Perioperative Immune Response Research Articles

Intraoperative cell salvage: The impact on immune cell numbers.

Patient outcomes are influenced by many confounding factors peri-operatively, including the type of surgery, anaesthesia, transfusion, and immune competence. We have previously demonstrated (in-vitro) that compared to allogeneic blood transfusion (ABT), intraoperative cell salvage (ICS) improves immune competence. The peri-operative immune response is complex. Altered or impaired immune responses may predispose patients to develop adverse outcomes (i.e., post-operative wound infection, pneumonia, urinary tract infection etc.) Surgical patients may develop infection, even without the confirmed presence of a definite microbiological pathogen. With all these factors in mind it is important to consider changes in immune cell numbers (and sub-populations) and functional capacity during peri-operative transfusion. In this TRIMICS-Cell (Transfusion Related Immune Modulation and Intraoperative Cell Salvage-Cell numbers) study (n = 17, October 2018-November 2019) we prioritized and analysed peri-operative changes in the number and proportions of immune cell populations and sub-populations (B cells (CD20+), NK (natural killer) cells (CD56+), monocytes (CD14+), T cells (total CD3+ and sub-populations: T helper cells (CD4+), cytotoxic T cells (CD8+), effector T cells (CD4+ CD127+), activated effector T cells (CD4+ CD25+ CD127+) and regulatory T cells (CD4+ CD25+ CD127-)), plasmacytoid dendritic cells (pDC; Lineage-, HLA-DR+, CD11c-, CD123+), classical dendritic cell (cDC) (Lineage-, HLA-DR+, CD11c+), and cDC activation (Lineage-, HLA-DR+, CD11c+), co-stimulatory/adhesion molecules and pDC (CD9+, CD38+, CD80+, CD83+, CD86+, CD123+). Firstly we analysed the whole cohort of study patients and secondly according to the relevant transfusion modality (i.e., three study groups: those who received no transfusion, received ICS only (ICS), or both ICS and allogeneic packed red blood cells (pRBC) (ICS&RBC)), during major orthopaedic surgery. For the whole study cohort (all patients), changes in immune cell populations were significant: leucocytes and specifically neutrophils increased post-operatively, returning towards pre-operative numbers by 48h post-operatively (48h), and lymphocytes reduced post-operatively returning to pre-operative numbers by 48h. When considering transfusion modalities, there were no significant peri-operative changes in the no transfusion group for all immune cell populations studied (cell numbers and proportions (%)). Significant changes in cell population numbers (i.e., leucocytes, neutrophils and lymphocytes) were identified in both transfused groups (ICS and ICS&RBC). Considering all patients, changes in immune cell sub-populations (NK cells, monocytes, B cells, T cells and DCs) and functional characteristics (e.g., co-stimulation markers, adhesion, activation, and regulation) were significant peri-operatively and when considering transfusion modalities. Interestingly DC numbers and functional capacity were specifically altered following ICS compared to ICS&RBC and pDCs were relatively preserved post-operatively following ICS. A transient peri-operative alteration with recovery towards pre-operative numbers by 48h post-surgery was demonstrated for many immune cell populations and sub-populations throughout. Immune cell sub-populations and functional characteristics were similar peri-operatively in those who received no transfusion but changed significantly following ICS and ICS&RBC. Interesting changes that require future study are a post-operative monocyte increase in the ICS&RBC group, changes in cDC considering transfusion modalities, and possibly preserved pDC numbers post-operatively following ICS. Future studies to assess changes in immune cell sub-populations, especially during peri-operative transfusion, while considering post-operative adverse outcomes, is recommended.

Targeted immune activation in pediatric solid tumors: opportunities to complement local control approaches.

Surgery or radiation therapy is nearly universally applied for pediatric solid tumors. In many cases, in diverse tumor types, distant metastatic disease is present and evades surgery or radiation. The systemic host response to these local control modalities may lead to a suppression of antitumor immunity, with potential negative impact on the clinical outcomes for patients in this scenario. Emerging evidence suggests that the perioperative immune responses to surgery or radiation can be modulated therapeutically to preserve anti-tumor immunity, with the added benefit of preventing these local control approaches from serving as pro-tumorigenic stimuli. To realize the potential benefit of therapeutic modulation of the systemic response to surgery or radiation on distant disease that evades these modalities, a detailed knowledge of the tumor-specific immunology as well as the immune responses to surgery and radiation is imperative. In this Review we highlight the current understanding of the tumor immune microenvironment for the most common peripheral pediatric solid tumors, the immune responses to surgery and radiation, and current evidence that supports the potential use of immune activating agents in the perioperative window. Finally, we define existing knowledge gaps that limit the current translational potential of modulating perioperative immunity to achieve effective anti-tumor outcomes.

