Impact of Preoperative Immunonutrition on Perioperative Outcomes following Cystectomy.

PURPOSE: Radical cystectomy (RC) for the management of muscle-invasive bladder cancer remains a morbid procedure with high rates of perioperative complications. The role of preoperative immunonutritional supplementation (pre-INS) in improving post-RC outcomes is promising and needs further validation. MATERIALS AND METHODS: We performed a retrospective review of 204 patients who underwent RC for bladder cancer at a single institution, comparing patients who received oral L-arginine-based pre-INS, and those who did not. Preoperative features, postoperative complications, and readmission data were collected. Outcomes of interest included development of high-grade (Clavien-Dindo III-V) complications, readmission within 30 days, ileus, total parenteral nutrition (TPN) requirement, postoperative infection, and length of stay (LOS). Categorical and continuous outcomes were assessed using Fisher's exact test and Welch T-test, respectively. Multivariable logistic regression (MLoR) analysis was used to identify predictive factors for our outcomes. RESULTS: Patients who received pre-INS had significantly lower odds of requiring postoperative TPN (17.3% vs 35.6%; Fisher p=0.015, OR=0.38) and developing postoperative infection (25% vs 45%; Fisher p=0.003; OR=0.41) but no significant difference in the rates of other outcomes. On MLoR, when adjusting for age, gender, body mass index, Charlson comorbidity index, undergoing neoadjuvant chemotherapy and operative features, pre-INS was a significant predictor of postoperative infection (Fisher p=0.02; OR=0.35) but not for high-grade complications, readmission, ileus, needing TPN or LOS. CONCLUSIONS: Preoperative immunonutrition with an L-arginine-based supplement is associated with significant reduction in postoperative infection, one of the most common complications of RC.

Clinical, randomized, double blind clinical trial to study the effect of parenteral supplementation with fish oil emulsion in the nutritional support in esophagectomized patients.

INTRODUCTION: Esophagectomy is a major surgery with a high degree of catabolic and post-surgical inflammatory response accompanied by high morbidity and significant mortality. Post-surgical nutritional support via enteral administration of ω-3 fatty acids has been seen to be effective although its bad tolerance. There are few clinical trials with parenteral ω-3 fatty acids in these patients. We propose to investigate the effect of combining a parenteral fish oil lipid emulsion with the standard enteral nutrition (EN) support. MATERIALS AND METHODS: Prospective, single-center, randomized, double-blind study in esophagectomized patients, and treated after surgery with parenteral lipid emulsions of ω-3 fatty acids or a mixture of ω-6 long-chain triglycerides/short-chain triglycerides 50%. These emulsions will be added to the standard nutritional support in continuous infusion until 5 days of treatment have been completed. Patients will be randomized 1:1:1 in Group A receiving 0.4 g/kg/d of fish-oil lipid emulsion and 0.4 g/kg/d of a lipid emulsion mixture of ω-6 long-chain fatty acids (LCT) plus medium-chain fatty acids (MCT) (total dose of 0.8 g/kg/d of lipid emulsion); Group B receiving 0.8 g/kg/d of fish oil lipid emulsion and Group C receiving 0.8 g/kg/d of LCT/MCT emulsion.The main objective is to determine whether 5 days administration of intravenous ω-3 fatty acid lipid emulsion is effective in normalizing interleukin-6 levels compared with LCT/MCT emulsions, and whether a 0.8 g/kg/d dose is more effective than 0.4 g/kg/d. Secondary outcomes include other inflammatory markers such as C-reactive protein, tumor necrosis factor alpha and interleukin-10, and parameters of morbidity, safety, nutrition and mortality.Samples will be collected at the time when surgery is indicated and on days 0, 1, 3, 5 and 21 to determine inflammatory, nutritional, hepatic and safety parameters. In addition, clinical follow-up will be continued throughout the hospital admision and up to 1 year after surgery. DISCUSSION: Studies of ω-3 fatty acids administered parenterally in esophagectomized patients are scarce. This study proposes to investigate the effect of combining fish-oil lipid emulsions administered parenterally with EN support. Potential benefits include fast incorporation of lipids to the cellular membranes and to the inflammatory cascade, and the use of only 1 pharmaconutrient. TRIAL REGISTRATION: FAR-NP-2017-01 EudraCT number: 2016-004978-17.https://reec.aemps.es/reec/public/detail.html searching the EudraCT number. VERSION IDENTIFIER: Version 2, 08/06/2017.

