ABSTRACT
BACKGROUND: Fluid overload (FO) after resuscitation is frequent and contributes to adverse outcomes among postinjury open abdomen (OA) patients. Bioelectrical impedance analysis (BIA) is a promising tool for monitoring fluid status and FO. Therefore, we sought to investigate the efficacy of BIA-directed fluid resuscitation among OA patients. METHODS: A pragmatic, prospective, randomized, observer-blind, single-center trial was performed for all trauma patients requiring OA between January 2013 and December 2017 to a national referral center. A total of 140 postinjury OA patients were randomly assigned in a 1:1 ratio to receive either a BIA-directed fluid resuscitation (BIA) protocol that included fluid administration with monitoring of hemodynamic parameters and different degrees of interventions to achieve a negative fluid balance targeting the hydration level (HL) measured by BIA or a traditional fluid resuscitation (TRD) in which clinicians determined the fluid resuscitation regimen according to traditional parameters during 30 days of ICU management. The primary outcome was the 30-day primary fascial closure (PFC) rate. The secondary outcomes included the time to PFC, postoperative 7-day cumulative fluid balance (CFB) and adverse events within 30 days after OA. The Kaplan-Meier method and the log-rank test were utilized for PFC after OA. A generalized linear regression model for the time to PFC and CFB was built. RESULTS: A total of 134 patients completed the trial (BIA, n = 66; TRD, n = 68). The BIA patients were significantly more likely to achieve PFC than the TRD patients (83.33% vs. 55.88%, P < 0.001). In the BIA group, the time to PFC occurred earlier than that of the TRD group by an average of 3.66 days (P < 0.001). Additionally, the BIA group showed a lower postoperative 7-day CFB by an average of 6632.80 ml (P < 0.001) and fewer complications. CONCLUSION: Among postinjury OA patients in the ICU, the use of BIA-guided fluid resuscitation resulted in a higher PFC rate and fewer severe complications than the traditional fluid resuscitation strategy.
Subject(s)
Electric Impedance/therapeutic use , Fascia/drug effects , Fluid Therapy/instrumentation , Open Abdomen Techniques/instrumentation , Adult , Analysis of Variance , Fascia/physiopathology , Female , Fluid Therapy/methods , Fluid Therapy/standards , Humans , Male , Middle Aged , Open Abdomen Techniques/methods , Open Abdomen Techniques/standards , Prospective Studies , Water-Electrolyte Balance/physiology , Wounds and Injuries/therapyABSTRACT
The management of enterocutaneous fistulas (ECF) can be challenging because of massive fluid loss, which can lead to electrolyte imbalance, severe dehydration, malnutrition and sepsis. Nutritional support plays a key role in the management and successful closure of ECF. The principle of nutritional support for patients with ECF should be giving enteral nutrition (EN) priority, supplemented by parenteral nutrition if necessary. Although total parenteral nutrition (TPN) may be indicated, use of enteral feeding should be advocated as early as possible if patients are tolerant to it, which can protect gut mucosal barrier and prevent bacterial translocation. A variety of methods of enteral nutrition have been developed such as fistuloclysis and relay perfusion. ECF can also be occluded by special devices and then EN can be implemented, including fibrin glue application, Over-The-Scope Clip placement and three-dimensional (3D)-printed patient-personalized fistula stent implantation. However, those above should not be conducted in acute fistulas, because tissues are edematous and perforation could easily occur.
ABSTRACT
BACKGROUND: The etiology of hypertriglyceridemia (HTG) and, consequently, HTG-induced acute pancreatitis (HTG-AP), is complex. OBJECTIVE: Herein, we explore a possible gene-environment interaction between APOA5 c.553G>T (p.185Gly>Cys, rs2075291), a common variant associated with altered triglyceride levels, and pregnancy in HTG-AP. METHODS: We enrolled 318 Chinese HTG-AP patients and divided them into 3 distinct groups: Group 1, male patients (n = 183); Group 2, female patients whose disease was unrelated to pregnancy (n = 105); and Group 3, female patients whose disease was related to pregnancy (n = 30). APOA5 rs2075291 genotype status was determined by Sanger sequencing. A total of 362 healthy Han Chinese subjects were used as controls. Data on body mass index, peak triglyceride level, age of disease onset, episode number, and clinical severity of HTG-AP were collected from each patient. Multiple comparisons, between patient groups, between patient groups and controls, or within each patient group, were performed. RESULTS: A robust association of APOA5 rs2075291 with HTG-AP in general, and HTG-AP during pregnancy in particular, was demonstrated. The minor T allele showed a stronger association with Group 3 patients than with either Group 1 or Group 2 patients. This stronger association was due mainly to the much higher frequency of TT genotype in Group 3 patients (20%) than that (<6%) in Group 1 and Group 2 patients. Moreover, the TT genotype was associated with a significantly higher peak triglyceride level in Group 3 patients compared with the GG genotype. CONCLUSION: Our findings provide evidence for an interaction between APOA5 rs2075291 and pregnancy in HTG-AP.
