이 페이지는 자동 번역되었으며 번역의 정확성을 보장하지 않습니다. 참조하십시오 영문판 원본 텍스트의 경우.

Double Blinded Randomized Clinical Trial of the Effect of Open Versus Laparoscopic Colectomy on Neutrophils in Patients With Colon Cancer

2010년 3월 24일 업데이트: University Hospital Dubrava

The purpose of this study is:

  • to determine neutrophil activity in patients with colon cancer,
  • to determine levels sFas, sFasL and IL - 17 in serum of healthy volunteers and colon cancer patients and establish its prognostic value,
  • to elucidate the relationship between serum sFas, sFasL and IL - 17 levels and clinicopathologic features of colon cancer,
  • to compare the influence of laparoscopic and conventional procedures on postoperative serum sFas and sFasL levels in colon cancer patients
  • to compare the influence of laparoscopic and conventional procedures on postoperative serum IL - 17 levels in colon cancer patients
  • to compare the influence of laparoscopic and conventional procedures on postoperative neutrophil functions
  • to confirm the expression of FasL protein in human colorectal cancer and elucidate the relationship between FasL expression and clinicopathologic features of the disease, to establish the prevalence of Fas in primary colon adenocarcinomas and elucidate the relationship between FasL expression and clinicopathologic features of the disease
  • to determine the functional activity of tumour infiltrating neutrophils

연구 개요

상세 설명

Colorectal cancer is the leading cause of death worldwide. Tumour cell extravasation plays a key role in tumour metastasis. There are evidences tumour cell-leukocyte interactions may support tumour cell invasion and could create an optimal microenvironment for tumour growth at the metastatic site. Neutrophils produce free radicals and proteases; they could cause tumour cytolysis, as well as promote tumour growth and metastasis. It seems that neutrophils play an important role in the context of tumour and angiogenesis.

It is not well understood why FasL induces immune privilege in some organs but elicits inflammation. To explain these apparently conflicting phenomena, it is important to investigate the mechanism of FasL-induced inflammation in detail. Fas/FasL can serve as potential targets for effective antitumor therapy. This research will be useful to eludicate the importance of neutrophil in colorectal cancer. We will investigate the possible role of neutrophil activity and FasL-induced neutrophil infiltration on tumor growth in colorectal cancer. sFas and sFasL could be a way to measure the balance of apoptotic and immunoescape effect after surgical resection of colon cancer.

If the number of neutrophils in peripheral blood mirrors the situation in the tumor tissue, these data could support the investigation of neutrophil-targeted therapies in anti-cancer strategy.

Inflammation-dependent angiogenesis seems to be a central force in tumor growth and expansion, a concept supported by the observation that the use of anti-inflammatory drugs, leads to angiogenesis inhibition. The mechanisms of inflammatory angiogenesis could provide new approaches to target, cure, or prevent tumor angiogenesis. Investigation of the physiologic regulation of IL-17 may thus be useful for the treatment in clinical settings characterized by persistent neovascularisation.

Inhibition of neutrophil elastase might not only reduce the inflammatory response, but could also prevent cancer cell progression. Anti-neutrophil elastase therapy after tumour resection might be an important strategic approach for managing postoperative complications and preventing cancer recurrence.

Patients will be allocated to laparoscopic or conventional open colorectal surgery after eligibility had been confirmed and informed consent given. Randomization will be performed by computer; sequencing was based on a list of variable block sizes for a single centre without further stratification. The randomization list and opaque envelopes will be generated by independent personnel not otherwise involved in the trial. Information on the operation will be remain in consecutively numbered and sealed envelopes that will be stored in a specific box at the clinical site. The envelope containing the allocation will be added to a patient's file shortly before he or she enter the operating theatre. The envelope will be then open and the surgeon will perform the assigned procedure. Until the day of discharge of participants, nurses and other medical staff will be blinded for the type of surgery performed in patients with colorectal cancer by applying a covering abdominal bandage.

During the trial, all blood samples will be retrieved and assessed by a cytologist and molecular biologist blinded to the study arms.

연구 유형

중재적

등록 (예상)

60

단계

  • 해당 없음

연락처 및 위치

이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.

연구 장소

      • Zagreb, 크로아티아, 10 000
        • 모병
        • University Hospital "Dubrava"
        • 연락하다:
          • Igor Stipancic, MD, PhD, Professor
          • 전화번호: +3851290 2517
          • 이메일: igors@kbd.hr
        • 연락하다:
          • Valentina Ratkajec, MD
          • 전화번호: +3851290 3612
          • 이메일: vratkajec@kbd.hr
        • 수석 연구원:
          • Valentina Ratkajec, MD
        • 부수사관:
          • Igor Stipancic, MD, PhD, Professor

참여기준

연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.