[de la evidencia y algoritmo adaptado Immunonutrition in fast-track surgical patients - Evidence review and adapted algorithm]. / Inmunonutrición del paciente quirúrgico en los procedimientos fast-track: revisión de la evidencia y algoritmo adaptado.

INTRODUCTION: Surgical stress predisposes patients to have immune dysfunction and an increased risk of infection. Malnourished surgical patients have higher postoperative morbidity and mortality rates, higher readmission rates, and higher hospital costs. The use of an immunomodulatory formula is associated in the ESPEN guidelines with a reduction in wound healing problems, suture failure, and infectious and global complications. Several authors have suggested that, since most clinical trials evaluating the efficacy of immunonutrition have been carried out in a traditional perioperative setting, it would be interesting to investigate its efficacy in a more controlled setting, such as in the ERAS (Enhanced Recovery after Surgery) protocol. The objective of this work was: a) to define the role that immunonutrition should play in ERAS protocols based on the best scientific evidence available; b) to analyze the difficulties that continue to exist in real-life clinical practice to screen the nutritional risk of patients; c) to make a proposal of algorithms adapted to the characteristics of our environment regarding the screening, assessment, and nutritional treatment of surgical patients in fast-track surgery.

INTRODUCCIÓN: El estrés quirúrgico predispone a los pacientes a la disfunción inmune y a un mayor riesgo de infección. Los pacientes quirúrgicos desnutridos presentan una mayor morbimortalidad posoperatoria, mayores tasas de reingreso y costes hospitalarios más elevados. En las guías de la ESPEN se asocia el uso de una fórmula inmunomoduladora a una reducción significativa de los problemas de la cicatrización de heridas, de los fallos de la sutura y de las complicaciones infecciosas y globales. Varios autores han sugerido que, dado que la mayoría de los ensayos clínicos que evalúan la eficacia de la inmunonutrición se han realizado en un entorno perioperatorio tradicional, sería interesante investigar su eficacia en un entorno más controlado, como en el protocolo ERAS (Enhanced Recovery after Surgery). El objetivo de este trabajo es: a) definir el papel que debe jugar la inmunonutrición en los protocolos ERAS sobre la base de la mejor evidencia científica; b) analizar las dificultades que siguen existiendo en la práctica clínica real para realizar el cribado del riesgo nutricional del paciente; c) proponer unos algoritmos adaptados a las características de nuestro entorno sobre el cribado, la valoración y el tratamiento nutricional del paciente quirúrgico en modalidad fast-track.

The efficacy of early postoperative enteral immunonutrition on T-lymphocyte count: A randomised control study in low-risk cardiac surgery patients.

BACKGROUND: Patients undergoing cardiac surgery have a pronounced immune response that leads to a reduction in cellular immunity. Immune-modulating nutritional supplements are considered to be beneficial for patients undergoing major surgery. However, due to the lack of studies in the cardiac surgery population, the effect of immunonutrition remains unclear in this patient group. OBJECTIVE: Our purpose was to research the efficacy of early postoperative enteral immunonutrition on T-lymphocyte count in the cardiac surgery population. METHODS: This was a randomised control study of low operative risk adult patients, who underwent elective cardiac surgery. These patients were randomised into immunonutrition and control groups. The immunonutrition group was supplemented with immune nutrients for five postoperative days. The counts of T-lymphocytes, as well as the counts for the CD4+ and CD8+ cell subpopulations were determined on the day of surgery and on the sixth postoperative day. RESULTS: Fifty-five patients were enrolled in the study, the mean age was 69.7 ± 6.3 years, 28 (50.9%) of them were males, the median operative risk was 1.75%. Twenty-seven (49.1%) were randomised into the immunonutrition group. The control and the immunonutrition groups were similar before the intervention. The counts of the CD3+ T cells and CD4+ T cells on the sixth postoperative day were significantly higher in the immunonutrition group compared to the control group with 1.42 ± 0.49 vs. 1.12 ± 0.56 (∗109/l), p = 0.035 and 1.02 ± 0.36 vs. 0.80 ± 0.43 (∗109/l), p = 0.048, respectively. Regression analysis was performed to determine the efficacy of the immunonutrition on the counts of the CD3+ and CD4+ T cells; CD3+ T and CD4+ T cell counts were increased to 0.264 (∗109/l), p = 0.039 and 0.232 (∗109/l), p = 0.021, respectively. CONCLUSIONS: Early postoperative immunonutrition increases the count of the CD3+ and CD4+ T cells in cardiac surgical patients. Clinical trials identifier number: NCT04047095.