Subject(s)
Apolipoprotein A-V/genetics , Gene-Environment Interaction , Hypertriglyceridemia/complications , Pancreatitis/etiology , Pancreatitis/genetics , Polymorphism, Single Nucleotide , Pregnancy Complications/genetics , Adult , Alleles , Female , Gene Frequency , Genotype , Humans , Middle Aged , Pregnancy , Young AdultABSTRACT
BACKGROUND: Hypertriglyceridemia (HTG) is a leading cause of acute pancreatitis. HTG can be caused by either primary (genetic) or secondary etiological factors, and there is increasing appreciation of the interplay between the two kinds of factors in causing severe HTG. OBJECTIVES: The main aim of this study was to identify the genetic basis of hypertriglyceridemia-induced acute pancreatitis (HTG-AP) in a Chinese family with three affected members (the proband, his mother and older sister). METHODS: The entire coding and flanking sequences of LPL, APOC2, APOA5, GPIHBP1 and LMF1 genes were analyzed by Sanger sequencing. The newly identified LPL nonsense variant was subjected to functional analysis by means of transfection into HEK-293 T cells followed by Western blot and activity assays. Previously reported pathogenic LPL nonsense variants were collated and compared with respect to genotype and phenotype relationship. RESULTS: We identified a novel nonsense variant, p.Gln118* (c.351C > T), in the LPL gene, which co-segregated with HTG-AP in the Chinese family. We provided in vitro evidence that this variant resulted in a complete functional loss of the affected LPL allele. We highlighted a role of alcohol abuse in modifying the clinical expression of the disease in the proband. Additionally, our survey of 12 previously reported pathogenic LPL nonsense variants (in 20 carriers) revealed that neither serum triglyceride levels nor occurrence of HTG-AP was distinguishable among the three carrier groups, namely, simple homozygotes, compound heterozygotes and simple heterozygotes. CONCLUSIONS: Our findings, taken together, generated new insights into the complex etiology and expression of HTG-AP.
Subject(s)
Codon, Nonsense/genetics , Hypertriglyceridemia/complications , Lipoprotein Lipase/genetics , Pancreatitis/etiology , Pancreatitis/genetics , Adult , Heparin/pharmacology , Heterozygote , Humans , Hypertriglyceridemia/blood , Male , Pancreatitis/blood , Pancreatitis/diagnostic imaging , Triglycerides/bloodABSTRACT
BACKGROUND: Most studies on enhanced recovery after surgery (ERAS) for gastric cancer exclude patients who received neoadjuvant chemotherapy. Here, we aimed to evaluate whether patients who received neoadjuvant chemotherapy can be enrolled into the ERAS program for locally advanced gastric cancer. METHODS: From April 2015 to July 2017, 114 patients who received neoadjuvant chemotherapy for locally advanced gastric cancer were randomized into ERAS and standard care (SC) groups. Postoperative length of stay, complications, bowel function, and nutritional status were recorded. RESULTS:: The postoperative length of stay of the ERAS group was shorter compared with that of the SC group (5.9 ± 5.6 vs. 8.1 ± 5.3 days, P = 0.037). The postoperative complication rate was 9.3% in the ERAS group and 11.5% in the SC group (P = 0.700). The time to first flatus (2.7 ± 2.0 vs. 4.5 ± 4.6 days, P = 0.010) and time to a semi-liquid diet (3.2 ± 2.1 vs. 6.3 ± 4.9 days, P < 0.001) in the ERAS group were shorter compared with those in the SC group. On the 10th day after surgery, the values of weight, total protein, albumin, and prealbumin of the ERAS group were lower compared with those of the SC group. CONCLUSIONS:: Patients who received neoadjuvant chemotherapy could be enrolled into ERAS programs for locally advanced gastric cancer. The nutritional status of these patients was not adversely affected.