Pancreatic Cancer and Microenvironments: Implications of Anesthesia.

Simple SummaryPancreatic cancer is a lethal malignant neoplasm with less than 10% 5-year relative survival after the initial diagnosis. Several factors may be related to the poor prognosis of pancreatic cancer, including the rapid tumor progression, increased metastatic propensity, insignificant symptoms, shortage of early diagnostic biomarkers, and its tendency toward resistance to both chemotherapy and radiotherapy. Pancreatic neoplastic cells interact intimately with a complicated microenvironment that can foster drug resistance, metastasis, or relapse in pancreatic cancer. In addition, evidence shows that perioperative factors, including surgical manipulation, anesthetics, or analgesics, might alter the tumor microenvironment and cancer progression. This review outlines the up-to-date knowledge of anesthesia implications in the pancreatic microenvironment and provides future anesthetic strategies for improving pancreatic cancer survival. Pancreatic malignancy is a lethal neoplasm, as well as one of the leading causes of cancer-associated mortality, having a 5-year overall survival rate of less than 10%. The average life expectancy of patients with advanced pancreatic cancer does not exceed six months. Although surgical excision is a favorable modality for long-term survival of pancreatic neoplasm, metastasis is initially identified in nearly 80% of the patients by the time of diagnosis, making the development of therapeutic policy for pancreatic cancer extremely daunting. Emerging evidence shows that pancreatic neoplastic cells interact intimately with a complicated microenvironment that can foster drug resistance, metastasis, or relapse in pancreatic cancer. As a result, the necessity of gaining further insight should be focused on the pancreatic microenvironment contributing to cancer progression. Numerous evidence reveals that perioperative factors, including surgical manipulation and anesthetics (e.g., propofol, volatile anesthetics, local anesthetics, epidural anesthesia/analgesia, midazolam), analgesics (e.g., opioids, non-steroidal anti-inflammatory drugs, tramadol), and anesthetic adjuvants (such as ketamine and dexmedetomidine), might alter the tumor microenvironment and cancer progression by affecting perioperative inflammatory or immune responses during cancer surgery. Therefore, the anesthesiologist plays an important role in perioperative management and may affect surgical outcomes. However, the literature on the impact of anesthesia on the pancreatic cancer microenvironment and progression is limited. This review summarizes the current knowledge of the implications of anesthesia in the pancreatic microenvironment and provides future anesthetic strategies for improving pancreatic cancer survival rates.

Infants with Down syndrome and congenital heart disease have altered peri-operative immune responses

BackgroundInfants with Down syndrome (DS) have an altered immune response. We aimed to characterise the inflammatory response in infants with DS and congenital heart disease (CHD) peri-operatively in comparison to infants with CHD and a normal chromosomal complement, and to healthy infants pre-operatively.MethodsInfants with DS/CHD, infants without DS but with CHD (CHD only) and healthy infants were prospectively recruited and serial serum cytokines evaluated peri-operatively using multiplex ELISA: tumour necrosis factor (TNF)-α and TNF-β; interferon (IFN)-γ, interleukin (IL)-1α, IL-2, IL-6, IL-8, IL-18, IL-1β, IL-10, and IL-1ra; vascular endothelial growth factor (VEGF); granulocyte macrophage colony-stimulating factor (GM-CSF); and erythropoietin (EPO).ResultsNinety-four infants were recruited including age-matched controls (n = 10), DS/CHD (n = 55), and CHD only (n = 29). Children with DS/CHD had significantly lower concentrations of several cytokines (IL-10, IL-6, IL-8, IL-1β, VEGF) in the pre- and post-operatively vs CHD only and controls. EPO and GM-CSF were significantly higher in DS/CHD (p value <0.05).ConclusionsChildren with DS/CHD had significantly lower concentrations of several cytokines compared to controls or children with CHD only. EPO and GM-CSF were significantly higher in children with DS/CHD. The assessment of the immune response may be suitable for the predictable clinical outcomes in these children.ImpactThis study demonstrated that children with Down syndrome (DS) and congenital heart disease (CHD) have significant alterations in pro-inflammatory and anti-inflammatory immune responses peri-operatively.These changes may contribute to adverse clinical outcomes, including sepsis, chylothorax, and autoimmunity. They may impact the pathogenesis and outcome post-operatively and long term in this population.Children with DS and CHD have significantly lower cytokine concentrations, increased EPO and GM-CSF, and decreased VEGF pre- and post-operatively. Assessing their inflammatory state peri-operatively may facilitate the development of a predictive model that can inform tailored management of these infants using novel therapies including immunomodulation.