The Role of Immunonutrition in Patients Undergoing Pancreaticoduodenectomy.

Pancreaticoduodenectomy (PD) is one of the most difficult and complex surgical procedures in abdominal surgery. Malnutrition and immune dysfunction in patients with pancreatic cancer (PC) may lead to a higher risk of postoperative infectious complications. Although immunonutrition (IN) is recommended for enhanced recovery after surgery (ERAS) in patients undergoing PD for 5-7 days perioperatively, its role in patients undergoing pancreatectomy is still unclear and controversial. It is known that the proper surgical technique is very important in order to reduce a risk of postoperative complications, such as a pancreatic fistula, and to improve disease-free survival in patients following PD. However, it has been proven that IN decreases the risk of infectious complications, and shortens hospital stays in patients undergoing PD. This is a result of the impact on altered inflammatory responses in patients with cancer. Both enteral and parenteral, as well as preoperative and postoperative IN, using various nutrients, such as glutamine, arginine, omega-3 fatty acids and nucleotides, is administered. The most frequently used preoperative oral supplementation is recommended. The aim of this paper is to present the indications and benefits of IN in patients undergoing PD.

Transcutaneous Electrical Acupoint Stimulation for Improving Postoperative Recovery, Reducing Stress and Inflammatory Responses in Elderly Patient Undergoing Knee Surgery.

Transcutaneous electrical acupoint stimulation (TEAS) is a form of acupuncture treatment that applies electrical stimulation on specific acupoint through cutaneous electrodes. This technique has been used for perioperative anesthesia management as part of after surgery recovery. However, to date, limited data are available for using the TEAS for postoperative recovery in elderly surgical patients. We conducted this prospective randomized sham-control trail to evaluate the efficacy of TEAS in a group of elderly patients receiving knee surgery under epidural anesthesia. 52 subjects were assigned to either the experimental group (Group E) or control group (Group C). The patients in Group E received TEAS at zusanli (ST36), sanyinjiao (SP6), neiguan (PC6), and quchi acupoints (LI11) 30min prior to the epidural anesthesia and postoperative day 1 and 2, while patients in Group C received sham TEAS on the same acupoints for 30min same as those of Group E. The primary endpoint was the Quality of Recovery-40 questionnaire (QR-40) and the secondary endpoints were the biomarkers level of stress and inflammatory responses and visual analogue scale (VAS). A one-way ANOVA (SNK method) was used in statistic, and p<0.05 is considered to be statistically significant. Our data showed that the QoR-40 was significantly lower in Group C than that in Group E at postoperative day 1 (p<0.05); Similarly, Cortisol (COR), Adrenocorticotropic Hormone (ACTH), and C-reactive protein (CRP) were significantly lower in Group E than those of Group C at postoperative day 1, 3, and 7 (p<0.05), while the neutrophil/lymphocyte ratio (N/L) was lower in Group E than that in Group C at postoperative day 1 and 3 (p<0.05). Our results showed that perioperative TEAS administration is able to facilitate the development of postoperative recovery of elderly patients, especially at the early stage after surgery. The reported results are likely to be mediated by the reduction of surgical inflammation and perioperative stress response.

Fluoroquinolones for the treatment of latent Mycobacterium tuberculosis infection in liver transplantation.