Subject(s)
Stomach Neoplasms/surgery , Aged , Female , Gastrectomy , Humans , Length of Stay , Male , Middle Aged , Neoadjuvant Therapy , Nutritional Status , Stomach Neoplasms/drug therapyABSTRACT
BACKGROUND: Intestinal fistula is one of the common complications of Crohn's disease (CD) that might require surgical treatment. The clinical characteristics and outcomes of CD with intestinal fistula are much different from CD alone. This study was to investigate whether the coagulation status of CD is changed by intestinal fistula. METHODS: Data were retrospectively analyzed for 190 patients with a definitive diagnosis of CD who were registered at the Jinling Hospital between January 2014 and September 2015. Baseline clinical characteristics and laboratory indices of initial admission and 7 days after intestinal fistula resections were collected. Student's t-test and the Wilcoxon rank-sum test were used to compare differences between the two groups. RESULTS: Compared with CD patients without intestinal fistula, prothrombin time (PT) in patients with intestinal fistula was significantly longer (12.13 ± 1.27 s vs. 13.18 ± 1.51 s, P < 0.001 in overall cohort; 11.56 ± 1.21 s vs. 12.61 ± 0.73 s, P = 0.001 in females; and 12.51 ± 1.17 s vs. 13.37 ± 1.66 s, P = 0.003 in males). Platelet (PLT) count was much lower in intestinal fistula group than in nonintestinal fistula group (262.53 ± 94.36 × 109/L vs. 310.36 ± 131.91 × 109/L, P = 0.009). Multivariate logistic regression showed that intestinal fistula was significantly associated with a prolonged PT (odds ratio [OR] = 1.900, P < 0.001), a reduced amount of PLT (OR = 0.996, P = 0.024), and an increased operation history (OR = 5.408, P < 0.001). Among 65 CD patients receiving intestinal fistula resections, PT was obviously shorter after operation than baseline (12.28 ± 1.16 s vs. 13.02 ± 1.64 s, P = 0.006). CONCLUSIONS: Intestinal fistula was significantly associated with impaired coagulation status in patients complicated with CD. Coagulation status could be improved after intestinal fistula resections.
Subject(s)
Blood Coagulation/physiology , Crohn Disease/physiopathology , Inflammatory Bowel Diseases/physiopathology , Intestinal Fistula/physiopathology , Adult , Female , Humans , Male , Middle Aged , Odds Ratio , Prothrombin Time , Retrospective Studies , Young AdultABSTRACT
INTRODUCTION: Increased circulating endothelial progenitor cells (cEPC) have been observed in patients with vascular injury associated with sepsis and acute lung injury. However, a role for cEPC in severe acute pancreatitis (SAP) remains unclear. We therefore conducted a prospective study to study whether the quantities of cEPC can predict persistent organ failure (POF) in patients with predicted SAP. METHODS: A total of 42 predicted SAP patients who were admitted within 24âh after symptom onset and 10 healthy control subjects were enrolled in our study. The proportions of cEPC were analyzed based on flow cytometry simultaneously. Vascular endothelial growth factor (VEGF) levels were measured by enzyme-linked immunosorbent assay. RESULTS: The percentage of cEPC was significantly higher in patients with predicted SAP compared with healthy controls. Similarly, the levels of VEGF in peripheral blood were also significantly higher in predicted SAP patients than in the controls. Notably, patients with POF had lower proportion of cEPC compared with patients with transient organ failure (TOF). In contrast, patients with POF had a significantly higher level of VEGF compared with TOF. Of note, the percentages of cEPC were significantly inversely correlated with disease severity scores. More importantly, cEPC showed an excellent discriminative power for predicting POF among predicted SAP patients, whereas plasma VEGF and disease severity scores showed moderate accuracy in predicting future POF. CONCLUSIONS: Peripheral EPC as a novel biomarker is elevated and may aid to predict the development of POF in patients with predicted SAP.
Subject(s)
Endothelial Progenitor Cells , Multiple Organ Failure/blood , Multiple Organ Failure/etiology , Pancreatitis/blood , Pancreatitis/complications , Acute Disease , Adult , Aged , Biomarkers/blood , Blood Cell Count , Flow Cytometry , Humans , Middle Aged , Prospective StudiesABSTRACT
Central venous catheters (CVCs) are widely used in various puncture and drainage operations in intensive care units (ICUs) in recent years. Compared to conventional operating devices, CVC was welcomed by clinicians because of the advantages of easy use, less damage to the body and convenient fixation process. We came across a patient with severe acute pancreatitis (SAP) who developed cardiac arrest due to thoracic cavity massive bleeding 24 h after thoracocentesis with CVC. Thoracotomy surgery was carried out immediately, which confirmed an intercostal artery injury. The patient was discharged from hospital without any neurological complications two months later. Here we report this case to remind all the emergency department and ICU physicians to pay more attention to the complication of thoracic cavity bleeding following thoracocentesis conducted by CVC.
Subject(s)
Central Venous Catheters , Hemothorax/etiology , Thoracentesis/adverse effects , Adult , Female , Humans , Intensive Care UnitsABSTRACT
BACKGROUND: In the battle against Crohn's disease, autophagy stimulation is a promising therapeutic option-one both new and newly rediscovered. In experimental models, docosahexaenoic acid (DHA)-a long-chain polyunsaturated fatty acid-has been demonstrated to be useful in the treatment of inflammatory bowel disease through inhibition of the nuclear factor-κB pathway. However, the impact of DHA on autophagy in the colon remains unclear. METHODS: Mice were divided into 3 groups: wild type (placebo), the interleukin 10 knockout group (IL-10-/-, placebo), and the DHA group (IL-10-/-, DHA). DHA was administered to IL-10-/- mice by gavage at a dosage of 35.5 mg/kg/d for 2 weeks. The severity of colitis, expression of proinflammatory cytokines, expression/distribution of LC3B, and mTOR signaling pathway were evaluated in the proximal colon tissues collected from all mice at the end of the experiment. RESULTS: DHA administration ameliorated experimental colitis in the IL-10-/- mice, as demonstrated by decreased proinflammatory cytokines (TNF-α and IFN-γ), reduced infiltration of inflammatory cells, and lowered histologic scores of the proximal colon mucosa. Moreover, in the DHA-treated mice, enhanced autophagy was observed to be associated with (1) increased expression and restoration of the distribution integrity of LC3B in the colon and (2) inhibition of the mTOR signaling pathway. CONCLUSION: This study showed that DHA therapy could attenuate experimental chronic colitis in IL-10-/- mice by triggering autophagy via inhibition of the mTOR pathway.
