Sensitivity value of hematological markers in patients receiving chemoradiotherapy for esophageal squamous cell carcinoma.

BACKGROUND: Hematological markers of the systemic inflammatory response (SIR) including the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and the combination of NLR with PLR (CNP) are associated with prognosis of patients with esophageal squamous cell carcinoma (ESCC). However, their value in predicting the sensitivity to chemoradiotherapy in patients with ESCC is unclear. The aim of this study was to investigate whether these markers can be used as sensitivity predictors for chemoradiotherapy in patients with ESCC. PATIENTS AND METHODS: A total of 114 patients with newly diagnosed ESCC were retrospectively evaluated. They were treated with curative intent by primary radiotherapy only or concurrent chemoradiotherapy. These patients were grouped for further analysis according to the optimum cutoff values of NLR, PLR, and CNP. A univariate analysis was conducted to compare the ability of each of the hematological markers of SIR and clinicopathological characteristics. Multivariate analysis was performed to identify whether the markers were associated with the sensitivity to chemoradiotherapy. The relationship between clinicopathological characteristics and hematological markers was assessed. RESULTS: NLR, CNP, T stage, M stage, and clinical stage were significantly associated with the sensitivity to chemoradiotherapy. In multivariate analysis, CNP and clinical stage were the independent risk factors predicting a poorer sensitivity. CONCLUSION: This study validated novel, easy-to-use hematological markers and found that CNP, an SIR score, is an independent hematological marker of poor sensitivity to chemoradiotherapy in patients with ESCC. This may help guide the planning of follow-up regimens.

Invasive atypical thymic carcinoid: three case reports and literature review.

Atypical thymic carcinoid is an extremely rare thymic neuroendocrine tumor derived from the neuroendocrine system. The aims of this paper were to investigate the clinical features of atypical thymic carcinoid and collate information and experience to improve the diagnosis and treatment of this disease. We describe three cases of atypical carcinoid of the thymus; clinical features, pathological data, treatment modalities, and short-term patient outcomes were summarized and analyzed. The initial clinical symptoms and signs of all three patients were nonspecific and an anterior mediastinal mass was found in each patient on chest computed tomography scan. All three patients underwent surgical resection (total thymectomy and complete excision of the tumor), followed by postoperative radiotherapy, with or without chemotherapy. The diagnoses of three patients were confirmed by pathological and immunohistochemical evaluation. We also present a review of the literature to collate as much information as possible and provide a reference for proper diagnosis and treatment of atypical thyroid carcinoid.

Intratumoral Heterogeneity of Subcutaneous Nodules in a Never-Smoker Woman of Lung Squamous Cell Carcinoma Detected on 18F-Fluorodeoxyglucose Positron Emission Tomography and Computed Tomography: A Case Report.

Subcutaneous tissue is a rare site of metastasis, accounting for only 1-2% of all lung neoplasms. Positron emission tomography (PET) using ¹8F-fluorodeoxyglucose (FDG) has been reported to increase the diagnostic accuracy of subcutaneous metastasis. A 58-year-old woman presented with complaints of dry coughing, in which three positive subcutaneous nodules were found on ¹8F-FDG positron emission tomography and computed tomography (PET/CT). Pathologic examination confirmed that each of the nodules contained 1) necrotic fat, 2) small amounts of blood cells and glandular epithelium, and 3) subcutaneous metastasis of moderately differentiated lung squamous cell carcinoma, respectively. Although PET/CT is useful for the detection of subcutaneous metastasis of primary lung cancer, we noted heterogeneous accumulation of ¹8F-FDG in subcutaneous tumors. This case highlights the importance of obtaining histological confirmation of malignant diseases whenever possible.

Spect-guidance to reduce radioactive dose to functioning lung for stage III non-small cell lung cancer.