Effets du sulfonate de sodium carbazochrome combiné à l’acide tranexamique sur l’hémostase et l’inflammation pendant la période périopératoire de l’arthroplastie totale de la hanche: un essai contrôlé randomisé

BackgroundThe hemostatic effect of tranexamic acid (TXA) combined with carbazochrome sodium sulfonate (CSS) in total hip arthroplasty (THA) has not been determined. Therefore we performed a randomized study aiming to evaluate the effects of CSS combined with TXA on perioperative blood loss and inflammatory response of THA. HypothesisCSS combined with TXA can effectively reduce perioperative blood loss and immune response compared to TXA. Material and methodsThis randomized placebo-controlled trial assigned 150 patients undergoing unilateral primary total hip arthroplasty who underwent direct anterior approach surgery to 3 groups: group A received TXA plus topical CSS; group B received TXA only; and group C received placebo. The main outcome was total blood loss. Secondary outcomes included reduction in hemoglobin concentration, coagulation parameters, inflammatory marker levels, perioperative visual analog scale (VAS) pain score, transfusion rates, postoperative hospital stay, and incidence of thromboembolic events. ResultsTotal blood loss in group A (668.84±230.95mL) was lower than in group B (940.96±359.22mL) and C (1166.52±342.85mL, p<0.05). We also found that compared with group B, postoperative hip pain, biomarker level of inflammation, visual analogue score (VAS) pain score in group A were significantly improved. The transfusion rate and unit of group A were significantly lower than group C (8 patients; 17.5 units), but there was no statistical difference between group A (no transfusion) and group B (2 patients; 4 units). No differences were observed in thromboembolic and other outcomes among the groups. DiscussionThe combined application of topic CSS and TXA is more effective than TXA alone following THA in regard of reducing total blood loss. In addition, CSS combined with TXA is better than TXA alone in terms of improving postoperative hip pain and reducing the level of inflammatory factors. Level of evidenceI; randomized controlled study.

THE EFFECT OF REGIONAL VS. GENERAL ANESTHESIA ON THE IMMUNE RESPONSE IN BREAST CANCER SURGERY: A NARRATIVE REVIEW OF THE LITERATURE.

For breast cancer patients, surgery remains the cornerstone in treatment. Perioperative and postoperative period is associated with impaired immune function that can have profound implications for cancer patients in terms of tumor recurrence and metastases. The three main factors include surgery and related neuroendocrine stress response, anesthetic drugs, including opioid analgesics and postoperative pain. The most investigated immune cells are natural killer (NK) cells that are affected by both anesthesia and surgery. It has been demonstrated that ketamine, thiopental, volatile anesthetics, fentanyl and morphine, but not propofol, remifentanil or tramadol reduce the number of circulating NK cells and depress their toxicity. The level of NK cells' cytotoxicity is inversely proportional to the stage and spread of cancer. Regional anesthesia and its potential beneficial effects on the perioperative immune response and long-term outcome after surgery has been investigated as an alternative to general anesthesia in patients undergoing breast cancer surgery. In this paper, we present a review of literature aimed to assess the impact of regional anesthesia techniques on the immune response in patients undergoing breast cancer surgery and how it compares to general anesthesia.

