Nervous System Diseases

Gland and Hormone Related Diseases

All Conditions

Neoplasms

Pituitary Diseases

Pituitary Neoplasms

Hypothalamic Diseases

Brain Diseases

Central Nervous System Diseases

Endocrine System Diseases

Endocrine Gland Neoplasms

Hypothalamic Neoplasms

Supratentorial Neoplasms

Brain Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Central Nervous System Depressants

All Drugs and Chemicals

Platelet Aggregation Inhibitors

Analgesics

Anticonvulsants

Anesthetics

Propofol

Sevoflurane

Remifentanil

Thiopental

Anesthesia is maintained with propofol during surgery

Anesthesia is maintained with sevoflurane during surgery

In the TIVA group,anesthesia is induced and maintained by effect-site target controlled infusion of propofol and remifentanil.

total intravenous anesthesia (TIVA)

In the inhalation anesthesia group, anesthesia is induced by pentothal sodium 4-6mg/kg and remifentanil 1 μg/kg, and then maintained with end-tidal sevoflurane concentration of 0.8 to 1 MAC and continuous infusion of remifentanil at 0.1-0.3μg/kg/min.

inhalation anesthesia group

A number of studies have compared the effects of total intravenous anesthesia(TIVA) versus inhalational anesthesia on perioperative period during transsphenoidal surgery. However, they have limitations especially for the phase of recovery after anesthesia: a fragmentary assessment. Quality of Recovery 40 (QoR-40) questionnaire was multi-dimensionally designed to assess the degree of recovery, specially after anesthesia and surgery. In this study, the investigators aim to compare the quality of recovery after inhalational anesthesia and after TIVA through QoR-40 questionnaire in patients undergoing transsphenoidal surgery for pituitary tumor under general anesthesia.

Effects of Total Intravenous Anesthesia With Propofol-remifentanil Versus Inhalational Anesthesia With Sevoflurane on Quality of Recovery in Patients Undergoing Transsphenoidal Surgery for Pituitary Tumor

We compare the QoR-40 scores of two groups 1 day after the operation.

Yonsei University

Digestive System Diseases

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Patients in Gradual Goal-dose EN group will receive increased calories gradually by enteral nutrition and will reach the 80% of target energy by enteral nutrition at day 8.

Patients in immediate Goal-dose EN group will reach the 100% of target energy by enteral nutrition at day 3 after abdominal surgery.

Patients in Gradual Goal-dose EN group will receive increased calories gradually by EN and will reach the 80% of target energy by EN at day 8 while patients in immediate Goal-dose EN group will receive 100% of target energy by EN at day 3 after abdominal surgery. Both of the two group will receive EN for 5 days except 80% of target energy delivered by oral feeding or patients are discharged from hospital, whichever arrives first.

Enteral nutrition

Xinying Wang, MD

Patients will be randomized to Gradual or immediate Goal-dose EN group at day 3 after abdominal surgery. Patients will receive Goal-dose EN gradually or immediately after abdominal surgery. Both groups will receive EN for 5 days except 80% of target energy delivered by oral feeding or patients are discharged from hospital. The primary and secondary outcomes will be collected.

Patients after abdominal surgery will receive enteral nutrition for 2 days, if she/he can tolerate 30% of goal-dose EN, then she/he will be randomized to Gradual or immediate Goal-dose EN group at day 3. Patients in Gradual Goal-dose EN group will receive increased calories gradually by EN and will reach the 80% of target energy by EN at day 8 while patients in immediate Goal-dose EN group will receive 100% of target energy by EN at day 3 after abdominal surgery. Both groups will receive EN for 5 days except 80% of target energy delivered by oral feeding or patients are discharged from hospital, whichever arrives first. The primary and secondary outcomes will be collected.

Gradual Versus Immediate Goal-dose Enteral Nutrition in Abdominal Surgery Patients

Gradual Versus Immediate Goal-dose Enteral Nutrition in Abdominal Surgery Patients: A Clinical Randomized Controlled Trial

Invasion of the host organism by microorganisms that can cause pathological conditions or diseases.

The total energy patients received during the intervention.

Diarrhea, vomiting, abdominal distention or cramping and abdominal pain.

Albumin, pre-albumin, transferrin and retinol conjugated protein

All deaths reported in all enrolled patients.

