Perioperative Immunonutrition, Phagocytic and Bactericidal Activity of Blood Platelets in Gastric Cancer Patients

Prospective Study of the Effect of Perioperative Immunonutrition on the Immune Host Defense and the Phagocytic and Bactericidal Activity of Blood Platelets in Gastric Cancer Patients.

Perioperative immunonutrition in gastric cancer patients can reduce perioperative morbidity and may improve quality of their life. Patients with gastric cancer will be divided into four groups depending on the type of artificial nutrition. Group I (enteral feeding) and II (enteral feeding and parenteral nutrition with glutamine) will be administered nutritional therapy during the postoperative period, group III (oral arginine) and IV (parenteral immunonutrition) patients will be treated nutritionally both prior to and after the surgery. The lymphocytes and their subpopulations, interleukin IL-1B,-6,-23, and the phagocytic, and bactericidal activity of blood platelets will be determined before and after nutritional therapy.

Study Overview

• Status: Unknown
• Conditions: Gastric Cancer
• Intervention / Treatment: Dietary supplement: Early postoperative enteral nutrition, based on standard elementary diet (Peptisorb); Drug: glutamine; Dietary supplement: oral diet enriched with arginine (Cubitan); Drug: Perioperative parenteral immunonutrition (Dipeptiven, Omegaven)

Detailed Description

Surgical treatment of gastric cancer is associated with a high risk of perioperative complications. Morbidity of cancer patients increases in concert with the clinical stage of the malignancy. It is postulated that a reduction in perioperative morbidity and improved quality of life of patients with advanced gastric cancer can be achieved by proper preparation to surgery, among others. One of such methods is the implementation of immunostimulating nutritional therapy during the perioperative period.The stage of cancer will be graded according to TNM classification. The patients will be randomly assigned to four clinical groups based on the type of nutritional therapy implemented.

• Study Type: Interventional
• Enrollment (Anticipated): 240
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Zbigniew Kamocki, MD PhD; Phone Number: +48606452246; Email: zkamocki@gmail.com

Study Locations

• Poland
  • Podlaskie
    • Bialystok, Podlaskie, Poland, 15089
      • Recruiting
      • Medical University of Bialystok
      • Contact: Zbigniew Kamocki, MD PhD; Phone Number: +48606452246; Email: zkamocki@gmail.com
      • Principal Investigator: Zbigniew Kamocki, MD PhD
      • Sub-Investigator: Joanna Matowicka-Karna, MD PhD
      • Sub-Investigator: Joanna Osada, MD PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• gastric cancer

Exclusion Criteria:

• for group III constituted gastric cancer associated with severe gastrointestinal obstruction