Solid organ transplantation (SOT) is the best treatment option for end-stage organ disease. Newer immunosuppressive agents have reduced the incidence of graft rejection but have increased the risk of infection, particularly due to the reactivation of latent infections due to opportunistic agents such as Mycobacterium tuberculosis. Active tuberculosis (TB) after SOT is a significant cause of morbidity and mortality. Most cases of posttransplant TB are secondary to reactivation of latent tuberculosis infection (LTBI) due to the effects of long-term immunosuppressive therapy. Risk minimization strategies have been developed to diagnose LTBI and initiate treatment prior to transplantation. Isoniazid with vitamin B6 supplementation is the treatment of choice. However, liver transplantation (LT) candidates and recipients have an increased risk of isoniazid-induced liver toxicity, leading to lower treatment completion rates than in other SOT populations. Fluoroquinolones (FQs) exhibit good in vitro antimycobacterial activity and a lower risk of drug-induced liver injury than isoniazid. In the present review, we highlight the disease burden posed by posttransplant TB and summarize the emerging clinical evidence supporting the use of FQs for the treatment of LTBI in LT recipients and candidates.

Possible anti-inflammatory role of Zingiberis processum rhizoma, one component of the Kampo formula daikenchuto, against neutrophil infiltration through muscarinic acetylcholine receptor activation.

Zingiberis processum rhizoma (ZPR) is a major active component of daikenchuto (DKT), which induces anti-inflammatory action by inhibiting macrophage infiltration. However, it is unclear whether ZPR is related to DKT-induced anti-inflammatory action via a reduction of neutrophil infiltration against postoperative ileus (POI). In this study, we orally administered individual herbal components of DKT to mice four times before and after intestinal manipulation (IM). The anti-inflammatory action of each crude drug was evaluated by histochemical analysis of relevant molecules. The results showed that treatment with all herbal components of DKT significantly inhibits neutrophil infiltration. This inhibition of neutrophil infiltration by ZPR was significantly reduced in 5-hydroxytryptamine receptor 4 (5-HT4R) knockout (KO) mice but not in alpha-7 nicotinic acetylcholine receptor (α7nAChR) KO mice. Also, transient receptor potential ankyrin 1 (TRPA1) and muscarinic acetylcholine receptor (mAChR) antagonists partly and significantly inhibited the amelioration of neutrophil infiltration by ZPR. Therefore, DKT-induced anti-inflammatory action, mediated by inhibition of neutrophil infiltration in POI, depends, in part, on the effects of ZPR. ZPR activates TRPA1 channels, possibly in enterochromaffin (EC) cells, to release 5-HT. This 5-HT stimulates 5-HT4R in the myenteric plexus neurons to release acetylcholine, which, in turn, activates mAChR to inhibit inflammation in POI.

Perioperative Immunonutrition Modulates Inflammatory Response after Radical Cystectomy: Results of a Pilot Randomized Controlled Clinical Trial.

PURPOSE: Poor preoperative nutritional status is associated with a higher complication rate after radical cystectomy in patients with bladder cancer. Given the short interval between diagnosis and radical cystectomy, we compared the effect of short-term specialized immunonutrition to that of a standard oral nutritional supplement on the acute inflammatory response and arginine status in patients treated with radical cystectomy. MATERIALS AND METHODS: In this prospective, randomized study in 29 men 14 received specialized immunonutrition and 15 received oral nutritional supplement. Each group drank 3 cartons per day for 5 days before and 5 days after radical cystectomy. The Th1-Th2 balance, plasma interleukin-6 and plasma amino acids were measured at baseline, intraoperatively and on postoperative days 2, 14 and 30. Body composition was measured by dual energy x-ray absorptiometry at baseline and on postoperative days 14 and 30. Differences in outcomes were assessed using the generalized linear mixed model. RESULTS: In the specialized immunonutrition group there was a 54.3% average increase in the Th1-Th2 balance according to the tumor necrosis factor-α-to-interleukin-13 ratio from baseline to intraoperative day, representing a shift toward a Th1 response. In the oral nutritional supplement group the Th1-Th2 balance decreased 4.8%. The change in the Th1-Th2 balance between the specialized immunonutrition and oral nutritional supplement groups significantly differed (p <0.027). Plasma interleukin-6 was 42.8% lower in the specialized immunonutrition group compared to the oral nutritional supplement group on postoperative day 2 (p = 0.020). In the specialized immunonutrition group plasma arginine was maintained from baseline to postoperative day 2 and yet the oral nutritional supplement group showed a 26.3% reduction from baseline to postoperative day 2 (p = 0.0003). The change in appendicular muscle loss between the groups was not statistically significant. CONCLUSIONS: Th1-to-Th2 ratios, peak interleukin-6 levels and plasma arginine suggest that consuming specialized immunonutrition counteracts the disrupted T-helper balance, lowers the inflammatory response and prevents arginine depletion due to radical cystectomy.