OBJECTIVE: To investigate the treatment effect of additional information obtained by single photon emission computed tomography (SPECT) lung perfusion imaging (LPI) in the radiotherapy planning process for patients with stage III non-small cell lung cancer (NSCLC). METHODS: 39 patients with stage III NSCLC were enrolled. Gross tumor volume (GTV) was outlined by SPECT/CT images, SPECT-LPIs being used to define functional lung (FL) and non-functional lung (NFL) regions. Two sets of IMRT plans were designed to deliver 64Gy to PTV. One was a regular IMRT plan using CT images only (Plan 1), and the other was a corresponding IMRT plan using co-registered images (Plan 2). FLVx (the % volume of functional lung receiving ≥x Gy) and WLVx (% volume of whole lung to receive ≥x Gy) were compared by paired Student's t test. Kendalls correlation was used to analyze the factor (s) related with the FLV20 decrease. RESULTS: Compared with plan 1, both WLVx and FLVx were decreased in plan 2. WLV10, WLV15, WLV20, WLV25, WLV30 and WLV35 decreased 9.7%, 13.8%, 17.2%, 12.9%, 9.8% and 9.8%, and FLV10, FLV15, FLV20, FLV25, FLV30 and FLV35 decreased 10.8%, 14.6%, 17.3%, 14.5%, 14.5% and 10.5%. FLVx decreased significantly compared with WLVx. There were significant differences in WLV10, WLV15, WLV20, WLV25, WLV3 and FLV10, FLV15, FLV20, FLV25, FLV30 between plan 1 and plan 2 (P=0.002, 0.000, 0.000, 0.005, 0.027 and 0.002, 0.000, 0.000, 0.006, 0.010). According to Kendall correlation analysis, NFL had a negative relation with the percentage FLV20 decrease (r=-0.559, P<0.01), while the distance of PTV and NFL center had a significantly positive relation with the percentage of FLV20 decrease (r=0.768, P<0.01). CONCLUSION: Routine use of SPECT-LPI for patients undergoing radiotherapy planning for stage III NSCLC appears warranted.

Feasibility of shrinking field radiation therapy through 18F-FDG PET/CT after 40 Gy for stage III non-small cell lung cancers.

OBJECTIVE: To explore the feasibility of shrinking field technique after 40 Gy radiation through 18F-FDG PET/ CT during treatment for patients with stage III non-small cell lung cancer (NSCLC). METHODS: In 66 consecutive patients with local-advanced NSCLC, 18F-FDG PET/CT scanning was performed prior to treatment and repeated after 40 Gy. Conventionally fractionated IMRT or CRT plans to a median total dose of 66 Gy (range, 60-78 Gy) were generated. The target volumes were delineated in composite images of CT and PET. Plan 1 was designed for 40 Gy to the initial planning target volume (PTV) with a subsequent 20-28 Gy-boost to the shrunken PTV. Plan 2 was delivering the same dose to the initial PTV without shrinking field. Accumulated doses of normal tissues were calculated using deformable image registration during the treatment course. RESULTS: The median GTV and PTV reduction were 35% and 30% after 40 Gy treatment. Target volume reduction was correlated with chemotherapy and sex. In plan 2, delivering the same dose to the initial PTV could have only been achieved in 10 (15.2%) patients. Significant differences (p<0.05) were observed regarding doses to the lung, spinal cord, esophagus and heart. CONCLUSIONS: Radiotherapy adaptive to tumor shrinkage determined by repeated 18F-FDG PET/CT after 40 Gy during treatment course might be feasible to spare more normal tissues, and has the potential to allow dose escalation and increased local control.

Phase I study of pemetrexed, cisplatin, and concurrent radiotherapy in patients with locally advanced non-small cell lung cancer.

OBJECTIVES: Concurrent chemoradiotherapy in well-selected locally advanced non-small cell lung cancer (LANSCLC) is considered as standard therapy. However, the choice of anticancer agents is still unresolved. Our objectives were to determine the maximum tolerated dose and recommended dose of pemetrexed in combination with cisplatin, with concurrent late course accelerated hyperfractionated (LCAF) intensity modulated radiotherapy (IMRT) in patients with LANSCLC and to investigate the safety and efficacy. METHODS: The chemotherapy was cisplatin (25 mg/m(2) × 3 days) plus pemetrexed with doses escalating from 400 to 500 mg/m(2). The dose level was increased every 3 patients. The gross tumor volumes of concurrent LCAF IMRT were delineated according to [(18)F] fluorodeoxyglucose positron emission tomography computed tomography imaging. To spare functional lung, single photon emission photography lung perfusion imaging was used to optimize the plans. The total radiation dose was limited such that the V20 of bilateral lung is no more than 35%. RESULTS: Nine patients with LANSCLC were enrolled in this study. The median radiation dose was 70.8 Gy. The response rate was 66.7% with a complete remission rate of 33.3%. Toxicity was mild with only 1 patient experiencing dose limiting toxicity in 500 mg/m(2) level. Obviously, the maximum tolerated dose was not reached as per the definition. As the systemically active chemotherapy dose was reached, further dose escalation was discontinued, and the recommended dose of pemetrexed for a phase II study was 500 mg/m(2). CONCLUSIONS: The combination of pemetrexed and cisplatin with concurrent LCAF IMRT optimized based on single photon emission photography lung perfusion imaging is well tolerated in patients with LANSCLC. Full therapeutic doses of the chemotherapy can be safely administered. The initial results showed signs of efficacy.

