LPS injections. Hematological changes included transient decreases in WBCs affecting granulocytes, monocytes, and lymphocytes, followed by a marked granulocytosis. The drop in WBCs remained unaltered throughout the 5 day course of repeated LPS injections whereas the granulocyte overshoot recovery diminished gradually. When PBMCs of the cancer patients were restimulated ex vivo a marked enhancement of the capacity to produce TNF-alpha, IL-113, and IL-6 occurred, which is in contrast to the decreasing TNF-alpha serum levels obtained in vivo. In parallel, a shift in monocyte subpopulations from CD14+/CD16- to CD14+/CD16+ cells was observed. The data provide evidence that different mechanisms are implicated in the cytokine downregulation following repeated LPS injections to cancer patients. Furthermore, PBMCs from LPS tolerant patients do not demonstrate a reduction in their capacity to produce cytokines.     

Plasma proinflammatory cytokine response to surgical stress in elderly patients

We investigated the change of plasma cytokines concentrations in elderly patients during lower abdominal surgery. Plasma interleukin (IL-)6 concentrations (68.0+/-15.4 and 36.1+/-20.7 pg/ml) in elderly patients at 24 h and at 3 days after surgery were significantly higher than those (35.1+/-21.5 and 18.6+/-10.6 pg/ml) of young adults. Plasma IL-6 concentrations (92.3+/- 31.9 pg/ml) in elderly patients anesthetized with propofol and fentanyl were significantly higher at the end of the operation than that (57.9+/-36.7 pg/ml) of elderly patients anesthetized with sevoflurane and fentanyl. In conclusion, elderly patients have an increased and delayed IL-6 response to surgical trauma compared with young adults. Plasma IL-6 production after surgical trauma in elderly patients with total intravenous anesthesia with propofol was significantly higher than that in elderly patients with sevoflurane anesthesia.     

Platelet activation in patients with colorectal cancer

Aspirin may reduce the risk of colorectal neoplasia at doses similar to those recommended for the prevention of cardiovascular disease. Thus, we aimed to address whether enhanced platelet activation, as assessed by the measurement of the urinary excretion of 11-dehydro-TXB(2) (a major enzymatic metabolite of TXB(2)), occurs in patients with colorectal cancer. In 10 patients with colorectal cancer, the urinary excretion of 11-dehydro-TXB(2) was significantly higher than in 10 controls, matched for sex, age and cardiovascular risk factors [1001(205-5571) versus 409(113-984) pg/mg creatinine, respectively, median (range), P<0.05]. The administration of aspirin 50 mg daily for 5 consecutive days to colorectal cancer patients caused a cumulative inhibition of platelet cyclooxygenase (COX)-1 activity either ex vivo, as assessed by the measurement of serum TXB(2) levels, or in vivo, as assessed by urinary 11-dehydro-TXB(2) excretion. In conclusion, enhanced platelet activation occurs in colorectal cancer patients. Permanent inactivation of platelet COX-1 by low-dose aspirin might restore anti-tumor reactivity.