Intravenous fish oil in critically ill and surgical patients - Historical remarks and critical appraisal.

The purpose of this review is to explain the historical and clinical background for intravenous fish oil administration, to evaluate its results by using a product specific metaanalysis, and to stimulate further research in the immune-modulatory potential of fish oil. Concerning the immune-modulatory effects of fatty acids, a study revealed that ω-3 as well as ω-6 fatty acids would prolong transplant survival, and only a mixture with an ω-6:ω-3 ratio of 2.1:1 would give immune-neutral results. In 1998, the label of a newly registered fish oil emulsion also acknowledged this immune-neutral ratio in conjunction with ω-6 lipids. Also, two fish oil-supplemented fat emulsions, registered in 2004, used a similar ω-6:ω-3 ratio. Such an immune-neutral ω-6:ω-3 ratio denoted progress for most patients compared to pure ω-6 lipid emulsions. However, this immune-neutrality might on the other hand be responsible for the limited positive clinical results gained so far in critically ill and surgical patients where in most cases significance could only be shown for the pooled effect of numerous trials. Our product specific metaanalysis also did not reveal any differences, neither in infections rates nor in ICU or hospital length of stay. To evaluate the immune-modulatory effect of fish oil administered alone, new dose finding studies, reporting relevant clinical outcome parameters, are required. Precise mechanistic or physiological biomarkers for the indication of such a therapy should also be developed and validated.

Effects of parenteral ω-3 fatty acid supplementation in postoperative gastrointestinal cancer on immune function and length of hospital stay: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Omega-3 fatty acids are widely used in nutritional support. However, whether parenteral supplementation with ω-3 fatty acids is effective for gastrointestinal cancer patients remains uncertain. This study assessed the effects of this form of parenteral nutrition on immune function and clinical outcomes in postoperative gastrointestinal cancer patients. METHODS AND STUDY DESIGN: We searched Medline, Embase, Scopus, and the reference lists of selected studies to identify randomized controlled trials that compared ω-3 fatty acids with a control, and that included immune indices, infectious complications, or length of hospital stay in the final outcomes. The odds ratio and weighted mean difference with 95% confidence intervals were calculated and the I2 statistic was used to assess heterogeneity. RESULTS: Seven trials with a total of 457 participants were included in the meta-analysis. Five pooled trials with 373 participants indicated that the incidence of infectious complications was significantly different between the intervention and control groups (odds ratio: 0.36; 95% confidence interval: 0.18, 0.74, p<0.05). Five trials involving 385 participants indicated that parenteral ω-3 fatty acid supplementation significantly shortened the length of hospital stay (weighted mean difference: -2.29, 95% confidence interval: -3.64, -0.93; p<0.05). Meta-analysis also indicated that ω-3 fatty acids increased the level of CD4+ and CD4+/CD8+ ratio. CONCLUSIONS: The results of this study suggest that parenteral ω-3 fatty acid supplementation is beneficial for gastrointestinal cancer patients, and is accompanied by improved postoperative immune function and satisfactory clinical outcomes.

Preoperative immunonutrition prior to radical cystectomy: a pilot study.

INTRODUCTION: To investigate the use of a high-arginine immunonutrient supplement prior to radical cystectomy for bladder cancer. MATERIALS AND METHODS: We recruited 40 patients to consume a total of four high-arginine immunonutrient shakes per day for 5 days prior to radical cystectomy. The primary outcome measures were safety, tolerability and adherence to the supplementation regimen. Ninety-day postoperative outcomes were also compared between supplemented patients and a cohort of 104 prospectively identified non-supplemented radical cystectomy patients. Multivariable logistic regression models were used to compare overall complications, infectious complications, and readmission rates between groups. RESULTS: There were no serious adverse events during supplementation. Four patients (10%) stopped supplementation due to nausea (n = 2) and bloating (n = 2). Thirty-three patients (83%) consumed all prescribed shakes. Immunonutrient supplementation was not significantly associated with overall complications (adjusted odds ratio [OR] 1.08; 95% confidence interval [CI] 0.50-2.33), infectious complications (OR 1.23; 95% CI 0.49-3.07), or readmissions (OR 1.48; 95% CI 0.62-3.51) on multivariable analyses. CONCLUSIONS: Preoperative supplementation with a high-arginine immunonutrient shake was safe and well tolerated prior to radical cystectomy. Contrary to prior reports, immunonutrient supplementation was not associated with lower postoperative infectious complications in this cohort, perhaps owing to the 5 day supplementation period. Further study is needed to identify the optimal immunonutrient supplement regimen for radical cystectomy patients.