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: I - Nutritional therapy only during the postoperative period.; Postoperative nutritional therapy administered in group I will not include immunomodulating factors. Early postoperative enteral nutrition, based on standard elementary diet (Peptisorb), starts 20 hours post-surgery. The initial flow rate will be 8 ml/h, which will be increased gradually, with the volume doubled every 24 hours, up to 100 ml/h. The enteral nutrition will be continued for six days. During the initial five days post-surgery, the patients will be additionally supplemented parenterally via peripheral veins (commercially available two-chamber bag for peripheral access with 480 kcal of energetic value and 5.7g of N contained in standard amino acids).	Dietary supplement: Early postoperative enteral nutrition, based on standard elementary diet (Peptisorb); Early postoperative enteral nutrition with standard elementary diet (Peptisorb), will start 20 hours post-surgery. The initial flow rate will be 8 ml/h, which will increase gradually, with the volume doubled every 24 hours, up to 100 ml/h. The enteral nutrition wil be continued for six days. During the initial five days post-surgery, the patients will be additionally supplemented parenterally via peripheral veins (commercially available two-chamber bag for peripheral access with 480 kcal of energetic value and 5.7g of N contained in standard amino acids).
Active Comparator: II - parenteral glutamine in postoperative time; The nutritional therapy of group II patients will start post-surgery. It will be based on early enteral nutrition with elementary diet (Peptisorb) with simultaneous parenteral nutrition with two-chamber bag with 480 kcal energetic value and 5.7g of N contained in standard amino acids administered via peripheral veins. Additionally, glutamine (100 ml of Dipeptiven) will be added to the two-chamber bag. The parenteral nutrition will be administered for five days.	Dietary supplement: Early postoperative enteral nutrition, based on standard elementary diet (Peptisorb); Early postoperative enteral nutrition with standard elementary diet (Peptisorb), will start 20 hours post-surgery. The initial flow rate will be 8 ml/h, which will increase gradually, with the volume doubled every 24 hours, up to 100 ml/h. The enteral nutrition wil be continued for six days. During the initial five days post-surgery, the patients will be additionally supplemented parenterally via peripheral veins (commercially available two-chamber bag for peripheral access with 480 kcal of energetic value and 5.7g of N contained in standard amino acids).; Drug: glutamine; The nutritional therapy of group II patients will start post-surgery. It will be based on early enteral nutrition with elementary diet (Peptisorb) with simultaneous parenteral nutrition with two-chamber bag with 480 kcal energetic value and 5.7g of N contained in standard amino acids administered via peripheral veins. Additionally, glutamine (100 ml of Dipeptiven) will be added to the two-chamber bag. The parenteral nutrition will be administered for five days.
Active Comparator: III - perioperative oral immunonutrition; Preoperatively, group III patients will be given commercially available oral diet enriched with arginine (Cubitan, 1 package 3 times per day). Additionally, they will be administered commercially available two-chamber bag with 480 kcal energetic value and 5.7g of N in standard amino acids via peripheral access. The duration of pre-operative preparatory phase ranged between 5 and 10 days (8 days on average). Enteral nutrition with commercially available arginine-containing diet (Cubison) will start 20 hours post-surgery at an 8 ml/h flow rate; the rate will be increased gradually, with the volume doubled every 24 hours, up to 100 ml/h and continued for six days. Simultaneously, commercially available two-chamber bags for peripheral access with composition identical to that used preoperatively will be administered via peripheral veins for five days.	Dietary supplement: oral diet enriched with arginine (Cubitan); Preoperatively, group III patients will be given commercially available oral diet enriched with arginine (Cubitan, 1 package 3 times per day). Additionally, they were administered commercially available two-chamber bag with 480 kcal energetic value and 5.7g of N in standard amino acids via peripheral access. The duration of pre-operative preparatory phase ranged between 5 and 10 days (8 days on average). Enteral nutrition with commercially available arginine-containing diet (Cubison) will start 20 hours post-surgery at an 8 ml/h flow rate; the rate will increase gradually, with the volume doubled every 24 hours, up to 100 ml/h and continued for six days. Simultaneously, commercially available two-chamber bags for peripheral access with composition identical to that used preoperatively will be administered via peripheral veins for five days.
Active Comparator: IV - Perioperative parenteral immunonutrition; Nutritional therapy of group IV will be based on intravenous preparations. Two-chamber bags with 480 kcal energetic value and 5.7 g of N in standard amino acids will be administered preoperatively. A solution of glutamine (Dipeptiven, 100 ml) and ω3-fatty acids (Omegaven, 100 ml) will be added to the bags. The duration of pre-operative preparatory phase ranged between 5 and 10 days (8 days on average). Enteral nutrition with elementary commercially available diet (Peptisorb) will be begun 20 hours post-surgery; it will be started at an 8 ml/h flow rate and increased gradually, with the volume doubled every 24 hours, up to 100 ml/h. The enteral nutrition will be continued for six days. During the initial five days post-surgery, the patients will be additionally supplemented parenterally via peripheral veins; similarly to the preoperative period, the content of two-chamber bag for peripheral access enriched with glutamine and ω3-fatty acids will be administered for five days.	Dietary supplement: Early postoperative enteral nutrition, based on standard elementary diet (Peptisorb); Early postoperative enteral nutrition with standard elementary diet (Peptisorb), will start 20 hours post-surgery. The initial flow rate will be 8 ml/h, which will increase gradually, with the volume doubled every 24 hours, up to 100 ml/h. The enteral nutrition wil be continued for six days. During the initial five days post-surgery, the patients will be additionally supplemented parenterally via peripheral veins (commercially available two-chamber bag for peripheral access with 480 kcal of energetic value and 5.7g of N contained in standard amino acids).; Drug: Perioperative parenteral immunonutrition (Dipeptiven, Omegaven); Nutritional therapy of group IV will based on intravenous preparations. Two-chamber bags with 480 kcal energetic value and 5.7 g of N in standard amino acids were administered preoperatively. A solution of glutamine (Dipeptiven, 100 ml) and ω3-fatty acids (Omegaven, 100 ml) will be added to the bags. The duration of pre-operative preparatory phase ranged between 5 and 10 days (8 days on average). Enteral nutrition with elementary commercially available diet (Peptisorb) will be begun 20 hours post-surgery; it will start at an 8 ml/h flow rate and increased gradually, with the volume doubled every 24 hours, up to 100 ml/h. The enteral nutrition was continued for six days. During the initial five days post-surgery, the patients will be additionally supplemented parenterally via peripheral veins; similarly to the preoperative period, the content of two-chamber bag for peripheral access enriched with glutamine and ω3-fatty acids will be administered for five days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phagocytic activity of blood platelets in gastric cancer patients.	Platelet count and phagocytic activity of thrombocytes will be examined twice in each patient. Blood samples for laboratory tests will be drawn prior to surgery and nutritional therapy and 12 days after the surgery. Thrombocyte count will be determined using ADVIA 120 haematological analyser. Phagocytic activity of blood platelets will be determined against Staphylococcus aureus ATCC 6538P bacterial strain. It expresses as the fraction of phagocytizing platelets and the phagocytic index. The fraction of phagocytizing platelets corresponds to the percentage of phagocyting thrombocytes per 1000 consecutive cells of this type. The phagocytic index represents the ratio of phagocytized bacteria per 100 phagocytic platelets.	Participants will be followed for the duration of hospital stay, an expected average of 3 weeks