Clinical and dosimetric risk factors of acute esophagitis in patients treated with 3-dimensional conformal radiotherapy for non-small-cell lung cancer.

PURPOSE: To analyze the clinical and dosimetric risk factors of acute esophagitis (AE) in non-small-cell lung cancer (NSCLC) patients treated with 3-dimensional conformal radiotherapy (3D-CRT). METHODS AND MATERIALS: One hundred two NSCLC patients treated with 3D-CRT were retrospectively analyzed. Forty of these 102 patients analyzed were treated with concurrent chemotherapy (CCT). The median biologic effective dose of radiotherapy was 72.0 Gy. AE was scored according to the Radiation Therapy Oncology Group criteria. The clinical and dosimetric factors associated with grade 2 or worse AE were analyzed using univariate and multivariate binary logistic analysis. RESULTS: There were no grade 4 or 5 AE observed in the 102 patients analyzed. Thirty-four of 102 patients (33.3%) developed grade 2 or 3 AE. Univariate analysis showed that clinical factors, such as lymph nodes stage (N 0/1 vs. N 2/3), pretreatment weight loss > or =5%, CCT, and the use of late-course hyperfractionated radiotherapy were significantly associated with grade 2 and 3 AE. Dose volume parameters of esophagus including mean esophageal dose, maximal esophageal dose, rV15, rV20, rV25, rV30, rV35, rV40, rV45, rV50, rV55, rV60 were also associated with AE. On multivariate forward step-wise logistic analysis, CCT, lymph nodes stage, and rV55 emerged as the statistically most significant factors of AE with OR parameters of 8.911, 4.832, and 1.083, respectively. CONCLUSION: CCT, lymphatic status, and rV55 were strong predictors of grade 2 or worse AE in NSCLC treated with 3D-CRT.

Phase I study of concurrent selective lymph node late course accelerated hyper-fractionated radiotherapy and Capecitabine, Cisplatin for locally advanced esophageal squamous cell carcinoma.

Twelve patients with locally advanced esophageal squamous cell carcinoma were enrolled to evaluate the safety and efficacy of concurrent chemo-radiotherapy. Dose-limiting toxicity was mainly observed at Capecitabine 1500 mg. The maximum-tolerated dose/recommended dose of Capecitabine was 1000 mg. The Kaplan-Meier estimated overall l-year survival rate was 100%.

[Effect of high mobility group B1 protein on the function of phagocytosis and the expression of I-A/-E of peritoneal macrophages in mice].

AIM: To investigate the effect of extracellular high mobility group B1 protein (HMGB1) on the immunological function of macrophages. METHODS: Peritoneal macrophages from mice were stimulated by concentration gradient HMGB1 in vitro. Male BALB/c mice were divided randomly into control group (normal saline, i.p.), low or high dose group (treated with HMGB1 0.2 microg or 20 microg per mouse, respectively, i.p.). Phagocytosis of neutral red and I-A/-E expression of macrophages was assayed. RESULTS: (1) HMGB1 regulated the phagocytosis of macrophages in a time- and dose-dependent manner, but it did not regulate the expression of I-A/-E in vitro. Moreover, the phagocytosis of macrophages was significantly enhanced by stimulating of HMGB1 at a concentration of 10 microg/L as compared with other stimulating concentrations at culture-hour 6 and 12 (P<0.05 or P<0.01). (2) The capacity for phagocytosis of macrophages was reduced from 43% to 67% when the mice were challenged with HMGB1 in vivo. However, as compared with animals in control group, neutral red phagocytosis of macrophages was depressed markedly in the animals inflicted with high dose HMGB1 for 24 hours (P<0.05). The I-A/-E expression of macrophages was up-regulated markedly in the animals inflicted with low dose HMGB1 for 48 hours as compared to animals treated with normal saline and high dose HMGB1(P<0.05 or P<0.01). CONCLUSION: High dose HMGB1 can depress the phagocytosis of macrophages, and low dose HMGB1 can enhance macrophage-mediated immunity. Moderate HMGB1 loading is beneficial to immune defense.