Nutrition and Immune-Modulatory Intervention in Surgical Patients With Gastric Cancer.

This study evaluated the effect of an immune-modulatory diet on patients with gastric cancer and identified the parameters associated with postoperative outcomes. This was a single-arm prospective intervention study. At baseline, patients were assessed for nutrition (Patient-Generated Subjective Global Assessment), inflammatory markers (albumin, C-reactive protein, and interleukin 6 [IL-6]), and immune markers (percentage NK, CD4, CD8, and CD4:CD8 ratio); they also received nutrition counseling and high-calorie/protein supplement. A week before surgery, they were assessed for nutrition and inflammatory/immune markers and started on an immune-modulatory supplement until the day before surgery, when they were evaluated again. On the second postoperative day, patients were assessed for inflammatory/immune parameters, and a final nutrition evaluation was performed until the day of discharge. Complications were recorded daily and up to 30 days after discharge. Thirty-seven patients (60 ± 10 years old) were included, and 57% were classified as malnourished. Maintenance of nutrition and immune parameters occurred throughout the study period, but we found a preoperative increase in C-reactive protein (0.1-1.5 mg/dL) and IL-6 (2.0-14.2 pg/mL) and a postoperative increase in the CD4:CD8 ratio (2.3 ± 1.0). Complications and death were seen in 35%, especially patients with higher preoperative IL-6 (2.2-46 pg/mL), lower CD4:CD8 ratio (1.7 ± 0.5), and lower protein (1.2 ± 0.5 g/kg/d) and calorie intake (1552 ± 584 kcal/kg/d). The high-calorie/protein supplementation with the immune-modulating diet was able to maintain the nutrition and immune status of patients with gastric cancer.

Do smokers have greater risk of delayed and non-union after fracture, osteotomy and arthrodesis? A systematic review with meta-analysis.

OBJECTIVES: Systematic review and meta-analysis of published observational cohort studies. To quantify the increased risk smokers have of experiencing a delayed and/or non-union in fractures, spinal fusion, osteotomy, arthrodesis or established non-unions. SETTING: Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica database (EMBASE), Allied and Complementary Medicine Database (AMED) and Web of Science Core Collection from 1966 to 2015. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS AND INTERVENTIONS: Observational cohort studies that reported adult smokers and non-smokers with delayed and/or non-union or time to union of the fracture, spinal fusion, osteotomy, arthrodesis or established non-union were eligible. DATA EXTRACTION AND OUTCOME MEASURES: 2 authors screen titles, abstracts and full papers. Data were extracted by 1 author and checked independently by a second. The relative risk ratios of smoking versus non-smoking and the mean difference in time to union patients developing a delayed and/or non-union were calculated. RESULTS: The search identified 3013 articles; of which, 40 studies were included. The meta-analysis of 7516 procedures revealed that smoking is linked to an increased risk of delayed and/or non-union. When considered collectively, smokers have 2.2 (1.9 to 2.6) times the risk of experiencing delayed and/or non-union. In all the subgroups, the increased risk was always ≥1.6 times that of non-smokers. In the patients where union did occur, it was a longer process in the smokers. The data from 923 procedures were included and revealed an increase in time to union of 27.7 days (14.2 to 41.3). CONCLUSIONS: Smokers have twice the risk of experiencing a non-union after fracture, spinal fusion, osteotomy, arthrodesis or treatment of non-union. Time to union following fracture, osteotomy, arthrodesis or treatment of an established non-union is longer in smokers. Smokers should be encouraged to abstain from smoking to improve the outcome of these orthopaedic treatments.