Peking Union Medical College Hospital

Chinese PLA General Hospital

First Affiliated Hospital, Sun Yat-Sen University

Xijing Hospital

West China Hospital

Xinqiao Hospital of Chongqing

Second Affiliated Hospital, School of Medicine, Zhejiang University

Changhai Hospital

Shanghai 10th People's Hospital

The Second Affiliated Hospital of Harbin Medical University

The Affiliated Hospital of Qingdao University

First Affiliated Hospital of Kunming Medical University

Jinling Hospital, China

Professor

Colorectal Neoplasms

Intestinal Neoplasms

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Immunologic Factors

The aim of this study is to characterize the systemic stress response (SSR) induced in patients undergoing colorectal cancer (CRC) surgery. The project is a clinical prospective study. Blood samples will be collected from 30 patients on the day before CRC-surgery, and 1, 2, 3 and 10 days after surgery. A specimen from the resected tumor tissue will also be collected and sent for immunohistochemical analysis. Whole blood gene expression profiling will be performed to gain knowledge of the genetic changes in immunological, inflammatory and oxidative stress-related factors initiated by surgery. Peripheral immunological cells, proteins and cytokines will be analysed by FLOW and ELISA methods, and the functional capacity of NK-cells will also be defined for each time point. Furthermore, tumor tissue will be analyzed for invasion of immunological cells. At each time point, the patients will be asked to fill out a validated patient reported outcome measure with questions concerning clinical outcome parameters related to recovery after CRC-surgery

Background

The perioperative period is relatively short, but highly critical for cancer related survival. The surgical procedure results in release of tumor cells locally and in the blood, and induction of a surgical stress response (SSR). This leads to paralysis of the immune system, reduced clearance of cancer cells and optimal conditions for cancer cells to grow and metastasize(1).

Colorectal cancer (CRC) is the third most common cause of cancer in Denmark. In 2013, 4196 Danish patients were diagnosed with CRC(2) and current standard of care includes a tumour resection. However, even after an expected curative surgical tumour resection, 25-30% will have a relapse within 5 years after the primary procedure.

To improve the outcome after surgery for cancer, it is crucial to understand, in details, how SSR affects the immune response and how SSR affects the ability of cancer cells to grow and metastasize. By performing expression profiling of over 40.000 genes in whole blood before and after surgery, we will obtain a genetic signature of genes from circulating immune cells, including granulocytes, monocytes, B and T cells, dendritic cells, and platelets, which will enable us to see the exact impact surgery has on gene transcription of these immunological factors. By using this information, perioperative interventions can be performed to optimize the immunological response in the perioperative period, leading to reduced risk of cancer recurrence and consequently improved survival (3).

Surgical stress response (SSR) It is well known that a surgical procedure induces a disturbance of the immunological and inflammatory balance, causing a systemic inflammatory response (4), immune suppression (4,5) and excess reactive oxygen species (ROS) (6,7). Systemic inflammation promotes tumor growth (8), and in patients who have undergone potentially curative resection for colorectal cancer, the presence of a systemic inflammatory response predicts a poor outcome (3). The paralysis of the immune system includes reduced activity of NK cells and macrophages, both of which under normal circumstances protects against metastasis by eliminating disseminating tumor cells. Excessive ROS causes DNA damage, break down of extracellular matrix and elimination of cell-cell adhesions (5,6,7). In this way, surgery promotes optimal conditions for cancer cells to grow and metastasize in the post-operative phase. Recent research shows that immune cells and their invasion of the primary tumor correlates to the patient's prognosis, again suggesting that the immune response is important for inhibition of cancer growth(9,10). Detailed information of genetic changes in different factors of the immune response due to surgery remains unclear.

Study design The project consist of a clinical prospective explorative study including 30 patients undergoing elective hemi-colectomy due to colon cancer UICC stadium II-III. Blood samples will be collected on the day prior to surgery, and on post-operative day 1, 2, 3 and 10. Samples will be prepared for Flow cytometric analysis, bio banking, cryopreservation and whole blood genomic profiling.