Subject(s)
Autophagy/drug effects , Colitis/drug therapy , Docosahexaenoic Acids/pharmacology , Interleukin-10/deficiency , TOR Serine-Threonine Kinases/genetics , Animals , Chronic Disease , Colon/drug effects , Colon/metabolism , Disease Models, Animal , Interferon-gamma/genetics , Interferon-gamma/metabolism , Interleukin-10/blood , Mice , Mice, Inbred C57BL , Mice, Knockout , Phosphatidylinositol 3-Kinases/genetics , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction , TOR Serine-Threonine Kinases/antagonists & inhibitors , TOR Serine-Threonine Kinases/blood , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolismABSTRACT
BACKGROUND: Enhanced recovery after surgery (ERAS) protocols or fast-track (FT) programs enable a shorter hospital stay and lower complication rate. Minimally invasive surgery (MIS) is associated with a lesser trauma and a quicker recovery in many elective abdominal surgeries. However, little is known of the safety and effectiveness made by ERAS protocols combined with MIS for gastric cancer. The purpose of this study was to evaluate the safety and effectiveness made by FT programs and MIS in combination or alone. METHODS: We summarized an 11-year experience on gastric cancer patients undergoing elective laparotomy or minimally invasive gastric resection in standard cares (SC) or FT programs during January 2004 to December 2014. A total of 984 patients were enrolled and assigned into four groups: open gastrectomies (OG) with SC (OG + SC group, n = 167); OG with FT programs (OG + FT group, n = 277); laparoscopic gastrectomies (LG) with FT programs (LG + FT group, n = 248); and robot-assisted gastrectomies (RG) with FT programs (RG + FT group, n = 292). Patients' data were collected to evaluate the clinical outcome. The primary end point was the length of postoperative hospital stay. RESULTS: The OG + SC group showed the longest postoperative hospital stay (mean: 12.3 days, median: 11 days, interquartile range [IQR]: 6-16 days), while OG + FT, LG + FT, and RG + FT groups recovered faster (mean: 7.4, 6.4, and 6.6 days, median: 6, 6, and 6 days, IQR: 3-9, 4-8, and 3-9 days, respectively, all P< 0.001). The postoperative rehabilitation parameters such as flatus time after surgery (4.7 ± 0.9, 3.1 ± 0.8, 3.0 ± 0.9, and 3.1 ± 0.9 days) followed the same manner. After 30 postoperative days' follow-up, the total incidence of complications was 9.6% in OG + SC group, 10.1% in OG + FT group, 8.1% in LG + FT group, and 10.3% in RG + FT group. The complications showed no significant differences between the four groups (all P > 0.05). CONCLUSIONS: ERAS protocols alone could significantly bring fast recovery after surgery regardless of the surgical technique. MIS further reduces postoperative hospital stay. It is safe and effective to apply ERAS protocols combined with MIS for gastric cancer.
Subject(s)
Postoperative Care/methods , Stomach Neoplasms/surgery , Adult , Aged , Elective Surgical Procedures , Female , Gastrectomy , Humans , Laparoscopy , Length of Stay , Male , Middle Aged , Minimally Invasive Surgical Procedures , Postoperative Complications , Retrospective Studies , Treatment OutcomeABSTRACT
BACKGROUND: Peritoneal air exposure is needed in open abdominal surgery, but long-time exposure could induce intestinal mucosal barrier dysfunction followed by many postoperative complications. High-fat enteral nutrition can ameliorate intestinal injury and improve intestinal function in many gastrointestinal diseases. In the present study, we investigated the effect of high-fat enteral nutrition on intestinal mucosal barrier after peritoneal air exposure and the underlying mechanism. METHODS: Male adult rats were administrated saline, low-fat or high-fat enteral nutrition via gavage before and after peritoneal air exposure for 3 h. Rats undergoing anesthesia without laparotomy received saline as control. Twenty four hours after surgery, samples were collected to assess intestinal mucosal barrier changes in serum D-lactate levels, intestinal permeability, intestinal tight junction protein ZO-1 and occludin levels, and intestinal histopathology. The levels of malondialdehyde and the activity of superoxide dismutase in the ileum tissue were also measured to assess the status of intestinal oxidative stress. RESULTS: High-fat enteral nutrition significantly decreased the serum D-lactate level and increased the intestinal tight junction protein ZO-1 level when compared to the group treated with low-fat enteral nutrition (P < 0.05). Meanwhile, histopathologic findings showed that the intestinal mucosal injury assessed by the Chiu's score and the intestinal epithelial tight junction were also improved much more in the high-fat enteral nutrition-treated group (P < 0.05). In addition, the intestinal malondialdehyde level was lower, and the intestinal superoxide dismutase activity was higher in the high-fat enteral nutrition-treated group than that in the low-fat enteral nutrition-treated group (P < 0.05). CONCLUSIONS: These results suggest that high-fat enteral nutrition could reduce intestinal mucosal barrier damage after peritoneal air exposure, and the underlying mechanism may be associated with its antioxidative action. Perioperative administration of high-fat enteral nutrition may be a promising intervention to preserve intestinal mucosal barrier function in open abdominal surgery.