A role for 12/15-lipoxygenase-derived proresolving mediators in postoperative ileus: protectin DX-regulated neutrophil extravasation.

Resolution of inflammation is an active counter-regulatory mechanism involving polyunsaturated fatty acid-derived proresolving lipid mediators. Postoperative intestinal motility disturbances, clinically known as postoperative ileus, occur frequently after abdominal surgery and are mediated by a complex inflammation of the intestinal muscularis externa. Herein, we tested the hypothesis that proresolving lipid mediators are involved in the resolution of postoperative ileus. In a standardized experimental model of postoperative ileus, we detected strong expression of 12/15-lipoxygenase within the postoperative muscularis externa of C57BL/6 mice, predominately located within CX3CR1(+)/Ly6C(+) infiltrating monocytes rather than Ly6G(+) neutrophils. Mass spectrometry analyses demonstrated that a 12/15-lipoxygenase increase was accompanied by production of docosahexaenoic acid-derived lipid mediators, particularly protectin DX and resolvin D2, and their common precursor 17-hydroxy docosahexaenoic acid. Perioperative administration of protectin DX, but not resolvin D2 diminished blood-derived leukocyte infiltration into the surgically manipulated muscularis externa and improved the gastrointestinal motility. Flow cytometry analyses showed impaired Ly6G(+)/Ly6C(+) neutrophil extravasation after protectin DX treatment, whereas Ly6G(-)/Ly6C(+) monocyte numbers were not affected. 12/15-lipoxygenase-deficient mice, lacking endogenous protectin DX synthesis, demonstrated increased postoperative leukocyte levels. Preoperative intravenous administration of a docosahexaenoic acid-rich lipid emulsion reduced postoperative leukocyte infiltration in wild-type mice but failed in 12/15-lipoxygenase-deficient mice mice. Protectin DX application reduced leukocyte influx and rescued 12/15-lipoxygenase-deficient mice mice from postoperative ileus. In conclusion, our results show that 12/15-lipoxygenase mediates postoperative ileus resolution via production of proresolving docosahexaenoic acid-derived protectin DX. Perioperative, parenteral protectin DX or docosahexaenoic acid supplementation, as well as modulation of the 12/15-lipoxygenase pathway, may be instrumental in prevention of postoperative ileus.

Autoimmune/inflammatory syndrome induced by adjuvant (ASIA) evolution after silicone implants. Who is at risk?

Silicone implants have been in use since the mid-twentieth century, especially in the field of reconstructive breast surgery, and have long been considered as biologically inert and harmless. However, growing body of evidence from the past two decades links silicone with subsequent autoimmunity-related complications, collectively known as autoimmune/inflammatory syndrome induced by adjuvant--ASIA. Previous data suggest that while some patients tend to develop post-exposure autoimmune phenomena such as ASIA, other do not. However, thus far, no criteria for risk stratification were suggested. This current review summarizes the data linking silicone implants and autoimmunity, suggesting means of defining individuals who are at increased risk to develop silicone-induced ASIA, and therefore, a recommendation was made to avoid silicone implantation, e.g., individuals with previously diagnosed autoimmune disorders or with genetic preponderance for hyperactive immune system should not be considered as candidates for silicone implantation.

[IMPROVING THE RESULTS OF SURGICAL TREATMENT OF GALLSTONE DISEASE].

