Oxidative Stress and Inflammation Biomarkers in Surgically Treated Patients With Laryngeal Cancer

NCT05857202 | Unknown

• 1 other identifier: 754/5
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 2

Brief Summary

A experimental interventional prospective study will include patients with squamocellular carcinoma of the larynx surgically treated at the tertiary referral center. Clinical and demographic characteristics of the patients would be noted. The visual analog scale (VAS), Brief Pain Inventory questionnaire, Diagnosing Neuropathic Pain 4 (DN4) and Pain Detect Questionnaire were used for pain assessment. Questionnaire Quality of Life in Head and Neck Cancer Patients (QLQ - H\&N35) was used to assess the quality of life in patients with surgically treated laryngeal carcinoma. The type and consumption of analgesics used after surgery was monitored. The analgesics were used according to WHO Ladder. Blood samples ware taken from the patients for the analysis of oxidative stress parameters and inflammation parameters before the operative treatment and after the operative treatment (1-2 postoperative day and 9-10 postoperative day). The concentrations of interleukin 1 (IL-1) and 6 (IL-6), glutathione peroxidase 1 (GPX1), superoxide dismutase 1 (SOD1) and malondialdehyde (MDA) in the serum were determined. The aim of the study will be to assess concentrations of inflammatory biomarkers (IL-1, IL-6) and oxidative stress factors (MDA, SOD, GPKS1) in postoperative course in surgically treated patients with laryngeal carcinoma and in possible complication occurrence. Also, their correlation to type and dosage of used analgesics, to pain assessment questionnaire scores and QOL questionnaire scores in surgically treated patients with laryngeal carcinoma will be assessed.

Conditions

Oxidative Stress Induction; Laryngeal Cancer; Interleukins; Pain Management; Quality of Life; Pain, Postoperative

Keywords

oxidative stress; laryngeal cancer; pain management; interleukins

Outcome Measures

Primary Outcomes (6)

• Correlation between inflammatory marker IL-1 and pain intensity

  A positive correlation between concentration of inflammatory marker IL-1 and pain intensity (VAS score) in postoperatively in surgically treated patients with laryngeal cancer is expected. The concentrations of inflammatory parameters IL-1 (pg/mL) in the blood serum were determined by ELISA kits, according to the manufacturer's instructions. Pain intensity would be assessed using the visual analog scale (VAS). Scores were based on self-reported measures of pain severity recorded with a mark placed at one point along the length of a 10-cm line that represents a continuum between the two ends of the scale (0 mm on the left end of the scale marks ''no pain'' and 100mm on the right end of the scale marks ''the worst pain''). Correlation would be calculated with Spearman's rank correlation coefficient.

  7 days

• Correlation between inflammatory marker IL-6 and pain intensity

  A positive correlation between concentration of inflammatory marker IL-6 and pain intensity (VAS score) in postoperatively in surgically treated patients with laryngeal cancer is expected. The concentrations of inflammatory marker IL-6 (pg/mL) in the blood serum were determined by ELISA kits, according to the manufacturer's instructions. Pain intensity would be assessed using the visual analog scale (VAS). Scores were based on self-reported measures of pain severity recorded with a mark placed at one point along the length of a 10-cm line that represents a continuum between the two ends of the scale (0 mm on the left end of the scale marks ''no pain'' and 100mm on the right end of the scale marks ''the worst pain''). Correlation would be calculated with Spearman's rank correlation coefficient.

  7 days

• Correlation between inflammatory marker CRP and pain intensity

  A positive correlation between concentration of inflammatory marker CRP and pain intensity (VAS score) in postoperatively in surgically treated patients with laryngeal cancer is expected. The concentrations of inflammatory marker CRP (ng/mL) in the blood serum were determined by ELISA kits, according to the manufacturer's instructions. Pain intensity would be assessed using the visual analog scale (VAS). Scores were based on self-reported measures of pain severity recorded with a mark placed at one point along the length of a 10-cm line that represents a continuum between the two ends of the scale (0 mm on the left end of the scale marks ''no pain'' and 100mm on the right end of the scale marks ''the worst pain''). Correlation would be calculated with Spearman's rank correlation coefficient.