Whole blood gene expression profiling will be performed and analyzed to determine possible transcriptional changes in genes encoding for immunological, inflammatory and oxidative stress-related factors caused by surgery. It is possible to make both a quantitative as well as qualitative measurement of these genetic changes (11).The probe sets that are found to be the most significantly differentially expressed before and after surgery will be chosen for further analysis. Genes that are significantly deregulated and have been described in previous studies, within the field of inflammation, immunological and oxidative stress, will be chosen for further analysis. Examples of exact genes within immunology and inflammation will be genes encoding for TNFα, IL-1b, IL-2, IL-6, IL-10, VEGF, TGFβ and HLA-G. Within oxidative and antioxidative genes, special emphasis will be taken in FoxO3, TP53 and ATM as inactivation of these are associated with increased levels of ROS. Upregulation of ATOX1, DEFB122 and GBX8 is associated with increased levels of ROS, and will also be chosen for further analysis (19-21).

Alterations in specific inflammatory and immune modulating proteins (TNFα, IL-1b, IL-2, IL-6, IL-10, VEGF, TGFβ and HLA-G), the functional activity of natural killer (NK) cells, and the fractions and absolute numbers of specific sub-populations of immune cells (CD3+CD4+, CD3+CD8+, FoxP3+ / CD4+CD25+CD127 /dim regulatory T cells, CD4+HLA-G+ regulatory T cells, myeloid-derived suppressor cells and NK subsets) will be identified. Results from genetic transcription analysis and analysis of alterations in inflammatory and immune modulating proteins, will be compared in order to give a full overview of the SSR, and the effect of surgery on immunological, oxidative and inflammatory factors, in order to evaluate the potential carcinogenic effect of surgery, and times and methods of optimal intervention in this damaging process.

Tumor samples from the 30 enrolled patients will be analyzed for the level of invasion of immunological cells. The results will be correlated to the results from gene expression profiling and analysis of inflammatory and immune modulating proteins determined in whole blood samples prior to surgery. Immunohistochemistry will be performed and inflammatory invasion of the tumor will be evaluated according to Klintrup's methods (12) and the immunoscore (13). These methods are based on a scoring system defining the deepest point of invasion of inflammatory cells identified from haematoxylin and eosin slides.

Methods

Whole blood gene expression profiling:

Blood samples will be collected in PAX-gene tubes and sent for analysis at Odense University Hospital, Dept. of Clinical Genetics. Total RNA will be extracted using the Paxgene Blood RNA kit (Qiagen, Franklin Lakes, NJ, USA) and quality of RNA will be tested using Agilent 2100 Bioanalyzer (Agilent Technologies, Palo Alto, CA). The Message-AmpTM III RNA amplification kit (Ambion, Austin, TX) will be used to convert total RNA to biotin-labeled aRNA. Labeled aRNA will be hybridized to Affymetrix HGU133 Plus 2.0 chips. Data pre-processing will be done in R environment using robust multi-array average expression measure (rma) to perform background correction, normalization, and expression index calculation of all microarrays. Further high level analysis will include advanced methods for high dimensional data including supervised and unsupervised methods. Fold changes will be calculated and Significance analysis of Microarray (SAM) and t-test will be used to identify differentially expressed genes, samples and correction for multiple hypothesis testing will be performed using FDR method. Pathway analysis will be applied to identify the biological mechanisms activated by the surgical manipulation, using Gene Set Enrichment Analysis (GSEA, Broad Institute).

Assessement of inflammatory and immunological markers:

When all samples have been collected, part of the bio-banked plasma and serum will be used for measurement of concentrations of TNFα, IL-1b, IL-2, IL-6, IL-10, VEGF, TGFβ and HLA-G by ELISAs on a BEP2000 ELISA instrument (Siemens Healthcare, Erlangen, Germany) at Roskilde Hospitals, Dept.of Clinical Biochemistry, where they have a lot of experience with these measures.

Analysis of lekocyte subpopulations:

Multi-color immunophenotyping of leukocyte sub-populations will be performed within 1-2 hours after blood samples have been drawn. Analysis will be done by the use of BD FACS Canto II instruments (BD Biosciences, New Jersey, USA). This instrument analyzes eight colors/markers per tube. By the use of specific marker panels CD3+CD4+, CD3+CD8+, FoxP3+ / CD4+CD25+CD127 /dim regulatory T cells, CD4+HLA-G+ regulatory T cells, myeloid-derived suppressor cells and NK subsets will be identified. Results will be analyzed according to inflammatory and immunological up or down regulation in the period from the day before surgery and up to 10 days after.