THE PURPOSE OF THE STUDY: optimization measures for postoperative management of patients after laparoscopic cholecystectomy. MATERIAL AND METHODS: In the study group included 102 women and 302 men. At the 303 patients (75%) for specific indications ERCP was performed. Age of patients varied from 16 to 80 years and averaged 47.7 ± 12.9 years. It should be noted that at 298 (98.3%) patients ERCP was performed prior to laparoscopic cholecystectomy with diagnostic or therapeutic purposes. To assess the effectiveness of treatment comparison group (control group) consisted of 20 patients with postoperative complications identified after cholecystectomy; patients received basic diet. Main group--25 patients, where in treatment as an additional therapeutic agent administered vegetables "Hepartea". Liver function was assessed by biochemical studies (total protein, urea, ALT and AST). Were determined the quality of life of patients immediately after surgery and at certain stages of rehabilitation after the application of supportive therapy. RESULTS: According to clinical, laboratory and morphological studies acute cholecystitis abscess was observed at 0.25 ± 0.25%; chronic calculous cholecystitis in 75.7 ± 2.13%. Among the total surveyed hospitalized patients in 16 (5.3%) patients ERCP was performed with diagnostic, and in 287 (94.7%) cases--with curative intent. Statistical analysis of data obtained from the structural components of the SF-36 in 30 days after completion of conservative therapy with herbal preparation revealed some nnormalization of protein metabolism, enzyme activity and other indicators of liver function. CONCLUSION: dates on the main group of the patients noted relatively fast dynamics of normalization of stimulating cell-mediated immunity, evidenced by a more pronounced and significant decrease in protein damage and reduction of urea. Chemical analysis of peripheral blood and clinical trials show greater therapeutic effect of herbal drug when used in the early postoperative period after laparoscopic cholecystectomy. Using herbal drug in treatment of complications of laparoscopic cholecystectomy can effectively stop clinical and biochemical manifestations of inflammation, reduce the incidence of postoperative complications and reduce the time of rehabilitation, which has a significant beneficial impact on the quality of life of patients.

[Kampo Medicine in Perioperative Care for Cancer Patients].

Operative stress causes various changes in the body, and immunological hypofunction and malnutrition increase complications and adversely affect long-term prognosis. Therefore, reducing operative stress as much as possible, minimizing complications after surgery, and aiming for a satisfactory postoperative course are important. However, difficult and unresolvable situations often arise when only the conventional Western medicine approach is used because the situation and condition varies for each patient. We believe that Kampo medicine is very useful in diverse situations. Particularly, Kampo medicine has been used more frequently in recent years, with the expectation of numerous effects, because the effectiveness of Kampo medicine on various disease states has been proven and the pharmacological ingredients and the mechanisms by which Kampo medicine exerts its effects have been better clarified scientifically. Kampo medicine will have an effect in various situations, and we think that Kampo medicine occupies an important position in team-based medical care with multiple specialists. Kampo medicine compounds have been reported to be useful for the following conditions: Hochuekkito and Juzentaihoto for improving immunocompetence after operative stress, Daikenchuto and Rikkunshito for improving postoperative gastrointestinal motility, Shakuyakukanzoto for postoperative wound pain control, Yokukansan for postoperative delirium, and Inchinkoto for postoperative liver dysfunction. The availability of numerous treatment choices that work well in specific situations would be useful for cancer patients during the perioperative period.

Berberine hydrochloride prevents postsurgery intestinal adhesion and inflammation in rats.

Intestinal adhesion, characterized by connection of the loops of the intestine with other abdominal organs by fibrous tissue bands, remains an inevitable event of abdominal operations and can cause a number of complications. Berberine hydrochloride (berberine), a natural plant alkaloid derived from Chinese herbal medicine, is characterized by diverse pharmacological effects, such as anticancer and lower elevated blood glucose. This study is designed to investigate the effects of berberine on adhesion and inflammation after abdominal surgeries and the underlying molecular mechanisms. Adhesion severity grades and collagen deposition were assessed 14 days after surgery. We evaluated the levels of intercellular adhesion molecule-1 (ICAM-1) and inflammatory cytokines interleukin-1ß (IL-1ß), IL-6, transforming growth factor ß (TGF-ß), tumor necrosis factor-α (TNF-α), and examined transforming growth factor-activated kinase 1 (TAK1)/c-Jun N-terminal kinase (JNK) and TAK1/nuclear factor κB (NF-κB) signaling. The surgery group experienced the most severe adhesions, and berberine strikingly reduced the density and severity of adhesion. Results showed significant lower expression of IL-1ß, IL-6, TGF-ß, TNF-α, and ICAM-1, in berberine groups compared with the operation group. Activities of phosphorylated JNK and phosphorylated NF-κB were inhibited in the berberine groups compared with the surgery group. Our novel findings identified berberine hydrochloride as a promising strategy to prevent adhesion by downregulating ICAM-1 and reduce inflammation by inhibiting the TAK1/JNK and TAK1/NF-κB signaling after abdominal surgery, which brought out a good therapeutic approach for the development of clinical application for postoperative abdominal adhesion and inflammation.