[A new model of skin avulsion injuries in rats].

OBJECTIVE: To create a stable and reliable model of skin avulsion in rats. METHODS: 30 male, SD rats were randomly divided into axial pattern skin flap (9 cm x 3 cm) group and random pattern skin flap group (6 cm x 4 cm), each having the control groups and avulsion groups. Flaps were subjected to avulsion force of 6 kg in axial pattern skin flaps or 8 kg in random pattern skin flaps, and the lasting time was 8 s or 12 s, respectively. Retraction of wounds and necrosis of skin flaps were observed. RESULTS: There was more significant wound retraction in avulsion groups than that in control groups on post-operation day 7 (P < 0.05). The proportion of the wound retraction increased by 1 fold in avulsion groups on post-operation day 14 as compared to post-operation day 7 (P < 0.01). Interestingly, necrosis of partial or most of skin flaps was observed in all animals of avulsion groups, while slight necrosis happened in one of six in control animals. The necrosis area of flaps was 38% - 77% when avulsed for 8 s, and was 40% - 80% when avulsed for 12 s in axial pattern skin flaps. However, the necrosis area in random pattern skin flaps was smaller than that in axial pattern skin flaps, from 17% - 40% when avulsed for 8 s to 24% - 43% when avulsed for 12 s. CONCLUSIONS: It might be possible to create animal model of skin avulsion injuries with rats.

[Effect of high mobility group box 1 protein on proliferation and apoptosis and balance between Th1/Th2 and Tc1/Tc2 of lymphocytes in vitro].

AIM: To explore whether extracellular high mobility group B1 protein (HMGB1) plays a role in regulation of lymphocyte-mediated immune. METHODS: Lymphocytes originated from mice spleens were stimulated with concentration gradient HMGB1 or combined with ConA in vitro. Then, the proliferation of lymphocytes was assayed with MTT, quantitative and qualitative analysis of apoptosis in lymphocytes and expression of CD3 and CD8 on cells surface and IL-4 and IFN-gamma within cells were assessed using flow cytometry. Levels of interleukin-2 (IL-2) and soluble IL-2R (sIL-2R) of culture supernatant were assayed by ELISA. RESULTS: (1) HMGB1 regulated the proliferation of lymphocytes in a time- and dose-dependent manner, but did not influence the apoptosis of lymphocytes. (2) The ratio of Th to Tc increased from 2.6:1 at culture-hour 0 to 5-7:1 at culture-hour 12 and 24, but that did not change with the stimulation of HMGB1. There were no significant difference in the population and percentage of Th1 and Th2, as well as Tc1 and Tc2, when stimulated with HMGB1. However, HMGB1 in concentrations of 10 and 100 microg/L favored Th1 differentiation, and 1 and 10 microg/L HMGB1 favored Tc1 differentiation. (3) Levels of IL-2 were increased, and sIL-2R decreased, significantly, when stimulated with 10 microg/L HMGB1 for 12 h, thus the ratio of IL-2 to sIL-2R was markedly higher, as compared with 0 and 1000 microg/L HMGB1 (P<0.05 or P<0.01). CONCLUSION: Low dose HMGB1 could be in favor of the bias of Th1 and Tc1, and improve the lymphocyte-mediated immune.

[Effects of escharectomy during shock stage on tissue high mobility group box-1 expression and balance of pro-/anti-inflammatory response in rats after severe thermal injury].