자격 기준

공부할 수 있는 나이

20년 (성인, 고령자)

건강한 자원 봉사자를 받아들입니다

아니

연구 대상 성별

모두

설명

Inclusion Criteria:

All patients will be informed that additional blood and tissue samples will be taken during perioperative period for colon cancer research, and written consent will be obtained. Informed consent will be also obtained from each healthy volunteer.

Patients with the clinical diagnosis of colorectal cancer based on colonoscopy following histological confirmation will recruited. They should be suitable for elective surgical resection of the tumour along with lymph node dissection by right and left hemicolectomy, sigmoid colectomy, and anterior resection. Clinicopathologic characteristics of these patients will be investigated based on TNM classification of malignant tumours and modified Dukes classification Inclusion criteria; age between 18 and 80 years; colorectal cancer with single tumour locating at cecum, ascending colon, descending colon, sigmoid colon or recto sigmoid junction (distance from anal verge more than 15 cm); ASA I-III; and informed consent.

Exclusion criteria; patient refusal to participate in the prospective data collection; prior midline laparotomy; emergency surgery or urgent operation within 24 h after admission to the hospital; conversion to laparotomy; mechanic ileus; perforation or abscess with septic inflammatory response syndrome; planned stoma, low anterior resection or rectal extirpation; known immunological dysfunction (human immunodeficiency virus infection); presence of ongoing infection or infective chronic diseases; severe cardiovascular disease (New York Heart Association class higher than 3) or pulmonary insufficiency (severe pulmonary emphysema, interstitial pneumonitis, arterial PO2<79 mmHg); advanced liver disease (Child-Pugh class C); synchronous or metachronous (within five years) malignancy; pregnant or lactating women; continuous systemic steroid therapy; drug addiction; previous chemotherapy, radiotherapy or immune therapy.

공부 계획

이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.

연구는 어떻게 설계됩니까?

디자인 세부사항

  • 주 목적: 치료
  • 할당: 무작위
  • 중재 모델: 병렬 할당
  • 마스킹: 더블

무기와 개입

참가자 그룹 / 팔
개입 / 치료
활성 비교기: ARM I - Open colorectal surgery
Open colorectal surgery
Patients with colorectal cancer undergo open laparotomy and colorectal resection
다른 이름들:
  • Open colorectal surgery
실험적: ARM II - Laparoscopic colorectal surgery
Laparoscopic colorectal surgery
Patients with colorectal cancer undergo laparoscopic colorectal resection
다른: Control - reference value
Blood samples from healthy volunteers will be obtained at one time point.Peripheral blood samples will be obtained into tubes with no additive (BD Vacutainer System, Plymouth, UK).Samples will be processed to serum. Serum concentrations of sFas will be quantitative determinated by a sandwich enzyme immunoassay technique (ELISA)using specific anti-Fas MoAbs, Human sFas Immunoassay. Serum concentrations of sFasL will be quantitative determinated by a sandwich enzyme immunoassay technique (ELISA) using specific anti-Fasl MoAbs, Human sFas Immunoassay. Serum concentration of IL - 17 will be quantitative determinated by a sandwich enzyme immunoassay technique (ELISA) using Human IL-17 Immunoassay. . Peripheral blood samples for measurement of oxidative burst in neutrophils will be collected into heparinised blood tube. burst neutrophil production will be determined quantitatively by flow cytometry as described by Rothe using a commercial kit Bursttest Kit.
Informed consent will be obtained.Blood samples will be obtained at one time point. .Samples will be processed to serum, using a refrigerated centrifuge, then stored at -80C until analysis. Peripheral blood samples for measurement of oxidative burst in neutrophils will be collected into heparinised blood tube.Serum concentrations of sFas will be quantitative determinated by a sandwich enzyme immunoassay technique (ELISA) using specific anti-Fas MoAbs, Human sFas Immunoassay (Code: DFS00; QUANTIKINE R&D Systems Inc, Minneapolis, USA). Serum concentrations of sFasL will be quantitative determinated by a sandwich enzyme immunoassay technique (ELISA) using specific anti-Fasl MoAbs, Human sFas Immunoassay (Code: DFS00; QUANTIKINE R&D Systems Inc, Minneapolis, USA).Respiratory burst neutrophil production will be determined quantitatively by flow cytometry using a commercial kit Bursttest Kit (Cat. No: 10-0200; ORPEGEN Pharma, Germany)