Effects of carbazochrome sodium sulfonate combined with tranexamic acid on hemostasis and inflammation during perioperative period of total hip arthroplasty: A randomized controlled trial

BackgroundThe hemostatic effect of tranexamic acid (TXA) combined with carbazochrome sodium sulfonate (CSS) in total hip arthroplasty (THA) has not been determined. Therefore we performed a randomized study aiming to evaluate the effects of CSS combined with TXA on perioperative blood loss and inflammatory response of THA. HypothesisCSS combined with TXA can effectively reduce perioperative blood loss and immune response compared to TXA. Material and methodsThis randomized placebo-controlled trial assigned 150 patients undergoing unilateral primary total hip arthroplasty who underwent direct anterior approach surgery to 3 groups: group A received TXA plus topical CSS; group B received TXA only; and group C received placebo. The main outcome was total blood loss. Secondary outcomes included reduction in hemoglobin concentration, coagulation parameters, inflammatory marker levels, perioperative visual analog scale (VAS) pain score, transfusion rates, postoperative hospital stay, and incidence of thromboembolic events. ResultsTotal blood loss in group A (668.84±230.95ml) was lower than in group B (940.96±359.22ml) and C (1166.52±342.85ml, p<0.05). We also found that compared with group B, postoperative hip pain, biomarker level of inflammation, visual analogue score (VAS) pain score in group A were significantly improved. The transfusion rate and unit of group A were significantly lower than group C (8 patients; 17.5 units), but there was no statistical difference between group A (no transfusion) and group B (2 patients; 4 units). No differences were observed in thromboembolic and other outcomes among the groups. DiscussionThe combined application of topic CSS and TXA is more effective than TXA alone following THA in regard of reducing total blood loss. In addition, CSS combined with TXA is better than TXA alone in terms of improving postoperative hip pain and reducing the level of inflammatory factors. Level of evidenceI; randomized controlled study.

The postoperative peak number of leukocytes after hepatectomy is a significant prognostic factor for cholangiocarcinoma.

Cholangiocarcinoma (CCA) is a lethal disease. A new predictive factor to identify patients suitable for adjuvant chemotherapy is needed. The relationship between the long-term prognosis and the perioperative immune responses in patients with CCA remains unclear. We therefore investigated the clinical impact of perioperative immune responses on the long-term prognosis in patients receiving hepatectomy for CCA. We investigated 81 patients who underwent hepatectomy between February 2000 and October 2012: 57 intra-hepatic CCA (iCCA) patients and 24 extra-hepatic CCA (eCCA) patients. We checked the postoperative level of C-reactive protein and the numbers of leukocytes. A multivariate analysis of the clinicopathological factors identified 2 significant risk factors for the overall survival: The postoperative maximum number of leukocytes (PNL) among patient factors (P=0.0406) and the TNM-stage among tumor factors (P=0.0059). On evaluating the distribution of each kind of leukocyte with a multivariate analysis, both the postoperative maximum number of neutrophils (PNN) and the postoperative maximum number of eosinophils (PNE) were detected as significant factors among leukocytes (PNN/PNE, P=0.0367/0.0083). In conclusion, the PNL after hepatectomy was significantly associated with the long-term prognosis in patients with CCA. Changes in the numbers of leukocytes after hepatectomy may be a marker on treatment for CCA.

Effects of laparoscope-assisted Ivor-Lewis surgery on perioperative stress, immune responses and intestinal barrier function in elderly patients with esophageal cancer

Objective To analyze the effects of laparoscope-assisted Ivor-Lewis surgery on perioperative stress, immune responses and intestinal barrier function in elderly patients with esophageal cancer. Methods A prospective study including 55 elderly esophageal cancer patients undergoing laparoscope-assisted Ivor-Lewis surgery(the treatment group, n=25)and Ivor-Lewis surgery(the control group, n=25)was conducted.The white blood cell count, neutrophil-to-lymphocyte ratio, percentages of CD4 and CD8 cells, CD4/CD8 ratio, C reactive protein(CRP)and D-lactic acid levels were compared between the two groups before and at 1, 4 and 7 d after operation. Results The white blood cell count(t=2.689, P=0.010)and neutrophil-to-lymphocyte ratio(t=3.300, P=0.002)were lower in the treatment group than in the control group at 1 d after operation.The percentage of CD4 cells was higher in the treatment group than in the control group at 1 d(t=2.242, P=0.029)and 4 d(t=2.031, P=0.047)after operation.The percentage of CD8 cells was higher in the treatment group than in the control group at 1 d after operation(t=2.041, P=0.046). The CD4/CD8 ratio was higher in the treatment group than in the control group at 1 d(t=2.833, P=0.007)and 4 d(t=2.111, P=0.036)after operation.The CRP level was lower in the treatment group than in the control group at 1 d(t=2.267, P=0.028)and 4 d(t=2.111, P=0.036)after operation.The D-lactic acid level was lower in the treatment group than in the control group at 1 d(t=2.267, P=0.028), 4 d(t=7.967, P<0.01)and 7 d(t=2.541, P=0.014)after operation. Conclusions Laparoscope-assisted Ivor-Lewis surgery has good protective effects on perioperative stress, immune responses and intestinal barrier function in elderly patients with esophageal cancer. Key words: Esophageal neoplasms; Laparoscopic; Immunity