OBJECTIVE: To investigate the effects of escharectomy during shock stage on tissue high mobility group box-1 protein (HMGB1) expression and balance of pro-/anti-inflammatory cytokines, and to elucidate the potential mechanism underlying beneficial effect of early escharectomy after severe burns. METHODS: Wistar rats inflicted by 30% full-thickness thermal injury were randomly divided into thermal injury group, 24 h escharectomy group and 72 h escharectomy group, in which escharectomy were performed at 24 and 72 h postburn, respectively. Gene expression of HMGB1, interleukin-10 (IL-10), and tumor necrosis factor-alpha (TNF-alpha) in liver and lungs was detected with reverse-transcription PCR, and protein levels of IL-10 and TNF-alpha in liver and lung tissues were measured by ELISA. The plasma AST and ALT contents, and pulmonary myeloperoxidase (MPO) activity were also assayed. RESULTS: The mRNA expression of HMGB1 and TNF-alpha in liver and lungs was up-regulated on postburn day 2, with IL-10 over-expression on postburn day 8. In the 24 h escharectomy group, HMGB1 and TNF-alpha mRNA expression in liver and lungs was down-regulated on postburn day 4, and IL-10 expression returned to normal range on postburn day 8, while the down-regulation of HMGB1, TNF-alpha and IL-10 were not noted in the 72 h escharectomy group. There were two peaks in liver TNF-alpha protein levels appearing on postburn days 2 and 8, respectively, with an unexpected marked decrease on day 4 in thermal injury controls, yet liver TNF-alpha levels maintained in normal range in animals of 24 h and 72 h escharectomy groups. The ratios of TNF-alpha to IL-10 protein levels in liver tissue were significantly increased on postburn days 2 and 4 (P = 0.0001 and 0.002, respectively), while escharectomy during shock stage markedly reduced hepatic TNF-alpha to IL-10 ratios (P = 0.0008 and 0.040, respectively). No significant changes in TNF-alpha protein levels in lung tissue were observed. Additionally, plasma AST as well as ALT contents, and pulmonary MPO activity were markedly decreased on postburn days 4 and 8 in the 24 h escharectomy group compared to the 72 h escharectomy group or thermal injury controls (P < 0.05). CONCLUSIONS: Escharectomy during burn shock stage could inhibit the over-expression of both early and late inflammatory mediators, and maintain the balance of pro-/anti-inflammatory response, thereby improving multiple organ functions in rats following severe burns.

[The protective effect of supplementation of probiotics combined with riboflavin on the intestinal barrier of the rats after scald injury].

OBJECTIVE: To investigate the effect and its possible mechanism of the supplementation of probiotics combined with riboflavin on the intestinal barriers of the rats after scald injury. METHODS: Seventy Wistar rats were used in the study and were randomly divided into scald control (SC, n = 30), scald and treatment (ST, n = 30) and normal control (NC, n = 10) groups. The rats in SC and ST groups were subjected to 30% TBSA III degree scald. 1.5 ml of isotonic saline suspension containing 5 x 10(12) CFU/L of Bifidobacteria, 5 x 10(10) CFU/L of Bacillus cereus and 5 mg/L of riboflavin was given to rats by gavage in ST group twice a day. For the rats in SC and NC group equal amount of isotonic saline was fed twice a day. The changes in the incidence of bacterial translocation, the amount of intestinal membranous flora, the synthesis and secretion of SIgA in the ileum, and the repair of injured intestinal mucosa were observed. RESULTS: The incidence of bacterial translocation in ST group was significantly lower than that in SC group (P = 0.000 - 0.025). The plasma level of endotoxin in ST group was markedly lower than that in SC group on 3 post-scald day (PSD) (P < 0.05). The amount of bifidobacteria in caecal membrane flora increased by about 20 to 40 fold, whereas the amounts of E. coli and fungi significantly decreased (P < 0.01). The membranous injury scoring was 3 to 0 on 5 PSD (P < 0.05), and the SIgA content in intestinal mucus returned to normal value on the 5th PSD (P < 0.01) in the ST group. CONCLUSION: Supplementation of probiotics together with riboflavin could ameliorate translocation of bacteria and endotoxin in rats with scald injury, implying that the intestinal barrier function was effectively protected.

Risk factors of development of gut-derived bacterial translocation in thermally injured rats.