Subject(s)
Air , Diet, High-Fat , Enteral Nutrition/methods , Ileum/metabolism , Intestinal Mucosa/metabolism , Laparotomy/adverse effects , Peritoneum , Animals , Biomarkers/metabolism , Ileum/pathology , Intestinal Mucosa/pathology , Male , Perioperative Care/methods , Permeability , Postoperative Complications/etiology , Postoperative Complications/prevention & control , Random Allocation , Rats , Tight Junctions/metabolismABSTRACT
BACKGROUND: Peritoneal air exposure is a common phenomenon in abdominal surgery, but long-term exposure could induce intestinal inflammatory responses, resulting in delayed recovery of gastrointestinal motility after surgery. High-fat enteral nutrition has been reported to ameliorate inflammation in many diseases. In the present study, we investigated whether high-fat enteral nutrition could control intestinal inflammation and improve intestinal motility after peritoneal air exposure. METHODS: Male adult rats were administrated saline, low-fat enteral nutrition, or high-fat enteral nutrition via gavage before and after peritoneal air exposure for 3 h. Control rats underwent anesthesia without laparotomy and received saline. Intestinal motility was assessed 24 h after surgery by charcoal transport assay; systemic inflammation was assessed by analyzing serum levels of tumor necrosis factor α, interleukin (IL)-1ß, IL-6, and IL-10; and intestinal inflammation was assessed by analyzing myeloperoxidase activity and concentrations and gene expression of tumor necrosis factor α, IL-1ß, IL-6, and IL-10 in the intestinal tissue. RESULTS: Peritoneal air exposure decreased intestinal motility significantly compared with the control group (P < 0.05). The systemic and intestinal inflammatory parameters were also much higher in the peritoneal air exposure groups than in the control group. Both low-fat and high-fat enteral nutrition increased intestinal motility and reduced systemic and intestinal inflammatory parameter levels to different degrees. However, high-fat enteral nutrition significantly improved the negative alterations in these biochemical parameters compared with low-fat enteral nutrition (P < 0.05). CONCLUSIONS: These results suggest that high-fat enteral nutrition might be able to control intestinal inflammation and improve intestinal motility after peritoneal air exposure. Thus, the perioperative administration of high-fat enteral nutrition may be a promising treatment to enhance the recovery of intestinal motility after surgery.
Subject(s)
Dietary Fats/therapeutic use , Enteral Nutrition , Enteritis/prevention & control , Gastrointestinal Motility , Postoperative Complications/prevention & control , Animals , Cytokines/metabolism , Intestinal Mucosa/metabolism , Male , Peroxidase/metabolism , Random Allocation , Rats, Sprague-DawleyABSTRACT
AIM: To describe the application of complete robotic gastrectomy with transvaginal specimen extraction (TVSE) for gastric cancer patients. METHODS: Between July and November 2014, eight female patients who were diagnosed with gastric adenocarcinoma underwent a TVSE following a full robot-sewn gastrectomy. According to the tumor location, the patients were allocated to two different groups; two patients received robotic total gastrectomy with TVSE and the other six received robotic distal gastrectomy with TVSE. RESULTS: Surgical procedures were successfully performed in all eight cases without conversion. The mean age was 55.3 (range, 42-69) years, and the mean body mass index was 23.2 (range, 21.6-26.0) kg/m(2). The mean total operative time and blood loss were 224 (range, 200-298) min and 62.5 (range, 50-150) mL, respectively. The mean postoperative hospital stay was 3.6 (range, 3-5) d. The mean number of lymph nodes resected was 23.6 (range, 17-27). None was readmitted within 30 d of postoperation. During the follow-up, no stricture developed nor was any anastomotic leakage detected. CONCLUSION: It is possible to perform a TVSE following a full robot-sewn gastrectomy with standard D2 lymph node resection for female gastric cancer patients.