Effects of propofol and sevoflurane on perioperative immune response in patients undergoing laparoscopic radical hysterectomy for cervical cancer.

The aim of this study is to compare the effects of propofol and sevoflurane anesthesia on perioperative immune response in patients undergoing laparoscopic radical hysterectomy for cervical cancer.Sixty patients with cervical cancer scheduled for elective laparoscopic radical hysterectomy under general anesthesia were randomized into 2 groups. TIVA group received propofol induction and maintenance and SEVO group received sevoflurane induction and maintenance. Blood samples were collected at 30 min before induction (T0); the end of the operation (T1); and 24 h (T2), 48 h (T3), and 72 h (T4) after operation. The T lymphocyte subsets (including CD3+ cells, CD4+ cells, and CD8+ cells) and CD4+/CD8+ ratio, natural killer (NK) cells, and B lymphocytes were analyzed by flow cytometry.After surgery, all immunological indicators except CD8+ cells were significantly decreased in both groups compared to basal levels in T0, and the counts of CD3+ cells, CD4+ cells, NK cells, and the CD4+/CD8+ ratios were significantly lower in the SEVO groups than that in the TIVA group. However, the numbers of B cells were comparable at all the time points between 2 groups.Laparoscopic radical hysterectomy for cervical cancer is associated with postoperative lymphopenia. In terms of protecting circulating lymphocytes, propofol is superior to sevoflurane.

Does major surgery induce immune suppression and increase the risk of postoperative infection?

Infection is the commonest cause of a postoperative complication. Following major surgery alterations in immune function are commonplace and these may contribute to an enhanced susceptibility to acquire nosocomial infections. This review will discuss postoperative infections in the context of an altered perioperative immune response and the factors influencing this response. Up to 10% of patients undergoing elective in-patient surgery may develop a postoperative infection. Laboratory advances now permit systematic monitoring of single-cell immune signatures, which enable a clearer description of the interaction between tissue damage, immune modulation and clinical outcomes. Traditional candidate gene expression has identified pathways that define the detrimental immune modulating effects of perioperative allogeneic blood transfusion. Large clinical studies have demonstrated that the choice of anaesthetic technique may have an impact on postoperative infections through differential immune modulation. Point of care tests are emerging that allow monitoring of the perioperative immune response. These could be further developed to introduce personalised care pathways. Consideration must also be given to anaesthesia techniques and perioperative treatments that may be associated with poor outcomes through immune modulation.

The perioperative immune response.

A host of immune modulators are now available in clinical practice. The perioperative period is characterized by profound alterations in host immunity, which can result in poor outcomes, which include infection, cancer recurrence and organ failure. Manipulation of the perioperative immune response has the potential to improve outcomes. A complete understanding of the mechanisms and clinical consequences of altered immune function in this setting is therefore imperative. Recent in-vivo data have emerged which further our understanding of the interaction between tissue damage, immune modulation and clinical outcomes by utilizing novel laboratory techniques capable of monitoring single-cell immune signatures. Traditional gene expression assays have continued to demonstrate their utility and have been instrumental in defining the host response to perioperative allogeneic blood transfusion. These mechanistic studies are complemented by large clinical studies describing associations between anaesthetic modalities and immune-related outcomes. Laboratory techniques are now available that can monitor the perioperative immune response and could be further developed to introduce personalized care pathways. Consideration must also be given to anaesthesia techniques and perioperative treatments that, although not immediately harmful, may be associated with poor outcomes temporally distant from the treatment, secondary to induced immunosuppression.