Immunohistochemical analysis of tumor specimens:

Immunohistochemistry will be performed when all samples have been collected. Depths of invasion and number of cells expressing CD4, CD8, CD45RO and GZMB will be analyzed. The analysis will be performed according to the Klintrup's methods, which is a scoring method ranging from 0-3. A score of 0 indicates no increase in the inflammatory cells at the deepest point of the tumors invasive margin; 1 indicates a mild and patchy increase; 2 indicates a prominent inflammatory reaction, and 3 denotes a florid cup-like inflammatory infiltrate at the invasive edge with frequent destruction of cancer cell islands. These scores are then classified as low (0 and 1) and high (2 and 3) grade.

NK cells After isolation af cryopreservation of PBMC's, the functional activity of NK cells is determined in vitro by exposing them to chromium labeled NK sensitive target cells. NK cell activity is quantified in this assay by the measurement of chromium released from NK cell lysed targets.

Blood samples for Whole Blood genomic profiling

Immunological and Oxidative Stress Response in Relation to Abdominal Cancer Surgery

The most significantly differentially expressed probe sets will be chosen for further analysis. Examples of exact genes will be genes encoding for TNFα, IL-1b, IL-2, IL-6, IL-10, VEGF, TGFβ and HLA-G. Within oxidative and antioxidative genes, special emphasis will be taken in FoxO3, TP53 and ATM.

TNFα, IL-1b, IL-2, IL-6, IL-10, VEGF, TGFβ and HLA-G, the functional activity of NK-cells, and the fractions and absolute numbers of specific sub-populations of CD3+CD4+, CD3+CD8+, FoxP3+ / CD4+CD25+CD127 /dim regulatory T cells, CD4+HLA-G+ regulatory T cells, myeloid-derived suppressor cells and NK subsets will be identified before and after surgery.

Tumor samples will be analyzed for level of invasion of immunological cells through immunohistrochemistry and definition of the deepest point of invasion of immunological cells according to the Klinstrups methods. The results will be correlated to the results from gene expression profiling and analysis of inflammatory and immune modulating proteins determined before surgery.

Odense University Hospital

Zealand University Hospital

Heart and Blood Diseases

Rare Diseases

Stomach Neoplasms

Thromboembolism

Venous Thromboembolism

Stomach Diseases

Thrombosis

Embolism

Embolism and Thrombosis

Vascular Diseases

Stomach Cancer

Patients receiving gastric cancer surgery will be prospectively observed for the development of venous thromboembolism

Gastric surgery

Venous thromboembolism (VTE) has considerably harmful effects on morbidity and mortality of cancer patients. Several guidelines recommendations have been made about the use of anticoagulation for the prevention and treatment of VTE in Western patients with cancer. In Western VTE guidelines, all solid cancer patients receiving abdominal major surgery are strongly recommended to receive pharmacologic prophylactic anticoagulation such as low molecular weight heparin (LMWH) in the perioperative periods. These guideline recommendations are based on high incidence of postoperative VTE development in Western cancer patients. However, there have been many cumulative data about the effect of different ethnicity on the VTE development and more and more investigators and clinicians admit that Asian ethnicity has lower incidence of VTE than Western ethnicity. Therefore, it may not be advisable to apply Western guidelines as it is to the clinical situation of Asian cancer patients.

Although gastric cancer is the common cancer in Asia, there is no prospective data on the incidence of VTE development during the postoperative period of gastric cancer surgery. In other words, Asian doctors including Korean clinicians don't know the exact incidence of surgery-related VTE. From their clinical experiences, most Korean surgeons think that the incidence of postoperative VTE development is rare. They also have much concern about the complications such as bleeding that might be caused by routine use of pharmacologic thromboprophylaxis during the perioperative periods. Therefore, in most clinical situation, Korean surgeons do not perform perioperative pharmacologic thromboprophylaxis using LMHW. Considering these clinical situations in Korea, the uncritical acceptance of Western guidelines is inappropriate. The necessity of pharmacologic thrombo-prophylaxis can be answered only from the results of the prospective study on the incidence of postoperative VTE development after gastric cancer surgery. Moreover, current surgical trend in cancer patients is minimally invasive approach such as laparoscopic surgery. However, the necessity of pharmacologic thromboprophylaxis in patients receiving laparoscopic cancer surgery has not been evaluated even in Western countries. Western guidelines also cannot exactly answer whether pharmacologic thromboprophylaxis is really necessary in cancer patients receiving laparoscopic cancer surgery. On above backgrounds, this study was designed.