AIM: Studies have demonstrated that gut-derived bacterial translocation (BT) might play a role in the occurrence of sepsis and multiple organ dysfunction syndrome (MODS). Yet, no convincing overall analysis of risk factors for BT has been reported. The purpose of this study was to evaluate the related factors for the development of BT in burned rats. METHODS: Wistar rats were subjected to 30% third-degree burns. Then samples were taken on postburn d 1, 3, and 5. Incidence of BT and counts of mucosal bifidobacteria, fungi and E. coli, mucus sIgA, degree of injury to ileal mucosa, and plasma interleukin-6 were observed. Univariate analysis and multivariate logistic regression analysis were performed. RESULTS: The overall BT rate was 53.9% (69 in 128). The result of univariate analysis showed that the levels of plasma endotoxin and interleukin-6, the counts of mucosal fungi and E. coli, and the scores of ileum lesion were markedly increased in animals with BT compared with those without (P=0.000-0.005), while the levels of mucus sIgA and the counts of mucosal bifidobacteria were significantly reduced in animals with translocation compared with those without (P=0.000). There was a significant positive correlation between mucus sIgA and the counts of mucosal bifidobacteria (r=0.74, P=0.001). Moreover, there were strong negative correlations between scores of ileum-lesion and counts of bifidobacteria (r=-0.67, P=0.001). Multivariate logistic regression revealed that ileum lesion score (odds ratio [OR] 45.52, 95% confidence interval [CI] 5.25-394.80), and counts of mucosal bifidobacteria (OR 0.039, 95% CI 0.0032-0.48) were independent predictors of BT secondary to severe burns. CONCLUSION: Ileal lesion score and counts of mucosal bifidobacteria can be chosen as independent prognosis factors of the development of BT. Specific interventions targeting these high-risk factors might be implemented to attenuate BT, including strategies for repair of damaged intestinal mucosae and restoration of the balance of gastrointestinal flora.

[Influence of escharectomy during shock stage on the systemic and intestinal immune function in scalded rats].

OBJECTIVE: To investigate the influence of escharectomy during shock stage on systemic and intestinal immune function and its mechanism in scalded rats. METHODS: Ninety-six Wistar rats were employed in the study of which 8 were used as normal control group. The donor skin from the trunk in twenty-four rats were preserved in liquid nitrogen. The other 64 rats were subjected to 30% full-thickness scalding, and they were randomly divided into A (n = 24, no treatment after scalding), B (n = 24) and C (n = 16) groups. Physiological saline was intraperitoneally injected (50 ml/kg) on the 24 post-scalding hours to the rats in the B and C groups. The rats in B group underwent escharectomy during shock stage, and the excision wounds were covered with the cryo-preserved alloskin. The rats in C group received the same treatment as in B group but at 72 post-scalding hours. The change in the proliferative ability of splenic lymphocytes, the plasma and intestinal tissue content of interleukin 2 (IL-2), the contents of sIgA in intestinal mucus, and the content of DAO in the intestinal tissue were observed on 2, 4 and 8 post burn days (PBD) in A and B groups and also on 4 and 8 PBD in C group, respectively. RESULTS: The splenocytic proliferative ability, IL-2 level in the plasma and intestinal tissue, and the sIgA content in intestinal mucus in the rats in A, B and C groups were lower than that in control group at all time points (P < 0.05). The proliferative ability of splenic lymphocytes in B group on 4 and 8 PBD and in C group on 8 PBD respectively was similar to that in control group. Whereas the IL-2 content in plasma and in intestinal tissue was higher in B and C groups than that in A group (P < 0.01). The sIgA content in intestinal mucus in B group was twice of that in C group respectively [(3.51 +/- 2.14) mg/g vs (1.40 +/- 0.64) mg/g, (3.03 +/- 0.95) mg/g vs (1.52 +/- 1.26) mg/g (P < 0.05 or P < 0.01)] on 4 and 8 PBD. The DAO activity in the intestinal tissue in A group was lower than that in control and B group (P < 0.05) on 4 and 8 PBD. CONCLUSION: Escharectomy during shock stage might be beneficial to the recovery of the systemic and intestinal immune functions in rats with scalding injury.

[Bifidobacterial supplement enhances the expression and excretion of intestinal sIgA in severely burned rats].