Collaborators and Investigators

• Sponsor: Medical University of Bialystok
• Investigators: Principal Investigator: Zbigniew Kamocki, MD PhD, 2nd Department of General and Gastroenterological Surgery Medical University of Bialystok

Publications and helpful links

General Publications

• Noisakran S, Gibbons RV, Songprakhon P, Jairungsri A, Ajariyakhajorn Ch, Nisalak A, Jarman RG, Malasit P, Chokephaibulkit K, Perng GC. Detection of dengue virus in platelets isolated from dengue patients. Southeast Asian J Trop Med Public Health. 2009; 40: 253-262. Mustard JF, Packham MA. Platelet phagocytosis. Sem Haematol 1968; 2: 168-184. Clawson CC, White JG.: Platelet interaction with bacteria. I Reaction phases and effects on inhibitors. Am I Pathol 1971; 65: 367-380. Kemona H, Andrzejewska A, Prokopowicz J, Nowak H, Mantur M. Phagocytic activity of human blood platelets examined by electron microscopy. Folia Haematol Int Mag Klin Morphol Blutforsch 1986; 113: 696-702. Bessler H, Agam G, Diadetti M. Increased protein synthesis by human platelets during phagocytosis of latex particles in vivo. Thromb Diath Haemorrh 1976; 35: 350-357. Tang YQ, Yeaman MR, Selsted ME. Antimicrobial peptides from human platelets. Infect Immun 2002; 70: 6524-6533. Yeaman MR. The role of platelets in antimicrobial host defense. Clin Infect Dis 1997; 5: 951-968. Page CP. Platelets as inflammatory cells. Immunopharmacology 1989; 17: 51-59. Sun B, Li J, Kambayashi J. Interaction between GPIbalpha and FcgammaIIa receptor in human platelets. Biochem Biophys Res Commun 1999; 266: 24-27. Kemona H, Andrzejewska A, Prokopowicz J, Nowak H, Mantur M. Phagocytic activity of human blood platelets examined by electron microscopy. Folia Haematol 1986; 113: 696-702. Nash GF, Turner LF, Scully MF, Kakkar AK. Platelets and cancer. Lancet Oncol 2002; 3: 425-430. Yu Y, Zhou XD, Liu YK, Ren N, Chen J. Platelets promote the adhesion of human hepatoma cells with highly metastatic potential to extracellular matrix protein: involvement of platelets P-selectin and GP IIb-IIIa. J Cancer Res Clin Oncol 2002; 128: 283-287. Kamocki Z, Matowicka-Karna J, Piotrowski Z, Kemona H. Bacteriocidal capacity of platelets in gastric cancer patients. Neoplasma 2004; 51: 265-268
• Kamocki Z, Matowicka-Karna J, Gryko M, Zareba K, Kedra B, Kemona H. The effect of perioperative immunonutrition on the phagocytic activity of blood platelets in advanced gastric cancer patients. Clin Dev Immunol. 2013;2013:435672. doi: 10.1155/2013/435672. Epub 2013 Dec 1.

Study record dates

Study Major Dates

• Study Start: March 1, 2007
• Primary Completion (Anticipated): July 1, 2021
• Study Completion (Anticipated): October 1, 2022

Study Registration Dates

• First Submitted: September 26, 2012
• First Submitted That Met QC Criteria: October 10, 2012
• First Posted (Estimate): October 11, 2012

Study Record Updates

• Last Update Posted (Actual): March 17, 2020
• Last Update Submitted That Met QC Criteria: March 16, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: malnutrition,; perioperative artificial nutrition,; immunonutrition,; gastrectomy,; lymphocytes,; interleukin,; blood platelets,; phagocytic and bactericidal activity of blood platelets
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms
• Other Study ID Numbers: 3-37878 L