Incidence of Venous Thromboembolism Following Surgery in Patients With Gastric Cancer

Incidence of Venous Thromboembolism Following Surgery in Patients With Gastric Cancer; a Prospective Study

To evaluate the incidence of symptomatic or asymptomatic VTE detected by Doppler venous ultrasound during postoperative periods in patients with gastric cancer receiving surgery

To identify risk factors for the development of VTE in this population

Seoul National University Bundang Hospital

M.D. & Ph.D.

Patients who can not tolerate 30% of target energy EN will receive supplemental parenteral nutrition at day 3 after abdominal surgery.

Patients who can not tolerate 30% of target energy EN will receive supplemental parenteral nutrition at day 8 after abdominal surgery.

Patients who can not tolerate 30% of target energy EN will receive supplemental parenteral nutrition at day 3 or at day 8 after abdominal surgery.

Parenteral Nutrition

Patients will be randomized to early PN group or late PN group at day 3 after abdominal surgery. Patients will receive supplemental parenteral nutrition or not within 7 days after abdominal surgery. Both groups will receive SPN except 80% of target energy delivered by EN or oral or patients are discharged from hospital. The primary and secondary outcomes will be collected.

Patients after abdominal surgery will attempt enteral nutrition support for 2 days, if she/he can not tolerate 30% of target energy, then she/he will be randomized to early PN group or late PN group at day 3. Patients in early PN group will receive supplemental parenteral nutrition at day 3 while patients in late PN group will not receive supplemental parenteral nutrition until day 8 after abdominal surgery. Both groups will receive SPN except 80% of target energy delivered by EN or oral or patients are discharged from hospital. The primary and secondary outcomes will be collected.

Early Versus Delayed Parenteral Nutrition in Abdominal Surgical Patients

Early Versus Delayed Parenteral Nutrition in Abdominal Surgical Patients With Nutritional Risk and Initial Enteral Nutrition Intolerance: A Clinical Randomized Trial

Invasion of the host organism by microorganisms that can cause pathological conditions or diseases

The length of patients stay in hospital after operation

Diarrhea, vomiting, abdominal distention or cramping and abdominal pain

The total energy patients received during the intervention

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Effects of Total Intravenous Anesthesia With Propofol-remifentanil Versus Inhalational Anesthesia With Sevoflurane on Quality of Recovery in Patients Undergoing Transsphenoidal Surgery for Pituitary Tumor	NCT02813044	Pituitary Tumor	total intraveno... inhalation anes...	19 Years -	Yonsei University
Effects of Total Intravenous Anesthesia With Propofol-remifentanil Versus Inhalational Anesthesia With Sevoflurane on Quality of Recovery in Patients Undergoing Transsphenoidal Surgery for Pituitary Tumor	NCT02813044	Pituitary Tumor	total intraveno... inhalation anes...	19 Years -	Yonsei University
Gradual Versus Immediate Goal-dose Enteral Nutrition in Abdominal Surgery Patients	NCT03117348	Enteral Nutriti... Postoperative P... Digestive Syste...	Enteral nutriti...	18 Years - 80 Years	Jinling Hospital, China
Immunological and Oxidative Stress Response in Relation to Abdominal Cancer Surgery	NCT03473327	Colorectal Neop...		18 Years - 75 Years	Zealand University Hospital
Incidence of Venous Thromboembolism Following Surgery in Patients With Gastric Cancer	NCT01345773	Gastric Cancer Venous Thromboe... Postoperative P...	Gastric surgery	20 Years -	Seoul National University Bundang Hospital
Early Versus Delayed Parenteral Nutrition in Abdominal Surgical Patients	NCT03115957	Digestive Syste...	Parenteral Nutr...	18 Years - 80 Years	Jinling Hospital, China

Spots Global Cancer Trial Database for postoperative period