Cellular immunity following video-assisted thoracoscopic and open resection for non-thymomatous myasthenia gravis

Myasthenia gravis (MG) is a common chronic disorder of neuromuscular transmission, frequently treated surgically. Little is known about perioperative cellular immune responses following video-assisted thoracoscopic surgery (VATS) when compared with open resection. Between January and December 2009, 127 patients with non-thymomatous MG underwent surgery, with 54 undergoing VATS and 73 undergoing conventional trans-sternal extended thymectomy (TS). Operative details, ectopic thymic tissue findings, postoperative concentrations of serum immunoglobulin and complement components as well as T-cell immunity were compared in the VATS and TS groups. There were no between-group differences in patients' age, gender, preoperative duration of MG and operation time. Patients who underwent VATS had a lower rate of postoperative stay in the intensive care unit (P = 0.02), less blood loss (P = 0.01) and a lower probability of ectopic thymic tissue. Prominent cellular immunity difference occurred in serum IgG and C3 concentrations and CD4(+) and CD8(+) T-cell counts between the VATS and TS groups. In VATS patients, serum IgG concentration increased slightly on postoperative days 1 and 3. C3 concentration increased gradually in both groups after surgery, but decreased by postoperative day 7. CD4(+) and CD8(+) T-cell counts were relatively stable postoperatively in the VATS group, but were markedly increased in the TS group on postoperative days 1 and 3, with CD4(+), but not CD8(+), T-cells declining on postoperative day 7. VATS for non-thymomatous MG has short-term advantages, with less effect on cellular immune responses than open resection.

Improving Outcome After Major Surgery

Surgical and anesthesia-related techniques may reduce physical stress for patients undergoing high-risk surgery, but major surgery is increasingly performed in patients with substantial comorbidities. Strategies for improving the outcome for such patients include approaches that both increase tissue oxygen delivery and reduce metabolic demand. However, these strategies have produced conflicting results. To understand the success and failure of attempts to improve postoperative outcome, the pathophysiology of perioperative hemodynamic, metabolic, and immunological alterations should be analyzed. Our aim in this review is to provide a survey of fields of opportunities for improving outcome after major surgery. The issues are approached from 3 different angles: the view of the patient, the view of the surgical intervention, and the view of the anesthesia. Special attention is also given to what could be considered the result of the interaction among the 3: perioperative inflammation and immune response.

Effect of thoracic epidural blockade, remifentanil and clonidine on pain and perioperative immune response in patients undergoing lung resection

Effect of thoracic epidural blockade, remifentanil and clonidine on pain and perioperative immune response in patients undergoing lung resection

Reduced perioperative immune response in video-assisted versus open surgery in a rat model

To establish the best technique for thoracoscopic pneumonectomy in the rat and to analyze the differences in perioperative immune response between open and video-assisted thoracoscopic surgery (VATS) in a rat model. The four experimental groups studied were as follows: VATS pneumonectomy, open pneumonectomy, thoracoscopic observation, and open observation. We measured the immunocyte counts and serum cytokine levels postoperatively in each group. The CD3+, CD4+, and CD8+ lymphocyte counts were decreased significantly 12-24 h postoperatively in all groups. Immunosuppression peaked later in the open approach groups than in the VATS groups. The interleukin-6 level was significantly higher in the open approach groups than in the VATS groups. From the viewpoint of immunity, in this rat model VATS was less invasive than open surgery, and open surgery caused greater immunosuppression than VATS, irrespective of organ resection.

Perioperative immune responses in cancer patients undergoing digestive surgeries

BackgroundTh1/Th2 cell balance is thought to be shifted toward a Th2-type immune response not only by malignancy but also by surgical stress. The aim of this study was to estimate perioperative immune responses with respect to the Th1/Th2 balance in patients with gastrointestinal cancer.MethodsNinety-four patients who underwent abdominal surgeries were divided into three groups: gastric resection (n = 40), colorectal resection (n = 34) and hepatic resection (n = 20). Twelve patients undergoing laparoscopic cholecystectomy and 20 healthy subjects were served as control groups. Intracellular cytokine staining in CD4+ T lymphocytes was identified to characterize Th1/Th2 balance. Th1/Th2 balance was evaluated before operation and until postoperative days (POD) 14.ResultsThe preoperative Th1/Th2 ratio was significantly lower in patients with malignancy compared with control. The Th1/Th2 ratio of patients in all groups decreased significantly postoperatively. Th1/Th2 balance on POD 2 in patients with malignancy was significantly decreased compared to patients with laparoscopic cholecystectomy, but there were no significant differences among the four groups on POD 14.ConclusionPatients with malignancy showed an abnormal perioperative Th1/Th2 balance suggesting predominance of a type-2 immune response. Major abdominal surgeries induce a marked shift in Th1/Th2 balance toward Th2 in the early postoperative stage.