  7 days

• Correlation between oxidative stress marker MDA and pain intensity

  A positive correlation between concentration of oxidative stress marker MDA and pain intensity (VAS score) in postoperatively in surgically treated patients with laryngeal cancer is expected. The concentrations of oxidative stress marker MDA (ng/mL) in the blood serum were determined by ELISA kits, according to the manufacturer's instructions. Pain intensity would be assessed using the visual analog scale (VAS). Scores were based on self-reported measures of pain severity recorded with a mark placed at one point along the length of a 10-cm line that represents a continuum between the two ends of the scale (0 mm on the left end of the scale marks ''no pain'' and 100mm on the right end of the scale marks ''the worst pain''). Correlation would be calculated with Spearman's rank correlation coefficient.

  7 days

• Correlation between anti- oxidative stress marker SOD and pain intensity

  A negative correlation between concentration of anti-oxidative stress marker SOD and pain intensity (VAS score) in postoperatively in surgically treated patients with laryngeal cancer is expected. The concentrations of anti-oxidative stress marker SOD (pg/mL) in the blood serum were determined by ELISA kits, according to the manufacturer's instructions. Pain intensity would be assessed using the visual analog scale (VAS). Scores were based on self-reported measures of pain severity recorded with a mark placed at one point along the length of a 10-cm line that represents a continuum between the two ends of the scale (0 mm on the left end of the scale marks ''no pain'' and 100mm on the right end of the scale marks ''the worst pain''). Correlation would be calculated with Spearman's rank correlation coefficient.

  7 days

• Correlation between anti- oxidative stress marker GPX1 and pain intensity

  A negative correlation between concentration of anti- oxidative stress marker GPX1 and pain intensity (VAS score) in postoperatively in surgically treated patients with laryngeal cancer is expected. The concentrations of anti-oxidative stress marker GPX1 (pg/mL) in the blood serum were determined by ELISA kits, according to the manufacturer's instructions. Pain intensity would be assessed using the visual analog scale (VAS). Scores were based on self-reported measures of pain severity recorded with a mark placed at one point along the length of a 10-cm line that represents a continuum between the two ends of the scale (0 mm on the left end of the scale marks ''no pain'' and 100mm on the right end of the scale marks ''the worst pain''). Correlation would be calculated with Spearman's rank correlation coefficient.

  7 days

Study Arms (3)

Operated laryngeal cancer patients treated with non narcotic

Operated laryngeal cancer patients who were administered non narcotic drugs postoperative for pain management

Drug: Analgesics, Non-Narcotic

Operated laryngeal cancer patients treated with non narcotic and opioids

Operated laryngeal cancer patients who were administered non narcotic and opioids postoperative for pain management

Drug: Analgesics, Opioid; Drug: Analgesics, Non-Narcotic

Operated laryngeal cancer patients treated with opioids

Operated laryngeal cancer patients who were administered opioids postoperative for pain management

Drug: Analgesics, Opioid

Interventions

Analgesics, Opioid DRUG

Drugs were given immediately after the surgery, and correlation between analgesic use and parameters of oxidative stress and inflammation was assessed.

Operated laryngeal cancer patients treated with non narcotic and opioids; Operated laryngeal cancer patients treated with opioids

Analgesics, Non-Narcotic DRUG

Drugs were given immediately after the surgery, and correlation between analgesic use and parameters of oxidative stress and inflammation was assessed.