Subject(s)
Adenocarcinoma/surgery , Gastrectomy/methods , Natural Orifice Endoscopic Surgery/methods , Stomach Neoplasms/surgery , Vagina , Adenocarcinoma/secondary , Adult , Aged , Blood Loss, Surgical , Female , Gastrectomy/adverse effects , Humans , Length of Stay , Lymph Node Excision , Lymphatic Metastasis , Middle Aged , Natural Orifice Endoscopic Surgery/adverse effects , Operative Time , Robotic Surgical Procedures/adverse effects , Stomach Neoplasms/pathology , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND: Cordyceps sinensis (C. sinensis), a traditional Chinese medicine, exhibits various pharmacological activities such as reparative, antioxidant, and apoptosis inhibitory effects. Intestinal barrier dysfunction plays a vital role in the progression of sepsis. We aimed to explore the effect of C. sinensis on the gut barrier and evaluate its efficacy in sepsis. METHODS: A murine model of gut barrier dysfunction was created by intraperitoneal injection of endotoxin. C. sinensis or saline was administered orally after the induction of sepsis. Alterations of intestinal barrier were evaluated and compared in terms of epithelial cell apoptosis, proliferation index (PI), intercellular tight junction (TJ) and proliferating cell nuclear antigen (PCNA). RESULTS: C. sinensis significantly decreased the percentage of apoptotic cells and promoted mucosal cells proliferation indicated by enhanced PI and PCNA expression in the intestinal mucosa compared to control group. The TJs between epithelial cells which were disrupted in septic rats were also restored by treatment of C. sinensis. In survival studies, C. sinensis was demonstrated to confer a protection against the lethal effect of sepsis. CONCLUSION: These results suggest that C. sinensis has gut barrier-protection effect in endotoxin-induced sepsis by promoting the proliferation and inhibiting the apoptosis of intestinal mucosal cells, as well as restoring the TJs of intestinal mucosa. C. sinensis may have the potential to be a useful adjunct therapy for sepsis.
ABSTRACT
A defect in the intestinal barrier is one of the characteristics of Crohn's disease (CD). The tight junction (TJ) changes and death of epithelial cells caused by intestinal inflammation play an important role in the development of CD. DHA, a long-chain PUFA, has been shown to be helpful in treating inflammatory bowel disease in experimental models by inhibiting the NF-κB pathway. The present study aimed at investigating the specific effect of DHA on the intestinal barrier function in IL-10-deficient mice. IL-10-deficient mice (IL-10(-/-)) at 16 weeks of age with established colitis were treated with DHA (i.g. 35.5 mg/kg per d) for 2 weeks. The severity of their colitis, levels of pro-inflammatory cytokines, epithelial gene expression, the distributions of TJ proteins (occludin and zona occludens (ZO)-1), and epithelial apoptosis in the proximal colon were measured at the end of the experiment. DHA treatment attenuated the established colitis and was associated with reduced infiltration of inflammatory cells in the colonic mucosa, lower mean histological scores and decreased levels of pro-inflammatory cytokines (IL-17, TNF-α and interferon-γ). Moreover, enhanced barrier function was observed in the DHA-treated mice that resulted from attenuated colonic permeability, rescued expression and corrected distributions of occludin and ZO-1. The results of the present study indicate that DHA therapy may ameliorate experimental colitis in IL-10(-/-) mice by improving the intestinal epithelial barrier function.
Subject(s)
Colitis/drug therapy , Docosahexaenoic Acids/administration & dosage , Interleukin-10/genetics , Intestines/drug effects , Animals , Apoptosis , Colitis/pathology , Disease Models, Animal , Inflammatory Bowel Diseases/drug therapy , Interferon-gamma/metabolism , Interleukin-10/deficiency , Interleukin-17/metabolism , Intestinal Mucosa/drug effects , Intestinal Mucosa/metabolism , Mice , Mice, Inbred C57BL , Mice, Knockout , NF-kappa B/antagonists & inhibitors , NF-kappa B/genetics , NF-kappa B/metabolism , Occludin/genetics , Occludin/metabolism , Tumor Necrosis Factor-alpha/metabolism , Zonula Occludens-1 Protein/genetics , Zonula Occludens-1 Protein/metabolismABSTRACT
BACKGROUND/AIMS: The aim of this study was to report on the feasibility of esophagojejunostomy reconstruction using a robot-sewing technique during a completely robotic total gastrectomy for gastric cancer. METHODOLOGY: Between May 2011 and July 2012, 65 patients in whom gastric adenocarcinoma was diagnosed underwent a completely robotic total gastrectomy, including a robot-sewing esophagojejunal anastomosis. We demonstrated the surgical techniques with analysis of clinicopathologic data and short-term surgical outcomes. RESULTS: All robotic surgeries were successfully performed without conversion. Among the 65 patients, 46 were men and 19 were women. The mean age (± SD) was 57.8 ± 6.5 y. The mean total operative time (± SD), EJ anastomosis time (± SD), and blood loss (± SD) were 245 ± 53 min, 45 ± 26 min, and 75 ± 50 ml, respectively. The mean (± SD) post-operative hospital stay was 5.4 ± 2.5 d. One patient was readmitted for an intestinal obstruction and underwent re-operation 14 d post-operatively; he recovered uneventfully and was discharged 10 d post- operatively. During the follow-up, no patients developed an esophgojejunostomy stricture. CONCLUSIONS: A robot-sewing anastomosis for esophagojejunostomy reconstruction during robotic total gastrectomy for gastric cancer is feasible. Indeed, a robot-sewing anastomosis for esophagojejunostomy reconstruction may become a standard surgical technique during completely robotic total gastrectomy for gastric cancer.