Effect of Retroperitoneal Laparoscopic Radical Nephrectomy of Renal Carcinoma (Nephroma) on Perioperative Cell Immunity

To determine perioperative cellular immune responses to retroperitoneal laparoscopic radical nephrectomy by comparing them with those to open radical nephrectomy. Fifty-two patients with renal cell carcinoma were equally randomized into two groups: laparoscopic nephrectomy group (LN group) and open nephrectomy group (ON group) to compare differences in cellular immunofunction. The peripheral blood lymphocyte subpopulations (CD3, CD4, CD8, CD25, CD69, Fas/FasL) were detected with flow cytometry. All tests were performed before operation and at 1, 3, and 5 days after operation. All data were assessed by repeated measurement and variance analysis t test and chi(2) tests. CD3 and CD4 levels in the ON group decreased significantly 1 day and 3 days after operation but recovered on day 5; CD8 level (5 days after operation) in the ON group was significantly higher than that in the LN group. CD25 level (3 days after operation) in the LN group was significantly higher than that in the ON group. CD69 level 3 days after operation in the ON group was significantly higher than that in the LN group. In the ON group, CD69 increased markedly 3 days after operation. FasL level (in both the LN and ON groups) was higher than the normal reference; Fas and FasL in the ON group were higher than those in the LN group. The perioperative immune response is less obvious after a laparoscopic procedure compared with a conventional approach in patients with renal cell carcinoma.

Perioperative stress response in dogs undergoing elective surgery: variations in behavioural, neuroendocrine, immune and acute phase responses

AbstractThe aim of this trial was to describe the behavioural, neuroendocrine, immune and acute phase stress responses in dogs undergoing elective surgery in normal, clinical practice conditions. Sixteen dogs were submitted to elective orchiectomy or ovariohysterectomy using a standardised surgical protocol. Each animal was confined to the Intensive Care Unit during pre- and post-surgery and perioperative behavioural, neuroendocrine, immune and acute phase responses were studied. Behavioural categories, cortisol, prolactin, white blood cell, C-reactive protein and haptoglobin variation were evaluated. Values at different times were compared with basal values shown by the dog in its usual environment. Communicative and explorative behaviours showed high occurrence pre-surgery and were inhibited post-surgery. Decreases in post-surgery activity, interactive behaviours and changes in waking/sleeping patterns were observed. The most sensitive marker of psychological stress, cortisol, in comparison with basal values, showed a significant increase both during pre- and post-surgery confinement in the ICU cage. Prolactin values were characterised by a significant decrease early into the post-surgery period. The immune response was characterised by long-term neutrophilia and monocytosis, but by short-term lymphopaenia and eosinopaenia, limited to the early post-operative period. With regard to the acute phase response, both C-reactive protein and haptoglobin showed a long-term increase, post-surgery. Changes in behavioural, haematological and biochemical markers showed that perioperative stress represents a major challenge to dog welfare.

Perioperative cell-mediated immune response

Innate and acquired immunity play a pivotal role in the host defense response. Pain, surgical stress, tissue injury and invasive micro-organisms are known to modulate complex immune responses in patients undergoing major surgery, which can lead to subsequent increased susceptibility to postoperative infections. Anesthetics may influence the immune response indirectly through modulation of the neurohumoral response or directly by acting on immune competent cells. In particular, cell-mediated immune balance seems to be affected by anesthetics and this might account for anesthetic-dependant risk of postoperative infections. Consequently, in order to fully understand the immunomodulating properties and ensuing clinical relevance of anesthetics it will be necessary to investigate each agent individually and in a variety of clinical settings. The existing research in this field, most of which is experimental, has yielded different results. The goal of further clinical studies must be to establish the immunomodulating properties of individual anesthetic agents so that selection can be tailored to the individual patient's pre-operative immune status and intraoperative course.