Operated laryngeal cancer patients treated with non narcotic; Operated laryngeal cancer patients treated with non narcotic and opioids

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study would include 100 patients with squamocellular carcinoma of the larynx surgically treated at the tertiary referral center. The diagnosis of laryngeal carcinoma was confirmed by otorhinolaryngological clinical examination, laryngomicroscopic examination with the biopsy and histopathologic examination. Additional diagnostics (chest radiography and computed tomography of the neck and ultrasonography of the abdomen) were performed to determine the TNM stage of the disease. The modality of surgical treatment was decided on the institutional Oncological Board and involved resection of the tumor (cordectomy, partial or total laryngectomy) with or without some form of the neck dissection in case of cervical lymphadenopathy.

You may qualify if:

• patients with all stages of diagnosed and operable laryngeal squamocellular carcinoma (T1-T4, N0-N2)

You may not qualify if:

• inoperable malignant disease
• presence of distant metastases
• previously treated malignancies
• presence of neurological or other severe comorbidities which prevent surgical treatment
• the presence of neurological or other severe physical and metabolic comorbidities
• substance abuse
• the inability to provide informed consent.

Sponsors & Collaborators

• Clinical Centre of Serbia: lead
• University of Belgrade: collaborator

Study Sites (2)

Clinic for otorhinolaryngology and maxillofacial surgery, Clinical Center of Serbia

Belgrade, 11000, Serbia

RECRUITING

Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade

Belgrade, 11000, Serbia

RECRUITING

Related Publications (13)

• Hinther A, Nakoneshny SC, Chandarana SP, Wayne Matthews T, Dort JC. Efficacy of postoperative pain management in head and neck cancer patients. J Otolaryngol Head Neck Surg. 2018 May 2;47(1):29. doi: 10.1186/s40463-018-0274-y.

  PMID: 29720267 BACKGROUND

• Sies H, Berndt C, Jones DP. Oxidative Stress. Annu Rev Biochem. 2017 Jun 20;86:715-748. doi: 10.1146/annurev-biochem-061516-045037. Epub 2017 Apr 24.

  PMID: 28441057 BACKGROUND

• Niklander SE, Murdoch C, Hunter KD. IL-1/IL-1R Signaling in Head and Neck Cancer. Front Oral Health. 2021 Aug 26;2:722676. doi: 10.3389/froh.2021.722676. eCollection 2021.

  PMID: 35048046 BACKGROUND

• Purdy M, Karkkainen J, Kokki M, Anttila M, Aspinen S, Juvonen P, Kokki H, Pulkki K, Rantanen T, Eskelinen M. Does Rectus Sheath Block Analgesia Alter Levels of the Oxidative Stress Biomarker Glutathione Peroxidase: A Randomised Trial of Patients with Cancer and Benign Disease. Anticancer Res. 2017 Feb;37(2):897-902. doi: 10.21873/anticanres.11396.

  PMID: 28179349 RESULT

• Salzman R, Kankova K, Pacal L, Tomandl J, Horakova Z, Kostrica R. Increased activity of superoxide dismutase in advanced stages of head and neck squamous cell carcinoma with locoregional metastases. Neoplasma. 2007;54(4):321-5.

  PMID: 17822322 RESULT

• Uz U, Eskiizmir G. Association Between Interleukin-6 and Head and Neck Squamous Cell Carcinoma: A Systematic Review. Clin Exp Otorhinolaryngol. 2021 Feb;14(1):50-60. doi: 10.21053/ceo.2019.00906. Epub 2021 Feb 1.

  PMID: 33587847 RESULT

• Rettig TC, Verwijmeren L, Dijkstra IM, Boerma D, van de Garde EM, Noordzij PG. Postoperative Interleukin-6 Level and Early Detection of Complications After Elective Major Abdominal Surgery. Ann Surg. 2016 Jun;263(6):1207-12. doi: 10.1097/SLA.0000000000001342.

  PMID: 26135695 RESULT

• Karkkainen J, Selander T, Purdy M, Juvonen P, Eskelinen M. Patients with Increased Levels of the Oxidative Stress Biomarker SOD1 Appear to Have Diminished Postoperative Pain After Midline Laparotomy: A Randomised Trial with Special Reference to Postoperative Pain Score (NRS). Anticancer Res. 2018 Feb;38(2):1003-1008. doi: 10.21873/anticanres.12315.