Subject(s)
Adenocarcinoma/surgery , Esophagostomy/methods , Gastrectomy/methods , Jejunostomy/methods , Robotics , Stomach Neoplasms/surgery , Surgery, Computer-Assisted , Suture Techniques , Adenocarcinoma/pathology , Blood Loss, Surgical , Equipment Design , Esophagostomy/adverse effects , Esophagostomy/instrumentation , Feasibility Studies , Female , Gastrectomy/adverse effects , Gastrectomy/instrumentation , Humans , Intestinal Obstruction/etiology , Intestinal Obstruction/surgery , Jejunostomy/adverse effects , Jejunostomy/instrumentation , Length of Stay , Male , Middle Aged , Operative Time , Reoperation , Robotics/instrumentation , Stomach Neoplasms/pathology , Surgery, Computer-Assisted/adverse effects , Surgery, Computer-Assisted/instrumentation , Surgical Equipment , Suture Techniques/adverse effects , Suture Techniques/instrumentation , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND: Celastrol had been proved effective in the treatment for IBD, probably with the modulation of oxidative stress, inflammatory cytokines and intestinal homeostasis. This study was aimed to investigate whether celastrol could ameliorate the inflammation of IL-10 deficient mice, a murine model of Crohn's disease (CD) with the induction of autophagy. MATERIAL AND METHODS: The mice included were divided into four groups, ##WT group, IL-10(-/-) group, Cel group and Control group (celastrol+3-Methyladenine). Celastrol (2 mg/kg) treatment by gavage was administered to mice daily over one week. 3-Methyladenine (autophagy inhibitors) was administered at a dose of 30 mg/kg by intraperitoneal injection. The histological evaluation of the colon, tissue myeloperoxidase (MPO), and colon inflammation of mice in the four groups was evaluated and compared. Furthermore, the PI3K/Akt/mTOR pathway and the status of autophagy in intestine affected by celastrol were also assessed. RESULTS: The one-week administration of celastrol ameliorated established colitis in IL-10 deficient mice, associated with a reduction of marked histological inflammation, a decreased colon MPO concentration and suppression of colonic proinflammatory cytokine. Furthermore, the decreased neutrophil infiltration in proximal colon and improvement of inflammation in the Cel group was much more obvious than that in the Control group. The Western blotting analysis of the PI3K/Akt/mTOR pathway and autophagy showed that celastrol treatment up-regulated the autophagy of colon tissue by suppressing the PI3K/Akt/mTOR signaling pathway. CONCLUSIONS: Celastrol ameliorates experimental colitis in IL-10 deficient mice via the up-regulation of autophagy by suppressing the PI3K/Akt/mTOR signaling pathway.
Subject(s)
Anti-Inflammatory Agents/therapeutic use , Autophagy/drug effects , Colon/drug effects , Crohn Disease/drug therapy , Interleukin-10/deficiency , Triterpenes/therapeutic use , Animals , Anti-Inflammatory Agents/administration & dosage , Blotting, Western , Colon/immunology , Colon/pathology , Crohn Disease/immunology , Crohn Disease/pathology , Disease Models, Animal , Enzyme-Linked Immunosorbent Assay , Interleukin-10/genetics , Mice, Inbred C57BL , Mice, Knockout , Pentacyclic Triterpenes , Peroxidase/metabolism , Real-Time Polymerase Chain Reaction , Signal Transduction/drug effects , TOR Serine-Threonine Kinases/antagonists & inhibitors , Triterpenes/administration & dosageABSTRACT
OBJECTIVES: Activation of "nicotinic anti-inflammatory pathway" could reduce severity of inflammation and injury induced by acute pancreatitis. However, the role of regulatory T (Treg) cells in this pathway is unclear. METHODS: Severe acute pancreatitis (SAP) was induced in mice through retrograde injection of 50-µL 2% Na-taurocholate into the pancreatic duct of the mouse. In nicotine treatment group, nicotine (50, 100, and 300 µg/kg) was administered 1 hour before and after SAP operation through intraperitoneal injection. We compared the properties of Treg cell percentage and specific marker such as cytotoxic T-lymphocyte antigen 4 and forkhead box transcription factor forkhead/winged helix transcription factor p3 on Treg using quantitative reverse transcription polymerase chain reaction and flow cytometry. All experiment animal serum cytokines were measured using enzyme-linked immunosorbent assay. One-way analysis of variance was applied to evaluate the experimental data and for statistical comparisons. The survival rate data were analyzed using the log-rank test. RESULTS: Nicotine significantly protected mice from lethal SAP in a dose-dependent fashion by inhibiting tissue injury, digestive enzyme production, and proinflammatory cytokines production. Moreover, nicotine up-regulated the number and suppressive capacity of CD4 CD25 Treg via inducing the expression of immunoregulatory molecules and transforming growth factor ß1 elevation. CONCLUSIONS: Modulating immunoregulation of CD4 CD25 Treg is a critical mechanism for nicotinic anti-inflammatory pathway and it may be feasible to use selective agonists as an immunotherapy for SAP.