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정
기간
Neutrophil activity before and after the open or laparoscopic surgery - Serum concentrations of sFas, sFasL and IL - 17.
기간: 24 hours before surgery, 72 hours after surgery
24 hours before surgery, 72 hours after surgery
Respiratory burst neutrophil production - Bursttest before and after open or laparoscopic surgery
기간: 24 hours before surgery and 2 hours after surgery
24 hours before surgery and 2 hours after surgery
Immunohistochemical detection of FasL in tumor and paratumor areas of colon cancer and normal colon mucosa taken at a distance of 10 cm from the tumor
기간: after surgery
after surgery
Immunohistochemical detection of Fas in tumor and paratumor areas of colon cancer and normal colon mucosa taken at a distance of 10 cm from the tumor
기간: after surgery
after surgery
Immunohistochemical detection of neutrophil elastase in tumor and paratumor areas of colon cancer and normal colon mucosa taken at a distance of 10 cm from the tumor
기간: after surgery
after surgery
Number of leukocytes, neutrophils, lymphocytes and neutrophils/lymphocytes ratio
기간: 24 hours before surgery, 2 hours after surgery, 72 hours after surgery
24 hours before surgery, 2 hours after surgery, 72 hours after surgery
CRP
기간: 24 hours before surgery, 72 hours after surgery
24 hours before surgery, 72 hours after surgery
Fe, transferrin, ferritin
기간: 24 hours before surgery, 72 hours after surgery
24 hours before surgery, 72 hours after surgery

2차 결과 측정

결과 측정
기간
to determine neutrophil activity in patients with colon cancer and healthy volunteers
기간: 24 hours before surgery, 2 hours and 72 hours after surgery
24 hours before surgery, 2 hours and 72 hours after surgery
to compare the influence of laparoscopic and conventional procedures on postoperative neutrophil function
기간: 24 hours before surgery, 2 hours and 72 hours after surgery
24 hours before surgery, 2 hours and 72 hours after surgery
to determine functional activity of tumour infiltrating neutrophils
기간: after surgery
after surgery
to determine an effect of surgery on neutrophil activity
기간: 24 hours before surgery, 2 hours and 72 hours after surgery
24 hours before surgery, 2 hours and 72 hours after surgery
to determine levels sFas, sFasL and IL - 17 in serum of healthy volunteers and colon cancer patients and establish its prognostic value
기간: 24 hours before surgery, 2 hours and 72 hours after surgery
24 hours before surgery, 2 hours and 72 hours after surgery
to eludicate the relationship between serum sFas, sFasL and IL - 17 levels and clinicopathologic features of colon cancer
기간: 24 hours before surgery, 2 hours and 72 hours after surgery
24 hours before surgery, 2 hours and 72 hours after surgery
to compare the influence of laparoscopic and conventional procedures on postoperative serum sFas, sFasL and IL - 17 levels in colon cancer patients
기간: 24 hours before surgery, 2 hours and 72 hours after surgery
24 hours before surgery, 2 hours and 72 hours after surgery
to confirm the expression of FasL protein in human colorectal cancer and elucidate the relationship between FasL expression and clinicopathologic features of the disease
기간: after surgery
after surgery
to establish the prevalence of Fas in primary colon adenocarcinomas and elucidate the relationship between Fas expression and clinicopathologic features of the disease
기간: after surgery
after surgery
loss of blood during the surgery, postoperative hospital stay, morbidity, and mortality within 30 days after surgery
기간: intraoperative and within 30 days after surgery
intraoperative and within 30 days after surgery

공동 작업자 및 조사자

여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

수사관

  • 연구 의자: Igor Stipančić, MD, PhD, Profssor, University Hospital Dubrava
  • 수석 연구원: Valentina Ratkajec, MD, University Hospital Dubrava

연구 기록 날짜

이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.

연구 주요 날짜

연구 시작

2008년 1월 1일

기본 완료 (실제)

2009년 7월 1일

연구 완료 (예상)

2010년 6월 1일

연구 등록 날짜

최초 제출

2009년 3월 10일

QC 기준을 충족하는 최초 제출

2009년 3월 11일

처음 게시됨 (추정)

2009년 3월 12일

연구 기록 업데이트

마지막 업데이트 게시됨 (추정)

2010년 3월 26일

QC 기준을 충족하는 마지막 업데이트 제출

2010년 3월 24일

마지막으로 확인됨

2010년 3월 1일

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이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .

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