  PMID: 29374733 RESULT

• Liu Q, Xu K. Evaluation of some cellular biomarker proteins, oxidative stress and clinical indices as results of laparoscopic appendectomy for perforated appendicitis in children. Cell Mol Biol (Noisy-le-grand). 2020 Jun 5;66(3):197-203.

  PMID: 32538771 RESULT

• Si HB, Yang TM, Zeng Y, Zhou ZK, Pei FX, Lu YR, Cheng JQ, Shen B. Correlations between inflammatory cytokines, muscle damage markers and acute postoperative pain following primary total knee arthroplasty. BMC Musculoskelet Disord. 2017 Jun 17;18(1):265. doi: 10.1186/s12891-017-1597-y.

  PMID: 28623906 RESULT

• Xi MY, Li SS, Zhang C, Zhang L, Wang T, Yu C. Nalbuphine for Analgesia After Orthognathic Surgery and Its Effect on Postoperative Inflammatory and Oxidative Stress: A Randomized Double-Blind Controlled Trial. J Oral Maxillofac Surg. 2020 Apr;78(4):528-537. doi: 10.1016/j.joms.2019.10.017. Epub 2019 Nov 5.

  PMID: 31785250 RESULT

• Liu D, Liu H, Wu J, Gong B. Effects of Thoracic Paravertebral Blockon Inflammatory Response, Stress Response, Hemodynamics and Anesthesia Resuscitation inGallbladder Carcinoma. Cell Mol Biol (Noisy-le-grand). 2022 Feb 28;68(2):171-177. doi: 10.14715/cmb/2022.68.2.24.

  PMID: 35869710 RESULT

• Zivkovic A, Jotic A, Dozic I, Randjelovic S, Cirkovic I, Medic B, Milovanovic J, Trivic A, Korugic A, Vukasinovic I, Savic Vujovic K. Role of Oxidative Stress and Inflammation in Postoperative Complications and Quality of Life After Laryngeal Cancer Surgery. Cells. 2024 Nov 23;13(23):1951. doi: 10.3390/cells13231951.

  PMID: 39682700 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood samples that were taken from the patients for the analysis of oxidative stress (glutathione peroxidase 1, superoxide dismutase 1 and malondialdehyde) parameters and inflammation parameters (interleukin 1 and 6) before the operative treatment and after the operative treatment (1 postoperative day and 7 postoperative day).

MeSH Terms

Conditions

Laryngeal Neoplasms; Agnosia; Pain, Postoperative

Interventions

Analgesics, Opioid; Analgesics, Non-Narcotic

Condition Hierarchy (Ancestors)

Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Laryngeal Diseases; Respiratory Tract Diseases; Respiratory Tract Neoplasms; Otorhinolaryngologic Diseases; Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Postoperative Complications; Pathologic Processes; Pain

Intervention Hierarchy (Ancestors)

Narcotics; Central Nervous System Depressants; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Central Nervous System Agents; Therapeutic Uses

Study Officials

• Ana D Jotic, MD, PhD

  Clinic for otorhinolaryngology and maxillofacial surgery, Clinical center of Serbia

  STUDY DIRECTOR

• Katarina R Savic Vujovic, MD, PhD

  Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade

  STUDY DIRECTOR

Central Study Contacts

Ana D Jotic, MD, PHD

CONTACT

+381 63 7789825; anajotic@yahoo.com

Jovica M Milovanovic, MD, PhD

CONTACT

+381 63 7707374; jmtmilov@gmail.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant professor, MD, PhD

Study Record Dates

• First Submitted: March 29, 2023
• First Posted: May 12, 2023
• Study Start: September 1, 2022
• Primary Completion: September 1, 2023
• Study Completion: October 30, 2023
• Last Updated: May 12, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: 12 months after completion of the study
• Access Criteria: Interested investigators can access the data through available link

Locations

SE (2)