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Interleukin-2 Receptor alpha Subunit/metabolism , Nicotine/pharmacology , Pancreas/drug effects , Pancreatitis, Acute Necrotizing/prevention & control , T-Lymphocytes, Regulatory/drug effects , Animals , Biomarkers/metabolism , Cytokines/blood , Cytoprotection , Disease Models, Animal , Dose-Response Relationship, Drug , Inflammation Mediators/blood , Male , Mice, Inbred C57BL , Pancreas/immunology , Pancreas/metabolism , Pancreas/pathology , Pancreatitis, Acute Necrotizing/blood , Pancreatitis, Acute Necrotizing/chemically induced , Pancreatitis, Acute Necrotizing/immunology , Pancreatitis, Acute Necrotizing/pathology , Phenotype , Severity of Illness Index , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/metabolism , Taurocholic Acid , Time FactorsABSTRACT
Surgery is associated with elevated morbidity and mortality in chronic radiation enteritis (CRE). The objective of this study was to evaluate the effect of a fast-track clinical pathway (CP) on postoperative outcomes in patients undergoing ileal/ileocecal resection for CRE with intestinal obstruction. There were 85 patients with CRE (January 2011 to March 2013) with intestinal obstruction admitted to our department for ileal/ileocecal resection. The patients were divided into a prepathway group and a pathway group. The clinical outcomes were then assessed and compared. The postoperative lengths of hospital stay were 8.52 days for the pathway group and 11.32 days for the prepathway group (P = 0.02). The pathway group had a lower stoma rate (21.6 vs 56%, P = 0.033) and fewer postoperative moderate to severe complications (8.1 vs 25%, P = 0.043) compared with the prepathway group. Implementation of the CP may reduce stoma rate, postoperative moderate to severe complications, and postoperative length of hospital stay for patients undergoing ileal/ileocecal resection for the treatment of CRE with intestinal obstruction.
Subject(s)
Critical Pathways , Enteritis/etiology , Enteritis/surgery , Intestinal Obstruction/surgery , Radiation Injuries/surgery , Female , Humans , Ileocecal Valve/surgery , Intestinal Obstruction/etiology , Length of Stay , Male , Middle Aged , Nutrition Assessment , Outcome and Process Assessment, Health Care , Radiation Injuries/complications , Radiotherapy/adverse effectsABSTRACT
BACKGROUND: Alemtuzumab has been used in organ transplantation and a variety of hematologic malignancies (especially for the treatment of B-cell chronic lymphocytic leukemia). However, serious infectious complications frequently occur after treatment. The reason for increased infections postalemtuzumab treatment is unknown at this stage. We explore the effect of alemtuzumab on intestinal intraepithelial lymphocytes (IELs) and intestinal barrier function in cynomolgus model to explain the reason of infection following alemtuzumab treatment. METHODS: Twelve male cynomolguses were randomly assigned to either a treatment or control group. The treatment group received alemtuzumab (3 mg/kg, intravenous injection) while the control group received the same volume of physiological saline. Intestinal IELs were isolated from the control group and the treatment group (on day 9, 35, and 70 after treatment) for counting and flow cytometric analysis. Moreover, intestinal permeability was monitored by enzymatic spectrophotometric technique and enzyme-linked immunosorbent assay. RESULTS: The numbers of IELs were decreased significantly on day 9 after treatment compared with the control group (0.35 ± 0.07 × 10 8 and 1.35 ± 0.09 × 10 8 , respectively; P < 0.05) and were not fully restored until day 70 after treatment. There were significant differences among four groups considering IELs subtypes. In addition, the proportion of apoptotic IELs after alemtuzumab treatment was significantly higher than in the control group (22.01 ± 3.67 and 6.01 ± 1.42, respectively; P < 0.05). Moreover, the concentration of D-lactate and endotoxin was also increased significantly on day 9 after treatment. CONCLUSIONS: Alemtuzumab treatment depletes lymphocytes in the peripheral blood and intestine of cynomolgus model. The induction of apoptosis is an important mechanism of lymphocyte depletion after alemtuzumab treatment. Notably, intestinal barrier function may be disrupted after alemtuzumab treatment.