OBJECTIVE: To investigate the potential effect of bifidobacterial supplement on intestinal mucosal immunity associated with severe burns. METHODS: Wistar rats were randomly divided into burn control group (BC group, n = 30), treatment group (BT group, n = 30), and sham-burn group (NC group, n = 10). Rats in BT group were fed bifidobacterial preparation (5 x 10(9) CFU/ml) after 30% total body surface area full-thickness burns, 1.5 ml, twice daily. Rats in BC group and NC group were fed normal saline, 1.5 ml, twice daily. Samples were taken on post-burn 1-, 3-, and 5-day. The incidence of bacterial translocation and bifidobacteria counts in the cecum mucosa were determined with standard methods. The sIgA levels in the mucus of the small intestine were measured by RIA. The positive sIgA expression in the lamina propria was detected by immunohistochemical staining. RESULTS: The incidence of bacterial translocation was 42% and 16% in BC and BT groups on post-burn day 3 (P = 0.004), 30% and 8% on day 5 (P = 0.002), respectively. Plasma endotoxin levels were markedly higher in BC and BT groups than in NC group at the early stage post-burn. There was a significant decrease between BT group and BC group on post-burn day 1 (P = 0.0412). Bifidobacteria counts in cecum mucosa were reduced by 10- to 60-fold after thermal injury, but there was a remarkable increase in bifidobacteria counts in animals fed with bifidobacteria. sIgA levels in the intestinal mucus were significantly decreased in group BC, but they returned to normal range in BT group on post-burn day 5. Similarly, sIgA expression in the lamina propria was also weakened after burns, and had a tendency to recover after prescription of a 5-day bifidobacteria-supplemented formula. A strong positive correlation was observed between the counts of bifidobacteria in the cecal mucosa and the levels of sIgA in the intestinal mucus (r = 0.7534, P = 0.0000). CONCLUSIONS: The expression and excretion of sIgA in the intestine appear to be markedly inhibited following a severe thermal injury. The supplement of exogenous bifidobacteria could improve sIgA formation in the small intestine, thereby reducing the incidence of bacterial/endotoxin translocation secondary to major burns.

[Improvement of bifidobacterial supplement on the barrier function of intestinal mucosa and microbe flora induced by thermal injury in rats].

OBJECTIVE: To investigate the potential effect of bifidobacterial supplement on intestinal mucosal and biological barrier following severe burns. METHODS: Seventy Wistar rats were randomly divided into burn control group (BC, n=30), burn + treatment group (BT, n=30), and sham-burn group (NC, n=10). Animals in BT group were fed bifidobacterial preparation (5x10(12) CFU/L) after 30% total body surface area (TBSA) full-thickness thermal injury, 1.5 ml, twice daily. Samples were taken on postburn days 1,3,and 5. The incidence of bacteria/endotoxin translocation and the counts of bifidobacteria, E.coli, and fungi in ileo-cecum mucosa were determined with standard methods. Ileum mucosal injuries were evaluated light and electron microscopically by blinded examiners. RESULTS: (1) The incidence of bacterial translocation were 42% and 16% in BC and BT groups on postburn day 3 (P=0.004 0), 30% and 6% on day 5 (P=0.002 0), respectively. Plasma endotoxin levels were markedly higher in BC and BT groups than that in NC group at the early stage postburn, while there was a significant decrease in BT group compared with BC group on postburn day 1 (P=0.04). (2) The bifidobacteria counts in ileo-cecum mucosa were reduced by 10- to 60-fold after thermal injury, while there was a remarkable increase in animals fed with bifidobacteria. The E.coli counts in ileo -cecum mucosa were increased by 20- to 30-fold on postburn days 1 and 3, whereas those markedly reduced after 3-day bifidobacteria-supplemented formula, tending to normal range.(3)There were obviously ileum mucosal lesions on postburn days 1 and 3,the ileum lesion scores remained significant higher in B C group than that in NC group on postburn 5 day (P<0.05).However,the damage d ileum mucosa was markedly repaired after 3-day bifidobacteria-supplemented formula, and almost restored 5 days later. CONCLUSION: The intestinal mucosal and biological barrier appear to be markedly damaged after severe burns. The supplement of exogenous bifidobacteria can facilitate the improvement of mucosal as well as biological barrier function, thereby reducing the incidence of bacteria/endotoxin translocation secondary to major burns.